The bladder surface is remarkably resistant to disease. It interacts with urine that potentially contains bacteria, carcinogens, inflammatory-inducing substances and microcrystals. Prior studies would suggest that one important defense is the presence of a non-specific antiadherence factor, surface glycosaminoglycans. This antiadherence phenomenon can be reproduced by several exogenously supplied sulfated polysaccharides, heparin and pentosanpolysulfate (PPS). These substances reduce the adherence of bacteria, proteins, ions and microcrystals to the bladder. PSS has been successfully employed to treat both radiation and interstitial cystitis. The rationale for its use in these conditions was based on the consideration that it could augment the bladder surface defenses. The current study is proposed to expand the understanding of surface and urinary polysaccharides in health and disease. It is felt that while the severe forms of interstitial cystitis are rare, this disease may reveal important information concerning the defense mechanism of transitional epithelium. IC Is postulated to result from surface problems resulting in """"""""leaks"""""""" such that urinary constituents reach the submucosal and trigger an inflammatory response. This response may ultimately lead to a form of autoimmune activity. Polysaccharide offers potential to """"""""plug"""""""" the leaks by their hydrophilic antiadherence activity and/or ameliorate the inflammation. The knowledge of metabolism of polysaccharides within the GU tract is embryonic. Preliminary data has shown that IC patients have only 1/3 of the PS level in their bladders that controls have but interestingly have much higher ureteral levels. This suggests the epithelium is removing urinary PS and is either a defense mechanism, sign of a sick epithelium, or perhaps even a cause of the problem. It is proposed to study the role of exogenous PS in IC while studying the metabolism of PS within the urinary tract. Mechanisms of PS movement across normal and """"""""abnormal"""""""" epithelium will be examined as well as ways to promote and hinder movement. IC patients will be examined in an attempt to isolate urinary substances capable of """"""""inducing"""""""" leaks, as well as ways to block these inducers. PS metabolism will be tracked within the urinary tract to find the role of the level excreted, epithelial synthesised compounds in health and disease.
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