Percorrer por autor "Méndez, Josefina"
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- 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.
- Genotoxic effects of occupational exposure to lead and influence of polymorphisms in genes involved in lead toxicokinetics and in DNA repairPublication . García-Lestón, Julia; Roma-Torres, Joana; Vilares, Maria; Pinto, Rui; Prista, João; Teixeira, João Paulo; Mayan, Olga; Conde, Joao; Pingarilho, Marte; Gaspar, Jorge Francisco; Pásaro, Eduardo; Méndez, Josefina; Laffon, BlancaLead is still widely used in many industrial processes and is very persistent in the environment. Although toxic effects caused by occupational exposure to lead have been extensively studied, there are still conflicting results regarding its genotoxicity. In a previous pilot study we observed some genotoxic effects in a population of lead exposed workers. Thus, we extended our study analysing a larger population, increasing the number of genotoxicity endpoints, and including a set of 20 genetic polymorphisms related to lead toxicokinetics and DNA repair as susceptibility biomarkers. Our population comprised 148 workers from two Portuguese factories and 107 controls. The parameters analysed were: blood lead levels (BLL) and δ-aminolevulinic acid dehydratase (ALAD) activity as exposure biomarkers, and T-cell receptor (TCR) mutation assay, micronucleus (MN) test, comet assay and OGG1-modified comet assay as genotoxicity biomarkers. Lead exposed workers showed markedly higher BLL and lower ALAD activity than the controls, and significant increases of TCR mutation frequency (TCR-Mf), MN rate and DNA damage. Oxidative damage did not experience any significant alteration in the exposed population. Besides, significant influence was observed for VDR rs1544410 polymorphism on BLL; APE1 rs1130409 and LIG4 rs1805388 polymorphisms on TCR-Mf; MUTYH rs3219489, XRCC4 rs28360135 and LIG4 rs1805388 polymorphisms on comet assay parameter; and OGG1 rs1052133 and XRCC4 rs28360135 polymorphisms on oxidative damage. Our results showed genotoxic effects related to occupational lead exposure to levels under the Portuguese regulation limit of 70 μg/dl. Moreover, a significant influence of polymorphisms in genes involved in DNA repair on genotoxicity biomarkers was observed.
- Neuron and Glial Cells Exposed to Cerium Dioxide Nanoparticles: Results from MTT and γH2AX AssaysPublication . Fernández-Bertólez, Natalia; Touzani, Assia; Martínez, Luisa; Méndez, Josefina; Reis, Ana Teresa; Costa, Carla; Fraga, Sonia; Teixeira, João Paulo; Pásaro, Eduardo; Laffon, Blanca; Valdiglesias, VanessaCerium dioxide nanoparticles (CeO2NP) show antioxidant enzyme-like properties and reactive oxygen species (ROS) scavenging activity, making them a promising material for potential therapeutic applications in neurodegenerative diseases. The objective of this work was to assess the biological behavior of CeO2NP in human SH-SY5Y neuronal and A172 glial cells by means of the MTT assay and the γH2AX assay. Despite the significant dose- and time-dependent NP internalization by both cell lines, nanoceria generally presented scarce cytotoxicity or genotoxicity, essentially restricted to the highest NP doses and longest exposure times. In conclusion, a high biocompatibility of CeO2NP was observed under the conditions tested.
- Viral genetics and transmission dynamics in the second wave of mpox outbreak in Portugal and forecasting public health scenariosPublication . Cordeiro, Rita; Caetano, Constantino P.; Sobral, Daniel; Ferreira, Rita; Coelho, Luís; Pelerito, Ana; de Carvalho, Isabel Lopes; Namorado, Sónia; Loyens, Dinis B.; Mexia, Ricardo; Fernandes, Cândida; Neves, José Miguel; João, Ana Luísa; Rocha, Miguel; Duque, Luís Miguel; Correia, Inês; Baptista, Teresa; Brazão, Cláudia; Sousa, Diogo; Filipe, Paulo; Alpalhão, Miguel; Maltez, Fernando; Póvoas, Diana; Pinto, Raquel; Caria, João; Patrocínio de Jesus, Rita; Pacheco, Patrícia; Peruzzu, Francesca; Méndez, Josefina; Ferreira, Luís; Mansinho, Kamal; Alves, João Vaz; Vasconcelos, Joana; Domingos, João; Casanova, Sara; Duarte, Frederico; Gonçalves, Maria João; Salvador, Mafalda Brito; Guimarães, Mafalda Andresen; Martins, Sueila; Oliveira, Marvin Silva; Santos, Daniela; Vieira, Luís; Núncio, Maria Sofia; Borges, Vítor; Gomes, João PauloIn 2023, a second wave of the global mpox epidemic, which is mainly affecting men who have sex with men (MSM), was observed in some countries. Herein, we benefited from a large viral sequence sampling (76/121; 63%) and vast epidemiological data to characterise the re-emergence and circulation of the (MPXV) in Portugal during 2023. We also modelled transmission and forecasted public health scenarios through a compartmental susceptible-exposed-infectious-recovered (SEIR) model. Our results suggest that the 2023 mpox wave in Portugal resulted from limited introduction(s) of MPXV belonging to C.1.1 sublineage, hypothetically from Asia, followed by sustained viral transmission and potential exportation to other countries. We estimated that the contribution of the MSM high sexual activity group to mpox transmission was 120 (95% CrI: 30-3553) times higher than that of the low sexual activity group. However, among the high sexual activity group, vaccinated individuals likely contributed approximately eight times less [0.123 (95% CrI: 0.068-0.208)] than the unvaccinated ones. Vaccination was also linked to potential reduced disease severity, with a Mpox Severity Score of 6.0 in the vaccinated group compared to 7.0 in unvaccinated individuals. Scenario analysis indicated that transmission is highly sensitive to sexual behaviour, projecting that a slight increase in the MSM sub-population with high sexual activity can trigger new mpox waves. This study strongly supports that continued vaccination, targeted awareness among risk groups and routine genomic epidemiology is needed to anticipate and respond to novel MPXV threats (e.g. global dissemination of clade I viruses).