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Biomedical subjects

B Lönnerdal

Publications and source records attributed to B Lönnerdal.

At least 127 records · Page 7Linked to original sources
PubMed1990

Relationship of milk iron and the changing concentration of mammary tissue transferrin receptors during the course of lactation.

The concentration of iron in all mammalian milks falls during lactation while the infant's iron requirement increases. Little is known, however, about the entry of iron into milk. Recently, transferrin receptors have been identified on lactating rat mammary plasma membranes, which may regulate iron entry into mammary tissue, potentiating its availability for subsequent transport into milk. This study was conducted to determine what relationship exists between the declining concentration of milk iron and the transferrin receptor concentration during various stages of lactation. Minimal transferrin receptors were detected in nulliparous rats. Total mammary transferrin receptor content increased during early and mid-lactation while milk iron concentration decreased. The continued appearance of high levels of transferrin receptors throughout lactation, without a concomitant increase in milk iron concentration, suggests a need for iron for functions other than cellular growth or secretion into milk to meet infant needs.

Journal Article↗
PubMed1990

Characterization of transferrin receptors on plasma membranes of lactating rat mammary tissue.

Little is known about the transport of iron into the mammary secretory cell and the process of milk iron secretion. The concentration of iron in milk is remarkably unaffected by maternal iron status, suggesting that the uptake of iron into the mammary gland is regulated. It is known that iron enters other cells via transferrin receptor-mediated endocytosis. This study was designed to isolate and characterize the mammary gland transferrin receptor in lactating rat mammary tissue using immunochemical techniques. The existence of functional mammary gland transferrin receptors in lactating rodents was demonstrated using radiolabel-binding techniques. Isolation of mammary transferrin receptors by affinity chromatography was confirmed using immunoelectrophoresis and slot blot analysis. The intact transferrin receptor was found to have a molecular weight of 176 kd as determined by Western blotting followed by scanning densitometry. Reduction of the receptor with beta-mercaptoethanol gave a molecular weight of 98 kd. An additional immunoreactive band of 135 kd was observed. The presence of transferrin receptors in normal lactating rat mammary tissue is likely to explain iron transport into mammary tissue for both cellular metabolism and milk iron secretion.

Journal Article↗
PubMed1990

Human-milk proteins: analysis of casein and casein subunits by anion-exchange chromatography, gel electrophoresis, and specific staining methods.

Casein in human milk is believed to serve several biological functions in newborns. However, the content and subunit composition of human casein has so far received little attention. We recently developed a method to separate human-milk whey and casein by adjustment of whole human milk to pH 4.3 and addition of calcium followed by ultracentrifugation. In this study we analyzed and evaluated human casein prepared by different methods. We used fast protein liquid chromatography (FPLC) with an anion-exchange column (Mono-Q) and polyacrylamide gradient gel electrophoresis techniques to analyze the casein subunit composition. Total casein in human milk, as determined by the Kjeldahl method, varies during lactation; the casein content is approximately 20% of the total protein content in early lactation and 45% in late lactation. We found differences in both glycosylation and phosphorylation patterns of kappa-caseins and beta-caseins from premature and term milk samples.

Caseins↗
PubMed1990

Response of rat mammary gland transferrin receptors to maternal dietary iron during pregnancy and lactation.

Mammalian milk iron (MFe) concentration decreases during lactation. In human attempts to increase MFe through supplementing the mother with iron during lactation have failed and no correlation between maternal iron status or intake and MFe has been determined, suggesting a regulatory mechanism. In contrast MFe in lactating rats can be affected by very high or low amounts of ingested iron. We previously described a transferrin receptor (TfR) mechanism that controls iron entry into rat mammary tissue. In this study lactating rats were used to determine effects of varying dietary iron during gestation and lactation on mammary TfR and MFe. Dams fed low-iron diets had a small increase in TfR, lower hematological indices (p less than 0.005), and lower MFe (p less than 0.005) than did controls or dams fed high iron. Dams fed the high-iron diet had a significant increase in TfR without a concomitant increase in MFe. There was no correlation between MFe and TfR. These findings suggest that control of MFe lies after iron entry into mammary tissue.

