Influence of alpha lipoic acid supplementation on urinary bladder morphology of diabetic rats / Influencia de la suplementación con ácido alfa lipoico en la morfología de la vejiga urinaria de ratas diabéticas

Diabetes Mellitus (DM) is a condition marked by hyperglycaemia that causes systemic complications, including urinary vesicle dysfunction due to oxidative stress. Further, antioxidants, as well as alpha lipoic acid (ALA), may be a response to this pathological condition. The present study verified the action of ALA as a supplement in ration on glycemia and urinary vesicle structures of rats induced by streptozotocin. The rats were divided into 4 groups: Control (CG), Alpha Lipoic (ALAG), Diabetic control (DCG), and the Diabetic alpha lipoic (DALAG) group. For induction, the diabetic groups were initially induced with streptozotocin (dose 60 mg/kg). Subsequently, group glycemia was evaluated weekly. After 8 weeks, the rats were euthanized and the bladder was collected. The bladders were histologically processed and the slides were stained with Masson's Trichrome for the histomorphometry of epithelial height, connective and muscular tissue and coloration of PicroSirius Red for further analysis of collagen fibers of the bladder. The data of the glycemia demonstrated an inferior median in DALAG compared to DGC (p<0.01). The epithelial height and percentage of the muscle tissue were greater in DALAG compared to the DGC, but not significant. However, GDAL showed improvement in the organization of collagen fibers. In conclusion, bladder the morphology alterations caused by DM were not alleviated by the administration of ALA in 8 weeks of the experiments.

La diabetes mellitus (DM) es una afección marcada por hiperglucemia que causa complicaciones sistémicas, incluida la disfunción de la vejiga urinaria debido al estrés oxidativo. Además, los antioxidantes, así como el ácido alfa lipoico (ALA), pueden ser una respuesta a esta condición patológica. El presente estudio verificó la acción de ALA como suplemento en la ración sobre la glucemia y las estructuras de la vejiga urinaria de ratas inducidas por estreptozotocina. Las ratas se dividieron en 4 grupos: control (CG), alfa lipoico (ALAG), control diabético (DCG) y el grupo diabético alfa lipoico (DALAG). Para la inducción, los grupos diabéticos se aplicó estreptozotocina (dosis 60 mg/kg). Posteriormente, la glucemia grupal se evaluó semanalmente. Después de 8 semanas, las ratas se sacrificaron y se retiró la vejiga urinaria. Las vejigas se procesaron histológicamente y las muestras se tiñeron con tricromo de Masson para la histomorfometría y así evaluar la altura epitelial, el tejido conectivo y muscular. Además se tiñeron cond PicroSirius Red para un análisis posterior de las fibras colágenas de la vejiga urinaria. Los datos de la glucemia demostraron una mediana inferior en DALAG en comparación con DGC (p <0,01). La altura epitelial y el porcentaje de tejido muscular fueron mayores en DALAG en comparación con el DGC, pero no estadísticamente significativos. Sin embargo, GDAL mostró una mejora en la organización de las fibras de colágeno. En conclusión, la morfología de las alteraciones de la vejiga causada por DM no se alivió con la administración de ALA en 8 semanas de estudio.

Effect of a high-fat diet on the rat bladder wall and bioactive action of Brazil nut oil

ABSTRACT High-fat diet-induced obesity is associated with metabolic disorders. The Brazil nut has bioactive substances and has been used to control the damage caused by obesity in several organs. The work intended to show the damage caused by high-fat diet in the bladder wall and if the Brazil nut oil added to the diet could ameliorate or reverse this effect. Sixty-day-old rats were divided into two groups: C (control, n = 30) and HF (high-fat, n = 30) diets. At 90 days, 10 animals of each group were sacrificed. The others were divided into 4 groups: C and HF (animals that maintained their previous diet, n = 10 for each group) and C / Bno and HF / Bno (animals whose control or high-fat diet was supplemented by Brazil nut oil, n = 10 for each group). Sacrifice occurred at 120 days, and the bladders were removed and analyzed. Epithelial height was increased in the HF compared to the C group. In contrast, the C / Bno had a lower epithelial height compared to the others. The percentage of collagen between the detrusor muscle fibers was significantly greater in C / Bno, HF and HF / Bno than in control group. The HF had a larger muscle fiber diameter than the C group, while the C / Bno presented lower values than the HF and HF / Bno groups. HF diets induced bladder wall damage. These changes in the rat's bladder wall were partially reversed by the Bno.

