Browsing by Author "Silva, Maria João"
Now showing 1 - 10 of 348
Results Per Page
Sort Options
- 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.
- Abordagens experimentais à avaliação do efeito genotóxico de agentes químicos e físicosPublication . Silva, Maria João; Louro, HenriquetaAula 2: Abordagens experimentais à avaliação do efeito genotóxico de agentes químicos e físicos: Ensaios de longo-termo em roedores; Ensaios de curto-termo para avaliação de efeitos genotóxicos in vitro e in vivo; Linhas orientadoras para produtos farmacêuticos (ICH guidelines)
- Activation of RAC1/PAK1 axis potentiates transcriptional upregulation of DNA damage response genes via the BCL6/STAT5 switchPublication . Barros, Patrícia; Amaral, Andreia; Abrantes, Leonor; Oliveira, Tiago; Lourio, Henriqueta; Silva, Maria João; Jordan, Peter; Gama-Carvalho, Margarida; Matos, PauloColorectal cancer is one of the most prevalent types of cancer worldwide. The GTPase RAC1 and its effector PAK1 have been found overexpressed or hyperactivated in colorectal cancers, particularly those with more aggressive and invasive features, leading to unfavourable clinical prognosis, often resulting from chemoresistance.
- AD6.2 WP6 - Sustainability and capacity building. Results of the interaction and surveys with the Environment Protection Agency network and the National Reference Centre on Environment & HealthPublication . Lobo Vicente, Joana; Katsonouri, Andromachi; Hans, Reynders; Campenhout, Karen Van; Tarroja, Elena; Louro, Henriqueta; Isidro, Glória; Silva, Maria João; Bourqui, Martine; von Goetz, NatalieThe aim of this additional deliverable is to analyse the result of the interaction and surveys with the Environment Protection Agency network and the National Reference Centre on Environment & Health. The consultation to both the EPA network and the NRCs was done through a similar targeted survey, with the aim of understanding their perception of the current HBM4EU and their ideas for a future Human Biomonitoring initiative. The online survey also explored if and how their institution would use HBM4EU results in their work and it also explored the focus that their institution considered a future initiative might take. This could be in terms of exploring exposure to new emerging risks or understanding exposure to known chemical risks, such as heavy metals. In addition, it explored interest in participating in a new initiative and openness towards sharing of best practice. This included questions regarding the possible role that the EPAs and NRCs might play in such an initiative. The invitation was sent out to 29 EPA countries and 15 NRCs, from which 19 answers were obtained in total with 4 EPAs answered and 13 NRCs. One of the EPAs is also a HBM4EU partner, whereas from the 15 NRCs, 13 of those provided their countries/institution from which 7 are HBM4EU partners. The survey produced quite interesting results, where it was pointed out that HBM is the only instrument that can assess human exposure in an integrated and reliable way. From the institutions that are not part of HBM4EU, most of them were aware of the project. The ones that were already part of it would like to carry on as such if a future initiative is to take place. Despite the fact that a slightly higher percentage of institutions do not use HBM at the moment in their work (53 % vs 47 %), all of the institutions recognised the value of HBM and plan on using it in the future. All the NRCs and 75 % of the EPAs are interested in being part of a future initiative with a possible role in: positioning Human Biomonitoring in the strategic agenda of implementation of environmental policy and state of the environment in Europe, supporting the activities of the HBM initiative through an existing interest group under the NRC Network, creating joint working initiatives with other relevant networks. It was clear from the answers given that HBM has triggered an interest and there is a willingness to be part of the future initiative.
- Adverse Outcome Pathways Associated with the Ingestion of Titanium Dioxide Nanoparticles - A Systematic ReviewPublication . Rolo, Dora; Assunção, Ricardo; Ventura, Célia; Alvito, Paula; Gonçalves, Lídia; Martins, Carla; Bettencourt, Ana; Jordan, Peter; Vital, Nádia; Pereira, Joana; Pinto, Fátima; Matos, Paulo; Silva, Maria João; Louro, HenriquetaTitanium dioxide nanoparticles (TiO2-NPs) are widely used, and humans are exposed through food (E171), cosmetics (e.g., toothpaste), and pharmaceuticals. The oral and gastrointestinal (GIT) tract are the first contact sites, but it may be systemically distributed. However, a robust adverse outcome pathway (AOP) has not been developed upon GIT exposure to TiO2-NPs. The aim of this review was to provide an integrative analysis of the published data on cellular and molecular mechanisms triggered after the ingestion of TiO2-NPs, proposing plausible AOPs that may drive policy decisions. A systematic review according to Prisma Methodology was performed in three databases of peer-reviewed literature: Pubmed, Scopus, and Web of Science. A total of 787 records were identified, screened in title/abstract, being 185 used for data extraction. The main endpoints identified were oxidative stress, cytotoxicity/apoptosis/cell death, inflammation, cellular and systemic uptake, genotoxicity, and carcinogenicity. From the results, AOPs were proposed where colorectal cancer, liver injury, reproductive toxicity, cardiac and kidney damage, as well as hematological effects stand out as possible adverse outcomes. The recent transgenerational studies also point to concerns with regard to population effects. Overall, the findings further support a limitation of the use of TiO2-NPs in food, announced by the European Food Safety Authority (EFSA).
