Alzheimer's disease and type 2 diabetes mellitus: A systematic review of proteomic studies.

Similar to dementia, the risk for developing type 2 diabetes mellitus (T2DM) increases with age, and T2DM also increases the risk for dementia, particularly Alzheimer's disease (AD). Although T2DM is primarily a peripheral disorder and AD is a central nervous system disease, both share some common features as they are chronic and complex diseases, and both show involvement of oxidative stress and inflammation in their progression. These characteristics suggest that T2DM may be associated with AD, which gave rise to a new term, type 3 diabetes (T3DM). In this study, we searched for matching peripheral proteomic biomarkers of AD and T2DM based in a systematic review of the available literature. We identified 17 common biomarkers that were differentially expressed in both patients with AD or T2DM when compared with healthy controls. These biomarkers could provide a useful workflow for screening T2DM patients at risk to develop AD.

Algorithm for predicting low maintenance doses of warfarin using age and polymorphisms in genes CYP2C9 and VKORC1 in Brazilian subjects.

Warfarin exhibits a wide variation in dose requirements. We sought to evaluate the association of polymorphisms CYP2C9*2 (rs1799853), CYP2C9*3 (rs1075910), and VKORC1-G1639A (rs9923231) and nongenetic factors with maintenance doses of warfarin <17.5 mg/week and to create an algorithm to predict drug sensitivity. This is a retrospective cohort study including 312 patients assisted at an anticoagulation clinic in Brazil. The mean age of participants was 60.4 ± 13.5 years and 59.9% were female. The logistic regression model included: age [odds ratio (OR) 1.03, 95% confidence interval (CI) 1.01-1.06], genotype VKORC1 AA (OR 31.61, 95% CI 11.20-100.15) and genotype CYP2C9 2/2, 2/3 or 3/3 (OR 16.48, 95% CI 3.37-81.79). The creation of our algorithm involved warfarin-experienced patients on stable doses, identifying factors associated with drug sensitivity. The validation of this algorithm allows its use in future populations to determine the initial dose distinguishing patients with dose requirements <17.5 mg and reducing time to achieve stable doses.

Pre-eclampsia is associated with reduced resolvin D1 and maresin 1 to leukotriene B4 ratios in the plasma.

PROBLEM: Omega-3 and omega-6 fatty acids can be endogenously converted into mediators with pro-inflammatory (eg, leukotriene B4/LTB4) or anti-inflammatory/pro-resolving activities (eg, resolvin D1/RvD1 and maresin 1/MaR1). Recent data indicate an imbalance of LTB4 and MaR1 levels in pre-eclampsia (PE), but the relative production of these mediators, including RvD1, and the role of these mediators in the disease pathogenesis remain unclear. Therefore, this study aimed to investigate the plasma levels of LTB4, RvD1, and MaR1 in pregnant women with or without PE and non-pregnant controls and their association with clinical/laboratory parameters of PE women. METHOD OF STUDY: LTB4, RvD1, and MaR1 plasma levels were measured by competitive enzyme immunoassay in 19 non-pregnant, 20 normotensive pregnant, and 21 PE women. RESULTS: Plasma concentrations of LTB4 were higher and RvD1 were lower in PE women than in normotensive pregnant women, who presented higher levels of LTB4 and similar levels of RvD1 to non-pregnant women. MaR1 levels did not differ among the groups. Pre-eclampsia women had decreased RvD1/LTB4 and MaR1/LTB4 ratios. Considering only the PE group, positive correlations were observed among all the mediators tested, between LTB4 and white blood cell count and between RvD1 and creatinine levels. However, all lipid mediators correlated negatively with body mass index before pregnancy. LTB4 also correlated negatively with maternal age. CONCLUSION: Our findings suggest that the PE state results in systemic overproduction of LTB4 in relation to RvD1 and MaR1, and that these lipid mediators may be involved with the disease pathogenesis.

Cytokine Signature in End-Stage Renal Disease Patients on Hemodialysis.

Hemodialysis is a modality of blood filtration in which accumulated toxins and water are removed from the body. This treatment is indicated for patients at the end stage of renal disease. Vascular access complications are responsible for 20-25% of all hospitalizations in dialyzed patients. The occurrence of thrombosis in the vascular access is a serious problem that may severely compromise or even make the hemodialysis impossible, which is vital for the patient. The aim of this study was to investigate inflammatory profile in patients undergoing hemodialysis as well as the association between these alterations and vascular access thrombosis. A total of 195 patients undergoing hemodialysis have been evaluated; of which, 149 patients had not experienced vascular access thrombosis (group I) and 46 patients had previously presented this complication (group II). Plasma levels of cytokines including interleukin (IL-) 2, IL-4, IL-5, IL-10, TNF-α, and IFN-γ were measured by cytometric bead array. Our results showed that patients with previous thrombotic events (group II) had higher levels of the IL-2, IL-4, IL-5, and IFN-γ when compared to those in group I. Furthermore, a different cytokine signature was detected in dialyzed patients according to previous occurrences or not of thrombotic events, suggesting that elevated levels of T-helper 1 and T-helper 2 cytokines might, at least in part, contribute to this complication.

Association of Haemostatic and Inflammatory Biomarkers with Nephropathy in Type 1 Diabetes Mellitus.

This study aimed at investigating the association between haemostatic biomarkers, proinflammatory, and anti-inflammatory cytokines with chronic kidney disease in type 1 diabetic patients. Patients were divided into two groups: with nephropathy (albuminuria ≥ 30 mg/g and/or GFR < 60 mL/min/1.73 m(2)), n = 65; and without nephropathy (albuminuria < 30 mg/g and GFR ≥ 60 mL/min/1.73 m(2)), n = 60. INF-γ, IL-6, IL-10, and TNF-α plasma levels were determined by flow cytometry. VWF, ADAMTS13 antigen, and D-Dimer plasma levels were determined by enzyme-linked immunosorbent assay and ADAMTS13 activity was assessed by fluorescence resonance energy transfer assay. Elevated levels of INF-γ, VWF, ADAMTS13 antigen, D-Dimer, and reduced ADAMTS13 activity/antigen ratio were observed in patients with nephropathy as compared to those without nephropathy (P = 0.001, P < 0.001, P < 0.001, P < 0.001, and P < 0.001, resp.). Cytokines and haemostatic biomarkers remained associated with nephropathy after adjustments (use of statin, acetylsalicylic acid, angiotensin converting enzyme inhibitor, and angiotensin antagonist). INF-γ, TNF-α, and IL-10 significantly correlated with haemostatic biomarkers. Inflammatory and hypercoagulability status are associated with nephropathy in type 1 diabetes mellitus and an interrelationship between them may play an important role in pathogenesis of diabetic nephropathy.