Emodin inhibits bladder inflammation and fibrosis in mice with interstitial cystitis by regulating JMJD3

Purpose: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a devastating urological chronic pelvic pain condition. In search of a potential treatment, we investigated the effect of emodin on IC/BPS inflammation and fibrosis, and explore the potential mechanism. Methods: An experimental model of interstitial cystitis was induced by cyclophosphamide, and human bladder smooth muscle cells were treated with lipopolysaccharide to establish the cell model in vitro. In both models, inflammation- and fibrosis-related indexes were measured after emodin administration. Furthermore, the specific antagonists were used to dig for the mechanisms underlying the response to emodin treatment. Results: Emodin significantly ameliorated management of cystitis, reduced the amount of inflammatory cytokines (tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-1ß, interleukin-8, and interleukin-6) in models, as well as reducing the synthesis of fibrosis marker including collagen1, collagen3, vimentin, fibronectin and α-smooth muscle actin. Further mechanism studies demonstrated that emodin inhibited inflammatory reaction and fibrosis through blocking lysine-specific demethylase 6B (JMJD3) expression via JAK/STAT, NF-κB and TGF-ß/SMAD pathways. Conclusions: Our study reveals the critical role of emodin-JMJD3 signaling in interstitial cystitis by regulating inflammation, fibrosis, and extracellular matrix deposition in cells and tissues, and these findings provide an avenue for effective treatment of patients with cystitis.

Aspectos psicológicos asociados a la cistitis intersticial / Psychological aspects associated with interstitial cystitis

La cistitis intersticial o síndrome de vejiga dolorosa es un padecimiento complejo asociado a dolor pélvico intenso con síntomas urinarios como urgencia, polaquiuria, dispareunia, incontinencia y nicturia, que afecta de manera importante la calidad de vida y las relaciones sociales y productivas del paciente. La evidencia muestra que el abordaje de los factores psicosociales que afectan a los pacientes con esta enfermedad es esencial. El tratamiento debe ir más allá de los síntomas clínicos y considerar los aspectos individuales de cada paciente, su salud mental, sus experiencias de vida y su comorbilidad, dado que los trastornos psicológicos como la ansiedad, la depresión y el estrés postraumático pueden influir en la manera en que se percibe el dolor, y están ligados con la gravedad y el empeoramiento de los síntomas. La literatura presenta a la intervención psicológica desde el enfoque cognitivo conductual como un medio para disminuir el dolor, la ansiedad y el catastrofismo, dando al paciente herramientas que le permitan obtener una sensación de control a partir del afrontamiento y mejorar su calidad de vida.

Interstitial cystitis or painful bladder syndrome is a complex condition associated with intense pelvic pain with urinary symptoms such as urgency, pollakiuria, dyspareunia, incontinence and nocturia that significantly affects the patient's quality of life, social and productive relationships. Evidence shows that addressing the psychosocial factors that affect patients with this disease is essential. Treatment should go beyond clinical symptoms and consider the individual aspects of each patient, their mental health, life experiences and comorbidities, since psychological disorders such as anxiety, depression and post-traumatic stress disorder can influence the way pain is perceived and are linked to the severity and worsening of symptoms. The literature presents psychological intervention from the cognitive-behavioral approach to reduce pain, anxiety and catastrophism, giving the patient tools that allow him to obtain a sense of control from coping tools that allow him to improve his quality of life.

Exploration of the core genes in ulcerative interstitial cystitis/bladder pain syndrome

ABSTRACT Objective: Interstitial cystitis (IC)/bladder pain syndrome (BPS) is a chronic inflammatory disease that can cause bladder pain and accompanying symptoms, such as long-term urinary frequency and urgency. IC/BPS can be ulcerative or non-ulcerative. The aim of this study was to explore the core genes involved in the pathogenesis of ulcerative IC, and thus the potential biomarkers for clinical treatment. Materials and Methods: First, the gene expression dataset GSE11783 was downloaded using the Gene Expression Omnibus (GEO) database and analyzed using the limma package in R to identify differentially expressed genes (DEGs). Then, the Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for Gene Ontology (GO) functional analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) was used for pathway enrichment analysis. Finally, the protein-protein interaction (PPI) network was constructed, and key modules and hub genes were determined using the STRING and Cytoscape software. The resulting key modules were then analyzed for tissue-specific gene expression using BioGPS. Results: A total of 216 up-regulated DEGs and 267 down-regulated genes were identified, and three key modules and nine hub genes were obtained. Conclusion: The core genes (CXCL8, CXCL1, IL6) obtained in this study may be potential biomarkers of interstitial cystitis with guiding significance for clinical treatment.

