Orientador: Edson Antunes / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-25T08:00:03Z (GMT). No. of bitstreams: 1 Ramos-Filho_AntonioCelsoSaragossa_D.pdf: 3024613 bytes, checksum: a03a80c65d863acd441249f461461216 (MD5) Previous issue date: 2014 / Resumo: Os receptores TRPV4 e TRPM8 são expressos no urotélio e em fibras aferentes sensitivas da bexiga. Fisiologicamente, a ativação mecânica do receptor TRPV4 na parede da bexiga participa do controle miccional. Em doenças de origem inflamatória, esses receptores adquirem funcionalidade importante. As disfunções da bexiga no diabetes podem estar associadas a alterações ao nível de detrusor, inervação e urotélio. A disfunção urotelial parece ser a responsável por desencadear as alterações neurais e musculares da bexiga. Assim, o objetivo do presente estudo foi investigar os mecanismos fisiopatológicos da ativação dos receptores TRPV4 e TRPM8 no estado diabético em camundongos. Para tanto, dividimos o estudo em duas etapas, sendo que na primeira avaliamos a participação dos receptores TRPV4 e TRPM8 nos mecanismos contráteis e relaxantes do detrusor isolado de animais controles e knockout para esses canais. Em uma segunda etapa estudamos a ativação desses canais em camundongos diabéticos pela injeção intraperitoneal de estreptozotocina (180 mg/Kg) por 4 semanas. Em fragmentos do detrusor isolados de camundongos mostramos que o agonista do receptor TRPV4, GSK1016790A, causou resposta contrátil dependente da concentração. Por outro lado, quando os tecidos foram contraídos com solução despolarizante de KCl, o GSK1016790A causou relaxamento da preparação. No detrusor isolado de animais TRPV4-/- verificamos hipercontratilidade ao carbacol (agonista muscarínico) e à estimulação elétrica, assim como redução no relaxamento ao agonista ?-adrenérgico não-seletivo, isoprenalina. Estes efeitos não foram obtidos com os antagonistas dos receptores TRPV4, RN1734 e HC067047. A indução do diabetes causou nocicepção mecânica e aumento da proporção entre bexiga e peso corpóreo após 4 semanas da injeção. A avaliação miccional dos animais diabéticos mostrou aumento da capacidade, frequência urinária e das contrações involuntárias da bexiga. Observamos ainda hipercontratilidade do detrusor ao carbacol, à estimulação elétrica e ao KCl. A indução do diabetes em animais TRPV4-/- não modificou as disfunções "in vivo" e "in vitro" observadas nos animais wyld type diabéticos, mostrando que a ausência crônica dos receptores TRPV4 desencadeia alterações miccionais que são anteriores as causadas pelo diabetes. Também verificamos que os animais TRPM8-/- não apresentam alteração na resposta contrátil ao carbacol e à estimulação elétrica. Por outro lado, o mentol, mas não a icilina, reduziu significativamente as respostas contráteis nestes animais. O mentol inibiu o influxo de cálcio extracelular em cultura de células da musculatura lisa da bexiga por mecanismo inibitório direto nos canais Cav1.2. O tratamento agudo com mentol, intraperitoneal e intravesical, atenuou as disfunções miccionais observadas nos camundongos diabéticos. "In vitro" o pré-tratamento com mentol reduziu a hipercontratilidade ao carbacol no grupo diabético, sem alterar a resposta no grupo controle. Concluímos que o mentol impede a resposta contrátil da bexiga por mecanismo independente do receptor TRPM8 bloqueando o influxo de cálcio extracelular nos canais Cav1,2, podendo ser utilizado como tratamento na hiperatividade de bexiga de origem miogênica / Abstract: The TRPV4 and TRPM8 receptors are expressed in bladder urothelium and sensitive afferent fibers. Physiologically, the mechanical activation of TRPV4 receptor in the bladder wall is involved in micturition control. In inflammatory diseases, these receptors may have important roles. The bladder dysfunction in diabetes may be associated with changes at the level of detrusor, innervation and urothelium. The urothelial dysfunction triggers neural changes, modifying consequently the smooth muscle contractility. Thus, the goal of the present study was to investigate the pathophysiological mechanisms of TRPV4 and TRPM8 receptor activation in physiological and diabetic conditions in mice. For this purpose we divided the study in two phases, the first of which we evaluated the participation of TRPV4 and