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PubMed2003

Expression and functional role of Rho-kinase in rat urinary bladder smooth muscle.

(1) The involvement of Rho-kinase (ROCK) in the contractile mechanisms mediating smooth muscle contraction of the rat urinary bladder was investigated using expression studies and the ROCK inhibitor Y-27632. (2) Both isoforms of ROCK (ROCK I and ROCK II) were detected in high levels in rat urinary bladder. (3) Y-27632 (10 micro M) significantly attenuated contractions of rat urinary bladder strips evoked by the G-protein coupled receptor agonists carbachol (58.1+/-10.5% at 0.3 micro M) and neurokinin A (68.6+/-12.7% at 1 micro M) without affecting contractions to potassium chloride (10-100 mM). In addition, basal tone was reduced by 47.8+/-2.0% by 10 micro M Y-27632 in the absence of stimulation. (4) Contractions of urinary bladder strips evoked by the P2X receptor agonist alpha,beta-methylene ATP (alpha,beta-mATP; 10 micro M) were also attenuated by Y-27632 (30.0+/-7.2% at 10 micro M). (5) Y-27632 (10 micro M) significantly attenuated contractions evoked by electrical field stimulation (2-16 Hz). The effect of Y-27632 on the tonic portion of the neurogenic response (4-16 Hz) was not significantly different from the effect of atropine (1 micro M) alone. (6) While the mechanism underlying the ability of Y-27632 to inhibit alpha,beta-mATP-evoked contractions remains undetermined, the results of the present study clearly demonstrate a role for ROCK in the regulation of rat urinary bladder smooth muscle contraction and tone.

Animals↗
PubMed2003

Protease-activated receptor-2-mediated contraction of urinary bladder is enhanced in cyclophosphamide-treated rats.

Protease-activated receptor-2 (PAR-2) is activated by serine proteases, such as trypsin and mast cell tryptase. Recently, we have shown that activators of PAR-2 contract the rat urinary bladder mainly by stimulating release of prostaglandins (PGs) from the mucosal layer. In the present study, we investigated how the PAR-2-mediated responses are altered in rats with cyclophosphamide (CYP)-induced cystitis. The contractile responses to trypsin and PAR-2 activating peptide (PAR-2 AP; SLIGRL-NH2) in the urinary bladders were augmented by treatment of rats with CYP. The contractile effects of these PAR-2 activators on the smooth muscles of the urinary bladder were also potentiated after induction of cystitis by CYP. On the other hand, CYP-induced cystitis significantly attenuated contractions produced by PGE2 in the smooth muscles of the urinary bladder. The PAR-2-mediated contractions were significantly prevented by indomethacin or NS-398, an inhibitor of cyclooxygenase-2. Both trypsin and PAR-2 AP increased the release of PGE2 from the urinary bladder mucosa and smooth muscle. CYP-induced cystitis enhanced the PAR-2 activators-induced PGE2 releases from the urinary mucosa without affecting those from the smooth muscle of the urinary bladder. The PGE2 releases were prevented by indomethacin or NS-398. The mRNAs for PAR-2 in the urinary bladder mucosa and smooth muscle preparations were not altered in CYP-induced cystitis. These results suggest that PAR-2-mediated responses were enhanced in bladders from CYP-treated rats. The enhancement of PAR-2-mediated contraction might be ascribed to the increased production of PGs and the altered sensitivity of smooth muscle to PAR-2 activators.

Animals↗
PubMed1995

Villous adenoma of the urinary bladder: a case report.

A case of villous adenoma of the urinary bladder is described. The patient, a 57-year-old Chinese male, presented with a long-term history of urethral stricture disease secondary to gonorrhea urethritis. On cystoscopic examination, a mucin-secreting papillary tumor, measuring 3 x 2 cm was noted at the bladder neck. Microscopically, there were papillary fronds of mucin-secreting columnar cells with varying degrees of piling up. The relationships between chronic irritation of the urinary bladder, cystitis glandularis, intestinal metaplasia, villous adenoma and adenocarcinoma were discussed.

Adenoma, Villous↗
PubMedDate not supplied

Chemoprevention by indomethacin of N-butyl-N-(4-hydroxybutyl)-nitrosamine-induced urinary bladder tumors.

