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Reserpine-induced detrusor hyperreflexia: an in vivo model for studying smooth muscle relaxants at urinary bladder level.

A new in vivo model for studying the effects of smooth muscle relaxant drugs at urinary bladder level has been developed. This involves the determination of a cystometrogram at a physiological filling rate in urethane anesthetized rats. The amount of infused saline required to elicit TTX-sensitive rhythmic contractions (micturition reflex) of urinary bladder was choosen as end point to evaluate the effect of test substances. Reserpine pretreatment significantly reduced the volume of saline required to elicit the micturition reflex. The effect of reserpine can be reproduced by intravenous prazosin, but not by propranolol or yohimbine, in control rats. Intravenous, but not topical, hexamethonium reversed the effects of reserpine pretreatment on the amount of infused saline required to elicit rhythmic contractions. The nature of rhythmic contractions produced by saline filling of the urinary bladder in these experimental conditions, as well as the potential mechanism(s) involved in the effects of reserpine, are discussed in view of the existing literature on the physiology and pharmacology of the micturition reflex. The effects of various drugs commonly used to produce a relaxation of bladder muscle suggest that this model might be useful for detecting substances of potential therapeutic usefulness in the treatment of bladder hypermotility disorders.

Animals↗

Paraganglioma of the urinary bladder: can biologic potential be predicted?

BACKGROUND: Paraganglioma of the urinary bladder is rarely encountered and its biologic behavior is uncertain. The authors sought to determine the prognostic factors that would predict patient outcome. METHODS: The Mayo Clinic experience over 53 years with paraganglioma of the bladder was reviewed. All histologic slides from 16 patients were reviewed by the authors. Eight cases were examined immunohistochemically with cytokeratin (AE1/3, cytokeratin 7, and cytokeratin 20), vimentin, S-100 protein, neuroendocrine markers (chromogranin, synaptophysin, and neuron specific enolase), p53 protein, and MIB-1. DNA ploidy was determined by digital image analysis in formalin fixed, paraffin embedded tissue. The mean follow-up was 6.3 years (range, 0.4-16.4 years). RESULTS: Paraganglioma usually occurred in young adult women (mean age, 45 years; range, 16-74 years). The male-to-female ratio was 1 to 3. The common symptoms and signs were hypertension and hematuria. The tumors were usually located intramurally in the lateral and posterior wall of the bladder and were multifocal in 3 cases (18%). Seven patients were treated by transurethral resection, eight by partial cystectomy, and one by radical cystectomy. T classification was T1 (1 patient), T2 (9 patients), T3 (2 patients), and T4b (4 patients). At the time of diagnosis, one patient had distant metastasis and one had regional lymph node metastasis. One patient developed metastasis 1 year after diagnosis and died of the disease 1.5 years later. None of the patients with T1 or T2 tumors had recurrence or tumor progression. All tumors were aneuploid. The mean MIB-1 labeling index was 1.5% (range, 0.03-7.0%). The tumor cells displayed immunoreactivity for S-100 protein and neuroendocrine markers and were negative for p53 (except 1 case) and cytokeratin. CONCLUSIONS: Paraganglioma of the urinary bladder occurs mostly in young adult women. Patients with tumor of advanced classification (>/=T3) are at risk of recurrence, metastasis, and dying of the disease, whereas patients in this study with T1 or T2 disease had favorable outcomes after complete tumor resection.

Adolescent↗

Pharmacological evidence for the existence of two components in the twitch response to field stimulation of detrusor strips from the rat urinary bladder.

Isolated strips from the anterior dome of the rat urinary bladder respond to single pulse field stimulation with a contraction. Two distinct components of this contraction ("early' and "late') could be observed, both of which were unaffected by hexamethonium (10 microM) and almost abolished by tetrodotoxin (1 microM) indicating their dependence on neurotransmitter release from postganglionic nerve endings. Atropine (3 microM) inhibited the "late' component (over 60%) to a significantly greater extent than the "early' component (less than 10%) Amplitude of the "early' component was usually greater than that of the "late' component. There was almost no difference between the "early' and "late' component in respect of their relationship to stimulus strength and pulse duration. Physostigmine (0.03 microM) enhanced both components of the nerve-mediated contraction, although enhancement of the "late' component was much greater than that of the "early' one. Tetraethylammonium (TEA, 0.5-5 mM) enhanced, in a concentration-related manner, both "early' and "late' components of the nerve-mediated contraction. Following exposure to physostigmine or TEA (5 mM) both "early' and "late' components of contraction were almost completely inhibited by tetrodotoxin. Atropine inhibition was more evident on the "late' as compared to "early' component of contraction. These findings demonstrate the presence, in the twitch response of rat isolated urinary bladder to field stimulation, of two nerve-mediated components which exhibit a different susceptibility to atropine and physostigmine.

