CAMP STIMULATED SWEAT RATE IN CYSTIC FIBROSIS

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。 汗液的产生可以通过胆碱能和肾上腺素能激动剂来刺激。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，并且将大多数但不是全部的CF与非CF患者区分开来。 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。

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 & adrenergic agonists. Collection of cholinergic stimulated sweat & the subsequent measurement of sweat cholride 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, & 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.