Impact of exercise training on cancer-induced cardiac dysfunction

Cachexia is a complex syndrome characterized by severe weight loss frequently observed in cancer patients and associated with poor prognosis. Cancer cachexia is also related to modifications in cardiac muscle structure and metabolism leading to cardiac dysfunction. In order to better understand the cardiac remodeling induced by bladder cancer and the impact of exercise training after diagnosis on its regulation, we used an animal model of bladder cancer induced by exposition to N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) in the drinking water. Healthy animals and previously BBN exposed animals were submitted to a training program in a treadmill at a speed of 20m/min, 60 min/day, 5 days/week during 13 weeks. At the end of the protocol, animals exposed to BBN presented a significant decrease of body weight, in comparison with control groups, supporting the presence of cancer cachexia. Morphological analysis of the cardiac muscle sections revealed the presence of fibrosis and a significant decrease of cardiomyocyte’s cross-sectional area, suggesting the occurrence of cardiac dysfunction associated with bladder cancer. These modifications were accompanied by heart metabolic remodeling characterized by a decreased fatty acid oxidation given by diminished levels of ETFDH and of complex II subunit  from the respiratory chain. Exercise training promoted an increment of connexin 43, a protein involved in cardioprotection, and of c-kit, a protein present in cardiac stem cells. These results suggest an improved heart regenerative capacity induced by exercise training. In conclusion, endurance training seems an attractive non-pharmacological therapeutic option for the management of cardiac dysfunction in cancer cachexia.

Identificação de indicadores moleculares de bem-estar durante o cultivo de dourada (Sparus aurata, Linnaeus 1758), utilizando técnicas de proteómica

Dissertação de Mestrado, Biologia Marinha, Especialização em Biotecnologia Marinha, Faculdade de Ciências do Mar e do Ambiente, Universidade do Algarve, 2008

Efeitos a posteriori dos défices hídricos sobre a actividade fotossintética: mecanismos de fotoprotecção e sistema enzimático antioxidante

Tese de dout., Biologia (Fisiologia Vegetal), Faculdade de Engenharia dos Recursos Naturais, Univ. do Algarve, 2005

A proteomic study of the effects of nutrient restriction in utero on postnatal metabolism

It is widely recognized that protein restriction in utero may cause metabolic and endocrine adaptations, which may be of benefit to the neonate on a short-term basis but may cause adverse long-term conditions such as obesity, Type 2 diabetes, metabolic syndrome, hypertension and cardiovascular diseases. Adequate foetal and early post natal nutrient and energy supply is therefore essential for adult animal health, performance and life span. In this project it was investigated the progressive adaptations of the hepatic proteome in male mink offspring exposed to either a low protein (FL) or an adequate protein (FA) diet in utero fed either on a low protein (LP) or on an adequate (AP) diet from weaning until sexual maturity. Specifically, the aim was to determine the metabolic adaptations at selected phases of the animal’s first annual cycle and establish the metabolic priorities occurring during those phases. The three different morphological stages studied during the first year of development included, end of bone growth at 4 months of age, maximal fat accretion at 6 months of age and sexual maturity at 12 months of age. A reference proteome of mink liver coming from these different animal groups were generated using 2D electrophoresis coupled to MALDI-TOF analysis and the way in which dietary treatment affect their proteome was established. Approximately 330 proteins were detected in the mink liver proteome. A total of 27 comparisons were carried out between all different animal groups which resulted in 20 differentially expressed proteins. An extensive survey was conducted towards the characterization of these proteins including their subcellular localization, the biological processes in which they are involved and their molecular functions. This characterization allowed the identification of proteins in various processes including the glycolysis and fatty acid metabolism. The detailed analysis of the different dietary treatment animal groups was indicative of differences in metabolism and also to changes associated with development in mink.

Exploring an uncommon host-parasite interaction to unveil the uniqueness of Perkinsus sp as a model organism

We report the exploration of some unique metabolic pathways in Perkinsus olseni a marine protist parasite, responsible to significant mortalities in mollusks, especially in bivalves all around the world. In Algarve, south of Portugal carpet shell clam Ruditapes decussatus mortalities can reach up to 70%, causing social and economic losses. The objective of studying those unique pathways, is finding new therapeutic strategies capable of controlling/eliminating P. olseni proliferation in clams. In that sense metabolic pathways, were explored, and drugs affecting these cycles were tested for activity. The first step involved the identification of the genes behind those pathways, the reconstitution of the main steps, and molecular characterization of those genes and later on, the identification of possible targets within the genes studied. Metabolic cycles were screened due to the fact of not being present in host or differ in a critical way, such as the following pathways: shikimate, MEP-­‐ isoprenoids, Leloir cycle for chitin production, purine biosynthesis (unique among protists), the de novo synthesis of folates (absent in metazoa) and some unique genes like, the alternative oxidase (a branch of respiratory chain) and the hypoxia sensor HPH. All those pathways were covered and possible chemical inhibition using therapeutic drugs was tested with positive results. The relation between the common host Ruditapes decussatus and P. olseni was also explored in a dimension not possible some years ago. With the accessibility to second generation sequencers and microarray analysis platforms, genes involved in host defense or parasite virulence and resistance to the host were deciphered, allowing aiming to new targets (mechanisms and pathways), offering new possibilities for the control of Perkinsus in close environments. The thousands of genes, generated by this work, sequenced and analyzed from this commercial valuable clam and for Perkinsus olseni will be an important and value tool for the scientific community, allowing a better understanding of host-­‐parasite interactions, promoting the usage of P. olseni as an emerging model for alveolata parasites.

Contamination of farmed gilthead sea bream (Sparus aurata, Linnaeus, 1758) by the parasite Amyloodinium ocellatum: a proteomic approach

Dissertação de mestrado, Aquacultura e Pescas, Faculdade de Ciências e Tecnologia, Uniersidade do Algarve, 2015

Caracterização funcional da microalga extremófila Coccomyxa sp.

Dissertação de mestrado, Biologia Molecular e Microbiana, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2015

Desenvolvimento de um sistema multidimensional para classificação e gestão de informação em saúde: aplicabilidade à informação clínica

Introdução: A profusão de informação na área médica cria problemas de gestão, sendo necessários métodos sistematizados para armazenamento e recuperação. Quando a informação se insere no contexto do processo clínico, os métodos devem integrar terminologias biomédicas controladas e igualmente devem integrar as características desejáveis dirigidas à estrutura, conteúdo e resultados clínicos. O objectivo deste artigo é testar a aplicabilidade e capacidade de recuperação, de um sistema multidimensional desenvolvido para classificação e gestão de informação em saúde. Métodos: A partir das questões recebidas em seis anos (Serviço de Informação de Medicamentos, Serviços Farmacêuticos, Hospitais da Universidade de Coimbra), seleccionaram-se 300 questões sobre informação clínica, por método aleatório informatizado. Caracterizou-se e avaliou-se a aplicabilidade pela quantidade classificada e pela necessidade de alterações ao sistema que é constituído por várias dimensões independentes e que englobam conceitos por vezes hierarquizados. A recuperação das questões foi testada pesquisando informação numa dimensão ou cruzamento de dimensões. Resultados: Todas as questões foram classificadas: 53% são casos clínicos com incidência nas doenças geniturinárias; doenças metabólicas, nutricionais e endócrinas; neoplasias; infecções e doenças do sistema nervoso. Em 81%, o objecto é o medicamento, sobretudo anti-infecciosos e anti-neoplásicos. As áreas de terapêutica e segurança foram as mais solicitadas, incidindo principalmente sobre os assuntos: utilização, reacções adversas, identificação de medicamentos e tecnologia farmacêutica. Na aplicabilidade, foi necessário adicionar alguns conceitos e modificar alguns grupos hierárquicos que não modificaram a estrutura base, nem colidiram com as características desejáveis. As limitações prenderam-se com os sistemas de classificação externos integrados. A pesquisa na dimensão assunto, do conceito administração de medicamentos, recuperou 19 questões. O cruzamento de duas dimensões: anti-infecciosos (externa) e teratogenicidade (assunto), recuperou três questões. Nos dois exemplos recupera-se informação a partir de qualquer um dos níveis da hierarquia, do mais geral ao mais específico e mesmo a partir de dimensões externas. Conclusões: A utilização do sistema nesta amostra demonstrou aplicabilidade na classificação e arquivo de informação clínica, capacidade de recuperação e flexibilidade, sofrendo alterações sem interferir com as características desejáveis. Esta ferramenta permite a recuperação da evidência que interessa orientada para o doente. Introduction: The large amount of information in the medical area creates management problems, being necessary systematic methods for filing and retrieval. With information on the context of clinical records, methods must integrate controlled biomedical terminologies and desirable characteristics oriented to the structure, content and clinical results. The objective is to test the applicability and capacity for retrieval of a multidimensional system developed for classification and management of health information. Methods: Three hundred questions were randomly selected, by computerized method, from the questions received in six years (Medicine Information Service, Pharmaceutical Department, Coimbra University Hospitals). They were characterized and applicability evaluated by classified amount and need to alter the system, which is composed of various independent dimensions, incorporating concepts sometimes hierarchical. Questions retrieval was tested searching information in a dimension or between dimensions. Results: All questions were classified: 53% are clinical cases with illnesses incidence in the genitourinary system; metabolic, nutritional and endocrine disease; cancer; infections and nervous system. In 81%, the object is a drug, mostly anti-infectious and anti-neoplastic agents. The therapeutic and safety areas had been the most requested, regarding the subjects: use, adverse reactions, drug identification and pharmaceutical technology. As to applicability, it was necessary to add some concepts and modify same hierarchical groups, that didn’t modify the basic structure, nor had collided with the desirable characteristics. The limitations were related with the incorporated external classification systems. The search in the subject dimension of the concept drug administration retrieved 19 questions. The search between two dimensions: antiinfectious (external) and teratogenicity (subject) retrieved three questions. In the two examples, it was possible to retrieve information from any one of the levels of the hierarchy, from the most general to the most specific and even from external dimensions. Conclusions: The use of the system in this sample showed its applicability in clinical information classification and filing, retrieval capacity and flexibility, supporting modifications without interfering with desirable characteristics. This tool allows retrieval of patient-oriented evidence that matters.

