Datasets:

aisc-team-b1
/

guidelines

Dataset card Data Studio Files Files and versions Community

Split (1)

train · 38k rows

id stringlengths 40 40	source stringclasses 9 values	title stringlengths 2 345	clean_text stringlengths 35 1.63M	raw_text stringlengths 4 1.63M	url stringlengths 4 498
57d34b0b513f2191c83eeb9fc1ea1f03447ad860	wikidoc	Glycolic Acid	Glycolic Acid # Overview Glycolic acid (or hydroxyacetic acid); chemical formula C2H4O3 (also written as HOCH2COOH), is the smallest α-hydroxy acid (AHA). This colorless, odorless, and hygroscopic crystalline solid is highly soluble in water. It is used in various skin-care products. Glycolic acid is found in some sugar-crops. A glycolate is a salt or ester of glycolic acid. # Preparation There are multiple routes of synthesis of glycolic acid that are practiced today. The majority of the world's supply of glycolic acid is made in a catalyzed reaction of formaldehyde with synthesis gas (carbonylation of formaldehyde) is a particularly economical preparative route. It is also prepared by the reaction of chloroacetic acid with sodium hydroxide followed by re-acidification. In this way, a few million kilograms are produced annually. Other methods, not apparently in use, include hydrogenation of oxalic acid with nascent hydrogen and the hydrolysis of the cyanohydrin derived from formaldehyde. Some of today's glycolic acids are formic acid-free. Glycolic acid can be isolated from natural sources, such as sugarcane, sugar beets, pineapple, cantaloupe, and unripe grapes. Glycolic acid can also be prepared using an enzymatic biochemical process which produces fewer impurities compared to traditional chemical synthesis, requires less energy in production and produces less co-product. Each route can be evaluated for its relative costs and benefits. # Uses Glycolic acid is used in the textile industry as a dyeing and tanning agent, in food processing as a flavoring agent and as a preservative, and in the pharmaceutical industry as a skin care agent. It is also used in adhesives and plastics. Glycolic acid is often included into emulsion polymers, solvents and additives for ink and paint in order to improve flow properties and impart gloss. It is used in surface treatment products that increase the coefficient of friction on tile flooring. Due to its excellent capability to penetrate skin, glycolic acid finds applications in skin care products, most often as a chemical peel performed by a dermatologist, plastic surgeon or licensed aesthetician in concentrations of 20 to 70% or at-home kits in lower concentrations between 10 and 20%. In addition to concentration, pH also plays a large part in determining the potency of glycolic acid in solution. Physician-strength peels can have a pH as low as 0.6 (strong enough to completely keratolyze the epidermis), while acidities for home peels can be as high as 2.5. Glycolic acid is used to improve the skin's appearance and texture. It may reduce wrinkles, acne scarring, hyperpigmentation and improve many other skin conditions, including actinic keratosis, hyperkeratosis, and seborrheic keratosis. Once applied, glycolic acid reacts with the upper layer of the epidermis, weakening the binding properties of the lipids that hold the dead skin cells together. This allows the stratum corneum to be exfoliated, exposing live skin cells. Highly purified grades of glycolic acid are commercially available for personal care applications. Glycolic acid is also a useful intermediate for organic synthesis, in a range of reactions including: oxidation-reduction, esterification and long chain polymerization. It is used as a monomer in the preparation of polyglycolic acid and other biocompatible copolymers (e.g. PLGA). From the commercial perspective, important derivatives include the methyl (CAS# # Safety Glycolic acid is a strong irritant depending on the pH levels. Like ethylene glycol, it is metabolized to oxalic acid, which could make it dangerous if ingested.	Glycolic Acid Template:Chembox new Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview Glycolic acid (or hydroxyacetic acid); chemical formula C2H4O3 (also written as HOCH2COOH), is the smallest α-hydroxy acid (AHA). This colorless, odorless, and hygroscopic crystalline solid is highly soluble in water. It is used in various skin-care products. Glycolic acid is found in some sugar-crops. A glycolate is a salt or ester of glycolic acid. # Preparation There are multiple routes of synthesis of glycolic acid that are practiced today. The majority of the world's supply of glycolic acid is made in a catalyzed reaction of formaldehyde with synthesis gas (carbonylation of formaldehyde) is a particularly economical preparative route.[1] It is also prepared by the reaction of chloroacetic acid with sodium hydroxide followed by re-acidification. In this way, a few million kilograms are produced annually. Other methods, not apparently in use, include hydrogenation of oxalic acid with nascent hydrogen and the hydrolysis of the cyanohydrin derived from formaldehyde.[2] Some of today's glycolic acids are formic acid-free. Glycolic acid can be isolated from natural sources, such as sugarcane, sugar beets, pineapple, cantaloupe, and unripe grapes.[3] Glycolic acid can also be prepared using an enzymatic biochemical process which produces fewer impurities compared to traditional chemical synthesis, requires less energy in production and produces less co-product.[4] Each route can be evaluated for its relative costs and benefits. # Uses Glycolic acid is used in the textile industry as a dyeing and tanning agent,[5] in food processing as a flavoring agent and as a preservative, and in the pharmaceutical industry as a skin care agent. It is also used in adhesives and plastics.[6] Glycolic acid is often included into emulsion polymers, solvents and additives for ink and paint in order to improve flow properties and impart gloss. It is used in surface treatment products that increase the coefficient of friction on tile flooring. Due to its excellent capability to penetrate skin, glycolic acid finds applications in skin care products, most often as a chemical peel performed by a dermatologist, plastic surgeon or licensed aesthetician in concentrations of 20 to 70% or at-home kits in lower concentrations between 10 and 20%. In addition to concentration, pH also plays a large part in determining the potency of glycolic acid in solution. Physician-strength peels can have a pH as low as 0.6 (strong enough to completely keratolyze the epidermis), while acidities for home peels can be as high as 2.5. Glycolic acid is used to improve the skin's appearance and texture. It may reduce wrinkles, acne scarring, hyperpigmentation and improve many other skin conditions, including actinic keratosis, hyperkeratosis, and seborrheic keratosis[citation needed]. Once applied, glycolic acid reacts with the upper layer of the epidermis, weakening the binding properties of the lipids that hold the dead skin cells together. This allows the stratum corneum to be exfoliated, exposing live skin cells. Highly purified grades of glycolic acid are commercially available for personal care applications. Glycolic acid is also a useful intermediate for organic synthesis, in a range of reactions including: oxidation-reduction, esterification and long chain polymerization. It is used as a monomer in the preparation of polyglycolic acid and other biocompatible copolymers (e.g. PLGA). From the commercial perspective, important derivatives include the methyl (CAS#[96-35-5) and ethyl (CAS# 623-50-7) esters which are readily distillable (b.p. 147-9 and 158–159 °C, respectively), unlike the parent acid. The butyl ester (b.p. 178–186 °C) is a component of some varnishes, being desirable because it is nonvolatile and good dissolving properties.[2] # Safety Glycolic acid is a strong irritant depending on the pH levels.[7] Like ethylene glycol, it is metabolized to oxalic acid, which could make it dangerous if ingested.	https://www.wikidoc.org/index.php/Glycolic_Acid
8ff4a592d64555958136641dac3a944b1bd6c096	wikidoc	Glycolic acid	Glycolic acid # Overview Glycolic acid (or hydroxyacetic acid) is the smallest α-hydroxy acid (AHA). It appears in the form of a colorless, odorless and hydroscopic crystalline solid that is highly soluble in water and related solvents. Glycolic acid is associated with sugar-crops and is isolated from sugarcane, sugar beets, pineapple, canteloupe, and unripe grapes. # Uses Due to its excellent capability to penetrate skin, glycolic acid finds applications in skin care products, most often as a chemical peel performed by a dermatologist in concentrations of 20%-80% or at-home kits in lower concentrations of 10%. It is used to improve the skin's appearance and texture. It may reduce wrinkles, acne scarring, hyperpigmentation and improve many other skin conditions. Once applied, glycolic acid reacts with the upper layer of the epidermis, weakening the binding properties of the lipids that hold the dead skin cells together. This allows the outer skin to "dissolve" revealing the underlying skin. Glycolic acid is also a useful intermediate for organic synthesis, in a range of reactions including: oxidation-reduction, esterification and long chain polymerization. It is used as a monomer in the preparation of polyglycolic acid and other biocompatible copolymers (e.g. PLGA). Among other uses this compound finds employment in the textile industry as a dyeing and tanning agent, in food processing as a flavoring agent and as a preservative. Glycolic acid is often included into emulsion polymers, solvents and additives for ink and paint in order to improve flow properties and impart gloss. # Preparation Glycolic acid is isolated from natural sources and is inexpensively available. It can be prepared by the reaction of chloroacetic acid with sodium hydroxide followed by re-acidification. # Safety Glycolic acid is a mild irritant.	Glycolic acid Template:Chembox new # Overview Glycolic acid (or hydroxyacetic acid) is the smallest α-hydroxy acid (AHA). It appears in the form of a colorless, odorless and hydroscopic crystalline solid that is highly soluble in water and related solvents. Glycolic acid is associated with sugar-crops and is isolated from sugarcane, sugar beets, pineapple, canteloupe, and unripe grapes. # Uses Due to its excellent capability to penetrate skin, glycolic acid finds applications in skin care products, most often as a chemical peel performed by a dermatologist in concentrations of 20%-80% or at-home kits in lower concentrations of 10%. It is used to improve the skin's appearance and texture. It may reduce wrinkles, acne scarring, hyperpigmentation and improve many other skin conditions. Once applied, glycolic acid reacts with the upper layer of the epidermis, weakening the binding properties of the lipids that hold the dead skin cells together. This allows the outer skin to "dissolve" revealing the underlying skin. Glycolic acid is also a useful intermediate for organic synthesis, in a range of reactions including: oxidation-reduction, esterification and long chain polymerization. It is used as a monomer in the preparation of polyglycolic acid and other biocompatible copolymers (e.g. PLGA). Among other uses this compound finds employment in the textile industry as a dyeing and tanning agent, in food processing as a flavoring agent and as a preservative. Glycolic acid is often included into emulsion polymers, solvents and additives for ink and paint in order to improve flow properties and impart gloss. # Preparation Glycolic acid is isolated from natural sources and is inexpensively available. It can be prepared by the reaction of chloroacetic acid with sodium hydroxide followed by re-acidification. # Safety Glycolic acid is a mild irritant.[1]	https://www.wikidoc.org/index.php/Glycolic_acid
bf4a5a5d94ced15c4c85907934fef9dc1df03e51	wikidoc	Glycophorin A	Glycophorin A Glycophorin A (MNS blood group), also known as GYPA, is a protein which in humans is encoded by the GYPA gene. GYPA has also recently been designated CD235a (cluster of differentiation 235a). # Function Glycophorins A (GYPA; this protein) and B (GYPB) are major sialoglycoproteins of the human erythrocyte membrane which bear the antigenic determinants for the MN and Ss blood groups. In addition to the M or N and S or s antigens, that commonly occur in all populations, about 40 related variant phenotypes have been identified. These variants include all the variants of the Miltenberger complex and several isoforms of Sta; also, Dantu, Sat, He, Mg, and deletion variants Ena, S-s-U- and Mk. Most of the variants are the result of gene recombinations between GYPA and GYPB. # Genomics GypA, GypB and GypE are members of the same family and are located on the long arm of chromosome 4 (chromosome 4q31). The family evolved via two separate gene duplication events. The initial duplication gave rise to two genes one of subsequently evolved into GypA and the other which give rise via a second duplication event to GypB and GypE. These events appear to have occurred within a relatively short time span. The second duplication appears to have occurred via an unequal crossing over event. The GypA gene itself consists of 7 exons and has 97% sequence homology with GypB and GypE from the 5' untranslated transcription region (UTR) to the coding sequence encoding the first 45 amino acids. The exon at this point encodes the transmembrane domain. Within the intron downstream of this pint is an Alu repeat. The cross over event which created the genes ancestral to GypA and GypB/E occurred within this region. GypA can be found in all primates. GypB can be found only in gorillas and some of the higher primates suggesting that the duplication events occurred only recently. # Molecular biology There are about one million copies of this protein per erythrocyte. # Blood groups The MNS blood group was the second set of antigens discovered. M and N were identified in 1927 by Landsteiner and Levine. S and s in were described later in 1947. The frequencies of these antigens are - M: 78% Caucasoid; 74% Negroid - N: 72% Caucasoid; 75% Negroid - S: 55% Caucasoid; 31% Negroid - s: 89% Caucasoid; 93% Negroid # Molecular medicine ## Transfusion medicine The M and N antigens differ at two amino acid residues: the M allele has serine at position 1 (C at nucleotide 2) and glycine at position 5 (G at nucleotide 14) while the N allele has leucine at position 1 (T at nucleotide 2) and glutamate at position 5 (A at nucleotide 14). Both glycophorin A and B bind the Vicia graminea anti-N lectin. There are about 40 known variants in the MNS blood group system. These have arisen largely as a result of mutations within the 4 kb region coding for the extracellular domain. These include the antigens Mg, Dantu, Henshaw (He), Miltenberger, Nya, Osa, Orriss (Or), Raddon (FR) and Stones (Sta). Chimpanzees also have an MN blood antigen system. In chimpanzees M reacts strong but N only weakly. ## Null mutants In individuals who lack both glycophorin A and B the phenotype has been designated Mk. ## Dantu antigen The Dantu antigen was described in 1984. The Dantu antigen has an apparent molecular weight of 29 kiloDaltons (kDa) and 99 amino acids. The first 39 amino acids of the Dantu antigen are derived from glycophorin B and residues 40-99 are derived from glycophorin A. Dantu is associated with very weak s antigen, a protease-resistant N antigen and either very weak or no U antigen. There are at least three variants: MD, NE and Ph. The Dantu phenotype occurs with a frequency of Dantu phenotype is ~0.005 in American Blacks and < 0.001 in Germans. ## Henshaw antigen The Henshaw (He) antigen is due to a mutation of the N terminal region. There are three differences in the first three amino acid residues: the usual form has Tryptophan1-Serine-Threonine-Serine-Glycine5 while Henshaw has Leucine1-Serine-Threonine-Threonine-Glutamate5. This antigen is rare in Caucasians but occurs at a frequency of 2.1% in US and UK of African origin. It occurs at the rate of 7.0% in blacks in Natal and 2.7% in West Africans. At least 3 variants of this antigen have been identified. ## Miltenberger subsystem The Miltenberger (Mi) subsystem originally consisting of five phenotypes (Mia, Vw, Mur, Hil and Hut) now has 11 recognised phenotypes numbered I to XI (The antigen 'Mur' is named after to the patient the original serum was isolated from - a Mrs Murrel.) The name originally given to this complex refers to the reaction erythrocytes gave to the standard Miltenberger antisera used to test them. The subclasses were based on additional reactions with other standard antisera. Mi-I (Mia), Mi-II(Vw), Mi-VII and Mi-VIII are carried on glycophorin A. Mi-I is due to a mutation at amino acid 28 (threonine to methionine: C→T at nucleotide 83) resulting in a loss of the glycosylation at the asparagine26 residue. Mi-II is due to a mutation at amino acid 28 (threonine to lysine:C->A at nucleotide 83). Similar to the case of Mi-I this mutation results in a loss of the glycosylation at the asparagine26 residue. This alteration in glycoslation is detectable by the presence of a new 32kDa glycoprotein stainable with PAS. Mi-VII is due to a double mutation in glycophorin A converting an arginine residue into a threonine residue and a tyrosine residue into a serine at the positions 49 and 52 respectively. The threonine-49 residue is glycosylated. This appears to be the origin of one of the Mi-VII specific antigens (Anek) which is known to lie between residues 40-61 of glycophorin A and comprises sialic acid residue(s) attached to O-glycosidically linked oligosaccharide(s). This also explains the loss of a high frequency antigen ((EnaKT)) found in normal glycophorin A which is located within the residues 46-56. Mi-VIII is due to a mutation at amino acid residue 49 (arginine->threonine). M-VIII shares the Anek determinant with MiVII. Mi-III, Mi-VI and Mi-X are due to rearrangements of glycophorin A and B in the order GlyA (alpha)-GlyB (delta)-GlyA (alpha). Mil-IX in contrast is a reverse alpha-delta-alpha hybrid gene. Mi-V, MiV(J.L.) and Sta are due to unequal but homologous crossing-over between alpha and delta glycophorin genes. The MiV and MiV(J.L.) genes are arranged in the same 5' alpha-delta 3' frame whereas Sta gene is in a reciprocal 5'delta-alpha 3' configuration. The incidence of Mi-I in Thailand is 9.7%. Peptide constructs representative of Mia mutations MUT and MUR have been attached onto red blood cells (known as kodecytes) and are able to detect antibodies against these Miltenberger antigens Although uncommon in Caucasians (0.0098%) and Japanese (0.006%), the frequency of Mi-III is exceptionally high in several Taiwanese aboriginal tribes (up to 90%). In contrast its frequency is 2-3% in Han Taiwanese (Minnan). The Mi-III phenotype occurs in 6.28% of Hong Kong Chinese. Mi-IX (MNS32) occurs with a frequency of 0.43% in Denmark. ## Stone's antigen Stones (Sta) has been shown to be the product of a hybrid gene of which the 5'-half is derived from the glycophorin B whereas the 3'-half is derived from the glycophorin A. Several isoforms are known. This antigen is now considered to be part of the Miltenberger complex. ## Sat antigen A related antigen is Sat. This gene has six exons of which exon I to exon IV are identical to the N allele of glycophorin A whereas its 3' portion, including exon V and exon VI, are derived from the glycophorin B gene. The mature protein SAT protein contains 104 amino acid residues. ## Orriss antigen Orriss (Or) appears to be a mutant of glycophorin A but its precise nature has not yet been determined. ## Mg antigen The Mg antigen is carried on glycophorin A and lacks three O-glycolated side chains. ## Os antigen Osa (MNS38) is due to a mutation at nucleotide 273 (C->T) lying within exon 3 resulting in the replacement of a proline residue with a serine. ## Ny antigen Nya (MNS18) is due to a mutation at nucleotide 194 (T->A) which results in the substitution of an aspartate residue with a glutamate. ## Reactions Anti-M although occurring naturally has rarely been implicated in transfusion reactions. Anti-N is not considered to cause transfusion reactions. Severe reactions have been reported with anti-Miltenberger. Anti Mi-I (Vw) and Mi-III has been recognised as a cause of haemolytic disease of the newborn. Raddon has been associated with severe transfusion reactions. # Relevance for infection The Wright b antigen (Wrb) is located on glycophorin A and acts as a receptor for the malaria parasite Plasmodium falciparum. Cells lacking glycophorins A (Ena) are resistant to invasion by this parasite. The erythrocyte binding antigen 175 of P. falciparum recognises the terminal Neu5Ac(alpha 2-3)Gal-sequences of glycophorin A. Several viruses bind to glycophorin A including hepatitis A virus (via its capsid), bovine parvovirus , Sendai virus , influenza A and B , group C rotavirus , encephalomyocarditis virus and reovirus es.	Glycophorin A Glycophorin A (MNS blood group), also known as GYPA, is a protein which in humans is encoded by the GYPA gene.[1] GYPA has also recently been designated CD235a (cluster of differentiation 235a). # Function Glycophorins A (GYPA; this protein) and B (GYPB) are major sialoglycoproteins of the human erythrocyte membrane which bear the antigenic determinants for the MN and Ss blood groups. In addition to the M or N and S or s antigens, that commonly occur in all populations, about 40 related variant phenotypes have been identified. These variants include all the variants of the Miltenberger complex and several isoforms of Sta; also, Dantu, Sat, He, Mg, and deletion variants Ena, S-s-U- and Mk. Most of the variants are the result of gene recombinations between GYPA and GYPB.[1] # Genomics GypA, GypB and GypE are members of the same family and are located on the long arm of chromosome 4 (chromosome 4q31). The family evolved via two separate gene duplication events. The initial duplication gave rise to two genes one of subsequently evolved into GypA and the other which give rise via a second duplication event to GypB and GypE. These events appear to have occurred within a relatively short time span. The second duplication appears to have occurred via an unequal crossing over event. The GypA gene itself consists of 7 exons and has 97% sequence homology with GypB and GypE from the 5' untranslated transcription region (UTR) to the coding sequence encoding the first 45 amino acids. The exon at this point encodes the transmembrane domain. Within the intron downstream of this pint is an Alu repeat. The cross over event which created the genes ancestral to GypA and GypB/E occurred within this region. GypA can be found in all primates. GypB can be found only in gorillas and some of the higher primates suggesting that the duplication events occurred only recently. # Molecular biology There are about one million copies of this protein per erythrocyte. [Reference needed] # Blood groups The MNS blood group was the second set of antigens discovered. M and N were identified in 1927 by Landsteiner and Levine. S and s in were described later in 1947. The frequencies of these antigens are - M: 78% Caucasoid; 74% Negroid - N: 72% Caucasoid; 75% Negroid - S: 55% Caucasoid; 31% Negroid - s: 89% Caucasoid; 93% Negroid # Molecular medicine ## Transfusion medicine The M and N antigens differ at two amino acid residues: the M allele has serine at position 1 (C at nucleotide 2) and glycine at position 5 (G at nucleotide 14) while the N allele has leucine at position 1 (T at nucleotide 2) and glutamate at position 5 (A at nucleotide 14). Both glycophorin A and B bind the Vicia graminea anti-N lectin. There are about 40 known variants in the MNS blood group system. These have arisen largely as a result of mutations within the 4 kb region coding for the extracellular domain. These include the antigens Mg, Dantu, Henshaw (He), Miltenberger, Nya, Osa, Orriss (Or), Raddon (FR) and Stones (Sta). Chimpanzees also have an MN blood antigen system.[2] In chimpanzees M reacts strong but N only weakly. ## Null mutants In individuals who lack both glycophorin A and B the phenotype has been designated Mk.[3] ## Dantu antigen The Dantu antigen was described in 1984.[4] The Dantu antigen has an apparent molecular weight of 29 kiloDaltons (kDa) and 99 amino acids. The first 39 amino acids of the Dantu antigen are derived from glycophorin B and residues 40-99 are derived from glycophorin A. Dantu is associated with very weak s antigen, a protease-resistant N antigen and either very weak or no U antigen. There are at least three variants: MD, NE and Ph.[5] The Dantu phenotype occurs with a frequency of Dantu phenotype is ~0.005 in American Blacks and < 0.001 in Germans.[6] ## Henshaw antigen The Henshaw (He) antigen is due to a mutation of the N terminal region. There are three differences in the first three amino acid residues: the usual form has Tryptophan1-Serine-Threonine-Serine-Glycine5 while Henshaw has Leucine1-Serine-Threonine-Threonine-Glutamate5. This antigen is rare in Caucasians but occurs at a frequency of 2.1% in US and UK of African origin. It occurs at the rate of 7.0% in blacks in Natal[7] and 2.7% in West Africans.[8] At least 3 variants of this antigen have been identified. ## Miltenberger subsystem The Miltenberger (Mi) subsystem originally consisting of five phenotypes (Mia, Vw, Mur, Hil and Hut)[9] now has 11 recognised phenotypes numbered I to XI (The antigen 'Mur' is named after to the patient the original serum was isolated from - a Mrs Murrel.) The name originally given to this complex refers to the reaction erythrocytes gave to the standard Miltenberger antisera used to test them. The subclasses were based on additional reactions with other standard antisera. Mi-I (Mia), Mi-II(Vw), Mi-VII and Mi-VIII are carried on glycophorin A. Mi-I is due to a mutation at amino acid 28 (threonine to methionine: C→T at nucleotide 83) resulting in a loss of the glycosylation at the asparagine26 residue.[10][11] Mi-II is due to a mutation at amino acid 28 (threonine to lysine:C->A at nucleotide 83).[11] Similar to the case of Mi-I this mutation results in a loss of the glycosylation at the asparagine26 residue. This alteration in glycoslation is detectable by the presence of a new 32kDa glycoprotein stainable with PAS.[12] Mi-VII is due to a double mutation in glycophorin A converting an arginine residue into a threonine residue and a tyrosine residue into a serine at the positions 49 and 52 respectively.[13] The threonine-49 residue is glycosylated. This appears to be the origin of one of the Mi-VII specific antigens (Anek) which is known to lie between residues 40-61 of glycophorin A and comprises sialic acid residue(s) attached to O-glycosidically linked oligosaccharide(s). This also explains the loss of a high frequency antigen ((EnaKT)) found in normal glycophorin A which is located within the residues 46-56. Mi-VIII is due to a mutation at amino acid residue 49 (arginine->threonine).[14] M-VIII shares the Anek determinant with MiVII.[15] Mi-III, Mi-VI and Mi-X are due to rearrangements of glycophorin A and B in the order GlyA (alpha)-GlyB (delta)-GlyA (alpha).[16] Mil-IX in contrast is a reverse alpha-delta-alpha hybrid gene.[17] Mi-V, MiV(J.L.) and Sta are due to unequal but homologous crossing-over between alpha and delta glycophorin genes.[18] The MiV and MiV(J.L.) genes are arranged in the same 5' alpha-delta 3' frame whereas Sta gene is in a reciprocal 5'delta-alpha 3' configuration. The incidence of Mi-I in Thailand is 9.7%.[19] Peptide constructs representative of Mia mutations MUT and MUR have been attached onto red blood cells (known as kodecytes) and are able to detect antibodies against these Miltenberger antigens[20][21][22] Although uncommon in Caucasians (0.0098%) and Japanese (0.006%), the frequency of Mi-III is exceptionally high in several Taiwanese aboriginal tribes (up to 90%). In contrast its frequency is 2-3% in Han Taiwanese (Minnan). The Mi-III phenotype occurs in 6.28% of Hong Kong Chinese.[23] Mi-IX (MNS32) occurs with a frequency of 0.43% in Denmark.[24] ## Stone's antigen Stones (Sta) has been shown to be the product of a hybrid gene of which the 5'-half is derived from the glycophorin B whereas the 3'-half is derived from the glycophorin A. Several isoforms are known. This antigen is now considered to be part of the Miltenberger complex. ## Sat antigen A related antigen is Sat. This gene has six exons of which exon I to exon IV are identical to the N allele of glycophorin A whereas its 3' portion, including exon V and exon VI, are derived from the glycophorin B gene. The mature protein SAT protein contains 104 amino acid residues. ## Orriss antigen Orriss (Or) appears to be a mutant of glycophorin A but its precise nature has not yet been determined.[25] ## Mg antigen The Mg antigen is carried on glycophorin A and lacks three O-glycolated side chains.[26] ## Os antigen Osa (MNS38) is due to a mutation at nucleotide 273 (C->T) lying within exon 3 resulting in the replacement of a proline residue with a serine.[27] ## Ny antigen Nya (MNS18) is due to a mutation at nucleotide 194 (T->A) which results in the substitution of an aspartate residue with a glutamate.[27] ## Reactions Anti-M although occurring naturally has rarely been implicated in transfusion reactions. Anti-N is not considered to cause transfusion reactions. Severe reactions have been reported with anti-Miltenberger. Anti Mi-I (Vw) and Mi-III has been recognised as a cause of haemolytic disease of the newborn.[28] Raddon has been associated with severe transfusion reactions.[29] # Relevance for infection The Wright b antigen (Wrb) is located on glycophorin A and acts as a receptor for the malaria parasite Plasmodium falciparum.[30] Cells lacking glycophorins A (Ena) are resistant to invasion by this parasite.[31] The erythrocyte binding antigen 175 of P. falciparum recognises the terminal Neu5Ac(alpha 2-3)Gal-sequences of glycophorin A.[32] Several viruses bind to glycophorin A including hepatitis A virus (via its capsid),[33] bovine parvovirus ,[34] Sendai virus ,[35] influenza A and B ,[36] group C rotavirus ,[37] encephalomyocarditis virus [38] and reovirus es.[39]	https://www.wikidoc.org/index.php/Glycophorin_A
d7b5d38a95c7265317e2a29e897ce7d8e29de546	wikidoc	Glycylcycline	Glycylcycline Glycylcyclines are a new class of antibiotics derived from tetracycline. These tetracycline analogues are specifically designed to overcome two common mechanisms of tetracycline resistance, namely resistance mediated by acquired efflux pumps and/or ribosomal protection. Presently, there is only one glycylcycline antibiotic for clinical use: tigecycline. # History The development of these agents was spurred by the increasing prevalence of bacteria resistant to tetracyclines. These agents were first synthesized in the early 1990's by making modifications to the tetracyclines. By adding a bulky N,N-dimethylglycylamido side chain to position 9 of minocycline, the compound became less susceptible to tetracycline resistance mediated by acquired efflux pumps and/or ribosomal protection. Further development of this initial work led to the creation of tigecycline, the first glycylcycline available for clinical use. # Mechanism of Action Glycylcycline antibiotics have a similar mechanism of action as tetracycline antibiotics. Both classes of antibiotics bind to the 30S ribosomal subunit to prevent the amino-acyl tRNA from binding to the A site of the ribosome. However, the glycylcyclines appear to bind more effectively than the tetracyclines . # Mechanisms of Resistance While glycylcyclines have greater efficacy against organisms with tetracycline resistance mediated by acquired efflux pumps and/or ribosomal protection, the glycylcyclines are not effective against organisms with chromosomal efflux pumps, such as Pseudomonas and Proteeae. # Side Effects and Contraindications Since glycylcyclines are similar to tetracyclines, they share many of the same side effects and contraindications as tetracyclines. These side effects may include nausea/vomiting, headache, photosensitivity, discoloration of growing teeth, and fetal damage. These antibiotics should not be given to pregnant women due to risk of fetal harm. Additionally, these drugs should not be administered during periods of tooth development because of the risk of tooth discoloration. Due to glycylcyclines' similarities with tetracyclines, hypersensitivity reactions to tetracycline antibiotics may predispose one to hypersensitivity reactions with glycylcycline antibiotics; hence, glycylcyclines should be used with caution in these patients.	Glycylcycline Glycylcyclines are a new class of antibiotics derived from tetracycline. These tetracycline analogues are specifically designed to overcome two common mechanisms of tetracycline resistance, namely resistance mediated by acquired efflux pumps and/or ribosomal protection. Presently, there is only one glycylcycline antibiotic for clinical use: tigecycline. # History The development of these agents was spurred by the increasing prevalence of bacteria resistant to tetracyclines. These agents were first synthesized in the early 1990's by making modifications to the tetracyclines. By adding a bulky N,N-dimethylglycylamido side chain to position 9 of minocycline, the compound became less susceptible to tetracycline resistance mediated by acquired efflux pumps and/or ribosomal protection. Further development of this initial work led to the creation of tigecycline, the first glycylcycline available for clinical use. # Mechanism of Action Glycylcycline antibiotics have a similar mechanism of action as tetracycline antibiotics. Both classes of antibiotics bind to the 30S ribosomal subunit to prevent the amino-acyl tRNA from binding to the A site of the ribosome. However, the glycylcyclines appear to bind more effectively than the tetracyclines [1]. # Mechanisms of Resistance While glycylcyclines have greater efficacy against organisms with tetracycline resistance mediated by acquired efflux pumps and/or ribosomal protection, the glycylcyclines are not effective against organisms with chromosomal efflux pumps, such as Pseudomonas and Proteeae[2]. # Side Effects and Contraindications Since glycylcyclines are similar to tetracyclines, they share many of the same side effects and contraindications as tetracyclines. These side effects may include nausea/vomiting, headache, photosensitivity, discoloration of growing teeth, and fetal damage. These antibiotics should not be given to pregnant women due to risk of fetal harm. Additionally, these drugs should not be administered during periods of tooth development because of the risk of tooth discoloration. Due to glycylcyclines' similarities with tetracyclines, hypersensitivity reactions to tetracycline antibiotics may predispose one to hypersensitivity reactions with glycylcycline antibiotics; hence, glycylcyclines should be used with caution in these patients.	https://www.wikidoc.org/index.php/Glycylcycline
81a205a8b910129a5dce329553ee03bf8dfc81d8	wikidoc	Visceroptosis	Visceroptosis Synonyms and keywords:splanchnoptosis, abdominal ptosis, Glénard's disease # Overview Visceroptosis (or enteroptosis) is a prolapse or a sinking of the abdominal viscera below their natural position. Any or all of the organs may be displaced downward. When the intestines are involved, the condition is known as enteroptosis; when the stomach is found below its normal position, the term gastroptosis is used. The disease exists in all degrees of severity and may give rise to no symptoms whatsoever. Generally, however, there is loss of appetite, nervous dyspepsia, constipation, or diarrhea, abdominal distention, headache, vertigo, emaciation, and loss of sleep. Any or all of these symptoms may be present. The condition is brought about by loss of muscular tone, particularly of the abdominal muscles, intestinal autointoxication, with relaxation of the ligaments which hold the viscera in place. In women, tight lacing has been held to be a frequent cause. The symptoms may be alleviated by supporting the organs with a properly applied bandage, or other similar device. Rest in bed, attention to diet, hygiene, exercise, and general muscular up building will cure the majority of cases. In others operation may become necessary. - Dr. Frantz Glénard (1848-1920) Visceroptosis is also called splanchnoptosis, abdominal ptosis, and Glénard's disease, after a French physician Frantz Glénard (1848-1920). - Glénard's test — The examiner, standing behind the patient, places his arms around the patient, so that his hands meet in front of the patient's abdomen; he squeezes and raises the viscera and then allows them to fall suddenly. If the patient feels relieved by the raising pressure and experiences distress on the release, the condition is probably one of splanchoptosis. Also called girdle test. - Glénard's theory — The theory that abdominal ptosis is a nutritional disease with atrophy and prolapse of the intestine. - Stiller's theory — The theory that gastroptosis is due to universal asthenia characterized by weakness and laxity of the viscera. # Historical Perspective # Classification # Pathophysiology # Causes # Differentiating Visceroptosis from other Diseases # Epidemiology and Demographics # Risk Factors # Screening # Natural History, Complications and Prognosis ## Natural History ## Complications ## Prognosis # Diagnosis ## Diagnostic Criteria ## History and Symptoms ## Physical Examination ## Laboratory Findings ## Imaging Findings ## Other Diagnostic Studies # Treatment ## Medical Therapy ## Surgery ## Prevention	Visceroptosis Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Synonyms and keywords:splanchnoptosis, abdominal ptosis, Glénard's disease # Overview Template:Search infobox Visceroptosis (or enteroptosis) is a prolapse or a sinking of the abdominal viscera below their natural position. Any or all of the organs may be displaced downward. When the intestines are involved, the condition is known as enteroptosis; when the stomach is found below its normal position, the term gastroptosis is used. The disease exists in all degrees of severity and may give rise to no symptoms whatsoever. Generally, however, there is loss of appetite, nervous dyspepsia, constipation, or diarrhea, abdominal distention, headache, vertigo, emaciation, and loss of sleep. Any or all of these symptoms may be present. The condition is brought about by loss of muscular tone, particularly of the abdominal muscles, intestinal autointoxication, with relaxation of the ligaments which hold the viscera in place. In women, tight lacing has been held to be a frequent cause. The symptoms may be alleviated by supporting the organs with a properly applied bandage, or other similar device. Rest in bed, attention to diet, hygiene, exercise, and general muscular up building will cure the majority of cases. In others operation may become necessary. - Dr. Frantz Glénard (1848-1920) Visceroptosis is also called splanchnoptosis, abdominal ptosis, and Glénard's disease, after a French physician Frantz Glénard (1848-1920). - Glénard's test — The examiner, standing behind the patient, places his arms around the patient, so that his hands meet in front of the patient's abdomen; he squeezes and raises the viscera and then allows them to fall suddenly. If the patient feels relieved by the raising pressure and experiences distress on the release, the condition is probably one of splanchoptosis.[1] Also called girdle test. - Glénard's theory — The theory that abdominal ptosis is a nutritional disease with atrophy and prolapse of the intestine. - Stiller's theory — The theory that gastroptosis is due to universal asthenia characterized by weakness and laxity of the viscera. # Historical Perspective # Classification # Pathophysiology # Causes # Differentiating Visceroptosis from other Diseases # Epidemiology and Demographics # Risk Factors # Screening # Natural History, Complications and Prognosis ## Natural History ## Complications ## Prognosis # Diagnosis ## Diagnostic Criteria ## History and Symptoms ## Physical Examination ## Laboratory Findings ## Imaging Findings ## Other Diagnostic Studies # Treatment ## Medical Therapy ## Surgery ## Prevention # External links - The Visceroptosis Webpage©	https://www.wikidoc.org/index.php/Gl%C3%A9nard%27s_disease
1a1b86a5f29159ca8e2ab6ba20f80ad0c04e5878	wikidoc	Gnathostomata	Gnathostomata Gnathostomata is the group of vertebrates with jaws. The group is traditionally a superclass, including the familiar classes of fish, birds, mammals, reptiles, and amphibians, and a sister group of the jawless vertebrates Agnatha. However, recent genetic studies are causing a reassessment of Gnathostomata as a grouping. New fossil founds suggests thelodonts as the closest relatives of the Gnathostomata. It is believed that the jaws evolved from anterior gill support arches that had acquired a new role, being modified to pump water over the gills by opening and closing the mouth more effectively - the buccal pump mechanism. The mouth could then grow bigger and wider, making it possible to capture larger prey. This close and open mechanism would with time become stronger and tougher, being transformed into real jaws. Placoderms used sharp bony plates as teeth instead, and newer research indicates the jaws in placoderms evolved independently of the rest of the remaining gnathostomates. Other distinguishing characteristics of living gnathostomates are the myelin sheathes of neurons, and an adaptive immune system. The Gnathostomata first appeared in the Ordovician period and became common in the Devonian period. # Taxonomy and phylogeny	Gnathostomata Template:Expand Gnathostomata is the group of vertebrates with jaws. The group is traditionally a superclass, including the familiar classes of fish, birds, mammals, reptiles, and amphibians, and a sister group of the jawless vertebrates Agnatha. However, recent genetic studies are causing a reassessment of Gnathostomata as a grouping. New fossil founds suggests thelodonts as the closest relatives of the Gnathostomata.[1] It is believed that the jaws evolved from anterior gill support arches that had acquired a new role, being modified to pump water over the gills by opening and closing the mouth more effectively - the buccal pump mechanism. The mouth could then grow bigger and wider, making it possible to capture larger prey. This close and open mechanism would with time become stronger and tougher, being transformed into real jaws. Placoderms used sharp bony plates as teeth instead, and newer research indicates the jaws in placoderms evolved independently of the rest of the remaining gnathostomates.[2] Other distinguishing characteristics of living gnathostomates are the myelin sheathes of neurons, and an adaptive immune system. The Gnathostomata first appeared in the Ordovician period and became common in the Devonian period. # Taxonomy and phylogeny	https://www.wikidoc.org/index.php/Gnathostomata
284292c1c8a80c24c2c86c5ef01a914f302b9671	wikidoc	Gordon Zubrod	Gordon Zubrod # Overview Dr Charles Gordon Zubrod (1914-January 19 1999) was an American oncologist who played a prominent role in the introduction of chemotherapy for cancer. He was one of the recipients of the 1972 Albert Lasker Awards in recognition of his contributions to the field, amongst many other doctorates and awards. # Life and work Dr. Zubrod, an alumnus of the Georgetown Preparatory School (class of 1932) and Columbia University College of Physicians and Surgeons (1940 class), served in the U.S. army medical corps during World War II, where he worked on a replacement for quinine in the treatment of malaria. The unit eventually discovered chloroquine. In 1946 he commenced work at Johns Hopkins University Medical School, and was appointed assistant professor of medicine and director of research at Saint Louis University in 1953. This position lasted briefly: he became clinical director of the National Institutes of Health in 1954 and became head of the Division of Cancer Treatment of the National Cancer Institute in 1956 and scientific director in 1961. Here, he put an emphasis on the development of new chemotherapy agents and their use in clinical trials. He is credited with the introduction of the platinum-containing compounds (e.g. cisplatin). Several other new classes of chemotherapeutics were identified under Zubrod's leadership. Dr. Zubrod's name is also connected to a widely used assessment scale for performance of cancer patients, the Performance Status of the Eastern Cooperative Oncology Group (ECOG) for Patients with Cancer (Zubrod scale). Zubrod left the NCI in 1974, and became a professor and chair of the department of oncology at the University of Miami School of Medicine (now the Leonard M. Miller School of Medicine) and served at the director of the Florida Comprehensive Cancer Center. He retired from this position in 1990.	Gordon Zubrod # Overview Dr Charles Gordon Zubrod (1914-January 19 1999) was an American oncologist who played a prominent role in the introduction of chemotherapy for cancer. He was one of the recipients of the 1972 Albert Lasker Awards in recognition of his contributions to the field, amongst many other doctorates and awards. # Life and work Dr. Zubrod, an alumnus of the Georgetown Preparatory School (class of 1932) and Columbia University College of Physicians and Surgeons (1940 class), served in the U.S. army medical corps during World War II, where he worked on a replacement for quinine in the treatment of malaria. The unit eventually discovered chloroquine. In 1946 he commenced work at Johns Hopkins University Medical School, and was appointed assistant professor of medicine and director of research at Saint Louis University in 1953. This position lasted briefly: he became clinical director of the National Institutes of Health in 1954 and became head of the Division of Cancer Treatment of the National Cancer Institute in 1956 and scientific director in 1961. Here, he put an emphasis on the development of new chemotherapy agents and their use in clinical trials. He is credited with the introduction of the platinum-containing compounds (e.g. cisplatin). Several other new classes of chemotherapeutics were identified under Zubrod's leadership. Dr. Zubrod's name is also connected to a widely used assessment scale for performance of cancer patients, the Performance Status of the Eastern Cooperative Oncology Group (ECOG) for Patients with Cancer (Zubrod scale). Zubrod left the NCI in 1974, and became a professor and chair of the department of oncology at the University of Miami School of Medicine (now the Leonard M. Miller School of Medicine) and served at the director of the Florida Comprehensive Cancer Center. He retired from this position in 1990.	https://www.wikidoc.org/index.php/Gordon_Zubrod
958eec27b3cd821274e4210e64a71f0e55fd76fa	wikidoc	Gout	Gout overview # Overview Gout is a common arthritis caused by deposition of monosodium urate crystals within joints after chronic hyperuricaemia. It affects 1-2% of adults in developed countries, where it is the most common inflammatory arthritis in men. Epidemiological data are consistent with a rise in prevalence of gout. Diet and genetic polymorphisms of renal transporters of urate seem to be the main causal factors of primary gout. Gout and hyperuricaemia are associated with hypertension, diabetes mellitus, metabolic syndrome, and renal and cardiovascular diseases. Non-steroidal anti-inflammatory drugs and colchicine remain the most widely recommended drugs to treat acute attacks. Oral corticosteroids could be an alternative to these drugs. Interleukin 1beta is a pivotal mediator of acute gout and could become a therapeutic target. When serum uric acid concentrations are lowered below monosodium urate saturation point, the crystals dissolve and gout can be cured. Patient education, appropriate lifestyle advice, and treatment of comorbidities are an important part of management of patients with gout. Gout, otherwise called as metabolic arthritis is a congenital disorder of Uric acid metabolism. In this condition, monosodium urate or uric acid crystals are deposited on the articular cartilage of joints, tendons and surrounding tissues due to elevated concentrations of uric acid in the blood stream. This provokes an inflammatory reaction of these tissues. These deposits often increase in size and burst through the skin to form sinuses discharging a chalky white material. ## Gout historical perspective - Gout was first described by Egyptians in 2640 BC. - Hippocrates described podagra in 5th century BC as the unwalkable disease. - Galen described the monosodium urate crystal deposition following long standing hyperuricemia as Tophi. He described gout as a discharge of the four humors of the body in unbalanced amounts into the joints. - The word Gout was first used in 1200s AD by Dominican monk Randolphus of Bocking and was derived from the Latin word 'Gutta'. - Aulus Cornelius Celsus discovered many symptoms of gout. ## Pathophysiology Gout occurs when mono-sodium urate crystals form on the articular cartilage of joints, on tendons, and in the surrounding tissues. Purine metabolism gives rise to uric acid, which is normally excreted in the urine. Defects in the kidney may cause uric acid to build up in the blood, leading to hyperuricemia, and the subsequent formation of gout crystals. ## Differentiating Gout from other Diseases Gout needs to be differentiated from other diseases such as cellulitis, rheumatoid arthritis, septic arthritis and sarcoidosis as they present with similar symptoms. ## Epidemiology and Demographics Gout affects men in age group 40-50 years. It is more common in people from the Pacific Islands, and New Zealand. In the United States, gout is twice as prevalent in African American males as it is in Caucasians. ## Risk Factors Several factors may put a person at risk for developing gout. These include the presence of; hypertension, diabetes, hypercholesterolemia, obesity, and alcohol abuse. Certain medications may also put a person at a higher risk for developing gout. ## Prognosis The prognosis of gout is good if it is treated early, and if the person maintains a healthy lifestyle with modification of their individual risk factors. # Diagnosis ## Symptoms The classic picture of an acute gouty attack, is sudden, excruciating, unexpected and burning pain. There will also be swelling, redness, warmth, and stiffness in the joint. In approximately 75% of first episodes, gout usually attacks the big toe. ## Laboratory Findings A definitive diagnosis of gout is made from light microscopy of the fluid aspirated from the joint. The fluid demonstrates intracellular negatively bi-refringent monosodium urate crystals and polymorphonuclear leukocytes in the synovial fluid. Although hyperuricemia is a common feature of gout, a high uric acid level does not necessarily mean a person will develop gout. ## X-ray An x-ray is done when gout is suspected to rule out other abnormalities of the bone that may be causing the pain. Most commonly in gout, the x-ray will show no abnormalities, or a small amount of soft tissue swelling. # Treatment ## Medical Therapy The first goal of therapy when treating gout, is pain relief. This can be acheived with NSAIDs, and oral or intra-articular glucocorticoids. If colchicine is given, it should be taken within the first 12 hours of the attack. Other, less standard methods of treatment include the use of hemorrhoidal ointment, ice, increasing mobility, and acetazolamide. ## Surgery For extreme cases of gout, surgery may be necessary to remove large tophi and correct joint deformity. ## Secondary Prevention There are several methods used to prevent a re-occurrence of gout. Dietary changes include reducing the intake of foods that increase the levels of purine in blood, such as protein and alcohol. Several foods, and vitamin C have been thought to decrease the levels of purine in the blood. Modification of the risk factors for gout has been shown to also be beneficial in reducing the reoccurrence of gout. There are medications which can increase the excretion of uric acid, and reduce uric acid levels through other mechanisms.	Gout overview Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Shivam Singla, M.D.[2] # Overview Gout is a common arthritis caused by deposition of monosodium urate crystals within joints after chronic hyperuricaemia. It affects 1-2% of adults in developed countries, where it is the most common inflammatory arthritis in men. Epidemiological data are consistent with a rise in prevalence of gout. Diet and genetic polymorphisms of renal transporters of urate seem to be the main causal factors of primary gout. Gout and hyperuricaemia are associated with hypertension, diabetes mellitus, metabolic syndrome, and renal and cardiovascular diseases. Non-steroidal anti-inflammatory drugs and colchicine remain the most widely recommended drugs to treat acute attacks. Oral corticosteroids could be an alternative to these drugs. Interleukin 1beta is a pivotal mediator of acute gout and could become a therapeutic target. When serum uric acid concentrations are lowered below monosodium urate saturation point, the crystals dissolve and gout can be cured. Patient education, appropriate lifestyle advice, and treatment of comorbidities are an important part of management of patients with gout. Gout, otherwise called as metabolic arthritis is a congenital disorder of Uric acid metabolism. In this condition, monosodium urate or uric acid crystals are deposited on the articular cartilage of joints, tendons and surrounding tissues due to elevated concentrations of uric acid in the blood stream. This provokes an inflammatory reaction of these tissues. These deposits often increase in size and burst through the skin to form sinuses discharging a chalky white material. ## Gout historical perspective - Gout was first described by Egyptians in 2640 BC. - Hippocrates described podagra in 5th century BC as the unwalkable disease. - Galen described the monosodium urate crystal deposition following long standing hyperuricemia as Tophi. He described gout as a discharge of the four humors of the body in unbalanced amounts into the joints. - The word Gout was first used in 1200s AD by Dominican monk Randolphus of Bocking and was derived from the Latin word 'Gutta'. - Aulus Cornelius Celsus discovered many symptoms of gout. - ## Pathophysiology Gout occurs when mono-sodium urate crystals form on the articular cartilage of joints, on tendons, and in the surrounding tissues. Purine metabolism gives rise to uric acid, which is normally excreted in the urine. Defects in the kidney may cause uric acid to build up in the blood, leading to hyperuricemia, and the subsequent formation of gout crystals. ## Differentiating Gout from other Diseases Gout needs to be differentiated from other diseases such as cellulitis, rheumatoid arthritis, septic arthritis and sarcoidosis as they present with similar symptoms. ## Epidemiology and Demographics Gout affects men in age group 40-50 years. It is more common in people from the Pacific Islands, and New Zealand. In the United States, gout is twice as prevalent in African American males as it is in Caucasians. ## Risk Factors Several factors may put a person at risk for developing gout. These include the presence of; hypertension, diabetes, hypercholesterolemia, obesity, and alcohol abuse. Certain medications may also put a person at a higher risk for developing gout. ## Prognosis The prognosis of gout is good if it is treated early, and if the person maintains a healthy lifestyle with modification of their individual risk factors. # Diagnosis ## Symptoms The classic picture of an acute gouty attack, is sudden, excruciating, unexpected and burning pain. There will also be swelling, redness, warmth, and stiffness in the joint. In approximately 75% of first episodes, gout usually attacks the big toe. ## Laboratory Findings A definitive diagnosis of gout is made from light microscopy of the fluid aspirated from the joint. The fluid demonstrates intracellular negatively bi-refringent monosodium urate crystals and polymorphonuclear leukocytes in the synovial fluid. Although hyperuricemia is a common feature of gout, a high uric acid level does not necessarily mean a person will develop gout. ## X-ray An x-ray is done when gout is suspected to rule out other abnormalities of the bone that may be causing the pain. Most commonly in gout, the x-ray will show no abnormalities, or a small amount of soft tissue swelling. # Treatment ## Medical Therapy The first goal of therapy when treating gout, is pain relief. This can be acheived with NSAIDs, and oral or intra-articular glucocorticoids. If colchicine is given, it should be taken within the first 12 hours of the attack. Other, less standard methods of treatment include the use of hemorrhoidal ointment, ice, increasing mobility, and acetazolamide. ## Surgery For extreme cases of gout, surgery may be necessary to remove large tophi and correct joint deformity. ## Secondary Prevention There are several methods used to prevent a re-occurrence of gout. Dietary changes include reducing the intake of foods that increase the levels of purine in blood, such as protein and alcohol. Several foods, and vitamin C have been thought to decrease the levels of purine in the blood. Modification of the risk factors for gout has been shown to also be beneficial in reducing the reoccurrence of gout. There are medications which can increase the excretion of uric acid, and reduce uric acid levels through other mechanisms.	https://www.wikidoc.org/index.php/Gout_overview
c9d3d8aa72381ec43780ab7ec75350f698a73b41	wikidoc	Grace Fernald	Grace Fernald Grace Fernald – A Pioneer in Literacy Instruction Noted educational psychologist, Grace Fernald (1879-1950) was an influential figure in early twentieth century literacy education. Fernald established “the first clinic for remedial instruction in 1921 at the University of California, Los Angeles” (Smith, 2002, p. 181). Tracing tactile learning tendencies back to Quintilian, Seguin, and Montessori, Fernald’s kinesthetic spelling and reading method prompted struggling students to trace words. Years of research culminated in 1943 with her classic work, Remedial Techniques in Basic School Subjects. The popular kinesthetic method anchors modern instruction in the areas of special education and remedial reading. Kinesthetic learning is also included as one of Howard Gardner's multiple intelligences. Fernald’s notion of incorporating the physical with the auditory, verbal, and visual elements of reading instruction, now known as , multimodal learning, or multisensory imagery, continues to guide educators today. # Fernald’s Early Years and Education Grace Maxwell Fernald was born on November 29, 1879 in Clyde, Ohio. Following a youth spent in New York and New Jersey, Fernald graduated from high school and then attended college at Mt. Holyoke and Bryn Mawr. In 1907 she received her doctorate in psychology from the University of Chicago. By 1911 Fernald had accepted a position at UCLA. She eventually became head of the Psychology Department and Laboratory at the State Normal School. It was at the UCLA clinic where her research into the reading and writing processes gained fame. # Early Research of the Fernald Method The 1921 Journal of Educational Research contains Fernald’s foundational study of four boys who learn to spell and read by her kinesthetic method. This method influenced other researchers working at the same time in the field of reading difficulties. Notable examples include Samuel Orton and Anna Gillingham. The article in the Journal of Educational Research, “The Effect of Kinaesthetic Factors in the Development of Word Recognition in the Case of Non-Readers” (Fernald & Keller, p. 355), outlines five phases of the kinesthetic method. With an emphasis on student choice, focal words are generated by the students during the first stage. Each word is introduced by the teacher who writes it on the chalkboard. The student repeats the word while tracing it on the board. When the student is confident that he knows the word, he attempts to write it while saying each syllable. Successful word study is followed by phase two where sentences are created in a similar fashion. The third step incorporates a student-selected book where words from specific paragraphs are isolated for reading. In the fourth phase, the student is asked to read whole phrases from the paragraphs. Finally, the student is encouraged to do silent reading on his own for the fifth phase. After some time all four boys successfully learned to read well enough to perform at grade level. Follow-ups with the participants reflected the maintenance of reading levels and for some avid readers, additional leaps in reading proficiency. Though not asserting widespread generalizability, Fernald and Keller enumerate several findings. One conclusion of interest today describes each student learning by analogy, demonstrating the “ability to pronounce new words if they resemble words he has already learned” (p. 375). This is a compensatory strategy currently used. Overall, Fernald and Keller’s acknowledgement that students “learned to read quite easily by ordinary methods when they were given individual instruction and proper motivation” remains evident in such popular programs as Reading Recovery by Marie Clay. # Summary of Fernald’s Career On the eve of Fernald’s retirement from the UCLA clinic, Time magazine (1948, July 12) highlights the story of one boy’s reading adventure in Fernald’s clinic. The title of the article, “Reading by Touch” aptly reflects the Fernald method. Stepping down after 27 years, Fernald sums up the theory behind her “kinesthetic method” with the explanation that “reading difficulties occur most frequently in people who lack the ability to summon up a mental picture of the way a word looks” . Her only requirements for entrance into the clinic program were for students to have average intelligence and for parents to continue with the clinic as long as necessary. According to Time, remediation required from “two months to two years” for the students to reach their grade level reading equivalent. Though the article includes some criticism of the Fernald method, in the end it is a positive portrayal of a committed educator. # A Child’s View of Fernald’s Method A more powerful account of the influence of the kinesthetic method practiced in Fernald’s clinic is presented by the International Reading Association’s Special Interest Group in the history of reading. In the spring 1998 edition of the History of Reading News a former student of Fernald’s kinesthetic method recalls his experiences in the clinic setting. He describes a typical session with one of the student teachers where there was even finger painting. The student, now an esteemed doctor, researcher, and chair of psychiatry at a major New York hospital, wonders about the “life changes for some of the other boys as a result of her help and ministrations.” He admits that he “still uses aspects of the Fernald method to this day.” It is a moving testimonial. # A Parent’s View of Fernald’s Method An additional article written by the mother of the same former student was also included in the 1998 edition of the History of Reading News. Though not as detailed, the passage reminds educators that their work impacts not only the student, but the entire family. The parents contacted Grace Fernald in an effort to support their intelligent second-grade son who was struggling in school. The mother even recounts a visit to Fernald’s home. Grace Fernald, the caring teacher, comes alive through these two touching accounts of one boy’s success story. # Fernald’s Influence on Education Upon Fernald’s passing in 1950, her peers praised the tremendous impact of her UCLA clinic endeavors. “Grace Fernald developed and directed the clinical school. The children and adults helped by study and treatment in this clinic and the teachers and psychologists observing and learning in the clinic school run into the thousands.”	Grace Fernald Grace Fernald – A Pioneer in Literacy Instruction Noted educational psychologist, Grace Fernald (1879-1950) was an influential figure in early twentieth century literacy education. Fernald established “the first clinic for remedial instruction in 1921 at the University of California, Los Angeles” (Smith, 2002, p. 181). Tracing tactile learning tendencies back to Quintilian, Seguin, and Montessori, Fernald’s kinesthetic spelling and reading method prompted struggling students to trace words. Years of research culminated in 1943 with her classic work, Remedial Techniques in Basic School Subjects. The popular kinesthetic method anchors modern instruction in the areas of special education and remedial reading. Kinesthetic learning is also included as one of Howard Gardner's multiple intelligences. Fernald’s notion of incorporating the physical with the auditory, verbal, and visual elements of reading instruction, now known as [VAKT][1], multimodal learning, or multisensory imagery, continues to guide educators today. # Fernald’s Early Years and Education Grace Maxwell Fernald was born on November 29, 1879 in Clyde, Ohio. Following a youth spent in New York and New Jersey, Fernald graduated from high school and then attended college at Mt. Holyoke and Bryn Mawr. In 1907 she received her doctorate in psychology from the University of Chicago. By 1911 Fernald had accepted a position at UCLA. She eventually became head of the Psychology Department and Laboratory at the State Normal School. It was at the UCLA clinic where her research into the reading and writing processes gained fame.[2] # Early Research of the Fernald Method The 1921 Journal of Educational Research contains Fernald’s foundational study of four boys who learn to spell and read by her kinesthetic method. This method influenced other researchers working at the same time in the field of reading difficulties. Notable examples include Samuel Orton and Anna Gillingham. The article in the Journal of Educational Research, “The Effect of Kinaesthetic Factors in the Development of Word Recognition in the Case of Non-Readers” (Fernald & Keller, p. 355), outlines five phases of the kinesthetic method. With an emphasis on student choice, focal words are generated by the students during the first stage. Each word is introduced by the teacher who writes it on the chalkboard. The student repeats the word while tracing it on the board. When the student is confident that he knows the word, he attempts to write it while saying each syllable. Successful word study is followed by phase two where sentences are created in a similar fashion. The third step incorporates a student-selected book where words from specific paragraphs are isolated for reading. In the fourth phase, the student is asked to read whole phrases from the paragraphs. Finally, the student is encouraged to do silent reading on his own for the fifth phase. After some time all four boys successfully learned to read well enough to perform at grade level. Follow-ups with the participants reflected the maintenance of reading levels and for some avid readers, additional leaps in reading proficiency. Though not asserting widespread generalizability, Fernald and Keller enumerate several findings. One conclusion of interest today describes each student learning by analogy, demonstrating the “ability to pronounce new words if they resemble words he has already learned” (p. 375). This is a compensatory strategy currently used. Overall, Fernald and Keller’s acknowledgement that students “learned to read quite easily by ordinary methods when they were given individual instruction and proper motivation” remains evident in such popular programs as Reading Recovery by Marie Clay. # Summary of Fernald’s Career On the eve of Fernald’s retirement from the UCLA clinic, Time magazine (1948, July 12) highlights the story of one boy’s reading adventure in Fernald’s clinic. The title of the article, “Reading by Touch” aptly reflects the Fernald method. Stepping down after 27 years, Fernald sums up the theory behind her “kinesthetic method” with the explanation that “reading difficulties occur most frequently in people who lack the ability to summon up a mental picture of the way a word looks” [3]. Her only requirements for entrance into the clinic program were for students to have average intelligence and for parents to continue with the clinic as long as necessary. According to Time, remediation required from “two months to two years” for the students to reach their grade level reading equivalent. Though the article includes some criticism of the Fernald method, in the end it is a positive portrayal of a committed educator. # A Child’s View of Fernald’s Method A more powerful account of the influence of the kinesthetic method practiced in Fernald’s clinic is presented by the International Reading Association’s Special Interest Group in the history of reading. In the spring 1998 edition of the History of Reading News a former student of Fernald’s kinesthetic method recalls his experiences in the clinic setting. He describes a typical session with one of the student teachers where there was even finger painting. The student, now an esteemed doctor, researcher, and chair of psychiatry at a major New York hospital, wonders about the “life changes for some of the other boys as a result of her help and ministrations.” He admits that he “still uses aspects of the Fernald method to this day.” It is a moving testimonial.[4] # A Parent’s View of Fernald’s Method An additional article written by the mother of the same former student was also included in the 1998 edition of the History of Reading News. Though not as detailed, the passage reminds educators that their work impacts not only the student, but the entire family. The parents contacted Grace Fernald in an effort to support their intelligent second-grade son who was struggling in school. The mother even recounts a visit to Fernald’s home. Grace Fernald, the caring teacher, comes alive through these two touching accounts of one boy’s success story. [5] # Fernald’s Influence on Education Upon Fernald’s passing in 1950, her peers praised the tremendous impact of her UCLA clinic endeavors. “Grace Fernald developed and directed the clinical school. The children and adults helped by study and treatment in this clinic and the teachers and psychologists observing and learning in the clinic school run into the thousands.” [6]	https://www.wikidoc.org/index.php/Grace_Fernald
e3edb559b2abd5ed96fb89097acc34b71e134d9a	wikidoc	Gram staining	Gram staining Gram staining (or Gram's method) is an empirical method of differentiating bacterial species into two large groups (Gram-positive and Gram-negative) based on the chemical and physical properties of their cell walls. The method is named after its inventor, the Danish scientist Hans Christian Gram (1853–1938), who developed the technique in 1884 to discriminate between pneumococci and Klebsiella pneumoniae bacteria. # Uses ## Research Gram staining is one of the most useful staining procedures in the traditional bacteriological laboratory. The technique is used as a tool for the differentiation of Gram-positive and Gram-negative bacteria, as a first step to determine the identity of a particular bacterial sample. The Gram stain is not an infallible tool for diagnosis, identification, or phylogeny, however. It is of extremely limited use in environmental microbiology, and has been largely superseded by molecular techniques even in the medical microbiology lab. Given that some organisms are gram-variable (i.e. they may stain either negative or positive), and that some organisms are not susceptible to either stain used by the Gram technique, its true utility to researchers should be considered limited and specific. In a modern environmental or molecular microbiology lab, most identification is done using genetic sequences and other molecular techniques, which are far more specific and information-rich than differential staining. ## Medical Gram stains are performed on body fluid or biopsy when infection is suspected. It yields results much more quickly than culture, and is especially important when infection would make an important difference in the patient's treatment and prognosis; examples are cerebrospinal fluid for meningitis and synovial fluid for septic arthritis. As a general rule of thumb (which has exceptions), Gram-negative bacteria are more pathogenic due to their outer membrane structure. The presence of a capsule will often increase the virulence of a pathogen. Additionally, Gram-negative bacteria have lipopolysaccharide in their outer membrane, an endotoxin which increases the severity of inflammation. This inflammation may be so severe that septic shock may occur. Gram-positive infections are generally less severe because the human body does not contain peptidoglycan; in fact, humans produce an enzyme (lysozyme) that attacks the open peptidoglycan layer of Gram-positive bacteria. Gram-positive bacteria are also frequently much more susceptible to beta-lactam antibiotics, such as penicillin. Exceptions to the rule include branching and filamentous Gram-positive bacteria such as Mycobacterium tuberculosis and other agents of tuberculosis, or Nocardia species, the agents of nocardiosis and some types of actinomycetoma. These organisms present unique problems in diagnosis and treatment, and special stains such as the Ziehl-Neelsen stain and the Kinyoun stain are used in their laboratory workup. # Staining mechanism Gram-positive bacteria have a thick mesh-like cell wall made of peptidoglycan (90% of cell wall), which stain purple and Gram-negative bacteria have a thinner layer (10% of cell wall), which stain pink. Gram-negative bacteria also have an additional outer membrane which contains lipids, and is separated from the cell wall by the periplasmic space. There are four basic steps of the Gram stain, which include applying a primary stain (crystal violet) to a heat-fixed smear of a bacterial culture, followed by the addition of a mordant (Gram's iodine), rapid decolorization with alcohol or acetone, and counterstaining with safranin or basic fuchsin. Crystal violet (CV) dissociates in aqueous solutions into CV+ and chloride (Cl–) ions. These ions penetrate through the cell wall and cell membrane of both Gram-positive and Gram-negative cells. The CV+ ion interacts with negatively charged components of bacterial cells and stains the cells purple. Iodine (I– or I3–) interacts with CV+ and forms large complexes of crystal violet and iodine (CV–I) within the inner and outer layers of the cell. When a decolorizer such as alcohol or acetone is added, it interacts with the lipids of the cell membrane. A Gram-negative cell will lose its outer membrane and the peptidoglycan layer is left exposed. The CV–I complexes are washed from the Gram-negative cell along with the outer membrane. In contrast, a Gram-positive cell becomes dehydrated from an ethanol treatment. The large CV–I complexes become trapped within the Gram-positive cell due to the multilayered nature of its peptidoglycan. The decolorization step is critical and must be timed correctly; the crystal violet stain will be removed from both Gram-positive and negative cells if the decolorizing agent is left on too long (a matter of seconds). After decolorization, the Gram-positive cell remains purple and the Gram-negative cell loses its purple color. Counterstain, which is usually positively-charged safranin or basic fuchsin, is applied last to give decolorized Gram-negative bacteria a pink or red color. Some bacteria, after staining with the Gram stain, yield a Gram-variable pattern: a mix of pink and purple cells are seen. The genera Actinomyces, Arthobacter, Corynebacterium, Mycobacterium, and Propionibacterium have cell walls particularly sensitive to breakage during cell division, resulting in Gram-negative staining of these Gram-positive cells. In cultures of Bacillus, Butyrivibrio, and Clostridium a decrease in peptidoglycan thickness during growth coincides with an increase in the number of cells that stain Gram-negative In addition, in all bacteria stained using the Gram stain, the age of the culture may influence the results of the stain. # Gram staining protocol - Make a slide of tissue or body fluid that is to be stained. Heat the slide for few seconds until it becomes hot to the touch so that bacteria are firmly mounted to the slide. - Add the primary stain crystal violet and incubate 1 minute. This step colors all cells violet. - Add Gram's iodine, for 30 seconds. It is not a stain; it is a mordant. It doesn't give color directly to the bacteria but it fixes the crystal violet to the bacterial cell wall. All cells remain violet. - Wash with ethanol and acetone, the Decolorizer. If the bacteria is Gram-positive it will retain the primary stain. If it is Gram-negative it will lose the primary stain and appear colorless. - Add the secondary stain, safranin, and incubate 1 min, then wash with water for a maximum of 5 seconds. If the bacteria is Gram-positive then the cell will retain the primary stain, will not take the secondary stain, and will appear black-violet. If the bacteria is Gram-negative then the cell will lose the primary stain, take secondary stain, and will appear red-pink. Gram Stain is 2 g of 90% crystal violet dissolved in 20 ml of 95% ethyl alcohol. Gram's iodine is 1 g of iodine, 2 g of potassium iodide, dissolved in 300 ml of distilled water. Decolorizer is 50% ethyl alcohol, 50% acetone. In addition it is now common to use basic fuchsin instead of safranin.	Gram staining Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Gram staining (or Gram's method) is an empirical method of differentiating bacterial species into two large groups (Gram-positive and Gram-negative) based on the chemical and physical properties of their cell walls.[1] The method is named after its inventor, the Danish scientist Hans Christian Gram (1853–1938), who developed the technique in 1884 to discriminate between pneumococci and Klebsiella pneumoniae bacteria.[2] # Uses ## Research Gram staining is one of the most useful staining procedures in the traditional bacteriological laboratory.[3] The technique is used as a tool for the differentiation of Gram-positive and Gram-negative bacteria, as a first step to determine the identity of a particular bacterial sample.[4] The Gram stain is not an infallible tool for diagnosis, identification, or phylogeny, however. It is of extremely limited use in environmental microbiology, and has been largely superseded by molecular techniques even in the medical microbiology lab. Given that some organisms are gram-variable (i.e. they may stain either negative or positive), and that some organisms are not susceptible to either stain used by the Gram technique, its true utility to researchers should be considered limited and specific. In a modern environmental or molecular microbiology lab, most identification is done using genetic sequences and other molecular techniques, which are far more specific and information-rich than differential staining. ## Medical Gram stains are performed on body fluid or biopsy when infection is suspected. It yields results much more quickly than culture, and is especially important when infection would make an important difference in the patient's treatment and prognosis; examples are cerebrospinal fluid for meningitis and synovial fluid for septic arthritis.[3][5] As a general rule of thumb (which has exceptions), Gram-negative bacteria are more pathogenic due to their outer membrane structure. The presence of a capsule will often increase the virulence of a pathogen. Additionally, Gram-negative bacteria have lipopolysaccharide in their outer membrane, an endotoxin which increases the severity of inflammation. This inflammation may be so severe that septic shock may occur. Gram-positive infections are generally less severe because the human body does not contain peptidoglycan; in fact, humans produce an enzyme (lysozyme) that attacks the open peptidoglycan layer of Gram-positive bacteria. Gram-positive bacteria are also frequently much more susceptible to beta-lactam antibiotics, such as penicillin. Exceptions to the rule include branching and filamentous Gram-positive bacteria such as Mycobacterium tuberculosis and other agents of tuberculosis, or Nocardia species, the agents of nocardiosis and some types of actinomycetoma. These organisms present unique problems in diagnosis and treatment, and special stains such as the Ziehl-Neelsen stain and the Kinyoun stain are used in their laboratory workup. # Staining mechanism Gram-positive bacteria have a thick mesh-like cell wall made of peptidoglycan (90% of cell wall), which stain purple and Gram-negative bacteria have a thinner layer (10% of cell wall), which stain pink. Gram-negative bacteria also have an additional outer membrane which contains lipids, and is separated from the cell wall by the periplasmic space. There are four basic steps of the Gram stain, which include applying a primary stain (crystal violet) to a heat-fixed smear of a bacterial culture, followed by the addition of a mordant (Gram's iodine), rapid decolorization with alcohol or acetone, and counterstaining with safranin or basic fuchsin. Crystal violet (CV) dissociates in aqueous solutions into CV+ and chloride (Cl–) ions. These ions penetrate through the cell wall and cell membrane of both Gram-positive and Gram-negative cells. The CV+ ion interacts with negatively charged components of bacterial cells and stains the cells purple. Iodine (I– or I3–) interacts with CV+ and forms large complexes of crystal violet and iodine (CV–I) within the inner and outer layers of the cell. When a decolorizer such as alcohol or acetone is added, it interacts with the lipids of the cell membrane. A Gram-negative cell will lose its outer membrane and the peptidoglycan layer is left exposed. The CV–I complexes are washed from the Gram-negative cell along with the outer membrane. In contrast, a Gram-positive cell becomes dehydrated from an ethanol treatment. The large CV–I complexes become trapped within the Gram-positive cell due to the multilayered nature of its peptidoglycan. The decolorization step is critical and must be timed correctly; the crystal violet stain will be removed from both Gram-positive and negative cells if the decolorizing agent is left on too long (a matter of seconds). After decolorization, the Gram-positive cell remains purple and the Gram-negative cell loses its purple color. Counterstain, which is usually positively-charged safranin or basic fuchsin, is applied last to give decolorized Gram-negative bacteria a pink or red color.[6][7] Some bacteria, after staining with the Gram stain, yield a Gram-variable pattern: a mix of pink and purple cells are seen. The genera Actinomyces, Arthobacter, Corynebacterium, Mycobacterium, and Propionibacterium have cell walls particularly sensitive to breakage during cell division, resulting in Gram-negative staining of these Gram-positive cells. In cultures of Bacillus, Butyrivibrio, and Clostridium a decrease in peptidoglycan thickness during growth coincides with an increase in the number of cells that stain Gram-negative[8] In addition, in all bacteria stained using the Gram stain, the age of the culture may influence the results of the stain. # Gram staining protocol - Make a slide of tissue or body fluid that is to be stained. Heat the slide for few seconds until it becomes hot to the touch so that bacteria are firmly mounted to the slide. - Add the primary stain crystal violet and incubate 1 minute. This step colors all cells violet. - Add Gram's iodine, for 30 seconds. It is not a stain; it is a mordant. It doesn't give color directly to the bacteria but it fixes the crystal violet to the bacterial cell wall. All cells remain violet. - Wash with ethanol and acetone, the Decolorizer. If the bacteria is Gram-positive it will retain the primary stain. If it is Gram-negative it will lose the primary stain and appear colorless. - Add the secondary stain, safranin, and incubate 1 min, then wash with water for a maximum of 5 seconds. If the bacteria is Gram-positive then the cell will retain the primary stain, will not take the secondary stain, and will appear black-violet. If the bacteria is Gram-negative then the cell will lose the primary stain, take secondary stain, and will appear red-pink. Gram Stain is 2 g of 90% crystal violet dissolved in 20 ml of 95% ethyl alcohol. Gram's iodine is 1 g of iodine, 2 g of potassium iodide, dissolved in 300 ml of distilled water. Decolorizer is 50% ethyl alcohol, 50% acetone.[2] In addition it is now common to use basic fuchsin instead of safranin.	https://www.wikidoc.org/index.php/Gram%27s_stain
1e387ab689085a0f85c9dfd2be377fe3b0e68786	wikidoc	Gram-negative	Gram-negative # Overview Gram-negative bacteria are those that do not retain crystal violet dye in the Gram staining protocol. Gram-positive bacteria will retain the dark blue dye after an alcohol wash. In a Gram stain test, a counterstain (commonly Safranin) is added after the crystal violet, colouring all Gram-negative bacteria a red or pink colour. The test itself is useful in classifying two distinctly different types of bacteria based on structural differences in their cell walls. Many species of Gram-negative bacteria are pathogenic, meaning they can cause disease in a host organism. This pathogenic capability is usually associated with certain components of Gram-negative cell walls, in particular the lipopolysaccharide (also known as LPS or endotoxin) layer. The LPS is the trigger which the body's innate immune response receptors sense to begin a cytokine reaction. It is toxic to the host. It is this response which begins the inflammation cycle in tissues and blood vessels. # Characteristics The following characteristics are displayed by Gram-negative bacteria: - Cell walls only contain a few layers of peptidoglycan (which is present in much higher levels in Gram-positive bacteria) - Cells are surrounded by an outer membrane containing lipopolysaccharide (which consists of Lipid A, core polysaccharide, and O-polysaccharide) outside the peptidoglycan layer - Porins exist in the outer membrane, which act like pores for particular molecules - There is a space between the layers of peptidoglycan and the secondary cell membrane called the periplasmic space - The S-layer is directly attached to the outer membrane, rather than the peptidoglycan - If present, flagella have four supporting rings instead of two - No teichoic acids or lipoteichoic acids are present - Lipoproteins are attached to the polysaccharide backbone whereas in Gram-positive bacteria no lipoproteins are present - Most do not sporulate (Coxiella burnetti forms spore-like structures). # Example species The proteobacteria are a major group of Gram-negative bacteria, including Escherichia coli, Salmonella, and other Enterobacteriaceae, Pseudomonas, Moraxella, Helicobacter, Stenotrophomonas, Bdellovibrio, acetic acid bacteria, Legionella and alpha-proteobacteria as Wolbachia and many others. Other notable groups of Gram-negative bacteria include the cyanobacteria, spirochaetes, green sulfur and green non-sulfur bacteria. Crenarchaeota: Unique because most bacteria have gram-positive molecules in their capsules, it has gram-negative. Medically relevant Gram-negative cocci include three organisms, which cause a sexually transmitted disease (Neisseria gonorrhoeae), a meningitis (Neisseria meningitidis), and respiratory symptoms (Moraxella catarrhalis). Medically relevant Gram-negative bacilli include a multitude of species. Some of them primarily cause respiratory problems (Hemophilus influenzae, Klebsiella pneumoniae, Legionella pneumophila, Pseudomonas aeruginosa), primarily urinary problems (Escherichia coli, Proteus mirabilis, Enterobacter cloacae, Serratia marcescens), and primarily gastrointestinal problems (Helicobacter pylori, Salmonella enteritidis, Salmonella typhi). Nosocomial gram negative bacteria include Acinetobacter baumanii, which cause bacteremia, secondary meningitis, and ventilator-associated pneumonia in intensive care units of hospital establishments. # Medical treatment One of the several unique characteristics of Gram-negative bacteria is the outer membrane. This outer membrane is responsible for protecting the bacteria from several antibiotics, dyes, and detergents which would normally damage the inner membrane or cell wall (peptidoglycan). The outer membrane provides these bacteria with resistance to lysozyme and penicillin. Fortunately, alternative medicinal treatments such as lysozyme with EDTA, and the antibiotic ampicillin have been developed to combat the protective outer membrane of some pathogenic Gram-negative organisms. Other drugs can be used, namely chloramphenicol, streptomycin, and nalidixic acid.	Gram-negative Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview Gram-negative bacteria are those that do not retain crystal violet dye in the Gram staining protocol.[1] Gram-positive bacteria will retain the dark blue dye after an alcohol wash. In a Gram stain test, a counterstain (commonly Safranin) is added after the crystal violet, colouring all Gram-negative bacteria a red or pink colour. The test itself is useful in classifying two distinctly different types of bacteria based on structural differences in their cell walls.[2] Many species of Gram-negative bacteria are pathogenic, meaning they can cause disease in a host organism. This pathogenic capability is usually associated with certain components of Gram-negative cell walls, in particular the lipopolysaccharide (also known as LPS or endotoxin) layer.[1] The LPS is the trigger which the body's innate immune response receptors sense to begin a cytokine reaction. It is toxic to the host. It is this response which begins the inflammation cycle in tissues and blood vessels. # Characteristics The following characteristics are displayed by Gram-negative bacteria: - Cell walls only contain a few layers of peptidoglycan (which is present in much higher levels in Gram-positive bacteria) - Cells are surrounded by an outer membrane containing lipopolysaccharide (which consists of Lipid A, core polysaccharide, and O-polysaccharide) outside the peptidoglycan layer - Porins exist in the outer membrane, which act like pores for particular molecules - There is a space between the layers of peptidoglycan and the secondary cell membrane called the periplasmic space - The S-layer is directly attached to the outer membrane, rather than the peptidoglycan - If present, flagella have four supporting rings instead of two - No teichoic acids or lipoteichoic acids are present - Lipoproteins are attached to the polysaccharide backbone whereas in Gram-positive bacteria no lipoproteins are present - Most do not sporulate (Coxiella burnetti forms spore-like structures). # Example species The proteobacteria are a major group of Gram-negative bacteria, including Escherichia coli, Salmonella, and other Enterobacteriaceae, Pseudomonas, Moraxella, Helicobacter, Stenotrophomonas, Bdellovibrio, acetic acid bacteria, Legionella and alpha-proteobacteria as Wolbachia and many others. Other notable groups of Gram-negative bacteria include the cyanobacteria, spirochaetes, green sulfur and green non-sulfur bacteria. Crenarchaeota: Unique because most bacteria have gram-positive molecules in their capsules, it has gram-negative. Medically relevant Gram-negative cocci include three organisms, which cause a sexually transmitted disease (Neisseria gonorrhoeae), a meningitis (Neisseria meningitidis), and respiratory symptoms (Moraxella catarrhalis). Medically relevant Gram-negative bacilli include a multitude of species. Some of them primarily cause respiratory problems (Hemophilus influenzae, Klebsiella pneumoniae, Legionella pneumophila, Pseudomonas aeruginosa), primarily urinary problems (Escherichia coli, Proteus mirabilis, Enterobacter cloacae, Serratia marcescens), and primarily gastrointestinal problems (Helicobacter pylori, Salmonella enteritidis, Salmonella typhi). Nosocomial gram negative bacteria include Acinetobacter baumanii, which cause bacteremia, secondary meningitis, and ventilator-associated pneumonia in intensive care units of hospital establishments. # Medical treatment One of the several unique characteristics of Gram-negative bacteria is the outer membrane. This outer membrane is responsible for protecting the bacteria from several antibiotics, dyes, and detergents which would normally damage the inner membrane or cell wall (peptidoglycan). The outer membrane provides these bacteria with resistance to lysozyme and penicillin. Fortunately, alternative medicinal treatments such as lysozyme with EDTA, and the antibiotic ampicillin have been developed to combat the protective outer membrane of some pathogenic Gram-negative organisms. Other drugs can be used, namely chloramphenicol, streptomycin, and nalidixic acid.	https://www.wikidoc.org/index.php/Gram-negative
0be1205025fa844c9ddb2185a9946135984c01ab	wikidoc	Gram-positive	Gram-positive # Overview Gram-positive bacteria are those that retain a crystal violet dye during the Gram stain process. Gram-positive bacteria appear blue or violet under a microscope, while Gram-negative bacteria appear red or pink. The Gram classification system is empirical, and largely based on differences in cell wall structure. The purpose of Gram staining is to visually differentiate groups of bacteria, primarily for identification. # Characteristics The following characteristics are generally present in a Gram-positive bacterium: - A very thick cell wall (peptidoglycan). - If a flagellum is present, it contains two rings for support as opposed to four in Gram-negative bacteria because Gram-positive bacteria have only one membrane layer. - Teichoic acids and lipoteichoic acids are present, which serve to act as chelating agents, and also for certain types of adherence. # History of Gram positive In the original bacterial phyla, the Gram-positive forms made up the phylum Firmicutes, a name now used for the largest group. It includes many well-known genera such as Bacillus, Listeria, Staphylococcus, Streptococcus, Enterococcus, and Clostridium. It has also been expanded to include the Mollicutes, bacteria like Mycoplasma that lack cell walls and so cannot be stained by Gram, but are derived from such forms. The actinobacteria are another major group of Gram-positive bacteria; they and the Firmicutes are referred to as the high and low G+C groups based on the guanosine and cytosine content of their DNA. If the second membrane is a derived condition, the two may have been basal among the bacteria; otherwise they are probably a relatively recent monophyletic group. They have been considered as possible ancestors for the archaeans and eukaryotes, both because they are unusual in lacking the second membrane and because of various biochemical similarities such as the presence of sterols. The Deinococcus-Thermus bacteria also have Gram-positive stains, although they are structurally similar to Gram-negative bacteria. Both Gram-positive and Gram-negative bacteria may have a membrane called an S-layer. In Gram-negative bacteria, the S-layer is directly attached to the outer membrane. In Gram-positive bacteria, the S-layer is attached to the peptidoglycan layer. Unique to Gram-positive bacteria is the presence of teichoic acids in the cell wall. Some particular teichoic acids, lipoteichoic acids, have a lipid component and can assist in anchoring peptidoglycan, as the lipid component is embedded in the membrane.	Gram-positive Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview Gram-positive bacteria are those that retain a crystal violet dye during the Gram stain process.[1] Gram-positive bacteria appear blue or violet under a microscope, while Gram-negative bacteria appear red or pink. The Gram classification system is empirical, and largely based on differences in cell wall structure.[2] The purpose of Gram staining is to visually differentiate groups of bacteria, primarily for identification. # Characteristics The following characteristics are generally present in a Gram-positive bacterium:[3] - A very thick cell wall (peptidoglycan). - If a flagellum is present, it contains two rings for support as opposed to four in Gram-negative bacteria because Gram-positive bacteria have only one membrane layer. - Teichoic acids and lipoteichoic acids are present, which serve to act as chelating agents, and also for certain types of adherence. # History of Gram positive In the original bacterial phyla, the Gram-positive forms made up the phylum Firmicutes, a name now used for the largest group. It includes many well-known genera such as Bacillus, Listeria, Staphylococcus, Streptococcus, Enterococcus, and Clostridium. It has also been expanded to include the Mollicutes, bacteria like Mycoplasma that lack cell walls and so cannot be stained by Gram, but are derived from such forms. The actinobacteria are another major group of Gram-positive bacteria; they and the Firmicutes are referred to as the high and low G+C groups based on the guanosine and cytosine content of their DNA. If the second membrane is a derived condition, the two may have been basal among the bacteria; otherwise they are probably a relatively recent monophyletic group. They have been considered as possible ancestors for the archaeans and eukaryotes, both because they are unusual in lacking the second membrane and because of various biochemical similarities such as the presence of sterols. The Deinococcus-Thermus bacteria also have Gram-positive stains, although they are structurally similar to Gram-negative bacteria. Both Gram-positive and Gram-negative bacteria may have a membrane called an S-layer. In Gram-negative bacteria, the S-layer is directly attached to the outer membrane. In Gram-positive bacteria, the S-layer is attached to the peptidoglycan layer. Unique to Gram-positive bacteria is the presence of teichoic acids in the cell wall. Some particular teichoic acids, lipoteichoic acids, have a lipid component and can assist in anchoring peptidoglycan, as the lipid component is embedded in the membrane.	https://www.wikidoc.org/index.php/Gram-positive
4a81af2ce61ef04c4d690a7a877bedbe22c02358	wikidoc	Greater cornu	Greater cornu The greater cornua project backward from the lateral borders of the body; they are flattened from above downward and diminish in size from before backward; each ends in a tubercle to which is fixed the lateral hyothyroid ligament. The upper surface is rough close to its lateral border, for muscular attachments: the largest of these are the origins of the hyoglossus and Constrictor pharyngis medius which extend along the whole length of the cornu; the digastric muscle and stylohyoid muscle have small insertions in front of these near the junction of the body with the cornu. To the medial border the hyothyroid membrane is attached, while the anterior half of the lateral border gives insertion to the thyrohyoid.	Greater cornu Template:Infobox Bone The greater cornua project backward from the lateral borders of the body; they are flattened from above downward and diminish in size from before backward; each ends in a tubercle to which is fixed the lateral hyothyroid ligament. The upper surface is rough close to its lateral border, for muscular attachments: the largest of these are the origins of the hyoglossus and Constrictor pharyngis medius which extend along the whole length of the cornu; the digastric muscle and stylohyoid muscle have small insertions in front of these near the junction of the body with the cornu. To the medial border the hyothyroid membrane is attached, while the anterior half of the lateral border gives insertion to the thyrohyoid.	https://www.wikidoc.org/index.php/Greater_cornu
8fc232dc0702e92085c518d2db9aa4a283d6d6be	wikidoc	Gregarinasina	Gregarinasina The gregarines are a group of Apicomplexan protozoa, classified as the Gregarinasina or Gregarinea. The gregarines are able to move and change direction along a surface through gliding motility without the use of cilia, flagella, or lamellipodia . This is accomplished through the use of an actin and myosin complex . The complexes require an actin cytoskeleton to perform their gliding motions . In the proposed ‘capping’ model, an uncharacterized protein complex moves rearward, moving the parasites forward . The large (roughly half a millimeter) parasites inhabit the intestines of a large number of invertebrates. They are not found in humans. However, Gregarinasina is closely related to both Toxoplasma and Plasmodium, which cause toxoplasmosis and malaria, respectively. Both protists use protein complexes similar to those that are formed by the gregarines for gliding motility and to invade target cells . This makes them an excellent model for studying gliding motility with the goal of creating toxoplasmosis and malaria treatment options. # Bibliography - Heintzelman, M B. 2004. Actin and Myosin in Gregarina polymorpha. Cell Motil Cytoskeleton 58:83-95. - Menard, R. 2001. Gliding Motility and Cell Invasion by Apicomplexa: Insights from the Plasmodium sporozoite. Cell. Microbiol 3: 63-73. - Meissner, M, Schluter, D and Soldati, D. 2002. Role of Toxoplasma Gondii Myosin a in Powering Parasite Gliding and Host Cell Invasion. Science 298: 837-841. - Mitchison, T.J., and Cramer, L.P. 1996. Actin-based cell motility and cell locomotion. Cell 84: 371–379 - Sibley, L.D., Hakansson, S, Carruthers, V. B. 1998. Gliding motility: An efficient mechanism for cell penetration Curr. Biol. 8, 12. - Walker, M M., C Mackenzie, S P Bainbridge, and C Orme. 1979. A Study of the Structure and Gliding Movement of Gregarina garnhami. J Protozool 26: 566-574.	Gregarinasina Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] The gregarines are a group of Apicomplexan protozoa, classified as the Gregarinasina or Gregarinea. The gregarines are able to move and change direction along a surface through gliding motility without the use of cilia, flagella, or lamellipodia [Walker et al., 1979]. This is accomplished through the use of an actin and myosin complex [Heintzelman, 2004]. The complexes require an actin cytoskeleton to perform their gliding motions [Mitchison and Cramer, 1996]. In the proposed ‘capping’ model, an uncharacterized protein complex moves rearward, moving the parasites forward [Sibley et al., 1998]. The large (roughly half a millimeter) parasites inhabit the intestines of a large number of invertebrates. They are not found in humans. However, Gregarinasina is closely related to both Toxoplasma and Plasmodium, which cause toxoplasmosis and malaria, respectively. Both protists use protein complexes similar to those that are formed by the gregarines for gliding motility and to invade target cells [Sibley et al., 1998; Menard, 2001; Meissner et al, 2002]. This makes them an excellent model for studying gliding motility with the goal of creating toxoplasmosis and malaria treatment options. # Bibliography - Heintzelman, M B. 2004. Actin and Myosin in Gregarina polymorpha. Cell Motil Cytoskeleton 58:83-95. - Menard, R. 2001. Gliding Motility and Cell Invasion by Apicomplexa: Insights from the Plasmodium sporozoite. Cell. Microbiol 3: 63-73. - Meissner, M, Schluter, D and Soldati, D. 2002. Role of Toxoplasma Gondii Myosin a in Powering Parasite Gliding and Host Cell Invasion. Science 298: 837-841. - Mitchison, T.J., and Cramer, L.P. 1996. Actin-based cell motility and cell locomotion. Cell 84: 371–379 - Sibley, L.D., Hakansson, S, Carruthers, V. B. 1998. Gliding motility: An efficient mechanism for cell penetration Curr. Biol. 8, 12. - Walker, M M., C Mackenzie, S P Bainbridge, and C Orme. 1979. A Study of the Structure and Gliding Movement of Gregarina garnhami. J Protozool 26: 566-574. Template:WikiDoc Sources	https://www.wikidoc.org/index.php/Gregarinasina
d71d7ff2ac811911f17b96feeae9718fd93d58da	wikidoc	Gross anatomy	Gross anatomy Gross anatomy is the study of anatomy at the macroscopic level. The term gross distinguishes it from other areas of anatomical study, including microscopic anatomy, which must be studied with the aid of a microscope. # Techniques of study Gross anatomy is studied using both invasive and noninvasive methods with the goal of obtaining information about the macroscopic structure and organization of organs and organ systems. Among the most common methods of study is dissection, in which the body of an animal is surgically opened and its organs studied. Endoscopy, in which a video camera-equipped instrument is inserted through a small incision in the subject, may be used to explore the internal organs and other structures of living animals. The anatomy of the circulatory system in a living animal may be studied noninvasively via angiography, a technique in which blood vessels are visualized after being injected with an opaque dye. Other techniques of study include X-ray and MRI. Anatomy is the study of the structure of the body, in medical schools the dissection of the human body (cadaver) is common place. Thought of the only way to learn and teach anatomy by many, many atlas and Dvd's are available as an aid but not a replacement for dissection. # In education Most medical schools require that students complete a course in gross human anatomy. Such courses aim to educate students in basic human anatomy and seek to establish anatomical landmarks that may later be used to aid medical diagnosis. Many schools provide students with cadavers for investigation by dissection, aided by dissectors such as Grant's Dissector, as well as cadaveric atlases (e.g. Rohen's). sk:Topografická anatómia	Gross anatomy Gross anatomy is the study of anatomy at the macroscopic level. The term gross distinguishes it from other areas of anatomical study, including microscopic anatomy, which must be studied with the aid of a microscope. # Techniques of study Gross anatomy is studied using both invasive and noninvasive methods with the goal of obtaining information about the macroscopic structure and organization of organs and organ systems. Among the most common methods of study is dissection, in which the body of an animal is surgically opened and its organs studied. Endoscopy, in which a video camera-equipped instrument is inserted through a small incision in the subject, may be used to explore the internal organs and other structures of living animals. The anatomy of the circulatory system in a living animal may be studied noninvasively via angiography, a technique in which blood vessels are visualized after being injected with an opaque dye. Other techniques of study include X-ray and MRI. Anatomy is the study of the structure of the body, in medical schools the dissection of the human body (cadaver) is common place. Thought of the only way to learn and teach anatomy by many, many atlas and Dvd's are available as an aid but not a replacement for dissection. # In education Most medical schools require that students complete a course in gross human anatomy. Such courses aim to educate students in basic human anatomy and seek to establish anatomical landmarks that may later be used to aid medical diagnosis. Many schools provide students with cadavers for investigation by dissection, aided by dissectors such as Grant's Dissector, as well as cadaveric atlases (e.g. Rohen's). Template:WH Template:WikiDoc Sources sk:Topografická anatómia Template:Jb1	https://www.wikidoc.org/index.php/Gross_anatomy
f3d8ed5ca43f33799cd9c80040bd23149aa30ad7	wikidoc	Ground tissue	Ground tissue The types of ground tissue found in plants develops from ground tissue meristem and consists of three simple tissues: - Parenchyma (have retained their protoplasm) - Collenchyma (have retained their protoplasm) - Sclerenchyma (have lost their protoplasm in mature stage, i.e. are 'dead') # Parenchyma Parenchyma is the most common ground tissue. It forms, for example, the cortex and pith of stems, the cortex of roots, the mesophyll of leaves, the pulp of fruits, and the endosperm of seeds. Parenchyma cells are still meristematic, which means that they are capable of cell division even after maturation. They have thin but flexible cell walls, and are generally cube-shaped and loosely packed. They have large central vacuoles, which allows the cells to store nutrients and water. Parenchyma cells have a variety of functions: - In leaves, they form the mesophyll and are responsible for photosynthesis and the exchange of gases. - storage - secretion (e.g. Epithelial cells lining the inside of resin ducts) - healing - other specialised functions The form of parenchyma cells varies with their function. The epidermal parenchyma cells of a leaf are barrel shaped and have no chloroplasts. This tissue serves as a barrier wall and protects the internal tissues from injury. In the spongy mesophyll of a leaf, parenchyma cells are spherical and loosely arranged with large intercellular spaces. These cells, with the epidermal guard cells of the stomate, form a system of air spaces and chambers that regulate the exchange of gases. # Collenchyma Collenchyma tissue is composed of elongated cells with unevenly thickened walls. They provide structural support, particularly in growing shoots and leaves. Collenchyma tissue composes, for example, the resilient strands in stalks of celery. Its growth is strongly affected by mechanical stress upon the plant. The walls of collenchyma in shaken (to mimic the effects of wind etc) plants may be 40%-100% thicker than those not shaken. The name collenchyma derives from the Greek word "kolla", meaning "glue", which refers to the thick, glistening appearance of the walls in fresh tissues. There are three principal types of collenchyma: - Angular collenchyma (thickened at intercellular contact points) - Tangential collenchyma (cells arranged into ordered rows and thickened at the tangential face of the cell wall) - Lacunar collenchyma (have intercellular space and thickening proximal to the intercellular space) # Sclerenchyma Sclerenchyma is a supporting tissue. Two groups of sclerenchyma cells exist: fibres and sclereids. Their walls consist of cellulose and lignin. Sclerenchyma cells are the principal supporting cells in plant tissues that have ceased elongation. Sclerenchyma fibres are of great economical importance, since they constitute the source material for many fabrics (flax, hemp, jute, ramie). Unlike the collenchyma, mature sclerenchyma is composed of dead cells with extremely thick cell walls (secondary walls) that make up to 90% of the whole cell volume. The term "sclerenchyma" is derived from the Greek "scleros", meaning "hard". It is their hard, thick walls that make sclerenchyma cells important strengthening and supporting elements in plant parts that have ceased elongation. The difference between fibres and sclereids is not always clear. Transitions do exist, sometimes even within one and the same plant. Fibres are generally long, slender, so-called prosenchymatous cells, usually occurring in strands or bundles. Such bundles or the totality of a stem's bundles are colloquially called fibres. Their high load-bearing capacity and the ease with which they can be processed has since antiquity made them the source material for a number of things, like ropes, fabrics or mattresses. The fibres of flax (Linum usitatissimum) have been known in Europe and Egypt for more than 3000 years, those of hemp (Cannabis sativa) in China for just as long. These fibres, and those of jute (Corchorus capsularis) and ramie (Boehmeria nivea, a nettle), are extremely soft and elastic and are especially well suited for the processing to textiles. Their principal cell wall material is cellulose. Contrasting are hard fibres that are mostly found in monocots. Typical examples are the fibres of many Gramineae, Agaves (sisal: Agave sisalana), lilies (Yucca or Phormium tenax), Musa textilis and others. Their cell walls harbour, besides cellulose, a high proportion of lignin. The load-bearing capacity of Phormium tenax is as high as 20-25 kg/mm2, the same as that of good steel wire (25 kg/ mm2), but the fibre tears as soon as too great a strain is placed upon it, while the wire distorts and tears not before a strain of 80 kg/mm2. The thickening of a cell wall has been studied in Linum. Starting at the centre of the fibre are the thickening layers of the secondary wall deposited one after the other. Growth at both tips of the cell leads to simultaneous elongation. During development the layers of secondary material seem like tubes, of which the outer one is always longer and older than the next. After completion of growth the missing parts are supplemented, so that the wall is evenly thickened up to the tips of the fibres. Fibres stem usually form meristematic tissues. Cambium and procambium are their main centers of production. They are often associated with the xylem of the vascular bundles. The fibres of the xylem are always lignified. Reliable evidence for the fibre cells' evolutionary origin of tracheids exists. During evolution the strength of the cell walls was enhanced, the ability to conduct water was lost and the size of the pits reduced. Fibres that do not belong to the xylem are bast (outside the ring of cambium) and such fibres that are arranged in characteristic patterns at different sites of the shoot. Sclereids are small bundles of sclerenchyma tissue in plants that form durable layers, such as the cores of apples and the gritty texture of pears. Sclereids are variable in shape. The cells can be isodiametric, prosenchymatic, forked or fantastically branched. They can be grouped into bundles, can form complete tubes located at the periphery or can occur as single cells or small groups of cells within parenchyma tissues. But compared with most fibres, sclereids are relatively short. Characteristic examples are the stone cells (called stone cells because of their hardness) of pears (Pyrus communis) and quinces (Cydonia oblonga) and those of the shoot of the wax-plant (Hoya carnosa). The cell walls fill nearly all the cell's volume. A layering of the walls and the existence of branched pits is clearly visible. Branched pits such as these are called ramiform pits. The shell of many seeds like those of nuts as well as the stones of drupes like cherries or plums are made up from sclereids.	Ground tissue The types of ground tissue found in plants develops from ground tissue meristem and consists of three simple tissues: - Parenchyma (have retained their protoplasm) - Collenchyma (have retained their protoplasm) - Sclerenchyma (have lost their protoplasm in mature stage, i.e. are 'dead') # Parenchyma Parenchyma is the most common ground tissue. It forms, for example, the cortex and pith of stems, the cortex of roots, the mesophyll of leaves, the pulp of fruits, and the endosperm of seeds. Parenchyma cells are still meristematic, which means that they are capable of cell division even after maturation. They have thin but flexible cell walls, and are generally cube-shaped and loosely packed. They have large central vacuoles, which allows the cells to store nutrients and water. Parenchyma cells have a variety of functions: - In leaves, they form the mesophyll and are responsible for photosynthesis and the exchange of gases[1]. - storage - secretion (e.g. Epithelial cells lining the inside of resin ducts) - healing - other specialised functions The form of parenchyma cells varies with their function. The epidermal parenchyma cells of a leaf are barrel shaped and have no chloroplasts. This tissue serves as a barrier wall and protects the internal tissues from injury[1]. In the spongy mesophyll of a leaf, parenchyma cells are spherical and loosely arranged with large intercellular spaces[1]. These cells, with the epidermal guard cells of the stomate, form a system of air spaces and chambers that regulate the exchange of gases[1]. # Collenchyma Collenchyma tissue is composed of elongated cells with unevenly thickened walls. They provide structural support, particularly in growing shoots and leaves. Collenchyma tissue composes, for example, the resilient strands in stalks of celery. Its growth is strongly affected by mechanical stress upon the plant. The walls of collenchyma in shaken (to mimic the effects of wind etc) plants may be 40%-100% thicker than those not shaken. The name collenchyma derives from the Greek word "kolla", meaning "glue", which refers to the thick, glistening appearance of the walls in fresh tissues. There are three principal types of collenchyma: - Angular collenchyma (thickened at intercellular contact points) - Tangential collenchyma (cells arranged into ordered rows and thickened at the tangential face of the cell wall) - Lacunar collenchyma (have intercellular space and thickening proximal to the intercellular space) # Sclerenchyma Sclerenchyma is a supporting tissue. Two groups of sclerenchyma cells exist: fibres and sclereids. Their walls consist of cellulose and lignin. Sclerenchyma cells are the principal supporting cells in plant tissues that have ceased elongation. Sclerenchyma fibres are of great economical importance, since they constitute the source material for many fabrics (flax, hemp, jute, ramie). Unlike the collenchyma, mature sclerenchyma is composed of dead cells with extremely thick cell walls (secondary walls) that make up to 90% of the whole cell volume. The term "sclerenchyma" is derived from the Greek "scleros", meaning "hard". It is their hard, thick walls that make sclerenchyma cells important strengthening and supporting elements in plant parts that have ceased elongation. The difference between fibres and sclereids is not always clear. Transitions do exist, sometimes even within one and the same plant. Fibres are generally long, slender, so-called prosenchymatous cells, usually occurring in strands or bundles. Such bundles or the totality of a stem's bundles are colloquially called fibres. Their high load-bearing capacity and the ease with which they can be processed has since antiquity made them the source material for a number of things, like ropes, fabrics or mattresses. The fibres of flax (Linum usitatissimum) have been known in Europe and Egypt for more than 3000 years, those of hemp (Cannabis sativa) in China for just as long. These fibres, and those of jute (Corchorus capsularis) and ramie (Boehmeria nivea, a nettle), are extremely soft and elastic and are especially well suited for the processing to textiles. Their principal cell wall material is cellulose. Contrasting are hard fibres that are mostly found in monocots. Typical examples are the fibres of many Gramineae, Agaves (sisal: Agave sisalana), lilies (Yucca or Phormium tenax), Musa textilis and others. Their cell walls harbour, besides cellulose, a high proportion of lignin. The load-bearing capacity of Phormium tenax is as high as 20-25 kg/mm2, the same as that of good steel wire (25 kg/ mm2), but the fibre tears as soon as too great a strain is placed upon it, while the wire distorts and tears not before a strain of 80 kg/mm2. The thickening of a cell wall has been studied in Linum. Starting at the centre of the fibre are the thickening layers of the secondary wall deposited one after the other. Growth at both tips of the cell leads to simultaneous elongation. During development the layers of secondary material seem like tubes, of which the outer one is always longer and older than the next. After completion of growth the missing parts are supplemented, so that the wall is evenly thickened up to the tips of the fibres. Fibres stem usually form meristematic tissues. Cambium and procambium are their main centers of production. They are often associated with the xylem of the vascular bundles. The fibres of the xylem are always lignified. Reliable evidence for the fibre cells' evolutionary origin of tracheids exists. During evolution the strength of the cell walls was enhanced, the ability to conduct water was lost and the size of the pits reduced. Fibres that do not belong to the xylem are bast (outside the ring of cambium) and such fibres that are arranged in characteristic patterns at different sites of the shoot. Sclereids are small bundles of sclerenchyma tissue in plants that form durable layers, such as the cores of apples and the gritty texture of pears. Sclereids are variable in shape. The cells can be isodiametric, prosenchymatic, forked or fantastically branched. They can be grouped into bundles, can form complete tubes located at the periphery or can occur as single cells or small groups of cells within parenchyma tissues. But compared with most fibres, sclereids are relatively short. Characteristic examples are the stone cells (called stone cells because of their hardness) of pears (Pyrus communis) and quinces (Cydonia oblonga) and those of the shoot of the wax-plant (Hoya carnosa). The cell walls fill nearly all the cell's volume. A layering of the walls and the existence of branched pits is clearly visible. Branched pits such as these are called ramiform pits. The shell of many seeds like those of nuts as well as the stones of drupes like cherries or plums are made up from sclereids.	https://www.wikidoc.org/index.php/Ground_tissue
