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Garrido-Sanchez L.,Hospital Universitari Joan | Garcia-Fuentes E.,Fundacion IMABIS | Garcia-Fuentes E.,CIBER ISCIII | Fernandez-Garcia D.,CIBER ISCIII | And 9 more authors.
PLoS ONE | Year: 2012

Objective: Zinc-α 2 glycoprotein (ZAG) stimulates lipid loss by adipocytes and may be involved in the regulation of adipose tissue metabolism. However, to date no studies have been made in the most extreme of obesity. The aims of this study are to analyze ZAG expression levels in adipose tissue from morbidly obese patients, and their relationship with lipogenic and lipolytic genes and with insulin resistance (IR). Methods: mRNA expression levels of PPARγ, IRS-1, IRS-2, lipogenic and lipolytic genes and ZAG were quantified in visceral (VAT) and subcutaneous adipose tissue (SAT) of 25 nondiabetic morbidly obese patients, 11 with low IR and 14 with high IR. Plasma ZAG was also analyzed. Results: The morbidly obese patients with low IR had a higher VAT ZAG expression as compared with the patients with high IR (p = 0.023). In the patients with low IR, the VAT ZAG expression was greater than that in SAT (p = 0.009). ZAG expression correlated between SAT and VAT (r = 0.709, p<0.001). VAT ZAG expression was mainly predicted by insulin, HOMA-IR, plasma adiponectin and expression of adiponectin and ACSS2. SAT ZAG expression was only predicted by expression of ATGL. Conclusions: ZAG could be involved in modulating lipid metabolism in adipose tissue and is associated with insulin resistance. These findings suggest that ZAG may be a useful target in obesity and related disorders, such as diabetes. © 2012 Garrido-Sánchez et al.


Garrido-Sanchez L.,Hospital Universitari Joan | Vendrell J.,Hospital Universitari Joan | Fernandez-Garcia D.,Hospital Clinico Virgen Of La Victoria | Fernandez-Garcia D.,CIBER ISCIII | And 7 more authors.
PLoS ONE | Year: 2012

Objective: De novo lipogenesis is involved in fatty acid biosynthesis and could be involved in the regulation of the triglyceride storage capacity of adipose tissue. However, the association between lipogenic and lipolytic genes and the evolution of morbidly obese subjects after bariatric surgery remains unknown. In this prospective study we analyze the association between the improvement in the morbidly obese patients as a result of bariatric surgery and the basal expression of lipogenic and lipolytic genes. Methods: We study 23 non diabetic morbidly obese patients who were studied before and 7 months after bariatric surgery. Also, we analyze the relative basal mRNA expression levels of lipogenic and lipolytic genes in epiploic visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT). Results: When the basal acetyl-CoA carboxylase 1 (ACC1), acetyl-CoA synthetase 2 (ACSS2) and ATP citrate lyase (ACL) expression in SAT was below percentile-50, there was a greater decrease in weight (P = 0.006, P = 0.034, P = 0.026), body mass index (P = 0.008, P = 0.033, P = 0.034) and hip circumference (P = 0.033, P = 0.021, P = 0.083) after bariatric surgery. In VAT, when the basal ACSS2 expression was below percentile-50, there was a greater decrease in hip circumference (P = 0.006). After adjusting for confounding variables in logistic regression models, only the morbidly obese patients with SAT or VAT ACSS2 expression≥P50 before bariatric surgery had a lower percentage hip circumference loss (


Soriguer F.,Hospital Regional Universitario Carlos Haya | Soriguer F.,CIBER ISCIII | Gutierrez-Repiso C.,Fundacion IMABIS | Gonzalez-Romero S.,Hospital Regional Universitario Carlos Haya | And 9 more authors.
Clinical Nutrition | Year: 2011

