The value of selected in vitro and in silico methods to predict acute oral toxicity in a regulatory context: results from the European Project ACuteTox

ACuteTox is a project within the 6th European Framework Programme which had as one of its goals to develop, optimise and prevalidate a non-animal testing strategy for predicting human acute oral toxicity. In its last 6months, a challenging exercise was conducted to assess the predictive capacity of the developed testing strategies and final identification of the most promising ones. Thirty-two chemicals were tested blind in the battery of in vitro and in silico methods selected during the first phase of the project. This paper describes the classification approaches studied: single step procedures and two step tiered testing strategies. In summary, four in vitro testing strategies were proposed as best performing in terms of predictive capacity with respect to the European acute oral toxicity classification. In addition, a heuristic testing strategy is suggested that combines the prediction results gained from the neutral red uptake assay performed in 3T3 cells, with information on neurotoxicity alerts identified by the primary rat brain aggregates test method. Octanol-water partition coefficients and in silico prediction of intestinal absorption and blood-brain barrier passage are also considered. This approach allows to reduce the number of chemicals wrongly predicted as not classified (LD(50)>2000mg/kg b.w.).Peer Reviewe

S100B as a potential biomarker and therapeutic target in multiple sclerosis

Multiple sclerosis (MS) pathology is characterized by neuroinflammation and demyelination. Recently, the inflammatory molecule S100B was identified in cerebrospinal fluid (CSF) and serum of MS patients. Although seen as an astrogliosis marker, lower/physiological levels of S100B are involved in oligodendrocyte differentiation/maturation. Nevertheless, increased S100B levels released upon injury may induce glial reactivity and oligodendrocyte demise, exacerbating tissue damage during an MS episode or delaying the following remyelination. Here, we aimed to unravel the functional role of S100B in the pathogenesis of MS. Elevated S100B levels were detected in the CSF of relapsing-remitting MS patients at diagnosis. Active demyelinating MS lesions showed increased expression of S100B and its receptor, the receptor for advanced glycation end products (RAGE), in the lesion area, while chronic active lesions displayed increased S100B in demyelinated areas with lower expression of RAGE in the rim. Interestingly, reactive astrocytes were identified as the predominant cellular source of S100B, whereas RAGE was expressed by activated microglia/macrophages. Using an ex vivo demyelinating model, cerebral organotypic slice cultures treated with lysophosphatidylcholine (LPC), we observed a marked elevation of S100B upon demyelination, which co-localized mostly with astrocytes. Inhibition of S100B action using a directed antibody reduced LPC-induced demyelination, prevented astrocyte reactivity and abrogated the expression of inflammatory and inflammasome-related molecules. Overall, high S100B expression in MS patient samples suggests its usefulness as a diagnostic biomarker for MS, while the beneficial outcome of its inhibition in our demyelinating model indicates S100B as an emerging therapeutic target in MS.This work was supported by Medal of Honor L’Oréal for Women in Science (FCT, UNESCO, L’Óreal) and innovation grant (Ordem dos Farmacêuticos) to AF, a post-doctoral grant from Fundação para a Ciência e Tecnologia (FCT-SFRH/BPD/96794/2013) and a DuPré Grant from the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) to AB, and by FCT-Pest- OE/SAU/UI4013 to iMed.ULisboa.info:eu-repo/semantics/publishedVersio

Comparação de três métodos de estimativa da evapotranspiração de referência para a região de Araraquara - SP

Uma forma de verificar a eficiência de métodos de estimativa da evapotranspiração de referência (ETo) é a comparação com o método-padrão. Este trabalho tem por finalidade comparar três métodos de estimativa da ETo: Radiação Solar (RS), Makkink (MAK) e Tanque Classe A (TCA) em relação ao método de Penman-Monteith (PM), em dois períodos distintos das fases de desenvolvimento da cultura de citros, com dados médios quinzenais para os períodos inverno-primavera e verão-outono. A pesquisa foi desenvolvida em uma fazenda de citros, em Araraquara - SP, onde foi instalada uma estação meteorológica automatizada e um tanque Classe A. Por intermédio da estação meteorológica automatizada, foram obtidas medidas da radiação solar global, saldo de radiação, temperatura do ar, umidade relativa do ar e velocidade do vento. A análise de regressão indica que, para o método TCA, pode ser utilizado o modelo de regressão y = bx, em que, y representa a EToPM e x a EToTCA. Para os demais métodos analisados, o modelo mais adequado foi y = bx + a. Os resultados obtidos neste estudo evidenciam que o método do TCA superestimou a ETo em 26% no período verão-outono e em 24% no período inverno-primavera. O método de MAK subestimou a ETo nos dois períodos analisados, enquanto o método da RS superestimou a ETo.To verify the efficiency of the evapotranspiration reference methods (ETo), it is necessary to contrast with the standard method. This work has the purpose to compare three methods of ETo estimation: Solar Radiation (RS), Makkink (MAK) and a Class A tank (TCA) method with Penman-Monteith method (PM), in two phases of citrus growth, working with biweekly medium data for the winter-spring and summer-autumn periods. The research was developed in a citrus farm, in Araraquara - SP, Brazil, where it was installed an automated meteorological station and a Class A tank. Through a system of data acquisition, measures of the global solar radiation, radiation balance, temperature of the air, relative humidity of the air and speed of the wind, were obtained. The linear regression analysis shows that the TCA method can be fitted by, y = bx, where y represents EToPM and x represents EToTCA. For the others analyzed methods we found the model y = bx + a. The results of this study indicate that the TCA method overestimated ETo 26% in the summer-autumn period and 24% in the winter-spring period. The MAK method, underestimated ETo in the two analyzed periods, while the RS method overestimated ETo

