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PubMed2000

Efficacy and acceptability of two iron supplementation schedules in adolescent school girls in Lima, Peru.

To assess the efficacy and acceptability of a daily and intermittent iron supplementation, a double-blind, placebo-controlled trial was conducted in a public school located in periurban Lima, Peru. Adolescent girls (n = 312), 12-18 y old, were randomly assigned to one of the following three groups: 1) 60 mg iron as ferrous sulfate daily from Monday to Friday; 2) 60 mg iron as ferrous sulfate 2 d/wk and 3 d placebo (intermittent); 3) placebo, from Monday to Friday. Field workers gave the girls supplements during school hours for 17 wk; 296 girls completed the trial. Girls took 94% of the expected dose of 85 pills. Few side effects were reported. Postintervention, hemoglobin (Hb), serum ferritin (SF) and free erythrocyte protoporphyrin (FEP) were improved significantly in the iron-supplemented groups compared with placebo (P<0.05). Daily supplements led to higher Hb increases than intermittent supplements (P<0.05), but SF and FEP were similar between the two groups. Thus, both iron supplementation schedules were efficacious in preventing iron deficiency in adolescent girls through the school system, and the daily schedule was better than the intermittent schedule at increasing Hb values and reducing anemia.

Adolescent↗

PubMed2005

Are we giving too much iron? Low-dose iron therapy is effective in octogenarians.

PURPOSE: Elderly patients are vulnerable to the dose-dependent adverse effects of iron replacement therapy. Our study examines whether low-dose iron therapy can efficiently resolve iron-deficiency anemia in patients over the age of 80 years and reduce adverse effects. SUBJECTS AND METHODS: Ninety hospitalized patients with iron-deficiency anemia were randomized to receive elemental iron in daily doses of 15 mg or 50 mg as liquid ferrous gluconate or 150 mg of ferrous calcium citrate tablets for 60 days. Thirty control patients without anemia were given 15 mg of iron for 60 days. A 2-hour iron absorption test was performed after the initial dose. Hemoglobin and ferritin levels were measured on day 1, 30, and 60 after initiating therapy. Each patient completed a weekly questionnaire regarding drug-induced adverse effects. RESULTS: Serum iron rose significantly in the anemic patients beginning 15 minutes after the first dose but not in nonanemic patients. Two months of iron treatment significantly increased hemoglobin and ferritin concentrations similarly in all 3 groups of iron-deficiency anemia patients (for example, hemoglobin levels rose from 10.0 g/dL to 11.3 g/dL with 15 mg/d of iron therapy and from 10.2 g/dL to 11.6 g/dL with 150 mg/d). Abdominal discomfort, nausea, vomiting, changes in bowel movements, and black stools were significantly more common at higher iron doses. CONCLUSIONS: Low-dose iron treatment is effective in elderly patients with iron-deficiency anemia. It can replace the commonly used higher doses and can significantly reduce adverse effects.

Aged↗

PubMed1983

Bioavailability of different sources of ferrous sulfate iron fed to anemic rats.

The bioavailability of iron from ferrous sulfate sources that had been stored for unknown periods was evaluated by using iron-deficient rats in experiment 1. The efficiency of converting dietary iron from these sources into hemoglobin varied from 60 to 84%. This variability was not explained on the basis of percent of iron in the ferrous state nor on the percent of iron in the source. The one fresh source used was reevaluated 3 months later, and its bioavailability had been reduced from 84 to 65%. The bioavailability of six fresh ferrous sulfate samples varied from 50 to 59% in experiment 2. It was concluded that, whenever ferrous sulfate is to be used as a reference source, fresh salt should be obtained to reduce variability among experiments.

Anemia, Hypochromic↗

PubMed2003

Effect of twice weekly versus daily iron treatment in Turkish children with iron deficiency anemia.

