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Effects of drugs used in the therapy of detrusor hyperactivity on the volume-induced contractions of the rat urinary bladder.

In this study we examined the effects of the drugs most commonly utilized in the therapy of overactive detrusor, on the volume-induced contractions of rat urinary bladder. Anticholinergics such as propantheline bromide and emepronium bromide, as well as oxybutynin decreased the amplitude of the voiding contractions after intravenous (i.v.) administration in a dose-dependent way. These anticholinergics, on the other hand, generally increased the frequency of the contractions. Nifedipine dose-dependently reduced the amplitude of the contractions. Flavoxate induced a dose-related decrease in the frequency without effects on the amplitude of the peaks. Its main metabolite 3-methylflavone-8-carboxylic acid (MFCA) was inactive after i.v. administration. Terodiline was active on the amplitude and apparently on the frequency of the voiding contractions. The alpha-adrenoceptor antagonist prazosin, as well as indomethacin, inhibited only the frequency of the voiding contractions. All the drugs active in reducing the frequency of the voiding contractions after i.v. administration, proved effective also after intracerebroventricular (i.c.v.) injection. The model of the volume-induced contractions of rat urinary bladder, seems to be a useful tool to evaluate in vivo the effects of a compound on the bladder, allowing the possibility of distinguishing among antimuscarinics and calcium antagonists, which peripherally decrease bladder contractility, and other drugs inducing a decrease in the frequency of the voiding reflex acting on the micturition centre(s) in the central nervous system (CNS).

Animals↗

Enhancement of urinary bladder carcinogenesis by combined treatment with benzyl isothiocyanate and N-butyl-N-(4-hydroxybutyl)nitrosamine in rats after initiation.

Previously we reported that benzyl isothiocyanate (BITC) strongly enhanced rat urinary bladder carcinogenesis after initiation with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), while potently inhibiting BBN-induction of lesions when given simultaneously with the carcinogen. In the present experiment, the effects of simultaneous treatment with BITC and low-dose BBN on the post-initiation period of rat urinary bladder carcinogenesis were examined. After treatment with 500 ppm BBN for 4 weeks for initiation, groups of 20, 6-week-old, F344 male rats were given 25 ppm BBN alone, basal diet alone, or 100 or 1000 ppm BITC in the diet together with or without 25 ppm BBN in their drinking water for 36 weeks and then killed for autopsy. Further groups consisting of 10 rats each were similarly given BITC or the basal diet together with or without 25 ppm BBN, without initiation treatment. In the initiated groups receiving subsequent BBN exposure, papillary and nodular hyperplasia, dysplasia and carcinoma incidences were significantly increased, and they were further increased by the combined treatment with 100 and 1000 ppm BITC in a dose-dependent manner. In the non-initiation groups, carcinomas were only observed in a single rat in each of the BBN-treated control and BBN/BITC 100 ppm treatment groups. The results indicate that simultaneous treatment with BITC and a low dose of BBN does not inhibit, but rather enhances rat urinary bladder carcinogenesis after appropriate initiation, and further suggest that BITC may be a human risk factor, at least in high-risk populations.

Animals↗

[Small cell carcinoma of the urinary bladder: a case report].

We report a case of primary small cell carcinoma of the urinary bladder. A 74-year-old woman was referred to our hospital because of pollakiuria. Cystoscopy showed a papillary tumor. We operated transurethral resection of the bladder tumor (TUR-Bt). Histopathological finding was transitional cell carcinoma (TCC), grade3, pT1 containing pTis. About six months later, tumor recurred to the bladder. Pathologic diagnosis was TCC in part and most was small cell carcinoma. Pelvic magnetic resonance imaging revealed a huge mass lesion with extravesical extension in the urinary bladder, and computed tomography scan showed external iliac lympho node metastasis. The rapid rise of a tumor maker NSE and pro-GRP were remarkable. It was diagnosed as a rapid advance of small cell carcinoma. We performed pelvic radiotherapy, and chemotherapy using carboplatin (CBDCA) and etoposide (VP-16). However 14 months after it had left hospital, computed tomography showed paraaortic lympho node metastasis. The patient died due to rapidly progressive disease.

Aged↗

Acute alterations in biochemistry, morphology and contractility of rat isolated urinary bladder via increased intra-abdominal pressure.

