Dynamic transperineal ultrasound (TPUS) video allows for kinematic analysis of urogenital morphology and mobility, however, measures are often limited to peak displacements of anatomical landmarks and are vulnerable to error incurred by probe rotation during imaging. This thesis aimed to (1) develop an algorithm to calculate kinematic curves of urogenital landmark motion from TPUS video and to (2) investigate the error incurred in these kinematic measures due to in-plane ultrasound probe rotation. UROKIN, a semi-automated software, was developed and, as a proof of concept, was used to identify differences in urogenital kinematics during pelvic floor muscle maximum voluntary contractions between women with and without stress urinary incontinence. A mathematical model revealed that the error incurred by TPUS probe rotation in the x- (anterior-posterior) and y- (cranial-caudal) directions, was a factor of: r, the radius of rotation; Ɵ, the in-plane angular probe rotation; and α, the angular deviation between the anatomical planes and the coordinate system in which error was calculated. As an absolute measure, the error incurred by in-plane probe rotation is reduced to a factor of only r and Ɵ. Moving forward, UROKIN must be adapted to include findings from (1), and must be tested for validity and reliability.

As a result of alcohol consumption being highly prevalent in today’s society, research has been done to investigate the effects of alcohol on the body’s physiological systems. Research has indicated that heavy alcohol consumption is detrimental to the normal structure and function of some organs, especially the liver. However, little research has focused on the effects of chronic alcohol consumption on the female reproductive system. To investigate these effects, the uterine tissues of mice fed an ethanol diet (the NIAAA model also known as the Lieber-DeCarli diet) and mice fed a control diet were compared. The NIAAA model was chosen for this research because it simulates the drinking pattern that is known to cause liver disease in alcoholic hepatitis patients. This is achieved by incorporating both chronic and binge drinking patterns of alcohol consumption. In this study, the mucin layer that lines the endometrial surface of the uterus was analyzed in mice separated into ethanol and control fed groups. The ethanol fed mice were put on the Lieber-DeCarli 5% (v/v) ethanol diet ad libitum for 10-days followed by a single high dose of ethanol (5g/kg) on the 11th day. The control fed mice were placed on an ethanol free isocaloric diet (supplemented with maltose dextrin to match the calories of ethanol). After the 11th day, the mice were sacrificed, and uterine tissues were harvested. The tissues were then embedded in paraffin, sectioned, stained via the Hematoxylin and Eosin (H&E) technique, and examined under a microscope. The thickness of the uterine mucin layer was then measured for each animal and the average thicknesses were calculated. A one-way ANOVA test was employed to compare the mucin thickness between the two groups of animals. The test revealed no statistically significant difference between the thicknesses of the uterine mucin layer in the control and ethanol fed animals (P-value: 0.774).

Bladder cancer is the one of the most common malignancies of the genitourinary system and the overwhelming majority of those cases, approximately 90% in the United States(1), are of the urothelial/transitional cell histologic type. Small cell histologic type of bladder cancer is extremely rare with a mean frequency of 0.7% (1), and due to its rarity, there have not been any large phase III clinical trials in order to establish a definitive treatment regimen. We report here one such case of this rare type of bladder cancer and our approach towards treatment. A 69-year-old man had an incidental finding of microscopic hematuria during routine annual testing performed by his primary care physician. He was referred to a urologist for further evaluation, and in the interim, he began to experience symptoms of nocturia, dysuria and gross hematuria. Cystoscopy revealed a 5 cm sessile mass within the bladder and transurethral resection of the tumor was performed. Histopathological analysis of the tumor revealed muscle invasive poorly differentiated urothelial carcinoma with neuroendocrine features suggestive of small cell carcinoma. Follow-up systemic imaging only revealed multiple lesions in the liver, with the largest solitary liver lesion measuring 4.4 x 3.4 cm and no discrete lung lesions. Patient was started on palliative systemic chemotherapy with carboplatin and etoposide and follow-up imaging demonstrated excellent response after four cycles of treatment; however, follow-up imaging after the completion of 6 cycles of treatment demonstrated disease progression. Patient was referred for consideration of enrollment into any clinical trials; however, unfortunately no trials were found to be available. Patient was subsequently offered systemic treatment with single-agent immunotherapy with pembrolizumab. Due to development of left sided hydronephrosis, nephrostomy tube placement was performed and patient was also started on palliative radiation. Primary small cell carcinoma (SCC) of the bladder is an exceedingly rare malignancy and therefore, data is not readily available in order to guide treatment decisions. The most commonly administered regimen consists of etoposide with a platinum agent, and this regimen is extrapolated from the treatment of SCC of the lung. However, as for patients like ours, who had progression of disease in a short interval and are deemed primary treatment (platinum) refractory, the prognosis certainly becomes far more grim and the treatment choices even more limited. In sharing our treatment approach, we hope to be able to provide insight towards potential future treatment choices for this most-challenging diagnosis, primary small cell carcinoma of the bladder. (1) Blomjous CE, et. al. Small cell carcinoma of the urinary bladder. A clinicopathologic, morphometric, immunohistochemical, and ultrastructural study of 18 cases. Cancer. 1989 Sep 15; 64(6):1347-57.

Melanosis vesicae (or bladder melanosis) is a rare, benign condition referring to the presence of dark pigmented melanin deposits usually within the bladder mucosa. The clinical presentation can be mistaken for primary or metastatic melanoma of the bladder, and thus a histologic assessment is useful for ruling out a malignant diagnosis. All documented cases of melanosis vesicae have presented with urinary symptoms, including hematuria, symptoms of cystitis, incontinence and obstruction. This is a case report presenting a 57-year-old female with complaints of incomplete bladder emptying who met criteria for urinary retention. She underwent in-office cystoscopy and was found to have suspected melanosis vesicae. The diagnosis was later confirmed on pathology following a bladder biopsy. The next phase in care for this patient is planned sacral neuromodulation for treatment of urinary retention. Previous case reports of bladder melanosis have suggested an association with melanin deposition and inflammatory mechanisms and have not demonstrated malignant transformation during follow up. This is, to our knowledge, the first report of documented bladder melanosis in conjunction with urinary retention. Further studies are required to understand the etiology, clinical significance, and clinical correlation of melanosis vesicae with urinary dysfunction.

Orientador: Adriana Orcesi Pedro / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-27T01:25:39Z (GMT). No. of bitstreams: 1 Carmignani_LucioOmar_D.pdf: 1313710 bytes, checksum: e5a2ce3ebfaf92d14e105ee597ca752a (MD5) Previous issue date: 2015 / Resumo: Objetivos: Comparar os efeitos da ingestão diária de um suplemento alimentar à base de isoflavona de soja, terapia hormonal (TH) de baixa dosagem e placebo sobre a qualidade de vida (QV) em mulheres sintomáticas na pós-menopausa e avaliar a correlação entre a melhora dos sintomas da menopausa e a QV de acordo com o tipo de tratamento e comparar os efeitos de cada uma das intervenções sobre o sistema urogenital da mulher na pós-menopausa. Métodos: Ensaio clínico randomizado, duplo-cego e controlado envolvendo 60 mulheres na pós-menopausa, com idade entre 40 e 60 anos. Foram selecionadas e randomizadas em três grupos: um grupo recebeu um suplemento alimentar à base de soja (isoflavona 90mg/dia), outro grupo recebeu terapia hormonal de baixa dose (estradiol 1mg e acetato de noretisterona 0,5mg) e um grupo-controle que recebeu placebo, por um período de 16 semanas. O Menopause Rating Scale (MRS) foi utilizado para avaliar as mudanças nos sintomas climatéricos. A QV foi avaliada através da Versão Abreviada do Instrumento de Avaliação de Qualidade de Vida da Organização Mundial de Saúde (WHOQOL-BREF). Os instrumentos foram aplicados no início e após 16 semanas de tratamento. As queixas urinárias, vaginais e sexuais foram avaliadas através da subescala urogenital do MRS. A avaliação dos efeitos terapêuticos no sistema urogenital foi realizada através da medida do pH vaginal e calculo do valor de maturação vaginal. A espessura endometrial foi mensurada através da ultrassonografia transvaginal. A análise estatística foi realizada usando-se o teste do qui-quadrado, teste exato de Fisher, teste t de Student pareado, teste de Kruskal-Wallis, teste não paramétrico de Kruskal-Wallis e análise de variância (ANOVA). Para a análise intergrupo dos escores do MRS e da QV foi utilizado ANOVA, teste de Kruskal-Wallis e Kruskal-Wallis seguido de Mann-Whitney. Para a análise de correlação usou-se o coeficiente de correlação de Spearman. Para a comparação intergrupo das subescalas urogenitais do MRS utilizou-se o teste não paramétrico de Kruskal-Wallis seguido de Mann-Whitney. Resultados: A média de idade das participantes foi de 52,4 (±3,9) anos com tempo médio desde a menopausa de 4,1 (±3,1) anos. Os escores de QV aumentaram significativamente no domínio físico da QV nas usuárias da TH e em menor escala no grupo da soja (233,1% x 39,7%; p=0,02). Apenas no grupo que utilizou TH houve correlação significativa entre a melhora dos sintomas climatéricos e a melhora nos domínios físico (p=0,01) e psicológico (p=0,01) da QV e na questão da saúde geral (p<0,01). A avaliação do sistema urogenital mostrou que houve melhora da secura vaginal nos grupos da soja e da TH (p=0,04). As queixas sexuais e urinárias não se alteraram ao longo do tratamento. Apenas no grupo que usou TH houve um aumento significativo no índice de maturação vaginal (p<0,01) e uma diminuição no pH vaginal (p<0,01). Não houve mudança na espessura endometrial e os efeitos