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Dose- and time-response studies of sodium o-phenylphenate urinary bladder carcinogenicity in rats.

Dose- and time-response studies of urinary bladder carcinogenesis due to orally administered sodium o-phenylphenate (OPP-Na) were performed using 5-week-old male Fischer 344 rats given diets containing 0 (control), 2500, 5000, 10,000, 15,000 or 20,000 ppm OPP-Na for 104 weeks and fed basal diets until 112 weeks (experiment 1). In addition, rats received diets containing 20,000 ppm OPP-Na for 0 (control), 12, 24, 52 or 104 weeks and were killed at week 112 (experiment 2). In experiment 1, the transitional cell carcinoma (TCC) was the major tumor type in the urinary bladder, and the dose-response curve was steep with many tumors occurring at the high doses of 15,000 and 20,000 ppm. The virtually safe dose at a risk level of 10(-6) for TCCs and papillomas was estimated to be 144 ppm by the Weibull model, a high value similar to that for sodium saccharin. In experiment 2, a few TCCs developed after 24 weeks of treatment, but the time-response curve was also steep with the majority of lesions occurring after longer exposure periods. Based on the observed steepness in dose- and time-responses, any implied cancer risk of OPP-Na at the low doses of interest to man must be considered to be very small.

Agrochemicals↗

Autonomic innervation of rabbit urinary bladder following estrogen administration.

The effects of estrogen administration on the autonomic innervation of the rabbit urinary bladder were studied. Immature female white rabbits were injected twice daily with estrogen (150 microgram./Kg.) for four consecutive days. Control animals received injections of vehicle alone. The adrenergic innervation was identified using the glyoxalic acid method of catecholamine histofluorescence. The cholinergic innervation was visualized utilizing specific acetylcholinesterase staining. Additionally, the effect of estrogen administration on the response of smooth muscle strips of urinary bladder to specific autonomic agonists was determined. Estrogen administration induced a moderate increase in the adrenergic innervation of the rabbit bladder detrusor, whereas no change could be observed in the cholinergic innervation. It should be noted, however, that whereas the adrenergic innervation in the bladder of the control animal was sparse, the cholinergic innervation in the bladder body was quite dense. Estrogen induced a marked increase in the response to alpha-adrenergic (methoxamine) and muscarinic cholinergic (bethanechol) agonists. No alterations were noted in the response to beta-adrenergic agonists (isoproterenol). These findings indicate that the urinary bladder responds as a target organ for estrogen-induced alterations in autonomic innervation.

Animals↗

Immunohistochemical demonstration of carcinoembryonic antigen (CEA) and its correlation with grading and staging on tissue sections of urinary bladder carcinomas.

In 150 transitional cell carcinomas (TCC) of the urinary bladder, 50 each of Grades 1, 2, and 3, the content of carcinoembryonic antigen (CEA) was examined immunocytochemically and correlated to grading and staging. Fifty-seven percent of the TCC contained CEA-positive tumor cells. Their distribution in tumor tissue is described. They were found in 24% of Grade 1 cases, in 72% of Grade 2 carcinomas, and in 76% of Grade 3 tumors. None of the Grade 1 cases contained more than 10% CEA-positive cells, whereas 34% and 40% of the Grade 2 and 3 tumors, respectively, revealed more than 10% CEA-positive tumor cells. According to the correlation found between grading and staging, the percentage of TCC containing CEA-positive tumor cells was 34% in pTA, 59% in pT1, and 80% in pT2/3 tumors. The results show a correlation between CEA content of tumor tissue and histopathologic malignancy in TCC of urinary bladder.

Anaplasia↗

Comparative evaluation of the nuclear matrix protein, fibronectin, urinary bladder cancer antigen and voided urine cytology in the detection of bladder tumors.

