Oral Administration of Cyclopentane Neuraminidase Inhibitors Protects Ferrets against Influenza Virus Infection

Several cyclopentane inhibitors of influenza virus neuraminidase that have inhibitory activities in tissue culture similar to those of zanamivir and oseltamivir have recently been described. These new inhibitors have been examined for efficacy against a virulent H3N2 influenza virus when administered orally to infected ferrets. Preliminary studies indicated that oral administration of BCX-1923, BCX-1827, or BCX-1812 (RWJ-270201) at a dose of 5 or 25 mg/kg of body weight was active in ferrets in reducing respiratory and constitutional signs and symptoms, but these antivirals affected virus titers in the upper and lower respiratory tracts only marginally. Of the three compounds, BCX-1812 seemed to be the most efficacious and was examined further at higher doses of 30 and 100 mg/kg. These doses significantly reduced peak virus titers in nasal washes and total virus shedding as measured by areas under the curve. Virus titers in lung homogenates were also reduced compared to those in controls, but the difference was not statistically significant. As was observed with BCX-1812 at lower doses, the nasal inflammatory cellular response, fever, and nasal signs were reduced while ferret activity was not, with activity remaining similar to uninfected animals

Differential stimulation of post-exercise myofibrillar protein synthesis in humans following isonitrogenous, isocaloric pre-exercise feeding

.The aim of this study was to test the effects of two disparate isonitrogenous, isocaloric pre-exercise feeds on deuterium-oxide (D2O) derived measures of myofibrillar protein synthesis (myoPS) in humans. Methods: In a double-blind parallel group design, 22 resistance-trained men aged 18 to 35 years ingested a meal (6 kcal·kg−1 , 0.8 g·kg−1 carbohydrate, 0.2 g·kg−1 fat) with 0.33 g·kg−1 nonessential amino acids blend (NEAA) or whey protein (WHEY), prior to resistance exercise (70% 1RM back-squats, 10 reps per set to failure, 25% duty cycle). Biopsies of M. vastus lateralis were obtained pre-ingestion (PRE) and +3 h post-exercise (POST). The myofibrillar fractional synthetic rate (myoFSR) was calculated via deuterium labelling of myofibrillar-bound alanine, measured by gas chromatography–pyrolysis–isotope ratio mass spectrometry (GC-Pyr-IRMS). Data are a mean percentage change (95% CI). Results: There was no discernable change in myoFSR following NEAA (10(−5, 25) %, p = 0.235), whereas an increase in myoFSR was observed after WHEY (28 (13, 43) %, p = 0.003). Conclusions: Measured by a D2O tracer technique, a disparate myoPS response was observed between NEAA and WHEY. Pre-exercise ingestion of whey protein increased post-exercise myoPS, whereas a NEAA blend did not, supporting the use of NEAA as a viable isonitrogenous negative control