铁死亡与重大慢性疾病

铁死亡是近年发现的一种铁依赖的新型细胞死亡方式，其特征是脂质过氧化物和活性氧簇的过量蓄积。大量研究表明，铁死亡不仅在重大慢性疾病的发生发展过程中发挥重要作用，而且在不同的疾病背景下扮演不同角色。目前认为，铁死亡可抑制肿瘤生长并增加多种肿瘤对化疗药物和免疫治疗的敏感性，因此诱导铁死亡的发生拓展了肿瘤治疗思路。然而，在心脑血管疾病和神经退行性疾病中，铁死亡的发生通过引发正常组织器官损伤和功能丧失直接参与疾病的发生、发展及转归，因此针对心脑血管疾病和神经退行性疾病，抑制铁死亡的发生能够有效预防并延缓这些疾病的发生和发展。本文综述了铁死亡在恶性肿瘤、神经退行性疾病和心脑血管疾病三类不同重大慢性疾病中的最新研究进展及其潜在的作用机制，系统讨论了靶向铁死亡在防治重大慢性疾病中的临床应用前景，为重大慢性疾病的防治提供新的依据。     

基于倾向匹配法鉴别MCV和网织红细胞参数对地中海贫血和缺铁性贫血的价值

目的 探讨MCV(平均红细胞体积)和网织红细胞参数对地中海贫血和缺铁性贫血鉴别诊断的意义。方法回顾性收集2017年7月～2019年7月诊断为缺铁性贫血和地中海贫血的病例,依据诊断分为缺铁组(n=226)和地贫组(n=60)。采用倾向匹配法筛选基线资料,最终两组各纳入42例。比较两组MCV和网织红细胞参数。结果匹配后两组基线资料无显著性差异(P0.05),匹配前MCV两组间比较有差异(P0.05),匹配后没差异,匹配前后LFR/MFR/HFR(低荧光强度网织红细胞比率/中荧光强度网织红细胞比率/高荧光强度网织红细胞比率)在两组间比较均无差异(P0.05),Ret-He(网织红细胞血红蛋白)在匹配前后两组间比较,差异有统计学意义(P0.05)。结论 Ret-He对地中海贫血和缺铁性贫血鉴别诊断有一定的意义。     

Compliance and satisfaction with deferasirox (Exjade®) compared with deferoxamine in patients with transfusion-dependent beta-thalassemia

Objective

The current standard option for iron chelation therapy (ICT) in transfusion-dependent patients with beta-thalassemia is deferoxamine (DFO). We aimed to compare the compliance with DFO vs. deferasirox (Exjade^®), a novel oral iron chelator, in patients with transfusion-dependent beta-thalassemia.

Methods

In this cross-sectional study, 220 patients from Southern Iran who were receiving DFO or Exjade^® for the last 2 years were investigated in 2012. Satisfaction, compliance, convenience, and life disturbances of the patients with ICT were evaluated. Assessments were performed at four different occasions during 1 year.

Results

According to the results, 114 patients received treatment with DFO and 106 patients were treated with Exjade^®. In comparison with the patients who were treated with DFO, those receiving Exjade^® reported a significantly higher rate of compliance and convenience (P < 0.05). However, no significant difference was observed between the two groups regarding their satisfaction (P > 0.05). In the DFO group, 44.9% of the patients reported irritation and pain at the injection site.

Conclusions

Considering higher rate of compliance and convenience with Exjade^® and the comparable efficacy of these two modalities of ICT documented in previous studies, Exjade^® can be used as a preferable choice of ICT in iron-overload patients with beta-thalassemia.     

锌、铁、铜、镁4种元素在乙型肝炎肝硬化不同分期及中医证候中的分布研究

目的 初步探讨血清Zn、Fe、Cu、Mg 4种元素在乙型肝炎代偿期与失代偿期肝硬化中的含量情况以及其在不同中医证候间的分布差异。方法 选择符合诊断标准的乙型肝炎肝硬化患者95例,测定入组患者血清Zn、Fe、Cu、Mg的含量水平,收集中医四诊资料齐全者按照辨证标准进行分组,最后进行统计学分析。结果 血清Zn、Mg在乙型肝炎肝硬化失代偿期显著低于乙型肝炎肝硬化代偿期,肝气郁结证及湿热蕴结证为乙型肝炎肝硬化多发证侯,血清Zn在乙型肝炎肝硬化水湿内阻证组显著低于瘀血阻络证组（P〈0.05）。结论 血清Zn、Mg含量随着乙型肝炎肝硬化病变程度加重而降低,动态监测两者水平对于判断该病的病情轻重程度及转归具有一定指导意义,而血清Zn在乙型肝炎肝硬化不同中医证候间的分布存在一定的差异性。     

