SEARCH · Search PubMed

Results for “Iron Overload”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 523 records · Page 29Linked to original sources

PubMed2001

Iron overload can induce mild copper deficiency.

Dietary copper in the U.S. often is lower than that proved insufficient for men and women under controlled conditions. Iron overload can have adverse effects on copper nutriture and can produce cardiac disease in people. The hypothesis that iron can interfere with copper utilization to produce adverse effects related to cardiovascular function was tested. Rats were fed a diet high in iron and marginal, but not deficient in copper for comparison with similar diets containing iron at the recommended amount. Copper and iron were measured by atomic absorption spectroscopy; cholesterol was measured by fluorescence, ceruloplasmin was measured by oxidase activity and hematology was done by an automated cell counter. When dietary copper was 2.0 mg/kg of diet, high iron decreased (p<0.008) cardiac and hepatic copper, plasma copper and ceruloplasmin, and increased (p<0.02) cardiac weight, hepatic iron and plasma cholesterol. When dietary copper was increased to 2.5 mg/kg, copper in heart and plasma decreased (p<0.04) and hepatic iron increased (p=0.001) with high iron but other effects disappeared. No harmful changes in hematology, such as hematocrit, mean corpuscular volume, etc. were found. High iron increased the dietary copper requirement of the animals. People with iron overload may benefit from copper supplementation, particularly if they habitually consume a diet low in copper.

Animals↗

PubMed2004

Hyperferritinaemia without iron overload: pathogenic and therapeutic implications.

It is not unusual to meet increased levels of ferritinaemia in patients apparently healthy. Among other causes of hyperferritinaemia, recently was described the Hereditary Hyperferritinemia Cataract Syndrome, a genetic condition characterized by increased serum ferritin values without iron overload and bilateral nuclear cataract, both of early onset. It has been demonstrated that single or double point mutations or deletions in the stem-loop structure of the iron regulatory element (I.R.E.) located in the 5 untranslated regions of the ferritin L-subunit gene (19q13.1) are responsible for the upregulation of ferritin. This overexpression only for the L-chain gives rise to typical piles in several tissues. When this altered ferritin accumulates in lens it causes bilateral nuclear cataracts, that is the peculiar sign of this syndrome. It is essential to differentiate true iron overload from Hereditary Hyperferritinaemia Cataract Syndrome (H.H.C.S.), because these patients rapidly develop iron deficient anaemia when venosectioned. Here we describe a case report about a 40 years old healthy female blood donor who presented isolated hyperferritinaemia without iron overload, in the absence of concomitant pathologies. Anamnestic, biochemical, instrumental and clinical investigations led us to diagnose H.H.C.S., a pathology first described in 1995. From 1995 to date about 40 cases concerning patients showing the characteristics of this syndrome from Europe, USA, and Australia were described. Biochemical, genetical and clinical investigations led finally to understand every matter of this pathology, providing conclusive and exhaustive explanations.

Animals↗

PubMed1993

Echocardiographic study in ex-thalassemic patients with iron overload, preliminary observations during phlebotomy therapy.

In patients with thalassemia major iron overload leads to symptoms of cardiac failure and it is the most frequent cause of death. A sub group of asymptomatic thalassemic patients (Th Pts) who underwent bone marrow transplantation (BMT) and who presented persistently high serum ferritin level and heavy haemosiderosis were subjected to cardiological study to evaluate possible iron-related cardiac disease. We report here preliminary results obtained from the Echocardiographic studies carried out at baseline and at eight months follow-up in a group of ex-thalassemic after transplant who underwent phlebotomy in the attempt to reduce the iron overload.

Adolescent↗

PubMed1994

Biliary excretion of plasma non-transferrin-bound iron in rats: pathogenetic importance in iron-overload disorders.