Intravesical Glycosaminoglycans Experience for Chronic Lower Urinary Tract Pathology Treatment / Experiencia con glucosaminoglicanos intravesicales para el tratamiento de patologías crónicas del tracto urinario inferior

Objective Intravesical glycosaminoglycans (GAG) treatment is one of the therapeutic options for chronic bladder pathologies and is approved for Bladder Pain Syndrome (BPS), radiation cystitis, and recurrent urinary tract infections (UTIs). The purpose of this study is to describe the demographic characteristics of patients with such pathologies in our population and to evaluate treatment response. Methods It is a retrospective study of patients with the aforementioned pathologies, who received treatment with GAG. Demographic characteristics and subjective improvement with treatment were evaluated. A bivariate analysis was performed to study possible improvement predictors. Results 53 patients were evaluated. Of them, 33 (62.3%) with BPS, 12 (22.6%) with recurrent UTIs, and 8 (15.1%) with radiation cystitis. The dose range received was between 4 - 20 instillations, with a median of 6 doses. 67.9% of patients showed improvement of symptoms with treatment, this percentage being even higher for the group of patients with recurrent UTIs (91%). No treatment response predictors were found. Conclusions Intravesical GAG treatment is a therapeutic alternative for patients with chronic bladder pathologies, with satisfactory results in the medium term. Prospective studies are needed to support the findings of this study.

Objetivo El tratamiento con glucosaminoglicanos intravesicales hace parte de las opciones terapéuticas de las patologías crónicas de la vejiga y se encuentra aprobado para el tratamiento de síndrome de vejiga dolorosa (SVD), cistitis por radiación e infección urinaria recurrente. El objetivo de este estudio es describir las características demográficas de los pacientes con dichas patologías en nuestra población y evaluar la respuesta al tratamiento. Métodos Estudio retrospectivo de pacientes con las patologías mencionadas, quienes recibieron tratamiento con glucosaminoglicanos. Se evaluaron las características demográficas y la respuesta al tratamiento. Se realizó un análisis bivariado para estudiar posibles variables predictoras de mejoría. Resultados Se evaluaron 53 pacientes. De estos, 33 (62.3%) con síndrome de vejiga dolorosa, 12 (22.6%) con infección urinaria recurrente y 8 (15.1%) con cistitis por radiación. El rango de dosis recibida estuvo entre 4-20 instilaciones, con una mediana de 6 dosis. El 67.9% de los pacientes tuvo una respuesta adecuada al tratamiento, siendo este porcentaje aún mayor para el grupo de pacientes con IVU recurrente (91%). No se encontraron factores predictores de respuesta al tratamiento. Conclusiones El tratamiento con GAG intravesicales es una alternativa terapéutica para pacientes con patologías crónicas de la vejiga, con resultados satisfactorios a mediano plazo. Se necesitan estudios prospectivos que soporten los hallazgos de este trabajo.

Interstitial cystitis - intravesical treatment

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.

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.

Systematic review of oral therapy for the treatment of symptoms of bladder pain syndrome: The brazilian guidelines / Revisão sistemática sobre terapia oral para tratamento dos sintomas da síndrome da bexiga dolorosa: as diretrizes brasileiras

Abstract Interstitial cystitis (IC), including bladder pain syndrome (BPS), is a chronic and debilitating disease thatmainly affectswomen. It is characterized by pelvic pain associated with urinary urgency, frequency, nocturia and negative urine culture,with normal cytology. In 2009, the Society for Urodynamics and Female Urology (SUFU) defined the term IC/BPS as an unpleasant sensation (pain, pressure, and discomfort) perceived to be related to the urinary bladder, associated with lower urinary tract symptoms for more than 6 weeks duration, in the absence of infection or other identifiable causes. This is the definition used by the American Urological Association (AUA) in the most recent guidelines on IC/BPS. Interstitial cystitis may be sufficiently severe to have a devastating effect on the quality of life, but it may also be associated with moderate symptoms whose effects are less debilitating. Although there are several clinical trials to assess oral and intravesical therapies, the treatment for IC remains far from ideal. This systematic assessment evaluates published randomized clinical trials on oralmedications used totreat symptoms of BPS. This studywas performed according to the preferred reporting items for systematic reviews and metaanalyses (PRISMA)method. Two independent reviewers screened the studies to determine their inclusion or exclusion and to perform the methodological analysis. The inclusion criteria included randomized studiespublishedbetween April of 1988and April of2016 that used oral medications to treat symptoms of BPS or IC. According to the systematic review performed,we should consider pentosan polysulfate as one of the bestoptions of oral drugs for the treatment of BPS symptoms. However, this drug is not an available option in Brazil. Orally administered amitriptyline is an efficacious medical treatment for BPS, and it should be the first treatment offered.

Resumo Cistite intersticial (IC), incluindo a síndrome da bexiga dolorosa (SBD), é uma doença crônica e debilitante que afeta principalmente mulheres. É caracterizada por dor pélvica associada à urgência miccional, frequência urinária, noctúria e exame cultural de urina negativo, com citologia normal. A cistite intersticial pode ser suficientemente severa para ter um efeito devastador na qualidade de vida, mas também pode estar associada a sintomas moderados e menos debilitantes. Embora existam vários ensaios clínicos para avaliar terapias orais e intravesicais, o tratamento para IC permanece longe do ideal. Esta revisão sistemática avaliou ensaios clínicos randomizados publicados sobre medicamentos orais usados para tratar sintomas de SBD. Este estudo foi realizado de acordo com ométodo preferred reporting items for systematic reviews and meta-analyses (PRISMA). Dois revisores independentes examinaram os estudos para determinar sua inclusão ou exclusão e para realizar a análise metodológica. Os critérios de inclusão foram: ensaios clínicos randomizados publicados entre abril de 1988 e abril de 2016 que usaram medicações orais no tratamento dos sintomas da SBD ou CI. De acordo com a revisão sistemática realizada, a melhor opção de medicação oral para o tratamento dos SBD é o pentosano polissulfato sódico. No entanto, esta droga não está disponível no Brasil. A amitriptilina administrada por via oral é um tratamento eficaz para SBD e deve ser oferecida como primeira escolha.

