University of Arkansas for Medical Sciences

About: University of Arkansas for Medical Sciences is a education organization based out in Little Rock, Arkansas, United States. It is known for research contribution in the topics: Population & Health care. The organization has 14077 authors who have published 26012 publications receiving 973592 citations. The organization is also known as: UAMS.

Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans.

Abstract: Objectives Phytochemical-mediated modulation of cytochrome P450 (CYP) activity may underlie many herb-drug interactions. Single-time point phenotypic metabolic ratios were used to determine whether long-term supplementation of St John's wort, garlic oil, Panax ginseng, and Ginkgo biloba affected CYP1A2, CYP2D6, CYP2E1, or CYP3A4 activity. Methods Twelve healthy volunteers (6 females) were randomly assigned to receive either St John's wort, garlic oil, P ginseng, or G biloba for 28 days. For each subject, a 30-day washout period was interposed between each supplementation phase. Probe-drug cocktails of midazolam, caffeine, chlorzoxazone, and debrisoquin (INN, debrisoquine) were administered before supplementation (baseline) and at the end of supplementation. Presupplementation and postsupplementation phenotypic trait measurements were determined for CYP3A4, CYP1A2, CYP2E1, and CYP2D6 with the use of 1-hydroxymidazolam/midazolam serum ratios (1-hour sample), paraxanthine/caffeine serum ratios (6-hour sample), 6-hydroxychlorzoxazone/chlorzoxazone serum ratios (2-hour sample), and debrisoquin urinary recovery ratios (8-hour collection), respectively. Results Comparisons of presupplementation and postsupplementation ratios indicated that St John's wort significantly induced the activity of CYP2E1 and CYP3A4 (P < .0001). Among female subjects, St John's wort produced significantly greater increases in CYP3A4 phenotypic ratios that appeared to be unrelated to body mass index. This finding is suggestive of a sexual dimorphism in CYP3A4 inducibility. Garlic oil reduced CYP2E1 activity by 39% (P = .030), whereas no significant effect on CYP activity was observed for P ginseng and G biloba. Conclusions Single-time point phenotypic metabolic ratios may provide a practical means of predicting CYP-mediated herb-drug interactions in humans. Clinical Pharmacology & Therapeutics (2002) 72, 276–287; doi: 10.1067/mcp.2002.126913

An electrophysiological investigation of semantic priming with pictures of real objects.

Abstract: Event-related potentials were recorded using color pictures of real objects. Participants made relatedness judgments for pictures that were highly, moderately, or unrelated to a picture of a preceding prime object (Experiment 1) or object identification decisions for related/easily identified, unrelated/easily identified, and unrelated/unidentifiable objects preceded by prime objects (Experiment 2). Unrelated pictures elicited larger event-related potential negativities between 225 and 500 ms than did related pictures, although the first portion of this epoch had a more frontal distribution than did the later portion. The later epoch differentiated the unrelated from the moderately related and the moderately related from the highly related pictures (Experiment 1), but the early epoch produced differences only between the unrelated and related pictures (Experiments 1 and 2). This pattern supports the existence of two separate components, an anterior, image-specific N300 and a later, central/parietal amodal N400.

Reactive oxygen and mechanisms of inflammatory liver injury

Abstract: Reactive oxygen species (ROS) are important cytotoxic and signalling mediators in the pathophysiology of inflammatory liver diseases. They can be generated by resident and infiltrating phagocytes and/or intracellularly in every liver cell type after stimulation with cytokines. Although ROS are able to cause cell destruction by massive lipid peroxidation, in most cases, ROS are more likely to modulate signal transduction pathways by affecting redox-sensitive enzymes, organelles (e.g. mitochondria) and transcription factors. Thus, ROS can directly induce and/or regulate apoptotic and necrotic cell death. In addition, ROS can have indirect effects on the pathophysiology by supporting protease activity through inactivation of antiproteases and by modulating the formation of inflammatory mediators and adhesion molecules. Many of the effects of ROS may occur simultaneously or sequentially in the pathophysiology. Although mainly described in this review as detrimental, ROS are essential for host-defence functions of phagocytes and can modulate the formation of mediators involved in regulating sinusoidal blood flow and liver regeneration. Thus, continuous efforts are necessary to improve our understanding of the role of ROS in the pathophysiology of inflammatory liver diseases and to discover therapeutic interventions that selectively target the negative effects of reactive oxygen formation.