Browsing by Author "Pacheco, Paula"
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- A comprehensive overview of the cystic fibrosis on the island of São Miguel (Azores, Portugal)Publication . Rosa, Joana; Gaspar-Silva, Patrícia; Pacheco, Paula; Silva, Conceição; Branco, Cláudia C.; Vieira, Barbara S.; Carreiro, Alexandra; Gonçalves, Juan; Mota-Vieira, LuisaBackground: Early diagnosis and treatment are improving significantly the quality of life of patients with cystic fibrosis (CF). This recessive disease is caused by a great variability of mutations in the CF transmembrane conductance (CFTR) gene, whose spectrum and frequency can be different across populations. Methods: We performed a retrospective cross-sectional study of CF patients from the island of São Miguel (Azores, Portugal) through a clinical, genealogical, genetic and epidemiological investigation. The clinical course of patients was analyzed as a whole and according to their genotype. Results: We identified 14 CF patients within a 23-year period, corresponding to a cumulative incidence of 1:3012 births, being three of them born from consanguineous unions. Genetic analysis revealed three CFTR genotypes: p.[Ser4Ter];[Gln1100Pro] was present in one patient with a less severe phenotype (1/14); c.[120del23];p.[Phe508del], a very rare one (2/14); and p.[Phe508del];[Phe508del] in the remaining patients (11/14). Clinically, respiratory infections (8/14) and growth failure (6/14) were the most common initial manifestations. All patients presented pancreatic dysfunction, with 21.4 and 100% of them showing endocrine and exocrine insufficiency, respectively. As expected, patients with severe phenotype were homozygous for p.Phe508del and had the lowest value of body mass index. Conclusions: The present study demonstrated that São Miguel Island has an increased incidence of CF when compared to recent Portuguese data (1:7500 live births). It also allowed a comprehensive overview of CF in São Miguel, improving medical practice along with genetic counselling and creating opportunities for genotype-targeted therapies.
- Diagnóstico da Fibrose Quística: a prova do suor como técnica de referência para o seu diagnósticoPublication . Alvim, Marta; Costa, Alcina; Gomes, Filomena; Almeida, Suza; Silva, Conceição; Pacheco, PaulaA Fibrose Quistica (FQ) é a doença genética autossómica recessiva letal mais frequente na população caucasiana. É causada por mutações no gene que codifica a proteína CFTR (Cystic Fibrosis Transmembrane Condutance Regulator), que funciona como canal de transporte de iões Cloreto ao nível da membrana apical das células epiteliais, contribuindo para o controlo do movimento de água nos tecidos. A FQ é caracterizada pela obstrução e infecção pulmonar crónica, insuficiência pancreática, obstrução intestinal, infertilidade masculina e suor com níveis elevados de cloretos. A idade em que se começam a manifestar os sintomas e a sua gravidade estão relacionadas com o tipo de mutações no gene CFTR. O diagnóstico é baseado no fenótipo clínico associado a duas ou mais provas do suor positivas e/ou pela presença de duas mutações no gene CFTR. O presente trabalho tem como objetivo avaliar a casuística da Prova do Suor entre 2009 e Março de 2018 realizado no Departamento de Promoção da Saúde e Prevenção de Doenças não Transmissíveis do INSA, I.P Lisboa e o estudo do gene CFTR, efetuado na Unidade de Genética Molecular, Departamento de Genética Humana, INSA, I.P Lisboa. Foram analisados 594 indivíduos, com idades entre um mês e os 77 anos, sendo que a maioria dos indivíduos, 79,5%, tem até aos 12 anos de idade. Em relação ao género a distribuição da amostragem é aproximada igual, com 43,36% das amostras do sexo feminino e 56,64% do sexo masculino.
