Dominguez-Rodriguez A.,Hospital Universitario Of Canarias |
Abreu-Gonzalez P.,University of La Laguna |
Avanzas P.,Hospital Central de Asturias
Frontiers in Bioscience | Year: 2012
Melatonin, a circadian hormone with marked antioxidant properties, has been shown to protect against ischemia-reperfusion myocardial damage, especially when administered during reperfusion period. Melatonin has cardioprotective properties via its direct free radical scavenging and its indirect antioxidant activity. Melatonin efficiently interacts with various reactive oxygen and reactive nitrogen species and it also upregulates antioxidant enzymes and downregulates pro-oxidant enzymes. In addition, melatonin demonstrated blood pressure lowering, lipid profile normalizing and anti-inflammatory properties. The lack of these cardioprotective effects due to insufficient melatonin levels might be associated with several cardiovascular pathologies including ischemic heart disease. Patients with acute coronary syndrome or after myocardial infarction were shown to have reduced nighttime melatonin levels and 6-sulfatoxymelatonin urinary excretion. These alterations might translate to increased cardiovascular risk observed in acute myocardial infarction patients with low melatonin levels; and a mutation in melatonin receptors might augment the risk for acute myocardial infarction. Therefore, it is expected that melatonin administration could play a clinically relevant role in the pharmacotherapy of ischemic heart disease; an assumption supported by low toxicity and high safety of melatonin.
Safety and effectiveness of two treatment regimes with tranexamic acid to minimize inflammatory response in elective cardiopulmonary bypass patients: a randomized double-blind, dose-dependent, phase IV clinical trial.
Jimenez J.J.,Hospital Universitario Of Canarias
Journal of cardiothoracic surgery | Year: 2011
In cardiopulmonary bypass (CPB) patients, fibrinolysis may enhance postoperative inflammatory response. We aimed to determine whether an additional postoperative dose of antifibrinolytic tranexamic acid (TA) reduced CPB-mediated inflammatory response (IR). We performed a randomized, double-blind, dose-dependent, parallel-groups study of elective CPB patients receiving TA. Patients were randomly assigned to either the single-dose group (40 mg/Kg TA before CPB and placebo after CPB) or the double-dose group (40 mg/Kg TA before and after CPB). 160 patients were included, 80 in each group. The incident rate of IR was significantly lower in the double-dose-group TA2 (7.5% vs. 18.8% in the single-dose group TA1; P = 0.030). After adjusting for hypertension, total protamine dose and temperature after CPB, TA2 showed a lower risk of IR compared with TA1 [OR: 0.29 (95% CI: 0.10-0.83), (P = 0.013)]. Relative risk for IR was 2.5 for TA1 (95% CI: 1.02 to 6.12). The double-dose group had significantly lower chest tube bleeding at 24 hours [671 (95% CI 549-793 vs. 826 (95% CI 704-949) mL; P = 0.01 corrected-P significant] and lower D-dimer levels at 24 hours [489 (95% CI 437-540) vs. 621(95% CI: 563-679) ng/mL; P = 0.01 corrected-P significant]. TA2 required lower levels of norepinephrine at 24 h [0.06 (95% CI: 0.03-0.09) vs. 0.20(95 CI: 0.05-0.35) after adjusting for dobutamine [F = 6.6; P = 0.014 corrected-P significant]. We found a significant direct relationship between IL-6 and temperature (rho = 0.26; P < 0.01), D-dimer (rho = 0.24; P < 0.01), norepinephrine (rho = 0.33; P < 0.01), troponin I (rho = 0.37; P < 0.01), Creatine-Kinase (rho = 0.37; P < 0.01), Creatine Kinase-MB (rho = 0.33; P < 0.01) and lactic acid (rho = 0.46; P < 0.01) at ICU arrival. Two patients (1.3%) had seizure, 3 patients (1.9%) had stroke, 14 (8.8%) had acute kidney failure, 7 (4.4%) needed dialysis, 3 (1.9%) suffered myocardial infarction and 9 (5.6%) patients died. We found no significant differences between groups regarding these events. Prolonged inhibition of fibrinolysis, using an additional postoperative dose of tranexamic acid reduces inflammatory response and postoperative bleeding (but not transfusion requirements) in CPB patients. A question which remains unanswered is whether the dose used was ideal in terms of safety, but not in terms of effectiveness.
