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PubMed1980

The effect of riboflavin on the hematologic changes in iron supplementation of schoolchildren.

A supplementation trial was carried out in 101 children, 6-12 years of age, in 3 primary schools in a rural area. Their hemoglobin level and PCV (mean +/- SD) were 11.64 +/- 1.21 g/dl and 0.356 +/- 0.028 respectively, 74% of them were anemic and the hemoglobin level were correlated with the MCHC (P < .01) . Fifty-one per cent of them had hookworm infection and all those with hemoglobin levels below 10 g/dl had hookworm infection, but there was no difference in mean hemoglobin level between those with hookworm infection and those without. The children were divided into 3 groups: Group I comprising 39 children who received placebo tablest; Group II of 33, who received ferrous sulphate (60 mg elemental iron); Group III of 29, who received ferrous sulphate (60 mg elemental iron) with riboflavin (6mg). Each child received one tablet after lunch on schooldays and evaluation was carried out after receiving 80 to 90 tablets. The mean hemoglobin change of Group II was 0.60 g/dl larger than that of Group I (P < .005) with 52% of them responding to iron. The mean hemoglobin change of Group III was 0.38 g/dl larger than that of Group II (P < .005) with 86% of them responding to iron and riboflavin. Thus additional riboflavin is beneficial in iron supplementation.

Child↗
PubMed2001

Functional characterization of heme proteins encapsulated in wet nanoporous silica gels.

Myoglobin and hemoglobin were encapsulated in wet, nanoporous silica gels. A rigorous evaluation of the effect of the encapsulation on protein dynamics and function was carried out by measuring the kinetics of carbon monoxide rebinding after nanosecond laser flash-photolysis with transient absorption detection, and the oxygen affinity with absorption microspectrophotometry. The time course of carbon monoxide binding to myoglobin evidenced a strongly enhanced geminate recombination and a faster bimolecular rebinding with respect to solution, whereas T and R quaternary states of hemoglobin exhibited a geminate phase and a bimolecular binding rate very similar to those observed in solution. Oxygen affinity of T-state hemoglobin was found to be close to that observed for the binding of the first oxygen to T-state hemoglobin in solution. Results indicate that some conformational transitions are kinetically restricted, allowing to isolate distinct tertiary and quaternary states. This opens the way to their detailed functional characterization and application to biodevices.

Absorption↗
PubMed1977

Effect of ligands of ferric hemes on interaction between ferric and ferrous chains in partially oxidized hemoglobin A.

Normal values of Bohr effect of oxygenation of partially oxidized hemoglobin A with ferrihemes liganded either with H2O and OH or with CN have been found in the range of pH values from 6.8 to 7.6 in 45 micrometer (Fe)-hemoglobin containing 36--38% of ferrihemes. As the changes of oxygen affinity of Hb A induced by changes of pH are due to the modifications of R state, this quaternary conformation is thought to be unchanged in the studied of R state, this quaternary conformation is thought to be unchanged in the studied forms of partially oxidized hemoglobin. It is suggested that interactions between ferric and ferrous hemes leading to the increased affinity of ferrous hemes to oxygen occur in deoxygenated form of partially oxidized hemoglobin. In partially oxidized hemoglobin with ferric hemes liganded with H2O asymmetry of oxygen binding curves has been noted, which is not observed in forms with ferric hemes liganded with OH ot CN. This shows the effect of ligands of ferric hemes on interactions between chains containing ferric and ferrous hemes.

Ferric Compounds↗
PubMed2001

Effectiveness of treatment of iron-deficiency anemia in infants and young children with ferrous bis-glycinate chelate.

Forty infants, 6 to 36 mo old, with iron-deficiency anemia (hemoglobin < 11 g/dL) were matched and assigned to two groups. One group received FeS0(4) and the other received ferrous bis-glycinate chelate at a dose of 5 mg of Fe daily per kilogram of body weight for 28 d. Both groups had significant hemoglobin increases (P < 0.001), but only the group treated with ferrous bis-glycinate chelate had significant increases (P < 0.005) in plasma ferritin. Apparent iron bioavailabilities were calculated at 26.7% for FeS0(4) and 90.9% for ferrous bis-glycinate chelate. Regression analysis indicated that absorption of both sources of iron were similarly regulated by the body according to changes in hemoglobin. We concluded that ferrous bis-glycinate chelate is the iron of choice for the treatment of infants with iron-deficiency anemia because of its high bioavailability and good regulation.

