正常人血清Hepcidin水平及与铁代谢指标的相关性分析

目的分析正常人血清Hepcidin水平及与铁代谢指标的关系。方法测定24例正常人血清Hepcidin及血清铁、铁蛋白、转铁蛋白、总铁结合力、转铁蛋白饱和度、可溶性转铁蛋白受体1和血红蛋白水平,采用相关分析及多元线性逐步回归分析分析Hepcidin与各参数间的相关性。结果本组正常人血清Hepcidin水平18．6（16．0,25．1）μg／L,不同性别Hepcidin水平差异无统计学意义（P〉0．05）;Hepcidin水平与铁蛋白呈正相关（r=0．723,P=0．000）,与转铁蛋白（r=-0．612,P=0．001）、总铁结合力（r=-0．646,P=0．001）、可溶性转铁蛋白受体1-铁蛋白指数（r=-0．566,P=0．004）呈负相关;多元线性逐步回归分析显示,转铁蛋白和血清铁浓度可作为Hepcidin的预测因子。结论健康成人Hepcidin水平与铁蛋白、转铁蛋白、总铁结合力等指标相关,转铁蛋白和血清铁浓度可作为Hepcidin水平的预测因子。     

Increased levels of serum transferrin receptor and serum transferrin receptor/log ferritin ratios in men with prostate cancer and the implications for body-iron stores

The serum transferrin receptor (sTfR) is a sensitive indicator of iron-deficiency erythropoiesis that is not affected by inflammation. Concentrations of this molecule are inversely correlated with body-iron stores, and increased body-iron stores are associated with an increased risk of cancer of the liver and lungs. However, an association between iron status as assessed on the basis of sTfR and prostate cancer has not been previously investigated. We measured sTfR and serum ferritin by means of an enzyme immunoassay in 27 men with newly diagnosed, untreated prostate cancer and in 72 controls. Our study population ranged in age from 38 to 78 years. The mean serum ferritin concentration in men with prostate cancer was 44.8% lower than that in men without this tumor ( P < .05). In contrast, the mean values of sTfR and sTfR/log serum ferritin were 32% and 60% higher, respectively, in men with prostate cancer than in those without this tumor ( P < .05). Differences between groups persisted after we took into account inflammation (alpha 1-acid glycoprotein > 1 g/L, C-reactive protein > 10 mg/L; P < .05). Among the entire study population and among men without inflammation, a higher percentage of subjects (29%-31%) than of controls (14%-22%) had sTfR values greater than 8 mg/L, suggestive of iron-deficiency erythropoiesis ( P < .05). The odds ratios for men with prostate cancer to have sTfR values of less than 2.9 mg/L (suggestive of increased body-iron stores) was 0, compared with 1.745 to 3.65 for the same men to have sTfR values greater than 8 mg/L. sTfR was negatively correlated with log ferritin ( r = -.422, P < .05) but did not correlate with tissue inflammation, tumor stage, or acute-phase proteins. It appears that prostate cancer is not associated with increased body-iron stores.     

Isoelectric focusing (IEF) and immunofixation for determination of disialotransferrin

Objectives: A new simplified method for detection and quantitation of disialontransferrin in serum is described.

Design and Methods: The method is based on polyacrylamide gel isoelectric focusing, direct immunofixation with a specific antibody, and measurement by computerized scanning densitometry. Disialotransferrin levels were determined in 24 teetotallers and 34 alcoholics at 3 moments during detoxification. Three groups of drinkers were arranged: group 1 (without), group 2 (with light), and group 3 (with severe hepatitis).

Results: The metho showed very good reproducibility and accuracy with a coefficient of variation between 5 to 8%. Alcoholic patients could be clearly separated from teetotallers, with a specificity of 100% and a sensitivity of 94%. After 12 days of alcohol withdrawal, disialotransferrin values declined in alcoholics but remained slightly high. They were not influenced by the severity of liver disease. No significant difference was found between the 3 groups.

