OBJECTIVE Alcoholism is one of the most damaging psychiatric disorders and causes serious social and health problems in the world. However,there are no ideal treatments for this disease in clinic.Phosphodiesterases(PD...OBJECTIVE Alcoholism is one of the most damaging psychiatric disorders and causes serious social and health problems in the world. However,there are no ideal treatments for this disease in clinic.Phosphodiesterases(PDEs) are a superfamily of enzymes consisting of 11 PDE families that hydrolyze cyclicAMP(cA MP) and/or cyclicGMP(cGMP). Among them,PDE4 is critical in the control of intracellular cAMP levels and has been shown to play an important role in the regulation of ethanol consumption.However,the functional role of PDE4 in mediating alcoholism remains unclear. METHODS Ethanol drinking and preference were examined using the two-bottle choice and/or drinking-in-dark(DID) test in high alcohol preferring(HAP) animals,including C57,HAP,and PDE4-subtype knockout mice,and Fawn-Hooded(FH/Wjd) rats,treated with or without the PDE4 inhibitor rolipram or roflumilast. Ethanol withdrawal-induced anxiety-and depressive-like behaviors were examined using the elevated plusmaze,holeboard,forced-swim,and tail-suspension tests in C57 mice or FH rats in the presence of PDE4 inhibition. Levels of cAMP,CREB were determined in brain regions. RESULTS Treatment with rolipram or roflumilast decreased ethanol intake and preference in two-bottle choice and DID tests in C57 and HAP mice as well as FH rats. Mice deficient in PDE4 B,but not PDE4 D,displayed similar effects to general PDE4 inhibition. In addition,rolipram reversed ethanol withdrawal-induced anxietyand depressive-like behaviors 1 d and 14 d,respectively,following withdrawal from ethanol drinking in the two-bottle choice in C57 mice or FH rats. Locomotor activity was not changed in either mice or rats treated with the PDE4 inhibitors. Levels of cAMP,p CREB in the brain were increased by rolipram.CONCLUSION The results provide solid evidence for the important role of PDE4 in ethanol consumptionand ethanol withdrawal-induced symptoms. Inhibitors of PDE4,in particular the PDE4 B isoform,can be a novel class of treatment for alcoholism.展开更多
文摘OBJECTIVE Alcoholism is one of the most damaging psychiatric disorders and causes serious social and health problems in the world. However,there are no ideal treatments for this disease in clinic.Phosphodiesterases(PDEs) are a superfamily of enzymes consisting of 11 PDE families that hydrolyze cyclicAMP(cA MP) and/or cyclicGMP(cGMP). Among them,PDE4 is critical in the control of intracellular cAMP levels and has been shown to play an important role in the regulation of ethanol consumption.However,the functional role of PDE4 in mediating alcoholism remains unclear. METHODS Ethanol drinking and preference were examined using the two-bottle choice and/or drinking-in-dark(DID) test in high alcohol preferring(HAP) animals,including C57,HAP,and PDE4-subtype knockout mice,and Fawn-Hooded(FH/Wjd) rats,treated with or without the PDE4 inhibitor rolipram or roflumilast. Ethanol withdrawal-induced anxiety-and depressive-like behaviors were examined using the elevated plusmaze,holeboard,forced-swim,and tail-suspension tests in C57 mice or FH rats in the presence of PDE4 inhibition. Levels of cAMP,CREB were determined in brain regions. RESULTS Treatment with rolipram or roflumilast decreased ethanol intake and preference in two-bottle choice and DID tests in C57 and HAP mice as well as FH rats. Mice deficient in PDE4 B,but not PDE4 D,displayed similar effects to general PDE4 inhibition. In addition,rolipram reversed ethanol withdrawal-induced anxietyand depressive-like behaviors 1 d and 14 d,respectively,following withdrawal from ethanol drinking in the two-bottle choice in C57 mice or FH rats. Locomotor activity was not changed in either mice or rats treated with the PDE4 inhibitors. Levels of cAMP,p CREB in the brain were increased by rolipram.CONCLUSION The results provide solid evidence for the important role of PDE4 in ethanol consumptionand ethanol withdrawal-induced symptoms. Inhibitors of PDE4,in particular the PDE4 B isoform,can be a novel class of treatment for alcoholism.
文摘目的:系统评价微生态制剂阴道胶囊对细菌性阴道炎(bacterial vaginosis,BV)的治疗效果及安全性。方法:以"微生态制剂"、"乳酸杆菌"、"细菌性阴道炎"、"阴道炎"、"随机对照试验"等为关键词,分别检索Pub Med(1966—2016年)、荷兰医学文摘(1966—2016年)、中国期刊全文数据库(1979—2016年)和中国生物医学文献数据库(1978—2016年)。收集微生态制剂治疗BV的病例对照研究文献。根据纳入标准对文献进行筛选和评估,采用Rev Man 5.3软件对数据进行Meta分析。结果:共纳入了11项随机对照试验进行分析。结果显示,抗菌药联合微生态制剂阴道胶囊治疗BV后,微生态制剂组患者治疗率与对照组没有显著差异(RR=1.15,95%CI:0.93~1.40,P=0.19)。报告的总体不良反应事件也没有显著性差异(RR=0.98,95%CI:0.82~1.17,P=0.83)。结论:与安慰剂对照研究的结果证明,益生菌组不提高治疗BV的临床疗效。结果没有提供足够的证据支持或反对建议使用益生菌治疗BV。还需要设计良好的随机对照试验进一步来验证联合益生菌治疗的效果。
