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Influence of chitosan and polycarbophil on permeation of a model hydrophilic drug into the urinary bladder wall.

Influence of dispersions of mucoadhesive polymers chitosan and polycarbophil on permeability properties of urinary bladder was investigated in vitro on isolated porcine urinary bladder. Pipemidic acid as a model hydrophilic drug was used. Its distribution in the bladder wall was determined from actual tissue concentrations by a method based on sectioning of frozen tissue and extraction of tissue slices. Pipemidic acid tissue concentration versus tissue depth profiles were evaluated by a diffusion model assuming constant diffusion coefficient. Increase in bladder wall permeability was observed in the presence of both polymers. Apparent permeability (mean+/-S.D.) of urinary bladder wall was increased 2.7+/-2.9 and 2.8+/-2.0 times for chitosan, and 2.3+/-2.0 and 4.3+/-4.2 times for polycarbophil at 0.5 and 1.0%, w/v polymer concentration, respectively. This increase is a consequence of the increased permeability of urothelium. These findings support investigations on application of chitosan and polycarbophil in development of mucoadhesive intravesical drug delivery systems. Experimental model may be applied to evaluate the results of experiments with drugs used in intravesical therapy.

Acrylic Resins↗

[Hemodynamics in the territory of balloon occluded internal iliac artery--problems of balloon occluded arterial infusion therapy for urinary bladder cancer].

Balloon occluded arterial infusion therapy (BOAI) with anticancer drugs has been performed widely for urinary bladder cancer. It is expected that a dense anticancer drug would perfuse the territory of the vesical arteries under occlusion of the bilateral internal iliac arteries. In balloon occluded internal iliac arteriography, however, contrast media are gradually washed out in spite of complete occlusion of the bilateral internal iliac arteries. This washout process takes place via collateral flow to the acute occlusion and varies according to the position of occlusion and arterial variations in branching. We wondered whether anticancer drug administered by BOAI would perfuse the territory of the vesical arteries as expected. We analyzed the washout process of balloon occluded internal iliac arteriography in 41 patients with urinary bladder cancer in whom preoperative BOAI had been performed. We estimated the hemodynamics and perfusion of the anticancer drug to the urinary bladder on the basis of analysis of balloon occluded internal iliac arteriography in each case. Perfusion scintigraphy and histological examination of surgical specimens of urinary bladder cancer (21 cases) confirmed the validity of our estimates. In some cases it was presumed that the anticancer drug did not reach the territory of the vesical arteries.

Adult↗

Mucinous (colloid) carcinoma of urinary bladder following long-term cyclophosphamide therapy for Waldenstrom's macroglobulinemia.

Carcinoma of the urinary bladder is a known complication of cyclophosphamide therapy. Almost all such cases have been transitional cell carcinomas. We report here the second example of an adenocarcinoma of bladder and the first purely mucinous (colloid) carcinoma of urinary bladder developing after long-term cyclophosphamide therapy. The patient, a 77-year-old woman, had been treated for Waldenstrom's macroglobulinemia for at least 24 years, during which time treatment for this disease varied from 50 to 100 mg per day. The disease terminated in acute myelogenous leukemia, and she died of severe disseminated intravascular coagulopathy associated with hypermacroglobulinemia. The mucinous (colloid) carcinoma of the urinary bladder was an incidental finding at autopsy.

Adenocarcinoma, Mucinous↗

[Biocompatibility of acellular urinary bladder submucosa].

