Form Of Ferritin Research Articles

Eclectica, June 2010

Vascular calcification in its intimal (atherosclerotic) and medial (Monckeberg calcinosis) forms is much more common in patients with chronic kidney disease (CKD), occurs at a younger age, and correlates with the high rates of cardiovascular and all-cause mortality in this population. Elevated levels of inorganic phosphorous gain access to the vascular smooth muscle cells (VSMC) of the arteries via a sodium-dependent phosphate cotransporter, thereby triggering increased expression of alkaline phosphatase and a bone specific transcription factor, core binding factor alpha-1 (Cbfa-1) which induces osteoblastic transformation of VSMC which in turn begin to lay down hydroxyapatite, a form of calcium phosphate, in the arterial wall. These events are also associated with upregulation of osteocalcin, an important non collagenous bone matrix protein which regulates mineralization. Investigators have been examining various mechanisms that may retard this process of vascular calcification, which brings us to a consideration of heme, a ubiquitous ironcontaining molecule crucial for aerobic life; it induces the synthesis of heme oxygenase (HO-1), a rate limiting enzyme of heme catabolism which cleaves the porphyrin ring to form biliverdin and carbon monoxide, thus releasing free redox iron; the biliverdin is later reduced to bilirubin. Heme also induces the formation of the storage protein ferritin, a 450 kD shell that stores up to 4,500 iron atoms in a non toxic form, and has a heavy (H) and a light (L) chain; the latter chain being important not only for incorporating iron but also in diminishing oxidative tissue damage from ferrous iron. All of which brings us to the interesting experiments conducted by Zarjou et al. They raised human aortic smooth muscle cells (VSMC) in a high phosphorus culture medium and noted that the cells began to lay down calcium. Ferritin heavy chain and to a much lesser extent biliverdin, inhibited osteoblastic differentiation of VSMC and calcification; the iron chelator desferroxamine blocked this effect of ferritin, and a mutant form of ferritin lacking the ferroxidase activity could not reproduce the anticalcification effects of normal ferritin. Likewise ceruloplasmin, a molecule quite different from ferritin but also possessing ferroxidase activity, also inhibited calcification. Furthermore, the phosphorous-induced osteoblastic differentiation of VSMC, measured by the upregulation of Cbfa-1, alkaline phosphatase and osteocalcin, was also inhibited by ferritin/ferroxidase activity. The authors conclude that the HO-1/ferritin system blocks the phosphorous mediated osteoblastic transformation of VSMC and subsequent calcification, and hope that their findings offer a promise of clinical application. J Am Soc Nephrol20:1254

The magnetic-laser therapy in the system treatment of anemia in pregnant women infected with Helicobacter pylori

The article is presented with the results of comparing assessment of clinical efficiency of the magnetic-laser therapy in doublefrequency ranges (150 ang 1 500 Hz) combined with iron therapy (sorbifer 100 mg once a day) in treatment of benign anemia of pregnancy, running above with the chronic gastritis, associated with contamination of gastrointestinal tract by Helicobacter pylori. The results of treatment show that the clinical effect is optimal for noninvasive magnetic-laser impact on blood with 150 Hz frequency. This method allows to raise hemoglobin while maintaining the iron depot in the form of ferritin together with cutting off the infectious process on the gastrointestinal tract mucous.

Iron and Parenteral Nutrition

There is ample evidence that iron is an essential trace element, but assessment of iron status and decisions on the amounts needed and the means of delivery in patients on parenteral nutrition (PN) have been unclear. Although iron requirements may diminish during acute illness, the frequent concurrence of blood loss and iron deficiency argue strongly for maintenance of levels of delivery in line with basal requirements. Maintenance of iron delivery has not been thought likely to present risk, but new data are questioning this. The needs of menstruating, pregnant, and lactating women are greater than those of adult men. The evidence favors an intravenous dose of around 1 mg of elemental iron per day in adult men and postmenopausal women. Doses of 1.5 mg/d [DOSAGE ERROR CORRECTED] in menstruating women and 2.0 mg/d [DOSAGE ERROR CORRECTED] for those in the later stages of pregnancy or lactating can be supported. A calibrated response is required in the growing child. Continued monitoring of iron status is recommended. Iron is an essential component for most PN regimens. The quantity of iron to be included should take account of predicted requirements.

