Ethanol-Induced Enhancement of Cocaine Bioactivation and Irreversible Protein Binding: Evidence Against a Role of Cytochrome P-450IIE1

Chronic ethanol consumption potentiates cocaine-induced liver injury in rodents. Since cocaine has to be bioactivated by a cytochrome P-450-dependent N-oxidative pathway to exert its hepatotoxic effects, we studied the role of the ethanol-inducible P-450IIE1 for cocaine metabolism. Male Sprague-Dawley rats were pretreated with either a liquid diet containing ethanol (30% of calories) for 4 weeks or injected with pyrazole (200 mg/kg/day, ip, for 3 days). Both agents induced microsomal p-nitrophenol hydroxylation which is a probe for the catalytic activity of P-450IIE1. However, only ethanol, but not pyrazole, increased both microsomal cocaine N-demethylase activity (by 47%) and the extent of irreversible binding of [3H]-cocaine to microsomal proteins (by 100%), which was taken as a quantitative endpoint for the formation of a reactive metabolite. Cocaine N-demethylation and irreversible protein binding of cocaine were not inhibited by P-450IIE1 isozyme-selective substrates, nor was the rate of cocaine metabolism and binding decreased by functionally active polyclonal anti-rat P-450IIE1 antibodies. Furthermore, pyrazole pretreatment sensitized cultured hepatocytes to the glutathione-dependent cytotoxic effects of nontoxic concentrations of cocaine. These results indicate that (a) cocaine is not a major substrate for the ethanol-inducible P-450IIE1, (b) the enhancing effects of ethanol on cocaine bioactivation may be due to induction of other P-450 isoforms, and (c) induction of P-450IIE1 may potentiate cocaine-induced hepatocellular toxicity in vitro independently of cocaine metabolism, e.g., by P-450IIE1-dependent oxidative stress.     

Recombinant cysteine proteinase from Leishmania (Leishmania) chagasi implicated in human and dog T-cell responses

High in vitro lymphoproliferative responses were induced in humans and dogs by a recombinant Leishmania (Leishmania) chagasi cysteine proteinase, with secretion of IFN-gamma in asymptomatic subjects or of IFN-gamma, interleukin 4 (IL-4), and IL-10 in oligosymptomatic subjects. In contrast, responses of symptomatic patients and dogs were lower, with production of IL-4 and IL-10.     

我国西部药学教育现状及发展建议

发展药学教育对西部开发具有重要意义。希望各级政府主管部门制定特殊政策，加大投入力度，统筹规划学校设置与专业布局，加速发展药学教育事业。     

药事管理学科科研问题及对策浅析

分析当前我国药事管理学科科研中存在的问题和原因。提出发展科研的思路与方法。     

建设我国药学职业道德规范的思考

探讨建设我国药学职业道德规范的思路；阐释和分析建设药学职业道德规范应明确的基本概念及药学职业道德规范的基本内容；建设我国药学职业道德规范，需明确药学职业的责，权，利所在，明确药学职业法律规范与道德规范的关系，明确药学职业道德规范的制定和监督部门。加强药学职业道德教育和继续教育。     

注射用伏立康唑无菌检查法的建立

目的：确定新药伏立康唑注射用无菌粉末的无菌检查法。方法：无菌检查法的验证试验——抑细菌和抑真菌试验及冲洗量试验。通过菌悬液的制备、培养基的检查、冲洗量的选择、阳性对照菌的选择及加入顺序等全过程，说明无菌检查法的建立，必须有验证试验的保证。结果：该药的无菌检查选用薄膜过滤法，以黑曲霉为阳性对照菌，冲洗总量1500ml。结论：通过验证试验保证的无菌检查条件检查该药，方法可行，结果可靠。应在药品检验工作中，逐步完善微生物检验方法学的内容，从而提高我国药品微生物检验工作的总体水平。     

药品检验所微生物实验室质量管理规范问题的浅见

国家颁布的药品检验所实验室质量管理规范中,对微生物实验室质量管理规范有的是原则性的规定,没有实施细则,有的制度则要求各所补充制定,执行起来有可能不规范。药品检验所是国家对药品质量实施监督检验的法定机构,每一项检验都承担着严肃的法律责任。实验室质量管理规范是实现实验室的标准化、规范化和管理科学化,确保药品检验数据及检验结论的科学、公正、优质的重要基础和技术保证。微生物实验室亦不例外。但在药检所计量认证及实验室认可中对微生物实验室检查指导较少。正如美国FDA 药品质量控制微生物实验室