INDUCIBLE NITRIC OXIDE SYNTHASE IN THE BLADDER OF SPINAL CORD INJURED PATIENTS WITH A CHRONIC INDWELLING URINARY CATHETER

一氧化氮合酶 医学 一氧化氮 病理 膀胱 脊髓损伤 泌尿系统 脊髓 泌尿科 内科学 精神科
作者
Barry M. Wall,Roger R. Dmochowski,Mark J. Malecha,Therese A. Mangold,Mary Cooke
出处
期刊:The Journal of Urology [Lippincott Williams & Wilkins]
卷期号:165 (5): 1457-1461 被引量:26
标识
DOI:10.1016/s0022-5347(05)66327-6
摘要

No AccessJournal of UrologyCLINICAL UROLOGY: Original Articles1 May 2001INDUCIBLE NITRIC OXIDE SYNTHASE IN THE BLADDER OF SPINAL CORD INJURED PATIENTS WITH A CHRONIC INDWELLING URINARY CATHETER BARRY M. WALL, ROGER R. DMOCHOWSKI, MARK MALECHA, THERESE MANGOLD, and MARY A. BOBAL C. ROBERT COOKE BARRY M. WALLBARRY M. WALL More articles by this author , ROGER R. DMOCHOWSKIROGER R. DMOCHOWSKI More articles by this author , MARK MALECHAMARK MALECHA More articles by this author , THERESE MANGOLDTHERESE MANGOLD More articles by this author , and MARY A. BOBAL C. ROBERT COOKEMARY A. BOBAL C. ROBERT COOKE More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(05)66327-6AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: Spinal cord injured patients are at increased risk for bladder carcinoma. Nitric oxide production in areas of chronic inflammation may provide a stimulus for carcinogenesis by serving as a source of nitrosating agents that generate potentially carcinogenic nitrosamines from secondary amines normally present in urine. Materials and Methods: To determine whether inducible nitric oxide synthase is expressed as a catalyst for sustained nitric oxide production by cellular elements in chronically inflamed bladder mucosa immunohistochemical studies were performed on mucosal biopsies obtained from 37 adults with spinal cord injury. All participants had required a chronic indwelling urethral or suprapubic catheter for greater than 8 years. Results: Histopathological studies revealed active inflammatory infiltrates in all 37 biopsy specimens, squamous metaplasia in 20, epithelial dysplasia in 3 and carcinoma in 1. Inducible nitric oxide synthase was detected in inflammatory cells localized to the lamina propria. Inducible nitric oxide synthase positive cells were identified as macrophages using monoclonal antibodies to macrophage antigen. There was no inducible nitric oxide synthase expression in the urothelial cell layers. Immunostaining for inducible nitric oxide synthase was not detected in bladder mucosal biopsy specimens obtained from cadaveric organ donors. Conclusions: Inducible nitric oxide synthase is expressed in inflammatory macrophages in areas of chronic inflammation in the bladder mucosa of spinal cord injured patients with a chronic indwelling bladder catheter. The expression of inducible nitric oxide synthase may potentially lead to the sustained production of nitric oxide and its oxidative products, the nitrosation of urinary amines and the formation of potentially carcinogenic nitrosamines in the bladder. References 1 : The incidence of bladder cancer in paraplegia. Paraplegia1966; 4: 85. Google Scholar 2 : Bladder cancer risk in patients with spinal cord injury. J Spinal Cord Med1998; 21: 230. Google Scholar 3 : Risk factors for bladder tumors in spinal cord injury patients. J Urol1996; 155: 1248. Link, Google Scholar 4 : Inducible nitric oxide synthase in human diseases. Clin Exp Immunol1998; 113: 147. Google Scholar 5 : Chronic infections and inflammatory processes as cancer risk factors: possible role of nitric oxide in carcinogenesis. Mutat Res1994; 305: 253. Google Scholar 6 : Role of N-nitroso compounds (NOC) and N-nitrosation in etiology of gastric, esophageal, nasopharyngeal and bladder cancer and contribution to cancer of known exposures to NOC. Cancer Lett1995; 93: 17. Google Scholar 7 : Expression of nitric oxide synthase in the human nasal mucosa. Am J Respir Crit Care Med1996; 153: 847. Google Scholar 8 : Genital and urinary tract diseases and bladder cancer. Cancer Res1991; 51: 629. Google Scholar 9 : Potential genotoxicity of chronically elevated nitric oxide: a review. Mutat Res1995; 339: 73. Google Scholar 10 : Macrophage synthesis of nitrite, nitrate, and N-nitrosamines: precursors and role of the respiratory burst. Proc Natl Acad Sci USA1987; 84: 6369. Google Scholar 11 : Bacterial infection induces nitric oxide synthase in human neutrophils. J Clin Invest1997; 99: 110. Google Scholar 12 : Nitrosamine formation by denitrifying and non-denitrifying bacteria: implication of nitrite reductase and nitrate reductase in nitrosation catalysis. J Gen Microbiol1988; 134: 221. Google Scholar 13 : N-nitrosamine generation by urinary tract infections in spine injured patients. Paraplegia1992; 30: 855. Google Scholar 14 : Denitrification: production and consumption of nitric oxide. Appl Environ Microbiol1994; 60: 1053. Google Scholar 15 : Nitrotyrosine as biomarker for reactive nitrogen species. Methods Enzymol1996; 269: 175. Google Scholar 16 : Rat, mouse and human neutrophils stimulated by a variety of activating agents produce much less nitrite than rodent macrophages. Immunology1995; 84: 135. Google Scholar 17 : Bladder histological changes associated with chronic indwelling urinary catheter. J Urol1999; 161: 1106. Link, Google Scholar 18 : Persistence of carcinogen-altered cell population in rat urothelium which can be promoted to tumors by chronic inflammatory stimulus. Cancer Res1994; 54: 2630. Google Scholar 19 : Nitrate, nitrite and volatile N-nitroso compounds in the urine of Schistosoma haematobium and Schistosoma mansoni infected patients. Carcinogenesis1994; 15: 619. Google Scholar 20 : DNA damage and mutation in human cells exposed to nitric oxide in vitro. Proc Natl Acad Sci USA1992; 89: 3030. Google Scholar From the Division of Nephrology, Department of Medicine, Division of Urology, Departments of Surgery and Pathology, Veterans Affairs Medical Center, Memphis, Tennessee© 2001 by American Urological Association, Inc.FiguresReferencesRelatedDetailsCited byJOHANSSON R, POLJAKOVIC M, ANDERSSON K and PERSSON K (2018) Expression of Nitric Oxide Synthase in Bladder Smooth Muscle Cells: Regulation by Cytokines and L-ArginineJournal of Urology, VOL. 168, NO. 5, (2280-2285), Online publication date: 1-Nov-2002. Volume 165Issue 5May 2001Page: 1457-1461 Advertisement Copyright & Permissions© 2001 by American Urological Association, Inc.Keywordsurinary catheterizationspinal cord injuriesbladdernitric-oxide synthaseMetricsAuthor Information BARRY M. WALL More articles by this author ROGER R. DMOCHOWSKI More articles by this author MARK MALECHA More articles by this author THERESE MANGOLD More articles by this author MARY A. BOBAL C. ROBERT COOKE More articles by this author Expand All Advertisement PDF downloadLoading ...

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