Search PubMed⌕ Search

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.

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

At least 109 records · Page 6Linked to original sources
PubMed1999

Long-term follow-up after liver transplantation in patients with hepatic iron overload.

Patients with hepatic iron overload who undergo orthotopic liver transplantation (OLT) have a worse 1-year survival than those who undergo transplantation for other indications; the long-term outcome in this population is unknown. The purpose of this study is to report long-term follow-up after OLT in a cohort of patients with hepatic iron overload. Five liver transplant centers in the United States reported follow-up data on 37 patients receiving a first liver transplant who had severe hepatic iron overload in their native livers. Kaplan-Meier 5-year survival among these patients was compared with survival data from all age-matched liver transplantations reported to the United Network for Organ Sharing (UNOS) over the same time period (1987 to 1993). The 5-year survival rate after OLT was 40% in the hepatic iron overload group compared with an overall survival rate of 62% for all patient groups from the UNOS registry (P =.0009). Although sepsis was the cause of 53% of all deaths occurring within the first year after OLT, cardiac complications accounted for 50% of the late mortality in patients with hepatic iron overload. In conclusion, long-term survival after OLT is significantly decreased in patients with hepatic iron overload. Infectious and cardiac complications are the most common causes of death in these patients. Further studies are needed to define the relationship between hepatic iron overload and mortality and to examine the effect of iron depletion on outcome after OLT in this patient population.

Cause of Death↗
PubMed2002

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

BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: These results suggest that in iron overloaded liver, haemosiderin consists predominantly of denatured H-ferritin subunits.

Adult↗
PubMedDate not supplied

[Iron overload disease: recent findings].

Iron overload diseases are due to a progressive increase in total body iron stores that leads to deposition of iron in parenchymal organs and to subsequent damage to these organs. The commonest inherited form of iron overload is hereditary hemochromatosis (HH), an autosomal recessive disorder affecting the white population. Although in the western world and in northern Europe the majority of cases of HH are associated with an HFE gene mutation (C282Y and H63D), there are families with a familial iron overload disorder in whom neither the C282Y nor the H63D mutations were found. Recently, other forms of HH that are not related to HFE, but are due to mutations in genes coding iron transport proteins (ferroportin-1, TfR2, hepcidin) have been described. The clinical presentation of the disorder is highly variable, depending on the severity of iron overload. In fact, the inappropriate absorption and deposition of dietary iron may result in the development of hepatic and non-hepatic end-organ injury, leading to liver cirrhosis, hepatocellular carcinoma, diabetes, arthritis, skin pigmentation and cardiac diseases. HH and its sequelae are preventable with an early diagnosis and treatment. Patients with evidence of iron overload, a family history of HH or other risk factors should be screened by genotype testing for the HFE mutation. Nowadays, HH is recognized as being a complex genetic disease with probable significant environmental and genetic modifying factors, such as hepatitis C virus infection and alcohol abuse, and it has been shown that HFE mutations represent an independent risk factor for fibrosis and cirrhosis in chronic hepatitis C.

Algorithms↗
PubMed2003

L-type Ca2+ channels provide a major pathway for iron entry into cardiomyocytes in iron-overload cardiomyopathy.

Under conditions of iron overload, which are now reaching epidemic proportions worldwide, iron-overload cardiomyopathy is the most important prognostic factor in patient survival. We hypothesize that in iron-overload disorders, iron accumulation in the heart depends on ferrous iron (Fe2+) permeation through the L-type voltage-dependent Ca2+ channel (LVDCC), a promiscuous divalent cation transporter. Iron overload in mice was associated with increased mortality, systolic and diastolic dysfunction, bradycardia, hypotension, increased myocardial fibrosis and elevated oxidative stress. Treatment with LVDCC blockers (CCBs; amlodipine and verapamil) at therapeutic levels inhibited the LVDCC current in cardiomyocytes, attenuated myocardial iron accumulation and oxidative stress, improved survival, prevented hypotension and preserved heart structure and function. Consistent with the role of LVDCCs in myocardial iron uptake, iron-overloaded transgenic mice with cardiac-specific overexpression of the LVDCC alpha1-subunit had twofold higher myocardial iron and oxidative stress levels, as well as greater impairment in cardiac function, compared with littermate controls; LVDCC blockade was again protective. Our results indicate that cardiac LVDCCs are key transporters of iron into cardiomyocytes under iron-overloaded conditions, and potentially represent a new therapeutic target to reduce the cardiovascular burden from iron overload.