Animals↗

Increased expression of cyclooxygenase-2 protein in rat urinary bladder tumors induced by N-butyl-N-(4-hydroxybutyl) nitrosamine.

The anti-inflammatory drugs, aspirin and piroxicam, are known to possess chemopreventive potential against rat superficial urinary bladder carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Recently, we found similar inhibitory effects with a selective cyclooxygenase (COX)-2 inhibitor, nimesulide. In order to clarify the inhibitory mechanisms, we have further studied the expression of COX-2 protein in urinary bladder tumors induced by BBN in Fischer 344 male rats. For comparison, papillomatosis caused by uracil-induced urolithiasis, and normal epithelial cells, were also investigated. Western blot analysis revealed COX-2 protein to be barely expressed in the normal epithelial cells, whereas it was increased 13-22-fold in varying sizes of urinary bladder tumors and 7-fold in papillomatosis. Immunohistochemically, COX-2 protein was diffusely expressed in transitional cell carcinomas and nodulo-papillary hyperplasia but weakly expressed only in basal cells in simple hyperplasia and normal-looking surrounding epithelia. In papillomatosis, it was moderately expressed only in endothelial cells in stroma. These results indicate that COX-2 plays important roles in the development of preneoplastic and neoplastic lesions in the rat urinary bladder, and therefore could be a good target for chemoprevention of superficial lesions.

Animals↗

Primary choriocarcinoma of the urinary bladder in association with undifferentiated carcinoma.

A carcinoma of the urinary bladder with a distinct choriocarcinomatous component that developed in a postmenopausal woman was associated with high titers of circulating chorionic gonadotropin. The diagnosis was supported by histochemical demonstration of human chorionic gonadotropin in syncytial tumor giant cells and electron microscopic features consistent with syncytiotrophoblastic cell differentiation.

Carcinoma↗

Effect of partial outlet obstruction on 14C-adenine incorporation in the rabbit urinary bladder.

Bladder outlet obstruction induces severe changes in urinary bladder function and metabolism. These changes are characterized by significant reductions in the ability of the in vitro whole bladder to generate pressure and to empty. Metabolically, partial outlet obstruction induces a shift from oxidative to anaerobic metabolism. The decreased oxidative metabolism is mediated in part by significant decreases in mitochondrial substrate metabolism, which in turn is correlated with decreased activity of 2 important mitochondrial enzymes: citrate synthase and malate dehydrogenase. The present study was designed to evaluate mitochondrial function by studying the incorporation of 14C-adenine into high-energy phosphates (ATP, AMP, and ADP). Mild partial outlet obstructions were created by surgically placing silk ligatures loosely around the bladder neck. The results of these studies demonstrate that after 60 min incubation in oxygenated medium containing glucose + 1uCi14C-adenine, 1) There was no significant differences in the total AMP, ADP, and ATP concentrations measured in bladders taken from controls, 7- and 14-day obstructed rabbits; 2) there was no effect of obstruction on either the concentration of 14C-AMP in the tissue or in the ratio of hot to cold AMP; and 3) there was a 50% decrease in the concentration of 14C-ADP and a 70% decrease in the concentration of 14C-ATP in the bladder smooth muscle obtained from obstructed tissue (from both 7- and 14-day obstructions) compared to concentration in the control bladder smooth muscle. These results confirm the previous finding that obstruction did not reduce the rate of incorporation of adenine to AMP within the obstructed bladder smooth muscle and extends these studies to identify a significant reduction in the synthesis of both ADP and ATP. These results support the hypothesis that partial outlet obstruction induce a major dysfunction in mitochondrial function, both in the ability to oxidize substrates and in the ability to generate ATP.

Adenine↗

Non-papillary carcinoma in situ of the urinary bladder. An electron microscopic study.

