Hypochromic erythrocytes (%): a reliable marker for recognizing iron-restricted erythropoiesis and predicting response to erythropoietin in anemic patients with myeloma and lymphoma

The aim of the study was to evaluate the role of hypochromic erythrocytes (HYPO%) compared to “traditional” and novel markers of iron status and erythropoiesis in recognizing iron-restricted erythropoiesis (IRE) and predicting response to erythropoietin (rHuEPO) in anemic patients with myeloma and lymphoma. Forty-one newly diagnosed patients who received epoetin-beta at a subcutaneous weekly dose of 30,000 IU for 6 weeks were studied. Response to rHuEPO was observed in 27 patients (65.8%). Twelve non-responders received, additionally, 200 mg of IV iron sucrose, weekly, for 4 weeks. Evaluation of markers was performed at baseline and on weeks 1, 2 and 6 for all patients and also on weeks 7–10 for non-responders to rHuEPO. Baseline HYPO%, at a cut-off value of <5%, and an increment in reticulocyte absolute number (RETICS-AB) ≥ 50,000/μl and reticulocyte hematocrit (RETICS-Hct) ≥ 50%, between baseline and week 2, were independent predictive factors for response to rHuEPO. We found that these markers had superior predictive value for response to rHuEPO than four widely used predictive models. Furthermore, a baseline HYPO% count of above 5% proved superior over serum ferritin < 100 ng/ml and transferrin saturation < 20% in recognizing IRE. In conclusion, baseline HYPO% either alone or in combination with RETICS-AB or RETICS-Hct after 2 weeks of rHuEPO treatment could be reliably used in predicting response to rHuEPO. Additionally, HYPO% has proved a reliable marker for recognizing IRE before rHuEPO treatment and, thus, could be used for identifying patients who will benefit from IV iron supplementation.     

A high-throughput test to detect C.E.R.A. doping in blood

C.E.R.A., a continuous erythropoietin receptor activator, is a new third-generation erythropoiesis-stimulating agent (ESA) that has recently been linked with abuse in endurance sports. In order to combat this new form of doping, we examined an enzyme-linked immunosorbent assay (ELISA) designed to detect the presence of C.E.R.A. in serum samples. The performance of the assay was evaluated using a pilot excretion study that involved six subjects receiving C.E.R.A. Validation data demonstrated an excellent reproducibility and ensured the applicability of the assay for anti-doping purposes. To maximize the chances of detecting the drug in serum samples, we propose the use of this specific ELISA test as a high-throughput screening method, combined with a classic isoelectric focusing test as a confirmatory assay. This strategy should make C.E.R.A. abuse relatively easy to detect, thereby preventing the future use of this drug as a doping agent.     

蔗糖铁联合促红细胞生成素治疗老年糖尿病患者慢性心衰合并贫血

目的探讨蔗糖铁联合促红细胞生成素(EPO)治疗老年糖尿病患者慢性心功能不全(CHF)合并贫血的疗效和安全性。方法2006年1月-2008年8月,解放军第四一一医院肾内科共收治36例慢性心功能不全合并贫血老年糖尿病患者;其中男性21例,女性15例;年龄均>65岁,平均(74.2±5.8)岁;血红蛋白(Hb)均<120g/L。所有患者均静脉予以蔗糖铁(200mg/个月),皮下注射EPO(3000U/次,2次/周)治疗,共12个月。治疗前及治疗第6、12个月观测纽约心脏病协会(NYHA)心功能评分、左室射血分数(LVEF)、直视模拟标度尺(VAS)评分、Hb变化及不良反应发生情况并进行对比分析。结果到治疗第12个月,Hb从治疗前的(99.1±14.2)g/L上升至(128.0±12.5)g/L;NYHA分级从(3.9±1.3)级降至(2.7±0.4)级;LVEF从(31.6%±14.1%)上升至(41.0%±12.9%);VAS从(8.4±1.6)降至(2.6±1.9),以上各指标前后对比差异均有统计学意义(P<0.05)。治疗前后收缩压(SBP)、舒张压(DBP)、血肌酐(Scr)无明显改变。无药物不良反应及并发...     