Plasma non-transferrin-bound iron (NTB-iron) is a potentially toxic form of iron, which is efficiently taken up by the normal, as well as the chronically iron-overloaded liver. In fact, NTB-iron may represent the major source of iron gaining access to hepatocytes in the iron-loaded state. We postulated that efficient biliary excretion of this form of iron could protect against iron-related hepatocellular injury. To characterize the biliary excretion of NTB-iron in intact normal and iron-loaded rats, the plasma disappearance and biliary excretion kinetics of plasma 55Fe-labeled NTB-iron were determined. In normal rats, prompt biliary excretion of plasma NTB-iron was evident, with peak radioactivity approximately 10 min after 55Fe injection (4.1% mean recovery at 3 h). In contrast, biliary iron excretion in iron-loaded rats was minimal (0.1%). In normal rats, a marked increase in biliary excretion of plasma NTB-iron was observed after intravenous desferrioxamine (mean recovery 20.9%) and the new oral iron chelator 1,2-dimethyl-3-hydroxypyrid-4-one administered intravenously (mean recovery 16.1%) or orally (11.4%). In iron-loaded rats, the cumulative recoveries of 55Fe in bile achieved by chelators were lower than in controls (7.6, 3.9, and 3.7%, respectively). Collectively, these findings demonstrate that 1) the normal liver rapidly excretes significant amounts of plasma NTB-iron in bile; 2) the iron-loaded liver exhibits a marked decrease in the capacity to excrete plasma NTB-iron into bile; and 3) chelating agents greatly enhance the biliary excretion of plasma NTB-iron, although the response in terms of cumulative recoveries is less pronounced in the iron-loaded state.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Non-invasive assessment of tissue iron overload in the liver by magnetic resonance imaging.

We investigated the clinical usefulness of a standard magnetic resonance imaging (MRI) system for non-invasive determination of the liver iron concentration in 38 patients with iron overload and 15 normal controls by measurement of the signal intensity ratio between liver and skeletal muscle (SIR). However, SIR was found dependent on the applied repetition time (TR) of the MRI system, which led us to investigate this relationship in autopsy material of liver and muscle tissue specimens with various iron content. Based on these results, adjustment of SIR measurements to a constant value of TR was achieved. By use of this technique we found a close correlation between MRI and chemically determined liver iron concentration (r2 = 0.98) as well as the serum ferritin concentration (r2 = 0.86). The reproducibility was sufficiently good for the use of MRI in the follow-up of iron reductive treatment. The use of iron store parameters in serum was found insufficient as indicators of endpoint for venesection therapy, if 20 mumol Fe/g dry weight was applied as the upper reference limit of the liver iron concentration. It is concluded that MRI based on SIR measurements offers a precise and reproducible non-invasive method for the determination and follow-up of iron overload within a wide range of liver iron concentrations. Our findings may increase the clinical use of MRI in haematological patients with iron overload.

Bloodletting↗

PubMed2005

1/T2 and magnetic susceptibility measurements in a gerbil cardiac iron overload model.

PURPOSE: To measure the transverse relaxation rate (1/T2) and magnetic susceptibility of the heart in conditions of iron overload by using magnetic resonance (MR) imaging and to correlate these with the tissue iron concentration in a gerbil model. MATERIALS AND METHODS: With prior approval by the institutional animal care and use committee, iron overload was induced with one to 15 weekly subcutaneous injections of iron dextran. Nine gerbils had one to five injections, 10 had six to 10, and eight had 13-15. T2 of the whole heart was measured ex vivo (n=27), and the magnetic susceptibility of the tissue was estimated through measurement of the tissue lysate (n=25). The iron level was measured (in milligrams of iron per gram of wet tissue) with chemical analysis after MR imaging. While 1/T2 and magnetic susceptibility are not equivalent measures of the chemically determined tissue iron level, correlations were expected and were identified by using linear regression models. RESULTS: Iron concentration range was 0.28-1.95 mg/g wet tissue. Iron concentration was strongly correlated with 1/T2 (r=0.92, P <.001, and the root of the mean squares error of the linear prediction, epsilonRMS, was 0.17 mg Fe/g wet tissue with a repetition time of 700 msec). Iron concentration also was strongly correlated with magnetic susceptibility (r=0.90, P <.001, epsilonRMS=0.19 mg Fe/g wet tissue). Multiple regression analysis with combined 1/T2 (with repetition time of 700 msec) and magnetic susceptibility data led to a slight increase in r and decrease in epsilon(RMS) (r=0.93, P <.001, epsilonRMS=0.16 mg Fe/g wet tissue). CONCLUSION: The results of this animal model study demonstrate that 1/T2 and magnetic susceptibility values can be used for estimation of the iron level in the heart.

Animals↗

PubMed1983

Ferritin in the red cells of normal subjects and patients with iron deficiency and iron overload.

Red cell ferritin was measured in normal subjects and patients with iron deficiency and iron overload by means of radioimmunoassays with antibodies to liver (basic) and heart (acidic) ferritins. In most of the subjects examined, red cells were found to contain greater amounts of heart-type than liver-type ferritin. The basic ferritin content reflected the abnormal body iron status both in iron deficiency and iron overload while the acidic ferritin content was less closely related to the iron status. The two immunologically different red-cell ferritins probably represent distinct ferritin molecules and may have different metabolic functions within haem-synthesizing erythroid cells.