- Fibrose quística: diagnóstico laboratorial pela prova do suor num grupo populacionalPublication . Costa, Alcina; Batalha, Lídia; Almeida, Suza; Vilares, Arminda; Pacheco, Paula; Silva, Conceição; Miranda, Armandina
- Prova do Suor no Diagnóstico Laboratorial da Fibrose QuisticaPublication . Costa, Alcina; Batalha, Lídia; Almeida, Suza; Vilares, Arminda; Pacheco, Paula; Silva, Conceição; Miranda, ArmandinaObjectivo: Apresentar a casuística da Prova do Suor, no período de 2009 a 2013 da UDR do DPS do INSA, I.P. Lisboa , e o estudo do gene CFTR, efetuado na Unidade de Genética Molecular, Departamento de Genética Humana, INSA, I.P. Lisboa.
- SELDI-TOF biomarker signatures for cystic fibrosis, asthma and chronic obstructive pulmonary diseasePublication . Gomes-Alves, Patrícia; Imrie, Margaret; Gray, Robert D.; Nogueira, Paulo; Ciordia, Sergio; Pacheco, Paula; Azevedo, Pilar; Lopes, Carlos; De Almeida, António Bugalho; Guardiano, Micaela; Porteous, David J.; Albard, Juan P.; Boyd, A. Christopher; Penque, DeborahOBJECTIVES: The aim of this work was to establish protein profiles in serum and nasal epithelial cells of cystic fibrosis individuals in comparison with controls, asthma and chronic obstructive pulmonary disease patients for specific biomarker signatures identification. DESIGN AND METHODS: Protein extracts were analyzed by Surface Enhanced Laser Desorption/Ionization Time-Of-Flight Mass-Spectrometry (SELDI-TOF-MS). RESULTS: The mass spectra revealed a set of peaks with differential expression in serum and nasal cells among the different groups studied, resulting into peak signatures representative/specific of each pathology. Logistic regressions were applied to those peaks; sensitivity, specificity, Youden's indexes and area under the curve (AUC) of the respective receiver operating characteristic (ROC) curves were compared. DISCUSSION: Multivariate analysis demonstrated that combination of peaks has a better predictive value than the individual ones. These protein signatures may serve as diagnostic/prognostic markers for the studied diseases with common clinical features, or as follow-up assessment markers of therapeutic interventions.
- Serum proteomics signature of Cystic Fibrosis patients: A complementary 2-DE and LC–MS/MS approachPublication . Charro, Nuno; Hood, Brian L.; Faria, Daniel; Pacheco, Paula; Azevedo, Pilar; Lopes, Carlos; Bugalho de Almeida, António; Couto, Francisco M.; Conrads, Thomas P.; Penque, DeborahComplementary 2D-PAGE and ‘shotgun’ LC–MS/MS approaches were combined to identify medium and low-abundant proteins in sera of Cystic Fibrosis (CF) patients (mild or severe pulmonary disease) in comparison with healthy CF-carrier and non-CF carrier individuals aiming to gain deeper insights into the pathogenesis of this multifactorial genetic disease. 78 differentially expressed spots were identified from 2D-PAGE proteome profiling yielding 28 identifications and postulating the existence of post-translation modifications (PTM). The ‘shotgun’ approach highlighted altered levels of proteins actively involved in CF: abnormal tissue/airway remodeling, protease/antiprotease imbalance, innate immune dysfunction, chronic inflammation, nutritional imbalance and Pseudomonas aeruginosa colonization. Members of the apolipoproteins family (VDBP, ApoA-I, and ApoB) presented gradually lower expression from non-CF to CF-carrier individuals and from those to CF patients, results validated by an independent assay. The multifunctional enzyme NDKB was identified only in the CF group and independently validated by WB. Its functions account for ion sensor in epithelial cells, pancreatic secretion, neutrophil-mediated inflammation and energy production, highlighting its physiological significance in the context of CF. Complementary proteomics-based approaches are reliable tools to reveal pathways and circulating proteins actively involved in a heterogeneous disease such as CF.