Search results for "antagonists"
showing 10 items of 1346 documents
A randomized, placebo-controlled trial of cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis
2018
The aim of this study was to evaluate cenicriviroc (CVC), a dual antagonist of C-C chemokine receptor types 2 and 5, for treatment of nonalcoholic steatohepatitis (NASH) with liver fibrosis. A randomized, double-blind, multinational phase 2b study enrolled subjects with NASH, a nonalcoholic fatty liver disease activity score [NAS] ≥4, and liver fibrosis (stages 1-3, NASH Clinical Research Network) at 81 clinical sites. Subjects (N = 289) were randomly assigned CVC 150 mg or placebo. Primary outcome was ≥2-point improvement in NAS and no worsening of fibrosis at year 1. Key secondary outcomes were: resolution of steatohepatitis and no worsening of fibrosis; improvement in fibrosis by ≥1 stag…
Molecular mechanisms underlying the neuroprotective role of atrial natriuretic peptide in experimental acute ischemic stroke
2018
Abstract Along with its role in regulating blood pressure and fluid homeostasis, the natriuretic peptide system could be also part of an endogenous protective mechanism against brain damage. We aimed to assess the possibility that exogenous atrial natriuretic peptide (ANP) could protect against acute ischemic stroke, as well as the molecular mechanisms involved. Three groups of rats subjected to transient middle cerebral artery occlusion (tMCAO, intraluminal filament technique, 60 min) received intracerebroventricular vehicle, low-dose ANP (0.5 nmol) or high-dose ANP (2.5 nmol), at 30 min reperfusion. Neurofunctional condition, and brain infarct and edema volumes were measured at 24 h after…
The maternal hormone in the male brain: Sexually dimorphic distribution of prolactin signalling in the mouse brain.
2018
Research of the central actions of prolactin is highly focused on females, but this hormone has also documented roles in male physiology and behaviour. Here, we provide the first description of the pattern of prolactin-derived signalling in the male mouse brain, employing the immunostaining of phosphorylated signal transducer and activator of transcription 5 (pSTAT5) after exogenous prolactin administration. Next, we explore possible sexually dimorphic differences by comparing pSTAT5 immunoreactivity in prolactin-supplemented males and females. We also assess the role of testosterone in the regulation of central prolactin signalling in males by comparing intact with castrated prolactin-supp…
Brain histamine depletion enhances the behavioural sequences complexity of mice tested in the open-field: Partial reversal effect of the dopamine D2/…
2017
Markers of histaminergic dysregulation were found in several neuropsychiatric disorders characterized by repetitive behaviours, thoughts and stereotypies. We analysed the effect of acute histamine depletion by means of i. c.v. injections of alpha-fluoromethylhistidine, a blocker of histidine decarboxylase, on the temporal organization of motor sequences of CD1 mice behaviour in the open-field test. An ethogram encompassing 9 behavioural components was employed. Durations and frequencies were only slightly affected by treatments. However, as revealed by multivariate t-pattern analysis, histamine depletion was associated with a striking increase in the number of behavioural patterns. We found…
A Predictive Model of the Prevalence of Delirium in Elderly Subjects Admitted to Nursing Homes.
2017
INTRODUCTION Delirium is common in geriatric patients admitted to nursing homes, with an incidence of 22-79% among long-term residents. AIM To establish a predictive model of the risk of delirium episodes in a sample of elderly people living in nursing homes. MATERIAL AND METHODS A retrospective, cross-sectional case-control study covering a period of 12 consecutive months (April 2014 - March 2015) was carried out. The included cases had suffered at least one episode of delirium during the study period. Sociodemographic and clinical variables as well as risk factors predisposing to or triggering episodes of delirium were recorded. RESULTS A total of 193 cases and 123 controls were recruited…
Pistachio Consumption Alleviates Inflammation and Improves Gut Microbiota Composition in Mice Fed a High-Fat Diet.
2019
High-fat diet (HFD) induces inflammation and microbial dysbiosis, which are components of the metabolic syndrome. Nutritional strategies can be a valid tool to prevent metabolic and inflammatory diseases. The aim of the present study was to evaluate if the chronic intake of pistachio prevents obesity-associated inflammation and dysbiosis in HFD-fed mice. Three groups of male mice (four weeks old
Moving Towards Precision Urologic Oncology: Targeting Enzalutamide-resistant Prostate Cancer and Mutated Forms of the Androgen Receptor Using the Nov…
2017
Abstract Darolutamide (ODM-201) is a novel androgen receptor (AR) antagonist with a chemical structure distinctly different from currently approved AR antagonists that targets both wild-type and mutated ligand binding domain variants to inhibit AR nuclear translocation. Here, we evaluate the activity of darolutamide in enzalutamide-resistant castration resistant prostate cancer (CRPC) as well as in AR mutants detected in patients after treatment with enzalutamide, abiraterone, or bicalutamide. Darolutamide significantly inhibited cell growth and AR transcriptional activity in enzalutamide-resistant MR49F cells in vitro, and led to decreased tumor volume and serum prostate-specific antigen l…
RAAS inhibitors are not associated with mortality in COVID-19 patients: Findings from an observational multicenter study in Italy and a meta-analysis…
2020
Abstract Objective The hypothesis that been set forward that use of Renin Angiotensin Aldosterone System (RAAS) inhibitors is associated with COVID−19 severity. We set-up a multicenter Italian collaboration (CORIST Project, ClinicalTrials.gov ID: NCT04318418 ) to retrospectively investigate the relationship between RAAS inhibitors and COVID−19 in-hospital mortality. We also carried out an updated meta-analysis on the relevant studies. Methods We analyzed 4069 unselected patients with laboratory-confirmed SARS-CoV-2 infection and hospitalized in 34 clinical centers in Italy from February 19, 2020 to May 23, 2020. The primary end-point in a time-to event analysis was in-hospital death, compar…
The clinical relevance of adiposity when assessing muscle health in men treated with androgen deprivation for prostate cancer
2019
Background: Androgen deprivation therapy (ADT) for prostate cancer (PCa) may prospectively decrease absolute lean mass (LM) and increase absolute fat mass (FM). Given that estimates of LM by dual‐energy X‐ray absorptiometry may be overestimated in obese people, this study examined the influence of adiposity on muscle health in men treated with ADT for PCa. Methods: This cross‐sectional study examined the influence of adiposity on total and appendicular LM (ALM), muscle cross‐sectional (CSA), and muscle strength in 70 men treated with ADT [mean (standard deviation) age, 71 (6) years] for PCa compared with age‐matched PCa (n = 52) and healthy controls (n = 70). Total body LM, FM and ALM, and …
Ticagrelor, but not clopidogrel, reduces arterial thrombosis via endothelial tissue factor suppression
2017
The P2Y12 antagonist ticagrelor reduces mortality in patients with acute coronary syndrome (ACS), compared with clopidogrel, and the mechanisms underlying this effect are not clearly understood. Arterial thrombosis is the key event in ACS; however, direct vascular effects of either ticagrelor or clopidogrel with focus on arterial thrombosis and its key trigger tissue factor have not been previously investigated.Methods and results: Human aortic endothelial cells were treated with ticagrelor or clopidogrel active metabolite (CAM) and stimulated with tumour necrosis factor-alpha (TNF-α); effects on procoagulant tissue factor (TF) expression and activity, its counter-player TF pathway inhibito…