Anemia, Iron-Deficiency↗
PubMed1998

Stabilization of the T-state of ferrous human adult and fetal hemoglobin by Ln(III) complexes: a thermodynamic study.

The effect of the lanthanide(III) complexes [Gd(1,4,7,10-tetraazacyclododecane-N,N',N", N"'-tetrakis(methylenephosphonate))]5- (Gd-DOTP) and La-DOTP on the oxygen binding and spectroscopic properties of human adult and fetal hemoglobin (HbA and HbF, respectively) has been investigated. The affinity of Gd-DOTP and La-DOTP for oxygenated HbA (HbAO2; KHbAO2 = 2.6 x 10(-3) M) is closely similar to that observed for Ln(III) complexes association to nitrosylated HbA (HbANO KHbANO = 1.8 x 10(-3) M) and to aquo-met HbA (met-HbA; Kmet-HbA = 1.9 x 10(-3) M), being lower than that determined for Gd-DOTP and La-DOTP binding to the deoxygenated form of the tetramer (HbAd; KHbAd = 3.0 x 10(-4) M). The affinity of Gd-DOTP for deoxygenated HbF (HbFd; KHbFd = 9.5 x 10(-4) M) and oxygenated HbF (HbFO2; KHbFO2 = 3.7 x 10(-3) M) is lower than that observed for Ln(III) complexes association to HbAd and HbAO2, respectively. Gd-DOTP and La-DOTP bind to HbA and HbF with a 1:1 stoichiometry per tetramer. Increasing Gd-DOTP and La-DOTP concentration, oxygen affinity for HbA decreases (i.e. P50 increases), this effect being minor for HbF. Upon binding of Ln(III) complexes to HbANO, the X-band EPR spectrum and the absorption spectrum in the Soret region display the characteristics which have been attributed to the T-state of the ligated tetramer. These results represent a clear cut evidence for the specific binding of Gd-DOTP and La-DOTP to the 2,3-D-glycerate bisphosphate (BPG) pocket (i.e. at the dyad axis, in between the beta-chains) of HbA and HbF. The effect of Ln(III) complexes on the ligand binding and spectroscopic properties of HbA and HbF is reminiscent that of BPG, the physiological modulator of human Hb action.

Adult↗
PubMed1984

Noncovalent inhibitors of sickle hemoglobin gelation: effects of tetrasubstituted ammonium salts.

The effects of various tetrasubstituted ammonium compounds on the solubility of deoxygenated sickle hemoglobin were evaluated. These conclusions were drawn from the slopes of the solubility profiles obtained: (1) for the homologous series of tetraalkylammonium chloride salts (R4NCl), antigelling potency increased with increasing chain length of the R group: Ch3 less than C2H5 less than C3H7 less than C4H9; (2) for halide salts of the tetrabutylammonium cation there was no difference in effectiveness among the anions examined (Br-, Cl-, F-), presumably because of the extremely potent salting-in effect of this cation; (3) substitution of a benzyl for an alkyl group in three tetraalkylammonium chloride salts, C6H5CH2(R)3NCl, where R = CH3, C2H5, or C4H9, potentiated the antigelling capacity by as much as eight-fold. Because they are substantially more water soluble than any other class of noncovalent inhibitors examined to date, further manipulation of the aryl substituent on these compounds may contribute to the design of an effective antisickling agent.

Amines↗
PubMed1965

LOCALIZATION OF ERYTHROCYTE MEMBRANE SULFHYDRYL GROUPS ESSENTIAL FOR GLUCOSE TRANSPORT.

