Blockade of the NMDA receptor increases developmental apoptotic elimination of granule neurons and activates caspases in the rat cerebellum

Elimination of neurons produced in excess naturally occurs during brain development through programmed cell death. Among the many survival factors affecting this process, a role for neurotransmitters acting on specific receptors has been suggested. We have performed an in vivo pharmacological blockade of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors, using the competitive NMDA receptor antagonist CGP 39551 at developmental stages corresponding to those at which a survival dependence on the stimulation of this receptor has been demonstrated for cerebellar granule neurons explanted in culture (typically from postnatal day 7 to postnatal day 11 or 13). We were able to demonstrate an increased level of DNA fragmentation in the cerebellum of the treated rats. At the P11 stage, in particular, the fragmented DNA extracted from the cerebellum of CGP 39551-treated pups showed a clear laddering of nucleosomal fragments after agarose-gel electrophoresis. Accordingly, in situ TUNEL technique showed a remarkable increase of cells positive for nucleosomal DNA fragmentation, particularly in the inner granular layer of the cerebellum of treated rats at P11 stage. Therefore, the natural rate of apoptotic elimination of cerebellar granule neurons is considerably enhanced under conditions of pharmacological blockade of the NMDA receptor, thus demonstrating, for the first time in vivo, a clear survival dependence of these neurons upon the stimulation of the NMDA receptor. Concomitantly with the increased rate of apoptotic elimination of granule neurons, the activity of two death proteases of the caspase family, in particular of caspase 3 and caspase 1 at a lower extent, was remarkably increased in the cerebellum of the treated rats. On the contrary, a marker related to the normal differentiation process of granule neurons, the enzyme ornithine decarboxylase, was strongly decreased in its activity in the cerebellum of treated rat pups.     

Cannabinoids inhibit hippocampal GABAergic transmission and network oscillations

Using a new antibody developed against the C-terminus of the cannabinoid receptor (CB1), the immunostaining in the hippocampus revealed additional axon terminals relative to the pattern reported previously with an N-terminus antibody. Due to a greater sensitivity of this antibody, a large proportion of boutons in the dendritic layers displaying symmetrical (GABAergic) synapses were also strongly immunoreactive for CB1 receptors, as were axon terminals of perisomatic inhibitory cells containing cholecystokinin. Asymmetrical (glutamatergic) synapses, however, were always negative for CB1. To investigate the effect of presynaptic CB1 receptor activation on hippocampal inhibition, we recorded inhibitory postsynaptic currents (IPSCs) from principal cells. Bath application of CB1 receptor agonists (WIN55,212-2 and CP55,940) suppressed IPSCs evoked by local electrical stimulation, which could be prevented or reversed by the CB1 receptor antagonist SR141716A. Action potential-driven IPSCs, evoked by pharmacological stimulation of a subset of interneurons, were also decreased by CB1 receptor activation. We also examined the effects of CB1 receptor agonists on Ca2+-independent miniature IPSCs (mIPSC). Both agonists were without significant effect on the frequency or amplitude of mIPSCs. Synchronous gamma oscillations induced by kainic acid in the CA3 region of hippocampal slices were reversibly reduced in amplitude by the CB1 receptor agonist CP 55,940, which is consistent with an action on IPSCs. We used CB1-/- knock-out mice to confirm the specificity of the antibody and of the agonist (WIN55,212-2) action. We conclude that activation of presynaptic CB1 receptors decreases Ca2+-dependent GABA release, and thereby reduces the power of hippocampal network oscillations.     

化瘀排石汤对体外碎石后肾结石患者β2-微球蛋白含量的影响

目的：研究化痰排石汤治疗肾结石的临床效果及是否具有减轻和修复肾脏损伤的作用。方法：将60例患者随机分为治疗组(中药内服和体外碎石)和对照组(单纯体外碎石)各30例，观察两组临床疗效和碎石前24h，碎石后24h、72h、120h的血、尿β2—微球蛋白(β2—MG)含量的变化。结果：治疗组总有效率显著高于对照组；治疗组碎石前后β2—MG的含量差异无显著性。结论：化痰排石汤治疗肾结石疗效确切，具有减轻和修复肾脏损伤的作用。     

扶正抑瘤颗粒对乳腺癌核转录因子-kB及细胞周期的影响

目的：研究扶正抑瘤颗粒(FYK)对乳腺癌肿瘤组织核转录因子-κB(NF-κB)和细胞周期的影响及其临床意义。方法：55例乳腺癌患者，随机分为治疗组和对照组，两组均用常规化疗，治疗组同时口服FYK，1个月后取肿瘤组织用流式细胞仪检测NF-κB的表达情况及肿瘤细胞周期各时相的比例。结果：治疗组与对照组比较，NF-κB的表达明显提高(P＜0．01)；G0／1期细胞比例明显升高(P＜0．01)，S期细胞比例及细胞增殖指数(P1)明显下降(P＜0．01)。结论：FYK可提高乳腺癌组织NF-κB表达水平；能升高G0／1期细胞比例，降低S期细胞比例及PI值，对乳腺癌患者的预后起积极作用。     

