PREVENTION OR REVERSAL OF PARAQUAT TOXICITY IN ANIMALS

百草枯是一种广泛使用的除草剂， 肺纤维化的患者， 市售的浓缩溶液。 许多解毒剂 提出的治疗方式未能改变过程， 临床治疗主要依靠强化支持性护理。 然而，在这方面， 最近使用的一种治疗方式，但没有充分测试， 对照人体研究是每天重复进行血液灌流， 百草枯已从体内清除。 其功效可能取决于 清除体内百草枯并保持其血药浓度， 这些化合物低于那些允许百草枯被植物主动吸收的化合物。 肺细胞导致其最终的破坏和取代 纤维组织 本研究计划旨在确定 控制条件，无论重复活性炭血液灌流是否改变 百草枯对小猎犬的毒性过程 肺部疾病的临床体征 将评价毒性以及实验室检查表现， 尸检中肺、肾、肝和 大脑功能和结构 血液灌流的并发症将 百草枯中毒程序的成本效益 测定 在第二组实验中，一种新的方法， 快速从百草枯中毒的小鼠体内清除大量百草枯， 开发和测试。 这将通过产生鼠 产生高特异性单克隆抗体杂交瘤， 对百草枯的亲和力 这些抗体会被木瓜蛋白酶缩小 消化以产生可被肾脏消除的Fab片段。 抗百草枯Fab片段在预防致死性或致死性疾病中的功效 肺纤维化，并对百草枯组织分布将 在静脉注射百草枯致死的小鼠中测定。 的 这项研究的最终意义超出了对 这两种技术从体内清除百草枯的能力， 其他麻醉品

Paraquat, a widely used herbicide, has caused hundreds of fatalities from pulmonary fibrosis in patients who have ingested as little as a mouthful of the concentrated solution that is marketed commercially. Many antidotes proposed as therapeutic modalities have failed to alter the course and clinical management rests largely on intensive supportive care. However, one therapeutic modality recently employed but not tested adequately in controlled human studies is that of repeated daily hemoperfusion done until paraquat has been removed from the body. Its efficacy probably depends on its removing paraquat from the body and keeping plasma concentration of the compound below those that allow active uptake of paraquat by the pneumocytes leading to their ultimate destruction and replacement by fibrous tissue. This research plan has been designed to determine under controlled conditions whether or not repeated charcoal hemoperfusion alters the course of paraquat toxicity in the Beagle. Clinical signs of pulmonary toxicity will be evaluated as well as laboratory test manifestations and changes on post-mortem examination in pulmonary, renal, hepatic and cerebral function and structure. Complications of hemoperfusion will be assessed and the cost benefit of the procedure in paraquat poisoning determined. In the second set of experiments, a novel approach to the rapid removal of large amounts of paraquat from paraquat-poisoned mice will be developed and tested. This will be effected by producing murine hybridomas that produce monoclonal antibodies of high specificity and affinity for paraquat. These antibodies will be reduced in size by papain digestion to produce Fab fragments which can be eliminated by the kidney. The efficacy of the antiparaquat Fab fragments in preventing lethality or the pulmonary fibrosis, and on paraquat tissue distribution will be determined in mice given a lethal intravenous injection of paraquat. The ultimate significance of this research extends beyond examination of the ability of these two techniques to remove paraquat from the body to many other intoxicants.