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用于评估西奈芬净抗隐孢子虫活性的免疫抑制大鼠模型。

An immunosuppressed rat model for evaluation of anti-Cryptosporidium activity of sinefungin.

作者信息

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

机构信息

Department of Parasitology, Hôpital Charles Nicolle, Rouen, France.

出版信息

Folia Parasitol (Praha). 1994;41(1):13-6.

PMID:8050749
Abstract

Cryptosporidium parvum causes life-threatening diarrhoea in immunocompromised, especially AIDS patients and the efficiency of proposed anti-cryptosporidial therapies is limited or doubtful. An immunosuppressed adult rat model of C. parvum infection was developed for screening molecules candidate for curative and preventive activity in human cryptosporidiosis. Among 31 drugs tested, lasalocid (2-10 mg/kg/24 h), and sinefungin (2-10 mg/kg/24 h), exhibited some activity against C. parvum infection. Oral sinefungin therapy resulted in a dose related suppression of oocysts shedding, which correlated with oocyst disappearance from ileum sections and was also efficient in preventing infection. Relapses were observed after discontinuation of curative sinefungin therapy, which suggests that the biliary tract, a major location and parasite reservoir which sustains persisting infection, was not cleared of parasites by the drug. Improved therapeutic procedures with sinefungin (or analogues) will result from current pharmacological studies.

摘要

微小隐孢子虫可在免疫功能低下者,尤其是艾滋病患者中引发危及生命的腹泻,而目前所提出的抗隐孢子虫疗法的疗效有限或存在疑问。为筛选对人类隐孢子虫病具有治疗和预防活性的候选分子,构建了微小隐孢子虫感染的免疫抑制成年大鼠模型。在所测试的31种药物中,拉沙洛西(2 - 10毫克/千克/24小时)和西奈芬净(2 - 10毫克/千克/24小时)对微小隐孢子虫感染表现出一定活性。口服西奈芬净治疗导致卵囊排出呈剂量相关抑制,这与回肠切片中卵囊消失相关,并且在预防感染方面也有效。在停止西奈芬净治疗后观察到复发情况,这表明作为持续感染的主要部位和寄生虫储存库的胆道未被该药物清除寄生虫。当前的药理学研究将带来使用西奈芬净(或类似物)的改进治疗程序。

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