{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T02:51:54Z","timestamp":1781751114008,"version":"3.54.5"},"reference-count":31,"publisher":"Wiley","issue":"S1","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":46,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DK135076\u201001"],"award-info":[{"award-number":["R01 DK135076\u201001"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL109002"],"award-info":[{"award-number":["R01 HL109002"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000873","name":"Andrew W. Mellon Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000873","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Urology"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Bladder pain and associated lower urinary tract symptoms (LUTSs) are hallmark features of interstitial cystitis\/bladder pain syndrome (IC\/BPS) and hemorrhagic cystitis (HC). IC\/BPS is characterized by bladder\u2010based pain and irritative bladder symptoms, with or without gross inflammatory changes (Hunner lesions) in the bladder wall, and the absence of well\u2010described causes such as infection or neoplastic disease. The clinical features of HC are similar to IC\/BPS, but in this instance, they are always associated with visible inflammatory disease with known etiologies such as infection or a complication of radiation and\/or chemotherapy. While progress has been made in defining the spinal circuits that gate pain signals emanating from the pelvic viscera, lack of a clear understanding of the mechanisms leading to cystitis\u2010induced visceral pain and lack of validated therapeutic targets for cystitis are a source of frustration for clinicians treating conditions such as IC\/BPS and HC and their patients. This review will focus on an emerging therapy for cystitis, namely 8\u2010aminoguanine (8\u2010AG), which inhibits the enzyme purine nucleoside phosphorylase (PNPase). PNPase is important for metabolism of \u201ctissue\u2010protective\u201d purine metabolites into \u201ctissue\u2010damaging\u201d purines that generate free radicals. IC\/BPS patients without and with Hunner lesions exhibit a dysregulation of purine metabolism, with elevated levels of urotoxic purine metabolites compared to healthy controls. Rodents treated with cyclophosphamide are a standard animal model for cystitis and exhibit multiple abnormalities, including increased urinary frequency, neural mechanosensitivity, suppression of pain\u2010reducing purines, and increased urothelial inflammation\/damage. Orally administered 8\u2010AG prevents all observed histological, structural, biochemical, and physiological abnormalities in cyclophosphamide\u2010induced cystitis. These findings demonstrate that 8\u2010AG holds promise for reducing pain and preventing bladder damage for patients with cystitis\u2010associated pain and LUTS.<\/jats:p>","DOI":"10.1111\/iju.70418","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T01:19:17Z","timestamp":1781659157000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Rationale for the Use of 8\u2010Aminoguanine for the Management of Cystitis"],"prefix":"10.1111","volume":"33","author":[{"given":"Lori A.","family":"Birder","sequence":"first","affiliation":[{"name":"Renal\u2010Electrolyte Division, Department of Medicine University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"},{"name":"Department of Pharmacology and Chemical Biology University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel N. H.","family":"Stern","sequence":"additional","affiliation":[{"name":"Arthur Smith Institute for Urology, Northwell Health Zucker School of Medicine at Hofstra\/Northwell  Lake Success New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Moldwin","sequence":"additional","affiliation":[{"name":"Arthur Smith Institute for Urology, Northwell Health Zucker School of Medicine at Hofstra\/Northwell  Lake Success New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin K.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Chemical Biology University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"Campbell\u2010Walsh Urology","author":"Hanno P. 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