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INHIBITORS AND IMMUNOASSAY FOR SEPTIC SHOCK/DIC

Award Information
Agency: Department of Defense
Branch: Army
Contract: N/A
Agency Tracking Number: 9572
Amount: $49,760.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: N/A
Solicitation Number: N/A
Timeline
Solicitation Year: N/A
Award Year: 1989
Award Start Date (Proposal Award Date): N/A
Award End Date (Contract End Date): N/A
Small Business Information
11077 N Torrey Pines Rd
La Jolla, CA 92037
United States
DUNS: N/A
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 Dr Michael G Pepe
 (619) 455-7626
Business Contact
Phone: () -
Research Institution
N/A
Abstract

DISSEMINATED INTRAVASCULAR COAGULATION (DIC) IS AN UNDERLYING PTHOGENETIC MECHANISM IN CASES OF VIREMIA (INCLUDING DENGUE HEMMORHAGIC FEVER) AND SEPTICEMIA. THE DEVELOPMENT OF THERAPY AND DECISIVE DIAGNOSTIC TECHNIQUES TO MONITOR THE PROGRESS OF THERAPY ARE IMPORTANT FOR INDIVIDUALS WITH SEPTIC SHOCK DUE TO THERMAL INJURY OR BIOLOGICAL WARFARE WHERE INFECTIONS RESULT IN A HIGH MORBIDITY AND MORTALITY. WE PROPOSE TO DEVELOP NOVEL PEPIDYL CHLOROMETHYL KETONES (CMKS) OF THERAPEUTIC UTILITY TO INTERRUPT ONE OF THE FUNDAMENTAL PATHOGENETIC MECHANISMS IN SEVERE LIFE-THREATING DIC, SEPTIC SHOCK, THROMBOTIC AND RELATED COMPLICATIONS IN WHICH THE INTRAVASCULAR ACTIVATION OF COAGULATION PLAYS A SIGNIFICANT ROLE. IRREVERSIBLE INHIBITORS ARE PREDICTED TO BE OF THERAPEUTIC VALUE BASED ON THE SPECIFIC BINDING TO THE SERINE PROTEASE CATALYTIC SITE OF THE TISSUE FACTOR (TF):FACTOR VII/VIIA DELLURLAR INITIATING COMPLEX OF COAGULATION AND THE SUBSEQUENT IRREVERSIBLE INHIBITION THEREOF. IMMUNOASSAYS OF PEPTIDES RELEASED UPON ACTIVATION OF ZYMOGENS IN THE CLOTTING CASCADE PROVIDE QUANTITATION AND ARE USEFUL DIAGNOSTIC INDICATORS OF ENZYMATIC ACTIVITY. THEREFORE, IN CONJUNCTION WITH A SPECIFIC INHIBITOR OF FACTOR VII/VIIA, WE ARE PROPOSING TO DEVELOP A SPECIFIC IMMUNOASSAY FOR FACTOR X ACTIVATION PEPTIDE WHICH WOULD MONITOR TF:FACTOR VII/VIIA ACTIVITY IN VITRO AND IN VIVO, FACILITATINGTHERAPEUTIC DECISION MAKING.

* Information listed above is at the time of submission. *

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