Methods and Results: Flecainide prevented catecholamine-induced sustained ventricular tachycardia in RyR2R4496C؉/؊ mice. Cellular studies were performed with isolated RyR2 R4496C؉/؊ myocytes. Isoproterenol caused the appearance of spontaneous Ca 2؉ transients, which were unaffected by flecainide (6 mol/L). Flecainide did not affect Ca 2؉ transient amplitude, decay, or sarcoplasmic reticulum Ca 2؉ content. Moreover, it did not affect the frequency of spontaneous Ca 2؉ sparks in permeabilized myocytes. In contrast, flecainide effectively prevented triggered activity induced by isoproterenol. The threshold for action potential induction was increased significantly (P<0.01), which suggests a primary extracellular antiarrhythmic effect mediated by Na ؉ channel blockade. Conclusions: Flecainide prevents catecholaminergic polymorphic ventricular tachycardia in RyR2R4496C؉/؊ mice; however, at variance with previous reports, we observed minimal effects on intracellular Ca 2؉ homeostasis. Our data suggest that the antiarrhythmic activity of the drug is caused by reduction of Na

These observations do not support the view that PFOA and PFOS are actively concentrated in the thyroid. PFOA and PFOS, however, are both found in surgical and autopsy thyroid specimens. Therefore, further studies to determine if they have disrupting effects in thyroid cells or tissue, and studies to compare populations with and without these compounds in their thyroid glands, are important.

In this work, an ultra-performance liquid chromatography electrospray ionization (UPLC-ESI)-MS/MS methodology based on multiple reaction monitoring (MRM) for the selective and sensitive detection and quantification of durum wheat adulteration has been developed and fully validated. The targeted analysis was performed by monitoring specific transitions at m/z 543.7 > 657.4 and m/z 543.7 > 299.2 of a species-specific marker derived from a tryptic peptide of puroindoline a (Pin-a), a cysteine-rich protein selectively present only in common wheat. In addition, two transitions at m/z 500.4 > 725.4 and m/z 500.4 > 561.9 of a reference peptide belonging to purothionin A-1, present in both species, were also monitored. The calibration curves obtained on binary mixtures with known percentages of common/durum wheat flours showed linearity (coefficient of regression, r ≥ 0.99) over concentrations that ranged between 80 and 1%. The limit of detection (LOD) and limit of quantification (LOQ) for the Pin-a marker in wheat flours were 0.01 and 0.03%, respectively. The identified Pin-a marker was also found to be highly diagnostic for the quantification of common wheat in raw materials (kernels) and processed products (pasta), thus offering new opportunities to assess food authenticity.