Cystic fibrosis: ironing out the problem of infection?

the study by moreau-marquis et al. (3) in this issue of AJP-Lung advances our understanding of lung disease in cystic fibrosis (CF). Their findings are important because they may largely explain the peculiar propensity to early Pseudomonas aeruginosa infection that characterizes this most common of lethal genetic diseases. Moreau-Marquis et al. (3) demonstrate that immortalized human CF airway epithelial cells cocultured with P. aeruginosa promote the formation of antibiotic-resistant biofilms. Their series of experiments demonstrate that this is due to abnormal accumulation and loss of iron by CF epithelial cells and that biofilm formation can be prevented by either iron chelation therapy or by increasing normal cell membrane cystic fibrosis transmembrane regulator (CFTR) expression using the novel compound Corr4a. The observations of Moreau-Marquis et al. (3) confirm what has been clinically suspected in CF with respect to iron promotion of infection with P. aeruginosa. Previous studies have demonstrated that the airways of CF patients contain increased amounts of total iron and the iron-binding protein ferritin as well as a relationship between airway iron content and quantitative P. aeruginosa load assessed by colony-forming units per milliliter of sputum (5). This study also found an increase in iron in sputum in CF patients who had not previously been infected with P. aeruginosa, suggesting that elevated airway iron content may predate P. aeruginosa acquisition. Further evidence to support a problem with iron trafficking comes from the CF G551D mouse model. The teeth of these mice exhibit abnormal iron transport in pigment ameloblasts compared with wild-type mice, resulting in unusually white dentition (7). The study by Moreau-Marquis et al. (3) lends biological rationale to these earlier observations and brings two key questions into focus. First, what is the underlying link between abnormal or absent CFTR and cell iron homeostasis? Second, how does this impact on the CF host and P. aeruginosa interaction?

Structural Characterization of Iron in Human Spleen

ABSTRACTIron is essential element for fundamental cell functions, catalyst for chemical reaction. Iron can be found in human body mainly in the form of ferritin - 5Fe2O3.9H2O.57Fe Mössbauer spectrometry, X4ray powder diffraction, (XRD), X4ray fluorescence (XRF), scanning and transmission electron microscopy (TEM) were carried out for investigation of iron oxide particles in human spleens with diagnosis of hemosiderosis, hereditary spherocytosis, and reference sample.Room temperature Mössbauer spectra of all investigated samples exhibit doublet4like features identified as Fe(III) predominantly in ferrihydrite and haem environments within the tissue. Low temperature Mössbauer effect measurements at 77 K revealed, however, no changes in the magnetic ordering of the investigated samples. A contribution of ferromagnetically split sextets is clearly seen for all investigated samples measured at 5K. Their occurrence indicates that part of the sample is magnetically ordered, i.e. below the blocking temperature of a superparamagnetic behaviour. The ratio of relative contents of doublet to sextet components suggests differences in the size of ferritin cores in the investigated samples. The hemosiderosis sample exhibits the largest ferritin core which, in turn, stores the highest amount of Fe and thus triggers this disease.Additional structural characterization is obtained from powder XRD and XRF measurements. XRF results show presence of different chemical elements such as iron, sulphur, phosporus, chlorine, zinc, chromium, and bromine. TEM investigation reveals iron accumulation in macrophages of the human spleen. The size of the particles is around 5 μm.The amount of chemical elements and pH in surrounding environments can influence iron oxidation status and may cause transformation of biogenic to abiogenic (toxic) character of ferritin.

