Browsing by Author "Laffon, Blanca"
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- Adequacy of the standardised in vitro mammalian cell Micronucleus (MN) test for nanomaterials genotoxicity testingPublication . Fernández-Bertólez, Natalia; Rodríguez-Fernández, R.; Lema-Arranz, C.; Pásaro, E.; Brandão, Fátima; Teixeira, João Paulo; Costa, Carla; Valdiglesias, Vanessa; Laffon, BlancaAbout adequacy of the standardised in vitro mammalian cell Micronucleus (MN) test for nanomaterials genotoxicity testing.
- Analysis of cellular damage induced by silica-coated iron oxide nanoparticles on neuronal cellsPublication . Laffon, Blanca; Kiliç, G.; Fernandez Bertólez, N.; Costa, C.; Costa, S.; Teixeira, J.P.; Pásaro, E.; Valdiglesias, V.The objective of this work was to evaluate toxicity induced by silica-coated ION on a human neuronal cell line (SHSY5Y).
- Applicability of EU(7)-PIM criteria in cross-national studies in European countriesPublication . Fialová, Daniela; Brkić, Jovana; Laffon, Blanca; Reissigová, Jindra; Grešáková, Silvia; Dogan, Soner; Doro, Peter; Tasić, Ljiljana; Marinković, Valentina; Valdiglesias, Vanessa; Costa, Solange; Kostřiba, JanBackground: The European Union (EU)(7)-PIM (potentially inappropriate medication) list presents the most comprehensive and up-to-date tool for evaluation of PIM prescribing in Europe; however, several country-specific studies have documented lower specificity of this list on pharmaceutical markets of some countries. The aim of our study was to describe approval rates and marketing of PIMs stated by EU(7)-PIM criteria in six EU countries [in comparison with the American Geriatric Society (AGS) Beers 2015 criteria]. Methods: Research teams of six EU countries (Czech Republic, Spain, Portugal, Serbia, Hungary and Turkey) participated in this study conducted by WG1b EU COST Action IS1402 group in the period October 2015-November 2018. Data on approval rates of PIMs and their availability on pharmaceutical markets have been obtained from databases of national drug-regulatory institutes and up-to-date drug compendia. The EU(7)-PIM list and AGS Beers 2015 Criteria (Section 1) were applied. Results: PIMs from EU(7)-PIM list were approved for clinical use more often than those from the AGS Beers 2015 criteria (Section 1). Approval rates for EU(7)-PIMs ranged from 42.8% in Serbia to 71.4% in Spain (for AGS criteria only from 36.4% to 65.1%, respectively). Higher percentages of approved PIMs were documented in Spain (71.4%), Portugal (67.1%) and Turkey (67.5%), lower in Hungary (55.5%), Czech Republic (50.2%) and Serbia (42.8%). The majority of approved PIMs were also currently marketed in all countries except in Turkey (19.8-21.7% not marketed PIMs) and less than 20% of PIMs were available as over-the-counter medications (except in Turkey, 46.4-48.1%). Conclusions: The EU(7)-PIM list was created for utilization in European studies; however, applicability of this list is still limited in some countries, particularly in Eastern and Central Europe. The EU project EUROAGEISM H2020 (2017-2021) that focuses on PIM prescribing and regulatory measures in Central and Eastern European countries must consider these limits.
- Are iron oxide nanoparticles safe? Current knowledge and future perspectivesPublication . Valdiglesias, Vanessa; Fernández-Bertólez, Natalia; Kiliç, Gözde; Costa, Carla; Costa, Solange; Fraga, Sonia; Bessa, Maria Joao; Pásaro, Eduardo; Teixeira, João Paulo; Laffon, BlancaDue to their unique physicochemical properties, including superparamagnetism, iron oxide nanoparticles (ION) have a number of interesting applications, especially in the biomedical field, that make them one of the most fascinating nanomaterials. They are used as contrast agents for magnetic resonance imaging, in targeted drug delivery, and for induced hyperthermia cancer treatments. Together with these valuable uses, concerns regarding the onset of unexpected adverse health effects following exposure have been also raised. Nevertheless, despite the numerous ION purposes being explored, currently available information on their potential toxicity is still scarce and controversial data have been reported. Although ION have traditionally been considered as biocompatible - mainly on the basis of viability tests results - influence of nanoparticle surface coating, size, or dose, and of other experimental factors such as treatment time or cell type, has been demonstrated to be important for ION in vitro toxicity manifestation. In vivo studies have shown distribution of ION to different tissues and organs, including brain after passing the blood-brain barrier; nevertheless results from acute toxicity, genotoxicity, immunotoxicity, neurotoxicity and reproductive toxicity investigations in different animal models do not provide a clear overview on ION safety yet, and epidemiological studies are almost inexistent. Much work has still to be done to fully understand how these nanomaterials interact with cellular systems and what, if any, potential adverse health consequences can derive from ION exposure.
