Search results for "PORIN"
showing 10 items of 260 documents
Randomised clinical trial: alisporivir combined with peginterferon and ribavirin in treatment-naïve patients with chronic HCV genotype 1 infection (E…
2015
Summary Background Alisporivir (ALV) is an oral, host-targeting agent with pangenotypic anti-hepatitis C virus (HCV) activity and a high barrier to resistance. Aim To evaluate efficacy and safety of ALV plus peginterferon-α2a and ribavirin (PR) in treatment-naive patients with chronic HCV genotype 1 infection. Methods Double-blind, randomised, placebo-controlled, Phase 3 study evaluating ALV 600 mg once daily [response-guided therapy (RGT) for 24 or 48 weeks or 48 weeks fixed duration] or ALV 400 mg twice daily RGT with PR, compared to PR alone. Following a Food and Drug Administration partial clinical hold, ALV/placebo was discontinued and patients completed treatment with PR only. At that…
First Evidence for a Crosstalk Between Mitochondrial and NADPH Oxidase-Derived Reactive Oxygen Species in Nitroglycerin-Triggered Vascular Dysfunction
2008
Chronic nitroglycerin treatment results in development of nitrate tolerance associated with endothelial dysfunction (ED). We sought to clarify how mitochondria- and NADPH oxidase (Nox)-derived reactive oxygen species (ROS) contribute to nitrate tolerance and nitroglycerin-induced ED. Nitrate tolerance was induced by nitroglycerin infusion in male Wistar rats (100 microg/h/4 day) and in C57/Bl6, p47(phox/) and gp91(phox/) mice (50 microg/h/4 day). Protein and mRNA expression of Nox subunits were unaltered by chronic nitroglycerin treatment. Oxidative stress was determined in vascular rings and mitochondrial fractions of nitroglycerin-treated animals by L-012 enhanced chemiluminescence, revea…
Synaptic vesicle alterations in rod photoreceptors of synaptophysin-deficient mice.
2001
Abstract The abundance of the integral membrane protein synaptophysin in synaptic vesicles and its multiple possible functional contributions to transmitter exocytosis and synaptic vesicle formation stand in sharp contrast to the observed lack of defects in synaptophysin knockout mice. Assuming that deficiencies are compensated by the often coexpressed synaptophysin isoform synaptoporin, we now show that retinal rod photoreceptors, which do not synthesize synaptoporin either in wild-type or in knockout mice, are affected by the loss of synaptophysin. Multiple pale-appearing photoreceptors, as seen by electron microscopy, possess reduced cytoplasmic electron density, swollen mitochondria, an…
Determinants of enhanced thromboxane biosynthesis in renal transplantation
2001
Determinants of enhanced thromboxane biosynthesis in renal transplantation.BackgroundDespite great improvement in patient and graft survival, the long-term morbidity and mortality in renal transplant recipients (RTRs) are still significant, with a high incidence of cardiovascular disease-related deaths.MethodsWe investigated thromboxane (TXA2) biosynthesis and endothelial and coagulative activation in 65 patients who received a renal transplant.ResultsThe rate of TXA2 biosynthesis (urinary 11-dehydro-TXB2 excretion largely reflects platelet TXA2 production in vivo) was significantly (P < 0.0001) higher in RTRs than in healthy subjects. Plasma von Willebrand factor (vWF) and thrombin-antithr…
The GENDER ATTENTION Observational Study: Gender and Hormonal Status Differences in the Incidence of Adverse Events During Cyclosporine Treatment in …
2017
Introduction: Female sex has been shown to be a risk factor for the development of adverse drug reactions; however, this has not been studied for cyclosporine (CsA). The aim of this study was to investigate, in Italian dermatological practice, the influence of gender and menopause and related hormones on the incidence of adverse events (AEs) during CsA treatment in psoriatic patients. Methods: Multicenter, prospective, observational study conducted from May 2011 to June 2013. Patients with plaque psoriasis, undergoing a new CsA administration course, or about to start it, were enrolled in the outpatient clinics of Italian dermatological centers. During the 2–6 months of study duration, pati…
Intestinal transport of cefuroxime axetil in rats: absorption and hydrolysis processes.
