Health Research Institute Hospital la Fe

Valencia, Spain

Health Research Institute Hospital la Fe

Valencia, Spain

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PubMed | Health Research Institute Hospital La Fe, Leitat Technological Center and University of Oslo
Type: | Journal: Scientific reports | Year: 2017

The prompt and reliable identification of infants at risk of hypoxic-ischemic encephalopathy secondary to perinatal asphyxia in the first critical hours is important for clinical decision-making and yet still remains a challenge. This work strives for the evaluation of a panel of metabolic biomarkers that have been associated with the hypoxic-ischemic insult in the perinatal period. Plasma and urine samples from a consolidated newborn piglet model of hypoxia and withdrawn before and at different time points after a hypoxic insult were analyzed and compared to a control group. Time-dependent metabolic biomarker profiles were studied and observed patterns were similar to those of lactate levels, which are currently considered the gold standard for assessing hypoxia. Class prediction performance could be improved by the use of a combination of the whole panel of determined metabolites in plasma as compared to lactate values. Using a multivariate model including lactate together with the studied metabolic biomarkers allowed to improve the prediction performance of duration of hypoxia time, which correlates with the degree of brain damage. The present study evidences the usefulness of choline and related metabolites for improving the early assessment of the severity of the hypoxic insult.


PubMed | Health Research Institute Hospital La Fe, Leitat Technological Center and University of Oslo
Type: Journal Article | Journal: Pediatric research | Year: 2016

Perinatal hypoxic-ischemic brain damage is a major cause of mortality and morbidity in the neonatal period. Currently, limited ranges of biochemical tests assessing the intensity and duration of hypoxia are ready for clinical use. However, the need to initiate hypothermia therapy early after the clinical suspicion of hypoxic-ischemic encephalopathy requires the availability of early and reliable hypoxia markers. We have sought these biomarkers in an experimental model of hypoxia reoxygenation.Hypoxia and hypotension were induced in newborn piglets following a standardized model and reoxygenation was carried out using room air (RA). An untargeted liquid chromatography-time of flight mass spectrometry (LC-TOFMS) approach was used to assess changes in the metabolomic profile of plasma samples after intense hypoxia and upon reoxygenation.At the end of hypoxia, the plasma metabolome showed an increased plasma concentration of analytes reflecting a metabolic adaptation to prolonged anaerobiosis. However, after resuscitation, metabolite levels returned to the starting values.Severe hypoxia induces early, significant, and transient changes of specific metabolites in the plasma metabolome, which represent a snapshot of the biochemical adaptation of mammals to intense hypoxia. These metabolites could have applicability in predicting the severity of hypoxia in the clinical setting.


Vento M.,Polytechnic University of Valencia | Vento M.,Health Research Institute Hospital La Fe | Escobar J.,Health Research Institute Hospital La Fe | Cernada M.,Health Research Institute Hospital La Fe | And 2 more authors.
Clinics in Perinatology | Year: 2012

This article describes aerobic metabolism, oxygen free radicals, antioxidant defenses, oxidative stress, inflammatory response and redox signaling, the fetal to neonatal transition, arterial oxygen saturation, oxygen administration in the delivery room, oxygen during neonatal care in the NICU, evolving oxygen needs in the first few weeks of life, and complications that can occur when infants go home from the hospital on oxygen. © 2012 Elsevier Inc.


Beskers T.F.,Karlsruhe Institute of Technology | Beskers T.F.,PSS Polymer Standards Service GmbH | Brandstetter M.,Vienna University of Technology | Kuligowski J.,Health Research Institute Hospital la Fe | And 3 more authors.
Analyst | Year: 2014

This work introduces a tunable mid-infrared (mid-IR) external cavity quantum cascade laser (EC-QCL) as a new molecular specific detector in liquid chromatography. An EC-QCL with a maximum tunability of 200 cm-1 (1030-1230 cm-1) was coupled to isocratic high performance liquid chromatography (HPLC) for the separation of sugars with a cation exchange column (counter ion: Ca2+) and distilled water as the mobile phase. Transmission measurements in a 165 μm thick flow cell allowed for on-line coupling and independent quantification of glucose, fructose and sucrose in the concentration range from 5 mg mL-1 to 100 mg mL-1 in several beverages. The results obtained with the EC-QCL detector were found to be in good agreement with those obtained using a differential refractive index detector as a reference. The standard deviation of the method for the linear calibration was better than 5 mg mL-1 for all sugars and reached a minimum of 1.9 mg mL-1, while the DRI detector reached a minimum of 1 mg mL-1. Besides the quantification of sugars for which a calibration was performed, also chromatographic peaks of other components could be identified on the basis of their IR absorption spectra. This includes taurine, ethanol, and sorbitol. This journal is © the Partner Organisations 2014.


