Facilitation of ethanol consumption by intracerebroventricular infusions of corticosterone

Male Wistar rats bearing intracerebroventricular (ICV) cannulae and with simultaneous access to 6% ethanol and water were subjected to adrenalectomy (ADX) or sham surgery. ADX decreased ethanol intake. Starting a few days later, the animals received ICV infusions with 100 μg corticosterone acetate (CORT) with 2-to 3-day intervals for 2 weeks. ICV CORT, but not SC CORT at the same dose, restored ethanol consumption in ADX rats to preoperative levels, whereas vehicle infusions (propylene, glycol) did not. Adrenally intact animals, which normally consumed moderate amounts of ethanol (≈0.5 g/kg per day), also showed a robust effect of ICV infusions of CORT, whereas this facilitatory effect was not observed in high consumers (≈3.0 g/kg per day). The suppressive effect of ADX on ethanol intake was not reproduced by concurrent and repeated ICV infusions of intracellular mineralocorticoid (RU 28318) and glucocorticoid (mifepristone) receptor blockers. It is concluded that CORT stimulates alcohol consumption by acting in the brain, probably by way of neuronal membrane mechanisms.     

呋苄青霉素药代动力学及组织分布的研究

呋苄青霉素是由我国开发成功的一个酰脲类青霉素。本项研究采用微生物法,以狗和正常人为受试对象,以氧哌嗪青霉素和羧苄青霉素为对照进行药代动力学研究,结果表明,3个药的药—时曲线符合二室开放式模型,呋苄青霉素较其它对照药具较高的即刻血浓度和较低的肾清除率。用微生物法和放射自显影法测定的呋苄青霉素在小鼠体内组织分布汪明,呋苄青霉素广泛分布于体内各组织,尤其在肺、肝、肠中的浓度明显高于羧苄青霉素。     

How adverse drug reactions can play a role in innovative drug research

We describe how adverse drug reactions (ADRs) can play an important role in pharmaceutical research and drug development. Not only do ADRs represent the risks and drawbacks associated with drugs but they can also be related to other knowledge available in pharmaceutical and medical research. We offer a model that can be used to systematically map the pathways through which ADRs can lead to innovative research. These pathways include chemical, therapeutic or pathophysiological steps that can be taken to arrive at new knowledge based on ADRs. We used the development of angiotensin-converting enzyme inhibitors, especially captopril, as a case study. The similarity between the ADR profiles of captopril and penicillamine was a starting point for further innovation. Historical analysis shows that in several instances research in the field of angiotensin-converting enzyme inhibitors has been triggered by ADRs. The model presented here might be applicable to other areas of innovative drug research.     

口服Sumatriptan治疗偏头痛的临床评价

本文报告口服Sumatriptan 100mg对偏头痛急性发作119例次的治疗结果。治疗后4h内显效91例次(76.5％),好转16例次(13.4％),无效12例次(10.1％),总有效率为89.9％。对偏头痛伴随症状恶心、呕吐和畏光、畏声的缓解率分别为94.2％、96％和94.3％。     

腹腔镜手术病人咪达唑仑-芬太尼-异丙酚麻醉诱导的优化配伍方案

目的 采用权重配方法探讨腹腔镜手术病人咪达唑仑、芬太尼、异丙酚复合麻醉诱导的优化配伍方案。方法选择ASAⅠ或Ⅱ级择期腹腔镜手术病人60例，男34例，女26例，年龄31～55岁。诱导药物的低效量和足量分别确定为咪达唑仑0．02、0．06mg／kg，芬太尼2、6μg／kg，异丙酚0．5、1．5mg／kg。根据权重配方法，将病人随机分配至3种药物不同剂量组合的6个配伍组（n=10）。连续监测脑电双频谱指数（BIS）、心率（HR）、平均动脉压（MAP）、脉搏血氧饱和度（SpO2）。各组依次静脉注射相应剂量咪达唑仑、芬太尼、异丙酚和罗库溴铵0．6mg／kg行麻醉诱导和气管插管。记录诱导前即刻、异丙酚注入后1、2min、插管即刻、插管后1、3、5、7min的BIS、MAP及HR。按权重配方法的剂量优化原则评判复合药效，分析各组份药的重要程度及相互作用的性质。结果以BIS为评价指标，当咪达唑仑0．06mg／kg、芬太尼5μg／ks、异丙酚1．0mg／kg配伍时，异丙酚为主药，异丙酚与咪达唑仑和芬太。尼具有相加性作用；以MAP为评价指标，当咪达唑仑0．06mg／kg、芬太尼5μg，kg、异丙酚1．5mg／kg配伍时，异丙酚为主药，异丙酚与咪达唑仑具有协同性作用，异丙酚与芬太尼具有相加性作用；以HR为评价指标，当咪达唑仑0．06mg／kg、芬太尼5μg／kg、异丙酚1．0mg／kg配伍时，芬太尼为主药，异丙酚与咪达唑仑和芬太尼具有协同性作用。结论腹腔镜手术病人咪达唑仑、芬太尼、异丙酚复合麻醉诱导在维持镇静方面为相加作用，在维持血液动力学稳定方面为协同作用；优化配伍方案为咪达唑仑0．06mg／kg、芬太尼5μg／kg、异丙酚1．5mg／kg。     

