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PubMed1985

Alpha zero-thalassemia due to recombination between the alpha 1-globin gene and an AluI repeat.

A form of alpha zero-thalassemia found in subjects of Mediterranean origin has been analyzed by gene mapping and DNA sequencing. Homozygotes have the hemoglobin Bart's hydrops fetalis syndrome, while compound heterozygotes for this defect and alpha+-thalassemia have hemoglobin H disease. It results from a deletion that removes 20.5 kilobases of DNA from within the alpha-globin gene cluster. Sequence data from the regions adjacent to the breakpoint indicate that the recombination event that caused this deletion occurred between the alpha 1-gene and an unusual AluI sequence located between the embryonic zeta genes.

Chromosome Deletion↗
PubMed2004

Direct electron transfer and bioelectrocatalysis of hemoglobin at a carbon nanotube electrode.

A stable suspension of carbon nanotube (CNT) can be obtained by dispersing the CNT in the solution of the surfactant cetyltrimethylammonium bromide. CNT has promotion effects on the direct electron transfer of hemoglobin (Hb), which was immobilized onto the surface of CNT. The direct electron transfer rate of Hb was greatly enhanced after it was immobilized onto the surface of CNT. Cyclic voltammetric results showed a pair of well-defined redox peaks, which corresponded to the direct electron transfer of Hb, with the formal potential (E(0('))) at about -0.343V (vs. saturated calomel electrode) in the phosphate buffer solution (pH 6.8). The electrochemical parameters such as apparent heterogeneous electron transfer rate constant (k(s)) and the value of formal potential (E(0('))) were estimated. The dependence of E(0(')) on solution pH indicated that the direct electron transfer reaction of Hb is a one-electron transfer coupled with a one-proton transfer reaction process. The experimental results also demonstrated that the immobilized Hb retained its bioelectrocatalytic activity to the reduction of H(2)O(2). The electrocatalytic current was proportional to the concentration of H(2)O(2) at least up to 20mM.

Cetrimonium↗
PubMed1994

In vivo tissue dosimetry as a basis for cross-species extrapolation in cancer risk assessment of propylene oxide.

The potential for causing carcinogenic and mutagenic effects has been the main concern when assessing the risks associated with low-level exposures of humans to the industrially important epoxide, propylene oxide (PrO). For regulatory purposes, surface-based extrapolation has been used to determine the human equivalent dose from cancer data obtained in rodents. In this context the tissue dose will more adequately reflect inter- and intraspecies differences with respect to pharmacokinetic parameters than is the case for conventional representations of exposure. The formation of adducts in nucleophilic molecular targets by directly acting electrophilic agents, like epoxides, is thought to be closely linked to the process of cancer initiation. To investigate whether tissue dose is correlated to surface area of the exposed organism, the in vivo adduct levels in hemoglobin and DNA have been determined in mice, rats, and dogs after exposure to PrO by injection as well as by inhalation. The results obtained indicate that the dose in blood is virtually the same in the three investigated animal species, whereas surface-area based extrapolation predicts a difference by a factor of about seven between the mouse and the dog. Although the data base is more limited, this conclusion is also supported by measurements of DNA alkylation is selected tissues. The variations actually observed are not related to the surface area of the animal. No significant differences could be found between administration of PrO by injection or by inhalation. For this reason, the surface-based extrapolation model for estimation of the human equivalent dose is not appropriate, and the carcinogenic potency factors for PrO as previously derived by the U.S. EPA should probably be revised downward by a factor of 10 to 13.

Alkylating Agents↗
PubMed2001

Relative effectiveness of iron bis-glycinate chelate (Ferrochel) and ferrous sulfate in the control of iron deficiency in pregnant women.

The relative effectiveness of daily supplementation of iron deficiency during pregnancy using 15 mg/day of iron from iron-bis-glycinate chelate (71 pregnant women), or 40 mg iron from ferrous sulfate (74 pregnant women) was evaluated by measuring hemoglobin, transferrin saturation and serum ferritin, at the beginning of the study (< 20 weeks of pregnancy) and at 20-30 weeks and 30-40 weeks thereafter. Ingestion for 13 weeks or more was considered adequate. Seventy three percent of the Ferrochel consuming group and 35% of the ferrous sulfate consuming group were considered to have taken the treatment adequately. The decrease in levels of all the measured parameters was significantly less pronounced in the group that consumed Ferrochel in spite of the lower treatment dose. Iron depletion was found in 30.8% of the women treated with Ferrochel and in 54.5% of the women than consumed ferrous sulfate. Of the factors responsible for non compliance taste was reported in 29.8% of the ferrous sulfate consumers and none in the groups that consumed Ferrochel. It is concluded that daily supplementation with Ferrochel was significantly more effective, in spite of the lower dose, than supplementation with ferrous sulfate.

