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Rios M.,University of Santiago de Compostela | Foretz M.,University of Paris Descartes | Viollet B.,University of Paris Descartes | Prieto A.,Complejo Hospitalario Universitario Of Santiago Of Compostela | And 3 more authors.
Cancer Research | Year: 2013

50-AMP-activated protein kinase (AMPK) is an energy sensor that controls cell metabolism, and it has been related to apoptosis and cell-cycle arrest. Although its role in metabolic homeostasis is well documented, its function in cancer is much less clear. In this study, we examined the role of AMPK in a mouse model of astrocytoma driven by oncogenic H-RasV12 and/or with PTEN deletion based on the common constitutive activation of the Raf/MEK/ERK and PI3K/AKT cascades in human astrocytomas. We also evaluated the activity and role of AMPK in human glioblastoma cells and xenografts. AMPK was constitutively activated in astrocytes expressing oncogenic H-RasV12 in parallel with high cell division rates. Genetic deletion of AMPK or attenuation of its activity in these cells was sufficient to reduce cell proliferation. The levels of pAMK were always related to the levels of phosphorylated retinoblastoma (Rb) at Ser804, which may indicate an AMPKmediated phosphorylation of Rb. We confirmed this AMPK-Rb relationship in human glioblastoma cell lines and xenografts. In clinical specimens of human glioblastoma, elevated levels of activated AMPK appeared especially in areas of high proliferation surrounding the blood vessels. Together, our findings indicate that the initiation and progression of astrocytic tumors relies upon AMPK-dependent control of the cell cycle, thereby identifying AMPK as a candidate therapeutic target in this setting. © 2013 American Association for Cancer Research.

Olmos M.A.M.,Complejo Hospitalario Universitario Of Santiago Of Compostela
Nutricion Hospitalaria | Year: 2015

Telemedicine represents the union of information technology and telecommunication services in health. This allows the improvement of health care, especially in underserved areas, bringing professionals working in continuing education and improving patient care at home. The application of telemedicine in various hospital complexes, clinics and health centers, has helped to provide a better service, within the parameters of efficiency, effectiveness, cost-benefit, with increasing satisfaction of medical staff and patients. The development and application of various types of telemedicine, the technological development of audio, text, video and data, and constant improvement of infrastructure in telecommunications, have favored the expansion and development of telemedicine in various medical specialties. The use of electronic health records by different health professionals can have a positive impact on the care provided to patients. This should also be supported by the development of better health policies, legal security and greater awareness in health professionals and patients regarding the potential benefits. Regarding the clinical activity in Nutrition, new technologies also provide an opportunity to improve in various educational, preventive, diagnostic and treatment aspects, including shared track between Nutrition Units and Primary Care Teams, for patients who need home nutritional care at, with shared protocols, providing teleconsultation in required cases and avoiding unnecessary travel to hospital. © 2015, Grupo Aula Medica S.A. All rights reserved.

Alvarez E.,University of Santiago de Compostela | Rodino-Janeiro B.K.,University of Santiago de Compostela | Ucieda-Somoza R.,Complejo Hospitalario Universitario Of Santiago Of Compostela | Gonzalez-Juanatey J.R.,University of Santiago de Compostela
Journal of Cardiovascular Pharmacology | Year: 2010

