Thesis (doctoral)--Katholieke Universiteit te Nijmegen.

La prostatitis crónica bacteriana y abacteriana es una patología difícil de curar, por la baja penetración de los antibióticos al estroma glandular prostático, por la barrera hematoprostática que está relacionada al gradiente de solubilidad del pH plasmático, liposolubilidad, ionización y enlaces proteínicos. De eso resulta que no existe el antibiótico ideal. (4) El estudio donde se realizó el presente trabajo fue en el Servicio de Urología del Hospital Nacional Hipólito Unanue, donde la prostatitis crónica es una de las patologías más frecuentes en la población de adultos jóvenes del distrito del Agustino. Como se sabe es una patología que altera la calidad de vida del paciente y que frecuentemente no evidencia una mejoría real a pesar del largo tratamiento instaurado ocasionando además gasto económico. En el presente trabajo se consideró analizar los pacientes tratados con antibióticoterapia por 3 a 6 meses, o con otros fármacos, sin evidenciar mejoría. Por otro lado, la vía transuretral para el tratamiento de prostatitis crónica bacteriana y abacteriana.(15) se utiliza para la inyección intraprostatica de antibióticos ,habiendo utilizado en estudio anteriores trimetropim-sulfametoxazol , pero teniendo el inconveniente de los altos costos y no accesibilidad en nuestro medio de la aguja que se incorpora al Cistoscopio para poder punzar la próstata a través de esta vía (34). Teniendo en cuenta todo lo mencionado anteriormente; el presente estudio tiene por finalidad evaluar la eficacia del tratamiento de la prostatitis crónica con inyección intraprostática transperineal mediante una sola aplicación de Cloranfenicol más Dexametasona,constituyendo el objetivo del trabajo . Ya que esta patología amerita un tratamiento para la cura en una sola sesión, evita la pérdida de recursos en los largos tratamientos que ésta demanda, disminuyendo costos económicos y haciendo más asequible a gran número de pacientes. Con la realización del presente estudio, y con los resultados obtenidos, se dará una solución viable a esta patología; ya que al utilizar la mezcla de antibiótico y corticoides según las evidencias se observa que, como potentes antiinflamatorios, mejoran la difusión del antibiótico en la próstata, ya que disminuye la inflamación. También se ha observado que la inflamación produce estrés oxidativo, con aumento de prostaglandinas E2 que inhiben la actividad de las endorfinas beta, que se cree interviene de manera importante para explicar el clásico dolor abdominal bajo, perineal o al eyacular de este tipo de pacientes.(2) Al realizarse por vía transperineal, logramos que el antibiótico y el esteroide ingresen en el tejido prostático; lográndose asì la eficacia de este manejo por el fácil acceso, por la fácil ejecución, bajos costos, lo que lo haría reproducible y asequible en cualquier hospital de nuestro país, creando así una cura accesible para esta patología, en beneficio de nuestros pacientes a quienes nos debemos.

Inaug.-diss.-Bern. / "Literatur-verzeichnis" : p. 31.

No description available.

Excerpt: Chronic prostatitis is relatively common, with a lifetime prevalence of 1.8% to 8.2%.

