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PubMed1997

Effectiveness of iron therapy on breath-holding spells.

OBJECTIVE: The objective of this study is to investigate the effect of iron therapy on breath-holding spells (BHS). METHODOLOGY: Sixty-seven children with BHS were enrolled in a clinical trial to evaluate the effect of iron therapy on BHS. At the beginning of therapy, the clinical, laboratory, and demographic characteristics of the patients in the treatment group (n = 33) and placebo group (n = 34) were comparable. Patients were assessed weekly for the first 8 weeks and then every 2 weeks for the next 8 weeks. Response to therapy was assessed by the change in the frequency of BHS. RESULTS: Children treated with iron showed significant reduction in the frequency of BHS (88%) compared with the frequency (6%) in the placebo group. As expected, the treated group showed a significant improvement of a number of blood indexes compared with the placebo group. Baseline mean levels of hemoglobin and total iron binding capacity were predictive of a favorable response to iron treatment. CONCLUSION: Results of this study indicate that iron therapy is effective in the treatment of BHS and that iron-deficient children seem to be more likely to benefit from such therapy. Response to iron therapy was strongly correlated with improvement in blood indexes.

Apnea↗

PubMed1994

[Treatment with prophylactic doses of ferrous sulphate as an intervention measure in the campaign++ against iron deficiency in children cared for in basic health units].

The efficacy of medical prophylaxis in the fight against iron deficiency anemia in 620 children aged from four to thirty-six months, attended in two health units of the municipality of S. Paulo, Brazil, was tested. First, the children's blood was tested for hemoglobin level and electrophoresis. Then they received daily doses of iron sulphate in the form of drops, corresponding to 12 mg/day of elementary iron, over a 30-day period. Afterwards, they were asked to return for re-evaluation. Twenty-five percent of children under 6 months presented hemoglobin levels under 11.0 g/dl. The highest occurrences of anemia were detected among children aged 9 to 11 months (49.5%) and in the age bracket between 12 and 23 months (50.4%). After the established period, only 37.4% of the children with anemia and 52.4% of children who did not present anaemia returned for further evaluation. Of the 299 evaluated, only 157 (52.5%) had taken the medication correctly. Frequency of hemoglobin inferior to 9.5 g/dl dropped from 17.1% at the beginning to 8.1% at the end of the intervention. On the other hand, the percentage of children with hemoglobin above 12.0 g/dl increased from 13.4% to 33.4%. Those children who took their iron supplements correctly registered a significantly higher drop in the number of cases of anemia than that observed in those who had not taken the supplement correctly. The great majority (80.3%) did not present any side effects of medication.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Hypochromic↗

PubMed1981

Bromobenzene epoxidation leading to binding on macromolecular protein sites.

Bromobenzene is metabolized via the hepatic mixed-function oxygenase system to reactive intermediates; i.e., 2,3- and 3,4-bromobenzene epoxides. These metabolites presumably bind to tissue macromolecules evoking cytotoxicity. However, the specific sites of macromolecular proteins are not known and this was investigated using microsomal protein and hemoglobin. The results indicate that 2,3- and 3,4-epoxide bind to macromolecules at different rates. The 3,4-epoxide is more reactive, binding covalently to microsomal protein at the site of its synthesis, whereas bromobenzene 2,3-epoxide is more stable, leaving the microsomal protein compartment and binding covalently to soluble protein, i.e., the hemoglobin beta chain. Structural analysis with fingerprint mapping of the hemoglobin beta chain after pretreatment with cysteine and histidine blocking agents such as p-nitrophenacyl bromide, 2-bromoethylamine hydrobromide and diethylprocarbonate indicated that the 2,3-epoxide preferentially binds to the cysteinyl residue, whereas the 3,4-epoxide binds to the histidinyl residue. This difference in binding of the 2,3- and 3,4-bromobenzene epoxides may be an important factor in determining the degree of their cytotoxicity.

Animals↗

PubMed1992

The effect of oral iron supplementation on erythropoiesis in autologous blood donors.

The effect of oral iron supplementation on erythropoiesis was studied prospectively in 34 autologous blood donors. The subjects, all of whom were to undergo total hip surgery, had normal iron status at the start of the study. During the preoperative period, in which 4 units of blood were collected, 17 patients received oral iron supplementation with 287 mg of ferrous sulfate (105 mg of elemental iron/day), while 17 patients did not use any iron supplementation. Oral iron supplementation during the 4-week preoperative period lessened the decrease in ferritin levels after two phlebotomies. Neither the decrease in hemoglobin nor the increase in erythropoietin levels was influenced by iron supplementation. In both iron-supplemented and control patients, serum erythropoietin levels returned to initial values within a few days after surgery. In autologous blood donors with a normal iron status, the use of supplemental iron does not affect erythropoiesis and is insufficient to maintain iron stores.

