Prediction of clinical drug-drug interactions of veliparib (ABT-888) with human renal transporters (OAT1, OAT3, OCT2, MATE1, and MATE2K).

Veliparib (ABT-888) is largely eliminated as parent drug in human urine (70% of the dose). Renal unbound clearance exceeds glomerular filtration rate, suggesting the involvement of transporter-mediated active secretion. Clinically relevant pharmacokinetic interactions in the kidney have been associated with OAT1, OAT3, OCT2, MATE1, and MATE2K.

AhR activation underlies the CYP1A autoinduction by A-998679 in rats.

Xenobiotic-mediated induction of cytochrome P450 (CYP) drug metabolizing enzymes (DMEs) is frequently encountered in drug discovery and can influence disposition, pharmacokinetic, and toxicity profiles. The CYP1A subfamily of DMEs plays a central role in the biotransformation of several drugs and environmental chemicals. Autoinduction of drugs through CYP3A enzymes is a common mechanism for their enhanced clearance.

Protective immunization in mice against group B streptococci using encapsulated C5a peptidase.

Objective: The purpose of the study was to test whether C5a peptidase encapsulated within a biodegradable polymer can act as a vaccine and elicit an immune response to prevent group B streptococci (GBS) infection in mice and provide protection to pups.

Study Design: C5a peptidase was encapsulated in semipermeable microspheres of poly(lactide-co-glycolide). Female ICR mice were immunized with encapsulated C5a peptidase, free C5a peptidase, or empty microparticles.

Can myoglobin expression in pancreatic beta cells improve insulin secretion under hypoxia? An exploratory study with transgenic porcine islets.

The feasibility of myoglobin (Mb)-facilitated oxygen transport in improving porcine islet survival under hypoxia was investigated. Discrete groups of islets were transfected with replication-defective adenoviral vector Ad5 respiratory syncitial virus (RSV) to induce expression of Mb or green fluorescent protein (GFP). Native islets served as the controls.

Characterizing short-term release and neovascularization potential of multi-protein growth supplement delivered via alginate hollow fiber devices.

Multi-protein (10-250 kDa) endothelial cell growth supplement (ECGS) contains growth factors of varying sizes resulting in advanced release rates from diffusion-based drug delivery devices. As a result, the biochemical stimulus provided by ECGS for neovascularization in the critical initial stages of cell transplantation in artificial organs may differ from that for single growth factor delivery. In this study, both in vitro and in vivo studies were conducted with ECGS to correlate in vitro release of multiple angiogenic growth factors to vascularization potential in vivo.