{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T16:21:26Z","timestamp":1780676486929,"version":"3.54.1"},"reference-count":28,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T00:00:00Z","timestamp":1594944000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Urology"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine whether patients with interstitial cystitis have elevated levels of toxic urinary cations, to identify and quantify these cationic metabolites, and to assess their cytotoxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Isolation of cationic fraction was achieved by solid phase extraction using an Oasis MCX cartridge on urine specimens from interstitial cystitis patients and controls. C<jats:sub>18<\/jats:sub> reverse phase high\u2010performance liquid chromatography was used to profile cationic metabolites, and they were quantified by the area under the peaks and normalized to creatinine. Major cationic fraction peaks were identified by reverse phase high\u2010performance liquid chromatography and liquid chromatography\u2013mass spectrometry. HTB\u20104 urothelial cells were used to determine the cytotoxicity of cationic fraction and of individual metabolites.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The reverse phase high\u2010performance liquid chromatography analysis was carried out on cationic fraction metabolites isolated from urine samples of 70 interstitial cystitis patients and 34 controls. The mean for controls versus patients was 3.84 (standard error of the mean 0.20) versus 6.71 (0.37) mAU*min\/\u00b5g creatinine, respectively (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0001). The cationic fraction cytotoxicity normalized to creatinine for controls versus patients in mean percentage was \u22127.79% (standard error of the mean 3.32%) versus 20.03% (standard error of the mean 2.75%; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0005). The major toxic cations were 1\u2010methyladenosine, 1\u2010methylguanine, N<jats:sup>2<\/jats:sup>,N<jats:sup>2<\/jats:sup>\u2010dimethylguanosine and L\u2010tryptophan.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These data confirm significant elevation of toxic cations in the urine of interstitial cystitis patients. These toxic cations likely represent a primary cause of interstitial cystitis, as they can injure the bladder mucus and initiate an epithelial leak.<\/jats:p><\/jats:sec>","DOI":"10.1111\/iju.14293","type":"journal-article","created":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T07:27:07Z","timestamp":1594970827000},"page":"731-735","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Role of urinary cations in the etiology of interstitial cystitis: A multisite study"],"prefix":"10.1111","volume":"27","author":[{"given":"C Lowell","family":"Parsons","sequence":"first","affiliation":[{"name":"Department of Urology University of California San Diego La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sulabha","family":"Argade","sequence":"additional","affiliation":[{"name":"Department of Urology University of California San Diego La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J","family":"Evans","sequence":"additional","affiliation":[{"name":"Department of Urology Wake Forest Baptist Medical Center Winston\u2010Salem North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Proctor","sequence":"additional","affiliation":[{"name":"Georgia Urology Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J Curtis","family":"Nickel","sequence":"additional","affiliation":[{"name":"School of Medicine Queen\u2019s University Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt T","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"Mid\u2010Michigan Health Centers Jackson Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip C","family":"Bosch","sequence":"additional","affiliation":[{"name":"Department of Urology University of California San Diego La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1464-410X.2010.09843.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(17)39897-X"},{"key":"e_1_2_7_4_1","first-page":"493","article-title":"Bladder surface glycosaminoglycans is a human epithelial permeability barrier","volume":"171","author":"Lilly JD","year":"1990","journal-title":"Surg. 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