Studies on Alternating Current Electrolysis. IV . Mathematical Treatment of Reversible Electron Transfer with Alternating Voltage Control and Distorted Current

A mathematical treatment is developed which yields equations relating faradaic current, voltage, and time when an alternating voltage is applied to an electrolytic cell composed of a plane and auxiliary electrodes immersed in a solution containing initially supporting electrolyte and only reversibly oxidizable or reducible species. Both oxidant and reductant are taken to be soluble, and specific adsorption is assumed to be absent. The voltage across that branch of the equivalent circuit through which only faradaic current flows is assumed to be periodic with fixed amplitude and with or without an additional direct applied voltage component; the resultant current is distorted. Diffusion controlled kinetics is postulated, and it is assumed that equilibrium is essentially established at the electrode surface. The equations developed show that a “steady state” (i.e., a periodic state) is quickly attained, yield diagnostic tests of use in establishing the reversible mechanism, make it possible to determine the standard potential, and finally yield for the periodic state a relation between faradaic current and time. These results are then generalized so as to include systems in which the reversible electrochemical step is followed by a sufficiently slow secondary reaction step. One diagnostic result of interest in the latter connection is that the mean faradaic current vanishes in the periodic state, regardless of the amplitude or of the shape of the applied periodic potential, when the follow‐up reaction occurs to a negligible extent

Hyperantithrombotic, noncytoprotective Glu149Ala-activated protein C mutant

Activated protein C (APC) reduces mortality in severe sepsis patients. APC exerts anticoagulant activities via inactivation of factors Va and VIIIa and cytoprotective activities via endothelial protein C receptor and protease-activated receptor-1. APC mutants with selectively altered and opposite activity profiles, that is, greatly reduced anticoagulant activity or greatly reduced cytoprotective activities, are compared here. Glu149Ala-APC exhibited enhanced in vitro anticoagulant and in vivo antithrombotic activity, but greatly diminished in vitro cytoprotective effects and in vivo reduction of endotoxin-induced murine mortality. Thus, residue Glu149 and the C-terminal region of APC's light chain are identified as functionally important for expression of multiple APC activities. In contrast to Glu149Ala-APC, 5A-APC (Lys191-193Ala + Arg229/230Ala) with protease domain mutations lacked in vivo antithrombotic activity, although it was potent in reducing endotoxin-induced mortality, as previously shown. These data imply that APC molecular species with potent antithrombotic activity, but without robust cytoprotective activity, are not sufficient to reduce mortality in endotoxemia, emphasizing the need for APC's cytoprotective actions, but not anticoagulant actions, to reduce endotoxin-induced mortality. Protein engineering can provide APC mutants that permit definitive mechanism of action studies for APC's multiple activities, and may also provide safer and more effective second-generation APC mutants with reduced bleeding risk