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Biomedical subjects

B Lönnerdal

Publications and source records attributed to B Lönnerdal.

At least 163 records · Page 9Linked to original sources

Intrinsic and extrinsic labeling for studies of manganese absorption in humans.

A dual-radioisotope method was used to simultaneously study whole-body manganese retention from a chicken liver based meal intrinsically labeled with 54Mn and extrinsically labeled with 52Mn. Manganese retention was monitored in a sensitive whole-body counter during approximately 30 d in six young adult women. Both radioisotopes were retained to a similar degree and excreted at identical rates. Retention at d 5 was 14.4 +/- 10.3 and 14.0 +/- 9.9% while retention at d 10 was 5.0 +/- 3.1 and 5.0 +/- 3.0% (X +/- SD) for 54Mn and 52Mn, respectively. From these results we conclude that the intrinsic and extrinsic Mn isotopes did form a common pool before absorption. The results can therefore be regarded as a direct validation of the use of extrinsic labeling for studies of Mn retention for estimating Mn absorption in man.

Adult↗

Mineral composition and zinc metabolism in female mice of varying age and reproductive status.

Zinc metabolism of adult female C57BL/6J mice varying in age and reproductive status was studied using 65Zn. Animals were injected intraperitoneally with isotope, and whole-body and tissue turnover of 65Zn was measured. Biological half-life of whole-body 65Zn for pregnant females was 129% of that for nonpregnant, nonlactating females of similar age (25.7 and 20.0 d, respectively). Conversely, the half-life of zinc was less for lactating (11.1 d) and aged (15.3 d) females than for either pregnant or nonpregnant, nonlactating young adult females. Retention of 65Zn was generally lower for all tissues of pregnant and lactating dams than for nonpregnant, nonlactating females except for brain and tibia. In aged females, specific activity at 20 d postinjection did not differ from that of nonpregnant, nonlactating young adult females for any tissue except bone. While specific activity of tibia increased during pregnancy and lactation, it was lower in aged females than in nonpregnant, nonlactating young adult females. Increased organ content of zinc resulted from changes in zinc concentration or in organ mass or both, and was supported by increased food intake. Thus, greater food intake for these groups than for young adult females contributed to the higher turnover of tissue 65Zn. Differences in concentrations of Cu, Ca and Mg were also observed among groups for some tissues; the significance of these differences and their relationship to zinc metabolism are not clear.

Animals↗

Effect of varying dietary zinc intake of weanling mouse pups during recovery from early undernutrition on growth, body composition and composition of gain.

Catch-up growth during recovery from undernutrition is characterized by rapid body weight gain often marked by disproportionately high fat gain. In this study dietary zinc intake of mouse pups during recovery from undernutrition affected composition of gain as well as growth. Mouse pups were undernourished during the suckling period and then fed 25% casein recovery diets containing 5, 10, 40 or 110 micrograms Zn/g diet. Pups given dietary zinc levels of 40 micrograms Zn/g ad libitum achieved recovery body weights and had normal body composition. However, previously undernourished pups given marginal levels of dietary zinc (10 micrograms Zn/g diet) had similar food intakes, similar final body weights, lower lean body mass gains and greater fat gains (males only) than controls. Pups fed low zinc diets (5 micrograms Zn/g diet) were unable to attain recovery body weight and had less protein gain than previously undernourished animals fed higher zinc-containing diets or healthy pups fed the same zinc levels. The results were consistently more pronounced in males. Thus dietary zinc deficiency during catch-up growth after undernutrition limited both recovery and protein gain, whereas marginal dietary zinc intake limited protein gain in mice.

Animals↗

Effect of varying dietary zinc intake of weanling mouse pups during recovery from early undernutrition on tissue mineral concentrations, relative organ weights, hematological variables and muscle composition.

