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Nasarre L.,Hospital Of La Santa Creu I Sant Pau | Juan-Babot O.,Hospital Of La Santa Creu I Sant Pau | Gastelurrutia P.,Fundacio Institute Dinvestigacio En Ciencies Of La Salut Germans Trias I Pujol | Llucia-Valldeperas A.,Fundacio Institute Dinvestigacio En Ciencies Of La Salut Germans Trias I Pujol | And 3 more authors.
Acta Diabetologica | Year: 2014

Lipoprotein receptor expression plays a crucial role in the pathophysiology of adipose tissue in in vivo models of diabetes. However, there are no studies in diabetic patients. The aims of this study were to analyze (a) low-density lipoprotein receptor-related protein 1 (LRP1) and very low-density lipoprotein receptor (VLDLR) expression in epicardial and subcutaneous fat from type 2 diabetes mellitus compared with nondiabetic patients and (b) the possible correlation between the expression of these receptors and plasmatic parameters. Adipose tissue biopsy samples were obtained from diabetic (n = 54) and nondiabetic patients (n = 22) undergoing cardiac surgery before the initiation of cardiopulmonary bypass. Adipose LRP1 and VLDLR expression was analyzed at mRNA level by real-time PCR and at protein level by Western blot analysis. Adipose samples were also subjected to lipid extraction, and fat cholesterol ester, triglyceride, and free cholesterol contents were analyzed by thin-layer chromatography. LRP1 expression was higher in epicardial fat from diabetic compared with nondiabetic patients (mRNA 17.63 ± 11.37 versus 7.01 ± 4.86; P = 0.02; protein 11.23 ± 7.23 versus 6.75 ± 5.02, P = 0.04). VLDLR expression was also higher in epicardial fat from diabetic patients but only at mRNA level (231.25 ± 207.57 versus 56.64 ± 45.64, P = 0.02). No differences were found in the expression of LRP1 or VLDLR in the subcutaneous fat from diabetic compared with nondiabetic patients. Epicardial LRP1 and VLDLR mRNA overexpression positively correlated with plasma triglyceride levels (R 2 = 0.50, P = 0.01 and R 2 = 0.44, P = 0.03, respectively) and epicardial LRP1 also correlated with plasma glucose levels (R 2 = 0.33, P = 0.03). These results suggest that epicardial overexpression of certain lipoprotein receptors such as LRP1 and VLDLR expression may play a key role in the alterations of lipid metabolism associated with type 2 diabetes mellitus. © 2012 Springer-Verlag Italia.


Cardona P.-J.,Fundacio Institute Dinvestigacio En Ciencies Of La Salut Germans Trias I Pujol | Cardona P.-J.,Autonomous University of Barcelona | Vilaplana C.,Fundacio Institute Dinvestigacio En Ciencies Of La Salut Germans Trias I Pujol | Vilaplana C.,Autonomous University of Barcelona
PLoS ONE | Year: 2014

Although contacts between tuberculosis patients may result in multiple consecutive infections (MCI), no experimental animal models consider this fact when used in basic studies. Moreover, the current TB vaccine (BCG) has demonstrated a limited protection in humans. In this study we evaluate the effect of tuberculosis MCI by way of a simple mathematical analysis using data from the low dose aerosol murine experimental model. The results show that a higher number of, or shorter intervals between, multiple consecutive infections reduce the protective effect of BCG. This is due to both the increase in bacillary load at the stationary level of the infection, and the protective immune response induced by the infection itself. This factor must therefore be taken into account when designing new prophylactic strategies as candidate vaccines for the replacement of BCG. © 2014 Cardona, Vilaplana.


Revuelta-Lopez E.,Hospital Of La Santa Creu I Sant Pau | Castellano J.,Hospital Of La Santa Creu I Sant Pau | Roura S.,Fundacio Institute Dinvestigacio En Ciencies Of La Salut Germans Trias I Pujol | Galvez-Monton C.,Fundacio Institute Dinvestigacio En Ciencies Of La Salut Germans Trias I Pujol | And 4 more authors.
Arteriosclerosis, Thrombosis, and Vascular Biology | Year: 2013