colaterais foram semelhantes nos três grupos estudados. Conclusões: O uso da terapia hormonal mostrou-se eficaz na melhora nos escores do domínio físico da qualidade de vida, isto também foi observado com o uso da isoflavona em uma escala muito menor, mas superior ao uso do placebo, porém apenas o grupo que utilizou a terapia hormonal apresentou uma correlação significativa entre a melhora dos sintomas climatéricos e a melhora na qualidade de vida. O uso de suplemento alimentar à base de soja contendo isoflavonas mostrou eficácia comparável à da terapia hormonal na melhora do ressecamento vaginal, sem exercer ação estrogênica no trato urogenital, em mulheres na pós-menopausa, e superior ao placebo / Abstract: Objectives: To compare the effects of a soy-based dietary supplement, low-dose hormone therapy (HT) and placebo on climacteric symptoms and on quality of life (QOL) of symptomatic postmenopausal women, and to evaluate the correlation between the improvement in menopausal symptoms and QOL according to treatment type, and also assess the effects of each intervention on the urogenital system in postmenopausal women. Methods: This was a double-blind, randomized and placebo-controlled clinical trial. Sixty healthy postmenopausal women, aged 40-60, were recruited and randomly assigned to three groups: a soy dietary supplement group (isoflavone 90mg/day), a low-dose HT group (estradiol 1mg plus noretisterone acetate 0.5mg) and a placebo group. Menopausal symptoms changes were evaluated through Menopause Rating Scale (MRS). QOL was measured by the abbreviated version of the World Health Organization¿s Quality of Life instrument (WHOQOL-BREF). These instruments were applied at baseline and after 16 weeks of treatment. Urinary, vaginal and sexual complaints were evaluated by using the urogenital subscale of the MRS. Evaluation of therapeutic effects on urogenital system was performed by vaginal pH measurement and maturation value calculation. Transvaginal sonography was performed to evaluate endometrial thickness. Statistical analysis were performed using the chi-square test, Fisher's exact test, paired Student¿s t-test, Kruskal-Wallis test, Kruskal-Wallis nonparametric test, and analysis of variance (ANOVA). For MRS and QOL scores intergroup analysis were used ANOVA, Kruskal-Wallis test, and Kruskal-Wallis followed Mann-Whitney test. Correlation analysis was performed using the Correlation Spearman Coefficient. For Intergroup comparisons related to MRS urogenital subscale, the Kruskal-Wallis nonparametric test was used, followed by the Mann-Whitney test. Results: The mean age of the patients was 52.4 (±3.9) years, with 4.1 (±3.1) years mean time since menopause. QOL scores increased significantly in the physical health domain of QOL in the users of HT and in a much lesser extent in the soy group (233,1% x 39,7%; p=0,02). It was observed that only in the HT group there was a statistically significant correlation between the improvement of symptoms of total MRS and improvement in the QOL physical (p=0.01) and psychological (p=0.01) domains and also on general health assessment (p<0.01). Urogenital system evaluation showed a significantly improvement in vaginal dryness in the soy group and HT group (p=0.04). Urinary and sexual symptoms did not change with treatment in the three groups. After 16 weeks of treatment, there was a significant increase in maturation value only in the HT group (p<0.01). Vaginal pH decreased only in this group (p<0.01). There were no statistically significant differences in endometrial thickness between the three groups and the adverse effects evaluated were similar. Conclusions: Hormone therapy was effective in improving the physical health domain of QOL, it was also observed with the use of isoflavones on a much lesser extent, but superior to placebo. However, only the HT group showed a significant correlation between the improvement of climacteric symptoms and the improvement in QOL. The use of soy-based dietary supplement containing isoflavones showed an efficacy similar to that of HT in improving vaginal dryness, and greater than placebo, without exerting estrogen action on urogenital tract in postmenopausal women / Doutorado / Fisiopatologia Ginecológica / Doutor em Ciências da Saúde

