Regulation of iron absorption in Hfe mutant mice.
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Hereditary hemochromatosis is most commonly caused by homozygosity for a point mutation (C282Y) in the human hemochromatosis gene (HFE). The mechanism by which HFE regulates iron absorption is not known, but the C282Y mutation results in loss of cell surface expression of the human hemachromatosis protein (HFE) and hyperabsorption of iron by the duodenal enterocyte. Mice homozygous for a deletion in the mouse hemochromatosis gene (Hfe) or a mutation equivalent to that seen in human hereditary hemochromatosis (C282Y) were compared with wild-type animals for their ability to regulate iron absorption. Both mutant strains hyperabsorbed (59)Fe administered by gavage. Feeding a diet supplemented with carbonyl iron resulted in a more than 5-fold reduction of (59)Fe absorption in both wild-type and mutant mouse strains. Similarly, the iron loading associated with age in Hfe mutant mice resulted in nearly a 4-fold reduction in iron absorption. When mice were stimulated to absorb iron either by depleting iron stores or by inducing erythropoiesis, wild type and Hfe mutant strains increased absorption to similar levels, approximately 5-fold over control values. Our data indicate that Hfe mutant mice retain the ability to regulate iron absorption. Mouse hemachromatosis protein (Hfe) plays a minor role in down-regulation but does not influence the up-regulation of iron absorption. (+info)
Iron status of infants fed low-iron formula: no effect of added bovine lactoferrin or nucleotides.
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BACKGROUND: The appropriate level of iron fortification in infant formula remains undetermined. OBJECTIVES: We compared hematologic indexes and iron-status indicators in infants who were either breast-fed or fed formula with concentrations of 2 or 4 mg Fe/L and evaluated the effects of providing part of the iron as bovine lactoferrin and of adding nucleotides. DESIGN: Healthy term infants were exclusively breast-fed (n = 16) or fed formula (n = 10-12) from age 4 +/- 2 wk to 6 mo. Anthropometric measures were taken monthly, and blood samples were taken at 1, 4, and 6 mo. Hematologic indexes; indicators of iron, zinc, and copper status; and erythrocyte fatty acids were assessed. RESULTS: No significant differences in hematology or iron status were observed between groups at 4 and 6 mo of age. Although 34% of all infants had a hemoglobin concentration <110 g/L at 6 mo, the absence of iron deficiency or defective erythropoiesis suggests that this hemoglobin cutoff is too high for this age group. Neither the source or the concentration of iron in formula nor fortification with nucleotides had any significant effect on serum zinc or copper, and nucleotide fortification did not affect erythrocyte fatty acids. CONCLUSIONS: A concentration of 1.6 mg Fe/L formula meets the iron requirement of healthy term infants aged +info)
Long-term effects of histidine depletion on whole-body protein metabolism in healthy adults.
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The essentiality of histidine in healthy adults is a controversial topic. To study the potential metabolic effects of a lack of exogenous histidine, four healthy adults consumed a histidine-free diet, with adequate energy and 1.0 g/(kg. d) of an L-amino acid mixture for 48 d. Protein metabolism was monitored every 4 d by using indicator amino acid (L-[1-(13)C]phenylalanine) oxidation (in four subjects) and [(15)N]glycine (in one subject). Urine samples (24-h) were collected for measurement of urea, total nitrogen, creatinine, 3-methylhistidine (3-MH), histidine and beta-alanine. Albumin, transferrin and hematologic concentrations were measured on d 0, 24 and 48. Urinary excretion of nitrogen, urea, creatinine and 3-MH were not affected by the histidine-free diet. However, there was a significant (P < 0.001) linear decline (24-28%) in whole-body protein turnover. Significant (P < 0.05) decreases in albumin (12%), transferrin (17%) and hemoglobin (Hb) (11%) concentrations occurred slowly over the histidine depletion period. The urinary excretion of beta-alanine (an index of carnosine catabolism) generally increased in the smallest subject during the consumption of histidine-free diet. This study demonstrates that a lack of histidine in the diet for a prolonged period resulted in an accommodation of protein turnover and phenylalanine oxidation, measured by the (13)C-phenylalanine indicator amino acid. The extensive metabolic accommodation, together with decreases in Hb, albumin and transferrin during histidine depletion, leaves unresolved the issue of whether histidine is a dietary essential amino acid in healthy adults. (+info)
The diagnostic criteria for iron deficiency in infants should be reevaluated.
