Management of OAB in those over age 65.

The International Continence Society (ICS) defines overactive bladder (OAB) as an association of symptoms including "urgency, with or without urge incontinence, usually with increased frequency and nocturia". This conditon has been associated with a decrease in quality of life and a higher related risk of overall health condition decrease, and is rising since its prevalence increases with age and the forecast for the world population estimates an increase of those over 65 years old. Aging alone can be considered a major risk factor for developing OAB symptoms that are considered multifactorial and due to body tissue and anatomic changes, lifestyle-associated factors, comorbidities and personal characteristics. The high prevalence of this condition and multiple etiology factors makes of its treatment a challenge-especially in the older population. A major concern over OAB treatment of elderly patients is the risk of cognitive side effects due to the pharmacologic treatment with anticholinergic drugs. First-line treatment for OAB symptoms are the use of pharmacologic therapy with antimuscarinic drugs, which has been proved to be effective in controlling urgency, urge incontinence episodes, incontinence episodes, and nocturia. The impact caused by this condition is significant regarding the economic and human costs associated bringing into attention the need of studying and reviewing this specific population. Conservative Management and Lifestyle Modifications: Behavioral therapy's aims are to reduce urinary frequency and urgency to an accepted level and to increase bladder outlet volume. It consists of actions to teach patients to improve and learn bladder control. Lifestyle modifications are a conjunct of daily activities that can be managed to have the lowest interference on the functioning of the urinary tract. Pharmacologic Therapy: There are various medications with antimuscarinic properties available for the treatment of OAB symptoms. The most commonly used are oxybutinin, tolterodine, solifenacin, darifenacin, fesosterodine and trospium. Second-line Therapy: OAB treatment accounts for some refractory to conventional treatment patients who will require alternative therapies to achieve improvement of symptoms as the use of intradetrusor injection of botulinum A toxin by binding to receptors on the membrane of cholinergic nerves causing temporary chemodenervation and consequent muscle relaxation. Neuromodulation is also an effective therapy that aims to achieve inhibition of detrusor activity by continuous neural stimulation through peripheral nerves as the use of the tibial nerve or central as it is performed by direct spine stimulation on sacral roots through the implantation of an automated generator. In conclusion, evidence from the literature has shown that antimuscarinic treatment of OAB in the elderly population is safe and effective in improving symptoms and patient's quality of life. Managing OAB symptoms in this population is a great challenge. An optimal therapeutic approach to treat should involve medical treatment with drug and behavioral therapy in addition to lifestyle advice.

Antioxidant supplementation decreases the cell death rate in the prostatic stromal tissue of long-term castrated rats.

OBJECTIVE: The purpose of this study was to compare the effects of castration on cell death rate of the adult rat prostates and to evaluate the benefic action of alpha tocopherol supplementation to avoid apoptosis post-orchiectomy. MATERIAL AND METHODS: Thirty male Wistar rats weighing 250-300g were divided into three groups: group I - they were subjected to bilateral orchiectomy and sacrificed eight weeks after the procedure; group II - subjected to bilateral orchiectomy and alpha-tocopherol supplementation for four weeks preceding the procedure; and group III - subjected to bilateral orchiectomy and alpha-tocopherol supplementation for four weeks preceding the procedure and for eight weeks afterwards. At the end of the experiment, the prostatectomy was performed in all rats. The presence of oxidative stress was determined by assaying the blood level of 8-isoprostane and the occurrence of apoptosis was evaluated by identification of active caspase-3 through immunohistochemical analysis. RESULTS: The statistic analysis of active caspase-3 showed that in the long-term castrated group the detection was higher than in groups were the alpha-tocopherol was supplemented (p=0.007). Analysis of 8-isoprostane levels showed higher concentrations of reactive oxygen species in group I compared to other groups (p < 0.05). Groups II and III presented active caspase-3 lower than in group I (p < 0.05). CONCLUSION: Our exploratory analyses demonstrate a method to study the aging process and its influence on oxidative stress of prostatic tissue and cells death rate. Based on our results we can suggest that alpha tocopherol supplementation can decrease the apoptotic process as well as the oxidative stress levels induced by androgen deprivation of the prostate gland.

