{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:18:09Z","timestamp":1791271089062,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2014,4,16]],"date-time":"2014-04-16T00:00:00Z","timestamp":1397606400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bjui-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJU International"],"published-print":{"date-parts":[[2014,8]]},"abstract":"\n Objectives<\/jats:title>\n \n To identify and characterise urinary cationic metabolites, defined as toxic factors, in patients with interstitial cystitis (\n IC<\/jats:styled-content>\n ) and in control subjects. To evaluate the cytotoxicity of the urinary cationic metabolite fraction of patients with\n IC<\/jats:styled-content>\n vs control subjects and of individual metabolites in cultured urothelial cells.\n <\/jats:p>\n <\/jats:sec>\n \n Subjects and Methods<\/jats:title>\n \n Cationic fractions (\n CFs<\/jats:styled-content>\n ) were isolated from the urine specimens of 62 patients with\n IC<\/jats:styled-content>\n and 33 control subjects by solid\u2010phase extraction.\n CF<\/jats:styled-content>\n metabolites were profiled using\n C<\/jats:styled-content>\n 18<\/jats:sub>\n reverse\u2010phase high performance liquid chromatography (\n RP\u2010HPLC<\/jats:styled-content>\n ) with\n UV<\/jats:styled-content>\n detection, quantified by area\u2010under\u2010the\u2010peaks using known standards, and normalized to creatinine.\n RP\u2010HPLC<\/jats:styled-content>\n and liquid chromatography (\n LC<\/jats:styled-content>\n )\u2010mass spectrometry (\n MS<\/jats:styled-content>\n )\/tandem\n MS<\/jats:styled-content>\n (\n MS<\/jats:styled-content>\n \/\n MS<\/jats:styled-content>\n ) were used to identify major\n CF<\/jats:styled-content>\n peaks.\n HTB<\/jats:styled-content>\n \u20104 urothelial cells were used to determine the cytotoxicity of\n CFs<\/jats:styled-content>\n and of individual metabolites with and without\n T<\/jats:styled-content>\n amm\u2013\n H<\/jats:styled-content>\n orsfall protein (\n THP<\/jats:styled-content>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n RP\u2010HPLC<\/jats:styled-content>\n analysis showed that metabolite quantity was twofold higher in patients with\n IC<\/jats:styled-content>\n compared with control subjects. The mean (\n sem<\/jats:sc>\n ) for control subjects vs patients was 3.1 (0.2) vs 6.3 (0.5) mAU*min\/\u03bcg creatinine (\n P<\/jats:italic>\n < 0.001).\n LC\u2010MS<\/jats:styled-content>\n identified 20 metabolites. Patients with\n IC<\/jats:styled-content>\n had higher levels of modified nucleosides, amino acids and tryptophan derivatives compared with control subjects. The\n CF<\/jats:styled-content>\n cytotoxicity was higher for patients with\n IC<\/jats:styled-content>\n compared with control subjects. The mean (\n sem<\/jats:sc>\n ) for control subjects vs patients was \u22122.3 (2.0)% vs 36.7 (2.7)% (\n P<\/jats:italic>\n < 0.001). A total of 17 individual metabolites were tested for their cytotoxicity. Cytotoxicity data for major metabolites were all significant (\n P<\/jats:italic>\n < 0.001): 1\u2010methyladenosine (51%), 5\u2010methylcytidine (36%), 1\u2010methyl guanine (31%),\n N<\/jats:styled-content>\n 4<\/jats:sup>\n \u2010acetylcytidine (24%),\n N<\/jats:styled-content>\n 7<\/jats:sup>\n \u2010methylguanosine (20%) and\n L<\/jats:styled-content>\n \u2010\n T<\/jats:styled-content>\n ryptophan (16%). These metabolites were responsible for higher toxicity in patients with\n IC<\/jats:styled-content>\n . The toxicity of all metabolites was significantly lower in the presence of control\n THP<\/jats:styled-content>\n (\n P<\/jats:italic>\n < 0.001).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Major urinary cationic metabolites were characterised and found to be present in higher amounts in patients with\n IC<\/jats:styled-content>\n compared with control subjects. The cytotoxicity of cationic metabolites in patients with\n IC<\/jats:styled-content>\n was significantly higher than in control subjects, and control\n THP<\/jats:styled-content>\n effectively lowered the cytotoxicity of these metabolites. These data provide new insights into toxic factor composition as well as a framework in which to develop new therapeutic strategies to sequester their harmful activity, which may help relieve the bladder symptoms associated with\n IC<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/bju.12603","type":"journal-article","created":{"date-parts":[[2013,12,10]],"date-time":"2013-12-10T08:06:40Z","timestamp":1386662800000},"page":"286-293","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Role of urinary cations in the aetiology of bladder symptoms and interstitial cystitis"],"prefix":"10.1111","volume":"114","author":[{"given":"C. Lowell","family":"Parsons","sequence":"first","affiliation":[{"name":"Department of Urology University of California (UC) San Diego Health System San Diego USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Shaw","sequence":"additional","affiliation":[{"name":"Department of Urology University of California (UC) San Diego Health System San Diego USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoltan","family":"Berecz","sequence":"additional","affiliation":[{"name":"Department of Urology University of California (UC) San Diego Health System San Diego USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongxuan","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry UC San Diego La Jolla CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Zupkas","sequence":"additional","affiliation":[{"name":"Department of Urology University of 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