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Acuna-Castroviejo D.,University of Granada | Acuna-Castroviejo D.,Hospital Universitario San Cecilio | Escames G.,University of Granada | Venegas C.,University of Granada | And 6 more authors.
Cellular and Molecular Life Sciences | Year: 2014

Endogenous melatonin is synthesized from tryptophan via 5-hydroxytryptamine. It is considered an indoleamine from a biochemical point of view because the melatonin molecule contains a substituted indolic ring with an amino group. The circadian production of melatonin by the pineal gland explains its chronobiotic influence on organismal activity, including the endocrine and non-endocrine rhythms. Other functions of melatonin, including its antioxidant and anti-inflammatory properties, its genomic effects, and its capacity to modulate mitochondrial homeostasis, are linked to the redox status of cells and tissues. with the aid of specific melatonin antibodies, the presence of melatonin has been detected in multiple extrapineal tissues including the brain, retina, lens, cochlea, Harderian gland, airway epithelium, skin, gastrointestinal tract, liver, kidney, thyroid, pancreas, thymus, spleen, immune system cells, carotid body, reproductive tract, and endothelial cells. In most of these tissues, the melatonin-synthesizing enzymes have been identified. Melatonin is present in essentially all biological fluids including cerebrospinal flluid, saliva, bile, synovial fluid, amniotic fluid, and breast milk. In several of these fluids, melatonin concentrations exceed those in the blood. The importance of the continual availability of melatonin at the cellular level is important for its physiological regulation of cell homeostasis, and may be relevant to its therapeutic applications. Because of this, it is essential to compile information related to its peripheral production and regulation of this ubiquitously acting indoleamine. Thus, this review emphasizes the presence of melatonin in extrapineal organs, tissues, and fluids of mammals including humans. © Springer Basel 2014.


Ozturk G.,Maltepe University | Akbulut K.G.,Gazi University | Guney S.,Gazi University | Acuna-Castroviejo D.,University of Granada | Acuna-Castroviejo D.,Hospital Universitario San Cecilio
Experimental Gerontology | Year: 2012

Oxidative stress is an important factor for aging. The antioxidative enzymes glutathione peroxidase (GPx), glutathione reductase (GRd) and superoxide dismutase (SOD) play a crucial role protecting the organism against the age-dependent oxidative stress. Glutathione (GSH) is present in nearly all living cells. GSH is one of the main antioxidants in the cell and it serves several physiological functions. Our purpose was to evaluate the age-related changes in mitochondrial GPx, GRd and SOD activities, and mitochondrial GSH pool in the brains of young (3. months) and aged rats (24. months). We also investigated whether melatonin administration influences these brain mitochondrial enzyme activities and GSH levels in young and aged rats. The results showed that GPx activity increased with age, whereas melatonin treatment decreased GPx activity in the aged rats at levels similar to those in young and young. +. melatonin groups. The activities of GRd and SOD, however, did not change with age. But, melatonin treatment increased SOD activity in the aged rats. GSH levels, which also increased with age, were not modified by melatonin treatment. The reduction in the SOD/GPx and GR/GPx ratios with age was prevented by melatonin administration. Together, our results suggest that the age-related oxidative stress in rat brain mitochondria is more apparent when the antioxidant enzyme ratios are analyzed instead of their absolute values. The antioxidative effects of melatonin were also supported by the recovery of the enzyme ratios during aging. © 2012 Elsevier Inc.


Leno-Duran E.,University of Granada | Munoz-Fernandez R.,Institute Parasitologia y Biomedicina Lopez Neyra | Garcia Olivares E.,University of Granada | Garcia Olivares E.,Hospital Universitario San Cecilio | And 2 more authors.
Cellular and Molecular Immunology | Year: 2014

A successful pregnancy relies on immunological adaptations that allow the fetus to grow and develop in the uterus, despite being recognized by maternal immune cells. Among several immunocompetent cell types present within the human maternal/fetal interface, DC-SIGN + dendritic cells (DCs) and CD56 + natural killer (NK) cells are of major importance for early pregnancy maintenance, not only generating maternal immunological tolerance but also regulating stromal cell differentiation. Previous reports show the presence of NK-DC cell conjugates in first trimester human decidua, suggesting that these cells may play a role in the modulation of the local immune response within the uterus. While effective immunity is necessary to protect the mother from harmful pathogens, some form of tolerance must be activated to avoid an immune response against fetal antigens. This review article discusses current evidence concerning the functions of DC and NK cells in pregnancy and their liaison in human decidua. © 2014 CSI and USTC. All rights reserved.


