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Browsing by Author "Mota-Pinto, A"

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  • Aging and asthma - changes in CD45RA, CD29 and CD95 T cells subsets
    Publication . Todo-Bom, A; Mota-Pinto, A; Alves, V; Santos-Rosa, M
    BACKGROUND: Aging is associated with thymus involution leading to a reduction in naive T cells and to an accumulation of effector-memory cells. Apoptosis is a key mechanism to clear the immune system from activated and harmful cells. In asthma the stimulation of T cells by environmental antigens can decrease naive cells and sustain activated cells. The aim of this work was to evaluate the imbalance between CD45RA and CD29 cells during the aging process and their changes in elderly asthma and to evaluate how elderly and chronic diseases like asthma can affect susceptibility to apoptosis. METHODS: Elderly and young adult healthy volunteers and elderly asthmatic patients were submitted to skin prick tests, immunoglobulin determination and flow cytometry analyses of CD3, CD4, CD8, CD45RA, CD29, and CD95. RESULTS: Serum IgE was increased in allergic patients (p=0.0001). Asthmatics presented an increase in CD4 cells (p<0.05). CD45RA was significantly decreased in elderly individuals (p<0.05) and this decrease was higher in asthmatics (p<0.05). CD29 was increased in elderly healthy individuals compared to the control young group (p=0.0001). A negative correlation between CD29 and CD45RA (p<0.05) was observed. CD95 lymphocytes increased in elderly (p=0.0001) and a positive correlation between age and CD95 (p<0.05) was found. Asthmatic patients showed significant decreases in CD95 (p=0. 0001). CONCLUSIONS: Naive cells are key cells in the defence against infections and their decrease in the elderly and in asthma is a bad prognosis factor. The reduction of apoptosis markers can promote the persistence of activated cells involved in chronic conditions.
    2011Journal article Open access Show more
  • Allergic respiratory diseases in the elderly
    Publication . Todo-Bom, A; Mota-Pinto, A
    In industrialized countries there has been a significant increase in life expectancy, but chronic diseases are still important causes of death and disability in the elderly. Individuals over 65 years of age have a decrease in organic functions and lungs can lose more than 40% of their capacity. Although asthma and allergic rhinitis are more common in young people their prevalence in the elderly is increasing and the mortality reported in these patients is high. Asthmatic airways show an accumulation of activated eosinophils and lymphocytes determining structural changes of the bronchi. Local allergic inflammation, changes in T cell phenotypes and in apoptosis contribute to systemic inflammation. An increased risk of respiratory infections and neoplasic diseases has been recognized. These patients have increased susceptibility to atherosclerosis and cardiovascular diseases. Metabolic diseases are associated with an impairment of lung function and with systemic inflammation. Summing up older asthmatic patients have an increased risk to premature disability and death. A proper therapeutic approach to asthma can minimize this evolution. To identify the triggers is an important goal that allows reducing medication needs. Corticosteroids dampen allergic inflammation; therefore, they are the first choice in the treatment of patients with persistent asthma and rhinitis. Second-generation H1 receptor antagonists have reduced side effects and can be used if necessary. The elderly may have difficult access to health care. They should be educated about their disease and receive a written treatment plan. This information improves the quality of life, socialization and disease outcome in older people.
