(all-E)-β-Apo-12'-carotenoic acid and a series of the geometrical isomers were synthesized and their biological activities to inhibit growth and to induce differentiation of human acute promyelocytic leukemia cell line HL-60 were analyzed. It was found that (all-E)-β-apo-12'-carotenoic acid (I, Fig. 1) and (15'-Z)-apo-12'-carotenoic acid (II, Fig. 1) showed strong activity both in the inhibition of growth and the induction of differentiation. The biological activity of (13'-Z)-β-apo-12'-carotenoic acid (III, Fig. 1) was modest, while that of (13', 15'-di-Z)-β-apo-12'-carotenoic acid (IV, Fig. 1) was negligible.(all-E)-β-Apo-12'- carotenoic acid and the geometrical isomers acted additively with (all-E)- retinoic acid, and synergetically with (9-Z)-retinoic acid. In accord with our previous report, biological activities of (all-E)-β-apo-14'-carotenoic acid (V, Fig. 1) and of (15'-Z)-β-apo-14'-carotenoic acid (VI, Fig. 1) were very weak. It was indicated that (all-E)-β-apo-12'-carotenoic acid, an intermediate metabolite of excentric cleavage pathway of β-carotene, per se may exert the biological function.

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A nutritional analysis was conducted on the dietary intake of a group of 6 vegan children aged 7 to 14 who had been living on a vegan diet including brown rice for from 4 to 10 years, and on that of an age-matched control group. In addition, their serum vitamin B₁₂ levels and other data (red blood cell count, hematocrit, hemoglobin, etc.) were determined in the laboratory. In vegans' diets, 2-4g of nori (dried laver), which contained B₁₂, were consumed daily. Not a single case of symptoms due to B₁₂ deficiency was found. There were no statistically significant differences between the two groups with respect to any of the examination data, including B₁₂ levels (p<0.05). Therefore, consumption of nori may keep vegans from suffering B₁₂ deficiency.

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In neonatal medicine, it is thought that retinol is useful for preventing CLD and for fetal development. However, β-carotene and other vitamin A precursors have not been studied in neonates with CLD or other disorders. Cord blood of neonates including ELBW and VLBW infants was assayed for plasma levels of retinol, RBP, β-carotene and cryptoxanthin. Plasma β-carotene levels in ELBW and VLBW were lower than that in term infants, but plasma cryptoxanthin levels in ELBW and VLBW were about the same as in term infants. Plasma retinol and RBP levels showed almost same levels during 23-41 gestational weeks. Maternal smoking reduced plasma β-carotene but not cryptoxanthin, retinol, or RBP levels. IUGR was associated with increased cryptoxanthin levels in cord blood. Serious neonatal diseases, including CLD and ROP manifested no significant effects on the cord blood vitamin levels. Thus, the occurrence of these diseases at birth could not be predicted by examination of vitamin levels in cord blood.

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In the present study, we investigated the developmental changes of:(1) plasma and erythrocyte tetrahydrobiopterin (BH4);(2) erythrocyte GTP cyclohydrolase (the rate-limiting enzyme of BH4 biosynthesis);(3) the permeability of erythrocyte membrane to BH4; and (4) plasma phenylalanine, both in healthy human subjects and Wistar rats. In vitro experiments demonstrated passive transport of BH4 into erythrocytes. In humans, BH4 levels as well as the other parameters were fairly consistent across all age groups. In contrast, Wistar rats showed significant developmental changes in erythrocyte BH4, which were not simply correlated to either GTP cyclohydrolase, permeability to BH4, or plasma phenylalanine levels. This may suggest the existence of other factors regulating the homeostasis of BH4, such as BH4-binding capacity in plasma and/or erythrocytes. These species/age differences in erythrocyte characteristics may influence the pharmacological behavior and clinical efficacy of BH4 in humans and experimental animals.

