Esclerosis múltiple y cefaleas: aspectos clínicos, analíticos y radiológicos

La esclerosis múltiple es una enfermedad desmielinizante del sistema nervioso central que afecta a personas entre la segunda y tecera década de la vida, con impacto en la vida de los pacientes y que representa la primera cuausa de discapacidad no traumática en personas jóvenes. Por otro lado, las cefaleas y en concreto la migraña, son una de las quejas neurológicas más comunes. Suponen un gram impacto socio-económico en los sujetos que las padecen. Existen hipótesis que unen ambas patologías aunque los estudios al respecto son insuficientes todavía. Por ello, con la presente tesis se realizará un estudio analítico sobre una población de pacientes con esclerosis múltiple y cefaleas

Long-term effects of polystyrene nanoplastics in human intestinal Caco-2 cells

The increasing presence of micro- and nanoplastics (MNPLs) in the environment, and their consequent accumulation in trophic niches, could pose a potential health threat to humans, especially due to their chronic ingestion. In vitro studies using human cells are considered pertinent approaches to determine potential health risks to humans. Nevertheless, most of such studies have been conducted using short exposure times and high concentrations. Since human exposure to MNPLs is supposed to be chronic, there is a lack of information regarding the potential in vitro MNPLs effects under chronic exposure conditions. To this aim, we assessed the accumulation and potential outcomes of polystyrene nanoparticles (PSNPs), as a model of MNPLs, in undifferentiated Caco-2 cells (as models of cell target in ingestion exposures) under a relevant long-term exposure scenario, consisting of eight weeks of exposure to sub-toxic PSNPs concentrations. In such exposure conditions, culture-media was changed every 2-3 days to maintain constant exposure. The different analyzed endpoints were cytotoxicity, dysregulation of stress-related genes, genotoxicity, oxidative DNA damage, and intracellular ROS levels. These are endpoints that showed to be sensitive enough in different studies. The obtained results attest that PSNPs accumulate in the cells through time, inducing changes at the ultrastructural and molecular levels. Nevertheless, minor changes in the different evaluated genotoxicity-related biomarkers were observed. This would indicate that no DNA damage or oxidative stress is observed in the human intestinal Caco-2 cells after long-term exposure to PSNPs. This is the first study dealing with the long-term effects of PSNPs on human cultured cells

Harmful effects of true-to-life nanoplastics derived from PET water bottles in human alveolar macrophages

Altres ajuts: acords transformatius de la UABThe increasing presence of secondary micro/nanoplastics (MNPLs) in the environment requires knowing if they represent a real health concern. To such end, an important point is to test representative MNPLs such as the denominated true-to-life MNPLs, resulting from the degradation of plastic goods in lab conditions. In this study, we have used polyethylene terephthalate (PET) NPLs resulting from the degradation of PET water bottles. Since inhalation is an important exposure route to environmental MNPLS, we have used mouse alveolar macrophages (MH-S) as a target cell, and the study focused only on the cells that have internalized them. This type of approach is novel as it may capture the realistic adverse effects of PETNPLs only in the internalized cells, thereby mitigating any biases while assessing the risk of these MNPLs. Furthermore, the study utilized a set of biomarkers including intracellular reactive oxygen species (ROS) levels, variations on the mitochondrial membrane potential values, and the macrophage polarization to M1 (pro-inflammatory response) and M2 (anti-proinflammatory response) as possible cellular effects due to PETNPLs in only the cells that internalized PETNPLs. After exposures lasting for 3 and 24 h to a range of concentrations (0, 25, 50, and 100 μg/mL) the results indicate that no toxicity was induced despite the 100% internalization observed at the highest concentration. Significant intracellular levels of ROS were observed, mainly at exposures lasting for 24 h, in an indirect concentration-effect relationship. Interestingly, a reduction in the mitochondrial membrane potential was observed, but only at exposures lasting for 24 h, but without a clear concentration-effect relationship. Finally, PETNPL exposure shows a significant polarization from M0 to M1 and M2 subtypes. Polarization to M1 (pro-inflammatory stage) was more marked and occurred at both exposure times. Polarization to M2 (anti-inflammatory stage) was only observed after exposures lasting for 24 h. Due to the relevance of the described biomarkers, our results underscore the need for further research, to better understand the health implications associated with MNPL exposure

Micrornas as a suitable biomarker to detect the effects of long-term exposures to nanomaterials. Studies on tio2np and mwcnt

Altres ajuts: Universitat Autònoma de Barcelona PIF-UABThe presence of nanomaterials (NMs) in the environment may represent a serious risk to human health, especially in a scenario of chronic exposure. To evaluate the potential relationship between NM-induced epigenetic alterations and carcinogenesis, the present study analyzed a panel of 33 miRNAs related to the cell transformation process in BEAS-2B cells transformed by TiO2NP and long-term MWCNT exposure. Our battery revealed a large impact on miRNA expression profiling in cells exposed to both NMs. From this analysis, a small set of five miRNAs (miR-23a, miR-25, miR-96, miR-210, and miR-502) were identified as informative biomarkers of the transforming effects induced by NM exposures. The usefulness of this reduced miRNA battery was further vali-dated in other previously generated transformed cell systems by long-term exposure to other NMs (CoNP, ZnONP, MSiNP, and CeO2NP). Interestingly, the five selected miRNAs were consistently overexpressed in all cell lines and NMs tested. These results confirm the suitability of the proposed set of mRNAs to identify the potential transforming ability of NMs. Particular attention should be paid to the epigenome and especially to miRNAs for hazard assessment of NMs, as wells as for the study of the underlying mechanisms of action