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Simultaneous treatment with benzyl isothiocyanate, a strong bladder promoter, inhibits rat urinary bladder carcinogenesis by N-butyl-N-(4-hydroxybutyl)nitrosamine.

Effects of benzyl isothiocyanate (BITC) on urinary bladder carcinogenesis were examined in rats simultaneously treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Groups of 20 6-wk-old Fischer 344 male rats were given 10, 100, or 1,000 ppm BITC in the diet or a basal diet with 50 ppm BBN in the drinking water for 40 wk and then killed for autopsy. Additional groups consisting of 10 or 9 rats were similarly given BITC or the basal diet alone without BBN treatment. With BBN treatment, dysplasia, papilloma, and carcinoma incidences and multiplicities were dramatically decreased by simultaneous treatment with BITC in a clear dose-dependent manner. In contrast, epithelial hyperplasia was induced in rats treated with 100 and 1,000 ppm BITC without BBN. These results clearly indicate that although BITC may have weak carcinogenic potency, it is a potent chemopreventive agent against bladder tumor induction by BBN.

Animals↗

Ventral hernia of the urinary bladder with mixed urinary incontinence: treatment with herniorrhaphy and allograft fascial sling.

Abdominal hernias are not rare in women with urinary incontinence, but incisional bladder hernia is uncommon. The presenting symptoms in the rare cases reported included suprapubic discomfort, irritative voiding symptoms, and urinary incontinence. We present a patient with bladder herniation and severe mixed urinary incontinence. The pathophysiology of the urinary symptoms and the surgical alternatives for the correction of this condition are discussed.

Aged↗

[Transplantable cancer of the urinary bladder and hemangiopericytoma obtained by means of the ectopic transplantation of tissues of the fetal urinary bladder].

Organ-like cysts appear to develop after subcutaneous transplantation of minced tissues of fetal urinary bladder into adult syngeneic recipients. These are multilocular cysts lined with epithelium and filled with secretion. Many months later they undergo a spontaneous malignant tranformation. Transplantable strains of vesical cancer and hemangiopericytoma have been obtained.

Animals↗

Bladder-neck repair in urinary bladder exstrophy.

A simple modification of an existing technique for bladder-neck reconstruction in exstrophy of the urinary bladder is reported. The technique involves tubularization of the posterior urethra up to just below the ureteric orifices. It differs from other techniques in that no part of the bladder tissue is used for buttressing the repair, but all is utilized for enhancing the bladder volume. Only 2 of 20 patients remained incontinent after bladder-neck reconstruction; the remaining 18 have achieved socially acceptable continence.

Bladder Exstrophy↗

Barbital sodium, a tumor promoter for kidney tubules, urinary bladder, and liver of the F344 rat, induces persistent increases in levels of DNA synthesis in renal tubules but not in urinary bladder epithelium or hepatocytes.

The nephrotoxicity of barbital sodium (NaBB), a renal and urinary bladder tumor promoter, was investigated in male F344/NCr rats. In an 8-week toxicity study, NaBB was administered to 6-week-old male rats for 8 weeks at dietary levels of 16,000, 8000, 4000, 2000, 1000, or 0 ppm. Rats tolerated NaBB at levels of 4000 ppm and below with no weight depression or mortality. Liver-to-body weight ratios, however, were significantly increased at 4000 ppm, and toxic renal lesions were observed histologically. Light microscopic studies of male rats fed 1000 ppm NaBB for 2-52 weeks or 4000 or 8000 ppm for 8 weeks revealed elevated levels of DNA synthesis in renal tubular cells as measured with tritiated thymidine autoradiography or 5-bromo-2'-deoxyuridine immunohistochemistry that were associated with degenerative and regenerative nephrotoxic lesions. Increased labeling indices of urothelium and hepatocytes were not seen in rats exposed to 1000 ppm NaBB which is effective as a bladder and liver tumor promoter at these doses. These studies provide evidence for the chronic nephrotoxicity and renal tubular hyperplasia induced by NaBB in F344 rats, which are associated with the tumor-promoting activity of NaBB at the doses studied. Hyperplasia in the urinary bladder or liver was not found, however, for this bladder and liver tumor promoter. The conflicting findings in liver, bladder, and kidney are discussed.

Animals↗

The reliability of urinary cytology in the detection of tumours of urinary bladder.

