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Acute oral administration of ethanol (3.2g/kg) to rats increased (DOPAC) levels in the caudate nucleus, but had no effect on DOPAC levels in the substantia nigra and frontal cortex and failed to modify dopamine content in any of the above areas. On the other hand, the administration of the same dose of ethanol to rats which had been chronically treated with ethanol (3.2g/kg daily for 60 days), produced a decrease of DA content and a parallel increase of DOPAC levels in all areas studied. In chronically treated rats, 24 hrs after last ethanol administration dopamine levels in the frontal cortex were 60% higher than in controls. The results suggest that ethanol administration causes dopamine release in different brain areas.

The agonist activity of the title compounds on GABA(c) receptor as well as GABA uptake inhibition activity is reported. B3LYP/6-311++G(d,p) calculations have been performed to obtain the quantum chemical descriptors such as global hardness, electrophilicity, the electronic chemical potential of the title compounds. Polarized continuum model has been used to explore the solvent effect on activity of the title compounds in four solvent media, viz., chloroform, ethanol, DMSO, and water. The results obtained from the quantum chemical calculations show that the calculated energy gap and the global hardness, as well as molecular electrostatic potential values, are in good agreement with the experimental data. The financial support of the scientific research projects of Cumhuriyet University (F-222), Sivas, Turkey is acknowledged. All calculations have been conducted at TUBITAK (the scientific and technological Research Council), ULAKBIM (Turkish academic Network and information center), High Performance and Grid Computing Center (TR-Grid e-Infrastructure), Turkey. Cumhuriyet University, Sivas, Turkey [F-222] WOS: 000415784500004

Hemispheric specialization for linguistic functions was assessed by a dichotic listening test in 16 monolingual right-handed non-alcoholic men after the administration of a moderate dose of ethyl alcohol (0.6 g/kg b.w.; alcoholemia > 80 mg/dl). No statistical evidence supporting the hypothesis that moderate doses of alcohol affect perceptive aspects of hemispheric specialization was found.

Chronic ethanol exposure alters calcium movements and the number of dihydropyridine (DHP) binding sites in the animal brain and in cultured neural cell lines. The present study investigates the effect of ethanol treatment on dihydropyridine- and omega-conotoxin (CgTx)- labelled calcium channels in undifferentiated and differentiated NG 108-15 cells. Following differentiation, the binding of [3H] -PN 200-110 increased by 48% while [125I]-CgTx binding increased by six fold. In accordance with data in the literature, undifferentiated cells exposed to ethanol (3 days) showed a large increase (70%) in DHP binding sites. In contrast, CgTx binding sites were unmodified by the treatment. Using differentiated cells, ethanol exposure induced a significant decrease (53%) in CgTx binding sites without altering those labelled by PN 200-110 (isradipine). These findings indicate that the effect of ethanol exposure on calcium channels may be dependent on the type of channel considered and on the status of the cells treated.

Marrubium vulgare is a European medicinal plant with numerous beneficial effects on human health. The aim of the study was to isolate the plant ethanolic extract (MVE) and to investigate its anti-melanoma and anti-glioma effects. MVE was prepared by the modified pharmacopoeial percolation method and characterized by UHPLC-LTQ OrbiTrap MS. MVE dose-dependently reduced viability of melanoma (B16) and glioma (U251) cells, but not peripheral blood mononuclear cells. It arrested cell cycle in S+G2/M phase, which was associated with the activation of MAP kinase p38 and up-regulation of antiproliferative genes p53, p21 and p27. MVE induced oxidative stress, while antioxidants abrogated its antitumor effect. Furthermore, MVE induced mitochondrial depolarization, activation of caspase-9 and -3, Parp cleavage, phosphatidylserine exposure and DNA fragmentation. The mitochondrial apoptotic pathway was associated with the up-regulation of proapoptotic genes Pten, Bak1, Apaf1, and Puma and down-regulation of antiapoptotic genes survivin and Xiap. MVE also stimulated the expression of autophagy-related genes Atg5, Atg7, Atg12, Beclin-1, Gabarab and Sqstm1, as well as LC3-I conversion to the autophagosome associated LC3-II, while autophagy inhibitors exacerbated its cytotoxicity. Finally, the most abundant phenolic components of MVE, ferulic, p-hydroxybenzoic, caffeic and chlorogenic acids, did not exert a profound effect on viability of tumor cells, suggesting that other components individually or in concert are the mediators of the extracts' cytotoxicity. By demonstrating the ability of MVE to inhibit proliferation, induce apoptosis and cytoprotective autophagy, our results suggest that MVE, alone or combined with autophagy inhibitors, could be a good candidate for anti-melanoma and anti-glioma therapy.

Objectives: To evaluate the effectiveness of an energy conservation management (ECM) intervention versus an MS-nurse control intervention for treating fatigue in persons with multiple sclerosis (MS). Design: Single-blind, two-parallel-arms randomized clinical trial (RCT). Setting: Two outpatient rehabilitation departments. Subjects: Adult persons with definite MS, severe fatigued, and being ambulatory. Interventions: The individual-based ECM intervention (12 sessions in 4 months) is based on the Packer group program and was given by occupational therapists. The control intervention (3 sessions in 4 months) consisted of MS-nurse consultations. Method: Primary outcome measures were Fatigue (Checklist Individual Strength-CIS20r domain subjective experience of fatigue) and participation (Impact on Participation and Autonomy- IPA). Additional secondary outcome measures on fatigue, activity and participation were done. Measurements, evaluated by blinded assessors, were at baseline and 8, 16, 26 and 52 weeks after randomization. Linear Mixed Models analyses with a three level structure (repeated measures, patients and therapists) were performed. Results: Intention to treat analysis was based on 76 patients (ECM n=36; MS-nurse n=40). No significant intervention effects were found for fatigue (overall difference CIS20r between the groups = -0.81; 95% CI -3.71 to 2.11; p=0.58), and for four out of five IPA domains. For the IPA domain social relations, an overall unfavorable effect for the ECM group was found (difference between the groups = 0.19, 95% CI 0.03 to 0.35, p=0.02). Conclusion: Energy conservation management does not lead to significant and clinically relevant changes in fatigue and participation compared to MS nurse consultations. Although both treatments achieved a statistically significant decline of fatigue during the treatment period, and for the ECM group also at long-term followup, these effects must be considered as clinically non-relevant

The interactions of antiepileptic drugs in multiple drug treatment have been discussed. Although some combinations may lead to predictable increase or decrease of clearance of the respective drugs, most combinations will individually lead to a reduced predictability. Monitoring plasma concentrations may lead to adaptations of the choice of the drug and of the dosage regimen. Also physiological conditions control the individual clearance of antiepileptic drugs.