Ассоциация аллельных полиморфизмов гена эндотелиальной NO-синтазы с развитием ишемической болезни сердца (литературный обзор)

Проведений аналіз вітчизняних та закордонних досліджень стосовно вивчення впливу Т-786С, G894T, 4a/b поліморфізмів гену eNOS на ризик розвитку ІХС у представників різних популяцій. Доведена роль Т-786 С поліморфізма гену eNOS у розвитку ІХС у представників японської, української, італійської популяції, причому в останніх він пов’язаний із багатосудинним ураженням. G894T поліморфізм гену eNOS пов’язаний із підвищеним ризиком розвитку ІХС, ішемічних інсультів в італійській, турецькій, азіатській популяціях, а в російській ─ із рестенозами стентів. Доведений зв’язок 4а/4b поліморфізму гену eNOS із виникненням ІХС у турецькій, японській, корейській, афро-американській, іранській, російській популяціях, а в японській популяції ─ гендерна специфіка даної асоціації. В окремих дослідженнях отримані суперечливі дані щодо впливу Т-786 С поліморфізму гену eNOS в турецькій популяції. Не виявлено асоціації 4а/4b поліморфізму гену eNOS у чоловіків Словенії, Фінляндії, G894T поліморфізму гену eNOS у корейській популяції, а у представників білої австралійської популяцій не виявлено асоціації генотипів 4а/4b, G894T, Т-786С поліморфізму гену eNOS із ризиком розвитку ІХС.В статье проведен анализ отечественных и зарубежных исследований, посвященных изучению влияния Т-786С, G894T, 4a/b полиморфизмов гена eNOS на риск развития ИБС у представителей различных популяций. Доказана роль Т-786 С полиморфизма гена eNOS в развитии ИБС у представителей японской, украинськой, итальянской популяции, причем у последних он связан с многососудистым поражением. G894T полиморфизм гена eNOS связан с повышеным риском развития ИХС, ишемических инсультов в итальянской, турецкой, азиатской популяциях, а в российской ─ с рестенозами стентов. Доказана связь 4а/4b полиморфизма гена eNOS с возникновением ИБС в турецкой, японской, корейской, афро-американской, иранськой, российской популяциях, а в японской популяции ─ гендерная специфика данной ассоциации. В отдельных исследованиях получены противоречивые данные о влиянии Т-786 С полиморфизма гена eNOS в турецкой популяции. Не выявлено ассоциации 4а/4b полиморфизма гена eNOS у мужчин Словении, Финляндии, G894T полиморфизма гена eNOS в корейской популяции, а у представителей белой австралийской популяции не выявлено ассоциации генотипов 4а/4b, G894T, Т-786С полиморфизму гену eNOS с риском развития ИБС.The article analyzed Ukrainian and foreign research on the impact study T-786С, G894T, 4a /b polymorphisms of the eNOS gene on the risk of coronary artery disease (CAD) among representatives of different populations. The role of T-786C polimorphism of the eNOS gene was proven in the development of CAD among Japanese, Ukrainian, Italian population, and in the past it is associated with multivessel disease. G894T polymorphism of the eNOS gene is associated with high risk of CAD, ischemic stroke in Italian, Turkish, Asian populations. In the Russian population this polymorphism assotiated with restenosis of stents. The 4a/4b polymorphism of the eNOS gene has significant influence on risk of CAD in Turkish, Japanese, Korean, AfricanAmerican, Iranian and Russian populations. Japanese population has gender specificity of the association. Conflicting data obtained in separate studies of the influence of T-786C polymorphism of the eNOS gene in the Turkish population. There was no association 4a /4b polymorphism of the eNOS gene in men Slovenia’s men and in Finland. Wasn’t identify association of G894T polymorphism of the eNOS gene in Korean population. Wasn’t detected association of genotypes 4a/4b, G894T, T-786S of the eNOS gene polymorphisms with risk of CAD in white Australians. Due to the existence of common pathogenetic mechanisms, involving NO, polymorphism eNOS gene presence may increases the risk of developing COPD. So perspective is study of polymorphisms eNOS gene in patients with COPD and CAD of Ukrainian population. Investigate their role as candidate genes can help to predict and prevent the appearance of comorbid disorders

Association between serum uric acid, aortic, carotid and femoral stiffness among adults aged 40-75 years without and with type 2 diabetes mellitus: The Maastricht Study

