The dietary flavonoid quercetin activates BKCa currents in coronary arteries via production of H2O2. Role in vasodilatation

OBJECTIVE: Large conductance Ca(2+)-activated K(+) channels (BKCa) regulate coronary artery tone in vivo, play a key role in blood pressure regulation, and have been suggested as novel potential drug targets in hypertension. Quercetin exerts systemic and coronary vasodilator effects in vitro and reduces blood pressure in several rat models of hypertension, and its consumption is associated with a lower mortality rate from coronary heart disease in epidemiological studies. We hypothesized that quercetin might activate BKCa channel in isolated myocytes from rat coronary arteries and that this mechanism might be involved in its coronary artery relaxant effects. METHODS: Membrane currents were measured using the whole-cell configuration of the patch-clamp technique. Contractile tension was recorded in rat coronary artery rings mounted in a myograph. RESULTS: Quercetin (>0.1 muM) increased the outward currents in the whole range of test potentials, hyperpolarized cell membranes, and increased the frequency of spontaneous transient outward currents (STOCs) carried by BKCa channels. These effects were abolished by the selective BKCa blocker iberiotoxin and by catalase. Quercetin increased dichlorofluorescein fluorescence in coronary arteries in a polyethylenglycol-catalase-sensitive manner, indicating that it increased cytosolic H(2)O(2). The membrane-permeable analogue of H(2)O(2)t-butylhydroperoxide mimicked the effects of quercetin on outward currents. The vasodilator effect of quercetin in isolated rat coronary arteries was partially inhibited by iberiotoxin. CONCLUSION: Quercetin increased BKCa currents via production of intracellular H(2)O(2). This effect is involved, at least partly, in the coronary vasodilator effects of quercetin.     

The alkaloid 4-methylaaptamine isolated from the sponge Aaptos aaptos impairs Herpes simplex virus type 1 penetration and immediate-early protein synthesis

We describe in this paper that the alkaloid 4-methylaaptamine, isolated from the marine sponge Aaptos aaptos, inhibited HSV-1 infection. We initially observed that 4-methylaaptamine inhibited HSV-1 replication in Vero cells in a dose-dependent manner with an EC50 value of 2.4 microM. Moreover, the concentration required to inhibit HSV-1 replication was not cytotoxic, since the CC50 value of 4-methylaaptamine was equal to 72 microM. Next, we found that 4-methylaaptamine sustained antiherpetic activity even when added to HSV-1-infected Vero cells at 4 h after infection, suggesting that this compound inhibits initial events during HSV-1 replication. We observed that 4-methylaaptamine impaired HSV-1 penetration without affecting viral adsorption. In addition, the tested compound could inhibit, in an MOI-dependent manner, the expression of an HSV-1 immediate-early protein, ICP27, thus preventing the inhibition of macromolecular synthesis induced by this virus. Our results warrant further investigation on the pharmacokinetics of 4-methylaaptamine and propose that this alkaloid could be considered as a potential compound for HSV-1 therapy.     

Study of the motion artefacts of skin-mounted inertial sensors under different attachment conditions

A common problem shared by accelerometers, inertial sensors and any motion measurement method based on skin-mounted sensors is the movement of the soft tissues covering the bones. The aim of this work is to propose a method for the validation of the attachment of skin-mounted sensors. A second-order (mass-spring-damper) model was proposed to characterize the behaviour of the soft tissue between the bone and the sensor. Three sets of experiments were performed. In the first one, different procedures to excite the system were evaluated to select an adequate excitation stimulus. In the second one, the selected stimulus was applied under varying attachment conditions while the third experiment was used to test the model. The heel drop was chosen as the excitation method because it showed lower variability and could discriminate between different attachment conditions. There was, in agreement with the model, a trend to increase the natural frequency of the system with decreasing accelerometer mass. An important result is the development of a standard procedure to test the bandwidth of skin-mounted inertial sensors, such as accelerometers mounted on the skin or markers heavier than a few grams.