Three major hypotheses will be investigated in interstitial cystitis. Experimental and clinical studies will focus on the interaction between urine and transitional epithelium. Preliminary evidence has indicated that urine from IC patients may contain toxic component(s) not present in normals and that the bladder mucosa has an altered permeability which can be measured clinically in humans and rodents by urea leakage. These two observations may provide a new approach for investigating the etiology of this disorder. A key strength of this proposal is the ability to utilize the large patient base of an established IC investigator (130-150) new patients/year). Clinical specimens from these patients will provide a well controlled source of pathological material (urine, bladder biopsy tissue and serum) for research investigations that will test our hypotheses: 1). Interstitial cystitis patients have a dysfunctional """"""""leaky"""""""" epithelium: We shall both improve and utilize our human in vivo measure of epithelial permeability to determine if the glycosaminoglycans (heparin) can restore the bladder """"""""blood-urine barrier"""""""" in IC patients. 2). Tissue culture methods can be developed to provide a source of transitional epithelial cells from IC patients for research investigations: We have developed methods to grow IC transitional cells and mucosal explants in culture. These methods will be used to examine the cells and explants for anatomic (EM) and protein markers of differentiation. The effect of IC urine on these findings will be examined and compared to control urines. 3). Urine from IC patients has a cytotoxic component(s): Normal urine does not appear to have in vitro cytotoxicity. We will pursue the abnormality of urine in IC patients that causes epithelial injury and determine whether it is abnormally present in urine, or a normal substance not adequately inactivated by natural urinary defense mechanisms in the IC patients. Both Tamm-Horrrsfall Protein (THP) and glycosaminoglycans (GAG) will be investigated as possible compounds that may inactivate noxious agents (by binding to them). Preliminary data shows that both THP and GAG are capable of such activity.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
Project #
Application #
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Diego
Schools of Medicine
La Jolla
United States
Zip Code
Akiyama, A; Stein, P C; Houshiar, A et al. (2000) Urothelial cytoprotective activity of Tamm-Horsfall protein isolated from the urine of healthy subjects and patients with interstitial cystitis. Int J Urol 7:176-83
Parsons, C L; Greenberger, M; Gabal, L et al. (1998) The role of urinary potassium in the pathogenesis and diagnosis of interstitial cystitis. J Urol 159:1862-6;discussion 1866-7
Tay, H; Parsons, C L; Stein, P C (1996) Electrophysiologic monitoring of the effects of soluble virulence factors produced by Escherichia coli infection in urine. Urology 48:389-92
Stein, P C; Pham, H; Ito, T et al. (1996) Bladder injury model induced in rats by exposure to protamine sulfate followed by bacterial endotoxin. J Urol 155:1133-8
Tay, H P; Bidair, M; Shabaik, A et al. (1995) Primary yolk sac tumor of the prostate in a patient with Klinefelter's syndrome. J Urol 153:1066-9
Mostafavi, M; Stein, P C; Parsons, C L (1995) Production of soluble virulence factor by Escherichia coli. J Urol 153:1441-3
Niku, S D; Scherz, H C; Stein, P C et al. (1995) Intestinal de-epithelialization and augmentation cystoplasty: an animal model. Urology 46:36-9
Stein, P C; Parsons, C L (1994) Proteoglycan core protein syndecan in bladder biopsies. World J Urol 12:15-20
Parsons, C L (1994) A model for the function of glycosaminoglycans in the urinary tract. World J Urol 12:38-42
Teichman, J M; Abraham, V E; Stein, P C et al. (1994) Protamine sulfate and vancomycin are synergistic against Staphylococcus epidermidis prosthesis infection in vivo. J Urol 152:213-6

Showing the most recent 10 out of 22 publications