74245f82c2573813774197b0f75bcc2d7b1c64f0	wikidoc	Growing pains	Growing pains Growing pains are pain symptoms relatively common in children. Typically, they are located in the muscles, rather than the joints, of the leg and less commonly the arm. They are usually felt on both sides, and appear late in the day or at night, wakening the child, with pain varying from mild to very severe. Pain is absent by the morning, and there are no objective clinical signs of inflammation. Pain can recur nightly or be absent for days to months. Growing pain is not associated with other serious disease and usually resolves by late childhood, but frequent episodes are capable of having a substantial effect on the life of the child.. # Diagnosis In the absence of limping, loss of mobility, or physical signs, laboratory investigation to exclude other diagnoses is not warranted. Restless leg syndrome is sometimes misdiagnosed as growing pains. # Epidemiology of growing pains Reported prevalences of growing pains have been between 2% and 46% of children. Growing pains are said to typically occur in two periods during a child's life, firstly, between about 3 and 5 years old, then later in 8 to 12 year olds. There are however no published epidemiological studies to support this observation. # Cause of growing pains The causes of growing pains are unknown. They are not associated with growth spurts and some authors suggest that the term 'recurrent limb pain in childhood' be used instead. Theories of causation include faulty posture, vascular perfusion disorder, tiredness, or psychological causes. Some parents are able to associate episodes of pain with physical exercise or mood changes in the child. # Differential Diagnosis of Growing pains # Treatment Parents and children can be substantially reassured by explaining the benign and self limiting nature of the pains.. There are no substantial studies of the effectiveness of any intervention but local massage or analgesic drugs such as paracetamol are often used. For growing pains in dogs, see panosteitis.	Growing pains Template:DiseaseDisorder infobox Growing pains are pain symptoms relatively common in children. Typically, they are located in the muscles, rather than the joints, of the leg and less commonly the arm. They are usually felt on both sides, and appear late in the day or at night, wakening the child, with pain varying from mild to very severe. Pain is absent by the morning, and there are no objective clinical signs of inflammation. Pain can recur nightly or be absent for days to months. Growing pain is not associated with other serious disease and usually resolves by late childhood, but frequent episodes are capable of having a substantial effect on the life of the child.[1]. # Diagnosis In the absence of limping, loss of mobility, or physical signs, laboratory investigation to exclude other diagnoses is not warranted. [2][1] Restless leg syndrome is sometimes misdiagnosed as growing pains. [2] # Epidemiology of growing pains Reported prevalences of growing pains have been between 2% and 46% of children. [2] Growing pains are said to typically occur in two periods during a child's life, firstly, between about 3 and 5 years old, then later in 8 to 12 year olds.[3] There are however no published epidemiological studies to support this observation. # Cause of growing pains The causes of growing pains are unknown. They are not associated with growth spurts and some authors suggest that the term 'recurrent limb pain in childhood' be used instead.[2] Theories of causation include faulty posture, vascular perfusion disorder, tiredness, or psychological causes.[2] Some parents are able to associate episodes of pain with physical exercise or mood changes in the child.[1] # Differential Diagnosis of Growing pains # Treatment Parents and children can be substantially reassured by explaining the benign and self limiting nature of the pains.[2]. There are no substantial studies of the effectiveness of any intervention but local massage or analgesic drugs such as paracetamol are often used. [1] For growing pains in dogs, see panosteitis.	https://www.wikidoc.org/index.php/Growing_pains
893a8be6ca19567ad38af16fbfb414b3582101b7	wikidoc	Growth factor	Growth factor # Overview The term growth factor refers to a naturally occurring protein capable of stimulating cellular proliferation and cellular differentiation. Growth factors are important for regulating a variety of cellular processes. Growth factors typically act as signaling molecules between cells. Examples are cytokines and hormones that bind to specific receptors on the surface of their target cells. They often promote cell differentiation and maturation, which varies between growth factors. For example, bone morphogenic proteins stimulate bone cell differentiation, while vascular endothelial growth factors stimulate blood vessel differentiation. # Growth factors versus cytokines Growth factor is sometimes used interchangeably among scientists with the term cytokine. Historically, cytokines were associated with hematopoietic (blood forming) cells and immune system cells (e.g., lymphocytes and tissue cells from spleen, thymus, and lymph nodes). For the circulatory system and bone marrow in which cells can occur in a liquid suspension and not bound up in solid tissue, it makes sense for them to communicate by soluble, circulating protein molecules. However, as different lines of research converged, it became clear that some of the same signaling proteins the hematopoietic and immune systems used were also being used by all sorts of other cells and tissues, during development and in the mature organism. While growth factor implies a positive effect on cell division, cytokine is a neutral term with respect to whether a molecule affects proliferation. In this sense, some cytokines can be growth factors, such as G-CSF and GM-CSF. However, some cytokines have an inhibitory effect on cell growth or proliferation. Yet others, such as Fas ligand are used as "death" signals; they cause target cells to undergo programmed cell death or apoptosis. # Example of growth factors Individual growth factor proteins tend to occur as members of larger families of structurally and evolutionarily related proteins. There are dozens and dozens of growth factor families such as TGF-beta (transforming growth factor-beta), BMP (bone morphogenic protein), neurotrophins (NGF, BDNF, and NT3), fibroblast growth factor (FGF), and so on. Several well known growth factors are: - Transforming growth factor beta (TGF-β) - Granulocyte-colony stimulating factor (G-CSF) - Granulocyte-macrophage colony stimulating factor (GM-CSF) - Nerve growth factor (NGF) - Neurotrophins - Platelet-derived growth factor (PDGF) - Erythropoietin (EPO) - Thrombopoietin (TPO) - Myostatin (GDF-8) - Growth differentiation factor-9 (GDF9) - Basic fibroblast growth factor (bFGF or FGF2) - Epidermal growth factor (EGF) - Hepatocyte growth factor (HGF] # Uses in medicine For the last two decades, growth factors have been increasingly used in the treatment of hematologic and oncologic diseases like: - neutropenia - myelodysplastic syndrome (MDS) - leukemias - aplastic anaemia - bone marrow transplantation	Growth factor Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview The term growth factor refers to a naturally occurring protein capable of stimulating cellular proliferation and cellular differentiation. Growth factors are important for regulating a variety of cellular processes. Growth factors typically act as signaling molecules between cells. Examples are cytokines and hormones that bind to specific receptors on the surface of their target cells. They often promote cell differentiation and maturation, which varies between growth factors. For example, bone morphogenic proteins stimulate bone cell differentiation, while vascular endothelial growth factors stimulate blood vessel differentiation. # Growth factors versus cytokines Growth factor is sometimes used interchangeably among scientists with the term cytokine. Historically, cytokines were associated with hematopoietic (blood forming) cells and immune system cells (e.g., lymphocytes and tissue cells from spleen, thymus, and lymph nodes). For the circulatory system and bone marrow in which cells can occur in a liquid suspension and not bound up in solid tissue, it makes sense for them to communicate by soluble, circulating protein molecules. However, as different lines of research converged, it became clear that some of the same signaling proteins the hematopoietic and immune systems used were also being used by all sorts of other cells and tissues, during development and in the mature organism. While growth factor implies a positive effect on cell division, cytokine is a neutral term with respect to whether a molecule affects proliferation. In this sense, some cytokines can be growth factors, such as G-CSF and GM-CSF. However, some cytokines have an inhibitory effect on cell growth or proliferation. Yet others, such as Fas ligand are used as "death" signals; they cause target cells to undergo programmed cell death or apoptosis. # Example of growth factors Individual growth factor proteins tend to occur as members of larger families of structurally and evolutionarily related proteins. There are dozens and dozens of growth factor families such as TGF-beta (transforming growth factor-beta), BMP (bone morphogenic protein), neurotrophins (NGF, BDNF, and NT3), fibroblast growth factor (FGF), and so on. Several well known growth factors are: - Transforming growth factor beta (TGF-β) - Granulocyte-colony stimulating factor (G-CSF) - Granulocyte-macrophage colony stimulating factor (GM-CSF) - Nerve growth factor (NGF) - Neurotrophins - Platelet-derived growth factor (PDGF) - Erythropoietin (EPO) - Thrombopoietin (TPO) - Myostatin (GDF-8) - Growth differentiation factor-9 (GDF9) - Basic fibroblast growth factor (bFGF or FGF2) - Epidermal growth factor (EGF) - Hepatocyte growth factor (HGF] # Uses in medicine For the last two decades, growth factors have been increasingly used in the treatment of hematologic and oncologic diseases like: - neutropenia - myelodysplastic syndrome (MDS) - leukemias - aplastic anaemia - bone marrow transplantation	https://www.wikidoc.org/index.php/Growth_Factor
1e20d7268709b61ff02ffe0d0f0d3c9a0833eac6	wikidoc	Guidewire tip	Guidewire tip # Overview The tip of the coronary guidewire plays a critical role in determining the pushability, the steering, the tactile feel and torquability of the wire. There are two general types of guidewire tips; a tip coil which is flexible in shippable and is often used in workhorse wires, and an A-tip in which the guidewire core extends all the way to the tip of the guidewire yielding a stiffer and more torquable tip which comes at the risk of vessel perforation # Characterizing the Physical Characteristics of a Coronary Guidewire Using the Tip Load One way of quantifying some of the physical features of a coronary guidewire is by using a strain gauge to measure the force needed to bend a wire when exerted on a straight guidewire tip, at a point 1 cm from the tip. Using this method, the tip loads in ascending order are (from less stiff to more stiff) 3 gm, 4.5 gm, 6 gm, 9 gm and 12 gm (ultra stiff). As stiffness increases the wire becomes prone to perforating the vessel. # Determinants of Tip Flexibility There can be one or more joints made of different materials in the tips of guidewires. The number of joints and the nature of the joints can influence the clinical performance of the wires. These joints can serve as hinge points and bend during guidewire passage. # Core-to-tip Guidewires When the core is extended to the tip, that increases pushability, precise steering, tip control, tactile feel and torquability. This can be a useful feature for example in probing chronic total occlusions. If there is a two piece tip to the guidewire, then shaping is easy and the wire is likely to retain its shape, a property called “wire memory”. # Shaping Ribbon Incorporation of a shaping tip yields a softer tip that allows for shape retention. # Spring Coil Tip A spring coil tip may improve the performance of coronary guidewires. These tips are safer than hydrophilic coated or polymer tip wires and are associated with a lower risk of perforation. # Tip Cover The tip can be covered in either a polymer or plastic. This covering can provide either lubricity or smooth tracking through vessel tortuosity. A polymer cover instead of a spring coil with hydrophilic coating may improve guidewire trackability but may reduce tactile feedback / feel. Examples of this design are the PT Graphix™ Intermediate Guide Wire, and the ChoICE PT wire. # ”Combination” Tips There are several types of combination tips available: - Tip coils plus - Intermediate coils - Bare core - Plastic cover - Polymer - Polymer over tip coils	Guidewire tip Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] To go back to the main page on Guidewires, click here. # Overview The tip of the coronary guidewire plays a critical role in determining the pushability, the steering, the tactile feel and torquability of the wire. There are two general types of guidewire tips; a tip coil which is flexible in shippable and is often used in workhorse wires, and an A-tip in which the guidewire core extends all the way to the tip of the guidewire yielding a stiffer and more torquable tip which comes at the risk of vessel perforation # Characterizing the Physical Characteristics of a Coronary Guidewire Using the Tip Load One way of quantifying some of the physical features of a coronary guidewire is by using a strain gauge to measure the force needed to bend a wire when exerted on a straight guidewire tip, at a point 1 cm from the tip. Using this method, the tip loads in ascending order are (from less stiff to more stiff) 3 gm, 4.5 gm, 6 gm, 9 gm and 12 gm (ultra stiff). As stiffness increases the wire becomes prone to perforating the vessel. # Determinants of Tip Flexibility There can be one or more joints made of different materials in the tips of guidewires. The number of joints and the nature of the joints can influence the clinical performance of the wires. These joints can serve as hinge points and bend during guidewire passage. # Core-to-tip Guidewires When the core is extended to the tip, that increases pushability, precise steering, tip control, tactile feel and torquability. This can be a useful feature for example in probing chronic total occlusions. If there is a two piece tip to the guidewire, then shaping is easy and the wire is likely to retain its shape, a property called “wire memory”. # Shaping Ribbon Incorporation of a shaping tip yields a softer tip that allows for shape retention. # Spring Coil Tip A spring coil tip may improve the performance of coronary guidewires. These tips are safer than hydrophilic coated or polymer tip wires and are associated with a lower risk of perforation. # Tip Cover The tip can be covered in either a polymer or plastic. This covering can provide either lubricity or smooth tracking through vessel tortuosity. A polymer cover instead of a spring coil with hydrophilic coating may improve guidewire trackability but may reduce tactile feedback / feel. Examples of this design are the PT Graphix™ Intermediate Guide Wire, and the ChoICE PT wire. # ”Combination” Tips There are several types of combination tips available: - Tip coils plus - Intermediate coils - Bare core - Plastic cover - Polymer - Polymer over tip coils	https://www.wikidoc.org/index.php/Guidewire_Tip
89b12030e98586f26391fdfbfd3a0a0c0c7670f4	wikidoc	H1 antagonist	H1 antagonist An H1 antagonist is a histamine antagonist of the H1 receptor that serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions. Agents where the main therapeutic effect is mediated by negative modulation of histamine receptors are termed antihistamines - other agents may have antihistaminergic action but are not true antihistamines. In common use, the term "antihistamine" refers only to H1 antagonists, also known as H1-receptor antagonists and H1-antihistamines. It has been discovered that these H1-antihistamines are actually inverse agonists at the histamine H1-receptor, rather than antagonists per se. # Pharmacology In allergic reactions, an allergen (a type of antigen) interacts with and cross-links surface IgE antibodies on mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H1-receptors, produces pruritus, vasodilatation, hypotension, flushing, headache, tachycardia, bronchoconstriction, increase in vascular permeability, potentiation of pain, and more. While H1-antihistamines help against these effects, they work only if taken before contact with the allergen. In severe allergies, such as anaphylaxis or angioedema, these effects may be so severe as to be life-threatening. Additional administration of epinephrine, often in the form of an autoinjector (Epi-pen), is required by people with such hypersensitivities. # Clinical use of H1-antihistamines ## Indications H1-antihistamines are clinically used in the treatment of histamine-mediated allergic conditions. Specifically, these indications may include: - Allergic rhinitis - Allergic conjunctivitis - Allergic dermatological conditions (contact dermatitis) - Urticaria - Angioedema - Diarrhea - Pruritus (atopic dermatitis, insect bites) - Anaphylactic or anaphylactoid reactions - adjunct only - Nausea and vomiting (first-generation H1-antihistamines) - Sedation (first-generation H1-antihistamines) H1-antihistamines can be administered topically (through the skin, nose, or eyes) or systemically, based on the nature of the allergic condition. The authors of the American College of Chest Physicians Updates on Cough Guidelines (2006) recommend that, for cough associated with the common cold, first-generation antihistamine-decongestants are more effective than newer, non-sedating antihistamines. First-generation antihistamines include diphenhydramine (Benadryl); carbinoxamine (Clistin); clemastine (Tavist); chlorpheniramine (Chlor-Trimeton) and brompheniramine (Dimetane). However, it is important to note that a 1955 study of "antihistaminic drugs for colds," carried out by the U.S. Army Medical Corps, reported that "there was no significant difference in the proportion of cures reported by patients receiving oral antihistaminic drugs and those receiving oral placebos. Furthermore, essentially the same proportion of patients reported no benefit from either type of treatment." ## Adverse drug reactions Adverse drug reactions are most commonly associated with the first-generation H1-antihistamines. This is due to their relative lack of selectivity for the H1-receptor. The most common adverse effect is sedation; this "side-effect" is utilized in many OTC sleeping-aid preparations. Other common adverse effects in first-generation H1-antihistamines include dizziness, tinnitus, blurred vision, euphoria, uncoordination, anxiety, insomnia, tremor, nausea and vomiting, constipation, diarrhea, dry mouth, and dry cough. Infrequent adverse effects include urinary retention, palpitations, hypotension, headache, hallucination, and psychosis. The newer second-generation H1-antihistamines are far more selective for peripheral histamine H1-receptors and have a far improved tolerability profile compared to the first-generation agents. The most common adverse effects noted for second-generation agents include drowsiness, fatigue, headache, nausea and dry mouth. # First-generation (non-selective, classical) These are the oldest H1-antihistaminergic drugs and are relatively inexpensive and widely available. They are effective in the relief of allergic symptoms, but are typically moderately to highly-potent muscarinic acetylcholine receptor-antagonists (anticholinergic) agents as well. These agents also commonly have action at α-adrenergic receptors and/or 5-HT receptors. This lack of receptor-selectivity is the basis of the poor tolerability-profile of some of these agents, especially compared with the second-generation H1-antihistamines. Patient response and occurrence of adverse drug reactions vary greatly between classes and between agents within classes. ## Classes The first H1-antihistamine discovered was piperoxan, by Ernest Fourneau and Daniel Bovet (1933) in their efforts to develop a guinea pig animal-model for anaphylaxis at Ryerson University. Bovet went on to win the 1957 Nobel Prize in Physiology or Medicine for his contribution. Following their discovery, the first-generation H1-antihistamines were developed in the following decades. They can be classified on the basis of chemical structure, and agents within these groups have similar properties. ## Common structural features - Two aromatic rings, connected to a central carbon, nitrogen or CO - Spacer between the central X and the amine, usually 2-3 carbons in length, linear, ring, branched, saturated or unsaturated - Amine is substituted with small alkyl groups, e.g., CH3 X = N, R1 = R2 = small alkyl groups X = C X = CO - Chirality at X can increase both the potency and selectivity for H1-receptors - For maximum potency, the two aromatic rings should be orientated in different planes for example, tricyclic ring system is slightly puckered and the two aromatic rings lie in different geometrical planes, giving the drug a very high potency. - for example, tricyclic ring system is slightly puckered and the two aromatic rings lie in different geometrical planes, giving the drug a very high potency. # Second-generation and third-generation (selective, non-sedating) Second generation H1-antihistamines are newer drugs that are much more selective for peripheral H1 receptors in preference to the central nervous system histaminergic and cholinergic receptors. This selectivity significantly reduces the occurrence of adverse drug reactions compared with first-generation agents, while still providing effective relief of allergic conditions. Third-generation H1-antihistamines are the active enantiomer (levocetirizine) or metabolite (desloratadine & fexofenadine) derivatives of second-generation drugs intended to have increased efficacy with fewer adverse drug reactions. Indeed, fexofenadine is associated with a decreased risk of cardiac arrhythmia compared to terfenadine. However, there is little evidence for any advantage of levocetirizine or desloratadine, compared to cetirizine or loratadine, respectively. ## Systemic, second-generation - Acrivastine - Astemizole - Cetirizine - Loratadine - Mizolastine - Terfenadine ## Topical, second-generation - Azelastine - Levocabastine - Olopatadine ## Systemic, third-generation - Levocetirizine - Desloratadine - Fexofenadine ## Common structural features Structure of these drugs varies from case to case. There are no common structural features.	H1 antagonist Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Template:Downsize An H1 antagonist is a histamine antagonist of the H1 receptor that serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions. Agents where the main therapeutic effect is mediated by negative modulation of histamine receptors are termed antihistamines - other agents may have antihistaminergic action but are not true antihistamines. In common use, the term "antihistamine" refers only to H1 antagonists, also known as H1-receptor antagonists and H1-antihistamines. It has been discovered that these H1-antihistamines are actually inverse agonists at the histamine H1-receptor, rather than antagonists per se. [1] # Pharmacology In allergic reactions, an allergen (a type of antigen) interacts with and cross-links surface IgE antibodies on mast cells and basophils. Once the mast cell-antibody-antigen complex is formed, a complex series of events occurs that eventually leads to cell degranulation and the release of histamine (and other chemical mediators) from the mast cell or basophil. Once released, histamine can react with local or widespread tissues through histamine receptors. Histamine, acting on H1-receptors, produces pruritus, vasodilatation, hypotension, flushing, headache, tachycardia, bronchoconstriction, increase in vascular permeability, potentiation of pain, and more. [2] While H1-antihistamines help against these effects, they work only if taken before contact with the allergen. In severe allergies, such as anaphylaxis or angioedema, these effects may be so severe as to be life-threatening. Additional administration of epinephrine, often in the form of an autoinjector (Epi-pen), is required by people with such hypersensitivities. # Clinical use of H1-antihistamines ## Indications H1-antihistamines are clinically used in the treatment of histamine-mediated allergic conditions. Specifically, these indications may include: [3] - Allergic rhinitis - Allergic conjunctivitis - Allergic dermatological conditions (contact dermatitis) - Urticaria - Angioedema - Diarrhea - Pruritus (atopic dermatitis, insect bites) - Anaphylactic or anaphylactoid reactions - adjunct only - Nausea and vomiting (first-generation H1-antihistamines) - Sedation (first-generation H1-antihistamines) H1-antihistamines can be administered topically (through the skin, nose, or eyes) or systemically, based on the nature of the allergic condition. The authors of the American College of Chest Physicians Updates on Cough Guidelines (2006) recommend that, for cough associated with the common cold, first-generation antihistamine-decongestants are more effective than newer, non-sedating antihistamines. First-generation antihistamines include diphenhydramine (Benadryl); carbinoxamine (Clistin); clemastine (Tavist); chlorpheniramine (Chlor-Trimeton) and brompheniramine (Dimetane). However, it is important to note that a 1955 study of "antihistaminic drugs for colds," carried out by the U.S. Army Medical Corps, reported that "there was no significant difference in the proportion of cures reported by patients receiving oral antihistaminic drugs and those receiving oral placebos. Furthermore, essentially the same proportion of patients reported no benefit from either type of treatment."[4] ## Adverse drug reactions Adverse drug reactions are most commonly associated with the first-generation H1-antihistamines. This is due to their relative lack of selectivity for the H1-receptor. The most common adverse effect is sedation; this "side-effect" is utilized in many OTC sleeping-aid preparations. Other common adverse effects in first-generation H1-antihistamines include dizziness, tinnitus, blurred vision, euphoria, uncoordination, anxiety, insomnia, tremor, nausea and vomiting, constipation, diarrhea, dry mouth, and dry cough. Infrequent adverse effects include urinary retention, palpitations, hypotension, headache, hallucination, and psychosis. [3] The newer second-generation H1-antihistamines are far more selective for peripheral histamine H1-receptors and have a far improved tolerability profile compared to the first-generation agents. The most common adverse effects noted for second-generation agents include drowsiness, fatigue, headache, nausea and dry mouth. [3] # First-generation (non-selective, classical) These are the oldest H1-antihistaminergic drugs and are relatively inexpensive and widely available. They are effective in the relief of allergic symptoms, but are typically moderately to highly-potent muscarinic acetylcholine receptor-antagonists (anticholinergic) agents as well. These agents also commonly have action at α-adrenergic receptors and/or 5-HT receptors. This lack of receptor-selectivity is the basis of the poor tolerability-profile of some of these agents, especially compared with the second-generation H1-antihistamines. Patient response and occurrence of adverse drug reactions vary greatly between classes and between agents within classes. ## Classes The first H1-antihistamine discovered was piperoxan, by Ernest Fourneau and Daniel Bovet (1933) in their efforts to develop a guinea pig animal-model for anaphylaxis at Ryerson University.[5] Bovet went on to win the 1957 Nobel Prize in Physiology or Medicine for his contribution. Following their discovery, the first-generation H1-antihistamines were developed in the following decades. They can be classified on the basis of chemical structure, and agents within these groups have similar properties. ## Common structural features - Two aromatic rings, connected to a central carbon, nitrogen or CO - Spacer between the central X and the amine, usually 2-3 carbons in length, linear, ring, branched, saturated or unsaturated - Amine is substituted with small alkyl groups, e.g., CH3 X = N, R1 = R2 = small alkyl groups X = C X = CO - Chirality at X can increase both the potency and selectivity for H1-receptors - For maximum potency, the two aromatic rings should be orientated in different planes for example, tricyclic ring system is slightly puckered and the two aromatic rings lie in different geometrical planes, giving the drug a very high potency. - for example, tricyclic ring system is slightly puckered and the two aromatic rings lie in different geometrical planes, giving the drug a very high potency. # Second-generation and third-generation (selective, non-sedating) Second generation H1-antihistamines are newer drugs that are much more selective for peripheral H1 receptors in preference to the central nervous system histaminergic and cholinergic receptors. This selectivity significantly reduces the occurrence of adverse drug reactions compared with first-generation agents, while still providing effective relief of allergic conditions. Third-generation H1-antihistamines are the active enantiomer (levocetirizine) or metabolite (desloratadine & fexofenadine) derivatives of second-generation drugs intended to have increased efficacy with fewer adverse drug reactions. Indeed, fexofenadine is associated with a decreased risk of cardiac arrhythmia compared to terfenadine. However, there is little evidence for any advantage of levocetirizine or desloratadine, compared to cetirizine or loratadine, respectively. ## Systemic, second-generation - Acrivastine - Astemizole - Cetirizine - Loratadine - Mizolastine - Terfenadine ## Topical, second-generation - Azelastine - Levocabastine - Olopatadine ## Systemic, third-generation - Levocetirizine - Desloratadine - Fexofenadine ## Common structural features Structure of these drugs varies from case to case. There are no common structural features.	https://www.wikidoc.org/index.php/H1-receptor_antagonist
6ed0a0c6188cda749c7a4f6aa7436b0cfac1a339	wikidoc	H2 antagonist	H2 antagonist An H2-receptor antagonist, (H2RA) shortened to H2 antagonist, is a classification of drugs used to block the action of histamine on parietal cells in the stomach, decreasing acid production by these cells. These drugs are used in the treatment of dyspepsia; however, their use has waned since the advent of the more effective proton pump inhibitors. Like the H1-antihistamines, the H2 antagonists are inverse agonists rather than true receptor antagonists. # History and development Cimetidine was the prototypical histamine H2-receptor antagonist from which the later members of the class were developed. Cimetidine was the culmination of a project at Smith, Kline & French (SK&F; now GlaxoSmithKline) to develop a histamine receptor antagonist to suppress stomach acid secretion. In 1964 it was known that histamine was able to stimulate the secretion of stomach acid, but also that traditional antihistamines had no effect on acid production. From these facts the SK&F scientists postulated the existence of two histamine receptors. They designated the one acted on by the traditional antihistamines H1, and the one acted on by histamine to stimulate the secretion of stomach acid H2. The SK&F team used a rational drug design process starting from the structure of histamine - the only design lead, since nothing was known of the then hypothetical H2 receptor. Hundreds of modified compounds were synthesized in an effort to develop a model of the receptor. The first breakthrough was Nα-guanylhistamine, a partial H2-receptor antagonist. From this lead the receptor model was further refined and eventually led to the development of burimamide - the first H2-receptor antagonist. Burimamide, a specific competitive antagonist at the H2 receptor 100-times more potent than Nα-guanylhistamine, proved the existence of the H2 receptor. Burimamide was still insufficiently potent for oral administration and further modification of the structure, based on modifying the pKa of the compound, lead to the development of metiamide. Metiamide was an effective agent; however, it was associated with unacceptable nephrotoxicity and agranulocytosis. It was proposed that the toxicity arose from the thiourea group, and similar guanidine-analogues were investigated until the ultimate discovery of Cimetidine (common brand name Tagamet). Ranitidine (common brand name Zantac) was developed by Glaxo (also now GlaxoSmithKline) in an effort to match the success of Smith, Kline & French with cimetidine. Ranitidine was also the result of a rational drug design process utilizing the by-then-fairly-refined model of the histamine H2 receptor and quantitative structure-activity relationships (QSAR). Glaxo refined the model further by replacing the imidazole-ring of cimetidine with a furan-ring with a nitrogen-containing substituent, and in doing so developed ranitidine. Ranitidine was found to have a far-improved tolerability profile (i.e. fewer adverse drug reactions), longer-lasting action, and ten times the activity of cimetidine. Ranitidine was introduced in 1981 and was the world's biggest-selling prescription drug by 1988. The H2-receptor antagonists have since largely been superseded by the even more effective proton pump inhibitors, with omeprazole becoming the biggest-selling drug for many years. # Pharmacology The H2 antagonists are competitive inhibitors of histamine at the parietal cell H2 receptor. They suppress the normal secretion of acid by parietal cells and the meal-stimulated secretion of acid. They accomplish this by two mechanisms: histamine released by ECL cells in the stomach is blocked from binding on parietal cell H2 receptors which stimulate acid secretion, and other substances that promote acid secretion (such as gastrin and acetylcholine) have a reduced effect on parietal cells when the H2 receptors are blocked. # Clinical use of H2-antagonists ## Indications H2-Antagonists are clinically used in the treatment of acid-related Gastrointestinal conditions. Specifically, these indications may include: - Peptic Ulcer Disease (PUD) - Gastroesophageal Reflux Disease (GERD) - Dyspepsia - Stress Ulcer Prophylaxis (Ranitidine) People that suffer from heartburn (GERD) infrequently may take either antacids or H2-receptor antagonists for treatment. H2-antagonists offer several advantages over antacids including longer duration of action (6–10 hours vs 1–2 hours for antacids), greater efficacy, and ability to be used prophylactically before meals to reduce the chance of heartburn occurring. Proton pump inhibitors, however, are the preferred treatment for erosive esophagitis since they have been shown to promote healing better than H2-antagonists. Some studies also suggest that H2-antagonists might be effective in treating herpes viruses, such as shingles and herpes simplex . ## Adverse drug reactions H2 antagonists are generally well-tolerated, except for cimetidine where all of the following adverse drug reactions (ADRs) are common. Infrequent ADRs include hypotension. Rare ADRs include: headache, tiredness, dizziness, confusion, diarrhoea, constipation, and rash. Additionally, cimetidine may also cause gynecomastia in males, loss of libido, and impotence, which are reversible upon discontinuation. ## Drug interactions With regard to pharmacokinetics, cimetidine in particular interferes with some of the body's mechanisms of drug metabolism and elimination through the liver cytochrome P450 pathway. Specifically, cimetidine is an inhibitor of the P450 enzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4. By reducing the metabolism of drugs through these enzymes, cimetidine may increase their serum concentrations to toxic levels. Examples of drugs affected include: warfarin, theophylline, phenytoin, lidocaine, quinidine, propranolol, labetalol, metoprolol, tricyclic antidepressants, some benzodiazepines, dihydropyridine calcium channel blockers, sulfonylureas, metronidazole, and some recreational drugs such as ethanol and MDMA. The more recently developed H2-receptor antagonists, such as famotidine, are much less likely to alter CYP metabolism. # Examples Cimetidine was the prototypical member of the H2 antagonists. Further developments, using quantitative structure-activity relationships (QSAR) led to the development of further agents with improved tolerability-profiles. In the United States, all four members of the group are available over the counter in relatively low doses, and have become extremely popular medications marketed to heartburn sufferers. - cimetidine (Tagamet) - ranitidine (Zantac) - famotidine (Pepcid) - nizatidine (Axid, Tazac)	H2 antagonist Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] An H2-receptor antagonist, (H2RA) shortened to H2 antagonist, is a classification of drugs used to block the action of histamine on parietal cells in the stomach, decreasing acid production by these cells. These drugs are used in the treatment of dyspepsia; however, their use has waned since the advent of the more effective proton pump inhibitors. Like the H1-antihistamines, the H2 antagonists are inverse agonists rather than true receptor antagonists. # History and development Cimetidine was the prototypical histamine H2-receptor antagonist from which the later members of the class were developed. Cimetidine was the culmination of a project at Smith, Kline & French (SK&F; now GlaxoSmithKline) to develop a histamine receptor antagonist to suppress stomach acid secretion. In 1964 it was known that histamine was able to stimulate the secretion of stomach acid, but also that traditional antihistamines had no effect on acid production. From these facts the SK&F scientists postulated the existence of two histamine receptors. They designated the one acted on by the traditional antihistamines H1, and the one acted on by histamine to stimulate the secretion of stomach acid H2. The SK&F team used a rational drug design process starting from the structure of histamine - the only design lead, since nothing was known of the then hypothetical H2 receptor. Hundreds of modified compounds were synthesized in an effort to develop a model of the receptor. The first breakthrough was Nα-guanylhistamine, a partial H2-receptor antagonist. From this lead the receptor model was further refined and eventually led to the development of burimamide - the first H2-receptor antagonist. Burimamide, a specific competitive antagonist at the H2 receptor 100-times more potent than Nα-guanylhistamine, proved the existence of the H2 receptor. Burimamide was still insufficiently potent for oral administration and further modification of the structure, based on modifying the pKa of the compound, lead to the development of metiamide. Metiamide was an effective agent; however, it was associated with unacceptable nephrotoxicity and agranulocytosis. It was proposed that the toxicity arose from the thiourea group, and similar guanidine-analogues were investigated until the ultimate discovery of Cimetidine (common brand name Tagamet). Ranitidine (common brand name Zantac) was developed by Glaxo (also now GlaxoSmithKline) in an effort to match the success of Smith, Kline & French with cimetidine. Ranitidine was also the result of a rational drug design process utilizing the by-then-fairly-refined model of the histamine H2 receptor and quantitative structure-activity relationships (QSAR). Glaxo refined the model further by replacing the imidazole-ring of cimetidine with a furan-ring with a nitrogen-containing substituent, and in doing so developed ranitidine. Ranitidine was found to have a far-improved tolerability profile (i.e. fewer adverse drug reactions), longer-lasting action, and ten times the activity of cimetidine. Ranitidine was introduced in 1981 and was the world's biggest-selling prescription drug by 1988. The H2-receptor antagonists have since largely been superseded by the even more effective proton pump inhibitors, with omeprazole becoming the biggest-selling drug for many years. # Pharmacology The H2 antagonists are competitive inhibitors of histamine at the parietal cell H2 receptor. They suppress the normal secretion of acid by parietal cells and the meal-stimulated secretion of acid. They accomplish this by two mechanisms: histamine released by ECL cells in the stomach is blocked from binding on parietal cell H2 receptors which stimulate acid secretion, and other substances that promote acid secretion (such as gastrin and acetylcholine) have a reduced effect on parietal cells when the H2 receptors are blocked. # Clinical use of H2-antagonists ## Indications H2-Antagonists are clinically used in the treatment of acid-related Gastrointestinal conditions. Specifically, these indications may include:[1] - Peptic Ulcer Disease (PUD) - Gastroesophageal Reflux Disease (GERD) - Dyspepsia - Stress Ulcer Prophylaxis (Ranitidine) People that suffer from heartburn (GERD) infrequently may take either antacids or H2-receptor antagonists for treatment. H2-antagonists offer several advantages over antacids including longer duration of action (6–10 hours vs 1–2 hours for antacids), greater efficacy, and ability to be used prophylactically before meals to reduce the chance of heartburn occurring. Proton pump inhibitors, however, are the preferred treatment for erosive esophagitis since they have been shown to promote healing better than H2-antagonists. Some studies also suggest that H2-antagonists might be effective in treating herpes viruses, such as shingles and herpes simplex [2]. ## Adverse drug reactions H2 antagonists are generally well-tolerated, except for cimetidine where all of the following adverse drug reactions (ADRs) are common. Infrequent ADRs include hypotension. Rare ADRs include: headache, tiredness, dizziness, confusion, diarrhoea, constipation, and rash.[1] Additionally, cimetidine may also cause gynecomastia in males, loss of libido, and impotence, which are reversible upon discontinuation. ## Drug interactions With regard to pharmacokinetics, cimetidine in particular interferes with some of the body's mechanisms of drug metabolism and elimination through the liver cytochrome P450 pathway. Specifically, cimetidine is an inhibitor of the P450 enzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4. By reducing the metabolism of drugs through these enzymes, cimetidine may increase their serum concentrations to toxic levels. Examples of drugs affected include: warfarin, theophylline, phenytoin, lidocaine, quinidine, propranolol, labetalol, metoprolol, tricyclic antidepressants, some benzodiazepines, dihydropyridine calcium channel blockers, sulfonylureas, metronidazole, and some recreational drugs such as ethanol and MDMA. The more recently developed H2-receptor antagonists, such as famotidine, are much less likely to alter CYP metabolism.[2] # Examples Cimetidine was the prototypical member of the H2 antagonists. Further developments, using quantitative structure-activity relationships (QSAR) led to the development of further agents with improved tolerability-profiles. In the United States, all four members of the group are available over the counter in relatively low doses, and have become extremely popular medications marketed to heartburn sufferers. - cimetidine (Tagamet) - ranitidine (Zantac) - famotidine (Pepcid) - nizatidine (Axid, Tazac)	https://www.wikidoc.org/index.php/H2
393a6b365dec94191d735df42f164e9ff8076c7b	wikidoc	Haber process	Haber process # Overview The Haber process, also called the Haber–Bosch process, is the reaction of nitrogen and hydrogen, over an iron substrate, to produce ammonia. The Haber process is important because ammonia is difficult to produce on an industrial scale. Even though 78.1% of the air we breathe is nitrogen, the gas is relatively unreactive because nitrogen molecules are held together by strong triple bonds. It was not until the early 20th century that this method was developed to harness the atmospheric abundance of nitrogen to create ammonia, which can then be oxidized to make the nitrates and nitrites essential for the production of nitrate fertilizer and munitions. # History The process was first patented by Fritz Haber. In 1910 Carl Bosch, while working for chemical company BASF, successfully commercialized the process and secured further patents. Haber and Bosch were later awarded Nobel prizes, in 1918 and 1931 respectively, for their work in overcoming the chemical and engineering problems posed by the use of large-scale high-pressure technology. Ammonia was first manufactured using the Haber process on an industrial scale in Germany during World War I to meet the high demand for ammonium nitrate (for use in explosives) at a time when supply of Chile saltpetre from Chile could not be guaranteed because this industry was then almost 100% in British hands. It has been suggested that without this process, Germany would almost certainly have run out of explosives by 1916, thereby ending the war. # The process The bulk of the chemical technology consists in getting the hydrogen from methane or natural gas using heterogeneous catalysis and then reacting it with the atmospheric nitrogen. ## Synthesis gas preparation First, the methane is cleaned, mainly to remove sulfur impurities that would poison the catalysts. This is done by turning sulfur into hydrogen sulfide: and then reacting with zinc oxide to form zinc sulfide: The clean methane is then reacted with steam over a catalyst of nickel oxide. This is called steam reforming: Secondary reforming then takes place with the addition of air to convert the methane that did not react during steam reforming. The carbon monoxide formed is also cause catalyst poisoning, which would react with the iron catalyst, forming an iron compound, thus affecting the reaction. The air added during this step also serves as a nitrogen source for ammonia synthesis: Then occur two’’shifts’’ which convert CO to CO2 by reaction with steam, one at high temperature, then one at low temperature: Then the carbon dioxide is removed by reaction with potassium carbonate. The gas mixture is now passed into a methanator which converts any remaining CO2 into methane for recycling: We now have a gas mixture containing nitrogen and hydrogen in the correct ratio of 1:3. ## Ammonia synthesis The final stage is the crucial synthesis of ammonia using promoted magnetite, iron oxide, as the catalyst: This is done at 150 - 250 atmospheres (atm) and between 300 and 550 °C, passing the gases over four beds of catalyst, with cooling between each pass to maintain a reasonable equilibrium constant. On each pass only about 15% conversion occurs, but any unreacted gases will be recycled, so that eventually an overall yield of 98% can be achieved. # Reaction Rate and Equilibrium There are two opposing considerations in this synthesis: the position of the equilibrium and the rate of reaction. At room temperature, the reaction is slow and the obvious solution is to raise the temperature. This may increase the rate of the reaction but, since the reaction is exothermic, it also has the effect, according to Le Chatelier's Principle, of favouring the reverse reaction and thus reducing equilibrium constant, given by: K_\mathrm{eq} = \mathrm{\frac{^2}{^3}} As the temperature increases, the equilibrium is shifted and hence, the constant drops dramatically according to the van't Hoff equation. Thus one might suppose that a low temperature is to be used and some other means to increase rate. However, the catalyst itself requires a temperature of at least 400 °C to be efficient. Pressure is the obvious choice to favour the forward reaction because there are 4 moles of reactant for every 2 moles of product, and the pressure used (around 200 atm) alters the equilibrium concentrations to give a profitable yield. Economically, though, pressure is an expensive commodity. Pipes and reaction vessels need to be strengthened, valves more rigorous, and there are safety considerations of working at 200 atm. In addition, running pumps and compressors takes considerable energy. Thus the compromise used gives a single pass yield of around 15%. Another way to increase the yield of the reaction would be to remove the product (i.e. ammonia gas) from the system. In practice, gaseous ammonia is not removed from the reactor itself, since the temperature is too high; but it is removed from the equilibrium mixture of gases leaving the reaction vessel. The hot gases are cooled enough, whilst maintaining a high pressure, for the ammonia to condense and be removed as liquid. Unreacted hydrogen and nitrogen gases are then returned to the reaction vessel to undergo further reaction. # Catalysts The catalyst has no effect on the position of equilibrium, rather, it provides an alternative pathway with lower activation energy and hence increases the reaction rate, while remaining chemically unchanged at the end of the reaction. The first Haber–Bosch reaction chambers used osmium and uranium catalysts. However, today a much less expensive iron catalyst is used almost exclusively. In industrial practice, the iron catalyst is prepared by exposing a mass of magnetite, an iron oxide, to the hot hydrogen feedstock. This reduces some of the magnetite to metallic iron, removing oxygen in the process. However, the catalyst maintains most of its bulk volume during the reduction, and so the result is a highly porous material whose large surface area aids its effectiveness as a catalyst. Other minor components of the catalyst include calcium and aluminium oxides, which support the porous iron catalyst and help it maintain its surface area over time, and potassium, which increases the electron density of the catalyst and so improves its reactivity. The reaction mechanism, involving the heterogeneous catalyst, is believed to be as follows: - N2(g) → N2(adsorbed) - N2(adsorbed) → 2N(adsorbed) - H2(g) → H2(adsorbed) - H2(adsorbed) → 2H(adsorbed) - N(adsorbed) + 3H(adsorbed)→ NH3(adsorbed) - NH3(adsorbed) → NH3(g) Reaction 5 occurs in three steps, forming NH, NH2, and then NH3. Experimental evidence points to reaction 2 as being the slow, rate-determining step. A major contributor to the elucidation of this mechanism is Gerhard Ertl. # Economic and environmental aspects The Haber process now produces 100 million tons of nitrogen fertilizer per year, mostly in the form of anhydrous ammonia, ammonium nitrate, and urea. 3-5% of world natural gas production is consumed in the Haber process (~1-2% of the world's annual energy supply),,,. That fertilizer is responsible for sustaining one-third of the Earth's population, as well as various deleterious environmental consequences. Generation of hydrogen using electrolysis of water, using renewable energy, is not currently competitive cost-wise with hydrogen from fossil fuels, such as natural gas, and is responsible for only 4% of current hydrogen production. Notably, the rise of this industrial process led to the "Nitrate Crisis" in Chile, when the British industrials left the country -- since the natural nitrate mines were no longer profitable -- closing the mines and leaving a large unemployed Chilean population behind.	Haber process # Overview The Haber process, also called the Haber–Bosch process, is the reaction of nitrogen and hydrogen, over an iron substrate, to produce ammonia.[1][2][3] The Haber process is important because ammonia is difficult to produce on an industrial scale. Even though 78.1% of the air we breathe is nitrogen, the gas is relatively unreactive because nitrogen molecules are held together by strong triple bonds. It was not until the early 20th century that this method was developed to harness the atmospheric abundance of nitrogen to create ammonia, which can then be oxidized to make the nitrates and nitrites essential for the production of nitrate fertilizer and munitions. # History The process was first patented by Fritz Haber. In 1910 Carl Bosch, while working for chemical company BASF, successfully commercialized the process and secured further patents. Haber and Bosch were later awarded Nobel prizes, in 1918 and 1931 respectively, for their work in overcoming the chemical and engineering problems posed by the use of large-scale high-pressure technology. Ammonia was first manufactured using the Haber process on an industrial scale in Germany during World War I to meet the high demand for ammonium nitrate (for use in explosives) at a time when supply of Chile saltpetre from Chile could not be guaranteed because this industry was then almost 100% in British hands. It has been suggested that without this process, Germany would almost certainly have run out of explosives by 1916, thereby ending the war. # The process The bulk of the chemical technology consists in getting the hydrogen from methane or natural gas using heterogeneous catalysis and then reacting it with the atmospheric nitrogen. ## Synthesis gas preparation First, the methane is cleaned, mainly to remove sulfur impurities that would poison the catalysts. This is done by turning sulfur into hydrogen sulfide: and then reacting with zinc oxide to form zinc sulfide: The clean methane is then reacted with steam over a catalyst of nickel oxide. This is called steam reforming: Secondary reforming then takes place with the addition of air to convert the methane that did not react during steam reforming. The carbon monoxide formed is also cause catalyst poisoning, which would react with the iron catalyst, forming an iron compound, thus affecting the reaction.[citation needed] The air added during this step also serves as a nitrogen source for ammonia synthesis: Then occur two’’shifts’’ which convert CO to CO2 by reaction with steam, one at high temperature, then one at low temperature: Then the carbon dioxide is removed by reaction with potassium carbonate. The gas mixture is now passed into a methanator which converts any remaining CO2 into methane for recycling: We now have a gas mixture containing nitrogen and hydrogen in the correct ratio of 1:3. ## Ammonia synthesis The final stage is the crucial synthesis of ammonia using promoted magnetite, iron oxide, as the catalyst: This is done at 150 - 250 atmospheres (atm) and between 300 and 550 °C, passing the gases over four beds of catalyst, with cooling between each pass to maintain a reasonable equilibrium constant. On each pass only about 15% conversion occurs, but any unreacted gases will be recycled, so that eventually an overall yield of 98% can be achieved. # Reaction Rate and Equilibrium There are two opposing considerations in this synthesis: the position of the equilibrium and the rate of reaction. At room temperature, the reaction is slow and the obvious solution is to raise the temperature. This may increase the rate of the reaction but, since the reaction is exothermic, it also has the effect, according to Le Chatelier's Principle, of favouring the reverse reaction and thus reducing equilibrium constant, given by: <math>K_\mathrm{eq} = \mathrm{\frac{[NH_3]^2}{[N_2][H_2]^3}}</math> As the temperature increases, the equilibrium is shifted and hence, the constant drops dramatically according to the van't Hoff equation. Thus one might suppose that a low temperature is to be used and some other means to increase rate. However, the catalyst itself requires a temperature of at least 400 °C to be efficient. Pressure is the obvious choice to favour the forward reaction because there are 4 moles of reactant for every 2 moles of product, and the pressure used (around 200 atm) alters the equilibrium concentrations to give a profitable yield. Economically, though, pressure is an expensive commodity. Pipes and reaction vessels need to be strengthened, valves more rigorous, and there are safety considerations of working at 200 atm. In addition, running pumps and compressors takes considerable energy. Thus the compromise used gives a single pass yield of around 15%. Another way to increase the yield of the reaction would be to remove the product (i.e. ammonia gas) from the system. In practice, gaseous ammonia is not removed from the reactor itself, since the temperature is too high; but it is removed from the equilibrium mixture of gases leaving the reaction vessel. The hot gases are cooled enough, whilst maintaining a high pressure, for the ammonia to condense and be removed as liquid. Unreacted hydrogen and nitrogen gases are then returned to the reaction vessel to undergo further reaction. # Catalysts The catalyst has no effect on the position of equilibrium, rather, it provides an alternative pathway with lower activation energy and hence increases the reaction rate, while remaining chemically unchanged at the end of the reaction. The first Haber–Bosch reaction chambers used osmium and uranium catalysts. However, today a much less expensive iron catalyst is used almost exclusively. In industrial practice, the iron catalyst is prepared by exposing a mass of magnetite, an iron oxide, to the hot hydrogen feedstock. This reduces some of the magnetite to metallic iron, removing oxygen in the process. However, the catalyst maintains most of its bulk volume during the reduction, and so the result is a highly porous material whose large surface area aids its effectiveness as a catalyst. Other minor components of the catalyst include calcium and aluminium oxides, which support the porous iron catalyst and help it maintain its surface area over time, and potassium, which increases the electron density of the catalyst and so improves its reactivity. The reaction mechanism, involving the heterogeneous catalyst, is believed to be as follows: - N2(g) → N2(adsorbed) - N2(adsorbed) → 2N(adsorbed) - H2(g) → H2(adsorbed) - H2(adsorbed) → 2H(adsorbed) - N(adsorbed) + 3H(adsorbed)→ NH3(adsorbed) - NH3(adsorbed) → NH3(g) Reaction 5 occurs in three steps, forming NH, NH2, and then NH3. Experimental evidence points to reaction 2 as being the slow, rate-determining step. A major contributor to the elucidation of this mechanism is Gerhard Ertl.[5][6][7][8] # Economic and environmental aspects The Haber process now produces 100 million tons of nitrogen fertilizer per year, mostly in the form of anhydrous ammonia, ammonium nitrate, and urea. 3-5% of world natural gas production is consumed in the Haber process (~1-2% of the world's annual energy supply)[1],[9],[10],[11]. That fertilizer is responsible for sustaining one-third of the Earth's population, as well as various deleterious environmental consequences.[12] Generation of hydrogen using electrolysis of water, using renewable energy, is not currently competitive cost-wise with hydrogen from fossil fuels, such as natural gas, and is responsible for only 4% of current hydrogen production. Notably, the rise of this industrial process led to the "Nitrate Crisis" in Chile, when the British industrials left the country -- since the natural nitrate mines were no longer profitable -- closing the mines and leaving a large unemployed Chilean population behind.	https://www.wikidoc.org/index.php/Haber-Bosch
f139b056f0dec20ce9283a45b3664d12efe084dd	wikidoc	Hemagglutinin	Hemagglutinin Hemagglutinin (HA) or haemagglutinin (BE) is an antigenic glycoprotein found on the surface of the influenza viruses (as well as many other bacteria and viruses). It is responsible for binding the virus to the cell that is being infected. The name "hemagglutinin" comes from the protein's ability to cause red blood cells (erythrocytes) to clump together ("agglutinate") in vitro . # Subtypes There are at least 16 different HA antigens. These subtypes are labeled H1 through H16. The last, H16, was discovered only recently on influenza A viruses isolated from black-headed gulls from Sweden and Norway. The first three hemagglutinins, H1, H2, and H3, are found in human influenza viruses. A highly pathogenic avian flu virus of H5N1 type has been found to infect humans at a low rate. It has been reported that single amino acid changes in this avian virus strain's type H5 hemagglutinin have been found in human patients that "can significantly alter receptor specificity of avian H5N1 viruses, providing them with an ability to bind to receptors optimal for human influenza viruses". This finding seems to explain how an H5N1 virus that normally does not infect humans can mutate and become able to efficiently infect human cells. The hemagglutinin of the H5N1 virus has been associated with the high pathogenicity of this flu virus strain, apparently due to its ease of conversion to an active form by proteolysis (Senne 1996, Hatta 2001). # Functions and mechanisms of action HA has two primary functions: - allowing the recognition of target vertebrate cells, accomplished through the binding of these cells' sialic acid-containing receptors, and - allowing the entry of the viral genome into the target cells by causing the fusion of host endosomal membrane with the viral membrane (White 1997), Mechanism: HA binds to an as yet unidentified glycoprotein which is present on the surface of its target cells. This causes the viral particles to stick to the cell's surface. The cell membrane then engulfs the virus and the portion of the membrane that encloses it pinches off to form a new membrane-bound compartment within the cell called an endosome, which contains the engulfed virus. The cell then attempts to begin digesting the contents of the endosome by acidifying its interior and transforming it into a lysosome. However, as soon as the pH within the endosome drops to about 6.0, the original folded structure of the HA molecule becomes unstable, causing it to partially unfold, and releasing a very hydrophobic portion of its peptide chain that was previously hidden within the protein. This so-called "fusion peptide" acts like a molecular grappling hook by inserting itself into the endosomal membrane and locking on. Then, when the rest of the HA molecule refolds into a new structure (which is more stable at the lower pH), it "retracts the grappling hook" and pulls the endosomal membrane right up next to the virus particle's own membrane, causing the two to fuse together. Once this has happened, the contents of the virus, including its RNA genome, are free to pour out into the cell's cytoplasm. (see PDB molecule of the month: Hemagglutinin (April 2006)) # Structure HA is a homotrimeric integral membrane glycoprotein. It is shaped like a cylinder, and is approximately 135 Å (angstroms) long. The three identical monomers that constitute HA are constructed into a central α helix coil; three spherical heads contain the sialic acid binding sites. HA monomers are synthesized as precursors that are then glycosylated and cleaved into two smaller polypeptides: the HA1 and HA2 subunits. Each HA monomer consists of a long, helical chain anchored in the membrane by HA2 and topped by a large HA1 globule. # Sources and notes - ↑ Nelson DL and Cox MM, 2005. Lehninger's Principles of Biochemistry, 4th edition, WH Freeman, New York, NY. - ↑ Fouchier RAM, Munster V, Wallensten A, et al, 2005. Characterization of a novel influenza A virus hemagglutinin subtype (H16) obtained from black-headed gulls. J Virol vol 79, issue 5, pp2814-22 - ↑ Suzuki, Y, 2005. Sialobiology of Influenza: Molecular Mechanism of Host Range Variation of Influenza Viruses in Biological and Pharmaceutical Bulletin, vol 28, pp399-408 - ↑ Gambaryan A, Tuzikov A, Pazynina G, Bovin N, Balish A, Klimov A, 2006. Evolution of the receptor binding phenotype of influenza A (H5) viruses in Virology vol 344, issue 2, pp432-8 - Yamada S, Suzuki Y, Suzuki T, et al, 2006 Haemagglutinin mutations responsible for the binding of H5N1 influenza A viruses to human-type receptors. Nature vol 444, issue 7117, pp378-82. - Hatta M, Gao P, Halfmann P, Kawaoka Y, 2001. Molecular Basis for High Virulence of Hong Kong H5N1 Influenza A Viruses in Science vol 293, pp1840-1842. - Senne DA, Panigrahy B, Kawaoka Y, Pearson JE, Suss J, Lipkind M, Kida H, Webster RG, 1996. Survey of the hemagglutinin (HA) cleavage site sequence of H5 and H7 avian influenza viruses: amino acid sequence at the HA cleavage site as a marker of pathogenicity potential in Avian Disease vol 40, pp425-437. - Weis WI, Brünger AT, Skehel JJ, et al, 1990. Refinement of the influenza virus hemagglutinin by simulated annealing. J Mol Biol vol 212, pp737-761. - White JM, Hoffman LR, Arevalo JH, et al, 1997. Attachment and entry of influenza virus into host cells. Pivotal roles of hemagglutinin. In Structural Biology of Viruses. Chiu W, Burnett RM, and Garcea RL, editors. Oxford University Press, NY. pp80-104.	Hemagglutinin Hemagglutinin (HA) or haemagglutinin (BE) is an antigenic glycoprotein found on the surface of the influenza viruses (as well as many other bacteria and viruses). It is responsible for binding the virus to the cell that is being infected. The name "hemagglutinin" comes from the protein's ability to cause red blood cells (erythrocytes) to clump together ("agglutinate") in vitro [1]. # Subtypes There are at least 16 different HA antigens. These subtypes are labeled H1 through H16. The last, H16, was discovered only recently on influenza A viruses isolated from black-headed gulls from Sweden and Norway[2]. The first three hemagglutinins, H1, H2, and H3, are found in human influenza viruses. A highly pathogenic avian flu virus of H5N1 type has been found to infect humans at a low rate. It has been reported that single amino acid changes in this avian virus strain's type H5 hemagglutinin have been found in human patients that "can significantly alter receptor specificity of avian H5N1 viruses, providing them with an ability to bind to receptors optimal for human influenza viruses"[3][4]. This finding seems to explain how an H5N1 virus that normally does not infect humans can mutate and become able to efficiently infect human cells. The hemagglutinin of the H5N1 virus has been associated with the high pathogenicity of this flu virus strain, apparently due to its ease of conversion to an active form by proteolysis (Senne 1996, Hatta 2001). # Functions and mechanisms of action HA has two primary functions: - allowing the recognition of target vertebrate cells, accomplished through the binding of these cells' sialic acid-containing receptors, and - allowing the entry of the viral genome into the target cells by causing the fusion of host endosomal membrane with the viral membrane (White 1997), Mechanism: HA binds to an as yet unidentified glycoprotein which is present on the surface of its target cells. This causes the viral particles to stick to the cell's surface. The cell membrane then engulfs the virus and the portion of the membrane that encloses it pinches off to form a new membrane-bound compartment within the cell called an endosome, which contains the engulfed virus. The cell then attempts to begin digesting the contents of the endosome by acidifying its interior and transforming it into a lysosome. However, as soon as the pH within the endosome drops to about 6.0, the original folded structure of the HA molecule becomes unstable, causing it to partially unfold, and releasing a very hydrophobic portion of its peptide chain that was previously hidden within the protein. This so-called "fusion peptide" acts like a molecular grappling hook by inserting itself into the endosomal membrane and locking on. Then, when the rest of the HA molecule refolds into a new structure (which is more stable at the lower pH), it "retracts the grappling hook" and pulls the endosomal membrane right up next to the virus particle's own membrane, causing the two to fuse together. Once this has happened, the contents of the virus, including its RNA genome, are free to pour out into the cell's cytoplasm. (see PDB molecule of the month: Hemagglutinin (April 2006)) # Structure HA is a homotrimeric integral membrane glycoprotein. It is shaped like a cylinder, and is approximately 135 Å (angstroms) long. The three identical monomers that constitute HA are constructed into a central α helix coil; three spherical heads contain the sialic acid binding sites. HA monomers are synthesized as precursors that are then glycosylated and cleaved into two smaller polypeptides: the HA1 and HA2 subunits. Each HA monomer consists of a long, helical chain anchored in the membrane by HA2 and topped by a large HA1 globule. # Sources and notes - ↑ Nelson DL and Cox MM, 2005. Lehninger's Principles of Biochemistry, 4th edition, WH Freeman, New York, NY. - ↑ Fouchier RAM, Munster V, Wallensten A, et al, 2005. Characterization of a novel influenza A virus hemagglutinin subtype (H16) obtained from black-headed gulls. J Virol vol 79, issue 5, pp2814-22 - ↑ Suzuki, Y, 2005. Sialobiology of Influenza: Molecular Mechanism of Host Range Variation of Influenza Viruses in Biological and Pharmaceutical Bulletin, vol 28, pp399-408 - ↑ Gambaryan A, Tuzikov A, Pazynina G, Bovin N, Balish A, Klimov A, 2006. Evolution of the receptor binding phenotype of influenza A (H5) viruses in Virology vol 344, issue 2, pp432-8 - Yamada S, Suzuki Y, Suzuki T, et al, 2006 Haemagglutinin mutations responsible for the binding of H5N1 influenza A viruses to human-type receptors. Nature vol 444, issue 7117, pp378-82. - Hatta M, Gao P, Halfmann P, Kawaoka Y, 2001. Molecular Basis for High Virulence of Hong Kong H5N1 Influenza A Viruses in Science vol 293, pp1840-1842. - Senne DA, Panigrahy B, Kawaoka Y, Pearson JE, Suss J, Lipkind M, Kida H, Webster RG, 1996. Survey of the hemagglutinin (HA) cleavage site sequence of H5 and H7 avian influenza viruses: amino acid sequence at the HA cleavage site as a marker of pathogenicity potential in Avian Disease vol 40, pp425-437. - Weis WI, Brünger AT, Skehel JJ, et al, 1990. Refinement of the influenza virus hemagglutinin by simulated annealing. J Mol Biol vol 212, pp737-761. - White JM, Hoffman LR, Arevalo JH, et al, 1997. Attachment and entry of influenza virus into host cells. Pivotal roles of hemagglutinin. In Structural Biology of Viruses. Chiu W, Burnett RM, and Garcea RL, editors. Oxford University Press, NY. pp80-104.	https://www.wikidoc.org/index.php/Haemagglutinin
b2f7f3755c5eae6820b1aa41e403ed2878407dbd	wikidoc	Hand strength	Hand strength Hand strength measurements are of interest to study pathology of the hand that involves loss of muscle strength. Examples of these pathologies are carpal tunnel syndrome, nerve injury, tendon injuries of the hand, and neuromuscular disorders. Hand strength testing is frequently used for clinical decision-making and outcome evaluation in evidence based medicine. It is used to diagnose diseases, to evaluate and compare treatments, to document progression of muscle strength, and to provide feedback during the rehabilitation process. In addition, strength testing is often used in areas such as sports medicine and ergonomics. In general, hand strength measurements can be divided into manual muscle testing and dynamometry. # Manual muscle strength testing of the hand muscles In clinical practice, hand muscles are most often evaluated using manual muscle strength testing using the Medical Research Council (MRC) Scale. In this scale, muscle strength is graded on a scale from 0 to 5. For evaluating the strength of the intrinsic hand muscles, a small modification to the standard MRC grading has been made so that grade 3 indicates ‘full active range of motion’ as compared to ‘movement against gravity’: ## Modified Medical Research Council Scale for measuring hand muscles Grade 5: full active range of motion & Normal muscle resistance Grade 4: full active range of motion & Reduced muscle resistance Grade 3: full active range of motion & No muscle resistance Grade 2: Reduced active range of motion & No muscle resistance Grade 1: No active range of motion & Palpable muscle contraction only Grade 0: No active range of motion & No palpable muscle contraction Manual muscle testing, however, has a number of limitations. One limitation is that the MRC scale is an ordinal scale with disproportional distances between grades. Another limitation of the MRC scale is that the scoring depends on the judgment of the examiner. Finally, with the 6-point ordinal MRC scale, it is difficult to identify relatively small but clinically relevant changes in muscle strength. # Grip and pinch dynamometry To create more quantitative assessments of hand muscle strength, dynamometers have been developed. These dynamometer measurements are more sensitive to change compared to manual muscle testing and render outcome on a continuous scale. In clinical evaluation and research studies on patients with hand problems, muscle strength measurements are usually based on grip strength and pinch strength dynamometry. The most commonly used grip and pinch dynamometers are the Jamar dynamometers and similar devices by other manufacturers. In several patients groups, these measurements have a good reliability and validity. In addition, grip- and pinch strength are functionally relevant to measure the combined action of a large number of intrinsic and extrinsic hand muscles as well as the combined action of a number of different joints. By comparing outcome with normative data, the amount of muscle strength loss can be determined. # Dynamometry of the intrinsic hand muscles For more specific dynamometry of the intrinsic muscles, intrinsic hand dynamometers have been developed. The advantage of these dynamometers is that they to do not measure a large number of muscles in combined action, but can measure single actions such as thumb opposition of index finger abduction. One such dynamometer is the Rotterdam Intrinsic Hand Myometer (RIHM). Reliability and validity of this dynamometer is comparable to grip- and pinch dynamometers.	Hand strength Hand strength measurements are of interest to study pathology of the hand that involves loss of muscle strength. Examples of these pathologies are carpal tunnel syndrome, nerve injury, tendon injuries of the hand, and neuromuscular disorders. Hand strength testing is frequently used for clinical decision-making and outcome evaluation in evidence based medicine. It is used to diagnose diseases, to evaluate and compare treatments, to document progression of muscle strength, and to provide feedback during the rehabilitation process. In addition, strength testing is often used in areas such as sports medicine and ergonomics. In general, hand strength measurements can be divided into manual muscle testing and dynamometry. # Manual muscle strength testing of the hand muscles In clinical practice, hand muscles are most often evaluated using manual muscle strength testing using the Medical Research Council (MRC) Scale[1]. In this scale, muscle strength is graded on a scale from 0 to 5. For evaluating the strength of the intrinsic hand muscles, a small modification to the standard MRC grading has been made so that grade 3 indicates ‘full active range of motion’ as compared to ‘movement against gravity’[2]: ## Modified Medical Research Council Scale for measuring hand muscles Grade 5: full active range of motion & Normal muscle resistance Grade 4: full active range of motion & Reduced muscle resistance Grade 3: full active range of motion & No muscle resistance Grade 2: Reduced active range of motion & No muscle resistance Grade 1: No active range of motion & Palpable muscle contraction only Grade 0: No active range of motion & No palpable muscle contraction Manual muscle testing, however, has a number of limitations. One limitation is that the MRC scale is an ordinal scale with disproportional distances between grades. Another limitation of the MRC scale is that the scoring depends on the judgment of the examiner. Finally, with the 6-point ordinal MRC scale, it is difficult to identify relatively small but clinically relevant changes in muscle strength. # Grip and pinch dynamometry To create more quantitative assessments of hand muscle strength, dynamometers have been developed. These dynamometer measurements are more sensitive to change compared to manual muscle testing and render outcome on a continuous scale. In clinical evaluation and research studies on patients with hand problems, muscle strength measurements are usually based on grip strength and pinch strength dynamometry. The most commonly used grip and pinch dynamometers are the Jamar dynamometers and similar devices by other manufacturers. In several patients groups, these measurements have a good reliability and validity. In addition, grip- and pinch strength are functionally relevant to measure the combined action of a large number of intrinsic and extrinsic hand muscles as well as the combined action of a number of different joints. By comparing outcome with normative data[3], the amount of muscle strength loss can be determined. # Dynamometry of the intrinsic hand muscles For more specific dynamometry of the intrinsic muscles, intrinsic hand dynamometers have been developed. The advantage of these dynamometers is that they to do not measure a large number of muscles in combined action, but can measure single actions such as thumb opposition of index finger abduction[4]. One such dynamometer is the Rotterdam Intrinsic Hand Myometer (RIHM)[5]. Reliability and validity of this dynamometer is comparable to grip- and pinch dynamometers[6][7].	https://www.wikidoc.org/index.php/Hand_strength
c72af0d26067a593f87ab40229d1accae110f504	wikidoc	Harley Street	Harley Street Harley Street is a road in the City of Westminster in London. It is noted for its large number of private dentists, surgeons, and doctors. Its name is synonymous with private medical care in the United Kingdom. Since the 19th century the number of doctors, hospitals and medical organisations in and around Harley Street has greatly increased. Records show that there were around 20 doctors in 1860, 80 by 1900 and almost 200 by 1914. When the National Health Service was established in 1948 there were around 1,500. Today, there are more than 3,000 people employed in the hospitals, clinics and medical practices in the Harley Street area. Harley Street is owned by the de Walden family and managed by the de Walden Estate. The Howard de Walden Estate dates from 1715 when Edward Harley, 2nd Earl of Oxford, began the development of Cavendish Square in London, and the streets around it. This land had previously formed part of the Marylebone Estate of the Dukes of Newcastle. It had passed from Margaret Holles, nee Cavendish, daughter of the 2nd Duke of Newcastle, to her daughter Henrietta Cavendish Harley. At the death of Henrietta's husband, Edward Harley, in 1741, this new Harley Estate passed to his only daughter, Margaret Cavendish Harley, who in 1734 had married William Bentinck, 2nd Duke of Portland. It was subsequently known as the Portland, and was handed down to successive Dukes of Portland. In 1879, the 5th Duke of Portland died without issue and his estates were divided between his sisters, (according to the terms of the 4th Duke's will), and his cousin, who succeeded him as the sixth Duke. The Portland Estate eventually passed to the last surviving sister, Lucy Joan Ellis, who was the widow of the 6th Lord Howard de Walden, and has remained in this family since then. The nearest tube stations are Regent's Park and Oxford Circus.	Harley Street Harley Street is a road in the City of Westminster in London. It is noted for its large number of private dentists, surgeons, and doctors. Its name is synonymous with private medical care in the United Kingdom. Since the 19th century the number of doctors, hospitals and medical organisations in and around Harley Street has greatly increased. Records show that there were around 20 doctors in 1860, 80 by 1900 and almost 200 by 1914. When the National Health Service was established in 1948 there were around 1,500. Today, there are more than 3,000 people employed in the hospitals, clinics and medical practices in the Harley Street area. Harley Street is owned by the de Walden family and managed by the de Walden Estate. The Howard de Walden Estate dates from 1715 when Edward Harley, 2nd Earl of Oxford, began the development of Cavendish Square in London, and the streets around it. This land had previously formed part of the Marylebone Estate of the Dukes of Newcastle. It had passed from Margaret Holles, nee Cavendish, daughter of the 2nd Duke of Newcastle, to her daughter Henrietta Cavendish Harley. At the death of Henrietta's husband, Edward Harley, in 1741, this new Harley Estate passed to his only daughter, Margaret Cavendish Harley, who in 1734 had married William Bentinck, 2nd Duke of Portland. It was subsequently known as the Portland, and was handed down to successive Dukes of Portland. In 1879, the 5th Duke of Portland died without issue and his estates were divided between his sisters, (according to the terms of the 4th Duke's will), and his cousin, who succeeded him as the sixth Duke. The Portland Estate eventually passed to the last surviving sister, Lucy Joan Ellis, who was the widow of the 6th Lord Howard de Walden, and has remained in this family since then. [1] The nearest tube stations are Regent's Park and Oxford Circus.	https://www.wikidoc.org/index.php/Harley_Street
cf7f0251f655b85d47b564ce85f886275ef19516	wikidoc	Harpagophytum	Harpagophytum Harpagophytum procumbens, also called grapple plant, wood spider and most commonly Devil's Claw, is a plant of the sesame family, native to South Africa. It got its name from the peculiar appearance of its hooked fruit. The plant's large tuberous roots are used medicinally to reduce pain and fever, and to stimulate digestion. European colonists brought Devil's Claw home where it was used to treat arthritis. H. procumbens are mainly found in the eastern and south eastern parts of Namibia, Southern Botswana and the Kalahari region of the Northern Cape, South Africa. H. Zeyheri is found in the northern parts of Namibia (Ovamboland) and southern Angola. The active ingredient is harpagoside with values ranging in both species from 1.0% to 3.3%. The name "devil's claw" is also used for several species of North American plants in the genus Proboscidea, as well as urtica dioica. # Medicinal Uses The two active ingredients in Devil's Claw are Harpagoside and Beta sitosterol. It is claimed that these possess anti-inflammatory properties. The British Herbal Pharmacopoeia recognises Devil's Claw as having analgesic, sedative and diuretic properties. Most studies involve chronic use rather than acute treatment of pain. Devil's Claw is also claimed to be beneficial for treating diseases of the liver, kidneys, gallbladder and bladder, arthritis and rheumatism. It is said to help alleviate problems with and improve the vitality of the joints, as well as stimulating appetite and aid digestion, increase cholesterol and fatty acids in the blood. Devil's Claw has been recommended for treating diabetes, hardening of the arteries, lumbago, gastrointestinal disturbances, menstrual difficulties, neuralgia, headache, heartburn and gout. Several studies have been performed using Doloteffin, a standardized preparation of Devil's Claw. A series of small-scale studies completed in Germany found that H. procumbens was indistinguishable from Vioxx in the treatment of chronic low back pain, and was well-tolerated after more than four years of treatment of H. procumbens alone. H. procumbens also seems efficacious in the treatment of arthritis-caused hip and knee pain. An author involved in several studies on Devil's Claw and pain relief had the general conclusion that a minimum 50 mg per dose standardized extract was an alternative to synthetic analgesics with a low risk of adverse events. A separate 2006 systematic review of herbal medications for low back pain reached the conclusion that a standardized daily dose between 50 and 100 mg of harpagoside performed better than a placebo, and an unspecified dose of harpagoside demonstrated relative equivalence to 12.5 mg per day of Vioxx. Devil's claw can also be used externally to treat sores, ulcers, boils and skin lesions. # Adverse reactions Devil's claw may interfere with the action of Ticlopidine and Warfarin, and patients should consult with a physician before combining Devil's claw with these medications. In addition, Devil's Claw promotes the secretion of stomach acid, leading to difficulties in those with peptic ulcers, gastritis or excess stomach acid. Care should also be taken for individuals with gallstones. # Notes - ↑ Applied health article on Devil's Claw - ↑ Due to the natural variability of herbal extracts, the results of studies using different products and preparations are difficult to compare - ↑ Article comparing Vioxx and Doloteffin - ↑ Follow-up study of patients taking Doloteffin alone - ↑ German article on H. procumbens and hip/knee arthritis pain - ↑ German article discussing Devil's Claw extract for pain relief - ↑ Herbal medicine for low back pain (article from NIH) - ↑ Kroger article on Devil's Claw drug interactions - ↑ Kroger article on Devil's Claw	Harpagophytum Harpagophytum procumbens, also called grapple plant, wood spider and most commonly Devil's Claw, is a plant of the sesame family, native to South Africa. It got its name from the peculiar appearance of its hooked fruit. The plant's large tuberous roots are used medicinally to reduce pain and fever, and to stimulate digestion. European colonists brought Devil's Claw home where it was used to treat arthritis. H. procumbens are mainly found in the eastern and south eastern parts of Namibia, Southern Botswana and the Kalahari region of the Northern Cape, South Africa. H. Zeyheri is found in the northern parts of Namibia (Ovamboland) and southern Angola. The active ingredient is harpagoside with values ranging in both species from 1.0% to 3.3%. The name "devil's claw" is also used for several species of North American plants in the genus Proboscidea, as well as urtica dioica. # Medicinal Uses The two active ingredients in Devil's Claw are Harpagoside and Beta sitosterol. It is claimed that these possess anti-inflammatory properties. The British Herbal Pharmacopoeia recognises Devil's Claw as having analgesic, sedative and diuretic properties. Most studies involve chronic use rather than acute treatment of pain. Devil's Claw is also claimed to be beneficial for treating diseases of the liver, kidneys, gallbladder and bladder, arthritis and rheumatism. It is said to help alleviate problems with and improve the vitality of the joints, as well as stimulating appetite and aid digestion, increase cholesterol and fatty acids in the blood. Devil's Claw has been recommended for treating diabetes, hardening of the arteries, lumbago, gastrointestinal disturbances, menstrual difficulties, neuralgia, headache, heartburn and gout.[1] Several studies have been performed using Doloteffin, a standardized preparation of Devil's Claw.[2] A series of small-scale studies completed in Germany found that H. procumbens was indistinguishable from Vioxx in the treatment of chronic low back pain,[3] and was well-tolerated after more than four years of treatment of H. procumbens alone.[4] H. procumbens also seems efficacious in the treatment of arthritis-caused hip and knee pain.[5] An author involved in several studies on Devil's Claw and pain relief had the general conclusion that a minimum 50 mg per dose standardized extract was an alternative to synthetic analgesics with a low risk of adverse events.[6] A separate 2006 systematic review of herbal medications for low back pain reached the conclusion that a standardized daily dose between 50 and 100 mg of harpagoside performed better than a placebo, and an unspecified dose of harpagoside demonstrated relative equivalence to 12.5 mg per day of Vioxx.[7] Devil's claw can also be used externally to treat sores, ulcers, boils and skin lesions. # Adverse reactions Devil's claw may interfere with the action of Ticlopidine and Warfarin, and patients should consult with a physician before combining Devil's claw with these medications.[8] In addition, Devil's Claw promotes the secretion of stomach acid, leading to difficulties in those with peptic ulcers, gastritis or excess stomach acid. Care should also be taken for individuals with gallstones.[9] # Notes - ↑ Applied health article on Devil's Claw - ↑ Due to the natural variability of herbal extracts, the results of studies using different products and preparations are difficult to compare - ↑ Article comparing Vioxx and Doloteffin - ↑ Follow-up study of patients taking Doloteffin alone - ↑ German article on H. procumbens and hip/knee arthritis pain - ↑ German article discussing Devil's Claw extract for pain relief - ↑ Herbal medicine for low back pain (article from NIH) - ↑ Kroger article on Devil's Claw drug interactions - ↑ Kroger article on Devil's Claw	https://www.wikidoc.org/index.php/Harpagophytum
3a89f46beb62fb3b589402405e95c36d97a41e5c	wikidoc	HeartSoundApp	HeartSoundApp $(document).ready(function () { $("#step2").css("visibility", "hidden"); $("#step3").css("visibility", "hidden"); $("#open").click(function () { if ($("#fileLocation").val().length > 0) { $("#imageHolder").html(""); $("#step2").css("visibility", "visible"); $("#step1").css({"visibility":"hidden","height":"0px"}); $("#add").click(function () { if ($("#soundLocation").val().length > 0) { var top = Math.round($("#imageHolder").offset().top) + 200; var left = Math.round($("#imageHolder").offset().left) + 200; var style = "position:absolute; top:" + top.toString() + "px; left:" + left.toString() + "px; width:25px; height:25px; border:1px solid #000;"; $("#imageHolder").append(""); $("#soundLocation").val(""); $("#imageHolder div").last().draggable(); $("#save").click(function () { $("#step3").css("visibility", "visible"); $("#output").val("" + $("#imageHolder").children("img").outerHTML + "\r\n"); $("#imageHolder div").each(function () { var left = Math.round($(this).position().left - $("#imageHolder").position().left); var top = Math.round($(this).position().top - $("#imageHolder").position().top); $("#output").val($("#output").val() + "\r\n"); $("#output").val($("#output").val() + "");	HeartSoundApp $(document).ready(function () { $("#step2").css("visibility", "hidden"); $("#step3").css("visibility", "hidden"); $("#open").click(function () { if ($("#fileLocation").val().length > 0) { $("#imageHolder").html("<img src='" + $("#fileLocation").val() + "' />"); $("#step2").css("visibility", "visible"); $("#step1").css({"visibility":"hidden","height":"0px"}); } }); $("#add").click(function () { if ($("#soundLocation").val().length > 0) { var top = Math.round($("#imageHolder").offset().top) + 200; var left = Math.round($("#imageHolder").offset().left) + 200; var style = "position:absolute; top:" + top.toString() + "px; left:" + left.toString() + "px; width:25px; height:25px; border:1px solid #000;"; $("#imageHolder").append("<div data-src='" + $("#soundLocation").val() + "' style='" + style + "'></div>"); $("#soundLocation").val(""); $("#imageHolder div").last().draggable(); } }); $("#save").click(function () { $("#step3").css("visibility", "visible"); $("#output").val("<div id='imageHolder'>" + $("#imageHolder").children("img")[0].outerHTML + "\r\n"); $("#imageHolder div").each(function () { var left = Math.round($(this).position().left - $("#imageHolder").position().left); var top = Math.round($(this).position().top - $("#imageHolder").position().top); $("#output").val($("#output").val() + "<div data-src='" + $(this).attr("data-src") + "' data-left='" + left + "' data-top='" + top + "' class='soundBox'></div>\r\n"); }); $("#output").val($("#output").val() + "</div>"); }); });	https://www.wikidoc.org/index.php/HeartSoundApp
e360a2ffdaba8d78d847ae1ab0f0b5c2b13c88cb	wikidoc	Heart chamber	Heart chamber Heart chamber is a general term used to refer to any of the four chambers of the mammalian heart (an organ): - Right atrium: receives oxygen-depleted blood from the body via the superior vena cava and the inferior vena cava and pumps it through the tricuspid valve into the right ventricle. - Right ventricle: receives oxygen-depleted blood from the right atrium and pumps it through the pulmonary valve into the lungs via the pulmonary artery. - Left atrium: receives oxygen-rich blood from the lungs via the pulmonary veins and pumps it through the mitral valve into the left ventricle. - Left ventricle: receives oxygen-rich blood from the left atrium and pumps it through the aortic valve to be delivered throughout the body, including to the heart muscle itself via the coronary arteries.	Heart chamber Template:WikiDoc Cardiology News Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Heart chamber is a general term used to refer to any of the four chambers of the mammalian heart (an organ): - Right atrium: receives oxygen-depleted blood from the body via the superior vena cava and the inferior vena cava and pumps it through the tricuspid valve into the right ventricle. - Right ventricle: receives oxygen-depleted blood from the right atrium and pumps it through the pulmonary valve into the lungs via the pulmonary artery. - Left atrium: receives oxygen-rich blood from the lungs via the pulmonary veins and pumps it through the mitral valve into the left ventricle. - Left ventricle: receives oxygen-rich blood from the left atrium and pumps it through the aortic valve to be delivered throughout the body, including to the heart muscle itself via the coronary arteries. Template:WikiDoc Sources	https://www.wikidoc.org/index.php/Heart_chamber
5dbe952ba732532e18abe303e690217b9d504fa9	wikidoc	Heat transfer	Heat transfer # Overview In thermal physics, heat transfer is the passage of thermal energy from a hot to a colder body. When a physical body, e.g. an object or fluid, is at a different temperature than its surroundings or another body, transfer of thermal energy, also known as heat transfer, or heat exchange, occurs in such a way that the body and the surroundings reach thermal equilibrium. Heat transfer always occurs from a hot body to a cold one, a result of the second law of thermodynamics. Where there is a temperature difference between objects in proximity, heat transfer between them can never be stopped; it can only be slowed down. # Overview Classical transfer of thermal energy occurs only through conduction, convection, radiation or any combination of these. Heat transfer associated with carriage of the heat of phase change by a substance (such as steam which carries the heat of boiling) can be fundamentally treated as a variation of convection heat transfer. In each case, the driving force for heat transfer is a difference of temperature.There are 3 types of heat transfer known as convection, conduction and radiation. Heat transfer is of particular interest to engineers, who attempt to understand and control the flow of heat through the use of thermal insulation, heat exchangers, and other devices. Heat transfer is typically taught as undergraduate and graduate subjects in chemical, electrical and mechanical engineering curricula. - Heat — a transfer of thermal energy, (i.e., of energy and entropy) from hotter material to cooler material. Heat transfer may change the internal energy of materials. - Internal energy — the internal vibrational energy that the molecules or electrons composing all materials contain (except at absolute zero) - Conduction — transfer of heat by electron diffusion or phonon vibrations (see below) - Convection — transfer of heat by conduction in a moving medium, such as a fluid (see below) - Radiation — transfer of heat by electromagnetic radiation or, equivalently, by photons (see below). - Phase change — transfer of heat by the potential energy associated with the heat of phase change, such as boiling, condensation, or freezing. - 1-D Application Using Thermal Circuits — application of heat transfer analysis using the concept of thermal circuits. # Conduction Conduction is the transfer of thermal energy from a region of higher temperature to a region of lower temperature through direct molecular communication within a medium or between mediums in direct physical contact without a flow of the material medium. The transfer of energy could be primarily by elastic impact as in fluids or by free electron diffusion as predominant in metals or phonon vibration as predominant in insulators. In other words, heat is transferred by conduction when adjacent atoms vibrate against one another, or as electrons move from atom to atom. Conduction is greater in solids, where atoms are in constant contact. In liquids (except liquid metals) and gases, the molecules are usually further apart, giving a lower chance of molecules colliding and passing on thermal energy. Heat conduction is directly analogous to diffusion of particles into a fluid, in the situation where there are no fluid currents. This type of heat diffusion differs from mass diffusion in behaviour, only in as much as it can occur in solids, whereas mass diffusion is limited to fluids. Metals (eg. copper) are usually the best conductors of thermal energy. This is due to the way that metals are chemically bonded: metallic bonds (as opposed to covalent or ionic bonds) have free-moving electrons and form a crystalline structure, greatly aiding in the transfer of thermal energy. As density decreases so does conduction. Therefore, fluids (and especially gases) are less conductive. This is due to the large distance between atoms in a gas: fewer collisions between atoms means less conduction. Conductivity of gases increases with temperature but only slightly with pressure near and above atmospheric. Conduction does not occur at all in a perfect vacuum. To quantify the ease with which a particular medium conducts, engineers employ the thermal conductivity, also known as the conductivity constant or conduction coefficient, k. The main article on thermal conductivity defines k as "the quantity of heat, Q, transmitted in time (t) through a thickness (L), in a direction normal to a surface of area (A), due to a temperature difference (ΔT) ." Thermal conductivity is a material property that is primarily dependent on the medium's phase, temperature, density, and molecular bonding. A heat pipe is a passive device that is constructed in such a way that it acts as though it has extremely high thermal conductivity.Note that conduction always takes place from higher to lower temprature. # Convection Convection is a combination of conduction and the transfer of thermal energy by fluid circulation or movement of the hot particles in bulk to cooler areas in a material medium. Unlike the case of pure conduction, now currents in fluids are additionally involved in convection. This movement occurs into a fluid or within a fluid, and cannot happen in solids. In solids, molecules keep their relative position to such an extent that bulk movement or flow is prohibited, and therefore convection does not occur. Convection occurs in two forms: natural and forced convection. In natural convection, fluid surrounding a heat source receives heat, becomes less dense and rises. The surrounding, cooler fluid then moves to replace it. This cooler fluid is then heated and the process continues, forming a convection current. The driving force for natural convection is buoyancy, a result of differences in fluid density when gravity or any type of acceleration is present in the system. Forced convection, by contrast, occurs when pumps, fans or other means are used to propel the fluid and create an artificially induced convection current. Forced heat convection is sometimes referred to as heat advection, or sometimes simply advection for short. But advection is a more general process, and in heat advection, the substance being "advected" in the fluid field is simply heat (rather than mass, which is the other natural component in such situations, as mass transfer and heat transfer share generally the same equations). In some heat transfer systems, both natural and forced convection contribute significantly to the rate of heat transfer. To calculate the rate of convection between an object and the surrounding fluid, engineers employ the heat transfer coefficient, h. Unlike the thermal conductivity, the heat transfer coefficient is not a material property. The heat transfer coefficient depends upon the geometry, fluid, temperature, velocity, and other characteristics of the system in which convection occurs. Therefore, the heat transfer coefficient must be derived or found experimentally for every system analyzed. Formulae and correlations are available in many references to calculate heat transfer coefficients for typical configurations and fluids. # Radiation Radiation is the transfer of heat through electromagnetic radiation. Hot or cold, all objects radiate energy at a rate equal to their emissivity times the rate at which energy would radiate from them if they were a black body. No medium is necessary for radiation to occur; radiation works even in and through a perfect vacuum. The energy from the Sun travels through the vacuum of space before warming the earth. Also, the only way that energy can leave earth is by being radiated to space. Both reflectivity and emissivity of all bodies is wavelength dependent. The temperature determines the wavelength distribution of the electromagnetic radiation as limited in intensity by Planck’s law of black-body radiation. For any body the reflectivity depends on the wavelength distribution of incoming electromagnetic radiation and therefore the temperature of the source of the radiation while the emissivity depends on the wave length distribution and therefore the temperature of the body itself. For example, fresh snow, which is highly reflective to visible light, (reflectivity about 0.90) appears white due to reflecting sunlight with a peak energy wavelength of about 0.5 micrometres. Its emissivity, however, at a temperature of about -5C, peak energy wavelength of about 12 micrometres, is 0.99. Gases absorb and emit energy in characteristic wavelength patterns that are different for each gas. Visible light is simply another form of electromagnetic radiation with a shorter wavelength (and therefore a higher frequency) than infrared radiation. The difference between visible light and the radiation from objects at conventional temperatures is a factor of about 20 in frequency and wavelength; the two kinds of emission are simply different "colors" of electromagnetic radiation. # Newton's law of cooling A related principle, Newton's law of cooling, states that the rate of heat loss of a body is proportional to the difference in temperatures between the body and its surroundings, or environment. The law is This form of heat loss principle is sometimes not very precise; an accurate formulation may require analysis of heat flow, based on the (transient) heat transfer equation in a nonhomogeneous, or else poorly conductive, medium. The following simplification may be applied so long as it is permitted by the Biot number, which relates surface conductance to interior thermal conductivity in a body. If this ratio permits, it shows that the body has relatively high internal conductivity, such that (to good approximation) the entire body is at same uniform temperature as it is cooled from the outside, by the environment. If this is the case, then it is easy to derive from these conditions the behavior of exponential decay of temperature of a body. In such cases, the entire body is treated as lumped capacitance heat reservoir, with total heat content which is proportional to simple total heat capacity, and the temperature of the body. If T(t) is the temperature of such a body at time t, and Tenv is the temperature of the environment around the body, then where The solution of this differential equation, by standard methods of integration and substitution of boundary conditions, gives: Here, T(t) is the temperature at time t, and T(0) is the initial temperature at zero time, or t = 0. If: then the Newtonian solution is written as: Uses: For example, simplified climate models may use Newtonian cooling instead of a full (and computationally expensive) radiation code to maintain atmospheric temperatures.:> heat of vaporisation # One dimensional Application, Using Thermal Circuits A very useful concept used in heat transfer applications is the representation of thermal transfer by what is known as thermal circuits. A thermal circuit is the representation of the resistance to heat flow as though it were an electric resistor. The heat transferred is analogous to the current and the thermal resistance is analogous to the electric resistor. The value of the thermal resistance for the different modes of heat transfer are calculated as the denominators of the developed equations. The thermal resistances of the different modes of heat transfer are used in analyzing combined modes of heat transfer. The equations describing the three heat transfer modes and their thermal resistances, as discussed previously are summarized in the table below: File:Thermal Circuits.jpg In cases where there is heat transfer through different media (for example through a composite), the equivalent resistance is the sum of the resistance of the resistances of the components that make up the composite. Likely, in cases where there are different heat transfer modes, the total resistance is the sum of the resistances of the different modes.Using the thermal circuit concept, the amount of heat transferred through any medium is the quotient of the temperature change and the total thermal resistance of the medium. As an example, consider a composite wall of cross- sectional area A. The composite is made of an L1 long cement plaster with a thermal coefficient k1 and L2 long paper faced fiber glass, with thermal coefficient k2. The left surface of the wall is at Ti and exposed to air with a convective coefficient of hi. The Right surface of the wall is at hi and exposed to air with convective coefficient ho. File:Thermal Circuits2.jpg Image courtesy of Dr. Rong- Yaw Chen, NJIT. Using the thermal resistance concept heat flow through the composite is as follows: File:Thermal Circuits3.jpg # Insulation and radiant barriers Thermal insulators are materials specifically designed to reduce the flow of heat by limiting conduction, convection, or both. Radiant barriers are materials which reflect radiation and therefore reduce the flow of heat from radiation sources. Good insulators are not necessarily good radiant barriers, and vice versa. Metal, for instance, is an excellent reflector and poor insulator. The effectiveness of an insulator is indicated by its R- (resistance) value. The R-value -f a material is the inverse of the conduction coefficient (k) multiplied by the thickness (d) of the insulator. The units of resistance value are in SI units: (K·m²/W) {R} = {d \over k} {C} = {Q \over m \Delta T} Rigid fiberglass, a common insulation material, has an R-value of 4 per inch, while poured concrete, a poor insulator, has an R-value of 0.08 per inch. The effectiveness of a radiant barrier is indicated by its reflectivity, which is the fraction of radiation reflected. A material with a high reflectivity (at a given wavelength) has a low emissivity (at that same wavelength), and vice versa (at any specific wavelength, reflectivity = 1 - emissivity). An ideal radiant barrier would have a reflectivity of 1 and would therefore reflect 100% of incoming radiation. Vacuum bottles (Dewars) are 'silvered' to approach this. In space vacuum, satellites use multi-layer insulation which consists of many layers of aluminized (shiny) mylar to greatly reduce radiation heat transfer and control satellite temperature. # Heat exchangers A Heat exchanger is a device built for efficient heat transfer from one fluid to another, whether the fluids are separated by a solid wall so that they never mix, or the fluids are directly contacted. Heat exchangers are widely used in refrigeration, air conditioning, space heating, power production, and chemical processing. One common example of a heat exchanger is the radiator in a car, in which the hot radiator fluid is cooled by the flow of air over the radiator surface. Common types of heat exchanger flows include parallel flow, counter flow, and cross flow. In parallel flow, both fluids move in the same direction while transferring heat; in counter flow, the fluids move in opposite directions and in cross flow the fluids move at right angles to each other. The common constructions for heat exchanger include shell and tube, double pipe, extruded finned pipe, spiral fin pipe, u-tube, and stacked plate. More information on heat exchanger flows and arrangements can be found in the heat exchanger article. When engineers calculate the theoretical heat transfer in a heat exchanger, they must contend with the fact that the driving temperature difference between the two fluids varies with position. To account for this in simple systems, the log mean temperature difference (LMTD) is often used as an 'average' temperature. In more complex systems, direct knowledge of the LMTD is not available and the number of transfer units (NTU) method can be used instead. # Boiling heat transfer Heat transfer in boiling fluids is complex but of considerable technical importance. It is characterised by an s-shaped curve relating heat flux to surface temperature difference (see say Kay & Nedderman 'Fluid Mechanics & Transfer Processes', CUP, 1985, p529). At low driving temperatures, no boiling occurs and the heat transfer rate is controlled by the usual single-phase mechanisms. As the surface temperature is increased, local boiling occurs and vapour bubbles nucleate, grow into the surrounding cooler fluid, and collapse. This is sub-cooled nucleate boiling and is a very efficient heat transfer mechanism. At high bubble generation rates the bubbles begin to interfere and the heat flux no longer increases rapidly with surface temperature (this is the departure from nucleate boiling DNB). At higher temperatures still, a maximum in the heat flux is reached (the critical heat flux). The regime of falling heat transfer which follows is not easy to study but is believed to be characterised by alternate periods of nucleate and film boiling. Nukleate boiling slowing the heat transfer due to gas phase {bubbles} creation on the heater surfase, as mentioned, gas phase thermal conductivity is much lower than liquid phase thermal conductivity, so the outcome is a kind of "gas thermal barrier". At higher temperatures still, the hydrodynamically quieter regime of film boiling is reached. Heat fluxes across the stable vapour layers are low, but rise slowly with temperature. Any contact between fluid and the surface which may be seen probably leads to the extremely rapid nucleation of a fresh vapour layer ('spontaneous nucleation'). # Condensation heat transfer Condensation occurs when a vapor is cooled and changes its phase to a liquid. Condensation heat transfer, like boiling, is of great significance in industry. During condensation, the latent heat of vaporization must be released. The amount of the heat is the same as that absorbed during vaporization at the same fluid pressure. There are are several modes of condensation: - Homogeneous condensation (as during a formation of fog). - Condensation in direct contact with subcooled liquid. - Condensation on direct contact with a cooling wall of a heat exchanger-this is the most common mode used in industry: Filmwise condensation (when a liquid film is formed on the subcooled surface, usually occurs when the liquid wets the surface). Dropwise condensation (when liquid drops are formed on the subcooled surface, usually occurs when the liquid does not wet the surface). Dropwise condensation is difficult to sustain reliably; therefore, industrial equipment is normally designed to operate in filmwise condensation mode. - Filmwise condensation (when a liquid film is formed on the subcooled surface, usually occurs when the liquid wets the surface). - Dropwise condensation (when liquid drops are formed on the subcooled surface, usually occurs when the liquid does not wet the surface). Dropwise condensation is difficult to sustain reliably; therefore, industrial equipment is normally designed to operate in filmwise condensation mode. # Heat transfer in education Heat transfer is typically studied as part of a general chemical engineering or mechanical engineering curriculum. Typically, thermodynamics is a prerequisite to undertaking a course in heat transfer, as the laws of thermodynamics are essential in understanding the mechanism of heat transfer. Other courses related to heat transfer include energy conversion, thermofluids and mass transfer. Heat transfer methodologies are used in the following disciplines, among others: - Automotive engineering - Thermal management of electronic devices and systems - HVAC - Insulation - Materials processing - Power plant engineering	Heat transfer Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview In thermal physics, heat transfer is the passage of thermal energy from a hot to a colder body. When a physical body, e.g. an object or fluid, is at a different temperature than its surroundings or another body, transfer of thermal energy, also known as heat transfer, or heat exchange, occurs in such a way that the body and the surroundings reach thermal equilibrium. Heat transfer always occurs from a hot body to a cold one, a result of the second law of thermodynamics. Where there is a temperature difference between objects in proximity, heat transfer between them can never be stopped; it can only be slowed down. # Overview Classical transfer of thermal energy occurs only through conduction, convection, radiation or any combination of these. Heat transfer associated with carriage of the heat of phase change by a substance (such as steam which carries the heat of boiling) can be fundamentally treated as a variation of convection heat transfer. In each case, the driving force for heat transfer is a difference of temperature.There are 3 types of heat transfer known as convection, conduction and radiation. Heat transfer is of particular interest to engineers, who attempt to understand and control the flow of heat through the use of thermal insulation, heat exchangers, and other devices. Heat transfer is typically taught as undergraduate and graduate subjects in chemical, electrical and mechanical engineering curricula. - Heat — a transfer of thermal energy, (i.e., of energy and entropy) from hotter material to cooler material. Heat transfer may change the internal energy of materials. - Internal energy — the internal vibrational energy that the molecules or electrons composing all materials contain (except at absolute zero) - Conduction — transfer of heat by electron diffusion or phonon vibrations (see below) - Convection — transfer of heat by conduction in a moving medium, such as a fluid (see below) - Radiation — transfer of heat by electromagnetic radiation or, equivalently, by photons (see below). - Phase change — transfer of heat by the potential energy associated with the heat of phase change, such as boiling, condensation, or freezing. - 1-D Application Using Thermal Circuits — application of heat transfer analysis using the concept of thermal circuits. # Conduction Conduction is the transfer of thermal energy from a region of higher temperature to a region of lower temperature through direct molecular communication within a medium or between mediums in direct physical contact without a flow of the material medium. The transfer of energy could be primarily by elastic impact as in fluids or by free electron diffusion as predominant in metals or phonon vibration as predominant in insulators. In other words, heat is transferred by conduction when adjacent atoms vibrate against one another, or as electrons move from atom to atom. Conduction is greater in solids, where atoms are in constant contact. In liquids (except liquid metals) and gases, the molecules are usually further apart, giving a lower chance of molecules colliding and passing on thermal energy. Heat conduction is directly analogous to diffusion of particles into a fluid, in the situation where there are no fluid currents. This type of heat diffusion differs from mass diffusion in behaviour, only in as much as it can occur in solids, whereas mass diffusion is limited to fluids. Metals (eg. copper) are usually the best conductors of thermal energy. This is due to the way that metals are chemically bonded: metallic bonds (as opposed to covalent or ionic bonds) have free-moving electrons and form a crystalline structure, greatly aiding in the transfer of thermal energy. As density decreases so does conduction. Therefore, fluids (and especially gases) are less conductive. This is due to the large distance between atoms in a gas: fewer collisions between atoms means less conduction. Conductivity of gases increases with temperature but only slightly with pressure near and above atmospheric. Conduction does not occur at all in a perfect vacuum. To quantify the ease with which a particular medium conducts, engineers employ the thermal conductivity, also known as the conductivity constant or conduction coefficient, k. The main article on thermal conductivity defines k as "the quantity of heat, Q, transmitted in time (t) through a thickness (L), in a direction normal to a surface of area (A), due to a temperature difference (ΔT) [...]