2002
Studies were performed using three cefuroxime axetil solutions (11.8, 118 and 200 microM) in three selected intestinal segments and one cefuroxime axetil solution (118 microM) in colon of anaesthetized rats. First-order absorption rate pseudoconstants, k(ap) and effective permeability coefficients, P(eff), were calculated in each set. Absorption of cefuroxime axetil can apparently be described as a carrier-mediated transport, which obeys Michaelis-Menten and first order kinetics in the proximal segment of the small intestine and a passive diffusion mechanism in the mean and distal segments. The absorption kinetic parameters for cefuroxime axetil were obtained: Vm=0.613 (0.440) microM min-1;…
Role of calcineurin in Ca2+-induced release of catecholamines and neuropeptides
1998
Neurotransmission requires rapid docking, fusion, and recycling of neurotransmitter vesicles. Several of the proteins involved in this complex Ca2+-regulated mechanism have been identified as substrates for protein kinases and phosphatases, e.g., the synapsins, synaptotagmin, rabphilin3A, synaptobrevin, munc18, MARCKS, dynamin I, and B-50/GAP-43. So far most attention has focused on the role of kinases in the release processes, but recent evidence indicates that phosphatases may be as important. Therefore, we investigated the role of the Ca2+/calmodulin-dependent protein phosphatase calcineurin in exocytosis and subsequent vesicle recycling. Calcineurin-neutralizing antibodies, which blocke…
Repression of the nuclear receptor small heterodimer partner by steatotic drugs and in advanced nonalcoholic fatty liver disease.
2015
The small heterodimer partner (SHP) (NR0B2) is an atypical nuclear receptor that lacks a DNA-binding domain. It interacts with and inhibits many transcription factors, affecting key metabolic processes, including bile acid, cholesterol, fatty acid, and drug metabolism. Our aim was to determine the influence of steatotic drugs and nonalcoholic fatty liver disease (NAFLD) on SHP expression and investigate the potential mechanisms. SHP was found to be repressed by steatotic drugs (valproate, doxycycline, tetracycline, and cyclosporin A) in cultured hepatic cells and the livers of different animal models of NAFLD: iatrogenic (tetracycline-treated rats), genetic (glycine N-methyltransferase-defi…
Treatment of Duchenne muscular dystrophy with ciclosporin A: a randomised, double-blind, placebo-controlled multicentre trial.
2010
Summary Background Duchenne muscular dystrophy is a rare X-linked progressive disease characterised by loss of ambulation at about age 10 years, with death in early adulthood due to respiratory and cardiac insufficiency. Steroids are effective at slowing the progression of muscle weakness; however, their use is limited by side-effects, prompting the search for alternatives. We assessed the effect of ciclosporin A as monotherapy and in combination with intermittent prednisone for the treatment of ambulant patients with this disorder. Methods Our study was a parallel-group, placebo-controlled, double-blind, multicentre trial at trial sites of the German muscular dystrophy network, MD-NET, ove…
Reversal of Endothelial Nitric Oxide Synthase Uncoupling and Up-Regulation of Endothelial Nitric Oxide Synthase Expression Lowers Blood Pressure in H…
2006
Objectives We sought to examine the hypothesis that a pharmacologic up-regulation of endothelial nitric oxide synthase (eNOS) combined with a reversal of eNOS uncoupling provides a protective effect against cardiovascular disease. Background Many cardiovascular diseases are associated with oxidant stress involving protein kinase C (PKC) and uncoupling of eNOS. Methods Messenger ribonucleic acid (mRNA) expression was analyzed with RNase protection assay or quantitative real-time polymerase chain reaction, vascular nitric oxide (NO) with spin trapping, and reactive oxygen species (ROS) with dihydroethidium fluorescence. Results Aortas of spontaneously hypertensive rats (SHR) showed an elevate…