Endothelial dysfunction has been linked to reactive oxygen species (ROS) production by nicotinamide adenine dinucleotide phosphate reduced (NADPH) oxidase. Angiotensin II (ANG), which levels are elevated in some cardiovascular diseases, can stimulate this enzyme, whereas statins have been demonstrated pleiotropic effects related with the restoration of endothelial function. Therefore, our purpose was to study the mechanism of the possible beneficial effects of pravastatin on ANG-activated human umbilical vein endothelial cells (HUVEC). ANG induced an increase in the extracellular superoxide anion produced by NADPH oxidase but had no effect in the intracellular ROS production. Pravastatin, which alone did not have any effect on ROS production, totally blocked the stimulating effects of ANG when combined with it. These effects were not due to a direct action of ANG or pravastatin on the activity of NADPH oxidase measured in HUVEC lisates. On the contrary, the results correlated well with other effects of ANG: a Nox4 and p22phox upregulated expression and an enhanced Nox4 translocation to the cell membrane. All these effects were inhibited by pravastatin, which had no effect when incubated alone. These data reveal for the first time that pravastatin interrupts the signaling pathway activated by ANG that leads to an enhanced NADPH oxidase activity at the cell membrane of HUVEC. For that, pravastatin inhibits ANG-induced upregulation of catalytic NADPH oxidase subunits and blocks the migration of them to the endothelial cell membrane. © 2010 by Lippincott Williams & Wilkins.

Romero-Gomez M.,University of Seville | Berenguer M.,University of Valencia | Molina E.,Complejo Hospitalario Universitario Of Santiago Of Compostela | Calleja J.L.,Autonomous University of Madrid
Journal of Hepatology | Year: 2013

The addition of protease inhibitors, boceprevir or telaprevir, to peginterferon + ribavirin (PegIFN/RBV) increases the frequency as well as the severity, and hence, clinical relevance of anemia, which has now become one of the major complications associated with triple therapy. Most significant factors associated with anemia in patients receiving triple therapy include older age, lower body mass index (BMI), advanced fibrosis, and lower baseline hemoglobin. The variability in inosine triphosphate pyrophosphatase (ITPA) gene, which encodes a protein that hydrolyses inosine triphosphate (ITP), has been identified as an essential genetic factor for anemia both in dual and triple therapy. The correct management of anemia is based on anticipation, characterization and therapeutic management. Basically, anemia can be characterized in 3 types: ferropenic (mostly in fertile women), thalassemic type hemolytic anemia, and anemia from chronic processes. Functional deficit of iron should also be excluded in patients with normal ferritin and lower saturation of transferrin. Ribavirin dose reduction and epoetin, sequentially, are indicated in the management of anemia. Epoetin non-response can be caused by lack of time, type of anemia, functional iron deficit or erythropoietin resistance. In the transplantation setting, adding a protease inhibitor to PegIFN/RBV results in a significant increase in the incidence and severity of anemia and, as a consequence, a greater need for epoetin, transfusions, and ribavirin dose reductions. Packed red cell transfusions are utilized when hemoglobin decreases to less than 7.5 g/dl and/or there are clinical symptoms and/or there is no response to other therapeutic measures. © 2013 European Association for the Study of the Liver. Published.

Andujar-Plata P.,Complejo Hospitalario Universitario Of Santiago Of Compostela | Pi-Sunyer X.,Roosevelt University | Laferrere B.,Roosevelt University
Diabetes Research and Clinical Practice | Year: 2012

Metformin is a cornerstone in the treatment of type 2 diabetes. Although its mechanism of action is not well understood, there is new evidence about its possible role in cancer. A Pubmed search from 1990 to 2011 was done using the terms metformin, cancer, mechanism of action, diabetes treatment and prevention. We found more than one thousand articles and reviewed studies that had assessed the efficacy of metformin in treatment and prevention of type 2 diabetes and its mechanisms of actions, as well as articles on its antitumoral effects. We found that the United Kingdom Prospective Diabetes Study and the Diabetes Prevention Program have demonstrated the efficacy of metformin in terms of treatment and prevention of type 2 diabetes; metformin is safe, cost effective and remains the first line of diabetes therapy with diet and exercise. The mechanisms of action include a decrease of hepatic insulin resistance, change in bile acids metabolism, incretins release and decreased amyloid deposits. The AMP-activated protein kinase seems to be an important target for these effects. Epidemiological retrospective studies point out a possible association between metformin and decreased cancer risk, data supported by in vitro and animal studies. These data should trigger randomized controlled trials to prove or disprove this additional benefit of metformin. © 2011 Elsevier Ireland Ltd.

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