A prospective randomized controlled multicentre trial comparing intravesical DMSO and chondroïtin sulphate 2% for painful bladder syndrome/interstitial cystitis

ABSTRACT Objective To compare effectiveness of intravesical chondroïtin sulphate (CS) 2% and dimethyl sulphoxide (DMSO) 50% in patients with painful bladder syndrome/interstitial cystitis (PBS/IC). Materials and methods Patients were randomized to receive either 6 weekly instillations of CS 2% or 50% DMSO. Primary endpoint was difference in proportion of patients achieving score 6 (moderately improved) or 7 (markedly improved) in both groups using the Global Response Assessment (GRA) scale. Secondary parameters were mean 24-hours frequency and nocturia on a 3-day micturition dairy, changes from baseline in O’Leary-Sant questionnaire score and visual analog scale (VAS) for suprapubic pain. Results Thirty-six patients were the intention to treat population (22 in CS and 14 in DMSO group). In DMSO group, 57% withdrew consent and only 6 concluded the trial. Major reasons were pain during and after instillation, intolerable garlic odor and lack of efficacy. In CS group, 27% withdrew consent. Compared with DMSO group, more patients in CS group (72.7% vs. 14%) reported moderate or marked improvement (P=0.002, 95% CI 0.05-0.72) and achieved a reduction in VAS scores (20% vs. 8.3%). CS group performed significantly better in pain reduction (-1.2 vs. -0.6) and nocturia (-2.4 vs. -0.7) and better in total O’Leary reduction (-9.8 vs. -7.2). CS was better tolerated. The trial was stopped due to high number of drop-outs with DMSO. Conclusions Intravesical CS 2% is viable treatment for PBS/IC with minimal side effects. DMSO should be used with caution and with active monitoring of side effects. More randomized controlled studies on intravesical treatments are needed.

Análise das propriedades psicométricas dos instrumentos "The Interstitial Cystitis Symptom Index and Problem Index" e "Pelvic Pain and Urgency/Frequency (PUF) Patient Symptom Scale" e da qualidade de vida de pacientes com cistite intersticial / Analysis of psychometric properties of the instruments "The Interstitial Cystitis Symptom Index and Problem Index" and "Pelvic Pain and Urgency/Frequency (PUF) Patient Symptom Scale" and quality of life of patients with interstitial cystitis

Objetivou-se avaliar a confiabilidade e validade convergente entre os questionários "The Interstitial Cystitis Symptom Index and Problem Index" (The O'Leary-Sant) e "Pelvic Pain and Urgency/Frequency (PUF) Patient Symptom Scale"; verificar quais são as disfunções sexuais em pacientes com CI, identificar suas possíveis causas, verificar os instrumentos de avaliação de qualidade de vida, disfunção sexual e grau da doença e identificar os tratamentos recomendados para esse problema, além de traduzir, adaptar para a cultura brasileira e analisar a confiabilidade e a validade convergente da "Bladder Symptom Impact Scale ¿ BSI-6" utilizada em pacientes com cistite intersticial. Essa tese é composta por dois tipos de estudo: um estudo metodológico de tradução e adaptação cultural, seguindo as etapas metodológicas de tradução, síntese, retrotradução, comitê de especialistas e pré-teste, bem como, análise de confiabilidade de teste-reteste, consistência interna e validade de constructo convergente que envolveu os questionários The O'Leary-Sant, PUF e BSI-6. O segundo tipo de estudo foi uma revisão integrativa da literatura que incluiu 19 publicações relacionadas a disfunção sexual em mulheres com cistite intersticial, mediante pesquisa realizada nas bases de dados: PubMed, Embase, CINAHL e PEDro. As fases de tradução, síntese das traduções e retrotradução da Bladder Symptom Impact Scale ¿ BSI-6, que avalia a qualidade de vida em pessoas com cistite intersticial, foram finalizadas satisfatoriamente e a avaliação das versões síntese pelo comitê de especialistas resultou em algumas alterações, assegurando as equivalências entre a versão original e traduzida. Devido à necessidade de modificações em decorrência da baixa escolaridade da população, o instrumento foi pré-testado duas vezes no total de 35 sujeitos com sintomas de cistite intersticial. O instrumento, após as alterações, demonstrou ser de fácil compreensão e rápido preenchimento. A confiabilidade foi avaliada por meio da consistência interna medida pelo alfa de Cronbach, com resultado geral de: 0,92 e a validade de constructo convergente foi medida por meio da correlação com o The O'Leary-Sant e medida pelo coeficiente de correlação de Spearman e se mostrou alta. A confiabilidade de teste-reteste para os questionários "The O'Leary-Sant" e "PUF" apresentou valores superiores a 0,80, sugerindo excelente confiabilidade. A consistência interna se mostrou boa para ambos, apresentando valores superiores a 0,70. A correlação entre os dois questionários expressa pelo coeficiente de correlação de Spearman se mostrou elevada. Os estudos analisados na revisão integrativa da literatura apontaram a dispareunia e vulvodinia como os principais problemas sexuais de mulheres com CI. As principais causas desses problemas são hipertonia da musculatura do assoalho pélvico e história prévia de abuso sexual. Concluiu-se que, os questionários "The Interstitial Cystitis Symptom Index and Problem Index" e "Pelvic Pain and Urgency/Frequency (PUF) Patient Symptom Scale" se mostraram confiáveis e válidos para serem aplicados em pacientes com CI, auxiliando o seu diagnóstico; que a aplicação de uma meticulosa metodologia permitiu a produção de uma versão da Bladder Symptom Impact Scale ¿ BSI-6, em português, fiel à original, confiável e válida que poderá ser utilizada para a avaliar a qualidade de vida de pessoas com cistite intersticial e, por fim, os estudos mostram que mulheres com CI e que possuem disfunção sexual devem ser tratadas por uma equipe multiprofissional a fim de melhorar os sintomas da doença e, consequentemente, a qualidade de vida, assim sendo, os instrumentos para diagnóstico e avaliação da qualidade de vida traduzidos e validados poderão ser úteis para esse fim. (AU)

