Vila-Bedmar R.,Complutense University of Madrid |
Vila-Bedmar R.,CIBER ISCIII |
Fernandez-Veledo S.,Complutense University of Madrid |
Fernandez-Veledo S.,CIBER ISCIII |
And 2 more authors.
Archives of Physiology and Biochemistry | Year: 2011
Until quite recently, brown adipose tissue was considered of metabolic significance only in small mammals and human newborns, since it was thought to disappear rapidly after birth in humans. However, nowadays this tissue is known to play a role in the regulation of energy balance not only in rodents, but also in humans. In this review we highlight new features regarding brown adipose tissue origin and function and revise old paradigms about brown adipocyte differentiation. © 2011 Informa UK, Ltd.
Fernandez-Real J.M.,University of Girona |
Del Pulgar S.P.,University of Girona |
Del Pulgar S.P.,University Hospital of Tarragona Joan |
Del Pulgar S.P.,Barcelona Institute for Research in Biomedicine |
And 17 more authors.
Diabetes | Year: 2011
OBJECTIVE - The study objective was to evaluate the possible role of the macrophage molecule CD14 in insulin resistance. RESEARCH DESIGN AND METHODS - The effects of recombinant human soluble CD14 (rh-sCD14) on insulin sensitivity (clamp procedure) and adipose tissue gene expression were evaluated in wild-type (WT) mice, high fat-fed mice, ob/ob mice, and CD14 knockout (KO) mice. We also studied WT mice grafted with bone marrow stem cells from WT donor mice and CD14 KO mice. Finally, CD14 was evaluated in human adipose tissue and during differentiation of human preadipocytes. RESULTS - rh-sCD14 led to increased insulin action in WT mice, high-fat-fed mice, and ob/ob mice, but not in CD14 KO mice, in parallel to a marked change in the expression of 3,479 genes in adipose tissue. The changes in gene families related to lipid metabolism were most remarkable. WT mice grafted with bone marrow stem cells from WT donor mice became insulin resistant after a high-fat diet. Conversely, WT mice grafted with cells from CD14 KO mice resisted the occurrence of insulin resistance in parallel to decreased mesenteric adipose tissue inflammatory gene expression. Glucose intolerance did not worsen in CD14 KO mice grafted with bone marrow stem cells from high fat-fed WT mice when compared with recipient KO mice grafted with cells from CD14 KO donor mice. CD14 gene expression was increased in whole adipose tissue and adipocytes from obese humans and further increased after tumor necrosis factor-a. CONCLUSIONS - CD14 modulates adipose tissue inflammatory activity and insulin resistance. © 2011 by the American Diabetes Association.
PubMed | University Hospital October 12, Studies Institute of Health science of Castilla and Leon IESCYL, University of Valencia, Gregorio Maranon Hospital and 6 more.
Type: Journal Article | Journal: British journal of haematology | Year: 2016
The introduction of Rituximab has improved the outcome and survival rates of Burkitt lymphoma (BL). However, early relapse and refractoriness are current limitations of BL treatment and new biological factors affecting the outcome of these patients have not been explored. This study aimed to identify the presence of genomic changes that could predict the response to new therapies in BL. Forty adolescent and adult BL patients treated with the Dose-Intensive Chemotherapy Including Rituximab (Burkimab) protocol (Spanish Programme for the Study and Treatment of Haematological Malignancies; PETHEMA) were analysed using array-based comparative genomic hybridization (CGH). In addition, the presence of TP53, TCF3 (E2A), ID3 and GNA13 mutations was assessed by next-generation sequencing (NGS). Ninety-seven per cent of the patients harboured genomic imbalances. Losses on 11q, 13q, 15q or 17p were associated with a poor response to Burkimab therapy (P=0038), shorter progression-free survival (PFS; P=0007) and overall survival (OS; P=0009). The integrative analysis of array-CGH and NGS showed that 263% (5/19) and 368% (7/19) of patients carried alterations in the TP53 and TCF3 genes, respectively. TP53 alterations were associated with shorter PFS (P=0011) while TCF3 alterations were associated with shorter OS (P=0032). Genetic studies could be used for risk stratification of BL patients treated with the Burkimab protocol.
