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BJU Int. 2013 Dec;112(8):1156-62. doi: 10.1111/bju.12256. Epub 2013 Aug 13.

Increased apoptosis and suburothelial inflammation in patients with ketamine-related cystitis: a comparison with non-ulcerative interstitial cystitis and controls.

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Department of Urology, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan.



To investigate the suburothelial inflammation and urothelial dysfunction that occurs with ketamine-related cystitis (KC) and interstitial cystitis/bladder pain syndrome (IC/BPS).


Bladder tissues from 16 patients with KC, 17 patients with IC/BPS and 10 control subjects were analysed. Immunofluorescence staining of the junction protein E-cadherin was carried out, and tryptase levels and a TUNEL assay were used to assess mast-cell activation and urothelial apoptosis, respectively. The fluorescence intensity of E-cadherin was measured using the ImageJ method. The percentages of activated mast cells and apoptotic cells were calculated as positive cells per unit area (4 μm(2) ).


The mean (sd) ages of the patients in the KC, IC/BPS and control groups were 25.0 (3.8), 41.3 (13.7) and 50.5 (9.6) years, respectively (P < 0.05). The mean (sd) distributions of E-cadherin in KC (10.1 [11.2]) and IC/BPS (25.1 [16.3]) tissues were significantly lower than in the control tissues (42.4 [16.7]; both P < 0.05). The mean (sd) number of activated mast cells, measured by tryptase signals in the KC (6.5 [3.7]) and IC/BPS (4.6 [3.0]) tissues, were significantly higher than in the control tissues (1.3 [1.12]; both P < 0.05). TUNEL staining showed a significantly higher mean (sd) number of apoptotic cells in KC (4.4 [2.5]) and IC/BPS (2.4 [1.7]) tissues than in control tissues (0.1 [0.3]; both P < 0.05). Tissues from the KC bladders had significantly lower expression of E-cadherin (P = 0.024) and significantly higher numbers of apoptotic cells (P = 0.02) compared with the IC/BPS bladder tissues. Greater numbers of apoptotic cells and lower expression levels of E-cadherin significantly correlated with maximum bladder capacity in the overall patient samples (P < 0.05).


KC and IC/BPS tissues both showed defective junction protein, increased suburothelial inflammation and increased urothelial cell apoptosis. Decreased expression of E-cadherin and increased apoptosis were more severe in KC than in IC/BPS bladder tissues and these findings were associated with the clinical symptoms of KC and IC/BPS.


apoptosis; bladder dysfunction; inflammation; ketamine; urothelium

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