Evidence was obtained that fumagillin inhibits RNA synthesis in the microsporidian, Octosporea muscaedomesticae, a pathogen of the blow fly, Phormia regina. Infections, treated with 66 mg fumagillin per liter of 5% sucrose for six hours, were compared to control octosporeoses of the same age with the following techniques: Giemsa stain, pyronin-methyl green, and acridine orange fluorescence. Staining reactions demonstrated an almost complete loss of material from the parasites' cytoplasm; RNase treatment of normal parasites identified this material as RNA. Parasite DNA remained unchanged after fumagillin treatment, as observed by the above techniques.
Actinomycete cultures extracts and leaves extracts of high plants were tested in vivo against foot and mouth disease virus. A virus strain "O" adapted to mice muscle and twenty-one-day-old 10-13 g male mice as laboratory animals were used. From the experimental results the survival index was obtained. Out of 63 assayed Actinomycete strains five were active, as regard plants 3 out of 36 were active. Various inoculation schemes were assayed. A single dose of extracts administered 24 hours before infection produced a significant survival index from which it is possible to infer the existance of an indirect viral inhibitory mechanism. Also it was proved that there is no inhibitor that acts in vitro in treated animals serum. It has not yet been possible to obtain a purified active substance from the extracts and also it was observed that the extracts loose gradually their activity.
The plasma level and tissue distribution of sulfocillin administered by intravenous, intraperitoneal, intramuscular or subcutaneous routes into mice, rats, rabbits and dogs, were compared with those of carbenicillin. The drug level was measured as active penicillin by a biological assay method using Bacillus subtilis PCI 219 as a test organism. The recovery rates of penicillins from the mixture with phosphate buffer homogenates of the tissues in vitro varied depending on the individual tissues and animal species, and in many cases the recovery rate of sulfocillin was higher than that of carbenicillin. A single dosage of sulfocillin or carbenicillin in all administration routes produced the highest plasma and tissue levels 5-15 minutes after injection in all animal species tested. Measurable concentrations of penicillin in plasma and tissues were detected up to 2 hours after administration in mice and rats, whereas they were detectable for 4-6 hours after intramuscular injection in rabbits and dogs. The levels of sulfocillin and carbenicillin in the liver and kidney were higher than in plasma in mice and rats, but not in rabbits. On the other hand, the levels of both penicillins in the lung and spleen were lower than in plasma and no measurable concentration of penicillin was detected in the brain. Urinary and biliary excretions of sulfocillin and carbenicillin were also studied. Amounts of both penicillins recovered from the 6-hour urine or bile sample in rabbits were similar. However, when sulfocillin and carbenicillin were given in dogs, the recovery rates in urine and bile were markedly different. When sulfocillin was administered, as much as 20% of the given dose was recovered in the 6-hour urine and about 50% of dose was recovered in the 6-hour bile. On the other hand, with carbenicillin, about 65% of the dose was recovered in the 6-hour urine and about 23% of the dose was recovered in the 6-hour bile.
Cyclamidomycin (CAM) inhibited the growth of E. coli in a progressive manner even at high concentrations and the effect was abolished by washing the cells in a CAM-free medium. Among cellular macromolecular syntheses, nucleic acid synthesis was most sensitive to CAM. In the presence of CAM, nucleic acid precursors in the cellular pool were not incorporated into nucleic acids but were degraded and released into the medium. The nucleoside diphosphokinase activity of the 100, 000×g supernatant from E. coli was inhibited by CAM, leading to the conclusion that this enzyme is involved in the mechanism of action of this antibiotic.
Oryzoxymycin (I), an antibiotic produced by Streptomyces venezuelae var. oryzoxymyceticus, is unstable and easily dimerizes to an inactive crystalline product. Structural study of this product led to the conclusion that the structure of oryzoxymycin is D-2-[(+)-6-amino-trans-5-hydroxy-1, 3-cyclohexadienel-carbonyloxy]-propionic acid: