Enteric Elimination and Degradation of Oxalic Acid

在中国，大约有一百万例结石病被诊断出来。 美国每年都会出现草酸尿症，高草酸尿症被认为是 风险因素。我们的目标是减少草酸盐排泄的负担 草酸诱导的肾功能衰竭发病前肾脏 高草酸尿的侮辱，组织中草酸盐晶体的沉积，以及 草酸钙结石的形成。在这里提出的研究 代表着调查的继续，这些调查是为了 专门开发一种口服补充疗法，使用 底物专一性，肠道细菌草酸杆菌或其产品，用于 控制高草酸条件。到目前为止，我们的研究揭示了 肠道分泌/排泄的重要生理作用 肾与肾之间草酸排泄平衡的改变途径 以及肠道排泄途径。我们已经证明了细胞裂解物 草酸杆菌的制备刺激了活跃的转运系统 除了参与酶促排出草酸外，还参与结肠草酸的排泄 在溶液中降解草酸盐。随后，我们展示了一个令人印象深刻的 草酸大鼠体内尿草酸排泄量的减少 应用微囊化草酸杆菌裂解物诱导肾功能衰竭 与安慰剂相比。目前的目标是生产一种治疗性的 最大限度地利用这两者的结合的补充 行动，以控制高草酸条件。 建议的商业应用： 一种有效的补充治疗方法的开发 控制高草酸状况是及时的。目前，有1家 数以百万计的肾结石患者，还有 其他与草酸有关的疾病，包括原发性高草酸尿 总是导致早年死亡的草酸诱导 肾衰竭。一种新型药物的临床应用潜力 减少尿草酸排泄的治疗策略具有广泛的基础 而且意义重大。

Approximately one million cases of stone disease are diagnosed in the United States every year and hyperoxaluria is considered to be a major risk factor. Our goal is to reduce the burden of oxalate excretion by the kidneys before the onset of renal failure caused by the oxalate-induced insults of hyperoxaluria, oxalate crystal deposition in tissue, and the formation of calcium oxalate stones. The studies proposed here represent a continuation of investigations that were initiated to specifically develop an oral supplementation therapy, using the substrate-specific, gut bacteria Oxalobacter or its products, for the control of hyperoxaluric conditions. Thus far, our studies have revealed the important physiological role of intestinal secretory/excretory pathways in shifting the balance of oxalate excretion between the renal and enteric routes of elimination. We have shown that a cell lysate preparation from Oxalobacter stimulated the active transport systems involved in colonic oxalate excretion in addition to enzymically degrading oxalate in solution. Subsequently, we showed an impressive reduction in urinary oxalate excretion in vivo, in rats with oxalate- induced renal failure by administering encapsulated Oxalobacter lysate compared to placebo. The present objective is to produce a therapeutic supplement which will maximally exploit the combination of these two actions in order to control hyperoxaluric conditions. PROPOSED COMMERCIAL APPLICATIONS: The development of an effective supplementation therapy for the control of hyperoxaluric conditions is timely. Currently, there are 1 million patients with kidney stone disease and there are patients with other oxalate-associated diseases, including primary hyperoxaluria which invariably results in death at an early age due to oxalate-induced kidney failure. The potential for the clinical application of a novel treatment strategy to reduce urinary oxalate excretion is broad-based and highly significant.