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Biomedical subjects

B Lönnerdal

Publications and source records attributed to B Lönnerdal.

At least 37 records · Page 2Linked to original sources

Long-term marginal intakes of zinc and retinol affect retinol homeostasis without compromising circulating levels during lactation in rats.

Marginal zinc or vitamin A intake is more common than previously thought in industrialized and developing countries, with pregnant and lactating women believed to be particularly at risk. However, the lack of sensitive indicators of zinc and vitamin A status precludes accurate assessment of marginal nutriture. Concurrent deficiencies in zinc and vitamin A intake often coexist, and the interaction between zinc deficiency and vitamin A metabolism may confound results from epidemiologic or intervention studies. To investigate effects of a maternal diet chronically restricted in zinc or vitamin A intake on indices of vitamin A metabolism, we fed rats a control diet (C) or a diet marginal in zinc (ZD), marginal in vitamin A (AD), marginal in both (DD) or pair-fed to DD (PF), preconception through lactation. Plasma retinol (ROH) was greater and retinol binding protein (RBP) was lower in rats fed ZD, AD and DD compared with those fed C. Hepatic cellular retinol binding protein (CRBP) expression was greater than controls in rats fed ZD and AD and lower in those fed DD, whereas RBP expression was greater in the DD- and PF-fed groups compared with rats C. Mammary gland CRBP and RBP expression were not affected by the diets. Milk ROH was lower in rats fed AD, and milk RBP was lower in those fed ZD and DD compared with rats fed C. In summary, chronic, marginal intake of zinc or vitamin A resulted in alterations in tissue retinol metabolism and milk retinol levels without decreasing plasma zinc, retinol or ROH:RBP during lactation. These observations are of concern because these parameters, which are commonly used to assess zinc and vitamin A status, may lead to misassessment of marginal zinc or vitamin A nutriture in some human populations.

Animals↗

Changes in protein and nutrient composition of milk throughout lactation in dogs.

OBJECTIVE: To evaluate changes in protein and nutrient composition of milk throughout lactation in dogs. SAMPLE POPULATION: Milk samples collected from 10 lactating Beagles. PROCEDURE: Milk samples were collected on days 1, 3, 7, 14, 21, 28, 35, and 42 after parturition and analyzed to determine concentrations of nitrogen, nonprotein nitrogen, casein, whey proteins, amino acids, lipids, lactose, citrate, minerals, and trace elements. Optimum conditions for separating casein from whey proteins and distribution of milk proteins throughout lactation were assessed by use of polyacrylamide gel electrophoresis. RESULTS: Protein concentration was high in samples collected on day 1 (143 g/L), decreased through day 21 (68.4 g/L), and increased thereafter. Concentration of nonprotein nitrogen did not change throughout lactation (5.7 to 9.9% of total nitrogen content). Casein-to-whey ratio was approximately 70:30 and remained constant throughout lactation. Lactose concentration increased from 16.6 g/L on day 1 to 34.0 to 40.2 g/L on days 7 to 42. Lipid concentration ranged from 112.5 to 1372 g/L. Citrate concentration increased from day 1 (4.8 mM) to day 7 (6.6 mM), then gradually decreased until day 42 (3.9 mM). Iron, zinc, copper, and magnesium concentrations decreased during lactation, whereas calcium and phosphorus concentrations increased. Calcium-to-phosphorus ratio remained constant throughout lactation (approx 1.6:1). Energy content of milk ranged from 1,444 to 1,831 kcal/L. CONCLUSIONS AND CLINICAL RELEVANCE: Protein and nutrient composition of milk changes throughout lactation in dogs. These data can provide valuable information for use in establishing nutrient requirements of puppies during the suckling period.

Amino Acids↗

PCR cloning and baculovirus expression of human lactoperoxidase and myeloperoxidase.