O objetivo deste trabalho foi verificar o possível efeito protetor da L-glutamina e da L-arginina sobre a próstata ventral de ratos quando administradas por gavagem. Procurou-se simular as condições clinicas de pacientes submetidos à radioterapia pélvica tendo como órgão alvo outro órgão pélvico que não a próstata. Foram analisados os efeitos desta irradiação sobre a próstata considerando este órgão como normal. Foram utilizados ratos Wistar divididos em quatro grupos: Controle, animais não submetidos à irradiação (n= 10); Irradiado, submetidos à irradiação abdominal e sem suplementação adicional de aminoácido por 21 dias (n= 10); Irradiado + Lglutamina, submetidos à irradiação abdominal e com suplementação adicional de L- glutamina por 21 dias (n= 10); e Irradiado + L-arginina, submetidos à irradiação abdominal e com suplementação adicional de L- arginina por 21 dias (n= 9). Os grupos foram mantidos em condições padrão de laboratório durante todas as etapas do experimento. Os animais submetidos à irradiação abdominal receberam uma dose única de 1000 cGy no dia 8 da experimentação. A Lglutamina e a L-arginina foram dissolvidas em água destilada e administrada por gavagem através da agulha IC-810. As próstatas foram removidas e processadas para inclusão em parafina. Foram estudados os seguintes parâmetros: estrutura acinar (área dos ácinos e altura do epitélio) e colágeno analisados por métodos morfométricos e peso corporal. O ganho de peso nos grupos suplementados foi significativamente maior se comparado ao grupo irradiado. Houve redução da altura do epitélio no grupo irradiado quando comparado ao controle. A altura do epitélio no grupo suplementado com L-arginina foi significativamente maior do que nos grupos irradiado e suplementado com L-glutamina. Houve diminuição, de aproximadamente 18%, da área dos ácinos no grupo suplementado com L-glutamina. Já no grupo suplementado com Larginina o valor foi similar ao do controle. O efeito da L-glutamina sobre o parênquima prostático foi o de manter proporcionalmente o colágeno, preservando a integridade da matriz extracelular. No grupo suplementado com L-arginina, apesar da discreta redução na distribuição proporcional de colágeno este também manteve índices semelhantes ao do controle. A radiação abdominal promoveu algumas modificações estruturais na próstata ventral de ratos. Essas modificações podem ser parcialmente prevenidas pela suplementação oral com L-glutamina e de L-arginina. / The aim of this study was to investigate the possible protective effect of L-glutamine and Larginine on the rat ventral prostate when administered by gavage. We tried to simulate the clinical conditions of patients undergoing pelvic radiotherapy as with other pelvic organ target organ than the prostate. We analyzed the effects of irradiation on prostate considering this organ as normal. Wistar rats were divided into four groups: Control, animals not exposed to irradiation (n= 10); Irradiated, submitted to abdominal irradiation and without additional amino acid supplementation (n= 10); Irradiated + L-glutamine, submitted abdominal irradiation and additional supplementation with L-glutamine for 21 days (n= 10), and Irradiated + L-arginine, underwent abdominal irradiation and additional supplementation with L-arginine for 21 days (n=9). The groups were kept under standard laboratory conditions during all stages of the experiment. The animals underwent abdominal irradiation received a single dose of 1000 cGy in eight days of trial. L-glutamine and L-arginine were dissolved in distilled water and administered by gavage needle through the IC-810 . The prostates were removed and processed for paraffin embedding. We studied the following parameters: acinar structure (area of acini and epithelial height) and collagen analyzed by morphometric methods and body weight. Weight gain in the supplemented groups was significantly higher compared to the irradiated group. There was a reduction in epithelial height in the irradiated group compared to control. The height of the epithelium in the group supplemented with L-arginine was significantly higher than in irradiated and supplemented with L-glutamine. There was a decrease of approximately 18% of the area of the lobes in the group supplemented with L-glutamine. In the group supplemented with Larginine was similar to the value of control. The effect of L-glutamine on the prostatic parenchyma was to keep the collagen in proportion, preserving the integrity of the extracellular matrix. In the group supplemented with L-arginine, despite a slight reduction in the proportional distribution of this collagen also maintained similar levels to the control. The abdominal radiation caused some structural changes in rat ventral prostate. These modifications can be partially prevented by oral supplementation with L-glutamine and L-arginine.