Because growth is an early sign of zinc (Zn) deficiency in young animals, it is often assumed that the occurrence of normal growth indicates adequate Zn status. In an earlier study we found that both marginal (10 micrograms Zn/g) and low (5 micrograms Zn/g) dietary Zn intake resulted in altered composition of gain in mouse pups that had been previously undernourished (L) from d 10 to 21 of suckling and rehabilitated from d 21 to 40 with high protein recovery diets. Therefore we examined several tissues, organs and biochemical measures to identify other variables that might be sensitive to either marginal or low dietary Zn intake in mice. After undernutrition in the suckling animal, liver Zn concentrations were lower; they normalized when the pups were subsequently fed recovery diets irrespective of dietary Zn intake (5-110 micrograms Zn/g). Bone Zn was 30% lower in pups fed low Zn, and 30% higher in pups given Zn-supplemented recovery diets (110 micrograms Zn/g) compared with controls (40 micrograms Zn/g). Thus bone Zn concentration was highly correlated with dietary Zn intake and lower liver Zn was highly correlated with undernutrition. Most organs of L pups recovered in proportion to body weight; the exceptions were brain, kidney and gastrocnemius muscle. At d 21 or 40, brain weight was most conserved and kidney weight was stunted during either protein or Zn deprivation. Gastrocnemius muscle weight in L pups was stunted to a much greater degree than other tissues, although proximate analysis showed muscle composition was similar among groups. These data support previous reports that adequate dietary Zn is essential for optimal recovery from early undernutrition.

Animals↗

Marginal zinc deficiency affects maternal brain microtubule assembly in rats.

The possible physiological role of Zn in tubulin polymerization was studied. Tubulin assembly in vitro was characterized in brain supernatants from rats fed a marginally Zn-deficient diet (10 micrograms Zn/g) during pregnancy and lactation. The initial rate of tubulin polymerization was significantly lower (27%) in brain supernatants from the marginally Zn-deficient animals than from controls. This was associated with a lower Zn concentration in the brain supernatants from the marginally deficient rats. Total protein and tubulin concentrations were the same in the supernatants from both groups. These data show that Zn is necessary for normal tubulin assembly and indicate that one biochemical defect underlying brain alterations in Zn deficiency could be abnormal microtubule function.

Animals↗

Specific binding of lactoferrin to brush-border membrane: ontogeny and effect of glycan chain.

Bioavailability of iron from human milk is exceptionally high. It has been suggested that lactoferrin, the major iron-binding protein in human milk, may participate in this high iron bioavailability from milk. We examined the interaction of lactoferrin with the intestinal brush-border membrane using the rhesus monkey as a model. Brush-border membrane vesicles were prepared from monkeys of various ages. Binding studies with 59Fe-labeled human and monkey lactoferrin were performed to examine interaction of lactoferrin with the brush-border membrane. Specific saturable binding of lactoferrin was found at all ages studied (fetal, suckling infant, weaned infant, juvenile, and adult). The dissociation constant for lactoferrin-receptor binding was 9 X 10(-6) M. In contrast, no binding of serum transferrin or bovine lactoferrin occurred. Removal of fucose from the lactoferrin glycans resulted in a significant decrease in binding. It was concluded that lactoferrin in milk may function in the process of iron absorption through interaction with a small intestinal receptor and that fucosylated glycans on the carbohydrate chain of lactoferrin are necessary for receptor recognition.

Aging↗

Effect of infant cereals on zinc and copper absorption during weaning.

Zinc and copper absorption from five infant cereal products mixed with water, human milk, or cow's milk was measured using an in vivo absorption model (rat pup) involving gastric intubation of extrinsically radiolabeled diets. Whole-body copper 64 uptake, nine hours after intubation, ranged from 14% to 31% of the dose given for the different cereal combinations. The resultant bioavailability of copper from human milk-cereal combinations (23% to 26%) was significantly lower than that from human milk alone (38%). Whole-body zinc 65 uptake, nine hours after intubation, ranged from 13% to 54% of the dose given for the different cereal combinations. These values were significantly lower than the whole-body zinc 65 uptake from milk alone (61%). Zinc availability was lower (13% to 25%) from dry cereal combinations that contained phytic acid (oatmeal and high-protein varieties) compared with the ready-to-serve cereal-fruit combinations (24% to 54%). The highest zinc uptake (37% to 54%) was from rice-fruit combinations that do not contain phytic acid. We estimated the amounts of zinc and copper that would be absorbed from these cereal products and speculated on the potential impact of these foods on the weaning infant's zinc and copper nutriture. Depending on the feeding practices employed during the weaning period, it is apparent that infant cereals may compromise utilization of zinc and copper from milk diets during weaning.

Absorption↗

Zinc and copper in milk and tissues of nursing lethal milk mutant mice.