Lactoperoxidase (LPO) and myeloperoxidase (MPO) have been identified previously in human milk. These peroxidases have antimicrobial activity and presumably contribute to the protective functions of milk. In this study, we amplified genes encoding LPO and MPO from human mammary gland cDNA by the polymerase chain reaction (PCR). These genes were expressed in a baculovirus-insect cell system. Peroxidase activity was observed in the culture supernatant of Tricoplusia ni cells infected with the recombinant viruses and the levels increased upon addition of delta-aminolevulinic acid. Purified recombinant human LPO and MPO, both with a molecular mass of about 80 kDa, showed properties similar to bovine LPO and human MPO, respectively, in terms of absorption spectrum, sensitivity to dapsone, specificity for chloride ions, and reactivity with anti-bovine LPO or anti-MPO antibodies. Our data suggest that this expression system is useful for studying the catalytic mechanism and biological significance of these human peroxidases.

Baculoviridae↗

Bioavailability of zinc and its binding to casein in milks and formulas.

Differences in zinc bioavailability among milk and formulas may be attributed to binding of zinc to various ligands. We determined the distribution of zinc and protein at different pHs and zinc and calcium concentrations. We used radiolabelled cow's milk, human milk, whey-predominant (WPF) and casein-predominant (CPF) infant formula. Lowering the pH changed zinc and protein distribution: zinc shifted from pellet (casein) to whey in cow's milk, from fat to whey in human milk and from fat and pellet to whey in formulas. Protein shifted from whey to pellet in human milk and from whey and pellet to fat in formulas. Increasing zinc and calcium concentrations shifted protein and zinc from pellet to whey for cow's milk and from whey and pellet to fat for the formulas. Protein distribution was not affected by calcium or zinc addition in human milk or CPF, while zinc shifted from whey to fat in human milk and from fat and pellet to whey in CPF. Zinc and calcium binding to isolated bovine or human casein increased with pH. At 500 mg/L of zinc, bovine casein bound 32.0 +/- 1.8 and human casein 10.0 +/- 0.9 mg zinc/g protein. At 500 mg/L of calcium, calcium was preferentially bound over zinc. Adding calcium and zinc resulted in 32.0 +/- 1.8 mg zinc/g bound to bovine casein and 17.0 +/- 0.8 mg zinc/g to human casein, while calcium binding was low. Suckling rat pups dosed with 65Zn labelled infant diets were killed and individual tissues were gamma counted. Lower zinc bioavailability was found for bovine milk at pH = 4.0 (%65Zn in liver = 18.7+1.4) when compared to WPF (22.8 +/- 1.6) or human milk (26.9 +/- 0.8). Lowering the pH further decreased zinc bioavailability from human milk, but not from cow's milk or WPF. Knowledge of the compounds binding minerals and trace elements in infant formulas is essential for optimizing zinc bioavailability.

Animals↗

Identification of lactoperoxidase in mature human milk.

Myeloperoxidase (MPO) derived from milk leukocytes and lactoperoxidase (LPO) secreted from the mammary gland have been identified previously in human colostrum. These peroxidases are known to play host defensive roles through antimicrobial activity. The goals of this study were to measure the peroxidase activity in mature human milk and to characterize the enzyme responsible for the activity. As determined using 3,3',5,5'-tetramethylbenzidine as substrate, whey prepared from human milk samples obtained 1 and 5 months postpartum showed levels of peroxidase activity equivalent to 0.13 +/- 0.18 and 0.24 +/- 0.21 microg/mL bovine LPO (bLPO; n = 13), respectively. Whey from early milk was fractionated into two peaks of peroxidase activity by cation-exchange chromatography; the peroxidase in the first peak was sensitive to dapsone, which is an inhibitor of LPO, whereas the second peroxidase was not. Whey from mature milk showed only the first peak. Purified bLPO and MPO showed chromatographic behaviors that were similar to the first and second peaks, respectively. The dapsone-sensitive peroxidase from mature milk was further purified (952-fold from whey) by hydrophobic interaction chromatography. This preparation showed two bands with molecular masses of 80 and 90 kDa by polyacrylamide gel electrophoresis and immunoblotting using an antibody against bLPO. After deglycosylation, two distinct proteins with lower molecular weights were observed. Amino acid sequencing indicated that both of these proteins are LPO. These results provide evidence that LPO is present in mature human milk and that it is responsible for most of the peroxidase activity in mature milk.