Detection of urinary bladder tumours by cytological examination of urine was carried out on 193 patients suffering from haematuria. The patients comprised 149 new cases and 44 follow-up cases previously diagnosed as bladder cancer. Urinary bladder malignancy was detected in 72 of new cases and 20 of follow-up cases by cytological examination of urine. Reliability of the findings was checked by histopathological examination of the biopsy material removed from bladder by cystoscopy which detected malignancy in 84 of new cases and 16 of follow-up cases. Thus the sensitivity of cytological examination of urine in detecting bladder malignancy was 92% and specificity of 88%. False positive result was 4% and false negative result was 12%.

Adenocarcinoma↗

Biochemical and morphological effects of bladder pumping on the urinary bladder in rats.

AIMS: To study the influence of bladder pumping on the urinary bladder in 44 female rats. METHODS: Under halothane anesthesia, a urethral catheter was inserted into the bladder of 27 rats, and air (0.4-0.8 mL) was pumped in and out of the bladder at 0.5 cycles/second for a period of 5 minutes. Twenty-four hours after pumping, the bladder was harvested for measurement of the tissue levels of myosin, actin, and nerve growth factor, as well as for electron microscopy. In nine of the 27 rats, cystometry was performed without anesthesia before and 1, 7, 30, and 90 days after bladder pumping. The remaining 17 rats that did not undergo pumping were anesthetized and their bladders were harvested as a control. RESULTS: Bladder pumping increased the bladder capacity and decreased the maximum bladder contraction pressure, but did not increase the residual volume. Bladder pumping also increased the tissue level of nerve growth factor and decreased the levels of myosin and actin. Electron microscopy showed degeneration of bladder smooth muscle cells and nerve fibers after bladder pumping, as well as derangement and disruption of collagen fiber bundles in the bladder wall. These functional and morphological effects of pumping disappeared within 90 days. CONCLUSIONS: Bladder pumping therapy appears to have various effects on the bladder wall collagen fiber bundles, smooth muscle cells, and nerves.

Actins↗

Development of an experimental model for studying bladder carcinogen metabolism using the isolated rat urinary bladder.

The isolated rat urinary bladder was used to study this organ's capacity to metabolize chemical carcinogens. In our experimental conditions, the urinary bladder carcinogen N-nitrosobutyl(4-hydroxybutyl)amine was oxidized to N-nitrosobutyl(3-carboxypropyl)amine. A time-dependent increase was observed in the amount of N-nitrosobutyl(3-carboxypropyl)amine formed and simultaneous disappearance of N-nitrosobutyl(4-hydroxybutyl)amine added, indicating that the bladder can metabolize N-nitrosobutyl(4-hydroxybutyl)amine to the metabolite considered responsible for tumor induction in the urinary bladder of laboratory animals. At 15, 30, 60, and 120 min the percentages of N-nitrosobutyl(3-carboxypropyl)amine formed were 11, 22, 36, and 64%, respectively, and 62, 48, 37, and 26% of N-nitrosobutyl(4-hydroxybutyl)amine remained unchanged. When N-nitrosodibutylamine was introduced into the isolated urinary bladder and incubated for 120 min, its oxidized metabolites N-nitrosobutyl(4-hydroxybutyl)amine and N-nitrosobutyl(3-carboxypropyl)amine were formed, amounting to, respectively, 0.13 and 0.06% of the substrate added. The glucuronide of N-nitrosobutyl(4-hydroxybutyl)amine was incubated in the isolated rat urinary bladder both as a buffer and as a urine solution in order to detect cellular and urinary beta-glucuronidase activity. In both systems N-nitrosobutyl(4-hydroxybutyl)amine released was about 1% at 4 h and this percentage did not increase at 6 h. N-Nitrosobutyl(3-carboxypropyl)amine was detectable at 2 h and reached 0.2% of the substrate incubated at 6 h. The results indicate that the urinary bladder may play a role in activating bladder carcinogens.

Animals↗

Endothelin-1 and urinary bladder hyperplasia following partial bladder outlet obstruction.

Urinary bladder hypertrophy and hyperplasia is a common feature of bladder outlet obstruction (BOO). The urinary bladder is known to synthesize endothelin-1 (ET-1). ET-1 is a potent vasoconstrictor peptide with mitogenic properties. Using an animal model of partial BOO we investigated the potential role of ET-1 and its receptor subtypes [endothelin-A and -B (ET(A) and ET(B))] in bladder vascular smooth muscle cells (SMC) proliferation. In the presence of 3-week-old BOO serum, ET(A) and ET(B) antagonists significantly (p = 0.008) inhibited detrusor and bladder neck SMC proliferation. Cell counts were significantly reduced from the detrusor (p = 0.03, p = 0.01 with ET(A) and ET(B) antagonists, respectively) and bladder neck (p = 0.01 for both ET(A) and ET(B) antagonists). These results suggest that ET-1 antagonists may prevent SMC hyperplasia associated with partial BOO.

