Background: Air pollution is associated with negative health effects. Exposure to combustion-derived particulate matter (PM) air pollution has been related to increased incidence of cardiovascular and respiratory morbidity and mortality, specifically in susceptible populations. Ambient particles, with a diameter of less than 2.5 mm, have been suggested to be the strongest contributor to these health effects. Diesel exhaust (DE) is a major source of small combustion-derived PM air pollution world wide.  In healthy volunteers, exposure to DE, has been associated with airway inflammation and impaired vasomotor function and endogenous fibrinolysis. The aims of this thesis were to further elucidate the underlying mechanisms to the reported cardiovascular effects following exposure to DE, with specific focus on endothelin-1 (ET-1). Additionally, the vascular effects of the major gaseous component of DE, nitrogen dioxide (NO2), were assessed together with the impact of an exhaust particle trap to reduce the observed negative vascular effects after DE exposure. Methods: In all studies healthy, non-smoking male volunteers were included and exposed for one hour during intermittent exercise in a randomised double-blind crossover fashion. In studies I-III, subjects were exposed to DE at a particulate matter concentration of approximately 300 μg/m3 and filtered air, on two different occasions. In study V an additional exposure was employed, during which DE was filtered through an exhaust particle trap. In study IV subjects were exposed to nitrogen dioxide (NO2) at 4 ppm or filtered air. In study I, thrombus formation and platelet activation were assessed using the Badimon ex vivo perfusion chamber and flow cytometry. Study II comprised the determination of arterial stiffness including pulse wave analysis and velocity. In studies III-V, vascular assessment was performed using venous occlusion plethysmography. In studies IV and V, the vascular responses to intra-arterially infused endothelial-dependent and endothelial-independent vasodilatators were registered. In study III, vascular responses to intra-arterial infusion of Endothelin-1 (ET-1) and ET-1-receptor antagonists were assessed. Venous occlusion phlethysmography was in all cases performed 4-6 hours following exposures. Blood samples for markers of inflammation, coagulation and platelet activation were collected before and throughout the study periods in studies III and V. Results: Exposure to DE increased ex vivo thrombus formation and arterial stiffness, in terms of augmentation index. DE inhalation impaired vasomotor function and endogenous fibrinolysis. The exhaust particle trap reduced the particle concentration by 98% and abolished the effects on vasomotor function, endogenous fibrinolysis and ex vivo thrombus formation. Plasma concentrations of ET-1 and its precursor big-ET-1 were unchanged following exposure. Dual endothelial receptor antagonism caused similar vasodilatation after both exposures, although vasodilatation to the endothelin-A receptor alone was blunted after DE exposure. ET-1 infusion induced vasoconstriction only following DE exposure. Exposure to nitrogen dioxide did not affect vascular function. Conclusion: Inhalation of diesel exhaust in young healthy men impaired important and complementary aspects of vascular function in humans; regulation of vascular tone and endogenous fibrinolysis as well as increased ex vivo thrombus formation. The use of an exhaust particle trap significantly reduced particle emissions and abolished the DE-induced vascular and prothrombotic effects. The adverse vascular effects following DE exposure do not appear to be directly mediated through the endothelin system. Neither is NO2 suggested to be a major arbiter of the DE-induced cardiovascular responses. Arterial stiffness is a non-invasive and easily accessible method and could thus be employed to address vascular function in larger field studies. Taken together, this thesis has given further knowledge about the mechanisms underlying the DE-induced vascular effects.

Diss. (sammanfattning) Umeå : Umeå universitet, 2009. / Härtill 5 uppsatser. Även tryckt utgåva.

L'objectif principal de cette thèse est de proposer de nouveaux mécanismes de transport de solides dans les disques protoplanétaires afin de résoudre le problème de la dérive radiale des solides causée par la friction du gaz. En effet, malgré d'importants efforts théoriques et expérimentaux, il reste difficile à expliquer comment de petites particules de poussière submillimétriques forment des blocs kilométriques dans les conditions qui règnent au sein des disques protoplanétaires. Je montre que les mécanismes de transport proposés dans cette thèse sont en mesure de résoudre ce problème de dérive et j'étudie leurs effets sur la formation des premiers solides. Dans un premier temps, je considère les effets de la photophorèse et des jets magnétiques sur le mouvement radial des grains dans les disques protoplanétaires. Le premier est dû aux effets thermiques du rayonnement stellaire sur la surface des grains, tandis que le deuxième est provoqué par les lignes de champ magnétique stellaire qui traversent le disque. Les résultats sont obtenus en résolvant les équations du mouvement des particules de façon numérique. Le transport induit par ces mécanismes a d'importantes conséquences pour la composition des météorites qui sont discutées dans le contexte de la nébuleuse solaire. Dans un deuxième temps, j'étudie la formation de pièges à particules causés par la présence de plusieurs planètes dans le disque grâce à des simulations hydrodynamiques. Ces résultats incluent la croissance des grains et sont directement comparés aux travaux similaires considérant une seule planète dans le disque. Le cas de l'étoile HD 100546, pour lequel les observations récentes suggèrent la présence de deux planètes dans le disque, est examiné en détail. L'évolution du disque en considérant différentes tailles de grain est étudiée au moyen de simulations hydrodynamiques SPH. Les distributions de la poussière et du gaz dans le disque sont particulièrement révélatrices car elles permettent de mettre à l'épreuve les différents scenarios proposés par les observations. L'étude de ces mécanismes montre que, selon leur taille et leur composition, les grains s'accumulent à différentes distances radiales dans le disque. Ces processus empêchent donc l'accrétion des solides par l'étoile et résolvent ainsi le problème de la barrière de dérive radiale. Les futures observations avec des instruments tels que ALMA, SPHERE et MATISSE permettront de mieux contraindre l'efficacité de ces mécanismes dans les disques protoplanétaires / The main goal of this work is to study new transport mechanisms of solids in protoplanetary disks and its implications for the composition of the first solids. The motion of solids inside the disk leads to the so-called radial-drift barrier caused by the gas aerodynamic drag, which is a severe problem for planet formation theory. In this context, it is hard to explain how sub-mm grains reach planetesimal sizes during the disk lifespan. First of all, I study the effects of photophoresis on the dust grains illuminated by the stellar radiation and quantify the efficiency of radial transport as a function of the particle properties. Then, I study the ejection of particles from the inner regions of the disk via the so-called stellar fountain model. Due to the stellar magnetic field which threads the disk, solid particles enter a jet that sends them outwards up to a few astronomical units. Both processes, photophoresis and jets, have important implications for the composition of meteorites which are discussed within the Solar Nebula scenario. In the last chapter, I study dust dynamics in multi-planetary systems through SPH simulations. The formation of particle traps in a disk with two planets is treated in detail and compared to previous work considering a single planet. Then I consider the case of HD 100546, a star with a disk which might harbor two planets according to recent observations, and study the disk evolution in different scenarios. By considering different grains sizes it is then possible to establish a link with interferometric observations of the system. We consider models with different planetary masses and radial distances in order to better constrain these quantities. The study of these mechanisms reveals that, according to particle size and composition, grains can pile up at different radial distances in the disk. This prevents the accretion by the central star by stopping the radial drift of solids, which shows that these mechanisms are good candidates to solve the radial-drift barrier. Future observations using ALMA, SPHERE and MATISSE will provide insights into the efficiency of these transport processes in protoplanetary disks