Anemia, Iron-Deficiency↗
PubMed1996

Subcutaneous epoetin alfa as an adjunct to autologous blood donation before elective coronary artery bypass graft surgery.

Autologous blood (AB) donation can minimize exposure to allogeneic blood in patients scheduled for coronary artery bypass graft (CABG) surgery. During AB donation in this group of patients, minimization of the accompanying decrease in hemoglobin (Hb) levels is important to reduce the risk of provoking silent myocardial ischemia and/or arrhythmias. Recombinant human erythropoietin (rHuEPO) has been used to facilitate AB donation and minimize the accompanying decrease in Hb levels in patients scheduled for cardiac surgery. In 24 patients scheduled for CABG surgery, once-weekly subcutaneous (s.c.) administration of rHuEPO (epoetin alfa 400 IU/kg) plus oral iron supplementation for 4 weeks prior to surgery caused marked stimulation of erythropoiesis and significantly increased collection of autologous red blood cells (RBCs) compared with oral iron alone. Furthermore, epoetin alfa minimized the decrease in Hb levels associated with AB donation and significantly attenuated allogeneic blood requirements by facilitating the collection of 4 AB units prior to surgery. During AB donation, no changes in the incidence or severity of ischemic attacks or ST-segment changes were observed using electrocardiographic monitoring. Epoetin alfa was well tolerated. Once-weekly s.c. administration of epoetin alfa for 4 weeks therefore represents a practical means of facilitating AB donation by patients scheduled for CABG surgery.

Anemia↗
PubMed2003

Induction of micronuclei in mouse and rat by glycidamide, genotoxic metabolite of acrylamide.

Male CBA mice and male Sprague-Dawley rats were treated by i.p. injection of glycidamide (GA), the presumed genotoxic metabolite of acrylamide (AA). GA was obtained through a new way of synthesis. As an endpoint of chromosome damage, micronucleus (MN) induction in erythrocytes was measured. Hemoglobin (Hb) adducts were used as a measure of in vivo dose of GA. GA induced linear dose-dependent increases in adduct levels in both species. Rats exhibit, compared with mice, 30% higher Hb adduct levels per unit of administered amount of GA. The incremental MN frequencies per administered dose of GA in mice showed a linear-quadratic dose-dependent curve. In the rat no positive dose-response relationship was obtained, probably due to toxic effects to the bone marrow. The main result of this study is the finding that after treatment with synthetic GA the MN frequency per unit of the in vivo dose of GA in the mouse is very similar to that obtained in a previous study, where animals were treated with AA and GA as a metabolite. This equality in potency of GA, whether its in vivo dose is established by injection of synthetic GA or through metabolism of AA, supports the view that GA is the predominant genotoxic factor in AA exposure.

Acrylamide↗
PubMed1992

A role for complement receptor-like molecules in iron acquisition by Candida albicans.

Candida albicans, an opportunistic fungal pathogen of humans, is dependent upon iron for growth. Consequently, human serum inhibits C. albicans growth due to the presence of high affinity iron-binding proteins that sequester serum iron, making it unavailable for use by the organism. We report that in the inhibitory environment of human serum, the growth of C. albicans can be restored by the addition of exogenous hemoglobin or heme, but not by protoporphyrin IX, the heme precursor that does not contain iron. We further report that C. albicans can utilize cell surface proteins that are homologues of the mammalian complement receptors (CR) to rosette complement-coated red blood cells (RBC) and obtain RBC-derived iron for growth. The ability of Candida to acquire RBC-derived iron under these conditions is dependent upon Candida-RBC rosetting mediated by CR-like molecules. Unopsonized RBC do not support Candida growth in serum, and restoration of Candida growth in serum by complement-opsonized RBC is inhibited by monoclonal antibodies to the human CR type 3 (CR3). In addition, activation of the human alternative pathway of complement by Candida leads to "bystander" deposition of C3 fragments on the surface of autologous, unopsonized RBC, generating the ligands necessary for Candida-RBC rosetting. These results suggest that C. albicans has evolved a unique strategy for acquiring iron from the host, which exploits the host complement system, and which may contribute to the pathogenic potential of the organism.

Animals↗
PubMed1976

Biological availability of iron supplements for rats, chicks and humans.

