Effects of uracil calculi on cell growth and apoptosis in the BBN-initiated Wistar rat urinary bladder mucosa

The different potential of initiated and non-initiated urinary bladder mucosa (UBM) to develop neoplasia was quantitatively evaluated in the male Wistar rat. Initiation of carcinogenesis was accomplished with N-butyl-N- (4-hydroxybutyl) -nitrosamine (BBN). Stimuli for cell proliferation and apoptosis were obtained by exposure followed by withdrawal of 3% Uracil in the diet. The proliferation index (PI) was estimated in UBM immunostained for the proliferating nuclear cell antigen (PCNA). The apoptotic index (AI) and the density of papillary/nodular hyperplasia (PNH) were estimated in hematoxilin-eosin stained sections. PNH was the main proliferative response to the mechanical irritation by uracil, irrespective of previous initiation with BBN. Uracil exposure induced higher PI and PNH density in the initiated rats. After uracil withdrawal, there was a significant increase of the AI in both uracil-treated groups, which correlated well to the respective PNH density. However, at the end of the experiment, PNH incidence and density were significantly higher in the BBN-initiated mucosa, which also presented 18% incidence of papillomas and 27% of carcinomas. Therefore, under prolonged uracil calculi trauma, the UBM of BBN-initiated Wistar rats gives rise to epithelial proliferative lesions that progress to neoplasia through acquired resistance to apoptosis. (C) 1999 Wiley-Liss, Inc.

Chemopreventive property of dietary ginger in rat urinary bladder chemical carcinogenesis

The modifying potential of ginger on the development of preneoplasia and tumors in the male Wistar rat urinary bladder was investigated in a 36-week-long initiation-promotion assay for chemical carcinogenesis. Groups G1 to G3 were given 0.05% N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) in drinking water for 5 weeks and a 3% uracil meal for the subsequent 3 weeks. Groups G4 and G5 were treated with 3% uracil only for the same period. After these steps, groups G2, and G3 and G4 were fed for 26 weeks a ginger extract mixed at 0.5 and 1.0% in a basal diet, respectively. Thirty six weeks after the beginning of the experiment all rats were killed. The multiplicity of urothelial lesions (hyperplasia and neoplasia) was significantly lower (P = 0.013) in group G3 than in groups G1 and G2. The results suggest that 1.0% ginger meal exerts a protective effect on the post-initiation stage of rat chemically-induced urothelial carcinogenesis.

Effects of Diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea] on the urinary bladder of male Wistar rats

Diuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea) is a substituted urea herbicide widely used on agricultural crops such as soy, cotton and sugar cane. In a previous long-term study this herbicide exerted carcinogenic activity on the urinary bladder mucosa of male Wistar rats. In general, the genotoxic and mutagenic potentials of Diuron are considered to be negative. The present study aimed to evaluate the mode of action of Diuron on the urinary bladder mucosa of male Wistar rats. Six-week old male Wistar rats were fed pelleted Nuvilab diet mixed with Diuron at 125, 500 and 2500 ppm. As a positive control, 8.3% sodium saccharin (NaS) was fed in the diet. Preceding the sacrifice of the animals at the 20th week, urinary pH was measured and the genotoxic potential of Diuron was evaluated by the comet assay. Histological urothelial lesions in the urinary bladder and in the renal pelvis mucosa, cell proliferation/apoptosis evaluations, and scanning electron microscopy (SEM) of the urinary bladder mucosa were also performed. No DNA changes were found in urothelial or peripheral blood cells, and urinary pH was comparable to controls in all Diuron groups. In the urinary bladder urothelium, the incidence of simple hyperplasia (SH) by light microscopy was significantly increased (7/10; p < 0.005) in the 2500 ppm Diuron group but not at the lower doses. By SEM, three of five animals treated with 2500 ppm Diuron showed urothelial cell necrosis and hyperplasia. In the renal pelvis, the incidence of SH was significantly increased in the Diuron 500 and 2500 ppm and in the NaS 8.3% groups. Cell proliferation was significantly increased in the Diuron 2500 ppm, (p < 0.05) and NaS 8.3% (p < 0.05) groups. The results indicate that a high dietary concentration of Diuron is associated with urothelial necrosis and continuous regenerative cell proliferation that leads to urothelial hyperplasia. (c) 2006 Elsevier B.V.. All rights reserved.

Absence of DNA damage in multiple organs (blood, liver, kidney, thyroid gland and urinary bladder) after acute fluoride exposure in rats

Fluoride has been widely used in dentistry as a caries prophylactic agent. However, there has been some speculation that excess fluoride could cause an impact on genome integrity. In the current study, the potential DNA damage associated with exposure to fluoride was assessed in cells of blood, liver, kidney, thyroid gland and urinary bladder by the single cell gel (comet) assay. Male Wistar rats aging 75 days were distributed into seven groups: Groups 1 (control), 2, 3, 4, 5, 6 and 7 received 0 (deionized water), 10, 20, 40, 60, 80 and 100 mgF/Kg body weight from sodium fluoride (NaF), respectively, by gastrogavage. These groups were killed at 2 h after the administration of the fluoride doses. The level of DNA strand breaks did not increase in all organs evaluated and at all doses of NaF tested, as depicted by the mean tail moment. Taken together, our results suggest that oral exposure to NaF did not result in systemic genotoxic effect in multiple organs related to fluoride toxicity. Since DNA damage is an important step in events leading to carcinogenesis, this study represents a relevant contribution to the correct evaluation of the potential health risk associated with chemical exposure.

Potential effects of the herbicide Diuron on mammary and urinary bladder two-stage carcinogenesis in a female Swiss mouse model

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Mode of Action of Pulegone on the Urinary Bladder of F344 Rats

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Transcriptional Profile of Diuron-Induced Toxicity on the Urinary Bladder of Male Wistar Rats to Inform Mode of Action

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Expression of genes related to apoptosis, cell cycle and signaling pathways are independent of TP53 status in urinary bladder cancer cells

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Estudo da excreção urinária de cálcio, potássio e sódio com o emprego de citrato de potássio na hipercalciúria idiopática na criança

OBJETIVO: Estudar as relações entre a excreção urinária de cálcio, sódio e potássio e a associação sódio/potássio urinários em crianças com hipercalciúria idiopática em dieta habitual, antes e depois da administração de citrato de potássio na dose de 1mEq/kg/dia. MÉTODOS: Foram estudadas prospectivamente 26 crianças: 19 (73%) meninos e sete (27%) meninas com idade entre dois e 13 anos, portadores de hipercalciúria idiopática recém-diagnosticada por dosagem de cálcio em urina de 24 horas >4mg/kg/dia. O citrato de potássio foi administrado na dose de 1mEq/kg/dia. Foram realizadas dosagens séricas e em urina de 24 horas de cálcio (Ca), potássio(K), sódio (Na) e creatinina (Cr), antes e 15 dias depois da administração diária do citrato de potássio. Para comparar os resultados de cálcio/creatinina (Ca/Cr), potássio/creatinina (K/Cr) e sódio/potássio (Na/K) urinários nos dois momentos, aplicou-se o teste não-paramétrico de Wilcoxon. Para a análise das associações entre Ca/Cr e K/Cr e entre Ca/Cr e Na/Cr foi utilizado o coeficiente de correlação de Pearson. Considerou-se significante p<0,05. RESULTADOS: Após o uso de citrato de potássio, ocorreu significativa redução da calciúria e da relação Na/K urinários, bem como elevação na caliúria. Não houve modificação da excreção urinária de sódio. CONCLUSÕES: em dieta habitual, o citrato de potássio eleva a caliúria e diminui a calciúria em criança hipercalciúricas, sendo um eficaz recurso terapêutico.

Intravaginal electrical stimulation: a randomized, double-blind study on the treatment of mixed urinary incontinence

Background the aim of this study was to compare effective and sham intravaginal electrical stimulation (IES) in treating mixed urinary incontinence. Methods. Between January 2001 and February 2002, 40 women were randomly distributed, in a double-blind study, into two groups: group G1 (n = 20), effective IES, and group G2 (n = 20), sham IES, with follow up at one month. Different parameters was studied: 1. clinical questionnaire, 2. body mass index; 3. 60-min pad test; 4. urodynamic study. The protocol of IES consisted of three 20-min sessions per week over a seven-week period. The Dualpex Uro 996 used a frequency of 4 Hz. Results. There was no statistically significant difference in the demographic data of both groups. The number of micturitions per 24 h after treatment was reduced significantly in both groups. Urge incontinence was reduced to 15% in G1 and 31.5% in G2; there was no significant difference between the groups. In the analog wetness and discomfort sensation evaluations were reduced significantly in both groups. The pretreatment urodynamic study showed no statistical difference in urodynamic parameters between the groups. Ten percent of the women presented involuntary detrusor contractions. In the 60-min pad test, there was a significant reduction in both groups. In regards to satisfaction level, after treatment, 80% of G1 patients and 65% of G2 patients were satisfied. There was no statistically significant difference between the groups. Conclusion. Significant improvement was provided by effective and sham electrostimulation, questioning the effectiveness of electrostimulation as a monotherapy.

A comparative analisys of pelvic floor muscle strength in women with stress and urge urinary incontinence

Aims: To assess pelvic floor muscle (PFM) strength in women with stress urinary incontinence (SUI) and urge urinary incontinence (UUI).Materials and Methods: 51 women were prospectively divided into two groups, according to the symptoms as SUI (G1 = 22) or UUI (G2 = 29). Demographic data, such as number of pads/ 24 hours, number of micturations/ 24 hours and nocturia, delay time of urgent void (i.e., the time period for which an urgent void could be voluntarily postponed), number of parity and vaginal deliveries were obtained using a clinical questionnaire. Objective urine loss was evaluated by 60-min. Pad Test, subjective urine stream interruption test (UST) and visual survey of perineal contraction. Objective evaluations of PFM were performed in all patients (vaginal manometry).Results: Median of age, mean number of pads/ 24 hours, nocturia and warning time were significantly higher in UUI comparing to SUI group. During UST, 45.45% in G1 and 3.44%, in G2, were able to interrupt the urine stream (p < 0.001). The 60-min. Pad Test was significantly higher in G2 compared to G1 women (2.7 +/- 2.4 vs 1.5 +/- 1.9 respectively, p = 0.049). Objective evaluation of PFM strength was significantly higher in the SUI than in the UUI patients. No statistical difference was observed regarding other studied parameters.Conclusion: Pelvic floor muscle weakness was significantly higher in women with UUI when compared to SUI.