Antioxidant supplementation decreases the cell death rate in the prostatic stromal tissue of long-term castrated rats

OBJECTIVE: The purpose of this study was to compare the effects of castration on cell death rate of the adult rat prostates and to evaluate the benefic action of alpha tocopherol supplementation to avoid apoptosis post-orchiectomy. MATERIAL AND METHODS: Thirty male Wistar rats weighing 250-300g were divided into three groups: group I - they were subjected to bilateral orchiectomy and sacrificed eight weeks after the procedure; group II - subjected to bilateral orchiectomy and alpha-tocopherol supplementation for four weeks preceding the procedure; and group III - subjected to bilateral orchiectomy and alpha-tocopherol supplementation for four weeks preceding the procedure and for eight weeks afterwards. At the end of the experiment, the prostatectomy was performed in all rats. The presence of oxidative stress was determined by assaying the blood level of 8-isoprostane and the occurrence of apoptosis was evaluated by identification of active caspase-3 through immunohistochemical analysis. RESULTS: The statistic analysis of active caspase-3 showed that in the long-term castrated group the detection was higher than in groups were the alpha-tocopherol was supplemented (p=0.007). Analysis of 8-isoprostane levels showed higher concentrations of reactive oxygen species in group I compared to other groups (p<0.05). Groups II and III presented active caspase-3 lower than in group I (p<0.05). CONCLUSION: Our exploratory analyses demonstrate a method to study the aging process and its influence on oxidative stress of prostatic tissue and cells death rate. Based on our results we can suggest that alpha tocopherol supplementation can decrease the apoptotic process as well as the oxidative stress levels induced by androgen deprivation of the prostate gland.

Impact of castration with or without alpha-tocopherol supplementation on the urethral sphincter of rats.

OBJECTIVE: To analyze the impact of low levels of testosterone induced by orchiectomy and the effect of alpha-tocopherol supplementation on oxidative stress in the urethral sphincter. MATERIALS AND METHODS: Forty male Wistar rats weighing 250-300 g were divided into four groups with 10 each: Sham group; Orchiectomy group: bilateral orchiectomy; Orchiectomy-pre-Tocopherol group: bilateral orchiectomy preceded by alpha-tocopherol supplementation for four weeks; Orchiectomy-full-Tocopherol group: bilateral orchiectomy with alpha-tocopherol supplementation for four weeks preceding the procedure and for eight weeks afterwards. At the protocol end, animals were euthanized and had the sphincter analyzed stereologically focusing on collagen and muscle fibers percentage. Oxidative stress levels were determined using 8-epi-PGF2. RESULTS: The 8-epi-PGF2 levels were statistically higher (p < 0.0003) in the Orchiectomy group compared to others groups while Sham and Orchiectomy-full-Tocopherol groups presented statistically similar values (p = 0.52). Collagen volumetric densities were significantly lower in Sham and Orchiectomy-full-Tocopherol groups (p < 0.022). Sham group presented statistically greater muscle fiber percent. CONCLUSION: Castration caused oxidative stress in the urethral sphincter complex, with increased collagen deposition. Alpha-tocopherol had a protective effect and its supplementation for twelve weeks provided the greatest protection.