TRPM8 receptors in detrusor contractile and relaxing mechanisms in control and knockout animals for these channels. In the second phase we studied the activation of these channels in diabetic mice induced by intraperitoneal injection of streptozotocin (STZ; 180 mg / kg, 4 weeks). The TRPV4 agonist GSK1016790A produced concentration-dependent detrusor contractions. On the other hand, in detrusor pré-contracted with KCl (80 mM), GSK1016790A caused relaxation responses. In TRPV4-/- animals, we verified hypercontractility to carbachol (muscarinic agonist) and electrical-field stimulation, as well as a decreased relaxation to isoprenaline (non-selective ?-adrenergic agonist). These effects were not obtained with the TRPV4 antagonists, RN1734 and HC067047. Induction of diabetes with STZ caused hyperglycemia, mechanical nocicepton, and increased ratio between bladder and body weight after 4 weeks. The miccturition evaluationin diabetic animals showed increased capacity, urinary frequency, and non-voiding contractions. Hypercontractility to carbachol, electrical-field stimulation and KCl in isolated detrusor were lso observed. The induction of diabetes in TRPV4-/- animals did not change the urinary dysfunctions. Our data are consistent with the proposal that TRPV4 receptor has a physiological function in micturition control by decreasing muscarinic-induced contractions and increasing ?-adrenergic-mediated relaxations. Moreover, the bladder contractions to carbachol and EFS in TRPM8-/- did not significantly change compared to TRPM8+/+. However, menthol (300 ?M), but not icilin (1 ?M), significantly inhibited these contractile responses. The menthol (300 ?M) inhibited extracellular calcium influx in bladder smooth muscle cell culture by direct mechanism though Cav1.2 channels. In addition the acute treatment with menthol, intraperitoneal and intravesical, atenuated the micturition dysfunctions observed in diabetic mice. Also, detrusor preparations pre-treated with menthol decreased carbachol hypercontractility, without changing the responses in normoglycemic group. Menthol reduces bladder contractions by mechanisms independent of TRPM8 receptor activation, inhibiting extracellular calcium influx through Cav1.2 channel, thus been considered as treatment for bladder overactivity of myogenic origin / Doutorado / Farmacologia / Doutor em Farmacologia

Orientador: Elizabeth Maria Aparecida Barasnevicius Quagliato / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-22T20:16:26Z (GMT). No. of bitstreams: 1 Sousa_RaimundoNonatoCampos_D.pdf: 2351873 bytes, checksum: aa05f2a60629deedfa05db1c8ace9d8b (MD5) Previous issue date: 2013 / Resumo: Objetivos: Avaliar em mulheres com doença de Parkinson e disfunções urinárias as correlações dos sintomas urinários com os sintomas motores e disfunções mentais. Verificar a prevalência de hiper-reflexia detrusora (HD), bem como analisar em longo prazo a gravidade do desempenho motor, estadiamento de Hoenh-Yahr, habilidades funcionais, funções neuropsicológicas e a magnitude da progressão desses aspectos clínicos e do declínio cognitivo em pacientes com HD. Sujeitos e Métodos: Estudamos uma coorte ambulatorial de sessenta e três (63) pacientes com DP cujos aspectos neurológicos foram avaliados com a utilização das escalas Unified Parkinson's Disease Rating Scale (UPDRS) e a escala de Hoehn-Yahr. As habilidades funcionais foram avaliadas pela escala Schwab & England e a função urológica foi quantificada pela International Prostatic Symptom Scale (IPSS) e qualificada pelo estudo urodinâmico. Foram então categorizados dois grupos: pacientes com e sem HD. Após sete anos os mesmos parâmetros foram reavaliados e a escala Montreal Cognitive Assessment (MoCA)-versão brasileira foi utilizada para o rastreamento neuropsicológico. Resultados: Na avaliação inicial foi constatada correlação positiva entre os sintomas urinários e a gravidade da doença, porém não havia correlação entre a sintomatologia urinária e os sintomas mentais. Sintomas motores, estágio de gravidade da doença e habilidades funcionais eram mais graves em pacientes com HD. Na reavaliação, os grupos não apresentavam diferença quanto à magnitude da progressão dos sintomas motores, do estadiamento da doença e das inabilidades funcionais. Foi observado no grupo com HD maior