David E. Hibbs

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BACKGROUND AND PURPOSE Airway remodelling is a consequence of long-term inflammation and MAPKs are key signalling molecules that drive pro-inflammatory pathways. The endogenous MAPK deactivator--MAPK phosphatase 1 (MKP-1)--is a critical negative regulator of the myriad pro-inflammatory pathways activated by MAPKs in the airway. EXPERIMENTAL APPROACH(More)
The tyrosine kinase inhibitor drug sorafenib is used in the treatment of liver and renal cancers but adverse effects may necessitate dose interruption and under-dosage may lead to therapeutic failure. Sorafenib also undergoes cytochrome P450 (CYP)-dependent biotransformation to the N-oxide and other metabolites. However, although CYPs are major determinants(More)
BACKGROUND AND PURPOSE Imatinib is a clinically important inhibitor of tyrosine kinases that are dysregulated in chronic myelogenous leukaemia and gastrointestinal stromal tumours. Inter-individual variation in imatinib pharmacokinetics is extensive, and influences drug safety and efficacy. Hepatic cytochrome P450 (CYP) 3A4 has been implicated in imatinib(More)
The objective of this study was to determine crop and tree productivity in several alley cropping planting patterns. The four- year study was conducted in western Oregon, United States and involved irrigated sweet corn (Zea mays) intercropped between hedgerows of red alder (Alnus rubra) and black locust (Robina pseudoacacia). Three alley cropping planting(More)
Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) plays an essential role in lipid and glucose homeostasis. It is recognized as the receptor of the thiazolidinediones-a synthetic class of anti-diabetic drugs-and is the target of many drug discovery efforts because of its role in disease states, such as type II diabetes mellitus. In this study,(More)
The effect of cholesterol removal by methyl-beta-cyclodextrin on the dipole potential, psi(d), of membrane vesicles composed of natural membrane lipids extracted from the kidney and brain of eight vertebrate species was investigated using the voltage-sensitive fluorescent probe di-8-ANEPPS. Cyclodextrin treatment reduced cholesterol levels by on average 80%(More)
Synthetic cannabinoid (SC) designer drugs featuring bioisosteric fluorine substitution are identified by forensic chemists and toxicologists with increasing frequency. Although terminal fluorination of N-pentyl indole SCs is sometimes known to improve cannabinoid type 1 (CB1) receptor binding affinity, little is known of the effects of fluorination on(More)
Design, synthesis, and in vitro bioevaluation of a new class of potential dual PPARalpha and gamma agonists discovered through a structure-driven design paradigm are described. The 7-hydroxy-benzopyran-4-one moiety (includes flavones, flavanones, and isoflavones) is the key pharmacophore of these novel molecules, exhibiting similarity to the core structure(More)
Predictive models of plant diversity have typically focused on either a landscape's capacity for richness (equilibrium models), or on the processes that regulate competitive exclusion, and thus allow species to coexist (nonequilibrium models). Here, we review the concepts and purposes of a hierarchical, multiscale model of the controls of plant diversity(More)
Di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone (Dp44mT) demonstrates potent anti-cancer activity. We previously demonstrated that 14C-Dp44mT enters and targets cells through a carrier/receptor-mediated uptake process. Despite structural similarity, 2-benzoylpyridine 4-ethyl-3-thiosemicarbazone (Bp4eT) and pyridoxal isonicotinoyl hydrazone (PIH) enter(More)