This study was designed to propose a more practical, effective, safer, inexpensive, and manageable alternative treatment of iron deficiency anemia (IDA) for the developing countries. The study involves 94 children between the ages of 5 months and 6 years who had been seen in the authors' hospital and diagnosed as having iron deficiency anemia. Ninety-four children with IDA were randomly divided into two groups: 48 children comprised the first group, which was administered conventional treatment, and 46 children comprised the second group, which was administered intermittent treatment involving iron administration 2 days a week. Twenty-three children whose age and gender distribution were compatible with the other groups were included in the study as the control group. Both groups were reevaluated for their initial hematologic parameters at the end of the treatment. When the parameters of both groups were compared with the parameters of the control group after the treatment, there were no differences between hemoglobin, hematocrit, red blood cell, mean corpuscular volume, mean corpuscular hemoglobin concentration, serum iron, and ferritin levels of conventional and intermittent treatment groups. With respect to certain parameters, such as red cell distribution, serum iron binding capacity, transferrin saturation, transferrin receptor, and transferrin receptor/log ferritin, however, intermittent treatment was superior to the conventional treatment method (p <.05). In IDA, when a conventional treatment method or an intermittent treatment method is used, there are no differences between the hematological parameters. In fact, the intermittent treatment method has been found to be superior in many parameters.

Administration, Oral↗

PubMed1996

Normalization of diabetes in spontaneously diabetic cynomologus monkeys by xenografts of microencapsulated porcine islets without immunosuppression.

Porcine pancreatic islets were microencapsulated in alginate-polylysine-alginate capsules and transplanted intraperitoneally into nine spontaneously diabetic monkeys. After one, two, or three transplants of 3-7 x 10(4) islets per recipient, seven of the monkeys became insulin independent for periods ranging from 120 to 804 d with fasting blood glucose levels in the normoglycemic range. Glucose clearance rates in the transplant recipients were significantly higher than before the graft administration and the insulin secretion during glucose tolerance tests was significantly higher compared with pretransplant tests. Porcine C-peptide was detected in all transplant recipients throughout their period of normoglycemia while none was found before the graft administration. Hemoglobin A1C levels dropped significantly within 2 mo after transplantation. While ketones were detected in the urine of all recipients before the graft administration, all experimental animals became ketone free 2 wk after transplantation. Capsules recovered from two recipients 3 mo after the restoration of normoglycemia were found physically intact with enclosed islets clearly visible. The capsules were free of cellular overgrowth. Examination of internal organs of two of the animals involved in our transplantation studies for the duration of 2 yr revealed no untoward effect of the extended presence of the microcapsules.

Animals↗

PubMed1994

Side effects of iron supplements in blood donors: superior tolerance of heme iron.

Regular blood donors were enrolled in a double-blind, parallel group study to evaluate the side effects of two iron supplements, one containing both heme iron and non-heme iron (Hemofer, 2 tablets = 18 mg iron/day), the other non-heme iron only (Erco-Fer; 1 tablet = 60 mg iron/day). No differences were found between the two alternatives in regaining predonation iron status as measured by serum ferritin and hemoglobin levels. Despite this therapeutic equivalence, participants' symptom diaries showed substantial differences in the side effects for the two treatments. The frequency of constipation (p < 0.05) and the total incidence of all side effects (p < 0.01) were significantly higher for non-heme iron when compared with the heme iron-non-heme iron combination and a placebo. The study demonstrates that a low-dose iron supplement containing both heme iron and non-heme iron (Hemofer) has fewer side effects when compared with an equipotent, traditional non-heme iron supplement.

Adult↗

PubMed2004

Once-weekly and 5-days a week iron supplementation differentially affect cognitive function but not school performance in Thai children.