- Assessing the in vitro toxicity of airborne (nano)particles to the human respiratory system: from basic to advanced modelsPublication . Bessa, Maria João; Brandão, Fátima; Rosário, Fernanda; Moreira, Luciana; Reis, Ana Teresa; Valdiglesias, Vanessa; Laffon, Blanca; Fraga, Sónia; Teixeira, João PauloSeveral studies have been conducted to address the potential adverse health risks attributed to exposure to nanoscale materials. While in vivo studies are fundamental for identifying the relation-ship between dose and occurrence of adverse effects, in vitro model systems provide important information regarding the mechanism(s) of action at the molecular level. With a special focus on exposure to inhaled (nano)particulate material toxicity assessment, this review provides an over-view of the available human respiratory models and exposure systems for in vitro testing, advan-tages, limitations, and existing investigations using models of different complexity. A brief overview of the human respiratory system, pathway and fate of inhaled (nano)particles is also presented.
- Assessment of genotoxic effects of titanium dioxide nanoparticles on different human cell typesPublication . Fernández-Bertólez, Natalia; Brandao, Fátima; Rosário, Fernanda; Bessa, Maria João; Fraga, Sónia; Pásaro, Eduardo; Teixeira, Joao Paulo; Costa, Carla; Laffon, Blanca; Vanessa, ValdiglesiasThe main objective of the present work was to assess the cellular uptake and potential genotoxicity (micronuclei induction) of TiO2 NPs on four diverse human cell lines.
- Assessment of immunotoxicity parameters in individuals occupationally exposed to leadPublication . García-Lestón, Julia; Roma-Torres, Joana; Mayan, Olga; Schroecksnadel, Sebastian; Fuchs, Dietmar; Moreira, Ana; Pásaro, Eduardo; Méndez, Josefina; Teixeira, João Paulo; Laffon, BlancaAlthough adverse health effects produced by lead (Pb) have long been recognized, studies regarding the immunotoxic effects of occupational exposure report conflicting results. In a previous study, alterations in some immunological parameters were noted in 70 Pb-exposed workers. In view of these results, it was of interest to extend this study comprising a larger population and increasing the number of immunological endpoints assessed. Accordingly, in this study the immunotoxic effects of occupational exposure to Pb were assessed by analyzing (1) percentages of lymphocyte subsets (CD3⁺, CD4⁺, CD8⁺, CD19⁺, and CD56⁺/16⁺); (2) concentration of plasma cytokines, namely, interleukin (IL) 2, IL4, IL6, IL10, tumor necrosis factor (TNF) α, and interferon (IFN) γ; and (3) plasma concentrations of neopterin, tryptophan (Trp), and kynurenine (Kyn). In addition, the possible influence of genetic polymorphisms in the vitamin D receptor (VDR) and δ-aminolevulinic acid dehydratase (ALAD) genes on immunotoxicity parameters was studied. Exposed workers showed significant decreases in %CD3⁺, %CD4⁺/%CD8⁺ ratio, IL4, TNFα, IFNγ, and Kyn to Trp ratio (Kyn/Trp), and significant increases in %CD8⁺, IL10, and Trp levels. All these parameters, except Trp, were significantly correlated with exposure biomarkers. No significant influence of genetic polymorphisms was observed. Significant correlation between Kyn/Trp and neopterin concentrations suggests an involvement of indoleamine 2,3-dioxygenase in the Trp metabolic alterations, which may contribute to some of the immune alterations observed. Results obtained suggest that occupational exposure to PB may influence the immune system by impairing several mechanisms, which might ultimately produce deregulation of the immune response and diminish immunosurveillance in exposed individuals.
