低氧引起大鼠心室肌肌球蛋白重链图谱的变化

模拟5000米海拔高度低氧对大鼠心室肌肌球蛋白重链图谱的影响已作研究。用PP/PAGE,心室肌显示3种同功肌球蛋白,即V_1、V_2和V_3。在幼鼠中,V_1占优势,随着年龄的增长,V_3含量逐渐增加。用SDS/PAGE肌球蛋白呈双带、即MHCa和MHCβ,比较低氧与常氧条件下大鼠的心室肌MHCα与MHCβ的相对含量,我们发现低氧适应引起大鼠心室肌肌球蛋白重链图谱的变化,MHCα下降,MHCβ上升;MH邻的增加程度,右心室肌高于左心室。这提示低氧可能激活大鼠心肌编码肌球蛋白β重链的基因。     

蛋白转导结构域介导乙型肝炎病毒聚合酶末端蛋白重链可变区抗体体外抑制病毒的复制

目的 蛋白转导结构域(TAT)介导HBV聚合酶末端蛋白(TP)重链可变区(VH)抗体,研究特异性TAT-VH抗体体外对HBV复制的影响.方法 将TAT-VH基因克隆入原核表达载体pET28a(+),在大肠埃希菌BL21(DE3)LysS内诱导融合蛋白表达并进行纯化.纯化的TAT-VH加入培养的HepG2.2.15细胞,间接免疫荧光法检测其导入HepG2.2.15细胞的效率,四甲基偶氮唑盐(MTT)法检测其对细胞生长代谢的影响,将TAT-VH加入培养的HepG2.2.15细胞,定量PCR法检测HBV DNA水平.数据行单因素方差分析和t检验.结果 成功制备了TAT-VH融合蛋白,间接免疫荧光及MTT证实TAT-VH可以跨膜导入HepG2.2.15细胞,且对细胞生长无影响;加入5 000 nmol/L TAT-VH的HepG2.2.15细胞培养上清液内HBV DNA为(1.211±0.132)lg拷贝/mL,对照组为(5.325±0.041)lg拷贝/mL(t=72.91,P＜0.05);细胞内分别为(3.521±0.411)和(8.532±0.132)Ig拷贝/mL(t=28.41,P＜0.05).结论 HBV聚合酶TP区特异性TAT-VH抗体在体外可抑制HBV复制,为应用细胞内抗体治疗HBV感染提供了良好的实验基础.     

Preliminary enquiry into the availability, price and quality of malaria rapid diagnostic tests in the private health sector of six malaria-endemic countries

Objectives This enquiry aimed to provide a snap‐shot of availability, price and quality of malaria rapid diagnostic tests (RDTs) in private health facilities at selected sites in six malaria‐endemic countries in Africa, South East Asia and South America. Methods In each study site, data collectors surveyed private healthcare facilities which were selected based on accessibility from their home institution. Using a questionnaire, information was recorded about the facility itself and the malaria RDT(s) available. Where possible, a small number of RDTs were procured and quality control tested using a standardized procedure. Results Of the 324 private healthcare facilities visited, 35 outlets (mainly private clinics and hospitals) were found to supply 10 different types of RDTs products. RDT prices across the six countries ranged from US$1.00 to $16.81. Five of the 14 malaria RDTs collected failed quality control testing. Conclusions In the private outlets sampled, the availability of RDTs was limited. Some of the RDTs whose quality we tested demonstrated inadequate sensitivity. This presents a number of risks. Given the more widespread distribution of antimalarials currently planned for private sector facilities, parasite‐based diagnosis in this sector will be essential to adhere to the WHO guidelines for effective case management of malaria. Considerable regulation and quality control are also necessary to assure the availability of accurate and reliable RDTs, as well as adequate case management and provider adherence to RDT results. Public sector engagement is likely to be essential in this process.     

合肥市大蜀山几种药用植物体内铅的含量分析

目的:以安徽省合肥市郊大蜀山几种常见的药用植物为例,分析铅(Pb)在药用植物不同部位的分布,初步探索Pb在药用植物体内分布的规律。方法:采用湿法消化、原子吸收分光光度法测定Pb元素的含量。结果:植物体内Pb的含量与植物种类和生长环境有关。本实验为从源头控制中药材和中成药重金属超标提供科学依据。     

Mortality Risks Associated with Average Drinking Level and Episodic Heavy Drinking

Data from the 1997 to 2004 National Health Interview Survey Sample Adult questionnaires were linked to the National Death Index (N = 242,397) to examine mortality risks associated with average and episodic heavy drinking. Cox proportional hazard models (Stata 12.0) revealed that (average) heavier drinkers and episodic heavy drinkers (5+ in a day) had increased mortality risks but when examined together, episodic heavy drinking added only modestly to the mortality risks of light and moderate drinkers. Limitations and implications of results for survey measurement of potentially harmful levels of alcohol use are noted. This was a Federal study that received no outside funding.     

Initial,habitual and compulsive alcohol use is characterized by a shift of cue processing from ventral to dorsal striatum

Aims During the development of drug addiction, initial hedonic effects decrease when substance use becomes habitual and ultimately compulsive. Animal research suggests that these changes are represented by a transition from prefrontal cortical control to subcortical striatal control and within the striatum from ventral to dorsal domains of the striatum, but only limited evidence exists in humans. In this study we address this hypothesis in the context of alcohol dependence. Design, setting and participants Non‐abstinent heavy social drinkers (n = 21, 5.0 ± 1.5 drinks/day, 13 of them were alcohol‐dependent according to DSM‐IV) and light social drinkers (n = 10, 0.4 ± 0.4 drinks/day) were examined. Measurements We used a cue‐reactivity functional magnetic resonance imaging (fMRI) design during which pictures of alcoholic beverages and neutral control stimuli were presented. Findings In the dorsal striatum heavy drinkers showed significant higher activations compared to light drinkers, whereas light social drinkers showed higher cue‐induced fMRI activations in the ventral striatum and in prefrontal areas compared to heavy social drinkers [region of interest analyses, P < 0.05 false discovery rate (FDR)‐corrected]. Correspondingly, ventral striatal activation in heavy drinkers correlated negatively with obsessive‐compulsive craving, and furthermore we found a positive association between cue‐induced activation in the dorsal striatum and obsessive‐compulsive craving in all participants. Conclusions In line with our hypothesis we found higher cue‐induced activation of the ventral striatum in social compared to heavy drinkers, and higher dorsal striatal activation in heavy drinkers. Increased prefrontal activation may indicate that social drinkers activate cortical control when viewing alcohol cues, which may prevent the development of heavy drinking or alcohol dependence. Our results suggest differentiating treatment research depending on whether alcohol use is hedonic or compulsive.     

A Multi-Method Approach to Assess the Self-Interaction Behavior of Infliximab

Attractive self-interaction processes in antibody formulations increase the risk of aggregation and extraordinarily elevated viscosity at high protein concentrations. These challenges affect manufacturing and application. This study aimed to understand the self-interaction process of Infliximab as a model system with pronounced attractive self-interaction. The association mechanism was studied by a multi-method approach comprising analytical ultracentrifugation, dynamic light scattering, small angle X-ray scattering, self-interaction bio-layer interferometry and hydrogen-deuterium exchange mass spectrometry. Based on our results, both Fab and Fc regions of Infliximab are involved in self-interaction. We hypothesize a mechanism based on electrostatic interactions of polar and charged residues within the identified areas of the heavy and the light chain of the mAb. The combination of fast and reliable screening methods and low throughput but high resolution methods can contribute to detailed characterization and deeper understanding of specific self-interaction processes.