Liver Iron Retention Estimated from Utilization of Oral and Intravenous Radioiron in Various Anemias and Hemochromatosis in Humans.

Patients with hereditary hemochromatosis and non-transfusion-dependent hereditary anemia develop predominantly liver iron-overload. We present a unique method allowing quantification of liver iron retention in humans during first-pass of Fe-labeled iron through the portal system, using standard ferrokinetic techniques measuring red cell iron uptake after oral and intravenous Fe administration. We present data from patients with iron deficiency (ID; N = 47), hereditary hemochromatosis (HH; N = 121) and non-transfusion-dependent hereditary anemia (HA; N = 40).

Iron Absorption in Iron-Deficient Women, Who Received 65 mg Fe with an Indonesian Breakfast, Is Much Better from NaFe(III)EDTA than from Fe(II)SO₄, with an Acceptable Increase of Plasma NTBI. A Randomized Clinical Trial.

Plasma non-transferrin-bound iron (NTBI) is potentially harmful due to the generation of free radicals that cause tissue damage in vascular and other diseases. Studies in iron-replete and iron-deficient subjects, receiving a single oral test dose of Fe(II)SO₄ or NaFe(III)EDTA with water, revealed that FeSO₄ was well absorbed when compared with NaFeEDTA, while only the Fe(II) compound showed a remarkable increase of NTBI. As NaFeEDTA is successfully used for food fortification, a double-blind randomized cross-over trial was conducted in 11 healthy women with uncomplicated iron deficiency.

Intracellular labile iron promotes firm adhesion of human monocytes to endothelium under flow and transendothelial migration: Iron and monocyte-endothelial cell interactions.

Monocyte infiltration across the endothelium is part of the innate immune response, however it may contribute to severity of chronic conditions. We have investigated the effects of iron on the cytokine-mediated recruitment of monocytes to the endothelium, using a physiological flow model and a monocyte transendothelial migration model. Under flow, iron loading to endothelial cells promoted an increased number of tumor necrosis factor-alpha-mediated firm arrest of human monocytes.

Severity of iron overload of proband determines serum ferritin levels in families with HFE-related hemochromatosis: the HEmochromatosis FAmily Study.

Background/aims: In families of patients with clinically detected hereditary hemochromatosis (HH) early screening has been suggested to prevent morbidity and mortality. Here, we aim to identify determinants for iron overload in first-degree family members of C282Y homozygous probands with clinically detected HH.

Methods: Data on HFE-genotype, iron parameters, demographics, lifestyle factors and health, were collected from 224 Dutch C282Y homozygous patients with clinically diagnosed HH and 735 of their first-degree family members (FDFM), all participating in the HEmochromatosis FAmily Study (HEFAS).

Mutations in the HFE gene and cardiovascular disease risk: an individual patient data meta-analysis of 53 880 subjects.

Background: Whether mutations in the hemochromatosis (HFE) gene increase cardiovascular disease risk is still undetermined. The main reason is the low frequency of the mutations, in particular of the compound C282Y/H63D genotype. We combined the data of 11 observational studies for an individual patient data meta-analysis.

Can iron chelators influence the progression of atherosclerosis?

Epidemiological studies and experimental data suggest iron involvement in atherosclerosis. The relation between iron and atherosclerosis is complex and remains contradictory. In thalassemia patients, non transferrin bound iron (NTBI) and free hemoglobin (Hb) are present in plasma and may accelerate atherogenesis, but its progression may be inhibited by iron chelators.

Iron deficiency and NRAMP1 polymorphisms (INT4, D543N and 3'UTR) do not contribute to severity of anaemia in tuberculosis in the Indonesian population.

Fe-deficiency anaemia is the most common cause of anaemia in developing countries. In these settings, many chronic infections, including tuberculosis (TB), are highly prevalent. Fe is an essential nutrient for both host and mycobacteria that play a pivotal role in host immunity and mycobacterial growth.

Risk of iron overload in carriers of genetic mutations associated with hereditary haemochromatosis: UK Food Standards Agency workshop.

The UK Food Standards Agency convened a group of expert scientists to review current research investigating diet and carriers of genetic mutations associated with hereditary haemochromatosis. The workshop concluded that individuals who are heterozygous for the C282Y mutation of the HFE gene do not appear to respond abnormally to dietary Fe and therefore do not need to change their diet to prevent accumulation of body Fe.

Hereditary hemochromatosis: genetic complexity and new diagnostic approaches.

