Paired EMI-HIMU hotspots in the South Atlantic-Starting plume heads trigger compositionally distinct secondary plumes?

Age-progressive volcanism is generally accepted as the surface expression of deep-rooted mantle plumes, which are enigmatically linked with the African and Pacific large low-shear velocity provinces (LLSVPs). We present geochemical and geochronological data collected from the oldest portions of the age-progressive enriched mantle one (EMI)-type Tristan-Gough track. They are part of a 30- to 40-million year younger age-progressive hotspot track with St. Helena HIMU (high time-integrated 238U/204Pb) composition, which is also observed at the EMI-type Shona hotspot track in the southernmost Atlantic. Whereas the primary EMI-type hotspots overlie the margin of the African LLSVP, the HIMU-type hotspots are located above a central portion of the African LLSVP, reflecting a large-scale geochemical zonation. We propose that extraction of large volumes of EMI-type mantle from the margin of the LLSVP by primary plume heads triggered upwelling of HIMU material from a more internal domain of the LLSVP, forming secondary plumes.

Mechanism-based PK/PD model for the lymphocytopenia induced by endogenous and exogenous corticosteroids.

OBJECTIVE: Lymphocytopenia is a sensitive surrogate marker for the immunological effects of corticosteroids. This pharmacokinetic/pharmacodynamic (PK/PD) study investigated whether the circadian variation of blood lymphocytes observed after placebo is secondary to the circadian rhythm of endogenous cortisol, and developed based on this relationship an improved PK/PD model for a more sensitive description of the effect of low-dose corticosteroid therapy on blood lymphocytes considering the net activity of the exogenous corticosteroid budesonide and endogenous cortisol. METHODS: In an open, parallel study design, 3 mg oral budesonide or placebo were given at 8.00 a.m., 4.00 p.m. and midnight to two groups of 12 volunteers. Lymphocyte counts and serum concentrations of budesonide and cortisol were monitored for 24 hours. A mechanism-based PK/PD model which considered the non-linear protein binding of cortisol and the budesonide-induced cortisol suppression was employed to relate changes in blood lymphocytes to free cortisol levels after placebo and to the net activity of free budesonide and free endogenous cortisol after active treatment. RESULTS: The circadian rhythm of blood lymphocytes observed after placebo could inversely be related to the circadian rhythm of serum cortisol. After budesonide administration, lymphocyte counts could accurately be linked to the net activity of budesonide and endogenous cortisol. The resulting EC50 values for the effect of budesonide on cortisol, budesonide on lymphocytes and cortisol on lymphocytes were 0.063 +/- 0.034, 0.22 +/- 0.13 and 26.3 +/- 15.0 ng/ml (placebo group 15.4 +/- 3.4 ng/ml), respectively. CONCLUSIONS: The presented mechanism-based PK/PD model suggests that blood lymphocytes are under physiological control of cortisol. It further indicates that endogenous and exogenous corticosteroids and their pharmacological interaction need to be considered for modeling the effects of low doses of exogenous corticosteroids on the immune system.