Fourteen experiments were concluded on the effect of protein and carbohydrate sources in the assay diets on the relative biological values (RBV) of food grade sodium iron pyrophosphate (NaFePP) and ferric orthophosphate (FePO4) vs. ferrous sulfate (FeSO4) for rats and chicks, using the response in blood hemoglobin to graded levels of supplemental iron as the assay criterion. Two trials were made with volunteers to estimate the RBV of NaFePP and FePO4 for humans, based on the increase in plasma iron 2 hours after ingestion of 100 mg of iron of a test dose following an overnight fast. The RBV of iron from NaFePP and FePO4 for rats were consistently lower when the basal diet contained nonfat dried milk (9 to 16 and 28, respectively, vs. FeSO4=100) than when casein was used (25 to 28 and 49, respectively). The addition of 22% beta-lactose, replacing sucrose in a diet containing casein fed to rats, significantly reduced the RBV of iron from NaFePP from 25 to 15; the addition of 22% alpha-lactose or 40% glucose in place of sucrose had no effect on the RBV of this iron source. The RBV of iron from NaFePP and FePO4 for chicks were 4 to 6 and 4, respectively, with the source of dietary protein having no effect. Very low RBV of iron from NaFePP and FePO4 (4.3 and 5.9, respectively, vs. FeSO4=100) were also obtained with human subjects.

Animals↗
PubMed2006

Hemoglobins dioxygenate nitric oxide with high fidelity.

Distantly related members of the hemoglobin (Hb) superfamily including red blood cell Hb, muscle myoglobin (Mb) and the microbial flavohemoglobin (flavoHb) dioxygenate nitric oxide (.NO). The reaction serves important roles in .NO metabolism and detoxification throughout the aerobic biosphere. Analysis of the stoichiometric product nitrate shows greater than 99% double O-atom incorporation from Hb(18)O(2), Mb(18)O(2) and flavoHb(18)O(2) demonstrating a conserved high fidelity .NO dioxygenation mechanism. Whereas, reactions of .NO with the structurally unrelated Turbo cornutus MbO(2) or free superoxide radical (-O.(2)) yield sub-stoichiometric nitrate showing low fidelity O-atom incorporation. These and other results support a .NO dioxygenation mechanism involving (1) rapid reaction of .NO with a Fe(III-)O.(2) intermediate to form Fe(III-)OONO and (2) rapid isomerization of the Fe(III-)OONO intermediate to form nitrate. A sub-microsecond isomerization event is hypothesized in which the O-O bond homolyzes to form a protein caged [Fe(IV)O .NO(2)] intermediate and ferryl oxygen attacks .NO(2) to form nitrate. Hb functions as a .NO dioxygenase by controlling O(2) binding and electrochemistry, guiding .NO diffusion and reaction, and shielding highly reactive intermediates from solvent water and biomolecules.

Animals↗
PubMed2005

Invertebrate hemoglobins and nitric oxide: how heme pocket structure controls reactivity.

Hemoglobins (Hbs), generally defined as 5 or 6 coordinate heme proteins whose primary function is oxygen transport, are now recognized to occur in virtually all phyla of living organisms. Historically, study of their function focused on oxygen as a reversibly bound ligand of the ferrous form of the protein. Other diatomic ligands like carbon monoxide and nitric oxide were considered "non-physiological" but useful probes of structure-function relationships in Hbs. This investigatory landscape changed dramatically in the 1980s when nitric oxide was discovered to activate a heme protein, cyclic guanylate cyclase. Later, its activation was likened to Perutz' description of Hb's allosteric properties being triggered by a ligand-dependent "out-of-plane/into-plane" movement of the heme iron. In 1996, a functional role for nitric oxide in human and mammalian Hbs was demonstrated and since that time, the interest in NO as a physiologically relevant Hb ligand has greatly increased. Concomitantly, non-oxygen binding properties of Hbs have challenged the view that Hbs arose for their oxygen storage and transport properties. In this focused review we discuss some invertebrate Hbs' functionally significant reactions with nitric oxide and how strategic positioning of a few residues in the heme pocket plays an large role in the interplay of diatomic ligands to ferrous and ferric heme iron in these proteins.

Allosteric Site↗
PubMed2005

Assessments of the chemistry and vasodilatory activity of nitrite with hemoglobin under physiologically relevant conditions.

