TLR4参与脑缺血再灌注小鼠海马细胞凋亡

目的探讨Toll样受体4(TLR4)在小鼠脑缺血再灌注损伤中对细胞凋亡的影响。方法昆明小鼠90只,随机分为:假手术组、缺血再灌注组、TLR4抗体阻断组,每组依据缺血后再灌注6h、12h、24h、48h、72h不同时间点再分五个小组。采用免疫组织化学方法,Western blot方法检测Caspase-3在各组海马不同再灌注时间点的表达变化,应用TUNEL法检测海马细胞凋亡情况。结果缺血再灌注组Caspase-3蛋白表达量和凋亡细胞数明显高于假手术组(p<0.01),而TLR4阻断组Caspase-3蛋白表达量和凋亡细胞数则明显少于缺血再灌注组(p<0.01)。结论阻断TLR4可减少脑缺血再灌注损伤中的细胞凋亡。     

UCF-101对大鼠脑缺血再灌注损伤的神经保护作用

目的观察UCF-101对大鼠脑缺血再灌注损伤后神经元凋亡及Caspase-9蛋白表达的影响,探讨UCF-101对缺血性脑损伤的神经保护作用。方法随机将大鼠分为假手术组、缺血再灌注组及UCF-101处理组。采用线栓法建立Wistar大鼠大脑中动脉闭塞(MCAO)2h再灌注模型,于再灌注后24h取脑,采用TTC法测梗死体积,TUNEL法检测神经元凋亡,免疫组化法观察脑组织神经元Caspase-9蛋白的表达。结果假手术组未见梗死现象,与假手术组比较,缺血再灌注组脑组织凋亡细胞数和Caspase-9的表达均明显升高(P0.05)。与缺血再灌注组相比,UCF-101处理组梗死体积明显缩小(P0.05),UCF-101处理组脑组织凋亡细胞数和Caspase-9的表达均明显减少(P0.05)。结论 UCF-101可能通过下调脑组织神经元Caspase-9蛋白的表达,抑制神经元的凋亡而发挥神经保护作用。     

异丙酚对大鼠脑缺血再灌注海马细胞周期因子变化及神经元凋亡的影响

目的： 探讨大鼠局灶性脑缺血再灌注后海马神经元细胞周期蛋白1（cyclin D1）和细胞周期蛋白依赖性蛋白激酶4（cyclin-dependent kinase 4,CDK4）的表达与神经元凋亡的关系及异丙酚的脑保护作用。方法: 采用大脑中动脉内栓线阻断法（middle cerebral artery obstruction,MCAO）造成局灶性脑缺血再灌注模型。用免疫印迹法（Western blotting）观察cyclin D1和CDK4蛋白的表达;采用流式细胞仪检测海马神经元凋亡。再灌注48 h时进行大鼠神经功能缺陷比较。结果: （1）异丙酚可以改善大鼠脑缺血再灌注后的神经功能缺陷（P＜0.01）;（2）与假手术组比较,脑缺血再灌注48 h后缺血侧海马神经元cyclin D1、CDK4表达明显升高、凋亡细胞数明显增多（P＜0.01）。与缺血再灌注组比较,异丙酚组海马神经元cyclin D1、CDK4的表达和凋亡率明显降低（P＜0.05）。结论: 脑缺血再灌注后缺血侧海马cyclin D1、CDK4表达增强,这可能是介导脑缺血再灌注后神经元凋亡的机制之一;异丙酚可下调神经元cyclin D1、CDK4的表达,抑制神经元凋亡,减轻缺血再灌注对大鼠海马神经元的损伤。     

bFGF对局灶性脑缺血大鼠脑组织GRP78表达的影响

目的研究大鼠脑缺血再灌注后对葡萄糖调节蛋白78(glucose-regulated protein78,GRP78)表达的影响,探讨碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)对脑组织缺血再灌注神经元GRP78的调节作用及机制。方法应用线栓法制作大鼠局灶性脑缺血再灌注模型,大脑中动脉阻塞2h再灌注损伤12h,采用TUNEL法、免疫组化检测海马及皮质内神经元凋亡和GRP78的表达。结果 sham组,海马及皮质偶见凋亡细胞,皮质及海马神经元内少见GRP78免疫反应阳性细胞;I/R组,海马及皮质神经元凋亡增加,缺血再灌注损伤后皮质及海马神经元内GRP78阳性表达明显高于假手术组。bFGF组,海马及皮质神经元凋亡减少,皮质及海马神经元内GRP78表达较I/R组明显增加。结论 bFGF显著减少缺血神经元凋亡,上调脑缺血诱导的GRP78表达,对脑缺血再灌注海马及皮质神经元的具有保护作用。     

