Antihypertensive Mechanism of Lactoferrin-Derived Peptides: Angiotensin Receptor Blocking Effect

Texto del artículo, no incluye figuras ni tablas.Looking for antihypertensive mechanisms beyond ACE inhibition, we assessed whether lactoferrin (LF)-derived peptides can act as receptor blockers to inhibit vasoconstriction induced by angiotensin II or endothelin-1. The lactoferricin B (LfcinB)-derived peptide LfcinB20–25 (RRWQWR), the low molecular weight LF hydrolysate (LFH < 3 kDa), and two peptides identified in LFH < 3 kDa (LIWKL and RPYL) were tested in ex vivo assays of vasoactive responses. The peptide RPYL was tested in radioligand receptor binding assays. Both LFH < 3 kDa and individual peptides inhibited angiotensin II-induced vasoconstriction. RPYL showed the highest ex vivo inhibitory effect and also inhibited binding of [125I]-(Sar1,Ile8)-angiotensin II to AT1 receptors. By contrast, neither LFH < 3 kDa nor RPYL inhibited endothelin-1 and depolarization-induced vasoconstrictions. In conclusion, LF-derived peptides selectively inhibit angiotensin II-induced vasoconstriction by blocking angiotensin AT1 receptors. Therefore, inhibition of angiotensin II-induced vasocontriction is suggested as a mechanism contributing along with ACE inhibition to the antihypertensive effect of some LF-derived peptides.This work was supported by Grants AGL2010-21009 from Ministerio de Educación y Ciencia – FEDER, Consolider Ingenio 2010, Fun-C-Food, CSD2007-00063, and network RETICS INVICTUS – RD12/0014/0004 from Instituto de Salud Carlos III. R. Fernández-Musoles is the recipient of a fellowship from Ministerio de Educación y Ciencia (BES-2008-004472).Peer reviewe

Improving the performance of a preference-based multi-objective algorithm to optimize food treatment processes

This work focuses on the optimization of some high-pressure and temperature food treatments. In some cases, when dealing with real-life multi-objective optimization problems, such as the one considered here, the computational cost of evaluating the considered objective functions is usually quite high. Therefore, only a reduced number of iterations is affordable for the optimization algorithm. However, using fewer iterations can lead to inaccurate solutions far from the real Pareto optimal front. In this article, different mechanisms are analysed and compared to improve the convergence of a preference-based multi-objective optimization algorithm called the Weighting Achievement Scalarizing Function Genetic Algorithm (WASF-GA). The combination of these techniques has been applied to optimize a particular food treatment process. In particular, one of the proposed methods, based on the introduction of an advanced population, achieves important improvements in the quality indicator measures considered

Dynamic Identification of Damage in Brick Masonry Walls

This paper shows the experimental and numerical analysis developed on a brick masonry wall of 3x2.5x0.2 m to understand the changes on its dynamic behaviour with different stiffness situations: (i) original, (ii) loaded with different load levels, (iii) damaged by horizontal in plane loads, (iv) retrofitted with Textile Reinforced Mortars (TRM) and (v) retrofitted and damaged by horizontal in plane loads. This analysis has been developed at the Civil Engineering Lab at the University of Alicante. On this masonry wall a matrix of 8 seismic accelerometers have been installed to evaluate, in plane and out of plane, changes in the main frequencies, modal damping ratios and modal shapes. By the use of Operational Modal Analysis techniques the results shows that the changes on the stiffness have important influence on the main frequencies and in the modal damping ratios. Very low influence have been detected on the modal shapes due to the low level of external vibrations generated during the tests. Due to the low level of vibrations inside the lab,the classical application of ambient vibrations for OMA has been not possible and an external white noise force has been introduced on the top the wall by the use of a shaker to generate a general level of vibrations on the specimen

Implementation and validation of an economic module for the epidemiological model Be-FAST to predict the costs generated by livestock diseases epidemics. Application to the Classical Swine Fever case in Spain

Abstract Classical Swine Fever (CSF) is one of the most harmful livestock diseases for the economy of the swine sector worldwide. Specifically in Spain, the costs in the two last CSF outbreaks (1997 and 2001) have been estimated above 108 million euros. In this work, we aim to evaluate the economic impact of important livestock disease epidemics, and particularly the CSF in Spain. This study starts with a preliminary classification of the costs associated with CSF epidemics. In order to estimate the expected costs of a given epidemic in a considered area, a new economic module has been integrated into the epidemiological model Be-FAST, a time-spatial stochastic spread mathematical model for studying the transmission of diseases within and between farms. The input data for economic parameters have been obtained from entities related with the swine industry in Spain. The new Be-FAST module is tested by comparing the results obtained with historical data from CSF epidemics in Spain. The outcomes show that severe CSF epidemics also have a strong economic impact with around 80% of the costs related to animal culling, while costs associated with control measures are directly associated with the number of infected farms and the duration of the epidemic. The results presented in this work * Corresponding author: [email protected] 1 are expected to provide valuable information to decision makers, including animal health officials and insurance companies, and can be extended to other livestock diseases or used to predict the economic impact of future outbreaks

Fatigue Assessment of Old Riveted Railway Bridges: Laboratory Testing of a Real Bridge