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Diagnostic criteria for iron deficiency (ID) and iron deficiency anemia (IDA) in infants are poorly defined. Our aim was to establish appropriate cut-off values for hemoglobin (Hb), plasma ferritin, erythrocyte mean cell volume (MCV), zinc protoporphyrin (ZPP) and soluble transferrin receptors (TfR) in infancy. Exclusively breast-fed infants (n = 263) in Honduras and Sweden were randomly assigned to receive iron supplementation or placebo, and blood samples were obtained at 4, 6 and 9 mo of age. Reference ranges were determined using three different approaches for defining iron-replete infants. The usefulness of several variables for predicting the Hb response to iron was evaluated. We found the following 2 SD cut-off values in iron-replete infants: Hb <105 g/L at 4-6 mo and <100 g/L at 9 mo; ZPP >75 micro mol/mol heme at 4-6 mo and >90 micro mol/mol heme at 9 mo; ferritin <20 micro g/L at 4 mo, <9 micro g/L at 6 mo and <5 micro g/L at 9 mo; and TfR >11 mg/L at 4-9 mo. The Hb response to iron was not a useful definition of IDA at 4 mo of age. Hb, MCV and ZPP at 6 mo as well as growth variables predicted the Hb response at 6-9 mo, but ferritin and TfR at 6 mo did not. We conclude that there is need for a reevaluation of the definitions of ID and IDA in infants. (+info)
W/Wv marrow stromal cells engraft and enhance early erythropoietic progenitors in unconditioned Sl/Sld murine recipients.
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Transplantation of marrow stromal cells may provide a means of modulating hematopoiesis and serve as a form of cell therapy. We employed a murine transplant model using Sl/Sl(d) mice, which have macrocytic anemia due to defective expression of stem cell factor (SCF) on bone marrow stromal cells. Donor cells were derived from the complementary mutant strain W/W(v), which also exhibit anemia, due to mutations in c-kit, the SCF receptor expressed on hematopoietic stem cells. The strength of this model is that any correction of the Sl/Sl(d) anemia from the infusion of W/W(v) stromal cells can be attributed to the effect of the stromal cells and not to contaminating W/W(v) hematopoietic stem cells, a major concern in experiments involving wild-type animals. Cultured stromal cells were infused into unconditioned non-splenectomized Sl/Sl(d) mice. Engraftment of donor stromal cells reached levels of up to 1.0% of total marrow cells 4 months post transplant. However, stromal engraftment was not detectable in the spleen. Recipients of W/W(v) stroma showed a significant increase in the committed erythroid progenitors compared with those receiving Sl/Sl(d) stromal cells: 109 +/- 26 vs 68 +/- 5 CFU-E per 10(5) BMC, P = 0.002; 25 +/- 10 vs 15 +/- 5 BFU-E per 10(5) BMC, P = 0.037, for W/W(v) and Sl/Sl(d) stroma recipients, respectively. Despite this increase in erythroid progenitors, the anemia was not corrected. Our data suggest that in this murine model, splenic erythropoiesis may influence stromal cell therapy, and that higher levels of marrow engraftment may be necessary to obtain a clinically significant effect. (+info)
Longitudinal study of diet and iron deficiency anaemia in infants during the first two years of life.
