VX-induced cell death involves activation of caspase-3 in cultured rat cortical neurons

Exposure of cell cultures to organophosphorous compounds such as VX can result in cell death. However, it is not clear whether VX-induced cell death is necrotic or involves programmed cell death mechanisms. Activation of caspases, a family of cysteine proteases, is often involved in cell death, and in particular, caspase-3 activation appears to be a key event in programmed cell death processes including apoptosis. In this study, we investigated VX-induced neuronal cell death, as well as the underlying mechanism in terms of its effect on caspase-3 activity. Primary cortical neuronal cultures were prepared from gestational days 17 to 19 Sprague Dawley rat fetuses. At maturation, the cells were treated with varying concentrations of VX and cell death was evaluated by lactate dehydrogenase (LDH) release. VX induced an increase in LDH release in a concentration-dependent manner. Morphological VX-induced cell death was also characterized by using nuclear staining with propidium iodide and Hoechst 33342. VX induced a concentration- and time-dependent increase in caspase-3 activation. Caspase-3 activation was also confirmed by the proteolytic cleavage of poly(ADP-ribose)polymerase (PARP), an endogenous caspase-3 substrate. These data suggested that in rat cortical neurons, VX-induced cell death via a programmed cell death pathway that involves changes in caspase-3 protease.     

复方中药注射液对小白鼠艾氏腹水癌细胞膜表面的(Na~+-K~+)-ATP酶和微绒毛影响的电镜观察

本实验应用电镜细胞化学和扫描电镜技术,观察到小白鼠艾氏腹水癌细胞在复方中药注射液的连续作用下,膜表面(Na~+-K~+)-ATP酶活性减弱,微绒毛减退等变化,同时观察到该复方中药注射液对癌细胞增殖的抑制作用,抑瘤率可达87%,癌细胞增殖和(Na~+-K~+)-ATP酶活性及微绒毛的多少有平行关系。讨论了该复方中药抑制癌细胞增殖与膜表面(Na~+-K~+)-ATP酶活性和微绒毛变化的关系。     

Bloom's syndrome. XIX. Cytogenetic and population evidence for genetic heterogeneity

Cells with abnormally high rates of sister-chromatid exchange (SCE) are uniquely characteristic of Bloom's syndrome (BS). However, in one in five persons a minor population of cells with a low-SCE phenotype circulates in the blood. The origin and significance of the low-SCE cells in BS have never been understood, although they are assumed to arise by somatic mutation. In the present investigation, the enigmatic high-SCE/low-SCE mosaicism was investigated by comparing the incidence in several subpopulations of persons in the Bloom's Syndrome Registry who exhibit the two types of cells, and a striking negative correlation emerged: in persons with BS whose parents share a common ancestor, the case in approximately half of registered persons, low-SCE cells are found only rarely; conversely, the mosaicism occurs almost exclusively in persons with BS whose parents are not known to share a common ancestor. Because those who share a common ancestor are predominantly homozygous-by-descent at the mutated BS locus, the negative correlation is interpreted to mean that the emergence of low-SCE cells in BS in some way depends on the pre-existence of compound heterozygosity. A corollary to this is that BS is genetically heterogeneous.     

Experimental neurotoxicity of the anorectic fenfluramine

Summary Fenfluramine, an amphophilic compound which is a halogenated derivative of amphetamine, is still used as an anorectic agent for weight reduction, as it acts on the satiety center of the hypothalamus. Holtzman strain rats aged 6 days were daily injected s.c. fenfluramine hydrochloride at the dose of 75 mg/kg body weight. The animals were killed at different time intervals between days 7 and 40, and different parts of the brain were examined by light and electron microscopy. About half of the animals showed intralysosomal membrano-cytoplasmic bodies in the oligodendroglia, neurons, and neuropil, maximally in the animals receiving 8–19 injections. They were seen as concentrically arranged, single-layered lamellae; small dense bodies; or larger heterogeneous bodies. The mechanism of production of such inclusions could be the formation of complexes of this amphophilic compound with tissue phospholipids, or some enzyme-inhibiting action. A marked prominence of dark cells, predominantly oligodendroglia, was also noticed in the brains of experimental animals. Some of these cells appeared to be dark neurons, probably resulting from the serotonin-depleting effect of fenfluramine. A few dark cells were identified as resting microglial cells, while macrophagic reactive microglia were detected in the brains of very young animals. Fenfluramine appears to provide a model for studying neuroglial reactions.Paper presented at the Erwin Riesch symposium on Lysosomal Disorders of the Nervous System, Berlin (Convenor, Prof. Cervos-Navarro); and as poster-talk at the 9th International Congress of Neuropathology, Vienna, September 1982     

