Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: fundamentals of care for uveitis (focus) initiative

Topic: An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. Clinical Relevance: The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. Methods: An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic reviewof the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE,CINAHL,SCOPUS,BIOSIS, andWeb of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review.Atotal of 44 globally representativegroupmembersmet in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. Results: In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations. Pharmacoeconomic considerations were not addressed. Conclusions: Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents

The effects of alpha lipoic acid on liver cells damages and apoptosis induced by polyunsaturated fatty acids

Öze

Effect of glucagon-like peptide-1(7-36) and exendin-4 on the vascular reactivity in streptozotocin/nicotinamide-induced diabetic rats

We investigated the vascular effects of glucagon-like peptide-1 (GLP-1) and Exendin-4 in type 2 diabetic rat aortae. Studies were performed in a normal control group (NC) (0.2 ml i. p. saline, n = 10), streptozotocin (STZ)/ nicotinamide diabetic control group ( DC) ( a single dose of 80 mg/kg STZ i. p. injection 15 min after administration of 230 mg/kg nicotinamide i. p.), GLP-1 (GLPC) control group ( 1 mu g/kg twice daily i. p. for 1 month, n = 10), Exendin-4 control group (EXC) ( 0.1 mu g/kg twice daily i. p. for 1 month, n = 10), GLP-1-treated diabetic group (GLPT) ( 1 mu g/kg twice daily i. p. for 1 month, n = 10), and Exendin-4-treated diabetic group (EXT) ( 0.1 mu g/kg twice daily i. p. for 1 month, n = 10). One month of GLP-1 and Exendin-4 treatment significantly decreased the blood glucose levels of diabetic rats ( 113 +/- 2 mg/dl, p < 0.001, and 117 +/- 1 mg/ dl, p < 0.001, respectively versus 181 +/- 9 mg/ dl in the DC group). Sensitivity (pD(2)) and maximum response (% Max. Relax) of acetylcholine-stimulated relaxations in the DC group (pD(2) : 6.73 +/- 0.12 and 55 +/- 6, respectively) were decreased compared with the nondiabetic NC group (pD(2) : 7.41 +/- 0.25, p < 0.05, and 87 +/- 4, p < 0.01). Treating diabetic rats with GLP-1, pD(2) values and with Exendin-4, Max. Relax % values of aortic strips to acetylcholine returned to near non-diabetic NC values (pD(2) : 7.47 +/- 0.15, p < 0.05, and 87 +/- 3, p < 0.01, respectively). Maximal contractile responses (E-max) to noradrenaline in aortic strips from the diabetic DC group (341 +/- 27 mg tension/mg wet weight) were significantly decreased compared with the non-diabetic NC ( 540 +/- 66 mg tension/mg wet weight, p < 0.001) and the GLPT group ( 490 +/- 25 mg tension/ mg wet weight, p < 0.05). There were no significant differences in pD(2) values of aortic strips to noradrenaline from all groups. E-max to KCl in aortic strips from the DC group ( 247 +/- 10 mg tension/ mg wet weight, p < 0.01) was significantly decreased compared with non-diabetic NC group ( 327 +/- 26 mg tension/ mg wet weight). Treating diabetic rats with GLP-1 (GLPT), E-max values of aortic strips to KCl returned to near non-diabetic NC values ( 271 +/- 12 mg tension/ mg wet weight). GLP-1 and ( partially) Exendin-4 treatment could improve the increased blood glucose level and normalize the altered vascular tone in type 2 diabetic rats. Copyright (C) 2005 S. Karger AG, Basel

Investigation of MTHFR gene C677T polymorphism in cardiac syndrome X patients

BackgroundDefinition of Cardiac Syndrome X (CSX) refers to groups of patients with positive exercise stress test and normal epicardial coronary arteries on coronary angiography accompanied by chest pain. Although the etiology of CSX is not completely understood, there is a common consensus that its pathophysiology may be associated with endothelial dysfunction resulting in impaired coronary flow. Some polymorphisms observed on the MTHFR gene cause inactivation of the MTHFR enzyme, leading to hyperhomocysteinemia and homocysteinuria, which are prominent risk factors of cardiovascular and cerebrovascular diseases. It was aimed to explain the association of the endothelial dysfunction, which is thought to play a role in the pathophysiology of CSX, with C677T polymorphism on MTHFR gene based on genetic basis

