EVALUATION OF DRUGS FOR ANTICRYPTOSPORIDIAL ACTIVITY

药物抗隐孢子虫活性评价

• 批准号: 3148369
• 负责人: Jerold E. Rehg
• 金额: $ 16.69万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-07-01 至 1997-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3148369
• 关键词: Cryptosporidium; antiprotozoal agents; artificial immunosuppression; cryptosporidiosis; dexamethasone; drug screening /evaluation; histology; laboratory rat; microorganism disease chemotherapy; nonhuman therapy evaluation

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.

隐孢子虫病是公认的艾滋病患者的肠道疾病， 其他免疫功能低下的宿主，迫切需要有效的治疗， needed. 长期目标是确定慢性 艾滋病患者的隐孢子虫病。 提出的具体目标 研究是为了确定适当的剂量，治疗持续时间和 治疗方案，使个别药物或药物 根除或控制隐孢子虫感染的组合， 免疫抑制大鼠 将雌性Sprague-Dawley大鼠（225-250 gm） 地塞米松（0.25 mg/kg/天）免疫抑制10天，感染 用标准剂量的牛源隐孢子虫卵囊，和 然后用对原生动物具有特定作用模式的药物进行治疗。 根据具体目的，将处死11至79只试验动物 卵囊接种后30天，并确定感染程度 通过苏木精和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 未给药对照组和药物阳性对照组。 除了 评价抗隐孢子虫药物的活性，药物 将评价组合的协同抗隐孢子虫活性 免疫抑制大鼠模型中。 主要目的是确定 具有抗隐孢子虫活性的药物， 由此这些药物可以是隐孢子虫病的有效治疗， 消灭寄生虫