Impact of intravesical hyaluronic acid treatment on bladder inflammation in interstitial cystitis rat model

ABSTRACT Objective: To evaluate the effect of intravesical hyaluronic acid (HA) treatment on inflammatory cells and the severity of inflammation in an interstitial cystitis rat model created with hydrogen chloride (HCL) via immunohistochemical studies and myeloperoxidase activity for the first time in the literature. Materials and Methods: A total of 30 adult female white Rattus Norvegicus rats were divided into 3 groups as the HCL group, hyaluronic acid treatment (HCL-HA) group and control group. Chemical cystitis was created by administering HCL(400 microL,10 mM) except control group. A single dose of intravesical HA(0.5 mL,0.8 mg/mL) was administered to the treatment group. The bladder tissues of all subjects were immunohistochemically stained. The cell surface markers were used to evaluate inflammatory cell infiltration. Mast cell activation and IL-6 was evaluated to assess the inflammation and severity of inflammation, respectively. Myeloperoxidase activity was measured as it shows neutrophil density. Statistical significance was accepted as P<0.05. Results: It was observed that there was rich monocyte, T lymphocyte, B lymphocyte, and Natural Killer cells infiltration and high IL-6 levels in the bladder tissue after the intravesical hydrogen chloride instillation, especially in the stroma layer(p<0.005). In the HCL-HA group, severity of inflammation had statistically significantly regressed to the levels of the control group(p<0.005). An increase was observed in the bladder myeloperoxidase activity of the HCL group compared to the other two groups(p<0.05). Conclusions: Single dose intravesical hyluronic acid instillation reduces inflammatory cell infiltration and the severity of bladder inflammation in the rat model of bladder pain syndrome/interstitial cystitis.

Effects of Copaiba oil in the healing process of urinary bladder in rats

ABSTRACT Introduction The appropriate closure of the urinary bladder is important to many urologic procedures to avoid the formation of fistulas and strictures by excessive fibrosis. This paper presents the alterations in the bladder healing process of rats after the topical use of Copaiba oil (Copaifera reticulata). Material and Methods Ten male Wistar rats were used and randomly divided into two groups: Control group (CG): injected 1ml/kg of saline solution on the suture line; and Copaiba group (CpG): 0.63ml/kg of copaiba oil applied to the suture line. Euthanasia was performed on the seventh day after surgery. The criteria observed were adherences formation, histopathological modifications and stereology for collagen. Results Both groups showed adhesions to the bladder, with no statistically significant difference (p=0.1481). The microscopic evaluation revealed a trend to more severe acute inflammation process on the CpG, but there was statistical difference only in the giant cells reaction (p=0.0472) and vascular proliferation (p=0.0472). The stereology showed no difference. Conclusion The copaiba oil modified the healing process, improving the quantity of giant cells and vascular proliferation, but not interfered in the collagen physiology.

Intradetrusor onabotulinumtoxinA injections are significantly more efficacious than oral oxybutynin for treatment of neurogenic detrusor overactivity: results of a randomized, controlled, 24-week trial / Injeções intradetrusoras de onabotulinumtoxinA são significativamente mais eficazes que oxibutinina oral para tratamento da hiperatividade detrusora neurogênica: resultados de estudo randomizado e controlado de 24 semanas

ABSTRACT Objective To prospectively compare the results of intradetrusor onabotulinumtoxinA injections and oral oxybutynin for urinary continence, urodynamic parameters and quality of life in patients with neurogenic detrusor overactivity due to spinal cord injury. Methods Adult patients under intermittent catheterization were randomized 1:1 to receive one injection of onabotulinumtoxinA 300U or oxybutynin 5mg, per oris, three times/day. Primary study endpoint was change in urinary incontinence episodes/24 hours and secondary study endpoints were maximum cystometric capacity, maximum detrusor pressure, bladder compliance and quality of life before randomization and at week 24. Results Sixty-eight patients participated in the trial. Significant improvements in urinary incontinence per 24 hours, all investigated urodynamic parameters and quality of life were observed in both groups. Compared with oral oxybutynin, onabotulinumtoxinA was significantly more efficacious for all parameters investigated. Non-response to treatment was higher for oral oxybutynin (23.5%) than onabotulinumtoxinA (11.8%). Dry mouth was the most common adverse in patients with oral oxybutynin (72%) and transient macroscopic hematuria in patients with onabotulinumtoxinA (28%). Only one patient with oral oxybutynin dropped out the study because of adverse effects. Conclusion The comparison of the two study drugs showed that onabotulinumtoxinA was significantly more efficacious than oral oxybutynin with regard to continence, urodynamic parameters and quality of life. Clinicaltrials.gov: NCT:01477736.

