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PubMed2004

In vitro and in vivo tissue selectivity profile of solifenacin succinate (YM905) for urinary bladder over salivary gland in rats.

Solifenacin succinate [YM905; (+)-(1S,3'R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate monosuccinate] is a new muscarinic receptor antagonist developed for the treatment of overactive bladder. The aim of the present study was to evaluate the in vitro and in vivo bladder selectivity profile of solifenacin over salivary gland in the same animal species, and to compare the results with those obtained for tolterodine, oxybutynin, darifenacin and atropine. Solifenacin and the other antimuscarinic drugs inhibited carbachol-induced increases in intracellular Ca(2+) levels in bladder smooth muscle cells and salivary gland cells isolated from rats in a concentration-dependent manner. The inhibitory effect of solifenacin for bladder smooth muscle cells (pK(i)=8.12) was 3.6-fold more potent than that for salivary gland cells (pK(i)=7.57). In contrast, the inhibitory effects of the other antimuscarinic drugs for bladder smooth muscle cells were 1.7- to 2.2-fold more potent than those for salivary gland cells. In anesthetized rats, solifenacin dose-dependently inhibited carbachol-induced intravesical pressure elevation and salivary secretion, and exhibited functional selectivity (3.7- to 6.5-fold) for urinary bladder over salivary gland. Tolterodine was also 2.2- to 2.4-fold more selective in inhibition of bladder response. In contrast, oxybutynin, darifenacin and atropine did not show functional selectivity for urinary bladder. These results indicate that solifenacin exerts greater selectivity for urinary bladder over salivary gland than tolterodine, oxybutynin, darifenacin and atropine, and may consequently provide symptomatic benefit in the treatment of overactive bladder with less dry mouth than currently used antimuscarinic drugs.

Animals↗
PubMed1985

Cigarette smoke extracts inhibit prostacyclin synthesis by the rat urinary bladder.

Since prostacyclin (PGI2) is known to have a cytoprotective effect on epithelia, and since cigarette smoking is associated with an increased risk of bladder cancer, we investigated the possibility that nicotine, cotinine (the principal metabolite of nicotine) and other components of cigarette smoke inhibit PGI2 secretion by the urinary bladder. Using the rat urinary bladder as a model, we found that cigarette smoke extracts, but not nicotine or cotinine, inhibit in vitro PGI2 synthesis. 2-Naphthylamine, a known bladder carcinogen, was also a potent inhibitor of PGI2 synthesis by the rat bladder. It is possible that cigarette smoke and 2-napthylamine exert their carcinogenic effect partly through the inhibition of PGI2 synthesis, resulting in diminished urothelial cytoprotection.

2-Naphthylamine↗
PubMed1978

Eosinophilic infiltrates in carcinoma of the urinary bladder unassociated with schistosomiasis.

Two hundred and twenty-four biopsies from 151 patients with urinary bladder neoplasms have been studied in order to investigate the incidence of and possible causes for the infiltration of eosinophils. Cases of schistosomiasis were excluded from this study. Of these biopsies, 16 showed a heavy infiltrate 26 a moderate, 61 minimal and 121 no eosinophilic infiltrate. No correlation could be found between the degree of infiltrate and age, sex or tumour type. There was some statistically significant correlation between the eosinophilic infiltrate and stromal invasion and/or tumour necrosis. There was a strong statistical correlation between this infiltrate and previous trauma (biopsy) which was supported by the study of bladder biopsies from patients without neoplasms.

Adult↗
PubMed1998

[Ureterocystoplasty--ureteral augmentation of the urinary bladder].

The method of choice in the surgical treatment of neurogenic dysfunctions of the lower urinary pathways is to use the ureteral wall for augmentation of the urinary bladder. The advantage of the method is that it rules out risks and complications encountered in techniques using an excluded intestinal or gastric segment (mucus formation, metabolic disorders, malignant transformation, uroinfection, urolithiasis). The author presents the case-history of a 28-year-old man with a neurogenic bladder due to surgery of meningomyelocele during childhood.

Adult↗
PubMed1992

Detection of blood group surface antigens of urinary bladder tumours using monoclonal antibodies with the avidin-biotin complex technique.