Journal Article↗

A folding variant of alpha-lactalbumin with bactericidal activity against Streptococcus pneumoniae.

This study describes an alpha-lactalbumin folding variant from human milk with bactericidal activity against antibiotic-resistant and -susceptible strains of Streptococcus pneumoniae. The active complex precipitated with the casein fraction at pH 4.6 and was purified from casein by a combination of anion exchange and gel chromatography. Unlike other casein components, the active complex was retained on the ion-exchange matrix and eluted only with high salt. The eluted fraction showed N-terminal and mass spectrometric identity with human milk alpha-lactalbumin, but native alpha-lactalbumin had no bactericidal effect. Spectroscopic analysis demonstrated that the active form of the molecule was in a different folding state, with secondary structure identical to alpha-lactalbumin from human milk whey, but fluctuating tertiary structure. Native alpha-lactalbumin could be converted to the active bactericidal form by ion-exchange chromatography in the presence of a cofactor from human milk casein, characterized as a C18:1 fatty acid. Analysis of the antibacterial spectrum showed selectivity for streptococci; Gram-negative and other Gram-positive bacteria were resistant. The folding variant of alpha-lactalbumin is a new example of naturally occurring molecules with antimicrobial activity.

Anti-Bacterial Agents↗

A follow-up study of serum ferritin and transferrin receptor concentrations in Swedish adolescents at age 17 age 15.

UNLABELLED: Serum ferritin and serum transferrin receptor concentrations, growth and food habits were studied in healthy Swedish boys (n = 103) and girls (n = 124) at the age of 17 y and compared with those in the same adolescents at age 15. Between these ages, serum transferrin receptor increased significantly in both boys and girls. Serum ferritin increased significantly in boys but not in girls. The transferrin receptor/ferritin ratio increased significantly in girls but not in boys, indicating insufficient iron stores in the 17-y-old girls in relation to erythropoiesis and iron needs. Between 15 and 17 y the boys' frequency of consumption of milk and bread decreased, while they more often consumed pasta, cheese and coffee. The girls decreased their frequency intake of fat products, milk and meat. The frequency of meat consumption emerged as the single significant predictor for serum ferritin <12 microg/L in girls, but not in boys. The median daily iron intake, determined in a subsample, decreased in boys from 18.7 to 13.6 mg and in girls from 14.1 to 8.8 mg, and the decrease was to a large extent due to cessation of iron fortification of flour. CONCLUSIONS: The results indicate insufficient iron stores in the 17-y-old girls in relation to erythropoiesis and iron needs, but more favourable iron stores in the boys. The absence of a significant decrease in mean serum ferritin despite rapid growth suggests that the earlier iron fortification of flour only marginally contributed to the iron status of Swedish adolescents of this age group.

Adolescent↗

Serum leptin concentrations in infants: effects of diet, sex, and adiposity.

BACKGROUND: Leptin, the product of the obese (ob) gene, is a regulator of food intake and energy metabolism. Immunoreactive leptin was detected recently in breast milk and it has been hypothesized that leptin may be absorbed and may contribute to differences in body composition between breast-fed and formula-fed infants. OBJECTIVE: The objective was to evaluate whether diet, adiposity, or sex affect plasma leptin in breast-fed and formula-fed infants. DESIGN: Venous blood samples were drawn from healthy, exclusively breast-fed or formula-fed Swedish infants at 1, 4, and 6 mo of age (n = 193) and from 12-mo-old Finnish infants (n = 79). Anthropometric measurements were made and plasma samples were analyzed for leptin, insulin, and glucose. RESULTS: There were no significant differences in plasma leptin between formula-fed and breast-fed infants at 1 and 4 mo of age, whereas formula-fed infants had significantly higher ( approximately 5%) leptin concentrations at 6 mo of age. Similar results were observed after correction for BMI. Plasma leptin was 15-25% higher in female than in male infants at 1, 4, and 12 mo of age (P < 0.05), also after correction for BMI. When all infants were analyzed together, a positive correlation (r = 0.34, P < 0.0001) was found between plasma leptin and BMI. Very low leptin concentrations were found in breast milk after centrifugation and the high concentrations reported previously were likely due to interference in the assay by milk fat. CONCLUSIONS: Plasma leptin concentrations are not higher in breast-fed than in formula-fed infants; however, sex and adiposity affect leptin concentrations even at this early age.