Aging is an organ-specific process: changes in homeostasis of iron and redox proteins in the rat

Organ-specific changes of iron- and redox-related proteins occur with age in the rat. Ferritin, the major iron storage and detoxifying protein, as well as the proteins of the methionine-centered redox cycle (MCRC) were examined in old and young animals, and showed organ-dependent changes. In spleens and livers of aged rats, ferritin (protein) levels were greater than in young ones, and their iron saturation increased, rendering higher ferritin-bound iron (FtBI). Iron saturation of the ferritin molecule in the tongues and sternohyoids of old rats was lower but ferritin level was higher than in young rats, resulting in increased FtBI with age. Ferritin level in the esophagus of older rats was lower than in young rats but its molecular iron content higher thus the total FtBI remained the same. In the larynx, both ferritin and its iron content were the same in young and old animals. MCRC proteins were measured in livers and spleens only. With aging, methionine sulfoxide reductase A and B (MsrA and MsrB) levels in livers and spleens decreased. Thioredoxin1 (Trx) and Trx-reductase1 were elevated in old spleens, but reduced in livers. Aged spleens showed reduced Msr isozyme activity; but in the liver, its activity increased. mRNA changes with age were monitored and found to be organ specific. These organ-specific changes could reflect the different challenges and the selective pathways of each organ and its resultant capacity to cope with aging.     

Restless legs syndrome in hemodialysis patients: an epidemiologic survey in Greece

BackgroundRestless legs syndrome (RLS) is a sensorimotor disorder characterized by an uncontrolled need to move extremities accompanied by unpleasant sensations, which frequently leads to sleep disturbances. In hemodialysis (HD) patients, the previously reported RLS prevalence varied enormously, between 6% and 60%. In our study, we investigated the RLS prevalence in HD patients for the first time in Greece.MethodsA continuous sample of HD patients was studied between January and September of 2010 in six dialysis units in Greece. RLS diagnosis was based on the essential clinical criteria of the International RLS Study Group (IRLSSG). The standardized incidence ratio (SIR) for RLS in HD patients was calculated in comparison to data from a recent survey of the general population in Greece.ResultsIn our study of 579 HD patients in Greece (236 women; mean age, 65 ± 13 years), the prevalence of RLS was elevated in comparison to the general population (26.6% vs 3.9%), with an SIR of 5.4 (95% confidence interval [CI], 4.6–6.3). In the fully adjusted model, the risk for RLS in HD patients was reduced in older age (odds ratio [OR], 0.98 [95% CI, 0.96–0.99]) and increased in women (OR, 1.60 [95% CI, 1.05–2.43]) in cases with elevated levels of β₂ microglobulin (OR, 1.15 [95% CI, 1.01–1.32]) and intact parathormone (iPTH) (OR, 1.30 [95% CI, 1.08–1.56]).ConclusionA high RLS prevalence was recorded in a large HD population in Greece, clearly suggesting the need for enhanced awareness of RLS in nephrology. The RLS risk was increased in women and in younger HD patients as well as in those with elevated β₂ microglobulin and iPTH levels.     

