Novel thiazole-based heterocycles as selective inhibitors of fibrinogen-mediated platelet aggregation.

The synthesis and biological activity of novel thiazole-based heterocycles as inhibitors of thrombin-induced human platelet aggregation are described. Further evaluation of selected compounds show they inhibit platelet aggregation as stimulated by a variety of agonists. The more active compounds also were found to inhibit fibrinogen binding to platelets. To further delineate the mechanism of action of these compounds, direct binding studies with the purified glycoprotein (GP) IIb/IIIa receptor were performed. Flow cytometry analyses of 24 and 32 indicate that these compounds block the activation process of the GPIIb/IIIa receptor without denaturing the integrin receptor. On the basis of these studies, 32 exhibited the best profile as a novel nonpeptide inhibitor of fibrinogen-mediated platelet aggregation.

The new FAA national automated ECG network: some aviation medical examiner experiences.

The Federal Aviation Administration (FAA) has required, since August 1, 1987, that aviation medical examiners (AMEs) transmit by telephone all electrocardiograms (ECGs) necessary for airman "Class I" medical certification. This relatively new airman certification requirement is centralized at the Civil Aeromedical Institute (CAMI) in Oklahoma City. In calendar year 1989, the FAA received 69,000 electronically transmitted electrocardiograms. CAMI uses Marquette Electronics software to interpret the ECG signals that are received from multi-channel equipment. The single-channel transmitted ECGs are hand screened at present. The FAA "automated" screening program is unique among governmental airman medical certification programs throughout the world. This paper presents, for potential future users, the authors' experiences with the new airman automated electrocardiographic certification requirement, and covers positive and negative features involved in the implementation and operation of the program. We conclude that while the new FAA automated ECG screening program has satisfactorily replaced the former "physician-intensive" manual screening process, the new system increases the AME's equipment and operation costs. These are passed on to the airman who is seeking certification.

Food poisoning as an in-flight safety hazard.

The leading cause by far of airline pilot incapacitations is gastrointestinal illness resulting from "food poisoning". This potentially hazardous condition is inadequately dealt with by the airlines today and strikes equally in all pilot age groups. Sufficient incidents are occurring to justify more stringent aircrew meal standards and regulations. Aircrew heart attack and stroke concerns pale into insignificance relative to the far more common food poisoning incapacitations. Specific regulations on aircrew feeding should be promulgated by the Federal Aviation Administration and the regulatory authorities in other countries to preclude simultaneous-onset in-flight incapacitations due to common-source food poisoning.

N-hydroxyurea and hydroxamic acid inhibitors of cyclooxygenase and 5-lipoxygenase.

Two series of compounds (1 and 2) having structural features of the dual COX/5-LO inhibitor tepoxalin and the 5-LO inhibitor ABT-761 were prepared. Many of these hybrid compounds are potent COX and 5-LO inhibitors; two compounds (1a and 2t) inhibit eicosanoid biosynthesis in an ex vivo assay.