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PubMed1983

Iron deficiency and sickle cell anemia.

In a patient with sickle cell anemia, iron deficiency was accompanied by hypochromic, microcytic RBCs, absence of bone marrow iron, and a low serum ferritin level. The mean corpuscular hemoglobin concentration (MCHC) was decreased (27.6 g/dL) and was associated with an extreme scarcity of sickled erythrocytes in blood smears. Iron therapy resulted in reticulocytosis and an increase in sickled erythrocytes. In vitro studies demonstrated a decrease in sickling of erythrocytes as a function of oxygen saturation of the blood when the patient was iron deficient. The whole blood oxygen dissociation curve showed a substantial decrease in oxygen pressure necessary to produce 50% saturation of hemoglobin at pH 7.4 and 37 degrees C (P50), indicating an increased oxygen affinity. These data suggest that a reduction of the MCHC induced by iron deficiency may ameliorate sickling.

Anemia, Hypochromic↗
PubMed2004

Effects of separate delivery of zinc or zinc and vitamin A on hemoglobin response, growth, and diarrhea in young Peruvian children receiving iron therapy for anemia.

INTRODUCTION: Anemia is the most prevalent nutritional deficiency in the world. Attempts to improve iron indexes are affected by deficiency of and interaction between other micronutrients. OBJECTIVE: Our goal was to assess whether zinc added to iron treatment alone or with vitamin A improves iron indexes and affects diarrheal episodes. DESIGN: This was a randomized, placebo-controlled, double-blind trial conducted in Peru. Anemic children aged 6-35 mo were assigned to 3 treatment groups: ferrous sulfate (FS; n = 104), ferrous sulfate and zinc sulfate (FSZn; n = 109), and ferrous sulfate, zinc sulfate, and vitamin A (FSZnA; n = 110). Vitamin A or its placebo was supplied only once; iron and zinc were provided under supervision >/=1 h apart 6 d/wk for 18 wk. RESULTS: The prevalence of anemia was 42.97%. The increase in hemoglobin in the FS group (19.5 g/L) was significantly less than that in the other 2 groups (24.0 and 23.8 g/L in the FSZn and FSZnA groups, respectively). The increase in serum ferritin in the FS group (24.5 mug/L) was significantly less than that in the other 2 groups (33.0 and 30.8 mug/L in the FSZn and FSZnA groups, respectively). The median duration of diarrhea and the mean number of stools per day was significantly higher in the FS group than in other 2 groups (P < 0.005). CONCLUSION: Adding zinc to iron treatment increases hemoglobin response, improves iron indexes, and has positive effects on diarrhea. No additional effect of vitamin A was found.

Anemia, Iron-Deficiency↗
PubMed2007

An investigation of the peroxidase activity of Vitreoscilla hemoglobin.

In order to investigate the ability of the Vitreoscilla hemoglobin (VHb) to act as a peroxidase, the protein was overexpressed in Escerichia coli and purified using a 6xHis-tag. The peroxidase activity of VHb was studied using 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferrocene carboxylic acid (FcCOOH) dopamine and L-dopa as substrates. The effects of external agents such as pH, salt concentration/ionic strength, and the thermal stability of VHb on the catalytic activity were assessed. The optimum pH for VHb using ABTS as a substrate was estimated to be 6-7. The VHb protein proved to be stable up to 80 degrees C, as judged by its peroxidase activity. Furthermore, NaCl concentrations up to 100 mM did not exert any significant effect on the activity. The catalytic activity against ABTS and FcCOOH was similar to that measured for horseradish peroxidase, whereas in the case of the phenolic substrates dopamine and L-dopa the activity was several orders of magnitude lower. The Michaelis constants, KmH2O2, were in good agreement with the data for human and bovine hemoglobin. No activity could be detected for the negative controls lacking VHb. These results demonstrate that VHb exhibits peroxidase activity, a finding in line with the hypothesis that VHb has cellular functions beyond the role as an oxygen carrier.