Impact of castration with or without alpha-tocopherol supplementation on the urethral sphincter of rats

OBJECTIVE: To analyze the impact of low levels of testosterone induced by orchiectomy and the effect of alpha-tocopherol supplementation on oxidative stress in the urethral sphincter. MATERIALS AND METHODS: Forty male Wistar rats weighing 250-300g were divided into four groups with 10 each: Sham group; Orchiectomy group: bilateral orchiectomy; Orchiectomy-pre-Tocopherol group: bilateral orchiectomy preceded by alpha-tocopherol supplementation for four weeks; Orchiectomy-full-Tocopherol group: bilateral orchiectomy with alpha-tocopherol supplementation for four weeks preceding the procedure and for eight weeks afterwards. At the protocol end, animals were euthanized and had the sphincter analyzed stereologically focusing on collagen and muscle fibers percentage. Oxidative stress levels were determined using 8-epi-PGF2. RESULTS: The 8-epi-PGF2 levels were statistically higher (p < 0.0003) in the Orchiectomy group compared to others groups while Sham and Orchiectomy-full-Tocopherol groups presented statistically similar values (p = 0.52). Collagen volumetric densities were significantly lower in Sham and Orchiectomy-full-Tocopherol groups (p < 0.022). Sham group presented statistically greater muscle fiber percent. CONCLUSION: Castration caused oxidative stress in the urethral sphincter complex, with increased collagen deposition. Alpha-tocopherol had a protective effect and its supplementation for twelve weeks provided the greatest protection.

α-Tocopherol supplementation avoids apoptosis in the anal sphincter.

PURPOSE: To analyze the influence of α-tocopherol supplementation on the levels of oxidative stress and apoptosis rates in the anal sphincter induced by orchiectomy in rats. METHODS: Forty male Wistar rats weighing 250-300 g, were divided into four groups and sacrificed 8 weeks after: I- Control: sham; II- Orchiectomy: bilateral orchiectomy; III- Pre Orchiectomy Tocopherol: α-tocopherol supplementation for 4 weeks preceding bilateral orchiectomy; IV- Orchiectomy Full Tocopherol: α-tocopherol supplementation for 4 weeks before and 8 weeks after bilateral orchiectomy. The anal sphincter was analyzed stereologically to evaluate the density of collagen and the muscle fibers. The oxidative stress and the apoptosis were determined with 8-isprostane and caspase-3, respectively. RESULTS: The collagen fibers concentration was statistically greater in Orchiectomy group than the others. The muscle fibers concentration was higher in Control and Orchiectomy Full Tocopherol than Orchiectomy and Pre Orchiectomy Tocopherol groups. Orchiectomy group showed higher 8-isoprostane concentrations compared to the other groups (p < 0.0003). Pre Orchiectomy Tocopherol and Orchiectomy Full Tocopherol groups presented caspase-3 levels lower than the Orchiectomy group (0.0072). CONCLUSION: Vitamin supplementation with α-tocopherol for 12 weeks had the highest protection against bilateral orchiectomy generation of reactive oxygen species as well as apoptosis in the muscle fibers of the anal sphincter of rats.

Inhibitory activity of α-tocopherol on apoptosis in the rat bladder wall subjected to androgen deprivation.

Alpha-tocopherol (2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-chromon-8-ol) is used in many previous urological studies. Thus to add to this knowledge in this study we studied the potential inhibitory activity on oxidative stress and process apoptosis on bladder wall in male rats subjected to androgen deprivation. A causal relationship between lower testosterone levels and apoptosis, as a component of castration-induced muscle atrophy, has been shown. Male Wistar rats (250-300 g) were used in this experiment, divided into four groups: control (sham operation; n=10); castration (n=10); castration, with alpha-tocopherol supplementation over preceding four weeks (n=10); and castration, with alpha-tocopherol supplementation over preceding four weeks and subsequent eight weeks (n=10). Activated caspase-3 was detected using a previously described technique, with analysis using stereological methodology. Nonparametric methods were used to test statistical significance, taking a significance level of P<0.005. This study was approved by the ethics committee of the university where the project was developed. The serum testosterone concentrations before castration were less than 20 pg/ml. Analysis of 8-isoprostane showed statistical significance (P<0.0003). The volumetric density of caspase-3 showed significant differences between the groups. There was no statistical significance regarding caspase-3 between sham and alpha-tocopherol plus castration or between the groups that received alpha-tocopherol supplementation. The observations showed that there was greater apoptosis in the group with castration alone than in the groups with alpha-tocopherol supplementation. This finding, together with the induced androgen deprivation and higher 8-isoprostane levels, corroborates the hypothesis that alpha-tocopherol supplementation has an important protective effect under conditions of oxidative stress, thereby avoiding the apoptotic process, especially regarding aging.