O objetivo deste trabalho foi verificar o possível efeito protetor da L-glutamina e da L-arginina sobre a próstata ventral de ratos quando administradas por gavagem. Procurou-se simular as condições clinicas de pacientes submetidos à radioterapia pélvica tendo como órgão alvo outro órgão pélvico que não a próstata. Foram analisados os efeitos desta irradiação sobre a próstata considerando este órgão como normal. Foram utilizados ratos Wistar divididos em quatro grupos: Controle, animais não submetidos à irradiação (n= 10); Irradiado, submetidos à irradiação abdominal e sem suplementação adicional de aminoácido por 21 dias (n= 10); Irradiado + Lglutamina, submetidos à irradiação abdominal e com suplementação adicional de L- glutamina por 21 dias (n= 10); e Irradiado + L-arginina, submetidos à irradiação abdominal e com suplementação adicional de L- arginina por 21 dias (n= 9). Os grupos foram mantidos em condições padrão de laboratório durante todas as etapas do experimento. Os animais submetidos à irradiação abdominal receberam uma dose única de 1000 cGy no dia 8 da experimentação. A Lglutamina e a L-arginina foram dissolvidas em água destilada e administrada por gavagem através da agulha IC-810. As próstatas foram removidas e processadas para inclusão em parafina. Foram estudados os seguintes parâmetros: estrutura acinar (área dos ácinos e altura do epitélio) e colágeno analisados por métodos morfométricos e peso corporal. O ganho de peso nos grupos suplementados foi significativamente maior se comparado ao grupo irradiado. Houve redução da altura do epitélio no grupo irradiado quando comparado ao controle. A altura do epitélio no grupo suplementado com L-arginina foi significativamente maior do que nos grupos irradiado e suplementado com L-glutamina. Houve diminuição, de aproximadamente 18%, da área dos ácinos no grupo suplementado com L-glutamina. Já no grupo suplementado com Larginina o valor foi similar ao do controle. O efeito da L-glutamina sobre o parênquima prostático foi o de manter proporcionalmente o colágeno, preservando a integridade da matriz extracelular. No grupo suplementado com L-arginina, apesar da discreta redução na distribuição proporcional de colágeno este também manteve índices semelhantes ao do controle. A radiação abdominal promoveu algumas modificações estruturais na próstata ventral de ratos. Essas modificações podem ser parcialmente prevenidas pela suplementação oral com L-glutamina e de L-arginina. / The aim of this study was to investigate the possible protective effect of L-glutamine and Larginine on the rat ventral prostate when administered by gavage. We tried to simulate the clinical conditions of patients undergoing pelvic radiotherapy as with other pelvic organ target organ than the prostate. We analyzed the effects of irradiation on prostate considering this organ as normal. Wistar rats were divided into four groups: Control, animals not exposed to irradiation (n= 10); Irradiated, submitted to abdominal irradiation and without additional amino acid supplementation (n= 10); Irradiated + L-glutamine, submitted abdominal irradiation and additional supplementation with L-glutamine for 21 days (n= 10), and Irradiated + L-arginine, underwent abdominal irradiation and additional supplementation with L-arginine for 21 days (n=9). The groups were kept under standard laboratory conditions during all stages of the experiment. The animals underwent abdominal irradiation received a single dose of 1000 cGy in eight days of trial. L-glutamine and L-arginine were dissolved in distilled water and administered by gavage needle through the IC-810 . The prostates were removed and processed for paraffin embedding. We studied the following parameters: acinar structure (area of acini and epithelial height) and collagen analyzed by morphometric methods and body weight. Weight gain in the supplemented groups was significantly higher compared to the irradiated group. There was a reduction in epithelial height in the irradiated group compared to control. The height of the epithelium in the group supplemented with L-arginine was significantly higher than in irradiated and supplemented with L-glutamine. There was a decrease of approximately 18% of the area of the lobes in the group supplemented with L-glutamine. In the group supplemented with Larginine was similar to the value of control. The effect of L-glutamine on the prostatic parenchyma was to keep the collagen in proportion, preserving the integrity of the extracellular matrix. In the group supplemented with L-arginine, despite a slight reduction in the proportional distribution of this collagen also maintained similar levels to the control. The abdominal radiation caused some structural changes in rat ventral prostate. These modifications can be partially prevented by oral supplementation with L-glutamine and L-arginine.

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No. of bitstreams: 1 rafaelcarlosmacedodesouza.pdf: 794221 bytes, checksum: 8b8ac9b5287ce98ce0eaf9610f887577 (MD5) Previous issue date: 2017-08-23 / As cirurgias mutiladoras no sistema geniturinário masculino embora apresentem baixa morbidade, geram comprometimento na qualidade de vida daqueles que necessitam destes procedimentos, devido ao caráter mutilante que afeta suas dimensões físicas, sociais, psicológicas e espirituais. Objetivou-se desvelar sentidos do ser homem após uma cirurgia mutiladora no sistema geniturinário. Pesquisa de natureza qualitativa com referencial teórico, filosófico e metodológico fundado na fenomenologia de Martin Heidegger. O cenário foi um Hospital Universitário da Zona da Mata Mineira, com a participação de 13 homens após cirurgia mutiladora no pênis, testículo e próstata. Os depoimentos foram colhidos nos meses de junho a agosto de 2016 por meio de entrevista fenomenológica com as questões norteadoras: como está o seu dia a dia após a cirurgia; como você se sente após a cirurgia e quais os significados desta cirurgia para você no seu dia a dia. Após leitura atentiva foram apreendidas as estruturas essenciais que permitiram a criação das Unidades de Significação: Sentir dor e que melhorou com a cirurgia; Sentir medo e depois perceber que é tudo normal; Entender que é necessário ter cuidado durante o tratamento e fazer acompanhamento; Viver as mudanças na rotina devido à incontinência urinária e redução da força sexual; Sentir constrangimento, guardar segredo e se sentir diferente. A hermenêutica permitiu desvelar os sentidos do ser-aí-homem-após-uma-cirurgia-mutiladora-no-sistema-geniturinario, revelando que inicialmente é estar preso à facticidade de enfrentar uma intervenção cirúrgica, que até então, não foi esperada. No cotidiano o dasein se encontra na maioria das vezes, no modo-de-ser do impessoal, alienado da sua possibilidade de ser-si-mesmo se mostra decadente e revela o modo do pavor e horror da angústia impropria. Mas, que ocupado do tratamento toma para si a responsabilidade de cuidado consigo e revela o modo-de-ser da preocupação assumindo a possibilidade da cura. No modo-de-ser mais próprio do cotidiano, o impessoal, abrem-se para a falação e a curiosidade. Com o sentimento da perda da masculinidade revela o modo do terror e um modo deficiente de ser-aí-com-os-outros. O estudo contribui de maneira singular no que foi ratificado a partir dos depoimentos: sofrer uma mutilação parcial ou total de um órgão que possui inúmeros significados para o homem e que implica diretamente em sua masculinidade é prejudicial para seu bem-estar. / Mutilation surgeries in the male genitourinary system, although presenting low morbidity, lead to a compromise in the quality of life of those who need these procedures due to the mutilating nature that affects their physical, social, psychological and spiritual dimensions. The objective was to reveal the meanings of being a man after mutilating surgery in the genitourinary system. Research of qualitative nature with theoretical, philosophical and methodological reference founded on the phenomenology of Martin Heidegger. The scenario was a University Hospital of the Zona da Mata Mineira, with the participation of 13 men after mutilating surgery on the penis, testis and prostate. The testimonies were collected in the months of June to August of 2016 through a phenomenological interview with the guiding questions: how is his day to day after the surgery; how you feel after surgery and what the meanings of this surgery are for you in your day to day life. After careful reading, the essential structures that allowed the creation of the Units of Significance were seized: Feeling pain and what has improved with surgery; Feeling scared and then realizing that everything is normal; Understand that care must be taken during treatment and follow-up; To live the changes in the routine due to the urinary incontinence and reduction of the sexual force; Feeling embarrassed, secretive and feeling different. Hermeneutics allowed us to unveil the senses of being-there-man-after-a-surgery-mutilator-in-system-genitourinary, revealing that initially it is being stuck with the facticity of facing a surgical intervention, which until then, was not expected. In everyday life, Dasein finds itself most of the time, in the impersonal way of being, alienated from its possibility of being-itself, decadent and revealing the mode of dread and horror of improper anguish. But, that busy of the treatment takes to itself the responsibility of taking care of with him and reveals the way-of-being of the worry assuming the possibility of the cure. In the way of being more proper of the everyday, the impersonal, open to the talk and the curiosity. With the feeling of loss of masculinity reveals the mode of terror and a poor way of being-with-others. The study contributes in a unique way to what has been ratified from the testimonies: to undergo a partial or total mutilation of an organ that has innumerable meanings for man and that directly implies his masculinity is detrimental to his well-being.