Animals↗
PubMed1990

Altered lactational performance in rats fed low carbohydrate diets and its effect on growth of neonatal rat pups.

The possibility that low carbohydrate diets fed to nursing rat dams altered milk composition and impaired neonatal growth and development was explored. Pregnant control dams fed a 62% glucose diet were paired at parturition with experimental dams fed diets with either severe (0% glucose) or moderate (6% glucose) carbohydrate restriction. At birth half of the littermates of each pair were cross-fostered so that each dam nursed a litter consisting of one-half deficient and one-half control pups. All pups born to dams fed the 0% glucose diet died within 24 h of birth whether they were nursed by control or deficient dams. Control pups cross-fostered to these deficient dams died by the second day; the 0% glucose diet failed to support milk production. In contrast, the dams fed the 6% glucose diet produced milk, but its composition was significantly lower in carbohydrate and lipid than was milk of control dams. This altered milk composition was associated with retarded postnatal growth and development. Control pups cross-fostered to 6% glucose dams showed decreased survival (83% vs. 97%) and significantly reduced body weight (10 g vs. 12 g) at d 7. Conversely, 6% glucose pups cross-fostered to control dams showed improved survival (54% vs. 29%) and significantly increased body weight (9 g vs. 7 g) at d 7. These data showed that carbohydrate-restricted diets altered milk production and/or composition, which, in turn, reduced growth and increased mortality in the pups nursed by dams fed these diets. The results demonstrate that an adequate source of dietary carbohydrate is important for optimal lactational performance.

Animals↗
PubMed1990

Casein and casein subunits in preterm milk, colostrum, and mature human milk.

Human milk proteins have both nutritional and physiological roles for the breast-fed infant. While the biochemistry and developmental patterns for many whey proteins are well known, our knowledge of human casein and its subunits is still limited. We have recently developed a method to isolate casein from whey proteins in human milk and to separate the casein subunits by fast protein liquid chromatography. In this study we have applied this methodology to study the casein subunit pattern in preterm milk, colostrum, and mature milk. Casein concentration increased with lactation time, largely due to an increase in glycosylated forms of casein (kappa-caseins). Thus, the relative proportion of beta-casein to kappa-casein decreased during the lactation period. The patterns of phosphorylated and glycosylated casein subunits were found to vary during lactation, showing that both synthesis and posttranslational modification of beta- and kappa-casein are regulated by different mechanisms.

Adult↗
PubMed1990

Bioavailability of urea nitrogen for the low birthweight infant.

Previous studies have demonstrated increased retention (40%) of dietary urea nitrogen by term infants recovering from infection compared to healthy infants (13%), possibly due to a higher requirement for nitrogen. Since low birthweight infants also have a high requirement for nitrogen, the bioavailability of urea nitrogen was investigated in low birthweight infants using 15N,15N-urea. Four low birthweight infants (gestational age = 30 +/- 2.2 weeks [mean +/- SD], birthweight = 1.4 +/- 0.3 kg) were fed formula enriched with 15N,15N-urea. Metabolic balance studies (72 hours) were performed with urine and fecal collections. Nitrogen was quantitated by Kjeldahl analysis and 15N,15N-urea by gas chromatography/mass spectrometry. Mean nitrogen intake was 489 +/- 32 mg/kg/d, with 75% nitrogen absorption and 62% nitrogen retention. Maximum urinary enrichment was 8%. Cumulative 15N,15N-urea excretion was 72%, resulting in 28% retention. Thus the bioavailability of urea nitrogen for low birthweight infants appears to be intermediate between compromised and normal term infants.

Biological Availability↗
PubMed1990

Fecal alpha 1-antitrypsin in breast-fed infants is derived from human milk and is not indicative of enteric protein loss.

