METABOLISM OF INTRAVENOUS METHYLNALTREXONE IN MICE, RATS, DOGS AND HUMANS

were observed in rats. Dogs produced only one metabolite, MNTX-3-glucuronide (M9). In conclusion, MNTX was not extensively metabolized in humans. Conversion to methyl-6-naltrexol isomers (M4 and M5) and MNTX-3-sulfate (M2) were the primary pathways of metabolism in humans. MNTX was metabolized to a higher extent in mice than in rats, dogs, and humans. Glucuronidation was a major metabolic pathway in mice, rats and dogs, but not in humans. Overall, the data suggested species differences in the metabolism of MNTX

Nonmigrating tides in the mesosphere and lower thermosphere.

The study of waves is integral to understanding the atmosphere as a whole. Solar diurnal tides are global scale gravity waves excited by the sun's diurnal heating of minor atmospheric species in the lower atmosphere. Tides increase in amplitude as they propagate upwards and are the most important dynamic feature in the equatorial mesosphere and lower thermosphere. This thesis presents analyses of the first observations of nonmigrating diurnal tide signatures in the mesosphere and lower thermosphere from High Resolution Doppler Imager winds and temperatures. Through a global comparison of both winds and temperature, we find prominent equatorial features which we interpret as the zonally symmetric and eastward nonmigrating diurnal tides. The observed latitudinal structure of these tides correspond well to different modes predicted by linear tidal theory. We find that the second symmetric mode is prominent in the zonally symmetric and wavenumber one tides. The gravest antisymmetric mode and the gravest symmetric or Kelvin mode are the main features in zonal wavenumbers two and three. Our analysis shows that the amplitudes of the tides generally increase with altitude and maximize within 90--110 km. The dominant symmetric modes in the zonally symmetric meridional wind and temperature, show increasing phase with altitude suggesting either in situ or higher level forcing or possible aliasing. We investigate the degree and implications of this aliasing in the context of both theory and data. We also expand a satellite-relative Fourier analysis technique to cope with aliasing in future satellite missions. We use the retrieved vertical structures of wavenumber three tidal modes to infer thermal dissipation rates. Our calculated thermal dissipation coefficients show a scale dependence between the modes that is in agreement with theory. We develop an equivalent gravity wave model that incorporates linear dissipation and mean zonal winds to Prandtl numbers from the thermal dissipation and the observed complex vertical wavenumbers. These calculated Prandtl numbers are of order one. Mechanical dissipation is then computed from the Prandtl number and thermal dissipation. Our derived dissipation coefficients are roughly two to three times larger than those of more constrained previous studies.Ph.D.Physics, Atmospheric SciencePure SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/132016/2/9938550.pd