Overactive bladder-18 years - Part II

Traditionally, the treatment of overactive bladder syndrome has been based on the use of oral medications with the purpose of reestablishing the detrusor stability. The recent better understanding of the urothelial physiology fostered conceptual changes, and the oral anticholinergics - pillars of the overactive bladder pharmacotherapy - started to be not only recognized for their properties of inhibiting the detrusor contractile activity, but also their action on the bladder afference, and therefore, on the reduction of the symptoms that constitute the syndrome. Beta-adrenergic agonists, which were recently added to the list of drugs for the treatment of overactive bladder, still wait for a definitive positioning - as either a second-line therapy or an adjuvant to oral anticholinergics. Conservative treatment failure, whether due to unsatisfactory results or the presence of adverse side effects, define it as refractory overactive bladder. In this context, the intravesical injection of botulinum toxin type A emerged as an effective option for the existing gap between the primary measures and more complex procedures such as bladder augmentation. Sacral neuromodulation, described three decades ago, had its indication reinforced in this overactive bladder era. Likewise, the electric stimulation of the tibial nerve is now a minimally invasive alternative to treat those with refractory overactive bladder. The results of the systematic literature review on the oral pharmacological treatment and the treatment of refractory overactive bladder gave rise to this second part of the review article Overactive Bladder - 18 years, prepared during the 1st Latin-American Consultation on Overactive Bladder.Univ Fed Sao Paulo, EPM, Sao Paulo, SP, BrazilUniv Sao Paulo, Dept Urol, BR-05508 Sao Paulo, SP, BrazilFac Med ABC, Dept Urol, Sao Paulo, SP, BrazilUniv Los Andes, Dept Urol, Bogota, ColombiaEscuela Med Mil, Dept Urol, Mexico City, DF, MexicoHosp Clin Jose San Martin, Catedra Urol, Buenos Aires, DF, ArgentinaMae de Deus Ctr Hosp, Dept Urol, Porto Alegre, RS, BrazilUniv Fed Ciencias Saude Porto Alegre, Porto Alegre, RS, BrazilAC Camargo Hosp, Dept Urol, Sao Paulo, SP, BrazilHosp Clinico Fuerza Area Chile, Santiago, ChileInst Mexicano Seguro Social, Mexico City, DF, MexicoHosp Souza Aguiar, Dept Urol, Rio De Janeiro, RJ, BrazilComplejo Med Policial Churruca Visca, Serv Urol, Buenos Aires, DF, ArgentinaCtr Policlin Valencia Vina, Valencia, VenezuelaHosp Pablo Tobon Uribe, Medellin, ColombiaClin Indisa, Serv Urol, Providencia, ChileCtr Reabilitacao & Readaptacao Dr Henriqe Santill, Goiania, Go, BrazilHosp Univ Caracas, Serv Urol, Caracas, VenezuelaUniv Fed Ceara, Div Urol, Fortaleza, Ceara, BrazilUniv Fed Sao Paulo, EPM, Sao Paulo, SP, BrazilWeb of Scienc

