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Effects of divalent cations and La3+ on contractility and ecto-ATPase activity in the guinea-pig urinary bladder.

1. Several cations (Ba2+, Cd2+, Co2+, Cu2+, Mn2+, Ni2+, Zn2+ and La3+, all as chloride salts, 1-1000 microM) were tested in the guinea-pig urinary bladder for their ability to: (i) modify contractile responses to electrical field stimulation (EFS), ATP, alpha,beta-methylene ATP (alpha,beta-meATP), carbachol (CCh), and KCl; (ii) affect ecto-ATPase activity. 2. Ba2+ (10-1000 microM) concentration-dependently potentiated contractile responses evoked by EFS (4-16 Hz), ATP (100 microM), alpha,beta-meATP (1 microM), CCh (0.5 microM), and KCl (30 mM). Ni2+ at concentrations of 1-100 microM also potentiated contractility of the urinary bladder, but at concentrations tested its effect was not concentration-dependent. Cu2+ at a concentration of 10 microM and Cd2+ at a concentration of 1 microM potentiated responses to all stimuli, except KCl. Ni2+ at a concentration of 1000 microM and Cd2+ at a concentration of 100 microM inhibited contractions evoked by all stimuli, and at a concentration of 1000 microM Cd2+ abolished any contractions. Responses to ATP and alpha,beta-meATP were selectively inhibited by Cu2+, Zn2+ or La3+, each at a concentration of 1 mM. 3. Cu2+, Ni2+, Zn2+ and La3+ (100-1000 microM) concentration-dependently inhibited ecto-ATPase activity in the urinary bladder smooth muscle preparations, while Ba2+ and Mn2+ were without effect, and Cd2+ and Co2+ caused significant inhibition only at a concentration of 1000 microM. 4. There was no correlation between the extent of ecto-ATPase inhibition and the effect on contractile activity of any of the cations. 5. In conclusion, the ability of some divalent cations to inhibit ecto-ATPase activity and to potentiate or inhibit contractile responses in the guinea-pig urinary bladder appear to be independent effects.

Adenosine Triphosphatases↗

Control of the unstable urinary bladder by graded thermoelectric cooling of the spinal cord.

OBJECTIVE: To evaluate local lumbosacral spinal-cord cooling (a novel technique for neuromodulating urinary bladder reflexes) for its feasibility in possible clinical use, by determining the efficacy and the optimum temperature for suppressing reflex urinary incontinence in two rat models of neurogenic urinary bladder instability. MATERIALS AND METHODS: Overactivity of the detrusor muscle was induced by inflammation of the urinary bladder in a group of rats. A second group of rats was examined 6 weeks after complete midthoracic spinal cord transection, when all animals had developed neurogenic bladder hyper-reflexia. The intravesical pressure, urethral pressure and electromyographic (EMG) activity of the external urethral sphincter (EUS) were recorded simultaneously during repetitive local cooling and re-warming of the dorsal L6/S1 spinal cord segments, using a thermoelectric cooling device. RESULTS: Spinal cord cooling at L6/S1 had no influence on the recorded values at >26 degrees C, but markedly suppressed detrusor contraction frequency at 21- 25 degrees C. Cooling to <20 degrees C completely and reversibly eliminated inflammation-induced bladder contractions in rats with an intact neural axis and significantly reduced the contraction amplitudes (mean reduction 61%) and duration of contractions in spinally transected rats. Cooling simultaneously increased tonic EUS EMG activity and urethral perfusion pressure in both experimental groups, indicating closure of the urethral outlet. Cooling of adjacent spinal cord segments had no influence on bladder and urethral functions. CONCLUSION: Cooling the dorsal spinal cord at the origin of the parasympathetic innervation of the bladder can be used to reversibly suppress bladder instability with simultaneous closure of the urethral outlet. Therefore, local spinal cord cooling, e.g. as an implantable thermoelectric device, may offer a suitable method to treat detrusor overactivity and restore continence.

Animals↗

Metabolic fate of N-butyl-N-(4-hydroxybutyl) nitrosamine and N, N-dibutylnitrosamine in the guinea pig, with reference to their carcinogenic effects on the urinary bladder.