Background & aims: The importance of milk intake to the supply of dietary iodine is not fully known. We therefore undertook a study in Spain of the iodine concentration in cow's milk and the impact of the frequency of milk consumption on urinary iodine concentrations in three study populations. Methods: We studied the iodine concentration in 362 samples of milk from 45 commercial brands and compared it with the milk iodine status in studies undertaken 17 years earlier. The epidemiologic studies were performed in three different places in the south of Spain: two in school-age children (N = 757 and N = 1205 children) and one in adults (N = 1051). A milk consumption questionnaire was given and urinary iodine concentrations measured. Results: The mean concentration of iodine in the milk rose from 1991 (117 ± 37 μg/L) to 2008 (259 ± 58 μg/L) (P < 0.001). The iodine concentration was greater in skimmed milk (273 ± 52 μg/L) than in semi-skimmed milk (254 ± 57 μg/L) or whole milk (251 ± 61 μg/L) (P < 0.0001). The winter samples had a greater concentration of iodine (270 ± 55 μg/L) than the summer samples (247 ± 58 μg/L) (P < 0.0001), independently of the type of milk. The urinary iodine concentrations in all three epidemiologic studies were significantly associated with the frequency of milk intake. Conclusions: The concentration of iodine in cow's milk has risen over recent years, and it is higher in skimmed milk. The results also show that cow's milk is a relevant source of dietary iodine. © 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism.


Garcia-Fuentes E.,CIBER ISCIII | Murri M.,Fundacion IMABIS | Garrido-Sanchez L.,CIBER ISCIII | Garcia-Serrano S.,CIBER ISCIII | And 5 more authors.
Obesity | Year: 2010

Peroxisome proliferator-activated receptor-γ (PPARγ) may play a protective role in the regulation of vascular function, partly mediated by its effects on superoxide dismutase (SOD). The aim of this study was to determine the association between PPARγ expression in peripheral blood mononuclear cells (PBMCs) and SOD activity in morbidly obese persons with varying degrees of insulin resistance (IR). We studied in 10 morbidly obese persons (five with no IR and five with high IR) the effect of a high-fat meal on the plasma activity of various antioxidant enzymes and the mRNA expression of PPARγ in PBMC. The high-fat meal resulted in a significant decrease in plasma SOD activity, glutathione reductase (GSH-Rd) activity, and mRNA expression of PPARγ only in the group of morbidly obese persons with high IR. PPARγ expression after the high-fat meal correlated with the IR levels (r = 0.803, P = 0.009) and the plasma SOD activity (r = 0.903, P = 0.001). Likewise, the reduction in PPARγ expression correlated with the increase in free fatty acids (FFA) (r = 0.733, P = 0.016). In conclusion, the decreased expression of PPARγ in PBMC in morbidly obese persons after a high-fat meal was associated with the state of IR, the plasma SOD activity, and the changes in the concentration of FFA. © 2010 The Obesity Society.


Reguero L.,University of the Basque Country | Puente N.,University of the Basque Country | Elezgarai I.,University of the Basque Country | Mendizabal-Zubiaga J.,University of the Basque Country | And 7 more authors.
PLoS ONE | Year: 2011

Background: Type-1 cannabinoid receptors (CB 1R) are enriched in the hypothalamus, particularly in the ventromedial hypothalamic nucleus (VMH) that participates in homeostatic and behavioral functions including food intake. Although CB 1R activation modulates excitatory and inhibitory synaptic transmission in the brain, CB 1R contribution to the molecular architecture of the excitatory and inhibitory synaptic terminals in the VMH is not known. Therefore, the aim of this study was to investigate the precise subcellular distribution of CB 1R in the VMH to better understand the modulation exerted by the endocannabinoid system on the complex brain circuitries converging into this nucleus. Methodology/Principal Findings: Light and electron microscopy techniques were used to analyze CB 1R distribution in the VMH of CB 1R-WT, CB 1R-KO and conditional mutant mice bearing a selective deletion of CB 1R in cortical glutamatergic (Glu-CB 1R-KO) or GABAergic neurons (GABA-CB 1R-KO). At light microscopy, CB 1R immunolabeling was observed in the VMH of CB 1R-WT and Glu-CB 1R-KO animals, being remarkably reduced in GABA-CB 1R-KO mice. In the electron microscope, CB 1R appeared in membranes of both glutamatergic and GABAergic terminals/preterminals. There was no significant difference in the percentage of CB 1R immunopositive profiles and CB 1R density in terminals making asymmetric or symmetric synapses in CB 1R-WT mice. Furthermore, the proportion of CB 1R immunopositive terminals/preterminals in CB 1R-WT and Glu-CB 1R-KO mice was reduced in GABA-CB 1R-KO mutants. CB 1R density was similar in all animal conditions. Finally, the percentage of CB 1R labeled boutons making asymmetric synapses slightly decreased in Glu-CB 1R-KO mutants relative to CB 1R-WT mice, indicating that CB 1R was distributed in cortical and subcortical excitatory synaptic terminals. Conclusions/Significance: Our anatomical results support the idea that the VMH is a relevant hub candidate in the endocannabinoid-mediated modulation of the excitatory and inhibitory neurotransmission of cortical and subcortical pathways regulating essential hypothalamic functions for the individual's survival such as the feeding behavior. © 2011 Reguero et al.