OBJECTIVE: To investigate the biocompatibility of acellular urinary bladder submucosa (AUBS). METHODS: The acellular collagen matrix of human urinary bladder submucosa was developed using freeze-thawed enzymatic treatment and freeze-drying technique. Human oral keratinocytes were cultured and seeded on AUBS at a density of 2 x 10(6)/ml in vitro. The proliferation of the cells were observed. Pockets were created in the abdominal muscle wall of 18 SD rats. AUBS in size 1 cm x 1 cm was implanted into the pocket. The grafts were observed by light microscope 3, 6, 10, 14, 21 and 28 days after operation. RESULTS: AUBS mainly consisted of collagen fibers with a three-dimensional network structure. After the oral keratinocytes were seeded, continuous oral epithelium layer was formed on the surface of AUBS after 10 days in vitro. Histological observation of the grafted AUBS showed progressive cell infiltration at 6 days. New capillaries formed at 14 days. The collagen fibers arranged regularly at 28 days after implantation. CONCLUSION: Freeze-dried AUBS may be used as a suitable scaffold for tissue regeneration, which can induce cell proliferation both in vivo and in vitro and has good biocompatibility.

Animals↗

The lymphatic vessels and their relationship to lymph formation in the human urinary bladder.

After endoscopic transurethral biopsies of normal human urinary bladder, an extensive network of small initial lymphatic vessels was depicted by means of light and electron microscopy. Using light microscopy, lymphatic vessels were seen in the mucosa and submucosa and formed a complex network in the detrusor muscular coat. These lymphatics were characterized by an irregular and attenuated wall and increased in number and size from the superficial to the deeper region of the bladder. Ultrastructurally, the lymphatic wall was characterized by endothelial cells joined together end-to-end or by complicated interdigitations. Often intercellular channels and gaps between two contiguous endothelial cells were present. A broad network of elastic and collagen fibers joined the lymphatic endothelial wall to the neighboring connective tissue. Nevertheless, as far as the fibrillar component was concerned, the vesical intramuscular lymphatic endothelial wall lacked elastic fibers. These anatomic variations were examined in reference to lymph formation in an organ (the urinary bladder) which undergoes continual changes in volume and pressure.

Adult↗

Histologic changes in the urinary bladder in relation to cigarette smoking and use of artificial sweeteners.

A total of 6503 sections of urinary bladder epithelium from 282 subjects were examined in random order, and histologic alterations, particularly the number of cell rows and the presence and extent of cells with atypical nuclei, were recorded. Cases were either individuals who had never smoked or who had smoked cigarettes. Microscopic slides with cells having 50% or more atypical nuclei were found in 4.3% of those who had never smoked; 67.1% in those who had smoked less than 20 cigarettes a day; 82.3% in those who had smoked 20 to 39 cigarettes a day; and 88.4% of the 40 or more a day cigarette smokers. The percentage of slides with six or more cell rows in these groups were 4.8%, 52.2%, 62.5%, and 72.9%, respectively. The histologic findings in the urinary bladder in relation to smoking habits fully complement the epidemiologic studies showing a dose-response of cigarette smoking and urinary bladder cancer. No relationship was found between changes in the urinary bladder epithelium and the use of artificial sweeteners.

Adolescent↗

Changes in cholinergic innervation and neuropharmacologic properties in idiopathic hypotonic urinary bladders.

Tissue specimens from hypotonic and normotonic human urinary bladders were investigated histochemically, chemically and neuropharmacologically. In hypotonic bladders the density of acetylcholinesterase (AChE)-positive nerves was markedly reduced and the nerve AChE staining intensity was weak. The concentration of acetylcholine was significantly lower than in specimens from normotonic bladders. At field stimulation the contractions were weak. The observations indicated that sparse cholinergic innervation and reduced acetylcholine synthesis are important for the impaired contractility in idiopathic dystonic bladder.

Acetylcholine↗

[A case of squamous cell carcinoma of the urinary bladder associated with bladder calculi].

A case of squamous cell carcinoma of the urinary bladder associated with a bladder stone in a 43-year-old man is reported. Because a 1 cm x 1 cm sized mass was found in the right lateral side of the dome at the time of vesicolithotomy, partial cystectomy was performed. The weight of the stone was 285 g and the tumor was histologically diagnosed as squamous cell carcinoma, grade 2, pT2. Radical cystectomy with ileal conduit was sandwiched by a total of 6 cycles of chemotherapy with PVB. Twelve cases of squamous cell carcinoma of the urinary bladder associated with a bladder stone(s) from the Japanese literature are reviewed, and the relationship between bladder stone, leukoplakia and squamous cell carcinoma discussed.