This study aimed to assess the reliability and convergent validity of the questionnaires "The Interstitial Cystitis Symptom Index and Problem Index" (The O'Leary-Sant) and "Pelvic Pain and Urgency / Frequency (PUF) Patient Symptom Scale"; check what are the sexual dysfunctions in patients with IC, identify possible causes, check the instruments for assessing quality of life, sexual dysfunction and degree of the disease and identify the recommended treatments for this problem, as well as to translate, adapt to the Brazilian culture and analyze the reliability and convergent validity of the "Bladder Symptom Impact Scale - BSI-6" used in patients with interstitial cystitis. This thesis is composed of two types of studies: a methodological study of translation and cultural adaptation, following the methodological steps of translation, synthesis, back translation, expert committee and pre-test and test-retest reliability analysis, consistency internal and convergent construct validity involving the questionnaires The O'Leary-Sant, PUF and BSI-6. The second type of study is an integrative literature review that included 19 publications related to sexual dysfunction in women with interstitial cystitis, by research conducted in the databases PubMed, Embase, CINAHL and PEDro. The phases of translation, synthesis of translations and back translation of Bladder Symptom Impact Scale - BSI-6, which evaluates the quality of life in people with interstitial cystitis, were completed satisfactorily and the evaluation of versions synthesis by the expert committee resulted in some changes, ensuring the equivalence between the original and translated version. Due to the need for changes due to the low educational level of the population, the instrument was pre-tested twice in the total of 35 subjects with symptoms of interstitial cystitis. The instrument, after the changes proved to be easy to understand and quick filling. Reliability was assessed by internal consistency measured by Cronbach's alpha, with the overall result of: 0.92 and convergent construct validity was measured by correlating with The O'Leary-Sant and measured by the correlation coefficient Spearman and showed high. The test-retest reliability for the questionnaire "The O'Leary-Sant" and "PUF" presented values greater than 0.80, suggesting excellent reliability. The internal consistency proved to be good for both, with values above 0.70. The correlation between the two questionnaires expressed by the Spearman correlation coefficient showed high. The studies that analyzed the integrative literature review showed dyspareunia and vulvodynia as the main sexual problems in women with IC. The main causes of these problems are hypertonia of the pelvic floor muscles and a history of sexual abuse. It was concluded that questionnaires "The Interstitial Cystitis Symptom Index and Problem Index" and "Pelvic Pain and Urgency / Frequency (PUF) Patient Symptom Scale" proved to be reliable and valid to be used in patients with IC, supporting the diagnosis; that the application of a meticulous methodology enabled the production of a version of the Bladder Symptom Impact Scale - BSI-6 in Portuguese, faithful to the original, and proved to be reliable and valid and can be used to assess the quality of life of people with interstitial cystitis and finally, studies show that women who have sexual dysfunction should be treated by a multidisciplinary team in order to ameliorate the symptoms of the disease and, consequently, the quality of life, therefore, the tools for diagnosis and assessment of quality of life translated and validated may be useful for this purpose.(AU)

The use of neurovascular ultrasound versus digital subtraction angiography in acute ischemic stroke / O uso do ultrassom neurovascular comparado a angiografia digital no AVC isquêmico agudo

Cervical and intracranial arterial evaluation is an important issue for acute ischemic stroke (IS). Objective Compare the use of the neurovascular ultrasound examination (NVUE) to digital subtraction angiography (DSA) in acute IS patients for diagnosing significant extracranial and intracranial arteriopathy. Method Nonconsecutive patients with IS or transient ischemic attack admitted within 12 hours of the onset of symptoms were evaluated retrospectively. Standardized NVUE and DSA were done in all patients within the first 120 hours of hospital admission. Results Twenty-four patients were included in the study. Compared to DSA, the NVUE demonstrated 94.7% sensitivity and 100% specificity for identifying symptomatic extracranial and/or intracranial arteriopathy. Conclusion The standardized NVUE technique demonstrated high sensitivity and specificity compared to DSA for diagnosing arterial abnormalities in acute IS patients. .