A case of non-papillary carcinoma in situ of the urinary bladder was presented with ultrastructural descriptions. Dysplastic urothelial cells had a large nucleus with prominent nucleoli and increased euchromatin. The nuclei had a wavy outline with irregular invaginations. Cytoplasmic organella were immature and fairly good amount of glycogen particles existed in the cytoplasm. Among the dysplastic cells, there are two types of epithelium, one which has irregular pleomorphic cytoplasmic processes and the other which has relatively smooth cell borders. Both types had few poorly developed desmosome-like cell attachments and wide intercellular space. This study revealed that decreased numbers of desmosome-like attachments and wide intercellular space with or without cytoplasmic processes of non-papillary transitional cell carcinoma of the urinary bladder might be a morphologic expression of loss of cohesiveness in this type of carcinoma.

Aged↗

Absence of ras oncogene activation in rat urinary bladder carcinomas induced by N-methyl-N-nitrosourea or N-butyl-N-(4-hydroxybutyl)nitrosamine.

Previously, we demonstrated point mutations of the H-ras gene in N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT)-induced rat urinary bladder carcinomas. In this study, ras oncogene activation was examined in urinary bladder carcinomas induced by N-(4-hydroxybutyl)nitrosamine (BBN) or N-methyl-N-nitrosourea (MNU) administration followed by uracil treatment. In the first experiment, MNU (20 mg/kg body wt) was i.p. injected into 11 male F344 rats twice a week for 4 weeks, followed by feeding 3% uracil for 20 weeks (MNU/uracil group). Ten rats were given only 3% uracil without MNU pretreatment. In the second experiment, 20 male F344 rats were given 0.05% BBN in the drinking water for 4 weeks, then fed 3% uracil for 20 weeks (BBN/uracil group). Another 20 rats were fed 3% uracil without the BBN pretreatment. Transitional cell carcinomas were induced in the urinary bladder of all rats in the MNU/uracil and BBN/uracil groups. Papillomas and hyperplasias were present in the rats given uracil without prior BBN or MNU. DNA and protein were extracted from the tumors (MNU/uracil or BBN/uracil groups) or from the scraped bladder epithelium (uracil alone groups). Sequences around codons 12, 13 and 61 of H-, K- and N-ras genes were examined by direct sequencing after polymerase chain reaction, and p21 was examined by Western blotting. No mutation was found within the examined sequences and p21 showed no changes in mobility. There was no difference in the level of p21 expression between rats treated with MNU/uracil or BBN/uracil compared to corresponding uracil alone groups. These results indicate that the ras oncogene was not activated in urinary bladder carcinomas induced by BBN or MNU in combination with uracil treatment, in contrast to previous findings with FANFT.

Animals↗

Emergence of an epidermis-associated cell surface antigen in epithelial cells of the rat urinary bladder in carcinogenesis.

Inbred ACI/rats were treated with a selective urinary bladder carcinogen N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). Two cell surface antigens on the epithelial cells of the bladder, normal bladder epithelium (NBE) antigen unique to normal epithelial cells of the bladder and BC-SK antigen specific for bladder cancer and epidermis, were periodically assayed by mixed hemadsorption test with the typing sera against each antigen. Treatment with BBN for 8 or more weeks induced papillomas or cancers that expressed a definite level of BC-SK antigen, whereas a 4-week treatment did not render the bladder cells with a significant level of this antigen. In general, the level of NBE antigen in bladder cells was not altered by the BBN treatment. In vitro culture of bladder cells of BBN-treated rats resulted in an increase in the level of BC-SK antigen as opposed to a decrease in the NBE antigen level. BC-SK antigen was not detected in epidermal cells of rats younger than 3 days, but it emerged in these cells by in vitro culture for longer than 4 days.

Animals↗

[Uretero-enteral anastomosis of dilated ureters in ileocecal replacement of the urinary bladder].

In very dilated efferent urinary pathways with an impaired peristaltic activity of the ureter the authors selected for ureteroenteral anastomosis in ileocoecal replacement of the urinary bladder anastomosis with the ileum, leading into the ileocoecal reservoir via the invaginated trans-Bauhin's ileal valve. This valve was ensured against devagination by a transparietal suture after longitudinal intraluminal discision of the outer leaf the invaginate. By adjusting the discision of the outer leaf of the invaginate the authors obtained the selected pressure resistance of the valve which was desirable from the clinical aspect. This technique was described in two patients who were followed up for 6 and months and in a patient with convercion of Bricker's conduit into an ileocoecal prosthesis.

