NITRIC OXIDE IN UTIS AND INTERSTITIAL CYSTITIS

尿路感染和间质性膀胱炎是两种 主要影响泌尿系统的病理情况 妇女，她们有医疗、心理、社会和经济方面的 这意味着什么。这个提议的统一假设是，硝酸根 氧化物(NO)，一种小的亲脂气体分子，从 非肾上腺素能、非胆碱能神经元，在 多种哺乳动物组织，包括巨噬细胞和中性粒细胞 作为UTIS和IC的调解人。我们发现：1)尿液中的微粒 无症状女性的部分具有更高的一氧化氮合酶活性 在无症状男性中观察到；2)一氧化氮合酶(NOS)的亚型 尿路感染男性和女性尿小球活性增加 这种一氧化氮合酶具有类似于诱导型一氧化氮合酶亚型(INOS)的性质 这在巨噬细胞和中性粒细胞中已有描述；3)女性患者 患有IC的患者尿液颗粒分数中的NOS活性较低 与对照组或尿路感染患者相比；以及4)IC膀胱组织颗粒 一氧化氮合酶活性与尿液颗粒一氧化氮合酶活性相当 这一活动似乎是一种iNOS样活动。测试我们的 假设我们计划：1)确定尿粒中的细胞类型 含有诱导型一氧化氮合酶活性；2)分离并鉴定 尿小球中存在并增加的一氧化氮合酶的异构体 通过利用抗体或cdna探针；3)确定 一氧化氮合酶参与尿路感染或IS的病理方面的诱导 对尿路感染的部分修复性反应；4)决定 诱导型一氧化氮合酶诱导剂对体外培养细胞一氧化氮合酶水平的影响 尿路感染时程的作用；5)确定一氧化氮合酶是否增加 诱导型一氧化氮合酶激活剂的活性在炎症方面有所不同 从男性和女性尿液中分离的细胞；6)特性-纳米 正常和IC膀胱标本的收缩-松弛现象 患者；7)评估尿中一氧化氮合酶活性、功能和同工酶类型(S 以及IC患者和对照组的膀胱活检，并评估一氧化氮合酶 IC患者的活动作为治疗反应的函数。 所获得的数据可能为治疗方法的发展提供理论基础 对于这些病理状态。

Urinary tract infections (UTIs) and interstitial cystitis (IC) are two pathologic conditions of the urinary system which predominately affect women and which have medical, psychological, sociological and economic implications. The unifying hypothesis of this proposal is that nitric oxide (NO), a small lipophilic gaseous molecule, which is released from non-adrenergic, noncholinergic neurons and which is synthesized in a variety of mammalian tissues including macrophages and neutrophils, acts as a mediator in UTIs and IC. We have shown that: 1) urine particulate fractions from asymptomatic women has greater NOS activity than that observed in asymptomatic men; 2) an isoform of NO synthase (NOS) has increased activity in urine pellets of men and women with UTIs and that this NOS has properties similar to that of an inducible NOS isoform (iNOS) that has been described in macrophages and neutrophils; 3) female patients with IC have less NOS activity in their urine pellet particulate fraction than do controls or patients with UTIs; and 4) IC bladder tissue pellet NOS activity is comparable to IC urine pellet particulate NOS activity and that this activity appears to be an iNOS-like activity. To test our hypothesis we plan to: 1) determine the cell type in the urine pellet which contains the iNOS-like activity; 2) isolate and characterize the isoform of NOS that is present in the urine pellet and which is increased during UTI by utilizing antibodies or cDNA probes; 3) determine whether NOS is involved in the induction of the pathologic aspects of UTIs or is a part of the reparative response to the UTI; 4) determine the effect of inducers of iNOS on NOS levels in cultured cells isolated from urine as a function of the time course of the UTI; 5) determine if increases in NOS activity in response to agents that activate iNOS differ in inflammatory cells isolated from urine of men and women; 6) characterize -NANC contraction-relaxation phenomena in bladder specimens from normal and IC patients; 7) assess NOS activity, function and isoenzyme type(s) in urine and bladder biopsies of IC patients and controls and 8) assess NOS activity as a function of the response to treatment in patients with IC. The data obtained may provide a rationale for the development of therapies for these pathologic states.