Bacterial Proteins↗
PubMed1992

Structural study and preliminary crystallographic data for the hemoglobin from reindeer (Rangifer tarandus tarandus)

The ferric form of reindeer hemoglobin (Rangifer tarandus tarandus) has been crystallized in an orthorhombic crystalline form from polyethylene glycol solutions, at pH 8.2. The crystals belong to the orthorhombic space group P2(1)2(1)2(1), with unit cell edges a = 84.2 A, b = 59.9 A, c = 119.5 A; one hemoglobin tetramer is contained in the asymmetric unit. The crystals diffract X-rays to a limit spacing of 3.0 A. Inspection of amino acid sequences in the N-terminal region of beta-chains, and analysis of hemoglobin three-dimensional models, allows one to rationalize, on a molecular basis, the reduced O2 affinity and the decreased effect of organic phosphates observed in ruminant hemoglobins. By analogy, the analysis is extended to birds and reptiles, whose hemoglobin beta-chains display, as in ruminants, the deletion of the N-terminal residue and a methionine at the NA2 position.

2,3-Diphosphoglycerate↗
PubMed1997

Markers of masked iron deficiency and effectiveness of EPO therapy in chronic renal failure.

Recombinant erythropoietin (rHuEPO) is well established in the management of anemia of chronic renal disease. However, a number of clinical issues, including the best laboratory indicators of an imminent marrow response to rHuEPO replacement, the ideal measurements to detect masked iron deficiency, and optimal methods of iron replacement, remain unanswered. To investigate these issues, studies were performed in anemic chronic hemodialysis patients. A number of standard hematologic measurements in addition to automated reticulocyte counts (Sysmex R-1000) and serum transferrin receptors (TfR) were obtained in these patients. A response to initiation of rHuEPO administration could be predicted if the serum TfR concentration was less than 6 mg/L (normal, 3.8 to 8.5 mg/L). In patients on rHuEPO, an imminent hemoglobin response to an increased rHuEPO dose could be predicted after 1 week based on a greater than 20% increase from baseline in the serum TfR or absolute reticulocyte count, with a sensitivity of 92%. In patients on rHuEPO replacement with serum ferritin levels greater than 30 microg/L, none of the panel of tests, including serum TfR, reliably detected masked iron deficiency. In a long-term study over 5 months in patients on a stable maintenance dose of EPO, a gradual decline in total body iron occurred, even in subjects with initial adequate iron stores, and despite taking 50 mg elemental iron daily as oral ferrous sulphate. The serum TfR is useful for predicting a hemoglobin response when initiating rHuEPO therapy, and combined with automated reticulocyte counting it is valuable for predicting a hemoglobin response when increasing the dose of rHuEPO. The serum TfR loses its specificity for detecting tissue iron deficiency in patients on maintenance rHuEPO therapy because of increased erythropoiesis, which itself raises serum TfR levels.

Adult↗
PubMed1983

The effects of three different regimens of oral contraceptives and three different intrauterine devices on the levels of hemoglobin, serum iron and iron binding capacity in anemic women.

The effects on hemoglobin, iron and iron binding capacity (IBC) in 150 moderately anemic women of 1) a 21-day low-dose combined pill, 2) the same low-dose combined pill for 21 days, followed by 7 days of an iron-containing pill, 3) the same low-dose combined pill administered for 63 consecutive days, followed by 7 days of no pill intake, 4) Lippes IUD, 5) TCu 220C and 6) Progestasert were studied. The three pill regimens were associated with an increase in hemoglobin and serum iron after 12 months. However, the iron pill and 63-day schedule groups produced an increase in hemoglobin and iron at the 6th month ans a diminution of IBC at 12 months. The Lippes and TCu 220C groups did not show any change in hemoglobin, iron or iron binding capacity after 12 months. The Progestasert group showed an increase in hemoglobin and iron levels at 6 and 12 months, and a diminution of IBC at 12 months. The pill and Progestasert have advantages as contraceptives in anemic women.

Adolescent↗
PubMed1992

Stabilized hemoglobins as acellular resuscitative fluids.

This study reports some recent work dealing with the stabilization of the tetramers of hemoglobin. It is shown that by using a variety of diacids, it is possible to increase the P50 above that of stroma free hemoglobin. In order to lengthen the retention times in the circulatory system, the stabilized hemoglobins were complexed with both hydroxyethyl starch polymers and polyol tetronic polymers. The resulting hemoglobin-polymer compounds were then freeze-dried. It was possible to reconstitute the powder by the addition of physiological saline when needed. The methods presented here appear to be appear to be as effective as using pyridoxal phosphate but at a fraction of the cost.