Effects of dietary factors on iron uptake from ferritin by Caco-2 cells

Biofortification of staple foods with iron (Fe) in the form of ferritin (Ft) is now possible, both by conventional plant breeding methods and transgenic approaches. Ft–Fe from plants and animals is absorbed well (25–30%) by human subjects, but little is known about dietary factors affecting its absorption. We used human intestinal Caco-2 cells and compared Fe absorption from animal Ft and FeSO 4 to determine the effects of inhibitors and enhancers, such as phytic acid, ascorbic acid, tannic acid, calcium and heme. When postconfluent cells were coincubated with 59Fe-labeled (1 μM) FeSO 4 and dietary factors, at different molar ratios of dietary factor to Fe (phytic acid:Fe, 10:1; ascorbic acid:Fe, 50:1; tannic acid:Fe, 50:1; calcium:Fe, 10:1 and hemin:Fe, 10:1), all inhibited uptake from FeSO 4, except ascorbate, confirming earlier studies. In contrast, these dietary factors had little or no effect on Fe uptake from undigested Ft or Ft digested in vitro at pH 4, except tannins. However, results after in vitro digestion of Ft at pH 2 were similar to those obtained for FeSO 4. These results suggest that Fe uptake occurs from both undigested as well as digested Ft but, possibly, via different mechanisms. The Fe–Ft stability shown here could minimize Fe-induced oxidation of Fe-supplemented food products.

Human Polymorphonuclear Leukocytes Inhibit Aspergillus fumigatus Conidial Growth by Lactoferrin-Mediated Iron Depletion

Aspergillus fumigatus, a common mold, rarely infects humans, except during prolonged neutropenia or in cases of chronic granulomatous disease (CGD), a primary immunodeficiency caused by mutations in the NADPH oxidase that normally produces fungicidal reactive oxygen species. Filamentous hyphae of Aspergillus are killed by normal, but not CGD polymorphonuclear leukocytes (PMN); however, the few studies on PMN-mediated host defenses against infectious conidia (spores) of this organism have yielded conflicting results, some showing that PMN do not inhibit conidial growth, with others showing that they do, most likely using reactive oxygen species. Given that CGD patients are exposed daily to hundreds of viable A. fumigatus conidia, yet considerable numbers of them survive years without infection, we reasoned that PMN use ROS-independent mechanisms to combat Aspergillus. We show that human PMN from both normal controls and CGD patients are equipotent at arresting the growth of Aspergillus conidia in vitro, indicating the presence of a reactive oxygen species-independent factor(s). Cell-free supernatants of degranulated normal and CGD neutrophils both suppressed fungal growth and were found to be rich in lactoferrin, an abundant PMN secondary granule protein. Purified iron-poor lactoferrin at concentrations occurring in PMN supernatants (and reported in human mucosal secretions in vivo) decreased fungal growth, whereas saturation of lactoferrin or PMN supernatants with iron, or testing in the presence of excess iron in the form of ferritin, completely abolished activity against conidia. These results demonstrate that PMN lactoferrin sequestration of iron is important for host defense against Aspergillus.

Iron Chelation and Vascular Function

In 1981, Sullivan suggested that a state of iron depletion (ie, reduced iron stores without anemia) was potentially protective against coronary heart disease (CHD).1 This original “iron hypothesis” was an attempt to explain the known sex difference in cardiovascular (CV) risk and the subsequent loss of the protective effect of female gender with menopause. This initial hypothesis was based in part on the observation that men exhibited an age-dependent increase in the accumulation of iron that was not seen in women until after menopause. This, coupled with the observation that hysterectomy without oophorectomy was associated with an increased CHD risk, supported the concept that a diminution in iron stores was protective against CHD. Basic and clinical data have recently begun to provide plausible explanations for a link between iron and atherosclerosis.2,3 See page 2282 The toxic effect of free iron has been linked to oxidative stress through the Fenton reaction, where Fe2+ oxidizes H2O2 leading to its autooxidation and the generation of hydroxyl radicals4 which in turn initiate lipid peroxidation. In addition, biological forms of iron such as heme have the potential to catalyze other oxidative reactions. For example, heme can initiate the oxidation of isolated LDL in vitro4 and, in contrast to free transition metals, LDL in diluted serum.5 Iron is also essential for the synthesis of enzymes that can play a central role in vascular function and atherosclerosis (eg, eNOS, 5-lipoxygenase, and myeloperoxidase). The amount of free ferrous (Fe2+) iron is normally maintained at a very low level in …

Denatured H-ferritin subunit is a major constituent of haemosiderin in the liver of patients with iron overload.

