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Vilafranca del Penedes, Spain

Granell J.,Camilo Jose Cela University
Journal of Sports Medicine and Physical Fitness | Year: 2014

Aim. The role of zinc and copper has been shown essential in the scope of physical exercise. The outcomes of the studies about changes in the concentrations of these elements in blood, in physical effort situations, are sometimes discordant and seem to be related with the type of the exercise done. The purpose of the study was to determine the changes of zinc and copper in serum and urine produced by two kinds of exercise, designing two tests involving different types of physical exertion, which have been defined as aerobic endurance (AE) and muscular strength (MS). Methods. The study was designed to assess the variations of both elements in two types of exercise; AE, participants: 22 subjects, consisted of run for 40 minutes with a heart rate intensity of ±5 beats per minute from the anaerobic threshold (AnT). MS, participants: 16 subjects, consisted of performing a circuit of 8 different exercises, applying 40% of maximum peak force, until exhaustion. Results. The serum concentration of Zn decreases in both exercises, being statistically significant in the MS (P<0.001). Cu concentration increases significantly in AE (P=0.002) as well as in MS (P<0.001). Urine concentrations of both elements increases after exercise in the two cases (P<0.05 in AE; P<0.001 in MS), the variation of Zn is correlated with proteinuria generated which appears after physical exertion (r=0.59). Conclusion. Findings suggest that changes of Zn and Cu in serum and urine are related to the type of exercise performed, which are higher when there is a big impact on muscular tissues. Source

Cacabelos R.,Camilo Jose Cela University
Neurodegenerative Diseases | Year: 2010

The application of genomic procedures as diagnostic and therapeutic tools is a major challenge for the coming decades. Pharmacogenomic factors may account for 60-90% of drug variability in drug disposition and pharmacodynamics. About 25% of the 100 most prescribed drugs in the USA and the EU are psychotropic drugs, currently used in dementia. Approximately 60-80% of CNS drugs are metabolized via enzymes of the CYP gene superfamily; 18% of neuroleptics are major substrates of CYP1A2 enzymes, 40% of CYP2D6, and 23% of CYP3A4; 24% of antidepressants are major substrates of CYP1A2 enzymes, 5% of CYP2B6, 38% of CYP2C19, 85% of CYP2D6, and 38% of CYP3A4; 7% of benzodiazepines are major substrates of CYP2C19 enzymes, 20% of CYP2D6, and 95% of CYP3A4. About 57.76% of patients with Alzheimer's disease are extensive metabolisers (EMs) for CYP2D6 enzymes, 31.06% are intermediate metabolisers (IMs), 5.28% are poor metabolisers (PMs), and 5.90% are ultrarapid metabolisers (UMs); 73.71% are CYP2C19-EMs, 25.12% IMs, and 1.16% PMs; 60.87% are CYP2C9-EMs, 34.16% IMs, and 4.97% PMs; 82.75% are CYP3A4/5-EMs, 15.88% IMs, and 1.37% UMs. A trigenic cluster integrating CYP2D6+CYP2C19+CYP2C9 polymorphic variants yields 82 different haplotype-like profiles, representing 36 different pharmacogenetic phenotypes in which only 26.51% of patients show a pure 3EM phenotype. These data clearly indicate that the incorporation of pharmacogenomic protocols to dementia research and clinical trials can foster therapeutics optimization by helping to develop cost-effective pharmaceuticals and improve drug efficacy and safety. Copyright © 2010 S. Karger AG, Basel. Source

Cacabelos R.,Camilo Jose Cela University | Cacabelos R.,Institute of Medical Science and Genomic Medicine
Drug Development Research | Year: 2014

