甲型肝炎病毒(HAV)感染普通狨猴的病理学观察

观察使用ＨＡＶ疫苗株和野毒株感染普通狨猴后引起的病理变化，并对病变作分级描述。结果显示，疫苗株感染的狨猴未见异常，而野毒株致全部动物肝脏出现甲肝病变     

TNT灌胃在恒河猴体内的毒物代谢动力学研究

用120mg/kgTNT给恒河猴一次灌胃染毒,血中TNT、DNAT和MHb的浓度—时间曲线均符合单室模型。TNT和DNAT均呈现吸收较快、消除较慢的特点。血中峰浓度和曲线下面积,DNAT均为TNT的37倍,全血廓清率DNAT为TNT的1/40,表观分布容积DNAT为TNT的1/50。椐主要动力参数比较,DNAT比TNT更接近MHb。结果表明,DNAT可用于TNT接触的生物监测。     

恒河猴的血清蛋白质电泳及其与人类、家猪的比较研究

[目的]恒河猴(Macaca mulatta)是异种移植研究和药物临床前评价中最重要的动物模型.为了探索临床前研究与临床应用的差距的可能原因,初步研究了恒河猴的血清蛋白质. [方法]分别采集36只正常恒河猴(成都平安动物繁育基地)、30只正常香猪(贵州大学农学院养殖场)和46个正常人(华西医院)的静脉血,采用REP电泳系统电泳血清蛋白.结果采用SPSS 12.0统计学软件分析. [结果]猴血清蛋白中的Alb百分含量比人的低、而比猪的高(P<0.05),Alpha1、Alpha2百兮含量比人的高、而比猪的低(P<0.05),Beta百分含量比猪和人的都低(P<0.05),Gamma百分含量比猪的低(P<0.05). [结论]结果显示了猴与人、猪在血清蛋白组分上都存在着一定的差异.这些差异可能会致在猴体内连行的药物临康前研究结果与在人体内的真实情况不符,从而影响药物的临床应用价值和安全性评价;也可能是猪到猴或猪到人的异种移植中生物功能不匹配的潜在原因,而猴和人的差异也可能影响异种移植后的监测和对排斥强度的估计.     

低剂量铅间断性染毒对恒河猴慢性毒性和自然恢复的影响

本文以较低剂量(5和20mg/kg)的醋酸铅对恒河猴进行重复二次染毒,实验结果表明,动物中毒表现不明显,但铅特异指标如PbB、FEP、ZnPP和δ-ALAD等含量已发生明显的改变。血清钙含量在染毒前、后无显著差异。两次染毒猴子对铅的吸收速率基本一致,第二阶段染毒停止后PbB水平恢复要慢于第一阶段,提示铅蓄积随染毒时间、频率而增加。在本实验剂量下,主要引起机体铅蓄积和铅接触指标的变化。此外,由于长期接触尚可能造成部分脏器的功能异常。     

Bax和Bcl-2在恒河猴正常妊娠和药物流产胎盘组织中的表达研究

目的:Bax和Bcl-2是重要的凋亡调节因子,本研究主要探讨细胞凋亡与流产的关系。方 法:应用RT-PCR和原位杂交的方法检测恒河猴正常妊娠和药物流产胎盘、子宫中Bax和Bcl-2的 表达。结果:BaxmRNA在流产胎盘中的表达量明显高于正常妊娠胎盘,在胎盘绒毛滋养层细胞和基 底层蜕膜细胞均有明显表达。Bcl-2mRNA在流产胎盘中的表达量明显低于正常妊娠胎盘,表达模 式与Bax类似。结论:药物可能通过上调Bax和下调Bcl-2的表达,导致恒河猴胎盘组织和子宫基 底层凋亡细胞的数量增加,影响胎盘的正常结构和功能,从而增加了流产的危险性。     

血管新生调节因子VEGF及其受体在恒河猴正常妊娠和药物流产胎盘中的表达

目的:研究血管新生调节因子VEGF及其受体Flt-1、KDR在恒河猴正常妊娠和药物流产胎盘组织中的表达。方法:用免疫组化方法检测妊娠30天的恒河猴上述蛋白在胎盘中的表达。结果:VEGF蛋白主要表达于胎盘绒毛和子宫内膜,在母胎界面和子宫内膜血管中显著高表达;KDR蛋白的表达模式与VEGF类似;Flt-1蛋白在两组胎盘中的表达无显著差异。VEGF和KDR在药物流产胎盘中的表达量明显低于正常妊娠胎盘。结论:VEGF、Flt-1及KDR在恒河猴妊娠早期参与子宫内膜和胎盘发育过程中的血管新生,在胎盘绒毛的浸润以及腺上皮细胞分化及其分泌等过程中也发挥着重要作用;流产药物可能通过下调VEGF和KDR蛋白的表达,影响了血管发生和胎盘发育,增加了流产机会。     

