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Blocking action of terodiline on calcium channels in single smooth muscle cells of the guinea pig urinary bladder.

The blocking action of terodiline, a nonspecific organic Ca++ antagonist, on smooth muscle Ca++ channels of the guinea pig urinary bladder was investigated. Inward Ca++ currents were recorded from smooth muscle cells isolated from the urinary bladder using the whole-cell patch-clamp technique. In the absence of terodiline, a use-dependent reduction in the amplitude of inward Ca++ current was observed at a stimulus frequency of 0.2 Hz. When terodiline (1-10 microM) was applied, the use-dependent reduction was accelerated markedly, depending on the stimulus frequency. The blocking action of terodiline was also dose-dependent; the Kd value as measured at the end of 20 times repetitive stimulation at 0.2 Hz was 1.7 microM. In addition to such a use-dependent block, terodiline produced a hyperpolarizing shift in the steady-state inactivation curve. The results suggest that terodiline preferentially binds to the Ca++ channel in the open state and also in the inactivated state.

Action Potentials↗

Lithotripsy of urinary bladder stones with a mechanical lithotriptor inserted through a narrow introducer. An experimental study in pigs.

Mechanical lithotripsy of urinary bladder stones was performed with the RotoLith lithotriptor in 8 pigs with implanted human stones or artificial stones after open cystotomy. The effect of the treatment on the urinary bladder was investigated macro- and microscopically immediately after the lithotripsy in 4 animals and 4 weeks after the lithotripsy in the other 4 animals. The stones were fragmented into very small pieces which would have been possible to pass with the urine. The histopathologic examination immediately after the procedure showed slight mucosal edema, patches of erosions in the mucosa, and minor submucosal bleeding. Microscopic examination of the bladders removed 4 weeks after lithotripsy showed slight chronic inflammation. The experimental results have encouraged us to plan to use this lithotripsy procedure in selected patients with bladder stones.

Animals↗

Rupture of uterine scar with extrusion of twin fetuses into the urinary bladder--a case report.

An unusual presentation of a ruptured uterus with extrusion of twin fetuses into the urinary bladder is described. A routine pelvic ultrasound to confirm pelvic collection from a suspended criminally induced abortion revealed a rupture of the anterior wall of the uterus with communication to the urinary bladder and this finding was confirmed at laparatomy. While a high index of suspicion is important in the diagnosis of ruptured uterus, a subtle place for pelvic ultrasound in patients with vaginal bleeding, suprapubic pain and haematuria may be of help.

Adult↗

Urinary bladder carcinogenicity of dimethylarsinic acid in male F344 rats.

The present study was conducted to determine the carcinogenicity of dimethylarsinic acid (DMA) administered to male F344 rats in a 2 year bioassay. A total of 144 rats (10 weeks old at the start) were divided into four groups of 36 rats each. Groups 1-4 received DMA (purity 100%) at concentrations of 200, 50, 12.5 and 0 p.p.m. in the drinking water, respectively, for 104 weeks. From weeks 97 to 104, urinary bladder tumors were observed in 12 of 31, eight of 31 and none of 33 in groups 1-3, respectively. No bladder tumors were observed in group 4. The present study demonstrated that long-term p. o. administration of DMA induced urinary bladder carcinomas in male F344 rats. Therefore, the results indicate that DMA is carcinogenic for the rat urinary bladder, which may be related to the human carcinogenicity of arsenicals.

Administration, Oral↗

[The detection of high risk human papillomaviruses in papillary transitional cell carcinoma of urinary bladder].

OBJECTIVE: To investigate the histological evidence of high risk human papillomavirus infection in bladder cancer. METHODS: 52 cases of papillary transitional cell carcinoma of the urinary bladder were studied for the incorporation of high risk human papillomavirus type 16 and type 18 DNA by non-isotopic in situ hybridization (NISH). RESULTS: 19 of 52 cases (36.5%) were positive for HPV DNA with punctuate and/or diffuse purple-blue staining in the nucleus of cancer cells, including two cases positive both for HPV16/18. HPV DNA were predominantly expressed in superficial tumors. Among these positive tumors, adjacent normal epithelium and Brunn's nests also showed positive staining. Morphologically, HPV positive cells existed in the whole layer of papillary tumor cells, 3 of them presented koilocytoid change. CONCLUSIONS: HPV infection might be a common event in urinary bladder and a potential factor for carcinogenesis of bladder cells.

Adult↗

Chondrosarcoma of the urinary bladder and establishment of a human chondrosarcoma cell line (OCUU-6).

