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1. The effect of dietary protein level and supplementation with thyroxine on the liver storage of vitamin A, on the fraction of liver vitamin A in the alcohol form, and on the plasma levels of vitamin A and proteins has been studied in chicks.
2. Liver storage was reduced by lowering the dietary protein level.
3. Protein restriction lowered the percentage of vitamin A found in the liver as retinol.
4. Thyroxine increased both vitamin A storage and the fraction of the total vitamin A as retinol, this effect being dependent on dietary protein level.
5. Plasma vitamin A and plasma protein contents were lowered to a highly significant extent by protein restriction. This drop was essentially caused by reduction of the albumin fraction in chicks fed on a 5% protein diet and by a reduction of β- and γ-globulins in chicks fed on a 10% protein diet.
6. Thyroxine supplementation of the diet lowered to a highly significant extent plasma protein content; this reduction was caused by a dramatic fall in the level of plasma albumin. The β- and γ-globulins were concomitantly increased.
1. When weanling rats were given a vitamin E-deficient diet and 0.15% (w/v) silver acetate in their drinking water, there was a high incidence of liver necrosis and death after 2–4 weeks. This was prevented by 120 ppm D-α-tocopheryl acetate in the diet, was partially prevented by selenium at 1 ppm but not at 0.05 ppm and was only marginally prevented by 0.15% DL-methionhe.
2. All these effects were observed when the diet was free of fat and when it contained either methyl oleate or polyunsaturated methyl esters. The polyunsaturated lipid slightly increased the velocity of the terminal illness.
3. In spite of the ‘anti-vitamin E’ effect of Ag and the clear demonstration that α-tocopherol played a major part in preventing toxicity, experiments with tracer amounts of [5-Me-14C]-D-α-tocopherol showed that rather than there being any destruction of tocopherol in the critical period preceding the onset of disease, there was an increase in tocopherol in the liver due to Ag administation. The metabolism of tocopherol in the remainder of the animal was unaffected during the pre-necrotic phase.
4. The results are inconsistent with the view that the stress induced by Ag is caused by a pro-oxidant effect, either in the gastro-intestinal tract or in the tissues of the rat. They show that lipid peroxidation is not a causal factor in the aetiology of Ag-induced liver necrosis and suggest that stress in the vitamin E-deficient animal probably raises the requirement for tocopherol.
1. The activities of several lysosomal hydrolases have been measured in tissues of rats with nutritional liver necrosis. Incipient or actual liver necrosis did not alter total, free or unsedimentable activities of cathepsin, β-glucuronidase, β-galactosidase or acid phosphatase of liver and kidney. Free hydrolytic activity towards p-nitrophenyl phosphate was slightly raised in liver, and serum β-galactosidase and β-glucuronidase were moderately elevated. These results suggest that lysosomal hydrolases are not directly implicated in the causation of liver necrosis.
2. Testicular degeneration was studied with reference to changes in β-giucuronidase activity. This enzyme activity, total, free and unsedimentable, was raised in deficient rat testis at 6 months old and did not decline even after a year. Raised values were also found in serum.
1. Samples of whale, meat, fish, groundnut and soya-bean meals and skim-milk powders were assayed microbiologically with Tetrahymena pyriformis W and Streptococcus zymogenes for available methionine and available lysine.
2. Detailed collaborative studies on the assay of available methionine with Strep. zymogenes were conducted on the effects of dry- or wet-grinding the test meals, the use of crude or purified papain for predigesting the ground meals and the use of optical density or titratable acidity as criteria of bacterial growth response.
3. Wide differences were observed in the available methionine and available lysine contents of a variety of meals in the preliminary studies, with a promising measure of interlaboratory agreement in the assay of available methionine with Strep. zymogenes.
4. As a result of detailed collaborative studies a provisional method is proposed for the assay of available methione with Strep. zymogenes, adopting dry-grinding and predigestion with an agreed level of papain in the preparation of the meals. No general recommendation could be offered on the comparative merits of optical density and titratable acidity as criteria of bacterial growth response.
1. Among a series of 343 children with severe primary malnutrition there were 248 for whom, on admission, there were reliable records of age, weight, height, liver size, severity of oedema, skin lesions and angular stomatitis, and concentration of total serum protein, haemoglobin and sodium. For eighty-four of these children the serum bilirubin concentration was also known.