Lorente L.,Hospital Universitario Of Canarias |
Blot S.,Ghent University |
Rello J.,Institute Of Recerca Vall Dhebron
American Journal of Respiratory and Critical Care Medicine | Year: 2010
In the past 2 years, American, Canadian, and European scientific societies have published their new evidence-based guidelines for ventilator-associated pneumonia (VAP) prevention. However, these guidelines did not review some potentially useful strategies, such as the use of an endotracheal tube with an ultrathin cuff membrane, an endotracheal tube with a low-volume/low-pressure cuff, a device for continuous monitoring of the endotracheal tube cuff pressure, a device to remove biofilm from the inner site of the endotracheal tube, and saline instillation before tracheal suctioning. Only a few guidelines analyze the time of tracheostomy, and so no firm recommendations can be made regarding its importance. In addition, the guidelines diverge on the use of heat and moisture exchangers or heated humidifiers and on the use of an endotracheal tube coated with antimicrobial agents. The current review focuses on measures of VAP prevention for which there is no clear recommendation, or the use of which is controversial. A review of the literature suggests that the use of an endotracheal tube with an ultrathin and tapered-shape cuffmembrane and coated in antimicrobial agents may reduce the risk of VAP. These features offer an attractive way to optimize the VAP prevention capacity of endotracheal tubeswitha lumenfor subglottic secretion drainage. We believe that early tracheostomy should be considered, based on the length reduction of mechanical ventilation and intensive care unit stay, reduction of mortality, and on patient comfort, although early tracheostomy has not yet been shown to favorably impact the incidence of VAP. We believed that heat and moisture exchangers should be considered based on the benefits in terms of cost savings. More research is necessary to clarify the role of continuous cuff pressure monitoring, removal of biofilm formation in the endotracheal tubes, and routine saline instillation before tracheal suctioning.
Nicolas-Perez D.,Hospital Universitario Of Canarias
Gastroenterologia y Hepatologia | Year: 2012
Endoscopic submucosal dissection (ESD) can be applied to early gastrointestinal cancers. This technique was developed to achieve radical curative resection and to reduce unnecessary surgical interventions. ESD was designed in eastern countries and is not widely used in the West.Although ESD represents a major therapeutic advance in endoscopy and is performed with curative intent, the complication rate (hemorrhage, perforation) is higher than reported in other techniques, requiring from endoscopists the acquirement of technical skill and experience through a structured and progressive training program to reduce the morbidity associated with this technique and increase its potential benefits. Although there is substantial published evidence on the applications and results of ESD, there are few publications on training in this technique and a standardized training program is lacking. The current article aims to describe the various proposals for training, as well as the basic principles of the technique, its indications, and the results obtained, since theoretical knowledge that would guide endoscopists during the clinical application of ESD is advisable before training begins. Training in an endoscopic technique has a little value without knowledge of the technique's aims, the situations in which it should be applied, and the results that can be expected. © 2011 Elsevier España, S.L. and AEEH y AEG.
Cabrera E.,Hospital Universitario Of Canarias
Oncogene | Year: 2016
Stresses such as hypoxia, nutrient deprivation and acidification disturb protein folding in the endoplasmic reticulum (ER) and activate the Unfolded Protein Response (UPR) to trigger adaptive responses through the effectors, PERK, IRE1 and ATF6. Most of these responses relate to ER homoeostasis; however, here we show that the PERK branch of the UPR also controls DNA replication. Treatment of cells with the non-genotoxic UPR agonist thapsigargin led to a rapid inhibition of DNA synthesis that was attributable to a combination of DNA replication fork slowing and reduced replication origin firing. DNA synthesis inhibition was dependent on the UPR effector PERK and was associated with phosphorylation of the checkpoint adaptor protein Claspin and activation of the Chk1 effector kinase, both of which occurred in the absence of detectable DNA damage. Remarkably, thapsigargin did not inhibit bulk DNA synthesis or activate Chk1 in cells depleted of Claspin, or when Chk1 was depleted or subject to chemical inhibition. In each case thapsigargin-resistant DNA synthesis was due to an increase in replication origin firing that compensated for reduced fork progression. Taken together, our results unveil a new aspect of PERK function and previously unknown roles for Claspin and Chk1 as negative regulators of DNA replication in the absence of genotoxic stress. Because tumour cells proliferate in suboptimal environments, and frequently show evidence of UPR activation, this pathway could modulate the response to DNA replication-targeted chemotherapies.Oncogene advance online publication, 4 July 2016; doi:10.1038/onc.2016.239. © 2016 Macmillan Publishers Limited