Influence of body iron store status and cigarette smoking on cadmium body burden of healthy Thai women and men

The influence of cigarette smoking, body iron store status and gender on cadmium (Cd) body burden was examined in a group of 197 healthy Thais with overall mean age of 30.5 year (19-47 year). The lowest, geometric mean, and the highest urinary Cd excretion rate was 0.04, 0.46 and 3.84 mug/g creatinine, respectively. The prevalence of low iron stores (serum ferritin

Pancreatic iron stores assessed by magnetic resonance imaging (MRI) in beta thalassemic patients

Purpose: To assess the correlation between MRI findings of the pancreas with those of the heart and liver in patients with beta thalassemia; to compare the pancreas T2* MRI results with glucose and ferritin levels and labile plasma iron (LPI). Materials and methods: We retrospectively evaluated chronically transfused patients, testing glucose with enzymatic tests, serum ferritin with chemiluminescence, LPI with cellular fluorescence, and T2* MRI to assess iron content in the heart, liver, and pancreas. MRI results were compared with one another and with serum glucose, ferritin, and LPI. Liver iron concentration (LIC) was determined in 11 patients' liver biopsies by atomic absorption spectrometry. Results: 289 MRI studies were available from 115 patients during the period studied. 9.4% of patients had overt diabetes and an additional 16% of patients had impaired fasting glucose. Both pancreatic and cardiac R2* had predictive power (p < 0.0001) for identifying diabetes. Cardiac and pancreatic R2* were modestly correlated with one another (r(2) = 0.20, p < 0.0001). Both were weakly correlated with LIC (r(2) = 0.09, p < 0.0001 for both) and serum ferritin (r(2) = 0.14, p < 0.0001 and r(2) = 0.03, p < 0.02, respectively). None of the three served as a screening tool for single observations. There is a strong log-log, or power-law, relationship between ratio of signal intensity (SIR) values and pancreas R2* with an r(2) of 0.91. Conclusions: Pancreatic iron overload can be assessed by MRI, but siderosis in other organs did not correlate significantly with pancreatic hemosiderosis. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Hemoglobin, iron metabolism and angiographic coronary artery disease (The Ludwigshafen Risk and Cardiovascular Health Study).

BACKGROUND Anemia has been shown to be a risk factor for coronary artery disease and mortality. The involvement of body iron stores in the development of CAD remains controversial. So far, studies that examined hemoglobin and parameters of iron metabolism simultaneously do not exist. METHODS AND RESULTS Hemoglobin and iron status were determined in 1480 patients with stable angiographic coronary artery disease (CAD) and in 682 individuals in whom CAD had been ruled out by angiography. The multivariate adjusted odds ratios (OR) for CAD in the lowest quartiles of hemoglobin and iron were 1.62 (95%CI: 1.22-2.16), and 2.05 (95%CI: 1.51-2.78), respectively compared to their highest gender-specific quartiles. The fully adjusted ORs for CAD in the lowest quartiles of transferrin saturation, ferritin (F) and soluble transferrin receptor (sTfR)/log10F index were 1.69 (95%CI: 1.25-2.27), 1.98 (95%CI: 1.48-2.65), and 1.64 (95%CI: 1.23-2.18), respectively compared to their highest gender-specific quartiles. When adjusting in addition for iron and ferritin the OR for CAD in the lowest quartiles of hemoglobin was still 1.40 (95%CI: 1.04-1.90) compared to the highest gender-specific quartiles. Thus, the associations between either iron status or low hemoglobin and CAD appeared independent from each other. The sTfR was only marginally associated with angiographic CAD. CONCLUSIONS Both low hemoglobin and iron depletion are independently associated with angiographic CAD.

Body iron is associated with cognitive executive planning function in college women

Evidence of the relationship between altered cognitive function and depleted Fe status is accumulating in women of reproductive age but the degree of Fe deficiency associated with negative neuropsychological outcomes needs to be delineated. Data are limited regarding this relationship in university women in whom optimal cognitive function is critical to academic success. The aim of the present study was to examine the relationship between body Fe, in the absence of Fe-deficiency anaemia, and neuropsychological function in young college women. Healthy, non-Anaemic undergraduate women (n 42) provided a blood sample and completed a standardised cognitive test battery consisting of one manual (Tower of London (TOL), a measure of central executive function) and five computerised (Bakan vigilance task, mental rotation, simple reaction time, immediate word recall and two-finger tapping) tasks. Women's body Fe ranged from - 4·2 to 8·1 mg/kg. General linear model ANOVA revealed a significant effect of body Fe on TOL planning time (P= 0.002). Spearman's correlation coefficients showed a significant inverse relationship between body Fe and TOL planning time for move categories 4 (r - 0.39, P= 0.01) and 5 (r - 0.47, P= 0.002). Performance on the computerised cognitive tasks was not affected by body Fe level. These findings suggest that Fe status in the absence of anaemia is positively associated with central executive function in otherwise healthy college women. Copyright © The Authors 2012.