We examined 8 normal bladder transitional epithelia and 65 transitional cell carcinomas of the urinary bladder of various stages and grades for the presence of ABO(H) blood group surface isoantigens using the immunoperoxidase staining via the Avidin-Biotin Complex (ABC) methods. It was found that 27% of patients with grade I tumours, 50% with grade II tumours and 82% with grade III tumours had loss of cell surface isoantigens. When correlated with the clinical stage the tumours showed no surface isoantigens in stage D, while 65% of patients with stage A tumours were positive for surface antigens. From among 37 patients (57%), 28 (43%) survived for more than five years. Our results suggest that surface antigens of transitional cell carcinoma of the urinary bladder tended to disappear as the histologic changes of the tumour progressed. It also was noted that a loss of ABH(O) surface isoantigens was a bad prognostic sign.

ABO Blood-Group System↗
PubMed1979

[The diagnostic value of double-contrast-technique cystography in the evaluation of benign and malignant lesions of the urinary bladder (author's transl)].

Cystography by double-contrast-technique as a simple and quick method of evaluating benign and malignant lesions of the urinary bladder is being described. 301 examinations were reviewed and are being discussed in regard to diagnostic value, indication, complication and radiation exposure of this method. A few typical cases are being demonstrated to illustrate the value of this method in the spectrum of other diagnostic methods in the work-up of urinary bladder lesions.

Contrast Media↗
PubMed1988

Effect of 1-hexylcarbamoyl-5-fluorouracil on development of rat urinary bladder tumor induced by N-butyl-N-(4-hydroxybutyl)nitrosamine.

The present study was conducted to examine the effect of 1-hexylcarbamoyl-5-fluorouracil (HCFU) on the development of urinary bladder tumors induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in rats. One hundred twenty male Fischer 344 rats were divided into 6 groups. Sixty rats (groups 1, 2 and 3) were given 0.05% BBN in drinking water for the initial 8 weeks of the experiment and another 60 rats (groups 4, 5 and 6) served as controls. HCFU mixed in the powder diet was administered at daily doses of 100 mg per kg of body weight. Group 2 received HCFU throughout and group 3 after BBN administration for 8 weeks. All animals were sacrificed at 20 weeks from the beginning of the experiment and examined histopathologically. In groups 1, 2 and 3, urinary bladder tumors developed in 13 of 18, 0 of 20, and 4 of 19, respectively. Incidences of tumors in the 2 groups treated with HCFU were significantly lower than that of group 1 treated with BBN alone. These results indicated that HCFU was effective in suppressing the incidence of bladder tumor.

Animals↗
PubMed1998

AgNORs in benign, borderline and transitional cell neoplasms of the urinary bladder.

Argyrophilic nucleolar organizer regions (AgNORs) were studied in 106 tissue samples from the urinary bladder (6 normal transitional epithelium, 5 cystitis, 12 hyperplastic, 14 dysplastic lesions, 12 carcinoma in situ, 4 transitional cell carcinoma grade 0, 12 grade I, 15 grade II and 12 grade III) to evaluate their role in differentiating benign, borderline and malignant lesions. The NOR counts presented a rising scale from normal (2.21), inflammatory (3.93 for both cystitis and hyperplasia), dysplastic (4.16), carcinoma in situ (5.08) to malignant lesions (5.28 grade I, 6.59 grade II and 8.37 grade III). It was concluded that AgNORs do not have a diagnostic role in these lesions, but that they can act as a reliable adjunct to existing parameters in the early detection of tumour recurrence and grading of malignant neoplasms.

Carcinoma in Situ↗
PubMed1975

New aspects in combined treatment of urinary bladder carcinoma.

To further improve the results of treatment of malignant processes of the urinary bladder, the authors reviewed in detail 420 cases under combined treatment. They found the following results: (1) In 96 (38.4%) out of 250 cases, the cystoscopically normal mucosa distant from the tumour showed histologically definite cancer tissue. (2) The destruction of residual tumour elements by ionising energy after operation depends on the relation between tumour and connective tissue. If there is sufficient connective tissue residual tumours may be destroyed in all probability, otherwise prognosis is poor. (3) In case of tumour cell mass formation in the microspace without active connective tissue, a curative effect by means of ionising energy after operation is not to be exptected, whether there is a multilocular development of carcinoma or not. Surgical treatment has to be extended according to the condition.