." Thermal conductivity is a material property that is primarily dependent on the medium's phase, temperature, density, and molecular bonding. A heat pipe is a passive device that is constructed in such a way that it acts as though it has extremely high thermal conductivity.Note that conduction always takes place from higher to lower temprature. # Convection Convection is a combination of conduction and the transfer of thermal energy by fluid circulation or movement of the hot particles in bulk to cooler areas in a material medium. Unlike the case of pure conduction, now currents in fluids are additionally involved in convection. This movement occurs into a fluid or within a fluid, and cannot happen in solids. In solids, molecules keep their relative position to such an extent that bulk movement or flow is prohibited, and therefore convection does not occur. Convection occurs in two forms: natural and forced convection. In natural convection, fluid surrounding a heat source receives heat, becomes less dense and rises. The surrounding, cooler fluid then moves to replace it. This cooler fluid is then heated and the process continues, forming a convection current. The driving force for natural convection is buoyancy, a result of differences in fluid density when gravity or any type of acceleration is present in the system. Forced convection, by contrast, occurs when pumps, fans or other means are used to propel the fluid and create an artificially induced convection current. Forced heat convection is sometimes referred to as heat advection, or sometimes simply advection for short. But advection is a more general process, and in heat advection, the substance being "advected" in the fluid field is simply heat (rather than mass, which is the other natural component in such situations, as mass transfer and heat transfer share generally the same equations). In some heat transfer systems, both natural and forced convection contribute significantly to the rate of heat transfer. To calculate the rate of convection between an object and the surrounding fluid, engineers employ the heat transfer coefficient, h. Unlike the thermal conductivity, the heat transfer coefficient is not a material property. The heat transfer coefficient depends upon the geometry, fluid, temperature, velocity, and other characteristics of the system in which convection occurs. Therefore, the heat transfer coefficient must be derived or found experimentally for every system analyzed. Formulae and correlations are available in many references to calculate heat transfer coefficients for typical configurations and fluids. # Radiation Radiation is the transfer of heat through electromagnetic radiation. Hot or cold, all objects radiate energy at a rate equal to their emissivity times the rate at which energy would radiate from them if they were a black body. No medium is necessary for radiation to occur; radiation works even in and through a perfect vacuum. The energy from the Sun travels through the vacuum of space before warming the earth. Also, the only way that energy can leave earth is by being radiated to space. Both reflectivity and emissivity of all bodies is wavelength dependent. The temperature determines the wavelength distribution of the electromagnetic radiation as limited in intensity by Planck’s law of black-body radiation. For any body the reflectivity depends on the wavelength distribution of incoming electromagnetic radiation and therefore the temperature of the source of the radiation while the emissivity depends on the wave length distribution and therefore the temperature of the body itself. For example, fresh snow, which is highly reflective to visible light, (reflectivity about 0.90) appears white due to reflecting sunlight with a peak energy wavelength of about 0.5 micrometres. Its emissivity, however, at a temperature of about -5C, peak energy wavelength of about 12 micrometres, is 0.99. Gases absorb and emit energy in characteristic wavelength patterns that are different for each gas. Visible light is simply another form of electromagnetic radiation with a shorter wavelength (and therefore a higher frequency) than infrared radiation. The difference between visible light and the radiation from objects at conventional temperatures is a factor of about 20 in frequency and wavelength; the two kinds of emission are simply different "colors" of electromagnetic radiation. # Newton's law of cooling A related principle, Newton's law of cooling, states that the rate of heat loss of a body is proportional to the difference in temperatures between the body and its surroundings, or environment. The law is This form of heat loss principle is sometimes not very precise; an accurate formulation may require analysis of heat flow, based on the (transient) heat transfer equation in a nonhomogeneous, or else poorly conductive, medium. The following simplification may be applied so long as it is permitted by the Biot number, which relates surface conductance to interior thermal conductivity in a body. If this ratio permits, it shows that the body has relatively high internal conductivity, such that (to good approximation) the entire body is at same uniform temperature as it is cooled from the outside, by the environment. If this is the case, then it is easy to derive from these conditions the behavior of exponential decay of temperature of a body. In such cases, the entire body is treated as lumped capacitance heat reservoir, with total heat content which is proportional to simple total heat capacity, and the temperature of the body. If T(t) is the temperature of such a body at time t, and Tenv is the temperature of the environment around the body, then where The solution of this differential equation, by standard methods of integration and substitution of boundary conditions, gives: Here, T(t) is the temperature at time t, and T(0) is the initial temperature at zero time, or t = 0. If: then the Newtonian solution is written as: Uses: For example, simplified climate models may use Newtonian cooling instead of a full (and computationally expensive) radiation code to maintain atmospheric temperatures.:> heat of vaporisation # One dimensional Application, Using Thermal Circuits A very useful concept used in heat transfer applications is the representation of thermal transfer by what is known as thermal circuits. A thermal circuit is the representation of the resistance to heat flow as though it were an electric resistor. The heat transferred is analogous to the current and the thermal resistance is analogous to the electric resistor. The value of the thermal resistance for the different modes of heat transfer are calculated as the denominators of the developed equations. The thermal resistances of the different modes of heat transfer are used in analyzing combined modes of heat transfer. The equations describing the three heat transfer modes and their thermal resistances, as discussed previously are summarized in the table below: File:Thermal Circuits.jpg In cases where there is heat transfer through different media (for example through a composite), the equivalent resistance is the sum of the resistance of the resistances of the components that make up the composite. Likely, in cases where there are different heat transfer modes, the total resistance is the sum of the resistances of the different modes.Using the thermal circuit concept, the amount of heat transferred through any medium is the quotient of the temperature change and the total thermal resistance of the medium. As an example, consider a composite wall of cross- sectional area A. The composite is made of an L1 long cement plaster with a thermal coefficient k1 and L2 long paper faced fiber glass, with thermal coefficient k2. The left surface of the wall is at Ti and exposed to air with a convective coefficient of hi. The Right surface of the wall is at hi and exposed to air with convective coefficient ho. File:Thermal Circuits2.jpg Image courtesy of Dr. Rong- Yaw Chen, NJIT. Using the thermal resistance concept heat flow through the composite is as follows: File:Thermal Circuits3.jpg # Insulation and radiant barriers Thermal insulators are materials specifically designed to reduce the flow of heat by limiting conduction, convection, or both. Radiant barriers are materials which reflect radiation and therefore reduce the flow of heat from radiation sources. Good insulators are not necessarily good radiant barriers, and vice versa. Metal, for instance, is an excellent reflector and poor insulator. The effectiveness of an insulator is indicated by its R- (resistance) value. The R-value of a material is the inverse of the conduction coefficient (k) multiplied by the thickness (d) of the insulator. The units of resistance value are in SI units: (K·m²/W) <math>{R} = {d \over k}</math> <math>{C} = {Q \over m \Delta T}</math> Rigid fiberglass, a common insulation material, has an R-value of 4 per inch, while poured concrete, a poor insulator, has an R-value of 0.08 per inch.[1] The effectiveness of a radiant barrier is indicated by its reflectivity, which is the fraction of radiation reflected. A material with a high reflectivity (at a given wavelength) has a low emissivity (at that same wavelength), and vice versa (at any specific wavelength, reflectivity = 1 - emissivity). An ideal radiant barrier would have a reflectivity of 1 and would therefore reflect 100% of incoming radiation. Vacuum bottles (Dewars) are 'silvered' to approach this. In space vacuum, satellites use multi-layer insulation which consists of many layers of aluminized (shiny) mylar to greatly reduce radiation heat transfer and control satellite temperature. # Heat exchangers A Heat exchanger is a device built for efficient heat transfer from one fluid to another, whether the fluids are separated by a solid wall so that they never mix, or the fluids are directly contacted. Heat exchangers are widely used in refrigeration, air conditioning, space heating, power production, and chemical processing. One common example of a heat exchanger is the radiator in a car, in which the hot radiator fluid is cooled by the flow of air over the radiator surface. Common types of heat exchanger flows include parallel flow, counter flow, and cross flow. In parallel flow, both fluids move in the same direction while transferring heat; in counter flow, the fluids move in opposite directions and in cross flow the fluids move at right angles to each other. The common constructions for heat exchanger include shell and tube, double pipe, extruded finned pipe, spiral fin pipe, u-tube, and stacked plate. More information on heat exchanger flows and arrangements can be found in the heat exchanger article. When engineers calculate the theoretical heat transfer in a heat exchanger, they must contend with the fact that the driving temperature difference between the two fluids varies with position. To account for this in simple systems, the log mean temperature difference (LMTD) is often used as an 'average' temperature. In more complex systems, direct knowledge of the LMTD is not available and the number of transfer units (NTU) method can be used instead. # Boiling heat transfer Heat transfer in boiling fluids is complex but of considerable technical importance. It is characterised by an s-shaped curve relating heat flux to surface temperature difference (see say Kay & Nedderman 'Fluid Mechanics & Transfer Processes', CUP, 1985, p529). At low driving temperatures, no boiling occurs and the heat transfer rate is controlled by the usual single-phase mechanisms. As the surface temperature is increased, local boiling occurs and vapour bubbles nucleate, grow into the surrounding cooler fluid, and collapse. This is sub-cooled nucleate boiling and is a very efficient heat transfer mechanism. At high bubble generation rates the bubbles begin to interfere and the heat flux no longer increases rapidly with surface temperature (this is the departure from nucleate boiling DNB). At higher temperatures still, a maximum in the heat flux is reached (the critical heat flux). The regime of falling heat transfer which follows is not easy to study but is believed to be characterised by alternate periods of nucleate and film boiling. Nukleate boiling slowing the heat transfer due to gas phase {bubbles} creation on the heater surfase, as mentioned, gas phase thermal conductivity is much lower than liquid phase thermal conductivity, so the outcome is a kind of "gas thermal barrier". At higher temperatures still, the hydrodynamically quieter regime of film boiling is reached. Heat fluxes across the stable vapour layers are low, but rise slowly with temperature. Any contact between fluid and the surface which may be seen probably leads to the extremely rapid nucleation of a fresh vapour layer ('spontaneous nucleation'). # Condensation heat transfer Condensation occurs when a vapor is cooled and changes its phase to a liquid. Condensation heat transfer, like boiling, is of great significance in industry. During condensation, the latent heat of vaporization must be released. The amount of the heat is the same as that absorbed during vaporization at the same fluid pressure. There are are several modes of condensation: - Homogeneous condensation (as during a formation of fog). - Condensation in direct contact with subcooled liquid. - Condensation on direct contact with a cooling wall of a heat exchanger-this is the most common mode used in industry: Filmwise condensation (when a liquid film is formed on the subcooled surface, usually occurs when the liquid wets the surface). Dropwise condensation (when liquid drops are formed on the subcooled surface, usually occurs when the liquid does not wet the surface). Dropwise condensation is difficult to sustain reliably; therefore, industrial equipment is normally designed to operate in filmwise condensation mode. - Filmwise condensation (when a liquid film is formed on the subcooled surface, usually occurs when the liquid wets the surface). - Dropwise condensation (when liquid drops are formed on the subcooled surface, usually occurs when the liquid does not wet the surface). Dropwise condensation is difficult to sustain reliably; therefore, industrial equipment is normally designed to operate in filmwise condensation mode. # Heat transfer in education Heat transfer is typically studied as part of a general chemical engineering or mechanical engineering curriculum. Typically, thermodynamics is a prerequisite to undertaking a course in heat transfer, as the laws of thermodynamics are essential in understanding the mechanism of heat transfer. Other courses related to heat transfer include energy conversion, thermofluids and mass transfer. Heat transfer methodologies are used in the following disciplines, among others: - Automotive engineering - Thermal management of electronic devices and systems - HVAC - Insulation - Materials processing - Power plant engineering	https://www.wikidoc.org/index.php/Heat_transfer
8a0978bc01d00222b80ca89f65b1615f4651ed77	wikidoc	Heaven's Gate	Heaven's Gate Heaven's Gate was the name of a religious group led by Marshall Applewhite and Bonnie Nettles. The group's end coincided with the appearance of Comet Hale-Bopp in 1997. Applewhite convinced thirty-eight followers to commit suicide so that their souls could take a ride on a spaceship that they believed was hiding behind the comet carrying Jesus; such beliefs have led some observers to characterize the group as a type of "UFO religion." They believed that the planet Earth was about to be recycled (wiped clean, refurbished and rejuvenated), and that the only chance to survive was to leave it immediately. The group was formally against suicide, but they defined "suicide" to mean "to turn against the Next Level when it is being offered." They were convinced that their "human" bodies were only "vehicles" meant to help them on their journey. The group believed in several paths for a person to leave the Earth and survive before the "recycling", one of which was hating this world strongly enough: "It is also possible that part of our test of faith is our hating this world, even our flesh body, to the extent to be willing to leave it without any proof of the Next Level's existence". # Origins and history Heaven's Gate was founded by Marshall Herff Applewhite and Bonnie Lu Truesdale Nettles sometime before 1975. By the mid-1970s, the two were known within the group as Bo and Peep (respectively), or Do and Ti, or as simply The Two. The Two claimed to have arrived via UFO from another dimension (a "level above human") and would return via a secretive "Process", which was taught to group members. The group never numbered more than a few hundred adherents, and lost many members upon Truesdale Nettles' death in 1985. They were described as a secretive New Age religion. The group held meetings in a hotel on the Oregon coast prior to its move to California. Knowledge of their practices is limited. Upon joining the group, members often sold their possessions in order to break their attachments with earthly existence. For many years the group lived in isolation in the western United States. Members often traveled in pairs and met with other members for meetings or presentations they gave to recruit new members. For a time, group members lived in a darkened house in which they would simulate the experience they expected to have during their long journey in outer space. One of the group's publications, How To Build A U.F.O., purported to describe an interplanetary spacecraft built out of materials such as old tires. Much of what is known about the group comes from the research of Robert Balch and David Taylor, who infiltrated the group in the 1970s. The members of the group added "-ody" to the first names they adopted in lieu of their original given names, which defines "children of the Next Level". This is mentioned in Applewhite's final video, "Do's Final Exit", that was filmed on March 19, 1997, just days prior to the suicides. For a few months prior to their deaths, three members, Thurston-ody, Sylvie-ody, and Elaine-ody, worked for Advanced Development Group (ADG), Inc. (now ManTech Advanced Development Group), a small San Diego-based company that developed computer-based instruction for the U. S. Army. Although they were polite and friendly in a reserved way, they tended to keep to themselves. When they quit working for ADG, they told their supervisor that they had completed their mission. A few weeks later, they were dead. The group also designed Websites, for themselves and for paying clients: one site was for the San Diego Polo Club. One member, Thomas Nichols, was the brother of Star Trek actress Nichelle Nichols. Prior to the group's suicide, he and other members solicited her assistance in publicizing the group's message. The Evan Dando song "Rancho Santa Fe" was reportedly inspired by the group. # Structure The structure of Heaven's Gate resembled that of a medieval monastic order. Group members gave up their material possessions and lived a highly ascetic life devoid of many indulgences. The group was tightly knit and everything was shared communally. Six of the male members of the group voluntarily underwent castration as an extreme means of maintaining the ascetic lifestyle. The group funded itself by offering professional website development for paying clients. # Suicide Thirty-eight group members, plus Applewhite, the group's leader, were found dead in a rented mansion in the upscale San Diego community of Rancho Santa Fe, California, on March 26, 1997. The mass death of the Heaven's Gate group is said to be one of the most widely-known examples of what became publicized as "cult suicide". In preparing to kill themselves, members of the group drank citrus juices to ritually cleanse their bodies of impurities. The suicide was accomplished by ingestion of phenobarbital mixed with vodka, along with plastic bags secured around their heads to induce asphyxiation. They were found lying neatly in their own bunk beds, with their faces and torsos covered by a square, purple cloth. Each member carried five dollar bills and a few quarters in their wallets. All 39 were dressed in identical black shirts and sweat pants, brand new black-and-white Nike tennis shoes, and armband patches reading "Heaven's Gate Away Team". The suicides were conducted in shifts, and the remaining members of the group cleaned up after each prior group's death. # Media coverage prior to suicide Although not widely known to the mainstream media, Heaven's Gate was known in UFOlogical circles; as well as a series of academic studies by Robert Balch, they also received coverage in Jacques Vallee's Messengers of Deception, in which Vallee described an unusual public meeting organized by the group. Vallee frequently expressed concerns within the book about contactee groups' authoritarian political and religious outlooks, and Heaven's Gate did not escape criticism. In January 1994, the LA Weekly ran an article on the group, then known as The Total Overcomers. The article was the reason Rio DiAngelo discovered the group and eventually joined them. Rio was the subject of LA Weekly's 2007 cover story on the group. Louis Theroux contacted the Heaven's Gate group while making a program for his BBC Two documentary series, Louis Theroux's Weird Weekends, in early March 1997. In response to his e-mail, Theroux was told that Heaven's Gate could not take part in the documentary as "at the present time a project like this would be an interference with what we must focus on." # Bibliography - Lalich, Janja. Bounded Choice: True Believers and Charismatic Cults. University of California Press, 2004. ISBN 0-520-23194-5. 329 pp. - Investigative Reports: Inside Heaven's Gate - Balch, Robert W. "Bo and Peep: a case study of the origins of messianic leadership." In Roy Wallis, ed. Millennialism and charisma. Belfast: Queens' University. 1982. - Balch, Robert W. "Waiting for the ships: disillusionment and revitalization of faith in Bo and Peep's UFO cult." In James R. Lewis, ed. The Gods have Landed: New Religions from Other Worlds. Albany: SUNY. 1995. - Balch, Robert W. "When the Light Goes Out, Darkness Comes: A Study of Defection from a Totalistic Cult". in Religious Movements: Genesis, Exodus and Numbers. Rodney Stark, (Ed). Paragon House Publishers. 1985. pp. 11-63. - Theroux, Louis. The Call of the Weird. Pan Macmillian. 2005. pp 207-221 - DiAngelo, Rio. "Beyond Human Mind-The Soul Evolution of Heaven's Gate." RIODIANGELO PRESS. 2007. 128p # Notes - ↑ Hexham, Irving (1997-05-07). "UFO Religion - Making Sense of the Heaven's Gate Suicides". Christian Century. pp. pp.439–440. Retrieved 2007-10-06. Unknown parameter \|coauthors= ignored (help); Check date values in: \|date= (help)CS1 maint: Extra text (link) .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em} - ↑ "Planet About to be Recycled" (HTML). Heaven's Gate Web Site. Retrieved 2007-08-23. - ↑ "Our Position Against Suicide" (HTML). Heaven's Gate Web Site. Retrieved 2007-08-23. - ↑ Grant, John (2006). Discarded Science. Surrey, UK: Artists and Photographers Press, Ltd. pp. 236–237. ISBN 1-904332-49-8. - ↑ "Freaky Oregon Coast Facts: Unusual to Paranormal" (HTML). Beachconnection.net. Retrieved 2007-08-23. - ↑ "Some members of suicide cult castrated". CNN. 1997-03-28. Retrieved 2007-08-23. Check date values in: \|date= (help) - ↑ "First autopsies completed in cult suicide". CNN. 1997-03-28. Retrieved 2007-10-06. Check date values in: \|date= (help) - ↑ Katherine Ramsland. "Death Mansion". All about Heaven's Gate cult. CourtTV Crime Library. Retrieved 2006-09-20. - ↑ Dave Gardetta (1994-01-21). "They Walk Among Us". LA Weekly. Retrieved 2007-08-23. Check date values in: \|date= (help) - ↑ Joshuah Bearman (2007-03-21). "Heaven's Gate: The Sequel". LA Weekly. Check date values in: \|date= (help)	Heaven's Gate Heaven's Gate was the name of a religious group led by Marshall Applewhite and Bonnie Nettles. The group's end coincided with the appearance of Comet Hale-Bopp in 1997. Applewhite convinced thirty-eight followers to commit suicide so that their souls could take a ride on a spaceship that they believed was hiding behind the comet carrying Jesus; such beliefs have led some observers to characterize the group as a type of "UFO religion."[1] They believed that the planet Earth was about to be recycled (wiped clean, refurbished and rejuvenated), and that the only chance to survive was to leave it immediately. [2] The group was formally against suicide, but they defined "suicide" to mean "to turn against the Next Level when it is being offered." [3] They were convinced that their "human" bodies were only "vehicles" meant to help them on their journey. The group believed in several paths for a person to leave the Earth and survive before the "recycling", one of which was hating this world strongly enough: "It is also possible that part of our test of faith is our hating this world, even our flesh body, to the extent to be willing to leave it without any proof of the Next Level's existence". # Origins and history Heaven's Gate was founded by Marshall Herff Applewhite and Bonnie Lu Truesdale Nettles sometime before 1975. By the mid-1970s, the two were known within the group as Bo and Peep (respectively), or Do and Ti, or as simply The Two. The Two claimed to have arrived via UFO from another dimension (a "level above human") and would return via a secretive "Process", which was taught to group members. The group never numbered more than a few hundred adherents, and lost many members upon Truesdale Nettles' death in 1985.[4] They were described as a secretive New Age religion. The group held meetings in a hotel on the Oregon coast prior to its move to California. [5] Knowledge of their practices is limited. Upon joining the group, members often sold their possessions in order to break their attachments with earthly existence. For many years the group lived in isolation in the western United States. Members often traveled in pairs and met with other members for meetings or presentations they gave to recruit new members. For a time, group members lived in a darkened house in which they would simulate the experience they expected to have during their long journey in outer space. One of the group's publications, How To Build A U.F.O., purported to describe an interplanetary spacecraft built out of materials such as old tires. Much of what is known about the group comes from the research of Robert Balch and David Taylor, who infiltrated the group in the 1970s. The members of the group added "-ody" to the first names they adopted in lieu of their original given names, which defines "children of the Next Level". This is mentioned in Applewhite's final video, "Do's Final Exit", that was filmed on March 19, 1997, just days prior to the suicides. For a few months prior to their deaths, three members, Thurston-ody, Sylvie-ody, and Elaine-ody, worked for Advanced Development Group (ADG), Inc. (now ManTech Advanced Development Group), a small San Diego-based company that developed computer-based instruction for the U. S. Army. Although they were polite and friendly in a reserved way, they tended to keep to themselves. When they quit working for ADG, they told their supervisor that they had completed their mission.[citation needed] A few weeks later, they were dead. The group also designed Websites, for themselves and for paying clients: one site was for the San Diego Polo Club. One member, Thomas Nichols, was the brother of Star Trek actress Nichelle Nichols. Prior to the group's suicide, he and other members solicited her assistance in publicizing the group's message. [6] The Evan Dando song "Rancho Santa Fe" was reportedly inspired by the group. # Structure The structure of Heaven's Gate resembled that of a medieval monastic order. Group members gave up their material possessions and lived a highly ascetic life devoid of many indulgences. The group was tightly knit and everything was shared communally. Six of the male members of the group voluntarily underwent castration as an extreme means of maintaining the ascetic lifestyle. The group funded itself by offering professional website development for paying clients. # Suicide Thirty-eight group members, plus Applewhite, the group's leader, were found dead in a rented mansion in the upscale San Diego community of Rancho Santa Fe, California, on March 26, 1997. The mass death of the Heaven's Gate group is said to be one of the most widely-known examples of what became publicized as "cult suicide".[7] In preparing to kill themselves, members of the group drank citrus juices to ritually cleanse their bodies of impurities. The suicide was accomplished by ingestion of phenobarbital mixed with vodka, along with plastic bags secured around their heads to induce asphyxiation. They were found lying neatly in their own bunk beds, with their faces and torsos covered by a square, purple cloth. Each member carried five dollar bills and a few quarters in their wallets. All 39 were dressed in identical black shirts and sweat pants, brand new black-and-white Nike tennis shoes, and armband patches reading "Heaven's Gate Away Team". The suicides were conducted in shifts, and the remaining members of the group cleaned up after each prior group's death.[8] # Media coverage prior to suicide Although not widely known to the mainstream media, Heaven's Gate was known in UFOlogical circles; as well as a series of academic studies by Robert Balch, they also received coverage in Jacques Vallee's Messengers of Deception, in which Vallee described an unusual public meeting organized by the group. Vallee frequently expressed concerns within the book about contactee groups' authoritarian political and religious outlooks, and Heaven's Gate did not escape criticism. In January 1994, the LA Weekly ran an article on the group, then known as The Total Overcomers. The article was the reason Rio DiAngelo discovered the group and eventually joined them. [9] Rio was the subject of LA Weekly's 2007 cover story on the group. [10] Louis Theroux contacted the Heaven's Gate group while making a program for his BBC Two documentary series, Louis Theroux's Weird Weekends, in early March 1997. In response to his e-mail, Theroux was told that Heaven's Gate could not take part in the documentary as "at the present time a project like this would be an interference with what we must focus on."[citation needed] # Bibliography - Lalich, Janja. Bounded Choice: True Believers and Charismatic Cults. University of California Press, 2004. ISBN 0-520-23194-5. 329 pp. - Investigative Reports: Inside Heaven's Gate - Balch, Robert W. "Bo and Peep: a case study of the origins of messianic leadership." In Roy Wallis, ed. Millennialism and charisma. Belfast: Queens' University. 1982. - Balch, Robert W. "Waiting for the ships: disillusionment and revitalization of faith in Bo and Peep's UFO cult." In James R. Lewis, ed. The Gods have Landed: New Religions from Other Worlds. Albany: SUNY. 1995. - Balch, Robert W. "When the Light Goes Out, Darkness Comes: A Study of Defection from a Totalistic Cult". in Religious Movements: Genesis, Exodus and Numbers. Rodney Stark, (Ed). Paragon House Publishers. 1985. pp. 11-63. - Theroux, Louis. The Call of the Weird. Pan Macmillian. 2005. pp 207-221 - DiAngelo, Rio. "Beyond Human Mind-The Soul Evolution of Heaven's Gate." RIODIANGELO PRESS. 2007. 128p # Notes - ↑ Hexham, Irving (1997-05-07). "UFO Religion - Making Sense of the Heaven's Gate Suicides". Christian Century. pp. pp.439–440. Retrieved 2007-10-06. Unknown parameter \|coauthors= ignored (help); Check date values in: \|date= (help)CS1 maint: Extra text (link) .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em} - ↑ "Planet About to be Recycled" (HTML). Heaven's Gate Web Site. Retrieved 2007-08-23. - ↑ "Our Position Against Suicide" (HTML). Heaven's Gate Web Site. Retrieved 2007-08-23. - ↑ Grant, John (2006). Discarded Science. Surrey, UK: Artists and Photographers Press, Ltd. pp. 236–237. ISBN 1-904332-49-8. - ↑ "Freaky Oregon Coast Facts: Unusual to Paranormal" (HTML). Beachconnection.net. Retrieved 2007-08-23. - ↑ "Some members of suicide cult castrated". CNN. 1997-03-28. Retrieved 2007-08-23. Check date values in: \|date= (help) - ↑ "First autopsies completed in cult suicide". CNN. 1997-03-28. Retrieved 2007-10-06. Check date values in: \|date= (help) - ↑ Katherine Ramsland. "Death Mansion". All about Heaven's Gate cult. CourtTV Crime Library. Retrieved 2006-09-20. - ↑ Dave Gardetta (1994-01-21). "They Walk Among Us". LA Weekly. Retrieved 2007-08-23. Check date values in: \|date= (help) - ↑ Joshuah Bearman (2007-03-21). "Heaven's Gate: The Sequel". LA Weekly. Check date values in: \|date= (help) # External links - Official Website (created in Dec 1997) - "How and When HEAVEN'S GATE May Be Entered" (the cult book) - All about Heaven's Gate cult by Katherine Ramsland - The Crime Library - Some members of suicide cult castrated - Heaven's Gate by Jeffrey Hadden of the University of Virginia - TIME magazine Cover Story Out where religion and junk culture meet, some weird new offspring are rising. By Richard Lacayo - L.A. Weekly cover story Heaven's Gate: The Sequel. Ten years after the 39 suicides, the sole survivor is back – and he has something urgent to tell us. By Joshuah Bearman, 3/21/07 - "The Apparent Suicides in Southern California", Talk of the Nation (with host Neal Conan and guests), March 27, 1997] - National Public Radio realaudio stream - Jones, J. Harry (2007-03-18). "Heaven's Gate revisited". San Diego Union-Tribune. Retrieved 2007-03-18. Check date values in: \|date= (help) - Knocking On Heaven's Gate Article by Nigel Watson. - Broder, Jonathan (1997-03-31). "Marshall Applewhite's cry for help". salon.com. Check date values in: \|date= (help) Template:Heavensgate Template:Cult suicide de:Heaven's Gate (Kult) he:שער גן עדן lt:Rojaus vartai simple:Heaven's Gate sh:Nebeska vrata (kult) fi:Heaven's Gate (kultti) sv:Heaven's Gate Template:WikiDoc Sources	https://www.wikidoc.org/index.php/Heaven%27s_Gate
a0aaa76c0f3dfbc6d2037a6b89e055cfdbaccd55	wikidoc	Hedge mustard	Hedge mustard Hedge mustard is a plant, Sisymbrium officinale of the family Cruciferae. It is found on roadsides, wasteland and as a weed of arable land. A native of Europe and North Africa, it is now well-established throughout the world. It is distinct from the Mustard plants which belong to the genus Brassica. The Hedge-mustard is food for the caterpillars of some Lepidoptera, such as the Small White (Pieris rapae). # Relationship with humans The Greeks believed it was an antidote to all poisons. In folk medicine it was used to soothe sore throats - indeed one name for it is singer's plant. Hedge mustard is a diuretic, expectorant, tonic and laxative. herbalists use the juice and flowers to treat bronchitis and stomach ailment, among other uses, and as a revitaliser. This plant is widely cultivated across Europe for its edible leaves and seeds. It is widely used as a condiment in Northern Europe (particularly Denmark, Norway and Germany). The leaves have a bitter cabbage-like flavour and they are used either in salads or cooked as a pot herb (in cultivar versions). The seeds have been used to make mustard pastes in Europe.	Hedge mustard Hedge mustard is a plant, Sisymbrium officinale of the family Cruciferae. It is found on roadsides, wasteland and as a weed of arable land. A native of Europe and North Africa, it is now well-established throughout the world. It is distinct from the Mustard plants which belong to the genus Brassica. The Hedge-mustard is food for the caterpillars of some Lepidoptera, such as the Small White (Pieris rapae). # Relationship with humans The Greeks believed it was an antidote to all poisons. In folk medicine it was used to soothe sore throats - indeed one name for it is singer's plant. Hedge mustard is a diuretic, expectorant, tonic and laxative. herbalists use the juice and flowers to treat bronchitis and stomach ailment, among other uses, and as a revitaliser.[1] This plant is widely cultivated across Europe for its edible leaves and seeds. It is widely used as a condiment in Northern Europe (particularly Denmark, Norway and Germany). The leaves have a bitter cabbage-like flavour and they are used either in salads or cooked as a pot herb (in cultivar versions). The seeds have been used to make mustard pastes in Europe.[2]	https://www.wikidoc.org/index.php/Hedge_mustard
722692e431df9682e9d173f96c262fba44699b68	wikidoc	Helix pomatia	Helix pomatia Helix pomatia, common names the Burgundy snail or Roman snail or edible snail, is a species of large, edible, air-breathing land snail, a terrestrial pulmonate gastropod mollusk in the family Helicidae. It is frequently farmed, and is called by the French name escargot when it is used in cooking. # Distribution This species is native to the limestone areas of central and south-eastern Europe. - Not listed in IUCN red list, not evaluated (NE) - It is mentioned in annex V of Habitats Directive. - Austria - Belgium - The Czech Republic - least concern species (LC). Its Conservation status in 2004-2006 is favourable (FV) in report for European commission in accordance with Habitats Directive. - France - in eastern France - Italy - in northern Italy - Germany. Listed as specially protected species in annex 1 in Bundesartenschutzverordnung. - Netherlands - Russia in the western part - Slovakia - Ukraine - Balkans - Carpathian Mountains - The British Isles, southeastern areas on chalk.	Helix pomatia Helix pomatia, common names the Burgundy snail or Roman snail or edible snail, is a species of large, edible, air-breathing land snail, a terrestrial pulmonate gastropod mollusk in the family Helicidae. It is frequently farmed, and is called by the French name escargot when it is used in cooking. # Distribution This species is native to the limestone areas of central and south-eastern Europe. - Not listed in IUCN red list, not evaluated (NE)[1] - It is mentioned in annex V of Habitats Directive. - Austria - Belgium - The Czech Republic - least concern species (LC). Its Conservation status in 2004-2006 is favourable (FV) in report for European commission in accordance with Habitats Directive.[2] - France - in eastern France - Italy - in northern Italy - Germany. Listed as specially protected species in annex 1 in Bundesartenschutzverordnung. - Netherlands [3] - Russia in the western part - Slovakia - Ukraine - Balkans - Carpathian Mountains - The British Isles, southeastern areas on chalk.	https://www.wikidoc.org/index.php/Helix_pomatia
537df710422bae1a7d65033972132f2a13e3db92	wikidoc	Hematosalpinx	Hematosalpinx Hematosalpinx (sometimes also hemosalpinx) is a medical condition involving bleeding into the fallopian tubes. # Causes A number of causes may account for a hematosalpinx, by far the most common being a tubal pregnancy. Blood may also escape into the peritoneal cavity leading to a hemoperitoneum. A hematosalpinx can also be associated with endometriosis or tubal carcinoma. Further, if menstrual blood flow is obstructed (cryptomenorrhea),caused for instance by a transverse vaginal septum, and gets backed up it may lead to a hematosalpinx. # Symptoms A hematosalpinx from a tubal pregnancy may be associated with pelvic pain and uterine bleeding. A gynecologic ultrasound will show the hematosalpinx. A hematosalpinx from other conditions may be painless but could lead to uterine bleeding. # Treatment Treatment is directed at the underlying condition and usually surgical.	Hematosalpinx Hematosalpinx (sometimes also hemosalpinx) is a medical condition involving bleeding into the fallopian tubes. # Causes A number of causes may account for a hematosalpinx, by far the most common being a tubal pregnancy. Blood may also escape into the peritoneal cavity leading to a hemoperitoneum. A hematosalpinx can also be associated with endometriosis or tubal carcinoma. Further, if menstrual blood flow is obstructed (cryptomenorrhea),caused for instance by a transverse vaginal septum, and gets backed up it may lead to a hematosalpinx. # Symptoms A hematosalpinx from a tubal pregnancy may be associated with pelvic pain and uterine bleeding. A gynecologic ultrasound will show the hematosalpinx. A hematosalpinx from other conditions may be painless but could lead to uterine bleeding. # Treatment Treatment is directed at the underlying condition and usually surgical.	https://www.wikidoc.org/index.php/Hematosalpinx
fded4520274743e1781992b616bce4bd0cd953e3	wikidoc	Hemidesmosome	Hemidesmosome # Overview Hemidesmosomes (HD) are very small stud- or rivet-like structures on the inner basal surface of keratinocytes in the epidermis of skin. They are similar in form to desmosomes. The HD comprises two rivet-like plaques (the inner and outer plaques), together with the anchoring fibrils and anchoring filaments these are collectively termed the HD-stable adhesion complex or HD-anchoring filament complex. Together, the HD-anchoring filament complex forms a continuous structural link between the basal keratinocyte keratin intermediate filaments and the underlying basement membrane zone (BMZ) and dermal components. Over the past decade, these structures have been shown to comprise a variety of some 10 or more molecular components. An example configuration of a hemidesmosome might consist of cytosolic keratin, non-covalently bonded to a cytosolic plectin plaque, which is bonded to a single-pass transmembrane adhesion molecule such as the α6β4 integrin. The integrin might then attach to one of many multi-adhesive proteins such as laminin, resident within the extracellular matrix, thereby forming one of many potential adhesions between cell and matrix. Electron microscopic analysis of the epidermal basement membrane zone (BMZ) reveals that it comprises a narrow and sometimes folded interface between the basal keratinocytes and the dermis. At high power, several complex structures are observed within the epidermal BMZ. The epidermal BMZ shows small (< 0.5 micrometers), regularly spaced electron dense structures which are the hemidesmosomes. Thin, extracellular, electron-dense lines, parallel to the plasma membrane, subjacent to the outer plaque are visible in one third of HDs and are termed sub-basal dense plates (SBDPs). Anchoring filaments traverse the lamina lucida space and appear to insert into the electron dense zone, the lamina densa. Beneath the lamina densa, loop-structured, cross-banded anchoring fibrils extend more than 300 nm beneath the basement membrane within the papillary dermis. The length of these loops may enable them to link or encircle dermal collagen fibers or other components such as those of the elastic microfibril network.	Hemidesmosome # Overview Hemidesmosomes (HD) are very small stud- or rivet-like structures on the inner basal surface of keratinocytes in the epidermis of skin. They are similar in form to desmosomes. The HD comprises two rivet-like plaques (the inner and outer plaques), together with the anchoring fibrils and anchoring filaments these are collectively termed the HD-stable adhesion complex or HD-anchoring filament complex. Together, the HD-anchoring filament complex forms a continuous structural link between the basal keratinocyte keratin intermediate filaments and the underlying basement membrane zone (BMZ) and dermal components. Over the past decade, these structures have been shown to comprise a variety of some 10 or more molecular components. An example configuration of a hemidesmosome might consist of cytosolic keratin, non-covalently bonded to a cytosolic plectin plaque, which is bonded to a single-pass transmembrane adhesion molecule such as the α6β4 integrin. The integrin might then attach to one of many multi-adhesive proteins such as laminin, resident within the extracellular matrix, thereby forming one of many potential adhesions between cell and matrix. Electron microscopic analysis of the epidermal basement membrane zone (BMZ) reveals that it comprises a narrow and sometimes folded interface between the basal keratinocytes and the dermis. At high power, several complex structures are observed within the epidermal BMZ. The epidermal BMZ shows small (< 0.5 micrometers), regularly spaced electron dense structures which are the hemidesmosomes. Thin, extracellular, electron-dense lines, parallel to the plasma membrane, subjacent to the outer plaque are visible in one third of HDs and are termed sub-basal dense plates (SBDPs). Anchoring filaments traverse the lamina lucida space and appear to insert into the electron dense zone, the lamina densa. Beneath the lamina densa, loop-structured, cross-banded anchoring fibrils extend more than 300 nm beneath the basement membrane within the papillary dermis. The length of these loops may enable them to link or encircle dermal collagen fibers or other components such as those of the elastic microfibril network.	https://www.wikidoc.org/index.php/Hemidesmosome
057fffe97664f217e8861bb64253132c272fcc25	wikidoc	Hemoperfusion	Hemoperfusion Hemoperfusion (British English: haemoperfusion) is a medical process used to remove toxic substances from a patients blood. The technique involves passing large volumes of blood over an adsorbent substance. The adsorbent substance most commonly used in hemoperfusion are resins and activated carbon. Hemoperfusion is an extracorporeal form of treatment because the blood is pumped through a device outside the patient's body. Its major uses include removing drugs or poisons from the blood in emergency situations, removing waste products from the blood in patients with renal failure, and as a supportive treatment for patients before and after liver transplantation. # Footnotes - ↑ Rahman MH, Haqqie SS, McGoldrick MD (2006). "Acute hemolysis with acute renal failure in a patient with valproic acid poisoning treated with charcoal hemoperfusion". Hemodialysis international. International Symposium on Home Hemodialysis. 10 (3): 256–9. PMID 16805886.CS1 maint: Multiple names: authors list (link) .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}	Hemoperfusion Hemoperfusion (British English: haemoperfusion) is a medical process used to remove toxic substances from a patients blood. The technique involves passing large volumes of blood over an adsorbent substance. The adsorbent substance most commonly used in hemoperfusion are resins and activated carbon.[1] Hemoperfusion is an extracorporeal form of treatment because the blood is pumped through a device outside the patient's body. Its major uses include removing drugs or poisons from the blood in emergency situations, removing waste products from the blood in patients with renal failure, and as a supportive treatment for patients before and after liver transplantation. # Footnotes - ↑ Rahman MH, Haqqie SS, McGoldrick MD (2006). "Acute hemolysis with acute renal failure in a patient with valproic acid poisoning treated with charcoal hemoperfusion". Hemodialysis international. International Symposium on Home Hemodialysis. 10 (3): 256–9. PMID 16805886.CS1 maint: Multiple names: authors list (link) .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em} Template:Treatment-stub Template:WikiDoc Sources	https://www.wikidoc.org/index.php/Hemoperfusion
96b84035988d4d35876c1d3c89a165fd94a09e47	wikidoc	Herbal viagra	Herbal viagra Herbal viagra is a name that can be given to any herbal product advertised as treating erectile disfunction. The name Herbal viagra is taken from the brand name Viagra, the name under which drug company Pfizer sells Sildenafil citrate, a drug that was designed and is used to treat erectile disfunction. There are many different products being advertised as herbal viagra, all being made with different ingredients. One product, Duro is known to contain an extract of fungus extracted from the larval remains of silkworms. Duro is also said to benefit sportsmen and woman through increased stamina. Many of these herbal remedies originate from ancient tribes, such as Mapuche Viagra which is used by Chile's Mapuche people. Herbal viagras, contrary to what the name suggests, do not normally contain Sildenafil Citrate. Viagra has become a generic term for many people discussing drugs designed to treat erectile disfunction. Herbal viagras often carry a number of dangerous side effects, primarily they often cause abnormally low blood pressure and can restrict blood flow to vital organs. There is also evidence to suggest some preparations may be toxic if taken larger doses. Herbal viagra is predominantly sold through the internet, and in 2003, around 4% or 1 in 25 of all e-mail messages sent offered herbal viagra, genuine pharmaceuticals and other herbal remedies.	Herbal viagra Herbal viagra is a name that can be given to any herbal product advertised as treating erectile disfunction.[1] The name Herbal viagra is taken from the brand name Viagra, the name under which drug company Pfizer sells Sildenafil citrate, a drug that was designed and is used to treat erectile disfunction.[2] There are many different products being advertised as herbal viagra, all being made with different ingredients. One product, Duro is known to contain an extract of fungus extracted from the larval remains of silkworms. Duro is also said to benefit sportsmen and woman through increased stamina.[3] Many of these herbal remedies originate from ancient tribes, such as Mapuche Viagra which is used by Chile's Mapuche people.[4] Herbal viagras, contrary to what the name suggests, do not normally contain Sildenafil Citrate. Viagra has become a generic term for many people discussing drugs designed to treat erectile disfunction.[5] Herbal viagras often carry a number of dangerous side effects, primarily they often cause abnormally low blood pressure and can restrict blood flow to vital organs. There is also evidence to suggest some preparations may be toxic if taken larger doses.[1] Herbal viagra is predominantly sold through the internet, and in 2003, around 4% or 1 in 25 of all e-mail messages sent offered herbal viagra, genuine pharmaceuticals and other herbal remedies.[6]	https://www.wikidoc.org/index.php/Herbal_viagra
345518955674c3c68d9d8728b98ac9f927f363a5	wikidoc	Herd behavior	Herd behavior Herd behaviour describes how individuals in a group can act together without planned direction. The term pertains to the behaviour of animals in herds, flocks, and schools, and to human conduct during activities such as stock market bubbles and crashes, street demonstrations, sporting events, episodes of mob violence and even everyday decision making, judgement and opinion forming. # Herd behaviour in animals A group of animals fleeing a predator shows the nature of herd behavior. In the often cited article "Geometry For The Selfish Herd," evolutionary biologist W. D. Hamilton said each individual group member reduces the danger to itself by moving as close as possible to the center of the fleeing group. Thus the herd appears to act as a unit in moving together, but its function emerges from the uncoordinated behavior of self-seeking individuals. # Symmetry breaking in herding behavior Asymmetric aggregation of animals under panic conditions has been observed in many species, including humans, mice, and ants. Theoretical models have demonstrated symmetry breaking similar to observations in empirical studies. For example when panicked individuals confined to a room with two equal and equidistant exits, a majority will favor one exit while the minority will favor the other. # Possible mechanisms: - Hamilton’s Selfish Herd Theory - Byproduct of communication skill of social animal or runaway positive feedback - Neighbor copying # Escape Panic Characteristics - Individuals attempt to move faster than normal - Interactions between individuals become physical - Exits become arched and clogged - Escape is slowed by fallen individuals serving as obstacles - Individuals display a tendency towards mass or copied behavior - Alternative or less used exits are overlooked # Herd behaviour in human societies Psychological and economic research has identified herd behavior in humans to explain the phenomena of large numbers of people acting in the same way at the same time. The British surgeon Wilfred Trotter popularized the "herd behavior" phrase in his book, Instincts of the Herd in Peace and War (1914). In The Theory of the Leisure Class, Thorstein Veblen explained economic behavior in terms of social influences such as "emulation," where some members of a group mimic other members of higher status. In "The Metropolis and Mental Life" (1903), early sociologist George Simmel referred to the "impulse to sociability in man", and sought to describe "the forms of association by which a mere sum of separate individuals are made into a 'society' ". Other social scientists explored behaviors related to herding, such as Freud (crowd psychology), Carl Jung (collective unconscious), and Gustave Le Bon (the popular mind). Swarm theory observed in non-human societies is a related concept and is being explored as it occurs in human society. ## Stock market bubbles Large stock market trends often begin and end with periods of frenzied buying (bubbles) or selling (crashes). Many observers cite these episodes as clear examples of herding behavior that is irrational and driven by emotion -- greed in the bubbles, fear in the crashes. Individual investors join the crowd of others in a rush to get in or out of the market. Some followers of the technical analysis school of investing see the herding behaviour of investors as an example of extreme market sentiment. The academic study of behavioral finance has identified herding in the collective irrationality of investors, particularly the work of Robert Shiller, and Nobel laureates Vernon Smith, Amos Tversky, and Daniel Kahneman. Hey and Morone (2004) analysed a model of herd behaviour in a market context. Their work is related to at least two important strands of literature. The first of these strands is that on herd behaviour in a non-market context. The seminal references are Banerjee (1992) and Bikhchandani, Hirshleifer and Welch (1992), both of which showed that herd behaviour may result from private information not publicly shared. More specifically, both of these papers showed that individuals, acting sequentially on the basis of private information and public knowledge about the behaviour of others, may end up choosing the socially undesirable option. The second of the strands of literature motivating this paper is that of information aggregation in market contexts. A very early reference is the classic paper by Grossman and Stiglitz (1976) that showed that uninformed traders in a market context can become informed through the price in such a way that private information is aggregated correctly and efficiently. A summary of the progress of this strand of literature can be found in the paper by Plott (2000). Hey and Morone (2004) showed that it is possible to observe herd-type behaviour in a market context. Their result is even more interesting since it refers to a market with a well-defined fundamental value. Even if herd behaviour might only be observed rarely, this has important consequences for a whole range of real markets – most particularly foreign exchange markets. ## Behavior in crowds Crowds that gather on behalf of a grievance can involve herding behavior that turns violent, particularly when confronted by an opposing ethnic or racial group. The Los Angeles riots of 1992, New York Draft Riots and Tulsa Race Riot are notorious in U.S. history, but those episodes are dwarfed by the scale of violence and death during the Partition of India. Population exchanges between India and Pakistan brought millions of migrating Hindus and Muslims into proximity; the ensuing violence produced an estimated death toll of between 200,000 and one million. The idea of a "group mind" or "mob behavior" was put forward by the French social psychologists Gabriel Tarde and Gustav Le Bon. Sporting events can also produce violent episodes of herd behaviour. The most violent single riot in history may be the sixth-century Nika riots in Constantinople, precipitated by partisan factions attending the chariot races. The football hooliganism of the 1980s was a well-publicized, latter-day example of sports violence. ## Everyday decision-making Benign herding behaviors may be frequent in everyday decisions based on learning from the information of others, as when a person on the street decides which of two restaurants to dine in. Suppose that both look appealing, but both are empty because it is early evening; so at random, this person chooses restaurant A. Soon a couple walks down the same street in search of a place to eat. They see that restaurant A has customers while B is empty, and choose A on the assumption that having customers makes it the better choice. And so on with other passersby into the evening, with restaurant A doing more business that night than B. This phenomenon is also referred as an information cascade.	Herd behavior Herd behaviour describes how individuals in a group can act together without planned direction. The term pertains to the behaviour of animals in herds, flocks, and schools, and to human conduct during activities such as stock market bubbles and crashes, street demonstrations, sporting events, episodes of mob violence and even everyday decision making, judgement and opinion forming. # Herd behaviour in animals A group of animals fleeing a predator shows the nature of herd behavior. In the often cited article "Geometry For The Selfish Herd," evolutionary biologist W. D. Hamilton said each individual group member reduces the danger to itself by moving as close as possible to the center of the fleeing group. Thus the herd appears to act as a unit in moving together, but its function emerges from the uncoordinated behavior of self-seeking individuals.[1] # Symmetry breaking in herding behavior Asymmetric aggregation of animals under panic conditions has been observed in many species, including humans, mice, and ants. Theoretical models have demonstrated symmetry breaking similar to observations in empirical studies. For example when panicked individuals confined to a room with two equal and equidistant exits, a majority will favor one exit while the minority will favor the other. # Possible mechanisms: - Hamilton’s Selfish Herd Theory - Byproduct of communication skill of social animal or runaway positive feedback - Neighbor copying # Escape Panic Characteristics - Individuals attempt to move faster than normal - Interactions between individuals become physical - Exits become arched and clogged - Escape is slowed by fallen individuals serving as obstacles - Individuals display a tendency towards mass or copied behavior - Alternative or less used exits are overlooked[1] # Herd behaviour in human societies Psychological and economic research has identified herd behavior in humans to explain the phenomena of large numbers of people acting in the same way at the same time. The British surgeon Wilfred Trotter popularized the "herd behavior" phrase in his book, Instincts of the Herd in Peace and War (1914). In The Theory of the Leisure Class, Thorstein Veblen explained economic behavior in terms of social influences such as "emulation," where some members of a group mimic other members of higher status. In "The Metropolis and Mental Life" (1903), early sociologist George Simmel referred to the "impulse to sociability in man", and sought to describe "the forms of association by which a mere sum of separate individuals are made into a 'society' ". Other social scientists explored behaviors related to herding, such as Freud (crowd psychology), Carl Jung (collective unconscious), and Gustave Le Bon (the popular mind). Swarm theory observed in non-human societies is a related concept and is being explored as it occurs in human society. ## Stock market bubbles Large stock market trends often begin and end with periods of frenzied buying (bubbles) or selling (crashes). Many observers cite these episodes as clear examples of herding behavior that is irrational and driven by emotion -- greed in the bubbles, fear in the crashes. Individual investors join the crowd of others in a rush to get in or out of the market. [2] Some followers of the technical analysis school of investing see the herding behaviour of investors as an example of extreme market sentiment.[3] The academic study of behavioral finance has identified herding in the collective irrationality of investors, particularly the work of Robert Shiller,[4] and Nobel laureates Vernon Smith, Amos Tversky, and Daniel Kahneman. Hey and Morone (2004) analysed a model of herd behaviour in a market context. Their work is related to at least two important strands of literature. The first of these strands is that on herd behaviour in a non-market context. The seminal references are Banerjee (1992) and Bikhchandani, Hirshleifer and Welch (1992), both of which showed that herd behaviour may result from private information not publicly shared. More specifically, both of these papers showed that individuals, acting sequentially on the basis of private information and public knowledge about the behaviour of others, may end up choosing the socially undesirable option. The second of the strands of literature motivating this paper is that of information aggregation in market contexts. A very early reference is the classic paper by Grossman and Stiglitz (1976) that showed that uninformed traders in a market context can become informed through the price in such a way that private information is aggregated correctly and efficiently. A summary of the progress of this strand of literature can be found in the paper by Plott (2000). Hey and Morone (2004) showed that it is possible to observe herd-type behaviour in a market context. Their result is even more interesting since it refers to a market with a well-defined fundamental value. Even if herd behaviour might only be observed rarely, this has important consequences for a whole range of real markets – most particularly foreign exchange markets. ## Behavior in crowds Crowds that gather on behalf of a grievance can involve herding behavior that turns violent, particularly when confronted by an opposing ethnic or racial group. The Los Angeles riots of 1992, New York Draft Riots and Tulsa Race Riot are notorious in U.S. history, but those episodes are dwarfed by the scale of violence and death during the Partition of India. Population exchanges between India and Pakistan brought millions of migrating Hindus and Muslims into proximity; the ensuing violence produced an estimated death toll of between 200,000 and one million. The idea of a "group mind" or "mob behavior" was put forward by the French social psychologists Gabriel Tarde and Gustav Le Bon. Sporting events can also produce violent episodes of herd behaviour. The most violent single riot in history may be the sixth-century Nika riots in Constantinople, precipitated by partisan factions attending the chariot races. The football hooliganism of the 1980s was a well-publicized, latter-day example of sports violence. ## Everyday decision-making Benign herding behaviors may be frequent in everyday decisions based on learning from the information of others, as when a person on the street decides which of two restaurants to dine in. Suppose that both look appealing, but both are empty because it is early evening; so at random, this person chooses restaurant A. Soon a couple walks down the same street in search of a place to eat. They see that restaurant A has customers while B is empty, and choose A on the assumption that having customers makes it the better choice. And so on with other passersby into the evening, with restaurant A doing more business that night than B. This phenomenon is also referred as an information cascade. [5] [6]	https://www.wikidoc.org/index.php/Herd_behavior
a80a15ae692462ea2cd20c179e1dbef3731214b6	wikidoc	Hermaphrodite	Hermaphrodite # Overview A hermaphrodite is an organism having both male and female reproductive organs. In many species, hermaphroditism is a common part of the life-cycle, enabling a form of sexual reproduction in which the two sexes are not separated into distinct male and female types of individual. Hermaphroditism most commonly occurs in invertebrates, although it is also found in some fish, and to a lesser degree in other vertebrates. Historically, the term hermaphrodite has also been used to describe ambiguous genitalia and gonadal mosaicism in individuals of gonochoristic species, especially human beings. The term comes from the name of the minor Greek god Hermaphroditus, son of Hermes and Aphrodite (see below). Recently, intersex has been used and preferred by many such individuals, encouraging medical professionals to use the term. # Zoology ## Sequential hermaphrodites Sequential hermaphrodites (dichogamy) occurs in species in which the individual is born as one sex but can later change into the alternate sex. This is in contrast with simultaneous hermaphrodites, in which an individual may possess fully functional male and female gonads. Sequential hermaphroditism is common in teleost fish, especially marine reef species. While some sequential hermaphrodites can change sex multiple times, most can only change sex once. Sequential hermaphrodites fall into two broad categories: - Protandry: Where the organism is born as a male, and then changes sex to a female. Example: The Clownfish (Genus Amphiprion) are colorful reef fish found living in symbiosis with anemones. Generally one anemone contains a 'harem', consisting of a large female, a smaller reproductive male, and even smaller non-reproductive males. If the female is removed, the reproductive male will change sex and the largest of the non-reproductive males will mature and become reproductive. It has been shown that fishing pressure can change when the switch from male to female occurs, since fishermen naturally prefer to catch the larger fish. The populations are generally changing sex at a smaller size, due to artificial selection. - Example: The Clownfish (Genus Amphiprion) are colorful reef fish found living in symbiosis with anemones. Generally one anemone contains a 'harem', consisting of a large female, a smaller reproductive male, and even smaller non-reproductive males. If the female is removed, the reproductive male will change sex and the largest of the non-reproductive males will mature and become reproductive. It has been shown that fishing pressure can change when the switch from male to female occurs, since fishermen naturally prefer to catch the larger fish. The populations are generally changing sex at a smaller size, due to artificial selection. - Protogyny: Where the organism starts as a female, and then changes sex to a male. Example: Wrasses (Family Labridae) are a group of reef fish in which protogyny is common. Wrasses also have an uncommon life history strategy, which is termed diandry (literally, two males). In these species, two male morphs exists: an initial phase male or a terminal phase male. Initial phase males do not look like males and spawn in groups with other females. They are not territorial. They are perhaps, female mimics (which is why they are found swimming in group with other females). Terminal phase males are territorial, and have a distinctively bright coloration. Individuals are born as males or females but if they are born males, they are not born as Terminal Phase males. Females and initial phase males can become terminal phase males. Usually the most dominant female or initial phase male replaces any terminal phase male, when those males die or abandon the group. - Example: Wrasses (Family Labridae) are a group of reef fish in which protogyny is common. Wrasses also have an uncommon life history strategy, which is termed diandry (literally, two males). In these species, two male morphs exists: an initial phase male or a terminal phase male. Initial phase males do not look like males and spawn in groups with other females. They are not territorial. They are perhaps, female mimics (which is why they are found swimming in group with other females). Terminal phase males are territorial, and have a distinctively bright coloration. Individuals are born as males or females but if they are born males, they are not born as Terminal Phase males. Females and initial phase males can become terminal phase males. Usually the most dominant female or initial phase male replaces any terminal phase male, when those males die or abandon the group. Sequential hermaphrodites possess an ambisexual gonad. The gonad has both a male and a female portion. When an individual changes sex, gonad remodeling occurs. Interestingly, changes in behavior often occur before these gonad changes. ## Simultaneous hermaphrodites A simultaneous hermaphrodite (or synchronous hermaphrodite) is an adult organism that has both male and female sexual organs at the same time. Usually, self-fertilization does not occur. - Snails are perhaps the most classic of simultaneous hermaphrodite, and the most widespread of terrestrial animals possessing this sexual polymorphism. Using calcium carbonate 'arrows' as sperm carriers which are exchanged between snails by shooting them, sexual material is exchanged between both animals. In this way, snails have been poetically compared with Cupid for their sharing of shooting 'Arrows of Love'. After exchange of spermatazoa, both animals will lay fertilized eggs after a period of gestation, which then proceed to hatch after a development period. Snails typically reproduce in early spring and late autumn. - Hamlets, unlike other fish, seem quite at ease mating in front of divers, allowing observations in the wild to occur readily. They do not practice self-fertilization, but when they find a mate, the pair takes turns between which one acts as the male and which acts as the female through multiple matings, usually over the course of several nights. - Earthworms are another example of a simultaneous hermaphrodite. Although they possess ovaries and testes, they have a protective mechanism against self fertilization and can only function as a single sex at one time. Sexual reproduction occurs when two worms meet and exchange gametes, copulating on damp nights during warm seasons. Fertilized eggs are protected by a cocoon, which is buried on or near the surface of the ground. - Banana Slugs are one more simultaneous hermaphrodite example. Mating with a partner is most desirable, as the genetic material of the offspring is varied, but if mating with a partner is not possible, self-fertilization is practised. The male sexual organ of an adult banana slug is quite large in proportion to its size, as well as compared to the female organ. It is possible for banana slugs, while mating, to become stuck together. If a substantial amount of wiggling fails to separate them, the male's organ will be bitten off (with the slug's radula). If a banana slug has lost its male sexual organ, it can still self-fertilize, making its hermaphroditic quality an invaluable adaptation. ## Other Hyenas have a clitoris that is greatly enlarged, so much so, that they were described as hermaphrodites -- not only by the ancient Greeks, but as recently as the twentieth century among circus animal handlers -- until scientific information was provided that clarified the misunderstanding. # Botany Hermaphrodite is used in botany to describe a flower that has both staminate (male, pollen-producing) and carpellate (female, ovule-producing) parts. This condition is seen in many common garden plants. A closer analogy to hermaphrodism in animals is the presence of separate male and female flowers on the same individual—such plants are called monoecious. Monoecy is especially common in conifers, but occurs in only about 7% of angiosperm species (Molnar, 2004). # Other uses of the term Hermaphrodite was used to describe any person incompatible with the biological gender binary, but has recently been replaced by intersexual in medicine. Humans with typical reproductive organs but atypical clitoris/penis are called pseudohermaphrodites in medical literature. Whether hermaphroditism is a disorder or merely an unusual condition is a matter of opinion. In most societies, the common assumption is that all people are, or at least should be, either male or female. This assumption can make life difficult for hermaphrodites. People with intersex conditions sometimes choose to live exclusively as one sex or the other, using clothing, social cues, genital surgery, and hormone replacement therapy to blend into the sex they identify with more closely. Some people who are intersexed, such as some of those with Klinefelter's syndrome and androgen insensitivity syndrome, outwardly appear completely female or male already, without realizing they are intersexed. Other kinds of intersex conditions are identified immediately at birth because those with the condition have a sexual organ larger than a clitoris and smaller than a penis. Intersexuality is thought by some to be caused by unusual sex hormones; the unusual hormones may be caused by an atypical set of sex chromosomes. Sigmund Freud (based on work by his associate Wilhelm Fliess) held fetal hermaphroditism to be a fact of the physiological development of humans. He was so certain of this, in fact, that he based much of his theory of innate sexuality on that assumption. Similarly, in contemporary times, fetuses before sexual differentiation are sometimes described as female by doctors explaining the process. Neither concept is technically true. Before this stage, humans are simply undifferentiated and possess a Müllerian duct, a Wolffian duct, and a genital tubercle. # Etymology The term "hermaphrodite" derives from Hermaphroditus, the son of Hermes and Aphrodite in Greek mythology, who was fused with a nymph, Salmacis, resulting in one individual possessing physical traits of both genders. Thus Hermaphroditus could be called, using modern terminology, a simultaneous hermaphrodite. The mythological figure of Tiresias, who figures in the Oedipus cycle as well as the Odyssey, could be called a sequential hermaphrodite, having been changed from a man to a woman and back by the gods. # Gallery - Hermaphrodite. With permission of Dermatology Atlas'	Hermaphrodite Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview A hermaphrodite is an organism having both male and female reproductive organs.[1] In many species, hermaphroditism is a common part of the life-cycle, enabling a form of sexual reproduction in which the two sexes are not separated into distinct male and female types of individual. Hermaphroditism most commonly occurs in invertebrates, although it is also found in some fish, and to a lesser degree in other vertebrates. Historically, the term hermaphrodite has also been used to describe ambiguous genitalia and gonadal mosaicism in individuals of gonochoristic species, especially human beings. The term comes from the name of the minor Greek god Hermaphroditus, son of Hermes and Aphrodite (see below). Recently, intersex has been used and preferred by many such individuals, encouraging medical professionals to use the term.[2] # Zoology ## Sequential hermaphrodites Sequential hermaphrodites (dichogamy) occurs in species in which the individual is born as one sex but can later change into the alternate sex. This is in contrast with simultaneous hermaphrodites, in which an individual may possess fully functional male and female gonads. Sequential hermaphroditism is common in teleost fish, especially marine reef species. While some sequential hermaphrodites can change sex multiple times, most can only change sex once. Sequential hermaphrodites fall into two broad categories: - Protandry: Where the organism is born as a male, and then changes sex to a female. Example: The Clownfish (Genus Amphiprion) are colorful reef fish found living in symbiosis with anemones. Generally one anemone contains a 'harem', consisting of a large female, a smaller reproductive male, and even smaller non-reproductive males. If the female is removed, the reproductive male will change sex and the largest of the non-reproductive males will mature and become reproductive. It has been shown that fishing pressure can change when the switch from male to female occurs, since fishermen naturally prefer to catch the larger fish. The populations are generally changing sex at a smaller size, due to artificial selection. - Example: The Clownfish (Genus Amphiprion) are colorful reef fish found living in symbiosis with anemones. Generally one anemone contains a 'harem', consisting of a large female, a smaller reproductive male, and even smaller non-reproductive males. If the female is removed, the reproductive male will change sex and the largest of the non-reproductive males will mature and become reproductive. It has been shown that fishing pressure can change when the switch from male to female occurs, since fishermen naturally prefer to catch the larger fish. The populations are generally changing sex at a smaller size, due to artificial selection. - Protogyny: Where the organism starts as a female, and then changes sex to a male. Example: Wrasses (Family Labridae) are a group of reef fish in which protogyny is common. Wrasses also have an uncommon life history strategy, which is termed diandry (literally, two males). In these species, two male morphs exists: an initial phase male or a terminal phase male. Initial phase males do not look like males and spawn in groups with other females. They are not territorial. They are perhaps, female mimics (which is why they are found swimming in group with other females). Terminal phase males are territorial, and have a distinctively bright coloration. Individuals are born as males or females but if they are born males, they are not born as Terminal Phase males. Females and initial phase males can become terminal phase males. Usually the most dominant female or initial phase male replaces any terminal phase male, when those males die or abandon the group. - Example: Wrasses (Family Labridae) are a group of reef fish in which protogyny is common. Wrasses also have an uncommon life history strategy, which is termed diandry (literally, two males). In these species, two male morphs exists: an initial phase male or a terminal phase male. Initial phase males do not look like males and spawn in groups with other females. They are not territorial. They are perhaps, female mimics (which is why they are found swimming in group with other females). Terminal phase males are territorial, and have a distinctively bright coloration. Individuals are born as males or females but if they are born males, they are not born as Terminal Phase males. Females and initial phase males can become terminal phase males. Usually the most dominant female or initial phase male replaces any terminal phase male, when those males die or abandon the group. Sequential hermaphrodites possess an ambisexual gonad. The gonad has both a male and a female portion. When an individual changes sex, gonad remodeling occurs. Interestingly, changes in behavior often occur before these gonad changes. ## Simultaneous hermaphrodites A simultaneous hermaphrodite (or synchronous hermaphrodite) is an adult organism that has both male and female sexual organs at the same time. Usually, self-fertilization does not occur. - Snails are perhaps the most classic of simultaneous hermaphrodite, and the most widespread of terrestrial animals possessing this sexual polymorphism. Using calcium carbonate 'arrows' as sperm carriers which are exchanged between snails by shooting them, sexual material is exchanged between both animals. In this way, snails have been poetically compared with Cupid for their sharing of shooting 'Arrows of Love'. After exchange of spermatazoa, both animals will lay fertilized eggs after a period of gestation, which then proceed to hatch after a development period. Snails typically reproduce in early spring and late autumn. - Hamlets, unlike other fish, seem quite at ease mating in front of divers, allowing observations in the wild to occur readily. They do not practice self-fertilization, but when they find a mate, the pair takes turns between which one acts as the male and which acts as the female through multiple matings, usually over the course of several nights. - Earthworms are another example of a simultaneous hermaphrodite. Although they possess ovaries and testes, they have a protective mechanism against self fertilization and can only function as a single sex at one time. Sexual reproduction occurs when two worms meet and exchange gametes, copulating on damp nights during warm seasons. Fertilized eggs are protected by a cocoon, which is buried on or near the surface of the ground. - Banana Slugs are one more simultaneous hermaphrodite example. Mating with a partner is most desirable, as the genetic material of the offspring is varied, but if mating with a partner is not possible, self-fertilization is practised. The male sexual organ of an adult banana slug is quite large in proportion to its size, as well as compared to the female organ. It is possible for banana slugs, while mating, to become stuck together. If a substantial amount of wiggling fails to separate them, the male's organ will be bitten off (with the slug's radula). If a banana slug has lost its male sexual organ, it can still self-fertilize, making its hermaphroditic quality an invaluable adaptation. ## Other Hyenas have a clitoris that is greatly enlarged, so much so, that they were described as hermaphrodites -- not only by the ancient Greeks, but as recently as the twentieth century among circus animal handlers -- until scientific information was provided that clarified the misunderstanding. # Botany Hermaphrodite is used in botany to describe a flower that has both staminate (male, pollen-producing) and carpellate (female, ovule-producing) parts. This condition is seen in many common garden plants. A closer analogy to hermaphrodism in animals is the presence of separate male and female flowers on the same individual—such plants are called monoecious. Monoecy is especially common in conifers, but occurs in only about 7% of angiosperm species (Molnar, 2004). # Other uses of the term Hermaphrodite was used to describe any person incompatible with the biological gender binary, but has recently been replaced by intersexual in medicine. Humans with typical reproductive organs but atypical clitoris/penis are called pseudohermaphrodites in medical literature. Whether hermaphroditism is a disorder or merely an unusual condition is a matter of opinion. In most societies, the common assumption is that all people are, or at least should be, either male or female. This assumption can make life difficult for hermaphrodites. People with intersex conditions sometimes choose to live exclusively as one sex or the other, using clothing, social cues, genital surgery, and hormone replacement therapy to blend into the sex they identify with more closely. Some people who are intersexed, such as some of those with Klinefelter's syndrome and androgen insensitivity syndrome, outwardly appear completely female or male already, without realizing they are intersexed. Other kinds of intersex conditions are identified immediately at birth because those with the condition have a sexual organ larger than a clitoris and smaller than a penis. Intersexuality is thought by some to be caused by unusual sex hormones; the unusual hormones may be caused by an atypical set of sex chromosomes. Sigmund Freud (based on work by his associate Wilhelm Fliess) held fetal hermaphroditism to be a fact of the physiological development of humans. He was so certain of this, in fact, that he based much of his theory of innate sexuality on that assumption. Similarly, in contemporary times, fetuses before sexual differentiation are sometimes described as female by doctors explaining the process.[3] Neither concept is technically true. Before this stage, humans are simply undifferentiated and possess a Müllerian duct, a Wolffian duct, and a genital tubercle. # Etymology The term "hermaphrodite" derives from Hermaphroditus, the son of Hermes and Aphrodite in Greek mythology, who was fused with a nymph, Salmacis, resulting in one individual possessing physical traits of both genders. Thus Hermaphroditus could be called, using modern terminology, a simultaneous hermaphrodite. The mythological figure of Tiresias, who figures in the Oedipus cycle as well as the Odyssey, could be called a sequential hermaphrodite, having been changed from a man to a woman and back by the gods. # Gallery - Hermaphrodite. With permission of Dermatology Atlas'	https://www.wikidoc.org/index.php/Hermaphrodite
dd0f22b6e9bda5144782aa8e73e5a47f3d47d762	wikidoc	Hermetic seal	Hermetic seal A hermetic seal is a seal which, for practical purposes, is considered airtight. For example, tin cans are hermetically sealed. The term is often used to describe electronic parts that are designed and intended to secure against the entry of microorganisms and to maintain the safety and quality of their contents. Applications include semiconductor electronics, thermostats, optical devices, and switches. The food, chemical, and pharmaceutical industries all have applications for the use of such "airtight" packaging, such as glass, metals, and high barrier plastics (with effective heat seals). High-end coffins / caskets, too, are often made to be "hermetically sealed" and must be of metal or of other material with metal lining, and constructed so that when closed and fastened the coffin is completely airtight. In some nuclear reactor designs, the reactor is housed in a hermetically sealed reactor vessel. The expression "hermetically sealed" finds its roots in Hermes Trismegistus, a syncretism of the Greek god Hermes and the Egyptian god of wisdom, Thoth. Its origin can be traced back to about 300 AD. Hermes Trismegistus purportedly authored several books containing secrets of alchemy and mystic philosophy, the Hermetica. In the 17th century, English writers began using the adjective hermetic to refer to things that were sealed or secret. An early "hermetically sealed" container featured in the dramatic demonstration of the force of air pressure in creating a hermetic seal in 1663, when for the enlightenment and entertainment of the court of Friedrich Wilhelm I of Brandenburg, Otto von Guericke joined two copper hemispheres (Magdeburg hemispheres) and pumped the air out of the enclosure. Then he harnessed a team of eight horses to each hemisphere and showed that they were not able to separate them. In 1951, The U.S. Constitution, U.S. Declaration of Independence and U.S. Bill of Rights were hermetically sealed with helium gas in glass cases housed in the U.S. National Archives in Washington, DC. In 2003, they were hermetically sealed with argon gas in glass cases. # Etymology The word hermetic comes from the syncretism of the Greek god Hermes and the Egyptian Thoth; this figure was also a mythological alchemist known as Hermes Trismegistus. The latter has two books attributed to him, the Emerald Tablet and the Corpus Hermeticum. He was believed to possess a magic ability to seal treasure chests so that nothing could access their contents. Alchemists also frequently used distillation in their experiments, and needed an airtight seal to improve the efficiency of their alembic stills. Most alchemists, though, were considered to be Hermetics for adopting the philosophy of the Emerald Tablet or the Corpus Hermeticum.	Hermetic seal A hermetic seal is a seal which, for practical purposes, is considered airtight. For example, tin cans are hermetically sealed. The term is often used to describe electronic parts that are designed and intended to secure against the entry of microorganisms and to maintain the safety and quality of their contents. Applications include semiconductor electronics, thermostats, optical devices, and switches. The food, chemical, and pharmaceutical industries all have applications for the use of such "airtight" packaging, such as glass, metals, and high barrier plastics (with effective heat seals). High-end coffins / caskets, too, are often made to be "hermetically sealed" and must be of metal or of other material with metal lining, and constructed so that when closed and fastened the coffin is completely airtight. In some nuclear reactor designs, the reactor is housed in a hermetically sealed reactor vessel. The expression "hermetically sealed" finds its roots in Hermes Trismegistus, a syncretism of the Greek god Hermes and the Egyptian god of wisdom, Thoth. Its origin can be traced back to about 300 AD. Hermes Trismegistus purportedly authored several books containing secrets of alchemy and mystic philosophy, the Hermetica. In the 17th century, English writers began using the adjective hermetic to refer to things that were sealed or secret. An early "hermetically sealed" container featured in the dramatic demonstration of the force of air pressure in creating a hermetic seal in 1663, when for the enlightenment and entertainment of the court of Friedrich Wilhelm I of Brandenburg, Otto von Guericke joined two copper hemispheres (Magdeburg hemispheres) and pumped the air out of the enclosure. Then he harnessed a team of eight horses to each hemisphere and showed that they were not able to separate them. In 1951, The U.S. Constitution, U.S. Declaration of Independence and U.S. Bill of Rights were hermetically sealed with helium gas in glass cases housed in the U.S. National Archives in Washington, DC. In 2003, they were hermetically sealed with argon gas in glass cases.[1] # Etymology The word hermetic comes from the syncretism of the Greek god Hermes and the Egyptian Thoth; this figure was also a mythological alchemist known as Hermes Trismegistus. The latter has two books attributed to him, the Emerald Tablet and the Corpus Hermeticum. He was believed to possess a magic ability to seal treasure chests so that nothing could access their contents. Alchemists also frequently used distillation in their experiments, and needed an airtight seal to improve the efficiency of their alembic stills. Most alchemists, though, were considered to be Hermetics for adopting the philosophy of the Emerald Tablet or the Corpus Hermeticum. # External links - Hermetic Sealing with Laser Technology	https://www.wikidoc.org/index.php/Hermetic_seal
e7622369c642802e663f2eda2ff601487761eed3	wikidoc	Herniorrhaphy	Herniorrhaphy # Overview Herniorrhaphy (Hernioplasty, Hernia repair) is a surgical procedure for correcting hernia. A hernia is a bulging of internal organs or tissues, which protrude through an abnormal opening in the muscle wall. Hernias can occur in the abdomen, groin, and at the site of a previous surgery. # Techniques Herniorraphy, or hernioplasty, is now often performed as an ambulatory, or "day surgery," procedure. Almost 700,000 are performed each year in the United States. These techniques can be divided into four groups. ## Groups 1 and 2: open "tension" repair A workable technique of repairing hernia was first described by Bassini in the 1800s; the Bassini technique was a "tension" repair, in which the edges of the defect are sewn back together without any reinforcement or prosthesis. In the Bassini technique, the conjoint tendon (formed by the distal ends of the transversus abdominis muscle and the internal oblique muscle) is approximated to the inguinal canal and closed. Although tension repairs are no longer the standard of care due to the high rate of recurrence of the hernia, long recovery period, and post-operative pain, a few tension repairs are still in use today; these include the Shouldice and the Cooper's ligament/McVay repair. The Shouldice techniques is a complicated four layer reconstruction, however, it has relatively low reported recurrence rates. An operation in which the hernia sac is removed in addition to tension repair is described as a 'herniotomy'. ## Group 3: open "tension-free" repair Almost all repairs done today are open "tension-free" repairs that involve the placement of a synthetic mesh to strengthen the inguinal region; some popular techniques include the Lichtenstein repair (flat mesh patch placed on top of the defect), Plug and Patch (mesh plug placed in the defect and covered by a Lichtenstein-type patch), Kugel (mesh device placed behind the defect), and Prolene Hernia System (2-layer mesh device placed over and behind the defect). This operation is called a 'hernioplasty'. The meshes used are typically made from polypropylene or polyester, although some companies market Teflon meshes and partially absorbable meshes. The operation is typically performed under local anesthesia, and patients go home within a few hours of surgery, often requiring no medication beyond aspirin or acetaminophen. Patients are encouraged to walk and move around immediately post-operatively, and can usually resume all their normal activities within a week or two of operation. Recurrence rates are very low - one percent or less, compared with over 10% for a tension repair. Rates of complications are generally low but they can be quite serious, and can include chronic pain, ischemic orchitis, and testicular atrophy. ## Group 4: laparoscopic repair In recent years, as in other areas of surgery, laparoscopic repair of inguinal hernia has emerged as an option. "Lap" repairs are also tension-free, although the mesh is placed within the preperitoneal space behind the defect as opposed to in or over it. It has no proven superiority to the open method other than a faster recovery time and a slightly lower post-operative pain score. Unlike the open method, laparoscopic surgery requires general anesthesia. It is usually more expensive and consumes more O.R. time than open repair, carries a higher risk of complications, and has equivalent or higher rates of recurrence compared to the open tension-free repairs. ## Comparisons In the UK a government committee called NICE re-examined the data on laparoscopic and open repair (2004). They concluded that there is no difference in cost, as the increased costs of operation are offset by the decreased recovery period. Recurrence rates are identical. They found that laparoscopic repair results in a more rapid recovery and less pain in the first few days. They found that lap repair has less risk of wound infection, less bleeding and less swelling after surgery (seroma). They also reported less chronic pain, which can last for years and in one in 30 patients can be severe. A recent, large American study found that recurrence within two years of operation after lap repair was 10% compared with 4% after open surgery. Both of these results however are considered poor by international standards and suggest that the surgeons were inexperienced, particularly in lap repair. Open mesh repair or laporascopic mesh repair are good and have shown reduced recurrences or early recovery. Complications related to the use of mesh include infection, mesh migration, adhesion formation, erosion into intraperitoneal organs, and chronic pain - due probably to entrapment of nerves, vessels or the vas deferens. Such complications usually become apparent weeks to years after the initial repair, presenting as abscess, fistula, or small bowel obstruction. More recently, concerns have been raised about the possibility of obstruction of the vas deferens as a result of the fibroblastic reaction to the mesh. ## Dr. Desarda's repair Recently introduced "Dr.Desarda's repair" is without mesh or any foreign body. Even sutures used are absorbable, a thing which was never imagined till today. An undetached strip of the external oblique aponeurosis goes behind the cord to form a new posterior wall between the inguinal ligament and the muscle arch. There are no recurrences, no pain, patient can drive a car and go to office in 3-4 day. The claims of novelty and significance of this approach have, however, been questioned by some. Readers are requested to go through the reply given by the author of this new technique to some one who questioned.	Herniorrhaphy # Overview Template:Interventions infobox Herniorrhaphy (Hernioplasty, Hernia repair) is a surgical procedure for correcting hernia. A hernia is a bulging of internal organs or tissues, which protrude through an abnormal opening in the muscle wall. Hernias can occur in the abdomen, groin, and at the site of a previous surgery. # Techniques Herniorraphy, or hernioplasty, is now often performed as an ambulatory, or "day surgery," procedure. Almost 700,000 are performed each year in the United States. These techniques can be divided into four groups.[1] ## Groups 1 and 2: open "tension" repair A workable technique of repairing hernia was first described by Bassini in the 1800s;[2][3] the Bassini technique was a "tension" repair, in which the edges of the defect are sewn back together without any reinforcement or prosthesis. In the Bassini technique, the conjoint tendon (formed by the distal ends of the transversus abdominis muscle and the internal oblique muscle) is approximated to the inguinal canal and closed. [4] Although tension repairs are no longer the standard of care due to the high rate of recurrence of the hernia, long recovery period, and post-operative pain, a few tension repairs are still in use today; these include the Shouldice and the Cooper's ligament/McVay repair.[5] [6] The Shouldice techniques is a complicated four layer reconstruction, however, it has relatively low reported recurrence rates.[7] An operation in which the hernia sac is removed in addition to tension repair is described as a 'herniotomy'. ## Group 3: open "tension-free" repair Almost all repairs done today are open "tension-free" repairs that involve the placement of a synthetic mesh to strengthen the inguinal region; some popular techniques include the Lichtenstein repair (flat mesh patch placed on top of the defect)[8], Plug and Patch (mesh plug placed in the defect and covered by a Lichtenstein-type patch), Kugel (mesh device placed behind the defect), and Prolene Hernia System (2-layer mesh device placed over and behind the defect). This operation is called a 'hernioplasty'. The meshes used are typically made from polypropylene or polyester, although some companies market Teflon meshes and partially absorbable meshes. The operation is typically performed under local anesthesia, and patients go home within a few hours of surgery, often requiring no medication beyond aspirin or acetaminophen. Patients are encouraged to walk and move around immediately post-operatively, and can usually resume all their normal activities within a week or two of operation. Recurrence rates are very low - one percent or less, compared with over 10% for a tension repair. Rates of complications are generally low but they can be quite serious, and can include chronic pain, ischemic orchitis, and testicular atrophy.[9][10] ## Group 4: laparoscopic repair In recent years, as in other areas of surgery, laparoscopic repair of inguinal hernia has emerged as an option. "Lap" repairs are also tension-free, although the mesh is placed within the preperitoneal space behind the defect as opposed to in or over it. It has no proven superiority to the open method other than a faster recovery time and a slightly lower post-operative pain score. Unlike the open method, laparoscopic surgery requires general anesthesia. It is usually more expensive and consumes more O.R. time than open repair, carries a higher risk of complications, and has equivalent or higher rates of recurrence compared to the open tension-free repairs. ## Comparisons In the UK a government committee called NICE[11] re-examined the data on laparoscopic and open repair (2004). They concluded that there is no difference in cost, as the increased costs of operation are offset by the decreased recovery period. Recurrence rates are identical. They found that laparoscopic repair results in a more rapid recovery and less pain in the first few days. They found that lap repair has less risk of wound infection, less bleeding and less swelling after surgery (seroma). They also reported less chronic pain, which can last for years and in one in 30 patients can be severe. A recent, large American study[12] found that recurrence within two years of operation after lap repair was 10% compared with 4% after open surgery. Both of these results however are considered poor by international standards and suggest that the surgeons were inexperienced, particularly in lap repair. Open mesh repair or laporascopic mesh repair are good and have shown reduced recurrences or early recovery. Complications related to the use of mesh include infection, mesh migration, adhesion formation, erosion into intraperitoneal organs, and chronic pain - due probably to entrapment of nerves, vessels or the vas deferens.[13] Such complications usually become apparent weeks to years after the initial repair, presenting as abscess, fistula, or small bowel obstruction.[14][15] More recently, concerns have been raised about the possibility of obstruction of the vas deferens as a result of the fibroblastic reaction to the mesh.[16][17] ## Dr. Desarda's repair Recently introduced "Dr.Desarda's repair" is without mesh or any foreign body.[18][19] Even sutures used are absorbable, a thing which was never imagined till today. An undetached strip of the external oblique aponeurosis goes behind the cord to form a new posterior wall between the inguinal ligament and the muscle arch. There are no recurrences, no pain, patient can drive a car and go to office in 3-4 day. The claims of novelty and significance of this approach have, however, been questioned by some.[20] Readers are requested to go through the reply given by the author of this new technique to some one who questioned. [21]	https://www.wikidoc.org/index.php/Hernia_repair
