fed newborn rats was demonstrated successfully. The cytoprotective effect of prostaglandins on the gastrointestinal tract is being investigated. The significances of these studies are: (1) the demonstration of in situ biosynthesis of prostaglandins, thromboxanes, and prostacyclin and the catabolism of prostaglandins by the mammary gland; (2) the transfer of prostaglandins from the maternal circulation system to the milk seems to be of less value than the de novo synthesis of prostaglandins by the mammary gland; and (3) the confirmation of a suitable animal model with necrotizing enterocolitis. 5 Technological Objective 2: Determine the requirements for mineral intake The purpose of this program is to (1) provide data needed to develop an RDA for copper and chromium; (2) establish the essentiality to man of two or three additional trace metals (selenium, nickel, vanadium, and manganese are currently under study); (3) develop a firm base for diet recommendations for zinc, calcium, and magnesium for certain age-sex groups for which the limited data require extrapolation or inferences from research on other populatin groups; (4) quantitate the role of other nutrients in altering human needs for calcium and magnesium, and determine the physiological consequences of a less-than-optimum dietary intake; and (5) provide needed data on the chemical forms of iron, zinc, copper, and chromium that are biologically effective. Beltsville, Maryland. Zinc supplementation found needed by pregnant women Hispanic women (108) were randomly assigned to a treatment of 20 mg of zinc and a prenatal vitamin and mineral capsule. A control group (n=106) received only the vitamin and mineral capsule. Final serum zinc levels and zinc supplementation were significantly correlated. The correlation was most pronounced among women (n=45) who took the most capsules. Infant body weights were correlated with the use of supplements containing zinc. No relationship was found between maternal hair and serum zinc concentrations or between maternal hair and zinc supplementation. Calculated 24-hour dietary zinc intake was less than 50% of the RDA. Results of this study indicated that pregnant women with marginal zinc nutriture need zinc supplementation. Zinc deficiency caused testicular damage in the rat Beltsville, Maryland. Testicular damage associated with zinc deficiency in prepubertal and postpubertal rats was studied. The data suggested that a prepubertal, short-term zinc deficiency causes degenerative changes that can be repaired by zinc repletion. In contrast, the degenerative changes of the testes of post pubertal, zinc-deficient rats were not reversible. If the data are relevant to humans, some types of testicular atrophy may be associated with inadequate zinc nutriture. Glucose depressed phosphate transport in the everted gut sac - Beltsville, Maryland. In studies of intestinal phosphate-transport mechanisms in the rat, the flux of both phosphate ions and water was measured in everted gut sacs instead of measuring radioactive phosphate, the conventional method. This new approach demonstrated that in addition to its uptake of phosphate, the intestinal tissue spontaniously secretes a significant amount of phosphate during the assay. The overall flux of phosphate was dependent on the concentration of phosphate in the incubation medium and on the presence of various carbohydrates. Specifically, glucose apparently depressed phosphate transport without inhibiting spontaneous secretion, thereby resulting in reduced efficiency in the net transport of phosphate. Mineral and protein interactions influenced dietary requirements for zinc, copper, iron, calcium, and magnesium Grand Forks, North Dakota. Balance studies were conducted with about 40 volunteers who were fed mixed, U.S. diets that provided about 8% or 15% of energy from protein and that contained various souces of dietary fiber. Multiple stepwise regression analysis of the data revealed previously unrecognized interactions that influence and can be used to predict dietary requirements for zinc, copper, iron, calcium, and magnesium. Predictors tested for element requirements were as follows: (1) for zinc (Zn)--Zn balance; calcium (Ca), phosphorus (P), and nitrogen (N) intakes; and interactions among the predictors; (2) for copper (Cu)--Cu balance; Zn, P and N intakes; and interactions among the predictors; for iron (Fe), Ca and magnesium (Mg)--balance of the element; intakes of N and P; and the interactions among the predictors. On the basis of the data, requirements for Zn, Cu, Ca, and Mg can be calculated in relation to the dietary content of the major predictors. Mild zinc deficiency produced in human subjects - Grand Forks, North Dakota. Volunteers were fed mixed diets providing 3.0-3.8 