Objective: Arterial stiffness may be a mechanism to explain the association between uric acid and cardiovascular disease. We aimed to analyse associations between serum uric acid and regional and local arterial stiffness, and assess potential differences related to sex and glucose metabolism status. Methods: A cross-sectional study was performed in 614 adults [52.6% men; mean age 58.7 +/- 8.5 years; 23.2% type 2 diabetes mellitus (by design)] from The Maastricht Study. Arterial stiffness was assessed by carotid-femoral pulse wave velocity (cfPWV), distensibility, and compliance coefficient of the carotid and femoral artery, and carotid artery Young's elastic modulus. Results: Higher uric acid (per SD of 74 mu mol/l) was associated with greater stiffness indicated by a significantly higher cfPWV [beta = 0.216 (95% confidence interval 0.061, 0.372); P = 0.006] and lower carotid distensibility coefficient [beta = -0.633 (95% confidence interval -1.099, -0.166); P = 0.008] after adjustment for sex, age, and glucose metabolism status. Associations lost significance after adjusting for mean arterial pressure, BMI, waist, smoking status, heart rate, total : high-density lipoprotein cholesterol ratio, triglycerides, estimated glomerular filtration rate, use of lipid-lowering, antihypertensive, and diabetes medication, and use of secondary uricosurics. No associations were found between uric acid and carotid compliance coefficient, carotid Young's elastic modulus, or stiffness of the femoral artery. A significant interaction (P <0.10) with glucose metabolism status was found for cfPWV. However, none of the stratified associations were significant. There was no interaction with sex. Conclusion: Uric acid was not significantly associated with stiffness of the aorta, or the carotid or femoral artery among adults aged 40-75 years without and with type 2 diabetes mellitus

Веб-ресурс для перегляду 3D моделей з використанням технології WebGL

У першому розділі досліджується актуальність проблеми, проводиться аналіз існуючих аналогів. Другий розділ присвячений формування мети дипломної роботи та задач проекту, вибору засобів реалізації та плануванню робіт. У третьому розділі виконується проектування веб-ресурсу, де наведені діаграми у нотації IDF0 та Use Case.Останній розділ присвячений детальному опису практичної реалізації проекту: виконання прототипування веб-сторінки, розмітка та форматування веб-ресурсу, налаштування та перевірка працездатності веб-браузера з WebGL, опис реакції на дії користувача, розробка функцій маніпуляцій над моделлю. Результатом проведеної роботи є розроблений веб-ресурс, який дозволяє користувачу обирати одну із чотирьох моделей для візуалізації на веб-сторінці та виконувати базові маніпуляції з нею

Associations of Advanced Glycation End-Products With Cognitive Functions in Individuals With and Without Type 2 Diabetes: The Maastricht Study

Context: Advanced glycation end-products (AGEs) are thought to be involved in the pathogenesis of Alzheimer's disease. AGEs are products resulting from nonenzymatic chemical reactions between reduced sugars and proteins, which accumulate during natural aging, and their accumulation is accelerated in hyperglycemic conditions such as type 2 diabetes mellitus. Objective: The objective of the study was to examine associations between AGEs and cognitive functions. Design, Setting, and Participants: This study was performed as part of the Maastricht Study, a population-based cohort study in which, by design, 215 participants (28.1%) had type 2 diabetes mellitus. Main Outcome Measures: We examined associations of skin autofluorescence (SAF) (n = 764), an overall estimate of skin AGEs, and specific plasma protein-bound AGEs (n = 781) with performance on tests for global cognitive functioning, information processing speed, verbal memory (immediate and delayed word recall), and response inhibition. Results: After adjustment for demographics, diabetes, smoking, alcohol, waist circumference, total cholesterol/high-density lipoprotein cholesterol ratio, triglycerides, and lipid-lowering medication use, higher SAF was significantly associated with worse delayed word recall (regression coefficient, b = - 0.44; P = .04), and response inhibition (b = 0.03; P = .04). After further adjustment for systolic blood pressure, cardiovascular disease, estimated glomerular filtration rate, and depression, associations were attenuated (delayed word recall, b = - 0.38, P = .07; response inhibition, b = 0.02, P = .07). Higher pentosidine levels were associated with worse global cognitive functioning (b = - 0.61; P = .04) after full adjustment, but other plasma AGEs were not. Associations did not differ between individuals with and without diabetes. Conclusion: We found inverse associations of SAF (a noninvasive marker for tissue AGEs) with cognitive performance, which were attenuated after adjustment for vascular risk factors and depression

