2, 76.1 and 207.7, respectively. The scavenging properties of cocoa powder against the superoxide anion, H(2)O(2), HClO, and peroxynitrite were also determined. The lCso (mu g/mL) values in the hypoxanthine/xanthine oxidase test were 77.5, 12.3 and 10.3, for A, B and C, respectively, while as an HOCl scavenger the IC(50) (mu g/mL)

values were 225.4, 73.2 and 21.5. As a peroxynitrite anion scavenger, only extract C had a relevant effect, with IC(50) (mu g/mL) values of 76.1 or 110.0 in the absence or presence of bicarbonate. None of the extracts tested showed activity in the hydrogen peroxide test, but B and C significantly increased the deoxyribose degradation in the absence of ascorbate. Likewise, none of the extracts inhibited KPT-8602 the ferrous or copper chelating activity at 100 mu g/mL, but they inhibited the lipid peroxidation in brain homogenates and human plasma through non-enzymatic

generation systems, with extract C giving the best IC(50) (mu g/mL) values: 17.4 and 8.1 against lipid peroxidation in brain homogenates and human plasma, respectively. In conclusion, if the extractive protocol is well characterized, defined and optimized, cocoa could constitute a source of polyphenols for enriching foods, nutraceuticals and alimentary supplements. (C) 2010 Elsevier Ltd. All rights reserved.”
“Background-

Brugada syndrome (BrS) is an arrhythmogenic disorder that has been linked to mutations in SCN5A, the gene encoding for the pore-forming alpha-subunit of the cardiac sodium channel. Typically, BrS mutations in SCN5A result in a reduction of sodium current with some mutations even exhibiting a dominant-negative selleck screening library effect on wild-type (WT) channels, thus leading to an even more prominent decrease in current amplitudes. However, there is also a category of apparently benign (atypical) BrS SCN5A mutations that in vitro demonstrates only minor biophysical defects. It is therefore not clear how these mutations produce a BrS phenotype. We hypothesized Fosbretabulin purchase that similar to dominant-negative

mutations, atypical mutations could lead to a reduction in sodium currents when coexpressed with WT to mimic the heterozygous patient genotype.

Methods and Results-

WT and atypical BrS mutations were coexpressed in Human Embryonic Kidney-293 cells, showing a reduction in sodium current densities similar to typical BrS mutations. Importantly, this reduction in sodium current was also seen when the atypical mutations were expressed in rat or human cardiomyocytes. This decrease in current density was the result of reduced surface expression of both mutant and WT channels.

Conclusions-

Taken together, we have shown how apparently benign SCN5A BrS mutations can lead to the ECG abnormalities seen in patients with BrS through an induced defect that is only present when the mutations are coexpressed with WT channels. Our work has implications for risk management and stratification for some SCN5A-implicated BrS patients.