title: Abnormal Sensory Protein Expression and Urothelial Dysfunction in Ketamine-Related Cystitis in Humans.
abstract: OBJECTIVE
  The aim of this study was to analyze patterns of sensory protein expression and urothelial dysfunction in ketamine-related cystitis (KC) in humans.
  
  
  METHODS
  Biopsies of bladder mucosa were performed in 29 KC patients during cystoscopy. Then specimens were analyzed for tryptase, zonula occludens-1 (ZO-1), E-cadherin, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) with immunofluorescence staining and quantification. In addition, 10 healthy control bladder specimens were analyzed and compared with the KC specimens. Another 16 whole bladder specimens obtained from partial cystectomy were also analyzed for the muscarinic receptors M2 and M3, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), β-3 adrenergic receptors (β3-ARs), and the P2X3receptor by western blotting. In addition, 3 normal control bladder specimens were analyzed and compared with the KC specimens.
  
  
  RESULTS
  The KC bladder mucosa revealed significantly less expression of ZO-1 and E-cadherin, and greater expression of TUNEL and tryptase activity than the control samples. The expression of M3 and β3-AR in the KC specimens was significantly greater than in the controls. The expression of iNOS, eNOS, M2, and P2X3was not significantly different between the KC and control specimens.
  
  
  CONCLUSIONS
  The bladder tissue of KC patients revealed significant urothelial dysfunction, which was associated with mast-cell mediated inflammation, increased urothelial cell apoptosis, and increased expression of the M3 and β3-AR.
authors.affiliation: Division of Urology, Department of Surgery, Taipei Tzu Chi General Hospital, Buddhist Tzu Chi Medical Foundation, Taipei, Taiwan.|Department of Urology, School of Medicine, Tzu Chi University, Hualien, Taiwan.
authors.forename: Yao Chou
authors.identifier: 0000-0002-2833-5609
authors.initials: YC
authors.lastname: Tsai
authors.affiliation: Department of Medicine and Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Lori
authors.identifier: 0000-0002-3393-2256
authors.initials: L
authors.lastname: Birder
authors.affiliation: Department of Urology, School of Medicine, Tzu Chi University, Hualien, Taiwan.|Department of Urology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan.
authors.forename: Hann-Chorng
authors.identifier: 0000-0001-7165-4771
authors.initials: HC
authors.lastname: Kuo
keywords: Ketamine; Urothelium