Adult↗

Urinary bladder cancer and the petroleum industry: a quantitative review.

PURPOSE: To estimate the pooled risk of petroleum industry for urinary bladder cancer. MATERIAL AND METHODS: All observational studies that evaluated the association between urinary bladder risk and the petroleum industry were reviewed. We have only identified eight case-control studies. These studies were carried out between 1989 and 1995. RESULTS: Of the eight localized studies six were exclusively for males. The other two studies included both males and females, but none reported separately the risk among men and women. There was an obvious risk of petroleum industry in the pooled risk (odds ratio 1.4, 95% confidence interval (CI) 1.27-1.54). Also, Q test was not significant (P>0.1), denoting homogeneity across the pooled studies. Pooled analysis applying the random effect model was 1.50 (95% CI 1.29-1.75). CONCLUSION: Although our pooled estimate shows that the petroleum industry is associated with the risk of urinary bladder cancer, the eight studies were based on retrospective data from case-control studies. Further prospective studies evaluating the association between petroleum industry and urinary bladder cancer risk are strongly needed.

Case-Control Studies↗

[Diagnosis and treatment of locally advanced cancer of the urinary bladder].

The term "locally advanced cancer of the urinary bladder" is discussed. The data on examination and treatment of 375 patients are presented to work out criteria of diagnosis of the disease. Such patients have been shown to reveal extensive lesions from bladder tumor coupled with such homeostatic disorders as hypoamino-acidemia, endotoxicosis, metabolic acidosis, immunity deficiency and disturbed hemoglobin-mediated transport of oxygen. Early postoperative complication incidence can be cut by 30-47% and 3-year survival after cystectomy-increased by 19% provided said homeostatic disturbances are corrected and immuno- and biostimulation is carried out. The best results in the treatment of locally advanced urinary bladder cancer (T2(m)N0M0) were recorded among cases of organ-saving therapy-65-70% have survived 5 years. Only 36.4% of patients with tumor (T3abN0M0) who received complex treatment (cystectomy + preoperative homeostatic correction) have survived 5 years. None of the patients with tumor (T4N0M0) has survived 3 years; therefore, only radiation and chemotherapy should be recommended in such cases.

Humans↗

Unsuccessful effort to detect human papillomavirus DNA in urinary bladder cancers by the polymerase chain reaction and in situ hybridization.

The association of human papillomavirus (HPV) with urinary bladder carcinogenesis is now a controversial issue. In order to certify the presence of HPV DNA in urinary bladder cancers, the polymerase chain reaction (PCR) using five primer sets for detecting various HPV types was used in this study as well as in situ hybridization (ISH) for HPV 16 and 18 detection. In the PCR study of 93 DNA samples extracted from formalin-fixed and paraffin-embedded urinary bladder cancers, no HPV DNA was detected in these tumor samples. The ISH study was also performed on the same tumor samples, but failed to demonstrate any HPV 16- or 18-positive signals in all except one of the tumor samples. However, the PCR failed to demonstrate HPV 16 DNA even in the bladder cancer positive for HPV 16 DNA by the ISH. This ISH technique was able to demonstrate HPV 16 and 18 DNA in eight of 13 paraffin-embedded cervical cancers, in which HPV 16 or 18 DNA had already been detected by the PCR. Our HPV study using PCR and ISH revealed that the HPV status of urinary bladder carcinomas was far different from that of cervical cancers.

DNA Probes, HPV↗

Combination radiotherapy of urinary bladder carcinoma with chemohyperthermia.

The combination therapy of urinary bladder cancer with radiation and hyperthermia with bleomycin was investigated. Immediately following daily external irradiation (40 Gy/4 weeks), patients were irrigated with a solution of warmed saline (intravesical temperature, 42-43 degrees C) containing 30 micrograms/ml bleomycin. Of a total of 56 patients, complete responses were observed in 25, and partial responses in 21. Among T2-T3 cases, an 84% response rate was noted in combination therapy, whereas a 56% response rate was observed after radiation alone (50-70 Gy). The side-effects of the combination therapy were limited to reversible bladder irritation, and bladder capacity could be maintained within normal limits. These results suggest that combination therapy represents an effective conservative therapy for the management of bladder cancer.