A avaliação cervical e intracraniana é uma etapa importante no AVC isquêmico (AVCi) agudo. Objetivo Comparar o uso do ultrassom neurovascular (USNV) com técnica padronizada e a angiografia digital (AD) em paciente com AVCi agudo no diagnóstico de doença arterial significativa extra e/ou intracraniana. Método Pacientes com AVCi e AIT admitidos em até 12 horas do início dos sintomas foram retrospectivamente avaliados. Todos os pacientes foram submetidos a USNV e AD padronizado em até 120 horas da admissão. Resultados Vinte e quatro pacientes foram incluídos no estudo. Em comparação com a AD, o USNV apresentou sensibilidade de 94,7% e especificidade de 100% para o diagnóstico de doença arterial significativa extra e/ou intracraniana. Conclusão O uso de técnica padronizada de USNV demonstrou elevada sensibilidade e especificidade para o diagnóstico de doença arterial significativa extra e intracraniana quando comparado a AD. .

Estudio piloto de eficacia de imipramina en el tratamiento del síndrome de dolor vesical / Pilot study of the effectiveness of imipramine in the treatment of bladder pain syndrome

El síndrome de dolor vesical (SDV) es un cuadro que forma parte del dolor pelviano crónico (DPC), donde el origen del dolor esta en mecanismos de neuromodulación. En este sentido, los antidepresivos tricíclicos (ATC), especialmente amitriptilina, son la terapia de primera línea. Sin embargo, los efectos adversos dificultan la adherencia a la terapia. Imipramina, otro ATC, presenta menores efectos adversos, aunque su eficacia no ha sido evaluada en SDV. Objetivo: Evaluar la eficacia de imipramina en el tratamiento de SDV en un estudio piloto. Metodología: Veinte pacientes con diagnóstico de SDV, fueron tratadas con imipramina 25 mg cada 8 horas vía oral durante 30 días. Se evaluó intensidad de dolor según EVA antes y al término del tratamiento. Además se evaluó sintomatología urinaria utilizando el cuestionario PUF. Resultados: Diecinueve pacientes completaron el tratamiento. Una paciente abandonó el tratamiento por síntomas gastrointestinales. Ocho de 19 pacientes mostraron una mejoría total del dolor al término del tratamiento. Tres pacientes más lograron una respuesta completa con 3 meses de tratamiento con imipramina. La intensidad del dolor según EVA y la puntuación en el cuestionario PUF mejoraron significativamente al término del tratamiento. Efectos secundarios a imipramina fueron referidos por 4 de 19 pacientes, y fueron menores. Conclusión: Imipramina mostró ser una terapia efectiva en el manejo de SDV, con efectos adversos menores. Se requieren estudios comparativos con mayor número de pacientes para considerar su utilidad clínica en el manejo del SDV...

Bladder pain syndrome (BPS) is a symptom which is part of chronic pelvic pain (CPP), where the origin of the pain is in the neuromodulation mechanisms. In this context, tricyclic antidepressants (TCAs), especially amitriptyline, are a first line therapy. However, adverse effects make continuing with the therapy difficult. Imipramine, another TCA, has lesser adverse effects, although its effectiveness has not been evaluated in BPS. Objective: Evaluate the effectiveness of imipramine in the treatment of BPS in a pilot study. Methodology: Twenty patients with a diagnosis of BPS were treated taking 25 mg of imipramine orally every 8 hours, for 30 days. The intensity of the pain following PIS was evaluated before and after the treatment. In addition, the urinary symptomatology was evaluated using the PUF questionnaire. Results: Nineteen patients completed the treatment. One patient abandoned the treatment due to gastrointestinal symptoms. Eight of the 19 patients had completely recovered at the end of the treatment. Three other patients achieved a complete recovery after 3 months of treatment with imipramine. The intensity of the pain following the PIS, and the score on the PUF questionnaire, significantly improved by the end of the treatment. Secondary effects to imipramine were referred by 4 of the 19 patients, and these were minor. Conclusion: Imipramine was shown to be an effective therapy for dealing with BPS, with minor adverse effects. Comparative studies are required with a higher number of patients to consider its clinical use in the handling of BPS...

Evaluation of the metabolism of glycosaminoglycans in patients with interstitial cystis

Introduction: Painful bladder syndrome/interstitial cystitis (PBS/IC) pathogenesis is not fully known, but evidence shows that glycosaminoglycans (GAG) of bladder urothelium can participate in its genesis. The loss of these compounds facilitates the contact of urine compounds with deeper portions of bladder wall triggering an inflammatory process. We investigated GAG in urine and tissue of PBS/IC and pure stress urinary incontinence (SUI) patients to better understand its metabolism. Materials and Methods: Tissue and urine of 11 patients with PBS/IC according to NIDDK criteria were compared to 11 SUI patients. Tissue samples were analyzed by histological, immunohistochemistry and immunofluorescence methods. Statistical analysis were performed using t Student test and Anova, considering significant when p < 0.05. Results: PBS/IC patients had lower concentration of GAG in urine when compared to SUI (respectively 0.45 ± 0.11 x 0.62 ± 0.13 mg/mg creatinine, p < 0.05). However, there was no reduction of the content of GAG in the urothelium of both groups. Immunofluorescence showed that PBS/IC patients had a stronger staining of TGF-beta, decorin (a proteoglycan of chondroitin/dermatan sulfate), fibronectin and hyaluronic acid. Conclusion: the results suggest that GAG may be related to the ongoing process of inflammation and remodeling of the dysfunctional urothelium that is present in the PBS/IC. .

