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1. Vitamin A: There are very few reports on vitamin A deficiency in Japan because of the rising national status of nutrition, while vitamin A deficiency is still an important nutritional problem in developing and poorly developed countries. In the pediatric field, relationship between vitamin A nutrition and the mechanism for development of bronchopulmonary dysplasia have been discussed, since vitamin A acts as a protector from the keratinization of epithelial cells in the mucosal layer and the skin. The changes in the lung tissues with inadequately supplied vitamin A, probably cause the chronic lung disease resulting from mechanical ventilation in neonates, in whom the plasma vitamin A and retinol binding protein levels are usually low. 2. Vitamin E: In keeping with the view that newborn infants and especially premature infants suffer from vitamin E deficiency. On the basis of recent findings of the vitamin E content in the neonatal cells, the previous concept would agree, as an existing marginal deficiency in neonates. The neurologic deficits manifested in a beta-lipoproteinemia is confirmed to be vitamin deficiency in humans. It has also become clear that similar neurologic impairment occurs in other chronic fat malabsorptive states, such as cholestatic liver diseases, extensive resection of the gut. More recently several patients with spinocerebellar degeneration from vitamin E deficiency without other evidence of malabsorption in whom progression of the diseases is terminated by the vitamin E therapy (isolated vitamin E deficiency) have been reported. The above items are discussed.

1. Vitamin E content in the adipose tissue was examined in rats with and without vitamin E deficiency. With the progression of vitamin E depletion, the more rapid decrease in tocopherol concentration was observed in brown adipose tissue (BAT) than in white adipose tissue (WAT), and the rate of decrease of tocopherol was approximately three times faster in BAT than in WAT. After the intramuscular administration of 10 mg/kg of all-rac-tocopheryl acetate twice a week for two weeks to vitamin E-deficient rats, a similar pattern of increase was observed in the tocopherol concentrations of BAT and WAT, although the rate of increase was slower in WAT than in BAT. 2. Changes of tocopherol concentration in BAT and WAT were investigated in normo-nourished rats with hyperlipemia produced by the intramuscular injection of Triton WR-1339 for 7 days. A marked increase in tocopherol concentration was observed in both BAT and WAT in the late period of hyperlipemia, with the increase being greater in WAT. 3. The fatty acid composition of adipose tissue was compared between rats with and without vitamin E deficiency. No significant differences were observed in BAT and WAT between the two groups. 4. The glucose uptake of WAT was not altered in vitamin E-deficient rats when compared with control rats.

Nutritional status of vitamin E was assessed in very low birth weight infants of less than 1,500 g, with respect to changes in plasma and red blood cell (RBC) tocopherol concentrations. The forty infants examined were divided into two groups in terms of their birth weight: group A, less than 1,000 g; and group B, 1,000-1,500 g. Immediately after birth, plasma tocopherol level was 335 +/- 101 micrograms/dl in group A and 316 +/- 103 micrograms/dl in group B, while RBC tocopherol was 187 +/- 48 micrograms/dl and 231 +/- 72 micrograms/dl packed PBCs, in groups A and B, respectively. In two infants, RBC tocopherol concentrations were less than 115 micrograms/dl, this level being reported as the lowest of the normal range. After birth, plasma and RBC tocopherol levels decreased markedly during 4 to 6 weeks of life especially in group A, while no decrease below normal range was documented in RBC levels in group B. A fine granule preparation of tocopheryl nicotinate (20 mg/kg/day) was administered in seven other infants, three in group A and four in group B. All three infants in group A showed no elevation of plasma and RBC tocopherol levels during the first 4 or 5 weeks of the administration, but a marked elevation thereafter. In three of the four infants in group B, an elevation of plasma and RBC tocopherol concentrations was documented after 2 weeks of the administration. The above findings indicate that no deficiency exists even in very low birth weight infants immediately after birth, while the deficiency may develop after birth, due to a poor ability to absorb fat.

