2-Amino-5-bromo-6-methyl-4-pyrimidinol (U-25,166) induced high levels of circulating interferon in mice when administered either parenterally or orally. Peak titers of interferon were found in the serum between 6 and 12 h after inoculation of the drug. Lower but significant levels of interferon were found in rat serum after administration of U-25, 166 by either the intraperitoneal or oral route, and good levels of circulating interferon were observed in cats after oral treatment. Repeated intraperitoneal doses (50 mg/kg) of U-25, 166 protected mice against intranasal encephalomyocarditis virus challenge. The minimal effective acute oral dose for antiviral activity was approximately 250 mg/kg. This was also the minimal dose that produced detectable levels of interferon. Maximum tolerated doses in mice were four to six times the minimal effective doses. A single oral treatment was protective in mice against challenge virus inoculated 24 h later. The compound protected mice from challenge with high levels of encephalomyocarditis virus, up to 20,000 mean lethal doses. Antiviral activity in mice was retained when certain minor substitutions were made in the U-25,166 structure.
The oxygen tension at the skin surface, when the atmospheric oxygen supply is excluded, may be measured polarographically. If the experimental subject is seated in a room at 25 °C and his arm is in a box at 33°C, spontaneous fluctuations in skin surface oxygen tension can be seen because of fluctuating blood flow in the superflcial skin vessels (Evans & Naylor, 1967). An array of cathodes in a single electrode has been used to measure the fluctuations in blood flow which are occurring simultaneously at seven different points in the skin. If a long recording of such fluctuations is made, spectral analysis of the fluctuations shows that most of the power is concentrated at the lower frequencies but reveals no clearly deflned preferred frequency. It is clear however from the fluctuation patterns that recurring bursts of activity do occur with quite well deflned periodicities in the range 30 s-5 min. There is a stronger correlation between the fluctuations occurring at points on the skin less than i mm apart than between points further apart, although there are clearly some components which are common to points separated by up to 5 mm. These results suggest that the fluctuations may be a result of a common central effect which can then be modifled or overridden by peripheral mechanisms controlling blood flow. REFERENCE EVANS, N.T.S. & NAYLOR, P.F.D. (1967) The systemic oxygen supply to the surface of human skin. Respiration Physiology, 3, 21.The three common types of skin cyst (epidermoid cyst, pilar cyst and steatocystoma multiplex) are
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