In summary, the present findings have demonstrated the important roles of CFTR in prostatitis and cancer development, which may provide new insight into the understanding of the prostate in health and disease. The present findings may also have potential application in diagnosis and prognosis of cancer. / In the first part of the study, the possible role and a bacterial killing mechanism involving CFTR-mediated bicarbonate secretion in prostatitis were investigated in a rat prostate model. CFTR was found to be expressed in the epithelium of rat ventral prostate. Experiments using cultured rat primary prostate epithelial cells demonstrated that CFTR was involved in mediating bicarbonate extrusion across the prostate epithelium. The expression of CFTR and carbonic anhydrase II (CAII), a key enzyme involved in cellular HCO 3- production, along with several pro-inflammatory cytokines including IL-6, IL-1beta, TNF-alpha, was significantly up-regulated in the primary culture of rat prostate epithelial cells upon E.coli-LPS challenge. Inhibition of CFTR function in vitro or in vivo resulted in reduced bacterial killing by prostate epithelial cells or the prostate. High HCO3- content (>50mM), rather than alkaline pH, was found to be responsible for bacterial killing. The direct action of HCO 3- on bacterial killing was confirmed by its ability to suppress bacterial initiation factors in E coli. The relevance of the CFTR-mediated HCO3- secretion in human was demonstrated by the upregulated expression of CFTR and CAII in human prostatitis tissues. The present results have demonstrated that CFTR plays a previously undefined role in prostatitis and could be up-regulated during the inflammation in prostate as a host defense mechanism to increase bicarbonate secretion for bacterial killing. / In the second part of the study, the possible role of CFTR in prostate cancer development and the underlying mechanisms were investigated. Our results showed that the expression of CFTR and CAII in prostate was remarkably decreased in aged rat prostate. We observed that testosterone could up-regulate the expression of CFTR and CAII in vitro and in vivo , indicating that the declined male hormones during aging may be responsible for the observed age-dependent expression of CFTR. In the present study, we found that inhibition of CFTR enhanced cell proliferation/anti-apoptosis in the prostate primary epithelial cells. CFTR was detected in all examined prostate cell lines, but with relatively higher expression levels in immortalized cell lines (PZ-HPV-7, PNT1A, PNT2C2) than in cancer cell lines (PC-3, DU-145, LNCaP). Immunohistological studies showed that the expression of CFTR was dramatically reduced in prostate cancer specimens as compared to that in normal prostate tissues. Furthermore, our gain and loss of function studies showed that knockdown of CFTR profoundly enhanced cell proliferation, cell adhesion, invasion and migration, while inhibited apoptosis in prostate cancer cell lines, overexpression of CFTR dramatically suppressed tumorigenic phenotype of cancer cells. Soft agar anchorage-independent growth assay showed that knockdown of CFTR in prostate cancer cells increased the number of colonies formed in soft agar. More importantly, we demonstrated that CFTR knockdown promoted the tumor growth in vivo and forced overexpression of CFTR in prostate cancer cells and ultrasound-mediated gene transfer of CFTR inhibited xenograft tumor growth in vivo. Mechanistically, multiple mechanisms were identified to contribute to the CFTR- mediated tumor suppressive effects. Firstly, CFTR chloride channel function was implicated in the regulation of apoptosis in prostate cancer cells. Secondly, CFTR up-regulated the transcription level of miR-34a and miR-193b, both of which have been indicated as tumor suppressors in multiple cancers. Thirdly, 11 cancer-related genes were found to be up- or down-regulated by CFTR using PCR-array. These data demonstrated that CFTR may play an important role in prostate cancer development by acting as a tumor suppressor. / The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel conducting both Cl- and HCO3 -. It is expressed in epithelial cells of a wide variety of tissues. CFTR is also known to be expressed in human prostate; however, the physiological role of CFTR in the prostate and related diseases remains largely unknown. This thesis explored the biological roles of CFTR in prostatitis and cancer development. / Xie, Chen. / Adviser: Chan LiShaw Chang. / Source: Dissertation Abstracts International, Volume: 73-02, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 175-192). