Browsing by Author "Raposo, Mafalda"
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- Cross-sectional study of risk factors for atherosclerosis in the Azorean populationPublication . Cymbron, Teresa; Raposo, Mafalda; Kazachkova, Nadia; Bettencourt, Conceição; Silva, Francisca; Santos, Cristina; Dahmani, Yahya; Lourenço, Paula C.; Ferin, Rita; Pavão, Maria Leonor; Lima, ManuelaBackground: Atherosclerosis -a major cause of vascular disease, including ischemic heart disease (IHD), is a pathology that has a two-fold higher mortality rate in the Azorean Islands compared to mainland Portugal. Aim: This cross-sectional study investigated the role of genetic variation in the prevalence of atherosclerosis in this population. Subjects and methods: A total of 305 individuals were characterized for polymorphisms in eight susceptibility genes for atherosclerosis: ACE, PAI1, NOS3, LTA, FGB, ITGB3, PON1 and APOE. Data were analysed with respect to phenotypic characteristics such as blood pressure, lipid profile, life-style risk factors and familial history of myocardial infarction. Results: In the total sample, frequencies for hypercholestrolemic, hypertensive and obese individuals were 63.6%, 39.3% and 23.3%, respectively. The genetic profile was similar to that observed in other European populations, namely in mainland Portugal. No over-representation of risk alleles was evidenced in this sample. Conclusions: One has to consider the possibility of an important non-genetic influence on the high cholesterolemia present in the Azorean population. Since diet is the most important life-style risk factor for dyslipidemia, studies aiming to evaluate the dietary characteristics of this population and its impact on serum lipid levels will be of major importance.
- Da investigação aos ensaios clínicos : desafios e oportunidades para a doença de Machado-JosephPublication . Raposo, Mafalda; Vasconcelos, João; Lima, ManuelaA União Europeia considera “rara” uma doença que afete menos do que 5 em cada 10000 pessoas. Estão atualmente descritas cerca de 7000 doenças raras, uma parte substancial das quais e de natureza genética e permanece sem tratamento ou cura. A doença de Machado-Joseph (DMJ) e uma doença globalmente rara que tem merecido especial atenção nos Açores, dada a elevada prevalência que atinge nestas ilhas. Apesar da DMJ permanecer sem intervenção farmacológica especifica, vive-se atualmente um período de grande expetativa, dada a emergência recente de resultados relativos aos primeiros ensaios clínicos. A investigação de nível clínico e alicerçada num trabalho “pré-clínico” no qual se usam, habitualmente, modelos animais (tais como o ratinho, vulgarmente designado de murganho), para avaliar e selecionar compostos com potencial suficiente para serem testados em doentes, num ensaio clínico. […].
- Doença de Machado-Joseph à procura de biomarcadores molecularesPublication . Lima, Manuela; Raposo, Mafalda; Armas, Jácome Bruges; Vasconcelos, JoãoAs doenças neurodegenerativas, das quais a doença de Parkinson ou a doença de Alzheimer são exemplos paradigmáticos, constituem patologias cuja prevalência tende a aumentar, dada a tendência global das populações para o envelhecimento. Tendo por base alterações celulares complexas, estas doenças colocam desafios ao nível do diagnostico e do tratamento, que refletem, em parte, a dificuldade em “exportar” o conhecimento proveniente da investigação, colocando-o ao serviço dos doentes (a chamada investigação bench-to-bedside). De entre as doenças neurodegenerativas, um subgrupo tem natureza hereditária. A doença de Machado-Joseph (DMJ) faz parte desse subgrupo. Trata-se de uma doença complexa, na qual vários sistemas neurológicos podem estar afetados, que se carateriza, em termos muito genéricos, pela incoordenação de movimentos, nomeadamente ao nível da marcha. Sob o ponto de vista genético, a DMJ e causada por um gene localizado no cromossoma 14; a doença, de início na idade adulta, e dominante, o que significa que basta uma dose do gene mutado (alterado), herdado a partir do pai ou da mãe, para fazer surgir a patologia. […].
- A importância das associações de doentes na investigação científicaPublication . Raposo, Mafalda; Lima, ManuelaAs doenças neurodegenerativas são doenças debilitantes nas quais ocorrem processos irreversíveis e que resultam em deterioração e/ou morte progressiva de células nervosas. Uma vez que estas doenças permanecem maioritariamente sem tratamento, a investigação científica assume-se globalmente como uma prioridade. A participação ativa dos doentes, enquanto partes interessadas, nas várias etapas da investigação é fundamental para o desenvolvimento do conhecimento científico promovendo, simultaneamente, uma cultura ética em ciência. Medidas “centradas no doente” são hoje prioritárias, por exemplo, no contexto dos ensaios clínicos, nos quais se torna importante não só perceber se uma determinada medida indica uma melhoria, na perspetiva do médico, mas também analisar o impacto do “tratamento” na sua qualidade de vida, relatado pelo doente. A aquisição, por parte dos doentes, de maior poder interventivo, nomeadamente ao nível da investigação faz-se em grande medida através de grupos organizados, dos quais as associações de doentes serão o melhor exemplo. [….].
- “ON OU “OFF”? A importância da metilação do DNA nas doenças neurodegenerativasPublication . Lima, Manuela; Vieira Melo, Ana Rosa; Teves, Luís; Raposo, MafaldaConcluído em abril de 2023, o Projeto do Genoma Humano (PGH) é considerado um dos maiores feitos científicos da história da Humanidade. O PGH gerou informação crucial acerca do nosso genoma – o conjunto das sequências formadas por combinações de quatro “letras químicas” (as bases adenina, timina, citosina e guanina), abrindo portas para avanços sem precedentes nas áreas da Biologia Humana e da Medicina. Os esforços de investigação focaram-se desde logo em sequências específicas - os genes – nas quais as bases se organizam de acordo com uma estrutura característica, com capacidade de fornecer informação para a produção de moléculas essenciais à vida tal como, por exemplo, as proteínas.