OBJECTIVE: To determine the acute effects of increased intra-abdominal pressure (IAP) on the biochemistry, morphology and contractility of the rat isolated urinary bladder using an experimental laparoscopy model. METHODS: We divided 24 adult female Sprague-Dawley rats into three groups. The control group (group I) was not subjected to increased IAP. In groups II and III, IAPs of 10 and 20 mm Hg, respectively, were established by carbon dioxide pneumoperitoneum for 60 min. Thirty minutes after desufflation, the rat urinary bladder dome was removed for in vitro pharmacological investigation, measurement of malondialdehyde (MDA) levels and histopathological examination. Statistical comparisons between groups were performed. RESULTS: Tissue MDA levels in groups II and III were significantly higher than in the control group. In group II, only the lamina propria was significantly damaged. However, the epithelium, lamina propria, and serosa were significantly damaged in group III. Acetylcholine potentiated contractions in both IAP groups. Increased responses to electrical field stimulation in the IAP groups were significant only in group II. CONCLUSIONS: In this experimental model, 10 and 20 mm Hg of IAP induced by pneumoperitoneum increased MDA levels and caused important changes in the morphology and contractile response of the urinary bladder.

Abdominal Cavity↗

Effects of testosterone on neuromuscular transmission in rat isolated urinary bladder.

Testosterone was examined for its effects on neuromuscular transmission in rat and shrew urinary bladder. In isolated preparations of detrusor muscle from sexually immature male rats (8-10 weeks old) at concentrations of 100-300 microM, it inhibited neuromuscular transmission in a concentration-dependent manner and it also inhibited responses to applied carbachol and diadenosine pentaphosphate (Ap(5)A, a P2X receptor agonist). Ethanol (at or above 38 mM), the solvent for testosterone, also caused significant inhibition of neurogenic contractions as well as carbachol- and Ap(5)A-induced contractions. In older, sexually mature male rats (over 16 weeks old), testosterone and ethanol had similar effects to those observed in the young male rat, although both were slightly less potent. In young virgin female rats (8-12 weeks old), testosterone and ethanol inhibited neuromuscular transmission; testosterone was approximately 1000 times more potent than in male rats, with a threshold concentration of 30 nM. In the insectivore, Suncus murinus, testosterone (0.1 microM-1 x mM) caused inhibition of neurogenic and chemogenic responses, but ethanol had no significant effect. Flutamide (50 microM), a genomic testosterone-receptor antagonist, did not inhibit any of the responses to testosterone. It is concluded that testosterone acts predominantly on a postjunctional nongenomic receptor to inhibit urinary bladder detrusor muscle contraction.

Androgen Antagonists↗

Paraganglioma of the urinary bladder: immunohistochemical, ultrastructural, and DNA flow cytometric studies.

Primary paraganglioma arises infrequently in the urinary bladder. We present the clinicopathologic, immunohistochemical, ultrastructural, and DNA flow cytometric findings in three cases (one man and two women). Ages at diagnosis were 19, 35, and 45 years. One female presented with paroxysmal headaches and hypertension that followed urination; the remaining two patients presented with hematuria. Immunohistochemical studies revealed positive reactivity for chromogranin (three patients), met-enkephalin (three), leu-enkephalin (three), vasoactive intestinal polypeptide (two), serotonin (one), and S-100 protein (one; sustentacular cells only). Neurosecretory granules were identified in all cases; in the patient with hypertension, the granules were small with eccentric cores similar to those of adrenal pheochromocytomas. A nondiploid DNA flow cytometric pattern was present in all three patients, an aneuploid pattern was present in two, and a tetraploid pattern was present in one. After diagnosis, one patient was alive without progression at 7 years, one died of an uncertain cause at 5 years, and one suffered multiple recurrences over a 24-year period before developing metastatic disease. While the presence of aneuploidy has been shown to be a predictor of malignant behavior in adrenal pheochromocytomas, our study illustrates that DNA ploidy cannot be used as a diagnostic criterion for malignancy in urinary bladder paraganglioma.

Adult↗

[A case of paraganglioma of the urinary bladder].

Herein we report a case of primary paraganglioma of the urinary bladder. A 21-year-old woman was admitted to an emergency hospital, because of gross hematuria, dysuria and complete urinary retention. Pelvic CT scan and ultrasonic examination revealed a bladder tumor and coagulated blood mass, then she was referred to our clinic for further treatment. On cystoscopy a dark brown lobular tumor was seen on the anterior wall. The bladder tumor was removed by partial cystectomy. The operative specimen measured 6 X 4 X 3 cm and weighed 50 g. Histological examination showed it to be a paraganglioma of the urinary bladder, which was chromaffin positive. Her serum and urinary catecholamine level were within the normal range after operation. She is now ten months postoperative, free from hematuria, and showing no other symptoms or signs of disease including metastasis.