The effects of indomethacin on the development of N-butyl-N-(4-hydroxybutyl) nitrosamine (OH-BBn)-induced urinary bladder tumors were evaluated in male BDF mice. Preliminary feeding studies revealed that the highest non-toxic dose of indomethacin was 15 mg/kg of AIN-76A diet; thus, dose levels of 15 and 7.5 mg/kg of diet were selected to determine the chemopreventive efficacy of this agent. Diet supplementation with indomethacin was initiated when the mice were 49 days old and continued for the duration of the study. Starting one week after indomethacin treatment, OH-BBN was administered 1x/week for eight weeks. Upon termination of the study (180 days after the initial carcinogen administration), all tumors in the urinary bladder were removed and classified histologically. Mice receiving carcinogen and no indomethacin supplementation had a 24% incidence of urinary bladder tumors; mice receiving 7.5 mg/kg and 15 mg of indomethacin had a 5% and 0% incidence of urinary bladder tumors, respectively. The significant reduction of OH-BBN-induced urinary bladder tumors by indomethacin is consistent with previous suggestions that prostaglandin synthesis inhibitors are effective inhibitors of carcinogenesis.

Animals↗
PubMed2002

Renal cell carcinoma with solitary metachronous metastasis to the urinary bladder.

We report a case of renal cell carcinoma with solitary metachronous metastasis to the urinary bladder occurring 6 years after radical nephrectomy. The patient was treated with partial cystectomy and survived for 60 months. Other cases like this one were reviewed in published reports, and the 3-year survival rate for patients with this type of cancer with solitary metastasis to the urinary bladder was found to be 80%. The follow-up duration of our case was the longest in the published studies. We suggest that urinary bladder metastasis of renal cell carcinoma should be resected because no effective treatment for metastatic renal cell carcinoma is available. A good prognosis may be expected, especially in patients with solitary metastasis to the urinary bladder.

Aged↗
PubMed2005

Small cell carcinoma of the urinary bladder. The Mayo Clinic experience.

BACKGROUND: Small cell carcinoma (SCC) of the urinary bladder accounts for 0.35-0.70% of all bladder tumors. There is no standard approach to the management of SCC of the urinary bladder. METHODS: The authors performed a retrospective study at Mayo Clinic (Rochester, MN) to characterize the clinical and pathologic features of patients with SCC of the urinary bladder diagnosed between 1975 and 2003 with emphasis on management. RESULTS: Forty-four patients were identified who had primary bladder SCC, 61.4% of whom had pure SCC. The male:female ratio was 3:1, the mean age was 66.9 years, and the mean follow-up was 3.2 years. Twelve patients (27.3%) had Stage II disease, 13 patients (29.6%) had Stage III disease, and 19 patients (43.2%) had Stage IV disease. The overall median survival was 1.7 years. The 5-year survival rates for patients with Stage II, III, and IV disease were 63.6%, 15.4%, and 10.5%, respectively. Six of eight patients with Stage II bladder SCC achieved a cure with radical cystectomy. Five patients with Stage IV disease had obvious metastases and received chemotherapy. Fourteen patients underwent radical cystectomy and were diagnosed later with locally advanced disease (T4b) or lymph node metastasis (N1-N3; Stage IV disease). Only 2 of 19 patients with Stage IV disease who received adjuvant chemotherapy were alive at 5 years. CONCLUSIONS: Patients with bladder SCC should undergo radical cystectomy except when metastatic disease is present (M1), in which case, systemic chemotherapy is indicated. Adjuvant treatment is not indicated for patients with Stage II disease after radical cystectomy but should be considered for patients with Stage III and IV disease. Chemotherapy should be a platinum-based regimen.

Age Distribution↗
PubMed2001

Capsaicin receptor VR1 and ATP-gated ion channel P2X3 in human urinary bladder.