Regulation of lipocalin 2 (Lcn2) gene expression by iron stores, anemia and inflammation

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Regulation of lipocalin 2 (Lcn2) gene expression by iron stores, anemia and inflammation

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Disordered vascular compliance in haemochromatosis

Background: A relationship may exist between body iron stores, endothelial dysfunction and overall cardiovascular risk.

Aims: To compare vascular compliance, biochemical endothelial function and antioxidant status between patients with homozygous hereditary haemochromatosis and healthy controls.

Methods: Haemochromatosis patients and healthy controls were recruited. Measures of vascular compliance were assessed by applanation tonometry. Serological markers of endothelial function (plasma lipid hydroperoxides, cell adhesion molecules), antioxidant levels (ascorbate, lipid soluble antioxidants) and high-sensitivity C-reactive protein (CRP) were also measured.

Results: Thirty-five hereditary haemochromatosis patients (ten females, mean age 54.6) and 36 controls (27 female, mean age 54.0) were recruited. Haemochromatosis patients had significantly higher systolic and diastolic blood pressures. Pulse wave velocity (PWV) was significantly higher in male haemochromatosis patients (9.90 vs. 8.65 m/s, p = 0.048). Following adjustment for age and blood pressure, male haemochromatosis patients continued to have a trend for higher PWVs (+1.37 m/s, p = 0.058). Haemochromatosis patients had significantly lower levels of ascorbate (46.11 vs. 72.68 lmol/L, p = 0.011), retinol (1.17 vs. 1.81 lmol/L, p = 0.001) and g-tocopherol (2.51 vs. 3.14 lmol/L, p = 0.011). However, there was no difference in lipid hydroperoxides (0.46 vs. 0.47 nmol/L, p = 0.94), cell adhesion molecule levels (ICAM: 348.12 vs. 308.03 ng/mL, p = 0.32 and VCAM: 472.78 vs. 461.31 ng/mL, p = 0.79) or high-sensitivity CRP (225.01 vs. 207.13 mg/L, p = 0.32).

Conclusions: Haemochromatosis is associated with higher PWVs in males and diminished antioxidants across the sexes but no evidence of endothelial dysfunction or increased lipid peroxidation.

Endothelial function, antioxidant status and vascular compliance in newly diagnosed HFE C282Y homozygotes

Purpose: This pilot study was aimed to establish techniques for assessing and observing trends in endothelial function, antioxidant status and vascular compliance in newly diagnosed HFE haemochromatosis during the first year of venesection.

Patients/methods: Untreated newly diagnosed HFE haemochromatosis patients were tested for baseline liver function, iron indices, lipid profile, markers of endothelial function, anti-oxidant status and vascular compliance. Following baseline assessment, subjects attended at 6-weeks and at 3, 6, 9 and 12-months for follow-up studies.

Results: Ten patients were recruited (M = 8, F = 2, mean age = 51 years). Venesection significantly increased high density lipoproteins at 12-months (1.25 mmol/L vs. 1.37 mmol/L, p = 0.01). However, venesection did not significantly affect lipid hydroperoxides, intracellular and vascular cell adhesion molecules or high sensitivity C-reactive protein (0.57 mu mol/L vs. 0.51 mu mol/L, p = 0.45, 427.4 ng/ml vs. 307.22 ng/ml, p = 0.54, 517.70 ng/ml vs. 377.50 ng/ml, p = 0.51 and 290.75 mu g/dL vs. 224.26 mu g/dL, p = 0.25). There was also no significant effect of venesection on anti-oxidant status or pulse wave velocity (9.65 m/s vs. 8.74 m/s, p = 0.34).

Conclusions: Venesection significantly reduced high density lipoproteins but was not associated with significant changes in endothelial function, anti-oxidant status or vascular compliance. Larger studies using this established methodology are required to clarify this relationship further. 