Amlodipine↗
PubMed1993

Chronic feeding of carbonyl-iron and TMH-ferrocene in rats. Comparison of two iron-overload models with different iron absorption.

1. The use of carbonyl-iron and (3,5,5-trimethylhexanoyl)-ferrocene (TMH-ferrocene) as a dietary iron-overload model was studied in rats using 59Fe-labelled compounds. 2. The intestinal absorption of carbonyl-iron but not from the TMH-ferrocene-iron was dependent upon the dosage and downregulated in iron-loaded rats. 3. In both models, and similar to hereditary haemochromatosis in humans, the storage of excess iron in the liver started in hepatocytes, whereas the range of iron-loading was strikingly different. 4. Because of the fast and progressive iron-loading, the TMH-ferrocene-model is the most encouraging animal model for experimental haemochromatosis.

Administration, Oral↗
PubMed1979

Iron overload despite partial gastrectomy.

Iron overload was found in 3 patients who had undergone partial gastrectomy: a 61-year-old woman developed iron overload because she may have had idiopathic haemochromatosis and had also been given parenteral iron; in a 62-year-old man with thalassaemia minor, iron overload may have developed because of increased oral iron ingestion, low serum folate, increased, albeit ineffective, erythropoiesis and sideroblastic anaemia; a 74-year-old man with thalassaemia minor developed iron overload without exogenous therapy and died from a hepatoma. These cases illustrate that partial gastrectomy fails to protect patients from developing iron overload, particularly if given uncontrolled iron therapy.

Aged↗
PubMed2000

Iron overload and kidney lysosomes.

Iron overload has been associated with damage of the liver and other organs of patients with primary or secondary increased iron load. In order to study the effect of iron overload on the pathophysiology of kidney lysosomes, experimentally induced iron overload models were employed. Iron overload was achieved through intraperitoneal injections of Fe-dextran (Imferon) in male rats, at different final iron concentrations (825 and 1650 mg/kg, single and double dose groups respectively). Controls were injected with dextran following a similar protocol. The animals were killed at different time points after the last injection. Subcellular fractionation studies of kidney homogenates were carried out by differential centrifugation and density gradient centrifugation. The kidney iron load was increased with both doses. Iron appeared to accumulate mainly in the lysosomes, bringing about distinct changes in the behaviour of the organelles as judged by subcellular fractionation studies. Lysosomes became more fragile and showed increased density. The extent of the above changes seemed to correlate with the extent and duration of iron accumulation and could be reversed when the iron load was reduced.

Animals↗
PubMed1999

Insulin resistance-associated hepatic iron overload.

BACKGROUND & AIMS: Hepatic iron overload has been reported in various metabolic conditions, including the insulin-resistance syndrome (IRS) and nonalcoholic steatohepatitis (NASH). The aim of this study was to show that such hepatic iron overload is part of a unique and unrecognized entity. METHODS: A total of 161 non-C282Y-homozygous patients with unexplained hepatic iron overload were included. We determined the age; sex; presence of IRS (1 or more of the following: body mass index of >25, diabetes, or hyperlipidemia); serum iron tests and liver iron concentration (LIC; reference value, <36 micromol/g); liver function test results; C282Y and H63D HFE mutations; and liver histological status. RESULTS: Patients were predominantly male and middle-aged. Most (94%) had IRS. Transferrin saturation was increased in 35% (median, 42%; range, 13%-94%). LIC ranged from 38 to 332 micromol/g (median, 90 micromol/g), and LIC/age ratio ranged from 0.5 to 4.8 (median, 1.8). Allelic frequencies of both HFE mutations were significantly increased compared with values in normal controls (C282Y, 20% vs. 9%; H63D, 30% vs. 17%), only because of a higher prevalence of compound heterozygotes. Patients with no HFE mutations had similar degrees of iron overload as those with other genotypes, except for compound heterozygotes, who had slightly more iron burden. Steatosis was present in 25% of patients and NASH in 27%. Portal fibrosis (grades 0-3) was present in 62% of patients (grade 2 or 3 in 12%) in association with steatosis, inflammation, and increased age. Sex ratio, IRS, transferrin saturation, and LIC did not vary with liver damage. Serum ferritin concentration, liver function test results, and fibrosis grade were more elevated in patients with steatosis and NASH than in others, but LIC and allelic frequencies of HFE mutations were similar. CONCLUSIONS: This study shows that patients with unexplained hepatic iron overload are characterized by a mild to moderate iron burden and the nearly constant association of an IRS irrespective of liver damage.

