Зміни активності NO-синтаз та аргінази у тканині підшлункової залози при введенні L-аргініну або аміногуанідину за умов стрептозотоцин-індукованої гіперглікемії

При стрептозотоцин-индуцированной гипергликемии у крыс изучали влияние L-аргинина и селективного блокатора индуцибельной NO-синтазы аминогунидина на активность NO-синтаз и аргиназы в ткани поджелудочной железы. Показано, что как L-аргинин, так и аминогуанидин снижают активность индуцибельной NO-синтазы, при этом L-аргинин выражено понижает концентрацию глюкозы в крови и повышает активность аргиназы, что свидетельствует об усилении неокислительного пути его метаболизма.The influence of L-arginine and selective inducible NO-synthase blocker aminoguanidine on the activity of NO-synthases and arginase in pancreatic tissue in rats under conditions of streptozotocin-induced hyperglycemia was investigated. It was shown, that both L-arginine and aminoguanidine decrease the activity of inducible NO-synthase, whereas L-arginine supplementation significantly decreases the glucose concentration in blood and increases the activity of arginase, giving evidence about the enhancement of nonoxidative pathway of its metabolism

Genetic variability of von Willebrand factor and risk of coronary heart disease: the Rotterdam Study.

The von Willebrand factor (VWF) may be causally associated with coronary heart disease (CHD) or merely be a marker of endothelial damage. The G allele of the -1793 C/G promoter polymorphism in the VWF gene has been associated with higher plasma levels of VWF. To investigate whether VWF has a causal role in CHD, we designed a case-cohort study, including 352 subjects with CHD and a random cohort (n = 736), and prospectively examined the association of the -1793 C/G polymorphism with CHD in subjects with and without advanced atherosclerosis. All subjects were </=75 years of age and participating in the population-based Rotterdam Study. Atherosclerosis was assessed by the ankle-arm index. Among subjects with advanced atherosclerosis, heterozygous and homozygous carriers of the G allele had a 3.5 (1.2-10.2) and 1.5 (0.4-5.7) fold increased risk of CHD respectively, compared with C/C homozygotes. The hazard ratio was 2.6 (1.0-6.8) for carriers of at least one copy of the G allele versus non-carriers. No associations were found in the absence of advanced atherosclerosis. In conclusion, this study suggests that the G allele of the -1793 C/G polymorphism in the VWF gene is associated with an increased risk of CHD, but only in subjects with advanced atherosclerosis

Is there a direct association between age-related eye diseases and mortality? The Rotterdam Study

To study mortality in subjects with age-related maculopathy (ARM), cataract, or open-angle glaucoma (OAG) in comparison with those without these disorders. Population-based prospective cohort study. Subjects (n = 6339) aged 55 years and older from the population-based Rotterdam Study for whom complete information on eye disease status was present. Vital status continuously monitored from 1990 until January 1, 2000. The diagnosis of ARM was made according to the International Classification System. Cataract, determined on biomicroscopy, was defined as any sign of nuclear or (sub)cortical cataract, or both, in at least one eye with a visual acuity of 20/40 or less. Aphakia and pseudophakia in at least one eye were classified as operated cataract. Definite OAG was defined as a glaucomatous optic neuropathy combined with a glaucomatous visual field defect. Diagnoses were assessed at baseline. Mortality hazard ratios were computed using Cox proportional hazard regression analysis, adjusted for appropriate confounders (age, gender, smoking status, body mass index, cholesterol level, atherosclerosis, hypertension, history of cardiovascular disease, and diabetes mellitus). The adjusted mortality hazard ratio for subjects with AMD (n = 104) was 0.94 (95% confidence interval [CI], 0.52-1.68), with biomicroscopic cataract (n = 951) was 0.94 (95% CI, 0.74-1.21), with surgical cataract (n = 298) was 1.20 (95% CI, 0.86-1.68), and with definite OAG (n = 44) was 0.39 (95% CI, 0.10-1.55). Both ARM and cataract are predictors of shorter survival because they have risk factors that also affect mortality. When adjusted for these factors, ARM, cataract, and OAG were themselves not significantly associated with mortalit

Aortic stiffness is associated with atherosclerosis of the coronary arteries in older adults:the Rotterdam Study

Objective Aortic stiffness can lead to low diastolic blood pressure, thereby possibly limiting coronary perfusion. Therefore, the simultaneous occurrence of both aortic stiffness and coronary atherosclerosis can lead to an increased risk of subendocardial ischaemia. The aim of the present study was to investigate the association between aortic stiffness and coronary atherosclerosis. Methods The study was performed in 1757 subjects of the Rotterdam Study, a population-based study of elderly individuals. Aortic stiffness was assessed by measuring carotid-femoral pulse wave velocity (PWV). Coronary atherosclerosis was assessed by measuring coronary calcification using electron beam tomography and expressed as a total calcium score. The total calcium score was log-transformed because of its skewed distribution. The association between PWV and coronary calcification was first evaluated after adjustment for age, sex, mean arterial blood pressure and heart rate. Results Linear regression analyses showed that increased PWV was associated with a higher log total coronary calcium score [beta-regression coefficient 0.11, 95% confidence interval (CI) 0.07-0.15]. Compared with the lowest quartile of PWV, multivariate odds ratios and corresponding 95% CI for advanced coronary calcification in the second, third and fourth highest quartiles were 1.17 (0.79-1.74), 1.58 (1.07-2.34) and 2.12 (1.40-3.20), respectively. Conclusions In this large population-based study performed in elderly subjects aortic stiffness was strongly and independently associated with coronary atherosclerosis