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

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...

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.

An investigation of the nature of bladder mucosal glycoconjugates and their role in interstitial cystitis.

The long-term objective of this study is to elucidate the role of bladder mucosal glycosaminoglycans and mucin glycoproteins in the development of interstitial cystitis and other bladder diseases. Bladder biopsies and urine samples from patients and healthy controls were analyzed for glycoconjugates by biochemical and immunochemical methods. Due to the limited availability of human bladders for research purposes, detailed analysis of rabbit bladders glycoconjugates were also carried out. Biochemical analysis of rabbit bladders indicate that while the major portion of the glycoconjugates in the urothelium is sialoglycoprotein, low levels of heparan sulfate and chondroitin sulfate are also present. The correlating immunohistochemical data show very weak staining of the rabbit bladder epithelium by antiglycosaminoglycan antibodies. In contrast, the lamina propria and muscle layers stained intensely for chondroitin sulfate and hyaluronic acid. Thus, the quantity of glycosaminoglycans associated with the bladder epithelial layer, particularly as extracellular matrix components on the luminal surface of the bladder, appears insignificant. On the other hand, several lectins and anti-epitectin (a MUC1 sialoglycoprotein) antibodies showed strong staining of the luminal surface of rabbit and normal human bladders. Further, preliminary results with anti-epitectin antibodies reveal a weaker and patchy staining of biopsy specimens from interstitial cystitis patients compared to controls. The urinary levels of glycosaminoglycans and epitectin, in interstitial cystitis patients and healthy controls were determined by chemical or immunoassays. Urinary epitectin, but not glycosaminoglycans, was decreased in interstitial cystitis patients.