A new direct test of bladder permeability.

PURPOSE: A proposed cause of interstitial cystitis is increased bladder permeability but to our knowledge this theory has not been proved by direct testing. We developed a safe, relatively painless, direct test of bladder permeability. MATERIALS AND METHODS: The original permeability test involved placing 4% lactulose and 1% rhamnose intravesically, then drawing blood to assay for these sugars. Initial feasibility studies were performed in rabbits with bladder epithelium that was intact or disrupted by a 50% acetone rinse. In humans the initial goal was to distinguish intact bladders from those known to have increased permeability. Since distention is known to increase permeability temporarily, we studied patients with interstitial cystitis immediately after distention. RESULTS: Neither sugar was absorbed from intact rabbit bladders, while each was absorbed from acetone rinsed bladders at 10, 20 and 30 minutes. We used 100 ml. of solution in the initial 8 humans, including 6 with interstitial cystitis and 2 controls. At 30 minutes each sugar was absorbed from interstitial cystitis bladders but neither was absorbed from intact bladders. The test solution was then changed to 5% rhamnose. Mean rhamnose absorption plus or minus standard deviation was much greater in the 6 patients with interstitial cystitis than in 8 controls (26.3 + or - 26.1 versus 0.78 + or - 0.87 nmol. /ml. serum, p = 0.008). With 1 exception interstitial cystitis serum levels were at least 4-fold higher than the highest control level. CONCLUSIONS: This new permeability test clearly distinguishes intact versus distended bladders. It may be performed to test whether bladder permeability is increased in interstitial cystitis.

Lectin histochemical examination of rabbit bladder glycoproteins and characterization of a mucin isolated from the bladder mucosa.

The glycocalyx of the mucosal surface of urinary bladder acts as an effective barrier against invasion by pathogenic microorganisms and injury from toxic substances in the urine. Defects in these bladder mucosal components could thus be important factors in the development of diseases such as interstitial cystitis and lower urinary tract infections. However, information on the nature of glycoconjugates of mammalian bladder mucosa is very limited. In this study, the glycoconjugates of rabbit bladder were examined histochemically using biotinylated lectins with specificities for a variety of carbohydrate moieties. Three [Artocarpus integrifolia (Jacalin), Datura stramonium (DSL), and Maackia amurensis II (MAL-II)] of the lectins bound predominantly to the luminal cell layer, with decreased binding to the basal layers of the epithelium. In contrast, Ricinus communis I and Sambucus nigra lectins did not bind to the cells in the epithelium but strongly interacted with the subepithelial layers, especially the lamina propria. The intensity of the staining by Jacalin and MAL-II was significantly reduced by prior treatment of the bladder sections with O-sialoglycoprotein endopeptidase, indicating that the ligands of these lectins are primarily mucin glycoproteins. In parallel biochemical studies, a high-molecular-weight glycoprotein with characteristics typical of epithelial mucins was purified from the mucosa of rabbit bladder explant cultures metabolically labeled with [(3)H]glucosamine. Quantitative analysis of the sialic acid, uronic acid, and hexosamine contents of delipidated rabbit bladder mucosa revealed a larger proportion of sialoglycoproteins compared with glycosaminoglycans. Taken together, the results of histochemical and biochemical analyses indicate that glycoproteins rather than glycosaminoglycans are the major components of the bladder epithelium, and that the former include a mucin.