Blood Glucose↗

Functional and molecular responses of human intestinal Caco-2 cells to iron treatment.

BACKGROUND: Divalent metal transporter 1 (DMT1), HFE, and stimulator of iron transport (SFT) are transmembrane proteins that have been implicated in the regulation of iron homeostasis. OBJECTIVE: The objective of this study was to investigate whether absorption and transepithelial movement of iron correlated with gene expression of DMT1, HFE, and SFT in an experimental model of human absorptive enterocytes. DESIGN: Caco-2 cells were exposed to iron-supplemented media in either the presence or the absence of serum for 24, 72, and 168 h. At each time point, the uptake and transepithelial movement of iron were examined and gene expression of DMT1, HFE, and SFT was measured. Manganese and zinc absorption was also examined at 168 h. RESULTS: Iron treatment in the presence or absence of serum reduced the uptake and transepithelial movement of iron by approximately 50% after 72 and 168 h. No effect was observed at 24 h. The uptake and transepithelial movement of manganese were similar to those of iron at 168 h, whereas the effects on zinc were less pronounced. In the absence of serum, iron treatment was associated with a reduction of DMT1 expression by 50% at 72 and 168 h. HFE expression was dependent on serum, but iron treatment did not alter HFE expression. SFT expression was not affected by iron. CONCLUSIONS: Iron treatment decreased cellular uptake of iron, manganese, and zinc, suggesting that these metals may utilize the same apical transporter. The transepithelial movement of iron and manganese, but not of zinc, was reduced across iron-treated Caco-2 cells, suggesting that iron and manganese are regulated by the same mechanism at the basolateral membrane. The gene expression of DMT1, HFE, and SFT did not fully correlate with the functional responses of Caco-2 cells. This may have been a result of posttranscriptional regulation of these genes or regulation of other genes involved in the uptake and transepithelial movement of iron in Caco-2 cells.

Absorption↗

Dietary factors influencing zinc absorption.

Marginal zinc deficiency and suboptimal zinc status have been recognized in many groups of the population in both less developed and industrialized countries. Although the cause in some cases may be inadequate dietary intake of zinc, inhibitors of zinc absorption are most likely the most common causative factor. Phytate, which is present in staple foods like cereals, corn and rice, has a strong negative effect on zinc absorption from composite meals. Inositol hexaphosphates and pentaphosphates are the phytate forms that exert these negative effects, whereas the lower phosphates have no or little effect on zinc absorption. The removal or reduction of phytate by enzyme (phytase) treatment, precipitation methods, germination, fermentation or plant breeding/genetic engineering markedly improves zinc absorption. Iron can have a negative effect on zinc absorption, if given together in a supplement, whereas no effect is observed when the same amounts are present in a meal as fortificants. Cadmium, which is increasing in the environment, also inhibits zinc absorption. The amount of protein in a meal has a positive effect on zinc absorption, but individual proteins may act differently; e.g., casein has a modest inhibitory effect of zinc absorption compared with other protein sources. Amino acids, such as histidine and methionine, and other low-molecular-weight ions, such as EDTA and organic acids (e.g., citrate), are known to have a positive effect on zinc absorption and have been used for zinc supplements. Knowledge about dietary factors that inhibit zinc absorption and about ways to overcome or remove these factors is essential when designing strategies to improve the zinc nutrition of vulnerable groups.

