AL +3 NEUROBEHAVIORAL TOXICITY: CONTRIBUTING FACTORS

长期暴露于铝（Al）已被证明有助于 进行性恶化的脑部疾病（透析性脑病和 可能的阿尔茨海默型老年痴呆症）和骨病（透析 骨营养不良）。 影响吸收的因素， 铝的积累，以及铝处理的基本机制， 身体不太了解。 拟议的研究将阐明 铝的形式，肾功能受损，胃完整性改变，和 缺钙对家兔铝吸收的影响 急性生物利用度 首先将进行研究，以评估每一项措施的影响， 上述变量对Al药代动力学（吸收、分布和速率）的影响 消除）。 Al的急性生物利用度研究结果将 然后应用于亚慢性铝暴露研究，以确定 影响Al动力学的因素也影响Al在 组织和铝神经行为毒性的发展。 艾尔会 以可溶性和不溶性有机和无机形式经口给予家兔 盐，以评估铝的形式的贡献。 将通过部分肾动脉结扎在兔中产生损伤。 急性服用阿司匹林会改变胃的完整性 悬浮液 缺钙会产生亚慢性维持 缺钙饮食 血清Al的标准药代动力学分析 将在急性Al给药后进行， 将评估指标（行为、Al组织水平和神经病理学） 在亚慢性Al给药后。 还将进行研究， 阐明了控制铝吸收的一些基本过程， 消除，希望这些结果将有助于解释 急性和亚慢性研究中获得的结果， 铝通过膜的机制。 大鼠肠 切片将被用来阐明铝吸收的机制。 经典的肾脏药理学制剂（来自兔和 Sperber鸡技术）将用于阐明 人工智能消除。 结果应提供有益的信息， 选择铝基产品时，将使用和方法， 治疗和预防铝积累及其引起的疾病。

Prolonged exposure to aluminum (Al) has been shown to contribute to progressive deteriorating brain disease (dialysis encephalopathy and possible senile demetia of the Alzheimer's type) and bone disease (dialysis osteodystrophy). The factors contributing to the absorption and accumulation of Al, and the basic mechanisms by which Al is handled by the body are not well understood. The proposed studies will clarify the roles of the form of Al, impaired renal function, altered gastric integrity, and calcium deficiency on Al absorption in rabbits. Acute bioavailability studies will initially be conducted to assess the influence of each of the above variables on Al pharmacokinetics (absorption, distribution and rate of elimination). Results from the acute bioavailability studies of Al will then be applied in subchronic Al exposure studies to determine if the factors influencing Al kinetics also influence the accumulation of Al in tissues and the development of Al neurobehavioral toxicity. Al will be given orally to rabbits as soluble and insoluble organic and inorganic salts to assess the contribution of the form of Al. Chronic renal impairment will be produced in rabbits by partial renal arterial ligation. Stomach integrity will be altered by acute administration of aspirin suspension. Calcium deficiency will be produced by subchronic maintenance on a calcium deficient diet. Standard pharmacokinetic analyses of serum Al will be conducted following acute Al dosing, and numerous physiological measures (behavior, Al tissue levels and neuropathology) will be assessed following subchronic Al dosing. Studies will also be conducted to elucidate some of the basic processes controlling Al absorption and elimination, with the hopes that these results will help explain the results obtained in the acute and subchronic studies, and provide insight into the mechanisms by which Al passes throuh membranes. Rat intestinal slices will be used to elucidate the mechanisms of Al absorption. Classical renal pharmacology preparations (renal slices from rabbits and the Sperber chicken technique) will be used to elucidate the mechanisms of Al elimination. The results should provide information beneficial in selecting an Al based product when one is to be used and approaches to the treatment and prevention of Al accumulation and resultant diseases.