Adult↗

MIRD Pamphlet No. 14 revised: A dynamic urinary bladder model for radiation dose calculations. Task Group of the MIRD Committee, Society of Nuclear Medicine.

UNLABELLED: The constant-volume urinary bladder model in the standard MIRD Pamphlet No. 5 (Revised) phantom has recognized limitations. Various investigators have developed detailed models incorporating more physiologically realistic features, such as expanding bladder contents and residual volume, and variable urinary input rate, initial volume and first void time. We have reviewed these published models and have developed a new model for calculation of radiation absorbed dose to the urinary bladder wall incorporating these aspects. METHODS: The model consists of a spherical source with variable volume to simulate the bladder contents and a wall represented by a spherical shell of constant volume. The wall thickness varies as the source expands or contracts. The model provides for variable urine entry rate (three different hydration states), initial bladder contents volume, residual volume and first void time. The voiding schedule includes an extended nighttime gap during which the urine entry rate is reduced to one-half the daytime rate. RESULTS: Radiation-absorbed dose estimates have been calculated for the bladder wall surface (including photon and electron components) and at several depths in the wall (electron component) for 2-18F-fluoro-2-deoxy-D-glucose, 99mTc-diethylenetriaminepentaacetic acid (DTPA), 99mTc-HEDP, 99mTc-pertechnetate, 99mTc-red blood cells (RBCs), 99mTc-glucoheptonate, 99mTc-mercaptoacetyltriglicine chelator (MAG3), 99mTc-methylene diphosphonate (MDP), 99mTc-hexamethylpropylene amine oxime (HMPAO), 99mTc-human serum albumin (HSA), 99mTc-MIBI (rest and stress), 123I-/124I-/131I-OIH, 123I/131I-NaI, 125I-iothalamate, 111In-DTPA and 89Sr-SrCl. CONCLUSION: The new model tends to give a higher radiation absorbed dose to the bladder wall surface than the previous models. Large initial bladder volumes and higher rates of urine flow into the bladder result in lower bladder wall dose. The optimal first voiding time is from 40 min to 3 hr postadministration, depending on radiopharmaceutical. The data as presented in tabular and graphic form for each compound provide guidance for establishing radiation absorbed dose reduction protocols.

Humans↗

Influence of dose of N-methyl-N-nitrosourea on the induction of urinary bladder cancer in rats.

N-methyl-N-nitrosourea (MNU) was instilled by a urethral catheter into the urinary bladders of female Wistar rats in weekly doses of 0.5 mg for 1, 2, 3 and 4 weeks. At 75 weeks after the initial dose of MNU, the incidences of bladder cancer were 0, 7, 50 and 64% for the total doses of MNU of 0.5, 1.0, 1.5 and 2.0 mg, respectively. Control rats instilled with 0.9% NaCl only for 1--4 weeks did not develop bladder cancer by 75 weeks. Higher doses of MNU of 4.0 and 6.0 mg, given weekly in 0.5 mg amounts for 8 and 12 weeks, respectively, induced a higher incidence (nearly 90%) of urinary bladder cancer in rats at 22--28 weeks. However, it was shown that control rats given 12 weekly installations of solvent only developed a significant number (33%) of bladder cancers by 22--28 weeks.

Animals↗

[The use of human dura in urology, except as a substitute of urinary bladder (author's transl)].

The human dura cannot only be used to replace the urinary bladder wall, but also to replace the capsula fibrosa of the kidney for transposition of aberrant vessels in hydronephrosis, for interposition in vesicovaginal fistula, for suspension of the urethra in stress incontinence and to replace the tunica albuginea of the corpus cavernosum penis after resection of plaque in Peyronie's disease.

Dura Mater↗

Oat cell carcinoma of the urinary bladder with ectopic adrenocorticotropic hormone production.

A case of primary oat cell carcinoma of the urinary bladder with ectopic adrenocorticotropic hormone (ACTH) secretion in a 55-year-old woman is reported. Cystoscopy revealed a large necrotic tumor in the bladder; the tumor was partially electroresected. At autopsy, a large residual tumor infiltrating the wall of the bladder was found. It had metastasized to the lymph nodes, left ovary, liver, spinal canal, bone marrow, and hypophysis. Bilateral adrenocortical hyperplasia was found. Microscopically, the tumor was identical morphologically to oat cell carcinoma, and the cells contained argyrophilic hormone granules and immunohistochemically demonstrable ACTH. Apparently, oat cell carcinomas with endocrinologic activity have not been reported previously in the urinary bladder.

