Biomedical subjects
M R Fox
Publications and source records attributed to M R Fox.
Preparation of inositol phosphates from sodium phytate by enzymatic and nonenzymatic hydrolysis.
Procedures for preparing myo-inositol bis-, tris-, tetrakis-, and pentakisphosphates from sodium phytate were established. Hydrolysis was achieved by autoclaving or enzymatic treatment; the inositol phosphates were separated by anion-exchange chromatography and were identified by fast atom bombardment-mass spectrometry. Enzymatic hydrolysis was more specific than autoclaving for isomer formation, whereas autoclaving was more efficient for producing the bis- and trisphosphates, which did not accumulate in significant amounts under the conditions of enzymatic hydrolysis. Sodium salts of the inositol phosphates were more powdery and less hygroscopic than the potassium salts. The procedures were satisfactory for producing gram quantities of each inositol phosphate, amounts adequate for animal studies of effects on mineral bioavailability.
Dietary model for production of experimental zinc deficiency in man.
A semipurified diet based on soy protein was developed to induce mild zinc deficiency in five male volunteers. Each of seven daily menus provided (mean +/- SD) 2248 +/- 128 kcal, 56.6 +/- 5.7 protein, 261 +/- 30 g carbohydrate, 110 +/- 21 g fat, 8.5 +/- 1.4 g fiber, and 4.8 +/- 1.3 mg zinc. The analytical value for phytate:zinc molar ratio was 21 +/- 9. One subject, who received five of the menus for 28 wk, lost approximately 200 mg body zinc and 7% weight; zinc concentration declined 25% in plasma, 30% in lymphocytes, and 55% in neutrophils. This dietary model allowed simple formulation of new menus for subjects in diverse states of health. It caused no ill effects after prolonged consumption, and all deficiency symptoms were reversed by zinc supplementation of 30 mg/d for 20 wk. With simple manipulation, this dietary model may be used safely for gradual induction of zinc and/or other micronutrient deficiencies in humans.
Assessment of cadmium, lead and vanadium status of large animals as related to the human food chain.
Cadmium (Cd) and lead (Pb) are of established toxicological significance for humans, and it is important that intakes from foods not cause excessive exposure. Both elements concentrate to high levels in liver and kidneys of large, domestic food animals (cattle, sheep and swine), and Pb also concentrates in bone, which is sometimes used in the form of bone meal as a dietary supplement. Milk is a significant source of Cd and Pb for infants and toddlers. Levels of these elements in domestic food animal tissues and milk are presently within acceptable ranges for human consumption. Vanadium (V) sources to animals may increase and create potential human food problems; however, at the present time meats and milk are safe to consume with respect to this element.
Purified reference diets for weanling rats: effects of biotin and cellulose.
Standardized purified diets limited to required nutrients are needed for nutritional and toxicological studies. In the present study, we formulated a biotin- and cellulose-free diet of reproducible mineral composition (diet A), based on diet AIN-76, and fed it to weanling Long-Evans rats for 3 wk. Inductively coupled argon plasma atomic emission spectrometry was used to determine Ca, Cu, Fe, K, Mg, Mn, Na, P and Zn in liver, duodenum, kidney, spleen and femur. Results were compared with those obtained with rats fed biotin- and/or cellulose-supplemented variations of diet A, diet AIN-76 and diet NIH-31 (an open-formula stock diet). Weanling rats grew slowly and steadily on purified diet A. Growth rates increased when diet A was supplemented with biotin and cellulose. In general, differences among tissue mineral levels in rats fed diet NIH-31 and those fed diet AIN-76 were more pronounced than those among groups fed our purified diets. Values for hemoglobin and hematocrit were significantly lower in rats fed all purified diets than in those fed diet NIH-31. Diets A + biotin, A + cellulose and A + cellulose + biotin appear satisfactory as reference diets for measuring mineral interactions at near-requirement levels as well as effects of fiber on mineral utilization or for studies on vitamins whose endogenous synthesis may be influenced by dietary fiber.
Effects of low levels of dietary lead and iron on hepatic RNA, protein, and minerals in young Japanese quail.
Day-old Japanese quail were fed purified diets containing either 0.2 (control), 5.4, or 16.2 ppm lead as the acetate with either 25 (deficient) or 100 ppm (adequate control) iron for 2 weeks. Iron deficiency caused decreases in hemoglobin, iron, and manganese in the liver, and hepatic RNA synthesis. Iron deficiency also caused increased concentrations of lead, calcium, and molybdenum in the liver. Lead supplements caused increased concentrations of lead in the liver, and with adequate dietary iron, each supplemental lead level caused a slight decrease in the concentration of RNA in the liver. Treatment had no effect on DNA or protein synthesis, body weight, or liver weight in relation to body weight. These low levels of dietary lead did not cause the same adverse metabolic effects observed by others with higher levels of lead; however, iron deficiency increased lead uptake by the liver and affected RNA synthesis.