Zinc concentration was lower in liver of suckling 1-d-old lethal milk (lm/lm) mutant mice than in wild-type pups, in accordance with the hypothesis of milk-induced zinc deficiency previously proposed to underlie this mutation. Despite the initial deficiency, by 3 d of age suckling lm/lm pups exhibited higher levels of hepatic zinc than did lm/lm-nursed wild-type pups. Intestinal zinc and copper concentrations were normal in 1-d-old lm/lm pups, but by 3 d of age were also higher in lm/lm pups than in wild-type pups foster-nursed on lm/lm dams. Contrary to a previous report, we found that zinc concentration in milk of lm/lm dams was not significantly different from those of controls, between 4-20 d postpartum. Mutant milk showed normal zinc distribution as determined by gel-filtration chromatography or by DEAE-cellulose chromatography of zinc-binding ligands derived from EDTA-dissociated micelles, normal copper levels, normal amounts of citrate, a zinc (II) and copper (II)-binding ligand and normal amounts of glutamate, a proposed copper (II)-binding ligand. Total mammary glands and mammary gland cytosols from lm/lm mice exhibited normal zinc concentrations. Copper levels, however, were higher in lm/lm mammary gland cytosols than in controls. These results suggest that an increased uptake and/or retention of zinc and copper in the tissues studied may underlie the signs of zinc deficiency seen in lethal milk mutant mice.

Animals↗

Iron and zinc concentrations and 59Fe retention in developing fetuses of zinc-deficient rats.

Because disturbances in iron metabolism might contribute to the teratogenicity of zinc deficiency, we examined the effect of zinc deficiency on fetal iron accumulation and maternal and fetal retention of 59Fe. Pregnant rats were fed from mating a purified diet containing 0.5, 4.5 or 100 micrograms Zn/g. Laparotomies were performed on d 12, 16, 19 and 21 of gestation. Maternal blood and concepti were analyzed for zinc and iron. Additional groups of dams fed 0.5 or 100 micrograms Zn/g diet were gavaged on d 19 with a diet containing 59Fe. Six hours later maternal blood and tissues, fetuses and placentas were counted for 59Fe. Maternal plasma zinc, but not iron, concentration was affected by zinc deficiency on d 12. Embryo zinc concentration on d 12 increased with increasing maternal dietary zinc, whereas iron concentration was not different among groups. On d 16-21 plasma iron was higher in dams fed 0.5 micrograms Zn/g diet than in those fed 4.5 or 100 micrograms/g, whereas plasma zinc was lower in dams fed 0.5 or 4.5 micrograms Zn/g than in those fed 100 micrograms Zn/g diet. On d 19 zinc concentration in fetuses from dams fed 0.5 micrograms/g zinc was not different from that of those fed 4.5 micrograms/g zinc, and iron concentration was higher in the 0.5 microgram Zn/g diet group. The increase in iron concentration in zinc-deficient fetuses thus occurs too late to be involved in major structural teratogenesis. Although whole blood concentration of 59Fe was not different in zinc-deficient and control dams, zinc-deficient dams had more 59Fe in the plasma fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

The effect of varying dietary zinc levels on the concentration and localization of zinc in rat bile-pancreatic fluid.

To determine if zinc homeostasis occurs by zinc output from bile-pancreatic secretions, the bile-pancreatic duct and intestine of rats were surgically cannulated, and bile-pancreatic fluid was collected 2 h/d from the day of surgery to 8 d after surgery. The rats were fed diets containing 10, 100 or 1000 micrograms Zn/g diet before and after surgery. The effect of surgery itself was significant; food intake was initially lower than presurgery levels, but returned to presurgery levels by d 5. Protein and zinc concentrations, and carboxypeptidase A (CpA) and carboxypeptidase B (CpB) activities in bile-pancreatic fluid increased after surgery and leveled off at approximately d 6. Among the dietary zinc groups, the concentration of zinc in bile-pancreatic fluid varied significantly, whereas concentrations of calcium and copper did not. Zinc concentration in bile-pancreatic fluid for d 1-8 postsurgery averaged 1.8, 3.2 and 4.4 micrograms Zn/g, in the groups fed 10, 100 and 1000 micrograms Zn/g diet, respectively. Because the percent of zinc ingested that was secreted in bile-pancreatic fluid, estimated to be 57, 9.5 and 1.2% for the groups consuming the diets containing 10, 100 and 1000 micrograms Zn/g diet respectively, was not similar in the three groups, the quantity of zinc in bile-pancreatic fluid is not proportionally related to the amount of zinc ingested. Our results therefore suggest that zinc secretion in bile-pancreatic fluid does not play a major role in zinc homeostasis. Molecular localization of zinc in bile-pancreatic fluid and measurement of activity of CpA and CpB indicated that zinc in bile-pancreatic fluid is associated primarily with these digestive enzymes.

