Ivermectin is the 22,23-dihydro derivative of avermectin B1, a macrocyclic lactone produced by an actinomycete, Streptomyces avermitilis. It is active at extremely low dosage against a wide variety of nematode and arthropod parasites, apparently by virtue of its action on the mediation of neurotransmission by gamma-aminobutyric acid. It is now in commercial use in various countries for the treatment and control of parasites in cattle, horses, and sheep, and is expected to become available for use in swine and dogs. Since studies with the drug in man are in a preliminary stage, it is not yet known whether ivermectin will be useful in human medicine.
a Cells (Pseudon lonas ATCC 11250, E. coli K12) were grown in a special flask designed for this type of experiment6 at 25°for about 20 hours with vigorous mechanical shaking. Basal medium contained 0.15% K2HP04, 0.05% KH2P04, 0.02% MgS04-7H20 and 0.1% Difeo yeast extract. In addition, in exp. 1, 0.1% benzoic acid and 0.1% NH4C1; in exp. 2 and 5, 0.1% L-phenylalanine; in exp. 3 and 6, 0.1% L-tryptophan and in exp. 4 and 7, 0.1% glucose and 0.1% NH4C1 were added as carbon and nitrogen sources. The gas phase was a mixture of nitrogen and oxygen in a ratio of 4:1. Highly enriched 0218 gas was prepared by electrolysis of approximately 33% enriched H2018 purchased from The Weizmann Institute of Science, Israel. Cells were harvested by centrifugation, washed with 0.9% KC1 and distilled water. Pyrolysis was carried out at 500°f or 1 hour with HgCl2 as a catalyst according to D. Rittenberg and L. Ponticorvo (Internat. J. Appl. Radiation and Isotopes, 1, 208 (1956)). The mass spectrometric analyses were carried out in collaboration with Mr. W. E. Comstock of this Institute.tions involving fixation of atmospheric oxygen.6-7 When E. coli, a facultative aerobe, was grown under comparable conditions, 018-enrichment in the cell material was approximately 0.1% or less of that of the atmospheric oxygen. Although the data indicate that E. coli also incorporates atmospheric oxygen, particularly when aromatic compounds are used as carbon sources, oxygenases seem to play a more important role in the metabolism of a strictly aerobic microorganism. Further studies are in progress in order to determine the distribution of oxygenases in various tissues and other microorganisms.(5) O.
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