四类抗感染药物不良反应相关因素的探讨与分析

目的：使输液疗法中药物不良反应降到最低限度，使患者获得安全、有效的治疗，同时，也是对有限药物资源的维护。方法：对用四类抗感染药物出现不良反应91例患者行减慢输液速度、平卧、松解领扣、按合谷穴、心理护理、保暖、进饮食等处置。结果：91例药物不良反应，有89例顺利完成输液治疗，2例无效，更换药物。结论：有责任感，加强观察护理及时发现患者反应前驱症状，迅速采取有效措施，会取得满意效果。     

Discriminative stimulus properties of the serotonin agonist MK 212

In an attempt to clarify the role of 5-hydroxytryptamine (5-HT) in the discriminative stimulus properties of MK 212 (6-chloro-2[1-piperazinyl]pyrazine), male Sprague-Dawley rats were trained to discriminate 0.5 mg/kg of this compound from saline. While the putative 5-HT agonists fenfluramine and m-chlorophenylpiperazine (MCPP) mimicked MK 212 in a dose-related manner, d-lysergic acid diethylamide (LSD), 8-hydroxy-2(di-n-propylamino)tetralin (8-OHDPAT), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), quipazine, Ru 24969, and 1-(m-trifluoromethylphenyl)piperazine (TFMPP) failed to substitute completely. The 5-HT₁/5-HT₂ antagonists BC 105, metergoline, and methysergide completely blocked the MK 212 cue, while the selective 5-HT₂ antagonists ketanserin and pirenperone, the dopamine antagonists haloperidol and spiperone, and the beta-noradrenergic antagonist propranolol were without effect. The substitutions of fenfluramine and MCPP for MK 212 support a role for 5-HT in the MK 212 cue; however, the lack of substitution of many other 5-HT agonists is difficult to explain. The complete antagonism by 5-HT₁/5-HT₂ but not by selective 5-HT₂, antagonists suggests the possibility that 5-HT₁ receptors mediate the stimulus properties of MK 212. Further research is needed to support this hypothesis and to investigate the relative role of 5-HT and other neurotransmitters in the stimulus effects of MK 212.Portions of this research were presented at the Meeting of the Committee on Problems of Drug Dependence Satellite Session (International Study Group Interested in Drugs as Reinforcers and the Society for the Stimulus Properties of Drugs) in Baltimore, MD (1985)     

应用3H-TdR掺入法对SMMC-7721细胞株药敏试验条件的探讨与应用

目的探讨3H-TdR掺入法在进行SMMC-7721系细胞肿瘤药敏试验实验时的最佳实验条件.方法确定出3H-TdR掺入法药敏实验时的最适细胞浓度、最适实验药物浓度、3H-TdR掺入最适时间;在最适条件下采用3H-TdR掺入法测定肝癌SMMC-7721细胞株对临床常用的9种抗癌药物的敏感性.结果应用3H-TdR掺入法检测肝癌SMMC-7721细胞株药敏试验的最适实验细胞浓度为1×104个/孔,最适试验药物浓度为1×PPC,3H-TdR最适掺入时间为收集细胞前8 h;肝癌SMMC-7721细胞株对DDP、ADM、5-FU、CPT高度敏感,对MTX、VP-16、MMC、NVB低度敏感,对PYM不敏感.结论 3H-TdR掺入法可用于肿瘤药物敏感性测定并确定出它的最适实验条件.     

泌尿系感染病原菌的变迁及耐药性分析

目的了解近年来泌尿系感染病原菌的变迁及耐药现状. 方法应用回顾性调查分析方法,对我院1997至2000年间泌尿系感染检测的1 026株病原菌的分布及耐药性进行统计分析. 结果在泌尿系感染的病原菌中,G+球菌上升,G-杆菌下降,真菌上升,其中粪肠球菌上升和变形菌属下降差异有显著性(P<0.05),药敏实验结果对以往常用的抗菌药物青霉素类、复方新诺明、红霉素、诺氟沙星及一代头孢显示较高的耐药性,2000年耐药率>81.6%,对三代头孢、环丙沙星、庆大霉素呈中度耐药,耐药率在42.9%～78.3%,对阿米卡星及头孢哌酮/舒巴坦呈轻度耐药,耐药率<36.7%. 结论随着抗生素的更新换代、人口老龄化及医院感染等因素的变化,泌尿系感染病原菌的分布及耐药性均发生了变迁.     

Cough and converting enzyme inhibitors

Persisting cough developed in three children treated with converting enzyme inhibitors. The symptoms disappeared within 3–7 days after withdrawing medication. These observations in children complement previous reports in adults and indicate that cough may be induced by treatment with these agents.