Univ of Maryland Baltimore Interdisciplinary Research Center in Benign Urology

马里兰大学巴尔的摩良性泌尿外科跨学科研究中心

• 批准号: 8151016
• 负责人: LORI A BIRDER
• 金额: $ 23.95万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8151016
• 关键词: Adenosine Triphosphate; Affect; Baltimore; Basic Science; Benign; Biopsy; Bladder; Bladder Control; Bladder Urothelial Cell; Cell Culture Techniques; Cell Line; Chemicals; Clinical Trials; Collaborations; Data; Diagnosis; Enrollment; Etiology; Functional disorder; Funding; Interdisciplinary Study; Laboratories; Laboratory Study; Link; Maryland; Measures; Overactive Bladder; Patients; Pelvis; Phase; Phenotype; Polyamines; Principal Investigator; Proteins; Reporting; Role; Safety; Smooth Muscle; Stimulus; Symptoms; Tight Junctions; Translational Research; Universities; Urge Incontinence; Urinary Incontinence; Urology; Urothelial Cell; base; interdisciplinary approach; neuromechanism; primary outcome; programs; public health relevance; research study; response

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.

描述（由申请人提供）：OAB的病理生理尚不清楚。虽然提出的病因在内，包括裂痕平滑肌和神经机制，但膀胱尿路上皮细胞（BUC）对OAB的潜在贡献是一种新的询问途径。马里兰州大学跨学科研究中心（UM-IRC）将在泌尿外科进行一项计划研究，其中将从没有尿失禁的受试者和没有缺失症状（对照组）的受试者和患有OAB症状（急切性无关）的受试者中获得膀胱尿路上皮活检。将在计划主任（CHAI）的实验室和两名联合主持研究人员（Birder，Keay）的实验室中研究源自这些活检的原发性BUC文化。由于这些实验室已经具有独立的资金，因此使用了UM-ir的多个PI方法。实验室研究的目的是获得初步的实验室数据，然后可以使用实验室客观措施作为主要结果来帮助统计上的OAB试验为下一个OAB试验提供动力。将测量的BUC的三种表型是细胞内聚胺的表达，紧密连接蛋白的表达以及通过三磷酸腺苷（ATP）释放测得的细胞机械敏感性，以响应低渗透性和化学刺激。早期初步数据表明OAB BUC中所有三种表型的改变。在这个计划阶段，UM-IRC将在已经活跃于基本膀胱尿皮上生物学研究的三个实验室之间建立合作。在计划阶段，咨询面板将用于管理UM-IRC。由于前两年中最重要的因素是招募OAB和控制受试者进行膀胱尿路上皮活检，因此除了受试者安全性外，该咨询小组还将保持对招募数字的持续监视。 UM-ir将利用马里兰州境内和骨盆招募中心进行招募。目前正在进行的几项OAB临床试验可以帮助该提案的招聘。根据RFA的预算限制，将招募10个OAB和10个控制对象。 UM-ir将利用跨学科的方法进行转化研究，将尿路上皮病理生理学与OAB联系起来。 公共卫生相关性：过度活跃的膀胱（OAB）是一种高度普遍的状况，影响了美国超过1600万人。 OAB的诊断和治疗仍然是基本的，几乎完全依赖于患者报告的症状。通过基础科学实验，通过提高对这种状况的理解，我们希望了解OAB的原因。具体而言，我们将重点关注膀胱内膜细胞（尿路上皮CRII）在OAB原因中的作用。