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Tissue-engineered urinary bladder wall using PLGA mesh-collagen hybrid scaffolds: a comparison study of collagen sponge and gel as a scaffold.

PURPOSE: Tissue engineering of the urinary bladder using autologous cells and biodegradable scaffold is a promising method for augmentation. The authors developed 2 hybrid scaffolds by combining poly (DL-lactic-co-glycolic acid; PLGA) mesh for mechanical strength with collagen sponge or gel suitable for cell seeding. The aim of this study was to compare collagen as a scaffold between collagen sponge and gel and to construct a tissue-engineered urinary bladder wall utilizing these hybrid scaffolds. METHODS: The PLGA mesh-collagen hybrid scaffolds were prepared by introducing collagen sponge or gel into the PLGA knitted mesh. Urothelial and smooth muscle cells were obtained from porcine urinary bladder wall and were cultured in their respective media. The cells were seeded on these hybrid scaffolds. These constructs were analyzed morphologically and immunohistochemically. RESULTS: The urothelial layer was generated 3 dimensionally by culturing urothelial cells with PLGA mesh and collagen sponge. The smooth muscle layer was constructed by culturing smooth muscle cells with PLGA mesh and collagen gel. And a novel tissue-engineered urinary bladder wall was constructed laminating the urothelial and smooth muscle layers. CONCLUSIONS: Ex vivo construction of urinary bladder wall using hybrid scaffolds prepared by combining PLGA mesh with collagen sponge or gel was successful. This tissue-engineered urinary bladder wall allows easy handling and may become a promising tool for bladder augmentation.

Absorbable Implants↗

Effect of vitamin A acetate on urinary bladder carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine in rats.

The effect of vitamin A acetate on the urinary bladder carcinogenicity of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was determined in male Wistar rats. Vitamin A acetate at the dose administered induced no changes in the urinary bladder or other organs when administered without the carcinogen. However, hypervitaminosis A inhibited keratinization and squamous metaplasia in bladder lesions induced by BBN, and the incidence of transitional cell carcinoma and papilloma of the urinary bladder was significantly reduced at a dose greater than 100 IU/g diet (P less than 0.02). The present experiment suggests that for the urinary bladder epithelium of rats hypervitaminosis A reduced susceptibility to the tumorigenicity of BBN.

Animals↗

Diagnosis of urinary bladder rupture using ultrasound contrast cystography: in vitro model and two case-history reports.

Because urinary bladder rupture can be life threatening, a simple, safe technique for evaluating patients is desirable. Current diagnostic protocols involve radiographic imaging, but ultrasound-based contrast techniques have not been methodically evaluated in veterinary patients with urologic trauma. Ultrasound contrast cystography (contrast cystosonography) involves infusion of microbubbled saline solution through a urinary catheter. It was performed in an in vitro model and in 2 dogs with naturally occurring urinary bladder rupture. A positive result consisted of visualizing microbubbles sonographically in fluid surrounding the bladder immediately after infusion of contrast into the urinary catheter. A positive result was obtained both in the in vitro model and in the 2 dogs, with radiographic and surgical confirmation of naturally occurring intraperitoneal urinary bladder rupture in the dogs. Based on the results of this study, ultrasound contrast cystography appears to be more sensitive than two-dimensional (2D) abdominal sonography for detecting naturally occurring urinary bladder rupture in dogs.

Animals↗

Induction of tumors of the urinary bladder in female mice following surgical implantation of glass beads and feeding of bracken fern.

The carcinogenic effect of bracken fern (Pteris aquilina) to the urinary bladder of mice was studied. Powdered bracken fern mixed with a basic commercial diet (1:4 by weight) was fed to a group of 40 ICR strain mice for 20 weeks after the implantation of a glass bead into the bladder. A total experimental period was 70 weeks. Fifteen mice survived 40 or more weeks and 4 mice (27%) developed urinary bladder tumors. No urinary bladder tumor was found in the group of mice fed a similar bracken fern diet mixture without a glass bead in their bladder and in the control group of mice fed a normal diet after the implantation of a glass bead. The result of this experiment may indicate that there is a metabolite(s) in the urine of bracken-fed mice carcinogenic to the bladder.

Animals↗

The effects of catechol on the urinary bladder of rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine.