Adult↗

Regulation of mineral and trace elements in human milk: exogenous and endogenous factors.

Breast-fed infants are dependent on an adequate supply of minerals and trace elements for normal growth and development. For most of these elements, the mammary gland appears to have developed mechanisms to regulate their concentrations, even when the maternal diet varies considerably or maternal conditions are affected by different challenges. For some elements, however, there appears to be little or no such regulation. Increased knowledge about these mechanisms, or their absence, and to what extent they may compensate for adverse maternal conditions, including poor nutrition, will help identify infants and women at risk for deficiencies of these nutrients.

Biological Availability↗

Protein binding of mercury in milk and plasma from mice and man--a comparison between methylmercury and inorganic mercury.

Inorganic mercury has previously been shown to be excreted to milk from plasma to a higher extent than methylmercury. Protein binding of mercury as methylmercury and inorganic mercury in whey and plasma from mouse and man was studied in order to get a better understanding of the transport of mercury into milk. Mice were administered a single i.v. dose of 0.25 mg Hg/kg body weight labelled with (CH3)203HgCl or 203HgCl2, resulting in 11 ng Hg/g milk and 38 ng Hg/g milk after 1 h, respectively. Milk and plasma from mice and man were also incubated with the respective radiolabelled compound (150 ng Hg/g milk or plasma). Casein, fat and whey fractions in milk from methylmercury treated mice were found to contain 11, 39 and 34%, respectively, and from inorganic mercury treated mice 31, 15 and 41%, respectively, of the total amount of mercury in milk. Serum albumin was a major mercury binding protein in whey and plasma from mice for both methylmercury and inorganic mercury, as demonstrated by FPLC gel filtration and anion-exchange chromatography and further characterised by SDS-PAGE for whey. In addition, anion-exchange chromatography indicated that inorganic mercury, but not methylmercury, in whey from mouse milk formed a dimer of serum albumin. The unbound fraction of mercury in whey and plasma from mice was very small (<0.7%), and somewhat higher in plasma and whey from man. It is concluded, that the unbound fraction in plasma cannot be a determining factor for the observed differences in milk excretion between the two mercury compounds. Instead, it is suggested that methylmercury and to some extent inorganic mercury are transferred from plasma into milk using albumin as a passive carrier.

Adult↗

Randomized, community-based trial of the effect of zinc supplementation, with and without other micronutrients, on the duration of persistent childhood diarrhea in Lima, Peru.

OBJECTIVE: To determine whether supplemental zinc, with or without additional micronutrients, affects the severity and duration of persistent childhood diarrhea and the rate of nutritional recovery. DESIGN: The study was a community-based, double-blind, randomized trial implemented in a shanty town in Lima, Peru. Children aged 6 to 36 months with persistent (>/=14 days) diarrhea received daily, for 2 weeks, a placebo (group P, n = 136) or a supplement of 20 mg of zinc, either with (group Z+VM, n = 137) or without (group Z, n = 139) additional vitamins and minerals. Symptoms of illness were recorded daily, and biochemical and anthropometric assessments were completed at baseline and on day 15. RESULTS: The treatment groups were similar at baseline with regard to the characteristics of the presenting episode, anthropometric data, and plasma zinc concentration. The children consumed, on average, 95% (group P), 94% (group Z), or 88% (group Z+VM) of the supplement (P <.001). The plasma zinc concentration did not change significantly from baseline to day 15 in group P (4 microg/dL) but increased by 38 microg/dL in group Z and 14 microg/dL in group Z+VM. The median duration of diarrhea after starting treatment was 1 day; among children who continued to have diarrhea, there was a significant effect of treatment on diarrheal duration (P =.04, analysis of covariance). Specifically, the duration of illness was significantly reduced by 28% in children in group Z (P =.01) and by 33% in girls in group Z+VM (P =.04). There were no differences in the severity of the episode by treatment group. CONCLUSION: There was a significant reduction in the duration of persistent diarrhea in selected subgroups of zinc-supplemented ambulatory patients in this population.

