Institute Investigacion Biomedica Of A Coruna Inibic

A Coruña, Spain

Institute Investigacion Biomedica Of A Coruna Inibic

A Coruña, Spain

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Linhart A.,Charles University | Monserrat L.,Institute Investigacion Biomedica Of A Coruna Inibic
International Journal of Cardiology | Year: 2010

Fabry disease, an X-linked lysosomal storage disorder affecting both men and women, is a relatively prevalent cause of hypertrophic cardiomyopathy (HCM) and is associated with significant morbidity and early death due to heart failure or ventricular arrhythmias. Fabry cardiomyopathy results from progressive build-up of glycosphingolipids in cardiac structures, but the underlying complex pathophysiologic mechanisms remain poorly understood. Disease-specific enzyme replacement therapy (ERT) is available for Fabry disease and, therefore, attention should be focused on early diagnosis of this progressive, life-threatening disease. Selected cardiology patients at high risk for Fabry disease can be tested using simple enzymatic assays, and diagnosis is confirmed by demonstration of a Fabry mutation. Testing cardiology patients with HCM of unknown etiology may identify previously unrecognized Fabry patients and allow genetic mapping to be carried out to identify other affected family members at a relatively early stage of the disease. Timely intervention early on in the disease is a key, as the best responses to ERT are seen in patients with the lowest degree of cardiac hypertrophy and fibrosis at the start of treatment. Crown Copyright © 2009.


Valdiglesias V.,University of La Coruña | Kilic G.,University of La Coruña | Costa C.,National Institute Of Health Dr Ricardo Jorge | Amor-Carro O.,Hospital Of La Santa Creu I Sant Pau | And 6 more authors.
Journal of Toxicology and Environmental Health - Part A: Current Issues | Year: 2012

One of the largest oil spill disasters in recent times was the accident of the oil tanker Prestige in front of the Galician coast in 2002. Thousands of people participated in the cleanup of the contaminated areas, being exposed to a complex mixture of toxic substances. Acute and prolonged respiratory symptoms and genotoxic effects were reported, although environmental exposure measurements were restricted to current determinations, such that attribution of effects observed to oil exposure is difficult to establish. The aim of this study was to analyze peripheral blood leukocytes (PBL) harvested from a rat model of subchronic exposure to a fuel oil with similar characteristics to that spilled by the Prestige tanker, in order to determine potential genotoxic effects under strictly controlled, in vivo exposure. Wistar Han and Brown Norway rats were exposed to the oil for 3 wk, and micronucleus test (MN) and comet assay, standard and modified with 8-oxoguanine DNA glycosylase (OGG1) enzyme, were employed to assess genotoxicity 72 h and 15 d after the last exposure. In addition, the potential effects of oil exposure on DNA repair capacity were determined by means of mutagen sensitivity assay. Results obtained from this study showed that inhalation oil exposure induced DNA damage in both Brown Norway and Wistar Han rats, especially in those animals evaluated 15 d after exposure. Although alterations in the DNA repair responses were noted, the sensitivity to oil substances varied depending on rat strain. Data support previous positive genotoxicity results reported in humans exposed to Prestige oil during cleanup tasks. © 2012 Copyright Taylor and Francis Group, LLC.


Gaytan F.,University of Cordoba, Spain | Gaytan F.,CIBER ISCIII | Gaytan F.,Instituto Maimonides Of Investigaciones Biomedicas Imibic | Sangiao-Alvarellos S.,University of La Coruña | And 24 more authors.
Endocrinology | Year: 2013

