Search results for "carbamate"
showing 10 items of 219 documents
The FAAH inhibitor URB597 suppresses hippocampal maximal dentate afterdischarges and restores seizure-induced impairment of short and long-term synap…
2017
Synthetic cannabinoids and phytocannabinoids have been shown to suppress seizures both in humans and experimental models of epilepsy. However, they generally have a detrimental effect on memory and memory-related processes. Here we compared the effect of the inhibition of the endocannabinoid (eCB) degradation versus synthetic CB agonist on limbic seizures induced by maximal dentate activation (MDA) acute kindling. Moreover, we investigated the dentate gyrus (DG) granule cell reactivity and synaptic plasticity in naïve and in MDA-kindled anaesthetised rats. We found that both the fatty acid amide hydrolase (FAAH) inhibitor URB597 and the synthetic cannabinoid agonist WIN55,212-2 displayed AM…
Metabolism of tresperimus by rat aorta semicarbazide-sensitive amine oxidase (SSAO).
2002
Tresperimus (Cellimis), a new immunosuppressive agent, is mainly eliminated in the rat through metabolism, in which the oxidative deamination of the primary amine of the drug plays a major role. We have previously demonstrated in vivo the significant involvement of semicarbazide-sensitive amine oxidase (SSAO) in this reaction. Rat aorta, a tissue with one of the highest specific SSAO activities, was tested as a new in vitro model to elucidate tresperimus metabolism, using a combination of liquid chromatography/mass spectrometry (LC/MS) and high-performance liquid chromatography (HPLC) analyses. The metabolites resulting from the main metabolic pathway of the drug were formed in rat aorta ho…
Therapeutic Potential of Inhibitors of Endocannabinoid Degradation for the Treatment of Stress-Related Hyperalgesia in an Animal Model of Chronic Pain
2014
The occurrence of chronic stress, depression, and anxiety can increase nociception in humans and may facilitate the transition from localized to chronic widespread pain. The mechanisms underlying chronic widespread pain are still unknown, hindering the development of effective pharmacological therapies. Here, we exposed C57BL/6J mice to chronic unpredictable stress (CUS) to investigate how persistent stress affects nociception. Next, mice were treated with multiple intramuscular nerve growth factor (NGF) injections, which induced chronic widespread nociception. Thus, combination of CUS and NGF served as a model where psychophysiological impairment coexists with long-lasting hyperalgesia. We…
Reduced anxiety-like behaviour induced by genetic and pharmacological inhibition of the endocannabinoid-degrading enzyme fatty acid amide hydrolase (…
2007
Anandamide and 2-arachidonoyl glycerol, referred to as endocannabinoids (eCBs), are the endogenous agonists for the cannabinoid receptor type 1 (CB1). Several pieces of evidence support a role for eCBs in the attenuation of anxiety-related behaviours, although the precise mechanism has remained uncertain. The fatty acid amid hydrolase (FAAH), an enzyme responsible for the degradation of eCBs, has emerged as a promising target for anxiety-related disorders, since FAAH inhibitors are able to increase the levels of anandamide and thereby induce anxiolytic-like effects in rodents. The present study adopted both genetic and pharmacological approaches and tested the hypothesis that FAAH-deficient…
A model-based meta-analysis of sofosbuvir-based treatments in chronic hepatitis C patients.
