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Professor; Pharmacology; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: (adapted from applicant's abstract): Phosphoenol pyruvate (PEP) is a highly functionalized, chemically versatile molecule involved at several intersections of cellular energy metabolism and biosynthesis. While most enzymatic reactions utilizing PEP as a substrate involve cleavage of the high energy P-O, two types of reactions have been shown to involve the unusual cleavage of the C-O bond of PEP.
After postoperative stabilization in a tether, we will; (1) inoculate Group B Streptococci (GBS) into the amniotic fluid to establish intrauterine infection and preterm labor. Uterine contractility will be continuously Studies 29 monitored and periodic samples of amniotic fluid and maternal and fetal blood (1-4 cc) will be obtained for assays of eicosanoids, steroid hormones, cytokines, matrix metalloproteinases and for microbial studies; (2) utilize antibiotics with and without potent inhibitors of proinflammatory cytokine production (dexamethasone,IL-10) o prostaglandin production (indomethacin) to ascertain the most effective intervention to down-regulate the cytokine/prostaglandin cascade and associated uterine activity; (3) infuse proinflammatory cytokine IL-1beta into the amniotic cavity through indwelling catheters in the absence of infection.
Professor; Medicinal Chemistry; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2001; Project Start 01-JUL-1996; Project End 31-MAR-2005 Summary: (Provided by Applicant) Health care providers are challenged daily by an increasing resistance of pathogenic bacteria to their antibacterial arsenal. To overcome this problem, it is necessary to design new and innovative antibiotics with totally different modes of action so that, no cross-resistance with present agents should occur.
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