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Inhibition of cardiac late sodium current (late I Na ) is a strategy to suppress arrhythmias and sodium-dependent calcium overload associated with myocardial ischemia and heart failure. Current inhibitors of late I Na are unselective and can be proarrhythmic. This study introduces GS967 (6-[4-(trifluoromethoxy), a potent and selective inhibitor of late I Na , and demonstrates its effectiveness to suppress ventricular arrhythmias. The effects of GS967 on rabbit ventricular myocyte ion channel currents and action potentials were determined. Anti-arrhythmic actions of GS967 were characterized in ex vivo and in vivo rabbit models of reduced repolarization reserve and ischemia. GS967 inhibited Anemonia sulcata toxin II (ATX-II)-induced late I Na in ventricular myocytes and isolated hearts with IC 50 values of 0.13 and 0.21 mM, respectively. Reduction of peak I Na by GS967 was minimal at a holding potential of 2120 mV but increased at 280 mV. GS967 did not prolong action potential duration or the QRS interval. GS967 prevented and reversed proarrhythmic effects (afterdepolarizations and torsades de pointes) of the late I Na enhancer ATX-II and the I Kr inhibitor E-4031 in isolated ventricular myocytes and hearts. GS967 significantly attenuated the proarrhythmic effects of methoxamine1clofilium and suppressed ischemiainduced arrhythmias. GS967 was more potent and effective to reduce late I Na and arrhythmias than either flecainide or ranolazine. Results of all studies and assays of binding and activity of GS967 at numerous receptors, transporters, and enzymes indicated that GS967 selectively inhibited late I Na . In summary, GS967 selectively suppressed late I Na and prevented and/or reduced the incidence of experimentally induced arrhythmias in rabbit myocytes and hearts.

A fast, precise and selective diode array HPLC method is presented for the extraction and analysis of soy isoflavonoids from foods and from human urine, plasma, and breast milk in support of mechanistic and epidemiologic studies assessing the potential cancer protective role of soya or isoflavones. Solid phase or solvent extraction was chosen for isolation, and enzymatic or acid hydrolysis procedures were used for aglycone production depending on the matrix to be analyzed. C-18 reversed-phase HPLC was applied to selectively separate and quantitate daidzein (1), glycitein (3), and genistein (4), including their malonyl (a) and acetyl (b) esters, and their mammalian metabolites equol (6) and O-desmethylangolensin (7), as well as formononetin (2), biochanin-A (5), and coumestrol (8) using a gradient elution system. UV absorbance scans and authentic standards were applied for identification purposes, additional to fluorometric monitoring, electrochemical detection, and GC/ MS analysis after trimethyl silylation. Detection limits of 20-microl injections were found to be 1.09, 0.53, 3.28, and 1.00 pmoles for daidzein, genistein, equol, and O-desmethylangolensin (DMA), respectively, by monitoring at the individual compound's absorption maximum. The proposed method was applied to monitor isoflavone levels in soy foods and in human plasma, urine and breast milk after challenge with roasted soybeans. Implications of the presented results on the potential activity of isoflavones to prevent cancer by exposing newborn infants to these agents are discussed.

11Purple-fleshed sweet potato P40 has been shown to prevent colorectal cancer in a murine 12 model. This study is to identify anthocyanins by using HPLC/MS-MS and assess the stability 13 during various cooking conditions. P40 possesses a high content of anthocyanins up to 14 mg/g 14 dry matter. Total 12 acylated anthocyanins are identified. Top three anthocyanins, e.g., cyanidin 15 3-caffeoyl-p-hydroxybenzoyl sophoroside-5-glucoside, peonidin 3-caffeoyl sophoroside-5-16 glucoside, and cyanidin 3-(6'' -caffeoyl-6''-feruloylsophoroside)-5-glucoside, account for half 17 of the anthocyanin contents. Over 80% of anthocyanins measured by acid hydrolysis were 18 cyanidin derivatives, indicating P40 is unique when compared with other purple-fleshed sweet 19 potatoes that usually contain more peonidin than cyanidin. Steaming, pressure cooking, 20 microwaving, and frying but not baking significantly reduced 8-16% of total anthocyanin 21 contents. Mono-acylated anthocyanins showed a higher resistance against heat than di-and non-22 acylated. Among of which, cyanidin 3-p-hydroxybenzoylsophoroside-5-glucoside exhibited the 23 best thermal stability. The stable acylated and cyanidin-predominated anthocyanins in P40 may 24 provide extra benefits for cancer prevention. 25Keywords: Anthocyanins / purple-fleshed sweet potato / cancer prevention / stability / cooking 26 conditions 27

Fruit and vegetable intake is inversely correlated with risks for several chronic diseases in humans. Phytochemicals, and in particular, phenolic compounds, present in plant foods may be partly responsible for these health benefits through a variety of mechanisms. Since environmental factors play a role in a plant's production of secondary metabolites, it was hypothesized that an organic agricultural production system would increase phenolic levels. Cultivars of leaf lettuce, collards, and pac choi were grown either on organically certified plots or on adjacent conventional plots. Nine prominent phenolic agents were quantified by HPLC, including phenolic acids (e. g. caffeic acid and gallic acid) and aglycone or glycoside flavonoids (e. g. apigenin, kaempferol, luteolin, and quercetin). Statistically, we did not find significant higher levels of phenolic agents in lettuce and collard samples grown organically. The total phenolic content of organic pac choi samples as measured by the Folin-Ciocalteu assay, however, was significantly higher than conventional samples (p < 0.01), and seemed to be associated with a greater attack the plants in organic plots by flea beetles. These results indicated that although organic production method alone did not enhance biosynthesis of phytochemicals in lettuce and collards, the organic system provided an increased opportunity for insect attack, resulting in a higher level of total phenolic agents in pac choi.