Many studies have reported comparable hemoglobin response in subjects given intermittent and daily iron supplements. However, the effect of intermittent iron supplementation on impaired cognitive function, one of the serious consequences of iron deficiency among children, has not been studied. We investigated the effects of 1 d/wk (weekly) and 5 d/wk (daily) iron supplementation on changes in results of intelligence quotient (IQ), Thai language, and mathematics tests among Thai primary schoolchildren. A double-blind, randomized, placebo-controlled trial was conducted. Primary schoolchildren (n = 397) were randomly assigned to receive iron supplements daily or weekly or placebo. Ferrous sulfate (300 mg) or placebo tablets were given under direct observation by the researcher for 16 wk. Changes in IQ, and Thai language and mathematics scores were then compared. The increases in hemoglobin concentration were comparable in the weekly and daily iron supplementation groups but serum ferritin increased more in the children supplemented daily. Children receiving daily iron supplements, however, had a significantly lower increase in IQ (3 +/- 12 points) than those receiving the supplement weekly (6 +/- 12 points) or placebo (6 +/- 12 points), whereas the last-mentioned two groups did not differ. Z-scores of Thai language and mathematics test results did not differ among the groups. We conclude that weekly iron supplementation is the regimen of choice in this study community.

Child↗

PubMed2001

Advances in the mass spectrometry of hemoglobin adducts: global analysis of the covalent binding of butadiene monoxide.

A common method to assess exposure to 1,3-butadiene through both occupational and environmental routes involves the detection of hemoglobin adducts formed by the primary reactive metabolite butadiene monoxide (EB). This assay is a modification of the Edman degradation procedure, which was developed to determine adducts formed specifically at the amine group of the N-terminal valine of hemoglobin. The goals of the current research are to determine the global modification of alpha- and beta-globin chains by EB and to localize the primary reactive residues to specific regions of the globin polypeptides. The degree of modification was monitored by electrospray mass spectrometry, which was used to measure the formation of EB-hemoglobin adducts (up to ten adducts per globin). Structural analysis of these modifications was performed by peptide mapping of globin peptides after trypsin digestion using liquid chromatography-mass spectrometry. These experiments provided information as to the relative reactivity of alpha- and beta-globin towards EB, as well as to the localization of adducts to specific peptide sequences. The results reveal variable reactivities of alpha- and beta-globin towards EB and also show the formation of multiple adducts at several alpha- and beta-globin sites. In addition, it is established that the N-terminal valine residues are not the first to be modified by EB.

Environmental Exposure↗

PubMed1975

Mössbauer investigations of high-spin ferrous heme proteins. II. Chloroperoxidase, horseradish peroxidase, and hemoglobin.

Reduced samples of chloroperoxidase, horseradish peroxidase, and deoxyhemoglobin were studied by Mössbauer spectroscopy in strong magnetic fields. The intricate paramagnetic spectra of chloroperoxidase were evaluated in detail in the framework of a spin Hamiltonian pertinent to high-spin ferrous iron. The studies strongly suggest that, in their reduced states, chloroperoxidase from Caldariomyces fumago and cytochrome P-450 from Pseudomonas putida have similar, if not identical ligand structures of the heme iron. The spectral similarities of these two proteins, noted in an earlier Mössbauer investigation, are further explored and substantiated. Reduced horseradish peroxidase and deoxyhemoglobin, on the other hand, show high-field Mössbauer spectra that differ considerably from each other and, in particular, from those of the P-450 type, suggesting a different ligand arrangement of the heme iron for each case.

Bacterial Proteins↗

PubMed1986

Properties of chemically modified Ni(II)-Fe(II) hybrid hemoglobins. Ni(II) protoporphyrin IX as a model for a permanent deoxy-heme.

