Abstract: Methods for the treatment of sepsis with complement inhibitors are disclosed. In particular, C3 inhibitors, such as Compstatin and Compstatin analogs, are administered at various times following the onset of sepsis to alleviate tissue damage and organ failure, which are hallmarks of the second, extravascular stage of sepsis. Combination therapies for comprehensive treatment of sepsis are also disclosed. Pharmaceutical compositions and kits for use in the methods are disclosed as well.

Abstract: Methods for the treatment of sepsis with complement inhibitors are disclosed. In particular, C3 inhibitors, such as Compstatin and Compstatin analogs, are administered at various times following the onset of sepsis to alleviate tissue damage and organ failure, which are hallmarks of the second, extravascular stage of sepsis. Combination therapies for comprehensive treatment of sepsis are also disclosed. Pharmaceutical compositions and kits for use in the methods are disclosed as well.

Abstract: A method for inhibiting and for reversing the dysfunctional response of vascular endothelial cells to an inflammatory stimulus in a subject in need of such therapy has been developed in which an effective amount of a pharmaceutical composition comprising thrombin-activatable fibrinolysis inhibitor (TAFI) combined with a pharmaceutically acceptable carrier and optionally other treatments is administered to the subject.

Abstract: A method for inhibiting and for reversing the dysfunctional response of vascular endothelial cells to an inflammatory stimulus in a subject in need of such therapy has been developed in which an effective amount of a pharmaceutical composition comprising thrombin-activatable fibrinolysis inhibitor (TAFI) combined with a pharmaceutically acceptable carrier and optionally other treatments is administered to the subject.

Abstract: It has been discovered that the dysfunction of microvascular endothelium associated with microvascular thrombosis associated with diabetes mellitus can be treated by infusion of activated Protein C. As demonstrated by the example, infusion of an insulin-dependent baboon and normal baboons demonstrated that one can normalize the thrombin-antithrombin (TAT), activated protein C/protein C inhibitor (APC/PCI) and protein C( PC).

Abstract: An anticoagulant composition containing an effective amount of factor Xa having the active serine site inactivated that functions rapidly and effectively in vivo to suppress coagulation. In a preferred embodiment, Factor Xa, a serine esterase that forms a complex with Factor Va, Ca++, and phospholipid to catalyze prothrombin activation, is first inactivated with an active site inhibitor, such as dansyl-glu- gly-arg-chloromethyl ketone, to form inactivated factor Xa. In another embodiment, Factor Xa is expressed from a gene sequence wherein the portion encoding the active serine region is modified. The inactivated protein retains the ability to bind to endogenous factor Va in vivo, and has a half-life of approximately ten hours. Administration of inactive factor Xa to the blood of a patient results in the formation of inactive factor Xa-Va complexes in vivo, thereby inhibiting coagulation.

Abstract: A pharmaceutical composition comprising activated protein C activity is used to treat subjects for permeability and coagulopathic dysfunctions of vascular endothelial cells in response to an inflammatory stimulus. The composition may be used to prevent or to reverse these pathological events. Further, the composition is used to prevent elevated plasma levels of tumor necrosis factor, an inflammatory mediator which participates in the chain of events which produce the dysfunctional responses.