| Aspirin's ability to prevent blood coagulation has been cited since the 19th century. Contemporary research has focused on aspirin's antiplatelet actions to explain the anticoagulant effects. However, the reported similarities between salicylates and 4-hydroxycoumarin anticoagulants prompted this research. The hypothesis guiding this work is that aspirin is converted in vivo to 4-hydroxycoumarin, a known anticoagulant that inhibits vitamin K oxide reductase. ASA-Mal-CoA, a rationally designed and possible in vivo metabolite of aspirin, was incubated with extracts of an enteric bacterium, M. luteus, and was shown to produce 4-hydroxycoumarin. In vivo studies in rats connecting oral consumption of aspirin with inhibition of vitamin K oxide reductase further support this novel hypothesis.;Saxitoxin and tetrodotoxin, poisons isolated from shellfish and puffer fish, exert their toxic effects by inhibiting sodium influx into neurons. The current hypothesis on the mechanism of action of saxitoxin and tetrodotoxin is that these compounds bind to, and sterically block the entrance of the sodium channels, thus preventing sodium influx. A new hypothesis, that the toxins act on bNOS, a regulatory enzyme which controls sodium channel opening, has been asserted in this thesis. This research shows that saxitoxin inhibits bNOS at low micromolar concentrations. |
