Percorrer por autor "Lavinha, João"
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- 1º Workshop sobre Biomonitorização Humana em Portugal: síntese do encontroPublication . Silva, Maria João; Lavinha, JoãoRealizou-se no passado dia 11 de maio de 2018 o 1st HBM-PT, tendo reunido no Instituto Nacional de Saúde Doutor Ricardo Jorge (INSA), em Lisboa, mais de oitenta participantes da Academia, Indústria, Saúde Ocupacional e Regulamentação, entre outros. O Encontro partiu da iniciativa do conjunto de parceiros que constituem o denominado National Hub (NH-PT) para o projeto “Human Biomonitoring Initiative - HBM4EU” que inclui a Fundação para a Ciência e a Tecnologia, I.P. (FCT), Instituto Nacional de Saúde Dr. Ricardo Jorge, I.P. (INSA), Direção Geral da Saúde (DGS) e Agência Portuguesa do Ambiente, I.P. (APA), em colaboração com a Faculdade de Medicina, Universidade de Lisboa (FMUL) e Escola Superior de Tecnologia da Saúde Lisboa (ESTeSL), Instituto Politécnico de Lisboa. Este primeiro Workshop visou juntar investigadores reguladores, público em geral e outros atores-chave para discutir a contribuição da biomonitorização humana para as políticas de saúde e ambiente e para a avaliação de risco para a saúde humana. Para além disso, pretendeu informar as partes interessadas acerca do projeto HBM4EU, incluindo aspetos relevantes, tais como a sua estrutura e as atividades já desenvolvidas durante o primeiro ano do projeto ou a desenvolver futuramente. Nesta síntese os autores pretenderam oferecer uma visão geral do evento, através de um breve resumo das apresentações dos oradores convidados e dos temas abordados pelo painel de discussão tecendo ainda algumas considerações finais sobre o evento.
- 2-DIGE of Red Blood Cells from Sickle-Cell Disease Patients with Severe Vaso-Occlusion.Publication . Vaz, Fátima; Charro, Nuno; Morais, Anabela; Lavinha, João; Penque, Deborah
- Alpha-thalassemia due to novel deletions and complex rearrangements in the subtelomeric region of chromosome 16pPublication . Ferrão, José; Silva, Marisa; Gonçalves, Lúcia; Gomes, Susana; Loureiro, Pedro; Coelho, Andreia; Miranda, Armandina; Seuanes, Filomena; Batalha Reis, Ana; Pina, Francisca; Maia, Raquel; Kjollerstrom, Paula; Monteiro, Estela; F. Lacerda, João; Lavinha, João; Gonçalves, João; Faustino, PaulaIntroduction: Inherited deletions removing the α-globin genes and/or their upstream regulatory elements (MCSs) give rise to alpha-thalassemia, one of the most common genetic recessive disorders worldwide. The pathology is characterized by microcytic hypochromic anemia due to reduction of the α-globin chain synthesis, which are essential for hemoglobin tetramerization. Material and Methods: In order to clarify the suggestive α-thalassemia phenotype in eleven patients, we performed Multiplex Ligation-dependent Probe Amplification with commercial and synthetic engineered probes, gap-PCR, and Sanger sequencing to search for deletions in the subtelomeric region of chromosome 16p. Results: We have identified five distinct large deletions, two of them novel, and one indel. The deletions range from approximately 3.3 to 323 kb, and i) remove the whole α-globin cluster; or ii) remove exclusively the upstream regulatory elements leaving the α-globin genes structurally intact. The indel consists in the loss of MCS-R2 (HS-40), which is the most important distal regulatory element for the α-globin gene expression, and the insertion of 39 bp, seemingly resulting from a complex rearrangement involving two DNA segments (probably from chromosome 3q) bridging the deletion breakpoints with a CC-bp orphan sequence in between. Finally, in one patient no α-globin deletion or point mutation were found. This patient revealed to be a very unusual case of acquired alpha-thalassemia associated with a myelodysplastic syndrome. Conclusions: Our study widens the spectrum of molecular lesions by which α-thalassemia may occur and emphasizes the importance of diagnosing large α-zero-deletions to provide patients with appropriate genetic counseling.