黄芪注射液对脑缺血再灌注大鼠海马神经元凋亡及JNK3表达的影响

目的:观察黄芪注射液对脑缺血再灌注大鼠海马神经元凋亡及c-Jun N末端激酶3(JNK3)表达的影响。方法:四血管阻断法制备脑缺血再灌注大鼠模型。设假手术组、脑缺血再灌注模型组(模型组)、脑缺血再灌注模型+黄芪注射液组(黄芪注射液组)和脑缺血再灌注模型+黄芪注射液溶剂对照组(溶剂对照组)。除假手术组外其余3组根据再灌注时间不同又分为0 h、0.5 h、2 h、6 h、24 h、72 h和120 h 7个亚组。采用TUNEL法检测海马神经元凋亡,Western blotting法检测海马组织JNK3蛋白变化,real-time PCR法检测海马组织JNK3 mRNA 的表达变化。结果:与假手术组比,模型组大鼠各个时点凋亡细胞数均增多(P<0.05);与模型组比,黄芪注射液组各个时点的细胞凋亡数明显减少(P<0.05),而黄芪注射液溶剂对照组各个时点的细胞凋亡数无明显变化(P>0.05)。除120 h外,模型组各时点海马组织JNK3蛋白及mRNA表达均较假手术组增加(P<0.05);与模型组相比,黄芪注射液可减弱除120 h之外的各时点JNK3 蛋白及mRNA的表达(P<0.05),而黄芪注射液溶剂对照组则无明显变化(P>0.05)。结论:黄芪注射液可抑制脑缺血再灌注大鼠海马神经元凋亡,其抗凋亡机制可能与下调JNK3 mRNA及蛋白表达有关。     

碱性成纤维细胞生长因子对局灶性脑缺血大鼠脑组织C/EBP同源蛋白表达的影响

目的:研究大鼠脑缺血再灌注后对C/EBP同源蛋白(C/EBP homogous protein,CHOP)表达的影响,探讨碱性成纤维细胞生长因子(bFGF)对脑组织缺血再灌注神经元CHOP的调节作用及机制.方法:应用线栓法制作大鼠局灶性脑缺血再灌注模型,大脑中动脉阻塞2h再灌注损伤12 h,采用TUNEL法、免疫组织化学方法检测海马及皮质内神经元凋亡和CHOP的表达.结果:Sham组海马及皮质偶见凋亡细胞,皮质及海马神经元内少见CHOP免疫反应阳性细胞;I/R组海马及皮质神经元凋亡增加,缺血再灌注损伤后皮质及海马神经元内CHOP阳性表达高于假手术组.bFGF组海马及皮质神经元凋亡减少,皮质及海马神经元内CHOP表达较I/R组减少.结论:bFGF减少缺血神经元凋亡,抑制脑缺血诱导的CHOP表达,对脑缺血再灌注海马及皮质神经元具有保护作用.     

重组人促红细胞生成素对脑缺血再灌注小鼠海马VEGF表达的影响

目的探讨重组人促红细胞生成素(recombinant human erythropoietin,rHuEPO)对脑缺血再灌注小鼠血管内皮生长因子(vascular endothelial growth factor,VEGF)表达的影响。方法 96只昆明小鼠随机分为3组,每组32只:假手术组(Sham);rHuEPO治疗组;缺血再灌注组(I/R)。每组依据缺血后再灌注不同时间点再分6h、24h、3d、7d五个小组。免疫组化和Westernblot检测各组小鼠VEGF的表达,TUNEL法检测海马细胞凋亡情况。结果缺血再灌注组海马VEGF蛋白表达量和凋亡细胞数明显高于假手术组(<0.05),与缺血再灌注组相比,rHuEPO治疗组VEGF蛋白表达量明显升高(<0.05),凋亡细胞数则明显少于缺血再灌注组(相似文献   