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It is known that the fortification of milk and its derivatives with iron has been recognized as a worldwide necessity, since the deficiency of this element produces different metabolic disorders. With this purpose, we have studied the iron absorption in mice after the administration of fluid milk and yogurt with FeSO₄ stabilized by microencapsulation with soy lecithin (SFE-171) or with FeSO₄, both labeled with ⁵⁹Fe, which was used in the same experimental conditions for comparative purposes. The absorption of iron is influenced by the presence of some additives which usually are ingested together with milk, such as cacao, coffee, tea, “Argentine green herbs tea or maté” or cereals. The experimental results demonstrate that the iron absorption from SFE-171 is (12.3±2.9)%, whereas that from FeSO₄ is (7.7±2.7)%, this difference is highly significant at p <0.01. In all the cases, groups of 25 mice each were used to increase the statistical robustness of the experimental results. On the other hand, it could be demonstrated that the presence of 10% w/v cacao (Nesquik^TM) increases the iron absorption in both cases, whereas 1% w/v cacao (Nesquik^TM) and maté has no influence on the iron absorption if SFE-171 is used. Cereals (Nestum^TM 3 cereals), yogurt and other additives like tea and coffee, for different reasons, decrease the absorption of this element.

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The objective of this study was to investigate the interrelationship between taurine and erythrocyte-membrane NaK ATPase activity. A comparison was conducted to test whether taurine or uric acid (a water-soluble scavenger of free radicals) prevents or recovers the depletion in membrane ouabain sensitive NaK ATPase activity resulting from ozone exposure or cholesterol enrichment of the erythrocyte membrane. A depletion of 44% and 27% in ouabain sensitive NaK ATPase activity was respectively caused by ozone exposure and cholesterol enrichment. Taurine as well as uric acid partially prevented the activity loss from ozone exposure. In addition, taurine at high concentrations (from 1.5 to 4.5 mM) restored the depletion of erythrocyte membrane NaK ATPase activity due to ozone exposure and prevented the depletion of the enzyme activity due to cholesterol enrichment. In contrast, although the same high concentrations were used, uric acid failed to show either of the above effects. These results suggest that taurine acts (1.5-4.5 mM) polyvalently as not only an antioxidizing agent but also as a membrane stabilizer to maintain the functions of membrane Na-K ATPase, a membrane-bound protein.

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The activities of enzymes in fatty acid oxidation and synthesis in the liver of rats fed soybean phospholipids and soybean oil corresponding to the dietary levels of 3% fatty acid added to the diets containing a saturated fat (coconut oil) and a polyunsaturated fat (salflower oil) at the amounts corresponding to 12% fatty acid levels were compared. Soybean phospholipid compared with soybean oil added to both coconut and safflower oil diets significantly reduced the activities of enzymes in fatty acid synthesis (fatty acid synthetase, glucose-6-phosphate dehydrogenase and malic enzyme). However, there were no significant differences in the activities of enzymes in fatty acid oxidation (carnitine palmitoyltransferase, acyl-CoA dehydrogenase and acyl-CoA oxidase) between the groups of rats fed soybean phospholipid and soybean oil added to coconut and safflower oil diets except for one occasion. Soybean phospholipid compared with soybean oil added to coconut oil diet significantly decreased the concentrations of triacylglycerol, choresterol and phospholipid in the serum and of triacylglycerol and cholesterol in the liver. However, the dietary phospholipid added to safflower oil diet failed to alter these values. These results suggested that the alteration in the rate of fatty acid synthesis, but not oxidation, in the liver is responsible for the lipid-lowering effect of dietary soybean phospholipid added to a saturated fat diet.