Hypoxic vasodilation involves detection of the oxygen content of blood by a sensor, which rapidly transduces this signal into vasodilatory bioactivity. Current perspectives on the molecular mechanism of this function hold that hemoglobin (Hb) operates as both oxygen sensor and a condition-responsive NO reactor that regulates the dispensing of bioactivity through release of the NO group from the beta-cys93 S-nitroso derivative of Hb, SNO-Hb. A common path to the formation of SNO-Hb involves oxidative transfer of the NO-group from heme to thiol. We have previously reported that the reaction of nitrite with deoxy-Hb, which furnishes heme-Fe(II)NO, represents one attractive route for the formation of SNO-Hb. Recent literature, however, posits that the nitrite-reductase reaction of Hb might produce physiological vasodilatory effects through NO that evades trapping on heme-Fe(II) and may be stored before release as Fe(III)NO. In this article, we briefly review current perspectives in NO biology on the nitrite-reductase reaction of Hb. We report in vitro spectroscopic (UV/Vis, EPR) studies that are difficult to reconcile with suggestions that this reaction either generates a heme-Fe(III)NO reservoir or significantly liberates NO. We further show in bioassay experiments that combinations of nitrite and deoxy-Hb--under conditions that suppress SNO-Hb formation--exhibit no direct vasodilatory activity. These results help underscore the differences between physiological, RBC-regulated, hypoxic vasodilation versus pharmacological effects of exogenous nitrite.

Biosensing Techniques↗
PubMed2006

Use of hemoglobin vesicles during cardiopulmonary bypass priming prevents neurocognitive decline in rats.

BACKGROUND: Homologous blood use is considered to be the gold standard for cardiopulmonary bypass (CPB) priming in infants despite exposure of the patient to potential cellular and humoral antigens. However, the use of hemoglobin vesicles (HbVs), artificial oxygen carriers that encapsulate a concentrated hemoglobin solution within phospholipid bilayer membranes, for CPB priming may prevent neurocognitive decline in infants. The goal of this study was to determine whether HbV use offsets hemodilution caused by patient/priming volume-mismatched CPB and thereby prevents the development of postoperative neurocognitive deficits. METHODS AND RESULTS: CPB was established in 28 male Sprague-Dawley rats (age, 14 to 16 weeks; weight, 450 grams) after cannulation of the tail artery and right atrium. The animals were randomly assigned to 1 of 3 groups: sham surgery (n=9), HbV (-) prime (n=10), or HbV (+) prime (n=9). CPB was conducted for 90 minutes at 200 mL/kg per minute. The hematocrit during CPB was 10.0+/-1.2% in the HbV (+) prime group and 9.9+/-1.3% in the HbV (-) prime group (P=not significant). Learning and memory function were evaluated using 2 different maze tests (Maze-1 and Maze-2, in which the arrival times to the target were measured on the first, third, fifth, and seventh postoperative days). Learning and memory function were significantly better in the HbV (+) prime group than in the HbV (-) prime group (Maze-1, P=0.012; Maze-2, P=0.042); there was no difference between the HbV (+) prime and the sham surgery group. CONCLUSIONS: The use of HbV for CPB priming may serve as a substitute for homologous blood to prevent the unacceptable hemodilution and contribute to maintenance of intact neurocognitive function.

Animals↗
PubMed2006

Pentacoordinate and hexacoordinate ferric hemes in acid medium: EPR, UV-Vis and CD studies of the giant extracellular hemoglobin of Glossoscolex paulistus.

The equilibrium complexity involving different axially coordinated hemes is peculiar to hemoglobins. The pH dependence of the spontaneous exchange of ligands in the extracellular hemoglobin from Glossoscolex paulistus was studied using UV-Vis, EPR, and CD spectroscopies. This protein has a complex oligomeric assembly with molecular weight of 3.1 MDa that presents an important cooperative effect. A complex coexistence of different species was observed in almost all pH values, except pH 7.0, where just aquomet species is present. Four new species were formed and coexist with the aquomethemoglobin upon acidification: (i) a "pure" low-spin hemichrome (Type II), also called hemichrome B, with an usual spin state (d(xy))(2)(d(xz),d(yz))(3); (ii) a strong g(max) hemichrome (Type I), also showing an usual spin state (d(xy))(2)(d(xz),d(yz))(3); (iii) a hemichrome with unusual spin state (d(xz),d(yz))(4)(d(xy))(1) (Type III); (iv) and a high-spin pentacoordinate species. CD measurements suggest that the mechanism of species formation could be related with an initial process of acid denaturation. However, it is worth mentioning that based on EPR the aquomet species remains even at acidic pH, indicating that the transitions are not complete. The "pure" low-spin hemichrome presents a parallel orientation of the imidazole ring planes but the strong g(max) hemichrome is a HALS (highly anisotropic low-spin) species indicating a reciprocally perpendicular orientation of the imidazole ring planes. The hemichromes and pentacoordinate formation mechanisms are discussed in detail.