Garcia-Martin A.,Hospital Universitario San Cecilio | Rozas-Moreno P.,Hospital Universitario San Cecilio | Rozas-Moreno P.,Hospital General Of Ciudad Real | Reyes-Garcia R.,Hospital Universitario San Cecilio | And 5 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2012

Context: Diabetes mellitus is a risk factor for osteoporotic fractures. Sclerostin is an inhibitor of bone formation. However, there are no data about sclerostin levels in type 2 diabetes mellitus (T2DM). Objectives: The aims were to evaluate serum sclerostin in T2DM patients and to analyze its relationship with bone metabolism. Design, Setting, and Patients: This was a cross-sectional study. We compared serum sclerostin in the T2DM group (n = 74) and control group (n = 50), and we analyzed its relationship with calciotropic hormones, bone turnover markers, bone mineral density (BMD), and morphometric vertebral fractures. Results: Sclerostin levels were significantly higher in T2DM patients than control subjects (P <0.001) and in T2DM males than in T2DM females (P < 0.001). Serum sclerostin was positively correlated with age in males T2DM (P = 0.031). In linear regression analysis, gender, study group, and age were predictive of sclerostin levels (P < 0.05). Sclerostin concentrations were positively associated with duration of T2DM (P=0.064) and glycated hemoglobin (P=0.074) independently of age in T2DM patients. Sclerostin was inversely related to bone turnover markers (P < 0.05) and positively related to lumbar spine, femoral neck, and total hip BMD (P < 0.05) in the T2DM group. Sclerostin was significantly lower in osteoporotic than nonosteoporotic patients with T2DM (P = 0.048). Conclusions: Circulating sclerostin is increased in T2DM independently of gender and age. Serum sclerostin is also correlated with duration of T2DM, glycated hemoglobin, bone turnover markers, and BMD in T2DM patients. Additional studies are needed to evaluate the role of sclerostin on bone metabolism in this population. Copyright © 2012 by The Endocrine Society.


Garcia-Delgado M.,Hospital Universitario Virgen Of Las Nieves | Navarrete-Sanchez I.,Hospital Universitario Virgen Of Las Nieves | Colmenero M.,Hospital Universitario San Cecilio
Current Opinion in Anaesthesiology | Year: 2014

PURPOSE OF REVIEW: To provide an update of research findings on the mechanisms underlying respiratory complications after cardiac surgery, especially acute respiratory distress syndrome, transfusion-related lung injury and ventilation-associated pneumonia. The article will review some of the preventive and therapeutic measures that can be implemented to reduce these complications, focusing on the use of protective invasive ventilation and postextubation noninvasive ventilation. RECENT FINDINGS: The development of postoperative pulmonary complications is related to various perioperative factors. The most effective preventive measures are a correct preoperative preparation and an uneventful surgery. The implementation of nosocomial pneumonia prevention bundles, or early extubation in a fast-track program, has proven to be effective in reducing the complication rate. The application of protective invasive ventilation, with low tidal volumes, has been found to reduce lung injury and mortality in patients with lung injury or healthy lungs. The use of noninvasive ventilation as a preventive postextubation approach in patients at risk and rescue noninvasive ventilation in those developing respiratory failure remains under debate and is subject to ongoing research. SUMMARY: Postoperative pulmonary complications are common, but severe complications are infrequent. Their reduction requires measures to prevent infection and mechanical ventilation-associated lung injury through the use of low tidal volumes and early extubation. Noninvasive ventilation after extubation can be utilized to avoid reintubation and the associated increased morbidity and mortality. However, noninvasive ventilation should be done under rigorous conditions and by following strict criteria. © 2014 Wolter Kluwer Health | Lippincott Williams & Wilkins.


