Search results for "thiazolidinediones"
showing 10 items of 33 documents
Effects of PPARγ agonists on the expression of leptin and vascular endothelial growth factor in breast cancer cells.
2013
The obesity hormone leptin has been implicated in breast cancer development. Breast cancer cells express the leptin receptor and are able to synthesize leptin in response to obesity-related stimuli. Furthermore, leptin is a positive regulator of vascular endothelial growth factor (VEGF) and high levels of both proteins are associated with worse prognosis in breast cancer patients. Peroxisome proliferator-activated receptor γ (PPARγ) ligands are therapeutic agents used in patient with Type 2 diabetes and obesity which have recently been studied for their potential anti-tumor effect. Here, we studied if these compounds, ciglitazone and GW1929, can affect the expression of leptin and VEGF in b…
Fibrogenesis assessed by serological type III collagen formation identifies patients with progressive liver fibrosis and responders to a potential an…
2016
There are no approved treatments for liver fibrosis. To aid development of antifibrotic therapies, noninvasive biomarkers that can identify patients with progressive fibrosis and that permit monitoring of the response to antifibrotic therapy are much needed. Samples from a phase II antifibrotic trial of the glitazone farglitazar in patients with advanced hepatitis C, with matched follow-up liver biopsies, and from a phase III study of balaglitazone in patients with late-stage Type 2 diabetes (BALLET study) were analyzed for serological Pro-C3 levels in conjunction with other disease parameters. In the farglitazar study, a predefined cutoff value for Pro-C3 as a selection criterion led to t…
Fluorescent benzofurazan-cholic acid conjugates for in vitro assessment of bile acid uptake and its modulation by drugs.
2009
One of the most common mechanisms of hepatotoxicity is drug-induced cholestasis. Hence, new approaches for screening the cholestatic potential of drug candidates are desirable. In this context, we describe herein the use of synthetic 4-nitrobenzo-2-oxa-1,3-diazole (NBD) fluorescent conjugates of cholic acid (ChA) at positions 3alpha, 3beta, 7alpha, and 7beta for in vitro assessment of bile acid uptake. All the conjugates show a strong absorption band between 400 and 550 nm and have a fluorescence quantum yield of approximately 0.45, with an emission maximum centered at approximately 530 nm. After their photophysical characterization, 3alpha-, 3beta-, 7alpha-, and 7beta-NBD-ChA were used to …
Effects on the incidence of cardiovascular events of the addition of pioglitazone versus sulfonylureas in patients with type 2 diabetes inadequately …
2017
Background The best treatment option for patients with type 2 diabetes in whom treatment with metformin alone fails to achieve adequate glycaemic control is debated. We aimed to compare the long-term effects of pioglitazone versus sulfonylureas, given in addition to metformin, on cardiovascular events in patients with type 2 diabetes. Methods TOSCA.IT was a multicentre, randomised, pragmatic clinical trial, in which patients aged 50â75 years with type 2 diabetes inadequately controlled with metformin monotherapy (2â3 g per day) were recruited from 57 diabetes clinics in Italy. Patients were randomly assigned (1:1), by permuted blocks randomisation (block size 10), stratified by site and…
Investigation of the vascular and pleiotropic effects of atorvastatin and pioglitazone in a population at high cardiovascular risk.
2008
We investigated the effect of atorvastatin monotherapy and combined treatment with atorvastatin and pioglitazone on intima-media thickness, vascular function and the cardiovascular risk profile. In all, 148 patients (76 male, 72 female; aged 61.4±6.5 years; body mass index [BMI] 29.2±4.1 kg/m2; mean±SD) with increased cardiovascular (CV) risk factors were randomised. Intima-media thickness (IMT), the augmentation index (Aix@75), the microvascular response to acetylcholine (LDF), lipid status, and plasma levels of intact proinsulin, adiponectin, interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9), sCD40L, P-selectin, tissue plasminogen activator …
Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-l…
2009
Udgivelsesdato: 2009-Jun-20 BACKGROUND: Rosiglitazone is an insulin sensitiser used in combination with metformin, a sulfonylurea, or both, for lowering blood glucose in people with type 2 diabetes. We assessed cardiovascular outcomes after addition of rosiglitazone to either metformin or sulfonylurea compared with the combination of the two over 5-7 years of follow-up. We also assessed comparative safety. METHODS: In a multicentre, open-label trial, 4447 patients with type 2 diabetes on metformin or sulfonylurea monotherapy with mean haemoglobin A(1c) (HbA(1c)) of 7.9% were randomly assigned to addition of rosiglitazone (n=2220) or to a combination of metformin and sulfonylurea (active con…
Effects of Rosiglitazone on Fasting and Postprandial Low- and High-Density Lipoproteins Size and Subclasses in Type 2 Diabetes
2010
Rosiglitazone may increase cardiovascular risk in patients with type 2 diabetes. Yet, its effects on atherogenic dyslipidemia are still not fully elucidated. In a prospective open-label study rosiglitazone (4 mg/day for 12 weeks) was added to a maximum of 2 oral antidiabetic drugs in 18 diabetic patients. We evaluated the effects on plasma lipids before and after an oral fat load. The size and subclasses of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) were also determined (by gradient gel electrophoresis). Rosiglitazone improved glycosylated hemoglobin ([HbA1c] P = .0023), without significant effects on fasting and postprandial plasma lipids. Fasting LDL size increased …
Should low high-density lipoprotein cholesterol (HDL-C) be treated?
2014
The first observations linking a low serum level of HDL-C to increased risk for cardiovascular disease were made over 50 years ago. High serum levels of HDL-C appear to protect against the development of atherosclerotic disease, while low serum levels of this lipoprotein are among the most important predictors of atherosclerotic disease in both men and women and people of all racial and ethnic groups throughout the world. It has long been assumed that therapeutic interventions targeted at raising HDL-C levels would lower risk for such cardiovascular events as myocardial infarction, ischemic stroke, and death. Even after five decades of intensive investigation, evidence to support this assum…
Pioglitazone Reduces Secondary Brain Damage after Experimental Brain Trauma by PPAR-γ-Independent Mechanisms
2011
Inflammatory and ischemic processes contribute to the development of secondary brain damage after mechanical brain injury. Recent data suggest that thiazolidinediones (TZDs), a class of drugs approved for the treatment of non-insulin-dependent diabetes mellitus, effectively reduces inflammation and brain lesion by stimulation of the peroxisome proliferator-activated receptor-γ (PPAR-γ). The present study investigates the influence of the TZD pioglitazone and rosiglitazone on inflammation and secondary brain damage after experimental traumatic brain injury (TBI). A controlled cortical impact (CCI) injury was induced in male C57BL/6 mice to investigate following endpoints: (1) mRNA expression…
Comparative effects of rosiglitazone and pioglitazone on fasting and postprandial low-density lipoprotein size and subclasses in patients with Type 2…
2008
To assess the effects of pioglitazone and rosiglitazone on fasting and postprandial low-density lipoprotein (LDL) size and subclasses in patients with Type 2 diabetes.Nine Type 2 diabetic patients (age 61 +/- 10 years, body mass index 30 +/- 5 kg/m(2), glycosylated hemoglobin [HbA1c] 7.5 +/- 0.5%) were randomized in a crossover trial to rosiglitazone 4 mg b.i.d. or pioglitazone 45 mg/day for 12 weeks with an 8-week wash-out period. LDL size and subclasses were determined by non-denaturing polyacrylamide gradient gel electrophoresis. A standardized breakfast was served and variables were assessed after 3 and 6 h.HbA1c, insulin sensitivity (as assessed by the homeostasis model assessment) and…