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OPIOID DEPENDENCY AND AIDS

阿片类药物依赖和艾滋病

基本信息

批准号：
2118310
负责人：
RONALD Y CHUANG
金额：
$ 47.21万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-08-01 至 1999-12-31
项目状态：
已结题

项目摘要

The primary cause of AIDS (acquired immunodeficiency syndrome) in humans has been identified as the infection of cells of the immune system by the human immunodeficiency virus (HIV-1 or HIV-2) through sexual contact or the exchange of blood. Individuals infected with HIV vary in their rate of development of AIDS, suggesting that co-factors other than the virus itself are involved in influencing the rate of disease progression. Opioid addicts make up a significant portion of the AIDS population. The long-term objective of our research is to determine whether the cyclical effects induced by short-acting opioids on an individuals immune system will alter the process from initial viral exposure to the development of full-blown AIDS. Using the simian immunodeficiency virus (SIV) and rhesus monkeys (Macaca mulatta) as an animal model system for studying viral pathogenesis and AIDS, the objective of the current proposal is to continue our previous studies in evaluating the effects of morphine dependence on the viremia and on disease development after inoculation with SIVmac239, a molecular clone of SIV. Special reference will be made to mutations of the virus and sequential alterations in CD8+ functions. The specific aims are (l) to study the effects of oral methadone treatment versus the effects of morphine treatment on simian AIDS progression, (2) to compare the effects of morphine treatment versus the effects of morphine with the use of the antagonist naltrexone, and (3) to evaluate immunosuppressive treatment of the progression of the viremia using cyclosporin A with and without the administration of morphine. Methods of investigation include evaluation of the effects of SIV infection and opioid treatment on polymorphonuclear cell (PMN) chemotaxis and phagocytosis activities, neutralizing antibody titers, T-helper cell and natural killer cell functions, CD8+ antiviral activity, the occurrence of escape viral mutants, and SIV-induced programmed cell death. Recognizing the importance of opioids in AIDS pathogenesis and the use of effective drug abuse treatments such as methadone maintenance may result in the conception of new strategies of research and treatment for combatting the disease.

人类艾滋病(获得性免疫缺陷综合征)的主要原因已经被确认为免疫系统细胞的感染人类免疫缺陷病毒(HIV-1或HIV-2)经性接触或血液的交换。感染艾滋病毒的人的感染率各不相同艾滋病的发展，这表明除了病毒之外的其他辅助因素其本身参与了影响疾病进展的速度。阿片成瘾者占艾滋病人口的很大一部分。这个我们研究的长期目标是确定周期性的短效阿片类药物对个体免疫系统的影响将改变从最初接触病毒到发展为全面感染艾滋病。使用猴免疫缺陷病毒(SIV)和恒河猴(猕猴 Mulatta)作为研究病毒致病机制的动物模型系统艾滋病，目前提议的目标是继续我们以前的评价吗啡依赖对病毒血症影响的研究以及接种SIVmac239分子后的疾病发展 SIV的克隆。将特别提及病毒的突变。 CD8+功能的序贯变化。具体目标是(L) 目的：研究口服美沙酮的疗效与口服美沙酮的疗效。吗啡治疗对猴艾滋病进展的影响，(2)疗效比较吗啡治疗与吗啡效果之间的关系拮抗剂纳曲酮，以及(3)评价免疫抑制治疗环孢菌素A治疗病毒血症的进展注射吗啡。调查方法包括评估 SIV感染和阿片类药物治疗对中性粒细胞的影响中性粒细胞(PMN)趋化和吞噬活性，中和抗体滴度，T辅助细胞和自然杀伤细胞功能，CD8+抗病毒活性、逃逸病毒突变的发生和SIV诱导程序性细胞死亡。认识到阿片类药物在艾滋病中的重要性发病机制和有效药物滥用治疗的使用，如美沙酮维持可能导致新战略的构想与疾病作斗争的研究和治疗。