Acids↗
PubMed2005

Nitric oxide scavenging by Mycobacterium leprae GlbO involves the formation of the ferric heme-bound peroxynitrite intermediate.

Ferrous oxygenated (Fe(II)O2) hemoglobins (Hb's) and myoglobins (Mb's) have been shown to react very rapidly with NO, yielding NO3(-) and the ferric heme-protein derivative (Fe(III)), by means of the ferric heme-bound peroxynitrite intermediate (Fe(III)OONO), according to the minimum reaction scheme: Fe(II)O2 + NO (k(on))--> Fe(III)OONO (h)--> Fe(III) + NO3(-). For most Hb's and Mb's, the first step (indicated by k(on)) is rate limiting, the overall reaction following a bimolecular behavior. By contrast, the rate of isomerization and dissociation of Fe(III)OONO (indicated by h) is rate limiting in NO scavenging by Fe(II)O2 murine neuroglobin, thus the overall reaction follows a monomolecular behavior. Here, we report the characterization of the NO scavenging reaction by Fe(II)O2 truncated Hb GlbO from Mycobacterium leprae. Values of k(on) (=2.1x10(6) M(-1) s(-1)) and h (=3.4 s(-1)) for NO scavenging by Fe(II)O2 M. leprae GlbO have been determined at pH 7.3 and 20.0 degrees C, the rate of Fe(III)OONO decay (h) is rate limiting. The Fe(III)OONO intermediate has been characterized by optical absorption spectroscopy in the Soret region. These results have been analyzed in parallel with those of monomeric and tetrameric globins as well as of flavoHb and discussed with regard to the three-dimensional structure of mycobacterial truncated Hbs and their proposed role in protection from nitrosative stress.

Bacterial Proteins↗
PubMed2001

Beta 93 modified hemoglobin: kinetic and conformational consequences.

The reactive sulfhydryl on Cys beta93 in human adult hemoglobin (HbA) has been the focus of much attention. It has purported functional roles such as a transporter of nitric oxide and a detoxifier of super oxide. In addition, it has a proposed role in the allosteric mechanism. The present study addresses the functional and conformational consequences of modifying the beta93 sulfhydryl using either maleimide or disulfide-based reactions. The geminate and bimolecular recombination of CO derivatives of several different beta93-modified Hbs in both solution and sol-gel matrixes provide a window into functional modifications associated with both the R and T states of these proteins. Nanosecond time-resolved visible resonance Raman spectroscopy is used to probe conformational consequences associated with the proximal heme environment. The results show functional and conformational consequences that depend on the specific chemistry used to modify beta93. Maleimide-based modification show the most significant alterations of R-state properties including a consistent pattern of a reduced geminate yield and a loss of the favorable heme-proximal histidine interaction normally seen for liganded R-state HbA. A mechanism based on a displacement of the side chain of Tyr beta145 is explored as a basis for this effect as well as other situations where there is loss of the quaternary enhancement effect. The quaternary enhancement effect refers to the enhancement of ligand binding properties of the alphabeta dimers when they are associated into the R-state tetramer.

Carboxyhemoglobin↗
PubMed1998

Synthesized allosteric effectors of the hemoglobin molecule: a possible mechanism for improved erythrocyte oxygen release capability in hemoglobinopathy H disease.