Chemical modifications, NES-Cys(beta 93), des-Arg(alpha 141), and both modifications on the same molecule, were made to Ni-Fe hybrid hemoglobins, and their effect on individual subunits was investigated by measuring oxygen equilibrium curves, the Fe(II)-N epsilon (His F8) stretching Raman lines, and light-absorption spectra. The oxygen equilibrium properties indicated that modified Ni-Fe hybrid hemoglobins remain good models for the corresponding deoxy ferrous hemoglobins, although K1, the dissociation equilibrium constant for the first oxygen to bind to hemoglobin, was decreased by the chemical modifications. Resonance Raman spectra of deoxy alpha 2 (Fe) beta 2 (Ni) and light-absorption spectra of deoxy alpha 2 (Ni) beta 2 (Fe), revealed that the state of alpha hemes in both hybrid hemoglobins underwent a transition from a deoxy-like state to an oxy-like state caused by these chemical modifications when K1 was about 3 mm Hg (1 mm Hg approximately 133.3 Pa). On the other hand, the state of beta hemes in hybrid hemoglobins was little affected, when K1 was larger than 1 mm Hg. Modified alpha 2 (Fe) beta 2 (Ni) gave a Hill coefficient greater than unity with a maximum of 1.4 when K1 was about 4 mm Hg. The two-state model predicts that the K1 value at the maximum Hill coefficient should be much larger than this value. For oxygen binding to unmodified alpha 2 (Ni) beta 2 (Fe), oxygen equilibrium data suggested no structural change, while the spectral data showed a structural change around Ni(II) protoporphyrin IX in the alpha subunits. A similar situation was encountered with modified alpha 2 (Ni) beta 2 (Fe), although K1 was decreased as a result of the structural changes induced by the modifications.

Ferrous Compounds↗

PubMed2001

Determination of the hemoglobin surface domains that react with cytochrome b5.

We have compared the photoinitiated electron-transfer (ET) reaction between cytochrome b(5) (b(5)) and zinc mesoporphyrin-substituted hemoglobin [(ZnM)Hb] and Hb variants in order to determine whether b(5) binds to the subunit surface of either or both Hb chains, or to sites which span the dimer--dimer interface. Because the dimer--dimer interface would be disrupted for monomers or alpha beta dimers, we studied the reaction of b(5) with alpha ZnM chains and (ZnM)Hb beta W37E, which exists as alpha beta dimers in solution. Triplet quenching titrations of the ZnHb proteins with Fe(3+)b(5) show that the binding affinity and ET rate constants for the alpha-chains are the same when they are incorporated into a Hb tetramer or dimer, or exist as monomers. Likewise, the parameters for beta-chains in tetramers and dimers differ minimally. In parallel, we have modified the surface of the Hb chains by neutralizing the heme propionates through the preparation of zinc deuterioporphyrin dimethyl ester hemoglobin, (ZnD-DME)Hb. The charge neutralization increases the ET rate constants 100-fold for the alpha-chains and 40-fold for the beta-chains (but has has little effect on the affinity of either chain type for b(5), similar to earlier results for myoglobin). Together, these results indicate that b(5) binds to sites at the subunit surface of each chain rather than to sites which span the dimer-dimer interface. The charge-neutralization results further suggest that b(5) binds over a broad area of the subunit face, but reacts only in a minority population of binding geometries.

Animals↗

PubMed1985

Homeostatic mechanisms in the utilization of exogenous iron in children recovering from severe malnutrition.

We evaluated the role of initial iron stores on iron accumulation during recovery from severe edematous protein-energy malnutrition in children. Twenty-six preschool children were divided in two groups according to their initial iron reserves, as estimated from serum ferritin concentration, using a cutoff criterion of 30 ng/ml. The low ferritin (LF) group had a mean serum ferritin level of 12 +/- 8 ng/dl, and the high ferritin (HF) group, 86 +/- 32 ng/dl. Both groups had similar degrees of malnutrition and of anemia, as defined by hemoglobin concentration. All children received an adequate therapeutic diet and 60 mg iron daily as ferrous sulfate. The recovery of biochemical and anthropometric indicators of nutritional status, as well as of hemoglobin concentration, was similar in both groups. On the contrary, the LF group showed a marked increase in serum ferritin concentration from the onset of treatment, whereas the HF group had a net decline in this parameter by 30 days, and a stable level thereafter. The difference in serum ferritin concentration between groups was maintained until day 60, and both groups ended the study (90 days) with similar levels. Estimation of the utilization of exogenous iron from changes in total-body iron during the first 60 days of recovery showed the LF group to retain an average of 9.3% of iron intake, whereas the HF group retained only 1.4%.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Hypochromic↗

PubMed1985

Epoxidation of styrene by hemoglobin and myoglobin. Transfer of oxidizing equivalents to the protein surface.