Water stress indices for the sugarcane crop on different irrigated surfaces

ABSTRACT Sugarcane (Saccharum officinarum L.) is a crop of vital importance to Brazil, in the production of sugar and ethanol, power generation and raw materials for various purposes. Strategic information such as topography and canopy temperature can provide management technologies accessible to farmers. The objective of this study was to determine water stress indices for sugarcane in irrigated areas, with different exposures and slopes. The daily water stress index of the plants and the water potential in the soil were evaluated and the production system was analyzed. The experiment was carried out in an “Experimental Watershed”, using six surfaces, two horizontal and the other ones with 20 and 40% North and South exposure slopes. Water stress level was determined by measuring the temperatures of the vegetation cover and the ambient air. Watering was carried out using a drip irrigation system. The results showed that water stress index of sugarcane varies according to exposure and slope of the terrain, while areas whose water stress index was above 5.0 oC had lower yield values

Estimation methods of reference evapotranspiration (ETo) for Uberlândia -MG

One approach to verify the adequacy of estimation methods of reference evapotranspiration is the comparison with the Penman-Monteith method, recommended by the United Nations of Food and Agriculture Organization - FAO, as the standard method for estimating ET0. This study aimed to compare methods for estimating ET0, Makkink (MK), Hargreaves (HG) and Solar Radiation (RS), with Penman-Monteith (PM). For this purpose, we used daily data of global solar radiation, air temperature, relative humidity and wind speed for the year 2010, obtained through the automatic meteorological station, with latitude 18° 91' 66 S, longitude 48° 25' 05 W and altitude of 869m, at the National Institute of Meteorology situated in the Campus of Federal University of Uberlandia - MG, Brazil. Analysis of results for the period were carried out in daily basis, using regression analysis and considering the linear model y = ax, where the dependent variable was the method of Penman-Monteith and the independent, the estimation of ET0 by evaluated methods. Methodology was used to check the influence of standard deviation of daily ET0 in comparison of methods. The evaluation indicated that methods of Solar Radiation and Penman-Monteith cannot be compared, yet the method of Hargreaves indicates the most efficient adjustment to estimate ETo.Uma forma de verificar a adequação de métodos de estimativa da evapotranspiração de referência (ETo) é a comparação com o método de Penman-Monteith, recomendado pela Organização das Nações Unidas para Alimentação e Agricultura – FAO, como método-padrão para estimativa da ETo. Este estudo teve por objetivo comparar os métodos de estimativa da ETo, Makkink (MK), Hargreaves (HG) e Radiação Solar (RS), com o método de Penman-Monteith (PM). Para tanto, utilizaram-se dados diários de radiação solar global, velocidade do vento, temperatura e umidade relativa do ar para o ano de 2010, obtidos na estação meteorológica automática, com latitude de 18º91’66”S, longitude de 48º25’05”W e altitude de 869 m, do Instituto Nacional de Meteorologia, instalado no Câmpus da Universidade Federal de Uberlândia - MG. As análises dos resultados foram feitas para o período diário, utilizando-se da análise de regressão linear y = a x, na qual a variável dependente foi o método de Penman-Monteith, e a independente, as estimativas da ETo pelos métodos avaliados. Utilizou-se da metodologia que verifica a influência do desvio-padrão diário da ETo na comparação dos métodos estudados. Os métodos de Radiação Solar e Penman-Monteith não podem ser comparados, já o método de Hargreaves indica ajuste mais eficiente para a estimativa da ETo