Alpha 1-antitrypsin is a serum protein commonly used as a marker of enteric protein loss. In this study, we have quantified alpha 1-antitrypsin concentration in human milk and its excretion by healthy term breast-fed infants. We found high concentrations of alpha 1-antitrypsin in early milk (0.3-0.6 mg/ml during the first week of lactation) while the concentration fell during subsequent weeks, being detectable through at least 3-4 months of lactation. Significant quantities of intact alpha 1-antitrypsin were found to be excreted by the breast-fed infants studied. The amount excreted was typically higher in early weeks (as much as 200 mg/24 h) and decreased with infant age, possibly due to both decreased intake from the milk as well as increased digestion of the protein by the maturing infant. In vitro studies demonstrated that the trypsin-alpha 1-antitrypsin complex resisted proteolysis by pepsin and pancreatic enzymes; thus, alpha 1-antitrypsin in milk can escape gastrointestinal degradation. We conclude that alpha 1-antitrypsin is not a suitable marker for intestinal protein loss by term breast-fed infants.

Breast Feeding↗
PubMed1990

Effects of formula protein level and ratio on infant growth, plasma amino acids and serum trace elements. I. Cow's milk formula.

The optimum level and ratios of protein to be used in cow's milk formula has recently been under discussion. Healthy term infants were fed from birth exclusively human milk or a formula that varied in protein level or whey: casein ratio: (A) 1.4 g/dl; 55:45, (B) 1.5 g/dl; 55:45, (C) 1.3 g/dl; 55:45, (D) 1.4 g/dl; 60:40, (E) 1.4 g/dl; 20:80. Infants were followed for 12 weeks and blood samples were taken at 2, 4, 8 and 12 weeks. Anthropometric indices did not show any significant differences among groups. Plasma amino acid and BUN levels of the C group were closest to the breast-fed group, while the formula with the highest protein level (B) resulted in high values for some amino acids. When comparing the formulas with 1.4 g protein/dl, the high casein group had the lowest plasma tryptophan levels. Taurine was added to all formulas at a level similar to that of breast milk; plasma taurine levels were similar for all groups. All formulas contained 0.7 mg iron and 0.7 mg zinc/dl; no differences were found among the groups in hematological indices or serum trace elements. These data show that feeding a formula with 1.3 g protein/dl and 55:45 whey: casein ratio from birth will result in growth and metabolic indices similar to those of breast-fed infants, although some plasma amino acid levels are not identical, 1990.

Amino Acids↗
PubMed1990

Effects of formula protein level and ratio on infant growth, plasma amino acids and serum trace elements. II. Follow-up formula.

Infants, that had been formula-fed from birth, were fed follow-up formula with 1.5, 2.2 or 2.9 g protein/dl together with 25 g of cereal/day as supplemental food, or formula only (15 g/dl). Formulas were started at 4 months of age and daily intake, anthropometric measurements and plasma samples taken at 5, 6 and 7 months. Protein intake was 2.0, 3.0 and 3.7 g/kg/d, respectively. Growth data were similar for all groups, as were hemoglobin and serum protein values. BUN values for the group fed only formula with 1.5 g protein/dl were lower than for the group fed the same formula with cereals and the other groups. Plasma amino acids were not affected by the addition of the small amount of cereals to the formula with 1.5 g protein/dl, but significantly higher levels of valine, leucine and histidine were found at 7 months for infants fed the two higher protein levels. The highest protein level also appeared to have a negative effect on plasma zinc levels. These results suggest that a protein level of 1.5 g/dl in follow-up formula (2.0 g/kg/d) is adequate during 4 to 7 months of age and that higher protein levels may be excessive.

Amino Acids↗
PubMed1990

Iron uptake from transferrin and lactoferrin by rat intestinal brush-border membrane vesicles.