Jimenez-Serrano S.,Polytechnic University of Valencia | Tortajada S.,Polytechnic University of Valencia | Tortajada S.,Health Research Institute Hospital la Fe | Garcia-Gomez J.M.,Polytechnic University of Valencia | Garcia-Gomez J.M.,Health Research Institute Hospital la Fe
Telemedicine and e-Health | Year: 2015

Background: Postpartum depression (PPD) is a disorder that often goes undiagnosed. The development of a screening program requires considerable and careful effort, where evidence-based decisions have to be taken in order to obtain an effective test with a high level of sensitivity and an acceptable specificity that is quick to perform, easy to interpret, culturally sensitive, and cost-effective. The purpose of this article is twofold: first, to develop classification models for detecting the risk of PPD during the first week after childbirth, thus enabling early intervention; and second, to develop a mobile health (m-health) application (app) for the Android® (Google, Mountain View, CA) platform based on the model with best performance for both mothers who have just given birth and clinicians who want to monitor their patient's test. Materials and Methods: A set of predictive models for estimating the risk of PPD was trained using machine learning techniques and data about postpartum women collected from seven Spanish hospitals. An internal evaluation was carried out using a hold-out strategy. An easy flowchart and architecture for designing the graphical user interface of the m-health app was followed. Results: Naive Bayes showed the best balance between sensitivity and specificity as a predictive model for PPD during the first week after delivery. It was integrated into the clinical decision support system for Android mobile apps. Conclusions: This approach can enable the early prediction and detection of PPD because it fulfills the conditions of an effective screening test with a high level of sensitivity and specificity that is quick to perform, easy to interpret, culturally sensitive, and cost-effective. © 2015, Mary Ann Liebert, Inc.


Molina-Navarro M.M.,Health Research Institute Hospital la Fe | Rosello-Lleti E.,Health Research Institute Hospital la Fe | Tarazon E.,Health Research Institute Hospital la Fe | Ortega A.,Health Research Institute Hospital la Fe | And 8 more authors.
International Journal of Cardiology | Year: 2013

Background Heart failure (HF) induces alterations in nucleocytoplasmic transport, which is essential to the cardiomyocyte biology. The objective of this study was to analyze the changes in gene expression in human HF, particularly focusing on nucleocytoplasmic transport-related genes. Methods and results 29 RNA heart samples from dilated cardiomyopathy (DCM, n = 12) and ischemic cardiomyopathy (ICM, n = 12) patients undergoing heart transplantation and control donors (CNT, n = 5) were extracted to perform a microarray profiling using Affymetrix Human Gene® 1.0 ST arrays. We focused on the study of 5 nucleocytoplasmic transport-related genes, since this functional category has not previously been studied in HF. XPO1, GABPB2, and RANBP17 were upregulated, while KALRN was downregulated in both DCM and ICM, and XPO5 only in DCM. Validation of the results by RT-qPCR increasing the total heart samples up to 41 showed a high degree of consistency with microarray results. Moreover, we observed a strong relationship between the XPO1 mRNA and robust left ventricular function parameters in ICM: left ventricular end-systolic (r = 0.81, p < 0.0001) and end-diastolic diameters (r = 0.80, p < 0.0001), and ejection fraction (r = - 0.57, p < 0.05). Conclusions We show that the expression of nucleocytoplasmic transport-related genes is altered in HF. Furthermore, XPO1 mRNA level is closely related with robust left ventricular function parameters in ICM patients. These changes may help to distinguish DCM and ICM in HF at the level of the transcriptome and provide a base for novel therapeutic approaches. © 2013 Elsevier Ireland Ltd. All rights reserved.


PubMed | Health Research Institute Hospital La Fe, Vienna University of Technology, Assiut University and Polytechnic University of Valencia
Type: Journal Article | Journal: The Analyst | Year: 2016

Biothiols play an essential role in a number of biological processes in living organisms including detoxification and metabolism. Fetal to neonatal transition poses a pro-oxidant threat for newborn infants, especially those born prematurely. A reliable and rapid tool for the direct determination of thiols in small volume whole blood (WB) samples would be desirable for its application in clinical practice. This study shows the feasibility of Surface Enhanced Raman Spectroscopy (SERS) using a silver colloid prepared by reduction of silver nitrate using hydroxylamine, as the SERS substrate for the quantification of thiols in WB samples after a simple precipitation step for protein removal. Bands originating from biothiols (790, 714 and 642 cm(-1)) were enhanced by the employed SERS substrate and the specificity of the detected SERS signal was tested for molecules presenting -SH functional groups. A statistically significant correlation between the obtained SERS signals and the thiol concentration measured using a chromatographic reference method in umbilical cord WB samples could be demonstrated. Using WB GSH concentrations obtained from the chromatographic reference procedure, a Partial Least Squares (PLS) regression model covering GSH concentrations from 13 to 2200 M was calculated obtaining a root mean square error of prediction (RMSEP) of 381 M when applied to an external test set. The developed approach uses small blood sample volumes (50 L), which is important for clinical applications, especially in the field of neonatology. This feasibility study shows that the present approach combines all the necessary characteristics for its potential application in clinical practice.