The effect of catechol on the development of urinary bladder tumors in Fischer rats treated with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was studied. A solution of 0.05% catechol and 0.001% BBN was administered in the drinking water ad libitum for 78 weeks. The urinary bladders were then removed and examined microscopically. No statistically significant difference was observed between the experimental group receiving 0.001% BBN with 0.05% catechol and animals receiving 0.001% BBN alone with respect to the incidence of hyperplasia, papilloma, or carcinoma of the urinary bladder. Animals receiving 0.05% catechol alone in the drinking water had no macroscopic or microscopic lesions significantly different from those in control animals receiving tap water. Analyses of the urine of animals receiving catechol in their drinking water indicated that greater than 99% of the catechol present was in the form of either glucuronide or sulfate conjugates. In a second bioassay, the potential cocarcinogenicity of catechol, administered together with BBN, was explored by direct instillation into the urinary bladder. The development of calculi and possible infections of the urinary tract within all groups of treated animals suggests that this bioassay technique for cocarcinogenicity is of questionable value. These data show that catechol at the dose and mode of administration employed in this study did not affect the epithelium of the urinary bladder or enhance the carcinogenic activity of BBN.

Animals↗

Dynamic multi-planar EPI of the urinary bladder during voiding with simultaneous detrusor pressure measurement.

Magnetic resonance imaging gives high quality images of the urinary bladder with excellent contrast. We report here the first application of dynamic, multi-slice, echo planar imaging to a study of urinary bladder emptying. Changes in urinary bladder volumes and rates of urine expulsion from the bladder have been measured simultaneously with bladder pressure. The method shows promise for clinical applications involving compromised bladder function, for reappraising bladder contraction strength-volume relationships, and for investigating the rate of change of length, three-dimensional shape, and wall tension in different parts of the bladder during micturition.

Echo-Planar Imaging↗

The effects of lithium, indomethacin, and neomycin on vasopressin-induced contractions in rat urinary bladder.

1. [Arg8]Vasopressin (AVP) induced a contraction response in rat urinary bladder smooth muscle in a dose-dependent manner. 2. Indomethacin in a 10-microM concentration cannot change the effects of AVP on urinary bladder smooth muscle, which seem to be mediated by a direct action on the muscle rather than indirectly through prostanoid release. 3. Lithium (0.5, 1, and 10 mM) made the muscle more sensitive to AVP action. 4. Neomycin (1.25, 2.5, and 5 mM) had an inhibitory effect on AVP-induced contraction. 5. It seems that in rat urinary bladder vasopressin-induced contraction is mediated through phosphoinositide metabolism.

Animals↗

Significance of overexpression of metallothionein in mouse urinary bladder focal lesions induced by treatment with N-butyl-N-(4-hydroxybutyl)-nitrosamine.

Metallothionein (MT) is expressed in various types of human tumors, including transitional cell carcinomas of the urinary bladder, but its biological significance remains unclear. In the present study, the role of MT in urinary bladder carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) treatment was investigated using C57BL/6 mice. One hundred 5-week-old male C57BL/6 mice were divided into two groups, which were given drinking water with or without 0.05% BBN throughout the experimental period. Subgroups of ten animals from each group were sacrificed at weeks 5, 10, 15, 20 and 25, and urinary bladder samples were examined immunohistochemically for MT, proliferating cell nuclear antigen (PCNA) and apoptosis. MT was found to be abundant in normal-looking mucosa, but decreased with progression from precancerous lesions to invasive carcinoma in the urinary bladder obtained from BBN-treated mice. Lesions could be divided into MT-positive and negative. There was a tendency for greater MT expression in PCNA-positive lesions, while apoptosis was rather associated with MT-negativity. These data suggest that the overexpression of MT may play a role in mouse urinary bladder carcinogenesis.

Animals↗

Pharmacological and molecular biological evidence for ETA endothelin receptor subtype mediating mechanical responses in the detrusor smooth muscle of the human urinary bladder.