OBJECTIVE - : Hypoxia disturbs vascular function by promoting extracellular matrix remodeling. Extracellular matrix integrity and composition are modulated by metalloproteinases (MMPs). Our aim was to investigate the role of low-density lipoprotein receptor-related protein 1 (LRP1) in regulating MMP-9/MMP-2 activation and vascular smooth muscle cells (VSMCs) migration in response to hypoxia, and to elucidate the LRP1-signaling pathways involved in this process. APPROACH AND RESULTS - : Western blot analysis showed that hypoxia induced a sustained phosphorylation of proline-rich tyrosine kinase 2 concomitantly with LRP1 overexpression in human VSMCs (hVSMCs). Deletion of LRP1 using small-interfering RNA technology or treatment of hVSMCs with the Src family kinase inhibitor PP2 impaired hypoxia-induced phosphorylation of proline-rich tyrosine kinase 2 levels. Coimmunoprecipitation experiments showed that the higher amounts of phosphorylation of proline-rich tyrosine kinase 2/LRP1β immunoprecipitates in hypoxic hVSMCs were abolished in PP2-treated hVSMCs. Both LRP1 silencing and PP2 treatment were highly effective in the prevention of hypoxia-induced MMP-9 activation and hVSMC migration. Cellular subfractionation experiments revealed that PP2 effects may be caused by impairment of hypoxia-induced nuclear factor-κβ translocation to the nucleus. ELISA measurements showed that LRP1 silencing but not PP2 treatment increased interleukin-1β, interleukin-6, and monocyte chemoattractant protein-1 secretion by hypoxic hVSMCs. CONCLUSIONS - : Our findings determine a crucial role of LRP1-mediated Pyk2 phosphorylation on hypoxia-induced MMP-9 activation and hVSMC migration and therefore in hypoxia-induced vascular remodeling. Both LRP1 silencing and PP2 treatments also influence hypoxia-induced proinflammatory effects in hVSMCs. Therefore, further studies are required to establish therapeutical strategies that efficiently modulate vascular remodeling and inflammation associated with hypoxia-vascular diseases. © 2013 American Heart Association, Inc.


Mundet L.,Autonomous University of Barcelona | Mundet L.,Fundacio Institute Dinvestigacio En Ciencies Of La Salut Germans Trias I Pujol | Ribas Y.,Consorci Sanitari de Terrassa | Arco S.,Badalona Serveis Assistencials | And 3 more authors.
Journal of Neurogastroenterology and Motility | Year: 2016

Background/Aims To explore and compare quality of life (QoL) differences in female and male patients with fecal incontinence. Methods Ninety-one patients with fecal incontinence (60 women, mean (SD) age 64.13 (9.72) years; 31 men, mean (SD) age 63.61 (13.33) years) were assessed for pathophysiology (anorectal manometry and ultrasound), clinical severity (Wexner and Vaizey scales), QoL (Fecal Incontinence Quality of Life Score [FIQL]) and health status (EQ-5D). Results External and internal anal sphincter impairment rates were 96.5% and 70.2%, respectively, in women, compared to 30% and 43.3% respectively in men (P < 0.05). Clinical severity was similar in both sexes, with mean (SD) Wexner scores of 10.95 (4.35) for women and 9.81 (4.30) for men, and mean (SD) Vaizey scores of 13.27 (4.66) for women and 11.90 (5.22) for men. Scores for women were significantly lower for all FIQL depression and coping subscales (P < 0.001) and the EQ-5D depression subscale (P < 0.01). EQ-5D index was 0.687 (0.20) for women and 0.835 (0.15) for men (P < 0.001). QoL was negatively affected by female gender (-1.336), anxiety/depression (-1.324) and clinical severity (-0.302), whereas age had a positive impact (0.055 per year) (P < 0.01). Conclusions The pathophysiology of fecal incontinence differed between the sexes. For similar severity scores, impact on QoL was higher in women. Gender had the highest impact on QoL compared to other factors. QoL measurements should be part of assessment and treatment protocols. © The Korean Society of Neurogastroenterology and Motility.


