AL +3 NEUROBEHAVIORAL TOXICITY: CONTRIBUTING FACTORS

长期接触铝(Al)已被证明是导致 进行性恶化的脑病(透析性脑病和 可能患有阿尔茨海默氏型老年痴呆症)和骨病(透析 骨营养不良症)。影响吸收和吸收的因素 铝的积累，以及铝被处理的基本机制 身体并没有被很好地理解。拟议的研究将澄清这些角色 铝的形式，肾功能受损，胃完整性改变，以及 缺钙对兔铝吸收的影响。急性生物利用度 最初将进行研究，以评估每一项 上述变量对铝的药代动力学(吸收、分布和速率 淘汰赛)。铝遗嘱急性生物利用度研究结果 然后应用于亚慢性铝暴露研究，以确定 影响铝动力学的因素也影响铝在土壤中的积累 组织与铝神经行为毒性的发展。艾尔将会是 给兔口服可溶和不溶的有机和无机物 盐，以评估铝的形式的贡献。慢性肾脏 部分肾动脉结扎可造成兔肾功能损害。 急性服用阿司匹林会改变胃的完整性 停职。亚慢性维护会导致缺钙 以缺钙饮食为生。血清铝的标准药代动力学分析 将在急性铝剂量后进行，以及许多生理上的 将评估措施(行为、铝组织水平和神经病理学) 在亚慢性铝剂量后。我们亦会进行研究，以 阐明控制铝吸收的一些基本过程和 希望这些结果将有助于解释 在急性和亚慢性研究中获得的结果，并提供见解 进入铝通过膜的机制。大鼠肠道 切片将用来阐明铝的吸收机制。 经典肾脏药理制剂(兔肾切片和 Sperber鸡技术)将被用来阐明 阿尔淘汰赛。结果应提供有益于 选择一种基于铝的产品时使用，并接近 治疗和预防铝蓄积和由此引起的疾病。

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.