The aim of this study was to characterize endothelin receptor subtypes of the detrusor muscle of the human urinary bladder. The receptor subtypes mediating endothelin (ET)-1-induced activity in the human detrusor smooth muscles have been characterized using isometric contraction and reverse transcription-polymerase chain reaction (RT-PCR). ET-1 (a non-selective ET receptor agonist; 10(-10) M to 10(-6) M) exhibited concentration-dependent contractions in human urinary bladder with a plateau at concentrations above 3x10(-7) M. Neither IRL1620 nor sarafotoxin S6c (both ETB-selective agonists; 10(-10) M to 10(-6) M) elicited contractile activity in the human urinary bladder detrusor smooth muscle. FR139317 (an ETA-selective antagonist; 10(-7) M to 10(-5) M) produced a marked shift to the right of the ET-1 concentration-response curve in human urinary bladder detrusor smooth muscle (from the Schild plot TpA2=7.96; slope=0.95). In contrast, RES701-1 (an ETB-selective antagonist; 10(-7) M to 10(-5) M) had no effect on the ET-1 concentration-response curve. RT-PCR revealed positive amplification of ETA receptor mRNA fragment, but not ETB. These results indicate that the ET-1-induced contractile effects of urinary bladder detrusor smooth muscle seem to be mediated mainly by the ETA receptor, not by the ETB receptor.

Aged↗

Inhibitory mechanism of BRL37344 on muscarinic receptor-mediated contractions of the rat urinary bladder smooth muscle.

We examined the inhibitory mechanism of BRL37344, a beta-adrenoceptor agonist that is considered to be specific to beta(3)-subtype, on muscarinic receptor-mediated contraction of the rat urinary bladder smooth muscle. BRL37344 produced apparently biphasic concentration-relaxation curves in the urinary bladder smooth muscle contracted with carbachol (0.6 microM). The first and second phases had estimated p D(2) (-logEC(50)) values of 7.80+/-0.34 and 4.62+/-0.18, respectively ( n=6). The first component of the BRL37344 concentration-response curve was not affected by propranolol (1 microM), whereas it was inhibited by higher concentrations of the drug (10 microM or 30 microM). The second component was completely resistant to propranolol. On the other hand, BRL37344 produced monophasic concentration-relaxation of 30 mM KCl-precontracted urinary bladder smooth muscle with a p D(2) value of 8.34+/-0.18 ( n=6). Pretreatment of the urinary bladder smooth muscles with BRL37344 (30, 100 and 300 microM) significantly ( P<0.05) shifted the concentration-response curves for carbachol-induced contractions. In radioligand binding experiments, BRL37344 concentration-dependently displaced the specific binding of [(3)H] N-methyl scopolamine to muscarinic receptors on rat urinary bladder smooth muscle membranes. Additionally, BRL37344 inhibited [(3)H] N-methyl scopolamine binding to cloned human muscarinic receptors (M(1)-M(5)) expressed in Chinese hamster ovary cells. These results suggest that BRL37344 attenuates muscarinic receptor-mediated contractions through prevention of the agonists binding to their receptors, in addition to stimulation of beta(3)-adrenoceptors, in rat urinary bladder.

Adrenergic beta-Agonists↗

Urinary bladder lesions induced by persistent chronic low-dose ionizing radiation.

The incidence of urinary bladder cancer in the Ukraine increased from 26.2 to 43.3 per 100,000 population between 1986 and 2001 after the Chernobyl accident. The present study was conducted to evaluate the development of radiation-dependent lesions in the urinary bladders of people living in cesium 137 ((137)Cs) radio-contaminated areas of the Ukraine. Bladder urothelial biopsies from 159 male and 5 female patients were subjected to histological examination and immunohistochemical study of p38 mitogen-activated protein kinase (MAPK), as well as the p50 and p65 subunits of nuclear factor kappa B (NF-kappa B). A pattern of chronic proliferative atypical cystitis accompanied with large areas of sclerosis of connective tissue in the lamina propria was commonly observed in all cases. Interestingly, these lesions were associated with a dramatic increase in the incidences of dysplasia/carcinoma in situ, and, moreover, small urothelial carcinomas were incidentally detected. We defined the overall condition as "Chernobyl cystitis." Greatly elevated levels of p38, p65 and p50 expression in the urothelium were evident and the patients showed increased (137)Cs in urine. The data support conclusions from our previous studies of a critical role for increased oxidative stress in generation of urinary bladder urothelial lesions in individuals chronically exposed to low-dose (137)Cs radiation. Alterations in the p38 MAPK cascade and accumulation of NF-kappa B subunits could be crucial early molecular events in the pathogenesis of Chernobyl cystitis.

Adult↗

The effect of distension of the urinary bladder on left ventricular inotropic state in anesthetized dogs.