Anastomosis, Surgical↗

Metabolic fate of N, N-dipropylnitrosamine and N, N-diamylnitrosamine in the rat, in relation to their lack of carcinogenic effect on the urinary bladder.

The metabolic fate of N, N-dipropylnitrosamine (DPN) and N, N-dipentyl-(=diamyl) nitrosamine (DAN), which induced tumors principally in the liver and esophagus but not in the urinary bladder, was studied in the rat, in order to elucidate the reason for this lack of carcinogenicity to the urinary bladder in contrast with the butyl homolog, N, N-dibutylnitrosamine (DBN), a potent bladder carcinogen. The principal urinary metabolite of DPN was identified as the omega-oxidation product N-propyl-N-(2-carboxyethyl) nitrosamine. The (omega-1)-oxidation product N-propyl-N-(2-hydroxypropyl) nitrosamine and its glucuronic acid conjugate were also characterized as metabolites. The principal urinary metabolite of DAN was N-amyl-N-(2-carboxyethyl) nitrosamine, which was formed by metabolic shortening of the amyl chain by omega- and beta-oxidations according to the Knoop mechanism. Besides this, seven compounds oxidized at omega-, (omega-1)-, (omega-2)-, and (omega-3)- positions of one or both amyl chains were isolated and characterized, some of which were shown to be also present as the corresponding glucuronide. The metabolic pattern of DPN and DAN was compared with that of DBN, and the lack of carcinogenicity of the former N-nitrosamines to the urinary bladder of rats is discussed on the basis of their urinary metabolites.

Animals↗

Insulin cells are found in the main and accessory urinary bladders of the painted turtle, Chrysemys picta.

Insulin has been localized immunocytochemically to cells in the main and accessory urinary bladders of the painted turtle, Chrysemys picta, and represents an unusual addition to the specturm of regulatory peptides associated with the urinary bladder. These stellate to fibroblastoid cells often possess neural-like processes and are similar in morphology to neurotensin cells found in Chrysemys and Pseudemys urinary bladders. Radioimmunoassay of 2M acetic acid extracts of bladder tissue indicate that the insulin concentration of accessory bladder is several-fold greater than main bladder but considerably lower than the insulin content of pancreas. Pieces of accessory bladder incubated in vitro exhibit a stable insulin release into the medium over 1 hour, but release is unaltered by known insulin secretagogues. It is tempting to postulate an endocrine or paracrine regulatory function for these cells, but at present their role in Chrysemys bladder function remains unknown.

Animals↗

Perforation of the augmented urinary bladder in nine children and adolescents: importance of cystography.

Augmentation of the urinary bladder is a popular surgical procedure for increasing the capacity and lowering the intraluminal pressure in patients whose bladder is small, noncompliant, or has high pressure. Among 250 augmentations performed at our hospital, nine patients have had 16 episodes of postoperative extravasation of urine from their augmented bladder. Thirteen episodes were studied by fluoroscopically monitored contrast cystography, which was diagnostic in 12. One patient's perforation was noted during an unrelated operation and the other two died of peritonitis before cystography could be performed. Four episodes occurred early, within 3 weeks of surgery. All were at a surgical anastomosis and presumably represented incomplete healing. Each patient with an early episode of extravasation had a perforation later. Nine perforations occurred from 1.0 to 6.5 months after the augmentation. Of these, three occurred at an anastomosis and four occurred in the augmenting segment. The locations of two were never fully documented. Three perforations occurred late, from 2.5 to 6.0 years after surgery, and all were in the augmenting segment. Three of the nine patients died of complications associated with perforation. Perforation of the bladder is not rare and is a potentially fatal complication of augmentation. Whenever a patient who has undergone augmentation has signs or symptoms suggesting perforation, cystography can play a crucial role in diagnosis and should be performed without delay.

Adolescent↗

Smooth muscle neoplasia of the urinary bladder wall in three dogs.

Smooth muscle origin neoplasia of the urinary bladder wall is rare in dogs. This report describes the ultrasonographic features of two bladder wall leiomyomas and one bladder wall leiomyosarcoma. All three dogs had a single, smoothly marginated, round, hypo to mixed echogenicity intraluminal mass in the urinary bladder. Based on color Doppler examination of the masses, there was no visible blood flow.

