Montero D.,University of Avignon |
Montero D.,Universiteitssingel 50 |
Montero D.,Cardiovascular Research Institute Maastricht CARIM |
Vinet A.,University of Avignon |
Roberts C.K.,University of California at Los Angeles
International Journal of Cardiology | Year: 2015
Background While aerobic exercise training may decrease arterial stiffness, the impact of combined aerobic and resistance training is unclear. Therefore, the aim of this study was to systematically review and quantify the effect of combined aerobic and resistance training on arterial stiffness, as determined by arterial pulse wave velocity (PWV), and compare it with aerobic training.Methods MEDLINE, EMBASE and Web of Science were searched through November 2013 for randomized controlled trials evaluating the effect of aerobic or combined aerobic and resistance training on PWV. A meta-analysis was performed to determine the standardized mean difference (SMD) in PWV between exercise and control groups. Subgroup analyses were used to study potential moderating factors.Results Twenty-one randomized controlled trials comparing exercise and control groups (overall n = 752), met the inclusion criteria. After data pooling, PWV was decreased in aerobic trained groups compared with controls (10 trials, SMD = - 0.52, 95% CI = - 0.76, - 0.27; P < 0.0001) but did not reach statistical significance in combined trained groups compared with controls (11 trials, SMD = - 0.23, 95% CI = - 0.50, 0.04; P = 0.10). The effect in aerobic trained groups did not differ compared with combined trained groups (P = 0.12). In addition, aerobic training resulted in significantly lower SMD in PWV compared with combined training in interventions including a higher volume of aerobic training or assessing carotid-femoral PWV.Conclusions These data suggest that combined aerobic and resistance training interventions may have reduced beneficial effects on arterial stiffness compared with control interventions, but do not appear to differ significantly with aerobic training alone. © 2014 Elsevier Ireland Ltd. All rights reserved.
Hamani C.,Center for Addiction and Mental Health |
Hamani C.,Toronto Western Hospital |
Temel Y.,Maastricht University |
Temel Y.,Universiteitssingel 50
Science Translational Medicine | Year: 2012
During treatment with deep brain stimulation (DBS), electrical current is delivered into the brain parenchyma through implanted electrodes. Although this technique is routinely used in the treatment of Parkinson's disease, essential tremor, and dystonia, a growing number of neuropsychiatric applications for DBS are being investigated. Investigators can use animal models of these diseases to study the mechanisms through which DBS exerts its effects, to explore new applications of this therapy, and to identify and characterize alternative stimulation targets. Here, we discuss preclinical DBS research that provides insight into the mechanisms underlying cognitive and psychiatric applications of this technique, emphasizing the predictive validity of animal models and their potential use in translational research.
Schurgers L.J.,Universiteitssingel 50 |
Uitto J.,Thomas Jefferson University |
Reutelingsperger C.P.,Universiteitssingel 50
Trends in Molecular Medicine | Year: 2013
Vascular mineralization has recently emerged as a risk factor for cardiovascular morbidity and mortality. Previously regarded as a passive end-stage process, vascular mineralization is currently recognized as an actively regulated process with cellular and humoral contributions. The discovery that the vitamin K-dependent matrix Gla-protein (MGP) is a strong inhibitor of vascular calcification has propelled our mechanistic understanding of this process and opened novel avenues for diagnosis and treatment. This review focuses on molecular mechanisms of vascular mineralization involving MGP and discusses the potential for treatments and biomarkers to monitor patients at risk for vascular mineralization. © 2013 Elsevier Ltd.
van den Hove D.L.A.,Maastricht University |
van den Hove D.L.A.,University of Würzburg |
van den Hove D.L.A.,Universiteitssingel 50 |
Chouliaras L.,Maastricht University |
Rutten B.P.F.,Maastricht University
Current Alzheimer Research | Year: 2012
Epigenetic modifications have been proposed to underlie age-related dysfunction and associated disorders. 5- hydroxymethylcytosine (5-hmC) is a newly described epigenetic modification. It is generated by the oxidation of 5- methylcytosine (5-mC) by the ten-eleven translocation (TET) family of enzymes. Various studies have shown that 5-hmC is present in high levels in the brain. Its lower affinity to methyl-binding proteins as compared to 5-mC suggests that it might have a different role in the regulation of gene expression, while it is also implicated in the DNA demethylation process. Interestingly, various widely used methods for DNA methylation detection fail to discriminate between 5-hmC and 5-mC, while numerous specific techniques are currently being developed. Recent studies have indicated an increase of 5-hmC with age in the mouse brain as well as an age- and gene-expression-level-related enrichment of 5-hmC in genes implicated in neurodegeneration. These findings suggest that 5-hmC may play an important role in the etiology and course of age-related neurodegenerative disorders. The present perspective summarizes the current knowledge on 5-hmC, discusses methodological challenges related to its detection, and suggests future strategies for examining the functional role of this epigenetic modification and its possible implication in aging and Alzheimer's disease. © 2012 Bentham Science Publishers.
