Search results for "imidazoles"
showing 10 items of 272 documents
Sofosbuvir plus daclatasvir with or without ribavirin is safe and effective for post-transplant hepatitis C recurrence and severe fibrosis and cirrho…
2018
Background: In 2012, an Italian Named Patient Program began for hepatitis C virus (HCV)-infected liver transplant (LT) recipients with advanced fibrosis, before approval of direct antiviral agents (DAA), to benefit severely ill patients. The aim of this “real-life” study was to assess treatment efficacy and safety with an extended course of daclatasvir (DCV) plus sofosbuvir (SOF) with or without ribavirin (RBV). Methods: All HCV LT recipients with severe fibrosis in 15 Italian transplant centers were treated with DCV+SOF±RBV for 24 weeks; sustained virological response was assessed at 12 weeks post-treatment (SVR12). Results: Eighty-seven patients were enrolled (75.9% males, mean age 58.4 ±…
Targeted Repolarization of Tumor‐Associated Macrophages via Imidazoquinoline‐Linked Nanobodies
2021
Abstract Tumor‐associated macrophages (TAMs) promote the immune suppressive microenvironment inside tumors and are, therefore, considered as a promising target for the next generation of cancer immunotherapies. To repolarize their phenotype into a tumoricidal state, the Toll‐like receptor 7/8 agonist imidazoquinoline IMDQ is site‐specifically and quantitatively coupled to single chain antibody fragments, so‐called nanobodies, targeting the macrophage mannose receptor (MMR) on TAMs. Intravenous injection of these conjugates result in a tumor‐ and cell‐specific delivery of IMDQ into MMRhigh TAMs, causing a significant decline in tumor growth. This is accompanied by a repolarization of TAMs to…
PD123319, angiotensin II type II receptor antagonist, inhibits oxidative stress and inflammation in 2, 4-dinitrobenzene sulfonic acid-induced colitis…
2019
Angiotensin II, the main effector of renin angiotensin system, plays an important role in the inflammatory process and most of its effects are mediated through the AT1 receptor activation. However, the knowledge about the AT2 receptor involvement in this process is still evolving. We previously found that in an experimental model of colitis, AT2 receptor activation can contribute to the impairment of the muscle contractility in vitro in the course of inflammation. Here, we investigated the potential alleviating effects of the in vivo treatment of PD123319 (1-[[4-(Dimethylamino)-3-methylphenyl]methyl]-5-(diphenylacetyl)-4,5,6,7- tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid ditriflu…
Overall survival in patients with BRAF-mutant melanoma receiving encorafenib plus binimetinib versus vemurafenib or encorafenib (COLUMBUS): a multice…
2018
Summary Background Encorafenib plus binimetinib and encorafenib alone improved progression-free survival compared with vemurafenib in patients with BRAF V600 -mutant melanoma in the COLUMBUS trial. Here, we report the results of the secondary endpoint of overall survival. Methods COLUMBUS was a two-part, randomised, open-label, phase 3 study done at 162 hospitals in 28 countries. Eligible patients were aged at least 18 years with histologically confirmed, locally advanced, unresectable, or metastatic cutaneous melanoma, or unknown primary melanoma, BRAF V600E or BRAF V600K mutation, an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and were treatment naive or had pr…
Real-life use of elbasvir/grazoprevir in adults and elderly patients: a prospective evaluation of comedications used in the PITER cohort.
