Univ of Maryland Baltimore Interdisciplinary Research Center in Benign Urology

描述（由申请方提供）：OAB的病理生理学未知。虽然有提出的病因包括逼尿肌平滑肌和神经机制，膀胱尿路上皮细胞（布克）的潜在贡献OAB是一个新的调查途径。马里兰州大学良性泌尿科跨学科研究中心（UM-IRC）将进行一项计划研究，其中将从无尿失禁和无排尿症状的受试者（对照）和有OAB症状（急迫性尿失禁）的受试者中获得膀胱尿路上皮活检。将在项目负责人（Chai）和两名共同主要研究者（Birder、Keay）的实验室中研究来自这些活检的原代布克培养物。因为这些实验室已经有了独立的资金，所以UM-IRC采用了多PI方法。实验室研究的目的是获得初步的实验室数据，然后使用实验室客观指标作为主要结局，这些数据可以帮助下一项OAB试验具有统计学效力。将测量的布克的三种表型是细胞内多胺的表达、紧密连接蛋白的表达和通过响应于低渗和化学刺激的三磷酸腺苷（ATP）释放测量的细胞机械敏感性。早期的初步数据表明，在OAB布克中，所有这三种表型都发生了改变。在此规划阶段，UM-IRC将在三个实验室之间建立牢固的合作关系，这些实验室已经在基础膀胱尿路上皮生物学研究中非常活跃。在规划阶段，将使用一个咨询小组来管理UM-IRC。由于前两年最重要的因素是招募OAB和对照受试者接受膀胱尿路上皮活检，因此顾问小组将持续监测招募人数以及受试者安全性。UM-IRC将利用马里兰州大学的尿失禁和骨盆中心进行招募。目前有几项OAB临床试验正在进行中，这有助于本提案的招募。基于RFA的预算限制，将入组10例OAB受试者和10例对照受试者。UM-IRC将利用跨学科的方法进行将尿路上皮病理生理学与OAB联系起来的转化研究。 公共卫生相关性：膀胱过度活动症（OAB）是一种非常普遍的疾病，在美国影响超过1600万人。OAB的诊断和治疗仍处于初级阶段，几乎完全依赖于患者报告的症状。通过基础科学实验增加对这种情况的了解，我们希望了解OAB的原因。具体来说，我们将重点关注膀胱内衬细胞（尿路上皮CRIIS）在OAB病因中的作用。

DESCRIPTION (provided by applicant): The pathophysiology of OAB is unknown. While there are proposed etiologies including detrusor smooth muscle and neural mechanisms, the potential contribution of the bladder urothelial cells (BUC) to OAB is a new avenue of inquiry. The University of Maryland Interdisciplinary Research Center (UM-IRC) in benign urology will perform a planning study in which bladder urothelial biopsies will be obtained from subjects with no urinary incontinence and no voiding symptoms (controls) and from subjects with OAB symptoms (urge incontinence). Primary BUC cultures derived from these biopsies will be studied in the laboratories of the Program Director (Chai) and the two co-principal investigators (Birder, Keay). Because these labs already have independent funding, the multiple PI approach for the UM-IRC is utilized. The intent of the laboratory studies Is to obtain preliminary laboratory data which then can help statistically power the next OAB trial using laboratory objective measures as primary outcomes. The three phenotypes of BUC that will be measured are expression of intracellular polyamines, expression of tight junction proteins, and cellular mechanosensitivity measured by adenosine triphosphate (ATP) release in response to hypo-osmotic and chemical stimuli. Early preliminary data suggest alterations in all three of these phenotypes in OAB BUC. During this planning phase, the UM-IRC will firmly establish collaboration among the three laboratories which are already active in basic bladder urothelial biologic studies. An advisory panel will be used to govern the UM-IRC during the planning phase. Because the most important factor during the first two year is recruitment of OAB and control subjects to undergo bladder urothelial biopsies, the advisory panel will maintain constant surveillance of the recruitment numbers in addition to subject safety. The UM-IRC will utilize the Univ of Maryland Continence and Pelvic Center for recruitment. There are several OAB clinical trials currently ongoing which can help with the recruitment for this proposal. Based on the budgetary constraints of the RFA, 10 OAB and 10 control subjects will be enrolled. The UM-IRC will utilize an interdisciplinary approach in performing translational research linking urothelial pathophysiology to OAB. PUBLIC HEALTH RELEVANCE: Overactive bladder (OAB) is a highly prevalent condition affecting over 16 million people in the USA. Diagnosis and treatment for OAB remains rudimentary and rely almost exclusively on patient reported symptoms. By increasing the understanding of this condition with basic science experiments, we hope to understand the causes for OAB. Specifically we will focus on the role of the bladder lining cells (urothelial CRIIS) in the cause of OAB.