The metabolic fate of two urinary bladder carcinogens, N-butyl-N-(4-hydroxy-butyl) nitrosamine (BBN) and N-N-dibutylnitrosamine (DBN), was studied in the guinea pig, in order to elucidate species differences of response to these N-nitrosamines in this animal species and the rat. Based on the urinary metabolites characterized after oral administration of these compounds, the metabolic pathways of BBN and DBN in the guinea pig were shown to be essentially similar to those in the rat. The principal urinary metabolite of BBN and DBN in the guinea pig, however, was not N-butyl-N-(3-carboxypropyl) nitrosamine (BCPN), as was the case in the rat, but the glucuronic acid conjugate of BBN and that of N-butyl-N-(3-hydroxybutyl) nitrosamine, respectively. The species variation in response to BBN and DBN as bladder carcinogens in these animals is discussed on the basis of the urinary excretion of BCPN.

Animals↗

[Recurrent spontaneous rupture of the urinary bladder: a case report].

The patient was a 67-year-old woman who had undergone radical hysterectomy and postoperative radiotherapy for cervical cancer at the age of 46 years. Spontaneous rupture of the urinary bladder occurred twice in 1997, and conservative treatment was performed on each occasion. She was admitted to our hospital for the third time of spontaneous rupture of the urinary bladder. She underwent bilateral cutaneous ureterostomy because of panperitonitis and paralytic ileus. A review of 11 cases of recurrent rupture of the urinary bladder reported in Japan including the present case revealed that, patients who had been conservatively treated tended to be subject to recurrence. However, the risk of recurrence remains when a partial cystectomy is performed. Therefore, especially in recurrent cases, augmentation cystoplasty or urinary diversion should be considered as the treatment for spontaneous rupture of the urinary bladder due to radiation cystitis.

Aged↗

Spontaneous urinary bladder tumors in DA/Han rats: a feasible model of human bladder cancer.

In a life-span study of virgin DA/Han inbred rats, 53.9% of the males and 14.4% of the females developed spontaneous urinary bladder tumors. A peak incidence was noted between the ages of 25 and 30 months. With the exception of 1 leiomyosarcoma, all neoplasms were of epithelial origin. After the papilloma, the majority of tumors were classified as transitional cell carcinoma of the papillary, solid, or mixed type. Less frequent were unclassified microcarcinoma, squamous cell, adenoid, and undifferentiated carcinomas. A sexual difference was found for almost every tumor type. Of the rats bearing tumors, 3.5% of the males and 64.4% of the females also were affected with urinary bladder stones. Squamous cell and glandular metaplasias of the tumors commonly were observed, and invasive growth into the bladder wall occurred frequently in less-differentiated tumors. Metastases were rare. The DA/Han rat strain is discussed as a suitable animal model for human urinary bladder cancer.

Age Factors↗

Paraganglia of the urinary bladder. An autopsy study.

This is the first full-scale analysis on the paraganglia of the urinary bladder (PUB) by means of histological examination of a large number of autopsy cases. PUB were demonstrated by routine histology in 51.8% of the cases examined. PUB were present in any portion of the urinary bladder as well as in any layer of its mural structure. Immunohistochemistry revealed strong to moderate positivity for chromogranin A and neuron-specific enolase, respectively. A moderate immunoreactivity for S 100 protein was demonstrated in the sustentacular cells of PUB. There has been a statistically significant male preponderance in the incidence of PUB. Contrary to the general consensus, PUB degenerate very slowly throughout the entire lifetime. Middle-aged and elderly subjects suffering from chronic lung diseases exhibit a statistically significant increase in the incidence of PUB, suggesting chronic hypoxemia as a stimulant for the persistence of PUB.

Age Factors↗

Effects of ochratoxin A on DNA repair in cultures of rat hepatocytes and porcine urinary bladder epithelial cells.

In cultured rat hepatocytes the mycotoxin ochratoxin A (OTA) induced unscheduled DNA synthesis (UDS) only in a narrow concentration range. Using a culture medium supplemented with 1% fetal calf serum, at 750 nM OTA a weak induction and at 1 microM OTA a marked induction of DNA repair was observed (15 +/- 11 and 38 +/- 24% cells in repair, respectively). Concentrations > 1 microM OTA were cytotoxic, and <750 nM no induction occurred. In cultures of cells from the urinary bladder (porcine urinary bladder epithelial cells; PUBEC), a target organ of the mycotoxin, OTA induced UDS in a concentration-dependent manner. To inhibit the proliferation of the cultured epithelial cells, which would counteract the detection of DNA repair, epidermal growth factor was omitted and an arginine-deficient medium (ADM) was used. Under these serum-free culture conditions the amount of cells undergoing DNA repair in PUBEC control cultures was approximately 7 +/- 4%, a value also comparable to those of control cultures of rat hepatocytes. At concentrations between 250 nM and 1 microM OTA a concentration-dependent increase of cells in repair was observed. Above 1 microM OTA was cytotoxic. At this concentration a maximum of approximately 61 +/- 9% of the cells undergo DNA repair. This amount is comparable to control cultures incubated with 5 or 10 mM ethylmethane-sulphonate (EMS) (49 +/- 9 and 69 +/- 10% cells in repair, respectively), used as a positive control. These results show that in cultured rat hepatocytes induction of UDS is relatively weak whereas in urothelial cells this effect was significant. Whether this effect is due to OTA metabolites formed locally in the urothelium cannot be excluded since PUBEC have been shown to be able to metabolize xenobiotics independently from the liver.

