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Iron-storage deficiency and iron supplementation in pregnancy.

Haematological parameters were determined in 146 pregnant patients seen before 20 weeks' gestation. Eighteen per cent had both reduced serum ferritin and raised serum transferrin values without significant anaemia, suggesting covert iron-storage deficiency. One group then received 120 mg elemental iron daily and the other no iron supplementation. Repeat haematological assessment 20 weeks later indicated that in 48% of patients a significant decrease in haemoglobin concentration occurred if no iron was given. Supplementary iron prevented this decrease from occurring in patients with iron stores, but was insufficient to restore depleted stores or to prevent depletion of iron stores in 34% of patients with adequate stores. It is suggested that patients with depleted iron stores require therapeutic doses of iron, whereas those with adequate stores require little or no iron supplementation.

Adolescent↗

Mössbauer effect: studies of the electronic structures of the heme.

On the basis of experimental Mössbauer evidence, the electronic structures of heme iron are discussed for Mb and Hb. In the deoxygenated state, it is concluded from the electric field gradient tensor and the temperature dependence of the quadrupole splitting that the ferrous iron is not in the tetragonal ligand field with the symmetry axis perpendicular to the heme. The experimental results are well explained solely by rhombic perturbation. The electronic ground state is a component of the 5E term, and the principal axis of the anisotrophy is parallel to the heme plane. In the oxygenated state, there is no decisive conclusion on the bonding structure of the O2 molecule to the heme. Still, the two models of Pauling and Griffith are consistent with experimental results. Considering a relaxation between two possible conformational states, the peculiar temperature dependence of the quadrupole splitting is resolved in Fe-O2 model compounds.

Chemical Phenomena↗

A comparative trial of a controlled-release iron tablet preparation ('Ferrocontin' Continus) and ferrous fumarate tablets.

A single-blind, crossover comparative study was carried out in 40 patients with iron deficiency anaemia to assess the clinical efficacy and tolerance of once daily treatment with a controlled-release preparation of ferrous glycine sulphate ('Ferrocontin' Continus) and ferrous fumarate. Patients were allocated at random to receive 1 tablet (equivalent to 100 mg elemental iron) daily of one or other preparation for 4 weeks and were then crossed over to the alternative preparation for a further 4 weeks. The results showed that the significant increases in haemoglobin, packed cell volume and mean corpuscular volume were similar with both preparations. Seventeen patients reported gastro-intestinal side-effects on one or both preparations and the incidence was slightly less in patients whilst receiving the ferrous glycine sulphate preparation. In 3 patients, side-effects were sufficiently severe whilst taking ferrous fumarate to warrant interruption of treatment in 2 and withdrawal from the study in the other.

Adult↗

Effects of low-dose iron supplementation in women with low serum ferritin concentration.

We studied effects of dose and treatment duration during low-dose iron supplementation in premenopausal, non-pregnant women, with initial serum ferritin and haemoglobin concentrations < 20 micrograms x l-1 and > or = 120 g x l-1, respectively. The study was randomized, double-blind and placebo-controlled. Three groups completed a 6-month study: placebo (n = 27), FE-9 (9 mg iron x day-1, n = 18) and FE-27 group (27 mg iron x day-1, n = 19). The supplement consisted of 11% heme and 89% inorganic iron. In FE-27, serum ferritin increased from (mean, 95% confidence interval) 11.8 (9.7; 14.4) to 25.3 (18.6; 34.4) micrograms x l-1 in 1 month, and remained stable after that (ANOVA: group effect, P = 0.0003). In both FE-9 and FE-27, blood haemoglobin levels increased from 136 (132; 140) to 142 (139; 145) g x l-1 in 1 month, remaining constant after that (group effect, P = 0.001). Hence, the 27 mg daily dose of organic/inorganic iron corrected both mild anaemia and storage iron depletion, whereas the 9 mg dose did not affect iron stores. Elongation of treatment duration above 1 month brought about only minor changes.

Adult↗

Potential of epoetin alfa in patients in autologous blood donation programs for orthopedic surgery.

