Browsing by Author "Costa, L."
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- Alterações fenotípicas e genéticas do metabolismo do ferro numa população portuguesa com doença de Alzheimer: potenciais implicações no conhecimento da fisiopatologia e no diagnóstico desta demênciaPublication . Crespo, A.C.; Silva, B.; Marques, L.; Marcelino, E.; Maruta, C.; Costa, S.; Timóteo, A.; Vilares, A.; Couto, F.S.; Faustino, Paula; Correia, A.P.; Verdelho, A.; Porto, G.; Guerreiro, M.; Herrero, A.; Costa, C.; Mendonça, A.; Martins, M.; Costa, L.
- Analysis of Genetic Markers for Cardiovascular Disorders in a Portuguese population with Familial HypercholesterolaemiaPublication . Gomes, A.; Santos, T.; Costa, L.; Bourbon, M.Familial Hypercholesterolaemia is a genetic disorder characterized by an increase in TC and LDLC leading to premature atherosclerosis (ATH) and cardiovascular disorders (CVD) but not all FH patients develops premature CVD. Early identification of FH patients at an even increased risk of developing CVD is important. Genetic markers could improve risk stratification for this patients. Inflammation has been considered to be involved in the pathogenesis of CVD and genetic and oxidative stress markers may also contribute to ATH and CVD outcome.
- Analysis of Genetic Markers for Cardiovascular Disorders in a Portuguese Population with Familial HypercholesterolaemiaPublication . Gomes, A.; Santos, T.; Costa, L.; Bourbon, M.Familial Hypercholesterolaemia (FH) is a genetic disorder that leads to an increase in levels of total and low density lipoprotein cholesterol promoting atherosclerosis (ATH) and premature cardiovascular disease (CVD). ATH and CVD are multifactorial disorders depending on both genetic and environmental factors and inflammation has been considered to be involved in the pathogenesis of ATH and CVD, namely the activity of pro-inflammatory cytokines and acute phase proteins. Also, there are other risk factors contributing to the development and progression of ATH and CVD as genetic and oxidative stress markers.
- Ceruloplasmin expression by human peripheral blood lymphocytes: a new link between immunity and iron metabolismPublication . Banha, J.; Marques, L.; Oliveira, R.; Martins, M. de F.; Paixão, E.; Pereira, D.; Malhó, R.; Penque, D.; Costa, L.Ceruloplasmin (CP) is a multicopper oxidase involved in the acute phase reaction to stress. Although the physiological role of CP is uncertain, its role in iron (Fe) homeostasis and protection against free radical-initiated cell injury has been widely documented. Previous studies showed the existence of two molecular isoforms of CP: secreted CP (sCP) and a membrane glycosylphosphatidylinositol (GPI)-anchored form of CP (GPI-CP). sCP is produced mainly by the liver and is abundant in human serum whereas GPI-CP is expressed in mammalian astrocytes, rat leptomeningeal cells, and Sertolli cells. Herein, we show using RT-PCR that human peripheral blood lymphocytes (huPBL) constitutively express the transcripts for both CP molecular isoforms previously reported. Also, expression of CP in huPBL is demonstrated by immunofluorescence with confocal microscopy and flow cytometry analysis using cells isolated from healthy blood donors with normal Fe status. Importantly, the results obtained show that natural killer cells have a significantly higher CP expression compared to all other major lymphocyte subsets. In this context, the involvement of lymphocyte-derived CP on host defense processes via its anti/prooxidant properties is proposed, giving further support for a close functional interaction between the immune system and the Fe metabolism.