Iron is stored in hepatocytes in the form of ferritin and haemosiderin. There is a marked increase in iron rich haemosiderin in iron overloaded livers, and ferric iron in amounts exceeding the ferritin and haemosiderin binding capacity may promote free radical generation, causing cellular damage. The aim of this study was to characterise hepatic haemosiderin using four antibodies specific for either native or denatured H/L-ferritin subunits. Ferritin and haemosiderin were prepared from the livers of three patients with post-transfusional iron overload. The assembled ferritin molecules were analysed by non-denaturing polyacrylamide gel electrophoresis (PAGE)-immunoblotting. Ferritin subunits in the haemosiderin fraction were assessed by denaturing sodium dodecyl sulphate (SDS)-PAGE-immunoblotting. Distribution of native and denatured ferritin subunits in hepatocytes was examined by immunogold electron microscopy. Non-denaturing PAGE-immunoblot analyses showed that the assembled liver ferritins were recognised by the antibodies for native ferritins and not by those for the denatured subunits. Both SDS-PAGE-immunoblot and immunogold electron microscopic analyses disclosed that haemosiderin of iron overloaded liver reacted predominantly to the monoclonal antibody for the denatured H-ferritin subunit, to a lesser degree to that for denatured L-ferritin, and very weakly, if any, with antibodies for native H-ferritin or L-ferritin. These results suggest that in iron overloaded liver, haemosiderin consists predominantly of denatured H-ferritin subunits.

Chemical speciation of iron deposits in thalassemic heart tissue

Heart tissue from β-thalassemia/hemoglobin E patients was taken at autopsy. The patients had received no blood transfusions or iron chelation therapy. Ferritin and hemosiderin were isolated from the tissue and studied using 57Fe Mössbauer spectroscopy, transmission electron microscopy and electron diffraction. The ferritin was shown to contain mineral cores with a mean particle size of 7.37 (s.d. 0.84) nm. Electron diffraction and Mössbauer spectroscopy indicated that the cores had structures based on that of the mineral ferrihydrite and were superparamagnetic with a mean blocking temperature of 34 K on the Mössbauer measurement time scale. The hemosiderin particles ranged in size from 1 to 10 nm and were indicated to have a very poor crystalline structure. Mössbauer spectroscopic measurement indicated that the majority of the iron in the hemosiderin was paramagnetic/superparamagnetic at 4.2 K. Mössbauer spectroscopy of the heart tissue indicted that approximately 40% of the tissue iron is in the form of hemosiderin, 35% in the form of ferritin, 3% in the form of heme iron, and approximately 20% in the form of an unidentified form of iron that yields a spectral singlet with centre shift of 0.32 mm s−1 at 15 K with respect to α-iron at room temperature.

Iron Release From Human Monocytes After Erythrophagocytosis In Vitro: An Investigation in Normal Subjects and Hereditary Hemochromatosis Patients

This study investigated the release of erythrocyte-derived iron from purified human monocytes obtained from healthy volunteers and hereditary hemochromatosis (HH) patients. After erythrophagocytosis of59Fe-labeled erythrocytes, a complete transfer of iron from hemoglobin (Hb) to ferritin was observed within 24 hours in both control and HH monocytes. The iron was released from the monocytes in the form of ferritin, Hb, and as nonprotein bound low molecular weight iron (LMW-Fe). During the initial rapid phase (<1.5 hours), iron release mostly consisted of Hb and LMW-Fe, while in the later phase (>1.5 hours), it was composed of ferritin and LMW-Fe. The kinetics of iron release were identical for HH monocytes. A high percentage of the total amount of iron was released as Hb both by viable normal and HH monocytes, suggesting that iron release as Hb is a physiologic process, which may occur whenever the erythrocyte-processing capacity of macrophages is exceeded. Most remarkably, HH monocytes released twice as much iron in a LMW form as control cells. Iron released in the form of LMW-Fe readily binds to plasma transferrin and may contribute to the high transferrin saturation and the occurrence of circulating nontransferrin-bound iron observed in HH patients.