- Assessment of oxidative damage induced by iron oxide nanoparticles on different nervous system cellsPublication . Fernández-Bertólez, Natalia; Costa, Carla; Bessa, Maria João; Park, Magriet; Carriere, Marie; Dussert, Fanny; Teixeira, João Paulo; Pásaro, Eduardo; Laffon, Blanca; Valdiglesias, VanessaIron oxide nanoparticles (ION) have received much attention for their utility in biomedical applications, such as magnetic resonance imaging, drug delivery and hyperthermia, but concerns regarding their potential harmful effects are also growing. Even though ION may induce different toxic effects in a wide variety of cell types and animal systems, there is a notable lack of toxicological data on the human nervous system, particularly important given the increasing number of applications on this specific system. An important mechanism of nanotoxicity is reactive oxygen species (ROS) generation and oxidative stress. On this basis, the main objective of this work was to assess the oxidative potential of silica-coated (S-ION) and oleic acid-coated (O-ION) ION on human SH-SY5Y neuronal and A172 glial cells. To this aim, ability of ION to generate ROS (both in the absence and presence of cells) was determined, and consequences of oxidative potential were assessed (i) on DNA by means of the 8-oxo-7,8-dihydroguanine DNA glycosylase (OGG1)-modified comet assay, and (ii) on antioxidant reserves by analyzing ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG). Conditions tested included a range of concentrations, two exposure times (3 and 24 h), and absence and presence of serum in the cell culture media. Results confirmed that, even though ION were not able to produce ROS in acellular environments, ROS formation was increased in the neuronal and glial cells by ION exposure, and was parallel to induction of oxidative DNA damage and, only in the case of neuronal cells treated with S-ION, to decreases in the GSH/GSSG ratio. Present findings suggest the production of oxidative stress as a potential action mechanism leading to the previously reported cellular effects, and indicate that ION may pose a health risk to human nervous system cells by generating oxidative stress, and thus should be used with caution.
- Association of inflammatory mediators with frailty status in older adults: results from a systematic review and meta-analysisPublication . Marcos-Pérez, Diego; Sánchez-Flores, María; Proietti, Stefania; Bonassi, Stefano; Costa, Solange; Teixeira, Joao Paulo; Fernández-Tajes, Juan; Pásaro, Eduardo; Laffon, Blanca; Valdiglesias, VanessaFrailty is a geriatric syndrome defined as a status of extreme vulnerability to stressors, leading to a higher risk of negative health-related outcomes. "Inflammaging", an age-related state of low-grade chronic inflammation, is characterized by an increased concentration of pro-inflammatory cytokines and acute phase proteins. Inflammaging has been postulated as an underlying mechanism of frailty, and several studies tested the relationship between frailty and concentration of inflammatory mediators. The aim of this systematic review and meta-analysis was to test whether inflammatory mediators are overproduced in frail older adults. Among the 758 articles identified in the literature search, 50 were included in the systematic review, and 39 in the three meta-analyses, i.e., C-reactive protein (CRP), interleukin 6 (IL6), and tumor necrosis factor α. To reduce heterogeneity, meta-analyses were restricted to studies identifying frailty by the Fried et al. [1] [J. Gerontol. A. Biol. Sci. Med. Sci. 56, M146-56] phenotypic criteria. Quantitative analyses measuring the association between frailty and biomarker concentrations showed significant differences when frail subjects were compared to non-frail and pre-frail subjects for CRP and IL6. This work established strong association between inflammatory biomarkers and frailty, confirming the role of age-related chronic inflammation in frailty development.
- Avaliação in vitro da neurotoxicidade de nanopartículas de magnetite revestidas por sílicaPublication . Costa, Carla; Brandão, Fátima; Kiliç, Gözde; Fernández-Bertólez, Natalia; Bessa, M. João; Costa, Solange; Valdiglesias, Vanessa; Laffon, Blanca; Teixeira, João Paulo