- Crosstalk between inflammation, iron metabolism and endothelial function in Behçet’s diseasePublication . Oliveira, R.; Napoleão, P.; Banha, J.; Paixão, E.; Bettencourt, A.; M da Silva, B.; Pereira, D.; Barcelos, F.; Teixeira, A.; Vaz Patto, J.; Viegas-Crespo, A.M.; Costa, L.Behçet's disease (BD) is a rare chronic vasculitis of unclear etiology. It has been suggested that inflammatory response has an important role in BD pathophysiology. Herein, we aimed to study the interplay between inflammation, iron metabolism and endothelial function in BD and search for its putative association with disease activity. Twenty five patients clinically diagnosed with BD were selected and twenty four healthy age-sex matched individuals participated as controls. Results showed an increase of total number of circulating white blood cells and neutrophils, serum transferrin, total iron binding capacity, mieloperoxidase (MPO), ceruloplasmin (Cp), C reactive protein, β2 microglobulin and Cp surface expression in peripheral blood monocytes in BD patients comparatively to healthy individuals (p < 0,05). Of notice, the alterations observed were associated to disease activity status. No significant differences between the two groups were found in serum nitric oxide concentration. The results obtained suggest an important contribution from innate immunity in the pathogenesis of this disease. In particular, surface expression of leukocyte-derived Cp may constitute a new and relevant biomarker to understand BD etiology.
- Developing a Training Programme in Health Impact Assessment (HIA) in PortugalPublication . Costa, A.; Costa, L.; Gulis, G.; Nowacki, J.; Caldas de Almeida, T.Objectives: To build technical expertise and capacity to assessand evaluate policies, plans, programs and projects using HIA methodology; To develop a HIA toolkit,validated for usein Portuguese contexto based on national case studies.
- Differential Regulation of Ceruloplasmin Isoforms Expression in Macrophages and HepatocytesPublication . Marques, L.; Auriac, A.; Willemetz, A.; Banha, J.; Silva, B.; Canonne-Hergaux, F.; Costa, L.Ceruloplasmin (Cp) is an acute-phase protein that has been implicated in iron metabolism due to its ferroxidase activity, assisting ferroportin (Fpn) on cellular iron efflux. However, Cp exhibits both anti- and pro-oxidant activities and its physiological functions remain unclear. Cp can be expressed as a secreted or as a membrane glycosylphosphatidylinositol-anchored protein (GPI-Cp), this latter one being mostly expressed in the brain. Herein, we studied the expression of both Cp isoforms in human peripheral blood lymphocytes, monocytes, mouse macrophages and human hepatocarcinoma cell line HepG2, using immunofluorescence and immunoblotting techniques. Co-localization of Cp and Fpn was also investigated by immunofluorescence in mouse macrophages. Cp was detected by immunoblotting and immunofluorescence in membrane and cytosol of all cells types studied. The Cp detected at cell surface was identified as the GPI-isoform by PI-PLC test and shown to localize in lipid rafts in monocytes, macrophages and HepG2 cells. In macrophages, increased expression levels and co-localization of Fpn and GPI-Cp at cell surface lipid rafts were observed after iron treatment. Such upregulation of Cp by iron was not observed in HepG2 cells. Our results revealed an unexpected ubiquitous expression of the GPI-Cp isoform in immune and hepatic cells. A differential regulation of Cp in these cells may reflect distinct physiological functions of this oxidase according to cell-type specificity. In macrophages, GPI-Cp and Fpn likely interact in lipid rafts to export iron. A better insight into the expression of both Cp isoforms in different cell types will help to clarify its role in many diseases related to iron metabolism, inflammation and oxidative biology.
