Search results for "Naphthalenes"
showing 10 items of 90 documents
Protective activation of the endocannabinoid system during ischemia in dopamine neurons
2006
Endocannabinoids act as neuroprotective molecules promptly released in response to pathological stimuli. Hence, they may represent one component of protection and/or repair mechanisms mobilized by dopamine (DA) neurons under ischemia. Here, we show that the endocannabinoid 2-arachidonoyl-glycerol (2-AG) plays a key role in protecting DA neurons from ischemia-induced altered spontaneous activity both in vitro and in vivo. Accordingly, neuroprotection can be elicited through moderate cannabinoid receptor type-1 (CB1) activation. Conversely, blockade of endocannabinoid actions through CB1 receptor antagonism worsens the outcome of transient ischemia on DA neuronal activity. These findings indi…
Measurement of substrate-induced oxygen uptake during microsomal drug oxidation using a gold micro-electrode.
1975
1. A resin-coated gold micro-electrode has been used for polarographic determination of oxygen concentration in liver microsomal suspensions from phenobarbital-pretreated rats. 2. The rate of oxygen uptake on addition of an NADPH-regenerating system and the rate after addition of various substrates of the mixed function oxidase system were measured. The rate of oxygen uptake was faster in the presence of substrate than in the presence of NADPH alone. 3. Kinetic constants (Km and V max) for biphenyl, hexobarbital, ethylmorphine, naphthalene and SKF 525-A measured by this technique compare favourably with those obtained either by measurements of NADPH oxidation, or chemical measurements of su…
Prenatal exposure to the CB1 receptor agonist WIN 55,212-2 causes learning disruption associated with impaired cortical NMDA receptor function and em…
2005
The aim of this study was to investigate whether prenatal exposure to the cannabinoid CB1 receptor agonist WIN 55,212-2 (WIN) at a daily dose devoid of overt signs of toxicity and/or gross malformations (0.5 mg/kg, gestation days 5-20), influences cortical glutamatergic neurotransmission, learning and emotional reactivity in rat offspring. Basal and K+-evoked extracellular glutamate levels were significantly lower in cortical cell cultures obtained from pups exposed to WIN during gestation with respect to those measured in cultures obtained from neonates born from vehicle-treated dams. The addition of NMDA to cortical cell cultures from neonates born from vehicle-treated dams concentration-…
Inhibition of myosin light chain kinase reduces brain edema formation after traumatic brain injury.
2010
The role of the endothelial contractile apparatus in the process of brain edema formation after brain trauma is not characterized. Phosphorylation of myosin light chains by myosin light chain kinases (MLCK) activates endothelial contractile elements and results in a rearrangement of the cytoskeleton. This may enhance post-traumatic blood-brain barrier dysfunction. In order to investigate the role of the MLCK on brain edema formation and blood-brain barrier permeability after brain injury, mice were anesthetized and subjected to a controlled cortical impact (CCI). MLCK expression is significantly up-regulated after CCI with a maximum 12 h post-injury. Specific inhibition of MLCK by ML-7 resu…
The use of the Emotional-Object Recognition as an assay to assess learning and memory associated to an aversive stimulus in rodents
2016
Abstract Background Emotionally salient experiences induce the formation of explicit memory traces, besides eliciting automatic or implicit emotional memory in rodents. This study aims at investigating the implementation of a novel task for studying the formation of limbic memory engrams as a result of the acquisition- and retrieval- of fear-conditioning – biased declarative memory traces, measured by animal discrimination of an “emotional-object”. Moreover, by using this new method we investigated the potential interactions between stimulation of cannabinoid transmission and integration of emotional information and cognitive functioning. New method The Emotional-Object Recognition task is …
Tamibarotene in patients with acute promyelocytic leukaemia relapsing after treatment with all-trans retinoic acid and arsenic trioxide
2015
Treatment of acute promyelocytic leukaemia (APL) with arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) is highly effective first-line therapy, although approximately 5-10% of patients relapse. Tamibarotene is a synthetic retinoid with activity in APL patients who relapse after chemotherapy and ATRA, but has not been studied in relapse after treatment with ATO and ATRA. We report on a phase II study of tamibarotene in adult patients with relapsed or refractory APL after treatment with ATRA and ATO (n = 14). Participants were treated with tamibarotene (6 mg/m(2) /d) during induction and for up to six cycles of consolidation. The overall response rate was 64% (n = 9), the rate of comp…
Effects of 7-OH-DPAT and U 99194 on the behavioral response to hot plate test, in rats
2005
Aim of present study was to investigate in male Wistar rats, whether behavioral response to hot plate test application could be influenced by systemic administration of 7-OH-DPAT, a dopaminergic (DA) D3 versus D2 receptor agonist, or U 99194, a DA D3 versus D2 receptor antagonist. Each trial lasted no more than 10 s and the whole experimental session lasted 120 min. Animal behavior was recorded by means of a digital videocamera and later, frame by frame examined using a professional videorecorder. Latency of each behavioral pattern, characterizing the response, was analysed, showing significant changes only with U 99194. A multivariate cluster analysis indicated the presence of three main b…
Serotonin, the Prefrontal Cortex, and the Antidepressant-Like Effect of Cannabinoids
2007
Preclinical and clinical studies show that cannabis modulates mood and possesses antidepressant-like properties, mediated by the agonistic activity of cannabinoids on central CB1 receptors (CB1Rs). The action of CB1R agonists on the serotonin (5-HT) system, the major transmitter system involved in mood control and implicated in the mechanism of action of antidepressants, remains however poorly understood. In this study, we demonstrated that, at low doses, the CB1R agonist WIN55,212-2 [R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl) methanone mesylate] exerts potent antidepressant-like properties in the rat forced-swim test (FST). This effect …
Presynaptic effects of anandamide and WIN55,212-2 on glutamatergic nerve endings isolated from rat hippocampus
2006
We examined the effects of the endocannabinoide-anandamide (AEA), the synthetic cannabinoid, WIN55,212-2, and the active phorbol ester, 4-beta-phorbol 12-myristate 13-acetate (4-beta-PMA), on the release of [(3)H]d-Aspartate ([(3)H]d-ASP) from rat hippocampal synaptosomes. Release was evoked with three different stimuli: (1) KCl-induced membrane depolarization, which activates voltage-dependent Ca(2+) channels and causes limited neurotransmitter exocytosis, presumably from ready-releasable vesicles docked in the active zone; (2) exposure to the Ca(2+) ionophore-A23187, which causes more extensive transmitter release, presumably from intracellular reserve vesicles; and (3) K(+) channel block…
The effects of transdermal rotigotine on non-motor symptoms of Parkinson's disease: a multicentre, observational, retrospective, post-marketing study
2017
This study evaluated the effect of ≥6 months of transdermal rotigotine on non-motor and motor symptoms of patients with advanced Parkinson's disease.The study was conducted in Spain between September 2011 and December 2012 (ClinicalTrials.gov: NCT01504529). The primary efficacy variable was the change from baseline in non-motor symptoms, as assessed by changes in Parkinson's Disease Non-Motor Symptoms Questionnaire total scores at 6 months. Secondary endpoints included the assessment of motor symptoms by Unified Parkinson's Disease Rating Scale III scores.Data from 378 patients (mean age: 70.2 years; 56.9% male) with Parkinson's disease receiving rotigotine from were collected. Mean disease…