A Brazilian strain of Penicillium verrucosum was cultivated under different conditions in a two-step process, in order to verify the influence of nutrients, and of time periods of pre-fermentative and fermentative steps on the biosynthesis of metabolites. Extracellular and intracellular extracts were obtained from each culture in the four different production media used. Chemical profiles of the extracts were obtained by HPLC. Extract trypanocidal activities against trypomastigote forms of Trypanosoma cruzi were evaluated. The time period of incubation in the pre-fermentative and fermentative media, as well as the different nutrients tested, qualitatively and quantitatively modified the production of secondary metabolites by P. verrucosum, and the extract trypanocidal activities.

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, que me introduziu à Química de Produtos Naturais com ensinamentos de vida e bancada, sendo um exemplo de profissionalismo, amizade e confiança. À Prof. Dra. Suraia Said, pela dedicação à pesquisa e pela disposição em sempre tirar as dúvidas e aconselhar. Ao Prof. Dr. Paulo Cezar Vieira, pelas valiosas contribuições na realização deste trabalho, amizade e pela discussão de vários espectros de RMN. Ao Prof. Dr. Norberto Peporine Lopes, pelas conversas de apoio, amizade e execução dos espectros de massas. Ao Prof. Dr. Fernando Batista da Costa, pelas atenciosas contribuições e divertidas conversas.

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IntroductionThe study aimed to assess long-term outcomes in patients with very high-risk prostate cancer (PCa) – pT3b-T4 N0-1 using the definitive histopathology following radical retropubic prostatectomy (RRP).Material and methodsWe have analyzed 114 patients with very high-risk PCa who underwent RRP between 1995 and 2012. Biochemical and clinical progression-free survival (BPFS, CPFS), cancer-specific and overall survival (CSS, OS) curves were constructed according to the Kaplan-Meier method. Univariate and multivariate Cox regression analysis was utilized to determine predictability of clinical and pathological parameters.ResultsAt the 5 and 10 year mark, the BPFS was 71.3% and 35%, respectively; the CPFS was 86.8% and 69.2%, respectively; the CSS was 98% and 76.3%, respectively and the OS was 90.3% and 62.4%, respectively. Sixteen patients (14%) had lymph-node involvement. Positive surgical margins were present in 64 (56.1%) patients. Neo-adjuvant androgen deprivation therapy (ADT) was received by 22 (19.3%) patients. Adjuvant ADT alone or in combination with external radiotherapy was received by 59 (51.8%) patients. No adjuvant treatment was needed in 29 (25.4%) patients. In univariate and multivariate analysis, neo-adjuvant ADT was associated with an increased risk of BPFS and CPFS.ConclusionsTherapy applied in patients with very high-risk PCa was multimodal in most cases, with RP usually being the first step. The study confirmed that very high-risk PCa is a heterogeneous disease. A significant subset of patients remain without adjuvant therapy treatment.

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