Methemoglobin and metmyoglobin catalyze the H2O2-dependent oxidation of styrene to styrene oxide and benzaldehyde. The formation of styrene oxide requires molecular oxygen as well as H2O2 but does not, as shown by inhibitor studies, involve the superoxide or hydroxyl radicals. Approximately 38, 67, and 78% of the oxygen in styrene oxide derives from 18O2 in the reactions catalyzed, respectively, by bovine hemoglobin, sperm whale myoglobin, and equine heart myoglobin, whereas 70, 55, and 35% of the oxygen can be shown to be derived from [18O]H2O2. However, a larger fraction of the epoxide oxygen than suggested by the labeling data (perhaps all) derives from molecular oxygen rather than H2O2 because the hemoproteins produce molecular oxygen from the peroxide. The epoxidation of styrene by methemoglobin gives equal amounts of the R and S enantiomers and, as shown by studies with trans-[1-2H]styrene, proceeds with partial (33%) loss of the olefin stereochemistry. The results are rationalized by H2O2-dependent formation of a protein radical that combines with molecular oxygen to give a protein-peroxy radical that oxidizes styrene.

Animals↗

PubMed2005

Postfabrication encapsulation of model protein drugs in a negatively thermosensitive hydrogel.

A postfabrication encapsulation technique was developed for loading model protein drugs into an intelligent and biodegradable hydrogel film, which exhibits negative thermosensitivity with a desirable phase transition temperature between refrigerator temperature and body temperature. The hydrogel comprises mainly poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) block copolymer, and oligo(lactide). The model proteins Hemoglobin and Bovine Serum Albumin were loaded into the hydrogel films by soaking the gels at 4 degrees C, at which the hydrogel film was swollen. The loaded drug was released gradually in PBS at 37 degrees C, where the hydrogel film was shrunken. Because the hydrogel is biodegradable, the loaded drug could be released completely. It is confirmed that proteins can, in their native structures, be included in the hydrogel via the present technique, as characterized by FTIR, Raman spectrum, UV/VIS spectrum, and circular dichroism spectrum. The highlight of our approach is avoidance of high temperatures and organic solvents in encapsulation, making it ideal for protein drug delivery systems.

Body Temperature↗

PubMed2005

Mild postnatal anemia: is it a problem?

Mild postnatal anemia is common. However, determination of postnatal hemoglobin level or iron supplementation are not routine in many obstetric units. This study was designed to evaluate the impact of mild postnatal anemia and iron supplementation on women. One hundred fifty women who had postnatal hemoglobin levels between 80 and 99 g/L were randomly assigned into two groups with iron tablets or placebo provided from the time of diagnosis until reassessment at 6 weeks. The patients' general well-being, hemoglobin levels, iron status, side effects, and compliance were assessed. One hundred twenty-two women returned for reassessment. Twelve (9.8%) of the 122 women recruited and four (3.2%) of 122 nonanemic matched controls complained of dizziness 2 days after delivery; the difference was statistically significant (chi2 test, p<0.05). At 6 weeks postpartum, significantly more women were anemic (chi2 test, p<0.05) and iron deficient (chi2 test, p<0.01) in the placebo group. The score of general well-being as assessed by a 4-point scale was significantly higher in the iron supplementation group (Mann-Whitney test, p<0.05). The amounts of drugs consumed in both groups were comparable and the incidences of side effects were similar.

Adult↗

PubMed1992

Effect of coprophagy on bioavailability of iron from plant foods fed to anemic rats.

