继发铁过载研究进展

继发铁过载多发生于输血依赖的患者,过量的铁沉积在重要器官,会对患者生存产生显著的影响.单纯依靠血清铁蛋白不能客观反映特定器官铁的沉积.评价体内铁过载的无创性方法主要有超导量子干涉仪和磁共振T2*.输血依赖的患者应定期监测体内铁过载的情况,并及时进行祛铁治疗.目前临床使用的祛铁剂主要有祛铁胺、祛铁酮和 Deferasimx.     

铁过载检测在骨质疏松症诊断中的作用

绝经后女性体内铁含量较绝经前升高,铁过载与骨质疏松有明显关系。了解体内铁过载状况在骨质疏松防治中具有积极价值。检测体内铁水平的方法较多,目前尚无统一标准,文献报道亦不一。本文对目前临床及实验室采用的铁过载检测方法进行比较与综述,以期为骨质疏松防治中检测铁过载提供相关参考。     

MRI评价肝脏铁过载的应用进展

许多研究表明,肝脏铁过载与肝炎、肝纤维化、肝硬化及肿瘤具有密切关系.目前检测铁过载的方法,如血浆铁蛋白检测、肝脏穿刺活检以及无创检查超导量子干涉仪等均具有一定的局限性,磁共振检查技术(magneticresonanceimaging,MRI)是目前公认的,能够无创、安全、准确的检查肝脏铁含量的方法.本文对肝脏铁过载及MRI在肝脏铁过载中的应用进展进行综述.     

铁过载对器官功能损伤及磁共振检测铁过载研究进展

铁过载可导致多器官功能损害。铁过载的病情隐匿,表现多样,进展缓慢,组织受累程度多变,常在组织和器官显著受损后才能作出诊断。及时进行铁螯合治疗能有效减轻损害程度。因此,及时检测器官铁过载至关重要。目前检测铁含量的指标包括肝活检检测肝铁浓度(liver iron concentration,LIC)、血清铁蛋白(serum ferritin,SF)和转铁蛋白饱和度(transferrin saturation,TS)及核磁共振成像(MRI)。由于MRI检测器官的无创性及可靠性,该技术越来越受到学者的重视。本文就铁过载引起各个器官的损害情况及MRI检测器官铁过载的结果做一综述。     

铁过载及铁死亡与代谢相关脂肪性肝病的研究进展

铁作为机体必须的微量元素,对维持机体健康至关重要。过多的铁离子可促进活性氧的产生,从而对细胞、组织造成损伤。随着铁死亡这一铁依赖性的细胞死亡方式概念的提出,越来越多的研究聚焦到铁死亡。近年来的研究证实了铁过载及铁死亡与代谢性疾病之间的关系,为代谢相关脂肪性肝病等疾病的防治带来了曙光。该文就国内外铁过载及铁死亡与代谢相关...     

酒精性肝病患者血清铁蛋白和血清铁检测的意义

目的探讨检测血清铁和血清铁蛋白水平对诊断酒精性肝病（ALD）患者的意义。方法在61例慢性乙型肝炎（CHB）、34例CHB合并ALD、75例ALD和30例正常人,采用放射免疫法检测血清铁蛋白;使用全自动生化分析仪测定血清铁;采用微粒子发光法检测血清乙型肝炎病毒标记物。结果 CHB/ALD和ALD患者血清铁分别为8.04±4.38μmol/L和9.41±3.59μmol/L,血清铁蛋白水平分别为267.54±42.12μg/L和276.16±61.14μg/L,与CHB和正常人比,差异显著（P〈0.05）;酒精性肝炎和肝硬化患者血清铁和铁蛋白水平与酒精性脂肪肝患者比,差异也有显著性意义（P〈0.001）。结论 ALD患者存在明显的铁代谢异常。     