[Impact of global postural reeducation for treatment of female stress urinary incontinence]. / Impacto da reeducação postural global no tratamento da incontinência urinária de esforço feminina.

OBJECTIVE: To evaluate the effect of global postural reeducation (GPR) on stress urinary incontinence (SUI) and quality of life in SUI female patients METHODS: The study design was a prospective non-randomized clinical trial. Twenty-six patients with symptoms of SUI were selected from the Urogynecology Outpatient Clinics of the State University of Campinas (Unicamp), state of São Paulo, Brazil. Age ranged from 23 to 72 years old (mean 50.8). All women were submitted to anamnesis, physical exam, postural evaluation and urodynamic testing. Patients were treated by the GPR in individual 50 minute sessions weekly for three months and twice a month for the next three months. All patients were re-evaluated at the end of treatment and six months later by means of General Impression of Improvement, Incontinence Impact, General Perception of Health, Functional Evaluation of the Pelvic Floor, Number of Leaking Episodes and Pad Use. RESULTS: At the end of treatment 4 (16%) of the patients were cured, 18 (72%) had improved significantly and 3 (12%) failed. At 6 months, 6 (24%) were cured, 16 (64%) improved and 3 (12%) failed (p<0.001). Quality of Life questionnaires presented significant improvement (p<0.05) in all domains, with emphasis on General Perception of Health, Incontinence Impact and number of leaking episodes. The Functional Evaluation of the Pelvic Floor and Pad Use also presented significant (p<0.001) improvement. CONCLUSION: These results may demonstrate that GPR is an efficient alternative for treatment of stress urinary incontinence.

Impacto da reeducação postural global no tratamento da incontinência urinária de esforço feminina / Impact of global postural reeducation for treatment of female stress urinary incontinence

OBJETIVO: Avaliar os efeitos da reeducação postural global (RPG) nos sintomas de incontinência urinária de esforço (IUE) e a qualidade de vida em um grupo de mulheres incontinentes. MÉTODOS: Ensaio clínico aberto, tipo antes e depois, prospectivo, não randomizado. Foram selecionadas 26 mulheres com queixa clínica e estudo urodinâmico compatível com IUE, do Ambulatório de Uroginecologia do Hospital das Clínicas da UNICAMP. A idade média foi de 50,76 anos (23 a 72 anos). Todas as mulheres foram avaliadas por anamnese, exames clínicos e uroginecológico, avaliação postural. Todas foram submetidas a tratamento com RPG, em sessões individuais de 50 minutos semanais por três meses e quinzenais por mais três meses. As pacientes foram submetidas a posturas de alongamento propostas pela técnica, em que se coloca em tensão as cadeias musculares responsáveis pela postura estática e estrutura do corpo. O trabalho ativo da paciente nas correções, aliado à atuação do fisioterapeuta, levam ao reequilíbrio das tensões musculares e reestruturação do corpo, o que pode favorecer as funções, especificamente as relacionadas ao assoalho pélvico. Ao término do tratamento, e após seis meses, as pacientes foram reavaliadas através do questionário de impressão geral de melhora, dos domínios relacionados à IUE do King's Health Questinnaire: impacto da incontinência, em que se avaliam os prejuízos na qualidade de vida; percepção geral da saúde, qual a classificação que a paciente dá para sua saúde no momento e a presença do sintoma de perda por esforço; avaliação funcional do assoalho pélvico (AFA) e número de trocas de protetores diários. RESULTADOS: No término do tratamento, quatro pacientes (16 por cento) estavam curadas, dezoito (72 por cento) melhoraram significativamente e três (12 por cento) falharam. Após seis meses, seis pacientes (24 por cento) estavam curadas, 16 (64 por cento) melhoraram e três (12 por cento) falharam (p <0,001). Ao avaliarmos a qualidade de vida das pacientes, observamos melhora significativa (p <0,05) em todos os domínios questionados, destacando-se percepção geral da saúde, impacto da incontinência e número de episódios de perda. A avaliação do funcional do assoalho pélvico (AFA) e do teste do absorvente (número de troca/dia) também mostrou melhora significativa (p<0,001) nos diferentes tempos de coleta. CONCLUSÃO: Os resultados mostram que a RPG pode ser uma alternativa para o tratamento da IUE.