Adaptação à cultura brasileira dos questionários The O'Leary-Sant e PUF, usados para cistite intersticial / Adaptation of the O'Leary-Sant and the PUF for the diagnosis of interstitial cystitis for the Brazilian culture / Adaptación a la cultura brasileña de los cuestionarios The O'Leary-Sant y Puf, usados para cistitis intersticial

O objetivo deste estudo foi traduzir e adaptar à cultura brasileira os instrumentos The O'Leary-Sant e PUF, utilizados no diagnóstico de cistite intersticial. Foram realizadas as etapas metodológicas recomendadas pela literatura internacional para a adaptação cultural. As etapas de tradução, síntese das traduções e retrotradução foram realizadas satisfatoriamente, e a avaliação das versões sintéticas pelo comitê de especialistas resultou em algumas alterações, assegurando as equivalências entre as versões originais e traduzidas. O PUF foi pré-testado entre 40 sujeitos e The O'Leary-Sant em uma amostra de 50 indivíduos, devido à necessidade de ajustes em decorrência da baixa escolaridade da população. O processo de tradução e adaptação foi realizado com sucesso e os instrumentos, após as modificações, demonstraram ser de fácil compreensão e rápido preenchimento. Entretanto, este é um estudo que antecede o processo de validação e será premente o emprego do instrumento em novas pesquisas para que sejam avaliadas suas propriedades psicométricas.

The aim of this study was to translate and adapt the instruments known as The O'Leary-Sant and PUF to the Brazilian culture used in the diagnosis of interstitial cystitis. We followed the methodological steps recommended by the international literature for cultural adaptation. The steps of translation, synthesis of translations and back translation were performed satisfactorily and evaluation the versions of the synthesis by the panel of experts has resulted in some changes, ensuring the equivalence between the original and translated versions. The PUF was pretested among 40 subjects and The O'Leary-Sant in a sample of 50 individuals due to the need for adjustments due to the low education population. The translation and adaptation process was successful and the instruments, after some modifications, proved easy to understand and complete quickly. However, this is a study prior to the validation process and will be promoting the use of the instrument in new research to assess its measurement properties.

Se objetivó traducir y adaptar a la cultura brasileña los instrumentos The O'Leary-Sant y PUF, utilizados para diagnosticar cistitis intersticial. Fueron efectuadas las etapas metodológicas recomendadas por la literatura internacional para adaptación cultural. Las etapas de traducción, síntesis de traducciones y retrotraducción se realizaron satisfactoriamente, la evaluación de las versiones sintetizadas por parte del comité de especialistas derivó en algunas alteraciones, asegurando las equivalencias entre versiones originales y traducidas. El PUF fue pre-testeado con 40 sujetos y The O'Leary-Sant en muestra de 50 individuos, por la necesidad de ajustes derivados de la baja escolarización de la población. El proceso de traducción y adaptación se efectuó con suceso y los instrumentos luego de las modificaciones demostraron ser de sencilla comprensión y rápido completado. Sin embargo, este estudio es previo al proceso de validación, será imprescindible el uso del instrumento en nuevas investigaciones para evaluar sus propiedades psicométricas.

Síndrome da dor vesical/cistite intersticial: aspectos atuais / Bladder pain syndrome/interstitial cystitis: current aspects

Síndrome da dor vesical é a nomenclatura proposta para substituir o termo antigamente conhecido como cistite intersticial. Deve ser diagnosticada com base nas queixas de dor, pressão ou desconforto pélvico crônico, relacionados à bexiga acompanhados por pelo menos outro sintoma urinário como urgência ou aumento de frequência. A prevalência estimada é de 300 por 100.000 mulheres. A etiologia e a fisiopatologia ainda não foram elucidadas, mas mecanismos neurológicos centrais, fatores genéticos, imunológicos e infecciosos parecem estar envolvidos. O diagnóstico é de exclusão e deve ser baseado nos sintomas. O teste com cloridrato de potássio intravesical não deve ser usado como ferramenta diagnóstica. A cistoscopia com hidrodistensão e biópsia auxilia na documentação e classificação da doença. O tratamento deverá ser multidisciplinar e multimodal, associando-se medicações orais com intravesicais, modificações na dieta e no estilo de vida e medidas não farmacológicas

Bladder pain syndrome is the nomenclature proposed to replace the term formerly known as interstitial cystitis. It should be diagnosed based on complaints of pain, chronic pelvic pressure or discomfort related to bladder accompanied by at least one other urinary symptom, such as urgency or increased frequency. The estimated prevalence is 300 per 100,000 women. The etiology and pathophysiology have not been elucidated, but central neurologic mechanisms, genetic, immunological and infectious factors seem to be involved. The diagnosis is by exclusion and should be based on symptoms. The test with intravesical potassium chloride should not be used as a diagnostic tool. Cystoscopy with hydrodistenstion and biopsy assist in the documentation and classification of the disease. Treatment should be multidisciplinary and multimodal, associating intravesical and oral medications, changes in diet and in lifestyle and nonpharmacological measures