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The objectives of this study were: (i) to investigate the energy, iron, zinc, calcium and vitamin C intakes of a group of healthy term Caucasian infants resident in Dunedin, New Zealand, prospectively from age 9 months to 2 years; and (ii) to determine the prevalence of iron deficiency anaemia among these infants. A self-selected sample of 74 Caucasian mothers and their infants born in Dunedin, New Zealand, between October 1995 and May 1996 were recruited. Dietary intake was determined using estimated diet records at 9, 12, 18 and 24 months of age. Haemoglobin concentration, mean corpuscular volume andzinc protoporphyrin concentration were determined at the same ages. The infants' zinc, calcium and vitamin C intakes appeared adequate. Their median iron intakes ranged from 4.3 mg (at 12 months) to 7.0 mg (at 9 months) per day and were below estimated requirements at all ages. At 9, 12 and 18 months of age, 7% (n = 4) of the infants had iron deficiency anaemia. None of the infants had iron deficiency anaemia at 24 months. The iron intakes of this group of Caucasian infants and young children appeared inadequate. However, their rate of iron deficiency anaemia was lower than has been reported in previous New Zealand studies. (+info)
Iron supplementation improves progressive fatigue resistance during dynamic knee extensor exercise in iron-depleted, nonanemic women.
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BACKGROUND: Tissue iron depletion may negatively affect endurance performance and muscle fatigability. OBJECTIVE: We investigated tissue-level iron depletion and progressive fatigue of the quadriceps during dynamic knee-extension exercise in young women. DESIGN: Twenty iron-depleted (serum ferritin < 20 micro g/L), nonanemic (hemoglobin > 110 g/L) women (macro x +/- SEM age: 29.1 +/- 1.2 y) received iron (iron group) or placebo (placebo group) for 6 wk in a randomized, double-blind trial (n = 10 per group). A protocol integrating 2-3-s maximal voluntary static contractions (MVCs) with dynamic knee extensions was used to assess fatigue. RESULTS: No significant differences between the groups in baseline iron status, MVC at rest, or MVC at the end of the protocol were observed. After treatment, serum iron and transferrin saturation increased significantly in the iron group (P = 0.02 and P = 0.03, respectively). Serum transferrin receptor concentrations increased significantly in the placebo group (P < 0.01) but not in the iron group. After treatment, the rate of decrease in MVC was attenuated in the iron group but not in the placebo group (P = 0.01). In the iron group, MVC at the sixth minute of the fatigue protocol and MVC at the end of the protocol were approximately 15% (P = 0.04) and approximately 27% higher (P < 0.01), respectively, after treatment. These improvements were not related to changes in iron-status indexes or tissue iron stores, although power was low (< 0.50) to detect these relations. CONCLUSIONS: Iron supplementation was associated with a significant improvement in muscle fatigability. Interpretation regarding the direct role of tissue iron status is limited by the study's low power to detect relations between tissue iron improvement and decreased muscle fatigue. (+info)
Reticulocyte analysis in systemic lupus erythematosus and chronic renal failure using flow cytometry.
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The number and maturation of circulating reticulocytes were measured in patients with systemic lupus erythematosus (SLE) and chronic renal failure (CRF) using an automated hematological analyzer (Technicon H*3 RTX) for their erythropoietic activities. Both SLE and CRF patients had increased reticulocyte numbers with a low degree of maturation. The SLE patients had no changes in mean reticulocyte corpuscular volume (MCVr) as compared to normal subjects (110.20 +/- 15.43 fl. in SLE and 110.39 +/- 5.09 fl. in normal), whereas CRF patients had significantly increased mean corpuscular reticulocyte volume (MCVr = 120.99 +/- 8.09 fl., p-value = 0.0019 as compared with normal). Three cases of SLE with nephrotic syndrome (NS) had high degree of MCVr (113.4, 125.0 and 133.1 fl., respectively). The renal involvement in SLE patients and CRF patients may associate with increased reticulocyte corpuscular volume. (+info)