INTEGRATED CLINICAL & BASIC STUDIES OF HUMAN TOXICOLOGY

综合临床

• 批准号: 3095936
• 负责人: PHILIP S GUZELIAN
• 金额: $ 41.4万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-08-01 至 1990-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3095936
• 关键词: human subject; toxicology

This Program Project is comprised of Clinicians, Clinician/Scientists, and Basic Scientists working to bring together the scientific and clinical resources needed to investigate directly in humans or in human tissues the effects of toxic substances in the environment. This departure from standard approaches to investigation of the toxicology of environmental agents is based on the recognition that the relevance to man of toxicity testing in animals or in vitro systems can be established with certainty only by making critical experiments on humans or on human derived tissues. In Project #1 the characteristics and distribution among human liver samples of purified human liver cytochromes P-450 in patients. Project #3 proposes to use similar biochemical and molecular biologic techniques to investigate a human liver aldo-keto reductase involved in the metabolism of the organochlorine pesticide, chlordecone. In Project #4, biochemical and cytological probes will be used to investigate the mechanisms of toxicity of organophosphates on the nervous system. In Project #5, biochemical and micropuncture techniques will be used to examine mechanisms of glomerular vs. tubular injury by metals. Project #6 is the Clinical Research Core comprised of medical specialty units (neuro-psychiatric, pulmonary, cardiovascular, liver, renal, dermatology, urology, analytical laboratories) capable of evaluating organ specific toxicity. The Core also is comprised of patient populations available for investigation. These include workers with documented over-exposure to cadmium and patients with documented allergic dermatitis to environmental agents. The proposed studies are expected to provide new information about clinical manifestations of toxicity due to environmental agents, insight into the mechanism of injury by these agents, and a greater understanding of some detoxification of enzyme systems. Moreover, we expect this Program to exemplify the utility involving clinical medicine in the study of human toxicology.

该计划项目由临床医生、 临床医生/科学家和基础科学家致力于将 汇集所需的科学和临床资源 直接研究人体或人体组织的影响 环境中的有毒物质。 这种偏离标准 环境毒理学研究方法 代理是基于这样的认识：与人的相关性 可以建立动物或体外系统的毒性测试 只有通过对人类或其他动物进行严格的实验才能确定 人类来源的组织。 项目#1 的特点和 纯化的人肝脏的人肝脏样本之间的分布 患者体内的细胞色素 P-450。 项目#3建议使用类似的 生物化学和分子生物学技术来研究 人肝醛酮还原酶参与代谢 有机氯农药，十氯酮。 在项目#4中，生化 和细胞学探针将用于研究其机制 有机磷酸酯对神经系统的毒性。 项目中 #5，生化和微穿刺技术将用于 检查金属对肾小球和肾小管损伤的机制。 项目 #6 是临床研究核心，包括医学 专业科室（神经精神科、肺科、心血管科、 肝脏、肾脏、皮肤科、泌尿科、分析实验室） 能够评估器官特异性毒性。 核心也是 由可供调查的患者群体组成。 其中包括有记录表明过度接触镉的工人和 患有环境过敏性皮炎的患者 代理。 拟议的研究预计将提供新的 有关毒性临床表现的信息 环境因素，深入了解这些因素造成的伤害机制 剂，以及对一些解毒作用有更深入的了解 酶系统。 此外，我们希望该计划能够体现 涉及临床医学在人类研究中的效用 毒理学。