Derivados de Xanten-9-Ona : Síntese, determinação estrutural e avaliação de actividades biológicas

Dissertação de Doutoramento em Química Farmacêutica apresentada à Faculdade de Farmácia da Universidade do PortoEsta dissertação inclui a síntese e a determinação estrutural de doze xantonas oxigenadas simples e de cinco xantonolignóides, bem como a avaliação das respectivas actividades biológicas, inibição do crescimento de linhas celulares tumorais humanas e inibição da proliferação de linfócitos humanos in vitro, e modulação da quinase C de proteínas. É descrito o planeamento e a síntese baseada em processos biomiméticos de cinco xantonolignóides: a trans-(±)-kielcorina C, a cis-(±)-kielcorina C* , a trans-(±)-kielcorina D* , a trans-(±)-isokielcorina D* e a trans-(±)-kielcorina E*. A metodologia de síntese baseou-se na reacção de acoplamento oxidativo de orto-di-hidroxixantonas com o álcool coniferílico na presença de um agente oxidante. A estereoquímica e a regioquímica do processo de síntese foi analisada por comparação de vários agentes oxidantes e por estudos computacionais. Foi desenvolvido um método de HPLC para a separação e quantificação dos derivados kielcorínicos. Foi efectuada a resolução analítica dos cinco pares de enantiómeros kielcorínicos, por HPLC, em diferentes fases estacionárias quirais. A coluna de tris-3,5-dimetilfenilcarbamato de amilose foi a escolhida para a resolução semi-preparativa das misturas racémicas trans-(±)-kielcorina C, trans-(±)-kielcorina D*, trans-(±)-isokielcorina D* e trans-(±)-kielcorina E*. Foram sintetizadas as seguintes xantonas simples oxigenadas: 1-metoxi-, 1-hidroxi-, 2-metoxi-, 2-hidroxi-, 3-metoxi-, 3-hidroxi-, 1,2-dimetoxi-, 1,2-di-hidroxi-, 2,3-dimetoxi-, 2,3-di-hidroxi-, 3,4-dimetoxi- e 3,4-di-hidroxixantona. A metodologia de síntese destes compostos foi baseada na formação de intermediários ciclizáveis, do tipo benzofenona ou éter bifenílico, ou na reacção de Grover, Shah e Shah. Um novo método de síntese é descrito para xantonas 1,2-di-oxigenadas.As estruturas dos derivados xantónicos e dos intermediários de síntese foram todas estabelecidas com base em métodos espectroscópicos (IV, UV, RMN de 1H e 13C, COSY, HETC ..

Transcriptional profiles of the human pathogenic fungus paracoccidioides brasiliensis in mycelium and yeast cells

This work was supported by MCT, CNPq, CAPES, FUB, UFG, and FUNDECT-MS. PbGenome Network: Alda Maria T. Ferreira, Alessandra Dantas, Alessandra J. Baptista, Alexandre M. Bailão, Ana Lídia Bonato, André C. Amaral, Bruno S. Daher, Camila M. Silva, Christiane S. Costa, Clayton L. Borges, Cléber O. Soares, Cristina M. Junta, Daniel A. S. Anjos, Edans F. O. Sandes, Eduardo A. Donadi, Elza T. Sakamoto-Hojo, Flábio R. Araújo, Flávia C. Albuquerque, Gina C. Oliveira, João Ricardo M. Almeida, Juliana C. Oliveira, Kláudia G. Jorge, Larissa Fernandes, Lorena S. Derengowski, Luís Artur M. Bataus, Marcus A. M. Araújo, Marcus K. Inoue, Marlene T. De-Souza, Mauro F. Almeida, Nádia S. Parachin, Nadya S. Castro, Odair P. Martins, Patrícia L. N. Costa, Paula Sandrin-Garcia, Renata B. A. Soares, Stephano S. Mello, and Viviane C. B. ReisParacoccidioides brasiliensis is the causative agent of paracoccidioidomycosis, a disease that affects 10 million individuals in Latin America. This report depicts the results of the analysis of 6,022 assembled groups from mycelium and yeast phase expressed sequence tags, covering about 80% of the estimated genome of this dimorphic, thermo-regulated fungus. The data provide a comprehensive view of the fungal metabolism, including overexpressed transcripts, stage-specific genes, and also those that are up- or down-regulated as assessed by in silico electronic subtraction and cDNA microarrays. Also, a significant differential expression pattern in mycelium and yeast cells was detected, which was confirmed by Northern blot analysis, providing insights into differential metabolic adaptations. The overall transcriptome analysis provided information about sequences related to the cell cycle, stress response, drug resistance, and signal transduction pathways of the pathogen. Novel P. brasiliensis genes have been identified, probably corresponding to proteins that should be addressed as virulence factor candidates and potential new drug targets

Eficácia clínica de novos estudos para o tratamento da Dermatite Atópica: uma revisão integrativa

A dermatite atópica (DA) é a doença de pele mais comum dentre as doenças inflamatórias crônicas da pele, acometendo de 10 a 20% das crianças e até 10% dos adultos em países desenvolvidos. O presente estudo de revisão buscou avaliar a eficácia clínica de novos estudos para o tratamento da dermatite atópica, documentados por meio de estudos clínicos e randomizados. Trata-se de uma pesquisa de revisão integrativa realizada por meio da base de dados PubMed, que levou em consideração os seguintes critérios de inclusão: ensaios clínicos e testes controlados e randomizados; artigos publicados no último ano; que possuíam texto completo disponível e que abordassem acerca da terapêutica da dermatite atópica (DA). Ficou constatado que o brepocitinibe tópico se mostrou bem tolerado nos pacientes que possuem DA de grau leve e moderado, da mesma forma que o upadacitinibe, o qual apresenta um perfil de risco-benefício favorável para o  tratamento da DA moderada e grave em adolescentes. Além disso, o abrocitinibe também demonstrou resultados eficazes, com melhora da qualidade de vida e da coceira noturna em pacientes com DA. Verificou-se, ainda, que os anticorpos neutralizantes de IL-13 apresentam eficácia clínica comprovada em pacientes com DA, em especial quando associados aos costicosteroides tópicos. Essa associação com o traloquinumabe trouxe melhorias de sintomas, com redução de interferência no sono relacionado ao eczema, resultados semelhantes de eficácia quando os corticosteroides são associados ao lebrikizumabe

Congenital malformations in neonates: analysis of morbidity and associated factors

Objective: To evaluate the neonatal morbidity due to congenital malformations in the city of Petrolina-PE, from 2008 to 2013. Methods: A descriptive study with data from the Information System on Live Births (Sinasc). The analyzes were carried out through frequency distribution and measures of central tendency and dispersion. The associations were tested by the Pearson and Kruskal Wallis chi-square tests. Significance was set at 5% and 95% confidence. Results: 436 cases of congenital malformations were recorded in the study period, with 2011 being the highest occurrence year. The mothers of the newborns were young (25.2 years old), single, upper level of education and household. In general multiparous, with single gestation, vaginal delivery and performed up to six prenatal visits. The newborns were males, at 39 weeks or more of gestation and with normal weight (> = 2500g). The malformations of the musculoskeletal system were the most frequent followed by the genitourinary system. Congenital malformations were especially associated with neonatal characteristics such as gender and weight. In all causes the mean weight was greater than 2500g (p <0.05). The causes of malformation of greater occurrence in both sexes were osteomuscular (p <0.05). The aspects of the mother did not present significant differences in the present study (p> 0.05). Conclusion: The present study evidenced relevant aspects in the occurrence of morbidities due to congenital malformations, directing to a greater attention the occurrence of these diseases especially in relation to the newborn

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost