The Cross-Border Biotech Blog

Biotechnology, Health and Business in Canada, the United States and Worldwide

Tag Archives: CYP450

Friday Science Review: December 31, 2010

Just a couple papers to squeeze in this year before the clock strikes 12. I look forward to 2011 and the research it will bring in the Canadian realm. For those readers heading out tonight for some fun on the city, enjoy! More science reviews to come in the new year..

Porcine Adenovirus PAV3, A Novel and Promising Candidate for H5N1 Protection

National Microbiology Laboratory, Winnipeg ♦ Published in PLoS ONE, Dec. 16, 2010

Researchers have provided evidence that suggests a porcine adenovirus, PAV3, has greater vaccine efficacy than the human adenovirus AdHu5 in protecting against H5N1. An avian influenza H5N1 mouse model was used to compare immune response and protection following vaccination with the two different vectors. Mice that were vaccinated with a replication defective PAV3 vector carrying an H5N1 antigen expressed higher concentrations of neutralizing antibody post-vaccination and had stronger cellular immune responses than mice vaccinated with AdHu5. After challenging vaccinated mice with H5N1 infection, Dr. Gary Kobinger and his team demonstrated that mice inoculated with PAV3 showed higher overall survival. Another notable finding was that the porcine adenovirus did not become significantly neutralized when exposed to a pool of antibodies generated from 10,000 humans.

Study of Human Heart Microsomes Gives Insight into Cardiac CYP450s

University of Montreal ♦ Published in PLoS ONE, Dec. 14, 2010

Enzymes from the cytochrome P450 (CYP450) superfamily play an important role in drug metabolism. Variation in CYP450 isoforms can lead to inter-subject and inter-organ variability in drug metabolism, thus their study is crucial to understanding the metabolism of specific drugs. Dr. Jacques Turgeon and his colleagues at the University of Montreal gathered data on CYP450 mRNA levels in left and right ventricular samples taken from the explanted hearts of patients with end-stage heart failure. Samples were processed in the lab to extract microsomes, small vesicle-like structures composed of endoplasmic reticulum that contain large quantities of CYP450s. Among the interesting findings of this body of work is that CYP2J2 was the most abundant isoform found in cardiac tissue samples. Levels of CYP450 mRNA were similar across ischemic and non-ischemic samples and between left and right ventricles. Another principal and interesting finding was that the stereoselectivity of cardiac CYP450s was reversed compared to those in the liver. After exposing heart microsomes to the calcium channel blocker verapamil, higher levels of CYP450-dependent metabolites were observed in the presence of the R-enantiomer.

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