Adult↗
PubMed1992

Salivary iron status in children with iron deficiency and iron overload.

Forty anaemic (iron deficiency anaemia-27, thalassemia major-8, and aplastic anaemia-5) and 10 non-anaemic children (serving as controls) aged from 8 months to 10 years were selected for the study. The salivary iron was significantly higher in iron deficient and iron overload conditions compared to controls. The mean salivary:serum iron ratio was same in control and iron overload cases, while it was twice as high in iron deficient anaemic children. The correlation between salivary iron and serum iron was significant (r = 0.7392, P less than 0.001) in these cases. The iron deficient anaemic children with hypoalbuminaemia had significantly reduced serum and salivary protein (P less than 0.001), but iron concentrations in serum and saliva remained unaltered. The salivary protein level had significant correlations with serum albumin and serum protein (P less than 0.001). Thus, the iron in saliva is maintained at a higher level and more so in iron deficiency anaemia; it correlates well with serum iron (r = 0.6853, P less than 0.001) in iron deficient anaemic children also and is not affected by co-existing hypoproteinaemic situation.

Albumins↗
PubMed1996

Genetic hemochromatosis in Italian patients with porphyria cutanea tarda: possible explanation for iron overload.

BACKGROUND/AIMS: Mild to moderate iron overload is found in most patients with porphyria cutanea tarda. This study aimed to evaluate whether iron overload in patients with porphyria cutanea tarda is related to the presence of a coexistent genetic hemochromatosis gene. METHODS: A cohort study of 94 Italian patients with porphyria cutanea tarda (90 men and 4 women) and 20 relatives of five patients with iron overload were studied. Diagnosis of iron overload was assessed by transferrin saturation, serum ferritin and iron removed by phlebotomy to reach depletion. HLA typing by microlymphocytotoxicity test and duodenal ferritin analysis by immunohistochemistry were performed in a smaller number of patients. The chi square test was used to compare means and prevalences. RESULTS: Iron overload was present in 62% of the patients. HLA-A3 prevalence was significantly higher (p < 0.01) in subjects with iron overload than in those without. A lack of duodenal ferritin was observed in 14/18 patients with and in 6/12 without iron overload. Family studies showed the presence of iron overload but not of porphyria cutanea tarda in HLA identical or semi-identical relatives of the patients. CONCLUSIONS: Italian patients with porphyria cutanea tarda and iron overload appear to have one or even two genes for genetic hemochromatosis.

Adult↗
PubMed1991

Iron overload: detection using a micromethod for iron-binding capacity.

Depending upon the transferrin saturation value, 214 serum samples were divided into three groups--iron overloaded (46 cases), iron deficient (61 cases) and normal (107 cases)--and tested with a micromethod based upon detection of unsaturated iron binding capacity. All the samples with iron overload could be distinguished from the other two groups, the results of the normal and iron deficient groups showing wide scatter and overlap. The high prevalence of iron deficiency anaemia and thalassaemia (iron overload) syndromes in India and other developing countries emphasises the need to differentiate these disorders at the earliest opportunity. The micromethod can be of immense help as it is a simple, rapid and inexpensive.

Anemia, Hypochromic↗
PubMed2000

Effects of iron overload on the immune system.

