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1.
《Drug discovery today》2022,27(6):1733-1742
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. 相似文献
2.
Xin Mei Jiang Akio Ohnishi Tatsunori Yamamoto Yoshiyuki Murai Akira Awaya Masato Ikeda 《Acta neuropathologica》1995,90(2):130-134
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. 相似文献
3.
复方华蟾胶囊抗小鼠肿中瘤作用的实验研究 总被引:2,自引:0,他引:2
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. 相似文献
4.
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。 相似文献
5.
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。 相似文献
6.
黄传贵 《世界今日医学杂志》2007,8(3):131-132
目的 总结复方金荞麦颗粒治疗肺癌的疗效。方法 对1000例各种类型的肺癌患者采用复方金荞麦颗粒5g,3次·d^-1 口服,同时辅以中药汤剂治疗,3mo为1疗程,病情稳定后逐渐减量维持。结果本组1000例患者经3mo~15a以上治疗,基本治愈181例(18.1%),显效518例(51.8%),有效204例(20.4%),无效97例(9.7%),总有效率为90.3%。结论 复方金荞麦颗粒为抗肿瘤的纯中药制剂,具有明显抑制肿瘤细胞生长、增强免疫功能、提高患者生存质量等功效,尤其是对失去手术治疗机会、不能接受化疗和放疗的肺癌患者具有较好疗效。 相似文献
7.
采用细胞内微电极记录技术,同步观察了3,6-[二甲氨基]-二苯并碘因甲酸盐(IHC-64)对豚鼠心乳头肌细胞动作电位和收缩力的作用。50μmol/L IHC-64抑制心肌收缩力,而不影响快反应动作电位。增加IHC-64浓度,动作电位0相最大峰值(APA)、除极速率(dp/dt_(max))和复极50%和90%时程(APD_(50)、APD_(90))被明显抑制。IHC-64抑制慢反应动作电位,提高细胞外钙浓度可拮抗这种抑制。结果提示,IHC-64主要抑制慢Ca~(2+)内流,同时也部分抑制快Na~+内流,它可能是一种新型B类钙通道阻滞剂。 相似文献
8.
复方麝香注射液联合脑血肿引流术治疗中老年高血压脑出血疗效观察及费用对比 总被引:6,自引:1,他引:5
目的:探讨复方麝香注射液联合微创手术治疗中老年高血压脑出血的临床疗效.方法:将78例接受微创治疗的患者随机分组,两组均采用内科综合治疗.手术对照组在综合治疗基础上加用微创手术进行脑血肿引流;中西医结合组在微创手术治疗后加用复方麝香注射液(10~20 ml/d)静脉滴注1周.结果:中西医结合组显效率(66.67%)、有效率(82.05%)均明显高于手术对照组(46.15%和69.23%,P均<0.05),存活患者日常生活能力也明显优于手术对照组(P<0.05),意识恢复时间明显短于手术对照组(P<0.05),并发症的发生率(15.38%)明显低于手术对照组(38.46%,P<0.01),病死率(5.13%)明显低于手术对照组(10.26%,P<0.01),平均住院天数[(18.29±4.93)d]明显少于手术对照组[(26.23±5.82)d,P<0.05],平均住院费用[(5 916.23±826.39)元]明显少于手术对照组[(8 168.35±1 021.21)元,P<0.05].结论:脑血肿引流术后加用复方麝香注射液治疗中老年高血压脑出血,可降低病死率,减少并发症,降低病残程度,提高生存患者的生活质量,缩短住院时间,降低治疗费用. 相似文献
9.
Summary— The regulation and role of the intracellular Ca2+ pools were studied in rat peritoneal mast cells. Cytosolic free calcium concentration ([Ca2+ ]i) was monitored in fura-2 loaded mast cells. In the presence of Ca2+ and K+, compound 48/80 induced a biphasic increase in [Ca2+ ]i composed of a fast transient phase and an apparent sustained phase. The sustained phase was partially inhibited by the addition of Mn2+ . DTPA, a cell-impermeant chelator of Mn2+ , reversed this inhibition, suggesting that a quenching of fura-2 fluorescence occurs in the extracellular medium. In the absence of extracellular Ca2+ , the transient phase, but not the sustained one, could be preserved, provided that mast cells were depolarized. The transient phase was completely abolished by thapsigargin, a microsomal Ca2+ -ATPase inhibitor. Maximum histamine release induced by either compound 48/80 or antigen was obtained in the absence of added Ca2+ only when mast cells were depolarized. These histamine releases were inhibited by low doses (< 30 nM) of thapsigargin. Thapsigargin at higher doses induced histamine release which was unaffected by changing the plasma membrane potential, but was completely dependent on extracellular Ca2+ , showing that a Ca2+ influx is required for thapsigargin-induced exocytosis. Together, these results suggest that the mobilization of Ca2+ from thapsigargin sensitive-intracellular pools induced by compound 48/80 or antigen is sufficient to trigger histamine release. The modulation of these pools by the plasma membrane potential suggest their localization is close to the plasma membrane. 相似文献
10.
特安瑞林(Treplorelin)的致突变与致畸作用的研究陆其明(上海医科大学公共卫生学院,200032)特安瑞林(Treplorelin,D-Trp-6-LHRH)是一种用于治疗子宫肌瘤的新药,其药理作用能促进性腺激素释放,使子宫内膜脱落和子宫肌瘤... 相似文献