Risk of mortality from sepsis is complicated by infection-induced disseminated intravascular coagulopathy (DIC). To address a serious public health problem inadequately answered by currently licensed therapeutics is the aim of this investigation using botanicals to potentially suppress DIC in sepsis. Specifically, this research will investigate two effects, time to death and mean concentration of fibrinogen degradation products (FgnDP), a marker for DIC. It will compare control treatments versus botanical treatments in mice made septic with Escherichia coli. The three botanicals are selected because of their reputation in treating snakebite in Belize, a reputation previously validated in a murine model and supported by in vitro investigation of the mechanism of action. Now, new research will serve as background for an Investigational New Drug (IND) application where the indication for the drug is treatment of DIC in sepsis, which has a mechanism similar to DIC induced by venom. Innovation is demonstrated by 1) the cross-applicability of ethnobotanical research for snakebite to a mechanistically similar problem of wider public health concern 2) use of a novel assay to quantify FgnDP in mice to assess DIC and 3) pursuit of a new pathway for drug development for botanicals, only opened since 2004. Should success continue as it has for preclinical research with snake venom, one or all of these botanicals will be commercialized as drugs by 2015. A separate SBIR application is being submitted to ascertain botanical quality, batch- to- batch consistency and characterization and possibly, isolation of active ingredients.
Public Health Relevance: Infection can overwhelm the body and can cause severe bleeding/clotting. This is a common and serious health problem, but the currently marketed drug is inadequate for most patients. Proposed is investigation of promising botanical drugs.
Public Health Relevance: This Public Health Relevance is not available.
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