Human factors required for mycobacterium tuberculosis macrophage infection

Tese de doutoramento, Farmácia (Biologia Celular e Molecular), Universidade de Lisboa, Faculdade de Farmácia, 2014

Regulatory interactions between the metabolic sensors SIRT1 and AMPK in modulating PPARα linked functions, in obesity-dependent type 2 diabetes mellitus

Tese de doutoramento, Ciências Biomédicas (Ciências Funcionais), Universidade de Lisboa, Faculdade de Medicina, 2014

Clams from Tagus estuary : microbiological, physiological and chemical responses to depuration, transpot and environmental stress

Tese de doutoramento, Biologia (Biologia Marinha e Aquacultuta), Universidade de Lisboa, Faculdade de Ciências, 2014

Estágio no Centro Hospitalar de Lisboa Norte - Polo: Hospital de Santa Maria - Serviço de Dietética e Nutrição

Relatório de estágio de mestrado, Nutrição Clínica, Universidade de Lisboa, Faculdade de Medicina, 2015

How does developmental plasticity differ between diverse types of nutrition regimes?

Tese de mestrado em Biologia Evolutiva e do Desenvolvimento, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2016

Variações genéticas do metabolismo da homocisteína como biomarcadores de risco cardiovascular em mulheres com antecedentes de doença hipertensiva da grávida

Tese de mestrado, Doenças Metabólicas e Comportamento Alimentar, Faculdade de Medicina, Universidade de Lisboa, 2013

Boletim Epidemiológico Observações: Vol. 5 (2016), Número Especial 7, Doenças Raras

Número Especial do Boletim Epidemiológico Observações dedicado às Doenças Raras. Observações é uma publicação científica trimestral do INSA, IP, que visa contribuir para o conhecimento da saúde da população, os fatores que a influenciam, a decisão e a intervenção em Saúde Pública, assim como a avaliação do seu impacte na população portuguesa. Através do acesso público e gratuito a resultados científicos gerados por atividades de observação em saúde, monitorização e vigilância epidemiológica, é dada especial atenção à disseminação rápida de informação relevante para a resposta a temas de relevo para a saúde da população portuguesa, tendo como principal alvo todos os profissionais, investigadores e decisores intervenientes na área da Saúde Pública em Portugal.