Newton001 Temporal profiling of cardiac autonomic changes following organophosphorus poisoning

Newton001 有机磷中毒后心脏自主神经变化的时间分析

• 批准号: MR/M026442/1
• 负责人: Julian Paton
• 金额: $ 5.2万
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FM026442%2F1
• 关键词: Newton001; Temporal; profiling; cardiac; autonomic

Organophosphorus (OP) compounds are the most widely used insecticides in many countries including Brazil, Egypt, India and USA. According to the latest reports, OP are responsible for the majority of poisonings, deaths and suicides attempts in Brazil. The latest Brazilian National System reporting on Toxico-Pharmacological Poisoning (SINITOX, 2009) indicated that the number of people poisoned by pesticides between 2001 and 2007 increased in 347% in a single State alone (Espirito Santo) compared to an equivalent period in previous years. This Brazilian State now has the second highest number of OP poisoning cases (5,512) within the south-east region of Brazil. OP compounds act by interfering with nerve cell communication by blocking an enzyme (acetyl cholinesterase). This leads to disruption of both the central and peripheral nervous systems. The effects on the heart, circulation and breathing by OP are likely to contribute in a major way to their lethality. Although clinical signs of OP poisoning are well described, our understanding of the precise mechanisms and their time course is highly limited and it this we wish to study. This is important because it would reveal the most effective therapeutic treatment relative to the time after OP poisoning. Following OP exposure, clinical symptoms are classified into 3 stages: (i) acute crisis syndrome within the first few hours; (ii) an intermediate stage between 12-96 hours and (iii) a delayed nervous system dysfunction stage. We wish to understand how the heart, circulation and respiratory symptoms occur within the first two stages of OP poisoning, and whether these are worsened in conditions of pre-existing heart failure. We propose that the deleterious effects of OP poisoning immediately affect the peripheral nervous system controlling the heart, circulation and respiration, worsen with time and are exaggerated if the subject has pre-existing heart failure.

有机磷化合物是包括巴西、埃及、印度和美国在内的许多国家最广泛使用的杀虫剂。根据最新的报告，OP是巴西大多数中毒、死亡和自杀未遂事件的罪魁祸首。最新的巴西国家系统毒物-药理学中毒报告（SINITOX， 2009年）表明，与前几年同期相比，2001年至2007年间，仅在圣埃斯皮里图州一个州，农药中毒人数就增加了347%。这个州目前是巴西东南部地区OP中毒病例第二多的州（5,512例）。OP化合物通过阻断一种酶（乙酰胆碱酯酶）来干扰神经细胞的通讯。这会导致中枢和周围神经系统的破坏。OP对心脏、循环和呼吸的影响可能是其致命的主要原因。尽管对OP中毒的临床症状有很好的描述，但我们对其确切机制及其时间过程的了解非常有限，这是我们希望研究的。这很重要，因为它将揭示相对于OP中毒后的时间最有效的治疗方法。接触OP后，临床症状分为3个阶段：(i)最初几个小时内出现急性危象综合征；（ii）介于12-96小时之间的中间阶段和（iii）延迟的神经系统功能障碍阶段。我们希望了解心脏、循环和呼吸系统症状是如何在OP中毒的前两个阶段发生的，以及这些症状是否在先前存在心力衰竭的情况下恶化。我们认为OP中毒的有害影响会立即影响控制心脏、循环和呼吸的周围神经系统，随着时间的推移而恶化，如果受试者已经患有心力衰竭，则会被夸大。

项目成果

Methamidophos, an Organophosphorus Insecticide, Induces Pro-aggressive Behaviour in Mice.

• DOI: 10.1007/s12640-017-9750-9
• 发表时间: 2017-10
• 期刊: Neurotoxicity research
• 影响因子: 3.7
• 作者: do Nascimento CP;Maretto GX;Marques GLM;Passamani LM;Abdala AP;Schenberg LC;Beijamini V;Sampaio KN
• 通讯作者: Sampaio KN