Animals↗

Steroid-induced protein synthesis in giant-toad (Bufo marinus) urinary bladders. Correlation with natriferic activity.

We have identified a group of proteins (Mr approximately 70 000-80 000; pI approximately 5.5-6.0) in giant-toad (Bufo marinus) urinary bladders whose synthesis appears to be related to aldosterone-stimulated Na+ transport. Spironolactone, a specific mineralocorticoid antagonist in renal epithelia, inhibits the synthesis of these proteins as well as the natriferic effect of the hormone. Since a variety of other steroids (some of which are traditionally considered to be glucocorticoids) also stimulate Na+ transport in toad urinary bladders, we examined whether their natriferic activity was expressed in a fashion similar to that of aldosterone. Short-circuit current was used to measure Na+ transport, and epithelial-cell protein synthesis was detected with high-resolution two-dimensional polyacrylamide-gel electrophoresis and autoradiography. At a concentration of approximately 100 nM, dexamethasone, corticosterone and aldosterone were equinatriferic. Dexamethasone and aldosterone had identical dose-response curves, maximal and half-maximal activity being evident at concentrations of approximately 100 nM and 10 nM respectively. In contrast, at a concentration of approximately 10 nM, corticosterone had no effect on Na+ transport. The natriferic activities of these three steroids correlate with their known affinities for the putative mineralocorticoid receptor in toad urinary bladders. Natriferic concentrations of dexamethasone and corticosterone (140 nM) induced the synthesis of proteins with characteristics identical with those induced by aldosterone. Spironolactone, at an antagonist/agonist ratio of 2000:1, inhibited steroid-induced Na+ transport and the synthesis of these proteins. Thus it appears that all natriferic steroids share a common mechanism of action in toad urinary bladders. Natriferic activity can be correlated not only with relative steroid-receptor affinity but also with the induction of a specific group of epithelial-cell proteins.

Aldosterone↗

Promoting effect of trisodium nitrilotriacetate monohydrate on urinary bladder carcinogenesis in rats.

The promoting effect of trisodium nitrilotriacetate monohydrate (Na3NTA X H2O) on two-stage urinary bladder carcinogenesis in F344 rats initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) at levels of 0.01 and 0.05% was investigated. Administration of 2.0% Na3NTA X H2O significantly increased both the incidence and the number per 10 cm of basement membrane of preneoplastic lesions and papillomas of the urinary bladder in rats pretreated with 0.05% BBN. This result shows that Na3NTA X H2O has weak promoting activity in urinary bladder carcinogenesis.

Acetates↗

Saturable urea transport pathway across the urinary bladder of Bufo viridis and salt acclimation.

Urea fluxes across the urinary bladder of Bufo viridis were studied in vitro after modification of the mounting technique. The fluxes increased as a function of the bath urea concentration, saturating near 200 mmol/l. The apparent Km was 88 mmol/l in the bladders from tapwater-acclimated toads, and 107 mmol/l in toads acclimated to 500 mOsm NaCl. The Vmax which was 300 mumol.h-1.cm-2 at room temperature in bladders from tapwater acclimation, changed to more than 1500 mumol.h-1.cm-2 upon salt acclimation. It is suggested that urea movement across the urinary bladder of this species occurs by facilitated diffusion and that salt acclimation induces an increase in the density of this pathway, but not of its characteristics (Km).

Acclimatization↗

Urologic complications of placenta percreta invading the urinary bladder: a case report and review of the literature.

