Sulfated polysaccharide's ability to modulate the movement of small molecules was examined both in vivo and in vitro. For the in vivo test, the rabbit bladder was utilized and C-14 labeled urea 45-Ca, or 3H2O was placed into the lumen of control bladders, bladders pretreated with protamine sulfate (20 mg./cc) and bladders pretreated with protamine sulfate (20 mg./cc) plus pentosanpoly-sulfate (PPS), 10 mg./cc. After 45 minutes, the controls absorbed 21% of the urea, 16% of the calcium, and 38% of the 3H2O; the protamine treated group 40% urea, 23% calcium, and 51% H2O; the PPS only group 22% urea and the protamine plus PPS group absorbed 24% of urea, 18% calcium, and 44% water. Differences between the control and protamine groups were statistically significant, p less than 0.01 for urea 45-Ca and 3H2O. The bladder mucosa contained a significantly higher concentration of urea and calcium after protamine treatment which were both reversed by PPS (p less than 0.01) while 3H2O content went down significantly (p = 0.03), reflecting a loss of the hydrophilic effect of bladder GAG. The control mucosas had 250 cpm/mg. tissue urea for Ca 64 cpm/mg. and water 262 cpm/mg., the protamine group urea 498 cpm/mg., Ca 190 cpm/mg., and H2O 139 cpm/mg.; the protamine plus PPS group urea 344 cpm/mg., Ca 129 cpm/mg., and water 168 cpm/mg. For the in vitro studies, an Ussing chamber was employed. Normal rabbit bladder membranes were placed in the chambers and the potential difference was zeroed across the membrane. There were three groups, membranes that were treated only with the irrigating solution, membranes pretreated with protamine, and membranes pretreated with protamine plus PPS. At the end of 40 minutes, there was an approximately 1.2% movement of urea across the control membrane, a 3.5% movement across the protamine treated membrane (a significant increase p less than 0.001) and a 1.1% movement across the protamine plus PPS treated membrane. It would appear that the surface polysaccharide may play an important role as a bladder permeability barrier in modulating both charged and uncharged small molecule movement in that its ability to impair such movement can be inhibited by protamine and this protamine effect can be reversed by a treatment with an exogenous sulfated polysaccharide.

The findings reported strongly suggest abnormal differentiation in the IC bladder. The disruption of ZO-1 is similar to that reported in feline IC. Elevated E-cadherin may represent an adaptation to increased bladder permeability.

This study confirmed several previously reported urine alterations in interstitial cystitis, including increased anti-proliferative factor, epidermal growth factor, IGF binding protein-3 and IL-6, and decreased heparin-binding epidermal growth factor-like growth factor and cyclic guanosine monophosphate. Of all markers studied anti-proliferative factor had the least overlap in the interstitial cystitis and control groups, and so it is the most likely candidate to become a diagnostic test.

Findings strongly suggest abnormal differentiation in the interstitial cystitis urothelium with a loss of barrier function markers and altered differentiation markers being independent and occurring independently of inflammation. Loss of the glycosaminoglycan layer was associated with a loss of biglycan and perlecan on the luminal layer.

The roles of glycosaminoglycans and proteoglycans in the physiology of the urinary tract are reviewed. The structures of proteoglycans and glycosaminoglycans are reviewed together with their role in control of epithelial differentiation through stromal-epithelial interactions and as modulators of cytokines. Heparan sulfate proteoglycans appear to be important in maintaining selectivity of the kidney tubular basement membrane, and the majority of the glycosaminoglycan found in the urine appears to come from the upper tract. Evidence suggesting that a dense layer of glycosaminoglycans on the urothelial surface is important to maintaining urothelial impermeability is reviewed and new data showing a high density of proteoglycans on the lumenal surface of the urothelium is presented. The role of this layer in maintaining antibacterial adherence and impermeability was discussed together with data suggesting that failure of this layer is an etiologic factor in interstitial cystitis. A model of the bladder surface is also presented to illustrate the role of proteoglycans and exogenous glycosaminoglycans in the defenses of normal bladder lumen and the failure of these defenses in the interstitial cystitis bladder.

BACKGROUND-Human prostate cancer LNCaP and PC-3 cell lines have been extensively used to study prostate cancer progression and to develop therapeutic agents. Although LNCaP and PC-3 cells are generally assumed to represent early and late stages of prostate cancer, respectively, there is limited information regarding gene expression patterns between these two cell lines and its relationship to prostate cancer.

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RE, Saban R. VEGF receptors and neuropilins are expressed in the urothelial and neuronal cells in normal mouse urinary bladder and are upregulated in inflammation. Am J Physiol