Beyond the cardiorenal anaemia syndrome: recognizing the role of iron deficiency

Growing awareness that heart failure, renal impairment, and anaemia are frequent co‐morbidities which can exacerbate one another in a vicious circle of clinical deterioration has led to the concept of the cardiorenal anaemia syndrome (CRAS). The role of iron deficiency within this complex interplay has been less well examined. Scrutiny of data from the recent FAIR‐HF trial raises a new hypothesis: is it time for ‘CRAS’ to be supplemented with new acronyms such as CRIDS (cardiorenal–iron deficiency syndrome) or even CRAIDS (cardiorenal–anaemia–iron deficiency syndrome)? Iron deficiency occurs frequently in heart failure patients with or without anaemia. It not only impairs oxygen transport through reduced erythropoiesis, but adversely affects oxidative metabolism, cellular energetics, and immune mechanisms, and the synthesis and degradation of complex molecules such as DNA. One large observational study in patients with heart failure found iron deficiency to be an independent predictor of death or urgent heart transplantation (hazard ratio 1.58, 95% confidence interval 1.14–2.17, P = 0.005). In the FAIR‐HF trial, i.v. iron therapy was associated with significant improvements in physical functioning in iron‐deficient patients with heart failure, even in non‐anaemic patients in whom haemoglobin levels did not change following i.v. iron administration. Key questions regarding the use of i.v. iron supplementation in the setting of heart failure merit exploration and could readily be answered by appropriately designed clinical trials. It is to be hoped that these important clinical trials are conducted, to permit a more subtle characterization of the patient's pathological condition and interventional requirements.     

铁调素干预成骨细胞(hFOB1.19)后细胞膜转铁蛋白1、铁离子、矿化及成骨基因变化研究

目的 探讨铁调素对成骨细胞铁代谢指标、骨代谢指标的影响和相互关系。方法 成骨细胞 （hFOB1.19）培养3d后,使用逆转录-聚合酶链反应（RT-PCR）检测成骨细胞（hFOB1.19）的膜转铁蛋白1 （ferroportin1,Fpn1）的表达;再用不同浓度的铁调素（25noml/L,50noml/L,100noml/L）干预培养 环境,对照组加相同体积双蒸水,干预20h,MTT法检测细胞增殖情况;激光共聚焦扫描显微镜（CLSM）检 测成骨细胞内铁离子荧光染色后荧光强度变化情况;Von Kossa染色检测成骨细胞矿化情况;RT-PCR检测 骨钙素（BGP）、I型胶原（COL1）、骨保护素（OPG）基因表达。结果 1、成骨细胞存在Fpn1表达;2、铁 调素对成骨细胞增殖无显著影响（P>0.05）;3、铁调素干预后,成骨细胞内铁离子含量增多,且与铁调 素干预存剂量依赖性关系（P<0.05）;4、铁调素干预后,成骨细胞矿化功能增强,且与铁调素干预存剂 量依赖性关系（P<0.05）;5、RT-PCR检测显示不同浓度铁调素干预后,各组COL1、OPG、BGP mRNA均有表 达;不同浓度组的COL1、OPG、BGP mRNA表达光密度比值不同,组间密度比值比较存在统计学意义 （P<0.05）,但铁调素在400nmol/L时抑制OPG的表达（P<0.05）。结论 成骨细胞存在铁调素作用的膜转 铁蛋白-1,所以铁调素干预成骨细胞培养环境后细胞内铁离子发生特异性变化,同时细胞矿化指标显著增 加、细胞COL1、OPG、BGP mRNA表达含量增加;研究提示：铁调素可能通过膜转铁蛋白影响成骨细胞铁离 子变化,细胞铁代谢变化可能引起细胞成骨指标上调改变。     

Wound healing by topical application of antioxidant iron chelators: kojic acid and deferiprone

Kojic acid and deferiprone are iron chelators used for skin lightening and iron‐overload treatment, respectively. As iron chelation and free radical scavenging are principal factors for wound healing, it was hypothesised that the local application of these compounds might accelerate wound healing in rats. Ointments of 3%, 6% and 9% of deferiprone and kojic acid were prepared and topical treatment was performed on in vivo wound models for 12 days twice in day for test and control groups. Topical treatment with 3%, 6% and 9% showed significant improvement in wound healing after 4 days (P < 0·001). Topical application of 3% and 6% deferiprone enhanced wound healing after 8 days (P < 0·026 and P < 0·001, respectively). Accelerated wound healing was seen using 3% and 6% deferiprone after 12 days (P = 0·003 and P < 0·001, respectively). DPPH scavenging assay was also performed to compare the antioxidant potencies of kojic acid and deferiprone. Deferiprone had more free radical scavenging power than kojic acid. Generally, deferiprone topical treatment, accelerated wound healing more than kojic acid because of its higher antioxidant and iron chelation abilities.