Animals↗
PubMed2000

Protease activity of CND41, a chloroplast nucleoid DNA-binding protein, isolated from cultured tobacco cells.

CND41 is a 41 kDa DNA-binding protein isolated from chloroplast nucleoids of cultured tobacco cells. The presence of the active domain of aspartic protease in the deduced amino acid sequence of CND41 suggests that it has proteolytic activity. To confirm this, CND41 was highly purified from cultured tobacco cells and its proteolytic activity was characterized with fluorescein isothiocyanate-labeled hemoglobin as the substrate. The purified CND41 had strong proteolytic activity at an acidic pH (pH 2-4). This activity was inhibited by various chemicals, including the nucleoside triphosphates, NADPH, Fe(3+) and sodium dodecyl sulfate.

Adenosine Triphosphate↗
PubMed1983

Bioavailability of egg yolk iron measured by hemoglobin regeneration in anemic rats.

Biological availability of egg yolk iron and effect of egg yolk on absorption of iron from the reference salt, ferrous sulfate, were evaluated in hemoglobin repletion assays with anemic rats. Three measures of response, hemoglobin concentration, gain in hemoglobin iron content, and gain in carcass iron content were related to total dietary iron intake by regression analyses. Relative biological value (RBV) of yolk iron, in diets without ascorbic acid, compared to that of the reference salt was 85%. RBV of egg iron was equivalent to ferrous sulfate iron in diets containing 1 g ascorbic acid per kilogram of diet. Increasing increments of egg yolk in diets containing ascorbic acid had no significant effect on utilization of iron from the reference salt as measured by gain in hemoglobin or carcass iron content during the regeneration period. Stimulation of iron utilization from egg yolk by ascorbic acid was mild in these studies and was less in diets containing 32 mg/kg of egg yolk iron than in those containing 15 mg/kg of iron from egg.

Absorption↗
PubMedDate not supplied

Treatment of iron deficiency anemia and associated protein-losing enteropathy in children.

PURPOSE: The aims of this study were to evaluate the response of oral iron treatment in children with iron deficiency anemia (IDA) fed whole cow's milk (WCM) or soy formula; to compare the incidence of fecal blood loss in infants fed WCM and soy formula; and to evaluate the incidence and relation of protein-losing enteropathy (PLE) and IDA by testing serum albumin, fecal blood loss, and fecal alpha1-antitrypsin (alpha1AT). METHODS: Twenty-four children with nutritional IDA were randomly assigned to receive either 16 oz WCM or soy formula daily. Both groups were treated with daily therapeutic oral iron during 12 weeks. Stool specimens for hemoglobin losses were collected at weeks 0, 3, 6, and 12. Levels of serum albumin and fecal alpha1AT were tested at diagnosis and when IDA was corrected. RESULTS: Anemia was corrected in 21 of the 24 children by week 6 or 12. Median fecal hemoglobin losses were not increased in either group at diagnosis or during treatment. Seven of 24 children had PLE at diagnosis with elevated fecal alpha1AT levels of 72 to 381 mg/dL that returned to normal after correction of IDA. Their initial fecal alpha1AT levels averaged 170 mg/ dL at diagnosis and 21 mg/dL after the IDA was corrected. Excessive WCM intake of 30 oz/day or more was present in 63% of the infants. CONCLUSIONS: Treatment of nutritional IDA with oral iron was just as effective with a limited quantity of either WCM or soy formula. Fecal hemoglobin losses were uncommon and did not differ in children at diagnosis or during treatment of IDA. PLE associated with IDA resolves when the IDA is corrected, but differences between children fed WCM or soy formula could not be detected.

Anemia, Iron-Deficiency↗
PubMed1978

Tertiary structure variability within the quaternary states of hemoglobin: a spin label study.

Using variable temperature techniques, the spin label spectral resolution of hemoglobin labeled at the beta93 cysteines with N-(1-oxyl-2,2,6,6-tetramethyl-4-piperidinyl)iodonacetamide has been greatly enhanced. The effects of different ligands, inositol hexaphosphate, pH and salt concentration upon spin labeled ferrous and ferric hemoglobin indicate that the beta chain tertiary structure exhibits considerable variability within the oxy and deoxy quaternary structures. From these studies ligand and spin state changes both appear to be of significance in producing structural changes; binding of inositol hexaphosphate then produces further structural changes secondary in amplitude.