Bago J.R.,CIBER ISCIII | Alieva M.,CIBER ISCIII | Soler C.,Fundacio Institute Dinvestigacio En Ciencies Of La Salut Germans Trias I Pujol | Rubio N.,CIBER ISCIII | Blanco J.,CIBER ISCIII
Molecular Therapy | Year: 2013

Multipotent human adipose tissue mesenchymal stromal cells (hAMSCs) are promising therapy vehicles with tumor-homing capacity that can be easily modified to deliver cytotoxicity activating systems in the proximity of tumors. In a previous work, we observed that hAMSCs are very effective delivering cytotoxicity to glioma tumors. However, these results were difficult to reconcile with the relatively few hAMSCs surviving implantation. We use a bioluminescence imaging (BLI) platform to analyze the behavior of bioluminescent hAMSCs expressing HSV-tTK in a U87 glioma model and gain insight into the therapeutic mechanisms. Tumor-implanted hAMSCs express the endothelial marker PECAM1(CD31), integrate in tumor vessels and associate with CD133-expressing glioma stem cells (GSC). Inhibition of endothelial lineage differentiation in hAMSCs by Notch1 shRNA had no effect on their tumor homing and growth-promoting capacity but abolished the association of hAMSCs with tumor vessels and CD133 + tumor cells and significantly reduced their tumor-killing capacity. The current strategy allowed the study of tumor/stroma interactions, showed that tumor promotion and tumor-killing capacities of hAMSCs are based on different mechanisms. Our data strongly suggest that the therapeutic effectiveness of hAMSCs results from their association with special tumor vascular structures that also contain GSCs. © The American Society of Gene and Cell Therapy.


PubMed | Karolinska Institutet, World Health Organization, Kilimanjaro Clinical Research Institute, Northwick Park Hospital and 7 more.
Type: | Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America | Year: 2015

Despite concerted efforts over the past 2 decades at developing new diagnostics, drugs, and vaccines with expanding pipelines, tuberculosis remains a global emergency. Several novel diagnostic technologies show promise of better point-of-care rapid tests for tuberculosis including nucleic acid-based amplification tests, imaging, and breath analysis of volatile organic compounds. Advances in new and repurposed drugs for use in multidrug-resistant (MDR) or extensively drug-resistant (XDR) tuberculosis have focused on development of several new drug regimens and their evaluation in clinical trials and now influence World Health Organization guidelines. Since the failure of the MVA85A vaccine 2 years ago, there have been no new tuberculosis vaccine candidates entering clinical testing. The current status quo of the lengthy treatment duration and poor treatment outcomes associated with MDR/XDR tuberculosis and with comorbidity of tuberculosis with human immunodeficiency virus and noncommunicable diseases is unacceptable. New innovations and political and funder commitment for early rapid diagnosis, shortening duration of therapy, improving treatment outcomes, and prevention are urgently required.


Galvez-Monton C.,Fundacio Institute Dinvestigacio En Ciencies Of La Salut Germans Trias I Pujol | Prat-Vidal C.,Fundacio Institute Dinvestigacio En Ciencies Of La Salut Germans Trias I Pujol | Roura S.,Fundacio Institute Dinvestigacio En Ciencies Of La Salut Germans Trias I Pujol | Soler-Botija C.,Fundacio Institute Dinvestigacio En Ciencies Of La Salut Germans Trias I Pujol | And 3 more authors.
Revista Espanola de Cardiologia | Year: 2013

Heart failure is the end-stage of many cardiovascular diseases - such as acute myocardial infarction - and remains one of the most appealing challenges for regenerative medicine because of its high incidence and prevalence. Over the last 20 years, cardiomyoplasty, based on the isolated administration of cells with regenerative capacity, has been the focal point of most studies aimed at regenerating the heart. Although this therapy has proved feasible in the clinical setting, the degree of infarcted myocardium regenerated and of improved cardiac function are at best modest. Hence, tissue engineering has emerged as a novel technology using cells with regenerative capacity, biological and/or synthetic materials, growth, proangiogenic and differentiation factors, and online registry systems, to induce the regeneration of whole organs or locally damaged tissue. The next step, seen recently in pioneering animal studies, is de novo generation of bioartificial hearts by decellularization and preservation of supporting structures for their subsequent repopulation with new contractile, vascular muscle tissue. Ultimately, this new approach would entail transplantation of the «rebuilt» heart, reestablishing cardiac function in the recipient. © 2012 Sociedad Española de Cardiología. Publicado por Elsevier España, S.L. Todos los derechos reservados.