增殖性糖尿病视网膜病变微创玻璃体切割术预后影响因素

目的探讨增殖性糖尿病视网膜病变(PDR)微创玻璃体切割术(PPV)的预后影响因素及促红细胞生成素(EPO)的术前预测价值。方法 2017年 12月至 2019年 12月在重庆市江津区第二人民医院接受 PPV治疗的 PDR病人 98例 98眼的临床资料并作为 PDR组,根据术后 3月视力变化情况将其分为预后良好(n=82)、预后不良(n=16)。同期在该院进行体检的健康志愿者 100例作为正常对照组。对比 PDR组、正常对照组 EPO水平的差异,预后良好、预后不良 PDR病人 EPO水平的差异及其对预后不良的预测价值。采用单因素、多因素 logistics回归分析 PDR病人 PPV后预后不良的危险因素。结果 PDR组病人的术前 EPO水平为(13.59±2.92) U/L,正常对照组的 EPO水平为(12.16±3.21)U/L。PDR组病人的术前 EPO水平高于正常对照组,差异有统计学意义( P=0.001)。 PDR组中,预后良好者术前 EPO的水平(13.27±2.19)U/L低于预后不良者［(15.22±2.74)U/L］(P=0.002)。logistics回归分析发现:黄斑水肿严重程度 ≥500 μm、入院时收缩压 ≥140 mmHg、入院时舒张压 ≥90 mmHg及HbA1c、HDL-C、LDL-C、EPO水平较高是 PDR病人 PPV后预后不良的独立影响因素(P<0.05)。受试者工作特征(ROC)曲线显示,术前 EPO预测 PDR病人 PPV后预后不良的最佳截断值为 14.12 U/L,AUC(95%CI)为0.82(0.72~0.92),对应的灵敏度、特异度为 68.75%、71.95%。结论术前 EPO水平较高是 PDR病人 PPV后预后不良的独立危险因素,且术前 EPO水平对 PPV后预后不良具有一定预测价值。     

Erythropoietin reduces epileptogenic processes following status epilepticus

Purpose: Erythropoietin (EPO) has neuron and astroglial protective effects via reduction of tissue‐injuring molecules such as reactive oxygen species, glutamate, inflammatory cytokines, and other damaging molecules. Although EPO may constitute an effective therapeutic modality in cases of epileptic insult, no study has been performed on the effects of exogenous EPO on the chronic seizure formation. In this study, we attempted to investigate if EPO could modulate the altered microenvironment in the epileptic rat brain. Methods: Morphological changes in the hippocampi of rats subjected to lithium‐pilocarpine‐induced status epilepticus (SE) were examined with respect to neuronal loss, inflammation, blood–brain barrier (BBB) leakage, and cell genesis. Spontaneous recurrent seizures (SRSs) were investigated by long‐term video‐EEG monitoring. Results: EPO receptor (EPOR) was found to be increased in the hippocampus after SE. Administered EPO prevented, during the latent period following SE, BBB leakage, neuronal death, and microglia activation in the dentate hilus, CA1, and CA3, and inhibited the generation of ectopic granule cells in the hilus and new glia in CA1. Moreover, EPO reduced the risk of SRS development. Discussion: These findings suggest that EPO has a potential therapeutic role in the setting of acute epileptic insults.     

Protective effect of erythropoietin pretreatment in testicular ischemia-reperfusion injury in rats

Background/Purpose

This study was designed to investigate the effects of recombinant erythropoietin (EPO), a hormone widely used for treatment of uremic anemia, in rats subjected to testicular ischemia and reperfusion (I/R).

Methods

Thirty-five male rats were divided into the following: control, sham operated, ischemia (I), I/R, and I/R + EPO groups. In the I group, 2 hours of left unilateral testicular torsion were performed, and in the I/R and I/R + EPO groups, an additional 2 hours of testicular detorsions were performed. The I/R + EPO group was pretreated intraperitoneally with EPO (500 IU/kg) before reperfusion. Testicular tissue samples were examined for biochemical and histopathologic parameters. Apoptotic cells in all testes were detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling technique and caspase 3 immunohistochemistry.