Chondrosarcoma is a very rare tumor of the urinary bladder, with only 4 cases reported to date. In this study, we report on a case of a 73-year-old male who presented bladder mass and right hydroureteronephrosis. Radical cystectomy, right nephrectomy and left ureterocutaneoustomy were performed, and histological study disclosed chondrosarcoma of the urinary bladder. As reported in other cases, the tumor was highly aggressive with a short clinical course, and the patient died of carcinomatous pleuritis at one month after surgery. Subsequently, we successfully established a human chondrosarcoma cell line (OCUU-6) from the pleural effusion of the patient.

Aged↗

Chondrosarcoma of the urinary bladder and establishment of a human chondrosarcoma cell line (OCUU-6).

Chondrosarcoma is a very rare tumor of the urinary bladder, with only 4 cases reported to date. In this study, we report on a case of a 73-year-old male who presented bladder mass and right hydroureteronephrosis. Radical cystectomy, right nephrectomy and left ureterocutaneoustomy were performed, and histological study disclosed chondrosarcoma of the urinary bladder. As reported in other cases, the tumor was highly aggressive with a short clinical course, and the patient died of carcinomatous pleuritis at one month after surgery. Subsequently, we successfully established a human chondrosarcoma cell line (OCUU-6) from the pleural effusion of the patient.

Aged↗

Pathogenesis of acute radiation effects in the urinary bladder. Experimental results.

PURPOSE: The present review summarizes experimental studies of the pathogenesis of acute radiation-induced changes in urinary bladder function. MATERIAL AND METHODS: Transurethral cystometry was used for longitudinal assessment of bladder function in mice. With this technique, radiation-induced changes in storage capacity can be quantified. In histological studies, changes in urothelial cell density and in urothelial protein expression during the acute radiation response were determined. Acetylsalicylic acid (ASA) was used for the treatment of acute functional changes. RESULTS: The histological studies did not reveal any systematic fluctuations in urothelial cell density during the time of the acute radiation response. However, characteristic changes in the expression of proteins associated with urothelial cell function, differentiation and cell contact were observed, which correlated with the functional impairment. By local or systematical application of ASA, a significant restoration of bladder function compared to placebo treatment could be achieved. CONCLUSION: Acute functional radiation effects in the urinary bladder are not based on urothelial denudation. However, changes in protein expression indicate an impairment of the urothelial barrier function. The results of ASA treatment demonstrate that prostaglandins are involved in the response. Alterations in urothelial or endothelial prostaglandin metabolism may be primarily radiation-induced or secondary because of the impaired urothelial barrier.

Animals↗

Molecular genetic evidence for a common clonal origin of urinary bladder small cell carcinoma and coexisting urothelial carcinoma.

In most cases, small-cell carcinoma of the urinary bladder is admixed with other histological types of bladder carcinoma. To understand the pathogenetic relationship between the two tumor types, we analyzed histologically distinct tumor cell populations from the same patient for loss of heterozygosity (LOH) and X chromosome inactivation (in female patients). We examined five polymorphic microsatellite markers located on chromosome 3p25-26 (D3S3050), chromosome 9p21 (IFNA and D9S171), chromosome 9q32-33 (D9S177), and chromosome 17p13 (TP53) in 20 patients with small-cell carcinoma of the urinary bladder and concurrent urothelial carcinoma. DNA samples were prepared from formalin-fixed, paraffin-embedded tissue sections using laser-assisted microdissection. A nearly identical pattern of allelic loss was observed in the two tumor types in all cases, with an overall frequency of allelic loss of 90% (18 of 20 cases). Three patients showed different allelic loss patterns in the two tumor types at a single locus; however, the LOH patterns at the remaining loci were identical. Similarly, the same pattern of nonrandom X chromosome inactivation was present in both carcinoma components in the four cases analyzed. Concordant genetic alterations and X chromosome inactivation between small-cell carcinoma and coexisting urothelial carcinoma suggest that both tumor components originate from the same cells in the urothelium.

Aged↗

[Cavernous hemangioma of urinary bladder associated with angiokeratoma of the left leg].

A 45-year-old male was admitted to our hospital with a complaint of asymptomatic macroscopic hematuria. At cystoscopy a multi-lobulated, dark red tumor, the size of a rice grain, was found on the right lateral wall. He also had a 5 X 4 mm purplish skin tumor on the left leg. Double contrast cystogram also showed the shape of the tumor on the right lateral wall of bladder. Based on the aforementioned findings, we diagnosed this case as hemangioma of the urinary bladder associated with the same lesion on the left leg. The bladder tumor was resected transurethrally and the skin lesion was also excised. Pathological diagnoses were cavernous hemangioma of bladder and angiokeratoma of skin, respectively. Including our case we found 62 cases of hemangioma of the urinary bladder in the Japanese literature. Only 5 of them were associated with the hemangiomas of other regions of the body.

Angiokeratoma↗

Ureterocolonic anastomosis in a dog with transitional cell carcinoma of the urinary bladder.

