Publication Date: 2012.
Context. A large amount of magnetized plasma is frequently ejected from the Sun as coronal mass ejections (CMEs). Some of these ejections are detected in the solar wind as magnetic clouds (MCs) that have flux rope signatures. Aims. Magnetic clouds are structures that typically expand in the inner heliosphere. We derive the expansion properties of MCs in the outer heliosphere from one to five astronomical units to compare them with those in the inner heliosphere. Methods. We analyze MCs observed by the Ulysses spacecraft using in situ magnetic field and plasma measurements. The MC boundaries are defined in the MC frame after defining the MC axis with a minimum variance method applied only to the flux rope structure. As in the inner heliosphere, a large fraction of the velocity profile within MCs is close to a linear function of time. This is indicative of a self-similar expansion and a MC size that locally follows a power-law of the solar distance with an exponent called ζ. We derive the value of ζ from the in situ velocity data. Results. We analyze separately the non-perturbed MCs (cases showing a linear velocity profile almost for the full event), and perturbed MCs (cases showing a strongly distorted velocity profile). We find that non-perturbed MCs expand with a similar non-dimensional expansion rate (ζ = 1.05 ± 0.34), i.e. slightly faster than at the solar distance and in the inner heliosphere (ζ = 0.91 ± 0.23). The subset of perturbed MCs expands, as in the inner heliosphere, at a significantly lower rate and with a larger dispersion (ζ = 0.28 ± 0.52) as expected from the temporal evolution found in numerical simulations. This local measure of the expansion also agrees with the distribution with distance of MC size, mean magnetic field, and plasma parameters. The MCs interacting with a strong field region, e.g. another MC, have the most variable expansion rate (ranging from compression to over-expansion). © 2012 ESO.
Author affiliation: Gulisano, A.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Author affiliation: Dasso, S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Keywords: Interplanetary medium; Magnetic fields; Magnetohydrodynamics (MHD); Solar wind; Sun: coronal mass ejections (CMEs); Astronomical units; Coronal mass ejection; Expansion properties; Expansion rate; Flux ropes; Heliospheres; In-situ; Interplanetary medium; Linear functions; Linear velocity; Magnetic clouds; Magnetized plasmas; Mean magnetic field; Minimum variance; Outer heliosphere; Plasma measurement; Plasma parameter; Power-law; Self-similar; Strong field; Sun: coronal mass ejection; Temporal evolution; Ulysses spacecraft; Velocity profiles; Magnetic fields; Magnetohydrodynamics; Magnetoplasma; Rope; Solar system; Solar wind; Velocity.
Repository: Biblioteca Digital (UBA-FCEN). Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales
Publication Date: 2013.
Background: Bioavailability (F) and clearance (CL) are two pharmacokinetic parameters difficult to differentiate from simple plasma measurement when a drug is administered orally. Venous (V) / artery (A) concentration ratio of a drug could be a reliable index of its CL if measurements of plasma concentration were performed during a period of time where the absorption process was not longer operative, then during a pure elimination phase. Objective: A novel subrogate using two protocolized saliva samples sequentially collected (first, S1, and second, S2) was designed in order to replace V and A free plasma drug concentrations, respectively. Two drugs, phenytoin (PHT) and carbamazepine (CBZ), which are well-known for their inducer properties and their dose-dependent clearance variations, were studied taking into account the sex of individuals. Setting and patients: A multicentre two-phase collaborative study was done. The first phase was performed with healthy volunteers in order to determine salivary pharmacokinetic parameters after single dose administration. Twelve volunteers (6 male and 6 female) received 400 mg of CBZ (2 tablets x 200 mg, immediate release product). Twenty four volunteers (10 male and 14 female) received 100 mg of PHT. The second phase was carried out with epileptic patients under CBZ (11 male 15 female) or PHT (11 male and 11 female) monotherapy, in order to study dose-related and sex-related pharmacokinetic differences. Main outcome measures: In the single dose trials, peaks (Tmax, Cmax) were computed directly from the data. Areas under concentrationtime curves (AUC∞), AUC∞xW (area corrected by weight) and half-lives (t1/2) were calculated. In the case of CBZ, AUCCBZ-10,11- epoxide/AUCCBZ metabolic ratios were also calculated. After multiple dose administration, S1 and S2 trough morning drug concentrations were measured. Results: Cmax and AUC differed significantly between sexes for the two drugs after single dose administration. Nevertheless, the apparent clearance (CL/F) per unit of body weight did not differ (CBZ) or slightly differed (PHT) between sexes. Higher metabolic ratio for CBZ in women would lead to lower F and therefore lower CL in this gender. In the case of PHT, women would have either lower F or higher CL than men. After multiple dose administration, S1/S2 saliva drug concentration ratio correlated positively with S2 for CBZ, showing that CBZ clearance increases with daily dose. Gender differences were also observed for CBZ-10,11-epoxide concentration, being bioavailability the main parameter responsible for this difference. S1/S2 saliva PHT concentration ratio correlated negatively with S2, showing that PHT clearance diminishes with dose as it has been previously reported. Since a significant difference was found for S1/S2 ratio between male and females, CL is the pharmacokinetic parameter influenced by gender in PHT disposition. Conclusion: S1/S2 saliva drug concentration ratio was sensitive enough for detecting systemic clearance changes. Both CBZ and PHT would modify their bioavailability and clearance by inducing efflux transporter throughout chronic treatments, from the first dose to multiple dose administration.
Author affiliation: Fagiolino, Pietro. Universidad de la República. Facultad de química. Departamentos de Ciencias Farmaceuticas; Uruguay
Author affiliation: Vazquez, Marta. Universidad de la República. Facultad de química. Departamentos de Ciencias Farmaceutica; Uruguay
Author affiliation: Maldonado, Cecilia. Universidad de la República. Facultad de química. Departamentos de Ciencias Farmaceutica; Uruguay
Author affiliation: Ruiz, María Esperanza. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Catedra de Control de Calidad de Medicamentos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico La Plata. Centro de Investigación y Desarrollo en Ciencias Aplicadas; Argentina
Author affiliation: Volonté, Maria Guillermina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biologicas. Catedra de Control de Calidad de Medicamentos; Argentina
Author affiliation: Orozco Suárez, Sandra. Centro Medico Nacional Siglo XXI del Instituto Mexicano del Seguro Social; México
Author affiliation: Lazarowski, Alberto Jorge. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Bioquímica Clínica; Argentina
Repository: CONICET Digital (CONICET). Consejo Nacional de Investigaciones Científicas y Técnicas