- Alpha-thalassemia due to novel deletions and complex rearrangements in the subtelomeric region of chromosome 16pPublication . Ferrão, José; Silva, Marisa; Gonçalves, Lúcia; Gomes, Susana; Loureiro, Pedro; Coelho, Andreia; Miranda, Armandina; Seuanes, Filomena; Batalha Reis, Ana; Valtonen-André, Camila; Sonesson, Annika; Pina, Francisca; Maia, Raquel; Kjollerstrom, Paula; Monteiro, Estela; F. Lacerda, João; Lavinha, João; Gonçalves, João; Faustino, PaulaIntroduction: Inherited deletions removing the α-globin genes and/or their upstream regulatory elements (MCSs) give rise to alpha-thalassemia, one of the most common genetic recessive disorders worldwide. The pathology is characterized by microcytic hypochromic anemia due to reduction of the α-globin chain synthesis, which are essential for hemoglobin tetramerization. Material and Methods: In order to clarify the suggestive α-thalassemia phenotype in eleven patients, we performed Multiplex Ligation-dependent Probe Amplification with commercial and synthetic probes, gap-PCR, and Sanger sequencing to search for deletions in the subtelomeric region of chromosome 16p. Results: We have identified six distinct large deletions, three of them novel, and one indel. The deletions range from approximately 3.3 to 323 kb, and i) remove the whole α-globin cluster; or ii) remove exclusively the upstream regulatory elements leaving the α-globin genes structurally intact. The indel consists in the loss of MCS-R2 (HS-40), which is the most important distal regulatory element for the α-globin gene expression, and the insertion of 39 nt, seemingly resulting from a complex rearrangement involving two DNA segments (probably from chromosome 3q), bridging the deletion breakpoints with a CC-bp orphan sequence in between. Finally, in one patient no α-globin deletion or point mutation were found. This patient revealed to have acquired alpha-thalassemia associated with a myelodysplastic syndrome. Conclusions: Our study widens the spectrum of molecular lesions by which α-thalassemia may occur and emphasizes the importance of diagnosing large α0-deletions to provide patients with appropriate genetic counseling.
- Anemia in preschool children from Angola: a review of the evidencePublication . Fançony, Cláudia; Lavinha, João; Brito, Miguel; Barros, HenriqueAngola is one of the southern African countries with the highest prevalence of anemia, and despite the high geographic heterogeneity of its distribution across the country, it was reported to be indicative of a severe public health problem in some areas, mainly in children. Despite the relevance of this condition in the country there is still an important gap regarding scientific evidences and knowledge systematization in the indexed literature, that could be used to inform and optimize national public health policies willing to address it. Furthermore, the changes in anemia epidemiology among African preschool children and the late updates in nutrition-specific and nutrition-sensitive preventive strategies in the continent are of imperative relevance, as they could contribute to design context-specific national approaches to reduce anemia's morbidity and mortality. In this study we intent to perform a systematic review regarding the sparse evidence available on the country regarding the prevalence of anemia, its associated factors, the prevention, and/or control strategies with potential to reduce anemia that were implemented, and to discuss interventions targeting infections and/or nutrition conducted in other African countries.
- Aplicação de scores de gravidade à anemia das células falciformes: um problema ainda por resolverPublication . Coelho, Andreia; Dias, Alexandra; Morais, Anabela; Nunes, Baltazar; Faustino, Paula; Lavinha, João
- Are standard genotoxicity tests useful for the safety evaluation of nanomaterials?Publication . Louro, Henriqueta; Tavares, Ana; Vital, Nádia; Antunes, Susana; Costa, Pedro; Alverca, Elsa; Lavinha, João; Silva, Maria JoãoNanomaterials (NMs) are widely used in a diversity of consumer products, despite uncertainties surrounding the potential health risks that they pose to humans and the environment. One of the major concerns is the potential to induce cancer. To analyze in a short term the carcinogenic properties of a compound, genotoxicity assays in mammalian cell lines or animal models are frequently used. In the context of an EU Joint Action, in the present work we have used standard genotoxicity assays (comet, micronucleus and mutation assays) to investigate the effects associated with the exposure to titanium dioxide nanomaterials (TiO2), following standardized dispersion and assay procedures, in three types of human cells and in a mouse model. The results showed slight but significant increases in the frequencies of micronuclei after exposure to some of the NMs, as compared to controls. No clear dose-response relationships could be disclosed. One of the tested TiO2 yielded equivocal results in vitro micronucleus assay and was positive in the comet assay in pulmonary cells. In view of the inconclusive results,it was further analyzed in vivo, using the lacZ transgenic mouse model. It did not induce genotoxic effects in mice, 28 days after injection, despite the accumulation of the NM observed in the mouse liver. Regarding safety assessment, the different genotoxicity observed for closely related NMs, but that differ in some physicochemical characteristics, highlights the importance of investigating the toxic potential of each NM individually, instead of assuming a common mechanism and equal genotoxic effects for a set of similar NMs. The equivocal genotoxicity of the nanosized TiO2 in human cells in vitro was not confirmed in vivo, and therefore the predictive value of these in vitro tests for identifying genotoxic (and potentially carcinogenic) NMs in vivo should be clarified, before extrapolating the conclusions for human health.