- Estudo-piloto de Health Impact Assessment sobre os possíveis efeitos da redução do sal no pão na doença cardiovascularPublication . Costa, L.; Costa, A.; Braz, P.; Santos, J.; Santos, M.; Brazão, R.; Guerreiro, A.; Lopes, I.; Alves, J.; Caldas de Almeida, T.As doenças cardiovasculares (DCV) representam atualmente uma das principais causas de morte em Portugal, sendo o consumo excessivo de sal um dos fatores de risco. A redução do consumo de sal é considerada uma das melhores abordagens (best buys) para a prevenção destas doenças. Considerando que o pão é um dos principais alimentos que contribuem para a ingestão de sal pela população portuguesa, foi assinado em outubro de 2017, um protocolo entre a Direção-Geral da Saúde, o Instituto Nacional de Saúde Doutor Ricardo Jorge e as Associações dos Industriais da Panificação, Pastelaria e Similares, com o objetivo de reduzir o teor de sal no pão. Este protocolo foi escolhido para a realização de um estudo piloto utilizando a metodologia de Health Impact Assessment (HIA). O HIA combina procedimentos e métodos que permitem analisar os potenciais impactes de projetos, programas ou políticas, na saúde da população e sua distribuição. Objetivo: Desenvolver um estudo piloto de HIA para avaliar o possível impacte nas DCV da população portuguesa resultante da redução do sal adicionado ao pão, de acordo com as metas estabelecidas no referido protocolo.
- Genetic and biochemical markers in patients with Alzheimer's disease support a concerted systemic iron homeostasis dysregulationPublication . Crespo, A.C.; Silva, B.; Marques, L.; Marcelino, E.; Maruta, C.; Costa, S.; Timóteo, A.; Vilares, A.; Couto, F.S.; Faustino, Paula; Correia, A.P.; Verdelho, A.; Porto, G.; Guerreiro, M.; Herrero, A.; Costa, C.; de Mendonça, A.; Costa, L.; Martins, M.Alzheimer's disease (AD) is the most common form of dementia in the elderly individuals, resulting from a complex interaction between environmental and genetic factors. Impaired brain iron homeostasis has been recognized as an important mechanism underlying the pathogenesis of this disease. Nevertheless, the knowledge gathered so far at the systemic level is clearly insufficient. Herein, we used an integrative approach to study iron metabolism in the periphery, at both genotypic and phenotypic levels, in a sample of 116 patients with AD and 89 healthy control subjects. To assess the potential impact of iron metabolism on the risk of developing AD, genetic analyses were performed along with the evaluation of the iron status profile in peripheral blood by biochemical and gene expression studies. The results obtained showed a significant decrease of serum iron, ferritin, and transferrin concentrations in patients compared with the control subjects. Also, a significant decrease of ferroportin (SLC40A1) and both transferrin receptors TFRC and TFR2 transcripts was found in peripheral blood mononuclear cells from patients. At the genetic level, significant associations with AD were found for single nucleotide polymorphisms in TF, TFR2, ACO1, and SLC40A1 genes. Apolipoprotein E gene, a well-known risk factor for AD, was also found significantly associated with the disease in this study. Taken together, we hypothesize that the alterations on systemic iron status observed in patients could reflect an iron homeostasis dysregulation, particularly in cellular iron efflux. The intracellular iron accumulation would lead to a rise in oxidative damage, contributing to AD pathophysiology.
- Health Impact Assessment: Uma Ferramenta de Apoio à Adoção de Políticas Saudáveis na Área da AlimentaçãoPublication . Costa, L.; Costa, A.; Braz, P.; Santos, J.; Santos, M.; Assunção, R.; Brazão, R.; Guerreiro, A.; Lopes, I.; Alves, J .; Caldas Almeida, T .Introdução: O Health Impact Assessment (HIA) combina procedimentos e métodos que avaliam potenciais impactes de projetos, programas ou politicas na saúde e a sua distribuição nas populações. Visa informar e melhorar o processo de tomada de decisão baseada na melhor evidência disponível. Devidamente integrado nos processos de planeamento estratégico, o HIA pode contribuir para a implementação de “Políticas Saudáveis”, tal como definido num dos quatro eixos do Plano Nacional de Saúde. É, assim, um instrumento importante para a concretização de uma abordagem integrada da Saúde em todas as políticas. Objetivo: Desenvolver competências técnicas na área do HIA numa perspetiva de learning by doing, através da capacitação de profissionais de saúde e de outros setores.