Overactive bladder-18 years - Part I

Overactive bladder syndrome is one of the lower urinary tract dysfunctions with the highest number of scientific publications over the past two decades. This shows the growing interest in better understanding this syndrome, which gathers symptoms of urinary urgency and increased daytime and nighttime voiding frequency, with or without urinary incontinence and results in a negative impact on the quality of life of approximately one out of six individuals - including both genders and almost all age groups. The possibility of establishing the diagnosis just from clinical data made patients' access to specialized care easier. Physiotherapy resources have been incorporated into the urological daily practice. A number of more selective antimuscarinic drugs with consequent lower adverse event rates were released. Recently, a new class of oral drugs, beta-adrenergic agonists has become part of the armamentarium for Overactive Bladder. Botulinum toxin injections in the bladder and sacral neuromodulation are routine modalities of treatment for refractory cases. During the 1st Latin-American Consultation on Overactive Bladder, a comprehensive review of the literature related to the evolution of the concept, epidemiology, diagnosis, and management was conducted. This text corresponds to the first part of the review Overactive Bladder 18-years.Univ Fed Sao Paulo, EPM, Rua Dr Oscar Monteiro Barros 617-141, BR-05641010 Sao Paulo, SP, BrazilUniv Sao Paulo, Dept Urol, BR-05508 Sao Paulo, SP, BrazilFac Med ABC, Dept Urol, Sao Paulo, SP, BrazilUniv Los Andes, Dept Urol, Bogota, ColombiaEscuela Med, Dept Urol, Mexico City, DF, MexicoHosp Clin Jose San Martin, Catedra Urol, Buenos Aires, DF, ArgentinaMae de Deus Ctr Hosp, Dept Urol, Porto Alegre, RS, BrazilUniv Fed Ciencias Saude Porto Alegre, Porto Alegre, RS, BrazilAC Camargo Hosp, Dept Urol, Sao Paulo, BrazilHosp Clin Fuerza Area Chile, Santiago, ChileInst Mexicano Seguro Social, Mexico City, DF, MexicoHosp Souza Aguiar, Dept Urol, Rio De Janeiro, RJ, BrazilComplejo Med Policial Churruca Visca, Serv Urol, Buenos Aires, DF, ArgentinaCtr Policlin Valencia Vina, Valencia, VenezuelaHosp Pablo Tobon Uribe, Medellin, ColombiaClin Indisa, Serv Urol, Providencia, ChileCtr Reabilitacao & Readaptacao Dr Henriqe Santill, Goiania, Go, BrazilHosp Univ Caracas, Serv Urol, Caracas, VenezuelaUniv Fed Ceara, Div Urol, Fortaleza, Ceara, BrazilUniv Fed Sao Paulo, EPM, Rua Dr Oscar Monteiro Barros 617-141, BR-05641010 Sao Paulo, SP, BrazilWeb of Scienc

Effect of nitric oxide deficiency and the action of sildenal in lower urinary tract : an experimental study in rats