The bridge over the Quisi Ravine in Alicante Province (Spain), built between 1913 and 1915, consists of six 22-22-42-42-22-22 m long steel Pratt truss spans, the lateral spans being isostatic and the central spans continuous. All the joints between the steel elements are riveted. As the bridge has been carrying railway traffic for more than 100 years, its condition needed to be assessed before carrying out the necessary repairs reinforcement to extend its service life. One of the most interesting tasks on the bridge involved a study of its fatigue behaviour to estimate its remaining useful life. Only a few kilometres away there happened to be another bridge with identical geometry over the Ferrandet Ravine, which had recently been dismantled and taken out of service and had carried the same railway traffic as the one over the Quisi Ravine. Advantage was therefore taken of this unique opportunity to test one of its isostatic spans in order to extrapolate the results to the Quisi Bridge. These tests were carried out at the ICITECH laboratories at the Universitat Politècnica de València in two different scenarios: 1) one test on a 22 m span, and 2) another on one of its girders, in both of which simulated railway traffic cyclical loads were applied. The results allowed us to estimate the number of trains that could pass over the bridge and its remaining service life, and also to define a monitoring method to help in decision making in case of possible failures of its component parts. The study also included an analysis of the bridge’s robustness in local failures of some of its elements, which led to a further bridge cyclical loading test with a deliberately damaged component. Even though other researchers had previously carried out fatigue tests on full-scale riveted bridge elements, the ICITECH study is unique in that it is the first time a full-scale bridge has been subjected to fatigue tests. This work was accompanied by advanced numerical modelling studies considering the fracture mechanics theory

PTGER4 gene variant rs76523431 is a candidate risk factor for radiological joint damage in rheumatoid arthritis patients: a genetic study of six cohorts

[Introduction] Prostaglandin E receptor 4 (PTGER4) is implicated in immune regulation and bone metabolism. The aim of this study was to analyze its role in radiological joint damage in rheumatoid arthritis (RA).[Methods] Six independent cohorts of patients with RA of European or North American descent were included, comprising 1789 patients with 5083 sets of X-rays. The Hospital Clínico San Carlos Rheumatoid Arthritis, Princesa Early Arthritis Register Longitudinal study, and Hospital Universitario de La Paz early arthritis (Spain) cohorts were used as discovery cohorts, and the Leiden Early Arthritis Clinic (The Netherlands), Wichita (United States), and National Databank for Rheumatic Diseases (United States and Canada) cohorts as replication cohorts. First, the PTGER4 rs6896969 single-nucleotide polymorphism (SNP) was genotyped using TaqMan assays and available Illumina Immunochip data and studied in the discovery and replication cohorts. Second, the PTGER4 gene and adjacent regions were analyzed using Immunochip genotyping data in the discovery cohorts. On the basis of pooled p values, linkage disequilibrium structure of the region, and location in regions with transcriptional properties, SNPs were selected for replication. The results from discovery, replication, and overall cohorts were pooled using inverse-variance–weighted meta-analysis. Influence of the polymorphisms on the overall radiological damage (constant effect) and on damage progression over time (time-varying effect) was analyzed.[Results] The rs6896969 polymorphism showed a significant association with radiological damage in the constant effect pooled analysis of the discovery cohorts, although no significant association was observed in the replication cohorts or the overall pooled analysis. Regarding the analysis of the PTGER4 region, 976 variants were analyzed in the discovery cohorts. From the constant and time-varying effect analyses, 12 and 20 SNPs, respectively, were selected for replication. Only the rs76523431 variant showed a significant association with radiographic progression in the time-varying effect pooled analysis of the discovery, replication, and overall cohorts. The overall pooled effect size was 1.10 (95 % confidence interval 1.05–1.14, p = 2.10 × 10−5), meaning that radiographic yearly progression was 10 % greater for each copy of the minor allele.[Conclusions] The PTGER4 gene is a candidate risk factor for radiological progression in RA.This work was supported by the Instituto de Salud Carlos III (ISCIII), Ministry of Health, Spain [Miguel Servet research contract CP12/03129 (to LRR); Fondo de Investigaciones Sanitarias PI11/02413; and Red de Investigación en Inflamación y Enfermedades Reumáticas RD12/0009/0004, RD12/0009/0011, and RD12/0009/0017]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe

Non Thermal Irreversible Electroporation: Novel Technology for Vascular Smooth Muscle Cells Ablation

Non thermal Irreversible electroporation (NTIRE) is a new tissue ablation method that induces selective damage only to the cell membrane while sparing all other tissue components. Our group has recently showed that NTIRE attenuated neointimal formation in rodent model. The goal of this study was to determine optimal values of NTIRE for vascular smooth muscle cell (VSMC) ablation.33 Sprague-Dawley rats were used to compare NTIRE protocols. Each animal had NTIRE applied to its left common carotid artery using a custom-made electrodes. The right carotid artery was used as control. Electric pulses of 100 microseconds were used. Eight IRE protocols were compared: 1-4) 10 pulses at a frequency of 10 Hz with electric fields of 3500, 1750, 875 and 437.5 V/cm and 5-8) 45 and 90 pulses at a frequency of 1 Hz with electric fields of 1750 and 875 V/cm. Animals were euthanized after one week. Histological analysis included VSMC counting and morphometry of 152 sections. Selective slides were stained with elastic Van Gieson and Masson trichrome to evaluate extra-cellular structures. The most efficient protocols were 10 pulses of 3500 V/cm at a frequency of 10 Hz and 90 pulses of 1750 V/cm at a frequency of 1 Hz, with ablation efficiency of 89+/-16% and 94+/-9% respectively. Extra-cellular structures were not damaged and the endothelial layer recovered completely.NTIRE is a promising, efficient and simple novel technology for VMSC ablation. It enables ablation within seconds without causing damage to extra-cellular structures, thus preserving the arterial scaffold and enabling endothelial regeneration. This study provides scientific information for future anti-restenosis experiments utilizing NTIRE