016dc3204a295bc5606c55085df7401a894f5fc2	wikidoc	Herpesviridae	Herpesviridae # Overview The Herpesviridae are a large family of DNA viruses that cause diseases in humans and animals. The family name is derived from the Greek word herpein ("to creep"), referring to the latent, re-occurring infections typical of this group of viruses. Herpesviridae can cause latent or lytic infections. # Human herpesviridae There are eight distinct viruses in this family known to cause disease in humans. Monkey B virus (Cercopithecine herpesvirus-1, Herpesvirus simiae) is a simplexvirus endemic in macaque monkeys. Human zoonotic infection typically results in fatal encephalomyelitis or severe neurologic impairment in untreated individuals. ## Viral structure The human herpesviruses all share some common properties. One shared property is virus structure - all herpesviruses are composed of relatively large double-stranded, linear DNA genomes encoding 100-200 genes encased within an icosahedral protein cage called the capsid which is itself wrapped in a lipid bilayer membrane called the envelope. This particle is known as the virion. Following binding of viral envelope glycoproteins to cell membrane receptors, the virion is internalized and dismantled, allowing viral DNA to migrate to the cell nucleus. Within the nucleus, viral DNA limited replication and transcription of viral genes. During symptomatic infection, infected cells transcribe lytic viral genes. In some host cells, a small number of viral genes termed latency associated transcript (LAT) accumulate instead. In this fashion the virus can persist in the cell (and thus the host) indefinitely. Reactivation of latent viruses has been implicated in a number of organic diseases. While primary infection is often accompanied by a self-limited period of clinical illness, long-term latency is symptom-free. Following activation, transcription of viral genes switches from LAT to multiple lytic genes that lead to enhanced replication and virus production. Often, lytic activation leads to cell death. Clinically, lytic activation is often accompanied by emergence of non-specific symptoms such as low grade fever, headache, sore throat, malaise, and rash as well as clinical signs such as swollen or tender lymph nodes and immunological findings such as reduced levels of natural killer cells. # Animal herpesviridae - Subfamily Alphaherpesvirinae Genus Simplexvirus Bovine herpesvirus 2 causes bovine mammillitis and pseudo-lumpyskin disease. Cercopithecine herpesvirus 1, also known as Herpes B virus, causes a Herpes simplex-like disease in Macaques. Ateline herpesvirus 1, Spider monkey herpesvirus. Genus Varicellovirus Bovine herpesvirus 1 causes infectious bovine rhinotracheitis, vaginitis, balanoposthitis, and abortion in cattle. Bovine herpesvirus 5 causes encephalitis in cattle. Caprine herpesvirus 1 causes conjunctivitis and respiratory disease in goats. Porcine herpesvirus 1 causes pseudorabies. Equine herpesvirus 1 causes abortion in horses. Equine herpesvirus 3 causes coital exanthema in horses. Equine herpesvirus 4 causes rhinopneumonitis in horses. Canine herpesvirus 1 causes a severe hemorrhagic disease in puppies. Feline herpesvirus 1 causes feline viral rhinotracheitis and keratitis in cats. Duck herpesvirus 1 causes duck plague. Genus Mardivirus Gallid herpesvirus 2 causes Marek's disease. Gallid herpesvirus 3 (GaHV-3 or MDV-2) Herpesvirus of turkeys (HVT) Genus Iltovirus Gallid herpesvirus 1 causes infectious laryngotracheitis in birds. - Genus Simplexvirus Bovine herpesvirus 2 causes bovine mammillitis and pseudo-lumpyskin disease. Cercopithecine herpesvirus 1, also known as Herpes B virus, causes a Herpes simplex-like disease in Macaques. Ateline herpesvirus 1, Spider monkey herpesvirus. - Bovine herpesvirus 2 causes bovine mammillitis and pseudo-lumpyskin disease. - Cercopithecine herpesvirus 1, also known as Herpes B virus, causes a Herpes simplex-like disease in Macaques. - Ateline herpesvirus 1, Spider monkey herpesvirus. - Genus Varicellovirus Bovine herpesvirus 1 causes infectious bovine rhinotracheitis, vaginitis, balanoposthitis, and abortion in cattle. Bovine herpesvirus 5 causes encephalitis in cattle. Caprine herpesvirus 1 causes conjunctivitis and respiratory disease in goats. Porcine herpesvirus 1 causes pseudorabies. Equine herpesvirus 1 causes abortion in horses. Equine herpesvirus 3 causes coital exanthema in horses. Equine herpesvirus 4 causes rhinopneumonitis in horses. Canine herpesvirus 1 causes a severe hemorrhagic disease in puppies. Feline herpesvirus 1 causes feline viral rhinotracheitis and keratitis in cats. Duck herpesvirus 1 causes duck plague. - Bovine herpesvirus 1 causes infectious bovine rhinotracheitis, vaginitis, balanoposthitis, and abortion in cattle. - Bovine herpesvirus 5 causes encephalitis in cattle. - Caprine herpesvirus 1 causes conjunctivitis and respiratory disease in goats. - Porcine herpesvirus 1 causes pseudorabies. - Equine herpesvirus 1 causes abortion in horses. - Equine herpesvirus 3 causes coital exanthema in horses. - Equine herpesvirus 4 causes rhinopneumonitis in horses. - Canine herpesvirus 1 causes a severe hemorrhagic disease in puppies. - Feline herpesvirus 1 causes feline viral rhinotracheitis and keratitis in cats. - Duck herpesvirus 1 causes duck plague. - Genus Mardivirus Gallid herpesvirus 2 causes Marek's disease. Gallid herpesvirus 3 (GaHV-3 or MDV-2) Herpesvirus of turkeys (HVT) - Gallid herpesvirus 2 causes Marek's disease. - Gallid herpesvirus 3 (GaHV-3 or MDV-2) - Herpesvirus of turkeys (HVT) - Genus Iltovirus Gallid herpesvirus 1 causes infectious laryngotracheitis in birds. - Gallid herpesvirus 1 causes infectious laryngotracheitis in birds. - Subfamily Betaherpesvirinae Porcine herpesvirus 2 causes inclusion body rhinitis in swine. - Porcine herpesvirus 2 causes inclusion body rhinitis in swine. - Subfamily Gammaherpesvirinae Genus Rhadinovirus Alcelaphine herpesvirus 1 causes bovine malignant catarrhal fever. Bovine herpesvirus 4 Equine herpesvirus 2 causes equine cytomegalovirus infection. Equine herpesvirus 5 - Genus Rhadinovirus Alcelaphine herpesvirus 1 causes bovine malignant catarrhal fever. Bovine herpesvirus 4 Equine herpesvirus 2 causes equine cytomegalovirus infection. Equine herpesvirus 5 - Alcelaphine herpesvirus 1 causes bovine malignant catarrhal fever. - Bovine herpesvirus 4 - Equine herpesvirus 2 causes equine cytomegalovirus infection. - Equine herpesvirus 5 # Taxonomy The following genera are included here: - Subfamily Alphaherpesvirinae Genus Simplexvirus; type species: Human herpesvirus 1 or Herpes simplex; diseases: cold sores, genital herpes, encephalitis Genus Varicellovirus; type species: Human herpesvirus 3 or Varicella-zoster virus; diseases: chickenpox, shingles Genus Mardivirus; type species: Gallid herpesvirus 2 Genus Iltovirus; type species: Gallid herpesvirus 1 - Genus Simplexvirus; type species: Human herpesvirus 1 or Herpes simplex; diseases: cold sores, genital herpes, encephalitis - Genus Varicellovirus; type species: Human herpesvirus 3 or Varicella-zoster virus; diseases: chickenpox, shingles - Genus Mardivirus; type species: Gallid herpesvirus 2 - Genus Iltovirus; type species: Gallid herpesvirus 1 - Subfamily Betaherpesvirinae Genus Cytomegalovirus; type species: Human herpesvirus 5; diseases: mononucleosis Genus Muromegalovirus; type species: Murid herpesvirus 1 Genus Roseolovirus; type species: Human herpesvirus 6; diseases: erythema subitum, roseola infantum - Genus Cytomegalovirus; type species: Human herpesvirus 5; diseases: mononucleosis - Genus Muromegalovirus; type species: Murid herpesvirus 1 - Genus Roseolovirus; type species: Human herpesvirus 6; diseases: erythema subitum, roseola infantum - Subfamily Gammaherpesvirinae Genus Lymphocryptovirus; type species: Human herpesvirus 4 or Epstein-Barr virus; diseases: mononucleosis, Burkitt's lymphoma, nasopharyngeal carcinoma, Hodgkin's disease Genus Rhadinovirus; type species: Human Herpesvirus 8, Saimiriine herpesvirus 2 - Genus Lymphocryptovirus; type species: Human herpesvirus 4 or Epstein-Barr virus; diseases: mononucleosis, Burkitt's lymphoma, nasopharyngeal carcinoma, Hodgkin's disease - Genus Rhadinovirus; type species: Human Herpesvirus 8, Saimiriine herpesvirus 2 - Unassigned Genus Cercopithecine; type species: Cercopithecine herpesvirus 1 Genus Ictalurivirus; type species: Ictalurid herpesvirus 1 - Genus Cercopithecine; type species: Cercopithecine herpesvirus 1 - Genus Ictalurivirus; type species: Ictalurid herpesvirus 1	Herpesviridae # Overview The Herpesviridae are a large family of DNA viruses that cause diseases in humans and animals.[1] The family name is derived from the Greek word herpein ("to creep"), referring to the latent, re-occurring infections typical of this group of viruses. Herpesviridae can cause latent or lytic infections. # Human herpesviridae There are eight distinct viruses in this family known to cause disease in humans.[2] Monkey B virus (Cercopithecine herpesvirus-1, Herpesvirus simiae) is a simplexvirus endemic in macaque monkeys. Human zoonotic infection typically results in fatal encephalomyelitis or severe neurologic impairment in untreated individuals.[4] ## Viral structure The human herpesviruses all share some common properties. One shared property is virus structure - all herpesviruses are composed of relatively large double-stranded, linear DNA genomes encoding 100-200 genes encased within an icosahedral protein cage called the capsid which is itself wrapped in a lipid bilayer membrane called the envelope. This particle is known as the virion. Following binding of viral envelope glycoproteins to cell membrane receptors, the virion is internalized and dismantled, allowing viral DNA to migrate to the cell nucleus. Within the nucleus, viral DNA limited replication and transcription of viral genes. During symptomatic infection, infected cells transcribe lytic viral genes. In some host cells, a small number of viral genes termed latency associated transcript (LAT) accumulate instead. In this fashion the virus can persist in the cell (and thus the host) indefinitely. Reactivation of latent viruses has been implicated in a number of organic diseases. While primary infection is often accompanied by a self-limited period of clinical illness, long-term latency is symptom-free. Following activation, transcription of viral genes switches from LAT to multiple lytic genes that lead to enhanced replication and virus production. Often, lytic activation leads to cell death. Clinically, lytic activation is often accompanied by emergence of non-specific symptoms such as low grade fever, headache, sore throat, malaise, and rash as well as clinical signs such as swollen or tender lymph nodes and immunological findings such as reduced levels of natural killer cells. # Animal herpesviridae - Subfamily Alphaherpesvirinae Genus Simplexvirus Bovine herpesvirus 2 causes bovine mammillitis and pseudo-lumpyskin disease. Cercopithecine herpesvirus 1, also known as Herpes B virus, causes a Herpes simplex-like disease in Macaques. Ateline herpesvirus 1, Spider monkey herpesvirus. Genus Varicellovirus Bovine herpesvirus 1 causes infectious bovine rhinotracheitis, vaginitis, balanoposthitis, and abortion in cattle. Bovine herpesvirus 5 causes encephalitis in cattle. Caprine herpesvirus 1 causes conjunctivitis and respiratory disease in goats. Porcine herpesvirus 1 causes pseudorabies. Equine herpesvirus 1 causes abortion in horses. Equine herpesvirus 3 causes coital exanthema in horses. Equine herpesvirus 4 causes rhinopneumonitis in horses. Canine herpesvirus 1 causes a severe hemorrhagic disease in puppies. Feline herpesvirus 1 causes feline viral rhinotracheitis and keratitis in cats. Duck herpesvirus 1 causes duck plague. Genus Mardivirus Gallid herpesvirus 2 causes Marek's disease. Gallid herpesvirus 3 (GaHV-3 or MDV-2) Herpesvirus of turkeys (HVT) Genus Iltovirus Gallid herpesvirus 1 causes infectious laryngotracheitis in birds. - Genus Simplexvirus Bovine herpesvirus 2 causes bovine mammillitis and pseudo-lumpyskin disease. Cercopithecine herpesvirus 1, also known as Herpes B virus, causes a Herpes simplex-like disease in Macaques. Ateline herpesvirus 1, Spider monkey herpesvirus. - Bovine herpesvirus 2 causes bovine mammillitis and pseudo-lumpyskin disease. - Cercopithecine herpesvirus 1, also known as Herpes B virus, causes a Herpes simplex-like disease in Macaques. - Ateline herpesvirus 1, Spider monkey herpesvirus. - Genus Varicellovirus Bovine herpesvirus 1 causes infectious bovine rhinotracheitis, vaginitis, balanoposthitis, and abortion in cattle. Bovine herpesvirus 5 causes encephalitis in cattle. Caprine herpesvirus 1 causes conjunctivitis and respiratory disease in goats. Porcine herpesvirus 1 causes pseudorabies. Equine herpesvirus 1 causes abortion in horses. Equine herpesvirus 3 causes coital exanthema in horses. Equine herpesvirus 4 causes rhinopneumonitis in horses. Canine herpesvirus 1 causes a severe hemorrhagic disease in puppies. Feline herpesvirus 1 causes feline viral rhinotracheitis and keratitis in cats. Duck herpesvirus 1 causes duck plague. - Bovine herpesvirus 1 causes infectious bovine rhinotracheitis, vaginitis, balanoposthitis, and abortion in cattle. - Bovine herpesvirus 5 causes encephalitis in cattle. - Caprine herpesvirus 1 causes conjunctivitis and respiratory disease in goats. - Porcine herpesvirus 1 causes pseudorabies. - Equine herpesvirus 1 causes abortion in horses. - Equine herpesvirus 3 causes coital exanthema in horses. - Equine herpesvirus 4 causes rhinopneumonitis in horses. - Canine herpesvirus 1 causes a severe hemorrhagic disease in puppies. - Feline herpesvirus 1 causes feline viral rhinotracheitis and keratitis in cats. - Duck herpesvirus 1 causes duck plague. - Genus Mardivirus Gallid herpesvirus 2 causes Marek's disease. Gallid herpesvirus 3 (GaHV-3 or MDV-2) Herpesvirus of turkeys (HVT) - Gallid herpesvirus 2 causes Marek's disease. - Gallid herpesvirus 3 (GaHV-3 or MDV-2) - Herpesvirus of turkeys (HVT) - Genus Iltovirus Gallid herpesvirus 1 causes infectious laryngotracheitis in birds. - Gallid herpesvirus 1 causes infectious laryngotracheitis in birds. - Subfamily Betaherpesvirinae Porcine herpesvirus 2 causes inclusion body rhinitis in swine. - Porcine herpesvirus 2 causes inclusion body rhinitis in swine. - Subfamily Gammaherpesvirinae Genus Rhadinovirus Alcelaphine herpesvirus 1 causes bovine malignant catarrhal fever. Bovine herpesvirus 4 Equine herpesvirus 2 causes equine cytomegalovirus infection. Equine herpesvirus 5 [5] - Genus Rhadinovirus Alcelaphine herpesvirus 1 causes bovine malignant catarrhal fever. Bovine herpesvirus 4 Equine herpesvirus 2 causes equine cytomegalovirus infection. Equine herpesvirus 5 [5] - Alcelaphine herpesvirus 1 causes bovine malignant catarrhal fever. - Bovine herpesvirus 4 - Equine herpesvirus 2 causes equine cytomegalovirus infection. - Equine herpesvirus 5 [5] # Taxonomy The following genera are included here: - Subfamily Alphaherpesvirinae Genus Simplexvirus; type species: Human herpesvirus 1 or Herpes simplex; diseases: cold sores, genital herpes, encephalitis Genus Varicellovirus; type species: Human herpesvirus 3 or Varicella-zoster virus; diseases: chickenpox, shingles Genus Mardivirus; type species: Gallid herpesvirus 2 Genus Iltovirus; type species: Gallid herpesvirus 1 - Genus Simplexvirus; type species: Human herpesvirus 1 or Herpes simplex; diseases: cold sores, genital herpes, encephalitis - Genus Varicellovirus; type species: Human herpesvirus 3 or Varicella-zoster virus; diseases: chickenpox, shingles - Genus Mardivirus; type species: Gallid herpesvirus 2 - Genus Iltovirus; type species: Gallid herpesvirus 1 - Subfamily Betaherpesvirinae Genus Cytomegalovirus; type species: Human herpesvirus 5; diseases: mononucleosis Genus Muromegalovirus; type species: Murid herpesvirus 1 Genus Roseolovirus; type species: Human herpesvirus 6; diseases: erythema subitum, roseola infantum - Genus Cytomegalovirus; type species: Human herpesvirus 5; diseases: mononucleosis - Genus Muromegalovirus; type species: Murid herpesvirus 1 - Genus Roseolovirus; type species: Human herpesvirus 6; diseases: erythema subitum, roseola infantum - Subfamily Gammaherpesvirinae Genus Lymphocryptovirus; type species: Human herpesvirus 4 or Epstein-Barr virus; diseases: mononucleosis, Burkitt's lymphoma, nasopharyngeal carcinoma, Hodgkin's disease Genus Rhadinovirus; type species: Human Herpesvirus 8, Saimiriine herpesvirus 2 - Genus Lymphocryptovirus; type species: Human herpesvirus 4 or Epstein-Barr virus; diseases: mononucleosis, Burkitt's lymphoma, nasopharyngeal carcinoma, Hodgkin's disease - Genus Rhadinovirus; type species: Human Herpesvirus 8, Saimiriine herpesvirus 2 - Unassigned Genus Cercopithecine; type species: Cercopithecine herpesvirus 1 Genus Ictalurivirus; type species: Ictalurid herpesvirus 1 - Genus Cercopithecine; type species: Cercopithecine herpesvirus 1 - Genus Ictalurivirus; type species: Ictalurid herpesvirus 1	https://www.wikidoc.org/index.php/Herpes_viridae_disease
59a03c9d76b2d394eac71391c5659fad786f8724	wikidoc	Heterochromia	Heterochromia # Overview In anatomy, heterochromia refers to a difference in coloration, usually of the irises but also of hair or skin. Heterochromia (also known as a heterochromia iridis or heterochromia iridium) is an eye condition in which one iris is a different color from the other (complete heterochromia), or where part of one iris is a different color from the remainder (partial heterochromia or sectoral heterochromia). It is a result of the relative excess or lack of pigment within an iris or part of an iris, which may be genetically inherited or due to mosaicism, or acquired by disease or injury. Eye color, specifically the color of the irises, is determined primarily by the concentration and distribution of melanin pigment within the iris tissues. Consequently, anything affecting those factors may result in a difference of color being observed. The affected eye may be hyperpigmented (hyperchromic) or hypopigmented (hypochromic). An excess of pigmentation is usually associated with hyperplasia of the iris tissues whereas a lack of pigmentation is associated with hypoplasia. Although seen in humans, heterochromia in which one iris differs in color from the other iris is more frequently observed in non-human species such as cats (for example, Japanese Bobtails and Turkish Vans; white, shorthaired cats can be "odd-eyed" with one copper or orange eye and one blue eye, and the Turkish Angora), dogs (for example, Siberian Huskies as well as Australian Shepherds, Border Collies, and other breeds with merle coats), horses (so-called "wall-eyed" horses have one brown and one white or blue eye), and even water buffalo. Partial or sectoral heterochromia is much less common than complete heterochromia and is typically found in autosomally inherited disorders such as Hirschsprung's disease and Waardenburg syndrome. Famous comedian Dan Akroyd has this condition. # Classification based on etiology Although a distinction is frequently made between heterochromia that affects an eye completely or only partially, it is often classified as either genetic (due to mosaicism or congenital) or acquired, with mention as to whether the affected iris or portion of the iris is darker or lighter. ## Congenital heterochromia Heterochromia that is congenital is usually inherited as an autosomal dominant trait. - Lisch nodules - iris hamartomas seen in neurofibromatosis. - Ocular melanosis - a condition characterized by increased pigmentation of the uveal tract, episclera, and anterior chamber angle. - Oculodermal melanocytosis (nevus of Ota) - Pigment dispersion syndrome - a condition characterized by loss of pigmentation from the posterior iris surface which is disseminated intraocularly and deposited on various intraocular structures, including the anterior surface of the iris. - Sturge-Weber syndrome - a syndrome characterized by a port-wine stain nevus in the distribution of the trigeminal nerve, homolateral meningeal angioma with intracranial calcification and neurologic signs, and angioma of the choroid, often with secondary glaucoma. - Simple heterochromia - a rare condition characterized by the absence of other ocular or systemic problems. The lighter eye is typically regarded as the affected eye as it usually shows iris hypoplasia. It may affect an iris completely or only partially. - Congenital Horner's syndrome - sometimes inherited, although usually acquired - Waardenburg's syndrome - a syndrome in which heterochromia presents as a bilateral iris hypochromia in some cases. A Japanese review of 11 albino children with the disorder found that all had sectoral/partial heterochromia. - Piebaldism - similar to Waardenburg's syndrome, a rare disorder of melanocyte development characterized by a white forelock and multiple symmetrical hypopigmented or depigmented macules. - Hirschsprung's disease - a bowel disorder associated with heterochromia in the form of a sector hypochromia. The affected sectors have been shown to have reduced numbers of melanocytes and decreased stromal pigmentation. - Incontinentia pigmenti - Parry-Romberg syndrome ## Acquired heterochromia Heterochromia that is acquired is usually due to injury, inflammation, the use of certain eyedrops, or tumors. - Deposition of material Siderosis - iron deposition within ocular tissues due to a penetrating injury and a retained iron-containing, intraocular foreign body. Hemosiderosis - long standing hyphema (blood in the anterior chamber) following blunt trauma to the eye may lead to iron deposition from blood products - Siderosis - iron deposition within ocular tissues due to a penetrating injury and a retained iron-containing, intraocular foreign body. - Hemosiderosis - long standing hyphema (blood in the anterior chamber) following blunt trauma to the eye may lead to iron deposition from blood products - Use of certain eyedrops - prostaglandin analogues (latanoprost, isopropyl unoprostone, travoprost, and bimatoprost) are used topically to lower intraocular pressure in glaucoma patients. A concentric heterochromia has developed in some patients applying these drugs. The stroma around the iris sphincter muscle becomes darker than the peripheral stroma. A stimulation of melanin synthesis within iris melanocytes has been postulated. - Neoplasm - Nevi and melanomatous tumors. - Iridocorneal endothelium syndrome - Iris ectropion syndrome - Fuchs' heterochromic iridocyclitis - a condition characterized by a low grade, asymptomatic uveitis in which the iris in the affected eye becomes hypochromic and has a washed-out, somewhat moth eaten appearance. The heterochromia can be very subtle, especially in patients with lighter colored irises. It is often most easily seen in daylight. The prevalence of heterochromia associated with Fuch's has been estimated in various studies with results suggesting that there is more difficulty recognizing iris color changes in dark-eyed individuals. - Acquired Horner's syndrome - usually acquired, as in neuroblastoma, although sometimes inherited. - Neoplasm - Melanomas can also be very lightly pigmented, and a lighter colored iris may be a rare manifestation of metastatic disease to the eye. Heterochromia has also been observed in those with Duane syndrome. - Chronic iritis - Juvenile xanthogranuloma - Leukemia and lymphoma # Causes ## Life Threatening Causes - Leukemia - Lymphoma - Neoplasm ## Common Causes - Acquired horner's syndrome - Chronic iritis - Congenital horner's syndrome - Duane syndrome - Eye hemorrhage - Eye injury - Foreign body in eye - Glaucoma - Hypoplasia - Incontinentia pigmenti - Iridocorneal endothelium syndrome - Iris ectropion syndrome - Pigment dispersion syndrome - Rubeosis iridis - Uveitis ## Causes by Organ System ## Causes in Alphabetical Order - Acquired horner's syndrome - Bimatoprost - Chromosome 8 trisomy syndrome - Chronic iritis - Congenital horner's syndrome - Duane syndrome - Eye hemorrhage - Eye injury - Foreign body in eye - Fuchs' heterochromic cyclitis - Fuch's heterochromic iridis - Fuchs' heterochromic iridocyclitis - Glaucoma - Hemosiderosis - Hirschsprung's disease - Hypoplasia - Incontinentia pigmenti - Inherited trait - Iridocorneal endothelium syndrome - Iris ectropion syndrome - Isopropyl unoprostone - Juvenile xanthogranuloma - Latanoprost - Leukemia - Lisch nodules - Lymphoma - Neoplasm - Neurofibromatosis - Ocular melanosis - Parry-romberg syndrome - Piebaldism - Pigment dispersion syndrome - Rubeosis iridis - Siderosis - Sturge-weber syndrome - Travoprost - Uveitis - Waardenburg's syndrome	Heterochromia Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Luke Rusowicz-Orazem, B.S. # Overview In anatomy, heterochromia refers to a difference in coloration, usually of the irises but also of hair or skin. Heterochromia (also known as a heterochromia iridis or heterochromia iridium) is an eye condition in which one iris is a different color from the other (complete heterochromia), or where part of one iris is a different color from the remainder (partial heterochromia or sectoral heterochromia). It is a result of the relative excess or lack of pigment within an iris or part of an iris, which may be genetically inherited or due to mosaicism, or acquired by disease or injury.[1] Eye color, specifically the color of the irises, is determined primarily by the concentration and distribution of melanin pigment within the iris tissues[2][3][4]. Consequently, anything affecting those factors may result in a difference of color being observed. The affected eye may be hyperpigmented (hyperchromic) or hypopigmented (hypochromic).[5] An excess of pigmentation is usually associated with hyperplasia of the iris tissues whereas a lack of pigmentation is associated with hypoplasia. Although seen in humans, heterochromia in which one iris differs in color from the other iris is more frequently observed in non-human species such as cats (for example, Japanese Bobtails and Turkish Vans; white, shorthaired cats can be "odd-eyed" with one copper or orange eye and one blue eye, and the Turkish Angora), dogs (for example, Siberian Huskies as well as Australian Shepherds, Border Collies, and other breeds with merle coats), horses (so-called "wall-eyed" horses have one brown and one white or blue eye), and even water buffalo.[6] Partial or sectoral heterochromia is much less common than complete heterochromia and is typically found in autosomally inherited disorders such as Hirschsprung's disease and Waardenburg syndrome. Famous comedian Dan Akroyd has this condition. # Classification based on etiology Although a distinction is frequently made between heterochromia that affects an eye completely or only partially, it is often classified as either genetic (due to mosaicism or congenital) or acquired, with mention as to whether the affected iris or portion of the iris is darker or lighter.[7] ## Congenital heterochromia Heterochromia that is congenital is usually inherited as an autosomal dominant trait. - Lisch nodules - iris hamartomas seen in neurofibromatosis. - Ocular melanosis - a condition characterized by increased pigmentation of the uveal tract, episclera, and anterior chamber angle. - Oculodermal melanocytosis (nevus of Ota)[5] - Pigment dispersion syndrome - a condition characterized by loss of pigmentation from the posterior iris surface which is disseminated intraocularly and deposited on various intraocular structures, including the anterior surface of the iris. - Sturge-Weber syndrome - a syndrome characterized by a port-wine stain nevus in the distribution of the trigeminal nerve, homolateral meningeal angioma with intracranial calcification and neurologic signs, and angioma of the choroid, often with secondary glaucoma[8][2]. - Simple heterochromia - a rare condition characterized by the absence of other ocular or systemic problems. The lighter eye is typically regarded as the affected eye as it usually shows iris hypoplasia. It may affect an iris completely or only partially. - Congenital Horner's syndrome[9] - sometimes inherited, although usually acquired - Waardenburg's syndrome[9] - a syndrome in which heterochromia presents as a bilateral iris hypochromia in some cases. A Japanese review of 11 albino children with the disorder found that all had sectoral/partial heterochromia.[10] - Piebaldism - similar to Waardenburg's syndrome, a rare disorder of melanocyte development characterized by a white forelock and multiple symmetrical hypopigmented or depigmented macules. - Hirschsprung's disease - a bowel disorder associated with heterochromia in the form of a sector hypochromia. The affected sectors have been shown to have reduced numbers of melanocytes and decreased stromal pigmentation.[11] - Incontinentia pigmenti[5] - Parry-Romberg syndrome[5] ## Acquired heterochromia Heterochromia that is acquired is usually due to injury, inflammation, the use of certain eyedrops, or tumors. - Deposition of material Siderosis - iron deposition within ocular tissues due to a penetrating injury and a retained iron-containing, intraocular foreign body. Hemosiderosis - long standing hyphema (blood in the anterior chamber) following blunt trauma to the eye may lead to iron deposition from blood products - Siderosis - iron deposition within ocular tissues due to a penetrating injury and a retained iron-containing, intraocular foreign body. - Hemosiderosis - long standing hyphema (blood in the anterior chamber) following blunt trauma to the eye may lead to iron deposition from blood products - Use of certain eyedrops - prostaglandin analogues (latanoprost, isopropyl unoprostone, travoprost, and bimatoprost) are used topically to lower intraocular pressure in glaucoma patients. A concentric heterochromia has developed in some patients applying these drugs. The stroma around the iris sphincter muscle becomes darker than the peripheral stroma. A stimulation of melanin synthesis within iris melanocytes has been postulated. - Neoplasm - Nevi and melanomatous tumors. - Iridocorneal endothelium syndrome[5] - Iris ectropion syndrome[5] - Fuchs' heterochromic iridocyclitis - a condition characterized by a low grade, asymptomatic uveitis in which the iris in the affected eye becomes hypochromic and has a washed-out, somewhat moth eaten appearance. The heterochromia can be very subtle, especially in patients with lighter colored irises. It is often most easily seen in daylight. The prevalence of heterochromia associated with Fuch's has been estimated in various studies[12][13][14] with results suggesting that there is more difficulty recognizing iris color changes in dark-eyed individuals.[14][15] - Acquired Horner's syndrome - usually acquired, as in neuroblastoma,[16] although sometimes inherited. - Neoplasm - Melanomas can also be very lightly pigmented, and a lighter colored iris may be a rare manifestation of metastatic disease to the eye. Heterochromia has also been observed in those with Duane syndrome.[17][18] - Chronic iritis[5] - Juvenile xanthogranuloma[5] - Leukemia and lymphoma[5] # Causes ## Life Threatening Causes - Leukemia - Lymphoma - Neoplasm ## Common Causes - Acquired horner's syndrome - Chronic iritis - Congenital horner's syndrome - Duane syndrome - Eye hemorrhage - Eye injury - Foreign body in eye - Glaucoma - Hypoplasia - Incontinentia pigmenti - Iridocorneal endothelium syndrome - Iris ectropion syndrome - Pigment dispersion syndrome - Rubeosis iridis - Uveitis ## Causes by Organ System ## Causes in Alphabetical Order - Acquired horner's syndrome - Bimatoprost - Chromosome 8 trisomy syndrome - Chronic iritis - Congenital horner's syndrome - Duane syndrome - Eye hemorrhage - Eye injury - Foreign body in eye - Fuchs' heterochromic cyclitis - Fuch's heterochromic iridis - Fuchs' heterochromic iridocyclitis - Glaucoma - Hemosiderosis - Hirschsprung's disease - Hypoplasia - Incontinentia pigmenti - Inherited trait - Iridocorneal endothelium syndrome - Iris ectropion syndrome - Isopropyl unoprostone - Juvenile xanthogranuloma - Latanoprost - Leukemia - Lisch nodules - Lymphoma - Neoplasm - Neurofibromatosis - Ocular melanosis - Parry-romberg syndrome - Piebaldism - Pigment dispersion syndrome - Rubeosis iridis - Siderosis - Sturge-weber syndrome - Travoprost - Uveitis - Waardenburg's syndrome	https://www.wikidoc.org/index.php/Heterochromia
4a9c3e9fb7d94636244dd7fdc0391341b609eca3	wikidoc	Heterogeneous	Heterogeneous Heterogeneous means that something (an object or system) consists of a diverse range of opposite items. It is the antonym of homogeneous, which means that an object or system consists of many identical items. Matters of a quantum can exist in homogenous or in heterogeneous or in combined distributions. The term is often used in a scientific (such as a kind of catalyst), mathematical, sociological or statistical context. A heterogeneous compound, mixture, reaction or other such object is one that consists of many different items, which are often not easily sorted or separated, though they are clearly distinct. A heterogeneous mixture is a mixture of two or more compounds. In chemical kinetics, a heterogeneous reaction is one that takes place at the interface of two or more i.e. between a solid and a gas, a liquid and a gas, or a solid and a liquid. - amorphous - heterozygous - heteroazeotrope - homogenization - homozygous - mesoporous silicates # Statistics In meta analysis the term refers to the presence of multiple non-random intercepts in a dataset. In Meta-analysis of clinical studies which involves comparing and quantifying the effects of separate studies, heterogeneity refers to the differences in study populations or in methodologies used to study them that may have the effect of reaching differing conclusions. This is a problem as it calls into question conclusions that are drawn from studies and reduces their comparability. The following concepts are important in understanding the importance of heterogeneity in meta-analytical research. Clinical Heterogeneity: Heterogeneity resulting from differences in clinical features of a population that is being studied or treated. Methodological Heterogeneity: Heterogeneity resulting from the differential use of study methodology. These may lead to different conclusions in different studies, despite their clinical characteristics being the same. Statistical Heterogeneity: Heterogeneity resulting from either clinical or statistical heterogeneity, which leads to a difference in expected results, more than which can be accounted for by chance. # Systems In the world of enterprise computing, heterogeneous data is a mix of data from two or more sources, often of two or more formats, e.g., SQL and XML. Distributed systems are called heterogeneous if they contain many different types of hardware and software.	Heterogeneous Heterogeneous means that something (an object or system) consists of a diverse range of opposite items. It is the antonym of homogeneous, which means that an object or system consists of many identical items. Matters of a quantum can exist in homogenous or in heterogeneous or in combined distributions. The term is often used in a scientific (such as a kind of catalyst), mathematical, sociological or statistical context. A heterogeneous compound, mixture, reaction or other such object is one that consists of many different items, which are often not easily sorted or separated, though they are clearly distinct. A heterogeneous mixture is a mixture of two or more compounds. In chemical kinetics, a heterogeneous reaction is one that takes place at the interface of two or more i.e. between a solid and a gas, a liquid and a gas, or a solid and a liquid. - amorphous - heterozygous - heteroazeotrope - homogenization - homozygous - mesoporous silicates # Statistics In meta analysis the term refers to the presence of multiple non-random intercepts in a dataset. In Meta-analysis of clinical studies which involves comparing and quantifying the effects of separate studies, heterogeneity refers to the differences in study populations or in methodologies used to study them that may have the effect of reaching differing conclusions. This is a problem as it calls into question conclusions that are drawn from studies and reduces their comparability. The following concepts are important in understanding the importance of heterogeneity in meta-analytical research. Clinical Heterogeneity: Heterogeneity resulting from differences in clinical features of a population that is being studied or treated. Methodological Heterogeneity: Heterogeneity resulting from the differential use of study methodology. These may lead to different conclusions in different studies, despite their clinical characteristics being the same. Statistical Heterogeneity: Heterogeneity resulting from either clinical or statistical heterogeneity, which leads to a difference in expected results, more than which can be accounted for by chance. # Systems In the world of enterprise computing, heterogeneous data is a mix of data from two or more sources, often of two or more formats, e.g., SQL and XML. Distributed systems are called heterogeneous if they contain many different types of hardware and software.	https://www.wikidoc.org/index.php/Heterogeneity
58cf3a69da2870979e00ecf3b3e149a7d13d1437	wikidoc	Palmitic acid	Palmitic acid Palmitic acid, or hexadecanoic acid in IUPAC nomenclature, is one of the most common saturated fatty acids found in animals and plants. As its name indicates, it is a major component of the oil from palm trees (palm oil and palm kernel oil). The word palmitic is from the French "palmitique", the pith of the palm tree. Butter, cheese, milk and meat also contain this fatty acid. Palmitate is a term for the salts or esters of palmitic acid. The palmitate anion is the observed form of palmitic acid at physiological pH. # Biochemistry Palmitic acid is the first fatty acid produced during lipogenesis (fatty acid synthesis) and from which longer fatty acids can be produced. Palmitate negatively feeds back on acetyl-CoA carboxylase (ACC) which is responsible for converting acetyl-ACP to malonyl-ACP on the growing acyl chain, thus preventing further palmitate generation. Reduction of palmitic acid yields cetyl alcohol. # Uses Palmitate is an antioxidant and a vitamin A compound added to low fat milk to replace the vitamin content lost through the removal of milk fat. Palmitate is attached to the alcohol form of vitamin A, retinol, in order to make vitamin A stable in milk. Derivatives of palmitic acid were used in combination with naphtha during World War II to produce napalm (naphthenic and palmitic acids). The WHO reports "convincing" evidence that dietary intake of palmitic acid increases risk of developing cardiovascular diseases. However, possibly less-disinterested studies have shown no ill effect, or even a favorable effect, of dietary consumption of palmitic acid on blood lipids and cardiovascular disease, so that the WHO finding may be deemed controversial. The controversy may be resolved by a study showing palmitic acid to have no hypercholesterolaemic effect if intake of linoleic acid was greater than 4.5% of energy, but that if the diet contained trans fatty acids, the health effects would be unfavorable (with an LDL cholesterol increase and HDL cholesterol decrease).	Palmitic acid Template:Chembox new Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Palmitic acid, or hexadecanoic acid in IUPAC nomenclature, is one of the most common saturated fatty acids found in animals and plants. As its name indicates, it is a major component of the oil from palm trees (palm oil and palm kernel oil). The word palmitic is from the French "palmitique", the pith of the palm tree. Butter, cheese, milk and meat also contain this fatty acid. Palmitate is a term for the salts or esters of palmitic acid. The palmitate anion is the observed form of palmitic acid at physiological pH.[citation needed] # Biochemistry Palmitic acid is the first fatty acid produced during lipogenesis (fatty acid synthesis) and from which longer fatty acids can be produced. Palmitate negatively feeds back on acetyl-CoA carboxylase (ACC) which is responsible for converting acetyl-ACP to malonyl-ACP on the growing acyl chain, thus preventing further palmitate generation.[citation needed] Reduction of palmitic acid yields cetyl alcohol.[citation needed] # Uses Palmitate is an antioxidant and a vitamin A compound added to low fat milk to replace the vitamin content lost through the removal of milk fat. Palmitate is attached to the alcohol form of vitamin A, retinol, in order to make vitamin A stable in milk. Derivatives of palmitic acid were used in combination with naphtha during World War II to produce napalm (naphthenic and palmitic acids). The WHO reports "convincing" evidence that dietary intake of palmitic acid increases risk of developing cardiovascular diseases. [1] However, possibly less-disinterested studies have shown no ill effect, or even a favorable effect, of dietary consumption of palmitic acid on blood lipids and cardiovascular disease, so that the WHO finding may be deemed controversial.[2] The controversy may be resolved by a study showing palmitic acid to have no hypercholesterolaemic effect if intake of linoleic acid was greater than 4.5% of energy, but that if the diet contained trans fatty acids, the health effects would be unfavorable (with an LDL cholesterol increase and HDL cholesterol decrease). [3]	https://www.wikidoc.org/index.php/Hexadecanoic_acid
7e4e0f303936b7dda5c75eab2c96719cf12a23ce	wikidoc	Hoechst stain	Hoechst stain The Hoechst stains are part of a family of fluorescent stains for labelling DNA in fluorescence microscopy. Because these fluorescent stains label DNA, they are also commonly used to visualize nuclei and mitochondria. Two of these closely related bis-benzimides are commonly used: Hoechst 33258 and Hoechst 33342. Both dyes are excited by ultraviolet light at around 350 nm, and both emit blue/cyan fluorescence light around an emission maximum at 461 nm. The Hoechst stains may be used on live or fixed cells, and are often used as a substitute for another nucleic acid stain, DAPI. The key difference between them is that the additional ethyl group of Hoechst 33342 renders it more lipophilic, and thus more able to cross intact cell membranes. In some applications, Hoechst 33258 is significantly less permeant. These dyes can also be used to detect the contents of a sample DNA by plotting a standard emission-to-content curve. Because the Hoechst stains bind to DNA, they can disrupt DNA replication during cell division. Consequently they are potentially mutagenic and carcinogenic. Care should be taken in their handling and disposal.	Hoechst stain The Hoechst stains are part of a family of fluorescent stains for labelling DNA in fluorescence microscopy. Because these fluorescent stains label DNA, they are also commonly used to visualize nuclei and mitochondria. Two of these closely related bis-benzimides are commonly used: Hoechst 33258 and Hoechst 33342. Both dyes are excited by ultraviolet light at around 350 nm, and both emit blue/cyan fluorescence light around an emission maximum at 461 nm. The Hoechst stains may be used on live or fixed cells, and are often used as a substitute for another nucleic acid stain, DAPI. The key difference between them is that the additional ethyl group of Hoechst 33342 renders it more lipophilic, and thus more able to cross intact cell membranes. In some applications, Hoechst 33258 is significantly less permeant. These dyes can also be used to detect the contents of a sample DNA by plotting a standard emission-to-content curve. Because the Hoechst stains bind to DNA, they can disrupt DNA replication during cell division. Consequently they are potentially mutagenic and carcinogenic. Care should be taken in their handling and disposal. Template:WH Template:WikiDoc Sources	https://www.wikidoc.org/index.php/Hoechst_stain
69bd15613c58d1c1ecd55cd0641d0075baa3c45a	wikidoc	Homo ergaster	Homo ergaster Homo ergaster ("working man") is an extinct hominid species (or subspecies, according to some authorities) which lived throughout eastern and southern Africa between 1.9 to 1.4 million years ago with the advent of the lower Pleistocene and the cooling of the global climate. H. ergaster is sometimes categorized as a subspecies of Homo erectus. It is currently somewhat controversial whether H. ergaster or the later, Asian H. erectus was the direct ancestor of modern humans. The genetic variability among modern Homo sapiens is greatest in Africa, which suggests strongly that this is the area where the species arose and has had most time to accumulate variation. H. ergaster may be distinguished from H. erectus by its thinner skull bones and lack of an obvious sulcus. Derived features include reduced sexual dimorphism; a smaller, more orthognathic face; a smaller dental arcade; and a larger (700 and 850cc) cranial capacity. It is estimated that H. ergaster stood at 1.9m (6ft3) tall with relatively less sexual dimorphism in comparison to earlier hominins. Remains have been found in Tanzania, Ethiopia, Kenya, and South Africa. The most complete Homo ergaster skeleton ever discovered was made at Lake Turkana, Kenya in 1984. Paleanthropologists Richard Leakey, Kamoya Kimeu and Tim White dubbed the 1.6 million year old specimen as KNM-WT 15000 (nicknamed "Turkana Boy"). The type specimen of H. ergaster is KNM ER 992; the species was named by Groves and Mazak in 1975. The species name originates from the Greek ergaster meaning "Workman". This name was chosen due to the discovery of various tools such as hand-axes and cleavers near the skeletal remains of H. ergaster. This is one of the reasons that it is sometimes set apart distinctly from other human ancestors. Its use of advanced (rather than simple) tools was unique to this species; H. ergaster tool use belongs to the Acheulean industry. H. ergaster first began using these tools 1.6 million years ago. Charred animal bones in fossil deposits and traces of camps suggest that the species made creative use of fire. # Notable fossils - KNM ER 3733 - Turkana boy - also classified as Homo erectus - KNM ER 992	Homo ergaster Homo ergaster ("working man") is an extinct hominid species (or subspecies, according to some authorities) which lived throughout eastern and southern Africa between 1.9 to 1.4 million years ago with the advent of the lower Pleistocene and the cooling of the global climate. H. ergaster is sometimes categorized as a subspecies of Homo erectus. It is currently somewhat controversial whether H. ergaster or the later, Asian H. erectus was the direct ancestor of modern humans. The genetic variability among modern Homo sapiens is greatest in Africa, which suggests strongly that this is the area where the species arose and has had most time to accumulate variation. H. ergaster may be distinguished from H. erectus by its thinner skull bones and lack of an obvious sulcus. Derived features include reduced sexual dimorphism; a smaller, more orthognathic face; a smaller dental arcade; and a larger (700 and 850cc) cranial capacity. It is estimated that H. ergaster stood at 1.9m (6ft3) tall with relatively less sexual dimorphism in comparison to earlier hominins. Remains have been found in Tanzania, Ethiopia, Kenya, and South Africa. The most complete Homo ergaster skeleton ever discovered was made at Lake Turkana, Kenya in 1984. Paleanthropologists Richard Leakey, Kamoya Kimeu and Tim White dubbed the 1.6 million year old specimen as KNM-WT 15000 (nicknamed "Turkana Boy"). The type specimen of H. ergaster is KNM ER 992[1]; the species was named by Groves and Mazak in 1975. The species name originates from the Greek ergaster meaning "Workman". This name was chosen due to the discovery of various tools such as hand-axes and cleavers near the skeletal remains of H. ergaster. This is one of the reasons that it is sometimes set apart distinctly from other human ancestors. Its use of advanced (rather than simple) tools was unique to this species; H. ergaster tool use belongs to the Acheulean industry. H. ergaster first began using these tools 1.6 million years ago. Charred animal bones in fossil deposits and traces of camps suggest that the species made creative use of fire. # Notable fossils - KNM ER 3733 - Turkana boy - also classified as Homo erectus - KNM ER 992	https://www.wikidoc.org/index.php/Homo_ergaster
509c16ff2639d3a5ede51a7a15abcb3dc0af01b5	wikidoc	Homochirality	Homochirality Homochirality is a term used to refer to a group of molecules that possess the same sense of chirality. Molecules involved are not necessarily the same compound, but similar groups are arranged in the same way around a central atom. In biology homochirality is found inside living organisms. Active forms of amino acids are all of the L-form and most biologically relevant sugars are of the D-form. Typically, the alternative form is inactive and sometimes even toxic to living things. The origin of this phenomenon is not clearly understood. It is even unclear if homochirality has a purpose. One suggestion is that it reduces entropy barriers in the formation of large organized molecules. It has been experimentally verified that amino acids form large aggregates in larger abundance from enantiopure substrates than from racemic ones. . Homochirality is said to evolve in three distinct steps: mirror-symmetry breaking creates a minute enantiomeric imbalance and is key to homochirality, chiral amplification is a process of enantiomeric enrichment and chiral transmission allows the transfer of chirality of one set of molecules to another. # Mirror-symmetry breaking Explaining how an enantiomeric imbalance is created is the first place is the most difficult question to answer. Supporters exist for an extraterrestrial origin based on findings relating to the Murchison meteorite. There is evidence for the existence of circularly polarized light in space (originating from white dwarfs) which may trigger the formation of optical isomers. One classic study involves an experiment that takes place in the laboratory. When sodium chlorate is allowed to crystallize from water and the collected crystals examined in a polarimeter, each crystal turns out to be chiral and either the L form or the D form. In an ordinary experiment the amount of L crystals collected equals the amount of D crystals (corrected for statistical effects). However when the sodium chlorate solution is stirred during the crystallization process the crystals are either exclusively L or exclusively D. In 32 consecutive crystallization experiments 14 experiments deliver D-crystals and 18 others L-crystals. The explanation for this symmetry breaking is unclear but is related to autocatalysis taking place in the nucleation process. # Chiral amplification Laboratory experiments exist demonstrating how in certain autocatalytic reaction systems the presence of a small amount of reaction product with enantiomeric excess at the start of the reaction can result in a much larger enantiomeric excess at the end of the reaction. In one pioneering study, pyrimidine-5-carbaldehyde (Scheme 1) is alkylated by diisopropylzinc to the corresponding pyrimidyl alcohol. Because the initial reaction product is also an effective catalyst the reaction is autocatalytic. The presence of just 0.2 equivalent of the alcohol S-enantiomer at the start of the reaction is sufficient to amplify the enantiomeric excess to 93%. Another study concerns the proline catalyzed aminoxylation of propionaldehyde by nitrosobenzene (scheme 2). In this system too the presence of enantioenriched catalyst drives the reaction towards one of the two possible optical isomers. Serine octamer clusters are also contenders. These clusters of 8 serine molecules appear in mass spectroscopy with an unusual homochiral preference, however there is no evidence that such clusters exist under non-ionizing conditions and amino acid phase behavior is far more prebiotically relevant . The recent observation that partial sublimation of a 10% enantioenriched sample of leucine results in up to 82% enrichment in the sublimate shows that enantioenrichment of amino acids could occur in space . Partial sublimation processes can take place on the surface of meteors where large variations in temperature exist. This finding may have consequences for the development of the Mars Organic Detector scheduled for lauch in 2013 which aims to recover trace amounts of amino acids from the Mars surface exactly by a sublimation technique. A high asymmetric amplification of the enantiomeric excess of sugars are also present in the amino acid catalyzed asymmetric formation of carbohydrates # Chiral transmission Many strategies in asymmetric synthesis are built on chiral transmission. Especially important is the so-called organocatalysis of organic reactions by proline for example in Mannich reactions. # Optical resolution in racemic amino acids There exists no theory elucidating correlations among L-amino acids. If one takes, for example, alanine, which has a small methyl group, and phenylalanine, which has a big benzyl group, a simple question is in what aspect, L-alanine resembles L-phenylalanine more than D-phenylalanine, and what kind of mechanism causes the selection of all L-amino acids. Because it might be possible that alanine was L and phenylalanine was D. It was reported in 2004 that excess racemic D,L-asparagine (Asn), which spontaneously forms crystals of either isomer during recrystallization, induces asymmetric resolution of a co-existing racemic amino acid such as arginine (Arg), aspartic acid (Asp), glutamine (Gln), histidine (His), leucine (Leu), methionine (Met), phenylalanine (Phe), serine (Ser), valine (Val), tyrosine (Tyr), and tryptophan (Trp). The enantiomeric excess {ee=100x(L-D)/(L+D)} of these amino acids was correlated almost linearly with that of the inducer, i.e., Asn. When recrystallizations from a mixture of 12 D,L-amino acids (Ala, Asp, Arg, Glu, Gln, His, Leu, Met, Ser, Val, Phe, and Tyr) and excess D,L-Asn were made, all amino acids with the same configuration with Asn were preferentially co-crystallized. It was incidental whether the enrichment took place in L- or D-Asn, however, once the selection was made, the co-existing amino acid with the same configuration at the α-carbon was preferentially involved because of thermodynamic stability in the crystal formation. The maximal ee was reported to be 100%. Based on these results, it is proposed that a mixture of racemic amino acids causes spontaneous and effective optical resolution, even if asymmetric synthesis of a single amino acid does not occur without an aid of an optically active molecule. This is the first study elucidating reasonably the formation of chirality from racemic amino acids with experimental evidences. # History This term was introduced by Kelvin in 1904, the year that published his Baltimore Lecture of 1884. Recently, however, homochiral has been used in the same sense as enantiomerically pure. This is permitted in some journals (but not encouraged), its meaning changing into the preference of a process or system for a single optical isomer in a pair of isomers in these journals.	Homochirality Homochirality is a term used to refer to a group of molecules that possess the same sense of chirality. Molecules involved are not necessarily the same compound, but similar groups are arranged in the same way around a central atom. In biology homochirality is found inside living organisms. Active forms of amino acids are all of the L-form and most biologically relevant sugars are of the D-form. Typically, the alternative form is inactive and sometimes even toxic to living things. The origin of this phenomenon is not clearly understood. It is even unclear if homochirality has a purpose. One suggestion is that it reduces entropy barriers in the formation of large organized molecules. It has been experimentally verified that amino acids form large aggregates in larger abundance from enantiopure substrates than from racemic ones. [1]. Homochirality is said to evolve in three distinct steps: mirror-symmetry breaking creates a minute enantiomeric imbalance and is key to homochirality, chiral amplification is a process of enantiomeric enrichment and chiral transmission allows the transfer of chirality of one set of molecules to another. # Mirror-symmetry breaking Explaining how an enantiomeric imbalance is created is the first place is the most difficult question to answer. Supporters exist for an extraterrestrial origin based on findings relating to the Murchison meteorite. There is evidence for the existence of circularly polarized light in space (originating from white dwarfs) which may trigger the formation of optical isomers. One classic study involves an experiment that takes place in the laboratory.[2] When sodium chlorate is allowed to crystallize from water and the collected crystals examined in a polarimeter, each crystal turns out to be chiral and either the L form or the D form. In an ordinary experiment the amount of L crystals collected equals the amount of D crystals (corrected for statistical effects). However when the sodium chlorate solution is stirred during the crystallization process the crystals are either exclusively L or exclusively D. In 32 consecutive crystallization experiments 14 experiments deliver D-crystals and 18 others L-crystals. The explanation for this symmetry breaking is unclear but is related to autocatalysis taking place in the nucleation process. # Chiral amplification Laboratory experiments exist demonstrating how in certain autocatalytic reaction systems the presence of a small amount of reaction product with enantiomeric excess at the start of the reaction can result in a much larger enantiomeric excess at the end of the reaction. In one pioneering study,[3] pyrimidine-5-carbaldehyde (Scheme 1) is alkylated by diisopropylzinc to the corresponding pyrimidyl alcohol. Because the initial reaction product is also an effective catalyst the reaction is autocatalytic. The presence of just 0.2 equivalent of the alcohol S-enantiomer at the start of the reaction is sufficient to amplify the enantiomeric excess to 93%. Another study [4] concerns the proline catalyzed aminoxylation of propionaldehyde by nitrosobenzene (scheme 2). In this system too the presence of enantioenriched catalyst drives the reaction towards one of the two possible optical isomers. Serine octamer clusters [5][6] are also contenders. These clusters of 8 serine molecules appear in mass spectroscopy with an unusual homochiral preference, however there is no evidence that such clusters exist under non-ionizing conditions and amino acid phase behavior is far more prebiotically relevant [7]. The recent observation that partial sublimation of a 10% enantioenriched sample of leucine results in up to 82% enrichment in the sublimate shows that enantioenrichment of amino acids could occur in space [8]. Partial sublimation processes can take place on the surface of meteors where large variations in temperature exist. This finding may have consequences for the development of the Mars Organic Detector scheduled for lauch in 2013 which aims to recover trace amounts of amino acids from the Mars surface exactly by a sublimation technique. A high asymmetric amplification of the enantiomeric excess of sugars are also present in the amino acid catalyzed asymmetric formation of carbohydrates[9] # Chiral transmission Many strategies in asymmetric synthesis are built on chiral transmission. Especially important is the so-called organocatalysis of organic reactions by proline for example in Mannich reactions. # Optical resolution in racemic amino acids There exists no theory elucidating correlations among L-amino acids. If one takes, for example, alanine, which has a small methyl group, and phenylalanine, which has a big benzyl group, a simple question is in what aspect, L-alanine resembles L-phenylalanine more than D-phenylalanine, and what kind of mechanism causes the selection of all L-amino acids. Because it might be possible that alanine was L and phenylalanine was D. It was reported[10] in 2004 that excess racemic D,L-asparagine (Asn), which spontaneously forms crystals of either isomer during recrystallization, induces asymmetric resolution of a co-existing racemic amino acid such as arginine (Arg), aspartic acid (Asp), glutamine (Gln), histidine (His), leucine (Leu), methionine (Met), phenylalanine (Phe), serine (Ser), valine (Val), tyrosine (Tyr), and tryptophan (Trp). The enantiomeric excess {ee=100x(L-D)/(L+D)} of these amino acids was correlated almost linearly with that of the inducer, i.e., Asn. When recrystallizations from a mixture of 12 D,L-amino acids (Ala, Asp, Arg, Glu, Gln, His, Leu, Met, Ser, Val, Phe, and Tyr) and excess D,L-Asn were made, all amino acids with the same configuration with Asn were preferentially co-crystallized.[10] It was incidental whether the enrichment took place in L- or D-Asn, however, once the selection was made, the co-existing amino acid with the same configuration at the α-carbon was preferentially involved because of thermodynamic stability in the crystal formation. The maximal ee was reported to be 100%. Based on these results, it is proposed that a mixture of racemic amino acids causes spontaneous and effective optical resolution, even if asymmetric synthesis of a single amino acid does not occur without an aid of an optically active molecule. This is the first study elucidating reasonably the formation of chirality from racemic amino acids with experimental evidences. # History This term was introduced by Kelvin in 1904, the year that published his Baltimore Lecture of 1884.[11][9] Recently, however, homochiral has been used in the same sense as enantiomerically pure. This is permitted in some journals (but not encouraged), its meaning changing into the preference of a process or system for a single optical isomer in a pair of isomers in these journals.	https://www.wikidoc.org/index.php/Homochirality
001432da8b74369883382dad2a2f2616229e72cf	wikidoc	Hoover's sign	Hoover's sign Hoover’s sign is a maneuver aimed to separate organic from non-organic paresis of the leg. The sign relies on the principle of synergistic contraction. Involuntary extension of the "paralized" leg occurs when flexing the contralateral leg against resistance. It has been neglected, although it is a useful clinical test. Essentially, you hold your hand under the contralateral heel and ask the patient to extend the leg off the bed. If you feel pressure from the contralateral heel, the weakness is likely organic. If no pressure is felt, the patient is likely suffering from non-organic limb weakness. Charles Franklin Hoover (1865–1927) was an American physician born in Cleveland, Ohio, who read medicine at Harvard. He worked in Vienna under Neusser, and in Strasburg with F Kraus before returning to Cleveland. He was appointed Professor of Medicine in 1907. His main interests were in diseases of the diaphragm, lungs, and liver. Another Hoover’s sign is inward movement of the lower rib cage during inspiration, implying a flat, but functioning, diaphragm, often associated with COPD	Hoover's sign Template:Search infobox Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Hoover’s sign is a maneuver aimed to separate organic from non-organic paresis of the leg. The sign relies on the principle of synergistic contraction. Involuntary extension of the "paralized" leg occurs when flexing the contralateral leg against resistance. It has been neglected, although it is a useful clinical test. Essentially, you hold your hand under the contralateral heel and ask the patient to extend the leg off the bed. If you feel pressure from the contralateral heel, the weakness is likely organic. If no pressure is felt, the patient is likely suffering from non-organic limb weakness. Charles Franklin Hoover (1865–1927) was an American physician born in Cleveland, Ohio, who read medicine at Harvard. He worked in Vienna under Neusser, and in Strasburg with F Kraus before returning to Cleveland. He was appointed Professor of Medicine in 1907. His main interests were in diseases of the diaphragm, lungs, and liver. Another Hoover’s sign is inward movement of the lower rib cage during inspiration, implying a flat, but functioning, diaphragm, often associated with COPD Template:Eponymous medical signs for nervous system Template:Skin and subcutaneous tissue symptoms and signs Template:Nervous and musculoskeletal system symptoms and signs Template:Urinary system symptoms and signs Template:Cognition, perception, emotional state and behaviour symptoms and signs Template:Speech and voice symptoms and signs Template:General symptoms and signs Template:WikiDoc Sources	https://www.wikidoc.org/index.php/Hoover%27s_sign
514b125851d0f1df23594924818e1f5f9e88c934	wikidoc	Hop (protein)	Hop (protein) Hop, occasionally written HOP, is an abbreviation for Hsp70-Hsp90 Organizing Protein. It functions as a co-chaperone which reversibly links together the protein chaperones Hsp70 and Hsp90. Hop belongs to the large group of co-chaperones, which regulate and assist the major chaperones (mainly heat shock proteins). It is one of the best studied co-chaperones of the Hsp70/Hsp90-complex. It was first discovered in yeast and homologues were identified in human, mouse, rat, insects, plants, parasites, and virus. The family of these proteins is referred to as STI1 (stress inducible protein) and can be divided into yeast, plant, and animal STI1 (Hop). # Synonyms # Gene The gene for human Hop is located on chromosome 11q13.1 and consists of 14 exons. # Structure STI proteins are characterized by some structural features: All homologues have nine tetratricopeptide repeat (TPR) motifs, that are clustered into domains of three TPRs. The TPR motif is a very common structural feature used by many proteins and provides the ability of directing protein-protein interactions. Crystallographic structural information is available for the N-terminal TPR1 and the central TPR2A domains in complex with Hsp90 resp. Hsp70 ligand peptides. The Hsp70-Hsp90 Organizing Protein (Hop, STIP1 in humans) is the co-chaperone responsible for the transfer of client proteins between Hsp70 and Hsp90. Hop is evolutionarily conserved in Eukaryotes and is found in both the nucleus and cytoplasm. Drosophila Hop is a monomeric protein that consists of three tetratricopeptide repeat domain regions (TPR1, TPR2A, TPR2B), one aspartic acid-proline repeat domain (DP). The TPR domains interact with the c-terminals of Hsp90 and Hsp70, with TPR1 and TPR2B binding to Hsp70 and TPR2A binding preferentially to Hsp90. The intermediate structures of heat shock machinery are difficult to characterize completely because of the transient and fast paced nature of chaperone function. # Function The main function of Hop is to link Hsp70 and Hsp90 together. But recent investigations indicate that it also modulates the chaperone activities of the linked proteins and possibly interacts with other chaperones and proteins. Apart from its role in the Hsp70/Hsp90 "chaperone machine" it seems to participate in other protein complexes too (for example in the signal transduction complex EcR/USP and in the Hepatitis B virus reverse transcriptase complex, which enables the viral replication). It acts as a receptor for prion proteins too. Hop is located in diverse cellular regions and also moves between the cytoplasm and the nucleus. In Drosophila RNA interference pathways, Hop has been shown to be an integral part of the pre-RISC complex for siRNAs. In the Drosophila Piwi-interacting RNA pathway, the RNA interference pathway responsible for the repression of transposable elements (transposons), Hop has been shown to interact with Piwi, and in the absence of Hop, transposons are derepressed, leading to severe genomic instability and infertility. # Interactions Human Hop (STIP1) has been shown to interact with PRNP and Heat shock protein 90kDa alpha (cytosolic), member A1.	Hop (protein) Hop, occasionally written HOP, is an abbreviation for Hsp70-Hsp90 Organizing Protein. It functions as a co-chaperone which reversibly links together the protein chaperones Hsp70 and Hsp90.[1] Hop belongs to the large group of co-chaperones, which regulate and assist the major chaperones (mainly heat shock proteins). It is one of the best studied co-chaperones of the Hsp70/Hsp90-complex. It was first discovered in yeast and homologues were identified in human, mouse, rat, insects, plants, parasites, and virus. The family of these proteins is referred to as STI1 (stress inducible protein) and can be divided into yeast, plant, and animal STI1 (Hop). # Synonyms # Gene The gene for human Hop is located on chromosome 11q13.1 and consists of 14 exons. # Structure STI proteins are characterized by some structural features: All homologues have nine tetratricopeptide repeat (TPR) motifs, that are clustered into domains of three TPRs. The TPR motif is a very common structural feature used by many proteins and provides the ability of directing protein-protein interactions. Crystallographic structural information is available for the N-terminal TPR1 and the central TPR2A domains in complex with Hsp90 resp. Hsp70 ligand peptides.[2] The Hsp70-Hsp90 Organizing Protein (Hop, STIP1 in humans) is the co-chaperone responsible for the transfer of client proteins between Hsp70 and Hsp90. Hop is evolutionarily conserved in Eukaryotes and is found in both the nucleus and cytoplasm[3]. Drosophila Hop is a monomeric protein that consists of three tetratricopeptide repeat domain regions (TPR1, TPR2A, TPR2B), one aspartic acid-proline repeat domain (DP). The TPR domains interact with the c-terminals of Hsp90 and Hsp70, with TPR1 and TPR2B binding to Hsp70 and TPR2A binding preferentially to Hsp90. The intermediate structures of heat shock machinery are difficult to characterize completely because of the transient and fast paced nature of chaperone function[4]. # Function The main function of Hop is to link Hsp70 and Hsp90 together. But recent investigations indicate that it also modulates the chaperone activities of the linked proteins and possibly interacts with other chaperones and proteins. Apart from its role in the Hsp70/Hsp90 "chaperone machine" it seems to participate in other protein complexes too (for example in the signal transduction complex EcR/USP and in the Hepatitis B virus reverse transcriptase complex, which enables the viral replication). It acts as a receptor for prion proteins too.[5][6] Hop is located in diverse cellular regions and also moves between the cytoplasm and the nucleus. In Drosophila RNA interference pathways, Hop has been shown to be an integral part of the pre-RISC complex for siRNAs.[7] In the Drosophila Piwi-interacting RNA pathway, the RNA interference pathway responsible for the repression of transposable elements (transposons), Hop has been shown to interact with Piwi,[8] and in the absence of Hop, transposons are derepressed, leading to severe genomic instability and infertility.[9] # Interactions Human Hop (STIP1) has been shown to interact with PRNP[10] and Heat shock protein 90kDa alpha (cytosolic), member A1.[11][12]	https://www.wikidoc.org/index.php/Hop_(protein)
0dde7df7b74dd1ecadf34c56276e7b825cc3131d	wikidoc	House healing	House healing House healings (also known as house blessings and house clearings) are rituals intended to clear a physical place of negative energies or "evil spirits". According to believers of parapsychology, a house healing entails a clairvoyant identifying energy patterns in a house or other physical structure and neutralizing them, allowing the energy of the house to align with present time vibrations. Some believers say house healings ease transitions into a new home and can cleanse a haunted house of ghost activity. House healings are not only parapsychology related; they take place in Christian, American Indian, and Pagan religions. Wiccans use a many stepped ceremony calling for herbs and the elements in order to banish unwanted spirits. House blessings are as old as Christianity, and in Catholicism, the ritual takes the form of a prayer; the practice also has a history in Eastern Orthodox and Episcopal churches. Several common superstitions in regards to house-cleaning include using a new broom for the first floor sweeping and bringing water from one's old house.	House healing House healings (also known as house blessings and house clearings) are rituals intended to clear a physical place of negative energies or "evil spirits".[1] According to believers of parapsychology, a house healing entails a clairvoyant identifying energy patterns in a house or other physical structure and neutralizing them, allowing the energy of the house to align with present time vibrations.[citation needed] Some believers say house healings ease transitions into a new home and can cleanse a haunted house of ghost activity.[2] House healings are not only parapsychology related; they take place in Christian, American Indian, and Pagan religions. Wiccans use a many stepped ceremony calling for herbs and the elements in order to banish unwanted spirits. House blessings are as old as Christianity,[1] and in Catholicism, the ritual takes the form of a prayer;[3] the practice also has a history in Eastern Orthodox and Episcopal churches.[1] Several common superstitions in regards to house-cleaning include using a new broom for the first floor sweeping and bringing water from one's old house.[citation needed]	https://www.wikidoc.org/index.php/House_healing
9303367ec34558633c1eb62b720f49f87454a1b6	wikidoc	Houston valve	Houston valve # Overview Although the term rectum means straight, the human rectum is not. There are certain permanent transverse folds, of a semilunar shape, known as Houston’s valves (or transverse folds of rectum). They project into the lumen of the rectum. These folds are about 12 mm. in width, and contain some of the circular fibers of the gut. In the empty state of the intestine they overlap each other, as Houston remarks, so effectually as to require considerable maneuvering to conduct a bougie or the finger along the canal. Their use seems to be, to support the weight of fecal matter, and prevent its urging toward the anus, where its presence always excites a sensation demanding its discharge. They are formed from circular muscle coat of the rectal wall. # Details on each fold They are usually three in number; sometimes a fourth is found, and occasionally only two are present. - One is situated near the commencement of the rectum, on the right side. - A second extends inward from the left side of the tube, opposite the middle of the sacrum. - A third, the largest and most constant, projects backward from the forepart of the rectum, opposite the fundus of the urinary bladder. - When a fourth is present, it is situated nearly 2.5 cm. above the anus on the left and posterior wall of the tube. # Clinical significance During sigmoidoscopy and colonoscopy the scope is moved around to negotiate these folds.	Houston valve # Overview Template:Infobox Anatomy Although the term rectum means straight, the human rectum is not. There are certain permanent transverse folds, of a semilunar shape, known as Houston’s valves (or transverse folds of rectum). They project into the lumen of the rectum. These folds are about 12 mm. in width, and contain some of the circular fibers of the gut. In the empty state of the intestine they overlap each other, as Houston remarks, so effectually as to require considerable maneuvering to conduct a bougie or the finger along the canal. Their use seems to be, to support the weight of fecal matter, and prevent its urging toward the anus, where its presence always excites a sensation demanding its discharge. They are formed from circular muscle coat of the rectal wall. # Details on each fold They are usually three in number; sometimes a fourth is found, and occasionally only two are present. - One is situated near the commencement of the rectum, on the right side. - A second extends inward from the left side of the tube, opposite the middle of the sacrum. - A third, the largest and most constant, projects backward from the forepart of the rectum, opposite the fundus of the urinary bladder. - When a fourth is present, it is situated nearly 2.5 cm. above the anus on the left and posterior wall of the tube. # Clinical significance During sigmoidoscopy and colonoscopy the scope is moved around to negotiate these folds. # External links - Shafik A, Doss S, Ali Y, Shafik A (2001). "Transverse folds of rectum: anatomic study and clinical implications". Clin Anat. 14 (3): 196–203. PMID 11301467.CS1 maint: Multiple names: authors list (link) .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em} Template:Gray's Template:Digestive tract Template:WH Template:WikiDoc Sources	https://www.wikidoc.org/index.php/Houston%27s_valves
c8fbe3fb00e20f122743ee7652868ac1e14c0083	wikidoc	HuD (protein)	HuD (protein) HuD otherwise known as ELAV-like protein 4 is a protein that in humans is encoded by the ELAVL4 gene. The HuD/ELAVL4 protein is an RNA-binding protein. HuD contains three RRM protein domains, enabling RNA binding. HuD is expressed only in neurons and it binds to AU-rich element-containing mRNAs. As a result of this interaction the half-life of the transcript is increased. HuD is important in neurons during brain development and plasticity. # Interactions HuD (protein) has been shown to interact with NXF1.	HuD (protein) HuD otherwise known as ELAV-like protein 4 is a protein that in humans is encoded by the ELAVL4 gene.[1][2] The HuD/ELAVL4 protein is an RNA-binding protein.[3] HuD contains three RRM protein domains, enabling RNA binding.[4] HuD is expressed only in neurons and it binds to AU-rich element-containing mRNAs. As a result of this interaction the half-life of the transcript is increased. HuD is important in neurons during brain development and plasticity.[5][6] # Interactions HuD (protein) has been shown to interact with NXF1.[7]	https://www.wikidoc.org/index.php/HuD_(protein)
66dbeff0e9312e24a0eabe1276e61106e772a290	wikidoc	Hugo De Vries	Hugo De Vries Hugo Marie de Vries (Feb 16 1848, Haarlem - May 21 1935, Lunteren) was a Dutch botanist and one of the first geneticists. He is known chiefly for suggesting the concept of genes, rediscovering Gregor Mendel's laws of heredity in the 1890s, and for developing a mutation theory of evolution. # Early life De Vries was born in 1848, the oldest son of Gerrit de Vries (1818-1900), a lawyer in Haarlem, and Maria Everardina Reuvens (1823-1914), daughter of a professor in archaeology at Leiden University. His father became a member of the Dutch Council of State in 1862 and moved his family over to The Hague. From an early age Hugo showed much interest in botany, winning several prizes for his herbariums while attending gymnasium in Haarlem and The Hague. In 1866 he enrolled at the Leiden University to major in botany. He enthusiastically took part in W.F.R. Suringar's classes and excursions, but was mostly drawn to the experimental botany outlined in Julius Sachs' 'Lehrbuch der Botanik' from 1868. He was also deeply impressed by Charles Darwin's evolution theory, despite Suringar's skepticism. He wrote a dissertation on the effect of heat on plant roots, including several statements by Darwin to provoke his professor, and graduated in 1870. # Early career After a short period of teaching, De Vries left in September 1870 to take classes in chemistry and physics at the Heidelberg University and work in the laboratory of Wilhelm Hofmeister. In the second semester of that school year he joined the lab. of the esteemed Julius Sachs in Würzburg to study plant growth. From September 1871 until 1875 he taught botany, zoology, and geology at schools in Amsterdam. During each vacation he returned to the lab in Heidelberg to continue his research. In 1875 the Prussian Ministry of Agriculture offered De Vries a position as professor at the still to be constructed Landwirtschaftliche Hochschule ("Royal Agricultural College") in Berlin. In anticipation, he moved back to Wurzburg, where he studied agricultural crops and collaborated with Sachs. By 1877, Berlin's College was still only a plan, and he briefly took up a position teaching at the University of Halle-Wittenberg. The same he year he was offered a position as lecturer in plant physiology at the newly founded University of Amsterdam. He was made adjunct professor in 1878 and full professor on his birthday in 1881, partly to keep him from moving to the Berlin College, which finally opened that year. De Vries was also professor and director of Amsterdam's Botanical Institute and Garden from 1885 to 1918. # Definition of the gene In 1889, De Vries published his book Intracellular Pangenesis , in which, based on a modified version of Charles Darwin's theory of Pangenesis of 1868, he postulated that different characters have different hereditary carriers. He specifically postulated that inheritance of specific traits in organisms comes in particles. He called these units pangenes, a term 20 years later to be shortened to genes by Wilhelm Johannsen. # Rediscovery of genetics To support his theory of pangenes, which was not widely noticed at the time, De Vries conducted a series of experiments hybridising varieties of plants in the 1890s and he discovered new forms among a display of the evening primrose (Oenothera lamarckiana) growing wild in a waste meadow. His experiments led to the same conclusions as Mendel and confirmed his hypothesis: that inheritance of specific traits in organisms comes in particles. He also speculated that genes could cross the species barrier, with the same gene being responsible for hairiness in two different species of flower. Although generally true in a sense (orthologous genes, inherited from a common ancestor of both species, tend to stay responsible for similar phenotypes), De Vries meant a physical cross between species. This actually also happens, though very rarely in higher organisms (see horizontal gene transfer). In the late 1890s, de Vries became aware of Mendel's obscure paper of forty years earlier, and he altered some of his terminology to match. When he published the results of his experiments in the French journal Comtes Rendus de l'Académie des Sciences in 1900, he neglected to mention Mendel's work, but after criticism by Carl Correns , he conceded Mendel's priority. Correns and Erich von Tschermak now share credits for the rediscovery of Mendel’s laws. It may be noteworthy that Correns was a student of Nägeli, a renowned botanist with whom Mendel corresponded about his work with peas but who failed to understand how significant Mendel's work was. Quirkily, Tschermak was a grandson of a man who taught Mendel botany during his student days in Vienna. # Mutation theory De Vries developed his own theory of evolution known as the mutation theory (a form of saltationism), which posited that instead of Darwinian gradualism, new species could arise in single jumps. However it was later discovered that much of what De Vries was describing in terms of his evidence had nothing to do with what is now known as genetic mutation. In his time, though, De Vries's theory was one of the chief contenders for the explanation of how evolution worked, until the modern evolutionary synthesis became the dominant model in the 1930s. # Honors and retirement In May 1905, De Vries was elected Foreign Member of the Royal Society. He was awarded the Darwin Medal in 1906 and the Linnean Medal in 1929. He retired in 1918 from the University of Amsterdam and withdrew to his estate "De Boeckhorst" in Lunteren where he had large experimental gardens. He continued his studies with new forms until his death in 1935. # Books His best known works are: - Intracellular Pangenesis (1889) - The Mutation Theory German edition (1900-03) English edition (1910-11) - Species and Varieties: Their Origin by Mutation (1905) - Plant Breeding (1907) German translation (1908)	Hugo De Vries Hugo Marie de Vries (Feb 16 1848, Haarlem - May 21 1935, Lunteren) was a Dutch botanist and one of the first geneticists. He is known chiefly for suggesting the concept of genes, rediscovering Gregor Mendel's laws of heredity in the 1890s, and for developing a mutation theory of evolution. # Early life De Vries was born in 1848, the oldest son of Gerrit de Vries (1818-1900), a lawyer in Haarlem, and Maria Everardina Reuvens (1823-1914), daughter of a professor in archaeology at Leiden University. His father became a member of the Dutch Council of State in 1862 and moved his family over to The Hague. From an early age Hugo showed much interest in botany, winning several prizes for his herbariums while attending gymnasium in Haarlem and The Hague. In 1866 he enrolled at the Leiden University to major in botany. He enthusiastically took part in W.F.R. Suringar's classes and excursions, but was mostly drawn to the experimental botany outlined in Julius Sachs' 'Lehrbuch der Botanik' from 1868. He was also deeply impressed by Charles Darwin's evolution theory, despite Suringar's skepticism. He wrote a dissertation on the effect of heat on plant roots, including several statements by Darwin to provoke his professor, and graduated in 1870. # Early career After a short period of teaching, De Vries left in September 1870 to take classes in chemistry and physics at the Heidelberg University and work in the laboratory of Wilhelm Hofmeister. In the second semester of that school year he joined the lab. of the esteemed Julius Sachs in Würzburg to study plant growth. From September 1871 until 1875 he taught botany, zoology, and geology at schools in Amsterdam. During each vacation he returned to the lab in Heidelberg to continue his research. In 1875 the Prussian Ministry of Agriculture offered De Vries a position as professor at the still to be constructed Landwirtschaftliche Hochschule ("Royal Agricultural College") in Berlin. In anticipation, he moved back to Wurzburg, where he studied agricultural crops and collaborated with Sachs. By 1877, Berlin's College was still only a plan, and he briefly took up a position teaching at the University of Halle-Wittenberg. The same he year he was offered a position as lecturer in plant physiology at the newly founded University of Amsterdam. He was made adjunct professor in 1878 and full professor on his birthday in 1881, partly to keep him from moving to the Berlin College, which finally opened that year. De Vries was also professor and director of Amsterdam's Botanical Institute and Garden from 1885 to 1918. # Definition of the gene In 1889, De Vries published his book Intracellular Pangenesis [1], in which, based on a modified version of Charles Darwin's theory of Pangenesis of 1868, he postulated that different characters have different hereditary carriers. He specifically postulated that inheritance of specific traits in organisms comes in particles. He called these units pangenes, a term 20 years later to be shortened to genes by Wilhelm Johannsen. # Rediscovery of genetics To support his theory of pangenes, which was not widely noticed at the time, De Vries conducted a series of experiments hybridising varieties of plants in the 1890s and he discovered new forms among a display of the evening primrose (Oenothera lamarckiana) growing wild in a waste meadow. His experiments led to the same conclusions as Mendel and confirmed his hypothesis: that inheritance of specific traits in organisms comes in particles. He also speculated that genes could cross the species barrier, with the same gene being responsible for hairiness in two different species of flower. Although generally true in a sense (orthologous genes, inherited from a common ancestor of both species, tend to stay responsible for similar phenotypes), De Vries meant a physical cross between species. This actually also happens, though very rarely in higher organisms (see horizontal gene transfer). In the late 1890s, de Vries became aware of Mendel's obscure paper of forty years earlier, and he altered some of his terminology to match. When he published the results of his experiments in the French journal Comtes Rendus de l'Académie des Sciences in 1900, he neglected to mention Mendel's work, but after criticism by Carl Correns , he conceded Mendel's priority. Correns and Erich von Tschermak now share credits for the rediscovery of Mendel’s laws. It may be noteworthy that Correns was a student of Nägeli, a renowned botanist with whom Mendel corresponded about his work with peas but who failed to understand how significant Mendel's work was. Quirkily, Tschermak was a grandson of a man who taught Mendel botany during his student days in Vienna. # Mutation theory De Vries developed his own theory of evolution known as the mutation theory (a form of saltationism), which posited that instead of Darwinian gradualism, new species could arise in single jumps. However it was later discovered that much of what De Vries was describing in terms of his evidence had nothing to do with what is now known as genetic mutation. In his time, though, De Vries's theory was one of the chief contenders for the explanation of how evolution worked, until the modern evolutionary synthesis became the dominant model in the 1930s. # Honors and retirement In May 1905, De Vries was elected Foreign Member of the Royal Society. He was awarded the Darwin Medal in 1906 and the Linnean Medal in 1929. He retired in 1918 from the University of Amsterdam and withdrew to his estate "De Boeckhorst" in Lunteren where he had large experimental gardens. He continued his studies with new forms until his death in 1935. # Books His best known works are: - Intracellular Pangenesis (1889) - The Mutation Theory German edition (1900-03) English edition (1910-11) - Species and Varieties: Their Origin by Mutation (1905) - Plant Breeding (1907) German translation (1908) Template:Botanist	https://www.wikidoc.org/index.php/Hugo_De_Vries
27b699a0c26f069b43a48aa980973309f77cd243	wikidoc	Human anatomy	Human anatomy # Overview Human anatomy, which, with physiology and biochemistry, is a complementary basic medical science is primarily the scientific study of the morphology of the adult human body. Anatomy is subdivided into gross anatomy and microscopic anatomy. Gross anatomy (also called topographical anatomy, regional anatomy, or anthropotomy) is the study of anatomical structures that can be seen by unaided vision. Microscopic anatomy is the study of minute anatomical structures assisted with microscopes, which includes histology (the study of the organization of tissues), and cytology (the study of cells). Anatomy, physiology (the study of function) and biochemistry (the study of the chemistry of living structures) are complementary basic medical sciences which are usually taught together (or in tandem). In some of its facets human anatomy is closely related to embryology, comparative anatomy and comparative embryology, through common roots in evolution; for example, much of the human body maintains the ancient segmental pattern that is present in all vertebrates with basic units being repeated, which is particularly obvious in the vertebral column and in the ribcage, and can be traced from very early embryos. The human body consists of biological systems, that consist of organs, that consist of tissues, that consist of cells and connective tissue. The history of anatomy has been characterized, over a long period of time, by a continually developing understanding of the functions of organs and structures in the body. Methods have also advanced dramatically, advancing from examination of animals through dissection of preserved cadavers (dead human bodies) to technologically complex techniques developed in the 20th century. # Study Generally, medical students, dentists, physiotherapists, nurses, paramedics, radiographers, artists, and students of certain biological sciences, learn gross anatomy and microscopic anatomy from anatomical models, skeletons, textbooks, diagrams, photographs, lectures, and tutorials. The study of microscopic anatomy (or histology) can be aided by practical experience examining histological preparations (or slides) under a microscope; and in addition, medical and dental students generally also learn anatomy with practical experience of dissection and inspection of cadavers (dead human bodies). A thorough working knowledge of anatomy is required by all medical doctors, especially surgeons, and doctors working in some diagnostic specialities, such as histopathology and radiology. Human anatomy, physiology, and biochemistry are complementary basic medical sciences, which are generally taught to medical students in their first year at medical school. Human anatomy can be taught regionally or systemically; that is, respectively, studying anatomy by bodily regions such as the head and chest, or studying by specific systems, such as the nervous or respiratory systems. The major anatomy textbook, Gray's Anatomy, has recently been reorganized from a systems format to a regional format, in line with modern teaching methods. ## Regional groups - Head and neck — includes everything above the thoracic inlet - Upper limb — includes the hand, wrist, forearm, elbow, arm, and shoulder. - Thorax — the region of the chest from the thoracic inlet to the thoracic diaphragm. - Human abdomen to the pelvic brim or to the pelvic inlet. - The back — the spine and its components, the vertebrae, sacrum, coccyx, and intervertebral disks . - Pelvis and Perineum — the pelvis consists of everything from the pelvic inlet to the pelvic diaphragm. The perineum is the region between the sex organs and the anus. - Lower limb — everything below the inguinal ligament, including the hip, the thigh, the knee, the leg, the ankle, and the foot. ## Major organ systems - Circulatory system: pumping and channeling blood to and from the body and lungs with heart, blood, and blood vessels. - Digestive system: digestion and processing food with salivary glands, esophagus, stomach, liver, gallbladder, pancreas, intestines, rectum, and anus. - Endocrine system: communication within the body using hormones made by endocrine glands such as the hypothalamus, pituitary or pituitary gland, pineal body or pineal gland, thyroid, parathyroids, and adrenals or adrenal glands - Integumentary system: skin, hair and nails - Lymphatic system: structures involved in the transfer of lymph between tissues and the blood stream, the lymph and the nodes and vessels that transport it including the Immune system: defending against disease-causing agents with leukocytes, tonsils, adenoids, thymus, and spleen - Musculoskeletal system: movement with muscles and human skeleton (structural support and protection with bones, cartilage, ligaments, and tendons). - Nervous system: collecting, transferring and processing information with brain, spinal cord, peripheral nerves, and nerves - Reproductive system: the sex organs; in the female; ovaries, fallopian tubes, uterus, vagina, mammary glands, and in the male; testes, vas deferens, seminal vesicles, prostate, and penis. - Respiratory system: the organs used for breathing, the pharynx, larynx, trachea, bronchi, lungs, and diaphragm. - Urinary system: kidneys, ureters, bladder and urethra involved in fluid balance, electrolyte balance and excretion of urine. # Superficial anatomy Superficial anatomy or surface anatomy is important in human anatomy being the study of anatomical landmarks that can be readily identified from the contours or other reference points on the surface of the body. With knowledge of superficial anatomy, physicians gauge the position and anatomy of the associated deeper structures. Common names of well known parts of the human body, from top to bottom: - Head — Forehead — Jaw — Cheek — Chin - Neck — Shoulders - Arm — Elbow — Wrist — Hand — Fingers — Thumb - Spine — Chest — Ribcage - Abdomen — Groin - Hip — Buttocks — Leg — Thigh — Knee — Calf — Heel — Ankle — Foot — Toes - The eye, ear, nose, mouth, teeth, tongue, throat, adam's apple, breast, penis, scrotum, clitoris, vulva, navel are visible too. # Internal organs Common names of internal organs (in alphabetical order) : Adrenals — Appendix — Bladder — Brain — Eyes — Gall bladder — Heart — Intestines — Kidney — Liver — Lungs — Esophagus — Ovaries — Pancreas — Parathyroids — Pituitary — Prostate — Spleen — Stomach — Testicles — Thymus — Thyroid — Uterus — Veins # Brain Amygdala — Brain stem — Cerebellum — Cerebral cortex — Limbic system — medulla — midbrain — pons	Human anatomy Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview Human anatomy, which, with physiology and biochemistry, is a complementary basic medical science is primarily the scientific study of the morphology of the adult human body.[1] Anatomy is subdivided into gross anatomy and microscopic anatomy.[1] Gross anatomy (also called topographical anatomy, regional anatomy, or anthropotomy) is the study of anatomical structures that can be seen by unaided vision.[1] Microscopic anatomy is the study of minute anatomical structures assisted with microscopes, which includes histology (the study of the organization of tissues),[1] and cytology (the study of cells). Anatomy, physiology (the study of function) and biochemistry (the study of the chemistry of living structures) are complementary basic medical sciences which are usually taught together (or in tandem). In some of its facets human anatomy is closely related to embryology, comparative anatomy and comparative embryology,[1] through common roots in evolution; for example, much of the human body maintains the ancient segmental pattern that is present in all vertebrates with basic units being repeated, which is particularly obvious in the vertebral column and in the ribcage, and can be traced from very early embryos. The human body consists of biological systems, that consist of organs, that consist of tissues, that consist of cells and connective tissue. The history of anatomy has been characterized, over a long period of time, by a continually developing understanding of the functions of organs and structures in the body. Methods have also advanced dramatically, advancing from examination of animals through dissection of preserved cadavers (dead human bodies) to technologically complex techniques developed in the 20th century. # Study Generally, medical students, dentists, physiotherapists, nurses, paramedics, radiographers, artists, and students of certain biological sciences, learn gross anatomy and microscopic anatomy from anatomical models, skeletons, textbooks, diagrams, photographs, lectures, and tutorials. The study of microscopic anatomy (or histology) can be aided by practical experience examining histological preparations (or slides) under a microscope; and in addition, medical and dental students generally also learn anatomy with practical experience of dissection and inspection of cadavers (dead human bodies). A thorough working knowledge of anatomy is required by all medical doctors, especially surgeons, and doctors working in some diagnostic specialities, such as histopathology and radiology. Human anatomy, physiology, and biochemistry are complementary basic medical sciences, which are generally taught to medical students in their first year at medical school. Human anatomy can be taught regionally or systemically;[1] that is, respectively, studying anatomy by bodily regions such as the head and chest, or studying by specific systems, such as the nervous or respiratory systems. The major anatomy textbook, Gray's Anatomy, has recently been reorganized from a systems format to a regional format,[2][3] in line with modern teaching methods. ## Regional groups - Head and neck — includes everything above the thoracic inlet - Upper limb — includes the hand, wrist, forearm, elbow, arm, and shoulder. - Thorax — the region of the chest from the thoracic inlet to the thoracic diaphragm. - Human abdomen to the pelvic brim or to the pelvic inlet. - The back — the spine and its components, the vertebrae, sacrum, coccyx, and intervertebral disks . - Pelvis and Perineum — the pelvis consists of everything from the pelvic inlet to the pelvic diaphragm. The perineum is the region between the sex organs and the anus. - Lower limb — everything below the inguinal ligament, including the hip, the thigh, the knee, the leg, the ankle, and the foot. ## Major organ systems - Circulatory system: pumping and channeling blood to and from the body and lungs with heart, blood, and blood vessels. - Digestive system: digestion and processing food with salivary glands, esophagus, stomach, liver, gallbladder, pancreas, intestines, rectum, and anus. - Endocrine system: communication within the body using hormones made by endocrine glands such as the hypothalamus, pituitary or pituitary gland, pineal body or pineal gland, thyroid, parathyroids, and adrenals or adrenal glands - Integumentary system: skin, hair and nails - Lymphatic system: structures involved in the transfer of lymph between tissues and the blood stream, the lymph and the nodes and vessels that transport it including the Immune system: defending against disease-causing agents with leukocytes, tonsils, adenoids, thymus, and spleen - Musculoskeletal system: movement with muscles and human skeleton (structural support and protection with bones, cartilage, ligaments, and tendons). - Nervous system: collecting, transferring and processing information with brain, spinal cord, peripheral nerves, and nerves - Reproductive system: the sex organs; in the female; ovaries, fallopian tubes, uterus, vagina, mammary glands, and in the male; testes, vas deferens, seminal vesicles, prostate, and penis. - Respiratory system: the organs used for breathing, the pharynx, larynx, trachea, bronchi, lungs, and diaphragm. - Urinary system: kidneys, ureters, bladder and urethra involved in fluid balance, electrolyte balance and excretion of urine. # Superficial anatomy Superficial anatomy or surface anatomy is important in human anatomy being the study of anatomical landmarks that can be readily identified from the contours or other reference points on the surface of the body.[1] With knowledge of superficial anatomy, physicians gauge the position and anatomy of the associated deeper structures. Common names of well known parts of the human body, from top to bottom: - Head — Forehead — Jaw — Cheek — Chin - Neck — Shoulders - Arm — Elbow — Wrist — Hand — Fingers — Thumb - Spine — Chest — Ribcage - Abdomen — Groin - Hip — Buttocks — Leg — Thigh — Knee — Calf — Heel — Ankle — Foot — Toes - The eye, ear, nose, mouth, teeth, tongue, throat, adam's apple, breast, penis, scrotum, clitoris, vulva, navel are visible too. # Internal organs Common names of internal organs (in alphabetical order) : Adrenals — Appendix — Bladder — Brain — Eyes — Gall bladder — Heart — Intestines — Kidney — Liver — Lungs — Esophagus — Ovaries — Pancreas — Parathyroids — Pituitary — Prostate — Spleen — Stomach — Testicles — Thymus — Thyroid — Uterus — Veins # Brain Amygdala — Brain stem — Cerebellum — Cerebral cortex — Limbic system — medulla — midbrain — pons	https://www.wikidoc.org/index.php/Human_anatomy
58b00209165bb57c19e3cea923b76aba24e0b063	wikidoc	Human biology	Human biology # Overview Human biology is an interdisciplinary academic field of biology, biological anthropology, and medicine which focuses on humans; it is closely related to primate biology, and a number of other fields. The human biology major was founded in 1970 at Stanford University. Human biology research encompasses: - Genetic variation across human populations, present and past - Biological variation related to climate and other elements of the natural environment - Determinants, across populations, of risk for degenerative disease and infectious disease - Human growth and development - Biodemography While undissputed boundaries do not exist, human biology is typically distinguished from conventional medical research by an enhanced focus on international, population-level perspectives on health, and on human evolution, adaptation, and population genetics rather than individual diagnosis.	Human biology # Overview Human biology is an interdisciplinary academic field of biology, biological anthropology, and medicine which focuses on humans; it is closely related to primate biology, and a number of other fields. The human biology major was founded in 1970 at Stanford University. Human biology research encompasses: - Genetic variation across human populations, present and past - Biological variation related to climate and other elements of the natural environment - Determinants, across populations, of risk for degenerative disease and infectious disease - Human growth and development - Biodemography While undissputed boundaries do not exist, human biology is typically distinguished from conventional medical research by an enhanced focus on international, population-level perspectives on health, and on human evolution, adaptation, and population genetics rather than individual diagnosis. # External links - Human Biology Association - Society for the Study of Human Biology Symposium Series Template:Biology-footer Template:Human ar:علم الأحياء البشري an:Biolochía umana da:Humanbiologi de:Humanbiologie ko:인간생물학 is:Líffræði mannsins lt:Žmogaus biologija nl:Menselijke biologie no:Humanbiologi nov:Homal biologia simple:Human biology Template:WikiDoc Sources Template:WH	https://www.wikidoc.org/index.php/Human_biology
1a4603c9d735551f77f4cd03c24ab6b352fcd167	wikidoc	Human bonding	Human bonding The term human bond -- or, more generally, human bonding -- refers to the process or formation of a close personal relationship, as between a parent and child, especially through frequent or constant association. When pairs have favorable bonds, the nature of this bonding is usually attributed to "good" interpersonal chemistry. The word bond derives from the 12th century Middle English word band, meaning something that binds, ties, or restrains. Its application to interpersonal human relationships has been used intermittently ever since. The term social network or "interconnected group of people", which may include up to 150 people (Dunbar's number), is from 1947. The concept of nuclear family or bonded unit of two parents plus one or more children was coined by American anthropologist George Murdock in his 1949 work Social Structure. According to Merriam-Webster, the application of the term “bonding” to interpersonal relationships came of use in 1976. With the recent popularity of the Internet, sites such as MySpace encourage people to increase the size of their friendship networks. # Early views In the 4th century BC, the Greek philosopher Plato argues that love, in a way, directs the bonds of human society. In his Symposium, Eryximachus, one of the narrators in the dialog, states that love goes far beyond simple attraction to human beauty: It occurs all throughout the animal and plant kingdoms, as well as all throughout the universe. Love directs everything that occurs, in the realm of the gods as well as that of humans (186a-b). Eyrximachus reasons that when various opposing elements such as wet and dry are "animated by the proper species of Love, they are in harmony with one another . . . But when the sort of Love that is crude and impulsive controls the seasons, he brings death and destruction" (188a). As it is love that guides the relations between these sets of opposites throughout existence, in every case it is the higher form of love that brings harmony and cleaves toward the good, while the impulsive vulgar love creates disharmony. He concludes that the highest form of love is the greatest; when love "is directed, in temperance and justice, towards the good, whether in heaven or on earth: happiness and good fortune, the bonds of human society, concord with the gods above- all these are among his gifts" (188d). In the 1660s, the Dutch philosopher Spinoza writes, in his Ethics of Human Bondage or the Strength of the Emotions, that the term “bondage” relates to the human infirmity in moderating and checking the emotions. That is, according to Spinoza ‘when a man is prey to his emotions, he is not his own master, but lies at the mercy of fortune.’ In 1809 Johann Wolfgang von Goethe, in his classic novella Elective Affinities, speaks of the marriage tie and by analogy shows how strong marriage unions are similar in character to that by which the particles of quicksilver find a unity together though the process of chemical affinity. Goethe’s novella, in its time, was regarded as treatise on chemical origins of love. Humans in passionate relationships, according to Goethe, are analogous to reactive substances in a chemical equation. # Bond varieties The term “bonding” applies aptly to all variations of connections within interpersonal relationships, social networks, economic nexuses, political ties, etc. The term male bonding refers to bonding between males through shared activities excluding females or the formation of a close personal relationship between men; for example: "the rituals known as male bonding do not necessarily involve drinking beer together". The analog concept female bonding, although less frequently used, refers to the formation of a close personal relationship between women. The familial bond defines as a uniting force, tie, or link between related family members. A related concept is bondage, being the tenure of service of a villager, serf, or slave and generally refers to a state of being bound by compulsion as via law or mastery; a bondmaid is a woman servant, a bondman is a male servant, and a bondsman is a person who provides bonds or surety for another. In the 14th century, a bondwoman was considered a female slave. The distinction is that "bonding" almost always implies a voluntary act, of entering in or remaining in relationship from a wish to do so. A comparable analog is labor union, originating in 1866, being an organization of united workers formed for the purpose of advancing its members’ interests in respect to wages, benefits, and working conditions. The cohesion of the group is facilitated by the exchange of union dues for benefits. By uniting, the bonded group has more leverage than as compared to a collection of separate individuals. Similar to the marriage bond, is concept of civil union. A civil union is one of several terms for a civil status similar to marriage, typically created for the purposes of allowing same-sex couples access to the benefits enjoyed by married opposite-sex peoples (see also same-sex marriage); it can also be used by opposite-sex couples who do not prefer to enter into the legal institution of marriage but who would rather be in a union more similar to a common-law marriage. With the popular success of the hit television show Queer Eye For The Straight Guy and others such as The Ellen DeGeneres Show, the term gay-straight bonding as well as gay bonding have come into vogue. ## Other - Connector - people in a community who know large numbers of people and who are in the habit of making introductions. - Homophily, i.e., love of the same, is the tendency of individuals to associate and "bond" with similar others. - Gemeinschaft - a spontaneous organic social relationship characterized by strong reciprocal "bonds" of sentiment and kinship with in a common tradition. - Clique - an informal and restricted social group formed by people who share common interests, which are often associated with teenagers. - Mother-bonded - a term for a man who is excessively attached to his mother at an age when men are expected to be independent, e.g. living on their own, being economically independent, etc. # Interpersonal chemistry Metaphorically, a chemical reaction between two people involves either the formation of a bond or dissolution of a bond, or some combination thereof, and the psychodynamics associated with this process. In this direction, in the fields of sociology, behavioral psychology, and evolutionary psychology, with specific reference to intimate relationships or romantic relationships, interpersonal chemistry is a reaction between two people or the spontaneous reaction of two people to each other, especially a mutual sense of attraction or understanding. In a colloquial sense, it is often intuited that people can have either good chemistry or bad chemistry together. Other related terms are team chemistry, a phrase often used in sports, and business chemistry, as between two companies. Recent developments in neurochemistry have begun to shed light on the nature of the "chemistry of love", in terms of measurable changes in neurotransmitters such as oxytocin, serotonin, and dopamine. # Bond distinctions A common division when referring to the structural integrity of relationships or unions is to divide such bonds via a physical and a neurological component, which may or may not co-occur, i.e. into: - Physical bond – two people bonded owing to physical adhesion. - Neurological bond – two people bonded owing to neurological adhesion. The physical bond is typically sexual in nature, i.e. a sexual bond, although it may refer to individuals bonded by proximity as neighbors or by blood as siblings. People bonded physically typically have a visceral connection, either via pheromone exchange, visual attraction, hormonal adhesion, etc. The neurological bond covers all varieties of mental attachment, as psychological bonds, intellectual bonds, emotional bonds, financial bonds, synergistic bonds, altruistic bonds, etc. In 1939 psychologist Godfrey Thomson, in his Factorial Analysis of Human Ability, for example, posited theoretical “bonds” of intelligence which function in loving relationships. In Sternberg’s 1986 Triangular Theory of Love, he defined Thomson’s theory as a structural model of love where we might conceptualize love in terms of feelings that, when sampled together, yield the composite experience that we label love. Here, the composite is not an undifferentiated unity; rather, it can be decomposed into a large number of underlying bonds that tend to co-occur in certain close relationships. With reference to the triangle theory, Sternberg relates the passion component of his triangle to the physical bond and the intimacy and decision/commitment components of the triangle to the neurological bond, both of which vary in strength and intensity throughout each stage of the relationship, i.e. dating, transition, marriage, etc. Similarly, in recent the 2006 National Geographic article “Love the Chemical Reaction” photo journalist Lauren Slater asks: “Does passion necessarily diminish over time? Can a marriage be good when Eros is replaced with friendship, or even economic partnership, two people bound by bank accounts?” Referring to her eight-year marriage, she states: “The ties that bind have been frayed by money and mortgages and children, those little imps who somehow manage to tighten the knot while weakening its actual fibers.” # Neurochemistry Main bonding chemicals - Oxytocin – bonding molecule (hormone): high levels correlate with strong pair-bonding. - Vasopressin – monogamy molecule (hormone) - Endorphin - calming natural pain killer Related bonding chemicals - PEA – amphetamine molecule (neurotransmitter) - Dopamine – desire molecule (neurotransmitter): levels increase as passion levels increase. - Serotonin – stability molecule (neurotransmitter) - DHEA – most abundant hormone - Prolactin – motherly hormone (stops female and male sex-drive) - Testosterone – masculinization hormone (high testosterone-laden males tend to bond with high estrogen-laden females) - Cortisol - the primary hormone product of the adrenal glands; helps restore homeostasis after a state of stress. - Estrogen – feminization hormone (high estrogen-laden females tend to bond with high testosterone-laden males) - Androsterone – a pheromone attractor - Squalene – a pheromone repellant (stops male courtship behavior in snakes) - Progesterone – reverse sex-drive hormone - Norepinephrine - elevated levels are associated with romantic love. - Nerve growth factor - neuro-protein that stimulates cell growth; higher levels are found with those newly in love as compared to those single or in long-term relationships. Related facts - The ventral tegmental area and the caudate nucleus become more active when madly in love. - When looking at a lover’s photo the anterior cingulated cortex and the basal ganglia become more active. - When looking at a lover’s photo the posterior cingulated gyrus and the right pre-frontal cortex become less active. - During the first six months of love, serotonin levels drop to 40 percent below those in normal subjects. - Women are vomeronasally-attracted to men with dissimilar major histocompatibility complexes. - Males in love have decreased levels of follicle-stimulating hormone (FSH). In men, FSH enhances the production of androgen-binding protein by the Sertoli cells of the testes and is critical for spermatogenesis. # Types ## Pair bond Pair-bond, originating in 1940 in reference to birds in mating, is a generic term signifying a monogamous relationship or a socially monogamous relationship of either the human or animal variety, commonly used in sociobiology and evolutionary psychology. Pair-bonding, usually of a fairly short duration, occurs in a variety of primate species. Some scientists speculate that prolonged bonds developed in humans along with increased sharing of food. In recent years, some have begun to apply the term to human relationships arguing, for example, that a recent shift in technology, namely birth control and DNA testing, have created a shift in the male-female power balance thus resulting in the formation of dynamic pair-bond that do not exist in other species. ## Maternal bond Of all human bonds, the mother-infant bond or maternal bond is the first to develop and considered to be one of the strongest. The maternal bond begins to develop during pregnancy; following pregnancy, the production of oxytocin during lactation increases parasympathetic activity, thus reducing anxiety and theoretically fostering bonding. It is generally understood that maternal oxytocin circulation can predispose some mammals to show caregiving behavior in response to young of their species. Breastfeeding has been reported to foster the early post-partum maternal bond, via touch, response, and mutual gazing.. This effect is not universal, however, especially if problems with breastfeeding occur. It is difficult to determine the extent of causality due to a number of confounding variables, such as the varied reasons families choose different feeding methods. Many believe that early bonding ideally increases response and sensitivity to the child's needs, bolstering the quality of the mother-baby relationship – however, many exceptions can be found of highly successful mother-baby bonds, even though early breastfeeding did not occur, such as with premature infants who may lack the necessary sucking strength to successfully breastfeed. ## Paternal bond In contrast to the maternal bond, in terms of variation in strength and stability, the father-infant bond or paternal bond tends to vary greatly over the lifespan of a child’s development and growth and in many cases does not exist. Many children, for example, in modern times, grow up in fatherless households. In general, paternal bonding is more dominant later in a child’s life after language develops. Father-child bonds tend to develop with respect to topics and areas such as political views or money; whereas mother-child bonds tend to develop in relation to topics such as religious views or general outlooks on life. In 2003, researcher from Northwestern University in Illinois found that progesterone, a hormone more usually associated with pregnancy and maternal bonding, may also control the way men react towards their children. Specifically, they found that a lack of progesterone reduced aggressive behaviour in male mice and stimulated them to act in a fatherly way towards their offspring. ## Affectional bond In 1958, British developmental psychologist John Bowlby published the ground-breaking paper "the Nature of the Child's Tie to his Mother", in which the precursory concepts of "attachment" were developed. This later led to the development of the concept of the affectional bond, sometimes referred to as the emotional bond, which is based on the universal tendency for humans to attach, i.e. to seek closeness to another person and to feel secure when that person is present. Attachment theory has its origins in the observation of and experiments with animals. Much of the early research on attachment in humans was done by John Bowlby and his associates. Bowlby proposed that babies have an inbuilt need from birth to make emotional attachments, i.e. bonds, because this increases the chances of survival by ensuring that they receive the care they need. ## Weak ties In 1962, Mark Granovetter, a freshman history major at Harvard, became enamored with the concepts underlying the classic chemistry lecture in which "weak" hydrogen bonds hold huge water molecule together, which themselves are held together by "strong" covalent bonds. This model was the stimulus behind his famous 1973 paper The Strength of the Weak Tie, which is now considered a classic paper in sociology. Thus, weak social ties, or weak ties, it is argued, are responsible for the majority of the embeddedness and structure of social networks in society as well as the transmission of information through these networks. Specifically, more novel information flows to individuals through weak than through strong ties. Because our close friends tend to move in the same circles that we do, the information they receive overlaps considerably with what we already know. Acquaintances, by contrast, know people that we do not, and thus receive more novel information. ## Limerent bond According to limerence theory, positioned in 1979 by psychologist Dorothy Tennov, a certain percentage of couples may go through what is called a limerent reaction, in which one or both of the pair may experience a state of passion mixed with continuous intrusive thinking, fear of rejection, and hope. Hence, with all human romantic relationships, one of three varieties of bonds may form, defined over a set duration of time, in relation to the experience or non-experience of limerence: - Affectional bond: define relationships in which neither partner is limerent. - Limerent-Nonlimerent bond: define relationships in which one partner is limerent. - Limerent-Limerent bond: define relationships in which both partners are limerent. The constitution of these bonds may vary over the course of the relationship, in ways that may either increase or decrease the intensity of the limerence. The basis and interesting characteristic of this delineation made by Tennov, is that based on her research and interviews with over 500 people, all human bonded relationships can be divided into three varieties being defined by the amount of limerence or non-limerence each partner contributes to the relationship. ## Erotic bond In the 1988 book Love Maps psychologist John Money postulated the existence of the erotic bond. According to Money, each person is theorized to have a correlative love map based on his or her upbringing and experiences. This concept is frequently referenced in interpersonal-relationship discussions. A love map may make note of both positive and negative factors, things that attract or repel the person whose erotic tastes are being mapped. For reasons that are not always easy to understand, one person may be attracted to people of a particular gender, people with particular physical characteristics (such as hair color), people with particular personality traits (e.g., a sardonic sense of humor), and so forth. One may also find certain characteristics so threatening or objectionable (again, for reasons that may be difficult or impossible to ascertain) that it strongly mitigates against an erotic attraction being manifested. Using this love map, a person unconsciously makes note of the personal and environmental factors that facilitate the formation of an erotic bond. ## Limbic bond In 2000, psychologists Lewis, Amini, and Lannon published their famous A General Theory of Love in which they postulated the concept of the limbic bond, which defines a bodily connection that is limbic in nature. They also refer to this bond as a mammalian bond being that mammals in contrast to reptiles have a limbic system, which is why reptiles abandon their young after birth whereas mammals do not. In the limbic bond, a mutually synchronizing sensory exchange as bodily warmth, olfactory cues, vocal exchange, visual interactions, etc., function to keep ties or organizing sensory channels between connected individuals. These ties or bonds function to regulate those associated persons. They define this design as an open-loop regulatory system; where, as they state, adults are social animals: they continue to require a source of stabilization outside themselves. The open loop design means that in some important ways, people cannot be stable on their own; stability means finding people who regulate you well and staying near them. ## Societal bond The societal bond refers to those cohesive elements and structural ties, as economic activity, unions, trade, sanctions, etc., which function to bind societies into collective units. According to encyclopedia.com, marriage functions to cement the societal bond. As they state, in many societies marriage links not just nuclear families but larger social formations as well. Some endogamous societies are divided into exogamous groups, as clans or lineages. Here, men form alliances through exchange of women, and the social organization regulates these alliances through marriage rules. ## Human-animal bond The human-animal bond can be defined as a connection between people and animals, domestic or wild; be it a cat as a pet or birds outside one’s window. Research into the nature and merit of the human animal bond began in the late 1700s when, in York, England, the Society of Friends established the The Retreat to provide humane treatment for the mentally ill. By having patients care for the many farm animals on the estate, society officials theorized that the combination of animal contact plus productive work would facilitate the patients’ rehabilitation. In the 1870s in Paris, a French surgeon had patients with neurological disorders ride horses. The patients were found to have improved their motor control and balance and were less likely to suffer bouts of depression. In the 19th century, in Bielefeld, Germany, epileptic patients were given the prescription to spend time each day taking care of cats and dogs. The contact with the animals was found to reduce the occurrence of seizures. In 1980, a team of scientists at the University of Pennsylvania found that human to animal contact was found to reduce the physiological characteristics of stress; specifically, lowered levels of blood pressure, heart rate, respiratory rate, anxiety, and tension were all found to correlate positively with human pet bonding. Historically, animals were domesticated for functional use; for example, dogs for herding and tracking, and cats for killing mice or rats. Today, in Western societies, their function is primarily a bonding function. For example, current studies show that 60-80% of dogs sleep with their owners at night in the bedroom, either in or on the bed. Moreover, in the past the majority of cats were kept outside (barn cats) whereas today most cats are kept indoors (housecats) and considered part of the family. Presently, in the US, for example, 1.2 billion animals are kept as pets, primarily for bonding purposes. In addition, as of 1995 there were over 30 research institutions looking into the potential benefits of the human animal bond. # Debonding In 1976, sociologist Diane Vaughan proposed an “uncoupling theory”, where, during the dynamics of relationship breakup, there exists "turning point", only noted in hindsight, followed by transition period in which one partner unconsciously knows the relationship is going to end, but holds on to it for an extended period, sometimes for a number of years.	