The reactions of three organic mercurial compounds, chlormerodrin, parachloromercuribenzoate (PCMB), and parachloromercuribenzenesulfonate (PCMBS) with intact red blood cells, hemolyzed red cells, hemoglobin solutions, and hemoglobin-free ghosts have been characterized. Both PCMB and PCMBS react with only 2 to 3 sulfhydryl groups per mole of hemoglobin in solution, whereas chlormerodrin reacts with 6 to 7. In hemoglobin-free ghosts, however, all three reagents react with a similar number of sulfhydryl groups, approximately 4 x 10(-17) moles per cell, or about 25 per cent of the total stromal sulfhydryl groups, which react with inorganic mercuric chloride. In the intact cell the membrane imposes a diffusion barrier; chlormerodrin and PCMB penetrate slowly, whereas PCMBS does not. Kinetic studies of chlormerodrin binding to intact cells reveal that the majority of stromal sulfhydryl groups is located inside the diffusion barrier, with only 1 to 1.5 per cent (or 1 to 1,400,000 sites per cell) located outside of this barrier. Reaction of PCMBS with intact cells is limited to this small fraction on the outer membrane surface. All three reagents are capable of inhibiting glucose transport in the red cell. With chlormerodrin and PCMBS it was demonstrated that the inhibition results from interactions with the sulfhydryl groups located on the outer surface of the membrane.

Biological Transport↗
PubMed1994

Influence of the polymerization step alone on oxygen affinity and cooperativity during production of hyperpolymers from native hemoglobins with crosslinkers.

The aim of this study was to find out how the polymerization per se changes oxygen affinity (P50) and cooperativity (n50) of various soluble huge hyperpolymers prepared from native hemoglobins by crosslinking. Increase of cooperativity would be expected considering natural hemoglobin networks. Those hyperpolymers with molecular weights of some 10(6) g/mol are candidates for artificial oxygen-carrying blood additives rather than volume substitutes. Human and bovine hemoglobin reacted with several crosslinkers (2,5-diisothiocyanatobenzenesulfonate (DIBS); 4,4'-diisothiocyanatostilbene-2, 2'-disulfonate (DIDS); 1,3-butadiene diepoxide (BUDE); glutaraldehyde (GDA)) in concentrated (case 1) and diluted (case 2) hemoglobin solutions. With high concentration hyperpolymer and with low concentration only monomer products were obtained. P50 and n50 of the products were determined at pH = 7.4, PCO2 = 40 mmHg, temp. = 37 degrees C. The difference of properties in both cases are regarded as the influence of polymerization per se. Considering this difference we found with almost all combinations of hemoglobin and crosslinker an increase of O2 affinity, with DIBS and DIDS cooperativity was not changed and with BUDE and GDA it was decreased. As compared with native hemoglobin loss of cooperativity is considerable in any combination and condition, but comparing human and bovine hemoglobin the first seems to maintain better cooperativity. In contrast bovine hemoglobin as compared with human hemoglobin maintains better or even decreases its O2 affinity upon reaction with the crosslinkers forming both, monomer and hyperpolymer products, especially in the deoxy state. DIBS and DIDS react very similarly.(ABSTRACT TRUNCATED AT 250 WORDS)

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1995

Diffuse optics determination of hemoglobin derivatives in red blood cells and liposome encapsulated hemoglobin.

High resolution optical absorption spectra of hemoglobin derivatives in red blood cells and phosphatidylcholine liposomes were calculated from diffuse reflection and transmission spectra by means of the one-dimensional diffusion approximation. The numerical technique of singular value decomposition was used to calculate the composition of red cell and liposome mixtures.

Animals↗
PubMed1993

Oxygen transport capacity and hemodynamic effect of newly developed artificial blood "Neo Red Cells (NRC)".

The purpose of this study was to evaluate liposome-encapsulated hemoglobin, named Neo Red Cells (NRC), on hemodynamics and oxygen-transport capacity in a blood exchange experiment. The experiment was carried out in nine mongrel dogs. Depending on the percentage of blood exchange with NRC, the animals were divided into two groups; Group I (4 animals with an exchange rate less than 88%), and Group II (5 animals with an exchange rate over 88%). After blood exchange, total peripheral vascular resistance index (TPRI) decreased and cardiac index (CI) increased. These changes were more marked in Group II than in Group I, thus showing that NRC relieved the burden on the heart, probably due to the fact that the viscosity of NRC is 2 cp which is less than 1/3 that of whole blood. The oxygen binding capacity per 1g hemoglobin in NRC was 2-4 times as much as red blood cells. Thus, NRC was superior to natural red blood cells in terms of oxygen transport capacity and its effects on the circulatory system.

