STUDIES ON THE PROPHYLACTIC EFFECT OF CARZINOPHILIN ON POLIOVIRUS INFECTION IN MICE
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Several substances were reported to have chemoprophylactic effect on poliovirus infection in animals; e.g., benzimidazole, helenine, and statoln.In a previous study in our laboratory, antitumor antibiotics such as quinomycin, miromycin, carzinostatin, and chromomycin A3 were found to be effective prophylactically on poliovirus infection in mice. The present study revealed that carzinophilin exhibited a preventing effect on poliovirus infection in mice, and the mechanism of the prophylaxis was studied.To examine the protective effect of carzinophilin, mice were injected intraperitoneally with 2, 500-10, 000u/kg of the antibiotic. Twenty-four hours later, the animals were challenged intraperitoneally with 10 LD50 of virus. Mortality of the mice was reduced from 100% in the control group to 20 or 40% in the treated group with 2, 500 or 5, 000u/kg of carzinophilin. When mice were infected with 100 LD50 of the virus, administration of carzinophilin did not prolong the life span of the animal, although it did appear to produce a delay in the onset of paralysis.To examine the effect of carzinophilin on reproduction of poliovirus in the mouse brain, the following experiments were carried out. A group of mice was injected intraperitoneally with 10, 000u/kg of the agent 24 hours prior to the infection with 100 LD50 of virus via intraperitoneal route. The treated and the control mice were sacrificed 24 hours after infection, and the amount of the virus present in the brain of each animal was determined. Virus titers in the brains of all control mice ranged from 104.6 to 105.5 TCD50, whereas no virus titer was detected in the brains of seven out of eight treated mice and only one exhibited a virus titer of 105.5 TCD50.Other groups of mice were similarly pretreated with the agent, and the treated and the control mice were sacrificed 3 and 6 hours after infection. The virus titers in the liver and blood were determined, but no difference was observed between the treated and the control. No inhibition by carzinophilin of the virus reproduction in the brain was observed, when the virus was inoculated intracerebrally. Carzinophilin had no inactivating effect on the virus, and had no effect on the yield and cytopathogenicity of the virus in HeLa cells.Finally, virus titers in the brain which was perfused with saline were examined as early as 3 and 6 hours after virus inoculation to determine the amount of virus adsorbed to or penetrated via the "blood-brain barrier". At 3 hours, no difference was observed in the virus titer between the treated and the control mice, but an inhibition of virus growth was observed in the treated mice at 6 hours.These results suggest that the prophylactic effect of carzinophilin on poliovirus infection may not be due to the inhibition of virus reproduction in target cells but due to the effect of the agent on the blood-brain barrier.
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