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 的病理生理学尚不清楚。虽然提出的病因包括逼尿肌平滑肌和神经机制，但膀胱尿路上皮细胞 (BUC) 对 OAB 的潜在贡献是一个新的研究途径。马里兰大学良性泌尿学跨学科研究中心 (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）的受试者中获取膀胱尿路上皮活检。来自这些活检的原代 BUC 培养物将在项目主任 (Chai) 和两位联合首席研究员 (Birder、Keay) 的实验室中进行研究。由于这些实验室已经拥有独立的资金，因此采用了 UM-IRC 的多 PI 方法。实验室研究的目的是获得初步实验室数据，然后使用实验室客观指标作为主要结果，为下一次 OAB 试验提供统计支持。将测量的 BUC 的三种表型是细胞内多胺的表达、紧密连接蛋白的表达以及通过响应低渗和化学刺激而释放的三磷酸腺苷 (ATP) 测量的细胞机械敏感性。早期初步数据表明 OAB BUC 中所有这三种表型均发生改变。在此规划阶段，UM-IRC 将在已经活跃于基本膀胱尿路上皮生物学研究的三个实验室之间牢固地建立合作。在规划阶段，将由一个顾问小组来管理 UM-IRC。由于前两年最重要的因素是招募 OAB 和对照受试者进行膀胱尿路上皮活检，因此除了受试者安全之外，顾问小组还将持续监测招募人数。 UM-IRC 将利用马里兰大学节制和骨盆中心进行招募。目前正在进行多项 OAB 临床试验，可以帮助该提案的招募。根据 RFA 的预算限制，将招募 10 名 OAB 和 10 名对照受试者。 UM-IRC 将利用跨学科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。 公共健康相关性：膀胱过度活动症 (OAB) 是一种非常普遍的疾病，影响着美国超过 1600 万人。 OAB 的诊断和治疗仍然处于初级阶段，几乎完全依赖于患者报告的症状。通过基础科学实验加深对这种情况的了解，我们希望了解 OAB 的原因。具体来说，我们将重点关注膀胱内膜细胞（尿路上皮 CRIIS）在 OAB 病因中的作用。