21 research outputs found

    Alterations in ethanol-induced behaviors and consumption in knock-in mice expressing ethanol-resistant NMDA receptors

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    Ethanol's action on the brain likely reflects altered function of key ion channels such as glutamatergic N-methyl-D-aspartate receptors (NMDARs). In this study, we determined how expression of a mutant GluN1 subunit (F639A) that reduces ethanol inhibition of NMDARs affects ethanol-induced behaviors in mice. Mice homozygous for the F639A allele died prematurely while heterozygous knock-in mice grew and bred normally. Ethanol (44 mM; ∌0.2 g/dl) significantly inhibited NMDA-mediated EPSCs in wild-type mice but had little effect on responses in knock-in mice. Knock-in mice had normal expression of GluN1 and GluN2B protein across different brain regions and a small reduction in levels of GluN2A in medial prefrontal cortex. Ethanol (0.75-2.0 g/kg; IP) increased locomotor activity in wild-type mice but had no effect on knock-in mice while MK-801 enhanced activity to the same extent in both groups. Ethanol (2.0 g/kg) reduced rotarod performance equally in both groups but knock-in mice recovered faster following a higher dose (2.5 g/kg). In the elevated zero maze, knock-in mice had a blunted anxiolytic response to ethanol (1.25 g/kg) as compared to wild-type animals. No differences were noted between wild-type and knock-in mice for ethanol-induced loss of righting reflex, sleep time, hypothermia or ethanol metabolism. Knock-in mice consumed less ethanol than wild-type mice during daily limited-access sessions but drank more in an intermittent 24 h access paradigm with no change in taste reactivity or conditioned taste aversion. Overall, these data support the hypothesis that NMDA receptors are important in regulating a specific constellation of effects following exposure to ethanol. © 2013 den Hartog et al

    Brazilian Consensus on Photoprotection

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    Coexistence of Takayasu’s Arteritis in Patients with Inflammatory Bowel Diseases

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    Background. Takayasu’s arteritis (TA) and inflammatory bowel disease (IBD) are chronic inflammatory granulomatous disorders that have rarely been concomitantly reported in case reports and small case series. Objective. We report a series of seven cases of TA and IBD association in two referral centers with a comprehensive review of literature. Methods. We analyzed retrospectively the electronic medical charts of TA-IBD patients at the University Hospital of São Paulo, Brazil, and at the Sheba Medical Center at Tel Aviv University, Israel. Results. Overall, five patients had Crohn’s disease (DC) and two had ulcerative colitis (UC), and they were mostly female and non-Asian. All patients developed IBD first and, subsequently, TA. Two underwent colectomy and one ileocecectomy due to IBD activity, while three required cardiovascular surgery due to TA activity. Most patients are currently in clinical remission of both diseases with conventional drug treatment. Conclusion. Although the coexistence of TA and IBD is uncommon, both seem to be strongly associated through pathophysiological pathways