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“L-DOPA-induced dyskinesias (LID) represent a severe complication of long-time pharmacotherapy in Parkinson’s disease that necessitates novel therapeutics. The acute and chronic effects PF-4708671 mw of K(V)7.2-7.5 channel openers (retigabine, flupirtine) on the severity of LID and parkinsonian signs were examined in comparison to the glutamate receptor antagonist amantadine

(positive control) in a rat model of LID. Acute treatment with retigabine (2.5, 5 mg/kg i.p.) and flupirtine (5, 10 mg/kg i.p.) significantly reduced the severity of abnormal involuntary movements (AIM) to a comparable extent as amantadine (20, 40 mg/kg s.c.), but flupirtine delayed the disappearance of AIM. Chronic treatment with retigabine (daily 5 mg/kg i.p. over 19 days combined with L-DOPA 10 mg i.p.) did not prevent or delay the development of LID, but reduced the severity of AIM, while antidyskinetic effects of amantadine

(40 mg/kg i.p.) were restricted to the first day of treatment. Retigabine caused sedation and ataxia which declined during the chronic treatment, but did not reduce the antiparkinsonian effects of L-DOPA in these experiments. Acute co-injections of retigabine selleck products (5 mg) together with L-DOPA (10 mg/kg) neither reduced the motor performance in the rotarod test nor exerted negative effects on the antiparkinsonian efficacy of L-DOPA in the block and stepping MycoClean Mycoplasma Removal Kit test. Nevertheless, the sedative effects of retigabine may limit its therapeutic potential for the treatment of LID. The present data

indicate that K(V)7 channels deserve attention in the research of the pathophysiology of dyskinesias.

This article is part of a Special Issue entitled ‘Post-Traumatic Stress Disorder’. (C) 2011 Elsevier Ltd. All rights reserved.”
“Asymmetric cell division (ACD) is a fundamental process used to generate cell diversity during metazoan development that occurs when a cell divides to generate daughter cells adopting distinct fates. Stem cell divisions, for example, are a type of ACD and provide a source of new cells during development and in adult animals. Some ACDs produce a daughter cell that dies. In many cases, the reason why a cell divides to generate a dying daughter remains elusive. It was shown recently that denatured proteins are segregated asymmetrically during cell division. Here, we review data that provide interesting insights into how apoptosis is regulated during ACD and speculate on potential connections between ACD-induced cell death and partitioning of denatured proteins.”
“Background Glutamic acid decarboxylase (GAD) is a major target of the autoimmune response that occurs in type 1 diabetes mellitus. In animal models of autoimmunity, treatment with a target antigen can modulate aggressive autoimmunity.