肝病患者血清铁蛋白水平与肝脏炎症程度及肝病类型的关系

目的分析血清铁蛋白(SF)水平与肝病类型及肝脏炎症程度的关系。方法选取203例入院时SF升高的急慢性肝病患者,采用全自动生化分析仪检测患者清晨空腹血清丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、白蛋白(ALB),同时采用免疫比浊法检测SF、络合法测定血清铁(SI),分析SF、SI与肝功能炎症指标相关性,及SF、SI在不同类型肝病、不同程度肝脏炎症患者中的变化特点。结果 SF、SI与ALT、AST均呈正相关(P均<0.01),SF与ALB呈负相关(P<0.01)。SF水平在戊型肝炎、药物性肝炎、乙型肝炎、丙型肝炎患者中依次升高(χ2=13.551,P<0.01),ALT、AST的升高程度同SF一致;SI在不同类型肝病患者之间的差异无统计学意义(P>0.05)。SF在急性肝炎与肝衰竭中的升高水平较慢性肝炎、肝硬化、肝癌患者明显;SI在肝癌患者表达量最低,其余四组之间的差异无统计学意义(P>0.05)。结论 SF与肝脏炎症程度正相关,在丙肝及肝衰竭患者中,SF比ALT、AST更能反映患者的病情。     

铁过载对成骨细胞铁稳态及生物活性的影响

目的了解铁过载对成骨细胞铁稳态及生物活性的影响。方法 34℃条件下体外培养人成骨细胞(hFOB1.19),以不同浓度(50、100、200μmol/L)枸橼酸铁铵(FAC)干预,用RT-PCR检测成骨细胞铁调节基因膜转铁蛋白(FPN1)、转铁蛋白受体(TfR)和二价金属转运蛋白1(DMT1)表达的变化;用激光共聚焦扫描显微镜(CLSM)观察成骨细胞铁离子荧光强度;流式细胞仪检测成骨细胞活性氧(ROS)水平;碱性磷酸酶活性试剂盒检测碱性磷酸酶活性;Vonkossa染色法行钙结节染色。结果与对照组相比,FAC干预48h后FPN1mRNA的表达随FAC干预浓度增加呈剂量依赖性上调,TfR、DMT1mRNA的表达呈剂量依赖性下调(P0.05);FAC干预48h后成骨细胞铁离子荧光强度剂量依赖性减弱,与对照组相比差异有统计学意义(P0.05);48h后成骨细胞ROS水平随FAC干预浓度增加呈剂量依赖性升高(P0.05);FAC干预10d后各组成骨细胞碱性磷酸酶活性均随FAC浓度增高而降低,差异有统计学意义(P0.05);与对照组相比,FAC干预17d后成骨细胞钙结节染色显示矿化面积和钙结节形成随FAC浓度增加而减少。结论铁过载对成骨细胞生物活性有明显抑制作用,其机制可能与细胞内铁离子浓度增加及活性氧水平升高有关。     

Iron overload and iron chelation therapy in thalassaemia and sickle cell haemoglobinopathies

This paper reviews the factors governing the rate of iron loading and iron toxicity in the thalassaemia syndromes and sickle cell disease. It outlines the main determinants of iron mobilization by the iron-chelating drug, desferrioxamine, together with the effects of this drug in clinical practice.     

Iron chelation therapy for transfusional iron overload: a swift evolution

Chronic transfusional iron overload leads to significant morbidity and mortality. While deferoxamine (DFO) is an effective iron chelator with over four decades of experience, it requires tedious subcutaneous infusions that reflect negatively on patient compliance. The novel oral iron chelators deferiprone (L1) and deferasirox (DFRA) opened new horizons for the management of transfusional siderosis. A large body of evidence is now available regarding their efficacy and safety in various populations and settings. Nevertheless, experience with both drugs witnessed some drawbacks, and the search for an ideal and cost-effective iron chelator continues.     

Iron overload and tuberculosis: a case for iron chelation therapy.

Elevated levels of iron impair immune defence mechanisms, and specifically the macrophage function of innate immunity. Iron enhances Mycobacterium tuberculosis infection, M. tuberculosis replication, progression to clinical disease and death from tuberculosis (TB). Chelation of iron in individuals with an excessive iron burden may reduce M. tuberculosis viability and replication, restore host defence mechanisms and could find application in the prevention and treatment strategies in settings where both iron overload and TB are prevalent. The objective of this paper was to summarise recent literature on the role of iron in TB pathogenesis and to examine the potential of iron chelation therapy. The literature confirms a key role for iron in mycobacterial virulence. The ability of chelation to enhance host effector mechanisms and to inhibit replication of various pathogens justifies further studies into iron chelation as a potential additive therapy for TB.     

