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.
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.
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.