Ureterocolonic anastomosis and cystectomy were performed in a dog for treatment of transitional cell carcinoma of the urinary bladder. The dog remained an acceptable house pet for 10 months after surgery. However, the tumor recurred 10 months after surgery, and the dog was euthanatized. Our results indicated that the combination of ureterocolonic anastomosis and cystectomy can be an acceptable form of palliative treatment for transitional cell carcinoma of the urinary bladder in the dog.

Animals↗

Inverted papilloma of the urinary bladder in children: case report and review of prognostic significance and biological potential behavior.

Inverted papilloma of the urinary bladder is rare in the pediatric population. Despite several reports in the literature the prognostic significance and biological potential behavior of this lesion remain uncertain. The authors report a case of polypoid inverted papilloma of the urinary bladder in an 11-year-old boy and review its pathology. The pediatric population with this lesion is an ideal group to provide intense, long-term follow-up to define the biological behavior and prognosis significance of this lesion.

Child↗

Effect of distension on adrenergic innervation of the rat urinary bladder.

The effect of distension on adrenergic innervation was investigated in the rat urinary bladder. Bladders were distended for 3 h by forced diuresis and balloon obstruction, and specimens were taken from the bladder dome, body and neck for the demonstration of glyoxylic acid-induced fluorescence of catecholamines. Depletion of catecholamines started after 10 h and was almost complete after 2 days. The fluorescence had recovered part way after 5-7 days and was practically normal after 21 days. Small, intensely fluorescent (SIF) cells in the ganglia continued to leak catecholamines throughout the 21-day study period. The primary clinical success of distension therapy for the treatment of unstable bladder may be at least partly due to a reversible disturbance in the function of the adrenergic nerves, which have an excitatory alpha-adrenergic dominance in such cases, but the persistent leakage from SIF cells raises the question of whether distension causes prolonged disturbances in bladder function.

Animals↗

Direct DNA sequencing of the rat neu oncogene transmembrane domain reveals no mutation in urinary bladder carcinomas induced by N-butyl-N-(4-hydroxybutyl)nitrosamine, N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide or N-methyl-N-nitrosourea.

Epidermal growth factor (EGF) and EGF-related growth factors are present in the urine, and EGF has been identified as a urinary component that enhances urinary bladder tumor formation in rats. Neu oncogene encodes a cell surface receptor similar to the EGF receptor and is known to be activated by a point mutation of DNA that encodes the transmembrane domain of the neu protein (p185). In this study, we examined the possible mutational activation of neu oncogene in 50 urinary bladder transitional cell carcinomas (TCC) induced in F344 rats by the following carcinogenesis models: (i) 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) (4 weeks)----3% uracil (20 weeks); (ii) 0.2% N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) (6 weeks)----5% sodium saccharin (72 weeks); and (iii) N-methyl-N-nitrosourea (MNU) 20 mg/kg body wt, i.p. twice per week for 4 weeks----3% uracil (20 weeks). The DNA sequence around the transmembrane domain of neu gene was amplified by PCR and sequenced. The results showed no mutation within the examined DNA sequences, indicating that neu oncogene is not activated by a point mutation in the transmembrane domain in urinary bladder carcinomas induced by BBN, FANFT or MNU.

Amino Acid Sequence↗

Effect of stimulation of anterior hypothalamic area on urinary bladder function of the anesthetized rat.

The hypothalamus is a key area for the integration of the autonomic features of affective behavior. Hypothalamic defence area (HDA) stimulation evokes major cardiorespiratory changes as well as modifications of general autonomic activity both in the anesthetized and conscious animal. Micturition is due to an increase in pelvic parasympathetic activity and, in the cat, the anterior hypothalamus has been implicated in urinary bladder control with the demonstration of a dorsolateral vesicoconstrictor pathway and a ventromedial inhibitory pathway. In this study we have investigated the effect of electrical and chemical stimulation of the HDA on bladder pressure and contractions in rat. Female rats (n = 15) were anesthetized, paralyzed and ventilated artificially. Arterial blood pressure, heart rate, urinary bladder pressure and pelvic nerve activity were recorded. HDA was electrically (1 ms, 100 Hz, 5-10 s train at intensities up to 150 micro A) and chemically (sodium glutamate, 50 nl, 2mM) stimulated. For statistical analysis the t-test was used, data were expressed as mean +/- SEM. Values of t were taken as significant when p < 0.05.HDA stimulation at 100-150 micro A evoked changes of both mean blood pressure (mBP) and bladder pressure (BlP). However, stimulation at < 30 micro A allowed a distinction within HDA of two different regions, at the same antero-posterior and lateral level, but separated 100-150 micro m in depth, which evoked differential effects on blood pressure and urinary bladder pressure. Results show that low intensity stimulation at ventral sites evoked a significant increase of mBP (from 102 +/- 5.9 to 127 +/- 8.6 mmHg, n = 10, p < 0.0001) with little changes of BlP (from 12 +/- 2.2 to 16 +/- 2.9 cmH(2)O, n = 10, p < 0.0005), whilst at more dorsal sites significant increases of BlP were elicited (from 12 +/- 8.3 to 38 +/- 4.6 cmH(2)O,n = 10, p < 0.0001) with only a small rise of mBP (from 102 +/- 6.2 to 111 +/- 9.8 mmHg, n = 10, p < 0.005). Glutamate injections at dorsal sites evoked a rise of BlP (from 11 +/- 2.2 to 30 +/- 3.0 cmH(2)O (n = 5; p < 0.0001) with small changes in BP, whilst at ventral sites (n = 4) glutamate microinjections evoked changes in BP but not of BlP. In conclusion stimulation at different sites within HDA can elicit separate changes in BP and BlP.