Rabe E.,University of Bonn | Guex J.-J.,32 Bd Dubouchage | Puskas A.,University of Medicine and Pharmacy of Targu Mures | Fernandez Quesada F.,Hospital Universitario San Cecilio
International Angiology | Year: 2012

Aim. The Vein Consult Program is an international, observational, prospective survey aiming to collect global epidemiological data on chronic venous disorders (CVD) based on the CEAP classification, and to identify CVD management worldwide. The survey was organized within the framework of ordinary consultations, with general practitioners (GPs) properly trained on the use of the CEAP classification. Methods. Screening for CVD was to be performed by enrolling in the survey all consecutive outpatients >18 years whatever the reason for consultation, to record patient's data and classify them according to the CEAP, from the stage C0s to C6. Results. The program enrolled 6232 GPs and 91545 subjects were analysed. Their mean age was 50.6±16.9 years, younger patients being in the Middle East and older ones in Europe, and the proportion of women was higher than that of men. The worldwide prevalence of CVD was 83.6%: 63.9% of the subjects ranging C1 to C6, and 19.7% being COs subjects. COs patients were more frequently men whatever the age and the geographical zone. C1-C3 appeared to be more frequent among women whatever the country but the rate of severe stages (C4-C6) did not differ between men and women. GPs consider CVD subjects as patients eligible to specialist referral beginning from C2 but some geographical disparities were observed. Conclusion. The VCP survey provides reliable results on CVD global epidemiology and shows that CVD affects a significant part of the populations worldwide, underlining the importance of adequate screening for CVD and training of both GPs and specialist physicians.


Perinatal mortality has significantly decreased over the last decades. Low birth weight and prematurity are amongst the strongest predictors of neonatal death. The main objective is to analyze the evolution of perinatal mortality and its causes in newborn infants with a birth weight of less than 1000 grams over the last 20 years (1991-2010). Observational, descriptive, longitudinal and ecological study. A total of 264 infants weighing less than 1000 g out of a total of 56 024 births during the study period. Different specific perinatal mortality rates by weight were calculated. The Spearman's Rho correlation coefficient was applied to assess the relationship between mortality rates and years of study, and ANOVA and Mann-Whitney test were used to compare five-year periods and ten-year periods, respectively. There were 131 perinatal deaths, 82 stillbirths and 49 early neonatal deaths; 64.1% of them occurred before 27 weeks of gestation. Only the fetal mortality rate was statistically significant, although perinatal mortality showed a downward trend, without reaching significance. The main immediate causes of death were extreme prematurity, intrauterine hypoxia and infection. The underlying causes related to death in this group of newborn infants were infection caused by premature rupture of membranes, maternal hypertension, uncontrollable preterm labor and twin pregnancy. The reduction in mortality rates in this group of newborn infants is undergoing a slowdown.


Poveda E.,Inibic Complejo Hospitalario Universitario Of runa | Garcia F.,Hospital Universitario San Cecilio
Enfermedades Infecciosas y Microbiologia Clinica | Year: 2013

