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The aim of this study was to characterize insulin-stimulated skeletal muscle glucose metabolism in Zucker fatty rats and to provide insight into the therapeutic mechanism by which rosiglitazone increases insulin-stimulated glucose disposal in these rats. Metabolic parameters were measured using combined in vivo (13)C nuclear magnetic resonance (NMR)(More)
A single spot urine collection to measure the ratio of 6 beta-hydroxycortisol (6 beta-OHC) to free cortisol (C) has been proposed as a research tool for the assessment of CYP3A4 induction. However, intraindividual variability in 6 beta-OHC/C under basal conditions and conditions of induction has not been prospectively evaluated, and findings on the(More)
Continuous improvement in bioanalytical method development is desired in order to ensure the quality of the data and to better support pharmacokinetic (PK) and safety studies of biotherapeutics. One area that has been getting increasing attention recently is in the assessment of “free” and “total” analyte and the impact of the assay format on those(More)
Human antibody, induced by a vaccine consisting of undegraded and highly purified extracellular type III-specific polysaccharide of group B streptococcus, was shown to increase the rate of phagocyte-mediated killing of bacteria of the homologous type. The bactericidal effect was mediated by type III-specific antibody and was complement dependent. An assay(More)
For therapeutic monoclonal antibodies (mAbs) against soluble ligands, the free ligand level can, theoretically, be used as a surrogate for efficacy. However, it can be extremely challenging technically to measure free ligand level in the presence of an excessive amount of antibody–ligand complex. The interplay among such mAbs, ligands, and the downstream(More)
For biotherapeutics directed against soluble targets, most often monoclonal antibodies (mAbs), their therapeutic efficacy theoretically is driven by the magnitude and duration of free target suppression. However, for soluble targets of rapid turnover and low abundance, it can be technically challenging to directly measure the lowering of free target(More)
Therapeutic monoclonal antibodies (mAbs) possess a high degree of heterogeneity associated with the cell expression system employed in manufacturing, most notably glycosylation. Traditional immunoassay formats used to quantify therapeutic mAbs are unable to discriminate between different glycosylation patterns that may exist on the same protein amino acid(More)
Sera obtained from human volunteers at 6 weeks after vaccination with highly purified type III polysaccharide antigen prepared from a group B Streptococcus, strain M732, were found to protect neonatal rats from otherwise lethal infection by the homologous strain. The specific antibody content of the sera, expressed in micrograms of antibody protein per(More)
Study the disposition and target-neutralization capability of an anti-interleukin-6 (IL-6) monoclonal antibody (mAb) at the joint in a mouse collagen-induced arthritis (CIA) model. A mechanistic pharmacokinetic/pharmacodynamic study was conducted in a mouse CIA model using CNTO 345, a rat anti-mouse IL-6 mAb, as model compound. The drug, total/free IL-6(More)
Stable isotopes are commonly used as tracers for the measurement of glycerol and glucose kinetics in metabolic studies. Traditionally, the analysis of these isotopes has been performed using gas chromatography-mass spectrometry, which requires that the analytes first be derivatized. The derivatization process adds considerable complexity to the method.(More)