Kumru H.,Institute Universitari Of Neurorehabilitacio Adscrit Uab | Kumru H.,University of Barcelona | Kumru H.,Fundacio Institute Dinvestigacio En Ciencies Of La Salut Germans Trias I Pujol | Portell E.,Institute Universitari Of Neurorehabilitacio Adscrit Uab | And 6 more authors.
Parkinsonism and Related Disorders | Year: 2014

Background: No studies have examined the association between RLS and the sequelae of poliomyelitis (PM). We studied the frequency and severity of RLS in a group of consecutive patients with the sequelae of poliomyelitis (PM) and the effect of treatment with dopaminergic drugs. Methods: A diagnosis of RLS was made according to the criteria of the International RLS Study Group, and severity was assessed by the RLS rating scale. Information on sex, age, age at onset, site affected by PM, disease duration of PM, and history of post-polio syndrome (pPS) was obtained in a cohort of 52 PM patients. Result: The mean age was 55.9±6.5 years; 39 patients had post-polio syndrome (75%). RLS was diagnosed in 21 (40.4%) patients. Sixteen of the 21 patients (76.2%) with RLS had pPS, which was similar to the non-RLS group (74.2% patients with pPS). RLS symptoms were very severe in 5 patients, severe in 13, moderate in 2 and mild in 1. Nineteen of the 21 patients with RLS had symptoms predominantly in the more affected lower limb (90% of patients). Sixteen patients received dopaminergic agonist treatment with a significant reduction in their scores on the RLS severity scale from 28.3±4.7 to 6.9±7.3 (. p<0.001). Discussion: RLS occurs frequently in patients with PM, both in those with and without pPS, and responds well to treatment with dopaminergic drugs. © 2014 Elsevier Ltd.


Terre R.,Neurorehabilitation Hospital | Terre R.,Institute Universitari Of Neurorehabilitacio | Terre R.,Autonomous University of Barcelona | Terre R.,Fundacio Institute Dinvestigacio En Ciencies Of La Salut Germans Trias I Pujol | And 4 more authors.
European Journal of Neurology | Year: 2015

Background and purpose: To evaluate the effectiveness of neuromuscular electrical stimulation (NMES) treatment in patients with oropharyngeal dysphagia secondary to acquired brain injury. Methods: Twenty patients with neurological oropharyngeal dysphagia (14 stroke and six severe traumatic brain injury) were enrolled in a prospective randomized study, with patients and assessors blinded (to group allocation): 10 patients underwent NMES and conventional swallowing therapy and 10 patients underwent sham electrical stimulation (SES) and conventional swallowing therapy. Both groups completed 20 sessions. At baseline, at the end of treatment (1 month) and at 3-month follow-up, clinical, videofluoroscopic and esophageal manometric analyses were done. Feeding swallowing capacity was evaluated using the functional oral intake scale (FOIS). Results: Mean FOIS score before treatment was 1.9 for the NMES group and 2.1 for the SES group. After treatment, the NMES group increased by 2.6 points (4.5 points) compared with only 1 point (3.1 points) for the SES group (P = 0.005). At 3 months of follow-up, mean scores were 5.3 and 4.6 respectively; thus, both groups improved similarly. At that time point (3 months), tracheal aspiration persisted in six patients in each group. However, a significant improvement in relation to the bolus viscosity at which aspiration appeared was found in the NMES group versus the SES group (P = 0.015). Also, a significant increase (P = 0.04) in pharyngeal amplitude contraction was observed at the end of treatment (1 month) in the NMES group compared with the SES group. Conclusion: Neuromuscular electrical stimulation significantly accelerated swallowing function improvement in patients with oropharyngeal dysphagia secondary to acquired brain injury. © 2015 EAN.


Vilaplana C.,Fundacio Institute Dinvestigacio En Ciencies Of La Salut Germans Trias I Pujol | Marzo E.,Fundacio Institute Dinvestigacio En Ciencies Of La Salut Germans Trias I Pujol | Tapia G.,Autonomous University of Barcelona | Diaz J.,Fundacio Institute Dinvestigacio En Ciencies Of La Salut Germans Trias I Pujol | And 2 more authors.
Journal of Infectious Diseases | Year: 2013

C3HeB/FeJ mice infected with Mycobacterium tuberculosis were used in an experimental animal model mimicking active tuberculosis in humans to evaluate the effect of antiinflammatory agents. No other treatment but ibuprofen was given, and it was administered when the animals' health started to deteriorate. Animals treated with ibuprofen had statistically significant decreases in the size and number of lung lesions, decreases in the bacillary load, and improvements in survival, compared with findings for untreated animals. Because antiinflammatory agents are already on the market, further clinical trials should be done to evaluate this effect in humans as soon as possible, to determine their suitability as coadjuvant tuberculosis treatment. © 2013 The Author 2013. All rights reserved.

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