Administration, Oral↗

PubMed1983

In vivo function of hemolysin in the nephropathogenicity of Escherichia coli.

The role of hemolysin in the nephropathogenicity of Escherichia coli was studied in a hematogenous pyelonephritis model in mice. The nephropathogenicity of a nonhemolytic, avirulent E. coli strain was increased by simultaneous injection with its hemolytic, nephropathogenic parent. This helper mechanism could be attributed to hemolysin, since the simultaneous injection of partially purified hemolysin gave a similar enhancement of nephropathogenicity. Intraperitoneal injection of hemoglobin or iron sulfate before intravenous challenge with this avirulent strain also led to increased virulence. The nephropathogenicity-enhancing effect of hemolysin is therefore supposed to depend on increasing the level of available iron in the host. Under conditions of plentiful iron, hemolysin production was repressed, as shown by in vitro growth experiments in the presence of exogenous iron. These results suggest that the production of hemolysin is regulated by feedback inhibition.

Animals↗

PubMed1989

[The influence of green tea upon the improvement of iron deficiency anemia with pregnancy treated by sodium ferrous citrate].

Green tea is indispensable to our everyday life. In Japan it has long been common knowledge that the ingestion of green tea should be avoided before and after the intake of iron preparations. There have recently been some reports, however, that deny the effect of green tea on iron preparations. A study was conducted on pregnant patients with anemia, using sodium ferrous citrate (Ferromia). The drug was administered to a group of patients taking green tea and a group taking water. Our results can be summarized as follows. 1. Hemoglobin, serum iron and total iron binding capacity were markedly improved after the administration of the iron preparation, and there was no difference between these parameters in the two groups of patients. 2. There was a tendency for patients with hypochromia to show a more marked improvement in hemoglobin in both groups. 3. Anemia cured in 96.7% of patients in the green tea group and in 93.4% of patients in the water group after the oral administration of the iron preparation. 4. The incidence of side effects stood at 18.3% for the green tea group and 21.9% for the water group, there being no significant difference. No serious side effects were elicited in the present study.

Adult↗

PubMed1978

[Treatment of iron deficiency anemia with ferrosulfate serin komplex (author's transl)].

The results of treatment of iron deficiency anemia in 217 children and infants (aged 8 months to 12 years) with ferrosulfate serin complex are demonstrated: 208 children with simple iron deficiency anemia with hemoglobin 9.1 g/100 ml before treatment had in the first 4 weeks a daily increase of 0.082 g/10000 ml hemoglobin; in 3 children with severe anemia of chronic blood loss the daily increase was 0.21 mg/100 ml and in 6 children with hypoxic polycythemia with congenital heart disease and so called latent iron deficiency anemia the increse was 0.16 g/100 ml. Through the better absorption of this serin-ferrosulfate complex the required dosis is only 3 mg/kg/d. The benefit of this small dosis is the low rate of side effects.

Anemia, Hypochromic↗

PubMedDate not supplied

Changes in iron status during competitive season in female collegiate swimmers.

We examined changes in iron status in 25 female varsity collegiate swimmers over the course of a competitive season via weekly capillary blood sampling. We also studied the effectiveness of moderate iron supplementation (39 mg/day) in preventing expected changes in iron status via a double-blinded crossover design. On entry into the study, 17 of the swimmers had depleted iron stores (plasma ferritin < 12 micrograms/L) and 5 were anemic (Hb < 120 g/L). After 5 wk of placebo treatment, hemoglobin decreased (> or = 6 g/L) in 44% and increased in 12% of the subjects. After 5 wk of iron supplementation, hemoglobin decreased in 16% and increased in 24% of the subjects. Likewise, after placebo treatment, plasma ferritin decreased (> or = 5 micrograms/L) in 24% and increased in 4% of the subjects, whereas iron supplementation resulted in decreases in 4% and increases in 68% of the subjects. In the absence of iron supplementation, hemoglobin levels decreased despite mean dietary iron intakes of 16.3 mg/day. These results show that moderate iron supplementation is effective in preventing decline in the iron status of female collegiate swimmers during a competitive season, but a higher dose of iron may be necessary to reverse their iron-deficient state.

Adolescent↗

PubMed2005

Nature of the FeO2 bonding in myoglobin and hemoglobin: A new molecular paradigm.