- Plasma aminothiol status in the population of the Island of São Jorge (The Azores Archipelago, Portugal)Publication . Ferin, Rita; Correia, Cristina; Raposo, Mafalda; Gonçalves, Bruno; Gonçalves, C.; Baptista, José; Pavão, Maria LeonorHcy, Cys, Cys-Gly and GSH are low molecular weight thiols that play important roles in the metabolism and homeostasis of the organism. An altered plasma aminothiols status can cause oxidative stress, thus contributing to atherogenesis. The aim of this study was to evaluate the plasma levels of total Hcy, Cys, Cys-Gly and GSH, as well as GGT activity in apparently healthy subjects from the Island of S˜ao Jorge, taking into consideration gender and lipid profile. The study group was formed by 73 subjects with no chronic diseases, aged 20 to 60 years, born living in the island of S˜ao Jorge. The evaluation of the four aminothiols was carried out by HPLC with an isocratic reversephase column using a fluorescence detector. Mean values of GSH (1.8±0.6mM) and Cys (240±35mM) content were under reference values, but Cys-Gly was above. Plasma total Hcy, Cys and Cys-Gly levels, as well as GGT activity were significantly higher in men than in women (respectively, 30%, 7%, 17% and 65%). About 63% of subjects were hyperlipidemic, mainly hypercholesterolemic. Cys concentration was increased by 9% in hyperlipidemics vs. normolipidemics. In subjects with altered thiol status men, but not women, revealed a moderate hyperhomocysteinemia. Also Cys-Gly concentrations were significantly higher in men than in women. In spite of being apparently healthy, all subjects (namely men) have depleted antioxidant defenses, indicating high oxidative stress. Alterations in plasma GSH, Cys-Gly and Cys concentrations, taken together, and independently of dyslipidemia, could be considered as early markers of atherosclerosis.
- Relationship of the APOE polymorphism and lipid profile: A population-based study in the Azores Islands (Portugal)Publication . Raposo, Mafalda; Dahmani, Yahya; Silva, Francisca; Tavares, M.; Cymbron, Teresa; Santos, Cristina; Bettencourt, Conceição; Ferin, Rita; Correia, Cristina; Pavão, Maria Leonor; Lima, ManuelaThe factors leading to a two-fold mortality rate from coronary artery disease (CAD) in the Azores, as compared to Mainland Portugal, have not been elucidated. Previous studies reported a population tendency for hypercholesterolemia, one of the main factors contributing to the development of atherosclerosis (AT), considered the primary cause of CAD. Apolipoprotein E has a key role in plasma lipid metabolism, given its function as a ligand for cell-surface receptor mediated uptake of lipoproteins. Polymorphism in the apolipoprotein gene (APOE) results in three major isoforms encoded by three codominant alleles (E2, E3 and E4). With the purpose of establishing the pattern of variation at the APOE locus and determining its association with lipid profile, we studied a random sample of 298 unrelated, apparently healthy individuals of Azorean origin. In nearly 50% of the sample total cholesterol (TC) was above 200mg/dl; in 25% of the individuals LDL-cholesterol (LDL-C) was higher than 130 mg/dl. Allele frequencies were 0.0833, 0.8317 and 0.0850 for E2, E3 and E4, respectively. Genotype frequencies were higher for E3*E3 genotype (66.1%); genotype distribution displayed conformity with Hardy-Weinberg expectations. No differences in allelic frequencies were found in comparison with other Caucasian populations, namely with mainland Portugal. E3*E4 individuals presented the highest cholesterol levels. Analysis of variance performed with the most represented genotypes (E2*E3, E3*E3 and E3*E4) revealed a clear association between the genotypic composition and TC, as well as LDL-C, thus confirming in this population, the role of APOE as one of the genetic determinants of AT.
- Serum atherogenic lipid markers in subjects from three islands of The Azores Archipelago (Portugal): a comparison studyPublication . Ferin, Rita; Correia, Cristina; Raposo, Mafalda; Castro, Ana Rita; Reis, C.; Vieira, T.; Gonçalves, Bruno; Pavão, Maria LeonorSão Miguel (SM), Graciosa (GR) and São Jorge (SJ) are three islands of the Azores’ Archipelago, where the death rate from coronary artery disease is abouttwice than in mainland Portugal. The aim of this study was to evaluate and compare serum atherogenic lipid markers as reflected by lipid profile, as well as by apoB/apoA-1 ratio in apparently healthy subjects from those islands. The study group was formed by 321 subjects with no chronic diseases, aged 20 to 60 years, born living in the respective island (156 from SM, 92 from GR and 73 from SJ). In all cases, about 64% of subjects were hyperlipidemic, mainly hypercholesterolemic. LDL-C and HDL-C concentrations were respectively, lower and higher in SM than in SJ or GR. ApoB concentration was 40% and 17% higher in SJ than in SM and GR, respectively, while apoA-1 reached the maximum in SM (178±38 mg/dL). Regarding apoB/apoA-1 ratio, taken as a better atherogenic marker then conventional lipid profile, subjects from GR exhibited the highest mean value (0.85±0.4), followed by those from SJ (0.75±0.3) and SM (0.58±0.2). Particularly in men from GR and SJ, ratios were 1.0 and 0.9, respectively, which corresponds to a high risk of developing a cardiovascular incident.