PURPOSE: We evaluate the diagnostic efficacy of nuclear matrix protein-22 (NMP22, Matritech, Newton, Massachusetts), fibronectin and urinary bladder cancer antigen (UBC, IDL Biotech, Borlange, Sweden) compared with voided urine cytology in the detection of bladder cancer. MATERIALS AND METHODS: A total of 168 patients provided a single voided urine sample for NMP22, fibronectin an ideal monoclonal for urinary bladder cancer and cytology before cystoscopy. Cystoscopy was done for all patients as the reference standard for identification of bladder cancer. Biopsy of any suspicious lesion was performed for histopathological examination. Of the 168 cases 100 were histologically diagnosed as bladder cancer, whereas the remaining 68 had benign urological disorders. A group of 47 healthy volunteers were also enrolled in this study. Voided urine was evaluated by NMP22, fibronectin and UBC, and their values were expressed relative to mg. creatinine. RESULTS: The optimal threshold values for NMP22, fibronectin and UBC were calculated by receiver operator characteristics curves as 27 units per mg. creatinine, 198 mg./mg. creatinine and 13 ng./mg. creatinine, respectively. The levels and positive rates of the 3 parameters were significantly higher in the malignant group compared to either the benign group or normal controls. Of the entire group NMP22, fibronectin and UBC were positive in 93.2%, 91% and 68.2%, respectively in bladder cancer cases with positive cytology. Moreover, these positive rates were significantly higher in bilharzial bladder cancer cases (58.8%, 67.5%, 58.8%, respectively) compared to nonbilharzial cases (35.6%, 36.3%, 31.1%). Overall sensitivity and specificity were 85% and 91.3% for NMP22, 83% and 82.6% for fibronectin, 67% and 80.8% for UBC and 44% and 100% for voided urine cytology. Combined sensitivity of voided urine cytology with the 3 biomarkers together was higher than either combined sensitivity of voided urine cytology with 1 of the biomarkers or than that of the biomarker alone. CONCLUSIONS: Our data indicate that NMP22 and fibronectin had superior sensitivities compared to UBC and voided urine cytology, while NMP22 and voided urine cytology had the highest specificities. The combined use of markers increased the sensitivity of cytology from 44% to 95.3%. The higher sensitivities of markers in bilharzial than nonbilharzial bladder cancer highlight their clinical use in screening patients with urinary bilharziasis.

Adult↗

Effect of alpha 1-adrenoceptor antagonists on urinary bladder function in urethane-anesthetized rats.

1. We investigated the effects of selective alpha 1-adrenoceptor antagonists on rhythmic bladder contraction and cystometrograms as representative of urinary bladder function in urethane-anesthetized rats. 2. The selective alpha 1-adrenoceptor antagonists tamsulosin (0.03-3 micrograms/kg IV), prazosin (0.03-3 micrograms/ kg IV) and bunazosin (0.03-3 micrograms/kg IV) exerted little effect on the amplitude and frequency of rhythmic bladder contraction in anesthetized rats. In contrast, the antipollakiuria agent flavoxate (5 and 10 mg/kg IV) induced a dose-dependent disappearance in frequency without affecting the amplitude of the contractions. 3. Tamsulosin (1 and 3 micrograms/kg IV), prazosin (1 and 3 micrograms/kg IV), and bunazosin (1 and 3 micrograms/kg IV) exerted no effect on the cystometrogram, either. However, flavoxate (5 and 10 mg/kg IV) raised the micturition threshold pressure and prolonged the time to micturition. 4. These results suggest that the alpha 1-adrenoceptor plays little role in urinary bladder contraction in anesthetized rats.

Adrenergic alpha-Antagonists↗

Power Doppler ultrasound imaging for quantification of urinary bladder neck blood flow changes.

This study was designed to evaluate power Doppler imaging for assessment of urinary bladder neck blood flow in comparison with laser Doppler flowmetry (LDF) in an animal model. Transrectal power Doppler ultrasound (US) and LDF of the urinary bladder neck were performed in three anesthetized pigs during comparative cystometry. Normal saline (NaCl) was used for the first run, followed by a second run with 0.2 mol/L potassium chloride (KCl). Standardized sonographic equipment settings (Acuson Sequoia 512); MountainView, CA) were used for power Doppler imaging. Computer-assisted calculation of color pixel density (CPD) of power Doppler images was performed using Scion Image) software image analysis. Tissue perfusion units (TPU) were measured using a BLF21 laser Doppler flowmeter (Transonic Systems Inc., Ithaca, NY, USA). The power Doppler results were compared with the findings obtained by LDF. NaCl filling resulted in a mean CPD increase at the bladder neck from 18.65 (+/- 1.78) at empty bladder to 37.8 (+/- 1.84) at 100 mL and to 88.32 (+/- 1.35) at full bladder capacity (C(max)) of 270 mL, respectively. With KCl filling, a mean CPD increase from 18.65 (+/- 1.78) to 59.63 (+/- 0.5) at 100 mL and 110.82 (+/- 2.98) at full bladder capacity (270 mL) was observed. The CPD increase was significantly higher for KCl than with NaCl (p < 0.001). With NaCl filling, bladder neck blood flow increased from 22 TPU (empty) to 46 TPU (100 mL) and 62.5 TPU at C(max), compared to 22 TPU, 50 TPU and 102.5 TPU with KCl. CPD and TPU measurements showed a strong correlation at p = 0.01. In conclusion, transrectal power Doppler US image quantification is a feasible and accurate method for assessing blood flow changes in the urinary bladder neck.