Conclusions: An easy-to-perform, sensitive, and inexpensive method has been developed to quantify disialotransferrin that can be used by laboratories almost everywhere.     

肿瘤坏死因子α和干扰素γ对癌性贫血患者红细胞生成素生成和红系增生的影响

目的探讨癌性贫血患者EPO生成及红系增生的变化，以及TNF、IFN等负调控细胞因子对EPO生成及红系增生的影响。方法对50例癌性贫血患者、15例癌症无贫血患者及对照组采用放射免疫法检测血清EPO水平，ELISA方法检测血清可溶性转铁蛋白受体（sTfR）、TNF-α、IFN-γ水平，用直线回归方法及相关分析定量分析体内EPO生成、红系增生情况及其与TNF-α、IFN-γ的关系。结果癌性贫血患者血清EPO水平为（23．11±10．00）IU／L，明显低于同等程度贫血的缺铁性贫血患者的（43．00±22．00）IU／L（P〈0．01）；实测值／预估值（O／P）EPO为0．88（0．54～1．10），明显低于对照组及癌症无贫血患者，后二者之间的O／PEPO差异无统计学意义。癌性贫血患者的血清sTfR水平（30．8±16．95）nmol／L，高于健康对照组的（17．82±6．76）nmol／L，而低于溶血性贫血患者的（65．75±29．12）nmol／L，差异均有统计学意义（P〈0．05）；O／PsTfR为0．89（0．57～1．22），明显低于对照组及癌症无贫血患者，后二者之间O／PsTfR差异无统计学意义。正常情况下存在于log（EPO）与血红蛋白浓度之间以及log（sTfR）与血红蛋白浓度之间的反比关系消失。癌性贫血患者血清TNF-α、IFN-γ水平分别为（25．75±26．71）ng／L、（50．49±42．12）ng／L，均显著高于正常对照组及癌症无贫血组。TNF-α、IFN-γ水平与血红蛋白浓度之间呈负相关关系。TNF-α与O／PEPO、O／PsTfR之间呈负相关。血清IFN-γ水平与O／PEPO之间无相关关系，与O／PsTfR呈负相关。结论TNF-α、IFN-γ等负调控因子的作用下，内源性EPO对贫血的反馈性增生相对不足，以及骨髓红系对EPO的反应性增生相对不足参与癌性贫血的发病机制。     

免疫细胞化学法检测大鼠骨髓细胞转铁蛋白受体的建立及应用

目的 建立检测大鼠骨髓细胞转铁蛋白受体(TfR)的免疫细胞化学法,应用于大鼠慢性病贫血动物模型。方法 免疫细胞化学法(S-P)系统。结果 慢性病贫血组TfR表达总积分为68.6分,较正常对照组(144.8分)明显降低,抑制剂组为101.2分,介于正常组与炎症组之间,经单因素方差分析P<0.01。结论 该法简明、方便、特异性强,准确地反映了骨髓细胞TfR表达的程度。     

尿免疫球蛋白转铁蛋白α1-微球蛋白与尿肌酐比值参考区间的建立与评价

目的建立重庆地区健康成人尿免疫球蛋白（尿Ig）、尿转铁蛋白（TRF）、尿α1-微球蛋白（α1-M）与尿肌酐（Cr）比值的参考区间,并进行评价。方法从健康体检者筛选符合条件的受试者135例,测定尿Ig、尿TRF、α1-M、cr值,并计算尿Ig、尿TRF、α1-M与尿Cr比值的参考区间;并对42例确诊为肾病患者和42例无肾病对照的尿Ig、尿TRF、α1-M与尿Cr比值的结果进行评价。结果建立的重庆地区尿Ig、尿TRF、α1-M与尿Cr比值参考区间分别是：尿Ig／Cr为14．1～130．8mg／g;尿TRF／Cr为9．72～81．3mg／g;尿α1-M／Cr为23．0～280．2mg／g。与单纯的随机尿相比较,其明显提高特异性和正确度。结论建立了重庆市主城区尿Ig、尿TRF、尿α1-M与尿Cr的比值的参考区间,该参考区间能用于临床肾功能损害的评价。     

