CAMP STIMULATED SWEAT RATE IN CYSTIC FIBROSIS

该项目的目标是开发一种循环amp （cAMP）刺激的“汗率”测试，该测试将区分完全功能、部分功能和非功能形式的囊性纤维化跨膜电导调节剂（CFTR）。胆碱能和肾上腺素能激动剂都能刺激出汗。收集胆碱能刺激汗液及随后测量汗液中胆碱浓度是囊性纤维化（CF）的标准诊断试验——匹罗卡品离子导入汗液试验的基础。用匹罗卡品刺激汗液产生可导致汗腺初始产生等渗分泌。在非cf患者中，当分泌物穿过汗管时，氯化物被重新吸收，导致汗液中的氯化物浓度较低，因为它出现在皮肤上。这种氯化物的吸收依赖于功能性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CF患者与非CF患者的区别，但不是全部。然而，该技术不能区分CFTR突变的杂合子携带者和非携带者，汗液氯化物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.