Results

At histopathologic examination, ischemic changes in primary spermatocytes were noted in all torted testes. Cellular damage and apoptosis were more severe in ischemic groups than the EPO-pretreated group. There were statistically significant differences in tissue biochemical parameters in the I and I/R groups compared with the I/R + EPO group.

Conclusions

The results of the present study suggest that EPO exerts protective effects against I/R injury via the modulation of free radical scavenger's activities, which decreases lipid peroxidation levels and attenuation of apoptosis.     

慢性病性贫血的研究进展

慢性感染、炎症及肿瘤性疾病所伴有的贫血通常称为慢性病贫血（ACD），是临床最常见的综合征之一，本病以介导免疫或炎症反应的细胞因子（如肿瘤坏死因子、白细胞介素－1有干扰素等产生增多为特征，ACD演变的全过程均与细胞因子有关，包括红细胞寿命缩短，对促红细胞生成素（EPO）的反应迟缓、红细胞系集落生成受损以及网状内皮系统贮存铁动员障碍，本文就慢性病性贫血的定义，诊断、病理生理及治疗进展进行综述。     

Potential role of Ca++ on the differentiation of erythroid progenitor cells

In order to gain insight into the mechanisms by which erythropoietin promotes erythropoiesis, effects of various inhibitors on the erythropoietin-promoted differentiation of erythroid progenitor cells and on the erythropoietin-promoted Ca⁺⁺ uptake in the progenitor cells were determined, and the relationship between the inhibitory activity of each inhibitor toward the differentiation and Ca⁺⁺ uptake were examined. The inhibitors used were a tyrosine kinase inhibitor (genistein), a Ca⁺⁺-channel blocker (verapamil), a Ca⁺⁺ chelator (EDTA) and a protein kinase C inhibitor (staurosporine). All of these agents inhibited both the erythropoietin-mediated differentiation of the erythroid progenitor cells, as determined by the incorporation of⁵⁹Fe into heme, and Ca⁺⁺ uptake in a concentration dependent manner. In the cases of verapamil and EDTA, the half-miximal inhibitory concentration (IC₅₀) values for differentiation of the progenitor cells may be the consequence of the inhibition of the Ca⁺⁺ uptake by the inhibitior. On the other hand, in the cases of genistein and staurosporine, the IC₅₀ values for inhibition of differentiation were significantly different from that for inhibition of Ca⁺⁺ uptake. These results suggest that the mechanism of inhibition of differentiation by these two inhibitors is complex. However, taken all together, the above results support the proposition that Ca⁺⁺ uptake may paly a role in the erythropoietin-mediated differentiation of erythoid progenitor cells.     

低氧条件下动物网织红细胞的EPO依赖效应

小鼠暴露于低氧（低压舱０．４２ａｔｍ，２２ｈ／ｄａｙ）期间，观察投用促红细胞生成素（ＥＰＯ）对红细胞生成的影响。结果表明，网织红细胞的生成与释放对ＥＰＯ存在一定剂量依赖效应。低氧早期骨髓的红细胞生成对ＥＰＯ具有高度敏感性；随低氧持续作用，骨髓对ＥＰＯ的敏感性降低。提示较高水平ＥＰＯ的持续作用对网织红细胞生成与释放具有反馈性抑制作用。     

The influence of steroid therapy and recombinant human erythropoietin on the growth of children with renal disease

Long-term steroid therapy has a depressant effect on hypothalamo-pituitary pulsatile secretion of growth hormone (GH), and this results in an attenuated pubertal growth spurt. Oxandrolone and recombinant human GH improve growth rates in children taking long-term steroid therapy for renal disease, but there are potential side effects. Treatment with recombinant human erythropoietin improved the growth of three prepubertal, but not three pubertal haemodialysis patients.