    2009Journal article Open access Show more
  • Apoptosis and asthma in the elderly
    Publication . Todo-Bom, A; Mota-Pinto, A; Alves, V; Vale-Pereira, S; Santos-Rosa, M
    BACKGROUND: Asthma is a chronic inflammatory disorder of the airways. The persistence of airway inflammation depends on a decrease in apoptosis of T lymphocytes and eosinophils and survival of these activated cells. T lymphocytes expressing gamma delta receptors can be identified in human lungs and play an important role in immune defence against pathogens and in the regulation of chronic inflammation. Aging is associated with evidence of some immune dysregulation. OBJECTIVE: The aim of this study was to analyze the apoptosis receptors of T lymphocytes in long-lasting asthma, to establish their correlation with activation markers such as CD25+ and human leukocyte antigen (HLA)-DR+, and to analyze the gama delta T cell expression in this disease. METHODS: A group of 64 individuals (group A) who had had asthma for more than 30 years (mean age [+/-SD] 72 +/- 5 years) and 61 healthy individuals acting as controls--group B with 41 individuals (mean age 79 +/- 7 years) and group C with 20 individuals (mean age 38 +/- 12 years) were included in the study. All subjects underwent clinical evaluation and spirometric testing. Peripheral blood cells were stained with monoclonal antibodies anti-CD3, anti-CD4, anti-CD8, anti-CD25, anti-TCR gamma delta, anti-HLA-DR and anti-CD95. Statistical comparisons were performed between the asthmatics and the elderly control group and between the elderly control group and the adult control group. RESULTS: The average percentage of predicted forced expiratory volume in the first second was 73.6 gamma delta 25.3. The mean values of T cell receptors for asthma group A vs elderly control group B vs adult control group C respectively, were the following: CD3, 74.9+/-7 vs. 74.8 +/- 8.8 (P=ns) vs. 76.7 +/- 4.2 (P=ns); CD4, 48.8 +/- 8.7 vs. 43.5 +/- 10.2 (P=ns) vs. 44.8 +/- 3.8 (P=ns); CD8, 23.3 +/- 7.9 vs. 25.7 +/- 10.2 (P=ns) vs. 25.6 +/- 4.5 (P=ns); CD25, 14.3 +/- 5.9 vs. 22.4 +/- 7.8 (P = .0001) vs. 5.5 +/- 2.4 (P = .0001); TCR gamma delta, 2.8 +/- 2.1 vs. 4.1 +/- 3.3 (P < .05) vs. 4.6 +/- 2.1 (P=ns); HLA-DR, 18.4 +/- 9.2 vs. 17.8 +/- 5.9 (P=ns) vs. 15.4 +/- 5.1 (P=ns) and CD95, 49.3 +/- 13.7 vs. 52.6 +/- 12.1 (P=ns) vs. 13.8 +/- 10.8 (P = .0001). CONCLUSIONS: The immunological and inflammatory changes related to ageing may cause an increase in CD95 and CD25 T cell expression. In asthma, blood cells may express increased activation and apoptosis markers but in elderly patients taking steroids, these receptors remain within normal ranges. The number of gamma delta T cells may be lower in long-lasting asthma, and have a limited modulatory effect on allergic inflammatory reactions. The evaluation of patients with long-lasting asthma should take into account the immunological and inflammatory changes present in the elderly in order to avoid results being misinterpreted
    2007Journal article Open access Show more
  • Asma: Reflexo da apoptose e de fenótipos de regulação
    Publication . Todo-Bom, A; Mota-Pinto, A; Alves, V; Vale-Pereira, S; Chieira, S; Santos-Rosa, M
    A asma é uma doença inflamatória crónica das vias aéreas, e os linfócitos T desempenham um papel central na sua patogénese. Na inflamação alérgica quer os eosinófilos quer os linfócitos T podem ter um tempo de vida aumentado no local da inflamação, por redução da apoptose, mantendo-se activados. No pulmão encontra-se uma subclasse de linfócitos T que expressa receptor γδ. Estes linfócitos T γδ (TCRγδ) representam 1 a 10% dos linfócitos maduros circulantes e desempenham funções importantes na primeira linha de defesa imunitária contra agentes microbianos, na inflamação alérgica e na regulação da inflamação crónica. O objectivo deste estudo consistiu na análise de linfócitos T na asma persistente de evolução arrastada em doentes idosos no que concerne à expressão de receptores de apoptose, na sua correlação com marcadores de activação (CD25 e HLADR) e ainda à expressão TCR γδ nesta doença crónica comparativamente a indivíduos saudáveis do mesmo grupo etário e a indivíduos saudáveis adultos. Foram incluídos no estudo 64 doentes asmáticos (72±5 