HIV variability in the liver and evidence of possible compartmentalization

There is growing evidence to suggest that HIV may interact with several hepatic cell types; however, evaluation of HIV variability in liver tissue has not been addressed to date. Among 16 HIV-positive individuals examined, nine (56%) had detectable HIV RNA in the liver. The mean CD4 cell count for these nine individuals was 337 cells/mm(3) (range: 0-601), while their mean plasma HIV RNA level was 106,974 copies/ml (range: 1200-320,740). Among individuals in this study with detectable HIV in both the plasma and the liver, the consensus gag nucleotide sequences for each tissue type were different for seven of seven (100%) individuals, while amino acid sequences were distinct for five of seven (71%). Consensus envelope (env) nucleotide and amino acid sequences were also distinct in the plasma and liver tissue for six of six (100%) individuals. Statistical evidence of compartmentalization between HIV in the plasma and in the liver was demonstrated, and multiple liver-specific amino acids were identified that may distinguish HIV variants replicating within the liver. These preliminary data demonstrate that HIV is frequently detectable in the liver of HIV-positive persons at various levels of immunosuppression. Possible compartmentalization may reflect tissue-specific selection pressures that drive viral adaptation to the liver microenvironment and may facilitate interactions with other hepatotropic viruses.     

Knowledge and risk factors of intestinal parasitic infections among women in Makurdi,Benue State

ObjectiveTo assess women's perceptions and risk factors that could expose them to intestinal parasitic infections in Makurdi, Benue State, Nigeria.MethodsA total of 750 faecal samples were collected from women at different reproductive stages (pre-menstrual, menstrual and post-menstrual), and the faeces were tested by the formol ether concentration technique.ResultsA total of 426 (56.8%) samples were found positive for various intestinal parasites with hookworm (4.8%), Ascaris lumbricoides (9.3%), Taenia sp (2.1%), Entamoeba histolytica (18.9%) and Entamoeba coli (21.6%). Women at pre-menstrual and post-menstrual stages recorded higher prevalence rates with 72.8% and 63.9%, respectively. No significant difference in prevalence was observed between women at different reproductive stages and women infected by different parasites (χ² = 30.6, P > 0.05). Sweet things, rotten fruits and improperly cooked meat were perceived as the causes of intestinal parasitic infections among the pre and post menstrual women. Sources of drinking water like river, well, water bought from vendors and patronizing food vendors were observed as risk factors contributing to the prevalence of intestinal parasitic infections among women. Factors like not washing hands before eating and after defaecation, use of leaves and ordinary papers for cleaning after defaecation were also observed to be contributing to the prevalence of intestinal parasitic infections.ConclusionsPersuasive health education and rigorous hygiene measures should be employed in schools, maternity clinics and among the populace to reduce transmission and infection with intestinal parasites.     

血管成形术和支架辅助血管成形术治疗颅内动脉粥样硬化的报告标准（下）

本刊经Philip M．Meyers博士代表写作组授权,将“ Reporting standards for angioplasty and stent-assisted angioplasty for intracranial atherosclerosis”译为中文在本刊刊登。标准中对患者的选择、颅内动脉狭窄程度的判断、最佳内科治疗、围手术期处理、血管内治疗、术后并发症等,进行了规范化总结,拟为今后的临床试验和研究的规范化确定标准,以保证结果的可比性,对神经介入医师具有重要的指导意义。     

血管成形术和支架辅助血管成形术治疗颅内动脉粥样硬化的报告标准（上）

背景和目的颅内动脉粥样硬化可造成众多患者发生缺血性卒中。过去10年间血管内治疗技术已经取得突破性进展,能够开展颅内动脉粥样硬化性狭窄的血管内治疗。采用血管成形术和支架辅助阻管成形术治疗颅内动脉粥样硬化性狭窄的患者例数不断增加。但是鉴于目前血管成形术和支架辅助血管成形术治疗狭窄性和闭塞性颅内动脉粥样硬化仍缺乏普遍认可的临床和放射学评估以及皿管内治疗技术及预后的规范,此文就是提供该方面报告标准、术语和书面定义的共识性建议。报告摘要报告标准是在技术评价委员会、神经介入外科学会、介入放射学会、美国神经外科医师协会和神经外科医师代表大会的脑血管外科分会、美国神经科学会的卒中和介入神经病学分会的联合写作组共同起草完成。对1997年1月-2007年12月间,美国国立图书馆医学文献数据库（PubMed）进行计算机检索,旨在确定已发表的狭窄性颅内动脉粥样硬化的神经介入治疗中,能用作质量评价基准的资料。我们尽可能地确定影响神经介入治疗成功及并发症可能性的危险调节变量。对狭窄性和闭塞性颅内动脉粥样硬化进行麻管内治疗的临床试验设计中,不同临床和技术问题可能影响血管内治疗的疗效,此文章为这些问题提供相关的理论基础。该指南中包括对血管内治疗试验报告标准的建议。虽然制定规范和标准主要是出于研究用途,但是这也将有助于临床实践,还适用于所有相关的出版物。结论总之,报告标准提出的建议将有助于构建有效的研究数据库,同时促进产生科学可靠的研究结果,使相似研究之间或内部能够进行可靠的比较。存某些情况下,为报告和出版的一致性,本文中的定义可能是写作组专家的共识性建议。这些建议将促使不同研究组的结果具有直接可比性。     

Receptor localization, native tissue binding and ex vivo occupancy for centrally penetrant P2X7 antagonists in the rat

BACKGROUND AND PURPOSE

The P2X7 receptor is implicated in inflammation and pain and is therefore a potential target for therapeutic intervention. Here, the development of a native tissue radioligand binding, localization and ex vivo occupancy assay for centrally penetrant P2X7 receptor antagonists is described.

EXPERIMENTAL APPROACH

Autoradiography studies using the P2X7 antagonist radioligand [³H]-A-804598 were carried out in rat brain and spinal cord. Subsequent in vitro binding and ex vivo occupancy assays were performed using rat cortex homogenate.

KEY RESULTS

P2X7 expression was shown to be widespread throughout the rat brain, and in the grey matter of the spinal cord. In binding assays in rat cortex homogenate, ∼60% specific binding was achieved at equilibrium. In kinetic binding assays, k_on and k_off values of 0.0021·min⁻¹·nM⁻¹ and 0.0070·min⁻¹ were determined, and the K_d derived from kinetic measurements was consistent with that derived from saturation analysis. Novel P2X7 antagonists inhibited the binding of [³H]-A-804598 to rat cortex P2X7 receptors with K_i values of <40 nM. In an ex vivo occupancy assay, a P2X7 antagonist dosed orally to rats caused a concentration-dependent inhibition of the specific binding of [³H]-A-804598 to rat cortex.

CONCLUSIONS AND IMPLICATIONS

The present study describes the development of an assay that allows localization of P2X7 receptors, the measurement of the binding affinity of P2X7 receptor antagonists in native tissue, and provides a means of determining central P2X7 receptor occupancy. These assays could form an important part of a P2X7 drug discovery programme.     

世界胃肠病学组织全球指南——发展中国家幽门螺杆菌感染

世界上有一半人口感染幽门螺杆菌（H．pylori）,其感染率因地理位置、种族、年龄和社会经济状况不同而存在很大差异．在发展中国家较高．发达国家较低。但总体而言,近年世界许多地区的H．pylori感染率均呈下降趋势。