declínio cognitivo e uma nítida progressão dos escores mentais com risco aumentado para demência. Conclusão: Hiper-reflexia detrusora é um achado urodinâmico frequente em mulheres com DP e embora esteja associada à pior desempenho motor, estágios de maior gravidade da doença e inabilidades funcionais, não é um fator de maior progressão desses aspectos clínicos. Por outro lado as pacientes com HD tiveram, em longa duração, significante progressão da sintomatologia neuropsicológica.O perfil do declínio cognitivo e o risco para demência necessitam ser confirmados em estudos posteriores / Abstract: Objectives: This long-term study in women with Parkinson's disease (PD) and lower urinary tract dysfunctions aimed to verify the correlation of urinary symptoms with the severity of the disease and mental functions. Verify the prevalence of detrusor hiper-reflexia (DH) and analyze the severity of motor symptoms, Hoehn and Yahr stage, functional abilities and neuropsychological functions, as well as analyze the progression of these clinical aspects and cognitive decline in patients with DH. Subjects and Methods: We studied a cohort of sixty-three (63) PD patients whose neurological aspects were evaluated with the Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn-Yahr scale. Functional abilities were evaluated by Schwab and England scale and the urological function was quantified by International Prostatic Symptom Scale (IPSS) and qualified by urodynamic study. Two groups were then categorized: patients with and without HD. After seven years the same parameters were re-evaluated and the cognitive functions were assessed with the Montreal Cognitive Assessment (MoCA). Results: At baseline a correlation between urinary symptoms and motor dysfunction was verified but no correlation between urinary symptoms and mental symptoms was observed. The severity of motor symptoms, stage of the disease and functional disabilities were significant in patients with DH. In the follow up, the groups were similar in regards to progression of motor symptoms, Hoehn and Yahr stage and functional disabilities. On the other hand, decline in cognitive function and clear progression of mental scores and risk for dementia was observed in the group with DH. Conclusion: Urinary symptoms are correlated with the severity of the Parkinson's disease. Detrusor hyper-reflexia is a frequent urodynamic finding in women with DP and although it is associated with worse motor performance, stage of the disease and functional disabilities, it is not a factor of greater progression of these clinical aspects of the disease. On the other hand, patients with DH had a significant progression of the neuropsychological symptoms and risk of dementia. The profile of cognitive decline and dementia risk need to be confirmed in subsequent prospective studies / Doutorado / Neurologia / Doutor em Ciências Médicas

Le cancer est une maladie multifactorielle définie par un développement rapide de cellules anormales. Les cellules malignes acquièrent des avantages compétitifs qui permettent une croissance et prolifération anormales, grâce à un large spectre de changements génétiques et épigénétiques conduisant à des changements majeurs dans les profils de transcriptome et protéome et ainsi des modifications dans des voies de signalisation, le trafic intracellulaire et le métabolisme. Des nombreuses voies cellulaires ont été étudiées dans le contexte du cancer, y compris la signalisation, la migration, la perte de la polarité cellulaire apico-basale et l'adhésion cellulaire, cependant très peu est connu sur les altérations au niveau des organelles. Cette thèse a comme objectif d'identifier des altérations dans les compartiments intracellulaires et d'étudier leurs corrélations avec la progression du cancer. Dans la culture cellulaire classique, l'étude systématique de l'organisation du positionnement relatif des organelles est difficile en raison des fortes hétérogénéités morphologiques des cellules. Pour contourner ce problème, nous avons utilisé l’innovante technique des micro-patrons combinée à des cartes de densité des organelles. Après une analyse systématique de différentes lignées cellulaires représentant différents grades du cancer de la vessie, nous avons identifié des changements dans le positionnement