RESUMO Objetivo Comparar prospectivamente os resultados de injeções intradetrusoras de onabotulinumtoxinA e oxibutinina oral em pacientes com hiperatividade neurogênica do detrusor devido à lesão da medula espinhal, para avaliar a continência urinária, os parâmetros urodinâmicos e a qualidade de vida. Métodos Pacientes adultos em cateterismo intermitente foram randomizados 1:1 para tratamento com uma injeção de onabotulinumtoxinA 300U ou oxibutinina 5mg via oral, três vezes por dia. O desfecho primário foi alteração nos episódios de incontinência urinária em 24 horas, e os secundários foram capacidade cistométrica máxima, pressão máxima do detrusor, complacência vesical e qualidade de vida antes da randomização e na 24ª semana. Resultados Participaram do estudo 68 pacientes. Observou-se melhora significativa na incontinência urinária por 24 horas em todos os parâmetros urodinâmicos investigados e na qualidade de vida em ambos os grupos. Em comparação com a oxibutinina oral, a onabotulinumtoxinA foi significativamente mais eficaz para todos os parâmetros investigados. A falha no tratamento foi maior para oxibutinina oral (23,5%) em comparação com onabotulinumtoxinA (11,8%). A boca seca foi o evento adverso mais comum em pacientes tratados com oxibutinina oral (72%), e a hematúria macroscópica transitória naqueles tratados com onabotulinumtoxinA (28%). Apenas um paciente tratado com oxibutinina oral interrompeu o estudo por conta dos efeitos adversos. Conclusão A comparação dos dois fármacos do estudo mostrou que onabotulinumtoxinA foi significativamente mais eficaz que oxibutinina oral em relação a continência, parâmetros urodinâmicos e qualidade de vida. Clinicaltrials.gov: NCT:01477736.

Effects of nitric oxide inhibitors in mice with bladder outlet obstruction

ABSTRACT Purpose To investigate the lower urinary tract changes in mice treated with L-NAME, a non-selective competitive inhibitor of nitric oxide synthase (NOS), or aminoguanidine, a competitive inhibitor of inducible nitric oxide synthase (iNOS), after 5 weeks of partial bladder outlet obstruction (BOO), in order to evaluate the role of constitutive and non-constitutive NOS in the pathogenesis of this experimental condition. Materials and Methods C57BL6 male mice were partially obstructed and randomly allocated into 6 groups: Sham, Sham + L-NAME, Sham + aminoguanidine, BOO, BOO + L-NAME and BOO + aminoguanidine. After 5 weeks, bladder weight was obtained and cystometry and tissue bath contractile studies were performed. Results BOO animals showed increase of non-voiding contractions (NVC) and bladder capacity, and also less contractile response to Carbachol and Electric Field Stimulation. Inhibition of NOS isoforms improved bladder capacity and compliance in BOO animals. L-NAME caused more NVC, prevented bladder weight gain and leaded to augmented contractile responses at muscarinic and electric stimulation. Aminoguanidine diminished NVC, but did not avoid bladder weight gain in BOO animals and did not improve contractile responses. Conclusion It can be hypothesized that chronic inhibition of three NOS isoforms in BOO animals leaded to worsening of bladder function, while selective inhibition of iNOS did not improve responses, what suggests that, in BOO animals, alterations are related to constitutive NOS.