The iron(II)-dioxygen bond in myoglobin and hemoglobin is a subject of wide interest. Studies range from examinations of physical-chemical properties dependent on its electronic structure, to investigations of the stability as a function of oxygen supply. Among these, stability properties are of particular importance in vivo. Like all known dioxygen carriers synthesized so far with transition metals, the oxygenated forms of myoglobin and hemoglobin are known to be oxidized easily to their ferric met-forms, which cannot bind molecular oxygen and are therefore physiologically inactive. The mechanistic details of this autoxidation reaction, which are of clinical, as well as of physical-chemical, interest, have long been investigated by a number of authors, but a full understanding of the heme oxidation has not been reached so far. Recent kinetic and thermodynamic studies of the stability of oxymyoglobin (MbO2) and oxyhemoglobin (HbO2) have revealed new features in the FeO2 bonding. In vivo, the iron center is always subject to a nucleophilic attack of the water molecule or hydroxyl ion, which can enter the heme pocket from the surrounding solvent and thereby irreversibly displace the bound dioxygen from MbO2 or HbO2 in the form of O2- so that the iron is converted to the ferric met-form. Since the autoxidation reaction of MbO2 or HbO2 proceeds through a nucleophilic displacement following one-electron transfer from iron(II) to the bound O2, this reaction may be viewed as a meeting point of the stabilization and the activation of molecular oxygen performed by hemoproteins. Along with these lines of evidence, we finally discuss the stability property of human HbO2 and provide with the most recent state of hemoglobin research. The HbA molecule contains two types of alphabeta contacts and seems to differentiate them quite properly for its functional properties. The alpha1beta2 or alpha2beta1 contact is associated with the cooperative oxygen binding, whereas the alpha1beta1 or alpha2beta2 contact is used for controlling the stability of the bound O2. We can thus form a unified picture for hemoglobin function by closely integrating the cooperative and the stable binding of molecular oxygen with iron(II) in aqueous solvent. These new views on the nature of FeO2 bonding and the possible role of globin moiety in stabilizing MbO2 and HbO2 are of primary importance, not only for a full understanding of various hemoprotein reactions with O2, but also for planning new molecular designs for synthetic oxygen carriers which may be able to function in aqueous solvent and at physiological temperature.

Binding Sites↗

PubMed1987

Assessment of the alpha 1 beta 2 contact structure of valency hybrid hemoglobins by ultraviolet difference spectra.

We have developed a rapid and useful method for purification of valency hybrid hemoglobins (alpha 2+ beta 2 and alpha 2 beta 2+: + denotes ferric heme) from a hemoglobin solution oxidized partially with ferricyanide by preparative high-performance liquid chromatography. This method does not involve the separation of hemoglobin subunits and the reconstitution of ferric and partner ferrous subunits. Using the valency hybrid hemoglobins thus prepared, the effect of the ferric spin state on the alpha 1 beta 2 subunit boundary structure was investigated by measuring the ultraviolet difference absorption spectra between the deoxy and the oxy valency hybrids associated with various ferric ligands (fluoride, aquo, azide and cyanide). All derivatives of both alpha 2+ beta 2 and alpha 2 beta 2+ showed the difference spectra characteristic of R-T quaternary structural transition. However, the magnitude of the difference spectral peak observed near 288 nm was larger for high-spin derivatives than for low-spin ones. The magnitude of the peak for the valency hybrid hemoglobin was closely correlated with the difference in the free energy of oxygen binding between the R and T states. Since the R state of high-spin hybrids is considered to be identical to that of low-spin hybrids, we concluded from these results that the alpha 1 beta 2 subunit boundary structure plays an important role in regulating the oxygen affinity of deoxy T state.

Allosteric Regulation↗

PubMed1964

PRELIMINARY REPORT ON AN IRON-SORBITOL-CITRIC ACID COMPLEX (JECTOFER), A NEW INTRAMUSCULAR IRON PREPARATION.

One hundred and twenty-eight patients with iron deficiency anemia were treated with a new intramuscular iron preparation, iron-sorbitol-citric acid. One group of 10 patients received a total of 1000 mg. each of elemental iron intramuscularly. All obtained a rise in hemoglobin of over 2.1 g. %, an elevation of serum iron, and a reticulocyte response over 6%. A second larger group of subjects consisted of 113 prenatal and five gynecologic patients; these received an average total dose of 1050 mg. and 1020 mg., respectively, and the average increase in hemoglobin ranged from 1.6 g. % to 2.5 g. %.None of the patients developed significant side effects after injection or permanent staining at the site of injection. Three patients experienced a transient ache at the injection site, and three developed local urticaria-like reactions lasting 24 hours.This new preparation appears to be a safe and clinically effective therapeutic agent in situations in which parenteral iron is indicated.