de plusieurs organelles. Le changement de position le plus important a été observé pour les lysosomes, dont la distribution était plus périphérique dans les cellules représentant des grades plus avancées du cancer de la vessie. Ceci suggère que le positionnement des lysosomes pourrait être potentiellement important dans la progression du cancer. Par conséquent, nous avons cherché à caractériser l'impact de l’altération des lysosomes sur le comportement des cellules transformées. Nous avons constaté que les changements dans le positionnement des lysosomes jouent un rôle dans l'invasion des cellules cancéreuses de la vessie. En effet, le transport antérograde des lysosomes est en corrélation avec l’invasion 3D, contrairement au transport rétrograde qui corrèle avec une diminution de l’invasion cellulaire. Enfin, nous avons étudié les mécanismes moléculaires par lesquels les altérations du lysosome ont un impact sur l'invasion cellulaire. / Cancer is a multifactorial disease defined by a rapid development of abnormal cells. Malignant cells acquire competitive advantages for growth and proliferation through a big spectrum of genetic and epigenetic changes leading to major changes in the transcriptome and proteome profiles and thus to alterations in multiple signaling pathways, intracellular trafficking and metabolism. Although many cellular pathways have been studied in the context of cancer, including signaling, migration, loss of apical-basal cell-polarity and cell adhesion, little is known about cancer-related alterations on the sub-cellular, organelle level. This PhD thesis aimed to identify alterations in intracellular compartments and to study how these changes correlate with cancer progression. In classical culture, the systematic study on the organization and relative positioning of organelles is challenging because of the strong morphological cell-to-cell variations. To overcome this problem, we used innovative micro-patterning technique in combination with quantitative, probabilistic mapping of cell organelles. Using a systematic analysis of different cell lines representing different stages of bladder cancer, we identified several changes in the positioning of organelles. The most striking phenotype was revealed by lysosomes, whose distribution was more peripheral in cells representing higher grades of bladder cancer. This suggested that lysosome positioning could be potentially relevant in cancer progression. Therefore, we aimed to characterize the impact of lysosome alteration on cell behavior in transformed cells. We found that changes in lysosome positioning played a role on bladder cancer cell invasion. Indeed, anterograde transport of lysosomes correlate with 3D invasion behavior, contrary to retrograde transport that correlated with decreased cell invasion. Finally, we studied about the molecular mechanisms by which lysosome alterations impact cell invasion.

Introduction: Les données des analyses génomiques des tumeurs de vessie ont défini des sous-groupes qui présentent une agressivité et une réponse à la chimiothérapie différents. Notre but était d’identifier des marqueurs moléculaires prédictifs de l'évolution tumorale.Matériels et méthodes: Les ADNs de 54 tumeur solides et de 50 échantillons d’ urines de patients avec une tumeur de vessie ont été hybridés sur la puce CGH (Comparative Genomic Hybridization) BCA-oligo. Des TMAs (Tissue Micro Array) de 140 tissus paraffinés de tumeurs primitives et métastatiques, ont été analysés en immunohistochimie pour les marqueurs impliqués dans: stabilité de l’ADN, prolifération cellulaire et définition de sous-groupe basal ou luminal. Des corrélations avec les données cliniques ont été recherchées à tous les niveaux d’analyse.Résultats: Le nombre d'altérations chromosomiques augmentait significativement avec le stade tumoral. La distribution de ces altérations était cohérente entre les ADNs extraits de tissu tumoral et de prélèvements urinaires. Si aucun marqueur immunohistochimique ne permettait de différencier les patients métastatiques ou non, des profils de marquage similaires ont été observés entre tumeurs primitives et métastases. La présence d'emboles tumoraux lymphatiques était prédictive du statut métastatique. Conclusion: l’utilisation dans la pratique clinique de la puce