Conejo Ceron S.,Fundacion IMABIS | Moreno Peral P.,Fundacion IMABIS | Morales Asencio J.M.,University of Malaga | Alot Montes A.,Hospital Regional Universitario Carlos Haya | And 5 more authors.
Anales del Sistema Sanitario de Navarra | Year: 2014

Methodology. This was a qualitative study, based on five focus groups with mental health professionals (psychiatrists, psychologists, nurses, general practitioners, monitors and social workers) from Carlos Haya Hospital in Malaga, Spain. A content analysis was performed on the transcriptions by three independent researchers.Background. Over the years, a number of definitions of severe mental illness (SMI) have been proposed and substantial controversy about the definition still remains. The aim of this study was to evaluate the views of a group of mental health professionals on the appropriate criteria for defining SMI.Results. The professionals agreed that a certain degree of dysfunctionality must be present for a definition of SMI. There was some disagreement between the different categories of professionals regarding the inclusion of dimensions such as diagnosis, family and social support, use of healthcare resources and duration of the illness as necessary and sufficient criteria for the definition of SMI. From the professionals’ discourse, some personal patient variables such as age of onset of illness, lack of insight and level of education emerged as relevant for the definition of SMI.Conclusions. Apart from the dimensions considered in the literature, the interviewed mental health professionals discussed other criteria that could be taken into account in the definition of SMI. Perceptions differ between categories of professional and work settings in which they operate. © 2014, Gobierno de Navarra. All rights reserved.


Garrido-Sanchez L.,CIBER ISCIII | Murri M.,Fundacion Imabis | Murri M.,Hospital Clnico Virgen Of La Victoria | Rivas-Becerra J.,Hospital Clnico Virgen Of La Victoria | And 6 more authors.
Surgery for Obesity and Related Diseases | Year: 2012

Background: Obesity is very often accompanied by other diseases, with the most common type 2 diabetes mellitus and cardiovascular complications. Bariatric surgery is the most effective strategy for treating morbidly obese patients. We evaluated the metabolic changes that occur in the early stage after 2 types of bariatric surgery, biliopancreatic diversion of Scopinaro (BPD) and sleeve gastrectomy (SG), in morbidly obese patients. Methods: The study was undertaken in 31 nondiabetic morbidly obese patients (7 men and 24 women). Of the 31 patients, 18 underwent BPD and 13 underwent SG. All patients were examined before bariatric surgery (baseline) and at 15, 30, 45, and 90 days postoperatively. Results: Significant improvement occurred in the anthropometric variables after the 2 types of bariatric surgery, without significant differences between the 2 types of interventions. In patients undergoing BPD, the serum glucose, cholesterol, triglycerides, high-density lipoprotein cholesterol, and free fatty acids were significantly reduced. The changes that occurred in these biochemical variables after SG were not significant. Insulin resistance decreased significantly during the 90 days after surgery, with the greatest decrease at 15 days. However, in the patients who underwent SG, insulin resistance worsened at 15 days and later diminished. Conclusion: The results of the present study have shown that the surgical technique that excludes the duodenum (i.e., BPD) has immediate postoperative changes in the degree of insulin resistance in morbidly obese patients compared to those techniques that do not exclude the duodenum (i.e., SG). © 2012 American Society for Metabolic and Bariatric Surgery. All rights reserved.