Animals↗

Maternal sodium intake does not affect postprandial sodium concentrations in human milk.

Sodium concentration in human milk is known to vary diurnally and throughout lactation. To investigate potential postprandial variation, eight exclusively breast-feeding mothers of infants 10-19 wk of age were visited on two different days after a 3-h fast. On one day, they were fed a low sodium lunch (130 mg), and on the other, the same lunch with a high sodium content (2175 mg). Milk samples were collected before each lunch and breasts were emptied with an electric pump. After lunch, samples were collected from each breast every 15 min for 2 h. No significant postprandial variation was found in mean sodium or potassium concentrations, nor were significant differences found in sodium or potassium values after the high sodium or the low sodium lunch. We conclude that there is no significant influence of maternal sodium intake on postprandial milk sodium or potassium concentrations.

Adult↗

Compartmentalization and quantitation of protein in human milk.

Human milk protein was determined by three colorimetric methods and by Kjeldahl analysis. The distribution of nitrogen (N) and protein was determined within various milk compartments. Total N, whey, casein, nonprotein nitrogen (NPN), cell N and N in the fat fraction were analyzed by micro-Kjeldahl analysis after a series of centrifugation and ultracentrifugation separations. Fresh milk samples (colostrum, transitional milk and mature milk) were centrifuged at 500 X g to separate milk cells and at 5000 X g to skim the milk. Decelled milk and skimmed milk were ultracentrifuged at 189,000 X g to separate fat and casein micelles from whey. NPN was analyzed after trichloroacetic acid precipitation. Whole milk, decelled milk, skimmed milk and whey were analyzed for protein with the Lowry method, modified for fat-containing samples, the Bradford dye-binding assay (Bio-Rad) and the Pierce bicinchoninic acid (BCA) assay. Cell nitrogen had a tendency to be lower in mature milk than in colostrum. Colostrum contained only 6% casein protein, whereas mature milk contained 13%. Fat from skimming was lower in N than fat from ultracentrifugation. Average NPN levels were similar for milk from all three lactation periods, and constituted 10% of colostrum N and 25% of mature milk N. Protein determined by the Bio-Rad method on whole milk samples had the lowest variability (square root MSE) when correlated to Kjeldahl values. All three assays had lower variability when analyzing whey and skimmed milk than when analyzing whole milk. The Lowry method and the Bio-Rad method had low variability for whey and skimmed milk samples, but the Lowry method yielded analytical values closest to Kjeldahl protein values. The BCA method consistently overestimated Kjeldahl protein by 30%.

Caseins↗

Persistence of human milk proteins in the breast-fed infant.

Several proteins in human milk are postulated to have physiological functions in the breast-fed infant. Therefore, survival of human milk proteins after passage through the gastrointestinal tract of the breast-fed infant was investigated. Fecal samples were collected from exclusively breast-fed term infants and milk samples from their mothers. Soluble proteins in the feces were extracted and analyzed for total protein, nitrogen, lactoferrin, secretory IgA, serum albumin and lysozyme. Significant amounts of lactoferrin and secretory IgA were excreted by the infants and this excretion decreased throughout the study period in a trend similar to the decreasing milk concentrations of these proteins. Gel filtration demonstrated excreted lactoferrin and secretory IgA to be intact. No serum albumin or lysozyme was detected in the fecal extracts. Crossed immunoelectrophoresis showed three human milk proteins to be present in the feces--the third was identified as alpha 1-antitrypsin. Excretion of these proteins indicates the total protein content of human milk is an over-estimation of the protein nutritionally available to the infant.

Breast Feeding↗

Analysis of whole blood manganese by flameless atomic absorption spectrophotometry and its use as an indicator of manganese status in animals.

