Self-administration in baboons and the discriminative stimulus effects in rats of bupropion,nomifensine, diclofensine and imipramine

The behavioral effects of the antidepressants nomifensine, diclofensine, bupropion, and imipramine were examined using a cocaine substitution drug self-administration procedure in baboons and a cocaine drug discrimination procedure in rats. Intravenous self-administration of the antidepressants was examined in baboons under conditions in which baseline responding was maintained by intravenous injections of cocaine HCl (0.32 mg/kg/injection). Drug was available under a fixed-ratio 80-response or 160-response schedule of intravenous injection. Each drug injection was followed by a 3-h time-out allowing a maximum of eight injections per day. The antidepressants or their vehicles were substituted for cocaine for a period of 15 days, followed by a return to the cocaine baseline. Nomifensine, diclofensine, and bupropion all maintained self-administration behavior at levels above those maintained by their respective vehicles. Some doses of nomifensine, diclofensine, and bupropion maintained levels of behavior similar to those maintained under baseline cocaine conditions. High doses of imipramine maintained levels of behavior above those maintained by its vehicle, but the amount of behavior maintained under these conditions was extremely small. In a second experiment rats were trained to discriminate 32 µmol/kg cocaine (IP 10 min presession) from no drug in a two-lever food reinforced drug discrimination procedure in which responding on one lever was reinforced following ten consecutive responses when the session was preceded by cocaine administration, while responding on the other lever was similarly reinforced in the absence of cocaine pretreatment. Cocaine, nomifensine, diclofensine, and bupropion all dose-dependently occasioned cocaine-appropriate responding. Imipramine did not occasion cocaine-appropriate responding over a range of behaviorally active doses.     

Differentiation between the stimulus effects of (+)-lysergic acid diethylamide and lisuride using a three-choice,drug discrimination procedure

The discriminative stimulus properties of (+)-lysergic acid diethylamide (LSD) and lisuride hydrogen maleate (LHM), were compared in a three-choice, water reinforced (FR 20) situation in which rats were required to press one lever following LSD (0.08 mg/kg), a second lever following LHM (0.04 mg/kg), and a third lever following saline. Reliable drug-appropriate responding was established in 72 sessions. Dose-response tests with LSD and LHM indicated that, as dose increased, the per cent of responding on the lever associated with the particular training drug also increased; little or no cross-transfer occurred between LSD and LHM. In generalization tests, the serotonin (5-HT) agonist quipazine substituted for LSD but not LHM while the dopamine (DA) agonist apomorphine mimicked LHM but not LSD; an unrelated compound, pentylenetetrazol (PTZ), produced responding on the saline-appropriate lever. In combination tests, 5-HT antagonists (e.g., BC-105 and low doses of pirenperone) blocked responding on the LSD lever while DA antagonists (e.g., haloperidol and much higher doses of pirenperone) blocked LHM-appropriate responding. These data suggest that the three-lever (D-D-N) procedure is similar to, but can be more sensitive than the two-lever (D-N) procedure (because it can differentiate between LSD and LHM); they therefore at least partially support the hypothesis that three-choice discriminations can be conceptualized as two separate, two-choice (D-N) discriminations (Jarbe and Swedberg 1982). The results also confirm suggestion that the stimulus effects of LSD and LHM are mediated by different mechanisms; the primary action of LSD is serotonergic (5-HT₂), while that of LHM is dopaminergic (White 1986).Some of these data were presented at the meeting of the Society of Neuroscience, Toronto, 1988 (Satellite Session of the Society for the Stimulus Properties of Drugs). They were also submitted (in somewhat different form) to the Graduate School of the University of South Carolina in partial fulfillment of the requirements for an MA degree (in Experimental Psychology)     

白蛋白微球作为肝靶向给药载体的研究

用均匀设计方法和计算机技术筛选了乳化化学交联法制备白蛋白微球的六个因素,十二个水平。优化出最佳制备工艺,制备了平均粒径0.41～0.47μm的白蛋白微球。将此工艺制备的¹²⁵I-白蛋白微球做动物体内研究,结果表明微球iv后主要浓集在肝脏,可达注入总剂量的68%,此微球在靶组织肝脏的变化规律可用二室模型契合。     