Preclinical Research Different epigenetic alterations (DNA methylation, histone modifications, chromatin remodeling, noncoding RNA dysregulation) are associated with the phenotypic expression of complex disorders in which genomic, epigenomic, proteomic, and metabolomic changes, in conjunction with environmental factors, are involved. As epigenetic modifications are reversible and can be potentially targeted by pharmacological and dietary interventions, a series of epigenetic drugs have been developed, including DNA methyltransferase inhibitors (nucleoside analogs, small molecules, bioproducts, antisense oligonucleotides, miRNAs), histone deacetylase inhibitors (short-chain fatty acids, hydroxamic acids, cyclic peptides, benzamides, ketones, sirtuin inhibitors, sirtuin activators), histone acetyltransferase modulators, histone methyltransferase inhibitors, histone demethylase inhibitors, and noncoding RNAs (miRNAs), with potential effects against myelodysplastic syndromes, different types of cancer, and neurodegenerative disorders. Pharmacogenetic and pharmacoepigenetic studies are required for the proper evaluation of efficacy and safety issues in clinical trials with epigenetic drugs. © 2014 Wiley Periodicals, Inc. Source

Cacabelos R.,Camilo Jose Cela University | Cacabelos R.,Institute of Medical Science and Genomic Medicine | Torrellas C.,Institute of Medical Science and Genomic Medicine
Expert Opinion on Drug Discovery | Year: 2014

Introduction: It is assumed that epigenetic modifications are reversible and could potentially be targeted by pharmacological and dietary interventions. Epigenetic drugs are gaining particular interest as potential candidates for the treatment of Alzheimer's disease (AD).Areas covered: This article covers relevant information from over 50 different epigenetic drugs including: DNA methyltransferase inhibitors; histone deacetylase inhibitors; histone acetyltransferase modulators; histone methyltransferase inhibitors; histone demethylase inhibitors; non-coding RNAs (microRNAs) and dietary regimes. The authors also review the pharmacoepigenomics and the pharmacogenomics of epigenetic drugs. The readers will gain insight into i) the classification of epigenetic drugs; ii) the mechanisms by which these drugs might be useful in AD; iii) the pharmacological properties of selected epigenetic drugs; iv) pharmacoepigenomics and the influence of epigenetic drugs on genes encoding CYP enzymes, transporters and nuclear receptors; and v) the genes associated with the pharmacogenomics of anti-dementia drugs.Expert opinion: Epigenetic drugs reverse epigenetic changes in gene expression and might open future avenues in AD therapeutics. Unfortunately, clinical trials with this category of drugs are lacking in AD. The authors highlight the need for pharmacogenetic and pharmacoepigenetic studies to properly evaluate any efficacy and safety issues. © 2014 Informa UK, Ltd. Source

Perez-Ruiz F.,Hospital Universitario Cruces | Herrero-Beites A.M.,Hospital de Gorliz | Carmona L.,Camilo Jose Cela University
Arthritis and Rheumatism | Year: 2011

Objective It is commonly accepted that the target serum urate level in patients receiving urate-lowering therapy for dissolution of urate crystals in hyperuricemia of gout is <6 mg/dl, and that patients with gout should continue urate-lowering therapy for the rest of their lives. This study was undertaken to reevaluate whether this stringent therapeutic target to dissolve crystals must be maintained lifelong to prevent new crystal formation. Methods In a prospective cohort of 211 patients with gout, urate-lowering therapy was withdrawn after 5 years if no tophus was present at baseline, or 5 years after resolution of the last tophus. Data on recurrence of gout and on serum urate levels and other potentially associated variables were analyzed. Results Multivariate regression analysis of time to crystal-proven recurrence of gout showed that serum urate levels during urate-lowering treatment and after its withdrawal were independently related to gout recurrence. None of the patients who had average serum urate levels of <7 mg/dl after urate-lowering therapy withdrawal developed a crystal-proven recurrence of gout. Post hoc analysis showed that weight loss and use of drugs that lower serum urate, such as losartan or fenofibrate, were associated with serum urate levels of <7 mg/dl during followup after urate-lowering therapy withdrawal; use of diuretics was associated with failure to achieve serum urate levels of <7 mg/dl during followup. Conclusion Our data support the hypothesis that after appropriate long-term treatment of hyperuricemia in gout with urate crystal dissolution being the therapeutic target, lifelong treatment can be targeted to achieve serum urate levels just below the threshold for saturation to avoid new crystal formation, similar to cleaning a dirty dish: more is required to get it clean than to keep it clean. © 2011 by the American College of Rheumatology. Source

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