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.     

妊娠对大鼠吸入性全麻药血/气分配系数和组织/气分配系数的影响

目的 观察妊娠对大鼠吸人性全麻药血，气分配系数及组织，气分配系数的影响。方法 健康成年（3月龄）雌性妊娠（妊娠18—22d）和非妊娠SD大鼠各10只，分别为妊娠组和非妊娠组。腹腔注射戊巴比妥钠40mg／kg麻醉，经腹主动脉抽血用于测血，气分配系数，放血处死后，分别取心、肝、肾及脑组织并制成匀浆，采用注射器顶空二次平衡法经气相色谱仪测定七氟醚、异氟醚和氟烷的血，气分配系数及组织，气分配系数。结果与非妊娠组相比，妊娠组氟烷的血，气分配系数和脑，气分配系数降低（P〈0．05），七氟醚、异氟醚的血，气分配系数、肝，气分配系数、肾，气分配系数、心，气分配系数差异无统计学意义（P〉0．05）。结论 妊娠降低大鼠氟烷的血，气配系数和脑，气分配系数，但不影响七氟醚和异氟醚的血，气分配系数和组织，气分配系数。     

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。     

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。     

兔内听动脉阻断与听觉改变的关系

目的 探讨实验性内听动脉阻断与术后听力改变的关系及术中听觉监控的方法。方法 实验兔乙状窦后进路暴露小脑桥脑角，下压小脑暴露内听道及第Ⅷ神经复合体，分辨出内听动脉，予阻断不同时间，分别行蜗神经直接复合动作电位(DCAP)和畸变产物耳声发射记录(DPOAE)。结果对照组DCAPN1波潜伏期值无明显改变。内耳血供阻断10s和30s组在压迫开始后3min，DCAPN1波潜伏期值均恢复为初始值。内耳血供阻断1min组在压迫开始后3h，DCAPN1波潜伏期值未恢复为初始值假手术组DPOAE幅值无明显改变，内耳血供阻断10s、30s对DPOAE幅值无影响，内耳血供阻断1min使得DPOAE幅值下降结论兔内耳血供阻断1min可能造成兔听觉不可逆损伤。DCAP、DPOAE能有效、持续地监控内耳血供阻断，是耳神经外科手术中实用的听觉监测手段。     

市售三厂家18种复方氨基酸注射液的质量评价

目的对市售3厂家(A、B和E)共9批18种复方氨基酸注射液进行质量比较。方法参考国内外同类产品质量标准,从澄明度、透光率、性状、pH值、不溶性微粒、抗氧剂量、细菌内毒素和含量等方面进行比较。结果外观均为无色澄明液体,430nm波长处透光率均大于99%,pH在5.42～6.61间;A、B、E3厂不溶性微粒≥10、≥25μm的粒子数分别为1.41、0.32,0.83、0.21和1.55、0.56个/ml;抗氧剂的量分别为<33、近330和>500mg/L;细菌内毒素检查与含量测定符合中国药典及国家标准要求。结论不同厂家的产品质量确实存在一定的差异。     

备劳特联合爱喘乐雾化吸入治疗儿童哮喘急性发作的疗效观察

目的 :观察氧雾化吸入备劳特和爱喘乐治疗儿童哮喘急性发作的疗效。方法 :选择 15 8例哮喘急性发作患儿作为研究对象 ,分为观察组和对照组。观察组采用氧驱动雾化吸入备劳特和爱喘乐 ;对照组静脉滴注氨茶碱和地塞米松。结果 :观察组显效率 87.3% (96 /110 ) ,总有效率 99.1% (10 9/110 ) ,临床治愈率 94 .5 % (10 4 /110 ) ;对照组显效率 2 2 .9% (11/48) ,总有效率 6 0 .4 % (2 9/48) ,临床治愈率 5 4 .2 % (2 6 /48)。观察组显效率、总有效率及临床治愈率皆显著高于对照组 ,差异有高度统计意义 (P <0 .0 1)。观察组治疗后心率较治疗前明显下降 ,差异有统计意义(P <0 .0 5 )。结论 :采用氧驱动雾化吸入备劳特和爱喘乐能快速、有效地控制哮喘发作。