Effectiveness of intravesical ozone in interstitial cystitis by the O'Leary-Sant symptom index.

INTRODUCTION AND HYPOTHESIS: A prospective clinical, preliminary study was performed in patients with interstitial cystitis/bladder pain syndrome (IC/BPS) who were nonresponders to conventional treatment and received intravesical ozone as a therapeutic alternative. METHODS: Sixteen patients received six applications of intravesical ozone at a concentration of 41 µg/mL. We evaluated therapeutic efficacy by the percentage reduction of Interstitial Cystitis Symptom and Problem Index scores (ICSI/ICPI-the O'Leary-Sant symptom index), recurrence rate, nonresponse, and side effects in scores collected on admission (pre-treatment), at the end of the therapeutic protocol (post-treatment), and 180 days (follow-up) after the last ozone application. RESULTS: The mean age of women was 52.9 years (SD: 15.5), and the duration of symptoms was 5.7 years (SD: 7.1). The median ICSI on admission was 17 (IQR: 14.25-19.5) and at follow-up was 0.5 (IQR: 0-2), with a reduction of 97.5% (CI: 85.7-100). The median ICSI/ICPI on admission was 31.5 (IQR: 29-35.2) and at follow-up was 2.0 (IQR: 0-3.75), with a reduction of 92.3% (CI: 88.8-100). The recurrence rate was only 6.25%, and no patients were nonresponders to the treatment. CONCLUSIONS: The application of intravesical ozone was effective in the treatment of patients with IC/BPS who were nonresponders to conventional therapy, showing a progressive and safe effect, at least in the short term.

Deletion or pharmacological blockade of TLR4 confers protection against cyclophosphamide-induced mouse cystitis.

Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a chronic inflammatory disease without consistently effective treatment. We investigate the role of toll-like receptor 4 (TLR4) on voiding dysfunction and inflammation in the cyclophosphamide (CYP)-induced mouse cystitis. Male C57BL/6 [wild-type, (WT)] and/or TLR4 knockout (TLR4-/-) mice were treated with an injection of CYP (300 mg/kg, 24 h) or saline (10 ml/kg). The pharmacological blockade of the TLR4 by resatorvid (10 mg/kg) was also performed 1 h prior CYP-injection in WT mice. Urodynamic profiles were assessed by voiding stain on filter paper and filling cystometry. Contractile responses to carbachol were measured in isolated bladders. In CYP-exposed WT mice, mRNA for TLR4, myeloid differentiation primary response 88, and TIR-domain-containing adapter-inducing interferon-ß increased by 45%, 72%, and 38%, respectively ( P < 0.05). In free-moving mice, CYP-exposed mice exhibited a higher number of urinary spots and smaller urinary volumes. Increases of micturition frequency and nonvoiding contractions, concomitant with decreases of intercontraction intervals and capacity, were observed in the filling cystometry of WT mice ( P < 0.05). Carbachol-induced bladder contractions were significantly reduced in the CYP group, which was paralleled by reduced mRNA for M2 and M3 muscarinic receptors. These functional and molecular alterations induced by CYP were prevented in TLR4-/- and resatorvid-treated mice. Additionally, the increased levels of inflammatory markers induced by CYP exposure, myeloperoxidase activity, interleukin-6, and tumor necrosis factor-alpha were significantly reduced by resatorvid treatment. Our findings reveal a central role for the TLR4 signaling pathway in initiating CYP-induced bladder dysfunction and inflammation and thus emphasize that TLR4 receptor blockade may have clinical value for IC/BPS treatment.

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.

Activation of soluble guanylyl cyclase by BAY 58-2667 improves bladder function in cyclophosphamide-induced cystitis in mice.

Activators of soluble guanylyl cyclase (sGC) interact directly with its prosthetic heme group, enhancing the enzyme responsiveness in pathological conditions. This study aimed to evaluate the effects of the sGC activator BAY 58-2667 on voiding dysfunction, protein expressions of α1 and ß1 sGC subunits and cGMP levels in the bladder tissues after cyclophosphamide (CYP) exposure. Female C57BL/6 mice (20-25 g) were injected with CYP (300 mg/kg ip) to induce cystitis. Mice were pretreated or not with BAY 58-2667 (1 mg/kg, gavage), given 1 h before CYP injection. The micturition patterns and in vitro bladder contractions were evaluated at 24 h. In freely moving mice, the CYP injection produced reduced the micturition volume and increased the number of urine spots. Cystometric recordings in CYP-injected mice revealed significant increases in basal pressure, voiding frequency, and nonvoiding contractions (NVCs), along with decreases in bladder capacity, intercontraction interval, and compliance. BAY 58-2667 significantly prevented the micturition alterations observed in both freely moving mice and cystometry and normalized the reduced in vitro carbachol-induced contractions in the CYP group. Reduced protein expressions of α1 and ß1 sGC subunits and of cGMP levels were observed in the CYP group, all of which were prevented by BAY 58-2667. CYP exposure significantly increased reactive-oxygen species (ROS) generation in both detrusor and urothelium, and this was normalized by BAY 58-2667. The increased myeloperoxidase and cyclooxygenase-2 activities in the bladders of the CYP group remained unchanged by BAY 58-2667. Activators of sGC may constitute a novel and promising therapeutic approach for management of interstitial cystitis.

Treatment of bladder pain syndrome and interstitial cystitis: a systematic review.

INTRODUCTION AND HYPOTHESIS: Bladder pain syndrome/interstitial cystitis (BPS/IC) has various treatments; however, no standardized treatment has been established. The aim was to analyze different types of treatment of BPS/IC and their effectiveness. METHODS: A literature review with a search strategy for articles related to BPS/IC published between 1990 and 2014 was conducted on MEDLINE, PUBMED, and SCOPUS. Only randomized controlled trials in women were included in the meta-analysis, while other experimental studies were used as bases for a systematic review of the topic. Clinical trial quality was defined according to the Jadad scale. RESULTS: Of 356 articles, 13 were included in the analysis. The intervention methods were as follows: instillation of hyaluronic acid, botulinum toxin A, intravesical lidocaine, hyperbaric chamber, massage, physiotherapy, phosphate-buffered saline, piroxicam in combination with doxepin, and others. We did not find any treatment with at least two randomized controlled trials for meta-analysis. Among the assessment tools for symptoms of BPS/IC, the most frequently used were the visual analogue scale, voiding record, and the O'Leary-Sant questionnaire. CONCLUSION: Existing studies were not able to define the best approach for the treatment of BPS/IC. The lack of standardized treatment may be related to the diversity of interventions used; therefore, further studies with better methodological quality are needed.

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.