25,26(OH)2D3: EFFECT ON METABOLISM OF 1,25(OH)2D

本研究的长期目标是评估临床 25，26-二羟维生素D（25，26（OH）2D 3）治疗糖尿病疗效观察 高钙三醇血症如原发性甲状旁腺功能亢进， 结节病、淋巴瘤引起的高钙血症和吸收性 高钙尿症 具体目标是：1）确定 25，26（OH）2D 3的最佳剂量和给药时间， 血清1，25-二羟维生素D（1，25（OH）2D）的减少， 2）探讨25，26（OH）_2D_3-的作用机制。 在动物模型中介导的血清1，25（OH）2D减少;和 3)评价25，26（OH）2D 3给药的有效性 对于患有以高血压为特征的各种疾病状态的患者， 循环1，25，（OH）2D浓度和高钙血症， 高钙尿症或两者。 初步调查显示， 25，26（OH）2D 3的量具有显著增加 降低1，25（OH）2D的循环浓度， 维生素D的生理活性形式，同时证明 很少或没有生物活性。 这一观察将是 通过给予不同剂量的25， 26（OH）2D 3给药不同时间间隔， 血清1，25，（OH）2D。 研究将扩展到犬类 检查通过什么机制（即，增加的代谢 清除、合成减少或两者兼而有之）25，26（OH）2D 3促进 血清1，25（OH）2D浓度降低。 这将是 通过给予微量的放射性1， 在适当的25，26（OH）2D 3之前和之后，给予犬25（OH）2D 3 给药和定量放射性的血浆消失。 从这些研究中，原发性高血压患者 甲状旁腺功能亢进，结节病，淋巴瘤诱发 高钙血症和吸收性高钙尿症将被收治， 一般临床研究中心，并接受基本的 钙稳态的评价，而在恒定的代谢 25，26（OH）2D 3给药前后的饮食。 如果有正当理由， 1，25（OH）2D 3清除率和合成率的评估可 也可以获得。 这些研究可能表明， 一定量的25，26（OH）2D 3可有效降低1，25，（OH）2D 手术（如原发性甲状旁腺功能亢进）时的浓度， 或药物治疗，如类固醇（例如结节病或淋巴瘤）， 禁忌。 肾结石患者的类似研究 疾病应该披露应该披露维生素的真实程度- 肠钙吸收依赖性 高钙尿症

The long term objective of this study is to assess the clinical efficacy of 25, 26-dihydroxyvitamin D (25, 26(OH)2D3) in treating hypercalcitriolemic states such as primary hyperparathyroidism, sarcoidosis, lymphoma induced hypercalcemia and absorptive hypercalciuria. The specific aims are 1) to determine the optimum dose and length of dosing of 25, 26(OH)2D3 to maximize reduction of serum 1, 25-dihydroxyvitamin D (1, 25(OH)2D) in an animal model; 2) to determine the mechanism of 25, 26(OH)2D3- mediated reduction of serum 1, 25(OH)2D in an animal model; and 3) to evaluate the effectiveness of 25, 26(OH)2D3 administration to patients with various disease states characterized by high circulating 1, 25,(OH)2D concentrations and hypercalcemia, hypercalciuria, or both. Preliminary investigations have disclosed that pharmacologic amounts of 25, 26(OH)2D3 have a unique ability to significantly reduce the circulating concentration of 1, 25(OH)2D, the physiologically active form of vitamin D, while demonstrating little or no biological activity of its own. This observation will be further investigated by administering various doses of 25, 26(OH)2D3 to rats for different intervals of time and measuring serum 1, 25,(OH)2D. Studies will then be extended to the canine to examine by what mechanism (i.e., increased metabolic clearance, decreased synthesis or both ) 25, 26(OH)2D3 promotes a reduction in serum 1, 25(OH)2D concentration. This will be accomplished by administering a trace dose of radioactive 1, 25(OH)2D3 to dogs, before and after appropriate 25, 26(OH)2D3 dosing, and quantifying the plasma disappearance of radioactivity. Form these studies, patients with inoperative primary hyperparathyroidism, sarcoidosis, lymphoma-induced hypercalcemia and absorptive hypercalciuria will be admitted to the General Clinical Research Center and undergo a basic evaluation of calcium homeostasis while on a constant metabolic diet before and after 25, 26(OH)2D3 dosing. If warranted, assessment of 1, 25(OH)2D3 clearance and synthetic rates can also be obtained. These studies may indicate that pharmacologic amounts of 25, 26(OH)2D3 are effective in lowering 1, 25,(OH)2D concentration where surgery (e.g. primary hyperparathyroidism), or drug therapy such as steroids (e.g. sarcoidosis or lymphoma) is contraindicated. Similar studies in patients with renal stone disease should disclose should disclose the true extent of vitamin- d dependency of intestinal calcium absorption in absorptive hypercalciuria.