Iron Release From Human Monocytes After Erythrophagocytosis In Vitro: An Investigation in Normal Subjects and Hereditary Hemochromatosis Patients

This study investigated the release of erythrocyte-derived iron from purified human monocytes obtained from healthy volunteers and hereditary hemochromatosis (HH) patients. After erythrophagocytosis of59Fe-labeled erythrocytes, a complete transfer of iron from hemoglobin (Hb) to ferritin was observed within 24 hours in both control and HH monocytes. The iron was released from the monocytes in the form of ferritin, Hb, and as nonprotein bound low molecular weight iron (LMW-Fe). During the initial rapid phase (<1.5 hours), iron release mostly consisted of Hb and LMW-Fe, while in the later phase (>1.5 hours), it was composed of ferritin and LMW-Fe. The kinetics of iron release were identical for HH monocytes. A high percentage of the total amount of iron was released as Hb both by viable normal and HH monocytes, suggesting that iron release as Hb is a physiologic process, which may occur whenever the erythrocyte-processing capacity of macrophages is exceeded. Most remarkably, HH monocytes released twice as much iron in a LMW form as control cells. Iron released in the form of LMW-Fe readily binds to plasma transferrin and may contribute to the high transferrin saturation and the occurrence of circulating nontransferrin-bound iron observed in HH patients.

IN VIVO ACCUMULATION OF IRON ON CROCIDOLITE IS ASSOCIATED WITH DECREMENTS IN OXIDANT GENERATION BY THE FIBER

In vivo exposures to fibrous silicates are characterized by the formation of asbestos bodies. These structures consist of the original fiber with a coating of inexact composition, but it will include iron and protein. We tested the hypothesis that this iron, accumulated on asbestos bodies, participates in electron transport and oxidant generation. Thirty-day-old, male guinea pigs were intratracheally instilled with 1.0 mg crocidolite. Six months later, the animals were anesthetized, euthanized, and the fibers were isolated from the lungs. Energy-dispersive x-ray analysis and x-ray photoelectron spectroscopy confirmed an accumulation of metal onto the fiber after in vivo exposure. Stains for iron demonstrated a heterogeneous distribution of the metal on the silicate, while the uptake of a commercially available polyclonal antibody to ferritin localized to beaded enlargements along the coated 3+ fibers. Chelatable [Fe ] associated with the fiber increased after in vivo exposure. However, oxidant generation by asbestos bodies was decreased relative to uncoated fibers despite the elevation in the concentration of metal associated with the crocidolite. We conclude that iron is accumulated onto fibers in the lungs of guinea pigs. Some portion of this accumulation of iron is in the form of ferritin, and this metal is not chemically reactive in oxidant production. Asbestos bodies may represent a successful attempt by the host to sequester the metal adsorbed to the surface of a fiber and diminish the oxidative challenge introduced by a fibrous silicate. Subsequently, the generation of free radicals by the fibrous silicate is diminished.

Anaemia in juvenile chronic arthritis.

Anaemia is a common manifestation of juvenile rheumatoid arthritis (JCA). We have evaluated 26 JCA patients with anaemia and compared their laboratory parameters to those without anaemia. In the patients with anaemia, activation criteria such as erythrocyte sedimentation rate (ESR) and CRP were significantly higher than in those without anaemia. Anaemia was present in all systemic JCA patients and was present in 42% and 78% of the oligoarticular and polyarticular types, respectively. Serum iron levels and transferrin saturations were low in all, whereas serum iron-binding capacities of the patients were normal. Mean ferritin level was 249pg/l (range 8.46-1000pg/l). There was a significant correlation between ferritin levels and CRP and ESR (r = 0.48 and r = 0.55 respectively) (both p < 0.05). Epo levels were normal. Twelve (60%) of the bone marrow aspiration specimens stained positive for iron whereas 40% stained negative; there were also changes suggestive of myelodysplasia. Sideroblasts were also decreased in number. Thus, in these patients iron is not sufficiently transferred to the erythroid series and/or cannot be used by erythroblasts, accompanied by a possible absolute iron deficiency. Thus we suggest that the iron in JCA tends to be stored in the form of ferritin, not in an accessible form and impaired metabolism along with other factors are effective in the anaemia of JCA.

