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在免疫抑制大鼠模型中评估候选抗隐孢子虫药物

Assessment of candidate anticryptosporidial agents in an immunosuppressed rat model.

作者信息

Lemeteil D, Roussel F, Favennec L, Ballet J J, Brasseur P

机构信息

Department of Parasitology, Hôpital Charles-Nicolle, Centre Hospitalier Universitaire, Rouen, France.

出版信息

J Infect Dis. 1993 Mar;167(3):766-8. doi: 10.1093/infdis/167.3.766.

Abstract

Cryptosporidium parvum causes life-threatening diarrhea in immunocompromised patients, especially those with AIDS. The efficiency of currently proposed anticryptosporidial therapies is limited or doubtful. In this report, molecular candidates for curative or preventive activity were investigated in an immunocompromised rat model that mimics severe human cryptosporidiosis. No significant anticryptosporidial activity was observed when using sulfadoxine-pyrimethamine, quinacrine, trimethoprim-sulfamethoxazole, bleomycin, elliptinium, daunorubicin, pentamidine, alpha-difluoro-methylornithine, diclazuril or N-methylglucamine. Vitamin A appeared to reduce oocyst shedding. Active agents included sinefungin (2-10 mg/kg/24 h), lasalocid A (2-10 mg/kg/24 h), metronidazole (25-50 mg/kg/24 h), and sulfadimethoxine (10-100 mg/kg/24 h). Sinefungin (10 mg/kg/24 h) and lasalocid A (10 mg/kg/24 h) displayed the highest anticryptosporidial activity.

摘要

微小隐孢子虫可导致免疫功能低下患者,尤其是艾滋病患者出现危及生命的腹泻。目前所提出的抗隐孢子虫疗法的疗效有限或存疑。在本报告中,在一种模拟严重人类隐孢子虫病的免疫功能低下大鼠模型中研究了具有治疗或预防活性的分子候选物。使用磺胺多辛 - 乙胺嘧啶、奎纳克林、甲氧苄啶 - 磺胺甲恶唑、博来霉素、椭圆玫瑰树碱、柔红霉素、喷他脒、α - 二氟甲基鸟氨酸、地克珠利或N - 甲基葡糖胺时未观察到显著的抗隐孢子虫活性。维生素A似乎可减少卵囊排出。活性剂包括西奈芬净(2 - 10毫克/千克/24小时)、拉沙洛西A(2 - 10毫克/千克/24小时)、甲硝唑(25 - 50毫克/千克/24小时)和磺胺二甲氧嘧啶(10 - 100毫克/千克/24小时)。西奈芬净(10毫克/千克/24小时)和拉沙洛西A(10毫克/千克/24小时)表现出最高的抗隐孢子虫活性。

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