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.     

桃红四物汤联合银杏酮酯滴丸治疗老年出血性玻璃体混浊的临床疗效研究

目的:探究桃红四物汤联合银杏酮酯滴丸治疗老年出血性玻璃体混浊的临床疗效。方法:收集2016年12月-2018年12月我院收治的老年出血性玻璃体混浊患者67例,共67眼,根据随机对照表分为对照组和试验组,其中试验组34例,对照组33例,对照组予以银杏酮酯滴丸;试验组在对照组的基础上联用桃红四物汤。两组均服用30 d。治疗结束后对比分析两组患者临床疗效、出血吸收时间、血液流变学及视网膜中央动脉血流动力学。结果:治疗后两组患者高切全血粘度、低切全血粘度、纤维蛋白原、阻力指数(Resistance Index,RI)低于治疗前,收缩期峰值速度(Peak Systolic Velocity,PSV)、舒张末期血流速度(End Diastolic Velocity,EDV)高于治疗前,差异具有统计学意义(P<0.05);治疗后试验组临床总有效率、PSV、EDV高于对照组,出血吸收时间、高切全血粘度、低切全血粘度、纤维蛋白原、RI低于对照组,差异具有统计学意义(P<0.05)。结论:桃红四物汤联合银杏酮酯滴丸治疗老年出血性玻璃体混浊临床疗效显著,适宜临床应用推广。     

基于“证治代谢组学”假说探讨中药（单体/复方）药效物质基础的研究思路与实践＊

中药(单体/复方)药效物质基础研究是中医药现代研究的关键问题之一。然而,目前运用的生化和分子生物学方法很难诠释其多靶点、整体性和动态性的整合调节作用。课题组提出的"证治代谢组学"假说理论指出,不同的证候存在"证相关代谢谱群"和"证相关生物标志物",这可能是中药药效物质基础所在,辨证论治后偏离的代谢网络功能呈现回归趋势。基于"证治代谢组学"假说开展中药(单体/复方)药效物质基础研究,这将为阐释中药(单体/复方)防病治病和养生保健的科学内涵及其对疾病个体的整合调节作用提供新的思路。本文以冠心病为研究载体、气阴虚血瘀证为切入点、活血保心丸为干预措施,就该研究思路的内涵与总体模式、提出的背景与依据、实践的方式与可行性、创新与特色及其研究意义等进行了简要介绍。     

复方碘酊消毒液中和剂试验研究

复方碘酊消毒液是含有20 g/L碘和1 g/L三氯羟基二苯醚的酒精溶液,为选择出合适的中和剂,采用化学中和法的悬液定量试验和滤膜冲洗及中和剂加滤膜冲洗法进行了试验研究。结果,硫代硫酸钠、硫代乙醇酸钠、吐温80、卵磷脂及其复方中和剂经悬液定量试验法和滤膜冲洗法,均不能中和复方碘酊消毒液对试验菌的残留作用。采用中和剂加滤膜冲洗法证明,用含5000 mg/L硫代硫酸钠+5000 mg/L吐温80+2000 mg/L硫代乙醇酸钠的磷酸盐缓冲液作为中和剂,均可有效去除复方碘酊消毒液对试验菌的残留作用;各中和剂及其中和产物对试验菌及培养基无不良影响。结论,选择复方碘酊消毒液的中和剂,不适宜用悬液定量试验法;宜采用滤膜过滤冲洗法。     

The effect of MS-818, a pyrimidine compound,on the regeneration of peripheral nerve fibers of mice after a crush injury

One of the pyrimidine compounds, 2-piperadino-6-methyl-5-oxo-5,6-dihydro(7H)pyrrolo[3,4-d]pyrimidine (MS-818), has neurotropic effects in vitro. Therefore, we studied the effect of MS-818 on the regeneration of the peroneal nerve in C57BL/6J mice after a crush injury. Two test groups, which received a daily intraperitoneal injection of 5 mg/kg or 10 mg/kg MS-818, respectively, were compared with controls, which received daily intraperitoneal injections of physiological saline, over a 14-day period. The maximum foot-width ratio (crushed side/uncrushed side) was obtained on days 1, 8 and 14 after the crush injury, and the various morphometric parameters were evaluated at both 5 and 10 mm distal to the proximal portion of the crush site. The significant effects of MS-818 included a larger maximum foot width (P<0.04) and a greater number of unmyelinated axons per nerve at both levels (P<0.003) in both test groups than in controls. MS-818 had no significant effects on body weight, the increase of total transverse fascicular area after the crush injury, the total number of myelinated fibers with their size distributions, or the number of nuclei of Schwann cells and macrophages. Therefore, we conclude that MS-818 promotes axonal sprouting and elongation after a crush injury in mice.     

复方华蟾胶囊抗小鼠肿中瘤作用的实验研究

目的了解复方华蟾胶囊抗小鼠移植性肿瘤的作用.方法以小鼠肝癌22(H22)、小鼠肉瘤180(S180)为瘤株,应用动物移植性肿瘤的体内试验法对药物进行抗癌药效学试验.结果复方华蟾胶囊灌胃4,2 g/kg@d,连续14 d,对小鼠移植性肝癌实体型生长有明显的抑制作用,抑瘤率分别为38.09%,30.95%.对小鼠移植性S180实体型生长有明显的抑制作用,抑瘤率分别为34.7%,30.08%.复方华蟾胶囊对荷瘤小鼠的胸腺和脾脏重量无影响.结论复方华蟾胶囊在试验条件下有一定抗肿瘤作用.     

老年护理院医院感染病原菌及其耐药特征分析

目的探讨目前老年护理医院院内感染病原菌及其耐药特征。方法对2000年4月-2004年3月徐汇区两家老年护理院出院病人的病史进行统计分析。结果两家老年护理院共计发生医院感染939例次，医院感染率12．86％，检出病原菌284株，阳性率30．28％；病原菌以革兰阴性菌为主，占44．65％，其次为真菌、革兰阳性菌，分别为29．12％、25．92％，位于前3位的病原菌分别为其他真菌（14．36％）、白色念珠菌（12．23％）、铜绿假单胞菌（8．69％）；除嗜麦芽寡养单胞菌外，革兰阴性菌以亚胺培南最敏感，敏感率87％，对氨苄西林、阿莫西林的耐药率〉51％，对头孢哌酮、哌拉西林的耐药率〉33％；MRSA和MRSE的检出率高达86．76％和76．32％；混合感染率34．51％。结论老年护理院医院感染率高．真菌所占的比例高；细菌对抗菌药物的耐药性相当严重。     

中药内外并用抗尖锐湿疣复发的临床研究

目的：观察中药消疣丸/消疣擦剂内服外用防止尖锐湿疣复发的作用.方法：应用免疫学方法，检测患者治疗前后外周血T淋巴细胞亚群CD3、CD4、CD8的百分率和CD4/CD8的比值.结果：局部消除疣体后中药消疣丸/消疣擦剂内服外用对防止尖锐湿疣复发有显著疗效，痊愈率为99.66%，复发率为3.33%，与对照组相比有显著差异（P〈0.05）.结论：中药内服外用抗尖锐湿疣复发效果好。     

大型尿基复合肥养分偏差的原因分析及措施

介绍大型尿基复合肥装置在生产中引起产品养分偏差的原因及采取的操作措施。