To decide whether distension of the urinary bladder reflexly affects the left ventricular inotropic state, experiments were performed in eight dogs anesthetized with pentobarbitone. After cannulation of both ureters the urinary bladder was repeatedly distended through a urethral catheter with warm Ringer solution at a steady intravesical pressure. The maximal rate of rise of left ventricular pressure (dP/dtmax) obtained at constant heart rate and cardiovascular pressures was used to assess changes in left ventricular inotropic state. Arterial blood pressure was prevented from changing by a pressurized reservoir containing warm Ringer solution and connected to the femoral arteries. Following prevention of the reflex increase in heart rate by atrial pacing, distension of the urinary bladder always increased the maximal rate of rise of left ventricular pressure in the eight dogs. There were no significant changes in left ventricular systolic or end-diastolic pressures. The increase in maximal rate of rise of left ventricular pressure was abolished following the administration of propranolol. The results indicate that a reflex increase in left ventricular inotropic state occurred in response to distension of the urinary bladder. This reflex response involved beta-adrenergic stimulation.

Animals↗

Overexpression of cyclooxygenase-2 in squamous cell carcinoma of the urinary bladder.

Epidemiological studies indicate that the development of squamous cell carcinoma of the urinary bladder is closely associated with chronic inflammation of the urinary tract, but the underlying mechanism is unknown. Cyclooxygenase (COX)-2 is involved in tumorigenesis in many tumors. The purpose of this study was to investigate the role of COX-2 in squamous cell carcinoma of the urinary bladder by immunoblot and immunohistochemical analyses. COX-2 protein was undetectable in normal bladder samples, but was expressed in 29 of 29 (100%) squamous cell carcinomas and in 8 of 8 (100%) squamous metaplasias. The expression of COX-2 showed intense, homogenous cytoplasmic immunostaining in squamous cell carcinomas. In contrast, COX-2 was heterogeneously expressed in 6 of 12 (50%) cases of transitional cell carcinoma of the bladder combined with squamous cell carcinoma, consistent with previous findings. We provide the first evidence that COX-2 is expressed in squamous cell carcinomas of the urinary bladder and in the precursor lesions, indicating its involvement in the development of this type of malignancy.

Aged↗

Extracellular Ca2+ controls outward rectification by apical cation channels in toad urinary bladder: patch-clamp and whole-bladder studies.

Outward rectifying, cation channels were observed in the epithelial cells of the urinary bladder of the toad. Bufo marinus. As studied in isolated cells using the patch-clamp technique, the channel has an average conductance of 24 and 157 pS for pipette potentials between 0 and +60 mV and -60 to -100 mV, respectively, when the major cation in both bath and pipette solutions is K+. The conductance of the channel decreases with increasing dehydration energy of the permeant monovalent cation in the order Rb+ = K+ greater than Na+ greater than Li+. Reversal potentials near zero under biionic conditions imply that the permeabilities for all four of these cations are similar. The channel is sensitive to quinidine sulfate but not to amiloride. It shares several pharmacological and biophysical properties with an outwardly-rectifying, vasopressin-sensitive apical K+ conductive pathway described previously for the toad urinary bladder. We demonstrate, in both single-channel and whole-bladder studies, that the outward rectification is a consequence of interaction of the channel with extracellular divalent cations, particularly Ca2+, which blocks inward but not outward current. Various divalent cations impart different degrees of outward rectification to the conductive pathway. Concentrations of Mg2+ and Ca2+ required for half-maximal effect are 3 X 10(-4) and 10(-4) M, respectively. For Co2+ the values are 10(-6) M at +50 mV and a 10(-4) M at +200 mV. The mechanism of blockade by divalent cations is not established, but does not seem to involve a voltage-dependent interaction in which the blocker penetrates the transmembrane electric field. In the absence of divalent cations in the mucosal solution, the magnitudes of inward current carried by Rb+, K+, Na+ and Li+ through the apical K+ pathway at any transepithelial voltage, are in the same order as in the single-channel studies. We propose that the cation channel observed by us in isolated epithelial cells is the single-channel correlate of the vasopressin-sensitive apical K+ conductive pathway in the toad urinary bladder and is also related to the oxytocin- and divalent cation-sensitive apical conductivity observed in frog skin and urinary bladder.