Papel de la cistoscopia en el estudio de las pacientes con dolor pélvico crónico: estudio observacional / The role of cystoscopy when studying patients suffering from chronic pelvic pain: an observational study

Objetivo: este estudio busca describir los hallazgos cistoscópicos en un grupo de pacientes con dolor pélvico crónico (DPC) que consultaron a una clínica de referencia en Pereira (Colombia). Materiales y métodos: es un estudio de corte transversal en mujeres que consultaron la clínica en el período comprendido entre julio de 2006 y octubre de 2008, por dolor pélvico crónico a una institución hospitalaria de 4° nivel y centro de remisión; y que fueron sometidas a laparoscopia y cistoscopia. Por medio de un formulario se extrajeron los datos de las historias clínicas. También se describe la prevalencia de cistitis intersticial y trigonitis crónica. Resultados: 115 mujeres con DPC fueron sometidas a laparoscopia y cistoscopia bajo anestesia general. El 59% de las pacientes tenían hallazgos cistoscópicos de cistitis intersticial. Los síntomas de frecuencia urinaria aumentada, disuria y nicturia tuvieron una correlación estadísticamente significativa con los hallazgos anormales en la cistoscopia. El principal signo hallado en el examen físico fue el dolor al palpar la vejiga. El test de cloruro de potasio tuvo una sensibilidad del 71%, una especificidad del 44%, un Valor Predictivo Positivo (VPP) del 60% y un Valor Predictivo Negativo (VPN) del 57%. Conclusiones: en pacientes con dolor pélvico crónico y síntomas urinarios se encuentra una alta prevalencia de cistitis intersticial y trigonitis crónica...

Objective: this study was aimed at describing cystoscopy findings in a group of patients suffering from chronic pelvic pain (CPP) who had consulted at a reference clinic in Pereira, Colombia. Materials and methods: a cross-sectional study was made of females who had consulted for CPP at a level 4 hospital and referral center between July 2006 and October 2008 and who had then undergone laparoscopy and cystoscopy. Data was extracted from their clinical histories using a tailor-made form. Interstitial cystitis and chronic trigonitis prevalence were described. Results: 115 females suffering from CPP underwent laparoscopy and cystoscopy under general anesthetic; 59% of the patients had positive cystoscopy findings for interstitial cystitis. Increased urinary frequency, dysuria and nicturia symptoms had a statistically significant correlation with abnormal cystoscopy findings. The main sign found in their physical examination was pain on palpating the bladder. The potassium chloride test had 71% sensitivity and 44% specificity, with 60% positive predictive value (PPV) and 57% negative predictive value (NPV). Conclusions: a high prevalence of interstitial cystitis and chronic trigonitis was found in patients suffering from chronic pelvic pain and urinary symptoms...

Excreção urinária de glicosaminoglicanos em crianças com bexiga neurogênica secundária a mielomeningocele / Urinary excretion of glycosaminoglycans in children with neurogenic bladder secondary to myelomeningocele

A excreção urinária de glicosaminoglicanos (GAG) está alterada em várias patologias do trato urinário; o padrão de excreção pode estar associado com o estado da doença. A excreção urinária de GAG em crianças com bexiga neurogênica (BN) secundária a mielomeningocele (MMC) pode também estar alterada, mas até a presente data não há detalhamento epidemiológico dos pacientes e não se correlacionou o padrão de excreção com grau de disfunção vesical. Analisamos a excreção urinária de um grupo bem definido de crianças de 17 pacientes com MMC, 10 meninos e 7 meninas (média de idade +- DP de 4,6 +- 2,9 anos) foram obtidas durante o exame cistométrico. As amostras do grupo controle foram obtidas de 18 crianças normais, 13 meninos e 5 meninas (6,9 +- 2,2 anos). Todas as crianças não estavam com infecção urinária, tinham função renal normal e não estavam sob tratamento farmacológico. A quantificação do GAG urinário total foi expressa em ug de ácido hexurônico/mg de creatinina e a proporção dos diferentes tipos de GAGs sulfatados foi obtida por eletroforese em gel de agarose. A avaliação cistométrica foi realizada utilizando aparelho de urodinâmica Dynapack modelo MPX816 (Dynamed, São Paulo, Brasil), a partir da qual o escore cistométrico foi calculado de acordo com procedimento recente publicado [14]. Não observamos diferença significativa na excreção urinária de GAG total entre meninos e meninas tanto no grupo com MMC (0,913 +- 0,528 vs 0,867 +- 0,434, p>0,05) como no grupo controle (0,546 +- 0,240 vs 0,699 +- 0,296, p>0,05). Os resultados mostraram também que a excreção de GAG urinário não se correlacionou com a idade tanto no grupo com MMC (r = -0,28, p>0,05) como no grupo controle (r = -0,40, p>0,05). Entretanto, a comparação dos dois grupos mostrou que o grupo com MMC excretava 52% a mais de GAG total que o grupo controle (0,894 +- 0,477 vs 0,588 +- 0,257, p<0,04). Nesses pacientes a excreção de GAG total não se correlacionou com a complacência vesical...

