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  • Animals  (1)
  • Life and Medical Sciences  (1)
  • 1
    ISSN: 1432-1238
    Keywords: Fentanyl ; Absorption ; Safety ; Intratracheal administration ; Animals ; Intensive care unit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objective To study the pharmacokinetics and local tissue effects resulting from the intratracheal administration of preservative-free fentanyl. Design Prospective, randomized, blinded and controlled animal study. Setting University research laboratory. Subjects Eighteen adult male New Zealand rabbits. Interventions Preservative-free fentanyl citrate or normal saline was administered by the intratracheal (i.t.) and intravenous (i.v.) routes to randomized groups of rabbits. The animals were killed at 24, 48 and 72 h following administration. Measurements and main results Plasma concentrations of fentanyl were measured before administration and at 2, 5, 10, 30, 60 and 120 min following administration by a specific radioimmunoassay. A detailed histological examination of the lung and tracheal tissue was performed to identify local side effects. There were no significant differences in the plasma fentanyl concentrations resulting from the i.v. or i.t. route of administration. In both groups, the concentrations of fentanyl were within the therapeutic range (i.t. 2.37 ng/ml, i.v. 2.53 ng/ml) by 2 min after injection and reached a maximum concentration within 5 min. The bioavailability of i.t. fentanyl was 71%. Microscopic examination of the respiratory system did not show significant differences between the two random groups overall. However, in the sub-group of animals killed at 24 h, more animals in the i.t. group showed signs of inflammation in the lung parenchyma. Conclusions There is rapid absorption of fentanyl following i.t. administration. Pharmacokinetic parameters for fentanyl were not significantly altered by the route of administration. Although there were no signs that i.t. administration of preservative-free fentanyl produces lung injury, a transient and mild inflammatory response was detected at 24 h after administration
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 0749-503X
    Keywords: Saccharomyces cerevisiae ; vacuolar ATPase ; VPH2: VMA12 ; Life and Medical Sciences ; Genetics
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology
    Notes: Strains bearing the vph2 mutation are defective in vacuolar acidification. The VPH2 gene was isolated from a genomic DNA library by complementation of the zinc-sensitive phenotype of the mutant. Deletion analysis localized the complementing activity to a 1·2 kb DNA fragment. Sequence analysis of this fragment revealed the presence of a single open reading frame that encoded a protein of 215 amino acids. Computer analysis indicated that the protein, which has a predicted molecular mass of 25 286 Daltons, has two distinct membrane-spanning domains. Biochemical studies indicated that strains bearing the vph2 mutation have greatly reduced levels of vacuolar proton pumping and ATPase activity and that the nucleotide binding subunits of the multimeric vacuolar H+-ATPase failed to be correctly targeted to the vacuolar membrane. The vph2 mutant fails to grow on YEP glycerol medium and on media containing 100 mM-CaCl2 or 4 mM-ZnCl2 or buffered to pH 7·5, a phenotype observed in strains carrying deletions in the genes encoding several vacuolar H+-ATPase subunits. The VPH2 gene is identical to the VMA12 gene (T. Stevens and Y. Anraku, personal communication).
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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