HALOGENS AND THEIR MODE OF ACTION
The extensive use of various forms of chlorine and iodine as antiseptics has resulted in the accumulation of much information about efficiency of these halogens under various circumstances. There has been considerable study given to the factors affecting their germicidal activities and to the mechanisms of these effects.' Much less is known about bromine?. a* The qualitative similarities and quantitative differences in many of the properties of chlorine, bromine, and iodine afford an excellent opportunity for observing the effects of certain isolated factors on germicidal activity. Accordingly, this paper will be concerned, for the most part, with the extent to which a few basic chemical properties of the halogens, such as hydrolysis, ionization, and formation of complexes can be used to explain quantitative dfierences in antiseptic power. The mechanism of the reactions leading to the death of the organism will not be discussed here. The interested reader is referred to another paper in this series and to a published report6 for information on this subject. One would expect that the rate of bactericidal action would be characteristic of the particular halogen compound present. Under usual conditions of use, however, one may have present, in addition to elemental halogen, hypohalous acid formed by hydrolysis, hypohalite ion from ionization of the acid, complex ions involving elemental halogen with halide ion, and N-halogen compounds. Furthermore, factors such as concentration, pH, and temperature should have quantitatively different effects on the germicidal activities of the three halogens because the equilibrium constants of the reactions involved are different. Most of the work leading to quantitative conclusions has been carried out with bacterial spores, beginning with Levine and co-workers,6 Meyers,' Tilley and Chapin: and others. The advantages of using B. metiens spores, for example, have been pointed out by Charlton and Levine9 and need not be enumerated here. Accordingly, in FIGURE 1, we consider the comparative action on B. meliens spores over a suitable concentration range of chlorine,'O bromine, and iodine" at pH 7 and room temperatures. A solution of each halogen free of added halide was added to a buffered distilled water suspension of spores, extraneous organic matter being excluded as far as possible. The log of the time for 99 per cent kill is plotted against the log of the normality of the solution. Calculation shows that under these conditions chlorine exists chiefly as hypochlorous acid and bromine entirely as hypobromous acid, but iodine is present as molecular iodine. It is then not surprising that the usual order of halogen reactivities is not found and that iodine fails to show less germicidal power than bromine. It might be of some interest to note that on a weight concentration basis, iodine is considerably less active than chlorine, although still more active than bromine. Against
EVIDENCE OF THYROXINEFORMATION FOLLOWING IODINE ADMINISTRATION IN SPRAGUE-DAWLEY RATS
Iodine (/2)has been proposed to be used as a water disinfectant on the manned space station. Previous work has shown that subchronic administration of '2 to SpragueDawley rats in drinking water significantly increases plasma thyroxine/triiodothyronine (T4fTy levels. This is not observed with iodide (/-) treatment. The present study addresses the possibility that '2 reacts with deiodinated T4metabolites in the gastrointestinal tract to resynthesize T4' Incubation of diiodothyronine (T2)' Ty or reverse TJ with '2 in phosphate-buffered saline resulted in the formation of T4 as measured by radioimmunoassay. Washes from the initial segments of the small intestine of the rat show that substrates are present that react with '2 to produce T4' Single oral doses of '2 to rats produced significant dose-related increases in serum T4 and decreases in TJ concentrations after 2 h. Administration of an equivalent dose of ,did not alter significantly plasma T4 concentrations. Higher concentrations of a radioactive substance that bound a T4-speciFicantibody are present in plasma of animals treated with 12512compared to 125,-. These data support the hypothesis that '2 reacts with metabolites of thyroid hormone in the gastrointestinal tract to resynthesize T4and elevate its levels in blood.
Target of inhibition by the anti-lipogenic antibiotic cerulenin of sterol synthesis in yeast.
Abstract The antibiotic cerulenin inhibited the incorporation of 14 C-acetyl-CoA by 67% at a concentration of 9 × 10 −6 M but not that of 14 C-HMG-CoA into the non-saponifiable fraction in a cell-free extract of Saccharomyces cerevisiae . Cerulenin markedly inhibited the activity of partially purified HMG-CoA synthase. No inhibition of acetoacetyl-CoA thiolase activity was observed in the same preparation of HMG-CoA synthase. Therefore, cerulenin inhibition of overall sterol synthesis may be accounted for by the specific inhibition of HMG-CoA synthase activity.