Animals↗

The natural history of nephrogenic adenoma of the urinary bladder.

The nephrogenic adenoma is a peculiar lesion of the urinary bladder characterized partly by villous and partly by gland-like structures. The two layered surface epithelium consists of an eosinophilic cell layer, which covers a clear cell layer, the latter resting upon a delicate basal layer. The clear cells disappear when approaching the tip of the villi. There exists a 200 micron wide zone of transition between the urinary bladder epithelium and that of the neprogenic adenoma. At the base of the villi there are scattered nodules of gland-like structures lined either by eosinophilic cells or by clear cells. These epithelial cells are derived from the corresponding surface epithelial cells from which they had separated by active downwards growth.

Adenoma↗

[Tuberculosis of the urinary bladder: diagnosis and treatment].

Tuberculosis of the urinary bladder (UB) is registered in 10-45.6% patients with urogenital tuberculosis. It is a severe incapacitating complication of kidney tuberculosis which significantly lowers quality of life. The results of the standard therapy of 76 patients with tuberculous cystitis are analysed. UB tuberculosis is diagnosed more often in women, outcomes of their treatment are worse. Twenty six patients with UB tuberculosis at the stage of overactive bladder received polychemotherapy and adjuvant trospium. After 3 months urination frequency decreased 4.3 times, on the average; UB volume increased 4.7 times, on the average. Complications were not registered.

Adolescent↗

[Detection of apoptosis exposed to 10-hydroxycamptothecin in T24 human urinary bladder cancer cells].

OBJECTIVE: To study whether 10-hydroxycamptothecin (HPT) can induce apoptosis in bladder cancer cell and establish methods for detecting apoptotic cells. METHODS: Human urinary bladder cancer cell line (T24) was exposed in vitro to different concentrations of 10-hydroxycamptothein for various lengths of time. Flow cytometry, Hochest 33258 and Hematoxylin staining were used to determine the induction of apoptosis after use of HPT. DNA gel analysis was also carried out to detect DNA fragmentation. RESULTS: Cell shrinage, nuclear fragmentation and condensed chromosomes showed that apoptosis can be induced by HPT within the concentration of 0.01 - 10 microg/ml. The flow cytometry analysis showed that the percentage of apoptotic cells were related to the concentration and the time of induction. T24 cell line exposed to HPT experienced internucleosomal DNA fragmentation by producing a typical ladder pattern on agarose gel electrophoresis. The detection of minimum exposure time for HPT-induced apoptosis in T24 cells showed that 3 hours of exposure to HPT were enough to trigger internucleosomal DNA fragmentation. Compared to Hochest 33258 staining, Hematoxylin staining was more easy, rapid and accurate to detect apoptosis. CONCLUSIONS: The induction of apoptosis exposed to HPT in T24 human urinary bladder cancer cells is a good model for further studying urinary bladder cancer. Hematoxylin staining is a useful method for detecting apoptosis.

Antineoplastic Agents, Phytogenic↗

Clear cell adenocarcinoma of the urinary bladder inducing acute renal failure.

We report a case of clear cell adenocarcinoma of the urinary bladder. A 59-year-old male was referred to our hospital complaining of oliguria, left lower abdominal pain and loss of appetite. Ultrasonography revealed bilateral hydroureteronephrosis and obstructions at the ureterovesical junction. Magnetic resonance imaging demonstrated an invasive irregular tumor located in the posterior wall of the urinary bladder and urinary infiltration to the left retroperitoneal space. The clinical diagnosis was acute post renal failure due to bilateral ureteral obstructions from an invasive bladder tumor. After we performed bilateral percutaneous nephrostomy, the patient underwent trans urethral biopsy of the bladder tumor, which showed clear cell adenocarcinoma extending from the submucosa to the muscular layer, histopathologically. The patient died of metastatic disease 8 months after diagnosis. To our knowledge, the present case is the 23rd to be reported and demonstrates the shortest survival period in the related literature.