Extracellular adenosine 5'-triphosphate concentrations changes in rat spinal cord associated with the activation of urinary bladder afferents. A microdialysis study. / Variação da concentração extracelular de 5'-trifosfato de adenosina na medula espinal de rata associadas a fibras aferentes vesicais. Um estudo com microdiálise

ABSTRACT Objective To determine adenosine 5’-triphosphate levels in the interstice of spinal cord L6-S1 segment, under basal conditions or during mechanical and chemical activation of urinary bladder afferents. Methods A microdialysis probe was transversally implanted in the dorsal half of spinal cord L6-S1 segment in female rats. Microdialysate was collected at 15 minutes intervals during 135 minutes, in anesthetized animals. Adenosine 5’-triphosphate concentrations were determined with a bioluminescent assay. In one group of animals (n=7) microdialysate samples were obtained with an empty bladder during a 10-minutes bladder distension to 20 or 40cmH2O with either saline, saline with acetic acid or saline with capsaicin. In another group of animals (n=6) bladder distention was performed and the microdialysis solution contained the ectonucleotidase inhibitor ARL 67156. Results Basal extracellular adenosine triphosphate levels were 110.9±35.34fmol/15 minutes, (mean±SEM, n=13), and bladder distention was associated with a significant increase in adenosine 5’-triphosphate levels which was not observed after bladder distention with saline solution containing capsaicin (10µM). Microdialysis with solution containing ARL 67156 (1mM) was associated with significantly higher extracellular adenosine 5’-triphosphate levels and no further increase in adenosine 5’-triphosphate was observed during bladder distension. Conclusion Adenosine 5’-triphosphate was present in the interstice of L6-S1 spinal cord segments, was degraded by ectonucleotidase, and its concentration increased following the activation of bladder mechanosensitive but not of the chemosensitive afferents fibers. Adenosine 5’-triphosphate may originate either from the central endings of bladder mechanosensitive primary afferent neurons, or most likely from intrinsic spinal neurons, or glial cells and its release appears to be modulated by capsaicin activated bladder primary afferent or by adenosine 5’-triphosphate itself.

RESUMO Objetivo Determinar as concentrações extracelulares do 5’-trifosfato de adenosina no interstício dos segmentos medulares L6-S1, em condições basais ou durante a ativação mecânica e química das fibras aferentes vesicais. Métodos Um cateter de microdiálise foi implantado no sentido transversal na parte dorsal da medula espinal, entre os segmentos L6-S1 de ratas. O microdialisado foi coletado em intervalos de 15 minutos, durante 135 minutos, com os animais anestesiados. A concentração de 5’-trifosfato de adenosina nas amostras foi determinada mediante ensaio de bioluminescência. Em um grupo de animais (n=7), as amostras de microdialisado foram obtidas com a bexiga vazia, com distensão da bexiga para volume de 20 ou 40cmH2O, com solução salina, solução salina com ácido acético, ou solução salina com capsaicina. Em outro grupo (n=6), foi realizada com a bexiga distendida, e a solução para microdiálise continha o inibidor de ectonucleotidase ARL 67156. Resultados Os níveis extracelulares de trifosfato de adenosina no início do estudo foram 110,9±35,36fmol/15 minutos (média±EPM, n=13), e a distensão da bexiga causou um aumento nos níveis de 5’-trifosfato de adenosina, o que não foi observado após a distensão da bexiga com solução salina contendo capsaicina (10µM). A microdiálise com solução contendo ARL 67156 (1mM) foi associada com significante aumento dos níveis de trifosfato de adenosina extracelular, e nenhum aumento do trifosfato de adenosina foi observado durante a distensão da bexiga. Conclusão O 5’-trifosfato de adenosina está presente no interstício do segmento L6-S1 da medula espinal, é degradado por ectonucleotidases, e sua concentração aumentou com a ativação das fibras aferentes mecanossensíveis da bexiga, mas não das quimiossensíveis. O 5’-trifosfato de adenosina pode ter sido liberado das terminações centrais dos neurônios aferentes primários mecanossensíveis ou, mais provavelmente, de neurônios espinais intrínsecos, ou ainda de células gliais. Sua liberação parece ser modulada por fibras aferentes primárias da bexiga ativadas pela capsaicina ou pelo próprio 5’-trifosfato de adenosina.