Orientadores: Carlos Arturo Levi D'Ancona, Edson AntunesTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias MedicasResumo: Sintomas do trato urinário inferior (STUI) estão associados com a piora da Qualidade de Vida dos pacientes e geram custos substanciais para a sociedade. Nos últimos anos houve aumento no conhecimento da fisiopatologia e história natural do STUI e obstrução benigna da próstata (OBP). O óxido nítrico (NO) tem sido implicado como neurotransmissor em vários sítios do sistema nervoso de mamíferos, incluindo as sinapses periféricas do trato urogenital em homens. Estudos recentes avaliaram os efeitos dos inibidores da enzima fosfodiesterase tipo 5 (PDE5) em pacientes com STUI secundário à OBP e observou-se melhora dos sintomas. Como, atualmente, não se sabe o exato papel da sildenafila no tratamento da disfunção miccional associado à OBP foi sugerido em um desses estudos que novas bases fisiopatológicas seriam necessárias para avaliar o efeito do inibidor da fosfodiesterase no trato urinário inferior. Objetivos: Os objetivos deste estudo foram determinar os efeitos urodinâmicos da inibição da síntese de óxido nítrico pela N-nitro-L-arginina metil éster (L-NAME), bem como a ação da sildenafila no trato urinário inferior de ratos com deficiência crônica de NO. Materiais e Métodos: No estudo foram utilizados 27 ratos da espécie Wistar que foram submetidos a estudo urodinâmico, sendo nove controles (Grupo 1), oito tratado com L-NAME (60mk/Kg/dia dissolvido em água) por 30 dias (Grupo 2), quatro tratados somente com sildenafila (100µg/Kg intravenoso) (Grupo 3) e seis tratados com L-NAME por 30 dias seguidos de administração aguda de sildenafila intravenoso(100µg/Kg) (Grupo 4). Resultados: A administração crônica e sistêmica de L-NAME resultou em aumento significativo no número de contrações não associado à micção (0,98 ±0,75 versus 2,71 ±0,89), limiar de volume (1,26 ±0,38 versus 2,8 ±1,64) e frequência dos ciclos de micção (1,2 ±0,65 versus 1,79 ±0,78), comparando Grupos 1 e 2, respectivamente. A administração intravenosa de sildenafila para os animais do Grupo 3 não alterou a frequência (pré-sildenafila 1,23 ±0,37 versus pós-sildenafila 1,3 ±0,15) e a amplitude dos ciclos de micção (pré-sildenafila 8,5 ±3,16 versus pós-sildenafila 9,0 ±2,99). Foi encontrada diferença significativa entre os Grupos 3 e 4 em relação a frequência dos ciclos de micção após administração da sildenafila (1,3 ±0,15 versus 0,35 ±0,25). A amplitude, antes da administração da sildenafila foi maior no Grupo 4 (8,50 ±3,16 versus 27,0 ±8,73; Grupos 3 e 4, respectivamente), porém tornou-se semelhante aos animais do Grupo 3 após a sildenafila (9,0 ±2,99 versus 7,5 ±6,6; Grupos 3 e 4, respectivamente). Conclusões: A redução sistêmica de óxido nítrico promove contrações involuntárias do detrusor e ciclos de micção de menor intervalo. A administração da sildenafila, em animais com deficiência crônica de óxido nítrico, promove diminuição do número de ciclos de micção e da amplitude das contrações.Abstract: The lower urinary tract symptoms (LUTS) are associated with a worsening in patients' Quality of Life and lead to substantial costs for society. There is a special interest in the development of effective treatment options, with low morbidity, for detrusor overactivity (DO) secondary to benign prostatic obstruction (BPO). Nitric oxide (NO) has been involved as a neurotransmitter in several sites of the nervous system of mammals, including peripheral synapses of the urogenital tract. Sildenafil has been used in the clinical treatment of men with LUTS associated with BPO, with improvement in symptoms. However, this is just one assumption as it has not been proven by experimental studies and the precise role of sildenafil in the treatment of voiding dysfunction associated with BPO is not known. Objective: The aims of this study were evaluate the urodynamic effects of nitric oxide inhibition synthesis by N-nitro-L-arginine methyl ester (L-NAME), as well the action of sildenafil in the lower urinary tract of rats with chronic deficiency of nitric oxide.Materials and Methods: Twenty-seven adult Wistar rats underwent anesthetized cystometrograms: nine controls (Group 1), eight treated with oral L-NAME (60mg/kg/day dissolved in drinking water) for 30 days (Group 2), four treated with sildenafil only (100µg/kg intravenously, IV) (Group 3) and six treated with oral L-NAME for 30 days followed by acute IV sildenafil (100µg/Kg ) (Group 4). Results: The chronic and systemic administration of L-NAME resulted in a significant increase in non voiding contractions (0,98 ±0,75 versus 2,71 ±0,89), volume threshold (1,26 ±0,38 versus 2,8 ±1,64) and frequency of micturition cycles (1,2 ±0,65 versus 1,79 ±0,78), comparing Groups 1 e 2, respectively. The others parameters were not differences. The intravenous administration of sildenafil to Group 3 animals did not significantly alter the frequency (pre-sildenafil 1,23 ±0,37 versus post-sildenafil 1,3 ±0,15) or amplitude of micturition cycles (pre-sildenafil 8,5 ±3,16 versus post-sildenafila 9,0 ±2,99). A significant difference was found between the groups in relation to: void cycles after administration of sildenafil (1,3 ±0,15 versus 0,35 ±0,25). The amplitude before administration was large in Group 4 (8,50 ±3,16 versus 27,0 ±8,73; Groups 3 e 4, respectively), however become similar to that of the Group 3 animals after sildenafil (9,0 ±2,99 versus 7,5 ±6,6; Groups 3 e 4, respectively). Conclusion: The systemic reduction of nitric oxide increase non voiding contractions and frequency of micturition cycles. The administration of sildenafil in animals with chronic deficiency of nitric oxide decreases the number of micturition cycles as well as the contractions amplitude.DoutoradoCirurgiaDoutor em Cirurgi