An analytical comparison between point-of-care uric acid testing meters.

OBJECTIVE: A key goal in gout treatment is achieving sustained serum uric acid (sUA) lowering. Point-of-care test (PoCT) meters provide convenient, rapid measures of sUA levels to monitor/adjust therapy. Four commercially available sUA PoCT meters were compared qualitatively (ease of use) and quantitatively (precision/accuracy). METHODS: Liquid chromatography mass spectrometry (LC-MS) analysis was used as a laboratory reference method to compare precision of PoCT devices using blood samples from 20 healthy volunteers. Accuracy was compared against the LC-MS reference method and a laboratory clinical chemistry platform. RESULTS: Qualitatively, EasyTouch(®) GU and UASure were least user-friendly, requiring repeated attempts for accurate use. HumaSens and BeneCheck provided good usability and assay precision. Cross-validation of meter precision with laboratory-based uricase assay gave good correlations between both methods (R(2) = 0.8061 and 0.7605, respectively). CONCLUSION: UA PoCT meters can be important in managing gout, and the characteristics compared herein may enhance successful patient uptake.

HepaRG cells as human-relevant in vitro model to study the effects of inflammatory stimuli on cytochrome P450 isoenzymes.

The suppression of hepatic cytochrome P450 (P450) expression during inflammatory and infectious diseases and the relief of this suppression by successful disease treatment have been previously demonstrated to impact drug disposition. To address this clinically relevant phenomenon preclinically, the effect of proinflammatory cytokines on P450 isoenzymes in human hepatocytes has been examined by several researchers. In the present study we used the human hepatoma cell line (HepaRG) and cryopreserved primary human hepatocytes to investigate the effects of various inflammatory stimuli on P450 levels with the aim of further characterizing HepaRG cells as a useful surrogate for primary hepatocytes. In this study, HepaRG cells were exposed to bacterial lipopolysaccharide (LPS), interleukin-6 (IL-6), and interleukin-18 (IL-18) for 48 or 72 hours. The effects on CYP1A2, CYP2B6, and CYP3A4 mRNA and catalytic activity (phenacetin-O-deethylase, bupropion-hydroxylase, and midazolam-1'-hydroxylase) were measured. Cryopreserved pooled plateable hepatocytes were also exposed to IL-6 or IL-18 for 48 hours, and the effects on CYP1A2, CYP2B6, and CYP3A4 mRNA levels were measured. The exposure of HepaRG cells to IL-6 and LPS resulted in suppression of CYP1A2, CYP2B6, and CYP3A4 mRNA levels as well as their catalytic activities. However, no suppression of P450 activities or mRNA levels was observed after exposure to IL-18. Similar results on CYP1A2, CYP2B6, and CYP3A4 mRNA levels were observed with primary hepatocytes. The present study indicates that different proinflammatory mediators influence the expression of P450 differentially and that HepaRG cells may be used as an alternative to human hepatocytes for studies on cytokine-mediated suppression of drug-metabolizing enzymes.