Escherichia coli pode causar infecção intestinal e extra-intestinal, de origem comunitária ou hospitalar, prevalecendo como agente de infecção do trato urinário (ITU). O objetivo do presente estudo foi caracterizar a produção de <font face=\"Symbol\">b-lactamases de espectro estendido (ESBL), grupos filogenéticos, e a relação clonal em isolados clínicos de E. coli recuperados de pacientes ambulatoriais e internados atendidos em um Hospital Universitário de São Paulo, no período de 2005 a 2007. Seis por cento (34/562) dos isolados de E. coli estudados foram caracterizados como produtores de ESBL, sendo associados exclusivamente a infecções extra-intestinais, tanto nos pacientes ambulatoriais (10/28, 36%) como nos internados (18/28, 64%), dos quais 56% (19/34) foram recuperados de uroculturas. Os isolados produtores de ESBL exibiram um fenótipo multirresistente apresentando um perfil de resistência a ampicilina (100%), cefalotina (100%), cefotaxima (100%), ceftazidima (79%), sulfametoxazol-trimetoprim (62%), gentamicina (56%), ciprofloxacina (50%) e amicacina (6%) e permanecendo suscetíveis ao imipinem. A produção de ESBL esteve associada com a presença de genes do tipo blaCTX-M-2 (94%, 32/34), blaCTX-M-15 (3%, 01/34) e blaCTX-M-1 (3%, 01/34). Entre os isolados produtores de ESBL, os grupos filogenéticos B1 (53%, 18/34) e A (18%, 6/34), de baixa virulência, foram predominantes sobre os grupos filogenéticos, de alta virulência, B2 (12%, 4/34) e D (18%, 6/34). De fato, os genes de virulência pap, cnf1, sfa, hly, e iuc, associados com adesão, invasão e disseminação, não foram identificados. A tipagem genotípica por PFGE (utilizando a enzima Xbal) com posterior análise em dendrograma, identificou a presença de 31 clusters entre os 34 isolados produtores de ESBL. Em resumo, a alta incidência de isolados clonalmente não relacionados, pertencentes aos grupos filogenéticos A e B1, de baixa virulência, sugere que cepas comensais de E. coli podem adquirir genes de resistência do tipo blaCTX-M por transferência horizontal contribuindo no estabelecimento e no prognóstico de infecções extra-intestinais, principalmente do trato urinário. / Escherichia coli can produce both intestinal and extraintestinal community- or nosocomial-acquired infection, being the main agent of urinary tract infection (UTI). The aim of this study was to characterize the extended-spectrum beta-lactamase (ESBL) production, phylogenetic groups, and clonal relationship among E. coli clinical isolates recovered from inpatients and outpatients admmited at a university hospital in São Paulo. During 2005 to 2007, six percents (34/562) E. coli isolates were characterized as ESBL producers, being associated exclusively to extraintestinal infections in both inpatients (10/28, 36%) and outpatients (18/28, 64%), of which 56% (19/34) were recovered from urine cultures. ESBL-producing E. coli exhibited a multidrug-resistant phenotype with a resistance profile to ampicillin (100%), cephalotin (100%), cefotaxime (100%), ceftazidime (79%), sulphamethoxazole-trimethoprim (62%), gentamicin (56%), ciprofloxacin (50%), and amikacin (6%), and remaining susceptible to imipenem. In this regard, ESBL production was associated with the presence of blaCTX-M-2 (94%, 32/34), blaCTX-M-15 (3%,1/34) and blaCTX-M-1 (94%, 32/34) genes. On the other hand, low-virulence phylogenetic groups B1 (53%, 18/34) and A (18%, 6/34) were predominant over high-virulence phylogenetic groups B2 (12%, 4/34) and D (18%, 6/34), among ESBL-producing E. coli isolates studied. In fact, pap, cnf1, sfa, hly, and iuc virulence genes associated with adhesion, invasion and dissemination were not identified. Finally, genotyping by PFGE (using XbaI restriction) with subsequent cluster analysis (dendrogram) revealed the presence of 31 cluster among 34 ESBL-producing E. coli. In summary, the high prevalence of clonally unrelated ESBL-producing E. coli belonging to low-virulence phylogenetic groups A and B1 suggest that comensal E. coli can acquire blaCTX-M-like resistance genes through horizontal gene tranfer, contributing to the establishment and outcome of extraintestinal infections, mainly in the urinary tract.