Adrenocorticotropic Hormone↗

Urea transport across urinary bladder and salt acclimation in toad (Bufo viridis).

The fluxes of urea across the urinary bladder of the toad Bufo viridis have been studied under conditions of acclimation to tap water or 500 mosM NaCl solution. The [14C]urea fluxes were measured simultaneously with [3H]inulin to test for nonspecific leakage. The fluxes are quite high (Ktrans = 75 x 10(-7) cm/s at 5 mmol/l urea) and are similar in either the mucosal-to-serosal or the opposite direction. "Summer" rates were five to six times higher than the "winter" rates. Antidiuretic hormone (ADH), theophylline, and forskolin increased the fluxes to variable degrees (two to five times), similar in the two acclimation conditions. Phloretin inhibited the urea fluxes by nearly 50%. 1,3-Dimethylurea and thiourea, but not acetamide, competed with the urea fluxes effectively. The fluxes of urea were not affected by the osmotic water flow, although both responded to ADH. It is concluded that urea transport across the urinary bladder of B. viridis is by facilitated diffusion through a specific pathway independent of water flux. The inhibitory effect of the structural analogues on the urea flux was affected by salt acclimation, whereas most other characteristics did not differ significantly at 5 mmol/l external urea under the two conditions of acclimation.

Adaptation, Physiological↗

[Endometriosis of the ureter and urinary bladder].

Endometriosis is a benign growth of ectopic endometrial mucous membrane which has maintained the histological characteristics and biological reactions of uterine mucous membrane. In only 1-2% of cases does it occur in the urinary system, most commonly in the urinary bladder. Such an endometriosis is often diagnosed very late due both to its commonly asymptomatic course and its rarity. Individual therapy is dependent on the age of the patient, the wish for children and the extent of the growth. For endometriosis covering a large area, surgery is recommended. Methods of choice are laparoscopic bladder resection for the urinary bladder, ureterocystoneostomy using the Psoas hitch for the distal ureter, end to end anastomosis or endoscopic incision for short, proximal cases, and for extended areas, ileum cross-bridge attachment or kidney mobilization using nephropexy.

Endometriosis↗

Initial evaluation of the diagnostic performance of the new urinary bladder cancer antigen test as a tumor marker for transitional cell carcinoma of the bladder.

PURPOSE: We evaluated the diagnostic performance of the new noninvasive bladder cancer test on voided urine samples from patients with transitional cell carcinoma compared to symptomatic and asymptomatic controls. MATERIALS AND METHODS: Urinary bladder cancer antigen was measured in urine from 86 patients with active transitional cell carcinoma of the bladder (group 1), 76 patients free of transitional cell carcinoma as confirmed by cystoscopy at followup (group 2), 25 patients with other benign urological diseases (group 3), 25 patients with other malignant pathological conditions (group 4) and 30 healthy subjects free of urological diseases (group 5). RESULTS: Mean urinary bladder cancer antigen concentrations were 104.84, 4.57, 11.79, 48.87 and 1.38 microg/l, for groups 1 to 5, respectively, which was statistically different (p = 0.00005) except for groups 1 and 4 (p = 0.187). Sensitivity was 87.0% (95% confidence interval 79.2 to 92.7) and specificity was 86.8% (77.1 to 93.5%), and both were optimized by receiver operating characteristics plot analysis at a threshold value of 9.74 microg/l using asymptomatic (group 2) compared to known cancer (group 1) cases. CONCLUSIONS: Urinary bladder cancer antigen might have a role as a potential tumor marker for diagnosing transitional cell carcinoma of the bladder.

Aged↗

Comparative effects of prostaglandin E2 and prostaglandin E3 on water flow and cyclic AMP in the urinary bladder of the frog, Rana pipiens.