Anemia, Aplastic↗

PubMed1994

Selective iron deposition in pancreatic islet B cells of transfusional iron-overloaded autopsy cases.

Pancreatic islets of 36 autopsy cases with transfusional iron-overload were examined. Immunohistochemical and histochemical stainings were used to clarify the relationship between blood transfusion and iron deposition in the islet. Disease of the lymphohemopoietic system (leukemia, lymphoma, aplastic anemia) or liver (carcinoma and/or cirrhosis) accounted for 86.1% of the patients' main diagnosis. Sixteen of them had slight hemosiderin deposition (Group 1), twenty cases had severe hemosiderin deposition (Group 2). Another ten cases were used as controls (Group 3). The cases had a similar age distribution to Group 1 and 2, with neither blood transfusion nor hemosiderin deposition. The volume of blood transfusion was 6.1 +/- 3.6, 17.5 +/- 12.2 L for Groups 1 and 2, respectively. The plasma glucose was 137.8 +/- 54.4 and 170.6 +/- 108.4 mg/dL, respectively. Four cases in Group 1 and 14 cases in Group 2 had glycosuria. The number of islet cells with hemosiderin increased with the enlargement of transfusion volume (r = 0.664, P < 0.001). Plasma glucose also related with the percentage of hemosiderin positive islet cell (r = 0.386, P < 0.025). In severely iron-overloaded cases, hemosiderin was selectively deposited in B cells of the islet. It was concluded that large amounts of blood transfusions for non-congenital disease can induce selective hemosiderin deposition and impairment of pancreatic B cell that may result in hyperglycemia and diabetes mellitus of the patients.

Adult↗

PubMed2003

Health implications of iron overload: the role of diet and genotype.

The relationship between high dietary iron intake, mutations of the HFE gene, and iron status, and their effects on human health are reviewed. Prolonged high dietary intakes of iron are unlikely to result in iron overload in the general population. Homozygotes for the C282Y mutation of the HFE gene have elevated body iron levels. Heterozygotes have normal iron stores but some may be at increased risk for cardiovascular disease. There is no convincing evidence that elevated iron status increases the risk of coronary heart disease or type 2 diabetes, but high iron intakes may increase the risk of colorectal cancer. The dietary levels of iron associated with health risks in different HFE genotypes must be determined.

Adult↗

PubMed2001

Expression of CD2 and activation markers on blood T-helper cell subsets in patients with transfusional iron overload.

The aim of the present study was to investigate the relationship between different measures of iron status, and the expression of CD2, and the activation markers CD25, CD71, CD45RO, HLADR CD38 within the Th-cell subset in patients with progressive transfusional iron overload. We estimated the expression of the activation surface markers on the Th cells of peripheral blood by flow cytometry from 22 multiply transfused patients. The number of CD2 binding sites (BS) on Th cells was significantly higher in the patients (82 917 +/- 30 801) than in age-matched normal controls (41 145 +/- 6989, P < 0.0001). When investigating whether this difference could be due to the iron overload we found the number of CD2 BS closely related to the iron saturation of serum transferrin (TfS) (R2 = 0.78, P < 0.001). The relationship to the serum ferritin concentration and to the number of blood units given was weaker, but also significant (R2 = 0.22, P < 0.027, respectively, R2 = 0.21, P < 0.032). Also the fraction of mature memory Th cells which express CD45RO at a high level was directly related to the TfS (R2 = 0.57, P < 0.0001), while the expression of CD38 within the Th cell fraction was inversely related to the TfS (R2 = - 0.43, P = 0.009). The expression of HLA-DR (but not of CD25 and CD71) was also directly related to the TfS (R2 = 0.29, P = 0.01). Our results show a clear, statistical relationship between the iron status and the expression of surface markers within Th cells in multiply transfused patients.

ADP-ribosyl Cyclase↗

PubMed1990

Treatment of transfusional iron overload.

Advances in the treatment of iron overload hold the promise of making long-term transfusion therapy a safer approach to the management of thalassemia major, sickle cell disease, and numerous other hematologic disorders. The responsibility now placed on the treating physician is to monitor iron stores carefully, to begin chelation therapy at an appropriate time, and to encourage regular use of deferoxamine. For the clinical investigator, the success of chelation therapy with deferoxamine should prompt an intensive search for new chelators. These new chelators should be not only effective but also inexpensive, readily available, safe, and easy to administer.