Iron and its binding proteins have immunoregulatory properties, and shifting of immunoregulatory balances by iron excess or deficiency may produce severe, deleterious physiological effects. Effects of iron overload include decreased antibody-mediated and mitogen-stimulated phagocytosis by monocytes and macrophages, alterations in T-lymphocyte subsets, and modification of lymphocyte distribution in different compartments of the immune system. The importance of iron in regulating the expression of T-lymphocyte cell surface markers, influencing the expansion of different T-cell subsets, and affecting immune cell functions can be demonstrated in vitro and in vivo. The poor ability of lymphocytes to sequester excess iron in ferritin may help to explain the immune system abnormalities in iron-overloaded patients. Iron overload as seen in hereditary hemochromatosis patients enhances suppressor T-cell (CD8) numbers and activity, decreases the proliferative capacity, numbers, and activity of helper T cells (CD4) with increases in CD8/CD4 ratios, impairs the generation of cytotoxic T cells, and alters immunoglobulin secretion when compared to treated hereditary hemochromatosis patients or controls. A correlation has recently been found between low CD8+ lymphocyte numbers, liver damage associated with HCV positivity, and severity of iron overload in beta-thalassemia major patients. Iron overload, with its associated increases of serum iron levels and transferrin saturation, may cause a poor response to interferon therapy. Iron overload with hyperferremia is associated with suppressed functions of the complement system (classic or alternative types). High plasma ferritin content in patients with chronic, diffuse diseases of the liver (cirrhosis, chronic hepatitis), beta-thalassemia major, dyserythropoiesis, and hereditary hemochromatosis may induce the development of anti-ferritin antibodies with the production of circulating immune complexes. Increased body stores of iron in various clinical situations may tip the immunoregulatory balance unfavorably to allow increased growth rates of cancer cells and infectious organisms, and complicate the clinical management of preexisting acute and chronic diseases.

B-Lymphocytes↗
PubMed1989

[Treatment of post-transfusion iron overload by deferoxamine].

Iron chelation therapy must be associated with the regular blood transfusions required for thalassaemia and other chronic anemias. We report here a study concerning 4 groups of patients, aged 6 to 28, regularly transfused at Necker Enfants-Malades hospital: a) 20 with thalassaemia major; b) 6 with thalassaemia intermedia; c) 2 with sickle cell disease and d) 2 with Blackfan-Diamond syndrome. The transfusion regimen consisting of monthly or quarterly transfusions varied as a function of the groups. Desferal was used in all patients. The dosage and the route of administration (IV, IM, SC) were adapted to the amount of iron transfused and to the nature of the disease. The serum ferritin level was considered as the indicator of the iron overload. Comparisons were established between the quantities of iron transfused, ferritin levels, and parameters such as dosage, route of administration and compliance to Desferal. During the period of study 3 patients died from cardiac failure due to transfusional hemosiderosis. Endocrine complications (diabetes 2 cases, hypocalcemia 3 cases, hypothyroidism 1 case and delayed puberty 7 cases) were observed. This high incidence of complications induced by post-transfusional iron overload has recently prompted us to improve the quality of chelation therapy through the use of the services of a specialized center where patients as well as their families can be trained more adequately in home care and self-treatment.

Adolescent↗
PubMed1995

Iron overload in African Americans.

PURPOSE: Iron overload unexplained by dietary or medicinal iron excess, transfusion, or sideroblastic anemia has been described infrequently in Americans of African descent. The purpose of this study was to characterize iron overload attributable to excessive iron absorption in African Americans. PATIENTS AND METHODS: In a community hematology and medical oncology practice during the interval 1990 to 1993, we identified and evaluated a series of cases comprised of 6 men and 1 woman, with a mean age of 55 +/- 14 (SD) years (range 33 to 69). Data on clinical features, serum iron parameters, liver and body iron stores, evaluations of anemia, human leukocyte antigen (HLA) typing, and family studies were analyzed. RESULTS: Among our patients, the serum iron parameters were: iron concentration 26 +/- 13 mumol/L, transferrin saturation 59 +/- 21%, and ferritin concentration 1,588 +/- 1,053 micrograms/L. Clinical abnormalities observed included weakness and fatigue, decreased libido and impotence, hepatopathy, arthropathy, diabetes mellitus, hypogonadotrophic hypogonadism, and hyperpigmentation. Hepatic parenchymal cell iron deposits were increased in each of the 6 patients studied, and Kupffer cell iron deposits were prominent in 4. The occurrence of iron overload was verified by liver iron quantification and therapeutic phlebotomy. Four subjects had alpha-thalassemia minor; 2 others had hemoglobin S and C traits. No proband had HLA-A3 positivity. Four probands had other family members with iron overload. CONCLUSIONS: In comparison with Caucasians with hemochromatosis, our patients have slightly lower mean values of serum iron concentration and transferrin saturation, more Kupffer cell iron deposits, a higher incidence of thalassemia and hemoglobinopathy, and infrequent positivity for HLA-A3. Iron overload in African Americans appears to be more similar to that in certain sub-Saharan African natives than to hemochromatosis.

