Christine N. Galinski

Revisiting the mechanistic basis of the French Paradox: Red wine inhibits the activity of protein disulfide isomerase in vitro.

INTRODUCTION Although epidemiologic evidence points to cardioprotective activity of red wine, the mechanistic basis for antithrombotic activity has not been established. Quercetin and related flavonoids are present in high concentrations in red but not white wine. Quercetin-glycosides were recently shown to prevent thrombosis in animal models through the inhibition of extracellular protein disulfide isomerase (PDI). We evaluated whether red or white wine inhibited PDI activity in vitro. METHODS Quercetin levels in red and white wines were measured by HPLC analysis. Inhibition of PDI activity by red and white wines was assessed by an insulin reduction turbidity assay at various concentrations of wine. PDI inhibition was confirmed using a reduced peptide that contained a disulfide containing peptide as a substrate. The inhibition of PDI related thiol isomerases ERp5 and ERp57 was also assessed. RESULTS We observed a dose-dependent decrease of PDI activity for a variety of red but not white wines. Red wine diluted to 3% final concentration resulted in over 80% inhibition of PDI activity by insulin reductase assay for all varieties tested. This inhibition was also observed in the peptide based assay. Red grape juice yielded similar results but ethanol alone did not affect PDI activity. Interestingly, red wine also inhibited the PDI related thiol isomerases ERp5 and ERp57, albeit to a lesser degree than PDI. CONCLUSIONS PDI activity is inhibited by red wine and grape juice, identifying a potentially novel mechanism underlying the cardiovascular benefits attributed to wine consumption.

Comparison of Introductory Pharmacy Practice Experiences Among US Pharmacy Programs

Objective. To identify the various IPPE designs utilized by US pharmacy programs. Methods. A 20-question survey was developed and distributed to experiential affairs professionals at 129 pharmacy institutions nationwide addressing school demographics and IPPE design. Results were analyzed in aggregate. Results. Ninety-three schools responded (72%). Eighty-nine percent of those reported beginning IPPE experiences in the first professional year, although there was a great variation regarding whether the IPPE was held while didactic classes were in session or during school breaks. The number of required practice experiences varied. Institutions prohibited students from completing rotations in the same pharmacy chain (72%) or hospital (70%) where employed, and from completing 2 rotations at the same site (62%). Fifty-seven percent utilized faculty members as preceptors. 51% allowed a maximum of 2 students per preceptor per practice experience. Conclusion. While clear trends existed in IPPE curricula, institutions incorporated aspects that addressed unique needs. Further research can determine the benefits and drawbacks of different IPPE designs.