OBJECTIVE: To evaluate the effect of global postural reeducation (GPR) on stress urinary incontinence (SUI) and quality of life in SUI female patients METHODS: The study design was a prospective non-randomized clinical trial. Twenty-six patients with symptoms of SUI were selected from the Urogynecology Outpatient Clinics of the State University of Campinas (Unicamp), state of São Paulo, Brazil. Age ranged from 23 to 72 years old (mean 50.8). All women were submitted to anamnesis, physical exam, postural evaluation and urodynamic testing. Patients were treated by the GPR in individual 50 minute sessions weekly for three months and twice a month for the next three months. All patients were re-evaluated at the end of treatment and six months later by means of General Impression of Improvement, Incontinence Impact, General Perception of Health, Functional Evaluation of the Pelvic Floor, Number of Leaking Episodes and Pad Use. RESULTS: At the end of treatment 4 (16 percent) of the patients were cured, 18 (72 percent) had improved significantly and 3 (12 percent) failed. At 6 months, 6 (24 percent) were cured, 16 (64 percent) improved and 3 (12 percent) failed (p<0.001). Quality of Life questionnaires presented significant improvement (p<0.05) in all domains, with emphasis on General Perception of Health, Incontinence Impact and number of leaking episodes. The Functional Evaluation of the Pelvic Floor and Pad Use also presented significant (p<0.001) improvement. CONCLUSION: These results may demonstrate that GPR is an efficient alternative for treatment of stress urinary incontinence.

Influence of oxidative stress and alpha tocopherol supplementation on urothelial cells of the urinary bladder in ovariectomised rats.

The present study was designed to investigate whether vitamin E supplementation would influence the levels of oxidative stress and the damage to urothelial cell DNA in the bladders of castrated rats. A total of 30 rats of the Wistar breed were divided into 3 groups of 10 animals each. Group 1 underwent a sham procedure and was killed after 30 days; group 2 underwent bilateral oophorectomy and was killed after 30 days without receiving vitamin E supplementation and group 3 underwent bilateral oophorectomy and received vitamin E supplementation at a dose of 1,000 IU/kg once a week intra-muscularly for 30 days. Four weeks after the procedure, the rats were anesthetised and their bladders were rapidly removed, frozen and stored at -70 degrees C for Comet assaying, which was carried out on lymphocytes and vesicular urothelium cells. The 8-isoprostane concentration in plasma was also determined to confirm the presence of oxidative stress. The 8-isoprostane levels found were higher in oophorectomised rats that had not received vitamin E supplementation than in the sham group and the oophorectomised group with vitamin replacement. Tail moment analysis on the urothelial cells demonstrated that the oophorectomised group presented DNA damage that was statistically significant in comparison with the other groups. On the basis of the above data, vitamin E decreased the effects of oophorectomy on lipid peroxidation and avoided the DNA damage observed in urothelial cells.

Pelvic floor exercises with biofeedback for stress urinary incontinence.

