Effects of Stretch on IC and Normal Urothelia

描述（改编自申请人摘要）：间质性膀胱炎（IC） 患者通常表现为极度尿频、尿急和骨盆疼痛。 痛苦它有10：1的女性：男性优势。由于病理生理 IC的情况尚不清楚，治愈仍然难以捉摸，治疗方案 大部分无效。甚至IC的诊断也存在争议。客观 诊断标准是膀胱镜下出现肾小球， 麻醉下膀胱水扩张（拉伸）。最近的数据质疑了 该手术的诊断特异性，因为控制性水肿 膀胱导致肾小球形成。根据调查人员初步的 数据显示IC尿路上皮对牵拉的反应显著 与对照组相比，膀胱镜检查结果、尿肝素水平 结合表皮生长因子样生长因子（HB-EGF），抗增殖 活性（APF）和三磷酸腺苷（ATP），他们建议测试这些 假设：1.膀胱肾小球，出现在水扩张后， NIH-IC症状标准（NISC）。2.男性慢性 非细菌性前列腺炎（前列腺炎III级或慢性盆腔疼痛 综合征，CPPS）和NISC具有水扩张后肾小球，而男性 而没有NISC的情况下则不会。这一意见将进一步加强 肾小球与NISC的相关性。3.一些NISC患者改善 液压扩张后的功能和改善程度与 尿标志物（APF、HB-EGF和ATP）的变化。4. IC的体外拉伸 尿路上皮细胞导致ATP、HBEGF增加和APF活性降低 与对照组细胞相比。5. P2X1的表达增加 IC中的P2X3和P2X3 ATP受体与对照膀胱尿路刺激相比， 亚甲状腺素这个项目是独一无二的，因为它连接临床和实验室 数据来检验中心假设，IC尿路上皮反应不同， 伸展。仅使用人体样本以提供最佳临床相关性。 这项研究的结果将澄清目前的诊断困境， 肾小球的特异性诊断IC和确定治疗 水扩张的功效。此外，这项研究将探索令人兴奋的 新发现，拉伸IC细胞释放的ATP明显高于 与对照相比。ATP可介导膀胱的伤害性感受。尿路上皮 因此，牵张似乎是诊断、治疗 和IC的病理生理学。

DESCRIPTION (Adapted from the Applicant's Abstract): Interstitial cystitis (IC) patients typically present with extreme urinary frequency, urgency and pelvic pain. It has a 10:1 female:male predominance. Since the pathophysiologic picture of IC is unclear, cure remains elusive and treatment options are largely ineffectual. Even the diagnosis of IC is controversial. An objective diagnostic criterion is the cystoscopic appearance of glomerulations after bladder hydrodistention (stretch) under anesthesia. Recent data disputed the diagnostic specificity of this procedure because hydrodistention of control bladders resulted in glomerulations. Based on the investigators' preliminary data which showed that IC urothelia responded to stretch significantly differently than controls in cystoscopic appearance, levels of urinary heparin binding epidermal growth factor-like growth factor (HB-EGF), antiproliferative activity (APF), and adenosine triphosphate (ATP), they propose to test these hypotheses: 1. Bladder glomerulations, which appear after hydrodistention, are specific for NIH-IC symptoms criteria (NISC). 2. Male patients with chronic non-bacterial prostatitis (prostatitis class III or chronic pelvic pain syndrome, CPPS) and NISC have post-hydrodistention glomerulations whereas males with CPPS and no NISC do not. This observation would further strengthen the association of glomerulations with NISC. 3. Some NISC patients improve symptomatically after hydrodistention and degree of improvement correlates with changes in urinary markers (APF, HB-EGF and ATP). 4. In vitro stretch of IC urothelial cells results in increased ATP, HBEGF and decreased APF activity compared to stretch of control cells. 5. There is increased expression of P2X1 and P2X3 ATP receptors in IC compared to control bladder urothelium and suburothelium. This project is unique because it links clinical and laboratory data to test the central hypothesis that IC urothelia respond differently to stretch. Only human samples will be used to provide optimal clinical relevance. Findings from this study will clarify the current diagnostic dilemma regarding specificity of glomerulations for diagnosing IC and determine the therapeutic efficacy of hydrodistention. Furthermore, this study will explore the exciting new discovery that ATP released by stretched IC cells is significantly higher compared to controls. ATP may mediate nociception in the bladder. Urothelial stretch thus appears to be an important consideration in diagnosis, treatment and pathophysiology of IC.