Redox active or thiol reactive? Optimization of rapid screens to identify less evident nuisance compounds

Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action.     

8种寄生虫病例分析

本文报道并分析8例寄生虫病例,其中包括脑裂头蚴病、眼部裂头蚴病、肺吸虫幼虫移行症、肺吸虫病、钩虫病、肝吸虫病、包虫病和广州管圆线虫病各1例。8例寄生虫病均有不同程度的误诊,其中6例在寄生虫抗体筛查检测阳性后得以确诊。因此,寄生虫病应引起临床医生的重视,抗体筛查有助于发现寄生虫病例。     

Preclinical Drug Metabolism in the Age of High-Throughput Screening: An Industrial Perspective

With the advent of genomics, combinatorial paradigms and high-throughput screen (HTS)-based pharmacological testing, the number of compounds flowing through the discovery pipeline is likely to escalate. At the same time, with increased knowledge of the human drug-metabolizing enzymes and the availability of in vitro absorption-metabolism (AM) models, Preclinical Drug Metabolism is poised to meet the challenges of HTS. In order to be successful, however, a rational HTS strategy (vs. serendipitous HTS) has to be employed. Such a strategy is based on automation, validation and integration of in vitroAM models and database management (AVID). A generalized strategy for rational (AVID-based) HTS in Preclinical Drug Metabolism is described briefly.     

天然放射性气溶胶的粒径分布及其测量方法

天然放射性气溶胶粒径分布的变化会引起氡及其子体所致肺剂量的较大涨落。由于我国对其报道甚少，在肺剂量估算中均引用ＵＮＳＣＥＡＲ的推荐值。为验证这种引用的合理性和建立气溶胶粒径分布的测量方法，开展本项研究。方法采用金属丝网筛（１６５目）扩散法测量天然空气经不同数目网筛扩散前后的放射性浓度比（衰减比）来绘制衰减曲线，然后用池边模式计算出粒径分布曲线。衰减比、粒径分布的计算和曲线的绘制均采用计算机。结果室内外天然放射性气溶胶粒径呈几何正态分布，分布的峰值的平均值分别为（０．２０±０．０９）μｍ和（０．２７±０．１１）μｍ。粒径分布和氡浓度、气压、气温、湿度等未发现相关关系。结论本研究结果与ＵＮＳＣＥＡＲ报告书（１９８８）的推荐值相比，室内值相同，室外值略高，与Ｊａｃｏｂｉ的研究相近。由此可得出结论，福州地区引用ＵＮＳＣＥＡＲ报告书的推荐值来估算氡及其子体所致肺剂量是合适的。此结论能否推广到其他地区，还需作进一步的研究。     

ABS-2000全自动血库系统临床应用评价研究

目的:通过相应的测定对自动化血库系统适用性和安全性进行全面评价,并对输血相容性检测方法与常规手工方法进行全面对比.方法:使用人工设计的各种样本对仪器进行特异性、灵敏度及抗干扰试验的对比评估,以及对临床常规9108例标本进行ABO正反定型,Rh(D)测定及抗体筛检测定,并对相应结果进行对比分析.结果:对人工设置的各种测定标本,在特异性、灵敏度和抗干扰试验中,测定结果均能达到设计要求,并优于手工Polybrene方法.ABO血型测定9108份,除正反定型不符.228份,报告NTD给予提示外,其它测定血型全部与报告血型相符;Rh(D)所测结果为4份NTD,9104份结果全部相符.抗体筛检测定9108份,抗筛阳性383份,使用同一种抗筛细胞进行手Polybrene方法抗筛测定阳性仅为228份,统计学有显著性意义(P＜0.005).结论:ABS2000应用的固项检测技术具有较高的敏感度,能检测出较弱的IgG类的不规则及自身抗体,以上检测结果及统计情况与国外相关报道情况相符,此仪器在临床检测中使用可以达到保证安全检测的目的.     

Don’t Let an Opportunity Go by: Validation of the EIGHT Gambling Screen

The EIGHT Screen is a brief problem gambling screen originally designed for use by family doctors. Its wider use indicated the need for further validation. A triangulated approach used a range of measures in different settings in both the current study and findings from a number of earlier projects, and reviewed current use. The EIGHT Screen had acceptable correlations with the SOGS (r = 74–90%) and with the NODS-12 months Screen (r = 62.4%). Measurements remained relatively constant amongst a range of cultures, settings, age and gender, while few false positives were produced by the screen. The EIGHT Screen appears to be a valid tool for untrained users to identify Level 2 and 3 problem gambling in a wide range of cultures and settings.     

Genetic screen for mutations affecting development and function of the enteric nervous system.

An intact enteric nervous system is required for normal gastrointestinal tract function. Several human conditions result from decreased innervation by enteric neurons; however, the genetic basis of enteric nervous system development and function is incompletely understood. In an effort to increase our understanding of the mechanisms underlying enteric nervous system development, we screened mutagenized zebrafish for changes in the number or distribution of enteric neurons. We also established a motility assay and rescreened mutants to learn whether enteric neuron number is correlated with gastrointestinal motility in zebrafish. We describe mutations isolated in our screen that affect enteric neurons specifically, as well as mutations that affect other neural crest derivatives or have pleiotropic effects. We show a correlation between the severity of enteric neuron loss and gastrointestinal motility defects. This screen provides biological tools that serve as the basis for future mechanistic studies.     

简易精神状态检查适用人群及影响因素

目的：根据简易精神状态检查（MMSE）在大样本人群中的测试结果分析，探讨MMSE的适应人群及影响因素。方法：通过随机整群分层抽样，对4921名55岁或以上的西安市城市居民进行MMSE测查。分析MMSE得分在不同年龄，不同文化程度以及总体人群中的第10百分数、中位数、偏度、峰度以及对痴呆的阳性预测值。并用多元逐步回归法分析MMSE得分的影响因素。结果：MMSE得分在不同年龄、不同文化程度、总体人群中都呈现负偏态，尖峭峰型分布。在年龄较轻（70岁以下）、文化程度偏高（初中或以上）的人群中偏性分布最明显，痴呆的检出率较低；而在年龄偏大（70岁以上），文化程度偏低（小学及以下）的人群中接近正态分布，痴呆的检出率较高。文化程度、年龄、性别、受教育年限、听力下降、日常生活能力对MMSE得分有显著影响（P＜0．001）。结论：MMSE量表最适用于年龄偏大（70岁以上），文化程度偏低（小学或以下）的人群，对痴呆的筛选能力大；而对于年龄偏小，文化程度偏高的人群，MMSE的鉴别筛选力较低。实践中应根据具体研究目的选用适宜量表，并灵活掌握分界值，以达到最大效益。     

Allergic conversion of protective mucosal immunity against nasal bacteria in patients with chronic rhinosinusitis with nasal polyposis

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