Carcinoma in Situ↗
PubMed1997

Characterization of beta-adrenoceptors in urinary bladder: comparison between rat and rabbit.

1. beta-Adrenoceptor subtypes in rat and rabbit urinary bladder were investigated in functional experiments by use of several agonists and antagonists. 2. All agonists tested produced concentration-dependent relaxation, but the relative potencies varied between both species: BRL 37344 (pD2:8.0) > isoprenaline (7.3) > adrenaline (6.7) = noradrenaline (6.6) in rat bladder, and isoprenaline (8.7) = adrenaline (8.5) > noradrenaline (7.7) = BRL 37344 (7.4) in rabbit bladder. 3. The relaxation response to isoprenaline in rat bladder was relatively resistant to propranolol and ICI 118551, and the slopes of Schild plot for both antagonists were different from unity. The apparent pKB values estimated by single concentrations of propranolol (1, 10 microM) and ICI 118551(10 microM) were 6.6 and 5.4, respectively. 4. On the other hand, the relaxation response to isoprenaline in rabbit bladder was antagonized by lower concentrations (1 nM-100 nM) of propranolol and ICI 118551 in a competitive manner, resulting in pA2 values of 8.7 and 8.6, respectively. 5. These results suggest species-heterogeneity of beta-adrenoceptors in urinary bladder; beta 3 and beta 2 subtypes in rat and beta 2 subtype in rabbit.

Adrenergic beta-Agonists↗
PubMed1985

[Treatment of low grade and low stage urinary bladder cancer].

Fifty-seven patients with low-grade and low-stage urinary bladder cancer were treated at our University Hospital between 1970 and 1980. The incidence of low grade and low stage cases was higher in the young group than in the older group, and in male than in female (p less than 0.05). Most of the patients were well-controlled by either TUR or other conservative therapies. The 5-year relative survival rate was 113%. The 5-year actual cumulative recurrence rate after TUR was 63%, whereas, the 5-year actual cumulative recurrence rate was only 35.4% in those who received intravesical instillation therapy and 25% in those who undergone RCH (Radio-Chemo-Hyperthermia) therapy. Five patients (9%) showed an increase of tumor grade from low to intermediate at the time of intravesical recurrence, but no patient showed a change from low to high grade.

Adult↗
PubMed1989

Urinary bladder neoplasms: evaluation with contrast-enhanced MR imaging.

Forty-eight patients with urinary bladder neoplasms were examined with magnetic resonance imaging before and after intravenous administration of gadolinium diethylene-triaminepentaacetic acid (DTPA). Spin-echo sequences with short repetition and echo times were used in all patients; in 20 a gradient-echo technique was used to perform sequential imaging. In 31 patients ratios of tumor signal intensity to that of fat, muscle, and bone marrow were calculated before and after Gd-DTPA enhancement on T1-weighted spin-echo images. Increases in tumor signal intensity on T1-weighted spin-echo images were statistically significant after contrast enhancement (alpha = 1%, P less than .0001). The average rise in relative signal intensity after contrast enhancement was 120% for the tumor-fat ratio (tumor-marrow ratio, 105%; tumor-muscle ratio, 85%). Tumor signal intensity peaked within 120 seconds and remained on a plateau for up to 45 minutes. Necrotic tissue within the tumor, seen in three cases, was detectable only on contrast-enhanced images.

Adult↗
PubMed1975

Kidney and urinary bladder functions of the rainbow trout in Mg and Na excretion.