Animals↗

Prognostic-factors-based risk-stratification model for invasive urothelial carcinoma of the urinary bladder in Taiwan.

Objectives. To develop a prognostic-factors-based predictive model for invasive urothelial carcinoma of the urinary bladder derived from statistical comparison of clinical characteristics.Methods. The medical records for patients with invasive urinary bladder urothelial carcinoma were reviewed. Clinical data for age, sex, serum lactate dehydrogenase, creatinine, albumin, alkaline phosphatase, alanine aminotransferase, total bilirubin and hemoglobin levels, white blood cell and platelet counts, positive urine cytology, Eastern Cooperative Oncology Group performance status score, tumor size, histologic grading, T stage, presence of lymph node metastases, squamous differentiation, hydronephrosis, prostatic involvement, Charlson comorbidity index, surgical procedures, and adjuvant chemotherapy status were recorded. Univariate and multivariate analyses were performed to test independent factors for prediction of survival and disease recurrence.Results. After univariate and multivariate analyses, six independent prognostic factors were found: T stage, grading, prostatic involvement, Eastern Cooperative Oncology Group performance status score, and pretreatment serum creatinine and albumin levels. A scoring system was developed on the basis the relative risk associated with the proposed prognostic factors and patients were stratified into three groups according to their scores, with statistically significant prognostic differences revealed for each of the between-group comparisons. Independent factors affecting recurrence-free survival and best predicted disease recurrence were pretreatment serum creatinine, T stage, and surgical procedure.Conclusions. This prognostic-factors-based risk-stratification model for invasive urothelial carcinoma of the urinary bladder may help clinicians predict outcome and select the most appropriate therapeutic modalities. The incidence of recurrent disease is significantly higher for patients with poor renal function before treatment or advanced T stage and those undergoing transurethral tumor resection instead of radical cystectomy.

Aged↗

[Urinary bladder displacement (lateroflexio vesicae urinariae) in the sow].

In older gravid sows in the last stage of gestation or after pariturition lateroflexion of the urinary bladder into the space between the vagina and the pelvic wall occasionally occurs. The reposition of the displaced urinary bladder by exerting external pressure either on the vulva or the perineum is usually unsuccessful. Only after the bladder has been emptied by a catheter spontaneous reposition does occur. In two cases displacement of the urinary bladder occurred immediately after normal pariturition. In both cases relapses were observed after the removal of the implanted balloon catheter. Both sows had the urinary balloon catheter reinserted and it was left in place until the weaning of the piglets. There were no complications during the whole lactation period. Both sows reared their piglets and could then be slaughtered.

Animals↗

Stereological estimates of nuclear volume in normal mucosa and carcinoma in situ of the human urinary bladder.

The nuclear volume of the epithelial cells in the human urinary bladder mucosa has been estimated using point sampled intercepts in vertical sections (local vertical windows). The study included 27 specimens: ten from normal bladder mucosa, five from inflamed mucosa, seven from mucosa with flat grade II lesions and five from mucosa with flat grade III lesions. After standard fixation, embedding, sectioning and haematoxylin-eosin staining an unbiased estimate of the mean volume of nuclei sampled with a chance proportion to the volume = vV = pi/3 x (l0)3 was calculated using a frame for orientating the linear test probe in vertical sections. Here l0 is the length of the intercept through a test point hitting a nucleus measured in a random direction through the test point. The weighted mean nuclear volume of bladder mucosa with grade II and grade III lesions (537 microns 3 and 494 microns 3 respectively) was significantly larger than the weighted mean nuclear volume of normal (133 microns 3) and inflamed bladder mucosa (182 microns 3). This simple and fast estimation of nuclear volume seems to provide objective data useful in discriminating between neoplastic and non-neoplastic lesions of the bladder mucosa.

Carcinoma in Situ↗

Urinary bladder metastases from breast carcinoma: review of the literature starting from a clinical case.

Bladder metastases from solid tumors are rare. Breast carcinoma cells seldom spread to the urinary bladder. We report the case of a patient with invasive breast carcinoma who developed a breast recurrence followed by bone and urinary bladder metastases. Starting from this clinical case we review the available literature on this issue. Only few cases of urinary bladder metastases from primary breast cancer have been reported, although the case reports have increased in recent years. Patients with breast cancer presenting with urinary symptoms should be examined for possible bladder metastases.

Breast Neoplasms↗