Human bonding Template:Accuracy Template:Close Relationships The term human bond -- or, more generally, human bonding -- refers to the process or formation of a close personal relationship, as between a parent and child, especially through frequent or constant association.[1] When pairs have favorable bonds, the nature of this bonding is usually attributed to "good" interpersonal chemistry. The word bond derives from the 12th century Middle English word band, meaning something that binds, ties, or restrains. Its application to interpersonal human relationships has been used intermittently ever since. The term social network or "interconnected group of people", which may include up to 150 people (Dunbar's number), is from 1947.[2] The concept of nuclear family or bonded unit of two parents plus one or more children was coined by American anthropologist George Murdock in his 1949 work Social Structure.[3] According to Merriam-Webster, the application of the term “bonding” to interpersonal relationships came of use in 1976. With the recent popularity of the Internet, sites such as MySpace encourage people to increase the size of their friendship networks.[4] # Early views In the 4th century BC, the Greek philosopher Plato argues that love, in a way, directs the bonds of human society. In his Symposium, Eryximachus, one of the narrators in the dialog, states that love goes far beyond simple attraction to human beauty: It occurs all throughout the animal and plant kingdoms, as well as all throughout the universe. Love directs everything that occurs, in the realm of the gods as well as that of humans (186a-b). Eyrximachus reasons that when various opposing elements such as wet and dry are "animated by the proper species of Love, they are in harmony with one another . . . But when the sort of Love that is crude and impulsive controls the seasons, he brings death and destruction" (188a). As it is love that guides the relations between these sets of opposites throughout existence, in every case it is the higher form of love that brings harmony and cleaves toward the good, while the impulsive vulgar love creates disharmony. He concludes that the highest form of love is the greatest; when love "is directed, in temperance and justice, towards the good, whether in heaven or on earth: happiness and good fortune, the bonds of human society, concord with the gods above- all these are among his gifts" (188d). In the 1660s, the Dutch philosopher Spinoza writes, in his Ethics of Human Bondage or the Strength of the Emotions, that the term “bondage” relates to the human infirmity in moderating and checking the emotions. That is, according to Spinoza ‘when a man is prey to his emotions, he is not his own master, but lies at the mercy of fortune.’ In 1809 Johann Wolfgang von Goethe, in his classic novella Elective Affinities, speaks of the marriage tie and by analogy shows how strong marriage unions are similar in character to that by which the particles of quicksilver find a unity together though the process of chemical affinity. Goethe’s novella, in its time, was regarded as treatise on chemical origins of love. Humans in passionate relationships, according to Goethe, are analogous to reactive substances in a chemical equation. # Bond varieties The term “bonding” applies aptly to all variations of connections within interpersonal relationships, social networks, economic nexuses, political ties, etc. The term male bonding refers to bonding between males through shared activities excluding females or the formation of a close personal relationship between men; for example: "the rituals known as male bonding do not necessarily involve drinking beer together".[6] The analog concept female bonding, although less frequently used, refers to the formation of a close personal relationship between women.[7] The familial bond defines as a uniting force, tie, or link between related family members.[8] A related concept is bondage, being the tenure of service of a villager, serf, or slave and generally refers to a state of being bound by compulsion as via law or mastery; a bondmaid is a woman servant, a bondman is a male servant, and a bondsman is a person who provides bonds or surety for another. In the 14th century, a bondwoman was considered a female slave. The distinction is that "bonding" almost always implies a voluntary act, of entering in or remaining in relationship from a wish to do so. A comparable analog is labor union, originating in 1866, being an organization of united workers formed for the purpose of advancing its members’ interests in respect to wages, benefits, and working conditions. The cohesion of the group is facilitated by the exchange of union dues for benefits. By uniting, the bonded group has more leverage than as compared to a collection of separate individuals. Similar to the marriage bond, is concept of civil union. A civil union is one of several terms for a civil status similar to marriage, typically created for the purposes of allowing same-sex couples access to the benefits enjoyed by married opposite-sex peoples (see also same-sex marriage); it can also be used by opposite-sex couples who do not prefer to enter into the legal institution of marriage but who would rather be in a union more similar to a common-law marriage. With the popular success of the hit television show Queer Eye For The Straight Guy and others such as The Ellen DeGeneres Show, the term gay-straight bonding as well as gay bonding have come into vogue.[9] ## Other - Connector - people in a community who know large numbers of people and who are in the habit of making introductions. - Homophily, i.e., love of the same, is the tendency of individuals to associate and "bond" with similar others. - Gemeinschaft - a spontaneous organic social relationship characterized by strong reciprocal "bonds" of sentiment and kinship with in a common tradition.[10] - Clique - an informal and restricted social group formed by people who share common interests, which are often associated with teenagers. - Mother-bonded - a term for a man who is excessively attached to his mother at an age when men are expected to be independent, e.g. living on their own, being economically independent, etc.[11] # Interpersonal chemistry Metaphorically, a chemical reaction between two people involves either the formation of a bond or dissolution of a bond, or some combination thereof, and the psychodynamics associated with this process.[12][13] In this direction, in the fields of sociology, behavioral psychology, and evolutionary psychology, with specific reference to intimate relationships or romantic relationships, interpersonal chemistry is a reaction between two people or the spontaneous reaction of two people to each other, especially a mutual sense of attraction or understanding.[14] In a colloquial sense, it is often intuited that people can have either good chemistry or bad chemistry together. Other related terms are team chemistry, a phrase often used in sports, and business chemistry, as between two companies.[15] Recent developments in neurochemistry have begun to shed light on the nature of the "chemistry of love", in terms of measurable changes in neurotransmitters such as oxytocin, serotonin, and dopamine. # Bond distinctions A common division when referring to the structural integrity of relationships or unions is to divide such bonds via a physical and a neurological component, which may or may not co-occur, i.e. into: - Physical bond – two people bonded owing to physical adhesion. - Neurological bond – two people bonded owing to neurological adhesion. The physical bond is typically sexual in nature, i.e. a sexual bond, although it may refer to individuals bonded by proximity as neighbors or by blood as siblings. People bonded physically typically have a visceral connection, either via pheromone exchange, visual attraction, hormonal adhesion, etc. The neurological bond covers all varieties of mental attachment, as psychological bonds, intellectual bonds, emotional bonds, financial bonds, synergistic bonds, altruistic bonds, etc. In 1939 psychologist Godfrey Thomson, in his Factorial Analysis of Human Ability, for example, posited theoretical “bonds” of intelligence which function in loving relationships. In Sternberg’s 1986 Triangular Theory of Love, he defined Thomson’s theory as a structural model of love where we might conceptualize love in terms of feelings that, when sampled together, yield the composite experience that we label love. Here, the composite is not an undifferentiated unity; rather, it can be decomposed into a large number of underlying bonds that tend to co-occur in certain close relationships. With reference to the triangle theory, Sternberg relates the passion component of his triangle to the physical bond and the intimacy and decision/commitment components of the triangle to the neurological bond, both of which vary in strength and intensity throughout each stage of the relationship, i.e. dating, transition, marriage, etc. Similarly, in recent the 2006 National Geographic article “Love the Chemical Reaction” photo journalist Lauren Slater asks: “Does passion necessarily diminish over time? Can a marriage be good when Eros is replaced with friendship, or even economic partnership, two people bound by bank accounts?” Referring to her eight-year marriage, she states: “The ties that bind have been frayed by money and mortgages and children, those little imps who somehow manage to tighten the knot while weakening its actual fibers.” # Neurochemistry Main bonding chemicals[17][18] - Oxytocin [C43H66N12O12S2] – bonding molecule (hormone): high levels correlate with strong pair-bonding. - Vasopressin – monogamy molecule (hormone) - Endorphin - calming natural pain killer Related bonding chemicals[17][18] - PEA [C8H11N] – amphetamine molecule (neurotransmitter) - Dopamine [C8H11NO2] – desire molecule (neurotransmitter): levels increase as passion levels increase. - Serotonin [C10H12N2O] – stability molecule (neurotransmitter) - DHEA [C19H28O2] – most abundant hormone - Prolactin – motherly hormone (stops female and male sex-drive) - Testosterone [C19H28O2] – masculinization hormone (high testosterone-laden males tend to bond with high estrogen-laden females) - Cortisol - the primary hormone product of the adrenal glands; helps restore homeostasis after a state of stress. - Estrogen – feminization hormone (high estrogen-laden females tend to bond with high testosterone-laden males) - Androsterone [C19H30O2] – a pheromone attractor - Squalene [C30H50] – a pheromone repellant (stops male courtship behavior in snakes) - Progesterone [C21H30O2] – reverse sex-drive hormone - Norepinephrine [C8H11NO3] - elevated levels are associated with romantic love.[20] - Nerve growth factor - neuro-protein that stimulates cell growth; higher levels are found with those newly in love as compared to those single or in long-term relationships.[22] Related facts[23][18] - The ventral tegmental area and the caudate nucleus become more active when madly in love. - When looking at a lover’s photo the anterior cingulated cortex and the basal ganglia become more active. - When looking at a lover’s photo the posterior cingulated gyrus and the right pre-frontal cortex become less active. - During the first six months of love, serotonin levels drop to 40 percent below those in normal subjects. - Women are vomeronasally-attracted to men with dissimilar major histocompatibility complexes. - Males in love have decreased levels of follicle-stimulating hormone (FSH).[21] In men, FSH enhances the production of androgen-binding protein by the Sertoli cells of the testes and is critical for spermatogenesis. # Types ## Pair bond Pair-bond, originating in 1940 in reference to birds in mating, is a generic term signifying a monogamous relationship or a socially monogamous relationship of either the human or animal variety, commonly used in sociobiology and evolutionary psychology.[24] Pair-bonding, usually of a fairly short duration, occurs in a variety of primate species. Some scientists speculate that prolonged bonds developed in humans along with increased sharing of food.[25] In recent years, some have begun to apply the term to human relationships arguing, for example, that a recent shift in technology, namely birth control and DNA testing, have created a shift in the male-female power balance thus resulting in the formation of dynamic pair-bond that do not exist in other species.[26] ## Maternal bond Of all human bonds, the mother-infant bond or maternal bond is the first to develop and considered to be one of the strongest. The maternal bond begins to develop during pregnancy; following pregnancy, the production of oxytocin during lactation increases parasympathetic activity, thus reducing anxiety and theoretically fostering bonding. It is generally understood that maternal oxytocin circulation can predispose some mammals to show caregiving behavior in response to young of their species. Breastfeeding has been reported to foster the early post-partum maternal bond, via touch, response, and mutual gazing.[27]. This effect is not universal, however, especially if problems with breastfeeding occur. It is difficult to determine the extent of causality due to a number of confounding variables, such as the varied reasons families choose different feeding methods. Many believe that early bonding ideally increases response and sensitivity to the child's needs, bolstering the quality of the mother-baby relationship – however, many exceptions can be found of highly successful mother-baby bonds, even though early breastfeeding did not occur, such as with premature infants who may lack the necessary sucking strength to successfully breastfeed. ## Paternal bond In contrast to the maternal bond, in terms of variation in strength and stability, the father-infant bond or paternal bond tends to vary greatly over the lifespan of a child’s development and growth and in many cases does not exist. Many children, for example, in modern times, grow up in fatherless households. In general, paternal bonding is more dominant later in a child’s life after language develops. Father-child bonds tend to develop with respect to topics and areas such as political views or money; whereas mother-child bonds tend to develop in relation to topics such as religious views or general outlooks on life.[28] In 2003, researcher from Northwestern University in Illinois found that progesterone, a hormone more usually associated with pregnancy and maternal bonding, may also control the way men react towards their children. Specifically, they found that a lack of progesterone reduced aggressive behaviour in male mice and stimulated them to act in a fatherly way towards their offspring.[29] ## Affectional bond In 1958, British developmental psychologist John Bowlby published the ground-breaking paper "the Nature of the Child's Tie to his Mother", in which the precursory concepts of "attachment" were developed. This later led to the development of the concept of the affectional bond, sometimes referred to as the emotional bond, which is based on the universal tendency for humans to attach, i.e. to seek closeness to another person and to feel secure when that person is present. Attachment theory has its origins in the observation of and experiments with animals. Much of the early research on attachment in humans was done by John Bowlby and his associates. Bowlby proposed that babies have an inbuilt need from birth to make emotional attachments, i.e. bonds, because this increases the chances of survival by ensuring that they receive the care they need.[30][12][18] ## Weak ties In 1962, Mark Granovetter, a freshman history major at Harvard, became enamored with the concepts underlying the classic chemistry lecture in which "weak" hydrogen bonds hold huge water molecule together, which themselves are held together by "strong" covalent bonds. This model was the stimulus behind his famous 1973 paper The Strength of the Weak Tie, which is now considered a classic paper in sociology. Thus, weak social ties, or weak ties, it is argued, are responsible for the majority of the embeddedness and structure of social networks in society as well as the transmission of information through these networks. Specifically, more novel information flows to individuals through weak than through strong ties. Because our close friends tend to move in the same circles that we do, the information they receive overlaps considerably with what we already know. Acquaintances, by contrast, know people that we do not, and thus receive more novel information.[31] ## Limerent bond According to limerence theory, positioned in 1979 by psychologist Dorothy Tennov, a certain percentage of couples may go through what is called a limerent reaction, in which one or both of the pair may experience a state of passion mixed with continuous intrusive thinking, fear of rejection, and hope. Hence, with all human romantic relationships, one of three varieties of bonds may form, defined over a set duration of time, in relation to the experience or non-experience of limerence: - Affectional bond: define relationships in which neither partner is limerent. - Limerent-Nonlimerent bond: define relationships in which one partner is limerent. - Limerent-Limerent bond: define relationships in which both partners are limerent. The constitution of these bonds may vary over the course of the relationship, in ways that may either increase or decrease the intensity of the limerence. The basis and interesting characteristic of this delineation made by Tennov, is that based on her research and interviews with over 500 people, all human bonded relationships can be divided into three varieties being defined by the amount of limerence or non-limerence each partner contributes to the relationship. ## Erotic bond In the 1988 book Love Maps psychologist John Money postulated the existence of the erotic bond. According to Money, each person is theorized to have a correlative love map based on his or her upbringing and experiences.[32] This concept is frequently referenced in interpersonal-relationship discussions. A love map may make note of both positive and negative factors, things that attract or repel the person whose erotic tastes are being mapped. For reasons that are not always easy to understand, one person may be attracted to people of a particular gender, people with particular physical characteristics (such as hair color), people with particular personality traits (e.g., a sardonic sense of humor), and so forth. One may also find certain characteristics so threatening or objectionable (again, for reasons that may be difficult or impossible to ascertain) that it strongly mitigates against an erotic attraction being manifested. Using this love map, a person unconsciously makes note of the personal and environmental factors that facilitate the formation of an erotic bond.[32] ## Limbic bond In 2000, psychologists Lewis, Amini, and Lannon published their famous A General Theory of Love in which they postulated the concept of the limbic bond, which defines a bodily connection that is limbic in nature. They also refer to this bond as a mammalian bond being that mammals in contrast to reptiles have a limbic system, which is why reptiles abandon their young after birth whereas mammals do not. In the limbic bond, a mutually synchronizing sensory exchange as bodily warmth, olfactory cues, vocal exchange, visual interactions, etc., function to keep ties or organizing sensory channels between connected individuals. These ties or bonds function to regulate those associated persons. They define this design as an open-loop regulatory system; where, as they state, adults are social animals: they continue to require a source of stabilization outside themselves. The open loop design means that in some important ways, people cannot be stable on their own; stability means finding people who regulate you well and staying near them.[33] ## Societal bond The societal bond refers to those cohesive elements and structural ties, as economic activity, unions, trade, sanctions, etc., which function to bind societies into collective units. According to encyclopedia.com, marriage functions to cement the societal bond. As they state, in many societies marriage links not just nuclear families but larger social formations as well. Some endogamous societies are divided into exogamous groups, as clans or lineages. Here, men form alliances through exchange of women, and the social organization regulates these alliances through marriage rules.[34] ## Human-animal bond The human-animal bond can be defined as a connection between people and animals, domestic or wild; be it a cat as a pet or birds outside one’s window. Research into the nature and merit of the human animal bond began in the late 1700s when, in York, England, the Society of Friends established the The Retreat to provide humane treatment for the mentally ill. By having patients care for the many farm animals on the estate, society officials theorized that the combination of animal contact plus productive work would facilitate the patients’ rehabilitation. In the 1870s in Paris, a French surgeon had patients with neurological disorders ride horses. The patients were found to have improved their motor control and balance and were less likely to suffer bouts of depression.[35] In the 19th century, in Bielefeld, Germany, epileptic patients were given the prescription to spend time each day taking care of cats and dogs. The contact with the animals was found to reduce the occurrence of seizures. In 1980, a team of scientists at the University of Pennsylvania found that human to animal contact was found to reduce the physiological characteristics of stress; specifically, lowered levels of blood pressure, heart rate, respiratory rate, anxiety, and tension were all found to correlate positively with human pet bonding.[35] Historically, animals were domesticated for functional use; for example, dogs for herding and tracking, and cats for killing mice or rats. Today, in Western societies, their function is primarily a bonding function. For example, current studies show that 60-80% of dogs sleep with their owners at night in the bedroom, either in or on the bed.[36] Moreover, in the past the majority of cats were kept outside (barn cats) whereas today most cats are kept indoors (housecats) and considered part of the family. Presently, in the US, for example, 1.2 billion animals are kept as pets, primarily for bonding purposes.[36] In addition, as of 1995 there were over 30 research institutions looking into the potential benefits of the human animal bond.[35] # Debonding In 1976, sociologist Diane Vaughan proposed an “uncoupling theory”, where, during the dynamics of relationship breakup, there exists "turning point", only noted in hindsight, followed by transition period in which one partner unconsciously knows the relationship is going to end, but holds on to it for an extended period, sometimes for a number of years.[13]	https://www.wikidoc.org/index.php/Human_bonding
67c64796f5a2409468537c898c28b7b949f39ac7	wikidoc	Hungarian Oak	Hungarian Oak The Hungarian Oak or Italian Oak (Quercus frainetto; syn. Quercus conferta Kit., Quercus farnetto Ten.) is a species of oak, native to southeastern Europe (parts of Italy, the Balkans, parts of Hungary, Romania) and Turkey; it is classified in Quercus sect. Mesobalanus. It is a large deciduous tree, reaching heights of 38 m and a trunk diameter of nearly 2 m. The leaves are large, 14-25 cm long (occasionally up to 33 cm), variable in shape, divided into 6-10 very deep parallel lobes which are usually divided into sublobes. The leaf stalks are usually short, 2-6 mm (rarely to 22 mm) long. The leaves are widest close to the apex, which is broad and short pointed. The base of the leaf usually has ear shaped projections (auricles) which sometimes overlap the twig. The light yellow green expanding leaves turn rich dark green by the beginning of summer. The leaves are covered with minute russet hairs, especially the lower surface. The leaves are concentrated at the ends of twigs. The leaves turn brown, russet or yellow in fall and sometimes remain attached to the twigs until the following spring. The buds are large, long and pointed, shiny russet or light brown in colour with minute tomentum. The twigs are stout and covered with russet upward pointed hairs. The light brown acorns mature in about 6 months. They are 15-35 mm long, egg shaped, usually with a blunt apex. The acorn cup is covered with long overlapping scales and russet hairs. The acorns tend to concentrate in groups of two to eight at the ends of twigs. The centre of the Hungarian Oak native range is in the Balkans. It is adapted to the subcontinental climate of southeastern Europe but the main factor of its occurrence at a particular site is the soil. It is specially adapted to heavy acidic soils (cambisols and vertisols), typical of Serbia, Bulgaria and Romania. These soils are usually leached out, very dry in the summer and sometimes waterlogged in the spring. However, the Hungarian Oak does not tolerate flooding or high water tables. It is also extremely sensitive to the presence of lime in the soil. Hence, opposite to its English name, the Hungarian Oak is a very rare tree in Hungary, where the soils are generally very rich in lime. The Hungarian Oak-Turkey Oak forest (Quercetum frainetto-cerris Rud.) is the most widespread association of this oak in the Balkans, which is also the most common forest type in Serbia. # Cultivation It is an outstanding ornamental tree for large gardens.	Hungarian Oak The Hungarian Oak or Italian Oak (Quercus frainetto; syn. Quercus conferta Kit., Quercus farnetto Ten.) is a species of oak, native to southeastern Europe (parts of Italy, the Balkans, parts of Hungary, Romania) and Turkey; it is classified in Quercus sect. Mesobalanus. It is a large deciduous tree, reaching heights of 38 m and a trunk diameter of nearly 2 m. The leaves are large, 14-25 cm long (occasionally up to 33 cm), variable in shape, divided into 6-10 very deep parallel lobes which are usually divided into sublobes. The leaf stalks are usually short, 2-6 mm (rarely to 22 mm) long. The leaves are widest close to the apex, which is broad and short pointed. The base of the leaf usually has ear shaped projections (auricles) which sometimes overlap the twig. The light yellow green expanding leaves turn rich dark green by the beginning of summer. The leaves are covered with minute russet hairs, especially the lower surface. The leaves are concentrated at the ends of twigs. The leaves turn brown, russet or yellow in fall and sometimes remain attached to the twigs until the following spring. The buds are large, long and pointed, shiny russet or light brown in colour with minute tomentum. The twigs are stout and covered with russet upward pointed hairs. The light brown acorns mature in about 6 months. They are 15-35 mm long, egg shaped, usually with a blunt apex. The acorn cup is covered with long overlapping scales and russet hairs. The acorns tend to concentrate in groups of two to eight at the ends of twigs. The centre of the Hungarian Oak native range is in the Balkans. It is adapted to the subcontinental climate of southeastern Europe but the main factor of its occurrence at a particular site is the soil. It is specially adapted to heavy acidic soils (cambisols and vertisols), typical of Serbia, Bulgaria and Romania. These soils are usually leached out, very dry in the summer and sometimes waterlogged in the spring. However, the Hungarian Oak does not tolerate flooding or high water tables. It is also extremely sensitive to the presence of lime in the soil. Hence, opposite to its English name, the Hungarian Oak is a very rare tree in Hungary, where the soils are generally very rich in lime. The Hungarian Oak-Turkey Oak forest (Quercetum frainetto-cerris Rud.) is the most widespread association of this oak in the Balkans, which is also the most common forest type in Serbia. ## Cultivation It is an outstanding ornamental tree for large gardens.	https://www.wikidoc.org/index.php/Hungarian_Oak
6d3b53be233fa63d85ad29ce0b105cca62c7e9a5	wikidoc	Hurthle cells	Hurthle cells # Overview Hurthle cells are also called Askanazy cells. They are the specific cells found in the thyroid gland and are visible on the histopathological picture. Hurthle cells have eosinophilic cytoplasm and are abundant in mitochondria. They may be present in a variety of thyroid diseases including Hashimoto's thyroiditis and thyroid carcinoma (Hürthle cel carcinoma; A subtype of follicular thyroid cancer). # Hurthle cells Hurthle cells are also called Askanazy cells. They are the specific cells found in the thyroid gland and are visible on the histopathological picture. Hurthle cells have eosinophilic cytoplasm and are abundant in mitochondria. They may be present in a variety of thyroid diseases including Hashimoto's thyroiditis and thyroid carcinoma (Hürthle cel carcinoma; A subtype of follicular thyroid cancer). ## History The Hürthle cell is named after German histologist Karl Hürthle, who investigated thyroid secretory function, particularly in dogs. The cell known as the Hürthle cell was first described in 1898 by Max Askanazy, who noted it in patients with Graves' disease. Oncocytes in the thyroid are often called Hürthle cells. Although the terms oncocyte, oxyphilic cell, and Hürthle cell are used interchangeably, Hürthle cell is used only to indicate cells of thyroid follicular origin. ## Microscopic Histology Hurthle cells are also called Askanazy cells. They are the specific cells found in the thyroid gland and are visible on the histopathological picture. They may be present in a variety of thyroid diseases including Hashimoto's thyroiditis and thyroid carcinoma. These cells are characterized by the following: - Large, polygonal cells - Eosinophilic cytoplasm - Abundance of mitochondria ## Significance of Hurthle cells Hurthle cells are present in the following conditions: - Hashimoto's thyroiditis - Grave's disease - Benign thyroid adenomas - Follicular thyroid carcinoma ## Diagnosis Hürthle cell adenomas are more frequent than Hürthle cell carcinomas. It is difficult to differentiate between being benign or malignant Hürthle cell lesions. Chronic lymphocytic thyroiditis or Hashimoto's thyroiditis, along with cases of long-standing Graves' disease, show Hürthle cells present. Classification is important since widely invasive tumors can have outcomes with a 55% mortality rate. Hürthle cell carcinomas consist of at least 75% Hürthle cells. - Size and growth pattern of the tumor cannot be used to determine malignancy, although larger tumors have a higher incidence of malignancy, Hürthle cell adenomas and carcinomas are differentiated on the basis of capsular and vascular invasion. - Tumors displaying only capsular invasion tend to behave less aggressively than those with vascular invasion. - Hürthle cell carcinomas are characterized as either minimally invasive or widely invasive tumors. - The minimally invasive or encapsulated carcinoma is fully surrounded by a fibrous capsule. - The widely invasive carcinoma shows an extensive area of both capsular and vascular invasion with the leftover capsule typically difficult to identify. ## Treatment The appropriate diagnosis of the underlying cause of the Hurthle cells in the histological picture directs the treatment. - Grave's disease and Hashimoto's thyroiditis are usually treated for hyperthyroidism and hypothyroidism respectively. - A non-minimally invasive Hürthle cell carcinoma is typically treated by a total thyroidectomy followed by radioactive iodine therapy. - A Hürthle cell adenoma or a minimally invasive tumor can be treated by a thyroid lobectomy, although some surgeons will perform a total thyroidectomy to prevent the tumor from reappearing and metastasizing.	Hurthle cells Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Furqan M M. M.B.B.S[2] # Overview Hurthle cells are also called Askanazy cells. They are the specific cells found in the thyroid gland and are visible on the histopathological picture. Hurthle cells have eosinophilic cytoplasm and are abundant in mitochondria. They may be present in a variety of thyroid diseases including Hashimoto's thyroiditis and thyroid carcinoma (Hürthle cel carcinoma; A subtype of follicular thyroid cancer). # Hurthle cells Hurthle cells are also called Askanazy cells. They are the specific cells found in the thyroid gland and are visible on the histopathological picture. Hurthle cells have eosinophilic cytoplasm and are abundant in mitochondria. They may be present in a variety of thyroid diseases including Hashimoto's thyroiditis and thyroid carcinoma (Hürthle cel carcinoma; A subtype of follicular thyroid cancer). ## History The Hürthle cell is named after German histologist Karl Hürthle, who investigated thyroid secretory function, particularly in dogs. The cell known as the Hürthle cell was first described in 1898 by Max Askanazy, who noted it in patients with Graves' disease. Oncocytes in the thyroid are often called Hürthle cells. Although the terms oncocyte, oxyphilic cell, and Hürthle cell are used interchangeably, Hürthle cell is used only to indicate cells of thyroid follicular origin.[1][2][3][4] ## Microscopic Histology Hurthle cells are also called Askanazy cells. They are the specific cells found in the thyroid gland and are visible on the histopathological picture. They may be present in a variety of thyroid diseases including Hashimoto's thyroiditis and thyroid carcinoma.[5][6][7] These cells are characterized by the following: - Large, polygonal cells - Eosinophilic cytoplasm - Abundance of mitochondria ## Significance of Hurthle cells Hurthle cells are present in the following conditions:[7] - Hashimoto's thyroiditis - Grave's disease - Benign thyroid adenomas - Follicular thyroid carcinoma ## Diagnosis Hürthle cell adenomas are more frequent than Hürthle cell carcinomas. It is difficult to differentiate between being benign or malignant Hürthle cell lesions. Chronic lymphocytic thyroiditis or Hashimoto's thyroiditis, along with cases of long-standing Graves' disease, show Hürthle cells present. Classification is important since widely invasive tumors can have outcomes with a 55% mortality rate. Hürthle cell carcinomas consist of at least 75% Hürthle cells.[5][6][10] - Size and growth pattern of the tumor cannot be used to determine malignancy, although larger tumors have a higher incidence of malignancy, Hürthle cell adenomas and carcinomas are differentiated on the basis of capsular and vascular invasion. - Tumors displaying only capsular invasion tend to behave less aggressively than those with vascular invasion. - Hürthle cell carcinomas are characterized as either minimally invasive or widely invasive tumors. - The minimally invasive or encapsulated carcinoma is fully surrounded by a fibrous capsule. - The widely invasive carcinoma shows an extensive area of both capsular and vascular invasion with the leftover capsule typically difficult to identify. ## Treatment The appropriate diagnosis of the underlying cause of the Hurthle cells in the histological picture directs the treatment.[5] - Grave's disease and Hashimoto's thyroiditis are usually treated for hyperthyroidism and hypothyroidism respectively. - A non-minimally invasive Hürthle cell carcinoma is typically treated by a total thyroidectomy followed by radioactive iodine therapy. - A Hürthle cell adenoma or a minimally invasive tumor can be treated by a thyroid lobectomy, although some surgeons will perform a total thyroidectomy to prevent the tumor from reappearing and metastasizing.	https://www.wikidoc.org/index.php/Hurthle_cells
dfcd7df54b576bca0b00d6e1ab3526e806066de9	wikidoc	Hyacinth bean	Hyacinth bean The Hyacinth Bean (Lablab purpureus, syn. Dolichos lablab L., Dolichos purpureus L., Lablab niger Medikus, Lablab lablab (L.) Lyons, Vigna aristata Piper, and Lablab vulgaris, L.) Savi. ), also called Indian Bean and Egyptian Bean, is a species of bean in the family Fabaceae that is widespread as a food crop throughout the tropics, especially in Africa. The hyacinth bean grows as a vine, producing purple flowers and striking electric-purple coloured seed pods. Pods and seeds may be poisonous due to high concentrations of cyanogenic glucosides, and can only be eaten after prolonged boiling. It is also grown as forage and as an ornamental plant. In addition, this plant is also cited as a medicinal plant and a poisonous plant.	Hyacinth bean The Hyacinth Bean (Lablab purpureus, syn. Dolichos lablab L., Dolichos purpureus L., Lablab niger Medikus, Lablab lablab (L.) Lyons, Vigna aristata Piper, and Lablab vulgaris, L.) Savi. [1]), also called Indian Bean and Egyptian Bean, is a species of bean in the family Fabaceae that is widespread as a food crop throughout the tropics, especially in Africa. The hyacinth bean grows as a vine, producing purple flowers and striking electric-purple coloured seed pods. Pods and seeds may be poisonous due to high concentrations of cyanogenic glucosides, and can only be eaten after prolonged boiling. It is also grown as forage [2] and as an ornamental plant. [3] In addition, this plant is also cited as a medicinal plant and a poisonous plant. [4] [5] # External links - The Hyacinth Bean - Informative but non-scholarly essay on Hyacinth Bean history, uses, etymology. - The Banglalore bean - Murphy, Andrea M.; Colucci, Pablo E. A tropical forage solution to poor quality ruminant diets: A review of Lablab purpureus Livestock Research for Rural Development (11) 2 1999 - Nutrition facts	https://www.wikidoc.org/index.php/Hyacinth_bean
51b11a6b0b3d0628fc96a445bed43a2b9d18ee02	wikidoc	Hydra viridis	Hydra viridis Hydra viridis (also known as Chlorohydra viridis) is a species of hydra found widely dispersed in the northern temperate zone. It is a common organisms found in still waters from early spring to late autumn. The characteristic green colour comes from cells of the unicellular alga Chlorella within the cells of the gastrodermis. Because of this, they are generally less predacious than aposymbiotic hydra species . It is most commonly found attached to the stems of water plants and the undersides of leaves including duckweed. When disturbed it retracts to a small green blob which is easily overlooked. Gently sweeping through a clean weedy pond and allowing the collected water and leaves to stand in a jar will often reveal Hydra virdis emerging after only a few minutes. H. viridis in captivity will tend to congregate towards the light. When in feeding mode, the extended tentacles are generally only as long as, or shorter than the body.	Hydra viridis Hydra viridis (also known as Chlorohydra viridis) is a species of hydra found widely dispersed in the northern temperate zone. It is a common organisms found in still waters from early spring to late autumn. The characteristic green colour comes from cells of the unicellular alga Chlorella within the cells of the gastrodermis. Because of this, they are generally less predacious than aposymbiotic hydra species [1]. It is most commonly found attached to the stems of water plants and the undersides of leaves including duckweed. When disturbed it retracts to a small green blob which is easily overlooked. Gently sweeping through a clean weedy pond and allowing the collected water and leaves to stand in a jar will often reveal Hydra virdis emerging after only a few minutes. H. viridis in captivity will tend to congregate towards the light. When in feeding mode, the extended tentacles are generally only as long as, or shorter than the body.	https://www.wikidoc.org/index.php/Hydra_viridis
20c158704e9089e72037c1775dc0bc0449e26c55	wikidoc	Hydrochloride	Hydrochloride # Overview In chemistry, hydrochlorides are salts resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base (mostly amines). This is also known as muriate, derived from hydrochloric acid's other name: muriatic acid. For example, reaction of pyridine (C5H5N) with hydrochloric acid (HCl) yields pyridine hydrochloride (C5H5N·HCl). Even though this style of formulas is often used for denoting the hydrochlorides, the dot incorrectly implies that the two molecules are weakly bonded together. It is the salt C5H5NH+ Cl- with correct chemical name pyridinium chloride. # Uses Converting otherwise insoluble amines into their hydrochlorides is a common way to make them water- and acid-soluble. This is particularly desirable for substances used in medications. Many pharmaceutical substances used are prepared as hydrochlorides so that they may be quickly absorbed in the gastrointestinal tract. The typical breadth of time needed for a hydrochloride to be absorbed thusly is 15-30 minutes. Examples of hydrochlorides in medical uses are many, ranging from over-the-counter sinus relief to antinausea medication used mainly in the pre-treatment of chemotherapy-induced nausea and vomiting (Zofran, Ondansetron hydrochloride). de:Hydrochlorid nl:Waterstofchloride	Hydrochloride # Overview In chemistry, hydrochlorides are salts resulting, or regarded as resulting, from the reaction of hydrochloric acid with an organic base (mostly amines). This is also known as muriate, derived from hydrochloric acid's other name: muriatic acid. For example, reaction of pyridine (C5H5N) with hydrochloric acid (HCl) yields pyridine hydrochloride (C5H5N·HCl). Even though this style of formulas is often used for denoting the hydrochlorides, the dot incorrectly implies that the two molecules are weakly bonded together. It is the salt C5H5NH+ Cl- with correct chemical name pyridinium chloride. # Uses Converting otherwise insoluble amines into their hydrochlorides is a common way to make them water- and acid-soluble. This is particularly desirable for substances used in medications. Many pharmaceutical substances used are prepared as hydrochlorides so that they may be quickly absorbed in the gastrointestinal tract. The typical breadth of time needed for a hydrochloride to be absorbed thusly is 15-30 minutes. Examples of hydrochlorides in medical uses are many, ranging from over-the-counter sinus relief to antinausea medication used mainly in the pre-treatment of chemotherapy-induced nausea and vomiting (Zofran, Ondansetron hydrochloride). Template:WH Template:WikiDoc Sources de:Hydrochlorid nl:Waterstofchloride	https://www.wikidoc.org/index.php/Hydrochloride
5d154f9dc803375dfc389f9799eb53d7d8bf4488	wikidoc	Hydrogen atom	Hydrogen atom A hydrogen atom is an atom of the chemical element hydrogen. The electrically neutral atom contains a single positively-charged proton and a single negatively-charged electron bound to the nucleus by the Coulomb force. The most abundant isotope, hydrogen-1, protium, or light hydrogen, contains no neutrons; other isotopes contain one or more neutrons. This article primarily concerns hydrogen-1. The hydrogen atom has special significance in quantum mechanics and quantum field theory as a simple two-body problem physical system which has yielded many simple analytical solutions in closed-form. In 1913, Niels Bohr obtained the spectral frequencies of the hydrogen atom after making a number of simplifying assumptions. These assumptions, the cornerstones of the Bohr model, were not fully correct but did yield the correct energy answers. Bohr's results for the frequencies and underlying energy values were confirmed by the full quantum-mechanical analysis which uses the Schrödinger equation, as was shown in 1925/26. The solution to the Schrödinger equation for hydrogen is analytical. From this, the hydrogen energy levels and thus the frequencies of the hydrogen spectral lines can be calculated. The solution of the Schrödinger equation goes much further than the Bohr model however, because it also yields the shape of the electron's wave function ("orbital") for the various possible quantum-mechanical states, thus explaining the anisotropic character of atomic bonds. The Schrödinger equation also applies to more complicated atoms and molecules. However, in most such cases the solution is not analytical and either computer calculations are necessary or simplifying assumptions must be made. # Solution of Schrödinger equation: Overview of results The solution of the Schrödinger equation (wave equations) for the hydrogen atom uses the fact that the Coulomb potential produced by the nucleus is isotropic (it is radially symmetric in space and only depends on the distance to the nucleus). Although the resulting energy eigenfunctions (the "orbitals") are not necessarily isotropic themselves, their dependence on the angular coordinates follows completely generally from this isotropy of the underlying potential: The eigenstates of the Hamiltonian (= energy eigenstates) can be chosen as simultaneous eigenstates of the angular momentum operator. This corresponds to the fact that angular momentum is conserved in the orbital motion of the electron around the nucleus. Therefore, the energy eigenstates may be classified by two angular momentum quantum numbers, l and m (integer numbers). The "angular momentum" quantum number l = 0, 1, 2, ... determines the magnitude of the angular momentum. The "magnetic" quantum number m = −l, .., +l determines the projection of the angular momentum on the (arbitrarily chosen) z-axis. In addition to mathematical expressions for total angular momentum and angular momentum projection of wavefunctions, an expression for the radial dependence of the wave functions must be found. It is only here that the details of the 1/r Coulomb potential enter (leading to Laguerre polynomials in r). This leads to a third quantum number, the principal quantum number n = 1, 2, 3, ... The principal quantum number in hydrogen is related to atom's total energy. Note that the maximum value of the angular momentum quantum number is limited by the principal quantum number: it can run only up to n − 1, i.e. l = 0, 1, ..., n − 1. Due to angular momentum conservation, states of the same l but different m have the same energy (this holds for all problems with rotational symmetry). In addition, for the hydrogen atom, states of the same n but different l are also degenerate (i.e. they have the same energy). However, this is a specific property of hydrogen and is no longer true for more complicated atoms which have a (effective) potential differing from the form 1/r (due to the presence of the inner electrons shielding the nucleus potential). Taking into account the spin of the electron adds a last quantum number, the projection of the electron's spin angular momentum along the z axis, which can take on two values. Therefore, any eigenstate of the electron in the hydrogen atom is described fully by four quantum numbers. According to the usual rules of quantum mechanics, the actual state of the electron may be any superposition of these states. This explains also why the choice of z-axis for the directional quantization of the angular momentum vector is immaterial: An orbital of given l and m' obtained for another preferred axis z' can always be represented as a suitable superposition of the various states of different m (but same l) that have been obtained for z. # Mathematical summary of eigenstates of hydrogen atom ## Energy levels The energy levels of hydrogen, including fine structure are given by The value of -13.6 eV can be found from the simple Bohr model, and is related to the mass, m, and charge of the electron, q: It is even more elegantly connected to fine-structure constant: ## Wavefunction The normalized position wavefunctions, given in spherical coordinates are: where: ## Angular momentum The eigenvalues for Angular momentum operator: # Visualizing the hydrogen electron orbitals The image to the right shows the first few hydrogen atom orbitals (energy eigenfunctions). These are cross-sections of the probability density that are color-coded (black=zero density, white=highest density). The angular momentum quantum number l is denoted in each column, using the usual spectroscopic letter code ("s" means l = 0; "p": l = 1; "d": l = 2). The main quantum number n (= 1, 2, 3, ...) is marked to the right of each row. For all pictures the magnetic quantum number m has been set to 0, and the cross-sectional plane is the xz-plane (z is the vertical axis). The probability density in three-dimensional space is obtained by rotating the one shown here around the z-axis. The "ground state", i.e. the state of lowest energy, in which the electron is usually found, is the first one, the "1s" state (principal quantum level n = 1, l = 0). An image with more orbitals is also available (up to higher numbers n and l). Note the number of black lines that occur in each but the first orbital. These are "nodal lines" (which are actually nodal surfaces in three dimensions). Their total number is always equal to n − 1, which is the sum of the number of radial nodes (equal to n - l - 1) and the number of angular nodes (equal to l). # Features going beyond the Schrödinger solution There are several important effects that are neglected by the Schrödinger equation and which are responsible for certain small but measurable deviations of the real spectral lines from the predicted ones: - Although the mean speed of the electron in hydrogen is only 1/137th of the speed of light, there is an increase in the electron's mass as predicted by special relativity. Its mass and momentum increase by about one part in 37,000. Since the electron's wavelength is determined by its momentum, orbitals containing higher speed electrons show contraction due to smaller wavelengths. For elements with high atomic number Z, this effect is more pronounced, and especially so for s electrons, which move at relativistic velocities as they penetrate the screening electrons near the core of high Z atoms. This relativistic mass effect for electrons causes a contraction of 6s orbitals relative to 5d orbitals (by comparison to corresponding s and d electrons in lighter elements in the same column of the periodic table); this results in 6s valence electrons becoming lowered in energy. Examples of significant physical outcomes of this effect include the lowered melting temperature of mercury (which results from 6s electrons not being available for metal bonding) and the golden color of gold and caesium (which result from narrowing of 6s to 5d transition energy to the point that visible light begins to be absorbed). See and ). - Even when there is no external magnetic field, in the inertial frame of the moving electron, the electromagnetic field of the nucleus has a magnetic component. The spin of the electron has an associated magnetic moment which interacts with this magnetic field. This effect is also explained by special relativity, and it leads to the so-called spin-orbit coupling, i.e., an interaction between the electron's orbital motion around the nucleus, and its spin. Both of these features (and more) are incorporated in the relativistic Dirac equation, with predictions that come still closer to experiment. Again the Dirac equation may be solved analytically in the special case of a two-body system, such as the hydrogen atom. The resulting solution quantum states now must be classified by the total angular momentum number j (arising through the coupling between electron spin and orbital angular momentum). States of the same j and the same n are still degenerate. - There are always vacuum fluctuations of the electromagnetic field, according to quantum mechanics. Due to such fluctuations degeneracy between states of the same j but different l is lifted, giving them slightly different energies. This has been demonstrated in the famous Lamb-Retherford experiment and was the starting point for the development of the theory of Quantum electrodynamics (which is able to deal with these vacuum fluctuations and employs the famous Feynman diagrams for approximations using perturbation theory). This effect is now called Lamb shift. For these developments, it was essential that the solution of the Dirac equation for the hydrogen atom could be worked out exactly, such that any experimentally observed deviation had to be taken seriously as a signal of failure of the theory. Due to the high precision of the theory also very high precision for the experiments is needed, which utilize a frequency comb.	Hydrogen atom Template:Otheruses4 Template:Tfd A hydrogen atom is an atom of the chemical element hydrogen. The electrically neutral atom contains a single positively-charged proton and a single negatively-charged electron bound to the nucleus by the Coulomb force. The most abundant isotope, hydrogen-1, protium, or light hydrogen, contains no neutrons; other isotopes contain one or more neutrons. This article primarily concerns hydrogen-1. The hydrogen atom has special significance in quantum mechanics and quantum field theory as a simple two-body problem physical system which has yielded many simple analytical solutions in closed-form. In 1913, Niels Bohr obtained the spectral frequencies of the hydrogen atom after making a number of simplifying assumptions. These assumptions, the cornerstones of the Bohr model, were not fully correct but did yield the correct energy answers. Bohr's results for the frequencies and underlying energy values were confirmed by the full quantum-mechanical analysis which uses the Schrödinger equation, as was shown in 1925/26. The solution to the Schrödinger equation for hydrogen is analytical. From this, the hydrogen energy levels and thus the frequencies of the hydrogen spectral lines can be calculated. The solution of the Schrödinger equation goes much further than the Bohr model however, because it also yields the shape of the electron's wave function ("orbital") for the various possible quantum-mechanical states, thus explaining the anisotropic character of atomic bonds. The Schrödinger equation also applies to more complicated atoms and molecules. However, in most such cases the solution is not analytical and either computer calculations are necessary or simplifying assumptions must be made. # Solution of Schrödinger equation: Overview of results The solution of the Schrödinger equation (wave equations) for the hydrogen atom uses the fact that the Coulomb potential produced by the nucleus is isotropic (it is radially symmetric in space and only depends on the distance to the nucleus). Although the resulting energy eigenfunctions (the "orbitals") are not necessarily isotropic themselves, their dependence on the angular coordinates follows completely generally from this isotropy of the underlying potential: The eigenstates of the Hamiltonian (= energy eigenstates) can be chosen as simultaneous eigenstates of the angular momentum operator. This corresponds to the fact that angular momentum is conserved in the orbital motion of the electron around the nucleus. Therefore, the energy eigenstates may be classified by two angular momentum quantum numbers, l and m (integer numbers). The "angular momentum" quantum number l = 0, 1, 2, ... determines the magnitude of the angular momentum. The "magnetic" quantum number m = −l, .., +l determines the projection of the angular momentum on the (arbitrarily chosen) z-axis. In addition to mathematical expressions for total angular momentum and angular momentum projection of wavefunctions, an expression for the radial dependence of the wave functions must be found. It is only here that the details of the 1/r Coulomb potential enter (leading to Laguerre polynomials in r). This leads to a third quantum number, the principal quantum number n = 1, 2, 3, ... The principal quantum number in hydrogen is related to atom's total energy. Note that the maximum value of the angular momentum quantum number is limited by the principal quantum number: it can run only up to n − 1, i.e. l = 0, 1, ..., n − 1. Due to angular momentum conservation, states of the same l but different m have the same energy (this holds for all problems with rotational symmetry). In addition, for the hydrogen atom, states of the same n but different l are also degenerate (i.e. they have the same energy). However, this is a specific property of hydrogen and is no longer true for more complicated atoms which have a (effective) potential differing from the form 1/r (due to the presence of the inner electrons shielding the nucleus potential). Taking into account the spin of the electron adds a last quantum number, the projection of the electron's spin angular momentum along the z axis, which can take on two values. Therefore, any eigenstate of the electron in the hydrogen atom is described fully by four quantum numbers. According to the usual rules of quantum mechanics, the actual state of the electron may be any superposition of these states. This explains also why the choice of z-axis for the directional quantization of the angular momentum vector is immaterial: An orbital of given l and m' obtained for another preferred axis z' can always be represented as a suitable superposition of the various states of different m (but same l) that have been obtained for z. # Mathematical summary of eigenstates of hydrogen atom ## Energy levels The energy levels of hydrogen, including fine structure are given by The value of -13.6 eV can be found from the simple Bohr model, and is related to the mass, m, and charge of the electron, q: It is even more elegantly connected to fine-structure constant: ## Wavefunction The normalized position wavefunctions, given in spherical coordinates are: where: ## Angular momentum The eigenvalues for Angular momentum operator: # Visualizing the hydrogen electron orbitals The image to the right shows the first few hydrogen atom orbitals (energy eigenfunctions). These are cross-sections of the probability density that are color-coded (black=zero density, white=highest density). The angular momentum quantum number l is denoted in each column, using the usual spectroscopic letter code ("s" means l = 0; "p": l = 1; "d": l = 2). The main quantum number n (= 1, 2, 3, ...) is marked to the right of each row. For all pictures the magnetic quantum number m has been set to 0, and the cross-sectional plane is the xz-plane (z is the vertical axis). The probability density in three-dimensional space is obtained by rotating the one shown here around the z-axis. The "ground state", i.e. the state of lowest energy, in which the electron is usually found, is the first one, the "1s" state (principal quantum level n = 1, l = 0). An image with more orbitals is also available (up to higher numbers n and l). Note the number of black lines that occur in each but the first orbital. These are "nodal lines" (which are actually nodal surfaces in three dimensions). Their total number is always equal to n − 1, which is the sum of the number of radial nodes (equal to n - l - 1) and the number of angular nodes (equal to l). # Features going beyond the Schrödinger solution There are several important effects that are neglected by the Schrödinger equation and which are responsible for certain small but measurable deviations of the real spectral lines from the predicted ones: - Although the mean speed of the electron in hydrogen is only 1/137th of the speed of light, there is an increase in the electron's mass as predicted by special relativity. Its mass and momentum increase by about one part in 37,000. Since the electron's wavelength is determined by its momentum, orbitals containing higher speed electrons show contraction due to smaller wavelengths. For elements with high atomic number Z, this effect is more pronounced, and especially so for s electrons, which move at relativistic velocities as they penetrate the screening electrons near the core of high Z atoms. This relativistic mass effect for electrons causes a contraction of 6s orbitals relative to 5d orbitals (by comparison to corresponding s and d electrons in lighter elements in the same column of the periodic table); this results in 6s valence electrons becoming lowered in energy. Examples of significant physical outcomes of this effect include the lowered melting temperature of mercury (which results from 6s electrons not being available for metal bonding) and the golden color of gold and caesium (which result from narrowing of 6s to 5d transition energy to the point that visible light begins to be absorbed). See [1] and [2]). - Even when there is no external magnetic field, in the inertial frame of the moving electron, the electromagnetic field of the nucleus has a magnetic component. The spin of the electron has an associated magnetic moment which interacts with this magnetic field. This effect is also explained by special relativity, and it leads to the so-called spin-orbit coupling, i.e., an interaction between the electron's orbital motion around the nucleus, and its spin. Both of these features (and more) are incorporated in the relativistic Dirac equation, with predictions that come still closer to experiment. Again the Dirac equation may be solved analytically in the special case of a two-body system, such as the hydrogen atom. The resulting solution quantum states now must be classified by the total angular momentum number j (arising through the coupling between electron spin and orbital angular momentum). States of the same j and the same n are still degenerate. - There are always vacuum fluctuations of the electromagnetic field, according to quantum mechanics. Due to such fluctuations degeneracy between states of the same j but different l is lifted, giving them slightly different energies. This has been demonstrated in the famous Lamb-Retherford experiment and was the starting point for the development of the theory of Quantum electrodynamics (which is able to deal with these vacuum fluctuations and employs the famous Feynman diagrams for approximations using perturbation theory). This effect is now called Lamb shift. For these developments, it was essential that the solution of the Dirac equation for the hydrogen atom could be worked out exactly, such that any experimentally observed deviation had to be taken seriously as a signal of failure of the theory. Due to the high precision of the theory also very high precision for the experiments is needed, which utilize a frequency comb.	https://www.wikidoc.org/index.php/Hydrogen-1
d8ab431cc08fa21f65aef56a42492c34e4349e1b	wikidoc	Hydrogen bond	Hydrogen bond A hydrogen bond is a special type of dipole-dipole force that exists between an electronegative atom and a hydrogen atom bonded to another electronegative atom. This type of force always involves a hydrogen atom and the energy of this attraction is close to that of weak covalent bonds (155 kJ/mol), thus the name - Hydrogen Bonding. These attractions can occur between molecules (intermolecularly), or within different parts of a single molecule (intramolecularly). The hydrogen bond is a very strong fixed dipole-dipole van der Waals-Keesom force, but weaker than covalent, ionic and metallic bonds. The hydrogen bond is somewhere between a covalent bond and an electrostatic intermolecular attraction. Intermolecular hydrogen bonding is responsible for the high boiling point of water (100 °C). This is because of the strong hydrogen bond, as opposed to other group 16 hydrides. Intramolecular hydrogen bonding is partly responsible for the secondary, tertiary, and quaternary structures of proteins and nucleic acids. # Bonding A hydrogen atom attached to a relatively electronegative atom is a hydrogen bond donor. This electronegative atom is usually fluorine, oxygen, or nitrogen. An electronegative atom such as fluorine, oxygen, or nitrogen is a hydrogen bond acceptor, regardless of whether it is bonded to a hydrogen atom or not. An example of a hydrogen bond donor is ethanol, which has a hydrogen bonded to oxygen; an example of a hydrogen bond acceptor which does not have a hydrogen atom bonded to it is the oxygen atom on diethyl ether. Carbon can also participate in hydrogen bonding, especially when the carbon atom is bound to several electronegative atoms, as is the case in chloroform, CHCl3. The electronegative atom attracts the electron cloud from around the hydrogen nucleus and, by decentralizing the cloud, leaves the atom with a positive partial charge. Because of the small size of hydrogen relative to other atoms and molecules, the resulting charge, though only partial, nevertheless represents a large charge density. A hydrogen bond results when this strong positive charge density attracts a lone pair of electrons on another heteroatom, which becomes the hydrogen-bond acceptor. The hydrogen bond is often described as an electrostatic dipole-dipole interaction. However, it also has some features of covalent bonding: it is directional, strong, produces interatomic distances shorter than sum of van der Waals radii, and usually involves a limited number of interaction partners, which can be interpreted as a kind of valence. These covalent features are more significant when acceptors bind hydrogens from more electronegative donors. The partially covalent nature of a hydrogen bond raises the questions: "To which molecule or atom does the hydrogen nucleus belong?" and "Which should be labeled 'donor' and which 'acceptor'?" Usually, this is easy to determine simply based on interatomic distances in the X-H...Y system: X-H distance is typically ~1.1 Å, whereas H...Y distance is ~ 1.6 to 2.0 Å. Liquids that display hydrogen bonding are called associated liquids. Hydrogen bonds can vary in strength from very weak (1-2 kJ mol−1) to extremely strong (>155 kJ mol−1), as in the ion HF2−. Typical values include: - F—H...:F (155 kJ/mol or 40 kcal/mol) - O—H...:N (29 kJ/mol or 6.9 kcal/mol) - O—H...:O (21 kJ/mol or 5.0 kcal/mol) - N—H...:N (13 kJ/mol or 3.1 kcal/mol) - N—H...:O (8 kJ/mol or 1.9 kcal/mol) - HO—H...:OH3+ (18 kJ/mol or 4.3 kcal/mol) {Data obtained using molecular dynamics as detailed in the reference and should be compared to 7.9 kJ/mol for bulk waters, obtained using the same molecular dynamics.} The length of hydrogen bonds depends on bond strength, temperature, and pressure. The bond strength itself is dependent on temperature, pressure, bond angle, and environment (usually characterized by local dielectric constant). The typical length of a hydrogen bond in water is 1.97 Å (197 pm). # Hydrogen bonds in water The most ubiquitous, and perhaps simplest, example of a hydrogen bond is found between water molecules. In a discrete water molecule, water has two hydrogen atoms and one oxygen atom. Two molecules of water can form a hydrogen bond between them; the simplest case, when only two molecules are present, is called the water dimer and is often used as a model system. When more molecules are present, as is the case in liquid water, more bonds are possible because the oxygen of one water molecule has two lone pairs of electrons, each of which can form a hydrogen bond with hydrogens on two other water molecules. This can repeat so that every water molecule is H-bonded with up to four other molecules, as shown in the figure (two through its two lone pairs, and two through its two hydrogen atoms.) Liquid water's high boiling point is due to the high number of hydrogen bonds each molecule can have relative to its low molecular mass, not to mention the great strength of these hydrogen bonds. Realistically the water molecule has a very high boiling point, melting point and viscosity compared to other similar substances not conjoined by hydrogen bonds. The reasoning for these attributes is the inability to, or the difficulty in, breaking these bonds. Water is unique because its oxygen atom has two lone pairs and two hydrogen atoms, meaning that the total number of bonds of a water molecule is up to four. For example, hydrogen fluoride—which has three lone pairs on the F atom but only one H atom—can have a total of only two bonds (ammonia has the opposite problem: three hydrogen atoms but only one lone pair). The exact number of hydrogen bonds in which a molecule in liquid water participates fluctuates with time and depends on the temperature. From TIP4P liquid water simulations at 25 °C, it was estimated that each water molecule participates in an average of 3.59 hydrogen bonds. At 100 °C, this number decreases to 3.24 due to the increased molecular motion and decreased density, while at 0 °C, the average number of hydrogen bonds increases to 3.69. A more recent study found a much smaller number of hydrogen bonds: 2.357 at 25 °C. The differences may be due to the use of a different method for defining and counting the hydrogen bonds. Where the bond strengths are more equivalent, one might instead find the atoms of two interacting water molecules partitioned into two polyatomic ions of opposite charge, specifically hydroxide (OH−) and hydronium (H3O+). (Hydronium ions are also known as 'hydroxonium' ions.) Indeed, in pure water under conditions of standard temperature and pressure, this latter formulation is applicable only rarely; on average about one in every 5.5 × 108 molecules gives up a proton to another water molecule, in accordance with the value of the dissociation constant for water under such conditions. It is a crucial part of the uniqueness of water. # Bifurcated and over-coordinated hydrogen bonds in water It can be that a single hydrogen atom participates in two hydrogen bonds, rather than one. This type of bonding is called "bifurcated". It was suggested that a bifurcated hydrogen atom is an essential step in water reorientation; however, the case of an oxygen lone pair participating in more than two hydrogens bonds is rarely given attention in the scientific literature. # Hydrogen bonds in DNA and proteins Hydrogen bonding also plays an important role in determining the three-dimensional structures adopted by proteins and nucleic bases. In these macromolecules, bonding between parts of the same macromolecule cause it to fold into a specific shape, which helps determine the molecule's physiological or biochemical role. The double helical structure of DNA, for example, is due largely to hydrogen bonding between the base pairs, which link one complementary strand to the other and enable replication. In proteins, hydrogen bonds form between the backbone oxygens and amide hydrogens. When the spacing of the amino acid residues participating in a hydrogen bond occurs regularly between positions i and i + 4, an alpha helix is formed. When the spacing is less, between positions i and i + 3, then a 310 helix is formed. When two strands are joined by hydrogen bonds involving alternating residues on each participating strand, a beta sheet is formed. Hydrogen bonds also play a part in forming the tertiary structure of protein through interaction of R-groups.(See also protein folding). A special case of intramolecular hydrogen bonds within proteins, poorly shielded from water attack and hence promoting their own dehydration, are called dehydrons. # Symmetric hydrogen bond A symmetric hydrogen bond is a special type of hydrogen bond in which the proton is spaced exactly halfway between two identical atoms. The strength of the bond to each of those atoms is equal. It is an example of a 3-center 4-electron bond. This type of bond is much stronger than "normal" hydrogen bonds, in fact, its strength is comparable to a covalent bond. It is seen in ice at high pressure, and also in the solid phase of many anhydrous acids such as hydrofluoric acid and formic acid at high pressure. It is also seen in the ion −. Much has been done to explain the symmetric hydrogen bond quantum-mechanically, as it seems to violate the duet rule for the first shell: The proton is effectively surrounded by four electrons. Because of this problem, some consider it to be an ionic bond. Symmetric hydrogen bonds have been observed recently spectroscopically in formic acid at high pressure (>GPa). Each hydrogen atom forms a partial covalent bond with two atoms rather than one. Symmetric hydrogen bonds have been postulated in ice at high pressure (ice-X). Low-barrier hydrogen bonds form when the distance between two heteroatoms is very small. # Dihydrogen bond The hydrogen bond can be compared with the closely related dihydrogen bond, which is also an intermolecular bonding interaction involving hydrogen atoms. These structures have been known for some time, and well characterized by crystallography; however, an understanding of their relationship to the conventional hydrogen bond, ionic bond, and covalent bond remains unclear. Generally, the hydrogen bond is characterized by a proton acceptor that is a lone pair of electrons in nonmetallic atoms (most notably in the nitrogen, and chalcogen groups). In some cases, these proton acceptors may be pi-bonds or metal complexes. In the dihydrogen bond, however, a metal hydride serves as a proton acceptor; thus forming a hydrogen-hydrogen interaction. Neutron diffraction has shown that the molecular geometry of these complexes are similar to hydrogen bonds, in that the bond length is very adaptable to the metal complex/hydrogen donor system. # Advanced theory of the hydrogen bond Recently the nature of the bond was elucidated. A widely publicized article proved from interpretations of the anisotropies in the Compton profile of ordinary ice, that the hydrogen bond is partly covalent. Some NMR data on hydrogen bonds in proteins also indicate covalent bonding. Most generally, the hydrogen bond can be viewed as a metric-dependent electrostatic scalar field between two or more intermolecular bonds. This is slightly different from the intramolecular bound states of, for example, covalent or ionic bonds; however, hydrogen bonding is generally still a bound state phenomenon, since the interaction energy has a net negative sum. The initial theory of hydrogen bonding proposed by Linus Pauling suggested that the hydrogen bonds had a partial covalent nature. This remained a controversial conclusion until the late 1990's when NMR techniques were employed by F. Cordier et al. to transfer information between hydrogen-bonded nuclei, a feat that would only be possible if the hydrogen bond contained some covalent character. While a lot of experimental data has been recovered for hydrogen bonds in water, for example, that provide good resolution on the scale of intermolecular distances and molecular thermodynamics, the kinetic and dynamical properties of the hydrogen bond in dynamic systems remains unchanged. # Hydrogen bonding phenomena - Dramatically higher boiling points of NH3, H2O, and HF compared to the heavier analogues PH3, H2S, and HCl - Viscosity of anhydrous phosphoric acid and of glycerol - Dimer formation in carboxylic acids and hexamer formation in hydrogen fluoride, which occur even in the gas phase, resulting in gross deviations from the ideal gas law. - High water solubility of many compounds such as ammonia is explained by hydrogen bonding with water molecules. - Negative azeotropy of mixtures of HF and water - Deliquescence of NaOH is caused in part by reaction of OH- with moisture to form hydrogen-bonded H2O3- species. An analogous process happens between NaNH2 and NH3, and between NaF and HF. - The fact that ice is less dense than liquid water is due to a crystal structure resulting from hydrogen bonds. - The presence of hydrogen bonds can cause an anomaly in the normal succession of states of matter for certain mixtures of chemical compounds as temperature increases or decreases. These compounds can be liquid until a certain temperature, then solid even as the temperature increases, and finally liquid again as the temperature rises over the "anomaly interval"	Hydrogen bond Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] A hydrogen bond is a special type of dipole-dipole force that exists between an electronegative atom and a hydrogen atom bonded to another electronegative atom. This type of force always involves a hydrogen atom and the energy of this attraction is close to that of weak covalent bonds (155 kJ/mol), thus the name - Hydrogen Bonding. These attractions can occur between molecules (intermolecularly), or within different parts of a single molecule (intramolecularly).[2] The hydrogen bond is a very strong fixed dipole-dipole van der Waals-Keesom force, but weaker than covalent, ionic and metallic bonds. The hydrogen bond is somewhere between a covalent bond and an electrostatic intermolecular attraction. Intermolecular hydrogen bonding is responsible for the high boiling point of water (100 °C). This is because of the strong hydrogen bond, as opposed to other group 16 hydrides. Intramolecular hydrogen bonding is partly responsible for the secondary, tertiary, and quaternary structures of proteins and nucleic acids. # Bonding A hydrogen atom attached to a relatively electronegative atom is a hydrogen bond donor. This electronegative atom is usually fluorine, oxygen, or nitrogen. An electronegative atom such as fluorine, oxygen, or nitrogen is a hydrogen bond acceptor, regardless of whether it is bonded to a hydrogen atom or not. An example of a hydrogen bond donor is ethanol, which has a hydrogen bonded to oxygen; an example of a hydrogen bond acceptor which does not have a hydrogen atom bonded to it is the oxygen atom on diethyl ether. Carbon can also participate in hydrogen bonding, especially when the carbon atom is bound to several electronegative atoms, as is the case in chloroform, CHCl3. The electronegative atom attracts the electron cloud from around the hydrogen nucleus and, by decentralizing the cloud, leaves the atom with a positive partial charge. Because of the small size of hydrogen relative to other atoms and molecules, the resulting charge, though only partial, nevertheless represents a large charge density. A hydrogen bond results when this strong positive charge density attracts a lone pair of electrons on another heteroatom, which becomes the hydrogen-bond acceptor. The hydrogen bond is often described as an electrostatic dipole-dipole interaction. However, it also has some features of covalent bonding: it is directional, strong, produces interatomic distances shorter than sum of van der Waals radii, and usually involves a limited number of interaction partners, which can be interpreted as a kind of valence. These covalent features are more significant when acceptors bind hydrogens from more electronegative donors. The partially covalent nature of a hydrogen bond raises the questions: "To which molecule or atom does the hydrogen nucleus belong?" and "Which should be labeled 'donor' and which 'acceptor'?" Usually, this is easy to determine simply based on interatomic distances in the X-H...Y system: X-H distance is typically ~1.1 Å, whereas H...Y distance is ~ 1.6 to 2.0 Å. Liquids that display hydrogen bonding are called associated liquids. Hydrogen bonds can vary in strength from very weak (1-2 kJ mol−1) to extremely strong (>155 kJ mol−1), as in the ion HF2−.[3] Typical values include: - F—H...:F (155 kJ/mol or 40 kcal/mol) - O—H...:N (29 kJ/mol or 6.9 kcal/mol) - O—H...:O (21 kJ/mol or 5.0 kcal/mol) - N—H...:N (13 kJ/mol or 3.1 kcal/mol) - N—H...:O (8 kJ/mol or 1.9 kcal/mol) - HO—H...:OH3+ (18 kJ/mol[4] or 4.3 kcal/mol) {Data obtained using molecular dynamics as detailed in the reference and should be compared to 7.9 kJ/mol for bulk waters, obtained using the same molecular dynamics.} The length of hydrogen bonds depends on bond strength, temperature, and pressure. The bond strength itself is dependent on temperature, pressure, bond angle, and environment (usually characterized by local dielectric constant). The typical length of a hydrogen bond in water is 1.97 Å (197 pm). # Hydrogen bonds in water The most ubiquitous, and perhaps simplest, example of a hydrogen bond is found between water molecules. In a discrete water molecule, water has two hydrogen atoms and one oxygen atom. Two molecules of water can form a hydrogen bond between them; the simplest case, when only two molecules are present, is called the water dimer and is often used as a model system. When more molecules are present, as is the case in liquid water, more bonds are possible because the oxygen of one water molecule has two lone pairs of electrons, each of which can form a hydrogen bond with hydrogens on two other water molecules. This can repeat so that every water molecule is H-bonded with up to four other molecules, as shown in the figure (two through its two lone pairs, and two through its two hydrogen atoms.) Liquid water's high boiling point is due to the high number of hydrogen bonds each molecule can have relative to its low molecular mass, not to mention the great strength of these hydrogen bonds. Realistically the water molecule has a very high boiling point, melting point and viscosity compared to other similar substances not conjoined by hydrogen bonds. The reasoning for these attributes is the inability to, or the difficulty in, breaking these bonds. Water is unique because its oxygen atom has two lone pairs and two hydrogen atoms, meaning that the total number of bonds of a water molecule is up to four. For example, hydrogen fluoride—which has three lone pairs on the F atom but only one H atom—can have a total of only two bonds (ammonia has the opposite problem: three hydrogen atoms but only one lone pair). The exact number of hydrogen bonds in which a molecule in liquid water participates fluctuates with time and depends on the temperature. From TIP4P liquid water simulations at 25 °C, it was estimated that each water molecule participates in an average of 3.59 hydrogen bonds. At 100 °C, this number decreases to 3.24 due to the increased molecular motion and decreased density, while at 0 °C, the average number of hydrogen bonds increases to 3.69.[5] A more recent study found a much smaller number of hydrogen bonds: 2.357 at 25 °C.[6] The differences may be due to the use of a different method for defining and counting the hydrogen bonds. Where the bond strengths are more equivalent, one might instead find the atoms of two interacting water molecules partitioned into two polyatomic ions of opposite charge, specifically hydroxide (OH−) and hydronium (H3O+). (Hydronium ions are also known as 'hydroxonium' ions.) Indeed, in pure water under conditions of standard temperature and pressure, this latter formulation is applicable only rarely; on average about one in every 5.5 × 108 molecules gives up a proton to another water molecule, in accordance with the value of the dissociation constant for water under such conditions. It is a crucial part of the uniqueness of water. # Bifurcated and over-coordinated hydrogen bonds in water It can be that a single hydrogen atom participates in two hydrogen bonds, rather than one. This type of bonding is called "bifurcated". It was suggested that a bifurcated hydrogen atom is an essential step in water reorientation;[7] however, the case of an oxygen lone pair participating in more than two hydrogens bonds is rarely given attention in the scientific literature. # Hydrogen bonds in DNA and proteins Hydrogen bonding also plays an important role in determining the three-dimensional structures adopted by proteins and nucleic bases. In these macromolecules, bonding between parts of the same macromolecule cause it to fold into a specific shape, which helps determine the molecule's physiological or biochemical role. The double helical structure of DNA, for example, is due largely to hydrogen bonding between the base pairs, which link one complementary strand to the other and enable replication. In proteins, hydrogen bonds form between the backbone oxygens and amide hydrogens. When the spacing of the amino acid residues participating in a hydrogen bond occurs regularly between positions i and i + 4, an alpha helix is formed. When the spacing is less, between positions i and i + 3, then a 310 helix is formed. When two strands are joined by hydrogen bonds involving alternating residues on each participating strand, a beta sheet is formed. Hydrogen bonds also play a part in forming the tertiary structure of protein through interaction of R-groups.(See also protein folding). A special case of intramolecular hydrogen bonds within proteins, poorly shielded from water attack and hence promoting their own dehydration, are called dehydrons. # Symmetric hydrogen bond A symmetric hydrogen bond is a special type of hydrogen bond in which the proton is spaced exactly halfway between two identical atoms. The strength of the bond to each of those atoms is equal. It is an example of a 3-center 4-electron bond. This type of bond is much stronger than "normal" hydrogen bonds, in fact, its strength is comparable to a covalent bond. It is seen in ice at high pressure, and also in the solid phase of many anhydrous acids such as hydrofluoric acid and formic acid at high pressure. It is also seen in the ion [F-H-F]−. Much has been done to explain the symmetric hydrogen bond quantum-mechanically, as it seems to violate the duet rule for the first shell: The proton is effectively surrounded by four electrons. Because of this problem, some consider it to be an ionic bond. Symmetric hydrogen bonds have been observed recently spectroscopically in formic acid at high pressure (>GPa). Each hydrogen atom forms a partial covalent bond with two atoms rather than one. Symmetric hydrogen bonds have been postulated in ice at high pressure (ice-X). Low-barrier hydrogen bonds form when the distance between two heteroatoms is very small. # Dihydrogen bond The hydrogen bond can be compared with the closely related dihydrogen bond, which is also an intermolecular bonding interaction involving hydrogen atoms. These structures have been known for some time, and well characterized by crystallography; however, an understanding of their relationship to the conventional hydrogen bond, ionic bond, and covalent bond remains unclear. Generally, the hydrogen bond is characterized by a proton acceptor that is a lone pair of electrons in nonmetallic atoms (most notably in the nitrogen, and chalcogen groups). In some cases, these proton acceptors may be pi-bonds or metal complexes. In the dihydrogen bond, however, a metal hydride serves as a proton acceptor; thus forming a hydrogen-hydrogen interaction. Neutron diffraction has shown that the molecular geometry of these complexes are similar to hydrogen bonds, in that the bond length is very adaptable to the metal complex/hydrogen donor system. # Advanced theory of the hydrogen bond Recently the nature of the bond was elucidated. A widely publicized article[8] proved from interpretations of the anisotropies in the Compton profile of ordinary ice, that the hydrogen bond is partly covalent. Some NMR data on hydrogen bonds in proteins also indicate covalent bonding. Most generally, the hydrogen bond can be viewed as a metric-dependent electrostatic scalar field between two or more intermolecular bonds. This is slightly different from the intramolecular bound states of, for example, covalent or ionic bonds; however, hydrogen bonding is generally still a bound state phenomenon, since the interaction energy has a net negative sum. The initial theory of hydrogen bonding proposed by Linus Pauling suggested that the hydrogen bonds had a partial covalent nature. This remained a controversial conclusion until the late 1990's when NMR techniques were employed by F. Cordier et al. to transfer information between hydrogen-bonded nuclei, a feat that would only be possible if the hydrogen bond contained some covalent character. While a lot of experimental data has been recovered for hydrogen bonds in water, for example, that provide good resolution on the scale of intermolecular distances and molecular thermodynamics, the kinetic and dynamical properties of the hydrogen bond in dynamic systems remains unchanged. # Hydrogen bonding phenomena - Dramatically higher boiling points of NH3, H2O, and HF compared to the heavier analogues PH3, H2S, and HCl - Viscosity of anhydrous phosphoric acid and of glycerol - Dimer formation in carboxylic acids and hexamer formation in hydrogen fluoride, which occur even in the gas phase, resulting in gross deviations from the ideal gas law. - High water solubility of many compounds such as ammonia is explained by hydrogen bonding with water molecules. - Negative azeotropy of mixtures of HF and water - Deliquescence of NaOH is caused in part by reaction of OH- with moisture to form hydrogen-bonded H2O3- species. An analogous process happens between NaNH2 and NH3, and between NaF and HF. - The fact that ice is less dense than liquid water is due to a crystal structure resulting from hydrogen bonds. - The presence of hydrogen bonds can cause an anomaly in the normal succession of states of matter for certain mixtures of chemical compounds as temperature increases or decreases. These compounds can be liquid until a certain temperature, then solid even as the temperature increases, and finally liquid again as the temperature rises over the "anomaly interval"[9] Template:Chemical bonds	https://www.wikidoc.org/index.php/Hydrogen-bonding
b69e135ec725ab19d6875d5e3e9d5a405e5a5e89	wikidoc	Hydrogenation	Hydrogenation # Overview Hydrogenation is a class of chemical reactions which result in an addition of hydrogen (H2) usually to unsaturated organic compounds. Typical substrates include alkenes, alkynes, ketones, nitriles, and imines. Most hydrogenations involve the direct addition of diatomic hydrogen (H2) but some involve the alternative sources of hydrogen, not H2: these processes are called transfer hydrogenations. The reverse reaction, removal of hydrogen, is called dehydrogenation. The classical example of a hydrogenation is the addition of hydrogen on unsaturated bonds between carbon atoms, converting alkenes to alkanes. Numerous important applications are found in the petrochemical, pharmaceutical and food industries. Health concerns associated with the hydrogenation of unsaturated fats to produce saturated fats and trans fats is an important aspect of current consumer awareness. Hydrogenation differs from protonation or hydride addition (e.g. use of sodium borohydride): in hydrogenation, the products have the same charge as the reactants. # The hydrogenation process Hydrogenation has three components: the unsaturated substrate, the hydrogen (or hydrogen source) and, invariably, a catalyst. The largest scale technological uses of H2 are the hydrogenation and hydrogenolysis reactions associated with both heavy and fine chemicals industries. Hydrogenation is the addition of H2 to unsaturated organic compounds such as alkenes to give alkanes and aldehydes to give alcohols. Hydrogenolysis is the cleavage of C-X (X = O, S, N) bonds by H2 to give C-H and H-X bonds. Large-scale applications of hydrogenolysis reactions are associated with the upgrading of fossil fuels. Hydrogenation and hydrogenolysis reactions require metal catalysts, often those composed of platinum or similar precious metals. It is a curious fact that under mild conditions, H2 reacts directly with no organic compound in the absence of such catalysts. The addition of H2 to an alkene affords an alkane in the protypical reaction: ## Catalysts With rare exception, no reaction below 480 °C occurs between H2 and organic compounds in the absence of metal catalysts. The catalyst simultaneously binds both the H2 and the unsaturated substrate and facilitates their union. Platinum group metals, particularly platinum, palladium, rhodium and ruthenium, are highly active catalysts. Highly active catalysts operate at lower temperatures and lower pressures of H2. Non-precious metal catalysts, especially those based on nickel (such as Raney nickel and Urushibara nickel) have also been developed as economical alternatives but they are often slower or require higher temperatures. The trade-off is activity (speed of reaction) vs. cost of the catalyst and cost of the apparatus required for use of high pressures. Two broad families of catalysts are known - homogeneous and heterogeneous. Homogeneous catalysts dissolve in the solvent that contains the unsaturated substrate. Heterogeneous catalysts are solids that are suspended in the same solvent with the substrate or are treated with gaseous substrate. In the pharmaceutical industry and for special chemical applications, soluble ""homogeneous"" catalyst are sometimes employed, such as the rhodium-based compound known as Wilkinson's catalyst, or the iridium-based Crabtree's catalyst. The activity and selectivity of catalysts can be adjusted by changing the environment around the metal, i.e. the coordination sphere. Different faces of a crystalline heterogeneous catalyst display distinct activities, for example. Similarly, heterogeneous catalysts are affected by their supports, i.e. the material upon with the heterogeneous catalyst is bound. Homogeneous catalysts are affected by their ligands. In many cases, highly empirical modifications involve selective "poisons." Thus, a carefully chosen catalyst can be used to hydrogenate some functional groups without affecting others, such as the hydrogenation of alkenes without touching aromatic rings, or the selective hydrogenation of alkynes to alkenes using Lindlar's catalyst. For prochiral substrates, the selectivity of the catalyst can be adjusted such that one enantiomeric product is produced. ## Hydrogenolysis The catalytic hydrogenation of organic sulfur compounds to form gaseous hydrogen sulfide (H2S) is very widely used in petroleum refineries, petrochemical plants and other industries to desulfurize various final products, intermediate products and process feedstocks by converting sulfur compounds to gaseous hydrogen sulfide which is then easily removed by distillation. The gaseous hydrogen sulfide is subsequently recovered in an amine treater and finally converted to elemental sulfur in a Claus process unit. In those industries, desulfurization process units are often referred to as hydrodesulfurizers (HDS) or hydrotreaters (HDT). In the petroleum refining and petrochemical industries, cobalt-molybdenum or nickel-molybdenum catalysts are commonly used for hydrogenation and hydrogenolysis catalysts. ## Mechanism of reaction Because of its technological relevance, metal-catalyzed “activation” of H2, has been the subject of considerable study, focusing on the reaction mechanisms of by which metals mediate these reactions. First of all isotope labeling using deuterium can be used to determine the regiochemistry of the addition: Essentially, the metal binds to both components to give an intermediate alkene-metal(H)2 complex. The general sequence of reactions is: - binding of the hydrogen to give a dihydride complex ("oxidative addition"): - binding of alkene: - transfer of one hydrogen atom from the metal to carbon (migratory insertion) - transfer of the second hydrogen atom from the metal to the alkyl group with simultaneous dissociation of the alkane ("reductive elimination") Preceding the oxidative addition of H2 is the formation of a dihydrogen complex. ## Hydrogen sources The obvious source of H2 is the gas itself, often under pressure. Hydrogen can also be transferred from hydrogen-donor molecules, such as hydrazine, dihydronaphthalene, dihydroanthracene, isopropanol, and formic acid. Transfer hydrogenation can be metal catalysed. Hydrogenation does proceed from some hydrogen donors without catalysts, examples being diimide and aluminium isopropoxide. ## Temperatures The reaction is carried out at different temperatures and pressures depending upon the substrate. Hydrogenation is a strongly exothermic reaction. In the hydrogenation of vegetable oils and fatty acids, for example, the heat released is about 25 kcal per mole (105 kJ/mol), sufficient to raise the temperature of the oil by 1.6-1.7 °C per iodine number drop. # Hydrogenation in the food industry Hydrogenation is widely applied to the processing of vegetable oils and fats. Complete hydrogenation converts unsaturated fatty acids to saturated ones. In practice the process is not usually carried to completion. Since the original oils usually contain more than one double bond per molecule (that is, they are poly-unsaturated), the result is usually described as partially hydrogenated vegetable oil; that is some, but usually not all, of the double bonds in each molecule have been reduced. This is done by adding hydrogen atoms which bond to the carbon, thus occupying a place in the outer orbital of the carbon which would have otherwise been used to bond with the next carbon in the fatty acid chain. Hydrogenation results in the conversion of liquid vegetable oils to solid or semi-solid fats, such as those present in margarine. Changing the degree of saturation of the fat changes some important physical properties such as the melting point, which is why liquid oils become semi-solid. Semi-solid fats are preferred for baking because the way the fat mixes with flour produces a more desirable texture in the baked product. Since partially hydrogenated vegetable oils are cheaper than animal source fats, are available in a wide range of consistencies, and have other desirable characteristics (e.g., increased oxidative stability (longer shelf life)), they are the predominant fats used in most commercial baked goods. Fat blends formulated for this purpose are called shortenings. ## Health implications A side effect of incomplete hydrogenation having implications for human health is the isomerization of the remaining unsaturated carbon bonds. The cis configuration of these double bonds predominates in the unprocessed fats in most edible fat sources, but incomplete hydrogenation partially converts these molecules to trans isomers, which have been implicated in circulatory diseases including heart disease (see trans fats). The catalytic hydrogenation process favors the conversion from cis to trans bonds because the trans configuration has lower energy than the natural cis one. At equilibrium, the trans/cis isomer ratio is about 2:1. Food legislation in the US and codes of practice in EU has long required labels declaring the fat content of foods in retail trade, and more recently, have also required declaration of the trans fat content. In 2006, New York City adopted the US’s first major municipal ban on most artificial trans fats in restaurant cooking. # History The earliest hydrogenation is that of platinum catalyzed addition of hydrogen to oxygen in the Döbereiner's lamp, a device commercialized as early as 1823. The French chemist Paul Sabatier is considered the father of the hydrogenation process. In 1897 he discovered that the introduction of a trace of nickel as a catalyst facilitated the addition of hydrogen to molecules of gaseous carbon compounds in what is now known as the Sabatier process. For this work Sabatier won half of the 1912 Nobel Prize in Chemistry. Wilhelm Normann was awarded a patent in Germany in 1902 and in Britain in 1903 for the hydrogenation of liquid oils using hydrogen gas, which was the beginning of what is now a very large industry world wide. The commercially very important Haber-Bosch process (ammonia hydrogenation) was first described in 1905 and less so Fischer-Tropsch process (carbon monoxide hydrogenation) in 1922. Another commercial application is the oxo process (1938), a hydrogen mediated coupling of aldehydes with alkenes. Wilkinson's catalyst was the first homogeneous catalyst developed in the 1960s and Noyori asymmetric hydrogenation (1987) one of the first applications in asymmetric synthesis. A 2007 review article advocated the use of more hydrogenations in C-C coupling reactions like the oxo process.	Hydrogenation Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview Hydrogenation is a class of chemical reactions which result in an addition of hydrogen (H2) usually to unsaturated organic compounds. Typical substrates include alkenes, alkynes, ketones, nitriles, and imines.[1] Most hydrogenations involve the direct addition of diatomic hydrogen (H2) but some involve the alternative sources of hydrogen, not H2: these processes are called transfer hydrogenations. The reverse reaction, removal of hydrogen, is called dehydrogenation. The classical example of a hydrogenation is the addition of hydrogen on unsaturated bonds between carbon atoms, converting alkenes to alkanes. Numerous important applications are found in the petrochemical, pharmaceutical and food industries. Health concerns associated with the hydrogenation of unsaturated fats to produce saturated fats and trans fats is an important aspect of current consumer awareness. Hydrogenation differs from protonation or hydride addition (e.g. use of sodium borohydride): in hydrogenation, the products have the same charge as the reactants. # The hydrogenation process Hydrogenation has three components: the unsaturated substrate, the hydrogen (or hydrogen source) and, invariably, a catalyst. The largest scale technological uses of H2 are the hydrogenation and hydrogenolysis reactions associated with both heavy and fine chemicals industries. Hydrogenation is the addition of H2 to unsaturated organic compounds such as alkenes to give alkanes and aldehydes to give alcohols. Hydrogenolysis is the cleavage of C-X (X = O, S, N) bonds by H2 to give C-H and H-X bonds. Large-scale applications of hydrogenolysis reactions are associated with the upgrading of fossil fuels. Hydrogenation and hydrogenolysis reactions require metal catalysts, often those composed of platinum or similar precious metals. It is a curious fact that under mild conditions, H2 reacts directly with no organic compound in the absence of such catalysts. The addition of H2 to an alkene affords an alkane in the protypical reaction: ## Catalysts With rare exception, no reaction below 480 °C occurs between H2 and organic compounds in the absence of metal catalysts. The catalyst simultaneously binds both the H2 and the unsaturated substrate and facilitates their union. Platinum group metals, particularly platinum, palladium, rhodium and ruthenium, are highly active catalysts. Highly active catalysts operate at lower temperatures and lower pressures of H2. Non-precious metal catalysts, especially those based on nickel (such as Raney nickel and Urushibara nickel) have also been developed as economical alternatives but they are often slower or require higher temperatures. The trade-off is activity (speed of reaction) vs. cost of the catalyst and cost of the apparatus required for use of high pressures. Two broad families of catalysts are known - homogeneous and heterogeneous. Homogeneous catalysts dissolve in the solvent that contains the unsaturated substrate. Heterogeneous catalysts are solids that are suspended in the same solvent with the substrate or are treated with gaseous substrate. In the pharmaceutical industry and for special chemical applications, soluble ""homogeneous"" catalyst are sometimes employed, such as the rhodium-based compound known as Wilkinson's catalyst, or the iridium-based Crabtree's catalyst. The activity and selectivity of catalysts can be adjusted by changing the environment around the metal, i.e. the coordination sphere. Different faces of a crystalline heterogeneous catalyst display distinct activities, for example. Similarly, heterogeneous catalysts are affected by their supports, i.e. the material upon with the heterogeneous catalyst is bound. Homogeneous catalysts are affected by their ligands. In many cases, highly empirical modifications involve selective "poisons." Thus, a carefully chosen catalyst can be used to hydrogenate some functional groups without affecting others, such as the hydrogenation of alkenes without touching aromatic rings, or the selective hydrogenation of alkynes to alkenes using Lindlar's catalyst. For prochiral substrates, the selectivity of the catalyst can be adjusted such that one enantiomeric product is produced. ## Hydrogenolysis The catalytic hydrogenation of organic sulfur compounds to form gaseous hydrogen sulfide (H2S) is very widely used in petroleum refineries, petrochemical plants and other industries to desulfurize various final products, intermediate products and process feedstocks by converting sulfur compounds to gaseous hydrogen sulfide which is then easily removed by distillation. The gaseous hydrogen sulfide is subsequently recovered in an amine treater and finally converted to elemental sulfur in a Claus process unit. In those industries, desulfurization process units are often referred to as hydrodesulfurizers (HDS) or hydrotreaters (HDT). In the petroleum refining and petrochemical industries, cobalt-molybdenum or nickel-molybdenum catalysts are commonly used for hydrogenation and hydrogenolysis catalysts. ## Mechanism of reaction Because of its technological relevance, metal-catalyzed “activation” of H2, has been the subject of considerable study, focusing on the reaction mechanisms of by which metals mediate these reactions.[2] First of all isotope labeling using deuterium can be used to determine the regiochemistry of the addition: Essentially, the metal binds to both components to give an intermediate alkene-metal(H)2 complex. The general sequence of reactions is: - binding of the hydrogen to give a dihydride complex ("oxidative addition"): - binding of alkene: - transfer of one hydrogen atom from the metal to carbon (migratory insertion) - transfer of the second hydrogen atom from the metal to the alkyl group with simultaneous dissociation of the alkane ("reductive elimination") Preceding the oxidative addition of H2 is the formation of a dihydrogen complex. ## Hydrogen sources The obvious source of H2 is the gas itself, often under pressure. Hydrogen can also be transferred from hydrogen-donor molecules, such as hydrazine,[3][4] dihydronaphthalene, dihydroanthracene, isopropanol, and formic acid.[5][6] Transfer hydrogenation can be metal catalysed. Hydrogenation does proceed from some hydrogen donors without catalysts, examples being diimide and aluminium isopropoxide. ## Temperatures The reaction is carried out at different temperatures and pressures depending upon the substrate. Hydrogenation is a strongly exothermic reaction. In the hydrogenation of vegetable oils and fatty acids, for example, the heat released is about 25 kcal per mole (105 kJ/mol), sufficient to raise the temperature of the oil by 1.6-1.7 °C per iodine number drop. # Hydrogenation in the food industry Template:Fats Hydrogenation is widely applied to the processing of vegetable oils and fats. Complete hydrogenation converts unsaturated fatty acids to saturated ones. In practice the process is not usually carried to completion. Since the original oils usually contain more than one double bond per molecule (that is, they are poly-unsaturated), the result is usually described as partially hydrogenated vegetable oil; that is some, but usually not all, of the double bonds in each molecule have been reduced. This is done by adding hydrogen atoms which bond to the carbon, thus occupying a place in the outer orbital of the carbon which would have otherwise been used to bond with the next carbon in the fatty acid chain. Hydrogenation results in the conversion of liquid vegetable oils to solid or semi-solid fats, such as those present in margarine. Changing the degree of saturation of the fat changes some important physical properties such as the melting point, which is why liquid oils become semi-solid. Semi-solid fats are preferred for baking because the way the fat mixes with flour produces a more desirable texture in the baked product. Since partially hydrogenated vegetable oils are cheaper than animal source fats, are available in a wide range of consistencies, and have other desirable characteristics (e.g., increased oxidative stability (longer shelf life)), they are the predominant fats used in most commercial baked goods. Fat blends formulated for this purpose are called shortenings. ## Health implications A side effect of incomplete hydrogenation having implications for human health is the isomerization of the remaining unsaturated carbon bonds. The cis configuration of these double bonds predominates in the unprocessed fats in most edible fat sources, but incomplete hydrogenation partially converts these molecules to trans isomers, which have been implicated in circulatory diseases including heart disease (see trans fats). The catalytic hydrogenation process favors the conversion from cis to trans bonds because the trans configuration has lower energy than the natural cis one. At equilibrium, the trans/cis isomer ratio is about 2:1. Food legislation in the US and codes of practice in EU has long required labels declaring the fat content of foods in retail trade, and more recently, have also required declaration of the trans fat content. In 2006, New York City adopted the US’s first major municipal ban on most artificial trans fats in restaurant cooking. # History The earliest hydrogenation is that of platinum catalyzed addition of hydrogen to oxygen in the Döbereiner's lamp, a device commercialized as early as 1823. The French chemist Paul Sabatier is considered the father of the hydrogenation process. In 1897 he discovered that the introduction of a trace of nickel as a catalyst facilitated the addition of hydrogen to molecules of gaseous carbon compounds in what is now known as the Sabatier process. For this work Sabatier won half of the 1912 Nobel Prize in Chemistry. Wilhelm Normann was awarded a patent in Germany in 1902 and in Britain in 1903 for the hydrogenation of liquid oils using hydrogen gas, which was the beginning of what is now a very large industry world wide. The commercially very important Haber-Bosch process (ammonia hydrogenation) was first described in 1905 and less so Fischer-Tropsch process (carbon monoxide hydrogenation) in 1922. Another commercial application is the oxo process (1938), a hydrogen mediated coupling of aldehydes with alkenes. Wilkinson's catalyst was the first homogeneous catalyst developed in the 1960s and Noyori asymmetric hydrogenation (1987) one of the first applications in asymmetric synthesis. A 2007 review article advocated the use of more hydrogenations in C-C coupling reactions like the oxo process.[7]	https://www.wikidoc.org/index.php/Hydrogenated
ddab4d277be0084192ef498d42df6ef40eb67e7c	wikidoc	Hymenorrhaphy	Hymenorrhaphy # Overview Hymenorrhaphy or hymen reconstruction surgery is the surgical restoration of the hymen. The term comes from the Greek words hymen meaning membrane, and raphe meaning suture. It is also known as hymenoplasty, although strictly this term would also include hymenotomy. Such procedures are not generally regarded as part of mainstream gynecology, but are available from some plastic surgery centres, particularly in the USA, Japan and Western Europe, generally as day surgery. The normal aim is to cause bleeding during the wedding night, which in some cultures is a required proof of virginity. # Varieties of the operation The term may cover at least four significantly different types of procedure: - Suturing of a tear in the hymen such as might be caused by sexual assault, soon after the assault, to facilitate healing. - A purely cosmetic procedure in which a membrane without blood supply is created, sometimes including a gelatin capsule of an artificial bloodlike substance. This operation is intended to be performed within a few days before an intended marriage. - Use of a flap of the vaginal lining, complete with its blood supply, to create a new hymen. Patients are advised to refrain from penetrative sex for up to three months following these procedures. - The term hymen reconstruction has also been used to describe some varieties of infibulation, requiring further surgery before penetration is possible. # Availability and legality Some hymen reconstruction operations are legal in some countries, while other countries ban all hymenorrhaphy. Infibulation is in general illegal. In the United States of America, hymen restoration is available in private clinics and becoming slightly more common.	Hymenorrhaphy Editors-In-Chief: Martin I. Newman, M.D., FACS, Cleveland Clinic Florida, [1]; Michel C. Samson, M.D., FRCSC, FACS [2] # Overview Hymenorrhaphy or hymen reconstruction surgery is the surgical restoration of the hymen. The term comes from the Greek words hymen meaning membrane, and raphe meaning suture. It is also known as hymenoplasty, although strictly this term would also include hymenotomy. Such procedures are not generally regarded as part of mainstream gynecology, but are available from some plastic surgery centres, particularly in the USA, Japan and Western Europe, generally as day surgery. The normal aim is to cause bleeding during the wedding night, which in some cultures is a required proof of virginity. # Varieties of the operation The term may cover at least four significantly different types of procedure: - Suturing of a tear in the hymen such as might be caused by sexual assault, soon after the assault, to facilitate healing. - A purely cosmetic procedure in which a membrane without blood supply is created, sometimes including a gelatin capsule of an artificial bloodlike substance. This operation is intended to be performed within a few days before an intended marriage. - Use of a flap of the vaginal lining, complete with its blood supply, to create a new hymen. Patients are advised to refrain from penetrative sex for up to three months following these procedures. - The term hymen reconstruction has also been used to describe some varieties of infibulation, requiring further surgery before penetration is possible. # Availability and legality Some hymen reconstruction operations are legal in some countries, while other countries ban all hymenorrhaphy. Infibulation is in general illegal. In the United States of America, hymen restoration is available in private clinics and becoming slightly more common.	https://www.wikidoc.org/index.php/Hymen_reconstruction_surgery