2. The correlations of these characteristics of the children on admission, with mortality, and with the rate of recovery were investigated.
3. Age, weight, oedema and haemoglobin concentration were not significantly related to mortality or to rate of recovery. A multiple regression analysis showed that an increased serum bilirubin concentration and a decreased serum sodium concentration indicated a bad prognosis, and these two factors contributed almost the whole of the multiple correlation coefficient of 0.63 with respect to mortality and 0.59 with respect to speed of rccovery.
4. We conclude that in our series of children death was more closely associated with liver failure or overhydration than with protein depletion, and suggest that the administration of ton much protein or water to an acutely ill malnourished child may precipitate death.
5. This analysis shows that the mortality observed in our series cannot be adequately explained by any combination of the characteristics considered above; there must, therefore, be other factors of importance for which we do not have suitable measurements.
1. One hundred and ten weanling rats were distributed between five dietary groups in randomized blocks. Each block was constructed from within a litter and each member of the block received a different diet.
2. The main features of the diets were: group I (twenty-six rats) 72% sucrose, group 2 (sixteen rats) 72% uncooked maize starch, group 3 (sixteen rats) 72% roll-dried maize starch, group 4 (twenty-six rats) 36% sucrose and 36% uncooked starch, group 5 (twenty-six rats) 36% sucrose and 36% roll-dried starch.
3. The animals were killed after 20 days on the diets and assessed for dental caries. The rats of group 1 (sucrose) had significantly more caries than all other groups, the rats of group 2 (uncooked starch) had significantly less caries than any of the other groups. Roll-dried starch (group 3) produced significantly more caries than uncooked starch (group 2). The mixture of uncooked starch and sucrose (group 4) was significantly more cariogenic than the mixture of roll-dried starch and sucrose (group 5).
1. A series of experiments was carried out to determine the minimum essential amino acid requirements of the adult rat.
2. After testing four amino acid patterns taken from the literature, a basal pattern was formulated in which each amino acid appeared at the lowest level at which it was presented in any of the original diets.
3. Nitrogen balance was the main criterion used to judge any benefit arising from modest increases in individual amino acids tested in a modified Latin-square design. They were given at a protein level of 3.6% of the diet. Non-essential amino acids were in the same proportions as in whole egg.
4. It appeared that three amino acids, namely tryptophan, threonine and isoleucine, brought about more favourable balances when presented at concentrations higher than basal.
5. Reduced levels of each amino acid were then tested in order to ensure that no surpluses were present.
6. N retentions indicated that lysine, phenylalanine plus tyrosine, leucine and valine could be reduced below the basal level and still meet the needs of the rat for these amino acids.
7. When the pattern of amino acids arising from these latter trials was tested in combination, rather than as trios, pairs, or single changes, positive N balances gave confidence that these were minimal levels of the essential amino acids required for meeting the maintenance needs of adult rats.
8. Plasma proteins from the rats on the evolved pattern were found to be in no way different from those found for normal animals. This gave further support to the belief that the pattern was adequate for the rats.
1. Eleven groups of male rabbits (eight to eleven per group) were given ad lib. a diet consisting of 61 parts of a low-fat basal ration to which were added: for groups 1–3, 20 parts maize oil; for groups 4–7, 20 parts butterfat; and for groups 8–11, 0.47 parts maize oil and 43.1 parts wheat starch. Different types of roughage were added to the 61 parts of basal ration as follows: for groups 1, 4 and 8, 19 parts ground wheat straw; for groups 2, 5 and 9, 19 parts Solkafioc; for groups 3, 6 and 10, 19 parts of shredded cellophane; and for groups 7 and 11, 14 parts shredded cellophane and 5 parts peat.
2. After the rabbits had been given the experimental diets for a period of 40 weeks, the plasma cholesterol levels were determined. The animals were then killed and the degree of atheromatous degeneration was determined after the aortas had been stained with Sudan IV.
3. Elevated levels of plasma cholesterol and extensive atheromatous degeneration were observed in the rabbits given the diets containing 20% butterfat (groups 4–7) and in those given the diets containing 48% starch (groups 8–11). Lower levels of plasma cholesterol and only slight atheromatous degeneration were observed in the rabbits given the diets containing 20% maize oil (groups 1–3).
