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Damman P.,University of Amsterdam | Iniguez A.,Hospital Universitario Of Vigo | Klomp M.,University of Amsterdam | Beijk M.,University of Amsterdam | And 8 more authors.
Circulation Journal | Year: 2011

Background: We evaluated the Genous™ Bio-engineered R stent™ in elderly patients undergoing non-urgent percutaneous coronary intervention. The elderly have an increased risk of (temporary) discontinuation of clopidogrel, which is associated with a higher risk of developing stent thrombosis (ST). Methods and Results: In the e-HEALING registry, 2,651 patients were <65, 1,403 were 65-74 and 869 were =75 years old. The 12-month primary outcome was target vessel failure (TVF), defined as target vessel-related cardiac death or myocardial infarction and target vessel revascularization. Secondary outcomes included target lesion revascularization (TLR) and ST. Cumulative event rates were estimated with the Kaplan-Meier method and compared with a log-rank test. TVF occurred significantly more often in elderly patients compared with younger patients (7.0% in patients aged <65, 8.8% in patients aged 65-74 and 11.7% in patients aged =75 years, P<0.001). There was a trend to higher TLR with increasing age (log-rank P=0.06) and no difference in ST. Conclusions: The 1-year results of the Genous stent in a population of elderly patients show a significantly higher TVF rate compared with younger patients, mainly driven by a higher mortality. Although there was a trend to higher TLR rates with increasing age, there was no difference in ST. This attests to the safety of this therapy for the elderly, in whom there could be concerns with administering long-term dual antiplatelet therapy.

Santacatterina F.,Autonomous University of Madrid | Santacatterina F.,Research Center Biomedica En Red Of Enfermedades Raras Ciberer | Santacatterina F.,Institute Investigacion Hospital 12 Of Octubre | Chamorro M.,Autonomous University of Madrid | And 15 more authors.
Journal of Translational Medicine | Year: 2015

Background: Muscle diseases have been associated with changes in the expression of proteins involved in energy metabolism. To this aim we have developed a number of monoclonal antibodies against proteins of energy metabolism. Methods: Herein, we have used Reverse Phase Protein Microarrays (RPMA), a high throughput technique, to investigate quantitative changes in protein expression with the aim of identifying potential biomarkers in rare neuromuscular diseases. A cohort of 73 muscle biopsies that included samples from patients diagnosed of Duchenne (DMD), Becker (BMD), symptomatic forms of DMD and BMD in female carriers (Xp21 Carriers), Limb Girdle Muscular Dystrophy Type 2C (LGMD2C), neuronal ceroid lipofuscinosis (NCL), glycogenosis type V (Mc Ardle disease), isolated mitochondrial complex I deficiency, intensive care unit myopathy and control donors were investigated. The nineteen proteins of energy metabolism studied included members of the mitochondrial oxidation of pyruvate, the tricarboxylic acid cycle, β-oxidation of fatty acids, electron transport and oxidative phosphorylation, glycogen metabolism, glycolysis and oxidative stress using highly specific antibodies. Results: The results indicate that the phenotype of energy metabolism offers potential biomarkers that could be implemented to refine the understanding of the biological principles of rare diseases and, eventually, the management of these patients. Conclusions: We suggest that some biomarkers of energy metabolism could be translated into the clinics to contribute to the improvement of the clinical handling of patients affected by rare diseases. © 2015 Santacatterina et al.

The utility of self-monitoring of blood glucose (SMBG) in patients with type 1 diabetes and in those with type 2 diabetes treated with insulin is well accepted, however, consensus on whether people with type 2 diabetes who are not taking insulin should monitor their blood glucose levels has not been reached. The aim of the present review was to analyze data available on SMGB in type 2 diabetic patients and subsequently elaborate recommendations for its use. Nine clinical trials and 5 systematic reviews were consulted. Furthermore, guides from scientific societies were also consulted. I can conclude, under my personal point of view that SMBG must be introducing as part of a structured education programme for those newly diagnosed with type 2 diabetes even in those only treated with life-style modifications provides people with the opportunity to learn about the impact that food and physical activity have on their glycaemia control. These patients should monitor their blood glucose pre- and post-prandial at least once per month. The frequency should increase when values of glycosilate haemoglobin are out of the objectives. © 2009 Elsevier España, S.L. All rights reserved.

Sanchez-Arago M.,Autonomous University of Madrid | Formentini L.,Autonomous University of Madrid | Martinez-Reyes I.,Autonomous University of Madrid | Garcia-Bermudez J.,Autonomous University of Madrid | And 11 more authors.
Oncogenesis | Year: 2013

Recent findings in colon cancer cells indicate that inhibition of the mitochondrial H+-adenosine triphosphate (ATP) synthase by the ATPase inhibitory factor 1 (IF1) promotes aerobic glycolysis and a reactive oxygen species (ROS)-mediated signal that enhances proliferation and cell survival. Herein, we have studied the expression, biological relevance, mechanism of regulation and potential clinical impact of IF1 in some prevalent human carcinomas. We show that IF1 is highly overexpressed in most (>90%) of the colon (n=64), lung (n=30), breast (n=129) and ovarian (n=10) carcinomas studied as assessed by different approaches in independent cohorts of cancer patients. The expression of IF1 in the corresponding normal tissues is negligible. By contrast, the endometrium, stomach and kidney show high expression of IF1 in the normal tissue revealing subtle differences by carcinogenesis. The overexpression of IF1 also promotes the activation of aerobic glycolysis and a concurrent ROS signal in mitochondria of the lung, breast and ovarian cancer cells mimicking the activity of oligomycin. IF1-mediated ROS signaling activates cell-type specific adaptive responses aimed at preventing death in these cell lines. Remarkably, regulation of IF1 expression in the colon, lung, breast and ovarian carcinomas is exerted at post-transcriptional levels. We demonstrate that IF1 is a short-lived protein (t1/2 ~ 100 min) strongly implicating translation and/or protein stabilization as main drivers of metabolic reprogramming and cell survival in these human cancers. Analysis of tumor expression of IF1 in cohorts of breast and colon cancer patients revealed its relevance as a predictive marker for clinical outcome, emphasizing the high potential of IF1 as therapeutic target. © 2013 Macmillan Publishers Limited.

Aldea M.,Research Center Biomedica En Red Of Enfermedades Raras Ciberer | Aldea M.,Autonomous University of Madrid | Clofent J.,Hospital Universitario Of Vigo | Nunez de Arenas C.,Research Center Biomedica En Red Of Enfermedades Raras Ciberer | And 6 more authors.
Cancer Letters | Year: 2011

A reverse phase protein microarray approach has been applied to quantify proteins of energy metabolism in normal and tumor biopsies of colorectal cancer (CRC) patients. The metabolic proteome of CRC specimens revealed a profound shift towards and enhanced glycolytic phenotype and concurrent mitochondrial alteration. The metabolic signature discriminated CRC patients with highly significant differences in overall and disease-free prognosis. The quantification of the bioenergetic signature of the tumor offers a relevant biomarker of CRC that could contribute in the handling of these patients. © 2011 Elsevier Ireland Ltd.

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