anos), com mais de 30 anos de evolução da doença e um grupo-controlo com 61 indivíduos, dividido em dois subgrupos de 41 indivíduos idosos (79±7 anos) e de 20 indivíduos adultos (38±12 anos). Todos os doentes foram avaliados do ponto de vista clínico e realizaram uma espirometria com Vitalograph Compact. As células do sangue periférico foram marcadas com anticorpos monoclonais anti-CD3, anti-CD4, anti-CD8, anti-CD25 anti-TCR γδ, anti-HLA-DR e anti- -CD95. A análise estatística direccionou-se a comparar asmáticos com controlo-idosos e controlo-idosos com controlo- -adultos. A percentagem média de forced expiratory volume in the first second (FEV1) foi de 73,6±25,3. Relativamente aos receptores estudados, obtiveram-se os seguintes resultados em asmáticos vs controlo-idosos vs controlo-adultos: CD3: 74,9±7 vs 74,8±8,8 vs 76,7±4,2; CD4: 48,8±8,7 vs 43,5±10,2 vs 44,8±3,8; CD8: 23,3±7,9 vs 25,7± 10,2 vs 25,6±4,5; CD25: 14,3±5,9 vs 22,4±7,8 (p=0,000) vs 5,5 ±2,4 (p=0,000); TCR γδ: 2,8±2,1 vs 4,1 ± 3,3 (p<0,05) vs 4,6±2,1; HLA-DR: 18,4± 9,2 vs 17,8± 5,9 vs 15,4± 5,1 e CD95: 49,3±13,7 vs 52,6±12,1 vs 13,8± 10,8 (p=0,000). Em conclusão, as alterações imunológicas e inflamatórias associadas à idade determinam um aumento da expressão nos linfócitos T de CD25 e de CD95. Na asma, a probabilidade de células do sangue periférico expressarem um maior número de marcadores de activação e uma redução de marcadores de apoptose pode ser limitada nas formas estáveis da doença, não introduzindo modificações significativas às determinadas pelo envelhecimento. Os linfócitos T γδ podem estar reduzidos na asma com evolução arrastada, podendo por isso exercer uma acção modesta na modulação da inflamação e contribuir para a cronicidade destas situações clínicas. Sendo a asma uma doença crónica irreversível qualquer análise ou interpretação fisiopatológica efectuada em formas tardias e arrastadas tem necessariamente de considerar as alterações decorrentes do processo de envelhecimento. A ausência de análise destes dados pode promover interpretações menos rigorosas, com ilações terapêuticas desajustadas.
    2007Journal article Open access Show more
  • Asthma and rhinitis have different genetic profiles for IL13, IL17A and GSTP1 polymorphisms
    Publication . Resende, EP; Todo-Bom, A; Loureiro, C; Mota-Pinto, A; Oliveiros, B; Mesquita, L; Silva, HC
    BACKGROUND: Asthma and rhinitis have a complex etiology, depending on multiple genetic and environmental risk factors. An increasing number of susceptibility genes are currently being identified, but the majority of reported associations have not been consistently replicated across populations of different genetic backgrounds. PURPOSE: To evaluate whether polymorphisms of IL4R (rs1805015), IL13 (rs20541), IL17A (rs2275913) and GSTP1 (rs1695) genes are associated with rhinitis and/or asthma in adults of Portuguese ancestry. METHODS: 192 unrelated healthy individuals and 232 patients, 83 with rhinitis and 149 with asthma, were studied. All polymorphisms were detected by real time polymerase chain reaction (PCR) using TaqMan assays. RESULTS: Comparing to controls, significant association with asthma was observed for GSTP1 rs1695 AA genotype (odds ratio (OR) - 1.96; 95% CI - 1.18 to 3.25; p=0.010). The association sustains for allergic asthma (OR - 2.17; 95% CI - 1.23 to 3.80; p=0.007). IL13 rs20541 GG genotype was associated with less susceptibility to asthma (OR - 0.55, 95% CI - 0.33 to 0.94, p=0.028). Among patients, IL17A rs2275913 AA genotype was less associated with asthma than with rhinitis (OR - 0.20; 95% CI of 0.07 to 0.56; p=0.002). A similar association was found for IL13 rs20541 GG genotype (OR - 0.48; 95% CI of 0.25 to 0.93; p=0.031). There were no significant differences in the distribution of allelic and genotypic frequencies between patients and controls for the IL4R polymorphism' analyzed. CONCLUSION: These results support the existence of a significant association between GSTP1 rs1695 and IL13 rs20541 SNPs, with susceptibility to asthma, in the population studied. Different genotype profiles of IL17A and IL13 genes seem to influence the clinical pattern of disease expression mainly confined to the upper airways, as rhinitis, or including the lower airways, as asthma.