薄层扫描法测定三九感冒灵冲剂中对乙酰氨基酚及咖啡因的含量

目的 :用薄层扫描法同时测定三九感冒灵冲剂中对乙酰氨基酚及咖啡因的含量。方法 :以氯仿 -乙酸乙酯 -甲醇 -氨水(15∶4∶3∶0 3)为展开剂 ,采用双波长反射法锯齿扫描。结果 :对乙酰氨基酚平均回收率为99 33 % ,RSD=1 28% ,3批样品的标示量分别为99 02 %、98 48 %、99 23% ;咖啡因平均回收率为100 1 % ,RSD=1 71 % ,3批样品的标示量分别为99 74%、98 57 %、99 24%。结论 :本方法简便、快速 ,测定结果准确 ,可作为该制剂的质量控制方法     

辛芩冲剂治疗变应性鼻炎的疗效和安全性分析

目的：探讨辛芩冲剂对变压性鼻炎的疗效和安全性。方法：确诊为变应性鼻炎的患者142例随机分成两组，试验组（112例）接受辛芩冲剂口服，一次5g，一日3次；对照组（30例）接受千柏鼻炎片口服，一次3片，一日3次，二种药物均用药20天。观察的症状包括喷嚏、流涕、鼻塞和鼻痒，并进行4分法评分，计算出治疗后积分改善率。结果：经过20天的治疗，辛芩冲剂治疗组的临床控制率为27．67％（31／112），显效率为43．75％（49／112），有效率为17．86％（20／112），无效率为10．71％（12／112），总有效率为89．29％（100／112）；千柏鼻炎片治疗组的临床控制率为0％（0／30），显效率为6．67％（2／30），有效率为20．00％（6／30），无效率为73．33％（22／30），总有效率为26．67％（8／30）。经统计学处理两者差异有显著性意义（P＜0．01），辛芩冲剂治疗组明显优于千柏鼻炎片治疗组，辛芩冲剂和千柏鼻炎片治疗组的病人均未发生不良反应。结论：辛芩冲具有疗效好、无毒副作用等优点，是治疗变应性鼻炎的理想药物。     

微细药物表面包覆技术在制剂中的应用

新型药物开发制备过程中，需要对药物颗粒进行粒子设计，通过多层微胶囊化而得到复合包覆药物颗粒。药物包覆、微胶囊制备方法很多，可分为化学法、物理化学法、物理法。本文着重介绍了制备复合多层包覆药物颗粒的几种物理机械方法：复合杂化系统，高速椭圆转子混合法、喷流床包覆法。简要分析了该技术用于中药现代化加工的可能性。     

小青龙汤配方颗粒与传统饮片中芍药苷含量的比较

目的 比较小青龙汤配方颗粒与传统饮片中芍药苷的含量。方法 采用高效液相色谱法进行分析比较研究。结果 该测定方法精密度、稳定性和重复性良好，平均回收率为101．78％，RSD=0．85％。结论 两种剂型中芍药苷的含量无明显差异。     

金叶败毒方之免煎颗粒与传统饮片对小鼠抗炎及免疫功能影响的比较研究

目的探讨金叶败毒方之免煎颗粒与传统饮片在抗炎及增强免疫功能等药效方面的差别。方法分别以昆明种小鼠建立炎症和免疫功能低下动物模型,分别对金叶败毒方之免煎颗粒与传统饮片设立大、小剂量组;采用经典的小鼠耳肿实验和血管通透性实验验证金叶败毒方的抗炎功效,而以小鼠腹腔巨噬细胞吞噬实验和溶血素测定实验为反映免疫功能的指标。结果金叶败毒方之免煎颗粒与传统饮片均有抗炎和增强免疫功能的作用,且两种制剂之大剂量组疗效均优于小剂量组;免煎颗粒大剂量组的抗炎功效与传统饮片小剂量组相当。结论金叶败毒方之免煎颗粒具有与传统饮片相同的抗炎与增强免疫功能的功效,适当增加其剂量可望达到与传统饮片同等强度的治疗效应。     

超微生物钙颗粒剂毒理学实验

背景与目的 :检测超微生物钙颗粒剂作为保健食品的安全性。材料与方法 :小鼠经口急性毒性、二项致突变试验(小鼠骨髓嗜多染红细胞微核试验、小鼠精子畸形试验)以及30d喂养实验。结果 :超微生物钙颗粒剂对两种性别的SPF级昆明种小鼠经口毒性,一次灌胃量达10g/kg,两周内动物未见明显中毒症状,无动物死亡,按急性毒性分级标准规定,该受试物属实际无毒级。二项致突变试验结果均为阴性。30d喂养试验结果表明:该受试物对雌性大鼠低、中、高剂量为1.71、3.35、6.82g/kg剂量(分别相当于人群推荐量的26、50、102倍) ,对雄性大鼠低、中、高剂量为1.82、3.48、6.99g/kg(分别相当于人群推荐量的27、52、105倍)对Wistar大鼠的临床检查、血液学、生化学、脏器重量和系数以及病理组织学等指标无明显影响 ,未发现该受试物有明显的毒性作用。结论 :超微生物钙颗粒剂作为保健食品是安全的