To break the vicious circle between malnutrition and severe infection which has been linked to the great majority of infant deaths worldwide, we have been conducting clinical and experimental studies to search for measures which provide rapid enhancement of body defenses. Based on animal experiments and clinical observations of malnourished states, it appears that nutritional deprivation affects various components of the body's defense system to various extents, cell-mediated immunity (CMI) being the most susceptible. The complement system acts to maintain host defense even when CMI is impaired. Also observed was the earlier recovery of serum complement to normal or higher levels as compared with that of CMI. The complement system responded to bacterial infection much earlier than other immunological responses, even in malnourished rats with depressed CMI. The infected rats showed a much higher rate of de novo synthesis of complement proteins than noninfected rats, and this effect was predominant in the malnourished group. Based on these experiments, we attempted to induce rapid heightened resistance to infection in malnourished rats by enhancing the complement system. After administration of lentinan or chlorophyllin, which are known to activate C3 in vitro, heightened resistance to bacterial infection was induced together with a heightened complement response. These activators enhanced C3b formation and iC3b formation in vivo, eventually resulting in enhanced interaction of iC3b present on invaders with CR3 on phagocytic cells.

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Dietary protein, xenobiotics or excess amino acids affect cholesterol metabolism. Whey protein exhibited a greater hypocholesterolemic effect in comparison with casein or soybean protein. The effect of soy protein peptic hydrolyzate or β-lactoglobulin tryptic hydrolyzate in suppressing the increase in the serum cholesterol level exceeded that of soy protein. In the case of high cholesterol feeding, dietary proteins affected serum cholesterol levels and inhibited cholesterol absorption through changes of micellar cholesterol solubility in the intestine, accompanied by an increase of fecal steroid excretion. Dietary peptides derived from β-lactoglobulin or soy protein inhibited cholesterol absorption in CaCo-2 cells. Dietary proteins affect the nature of bile acid micelles in the intestine, confirming observations by freeze-fracture transmission electron microscopy. Dietary proteins regulates the expression of the hepatic apolipoprotein gene. Dietary excess tyrosine or xenobiotics caused hypercholesterolemia characterized by an increase of both HDLcholesterol and LDL+VLDL-cholesterol. The stimulated synthesis of cholesterol in the liver is the main reason for this. The causal interrelationship between the hypercholesterolemia induced by dietary xenobiotics and the secretion of catecholamines or thyroid hormones was observed. These results indicate that the changes in cholesterol metabolism induced by dietary proteins, xenobiotics or excess tyrosine are expressed through intestinal and hepatic events.

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We measured serum mineral levels before and after inpatient treatment of 26 diabetics in order to determine the effect of diet treatment, especially restricted diets. The mineral and dietary fiber contents of the diet for diabetes were also measured. The analyses were performed on 1, 200kcal and 1, 840kcal hospital-supplied diets for diabetes actually served to inpatients on each of 31 days. Serum iron and serum calcium were significantly lower after treatment than before, and serum copper tended to be lower. Serum zinc levels hardly changed, but the serum levels of zinc enzyme alkaline phosphatase were significantly lower after treatment. The actual measurements of minerals in the diet used for diabetes showed that there was a strong possibility of deficient intake of elemental iron, zinc and magnesium, in addition to calcium and copper. Actual measurements of dietary fiber did not show any tendency for excessive intake. Thus, deficient mineral intake in the diet used for diabetes appeared to have a major influence on the decreased serum mineral levels observed after treatment.

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The multiplicity of alcohol dehydrogenase (ADH) isozymes was examined in the liver and stomach of Mongolian gerbils. Four ADH isozymes were resolved and distinguished on the basis of their electrophoretic mobilities, tissue distributinns, and substrate and inhibitor specificities. Compared with the ADH isozyme systems reported previously in the mouse, rat and guinea pig, class I and II ADHs were identified in the liver and class IV ADH in the stomach of the Mongolian gerbil. Class III ADH was detected in both organs. Thus, the ADH systems of the Mongolian gerbil seem to be identical to thase of other rodents. Liver ADH of the Mongolian gerbil showed similar activity to those of the mouse and rat, and was significantly higher than that of the guinea pig, towards either 15mM ethanol or 5mM hexenol. However, stomach ADH activity in the Mongolian gerbil, as well as that of the guinea pig, was much lower than those of the mouse and rat for both substrates. The activity in both species was also much lower than the liver ADH activities even at higher concentrations of ethanol, although ADH activities in the mouse and rat for 500mM ethanol were abvut twice as high in the stomach as in the liver. Accardingly, the first-pass metabalism of alcohol in the stomach would appear to proceed to a lesser extent in the Mongolian gerbil and guinea pig. Furthermore, the lower activity of stomach ADH for hexenol found in the Mongolian gerbil and guinea pig seems to reflect the feeding habits of these animals.