- Assessment of the genotoxicity of a titanium dioxide nanomaterial using a combination of in vitro and in vivo assaysPublication . Tavares, Ana; Louro, Henriqueta; Vital, Nádia; Antunes, Susana; Lavinha, João; Silva, Maria JoãoHuman exposure to manufactured nanomaterials such as titanium dioxide (TiO2), often used in sunscreens and cosmetics, has increased worldwide. Their specific properties, such as size and high surface area/mass, render them attractive for many applications, but may also be associated to higher toxicity in biological systems and adverse effects in humans. In the context of EU Joint Action NANOGENOTOX (www.nanogenotox.com), the present work aimed to analyse the potential genotoxic effects of a well-characterized TiO2 nanomaterial, correlating in vitro and in vivo effects. TiO2 dispersions were prepared according to a standardized protocol and were used for exposure of human cells (in vitro) or mice (in vivo). The cytokinesis-block micronucleus assay (OECD guideline 487) was performed in human bronchial epithelial cells (BEAS-2B) and primary cultures of human lymphocytes. Additionally, Comet assay was conducted in BEAS-2B cells. In vivo testing was carried out on a mouse model after exposure of groups of mice intravenously. The mammalian erythrocyte micronucleus test in mouse blood (OECD guideline 474) and comet assay in mouse organs were performed. Concurrent positive chemical controls and a nanoparticle control (ZnO) were included. While the results obtained in BEAS-2B cells showed no induction of micronucleated cells, a significant increase was observed in human lymphocytes at the dose of 125 μg/ml. Exposure of BEAS-2B to TiO2 caused an increase in DNA damage detected by comet assay (3-fold increase, p< 0.006) although no dose-response effect was seen. In mice, there was no genotoxicity in both assays. In summary, using a standardized preparation of nanomaterials, results obtained were mostly negative after TiO2 exposure, in both in vitro and in vivo assays. However, somewhat different genotoxicity outcomes may reflect tissue-specific effects affecting, e.g., cellular uptake of the nanomaterial.
- Avaliação da segurança de nanomateriais manufacturados através da caracterização do seu potencial efeito genotóxicoPublication . Silva, Maria João; Louro, Henriqueta; Lavinha, JoãoPresentemente, encontra-se já disponível uma nova geração de produtos inovadores contendo um amplo espectro de nanomateriais (NM), em áreas tão diversas como a biomedicina, electrónica, alimentação e cosmética. Porém, os potenciais riscos para a saúde humana decorrentes da exposição a estes produtos, desde a fase de produção e aplicação industrial até à manipulação e utilização pelo consumidor, são motivo de preocupação, à escala mundial. A potencial actividade carcinogénica dos NM, em particular, constitui uma séria preocupação que se parece justificar pelas observações de que à escala “nano” algumas substâncias revelam maior toxicidade em roedores do que os seus análogos não-ultrafinos e são tumorigénicas. Para avaliar de uma forma simplificada, rápida e económica a potencial carcinogenicidade de um composto, caracterizam-se os seus efeitos genotóxicos em sistemas celulares ou em roedores que se espera serem preditivos de um potencial efeito carcinogénico no homem. No que se refere à caracterização dos efeitos genotóxicos dos NM, uma questão crucial é saber em que medida os métodos/estratégias convencionais são aplicáveis a estes materiais, considerando que a sua entrada nas células, processamento e interacção com as moléculas biológicas podem conduzir a efeitos tóxicos imprevisíveis, ao nível do organismo. Tendo em vista a resposta a esta e outras questões, foi delineada e recentemente aprovada a Acção Concertada Europeia “NANOGENOTOX – Safety evaluation of manufactured nanomaterials by characterisation of their potential genotoxic hazard”, que decorrerá entre 2010 e 2013. Serão apresentados os objectivos e o estado actual dos estudos no âmbito desse projecto que visa, essencialmente, o estabelecimento de metodologias robustas para avaliar a potencial genotoxicidade de três classes de nanopartículas (sílica, titânio e nanotubos de carbono), de forma a contribuir para a avaliação de risco decorrente da exposição a esses NM. De entre os objectivos específicos do NANOGENOTOX, salentam-se: i) a caracterização das propriedades físico-químicas dos NM; ii) a avaliação dos efeitos genotóxicos através do ensaio do cometa e da análise de micronúcleos in vitro e in vivo e iii) a determinação de parâmetros toxicocinéticos dos NM num modelo murino. Espera-se que os resultados gerados ao longo do projecto permitam reforçar, expandir e partilhar o conhecimento requerido para uma avaliação global do risco das nanopartículas e permitam ainda estabelecer uma estratégia capaz de gerar dados relevantes e fidedignos sobre a segurança dos nanomateriais, utilizável pelas autoridades de saúde pública a nível europeu.
- Avaliação do potencial citotóxico e genotóxico de contaminantes de sedimentos do Estuário do Sado numa linha celular humanaPublication . Pinto, Miguel; Costa, Pedro Manuel; Louro, Henriqueta; Costa, Maria Helena; Lavinha, João; Caeiro, Sandra; Silva, Maria JoãoO presente estudo integra-se num projeto mais amplo que visa avaliar o risco ambiental – que inclui os riscos ecológicos e para a saúde humana - associado a este ambiente estuarino contaminado. Em particular, este estudo teve como objetivo caracterizar o potencial citotóxico e genotóxico de sedimentos colhidos em vários locais de pesca do Estuário do Sado numa linha celular humana, tendo em vista uma avaliação de eventuais efeitos nefastos para a saúde humana.