Current Highlight from December 4, 2015
Human Infant Intestinal Microbiota as a Reservoir of Antimicrobial Resistance
Studies of the microbiota of mothers and their infants by collaborators at NCTR, the Norwegian University of Life Sciences, and the University of Reading in the UK, demonstrated that intestinal microbiota could serve as a reservoir of antimicrobial resistance genes. This suggests the careful selection of antibiotics an important consideration for the treatment of infections. High-throughput sequence analyses indicated a 15% prevalence of integrons in the study population of 147 mothers and their infants, which were typically associated with antimicrobial resistance genes. These integrons were likely carried on potentially transmissible plasmids and were more stable than the overall bacterial populations. This may explain why the integrons persisted, even though there were changes in the bacterial population structure.
For additional information, please contact Steven Foley, Ph.D., Division of Microbiology, FDA/NCTR; or refer toNature’s Scientific Reports.
PBPK Model for Assessment of Human Exposure to Bisphenol A
Collaborators at NCTR and Pacific Northwest National Laboratory modified and recalibrated a nonhuman primate, PBPK model for Bisphenol A (BPA), by incorporating human data to reduce uncertainties associated with the model simulations. The new model incorporated experimental data (serum concentration and urinary excretion profiles) from human volunteers who consumed deuterated (d6) BPA added in cookies and soup; along with in vitro studies on BPA metabolism in the liver and the small intestine. This model improves human-exposure assessments and reduces uncertainties incurred during extrapolation across doses and species. A manuscript describing the model is available online at Toxicology and Applied Pharmacology.
For additional information, please contact Jeffrey Fisher, Ph.D., or Xiaoxia Yang, Staff Fellow, Division of Biochemical Toxicology, FDA/NCTR.
Extracellular microRNAs (miRNAs) as Clinical Biomarkers for Drug-Induced Toxicity
NCTR scientists published a review article in Biomarkers in Medicine. The review article provides an overview of miRNA turnover, stability, and release in body fluids; a discussion of current analytical technologies for the quantification of miRNA; and examples of nonclinical and clinical studies addressing the use of extracellular miRNAs as biomarkers of drug-induced heart, liver, and kidney toxicity. Currently, a lack of standardization and concerns about the comparability of results from multiple analytical platforms has slowed the development of miRNAs as clinical biomarkers. Thus, validation of candidate miRNAs in larger studies and the development of quantitative methods to measure low miRNA concentrations in body fluids is proposed.
For additional information, please contact Xi Yang, Ph.D., Visiting Scientist, Division of Systems Biology, FDA/NCTR.
NCTR Research Highlights Archives
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