Interferon-alpha (IFN-alpha) subtypes were separated by HPLC from the IFN mixtures produced by virus-stimulated human lymphoblastoid cells and leukocytes. Together with preparations of lymphoblastoid IFN and recombinant IFN-beta, these were tested in three human tumor cell lines derived from liver, lung, and neuroblasts. Their relative antiviral activities differed markedly: subtype IFN-alpha 8 was the most potent and IFN-alpha 1 the least. The results were broadly similar in all three cells, with some minor differences. when the same preparations were tested for inhibition of thymidine incorporation, the relative activities were quite different: subtypes IFN-alpha 10, IFN-alpha 17, IFN-alpha 21, and IFN-alpha 5 were now the most active, and IFN-alpha 2 was the least active. IFN-alpha 1 and IFN-alpha 8 had comparable intermediate activity. Thus, the differences in activity were not caused by degradation of some subtypes during their separation. IFN-alpha 8 not only had the greatest antiviral activity but also, like IFN-beta, induced an antiviral state in U1 mutant cell lines, which lack the tyrosine kinase, Tyk2, required for signal transduction by other IFN-alpha subtypes.

The efficacy of a number of bispyridinium compounds, including both oxime and non-oxime derivatives, has been determined against poisoning by sarin, soman, tabun and VX in guinea-pigs receiving various supporting treatments. In conjunction with atropine therapy only, the oximes were effective against sarin and VX poisoning and of them only the 4-substituted oximes were beneficial against tabun poisoning. None of the compounds was effective against poisoning by soman. When the supporting drug treatment consisted of pyridostigmine pretreatment and therapy with atropine and diazepam (this treatment itself gave considerable protection against organophosphate poisoning) both the non-oxime and oxime derivatives increased the protection against all four agents although obidoxime and TMB-4 were not beneficial against soman poisoning. The results are discussed in relation to published studies in which these compounds have been found to be beneficial against soman poisoning in atropine-treated rats and mice. It is suggested that the guinea-pig is a better model for predicting the efficacy of treatments for organophosphate poisoning in primate species.

No abstract

The effectiveness of pyridostigmine pretreatment against soman poisoning has been determined in rhesus monkeys and marmosets receiving atropine therapy. Pretreatment with the maximum sign‐free dose (200 μg kg−1, i.v.) raised the subcutaneous LD50 of soman by a factor of 28 in rhesus monkeys and 15 in marmosets. Theprotection afforded by a quarter of the sign‐free dose of pyridostigmine was not significantly less. These levels of protection are higher than any reported in non‐primate species.