药物敏感试验指导肺癌合并恶性胸腔积液的顺铂联合其他药物胸腔内化疗

目的用药物敏感试验预测肺癌合并恶性胸腔积液癌细胞对顺铂联合其他药物的敏感度，观察其在指导此类患者的顺铂联合其他化疗药物胸腔内化疗的价值。方法将44例胸腔积液癌细胞阳性肺癌患者随机分为两组：药物敏感试验组（20例，有2例因体外药物敏感试验失败而被排除）和对照组（22例）。药物敏感试验组患者用三磷酸腺苷-肿瘤细胞药物敏感试验（ATP-TCA）法分别检测胸腔积液癌细胞对顺铂加香菇多糖、顺铂加甘露聚糖肽、顺铂加A群链球菌制剂、顺铂加干扰素、顺铂加金黄色葡萄球菌滤液制剂、顺铂加卡介苗多糖核酸、顺铂加红色诺卡菌细胞壁骨架、顺铂加白细胞介素-2的敏感度，并选择抑瘤率最高的联合化疗药物对患者进行胸腔内化疗，观察治疗后胸腔积液完全缓解率及胸腔积液癌细胞转阴率，并与对照组比较。结果药物敏感试验组患者对各联合化疗药物敏感的例数为：顺铂加香菇多糖14例、顺铂加甘露聚糖肽18例、顺铂加A群链球菌制剂17例、顺铂加干扰素10例、顺铂加金黄色葡萄球菌滤液制剂16例、顺铂加卡介苗多糖核酸15例、顺铂加红色诺卡菌细胞壁骨架17例、顺铂加白细胞介素-216例。药物敏感试验组完全缓解率为65．0％，对照组为27．3％（P〈0．05）。药物敏感试验组胸腔积液癌细胞转阴率为80．0％，对照组为45．5％（P〈0．05）。结论用药物敏感试验指导肺癌合并恶性胸腔积液的胸腔内个体化化疗可提高完全缓解率和胸腔积液癌细胞转阴率，该方法具有临床实用价值。     

Investigation of Direct Causes of Drug Relapse and Abstainers’ Demands in a Compulsive Detoxification Center in Wuhan City of China

Objective To identify the direct causes of drug relapse and abstainers’ demand, and to develop programs for the prevention of drug relapse. Methods Abstainers in a Compulsive Detoxification Center in Wuhan City, capital of Hubei Province were randomly selected. An investigation on the direct causes of drug relapse and abstainers’ demands was conducted with multiple-choice questionnaires and face to face interviews. Data were analyzed with SPSS 12.0. Results The direct causes leading to drug relapse included: temptation to use drug again by themselves or by their drug mates, seeking pleasure and ecstasy from drug use, relatively well off living, mental stress, irritation, demoralization, family conflicts, unemployment, feeling distrusted by the family, lack of care and love from the family, and discrimination by others. abstainers’ demands after detoxification and returning to the society included: care and support from the family, employment assistance, changing living environment, understanding by others, support from the society, and keeping far away from drugs. Conclusions Environmental factors are the direct causes of drug relapse, and negative irritation is its predisposing causes. Leaving former residence, more care and help given by both the family and the society and raising their overall quality of life are the demands of abstainers.     

药物洗脱支架直接置入治疗A型和B_1型病变的临床观察

目的　评价直接置入药物洗脱支架 (CYPHERTM,codis)在A或B1 型病变的冠心病患者治疗中的安全性、可行性。方法　 6 2例接受CYPHERTM 支架直接置入的患者 (直接支架组 )和一般情况匹配的 5 1例球囊扩张后行冠脉支架术的患者 (常规支架组 ) ,比较两组的一般情况 ,冠脉造影及介入治疗即刻和临床随访结果。结果　直接支架组介入操作时间明显短于常规支架组 [(17.2± 8.6 )比 (2 6 .3± 7.1)min ,P <0 .0 1],直接支架组平均扩张压明显高于常规支架组 [(14± 3)比 (12± 1.9)atm ,P<0 .0 1],两组无一例发生介入治疗相关的严重心脏事件。随访期间两组严重心脏不良事件发生率无显著差异。结论　A或B1 型病变的冠心病患者CYPHERTM 支架直接置入术可缩短介入操作时间 ,即刻效果、并发症及中期临床随访与常规支架组差异无显著性意义     