Association Between Circulating Electronegative Low-Density Lipoproteins and Serum Ferritin in Hemodialysis Patients: A Pilot Study

Background: Iron supplementation is a common recommendation to chronic kidney disease patients undergoing hemodialysis (HD). However, iron excess is closely associated with lipid peroxidation and, it is well known that electronegative low-density lipoproteins (LDL[-]) are present at higher plasma concentrations in diseases with high cardiovascular risk such as chronic kidney disease. Thus, the aim of this study was to investigate whether ferritin levels are associated with LDL(-) levels in HD patients. Design: This was a cross-sectional study. Setting: This study was conducted from a private clinic in Rio de Janeiro, Brazil. Patients: The study included 27 HD patients and 15 healthy subjects. Methods and Procedures: Twenty-seven HD patients (14 men, 58.6 +/- 10 years, 62.2 +/- 51.4 months on dialysis, and body mass index: 24.4 +/- 4.2 kg/m(2)) were studied and compared with 15 healthy individuals (6 men, 53.8 +/- 15.4 years, body mass index: 24.5 +/- 4.3 kg/m(2)). Serum LDL(-) levels were measured using the enzyme-linked immunosorbent assay method; ferritin levels by commercially available kits, and tumor necrosis factor-alpha, interleukin-6, monocyte chemoattractant protein-1, and plasminogen activator inhibitor-1 were determined with a multiplex assay kit manufactured by R&D Systems. Results: The HD patients presented higher LDL(-) and tumor necrosis factor-alpha levels (0.15 +/- 0.13 U/L and 5.9 +/- 2.3 pg/mL, respectively) than healthy subjects (0.07 +/- 0.05 U/L and 2.3 +/- 1.3 pg/mL, respectively) (P = .0001). The mean ferritin level in HD patients was 1,117.5 +/- 610.4 ng/mL, and 90% of patients showed ferritin levels exceeding 500 ng/mL. We found a positive correlation between LDL(-) and ferritin in the patients (r = 0.48; P = .01), and ferritin was a significant contributor to LDL(-) concentrations independent of inflammation. Conclusions: Excess body iron stores for HD patients was associated with signs of increased oxidative stress, as reflected by increased LDL(-) levels in HD patients. (C) 2012 by the National Kidney Foundation, Inc. All rights reserved.

Next-Generation Sequencing of Hereditary Hemochromatosis-Related Genes: Novel Likely Pathogenic Variants Found in the Portuguese Population

Hereditary hemochromatosis (HH) is an autosomal recessive disorder characterized by excessive iron absorption resulting in pathologically increased body iron stores. It is typically associated with common HFE gene mutation (p.Cys282Tyr and p.His63Asp). However, in Southern European populations up to one third of HH patients do not carry the risk genotypes. This study aimed to explore the use of next-generation sequencing (NGS) technology to analyse a panel of iron metabolism-related genes (HFE, TFR2, HJV, HAMP, SLC40A1, and FTL) in 87 non-classic HH Portuguese patients. A total of 1241 genetic alterations were detected corresponding to 53 different variants, 13 of which were not described in the available public databases. Among them, five were predicted to be potentially pathogenic: three novel mutations in TFR2 [two missense (p.Leu750Pro and p.Ala777Val) and one intronic splicing mutation (c.967-1G>C)], one missense mutation in HFE (p.Tyr230Cys), and one mutation in the 5'-UTR of HAMP gene (c.-25G>A). The results reported here illustrate the usefulness of NGS for targeted iron metabolism-related gene panels, as a likely cost-effective approach for molecular genetics diagnosis of non-classic HH patients. Simultaneously, it has contributed to the knowledge of the pathophysiology of those rare iron metabolism-related disorders.

Next-generation sequencing of hereditary hemochromatosis-related genes: novel likely pathogenic variants found in the Portuguese population

Hereditary hemochromatosis (HH) is an autosomal recessive disorder characterized by excessive iron absorption resulting in pathologically increased body iron stores. It is typically associated with common HFE gene mutation (p.Cys282Tyr and p.His63Asp). However, in Southern European populations up to one third of HH patients do not carry the risk genotypes. This study aimed to explore the use of next-generation sequencing (NGS) technology to analyse a panel of iron metabolism-related genes (HFE, TFR2, HJV, HAMP, SLC40A1, and FTL) in 87 non-classic HH Portuguese patients. A total of 1241 genetic alterations were detected corresponding to 53 different variants, 13 of which were not described in the available public databases. Among them, five were predicted to be potentially pathogenic: three novel mutations in TFR2 [two missense (p.Leu750Pro and p.Ala777Val) and one intronic splicing mutation (c.967-1GNC)], one missense mutation in HFE (p.Tyr230Cys), and one mutation in the 5′-UTR of HAMP gene(c.-25GNA). The results reported here illustrate the usefulness of NGS for targeted iron metabolism-related gene panels, as a likely cost-effective approach for molecular genetics diagnosis of non-classic HH patients. Simultaneously, it has contributed to the knowledge of the pathophysiology of those rare iron metabolism-related disorders.