Acute Kidney Injury↗

Leiomyosarcoma in urinary bladder after cyclophosphamide therapy for retinoblastoma and review of bladder sarcomas.

We report an unusual case of a leiomyosarcoma of the urinary bladder after chemotherapy for retinoblastoma and the results of a review of the published reports of bladder sarcomas. A 22-year-old man presented with hematuria and was found to have a mass in his urinary bladder on computed tomography. Transurethral resection of the mass revealed a leiomyosarcoma. The patient underwent radical cystectomy and an ileal conduit was created. The final pathologic examination confirmed high-grade leiomyosarcoma. Prospective randomized combination trials similar to the Intergroup Rhabdomyosarcoma Study in the pediatric population are necessary to better understand and manage these potentially curable sarcomas.

Adult↗

[Influence of ethinyl estradiol sulfonate on the decreased urinary bladder tonus in the menopause].

In 40 women with hypotonic urinary bladder the influence of 17alpha-Athinyl-3-isopropyl-sulfonyloxy-Ostradiol (Athinylöstradiol) (3 X 15 mug/die without weekend) was examined concerning the intravesical pressure; The cystotonometry has been done just before as well in intervalls of 2 months during half year's period of treatment. The authors used the fill-up-cystotonometry of Hartl. The intra-vesical pressure rose significantly by the influence of Athinylöstradiolsulfonat after 2 months treatment already. In comparison to the hypotonic value before treatment there was an average normotonic urinary bladder after application of Athinylöstradiolsulfonat past 4 and 6 months. Incidence on clinical relevance of these results.

Ethinyl Estradiol↗

Central nervous system neurons labelled following the injection of pseudorabies virus into the rat urinary bladder.

Pseudorabies virus was injected into the wall of the urinary bladder and, following incubation times of 2, 3 and 4 days, central nervous tissue was processed immunohistochemically for the presence of virus. Longer incubation times resulted in more extensive spread of the virus. Infected neurons were initially found in the spinal cord (mainly lumbosacral) and, after longer survival times, in raphe nuclei, reticular area, pontine micturition center, locus coeruleus, red nucleus, hypothalamus, preoptic, and cortical areas. These data define a multisynaptic circuit of neurons whose ultimate output influences urinary bladder function.

Administration, Intravesical↗

Involvement of toxicity as an early event in urinary bladder carcinogenesis induced by phenethyl isothiocyanate, benzyl isothiocyanate, and analogues in F344 rats.

Phenethyl isothiocyanate (PEITC)(1) and benzyl isothiocyanate (BITC), naturally occurring constituents of cruciferous vegetables, have been reported to exert inhibitory effects against development of tobacco-specific carcinogen-induced lung tumors and are regarded as promising chemopreventive agents for lung cancer. However, tumor promoting and carcinogenic activities in the rat urinary bladder have been detected in several animal models. The purpose of the present study was to investigate early changes in rat urinary bladder epithelium induced by PEITC and BITC and to explore promotion/carcinogenic mechanisms. In the first experiment, in order to assess acute toxic effects, PEITC or BITC at 0.1% each in the diet were administered to 6-week-old F344 rats for 1, 2, 3, and 7 days and sequential histopathological assessment and urinalysis were performed. In the second and third experiments, structure-activity relationships of PEITC, BITC and 8 other analogues, benzyl isocyanate and benzyl thiocyanate, and phenyl-, alpha-naphthyl-, tert-butyl-, butyl-, methyl-, and ethyl isothiocyanates (ITCs) were explored in a 14-day experiment. In the first experiment, the urinary pH was significantly lowered on day 1 by both PEITC and BITC. Striking features of toxicity, such as marked inflammatory changes characterized by cellular infiltration, apoptosis/single cell necrosis, cytoplasmic vacuolation, erosion, and hemorrhage in the urinary bladder were caused, with peaks apparent on days 2 or 3, respectively. Sequential change in 5-bromo-2'-deoxyuridine (BrdU) labeling indices was in line with the inflammatory response, but the thickness of the urinary bladder epithelium continued to gradually increase up to day 7. In the second and third experiments, simple and papillary or nodular (PN) hyperplasias were observed after 14-days treatment with PEITC, BITC, and phenyl- and butyl ITCs. These results suggest that continuous urinary epithelial cell proliferation due to cytotoxicity may play an important role in the early stage of rat urinary bladder carcinogenesis due to oral administration of ITCs. In addition, hydrophobic activity of ITCs, dependent on the alkyl carbon chain length, might strongly influence the induction of bladder lesions in rats.