INTRODUCTION: Placenta percreta invading the urinary bladder may cause hemorrhagic shock, hematuria and urologic complications at parturition. This retrospective survey of 54 patients reviews maternal characteristics, presentations, urologic complications, and management. METHODS: The first reported case of placenta percreta with urinary bladder invasion in Hawaii is presented. Medline search and literature review identified an additional 53 patients. A meta-analysis of all 54 cases was performed. RESULTS: Hematuria was present initially in 31% (17/54) patients. Of these, 9 of 17 required transfusion support. A preoperative diagnosis was established by ultrasound or MRI in 33% of patients. Cystoscopy was performed in 12 patients and did not make a preoperative diagnosis in any patient. 39 urologic complications included bladder laceration 26%, urinary fistula 13%, gross hematuria 9%, ureteral transection 6%, and small capacity bladder 4%. Partial cystectomy was performed in 44% (24/54). Three maternal deaths and 14 fetal deaths occurred. Only 1 patient subsequently had a delivery. CONCLUSION: Readily identifiable risk factors by history are important to suggest placenta percreta in pregnant patients with gross hematuria. Ultrasound and/or MRI can establish a preoperative diagnosis. Cystoscopy did not identify any patient preoperatively. Partial cystectomy is commonly required for extensive or deep bladder invasion.

Adult↗

[A case of primary signet ring cell carcinoma in urinary bladder].

A case of primary signet ring cell carcinoma in the urinary bladder in a 50-year-old male is described. The patient with a complaint of urinary incontinence was admitted for invasive bladder carcinoma based on cystoscopic examination. The pathological specimen using transurethral resection-biopsy revealed signet ring cell carcinoma. In the preoperative work up, no obvious metastases were found. Following hospitalization, the patient's course gradually worsened with weight-loss, abdominal fullness and dysuria. The operation for total cystectomy was started, but was interrupted when the peritoneal cavity was found to be fully occupied with massive ascites, invasive lesions into nets and surrounding tissue. He died on November 19, 1986, approximately 7 months after onset of symptoms. An autopsy proved that the tumor which was pathologically identified as signet ring cell carcinoma, originated from the urinary bladder invading the perivesical tissues, and also into the intraabdominal space. We found 34 cases in the literature, originating from the urinary bladder. This case is considered to be the 35th. In conclusion, rapid total cystectomy following an early and definite diagnosis is the only procedure to treat such tumors.

Adenocarcinoma, Mucinous↗

Urinary bladder and hindlimb afferent input inhibits activity of primate T2-T5 spinothalamic tract neurons.

1. Extracellular recordings were made from 41 spinothalamic tract (STT) neurons on the left side of the T2-T5 spinal segments of 20 monkeys (Macaca fascicularis) anesthetized with alpha-chloralose. Manipulation of the left triceps-chest region and electrical stimulation of cardiopulmonary sympathetic afferent fibers excited these cells. 2. Isotonic urinary bladder distensions (UBD) to pressures between 20 and 80 cmH2O reduced the spontaneous activity in 33 of 41 cells. Cell activity was significantly reduced by UBD at 20 cmH2O. Distensions to 40, 60, and 80 cmH2O produced progressively greater reductions in spontaneous discharge. Activity was decreased throughout distension in 29 cells (tonic inhibition) and at the onset of distension in 3 neurons (phasic inhibition). In one cell, inhibition followed a brief excitation at the onset of distension (phasic excitation-tonic inhibition). Spontaneous bladder contractions also inhibited STT cell activity. 3. Inhibition by UBD was observed in STT cells characterized as wide dynamic range, high threshold, and high threshold inhibitory. No correlation existed between cell type or laminar location and inhibition by urinary bladder distension. Cells excited by cardiopulmonary sympathetic afferent A delta- and C-fibers had a significantly greater tendency to be inhibited by UBD (17 of 18) than cells activated by A delta- but not C-fibers (13 of 20). 4. Urinary bladder distension and pinch of the hindlimbs also reduced activity of STT cells excited by input from cardiopulmonary sympathetic afferents and from the proximal forelimb. 5. Urinary bladder distension to 40, 60, or 80 cmH2O produced a greater absolute but smaller relative reduction in the firing frequency of STT cells as spontaneous activity increased. Thus the magnitude of this inhibitory effect may depend on whether the inhibitory effect is measured as an absolute or relative change in cell activity. 6. Convergent inhibitory input from somatic regions also was observed. Noxious pinch of the hamstring region of the right hindlimb decreased activity in 32 of 39 cells. Left hindlimb pinch inhibited 21 of 38 cells, and 15 of 29 cells were inhibited by right triceps pinch. 7. Convergent inhibitory input from the hamstring region of the hindlimbs and from the urinary bladder to upper thoracic STT cells may be important for coding the intensity and location of noxious visceral and somatic stimuli and for organizing the appropriate sequence of motor responses when multiple noxious stimuli are present.

Action Potentials↗

Protection by indomethacin and aspirin against genotoxicity of ochratoxin A, particularly in the urinary bladder and kidney.

