Decrease of phosphorus/oxygen ratios by dinitrophenol in vivo.
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Mice were given daily per os amounts of dinitrophenol or of thyroid extract sufficient to prevent or retard the normal weight gain of uninfected animals, but not large enough to cause their death. When mice maintained on these regimens for 1 or 2 weeks were infected with staphylococci, most of them died within 12 days-much more rapidly than did mice fed a normal diet. Deaths occurred even when the organism injected was a non-virulent staphylococcus, unable to cause fatal disease in mice fed a normal diet. There was some suggestion that thyroid treatment interfered with the bactericidal mechanism in the liver, spleen, and kidneys of mice during the initial phase of infection. In contrast there was no clear evidence at any time thereafter that either thyroid extract or dinitrophenol caused the staphylococci to multiply more rapidly in the various organs.
It was found that DNP (2,4-dinitrophenol) will inhibit completely the propagation of influenza virus in chorioallantoic membrane. This reagent did not permanently alter those metabolic processes required for the synthesis of virus and at the concentrations employed demonstrated no virucidal effects. In minced preparations of chorioallantoic membrane DNP was shown to have a pronounced stimulatory effect upon ATPase (adenosinetriphosphatase). When DNP was used with intact tissues, an excellent correlation was found between the inhibition of viral propagation and the stimulation of respiration and release of phosphate. Concentrations of DNP which permitted a twofold increase in the endogenous respiration of intact membranes allowed little or no viral synthesis. It is concluded that the energy required for viral synthesis derives from the oxidative phosphorylative activity of the host tissue.
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