Trace element studies in weanling rats: maternal diets and baseline tissue mineral values.
The initial nutritional status of experimental animals can influence their response to subsequent dietary regimens. In the present study, we determined the variations in minerals in diet NIH-31, a breeding colony stock diet, and in tissues of weanling rats nursed by dams fed this diet. Inductively coupled plasma-atomic emission spectrometry (ICP-AES) was used to determine nine elements (Ca, Cu, Fe, K, Mg, Mn, Na, P and Zn) in diet and in liver, kidney, spleen, duodenum and femur from 22- to 26-day-old rats. Wet digestions were performed in mixtures of nitric, perchloric, and sulfuric acids (diets and soft tissues) or nitric and perchloric acids (femur). Solution concentrations ranged from less than 25 ng/ml for the trace elements to greater than 100 micrograms/ml for the major elements. Large variations in mineral content were found between batches of commercially prepared NIH-31 diet; relative amounts of Cu, Fe, Mn and Zn varied markedly. Significant differences in concentrations of major and trace minerals in liver, kidney, spleen and duodenal tissue were found among groups of weanling rats obtained from the same supplier at different times. Mn was readily quantitated in all tissues except spleen, where it was below detection limits. The precision obtained with the ICP-AES methodology has significant advantages for establishing variations in tissue mineral levels.
Effects of zinc, iron and copper deficiencies on cadmium in tissues of Japanese quail.
Experiments with young Japanese quail were conducted to determine whether combined moderate deficiencies of zinc, iron and copper would cause greater uptake and tissue retention of cadmium than the single deficiencies. Birds were fed the experimental diets containing 62 ppb cadmium from hatching to 16 days of age. On day 9 each bird received a dose of 109CdCl2 in its diet. On day 10, the duodenal and jejunal-ileal tissues contained large amounts of cadmium, and there were many significant effects of treatment on cadmium-109 retention in the livers and kidneys. At day 16, zinc deficiency caused increased cadmium in the liver, whereas iron and copper deficiencies each caused increased cadmium in the kidneys. Combined deficiencies had little or no greater effect than single deficiencies and in some cases the combined effect was less than that of a single deficiency.
Magnesium stores and anemia in young Japanese quail.
Studies were conducted to determine the effect of age on magnesium requirement and whether high dietary magnesium during the first 7 days of life would protect against subsequent magnesium deficiency. Day-old Japanese quail were fed a casein-gelatin diet containing either 300 (requirement) or 600 ppm Mg. Beginning on day 7, half of the birds in each group received either 160 (deficient) or 300 ppm Mg. In birds fed the requirement level during week 1 followed by the deficient diet, hemoglobin decreased on day 10, reaching the lowest value on day 14. Other adverse effects included mortality; slightly reduced growth rate; elevated iron in the liver, spleen, and tibia; decreased tibia magnesium; and increased spleen weight. Higher dietary magnesium (600 ppm) during week 1 prevented deficiency when 160 ppm Mg was fed in week 2; however, tibia magnesium was lower than that in birds fed 300 ppm Mg throughout. The protection may be related to reutilization of skeletal magnesium, which was elevated on day 7. In this and another experiment, birds initially fed 300 ppm Mg followed by 160 ppm (7-28 days) or 125 ppm Mg (14-28 days) had normal hemoglobin values at 21 and 28 days. These experiments showed that magnesium requirement decreased as quail aged (up to 4 weeks) and that a high magnesium diet (600 ppm) fed through days 0-7 protected against subsequent dietary inadequacy.
Effects of dietary zinc, manganese, and copper on tissue accumulation of cadmium by Japanese quail.
The beneficial effects of a combined dietary supplement of Zn, Cu, and Mn in decreasing Cd absorption was previously reported. The purpose of this study was to investigate the individual and combined effects of these three elements. In the first two experiments, day-old Japanese quail were fed basal diets containing either requirement amounts of Zn (30 ppm) and Mn (12 ppm) and slightly above requirement levels of Cu (5 ppm). From Day 7 birds were fed either the basal diet or diets containing combinations at twice these concentrations; a 2 X 2 X 2 factorial design was used. 109Cd content and Cd concentration of these diets were 100 mu Ci and 145 micrograms/kg, respectively. In the third experiment, day-old birds were fed either the basal diet or a basal diet containing 109Cd and single additional supplements of either Zn, Cu, or Mn. All birds were killed at 14 days of age. The Cd concentration was determined for the duodenum, jejunum-ileum, liver, and kidney. When the experimental diets were fed for 7 days, only Zn had a protective effect against Cd. Whereas none of the elements reduced the Cd concentration of the duodenum, Zn reduced the Cd in the jejunum-ileum, liver, and kidney by approximately 66, 21, and 11%, respectively. Cu and Mn caused occasional increases of Cd in some tissues. Feeding the experimental diets for 2 weeks resulted in similar responses. Zn nutrition appears to play an important role in protecting against dietary Cd absorption.