Effect of S-methyl-l-thiocitrulline dihydrochloride on rat micturition reflex

ABSTRACT Objective: To evaluate the effect of neuronal nitric oxide synthase on the striated urethral sphincter and the urinary bladder. Materials and Methods: A coaxial catheter was implanted in the proximal urethra and another one in the bladder of female rats, which were anesthetized with subcutaneous injection of urethane. The urethral pressure with saline continuous infusion and bladder isovolumetric pressure were simultaneously recorded. Two groups of rats were formed. In group I, an intrathecal catheter was implanted on the day of the experiment at the L6-S1 level of the spinal cord; in group II, an intracerebroventricular cannula was placed 5-6 days before the experiment. Results: It was verified that the group treated with S-methyl-L-thio-citrulline, via intrathecal pathway, showed complete or partial inhibition of the urethral sphincter relaxation and total inhibition of the micturition reflexes. The urethral sphincter and the detrusor functions were recovered after L-Arginine administration. When S-methyl-L-thio-citrulline was administered via intracerebroventricular injection, there was a significant increase of urethral sphincter tonus while preserving the sphincter relaxation and the detrusor contractions, at similar levels as before the use of the drugs. Nevertheless there was normalization of the urethral tonus when L-Arginine was applied. Conclusions: The results indicate that, in female rats anaesthetized with urethane, the nNOS inhibitor administrated through the intrathecal route inhibits urethral sphincter relaxation, while intracerebroventricular injection increases the sphincter tonus, without changing bladder function. These changes were reverted by L-Arginine administration. These findings suggest that the urethral sphincter and detrusor muscle function is modulated by nitric oxide.

Bladder carcinogenesis in rats subjected to ureterosigmoidostomy and treated with L-lysine / Carcinogênese de bexiga em ratas submetidas à ureterossigmoidostomia tratadas com L-lisina

ABSTRACT Objective: to evaluate the effect of L-lysine in the bladder and intestinal epithelia in rats submitted to vesicosigmoidostomy. Methods: we divided forty Wistar rats into four groups: group I - control group (Sham); group II - submitted to vesicosigmoidostomy and treated with L-lysine 150mg/kg; group III - submitted only to vesicosigmoidostomy; and group IV - received L-lysine 150mg/kg. After eight weeks the animals were sacrificed. Results: in the bladders of all operated animals we observed simple, papillary and nodular hyperplasia of transitional cells, transitional cell papillomas and squamous metaplasia. As for the occurrence of aberrant crypt foci in the colons of operated animals, we did not observe statistically significant differences in any of the distal, proximal and medium fragments, or in all fragments together (p=1.0000). Conclusion: Although statistically there was no promotion of carcinogenesis in the epithelia of rats treated with L-lysine in the observed time, it was clear the histogenesis of bladder carcinogenesis in its initial phase in all operated rats, this being probably associated with chronic infection and tiny bladder stones.

RESUMO Objetivo: o objetivo deste trabalho é avaliar o efeito da L-lisina nos epitélios vesical e intestinal de ratas submetidas à vesicossigmoidostomia. Métodos: quarenta ratas Wistar, foram divididas em quatro grupos: grupo I- grupo controle (Sham); grupo II- submetido à vesicossigmoidostomia e tratado com L-lisina 150mg/kg; grupo III- submetido apenas à vesicossigmoidostomia; e grupo IV- recebeu L-lisina 150mg/kg. Após oito semanas os animais foram sacrificados. Resultados: na bexiga de todos os animais operados observou-se hiperplasia simples, papilar e nodular de células transicionais, papiloma de células transicionais e metaplasia escamosa. Quanto à ocorrência de focos de criptas aberrantes nos colos dos animais operados, não foi evidenciado diferença estatística significante em nenhum dos fragmentos distal, proximal e médio, e todos juntos (P=1,0000). Conclusão: apesar de, estatisticamente, não ter havido promoção de carcinogênese nos epitélios dos ratos tratados com L-lisina, no tempo observado, é nítida a histogênese da carcinogênese de bexiga em sua fase inicial, no epitélio vesical, em todos os ratos operados, estando esta provavelmente associada à infecção crônica e aos diminutos cálculos vesicais.

Efficacy of botulinum toxin type A 100 units versus 200 units for treatment of refractory idiopathic overactive bladder