Karlsson J.,Fundacion IMABIS | Trelles O.,University of Malaga
Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) | Year: 2012

It becomes increasingly important to support automated service discovering and composition due to the growing number of Web Services and data types in bioinformatics and biomedicine. jORCA is a user-friendly desktop client which is able to discover and invoke Web Services from different metadata repositories for services. This paper demonstrates the usefulness of jORCA for service composition by recreating a previously published workflow, starting with the discovery of data types, service composition (workflow generation) and refinement; to enactment, monitoring and visualization of results. The system has been exhaustively tested and documented and is freely available at http://www.bitlab-es.com/jorca . © 2012 Springer-Verlag.


PubMed | Hospital Regional Universitario Carlos Haya, Fundacion IMABIS, Hospital Of Riotinto, Hospital General and CIBER ISCIII
Type: Journal Article | Journal: The British journal of nutrition | Year: 2014

Little information is available as to whether doses of iodide similar to those recommended in clinical practice for the prevention of iodine deficiency in pregnant women affect thyroid function. The aim of the present study was to analyse whether doses of iodide can affect thyroid function in adults, and evaluate its effect on plasma markers of oxidative stress, inflammation and acute-phase proteins. A total of thirty healthy volunteers (ten men and twenty women) with normal thyroid function were randomly assigned to three groups (n 10). Each group received a daily dose of 100, 200 or 300g of iodide in the form of KI for 6 months. Free tetraiodothyronine (FT4) levels at day 60 of the study were higher in the groups treated with 200 and 300g (P=001), and correlated with the increase in urinary iodine (r 050, P=0007). This correlation lost its significance after adjustment for the baseline FT4. The baseline urinary iodine and FT4 correlated positively with the baseline glutathione peroxidase. On day 60, urinary iodine correlated with C-reactive protein (r 0461, P=0018), and free triiodothyronine correlated with IL-6 (r -0429, P=0025). On day 60, the changes produced in urinary iodine correlated significantly with the changes produced in 1-antitrypsin (r 0475, P=0014) and ceruloplasmin (r 0599, P=0001). The changes in thyroid-stimulating hormone correlated significantly with the changes in 1-antitrypsin (r -0521, P=0005) and ceruloplasmin (r -0459, P=0016). In conclusion, the administration of an iodide supplement between 100 and 300g/d did not modify thyroid function in a population with adequate iodine intake. The results also showed a slight anti-inflammatory and antioxidative action of iodide.


Gervasini G.,University of Extremadura | Agundez J.A.G.,University of Extremadura | Garcia-Menaya J.,Infanta Cristina University Hospital | Martinez C.,University of Extremadura | And 5 more authors.
Allergy: European Journal of Allergy and Clinical Immunology | Year: 2010

Background: Nonsynonymous polymorphisms in genes coding for histamine-metabolizing enzymes, diamine oxidase and histamine N-methyltransferase are related to the risk of developing allergic diseases. The role of polymorphisms in the histidine decarboxylase gene remains unexplored. The objective of this study is to identify novel polymorphisms in the human histidine decarboxylase gene and to analyse the clinical association of nonsynonymous polymorphisms with rhinitis. Methods: We performed a single-strand conformational polymorphism analysis of the histidine decarboxylase gene sequence. The presence of two nonsynonymous polymorphisms Thr31Met (rs17740607) and Glu644Asp (rs2073440) was analysed in 442 unrelated patients with allergic rhinitis, 233 of whom also had asthma, and in 486 healthy subjects. Results: We observed three novel polymorphisms designated as ss50402829, ss50402830 and ss50402831-(rs17740607) with allele frequencies=0.005, 0.208 and 0.073, respectively. Statistically significant differences were observed for the histidine decarboxylase Glu644Asp (rs2073440) polymorphism, with OR (95% CI) values for homozygous carriers of the Glu644 allele equal to 3.12 (1.75-5.56, P<0.00005) for all patients, 3.38 (1.54-7.44, P=0.002) for patients with rhinitis alone, and 2.92 (1.43-5.95), P=0.003 for patients with rhinitis+asthma, when compared with healthy controls. A significant Glu644 gene-dose effect was observed for overall patients (P=0.0001), for patients with rhinitis alone (P=0.005) and for patients with rhinitis+asthma (P=0.010). Conclusions: The HDC allele Glu644 in homozygosity increases the risk of developing rhinitis in the studied population. This adds to increasing evidence supporting a prominent role of genetic variations related to histamine homeostasis in the risk to develop allergic diseases. © 2010 John Wiley & Sons A/S.

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