Telaprevir is an extremely potent antiviral drug. However, as with other direct-acting antiviral agents against the hepatitis C virus (HCV), this potency can be compromised by the rapid emergence of resistance mutations. This phenomenon is favored by the high rate of HCV replication, the lack of corrective activity to HCV polymerase errors, a low genetic barrier to resistance, and poor treatment adherence. Like other HCV protease inhibitors, telaprevir has a low genetic barrier to resistance. Phase II/III clinical trials (ADVANCE, ILLUMINATE and REALIZE) have characterized resistance to telaprevir in combination with pegylated interferon and ribavirin both genotypically and phenotypically. Mutations are selected mainly in positions 36, 54, 55, 155 and 156. The resistance profile depends on the genetic subtype of HCV, with selection of mutations in positions 36 and 155 for subtype 1a and in positions 36, 54, 55 and 156 for subtype 1b. The V36M+R155K and A156F/T/V variants confer a high degree of resistance (>25-fold increase), while the impact on resistance of other mutations such as V36A/G/M, T54A/S, R155G/K/M/T and A156S is lower (3-25- fold increase). The presence of polymorphisms or mutations associated with telaprevir resistance is very low (< 1%), especially for mutations with a higher impact on resistance. There is a high degree of cross resistance among protease inhibitors. However, the rapid reversion of telaprevir resistance mutations after the end of treatment could allow the use of "recycling" strategies with protease inhibitors. © 2013 Elsevier España, S.L. All rights reserved.


Cortes-Berdonces M.,Hospital Universitario San Cecilio
Nutrición hospitalaria : organo oficial de la Sociedad Española de Nutrición Parenteral y Enteral | Year: 2012

Anemia is a common condition among surgical and critically ill patients and it is usually treated with allogenic blood transfusion (ABT). As ABT is associated with increased morbidity and mortality, alternative therapies for anemia in these patients are actively investigated. To asses the potential usefulness of intravenous iron therapy in critically-ill or surgical patients with anemia. Methods: Review of published papers with intravenous iron in these patients. Bibliographical search on database Medline (www.ncvi.nlm.nih.gov). Treatment with intravenous iron is not sufficient to treat the anemia of critically ill patients. Its association with erythropoietin (EPO) may have an effect on the rate of ABT, but it has not been shown to improve morbidity, mortality or length of hospital stay. In gastrointestinal or trauma surgery there is no evidence to support the routine preoperative treatment with intravenous iron, although it may be beneficial when it is used with erythropoietin. Intravenous iron alone or in combination with EPO in the postoperative period has not been proved useful for rapid correction of anemia, reduction of hospital stay or mortality.


Morales-Santana S.,Hospital Universitario San Cecilio | Morales-Santana S.,Proteomic Research Service | Garcia-Fontana B.,Hospital Universitario San Cecilio | Garcia-Martin A.,Hospital Universitario San Cecilio | And 4 more authors.
Diabetes Care | Year: 2013

OBJECTIVE - Wnt/β-catenin signaling is related to the pathogenesis of several diseases. Sclerostin is an inhibitor of Wnt/β-catenin signaling. However, there are few data regarding the sclerostin levels and vascular disease. Our aim was to examine the relationship between serum sclerostin and atherosclerotic disease (AD) in type 2 diabetes mellitus (T2DM). RESEARCH DESIGN ANDMETHODS - We performed a cross-sectional study including 78 T2DM patients (45.3% females, mean age 59 ± 5.7 years; 54.7% males, 57.4 ± 6.7 years). RESULTS - Serum sclerostin concentrations of T2DM patients in the AD group were significantly higher than in the non-AD group (P = 0.006). For each increase of 1 pmol/L in sclerostin level, there was a 4% increase of the risk of AD in T2DM patients. A concentration of ≥42.3 pmol/L showed a sensitivity of 69% and a specificity of 54.8% to detect an increased risk of AD. In males, sclerostin levels were higher in those with AD (P = 0.04), abnormal intima-media thickness (IMT) (P = 0.004), carotid plaques (P < 0.001), and aortic calcification (P < 0.001). In females, higher levels of sclerostin were related to abnormal IMT ( P = 0.03) and aortic calcifications (P = 0.004). Homocysteine (β = 0.319 [95% CI 0.561-2.586], P = 0.003) and IMT (β = 0.330 [14.237-67.693], P = 0.003) were positively correlated with sclerostin. CONCLUSIONS - Circulating sclerostin is increased in T2DM patients with atherosclerotic lesions. Although the sample size of our study was small, these data suggest that sclerostin levels could be a major modulator of Wnt signaling in AD with implications in T2DM patients. © 2013 by the American Diabetes Association.

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