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Nutritional myopathy has been induced in both rats and lambs by feeding diets low in selenium. The distribution of 45Ca, administered as 45CaCl2, has been examined firstly by autoradiography, and secondly by measuring the excretion of 45Ca in urine and faeces. Autoradiographs of skeletal muscle from unsupplemented animals showed radioactivity over discrete muscle fibres at a stage when no abnormalities were apparent using conventional staining techniques. Similar retention of 45Ca was found in some of the tubules in the kidneys of selenium-deficient rats. Total excretion in urine and faeces of lambs, examined for 48 h after intravenous administration of 45CaCl2, showed that in normal animals 18-6% of the dose was excreted, whereas in dystrophic lambs 12-0% was lost. The difference was significant at the 2% level. The respiratory rates of isolated skeletal muscle mitochondria, measured polarographically in the presence of glutamate and pyruvate as substrates, were low for dystrophic rats. Respiratory control indices were 1-0 for the same preparations but for supplemented rats they were all above 1-0. The differences in respiratory rates were significant at the 1% level. The major conclusion drawn from the results of these experiments is that one of the first effects of sleenium deficiency which can be visualized is the abnormal retention of calcium by individual muscle fibres.

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The fate of selenium, given as Na2(75)SeO3, or [75Se]selenomethionine, and of [35S]methionine administered intravenously to ewes and lambs, has been examined. The main intention was to follow the incorporation of selenium into protein in a number of tissues, including liver and kidney, and to measure the extent of that incorporation of selenoamino acid, particularly with respect to the administration of selenite. The ewes chosen were lactating ewes with lambs at foot, and the lambs were animals which had been weaned on to fodder low in selenium and were recovering from white muscle disease with selenium therapy. These two experimental situations were chosen as they offered conditions under which selenium incorporation might be considered to be maximal. Entry of isotope into milk was rapid and was greater when 75Se was given as the selenoamino acid than as selenite. In both ewes and lambs greater amounts of activity, derived from selenite, were bound to plasma proteins than to the proteins of milk. This was particularly evident in samples taken some hours after administration. This ability of the plasma to bind selenium was demonstrated by alkaline dialysis. Small, though significant amounts of selenium, derived from Na2(75)SeO3, were incorporated as selenoamino acids into the proteins of liver, kidney and pancreas, as well as into the proteins of milk and plasma. In ewes, both selenomethionine and selenocystine were identified chromatographically in enzyme digests of defatted liver and kidney. Some differences occurred in the distribution of labelled compounds in organs from lactating ewes and recovering lambs. The incorporation of selenium into protein is discussed briefly in relation to the recent findings of an association between selenium and the enzyme glutathione peroxidase.

PIP: A comparison of the uptake of selenium (Se) 75 selenite, Se 75 selen omethionine and Se 75 methionine by tissues of ewes and lambs is presented. Included in the study were 3 lactating ewes with lambs at foot and 3 lambs which had been weaned on to fodder low in selenium and were recovering from white muscle disease with Se therapy. Isotope entry into milk was rapid and was greater when Se 75 was administered as selenoamino acid than as selenite. Alkaline dialysis demonstrated that greater amounts of activity derived from selenite were bound to plasma proteins than to the protein of milk, particularly in samples taken some hours after administration. Small amounts of Se 75 selenomethionine were incorporated as selenoamino acids into the proteins of liver, kidney, pancreas, milk and plasma. Selenomethionine and selenocystine were identified chromatographically in enzyme digests of defatted liver and kidney of the ewes. Some differences were seen in the distribution of labelled compounds in organs from the ewes and lambs. Recent findings of an association between selenium and glutathione peroxidase are discussed in relation to the incorporation of selenium into protein.

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The activity and distribution of the selenium-containing enzyme, glutathione peroxidase, has been determined in muscle fractions in normal adult rats and sheep. Skeletal and cardiac muscle have been examined, and in both types of muscle the major proportion of the enzyme appeared in the cytosol fraction. Enzyme activity was higher in cardiac muscle than in skeletal muscle in both species, and based on total protein present in fractions, it appears that rat muscle contains more enzyme activity than sheep muscle. In tissues from lambs born to selenium-deprived ewes the levels of enzyme were significantly depressed. Two sampling periods were selected, the first when the lambs were 2-3 weeks of age and the second at slaughter when they were 10 weeks old. Muscle, plasma and erythrocyte levels of the enzyme indicated that the most sensitive measure of selenium deficiency is likely to be that of the erythrocyte enzyme level.

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