Long-term efficacy of deferoxamine iron chelation therapy in adults with acquired transfusional iron overload

Transfusional iron overload in adult patients with acquired anemias may result in widespread organ dysfunction. Long-term deferoxamine mesylate therapy was administered by continuous subcutaneous infusion to six such patients, who have been followed up for up to 66 months of therapy while continuing to be transfusion-dependent. During deferoxamine therapy, liver density by computed tomographic scan decreased in four of five patients, liver iron content decreased in two of three patients, and liver function normalized in two patients. Plasma cortisol response to insulin-induced hypoglycemia improved in three of five patients receiving therapy. Pituitary growth hormone reserve normalized in two patients and remained normal in the other three tested. One patient, treated concurrently with ascorbic acid, died suddenly. The other five patients have had no cardiac deterioration by noninvasive testing. We conclude that long-term deferoxamine iron chelation therapy is effective not only in retarding but, in some cases, even reversing organ damage caused by transfusional iron overload.     

Cardiac function during iron chelation therapy in adult non-thalassaemic patients with transfusional iron overload

Abstract: It is well-documented that iron chelation by desferrioxamine protects/improves the cardiac function in blood transfusion-dependent children suffering from ß-thalassaemia. In patients who do not become dependent upon blood transfusion until adulthood (ANT-patients), iron chelation by desferrioxamine may affect the cardiac function in unknown ways, presumably because age-related changes in the heart may cause iron chelation to affect the cardiac function in different ways. We therefore followed the left ventricular ejection fraction (LVEF) by multigated radionuclide angiography in 16 iron-loaded ANT-patients during iron chelation alone and after increasing the efficacy of chelation by vitamin C supplementation. During 12 months of iron chelation the mean LVEF fell significantly from 63.3% to 58.0% (p = 0.04). Individual changes in LVEF did not correlate significantly with age but with the pretreatment liver iron concentration. After initiation of vitamin C supplementation, the mean LVEF increased from 55.9% to 65.3% (p = 0.01). Our data suggest that in ANT-patients prolonged desferrioxamine treatment without vitamin C supplementation may be associated with reduced LVEF, whereas vitamin C supplementation seems to benefit the cardiac function. Similar findings have not been described in ß-thalassaemia and may hence be specific for ANT-patients. However, our findings have to be confirmed by controlled studies.     

Successful reversal by chelation therapy of congestive cardiomyopathy due to iron overload

A patient who developed severe iron overload cardiomyopathy is described. Venesection could not be performed because the patient had chronic anemia. Deferoxamine mesylate, a chelating agent, was administered daily for more than 2 years and produced significant improvement in ventricular function which was associated with a biopsy-proven decrease in myocardial iron stores. This is the first reported case in which a severe cardiomyopathy due to iron overload was reversed by chelation therapy alone.     

Overview of guidelines on iron chelation therapy in patients with myelodysplastic syndromes and transfusional iron overload

Between 2002 and 2008, a number of consensus statements and guidelines were developed by various groups around the world to educate healthcare professionals on the treatment of myelodysplastic syndromes (MDS), including the management of transfusional iron overload with iron chelation therapy. Guidelines have been developed by The Italian Society of Hematology, The UK MDS Guidelines Group, The Nagasaki Group, The National Comprehensive Cancer Network, and The MDS Foundation. These guidelines show that the approaches to managing iron overload in patients with MDS are region specific, differing in their recommendations for when iron chelation therapy should be initiated and strategies for the ongoing management of iron overload. The guidelines all agree that red blood cell transfusions are clinically beneficial to treat the symptomatic anemia in MDS, and that patients with low-risk MDS receiving transfusions are the most likely to benefit from iron chelation therapy.