Animals↗

Propantheline and in vitro reactivity of urinary bladder smooth muscle in guinea pigs.

OBJECTIVE: The aim of this study was to verify the in vitro action of propantheline on urinary bladder smooth muscle in guinea pigs and to compare its effect with previously tested oxybutynin. MATERIALS AND METHODS: The reactivity of the urinary bladder smooth muscle was estimated in vitro using organ chambers. The smooth muscle strips were prepared from guinea pig urinary bladders and aerated under the tension in Krebs-Henseleit's solution in the organ bath. The cumulative concentration-response curves to acetylcholine (10(-8)-10(-3) mol.l(-1)) were constructed before and after 15 minute incubation with propantheline in concentration of 10(-6), 10(-5), 10(-4), and 10(-3) mol.l(-1). RESULTS: Propantheline caused a decrease of urinary bladder smooth muscle reactivity to acetylcholine. This decrease was statistically significant only at concentration of 10(-5), 10(-4) and 10(-3) mol.l(-1) of propantheline. CONCLUSIONS: Propantheline significantly influenced the reactivity of urinary bladder smooth muscle to acetylcholine in guinea pigs. Comparing the influence of oxybutynin we can conclude that oxybutynin caused a significantly higher decrease of the reactivity to acetylcholine than propantheline. (Fig. 3, Ref. 30.)

Acetylcholine↗

Exploring the Genetic Landscape of Primary Marginal Zone Lymphoma of the Urinary Bladder.

Extranodal marginal zone B-cell lymphoma (MZL) of mucosa-associated lymphoid tissue is the most frequent primary lymphoma of the urinary bladder. Although MZLs from various anatomical sites are often associated with autoimmune disorders, infections, and site-characteristic genetic alterations, the molecular foundations and potential infectious triggers of urinary bladder MZL remain poorly understood. To elucidate the disease etiology and correlation with MZLs arising in other locations, we examined a cohort of 17 cases (11 women and 6 men) diagnosed with primary bladder MZL between 2005 and 2025. Immunohistochemical analysis confirmed the literature, with all samples testing positive for the pan B-cell markers CD20 and CD79a and negative for CD5 (except 1), cyclin D1, and SOX11. Thirteen samples exhibited secretory differentiation and displayed immunoglobulin light chain restriction (9 &#x3ba; and 4 &#x3bb;). No gene rearrangements in BCL2, BCL6, BCL10, IRF4, MALT1, and MYC were detected. High-throughput sequencing identified 31 pathogenic/likely pathogenic somatic mutations across 18 genes, with TBL1XR1 (n = 8), MAP2K1 (n = 4), and TNFAIP3 (n = 2) being the most frequently mutated ones. Additionally, all cases included variants of unknown significance. The sample of 1 patient tested positive for Chlamydia trachomatis, human betaherpesvirus 6B, and Epstein-Barr virus. Escherichia coli was detected in 5 samples. We provide compelling evidence that urinary bladder MZL is a point mutation-driven disease rather than gene fusion-driven disease and that E coli is present in approximately one-third of tumor biopsies. These tumors frequently harbor pathogenic mutations in genes encoding components regulating plasma cell differentiation and the pleiotropic MAPK/ERK signaling pathway. TBL1XR1, which was unexpectedly frequently mutated, is generally linked to more aggressive variants of MZL and diffuse large B-cell lymphoma; however, its prognostic significance in urinary bladder MZL remains to be determined. Comparative analysis highlighted partial overlap of urinary bladder MZL mutational profiles with those found in salivary gland MZL.

Humans↗

Immunodetection of androgen receptor in human urinary bladder cancer.

We investigated the expression of androgen receptor (AR) protein in transitional cell carcinoma of human urinary bladder in paraffin-embedded sections of tumours obtained from nine patients with urinary bladder cancer treated by radical cystectomy. In addition, immunoblotting of AR was also performed on selected samples. Nuclear immunoreactivity of AR was found in seven of the nine urinary bladder cancers studied. AR showed variable staining intensity within a tumour. In the immunoblots, a 110 kDa AR signal was seen with anti-AR antibody, and faint bands of 90 and 60 kDa were also observed. Immunohistochemistry of p53 and c-erbB-2 was also carried out and compared with the distribution of AR. The high frequency of AR expression suggests a role for androgens in transitional cell carcinoma of human urinary bladder.

Adenocarcinoma↗