Objective: To evaluate the efficacy and safety of a single intra detrusor injection of BoNTA comparing two different doses (100 U or 200 U) in patients with idiopathic overactive bladder. Materials and Methods: A randomized prospective study evaluated the efficacy of BoNTA in management of refractory idiopathic overactive bladder and included 80 patients. All patients were assessed initially by taking a history, a physical examination, overactive bladder symptom score, urine analysis, routine laboratory investigations, KUB and pelviabdominal. OABSS was adjusted on all patients postoperative at 1,3,6,9 months also Urodynamic was done for all patients preoperative and postoperative at 3, 6, 9 months. Results: The mean age was 30.22±8.37 and 31.35±7.61 in group I and II respectively. There was no statistically difference between both groups in all parameters all over the study except at 9 months after treatment. Hematuria was observed 6 and 9 patients in group I and II respectively. Dysuria was observed in 6 and 15 patients in group I and II respectively. UTI was detected in 3 and 7 patients in group I and II respectively. Conclusion: A single-injection procedure of 100 U or 200 U BoNTA is an effective and safe treatment for patients with IOAB who failed anticholinergic regimens. OABSS and QoL were improved for 6 months; 100 U injections seemed to have comparable results with 200 U. There was a significant difference at month 9 towards 200 U with more incidences of adverse events.

Functional and biochemical characteristics of urinary bladder muscarinic receptors in long-term alloxan diabetic rats / Características funcionais e bioquímicas dos receptores muscarínicos da bexiga de ratos com diabetes crônico induzido por aloxana

Objective To re-examine the function of the urinary bladder in vivoas well as to determine the functional and biochemical characteristics of bladder muscarinic receptors in long-term alloxan-induced diabetes rats.Methods Two-month-old male Wistar rats were injected with alloxan and the animals showing blood glucose levels >300mg/dL together with age-paired untreated animals were kept for 11 months. Body weight, bladder weight, blood glucose, and urinary volume over a period of 24 hours were determined in both groups of animals. A voiding cystometry in conscious control and diabetic rats was performed to determine maximal micturition pressure, micturition contraction interval and duration as well as voided and post-voiding residual volume. In addition, concentration-response curves for bethanechol in isolated bladder strips, as well as [3H]-N methyl-scopolamine binding site characteristics in bladder homogenates were determined.Results Mean bladder weight was 162.5±21.2mg versus 290±37.9mg in control and treated animals, respectively (p<0.05). Micturition contraction amplitude (34.6±4.7mmHg versus 49.6±2.5mmHg), duration (14.5±1.7 seconds versus 23.33±4.6 seconds) and interval (87.5±17.02 seconds versus 281.11±20.24 seconds) were significantly greater in alloxan diabetic rats. Voided urine volume per micturition contraction was also significantly higher in diabetic animals. However the post-voiding residual volume was not statistically different. Bethanechol potency (EC50 3µM versus 5µM) and maximal effect (31.2±5.9g/g versus 36.1±6.8g/g) in isolated bladder strips as well as number (169±4fmol/mg versus 176±3fmol/mg protein) and affinity (0.69±0.1nM versus 0.57±0.1nM) of bladder muscarinic receptors were also not statistically different.Conclusion Bladder function in vivo is altered in chronic alloxan-induced diabetes rats without changes in functional and biochemical characteristics of bladder muscarinic receptors.

Objetivo Reestudar o funcionamento da bexiga in vivo e determinar as características funcionais e bioquímicas dos receptores muscarínicos vesicais de ratos com diabetes crônico induzido por aloxana.Métodos Ratos Wistar de dois meses de idade receberam injeção de aloxana, e os animais que apresentaram glicemia >300mg/dL foram mantidos por 11 meses junto de outros não tratados e pareados por idade. Nos dois grupos de animais, peso corpóreo, peso da bexiga, glicemia e volume urinário de 24 horas foram medidos. Em ambos os grupos, realizou-se a cistometria miccional em animais não anestesiados. Foram determinados os seguintes parâmetros: pressão máxima de micção, intervalo e contração de micção, bem como o volume de esvaziamento e o volume residual pós-miccional. Além disso, foram determinadas as curvas de concentração-resposta a betanecol em preparações isoladas de bexiga e também as características dos sítios de ligação da [3H]-N-metil-escopolamina em homogenatos de bexiga.Resultados O peso médio da bexiga foi de 162,5±21,2mg versus290±37,9mg nos animais controles e tratados, respectivamente (p<0,05). A amplitude de contração (34,6±4,7mmHg versus 49,6±2,5mmHg), a duração (14,5±1,7 segundos versus 23,33±4,6 segundos) e o intervalo (87,5±17,02 segundos versus 281,11±20,24 segundos) de micção foram significantemente maiores nos ratos tratados com aloxana. O volume de urina eliminada durante a contração miccional também foi maior nos animais diabéticos. Contudo, o volume residual pós-miccional não foi estatisticamente diferente. Não foram observadas diferenças na resposta ao betanecol (EC50 3µM versus 5µM) e no seu efeito máximo (31,2±5,9g/g versus 36,1±6,8g/g) em preparações isoladas de bexiga, bem como no número total (169±43fmol/mgversus 176±3fmol/mg) e na afinidade (0,69±0,1nMversus 0,57±0,1nM) dos receptores muscarínicos da bexiga.Conclusão O funcionamento da bexiga in vivo está alterado no diabetes crônico induzido por aloxana, porém sem alterações funcionais e bioquímicas nos receptores muscarínicos da bexiga.

