MODIFICATION OF ORGANOPHOSPHORUS NEUROPATHY

长期目标是提供一种减少延误的方法 暴露于某些有机磷的人和动物的神经病。AS 有机磷化合物被广泛应用于今天的农业和 行业，意外事故和职业风险相对较高 曝光。尽管有治疗急性中毒的解毒剂，但没有 已经为不可逆转的神经病开发了特殊的治疗方法 发生在接触其中一些化合物的几周到几个月后。 正如最近在我们的实验室和其他实验室证明的那样，肾上腺皮质激素 荷尔蒙似乎很有希望作为药物来提供一些缓和 有机磷化合物的迟发性神经毒性作用。vbl.使用 磷酸三原醇酯(TOTP)诱导鸡迟发性神经病的研究 将检测一种天然皮质激素的广泛饮食浓度， 皮质酮对这种迟发性神经病变的指标的影响，如 临床体征、组织病理学、电生理学和神经毒性酯酶 活动。我们将观察皮质酮本身对 通过监测异嗜性细胞/淋巴细胞比率、肝脏 功能和饲料效率。此外，作为拟议工作的一部分，一些 糖皮质激素的特性可能与 将检查有机磷诱导的迟发性神经病。这些遗嘱 包括皮质激素类型，通过使用矿物皮质激素 (脱氧皮质酮)，糖皮质激素(曲安奈德)，以及 同时具有这两种特性的皮质酮对TOTP诱导的延迟反应的影响 神经病。糖皮质激素可能改变新陈代谢 有机磷，从而提供保护，将被检查 一种前毒物所致迟发性神经病(TOTP)与 其活性代谢物(苯基盐基磷酸)在小鼠体内的诱导 皮质酮的存在。内源性类固醇可能是 替代外源性类固醇，因为有机磷具有抑制作用 类固醇生成，将通过尝试使用ACTH而不是 皮质酮保护鸟类免受TOTP诱导的迟发性神经病。 这些研究将增进我们对基本病机的理解。 有机磷诱导的迟发性神经毒性的机制，以及 希望能带来合理的治疗。

The long term objective is to provide a means for reducing delayed neuropathy in man and animals exposed to certain organophosphates. As organophosphorus compounds are widely used today in agriculture and industry, risk is relatively high for accidental and occupational exposure. Although antidotes for acute toxicities are available, no specific treatment has been developed for the irreversible neuropathy that occurs weeks to months after exposure to some of these compounds. As recently demonstrated in our laboratory and others, adrenocorticoid hormones appear promising as agents to provide some moderation of the delayed neurotoxic effects of organophosphorus compounds. Using triorthotolyl phosphate (TOTP) to induce delayed neuropathy in chickens, we will examine a wide range of dietary concentrations of a natural corticoid, corticosterone, for effects on indices of this delayed neuropathy, such as clinical signs, histopathology, electrophysiology and neurotoxic esterase activity. We will observe effects of the corticosterone per se on the health of the birds by monitoring the heterophil/lymphocyte ratio, liver function, and feed efficiency. Also, as part of the work proposed, some properties of corticoids that may be relevant in moderation of organophosphate induced delayed neuropathy will be examined. These will include type of corticoid, by using a mineralocorticoid (deoxycorticosterone), a glucocorticoid (triamcinolone), and corticosterone, which has both properties, to modify TOTP-induced delayed neuropathy. The possibility that corticoids may alter metabolism of organophosphates, thereby providing protection, will be examined by comparing delayed neuropathy induced by a protoxicant (TOTP) with that induced by its active metabolite (phenyl saligenin phosphate) in the presence of corticosterone. The possibility that endogenous steroid may be substituting for exogenous steroid, as organophosphates inhibit steroidgenesis, will be examined by attempting to use ACTH rather than corticosterone to protect the birds from TOTP-induced delayed neuropathy. These studies should enhance our understanding of the basic pathogenetic mechanisms in organophosphate-induced delayed neurotoxicity, and, hopefully, lead to rational therapy.