Javier J. González

Genotoxic evaluation of five Angiotesin II receptor blockers: In vivo and in vitro micronucleus assay

Angiotensin II receptor blockers (ARBs) are a new class of drugs for the treatment of hypertension. In this study, we studied the potential genotoxic effects of five ARBs in vivo and in vitro in human peripheral blood lymphocytes (PBLs) by means of the cytokinesis-block micronucleous (CBMN) assay in combination with fluorescence in situ hybridization (FISH) with a centromeric probe. The nuclear division index (NDI) was used as a measure of cytotoxicity. We also analyzed the association between sex, age, duration of treatment and MN formation. The in vivo study was carried out in 55 hypertensive patients. The in vitro study was performed in 10 control individuals by adding the drugs to the culture medium at a final concentration similar to the levels found in plasma in patients. Our results showed a significant increase in the frequencies of MN and binucleated cells with MN (BNMN) in vivo and especially in vitro. We observed variability in the mean frequency of MN and BNMN among the five drugs analyzed. In vivo, patients treated with Candesartan, Telmisartan and Valsartan showed a statistical significant increase in these parameters, while Olmesartan showed the highest effect in vitro. We also found that the drugs inhibit the NDI in vitro and that Eprosartan, Olmesartan and Telmisartan are the ARBs studied with the highest effect in decreasing the proliferation of the cells. FISH analysis revealed no significant difference between patients and controls in the frequency of centromeric signals. A slight variability, without statistical significance, in the frequency of micronuclei with a centromere signal (CN(+)MN) was found among the different ARBs analyzed, ruling out an aneugenic potential. When accounting for risk factors, we found that in patients there is a positive correlation between MN, BNMN and sex and a negative correlation with duration of treatment.

Single nucleotide polymorphism and FMR1 CGG repeat instability in two Basque valleys.

Fragile X Syndrome (FXS, MIM 309550) is mainly due to the expansion of a CGG trinucleotide repeat sequence, found in the 5′ untranslated region of the FMR1 gene. Some studies suggest that stable markers, such as single nucleotide polymorphisms (SNPs) and the study of populations with genetic identity, could provide a distinct advance to investigate the origin of CGG repeat instability. In this study, seven SNPs (WEX28 rs17312728:G>T, WEX70 rs45631657:C>T, WEX1 rs10521868:A>C, ATL1 rs4949:A>G, FMRb rs25707:A>G, WEX17 rs12010481:C>T and WEX10 ss71651741:C>T) have been analyzed in two Basque valleys (Markina and Arratia). We examined the association between these SNPs and the CGG repeat size, the AGG interruption pattern and two microsatellite markers (FRAXAC1 and DXS548). The results suggest that in both valleys WEX28‐T, WEX70‐C, WEX1‐C, ATL1‐G, and WEX10‐C are preferably associated with cis‐acting sequences directly influencing instability. But comparison of the two valleys reveals also important differences with respect to: (1) frequency and structure of “susceptible” alleles and (2) association between “susceptible” alleles and STR and SNP haplotypes. These results may indicate that, in Arratia, SNP status does not identify a pool of susceptible alleles, as it does in Markina. In Arratia valley, the SNP haplotype association reveals also a potential new “protective” factor.

Evolution of mechanical behaviour in a structural steel subjected to high temperatures

Abstract In this work a study of how exposure to high temperatures can affect the mechanical properties of a structural steel is presented. To this end, several mechanical tests such as tensile, impact and microhardness tests have been carried out in order to compare the properties of the heat-exposed steel with those of an unaffected reference steel. Complementary compositional, metallographic and fractographic analyses have also been performed to try to cast some light on the problem. The results obtained allow us to extract some conclusions on the reutilization of the steel for structural applications.

Porous Asphalt Mixtures with 100% Siderurgic Aggregates

In this research, the possibility of making a porous asphalt mixture manufactured completely with recycled aggregates from carbon steel production was explored. Electric arc furnace slag (EAFS) was used as coarse aggregate and ladle furnace slag (LFS) as fine aggregate and filler. Initially, the properties of both slags and their suitability to be used in the manufacture of porous mixtures were analyzed. Then, a series of asphalt mixtures were developed incorporating these slags and they were compared with a reference mixture, made with conventional components. A series of tests were performed, including concepts such as mechanical behavior, durability, moisture susceptibility, rutting resistance, permeability or skid resistance. The results show that it is possible to make a suitable porous asphalt mixture with 100% of steel slag aggregates, complying with the standard requirements and obtaining a durable and environmentally sustainable mixture.

Performance of Hydraulic Mixes Manufactured with Electric Arc Furnace Slag Aggregates

Electric arc furnace slag (EAFS) has for many years simply been dumped in landfill sites; over the past few decades many researchers have investigated its reuse in cement mortar and concrete. By doing so, a waste product may be converted into a useful material with added value as a substitute for natural resources, the consumption of which is also minimized. Hydraulic mixes manufactured with EAFS normally have similar or even better hardened properties than mixes manufactured with natural aggregates. One disadvantage in the use of EAFS has been the poorer workability of the mixes, due to its higher density, porosity and water absorption levels. In this research, different EAFS mixes are manufactured and their properties in the fresh and the hardened state are closely analyzed; the results were very promising. The aim of this research is to demonstrate that EAFS concrete can achieve an acceptable workability at the correct dosages.

Cracking diagnostics of brake pedals during press forming operations

Abstract In this work a study of the cracking problems arising in manufacturing of steel brake pedals by press forming is presented. Cracks were detected in critical zones of the part revealing a possible lack of ductility in the constitutive material. In order to overcome this problem, a detailed study of the behaviour of the steel used has been carried out. In this way, mechanical characterization as well as microstructural analysis were performed over both cracked and uncracked pedals. The results obtained from this comparative analysis showed different microstructural features and, consequently, the dissimilar mechanical behaviour can be justified.