Circulating markers of arterial thrombosis and late-stage age-related macular degeneration: a case-control study.

PURPOSE: The aim of this study was to examine the relation of late-stage age-related macular degeneration (AMD) with markers of systemic atherothrombosis. METHODS: A hospital-based case-control study of AMD was undertaken in London, UK. Cases of AMD (n=81) and controls (n=77) were group matched for age and sex. Standard protocols were used for colour fundus photography and to classify AMD; physical examination included height, weight, history of or treatment for vascular-related diseases and smoking status. Blood samples were taken for measurement of fibrinogen, factor VIIc (FVIIc), factor VIIIc, prothrombin fragment F1.2 (F1.2), tissue plasminogen activator, and von Willebrand factor. Odds ratios from logistic regression analyses of each atherothrombotic marker with AMD were adjusted for age, sex, and established cardiovascular disease risk factors, including smoking, blood pressure, body mass index, and total cholesterol. RESULTS: After adjustment FVIIc and possibly F1.2 were inversely associated with the risk of AMD; per 1 standard deviation increase in these markers the odds ratio were, respectively, 0.62 (95% confidence interval 0.40, 0.95) and 0.71 (0.46, 1.09). None of the other atherothrombotic risk factors appeared to be related to AMD status. There was weak evidence that aspirin is associated with a lower risk of AMD. CONCLUSIONS: This study does not provide strong evidence of associations between AMD and systematic markers of arterial thrombosis, but the potential effects of FVIIc, and F1.2 are worthy of further investigation

Risk factors for cataract subtypes waterclefts and retrodots: two case-control studies.

UNLABELLED: Waterclefts and retrodots are independently associated with visual impairment, yet a review identified no data on risk factors. PURPOSE: To investigate risk factors for these two human lens cataract subtypes. METHOD: Two nested case-control studies: The host study comprised 1078 subjects (55 years) attending the Somerset and Avon Eye Study (SAES). In total, 197 watercleft cases (Oxford grade 0.2 in either eye) and 199 retrodot cases (Oxford grade 1.0 in either eye) were individually age/gender matched to controls. Detailed ophthalmic and potential risk factor data were collected, including body mass index (BMI), smoking, alcohol, diabetes, hypertension, analgesics, vitamin supplementation, nutrition, sunlight exposure, dehydration, hormonal (women), blood lipids, glucose, urea, creatinine, uric acid, and vitamin levels. RESULTS: For waterclefts, univariable analysis identified BMI, alcohol intake, vitamin status, sunlight, urea, creatinine, and uric acid as possible risk factors. Multivariable analysis identified two independent associations. Total number of 'any' analgesics in the previous year: adjusted P<0.01 (U-shaped risk profile, unadjusted high vs medium use (=reference) OR 2.39, 95% CI 1.35-4.26 with medium use vs none (=reference) OR 0.43, 95% CI 0.26-0.72); total sunlight: adjusted P=0.03 (unadjusted highest exposure vs lowest (=reference) OR 3.25, 95% CI 1.11-9.50). For retrodots, univariable analysis identified alcohol, HRT, and lipids. Multivariable analysis identified two independent associations. Mean number of alcohol units consumed per month, adjusted P=0.02 and HDL cholesterol levels, adjusted P=0.02 (unadjusted ORs NS both). CONCLUSION: This is the first available published information on risk factors for the human cataractous lens features waterclefts and retrodots

Flavianate, an amino acid precipitant, is a competitive inhibitor of trypsin at pH 3.0

Textile dyes bind to proteins leading to selective co-precipitation of a complex involving one protein molecule and more than one dye molecule of opposite charge in acid solutions, in a process of reversible denaturation that can be utilized for protein fractionation. In order to understand what occurs before the co-precipitation, a kinetic study using bovine ß-trypsin and sodium flavianate was carried out based on reaction progress curve techniques. The experiments were carried out using <FONT FACE="Symbol">a</font>-CBZ-L-Lys-p-nitrophenyl ester as substrate which was added to 50 mM sodium citrate buffer, pH 3.0, containing varying concentrations of ß-trypsin and dye. The reaction was recorded spectrophotometrically at 340 nm for 30 min, and the families of curves obtained were analyzed simultaneously by fitting integrated Michaelis-Menten equations. The dye used behaved as a competitive inhibitor of trypsin at pH 3.0, with Ki = 99 µM; kinetic parameters for the substrate hydrolysis were: Km = 32 µM, and kcat = 0.38/min. The competitive character of the inhibition suggests a specific binding of the first dye molecule to His-57, the only positively charged residue at the active site of the enzyme