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We investigated the effects of dietary red pepper on the energy metabolism in male subjects. In the first experiment, after havinga standardized dinner on the previous evening, the subjects consumed a breakfast (650kcal) either with or without 10g of red pepper. For 150 min after the meal, they took a rest and their expired gas was collected. During the initial 30min after the meal, the energy expenditure tended to be higher in the red-pepper diet period than in the control diet period. For the remaining 120min, no difference in the energy expenditure was found between the red-pepper diet period and the control diet period. However the carbohydrate oxidation was significantly higher in the red-pepper diet period than in the control diet period while the lipid oxidation was lower in the red-pepper diet period than in the control diet period for 150 min after the meal. In the second experiment, the subjects consumed a breakfast with 10g of red pepper after an oral administration of propranolol or a placebo. The propranolol abolished the increase in energy expenditure during the initial 30min due to the meal containing red pepper. For the remaining 120min, no difference in energy expenditure was found between the propranolol period and the placebo period. These results suggest that an increase in the energy expenditure after the meal containing red pepper appeared only immediately after the meal ingestion and a red-pepper diet increases the carbohydrate oxidation without increasing total energy expenditure for 150min after the meal. And an increase in the energy expenditure immediately after the meal containing red pepper is considered to be caused by β-adrenergic stimulation.

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The purpose of this study was to examine the effect of different amounts of fat in enteral diets on liver function, liver lipid accumulation, and protein metabolism in septic rats. Sepsis was induced in Wistar rats by cecal ligation and puncture. The rats were divided into four groups and were fed enterally 0%(F0, n=7), 10%(F10, n=7), 20%(F20, n=8), or 30%(F30, n=9) of total calories as fat. The liquid diet consisted of medium-chain and long-chain triglyceride mixtures as the fat sources, casein oligopeptide, and dextrin (100 kcal/100 ml). Infra-duod num feeding was ended on the 6th day. Serum glutamic oxaloacetic transaminase and glutamic pyruvic transaminase activities, indices of liver dysfunction, were highest in the F0 group, and triglycerides accumulated in the livers of that group, possibly because of the large proportion of carbohydrate in the diet. Value of nitrogen balance was highest in the F 10 group, and serum total protein and albumin concentration were higher in the F10 and F20 groups than in the F0 and F30 groups. The liver protein content in the F10 and F20 groups was higher than in the F0 and F30 groups. Serum triglyceride in the F30 group was about 2 times higher than in the F10 and F20 groups. These results indicate that enteral fat administration in septic rats as 30% of total calories reduced liver dysfunction and liver triglyceride accumulation, but might have been excessive for optimal protein metabolism. Therefore, the preferable amount may range from 10% to 20% of total calories.

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Spinach was evaluated for its bioavailability of magnesium in the experiment with magnesium-deficient rats. The effect of oxalic acid on absorption of dietary magnesium was also examined in the same experiment. After there were significant differences in the body weight of the rats between the control group and the magnesium-deficient group, and after the number of dead rats increased, the magnesium-deficient rats were divided into six groups. They were pair-fed for 8 days on the magnesium-deficient diet, magnesium-deficient diet supplemented with raw powdered spinach (R-sp), boiled powdered spinach (B-sp), or fried powdered spinach (F-sp), control diet supplemented with oxalic acid (Ox-C), and control diet (+Mg). On the 10th day, there was no significant difference in the food intake of the rats between the control group and magnesium-deficient group. However, the body weight, and body weight gain of the rats increased more significantly in the control group than in those of the magnesium-deficient group. Also, the contents of calcium and phosphorus in the liver and kidneys, and serum calcium content increased significantly in the magnesium-deficient rats compared with those of the control rats. However, the serum magnesium content decreased significantly in the magnesium-deficient rats. An especially large amount of calcium was accumulated in the kidneys of the magnesium- deficient rats. At the end of the experimental period, there were no significant differences in the food intake, body weight and body weight gain of the rats among the control group and each of the spinach-added groups. The body weight and body weight gain of the Ox-C rats decreased significantly in comparison with those of the control group and each of the spinach-added groups. Although, there were no significant differences in the concentrations of serum minerals (Mg, Ca and P) among each of the groups, kidney magnesium, calcium and phosphorus, and liver magnesium and phosphorus were significantly higher in each of the spinachadded groups than those of the control, Ox-C and+Mg groups. A large amount of calcium was accumulated in the kidneys of the rats fed on the R-sp, B-sp, F-sp and Ox-C diets. However, the kidney calcium of each of the spinach-added groups markedly decreased in comparison with kidney calcium of the magnesium-deficient rats on the 10th day, when the magnesium-deficient rats were separated. There was no significant difference in the magnesium content of the left tibiae among each of the spinach-added groups. Also, the magnesium contents of the left tibiae of each of the additional groups did not reach the level of those of the control rats. The contents of calcium and phosphorus of the left tibiae were not significantly different among any of the groups except for both the R-sp and Ox-C groups, and decreased significantly in the R-sp and Ox-C groups compared with those of the other groups. A highly positive correlation between bone calcium and bone strength was not observed in this study; the breaking force of the left femurs of the B-sp and F-sp rats increased significantly in comparison with that of the Ox-C group. The rate of magnesium absorbed by the rats receiving the control, R-sp, B-sp, F-sp, Ox-C, and + Mg diets was 88.9, 80.2, 88.4, 90.4, 88.1, and 87.7%, respectively. The rate of apparent absorption of calcium from the control, Mg-deficient, R-sp, B-sp, F-sp, Ox-C and + Mg diets was 87.0, 84.1, 57.3, 66.4, 66.2, 53.3 and 83.5%, respectively. The data indicate that oxalic acid remained in spinach after cooking of boil or frizzle was not deleterious to magnesium availability, and that spinach is one of the most promising sources of magnesium.