- Aflatoxins and ochratoxin A in baby foods and analysis of interactive cyto- and genotoxic effects in a human intestinal cell linePublication . Tavares, Ana; Alvito, Paula; Loureiro, Susana; Louro, Henriqueta; Silva, Maria JoãoMycotoxins are natural fungal metabolites and food contaminants with potential to cause severe acute and chronic conditions. Food contamination with mycotoxins such as aflatoxins (AF) and ochratoxin A (OTA) have been causing great concern, especially due to their potential mutagenic and carcinogenic effects. Children are especially vulnerable to the deleterious effects of these mycotoxins due to their physiological immaturity and high metabolic rate. Previous studies showed the co-occurrence of low concentrations of aflatoxins and OTA in baby foods. However, studies addressing potential interactive cyto- and genotoxic effects between these toxins are still scarce. In the present study we aimed to develop and validate a method for detection and quantification of total aflatoxins (B1, B2, G1, G2), AFM1 and OTA, and to evaluate the cytotoxic and genotoxic effects of mixtures of AFM1 and OTA, comparatively to their individual effects, in a human-derived intestinal cell line. A method based on immunoaffinity column cleanup and High Performance Liquid Chromatography with fluorescence detection (HPLC-FD), was applied and validated for total aflatoxins, AFM1 and OTA. The method was adequate for the analysis of these mycotoxins in baby foods and met the requirements of validation and quality control. The application of the method to a small set of baby foods marketed in Portugal showed an absence of quantifiable amounts of these mycotoxins. The individual and combined cytotoxic and genotoxic effects of AFM1 and OTA were characterized in Caco-2 cells using the Neutral Red and the Comet assays, respectively. A dose-dependent cytotoxicity was observed after individual exposure to OTA and AFM1, and the IC50 values were determined. The cytotoxic effect observed for several AFM1 and OTA mixtures was compared to the expected effect predicted by concentration addition (CA) and independent action (IA) conceptual models, using the MIXTOX model. A preliminary approach regarding the total data pool and considering the CA model as the most conservative model, pointed to an antagonistic cytotoxic effect caused by the mixture of both mycotoxins. However, a dose level deviation was observed after IA modelling, reflecting antagonism at low dose levels and synergism at higher dose levels. To better support data modelling, further cytotoxicity results from mixtures will be obtained and analyzed. To which respects the genotoxic effects, no induction of DNA damage was observed for the tested low doses, neither for individual toxins nor for their mixtures. The present study reinforces the relevance of exploring possible interactive adverse effects of mycotoxins that can contaminate foodstuff and thus having impact in human health. Future studies will face the challenge of understanding the mode of action of such mycotoxins when in mixture, in order to try predicting their effects.
- Ambiente, genoma e cancroPublication . Silva, Maria JoãoComunicação sobre factores ambientais e o impacto na saúde, nomeaamente relativo à exposição humana a agentes potencialmente mutagénicos e/ou carcinogénicos.
