Toxicogenómica: Una aproximación integradora para explorar efectos tóxicos de nuevas moléculas y agilizar la selección de candidatos a desarrollo farmacéutico

Toxicogenómica: Una aproximación integradora para explorar efectos tóxicos de nuevas moléculas y agilizar la selección de candidatos a desarrollo farmacéutico

Investigadores relacionados con la evaluación de la seguridad de fármacos: formación y entrenamiento

Researchers in the area of drug safety assessment: Education and trainin

Neuronal in vitro models for the estimation of acute systemic toxicity

The objective of the EU funded integrated project ¿¿ACuteTox¿ is to develop a strategy in which general cytotoxicity, together with organ-specific endpoints and biokinetic features, are taken into consideration in the in vitro prediction of oral acute systemic toxicity. With regard to the nervous system, the effects of 23 reference chemicals were tested with approximately 50 endpoints, using a neuronal cell line, primary neuronal cell cultures, brain slices and aggregated brain cell cultures. Comparison of the in vitro neurotoxicity data with general cytotoxicity data generated in a non-neuronal cell line and with in vivo data such as acute human lethal blood concentration, revealed that GABAA receptor function, acetylcholine esterase activity, cell membrane potential, glucose uptake, total RNA expression and altered gene expression of NF-H, GFAP, MBP, HSP32 and caspase-3 were the best endpoints to use for further testing with 36 additional chemicals. The results of the second analysis showed that no single neuronal endpoint could give a perfect improvement in the in vitro¿in vivo correlation, indicating that several specific endpoints need to be analysed and combined with biokinetic data to obtain the best correlation with in vivo acute toxicity.JRC.DDG.I.3-In-vitro method

A Review of the Implementation of the Embryonic Stem Cell Test (EST)

The EST has been developed as an in vitro screening test for evaluating the potential embryotoxic effects of substances, to allow their classification into three major classes: non-embryotoxic; weakly embryotoxic; and strongly embryotoxic). It is biologically based on the assumption that chemicals with an embryotoxic potential will block the spontaneous development of embryonic stem cells into beating cardiac muscle cells within the first 10 days of embryonic development . In 2002, the assay was endorsed by the ECVAM Scientific Advisory Committee (ESAC) as scientifically validated and ready to be considered for regulatory acceptance and application. the workshop has reviewed the post validated status of the EST so far.JRC.DDG.I.3-In-vitro method

Metabolism: a Bottleneck in in Vitro Toxicological Test Development. The Report and Recommendations of ECVAM Workshop 54

Abstract is not availableJRC.I.2-Validation of biomedical testing method

Spatial variability of the relationships of runoff and sediment yield with weather types throughout the Mediterranean basin

Este artículo contiene 16 páginas, 6 figuras, 2 tablas.Soil degradation by water is a serious environmental problem worldwide, with specific climatic factors being the major causes. We investigated the relationships between synoptic atmospheric patterns (i.e. weather types, WTs) and runoff, erosion and sediment yield throughout the Mediterranean basin by analyzing a large database of natural rainfall events at 68 research sites in 9 countries. Principal Component Analysis (PCA) was used to identify spatial relationships of the different WTs including three hydro-sedimentary variables: rainfall, runoff, and sediment yield (SY, used to refer to both soil erosion measured at plot scale and sediment yield registered at catchment scale). The results indicated 4 spatial classes of rainfall and runoff: (a) northern sites dependent on North (N) and North West (NW) flows; (b) eastern sites dependent on E and NE flows; (c) southern sites dependent on S and SE flows; and, finally, (d) western sites dependent on W and SW flows. Conversely, three spatial classes are identified for SY characterized by: (a) N and NE flows in northern sites (b) E flows in eastern sites, and (c) Wand SW flows in western sites. Most of the rainfall, runoff and SY occurred during a small number of daily events, and just a few WTs accounted for large percentages of the total. Our results confirm that characterization by WT improves understanding of the general conditions under which runoff and SY occur, and provides useful information for understanding the spatial variability of runoff, and SY throughout the Mediterranean basin. The approach used here could be useful to aid of the design of regional water management and soil conservation measures.This research was supported by projects funded by the MINECOFEDER: CGL2014-52135-C3-3-R, CGL2014-59946-R, CGL2015-65569- R, CGL2015-64284-C2-2-R, and PCIN-2017-061/AEI. When this manuscript was first submitted Estela Nadal-Romero and Damià Vericat received a “Ramón y Cajal” postdoctoral contract (RYC-2013-14371 and RYC‐2010‐06264, Spanish Ministry of Economy and Competitiveness, MEC). Damià Vericat is now a Serra Húnter Fellow at the University of Lleida. María Fernández-Raga received a “José Castillejo” postdoctoral grant (Spanish Ministry of Education, Culture and Sports). Carla Ferreira was supported by a post-doctoral research grant from the Portuguese Science and Technology Foundation (SFRH/ BPD/120093/2016). Mariano Moreno-de las Heras received a Juan de la Cierva postdoctoral contract (IJCI-2015-26463) from the MEC. José Andrés López-Tarazón received a Vicenç Mut postdoctoral fellowship from the Autonomous Balearic Government (CAIB PD/038/2016). José Andrés López-Tarazón and Ramon Batalla also acknowledge the Secretariat for Universities and Research of the Department of the Economy and Knowledge of the Autonomous Government of Catalonia for supporting the Consolidated Research Group 2014 SGR 645 (RIUSFluvial Dynamics Research Group), and the CERCA Programme. This paper has benefited from the Lab and Field Data Pool created within the framework of the COST action CONNECTEUR (ES1306).Peer reviewe

Spatial variability of the relationships of runoff and sediment yield with weather types throughout the Mediterranean basin

Summarization: Soil degradation by water is a serious environmental problem worldwide, with specific climatic factors being the major causes. We investigated the relationships between synoptic atmospheric patterns (i.e. weather types, WTs) and runoff, erosion and sediment yield throughout the Mediterranean basin by analyzing a large database of natural rainfall events at 68 research sites in 9 countries. Principal Component Analysis (PCA) was used to identify spatial relationships of the different WTs including three hydro-sedimentary variables: rainfall, runoff, and sediment yield (SY, used to refer to both soil erosion measured at plot scale and sediment yield registered at catchment scale). The results indicated 4 spatial classes of rainfall and runoff: (a) northern sites dependent on North (N) and North West (NW) flows; (b) eastern sites dependent on E and NE flows; (c) southern sites dependent on S and SE flows; and, finally, (d) western sites dependent on W and SW flows. Conversely, three spatial classes are identified for SY characterized by: (a) N and NE flows in northern sites (b) E flows in eastern sites, and (c) W and SW flows in western sites. Most of the rainfall, runoff and SY occurred during a small number of daily events, and just a few WTs accounted for large percentages of the total. Our results confirm that characterization by WT improves understanding of the general conditions under which runoff and SY occur, and provides useful information for understanding the spatial variability of runoff, and SY throughout the Mediterranean basin. The approach used here could be useful to aid of the design of regional water management and soil conservation measures.Παρουσιάστηκε στο: Journal of Hydrolog