OBJECTIVES: To determine the presence, distribution and molecular forms of the vanilloid receptor VR1, and confirm the presence and distribution of the ATP-gated ion channel P2X3 in the human urinary bladder. Materials and methods Normal urinary bladder tissues were obtained at postmortem from four subjects. Eight urinary bladder biopsies were also taken from patients with detrusor hyper-reflexia treated with intravesical resiniferatoxin. The specimens were studied using affinity-purified specific antibodies to VR1 and P2X3 by Western blotting and immunocytochemistry, and compared with immunostaining using antibodies to the pan-neuronal marker PGP 9.5 and Schwann cell marker S-100. RESULTS: VR1- and P2X3-immunoreactive fine nerve fibres were scattered throughout the suburothelium of the normal bladder and cystoscopic biopsies, and traversed the muscle layer. They had a similar distribution to PGP 9.5-immunoreactive fibres, but there were fewer, suggesting localization in subsets of axons. Western blot studies showed an expected 100-kDa VR1 protein and a P2X3-immunoreactive 66-kDa protein. Conclusion VR1 and P2X3 are present in the human urinary bladder and may contribute to distinct pathophysiological states of bladder overactivity, in accord with their differential expression in sensory neurones. Intravesical vanilloids act via VR1 and are effective in the treatment of detrusor hyper-reflexia. P2X3 may represent a selective therapeutic target for other causes of overactive bladder.

Adenosine Triphosphate↗
PubMed1994

Effects of cyclopiazonic acid on contractility and ecto-ATPase activity in guinea-pig urinary bladder and vas deferens.

1. Cyclopiazonic acid (CPA), an inhibitor of sarcoplasmic ATPase, was tested on guinea-pig urinary bladder and vas deferens for its ability: (1) to modify contractile responses to electrical field stimulation (EFS), exogenous ATP, alpha,beta-methylene ATP (alpha,beta-MeATP), carbachol, noradrenaline (NA), histamine, and KCl; (2) to affect ecto-ATPase activity; (3) to modify the release of ATP evoked by EFS. 2. In the urinary bladder, CPA (10 microM) potentiated contractile responses to EFS, exogenous ATP (100 microM), alpha,beta-meATP (1 microM), carbachol (0.5 microM), histamine (30 microM) and KCl (30 mM). In the vas deferens, CPA (10 microM) potentiated responses to EFS, ATP, alpha,beta-meATP, NA (100 microM) and KCl. CPA at a concentration of 1 microM had no effect on ATP-induced relaxation of carbachol-precontracted guinea-pig taenia coli, and at a concentration of 10 microM it markedly increased spontaneous contractile activity of taenia. 3. Ecto-ATPase was estimated to have Vmax and Km values of 0.98 nmol Pi 30 min-1 mg-1 wet tissue and 881 microM ATP in the urinary bladder, and 0.75 nmol Pi 30 min-1 mg-1 wet tissue and 914 microM ATP in the vas deferens, respectively. CPA at a concentration of 10 microM significantly inhibited ecto-ATPase activity by 18% in the urinary bladder and by 24% in the vas deferens. 4. In the guinea-pig vas deferens, CPA significantly potentiated ATP release evoked by EFS from 2.2 +/- 0.8 (6) pmol ATP min-1 g-1 wet tissue to 35.2 +/- 4.8 (6) pmol ATP min-1 g-1 wet tissue (P < 0.01). 5. In conclusion, the potentiation of contractile responses of the guinea-pig urinary bladder and vas deferens by CPA has a non-specific character. CPA inhibited ecto-ATPase activity and increased ATP release, but these effects do not appear to contribute to the potentiation of Pu-purinoceptor-mediated responses since the contractile actions of all the agonists studied were potentiated to the same extent.

Adenosine Triphosphatases↗
PubMed1987

Effect of distension of the urinary bladder on efferent cardiac sympathetic nerve fibres which respond to stimulation of atrial receptors.

The effect of distension of the urinary bladder on the activity in the efferent cardiac sympathetic nerves which responded to stimulation of atrial receptors or those which responded to stimulation of carotid baroreceptors or chemoreceptors, was studied in dogs anaesthetized with chloralose; the urinary bladder was distended with warm saline, small balloons were positioned at the right pulmonary vein-atrial junctions and distended with 1 cm3 saline, and the carotid sinuses were vascularly isolated and perfused with blood at constant flow. The efferent cardiac sympathetic nerve fibres which responded to stimulation of carotid baroreceptors and chemoreceptors by a decrease in activity always responded with an increase in activity in response to distension of the urinary bladder. In contrast, in those efferent cardiac sympathetic nerve fibres which did not respond to an increase in carotid sinus pressure, but responded to stimulation of atrial receptors by an increase in activity, distension of the urinary bladder neither caused a significant change in activity nor produced a reproducible pattern of response. It is concluded that the efferent cardiac sympathetic nerve fibres which respond to stimulation of atrial receptors are separate from those which respond to distension of the urinary bladder.