Prostaglandins (PGs) modulate osmotic water flow in amphibian urinary bladders. Gas chromatographic analysis of prostaglandin precursors in bladders showed that arachidonic acid represented 13.0 +/- 0.6% and eicosapentaenoic acid 4.3 +/- 0.1% of the total fatty acid content. The effects of PGE2 and PGE3 on basal and arginine vasotocin (AVT) stimulated water flow were compared. Control water flow (1.1 +/- 0.2 mg/min) was increased to 4.6 +/- 0.3 mg/min with AVT (10(-6)M) present. PGE2 (10(-6)M) inhibited both basal and AVT stimulated water flow. In contrast, PGE3 (10(-6)M) stimulated basal water flow and further increased AVT stimulated water flow. Basal adenylate cyclase activity (ACA, 59 +/- 0.3 pmol cyclic AMP/mg protein/10 min) was stimulated by the addition of AVT in the absence or presence of exogenous guanosine 5' triphosphate (GTP, 10(-5)M). Both PGE2 and PGE3 stimulated basal ACA in the absence, but not in the presence of GTP. In the absence of exogenous GTP, PGE2 increased AVT stimulated ACA, whereas PGE3 decreased it. Both prostaglandins inhibited AVT stimulation when GTP was added. The effects of PGE2, PGE3 and AVT on tissue cyclic AMP levels in whole urinary bladders were similar to the effects seen on ACA in the absence of exogenous GTP. The contrasting effects of PGE2 and PGE3 on control water flow appear distinct from their similar effects on ACA. However, PGE2 and PGE3 may regulate AVT stimulation through mechanisms involving cyclic AMP.

Adenylyl Cyclases↗

Strong promoting activity by uracil on urinary bladder carcinogenesis and a possible inhibitory effect on thyroid tumorigenesis in rats initiated with N-methyl-N-nitrosourea.

Uracil has been shown to cause a strong proliferative response in the urinary bladder epithelium of rats and mice through calculus formation and, consequently, acts as a strong promoter in bladder carcinogenesis. In this study, we examined the effect of uracil on two-stage carcinogenesis in various organs using N-methyl-N-nitrosourea (MNU) as the initiator. F344 rats were injected i.p. with MNU twice weekly for 4 weeks and then given diet containing 3.0% uracil for 20 weeks. Uracil induced urinary bladder carcinomas in all rats pretreated with MNU, and it decreased the combined incidence of adenomas and carcinomas in the thyroid. Although not significant, uracil decreased the incidence of adenomas in the lung and increased that of lymphomas of the thymus. A possible influence of a significantly decreased body weight gain caused by uracil treatment on the reduced tumor incidence in the thyroid and lung is discussed. The present data demonstrate the strong promotion activity of uracil for urinary bladder carcinogenesis, and suggest a possible inhibitory effect on thyroid carcinogenesis.

Adenocarcinoma↗

Na(+) and Cl(-) transport by the urinary bladder of the freshwater rainbow trout (Oncorhynchus mykiss).

Freshwater (FW) rainbow trout (Oncorhynchus mykiss) urinary bladders mounted in vitro under symmetrical saline conditions displayed electroneutral active absorption of Na(+) and Cl(-) from the mucosal side; the transepithelial potential (V(t)) was 0.1 mV, and the short-circuit current was less than 1 microA cm(-2). Removal of Na(+) from mucosal saline decreased Cl(-) absorption by 56% and removal of Cl(-) decreased Na(+) absorption by 69%. However, active net absorption of both Na(+) and Cl(-) was not abolished when Cl(-) or Na(+) was replaced with an impermeant ion (gluconate or choline, respectively). Under physiological conditions with artificial urine (¿Na(+) = 2.12 mM, ¿Cl(-) = 3.51 mM) bathing the mucosal surface and saline bathing the serosal surface, transepithelial potential (V(t)) increased to a serosal positive approximately +7.6 mV. Unidirectional influx rates of both Na(+) and Cl(-) were 10-20-fold lower but active absorption of both ions still occurred according to the Ussing flux ratio criterion. Replacement of Na(+) with choline, or Cl(-) with gluconate, in the mucosal artificial urine yielded no change in unidirectional influx of Cl(-) or Na(+), respectively. However, kinetic analyses indicated a decrease in maximum Na(+) transport rate (J(max)) of 66% with no change in affinity (K(m)) in the low Cl(-) mucosal solution relative to the control solution. Similarly, there was a 79% decrease in J(max) values for Cl(-), again with no change in K(m), in the low-Na(+) mucosal bathing. The mucosal addition of DIDS, amiloride or bumetanide (10(-4) M) had no effect on either Na(+) or Cl(-) transport, under either symmetrical saline or artificial urine/saline conditions. Addition of the three drugs simultaneously (10(-4) M), or chlorothiazide (10(-3) M), under symmetrical saline conditions also had no effect on Na(+) or Cl(-) transport rates. Cyanide (10(-3) M) addition to mucosal artificial urine caused a slowly developing decrease of Na(+) influx to 59% and Cl(-) influx to 50% in the period after drug addition. Na(+) and Cl(-) reabsorption appears to be a partially coupled process in the urinary bladder of O. mykiss; transport mechanisms are both dependent upon and independent of the other ion.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