The plasma59Fe clearance curve in man

Summary Studies of⁵⁹Fe clearance from the plasma are used for obtaining a quantitative measure of erythropoiesis. However, there are many difficulties associated with a good definition and a valid analysis of the plasma⁵⁹Fe clearance curve. The low plasma activity, plasma iron variation, and traces of haemolysis are factors which make the measurement of the curve difficult. All these problems were examined in the present work. Liquid scintillation counting allows a more accurate assay of plasma⁵⁹Fe activity than conventional gamma counting. Plasma iron fluctuations may affect tracer kinetics but adjustment of plasma activity for plasma iron variation (expressing⁵⁹Fe activity per unit mass of iron) does not appear a satisfactory procedure for overcoming this difficulty. The removal of haemoglobin from plasma samples is a necessary procedure to avoid contamination by [⁵⁹Fe] haemoglobin. Fitting three exponentials to the plasma⁵⁹Fe clearance curve does not yield satisfactory results in some cases. A better prediction of the clearance curve in most cases can be obtained by means of a more refined mathematical model.The research was supported by C.N.R. Contract No. 78.00513.86 within the Special Project on Biomedical Engineering.     

Intranasal deferoxamine reverses iron-induced memory deficits and inhibits amyloidogenic APP processing in a transgenic mouse model of Alzheimer's disease

Increasing evidence indicates that a disturbance of normal iron homeostasis and an amyloid-β (Aβ)-iron interaction may contribute to the pathology of Alzheimer's disease (AD), whereas iron chelation could be an effective therapeutic intervention. In the present study, transgenic mice expressing amyloid precursor protein (APP) and presenilin 1 and watered with high-dose iron served as a model of AD. We evaluated the effects of intranasal administration of the high-affinity iron chelator deferoxamine (DFO) on Aβ neuropathology and spatial learning and memory deficits created in this AD model. The effects of Fe, DFO, and combined treatments were also evaluated in vitro using SHSY-5Y cells overexpressing the human APP Swedish mutation. In vivo, no significant differences in the brain concentrations of iron, copper, or zinc were found among the treatment groups. We found that high-dose iron (deionized water containing 10 mg/mL FeCl₃) administered to transgenic mice increased protein expression and phosphorylation of APP695, enhanced amyloidogenic APP cleavage and Aβ deposition, and impaired spatial learning and memory. Chelation of iron via intranasal administration of DFO (200 mg/kg once every other day for 90 days) inhibited iron-induced amyloidogenic APP processing and reversed behavioral alterations. DFO treatment reduced the expression and phosphorylation of APP protein by shifting the processing of APP to the nonamyloidogenic pathway, and the reduction was accompanied by attenuating the Aβ burden, and then significantly promoted memory retention in APP/PS1 mice. The effects of DFO on iron-induced amyloidogenic APP cleavage were further confirmed in vitro. Collectively, the present data suggest that intranasal DFO treatment may be useful in AD, and amelioration of iron homeostasis is a potential strategy for prevention and treatment of this disease.     

铁代谢对于β地中海贫血表型的修饰作用的研究进展

β地中海贫血(简称地贫)是由于β珠蛋白基因缺陷导致β珠蛋白肽链合成减少的遗传性溶血性疾病。其病理机制为α/β珠蛋白肽链比例严重失衡,多余的α珠蛋白链沉积形成包涵体,引发红细胞溶血、无效造血以及继发性多组织器官铁超载等。机体铁负荷过重可能导致生长发育停滞、肝硬化、心功能不全等并发症,加重其表型。近年来,随着机体铁代谢相关基因相继被发现,铁代谢在地贫的发生发展过程中的机理逐渐被阐明。研究人员通过改变铁调素、转铁蛋白受体等铁代谢关键基因的表达,揭示了限制红细胞铁应用可改善β地贫无效造血和铁过载的症状,为治疗地贫提供了一个新的途径。本文围绕铁代谢相关基因以及通路在β地贫中的研究进展进行综述。     

Iron homeostasis in arthropathies: From pathogenesis to therapeutic potential

Iron is an essential element for proper functioning of cells within mammalian organ systems; in particular, iron homeostasis is critical for joint health. Excess iron can induce oxidative stress damage, associated with the pathogenesis of iron-storage and ageing-related diseases. Therefore, iron levels in body tissues and cells must be tightly regulated. In the past decades, excess iron content within joints has been found in some patients with joint diseases including hemophilic arthropathy, hemochromatosis arthropathy, and osteoarthritis (OA). Currently, increased evidence has shown that iron accumulation is closely associated with multiple pathological changes of these arthropathies. This review summarizes system-level and intracellular regulation of iron homeostasis, and emphasizes the role of iron in synovial alterations, cartilage degeneration, and subchondral bone of several arthropathies. Of note, we discuss the potential link between iron homeostasis and OA pathogenesis. Finally, we discuss the therapeutic potential of maintaining iron homeostasis in these arthropathies.     