Effects of Moderate Alcohol Intake in the Bladder of the Otsuka Long Evans Tokushima Fatty Diabetic Rats

Diabetes is related with a number of cystopathic complications. However, there have been no studies about the influence of alcohol consumption in the bladder of type 2 diabetes. Thus, we investigated the effect of moderate alcohol intake in the bladder of the Otsuka Long Evans Tokushima Fatty (OLETF) diabetic rat. The non-diabetic Long-Evans Tokushima Otsuka (LETO, n=14) and the OLETF control group (n=14) were fed an isocaloric diet; the LETO (n=14) and the OLETF ethanol group (n=14) were fed 36% ethanol 7 g/kg/day. After ten weeks, muscarinic receptors, RhoGEFs, myogenic change, and the level of oxidative stress were evaluated. Moderate alcohol intake significantly decreased excessive muscarinic receptor and Rho kinase expressions in the OLETF rats compared with the LETO rats. In addition, iNOS and collagen expression were not changed in the OLETF rats in spite of alcohol consumption. Superoxide dismutase levels, which is involved in antioxidant defense, in the LETO rats were significantly decreased after alcohol consumption, however those in the OLETF rats were similar. Moderate alcohol consumption reduces the oxidative stress, and may prevent molecular and pathologic changes of the bladder of rats with type 2 diabetes.

Penicillin G-induced hemorrhagic cystitis

No abstract available.

Analysis of the histology of the scar bladder and biochemical parameters of rats with a solitary kidney undergoing immunosuppression with tacrolimus

PURPOSE: To evaluate bladder histology in healing and biochemical analysis of rats with single kidney in ischemia/reperfusion, treated with tacrolimus. METHODS: Fifty rats randomized into five groups. Three rats died in surgery, 47 rats divided in groups: Control (non-operated, n=10), Sham (operated without drugs, n=8), T1 (operated + tacrolimus 1mg/kg, n=10), T2 (operated + tacrolimus 0.1 mg/kg, n=10), T3 (operated + tacrolimus 10mg/kg, n=9). The surgery was: laparotomy, right nephrectomy, left kidney ischemia/reperfusion, cystotomy followed by bladder suture. After that, rats were submited to gavage daily (Control and Sham with saline solution. T1, T2, T3 with tacrolimus in doses already mentioned). On the 14th day, after death induction, cystectomy was performed and bladder was histologicaly analysed. The serum urea, creatinine and tacrolimus were analysed too. RESULTS: There was difference in serum tacrolimus in T3 compared to the other groups (p<0.05). There was higher doses of creatinine in T3 group and higher urea in groups with tacrolimus. There were significant differences among all histologic variables comparing groups with and without tacrolimus (p<0.05). CONCLUSION: Tacrolimus associated with ischemia/reperfusion is nephrotoxic, suppresses inflammation and seems to delay the healing bladder. .

Effects of prepubertal corticosterone treatment on urinary bladder

PURPOSE: The aim of this work was to analyze the bladder wall modifications after a chronic treatment with high doses of corticosterone in prepubertal rats. METHODS: This study included 26 male rats assigned into four groups: T30 was treated with corticosterone until 29 days of age and killed at day 30, while T65 group received the same treatment but was killed at day 65. Each group had its own control group (C30 and C65). For treated animals, daily intraperitoneal injections of corticosterone (20 mg/Kg) were administered between 7th and 29th day of life. Bladders were removed and collagen, smooth muscle, elastic fibers system, vascular density and epithelium were analyzed by morphometrical methods, immunofluorescence, and biochemistry. RESULTS: Vascular density in lamina propria was reduced by 40% (p<0.05) in group T65. Collagen organization was altered in T30 and T65, although total collagen concentration was unchanged. The T65 group had an increase in elastic system fibers. There was no difference in epithelial height and cell density between the groups. Concerning the smooth muscle fibers density we observed a 19% increase (p<0.05) in the T65 group. CONCLUSION: Prepubertal administration of corticosterone induces structural modifications in the bladder of rats in a medium term analysis. .