Animals↗

Evaluation of urinary bladder cancer antigen as a marker for diagnosis of transitional cell carcinoma of the urinary bladder.

The purpose of the present study was to assess a new quantitative urinary tumor marker for transitional cell carcinoma of the urinary bladder (TCC), measuring fragments of cytokeratin 8 and 18 in the urine (UBC). Urine samples of 355 individuals (77 healthy volunteers, 111 patients with benign urologic disorders, 167 patients with histologically proven bladder cancer) were examined for the presence of UBC antigen. Samples of all patients were obtained prior to therapy. Compared to healthy volunteers or patients with benign urologic disease, patients with TCC had significantly higher median urinary levels of UBC antigen (0 vs. 4.18 vs. 7.46 microg/g creatinine; p<0.001, and p<0.01, respectively). UBC antigen levels were positively correlated with tumor grade and stage. Patients with invasive TCC had significantly higher levels of UBC antigen than patients with superficial TCC (p<0.001). Elevated levels of UBC antigen were also found in patients with benign urologic disorders (median: 4.18 microg/g creatinine vs. 7.46 microg/g creatinine in cancer patients). Using a cutoff of 14.06 microg/g creatinine (corresponding to 95% specificity in the group of healthy individuals), sensitivity of UBC antigen ranged between 21.6% (pTa) and 75% (pT4). Overall specificity was 76.6%. Based on our data we conclude that the UBC antigen test in its current format is not clinically useful for detection of bladder cancer.

Antigens, Neoplasm↗

Interaction of tachykinins with an adrenergic receptor in the rat urinary bladder.

The rat urinary bladder was examined as a model for studying tachykinin receptors. The order of potency, the maximal effect and the slope of the dose-response curve were examined with six tachykinins - substance P (SP), physalaemin, phyllomedusin, uperolein, eledoisin, kassinin - and several substance P fragments - SP-(2-11), SP-(3-11), SP-(4-11) and SP-(6-11). The tachykinin receptor on the rat urinary bladder was shown to bind preferentially tachykinins having a hydrophilic amino acid residue in position 5-6, as occurs with physalaemin, phyllomedusin, eledoisin and kassinin. The N-terminal of the tachykinins and in particular substance P is suggested to play a major role in regulating affinity, intrinsic activity and the slope of the dose-response curve. The tachykinins are thought to exert a direct action on smooth muscle. An accessory binding site associated with the tachykinin receptor on rat urinary bladder was also identified. This accessory site binds the N-terminal amino acids of the tachykinins as well as some alpha-adrenergic compounds (phentolamine, prazosin, noradrenaline or adrenaline in the presence of propranolol). When the accessory binding site is occupied by adrenergic compounds, the affinity of the tachykinins is markedly reduced. This observation is interpreted to mean that catecholamines may have a modulatory influence on tachykinin activity on the rat urinary bladder.

Animals↗

Mouse models of short- and long-term foreign body in the urinary bladder: analogies to the bladder segment of urinary catheters.

Catheter-associated bacteriuria is the most common infection occurring in hospitals, where urethral catheters are generally in place for a few days, and in nursing homes, where catheters may be in place for months or years. We developed murine models with intrabladder urinary catheters for studying complications of bacteriuria in short- and long-term catheterization. In the short-term model, a catheter segment was inserted transurethrally and lay free within the bladder lumen. Half of the animals expelled segments during a 2-to-7-day period, durations similar to catheterizations in hospitalized patients. For studies of long-term catheter use, the catheter segment was secured within the bladder by a single suture for up to 12 months. Antibiotics administered for 7 days after catheter placement and housing mice in cages with wire screen floors reduced spontaneous bacteriuria to an acceptably low incidence rate of only 7%. Proteus mirabilis bacteriuria of high concentration provoked the same complications that are common in patients with long-term catheters: acute pyelonephritis, chronic renal inflammation, and struvite stone formation. These models allow inoculation of the bacteria of interest and are suitable for studies of short- and long-term foreign body-associated bacteriuria and its complications.

Animals↗