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It has previously been proposed that the hypocalcemic action of gastrin was mediated by a gastric peptide gastrocalcin which enhanced bone uptake of calcium (Ca). The present study, thus, aimed to reconfirm the effect of gastrin on muscle and bone Ca uptake and to evaluate a possible direct effect of gastrin on tissue Ca uptake. First, we showed that human and rat gastrin (100 μg/100 g body weight (bw), s. c.) acutely increased uptake of intragastrically administered ⁴⁵Ca by the tibia and femur. Interestingly, human gastrin was more effective and also enhanced ⁴⁵Ca uptake by the gastrocnemius muscle. In order to find out whether gastrin could act directly on bone, 10μg of rat gastrin/100 g bw and ⁴⁵Ca were injected into the right femoral artery supplying the right leg while the left leg received normal saline and an equal amount of ⁴⁵Ca. At 30 min, the right gastrocnemius muscle and femur were found to contain 168% and 162%, respectively, more ⁴⁵Ca than the left leg. In contrast, daily administration of 25 μg of rat gastrin/100 g bw, s.c., for 2 weeks had no effect on muscle or bone total Ca content while the content of ⁴⁵Ca given on days 12 and 13 was lower in the tibia and femur of gastrintreated rats. It could be concluded that gastrin transiently enhanced Ca uptake by muscle and bone. However, two-week treatment with gastrin appeared to accelerate the bone turnover rate i.e., enhanced uptake and release of calcium, so that there were no net changes in bone total Ca content at the end of the experimental period.

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Triacylglycerol is digested and absorbed primarily through the action of lipase in the lingual and pancreatic juices. We used a wheat flour-derived lipase inhibitor to inhibit triacylglycerol absorption from the intestinal tract, and studied the effect on serum lipid concentration. Rats were given free access to high fat diets containing the lipase inhibitor at O (control), 0.05, 0.1 and 0.2% levels for 3 weeks, and their serum triacylglycer l, total cholesterol, and HDL-cholesterol concentrations were measured at weeks 1, 2 and 3. The measured values were significantly lower in the groups receiving the lipase inhibitor than in the control group. The degree of decrease in these respects was roughly dose-dependent. Additionally, the inhibitor intake raised the fecal lipid excretion and lowered the hepatic cholesterol level. It was, therefore, assumed that the inhibition of lipase in the digestive tract interfered with lipolysis and thereby with cholesterol absorption.

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Methyl linoleate hydroperoxides (MLHPO), a model for lipid hydroperoxides, suppressed murine natural killer (NK) cell-mediated cytotoxicity to YAC-1 cells. When NK cells were cultured with MLHPO, the conjugation of NK cells and YAC-1 cells was not affected, but most of the conjugated NK cells could not lyse YAC-1 cells. These findings suggest that NK cell-mediated cytotoxicity can be suppressed by lipid hydroperoxides.

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