The JNK signal transduction pathway mediates a broad, complex biological process in response to inflammatory cytokines and environmental stress. These responses include cell survival and apoptosis, proliferation, tumorigenesis and the immune response. The divergent cellular responses caused by the JNK signal transduction pathway are often regulated by spatial and cell type contexts, as well as the interaction with other cellular processes. The discovery of additional components of the JNK signal transduction pathway are critical to elucidate the stress response mechanisms in cells. This thesis first discusses the cloning and characterization of two novel members of the JNK signal transduction pathway. JIP1 and JMP1 were initially identified from a murine embryo library through a yeast Two-Hybrid screen to identify novel JNK interacting proteins. Full length cDNAs of both genes were cloned and analyzed. JIP1 represents the first member of the JIP group of JNK scaffold proteins which were characterized. The JNK binding domain (JBD) of JIP1 matches the D-domain consensus of other JNK binding proteins, and it demonstrates JNK binding both in vitro and in vivo. This JNK binding was demonstrated to inhibit JNK signal transduction and over-expression of JIP1 inhibits the JNK mediated pre-B cell transformation by bcr-abl. Over-expressed JIP1 also sequesters JNK in the cytoplasm, which may be a mechanism of the inhibition of JNK signaling. A new, high-resolution digital imaging microscopy technique using deconvolution demonstrated the absence of JNK1 in the nucleus of co-transfected JIP1 and JNK1 cells. The other protein discussed in this thesis is JMP1, a novel JNK binding, microtubule co-localized protein. There is a JBD in the JMP1 carboxyl end and a consensus D-domain within this region. The JMP1 JBD demonstrates an increased association with phospho-JNK from UV irradiated cells compared to un-irradiated cells in vivo. JMP1 also has 12 WD-repeat motifs in its amino terminal end which are required for microtubule co-localization. JMP1 demonstrates a cell cycle specific localization at the mitotic spindle poles. This co-localization is dependent on intact microtubules and the amino-terminal WD-repeats are required for this localization. JMP1 mRNA is highly expressed in testis tissues. Immunocytochemistry on murine testis sections using an affinity purified anti-JMP1 antibody demonstrates JMP1 protein in the lumenal compartment of the seminiferous tubules. JMP1 protein is expressed in primary and secondary spermatocytes, cells which are actively undergoing meiosis. The results obtained from the localization of JMP1 in meiotic spermatocytes led to an investigation of the roles of JNK signal transduction in the testis. The testis is an active region of cellular proliferation, apoptosis and differentiation, which make it an appealing model for studying JNK signal transduction. However, the roles JNK signaling have in the testis are poorly understood. I investigated the reproduction capability of Jnk3-/- male mice and discovered older Jnk3-/- males had a reduced capacity to impregnate females compared to younger animals and age-matched wild type controls. The testis morphology and sperm motility of these animals were similar to wild-type animals, and there was no alteration of apoptosis in the testis. The final section of this thesis involves the study of this breeding defect and investigating for cellular defects that might account for this age-related Jnk3-/- phenotype.