Elevation of serum thioredoxin levels in patients with nonalcoholic steatohepatitis.

Thioredoxin (TRX) is induced by many oxidative stresses. Serum TRX levels were significantly elevated in nonalcoholic steatohepatitis (NASH) patients, as compared to simple fatty liver (FL) patients or healthy controls. Serum TRX levels in NASH patients were significantly correlated with serum ferritin levels, but not with other variables. Removal of hepatic excess iron by phlebotomy significantly decreased the serum levels of TRX and ALT in NASH patient. Therefore, the pathogenesis of NASH may be associated with iron-related oxidative stress. The serum TRX level is a parameter for discriminating NASH from FL.     

Iron status in young Danish men and women: a population survey comprising 548 individuals

Iron status was assessed by measurement of serum (S-) ferritin and hemoglobin (Hb) in 548 randomly selected healthy Danes (264 men, 284 women) with a median age of 25 years (range 16–31). S-ferritin values in men displayed a gradual increase with age, and at all ages, men had higher values than women. Iron deficiency (i.e., S-ferritin < 16 g/l) was observed in 0.8%; none had iron deficiency anemia (i.e., S-ferritin <16g/l and Hb<129g/l). Daily iron supplementation was used by 15.5%. The frequency of iron deficiency was 0% in supplement users vs 0.9% in nonusers. The frequency of preclinical hereditary hemochromatosis was 0.38%. There was a slight insignificant increase in S-ferritin values of women with age. Iron deficiency was observed in 14.7% of 16- to 19-year-olds, in 9.2% of 20- to 24-year-olds, and in 8.6% of 25- to 31-year-old women (p<0.01), and iron deficiency anemia (i.e., S-ferritin <16g/l and Hb <121 g/l) in 14.7%, 3.4%, and 3.7%, respectively (p<0.01). Daily iron supplementation was used by 21.5%. The frequency of iron deficiency in users was 4.9% vs. 10.8% in nonusers, and the frequency of iron deficiency anemia 1.6% in users vs. 5.8% in nonusers. The results indicate a satisfactory iron status in young men. There is a high frequency of iron deficiency in young women, suggesting that preventive measures should be considered in this risk group.     

Sulfide silver amplification of ferritin iron cores in blood and bone marrow cells

Summary A short exposure of cell suspensions to gaseous hydrogen sulfide, appropriate fixations, and subsequent physical development of silver shells around sulfidated insoluble metals were used to amplify ferritin iron cores in blood and bone marrow cells. The methods described are suitable for both light microscopy and transmission electron microscopy. These techniques made it possible to visualize Prussian Blue stainable ferritin and haemosiderin, as well as a large variety of isoferritin iron and other smaller particles beyond the sensitivity of Prussian Blue staining. Admixtures of sulfidatible zinc and traces of other heavy metals had to be taken into consideration. For further research, adaptations of sulfide silver staining to microphysical analyses were developed. However, conventional energy dispersive X-ray analysis was not sensitive enough to signalize the presence of Fe in sulfide silver amplified iron cores of a single or a few ferritin molecule(s). Proton-induced X-ray emission was used to measure Fe and Zn down to 1 fg/single cell in unstained or sulfide silver stained smears on thin foils. However, multielement analysis of homogeneous cell concentrates was much easier to perform and far more sensitive. In advanced iron overload, highly increased sulfide silver staining was found in peripheral blood cells including lymphocytes, monocytes, eosinophils, basophils, and — in extreme cases — also in neutrophils and platelets.     

肾性贫血患者血清铁蛋白与叶酸检测的价值

目的探讨肾性贫血患者血清铁蛋白与叶酸检测的价值。方法抽样选取该院诊治的肾性贫血患者75例（观察组）,再选取同期健康志愿者75例（对照组）进行对比分析,分别于治疗前后对两组进行血清铁蛋白于与叶酸的检测。结果观察组患者在治疗前的血清铁蛋白与叶酸含量明显低于对照组,差异有统计学意义（P〈0.01）。但是治疗后,观察组患者的血清铁蛋白含量略低于对照组,差异无统计学意义（P〉0.05）;而叶酸含量,观察组却仍远低于对照组,差异有统计学意义（P〈0.05）。结论对于肾性贫血患者的血清铁蛋白、叶酸含量变化进行有效的掌握,为其具体的诊治极具指导意义。     

Labile iron,ROS, and cell death are prominently induced by haemin,but not by non-transferrin-bound iron

BackgroundIn transfusion-related iron overload, haem-derived iron accumulation in monocytes/macrophages is the initial event. When iron loading exceeds the ferritin storage capacity, iron is released into the plasma. When iron loading exceeds transferrin binding capacity, labile, non-transferrin-bound iron (NTBI) appears and causes organ injury. Haemin-induced cell death has already been investigated; however, whether NTBI induces cell death in monocytes/macrophages remains unclear.Material and MethodsHuman monocytic THP-1 cells were treated with haemin or NTBI, particularly ferric ammonium citrate (FAC) or ferrous ammonium sulfate (FAS). The intracellular labile iron pool (LIP) was measured using an iron-sensitive fluorescent probe. Ferritin expression was measured by western blotting.ResultsLIP was elevated after haemin treatment but not after FAC or FAS treatment. Reactive oxygen species (ROS) generation and cell death induction were remarkable after haemin treatment but not after FAC or FAS treatment. Ferritin expression was not different between the FAC and haemin treatments. The combination of an iron chelator and a ferroptosis inhibitor significantly augmented the suppression of haemin cytotoxicity (p = 0.011).DiscussionThe difference in LIP suggests the different iron traffic mechanisms for haem-derived iron and NTBI. The Combination of iron chelators and antioxidants is beneficial for iron overload therapy.     