03674b2279932ea4733e26020e2d7224a764eae2	wikidoc	Hyperactivity	Hyperactivity # Overview Hyperactivity can be described as a physical state in which a person is abnormally and easily excitable or exuberant. Strong emotional reactions, impulsive behaivor, and sometimes a short span of attention are also typical for a hyperactive person. Some individuals may show these characteristics naturally, as personality differs from person to person. Nonetheless, when hyperactivity starts to become a problem for the person or others, it may be classified as a medical disorder. The slang term "hyper" is used to describe someone who is in a hyperactive state. # Other causes of hyperactivity There was a great deal of focus on Attention-deficit hyperactivity disorder as a cause of hyperactivity. Other conditions can cause it as well. Normal young children can be very lively and may or may not have short attention spans. Normal teenagers can also appear hyperactive; puberty can cause it. Children who are bored, are suffering from mental conflict, or are having problems at home - which may even include sexual abuse - can be hyperactive. The disorder has a large range of effects on children. Some have learning disabilities, while others may be very gifted, or both. Hyperactivity can also occur because of problems with hearing or vision. Overactive thyroid, lead poisoning, atypical depression, mania, anxiety, sleep deprivation and a range of psychiatric illnesses are some of the potential causes. Severe cases of hyperactivity can be very harmful if left untreated, since hyperactive people seldom think about the consequences of their actions. # Does sugar make one hyperactive? A common belief is that eating too much sugar will make a person hyperactive. This belief is especially prevalent amongst parents and teachers who claim that children's behavior often get more rowdy, excited and energetic after they eat too many sugary food and drinks (such as candy or soda). One particular study found that the perception by parents regarding their children's hyperactivity depended on their belief as to whether they had been given sugar. Other studies have shown that the consumption of sugary items does not cause a measurable increase in hyperactive behavior. Hyperactivity is involved with attention span and personality traits. # Other dietary causes of hyperactivity? A September 2007 article from Southampton University touted by the British Food Standards Agency displayed that a statistically significant increase in the hyperactivity of children occurred after they consumed common artificial food colours and additives from fruit drinks. The list of compounds included the nearly ubiquitous additive in the beverage industry sodium benzoate and the also popular tartrazine, along with quinonline yellow, sunset yellow, carmoisine and allura red. The British Food Standard Agency has revised its stance on these additives; informing parents of children that demonstrate hyperactive behaviour that removal of foods contain the six additives from their diet could have beneficial results on behaviour. Other studies have recommended the Feingold Diet which eliminates several synthetic colors, synthetic flavors, synthetic preservatives, and artificial sweeteners. Scientific studies have shown mixed results in double blind studies of the diet, but recently several reports have been published indicating a statistically significant effect on the behaviour of children on the diet . # Causes ## Common Causes - ADHD - Alcoholism - Amphetamine - Atomoxetine - Bipolar disorder - Brain tumor - Cerebral palsy - Drug Abuse - Hyperthyroidism - Stress - Substance abuse ## Causes by Organ System ## Causes in Alphabetical Order - 49,XXXXY syndrome - Adrenoleukodystrophy - Alcoholism - Allergic irritability syndrome - Allergic tension-fatigue syndrome - Amoxicillin - Amphetamine - Anorexia Nervosa - Arginase deficiency - Armodafinil - Atomoxetine - Attention Deficit Hyperactivity Disorder - Autism - Bipolar - Brain tumor - Bupropion - Cerebral palsy - Chlorpromazine - Chromosome 15 inverted duplication - Chromosome 17, trisomy 17p11.2 - Chromosome 17p, partial deletion - Chromosome 22 Ring - Chromosome 8p deletion syndrome - Chromosome 9, trisomy 9q - Chromosome 9q duplication - Citrullinemia - Clonidine - Dexedrine overdose - Diencephalic syndrome - Dubowitz syndrome - English Ivy poisoning - Ethosuximide - Fetal alcohol syndrome - Fluphenazine - Focal epilepsy syndrome - Fragile-X Syndrome - Graves Disease - Guanfacine - Haloperidol - High T4 syndrome - Lead poisoning - Lissencephaly - Loratadine - Mania - Methylphenidate - Modafinil - Mucopolysaccharidosis - Nabilone - Nicardipine - Occupational lead exposure - Phenol sulfotransferase deficiency - Phenylketonuria - Pitt-Rogers-Danks syndrome - Potocki-Lupski syndrome - Reboxetine - Seckel syndrome - Smith-Magenis syndrome - Strauss syndrome - Stress - Subacute Thyroiditis - Thorazine - Tolcapone - Tuberous sclerosis	Hyperactivity Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief:Aditya Govindavarjhulla, M.B.B.S. [2] # Overview Hyperactivity can be described as a physical state in which a person is abnormally and easily excitable or exuberant. Strong emotional reactions, impulsive behaivor, and sometimes a short span of attention are also typical for a hyperactive person. Some individuals may show these characteristics naturally, as personality differs from person to person. Nonetheless, when hyperactivity starts to become a problem for the person or others, it may be classified as a medical disorder. The slang term "hyper" is used to describe someone who is in a hyperactive state. # Other causes of hyperactivity There was a great deal of focus on Attention-deficit hyperactivity disorder as a cause of hyperactivity. Other conditions can cause it as well. Normal young children can be very lively and may or may not have short attention spans. Normal teenagers can also appear hyperactive; puberty can cause it. Children who are bored, are suffering from mental conflict, or are having problems at home - which may even include sexual abuse - can be hyperactive. The disorder has a large range of effects on children. Some have learning disabilities, while others may be very gifted, or both. Hyperactivity can also occur because of problems with hearing or vision. Overactive thyroid, lead poisoning, atypical depression, mania, anxiety, sleep deprivation and a range of psychiatric illnesses are some of the potential causes. Severe cases of hyperactivity can be very harmful if left untreated, since hyperactive people seldom think about the consequences of their actions. # Does sugar make one hyperactive? A common belief is that eating too much sugar will make a person hyperactive. This belief is especially prevalent amongst parents and teachers who claim that children's behavior often get more rowdy, excited and energetic after they eat too many sugary food and drinks (such as candy or soda). One particular study found that the perception by parents regarding their children's hyperactivity depended on their belief as to whether they had been given sugar. Other studies have shown that the consumption of sugary items does not cause a measurable increase in hyperactive behavior.[1] Hyperactivity is involved with attention span and personality traits.[3] # Other dietary causes of hyperactivity? A September 2007 article from Southampton University touted by the British Food Standards Agency displayed that a statistically significant increase in the hyperactivity of children occurred after they consumed common artificial food colours and additives from fruit drinks. The list of compounds included the nearly ubiquitous additive in the beverage industry sodium benzoate and the also popular tartrazine, along with quinonline yellow, sunset yellow, carmoisine and allura red. The British Food Standard Agency has revised its stance on these additives; informing parents of children that demonstrate hyperactive behaviour that removal of foods contain the six additives from their diet could have beneficial results on behaviour.[4] Other studies have recommended the Feingold Diet which eliminates several synthetic colors, synthetic flavors, synthetic preservatives, and artificial sweeteners. Scientific studies have shown mixed results in double blind studies of the diet[1], but recently several reports have been published indicating a statistically significant effect on the behaviour of children on the diet [2][3]. # Causes ## Common Causes - ADHD - Alcoholism - Amphetamine - Atomoxetine - Bipolar disorder - Brain tumor - Cerebral palsy - Drug Abuse - Hyperthyroidism - Stress - Substance abuse ## Causes by Organ System ## Causes in Alphabetical Order - 49,XXXXY syndrome - Adrenoleukodystrophy - Alcoholism - Allergic irritability syndrome - Allergic tension-fatigue syndrome - Amoxicillin - Amphetamine - Anorexia Nervosa - Arginase deficiency - Armodafinil - Atomoxetine - Attention Deficit Hyperactivity Disorder - Autism - Bipolar - Brain tumor - Bupropion - Cerebral palsy - Chlorpromazine - Chromosome 15 inverted duplication - Chromosome 17, trisomy 17p11.2 - Chromosome 17p, partial deletion - Chromosome 22 Ring - Chromosome 8p deletion syndrome - Chromosome 9, trisomy 9q - Chromosome 9q duplication - Citrullinemia - Clonidine - Dexedrine overdose - Diencephalic syndrome - Dubowitz syndrome - English Ivy poisoning - Ethosuximide - Fetal alcohol syndrome - Fluphenazine - Focal epilepsy syndrome - Fragile-X Syndrome - Graves Disease - Guanfacine - Haloperidol - High T4 syndrome - Lead poisoning - Lissencephaly - Loratadine - Mania - Methylphenidate - Modafinil - Mucopolysaccharidosis - Nabilone - Nicardipine - Occupational lead exposure - Phenol sulfotransferase deficiency - Phenylketonuria - Pitt-Rogers-Danks syndrome - Potocki-Lupski syndrome - Reboxetine - Seckel syndrome - Smith-Magenis syndrome - Strauss syndrome - Stress - Subacute Thyroiditis - Thorazine - Tolcapone - Tuberous sclerosis	https://www.wikidoc.org/index.php/Hyperactive
abcc1d82b17fe421d6f467f9c3eee2692f27bda7	wikidoc	Hyperesthesia	Hyperesthesia # Overview Hyperesthesia (or Hyperaesthesia) is a condition that involves an abnormal increase in sensitivity to stimuli of the senses. Stimuli of the senses can include sound that one hears, foods that one tastes, textures that one feels, and so forth. Increased touch sensitivity is referred to as "tactile hyperesthesia", and increased sound sensitivity is called "auditory hyperesthesia". # Causes Excessive consumption of caffeine can temporarily induce this condition in humans, due to excessive stimulaton of the spinal cord, as well as the cortex and medulla in the central nervous system. However, this is far from the only cause, and usually wears off after 3-5 hours. ## Drug Causes - Ixabepilone	Hyperesthesia Template:Search infobox Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview Hyperesthesia (or Hyperaesthesia) is a condition that involves an abnormal increase in sensitivity to stimuli of the senses. Stimuli of the senses can include sound that one hears, foods that one tastes, textures that one feels, and so forth. Increased touch sensitivity is referred to as "tactile hyperesthesia", and increased sound sensitivity is called "auditory hyperesthesia". # Causes Excessive consumption of caffeine can temporarily induce this condition in humans,[1] due to excessive stimulaton of the spinal cord, as well as the cortex and medulla in the central nervous system. However, this is far from the only cause, and usually wears off after 3-5 hours. ## Drug Causes - Ixabepilone	https://www.wikidoc.org/index.php/Hyperaesthesia
d14457c8b161c7e823813713088ee6a11afb44c1	wikidoc	Hypermobility	Hypermobility # Overview Hypermobility (also called double-jointedness, hypermobility syndrome or hyperlaxity) describes joints that stretch farther than is normal. For example, some hypermobile people can bend their thumbs backwards to their wrists, or bend their knee joints backwards. It can affect a single joint or multiple joints throughout the body. # Causes Hypermobility generally results from one or more of the following: - Misaligned joints - Abnormally-shaped ends of one or more bones at a joint - A Type 1 collagen defect (found in Ehlers-Danlos Syndrome, Marfan syndrome) results in weakened ligaments, muscles & tendons. This same defective process also results in weakened bones which may result in osteoporosis and fractures - Abnormal joint proprioception (an impaired ability to determine where in space parts of the body are, and how stretched a joint is) The condition tends to run in families, suggesting that there may be a genetic basis for at least some forms of hypermobility. The term double jointed is often used to describe hypermobility, however the name is a misnomer and is not to be taken literally, as an individual with hypermobility in a joint does not actually have two separate joints where others would have just the one. Some people have hypermobility with no other symptoms or medical conditions. However, people with hypermobility syndrome may experience many difficulties. For example, their joints may be easily injured, and they may develop problems from muscle overuse (as muscles must work harder to compensate for the excessive weakness in the ligaments that support the joints). Hypermobility may also be symptomatic of a serious medical condition, such as Ehlers-Danlos Syndrome, Marfan syndrome, rheumatoid arthritis, osteogenesis imperfecta, lupus, polio, down syndrome, morquio syndrome, cleidocranial dysostosis or myotonia congenita. In addition, hypermobility has been associated with chronic fatigue syndrome and fibromyalgia. # Hypermobility Syndrome Hypermobility syndrome (known by a variety of other names, including Benign Joint Hypermobility Syndrome) is generally considered to comprise hypermobility together with other symptoms, such as myalgia and arthralgia, and extra-articular features such as skin hyperextensibility and varicose veins. It affects more females than males. The current diagnostic criteria for hypermobility syndrome are the Brighton criteria, which incorporates the Beighton score. Hypermobility syndrome is considered by many doctors expert in hypermobility (e.g. Professor Rodney Grahame) to be equivalent to the Hypermobile Type of Ehlers-Danlos Syndrome. People with hypermobility syndrome may develop other conditions caused by their lax connective tissues. These conditions include - Gastroesophageal Reflux Disease (GERD) - Irritable Bowel Syndrome (IBS) - Varicose Veins - Flat feet, pronated feet, plantar fasciitis or sesamoiditis and unsupportive shoes - Idiopathic scoliosis - Joint instability causing frequent sprains, tendinitis, or bursitis when doing activities that would not affect the normal individual. - Early-onset osteoarthritis - There is evidence linking hypermobility syndrome to anxiety and depression. - Subluxations or dislocations, especially in the shoulder. - Knee pain - Back pain, prolapsed discs or spondylolisthesis - Hernias - Bruising easily - Worsening of symptoms in cold weather - Joints that make clicking noises - Headaches - Susceptibility to whiplash - Temporomandibular Joint Syndrome also known as TMJ syndrome - Increased nerve compression disorders (i.e. carpal tunnel syndrome) - Mitral valve prolapse - Uterine prolapse # Treatments ## Physical therapy It is important that the individual with hypermobility remain extremely fit - even more so than the average individual - to prevent recurrent injuries. Regular exercise and physical therapy or hydrotherapy can reduce symptoms of hypermobility, because strong muscles help to stabilize joints. These treatments can also help by stretching tight, overused muscles and ensuring that the person can use their full, hypermobile range of motion. Low-impact exercise such as Pilates is usually recommended for hypermobile people as it is less likely to cause injury than high-impact exercise or contact sports. Moist hot packs can relieve the pain of aching joints and muscles. For some patients, ice packs also help to relieve pain. ## Medication Medications frequently used to reduce pain and inflammation caused by hypermobility include analgesics, anti-inflammatory drugs, and tricyclic antidepressants. Some people with hypermobility may benefit from other medications such as steroid injections or gabapentin, a drug originally used for treating epilepsy. ## Lifestyle modification For many people with hypermobility, lifestyle changes decrease the severity of symptoms. For example: - If writing is painful, people may be able to reduce the pain by typing. - If typing is painful, they may try voice control software for their computer. - They should avoid over-stretching the joints - stretching to one's maximum capabilities may result in injuries. Just because they are able to stretch much further, doesn't mean that it is a good idea. - They should watch their posture to make sure they are standing or sitting up straight. Weakened ligaments & muscles contribute to poor posture which may result in numerous other medical conditions. ## Other treatments - Bracing to support weak joints may be helpful, but caution must be used not to weaken the joints further. - Those who are overweight should lose weight. The extra weight puts additional stress on the already weakened ligaments, making them more susceptible to injury.	Hypermobility Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2] # Overview Hypermobility (also called double-jointedness, hypermobility syndrome or hyperlaxity) describes joints that stretch farther than is normal. For example, some hypermobile people can bend their thumbs backwards to their wrists, or bend their knee joints backwards. It can affect a single joint or multiple joints throughout the body. # Causes Hypermobility generally results from one or more of the following: - Misaligned joints - Abnormally-shaped ends of one or more bones at a joint - A Type 1 collagen defect (found in Ehlers-Danlos Syndrome, Marfan syndrome) results in weakened ligaments, muscles & tendons. This same defective process also results in weakened bones which may result in osteoporosis and fractures - Abnormal joint proprioception (an impaired ability to determine where in space parts of the body are, and how stretched a joint is) The condition tends to run in families, suggesting that there may be a genetic basis for at least some forms of hypermobility. The term double jointed is often used to describe hypermobility, however the name is a misnomer and is not to be taken literally, as an individual with hypermobility in a joint does not actually have two separate joints where others would have just the one. Some people have hypermobility with no other symptoms or medical conditions. However, people with hypermobility syndrome may experience many difficulties. For example, their joints may be easily injured, and they may develop problems from muscle overuse (as muscles must work harder to compensate for the excessive weakness in the ligaments that support the joints). Hypermobility may also be symptomatic of a serious medical condition, such as Ehlers-Danlos Syndrome, Marfan syndrome, rheumatoid arthritis, osteogenesis imperfecta, lupus, polio, down syndrome, morquio syndrome, cleidocranial dysostosis or myotonia congenita. In addition, hypermobility has been associated with chronic fatigue syndrome and fibromyalgia. # Hypermobility Syndrome Hypermobility syndrome (known by a variety of other names, including Benign Joint Hypermobility Syndrome) is generally considered to comprise hypermobility together with other symptoms, such as myalgia and arthralgia, and extra-articular features such as skin hyperextensibility and varicose veins. It affects more females than males. The current diagnostic criteria for hypermobility syndrome are the Brighton criteria, which incorporates the Beighton score[3]. Hypermobility syndrome is considered by many doctors expert in hypermobility (e.g. Professor Rodney Grahame) to be equivalent to the Hypermobile Type of Ehlers-Danlos Syndrome. People with hypermobility syndrome may develop other conditions caused by their lax connective tissues. These conditions include - Gastroesophageal Reflux Disease (GERD) - Irritable Bowel Syndrome (IBS) - Varicose Veins - Flat feet, pronated feet, plantar fasciitis or sesamoiditis and unsupportive shoes - Idiopathic scoliosis - Joint instability causing frequent sprains, tendinitis, or bursitis when doing activities that would not affect the normal individual. - Early-onset osteoarthritis - There is evidence linking hypermobility syndrome to anxiety and depression. [4][5] - Subluxations or dislocations, especially in the shoulder. - Knee pain - Back pain, prolapsed discs or spondylolisthesis - Hernias - Bruising easily - Worsening of symptoms in cold weather - Joints that make clicking noises - Headaches - Susceptibility to whiplash - Temporomandibular Joint Syndrome also known as TMJ syndrome - Increased nerve compression disorders (i.e. carpal tunnel syndrome) - Mitral valve prolapse - Uterine prolapse # Treatments ## Physical therapy It is important that the individual with hypermobility remain extremely fit - even more so than the average individual - to prevent recurrent injuries. Regular exercise and physical therapy or hydrotherapy can reduce symptoms of hypermobility, because strong muscles help to stabilize joints. These treatments can also help by stretching tight, overused muscles and ensuring that the person can use their full, hypermobile range of motion. Low-impact exercise such as Pilates is usually recommended for hypermobile people as it is less likely to cause injury than high-impact exercise or contact sports. Moist hot packs can relieve the pain of aching joints and muscles. For some patients, ice packs also help to relieve pain. ## Medication Medications frequently used to reduce pain and inflammation caused by hypermobility include analgesics, anti-inflammatory drugs, and tricyclic antidepressants. Some people with hypermobility may benefit from other medications such as steroid injections or gabapentin, a drug originally used for treating epilepsy. ## Lifestyle modification For many people with hypermobility, lifestyle changes decrease the severity of symptoms. For example: - If writing is painful, people may be able to reduce the pain by typing. - If typing is painful, they may try voice control software for their computer. - They should avoid over-stretching the joints - stretching to one's maximum capabilities may result in injuries. Just because they are able to stretch much further, doesn't mean that it is a good idea. - They should watch their posture to make sure they are standing or sitting up straight. Weakened ligaments & muscles contribute to poor posture which may result in numerous other medical conditions. ## Other treatments - Bracing to support weak joints may be helpful, but caution must be used not to weaken the joints further. - Those who are overweight should lose weight. The extra weight puts additional stress on the already weakened ligaments, making them more susceptible to injury.	https://www.wikidoc.org/index.php/Hypermobile
352c64d3ff53356299a4806a49f74bcc5959ae8b	wikidoc	Hypermotility	Hypermotility Motility is a biological term which refers to the ability to move spontaneously and independently. It can apply to either single-celled or multicellular organisms. In cellular biology or biomedical engineering, motility often refers to directed cell movement down gradients established in biopolymers. Examples are: - movement along a chemical gradient (see chemotaxis) - movement along a rigidity gradient (see durotaxis) - movement along a gradient of cell adhesion sites (see haptotaxis) de:Motilität ms:Motiliti simple:Motile	Hypermotility Motility is a biological term which refers to the ability to move spontaneously and independently. It can apply to either single-celled or multicellular organisms. In cellular biology or biomedical engineering, motility often refers to directed cell movement down gradients established in biopolymers. Examples are: - movement along a chemical gradient (see chemotaxis) - movement along a rigidity gradient (see durotaxis) - movement along a gradient of cell adhesion sites (see haptotaxis) de:Motilität ms:Motiliti simple:Motile Template:WH Template:WS	https://www.wikidoc.org/index.php/Hypermotility
c4ae079484de34d7b125e79cbc52ce8bf1ef6eaa	wikidoc	Hyperoxaluria	Hyperoxaluria # Overview Hyperoxaluria is an excessive urinary excretion of oxalate. Individuals with hyperoxaluria often have calcium oxalate kidney stones. It is sometimes called Bird's disease, after Golding Bird, who first described the condition. # Historical Perspective # Classification ## Types - Primary hyperoxaluria - Enteric hyperoxaluria - Idiopathic hyperoxaluria - Oxalate poisoning # Pathophysiology ## Controversy Perhaps the key difficulty in understanding pathogenesis of primary hyperoxaluria, or more specifically, why AGXT ends up in mitochondria instead of peroxisomes, stems from AGXT's somewhat peculiar evolution. Namely, prior to its current peroxysomal 'destiny', AGXT indeed used to be bound to mitochondria. AGXT's peroxisomal targeting sequence is uniquely specific for mammalian species, suggesting the presence of additional peroxisomal targeting information elsewhere in the AGT molecule. As AGXT was redirected to peroxisomes over the course of evolution, it is plausible that its current aberrant localization to mitochondria owes to some hidden molecular signature in AGXT's spatial configuration unmasked by PH1 mutations affecting the AGXT gene. # Causes Type I (PH1) is associated with AGXT protein, a key enzyme involved in breakdown of oxalate. PH1 is also an example of a protein mistargeting disease, wherein AGXT shows a trafficking defect: instead of being trafficked to peroxisomes, it is targeted to mitochondria, where it is metabolically deficient despite being catalytically active. Type II is associated with GRHPR. It is also a complication of jejunoileal bypass, or in any patient who has lost much of the ileum with an intact colon. This is due to excessive absorption of oxalate from the colon. # Differentiating Hyperoxaluria from Other Diseases # Epidemiology and Demographics # Risk Factors # Screening # Natural History, Complications, and Prognosis # Diagnosis ## Diagnostic Criteria ## History and Symptoms ## Physical Examination ## Laboratory Findings ## Imaging Findings ## Other Diagnostic Studies # Treatment The main therapeutic approach to primary hyperoxaluria is still restricted to symptomatic treatment, i.e. kidney transplantation once the disease has already reached mature or terminal stages. However, through genomics and proteomics approaches, efforts are currently being made to elucidate the kinetics of AGXT folding which has a direct bearing on its targeting to appropriate subcellular localization. Secondary hyperoxaluria is much more common than primary hyperoxaluria, and should be treated by limiting dietary oxalate and providing calcium supplementation. A child with primary hyperoxaluria was treated with a liver and kidney transplant. A favorable outcome is more likely if a kidney transplant is complemented by a liver transplant, given the disease originates in the liver. ## Medical Therapy ## Surgery ## Prevention	Hyperoxaluria Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: # Overview Hyperoxaluria is an excessive urinary excretion of oxalate. Individuals with hyperoxaluria often have calcium oxalate kidney stones. It is sometimes called Bird's disease, after Golding Bird, who first described the condition. # Historical Perspective # Classification ## Types - Primary hyperoxaluria - Enteric hyperoxaluria - Idiopathic hyperoxaluria - Oxalate poisoning # Pathophysiology ## Controversy Perhaps the key difficulty in understanding pathogenesis of primary hyperoxaluria, or more specifically, why AGXT ends up in mitochondria instead of peroxisomes, stems from AGXT's somewhat peculiar evolution. Namely, prior to its current peroxysomal 'destiny', AGXT indeed used to be bound to mitochondria. AGXT's peroxisomal targeting sequence is uniquely specific for mammalian species, suggesting the presence of additional peroxisomal targeting information elsewhere in the AGT molecule. As AGXT was redirected to peroxisomes over the course of evolution, it is plausible that its current aberrant localization to mitochondria owes to some hidden molecular signature in AGXT's spatial configuration unmasked by PH1 mutations affecting the AGXT gene. # Causes Type I (PH1) is associated with AGXT protein, a key enzyme involved in breakdown of oxalate. PH1 is also an example of a protein mistargeting disease, wherein AGXT shows a trafficking defect: instead of being trafficked to peroxisomes, it is targeted to mitochondria, where it is metabolically deficient despite being catalytically active. Type II is associated with GRHPR.[1] It is also a complication of jejunoileal bypass, or in any patient who has lost much of the ileum with an intact colon. This is due to excessive absorption of oxalate from the colon.[2] # Differentiating Hyperoxaluria from Other Diseases # Epidemiology and Demographics # Risk Factors # Screening # Natural History, Complications, and Prognosis # Diagnosis ## Diagnostic Criteria ## History and Symptoms ## Physical Examination ## Laboratory Findings ## Imaging Findings ## Other Diagnostic Studies # Treatment The main therapeutic approach to primary hyperoxaluria is still restricted to symptomatic treatment, i.e. kidney transplantation once the disease has already reached mature or terminal stages. However, through genomics and proteomics approaches, efforts are currently being made to elucidate the kinetics of AGXT folding which has a direct bearing on its targeting to appropriate subcellular localization. Secondary hyperoxaluria is much more common than primary hyperoxaluria, and should be treated by limiting dietary oxalate and providing calcium supplementation. A child with primary hyperoxaluria was treated with a liver and kidney transplant.[3] A favorable outcome is more likely if a kidney transplant is complemented by a liver transplant, given the disease originates in the liver. ## Medical Therapy ## Surgery ## Prevention # External links - GeneReviews/NIH/NCBI/UW entry on Primary Hyperoxaluria Type 1	https://www.wikidoc.org/index.php/Hyperoxaluria
cfe8be620ca80af1101b302d1f9c086948d4dfca	wikidoc	Hyperprosexia	Hyperprosexia Aprosexia, Hyperprosexia, and Paraprosexia are closely related medical and neuro-psychiatric phenomena associated with attention and concentration. They typically occurs in patients suffering traumatic brain injuries. Aprosexia is an abnormal inability to pay attention, characterized by a near-complete indifference to everything. Hyperprosexia is the abnormal state in which a person concentrates on one thing to the exclusion of everything else. Paraprosexia is the inability to pay attention to any one thing (a state of constant distraction). # Etiology Patients suffering traumatic brain injury experience profound disturbance of the basic functions of the cognitive, behavioral, emotional and intellectual systems. Such patients' ability to regulate interaction between the ego and the external world is greatly diminished and they typically exhibit inflexible, concrete and sometimes inappropriate behaviors.	Hyperprosexia Aprosexia, Hyperprosexia, and Paraprosexia are closely related medical and neuro-psychiatric phenomena associated with attention and concentration. They typically occurs in patients suffering traumatic brain injuries. Aprosexia is an abnormal inability to pay attention, characterized by a near-complete indifference to everything. Hyperprosexia is the abnormal state in which a person concentrates on one thing to the exclusion of everything else. Paraprosexia is the inability to pay attention to any one thing (a state of constant distraction). # Etiology Patients suffering traumatic brain injury experience profound disturbance of the basic functions of the cognitive, behavioral, emotional and intellectual systems. Such patients' ability to regulate interaction between the ego and the external world is greatly diminished and they typically exhibit inflexible, concrete and sometimes inappropriate behaviors.	https://www.wikidoc.org/index.php/Hyperprosexia
981e1dba23c6ed58f3135f5efaa2983344efc212	wikidoc	Hypomenorrhea	Hypomenorrhea Hypomenorrhea also known as or related to hypomenorrhoea, scanty periods, and spotting at periods is menstrual blood flow that is extremely light. It is the opposite of Hypermenorrhea which is more properly called Menorrhagia. One cause of hypomenorrhea is Asherman's syndrome (intrauterine adhesions), of which hypomenorrhea (or amenorrhea) may be the only apparent sign. The degree of menstrual deficiency is closely correlated to the extent of the adhesions. # Notes - ↑ Toaff R, Ballas S (1978). "Traumatic hypomenorrhea-amenorrhea (Asherman's syndrome)". Fertil. Steril. 30 (4): 379–87. PMID 568569..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}	Hypomenorrhea Hypomenorrhea also known as or related to hypomenorrhoea, scanty periods, and spotting at periods is menstrual blood flow that is extremely light. It is the opposite of Hypermenorrhea which is more properly called Menorrhagia. One cause of hypomenorrhea is Asherman's syndrome (intrauterine adhesions), of which hypomenorrhea (or amenorrhea) may be the only apparent sign. The degree of menstrual deficiency is closely correlated to the extent of the adhesions.[1] # Notes - ↑ Toaff R, Ballas S (1978). "Traumatic hypomenorrhea-amenorrhea (Asherman's syndrome)". Fertil. Steril. 30 (4): 379–87. PMID 568569..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}	https://www.wikidoc.org/index.php/Hypomenorrhea
faf129a086f5b52dabdafff9a86329cb263ef68d	wikidoc	Hyponephrosis	Hyponephrosis # Overview # Historical Perspective - was first discovered by , a , in during/following . - In , mutations were first identified in the pathogenesis of . - In , the first was developed by to treat/diagnose . # Classification - may be classified according to into subtypes/groups: - Other variants of include , , and . # Pathophysiology - The pathogenesis of is characterized by , , and . - The gene/Mutation in has been associated with the development of , involving the pathway. - On gross pathology, , , and are characteristic findings of . - On microscopic histopathological analysis, , , and are characteristic findings of . # Clinical Features # Differentiating from other Diseases - must be differentiated from other diseases that cause , , and , such as: # Epidemiology and Demographics - The prevalence of is approximately per 100,000 individuals worldwide. - In , the incidence of was estimated to be cases per 100,000 individuals in . ## Age - Patients of all age groups may develop . - is more commonly observed among patients aged years old. - is more commonly observed among . ## Gender - affects men and women equally. - are more commonly affected with than . - The to ratio is approximately to 1. ## Race - There is no racial predilection for . - usually affects individuals of the race. - individuals are less likely to develop . # Risk Factors - Common risk factors in the development of are , , , and . # Natural History, Complications and Prognosis - The majority of patients with remain asymptomatic for . - Early clinical features include , , and . - If left untreated, of patients with may progress to develop , , and . - Common complications of include , , and . - Prognosis is generally , and the of patients with is approximately . # Diagnosis ## Diagnostic Criteria - The diagnosis of is made when at least of the following diagnostic criteria are met: ## Symptoms - is usually asymptomatic. - Symptoms of may include the following: ## Physical Examination - Patients with usually appear . - Physical examination may be remarkable for: ## Laboratory Findings - There are no specific laboratory findings associated with . - A is diagnostic of . - An concentration of is diagnostic of . - Other laboratory findings consistent with the diagnosis of include , , and . ## Imaging Findings - There are no findings associated with . - is the imaging modality of choice for . - On , is characterized by , , and . - may demonstrate , , and . ## Other Diagnostic Studies - may also be diagnosed using . - Findings on include , , and . # Treatment ## Medical Therapy - There is no treatment for ; the mainstay of therapy is supportive care. - The mainstay of therapy for is and . - acts by . - Response to can be monitored with every . ## Surgery - Surgery is the mainstay of therapy for . - in conjunction with is the most common approach to the treatment of . - can only be performed for patients with . ## Prevention - There are no primary preventive measures available for . - Effective measures for the primary prevention of include , , and . - Once diagnosed and successfully treated, patients with are followed-up every . Follow-up testing includes , , and .	Hyponephrosis Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview # Historical Perspective - [Disease name] was first discovered by [scientist name], a [nationality + occupation], in [year] during/following [event]. - In [year], [gene] mutations were first identified in the pathogenesis of [disease name]. - In [year], the first [discovery] was developed by [scientist] to treat/diagnose [disease name]. # Classification - [Disease name] may be classified according to [classification method] into [number] subtypes/groups: - [group1] - [group2] - [group3] - Other variants of [disease name] include [disease subtype 1], [disease subtype 2], and [disease subtype 3]. # Pathophysiology - The pathogenesis of [disease name] is characterized by [feature1], [feature2], and [feature3]. - The [gene name] gene/Mutation in [gene name] has been associated with the development of [disease name], involving the [molecular pathway] pathway. - On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name]. - On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name]. # Clinical Features # Differentiating [disease name] from other Diseases - [Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as: - [Differential dx1] - [Differential dx2] - [Differential dx3] # Epidemiology and Demographics - The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide. - In [year], the incidence of [disease name] was estimated to be [number or range] cases per 100,000 individuals in [location]. ## Age - Patients of all age groups may develop [disease name]. - [Disease name] is more commonly observed among patients aged [age range] years old. - [Disease name] is more commonly observed among [elderly patients/young patients/children]. ## Gender - [Disease name] affects men and women equally. - [Gender 1] are more commonly affected with [disease name] than [gender 2]. - The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1. ## Race - There is no racial predilection for [disease name]. - [Disease name] usually affects individuals of the [race 1] race. - [Race 2] individuals are less likely to develop [disease name]. # Risk Factors - Common risk factors in the development of [disease name] are [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4]. # Natural History, Complications and Prognosis - The majority of patients with [disease name] remain asymptomatic for [duration/years]. - Early clinical features include [manifestation 1], [manifestation 2], and [manifestation 3]. - If left untreated, [#%] of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3]. - Common complications of [disease name] include [complication 1], [complication 2], and [complication 3]. - Prognosis is generally [excellent/good/poor], and the [1/5/10year mortality/survival rate] of patients with [disease name] is approximately [#%]. # Diagnosis ## Diagnostic Criteria - The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met: - [criterion 1] - [criterion 2] - [criterion 3] - [criterion 4] ## Symptoms - [Disease name] is usually asymptomatic. - Symptoms of [disease name] may include the following: - [symptom 1] - [symptom 2] - [symptom 3] - [symptom 4] - [symptom 5] - [symptom 6] ## Physical Examination - Patients with [disease name] usually appear [general appearance]. - Physical examination may be remarkable for: - [finding 1] - [finding 2] - [finding 3] - [finding 4] - [finding 5] - [finding 6] ## Laboratory Findings - There are no specific laboratory findings associated with [disease name]. - A [positive/negative] [test name] is diagnostic of [disease name]. - An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name]. - Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3]. ## Imaging Findings - There are no [imaging study] findings associated with [disease name]. - [Imaging study 1] is the imaging modality of choice for [disease name]. - On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3]. - [Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3]. ## Other Diagnostic Studies - [Disease name] may also be diagnosed using [diagnostic study name]. - Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3]. # Treatment ## Medical Therapy - There is no treatment for [disease name]; the mainstay of therapy is supportive care. - The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2]. - [Medical therapy 1] acts by [mechanism of action 1]. - Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration]. ## Surgery - Surgery is the mainstay of therapy for [disease name]. - [Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name]. - [Surgical procedure] can only be performed for patients with [disease stage] [disease name]. ## Prevention - There are no primary preventive measures available for [disease name]. - Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3]. - Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].	https://www.wikidoc.org/index.php/Hyponephrosis
5e4abd8f640fbe23a0b9a23e80bc15e2fa02c0e5	wikidoc	Hypoxic drive	Hypoxic drive The hypoxic drive is a form of respiratory drive in which the body uses oxygen chemoreceptors instead of carbon dioxide receptors to regulate the respiratory cycle. Normal respiration is driven mostly by the levels of carbon dioxide in the arteries, which are detected by peripheral chemoreceptors, and very little by the oxygen levels. An increase in carbon dioxide will cause chemoreceptor reflexes to trigger an increase in respirations. However in cases where there are chronically high carbon dioxide levels in the blood such as in COPD patients, the body will begin to rely more on the oxygen receptors and less on the carbon dioxide receptors. In this case, when there is an increase in oxygen levels, the body will decrease the respirations. If a person with chronic hypoxic drive enters acute respiratory distress, healthcare providers who are unaware of their condition may provide oxygen therapy as an initial treatment. The reaction to increased oxygen causes the oxygen receptors to decrease respirations, possibly to the point of respiratory arrest. For this reason, people with hypoxic drive must not receive oxygen in high concentrations or for long periods. Treatment of a patient in acute respiratory distress with hypoxic drive can still be given oxygen therapy, however to avoid having the situation deteriorate to full respiratory arrest, arterial blood gas levels should be closely monitored via pulse oximetry and respirations should also be closely monitored. # See Also - Respiratory System - Homeostasis Normal respiration is driven mostly by the levels of carbon dioxide in the blood, which are detected by central chemoreceptors, via a change in pH. It has very little by the oxygen levels. An increase in carbon dioxide will cause chemoreceptor reflexes to trigger an increase in respirations.	Hypoxic drive The hypoxic drive is a form of respiratory drive in which the body uses oxygen chemoreceptors instead of carbon dioxide receptors to regulate the respiratory cycle. Normal respiration is driven mostly by the levels of carbon dioxide in the arteries, which are detected by peripheral chemoreceptors, and very little by the oxygen levels. An increase in carbon dioxide will cause chemoreceptor reflexes to trigger an increase in respirations. However in cases where there are chronically high carbon dioxide levels in the blood such as in COPD patients, the body will begin to rely more on the oxygen receptors and less on the carbon dioxide receptors. In this case, when there is an increase in oxygen levels, the body will decrease the respirations. If a person with chronic hypoxic drive enters acute respiratory distress, healthcare providers who are unaware of their condition may provide oxygen therapy as an initial treatment. The reaction to increased oxygen causes the oxygen receptors to decrease respirations, possibly to the point of respiratory arrest. For this reason, people with hypoxic drive must not receive oxygen in high concentrations or for long periods. Treatment of a patient in acute respiratory distress with hypoxic drive can still be given oxygen therapy, however to avoid having the situation deteriorate to full respiratory arrest, arterial blood gas levels should be closely monitored via pulse oximetry and respirations should also be closely monitored. # See Also - Respiratory System - Homeostasis Normal respiration is driven mostly by the levels of carbon dioxide in the blood, which are detected by central chemoreceptors, via a change in pH. It has very little by the oxygen levels. An increase in carbon dioxide will cause chemoreceptor reflexes to trigger an increase in respirations. # External Links - The Hypoxic Drive - Anaesthia Explained	https://www.wikidoc.org/index.php/Hypoxic_drive
1a7a73e60423fb4f266bb2813f133fb75bdc8369	wikidoc	Hysteresivity	Hysteresivity # Overview “Hysteresivity” derives from “hysteresis”, meaning “lag”. It is the tendency to react slowly to an outside force, or to not return completely to its original state. Whereas the area within a hysteresis loop represents energy dissipated to heat and is an extensive quantity with units of energy, the hysteresivity represents the fraction of the elastic energy that is lost to heat, and is an intensive property that is dimensionless. When a force deforms a material it generates internal elastic stresses and internal frictional stresses. Most often, frictional stress is described as being analogous to the stress that results from the flow of a viscous fluid, but in many engineering materials, in soft biological tissues, and in living cells, the concept that friction arises only from a viscous stress is now known to be erroneous (3, 9). For example, Bayliss and Robertson (1) and Hildebrandt (12) demonstrated that frictional stress in lung tissue is dependent upon the amount of lung expansion but not the rate of expansion, findings that are fundamentally incompatible with the notion of friction being caused by a viscous stress. If not by a viscous stress, how then does friction arise, and how is it properly described? In many inert and living materials, the relationship between elastic and frictional stresses turns out to be very nearly invariant (something unaltered by a transformation). In lung tissues, for example, the frictional stress is almost invariably between 0.1 and 0.2 of the elastic stress, where this fraction is called the hysteresivity, h, or, equivalently, the structural damping coefficient (9). It is a simple phenomenological fact, therefore, that for each unit of peak elastic strain energy that is stored during a cyclic deformation, 10 to 20 % of that elastic energy is taxed as friction and lost irreversibly to heat. This fixed relationship holds at the level of the whole lung (11, 14), isolated lung parenchymal tissue strips (7), isolated smooth muscle strips (8, 9), and even isolated living cells (2, 4-6). This close relationship between frictional and elastic stresses is called the structural damping law (3, 9, 10, 12) or, sometimes, the constant phase model (11). The structural damping law implies that frictional losses are coupled tightly to elastic stresses rather than to viscous stresses, but the precise molecular mechanical origin of this phenomenon remains unknown (2, 13). In material science, the complex elastic modulus of a material, G(f), at frequency of oscillatory deformation, f, is given by, \ G^{}(f)=G^{'}+jG^{} where: - G(f)= complex elastic modulus at frequency of oscillatory deformation, f - G’ = the elastic modulus - G” = the loss modulus - j^^2 = -1 This relationship can be rewritten as, \ G^{}(f)=G^{'}(1 + jh) where: - h = G”/G’. In systems conforming to the structural damping law, the hysteresivity "h" is constant with or insensitive to changes in oscillatory frequency], and the loss modulus G” (= h G’) becomes a constant fraction of the elastic modulus.	Hysteresivity Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview “Hysteresivity” derives from “hysteresis”, meaning “lag”. It is the tendency to react slowly to an outside force, or to not return completely to its original state. Whereas the area within a hysteresis loop represents energy dissipated to heat and is an extensive quantity with units of energy, the hysteresivity represents the fraction of the elastic energy that is lost to heat, and is an intensive property that is dimensionless. When a force deforms a material it generates internal elastic stresses and internal frictional stresses. Most often, frictional stress is described as being analogous to the stress that results from the flow of a viscous fluid, but in many engineering materials, in soft biological tissues, and in living cells, the concept that friction arises only from a viscous stress is now known to be erroneous (3, 9). For example, Bayliss and Robertson (1) and Hildebrandt (12) demonstrated that frictional stress in lung tissue is dependent upon the amount of lung expansion but not the rate of expansion, findings that are fundamentally incompatible with the notion of friction being caused by a viscous stress. If not by a viscous stress, how then does friction arise, and how is it properly described? In many inert and living materials, the relationship between elastic and frictional stresses turns out to be very nearly invariant (something unaltered by a transformation). In lung tissues, for example, the frictional stress is almost invariably between 0.1 and 0.2 of the elastic stress, where this fraction is called the hysteresivity, h, or, equivalently, the structural damping coefficient (9). It is a simple phenomenological fact, therefore, that for each unit of peak elastic strain energy that is stored during a cyclic deformation, 10 to 20 % of that elastic energy is taxed as friction and lost irreversibly to heat. This fixed relationship holds at the level of the whole lung (11, 14), isolated lung parenchymal tissue strips (7), isolated smooth muscle strips (8, 9), and even isolated living cells (2, 4-6). This close relationship between frictional and elastic stresses is called the structural damping law (3, 9, 10, 12) or, sometimes, the constant phase model (11). The structural damping law implies that frictional losses are coupled tightly to elastic stresses rather than to viscous stresses, but the precise molecular mechanical origin of this phenomenon remains unknown (2, 13). In material science, the complex elastic modulus of a material, G(f), at frequency of oscillatory deformation, f, is given by, <math>\ G^{}(f)=G^{'}+jG^{} </math> where: - G(f)= complex elastic modulus at frequency of oscillatory deformation, f - G’ = the elastic modulus - G” = the loss modulus - j^^2 = -1 This relationship can be rewritten as, <math>\ G^{}(f)=G^{'}(1 + jh) </math> where: - h = G”/G’. In systems conforming to the structural damping law, the hysteresivity "h" is constant with or insensitive to changes in oscillatory frequency], and the loss modulus G” (= h G’) becomes a constant fraction of the elastic modulus.	https://www.wikidoc.org/index.php/Hysteresivity
7a44a097c00a0e2da57ab6f9c99d583b20905c84	wikidoc	Interleukin 2	Interleukin 2 Interleukin-2 (IL-2) is an interleukin, a type of cytokine signaling molecule in the immune system. It is a 15,5 - 16 kDa protein that regulates the activities of white blood cells (leukocytes, often lymphocytes) that are responsible for immunity. IL-2 is part of the body's natural response to microbial infection, and in discriminating between foreign ("non-self") and "self". IL-2 mediates its effects by binding to IL-2 receptors, which are expressed by lymphocytes. # Signaling pathway IL-2 is a member of a cytokine family, each member of which has a four alpha helix bundle; the family also includes IL-4, IL-7, IL-9, IL-15 and IL-21. IL-2 signals through the IL-2 receptor, a complex consisting of three chains, termed alpha, beta and gamma. The gamma chain is shared by all family members. The IL-2 Receptor (IL-2R) α subunit has low affinity for its ligand but has the ability (when bound to the β and ϒ subunit) to increase the IL-2R affinity 100-fold. Heterodimerization of the β and ϒ subunits of IL-2R is essential for signalling in T cells. Gene expression regulation for IL-2 can be on multiple levels or by different ways. One of the checkpoints is signaling through TCR receptor, antigen receptor of T-lymphocytes after recognizing MHC-peptide complex. Signaling pathway from TCR then goes through phospholipase-C (PLC) dependent pathway. PLC activates 3 major transcription factors and their pathways: NFAT, NFkB and AP-1. After costimulation from CD28 the optimal activation of expression of IL-2 and these pathways is induced. At the same time Oct-1 is expressed. It helps the activation. Oct1 is expressed in T-lymphocytes and Oct2 is induced after cell activation. NFAT has multiple family members, all of them are located in cytoplasm and signaling goes through calcineurin, NFAT is dephosphorylated and therefore translocated to the nucleus. AP-1 is a dimer and is composed of c-Jun and c-Fos proteins. It cooperates with other transcription factors including NFkB and Oct. NFkB is translocated to the nucleus after costimulation through CD28. NFkB is a heterodimer and there are two binding sites on the IL-2 promoter. # Function IL-2 has essential roles in key functions of the immune system, tolerance and immunity, primarily via its direct effects on T cells. In the thymus, where T cells mature, it prevents autoimmune diseases by promoting the differentiation of certain immature T cells into regulatory T cells, which suppress other T cells that are otherwise primed to attack normal healthy cells in the body. IL-2 also promotes the differentiation of T cells into effector T cells and into memory T cells when the initial T cell is also stimulated by an antigen, thus helping the body fight off infections. Its expression and secretion is tightly regulated and functions as part of both transient positive and negative feedback loops in mounting and dampening immune responses. Through its role in the development of T cell immunologic memory, which depends upon the expansion of the number and function of antigen-selected T cell clones, it plays a key role in enduring cell-mediated immunity. # Role in disease While the causes of itchiness are poorly understood, some evidence indicates that IL-2 is involved in itchy psoriasis. # Medical use ## Pharmaceutical analogues Aldesleukin is a form of recombinant interleukin-2. It is manufactured using recombinant DNA technology and is marketed as a protein therapeutic and branded as Proleukin. It has been approved by the Food and Drug Administration (FDA) and in several European countries for the treatment of cancers (malignant melanoma, renal cell cancer) in large intermittent doses and has been extensively used in continuous doses. Interking is a recombinant IL-2 with a serine at residue 125, sold by Shenzhen Neptunus. Neoleukin 2/15 is a computationally designed mimic of IL-2 that was designed to avoid common side effects. It it currently being commercialized into a therapeutic. ### Dosage Various dosages of IL-2 across the United States and across the world are used. The efficiency and side effects of different dosages is often a point of disagreement. Usually, in the U.S., the higher dosage option is used, affected by cancer type, response to treatment and general patient health. Patients are typically treated for five consecutive days, three times a day, for fifteen minutes. The following approximately 10 days help the patient to recover between treatments. IL-2 is delivered intravenously on an inpatient basis to enable proper monitoring of side effects. A lower dose regimen involves injection of IL-2 under the skin typically on an outpatient basis. It may alternatively be given on an inpatient basis over 1–3 days, similar to and often including the delivery of chemotherapy. Intralesional IL-2 is commonly used to treat in-transit melanoma metastases and has a high complete response rate. ### Toxicity IL-2 has a narrow therapeutic window, and the level of dosing usually determines the severity of the side effects. Some common side effects: - flu-like symptoms (fever, headache, muscle and joint pain, fatigue) - nausea/vomiting - dry, itchy skin or rash - weakness or shortness of breath - diarrhea - low blood pressure - drowsiness or confusion - loss of appetite More serious and dangerous side effects sometimes are seen, such as capillary leak syndrome, breathing problems, serious infections, seizures, allergic reactions, heart problems or a variety of other possible complications. Intralesional IL-2 used to treat in-transit melanoma metastases is generally well-tolerated. ## Pharmaceutical derivative Eisai markets a drug called denileukin diftitox (trade name Ontak), which is a recombinant fusion protein of the human IL-2 ligand and the diphtheria toxin. This drug binds to IL-2 receptors and introduces the diphtheria toxin into cells that express those receptors, killing the cells. In some leukemias and lymphomas, malignant cells express the IL-2 receptor, so denileukin diftitox can kill them. In 1999 Ontak was approved by the U.S. Food and Drug Administration (FDA) for treatment of cutaneous T-cell Lymphoma (CTCL). # Clinical research IL-2 has been used in clinical trials for the treatment of chronic viral infections and as a booster (adjuvant) for vaccines. The use of large doses of IL-2 given every 6–8 weeks in HIV therapy, similar to its use in cancer therapy, was found to be ineffective in preventing progression to an AIDS diagnosis in two large clinical trials published in 2009. More recently low dose IL-2 has shown early success in modulating the immune system in disease like type 1 diabetes and vasculitis. There are also promising studies looking to use low dose IL-2 in ischaemic heart disease. # History According to an immunology textbook: "IL-2 is particularly important historically, as it is the first type I cytokine that was cloned, the first type I cytokine for which a receptor component was cloned, and was the first short-chain type I cytokine whose receptor structure was solved. Many general principles have been derived from studies of this cytokine including its being the first cytokine demonstrated to act in a growth factor–like fashion through specific high-affinity receptors, analogous to the growth factors being studied by endocrinologists and biochemists".:712 In the mid-1960s, studies reported "activities" in leukocyte-conditioned media that promoted lymphocyte proliferation.:16 In the mid-1970s, it was discovered that T-cells could be selectively proliferated when normal human bone marrow cells were cultured in conditioned medium obtained from phytohemagglutinin-stimulated normal human lymphocytes.:712 The key factor was isolated from cultured mouse cells in 1979 and from cultured human cells in 1980. The gene for human IL-2 was cloned in 1982 after an intense competition.:76 Commercial activity to bring an IL-2 drug to market was intense in the 1980s and '90s. By 1983, Cetus Corporation had created a proprietary recombinant version of IL-2 (Aldesleukin, later branded as Proleukin), with the alanine removed from its N-terminal and residue 125 replaced with serine.:76–77:201 Amgen later entered the field with its own proprietary, mutated, recombinant protein and Cetus and Amgen were soon competing scientifically and in the courts; Cetus won the legal battles and forced Amgen out of the field.:151 By 1990 Cetus had gotten aldesleukin approved in nine European countries but in that year, the U.S. Food and Drug Administration (FDA) refused to approve Cetus' application to market IL-2. The failure led to the collapse of Cetus, and in 1991 the company was sold to Chiron Corporation. Chiron continued the development of IL-2, which was finally approved by the FDA as Proleukin for metastatic renal carcinoma in 1992. By 1993 aldesleukin was the only approved version of IL-2, but Roche was also developing a proprietary, modified, recombinant IL-2 called teceleukin, with a methionine added at is N-terminal, and Glaxo was developing a version called bioleukin, with a methionine added at is N-terminal and residue 125 replaced with alanine. Dozens of clinical trials had been conducted of recombinant or purified IL-2, alone, in combination with other drugs, or using cell therapies, in which cells were taken from patients, activated with IL-2, then reinfused. Novartis acquired Chiron in 2006 and sold the aldesleukin business to Prometheus Laboratories in 2010.	Interleukin 2 Interleukin-2 (IL-2) is an interleukin, a type of cytokine signaling molecule in the immune system. It is a 15,5 - 16 kDa protein[1] that regulates the activities of white blood cells (leukocytes, often lymphocytes) that are responsible for immunity. IL-2 is part of the body's natural response to microbial infection, and in discriminating between foreign ("non-self") and "self". IL-2 mediates its effects by binding to IL-2 receptors, which are expressed by lymphocytes. # Signaling pathway IL-2 is a member of a cytokine family, each member of which has a four alpha helix bundle; the family also includes IL-4, IL-7, IL-9, IL-15 and IL-21. IL-2 signals through the IL-2 receptor, a complex consisting of three chains, termed alpha, beta and gamma. The gamma chain is shared by all family members.[2] The IL-2 Receptor (IL-2R) α subunit has low affinity for its ligand but has the ability (when bound to the β and ϒ subunit) to increase the IL-2R affinity 100-fold. Heterodimerization of the β and ϒ subunits of IL-2R is essential for signalling in T cells.[3][3] Gene expression regulation for IL-2 can be on multiple levels or by different ways. One of the checkpoints is signaling through TCR receptor, antigen receptor of T-lymphocytes after recognizing MHC-peptide complex. Signaling pathway from TCR then goes through phospholipase-C (PLC) dependent pathway. PLC activates 3 major transcription factors and their pathways: NFAT, NFkB and AP-1. After costimulation from CD28 the optimal activation of expression of IL-2 and these pathways is induced. At the same time Oct-1 is expressed. It helps the activation. Oct1 is expressed in T-lymphocytes and Oct2 is induced after cell activation. NFAT has multiple family members, all of them are located in cytoplasm and signaling goes through calcineurin, NFAT is dephosphorylated and therefore translocated to the nucleus. AP-1 is a dimer and is composed of c-Jun and c-Fos proteins. It cooperates with other transcription factors including NFkB and Oct. NFkB is translocated to the nucleus after costimulation through CD28. NFkB is a heterodimer and there are two binding sites on the IL-2 promoter. # Function IL-2 has essential roles in key functions of the immune system, tolerance and immunity, primarily via its direct effects on T cells. In the thymus, where T cells mature, it prevents autoimmune diseases by promoting the differentiation of certain immature T cells into regulatory T cells, which suppress other T cells that are otherwise primed to attack normal healthy cells in the body. IL-2 also promotes the differentiation of T cells into effector T cells and into memory T cells when the initial T cell is also stimulated by an antigen, thus helping the body fight off infections.[2] Its expression and secretion is tightly regulated and functions as part of both transient positive and negative feedback loops in mounting and dampening immune responses. Through its role in the development of T cell immunologic memory, which depends upon the expansion of the number and function of antigen-selected T cell clones, it plays a key role in enduring cell-mediated immunity.[2][4] # Role in disease While the causes of itchiness are poorly understood, some evidence indicates that IL-2 is involved in itchy psoriasis.[5] # Medical use ## Pharmaceutical analogues Aldesleukin is a form of recombinant interleukin-2. It is manufactured using recombinant DNA technology and is marketed as a protein therapeutic and branded as Proleukin. It has been approved by the Food and Drug Administration (FDA) and in several European countries for the treatment of cancers (malignant melanoma, renal cell cancer) in large intermittent doses and has been extensively used in continuous doses.[6][7][8] Interking is a recombinant IL-2 with a serine at residue 125, sold by Shenzhen Neptunus.[9] Neoleukin 2/15 is a computationally designed mimic of IL-2 that was designed to avoid common side effects.[10] It it currently being commercialized into a therapeutic.[11] ### Dosage Various dosages of IL-2 across the United States and across the world are used. The efficiency and side effects of different dosages is often a point of disagreement. Usually, in the U.S., the higher dosage option is used, affected by cancer type, response to treatment and general patient health. Patients are typically treated for five consecutive days, three times a day, for fifteen minutes. The following approximately 10 days help the patient to recover between treatments. IL-2 is delivered intravenously on an inpatient basis to enable proper monitoring of side effects.[12] A lower dose regimen involves injection of IL-2 under the skin typically on an outpatient basis. It may alternatively be given on an inpatient basis over 1–3 days, similar to and often including the delivery of chemotherapy.[12] Intralesional IL-2 is commonly used to treat in-transit melanoma metastases and has a high complete response rate.[13] ### Toxicity IL-2 has a narrow therapeutic window, and the level of dosing usually determines the severity of the side effects.[14] Some common side effects:[12] - flu-like symptoms (fever, headache, muscle and joint pain, fatigue) - nausea/vomiting - dry, itchy skin or rash - weakness or shortness of breath - diarrhea - low blood pressure - drowsiness or confusion - loss of appetite More serious and dangerous side effects sometimes are seen, such as capillary leak syndrome, breathing problems, serious infections, seizures, allergic reactions, heart problems or a variety of other possible complications.[12] Intralesional IL-2 used to treat in-transit melanoma metastases is generally well-tolerated.[13] ## Pharmaceutical derivative Eisai markets a drug called denileukin diftitox (trade name Ontak), which is a recombinant fusion protein of the human IL-2 ligand and the diphtheria toxin.[15] This drug binds to IL-2 receptors and introduces the diphtheria toxin into cells that express those receptors, killing the cells. In some leukemias and lymphomas, malignant cells express the IL-2 receptor, so denileukin diftitox can kill them. In 1999 Ontak was approved by the U.S. Food and Drug Administration (FDA) for treatment of cutaneous T-cell Lymphoma (CTCL).[16] # Clinical research IL-2 has been used in clinical trials for the treatment of chronic viral infections and as a booster (adjuvant) for vaccines. The use of large doses of IL-2 given every 6–8 weeks in HIV therapy, similar to its use in cancer therapy, was found to be ineffective in preventing progression to an AIDS diagnosis in two large clinical trials published in 2009.[17] More recently low dose IL-2 has shown early success in modulating the immune system in disease like type 1 diabetes and vasculitis.[18] There are also promising studies looking to use low dose IL-2 in ischaemic heart disease.[19] # History According to an immunology textbook: "IL-2 is particularly important historically, as it is the first type I cytokine that was cloned, the first type I cytokine for which a receptor component was cloned, and was the first short-chain type I cytokine whose receptor structure was solved. Many general principles have been derived from studies of this cytokine including its being the first cytokine demonstrated to act in a growth factor–like fashion through specific high-affinity receptors, analogous to the growth factors being studied by endocrinologists and biochemists".[20]:712 In the mid-1960s, studies reported "activities" in leukocyte-conditioned media that promoted lymphocyte proliferation.[21]:16 In the mid-1970s, it was discovered that T-cells could be selectively proliferated when normal human bone marrow cells were cultured in conditioned medium obtained from phytohemagglutinin-stimulated normal human lymphocytes.[20]:712 The key factor was isolated from cultured mouse cells in 1979 and from cultured human cells in 1980.[22] The gene for human IL-2 was cloned in 1982 after an intense competition.[23]:76 Commercial activity to bring an IL-2 drug to market was intense in the 1980s and '90s. By 1983, Cetus Corporation had created a proprietary recombinant version of IL-2 (Aldesleukin, later branded as Proleukin), with the alanine removed from its N-terminal and residue 125 replaced with serine.[23]:76–77[24]:201[25] Amgen later entered the field with its own proprietary, mutated, recombinant protein and Cetus and Amgen were soon competing scientifically and in the courts; Cetus won the legal battles and forced Amgen out of the field.[23]:151 By 1990 Cetus had gotten aldesleukin approved in nine European countries but in that year, the U.S. Food and Drug Administration (FDA) refused to approve Cetus' application to market IL-2.[8] The failure led to the collapse of Cetus, and in 1991 the company was sold to Chiron Corporation.[26][27] Chiron continued the development of IL-2, which was finally approved by the FDA as Proleukin for metastatic renal carcinoma in 1992.[28] By 1993 aldesleukin was the only approved version of IL-2, but Roche was also developing a proprietary, modified, recombinant IL-2 called teceleukin, with a methionine added at is N-terminal, and Glaxo was developing a version called bioleukin, with a methionine added at is N-terminal and residue 125 replaced with alanine. Dozens of clinical trials had been conducted of recombinant or purified IL-2, alone, in combination with other drugs, or using cell therapies, in which cells were taken from patients, activated with IL-2, then reinfused.[25][29] Novartis acquired Chiron in 2006[30] and sold the aldesleukin business to Prometheus Laboratories in 2010.[31]	https://www.wikidoc.org/index.php/IL-2
6bbde9aa2db875f18415f6b30e977230d664332e	wikidoc	Interleukin 4	Interleukin 4 The interleukin 4 (IL4, IL-4) is a cytokine that induces differentiation of naive helper T cells (Th0 cells) to Th2 cells. Upon activation by IL-4, Th2 cells subsequently produce additional IL-4 in a positive feedback loop. The cell that initially produces IL-4, thus inducing Th2 differentiation, has not been identified, but recent studies suggest that basophils may be the effector cell. It is closely related and has functions similar to Interleukin 13. # Function Interleukin 4 has many biological roles, including the stimulation of activated B-cell and T-cell proliferation, and the differentiation of B cells into plasma cells. It is a key regulator in humoral and adaptive immunity. IL-4 induces B-cell class switching to IgE, and up-regulates MHC class II production. IL-4 decreases the production of Th1 cells, macrophages, IFN-gamma, and dendritic cell IL-12. Overproduction of IL-4 is associated with allergies. ## Inflammation and wound repair Tissue macrophages play an important role in chronic inflammation and wound repair. The presence of IL-4 in extravascular tissues promotes alternative activation of macrophages into M2 cells and inhibits classical activation of macrophages into M1 cells. An increase in repair macrophages (M2) is coupled with secretion of IL-10 and TGF-β that result in a diminution of pathological inflammation. Release of arginase, proline, polyaminases and TGF-β by the activated M2 cell is tied with wound repair and fibrosis. # Receptor The receptor for Interleukin-4 is known as the IL-4Rα. This receptor exists in 3 different complexes throughout the body. Type 1 receptors are composed of the IL-4Rα subunit with a common γ chain and specifically bind IL-4. Type 2 receptors consist of an IL-4Rα subunit bound to a different subunit known as IL-13Rα1. These type 2 receptors have the ability to bind both IL-4 and IL-13, two cytokines with closely related biological functions. # Structure IL-4 has a compact, globular fold (similar to other cytokines), stabilised by 3 disulphide bonds. One half of the structure is dominated by a 4 alpha-helix bundle with a left-handed twist. The helices are anti-parallel, with 2 overhand connections, which fall into a 2-stranded anti-parallel beta-sheet. # Discovery This cytokine was co-discovered by Maureen Howard and William E. Paul as well as by Ellen Vitetta and her research group in 1982. The nucleotide sequence for human IL-4 was isolated four years later confirming its similarity to a mouse protein called B-cell stimulatory factor-1 (BCSF-1). # Animal studies IL-4 has been found to mediate a crosstalk between the neural stem cells and neurons that undergo neurodegeneration, and initiate a regeneration cascade through phosphorylation of its intracellular effector STAT6 in an experimental Alzheimer's disease model in adult zebrafish brain. # Clinical significance IL-4 also has been shown to drive mitogenesis, dedifferentiation, and metastasis in rhabdomyosarcoma. IL-4, along with other Th2 cytokines, is involved in the airway inflammation observed in the lungs of patients with allergic asthma. # Illnesses associated with IL-4 IL-4 plays an important role in the development of certain immune disorders, particularly allergies and some autoimmune diseases. ## Allergic diseases Allergic diseases are sets of disorders that are manifested by a disproportionate response of the immune system to the allergen and Th2 responses. These pathologies include, for example, atopic dermatitis, asthma, or systemic anaphylaxis. Interleukin 4 mediates important pro-inflammatory functions in asthma, including induction of isotype rearrangement of IgE, expression of VCAM-1 molecules (vascular cell adhesion molecule 1), promoting eosinophilic transmigration through endothelium, mucus secretion and T helper type 2 (Th2) leading to cytokine release. Asthma is a complex genetic disorder that has been associated with IL-4 gene promoter polymorphism and proteins involved in IL-4 signaling. ## Tumors IL-4 has a significant effect on tumor progression. Increased IL-4 production was found in breast, prostate, lung, renal cells and other types of cancer. Many overexpression of IL-4R has been found in many types of cancer. Renal cells and glioblastoma modify 10,000-13,000 receptors per cell depending on tumor type. IL-4 can primitively motivate tumor cells and increase their apoptosis resistance by increasing tumor growth. ## Nervous system Brain tissue tumors such as astrocytoma, glioblastoma, meningioma, and medulloblastoma overexpress receptors for various growth factors including epidermal growth factor receptor, FGFR-1 (fibroblast growth factor receptor 1), TfR angiotensin transferrin receptor), IL-13R. Most human meningiomas massively expresses IL-4 receptors, indicating its role in cancer progression. They express IL-4Rα and IL13Rα-1-1, but not the surface γc chain, suggesting that most human meningiomas express IL-4 type II. ## HIV IL-4 may also play a role in the infection and development of HIV disease. Auxiliary T-lymphocytes are a key element of HIV-1 infection. Several signs of immune dysregulation such as polyclonal B-cell initialization, previous cell-mediated antigen-induced response and hypergammaglobulinaemia occur in most HIV-1 infected patients and are associated with cytokines synthesized by Th2 cells. Increased IL-4 production by Th2 cells has been demonstrated in people infected with HIV.	Interleukin 4 The interleukin 4 (IL4, IL-4) is a cytokine that induces differentiation of naive helper T cells (Th0 cells) to Th2 cells. Upon activation by IL-4, Th2 cells subsequently produce additional IL-4 in a positive feedback loop. The cell that initially produces IL-4, thus inducing Th2 differentiation, has not been identified, but recent studies suggest that basophils may be the effector cell.[1] It is closely related and has functions similar to Interleukin 13. # Function Interleukin 4 has many biological roles, including the stimulation of activated B-cell and T-cell proliferation, and the differentiation of B cells into plasma cells. It is a key regulator in humoral and adaptive immunity. IL-4 induces B-cell class switching to IgE, and up-regulates MHC class II production. IL-4 decreases the production of Th1 cells, macrophages, IFN-gamma, and dendritic cell IL-12. Overproduction of IL-4 is associated with allergies.[2] ## Inflammation and wound repair Tissue macrophages play an important role in chronic inflammation and wound repair. The presence of IL-4 in extravascular tissues promotes alternative activation of macrophages into M2 cells and inhibits classical activation of macrophages into M1 cells. An increase in repair macrophages (M2) is coupled with secretion of IL-10 and TGF-β that result in a diminution of pathological inflammation. Release of arginase, proline, polyaminases and TGF-β by the activated M2 cell is tied with wound repair and fibrosis.[3] # Receptor The receptor for Interleukin-4 is known as the IL-4Rα. This receptor exists in 3 different complexes throughout the body. Type 1 receptors are composed of the IL-4Rα subunit with a common γ chain and specifically bind IL-4. Type 2 receptors consist of an IL-4Rα subunit bound to a different subunit known as IL-13Rα1. These type 2 receptors have the ability to bind both IL-4 and IL-13, two cytokines with closely related biological functions.[4][5] # Structure IL-4 has a compact, globular fold (similar to other cytokines), stabilised by 3 disulphide bonds.[6] One half of the structure is dominated by a 4 alpha-helix bundle with a left-handed twist.[7] The helices are anti-parallel, with 2 overhand connections, which fall into a 2-stranded anti-parallel beta-sheet.[7] # Discovery This cytokine was co-discovered by Maureen Howard and William E. Paul[8] as well as by Ellen Vitetta and her research group in 1982. The nucleotide sequence for human IL-4 was isolated four years later confirming its similarity to a mouse protein called B-cell stimulatory factor-1 (BCSF-1).[9] # Animal studies IL-4 has been found to mediate a crosstalk between the neural stem cells and neurons that undergo neurodegeneration, and initiate a regeneration cascade through phosphorylation of its intracellular effector STAT6 in an experimental Alzheimer's disease model in adult zebrafish brain.[10] # Clinical significance IL-4 also has been shown to drive mitogenesis, dedifferentiation, and metastasis in rhabdomyosarcoma.[11] IL-4, along with other Th2 cytokines, is involved in the airway inflammation observed in the lungs of patients with allergic asthma.[12] # Illnesses associated with IL-4 IL-4 plays an important role in the development of certain immune disorders, particularly allergies and some autoimmune diseases. ## Allergic diseases Allergic diseases are sets of disorders that are manifested by a disproportionate response of the immune system to the allergen and Th2 responses. These pathologies include, for example, atopic dermatitis, asthma, or systemic anaphylaxis. Interleukin 4 mediates important pro-inflammatory functions in asthma, including induction of isotype rearrangement of IgE, expression of VCAM-1 molecules (vascular cell adhesion molecule 1), promoting eosinophilic transmigration through endothelium, mucus secretion and T helper type 2 (Th2) leading to cytokine release. Asthma is a complex genetic disorder that has been associated with IL-4 gene promoter polymorphism and proteins involved in IL-4 signaling.[13] ## Tumors IL-4 has a significant effect on tumor progression. Increased IL-4 production was found in breast, prostate, lung, renal cells and other types of cancer. Many overexpression of IL-4R has been found in many types of cancer. Renal cells and glioblastoma modify 10,000-13,000 receptors per cell depending on tumor type.[14] IL-4 can primitively motivate tumor cells and increase their apoptosis resistance by increasing tumor growth.[15] ## Nervous system Brain tissue tumors such as astrocytoma, glioblastoma, meningioma, and medulloblastoma overexpress receptors for various growth factors including epidermal growth factor receptor, FGFR-1 (fibroblast growth factor receptor 1), TfR angiotensin transferrin receptor), IL-13R. Most human meningiomas massively expresses IL-4 receptors, indicating its role in cancer progression. They express IL-4Rα and IL13Rα-1-1, but not the surface γc chain, suggesting that most human meningiomas express IL-4 type II.[16] ## HIV IL-4 may also play a role in the infection and development of HIV disease. Auxiliary T-lymphocytes are a key element of HIV-1 infection. Several signs of immune dysregulation such as polyclonal B-cell initialization, previous cell-mediated antigen-induced response and hypergammaglobulinaemia occur in most HIV-1 infected patients and are associated with cytokines synthesized by Th2 cells. Increased IL-4 production by Th2 cells has been demonstrated in people infected with HIV.[17]	https://www.wikidoc.org/index.php/IL-4
36a3ab8e95c4484100508e287b0afdfffc0b04f1	wikidoc	Interleukin 5	Interleukin 5 Interleukin 5 (IL5) is an interleukin produced by type-2 T helper cells and mast cells. # Function Through binding to the interleukin-5 receptor, interleukin 5 stimulates B cell growth and increases immunoglobulin secretion - primarily IgA. It is also a key mediator in eosinophil activation. # Structure IL-5 is a 115-amino acid (in human, 133 in the mouse) -long TH2 cytokine that is part of the hematopoietic family. Unlike other members of this cytokine family (namely interleukin 3 and GM-CSF), this glycoprotein in its active form is a homodimer. # Tissue expression The IL-5 gene is located on chromosome 11 in the mouse, and chromosome 5 in humans, in close proximity to the genes encoding IL-3, IL-4, and granulocyte-macrophage colony-stimulating factor (GM-CSF), which are often co-expressed in TH2 cells. Interleukin-5 is also expressed by eosinophils and has been observed in the mast cells of asthmatic airways by immunohistochemistry. IL-5 expression is regulated by several transcription factors including GATA3. # Clinical significance Interleukin-5 has long been associated with the cause of several allergic diseases including allergic rhinitis and asthma, wherein a large increase in the number of circulating, airway tissue, and induced sputum eosinophils have been observed. Given the high concordance of eosinophils and, in particular, allergic asthma pathology, it has been widely speculated that eosinophils have an important role in the pathology of this disease. Drugs that target IL-5 are mepolizumab and reslizumab. # Effect on eosinophils Eosinophils are terminally differentiated granulocytes found in most mammals. The principal role of these cells, in a healthy host, is the elimination of antibody bound parasites through the release of cytotoxic granule proteins. Given that eosinophils are the primary IL-5Rα-expressing cells, it is not surprising that this cell type responds to IL-5. In fact, IL-5 was originally discovered as an eosinophil colony-stimulating factor, is a major regulator of eosinophil accumulation in tissues, and can modulate eosinophil behavior at every stage from maturation to survival. Mepolizumab is a monoclonal antibody against IL-5 which can reduce excessive eosinophilia. In Hodgkin lymphoma, for instance, the typically-observed eosinophilia is thought to be attributable to an increased production of IL-5. # Interactions Interleukin 5 has been shown to interact with Interleukin 5 receptor alpha subunit. # Receptors The IL-5 receptor is composed of an α and a βc chain. The α subunit is specific for the IL-5 molecule, whereas the βc subunit also recognised by interleukin 3 (IL3) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Glycosylation of the Asn196 residue of the Rα subunit appears to be essential for binding of IL-5.	Interleukin 5 Interleukin 5 (IL5) is an interleukin produced by type-2 T helper cells and mast cells. # Function Through binding to the interleukin-5 receptor, interleukin 5 stimulates B cell growth and increases immunoglobulin secretion - primarily IgA. It is also a key mediator in eosinophil activation. # Structure IL-5 is a 115-amino acid (in human, 133 in the mouse) -long TH2 cytokine that is part of the hematopoietic family. Unlike other members of this cytokine family (namely interleukin 3 and GM-CSF), this glycoprotein in its active form is a homodimer.[1] # Tissue expression The IL-5 gene is located on chromosome 11 in the mouse, and chromosome 5 in humans, in close proximity to the genes encoding IL-3, IL-4, and granulocyte-macrophage colony-stimulating factor (GM-CSF),[2][3] which are often co-expressed in TH2 cells. Interleukin-5 is also expressed by eosinophils[4] and has been observed in the mast cells of asthmatic airways by immunohistochemistry.[5] IL-5 expression is regulated by several transcription factors including GATA3.[6] # Clinical significance Interleukin-5 has long been associated with the cause of several allergic diseases including allergic rhinitis and asthma, wherein a large increase in the number of circulating, airway tissue, and induced sputum eosinophils have been observed.[7] Given the high concordance of eosinophils and, in particular, allergic asthma pathology, it has been widely speculated that eosinophils have an important role in the pathology of this disease.[8] Drugs that target IL-5 are mepolizumab and reslizumab. # Effect on eosinophils Eosinophils are terminally differentiated granulocytes found in most mammals. The principal role of these cells, in a healthy host, is the elimination of antibody bound parasites through the release of cytotoxic granule proteins.[9] Given that eosinophils are the primary IL-5Rα-expressing cells, it is not surprising that this cell type responds to IL-5. In fact, IL-5 was originally discovered as an eosinophil colony-stimulating factor,[10] is a major regulator of eosinophil accumulation in tissues, and can modulate eosinophil behavior at every stage from maturation to survival. Mepolizumab is a monoclonal antibody against IL-5 which can reduce excessive eosinophilia. In Hodgkin lymphoma, for instance, the typically-observed eosinophilia is thought to be attributable to an increased production of IL-5.[11] # Interactions Interleukin 5 has been shown to interact with Interleukin 5 receptor alpha subunit.[12][13][14] # Receptors The IL-5 receptor is composed of an α and a βc chain.[15] The α subunit is specific for the IL-5 molecule, whereas the βc subunit also recognised by interleukin 3 (IL3) and granulocyte-macrophage colony-stimulating factor (GM-CSF).[15][16] Glycosylation of the Asn196 residue of the Rα subunit appears to be essential for binding of IL-5.[17]	https://www.wikidoc.org/index.php/IL-5
def85c935b13e40f2c2079eef471ed0bb045b20b	wikidoc	Interleukin 6	Interleukin 6 Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the IL6 gene. In addition, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smooth muscle cells in the tunica media of many blood vessels also produce IL-6 as a pro-inflammatory cytokine. IL-6's role as an anti-inflammatory myokine is mediated through its inhibitory effects on TNF-alpha and IL-1, and activation of IL-1ra and IL-10. # Function - IL-6 is an important mediator of fever and of the acute phase response. - It is capable of crossing the blood-brain barrier and initiating synthesis of PGE2 in the hypothalamus, thereby changing the body's temperature setpoint. - In muscle and fatty tissue, IL-6 stimulates energy mobilization that leads to increased body temperature. - IL-6 can be secreted by macrophages in response to specific microbial molecules, referred to as pathogen-associated molecular patterns (PAMPs). These PAMPs bind to an important group of detection molecules of the innate immune system, called pattern recognition receptors (PRRs), including Toll-like receptors (TLRs). These are present on the cell surface and intracellular compartments and induce intracellular signaling cascades that give rise to inflammatory cytokine production. - IL-6 is found in many supplemental cloning media such as briclone. - Inhibitors of IL-6 (including estrogen) are used to treat postmenopausal osteoporosis. - IL-6 is also produced by adipocytes and is thought to be a reason why obese individuals have higher endogeneous levels of CRP. - Intranasally administered IL-6 has been shown to improve sleep-associated consolidation of emotional memories. - IL-6 is responsible for stimulating acute phase protein synthesis, as well as the production of neutrophils in the bone marrow. It supports the growth of B cells and is antagonistic to regulatory T cells. - When psychologically stressed, the human body produces stress hormones like cortisol, which are able to trigger interleukin-6 release into the circulation. # Role as myokine IL-6 is also considered a myokine, a cytokine produced from muscle, which is elevated in response to muscle contraction. It is significantly elevated with exercise, and precedes the appearance of other cytokines in the circulation. During exercise, it is thought to act in a hormone-like manner to mobilize extracellular substrates and/or augment substrate delivery. IL-6 has extensive anti-inflammatory functions in its role as a myokine. IL-6 was the first myokine that was found to be secreted into the blood stream in response to muscle contractions. Aerobic exercise provokes a systemic cytokine response, including, for example, IL-6, IL-1 receptor antagonist (IL-1ra), and IL-10. IL-6 was serendipitously discovered as a myokine because of the observation that it increased in an exponential fashion proportional to the length of exercise and the amount of muscle mass engaged in the exercise. It has been consistently demonstrated that the plasma concentration of IL-6 increases during muscular exercise. This increase is followed by the appearance of IL-1ra and the anti-inflammatory cytokine IL-10. In general, the cytokine response to exercise and sepsis differs with regard to TNF-α. Thus, the cytokine response to exercise is not preceded by an increase in plasma-TNF-α. Following exercise, the basal plasma IL-6 concentration may increase up to 100-fold, but less dramatic increases are more frequent. The exercise-induced increase of plasma IL-6 occurs in an exponential manner and the peak IL-6 level is reached at the end of the exercise or shortly thereafter. It is the combination of mode, intensity, and duration of the exercise that determines the magnitude of the exercise-induced increase of plasma IL-6. IL-6 had previously been classified as a proinflammatory cytokine. Therefore, it was first thought that the exercise-induced IL-6 response was related to muscle damage. However, it has become evident that eccentric exercise is not associated with a larger increase in plasma IL-6 than exercise involving concentric "nondamaging" muscle contractions. This finding clearly demonstrates that muscle damage is not required to provoke an increase in plasma IL-6 during exercise. As a matter of fact, eccentric exercise may result in a delayed peak and a much slower decrease of plasma IL-6 during recovery. Recent work has shown that both upstream and downstream signalling pathways for IL-6 differ markedly between myocytes and macrophages. It appears that unlike IL-6 signalling in macrophages, which is dependent upon activation of the NFκB signalling pathway, intramuscular IL-6 expression is regulated by a network of signalling cascades, including the Ca2+/NFAT and glycogen/p38 MAPK pathways. Thus, when IL-6 is signalling in monocytes or macrophages, it creates a pro-inflammatory response, whereas IL-6 activation and signalling in muscle is totally independent of a preceding TNF-response or NFκB activation, and is anti-inflammatory. IL-6, among an increasing number of other recently identified myokines, thus remains an important topic in myokine research. It appears in muscle tissue and in the circulation during exercise at levels up to one hundred times basal rates, as noted, and is seen as having a beneficial impact on health and bodily functioning when elevated in response to physical exercise. IL-6 was the first myokine that was found to be secreted into the blood stream in response to muscle contractions. # Receptor IL-6 signals through a cell-surface type I cytokine receptor complex consisting of the ligand-binding IL-6Rα chain (CD126), and the signal-transducing component gp130 (also called CD130). CD130 is the common signal transducer for several cytokines including leukemia inhibitory factor (LIF), ciliary neurotropic factor, oncostatin M, IL-11 and cardiotrophin-1, and is almost ubiquitously expressed in most tissues. In contrast, the expression of CD126 is restricted to certain tissues. As IL-6 interacts with its receptor, it triggers the gp130 and IL-6R proteins to form a complex, thus activating the receptor. These complexes bring together the intracellular regions of gp130 to initiate a signal transduction cascade through certain transcription factors, Janus kinases (JAKs) and Signal Transducers and Activators of Transcription (STATs). IL-6 is probably the best-studied of the cytokines that use gp130, also known as IL-6 signal transducer (IL6ST), in their signalling complexes. Other cytokines that signal through receptors containing gp130 are Interleukin 11 (IL-11), Interleukin 27 (IL-27), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT-1), cardiotrophin-like cytokine (CLC), leukemia inhibitory factor (LIF), oncostatin M (OSM), Kaposi's sarcoma-associated herpesvirus interleukin 6-like protein (KSHV-IL6). These cytokines are commonly referred to as the IL-6 like or gp130 utilising cytokines In addition to the membrane-bound receptor, a soluble form of IL-6R (sIL-6R) has been purified from human serum and urine. Many neuronal cells are unresponsive to stimulation by IL-6 alone, but differentiation and survival of neuronal cells can be mediated through the action of sIL-6R. The sIL-6R/IL-6 complex can stimulate neurites outgrowth and promote survival of neurons and, hence, may be important in nerve regeneration through remyelination. # Interactions Interleukin-6 has been shown to interact with interleukin-6 receptor, and glycoprotein 130. There is considerable functional overlap and interaction between Substance P (SP), the natural ligand for the neurokinin type 1 receptor (NK1R, a mediator of immunomodulatory activity) and IL-6. # Role in disease IL-6 stimulates the inflammatory and auto-immune processes in many diseases such as diabetes, atherosclerosis, depression, Alzheimer's Disease, systemic lupus erythematosus, multiple myeloma, prostate cancer, Behçet's disease, and rheumatoid arthritis. Hence, there is an interest in developing anti-IL-6 agents as therapy against many of these diseases. The first such is tocilizumab, which has been approved for rheumatoid arthritis, Castleman's disease and systemic juvenile idiopathic arthritis. Others are in clinical trials. ## Rheumatoid arthritis The first FDA approved anti-IL-6 was for RA. ## Cancer Anti-IL-6 therapy was initially developed for treatment of autoimmune diseases, but due to the role of IL-6 in chronic inflammation, IL-6 blockade was also evaluated for cancer treatment. IL-6 was seen to have roles in tumor microenvironment regulation, production of breast cancer stem cell-like cells, metastasis through down-regulation of E-cadherin, and alteration of DNA methylation in oral cancer. Advanced/metastatic cancer patients have higher levels of IL-6 in their blood. One example of this is pancreatic cancer, with noted elevation of IL-6 present in patients correlating with poor survival rates. ## Infectious diseases ### Enterovirus 71 High IL-6 levels are associated with the development of encephalitis in children and immunodeficient mouse models infected with Enterovirus 71; this highly contagious virus normally causes a milder illness called Hand, foot, and mouth disease but can cause life-threatening encephalitis in some cases. EV71 patients with a certain gene polymorphism in IL-6 also appear to be more susceptible to developing encephalitis. ## Epigenetic modifications IL-6 has been shown to lead to several neurological diseases through its impact on epigenetic modification within the brain. IL-6 activates the Phosphoinositide 3-kinase (PI3K) pathway, and a downstream target of this pathway is the protein kinase B (PKB) (Hodge et al., 2007). IL-6 activated PKB can phosphorylate the nuclear localization signal on DNA methyltransferase-1 (DNMT1). This phosphorylation causes movement of DNMT1 to the nucleus, where it can be transcribed. DNMT1 recruits other DNMTs, including DNMT3A and DNMT3B, which, as a complex, recruit HDAC1. This complex adds methyl groups to CpG islands on gene promoters, repressing the chromatin structure surrounding the DNA sequence and inhibiting transcriptional machinery from accessing the gene to induce transcription. Increased IL-6, therefore, can hypermethylate DNA sequences and subsequently decrease gene expression through its effects on DNMT1 expression. ### Schizophrenia The induction of epigenetic modification by IL-6 has been proposed as a mechanism in the pathology of schizophrenia through the hypermethylation and repression of the GAD67 promoter. This hypermethylation may potentially lead to the decreased GAD67 levels seen in the brains of people with schizophrenia. GAD67 may be involved in the pathology of schizophrenia through its effect on GABA levels and on neural oscillations. Neural oscillations occur when inhibitory GABAergic neurons fire synchronously and cause inhibition of a multitude of target excitatory neurons at the same time, leading to a cycle of inhibition and disinhibition. These neural oscillations are impaired in schizophrenia, and these alterations may be responsible for both positive and negative symptoms of schizophrenia. ### Depression and major depressive disorder The epigenetic effects IL-6 have also been implicated in the pathology of depression. The effects of IL-6 on depression are mediated through the repression of brain-derived neurotrophic factor (BDNF) expression in the brain; DNMT1 hypermethylates the BDNF promoter and reduces BDNF levels. Altered BDNF function has been implicated in depression, which is likely due to epigenetic modification following IL-6 upregulation. BDNF is a neutrophic factor implicated in spine formation, density, and morphology on neurons. Downregulation of BDNF, therefore, may cause decreased connectivity in the brain. Depression is marked by altered connectivity, in particular between the anterior cingulate cortex and several other limbic areas, such as the hippocampus. The anterior cingulate cortex is responsible for detecting incongruences between expectation and perceived experience. Altered connectivity of the anterior cingulate cortex in depression, therefore, may cause altered emotions following certain experiences, leading to depressive reactions. This altered connectivity is mediated by IL-6 and its effect on epigenetic regulation of BDNF. Additional preclinical and clinical data, suggest that Substance P and IL-6 may act in concert to promote major depression. SP, a hybrid neurotransmitter-cytokine, is co-transmitted with BDNF through paleo-spinothalamic circuitry from the periphery with collaterals into key areas of the limbic system. However, both IL6 and SP mitigate expression of BDNF in brain regions associated with negative affect and memory. SP and IL6 both relax tight junctions of the blood brain barrier, such that effects seen in fMRI experiments with these molecules may be a bidirectional mix of neuronal, glial, capillary, synaptic, paracrine, or endocrine-like effects. At the cellular level, SP is noted to increase expression of interleukin-6 (IL-6) through PI-3K, p42/44 and p38 MAP kinase pathways. Data suggest that nuclear translocation of NF-κB regulates IL-6 overexpression in SP-stimulated cells. This is of key interest as: 1) a meta-analysis indicates an association of major depressive disorder, C-reactive protein and IL6 plasma concentrations, 2) NK1R antagonists studied by 3 independent groups in over 2000 patients from 1998-2013 validate the mechanism as dose-related, fully effective antidepressant, with a unique safety profile. (see Summary of NK1RAs in Major Depression), 3) the preliminary observation that plasma concentrations of IL6 are elevated in depressed patients with cancer, and 4) selective NK1RAs may eliminate endogenous SP stress-induced augmentation of IL-6 secretion pre-clinically. These and many other reports suggest that a clinical study of a neutralizing IL-6 biological or drug based antagonist is likely warranted in patients with major depressive disorder, with or without co-morbid chronic inflammatory based illnesses; that the combination of NK1RAs and IL6 blockers may represent a new, potentially biomarkable approach to major depression, and possibly bipolar disorder. The IL-6 antibody sirukumab is now undergoing clinical trials against major depressive disorder. ## Asthma Obesity is a known risk factor in the development of severe asthma. Recent data suggests that the inflammation associated with obesity, potentially mediated by the cytokine IL6, plays a role in causing poor lung function and increased risk for developing asthma exacerbations.	Interleukin 6 Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the IL6 gene.[1] In addition, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smooth muscle cells in the tunica media of many blood vessels also produce IL-6 as a pro-inflammatory cytokine. IL-6's role as an anti-inflammatory myokine is mediated through its inhibitory effects on TNF-alpha and IL-1, and activation of IL-1ra and IL-10. # Function - IL-6 is an important mediator of fever and of the acute phase response. - It is capable of crossing the blood-brain barrier[2] and initiating synthesis of PGE2 in the hypothalamus, thereby changing the body's temperature setpoint. - In muscle and fatty tissue, IL-6 stimulates energy mobilization that leads to increased body temperature. - IL-6 can be secreted by macrophages in response to specific microbial molecules, referred to as pathogen-associated molecular patterns (PAMPs). These PAMPs bind to an important group of detection molecules of the innate immune system, called pattern recognition receptors (PRRs), including Toll-like receptors (TLRs). These are present on the cell surface and intracellular compartments and induce intracellular signaling cascades that give rise to inflammatory cytokine production. - IL-6 is found in many supplemental cloning media such as briclone. - Inhibitors of IL-6 (including estrogen) are used to treat postmenopausal osteoporosis. - IL-6 is also produced by adipocytes and is thought to be a reason why obese individuals have higher endogeneous levels of CRP.[3] - Intranasally administered IL-6 has been shown to improve sleep-associated consolidation of emotional memories.[4] - IL-6 is responsible for stimulating acute phase protein synthesis, as well as the production of neutrophils in the bone marrow. It supports the growth of B cells and is antagonistic to regulatory T cells. - When psychologically stressed, the human body produces stress hormones like cortisol, which are able to trigger interleukin-6 release into the circulation.[5] # Role as myokine IL-6 is also considered a myokine, a cytokine produced from muscle, which is elevated in response to muscle contraction.[6] It is significantly elevated with exercise, and precedes the appearance of other cytokines in the circulation. During exercise, it is thought to act in a hormone-like manner to mobilize extracellular substrates and/or augment substrate delivery.[7] IL-6 has extensive anti-inflammatory functions in its role as a myokine. IL-6 was the first myokine that was found to be secreted into the blood stream in response to muscle contractions.[8] Aerobic exercise provokes a systemic cytokine response, including, for example, IL-6, IL-1 receptor antagonist (IL-1ra), and IL-10. IL-6 was serendipitously discovered as a myokine because of the observation that it increased in an exponential fashion proportional to the length of exercise and the amount of muscle mass engaged in the exercise. It has been consistently demonstrated that the plasma concentration of IL-6 increases during muscular exercise. This increase is followed by the appearance of IL-1ra and the anti-inflammatory cytokine IL-10. In general, the cytokine response to exercise and sepsis differs with regard to TNF-α. Thus, the cytokine response to exercise is not preceded by an increase in plasma-TNF-α. Following exercise, the basal plasma IL-6 concentration may increase up to 100-fold, but less dramatic increases are more frequent. The exercise-induced increase of plasma IL-6 occurs in an exponential manner and the peak IL-6 level is reached at the end of the exercise or shortly thereafter. It is the combination of mode, intensity, and duration of the exercise that determines the magnitude of the exercise-induced increase of plasma IL-6.[9] IL-6 had previously been classified as a proinflammatory cytokine. Therefore, it was first thought that the exercise-induced IL-6 response was related to muscle damage.[10] However, it has become evident that eccentric exercise is not associated with a larger increase in plasma IL-6 than exercise involving concentric "nondamaging" muscle contractions. This finding clearly demonstrates that muscle damage is not required to provoke an increase in plasma IL-6 during exercise. As a matter of fact, eccentric exercise may result in a delayed peak and a much slower decrease of plasma IL-6 during recovery.[11] Recent work has shown that both upstream and downstream signalling pathways for IL-6 differ markedly between myocytes and macrophages. It appears that unlike IL-6 signalling in macrophages, which is dependent upon activation of the NFκB signalling pathway, intramuscular IL-6 expression is regulated by a network of signalling cascades, including the Ca2+/NFAT and glycogen/p38 MAPK pathways. Thus, when IL-6 is signalling in monocytes or macrophages, it creates a pro-inflammatory response, whereas IL-6 activation and signalling in muscle is totally independent of a preceding TNF-response or NFκB activation, and is anti-inflammatory.[12] IL-6, among an increasing number of other recently identified myokines, thus remains an important topic in myokine research. It appears in muscle tissue and in the circulation during exercise at levels up to one hundred times basal rates, as noted, and is seen as having a beneficial impact on health and bodily functioning when elevated in response to physical exercise.[13] IL-6 was the first myokine that was found to be secreted into the blood stream in response to muscle contractions.[14] # Receptor IL-6 signals through a cell-surface type I cytokine receptor complex consisting of the ligand-binding IL-6Rα chain (CD126), and the signal-transducing component gp130 (also called CD130). CD130 is the common signal transducer for several cytokines including leukemia inhibitory factor (LIF), ciliary neurotropic factor, oncostatin M, IL-11 and cardiotrophin-1, and is almost ubiquitously expressed in most tissues. In contrast, the expression of CD126 is restricted to certain tissues. As IL-6 interacts with its receptor, it triggers the gp130 and IL-6R proteins to form a complex, thus activating the receptor. These complexes bring together the intracellular regions of gp130 to initiate a signal transduction cascade through certain transcription factors, Janus kinases (JAKs) and Signal Transducers and Activators of Transcription (STATs).[15] IL-6 is probably the best-studied of the cytokines that use gp130, also known as IL-6 signal transducer (IL6ST), in their signalling complexes. Other cytokines that signal through receptors containing gp130 are Interleukin 11 (IL-11), Interleukin 27 (IL-27), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT-1), cardiotrophin-like cytokine (CLC), leukemia inhibitory factor (LIF), oncostatin M (OSM), Kaposi's sarcoma-associated herpesvirus interleukin 6-like protein (KSHV-IL6).[16] These cytokines are commonly referred to as the IL-6 like or gp130 utilising cytokines [17] In addition to the membrane-bound receptor, a soluble form of IL-6R (sIL-6R) has been purified from human serum and urine. Many neuronal cells are unresponsive to stimulation by IL-6 alone, but differentiation and survival of neuronal cells can be mediated through the action of sIL-6R. The sIL-6R/IL-6 complex can stimulate neurites outgrowth and promote survival of neurons and, hence, may be important in nerve regeneration through remyelination. # Interactions Interleukin-6 has been shown to interact with interleukin-6 receptor,[18][19][20] and glycoprotein 130.[21] There is considerable functional overlap and interaction between Substance P (SP), the natural ligand for the neurokinin type 1 receptor (NK1R, a mediator of immunomodulatory activity) and IL-6. # Role in disease IL-6 stimulates the inflammatory and auto-immune processes in many diseases such as diabetes,[22] atherosclerosis,[23] depression,[24] Alzheimer's Disease,[25] systemic lupus erythematosus,[26] multiple myeloma,[27] prostate cancer,[28] Behçet's disease,[29] and rheumatoid arthritis.[30] Hence, there is an interest in developing anti-IL-6 agents as therapy against many of these diseases.[31][32] The first such is tocilizumab, which has been approved for rheumatoid arthritis,[33] Castleman's disease[34] and systemic juvenile idiopathic arthritis.[35] Others are in clinical trials.[36] ## Rheumatoid arthritis The first FDA approved anti-IL-6 was for RA. ## Cancer Anti-IL-6 therapy was initially developed for treatment of autoimmune diseases, but due to the role of IL-6 in chronic inflammation, IL-6 blockade was also evaluated for cancer treatment.[37][38] IL-6 was seen to have roles in tumor microenvironment regulation,[39] production of breast cancer stem cell-like cells,[40] metastasis through down-regulation of E-cadherin,[41] and alteration of DNA methylation in oral cancer.[42] Advanced/metastatic cancer patients have higher levels of IL-6 in their blood.[43] One example of this is pancreatic cancer, with noted elevation of IL-6 present in patients correlating with poor survival rates.[44] ## Infectious diseases ### Enterovirus 71 High IL-6 levels are associated with the development of encephalitis in children and immunodeficient mouse models infected with Enterovirus 71; this highly contagious virus normally causes a milder illness called Hand, foot, and mouth disease but can cause life-threatening encephalitis in some cases. EV71 patients with a certain gene polymorphism in IL-6 also appear to be more susceptible to developing encephalitis. ## Epigenetic modifications IL-6 has been shown to lead to several neurological diseases through its impact on epigenetic modification within the brain.[45][46] IL-6 activates the Phosphoinositide 3-kinase (PI3K) pathway, and a downstream target of this pathway is the protein kinase B (PKB) (Hodge et al., 2007). IL-6 activated PKB can phosphorylate the nuclear localization signal on DNA methyltransferase-1 (DNMT1).[47] This phosphorylation causes movement of DNMT1 to the nucleus, where it can be transcribed.[47] DNMT1 recruits other DNMTs, including DNMT3A and DNMT3B, which, as a complex, recruit HDAC1.[46] This complex adds methyl groups to CpG islands on gene promoters, repressing the chromatin structure surrounding the DNA sequence and inhibiting transcriptional machinery from accessing the gene to induce transcription.[46] Increased IL-6, therefore, can hypermethylate DNA sequences and subsequently decrease gene expression through its effects on DNMT1 expression.[48] ### Schizophrenia The induction of epigenetic modification by IL-6 has been proposed as a mechanism in the pathology of schizophrenia through the hypermethylation and repression of the GAD67 promoter.[46] This hypermethylation may potentially lead to the decreased GAD67 levels seen in the brains of people with schizophrenia.[49] GAD67 may be involved in the pathology of schizophrenia through its effect on GABA levels and on neural oscillations.[50] Neural oscillations occur when inhibitory GABAergic neurons fire synchronously and cause inhibition of a multitude of target excitatory neurons at the same time, leading to a cycle of inhibition and disinhibition.[50] These neural oscillations are impaired in schizophrenia, and these alterations may be responsible for both positive and negative symptoms of schizophrenia.[51] ### Depression and major depressive disorder The epigenetic effects IL-6 have also been implicated in the pathology of depression. The effects of IL-6 on depression are mediated through the repression of brain-derived neurotrophic factor (BDNF) expression in the brain; DNMT1 hypermethylates the BDNF promoter and reduces BDNF levels.[52] Altered BDNF function has been implicated in depression,[53] which is likely due to epigenetic modification following IL-6 upregulation.[52] BDNF is a neutrophic factor implicated in spine formation, density, and morphology on neurons.[54] Downregulation of BDNF, therefore, may cause decreased connectivity in the brain. Depression is marked by altered connectivity, in particular between the anterior cingulate cortex and several other limbic areas, such as the hippocampus.[55] The anterior cingulate cortex is responsible for detecting incongruences between expectation and perceived experience.[56] Altered connectivity of the anterior cingulate cortex in depression, therefore, may cause altered emotions following certain experiences, leading to depressive reactions.[56] This altered connectivity is mediated by IL-6 and its effect on epigenetic regulation of BDNF.[52] Additional preclinical and clinical data, suggest that Substance P [SP] and IL-6 may act in concert to promote major depression. SP, a hybrid neurotransmitter-cytokine, is co-transmitted with BDNF through paleo-spinothalamic circuitry from the periphery with collaterals into key areas of the limbic system. However, both IL6 and SP mitigate expression of BDNF in brain regions associated with negative affect and memory. SP and IL6 both relax tight junctions of the blood brain barrier, such that effects seen in fMRI experiments with these molecules may be a bidirectional mix of neuronal, glial, capillary, synaptic, paracrine, or endocrine-like effects. At the cellular level, SP is noted to increase expression of interleukin-6 (IL-6) through PI-3K, p42/44 and p38 MAP kinase pathways. Data suggest that nuclear translocation of NF-κB regulates IL-6 overexpression in SP-stimulated cells.[57] This is of key interest as: 1) a meta-analysis indicates an association of major depressive disorder, C-reactive protein and IL6 plasma concentrations,[58] 2) NK1R antagonists [five molecules] studied by 3 independent groups in over 2000 patients from 1998-2013 validate the mechanism as dose-related, fully effective antidepressant, with a unique safety profile.[59][60] (see Summary of NK1RAs in Major Depression), 3) the preliminary observation that plasma concentrations of IL6 are elevated in depressed patients with cancer,[61] and 4) selective NK1RAs may eliminate endogenous SP stress-induced augmentation of IL-6 secretion pre-clinically.[62] These and many other reports suggest that a clinical study of a neutralizing IL-6 biological or drug based antagonist is likely warranted in patients with major depressive disorder, with or without co-morbid chronic inflammatory based illnesses; that the combination of NK1RAs and IL6 blockers may represent a new, potentially biomarkable approach to major depression, and possibly bipolar disorder. The IL-6 antibody sirukumab is now undergoing clinical trials against major depressive disorder.[63] ## Asthma Obesity is a known risk factor in the development of severe asthma. Recent data suggests that the inflammation associated with obesity, potentially mediated by the cytokine IL6, plays a role in causing poor lung function and increased risk for developing asthma exacerbations.[64]	https://www.wikidoc.org/index.php/IL-6
