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Title: An investigation into the effects of short-chain fatty acids on primary and transformed urothelial cells in relation to their potential as an intravesical agent in the neobladder
Author: Dyer, Jonathan Paul
Awarding Body: University of Southampton
Current Institution: University of Southampton
Date of Award: 2007
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Abstract:
Colocystoplasty has an important role in bladder reconstructive surgery. However it can be affected by chronic inflammation and excessive mucous production which may lead to urinary tract infectioh, stone formation and occasionally malignant.transformation. We postulate that changes in the colonic segment within the augmentation are affected by a condition known as diversion colitis, which is found in bowel segnients diverted away from the faecal stream. The aetiology ofthis condition is a luminal deficiency ofshort chain fatty acids (SCFAs) which are produced by bacterial fermentation ofdietary fibre and include butyrate, propionate and acetate. Studies have shown that they are the colonocytes' preferred energy substrate and have an important role in colonic mucosal health andprevention of malignant transformation. The purpose ofthis study was to investigate the effect ofSCFAs on the bladder which is an .important consideration when contemplating intravesical therapy in colocystoplasty. Using monolayer cell cultures ofboth primary urothelial cells and urothelial cancer cell lines the effects of SCFAs were inves~igated. The MIT (3-[4,5-dimethyl thiazol-2-yl]-2,5-diphenyltetrazolium bromide; thiazolyl blue) cytotoxicity assay was employed to study cell growth. Fluorescence microscopy with acridine orange and flow cytometry were used to study apoptosis and the cell cycle. It was found that all three SCFAs inhibit cell growth, induce apoptosis and induce cell cycle arrest. Butyrate had the' most potent effect in vitro followed by propionate and then acetate. To assess the significance ofthese results in vivo, intravesical instillation of SCFAs was performed in a rodent model which demonstrated no significant adverse effects both histologically and on urothelial cell turnover.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.484855  DOI: Not available
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