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Understanding mechanisms of Ketamine-induced human urinary tract damage

Shahzad, Khurram (2011) Understanding mechanisms of Ketamine-induced human urinary tract damage. MSc by research thesis, University of York.

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Ketamine is a phencyclidine derivative N-Methyl D-Aspartate (NMDA) receptor antagonist used as an anaesthetic and analgesic. A florid non-bacterial cystitis condition known as ketamine-induced cystitis (KIC) has recently been reported in abusers and prescription users of ketamine. Whilst the aetiological agent in patients withKIC is known, the mechanism of disease development is unknown. The aims of this study were to investigate the potential mechanisms of development of KIC and to establish potential links between KIC and other chronic non-bacterial cystitis conditions; interstitial cystitis (IC) and eosinophilic cystitis (EC). These aims were pursued under the following objectives; 1. Investigate toxicity of ketamine and its primary metabolite nor-ketamine on normal human urothelial (NHU) cell cultures. 2. Describe human urothelial tissue damage caused by ketamine. 3. Assess a possible relationship between ketamine exposure and development of KIC. The main findings were that; Ketamine and nor-ketamine were equally toxic to NHU cells in a concentration dependent manner. A specific NMDA receptor antagonist (MK-801) did not show any urothelial toxicity on its own but unexpectedly increased toxicity of ketamine when used in combination. Immunolabelling of the three individual KIC tissue sections demonstrated epithelial denudation and stromal inflammation with oedematous blood vessels. Results from a telephone questionnaire did not show any obvious relationship between prescription use of ketamine and development of KIC. Literature review suggested considerable similarities between the reported symptoms and clinical investigation findings of KIC to mainly EC and to some extent to IC. In conclusion, the study indicated that ketamine might cause human urinary tract damage by impairing the barrier function of urothelium, inducing inflammation and resultant development of KIC. These experiments should form the basis for future research in to understanding the mechanisms of development of KIC and other difficult to treat chronic uropathies such as EC and IC.

Item Type: Thesis (MSc by research)
Keywords: Ketamine Ketamine-induced cystitis Human urinary tract
Academic Units: The University of York > Biology (York)
Depositing User: Khurram Shahzad
Date Deposited: 27 Feb 2012 10:12
Last Modified: 08 Aug 2013 08:48
URI: http://etheses.whiterose.ac.uk/id/eprint/2104

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