Lin28 (also termed Lin28a) and Lin28b are related RNA-binding proteins, involved in the control of microRNA synthesis, especially of the let-7 family, with putative functions in early (embryo) development. However, their roles during postnatal maturation remain ill defined. Despite the general assumption that Lin28 and Lin28b share similar targets and functions, conclusive demonstration of such redundancy is still missing. In addition, recent observations suggest a role of Lin28 proteins in mammalian reproduction, which is yet to be defined.Wedocument herein the patterns of RNA expression and protein distribution of Lin28 and Lin28b in mouse testis during postnatal development and in a model of hypogonadotropic hypogonadism as a result of inactivation of the kisspeptin receptor, Gpr54. Lin28 and Lin28b mRNAs were expressed in mouse testis across postnatal maturation, but their levels disparately varied between neonatal and pubertal periods, with peak Lin28 levels in infantile testes and sustained elevation of Lin28b mRNA in young adult male gonads, where relative levels of let-7a and let-7b miRNAs were significantly suppressed. In addition, Lin28 peptides displayed totally different patterns of cellular distribution in mouse testis: Lin28 was located in undifferentiated and type-A1 spermatogonia, whereas Lin28b was confined to spermatids and interstitial Leydig cells. These profiles were perturbed in Gpr54 null mouse testis, which showed preserved but irregular Lin28 signal and absence of Lin28b peptide, which was rescued by administration of gonadotropins, mainly hCG (as super-agonist of LH). In addition, increased relative levels of Lin28, but not Lin28b,mRNAand of let-7a/let-7b miRNAs were observed in Gpr54 KO mouse testes. Altogether, our data are the first to document the divergent patterns of cellular distribution and mRNA expression of Lin28 and Lin28b in the mouse testis along postnatal maturation and their alteration in a model of congenital hypogonadotropic hypogonadism. Our findings suggest distinct functional roles of these two related, but not overlapping, miRNAbinding proteins in the male gonad. Copyright © 2013 by The Endocrine Society.


Barallobre-Barreiro J.,Kings British Heart Foundation Center | Didangelos A.,Kings British Heart Foundation Center | Yin X.,Kings British Heart Foundation Center | Domenech N.,Institute Investigacion Biomedica Of A Coruna Inibic | Mayr M.,Kings British Heart Foundation Center
Methods in Molecular Biology | Year: 2013

Cardiacfibrosis is characterized by excessive deposition of extracellular matrix (ECM) and is a common complication of various cardiovascular diseases. However, little is known about proteins in the cardiac extracellular space. Proteomics analysis of cardiac ECM can be challenging due to the presence of more abundant intracellular proteins, the low degree of solubility of integral ECM proteins, and the presence of abundant posttranslational modifications. Here we describe an extraction methodology based on tissue decellularization, which allows the biochemical subfractionation of extracellular proteins in cardiac tissue. These relatively low-complexity protein fractions are suitable for analysis by gel-LC-MS/MS and other proteomics techniques. © Springer Science+Business Media New York 2013.


Bouzas-Mosquera A.,Complexo Hospitalario Universitario runa | Peteiro J.,Complexo Hospitalario Universitario runa | Broullon F.J.,Complexo Hospitalario Universitario runa | Calvino-Santos R.,Complexo Hospitalario Universitario runa | And 6 more authors.
European Journal of Internal Medicine | Year: 2015

Introduction Scarce data are available on the temporal patterns in clinical characteristics and outcomes of elderly patients referred for exercise stress testing. We aimed to assess the trends in baseline characteristics, tests results, referrals for invasive management, and mortality in these patients. Methods We evaluated 11,192 patients aged ≥ 65 years who were referred for exercise stress testing between January 1998 and December 2013. Calendar years were grouped into four quadrennia (1998-2001, 2002-2005, 2006-2009, and 2010-2013), and trends in clinical characteristics of the patients, type and results of the tests, referrals for invasive management, and mortality across the different periods were assessed. Results Despite a progressive decrease in the proportion of patients with non-interpretable baseline electrocardiograms or prior history of coronary artery disease, there was a gradual and marked increase in the use of cardiac imaging from 32.8% in 1998-2001 to 67.6% in 2010-2013 (p < 0.001). In addition, despite a gradual decline in the probability of positive exercise stress testing both without imaging (from 18.9 to 13.6%, p < 0.001) and with imaging assessment (from 40.2 to 29.7%, p < 0.001), the cumulative rate of coronary revascularization at 1 year increased (from 10.8 to 13.7%, p < 0.001). One-year mortality also decreased progressively from 3% to 1.6% (p < 0.001). Conclusions Among older adults referred for exercise stress testing, we observed a decline over time in the probability of inducible myocardial ischemia, an increase in the use of cardiac imaging and in the rate of coronary revascularization, and an improvement in the survival rate at 1 year. © 2015 European Federation of Internal Medicine.

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