    2016-08-22Journal article Open access Show more
  • Determinação da neopterina e de defesas antioxidantes na asma de evolução arrastada
    Publication . Mota-Pinto, A; Todo-Bom, A; Vale-Pereira, S; Alves, V; Santos-Rosa, M
    Asthma is a condition characterised by a chronic immunoinflammatory response to different triggers. Neopterin (NPT) is synthesised by human macrophages upon stimulation with interferon-gamma and is also capable of enhancing the oxidative potential of reactive oxygen species. NPT is useful for the monitoring of cell-mediated (Th1-type) immune activation. This study analysed the behaviour of NPT in long lasting asthma, considering its role as a marker of Th1 environment. Allergic parameters (skin prick tests, Immunoglobin E (IgE), and eosinophil count) and NPT were evaluated in an asthmatic group and in a control group. We also analysed the C Reactive Protein (CRP) concentration, Total Antioxidant Status (TAS) and Superoxide Dismutase Enzyme (SOD) in both groups. A group of individuals aged over 65 years old was selected. It included 64 asthmatic patients (72+/-5 years) and 41 healthy individuals (79+/-7 years). Blood cell counts showed statistically different median values of eosinophils (5.42+/-4.7 vs 2.8+/-2.8;p<.04), IgE (493.2+/-549.8 vs 85.3+/-194.UI/ml; p=.000) and NPT was non-statistically decreased (2.4+/-2.8 vs 4.0+/-4.7 ng/ml) in allergic asthmatic patients when compared with non-allergic asthmatic patients. Both allergic and non-allergic asthmatic patients presented a statistically significant decreased expression of TAS (0.84+/-0.14/0.86+/-0.11 vs 0.91+/-0.10 mM) and SOD (584.8+/-108.7/595.6+/-235.9 vs 822.9+/-179.5) when compared with normal control subjects. Our results suggest macrophage involvement in asthma pathogenesis. The deficit in antioxidant defence impacts negatively on this disease. The increase of NPT values in non-allergic asthma consolidates these affirmations and mapping this parameter should be part of the work of an analytical study panel as it may lead to allergic asthma being distinguished from non- allergic asthma.
    2006Journal article Open access Show more
  • Doseamento das granzimas A e B na sarcoidose pulmonar (estudo experimental)
    Publication . Dourado, M; Bento, J; Mesquita, L; Marques, A; Vale-Pereira, S; Ribeiro, AB; Mota-Pinto, A
    Sarcoidosis is a systemic disease of unknown aetiology, morphologically characterized by well-formed epithelioid granulomas, which show little or no central necrosis. These may be present in any organ or tissue. The lung is the most frequently and prominently involved target. The granuloma is often very sharply demarcated from the adjacent tissue and is surrounded by a mantle of lymphocytes, which mediate lysis of target cells by various mechanisms, including exocytosis of lytic proteins, perforins and granzymes. Sarcoidosis laboratorial diagnosis is usually made by SACE and Lisozyme dosages. The granzymes A and B could be two other markers of the disease, since the sarcoidosis granuloma is rich in cytotoxic and NK cells. An ELISA Kit was used to measure Granzyme A and B in serum of a normal control group (NC) (n=30), and in two groups with lung pathology: one without sarcoidosis, disease control (DC) (n=21) and other with sarcoidosis (S) (n=11). Our results showed that SACE activity is significantly augmented in S group comparing with NC and DC, respectively: 82,6+/-32,7/31,9+/-17,8 - p=0,00017 and 82,6+/-32,7/31,9+/-17,8 - p=0,00024. Lisozyme activity is significantly augmented in S and DC groups comparing with NC. Granzyme B showed a significant decrease in DC and S groups comparing with NC. Granzyme A showed a significant decrease between S/NC groups. Our results suggest that the decrease of Granzyme A and B in sarcoidotic patients could be related to an ineffective inflammatory local response related to the formation of sarcoidosis granulomas. More studies are needed, particularly in BAL.