Administration, Intravesical↗

Electroporation-mediated muscarinic M3 receptor gene transfer into rat urinary bladder.

BACKGROUND: Muscarinic M3 (M3) receptor has been recognized as a major muscarinic receptor for smooth muscle contractions of the urinary bladder. Under the hypothesis that overexpression of M3 receptor in the urinary bladder would enhance urinary bladder contractions, we have transferred the M3 receptor gene into rat bladders using electroporation (EP) and evaluated the functional expression of the transferred gene. METHODS: Plasmids expressing luciferase, a green fluorescence protein and M3 receptor were injected into the rat bladder and square-wave electric pulses were immediately applied. Two days after gene transfer, we analyzed gene expression. Immunohistochemical staining was performed and the contractile responses from isolated bladder strips, which were induced KCl, carbachol and electrical field stimulation (EFS), were evaluated. RESULTS: The optimal conditions of electroporation were 8 pulses, 45 voltages, 50 milliseconds/pulses and 1 Hz. Under these conditions, luciferase gene expression was enhanced approximately 300-fold, compared to an injection of DNA only. Regarding immunohistochemistry with an anti-M3 receptor, an increase in immunoactivity was observed in the M3 receptor gene transferred rat bladder, compared to the bladder of the control rat. In rats with the transferred M3 receptor gene, carbachol- and EFS-induced maximum contractile responses of bladder smooth muscle strips significantly increased. CONCLUSIONS: These findings suggest that an in vivo EP procedure is an useful method for gene transfer into the bladder and that an overexpression of M3 receptor in the rat bladder enhances bladder contractility. This technique may become a new treatment modality for detrusor underactivity.

Animals↗

Changes in aldehyde dehydrogenase during rat urinary bladder carcinogenesis.

We have reported that normal rat urinary bladder possesses significant amounts of an aldehyde dehydrogenase (class 3 ALDH) expressed during hepatocarcinogenesis, but not detectable in normal liver. Changes in expression of both liver and bladder ALDH during N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced bladder carcinogenesis were studied. The ALDH phenotype was determined at intervals over 42 weeks by histochemical analysis, total ALDH activity assays and gel electrophoresis using propionaldehyde and NAD (P-NAD) which characterizes class 1 and 2 ALDH, or benzaldehyde and NADP (B-NADP) to determine class 3 ALDH. By total activity assays and gel electrophoresis, there was a significant decrease in bladder class 3 ALDH activity during weeks 5-15. Histochemical analysis clearly demonstrates changes in ALDH early in neoplastic development. Intense staining with B-NADP in regions of hyperplasia was first detectable at week 10. Staining in hyperplastic regions was accompanied by a significant decrease in ADLH in neighboring, apparently normal urothelium. As the urothelium became more abnormal, class 3 ALDH activity increased. By week 25, the bladder class 3 ALDH activity of BBN-treated animals was 2 times greater than the control group class 3 ALDH activity. Histochemically, all papillomas and carcinomas examined possessed class 3 ALDH. However, staining was heterogeneous within the lesions. Bladder neoplasm class 3 ALDH specific activity was greater than control group class 3 ALDH activity in 70% of papillomas and carcinomas. These results suggest events may be occurring in bladder similar to those in liver which alter expression of aldehyde dehydrogenase during carcinogenesis.

Aldehyde Dehydrogenase↗

Lewis blood group antigens in urine sediments from patients with urinary bladder carcinoma.