BCA-oligo pour prédire une évolution d'une tumeur de vessie vers un stade ou un grade plus élevé peut être envisagée, et réalisée sur un simple prélèvement urinaire. La recherche systématique d’emboles lymphatiques sur tumeurs primitives peut être utilisée pour prédire une évolution métastatique. / Introduction: Recent data from genomic analysis of bladder tumors have identified subgroups with different aggressiveness patterns and chemotherapy response profiles. The aim of our study was to identify molecular markers that can be used in clinical practice, to predict the evolution of these tumors in order to personalize their management.Materials and Methods: DNAs extracted from 54 solid tumors and 50 urine samples from patients with bladder cancer were hybridized on the BCA-oligo CGH (Comparative Genome Hybridization) chip. TMAs (Tissue Micro Array) from 140 paraffine-embedded tissues of primary and metastatic tumors, were analyzed in immunohistochemistry with antibodies directed against proteins involved in DNA stability, cell proliferation and the definition of basal or luminal subgroup. Correlations with clinical data were sought at all levels of analysis.Results: The number of chromosomal alterations increased significantly with the tumor stage. In addition, the distribution of these alterations was consistent between the DNAs extracted from tumor tissue and those from urinary samples. If no immunohistochemical marker differentiated between metastatic and non-metastatic patients, similar labeling patterns were observed between primary tumors and metastases. Notably, the presence of lymphatic emboli was predictive of metastatic status.Conclusion: The use in clinical practice of the BCA-oligo chip to predict a progression of a bladder tumor to a higher stage or grade may be considered. This analysis is feasible on urine sample. The systematic search for lymphatic emboli on primary tumors can be used in clinical practice to predict a metastatic evolution.

The aim of the thesis " A Physiotherapist's View of Overactive Bladder function in Multiple Sclerosis Patients" and the influence of physiotherapy on the symptoms of the overactive bladder. This thesis deals with exert influence on symptoms of an overactive bladder by physiotherapy. Therapy is based on the fact that guarding reflexes that maintains continence at the level of spine and subcortical (micturition centre in pons) are activated by the contraction of the pelvic floor muscles. Physiotherapy contains pelvic floor muscle training with biofeedback, behavioral training and training of stabilizing function of pelvic floor muscles. Powered by TCPDF (www.tcpdf.org)

L'activation constitutive de FGFR3 par mutation ou translocation est l'un des évènements les plus fréquents dans le cancer de la vessie. Une dérégulation de RAB25,une protéine impliquée dans le processus de recyclage des récepteurs de surface, a été montrée dans différents cancers. Des données du transcriptome des cancers de vessie ont montré que RAB25 est surexprimé dans les tumeurs présentant des altérations de FGFR3. L'objectif de cette thèse a été d'étudier l'implication possible de RAB25, des protéines de la même famille, RAB11A et RAB11B, et leur effecteurs RAB11FIP2 et MYO5B dans 1) la tumorigénèse des tumeurs altérées pour FGFR3 et 2) le trafic et la signalisation de FGFR3. Nos résultats montrent que l'extinction de ces protéines par des siARNs induit une diminution significative de la viabilité cellulaire des cellules exprimant des formes constitutivement activées de FGFR3. Les effets de la déplétion de RAB25 et RAB11 sur le recyclage de FGFR3, sur les voies de signalisation de FGFR3 et sur l'expression des gènes cibles de FGFR3 suggèrent que le recyclage de FGFR3 régulé par RAB25 et RAB11 peut prolonger le signal de FGFR3 et peut fournir une plateforme pour la signalisation de FGFR3. Nous avons également comparé la distribution cellulaire des formes sauvage et muté (S249C) de FGFR3 portant une étiquette GFP dans des cellules HeLa. Les deux formes de FGFR3 se trouvent dans plusieurs compartiments intracellulaires mais FGFR3 muté se localise préférentiellement dans le compartiment de recyclage. Ce projet nous a permis de mieux caractériser la trafic de FGFR3 dans le cancer de la vessie et son lien avec la signalisation