Animals↗
PubMed1981

Urinary bladder tumors induced by N-butyl-N-(4-hydroxybutyl)nitrosamine in dogs.

Clinicopathological, radiological, and histological studies were performed on urinary bladder neoplasia induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in five adult beagle dogs and in ten adult mongrel dogs. Tumors of the urinary bladder developed in dogs given various daily doses of BBN p.o. for different periods. The latent period of tumor induction was 4 years in dogs receiving a daily dose of 80 mg of BBN, 2 to 2.5 years in dogs receiving a daily dose of 160 mg of BBN, and 1.5 years in dogs receiving a daily dose of 240 mg of BBN. The total dose of BBN ingested by the dogs until the first tumors were observed by urological examinations was nearly the same in all groups, 100 to 140 g. These results suggest that there is a correlation between dose and induction time, but further dose-response studies are required. Histologically, tumors of the urinary bladder were transitional cell papillomas or transitional cell carcinomas resembling morphologically those found in human cases. It is possible to observe the process of development of urinary bladder tumors from initial lesions to invasive tumors using routine urological examinations. We believe that this experimental model is valuable for clinicopathological studies of urinary bladder tumors.

Animals↗
PubMed1998

Neuromuscular transmission and innervation in the urinary bladder of the insectivore Suncus murinus.

In isolated preparations of the urinary bladder detrusor of the house musk shrew Suncus murinus (order: insectivora; family: Soricidae), electrical field stimulation (0.5-32 pulses/s) evoked neurogenic contractile responses that were markedly attenuated by atropine (1 microM). The non-cholinergic component was reduced but not abolished by the P2-purinoceptor antagonist, suramin (300 microM). Thus, neuromuscular transmission in the suncus urinary bladder is effected by cholinergic and purinergic nerves together with an as-yet unidentified component. Using immunohistochemical methods, the suncus urinary bladder was seen to be supplied by nerves containing neuropeptide Y, tyrosine hydroxylase, vasoactive intestinal polypeptide, galanin, substance P, calcitonin gene-related peptide and type I nitric oxide synthase. The pattern of responses to electrical field stimulation was more similar to that of humans and Old World primates, than to that of rodents or lagomorphs. The pattern of innervation of the bladder wall, in terms of the distribution of populations containing a given neuropeptide, was very similar to that in humans. Hence, Suncus murinus may provide a novel species for modelling the neuropharmacology of the human bladder, and also for studying the evolution of autonomic innervation.

Animals↗
PubMed1997

Descriptive epidemiological assessment of urinary bladder & kidney cancers in Greater Bombay.

For studying the descriptive epidemiology of cancers of the urinary bladder and kidney, the data reported by Bombay Cancer Registry for the most recent five years have been utilised. For studying time trends in these cancers, data of the past 30 yr have been used. In Bombay, bladder cancer is very uncommon in the first three decades of life; but after the age of 30, the incidence rates increase with age, in log-linear fashion, in both sexes. The incidence of kidney cancer is almost absent between the ages 5 to 35; but later up to the age of 70, it show a steady increase. The incidence of urinary bladder and kidney cancers are found to be associated with the marital status in both sexes. No association was observed between the incidence and educational level attained by the patients having urinary bladder and kidney cancers. An increasing trend was found in the age adjusted incidence rates of cancers of the urinary bladder and kidney in both sexes during the period 1964-1993.

Adolescent↗
PubMed1993

Epithelia hyperplasia in the renal papilla and pelvis but not the urinary bladder of male F344 rats associated with dietary sodium phosphates after uracil exposure.