mg of zinc daily for about 16 weeks after a control period of 5 weeks, followed by a rehabilitation period of 3-5 weeks. The plasma zinc trend was downward, but the lowest levels did not reach the range generally considered abnormal. The subjects retained zinc during the first 8 weeks of depletion. Then their zinc losses progressively increased until they were in negative balance by the end of depletion. Balances of calcium, magnesium, phosphorus and copper were not affected. Urinary catecholamines increased markedly in dopamine and norepinephrine excretion during the first half of zinc depletion and the first few days of repletion. Indices of riboflavin and folate status were abnormal during depletion, but recovered with repletion. Acuity of taste and adaptation to darkness were not adversely affected. The bioavailablility of zinc from cereals made from corn intrinsically labeled with Zn determined Grand Forks, North Dakota. Volunteers were fed unbrowned corn grits and corn flakes intrinsically labeled with 65zn in an experiment to determine the effects of browning (Maillard reaction) on the bioavailability of zinc. The corn was labeled at the ARS Plant Metabolism Laboratory in Fargo, ND. The corn grits and corn flakes were prepared at the Northern Regional Research Center, Peoria, Illinois. Preliminary results indicated that similar amounts (40-50%) of zinc are absorbed from both cereals but that when corn flakes are fed, up to 35% of the absorbed zinc is rapidly excreted and has a biological half-life of 5-12 days. Thus, the net amount of zinc available for utilization was substantially greater when volunteers were fed unbrowned corn grits than when they were fed corn flakes. Effect of dietary copper on response of fats to dietary cholesterol and cholic acid determined Grand Forks, North Dakota. In rats, the hypercholesterolemia caused by dietary cholesterol and cholic acid was decreased by the addition of copper to chow. When the doses of cholesterol and cholic acid were decreased, the hypercholesterolemia was eliminated by dietary copper. This experiment forges a link between the hypothesis that lipids induce atherosclerosis and the hypothesis that copper is involved in the etiology of ischemic heart disease. Dietary cholesterol and cholic acid may increase the copper requirement. 7 Copper deficiency produced cardiac abnormalities in rats - Grand Forks, North Dakota. Among 40 rats made deficient in copper, 16 developed ventricular neurysm, 9 had hemathorax, 7 had plural effusion, 3 had cardiac rupture, and 2 had hemopericardium. Fourteen rats had none of those abnormalities and some had ore than one abnormality. The abnormalities that developed are similar to hose commonly found in people who die of ischemic heart disease. ffects of dietary iron on iron-zinc interaction determined Grand Forks, North akota. True daily zinc absorption was determined in rats fed a diet high in ron (220 ppm Fe; 16.5 ppm Zn), one with adequate iron (30 ppm Fe) and one high a iron with varying levels of vitamin B6 or a constant level of picolinic cid (200 ppm). Zinc absorption in rats fed the diet high in iron was ignificantly less than that in rats fed the diet with adequate iron. Zinc bsorption in rats fed the diet high in iron, with supplemental picolinic acid, as markedly increased and did not differ from that in rats fed the diet with Jequate iron. Zinc absorption increased as the level of dietary vitamin B6 as increased. The concentration of picolinic acid in the pancreas also ncreased as the level of dietary vitamin B6 was increased. The results uggested that a high level of dietary iron inhibited zinc absorption, in part y competing, for binding, with endogenous picolinic acid. 3say for picolinic acid in plasma developed Grand Forks, North Dakota. By he use of this assay picolinic acid (PA) was quantitated in plasma from normal numan subjects and volunteer subjects fed varying levels of tryptophan. The oncentration or picolinic acid in humans generally ranges from 9.5 to 15 pmol. olunteers fed 210 mg of tryptophan daily had a plasma PA concentration of 13.5 .01. When the daily tryptophan intake of these volunteers was increased 600 g/day, the plasma PA concentration increased to 30-50 μmol. The effect of this acrease on zinc balance has not, as yet, been determined. Iffect of picolinic acid on absorption of zinc by body organs demonstrated rand Forks, North Dakota. One group of rats was injected with 100 gZn-histidine, and another group of rats was injected with 100 μg 865zn aipicolinate. The results suggested that zinc dipicolinate is absorbed by rapidly proliferating tissue or tissues involved in zinc absorption, but zinc histidine is taken up by the organs involved in excretion. Addition of zinc dipicolinate to diets