甲型肝炎病毒变异及其生物学意义

甲型肝炎病毒(HAV)变异的研究将有助于阐明其根本的生物学行为、HAV复制和繁殖效率、毒力和免疫原性的强弱及致病机制,也为HAV体外培养的适应、减毒、疫苗研制及其安全性评价提供分子生物学依据,并有利于HAV分子流行病学的研究。本文对近年来HAV各基因结构区的变异及其相关生物学意义的研究进展作了综述。     

饮用水中甲型肝炎病毒灭活研究

用ＰＬＣ／ＰＲＦ／５肝癌细胞培养甲型肝炎病毒（ＨＡＶ），用ＥＬＩＳＡ方法检测经细胞培养增殖病毒的方法，进行评价氯灭活水中ＨＡＶ的效果。实验结果表明，甲型肝炎病毒对氯的抗力比大肠杆菌强，在脱氯自来水中加入ＨＡＶ，氯投加量３．０ｍｇ／Ｌ，接触５～３０ｍｉｎ，余氯１．１ｍｇ／Ｌ，才能灭活水中的ＨＡＶ。而用氯胺消毒，必须达１５ｍｇ／Ｌ，接触时间５～３０ｍｉｎ，才能灭活水中的ＨＡＶ。     

甲肝病毒的核苷酸变异研究

[目的]揭示甲肝病毒在甲肝疫苗使用多年后的变异情况。[方法]用逆转录(RT)、PCR、套式PCR(nPCR)扩增来自病人血清中的甲肝病毒和甲肝疫苗H2减毒株的5’端非编码区中的核苷酸片段。扩增的片段进行核酸序列测定，并与甲肝疫苗H2减毒株的相应序列进行比较。[结果]从22份RT-PCR-nPCR甲肝病人血清中扩增到3个目的片段，经测序比较，其中两个扩增片段的序列与甲肝疫苗株的相应序列一致，另一扩增片段的序列与甲肝疫苗株的相应序列比较有一个核苷酸的变异。[结论]甲肝病毒在甲肝疫苗使用多年后没有变异。     

氯灭活水中甲型肝炎病毒指示微生物的实验研究

为研究氯灭活水中甲型肝炎病毒的指示微生物，用组织培养的ＨＡＶ污染水样，用游离氯进行灭活，同时与氯灭活水中大肠杆菌，大肠杆菌噬菌体ｆ２、脊髓灰质炎病毒效果进行比较。结果表明氯灭活蒸馏水中各微生物的浓－时（Ｃ－Ｔ）积分别为１０．００、０．８５、４．３７、１２．８１；灭活脱氯自来水中各微生物的Ｃ－Ｔ积分另为１５．００、７．８５、１２．４８、２９．９９，故认为ＰＶ１可作为氯灭活水中ＨＡＶ的指示微生物。     

蚊虫人工感染乙型肝炎病毒的实验观察

本文介绍1982年用实验室饲养的致乏库蚊进行人工感染HBsAg阳性血。逐日采蚊用RPHA、ELISA、SPRIA三种方法检测，发现蚊虫携带HBsAg与蚊胃血消化有关。蚊虫吸血后1~4天内可检出HBsAg，血液消化后HBsAg也消失。HBsAg阳性蚊的排泄物、卵、幼虫、蛹及第一代雌、雄蚊均未检出HBsAg。说明吸血蚊的传播乙型肝炎病毒的作用，可能是通过机械性传播，而蚊虫不是媒介宿主。     

Prevalence of Balantidium coli Infection in Bred Rhesus Monkeys (Macaca mulatta) in Guangxi,southern China

Background

Balantidium coli infects humans, primates and pigs, causing serious diarrhea and dysentery. Little information on the prevalence of B. coli in primates is available in China. This investigation was conducted to determine the prevalence of B. coli infection in bred rhesus monkeys in Guangxi Zhuang Nationality Autonomous Region (GZNAR), southern China.

Methods

A total of 120 fecal samples were collected from rhesus monkeys bred in cages in GZNAR and B. coli cysts and/or trophozoites were examined microscopically after sedimentation with water in May 2013.

Results

(64.2%) samples were tested positive. The prevalence was 65% (39/60) and 63.3% (38/60) in female and male monkeys, respectively. 80% (48/60) cages in this nonhuman primate center were positive for B. coli.

Conclusion

The present survey revealed high circulation of B. coli in bred rhesus monkeys in GZNAR, which poses potential threats to animal and human health.     