et l'activité de FGFR3. / Activation of FGFR3 by point mutation, translocation and overexpression is one of the most frequent events in bladder cancer. The dysfunction of RAB25, a GTPase involved in endocytic recycling of transmembrane receptor, has been shown in many cancers. Gene expression data in bladder cancer indicates that RAB25 expression is significant higher in tumors carrying altered FGFR3. The thesis project aimed to investigate the potential role of RAB25, proteins from the same family (RAB11A and RAB11B) and their effectors RAB11FIP2 and MYO5B in 1) the tumorigenesis of tumors carrying altered FGFR3 and 2) the trafficking and the signaling of FGFR3. Our results demonstrate that depletion of these proteins by siRNA significantly reduces cell viability in cells expressing constitutively activated forms of FGFR3. The effects of RAB25 and RAB11 silencing on FGFR3 trafficking and signaling and the expression of FGFR3 target genes suggest that the RAB11- and RAB25-mediated recycling can sustain the signaling by protecting altered FGFR3 from the degradation pathway, and can provide a platform for FGFR3 signaling We also compared the subcellular distribution of wild type and mutant (S249C) forms of FGFR3. These two forms localize to different compartments including early endosomes, late endosomes and recycling compartments. The S249C FGFR3 mutant preferentially localizes to the endocytic recycling compartment. Our findings shed light to the molecular mechanisms underlying the relationships between the trafficking and signaling of FGFR3 in the context of bladder cancer.

Orientador: Cássio Luis Zanettini Riccetto / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-24T12:04:58Z (GMT). No. of bitstreams: 1 Palma_ThaisFigueiredo_D.pdf: 5188121 bytes, checksum: 3443d8a70ab4644713a51d88beb4d20c (MD5) Previous issue date: 2014 / Resumo: Introdução: A Síndrome da Bexiga Hiperativa (BH) é definida pela ICS (International Continence Society) como urgência urinária, acompanhada ou não por incontinência e frequentemente associada ao aumento da frequência urinária e noctúria. Objetivo: O objetivo do estudo foi verificar a influência da idade, do índice de massa corporal (IMC) e de antecedentes gestacionais nos sintomas de bexiga hiperativa em mulheres no menacme. Pacientes e Métodos: No total foram avaliados os questionários preenchidos por 1052 mulheres com idade entre 20 e 45 anos na região de Campinas. Foi utilizado o questionário ICIQ-OAB, uma ferramenta específica para bexiga hiperativa, em sua versão validada em Português e uma ficha de avaliação para dados demográficos e história médica, incluindo: idade, peso, altura, paridade e via de parto. Resultados: De modo geral, mulheres com idade entre 35 e 45 anos apresentaram escore do ICIQ-OAB significativamente maior do que todos os outros grupos (20 a 22; 23 a 27 e 38 a 34) (p<0.0001). Mulheres multíparas e primíparas apresentaram escore significativamente maior do que as nulíparas (p<0,001); e os sintomas não diferiram de acordo com a via de parto - vaginal ou cesárea (p=0.0074). Não foram encontradas diferenças significativas no escore entre os grupos de IMC (<18,5; 18,8 a 24,9; 25 a 29,9 e ? 30) (p=0,0066). Também foram encontradas diferenças significativas com relação ao incômodo causado pelos sintomas. Mulheres de 35 a 45 anos se sentem mais incomodadas do que os outros grupos com relação á frequência (p<0.0001), noctúria (p=0.0011), urgência (p=0.0015) e incontinência por urgência (p<0.0001). O incômodo causado pelos sintomas não diferiu entre os grupos de mulheres nulíparas, primíparas e multíparas (p=0,9363). As mulheres com IMC entre 25 e 29,9 apresentaram incômodo maior do que aquelas com IMC entre 18,5 e 24,9, com relação à incontinência por urgência (p=0,002). Conclusões: Na população estudada de mulheres no menacme, os sintomas de bexiga hiperativa são encontrados mais frequentemente e causam mais incômodo em mulheres com idade mais avançada, índice de massa corporal mais elevado e com histórico de pelo menos uma gestação / Abstract: Introduction: Overactive Bladder Syndrome (OAB) is defined by the ICS (International Continence Society) as urinary urgency, with or without urgency incontinence and frequently associated with increase of frequency and nocturia. Objectives: The aim