Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME.
This review encompasses the most important advances in liver functions and hepatotoxicity and analyzes which mechanisms can be studied in vitro. In a complex architecture of nested, zonated lobules, the liver consists of approximately 80 % hepatocytes and 20 % non-parenchymal cells, the latter being involved in a secondary phase that may dramatically aggravate the initial damage. Hepatotoxicity, as well as hepatic metabolism, is controlled by a set of nuclear receptors (including PXR, CAR, HNF-4α, FXR, LXR, SHP, VDR and PPAR) and signaling pathways. When isolating liver cells, some pathways are activated, e.g., the RAS/MEK/ERK pathway, whereas others are silenced (e.g. HNF-4α), resulting in…
Tailoring the axial shape of the point spread function using the Toraldo concept
A novel procedure for shaping the axial component of the point spread function of nonparaxial focusing systems by use of phase-only pupil filters is presented. The procedure is based on the Toraldo technique for tailoring focused fields. The resulting pupil filters consist of a number of concentric annular zones with constant real transmittance. The number of zones and their widths can be adapted according to the shape requirements. Our method is applied to design filters that produce axial superresolution in confocal scanning systems.