684bfa733ca59764bb08ab2425e9d1e1bd504074	wikidoc	Interleukin 7	Interleukin 7 Interleukin 7 (IL-7) is a protein that in humans is encoded by the IL7 gene. IL-7 is a hematopoietic growth factor secreted by stromal cells in the bone marrow and thymus. It is also produced by keratinocytes, dendritic cells, hepatocytes, neurons, and epithelial cells, but is not produced by normal lymphocytes. # Structure The three-dimensional structure of IL-7 in complex with the ectodomain of IL7R has been determined using X-ray diffraction. # Function ## Lymphocyte maturation IL-7 stimulates the differentiation of multipotent (pluripotent) hematopoietic stem cells into lymphoid progenitor cells (as opposed to myeloid progenitor cells where differentiation is stimulated by IL-3). It also stimulates proliferation of all cells in the lymphoid lineage (B cells, T cells and NK cells). It is important for proliferation during certain stages of B-cell maturation, T and NK cell survival, development and homeostasis. IL-7 is a cytokine important for B and T cell development. This cytokine and the hepatocyte growth factor (HGF) form a heterodimer that functions as a pre-pro-B cell growth-stimulating factor. This cytokine is found to be a cofactor for V(D)J rearrangement of the T cell receptor beta (TCRß) during early T cell development. This cytokine can be produced locally by intestinal epithelial and epithelial goblet cells, and may serve as a regulatory factor for intestinal mucosal lymphocytes. Knockout studies in mice suggested that this cytokine plays an essential role in lymphoid cell survival. ## IL-7 signaling IL-7 binds to the IL-7 receptor, a heterodimer consisting of Interleukin-7 receptor alpha and common gamma chain receptor. Binding results in a cascade of signals important for T-cell development within the thymus and survival within the periphery. Knockout mice which genetically lack IL-7 receptor exhibit thymic atrophy, arrest of T-cell development at the double positive stage, and severe lymphopenia. Administration of IL-7 to mice results in an increase in recent thymic emigrants, increases in B and T cells, and increased recovery of T cells after cyclophosphamide administration or after bone marrow transplantation. # Disease ## Cancer IL-7 promotes hematological malignancies (acute lymphoblastic leukemia, T cell lymphoma). ## Viral Infections Elevated levels of IL-7 have also been detected in the plasma of HIV-infected patients. # Clinical application IL-7 as an immunotherapy agent has been examined in many pre-clinical animal studies and more recently in human clinical trials for various malignancies and during HIV infection. ## Cancer Recombinant IL-7 has been safely administered to patients in several phase I and II clinical trials. A human study of IL-7 in patients with cancer demonstrated that administration of this cytokine can transiently disrupt the homeostasis of both CD8+ and CD4+ T cells with a commensurate decrease in the percentage of CD4+CD25+Foxp3+ T regulatory cells. No objective cancer regression was observed, however a dose limiting toxicity (DLT) was not reached in this study due to the development of neutralizing antibodies against the recombinant cytokine. ## HIV infection Associated with antiretroviral therapy, IL-7 administration decreased local and systemic inflammations in patients that had incomplete T-cell reconstitution. These results suggest that IL-7 therapy can possibly improve the quality of life of those patients. ## Transplantation IL-7 could also be beneficial in improving immune recovery after allogenic stem cell transplant.	Interleukin 7 Interleukin 7 (IL-7) is a protein[1] that in humans is encoded by the IL7 gene.[2][3][4] IL-7 is a hematopoietic growth factor secreted by stromal cells in the bone marrow and thymus. It is also produced by keratinocytes,[5] dendritic cells,[6] hepatocytes,[7] neurons, and epithelial cells,[8] but is not produced by normal lymphocytes.[9] # Structure The three-dimensional structure of IL-7 in complex with the ectodomain of IL7R has been determined using X-ray diffraction.[10] # Function ## Lymphocyte maturation IL-7 stimulates the differentiation of multipotent (pluripotent) hematopoietic stem cells into lymphoid progenitor cells (as opposed to myeloid progenitor cells where differentiation is stimulated by IL-3).[citation needed] It also stimulates proliferation of all cells in the lymphoid lineage (B cells, T cells and NK cells).[citation needed] It is important for proliferation during certain stages of B-cell maturation, T and NK cell survival, development and homeostasis.[citation needed] IL-7 is a cytokine important for B and T cell development. This cytokine and the hepatocyte growth factor (HGF) form a heterodimer that functions as a pre-pro-B cell growth-stimulating factor. This cytokine is found to be a cofactor for V(D)J rearrangement of the T cell receptor beta (TCRß) during early T cell development.[11] This cytokine can be produced locally by intestinal epithelial and epithelial goblet cells, and may serve as a regulatory factor for intestinal mucosal lymphocytes.[citation needed] Knockout studies in mice suggested that this cytokine plays an essential role in lymphoid cell survival.[12] ## IL-7 signaling IL-7 binds to the IL-7 receptor, a heterodimer consisting of Interleukin-7 receptor alpha and common gamma chain receptor.[13] Binding results in a cascade of signals important for T-cell development within the thymus and survival within the periphery. Knockout mice which genetically lack IL-7 receptor exhibit thymic atrophy, arrest of T-cell development at the double positive stage, and severe lymphopenia. Administration of IL-7 to mice results in an increase in recent thymic emigrants, increases in B and T cells, and increased recovery of T cells after cyclophosphamide administration or after bone marrow transplantation. # Disease ## Cancer IL-7 promotes hematological malignancies (acute lymphoblastic leukemia, T cell lymphoma).[14] ## Viral Infections Elevated levels of IL-7 have also been detected in the plasma of HIV-infected patients.[15] # Clinical application IL-7 as an immunotherapy agent has been examined in many pre-clinical animal studies and more recently in human clinical trials for various malignancies and during HIV infection.[9][16] ## Cancer Recombinant IL-7 has been safely administered to patients in several phase I and II clinical trials. A human study of IL-7 in patients with cancer demonstrated that administration of this cytokine can transiently disrupt the homeostasis of both CD8+ and CD4+ T cells with a commensurate decrease in the percentage of CD4+CD25+Foxp3+ T regulatory cells.[17] No objective cancer regression was observed, however a dose limiting toxicity (DLT) was not reached in this study due to the development of neutralizing antibodies against the recombinant cytokine. ## HIV infection Associated with antiretroviral therapy, IL-7 administration decreased local and systemic inflammations in patients that had incomplete T-cell reconstitution. These results suggest that IL-7 therapy can possibly improve the quality of life of those patients.[18] ## Transplantation IL-7 could also be beneficial in improving immune recovery after allogenic stem cell transplant.[19]	https://www.wikidoc.org/index.php/IL-7
0914fffefc019646c6691678252e95c4c7cecf8a	wikidoc	Interleukin 8	Interleukin 8 Interleukin 8 (IL8 or chemokine (C-X-C motif) ligand 8, CXCL8) is a chemokine produced by macrophages and other cell types such as epithelial cells, airway smooth muscle cells and endothelial cells. Endothelial cells store IL-8 in their storage vesicles, the Weibel-Palade bodies. In humans, the interleukin-8 protein is encoded by the CXCL8 gene. IL-8 is initially produced as a precursor peptide of 99 amino acids which then undergoes cleavage to create several active IL-8 isoforms. In culture, a 72 amino acid peptide is the major form secreted by macrophages. There are many receptors on the surface membrane capable of binding IL-8; the most frequently studied types are the G protein-coupled serpentine receptors CXCR1 and CXCR2. Expression and affinity for IL-8 differs between the two receptors (CXCR1 > CXCR2). Through a chain of biochemical reactions, IL-8 is secreted and is an important mediator of the immune reaction in the innate immune system response. # Function IL-8, also known as neutrophil chemotactic factor, has two primary functions. It induces chemotaxis in target cells, primarily neutrophils but also other granulocytes, causing them to migrate toward the site of infection. IL-8 also stimulates phagocytosis once they have arrived. IL-8 is also known to be a potent promoter of angiogenesis. In target cells, IL-8 induces a series of physiological responses required for migration and phagocytosis, such as increases in intracellular Ca2+, exocytosis (e.g. histamine release), and the respiratory burst. IL-8 can be secreted by any cells with toll-like receptors that are involved in the innate immune response. Usually, it is the macrophages that see an antigen first, and thus are the first cells to release IL-8 to recruit other cells. Both monomer and homodimer forms of IL-8 have been reported to be potent inducers of the chemokine receptors CXCR1 and CXCR2. The homodimer is more potent, but methylation of Leu25 can block the activity of homodimers. IL-8 is believed to play a role in the pathogenesis of bronchiolitis, a common respiratory tract disease caused by viral infection. IL-8 is a member of the CXC chemokine family. The genes encoding this and the other ten members of the CXC chemokine family form a cluster in a region mapped to chromosome 4q. # CXCL-8 mediated chemotaxis of the neutrophil CXCL8 is the primary cytokine involved in the recruitment of neutrophils to the site of damage or infection; in a process called chemotaxis. A number of variables are essential for the successful chemotaxis of neutrophils, including the increased expression of high affinity adhesion molecules to secure the neutrophil to the endothelium near the affected site (and is therefore not washed away into the circulatory system), and that the neutrophil can digest its way through the basement membrane and the extracellular matrix (ECM) to reach affected site. CXCL8 plays a key role in inducing the cell signalling necessary to bring about these changes. Firstly, at the site of infection histamine release causes vasodilation of the capillaries near the injured area which slows down the blood flow in the region and encourages leukocytes, such as neutrophils, to come closer to the endothelium, and away from the centre of the lumen where the rate of blood flow is highest. Once this occurs weak interactions are made between the selectins expressed on the neutrophil and endothelial cells (expression of which is also increased through the action of CXCL8 and other cytokines). On the neutrophil these are: L selectins, and on the endothelial cell: P and E selectins. This causes the "rolling" phase of chemotaxis. Once the neutrophil is rolling along the endothelium, it will come into contact with a CXCL8 molecule expressed on the surface which stimulates the cell signalling pathway, mediated through a G-coupled-protein-receptor. The binding of CXCL8 to CXCR1/2 on the neutrophil stimulates the neutrophils to upregulate their expression of the integrin, LFA-1, which takes part in high affinity bonding with ICAM-1 receptors expressed on the endothelium. The expression and affinity of LFA-1 is significantly increased to maximise binding. This causes the neutrophil to slow down more until it is stationary. Another key function of the cell signalling stimulated by CXCL8, is the initiation of the oxidative burst. This process allows the build up of proteolytic enzymes and reactive oxygen species (ROS) which are necessary to break down the ECM and basement membrane. These are released in secretory granules, along with more integrins. The release of ROS and damaging enzymes is regulated to minimise host damage, but continues to reach site of infection at which it will carry out its effector functions. # Target cells While neutrophil granulocytes are the primary target cells of IL-8, there are a relatively wide range of cells (endothelial cells, macrophages, mast cells, and keratinocytes) that respond to this chemokine. The chemoattractant activity of IL-8 in similar concentrations to vertebrates was proven in Tetrahymena pyriformis, which suggests a phylogenetically well-conserved structure and function for this chemokine. # Clinical significance Interleukin-8 is a key mediator associated with inflammation where it plays a key role in neutrophil recruitment and neutrophil degranulation. As an example, it has been cited as a proinflammatory mediator in gingivitis and psoriasis. Interleukin-8 secretion is increased by oxidant stress, which thereby cause the recruitment of inflammatory cells and induces a further increase in oxidant stress mediators, making it a key parameter in localized inflammation. IL-8 was shown to be associated with obesity. IL-8 has also been implied to have a role in colorectal cancer by acting as an autocrine growth factor for colon carcinoma cell lines or the promotion of division and possible migration by cleaving metalloproteinase molecules. If a pregnant mother has high levels of interleukin-8, there is an increased risk of schizophrenia in her offspring. High levels of Interleukin 8 have been shown to reduce the likelihood of positive responses to antipsychotic medication in schizophrenia. IL-8 has also been implicated in the pathology of cystic fibrosis. Through its action as a signalling molecule IL-8 is capable of recruiting and guiding neutrophils to the lung epithelium. Overstimulation and dysfunction of these recruited neutrophils within the airways results in release of a number of pro-inflammatory molecules and proteases resulting in further damage of lung tissue. # Nomenclature IL-8 was renamed CXCL8 by the Chemokine Nomenclature Subcommittee of the International Union of Immunological Societies,. Its approved HUGO gene symbol is CXCL8. # Regulation of expression The expression of IL-8 is negatively regulated by a number of mechanisms. MiRNA-146a/b-5p indirectly represses IL-8 expression by silencing the expression of IRAK1. Additionally, the 3'UTR of IL-8 contains a A/U-rich element that makes it extremely unstable under certain conditions. IL-8 expression is also regulated by the transcription factor NF-κB. NF-κB regulation represents a novel anti-IL-8 therapy for use in inflammatory diseases such as cystic fibrosis.	Interleukin 8 Interleukin 8 (IL8 or chemokine (C-X-C motif) ligand 8, CXCL8) is a chemokine produced by macrophages and other cell types such as epithelial cells, airway smooth muscle cells[1] and endothelial cells. Endothelial cells store IL-8 in their storage vesicles, the Weibel-Palade bodies.[2][3] In humans, the interleukin-8 protein is encoded by the CXCL8 gene.[4] IL-8 is initially produced as a precursor peptide of 99 amino acids which then undergoes cleavage to create several active IL-8 isoforms.[5] In culture, a 72 amino acid peptide is the major form secreted by macrophages.[5] There are many receptors on the surface membrane capable of binding IL-8; the most frequently studied types are the G protein-coupled serpentine receptors CXCR1 and CXCR2. Expression and affinity for IL-8 differs between the two receptors (CXCR1 > CXCR2). Through a chain of biochemical reactions, IL-8 is secreted and is an important mediator of the immune reaction in the innate immune system response. # Function IL-8, also known as neutrophil chemotactic factor, has two primary functions. It induces chemotaxis in target cells, primarily neutrophils but also other granulocytes, causing them to migrate toward the site of infection. IL-8 also stimulates phagocytosis once they have arrived. IL-8 is also known to be a potent promoter of angiogenesis. In target cells, IL-8 induces a series of physiological responses required for migration and phagocytosis, such as increases in intracellular Ca2+, exocytosis (e.g. histamine release), and the respiratory burst. IL-8 can be secreted by any cells with toll-like receptors that are involved in the innate immune response. Usually, it is the macrophages that see an antigen first, and thus are the first cells to release IL-8 to recruit other cells. Both monomer and homodimer forms of IL-8 have been reported to be potent inducers of the chemokine receptors CXCR1 and CXCR2. The homodimer is more potent, but methylation of Leu25 can block the activity of homodimers. IL-8 is believed to play a role in the pathogenesis of bronchiolitis, a common respiratory tract disease caused by viral infection.[citation needed] IL-8 is a member of the CXC chemokine family. The genes encoding this and the other ten members of the CXC chemokine family form a cluster in a region mapped to chromosome 4q.[4][6] # CXCL-8 mediated chemotaxis of the neutrophil CXCL8 is the primary cytokine involved in the recruitment of neutrophils to the site of damage or infection; in a process called chemotaxis. A number of variables are essential for the successful chemotaxis of neutrophils, including the increased expression of high affinity adhesion molecules to secure the neutrophil to the endothelium near the affected site (and is therefore not washed away into the circulatory system), and that the neutrophil can digest its way through the basement membrane and the extracellular matrix (ECM) to reach affected site. CXCL8 plays a key role in inducing the cell signalling necessary to bring about these changes.[7] Firstly, at the site of infection histamine release causes vasodilation of the capillaries near the injured area which slows down the blood flow in the region and encourages leukocytes, such as neutrophils, to come closer to the endothelium, and away from the centre of the lumen where the rate of blood flow is highest. Once this occurs weak interactions are made between the selectins expressed on the neutrophil and endothelial cells (expression of which is also increased through the action of CXCL8 and other cytokines). On the neutrophil these are: L selectins, and on the endothelial cell: P and E selectins. This causes the "rolling" phase of chemotaxis. Once the neutrophil is rolling along the endothelium, it will come into contact with a CXCL8 molecule expressed on the surface which stimulates the cell signalling pathway, mediated through a G-coupled-protein-receptor. The binding of CXCL8 to CXCR1/2 on the neutrophil stimulates the neutrophils to upregulate their expression of the integrin, LFA-1, which takes part in high affinity bonding with ICAM-1 receptors expressed on the endothelium. The expression and affinity of LFA-1 is significantly increased to maximise binding. This causes the neutrophil to slow down more until it is stationary. Another key function of the cell signalling stimulated by CXCL8, is the initiation of the oxidative burst. This process allows the build up of proteolytic enzymes and reactive oxygen species (ROS) which are necessary to break down the ECM and basement membrane. These are released in secretory granules, along with more integrins. The release of ROS and damaging enzymes is regulated to minimise host damage, but continues to reach site of infection at which it will carry out its effector functions.[7] # Target cells While neutrophil granulocytes are the primary target cells of IL-8, there are a relatively wide range of cells (endothelial cells, macrophages, mast cells, and keratinocytes) that respond to this chemokine. The chemoattractant activity of IL-8 in similar concentrations to vertebrates was proven in Tetrahymena pyriformis, which suggests a phylogenetically well-conserved structure and function for this chemokine.[8] # Clinical significance Interleukin-8 is a key mediator associated with inflammation where it plays a key role in neutrophil recruitment and neutrophil degranulation.[9] As an example, it has been cited as a proinflammatory mediator in gingivitis[10] and psoriasis. Interleukin-8 secretion is increased by oxidant stress, which thereby cause the recruitment of inflammatory cells and induces a further increase in oxidant stress mediators, making it a key parameter in localized inflammation.[11] IL-8 was shown to be associated with obesity.[12] IL-8 has also been implied to have a role in colorectal cancer by acting as an autocrine growth factor for colon carcinoma cell lines[13] or the promotion of division and possible migration by cleaving metalloproteinase molecules.[14] If a pregnant mother has high levels of interleukin-8, there is an increased risk of schizophrenia in her offspring.[15] High levels of Interleukin 8 have been shown to reduce the likelihood of positive responses to antipsychotic medication in schizophrenia.[16] IL-8 has also been implicated in the pathology of cystic fibrosis. Through its action as a signalling molecule IL-8 is capable of recruiting and guiding neutrophils to the lung epithelium. Overstimulation and dysfunction of these recruited neutrophils within the airways results in release of a number of pro-inflammatory molecules and proteases resulting in further damage of lung tissue.[17] # Nomenclature IL-8 was renamed CXCL8 by the Chemokine Nomenclature Subcommittee of the International Union of Immunological Societies,.[18] Its approved HUGO gene symbol is CXCL8. # Regulation of expression The expression of IL-8 is negatively regulated by a number of mechanisms. MiRNA-146a/b-5p indirectly represses IL-8 expression by silencing the expression of IRAK1.[19] Additionally, the 3'UTR of IL-8 contains a A/U-rich element that makes it extremely unstable under certain conditions. IL-8 expression is also regulated by the transcription factor NF-κB.[20] NF-κB regulation represents a novel anti-IL-8 therapy for use in inflammatory diseases such as cystic fibrosis.	https://www.wikidoc.org/index.php/IL-8
79eaf9af0100b42f4d26e27c60d0f4155263d7f7	wikidoc	Interleukin 9	Interleukin 9 Interleukin 9, also known as IL-9, is a pleiotropic cytokine (cell signalling molecule) belonging to the group of interleukins. IL-9 is produced by variety of cells like mast cells, NKT cells, Th2, Th17, Treg, ILC2, and Th9 cells in different amounts. Among them, Th9 cells are regarded as the major CD4+ T cells that produce IL-9. # Functions Il-9 is a cytokine secreted by CD4+ helper cells that acts as a regulator of a variety of hematopoietic cells. This cytokine stimulates cell proliferation and prevents apoptosis. It functions through the interleukin-9 receptor (IL9R), which activates different signal transducer and activator (STAT) proteins namely STAT1, STAT3 and STAT5 and thus connects this cytokine to various biological processes. The gene encoding this cytokine has been identified as a candidate gene for asthma. Genetic studies on a mouse model of asthma demonstrated that this cytokine is a determining factor in the pathogenesis of bronchial hyperresponsiveness. Interleukin-9 has also shown to inhibit melanoma growth in mice. Additionally, it gives rise to the multiplication of hematologic neoplasias and also Hodgkin's lymphoma in humans but IL-9 also has antitumor properties in solid tumors,for example melanoma. # Discovery IL-9 was first described in the late 1980s as a member of a growing number of cytokines that had pleiotropic functions in the immune system.IL-9 remains an understudied cytokine even though it has been allocated with many biological functions.It was first purified and characterized as a T cell and mast cell growth factor and termed as P40, based on their molecular weight, or Mast cell growth-enhancing activity (MEA).The cloning and complete amino acid sequencing of P40 disclosed that it is structurally different from other T cells growth factors. So, it was named IL-9 based on its biological effects on both myeloid and lymphoid cells. The identification and cloning was first done by Yang and colleagues as a mitogenic factor for a human megakaryoblastic leukemia.The same human cDNA was isolated again by cross-hybridization with the mouse IL-9 probe. # Gene location The human IL-9 gene is located on the long arm of human chromosome 5 at band 5q31-32, a region which is not found in a number of patients with acquired chromosome 5q deletion syndrome. # Protein structure IL-9 protein sequence contains 144 residues with a typical signal peptide of 18 amino acids.There is also the presence of 10 cysteines of the maturepolypeptide. 4 potential N-linked glycosylation sites are observed too. The genomic structure of IL-9 consists of 10 exons. Among them, exons 3 and 7 encodes the extracellular domain, exon 8 encodes the transmembrane domain, and exons 9 and 10 encodes the cytoplasmic domain. Both the human and murine IL-9 receptors contains very high percentage of serine and proline in their cytoplasmic domain. # Production Interleukin 33 (IL-33) induces IL-9 expression and secretion in T cells, which was confirmed by the results obtained in mice by using Human in vitro system. Whereas the report of others confirms that TGF-β is an essential factor for IL-9 induction. For the first time (Lars Blom,Britta C. Poulsen,Bettina M. Jensen,Anker Hansen and Lars K. Poulsen published a journal online in 2011 Jul 6),indicating that TGF-β may be important for production of IL-9 but it is not only the definite requirement for IL-9 induction, since cultures with IL-33 without TGF-β have noticeably increased secretion of IL-9, suggesting an important role of IL-33, even though that the effect was not found significant on the gene level. # IL-9 expression The analysis of IL-9 expression in different types of tumours such as Large cell anaplastic lymphoma (LCAL) and Hodgkin's Disease (HD) by Northern blot analysis and in situ hybridization has showed that IL-9 is not involved as an autocrine growth factor in the pathogenesis of most B and T-cell lymphomas, but it may have a part in HD and LCAL autocrine growth. The further investigation could be done to conclude another probability, that, the in vivo overexpression of IL-9 might show the unique symptoms related to eosinophilia which was recently reported for Interleukin 5 positive cases of HD. IL-9 was found to be the first physiological stimulus triggering BCL3 expression in T cells and mast cells by the analysis done in mouse.	Interleukin 9 Interleukin 9, also known as IL-9, is a pleiotropic cytokine (cell signalling molecule) belonging to the group of interleukins.[1] IL-9 is produced by variety of cells like mast cells, NKT cells, Th2, Th17, Treg, ILC2, and Th9 cells in different amounts. Among them, Th9 cells are regarded as the major CD4+ T cells that produce IL-9.[2] # Functions Il-9 is a cytokine secreted by CD4+ helper cells that acts as a regulator of a variety of hematopoietic cells.[3] This cytokine stimulates cell proliferation and prevents apoptosis. It functions through the interleukin-9 receptor (IL9R), which activates different signal transducer and activator (STAT) proteins namely STAT1, STAT3 and STAT5 and thus connects this cytokine to various biological processes. The gene encoding this cytokine has been identified as a candidate gene for asthma. Genetic studies on a mouse model of asthma demonstrated that this cytokine is a determining factor in the pathogenesis of bronchial hyperresponsiveness.[1] Interleukin-9 has also shown to inhibit melanoma growth in mice.[4] Additionally, it gives rise to the multiplication of hematologic neoplasias and also Hodgkin's lymphoma in humans but IL-9 also has antitumor properties in solid tumors,for example melanoma.[2] # Discovery IL-9 was first described in the late 1980s as a member of a growing number of cytokines that had pleiotropic functions in the immune system.IL-9 remains an understudied cytokine even though it has been allocated with many biological functions.It was first purified and characterized as a T cell and mast cell growth factor and termed as P40, based on their molecular weight, or Mast cell growth-enhancing activity (MEA).The cloning and complete amino acid sequencing of P40 disclosed that it is structurally different from other T cells growth factors. So, it was named IL-9 based on its biological effects on both myeloid and lymphoid cells.[5] The identification and cloning was first done by Yang and colleagues as a mitogenic factor for a human megakaryoblastic leukemia.The same human cDNA was isolated again by cross-hybridization with the mouse IL-9 probe.[6] # Gene location The human IL-9 gene is located on the long arm of human chromosome 5 at band 5q31-32, a region which is not found in a number of patients with acquired chromosome 5q deletion syndrome.[7] # Protein structure IL-9 protein sequence contains 144 residues with a typical signal peptide of 18 amino acids.There is also the presence of 10 cysteines of the maturepolypeptide. 4 potential N-linked glycosylation sites are observed too.[6] The genomic structure of IL-9 consists of 10 exons. Among them, exons 3 and 7 encodes the extracellular domain, exon 8 encodes the transmembrane domain, and exons 9 and 10 encodes the cytoplasmic domain. Both the human and murine IL-9 receptors contains very high percentage of serine and proline in their cytoplasmic domain.[8] # Production Interleukin 33 (IL-33) induces IL-9 expression and secretion in T cells, which was confirmed by the results obtained in mice by using Human in vitro system.[9] Whereas the report of others confirms that TGF-β is an essential factor for IL-9 induction.[10] For the first time (Lars Blom,Britta C. Poulsen,Bettina M. Jensen,Anker Hansen and Lars K. Poulsen published a journal online in 2011 Jul 6),indicating that TGF-β may be important for production of IL-9 but it is not only the definite requirement for IL-9 induction, since cultures with IL-33 without TGF-β have noticeably increased secretion of IL-9, suggesting an important role of IL-33, even though that the effect was not found significant on the gene level.[11] # IL-9 expression The analysis of IL-9 expression in different types of tumours such as Large cell anaplastic lymphoma (LCAL) and Hodgkin's Disease (HD) by Northern blot analysis and in situ hybridization has showed that IL-9 is not involved as an autocrine growth factor in the pathogenesis of most B and T-cell lymphomas, but it may have a part in HD and LCAL autocrine growth. The further investigation could be done to conclude another probability, that, the in vivo overexpression of IL-9 might show the unique symptoms related to eosinophilia which was recently reported for Interleukin 5 positive cases of HD.[12] IL-9 was found to be the first physiological stimulus triggering BCL3 expression in T cells and mast cells by the analysis done in mouse.[13]	https://www.wikidoc.org/index.php/IL-9
1cece0701662c9e88a21e9226ce7d428a48dd218	wikidoc	Ibrexafungerp	Ibrexafungerp # Disclaimer WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here. # Black Box Warning # Overview Ibrexafungerp is a triterpenoid antifungal that is FDA approved for the treatment of vulvovaginal candidiasis. There is a Black Box Warning for this drug as shown here. Common adverse reactions include nausea, dizziness, diarrhea, vomiting, and abdominal pain. # Adult Indications and Dosage ## FDA-Labeled Indications and Dosage (Adult) Treatment of VVC - 300 mg Ibrexafungerp given 12 hours apart (600 mg in a day) for adult and post-menarchal pediatric females for one day of treatment. - Total of four 150 mg tablets each day, two tablets every 12 hours for one day. Reduction in the Incidence of RVVC - 300 mg Ibrexafungerp given 12 hours apart (600 mg) for adult and post-menarchal pediatric females for one day. - Dosages are given monthly for a total of 6 consecutive months of treatment. ## Off-Label Use and Dosage (Adult) ### Guideline-Supported Use There is limited information regarding Off-Label Guideline-Supported Use of Ibrexafungerp in adult patients. ### Non–Guideline-Supported Use There is limited information regarding Off-Label Non–Guideline-Supported Use of Ibrexafungerp in adult patients. # Pediatric Indications and Dosage ## FDA-Labeled Indications and Dosage (Pediatric) There is limited information regarding Ibrexafungerp FDA-Labeled Indications and Dosage (Pediatric) in the drug label. ## Off-Label Use and Dosage (Pediatric) ### Guideline-Supported Use There is limited information regarding Off-Label Guideline-Supported Use of Ibrexafungerp in pediatric patients. ### Non–Guideline-Supported Use There is limited information regarding Off-Label Non–Guideline-Supported Use of Ibrexafungerp in pediatric patients. # Contraindications - Pregnancy. - Hypersensitive patients towards Ibrexafungerp. # Warnings Risk of Embryo-Fetal Toxicity - Ibrexafungerp may cause fetal harm causing it to be contradicted in pregnancy. - Absent ear pinna, absent forelimb, thoracogastroschisis, and absent hindpaw were some of the fetal malformations observed in pregnant rabbits given dosages that were greater or equal to 5 times the recommended dosage for humans. - Advise female patients to take a pregnancy test before initiation of Ibrexafungerp treatment. - Monitor a females pregnancy status throughout the treatment to ensure that female is not pregnant during treatment. - Advise females of reproductive potential to use effective contraceptive methods during and for 4 days after the last dose of Ibrexafungerp treatment. # Adverse Reactions ## Clinical Trials Experience Clinical Trials Experience - Because clinical trials are conducted under widely varying conditions and durations of follow up, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Treatment of VVC - Trial 1 and 2 was made up of a population pool of 545 patients that were post-menarchal females with VVC. - Patients were mostly White (68%) and ranged from 18 years of age to 76 years of age. - Patients were given 300 mg of Ibrexafungerp 12 hours apart for one day (twice in the day). - No serious adverse reactions reported by patients in the study. - 2 patients had to discontinue Ibrexafungerp treatment due to dizziness and vomiting. Table 1 summarizes Adverse Reactions with Rates ≥2% in BREXAFEMME-Treated Patients with VVC in Trials 1 and 2. Insert Table 1 Other Adverse Reactions - Flatulence, elevated transaminases, dysmenorrhea, rash/hypersensitivity reaction, and vaginal bleeding were also observed in Trial 1 and Trial 2. Reduction in the Incidence of RVVC - Trial 3 study was made up of a population pool of 130 patients that were post-menarchal females with RVVC. - Patient population was mostly White (92%) and had ages ranging from 18 to 65 years of age. - Patients were given 300 mg of Ibrexafungerp 12 hours apart for one day monthly for 6 consecutive months. - No discontinuation or serious adverse reactions reported by patients in this trial. Table 2 summarizes Adverse Reactions with Rates ≥2% in BREXAFEMME-Treated Patients with RVVC in Trial 3. Insert Table 2 ## Postmarketing Experience There is limited information regarding Ibrexafungerp Postmarketing Experience in the drug label. # Drug Interactions - A substrate of CYP3A4 is Ibrexafungerp. - Safety and efficacy of Ibrexafungerp can be altered, specifically plasma concentrations, by drugs that induce or inhibit CYP3A. - P-gp, CYP3A4, and OATP1B3 transporter can be inhibited by Ibrexafungerp. - Pharmacokinetic differences of P-gp, CYP3A4, and OATP1B3 transporters are not clinically significant during short treatment of VVC using Ibrexafungerp. Table 3 summarizes Effect of Coadministered Drugs on Ibrexafungerp Pharmacokinetics. Insert Table 3 # Use in Specific Populations ### Pregnancy Pregnancy Category (FDA): Fetal harm may occur with Ibrexafungerp based on animal studies. Data on pregnant humans is insufficient when looking into Ibrexafungerp effects on any drug-associated risks of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Absent ear pinna, absent forelimb, thoracogastroschisis, and absent hindpaw were some of the fetal malformations observed in pregnant rabbits given dosages that were greater or equal to 5 times the recommended dosage for humans (25 mg/kg/day of Ibrexafungerp). Increased litter incidence was observed in pregant rabbits receiving 50 mg/kg/day of Ibrexafungerp. Pregnant rats did not have any fetal malformations or changes in embryo-fetal survival or fetal body weights when given doses up to 50 mg/kg/day of Ibrexafungerp. Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Ibrexafungerp in women who are pregnant. ### Labor and Delivery There is no FDA guidance on use of Ibrexafungerp during labor and delivery. ### Nursing Mothers No current data has been done on the effects of Ibrexafungerp on the breastfed infant and the effects on milk production in women when treated with Ibrexafungerp. Advise nursing patients about any potential adverse effects caused by Ibrexafungerp on the child. ### Pediatric Use Post-menarchal pediatric patients usage of Ibrexafungerp is supported by clinical studies conducted on dult non-pregnant women with additional pharmacokinetic and safety data from post-menarchal pediatric females. ### Geriatic Use When looking at the pharmacokinetics of geriatric patients compared to younger adults, there are no clinically meaningful differences. ### Gender There is no FDA guidance on the use of Ibrexafungerp with respect to specific gender populations. ### Race There is no FDA guidance on the use of Ibrexafungerp with respect to specific racial populations. ### Renal Impairment There is no FDA guidance on the use of Ibrexafungerp in patients with renal impairment. ### Hepatic Impairment Patients with mild or moderate hepatic impairment do not require dosage adjustment to Ibrexafungerp treatment. ### Females of Reproductive Potential and Males Fetal harm may occur when Ibrexafungerp is given to pregnant females. Advise female patients with reproductive potential to take a pregnancy test before and during Ibrexafungerp treatment. Advise female patients with reproductive potential to use effective contraception during and 4 days after Ibrexafungerp treatment for VVC. Advise female patients with reproductive potential to use effective contraception during 6 month treatment to reduce incidence of RVVC and 4 days after Ibrexafungerp treatment. ### Immunocompromised Patients There is no FDA guidance one the use of Ibrexafungerp in patients who are immunocompromised. # Administration and Monitoring ### Administration There is limited information regarding Ibrexafungerp Administration in the drug label. ### Monitoring Dosage Modifications in Patients due to Concomitant Use of a Strong Inhibitor of Cytochrome P450 Isoenzymes (CYP) 3A - Give 150 mg Ibrexafungerp 12 hours apart for one day with concomitant use of a strong CYP3A inhibitor. - Concomitant use of a weak or moderate CYP3A inhibitor with Ibrexafungerp did not require a dosage adjustment. - Verify a female patient with reproductive success is not pregnant before or during Ibrexafungerp treatment. # IV Compatibility There is limited information regarding the compatibility of Ibrexafungerp and IV administrations. # Overdosage - No experience of overdosage of Ibrexafungerp. - No specific antidote for Ibrexafungerp. # Pharmacology There is limited information regarding Ibrexafungerp Pharmacology in the drug label. ## Mechanism of Action - Ibrexafungerp is a triterpenoid antifungal drug. ## Structure - The empirical formula of Ibrexafungerp is C44H67N5O4 - C6H8O7. - The molecular weight of Ibrexafungerp is 922.18 grams. Insert Structure ## Pharmacodynamics - Ibrexafungerp pharmacodynamic responses are unknown. Cardiac Electrophysiology - QTc interval is not prolonged by ibrexafungerp at a concentration of 5 times or greater than that achieved after a single day 300 mg twice daily dose. ## Pharmacokinetics - When given a single dose administration from 10 to 1600 mg of Ibrexafungerp, the Cmax and AUC of Ibrexafungerp increased approximately dose-proportionally. - When given multiple dose 300-800 mg of Ibrexafungerp, the Cmax and AUC of Ibrexafungerp increased approximately dose-proportionally. - 6832 nghr/mL was the mean AUC 0-24 exposure when patients with VCC were given 300 mg twice a day for 2 doses of Ibrexafungerp under fasted conditions. - 435 ng/mL was the mean Cmax when patients with VCC were given 300 mg twice a day for 2 doses of Ibrexafungerp under fasted conditions. - 9867 nghr/mL was the mean AUC 0-24 exposure when patients with VCC were given 300 mg twice a day for 2 doses of Ibrexafungerp under fed conditions. - 629 ng/mL was the mean Cmax when patients with VCC were given 300 mg twice a day for 2 doses of Ibrexafungerp under fed conditions. Absorption - After single and multiple dosing, maximum plasma concentrations occurs from 4 to 6 hours for Ibrexafungerp. Effect of Food - There was a 32% increase in Cmax for Ibrexafungerp with a high fat meal when compared to fasted conditions. - There was a 38% increase in AUC for Ibrexafungerp with a high fat meal when compared to fasted conditions. - Changes in exposure are not considered clinically significant. Distribution - For Ibrexafungerp, 600 L is the mean steady state volume of distribution. - Ibrexafungerp is highly protein bound. Elimination - Biliary excretion and metabolism are primary methods in eliminating Ibrexafungerp. - For Ibrexafungerp, 20 hours is the elimination half-life. Metabolism - CYP3A4 hydroxylates Ibrexafungerp in vitro studies,followed by glucuronidation and sulfation of a hydroxylated inactive metabolite Excretion - 90% of the radioactive dose of Ibrexafungerp was recovered in feces when patients were given radio-labeled ibrexafungerp orally. - 51% of the radioactive dose of Ibrexafungerp that was recovered in feces, was found unchanged when patients were given radio-labeled ibrexafungerp orally. - 1% of the radioactive dose of Ibrexafungerp was recovered in urine when patients were given radio-labeled ibrexafungerp orally. Specific Populations Post-Menarchal Pediatric Females and Geriatric Patients - For Ibrexafungerp, geriatric patients and post-menarchal pediatric females did not experience changes to pharmacokinetics. Patients with Hepatic Impairment - Patients with mild to moderate hepatic impairment did not experience changes to pharmacokinetics when compared to healthy patients. Drug Interaction Studies - The substrate of P-gp and CYP3A4 is Ibrexafungerp. - P-gp transporter, CYP2C8, OATP1B3 transporter, and CYP3A4 are inhibited by Ibrexafungerp. - CYP3A4 is not induced by Ibrexafungerp. Effect of Coadministered Drugs on Ibrexafungerp Pharmacokinetics Strong CYP3A4 Inhibitor: - The was a 5.8-fold increase of AUC in Ibrexafungerp when coadministered with Ketoconazole, a strong CYP3A4 and P-gp inhibitor. - The was a 2.5-fold increase of Cmax in Ibrexafungerp when coadministered with Ketoconazole, a strong CYP3A4 and P-gp inhibitor. Moderate CYP3A4 Inhibitor: - The was a 2.5-fold increase of AUC in Ibrexafungerp when coadministered with Diltiazem. - The was a 2.2-fold increase of Cmax in Ibrexafungerp when coadministered with Diltiazem. - Exposure changes are not clinically significant. Proton Pump Inhibitor: - The was a 25% decrease of AUC in Ibrexafungerp when coadministered with Pantoprazole. - The was a 22% decrease of Cmax in Ibrexafungerp when coadministered with Pantoprazole. - Exposure changes are not clinically significant. Effect of Ibrexafungerp on the Pharmacokinetics of Coadministered Drugs CYP2C8 substrates: - The C max or AUC 0-inf of Rosiglitazone were not increased by Ibrexafungerp. CYP3A4 substrates: - Ibrexafungerp caused a 1.4-fold increase in the AUC 0-i of the P-gp substrate tacrolimus and CYP3A4. - Ibrexafungerp had no effects on the C max of the P-gp substrate tacrolimus and CYP3A4. P-gp substrates: - Ibrexafungerp caused a 1.4-fold increase in the AUC 0-i of the P-gp substrate dabigatran. - Ibrexafungerp caused a 1.25-fold increase in the Cmax of the P-gp substrate dabigatran. OATP1B3 transporters: - Ibrexafungerp caused a 2.8-fold increase in the AUC 0-i of the OATP1B3 transporter substrate pravastatin. - Ibrexafungerp caused a 3.5-fold increase in the Cmax of the OATP1B3 transporter substrate pravastatin. ## Nonclinical Toxicology Carcinogenesis - No carcinogenicity studies have been conducted on Ibrexafungerp. Mutagenesis - In vitro chromosomal aberration assay, vitro bacterial reverse mutation assay, and vivo bone marrow micronucleus assay, no clastogenic or mutagenic effects on rats were detected. Impairment of Fertility - When looking at male and female fertility study in rats, fertility was not impaired in either sex when given doses up to 80 mg/kg/day Ibrexafungerp. Animal Toxicity and/or Pharmacology - There were signs in rats of marked, but reversible, phospholipidosis, marked irritation and metaplasia in gastric mucosa, foamy histiocytes in alveolar tissue in the lung and labored breathing, and peripheral nerve degeneration accompanied by hind-limb paralysis when given does of up to 80 mg/kg/day of Ibrexafungerp for a 26 week period. # Clinical Studies Treatment of VVC - The safety and efficacy of Ibrexafungerp was tested in Trial 1 and 2 clinical studies. - Patients, with VVC, were given two 150 mg tablets per dose, administered 12 hours apart for a single day. - VVC diagnosis was defined as minimum composite vulvovaginal signs and symptoms (VSS) score of ≥4 with at least two signs or symptoms having a score of 2 (moderate) or greater. It also includes a positive microscopic examination with 10% KOH in a vaginal sample revealing yeast forms (hyphae/pseudohyphae) or budding yeasts, and (c) normal vaginal pH (≤4.5). - Trial 1 had a patient population that consisted of 100 patients who received a placebo and 190 patients treated with Ibrexafungerp. - The patient population had an average age of 34 years of age, majority White (81%), and an average BMI of 26. - 9 was the median VSS score of Trial 1 patients. - 92% of subjects in Trial 1 were culture-positive with C. albicans. - Trial 2 had a patient population that consisted of 89 patients who received a placebo and 189 patients treated with Ibrexafungerp. - The patient population had an average age of 34 years of age, majority White (81%), and an average BMI of 26. - 10 was the median VSS score of Trial 1 patients. - 89% of subjects in Trial 1 were culture-positive with C. albicans. Table 4 summarizes Clinical and Mycological Response in Post-menarchal Females with VVC in Trials 1 and 2, MITT Population. Insert Table 4 Reduction in the Incidence of RVVC - Trial 3 clinical study looked into the safety and efficacy of Ibrexafungerp when patients were given two 150 mg tablets of Ibrexafungerp 12 hours apart for one day. - Patients were either part of the group that received double-blind Ibrexafungerp or the group that received the placebo. - The trial was a single-day treatment repeated every 4 weeks for a total of 6 single-day treatments. - The patient population consisted of 130 patients who received the placebo and 130 patients who received Ibrexafungerp. - The patient population was mostly White (90%), with an average age of 34, and an average BMI of 25. - Clinical success was used to determine the efficacy of Ibrexafungerp. - Clinical success is defined as subjects with No Culture Proven, Presumed or Suspected Recurrence of VVC requiring antifungal therapy up to TOC at Week 24. Table 5 summarizes Clinical and Mycological Response in Post-menarchal Females with RVVC in Trial 3, ITT Population. Insert Table 5 # How Supplied - 150 mg of Ibrexafungerp per tablet. - Ibrexafungerp are purple, biconvex shaped tablets. ## Storage - Store Ibrexafungerp at 20°C to 25°C. - It is permitted if there is brief exposure of Ibrexafungerp tablets to 15°C to 30°C. # Images ## Drug Images ## Package and Label Display Panel # Patient Counseling Information Risk of Embryo-Fetal Toxicity - Ibrexafungerp is contraindicated in pregnancy due to the potential it has to cause harm to the fetus. - Advise female patients with potential to reproduce to take a pregnancy test before to confirm patient is not pregnant. - Advise female patients with potential to reproduce to reassess pregnancy status during Ibrexafungerp treatment. - Advise female patients with reproductive potential to use effective contraception during and 4 days after Ibrexafungerp treatment for VVC. - Advise female patients with reproductive potential to use effective contraception during 6 month treatment to reduce incidence of RVVC and 4 days after Ibrexafungerp treatment. - Advise female patients to inform doctor if they have a suspected or know pregnancy during Ibrexafungerp treatment. - Encourage female patients that took Ibrexafungerp during pregnancy to report their pregnancy to SCYNEXIS, Inc. at 1-888-982-7299. Important Administration Instructions - One dose for patients using Ibrexafungerp to treat VVC is 2 tablets. - Total treatment should be two doses (4 tablets) taken approximately 12 hours apart for patients using Ibrexafungerp to treat VVC. - 6 months is total treatment time for patients using Ibrexafungerp to reduce the incidence of RVVC. - Two tablets of Ibrexafungerp should be taken 12 hours apart monthly for a total of 6 months. - If 2 tablets of Ibrexafungerp are taken in the morning, then 2 more tablets should be taken in the evening of the same day. - If 2 tablets of Ibrexafungerp are taken in the afternoon, then 2 more tablets should be taken in the morning of the following day. - Ibrexafungerp tablets can be taken with or without food. Concomitant Medications - Advise patients that use of other medications with Ibrexafungerp can cause increase or decrease blood concentrations of Ibrexafungerp. - Advise patients that use of other medications with Ibrexafungerp can cause increase or decrease blood concentrations of other medications. # Precautions with Alcohol Alcohol-Ibrexafungerp interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication. # Brand Names - Brexafemme # Look-Alike Drug Names There is limited information regarding Ibrexafungerp Look-Alike Drug Names in the drug label. # Drug Shortage Status # Price	Ibrexafungerp Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Tejasvi Aryaputra # Disclaimer WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here. # Black Box Warning # Overview Ibrexafungerp is a triterpenoid antifungal that is FDA approved for the treatment of vulvovaginal candidiasis. There is a Black Box Warning for this drug as shown here. Common adverse reactions include nausea, dizziness, diarrhea, vomiting, and abdominal pain. # Adult Indications and Dosage ## FDA-Labeled Indications and Dosage (Adult) Treatment of VVC - 300 mg Ibrexafungerp given 12 hours apart (600 mg in a day) for adult and post-menarchal pediatric females for one day of treatment. - Total of four 150 mg tablets each day, two tablets every 12 hours for one day. Reduction in the Incidence of RVVC - 300 mg Ibrexafungerp given 12 hours apart (600 mg) for adult and post-menarchal pediatric females for one day. - Dosages are given monthly for a total of 6 consecutive months of treatment. ## Off-Label Use and Dosage (Adult) ### Guideline-Supported Use There is limited information regarding Off-Label Guideline-Supported Use of Ibrexafungerp in adult patients. ### Non–Guideline-Supported Use There is limited information regarding Off-Label Non–Guideline-Supported Use of Ibrexafungerp in adult patients. # Pediatric Indications and Dosage ## FDA-Labeled Indications and Dosage (Pediatric) There is limited information regarding Ibrexafungerp FDA-Labeled Indications and Dosage (Pediatric) in the drug label. ## Off-Label Use and Dosage (Pediatric) ### Guideline-Supported Use There is limited information regarding Off-Label Guideline-Supported Use of Ibrexafungerp in pediatric patients. ### Non–Guideline-Supported Use There is limited information regarding Off-Label Non–Guideline-Supported Use of Ibrexafungerp in pediatric patients. # Contraindications - Pregnancy. - Hypersensitive patients towards Ibrexafungerp. # Warnings Risk of Embryo-Fetal Toxicity - Ibrexafungerp may cause fetal harm causing it to be contradicted in pregnancy. - Absent ear pinna, absent forelimb, thoracogastroschisis, and absent hindpaw were some of the fetal malformations observed in pregnant rabbits given dosages that were greater or equal to 5 times the recommended dosage for humans. - Advise female patients to take a pregnancy test before initiation of Ibrexafungerp treatment. - Monitor a females pregnancy status throughout the treatment to ensure that female is not pregnant during treatment. - Advise females of reproductive potential to use effective contraceptive methods during and for 4 days after the last dose of Ibrexafungerp treatment. # Adverse Reactions ## Clinical Trials Experience Clinical Trials Experience - Because clinical trials are conducted under widely varying conditions and durations of follow up, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Treatment of VVC - Trial 1 and 2 was made up of a population pool of 545 patients that were post-menarchal females with VVC. - Patients were mostly White (68%) and ranged from 18 years of age to 76 years of age. - Patients were given 300 mg of Ibrexafungerp 12 hours apart for one day (twice in the day). - No serious adverse reactions reported by patients in the study. - 2 patients had to discontinue Ibrexafungerp treatment due to dizziness and vomiting. Table 1 summarizes Adverse Reactions with Rates ≥2% in BREXAFEMME-Treated Patients with VVC in Trials 1 and 2. Insert Table 1 Other Adverse Reactions - Flatulence, elevated transaminases, dysmenorrhea, rash/hypersensitivity reaction, and vaginal bleeding were also observed in Trial 1 and Trial 2. Reduction in the Incidence of RVVC - Trial 3 study was made up of a population pool of 130 patients that were post-menarchal females with RVVC. - Patient population was mostly White (92%) and had ages ranging from 18 to 65 years of age. - Patients were given 300 mg of Ibrexafungerp 12 hours apart for one day monthly for 6 consecutive months. - No discontinuation or serious adverse reactions reported by patients in this trial. Table 2 summarizes Adverse Reactions with Rates ≥2% in BREXAFEMME-Treated Patients with RVVC in Trial 3. Insert Table 2 ## Postmarketing Experience There is limited information regarding Ibrexafungerp Postmarketing Experience in the drug label. # Drug Interactions - A substrate of CYP3A4 is Ibrexafungerp. - Safety and efficacy of Ibrexafungerp can be altered, specifically plasma concentrations, by drugs that induce or inhibit CYP3A. - P-gp, CYP3A4, and OATP1B3 transporter can be inhibited by Ibrexafungerp. - Pharmacokinetic differences of P-gp, CYP3A4, and OATP1B3 transporters are not clinically significant during short treatment of VVC using Ibrexafungerp. Table 3 summarizes Effect of Coadministered Drugs on Ibrexafungerp Pharmacokinetics. Insert Table 3 # Use in Specific Populations ### Pregnancy Pregnancy Category (FDA): Fetal harm may occur with Ibrexafungerp based on animal studies. Data on pregnant humans is insufficient when looking into Ibrexafungerp effects on any drug-associated risks of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Absent ear pinna, absent forelimb, thoracogastroschisis, and absent hindpaw were some of the fetal malformations observed in pregnant rabbits given dosages that were greater or equal to 5 times the recommended dosage for humans (25 mg/kg/day of Ibrexafungerp). Increased litter incidence was observed in pregant rabbits receiving 50 mg/kg/day of Ibrexafungerp. Pregnant rats did not have any fetal malformations or changes in embryo-fetal survival or fetal body weights when given doses up to 50 mg/kg/day of Ibrexafungerp. Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Ibrexafungerp in women who are pregnant. ### Labor and Delivery There is no FDA guidance on use of Ibrexafungerp during labor and delivery. ### Nursing Mothers No current data has been done on the effects of Ibrexafungerp on the breastfed infant and the effects on milk production in women when treated with Ibrexafungerp. Advise nursing patients about any potential adverse effects caused by Ibrexafungerp on the child. ### Pediatric Use Post-menarchal pediatric patients usage of Ibrexafungerp is supported by clinical studies conducted on dult non-pregnant women with additional pharmacokinetic and safety data from post-menarchal pediatric females. ### Geriatic Use When looking at the pharmacokinetics of geriatric patients compared to younger adults, there are no clinically meaningful differences. ### Gender There is no FDA guidance on the use of Ibrexafungerp with respect to specific gender populations. ### Race There is no FDA guidance on the use of Ibrexafungerp with respect to specific racial populations. ### Renal Impairment There is no FDA guidance on the use of Ibrexafungerp in patients with renal impairment. ### Hepatic Impairment Patients with mild or moderate hepatic impairment do not require dosage adjustment to Ibrexafungerp treatment. ### Females of Reproductive Potential and Males Fetal harm may occur when Ibrexafungerp is given to pregnant females. Advise female patients with reproductive potential to take a pregnancy test before and during Ibrexafungerp treatment. Advise female patients with reproductive potential to use effective contraception during and 4 days after Ibrexafungerp treatment for VVC. Advise female patients with reproductive potential to use effective contraception during 6 month treatment to reduce incidence of RVVC and 4 days after Ibrexafungerp treatment. ### Immunocompromised Patients There is no FDA guidance one the use of Ibrexafungerp in patients who are immunocompromised. # Administration and Monitoring ### Administration There is limited information regarding Ibrexafungerp Administration in the drug label. ### Monitoring Dosage Modifications in Patients due to Concomitant Use of a Strong Inhibitor of Cytochrome P450 Isoenzymes (CYP) 3A - Give 150 mg Ibrexafungerp 12 hours apart for one day with concomitant use of a strong CYP3A inhibitor. - Concomitant use of a weak or moderate CYP3A inhibitor with Ibrexafungerp did not require a dosage adjustment. - Verify a female patient with reproductive success is not pregnant before or during Ibrexafungerp treatment. # IV Compatibility There is limited information regarding the compatibility of Ibrexafungerp and IV administrations. # Overdosage - No experience of overdosage of Ibrexafungerp. - No specific antidote for Ibrexafungerp. # Pharmacology There is limited information regarding Ibrexafungerp Pharmacology in the drug label. ## Mechanism of Action - Ibrexafungerp is a triterpenoid antifungal drug. ## Structure - The empirical formula of Ibrexafungerp is C44H67N5O4 • C6H8O7. - The molecular weight of Ibrexafungerp is 922.18 grams. Insert Structure ## Pharmacodynamics - Ibrexafungerp pharmacodynamic responses are unknown. Cardiac Electrophysiology - QTc interval is not prolonged by ibrexafungerp at a concentration of 5 times or greater than that achieved after a single day 300 mg twice daily dose. ## Pharmacokinetics - When given a single dose administration from 10 to 1600 mg of Ibrexafungerp, the Cmax and AUC of Ibrexafungerp increased approximately dose-proportionally. - When given multiple dose 300-800 mg of Ibrexafungerp, the Cmax and AUC of Ibrexafungerp increased approximately dose-proportionally. - 6832 ng•hr/mL was the mean AUC 0-24 exposure when patients with VCC were given 300 mg twice a day for 2 doses of Ibrexafungerp under fasted conditions. - 435 ng/mL was the mean Cmax when patients with VCC were given 300 mg twice a day for 2 doses of Ibrexafungerp under fasted conditions. - 9867 ng•hr/mL was the mean AUC 0-24 exposure when patients with VCC were given 300 mg twice a day for 2 doses of Ibrexafungerp under fed conditions. - 629 ng/mL was the mean Cmax when patients with VCC were given 300 mg twice a day for 2 doses of Ibrexafungerp under fed conditions. Absorption - After single and multiple dosing, maximum plasma concentrations occurs from 4 to 6 hours for Ibrexafungerp. Effect of Food - There was a 32% increase in Cmax for Ibrexafungerp with a high fat meal when compared to fasted conditions. - There was a 38% increase in AUC for Ibrexafungerp with a high fat meal when compared to fasted conditions. - Changes in exposure are not considered clinically significant. Distribution - For Ibrexafungerp, 600 L is the mean steady state volume of distribution. - Ibrexafungerp is highly protein bound. Elimination - Biliary excretion and metabolism are primary methods in eliminating Ibrexafungerp. - For Ibrexafungerp, 20 hours is the elimination half-life. Metabolism - CYP3A4 hydroxylates Ibrexafungerp in vitro studies,followed by glucuronidation and sulfation of a hydroxylated inactive metabolite Excretion - 90% of the radioactive dose of Ibrexafungerp was recovered in feces when patients were given radio-labeled ibrexafungerp orally. - 51% of the radioactive dose of Ibrexafungerp that was recovered in feces, was found unchanged when patients were given radio-labeled ibrexafungerp orally. - 1% of the radioactive dose of Ibrexafungerp was recovered in urine when patients were given radio-labeled ibrexafungerp orally. Specific Populations Post-Menarchal Pediatric Females and Geriatric Patients - For Ibrexafungerp, geriatric patients and post-menarchal pediatric females did not experience changes to pharmacokinetics. Patients with Hepatic Impairment - Patients with mild to moderate hepatic impairment did not experience changes to pharmacokinetics when compared to healthy patients. Drug Interaction Studies - The substrate of P-gp and CYP3A4 is Ibrexafungerp. - P-gp transporter, CYP2C8, OATP1B3 transporter, and CYP3A4 are inhibited by Ibrexafungerp. - CYP3A4 is not induced by Ibrexafungerp. Effect of Coadministered Drugs on Ibrexafungerp Pharmacokinetics Strong CYP3A4 Inhibitor: - The was a 5.8-fold increase of AUC in Ibrexafungerp when coadministered with Ketoconazole, a strong CYP3A4 and P-gp inhibitor. - The was a 2.5-fold increase of Cmax in Ibrexafungerp when coadministered with Ketoconazole, a strong CYP3A4 and P-gp inhibitor. Moderate CYP3A4 Inhibitor: - The was a 2.5-fold increase of AUC in Ibrexafungerp when coadministered with Diltiazem. - The was a 2.2-fold increase of Cmax in Ibrexafungerp when coadministered with Diltiazem. - Exposure changes are not clinically significant. Proton Pump Inhibitor: - The was a 25% decrease of AUC in Ibrexafungerp when coadministered with Pantoprazole. - The was a 22% decrease of Cmax in Ibrexafungerp when coadministered with Pantoprazole. - Exposure changes are not clinically significant. Effect of Ibrexafungerp on the Pharmacokinetics of Coadministered Drugs CYP2C8 substrates: - The C max or AUC 0-inf of Rosiglitazone were not increased by Ibrexafungerp. CYP3A4 substrates: - Ibrexafungerp caused a 1.4-fold increase in the AUC 0-i of the P-gp substrate tacrolimus and CYP3A4. - Ibrexafungerp had no effects on the C max of the P-gp substrate tacrolimus and CYP3A4. P-gp substrates: - Ibrexafungerp caused a 1.4-fold increase in the AUC 0-i of the P-gp substrate dabigatran. - Ibrexafungerp caused a 1.25-fold increase in the Cmax of the P-gp substrate dabigatran. OATP1B3 transporters: - Ibrexafungerp caused a 2.8-fold increase in the AUC 0-i of the OATP1B3 transporter substrate pravastatin. - Ibrexafungerp caused a 3.5-fold increase in the Cmax of the OATP1B3 transporter substrate pravastatin. ## Nonclinical Toxicology Carcinogenesis - No carcinogenicity studies have been conducted on Ibrexafungerp. Mutagenesis - In vitro chromosomal aberration assay, vitro bacterial reverse mutation assay, and vivo bone marrow micronucleus assay, no clastogenic or mutagenic effects on rats were detected. Impairment of Fertility - When looking at male and female fertility study in rats, fertility was not impaired in either sex when given doses up to 80 mg/kg/day Ibrexafungerp. Animal Toxicity and/or Pharmacology - There were signs in rats of marked, but reversible, phospholipidosis, marked irritation and metaplasia in gastric mucosa, foamy histiocytes in alveolar tissue in the lung and labored breathing, and peripheral nerve degeneration accompanied by hind-limb paralysis when given does of up to 80 mg/kg/day of Ibrexafungerp for a 26 week period. # Clinical Studies Treatment of VVC - The safety and efficacy of Ibrexafungerp was tested in Trial 1 and 2 clinical studies. - Patients, with VVC, were given two 150 mg tablets per dose, administered 12 hours apart for a single day. - VVC diagnosis was defined as minimum composite vulvovaginal signs and symptoms (VSS) score of ≥4 with at least two signs or symptoms having a score of 2 (moderate) or greater. It also includes a positive microscopic examination with 10% KOH in a vaginal sample revealing yeast forms (hyphae/pseudohyphae) or budding yeasts, and (c) normal vaginal pH (≤4.5). - Trial 1 had a patient population that consisted of 100 patients who received a placebo and 190 patients treated with Ibrexafungerp. - The patient population had an average age of 34 years of age, majority White (81%), and an average BMI of 26. - 9 was the median VSS score of Trial 1 patients. - 92% of subjects in Trial 1 were culture-positive with C. albicans. - Trial 2 had a patient population that consisted of 89 patients who received a placebo and 189 patients treated with Ibrexafungerp. - The patient population had an average age of 34 years of age, majority White (81%), and an average BMI of 26. - 10 was the median VSS score of Trial 1 patients. - 89% of subjects in Trial 1 were culture-positive with C. albicans. Table 4 summarizes Clinical and Mycological Response in Post-menarchal Females with VVC in Trials 1 and 2, MITT Population. Insert Table 4 Reduction in the Incidence of RVVC - Trial 3 clinical study looked into the safety and efficacy of Ibrexafungerp when patients were given two 150 mg tablets of Ibrexafungerp 12 hours apart for one day. - Patients were either part of the group that received double-blind Ibrexafungerp or the group that received the placebo. - The trial was a single-day treatment repeated every 4 weeks for a total of 6 single-day treatments. - The patient population consisted of 130 patients who received the placebo and 130 patients who received Ibrexafungerp. - The patient population was mostly White (90%), with an average age of 34, and an average BMI of 25. - Clinical success was used to determine the efficacy of Ibrexafungerp. - Clinical success is defined as subjects with No Culture Proven, Presumed or Suspected Recurrence of VVC requiring antifungal therapy up to TOC at Week 24. Table 5 summarizes Clinical and Mycological Response in Post-menarchal Females with RVVC in Trial 3, ITT Population. Insert Table 5 # How Supplied - 150 mg of Ibrexafungerp per tablet. - Ibrexafungerp are purple, biconvex shaped tablets. ## Storage - Store Ibrexafungerp at 20°C to 25°C. - It is permitted if there is brief exposure of Ibrexafungerp tablets to 15°C to 30°C. # Images ## Drug Images ## Package and Label Display Panel # Patient Counseling Information Risk of Embryo-Fetal Toxicity - Ibrexafungerp is contraindicated in pregnancy due to the potential it has to cause harm to the fetus. - Advise female patients with potential to reproduce to take a pregnancy test before to confirm patient is not pregnant. - Advise female patients with potential to reproduce to reassess pregnancy status during Ibrexafungerp treatment. - Advise female patients with reproductive potential to use effective contraception during and 4 days after Ibrexafungerp treatment for VVC. - Advise female patients with reproductive potential to use effective contraception during 6 month treatment to reduce incidence of RVVC and 4 days after Ibrexafungerp treatment. - Advise female patients to inform doctor if they have a suspected or know pregnancy during Ibrexafungerp treatment. - Encourage female patients that took Ibrexafungerp during pregnancy to report their pregnancy to SCYNEXIS, Inc. at 1-888-982-7299. Important Administration Instructions - One dose for patients using Ibrexafungerp to treat VVC is 2 tablets. - Total treatment should be two doses (4 tablets) taken approximately 12 hours apart for patients using Ibrexafungerp to treat VVC. - 6 months is total treatment time for patients using Ibrexafungerp to reduce the incidence of RVVC. - Two tablets of Ibrexafungerp should be taken 12 hours apart monthly for a total of 6 months. - If 2 tablets of Ibrexafungerp are taken in the morning, then 2 more tablets should be taken in the evening of the same day. - If 2 tablets of Ibrexafungerp are taken in the afternoon, then 2 more tablets should be taken in the morning of the following day. - Ibrexafungerp tablets can be taken with or without food. Concomitant Medications - Advise patients that use of other medications with Ibrexafungerp can cause increase or decrease blood concentrations of Ibrexafungerp. - Advise patients that use of other medications with Ibrexafungerp can cause increase or decrease blood concentrations of other medications. # Precautions with Alcohol Alcohol-Ibrexafungerp interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication. # Brand Names - Brexafemme # Look-Alike Drug Names There is limited information regarding Ibrexafungerp Look-Alike Drug Names in the drug label. # Drug Shortage Status # Price	https://www.wikidoc.org/index.php/Ibrexafungerp
5538f850e451446be48e313a1213ed1ccd6cc3b0	wikidoc	Ideal gas law	Ideal gas law The ideal gas law is the equation of state of a hypothetical ideal gas, first stated by Benoît Paul Émile Clapeyron in 1834. where The value of the ideal gas constant, R, is found to be as follows. The ideal gas law mathematically follows from a statistical mechanical treatment of primitive identical particles (point particles without internal structure) which do not interact, but exchange momentum (and hence kinetic energy) in elastic collisions. Since it neglects both molecular size and intermolecular attractions, the ideal gas law is most accurate for monoatomic gases at high temperatures and low pressures. The neglect of molecular size becomes less important for larger volumes, i.e., for lower pressures. The relative importance of intermolecular attractions diminishes with increasing thermal kinetic energy i.e., with increasing temperatures. More sophisticated equations of state, such as the van der Waals equation, allow deviations from ideality caused by molecular size and intermolecular forces to be taken into account. # Alternative forms As the amount of substance could be given in mass instead of moles, sometimes an alternative form of the ideal gas law is useful. The number of moles (n\, ) is equal to the mass (\, m ) divided by the molar mass (\, M ): Then, replacing \, n gives: from where This form of the ideal gas law is particularly useful because it links pressure, density \rho = m/V, and temperature in a unique formula independent from the quantity of the considered gas. In statistical mechanics the following molecular equation is derived from first principles: Here \,k is Boltzmann's constant, and \,N is the actual number of molecules, in contrast to the other formulation, which uses \,n, the number of moles. This relation implies that N\,k = nR, and the consistency of this result with experiment is a good check on the principles of statistical mechanics. From here we can notice that for an average particle mass of \mu times the atomic mass constant m_\mathrm{u} (i.e., the mass is \mu u) and since \rho = m/V , we find that the ideal gas law can be re-written as: One more equation involves density where: where M is the mass and D is the density. # Calculations # Derivations ## Empirical The ideal gas law can be derived from combining two empirical gas laws: the combined gas law and Avogadro's law. The combined gas law states that where C is a constant which is directly proportional to the amount of gas, n (Avogadro's law). The proportionality factor is the universal gas constant, R, i.e. C=nR. Hence the ideal gas law ## Theoretical The ideal gas law can also be derived from first principles using the kinetic theory of gases, in which several simplifying assumptions are made, chief among which are that the molecules, or atoms, of the gas are point masses, possessing mass but no significant volume, and undergo only elastic collisions with each other and the sides of the container in which both linear momentum and kinetic energy are conserved. ## Derivation from the statistical mechanics Let q = (qx, qy, qz) and p = (px, py, pz) denote the position vector and momentum vector of a particle of an ideal gas,respectively, and let F denote the net force on that particle, then \begin{align} \langle \mathbf{q} \cdot \mathbf{F} \rangle &= \Bigl\langle q_{x} \frac{dp_{x}}{dt} \Bigr\rangle + \Bigl\langle q_{y} \frac{dp_{y}}{dt} \Bigr\rangle + \Bigl\langle q_{z} \frac{dp_{z}}{dt} \Bigr\rangle\\ &=-\Bigl\langle q_{x} \frac{\partial H}{\partial q_x} \Bigr\rangle - \Bigl\langle q_{y} \frac{\partial H}{\partial q_y} \Bigr\rangle - \Bigl\langle q_{z} \frac{\partial H}{\partial q_z} \Bigr\rangle = -3k_{B} T, \end{align} where the first equality is Newton's second law, and the second line uses Hamilton's equations and the equipartition theorem. Summing over a system of N particles yields 3Nk_{B} T = - \biggl\langle \sum_{k=1}^{N} \mathbf{q}_{k} \cdot \mathbf{F}_{k} \biggr\rangle. By Newton's third law and the ideal gas assumption, the net force on the system is the force applied by the walls of their container, and this force is given by the pressure P of the gas. Hence -\biggl\langle\sum_{k=1}^{N} \mathbf{q}_{k} \cdot \mathbf{F}_{k}\biggr\rangle = P \oint_{\mathrm{surface}} \mathbf{q} \cdot \mathbf{dS}, where dS is the infinitesimal area element along the walls of the container. Since the divergence of the position vector q is \boldsymbol\nabla \cdot \mathbf{q} = \frac{\partial q_{x}}{\partial q_{x}} + \frac{\partial q_{y}}{\partial q_{y}} + \frac{\partial q_{z}}{\partial q_{z}} = 3, the divergence theorem implies that P \oint_{\mathrm{surface}} \mathbf{q} \cdot \mathbf{dS} = P \int_{\mathrm{volume}} \left( \boldsymbol\nabla \cdot \mathbf{q} \right) dV = 3PV, where dV is an infinitesimal volume within the container and V is the total volume of the container. Putting these equalities together yields 3Nk_{B} T = -\biggl\langle \sum_{k=1}^{N} \mathbf{q}_{k} \cdot \mathbf{F}_{k} \biggr\rangle = 3PV, which immediately implies the ideal gas law for N particles: PV = Nk_{B} T = nRT,\, where n=N/NA is the number of moles of gas and R=NAkB is the gas constant. The readers are referred to the comprehensive article Configuration integral (statistical mechanics) where an alternative statistical mechanics derivation of the ideal-gas law, using the relationship between the Helmholtz free energy and the partition function, but without using the equipartition theorem, is provided.	Ideal gas law The ideal gas law is the equation of state of a hypothetical ideal gas, first stated by Benoît Paul Émile Clapeyron in 1834. where The value of the ideal gas constant, R, is found to be as follows. The ideal gas law mathematically follows from a statistical mechanical treatment of primitive identical particles (point particles without internal structure) which do not interact, but exchange momentum (and hence kinetic energy) in elastic collisions. Since it neglects both molecular size and intermolecular attractions, the ideal gas law is most accurate for monoatomic gases at high temperatures and low pressures. The neglect of molecular size becomes less important for larger volumes, i.e., for lower pressures. The relative importance of intermolecular attractions diminishes with increasing thermal kinetic energy i.e., with increasing temperatures. More sophisticated equations of state, such as the van der Waals equation, allow deviations from ideality caused by molecular size and intermolecular forces to be taken into account. # Alternative forms As the amount of substance could be given in mass instead of moles, sometimes an alternative form of the ideal gas law is useful. The number of moles (<math>n\, </math>) is equal to the mass (<math>\, m </math>) divided by the molar mass (<math>\, M </math>): Then, replacing <math>\, n </math> gives: from where This form of the ideal gas law is particularly useful because it links pressure, density <math> \rho = m/V</math>, and temperature in a unique formula independent from the quantity of the considered gas. In statistical mechanics the following molecular equation is derived from first principles: Here <math>\,k</math> is Boltzmann's constant, and <math>\,N</math> is the actual number of molecules, in contrast to the other formulation, which uses <math>\,n</math>, the number of moles. This relation implies that <math>N\,k = nR</math>, and the consistency of this result with experiment is a good check on the principles of statistical mechanics. From here we can notice that for an average particle mass of <math> \mu </math> times the atomic mass constant <math>m_\mathrm{u}</math> (i.e., the mass is <math>\mu</math> u) and since <math> \rho = m/V </math>, we find that the ideal gas law can be re-written as: One more equation involves density where: where M is the mass and D is the density. # Calculations Template:Note label a. In an isentropic process, system entropy (Q) is constant. Under these conditions, P1 V1<math>\gamma</math> = P2 V2<math>\gamma</math>, where <math>\gamma</math> is defined as the heat capacity ratio, which is constant for an ideal gas. # Derivations ## Empirical The ideal gas law can be derived from combining two empirical gas laws: the combined gas law and Avogadro's law. The combined gas law states that where C is a constant which is directly proportional to the amount of gas, n (Avogadro's law). The proportionality factor is the universal gas constant, R, i.e. <math>C=nR</math>. Hence the ideal gas law ## Theoretical The ideal gas law can also be derived from first principles using the kinetic theory of gases, in which several simplifying assumptions are made, chief among which are that the molecules, or atoms, of the gas are point masses, possessing mass but no significant volume, and undergo only elastic collisions with each other and the sides of the container in which both linear momentum and kinetic energy are conserved. ## Derivation from the statistical mechanics Let q = (qx, qy, qz) and p = (px, py, pz) denote the position vector and momentum vector of a particle of an ideal gas,respectively, and let F denote the net force on that particle, then \begin{align} \langle \mathbf{q} \cdot \mathbf{F} \rangle &= \Bigl\langle q_{x} \frac{dp_{x}}{dt} \Bigr\rangle + \Bigl\langle q_{y} \frac{dp_{y}}{dt} \Bigr\rangle + \Bigl\langle q_{z} \frac{dp_{z}}{dt} \Bigr\rangle\\ &=-\Bigl\langle q_{x} \frac{\partial H}{\partial q_x} \Bigr\rangle - \Bigl\langle q_{y} \frac{\partial H}{\partial q_y} \Bigr\rangle - \Bigl\langle q_{z} \frac{\partial H}{\partial q_z} \Bigr\rangle = -3k_{B} T, \end{align} </math> where the first equality is Newton's second law, and the second line uses Hamilton's equations and the equipartition theorem. Summing over a system of N particles yields 3Nk_{B} T = - \biggl\langle \sum_{k=1}^{N} \mathbf{q}_{k} \cdot \mathbf{F}_{k} \biggr\rangle. </math> By Newton's third law and the ideal gas assumption, the net force on the system is the force applied by the walls of their container, and this force is given by the pressure P of the gas. Hence -\biggl\langle\sum_{k=1}^{N} \mathbf{q}_{k} \cdot \mathbf{F}_{k}\biggr\rangle = P \oint_{\mathrm{surface}} \mathbf{q} \cdot \mathbf{dS}, </math> where dS is the infinitesimal area element along the walls of the container. Since the divergence of the position vector q is \boldsymbol\nabla \cdot \mathbf{q} = \frac{\partial q_{x}}{\partial q_{x}} + \frac{\partial q_{y}}{\partial q_{y}} + \frac{\partial q_{z}}{\partial q_{z}} = 3, </math> the divergence theorem implies that P \oint_{\mathrm{surface}} \mathbf{q} \cdot \mathbf{dS} = P \int_{\mathrm{volume}} \left( \boldsymbol\nabla \cdot \mathbf{q} \right) dV = 3PV, </math> where dV is an infinitesimal volume within the container and V is the total volume of the container. Putting these equalities together yields 3Nk_{B} T = -\biggl\langle \sum_{k=1}^{N} \mathbf{q}_{k} \cdot \mathbf{F}_{k} \biggr\rangle = 3PV, </math> which immediately implies the ideal gas law for N particles: PV = Nk_{B} T = nRT,\, </math> where n=N/NA is the number of moles of gas and R=NAkB is the gas constant. The readers are referred to the comprehensive article Configuration integral (statistical mechanics) where an alternative statistical mechanics derivation of the ideal-gas law, using the relationship between the Helmholtz free energy and the partition function, but without using the equipartition theorem, is provided.	https://www.wikidoc.org/index.php/Ideal_gas_law
73b9b92816934d09c6151f9acb0a7fece82e66fb	wikidoc	Immature ovum	Immature ovum An immature ovum is a cell that goes through the process of oogenesis to become an ovum. It can be either an oogonium, oocyte and an ootid. An oocyte, in turn, can be either primary or secondary, depending on how far it has come in its process of meiosis. # Oogonium Oogonia are the cells that turn into primary oocytes in oogenesis. They are diploid, i.e. containing both pairs of homologous chromosomes. There are 23 chromosome pairs. Thus there are 46 chromosomes. Each chromosome, however, hasn't yet duplicated itself. Thus, there are only one chromatid on each chromosome, making the total quantity of chromatids 46. This is twice the number of chromosome pairs (2N). ## Timeline Oogonia are created in early embryonic life. All have turned into oogonia at late fetal age. # Primary oocyte The primary oocyte is defined by its process of ootidogenesis, which is meiosis. It has duplicated its DNA, so that each chromosome has two chomatids, i.e. 92 chromatids all in all (4N). When meiosis I is completed, one secondary oocyte and one polar body is created. ## Timeline Primary oocytes have been created in late fetal life. This is the stage where immature ova spend most of their lifetime, more specifically in prophase I of meiosis. The halt is called dictyate. Most degenerate by atresia, but a few go through ovulation, and that's the trigger to the next step. Thus, an immature ovum can spend up to ~55 years as a primary oocyte (the last ovulation before menopause). # Secondary oocyte The secondary oocyte is the cell that is formed by meiosis I in oogenesis. Thus, it has only one of each pair of homologous chromosomes. In other words, it is haploid. However, each chromosome still has two chromatids, making a total of 46 chromatids (2N). The secondary oocyte continues the second stage of meiosis (meiosis II), and the daughter cells are one ootid and one polar body. ## Timeline Secondary oocytes are the immature ovum shortly after ovulation, to fertilization, where it turns into an ootid. Thus, the time as a secondary oocyte is measured in days. ## Size The secondary oocyte is the largest cell in the body, and in humans is just visible to the naked eye. # Ootid An ootid is the haploid result of ootidogenesis. In oogenesis, it deosn't really have any significance in itself, since it is very similar to the ovum. However, it fills the purpose as the female counterpart of the male spermatid in spermatogenesis. Each chromosome is split between the two ootids, leaving only one chromatid per chromosome. Thus, there are 23 chromatids in total (1N). ## Timeline In other words, the ootid is the immature ovum from shortly after fertilization, but before complete maturation into an ovum. Thus, the time spent as an ootid is measured in minutes. # Ovum The ootid matures into an ovum.	Immature ovum An immature ovum is a cell that goes through the process of oogenesis to become an ovum. It can be either an oogonium, oocyte and an ootid. An oocyte, in turn, can be either primary or secondary, depending on how far it has come in its process of meiosis. ## Oogonium Oogonia are the cells that turn into primary oocytes in oogenesis[1]. They are diploid, i.e. containing both pairs of homologous chromosomes. There are 23 chromosome pairs. Thus there are 46 chromosomes. Each chromosome, however, hasn't yet duplicated itself. Thus, there are only one chromatid on each chromosome, making the total quantity of chromatids 46. This is twice the number of chromosome pairs (2N). ### Timeline Oogonia are created in early embryonic life. All have turned into oogonia at late fetal age. ## Primary oocyte The primary oocyte is defined by its process of ootidogenesis, which is meiosis[2]. It has duplicated its DNA, so that each chromosome has two chomatids, i.e. 92 chromatids all in all (4N). When meiosis I is completed, one secondary oocyte and one polar body is created. ### Timeline Primary oocytes have been created in late fetal life. This is the stage where immature ova spend most of their lifetime, more specifically in prophase I of meiosis. The halt is called dictyate. Most degenerate by atresia, but a few go through ovulation, and that's the trigger to the next step. Thus, an immature ovum can spend up to ~55 years as a primary oocyte (the last ovulation before menopause). ## Secondary oocyte The secondary oocyte is the cell that is formed by meiosis I in oogenesis[3]. Thus, it has only one of each pair of homologous chromosomes. In other words, it is haploid. However, each chromosome still has two chromatids, making a total of 46 chromatids (2N). The secondary oocyte continues the second stage of meiosis (meiosis II), and the daughter cells are one ootid and one polar body. ### Timeline Secondary oocytes are the immature ovum shortly after ovulation, to fertilization, where it turns into an ootid. Thus, the time as a secondary oocyte is measured in days. ### Size The secondary oocyte is the largest cell in the body, and in humans is just visible to the naked eye. ## Ootid An ootid is the haploid result of ootidogenesis[4]. In oogenesis, it deosn't really have any significance in itself, since it is very similar to the ovum. However, it fills the purpose as the female counterpart of the male spermatid in spermatogenesis. Each chromosome is split between the two ootids, leaving only one chromatid per chromosome. Thus, there are 23 chromatids in total (1N). ### Timeline In other words, the ootid is the immature ovum from shortly after fertilization, but before complete maturation into an ovum. Thus, the time spent as an ootid is measured in minutes. ## Ovum The ootid matures into an ovum.	https://www.wikidoc.org/index.php/Immature_ova
a2a0d16be3b3caa6c7aa71661ceb2312490afe24	wikidoc	Impact factor	Impact factor # Overview The Impact factor, often abbreviated IF, is a measure of the citations to science and social science journals. It is frequently used as a proxy for the importance of a journal to its field. # Overview The Impact factor was devised by Eugene Garfield, the founder of the Institute for Scientific Information, now part of Thomson, a large worldwide US-based publisher. Impact factors are calculated each year by Thomson Scientific for those journals which it indexes, and the factors and indices are published in Journal Citation Reports. Some related values, also calculated and published by the same organization, are: - the immediacy index: the number of citations the articles in a journal receive in a given year divided by the number of articles published. - the cited half-life: the median age of the articles that were cited in Journal Citation Reports each year. For example, if a journal's half-life in 2005 is 5, that means the citations from 2001-2005 are half of all the citations from that journal in 2005, and the other half of the citations precede 2001. - the aggregate impact factor for a subject category: it is calculated taking into account the number of citations to all journals in the subject category and the number of articles from all the journals in the subject category. These measures apply only to journals, not individual articles or individual scientists (unlike, say, the H-index). The relative number of citations an individual article receives is better viewed as citation impact. It is, however, possible to measure the Impact factor of the journals in which a particular person has published articles. This use is widespread, but controversial. Eugene Garfield warns about the "misuse in evaluating individuals" because there is "a wide variation from article to article within a single journal". Impact factors have a huge, but controversial, influence on the way published scientific research is perceived and evaluated. # Calculation The impact factor of a journal is calculated based on a three-year period. It can be viewed as an approximation of the average number of citations in a year, given to those papers in a journal that were published during the two preceding years. For example, the 2003 impact factor of a journal would be calculated as follows: A convenient way of thinking about it is that a journal that is cited once, on average, for each article published has an IF of 1 in the expression above. There are some nuances to this: ISI excludes certain article types (such as news items, correspondence, and errata) from the denominator. New journals, that are indexed from their first published issue, will receive an Impact Factor after the completion of two years' indexing; in this case, the citations to the year prior to Volume 1, and the number of articles published in the year prior to Volume 1 are known zero values. Journals that are indexed starting with a volume other than the first volume will not have an Impact Factor published until three complete data-years are known; annuals and other irregular publications, will sometimes publish no items in a particular year, affecting the count. The impact factor is for a specific time period; it is possible to calculate the impact factor for any desired period, for which the web site gives instructions. Journal Citation Reports includes a table of the relative rank of journals by Impact factor, in each specific science discipline, such as organic chemistry or psychiatry. # Debate It is sometimes useful to be able to compare different journals and research groups. For example, a sponsor of scientific research might wish to compare the results to assess the productivity of its projects. An objective measure of the importance of different publications is then required and the impact factor (or number of publications) are the only ones publicly available. However, it is important to remember that different scholarly disciplines can have very different publication and citation practices, which affect not only the number of citations, but how quickly, after publication, most articles in the subject reach their highest level of citation. In all cases, it is only relevant to consider the rank of the journal in a category of its peers, rather than the raw Impact Factor value. Impact factors are not infallible measures of journal qualitySeglen PO (1997). "Why the impact factor of journals should not be used for evaluating research". BMJ. 314 (7079): 498–502. PMID 9056804..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}. For example, it is unclear whether the number of citations a paper garners measures its actual quality or simply reflects the sheer number of publications in that particular area of research and whether there is a difference between them. Furthermore, in a journal which has long lag time between submission and publication, it might be impossible to cite articles within the three-year window. Indeed, for some journals, the time between submission and publication can be over two years, which leaves less than a year for citation. On the other hand, a longer temporal window would be slow to adjust to changes in journal impact factors. Thus, although the impact factor is appropriate for some fields of science such as molecular biology, it is not appropriate for subjects with a slower publication pattern, such as ecology. (It is possible to calculate the impact factor for any desired period, and the web site gives instructions.) Favorable properties of the impact factor include: - ISI's wide international coverage. Web of Knowledge indexes 9000 science and social science journals from 60 countries. This is perhaps only partially correct: see below. - Results are widely (though not freely) available to use and understand. - It is an objective measure. - It has a wider acceptance than any of the alternatives. - In practice, the alternative measure of quality is "prestige." This is rating by reputation, which is very slow to change, and cannot be quantified or objectively used. It merely demonstrates popularity. The most commonly mentioned faults of the impact factor include: - ISI's inadequate international coverage. Although Web of Knowledge indexes journals from 60 countries, the coverage is very uneven. Very few publications from languages other than English are included, and very few journals from the less-developed countries. Even the ones that are included are undercounted, because most of the citations to such journals will come from other journals in the same language or from the same country, most of which are not included. - The failure to include many high quality journals in the applied aspects of some subjects, such as marketing communications, public relations and promotion management and many important but not peer-reviewed technical magazines. This editorial comment of the Asian EFL Journal complains of Thomson / ISI's failure to even consider rating certain superior journals. - The failure to incorporate book publications including textbooks, handbooks and reference books into the calculations of the impact factor. - The number of citations to papers in a particular journal does not really directly measure the true quality of a journal, much less the scientific merit of the papers within it. It also reflects, at least in part, the intensity of publication or citation in that area, and the current popularity of that particular topic, along with the availability of particular journals. Journals with low circulation, regardless of the scientific merit of their contents, will never obtain high impact factors in an absolute sense, but if all the journals in a specific subject are of low circulation, as in some areas of botany and zoology, the relative standing is meaningful. Since defining the quality of an academic publication is problematic, involving non-quantifiable factors, such as the influence on the next generation of scientists, assigning this value a specific numeric measure cannot tell the whole story. - The temporal window for citation is too short, as discussed above. Classic articles are cited frequently even after several decades, but this should not affect specific journals. - In the short term - especially in the case of low-impact-factor journals - many of the citations to a certain article are made in papers written by the author(s) of the original article. This means that counting citations may be independent of the real “impact” of the work among investigators. - The absolute number of researchers, the average number of authors on each paper, and the nature of results in different research areas, as well as variations in citation habits between different disciplines, particularly the number of citations in each paper, all combine to make impact factors between different groups of scientists incommensurable. Generally, for example, medical journals have higher impact factors than mathematical journals and engineering journals. This limitation is accepted by the publishers; it has never been claimed that they are useful between fields--such a use is an indication of misunderstanding. - By merely counting the frequency of citations per article and disregarding the prestige of the citing journals, the impact factor becomes merely a metric of popularity, not of prestige. - HEFCE was urged by the Parliament of the United Kingdom Committee on Science and Technology to remind Research Assessment Exercise (RAE) panels that they are obliged to assess the quality of the content of individual articles, not the reputation of the journal in which they are published . ## Misuse of impact factor - The impact factor is often misused to predict the importance of an individual publication based on where it was published. This does not work well since a small number of publications are cited much more than the majority - for example, about 90% of Nature's 2004 impact factor was based on only a fourth of its publications. The impact factor, however, averages over all articles and thus underestimates the citations of the top cited while exaggerating the number of citations of the average publication. - Academic reviewers involved in programmatic evaluations, particularly those for doctoral degree granting institutions, often turn to ISI's proprietary IF listing of journals in determining scholarly output. This builds in a bias which automatically undervalues some types of research and distorts the total contribution each faculty member makes. - The absolute value of an impact factor is meaningless. A journal with an IF of 2 would not be very impressive in Microbiology, while it would in Oceanography. Such values are nonetheless sometimes advertised by scientific publishers. - The comparison of impact factors between different fields is invalid. Yet such comparisons have been widely used for the evaluation of not merely journals, but of scientists and of university departments. It is not possible to say, for example, that a department whose publications have an average IF below 2 is low-level. This would not make sense for Mechanical Engineering, where only two review journals attain such a value. - Outside the sciences, impact factors are relevant for fields that have a similar publication pattern to the sciences (such as economics), where research publications are almost always journal articles, that cite other journal articles. They are not relevant for literature, where the most important publications are books citing other books. Therefore, ISI does not publish a JCR for the humanities. - Even in the sciences, it is not fully relevant to fields, such as some in engineering, where the principal scientific output is conference proceedings , technical reports, and patents. - Since only the ISI database journals are used, it undercounts the number of citations from journals in less-developed countries, and less-universal languages. - Even though in practice they are applied this way, impact factors cannot correctly be the only thing to be considered by libraries in selecting journals. The local usefulness of the journal is at least equally important, as is whether or not an institution's faculty member is editor of the journal or on its editorial review board. ## Manipulation of impact factors A journal can adopt editorial policies that increase its impact factor. These editorial policies may not solely involve improving the quality of published scientific work. Journals sometimes may publish a larger percentage of review articles. While many research articles remain uncited after 3 years, nearly all review articles receive at least one citation within three years of publication, therefore review articles can raise the impact factor of the journal. The Thomson Scientific website gives directions for removing these journals from the calculation. For researchers or students having even a slight familiarity with the field, the review journals will be obvious. ## Self-citing Several methods, not necessarily with nefarious intent, exist for a journal to cite articles in the same journal which will increase the journal's impact factor. An editor of a journal may encourage authors to cite articles from that journal in the papers they submit. The degree to which this practice affects the citation count and impact factor included in the Journal Citation Reports cited journal data must therefore be examined. Most of these effects are thoroughly discussed on the site's help pages, along with ways for correcting the figures for these effects if desired. However, it is almost universal for articles in a journal to cite primarily its own articles, for those are the ones of the same merit in the same special field. If done artificially, the effect will become especially visible when (i) journals have a low impact factor (in absolute terms) and (ii) publish only few papers per year. ## Skewness An editorial in Nature stated For example, we have analysed the citations of individual papers in Nature and found that 89% of last year’s figure was generated by just 25% of our papers. The most cited Nature paper from 2002−03 was the mouse genome, published in December 2002. That paper represents the culmination of a great enterprise, but is inevitably an important point of reference rather than an expression of unusually deep mechanistic insight. So far it has received more than 1,000 citations. Within the measurement year of 2004 alone, it received 522 citations. Our next most cited paper from 2002−03 (concerning the functional organization of the yeast proteome) received 351 citations that year. Only 50 out of the roughly 1,800 citable items published in those two years received more than 100 citations in 2004. The great majority of our papers received fewer than 20 citations. This emphasizes the fact that the impact factor refers to the average number of citations per paper, and this is not a gaussian distribution. It is rather a Bradford distribution, as predicted by theory. Most papers published in a high impact factor journal will ultimately be cited many fewer times than the impact factor may seem to suggest, and some will not be cited at all. Therefore the Impact Factor of the source journal should not be used as a substitute measure of the citation impact of individual articles in the journal. Also, researchers from UCLA have estimated that when scientists write up their work and cite other people's papers, only around 20% have read the original (based on the assumption that copying a reference implies not reading the original paper). ## Use in scientific employment Though the impact factor was originally intended as an objective measure of the reputability of a journal (Garfield), it is now being increasingly applied to measure the productivity of scientists. The way it is customarily used is to examine the impact factors of the journals in which the scientist's articles have been published. This has obvious appeal for an academic administrator who knows neither the subject nor the journals. # Other measures of impact ## PageRank algorithm In 1976 Gabriel Pinski and Francis Narin suggested a recursive impact factor, to give citations from journals that have high impact greater weight than citations from low-impact journals. Such a recursive impact factor resembles the PageRank algorithm of the Google search engine, though the original Pinski and Narin paper uses a "trade balance" approach in which journals score highest when they are often cited but rarely cite other journals. A number of subsequent authors have proposed related approaches to ranking scholarly journals. In 2006, Johan Bollen, Marko A. Rodriguez, and Herbert Van de Sompel also proposed using the PageRank algorithm. From their paper: The table shows the top 10 journals by ISI Impact Factor, PageRank, and a modified system that combines the two (based on 2003 data). Nature and Science are generally regarded as the most prestigious journals, and in the combined system they come out on top. That the New England Journal of Medicine is cited even more than Nature or Science might reflect the mix of review articles and original articles that it publishes. It is necessary to analyze the data for a journal in the light of a detailed knowledge of the journal literature. The Eigenfactor is another PageRank-type measure of journal influence, with rankings freely available at eigenfactor.org.	Impact factor # Overview The Impact factor, often abbreviated IF, is a measure of the citations to science and social science journals. It is frequently used as a proxy for the importance of a journal to its field. # Overview The Impact factor was devised by Eugene Garfield, the founder of the Institute for Scientific Information, now part of Thomson, a large worldwide US-based publisher. Impact factors are calculated each year by Thomson Scientific for those journals which it indexes, and the factors and indices are published in Journal Citation Reports. Some related values, also calculated and published by the same organization, are: - the immediacy index: the number of citations the articles in a journal receive in a given year divided by the number of articles published. - the cited half-life: the median age of the articles that were cited in Journal Citation Reports each year. For example, if a journal's half-life in 2005 is 5, that means the citations from 2001-2005 are half of all the citations from that journal in 2005, and the other half of the citations precede 2001.[1] - the aggregate impact factor for a subject category: it is calculated taking into account the number of citations to all journals in the subject category and the number of articles from all the journals in the subject category. These measures apply only to journals, not individual articles or individual scientists (unlike, say, the H-index). The relative number of citations an individual article receives is better viewed as citation impact. It is, however, possible to measure the Impact factor of the journals in which a particular person has published articles. This use is widespread, but controversial. Eugene Garfield warns about the "misuse in evaluating individuals" because there is "a wide variation from article to article within a single journal".[2] Impact factors have a huge, but controversial, influence on the way published scientific research is perceived and evaluated. # Calculation The impact factor of a journal is calculated based on a three-year period. It can be viewed as an approximation of the average number of citations in a year, given to those papers in a journal that were published during the two preceding years. For example, the 2003 impact factor of a journal would be calculated as follows: A convenient way of thinking about it is that a journal that is cited once, on average, for each article published has an IF of 1 in the expression above. There are some nuances to this: ISI excludes certain article types (such as news items, correspondence, and errata) from the denominator. New journals, that are indexed from their first published issue, will receive an Impact Factor after the completion of two years' indexing; in this case, the citations to the year prior to Volume 1, and the number of articles published in the year prior to Volume 1 are known zero values. Journals that are indexed starting with a volume other than the first volume will not have an Impact Factor published until three complete data-years are known; annuals and other irregular publications, will sometimes publish no items in a particular year, affecting the count. The impact factor is for a specific time period; it is possible to calculate the impact factor for any desired period, for which the web site gives instructions. Journal Citation Reports includes a table of the relative rank of journals by Impact factor, in each specific science discipline, such as organic chemistry or psychiatry. # Debate It is sometimes useful to be able to compare different journals and research groups. For example, a sponsor of scientific research might wish to compare the results to assess the productivity of its projects. An objective measure of the importance of different publications is then required and the impact factor (or number of publications) are the only ones publicly available. However, it is important to remember that different scholarly disciplines can have very different publication and citation practices, which affect not only the number of citations, but how quickly, after publication, most articles in the subject reach their highest level of citation. In all cases, it is only relevant to consider the rank of the journal in a category of its peers, rather than the raw Impact Factor value. Impact factors are not infallible measures of journal qualitySeglen PO (1997). "Why the impact factor of journals should not be used for evaluating research". BMJ. 314 (7079): 498–502. PMID 9056804..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}. For example, it is unclear whether the number of citations a paper garners measures its actual quality or simply reflects the sheer number of publications in that particular area of research and whether there is a difference between them. Furthermore, in a journal which has long lag time between submission and publication, it might be impossible to cite articles within the three-year window. Indeed, for some journals, the time between submission and publication can be over two years, which leaves less than a year for citation. On the other hand, a longer temporal window would be slow to adjust to changes in journal impact factors. Thus, although the impact factor is appropriate for some fields of science such as molecular biology, it is not appropriate for subjects with a slower publication pattern, such as ecology. (It is possible to calculate the impact factor for any desired period, and the web site gives instructions.) Favorable properties of the impact factor include: - ISI's wide international coverage. Web of Knowledge indexes 9000 science and social science journals from 60 countries. This is perhaps only partially correct: see below. - Results are widely (though not freely) available to use and understand. - It is an objective measure. - It has a wider acceptance than any of the alternatives[citation needed]. - In practice, the alternative measure of quality is "prestige." This is rating by reputation, which is very slow to change, and cannot be quantified or objectively used. It merely demonstrates popularity. The most commonly mentioned faults of the impact factor include: - ISI's inadequate international coverage. Although Web of Knowledge indexes journals from 60 countries, the coverage is very uneven. Very few publications from languages other than English are included, and very few journals from the less-developed countries. Even the ones that are included are undercounted, because most of the citations to such journals will come from other journals in the same language or from the same country, most of which are not included. - The failure to include many high quality journals in the applied aspects of some subjects, such as marketing communications, public relations and promotion management and many important but not peer-reviewed technical magazines. This editorial comment [1] of the Asian EFL Journal complains of Thomson / ISI's failure to even consider rating certain superior journals. - The failure to incorporate book publications including textbooks, handbooks and reference books into the calculations of the impact factor. - The number of citations to papers in a particular journal does not really directly measure the true quality of a journal, much less the scientific merit of the papers within it. It also reflects, at least in part, the intensity of publication or citation in that area, and the current popularity of that particular topic, along with the availability of particular journals. Journals with low circulation, regardless of the scientific merit of their contents, will never obtain high impact factors in an absolute sense, but if all the journals in a specific subject are of low circulation, as in some areas of botany and zoology, the relative standing is meaningful. Since defining the quality of an academic publication is problematic, involving non-quantifiable factors, such as the influence on the next generation of scientists, assigning this value a specific numeric measure cannot tell the whole story. - The temporal window for citation is too short, as discussed above. Classic articles are cited frequently even after several decades, but this should not affect specific journals.[3] - In the short term - especially in the case of low-impact-factor journals - many of the citations to a certain article are made in papers written by the author(s) of the original article.[4] This means that counting citations may be independent of the real “impact” of the work among investigators. - The absolute number of researchers, the average number of authors on each paper, and the nature of results in different research areas, as well as variations in citation habits between different disciplines, particularly the number of citations in each paper, all combine to make impact factors between different groups of scientists incommensurable.[5] Generally, for example, medical journals have higher impact factors than mathematical journals and engineering journals. This limitation is accepted by the publishers; it has never been claimed that they are useful between fields--such a use is an indication of misunderstanding. - By merely counting the frequency of citations per article and disregarding the prestige of the citing journals, the impact factor becomes merely a metric of popularity, not of prestige. - HEFCE was urged by the Parliament of the United Kingdom Committee on Science and Technology to remind Research Assessment Exercise (RAE) panels that they are obliged to assess the quality of the content of individual articles, not the reputation of the journal in which they are published [2]. ## Misuse of impact factor - The impact factor is often misused to predict the importance of an individual publication based on where it was published.[6] This does not work well since a small number of publications are cited much more than the majority - for example, about 90% of Nature's 2004 impact factor was based on only a fourth of its publications.[7] The impact factor, however, averages over all articles and thus underestimates the citations of the top cited while exaggerating the number of citations of the average publication. - Academic reviewers involved in programmatic evaluations, particularly those for doctoral degree granting institutions, often turn to ISI's proprietary IF listing of journals in determining scholarly output. This builds in a bias which automatically undervalues some types of research and distorts the total contribution each faculty member makes. - The absolute value of an impact factor is meaningless. A journal with an IF of 2 would not be very impressive in Microbiology, while it would in Oceanography. Such values are nonetheless sometimes advertised by scientific publishers. - The comparison of impact factors between different fields is invalid. Yet such comparisons have been widely used for the evaluation of not merely journals, but of scientists and of university departments. It is not possible to say, for example, that a department whose publications have an average IF below 2 is low-level. This would not make sense for Mechanical Engineering, where only two review journals attain such a value. - Outside the sciences, impact factors are relevant for fields that have a similar publication pattern to the sciences (such as economics), where research publications are almost always journal articles, that cite other journal articles. They are not relevant for literature, where the most important publications are books citing other books. Therefore, ISI does not publish a JCR for the humanities. - Even in the sciences, it is not fully relevant to fields, such as some in engineering, where the principal scientific output is conference proceedings , technical reports, and patents. - Since only the ISI database journals are used, it undercounts the number of citations from journals in less-developed countries, and less-universal languages. - Even though in practice they are applied this way, impact factors cannot correctly be the only thing to be considered by libraries in selecting journals. The local usefulness of the journal is at least equally important, as is whether or not an institution's faculty member is editor of the journal or on its editorial review board. ## Manipulation of impact factors A journal can adopt editorial policies that increase its impact factor.[8] These editorial policies may not solely involve improving the quality of published scientific work. Journals sometimes may publish a larger percentage of review articles. While many research articles remain uncited after 3 years, nearly all review articles receive at least one citation within three years of publication, therefore review articles can raise the impact factor of the journal. The Thomson Scientific website gives directions for removing these journals from the calculation. For researchers or students having even a slight familiarity with the field, the review journals will be obvious. ## Self-citing Several methods, not necessarily with nefarious intent, exist for a journal to cite articles in the same journal which will increase the journal's impact factor.[5] Editorials in a journal do not count as publications. However when they cite published articles, often articles from the same journal, those citations increase the citation count for the article. This effect is hard to evaluate, for the distinction between editorial comment and short original articles is not obvious. "Letters to the editor" might refer to either class. An editor of a journal may encourage authors to cite articles from that journal in the papers they submit. The degree to which this practice affects the citation count and impact factor included in the Journal Citation Reports cited journal data must therefore be examined. Most of these effects are thoroughly discussed on the site's help pages, along with ways for correcting the figures for these effects if desired. However, it is almost universal for articles in a journal to cite primarily its own articles, for those are the ones of the same merit in the same special field. If done artificially, the effect will become especially visible when (i) journals have a low impact factor (in absolute terms) and (ii) publish only few papers per year. ## Skewness An editorial in Nature stated[7] For example, we have analysed the citations of individual papers in Nature and found that 89% of last year’s figure was generated by just 25% of our papers. The most cited Nature paper from 2002−03 was the mouse genome, published in December 2002. That paper represents the culmination of a great enterprise, but is inevitably an important point of reference rather than an expression of unusually deep mechanistic insight. So far it has received more than 1,000 citations. Within the measurement year of 2004 alone, it received 522 citations. Our next most cited paper from 2002−03 (concerning the functional organization of the yeast proteome) received 351 citations that year. Only 50 out of the roughly 1,800 citable items published in those two years received more than 100 citations in 2004. The great majority of our papers received fewer than 20 citations. This emphasizes the fact that the impact factor refers to the average number of citations per paper, and this is not a gaussian distribution. It is rather a Bradford distribution, as predicted by theory. Most papers published in a high impact factor journal will ultimately be cited many fewer times than the impact factor may seem to suggest, and some will not be cited at all. Therefore the Impact Factor of the source journal should not be used as a substitute measure of the citation impact of individual articles in the journal. Also, researchers from UCLA have estimated that when scientists write up their work and cite other people's papers, only around 20% have read the original (based on the assumption that copying a reference implies not reading the original paper).[9] ## Use in scientific employment Though the impact factor was originally intended as an objective measure of the reputability of a journal (Garfield), it is now being increasingly applied to measure the productivity of scientists. The way it is customarily used is to examine the impact factors of the journals in which the scientist's articles have been published. This has obvious appeal for an academic administrator who knows neither the subject nor the journals. # Other measures of impact ## PageRank algorithm In 1976 Gabriel Pinski and Francis Narin suggested a recursive impact factor, to give citations from journals that have high impact greater weight than citations from low-impact journals.[10] Such a recursive impact factor resembles the PageRank algorithm of the Google search engine, though the original Pinski and Narin paper uses a "trade balance" approach in which journals score highest when they are often cited but rarely cite other journals. A number of subsequent authors have proposed related approaches to ranking scholarly journals.[11][12][13] In 2006, Johan Bollen, Marko A. Rodriguez, and Herbert Van de Sompel also proposed using the PageRank algorithm.[14] From their paper: The table shows the top 10 journals by ISI Impact Factor, PageRank, and a modified system that combines the two (based on 2003 data). Nature and Science are generally regarded as the most prestigious journals, and in the combined system they come out on top. That the New England Journal of Medicine is cited even more than Nature or Science might reflect the mix of review articles and original articles that it publishes. It is necessary to analyze the data for a journal in the light of a detailed knowledge of the journal literature. The Eigenfactor is another PageRank-type measure of journal influence,[15] with rankings freely available at eigenfactor.org.	https://www.wikidoc.org/index.php/Impact_factor