of the study was to verify the influence of age, body mass index (BMI) and obstetric history in the symptoms of overactive bladder in premenopausal women. Patients and Methods: We analyzed a total of 1052 questionnaires that were filled out by women aged 20-45 in the area of Campinas, SP. We chose the ICIQ-OAB questionnaire, a tool that is specific for overactive bladder, in its Portuguese validated version and na assessment form with demographics and medical history, that included: age, weight, height, parity and mode of delivery (vaginal or cesarean). Results: Overall, women aged 35-45 presented higher scores than all other age groups (20 - 22; 23 - 27 and 38 - 34) (p<0.0001). Multiparous and primiparous women presented higher scores than nulliparous ones (p<0,001); and the symptoms did not differ according to mode of delivery ¿ vaginal or cesarean (p=0.0074). No significant differences were found between the BMI groups - <18,5; 18,8 - 24,9; 25 - 29,9 and ? 30 - (p=0,0066). We also found differences regarding symptom bother. Women aged 35-45 were more bothered than all other groups regarding frequency (p<0.0001), nocturia (p=0.0011), urgency (p=0.0015) and urgency incontinence (p<0.0001). Symptom bother did not differ between nuliparous, primiparous and multiparous women (p=0,9363). Women with BMI 25 - 29,9 were more bothered by urgency incontinence than those with BMI 18,5 - 24,9 (p=0,002). Conclusions: In the premenopausal women population of this study, OAB symptoms were found more frequently and cause more bother in older women, with higher BMI and with history of at least one pregnancy / Doutorado / Fisiopatologia Cirúrgica / Doutora em Ciências

Background Waiting times of the fast-track of bladder cancer in Sweden are prolonged compared with set lead times.Aim To investigate if stage and grade of tumor affects waiting times.Method Retrospective single center observational study, Örebro University Hospital, Sweden. All patients who underwent resection of tumor or cystoscopy with biopsy via the fast-track between July 1st 2017 and December 31st 2018 were included, n=119.Result The waiting times of muscle invasive tumors were in general longer than for non-invasive tumors. Referral to TURBT - twelve days (p=0.047), referral to information of diagnosis to patient - seven days (p=0.04) and cystoscopy to TURBT - eleven days (p=0.041.Conclusion MIBC had longer waiting times to most steps of the fast-track. There are conflicting results in previous studies regarding whether extended waiting times result in worse outcomes in those with higher stage and grade of tumors or not. It is known that long waiting times results in higher mortality and psychological stress among the patients why reorganizations at the department should take place.

This thesis is focused on immunochemical determination of concentration of active and inactive form of cathepsin B in patients with bladder cancer in order to compare diagnostic efficiency of methods for their possible use for routine diagnosis. Cathepsin B and procathepsin B were measured in serum and urine in 82 patients with bladder cancer (47 men and 35 women), with the average age of 66.5 year. The control group contain of 72 healthy subjects (31 men and 41 women), with the average age of 58.5 year. The concentration of cathepsin B and procathepsin B in the urine were corrected to creatinine, which was determined by the enzymatic creatinase method. The concentrations of cathepsin B in urine were singnificantly elevated in patients than in control group (median = 3.5 µg/l vs. 0.9 µg/l, P = 0.01), similarly the results of the cathepsin B/creatinine ratio were elevated (median = 0.4 µg/mmol vs. 0.1 µg/mmol, P = 0.01). There were no significant difference in concentration in serum between patients and control group (median = 4.8 µg/l vs. 4.2 µg/l, P = 0.8). The concentration values of procathepsin B were significantly higher in patients compare to control group both in urine (median = 3.9 µg/l vs. 1.4 µg/l, P < 0.0001), in serum (median = 73.3 µg/l vs. 58.7 µg/l, P = 0.0005) and similarly in...

An uncommon case with semi-spheric perivesical calcification after pelvic radiotherapy is reported and the possible pathogenesis of this phenomenon is discussed. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.