CAMP STIMULATED SWEAT RATE IN CYSTIC FIBROSIS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。该项目的目标是开发一种环AMP（cAMP）刺激的“出汗率”测试，该测试将区分囊性纤维化跨膜传导调节器（CFTR）的完全功能，部分功能和非功能形式。胆碱能和肾上腺素能激动剂都能刺激汗液产生.胆碱能刺激汗液的收集和随后汗液氯化物浓度的测量是囊性纤维化（CF）的标准诊断测试-毛果芸香碱离子电渗汗液测试的基础。用毛果芸香碱刺激汗液产生导致汗腺中等渗分泌物的初始产生。在非CF患者中，当分泌物穿过汗管时，氯化物被重吸收，导致汗液中的氯化物浓度较低，因为它出现在皮肤上。这种氯离子再吸收依赖于功能性CFTR的存在。在缺乏功能性CFTR的CF患者中，汗液氯化物浓度仍然很高，这是大多数（但不是全部）CF患者与非CF患者的区别。然而，该技术不能区分CFTR突变的杂合子携带者和非携带者，汗液氯离子浓度也与疾病严重程度无关。 假设cAMP介导的出汗率的测量将区分CF受试者、非CF受试者和未受影响的CFTR突变携带者。次要假设是CFTR活性和出汗率之间存在相关性，使得未受影响的CFTR突变携带者将具有CF和非CF对照受试者的中间出汗率。另一个次要假设是，不同类别的CFTR突变可能与不同水平的出汗率相关。 所有性别和年龄的受试者都有资格参加。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The goal of this project is the development of a cyclic-AMP(cAMP)-stimulated "sweat rate" test that will discriminate between fully functional, partially functional, and non-functional forms of the Cystic Fibrosis Transmembrane Conductance Regulator(CFTR). Sweat production can be stimulated by both cholinergic amp; adrenergic agonists. Collection of cholinergic stimulated sweat amp; the subsequent measurement of sweat chloride concentration is the basis of a standard diagnostic test for cystic fibrosis (CF), the pilocarpine iontophoresis sweat test. Stimulation of sweat production with pilocarpine leads to initial production of an isotonic secretion in the sweat gland. In non-CF patients, as the secretion traverses the sweat duct, chloride is reabsorbed leading to low concentrations of chloride in sweat as it appears on the skin. This chloride resorption is dependent on the presence of functional CFTR. In CF patients, who lack functional CFTR, the sweat chloride concentration remains high, amp; distinguishes most, but not all, CF from non-CF patients. However, this technique does not distinguish heterozygote carriers of CFTR mutations from non-carriers, nor does the sweat chloride concentration correlate with disease severity. The hypothesis is that measurement of cAMP-mediated sweat rates will distinguish among CF subjects, non-CF subjects, and non-affected carriers of CFTR mutations. A secondary hypothesis is that there will be a correlation between CFTR activity and sweat rate such that non-affected carriers of CFTR mutations will have intermediate sweat rates to CF and non-CF control subjects. Another secondary hypothesis is that different classes of CFTR mutations can be associated with different levels of sweat rate. Subjects of both genders and all ages are eligible for entry.