Impact of aldosterone synthase inhibitor FAD286 on steroid hormone profile in human adrenocortical cells.

Inhibition of aldosterone synthase (CYP11B2) is an alternative treatment option to mineralocorticoid receptor antagonism to prevent harmful aldosterone effects. FAD286 is the best characterized aldosterone synthase inhibitor. However, to date, no study has used sensitive liquid chromatography-tandem mass spectrometry to characterize in detail the effect of FAD286 on the secreted steroid hormone profile of adrenocortical cells. Basal aldosterone production in NCI-H295R cells was detectable and 9-fold elevated after stimulation with angiotensin II. FAD286 inhibited this increase, showing a maximal effect at 10 nmol/l. Higher concentrations of FAD286 did not further reduce aldosterone concentrations, but showed a parallel reduction in corticosterone, cortisol and cortisone levels, reflecting additional inhibition of steroid-11 beta-hydroxylase (CYP11B1). Pregnenolone, progesterone and 17-OH-progesterone levels remained unaffected. In conclusion, the aldosterone synthase inhibitor FAD286 lowers angiotensin II-induced aldosterone concentrations in adrenocortical cells but the relative lack of selectivity over CYP11B1 is evident at higher FAD286 concentrations

A mortar approach for Fluid-Structure interaction problems: Immersed strategies for deformable and rigid bodies

This paper proposes a new Fluid-Structure Interaction immersed computational framework. The coupling between an underlying incompressible fluid and an embedded solid is formulated by means of the overlapping domain decomposition method in conjunction with a mortar approach, leading to a variationally consistent scheme which is capable of unifying a range of methodologies currently available in the literature. This novel framework provides great flexibility and enables the modelling of immersed deformable solids (compressible and incompressible) as well as rigid bodies through the use of a weak director based formulation. A novel Null-Space reduction scheme is employed in order to enhance the conditioning of the resulting system of equations and reduce the computational cost. An implicit structure preserving time integration algorithm is used to yield extra stability and robustness and the use of a segmentation technique near the boundary between fluid and solid also leads to enhanced accuracy. The methodology is benchmarked against results obtained by using alternative boundary fitted methodologies