Magnesium concentration in the urinary bladder of marine teleosts is high and [Na] is low. The inverse relationship may be due to the coupling of Mg secretion to Na reabsorption through a common tubular transport system or coupling may be indirect. Unanesthetized sea-water-adapted Salmo gairdneri were infused with saline or MgCl2, and ureteral urine was collected. Over a wide range of Mg excretion rates, tubular Mg secretion and Na reabsorption show no clear correlation as might be expected from an obligatory tubular Mg/Na exchange. Instead ureteral Mg and Na concentrations and excretion rates are positively correlated. These data are not consistent with the presence of a tubular exchange system. When ureteral urine was allowed to remain in the urinary bladder before being analyzed the inverse relationship between [Mg] and [Na] developed because the bladder reabsorbed Na and H2O, thereby concentrating Mg. Hence, tubular Mg/Na exchanges do not produce the inverse Mg/Na relationship in bladder urine. Instead, Mg is secreted in the nephron, while Na and H2O are reabsorbed from the bladder.

Animals↗
PubMed1994

Rabbit as a model of urinary bladder function.

Micturition is a complex neuromuscular process. Although control mechanisms have been identified at several levels of the central nervous system and spinal cord, the final pathway in the control of micturition is the autonomic innervation of the urinary bladder and related structures. Following this line of reasoning further, micturition is ultimately dependent on the ability of the urinary bladder to both contract and generate intravesical pressure, and to modify its shape in such a way as to efficiently expel its contents without leaving a high residual volume. In order to understand the various elements of micturition, a wide variety of both in vivo and in vitro animal models has been developed. In many cases, animal models have been utilized to describe the effect of specific experimental pathologies on the lower urinary tract. The current review of the use of the rabbit in urological research is not meant to be a comprehensive treatise on the topic, but should provide a rational description of the how this species can be utilized to study both normal and pathological function.

Aging↗
PubMed1984

The value of the DNCB test in bladder cancer. Pretreatment evaluation of immune function and 5-year follow-up of patients with urinary bladder cancer.

In 68 patients with histologically verified tumors of the urinary bladder, cell-mediated and humoral immune parameters were investigated before therapy and the results were re-evaluated after a 5-year observation period in order to correlate them with relapse rate and survival time. Skin test reactivity, as measured with recall antigens (tuberculin, streptokinase-streptodornase, mumps, toxoplasmin and candidin), and serum levels of immunoglobulins do not differentiate between levels of invasion and grade of malignancy. However, it was found that patients with tumors of high grades of invasiveness and malignancy were anergic to the primary skin test antigen dinitrochlorobenzene (DNCB). Furthermore, a correlation between anergic reactivity to the DNCB test and absence of local inflammatory reactions at the tumor site was detected, showing that patients with a negative DNCB challenge test were those in whom no immunocytes could be detected in the intra- and peritumoral area. Survival time and incidence of relapse were also correlated with initial skin test reactivity to DNCB, i.e. all patients with tumor stage pT3 and skin test anergy developed recurrences and died within the 5-year observation period. The correlation between morphological inflammatory criteria and immunological parameters detected in patients with advanced tumor stages should therefore be taken into consideration when taking therapeutic decisions at the time of diagnosis.

Aged↗
PubMed1992

A pharmacological study of NK1 and NK2 tachykinin receptor characteristics in the rat isolated urinary bladder.