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [201-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2016-07-14T12:01:58Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Tese_Fabiana corrigida.pdf: 10988390 bytes, checksum: 0f7ed97ccd1c58e803213e43db1e6a2c (MD5) / Made available in DSpace on 2016-07-14T12:01:58Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Tese_Fabiana corrigida.pdf: 10988390 bytes, checksum: 0f7ed97ccd1c58e803213e43db1e6a2c (MD5) Previous issue date: 2015-07-29 / FACEPE / O Sildenafil é um inibidor potente e seletivo da fosfodiesterase-5 (PDE5). Este fármaco foi aprovado para uso terapêutico na disfunção erétil e, atualmente, vem sendo usado também no tratamento da hipertensão pulmonar. Embora mantenha um excelente nível de segurança e perfil de tolerabilidade, poucos estudos avaliaram os possíveis efeitos colaterais do tratamento crônico com Sildenafil sobre o sistema reprodutor masculino, especialmente na próstata visando o relaxamento da uretra e alívio dos Sintomas do Trato Urinário Inferior (STUI). Desta forma, avaliamos o efeito do tratamento, em camundongos C57Bl/6, através de análise morfológica, ultraestrutural e expressão molecular de guanilato ciclase solúvel-sGC, Óxido nítrico sintase endotelial-eNOS, Antígeno prostático específico-PSA e Fator de crescimento transformador beta-TGF- no tecido prostático. Foi-se observado que o tratamento com Sildenafil não induz danos evidentes na próstata. Além disso, tem sido demonstrado que Sildenafil tem eficácia terapêutica em doenças inflamatórias crônicas, podendo apresentar uma eficácia terapêutica potencial em diferentes doenças. Entre elas, uma atenção especial tem sido dada para as patologias relacionadas ao trato urogenital masculino, como a Hiperplasia Prostática Benigna (HPB), Câncer de próstata e Prostatites. A inflamação tem sido considerada como um fator etiológio da HPB e STUI. Assim, foi proposto um modelo de lesão prostática com injeção intrauretral de LPS (1mg/ml), em camundongos machos Swiss e C57Bl/6, desenvolvido durante 3, 7, 10 e 14 dias. A análise dos resultados mostrou que a indução intrauretral com lipopolisacarideo-LPS atua como importante agente da HPB, além de promover o aumento de fatores de crescimento (FGF-7 e FGF- β), α-actina e citocinas pró-inflamatórias (IL-1, IL-6, IL-17), tanto no estroma como no epitélio. Uma vez que o Sildenafil tem potencial anti-inflamatório, este estudo se propôs a analisar a ação do Sildenafil em um modelo de lesão prostática experimental, induzido por injeção intrauretral de LPS em camundongos C57BL/6. O tratamento com Sildenafil (25mg/kg) dos animais com prostatite apresentaram redução significativa de -actina, COX-2, NFK- B, IL-6, IL-17 e FGF-7. Por não induzir danos na próstata , o Sildenafil, por não induzir a longo prazo danos evidentes na próstata pode representar uma estratégia farmacológica para o tratamento de doenças inflamatórias crônicas do trato urogenital. / Sildenafil is a potent and selective inhibitor of phosphodiesterase-5 (PDE5). This drug has been approved for therapeutic use in erectile dysfunction and currently has been also used to treat pulmonary hypertension. While maintaining an excellent level of safety and tolerability profile, few studies have evaluated the possible side effects of chronic treatment with Sildenafil on the male reproductive system, especially in prostate aimed at relaxing the urethra and relief of symptoms of Lower Urinary Tract (LUTS). Therefore, we assessed the treatment effect in C57Bl/6 mice, using morphological analysis, ultrastructural and molecular expression of soluble guanylate cyclase-sGC, endothelial nitric oxide synthase, eNOS, prostate-specific antigen PSA and transforming growth factor beta TGF- in prostate tissue. It is observed that the treatment with sildenafil does not induce apparent damage to the prostate. Furthermore, Sildenafil has been shown to have therapeutic efficacy in chronic inflammatory diseases, which have a potential therapeutic efficacy in various diseases. Among them, special attention has been given to the pathologies related to the male urogenital tract, such as Benign Prostatic Hyperplasia (BPH), prostate cancer and Prostatitis. Inflammation has been considered as a factor etiológio of BPH and LUTS. Thus, it has been proposed a prostatic intraurethral injection injury model of LPS (1mg/ml) in male Swiss mice and C57Bl /6 developed for 3, 7, 10 and 14 days. The results showed that the intraurethral induction with lipopolysaccharide-LPS acts as an important agent of HPB, and to promote the increase of growth factors (FGF-7 and FGF- ), -actin and proinflammatory cytokines (IL- 1, IL-6, IL-17), both in the stroma and the epithelium. Since Sildenafil has potential anti-inflammatory, this study aimed to analyze the action of Sildenafil in an experimental prostate injury model induced by intraurethral injection of LPS in C57Bl/6 mice. Treatment with sildenafil (25 mg/kg) of animals with prostatitis showed a significant reduction of -actin, COX-2 NFK-kB, IL-6, IL-17 and FGF-7. By not induce damage to the prostate, Sildenafil, not to induce long term damage evident in the prostate may represent a pharmacologic strategy for the treatment of chronic inflammatory diseases of the urogenital tract.