Effects of the bladder tumor promoter Na3PO4 and the non-bladder-tumor promoter NaH2PO4 on development of hyperplastic lesions of urinary bladder and renal papilla/pelvis were investigated after exposure of male F344 rats to the nongenotoxic carcinogen uracil. Animals were administered with 3.0% uracil in the diet for 4 weeks and thereafter fed 3.0% Na3PO4 or 3.0% NaH2PO4 for 32 weeks. No enhancing effect of either phosphate salt on uracil-induced proliferative lesions of urinary bladder was observed. However, the sequential treatments gave rise to enhanced development of hyperplastic lesions in the renal papilla/pelvis compared to the case with uracil alone. In addition, a small number of renal pelvic papillomas were observed in the group given Na3PO4 after uracil. These phosphate salts also induced nephrocalcinosis in the papilla/pelvis concomitant with development of renal hyperplastic lesions in this location. A sequential study revealed calculus formation and proliferative lesions in both the urinary bladder and renal papilla/pelvis after 4 weeks dietary application of uracil. After cessation, calculi disappeared and the majority of hyperplastic lesions regressed, consistent with a decrease in DNA synthesis levels. Persistence of uracil-induced epithelial hyperplasia in renal papilla/pelvis under the influence of phosphate salts might have been directly due to chronic stimulation by nephrocalcinosis in these sites.

Animals↗
PubMed1999

[Effect of liarozole on the cell proliferation activity in the rat urinary bladder epithelium induced by N-butyl-N-(4-hydroxybutyl) nitrosamine].

INTRODUCTION AND OBJECTIVES: Recently, the chemopreventive effects of various drugs on N-Butyl-N-(4-hydroxybutyl) nitrosamine (BBN) induced rat urinary bladder carcinogenesis have been reported. The aim of this study was to evaluate the effect of liarozole, an antitumor agent that inhibits the metabolism of retinoids, on the initial stage of BBN induced rat urinary bladder carcinogenesis. MATERIALS AND METHODS: Seven-week-old, male Wistar rats were used. The rats were divided into four groups. All groups except control were allowed free access to the drinking water containing 0.05% BBN. Groups Lz40 (n = 5) and Lz80 (n = 5) were administered the liarozole solution, twice daily by gavage (40 mg/kg/day and 80 mg/kg/day, respectively). Group BBN (n = 5) was given no liarozole. The control group (n = 4) received no carcinogen. At 9 weeks after the start of the experiment, all rats were killed by ether anesthesia and their urinary bladders were taken for evaluation. The urinary bladders were fixed in 10% buffered formalin, embedded in paraffin, sectioned, and immunohistochemical staining using anti-proliferative cell nuclear antigen (PCNA) antibody was performed by the avidin-biotin-peroxidase complex (ABC) method. We calculated the PCNA positive rate and compared among the four groups. RESULTS: The PCNA positive rate of group BBN was 23.5 +/- 3.7%. Compared with group BBN, the PCNA positive rate of groups Lz40 and Lz80 were statistically less (16.4 +/- 4.3% and 9.8 +/- 2.6%, respectively). Furthermore, the PCNA positive rate of group Lz80 was statistically less than that of group Lz40. CONCLUSION: The results indicate that liarozole may inhibit the activity of cell proliferation in the initial stage of BBN-induced rat urinary bladder carcinogenesis and may be dose-dependent.

Animals↗
PubMed1990

[Ultrasound cystometry with reference to urinary bladder form and bladder filling].

In 103 patients we performed sonographic determination of the volume (V) of the urinary bladder, being the product of the transversal (q), ventrodorsal (t) and craniocaudal (h) diameters, and compared this with the excreted volumes of urine. Depending on the shape and filling of the bladder we found different correlations from which it was possible to calculate three correction factors (F) for the formula V = (q x t x h) x F:F = 1.25 for volumes less than 150 ml; F = 0.9 for spherically sagittal section and volumes greater than 150 ml. The factor 0.5 given in most textbooks on sonography will in the majority of cases result in underestimating the urinary bladder volumes. Accurate sonocystometry taking the shape and filling into consideration is imperative for performing follow-up and treatment monitoring in neurogenic disturbances of voiding of the bladder or occlusive disturbances of flow in the region of the urethra.

Female↗
PubMedDate not supplied

Induction of transitional cell hyperplasia in the urinary bladder and aberrant crypt foci in the colon of rats treated with individual and a mixture of drinking water disinfection by-products.