Exercise SBP response and incident depressive symptoms: The Maastricht Study

Objective : An exaggerated exercise SBP, which is potentially modifiable, may be associated with incident depressive symptoms via an increased pulsatile pressure load on the brain. However, the association between exaggerated exercise SBP and incident depressive symptoms is unknown. Therefore, we examined whether exaggerated exercise SBP is associated with a higher risk of depressive symptoms over time. Methods : We used longitudinal data from the population-based Maastricht Study, with only individuals free of depressive symptoms at baseline included (n = 2121; 51.3% men; age 59.5 +/- 8.5 years). Exercise SBP was measured at baseline with a submaximal exercise cycle test. We calculated a composite score of exercise SBP based on four standardized exercise SBP measures: SBP at moderate workload, SBP at peak exercise, SBP change per minute during exercise and SBP 4 min after exercise. Clinically relevant depressive symptoms were determined annually at follow-up and defined as a Patient Health Questionnaire score of at least 10. Results : After a mean follow-up of 3.9 years, 175 participants (8.3%) had incident clinically relevant depressive symptoms. A 1 SD higher exercise SBP composite score was associated with a higher incidence of clinically relevant depressive symptoms [hazard ratio: 1.27 (95% confidence interval: 1.04-1.54)]. Results were adjusted for age, sex, education level, glucose metabolism status, lifestyle, cardiovascular risk factors, resting SBP and cardiorespiratory fitness. Conclusion : A higher exercise SBP response is associated with a higher incidence of clinically relevant depressive symptoms

Multiple inflammatory biomarker detection in a prospective cohort study: a cross-validation between well-established single-biomarker techniques and electrochemiluminescense-based multi-array platform

Background - In terms of time, effort and quality, multiplex technology is an attractive alternative for well-established single-biomarker measurements in clinical studies. However, limited data comparing these methods are available. Methods - We measured, in a large ongoing cohort study (n = 574), by means of both a 4-plex multi-array biomarker assay developed by MesoScaleDiscovery (MSD) and single-biomarker techniques (ELISA or immunoturbidimetric assay), the following biomarkers of low-grade inflammation: C-reactive protein (CRP), serum amyloid A (SAA), soluble intercellular adhesion molecule 1 (sICAM-1) and soluble vascular cell adhesion molecule 1 (sVCAM-1). These measures were realigned by weighted Deming regression and compared across a wide spectrum of subjects’ cardiovascular risk factors by ANOVA. Results - Despite that both methods ranked individuals’ levels of biomarkers very similarly (Pearson’s r all=0.755) absolute concentrations of all biomarkers differed significantly between methods. Equations retrieved by the Deming regression enabled proper realignment of the data to overcome these differences, such that intra-class correlation coefficients were then 0.996 (CRP), 0.711 (SAA), 0.895 (sICAM-1) and 0.858 (sVCAM-1). Additionally, individual biomarkers differed across categories of glucose metabolism, weight, metabolic syndrome and smoking status to a similar extent by either method. Conclusions - Multiple low-grade inflammatory biomarker data obtained by the 4-plex multi-array platform of MSD or by well-established single-biomarker methods are comparable after proper realignment of differences in absolute concentrations, and are equally associated with cardiovascular risk factors, regardless of such differences. Given its greater efficiency, the MSD platform is a potential tool for the quantification of multiple biomarkers of low-grade inflammation in large ongoing and future clinical studies

Sex disparities in cardiovascular risk factor assessment and screening for diabetes-related complications in individuals with diabetes: a systematic review