Urinary glycosaminoglycan (GAG) excretion is altered in a number of urinary tract disorders, and the excretion pattern may be associated with disease state and/or outcome. GAG excretion in children with neurogenic bladder secondary to myelomeningocele (MMC) may be affected, but existing data lack more detailed demographics and does not correlate excretion pattern with severity of bladder dysfunction. Here we analyzed GAG excretion in a well defined group of children with MMC and correlated the results with cystometric score. Urine specimens from 17 patients (10 boys, 7 girls) mean age +- SD, 4.6 +- 2.9 years) were obtained during cystometry. Control specimens were from 18 normal children (13 boys, 5 girls) (6.9 +- 2.2 years). All children were free from urinary infection, had normal renal function, and were not under pharmacological treatment. Total urinary GAG was assayed as ug hexuronic acid/mg urinary creatinin e, and sulfated GAGs were determined by agarose gel electrophoresis. Cistometry was done using a Dynapack MPX816 (Dynamed, São Paulo, Brazil), from wich a cystometry score was calculated according to a recent procedure [14]. There were no significant differences in total GAG excretion between male and female individuals in the MMC (0.913 +- 0.528 vs 0.867 +- 0.434, p>0.05) and control (0.546 +- 0.240 vs 0.699+- 0.296, p>0.05) groups. Also, urinary GAG did not correlated with age in the MMC (r = -0.28, p>0.05) and control (r = -0.40, p>0.05) groups. However, MMC patients excreted 52% more GAG than controls (0.894 +- 0.477 vs 0.588 +- 0.257, p<0.04). In these patients, total GAG excretion was not associated with vesical complicance alone (r = -0.18, p>0.05), but was significantly and negatively correlated (r = -0.56, p<0.05) with cystometric score. On average, MMC patients with worst scores (<9) excreted 81% more GAG than those with better scores (>9) (1.157 +- 0.467 vs 0.639 +- 0.133, p<0.04). Chondroitin sulfate prevailed in both groups...

Cistitis intersticial o vejiga dolorosa: Un desafío para el clínico / Interstitial cystitis: A challenge for the clinician

La cistitis intersticial se define como un síndrome clínico caracterizado por un incremento de la frecuencia urinaria, urgencia miccional y/o dolor abdominal o perineal en ausencia de infección urinaria o enfermedad conocida del aparato urinario. Se divide de acuerdo a los hallazgos citoscópicos en ulcerativa o no. La base del diagnóstico es clínica apoyada en scores de probabilidad y pruebas invasivas. Con la comprensión de la fisiopatología se ha desarrollado un abanico de posibilidades terapéuticas. Comunicamos el caso de una paciente sintomática por cuatro años con diagnóstico de cistitis intersticial con úlcera de Hunner por cistoscopia y excelente respuesta a la amitriptilina. Es una enfermedad que produce considerable alteración de la calidad de vida, por lo que es importante que los médicos estén familiarizados con este cuadro.

Interstitial cystitis is characterized by over 6 months of chronic pain, pressure and discomfort felt in the lower pelvis or bladder. It is often relieved with voiding, along with daytime frequency and nocturia in the absence of an urinary tract infection. The disorder can be divided clinically into two groups -ulcerative and non-ulcerative- based on cystoscopic findings and response to treatment. Management follows an approach of applying the least invasive therapy that affords sufficient relief of symptoms. We report a case of a patient with interstitial cystitis. The diagnosis was performed by symptoms and lesion in the cystoscopy and excellent response to amitriptyline.

Urinary proteomics evaluation in interstitial cystitis/painful bladder syndrome: a pilot study

PURPOSE: Interstitial cystitis/painful bladder syndrome (IC/PBS) is characterized by chronic pain, pressure and discomfort felt in the pelvis or bladder. An in-depth shotgun proteomics study was carried out to profile the urinary proteome of women with IC/PBS to identify possible specific proteins and networks associated with IC/PBS. MATERIALS AND METHODS: Urine samples from ten female IC/PBS patients and ten female asymptomatic, healthy control subjects were analyzed in quadruplicate by liquid chromatography-tandem mass spectrometry (LC-MS/MS) on a hybrid linear ion trap-orbitrap mass spectrometer. Gas-phase fractionation (GPF) was used to enhance protein identification. Differences in protein quantity were determined by peptide spectral counting. RESULTS: a-1B-glycoprotein (A1BG) and orosomucoid-1 (ORM1) were detected in all IC/PBS patients, and = 60 percent of these patients had elevated expression of these two proteins compared to control subjects. Transthyretin (TTR) and hemopexin (HPX) were detected in all control individuals, but = 60 percent of the IC/PBS patients had decreased expression levels of these two proteins. Enrichment functional analysis showed cell adhesion and response to stimuli were down-regulated whereas response to inflammation, wounding, and tissue degradation were up-regulated in IC/PBS. Activation of neurophysiological processes in synaptic inhibition, and lack of DNA damage repair may also be key components of IC/PBS. CONCLUSION: There are qualitative and quantitative differences between the urinary proteomes of women with and without IC/PBS. We identified a number of proteins as well as pathways/networks that might contribute to the pathology of IC/PBS or result from perturbations induced by this condition.