Animals↗

Ruptured urinary bladder in a post-parturient cow.

Rupture of the urinary bladder at the time of parturition occurred in a 2 year old Angus cow. Anamnesis included a dystocia followed by a gradual (16 days) onset of anorexia and abdominal distension. Prominent findings on the physical examination were marked dehydration, symmetrical distension of the lower abdomen with ascitic fluid, pneumoperitoneum, absence of rumen contractions, and constipation. Significant laboratory findings were elevations of plasma protein, serum urea nitrogen (SUN) and creatinine, hypochloremia, hyponatremia, hyperkalemia, and metabolic acidosis. The ascitic fluid was present in large quantities (50 liters) and had a markedly elevated urea nitrogen and creatinine concentration when compared to serum values for these substances. Parotid salivary secretion had a reversal of the normal sodium: potassium ratio which was attributed to an increase in aldosterone levels brought about by the hyponatremia. A ventral tear in the urinary bladder was successfully repaired by laparotomy.

Animals↗

A simple method for in vitro studies with rodent urinary bladders.

A method was developed for the in vitro study of rodent urinary bladders. The method consists of everting and distending the urinary bladder in a manner to allow exposure of the luminal surface of the urothelium during in vitro incubation while maintaining the integrity of the structure and morphology of the bladder. A technique for selectively removing the urothelium with SDS buffer for biochemical analysis was described. Incorporation of [3H]leucine into urothelial protein was linear over a 4 h period in the presence of tissue culture medium, but no significant incorporation occurred when urine was used as incubation medium. Autoradiography indicated the [3H]leucine incorporation was almost exclusively in the urothelial cells with essentially no incorporation by cells below the tunica propria.

Animals↗

Promoting effects of sodium L-ascorbate on two-stage urinary bladder carcinogenesis in rats.

The promoting effect of sodium L-ascorbate on two-stage urinary bladder carcinogenesis in F344 rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine at levels of 0.01 and 0.05% in drinking water was studied. Administration of 5.0% but not of 1.0% sodium L-ascorbate in the diet significantly increased the incidence and number of preneoplastic lesions, papillary or nodular hyperplasia, papilloma, and cancer of the urinary bladder. In groups given 5.0% sodium L-ascorbate, the urine was characterized by an apparent elevation of pH, a decrease of osmolality, and an increase of MgNH4PO4 crystalline. Addition of sodium L-ascorbate to the diet also resulted in increase in the content of ascorbic acid and its metabolite, dehydroascorbic acid, in the urine. These results show that an extremely high dose of sodium L-ascorbate (5.0%) promotes urinary bladder carcinogenesis under the present experimental conditions, while a high dose (1.0%) does not.

Animals↗

Development of growth-associated protein-43 and neurotrophin receptor immunoreactivities in the rat urinary bladder.

Little is known about how the prenatal innervation of the urinary bladder develops. The objective of this study was to define the timing and pattern of innervation of the developing rat bladder using growth-associated protein-43 (GAP-43) immunohistochemistry. In addition, we examined the development of two different classes of transmembrane receptor proteins, the Trk family of tyrosine kinases and neurotrophin receptor p75 immunoreactivities. GAP-43-positive nerves were first detected in the bladder at embryonic day (E) 16. They were growing rapidly to the bladder dome and covered the whole bladder by E18. The density of GAP-43-containing nerves increased in the muscle layer by postnatal day (P) 0. Both Trk receptor-positive and p75 neurotrophin receptor-positive fibers were also first seen at E16. The number of Trk immunoreactive nerves reached a peak at E18, and then decreased over the following days. In contrast, p75-labeled fibers were abundant at E18-P14. There were few GAP-43 or neurotrophin receptor-positive fibers in the adult. GAP-43 immunohistochemistry provided us with a picture of innervation in the developing rat bladder. Furthermore, the demonstration of neurotrophin receptors positive fibers in the prenatal and early postnatal bladders suggests that neurotrophins may contribute to the development of the peripheral nervous system in the urinary bladder.

Animals↗