Since the discovery of the hemochromatosis gene (HFE) in 1996, several novel gene defects have been detected, explaining the mechanism and diversity of iron-overload diseases. At least 4 main types of hereditary hemochromatosis (HH) have been identified. Surprisingly, genes involved in HH encode for proteins that all affect pathways centered around liver hepcidin synthesis and its interaction with ferroportin, an iron exporter in enterocytes and macrophages.

Non-transferrin-bound iron and risk of coronary heart disease in postmenopausal women.

Background: Epidemiological studies aimed at correlating coronary heart disease (CHD) with serum ferritin levels have thus far yielded inconsistent results. We hypothesized that a labile iron component associated with non-transferrin-bound iron (NTBI) that appears in individuals with overt or cryptic iron overload might be more suitable for establishing correlations with CHD.

Methods And Results: We investigated the relation of NTBI, serum iron, transferrin saturation, and serum ferritin with risk of CHD and acute myocardial infarction (AMI).

Endothelial activation and induction of monocyte adhesion by nontransferrin-bound iron present in human sera.

Nontransferrin-bound iron (NTBI) has been detected in iron overload diseases. This form of iron may exert pro-oxidant effects and modulate cellular function and inflammatory response. The present study has aimed to investigate the effects of serum NTBI on monocyte adherence to endothelium.

Bleomycin has antiviral properties against drug-resistant HIV strains and sensitises virus to currently used antiviral agents.

In this study we performed phenotypic assays to assess involvement of the cancer chemotherapeutic agent bleomycin (BLM) in replication inhibition of mutant HIV-1 viral strains. Three clinically relevant mutant HIV variants, including one containing the Q151M mutation conferring multinucleoside resistance, were equally as sensitive to BLM as the wild-type HXB2 strain. Long-term incubation of BLM with a wild-type HIV(Ba-L) strain did not alter the sensitivity of the strain to BLM (IC(50) of BLM 0.

Serum ferritin is a risk factor for stroke in postmenopausal women.

Background And Purpose: Iron is an essential element for the human body. It has, however, been suggested that excessive iron stores may increase the risk of vascular disease. So far, epidemiologic studies on stroke are sparse.

Intestinal over-expression of iron transporters induces iron overload in birds in captivity.

Hereditary hemochromatosis (HH) is a frequent genetic disease of older subjects of northern European descent. It is characterized by increased iron absorption and severe iron overloading in parenchymal organs. A similar disturbance of iron metabolism occurs in specific animal species in captivity.

Dietary haem iron and coronary heart disease in women.

Aims: A role for iron in the risk of ischaemic heart disease has been supported by in vitro and in vivo studies. We investigated whether dietary haem iron intake is associated with coronary heart disease (CHD) risk in a large population-based cohort of middle-aged women.

Methods And Results: We used data of 16 136 women aged 49-70 years at recruitment between 1993 and 1997.

Intracellular labile iron modulates adhesion of human monocytes to human endothelial cells.

Objective: Elevated iron stores and high plasma iron concentration have been linked to an increased risk of atherosclerosis. Iron may thereby affect the interaction of monocytes to endothelium, an initial event in the formation of atherosclerotic plaques.

Methods And Results: Addition of 10 mumol/L non-transferrin-bound iron to the incubation medium caused a 2-fold increase in monocyte adhesion to human umbilical vein endothelial cells (HUVECs).

Mechanism of inhibition of the human immunodeficiency virus type 1 by the oxygen radical generating agent bleomycin.

Alternative targets of attack of the human immunodeficiency virus (HIV) are necessary in light of infection persistence due to onset of resistance after conventional reverse transcriptase and protease inhibitor therapy. We have recently shown that the cancer chemotherapeutic agent bleomycin (BLM) dose-dependently inhibits HIV-1 replication. The mechanism of this viral inhibition in vitro was investigated.

Heterozygosity for the Cys282Tyr mutation in the HFE gene and the risk of colorectal cancer (Netherlands).

Background & Aims: Heterozygosity for the Cys282Tyr transition in the HFE-gene is associated with slightly increased iron levels and may therefore be a potential risk factor for colorectal cancer.

Methods: We studied the relationship between Cys282Tyr-heterozygosity and colorectal cancer using a case-control design. The 240 colorectal cancer cases and 635 controls in our study were derived from a prospective cohort study of 12,242 postmenopausal women, who were invited for an experimental breast cancer screening program in Utrecht, The Netherlands.