4. The levels of plasma cholesterol and the degree of aortic atherosis were influenced very markedly by the nature of the dietary roughage. Plasma cholesterol levels and degrees of aortic atherosis tended to be higher when cellophane was the roughage component than when wheat straw was the roughage component of the diet. The replacement of part of the cellophane of the diet by peat reduced the level of plasma cholesterol and the degree of aortic atherosis.
5. The possible mechanisms by which the nature of the dietary roughage influences plasma cholesterol levels are discussed.
1. The effect of a penicillin-enriched diet (100 mg or 1000 mg penicillin-G/kg food) on the active transport of D-glucose and L-histidine has been investigated by the use of sacs of everted small intestine of normal young adult rats and golden hamsters. The antibiotic was given for up to several weeks.
2. The penicillin made no difference to the final concentration gradients of D-glucose or L-histidine achieved by rat small intestine, although with the hamster these appeared somewhat improved. Water entry into the serosal fluid remained unchanged.
3. The lengths and the dry weights of the small intestines of both species were not altered by the dietary regimen.
1. The protein efficiency ratio of three protein sources was determined with rats by a depletion-repletion method. The sources were: a groundnut product, a methionine-supplemented groundnut product and lactalbumin.
2. Livers obtained from the test animals were assayed for arginase activity, and kidneys for transamidinase activity (glycine amidinotransferase).
3. The measurements indicated that there was an inverse relationship between arginase activity and the nutritive value of the dietary protein.
4. Transamidinase activity was also influenced by nutritive value. Only the unsupplemented groundnut product, which had the lowest nutritive value, failed to produce a significant increase of transamidinase activity over basal levels.
5. The findings are discussed from the standpoint of physiological function and needs. It is suggested that observed levels of arginase activity are not necessarily related to amounts of urea excreted; similarly, transamidinase activity may be well in excess of physiological requirements.
1. The activities of several lysosomal hydrolases were measured in the tissues of chicks suffering from nutritional muscular dystrophy, encephalomalacia or exudative diathesis.
2. In dystrophic breast muscle, β-glucuronidase was raised five- to six-fold, cathepsin fourfold and acid phosphatase 1.5-fold. No change was found in the subcellular distribution of β-glucuronidase.
3. Chicks with encephalomalacia showed no changes in the β-glucuronidase, β-galactosidase, acid phosphatase or β-acetylglucosaminase activities of cerebellum or brain. Subcellular distribution of β-glucuronidase and β-galactosidase in these tissues was also unchanged.
4. In exudative diathesis, hydrolases were found in the exudate, and there was increased activity in the subcutaneous tissue first showing haemorrhages. Increased hydrolytic activity was found in liver, spleen and kidney. Breast muscle was not always affected by the exudative condition, but, when it too degenerated, its hydrolase activity increased.
5. β-Glucuronidase activity was measured in the serums of chicks suffering from each of the three deficiency diseases. None of the diseases caused a rise in activity.
1. A study has been made of the protein requirements for maintenance and for growth of children about 1 year old who had recovered from malnutrition. 2. The diets used supplied 120kcal/kg daily; the sole source of protein was dried skim milk. 3. The average maintenance requirement, measured by nitrogen balance, was found to be 100 mg N/kg day. At this level of intake the net protein utilization (NPU) of cow's milk protein approached 100. 4. An intake of 200 mg N/kg day was enough to produce normal growth and N retention. 5. The amount of N retained was 2.9 g/100 g weight gain, indicating that no excess of fat was being laid down. 6. These results are in close agreement with theoretical studies of the protein requirement of children at this age.
1. The blood sugar, lactate and pyruvate levels of sixty-nine Ugandan children, during treatment for kwashiorkor, have been studied. 2. The majority of untreated cases had low levels of blood glucose but high levels of lactate and pyruvate. Children with the lowest glucose levels had the lowest serum protein values and gained weight more slowly. 3. The response of the blood glucose to glucagon or adrenaline was twice as great at the end of treatment as at the beginning. 4. In children whose treatment was successful the lactate and pyruvate levels gradually fell to the normal range. There was a rise in the blood glucose value but after 3 weeks the level was still below that found in normal African children. In a few children who died or whose treatment was complicated by pyrexia and general apathy there was a rapid fall in lactate and pyruvate concentration to abnormally low levels.