Effects of dietary mineral levels on metabolism and requirements.
Currently, 26 mineral elements are considered important for humans; these include essential trace and macro elements, two that may be required, and others of concern solely for their toxic properties. Almost all elements are toxic at high intakes, and excessive consumption of dietary mineral supplements is a source of potential hazard in addition to environmental and industrial sources of exposure. In assessing requirements and the health effects of variations in dietary mineral levels, the tissue concentrations of the elements can be very useful. The interpretation of tissue mineral levels is tempered by factors that may influence the metabolism of the element of concern as well as by the correlations of intake and tissue levels with physiological effects. For elements that have been studied most extensively and for which reliable analytical methods exist, a multiplicity of interactions have been shown. The practical significance of these interactions for humans is an area of active research. With reliable analytical methods for additional elements, it is anticipated that important advances will be made relative to those chemical elements and their action both as nutrients and as toxicants.
Cadmium bioavailability.
Cadmium slowly accumulates in the liver and kidney and has a long biological half-life, estimated to be 2-3 decades in the kidney. If the kidney cadmium concentration reaches a critically high level, proximal tubular damage results, which can be followed by severe bone mineral loss. There are only a few measurements of cadmium bioavailability in foods; however, the data are indicative of lower utilization from foods than from inorganic salts. In animal tissues cadmium is bound primarily to a heat-resistant small protein with a high cysteine content (metallothionein), whereas little is known about the form in which cadmium occurs in the edible parts of plants. Low intakes of many nutrients exacerbate the effects of cadmium and supplemental intakes are protective. Newborn and young animals absorb much higher quantities of cadmium than adults. There is some evidence in animals that females may be more adversely affected than males. Itai-itai disease, a painful disease with kidney damage and bone demineralization, occurred in elderly Japanese women who had borne several children and who were exposed to cadmium via food and drinking water. Inasmuch as cadmium in the U.S. food supply affords an estimated safety factor of only 4- to 15-fold, it is important to establish factors that affect the bioavailability of cadmium from foods.
Bioavailability of lead in oysters fed to young Japanese Quail.
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Faculty development activities.
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Mineral content of human tissues from a nutrition perspective.
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Effects of vitamin C and iron and cadmium metabolism.
Toxic levels of dietary cadmium (5-200 ppm) interfered with iron absorption and produced an iron deficiency. Supplements of iron (particularly the divalent form) and ascorbic acid protected against the cadmium. With very low levels of dietary cadmium (about 0.06-0.08 ppm), typical of those in the diets of humans, supplements of iron(II) and ascorbic acid markedly decreased cadmium concentrations in the liver, kidney, and small intestine. Iron deficiency changed the distribution of cadmium within the body. The effect of ascorbic acid on cadmium metabolism appears to depend primarily, if not entirely, on its influence in improving iron absorption. Maintenance of modest iron stores appears to be very important in minimizing cadmium absorption.
Safe levels of cadmium in intravenous diets.
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Effects of nutritional factors on metabolism of dietary cadmium at levels similar to those of man.
Several nutrients are known to affect cadmium toxicity, but little is known about the effect of dietary nutrient levels on absorption and tissue retention of cadmium at low dietary levels, similar to those of man. Feeding gradedlevels of zinc in a casein-gelatin diet to young Japanese quail with 109Cd (as the chloride) and 0.062 ppm added cadmium decreased the cadmium concentrations in the proventriculus-ventriculus, duodenum, jejunum-ileum, and the liver, but not in the kidney. Zinc also affected some zinc, iron, manganese, and copper tissue levels. Different tissue concentration patterns of cadmium and essential minerals were obtained with two purified control diets, one based on casein-gelatin and the other on soy isolate as the principal protein sources. The data show that relatively small dietary changes can markedly affect tissue levels of cadmium and that a low intake of zinc may increase the risk to dietary cadmium exposure. The complexity of the nutrient interrelationships and their effects on cadmium require further study to define mechanisms, which may be similar to those produced by low cadmium intakes in man.