Effects of Stretch on IC and Normal Urothelia

描述(摘自申请人摘要)：间质性膀胱炎(IC) 患者通常表现为极端的尿频、尿急和盆腔症状 疼痛。它有10：1的女性：男性占主导地位。因为病理生理学 IC的情况不清楚，治愈仍然难以捉摸，治疗选择是 很大程度上无效。即使是IC的诊断也存在争议。一个目标 诊断标准为术后膀胱镜下见肾小球 麻醉下膀胱积水(拉伸)。最近的数据对此提出了质疑 这一过程的诊断特异性是因为对照的水胀性 膀胱导致结节。根据调查人员的初步调查 数据显示IC尿路对牵拉反应显著 在膀胱镜下的表现、尿肝素水平与对照组不同 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.在液体扩张后出现的膀胱聚集物 符合NIH-IC症状标准(NISC)。2.男性慢性阻塞性肺病患者 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有水膨胀后的肾小球，而男性 使用CPPS而不使用NISC则不会。这一观察结果将进一步加强 与NISC的联合企业集团。3.部分NISC患者病情好转 有症状的充气后和改善的程度与 尿液标志物(APF、HB-EGF、ATP)的变化。4.IC的体外拉伸 尿路上皮细胞导致ATP、HBEGF升高和APF活性降低 与伸展的对照细胞相比。5.P2 X1表达增强 和P2X3ATP受体在IC中与对照膀胱尿路上皮和 上皮下层。这个项目是独一无二的，因为它将临床和实验室联系起来 用于检验IC尿路不同反应的中心假设的数据 伸展一下。只有人类样本将被用于提供最佳的临床相关性。 这项研究的发现将澄清目前的诊断困境 肾小球对IC诊断的特异性及治疗方案的确定 氢气膨胀的效果。此外，这项研究将探索令人兴奋的 一项新发现：拉伸的IC细胞释放的ATP明显更高 与对照组相比。三磷酸腺苷可能参与膀胱的伤害性感受。尿路上皮 因此，拉伸似乎是诊断、治疗中的一个重要考虑因素 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.