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鸡疟原虫:具有根治特性药物的禽类筛选模型

Plasmodium gallinaceum: avian screen for drugs with radical curative properties.

作者信息

Gwadz R W, Koontz L C, Miller L H, Davidson D E

出版信息

Exp Parasitol. 1983 Apr;55(2):188-96. doi: 10.1016/0014-4894(83)90013-9.

Abstract

Existing primary screens for radical curative antimalarial drugs fail to adequately detect many compounds which affect the latent, exoerythrocytic hypnozoite, the stage of the parasite responsible for relapse. At the same time, these screens falsely identify a wide range of compounds with no radical curative activity. The avian malaria, Plasmodium gallinaceum, and Aedes aegypti mosquitos were used in a screen which measures the effects of candidate compounds on gametocytes and their development within the mosquito. Sporontocidal and gametocytocidal effects could be differentiated by this screen. In a blind study, those compounds shown to be exclusively gametocytocidal were those same drugs which had previously been shown to have radical curative effects against true relapsing malarias. The chicken malaria gametocyte screen was more sensitive than the rodent screens in detecting useful compounds, with a minimum of false positive identifications.

摘要

现有的用于根治性抗疟药物的初步筛选方法未能充分检测出许多影响潜伏性、红细胞外期休眠子(导致疟疾复发的寄生虫阶段)的化合物。与此同时,这些筛选方法错误地鉴定出大量没有根治活性的化合物。在一项筛选中使用了鸡疟原虫(Plasmodium gallinaceum)和埃及伊蚊,该筛选可测量候选化合物对配子体及其在蚊子体内发育的影响。通过此筛选可以区分杀孢子体和杀配子体的作用。在一项盲法研究中,那些仅表现出杀配子体作用的化合物正是之前被证明对真正复发性疟疾具有根治作用的药物。鸡疟配子体筛选在检测有用化合物方面比啮齿动物筛选更敏感,假阳性鉴定最少。

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