Chemical Phenomena↗
PubMed2005

Sodium ferric gluconate for post-transplant anemia in pediatric and young adult renal transplant recipients.

Post-transplant anemia is a widespread problem among pediatric renal transplant recipients. Many clinicians treat post-transplant anemia in a manner similar to treatment of anemia in dialysis patients, including the use of intravenous iron, such as sodium ferric gluconate (SFG). Data on pediatric dosing of SFG are limited to rare small series containing few or no renal transplant recipients. We conducted a retrospective chart review of practice patterns at our institution to evaluate doses used, hemoglobin response and adverse events. We identified 15 renal transplant recipients who received SFG during the 28-month study period. Data from 14 of these patients were available for analysis. Patients received between one and six doses of SFG to yield a total dose of 100-1000 mg or 2.7-23.7 mg/kg. The largest doses given during a single infusion ranged from 1.9 to 6.4 mg/kg. The mean hemoglobin level increased from 101 +/- 16 to 114 +/- 21 g/L (p = 0.0092) following SFG therapy. Adverse events were recorded for three patients. Treatment with SFG appears to yield some improvement in anemia in renal transplant recipients, but the paucity of published information on this topic highlights the need for stronger data, particularly with respect to pediatric patients.

Adolescent↗
PubMed2007

When to start supplementary iron to prevent iron deficiency in early childhood in sub-Saharan Africa setting.

BACKGROUND: To study the efficacy of oral ferrous fumarate, an inexpensive, readily available preparation on iron deficiency in infants in Africa. PROCEDURE: Four months old (group 1, n = 252) and 6-18 months old (group 2, n = 360) healthy infants attending four primary health care centers (PHC) for vaccination/well-child visits in Benin were studied. Ninety-six pregnant women (PW) over 36 weeks gestational age attending the same PHC during the study period were also studied. Infants were offered 2 months supplementation with oral powdered generic ferrous fumarate (GFF), that is, 5 mg/kg/day of elemental iron, given twice and were reevaluated 2 months later for hematological indices. The prevalence of anemia and iron deficiency among pregnant women was assessed using hematological indices and transferrin saturation. RESULTS: The prevalence of anemia was 42.0%, 61.9%, and 37.5% in groups 1, 2, and PW, respectively. All anemic PW were iron deficient. Hemoglobin level shifted towards high values after supplementation. In addition, 24 infants from group 1 whose mothers interrupted the treatment, showed a significant decrease in hemoglobin level values, and similar improvement after two additional months of supplementation. CONCLUSION: Programs to prevent iron deficiency in Africa should utilize inexpensive preparations, start during pregnancy, continue in infants at 3 months of age and address problems of noncompliance.

Administration, Oral↗
PubMed2002

Exposure-dependent accumulation of N-(2-hydroxypropyl)valine in hemoglobin of F344 rats exposed to propylene oxide by the inhalation route.

The detection of hemoglobin adducts by mass spectrometry is a very sensitive and specific measurement of the extent of covalent binding of electrophilic chemicals. The exposure-dependent accumulation of N-(2-hydroxypropyl)valine (N-HPVal) in globin of rats exposed to propylene oxide (PO) (0, 5, 25, 50, 300 or 500 ppm) by the inhalation route was measured to assess the utility of Hb adducts as biomarkers of exposure. Analysis of N-HPVal by gas-chromatography tandem mass spectrometry showed a linear exposure-dependent response for adduct accumulation in globin of rats exposed to PO for 3 days (6 h/day). After 20 days of exposure (6 h/day; 5 days/week), the exposure-response curve was slightly sub-linear. DNA adducts had been measured in several organs of the same animals in a companion study. The dose-response for accumulation of DNA adducts was similar to that obtained for Hb adducts. However, the number of DNA adducts varied by 17-fold between different tissues. The highest number of DNA adducts was found in respiratory nasal tissue, followed by lung and then liver. These data demonstrate that hemoglobin adducts provide a sensitive dosimeter for systemic exposure, but cannot be used to predict the extent of DNA binding in individual tissues. Furthermore, the exposure-response curve for both hemoglobin and DNA adduct accumulation does not reflect the tumor incidence curve for PO, providing evidence that the assessment of risk to cancer is more complex than simple biomarker measurements. When the present rat data were compared with recent N-HPVal measurements in humans, similar binding was found.