Urine sediments from 20 patients with urinary bladder carcinoma, and from 11 healthy individuals were investigated for their content of Lea and Leb active glycolipids. The investigation was restricted to blood group phenotype Le (a-b+). All individuals exhibited both Lea- and Leb-active glycolipids. In healthy individuals the ratio Lea/Leb was less than 1 in 10 out of 11 cases, whereas in patients with bladder cancer the ratio Lea/Leb was greater than 1 in 11 out of 20 cases. No correlation between the Lea/Leb ratio on the one hand and tumour grade or stage on the other hand could be shown. The results indicate one possible explanation for the loss of ABH antigens in bladder cancer and also demonstrate the potential of detailed biochemical investigations on exfoliated material in urine.

Carcinoma, Transitional Cell↗

[A case of secondary malignant lymphoma of the urinary bladder].

A case of secondary malignant lymphoma of the urinary bladder is presented. Clinical diagnosis was metastatic small cell carcinoma in urinary bladder. Pathological diagnosis after autopsy, however, revealed vesical involvement of malignant lymphoma. The primary focus was considered to be the lung, the biopsy specimen of which was initially diagnosed as small cell carcinoma, because clinical manifestation first occurred in the lung and the metastasis to subcutaneous tissue, bladder and other abdominal organs was found subsequently. In a study of secondary involvement of genitourinary organs as seen in the present case, we reviewed 303 patients who had died of malignant lymphoma at our institute between 1960 and 1985.

Adult↗

Effects of oral administration of manganese on the kidneys and urinary bladder of Sprague-Dawley rats.

The purpose of this study was to investigate the effect of oral administration of manganese acetate on the kidneys and urinary bladder of Sprague-Dawley (SD) rats. Male and female SD rats (150 to 175 g), 6 weeks old, were administered varying doses of manganese acetate for 63 days by oral gavage. At the end of 63 days, 50% of the animals were sacrificed and kidney tissue was isolated and fixed for histopathological studies (study A). The remaining 50% were cross-mated and dosing ceased. Animals were sacrificed after 2 weeks (study B). Male treated animals were noted to have viscous, gritty urine in the urinary bladder, and the high-dose groups had urinary bladder stones (uroliths). Histopathologically, the most striking lesions were observed in the kidneys and prostate glands of male animals. Mild-to-moderate tubulointerstitial nephritis with tubular proteineous and glomerulosclerosis was observed in animals of all treatment groups. Urolithiasis in the urinary bladder was confirmed in 33% to 66% of treated animals. Female animals did not show a significant difference above controls in renal tissues. Results of this study suggest that male rats are more sensitive to the effects of high levels of manganese given orally than female rats and that the genitourinary structures represent target organs of toxicity.

Administration, Oral↗

Effects of acute complete outlet obstruction on the NADPH-diaphorase reactivity in the intramural ganglia of the guinea pig urinary bladder: light and electron microscopic studies.

PURPOSE: The present study aims to examine the effect of complete outlet obstruction on the nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) reactivity in the intramural ganglion cells of the guinea pig urinary bladder. MATERIALS AND METHODS: Adult male guinea pigs were divided into control (normal and sham-operated) and urethral obstructed (12, 24, and 48 hours after complete obstruction) groups. NADPH-d reactivity in the intramural neurons of the urinary bladder was examined by light and electron microscopy. RESULTS: At 12 hours after urethral obstruction, an increase in number of intensely stained NADPH-d intramural neurons was detected. This was sustained till 24 hours whence some of the neurons appeared to undergo degenerative changes. Neuronal degeneration was more drastic at 48 hours. Results of cell counts showed a 32% reduction in number of NADPH-d positive neurons of the urinary bladder at this time point. Electron microscopy showed that all neurons undergoing degeneration displayed NADPH-d reactivity. A large accumulation of NADPH-d reaction product was observed in degenerating neurons whose mitochondria appeared swollen along with dilatation of Golgi saccules. At 48 hours, some neurons displayed total vacuolation and lysis of mitochondria. CONCLUSION: Present results show that acute complete outlet obstruction can lead to degeneration and consequent cell death in the intramural ganglion cells of the guinea pig urinary bladder. The increased NADPH-d reactivity in such neurons suggests that nitric oxide may be involved in neuronal death in the urinary bladder following acute urinary retention.

Animals↗