Analysis of Variance↗

Novel angiotensin-I-converting enzyme inhibitory peptides derived from recombinant human alpha s1-casein expressed in Escherichia coli.

Recombinant human alpha s1-casein expressed in Escherichia coli was purified and digested with trypsin in an attempt to find peptides with angiotensin-I-converting enzyme (ACE) inhibitory activity. Three novel ACE inhibitory peptides, A-II, B-II and C, were isolated and their amino acid sequences identified as Tyr-Pro-Glu-Arg (residues 8-11), Tyr-Tyr-Pro-Gln-Ile-Met-Gln-Tyr (residues 136-143) and Asn-Asn-Val-Met-Leu-Gln-Trp (residues 164-170) respectively. ACE inhibitory activities were measured for the corresponding synthetic peptides, and the ACE IC50 (the amount of peptide causing 50% inhibition of ACE activity) values of A-II, B-II and C estimated to be 132.5, 24.8 and 41.0 mumol/l respectively. Peptides A-II and C were resistant to further digestion by pepsin, whereas peptide B-II was hydrolysed. All three peptides were resistant to digestion by chymotrypsin. These ACE inhibitory peptides may prove useful for oral administration in the treatment of hypertension.

Amino Acid Sequence↗

Inositol phosphates influence iron uptake in Caco-2 cells.

Phytate, inositol hexaphosphate (InsP(6)), may be hydrolyzed to inositol phosphates with lower degree of phosphorylation, i.e., inositol penta- to monophosphates (InsP(5)-InsP(1)), during food processing. Each of these lower inositol phosphates exists in different isomeric forms. The objective of this study was to determine if different isomers of InsP(3)-InsP(5) (Ins(1,2,4)P(3), Ins(1,2,3)P(3), Ins(1,2,6)P(3), Ins(1,3,4)P(3), Ins(1,2,3,4)P(4), Ins(1,2,5,6)P(4), Ins(1,2,4,5,6)P(5), and Ins(1,3,4,5,6)P(5)) and InsP(6) affect the uptake of iron. We studied the iron absorption in vitro using the human intestinal epithelial cell line, Caco-2. Addition of a 2-fold molar excess of InsP(6) or InsP(5) in proportion to Fe (1 h incubation at 37 degrees C) reduced iron uptake by 46-52% (p < 0.001). Neither InsP(4) isomers nor InsP(3) isomers affected iron uptake significantly at 1 h incubation with a molar InsP:Fe level of 2:1. Iron uptake was shown to not be a function of the isomeric form of inositol phosphates. The inositol phosphate isomers did not seem likely to interact with each other through iron to form more stable iron complexes. At a molar InsP:Fe level of 20:1 an inhibitory effect of InsP(4) was found, while InsP(3) did not affect the iron absorption even at a 20-fold molar excess.

Biological Transport↗

Effect of reducing the phytate content and of partially hydrolyzing the protein in soy formula on zinc and copper absorption and status in infant rhesus monkeys and rat pups.

BACKGROUND: Although soy formulas have been designed to meet the nutrient requirements of human infants, they also contain phytate, which may negatively affect trace element absorption. OBJECTIVE: We evaluated the effect of removing phytate on zinc and copper absorption and status in infant rhesus monkeys and suckling rat pups and evaluated differences between intact and partially hydrolyzed soy protein. DESIGN: In monkeys, regular and low-phytate soy formulas were fed exclusively for 4 mo and whole-body absorption and retention of 65Zn, 67Cu, 59Fe, 54Mn, and 47Ca were determined at different time points with a whole-body counter. Subsequently, zinc and copper absorption from several human infant formulas and the effect of phytate concentration were evaluated in suckling rat pups by using 65Zn and 64Cu. Finally, infant rhesus monkeys were fed low-phytate formulas with intact or hydrolyzed soy protein for 4 mo and plasma zinc and copper were measured monthly. RESULTS: In the first monkey study, zinc absorption at 1 mo was higher from low-phytate soy formula (36%) than from regular soy formula (22%), whereas there was no significant difference between groups in the absorption of other minerals. Plasma copper was significantly lower in monkeys fed low-phytate soy formula from 2 to 4 mo. In rat pups, zinc absorption was significantly higher from low-phytate soy formula (78%) than from regular soy formula (51%) and hydrolysis of the protein had no significant effect. Phytate content or protein hydrolysis did not significantly affect copper absorption. In the second monkey study, plasma copper concentrations were highest in monkeys fed the low-phytate, hydrolyzed-protein soy formula. CONCLUSION: Reducing the phytate content and partially hydrolyzing the protein in soy formula had a beneficial effect on zinc and copper absorption and status in infant rhesus monkeys.