Effects of coprophagy and coprophagy preventing device on iron bioavailability were evaluated in two experiments. In Experiment 1, rats were fed diets with FeSO4, spinach, bran cereal or cornmeal as the iron source. The rats in each diet group were fitted with collars, sham-collars or not fitted with collars (control). In Experiment 2, rats were fed diets with FeSO4 or green peas as the iron source and were fitted with collars, tail cups, sham-collars or not fitted with any device (control). Preventing coprophagy reduced hemoglobin regeneration efficiency (HRE) of rats fed bran cereal, green peas, spinach or cornmeal diets by 26 (P less than .05), 24(P less than .05), 22(P less than .05) and 11% (not significant), respectively. Preventing coprophagy in rats fed FeSO4 diet did not significantly reduce HRE. Sham-collaring reduced (P less than .05) HRE of rats fed the FeSO4 diet by 12 and 13% but did not significantly affect HRE in rats fed food iron sources. It was more convenient and effective to prevent coprophagy with collars than with tail cups. Differences in bioavailability between food and FeSO4 iron due to coprophagy may be explained based on two gastrointestinal nonheme iron pools, complexed and highly soluble.

Absorption↗

PubMed1992

Effect of bezafibrate and clofibric acid on the spectroscopic properties of the nitric oxide derivative of ferrous human hemoglobin.

The effect of bezafibrate (BZF) and clofibric acid (CFA) on the spectroscopic (EPR and absorbance) properties of the nitric oxide derivative of ferrous human hemoglobin (HbNO) has been investigated quantitatively. In the presence of BZF and CFA, the X-band EPR spectra and the absorption spectra in the Soret region of HbNO display the same basic characteristics described in the presence of inositol hexakisphosphate (IHP) and 2, 3-diphosphoglycerate (2,3-DPG). Next, in the presence of these allosteric effectors, the oxygen affinity for ferrous human hemoglobin (Hb) is reduced. These findings indicate that BZF and CFA, as already reported for IHP and 2, 3-DPG, induce the stabilization of a low affinity conformation of the ligated hemoprotein (i.e., HbNO). Values of the apparent equilibrium constant for BZF and CFA binding to HbNO (K) are 1.5(+/- 0.2) x 10(-2) M and 2.8(+/- 0.3) x 10(-2) M, respectively, at pH 7.0 (in 0.1 M N-[2-hydroxyethyl]piperazine-N'-[2-ethanesulfonic acid]/NaOH buffer system plus 0.1 M NaCl) and 20 degrees C. The results reported here represent clearcut evidence for BZF and CFA specific (i.e., functionally relevant) binding to a ligated derivative of Hb (i.e., HbNO).

2,3-Diphosphoglycerate↗

PubMed2001

Randomized, controlled trial of single versus 3-times-daily ferrous sulfate drops for treatment of anemia.

OBJECTIVE: Adherence to treatment of iron-deficiency anemia often is poor in both developed and developing countries. The current standard therapy is ferrous sulfate drops (or syrup) administered 3 times daily. It is possible that adherence would improve with a single-dose daily treatment regimen. We compared the use of single versus 3-times-daily ferrous sulfate drops, at the same total iron dose, on treatment of anemia in infants. METHODS: To obtain a large enough cohort of anemic subjects, we performed the study in rural Ghana. Using a prospective, randomized, controlled design, we studied 557 anemic children (age range: 6-24 months; hemoglobin values: 70-99 g/L). One group (n = 280) received ferrous sulfate drops once daily (40 mg elemental iron), and the control group (n = 277) received ferrous sulfate drops 3 times per day (total dose, 40 mg elemental iron). Treatment lasted for 2 months. Hemoglobin and serum ferritin values were measured at baseline and at the end of the study. RESULTS: Successful treatment of anemia (hemoglobin >100 g/L) occurred in 61% of the single-dose and in 56% of the 3-times-daily group. Geometric mean ferritin levels increased significantly in each group from baseline to the final visit. Side effects were minimal and similar between the 2 groups. CONCLUSION: A single versus a 3-times-daily dose of ferrous sulfate drops over 2 months resulted in a similar rate of successful treatment of anemia, without side effects. To our knowledge, this is the first demonstration of the use of a single-dose daily regimen to treat anemia. Although not examined in the current study, use of a single-dose daily regimen may improve adherence to treatment of anemia in infants.

Anemia, Iron-Deficiency↗