of lactating rats promoted zinc transfer to fetus and lactating pups Grand Forks, North Dakota. During the last week of pregnancy and for 1 week after delivery, female rats were fed diets that contained either zinc acetate or zinc dipicolinate. The liver and kidneys of the pups from females given zinc dipiolinate contained a significantly greater concentration of zinc than did those of pups from females fed zinc acetate. results suggested that the feeding of zinc dipicolinate to female rats promotes more rapid transfer of zinc to the fetus and lactating pups than does zinc acetate. Grand Forks, The Antagonistic interaction between nickel and copper confirmed North Dakota. The antagonistic interaction between nickel and copper in rats was confirmed. If copper, or copper plus iron, deprivation was not too severe, or was too mild, signs of copper deficiency were more severe with than without nickel, and that effect was greater when dietary nickel was 50 μg/g than when it was 5 ug/g. Nickel supplementation did not significantly depress the level of copper in liver or plasma of copper-deficient rats. This finding indicated that nickel did not exacerbate copper deficiency signs by interfering with copper absorption. It also supported the suggestion that nickel substitutes for copper at some functional sites. Iron deprivation probably did not influence the 8 interaction between nickel and copper by interfering with copper absorption because, when dietary copper was adequate, iron deprivation elevated the level o: copper in liver. Preliminary findings indicated that iron deprivation elevated the level of nickel in some tissues. Thus, iron deprivation may have hi an effect on copper deficiency similar to that from elevation of dietary nckel. Asenic deprivation produced nutritional deficiencies in the rat Grand Forks, Nth Dakota. Successive generations of rats were used in tests of arsenic deprivation so that they would be exposed to deprivation throughout fetal, n natal and adult life. Fetal mortality was greater with arsenic deprivation in without. Arsenic-deprived pups exhibited depressed growth, hematocrits, t a hemoglobins, as well as elevated plasma urea, plasma alkaline-phosphatase a ivity, and liver content of copper and manganese. Preliminary findings also ivicated that arsenic deprivation depressed brain weights, depressed the sathesis of plasma triglycerides and of hepatic phosphatidyl choline, and evated the activity of plasma glutamate-pyruvate transaminase. The data sported earlier findings that suggested that arsenic is an essential element for the rat. Ierrelationship found between boron and cholecalciferol in chicks Grand Forks, North Dakota. An interrelationship was found between boron and colecalciferol in chicks. Boron markedly elevated the growth of cholecalciferol-deficient chicks, but not that of cholecalciferol-adequate cocks. Similarly, the activity of plasma alkaline phosphatase and the heart wight/body weight ratio were apparently unaffected by dietary boron in c...lecalciferol-adequate chicks. However, the cholecalciferol-deficiencyinduced elevation in the alkaline-phosphatase activity of plasma and the heart wight/body weight ratio was greater in boron deprived than in beron-supplemented chicks. Also, rachitic long bones were found in 17 of 21 bacon-deprived chicks and in 9 of 22 boron-supplemented chicks fed the cholecalciferol-deficient diet. These findings suggested that boron modulates the function of cholecalciferol or is necessary for the efficient metabolism of cholecalciferol. Effects of dietary treatments on the absorption or bioavailability of nickel in humans demonstrated Grand Forks, North Dakota. The bioavailability of nickel for humans was evaluated by giving an oral dose of nickel and then determining the change in nickel concentration in the plasma. After the standard dose of nickel (5 mg) in water, nickel concentrations in plasma rose above the baseline fasting level. No significant change from the fasting levels resulted when nickel was added to either a typical Guatemalan meal or an American breakfast. Whole cow's milk, coffee, tea, orange juice, ascorbic acid, and NaFeEDTA, but not Coca Cola or phytic acid, depressed the bioavailability of the standard dose of nickel administered orally. At 3 and 4 hours after nickel intake, disodium EDTA, even in the presence of the standard 5 mg dose of nickel, depressed nickel in plasma significantly below levels during fasting. Concentrations of amino acid in rat brain were unaffected by zinc deficiency Grand Forks, North Dakota. The effect of zinc deprivation for 9 days on concentrations of amino acid in the rat brain was examined. The zinc deficient rats and control group had some differences in concentrations of amino acid and |