2016
The objective of this study was to compare the efficacy of sofosbuvir-based treatments in patients with chronic hepatitis C virus (HCV) infection using a model-based meta-analysis (MBMA). A bibliographic search was performed to identify clinical trials involving sofosbuvir as a unique direct-acting antiviral (DAA) agent or together with daclatasvir, ledipasvir or simeprevir for the treatment of diagnosed HCV infection. The time course of the virological response (VR) was modelled to estimate the effect of treatment and the influence of population characteristics on the longitudinal efficacy profile. The model was validated and simulations of 10 different treatment schedules were performed. …
High Cure Rate With 24 Weeks of Daclatasvir-Based Quadruple Therapy in Treatment-Experienced, Null-Responder Patients With HIV/Hepatitis C Virus Geno…
2015
BACKGROUND Few direct anti-hepatitis C virus (HCV) agents have been studied in difficult-to-treat null responder and cirrhotic human immunodeficiency virus (HIV)-coinfected patients. Daclatasvir and asunaprevir combined with pegylated interferon/ribavirin (peg-IFN/RBV) have shown promising results in HCV-monoinfected patients. METHODS An open-label, single-arm, phase 2 study was conducted in HIV/HCV genotype 1/4-coinfected patients who were null responders to prior peg-IFN/RBV standard therapy and on a raltegravir-based regimen with HIV RNA <400 copies/mL. They received a 4-week lead-in phase with peg-IFN/RBV, followed by 24 weeks of asunaprevir (100 mg twice daily), daclatasvir (60 mg once…
Effect of cholinergic stimulation in early Alzheimer's disease - functional imaging during a recognition memory task.
2011
Treatment of Alzheimer's disease (AD) with acetylcholinesterase inhibitors (AChEI) enhances cholinergic activity and alleviates clinical symptoms. In the present functional magnetic resonance imaging (fMRI) study, we investigated the effect of the AChEI rivastigmine on cognitive function and brain activation patterns during a face recognition memory task. Twenty patients with newly-diagnosed mild AD were administered a single oral dose of placebo, a single dose of rivastigmine (acute), and twice-daily treatment with rivastigmine for 4 weeks (chronic). After each treatment, the patients underwent a facial recognition task during fMRI. The prefrontal areas known to be involved in face recogni…
Photo-induced chemiluminometric determination of Karbutilate in a continuous-flow Multicommutation assembly
2006
The present paper deals with the chemiluminescent determination of the herbicide Karbutilate on the basis of its previous photodegradation by using a low-pressure Hg lamp as UV source in a continuous-flow multicommutation assembly (a solenoid valves set). The pesticide solution was segmented by a solenoid valve and sequentially alternated with segments of the 0.001 mol l(-1) of NaOH solution, the suitable media for the formation of photo-fragments; then it passes through the photo-reactor and was lead to the flow-cell after being divided in small segments which were sequentially alternated with the oxidizing system; 2 x 10(-5) mol l(-1) of potassium permanganate in 0.2% pyrophosphoric acid.…
NMDA receptor antagonist felbamate reduces behavioral deficits and blood-brain barrier permeability changes after experimental subarachnoid hemorrhag…
2007
Increased levels of glutamate and aspartate have been detected after subarachnoid hemorrhage (SAH) that correlate with neurological status. The NMDA receptor antagonist felbamate (FBM; 2-phenyl-1,3-propanediol dicarbamate) is an anti-epileptic drug that elicits neuroprotective effects in different experimental models of hypoxia-ischemia. The aim of this dose-response study was to evaluate the effect of FBM after experimental SAH in rats on (1) behavioral deficits (employing a battery of assessment tasks days 1-5 post-injury) and (2) blood-brain barrier (BBB) permeability changes (quantifying microvascular alterations according to the extravasation of protein-bound Evans Blue by a spectropho…
HCV cirrhosis at the edge of decompensation: Will paritaprevir with ritonavir, ombitasvir, dasabuvir, and ribavirin solve the need for treatment?
2014
BACKGROUND: The interferon-free combination of the protease inhibitor ABT-450 with ritonavir (ABT-450/r) and the NS5A inhibitor ombitasvir (also known as ABT-267) plus the nonnucleoside polymerase inhibitor dasabuvir (also known as ABT-333) and ribavirin has shown efficacy against the hepatitis C virus (HCV) in patients with HCV genotype 1 infection. In this phase 3 trial, we evaluated this regimen in previously untreated patients with HCV genotype 1 infection and no cirrhosis. METHODS: In this multicenter, randomized, double-blind, placebocontrolled trial, we assigned previously untreated patients with HCV genotype 1 infection, in a 3:1 ratio, to an active regimen consisting of a single-ta…