Anemia↗

PubMed2003

Surface grafting of glycidyl methacrylate on silica gel and polyethylene beads.

Surface grafting of glycidyl methacrylate (GMA) on silica gel and a polyethylene bead was performed by radical polymerization and radiation-induced polymerization, respectively, in order to improve softness. Subsequently, diethylene triamine (DETA), triethylene tetraamine (TETA), and iminodiacetic acid (IDA) were introduced to the grafted GMA for use as affinity columns. The efficiency of the affinity column was investigated by use of bovine serum albumin (BSA) and hemoglobin (Hb) as model proteins. The affinity degree of BSA was higher than Hb for the DETA and TETA column, whereas the affinity degree of Hb was higher than BSA for the IDA column supported by silica gel. The affinity degree of BSA was higher than Hb for the DETA and TTA column supported by polyethylene (PE) beads.

Amines↗

PubMed2006

Clinical inquiries. What is appropriate management of iron deficiency for young children?

Infants and toddlers with suspected iron-deficiency anemia should begin treatment with oral ferrous sulfate (3 mg/kg/d of elemental iron). A rise in hemoglobin >1 g/dL after 4 weeks supports the diagnosis of iron deficiency, and supplementation should continue for 2 additional months to replenish iron stores. Recheck hemoglobin at the end of treatment and again 6 months later (strength of recommendation [SOR]: C, based on expert opinion). For primary prevention, counsel parents on the use of iron-fortified formula for non-breastfed infants until the age 12 months (SOR: B, based on randomized controlled study), and introduce iron-rich foods between 4 and 6 months to breastfed babies (SOR: C, based on expert opinion).

Administration, Oral↗

PubMed2001

Oral versus intravenous iron supplementation in peritoneal dialysis patients.

The vast majority of erythropoietin (EPO)-treated peritoneal dialysis (PD) patients require iron supplementation. Most authors and clinical practice guidelines recommend primary oral iron supplementation in PD patients because it is more practical and less expensive. However, numerous studies have clearly demonstrated that oral iron therapy is unable to maintain EPO-treated PD patients in positive iron balance. Once patients become iron-deficient, intravenous iron administration has been found to more effectively augment iron stores and hematologic response than does oral therapy. We recently performed a prospective, cross-over trial in 28 iron-replete PD patients and showed that twice-monthly outpatient iron polymaltose infusions (200 mg) were a practical and safe alternative to oral iron. That treatment produced significant increases in hemoglobin concentration and body iron stores. The additional expense of intravenous iron therapy was completely offset by reductions in EPO dosage. Careful monitoring of iron stores is important in patients receiving intravenous iron supplementation in view of epidemiologic links with infection and cardiovascular disease. Nevertheless, a growing body of evidence suggests that, as has been found for hemodialysis patients, intravenous iron therapy is superior to oral iron supplementation in EPO-treated PD patients.

Administration, Oral↗

PubMed1999

Acute and long-term stability studies of deoxy hemoglobin and characterization of ascorbate-induced modifications.

The reaction of ascorbate with recombinant hemoglobin (rHb1.1) in the presence of differing partial pressures of oxygen was studied. In the presence of 15 000 ppm (1.5%) residual oxygen, ascorbate/oxygen-mediated reactions resulted in an increased rate of autoxidation, modification of the beta-globin, increased oxygen affinity and decreased maximum Hill coefficient. One of the observed modifications to the beta-globin was a 72 Da addition to its N-terminus. Detailed characterization indicates the modification was an imidazolidinone type structure. Thorough deoxygenation of the hemoglobin solution to <150 ppm of oxygen prior to addition of ascorbate was required to prevent these modifications. Addition of ascorbate to the deoxy hemoglobin (deoxyHb) at pH 8 induced aggregation, eventually leading to precipitation. No such precipitation was observed at pH 7. Long-term storage of the hemoglobin was carried out by addition of ascorbate to deoxyHb at pH 7. The level of methemoglobin remained at <2% for up to 1 year at 4 degreesC, with no detectable precipitation of the protein. Modifications similar to those observed by the acute studies were observed over the 1-year period and correlated with disappearance of the added ascorbate.

Ascorbic Acid↗

PubMed2000

Impact of siderophore production on Pseudomonas aeruginosa infections in immunosuppressed mice.