Ochratoxin A (OTA) is a ubiquitous nephrotoxic mycotoxin which was shown to be carcinogenic to laboratory animals and may be responsible for kidney pelvis, ureter and urinary bladder tumors associated with Balkan endemic nephropathy in man. Previous evidence from this laboratory demonstrated that OTA exposure results in adduct formation on kidney, testicles, liver and spleen DNA. We show in this study that after a single oral administration of OTA to mice (2 mg/kg body weight) a high level of DNA adducts (150 per 10(9) nucleotides) is also detected in the urinary bladder. The metabolic pathway of OTA leading to genotoxic compounds is not yet known. We demonstrate here that two inhibitors of the prostaglandin H synthase, indomethacin and aspirin, administered to mice before OTA treatment, dramatically reduce the amounts of DNA adducts, particularly in the urinary bladder and kidney. This suggests a role of protaglandin H synthase in the metabolism of OTA leading to active metabolites which react with DNA.

Animals↗

[Effect of oxybutynin hydrochloride on isolated smooth muscles (ileum, urinary bladder and urethra)].

Effects of oxybutynin hydrochloride on isolated smooth muscle were investigated in preparations of isolated rabbit bladder body, bladder base, collum vesicae and urethra. ACh produced a marked contraction of the preparation from the bladder body and produced no response in the collum vesicae and the urethra; however, NE caused a marked contraction of the preparations from the collum vesicae and the urethra and relaxation in the bladder body. Oxybutynin and papaverine hardly had any effect on these preparations. Effects of oxybutynin on the contractile response of the isolated ileum or urinary bladder of rabbit, guinea pig and rat in comparison with atropine, papaverine, flavoxate and other drugs were investigated. The responsibility of these preparations to ACh were approximately 100 times higher in the ileum than in the urinary bladder. Oxybutynin showed a competitive inhibition to contractile response induced by ACh in the ileum and urinary bladder, whose potency was about 1/7-1/10 that of atropine. In the ileum of rats which were treated with oxybutynin orally at a dose of 1, 10 or 100 mg/kg for 60 days, the response to ACh in the preparations of the animals treated by 100 mg/kg were decreased, but the anticholinergic action in the groups treated with oxybutynin were not significantly different compared with the nontreated or saline treated group. On the other hand, oxybutynin showed a non-competitive inhibition to contractile response induced by Ba2+, Ca2+ and histamine in the guinea pig ileum and Ba2+, high-K+, Ca2+ and ATP in the rabbit urinary bladder. These potencies of oxybutynin were equal or slightly stronger than that of papaverine or flavoxate. However, oxybutynin had no effect on the contraction induced by NE in the rabbit urethra. The above results suggest that oxybutynin has atropine-like anticholinergic action and direct muscle relaxant action evidenced by non-competitive inhibition to contractile response induced by several agonists.

Acetylcholine↗

Effect of cyclophosphamide on rat urinary bladder epithelium treated wtih N-butyl-N-(4-hydroxybutyl)nitrosamine.

The effect of cyclophosphamide (CP) on the urinary bladder epithelium of rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was examined histologically to detect preneoplastic papillary or nodular hyperplasia. The urinary bladder epithelium of rats injected intraperitoneally with 40 or 80 mg/kg body weight of CP after treatment with 0.025% BBN for 2 weeks showed extensive epithelial erosion and then simple, or papillary or nodular hyperplasia, but this soon almost disappeared. In contrast, rats given BBN alone showed papillary or nodular hyperplasia later. These findings indicate that epithelial damage by CP inhibited the early neoplastic process of BBN.

Animals↗

[Grading and staging of urinary bladder carcinomas (author's transl)].

In a retrospective study, staging and grading of 2085 primary and recurrent urinary bladder carcinomas were determined according to WHO and UICC rules. Of the carcinomas 51% were papillary, 23% solid and 26% partly papillary and partly solid. 46.2% of carcinomas were correspondent to malignancy grade I, 37.7% to grade II and 16.1% to grade III. The depth of invasion was the greater the less the degree of differentiation. The uncorrected recurrence rate of carcinoma was 14.9%, 28% of the recurrences showed an increase in malignancy grade and (or) depth of invasion. The recurrence rate fell within the first three years from 76.8% to 8.2%. In addition, there was a high degree of coincidence between carcinoma grade III and severe urothelial dysplasia. The diagnosis of severe dysplasia is an indication for frequent cystoscopic and bioptic checks. Since the biological significance of urinary bladder carcinoma depends not only on the degree of malignancy but also on the depth of invasion and the readiness of carcinoma towards invasion, it is necessary for successful prospective studies, designed to evaluate the course of urinary bladder carcinoma and their therapeutic response, to incorporate exact staging and grading.

Adult↗