University of Extremadura

About: University of Extremadura is a education organization based out in Badajoz, Spain. It is known for research contribution in the topics: Population & Hyperspectral imaging. The organization has 7856 authors who have published 18299 publications receiving 396126 citations. The organization is also known as: Universidad de Extremadura.

When the hotter cools more quickly: mpemba effect in granular fluids

Abstract: • Ministerio de Economia, Industria y Competitividad. Beca FIS2013-42840-P (I+D+i), para Antonio Lasanta Becerra, Francisco Vega Reyes y Andres Santos Reyes • Ministerio de Economia, Industria y Competitividad. Beca FIS2016-76359-P (I+D+i), para Francisco Vega Reyes y Andres Santos Reyes • Ministerio de Economia, Industria y Competitividad. Beca MTM2014-56948-C2-2-P, para Antonio Lasanta Becerra • Junta de Extremadura y parcialmente Fondos Europeo de Desarrollo Regional. GR15104, para Antonio Lasanta Becerra, Francisco Vega Reyes y Andres Santos Reyes

The effect of the cytochrome P450 CYP2C8 polymorphism on the disposition of (R)‐ibuprofen enantiomer in healthy subjects

Abstract: Aims To study the effect of CYP2C8*3, the most common CYP2C8 variant allele on the dis-position of (R)-ibuprofen and the association of CYP2C8*3 with variant CYP2C9 alleles. Methods Three hundred and fifty-five randomly selected Spanish Caucasians were screened for the common CYP2C8 and CYP2C9 mutations. The pharmacokinetics of (R)-ibuprofen were studied in 25 individuals grouped into different CYP2C8 genotypes. Results The allele frequency of CYP2C8*3 (0.17) was found to be higher than that reported for other Caucasian populations (P = 0.0001). The frequencies of CYP2C9*2 and CYP2C9*3 were 0.19 (0.16–0.21) and 0.10 (0.08–0.12), respectively. An association between CYP2C8*3 and CYP2C9*2 alleles was observed, occurring together at a frequency 2.4-fold higher than expected for a random association of alleles (P = 0.0001). The presence of the CYP2C8*3 allele was found to influence the pharmacokinetics of (R)-ibuprofen in a gene–dose effect manner. Thus, after administration of 400 mg ibuprofen, the plasma half-life (95% confidence intervals) for individuals with genotypes CYP2C8*1/*1, CYP2C8*1/*3 and CYP2C8*3/*3, was 2.0 h (1.8–2.2), 4.2 h (1.9–6.5; P < 0.05) and 9.0 h (7.8–10.2; P < 0.002), respectively. A statistically significant trend with respect to the number of variant CYP2C8*3 alleles was also observed for the area under the concentration-time curve (P < 0.025), and drug clearance (P < 0.03). Conclusion Polymorphism of the CYP2C8 gene was found to be common, with nearly 30% of the population studied carrying the variant CYP2C8*3 allele. The presence of the latter caused a significant effect on the disposition of (R)-ibuprofen. This suggests that a substantial proportion of Caucasian subjects may show alterations in the disposition of drugs that are CYP2C8 substrates.

A mesenchymal-like phenotype and expression of CD44 predict lack of apoptotic response to sorafenib in liver tumor cells.

Abstract: The multikinase inhibitor sorafenib is the only effective drug in advanced cases of hepatocellular carcinoma (HCC). However, response differs among patients and effectiveness only implies a delay. We have recently described that sorafenib sensitizes HCC cells to apoptosis. In this work, we have explored the response to this drug of six different liver tumor cell lines to define a phenotypic signature that may predict lack of response in HCC patients. Results have indicated that liver tumor cells that show a mesenchymal-like phenotype, resistance to the suppressor effects of transforming growth factor beta (TGF-β) and high expression of the stem cell marker CD44 were refractory to sorafenib-induced cell death in in vitro studies, which correlated with lack of response to sorafenib in nude mice xenograft models of human HCC. In contrast, epithelial-like cells expressing the stem-related proteins EpCAM or CD133 were sensitive to sorafenib-induced apoptosis both in vitro and in vivo. A cross-talk between the TGF-β pathway and the acquisition of a mesenchymal-like phenotype with up-regulation of CD44 expression was found in the HCC cell lines. Targeted CD44 knock-down in the mesenchymal-like cells indicated that CD44 plays an active role in protecting HCC cells from sorafenib-induced apoptosis. However, CD44 effect requires a TGF-β-induced mesenchymal background, since the only overexpression of CD44 in epithelial-like HCC cells is not sufficient to impair sorafenib-induced cell death. In conclusion, a mesenchymal profile and expression of CD44, linked to activation of the TGF-β pathway, may predict lack of response to sorafenib in HCC patients.

Melatonin reduces lipid peroxidation and apoptotic-like changes in stallion spermatozoa.

Abstract: Lipid peroxidation (LPO) has been claimed as a major factor involved in stallion damage during storage or cryopreservation. Because melatonin is a well-known potent antioxidant, the aim of the present study was to investigate the effect of melatonin during in vitro incubation. Furthermore, we investigated the presence of specific melatonin receptors (MT1 and MT2) using specific polyclonal antibodies and western blotting. Stallion spermatozoa were incubated up to 3 hr at 37°C in the presence of different concentrations of melatonin (0, 50 pm, 100 pm, 200 pm, or 1 μm). At the beginning and at the end of the incubation period, sperm motility (using computer-assisted sperm analysis), membrane integrity and permeability, fluidity of the sperm membrane, LPO, and mitochondrial membrane potential (Δψm) were flow cytometrically evaluated. Melatonin reduced changes in the spermatozoa related to apoptosis (increased sperm membrane permeability and lowered Δψm) (P < 0.05). Furthermore, LPO was dramatically reduced (P < 0.01) while no effect was observed on sperm motility or kinematics. Interestingly, melatonin helped maintain a more fluid sperm plasmalemma (P < 0.05). Our results clearly show the absence of MT1 and MT2 receptors in the stallion spermatozoa. It is concluded that melatonin is a useful tool to improve the quality of stored stallion sperm, increasing their life span and reducing premature aging, this likely relates to melatonin's antioxidant properties.