Transferrin/transferrin receptor-mediated drug delivery

Since transferrin was discovered more than half a century ago, a considerable effort has been made towards understanding tranferrin-mediated iron uptake. However, it was not until recently with the identification and characterization of several new genes related to iron homeostasis, such as the hemochromatosis protein HFE and the iron transporter DMT1, that our knowledge has been advanced dramatically. A major pathway for cellular iron uptake is through internalization of the complex of iron-bound transferrin and the transferrin receptor, which is negatively modulated by HFE, a protein related to hereditary hemochromatosis. Iron is released from transferrin as the result of the acidic pH in endosome and then is transported to the cytosol by DMT1. The iron is then utilized as a cofactor by heme and ribonucleotide reductase or stored in ferritin. Apart from iron, many other metal ions of therapeutic and diagnostic interests can also bind to transferrin at the iron sites and their transferrin complexes can be recognized by many cells. Therefore, transferrin has been thought as a "delivery system" for many beneficial and harmful metal ions into the cells. Transferrin has also be widely applied as a targeting ligand in the active targeting of anticancer agents, proteins, and genes to primary proliferating malignant cells that overexpress transferrin receptors. This is achieved by conjugation of transferrin with drugs, proteins, hybride systems with marcomolecules and as liposomal-coated systems. Conjugates of anticancer drugs with transferrin can significantly improve the selectivity and toxicity and overcome drug resistance, thereby leading to a better treatment. The coupling of DNA to transferrin via a polycation such as polylysine or via cationic liposomes can target and transfer of the extrogenous DNA particularly into proliferating cells through receptor-mediated endocytosis. These kinds of non-viral vectors are potential alternatives to viral vectors for gene therapy, if the transfection efficiency can be improved. Moreover, transferrin receptors have shown potentials in delivery of therapeutic drugs or genes into the brain across blood-brain barrier.     

慢性肾脏病晚期肾性贫血患者可溶性转铁蛋白受体水平变化及意义

目的探讨血清可溶性转铁蛋白受体（solubletransferrinreceptor,s—TfR）水平在慢性肾脏病（chronickidneydisease,CKD）晚期肾性贫血患者中的临床意义。方法CKD4～5期患者60例,测定血清s—TfR、铁蛋白、铁、转铁蛋白等指标水平,计算肾小球滤过率和转铁蛋白饱和度,比较CKD4期与5期患者铁状态评估指标的差异,分析s—TfR与铁蛋白及转铁蛋白饱和度的相关性。结果CKD4期患者铁蛋白、转铁蛋白饱和度明显高于5期患者,而s—TfR明显低于5期患者（P均〈0．05）;s—TfR与铁蛋白及转铁蛋白饱和度呈负相关（r=-0．398,P〈0．05;r=-0．817,P〈0．01）。结论CKD5期患者铁缺乏状态较CKD4期患者严重,s—TfR可作为判断CKD晚期肾性贫血患者体内铁缺乏的指标之     

不同贫血患儿血清可溶性转铁蛋白受体变化及其临床意义

用单克隆及多克隆双抗体夹心ＥＬＩＳＡ法测定１５例正常小儿及４６例不同贫血患儿血清可溶性转铁蛋白受体（ｓＴｆＲ），发现不同贫血患儿ｓＴｆＲ水平与对照（４．５４±１．０８ｍｇ／Ｌ）相比有显著性差异，溶血性贫血组（９．９４±３．３２ｍｇ／Ｌ）与缺铁性贫血组（１３．９２±４．４５ｍｇ／Ｌ）显著升高；再生障碍性贫血（再障）组（２．０６±０．８２ｍｇ／Ｌ）显著降低，纯红再障最低，重型再障显著低于慢性再障值。ｓＴｆＲ水平可由机体含铁状况和红系生成率共同决定，在诊断缺铁及再障的病情预后估计方面有一定临床价值。     