The plasma and red blood cell (RBC) levels of alpha-tocopherol in rats were determined in association with hemolysis induced by dialuric acid for a 7-week period of tocopherol deprivation following a 2-week period on tocopherol-containing diet. The patterns of decreases in plasma and RBC levels during the 7-week period were similar, differing in one respect. The RBC levels were characterized by a prompt decrease to non-detectable levels in the 4th week, while at that time a plasma level of 100 microgram/dl, albeit low, was maintained during the subsequent two weeks. Consequently, tocopherol ratios of RBC to plasma lowered throughout the experimental course. As for the relationship between these levels and hemolysis values, non-hemolysis was recorded in animals whose minimum RBC and plasma levels were 40 microgram/dl packed cell and 180 microgram/dl, respectively. This experiment showed that the plasma tocopherol level which has traditionally been accepted as the only index of hemolysis values does not always reflect them, and that in animals with hemolysis, only RBC tocopherol levels were found to reflect hemolysis values.

The oxidation of vitamin E-deficient rat red blood cells (RBCs) induced by the hypoxanthine-xanthine oxidase (HX-XOD) system has been performed in an aqueous suspension. The generation of chemiluminescence and the accumulation of thiobarbituric acid-reactive substances (TBARS) were observed initially and were followed by hemolysis. Interestingly, the total counts of chemiluminescence were closely related to the amount of TBARS. The predominant change of membrane proteins induced by the reaction was the depletion of spectrin bands in gel electrophoresis. When RBC ghosts were oxidized with HX-XOD, the sulfhydryl (SH) groups of membrane proteins decreased at an early stage of the incubation, which was coincident with the above protein alteration. Membrane alpha-tocopherol suppressed not only the formation of TBARS but also chemiluminescence and hemolysis; nevertheless, it did not inhibit the protein damage and the loss of SH groups. Moreover, it was concluded that the chemiluminescence observed during the oxidation of RBC membranes was associated mainly with the peroxidation of lipids and only to a minor extent with the oxidation of proteins.

As the assessment of the nutritional status of vitamin E, the validity of red blood cell (RBC) tocopherol concentration was examined in relation to tocopherol concentration in the liver and in its subcellular fractions. When 10 mg/kg of dl-alpha-tocopherol was injected intramuscularly to vitamin E deficient rats, plasma tocopherol reached a maximum level earlier than did RBC tocopherol and liver tocopherol. However, as the correlation in tocopherol concentrations between RBC and plasma and between RBC and tissue homogenate or its subcellular fractions was examined with respect to all the values examines during the study courses, a moderately close correlation was observed between RBC and liver tissue and between RBC and the subcellular fractions while a lack of correlation was found between RBC and plasma. When rats sufficient in vitamin E were depleted for 8 weeks by a vitamin E deficient diet, tocopherol concentrations decreased in a similar pattern in the plasma, RBC, and liver and its subcellular fractions. In this case, a very close correlation in the tocopherol concentrations was observed between RBC and other subjects, i.e., the plasma, liver homogenate and its subcellular fractions.

A procedure to induce hemolysis by the hypoxanthine-xanthine oxidase reaction was developed and applied to vitamin E deficient red blood cells (RBCs) in rats. The reaction system was as follows: 0.16 mM hypoxanthine, 0.05 U/ml xanthine oxidase in 2.5% RBC suspensions with an isotonic buffer (pH 7.4) containing 10 mM phosphate buffer and 125 mM saline (277 mOsm). Hemolysis was observed to depend on the vitamin E concentrations in the RBCs. Hemolysis was inhibited by catalase but not by SOD. After the reaction with vitamin E deficient RBCs, an increase in TBARS in the aqueous phase of the reaction mixture was observed. This accompanied the increase in fluorescent substances in the lipid extracts, in association with a significant decrease in the PE and PS of the RBCs, and a decrease in arachidonic acid in membrane lipids. The above changes were almost completely inhibited by tocopherol incorporated into vitamin E deficient RBCs.