{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T02:42:01Z","timestamp":1773283321756,"version":"3.50.1"},"reference-count":25,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2013,1,28]],"date-time":"2013-01-28T00:00:00Z","timestamp":1359331200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Department of Medical Research, Kaohsiung Medical University Hospital","award":["KMUH-100-0R44"],"award-info":[{"award-number":["KMUH-100-0R44"]}]},{"DOI":"10.13039\/501100004694","name":"Kaohsiung Medical University","doi-asserted-by":"crossref","award":["KMU-Q098015"],"award-info":[{"award-number":["KMU-Q098015"]}],"id":[{"id":"10.13039\/501100004694","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Kaohsiung Municipal Hsiao-Kang Hospital","award":["KNHK-100-025"],"award-info":[{"award-number":["KNHK-100-025"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurourology and Urodynamics"],"published-print":{"date-parts":[[2013,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>The aims of the present study were to investigate voiding patterns, tissue constituents and the expressions of cyclooxygenase\u20102 (COX\u20102) and nitric oxide synthase (NOS) involved in ketamine\u2010induced ulcerative cystitis in rat urinary bladder.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Thirty<jats:italic>Sprague\u2013Dawley<\/jats:italic>rats were distributed into three groups which received saline or ketamine (25\u2009mg\/kg\/day) for a period of 14 and 28 days. In each group, cystometry was performed weekly and the concentration of ketamine and its metabolites (norketamine) was assayed. Paraffin\u2010embedded sections were stained with Masson's trichrome stain, and ketamine\u2010induced morphological changes were examined. Western blot analyses were carried out to examine the expressions of COX\u20102 and different NOS isoforms in bladder tissues. Immunofluorescence study was done to evaluate the expressions of COX\u20102 and macrophage infiltration (stained with ED\u20101 macrophage cell surface antigen) within the bladder.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Ketamine treatment resulted in bladder hyperactivity and the non\u2010voiding contractions were significantly increased. The urine concentrations of ketamine and norketamine were much higher in ketamine\u2010treated group. Moreover, ulcerated urothelium and mononuclear cell infiltration were noted in ketamine\u2010treated group. These alterations in urodynamic functions and tissue constituents were accompanied by increases in the expression of COX\u20102. Two NOS isoforms (iNOS and eNOS) were also overexpressed, but no significant change was observed for nNOS. COX\u20102 positive stained cells were significantly increased. Meanwhile, increased amounts of ED\u20101 positive stained macrophages were present and most of COX\u20102 expressed cells were co\u2010stained with ED\u20101 in the early stage of ketamine treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Ketamine treatment affected bladder tissues by enhancing interstitial fibrosis and accelerating macrophages infiltration. Ketamine also initiated the up\u2010regulations of COX\u20102 and iNOS and eNOS expressions. These up\u2010regulated enzymes might play an important role in contributing to ketamine\u2010induced alterations in micturition patterns and ulcerative cystitis.<jats:italic>Neurourol. Urodynam. 32:1137\u20131143, 2013<\/jats:italic>. \u00a9 2013 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/nau.22367","type":"journal-article","created":{"date-parts":[[2013,1,28]],"date-time":"2013-01-28T14:36:56Z","timestamp":1359383816000},"page":"1137-1143","source":"Crossref","is-referenced-by-count":68,"title":["Dual involvements of cyclooxygenase and nitric oxide synthase expressions in ketamine\u2010induced ulcerative cystitis in rat bladder"],"prefix":"10.1002","volume":"32","author":[{"given":"Shu\u2010Mien","family":"Chuang","sequence":"first","affiliation":[{"name":"Yuh\u2010Ing Junior College of Health Care and Management Kaohsiung Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keh\u2010Min","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anatomy, College of Medicine Kaohsiung Medical University Kaohsiung 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