Interaction of 59Fe-labeled rat transferrin, human lactoferrin, and bovine lactoferrin with rat small intestinal brush-border membrane vesicles was investigated with the use of a rapid filtration technique. Specific binding of 59Fe-labeled rat transferrin and bovine lactoferrin to brush-border membrane vesicles from suckling and adult rats was identified. In contrast, no binding of human lactoferrin occurred. The presence of transferrin receptors on the brush-border membrane of suckling rats was confirmed by immunoblotting, and the molecular mass of the receptor was 96 kDa under nonreducing conditions. Scatchard plot analysis indicated 2.4 x 10(14) binding sites/mg of membrane protein with an affinity constant (Ka) of 4.9 x 10(6) M-1 for rat milk transferrin and 2.2 x 10(14) binding sites/mg of membrane protein with a Ka of 3.2 x 10(6) M-1 for bovine lactoferrin. Bovine lactoferrin competitively inhibited the binding of rat transferrin to the brush-border membrane vesicles. Deglycosylation of rat transferrin and bovine lactoferrin had no influence on the binding of these proteins. The results suggested that bovine lactoferrin bound to the receptor for rat transferrin on the brush-border membrane and that the polypeptide chain rather than the glycan moiety is responsible for the interaction of these proteins with the rat brush-border membrane.

Aging↗
PubMed1990

Iron retention from lactoferrin-supplemented formulas in infant rhesus monkeys.

Iron absorption from human milk and infant formula has received much attention, but experimental design problems have been common. In our study, iron retention from human milk, milk-based infant formula (IF) with and without supplemental ferrous sulfate, and IF supplemented with either human or bovine lactoferrin (Lf) was evaluated in infant rhesus monkeys. The exchange of 59Fe (III) Cl3 between the whey, casein, and fat fractions required up to 72 h to reach the same distribution as intrinsic iron, depending on the type of diet. Infant monkeys were intubated with labeled human milk or IF and counted in a whole body counter. Each infant received all five diets and was also intubated with a reference dose of 55Fe (II) ascorbate. There was no significant difference in iron retention (mean +/- SEM) from the experimental diets: human milk 32.5 +/- 5.1%; IF 32.1 +/- 8.0%; IF + Fe 23.0 +/- 3.9%; IF + human Lf 23.5 +/- 3.3%; IF + bovine Lf 22.7 +/- 4.9%. Therefore, infant monkeys absorb and retain iron similarly from human milk and infant formula. Supplementation of infant formula with human or bovine Lf resulted in similar iron retention to that of ferrous sulfate-supplemented infant formula.

Animals↗
PubMed1990

Influence of dietary zinc and iron on zinc retention in pregnant rhesus monkeys and their infants.

To test the idea that zinc uptake may be enhanced in conditions of zinc deficiency, we fed rhesus monkeys diets containing either 4 micrograms zinc (low-zinc group) or 100 micrograms zinc (controls) throughout pregnancy and lactation. Each group was divided into two subgroups, one of which received an iron supplement (4 mg ferrous sulfate/kg/day). We investigated iron supplements because excess dietary iron has been suggested to inhibit zinc absorption. 65Zn retention from labeled meals was studied in the dams during pregnancy and lactation and in their 10-day-old infants. In both the mothers and the infants, zinc absorption/retention, as measured by whole-body counting, was more than 25% higher in the low-zinc group than in the controls. Iron supplementation had no effect on initial dietary zinc retention, but resulted in a reduction in whole-body 65Zn turnover. Thus, changes in zinc status and dietary factors such as iron can affect net retention and turnover of zinc in pregnant and lactating primates fed low-zinc diets.

Animals↗
PubMed1989

Abnormal zinc content in human milk. Risk for development of nutritional zinc deficiency in infants.

