Modulation of paired-pulse responses in the dentate gyrus: effects of prenatal protein malnutrition

Since our major hypothesis is that prenatal protein malnutrition significantly affects hippocampal neuroplasticity, this study examined the effects of prenatal protein malnutrition on the modulation of dentate granule cell excitability in freely moving rats at 15, 30 and 90 days of age across the vigilance states of quiet waking (QW), slow-wave sleep (SWS) and rapid eye movement (REM) sleep. Using paired-pulse stimulation, the paired-pulse index (PPI), a measure of the type and degree of modulation of dentate granule cell excitability elicited by stimulation of the medial perforant path, was obtained for each vigilance state at each stage of development. Four specific measures of granule cell excitability were computed, namely, PPI using both population spike amplitude (PSA) and EPSP slope measures, absolute values of PSA(1) and EPSP(1) slope. PPI values obtained at 15, 30 and 90 days of age, however, were altered during normal ontogenetic development, but not by vigilance state. At 15 days of age, the malnourished group exhibits greater early inhibition of the PPI using the PSA measure at IPIs between 20 and 30 ms regardless of vigilance state, while at 30 days of age, the malnourished group exhibits greater facilitation at IPIs between 50 and 70 ms during QW and SWS, but not during REM sleep. In the control adult (PND90) and juvenile (PND30) animal, PSA(1) values are significantly higher during SWS than in QW or REM sleep. However, for the younger malnourished animals (PND15 and PND30), PSA(1) values were found to be significantly greater during REM sleep rather than SWS. Therefore, as the animal matures, there appears to be a shift in vigilance state dependent synaptic transmission through the hippocampal trisynaptic circuit from REM sleep to SWS in both control and malnourished animals, with the change occurring later in malnourished animals when compared to control ones. Furthermore, our findings suggests that prenatal protein malnutrition significantly alters modulation of dentate granule cell excitability (i.e., PPI values using the PSA measure) during the earlier stages of development but not in adulthood.     

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.     

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。     

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     

开郁清胃颗粒对2型糖尿病胰岛素敏感性的影响

目的：通过临床观察初步探讨开郁清胃颗粒对2型糖尿病患者胰岛素敏感性的影响。方法：以二甲双胍为对照，观察60例2型糖尿病患者治疗前后体重及腰臀围、症状积分、血糖、胰岛素、胰岛素敏感指数、血脂、焦虑及抑郁积分等指标的变化。结果：开郁清胃颗粒对2型糖尿病患者的血糖、血脂紊乱有明显的改善作用，并能减轻体重，提高胰岛素敏感性，改善焦虑及抑郁状态。结论：开郁清胃颗粒增加2型糖尿病患者的胰岛素敏感性可能与改善血脂紊乱，改善焦虑、抑郁状态及减轻体重等有关。     

补肾明目冲剂抗氧化作用实验研究（Ⅱ）

探讨补肾明目冲剂处缓和预防机体组织细胞生理衰老的机理。方法：选用自然衰老的１６月龄Ｗｉｓｔａｒ大鼠，用补肾明目冲剂灌胃３０天，维生素Ｅ为阳性对照组，灌胃结束后，取大鼠心，脑，晶状体蛋白和视网膜脉络膜组织。用丙二醛法测定脂质过氧化物含量；用亚硝酸盐试剂盒检测超化物歧化酶活性；用ＤＴＮＢ法测定谷光甘肽过氧化物酶活性；用钼酸铵显色法测定过氧化氢酶活性；用Ｓｃｈｉｆｆ碱荧光法测定脂褐素含量。     

高效液相色谱法同时测定根痛平冲剂中芍药甙和葛根素的含量

采用反相高效液相色谱法，建立了一种可同时测定根痛平冲剂中芍药甙和葛根素含量的方法。芍药甙和葛根素的平均回收率分别为９９．１１％，９７．８４％；ＲＳＤ分别为１．８３％，１．９１％。该法快速、准确，操作简便，可用于产品的质量控制。