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对有前景的抗丝虫药体外抗盘尾丝虫成虫可行性的初步评估。

A preliminary assessment of the feasibility of evaluating promising antifilarials in vitro against adult Onchocerca volvulus.

作者信息

Comley J C, Szopa T M, Strote G, Buttner M, Darge K, Buttner D W

机构信息

Molecular Sciences Department, Wellcome Research Laboratories, Beckenham, Kent, UK.

出版信息

Parasitology. 1989 Dec;99 Pt 3:417-25. doi: 10.1017/s003118200005914x.

Abstract

The suitability of motility indices and tetrazolium-based colorimetric assays for the determination of the viability of adult Onchocerca volvulus after in vitro exposure to potential macrofilaricides has been examined. Experimentation showed that both techniques could be applied to adult O. volvulus, although the variability between individual worms necessitated the use of large experimental groups. The potential of using cut anterior tips of female O. volvulus for screening was also investigated. These were shown to give reasonably consistent motility indices, and drug effects were discernible even after 72 h in vitro culture. Application of these viability criteria to studies on the short-term in vitro survival of intact male and female O. volvulus incubated in Eagles MEM plus serum, under 5% CO2 in air, showed this medium to be suboptimal with a greater than 50% loss of worm viability within 144 h of nodulectomy. Males isolated by the collagenase technique were shown to be significantly less viable than dissected males, by both motility indices and tetrazolium reduction. The results highlight the need to use either dissected males, or in the case of females, the need to minimize exposure to collagenase solution. A possible mechanism for selecting a more uniformly viable female worm population is discussed. Examination of the in vitro effects of CGP 20376 using these viability criteria/assay systems showed some delayed suppression of worm motility, but after 120 h in vitro CGP 20376 was not macrofilaricidal against male or female O. volvulus. Male worms were also implanted subcutaneously into gerbils.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

研究了运动指数和基于四氮唑的比色法在体外暴露于潜在的杀成虫药后测定成年旋盘尾丝虫活力的适用性。实验表明,这两种技术均可应用于成年旋盘尾丝虫,尽管个体虫体之间的变异性使得需要使用大型实验组。还研究了使用雌性旋盘尾丝虫切断的前端进行筛选的潜力。结果表明,这些前端能给出相当一致的运动指数,即使在体外培养72小时后,药物作用也清晰可辨。将这些活力标准应用于在含有血清的伊格尔氏MEM培养基中、于5%二氧化碳空气环境下培养的完整雄性和雌性旋盘尾丝虫的短期体外存活研究中,结果显示该培养基不理想,在结节切除后144小时内,虫体活力损失超过50%。通过胶原酶技术分离的雄性虫体,无论是运动指数还是四氮唑还原试验,其活力均显著低于解剖分离的雄性虫体。结果强调,对于雄性虫体需使用解剖分离的虫体,对于雌性虫体,则需尽量减少其与胶原酶溶液的接触。文中讨论了选择更具一致活力的雌性虫群体的可能机制。使用这些活力标准/检测系统研究CGP 20376的体外作用,结果显示对虫体运动有一定延迟抑制作用,但在体外培养120小时后,CGP 20376对雄性或雌性旋盘尾丝虫均无杀成虫作用。雄性虫体也被皮下植入沙鼠体内。(摘要截选至250字)

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