Background Insight in sex disparities in the detection of cardiovascular risk factors and diabetes-related complications may improve diabetes care. The aim of this systematic review is to study whether sex disparities exist in the assessment of cardiovascular risk factors and screening for diabetes-related complications.MethodsPubMed was systematically searched up to April 2020, followed by manual reference screening and citations checks (snowballing) using Google Scholar. Observational studies were included if they reported on the assessment of cardiovascular risk factors (HbA1c, lipids, blood pressure, smoking status, or BMI) and/or screening for nephropathy, retinopathy, or performance of feet examinations, in men and women with diabetes separately. Studies adjusting their analyses for at least age, or when age was considered as a covariable but left out from the final analyses for various reasons (i.e. backward selection), were included for qualitative analyses. No meta-analyses were planned because substantial heterogeneity between studies was expected. A modified Newcastle-Ottawa Quality Assessment Scale for cohort studies was used to assess risk of bias.ResultsOverall, 81 studies were included. The majority of the included studies were from Europe or North America (84%).The number of individuals per study ranged from 200 to 3,135,019 and data were extracted from various data sources in a variety of settings. Screening rates varied considerably across studies. For example, screening rates for retinopathy ranged from 13% to 90%, with half the studies reporting screening rates less than 50%. Mixed findings were found regarding the presence, magnitude, and direction of sex disparities with regard to the assessment of cardiovascular risk factors and screening for diabetes-related complications, with some evidence suggesting that women, compared with men, may be more likely to receive retinopathy screening and less likely to receive foot exams.ConclusionOverall, no consistent pattern favoring men or women was found with regard to the assessment of cardiovascular risk factors and screening for diabetes-related complications, and screening rates can be improved for both sexes.Public Health and primary carePrevention, Population and Disease management (PrePoD

Sex differences in the association of prediabetes and type 2 diabetes with microvascular complications and function: the Maastricht Study

Background Women with type 2 diabetes are disproportionally affected by macrovascular complications; we here investigated whether this is also the case for microvascular complications and retinal microvascular measures. Methods In a population-based cohort study of individuals aged 40-75 years (n = 3410; 49% women, 29% type 2 diabetes (oversampled by design)), we estimated sex-specific associations, and differences therein, of (pre)diabetes (reference: normal glucose metabolism), and of continuous measures of glycemia with microvascular complications and retinal measures (nephropathy, sensory neuropathy, and retinal arteriolar and venular diameters and dilatation). Sex differences were analyzed using regression models with interaction terms (i.e. sex-by- (pre)diabetes and sex-by-glycemia) and were adjusted for potential confounders. Results Men with type 2 diabetes (but not those with prediabetes) compared to men with normal glucose metabolism, (and men with higher levels of glycemia), had significantly higher prevalences of nephropathy (odds ratio: 1.58 95% CI (1.01;2.46)) and sensory neuropathy (odds ratio: 2.46 (1.67;3.63)), larger retinal arteriolar diameters (difference: 4.29 mu m (1.22;7.36)) and less retinal arteriolar dilatation (difference: - 0.74% (- 1.22; - 0.25)). In women, these associations were numerically in the same direction, but generally not statistically significant (odds ratios: 1.71 (0.90;3.25) and 1.22 (0.75;1.98); differences: 0.29 mu m (- 3.50;4.07) and: - 0.52% (- 1.11;0.08), respectively). Interaction analyses revealed no consistent pattern of sex differences in the associations of either prediabetes or type 2 diabetes or glycemia with microvascular complications or retinal measures. The prevalence of advanced-stage complications was too low for evaluation. Conclusions Our findings show that women with type 2 diabetes are not disproportionately affected by early microvascular complications.Prevention, Population and Disease management (PrePoD)Public Health and primary car

Caco-2 cells secrete two independent classes of lipoproteins with distinct density: effect of the ratio of unsaturated to saturated fatty acid

Polarized Caco-2 cells can synthesize two distinct density classes of lipoproteins, i.e. chylomicron/VLDL (d <1.006 g/ml) or IDL/LDL density (1.009 <d <1.068 g/ml). When saturated fatty acid in the incubation medium is replaced with unsaturated fatty acid, this results in an increase in the basolateral secretion of triglycerides from 18.6 +/- 3.6 nmol/filter (with 0.5 mmol/l 16:0) to 21.4 +/- 6.2, 27.5 +/- 4.8 and 28.9 +/- 5.3 nmol/filter when 10, 20 or 30% of 16:0 were substituted by 18:1. The secretion of IDL/LDL-sized lipoproteins diminished and chylomicron/VLDL secretion increased in proportion to the increase of unsaturated fatty acid in the medium. To gain insight into the relationship between these lipoprotein classes, we determined their secretion at several time intervals (0-4, 4-8 and 22-26 h) after incubation with a fatty acid mixture containing 16:0 and 18:1 in a 9:1 molar ratio (total fatty acid concentration was 0.5 mmol/l). Chylomicron/VLDL secretion was detectable immediately upon the start of the incubation and persisted during all intervals. In contrast, IDL/LDL density lipoproteins were first detectable in the 4-8 h time interval and their secretion was highest in the final phase of the incubation (22-26 h). We conclude that Caco-2 cells secrete two distinct density classes of lipoproteins that show no precursor-product relation