A Collaborative Study Designed to Establish the 4th International Standard for Heparin

Thomas, Duncan P.; Curtis, A. D. M.; Barrowcliffe, Trevor W.

doi:10.1055/s-0038-1661160

Cited by 27 publications

(18 citation statements)

References 1 publication

(1 reference statement)

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“…Heparin and Protein Biotinylation-For the biotinylation of unfractionated heparin (the 4th International Standard (4IS) (26,27)), 13 l of a 25 mg/ml solution of 1-ethyl-3-(3-dimethylaminopropyl)carbo-dimide hydrochloride (Sigma, Poole, UK) in 0.1 M MES, pH 6.5, was added to 7.91 mg of 4IS heparin in 1 ml of 0.1 M MES buffer, pH 6.5. Then 20 ml of 50 mM biotin-LC-hydrazide (Pierce, Northumberland, UK) in dimethylsulphoxide (freshly made) was added to the heparin/1-ethyl-3-(3-dimethylaminopropyl)carbo-dimide hydrochloride reaction and left to mix by rotation at room temperature overnight.…”

Section: Methodsmentioning

confidence: 99%

His-384 Allotypic Variant of Factor H Associated with Age-related Macular Degeneration Has Different Heparin Binding Properties from the Non-disease-associated Form

Clark

Higman

Mulloy

et al. 2006

Journal of Biological Chemistry

167

214

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A polymorphism in complement factor H has recently been associated with age-related macular degeneration (AMD), the leading cause of blindness in the elderly. A histidine rather than a tyrosine at residue position 384 in the mature protein increases the risk of AMD. Here, using a recombinant construct, we show that amino acid 384 is adjacent to a heparin-binding site in CCP7 of factor H and demonstrate that the allotypic variants differentially recognize heparin. This functional alteration may affect binding of factor H to polyanionic patterns on host surfaces, potentially influencing complement activation, immune complex clearance, and inflammation in the macula of AMD patients. Age-related macular degeneration (AMD)4 is the leading cause of natural blindness in the Western world, and its prevalence may become greater with an increasing elderly population (1, 2). AMD manifests itself by the progressive destruction of the macula, causing central vision loss. The dry form of AMD, which accounts for 90% of cases, is associated with the presence of small yellow "drusen" deposits between the choroid and the retinal pigment epithelium that result in gradual vision loss; about 10 -20% of patients with dry AMD go on to develop the more severe wet form. Recently, a common allelic variant of human complement factor H (3) has been linked to an increased risk of developing dry AMD (4 -6). This variant arises from a tyrosine/histidine polymorphism at amino acid 384 in the mature protein (referred to as residue 402 in Refs. 4 -6), where ϳ35% of individuals of European descent carry the disease-associated His-384 allele. This increases the likelihood of developing AMD by 2.7-fold and may account for 50% of the attributable risk of AMD (4). In individuals who are homozygous for the risk allele, the likelihood of AMD is increased by a factor of 7.4 (5). Recently, the His-384 allele has also been associated with an increased risk of myocardial infarction, where it has been suggested that atherosclerosis could contribute to macular degeneration (7).Factor H is a 155-kDa plasma protein that acts as a cofactor for the breakdown of complement C3b by factor I (8). It is composed of 20 complement control protein (CCP; also termed short consensus repeats) modules (9), each of ϳ60 amino acids with a compact structure (10). The Y384H polymorphism is located within CCP7 (3). Factor H is believed to discriminate self from non-self by recognizing polyanionic structures on the former, such as sialic acid and the glycosaminoglycan (GAG) chains of proteoglycans (e.g. heparan sulfate (HS) and dermatan sulfate (DS)) and thus inhibits complement activation on host surfaces (11,12). Factor H has been shown to be present in retinal blood vessels in the choroid (5) and is associated with the drusen of AMD patients (2, 13). In addition, markers of complement activation (e.g. C5b-9 and C3 fragments, including iC3b) have been detected in the Bruch's membrane and drusen of AMD patients, leading to the hypothesis that AMD results from an aberrant inflamm...