Hepatic Steatosis Is Associated with Elevated Serum Iron in Patients with Obesity and Improves after Laparoscopic Sleeve Gastrectomy

BackgroundIron is closely related to metabolism. However, the relationship between iron and hepatic steatosis has not been fully elucidated.ObjectiveWe aimed to investigate the triangular relationship between iron and hepatic steatosis and laparoscopic sleeve gastrectomy (LSG) in patients with obesity.MethodsA total of 297 patients with obesity and 43 healthy individuals with a normal BMI were enrolled. Eighty-two patients underwent LSG. Anthropometrics, glucose-lipid metabolic markers, and hepatic steatosis assessed by FibroScan (CAP value and E value) were measured at baseline, and again at follow-up time intervals of 6 months and 1 year after surgery.Results(1) Iron was significantly higher in patients with obesity or overweight than in the individuals with normal BMI (8.18 ± 1.47 vs. 7.46 ± 0.99 mmol/L, p = 0.002). Iron was also higher in subjects with high blood pressure, dyslipidemia, and hyperuricemia than non-corresponding disorders (all p < 0.05). Moreover, iron was significantly higher in the severe than mild or moderate non-alcoholic fatty liver disease (NAFLD) group (p = 0.046 and 0.018). (2) Iron was positively associated with body weight, BMI, waist-to-hip ratio, uric acid, liver enzymes, postprandial blood glucose, fasting insulin, HOMA-IR, triglycerides, free fatty acid, and hepatic steatosis (CAP value), and negatively associated with high-density lipoprotein cholesterol (all p < 0.05). Iron was also positively associated with the visceral adipose area in patients with obesity and negatively associated with the subcutaneous adipose area in patients with overweight (all p < 0.05). (3) Iron levels and CAP values were decreased gradually 6 months and 1 year after surgery (all p < 0.05).ConclusionsOverall, our results indicated that iron is associated with hepatic steatosis in obesity. The iron level was significantly higher in patients with severe NAFLD than with mild or moderate NAFLD. LSG may reduce iron levels while improving fat deposition in the liver.     

Hematologic Recovery after Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation in Children with High-Risk Solid Tumors

Although the number of studies using tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) for the treatment of high-risk pediatric solid tumors has been increasing, documentation of hematologic recovery after tandem HDCT/autoSCT is very limited. For this reason, we retrospectively analyzed the hematologic recovery of 236 children with high-risk solid tumors who underwent tandem HDCT/autoSCT. The median numbers of CD34⁺ cells transplanted during the first and second HDCT/autoSCT were 4.3 × 10⁶/kg (range 0.6-220.2) and 4.1 × 10⁶/kg (range 0.9-157.6), respectively (P = 0.664). While there was no difference in neutrophil recovery between the first and second HDCT/autoSCT, platelet and RBC recoveries were significantly delayed in the second HDCT/autoSCT (P < 0.001 and P < 0.001, respectively). Delayed recovery in the second HDCT/autoSCT was more prominent when the number of transplanted CD34⁺ cells was lower, especially if it was < 2 × 10⁶/kg. A lower CD34⁺ cell count was also associated with increased RBC transfusion requirements and a higher serum ferritin level after tandem HDCT/autoSCT. More CD34⁺ cells need to be transplanted during the second HDCT/autoSCT in order to achieve the same hematologic recovery as the first HDCT/autoSCT.     

The Physiological Role of Ferritin-Like Compounds in Bacteria

Iron, as the ferrous or ferric ion, is essential for the life processes of all eukaryotes and most prokaryotes; however, the element is toxic when in excess of that needed for cellular homeostasis. Ferrous ions can react with metabolically generated hydrogen peroxide to yield toxic hydroxyl radicals that in turn degrade lipids, DNA, and other cellular biomolecules. Mechanisms have evolved in living systems for iron detoxification and for the removal of excess ferrous ions from the cytosol. These detoxification mechanisms involve the oxidation of excess ferrous ions to the ferric state and storage of the ferric ions in ferritin-like proteins.

There are at least three types of ferritin-like proteins in bacteria: bacterial ferritin, bacterioferritin, and dodecameric ferritin. These bacterial proteins are related to the ferritins found in eukaryotes. The structure and physical characteristics of the ferritin-like compounds have been elucidated in several bacteria. Unfortunately, the physiological roles of the bacterial ferritin-like compounds have been less thoroughly studied. A few studies conducted with mutants indicated that ferritin-like compounds can protect bacterial cells from iron overload, serve as an iron source when iron is limited, protect the bacterial cells against oxidative stress and/or protect DNA against enzymatic or oxidative attack. There is very little information available concerning the roles that ferritin-like compounds might play in the survival of bacteria in food, water, soil, or eukaryotic host environments.     

磁敏感加权成像脑铁含量感兴趣区选择及测量研究

目的探讨苍白球区异常矿物质沉积时,选取不同感兴趣区(region of interest,ROI)(整个苍白球或局部矿物质沉积区域)对铁含量测值的影响,从而为脑组织铁含量测定感兴趣区选择及其测量的便捷性提供依据。材料与方法采用常规磁共振成像和磁敏感加权成像扫描94例健康志愿者,其中苍白球区存在明显矿物质沉积10例,分别选取苍白球整体(A1组)及局部矿物质沉积区域(A2组)为ROI测量灰度值。另外选取性别和年龄相匹配的苍白球区无异常铁含量沉积10例作为对照组(B组)。通过Pearson线性相关分析比较苍白球区有无异常铁含量沉积时的信号值对苍白球区铁含量测量的影响。结果 A1组和A2组灰度值测量相关系数r=0.827(P0.05),整个苍白球区灰度值测量与局部区域灰度值测量具有显著一致性;A1组和B组相关系数r=0.183(P0.05),A2组和B组间相关系数r=0.344(P0.05),说明苍白球区内有无矿物质沉积对灰度值测量影响具有统计学意义。结论通过SWI技术分析含有异常矿物质沉积的苍白球区,选取整个苍白球区作为ROI与只将异常的矿物质沉积区作为ROI反映矿物质沉积趋势具有一致性,对脑铁测量影响不大,因此可以直接选取苍白球整体区域作为ROI测量脑铁含量,方法便捷,值得临床推广应用。