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原唇鼠口腔内的德氏双瓣线虫。II. 抗丝虫化疗药理学研究模型的评估(作者译)

[Dipetalonema dessetae in Proechimys oris. II. Evaluation of the model for pharmacologic investigations of antifilarial chemotherapy (author's transl)].

作者信息

Gayral P, Dreyfuss G, Gantier J C

出版信息

J Pharmacol. 1982 Jan-Mar;13(1):49-63.

PMID:7200173
Abstract

Dipetalonema dessetae in Proechimys oris is a new model of rodent feafilariasis with several interesting features with respect to its utilisation in antifilarial pharmacology. 1. In the first part of these studies, it has been shown that the final host of the filaria, a rodent, was easy to breed. A prolific mosquito Aedes aegypti was an effective vector, and with the selected mode of infection i.e. 200 infesting larvae subcutaneously injected, 80% of the rodents were infected. 2. From 90 to 150 days p.i., the microfilaria count increased and reach a plateau which was maintained during 60 days. This plateau has enabled the evaluation of microfilaricidal activity. A drug exhibited a significative (0,10) microfilaricidal activity in two animals if the microfilaremia were reduced to 87% and 83,6% of pretreatment values, two or six weeks after treatment. 3. Identically, a compound would present a significative (0,12) macrofilaricidal effect if not a single male and not more than 1,6 female filaria were found at the autopsy of both animals six weeks after treatment. Activity on immature worms (3rd and 4th instar larvae, young adults) was qualitatively evaluated by the presence or absence of filaria at the autopsy of rodents which have been treated at various dates depending of the stages. 4. The sensitivity of this model was evaluated with several known antifilarial drugs, some of them unused by human patients. Diethylcarbamazine, levamisole, suramin, mebendazole and flubendazole killed adults, microfilariae and infesting larvae. Mel W was mainly macrofilaricidal and trichlorfon active on mf. Among all laboratory filariae, D. dessetae in P. oris is one of the most sensitive rodent models and, as such, would serve for the primary screening of new chemical compounds and for the pharmacological studies of antifilarial drugs.

摘要

奥氏原鼠体内的德氏双瓣线虫是一种新的啮齿动物丝虫病模型,在抗丝虫药理学应用方面具有几个有趣的特征。1. 在这些研究的第一部分中,已表明丝虫的终宿主——一种啮齿动物易于繁殖。多产的埃及伊蚊是有效的传播媒介,采用选定的感染方式,即皮下注射200条感染性幼虫,80%的啮齿动物被感染。2. 感染后90至150天,微丝蚴数量增加并达到一个平台期,该平台期持续60天。这个平台期使得能够评估微丝蚴杀灭活性。如果在治疗后两周或六周,微丝蚴血症降至治疗前值的87%和83.6%,则一种药物在两只动物中表现出显著(0.10)的微丝蚴杀灭活性。3. 同样,如果在治疗六周后对两只动物进行尸检时未发现单条雄虫且雌虫不超过1.6条,则一种化合物将呈现显著(0.12)的成虫杀灭效果。根据不同阶段在不同日期对啮齿动物进行治疗,通过尸检时是否存在丝虫来定性评估对未成熟虫体(第3和4期幼虫、年轻成虫)的活性。4. 用几种已知的抗丝虫药物评估了该模型的敏感性,其中一些药物未被人类患者使用。乙胺嗪、左旋咪唑、苏拉明、甲苯达唑和氟苯达唑可杀死成虫、微丝蚴和感染性幼虫。Mel W主要具有成虫杀灭作用,敌百虫对微丝蚴有活性。在所有实验室丝虫中,奥氏原鼠体内的德氏双瓣线虫是最敏感的啮齿动物模型之一,因此可用于新化合物的初步筛选和抗丝虫药物的药理学研究。

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引用本文的文献

1
Experimental filariasis of Dipetalonema dessetae in Proechimys oris: 3. Effects of parasitism on the pharmacokinetics of diethylcarbamazine.德氏双瓣线虫在奥利鼠兔体内的实验性丝虫病:3. 寄生虫感染对乙胺嗪药代动力学的影响。
Eur J Drug Metab Pharmacokinet. 1983 Oct-Dec;8(4):313-20. doi: 10.1007/BF03188763.
2
[Experimental filariasis in Proechimys oris by Dipetalonema dessetae. 5. Effect of parasitism on metabolism of diethylcarbamazine].[德斯氏双瓣线虫致奥氏原鼠实验性丝虫病。5. 寄生虫感染对乙胺嗪代谢的影响]
Eur J Drug Metab Pharmacokinet. 1986 Jul-Sep;11(3):211-23. doi: 10.1007/BF03189849.