Adult↗
PubMed1987

[Serum ferritin in iron overload].

Even with uncomplicated iron overload, serum ferritin which can be identified in the circulating blood by sensitive immunochemical methods has a direct and quantitative correlation to the iron stored in the organism. The relation of stored iron and serum ferritin is not linear, but has an exponential character. The diagnostic function of serum ferritin as an indicator of stored iron, however, is virtually not influenced by it. The indications listed in Tab. 3 can be demarcated for diagnostic application in cases of iron overload. Hitherto, the molecular microheterogenicity of serum ferritin has exercised no essential impact on its diagnostic application. High ferritin concentrations may arise in the circulating blood by a number of disease processes listed in Tab. 4, without the simultaneous existence of a respective iron overload of the tissue. These correlations have to be observed in the diagnostic application of determining serum ferritin as well as in methodical possibilities of fault (high dose hook effect), thus limiting the use of serum ferritin as an indicator of stored iron both in case of iron overload and iron deficiency. As in all isolated laboratory investigations, all other clinical and chemical laboratory information available about the individual patient has to be taken into account in each case for interpreting the serum ferritin concentration.

Adult↗
PubMed2003

Strategy for diagnosis and management in iron overload.

When suspecting an iron overload condition, the transferrin saturation levels should be determined. Levels higher than 45% and serum ferritin in men and postmenopausal women exceeding 200 microg/l confirm the iron overload. Afterwards, the HFE protein genotype should be determined. If it is C282Y or C282Y/H63D, the diagnosis of hereditary hemochromatosis can be accepted as the cause of the iron overload. In the absence of said genotypes, the overload is secondary or not related to the HFE protein. In hereditary hemochromatosis, the degree of iron overload and organic lesions must be established. Liver biopsies are very useful for obtaining said information and for the first case, the determination of serum ferritin is very useful. When less than 1000 microg/l, normal transaminases and no hepatomegalies, a treatment can be started without the need for a liver biopsy. In absence of anemia, the treatment is based on phlebotomies, 400-500 ml a week until obtaining depletion of excess iron. In presence of anemia, the treatment is based on chelating agents, preferably subcutaneous administered 8 hours a day.

Erythropoiesis↗
PubMed2004

Iron homeostasis and inherited iron overload disorders: an overview.

Iron is an ubiquitous metal of vital importance to the normal physiologic processes of many organisms. Recent discoveries of mutations in genes that lead to inherited iron overload diseases have advanced the understanding of iron homeostasis in humans. This article provides an overview of the human iron cycle, regulation of iron homeostasis, how perturbations in this homeostasis lead to iron overload disease in adults and children, and strategies for diagnosis of inherited iron overload.

Antimicrobial Cationic Peptides↗
PubMed2003

Genetic regulation of cell function in response to iron overload or chelation.

Iron influences many aspects of cell function on different biochemical levels. This review considers effects mediated through iron-dependent changes in gene expression in mammalian cells. Several classes of related genes are responsive to cellular iron levels, but no clear patterns readily account for the toxicity of iron overload or the consequences of removal of iron with chelating agents. Here we group some of the genes influenced by iron status into those related to iron metabolism, oxygen and oxidative stress, energy metabolism, cell cycle regulation, and tissue fibrosis. Iron excess and chelation do not generally result in a continuous or graded transcriptional response, but indicate operation of distinct mechanisms. An emerging concept is that iron signals through generation of reactive oxygen species to activate transcription factors such as NF-kappaB, whereas iron removal mimics hypoxia, perhaps by disrupting iron-based O(2) sensors and influencing gene expression through, e.g., the hypoxia-inducible factor, HIF-1. Heme and other metalloporphyrins have other distinct mechanisms for regulating transcription. Regulation of gene expression through iron-responsive elements in mRNAs coded by several genes is one of the best understood mechanisms of translational control.

Animals↗