Animals↗

Randomized trial of the short-term effects of dieting compared with dieting plus aerobic exercise on lactation performance.

BACKGROUND: Limiting postpartum weight retention is important for preventing adult obesity, but the effect of weight loss on lactation has not been studied adequately. OBJECTIVE: We evaluated whether weight loss by dieting, with or without aerobic exercise, adversely affects lactation performance. DESIGN: At 12+/-4 wk postpartum, exclusively breast-feeding women were randomly assigned for 11 d to a diet group (35% energy deficit; n = 22), a diet plus exercise group (35% net energy deficit; n = 22), or a control group (n = 23). Milk volume, composition, and energy output; maternal weight, body composition, and plasma prolactin concentration; and infant weight were measured before and after the intervention. RESULTS: Weight loss averaged 1.9, 1.6, and 0.2 kg in the diet, diet + exercise, and control groups, respectively (P < 0.0001) and was composed of 67% fat in the diet group and nearly 100% fat in the diet + exercise group. Change in milk volume, composition, and energy output and infant weight did not differ significantly among groups. However, there was a significant interaction between group and baseline percentage body fat: in the diet group only, milk energy output increased in fatter women and decreased in leaner women. The plasma prolactin concentration was higher in the diet and diet + exercise groups than in the control group. CONCLUSIONS: Short-term weight loss (approximately 1 kg/wk) through a combination of dieting and aerobic exercise appears safe for breast-feeding mothers and is preferable to weight loss achieved primarily by dieting because the latter reduces maternal lean body mass. Longer-term studies are needed to confirm these findings.

Adult↗

Identification of an alpha2-macroglobulin receptor in human mammary epithelial cells.

Several cases of zinc (Zn) deficiency in human infants caused by abnormally low concentrations of Zn in breast milk were recently reported, the underlying mechanism of which is not known. Alpha2-macroglobulin (alpha2-M), a major Zn-binding ligand in serum, presents a potential vehicle for mammary Zn uptake. This study was conducted to determine if an alpha2-M receptor is present in human mammary epithelial cells, where it may be involved in the endocytosis of alpha2-M into the mammary gland. Normal human mammary epithelial cells were grown to confluency in serum-free medium. For all binding and uptake studies, alpha2-M, preactivated with methylamine and labeled with 125I, was added to cells for varied lengths of time to determine saturation over time and at varied concentrations to determine saturation over increasing concentration of ligand. Nonspecific and competitive binding were measured by addition of a 100-fold molar excess of unlabeled alpha2-M and serum albumin or lactoferrin, respectively. Binding at 4 degreesC was specific for alpha2-M and approached saturation kinetics at 56 nmol/L. Scatchard plot analysis of the binding data demonstrated more than one binding site: a high affinity, saturable binding site and a low affinity, nonsaturable binding site. Uptake of alpha2-M at 37 degreesC was rapid and continuous over increasing concentrations of alpha2-M, and internalized alpha2-M was rapidly degraded. Results from this study present evidence for receptor-mediated uptake of alpha2-M in human mammary epithelial cells, which in turn, provides a potential mechanism for Zn acquisition by the cell.

Breast↗