补肾益智方治疗阿尔兹海默病的研究进展

阿尔茨海默病（AD）是最常见的痴呆形式,目前缺少疾病修饰性的治疗药物。中医理论认为肾精亏虚是AD发生发展的内在机制,补肾益精是中医治疗AD的基本原则,贯穿AD治疗的始终。补肾益智方是治疗AD的临床经验方。补肾益智方治疗AD已有大量文献报道,但补肾益智方缺乏临床应用安全性评价,同时其基础研究薄弱,有效成分不明、多靶点作用机制不清。为阐明补肾益智方多成分、多靶点、多途径治疗AD的作用机制,该文综述了补肾益智方治疗AD的研究进展。进一步收集了16个基于高效液相色谱指纹图谱的补肾益智方主要化学成分,并对其成药性与安全性进行评价。利用基于AD重要病理生理学过程的网络药理学与文献综述相结合的方法,深入分析了补肾益智方靶向胆碱能系统、AD神经病理学特征的有效成分及可能机制。该研究为AD对症治疗、疾病修饰性治疗的药物研发提供了一系列有潜力的先导化合物,并为深入拓展补肾益智方的临床应用提供了理论依据。     

一种复合微生物菌肥对穿心莲生长、品质及土壤性质的影响

目的：研究一种微生物复合菌肥对穿心莲生长、品质及土壤性质的影响,旨在为穿心莲栽培生产中微生物复合菌肥的应用提供依据。方法：通过盆栽的共5个处理试验,CK（不施肥）组、A处理（施化肥）组、B处理（施微生物菌肥,施用量为2.5 g·kg-1土）组、C处理（施微生物菌肥,施用量为7.5 g·kg-1土）组、D处理（施微生物菌肥,施用量为12.5 g·kg-1土）组,研究一种复合微生物菌肥对穿心莲的农艺性状、有效成分含量及根际土壤细菌、放线菌、真菌的数量和土壤理化性质的影响。结果：施加一定量的复合微生物菌肥,穿心莲的株高、叶片数、叶面积、地上部、地下部鲜重较CK组和A处理组显著升高,不同生长期有差异。复合微生物菌肥对穿心莲内酯、脱水穿心莲内酯、新穿心莲内酯及14-去氧穿心莲内酯含量影响有差异,与CK组、A处理组比较,C处理组的穿心莲内酯分别明显升高26.13%、13.23%(P<0.05);新穿心莲内酯的含量随微生物菌肥施加量的增加而增加,在D处理组下的效应最显著,与CK组、A处理组比较,分别明显升高9.06%、50.33%(P<0.05);B处理组的14-去氧穿心莲内酯较A处理组...     

双—对二甲氨基苯甲醛缩二胺类希夫碱合成、表征及抗菌活性

目的：合成双－对二甲氨基苯甲醛缩二胺类希夫碱,并对其抗菌活性进行研究。方法：以对二甲氨基苯甲醛和二胺类为原料,经缩合反应,制得4种相应希夫碱。结果：结构经元素分析、红外光谱、核磁共振谱确定,4种化合物均未见文献报道,抗菌活性测试表明,它们具有一定抗菌活性。结论：乙酸是催化剂,对缩合反应有利,希夫碱化合物具有一定抗菌活性。     

葛根黄豆苷元分散片的制备及其溶出度测定

对葛根黄豆苷元片进行工艺改进,制成分散片,以提高其溶出度,并通过探讨葛根黄豆苷元片溶出度检查方法的稳定性、均一性、重现性、回收率试验等,确立测定葛根黄豆苷元片溶出度的最佳条件。     

高效液相色谱法考察复方头孢氨苄胶囊的溶出度

采用反相高效液相色谱外标法,对复方头孢氨苄胶囊溶出度进行考察。方法：采用转篮法,以4％乙酸溶液为溶剂,转速为100r/min,时间为45min。色谱条件：C18反相谱柱为固定相,V（水）：V（甲醇）：V(3．86％乙酸钠溶液）：V(4％乙酸溶液）＝742：240：15：3为流动相,流速为1.2mL/min,紫外检测波长为254nm,在此条件下头孢氨苄淀两组分能很好地分离。本法的线性范围分别是头孢氨苄为：27．6－276μg/mL,甲氧苄啶为：5．56－ 55．6μg/mL,平均回收率为头孢氨苄：99．32％,RSD＝0．78％;甲氧苄啶：100．1％,RSD＝0．57％。     

复方洗必泰滴眼液治疗真菌性角膜炎的临床研究

目的　探讨复方洗必泰滴眼液对真菌性角膜炎的治疗作用。方法　将真菌性角膜炎患者 65例68眼分为两组 ,每组 34眼 ,实验组用复方洗必泰滴眼液点眼。对照组用 0 .3%二性霉素B溶液滴眼治疗 ,并且回顾研究以前接治的未采用以上两法治疗的 30例病人的情况。疗效观察比较 ,所获数据经 χ2 检验。结果　实验组有效率 82 .35% ,阳性对照组有效率 67.65% ,卡方检验 ,P <0 .0 5,有统计学差异 ;回顾以前病人有效率 4 0 % ,与实验组比较 ,P <0 .0 0 5,差异显著。结论　复方洗必泰滴眼液可以作为临床抗真菌性角膜炎的一线局部用药 ,其疗效明显高于二性霉素B及其它传统药物治疗效果。