重组人促红细胞生成素对脑缺血再灌注小鼠海马IL-1β表达的影响

目的探讨重组人促红细胞生成素(recombinant human erythropoietin,rhEPO)对脑缺血再灌注小鼠白介素-1β(interleukin-1β,IL-1β)表达的影响。方法 96只昆明小鼠随机分为3组,每组32只:假手术组(Sham);rHuEPO治疗组;缺血再灌注组(I/R)。每组依据缺血后再灌注不同时间点再分6 h、24 h、3 d、7 d 5个小组。免疫组化和Western blot检测各组小鼠IL-1β的表达。TUNEL法检测海马细胞凋亡情况。结果缺血再灌注组IL-1β蛋白表达量和凋亡细胞数明显高于假手术组(P<0.05),而rhEPO治疗组IL-1β蛋白表达量和凋亡细胞数则明显少于缺血再灌注组(P<0.05)。结论 rHuEPO很可通过下调IL-1β的表达参与脑缺血再灌注损伤。     

UCF-101对大鼠脑缺血再灌注后凋亡抑制蛋白XIAP表达的影响

目的观察UCF-101对大鼠脑缺血再灌注损伤后神经元凋亡及凋亡抑制蛋白XIAP表达的影响,探讨UCF-101对缺血性脑损伤的神经保护作用。方法采用线栓法建立Wistar大鼠大脑中动脉闭塞(MCAO)2h再灌注模型,随机将大鼠分为假手术组、缺血再灌注组及UCF-101处理组,于再灌注后24h取脑,采用TTC法测梗死体积,TUNEL法检测神经元凋亡,免疫组化法观察脑组织神经元XIAP蛋白的表达。结果假手术组未见梗死现象,偶见凋亡神经细胞,神经元中可见棕黄色XIAP颗粒散在分布于核膜周围胞浆中。与假手术组比较,缺血再灌注组可见梗死灶,脑组织凋亡细胞数明显增加,XIAP的表达明显降低(P<0.05);与缺血再灌注组比较,UCF-101处理组梗死体积明显缩小(P<0.05),脑组织凋亡细胞数减少,XIAP的表达均明显增加(P<0.05)。结论 UCF-101神经保护作用可能与上调脑组织神经元XIAP蛋白的表达和抑制神经元的凋亡有关。     

姜黄素对大鼠脑缺血再灌注海马神经元凋亡及PI3K信号因子表达的影响

目的探讨姜黄素对大鼠脑缺血再灌注致海马神经元凋亡及PI3K信号通路相关因子表达的影响。方法采用线栓法阻塞SD大鼠大脑中动脉(MCAO),建立大鼠局灶性脑缺血/再灌注实验模型,将40只SD大鼠随机分为假手术组(S组)、缺血/再灌注组(I/R组)和姜黄素处理组(C组);各组于再灌注后24h,大鼠放血处死,取静脉血分离血清,ELISA检测血清中炎症因子IL-6,TNF-a及脑损伤标志物S-100β的变化;另取脑组织,一部分浸泡福尔马林,HE染色观察脑组织变化,TUNEL法观察脑组织细胞凋亡情况;采用Western blot法检测海马P-PI3K、Akt和Caspase-3蛋白表达变化。结果姜黄素可以减轻大鼠脑缺血再灌注致海马神经元凋亡,降低血清中IL-6、TNF-a、S-100β含量,抑制脑组织中caspase-3、PI3K和Akt蛋白表达水平(P0.05)。结论姜黄素减轻缺血再灌注导致的脑损伤可能与PI3K信号通路相关。     

Secular change in menarche in women in Madrid

The age at menarche was estimated by recollection in 1617 women between the ages of 18 and 60 in Madrid and a nearby suburb, Pinto. The population of Pinto is working-class and the Madrid group, taken from residential neighbourhoods , belongs to the upper middle class. In both groups we found a diminution in average age at menarche, from 14.04 to 13.02 years in Madrid and from 14.55 to 13.16 years from about 1935 to about 1965 in Pinto. These changes have been more intense in the group which is less well-off economically, where living conditions have varied much more drastically.     