Plasma Betatrophin Levels of Subjects Classified with Normal, Impaired, and Diabetic Glucose Tolerance, and Subjects with Impaired Fasting Glucose

This study was aimed to investigate whether betatrophin shows glucose intolerance or not. To access the plasma betatrophin levels after basal and glucose load, groups were classified as normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetic glucose tolerance (DGT) according to WHO 2012 criteria. An oral glucose tolerance test was performed on age-matched subjects (n = 220) with a body mass index (BMI) < 27 kg/m(2). Subjects were categorized as normoglycemic (n = 55), IFG (n = 50), IGT (n = 60), and DM (n = 55) according to the WHO criteria. Baseline betatrophin levels in DGT are significantly higher than in NGT (p < 0.005), IFG (p < 0.004), and IGT (p < 0.001). Male subjects have significantly higher betatrophin levels than female subjects (p < 0.01). In DGT, betatrophin of male subjects was found to be significantly higher than the betatrophin of male subjects in NGT (p < 0.04), IFG (p < 0.01), and IGT (p < 0.01). Significant relationship between betatrophin and both ages and HbA1c in all groups were observed. When ages were accepted as an independent factor, significant correlation between betatrophin and ages were found. Betatrophin is increased and associated with age and HbA1c in DGT. Males had higher betatrophin levels compared with females in DGT group. As no obvious betatrophin deficiency to substitute in IFG and IGT individuals were observed, betatrophin levels appeared to be related to the pathogenesis of the diabetic stages rather than prediabetic stages

Effects of omega-3 polyunsaturated fatty acid supplementation on serum fetuin-A levels in type 2 diabetic patients

Fetuin-A is an endogenous inhibitor of the insulin-stimulated insulin receptor tyrosine kinase recently shown that high levels of circulating fetuin-A are associated with insulin resistance in humans suggesting that fetuin-A may represent a novel mechanism involved in the pathophysiology of type 2 diabetes (T2DM). Dietary omega-3 polyunsaturated fatty acids (n-3 PUFAs) are known to reduce triglyceride levels, but their impact on glycemic control are not well known. The aim of this study to determine the effects of omega-3 PUFA supplementation on fetuin-A and glycemic control in patients with type 2 diabetes mellitus. 40 T2DM patients (17 males/23 females; aged 39-65 years) were included in the study. Serum fetuin-A levels and metabolic and biochemical profiles were measured before (baseline) and two months after n-3 PUFA supplementations (1.2 g/day). Serum fetuin-A levels were measured by enzyme-linked immunosorbent assay. Our results indicated that serum fetuin-A, fasting glucose, HbA1c and triglyceride levels were significantly decreased after supplementation (P<0.02, P<0.001, P<0.02 and P<0.01, respectively). At baseline, serum fetuin-A levels were correlated with HbA1c (r:-0.391, P<0.04). A significant positive correlation between fetuin-A and both triglycerides (r: 0.343, P<0.05) and total cholesterol (r: 0.330, P<0.05) and negative correlation between fetuin-A and fasting glucose (r: -0.405, P<0.01) were found after the supplementations. When performed multiply regression analysis, we found that serum fetuin-a levels were related with triglyceride levels (r: 0.351, P<0.01) at baseline and HbA1c levels (r: 0.344, P<0.04) after the supplementation. Based on the results, it thought that omega-3 PUFA intake decreases serum fetuin-A levels and serum fetuin-A is associated with plasma lipids and glycemic controls in type 2 diabetic patients. Further studies are required to resolve the question

The in vitro Effects of Iloprost with Other Vasodilators on the Human Internal Thoracic Artery

Purpose: We aimed (a) to analyze the effects of iloprost as a vasodilator on the human internal thoracic artery (ITA) and (b) to compare these effects with the effects of other vasodilators now being used in the clinic