Patients with the nondeletion genotype of hemoglobinopathy H (HbH or beta4) disease have higher proportions of HbH and more severe tissue hypoxia than patients with the deletion genotype. Because these patients' red blood cells (RBCs) contain mainly two Hb species, HbH and HbA, the high proportion of HbA can be exploited by lowering its oxygen affinity; this would probably increase oxygen delivery to the RBCs and improve the patients' clinical phenotype. Allosteric effectors that induce a low-affinity Hb may be useful in this regard. We investigated the effect of a bezafibrate derivative, RSR-4, on the oxygen affinity of RBCs and purified hemolysates containing HbA and HbH. This allosteric effector crosses RBC membranes and binds reversibly to the alpha-chains of deoxy-Hb, decreasing hemoglobin oxygen affinity. The blood used was obtained from a patient with HbH disease (alphaTSaudi homozygote) whose HbH level was 33.5% as measured by high-performance liquid chromatography. Oxygen binding studies were performed in RBCs and purified hemolysates. RBCs incubated in the presence of 500 microM RSR-4 (2-[[[(3,5-dichloroanilino)-carbonyl]methyl]phenoxy]-2-methylpropi onic acid) in standard conditions (pH 7.4, 0.14 M NaCl, 37 degrees C) displayed an increase in their P50 value from 14.5 to 35.2 mm Hg. Oxygen binding studies in purified stripped hemolysates (pH 7.2, 0.1 M NaCl, 25 degrees C) showed that addition of both 500 microM RSR-4 and 1 mM of 2,3 diphosphoglycerate (DPG) led to an 11-fold decrease in oxygen affinity, whereas the addition of the natural effector DPG or RSR-4 alone produced a 2.7- and 5.7-fold decrease, respectively. In both cases, the oxygen equilibrium curves (OECs) were biphasic due to the presence of the noncooperative, high-oxygen-affinity HbH (beta4) component. After addition of RSR-4, the lower part of the OEC (corresponding to HbH) was not shifted compared with the upper part (corresponding to HbA). These results were confirmed by kinetic studies of CO recombination. Both experiments demonstrated that RSR-4 does not affect beta4 Hb. Our findings provide an experimental model for lowering the oxygen affinity of HbA in HbH-containing cells and suggest that the oxygen delivery capability of the latter would be thereby improved.

Allosteric Regulation↗
PubMed1996

[Effectiveness and tolerability of oral liquid ferrous gluconate in iron-deficiency anemia in pregnancy and in the immediate post-partum period: comparison with other liquid or solid formulations containing bivalent or trivalent iron].

UNLABELLED: From the early months of pregnancy and even more so later, women suffer a deficiency of iron along with a decline in their red blood cell count. It is also now clear that women who take iron supplements during pregnancy do not suffer the same post-natal reduction in hemoglobin and ferritin as those who don't make it. A study was therefore conducted on 40 women aged 20-35, with iron-deficiency anaemia during or immediately after pregnancy all of whom presented Hb < 10 gr/dl, Ht < 33% and serum iron < 60 micrograms/dl. All women with pregnancy-related pathological conditions, pre-existing on concomitant disease (Type I diabetes, heart diseases etc.) were excluded from the study. The women whose blood chemical parameters were largely homogeneous at the start of the study were divided into four treatment groups of 10 patients each and were treated as follows: Group A with oral liquid ferrous gluconate (75 mg per diem in 2 vials a day); Group B with solid ferrous gluconate (80 mg per diem in a single effervescent tablet); Group C with solid ferrous sulphate (105 mg per diem in a single tablet); and Group D with ferric protein succinylate (80 mg per diem in 2 vials a day). All were given iron treatment for 30 days. Treatment efficacy was analysed by comparing basal and final parameters using the T-test for paired dependent samples. The tolerance of the 4 treatment protocols was assessed by the analysis of any side effects such as nausea, vomiting, epigastric pain, diarrhoea, constipation or other disorders reported by patients during treatment. RESULTS: Analysis of the therapeutic efficacy parameters (red blood cells, hemoglobin, hematocrit and serum iron) showed significant improvements but no statistically significant differences between the groups. However, the Group A patients treated with oral doses of liquid ferrous gluconate received a significantly lower cumulative dose of iron elements than the other groups: in detail 150 mg (p < 0.05) less than Groups B and D; 900 mg (< 0.001) less than Group C. By the end of treatment the Group A patients revealed significant increases versus basal values in red blood cells (p < 0.001) 1,051,000 per mm3 or 33%, in Hb (p < 0.001) 2.83 gr/dl or 32%, in Ht (p < 0.001) 8.32% or 32%, in serum iron (p < 0.05) 19.5 micrograms/dl or 61%. The same group also showed an increase in Ferritin amounting to 7.8 micrograms/dl or 24% of the basal value. As to safety, only Group A patients reported no side effects and produced no drop-outs. Gastrointestinal and other aspecific side effects caused 1 drop-out each in Groups B and C and 2 drop-outs in Group D. CONCLUSION: Numerous preparations containing bivalent or trivalent iron are available for the treatment of iron-deficiency anaemia during or immediately after pregnancy. It has been shown that preparations containing ferrous salts (+2) are more easily absorbed than those containing ferric salts (+3) since the former can be immediately absorbed by the duodenal mucosa. The study reported here reveals that oral ferrous gluconate in liquid form is more effective and above all better tolerated than other solid or liquid formulations containing elementary iron.

Administration, Oral↗