- An integrative assessment to determine the genotoxic hazard of estuarine sediments: combining cell and whole-organism responsesPublication . Costa, Pedro Manuel; Pinto, Miguel; Vicente, Ana M.; Gonçalves, Cátia; Rodrigo, Ana P.; Louro, Henriqueta; Costa, Maria Helena; Caeiro, Sandra; Silva, Maria JoãoThe application of the Comet assay in environmental monitoring remains challenging in face of the complexity of environmental stressors,e.g.,when dealing with estuarine sediments,that hampers the drawing of cause-effect relationships. Although the in vitro The application of the Comet assay in environmental monitoring remains challenging in face of the complexity of environmental stressors, e.g., when dealing with estuarine sediments, that hampers the drawing of cause-effect relationships. Although the in vitro Comet assay may circumvent confounding factors, its application in environmental risk assessment (ERA) still needs validation. As such, the present work aims at integrating genotoxicity and oxidative DNA damage induced by sediment-bound toxicants in HepG2 cells with oxidative stress-related effects observed in three species collected from an impacted estuary. Distinct patterns were observed in cells exposed to crude mixtures of sediment contaminants from the urban/industrial area comparatively to the ones from the rural/riverine area of the estuary, with respect to oxidative DNA damage and oxidative DNA damage. The extracts obtained with the most polar solvent and the crude extracts caused the most significant oxidative DNA damage in HepG2 cells, as measured by the formamidopyrimidine-DNA glycosylase (FPG)-modified Comet assay. This observation suggests that metals and unknown toxicants more hydrophilic than polycyclic aromatic hydrocarbons may be important causative agents, especially in samples from the rural part of the estuary, where oxidative DNA damage was the most significant. Clams, sole, and cuttlefish responded differentially to environmental agents triggering oxidative stress, albeit yielding results accordant with the oxidative DNA damage observed in HepG2 cells. Overall, the integration of in vivo biomarker responses and Comet assay data in HepG2 cells yielded a comparable pattern, indicating that the in vitro FPG-modified Comet assay may be an effective and complementary line-of-evidence in ERA even in particularly challenging, natural, scenarios such as estuarine environments.
- Analysis of the Characteristics and Cytotoxicity of Titanium Dioxide Nanomaterials Following Simulated In Vitro DigestionPublication . Bettencourt, Ana; Gonçalves, L.; Gramacho, A.; Vieira, A; Rolo, D.; Martins, Carla; Assunção, Ricardo; Alvito, Paula; Silva, Maria João; Louro, HenriquetaSeveral metallic nanomaterials (NMs), such as titanium dioxide nanomaterials (TiO2), present beneficial properties with a broad range of innovative applications. The human population is exposed to TiO2, particularly by ingestion, due to its increasing use as a food additive and inclusion in dietary supplements and food packaging materials. Whether this oral exposure may lead to adverse local or systemic outcomes has been the subject of research, but studies have generated contradictory results, reflecting differences in the physicochemical properties of the TiO2 studied, effects of the surrounding matrix, and modifications during digestion. This work aimed to investigate the toxic effects of three different TiO2 NMs (NM-103, NM-103 and NM-105) on the gastrointestinal tract cells, Caco-2 and HT29-MTX-E12, after the use of the standardized static INFOGEST 2.0 in vitro digestion method to mimic human digestion of TiO2, contributing to hazard assessment. The results show that, for one of the digested TiO2 NMs studied (NM-105), a more pronounced toxicity occurs after exposure of HT29-MTX-E12 intestinal cells, as compared to undigested NM, concomitantly with subtle changes in characteristics of the NM. Thus, the inclusion of the digestion simulation in the safety evaluation of ingested NMs through in vitro bioassays can better integrate the modifications that NMs suffer in the organism. It is expected that such an approach will reduce uncertainties in the hazard assessment of ingested NMs for human health.
- Analysis Of The Cytotoxicity And Genotoxicity of Digested Titanium Dioxide Nanomaterials (TiO2) In Intestinal CellsPublication . Louro, Henriqueta; Vieira, Adriana; Gramacho, Ana Catarina; Rolo, Dora; Vital, Nádia; Martins, Carla; Assunção, Ricardo; Alvito, Paula; Gonçalves, Lídia; Bettencourt, Ana Francisca; Silva, Maria JoãoTitanium dioxide nanomaterials (TiO2) have been frequently applied as food additives, in pharmaceuticals and in personal care products, such as toothpastes. Despite some regulators like EFSA concluded that the absorption of orally administered TiO2 is low, and that the use of TiO2 as a food additive does not raise a genotoxic concern, the presence of TiO2 in human organs was recently reported. This exposure may lead to adverse outcomes and has been poorly investigated. Furthermore, many of the biological effects of TiO2 described in the literature often overlook adequate physicochemical properties and their modification due to NMs interaction with the surrounding physiological matrices happening, e.g, during digestion. This work aimed to investigate in intestinal cells, the cyto- and genotoxic effects of TiO2 after the simulation of the human digestive process using the standardized INFOGEST in vitro digestion method, to better understand their potential negative impacts on the gastrointestinal tract. The TiO2 were characterized before and after digestion using DLS, zeta potential and TEM-EDS. The digestion product was used for cytotoxicity (MTT) and genotoxicity (comet, micronucleus) assays in two types of intestinal cells (Caco-2 and mucus secreting HT29-MTX cells). The results of the cytotoxicity and genotoxicity assays are discussed in view of the TiO2 secondary characteristics, to further understand the potential adverse intestinal outcomes in light of the transformation they suffer during digestion.