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Section: Methodsmentioning

confidence: 99%

His-384 Allotypic Variant of Factor H Associated with Age-related Macular Degeneration Has Different Heparin Binding Properties from the Non-disease-associated Form

Clark

Higman

Mulloy

et al. 2006

Journal of Biological Chemistry

167

214

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“…19,20,25 Para cada ensaio, efetuou-se a análise de variância demonstrando ser a regressão significativa (p<0,05), e os desvios de linearidade e paralelismo, não significativos. Observa-se também que cada amostra forneceu resultados específicos, alguns dos quais fora dos limites estabelecidos, e, em geral, inferior ao ICPO.…”

Section: Discussionunclassified

“…18,20,25,30 Realizou-se a avaliação de produtos farmacêuticos comerciais obtendo-se potên-cias entre 80,41% e 112,15%, (Tabela 4). Os produtos cumprem os requisitos farmacopéicos que preconizam atividade entre 80-125%.…”

Section: Discussionunclassified

“…A literatura 20,31 registra diferenças inferiores a 3,5% em estudos colaborativos pelos mé-todos do TTPA e anti-fator Xa, podendo-se deduzir que os dados aqui apresentados foram reprodutíveis.…”

Section: Discussionunclassified

“…A geração atual de heparinas tem massas moleculares médias mais elevadas e distribuição em faixa mais estreita, observada pela maior atividade específica, entre 180 e 210 UI/mg. [20][21][22][23] O presente trabalho teve por objetivos realizar a avaliação comparativa de potência de heparinas convencionais pelas metodologias preconizadas para o controle da qualidade e, ao mesmo tempo, correlacionar com o ensaio padronizado do anti-fator IIa, avaliado como alternativa harmonizada, contribuindo assim para aprimorar e assegurar a eficácia clínica desses medicamentos.…”

Section: Introductionunclassified

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Avaliação comparativa da atividade biológica de heparinas não-fracionadas em produtos farmacêuticos

Vaccari¹,

Júnior²,

Masiero³

et al. 2003

Rev. Bras. Hematol. Hemoter.

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Realizou-se a avaliação biológica de potência de heparinas convencionais contra o 5º Padrão IntroduçãoAs heparinas convencionais, não-fracionadas, são usadas clinicamente para profilaxia e tratamento de trombose venosa, devido às suas propriedades anticoagulantes. Recentemente foram desenvolvidas e encontram-se disponíveis as heparinas de baixo peso molecular com eficácia antitrombótica, menos complicações hemorrágicas e redução da freqüência de injeções.Estruturalmente, as heparinas são glicosaminoglicanos sulfatados de peso molecular variável, compostos de unidades de glicosamina e ácido hexurônico, que se alternam unidas por ligações glicosídicas. O polímero apresenta micro-heterogeneidade estrutural devido à sulfatação e acetilação variáveis, bem como a distribuição das unidades de ácido hexurônico, mas a atividade biológica é semelhante.

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Standardisation of Unfractionated and Low-Molecular-Weight Heparin

Gray

2011

Heparin - A Century of Progress

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Unfractionated and low-molecular-weight heparins are complex biologicals. Standardisation and global harmonisation of units and methods of measurement are essential for safety and efficacy of this important class of anticoagulants. This chapter describes the traceability of the international unit and current status of the relationship between the international and pharmacopoeial standards, together with a review on current pharmacopoeial assay methods.

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A Collaborative Study Designed to Establish the 4th International Standard for Heparin

Cited by 27 publications

References 1 publication

His-384 Allotypic Variant of Factor H Associated with Age-related Macular Degeneration Has Different Heparin Binding Properties from the Non-disease-associated Form

His-384 Allotypic Variant of Factor H Associated with Age-related Macular Degeneration Has Different Heparin Binding Properties from the Non-disease-associated Form

Avaliação comparativa da atividade biológica de heparinas não-fracionadas em produtos farmacêuticos

Standardisation of Unfractionated and Low-Molecular-Weight Heparin

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