Decreased levels of ferritin,mild thrombocytosis,and increased erythropoietin are sequential events among frequent plateletpheresis donors: Implication for a ferritin screen

BackgroundIt is generally recognized that repeat apheresis increases the risk for iron deficiency, thus may impact on the blood homeostasis. With regard to donor vigilance, we clarified the mid- to long-term effects of plateletapheresis by comparing the most frequent donors with the first-time ones in hematological and biochemical tests.MethodsLevels of erythropoietin (EPO), hemoglobin (Hb) and ferritin were analyzed in double-unit (500 mL whole blood or 6 × 10¹¹ apheresis platelets) donations in three male cohorts, with identifiers of first-time whole-blood donors (n = 30), first-time platelet donors transited from maximal whole blood to apheresis (n = 30) and frequent donors subjected to extreme plateletpheresis (n = 90), respectively. According to the number of donations, the last earnest cohort, who donate almost 24 times a year, was further subdivided into three groups– casual (76–120 life-time donations in 5 years), mediocre (121–168 within 7 years) and enthusiastic (≥169 within 7 years and a month).ResultsRegardless of the donation experience in whole blood or plateletpheresis, iron deficiency (serum ferritin concentrations <15 μg/L) was identified in all earnest cohorts. The ferritin means were significantly lower in plateletpheresis groups, with the lowest values in the enthusiastic group. EPO levels showed a significant inverse correlation with ferritin (p = 0.015, r = –0.224). Long-term earnest donors had the lowest iron stores accompanied by a later thrombocytosis and a final increase in EPO was revealed.ConclusionRegular ferritin screens are crucial to ensure a high level of donor health protection.     

Insights on Regulation and Function of the Iron Regulatory Protein 1 (IRP1)

Iron regulatory protein 1 (IRP1) controls the translation or stability of several mRNAs by binding to iron responsive elements (IREs) within their untranslated regions. Its activity is regulated by an unusual iron-sulfur cluster (ICS) switch. Thus, in iron-replete cells, IRP1 assembles a cubane [4Fe-4S] cluster that prevents RNA-binding activity and renders the protein to cytosolic aconitase. We show that wild type or mutant forms of IRP1 that fail to assemble a [4Fe-4S] cluster are sensitized for iron-dependent degradation by the ubiquitin-proteasome pathway. The regulation of IRP1 abundance poses an alternative mechanism to prevent accumulation of inappropriately high IRE-binding activity when the ICS assembly pathway is impaired. To study functional aspects of IRP1, we overexpressed wild type or mutant forms of the protein in human H1299 lung cancer cells in a tetracycline-inducible fashion, and analyzed how this affects cell growth. While the induction of IRP1 did not affect cell proliferation in culture, it dramatically reduced the capacity of the cells to form solid tumor xenografts in nude mice. These data provide a first link between IRP1 and cancer.     

Hematologic and vitamin status of african american women and their relationships to pregnancy outcome

A prospective observational study was conducted to investigate the effects of nutrition and related factors on the outcome of pregnancy in nulliparous African American women 16–35 years of age. Blood samples from a subset of these subjects were taken during the first (1st), second (2nd) and third (3rd) trimesters of pregnancy and at delivery. Cord blood samples were also collected at delivery. Levels of selected biochemical variables including serum ferritin, vitamin B₁₂ and folate as well as whole blood folate, and selected hematologic indices were determined and correlated with pregnancy outcome variables. During the second trimester of pregnancy, values for hematocrit and hemoglobin were less than 30% and 11 g/dL, respectively, in 16% and 30% of the participants, respectively. Serum and whole blood (WB) folate increased sequentially during pregnancy. Cord concentrations of serum folate were significantly higher than maternal concentrations at delivery (P<0.05). Serum ferritin declined significantly from 36±5.6 ng/ml in the first trimester to 17±1.5 ng/ml during the 3rd trimester (P<0.05), and returned to the 2nd trimester level (26±2.0 ng/ml) at delivery. Second trimester WB folate was positively related to birth weight (R²=0.21), while gestational age was inversely correlated with 3rd trimester vitamin B₁₂ (R²=0.34). These data suggest that vitamin B₁₂ and folate play an important role in the outcome of pregnancy in this population.     

Alcohol Induction of Ferritin Expression in a Human Hepatoblastoma Cell Line (HEP G2)

Hyperferritinemia, an unclear mechanism, is frequently observed in chronic alcoholics. The aim of this work was to study the effect of alcohol on ferritin expression in a human hepatoblastoma cell line, HepG2. This cell line proved to be sensitive to alcohol, since alcohol increased gamma-GT activity both in cells and media. The most striking result was the increase of ferritin in cells and media by alcohol. Moreover, this effect was specific, since it contrasted with a decrease in total protein synthesis and secretion, a decrease in transferrin excretion and a lack of effect on orosomucoid. In our model, alcohol was able to induce, in a specific manner, ferritin expression.