Magnetic resonance imaging of brain iron in health and disease

Brain iron is a major contributor to magnetic resonance imaging (MRI) contrast in normal gray matter, and its role in the pathogenesis of different neurological disorders has also become apparent. Non-heme brain iron is present in the brain mainly in the form of ferritin. The unique magnetic properties of ferritin determine different signal changes on both T1- and T2-weighted images, and the T2 relaxation rates have a linear dependence on applied field strength. This finding is typical for ferric oxyhydroxide cores. The resulting T2-shortening also depends on echo-spacing used in the imaging sequence as well as on the water diffusion coefficient and the size of the ferritin cluster. Quantitation of non-heme brain iron by MRI aids in the diagnosis and monitoring of different neurological diseases.

Pattern of Iron Storage in the Rat Heart Following Iron Overloading with Trimethylhexanoyl-Ferrocene

Female Wistar rats with slight iron deficiency anemia were kept on a diet containing 0.5% trimethylhexanoyl (TMH)-ferrocene for up to 79 weeks. In the state of iron deficiency, the heart was free of light-microscopically detectable iron. After 7 weeks of the TMH-ferrocene diet, the first iron-positive granules appeared in perivascular macrophages. Further oral administration caused a progression of iron deposition in these cells, visible in the form of a granular staining but also as a diffuse iron staining of the cytoplasm. Accordingly, at the electron-microscopical level, the iron was stored partly as free ferritin molecules in the cytosol, and partly in lysosomes in the form of ferritin and/or hemosiderin. After 11 weeks, further iron-positive cells with relatively small dark-blue granules were found in the vicinity of capillaries, which could be identified as fibrocytes by means of electron microscopy. In addition, slight iron deposition occurred in the endothelial cells of the cardiac capillaries, likewise mainly in the form of small, uniform siderosomes. The myocytes showed no product of Perls' Prussian blue reaction during the whole period of investigation. From the 11th week onwards, discrete ferritin molecules were detected electron microscopically within lysosomes of these cells. Their amount increased slowly with progression of the TMH-ferrocene feeding period. Free ferritin molecules could be observed in the cytosol of fibrocytes, endothelial cells and myocytes in only very slight concentrations, whilst they were more plentiful in macrophages. In hereditary hemochromatosis and posttransfusional siderosis, the iron is found predominantly in myocytes and appears to cause cell damage, whilst this is not the case in experimental iron overload in rats.

Brain iron homeostasis

The anatomical and cellular distribution of non-haem iron, ferritin, transferrin, and the transferrin receptor have been studied in postmortem human brain and these studies, together with data on the uptake and transport of labeled iron, by the rat brain, have been used to elucidate the role of iron and other metal ions in certain neurological disorders. High levels of non-haem iron, mainly in the form of ferritin, are found in the extrapyramidal system, associated predominantly with glial cells. In contrast to non-haem iron, the density of transferrin receptors is highest in cortical and brainstem structures and appears to relate to the iron requirement of neurones for mitochondiral respiratory activity. Transferrin is synthesized within the brain by oligodendrocytes and the choroid plexus, and is present in neurones, consistent with receptor mediated uptake. The uptake of iron into the brain appears to be by a two-stage process involving initial deposition of iron in the brain capillary endothelium by serum transferrin, and subsequent transfer of iron to brain-derived transferrin and transport within the brain to sites with a high transferrin receptor density. A second, as yet unidentified mechanism, may be involved in the transfer of iron from neurones possessing transferrin receptors to sites of storage in glial cells in the extrapyramidal system. The distribution of iron and the transferrin receptor may be of relevance to iron-induced free radical formation and selective neuronal vulnerability in neurodegenerative disorders.

