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一种利用不同形态的旋盘尾丝虫进行抗丝虫药物体外测定的新技术。

A new technique of in vitro assay of antifilarials using different life-forms of Acanthocheilonema viteae.

作者信息

Singh D P, Misra S, Chatterjee R K

机构信息

Division of Parasitology, Central Drug Research Institute, Lucknow, India.

出版信息

Jpn J Exp Med. 1990 Dec;60(6):303-9.

PMID:2096223
Abstract

An approach has been made to develop an in vitro screening system to evaluate antifilarial efficacy of compounds and an effort has been made to establish correlation between in vivo and in vitro screening technique. The in vitro experiments were conducted simultaneously using three life-forms (adult, microfilaria and infective larva) of Acanthocheilonema viteae using five antifilarial agents representing four chemical groups. All the selected antifilarials were known to be active against one or more life-stages of human lymphatic or animal filariids. Diethylcarbamazine and Centperazine showed 100% microfilaricidal and infective larvicidal actions at concentrations of 0.5 and 0.25 mg/ml and 0.5 and 0.0313 mg/ml respectively with no effect on adult worms even at 1 mg/ml. Levamisole was effective against all the three life-stages killing 100% adult worms at 1 mg/ml, infective larvae at 0.0625 mg/ml and microfilariae at 0.0125 mg/ml, while mebendazole exhibited activity only against adult worms (100% at 0.5 mg/ml). Ivermectin killed adult females and microfilariae at 0.063 and 0.5 mg/ml respectively but did not affect infective larvae even up to 1 mg/ml concentration. The study indicated that in vitro screening system can be used for primary screening of potential antifilarial agents provided three life-forms of A. viteae are used simultaneously to avoid false negative results. It would however be more appropriate if a few compounds of a particular chemical class are initially assessed both in vivo and in vitro for validity of subsequent test results in vitro.

摘要

已着手开发一种体外筛选系统,以评估化合物的抗丝虫功效,并努力建立体内和体外筛选技术之间的相关性。使用代表四个化学组的五种抗丝虫药物,同时对棘唇旋尾线虫的三种生命形式(成虫、微丝蚴和感染性幼虫)进行体外实验。所有选定的抗丝虫药物均已知对人类淋巴丝虫或动物丝虫的一个或多个生命阶段具有活性。乙胺嗪和哌嗪分别在浓度为0.5和0.25mg/ml以及0.5和0.0313mg/ml时显示出100%的杀微丝蚴和杀感染性幼虫作用,即使在1mg/ml时对成虫也无影响。左旋咪唑对所有三个生命阶段均有效,在1mg/ml时杀死100%的成虫,在0.0625mg/ml时杀死感染性幼虫,在0.0125mg/ml时杀死微丝蚴,而甲苯达唑仅对成虫有活性(在0.5mg/ml时为100%)。伊维菌素分别在0.063和0.5mg/ml时杀死成年雌虫和微丝蚴,但即使在浓度高达1mg/ml时也不影响感染性幼虫。该研究表明,如果同时使用棘唇旋尾线虫的三种生命形式以避免假阴性结果,体外筛选系统可用于潜在抗丝虫药物的初步筛选。然而,如果最初对特定化学类别的一些化合物进行体内和体外评估,以验证后续体外测试结果的有效性,则会更合适。

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