Ibanez R.,Catalan Institute of Oncology ICO |
Felez-Sanchez M.,Catalan Institute of Oncology ICO |
Felez-Sanchez M.,Lhospitalet Of Llobregat |
Godinez J.M.,Lhospitalet Of Llobregat |
And 16 more authors.
Journal of Clinical Microbiology | Year: 2014
In Catalonia, a screening protocol for cervical cancer, including human papillomavirus (HPV) DNA testing using the Digene Hybrid Capture 2 (HC2) assay, was implemented in 2006. In order to monitor interlaboratory reproducibility, a proficiency testing (PT) survey of the HPV samples was launched in 2008. The aim of this study was to explore the repeatability of the HC2 assay's performance. Participating laboratories provided 20 samples annually, 5 randomly chosen samples from each of the following relative light unit (RLU) intervals: <0.5, 0.5 to 0.99, 1 to 9.99, and ≥10. Kappa statistics were used to determine the agreement levels between the original and the PT readings. The nature and origin of the discrepant results were calculated by bootstrapping. A total of 946 specimens were retested. The kappa values were 0.91 for positive/negative categorical classification and 0.79 for the four RLU intervals studied. Sample retesting yielded systematically lower RLU values than the original test (P < 0.005), independently of the time elapsed between the two determinations (median, 53 days), possibly due to freeze-thaw cycles. The probability for a sample to show clinically discrepant results upon retesting was a function of the RLU value; samples with RLU values in the 0.5 to 5 interval showed 10.80% probability to yield discrepant results (95% confidence interval [CI], 7.86 to 14.33) compared to 0.85% probability for samples outside this interval (95% CI, 0.17 to 1.69). Globally, the HC2 assay shows high interlaboratory concordance. We have identified differential confidence thresholds and suggested the guidelines for interlaboratory PT in the future, as analytical quality assessment of HPV DNA detection remains a central component of the screening program for cervical cancer prevention. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
Ibanez R.,199 203Lhospitalet Of Llobregat |
Moreno-Crespi J.,University of Girona |
Sarda M.,Hospital Consortium of Vic |
Autonell J.,Hospital Consortium of Vic |
And 11 more authors.
BMC Infectious Diseases | Year: 2012
Background: A protocol for cervical cancer screening among sexually active women 25 to 65 years of age was introduced in 2006 in Catalonia, Spain to increase coverage and to recommend a 3-year-interval between screening cytology. In addition, Human Papillomavirus (HPV) was offered as a triage test for women with a diagnosis of atypical squamous cells of undetermined significance (ASC-US). HPV testing was recommended within 3 months of ASC-US diagnosis. According to protocol, HPV negative women were referred to regular screening including a cytological exam every 3 years while HPV positive women were referred to colposcopy and closer follow-up. We evaluated the implementation of the protocol and the prediction of HPV testing as a triage tool for cervical intraepithelial lesions grade two or worse (CIN2+) in women with a cytological diagnosis of ASC-US.Methods: During 2007-08 a total of 611 women from five reference laboratories in Catalonia with a novel diagnosis of ASC-US were referred for high risk HPV (hrHPV) triage using high risk Hybrid Capture version 2. Using routine record linkage data, women were followed for 3 years to evaluate hrHPV testing efficacy for predicting CIN2+ cases. Logistic regression analysis was used to estimate the odds ratio for CIN2 +.Results: Among the 611 women diagnosed with ASC-US, 493 (80.7%) had at least one follow-up visit during the study period. hrHPV was detected in 48.3% of the women at study entry (mean age 35.2 years). hrHPV positivity decreased with increasing age from 72.6% among women younger than 25 years to 31.6% in women older than 54 years (p < 0.01).At the end of the 3 years follow-up period, 37 women with a diagnosis of CIN2+ (18 CIN2, 16 CIN3, 2 cancers, and 1 with high squamous intraepithelial lesions -HSIL) were identified and all but one had a hrHPV positive test at study entry. Sensitivity to detect CIN2+ of hrHPV was 97.2% (95%confidence interval (CI) = 85.5-99.9) and specificity was 68.3% (95%CI = 63.1-73.2). The odds ratio for CIN2+ was 45.3 (95% CI: 6.2-333.0), when among ASC-US hrHPV positive women were compared to ASC-US hrHPV negative women.Conclusions: Triage of ASC-US with hrHPV testing showed a high sensitivity for the detection of CIN2+ and a high negative predictive value after 3 years of follow-up. The results of this study are in line with the current guidelines for triage of women with ASC-US in the target age range of 25-65. Non adherence to guidelines will lead to unnecessary medical interventions. Further investigation is needed to improve specificity of ASC-US triage. © 2012 Ibáñez et al; licensee BioMed Central Ltd.