Immunocytochemical detection of ferritin in human bone marrow and peripheral blood cells using monoclonal antibodies specific for the H and L subunit

We have used the monoclonal antibodies 2A4 (specific for the H subunit of human ferritin) and LO3 (specific for the L subunit) for immunocytochemical detection of ferritin in bone marrow and peripheral blood cells from normal subjects and patients with various haematological disorders. Formalin-fixed slides were stained by the immunoalkaline phosphatase procedure (APAAP). In normal subjects, ferritin could be found only in bone marrow smears and appeared to be largely confined to erythroid precursors and reticuloendothelial cells. The more immature erythroid precursors contained higher concentrations of cellular ferritin. Although evaluation could be only semiquantitative, erythroblast ferritin appeared to be more reactive with the monoclonal 2A4 (15 +/- 7% positive erythroblasts) than with the monoclonal LO3 (6 +/- 5% positive erythroblasts), indicating that H-type ferritin was predominant, particularly in proerythroblasts and basophilic erythroblasts. By contrast, the ferritin present in reticuloendothelial cells appeared to be predominantly of L-type. Patients with iron deficiency showed low levels of positive erythroblast, whereas the reverse was true in patients with transfusional iron overload. Intense positivity for reticuloendothelial cell ferritin was found in patients with anaemia of chronic disease. In myelodysplastic syndromes and acute myeloid leukaemia (AML), ferritin positivity was generally very strong at any stage of erythroblast development, particularly with the monoclonal antibody 2A4. Perls-positive perinuclear granules of ring sideroblasts were not stained, confirming that mitochondrial iron deposition is not in the form of ferritin. In AML and myelodysplastic syndromes with excess of blasts, ferritin could be detected also in immature myeloid cells. These data indicate that: (a) in normal conditions ferritin is mainly expressed in red cell precursors and reticuloendothelial cells, and this is in keeping with the peculiar role of these cells in iron metabolism; (b) abnormal cell ferritin contents can be observed in both iron overload and malignancy.

Mössbauer study of cobalt and iron in the cyanobacterium (blue green alga)

Mossbauer emission and absorption studies have been performed on cobalt and iron in the cyanobacterium (blue-green alga). The Mossbauer spectrum of the cyanobacterium cultivated with57Co is decomposed into two doublets. The parameters of the major doublet are in good agreement with those of cyanocobalamin (vitamin B12) labeled with57Co. The other minor doublet has parameters close to those of Fe(II) coordinated with six nitrogen atoms. These suggest that cobalt is used for the biosynthesis of vitamin B12 or its analogs in the cyanobacterium. The spectra of the cyanobacterium grown with57Fe show that iron is in the high-spin trivalent state and possibly in the form of ferritin, iron storage protein.

Hepatic iron in dialysed patients given intravenous iron dextran.

Five percutaneous biopsy and 17 necropsy liver specimens were analysed histologically and chemically for iron content in 22 patients receiving dialysis for chronic renal failure, 13 of whom were given intravenous iron-dextran. Brissot scores for assessing histological hepatic iron deposition and chemically measured liver iron concentrations correlated closely. Both variables depended on total cumulative dose of iron, and to a lesser extent, on time since the last dose. Fibrosis (seen in five patients) was minimal and non-specific. Electron microscopic examination showed that there was no generalised damage and confirmed the presence of iron in the hepatocytes in the form of ferritin. High liver iron concentrations, in excess of 1000 micrograms/100 mg dry weight, were seen in two patients. Four others given comparable cumulated amounts (18-23 g iron) did not have such high concentrations. Plasma ferritin concentrations were high in eight patients, some with and some without fibrosis. The risk of temporarily high iron deposition in the liver causing damage seemed to be minimal when weighed against the benefit of increased haemoglobin in most of the patients. Intravenous iron treatment merits further evaluation, particularly with the advent of erythropoietin treatment, which requires continuously available iron.