The ability of epoetin alfa to increase hematopoiesis in a dose-dependent manner when administered by the intravenous (i.v.) or subcutaneous (s.c.) route has been demonstrated in pharmacokinetic studies in healthy volunteers. Epoetin alfa may therefore be a useful adjunct to autologous blood (AB) donation. By facilitating AB donation, the use of allogeneic blood could be reduced. In patients scheduled to undergo orthopedic surgery, i.v. administration of epoetin alfa 600 IU/kg twice weekly for 3 weeks prior to surgery (in conjunction with oral iron supplementation) significantly increased the number of AB units and total red blood cell (RBC) volume donated and increased the number of patients able to donate > or = 4 AB units. However, there was no difference between epoetin alfa and placebo groups with respect to allogeneic blood exposure.

Anemia↗

Blood substitutes for transfusion.

Faced with an increased demand for blood products and a stable donor pool, different companies have developed products for oxygen carrying from hemoglobin, to fluorocarbon based compounds (the latter based on Teflon like products). There are several difficulties in showing efficacy of these compounds, and the reasons are discussed. In addition, various strategies for production of oxygen-carrying blood substitutes (OCBS) are noted as well as other applications for these compounds.

Blood Substitutes↗

Automated quantification of TSH in serum by a chemiluminescent enzyme immunometric assay: analytical validation.

Thyroid stimulating hormone (thyrotropin; TSH) in serum was assayed with the Immulite-TSH, a fully automated solid-phase third-generation immunoassay analyzer that has a chemiluminescent detection system. The intraassay CV ranged from 3.6% to 6.2% for TSH mean concentrations from 0.025 to 32.12 mIU/L and the interassay CV ranged from 7.9% to 10% for TSH mean concentrations between 0.023 and 31.93 mIU/L. The analytical and functional detection limits of the assay were 0.001 and 0.0068 respectively. No interference was observed by any of the compounds: bilirubin, triglycerides, and hemoglobin. To compare the accuracy of Immulite-TSH with that of a conventional immuno-radiometric assay (Orion Diagnostica Irma-TSH), we examined 153 patient samples with TSH concentrations ranging approximately 0.2 to 100 mIU/L. At TSH concentration approximately 0.15 the precision was greater for Immulite-TSH than for Irma TSH (3.8% vs 11.87%) intraassay CV and (8.6% vs 35.4%) interassay CV. We concluded that Immulite-TSH is a rapid and precise third-generation assay, totally automated and the results can be provided to the clinician within 1 to 2 h of receipt of the patient's sample.

Humans↗

Clinical biochemistry, haematology and body weight in piglets.

Reference ranges for clinical biochemical parameters commonly investigated in pigs were determined in one- (day 1), 21- and 35-day old piglets. The mean and standard deviation were also estimated for body weight, and haematological and clinical biochemical parameters at these ages. The piglets were divided into 2 investigation groups according to whether they had a haemoglobin concentration < or = 80 g/l ("anaemic group") or > 80 g/l ("normal group") on days 14, 21 and 28. The "anaemic group" was compared to the "normal group" on days 21 and 35. Many of the clinical biochemical parameters varied according to age. Some of the enzymes had high average values and wide reference ranges in piglets, especially on day 1, compared to the reference ranges for sows given in the literature. The reference ranges for some of the metabolic parameters were broader on day 1 than later in the preweaning period. The reference ranges for albumin, total iron-binding capacity and serum iron were, however, lower and more narrow on day 1. On days 21 and 35, relatively high values for phosphorus must be considered "normal" compared to the figures given in the literature for adult pigs. The other minerals seemed to be quite unaffected of age, but some were affected by anaemia. The anaemic piglets had lower average serum iron but higher total iron-binding capacity than the "normal" piglets on days 21 and 35. However, variation between piglets gave wide reference ranges, indicating that these parameters will only have limited usefulness in detecting iron deficiency anaemia in piglets. The electrolytes seemed also to be affected by the existence of anaemia. The body weight and leukocyte counts were significantly lower in the "anaemic group" than the "normal group" on day 35, while the greatest differences in clinical biochemical parameters between the groups were found on day 21, when the piglets in the "anaemic group" were most severely anaemic. Although these piglets suffered from severe iron-deficiency anaemia, only a few clinical biochemical parameters were affected, and the differences between groups were mostly small.

