Transdermal Detection of MB-102 and Correlation to Meropenem Pharmacokinetics During Continuous Renal Replacement Therapy: In Vivo Results.

Critically ill patients undergoing continuous renal replacement therapy (CRRT) have medical conditions requiring extensive pharmacotherapy. Continuous renal replacement therapy impacts drug disposition. Few data exist regarding drug dosing requirements with contemporary CRRT modalities and effluent rates.

Characterization of MB-102, a New Fluorescent Tracer Agent for Point-of-Care Renal Function Monitoring.

MB-102 is a fluorescent tracer agent designed for measurement of point-of-care glomerular filtration rate (GFR) and is currently in clinical studies. MB-102 possesses a strong UV absorbance at 266 nm and 435 nm, and broad fluorescent emission at ~560 nm when excited at ~440 nm. The MB-102 formulation is stable at 2°C-8°C for >3 years.

Transdermal fluorescence detection of a dual fluorophore system for noninvasive point-of-care gastrointestinal permeability measurement.

The intestinal mucosal barrier prevents macromolecules and pathogens from entering the circulatory stream. Tight junctions in this barrier are compromised in inflammatory bowel diseases, environmental enteropathy, and enteric dysfunction. Dual sugar absorption tests are a standard method for measuring gastrointestinal integrity, however, these are not clinically amenable.

Metabolism and action of proteasome inhibitors in primary human hepatocytes.

Proteasome inhibitors are important tools for studying the roles of the proteasome in cellular processes. In this study, we observed that the proteasome inhibitors N-benzoyloxycarbonyl (Z)-Leu-Leu-leucinal (MG132), epoxomicin, and lactacystin were ineffective and bortezomib was completely effective in inhibiting cytokine-stimulated nitric oxide production in primary cultures of human hepatocytes that had been treated with the cytochrome P450 inducer phenobarbital. The inefficacy of MG132 was due to its metabolism by CYP3A enzymes, as deduced from its rapid, ketoconazole-sensitive clearance by pooled human liver microsomes and cultured hepatocytes.

Expression and characterization of functional dog flavin-containing monooxygenase 3.

Mammalian flavin-containing monooxygenase (FMO) enzymes catalyze oxidation at nucleophilic, heteroatom centers and are important for drug, xenobiotic, and endogenous substrate metabolism. In human liver, human FMO3 (hFMO3) is the most abundant FMO isoform and is known to contribute to the hepatic clearance of a variety of clinical drugs. The purpose of the current study was to express and compare the dog (beagle) FMO3 (dFMO3) to hFMO3.

Impact of genetics and environment on nutritional and metabolite components of maize grain.

The Organization for Economic Co-operation and Development (OECD) recommends the measurement of specific plant components for compositional assessments of new biotechnology-derived crops. These components include proximates, nutrients, antinutrients, and certain crop-specific secondary metabolites. A considerable literature on the natural variability of these components in conventional and biotechnology-derived crops now exists.

Metabolite analyses of grain from maize hybrids grown in the United States under drought and watered conditions during the 2002 field season.

Understanding natural variation in the composition of conventional crop germplasms is critical in establishing a baseline for comparison of biotechnology-derived crops. This is particularly relevant to such traits as tolerance to drought stress. Thus, there is both a need to understand the contribution of stress conditions to natural variation in plant nutritional components and to determine whether levels of small molecule metabolites such as osmoprotectants and stress metabolites are also affected.