Orientadores: Ubirajara Ferreira, Wagner Eduardo Matheus / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-14T02:30:40Z (GMT). No. of bitstreams: 1 Stopiglia_RafaelMamprin_M.pdf: 1039972 bytes, checksum: dbe43d140e3febb1ab34ec6ff75b33be (MD5) Previous issue date: 2009 / Resumo: A prostatite assintomática é definida através da detecção laboratorial do aumento de células inflamatórias em secreções uretrais ou urina após massagem da glândula prostática e também detectada em biópsias. Esta alteração inflamatória é reconhecidamente uma causa de elevação dos níveis do PSA. Devido esta elevação também estar associada ao câncer prostático, desenvolvemos um estudo para avaliar a correlação entre prostatite assintomática com a referida doença maligna. No período de janeiro de 2006 à dezembro de 2007 foram selecionados 200 pacientes com idade variando entre 50 e 75 anos e com PSA maior de 2,5ng/ml e menor de 10ng/ml, para pesquisa de prostatite inflamatória assintomática nessa população. Desses pacientes, 98 (49%) apresentaram diagnóstico de prostatite assintomática inflamatória ou tipo IV através de exames laboratoriais com o teste de Meares-Stamey modificado (1). Em seguida, foram randomizados em 2 grupos: Grupo 1 com 49 pacientes que foram tratados com cloridrato de ciprofloxacin 500mg (antibiótico) 2 vezes ao dia por 4 semanas e grupo 2 com 49 pacientes que usaram placebo da mesma forma. No seguimento, o PSA foi dosado após o tratamento e todos os pacientes foram submetidos à biópsia transrretal da próstata. Foram excluídos do estudo pacientes com idade menor de 50, maior de 75 anos, os que recusaram a biópsia, os que apresentaram PSA maior que 10ng/ml devido à maior incidência de tumor (2) e os pacientes que não aceitaram participar do estudo após a aplicação do termo de consentimento. Como resultados, no grupo 1, dos 49 pacientes que receberam antibiótico, 26 (53,06%) apresentaram diminuição do PSA e desses, 7 (26,9%) foram diagnosticados com câncer de próstata na biópsia. Dos 49 pacientes do grupo 2 que receberam placebo, 29 (59,18%) apresentaram diminuição do PSA, sendo que 9 (31%) tiveram câncer na biópsia. Não houve diferença estatística nos grupos estudados, tanto com relação a diminuição do PSA após o tratamento (53,06% X 59,18%) (p=0,10), quanto a presença de tumor nas biópsias nesses casos (26,9% X 31%) (p=0,06). Embora não demonstrada diferença estatística comparado com placebo, foi observado taxa de 26,9% de câncer de próstata na biópsia dos pacientes que apresentaram diminuição do PSA após uso de antibiótico, os quais provavelmente não seriam diagnosticados. Como conclusão a existência de câncer de próstata em pacientes com prostatite assintomática é aproximadamente um terço, mesmo após a diminuição do PSA com tratamento antibiótico / Abstract: Asymptomatic prostatitis is defined through the laboratorial detention of the increase of inflammatory cells in urethral secretions or piss after massage of the prostate gland and also detected in biopsies. This inflammatory alteration is admittedly a cause of rise of the levels of the PSA. Had this rise also to be associated to the prostate cancer, we develop a study to evaluate the correlation between asymptomatic prostatitis with the related malignant illness. In the period of January of 2006 to the December of 2007, 200 patients with age varying between 50 and 75 years and with PSA bigger of 2,5ng/ml and minor of 10ng/ml had been selected, for research of asymptomatic inflammatory prostatitis in this population. Of these patients, 98 (49%) had presented diagnosis of inflammatory asymptomatic prostatitis or type IV through laboratorial examinations with the test of modified Mears-Stamey (1). After that, they had been randomized in 2 groups: Group 1 with 49 patients who had been dealt with ciprofloxacin cloridrate 500mg (antibiotic) 2 times to the day per 4 weeks and group 2 with 49 patients who had used placebo in the same way. In the pursuing, the PSA was dosed the treatment after and all the patients had been submitted to the trans rectal biopsy of the prostate. They had been excluded from the study patient with lesser age of 50, greater of 75 years, the ones that had refused the biopsy, the ones that had presented bigger PSA that 10ng/ml due to bigger incidence of tumor (2) e the patients whom they had not accepted to after participate of the study the application of the assent term. As results, in group 1, of the 49 patients who had received antibiotic, 26 (53.06%) had presented reduction of the PSA and of these, 7 (26.9%) had been diagnosed with cancer of prostate in the biopsy. Of the 49 patients of group 2 that they had received placebo, 29 (59.18%) had presented reduction of the PSA, being that 9 (31%) had had cancer in the biopsy. It did not have difference statistics in the studied groups, as much with regard to reduction of the PSA after the treatment (53.06% X 59.18%) (p=0,10), how much the presence of tumor in the biopsies in these cases (26.9% X 31%) (p=0,06). Although not demonstrated to difference statistics compared with placebo, tax of 26,9% of cancer of prostate in the biopsy of the patients was observed who had presented reduction of the PSA after antibiotic use, which they would probably not be diagnosed. As conclusion the existence of cancer of prostate in patients with asymptomatic prostatitis is approximately one third, exactly after the reduction of the PSA with antibiotic treatment / Mestrado / Cirurgia / Mestre em Cirurgia

Uropathogenic Escherichia coli is a leading cause of urinary tract infections and bacterial prostatitis, the most common UTI complication in men. The initial stages of a successful infection involve bacterial adhesion to host cells through specialized adhesins. FimH, a protein located at the tip of type 1 pili, plays a crucial role as the main mediator for UPEC binding to bladder cells. While the host partners of FimH in the bladder are well-established, the interactions between FimH and prostate cells remain elusive. Consequently, the overarching goal is to enhance comprehension of the initial steps in prostate infection by investigating the interaction of FimH with prostate proteins. To achieve this, a recombinant FimH was constructed and expressed in an inducible expression vector, and an immunofluorescence staining assay was performed which demonstrated distinctive binding patterns in prostate cells compared to the bladder cell line. A Far Western overlay assay, revealed six distinct protein bands in human prostate cells and two in mouse prostate cells, indicating different potential protein partners. These interactions were examined under native conditions by establishing and optimizing a co-immunoprecipitation assay with cell proteins derived from both human and mouse prostates, with the 5637 cell line serving as a positive control. In summary, this study reveals striking differences between FimH binding to prostate and bladder cells, emphasizing the importance of FimH in adhesion and the need for further exploration of FimH interaction with prostate cells.

No description available.