Intestinal helminthiasis in school children in Haiti in 2002

A survey on intestinal helminths in school children was conducted in Haiti in 2002. This first nationwide study involving the entire country was stratified by department according to urban and rural zones using the cluster method. Focusing on elementary school children (n=5792; age range 3 to 20 years), it involved 26 urban and 49 rural schools randomly selected. Stools were preserved in formalin and examined by the Ritchie technique. Thirty-four per cent of stools (1981/5792) tested positive for intestinal helminths with the following parasites identified: Ascaris lumbricoides (27.3%), Trichuris trichiura (7.3%), Necator americanus (3.8%), Hymenolepsis nana (2%), Taenia sp. (0.3%) and Strongyloides stercoralis (0.2%). The helminth prevalence was higher in rural (38.4%) compared to urban areas (30%). There was no significant difference in prevalence by sex and age. The importance of geohelminths changed from one department to another with the highest prevalence found in the Southern department of Grande Anse (73.7%) and the lowest prevalence in the Center department (20.6%). Five out of the country's nine departments had a similar prevalence varying from 25.5% to 28.2%. Intestinal helminthic polyparasitism was observed in a percentage of infested school children comprise between 3.4% and 28.6% according in relation to the geographical area. A program to fight against geohelminths in school children should be initiated as a public health priority. Albendazole is the drug of choice. Frequency of drug distribution should be based on the prevalence of geohelminths in each department.     

Experience in adult population in dengue outbreak in Delhi

A dengue outbreak has recently hit the Indian capital. We studied the clinical profile of adult patients. Five hundred and sixty patients of dengue infection were admitted in a specially created ward according to the criteria laid down by WHO. Haematemesis (28.28%), epistaxis (26.78%) and malena (14.28%) were some of the common presentations. Similarly lymphadenopathy, especially cervical (30.89%), palatal rashes (26.96%) and hepatomegaly (23.75%) were the most commonly encountered findings on physical examination. Most of the cases were of dengue fever with haemorrhage and only 2.5% cases were classified under dengue haemorrhagic fever or dengue shock syndrome. The average hospital stay was 3.4 days but only 9.8 hours in the eleven patients who died, suggesting their late arrival in preterminal situation giving little time for resuscitation. Thrombocytopenia was not a feature and only 12.85% patients had platelet count less than 70,000/cmm. Most of the patients who were admitted with thrombocytopenia, showed normalization in their platelet counts in next few days. Serological examination demonstrated evidence of recent dengue infection in 41.17% patients. Few patients required blood or platelet concentrate transfusion. Eleven patients died, three due to DIC, one of intracranial haemorrhage and seven due to massive gastric haemorrhage. Rest of the patients recovered completely. Thus we can conclude that recent outbreak in Delhi was of dengue fever with haemorrhage and mortality was very low in patients who came early to the hospital.     

Changes in the hypothalamic nuclei in in experimental allergy

Summary In rabbits subjected to prolonged sensitization and in which the Arthus phenomenon was induced there was a marked reaction of the hypothalamic nuclei. Staining by Gomori's method indicated a cellular swelling, loss of granules, and protoplasmic vacuolization in the supraoptic nucleus. There was a considerable increase in the size of the cross-sectional area of the cells. The same effects were much less well shown in the paraventricular nucleus. These results show that marked signs of increased neurosecretion developed in the animals at the height of the Arthus phenomenon.(Presented by Active Member AMN SSSR V. V. Parin) Translated from Byulleten Éksperimental'noi biologii i Meditsiny, Vol. 55, No. 4, pp. 110–113, April, 1963.     

Development in in vitro toxicology

There are three principal pressures driving the development of in vitro toxicology: (1) the need for more efficient testing systems to cope with the large number of xenobiotics currently being developed; (2) public pressure to reduce animal experimentation; and (3) a need for a better understanding of the mechanisms of toxicity. Within this, in vitro toxicology is focused on local, systemic, and target-organ toxicity. It is becoming increasingly apparent that a step or decision-tree approach using input of a variety of experimental data (physicochemical properties, biokinetics, cytotoxicity) provides the most efficient system for predicting toxicity. Examples of the use of in vitro toxicity systems for prediction of systemic toxicity and target-organ (liver) toxicity are presented.Originally presented at ECCP 93.