Broch M.,CIBER ISCIII |
Broch M.,Rovira i Virgili University |
Ramirez R.,University Hospital of Tarragona Joan |
Auguet M.T.,CIBER ISCIII |
And 9 more authors.
Physiological Research | Year: 2010
Obesity is linked to a low-level chronic inflammatory state that may contribute to the development of associated metabolic complications. Retinol-binding protein 4 (RBP4) is an adipokine associated with parameters of obesity including insulin resistance indices, body mass index, waist circumference, lipid profile, and recently, with circulating inflammatory factors. Due to the infiltration of adipose tissue in obesity by macrophages derived from circulating monocytes and, on the other hand, the existence of a close genetic relationship between adipocytes and macrophages, we decided to examine if RBP4 is expressed in monocytes and/or primary human macrophages. While we did not detect expression of RBP4 in undifferentiated monocytes, RBP4 expression became evident during the differentiation of monocytes into macrophages and was highest in differentiated macrophages. Once we demonstrated the expression of RBP4 in macrophages, we checked if RBP4 expression could be regulated by inflammatory stimuli such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), or the endotoxin lipopolysaccharide (LPS). We observed that while RBP4 expression was strongly inhibited by TNF-α and LPS, it was not affected by IL-6. Our results highlight the complexity behind the regulation of this adipokine and demonstrate that RBP4 expression in macrophages could be modulated by inflammatory stimuli. © 2010 Institute of Physiology v.v.i., Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Hahn K.,German Cancer Research Center |
Miranda M.,CIBER ISCIII |
Miranda M.,University Hospital of Tarragona Joan |
Francis V.A.,German Cancer Research Center |
And 9 more authors.
Cell Metabolism | Year: 2010
The insulin/TOR signaling pathway plays a crucial role in animal homeostasis, sensing nutrient status to regulate organismal growth and metabolism. We identify here the Drosophila B′ regulatory subunit of PP2A (PP2A-B′) as a novel, conserved component of the insulin pathway that specifically targets the PP2A holoenzyme to dephosphorylate S6K. PP2A-B′ knockout flies have elevated S6K phosphorylation and exhibit phenotypes typical of elevated insulin signaling such as reduced total body triglycerides and reduced longevity. We show that PP2A-B′ interacts with S6K both physically and genetically. The human homolog of PP2A-B′, PPP2R5C, also counteracts S6K1 phosphorylation, indicating a conserved mechanism in mammals. Since S6K affects development of cancer and metabolic disease, our data identify PPP2R5C as a novel factor of potential medical relevance. © 2010 Elsevier Inc.
Esteve E.,Institute Dinvestigacio Biomedica Of Girona |
Esteve E.,CIBER ISCIII |
Esteve E.,Institute Salud Carlos III |
Castro A.,Institute Dinvestigacio Biomedica Of Girona |
And 12 more authors.
Thrombosis and Haemostasis | Year: 2010
Bactericidal/permeability-increasing protein (BPI), a major constituent of neutrophils that possesses anti-inflammatory properties, shows a structure similar to some proteins implicated in lipid metabolism. We evaluated circulating BPI as a biomarker of endothelial function and lipid metabolism. Circulating BPI concentrations (ELISA) and serum lipids were measured in 202 Caucasian non-smoking men. In a subgroup of 91 consecutive subjects brachial vascular reactivity (high resolution external ultrasound) was assessed. Plasma BPI concentrations were positively associated with total cholesterol (TC), LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C) (r= 0.203, 0.204 and 0.18; all p<0.05, respectively). In a multiple linear regression analysis, BPI levels were independent contributors to the variance of HDL-C, total cholesterol and LDL-cholesterol after adjusting for age, body mass index and glucose tolerance status. Plasma BPI concentration correlated positively with endothelium- dependent vasodilatation (r=0.277; p<0.05) and HDL-C (r=0.36; p<0.05) in subjects with normal glucose tolerance. In conclusion, circulating BPI could constitute a biomarker of lipid metabolism in subjects with normal glucose tolerance and could help to identify those subjects with preserved endothelial function. © Schattauer 2010.