2021
Background In patients treated for HCV infection, potential drug–drug interactions (DDIs) can occur among direct-acting antiviral drugs (DAAs) and comedications used. The real-life effectiveness and safety of elbasvir/grazoprevir (ELB/GZR) among co-medicated HCV patients was evaluated. Methods We prospectively evaluated consecutive patients from 15 clinical centres participating in PITER who were treated with ELB/GZR and had been followed for at least 12 weeks after treatment. Data were prospectively collected on the use of comedications (including discontinuation, dose modification and addition of drugs) and potential DDIs with DAAs. Results Of the 356 patients with at least 12-week post-t…
Effectiveness and safety of glecaprevir/pibrentasvir in chronic hepatitis C patients: Results of the Italian cohort of a post-marketing observational…
2021
Abstract Background and Aims The MARS post-marketing, observational study evaluates glecaprevir/pibrentasvir in a large population of Italian patients who are infected with HCV. Patients and Methods Achievement of SVR12 was the primary endpoint in the overall population and by subpopulations of interest (treatment-naive and treatment-experienced patients, subjects infected with different HCV genotype/sub-genotype, cirrhotic and non-cirrhotic patients, patients with different severity of fibrosis, patients with an APRI score ≥1, subjects with comorbidities, HIV-coinfected patients, elderly patients and people who use drugs). Safety and quality of life (assessed by SF-36 and Work Productivity…
Role of angiotensin II in arterial pressure and renal hemodynamics in rats with altered renal development: age- and sex-dependent differences
2012
Numerous studies have demonstrated that angiotensin II (ANG II) is involved in hypertension and renal changes occurring as a consequence of an adverse event during renal development. However, it was unknown whether this involvement is sex and age dependent. This study examines whether the increments in arterial pressure (AP) and in the renal sensitivity to ANG II are sex and age dependent in rats with altered renal development. It also evaluates whether the ANG II effects are accompanied by increments in AT1 receptors and oxidative stress. Experiments were performed in 3- to 4- and 10- to 11-mo-old rats treated with vehicle or an AT1 receptor antagonist (ARAnp) during the nephrogenic perio…
Benzimidazolones and renzapride facilitate acetylcholine release from guinea-pig myenteric plexus via 5-HT4 receptors
1995
The effects of the 5-HT4 receptor agonists BIMU 8, BIMU 1, renzapride and of the 5-HT1p receptor agonist 5-hydroxyindalpine on basal and electrically evoked outflow of tritium were studied in guinea-pig longitudinal muscle myenteric plexus preparations preincubated with [3H]choline. Muscle contractions were recorded simultaneously. BIMU 8 caused a calcium dependent and tetrodotoxin sensitive increase in basal [3H]outflow that was assumed to represent release of [3H]acetylcholine. In addition, BIMU 8 enhanced the release of [3H]acetylcholine and twitch contractions evoked by submaximal electrical stimulation. Ondansetron (1 μmol/l) did not change the effects of BIMU 8, but DAU 6285 and tropi…
Anti-anhedonic actions of the novel serotonergic agent flibanserin, a potential rapidly-acting antidepressant
1998
Chronic exposure to mild unpredictable stress has previously been found to depress the consumption of palatable sweet solutions and to block the formation of conditioned place preferences; these effects are reversed by chronic treatment with tricyclic or atypical antidepressant drugs. The present study was designed to evaluate the antidepressant-like activity in this model of flibaserin (BIMT-17), a novel serotonergic agent with 5-HT1A receptor agonist and 5-HT2 receptor antagonist properties. Two experiments were conducted, using rats (experiment 1) and mice (experiment 2). In experiment 1, decreases in sucrose intake were seen in rats exposed to chronic mild stress, but the effect was unr…
STIMULATION OF ?1-ADRENOCEPTORS ENHANCES ELECTRICALLY EVOKED [3H]-ACETYLCHOLINE RELEASE FROM RAT PHRENIC NERVE
1990
1. The effects of isoprenaline, noradrenaline and fenoterol on the electrically evoked release of [3H]-acetylcholine from the rat phrenic nerve were investigated. 2. Isoprenaline (0.1 mumol/L) and noradrenaline (1 mumol/L) enhanced evoked [3H]-acetylcholine release by about 90%, an effect which was abolished by CGP 20712A (0.1 mumol/L), a specific antagonist at beta 1-adrenoceptors. Noradrenaline still enhanced [3H]-acetylcholine release in the presence of phentolamine (1 mumol/L). 3. The enhancing effect of both isoprenaline and noradrenaline decreased at prolonged exposure times (24-32 min). A pre-exposure of the tissue to a low concentration (0.01 mumol/L) of isoprenaline prevented the e…