NOVEL TREATMENT FOR CYSTINURIA AND STONES OF IMMOBILIZATION

该项目的总体目标是确定一种新的硫醇 复方(Rimatil)将比Thiola更有效和更安全 控制胱氨酸尿症和胱氨酸结石形成，并确定 一种新的二磷酸盐(阿伦磷酸)可能会防止结石的形成 长时间的制动。剂量-反应关系将被表征 为了证明利马替尔在降压方面比硫奥拉更有效 胱氨酸排泄物。A三年。利马替尔与硫奥拉的随机对照试验 将在半胱氨酸尿症患者中进行，每次调整剂量 以实现对胱氨酸排泄的最佳控制(250-400毫克/天)。 终点将是药物剂量和副作用概况，以及 预期利马替尔组将需要较低的剂量和改善 使用安全。采用卧床模式，延长结石形成时间 固定(或太空飞行)已经被证明是由于增加了 肾脏因骨质流失而排出的钙和磷。阿伦磷酸钠可能 防止尿钙和尿磷升高(和尿中 形成结石的钙盐饱和)通过抑制骨吸收。 该计划将在正常受试者身上进行测试，受试者将接受3周的 达拉斯的卧床休息和那些参加了为期17周的卧床休息研究的人 休斯敦。这些研究具有生物医学的重要性，因为它们可能会 改善对胱氨酸尿症的治疗，并导致AN的发展 太空旅行等过程中结石形成的有效对策 固定状态。

The overall goal of this project is to determine whether a new thiol compound (Rimatil) would be more effective and safer than Thiola in controlling cystinuria and cystine stone formations, and to ascertain if a new diphosphonate (alendronate) might prevent stone formation from prolonged immobilization. A dose response relation will be characterized in order to show that Rimatil is more effective than Thiola in lowering cystine excretion. A 3 yr. randomized trial between Rimatil and Thiola will be conducted in cystinuric patients, with the dose of each adjusted to achieve an optimum control of cystine excretion (250-400 mg/day). Endpoints will be drug dosage and side effect profile, with the expectation that Rimatil group would require a lower dose and improved safety of usage. Using bedrest model, stone formation during prolonged immobilization (or space flight) has been shown to be due to increased renal excretion of calcium and phosphate from bone loss. Alendronate might prevent the rise in urinary calcium and phosphate (and in urinary saturation of stone-forming calcium salts) by inhibiting bone resorption. This scheme will be tested in normal subjects undergoing 3 weeks of bedrest at Dallas and those participating in a 17-week bedrest study at Houston. These studies have biomedical importance, since they may allow improved treatment of cystinuria, and lead to the development of an effective countermeasure for stone-formation during space travel and other immobilization states.