Administration, Oral↗

PubMed1990

Non-invasive quantitation of liver iron-overload by magnetic resonance imaging.

A standard magnetic resonance imaging (MRI) system allowing spin echo times of 10 ms was used to quantitate liver iron concentration in nine healthy normal subjects and 13 patients with various grades of iron overload. Body iron status was estimated by measuring the serum ferritin concentration. In 11 subjects (two normal healthy controls, eight patients with HLA-related hereditary haemochromatosis and one patient with thalassaemia major) non-haem hepatic iron concentration was determined chemically in biopsy specimens (dry weight), in parallel to serum ferritin and MRI-T2 relaxation times. A moderate correlation (r = 0.79) was obtained for the correlation of the T2-relaxation rate (1/T2) and serum ferritin of the 22 subjects investigated. A much closer correlation (r = 0.98) was observed for the 1/T2 liver iron relationship in the 10 subjects analysed by liver biopsy. It is concluded from these preliminary observations, that MR-imaging may provide a useful non-invasive tool for the quantitative determination of liver iron in iron overload-syndromes.

Adult↗

PubMed2003

Pharmacotherapy of iron overload in thalassaemic patients.

The recommended treatment for thalassaemia major is regular blood transfusions, although these lead to the harmful accumulation of iron in the body. If untreated, iron overload is responsible for heart, liver and endocrine diseases. The only two iron chelating agents available for the treatment of iron overload are deferoxamine and deferiprone. The standard iron chelation therapy is based on the use of deferoxamine. Although this drug was introduced in the 1970s, it still remains the treatment of choice. Recently, another iron chelator, deferiprone, became available for clinical use in the European Community. Deferiprone is indicated as second-line treatment in patients with thalassaemia major, for whom deferoxamine therapy is contraindicated or in patients who present with serious toxicity to deferoxamine therapy. This paper examines this chelating agent and compares it with deferoxamine in order to ascertain the current and potential contribution of deferiprone to the treatment of thalassaemic patients.

Clinical Trials as Topic↗

PubMedDate not supplied

MR evaluation of liver iron overload.

Children and young adults with hemolytic anemias requiring frequent transfusions develop increased liver iron content. We evaluated 15 chronically transfused children with sickle cell disease to determine whether spin-echo magnetic resonance (MR) imaging was useful in assessing the degree of iron overload. Quantitative MR parameters were correlated with liver biopsy iron determinations and serum ferritin levels. The best predictor of liver iron was the ratio of the intensities between the liver and paraspinal musculature on somewhat T1 weighted sequence (repetition time 0.5 s, echo time 28 ms), R2 = 0.58. Magnetic resonance was able to separate those patients with liver iron levels greater than 100 micrograms/mg (intensity ratios approximately 0.4), from those with levels less than 100 micrograms/mg (intensity ratios near 1). However, MR was unable to quantitate liver iron in patients with values ranging from 100 to 400 micrograms/mg since similar intensity ratios were present in this range. Thus, MR provides a qualitative rather than quantitative assessment of liver iron overload.

Anemia, Sickle Cell↗

PubMed1989

[The functions of iron in the defense against infections, and especially the importance of abnormalities in phagocytosis in iron overload].

The biological functions of iron result from its catalytic properties and from its ability to stimulate the formation of potentially toxic oxydant radicals. In living organisms, both properties are modulated or controlled by the interactions of the metal with specific proteins. Essential element for both man and pathogenic germs, iron exerts many functions which are crucial in the defence against infections. Both host and microorganisms possess mechanisms allowing them to harvest iron. Furthermore, the potential biological toxicity of the metal is utilized in the host's phagocytes. Iron deficiency and overload lead to complex alterations of these mechanisms and may predispose to some infections. One of these abnormalities concerns the phagocytosis of the polymorphonuclear neutrophils observed in iron overload. Recent studies conducted by our group confirm the hypothesis that these functional disturbances of polymorphonuclear neutrophils may be due to the autotoxicity of non protein bound iron.

Antibody Formation↗

PubMed2000

Concentration of iron and distribution of iron and transferrin after experimental iron overload in rat tissues in vivo: study of the liver, the spleen, the central nervous system and other organs.

