Development of an in vitro model for vascular injury with human endothelial cells.

The aim of the present work was to establish an in vitro screening assay for drug candidates using human endothelial cells as a model for vascular injury after intravenous application. Different endpoints for viability and functionality of endothelial cells were investigated in human umbilical vein endothelial cells (HUVEC) and in immortalised human endothelial cells (IVEC). Cellular viability was determined by measuring ATP content and by the AlamarBlue assay.

Physiologically based pharmacokinetic (PBPK) modeling of disposition of epiroprim in humans.

The objective of this study was to use in synergy physiologically based and empirical approaches to estimate the drug-specific input parameters of PBPK models of disposition to simulate the plasma concentration-time profile of epiroprim in human. The estimated input parameters were the tissue:plasma partition coefficients (Pt:p) for distribution and the blood clearance (CL) for the in vivo conditions. Epiroprim represents a challenge for such methods, because it shows large interspecies differences in its pharmacokinetic properties.

Diabetic KKAy mice exhibit increased hepatic PPARgamma1 gene expression and develop hepatic steatosis upon chronic treatment with antidiabetic thiazolidinediones.

Background/aims: Peroxisome proliferator-activated receptor-gamma, which is involved in the regulation of lipid homeostasis, is upregulated in the liver of obese and diabetic mice, but the biological consequences of this induction are largely unknown. This study was aimed at further characterizing this upregulation and exploring the downstream biological effects of specific activators on hepatic lipid metabolism.

Methods: Hepatic expression of peroxisome proliferator-activated receptor-gamma1 and gamma2 mRNA and protein was analyzed by real-time polymerase chain reaction and Western immunoblotting in KKAy mice and ob/ob mice.

Effects of the oral antidiabetic repaglinide on the reproduction of rats.

Repaglinide (CAS 135062-02-1), a biguanide, is an orally available insulin secretagogue (beta-cell stimulant) and has been developed for the treatment of Type II diabetes. The developmental toxicity of the compound was investigated in rats. The effects on fertility, on embryo- and fetogenesis and on peri- and postnatal development were investigated.

Down-regulation by troglitazone of hepatic tumor necrosis factor-alpha and interleukin-6 mRNA expression in a murine model of non-insulin-dependent diabetes.

Troglitazone, a novel thiazolidinedione drug used to treat non-insulin-dependent diabetes mellitus, is a selective ligand for the peroxisome proliferator-activated receptor-gamma (PPARgamma). Recent results indicate that PPARgamma activation by thiazolidinediones regulates adipose tissue- and monocyte/peritoneal macrophage-derived cytokine expression in vitro. We evaluated whether troglitazone may also negatively regulate cytokine expression in the liver, which harbors the majority of the body's resident macrophages but which only weakly expresses PPARgamma.