Novel comparison of capillary electrophoresis versus immunoassay in the measurement of total percent carbohydrate deficient transferrin

OBJECTIVES: Novel comparison of CDT isoforms as determined by CE with an FDA-approved immunoassay kit. DESIGN AND METHODS: Subjects (n=51) were categorized by drinking status based on AUDIT questionnaire responses. CDT isoform analyses by CE were compared to a commercially available, FDA-approved immunoassay. The analytical specificity of the immunoassay kit was assessed by analysis with IEF. RESULTS: Because of the poor correlation between % CDT as measured by CE and the TIA immunoassay and between subject-reported drinking levels and results from the TIA assay, extraction column eluants from the immunoassays were analyzed by IEF for analytical specificity. % CDT by TIA included some trisialo-Tf, a non-CDT fraction, in the % CDT determination. CONCLUSIONS: Total % CDT by CE, which separates all isoforms is more analytically specific than immunoassays because it does not include trisialo-Tf in the CDT calculation.     

Are the serum levels of endotoxin-binding proteins reliable predictors of complications in the course of peritonitis?

In the present study, the serum levels of the endotoxin-binding proteins transferrin, alpha 2-macroglobulin and Gc-globulin were nephelometrically determined in the morning of the first day after surgical treatment of peritonitis. The aim was to determine whether the occurrence of organ failure can be predicted by the serum levels of the described proteins. A serum level of transferrin below 1.15 g l-1 allows the prediction of organ failure with a sensitivity of 78.6% and a specificity of 81.8%. As in the case of alpha 2-macroglobulin, sensitivity and specificity reached 67.8% and 72.7% respectively at a border level of 1.05 g l-1. The predictive value of Gc-globulin, limit 0.2 g l-1, was in the same range. So the serum levels of these proteins allow an early prediction of forthcoming organ failure in the course of peritonitis. Furthermore, these results support the significance of the endotoxin interaction with these proteins.     

高血压患者血浆同型半胱氨酸和转铁蛋白的变化及氯沙坦干预的作用

目的观察高血压患者血浆同型半胱氨酸和尿转铁蛋白的变化,探讨氯沙坦对其干预作用。方法选取2009年4月一2012年4月我院就诊的轻中度高血压病患者250例为观察组,予氯沙坦50--100rng,1次／d,治疗15周;选取同期健康体检者200例为对照组。观察患者治疗前后血浆同型半胱氨酸和尿转铁蛋白的变化。结果与健康对照组比较,治疗前观察组血浆同型半胱氨酸和尿转铁蛋白水平明显升高（P均〈0．05）;氯沙坦治疗15周后与治疗前比较患者血压下降,血浆同型半胱氨酸和尿转铁蛋白水平下降（P均〈O．05）。多元线性逐步回归结果显示：血浆同型半胱氨酸是尿转铁蛋白的影响因素（P〈0．05）。结论氯沙坦可改善高血压患者早期肾损害,可能与其降低血浆同型半胱氨酸水平有关。     

转铁蛋白水平与男性生育及睾丸足细胞功能的关系

目的：探讨转铁蛋白（Tf）水平与男性生育及睾丸足细胞功能的关系。方法收集临床男性不育症患者和正常生育者的精液标本,采用精子质量分析仪进行精子密度及活动率分析,并检测精液 Tf 水平;无菌切取大鼠睾丸,经胶原酶及透明质酸酶消化,分离出纯度较高的足细胞并培养,测定细胞培养液 Tf 水平;Tf 水平测定均采用免疫速率散射比浊法。结果男性不育症患者精液 Tf 水平[（15±5）μmol／L]低于正常生育者[（24．5±6．5）μmol／L,P ＜0．01],而且与精子密度和活动率呈正相关（P ＜0．01）。正常生育组大鼠睾丸足细胞悬液 Tf 水平[（25±8）μmol／L]高于不育组[（15±6）μmol／L,P ＜0．01]。结论精液 Tf 水平的测定可作为反映足细胞功能,评价曲细精管生精功能及精子质量的指标,对男性不育症的诊断、治疗具有重要的价值。     

