{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T21:46:22Z","timestamp":1775079982651,"version":"3.50.1"},"reference-count":24,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T00:00:00Z","timestamp":1731456000000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["LUTS"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>The study was aimed to establish the \u201cinside\u2010out\u201d preparation with the urothelium and investigate the changes in urothelial permeability of the cyclophosphamide (CYP)\u2010induced cystitis model in rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In female rats with or without CYP injection, the isolated whole bladder was utilized as an \u201cinside\u2010out\u201d preparation with the urothelium, which was created by reversing the bladder from a top portion. The preparation was fixed in the organ bath, and instilled with a Krebs solution (0.5\u2009mL) through the bladder neck. After it was kept under an isovolumetric condition, high K<jats:sup>+<\/jats:sup> (KCl: 50\u2009mM) or acetylcholine (ACh: 10\u2009\u03bcM) was added into the organ bath.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the normal bladder, the intravesical pressure of the inside\u2010out preparation with the urothelium did not change with the addition of KCl or ACh. Contrarily, in the CYP\u2010injected bladder 24 or 48\u2009h after injection of CYP, the intravesical pressure of the inside\u2010out preparation increased with the addition of KCl or ACh. Histological examinations showed a denuded and\/or cracked surface of the urothelial layer, and the intensity of uroplakin III staining of the urothelial layer decreased in the CYP\u2010injected rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The study demonstrated the bladder urothelium has robust barrier mechanisms for preventing the absorption of water (urine) under the normal condition. However, these barrier mechanisms were disrupted in the CYP\u2010induced cystitis, suggesting that water and urine insults can be permeabilized into the urinary bladder, specifically to the smooth muscle layer.<\/jats:p><\/jats:sec>","DOI":"10.1111\/luts.12538","type":"journal-article","created":{"date-parts":[[2024,11,14]],"date-time":"2024-11-14T00:23:58Z","timestamp":1731543838000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Changes of the Urothelial Barrier System in the Cyclophosphamide\u2010Induced Cystitis in Rats by Using a Newly Established \u201cInside\u2010Out\u201d Urinary Bladder Preparation"],"prefix":"10.1111","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4645-9293","authenticated-orcid":false,"given":"Naoki","family":"Aizawa","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology Dokkyo Medical University School of Medicine  Tochigi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroki","family":"Natsuya","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Dokkyo Medical University School of Medicine  Tochigi Japan"},{"name":"Department of Urology Fukushima Medical University School of Medicine  Fukushima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoe","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Dokkyo Medical University School of Medicine  Tochigi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,11,13]]},"reference":[{"issue":"891","key":"e_1_2_8_2_1","first-page":"23","article-title":"The Ultrastructure and Chemistry of the Luminal Plasma Membrane of the Mammalian Urinary Bladder: A Structure With Low Permeability to Water and Ions","volume":"268","author":"Hicks R. 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