Aguilar V.,Montpellier University |
Annicotte J.-S.,Montpellier University |
Escote X.,University Hospital of Tarragona Joan |
Vendrell J.,University Hospital of Tarragona Joan |
And 2 more authors.
Endocrinology | Year: 2010
Cell cycle regulators such as cyclins, cyclin-dependent kinases, or retinoblastoma protein play important roles in the differentiation of adipocytes. In the present paper, we investigated the role of cyclin G2 as a positive regulator of adipogenesis. Cyclin G2 is an unconventional cyclin which expression is upregulated during growth inhibition or apoptosis. Using the 3T3-F442A cell line, we observed an upregulation of cyclin G2 expression at protein and mRNA levels throughout the process of cell differentiation, with a further induction of adipogenesis when the protein is transiently overexpressed. We show here that the positive regulatory effects of cyclin G2 in adipocyte differentiation are mediated by direct binding of cyclin G2 to peroxisome proliferator-activated receptor γ (PPARγ), the key regulator of adipocyte differentiation. The role of cyclin G2 as a novel PPARγ coactivator was further demonstrated by chromatin immunoprecipitation assays, which showed that the protein is present in the PPARγ-responsive element of the promoter of aP2, which is a PPARγ target gene. Luciferase reporter gene assays, showed that cyclin G2 positively regulates the transcriptional activity of PPARγ. The role of cyclin G2 in adipogenesis is further underscored by its increased expression in mice fed a high-fat diet. Taken together, our results demonstrate a novel role for cyclin G2 in the regulation of adipogenesis. Copyright © 2010 by The Endocrine Society.
Sirvent J.-M.,University of Franca |
Ferri C.,University Hospital of Tarragona Joan |
Baro A.,University of Franca |
Murcia C.,University of Franca |
Lorencio C.,University of Franca
American Journal of Emergency Medicine | Year: 2015
Abstract Objective The objective was to assess whether fluid balance had a determinant impact on mortality rate in a cohort of critically ill patients with severe sepsis or septic shock. Design A prospective and observational study was carried out on an inception cohort. Setting The setting was an intensive care unit of a university hospital. Patients Patients admitted consecutively in the intensive care unit who were diagnosed with severe sepsis or septic shock were included. Interventions Demographic, laboratory, and clinical data were registered, as well as time of septic shock onset, illness severity (Simplified Acute Physiology Score II, Sepsis-related Organ Failure Assessment), and comorbidities. Daily and accumulated fluid balance was registered at 24, 48, 72, and 96 hours. Survival curves representing 28-day mortality were built according to the Kaplan-Meier method. Results A total of 42 patients were included in the analysis: men, 64.3%; mean age, 61.8 ± 15.9 years. Septic shock was predominant in 69% of the cases. Positive blood cultures were obtained in 17 patients (40.5%). No age, sex, Sepsis-related Organ Failure Assessment, creatinine, lactate, venous saturation of O2, and troponin differences were observed upon admission between survivors and nonsurvivors. However, higher Simplified Acute Physiology Score II was observed in nonsurvivors, P =.016. Nonsurvivors also showed higher accumulated positive fluid balance at 48, 72, and 96 hours with statistically significant differences. Besides, significant differences (P =.02) were observed in the survival curve with the risk of mortality at 72 hours between patients with greater than 2.5 L and less than 2.5 L of accumulated fluid balance. Conclusions Fluid administration at the onset of severe sepsis or septic shock is the first line of hemodynamic treatment. However, the accumulated positive fluid balance in the first 48, 72, and 96 hours is associated with higher mortality in these critically ill patients. © 2014 Elsevier Inc. All rights reserved.