EVALUATION OF DRUGS FOR ANTICRYPTOSPORIDIAL ACTIVITY

隐孢子虫病是一种公认的肠道疾病，在艾滋病患者和 其他免疫功能低下的宿主，急需有效的治疗 需要的。长期目标是确定慢性阻塞性肺疾病的治疗方案 艾滋病患者的隐孢子虫病。这项建议的具体目标 研究是确定适当的剂量、治疗持续时间和 治疗时间表将使个别药物或药物 根除或控制隐孢子虫感染的组合 免疫抑制的大鼠。雌性SD大鼠(225-250克)将是 地塞米松(0.25 mg/kg/d)免疫抑制10天，感染 用标准剂量的牛源微小隐孢子虫卵囊，以及 然后用具有特定作用模式的药物治疗原生动物。 根据特定的目标，实验动物将被牺牲11到79只 卵囊接种后数天，确定感染程度 苏木精-伊红染色切片的组织学分析 小肠和大肠。测试中感染的严重程度 药物治疗组与免疫抑制组比较 非药物对照组和药物阳性对照组。除了……之外 评估单个药物的抗隐孢子虫活性 将评估组合的协同抗隐孢子虫活性。 在免疫抑制大鼠模型中。其主要目标是确定 具有抗隐孢子虫活性的药物及其条件的表征 因此这些药物可以有效地治疗隐孢子虫病和 消灭寄生虫。

Cryptosporidiosis is a well-recognized enteric disease in AIDS patients and other immunocompromised hosts, for which effective therapy is urgently needed. The long term goal is to identify treatment regimens for chronic cryptosporidiosis in AIDS patients. The specific aims of this proposed research are to determine the appropriate dose, treatment duration and therapeutic schedules that would enable individual drugs or drug combinations to either eradicate or control a cryptosporidial infection in immunosuppressed rats. Female Sprague-Dawley rats (225-250 gm) will be immunosuppressed with dexamethasone (0.25 mg/kg/day) for 10 days, infected with a standard dose of bovine-derived Cryptosporidium parvum oocysts, and then treated with drugs with specific modes of action against protozoans. Dependent on the specific aim the test animals will be sacrificed 11 to 79 days after oocyst inoculation, and the extent of infection determined histologically by analysis of hematoxylin and eosin stained sections of the small and large intestine. The severity of infection in a test drug-treatment group will be compared with that in immunosuppressed non-medicated control and drug-positive control groups. In addition to evaluating individual drugs for anticryptosporidial activity, drug combinations will be evaluated for synergistic anticryptosporidial activity in the immunosuppressed rat model. The principal aims are to identify drugs with anticryptosporidial activity and to characterize the conditions whereby these drugs can be an effective treatment for cryptosporidiosis and the eradication of the parasite.