Animals↗
PubMed2002

Increased release of free Fe ions in human erythrocytes during aging in the circulation.

We investigated whether free Fe ions were released in erythrocytes during aging process in the circulation. Young and senescent erythrocytes were separated from freshly drawn human blood by Percoll density gradient centrifugation. Two different methods were employed for determination of free Fe ions in erythrocytes, desferrioxamine (DFO) method and bleomycin method. DFO-chelatable Fe ions were detected in whole erythrocytes from 2 donors, and the DFO-chelatable free Fe ion levels in senescent erythrocytes were higher than those in young erythrocytes. Bleomycin-sensitive Fe ions, which was rather lower than DFO-chelatable Fe ions, were also detected in whole erythrocytes from 5 donors, and the free Fe ion levels in senescent erythrocytes were also higher than those in young erythrocytes. Free Fe ions may be derived from oxidative damage of hemoglobin, because treatment of whole erythrocytes or purified oxyhemoglobin with hydrogen peroxide gave increased free Fe ions. The results indicated that free Fe ions were released from erythrocytes during aging process in the circulation. Released free Fe ions would promote oxidative damages of the cells during aging process.

Bleomycin↗
PubMed2002

Domestic drinking water--an effective way to prevent anemia among low socioeconomic families in Brazil.

Iron deficiency and iron-deficiency anemia are common in the developing world. We evaluated the feasibility of iron fortification of domestic drinking water to prevent and control iron deficiency and iron-deficiency anemia. Twenty-one families representing 88 persons, including children, were selected to participate in this study. Twelve families added an iron solution plus ascorbic acid to their domestic drinking water over a four months period and nine families added a placebo. Blood samples were collected, before and after the four months, for hemoglobin and serum ferritin measurements. Iron-fortified drinking water increased hemoglobin (children 10.9 +/- 1.1 g/dl to 11.7 +/- 1.1 g/dl p < .01, adults 12.9 +/- 1.7 g/dl to 13.7 +/- 1.7 g/dl p < .01) and ferritin (children 27.6 +/- 21.6 ng/dl to 33.8 +/- 22.1 ng/dl, adults 74.8 +/- 41.3 ng/dl to 106.2 +/- 93.9 ng/dl p < .05). No significant changes in hemoglobin and ferritin were found in the placebo group after 4 months. Preparation, distribution, and consumption of the solutions were successful. Iron fortification of household drinking water can be a simple and effective alternative to deal with iron deficiency and iron-deficiency anemia in less developed areas.

Adult↗
PubMed2004

Metabolism and hemoglobin adduct formation of acrylamide in humans.

Acrylamide (AM), used in the manufacture of polyacrylamide and grouting agents, is produced during the cooking of foods. Workplace exposure to AM can occur through the dermal and inhalation routes. The objectives of this study were to evaluate the metabolism of AM in humans following oral administration, to compare hemoglobin adduct formation on oral and dermal administration, and to measure hormone levels. The health of the people exposed under controlled conditions was continually monitored. Prior to conducting exposures in humans, a low-dose study was conducted in rats administered 3 mg/kg (1,2,3-13C3) AM by gavage. The study protocol was reviewed and approved by Institute Review Boards both at RTI, which performed the sample analysis, and the clinical research center conducting the study. (1,2,3-13C3) AM was administered in an aqueous solution orally (single dose of 0.5, 1.0, or 3.0 mg/kg) or dermally (three daily doses of 3.0 mg/kg) to sterile male volunteers. Urine samples (3 mg/kg oral dose) were analyzed for AM metabolites using 13C NMR spectroscopy. Approximately 86% of the urinary metabolites were derived from GSH conjugation and excreted as N-acetyl-S-(3-amino-3-oxopropyl)cysteine and its S-oxide. Glycidamide, glyceramide, and low levels of N-acetyl-S-(3-amino-2-hydroxy-3-oxopropyl)cysteine were detected in urine. On oral administration, a linear dose response was observed for N-(2-carbamoylethyl)valine (AAVal) and N-(2-carbamoyl-2-hydroxyethyl)valine (GAVal) in hemoglobin. Dermal administration resulted in lower levels of AAVal and GAVal. This study indicated that humans metabolize AM via glycidamide to a lesser extent than rodents, and dermal uptake was approximately 6.6% of that observed with oral uptake.

Acrylamide↗