Expression of alpha1 Receptor and Nitric Oxide Synthase in Oophorectomized and Estrogen-Supplemented Rat Bladder and Urethra

PURPOSE: To investigate the effects of estrogen on the expression of the alpha1 receptor and nitric oxide synthase (NOS) in rat urethra and bladder after oophorectomy. MATERIALS AND METHODS: Forty-five mature female Sprague-Dawley rats (aged 10-11 weeks, 235-250 g) were randomly assigned to one of three groups: control group, oophorectomy group (Opx), or oophorectomy and estradiol replacement group (Opx+ Est). The degree of expression of alpha1 receptor (alpha1A and D) and NOS (neuronal NOS [nNOS] and endothelial NOS [eNOS]) in bladder and urethral tissues was investigated by using immunohistochemical staining and Western blotting. RESULTS: In the bladder, the expression rates of alpha1 receptor (alpha1A and alpha1D) increased in the Opx group but decreased in the Opx+Est group. These changes were not statistically significant. The alpha1A and alpha1D receptor of the urethra decreased in the Opx group but increased in the Opx+Est group. These changes were not statistically significant. In the bladder and urethra, the expression rates of nNOS and eNOS significantly increased in the Opx group but decreased in the Opx+Est group (p<0.05). CONCLUSIONS: These data suggest that estrogen depletion increases NOS and alpha1 receptor expression in the rat bladder. However, these changes could be restored by estrogen replacement therapy.

Penicillin G-induced hemorrhagic cystitis: a case and review of the literature

No abstract available.

Effect of caffeine on bladder function in patients with overactive bladder symptoms

To evaluate the effect of caffeine at the dose of 4.5 mg/kg on bladder function in overactive bladder [OAB] adults. Nine women and three men aged 21-40 years with OAB symptoms were included. Each subject drank 8 ml/kg of water with and without caffeine at two separate sessions. Cystometry and uroflowmetry were performed 30 minutes after each drink. The effects of caffeine on urodynamic parameters were compared. After caffeine ingestion, the mean volume at bladder filling phase decreased at first desire to void and normal desire to void [P<0.05], compared to the mean volume after taking water [control] drink. The mean volume at strong desire to void, urgency and maximum cystometric capacity also tended to decrease. No change in the detrusor pressure at filling phase was found. At voiding phase, the maximal flow rate, average flow rate and voided volume were increased [P<0.05]. The urine flow time and time to maximal flow rate were not changed. Caffeine at 4.5 mg/kg caused diuresis and decreased the threshold of sensation at filling phase, with an increase in flow rate and voided volume. So, caffeine can promote early urgency and frequency of urination. Individuals with lower urinary tract symptom should avoid or be cautious in consuming caffeine containing foodstuffs

Effect of hydrogen peroxide on rabbit urinary bladder citrate synthase activity in the presence and absence of a grape suspension

PURPOSE: The etiology of obstructive bladder dysfunction includes free radical damage to mitochondria. Feeding rabbits a standardized grape suspension protects the ability of the bladder to contract and empty in part by preventing mitochondrial damage, thus maintaining smooth muscle and mucosal metabolism. The objective of the current study is to determine the direct effect of this grape suspension on the response of mitochondria to the oxidative effects of hydrogen peroxide. MATERIALS AND METHODS: Six male rabbits were anesthetized with sodium pentobarbital and the bladders excised. Four full thickness strips were obtained for contractile studies and the balance separated into smooth muscle and mucosa compartments by blunt dissection. The effect of hydrogen peroxide on the contractile response to field stimulation was quantitated. Each tissue was homogenized and the effects of increasing concentrations of hydrogen peroxide in the presence and absence of grape suspension on citrate synthase activity was determined. RESULTS: Citrate synthase activity was significantly higher in the mucosa than in the muscle. The grape suspension had no effect on control citrate synthase activity. However, the grape suspension provided significant protection of both smooth muscle and mucosal citrate synthase activity. CONCLUSIONS: These studies support the conclusion that the grape suspension provides direct protection of mitochondrial function.