Animals↗
PubMed1990

Molecular pathology of hemoglobin M Saskatoon disease.

Absorption spectra of erythrocyte hemolysate from a normal subject, the Hemoglobin (Hb1) M Saskatoon patient and the Hb M Boston patients were investigated. Difference spectrum between the hemolysate from either freshly obtained or 37 degrees C-incubated blood of the Hb M Saskatoon patient and that of the normal blood suggested that about 50% of the abnormal chain were in the ferrous state in the patient's blood. In contrast, no abnormal chain containing the ferrous heme was detected in the hemolysate from the fresh blood of the Hb M Boston patient. Resonance Raman (RR) studies indicated that methemoglobin (metHb) M Saskatoon with a weak Fe-tyrosinate interaction contained the six-coordinate heme like normal metHb A whereas metHb M Boston had the five-coordinate heme. Studies on effects of pH on absorption and RR spectra of these three hemoglobins suggested that the coordinated tyrosinate in the abnormal chain of Hb M Saskatoon was dissociated at pH 5.0. This unique heme structure of Hb M Saskatoon may relate to the susceptibility for the reduction by erythrocyte methemoglobin reductases, which is responsible for mild cyanosis of Hb M Saskatoon disease.

Ferrous Compounds↗
PubMed2000

Effects of NADH and H(2)O(2) on chromate-induced human erythrocytes hemoglobin oxidation and peroxidation.

The effects of NADH and H(2)O(2) on chromate-induced human erythrocyte hemoglobin oxidation and peroxidation were studied. It was observed that NADH decreases the levels of chromate-induced human erythrocyte hemoglobin oxidation and peroxidation. H(2)O(2) decreases the levels of chromate-induced hemoglobin oxidation, but increases the levels of chromate-induced peroxidation. The ability of H(2)O(2) to decrease the levels of chromate-induced hemoglobin oxidation is higher than that observed for NADH. Furthermore, H(2)O(2) increases the inhibitory effect of NADH on chromate-induced hemoglobin oxidation, but decreases the NADH effect on chromate-induced peroxidation. The meaning of these results is discussed in terms of involvement of reactive chromium(V) species and reactive oxygen species in the mechanism by which chromate induces its effects in human erythrocytes.

Cell Culture Techniques↗
PubMed1999

[Direct genotyping of an hereditary persistence of fetal hemoglobin deletion and rapid prenatal diagnosis of the fetus at-risk for compound heterozygote of this defect with beta-thalassemia in a Chinese family].

OBJECTIVE: To investigate the relationship between genotype and phenotype of a deletional hereditary persistence of fetal hemoglobin(HPFH) found in a Chinese family and explore an approach to rapid prenatal diagnosis for compound heterozygote of HPFH defects with beta-thalassemia. METHODS: By using the PCR-based method with three primers bridging a HPFH breakpoint and reverse dot blot (RDB) for detecting beta-thalassemia mutations, a Chinese family who had a propositus of six years old with intermediate thalassemia and requested prenatal diagnosis for the second pregnancy were screened. RESULTS: The propositus carried the HPFH deletion determinant inherited from her mother, and a codons 14-15 (+G) frameshift mutation causing beta-thalassemia from her father. Of six members in this family screened for this type of HPFH deletion, four were positive. Prenatal diagnosis of the fetus showed the same results as that of the propositus. An advice of termination of pregnancy was given and the result of prenatal diagnosis was confirmed in the DNA samples obtained after abortion. CONCLUSIONS: This is the first time to have performed prenatal diagnosis of Chinese family at-risk for compound heterozygotes for beta-thalassemia and HPFH in mainland China. The PCR assay for directly detecting the HPFH deletion is rapid and inexpensive and can be used as a routine in HPFH carrier screening and prenatal diagnosis.