应用抗凝剂的心脏瓣膜置换患者接受胆道手术的术前处理

目的总结瓣膜置换患者行胆道手术的术前用药方法。方法对38例瓣膜置换后在服用华法令过程中因胆道疾病需行择期手术治疗的患者随机分为2组,肝功能正常组(A组)23例、肝功能不正常组(B组)15例均于术前3d停服华法令,B组术前12h肌注VitK110mg。术前无应用华法令历史的患者115例做为对照组。结果38例患者停药2d后A组血浆凝血酶原时间与对照组差异无显著意义,B组于术前12h肌注VitK110mg后,血浆凝血酶原时间与对照组相比差异也无显著性意义。结论瓣膜置换患者在抗凝期间行胆道手术,只要准备充分,围手术期是安全的。     

肠易激综合征Manning诊断标准的评价

目的 评价Manning标准诊断肠易激综合征(IBS)的真实性。方法 采用自行设计的调查表对499例对象进行调查。结果 1．随着Manning标准中结合指标数的增多，IBS组与非溃疡性消化不良及溃疡性结肠炎组鉴别的灵敏度及其95％CI明显下降，特异度及其95％CI明显上升，同时阳性预测值、阳性似然比及阴性似然比也明显上升。2．符合Manning标准中二项以上结合指标，IBS组就具有较好与健康对照组鉴别的灵敏度及其95％CI、特异度及其95％CI。结论 Manning标准中需要3项以上结合指标可较好地使IBS与非溃疡性消化不良或溃疡性结肠炎鉴别；2项以上结合指标可较好地使IBS与健康人鉴别。     

胶原材料在药物缓释和组织工程中的研究进展

目的介绍胶原材料在药物缓释和组织工程中的研究新进展. 方法广泛查阅近年相关文献并进行回顾与综合分析. 结果胶原材料在药物缓释与组织工程中的应用研究已取得明显进展,胶原材料已成为组织工程研究的热点之一.一些胶原基质新型药物缓释系统和新型组织工程材料已进入临床论证阶段,将促进胶原材料在组织修复中的临床应用. 结论胶原材料在药物缓释、尤其是组织工程领域具有广阔的应用前景.除将胶原适当交联处理或与其它天然或合成高分子复合外,今后的研究中还应注重利用化学修饰改善胶原性能,通过将性质不同的支链接枝到胶原大分子上,赋予胶原新的特性,从而研制出新一代组织工程材料.     

耐药性癫(癎)患者颞叶中细胞周期依赖性蛋白激酶5的表达

目的 研究细胞周期依赖性蛋白激酶5(cyclin dependent kinases 5,CDK5)在耐药性癫(癎)患者颞叶中的表达,探索其在耐药性癫(癎)发病机制中的作用.方法 收集耐药性癫(癎)患者术后脑组织,用荧光定量PCR、免疫组化和Western blot 3种检测方法从基因和蛋白水平分别测定CDK5在耐药性癫(癎)患者颞叶中的表达,并与对照组进行比较.结果 荧光定量PCR发现CDK5 mRAN比对照组明显增加,免疫组化检测显示这种基因的蛋白表达产物主要分布在神经元轴突和胶质细胞中,Western blot检测在相对分子质量35 000处有一蛋白条带,并且可见实验组(颞叶和海马中分别为1.4293±0.1839和2.0733±0.4738)高于对照组(颞叶和海马中分别为0.9680±0.4147和1.403±0.6163,P＜0.05).结论 CDK5在耐药性癫(癎)患者颞叶中表达增强,提示他们可能参与了耐药性癫(癎)的形成.