MOLECULAR BASIS OF IDIOPATHIC DRY MOUTH

此申请是为一个程序项目的分子基础上的重点 治疗特发性口干口腔干燥症或口干的临床实体 大约有300万美国人受到影响，导致各种症状， 潜在高发病率的后果。唾液腺功能损害 包括口腔干燥感、言语困难、咀嚼困难 和吞咽，增加对口腔微生物疾病的易感性， 龋齿和真菌感染，以及牙齿矿物质的保护减少。 唾液功能减退的既定原因是药物的副作用， 放射治疗或自身免疫性疾病对唾液腺组织的损伤 如干燥综合征。然而，有一部分口干患者 包括约20%的没有明显病因的所有口干患者， 因此，这些患者被诊断为“特发性干细胞性白血病”。 嘴”。唾液流客观参数的存在与否 允许进一步细分特发性口干患者。以来 特发性口干的潜在机制尚未确定， 迄今可用的治疗方法充其量只是治标不治本。的 本建议中概述的研究旨在获得基础知识， 分子水平的外分泌生物学。要生成的数据 拟议的研究的最终目标是为以下方面开辟新的途径： 治疗应用。本计划项目的总体目标是 确定导致特发性口干的机制。那里 是3个子项目，旨在测试独立但相互关联的假设， 唾液腺功能障碍

This application is for a Program Project focusing on the molecular basis for idiopathic dry mouth. The clinical entity of xerostomia or dry mouth afflicts about 3 million Americans leading to a variety of symptoms and consequences of potentially high morbidity. The impairment of salivary function comprises the sensation of oral dryness, difficulties in speech, mastication and deglutition, increased susceptibilities to oral microbial diseases such as caries and fungal infections, and reduced protection of tooth mineral. Well established causes for salivary hypofunction are side effects of medications, damage to salivary gland tissue by radiation therapy or autoimmune diseases such as Sjogren's syndrome. There is, however, a subset of xerostomic patients comprising about 20% of all dry mouth patients for whom no obvious etiology can be ascertained and these patients are therefore diagnosed with "idiopathic dry mouth". The presence or absence of objective parameters for salivary flow allows a further subdivision of idiopathic dry mouth patients. Since the underlying mechanisms for idiopathic dry mouth have not been established the therapeutic approaches available so far are only palliative at best. The studies outlined in this proposal are designed to gain fundamental knowledge at the molecular level in this area of exocrine biology. The data to be generated by the proposed studies have the ultimate goal to open new avenues for therapeutic applications. The overall aims of this Program Project is to determine the mechanisms responsible for idiopathic forms of dry mouth. There are 3 subprojects aimed at testing separate but interrelated hypotheses of salivary dysfunction.