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Cheng J.,Virginia Commonwealth University | Joyce A.,Venebio Group LLC | Aouizerat B.,University of California at San Francisco | Sanyal A.J.,Virginia Commonwealth University
PLoS ONE | Year: 2012

Vitamin E was recently shown to improve hepatic histology in a randomized controlled trial of pioglitazone or vitamin E for nonalcoholic steatohepatitis (PIVENS). The current study utilized samples collected in the PIVENS trial to identify: (1) baseline metabolomic profiles that could identify who would respond to vitamin E treatment and (2) end of treatment metabolomic profiles reflective of histologic improvement. A comprehensive analysis of metabolomics profiles (n = 547) quantified by mass spectrometry was performed in vitamin E responders (n = 16), vitamin E non-responders (n = 15), and placebo responders (n = 15). At baseline, phenyl-propionic acid (Odds ratio: 29.4, p<0.01), indole-propionic acid levels (Odds ratio: 16.2, p<0.01) were directly associated with a subsequent histologic response to vitamin E treatment whereas γ-carboxyethylhydroxychroman (CEHC) levels were inversely related to histologic response. Adjusting for baseline values by analysis of covariance, the end of treatment levels of gamma-glutamyl leucine (Fold change: 0.82, p<0.02) and gamma-glutamyl valine (Fold change: 0.8, p<0.03) were significantly lower in vitamin E responders compared to non-responders. The levels of gamma-glutamyl transpeptidase were not significantly different across the two groups. Subjects receiving placebo who demonstrated a histologic improvement also demonstrated lower levels of gamma-glutamylated amino acids (leucine, valine and isoleucine) compared to vitamin E non-responders. These data provide exploratory proof that there are measurable differences in the metabolic profile of subjects who are likely (vs unlikely) to respond to vitamin E treatment for NASH and in those experiencing histologic improvement (vs no improvement) on treatment and support further studies to validate these biomarkers. © 2012 Cheng et al.

Lavonas E.J.,Rocky Mountain Poison and Drug Center | Severtson S.G.,Rocky Mountain Poison and Drug Center | Martinez E.M.,Rocky Mountain Poison and Drug Center | Bucher-Bartelson B.,Rocky Mountain Poison and Drug Center | And 8 more authors.
Journal of Substance Abuse Treatment | Year: 2014

Buprenorphine abuse is common worldwide. Rates of abuse and diversion of three sublingual buprenorphine formulations (single ingredient tablets; naloxone combination tablets and film) were compared. Data were obtained from the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS®) System Poison Center, Drug Diversion, Opioid Treatment (OTP), Survey of Key Informants' Patients (SKIP), and College Survey Programs through December 2012. To control for drug availability, event ratios (rates) were calculated quarterly, based on the number of patients filling prescriptions for each formulation ("unique recipients of a dispensed drug," URDD) and averaged and compared using negative binomial regression. Abuse rates in the OTP, SKIP, and College Survey Programs were greatest for single ingredient tablets, and abuse rates in the Poison Center Program and illicit diversion rates were greatest for the combination tablets. Combination film rates were significantly less than rates for either tablet formulation in all programs. No geographic pattern could be discerned. © 2014 The Authors.

Puri P.,Virginia Commonwealth University | Xu J.,University of Southern California | Vihervaara T.,Zora Biosciences Oy Espoo | Katainen R.,Zora Biosciences Oy Espoo | And 7 more authors.
Journal of Lipid Research | Year: 2016

Alcohol- and obesity-related liver diseases often coexist. The hepatic lipidomics due to alcohol and obesity interaction is unknown. We characterized the hepatic lipidome due to 1) alcohol consumption in lean and obese mice and 2) obesity and alcohol interactions. In the French-Tsukamoto mouse model, intragastric alcohol or isocaloric dextrose were fed with either chow (lean) or high-fat, highcholesterol diet (obese). Four groups (lean, lean alcohol, obese, and obese alcohol) were studied. MS was performed for hepatic lipidomics, and data were analyzed. Alcohol significantly increased hepatic cholesteryl esters and diacylglycerol in lean and obese but was more pronounced in obese. Alcohol produced contrasting changes in hepatic phospholipids with significant enrichment in lean mice versus significant decrease in obese mice, except phosphatidylglycerol, which was increased in both lean and obese alcohol groups. Most lysophospholipids were increased in lean alcohol and obese mice without alcohol use only. Prostaglandin E2; 5-, 8-, and 11-hydroxyeicosatetraenoic acids; and 9- and 13-hydroxyoctadecadienoic acids were considerably increased in obese mice with alcohol use. Alcohol consumption produced distinct changes in lean and obese with profound effects of obesity and alcohol interaction on proinflammatory and oxidative stress-related eicosanoids. © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

Edmiston J.S.,Altria Client Services Inc. | Archer K.J.,Virginia Commonwealth University | Archer K.J.,StatSolvers LLC | Scian M.J.,Altria Client Services Inc. | And 3 more authors.
Biomarkers | Year: 2010

Background: Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease with associated systemic effects. Objective: To use gene expression microarrays in peripheral blood leukocytes of current and former cigarette smokers to identify differences associated with COPD. Materials and methods: Random forest modelling and a split-sample casecontrol approach were used to identify candidate predictors. Results: We identified 1013 genes and one smoking exposure variable that differentiated current and former smokers with or without COPD. This predictor set was reduced to a nine-gene classifier (IL6R, CCR2, PPP2CB, RASSF2, WTAP, DNTTIP2, GDAP1, LIPE and RPL14). Conclusion: These gene expression profiles represent potential biomarkers for COPD and may help increase mechanistic understanding of the disease. © 2010 Informa UK, Ltd.

McClay J.L.,Virginia Commonwealth University | Adkins D.E.,Virginia Commonwealth University | Isern N.G.,Pacific Northwest National Laboratory | O'Connell T.M.,University of North Carolina at Chapel Hill | And 10 more authors.
Journal of Proteome Research | Year: 2010

Chronic obstructive pulmonary disease (COPD), characterized by chronic airflow limitation, is a serious public health concern. In this study, we used proton nuclear magnetic resonance (1H NMR) spectroscopy to identify and quantify metabolites associated with lung function in COPD. Plasma and urine were collected from 197 adults with COPD and from 195 without COPD. Samples were assayed using a 600 MHz NMR spectrometer, and the resulting spectra were analyzed against quantitative spirometric measures of lung function. After correcting for false discoveries and adjusting for covariates (sex, age, smoking) several spectral regions in urine were found to be significantly associated with baseline lung function. These regions correspond to the metabolites trigonelline, hippurate and formate. Concentrations of each metabolite, standardized to urinary creatinine, were associated with baseline lung function (minimum p-value) 0.0002 for trigonelline). No significant associations were found with plasma metabolites. Urinary hippurate and formate are often related to gut microflora. This could suggest that the microbiome varies between individuals with different lung function. Alternatively, the associated metabolites may reflect lifestyle differences affecting overall health. Our results will require replication and validation, but demonstrate the utility of NMR metabolomics as a screening tool for identifying novel biomarkers of pulmonary outcomes. © 2010 American Chemical Society.

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