OBJECTIVE: Prospective study to objectively evaluate the benefits of pelvic floor strengthening exercises associated to biofeedback for the treatment of stress urinary incontinence. MATERIALS AND METHODS: Fourteen patients diagnosed with stress urinary incontinence (SUI) were selected for this study. All patients underwent a pelvic floor training associated to biofeedback for 12 consecutive weeks. Urodynamic tests, pad test and bladder diary were analyzed at the beginning of the study, at the end and after 3 months. The King's Health Questionnaire (KHQ) was applied before and after treatment to assess the impact in the quality of life. RESULTS: There was a significant reduction in the pad weight (from 14.21 g to 1 g), number of urinary leakage episodes (from 8.14 per day to 2.57 per day) and daytime frequency (from 7.93 per day to 5.85 per day). At urodynamics the authors observed a significant increase in Valsalva leak-point pressure (from 103.93 cm H2O to 139.14 cm H2O), cistometric capacity (from 249.29 mL to 336.43 mL, p = 0.0015) and bladder volume at first desire to void (from 145 mL to 215.71 mL). Those differences were kept during the first 3 months of follow up. The KHQ revealed significant differences except in the case of ''general health perception'', which covers health in general and not exclusively urinary incontinence. CONCLUSION: Treatment of SUI with pelvic floor exercises associated to biofeedback caused significant changes in the parameters analyzed, with maintenance of good results 3 months after treatment.

Pelvic floor exercises with biofeedback for stress urinary incontinence

OBJECTIVE: Prospective study to objectively evaluate the benefits of pelvic floor strengthening exercises associated to biofeedback for the treatment of stress urinary incontinence. MATERIALS AND METHODS: Fourteen patients diagnosed with stress urinary incontinence (SUI) were selected for this study. All patients underwent a pelvic floor training associated to biofeedback for 12 consecutive weeks. Urodynamic tests, pad test and bladder diary were analyzed at the beginning of the study, at the end and after 3 months. The King's Health Questionnaire (KHQ) was applied before and after treatment to assess the impact in the quality of life. RESULTS: There was a significant reduction in the pad weight (from 14.21 g to 1 g), number of urinary leakage episodes (from 8.14 per day to 2.57 per day) and daytime frequency (from 7.93 per day to 5.85 per day). At urodynamics the authors observed a significant increase in Valsalva leak-point pressure (from 103.93 cm H2O to 139.14 cm H2O), cistometric capacity (from 249.29 mL to 336.43 mL, p = 0.0015) and bladder volume at first desire to void (from 145 mL to 215.71 mL). Those differences were kept during the first 3 months of follow up. The KHQ revealed significant differences except in the case of "general health perception", which covers health in general and not exclusively urinary incontinence. CONCLUSION: Treatment of SUI with pelvic floor exercises associated to biofeedback caused significant changes in the parameters analyzed, with maintenance of good results 3 months after treatment.

The inhibitory effect of the flavonoid galangin on urinary bladder smooth muscle contractility is mediated in part by modulation of Ca2+ release from intracellular stores.

The present study was designed to examine the effect of the flavonoid galangin on the muscarinic receptor mediating a carbachol-induced contraction and to investigate the effect of the flavonoid on Ca (2+) release from intracellular stores in the urinary bladder of the pig. Galangin (10(-7) -10(-4)M) produced a concentration-dependent inhibition of the contractile responses to electrical field stimulation (EFS) and carbachol (10(-5)M). Galangin (3 x 10(-5)M) reduced muscle contractions evoked by carbachol (10(-5)M) in calcium-containing solution as well as contractions evoked by carbachol and caffeine (2 x 10(-2)M) in Ca(2+)-free solutions significantly. The flavonoid had a stronger effect on the maximal force of the contractions induced by caffeine, compared to contractions induced by carbachol. These results suggest that galangin has an important effect on the intracellular calcium mobilization, which might be attributed predominantly to its influence on ryanodine-receptors.