The monoclonal antibody 1A1D-2 has been shown to strongly neutralize dengue virus serotypes 1, 2 and 3, primarily by inhibiting attachment to host cells. A crystal structure of its antigen binding fragment (Fab) complexed with domain III of the viral envelope glycoprotein, E, showed that the epitope would be partially occluded in the known structure of the mature dengue virus. Nevertheless, antibody could bind to the virus at 37 degrees C, suggesting that the virus is in dynamic motion making hidden epitopes briefly available. A cryo-electron microscope image reconstruction of the virus:Fab complex showed large changes in the organization of the E protein that exposed the epitopes on two of the three E molecules in each of the 60 icosahedral asymmetric units of the virus. The changes in the structure of the viral surface are presumably responsible for inhibiting attachment to cells.
1 Alprazolam, a triazolobenzodiazepine, is extensively prescribed for the treatment of anxiety disorders, which predominantly affect women of child-bearing age. The purpose of the present study was to assess the pharmacokinetics of alprazolam and its two hydroxylated metabolites: 4-hydroxy-alprazolam and a-hydroxy-alprazolam in lactating human volunteers and to test the predictability of four recently reported models for drug transfer into milk based on physicochemical properties. 2 Multiple milk and serum samples in eight lactating subjects were collected up to 36 h following single oral doses of 0.5 mg alprazolam; suckling of the infant was discontinued after drug administration. 4-Hydroxy-alprazolam was the predominant metabolite in serum samples while a-hydroxy-alprazolam was not detected.
The escalating number of blood specimens from late-fed premature or very sick newborns greatly increases the risk of missing the diagnosis of phenylketonuria (PKU). Babies receiving antibiotics have uninterpretable "clear-zone" results with the traditional Guthrie bacteriologic inhibition assay (BIA). For the past year the authors have reexamined the blood phenylalanine level on specimens giving the "clear-zone" effect by BIA by use of the McCaman-Robins chemical-fluorescent assay (CFA). Spuriously high blood phenylalanine levels occurred in four babies who were receiving ampicillin and whose specimens were collected on filter paper and autoclaved in preparation for the BIA. None of the babies proved to have PKU. The fluorescent interference caused by ampicillin resulted from the heat of autoclaving the specimen. The authors recommend that the blood specimen should not be autoclaved before analysis by either BIA or CFA.
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