Biomedical Sciences Department, Dstl Porton Down, Salisbury, Wiltshire SP4 0JQ, UK.
Chem Biol Interact. 2010 Sep 6;187(1-3):304-8. doi: 10.1016/j.cbi.2010.02.020. Epub 2010 Feb 20.
The physiological effects of human plasma-derived butyrylcholinesterase (huBuChE) administration and its modulation of the effects of percutaneous VX challenge are poorly understood. Percutaneously administered nerve agents are more slowly absorbed than inhaled agents; consequently, signs of poisoning occur later, with a longer duration. Telemetry was used to monitor heart rate, EEG, temperature and activity in guinea-pigs. Treatment with huBuChE at 30 or 120 min following percutaneous VX challenge ( approximately 2.5 x LD(50)) provided 100% protection from lethality. When huBuChE administration was delayed until the onset of observable signs of poisoning only 1 out of 6 animals survived to the end of the experiment at 7 days. This study adds to the body of evidence demonstrating the efficacy of huBuChE in animals by describing the successful therapeutic use of a protein bioscavenger as a post-exposure treatment against dermal exposure to VX up to 2h post-exposure. This study simultaneously used telemetric methods to show that the efficacy of huBuChE is linked to the prevention of detrimental physiological changes observed in control VX-treated animals. Post-exposure therapy is a promising additional indication for the concept of use of this material, and one that has particular relevance in a civilian exposure scenario.
人血浆来源的丁酰胆碱酯酶（huBuChE）给药的生理效应及其对经皮 VX 挑战效应的调节作用尚未完全阐明。经皮给予的神经毒剂比吸入的毒剂吸收更慢；因此，中毒迹象出现较晚，持续时间更长。遥测技术用于监测豚鼠的心率、脑电图、体温和活动。在经皮 VX 挑战（约 2.5 x LD(50)）后 30 或 120 分钟给予 huBuChE 治疗，可提供 100%的致死保护。当 huBuChE 给药延迟到可观察到中毒迹象出现时，只有 6 只动物中的 1 只存活到 7 天实验结束。本研究通过描述生物清除蛋白作为一种暴露后治疗，在暴露后 2 小时内成功治疗经皮 VX 暴露，为 huBuChE 在动物中的疗效提供了更多证据。本研究同时使用遥测方法表明，huBuChE 的疗效与其预防对照 VX 处理动物中观察到的有害生理变化有关。暴露后治疗是该材料使用概念的一个有前途的附加适应症，在平民暴露场景中具有特别重要的意义。