Anesthesia↗

Extra-adrenal pheochromocytoma (paraganglioma) of the urinary bladder: a case report.

The case of a 49-year-old male patient with paraganglioma of the urinary bladder is presented here. The patient's only complaint was of gross hematuria: sustained hypertension and post-micturitional hypertension were not presented. Transurethral resection was performed to diagnose the bladder tumor. Pathological examination resulted in the diagnosis that the resected tissue was a paraganglioma. Computed tomography, magnetic resonance imaging and iodine-131-labeled metaiodbenzylguanidine scintigraphy revealed that the tumor was a primary paraganglioma in the urinary bladder. Plasma concentrations of the catecholamines were virtually within the normal limits. Hypertensive crisis was not revealed during the transurethral resection. The tumor was non-functional. Partial cystectomy was performed. The patient has remained disease-free for five months after surgery.

Biomarkers, Tumor↗

Inhibitory action of alpha-difluoromethylornithine on N-butyl-N-(4-hydroxybutyl)nitrosamine-induced rat urinary bladder carcinogenesis.

We previously have shown that urine components capable of stimulating ornithine decarboxylase activity of urothelium can enhance rat urinary bladder carcinogenesis, and that alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, suppresses carcinogen-initiated rat urinary bladder carcinogenesis. The present investigation was conducted to determine whether DFMO's suppressive effect is stage specific during carcinogenesis and whether the suppressive effect lasts with its continued use. Following initiation with 0.05% N-butyl-N-(4-hydroxybutyl)-nitrosamine in drinking water for 6 wk, male Fischer 344 rats initially weighing 125 to 150 g were randomly divided into two groups, the first receiving 0.2% DFMO in drinking water ad libitum and the second receiving tap water only. Groups of animals were killed at regular intervals until the completion of the experiment at 75 wk. The effect of DFMO was evaluated by monitoring the incidence of tumors, the mean number of tumors per rat, the mean volume of individual tumors, and the mean total tumor volume per rat. The results showed that continuous treatment with DFMO significantly reduced tumor formation until 60 wk (P less than 0.017). The effect was only of borderline significance (0.017 less than P less than 0.035) at 75 wk. Discontinuation of DFMO treatment at 40 wk resulted in the loss of protective effect in all comparisons except for the borderline effect on the tumor number and total tumor volume per rat. DFMO had no significant effect on the incidence or development of preneoplastic early lesions. Mucosal polyamine (spermidine and spermine) levels were reduced and correlated well with the reduction in tumor growth, suggesting that the reduction in tumor growth rate by DFMO may be due to its ability to reduce polyamine levels in urothelium. There were no side effects attributable to DFMO treatment. DFMO may be a useful chemopreventive agent to retard the recurrence of human superficial bladder cancer.

Animals↗

Evidence of nonadrenergic, noncholinergic contraction in rat urinary bladder by 1,1-dimethylphenylpiperazinium stimulation in vivo.

Nonadrenergic, noncholinergic (NANC) contraction has been demonstrated in animal urinary bladder. However, the exact nature of the NANC innervation is still unclear. 1,1-Dimethylphenylpiperazinium (DMPP), which generates action potentials in the cell body of the postganglionic neuron and causes neurotransmitter release (both acetylcholine and noradrenaline), was given intravenously (0.1-0.7 mg/kg) to 3-month-old female Wistar rats under anesthesia (n = 20). Intravesical pressure, heart rate and blood pressure of the rats were monitored on Gould polygraph. Monophasic dose-dependent contractile response was observed upon administration of DMPP in 12 of 20 rats. After total adrenergic and cholinergic blockade with atropine, guanethidine, phentolamine and propranolol, the contractile response was reduced, not completely, in the animals. At the dose of 0.7 mg/kg, the contraction was reduced to about 48% of the original response. The study provides in vivo evidence for NANC contraction in the rat urinary bladder, moreover, the neurotransmitter is released from the postganglionic neurons.

Action Potentials↗