Mast cell-mediated immune modulation in experimental Rheumatoid Arthritis and Atherosclerosis

In dit proefschrift hebben wij de invloed van mestcellen in dierexperimentele modellen voor reumatoïde artritis en aderverkalking bestudeerd met een focus op de rol van mestcellen in de (sub)-klinische fases van het ziekteproces, waarin er een actieve immuunrespons ontwikkeld was. Ook hebben wij de aanwezigheid van verschillende soorten antistoffen in het serum van cardiovasculaire patiënten onderzocht. Wij hebben de niveaus van antilichamen gecorreleerd aan klinische observaties zoals body mass index (BMI), lipidenprofiel, klinische diagnose van vaatlijden, samenstelling van de atherosclerotische plaque en de uitkomst van de ziekte

Effect of Vortex Generators on NREL Wind Turbine: Aerodynamic Performance and Far-Field Noise

Passive flow separation control with vortex generators (VG) is actively used over the wind turbine blade. In this paper, the effect of vortex generators is simulated on a full-scale 2-blade wind-turbine tested at the National Renewable Energy Laboratory. The simulation is performed using Very-Large-Eddy/Lattice-Boltzmann method (VLES/LBM). The analysis focuses on the effect of vortex generators on the aerodynamic performance and far-field noise. The simulation results without vortex generators are compared with the experimental results, reaching good agreement. The vortex generators produce counter-rotating vortices in the wake which effectively delay flow separation, leading to better aerodynamic performance. The acoustic analysis indicates that the dominant noise sources are the tonal noise produced by the flow separation and the turbulent-boundary-layer trailing-edge noise. Similar noise levels are obtained for the configurations with and without vortex generators

Mimicking the cardiac cycle in intact cardiomyocytes using diastolic and systolic force clamps; measuring power output

A single isolated cardiomyocyte is the smallest functional unit of the heart. Yet, all single isolated cardiomyocyte experiments have been limited by the lack of proper methods that could reproduce a physiological cardiac cycle. We aimed to investigate the contractile properties of a single cardiomyocyte that correctly mimic the cardiac cycle.By adjusting the parameters of the feedback loop, using a suitably engineered feedback system and recording the developed force and the length of a single rat cardiomyocyte during contraction and relaxation, we were able to construct force-length (FL) relations analogous to the pressure-volume (PV) relations at the whole heart level. From the cardiac loop graphs, we obtained, for the first time, the power generated by one single cardiomyocyte.Here, we introduce a new approach that by combining mechanics, electronics, and a new type optical force transducer can measure the FL relationship of a single isolated cardiomyocyte undergoing a mechanical loop that mimics the PV cycle of a beating heart

The influence of a Mediterranean Diet with and without Red Wine on the Haemostatic and Inflammatory Parameters of Subjects with the Metabolic Syndrome

This 8 week study examined whether a Mediterranean diet supplemented with red wine, had an acute impact onsubjects diagnosed with the metabolic syndrome. Twelve non-smoking subjects with diagnostic criteria of themetabolic syndrome on minimal medication, consumed a Mediterranean-like diet for 4 weeks respectively withoutand with red wine. The amount of red wine consumed was 250 ml (26 grams of alcohol) per day for male and 180ml (19 grams) per day for female participants. A nutrigenetic profile for cardiovascular risk factors was performedon each participant. Fasting blood specimens were taken at baseline, after the diet and after the diet with wineinterventions for platelet function, procoagulants FVII and FVIII, von Willebrand’s factor, fibrinogen, tissueplasminogen activator, plasminogen activator inhibitor-1, highly sensitive C-reactive protein and oxygen radicalabsorbance capacity (ORAC). After both periods of diet without wine and with wine, ORAC increased significantlycompared to baseline levels. Except for platelet H2O2 fluxes and FVII concentration, none of the haemostatic orinflammatory parameters changed significantly after the intervention periods compared with baseline levels.Genetic risk factors for cardiovascular disease were identified in all study participants and the potential genotypiceffects relevant to this study were generally in agreement with expected phenotypic response following the dietaryintervention. Our conclusions are that the period of intervention was too short for substantial changes inhaemostatic or in inflammatory parameters in subjects who already manifest some changes in their cardiovascularsystem and who showed diverse genetic profiles underlying increased cardiovascular risk

Unraveling the Genotype-Phenotype Relationship in Hypertrophic Cardiomyopathy:Obesity-Related Cardiac Defects as a Major Disease Modifier

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy and is characterized by asymmetric septal thickening and diastolic dysfunction. More than 1500 mutations in genes encoding sarcomere proteins are associated with HCM. However, the genotype-phenotype relationship in HCM is incompletely understood and involves modification by additional disease hits. Recent cohort studies identify obesity as a major adverse modifier of disease penetrance, severity, and clinical course. In this review, we provide an overview of these clinical findings. Moreover, we explore putative mechanisms underlying obesity-induced sensitization and aggravation of the HCM phenotype. We hypothesize obesity-related stressors to impact on cardiomyocyte structure, metabolism, and homeostasis. These may impair cardiac function by directly acting on the primary mutation-induced myofilament defects and by independently adding to the total cardiac disease burden. Last, we address important clinical and pharmacological implications of the involvement of obesity in HCM disease modification.</p