PubMed | Health Research Institute Hospital La Fe, University of Santiago de Compostela, University of Valencia and Sistemas Genomicos
Type: Journal Article | Journal: PloS one | Year: 2014

Heart failure provokes alterations in the expression of nucleocytoplasmic transport-related genes. To elucidate the nucleocytoplasmic transport-linked functional network underlying the two major causes of heart failure, ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM), we examined global transcriptome profiles of left ventricular myocardium tissue samples from 31 patients (ICM, n=10; DCM, n=13) undergoing heart transplantation and control donors (CNT, n=8) using RNA-Sequencing and GeneMANIA. Comparative profiling of ICM versus control and DCM versus control showed 1081 and 2440 differentially expressed genes, respectively (>1.29-fold; P<0.05). GeneMANIA revealed differentially regulated functional networks specific to ICM and DCM. In comparison with CNT, differential expression was seen in 9 and 12 nucleocytoplasmic transport-related genes in ICM and DCM groups, respectively. DDX3X, KPNA2, and PTK2B were related to ICM, while SMURF2, NUP153, IPO5, RANBP3, NOXA1, and RHOJ were involved in DCM pathogenesis. Furthermore, the two pathologies shared 6 altered genes: XPO1, ARL4, NFKB2, FHL3, RANBP2, and RHOU showing an identical trend in expression in both ICM and DCM. Notably, the core of the derived functional networks composed of nucleocytoplasmic transport-related genes (XPO1, RANBP2, NUP153, IPO5, KPNA2, and RANBP3) branched into several pathways with downregulated genes. Moreover, we identified genes whose expression levels correlated with left ventricular mass index and left ventricular function parameters in HF patients. Collectively, our study provides a clear distinction between the two pathologies at the transcriptome level and opens up new possibilities to search for appropriate therapeutic targets for ICM and DCM.


PubMed | Hospital La Fe, Health Research Institute Hospital La Fe, University of Santiago de Compostela and Hospital Nacional Of Paraplejicos
Type: Journal Article | Journal: PloS one | Year: 2014

Dilated cardiomyopathy (DCM) is a public health problem with no available curative treatment, and mitochondrial dysfunction plays a critical role in its development. The present study is the first to analyze the mitochondrial proteome in cardiac tissue of patients with DCM to identify potential molecular targets for its therapeutic intervention.16 left ventricular (LV) samples obtained from explanted human hearts with DCM (n=8) and control donors (n=8) were extracted to perform a proteomic approach to investigate the variations in mitochondrial protein expression. The proteome of the samples was analyzed by quantitative differential electrophoresis and Mass Spectrometry. These changes were validated by classical techniques and by novel and precise selected reaction monitoring analysis and RNA sequencing approach increasing the total heart samples up to 25. We found significant alterations in energy metabolism, especially in molecules involved in substrate utilization (ODPA, ETFD, DLDH), energy production (ATPA), other metabolic pathways (AL4A1) and protein synthesis (EFTU), obtaining considerable and specific relationships between the alterations detected in these processes. Importantly, we observed that the antioxidant PRDX3 overexpression is associated with impaired ventricular function. PRDX3 is significantly related to LV end systolic and diastolic diameter (r=0.73, p value<0.01; r=0.71, p value<0.01), fractional shortening, and ejection fraction (r=-0.61, p value<0.05; and r=-0.62, p value<0.05, respectively).This work could be a pivotal study to gain more knowledge on the cellular mechanisms related to the pathophysiology of this disease and may lead to the development of etiology-specific heart failure therapies. We suggest new molecular targets for therapeutic interventions, something that up to now has been lacking.


PubMed | Health Research Institute Hospital La Fe
Type: Journal Article | Journal: Journal of cellular and molecular medicine | Year: 2015

Mitochondrial dysfunction plays a critical role in the development of ischaemic cardiomyopathy (ICM). In this study, the mitochondrial proteome in the cardiac tissue of ICM patients was analysed by quantitative differential electrophoresis (2D-DIGE) and mass spectrometry (MS) for the first time to provide new insights into cardiac dysfunction in this cardiomyopathy. We isolated mitochondria from LV samples of explanted hearts of ICM patients (n=8) and control donors (n=8) and used a proteomic approach to investigate the variations in mitochondrial protein expression. We found that most of the altered proteins were involved in cardiac energy metabolism (82%). We focused on ATPA, which is involved in energy production, and dihydrolipoyl dehydrogenase, implicated in substrate utilization, and observed that these molecules were overexpressed and that the changes detected in the processes mediated by these proteins were closely related. Notably, we found that ATPA overexpression was associated with reduction in LV mass (r=-0.74, P<0.01). We also found a substantial increase in the expression of elongation factor Tu, a molecule implicated in protein synthesis, and PRDX3, involved in the stress response. All of these changes were validated using classical techniques and by using novel and precise selected reaction monitoring analysis and an RNA sequencing approach, with the total heart samples being increased to 24. This study provides key insights that enhance our understanding of the cellular mechanisms related to the pathophysiology of ICM and could lead to the development of aetiology-specific heart failure therapies. ATPA could serve as a molecular target suitable for new therapeutic interventions.

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