甲型肝炎病毒TZ84株单克隆抗体在甲型肝炎抗体检测中的应用

将不同位点的甲型肝炎 (甲肝 )病毒 (HAV)TZ84单克隆抗体 (单抗 )或酶标单抗进行混合做包被和酶 ,代替现有试剂中的多克隆抗体 (多抗 ) ,采用竞争抑制法对试剂的灵敏度和可靠性进行测定 ,并通过 2 2 9份甲肝灭活疫苗临床观察血清甲肝病毒抗体的检测 ,对单抗试剂的应用进行研究 ,并对该单抗试剂进行评价。结果表明 :该单抗试剂的灵敏度为 94 % ,特异度均为 98% ,最低检出浓度的变异系数为 9 3% ;单抗试剂、多抗试剂和雅培试剂的最低检出浓度分别为 5 5、98、31mIU/ml。单抗试剂的灵敏度高于多抗试剂 ,特异度低于多抗试剂。     

Similarity of Bisphenol A Pharmacokinetics in Rhesus Monkeys and Mice: Relevance for Human Exposure

Objective

Daily adult human exposure to bisphenol A (BPA) has been estimated at < 1 μg/kg, with virtually complete first-pass conjugation in the liver in primates but not in mice. We measured unconjugated and conjugated BPA levels in serum from adult female rhesus monkeys and adult female mice after oral administration of BPA and compared findings in mice and monkeys with prior published data in women.

Methods

Eleven adult female rhesus macaques were fed 400 μg/kg deuterated BPA (dBPA) daily for 7 days. Levels of serum dBPA were analyzed by isotope-dilution liquid chromatography–mass spectrometry (0.2 ng/mL limit of quantitation) over 24 hr on day 1 and on day 7. The same dose of BPA was fed to adult female CD-1 mice; other female mice were administered ³H-BPA at doses ranging from 2 to 100,000 μg/kg.

Results

In monkeys, the maximum unconjugated serum dBPA concentration of 4 ng/mL was reached 1 hr after feeding and declined to low levels by 24 hr, with no significant bioaccumulation after seven daily doses. Mice and monkeys cleared unconjugated serum BPA at virtually identical rates. We observed a linear (proportional) relationship between administered dose and serum BPA in mice.

Conclusions

BPA pharmacokinetics in women, female monkeys, and mice is very similar. By comparison with approximately 2 ng/mL unconjugated serum BPA reported in multiple human studies, the average 24-hr unconjugated serum BPA concentration of 0.5 ng/mL in both monkeys and mice after a 400 μg/kg oral dose suggests that total daily human exposure is via multiple routes and is much higher than previously assumed.     

Physicians' assessments of the utility of health states associated with Human Immunodeficiency Virus (HIV) and Hepatitis B Virus (HBV) Infection

An understanding of quality of life (QOL) with human immunodeficiency virus (HIV) is important because the merits of prevention and treatment alternatives may depend substantially on how these interventions affect QOL. Physicians' views about QOL are important, because they influence the therapeutic options that physicians consider or offer, the recommendations that physicians make, and because they are important for the analysis of certain policy questions. We assessed physicians' utilities of health states associated with HIV infection, and hepatitis B virus (HBV) infection; assessment of utilities for HBV was included to provide a comparison with HIV utilities. We surveyed 200 housestaff and staff physicians in an academic medical centre by anonymous paper-based questionnaire and used the time-tradeoff method to assess physicians' utilities of the health states. On a scale in which 0 was equivalent to death, and 1 was equivalent to good health, the median utilities for asymptomatic HIV infection, symptomatic HIV infection, and AIDS were 0.833, 0.417, and 0.167, respectively (p < 0.01 for each two-way comparison). Median utilities for asymptomatic HBV infection, mildly symptomatic HBV infection, and severely symptomatic HBV infection were 0.917, 0.667, and 0.167, respectively (p < 0.01 for each two-way comparison). Although physicians varied substantially in the ratings of health states, they assessed the utility of life with HIV disease, including asymptomatic infection, as severely reduced. Studies of the effectiveness and cost-effectiveness of preventive and therapeutic interventions for HIV should evaluate the effect of the intervention on utility-based assessments of QOL. Studies that do not assess such effects may significantly underestimate or overestimate the value of these interventions, depending on the intervention's effect on QOL.     

深圳地区HEV流行基因型及动物宿主带毒状况分析

目的了解深圳地区戊型肝炎病毒(HEV)流行基因型及动物宿主带毒状况。方法通过同源比对HEV四种基因型的戊型肝炎病毒序列,选取其保守序列部分设计两对巢式聚合酶链式反应的简并引物,建立一种可同时扩增戊型肝炎四个基因型病毒RNA的PCR快速检测方法。对深圳市采集的80份猪粪便标本和6份戊型肝炎病人血清,提取病毒RNA,然后进行PCR检测,阳性时对扩增片段进行基因序列测定,并进行基因型分析。结果80份猪粪便标本5份HEV—RNA阳性,6份病人血清样本中4份阳性。序列分析显示全部为HEV基因IV型,5份猪标本中的HEV基因序列与GenBank中人HEV的基因序列最相似,同源性为88%～94%。结论深圳地区HEV流行株为基因IV型,而且猪HEV基因序列与人HEV之间有着高度的相似性,证实猪是HEV的宿主,戊型肝炎是一种人兽共患传染病。