    2005Journal article Open access Show more
  • Elevated neopterin levels in non-allergic asthma
    Publication . Mota-Pinto, A; Todo-Bom, A; Vale-Pereira, S; Alves, V; Santos-Rosa, M
    Neopterin is synthesized by human monocyte-derived macrophages upon stimulation with interferon-gamma (IFN-gamma). Measurement of neopterin concentration is useful to monitor cell-mediated (Th1-type) immune activation. In this study, we aimed to analyze the behaviour of neopterin in long lasting asthma considering its role as a marker of the Th1 environment and to establish the distinction between patients belonging either to the allergic or the non-allergic population, particularly in the elderly where asthma is often under diagnosed. Therefore we evaluated allergic parameters such as skin prick tests, IgE and hemogram (eosinophils count), and we compared our findings with neopterin values found in an age-matched control population. A group of individuals older than 65 was selected. It included 64 asthmatic patients (mean age 72+/-5 years) and 41 healthy individuals (mean age 79+/-7 years). In our study population, 42 patients presented positive skin tests, mainly to house dust mites. All patients were clinically stable and presented an average percentage of predicted forced expiratory volume in the first second (FEV1) of 73.6+/-25.3 and predicted median expiratory flow percentage (MEF50) of 38.8+/-26.7. Blood cell counts showed statistically different mean values of eosinophils between allergic and non-allergic controls (5.42+/-4.7% versus 2.8+/-2.8%; p<0.04). IgE values were increased in allergic asthmatic patients when compared with non-allergic asthmatic patients (493.2+/-549.8IU/ml versus 85.3+/-194.4IU/ml; p=0.000). Allergic asthmatic patients presented mean neopterin levels similar to those found in the control group (2.4+/-2.8ng/ml versus 2.1+/-1.9ng/ml). In contrast, in non-allergic asthmatic patients these values were higher when compared with the control group (4.0+/-4.7ng/ml versus 2.1+/-1.9ng/ml). Neopterin levels were lower in allergic asthmatic patients when compared with non-allergic asthmatic patients (2.4+/-2.8ng/ml versus 4.0+/-4.7ng/ml). Within asthmatic patients, those with higher neopterin values (>2.1ng/ml) presented lower mean IgE values (IgE
    2006Journal article Open access Show more
  • Estudo do perfil do envelhecimento da população portuguesa
    Publication . Oliveira, CR; Santos-Rosa, M; Mota-Pinto, A; Botelho, MA; Morais, A; Veríssimo, MT
    2010Book Open access Show more
  • Exercício físico: Resposta imunoinflamatória
    Publication . Todo-Bom, A; Mota-Pinto, A
    O estudo da relação entre o exercício e a resposta inflamatória e imunológica tem motivado um elevado interesse, desde há vários anos. Existe uma estreita comunicação entre o sistema neuroendócrino e as células imunocompetentes através de mensageiros que vão ter uma intervenção importante nessa resposta. O exercício físico determina em geral uma imunossupressão transitória, precedida de um aumento da componente celular e humoral de intensidade e duração variáveis, dependendo da natureza do exercício e da susceptibilidade específica aos mediadores libertados. Os leucócitos totais, particularmente os neutrófilos e células natural killer mantêm-se elevados no período que se segue ao exercício intenso, enquanto os linfócitos tendem rapidamente a atingir contagens semelhantes ou inferiores aos valores pré-exercício. O exercício intenso pode favorecer um desvio do fenótipo linfocitário Th1 para o fenótipo Th2. As imunoglobulinas, particularmente a IgG, tendem a aumentar transitoriamente. As proteínas de fase aguda e as citocinas, principalmente a IL6 e TNFα, terão intervenções particularmente destacadas neste processo. A prática regular de desporto moderado induz um retorno à estabilidade basal da maioria dos parâmetros, bem como a uma protecção acrescida relativamente a agressores microbianos ambientais. Esta observação está limitada pela dificuldade em distinguir uma actividade moderada continuada de um esforço físico intenso cíclico, sendo contudo certo que os benefícios na saúde atribuídos ao exercício físico moderado estão em larga medida relacionados com as modificações que provocam no sistema inflamatório e imunológico.
    2007Journal article Open access Show more