df2b73095960850b35b5fa2bb5514591b30b0889	wikidoc	Incidentalome	Incidentalome # Overview The incidentalome is the phenomenon of all possible incidental findings.The term was coined as an extension of incidentaloma which refers to the incidental, often radiographic findings of masses or tumors whose significance and prognosis is therefore poorly understood. In the genomic era, the lack of prior probabilities regarding the clinical import of each genetic variant creates the likelihood of a large proportion of false positives, if genetic testing is not placed on a systematic quantitative basis. "If practitioners pursue unexpected genomic findings without thought, there may be untoward consequences. Specifically, physicians will be overwhelmed by the complexity of pursuing unexpected genomic measurements, patients will be subject to unnecessary follow-up tests, causing additional morbidity, and the cost of genomic medicine will increase substantially with little benefit to patients or physicians, thus casting into question the benefit of genomic-based medicine." The incidentalome raises a challenge for both the FDA approval of panels (e.g. SNP chips) of genetic tests as well as the substance of medical education in the genomic era.	Incidentalome # Overview The incidentalome is the phenomenon of all possible incidental findings.The term was coined as an extension of incidentaloma which refers to the incidental, often radiographic findings of masses or tumors whose significance and prognosis is therefore poorly understood. In the genomic era, the lack of prior probabilities regarding the clinical import of each genetic variant creates the likelihood of a large proportion of false positives, if genetic testing is not placed on a systematic quantitative basis. "If practitioners pursue unexpected genomic findings without thought, there may be untoward consequences. Specifically, physicians will be overwhelmed by the complexity of pursuing unexpected genomic measurements, patients will be subject to unnecessary follow-up tests, causing additional morbidity, and the cost of genomic medicine will increase substantially with little benefit to patients or physicians, thus casting into question the benefit of genomic-based medicine." [1] The incidentalome raises a challenge for both the FDA approval of panels (e.g. SNP chips) [2] of genetic tests as well as the substance of medical education in the genomic era. - ↑ http://www.google.com/url?sa=t&ct=res&cd=1&url=http%3A%2F%2Faspe.hhs.gov%2FPHC%2FRFI%2Fcomments%2F53-1.pdf&ei=6YQGRpyIM4iKgASf1sz_Aw&usg=__MArFWEc5qe04AlZhY8jOZAZUGdA=&sig2=zUYFaluLULUHwhpwLRCqmQ - ↑ http://www.thepersonalgenome.com/2006/07/the_incidentalo.html Template:WikiDoc Sources	https://www.wikidoc.org/index.php/Incidentalome
23b3fdc23d6ad0069f4247132c25c82c65cf9d51	wikidoc	Indiana pouch	Indiana pouch Steven C. Campbell, M.D., Ph.D. # Overview An Indiana pouch is a surgically-created urinary diversion used to create a way for the body to store and eliminate urine for patients who have had their urinary bladders removed as a result of bladder cancer,, or who are not continent due to a congenital, neurogenic bladder. With this type of surgery, a reservoir, or pouch, is created out of approximately two feet of the ascending colon and a portiom of the ileum (a part of the small intestine). The ureters are surgically removed from the bladder and repositioned to drain into the pouch. A piece of small intestine is brought out through a small opening in the abdominal wall called a stoma. Since a segment including the large and small intestines are utilized, also included is the ileal-ceceal valve. This is a one-way valve located between the small and large intestines which normally prevents the passage of bacteria and digested matter from re-entering the small intestine. Originally, it was thought that removing the ileal-ceceal valve from the digestive tract would result in diarrhea, but this has not shown to be the case. After a period of several weeks, the body adjusts to the absence of this valve by absorbing more liquids and nutrients. Patients can usually expect a hospital stay between seven and ten days for this surgery. The abdominal incision (vertical) may be up to approximately eight inches long and is typically closed with staples on the outside and several layers of dissolvable stitches on the inside. After surgery, patients will have a three drainage tubes place while tissues heal: one through the newly-created stoma, one through another temporary opening in the abdominal wall into the pouch, and an SP tube. In the hospital, the SP tube and external staples will be removed after several days. The remaining tubes will be connected to collection bags which will be worn on each leg. After sufficient healing, the tube will be removed from the stoma and the patient will begin to catheterize the pouch every two hours. Since one other tube will still be in place, patients can sleep through the night since the collection bag can be attached to that tube at night time. After approximately one month, patients will return to the hospital for an x-ray where dye will be instilled into the pouch to verify that there is no leakage. If there is no leakage, this last tube will be removed. Emptying time now may be increased to 3 hours, however, now the patient will need to wake up during the night to empty the pouch. Over time, emptying time can increased up to 4-6 hours. The pouch reaches its final size at approximately six months, and will then hold up to 1,200 cubic centimeters (cc's). Each day, the pouch will need to be irrigated with 60 cc's of sterile water. This removes mucus, salts, and bacteria. If consumption of liquids is reduced in the evening, patients should be able to sleep through the night after approximately six months. In contrast to other urinary diversion techniques like the ileal conduit, the Indiana pouch has the advantage of not using an external pouch adhered to the abdomen to store urine. This can result in a better body image. Also, there will not be the worry of an external appliance coming loose and leaking. Additionally, the cost of urostomy appliances can be significant, and is usually not covered in full by most health insurance. Indiana pouch surgery can be done in young patients as long as they have the ability to empty the pouch on a schedule. Indiana pouch surgery also has been done in patients up into their 70's. Some patients, after having a ileal conduit, which is incontinent and requires an appliance, have opted to have the Indiana pouch as elective surgery, if they are a candidate. It has been documented that the Indiana pouch may reduce the possibility of kidney damage since the ureters are repositioned lower in the abdomin and this reduces the possible back-flow to the kidneys. After having the surgery, patients must wear a medical alert bracelet indicating they have an Indiana pouch.	Indiana pouch Template:Search infobox Steven C. Campbell, M.D., Ph.D. # Overview An Indiana pouch is a surgically-created urinary diversion used to create a way for the body to store and eliminate urine for patients who have had their urinary bladders removed as a result of bladder cancer,[[pelvic exenteration], or who are not continent due to a congenital, neurogenic bladder. With this type of surgery, a reservoir, or pouch, is created out of approximately two feet of the ascending colon and a portiom of the ileum (a part of the small intestine). The ureters are surgically removed from the bladder and repositioned to drain into the pouch. A piece of small intestine is brought out through a small opening in the abdominal wall called a stoma. Since a segment including the large and small intestines are utilized, also included is the ileal-ceceal valve. This is a one-way valve located between the small and large intestines which normally prevents the passage of bacteria and digested matter from re-entering the small intestine. Originally, it was thought that removing the ileal-ceceal valve from the digestive tract would result in diarrhea, but this has not shown to be the case. After a period of several weeks, the body adjusts to the absence of this valve by absorbing more liquids and nutrients. Patients can usually expect a hospital stay between seven and ten days for this surgery. The abdominal incision (vertical) may be up to approximately eight inches long and is typically closed with staples on the outside and several layers of dissolvable stitches on the inside. After surgery, patients will have a three drainage tubes place while tissues heal: one through the newly-created stoma, one through another temporary opening in the abdominal wall into the pouch, and an SP tube. In the hospital, the SP tube and external staples will be removed after several days. The remaining tubes will be connected to collection bags which will be worn on each leg. After sufficient healing, the tube will be removed from the stoma and the patient will begin to catheterize the pouch every two hours. Since one other tube will still be in place, patients can sleep through the night since the collection bag can be attached to that tube at night time. After approximately one month, patients will return to the hospital for an x-ray where dye will be instilled into the pouch to verify that there is no leakage. If there is no leakage, this last tube will be removed. Emptying time now may be increased to 3 hours, however, now the patient will need to wake up during the night to empty the pouch. Over time, emptying time can increased up to 4-6 hours. The pouch reaches its final size at approximately six months, and will then hold up to 1,200 cubic centimeters (cc's). Each day, the pouch will need to be irrigated with 60 cc's of sterile water. This removes mucus, salts, and bacteria. If consumption of liquids is reduced in the evening, patients should be able to sleep through the night after approximately six months. In contrast to other urinary diversion techniques like the ileal conduit, the Indiana pouch has the advantage of not using an external pouch adhered to the abdomen to store urine. This can result in a better body image. Also, there will not be the worry of an external appliance coming loose and leaking. Additionally, the cost of urostomy appliances can be significant, and is usually not covered in full by most health insurance. Indiana pouch surgery can be done in young patients as long as they have the ability to empty the pouch on a schedule. Indiana pouch surgery also has been done in patients up into their 70's. Some patients, after having a ileal conduit, which is incontinent and requires an appliance, have opted to have the Indiana pouch as elective surgery, if they are a candidate. It has been documented that the Indiana pouch may reduce the possibility of kidney damage since the ureters are repositioned lower in the abdomin and this reduces the possible back-flow to the kidneys. After having the surgery, patients must wear a medical alert bracelet indicating they have an Indiana pouch. Template:WH Template:WikiDoc Sources	https://www.wikidoc.org/index.php/Indiana_pouch
931002c96a67b9bd9dcd694274f6159f5c782b93	wikidoc	West syndrome	West syndrome Synonyms and keywords: Infantile spasms; infantile epileptic encephalopathy; jackknife convulsions; massive myoclonus; salaam spasms # Overview West syndrome, is an uncommon to rare and serious form of epilepsy in infants. The triad of developmental regression, infantile spasmsand pattern of hypsarrhythmia on EEG is termed as west syndrome. The syndrome is age-related, generally occurring between the third and the twelfth month, generally manifesting around the fifth month. There are various causes ("polyetiology"). The syndrome is often caused by an organic brain dysfunction whose origins may be prenatal, perinatal (caused during birth) or postnatal. # Historical Perspecitve West syndrome was named after the English doctor and surgeon William James West (1793-1848), who lived in Tonbridge. In 1841 he observed this type of epilepsy in his own son, who was approximately four months old at the time. He published his observations from a scientific perspective in an article in The Lancet. He named the seizures "Salaam Tics" at the time. # Pathophysiology It is still unknown which bio-chemical mechanisms lead to the occurrence of West syndrome. It is conjectured that it is a malfunction of the neurotransmitter function, or more precisely, a malfunction in the regulation of the GABA transmission process. Another possibility being researched is a hyper-production of the Corticotropin-releasing hormone (CRH). It is possible that more than one factor is involved. Both hypotheses are supported by the effect of certain medications used to treat West syndrome. ## Causes If a cause presents itself, the syndrome is referred to as symptomatic West syndrome, as the attacks manifest as a symptom of another anomaly. These are the possible causes being considered: - In around one third of the children, there is evidence of a profound organic disorder of the brain. This includes: Microcephaly Cortical dysplasia Cerebral atrophy Lissencephaly Bacterial meningitis Phakomatosis (e.g. bourneville's disease) Aicardi syndrome Tuberous sclerosis Cephalhematoma and Vascular malformation. - Microcephaly - Cortical dysplasia - Cerebral atrophy - Lissencephaly - Bacterial meningitis - Phakomatosis (e.g. bourneville's disease) - Aicardi syndrome - Tuberous sclerosis - Cephalhematoma and - Vascular malformation. - Furthermore, other causes increasingly being named in the literature are: Incontinentia pigmenti Foix-Chavany-Marie syndrome Patau syndrome (trisomy 13) Sturge-Weber syndrome Neurometabolic diseases Congential infections (e.g. Cytomegalovirus) Hypoglycemia Brain damage due to asphyxiation or hypoxia (lack of oxygen, e.g. during birth), periventricular leukomalacia, cephalhematoma, cerebrovascular accident or brain damage of various types as well as that caused by premature birth. - Incontinentia pigmenti - Foix-Chavany-Marie syndrome - Patau syndrome (trisomy 13) - Sturge-Weber syndrome - Neurometabolic diseases - Congential infections (e.g. Cytomegalovirus) - Hypoglycemia - Brain damage due to asphyxiation or hypoxia (lack of oxygen, e.g. during birth), periventricular leukomalacia, cephalhematoma, cerebrovascular accident or brain damage of various types as well as that caused by premature birth. - There are known cases in which the spasms occurred for the first time after vaccination against Measles, Mumps and Rubella or Tetanus, Pertussis, Diphtheria, Polio, Hepatitis B and Haemophilus influenzae Type B. However, stress of any kind is a common trigger for seizures, and the immunization occurs during the time-frame in which many typical cases become conspicuous. There is no causal relationship between immunization and West syndrome, since in many cases West syndrome is not recognized as iatrogenic. ### West syndrome in Down syndrome babies On average, West syndrome appears in 1 to 5 per 100 children with Down's syndrome as babies. Whereas this form of epilepsy is relatively difficult to treat in children who do not have the chromosomal differences involved in Down's syndrome, the syndrome often affects those who do far more mildly and they often react better to medication. The German Down Syndrom InfoCenter noted in 2003 that what was normally a serious epilepsy was in such cases often a relatively benign one. EEG records for Down's syndrome children are often more symmetrical with fewer unusual findings. Although not all children can become entirely free from attacks with medication, children with Down's syndrome are less likely to go on to develop Lennox-Gastaut syndrome or other forms of epilepsy than those without additional hereditary material on the 21st chromosome. The reason why it is easier to treat children with Down's syndrome is not known. ## Cryptogenic When a direct cause cannot be determined but the children has other neurological disorder, the case is referred to as cryptogenic West syndrome, where an underlying cause is most likely but even with our modern means cannot be detected. Sometimes multiple children within the same family develop West syndrome. In this case it is also referred to as cryptogenic, in which genetic and sometimes hereditary influences play a role. There are known cases in which West syndrome appears in successive generations in boys; this has to do with X-chromosomal heredity. ## Idiopathic Occasionally the syndrome is referred to as idiopathic West syndrome, when a cause cannot be determined. Important diagnostic criteria are: - Regular development until the onset of the attacks or before the beginning of the therapy - no pathological findings in neurological or neuroradiological studies - no evidence of a trigger for the spasms Those are becoming rare due to modern medicine. # Epidemiology and Demography Prevalence is around 1:4000 to 1:6000. ## Age In 45 out of every 50 children affected, the spasms appear for the first time between the third and the twelfth month of age. In rarer cases, spasms may occur in the first two months or during the second to fourth year of age. ## Gender Statistically, boys are more likely to be affected than girls at a ratio of around 3:2. # Natural History, Complications and Prognosis ## Complications - Cognitive disabilities - Learning difficulties - Behavioural problems - Cerebral palsy (up to 5 out of 10 children) - Psychological disorders - Autism ## Prognosis It is not possible to make a generalised prognosis for development due to the variability of causes, as mentioned above, the differing types of symptoms and etiology. Each case must be considered individually. The prognosis for children with idiopathic West syndrome are mostly more positive than for those with the cryptogenic or symptomatic forms. Idiopathic cases are less likely to show signs of developmental problems before the attacks begin, the attacks can often be treated more easily and effectively and there is a lower relapse rate. Children with this form of the syndrome are less likely to go on to develop other forms of epilepsy; around two in every five children develop at the same rate as healthy children. In other cases, however, treatment of West syndrome is relatively difficult and the results of therapy often dissatisfying; for children with symptomatic and cryptogenic West syndrome, the prognosis is generally not positive, especially when they prove resistant to therapy. Statistically, 5 out of every 100 children with West syndrome do not survive beyond five years of age, in some cases due to the cause of the syndrome, in others for reasons related to their medication. Only less than half of all children can become entirely free from attacks with the help of medication. Statistics show that treatment produces a satisfactory result in around three out of ten cases, with only one in every 25 children's cognitive and motoric development developing more or less normally. A large proportion (up to 90%) of children suffer severe physical and cognitive impairments, even when treatment for the attacks is successful. This is not usually because of the epileptic fits, but rather because of the causes behind them (cerebral anomalies or their location or degree of severity). Severe, frequent attacks can (further) damage the brain. As many as 6 out of 10 children with West syndrome suffer from epilepsy later in life. Sometimes West syndrome turns into a focal or other generalised epilepsy. Around half of all children develop Lennox-Gastaut syndrome. # Diagnosis Infantile spasms are often misdiagnosed as colic. The most useful test in diagnosing seizures is EEG. MRI and Ct scans can be done to rule out oragnic causes of west syndrome. Hypsarrhythmia, the pathognomonic EEG pattern of West Syndrome is typically characterized by a high amplitude, arrhythmic and asynchronous pattern. Children with infantile spasms and hypsarrhythmic EEGs had marked abnormalities in coherence and spectral power as compared to normal children. The epileptic seizures which can be observed in infants with West syndrome fall into three categories. Typically, the following triad of attack types appears; while the three types usually appear simultaneously, they also can occur independently of each other: - Lightning attacks: Sudden, severe myoclonic convulsions of the entire body or several parts of the body in split seconds, and the legs in particular are bent (flexor muscle convulsions here are generally more severe than extensor ones). - Nodding attacks: Convulsions of the throat and neck flexor muscles, during which the chin is fitfully jerked towards the breast or the head is drawn inward. - Salaam or jackknife attacks: a flexor spasm with rapid bending of the head and torso forward and simultaneous raising and bending of the arms while partially drawing the hands together in front of the chest and/or flailing. If one imagined this act in slow motion, it would appear similar to the oriental ceremonial greeting (Salaam), from which this type of attack derives its name. # Treatment Compared with other forms of epilepsy, West syndrome is difficult to treat. To raise the chance of successful treatment and keep down the risk of longer-lasting effects, it is very important that the condition is diagnosed as early as possible and that treatment begins straight away. However, there is no guarantee that therapy will work even in this case. Insufficient research has yet been carried out into whether the form of treatment has an effect upon the long-term prognosis. Based on what is known today, the prognosis depends mainly on the cause of the attacks and the length of time that hypsarrhythmia lasts. In general it can be said that the prognosis is worse when the patient does not react as well to therapy and the epileptic over-activity in the brain continues. Treatment differs in each individual case and depends on the cause of the West syndrome (etiological classification) and the state of brain development at the time of the damage. Due to their side-effects, two drugs are currently being used as the first-line treatment. - ACTH - Use primarily in United States Side effects are: Weight gain, especially in the trunk and face, hypertension, metabolic abnormalities, severe irritability, osteoporosis, sepsis, and congestive heart failure. - Side effects are: Weight gain, especially in the trunk and face, hypertension, metabolic abnormalities, severe irritability, osteoporosis, sepsis, and congestive heart failure. - Vigabatrin (Sabril) - Approved in several countries, like most Europe, Canada and Mexico. Side effects are: Somnolence, headache, dizziness, fatigue, weight gain, decreased vision or other vision changes - Side effects are: Somnolence, headache, dizziness, fatigue, weight gain, decreased vision or other vision changes Vigabatrin is known for being effective, especially in children with tuberous sclerosis, with few and benign side effects. But due to some recent studies showing visual field constriction (loss of peripheral vision), it is not yet approved in United States. It is currently debated that a short use (6 months or less) of Vigabatrin will not affect vision. Also, considering the effect of frequent seizures on day to day life and mental development, some parents prefer to take the risk of some vision loss. When those two are proving ineffective, other drugs may be used in conjunction or alone. topiramate (Topamax), lamotrigine (Lamictal), levetiracetam (Keppra) and zonisamide (Zonegran) are amongst the most widely use. The ketogenic diet have been tested and his shown to be effective, up to 70% of children having a 50% or more reduction in seizure.	West syndrome Template:DiseaseDisorder infobox Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Synonyms and keywords: Infantile spasms; infantile epileptic encephalopathy; jackknife convulsions; massive myoclonus; salaam spasms # Overview West syndrome, is an uncommon to rare and serious form of epilepsy in infants. The triad of developmental regression, infantile spasms[1]and pattern of hypsarrhythmia on EEG is termed as west syndrome. The syndrome is age-related, generally occurring between the third and the twelfth month, generally manifesting around the fifth month. There are various causes ("polyetiology"). The syndrome is often caused by an organic brain dysfunction whose origins may be prenatal, perinatal (caused during birth) or postnatal. # Historical Perspecitve West syndrome was named after the English doctor and surgeon William James West (1793-1848), who lived in Tonbridge. In 1841 he observed this type of epilepsy in his own son, who was approximately four months old at the time. He published his observations from a scientific perspective in an article in The Lancet. He named the seizures "Salaam Tics" at the time. # Pathophysiology It is still unknown which bio-chemical mechanisms lead to the occurrence of West syndrome. It is conjectured that it is a malfunction of the neurotransmitter function, or more precisely, a malfunction in the regulation of the GABA transmission process. Another possibility being researched is a hyper-production of the Corticotropin-releasing hormone (CRH). It is possible that more than one factor is involved. Both hypotheses are supported by the effect of certain medications used to treat West syndrome. ## Causes If a cause presents itself, the syndrome is referred to as symptomatic West syndrome, as the attacks manifest as a symptom of another anomaly. These are the possible causes being considered: - In around one third of the children, there is evidence of a profound organic disorder of the brain. This includes: Microcephaly Cortical dysplasia Cerebral atrophy Lissencephaly Bacterial meningitis Phakomatosis (e.g. bourneville's disease) Aicardi syndrome Tuberous sclerosis Cephalhematoma and Vascular malformation. - Microcephaly - Cortical dysplasia - Cerebral atrophy - Lissencephaly - Bacterial meningitis - Phakomatosis (e.g. bourneville's disease) - Aicardi syndrome - Tuberous sclerosis - Cephalhematoma and - Vascular malformation. - Furthermore, other causes increasingly being named in the literature are: Incontinentia pigmenti Foix-Chavany-Marie syndrome Patau syndrome (trisomy 13) Sturge-Weber syndrome Neurometabolic diseases Congential infections (e.g. Cytomegalovirus) Hypoglycemia Brain damage due to asphyxiation or hypoxia (lack of oxygen, e.g. during birth), periventricular leukomalacia, cephalhematoma, cerebrovascular accident or brain damage of various types as well as that caused by premature birth. - Incontinentia pigmenti - Foix-Chavany-Marie syndrome - Patau syndrome (trisomy 13) - Sturge-Weber syndrome - Neurometabolic diseases - Congential infections (e.g. Cytomegalovirus) - Hypoglycemia - Brain damage due to asphyxiation or hypoxia (lack of oxygen, e.g. during birth), periventricular leukomalacia, cephalhematoma, cerebrovascular accident or brain damage of various types as well as that caused by premature birth. - There are known cases in which the spasms occurred for the first time after vaccination against Measles, Mumps and Rubella or Tetanus, Pertussis, Diphtheria, Polio, Hepatitis B and Haemophilus influenzae Type B. However, stress of any kind is a common trigger for seizures, and the immunization occurs during the time-frame in which many typical cases become conspicuous. There is no causal relationship between immunization and West syndrome, since in many cases West syndrome is not recognized as iatrogenic. ### West syndrome in Down syndrome babies On average, West syndrome appears in 1 to 5 per 100 children with Down's syndrome as babies. Whereas this form of epilepsy is relatively difficult to treat in children who do not have the chromosomal differences involved in Down's syndrome, the syndrome often affects those who do far more mildly and they often react better to medication. The German Down Syndrom InfoCenter noted in 2003 that what was normally a serious epilepsy was in such cases often a relatively benign one. EEG records for Down's syndrome children are often more symmetrical with fewer unusual findings. Although not all children can become entirely free from attacks with medication, children with Down's syndrome are less likely to go on to develop Lennox-Gastaut syndrome or other forms of epilepsy than those without additional hereditary material on the 21st chromosome. The reason why it is easier to treat children with Down's syndrome is not known. ## Cryptogenic When a direct cause cannot be determined but the children has other neurological disorder, the case is referred to as cryptogenic West syndrome, where an underlying cause is most likely but even with our modern means cannot be detected. Sometimes multiple children within the same family develop West syndrome. In this case it is also referred to as cryptogenic, in which genetic and sometimes hereditary influences play a role. There are known cases in which West syndrome appears in successive generations in boys; this has to do with X-chromosomal heredity. ## Idiopathic Occasionally the syndrome is referred to as idiopathic West syndrome, when a cause cannot be determined. Important diagnostic criteria are: - Regular development until the onset of the attacks or before the beginning of the therapy - no pathological findings in neurological or neuroradiological studies - no evidence of a trigger for the spasms Those are becoming rare due to modern medicine. # Epidemiology and Demography Prevalence is around 1:4000 to 1:6000. ## Age In 45 out of every 50 children affected, the spasms appear for the first time between the third and the twelfth month of age. In rarer cases, spasms may occur in the first two months or during the second to fourth year of age. ## Gender Statistically, boys are more likely to be affected than girls at a ratio of around 3:2. # Natural History, Complications and Prognosis ## Complications - Cognitive disabilities - Learning difficulties - Behavioural problems - Cerebral palsy (up to 5 out of 10 children) - Psychological disorders - Autism ## Prognosis It is not possible to make a generalised prognosis for development due to the variability of causes, as mentioned above, the differing types of symptoms and etiology. Each case must be considered individually. The prognosis for children with idiopathic West syndrome are mostly more positive than for those with the cryptogenic or symptomatic forms. Idiopathic cases are less likely to show signs of developmental problems before the attacks begin, the attacks can often be treated more easily and effectively and there is a lower relapse rate. Children with this form of the syndrome are less likely to go on to develop other forms of epilepsy; around two in every five children develop at the same rate as healthy children. In other cases, however, treatment of West syndrome is relatively difficult and the results of therapy often dissatisfying; for children with symptomatic and cryptogenic West syndrome, the prognosis is generally not positive, especially when they prove resistant to therapy. Statistically, 5 out of every 100 children with West syndrome do not survive beyond five years of age, in some cases due to the cause of the syndrome, in others for reasons related to their medication. Only less than half of all children can become entirely free from attacks with the help of medication. Statistics show that treatment produces a satisfactory result in around three out of ten cases, with only one in every 25 children's cognitive and motoric development developing more or less normally. A large proportion (up to 90%) of children suffer severe physical and cognitive impairments, even when treatment for the attacks is successful. This is not usually because of the epileptic fits, but rather because of the causes behind them (cerebral anomalies or their location or degree of severity). Severe, frequent attacks can (further) damage the brain. As many as 6 out of 10 children with West syndrome suffer from epilepsy later in life. Sometimes West syndrome turns into a focal or other generalised epilepsy. Around half of all children develop Lennox-Gastaut syndrome. # Diagnosis Infantile spasms are often misdiagnosed as colic. The most useful test in diagnosing seizures is EEG. MRI and Ct scans can be done to rule out oragnic causes of west syndrome. Hypsarrhythmia, the pathognomonic EEG pattern of West Syndrome is typically characterized by a high amplitude, arrhythmic and asynchronous pattern. Children with infantile spasms and hypsarrhythmic EEGs had marked abnormalities in coherence and spectral power as compared to normal children.[2] The epileptic seizures which can be observed in infants with West syndrome fall into three categories. Typically, the following triad of attack types appears; while the three types usually appear simultaneously, they also can occur independently of each other: - Lightning attacks: Sudden, severe myoclonic convulsions of the entire body or several parts of the body in split seconds, and the legs in particular are bent (flexor muscle convulsions here are generally more severe than extensor ones). - Nodding attacks: Convulsions of the throat and neck flexor muscles, during which the chin is fitfully jerked towards the breast or the head is drawn inward. - Salaam or jackknife attacks: a flexor spasm with rapid bending of the head and torso forward and simultaneous raising and bending of the arms while partially drawing the hands together in front of the chest and/or flailing. If one imagined this act in slow motion, it would appear similar to the oriental ceremonial greeting (Salaam), from which this type of attack derives its name. \ # Treatment Compared with other forms of epilepsy, West syndrome is difficult to treat. To raise the chance of successful treatment and keep down the risk of longer-lasting effects, it is very important that the condition is diagnosed as early as possible and that treatment begins straight away. However, there is no guarantee that therapy will work even in this case. Insufficient research has yet been carried out into whether the form of treatment has an effect upon the long-term prognosis. Based on what is known today, the prognosis depends mainly on the cause of the attacks and the length of time that hypsarrhythmia lasts. In general it can be said that the prognosis is worse when the patient does not react as well to therapy and the epileptic over-activity in the brain continues. Treatment differs in each individual case and depends on the cause of the West syndrome (etiological classification) and the state of brain development at the time of the damage. Due to their side-effects, two drugs are currently being used as the first-line treatment. - ACTH - Use primarily in United States Side effects are: Weight gain, especially in the trunk and face, hypertension, metabolic abnormalities, severe irritability, osteoporosis, sepsis, and congestive heart failure. - Side effects are: Weight gain, especially in the trunk and face, hypertension, metabolic abnormalities, severe irritability, osteoporosis, sepsis, and congestive heart failure. - Vigabatrin (Sabril) - Approved in several countries, like most Europe, Canada and Mexico. Side effects are: Somnolence, headache, dizziness, fatigue, weight gain, decreased vision or other vision changes - Side effects are: Somnolence, headache, dizziness, fatigue, weight gain, decreased vision or other vision changes Vigabatrin is known for being effective, especially in children with tuberous sclerosis, with few and benign side effects. But due to some recent studies[3] showing visual field constriction (loss of peripheral vision), it is not yet approved in United States. It is currently debated that a short use (6 months or less) of Vigabatrin will not affect vision. Also, considering the effect of frequent seizures on day to day life and mental development, some parents prefer to take the risk of some vision loss. When those two are proving ineffective, other drugs may be used in conjunction or alone. topiramate (Topamax), lamotrigine (Lamictal), levetiracetam (Keppra) and zonisamide (Zonegran) are amongst the most widely use. The ketogenic diet have been tested and his shown to be effective[4], up to 70% of children having a 50% or more reduction in seizure[5].	https://www.wikidoc.org/index.php/Infantile_spasm
657d03f6b31b4e23a45436f42b061d4c6656f3ca	wikidoc	Intercystitis	Intercystitis Interstitial cystitis is chronic inflammation of the wall of the urinary bladder. Inflammation can lead to scarring, pinpoint bleeding of the bladder wall, and a decreased bladder capacity. # Causes Because bacteria, fungi or viruses are rarely found in the urine of people with interstitial cystitis, the cause is unclear. Possible causes include: - An autoimmune response that occurs following a bacterial infection of the bladder - Bacteria that cling too tightly to the wall of the bladder to be detected in the urine - A "leaky" inner lining of the bladder that allows irritating substances in the urine to come into contact with the bladder wall # Risk Factors - Sex: female - History of childhood bladder problems # Symptoms The symptoms of interstitial cystitis vary from person to person. They can also occur in cycles. Some people experience periods of intense symptoms followed by periods of remission. Pain can be severe enough to keep people from working or even walking. Symptoms can include: - Discomfort, pain, or pressure in the bladder or pelvic area - Frequent need to urinate (up to 60 times per day in severe cases) - Urgent need to urinate - Pain during intercourse - Blood and pus in the urine - Shrunken bladder # Diagnosis A doctor will ask about your symptoms and medical history, and perform a physical exam. In addition, your urine will be tested for pus and bacteria. If bacteria are present in the urine, you will likely be diagnosed with acute cystitis—a typical bladder infection. If no bacteria are present, your doctor will likely do other tests. A diagnosis of interstitial cystitis will only be made after other conditions have been ruled out and a cystoscopy with bladder distention has been done. This consists of distending (stretching) the bladder to its full capacity by instilling gas or liquids through the cystoscope. A cystoscopy will help your doctor see if there is scarring, bleeding, or inflammation on the bladder wall. # Treatment There is no treatment to cure interstitial cystitis. Treatment is aimed at relieving symptoms. You may have to try several different treatments before you experience relief. Treatments include: ### Bladder Distention Some people experience relief after the bladder distention—done during the cystoscopy—is done. ### Bladder Instillation During bladder instillation, a "wash" is put into the bladder through a tube in the urethra. It is held for anywhere from a few seconds to 15 minutes and then voided. There are several different types of solutions used. Some coat the bladder and are thought to decrease the inflammation. ### Medication Medications may include: - Bladder coating - taken orally, they can coat and protect the bladder - Antidepressants and pain relievers - for pain relief - Antihistamines - may help stop the cycle of inflammation - Antispasmodics - may alleviate frequency and urgency of urination ### Diet Many people find that changes in diet can help relieve pain. Finally, in the Summer of 2006, researchers Barbara Shorter RD and Robert Moldwin MD provided concrete proof that diet does exacerbate IC symptoms when they released the preliminary data for the first formal research study on diet and IC in a lecture on the Interstitial Cystitis Network. Foods commonly reported to aggravate interstitial cystitis include: - Coffees (Regular & Decaf) - Teas (Regular, Green & Blended Herbals) - Chocolate - Artificial sweeteners - Alcohol - Acidic foods - Carbonated beverages ### Transcutaneous Electrical Nerve Stimulation (TENS) A Transcutaneous Electrical Nerve Stimulator, or TENS, is an external device that sends mild electrical impulses into the body. It has been helpful in relieving pain and decreasing frequency of urination in some people. ### Bladder Training Some people are able to train the bladder to have better control by setting a regular timed schedule for emptying their bladder. The amount of time between voidings is gradually increased. Bladder training should be attempted only after pain relief has been accomplished. ### Surgery Surgery is a treatment of last resort. It is used after all other treatment methods have been exhausted and if the pain is severe. Many people continue to have pain even after surgery. # Prevention There are no guidelines for preventing interstitial cystitis because the cause is unknown. # Organizations - Interstitial Cystitis Association - Interstitial Cystitis Network - ICU Texas - The Cystitis and Overactive Bladder Foundation - The Interstitial Cystitis Association # Resources - IC Patient Handbook In addition to traditional IC therapies, diet modification remains a core self help strategy as foods that are irritating to the bladder dramatically worsen the symptoms that patients may experience. Foods high in acid and/or caffeine (such as all coffees, regular teas, green teas, sodas, diet sodas, artificial sugars and most fruit juices) should be avoided. The daily goal of patients should be to soothe rather than irritate the bladder wall. - The Top Five List of Forbidden Foods - IC Survival Guide by Robert Moldwin, MD - A Taste of the Good Life: A Cookbook for an IC Diet - Confident Choices: Customizing the IC Diet - The ICN Special Report on Diet	Intercystitis Interstitial cystitis is chronic inflammation of the wall of the urinary bladder. Inflammation can lead to scarring, pinpoint bleeding of the bladder wall, and a decreased bladder capacity. # Causes Because bacteria, fungi or viruses are rarely found in the urine of people with interstitial cystitis, the cause is unclear. Possible causes include: - An autoimmune response that occurs following a bacterial infection of the bladder - Bacteria that cling too tightly to the wall of the bladder to be detected in the urine - A "leaky" inner lining of the bladder that allows irritating substances in the urine to come into contact with the bladder wall # Risk Factors - Sex: female - History of childhood bladder problems # Symptoms The symptoms of interstitial cystitis vary from person to person. They can also occur in cycles. Some people experience periods of intense symptoms followed by periods of remission. Pain can be severe enough to keep people from working or even walking. Symptoms can include: - Discomfort, pain, or pressure in the bladder or pelvic area - Frequent need to urinate (up to 60 times per day in severe cases) - Urgent need to urinate - Pain during intercourse - Blood and pus in the urine - Shrunken bladder # Diagnosis A doctor will ask about your symptoms and medical history, and perform a physical exam. In addition, your urine will be tested for pus and bacteria. If bacteria are present in the urine, you will likely be diagnosed with acute cystitis—a typical bladder infection. If no bacteria are present, your doctor will likely do other tests. A diagnosis of interstitial cystitis will only be made after other conditions have been ruled out and a cystoscopy with bladder distention has been done. This consists of distending (stretching) the bladder to its full capacity by instilling gas or liquids through the cystoscope. A cystoscopy will help your doctor see if there is scarring, bleeding, or inflammation on the bladder wall. # Treatment There is no treatment to cure interstitial cystitis. Treatment is aimed at relieving symptoms. You may have to try several different treatments before you experience relief. Treatments include: ### Bladder Distention Some people experience relief after the bladder distention—done during the cystoscopy—is done. ### Bladder Instillation During bladder instillation, a "wash" is put into the bladder through a tube in the urethra. It is held for anywhere from a few seconds to 15 minutes and then voided. There are several different types of solutions used. Some coat the bladder and are thought to decrease the inflammation. ### Medication Medications may include: - Bladder coating - taken orally, they can coat and protect the bladder - Antidepressants and pain relievers - for pain relief - Antihistamines - may help stop the cycle of inflammation - Antispasmodics - may alleviate frequency and urgency of urination ### Diet Many people find that changes in diet can help relieve pain. Finally, in the Summer of 2006, researchers Barbara Shorter RD and Robert Moldwin MD provided concrete proof that diet does exacerbate IC symptoms when they released the preliminary data for the first formal research study on diet and IC in a lecture on the Interstitial Cystitis Network. Foods commonly reported to aggravate interstitial cystitis include: - Coffees (Regular & Decaf) - Teas (Regular, Green & Blended Herbals) - Chocolate - Artificial sweeteners - Alcohol - Acidic foods - Carbonated beverages ### Transcutaneous Electrical Nerve Stimulation (TENS) A Transcutaneous Electrical Nerve Stimulator, or TENS, is an external device that sends mild electrical impulses into the body. It has been helpful in relieving pain and decreasing frequency of urination in some people. ### Bladder Training Some people are able to train the bladder to have better control by setting a regular timed schedule for emptying their bladder. The amount of time between voidings is gradually increased. Bladder training should be attempted only after pain relief has been accomplished. ### Surgery Surgery is a treatment of last resort. It is used after all other treatment methods have been exhausted and if the pain is severe. Many people continue to have pain even after surgery. # Prevention There are no guidelines for preventing interstitial cystitis because the cause is unknown. # Organizations - Interstitial Cystitis Association - Interstitial Cystitis Network - ICU Texas - The Cystitis and Overactive Bladder Foundation - The Interstitial Cystitis Association # Resources - IC Patient Handbook In addition to traditional IC therapies, diet modification remains a core self help strategy as foods that are irritating to the bladder dramatically worsen the symptoms that patients may experience. Foods high in acid and/or caffeine (such as all coffees, regular teas, green teas, sodas, diet sodas, artificial sugars and most fruit juices) should be avoided. The daily goal of patients should be to soothe rather than irritate the bladder wall. - The Top Five List of Forbidden Foods - IC Survival Guide by Robert Moldwin, MD - A Taste of the Good Life: A Cookbook for an IC Diet - Confident Choices: Customizing the IC Diet - The ICN Special Report on Diet # External Links - Interstitial Cystitis Association - Interstitial Cystitis Network - Interstitial Cystitis Advice (A Patient Based Community for People with IC) Template:WikiDoc Sources	https://www.wikidoc.org/index.php/Intercystitis
c0e4a929f36225fc225882788ed826bd26cf48e8	wikidoc	Interleukin 1	Interleukin 1 Interleukin-1 (IL-1) is one of the first cytokines ever described. Its initial discovery was as a factor that could induce fever, control lymphocytes, increase the number of bone marrow cells and cause degeneration of bone joints. At this time, IL-1 was known under several other names including endogenous pyrogen, lymphocyte activating factor, haemopoetin-1 and mononuclear cell factor, amongst others. It was around 1984-1985 when scientists confirmed that IL-1 was actually composed of two distinct proteins, now called IL-1α and IL-1β. These belong to a family of cytokines known as the interleukin-1 superfamily. # The Interleukin-1 superfamily The original members of the IL-1 superfamily are IL-1α, IL-1β, and the IL-1 Receptor antagonist (IL-1RA). - IL-1α and -β are pro-inflammatory cytokines involved in immune defence against infection. - The IL-1RA is a molecule that competes for receptor binding with IL-1α and IL-1β, blocking their role in immune activation. Recent years have seen the addition of other molecules to the IL-1 superfamily including IL-18 and six more genes with structural homology to IL-1α, IL-1β or IL-1RA. These latter six members are named IL1F5, IL1F6, IL1F7, IL1F8, IL1F9, and IL1F10. In accord, IL-1α, IL-1β, and IL-1RA have been renamed IL-1F1, IL-1F2, and IL-1F3, respectively. A further putative member of the IL-1 family has been recently described that is called IL-33 or IL-1F11, although this name is not officially accepted in the HGNC gene family nomenclature database. ## IL-1α and IL-1β Both IL-1α and IL-1β are produced by macrophages, monocytes and dendritic cells. They form an important part of the inflammatory response of the body against infection. These cytokines increase the expression of adhesion factors on endothelial cells to enable transmigration of leukocytes, the cells that fight pathogens, to sites of infection and re-set the hypothalamus thermoregulatory center, leading to an increased body temperature which expresses itself as fever. IL-1 is therefore called an endogenous pyrogen. The increased body temperature helps the body's immune system to fight infection. IL-1 is also important in the regulation of hematopoiesis. IL-1β production in peripheral tissue has also been associated with hyperalgesia (increased sensitivity to pain) associated with fever. For the most part, these two forms of IL-1 bind to the same cellular receptor. This receptor is composed of two related, but non-identical, subunits that transmit intracellular signals via a pathway that is mostly shared with certain other receptors. These include the Toll family of innate immune receptors and the receptor for IL-18. IL-1α is a pleiotropic cytokine involved in various immune responses, inflammatory processes, and hematopoiesis. This cytokine is produced by many cell types but is only secreted by monocytes and macrophages. It is produced as a proprotein, which is proteolytically processed by calpain and released in a mechanism that is still not well studied. This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2. It has been suggested that the polymorphism of these genes is associated with rheumatoid arthritis and Alzheimer's disease. # Structure of the IL-1 superfamily IL-1α and IL-1β are produced as precursor peptides. In other words they are made as a long protein that is then processed to release a shorter, active molecule, which is called the mature protein. Mature IL-1β, for instance, is released from Pro-IL-1β following cleavage by a certain member of the caspase family of proteins, called caspase-1 or the interleukin-1 converting enzyme (ICE). The 3-dimensional structure of the mature forms of each member of the human IL-1 superfamily is composed of 12-14 β-strands producing a barrel-shaped protein.	Interleukin 1 Interleukin-1 (IL-1) is one of the first cytokines ever described. Its initial discovery was as a factor that could induce fever, control lymphocytes, increase the number of bone marrow cells and cause degeneration of bone joints. At this time, IL-1 was known under several other names including endogenous pyrogen, lymphocyte activating factor, haemopoetin-1 and mononuclear cell factor, amongst others. It was around 1984-1985 when scientists confirmed that IL-1 was actually composed of two distinct proteins, now called IL-1α and IL-1β.[1] These belong to a family of cytokines known as the interleukin-1 superfamily. # The Interleukin-1 superfamily The original members of the IL-1 superfamily are IL-1α, IL-1β, and the IL-1 Receptor antagonist (IL-1RA). - IL-1α and -β are pro-inflammatory cytokines involved in immune defence against infection. - The IL-1RA is a molecule that competes for receptor binding with IL-1α and IL-1β, blocking their role in immune activation. Recent years have seen the addition of other molecules to the IL-1 superfamily including IL-18[2] and six more genes with structural homology to IL-1α, IL-1β or IL-1RA. These latter six members are named IL1F5, IL1F6, IL1F7, IL1F8, IL1F9, and IL1F10. In accord, IL-1α, IL-1β, and IL-1RA have been renamed IL-1F1, IL-1F2, and IL-1F3, respectively.[3][4] A further putative member of the IL-1 family has been recently described that is called IL-33 or IL-1F11, although this name is not officially accepted in the HGNC gene family nomenclature database.[5] ## IL-1α and IL-1β Both IL-1α and IL-1β are produced by macrophages, monocytes and dendritic cells. They form an important part of the inflammatory response of the body against infection. These cytokines increase the expression of adhesion factors on endothelial cells to enable transmigration of leukocytes, the cells that fight pathogens, to sites of infection and re-set the hypothalamus thermoregulatory center, leading to an increased body temperature which expresses itself as fever. IL-1 is therefore called an endogenous pyrogen. The increased body temperature helps the body's immune system to fight infection. IL-1 is also important in the regulation of hematopoiesis. IL-1β production in peripheral tissue has also been associated with hyperalgesia (increased sensitivity to pain) associated with fever.[6] For the most part, these two forms of IL-1 bind to the same cellular receptor. This receptor is composed of two related, but non-identical, subunits that transmit intracellular signals via a pathway that is mostly shared with certain other receptors. These include the Toll family of innate immune receptors and the receptor for IL-18. IL-1α is a pleiotropic cytokine involved in various immune responses, inflammatory processes, and hematopoiesis. This cytokine is produced by many cell types but is only secreted by monocytes and macrophages. It is produced as a proprotein, which is proteolytically processed by calpain and released in a mechanism that is still not well studied. This gene and eight other interleukin 1 family genes form a cytokine gene cluster on chromosome 2. It has been suggested that the polymorphism of these genes is associated with rheumatoid arthritis and Alzheimer's disease. # Structure of the IL-1 superfamily IL-1α and IL-1β are produced as precursor peptides. In other words they are made as a long protein that is then processed to release a shorter, active molecule, which is called the mature protein. Mature IL-1β, for instance, is released from Pro-IL-1β following cleavage by a certain member of the caspase family of proteins, called caspase-1 or the interleukin-1 converting enzyme (ICE). The 3-dimensional structure of the mature forms of each member of the human IL-1 superfamily is composed of 12-14 β-strands producing a barrel-shaped protein.[1]	https://www.wikidoc.org/index.php/Interleukin-1
0c0870710104d62f1ebe8c1b366b51e31ab226a7	wikidoc	Interleukin 3	Interleukin 3 Interleukin 3 (IL-3) is a protein that in humans is encoded by the IL3 gene. # Function Interleukin 3 is an interleukin, a type of biological signal (cytokine) that can improve the body's natural response to disease as part of the immune system. It acts by binding to the interleukin-3 receptor. Interleukin 3 stimulates the differentiation of multipotent hematopoietic stem cells into myeloid progenitor cells or, with the addition of IL-7, into lymphoid progenitor cells. In addition, IL-3 stimulates proliferation of all cells in the myeloid lineage (granulocytes, monocytes, and dendritic cells), in conjunction with other cytokines, e.g., Erythropoietin (EPO), Granulocyte macrophage colony-stimulating factor (GM-CSF), and IL-6. It is secreted by basophils and activated T cells to support growth and differentiation of T cells from the bone marrow in an immune response. Activated T cells can either induce their own proliferation and differentiation (autocrine signalling), or that of other T cells (paracrine signalling) – both involve IL-2 binding to the IL-2 receptor on T cells (upregulated upon cell activation, under the induction of macrophage-secreted IL-1). The human IL-3 gene encodes a protein 152 amino acids long, and the naturally occurring IL-3 is glycosylated. The human IL-3 gene is located on chromosome 5, only 9 kilobases from the GM-CSF gene, and its function is quite similar to GM-CSF. # Discovery Interleukin 3 originally was discovered by JN Ihle in mice. He found a T cell derived factor that induced the synthesis of 20alpha-hydroxysteroid dehydrogenase in hematopoietic cells and termed it interleukin-3. # Interactions Interleukin 3 has been shown to interact with IL3RA.	Interleukin 3 Interleukin 3 (IL-3) is a protein that in humans is encoded by the IL3 gene.[1][2] # Function Interleukin 3 is an interleukin, a type of biological signal (cytokine) that can improve the body's natural response to disease as part of the immune system. It acts by binding to the interleukin-3 receptor. Interleukin 3 stimulates the differentiation of multipotent hematopoietic stem cells into myeloid progenitor cells or, with the addition of IL-7, into lymphoid progenitor cells. In addition, IL-3 stimulates proliferation of all cells in the myeloid lineage (granulocytes, monocytes, and dendritic cells), in conjunction with other cytokines, e.g., Erythropoietin (EPO), Granulocyte macrophage colony-stimulating factor (GM-CSF), and IL-6. It is secreted by basophils and activated T cells to support growth and differentiation of T cells from the bone marrow in an immune response. Activated T cells can either induce their own proliferation and differentiation (autocrine signalling), or that of other T cells (paracrine signalling) – both involve IL-2 binding to the IL-2 receptor on T cells (upregulated upon cell activation, under the induction of macrophage-secreted IL-1). The human IL-3 gene encodes a protein 152 amino acids long, and the naturally occurring IL-3 is glycosylated. The human IL-3 gene is located on chromosome 5, only 9 kilobases from the GM-CSF gene, and its function is quite similar to GM-CSF. # Discovery Interleukin 3 originally was discovered by JN Ihle in mice. He found a T cell derived factor that induced the synthesis of 20alpha-hydroxysteroid dehydrogenase in hematopoietic cells and termed it interleukin-3.[3][4] # Interactions Interleukin 3 has been shown to interact with IL3RA.[5][6]	https://www.wikidoc.org/index.php/Interleukin-3
ebcd9a38638eaa9dba0ff0796599ab87dc9c5721	wikidoc	Interpolation	Interpolation In the mathematical subfield of numerical analysis, interpolation is a method of constructing new data points within the range of a discrete set of known data points. In engineering and science one often has a number of data points, as obtained by sampling or experiment, and tries to construct a function which closely fits those data points. This is called curve fitting or regression analysis. Interpolation is a specific case of curve fitting, in which the function must go exactly through the data points. A different problem which is closely related to interpolation is the approximation of a complicated function by a simple function. Suppose we know the function but it is too complex to evaluate efficiently. Then we could pick a few known data points from the complicated function, creating a lookup table, and try to interpolate those data points to construct a simpler function. Of course, when using the simple function to calculate new data points we usually do not receive the same result as when using the original function, but depending on the problem domain and the interpolation method used the gain in simplicity might offset the error. It should be mentioned that there is another very different kind of interpolation in mathematics, namely the "interpolation of operators". The classical results about interpolation of operators are the Riesz-Thorin theorem and the Marcinkiewicz theorem. There also are many other subsequent results. # Definition From inter meaning between and pole, the points or nodes. Any means of calculating a new point between two existing data points is therefore interpolation. There are many methods for doing this, many of which involve fitting some sort of function to the data and evaluating that function at the desired point. This does not exclude other means such as statistical methods of calculating interpolated data. The simplest form of interpolation is to take the mean average of x and y of two adjacent points to find the mid point. This will give the same result as linear interpolation evaluated at the midpoint. Given a sequence of n distinct numbers xk called nodes and for each xk a second number yk, we are looking for a function f so that A pair xk,yk is called a data point and f is called an interpolant for the data points. When the numbers yk are given by a known function f, we sometimes write fk. # Example For example, suppose we have a table like this, which gives some values of an unknown function f. Interpolation provides a means of estimating the function at intermediate points, such as x = 2.5. There are many different interpolation methods, some of which are described below. Some of the concerns to take into account when choosing an appropriate algorithm are: How accurate is the method? How expensive is it? How smooth is the interpolant? How many data points are needed? # Piecewise constant interpolation The simplest interpolation method is to locate the nearest data value, and assign the same value. In one dimension, there are seldom good reasons to choose this one over linear interpolation, which is almost as cheap, but in higher dimensions, in multivariate interpolation, this can be a favourable choice for its speed and simplicity. # Linear interpolation One of the simplest methods is linear interpolation (sometimes known as lerp). Consider the above example of determining f(2.5). Since 2.5 is midway between 2 and 3, it is reasonable to take f(2.5) midway between f(2) = 0.9093 and f(3) = 0.1411, which yields 0.5252. Generally, linear interpolation takes two data points, say (xa,ya) and (xb,yb), and the interpolant is given by: Linear interpolation is quick and easy, but it is not very precise. Another disadvantage is that the interpolant is not differentiable at the point xk. The following error estimate shows that linear interpolation is not very precise. Denote the function which we want to interpolate by g, and suppose that x lies between xa and xb and that g is twice continuously differentiable. Then the linear interpolation error is In words, the error is proportional to the square of the distance between the data points. The error of some other methods, including polynomial interpolation and spline interpolation (described below), is proportional to higher powers of the distance between the data points. These methods also produce smoother interpolants. # Polynomial interpolation Polynomial interpolation is a generalization of linear interpolation. Note that the linear interpolant is a linear function. We now replace this interpolant by a polynomial of higher degree. Consider again the problem given above. The following sixth degree polynomial goes through all the seven points: Substituting x = 2.5, we find that f(2.5) = 0.5965. Generally, if we have n data points, there is exactly one polynomial of degree at most n−1 going through all the data points. The interpolation error is proportional to the distance between the data points to the power n. Furthermore, the interpolant is a polynomial and thus infinitely differentiable. So, we see that polynomial interpolation solves all the problems of linear interpolation. However, polynomial interpolation also has some disadvantages. Calculating the interpolating polynomial is relatively very computationally expensive (see computational complexity). Furthermore, polynomial interpolation may not be so exact after all, especially at the end points (see Runge's phenomenon). These disadvantages can be avoided by using spline interpolation. # Spline interpolation Remember that linear interpolation uses a linear function for each of intervals . Spline interpolation uses low-degree polynomials in each of the intervals, and chooses the polynomial pieces such that they fit smoothly together. The resulting function is called a spline. For instance, the natural cubic spline is piecewise cubic and twice continuously differentiable. Furthermore, its second derivative is zero at the end points. The natural cubic spline interpolating the points in the table above is given by -0.1522 x^3 + 0.9937 x, & \mbox{if } x \in , \\ -0.01258 x^3 - 0.4189 x^2 + 1.4126 x - 0.1396, & \mbox{if } x \in , \\ 0.1403 x^3 - 1.3359 x^2 + 3.2467 x - 1.3623, & \mbox{if } x \in , \\ 0.1579 x^3 - 1.4945 x^2 + 3.7225 x - 1.8381, & \mbox{if } x \in , \\ 0.05375 x^3 -0.2450 x^2 - 1.2756 x + 4.8259, & \mbox{if } x \in , \\ -0.1871 x^3 + 3.3673 x^2 - 19.3370 x + 34.9282, & \mbox{if } x \in . \\ \end{matrix} \right. In this case we get f(2.5)=0.597262. Like polynomial interpolation, spline interpolation incurs a smaller error than linear interpolation and the interpolant is smoother. However, the interpolant is easier to evaluate than the high-degree polynomials used in polynomial interpolation. It also does not suffer from Runge's phenomenon. # Other forms of interpolation Other forms of interpolation can be constructed by picking a different class of interpolants. For instance, rational interpolation is interpolation by rational functions, and trigonometric interpolation is interpolation by trigonometric polynomials. The discrete Fourier transform is a special case of trigonometric interpolation. Another possibility is to use wavelets. The Whittaker–Shannon interpolation formula can be used if the number of data points is infinite. Multivariate interpolation is the interpolation of functions of more than one variable. Methods include bilinear interpolation and bicubic interpolation in two dimensions, and trilinear interpolation in three dimensions. Sometimes, we know not only the value of the function that we want to interpolate, at some points, but also its derivative. This leads to Hermite interpolation problems. # Related concepts The term extrapolation is used if we want to find data points outside the range of known data points. In curve fitting problems, the constraint that the interpolant has to go exactly through the data points is relaxed. It is only required to approach the data points as closely as possible. This requires parameterizing the potential interpolants and having some way of measuring the error. In the simplest case this leads to least squares approximation. Approximation theory studies how to find the best approximation to a given function by another function from some predetermined class, and how good this approximation is. This clearly yields a bound on how well the interpolant can approximate the unknown function.	Interpolation In the mathematical subfield of numerical analysis, interpolation is a method of constructing new data points within the range of a discrete set of known data points. In engineering and science one often has a number of data points, as obtained by sampling or experiment, and tries to construct a function which closely fits those data points. This is called curve fitting or regression analysis. Interpolation is a specific case of curve fitting, in which the function must go exactly through the data points. A different problem which is closely related to interpolation is the approximation of a complicated function by a simple function. Suppose we know the function but it is too complex to evaluate efficiently. Then we could pick a few known data points from the complicated function, creating a lookup table, and try to interpolate those data points to construct a simpler function. Of course, when using the simple function to calculate new data points we usually do not receive the same result as when using the original function, but depending on the problem domain and the interpolation method used the gain in simplicity might offset the error. It should be mentioned that there is another very different kind of interpolation in mathematics, namely the "interpolation of operators". The classical results about interpolation of operators are the Riesz-Thorin theorem and the Marcinkiewicz theorem. There also are many other subsequent results. # Definition From inter meaning between and pole, the points or nodes. Any means of calculating a new point between two existing data points is therefore interpolation. There are many methods for doing this, many of which involve fitting some sort of function to the data and evaluating that function at the desired point. This does not exclude other means such as statistical methods of calculating interpolated data. The simplest form of interpolation is to take the mean average of <math>x</math> and <math>y</math> of two adjacent points to find the mid point. This will give the same result as linear interpolation evaluated at the midpoint. Given a sequence of n distinct numbers xk called nodes and for each xk a second number yk, we are looking for a function f so that A pair xk,yk is called a data point and f is called an interpolant for the data points. When the numbers yk are given by a known function f, we sometimes write fk. # Example For example, suppose we have a table like this, which gives some values of an unknown function f. Interpolation provides a means of estimating the function at intermediate points, such as x = 2.5. There are many different interpolation methods, some of which are described below. Some of the concerns to take into account when choosing an appropriate algorithm are: How accurate is the method? How expensive is it? How smooth is the interpolant? How many data points are needed? # Piecewise constant interpolation The simplest interpolation method is to locate the nearest data value, and assign the same value. In one dimension, there are seldom good reasons to choose this one over linear interpolation, which is almost as cheap, but in higher dimensions, in multivariate interpolation, this can be a favourable choice for its speed and simplicity. # Linear interpolation One of the simplest methods is linear interpolation (sometimes known as lerp). Consider the above example of determining f(2.5). Since 2.5 is midway between 2 and 3, it is reasonable to take f(2.5) midway between f(2) = 0.9093 and f(3) = 0.1411, which yields 0.5252. Generally, linear interpolation takes two data points, say (xa,ya) and (xb,yb), and the interpolant is given by: Linear interpolation is quick and easy, but it is not very precise. Another disadvantage is that the interpolant is not differentiable at the point xk. The following error estimate shows that linear interpolation is not very precise. Denote the function which we want to interpolate by g, and suppose that x lies between xa and xb and that g is twice continuously differentiable. Then the linear interpolation error is In words, the error is proportional to the square of the distance between the data points. The error of some other methods, including polynomial interpolation and spline interpolation (described below), is proportional to higher powers of the distance between the data points. These methods also produce smoother interpolants. # Polynomial interpolation Polynomial interpolation is a generalization of linear interpolation. Note that the linear interpolant is a linear function. We now replace this interpolant by a polynomial of higher degree. Consider again the problem given above. The following sixth degree polynomial goes through all the seven points: Substituting x = 2.5, we find that f(2.5) = 0.5965. Generally, if we have n data points, there is exactly one polynomial of degree at most n−1 going through all the data points. The interpolation error is proportional to the distance between the data points to the power n. Furthermore, the interpolant is a polynomial and thus infinitely differentiable. So, we see that polynomial interpolation solves all the problems of linear interpolation. However, polynomial interpolation also has some disadvantages. Calculating the interpolating polynomial is relatively very computationally expensive (see computational complexity). Furthermore, polynomial interpolation may not be so exact after all, especially at the end points (see Runge's phenomenon). These disadvantages can be avoided by using spline interpolation. # Spline interpolation Remember that linear interpolation uses a linear function for each of intervals [xk,xk+1]. Spline interpolation uses low-degree polynomials in each of the intervals, and chooses the polynomial pieces such that they fit smoothly together. The resulting function is called a spline. For instance, the natural cubic spline is piecewise cubic and twice continuously differentiable. Furthermore, its second derivative is zero at the end points. The natural cubic spline interpolating the points in the table above is given by -0.1522 x^3 + 0.9937 x, & \mbox{if } x \in [0,1], \\ -0.01258 x^3 - 0.4189 x^2 + 1.4126 x - 0.1396, & \mbox{if } x \in [1,2], \\ 0.1403 x^3 - 1.3359 x^2 + 3.2467 x - 1.3623, & \mbox{if } x \in [2,3], \\ 0.1579 x^3 - 1.4945 x^2 + 3.7225 x - 1.8381, & \mbox{if } x \in [3,4], \\ 0.05375 x^3 -0.2450 x^2 - 1.2756 x + 4.8259, & \mbox{if } x \in [4,5], \\ -0.1871 x^3 + 3.3673 x^2 - 19.3370 x + 34.9282, & \mbox{if } x \in [5,6]. \\ \end{matrix} \right. </math> In this case we get f(2.5)=0.597262. Like polynomial interpolation, spline interpolation incurs a smaller error than linear interpolation and the interpolant is smoother. However, the interpolant is easier to evaluate than the high-degree polynomials used in polynomial interpolation. It also does not suffer from Runge's phenomenon. # Other forms of interpolation Other forms of interpolation can be constructed by picking a different class of interpolants. For instance, rational interpolation is interpolation by rational functions, and trigonometric interpolation is interpolation by trigonometric polynomials. The discrete Fourier transform is a special case of trigonometric interpolation. Another possibility is to use wavelets. The Whittaker–Shannon interpolation formula can be used if the number of data points is infinite. Multivariate interpolation is the interpolation of functions of more than one variable. Methods include bilinear interpolation and bicubic interpolation in two dimensions, and trilinear interpolation in three dimensions. Sometimes, we know not only the value of the function that we want to interpolate, at some points, but also its derivative. This leads to Hermite interpolation problems. # Related concepts The term extrapolation is used if we want to find data points outside the range of known data points. In curve fitting problems, the constraint that the interpolant has to go exactly through the data points is relaxed. It is only required to approach the data points as closely as possible. This requires parameterizing the potential interpolants and having some way of measuring the error. In the simplest case this leads to least squares approximation. Approximation theory studies how to find the best approximation to a given function by another function from some predetermined class, and how good this approximation is. This clearly yields a bound on how well the interpolant can approximate the unknown function.	https://www.wikidoc.org/index.php/Interpolation
2aac250e61bf79ffd78f6a59712e36a5e071d03d	wikidoc	Intracellular	Intracellular # Overview In cell biology, molecular biology and related fields, the word intracellular means "inside the cell". It is used in contrast to extracellular (outside the cell). The cell membrane (and, in plants, the cell wall) is the barrier between the two, and chemical composition of intra- and extracellular milieu can be radically different. In most organisms, for example, a Na+/K+ ATPase maintains a high potassium level inside cells while keeping sodium low, leading to chemical excitability. note: do not get confused between intracellular and intercellular, the latter meaning "between cells".	Intracellular # Overview In cell biology, molecular biology and related fields, the word intracellular means "inside the cell". It is used in contrast to extracellular (outside the cell). The cell membrane (and, in plants, the cell wall) is the barrier between the two, and chemical composition of intra- and extracellular milieu can be radically different. In most organisms, for example, a Na+/K+ ATPase maintains a high potassium level inside cells while keeping sodium low, leading to chemical excitability. note: do not get confused between intracellular and intercellular, the latter meaning "between cells". Template:WH Template:WikiDoc Sources	https://www.wikidoc.org/index.php/Intracellular
f58490d941a83126372176e59760fa588e7b951f	wikidoc	Introspection	Introspection Introspection is the mental self-observation reporting of conscious inner thoughts, desires and sensations. It is a conscious mental and usually purposive process relying on thinking, reasoning, and examining one's own thoughts feelings, and, in more spiritual cases, one's soul. It can also be called contemplation of one's self, and is contrasted with extrospection, the observation of things external to one's self. Introspection may be used synonymously with self-reflection and used in a similar way. Behaviorists claimed that introspection was unreliable and that the subject matter of scientific psychology should be strictly operationalized in an objective and measurable way. This then led psychology to focus on measurable behavior rather than consciousness or sensation. Cognitive psychology accepts the use of the scientific method, but rejects introspection as a valid method of investigation for this reason. It should be noted that Herbert Simon and Allen Newell identified the 'thinking-aloud' protocol, in which investigators view a subject engaged in introspection, and who speaks his thoughts aloud, thus allowing study of his introspection. On the other hand, introspection can be considered a valid tool for the development of scientific hypotheses and theoretical models, in particular, in cognitive sciences and engineering. In practice, functional (goal-oriented) computational modeling and computer simulation design of meta-reasoning and metacognition are closely connected with the introspective experiences of researchers and engineers. Introspection was used by German physiologist Wilhelm Wundt in the experimental psychology laboratory he had founded in Leipzig in 1879. Wundt believed that by using introspection in his experiments he would gather information into how the subjects' minds were working, thus he wanted to examine the mind into its basic elements. Wundt did not invent this way of looking into an individual's mind through their experiences; rather, it can date to Socrates. Wundt's distinctive contribution was to take this method into the experimental arena and thus into the newly formed field of psychology. # In fiction Introspection (also referred to as internal dialogue, interior monologue, self-talk) is the fiction-writing mode used to convey a character's thoughts. As explained by Renni Browne and Dave King, "One of the great gifts of literature is that it allows for the expression of unexpressed thoughts…" Template:Harvard citation. According to Nancy Kress, a character's thoughts can greatly enhance a story: deepening characterization, increasing tension, and widening the scope of a story Template:Harvard citation. As outlined by Jack M. Bickham, thought plays a critical role in both scene and sequel Template:Harvard citation. Among authors and writing coaches, there appears to be little consensus regarding the importance of introspection and how it is best presented.	Introspection Introspection is the mental self-observation reporting of conscious inner thoughts, desires and sensations. It is a conscious mental and usually purposive process relying on thinking, reasoning, and examining one's own thoughts feelings, and, in more spiritual cases, one's soul. It can also be called contemplation of one's self, and is contrasted with extrospection, the observation of things external to one's self. Introspection may be used synonymously with self-reflection and used in a similar way. Behaviorists claimed that introspection was unreliable and that the subject matter of scientific psychology should be strictly operationalized in an objective and measurable way. This then led psychology to focus on measurable behavior rather than consciousness or sensation.[1] Cognitive psychology accepts the use of the scientific method, but rejects introspection as a valid method of investigation for this reason. It should be noted that Herbert Simon and Allen Newell identified the 'thinking-aloud' protocol, in which investigators view a subject engaged in introspection, and who speaks his thoughts aloud, thus allowing study of his introspection. On the other hand, introspection can be considered a valid tool for the development of scientific hypotheses and theoretical models, in particular, in cognitive sciences and engineering. In practice, functional (goal-oriented) computational modeling and computer simulation design of meta-reasoning and metacognition are closely connected with the introspective experiences of researchers and engineers. Introspection was used by German physiologist Wilhelm Wundt in the experimental psychology laboratory he had founded in Leipzig in 1879. Wundt believed that by using introspection in his experiments he would gather information into how the subjects' minds were working, thus he wanted to examine the mind into its basic elements. Wundt did not invent this way of looking into an individual's mind through their experiences; rather, it can date to Socrates. Wundt's distinctive contribution was to take this method into the experimental arena and thus into the newly formed field of psychology. # In fiction Introspection (also referred to as internal dialogue, interior monologue, self-talk) is the fiction-writing mode used to convey a character's thoughts. As explained by Renni Browne and Dave King, "One of the great gifts of literature is that it allows for the expression of unexpressed thoughts…" Template:Harvard citation. According to Nancy Kress, a character's thoughts can greatly enhance a story: deepening characterization, increasing tension, and widening the scope of a story Template:Harvard citation. As outlined by Jack M. Bickham, thought plays a critical role in both scene and sequel Template:Harvard citation. Among authors and writing coaches, there appears to be little consensus regarding the importance of introspection [2] and how it is best presented.[3]	https://www.wikidoc.org/index.php/Introspection
adb6a0ab701fd3d8d9e8c8d0584f4135be334daa	wikidoc	Iridocyclitis	Iridocyclitis # Overview Iridocyclitis a type of anterior uveitis, is a condition in which the uvea has an acute inflammation. # Pathophysiology & Etiology Iridocyclitis is usually caused by direct exposure of the eyes to chemicals, particularly lacrimators, but can also be caused by ocular viral infection such as herpes zoster (i.e. herpetic iridocyclitis). There are six classifications of iridocyclitis. Acute or Chronic - Acute: sudden symptomatic onset, lasting no more than six weeks. - Chronic: Persisting for more than six weeks, possibly asymptomatic. Chronic iridocyclitis is usually associated with systemic disorders including ankylosing spondylitis, Behçet's syndrome, inflammatory bowel disease, juvenile rheumatoid arthritis, Reiter's syndrome, sarcoidosis, syphilis, tuberculosis, and Lyme disease. Exogenous or Endogenous - Exogenous: related to external damage to the uvea or invasion of external microorganisms. - Endogenous: related to internal microbes. Granulomatous or Non-granulomatous - Granulomatous: accompanied by large keratotic precipitates. - Non-granulomatous: accompanied by smaller keratotic precipitates. # History and Symptoms - photophobia - redness - watering of the eyes - lacrimation - miosis, constriction of the pupil - blurred vision - Synechia # Treatment # Pharmacotherapy It can be effectively treated with tropane alkaloids or steroids. To immobilize the iris and decrease pain, one may find tropane alkaloids effective, particularly scopolamine and atropine in 0.25% and 1% concentrations respectively. Topical steroids may be used to decrease inflammation, particularly prednisolone and dexamethasone.	Iridocyclitis Template:DiseaseDisorder infobox Template:Search infobox Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview Iridocyclitis a type of anterior uveitis, is a condition in which the uvea has an acute inflammation. # Pathophysiology & Etiology Iridocyclitis is usually caused by direct exposure of the eyes to chemicals, particularly lacrimators, but can also be caused by ocular viral infection such as herpes zoster (i.e. herpetic iridocyclitis). There are six classifications of iridocyclitis. Acute or Chronic - Acute: sudden symptomatic onset, lasting no more than six weeks. - Chronic: Persisting for more than six weeks, possibly asymptomatic. Chronic iridocyclitis is usually associated with systemic disorders including ankylosing spondylitis, Behçet's syndrome, inflammatory bowel disease, juvenile rheumatoid arthritis, Reiter's syndrome, sarcoidosis, syphilis, tuberculosis, and Lyme disease. Exogenous or Endogenous - Exogenous: related to external damage to the uvea or invasion of external microorganisms. - Endogenous: related to internal microbes. Granulomatous or Non-granulomatous - Granulomatous: accompanied by large keratotic precipitates. - Non-granulomatous: accompanied by smaller keratotic precipitates. # History and Symptoms - photophobia - redness - watering of the eyes - lacrimation - miosis, constriction of the pupil - blurred vision - Synechia # Treatment # Pharmacotherapy It can be effectively treated with tropane alkaloids or steroids. To immobilize the iris and decrease pain, one may find tropane alkaloids effective, particularly scopolamine and atropine in 0.25% and 1% concentrations respectively. Topical steroids may be used to decrease inflammation, particularly prednisolone and dexamethasone.	https://www.wikidoc.org/index.php/Iridocyclitis
7f1c2cc78d9ccfb4bc5334f2aeb30638b58c3aaf	wikidoc	Iridodialysis	Iridodialysis # Overview Iridodialysis, sometimes known as a coredialysis, is a localized separation or tearing away of the iris from its attachment to the ciliary body. # Causes Iridodialyses are usually caused by blunt trauma to the eye, but may also be caused by penetrating eye injuries. An iridodialysis may be an iatrogenic complication of any intraocular surgery and at one time they were created intentionally as part of intracapsular cataract extraction. Iridodialyses have been reported to have occurred from boxing, airbag deployments, high-pressure water jets, elastic bungee cords, bottle caps opened under pressure, water balloons, fireworks, and various types of balls. # Symptoms and signs Those with small iridodialyses may be asymptomatic and require no treatment, but those with larger dialyses may have corectopia or polycoria and experience monocular diplopia, glare, or photophobia. Iridodialyses often accompany angle recession and may cause glaucoma or hyphema. Hypotony may also occur. # Treatment and management Iridodialysis causing an associated hyphema has to be carefully managed, and recurrent bleeds should be prevented by strict avoidance of all sporting activities. Management typically involves observation and bed rest. Red blood cells may decrease the outflow of aqueous humor, therefore the eye should be kept soft by giving oral acetazolamide. Accidental trauma during sleep should be prevented by patching with an eye shield during night time. Avoid giving aspirin, heparin/warfarin and observe daily for resolution or progression. A large hyphema may require careful anterior chamber washout. Rebleeds may require additional intervention and therapy. Later, surgical repair may be considered for larger avulsions causing significant double vision, cosmesis or glare symptoms. Surgical repair is usually done by 10-0 prolene suture taking the base of iris avulsion and suturing it to the scleral spur and ciliary body junction. # Complications Those with traumatic iridodialyses (particularly by blunt eye trauma) are at high risk for angle recession, thereby causing increased intraocular pressure (IOP). This is typically seen about 100 days or three months after the injury, and is thereby called 100 day Glaucoma. Medical or surgical treatment to control the IOP may be required if glaucoma is present. Soft opaque contact lenses may be used to improve cosmesis and reduce the perception of double vision.	Iridodialysis # Overview Iridodialysis, sometimes known as a coredialysis, is a localized separation or tearing away of the iris from its attachment to the ciliary body.[1][2] # Causes Iridodialyses are usually caused by blunt trauma to the eye,[2] but may also be caused by penetrating eye injuries.[3] An iridodialysis may be an iatrogenic complication of any intraocular surgery[4][5][6] and at one time they were created intentionally as part of intracapsular cataract extraction.[7] Iridodialyses have been reported to have occurred from boxing,[8] airbag deployments,[9] high-pressure water jets,[10] elastic bungee cords,[11][12] bottle caps opened under pressure,[13] water balloons,[14] fireworks[15][16], and various types of balls.[17] # Symptoms and signs Those with small iridodialyses may be asymptomatic and require no treatment, but those with larger dialyses may have corectopia or polycoria and experience monocular diplopia, glare, or photophobia.[18][19][20] Iridodialyses often accompany angle recession[21] and may cause glaucoma[3] or hyphema.[22] Hypotony may also occur.[23] # Treatment and management Iridodialysis causing an associated hyphema has to be carefully managed, and recurrent bleeds should be prevented by strict avoidance of all sporting activities. Management typically involves observation and bed rest. Red blood cells may decrease the outflow of aqueous humor, therefore the eye should be kept soft by giving oral acetazolamide. Accidental trauma during sleep should be prevented by patching with an eye shield during night time. Avoid giving aspirin, heparin/warfarin and observe daily for resolution or progression. A large hyphema may require careful anterior chamber washout. Rebleeds may require additional intervention and therapy. Later, surgical repair may be considered for larger avulsions causing significant double vision, cosmesis or glare symptoms.[19] Surgical repair is usually done by 10-0 prolene suture taking the base of iris avulsion and suturing it to the scleral spur and ciliary body junction. # Complications Those with traumatic iridodialyses (particularly by blunt eye trauma) are at high risk for angle recession, thereby causing increased intraocular pressure (IOP).[18] This is typically seen about 100 days or three months after the injury, and is thereby called 100 day Glaucoma. Medical or surgical treatment to control the IOP may be required if glaucoma is present.[3] Soft opaque contact lenses may be used to improve cosmesis and reduce the perception of double vision.[3][18]	https://www.wikidoc.org/index.php/Iridodialysis
4d7930d4899a71963aa5eb645dd74e9f55edecd0	wikidoc	Isocarboxazid	Isocarboxazid # Disclaimer WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here. # Black Box Warning # Overview Isocarboxazid is a MAOI that is FDA approved for the {{{indicationType}}} of depression. There is a Black Box Warning for this drug as shown here. Common adverse reactions include constipation, nausea, xerostomia, dizziness, headache, insomnia.. # Adult Indications and Dosage ## FDA-Labeled Indications and Dosage (Adult) - Depression - Initial: 20 mg/day PO into 2 doses, increase every 2-4 days by 10 mg, to a maximum of 40 mg in first week. Then increase to 20 mg/week to a max of 60 mg/day. - Maintenance: Decrease dose slowly to minimum effective dosage ## Off-Label Use and Dosage (Adult) ### Guideline-Supported Use There is limited information about Off-Label Guideline-Supported Use of Isocarboxazid in adult patients. ### Non–Guideline-Supported Use There is limited information about Off-Label Non–Guideline-Supported Use of Isocarboxazid in adult patients. # Pediatric Indications and Dosage ## FDA-Labeled Indications and Dosage (Pediatric) safety in under 16 years of age have not been established. ## Off-Label Use and Dosage (Pediatric) ### Guideline-Supported Use There is limited information about Off-Label Guideline-Supported Use of Isocarboxazid in pediatric patients. ### Non–Guideline-Supported Use There is limited information about Off-Label Non–Guideline-Supported Use of Isocarboxazid in pediatric patients. # Contraindications There is limited information regarding Isocarboxazid Contraindications in the drug label. # Warnings There is limited information regarding Isocarboxazid Warnings' in the drug label. # Adverse Reactions ## Clinical Trials Experience There is limited information regarding Isocarboxazid Clinical Trials Experience in the drug label. ## Postmarketing Experience There is limited information regarding Isocarboxazid Postmarketing Experience in the drug label. # Drug Interactions There is limited information regarding Isocarboxazid Drug Interactions in the drug label. # Use in Specific Populations ### Pregnancy Pregnancy Category (FDA): There is no FDA guidance on usage of Isocarboxazid in women who are pregnant. Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Isocarboxazid in women who are pregnant. ### Labor and Delivery There is no FDA guidance on use of Isocarboxazid during labor and delivery. ### Nursing Mothers There is no FDA guidance on the use of Isocarboxazid in women who are nursing. ### Pediatric Use There is no FDA guidance on the use of Isocarboxazid in pediatric settings. ### Geriatic Use There is no FDA guidance on the use of Isocarboxazid in geriatric settings. ### Gender There is no FDA guidance on the use of Isocarboxazid with respect to specific gender populations. ### Race There is no FDA guidance on the use of Isocarboxazid with respect to specific racial populations. ### Renal Impairment There is no FDA guidance on the use of Isocarboxazid in patients with renal impairment. ### Hepatic Impairment There is no FDA guidance on the use of Isocarboxazid in patients with hepatic impairment. ### Females of Reproductive Potential and Males There is no FDA guidance on the use of Isocarboxazid in women of reproductive potentials and males. ### Immunocompromised Patients There is no FDA guidance one the use of Isocarboxazid in patients who are immunocompromised. # Administration and Monitoring ### Administration There is limited information regarding Isocarboxazid Administration in the drug label. ### Monitoring There is limited information regarding Isocarboxazid Monitoring in the drug label. # IV Compatibility There is limited information regarding the compatibility of Isocarboxazid and IV administrations. # Overdosage There is limited information regarding Isocarboxazid overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately. # Pharmacology ## Mechanism of Action There is limited information regarding Isocarboxazid Mechanism of Action in the drug label. ## Structure There is limited information regarding Isocarboxazid Structure in the drug label. ## Pharmacodynamics There is limited information regarding Isocarboxazid Pharmacodynamics in the drug label. ## Pharmacokinetics There is limited information regarding Isocarboxazid Pharmacokinetics in the drug label. ## Nonclinical Toxicology There is limited information regarding Isocarboxazid Nonclinical Toxicology in the drug label. # Clinical Studies There is limited information regarding Isocarboxazid Clinical Studies in the drug label. # How Supplied There is limited information regarding Isocarboxazid How Supplied in the drug label. ## Storage There is limited information regarding Isocarboxazid Storage in the drug label. # Images ## Drug Images ## Package and Label Display Panel # Patient Counseling Information (Patient Counseling Information) # Precautions with Alcohol Alcohol-Isocarboxazid interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication. # Brand Names There is limited information regarding Isocarboxazid Brand Names in the drug label. # Look-Alike Drug Names There is limited information regarding Isocarboxazid Look-Alike Drug Names in the drug label. # Drug Shortage Status Drug Shortage # Price	Isocarboxazid Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Pratik Bahekar, MBBS [2] # Disclaimer WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here. # Black Box Warning # Overview Isocarboxazid is a MAOI that is FDA approved for the {{{indicationType}}} of depression. There is a Black Box Warning for this drug as shown here. Common adverse reactions include constipation, nausea, xerostomia, dizziness, headache, insomnia.. # Adult Indications and Dosage ## FDA-Labeled Indications and Dosage (Adult) - Depression - Initial: 20 mg/day PO into 2 doses, increase every 2-4 days by 10 mg, to a maximum of 40 mg in first week. Then increase to 20 mg/week to a max of 60 mg/day. - Maintenance: Decrease dose slowly to minimum effective dosage ## Off-Label Use and Dosage (Adult) ### Guideline-Supported Use There is limited information about Off-Label Guideline-Supported Use of Isocarboxazid in adult patients. ### Non–Guideline-Supported Use There is limited information about Off-Label Non–Guideline-Supported Use of Isocarboxazid in adult patients. # Pediatric Indications and Dosage ## FDA-Labeled Indications and Dosage (Pediatric) safety in under 16 years of age have not been established. ## Off-Label Use and Dosage (Pediatric) ### Guideline-Supported Use There is limited information about Off-Label Guideline-Supported Use of Isocarboxazid in pediatric patients. ### Non–Guideline-Supported Use There is limited information about Off-Label Non–Guideline-Supported Use of Isocarboxazid in pediatric patients. # Contraindications There is limited information regarding Isocarboxazid Contraindications in the drug label. # Warnings There is limited information regarding Isocarboxazid Warnings' in the drug label. # Adverse Reactions ## Clinical Trials Experience There is limited information regarding Isocarboxazid Clinical Trials Experience in the drug label. ## Postmarketing Experience There is limited information regarding Isocarboxazid Postmarketing Experience in the drug label. # Drug Interactions There is limited information regarding Isocarboxazid Drug Interactions in the drug label. # Use in Specific Populations ### Pregnancy Pregnancy Category (FDA): There is no FDA guidance on usage of Isocarboxazid in women who are pregnant. Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Isocarboxazid in women who are pregnant. ### Labor and Delivery There is no FDA guidance on use of Isocarboxazid during labor and delivery. ### Nursing Mothers There is no FDA guidance on the use of Isocarboxazid in women who are nursing. ### Pediatric Use There is no FDA guidance on the use of Isocarboxazid in pediatric settings. ### Geriatic Use There is no FDA guidance on the use of Isocarboxazid in geriatric settings. ### Gender There is no FDA guidance on the use of Isocarboxazid with respect to specific gender populations. ### Race There is no FDA guidance on the use of Isocarboxazid with respect to specific racial populations. ### Renal Impairment There is no FDA guidance on the use of Isocarboxazid in patients with renal impairment. ### Hepatic Impairment There is no FDA guidance on the use of Isocarboxazid in patients with hepatic impairment. ### Females of Reproductive Potential and Males There is no FDA guidance on the use of Isocarboxazid in women of reproductive potentials and males. ### Immunocompromised Patients There is no FDA guidance one the use of Isocarboxazid in patients who are immunocompromised. # Administration and Monitoring ### Administration There is limited information regarding Isocarboxazid Administration in the drug label. ### Monitoring There is limited information regarding Isocarboxazid Monitoring in the drug label. # IV Compatibility There is limited information regarding the compatibility of Isocarboxazid and IV administrations. # Overdosage There is limited information regarding Isocarboxazid overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately. # Pharmacology Template:Drugbox 2 ## Mechanism of Action There is limited information regarding Isocarboxazid Mechanism of Action in the drug label. ## Structure There is limited information regarding Isocarboxazid Structure in the drug label. ## Pharmacodynamics There is limited information regarding Isocarboxazid Pharmacodynamics in the drug label. ## Pharmacokinetics There is limited information regarding Isocarboxazid Pharmacokinetics in the drug label. ## Nonclinical Toxicology There is limited information regarding Isocarboxazid Nonclinical Toxicology in the drug label. # Clinical Studies There is limited information regarding Isocarboxazid Clinical Studies in the drug label. # How Supplied There is limited information regarding Isocarboxazid How Supplied in the drug label. ## Storage There is limited information regarding Isocarboxazid Storage in the drug label. # Images ## Drug Images ## Package and Label Display Panel # Patient Counseling Information (Patient Counseling Information) # Precautions with Alcohol Alcohol-Isocarboxazid interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication. # Brand Names There is limited information regarding Isocarboxazid Brand Names in the drug label. # Look-Alike Drug Names There is limited information regarding Isocarboxazid Look-Alike Drug Names in the drug label. # Drug Shortage Status Drug Shortage # Price	https://www.wikidoc.org/index.php/Isocarboxazid
5345647a29865a3eb6f87d95a50dda3862a06eca	wikidoc	Isomerisation	Isomerisation In chemistry, isomerization or isomerisation is the transformation of a molecule into a different isomer . In some molecules and under some conditions, isomerisation occurs spontaneously. Many isomers are equal or roughly equal in bond energy, and so they interconvert relatively freely. When the isomerisation occurs intramolecularly it is considered a rearrangement reaction. # Instances of Isomerization - Isomerisations in hydrocarbon cracking. This is usually employed in organic chemistry, where fuels, such as pentane, a straight-chain isomer, are heated in the presence of a platinum catalyst (see image). The resulting mixture of straight- and branched-chain isomers then have to be separated. An industrial process is also the isomerisation of n-butane into isobutane. Nota Bene: the first product should be 2-methylbutane, rather than 2-methylpentane. - Trans-cis isomerism. In certain compounds an interconversion of cis and trans isomers can be observed, for instance, with maleic acid and with azobenzene often by photoisomerization. An example is the photochemical conversion of the trans isomer to the cis isomer of resveratrol : - Aldose-ketose isomerism in biochemistry. - Isomerisations between conformational isomers. These take place without an actual rearrangement for instance inconversion of two cyclohexane conformations - Fluxional molecules display rapid interconversion of isomers. The energy difference between two isomers is called isomerisation energy. Isomerisations with low energy difference both experimental and computational (in parentheses) are endothermic trans-cis isomerisation of 2-butene with 2.6 (1.2) kcal/mol, cracking of isopentane to n-pentane with 3.6 (4.0) kcal/mol or conversion of trans-2-butene to 1-butene with 2.6 (2.4) kcal/mol.	Isomerisation In chemistry, isomerization or isomerisation is the transformation of a molecule into a different isomer [1]. In some molecules and under some conditions, isomerisation occurs spontaneously. Many isomers are equal or roughly equal in bond energy, and so they interconvert relatively freely. When the isomerisation occurs intramolecularly it is considered a rearrangement reaction. # Instances of Isomerization - Isomerisations in hydrocarbon cracking. This is usually employed in organic chemistry, where fuels, such as pentane, a straight-chain isomer, are heated in the presence of a platinum catalyst (see image). The resulting mixture of straight- and branched-chain isomers then have to be separated. An industrial process is also the isomerisation of n-butane into isobutane. Nota Bene: the first product should be 2-methylbutane, rather than 2-methylpentane. - Trans-cis isomerism. In certain compounds an interconversion of cis and trans isomers can be observed, for instance, with maleic acid and with azobenzene often by photoisomerization. An example is the photochemical conversion of the trans isomer to the cis isomer of resveratrol [2]: - Aldose-ketose isomerism in biochemistry. - Isomerisations between conformational isomers. These take place without an actual rearrangement for instance inconversion of two cyclohexane conformations - Fluxional molecules display rapid interconversion of isomers. The energy difference between two isomers is called isomerisation energy. Isomerisations with low energy difference both experimental and computational (in parentheses) are endothermic trans-cis isomerisation of 2-butene with 2.6 (1.2) kcal/mol, cracking of isopentane to n-pentane with 3.6 (4.0) kcal/mol or conversion of trans-2-butene to 1-butene with 2.6 (2.4) kcal/mol.[3]	https://www.wikidoc.org/index.php/Isomerisation
da70edee4d4db6a4c21a70a09b1a1a4c13165e82	wikidoc	Isoproscaline	Isoproscaline Isoproscaline (or 4-(i)-propyl-3,5-dimethoxyphenethylamine) is an analogue of mescaline. It is closely related to proscaline and was first synthesized by David E. Nichols. It produces hallucinogenic, psychedelic, and entheogenic effects. # Chemistry Isoproscaline is in a class of compounds commonly known as phenethylamines, and the full chemical name is 2-(4-isopropoxy-3,5-dimethoxyphenyl)ethanamine. # Effects Little is known about the psychopharmacological effects of isoproscaline. Shulgin lists a psychedelic dosage as being 40-80 mg, with effects lasting 12-18 hours. # Pharmacology The mechanism that produces the hallucinogenic and entheogenic effects of isoproscaline is most likely to result from action as a 5-HT2A serotonin receptor agonist in the brain, a mechanism of action shared by all of the hallucinogenic tryptamines and phenethylamines. # Dangers The toxicity of isoproscaline is not known. # Legality Isoproscaline is unscheduled and unregulated in the United States, however because of its close similarity in structure and effects to mescaline, possession and sale of isoproscaline may be subject to prosecution under the Federal Analog Act.	Isoproscaline Isoproscaline (or 4-(i)-propyl-3,5-dimethoxyphenethylamine) is an analogue of mescaline. It is closely related to proscaline and was first synthesized by David E. Nichols. It produces hallucinogenic, psychedelic, and entheogenic effects. # Chemistry Isoproscaline is in a class of compounds commonly known as phenethylamines, and the full chemical name is 2-(4-isopropoxy-3,5-dimethoxyphenyl)ethanamine. # Effects Little is known about the psychopharmacological effects of isoproscaline. Shulgin lists a psychedelic dosage as being 40-80 mg, with effects lasting 12-18 hours. # Pharmacology The mechanism that produces the hallucinogenic and entheogenic effects of isoproscaline is most likely to result from action as a 5-HT2A serotonin receptor agonist in the brain, a mechanism of action shared by all of the hallucinogenic tryptamines and phenethylamines. # Dangers The toxicity of isoproscaline is not known. # Legality Isoproscaline is unscheduled and unregulated in the United States, however because of its close similarity in structure and effects to mescaline, possession and sale of isoproscaline may be subject to prosecution under the Federal Analog Act.	https://www.wikidoc.org/index.php/Isoproscaline

Subsets and Splits

No community queries yet

The top public SQL queries from the community will appear here once available.