Van Aelst L.N.L.,Catholic University of Leuven |
Van Aelst L.N.L.,University Hospitals Leuven |
Heymans S.,Catholic University of Leuven |
Heymans S.,Maastricht University |
And 2 more authors.
Journal of Cardiovascular Translational Research | Year: 2013
MicroRNAs (miRs) are short, noncoding RNAs that function as posttranscriptional inhibitors of mRNA translation to protein. They are essential for normal development and homeostasis. Dysregulated expression patterns both cause and result from disease states. Generally studied as intracellular mediators, miRs can be isolated from body fluids and exhibit remarkable stability to degradation. These features, in combination with their tissue specificity, make miRs attractive candidates as blood-derived biomarkers for coronary artery disease (CAD), the most frequent cause of death worldwide. The use of miRs as biomarkers in both symptomatic and asymptomatic CAD and the influence of conventional cardiovascular risk factors and CAD treatment on their circulating levels are the topics of this review. To conclude, it highlights the remaining hurdles to tackle before this promising application of miRs can enter into routine clinical practice. © 2013 Springer Science+Business Media New York.
Chouliaras L.,Maastricht University |
Mastroeni D.,Maastricht University |
Mastroeni D.,Banner Sun Health Research Institute |
Delvaux E.,Banner Sun Health Research Institute |
And 9 more authors.
Neurobiology of Aging | Year: 2013
Epigenetic dysregulation of gene expression is thought to be critically involved in the pathophysiology of Alzheimer's disease (AD). Recent studies indicate that DNA methylation and DNA hydroxymethylation are 2 important epigenetic mechanisms that regulate gene expression in the aging brain. However, very little is known about the levels of markers of DNA methylation and hydroxymethylation in the brains of patients with AD, the cell-type specificity of putative AD-related alterations in these markers, as well as the link between epigenetic alterations and the gross pathology of AD. The present quantitative immunohistochemical study investigated the levels of the 2 most important markers of DNA methylation and hydroxymethylation, that is, 5-methylcytidine (5-mC) and 5-hydroxymethylcytidine (5-hmC), in the hippocampus of AD patients (n = 10) and compared these to non-demented, age-matched controls (n = 10). In addition, the levels of 5-hmC in the hippocampus of a pair of monozygotic twins discordant for AD were assessed. The levels of 5-mC and 5-hmC were furthermore analyzed in a cell-type and hippocampal subregion-specific manner, and were correlated with amyloid plaque load and neurofibrillary tangle load. The results showed robust decreases in the hippocampal levels of 5-mC and 5-hmC in AD patients (19.6% and 20.2%, respectively). Similar results were obtained for the twin with AD when compared to the non-demented co-twin. Moreover, levels of 5-mC as well as the levels of 5-hmC showed a significant negative correlation with amyloid plaque load in the hippocampus (rp = -0.539, p = 0.021 for 5-mC and rp = -0.558, p = 0.016 for 5-hmC). These human postmortem results thus strengthen the notion that AD is associated with alterations in DNA methylation and hydroxymethylation, and provide a basis for further epigenetic studies identifying the exact genetic loci with aberrant epigenetic signatures. © 2013 Elsevier Inc.
Van Can J.,Universiteitssingel 50 |
Sloth B.,Novo Nordisk AS |
Jensen C.B.,Novo Nordisk AS |
Flint A.,Novo Nordisk AS |
And 2 more authors.
International Journal of Obesity | Year: 2014
Introduction: Mechanisms for liraglutide-induced weight loss are poorly understood. Objective: We investigated the effects of liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese non-diabetic individuals. Design: Participants (N=49, 18-75 years, body mass index: 30-40 kg m-2) were randomized to two of three treatments: liraglutide 1.8 mg, 3.0 mg, or placebo in a double-blind, incomplete crossover trial. After 5 weeks, 24-h energy expenditure (EE) and substrate oxidation were measured in a respiratory chamber Gastric emptying (acetaminophen absorption method), glycemic parameters and appetite were assessed during a 5-h meal test. Ad libitum energy intake during a subsequent lunch was also assessed. Results: Five-hour gastric emptying (AUC0-300 min) was found to be equivalent for liraglutide 1.8 versus 3.0 mg (primary end point), and for both liraglutide doses versus placebo, as 90% confidence intervals for the estimated treatment ratios were contained within the prespecified interval (0.80-1.25). However, 1-h gastric emptying was 23% lower than placebo with liraglutide 3.0 mg (P=0.007), and a nonsignificant 13% lower than placebo with liraglutide 1.8 mg (P=0.14). Both liraglutide doses similarly reduced fasting glucose (0.5-0.6 mmol l -1 versus placebo, P<0.0001), glucose Cmax and 1-h AUC versus placebo; only liraglutide 3.0 mg reduced iAUC0-300 min (by ~26% versus placebo, P=0.02). Glucagon iAUC0-300 min decreased by ~30%, and iAUC0-60 min for insulin and C-peptide was ~20% lower with both liraglutide doses versus placebo. Liraglutide doses similarly increased mean postprandial satiety and fullness ratings, reduced hunger and prospective food consumption and decreased ad libitum energy intake by ~16%. Liraglutide-associated reductions in EE were partly explained by a decrease in body weight. A relative shift toward increased fat and reduced carbohydrate oxidation was observed with liraglutide. Clinicaltrials.gov ID:NCT00978393. Funding: Novo Nordisk. Conclusion: Gastric emptying AUC0-300 min was equivalent for liraglutide 1.8 and 3.0 mg, and for liraglutide versus placebo, whereas reductions in 1-h gastric emptying of 23% with liraglutide 3.0 mg and 13% with 1.8 mg versus placebo were observed. Liraglutide 3.0 mg improved postprandial glycemia to a greater extent than liraglutide 1.8 mg. Liraglutide-induced weight loss appears to be mediated by reduced appetite and energy intake rather than increased EE. © 2014 Macmillan Publishers Limited All rights reserved.