转铁蛋白受体及可溶性转铁蛋白受体

转铁蛋白受体（TfR）是由两个同源二聚体（180kDa）的亚基通过两条二硫键交联而成的一种II型跨膜糖蛋白,其功能是通过与转铁蛋白（If）的相互作用介导铁的吸收,其表达主要是根据细胞内铁水平进行转录后水平的调节。TfR还在细胞生长和增殖中发挥作用。最近的研究发现TfR在T细胞的激活中发挥了选择性的作用,但是具体的作用还不是完全清楚。可溶性转铁蛋白受体（sTiR）是细胞膜TfR经蛋白酶作用水解生成的分泌到血液中的组织片段,是细胞内Tffi被切断后的单体。是近年来TtR研究的一个新领域,一个新的铁代谢参数,且较稳定,不受炎症性疾病、感染、恶性肿瘤或溶血的影响,其含量与细胞的TIR量呈平行关系。本文就Tffi的结构、表达、功能以及sTiR的测定,参数界定及临床应用进行综述。     

High selenium intake and increased diabetes risk: experimental evidence for interplay between selenium and carbohydrate metabolism

The essential trace element selenium has long been considered to exhibit anti-diabetic and insulin-mimetic properties, but recent epidemiological studies indicated supranutritional selenium intake and high plasma selenium levels as possible risk factors for development of type 2 diabetes, pointing to adverse effects of selenium on carbohydrate metabolism in humans. However, increased plasma selenium levels might be both a consequence and a cause of diabetes. We summarize current evidence for an interference of selenium compounds with insulin-regulated molecular pathways, most notably the phosphoinositide-3-kinase/protein kinase B signaling cascade, which may underlie some of the pro- and anti-diabetic actions of selenium. Furthermore, we discuss reports of hyperinsulinemia, hyperglycemia and insulin resistance in mice overexpressing the selenoenzyme glutathione peroxidase 1. The peroxisomal proliferator-activated receptor gamma coactivator 1α represents a key regulator for biosynthesis of the physiological selenium transporter, selenoprotein P, as well as for hepatic gluconeogenesis. As proliferator-activated receptor gamma coactivator 1α has been shown to be up-regulated in livers of diabetic animals and to promote insulin resistance, we hypothesize that dysregulated pathways in carbohydrate metabolism and a disturbance of selenium homeostasis are linked via proliferator-activated receptor gamma coactivator 1α.     

Alarmins,COVID-19 and comorbidities

The coronavirus SARS-CoV-2, the aetiological agent of COVID-19 disease, is representing a worldwide threat for the medical community and the society at large so that it is being defined as “the twenty-first-century disease”. Often associated with a severe cytokine storm, leading to more severe cases, it is mandatory to block such occurrence early in the disease course, to prevent the patients from having more severe, sometimes fatal, outcomes. In this framework, early detection of “danger signals”, possibly represented by alarmins, can represent one of the most promising strategies to effectively tailor the disease and to better understand the underlying mechanisms eventually leading to death or severe consequences. In light of such considerations, the present article aims at evaluating the role of alarmins in patients affected by COVID-19 disease and the relationship of such compounds with the most commonly reported comorbidities. The conducted researches demonstrated yet poor literature on this specific topic, however preliminarily confirming a role for danger signals in the amplification of the inflammatory reaction associated with SARS-CoV-2 infection. As such, a number of chronic conditions, including metabolic syndrome, gastrointestinal and respiratory diseases, in turn, associated with higher levels of alarmins, both foster the infection and predispose to a worse prognosis. According to these preliminary data, prompt detection of high levels of alarmins in patients with COVID-19 and co-morbidities could suggest an immediate intense anti-inflammatory treatment.

Key message

• Alarmins have a role in the amplification of the inflammatory reaction associated with SARS-CoV-2 infection
• a prompt detection of high levels of alarmins in patients with COVID-19 could suggest an immediate intense anti-inflammatory treatment