Cancer of the urinary bladder and colon are significant human health concerns. Epidemiological studies have suggested a correlation between these cancers and the chronic consumption of chlorinated surface water containing disinfection by-products (DBPs). The present study was designed to determine if exposure to DBPs would cause preneoplastic or neoplastic lesions in the urinary bladder and colon of rats, and what effect a mixture of DBPs would have on these lesions. Male and female Eker rats were treated via drinking water with low and high concentrations of potassium bromate, 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), chloroform, or bromodichloromethane individually or in a mixture for 10 months. The urinary bladders and colons were examined for the presence of preneoplastic lesions. Cell proliferation in the urothelium was examined using immunohistochemical staining for bromodeoxyuridine. Aberrant crypt foci (ACF), as well as the number of individual crypts in each ACF, were identified and counted microscopically after staining with 0.2% methylene blue. Colon crypt cell proliferation and mitotic index were determined using immunohistochemical staining for proliferating cell nuclear antigen. Labeling indexes for the urinary bladder and colon were calculated based on the percentage of positively labeled cells. Treatment with the high dose of MX caused transitional epithelial hyperplasia and cell proliferation in the rat urinary bladder, and this effect was diminished in the high dose mixture animals. Treatment with 4 individual DBPs, as well as a mixture of them, caused the development of ACF, the putative preneoplastic lesion of colon cancer.

Animals↗
PubMed1976

[The application of Actihaemyl in chronically inflamed and dystrophic urinary bladder (author's transl)].

The effect of automated continuous irrigation treatment with Actihaemyl on bacterial growth in the infected urinary bladder was tested using an experimental model. The result was that instillation alone of this preparation promoted growth of Escherichia coli, Proteus mirabilis, and Pseudomonas aeruginosa in the infected bladder. With simultaneous application of Framycetinsulfate or Kanamycin the growth of Pr. mirabilis and Ps. aeruginosa was totally suppressed in the "urine", and the growth of E. coli extensively low. At the same time there was a clear reduction in the bacterial count in the coagulum that served as a substitute bladder wall. Thus a urinary tract infection is a contraindication for local treatment with Actihaemyl of a tropically disturbed urinary bladder inasmuch as an effective antibiotic is not added to the instillate. With the latter combination, however, a therapeutic trial is justified in chronic, inflammatory, dystrophic bladders.

Actihaemyl↗
PubMed1985

Androgen metabolism in tissue recombinants composed of adult urinary bladder epithelium and urogenital sinus mesenchyme.

Epithelium of the adult mouse urinary bladder (BLE) was experimentally combined with mesenchyme of the urogenital sinus (UGM) and grown in intact male hosts to produce prostate-like glandular structures. To determine the extent to which the BLE is altered in a functional sense by inductive influences from UGM, investigations into the in vitro metabolism of tritiated testosterone (T) were undertaken. An isocratic high performance liquid chromatographic (HPLC) method was developed in order to separate the metabolites of T in mouse bladder, prostate and UGM + BLE tissue recombinants. Using a C-18 reversed phase column and a tetrahydrofuran (20): methanol (40): H2O (40) mobile phase, efficient and rapid separation of T, dihydrotestosterone, 3 alpha-androstanediol, androstenedione, androstanedione and androsterone was achieved. The identities of the radiolabeled T metabolites were confirmed by recrystallization to constant specific activity. The results of the present study revealed that tissue recombinants expressed testosterone metabolic profiles only partially toward that of the adult prostate. For example, percentage formation of 5 alpha-androstanedione, 3 alpha-androstanediol and unknown polar metabolites in the UGM + BLE resembled the prostate and differed significantly from the urinary bladder. Conversely, formation of the 3 beta-androstanediol and androsterone from testosterone resembled the urinary bladder and differed from the formation of these metabolites in the prostate. These results suggest that in contrast to histomorphology, androgen-induced DNA synthesis, androgen receptor binding activity and total tissue two-dimensional gel electrophoretic protein profiles, androgen metabolic profiles in the tissue recombinants showed only partial transformation into prostatic phenotypes. Analysis of steroid-metabolic profiles, therefore, may represent an exquisite and sensitive method to assess gene expression in various hormone-responsive target tissues.

Androgens↗