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We investigated the effects of Kabosu (Citrus sphaerocarpa Hort.) fractionated by several treatments on serum and liver cholesterol levels in rats. Kabosu fruits were pressed and separated into the Kabosu pomace (KP) fraction and juice. An ethanol precipitate (EP) fraction was obtained from 1l of juice by adding 0.71 l of ethanol. A hexane extract (HE) fraction was then obtained from EP by hexane extraction. The residue was designated the hexane residue (HR) fraction. In experiment 1, male SD strain rats aged 4 week were fed on a high-cholesterol diet supplemented with each fraction of Kabosu for 14 days. Serum and liver cholesterol levels were significantly decreased in the EP and HR groups. In experiment 2, rats were fed on a PCB (polychlorinated biphenyl) -containing diet supplemented with each fraction of Kabosu for 13 days. Serum and liver cholesterol levels were significantly decreased in the KP, EP and HR groups. In both of the experiments, when the fractions possessing the cholesterol-lowering activity were administered to rats, the amounts of excreted fecal bile acids and neutral sterols were increased. From these results, it is suggested that promotion of bile acid and neutral sterol excretion into feces is a possible mechanism for the cholesterollowering effect of Kabosu. We consider that the functional material is not fat-soluble because the cholesterollowering effect was not observed in the HE fraction.

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Using rat, we investigated the effects on cholesterol metabolism of an ethanol-precipitated fraction of Kabosu (Kabosu Juice Residue: KJR) obtained from 1l of Kabosu juice by adding 0.71l of ethanol. Male Sprague-Dawley strain rats, 4 weeks of age, were fed on a high cholesterol diet containing KJR. Serum and liver cholesterol levels decreased as the amount of administered KJR increased, and the excretion of fecal bile acids and neutral sterols was promoted. The secretion rate of cholesterol from the liver to the blood was lowered by the administration of KJR. From these results, promotion of the excretion of fecal bile acids and neutral sterols and depression of the secretion of cholesterol from the liver to the blood were considered to be the major mechanisms responsible for the cholesterol-lowering effect of KJR. The activity of the cholesterol-lowering effect of KJR was not weakened by administration of KJR which had been dry-heated or autoclaved.

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The biotin content of infant formulas made in Japan was determined. There was a large difference in the average content of total biotin between Japanese and United States products. The total biotin contents of 11 Japanese starting and follow-up formulas and 23 special formulas were 1.04±0.36μg and 0.40±0.39μg/ 100kcal on average, respectively. The biotin content of most Japanese products was considerably lower than the value (1.5μg/100kcal) recommended by the AAP (American Academy of Pediatrics) and FAO/WHO. These findings suggest that Japanese infant formulas should be appropriately improved to maintain active growth and good health of infants. Also the importance of biotin as a food additive should be recognized in Japan.

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Some metabolites related to Umami (Japanese flavor) in the adductor were measured after transfer of scallops from aerobic to anaerobic conditions for 12h. The cellular level of succinic acid increased linearly up to 12h in proportion to the accumulation of lactic acid, and was about 5 times higher than that in aerobic scallop. The ATP level did not show any significant change for the initial 3h, and then decreased rapidly. Changes in the ADP and AMP levels reflected those of ATP, and the AMP level was about twice as high as that in aerobic scallop at the end of acclimation. The arginine level decreased gradually in proportion to acclimation time. However, no striking decrease in other free amino acids, including glutamic acid, glycine and alanine, was found during acclimation. These results indicate that the increase of metabolites related to Umami is attained by transferring scallop to anaerobic conditions.

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Male rats and mice were fed diets containing kibinago (white-striped blue sprat: Spratelloides japonicus), under constant dietary levels of protein (20%), fat (5%) and cholesterol (0.5%). Casein was used as a control protein. Kibinago reduced the serum cholesterol concentration in the test animals. The concentration of serum triglyceride in the kibinago group was lower than that in the control group in both species. Feeding of defatted kibinago to mice did not influence serum lipid levels. Cholesterol concentration in the liver was comparable between the control and the kibinago groups in rats and mice, but was lower in the defatted kibinago group than in the control group in mice. Kibinago and defatted kibinago decreased the hepatic triglyceride level in mice. Feeding with kibinago reduced fecal neutral steroid excretion and increased fecal acidic steroid excretion, resulting in the reduction of total steroid excretion. However, the effect of dietary kibinago on fecal steroids disappeared when it was defatted. These results suggest that the hypocholesterolemic effect of kibinago is attributable to its lipid fraction, whereas non-lipid components contribute to the reduction of hepatic lipids.

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A study was conducted to investigate the in vivo oxidation of α-linolenic acid and linoleic acid as an energy substrates. Rats received an intravenous infusion of 1- [¹⁴C] -α-linolenic acid and 1 [¹⁴C] -linoleic acid for 3h. Cumulative excretion of expired ¹⁴CO₂ for 24h was significantly higher after infusion of α-linolenic acid (66.7±10.6%) than affter linoleic acid (49.3±5.6%). Radioactivity in the tissue at 24h after infusion was 1-2% in the liver, <0.5% in the adipase tissue, and <0.1% in the plasma, spleen and muscle. The radioactivity in the liver and adipose tissue was significantly lower after infusion of α-linolenic acid. Fram these resuits, it is suggested that α-linolenic acid is preferentially oxidized and utilized as an energy substrate compared with linoleic acid.

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