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Studies of the generalized Shwartzman reaction produced by diet. II. Feeding of fractions of oxidized cod liver oil.

By molecular distillation of oxidized cod liver oil a partial isolation of the lipid species responsible for the diet-induced generalized Shwartzman reaction in pregnant rats has been achieved. Molecular distillation produced three fractions and a residue. Qualitative and quantitative differences in each fraction were shown by determining iodine and saponification numbers and by thin layer chromatography on silicic acid. The incidence of the Shwartzman reaction was higher with fraction III than with either of the other two fractions, the residue, or the original oxidized cod liver oil. It is evident that the toxic factor or factors can be concentrated by molecular distillation. The high temperatures used in the molecular distillation destroy peroxides in the lipids. Therefore, in spite of the fact that oxidation of dietary fats is necessary to produce the reaction, peroxides in the dietary lipid are not necessary for the development of the tissue reaction. The residue fraction contains high molecular weight polymers and the incidence of the Shwartzman reaction is low in animals fed this material. It is unlikely that high molecular weight polymers are responsible for the tissue reaction. Animals that do not gain weight at a rate close to that of the normal pregnant rat do not develop the reaction. Conversion of fraction III into its ethyl esters increased the incidence of the Shwartzman reaction in two experiments. Esterification appears to "unmask" a certain amount of the active factor. The specific lipid material or materials responsible for the development of the generalized Shwartzman reaction remains to be found.

Animals↗

The effect of diet on the fecal bacterial flora of mice and on their resistance to infection.

A study was made of the effect of certain dietary regimens on the lactobacillus flora in the stools of mice and on their resistance to infection. Semi-synthetic diets with purified casein or wheat gluten as sole source of protein, gave rise to much smaller numbers of viable lactobacilli in the stools than did other diets containing unidentified natural products-as present for example in mixtures of whole wheat and whole milk, or in certain commercial pellets. Furthermore, one of the lactobacillus types with rhizoid morphology disappeared completely from the stools of animals fed the semi-synthetic diet. The change in the lactobacillus flora became apparent within a very few days after the animals had been shifted from the complex to the synthetic diet Moreover, this change was not completely reversible. Whereas the total numbers of lactobacilli increased when the animals were shifted back from the synthetic to the complex diets, the rhizoid lactobacilli which had disappeared completely from the stools reappeared only slowly or not at all. In twelve consecutive experiments the three diets which gave rise to the large numbers of lactobacilli in the stools also conferred on the mice a much higher resistance to experimental infection with Staphylococcus aureus and Klebsiella pneumoniae, than did the semi-synthetic diets. However, direct evidence has not yet been obtained that the two kinds of phenomena were causally related. Following administration of endotoxin there was a rapid and very large increase in the numbers of enterococci and coliform bacilli in mice fed the semi-synthetic casein diet, but not in those fed the pellets. In two preliminary experiments carried out with another colony of mice, not pathogen-free, it was also found that the rhizoid type of lactobacilli disappeared from animals fed the semi-synthetic casein diet while enterococci and coliform bacilli progressively increased in numbers under the same conditions. The dietary effects on the lactobacillus flora, and on resistance to experimental infection, were equally pronounced whether the mice were housed in individual cages on wire grids, or grouped in larger cages with wood shavings as litter. This was true even if the bedding was changed only once weekly and became therefore grossly soiled.

Animals↗