Anti-influenza virus activity of the neuraminidase inhibitor 4-guanidino-Neu5Ac2en in cell culture and in human respiratory epithelium.

The anti-influenza activity of the neuraminidase inhibitor 4-guanidino-Neu5Ac2en (4-G-NAc) was determined in Madin-Darby canine kidney (MDCK) cells by yield reduction and ELISA and in explants of human respiratory epithelium by yield reduction. In MDCK cells, 50% inhibitory concentrations (EC50) averaged 0.5 microgram/ml for influenza A/Virginia/88(H3N2) and 0.04 microgram/ml for A/Texas/36/91(H1N1) by ELISA, and < 0.01 microgram/ml for influenza A/Virginia by yield reduction. In human adenoid explants, concentrations causing at least 1.0 log10 TCID50/ml decrease in yield (EC90) at 48 h were < 0.01 microgram/ml for A(H1N1) and A(H3N2) viruses and 0.25 microgram/ml for B/Hong Kong/5/72. 100 micrograms/ml 4-G-NAc did not inhibit outgrowth of human adenoid epithelium at 6 days, whereas ribavirin 10 micrograms/ml reduced outgrowth by > 50%. 4-G-NAc is a potent and selective inhibitor of clinical isolates of influenza A and B viruses in human respiratory epithelium.

Urinary thromboxane A2 metabolites in patients presenting in the emergency room with acute chest pain.

OBJECTIVES: The diagnosis of acute myocardial infarction (MI) is difficult in emergency rooms where large groups of patients present with chest pain. Confirmation of the diagnosis of MI based on the myocardial band of creatine phosphokinase may take a day. A more rapid diagnostic screening procedure is desirable and for this reason we evaluated urine thromboxane. DESIGN: The study consisted of patients presenting with chest pain. Urine samples were obtained in the emergency room and on the following 5 days for those patients who were admitted to the hospital. The urine samples were used to determine the levels of immunoreactive 11-dehydro-thromboxane B2 (i-11-dehydro-TXB2) and 2,3-dinor-thromboxane B2 (i-2,3-dinor-TXB2). Myocardial infarction was defined as an increase in the myocardial band fraction of plasma creatine phosphokinase (> 5% of the total) and changes in the electrocardiogram. The patients' diagnoses were retrospectively correlated with thromboxane metabolite levels. SETTING: The present study took place in the emergency rooms of two major hospitals: Georgetown University Medical Center, Washington DC, and Fairfax Hospital, Virginia, USA. SUBJECTS: The study comprised 369 patients presenting with acute chest pain and consisted of 247 men and 122 women aged 30-94 years. MAIN OUTCOME MEASURES: The outcome measure of this study was the predictive value of i-11-dehydro TXB2 and i-2,3-dinor-TXB2, for the diagnosis of MI, in patients presenting in the emergency room with chest pain. RESULTS: Patients undergoing an MI had significantly higher levels of both thromboxane metabolites in their urine in the emergency room, when compared to patients undergoing a cardiac event other than an MI or to patients with unstable angina. Thromboxane metabolite levels rapidly returned to normal on the days following admission to the hospital. Aspirin intake appeared to significantly decrease the levels of i-11-dehydro-TXB2, but not that of i-2,3-dinor-TXB2. CONCLUSIONS: The measurement of thromboxane metabolites in the urine may provide a more rapid, accurate and cost-effective means of diagnosing MIs in patients presenting with chest pain.