Adult↗
PubMed1992

Iron status in low-birth-weight infants, small and appropriate for gestational age. A follow-up study.

Iron nutrition was measured in 84 low-birth-weight infants. At birth, they were assigned to three groups: preterm infants appropriate for gestational age (n = 29); preterm infants small for gestational age (n = 17); and full-term infants small for gestational age (n = 38). A sub-sample of infants was supplemented with iron 3 mg/kg from two to four months of age. At birth, preterm appropriate-for-gestational-age infants had a lower hemoglobin concentration than full-term small-for-gestational-age infants (p < 0.01) and a higher serum ferritin than preterm small-for-gestational-age infants (p < 0.05). In the non-supplemented group, full-term small-for-gestational-age infants had significantly higher hemoglobin concentrations at four months of age. At this age, iron-supplemented preterm infants appropriate or small for gestational age had significantly higher hemoglobin levels than non-supplemented subjects, while iron supplementation did not have an effect on final hemoglobin concentration in full-term small-for-gestational-age infants. We conclude that preterm infants, irrespective of their adequacy for gestational age, show evidence of iron deficiency before four months of age. Full-term infants do not develop iron deficiency up to this age.

Anemia, Hypochromic↗
PubMed1992

A guide to primary care of iron-deficiency anemia.

Iron deficiency, the most common cause of anemia, is prevalent in 10 percent to 30 percent of the world's population. Inadequate intake of iron may be an important causative factor, particularly when the body requires more iron than usual (e.g., during infancy, early childhood, adolescence, pregnancy and periods of blood loss). The popular increase of fiber in diets may increase the incidence of iron-deficiency anemia because too much fiber in the diet renders available iron unabsorbable. Symptoms in children include skin or conjunctival pallor, excessive sleepiness, learning disabilities, diminished attention span, tiredness, irritability or inappropriate behavior, and pica. Adults may have shortness of breath, decrease in exercise tolerance, palpitations, tachycardia, angina, congestive heart failure, orthopnea and edema. Iron deficiency occurs in sequential states and is measured by many laboratory tests. The levels of hemoglobin and hematocrit are both decreased, while the red blood cell count may be normal initially, but will decrease as the iron-deficiency state continues. The steps of treatment include correction of the underlying disorder, administration of the amount of iron needed and observation of the response to treatment.

Adolescent↗
PubMed1978

Effects of dietary corn on hematological response of anemic rats to ferrous sulfate.

Anemic rats were fed diets containing adequate quantities of all required nutrients, except iron, which was supplied by ferrous sulfate and/or corn grain. Diets were supplemented with the inorganic salt and corn in such a pattern that regression of hematological response on increments of ferrous sulfate intake could be calculated for 0, 25%, 50% and 75% dietary corn. Corn was added to the diets at the expense of starch which served only as a source of energy. Slopes of the regression lines for response (hemoglobin iron gain or final hemoglobin concentration) to ferrous sulfate intake were not altered significantly by inclusion of up to 75% corn in the diets. Results indicate that corn does not contain an inhibitor of iron absorption. Poor iron absorption from diets or meals in which corn provides a significant portion of the total food supply is probably due to a nutritional inadequacy of the corn, possibly its amino acid imbalance.

Anemia, Hypochromic↗
PubMed1978

Hematopoietic studies in vitamin A deficiency.

Recent studies of experimental vitamin A deficiency in man led the authors to conclude that anemia may result from lack of vitamin A. A review of numerous nutrition surveys in underdeveloped countries enhanced the suspicion that deficiency of vitamin A does contribute to the prevalence of anemia. Preliminary studies of vitamin A-deficient rats confirmed previous observations that anemia may result from lack of this vitamin. The livers of these animals had very low concentrations of vitamin A but normal or increased concentrations of iron. The finding of anemia is in contrast with other reports that vitamin A deficiency may cause elevated values for hemoglobin and hematocrit. The authors suggest that loss of taste and smell as a result of deficiency may account for refusal of experimental animals to eat and drink enough to prevent inanitation and dehydration. The resulting hemoconcentration may mask the true hematological picture, which is one of anemia.

Adolescent↗