1. We have estimated potencies of tachykinin receptor agonist and antagonist analogues in order to determine the recognition characteristics of tachykinin receptors mediating phasic contractile responses of the rat isolated urinary bladder in vitro. 2. The NK1-selective synthetic agonists, substance P methyl ester and GR73632, the synthetic NK2-selective agonists [beta-Ala8]-NKA(4-10) and GR64349, and the mammalian tachykinins, neurokinin A and neurokinin B, were assayed relative to substance P and were found to be approximately equipotent. The NK3-selective agonist, senktide, was inactive (10 microM). 3. Potencies of all these agonists were not significantly different (P > 0.05) when experiments were carried out in the presence of the neutral endopeptidase inhibitor, phosphoramidon, and the kininase II inhibitor, enalaprilat (both 1 microM). 4. The NK1-selective antagonist, GR82334, inhibited responses to substance P methyl ester in a competitive manner in the rat urinary bladder and the rat ileum, and also in the guinea-pig ileum. Markedly different pKB estimates were obtained in the rat bladder (6.38) and rat ileum (6.56) compared to the guinea-pig ileum (7.42). GR82334 (3 microM) was inactive against responses of the rat bladder to [beta-Ala8]-NKA(4-10). 5. The NK1-selective antagonist (+/-)-CP-96,345 also inhibited responses of the rat bladder and guinea-pig ileum to substance P methyl ester; however, in the rat bladder at 1 microM, this antagonist reversibly inhibited responses both to the NK2-selective agonist [beta-Ala8]-NKA(4-10) and to the muscarinic agonist carbachol (P < or = 0.01), thus showing evidence of some non-selective depressant actions. 6. The NK2-selective antagonists, MEN10207 and L-659,874, competitively inhibited responses of the rat bladder to the NK2-selective agonist [P-Ala5]-NKA(4-10) giving pKB estimates of 5.75 and 6.68,respectively. Both antagonists (1O microM) were inactive against responses to the NKI-selective agonist substance P methyl ester.7. These results support the proposal of a mixed population of NKI and NK2 receptors mediating contraction of the rat isolated urinary bladder. The NK2 receptor is characterized by a relatively low affinity for the NK2-selective antagonist MEN10207 but a high affinity for L-659,874. The NKImediated responses are inhibited by (+/-)-CP-96,345: this compound however, has non-specific depressant effects in the rat bladder at high concentration (1 microM). In contrast, the NK,-receptor peptide antagonist GR82334, did not have non-specific depressant effects and competitively inhibited NK, responses in the rat bladder and rat ileum with an affinity significantly lower than at the NK,-receptors in the guinea-pigileum.

Animals↗
PubMed1989

The effect of cromakalim on the smooth muscle of the guinea-pig urinary bladder.

1. The actions of cromakalim were studied on the detrusor muscle from guinea-pig urinary bladder. Cromakalim reduced the frequency and amplitude of spontaneous contractile activity of the smooth muscle of the guinea-pig urinary bladder at 5 x 10(-8)M and abolished the activity at concentrations above 5 x 10(-7)M. 2. Electrophysiological experiments demonstrated that cromakalim increased membrane conductance, caused a dose-dependent hyperpolarization of the cell membrane and loss of spike activity. These events are consistent with the opening of K+ channels. 3. The effects of 10(-6)M and 10(-5)M cromakalim on the contractile responses to carbachol, potassium and transmural nerve stimulation were studied. Cromakalim did not prevent the detrusor from responding to these agents, although it significantly reduced the contractile response to K+ at concentrations below 70 mM. 4. Uptake and efflux experiments using 86Rb+ were unable to demonstrate any significant effect on transmembrane movement produced by cromakalim (10(-5)M). 5. 43K+ efflux showed a dose-dependent increase in the rate constant on addition of cromakalim. The difference in the selectivity for K+ over Rb+ was confirmed in dual label uptake experiments. 6. Substitution experiments in which the K+ ions in the tissue were gradually replaced by Rb+ demonstrated that cromakalim had a progressively decreasing effect on spontaneous activity as internal K+ was lowered. When all the K+ was replaced by Rb+, cromakalim no longer inhibited spontaneous activity, confirming that the channel opened by cromakalim appears relatively impermeant to Rb+.

Animals↗
PubMed1980

Release of prostaglandin E from the isolated urinary bladder of the guinea-pig.

1 Release of prostaglandin E (PGE) from guinea-pig urinary bladder in vitro has been demonstrated both in the resting state and during electrical stimulation. 2 The electrically evoked release of PGE was significantly higher than the resting release and was frequency-dependent. 3 The released substance was characterized as PGE pharmacologically by (a) blockade of its response by SC-19220 on guinea-pig ileum, (b) reduction of the amount of the released substance by indomethacin and (c) the inhibitory effect of the released substance on adrenergic neurotransmission in guinea-pig vas deferens. 4 The prostaglandin seemed to originate from the muscle since tetrodotoxin treatment did not abolish the release during direct muscle stimulation; however, concomitant release from neuronal tissue could not be excluded in the present experiments. 5 Indomethacin failed to inhibit the mechanical responses of the bladder to transmural stimulation. 6 The present experiments suggest that PGE is not involved in mediating the non-cholinergic non-adrenergic neurotransmission in the guinea-pig urinary bladder.

Animals↗