An abnormally low concentration of zinc in mother's milk has been associated with clinical nutritional zinc deficiency in premature and term newborns. Defective mammary gland secretion of zinc was suggested as the causative factor. We investigated whether low milk zinc concentration might be reflected in an abnormality of the distribution of zinc between casein, whey, and fat components of the milk, in a reduction in the levels of milk citrate, a zinc-binding ligand, or in abnormal levels of copper and iron. Milk from mothers of four low-birth-weight infants was identified as being deficient in zinc content for the lactational stage. One infant had clinical signs of nutritional zinc deficiency. For two of the three infants with subclinical deficiencies in whom balance study data were available, the apparent zinc balance was negative (-5.7 and -6.0 mumol/kg per day). These milks were examined for content and distribution of zinc, copper, and iron, and citrate concentration. Although total zinc concentration (4.5 to 17.2 mumol/L) was below the 95% prediction interval (15.2 to 59.7 mumol/L) for the lactational stage, the distribution of zinc was normal between milk components. Levels of citrate (1.46 to 5.13 mmol/L) were also within normal limits, as were levels of copper (0.27 to 0.85 mumol/L and iron (0.41 to 1.13 mumol/L). We concluded that there was no indirect evidence of a secretory abnormality in milk zinc deficiency, but speculated that there might instead be an abnormality of zinc uptake by the mammary gland from the plasma.

Breast Feeding↗
PubMed1989

Manganese absorption from human milk, cow's milk, and infant formulas in humans.

Manganese absorption from human milk, cow's milk, and infant formulas was studied in humans by using extrinsic labeling of the diets with manganese 54 or manganese 52 and whole-body retention measurements. The fractional manganese absorption from human milk (8.2% +/- 2.9%) was significantly different when compared with cow's milk (2.4% +/- 1.7%), soy formula (0.7% +/- 0.2%), and whey-preponderant cow's milk formula with 12 mg/L of iron (1.7% +/- 1.0%) and without iron fortification (2 mg/L of iron) (3.1% +/- 2.8%), while no significant difference was observed between a whey-preponderant cow's milk formula with 7 mg/L of iron (5.9% +/- 4.8%) and human milk. The total amount of absorbed manganese was significantly higher from the non--iron-fortified cow's milk formula (2 mg/L of iron) as compared with human milk, while no significant differences were observed for the other milks and formulas.

Absorption↗
PubMed1989

Partition of nitrogen intake and excretion in low-birth-weight infants.

Although nitrogen balance studies have been carried out in low-birth-weight infants, few have partitioned the nitrogen into its components. In this study, 72-hour balance studies were conducted in 24 low-birth-weight infants (gestational age, 30.7 +/- 1.6 weeks; birth weight 1.36 +/- 0.25 kg) fed their mothers' milk (preterm milk) or 50% preterm milk and 50% formula. Total nitrogen, nonprotein nitrogen, and whey protein intake and excretion were measured. Total nitrogen intake (preterm milk group, 452 +/- 138 mg/kg per day; preterm + formula group, 406 +/- 93 mg/kg per day), absorption (85%), and retention (71%) were not significantly different between groups. Intact and fragments of secretory IgA and lactoferrin were detected in soluble fecal extracts, and represented 25% and 9% of intake, respectively. Feeding preterm milk allows for nitrogen accretion similar to intrauterine growth rates for 5 weeks postnatally, and provides potentially functional proteins for the low-birth-weight infant.

Birth Weight↗
PubMed1989

Higher retention of manganese in suckling than in adult rats is not due to maturational differences in manganese uptake by rat small intestine.

To test the hypothesis that the high absorption of manganese (Mn) in suckling rats compared to weanling rats is due in part to maturational differences in mucosal cell uptake of Mn, uptake kinetics of Mn were examined in isolated brush-border membrane vesicles prepared from the small intestine of rats at various ages (d 14, d 18, d 21). Initial uptake of Mn was rapid by vesicles from all age groups and reached an equilibrium plateau by 5 min in vesicles from suckling rats (d 14) and 10 min in vesicles from weanling rats (d 18, d 21). Uptake of Mn was associated with an osmotically active space. Uptake velocity was similar in all age groups and was nonsaturable at Mn concentration of 1-90 microM. The data were representative of a diffusional transport process. Mn uptake did not appear to be influenced by a putative ligand, L-histidine. However, incubations that included ascorbate did result in increased uptake of Mn by membrane vesicles. The results do not support the hypothesis that age-related differences in Mn retention in rats are due to maturational differences in the transport of Mn across small-intestinal brush-border membranes.

Age Factors↗