To investigate the use of whole blood manganese (Mn) as an indicator of total body Mn, we measured Mn in whole blood and liver of rats fed purified diets containing adequate (45 micrograms Mn/g diet) or deficient (1 microgram Mn/g diet) Mn. The mean hepatic Mn concentration was significantly lower (P less than 0.001) in the Mn-deficient group compared to the control group, 0.36, microgram Mn/g and 1.73 micrograms Mn/g, respectively. Furthermore, whole blood Mn was significantly reduced (P less than 0.001) in the deficient group when compared to the control group, 4.0 ng Mn/ml and 8.6 ng Mn/ml, respectively. Hepatic Mn linearly regressed against whole blood Mn yielded a statistically significant (P less than 0.001) correlation coefficient of 0.775. These data suggest that whole blood Mn is a valid indicator of body Mn status and thus may be useful, in addition to the measurements of serum copper and zinc, for the diagnosis and prognosis of diseases in which the metabolism of trace elements is affected. In addition, this paper describes and delineates operational parameters for the measurement of whole blood Mn using the IL 551 atomic absorption spectrophotometer and the IL 555 B flameless atomizer.

Animals↗

Similar effects of zinc deficiency and restricted feeding on plasma lipids and lipoproteins in rats.

The objective of this study was to determine whether alterations in HDL composition observed previously were due specifically to zinc deficiency or to reduction in food intake. Rats were placed into three groups and fed for 21 d a zinc-adequate diet (100 ppm) ad libitum, or a zinc-deficient diet (less than 1 ppm) ad libitum, or the zinc-adequate diet at an intake equal to that of the deficient group. Blood plasma was fractionated into VLDL, LDL and HDL fractions, and plasma and the isolated fractions were analyzed for lipids and apolipoprotein composition. Analysis of plasma and liver zinc indicated that animals consuming the low zinc diet were deficient. Zinc deficiency and restricted feeding were associated with lower plasma and VLDL triglyceride levels and lower HDL cholesterol levels. The similarities in overall pattern of lipoprotein composition between the zinc-deficient and restricted-intake groups indicate that reduction in food intake may account for the differences in lipoprotein composition which were observed.

Animals↗

Release of zinc from maternal tissues during zinc deficiency or simultaneous zinc and calcium deficiency in the pregnant rat.

Earlier studies have shown that diets that increase tissue catabolism reduce the teratogenic effects of zinc deficiency. The hypothesis that zinc may be released from body tissues when the metabolic state is altered was further tested. Nonpregnant Sprague-Dawley females were injected with 65Zn; after equilibration, the two major pools of zinc, bone and muscle had different specific activities, muscle being much higher. Females were mated and fed diets adequate in zinc and calcium, deficient in zinc alone or deficient in both zinc and calcium. Calculations using weight loss, zinc content of maternal bone and muscle and total zinc content of the fetus at term indicated that most of the zinc in the fetus at term in both the zinc-deficient and zinc-calcium-deficient groups came from breakdown of maternal muscle in the last 3 d of pregnancy. The relatively small amount of additional zinc released from bone in the zinc-calcium-deficient rats early in pregnancy was sufficient to prevent abnormal organogenesis. Specific activity of zinc in the zinc-deficient and zinc-calcium-deficient fetuses was equal and high, indicating that most zinc in these fetuses came from maternal tissues and from the same maternal sources in both groups. In contrast, specific activity of zinc in the fetuses from rats fed adequate zinc and calcium was less than 30% of that in either of the deficient groups; this is consistent with the hypothesis that most zinc accrued by these fetuses came directly from the diet.

Animals↗

The effect of age on manganese uptake and retention from milk and infant formulas in rats.

Manganese nutrition of the neonate is poorly understood, due in part to a paucity of information on the amount and availability of manganese in infant foods. We have developed a suckling pup model to assess the uptake of manganese from fluid diets by using extrinsic labeling. Human milk, cow milk and infant formulas were fed by intubation to fasted rat pups and adults. Rats were killed after varying time periods, and tissues were removed and counted. A period of 6 h was found to be adequate to allow for stomach emptying while limiting tissue redistribution; 24 h was found to reflect pup manganese retention. From human milk, manganese retention was highest (greater than or equal to 80%) in pups less than or equal to 15 days of age; in older pups average retention decreased to 40%. Using d 14 pups to assess relative Mn uptake from diets, wholebody Mn uptake was highest from cow milk (approximately 89%); uptake from human and cow milk formula was similar (approximately 80%) whereas it was lower from soy formula (approximately 60%). These findings suggest that bioavailability of Mn from infant diets is very high during the suckling period. Since most formulas contain considerably more manganese than is found in human milk, Mn deficiency may be less of a concern than possible toxicity from formulas.

Absorption↗