Age Factors↗

A simple and rapid evaluation of methemoglobin toxicity of 8-aminoquinolines and related compounds.

Methemoglobin, a toxic ferric form of hemoglobin, is continuously formed in normal erythrocytes, but during abnormal situations in situ, the level is enhanced. 8-Amino-quinolines and related compounds are causative agents for methemoglobin formation. Employing oxyhemoglobin, methemoglobin toxicity was about six times higher with primaquine compared to CDRI Compound 80/53 at 10(-9) M concentration. Methemoglobin reductase activity was also completely inhibited by primaquine, whereas 24% inhibition was noted in the case of 80/53 at the same concentrations. Mastomys, a rodent animal model, was found to be equally good for comparative evaluation of methemoglobin toxicity. Further, with the use of primaquine transdermal tape on the Mastomys model, a rise in methemoglobin occurred with increase in time. In conclusion, the study presents simple, economical, less time-consuming methods for the evaluation of methemoglobin toxicity, in vitro and in vivo, without employing the conventional Beagle dog model.

Administration, Cutaneous↗

Resonance Raman detection of bound dioxygen in cytochrome P-450cam.

We have used resonance Raman spectroscopy and isotopic labeling techniques to unambiguously assign the dioxygen stretching frequency (vo-o) in the substrate-bound oxygenated complex of cytochrome P-450cam. The frequency found for Vo-o in the P-450cam system (1140 cm-1) is in remarkable agreement with recent studies of thiolate heme model compounds. The general features of the oxy-P-450cam Raman spectra are tabulated and comparisons are made with the oxy complexes of hemoglobin, myoglobin, and various model compounds. Most of the results are qualitatively explained by consideration of electron donation into the pi g (O2)/d pi (M) orbitals of the oxygenated complex (M = Fe or Co). It is also noted that the effect of the "extra" electron in the nitrogen base Co(II) oxy complexes, in some ways, parallels the effect of the lone pair electrons of thiolate in the oxy-P-450cam complex. This is evidenced by the enhanced resonance Raman activity of vo-o in both the Co(II) and P-450 systems as well as by the similarity of the vo-o frequencies.

Cytochrome P-450 Enzyme System↗

Physiological and x-ray studies of potential antisickling agents.

Several aromatic compounds have been found to inhibit the gelling of sickle cell hemoglobin. We have tried to correlate the antigelling activity of such compounds with the stereo-chemistry of their binding sites in the hemoglobin molecule. This approach led to the discovery that two known antilipoproteinemia drugs, clofibrate and gemfibrozil, have antigelling activity. X-ray analysis showed that three pairs of molecules of clofibric acid, the active metabolite of clofibrate, bound to the walls of the internal cavity of deoxyhemoglobin A; only one pair bound to a quite different site, between helices A, E, and H of the alpha chains of carbon monoxide hemoglobin A. Unlike other antigelling agents, clofibric acid and related compounds decrease rather than increase the oxygen affinity of hemoglobin.

Antisickling Agents↗

Monitoring exposure to 4,4'-methylenedianiline by the gas chromatography-mass spectrometry determination of adducts to hemoglobin.

The determination of the covalently bound reaction products of 4,4'-methylenedianiline (MDA) to hemoglobin was investigated as a possible method for biological dosimetry in humans. The extent of binding to rat hemoglobin of MDA was determined by dosing animals with the 14C-ring-labeled compound. Two adducts were released from the hemoglobin on hydrolysis under mildly basic conditions which were identified as MDA and N-acetyl-MDA and accounted for between 36 and 45% of the total radioactivity bound to the protein. A quantitative assay procedure was subsequently developed for measuring both of the base released adducts in rat hemoglobin. The method utilized solvent extraction followed by derivatization with pentafluoropropionic anhydride and subsequent separation and quantitation by capillary gas chromatography with selective ion monitoring mass spectrometry using deuterium-labeled analogues of MDA and N-acetyl-MDA as internal standards. A dose-response relationship was established in orally dosed rats between production of each of the hemoglobin released adducts and dose of MDA (1-12 mg/kg). The possible use of such adduct determinations as dosimeters for industrial workers exposed to MDA is discussed.

Aniline Compounds↗