Schurgers L.J.,Universiteitssingel 50
Kidney International | Year: 2013
Vascular calcification has emerged as an independent risk factor for cardiovascular morbidity and mortality, especially in chronic kidney disease. Deficiencies in calcium-regulatory proteins directly relate to development of calcifications. McCabe and colleagues report that vitamin K is a key regulator of vascular calcification, via carboxylation of vitamin K-dependent proteins such as matrix Gla protein. Knowledge about vitamin K status may propel therapeutic strategies to prevent and treat vascular calcification with high vitamin K supplementation. © 2013 International Society of Nephrology.
Schaper F.L.W.V.J.,Universiteitssingel 50 |
Reutelingsperger C.P.,Universiteitssingel 50
Cancers | Year: 2013
Evaluation of efficacy of anti-cancer therapy is currently performed by anatomical imaging (e.g., MRI, CT). Structural changes, if present, become apparent 1-2 months after start of therapy. Cancer patients thus bear the risk to receive an ineffective treatment, whilst clinical trials take a long time to prove therapy response. Both patient and pharmaceutical industry could therefore profit from an early assessment of efficacy of therapy. Diagnostic methods providing information on a functional level, rather than a structural, could present the solution. Recent technological advances in molecular imaging enable in vivo imaging of biological processes. Since most anti-cancer therapies combat tumors by inducing apoptosis, imaging of apoptosis could offer an early assessment of efficacy of therapy. This review focuses on principles of and clinical experience with molecular imaging of apoptosis using Annexin A5, a widely accepted marker for apoptosis detection in vitro and in vivo in animal models. 99mTc-HYNIC-Annexin A5 in combination with SPECT has been probed in clinical studies to assess efficacy of chemo- and radiotherapy within 1-4 days after start of therapy. Annexin A5-based functional imaging of apoptosis shows promise to offer a personalized medicine approach, now primarily used in genome-based medicine, applicable to all cancer patients. © 2013 by the authors; licensee MDPI, Basel, Switzerland.
Vrolix R.,Universiteitssingel 50 |
Mensink R.P.,Universiteitssingel 50
American Journal of Clinical Nutrition | Year: 2010
Background: Epidemiologic studies suggest that diets with a low glycemic index (GI) or glycemic load (GL) are associated with a decreased risk of developing metabolic syndrome. Intervention studies are inconsistent, however, possibly due to differences in macronutrient and fiber compositions of the experimental diets. Objective: We tested side-by-side test foods with similar macronutrient and fiber compositions but with different sucrose-flour ratios or carbohydrate source to determine the effects of different GIs and GLs on metabolic risk markers in overweight subjects. Design: Overweight men (n = 9) and women (n = 6) received in random order for 11 wk 4 test foods with an increased GI or a decreased GI (69 compared with 40, 86 compared with 48, 63 compared with 37, and 51 compared with 20, respectively). There was a GL difference of 32 units between the 2 interventions. Results: At the end of the 11-wk intervention periods, the decreased GL test foods did not change fasting plasma glucose (mean ± SD: 5.83 ± 0.6 compared with 5.94 ± 0.6 mmol/L) or insulin (8.3 ± 2.8 compared with 9.8 ± 5.1 mU/L) concentrations compared with increased GL test foods. Serum total cholesterol (5.56 ± 0.90 compared with 5.76 ± 1.04 mmol/L), LDL-cholesterol (3.57 ± 0.72 compared with 3.68 ± 0.80 mmol/L), HDL-cholesterol (1.21 ± 0.38 compared with 1.24 ± 0.37 mmol/L), and triacylglycerol (1.61 ± 0.77 compared with 1.78 ± 1.04 mmol/L) concentrations were also not significantly different for decreased and increased GL test foods, respectively. Finally, proinflammatory (high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-α, monocyte chemoattractant protein 1) and prothrombotic (plasminogen activator inhibitor 1) markers were not affected. Glucose and lipids were also analyzed after 1 and 5 wk of intervention and were not affected by the intervention. Conclusion: When incorporated into a habitual diet, consumption of test foods with a decreased GL does not ameliorate metabolic risk markers in overweight subjects. © 2010 American Society for Nutrition.