The purpose of this study was to estimate the iron concentration in the liver, spleen and brain of control rats and rats overloaded with iron and to determine the distribution of iron and of transferrin (TF). Iron was administered to Wistar rats by food supplemented with 3% carbonyl iron for 3 months, or intraperitoneally, or intraveneously as iron polymaltose for 4 months (total administered dose: 300 or 350 mg/rat, respectively). Iron concentration was estimated by atomic absorption spectrophotometry and iron- and TF-distribution histochemically and immunohistochemically, respectively. In control rats the organ with the highest iron content was the spleen, followed by the liver and brain. After iron loading the increase of iron in the liver was greater than that of the spleen; iron concentration in the brain did not change significantly. Distribution of iron in the liver was in Kupffer cells throughout the lobule and in hepatocytes at its periphery. No difference in the number of positive cells or staining intensity for TF was observed between control rats and iron overloaded animals in the liver or central nervous system (CNS); the spleen was negative for TF. Distribution of TF in the liver showed a centrilobular localisation in hepatocytes. TF reaction in the brain occurred in oligodendrocytes, vessel walls, choroid plexus epithelial cells and some neurons. In conclusion, experimental iron overload in rats leads to iron uptake mainly by reticuloendothelial (RE) cells and hepatocytes, indicating that hepatocytes are of particular importance for iron metabolism. Iron uptake by the brain was not significant, probably because the brain is protected against iron overload. Iron overload did not influence location and quantity of TF in the liver and CNS, whereas the visualisation of iron and TF did not coincide. This indicates that TF may have other functions beyond iron transport.

Animals↗

PubMed1985

The effect of iron overload on urinary excretion of immunoreactive prostaglandin E2.

The effect of in vivo lipid peroxidation on the excretion of immunoreactive prostaglandin E2 (PGE2) in the urine of rats was studied. Weanling, male Sprague-Dawley rats were fed a vitamin E-deficient diet containing 10% tocopherol-stripped corn oil (CO) or 5% cod liver oil (CLO) with or without 40 mg dl-alpha-tocopheryl acetate/kg. To induce a high, sustained level of lipid peroxidation, some rats were injected intraperitoneally with 100 mg of iron as iron dextran after 10 days of feeding. Iron overload stimulated in vivo lipid peroxidation in rats, as measured by the increase in expired ethane and pentane. Dietary vitamin E reversed this effect. Rats fed the CLO diet excreted 9.5-fold more urinary thiobarbituric acid-reactive substances (TBARS) than did rats fed the CO diet. Iron overload increased the excretion of TBARS in the urine of rats fed the CO diet, but not in urine of rats fed the CLO diet. Dietary vitamin E decreased TBARS in the urine of rats fed either the CO or the CLO diet. Iron overload decreased by 40% the urinary excretion of PGE2 by rats fed the CO diet, and dietary vitamin E did not reverse this effect. Iron overload had no statistically significant effect on urinary excretion of PGE2 by rats fed the CLO diet. A high level of lipid peroxidation occurred in iron-treated rats, as evidenced by an increase in alkane production and in TBARS in urine in this study, and by an increase in alkane production by slices of kidney from iron-treated rats in a previous study [V. C. Gavino, C. J. Dillard, and A. L. Tappel (1984) Arch. Biochem. Biophys. 233, 741-747]. Since PGE2 excretion in urine was not correlated with these effects, lipid peroxidation appears not to be a major factor in renal PGE2 flux.

Animals↗

PubMed1984

Iron overload and left ventricular performance in beta thalassemia.

The effect of iron overload on left ventricular (LV) performance was studied in 60 patients with beta-thalassemia. Patients were divided into 3 groups according to the number of blood units (BU) received. Clinically, 14 patients were in advanced classes (III and IV) of congestive heart failure (CHF). LV performance was extensively studied by M-mode echocardiography, and the results were correlated to BU transfused and CHF presence. E point-septal separation, LV systolic and diastolic dimensions had greater values in CHF patients (p less than 0.0001). The percentage shortening of the internal LV diameter and the peak velocity of circumferential fiber shortening were reduced in CHF patients (p less than 0.01 and 0.0001), while the percentage thickening of the LV posterior wall (PW) and interventricular septum (IVS), were independent of CHF presence. LVPW relaxation and indices of the overall diastolic LV function had similar values in all groups. The relation of all systolic and diastolic indices to BU was low (r less than 0,6) and in most cases indifferent (p:NS). A special finding was observed in 4 CHF patients, where segmental IVS dyskinesia contrasted with a satisfactory LVPW motion. The above results indicate that CHF in beta-thalassemia is not the consequence of volume and iron overload, but that these factors are predisposing towards the development of a specific type of cardiomyopathy.

Adolescent↗