SUCCIMER REDUCTION OF TISSUE LEAD (PB) & TOXICITY IN MONKEYS

目的：测定琥珀酰螯合剂的疗效 治疗减轻猴子的铅中毒，并确定 内源性铅的再活化。 本研究评估 神经行为和生理终点以及临床平行 儿童试验。 结果我们开始分析大量的 1997年收集的行为和生理数据， 验证螯合剂如琥珀酰亚胺的功效， 减少儿童体内铅的储存，但减轻神经行为 和靶器官毒性。 将猴子的治疗组分为 不接触铅（对照组），每天摄入铅一年， 两年的每日铅摄入量 铅管理从出生开始。 我们维持猴子在目标血铅水平上摄入铅 在铅摄入期间，35 g Pb/d的浓度，其福尔斯接近 计划中的琥珀酰亚胺临床试验的中期。 猴子接受 琥珀酰亚胺的两种处理方案分别在约12和15 月龄。 两个年龄组的儿童 儿童重返铅污染环境的案例 螯合治疗后。 我们监测琥珀酰亚胺的疗效， 通过广泛的行为治疗来逆转神经行为缺陷， 在三种疗法的过程中以及之后进行的测试 完成所有螯合，后者是为了评估长期 琥珀酰亚胺疗法对神经行为过程的功效。 我们使用 铅诱导的血红素生物合成途径的改变是敏感的 全身器官铅毒性的生物标志物。 一个既定 稳定的铅同位素技术确定铅的去除， 骨骼和软组织储存。 K-X射线荧光技术 评估由于以下原因导致的骨骼铅减少的长期变化 青少年猴子的螯合作用。 结果应提供有价值的数据 琥珀酰亚胺缓解神经行为和靶向的功效 儿童器官毒性。 今后的方向继续收集 分析所有的行为和生理数据 关键词铅， 猴子，螯合作用，琥珀酰亚胺，学习，社会行为，活动， 稳定同位素

OBJECTIVE: To determine the efficacy of succimer chelation therapy in alleviating lead toxicity in monkeys and to determine the endogenous sources of lead remobilized. This study evaluates neurobehavioral and physiological endpoints and parallels clinical trials in children. RESULTS We began analyzing vast amounts of behavioral and physiological data collected in 1997 There is a need to validate the efficacy of chelation agents such as succimer not only to reduce body lead stores in children but to alleviate neurobehavioral and target organ toxicity. Treatment groups of monkeys are divided into no lead exposure (controls), one year of daily lead intake, and two years of daily lead intake. Lead administration begins at birth. We maintain monkeys receiving lead at a target blood lead concentrations of 35 g Pb/d during lead intake, which falls near the midrange of the planned clinical trials of succimer. Monkeys receive two treatment regimes of succimer beginning at approximately 12 and 15 months of age. The groups given lead until two years of age parallel cases in which children return to lead contaminated environments following chelation therapy. We monitor the efficacy of succimer in reversing neurobehavioral deficits with a broad range of behavioral tests administered over the course of the three therapies and after completion of all chelations, the latter to evaluate the long term efficacy of succimer therapy on neurobehavioral processes. We use lead-induced alterations in the heme biosynthetic pathway as sensitive biomarkers of systemic organ lead toxicity. An established stable-lead isotope technique determines the removal of lead from skeletal and soft tissue stores. K-X-ray fluorescence techniques assess long-term changes in reduction of skeletal lead due to chelation in adolescent monkeys. Results should provide valuable data on the efficacy of succimer to alleviate neurobehavioral and target organ toxicity in children. FUTURE DIRECTIONS To continue collecting and analyzing all behavioral and physiological data. KEY WORDS lead, monkeys, chelation, succimer, learning, social behavior, activity, stable isotopes