Pseudomonas aeruginosa produces siderophores, pyoverdin and pyochelin, for high-affinity iron uptake. To investigate their contribution to P. aeruginosa infections, we constructed allelic exchange mutants from strain PAO1 which were deficient in producing one or both of the siderophores. When inoculated into the calf muscles of immunosuppressed mice, pyochelin-deficient and pyoverdin-deficient mutants grew and killed the animals as efficiently as PAO1. In contrast, the pyochelin- and pyoverdin-deficient (double) mutant did not show lethal virulence, although it did infect the muscles. On the other hand, when inoculated intranasally, all mutants grew in the lungs and killed immunosuppressed mice. Compared with PAO1, however, the pyoverdin-deficient mutant and the double mutant grew poorly in the lungs, and the latter was significantly attenuated for virulence. Irrespective of the inoculation route, the pyoverdin-deficient and doubly deficient mutants detected in the blood were significantly less numerous than PAO1. Additionally, in vitro examination demonstrated that the growth of the double mutant was extremely reduced under a free-iron-restricted condition with apotransferrin but that the growth reduction was completely canceled by supplementation with hemoglobin as a heme source. These results suggest that both pyoverdin and pyochelin are required for efficient bacterial growth and full expression of virulence in P. aeruginosa infection, although pyoverdin may be comparatively more important for bacterial growth and dissemination. However, the siderophores were not always required for infection. It is possible that non-siderophore-mediated iron acquisition, such as via heme uptake, might also play an important role in P. aeruginosa infections.

ATP-Binding Cassette Transporters↗

PubMed1989

Protective effect of sucrose on spray drying of oxyhemoglobin.

As far as we know, spray drying has previously not been applied to oxyhemoglobin, undoubtedly because of the sensitivity of oxyhemoglobin to temperature and oxidation. Our experience with freeze drying encouraged us to perform spray-drying trials in order to compare the results of the two methods, in the absence and the presence of protective compounds. Spray drying of hemoglobin without a protective compound led, as in freeze drying, to formation of a percentage of methemoglobin (50%) that makes it unsuitable for transporting oxygen. In the presence of 0.25 M sucrose (optimum) and at 80-100 degrees C, the functional properties of the hemoglobin were well preserved (methemoglobin approximately 4%), and the residual humidity was limited to approximately 3%. Structural investigation by optical circular dichroism confirmed the results obtained by freeze drying: in the presence of an effective protector, the spectra were similar to those of control hemoglobin and the immediate environment of the heme did not undergo any major change. Electron spin resonance absorption bands in all samples were similar for each value of the spectral decomposition factor, g. This suggests that the structure of the heme is not altered by desiccation and that the protector does not penetrate into the heme pocket since it would have disturbed the symmetry of the crystalline field. Fundamentally, these results are equivalent or similar to those observed with freeze drying; since spray drying is a different process of dehydration, the results indicate a lack of specificity in the phenomena of oxidation or of protection affecting hemoglobin.

Chemistry, Pharmaceutical↗

PubMed2003

Comparison of response between food supplemented with powdered iron and iron in syrup form for iron deficiency anemia.

OBJECTIVE: To evaluate and compare the response between food supplemented with iron in powdered and iron in syrup forms for the treatment of iron deficiency anemia in children aged 1-5 years. DESIGN: Quasi-experimental study. PLACE AND DURATION OF STUDY: This study was conducted at Combined Military Hospital, Multan, from January 2000 to December 2000. PATIENTS AND METHODS: Consecutive 200 cases of iron deficiency anemia, aged 1-5 years, were included in the study. Diagnosis was based on history, physical examination, complete blood counts (CBC) and serum ferritin levels. The patients were randomized to receive either iron in syrup form (Group A) or equivalent doses of iron powder sprinkled over food (Group B). The patients were followed up with hemoglobin estimation (Hb) and reticulocyte response at 2 weeks, 4 weeks and 6 weeks. CBC and serum ferritin were repeated at 6 weeks. RESULTS: Over half (51%) of the patients were between 1-2 years of age. One hundred thirty-two were males and 68 females. Most of the patients belonged to poor socioeconomic class. The iron in powder form was better tolerated than iron syrup as this group witnessed fewer episodes of gastrointestinal disturbances. The rise in mean Hb level after 6 weeks of treatment in group A and B was 1.6 g/dl and 1.9 g/dl respectively. Hemoglobin rise in group B was more than group A but this was statistically non-significant (p > 0.05). There was small but significant (p < 0.05) rise in serum ferritin in both the groups. There was no significant difference between the two groups for response to the two forms of iron administration. CONCLUSION: The powdered form of iron is a cost-effective and better tolerated method of iron administration in children and can be considered as an alternate option for the treatment of iron deficiency anemia in children.

Administration, Oral↗