右旋糖苷铁与促红细胞生成素治疗肾性贫血

目的：比较静脉补铁与口服补铁对血液透析患者肾性贫血的疗效及不良反应。方法：将50例血液透析伴有肾性贫血的患者，随机分为：①治疗组（静脉补铁组）25例，右旋糖苷铁注射液100mg，每次血液透析中使用，每周2次，共10次。②对照组（口服补铁组）25例。多糖铁胶囊150mg，po qd。观察8周。50例合并使用促红细胞生成素（EPO），每周8000U，sc。观察并比较两组患者治疗贫血的效果、铁代谢指标的变化及不良反应。结果：治疗后，两组患者的Hb、Hct及血清铁蛋白（SP）均较治疗前显著升高（P〈0．01），但治疗组显著高于对照组（P〈0．05）。总有效率分别为88％与65％（P〈0．05），均无不良反应。结论：静脉补铁的疗效明显高于口服补铁。     

促红细胞生成素对人视网膜色素上皮细胞氧化损伤保护作用及其机制

目的 观察促红细胞生成素（EPO）对人视网膜色素上皮（hRPE）细胞抗过氧化氢（H₂O₂）损伤的影响。方法以传代培养hRPE细胞为研究对象, 采用800μmol/L H₂O₂ 作用3 h 建立 hRPE 细胞损伤模型, 分为正常对照组、单纯损伤组、重组人EPO（rhEPO）治疗组。治疗组又根据加入rhEPO浓度不同分为10、20、40、60 IU/ml亚组。免疫组织化学方法检测细胞中核因子kappa B(NF-κB)的活化情况，比色法测定细胞脂质过氧化产物丙二醛（MDA）含量及乳酸脱氢酶（LDH）细胞释放率。结果 H₂O₂ 可使培养液中MDA及LDH释放率上升，单纯损伤组与正常对照组相比，差异有统计学意义（t_LDH＝29.746，t_MDA＝20.426，P＜0.05）；各治疗组与单纯损伤组比较，MDA及LDH释放率均有显著降低，差异有统计学意义（t_10IU＝5.770，t_20IU＝12.774，t_40IU＝19.818，t_60IU＝24.833，P＜0.05；MDA t_10IU＝5.345，t_20IU＝10.278，t_40IU＝18.571，t_60IU＝20.247，P＜0.05）；各治疗组相关分析显示，rhEPO浓度与LDH细胞释放率及MDA含量呈负相关（r=-0.976，P=0.024； r=-0.968，P=0.032）；rhEPO浓度与NF-κB核移位率呈正相关（r=0.998，P=0.002）；NF-κB核移位率与MDA含量呈负相关（r=-0.954，P=0.046）。结论 EPO能有效地拮抗 H₂O₂ 对hRPE细胞的脂质过氧化损害，其机制可能与活化NF-κB有关。     

维持性血液透析对T细胞亚群与红细胞生成素低反应性的影响

目的 通过对红细胞生成素(rHuEPO)不同反应的患者用流式细胞仪检测T细胞亚群以了解rHuEPO低反应与细胞免疫的关系及可能的作用机制.方法 将40例维持性血液透析(MHD)患者按照rHuEPO反应的不同分为第一组和第二组,rHuEPO反应低下的18例为第一组,rHuEPO反应良好的22例为第二组,另设一健康对照组20例.应用流式细胞仪检测各组患者T淋巴细胞表面CD+4、CD+8、CD+4/CD+28、CD+8/CD+28抗原的表达情况.结果 rHuEPO反应良好组和反应低下组的CD+4 T细胞、CD+8 T细胞百分比差异无统计学意义,但均显著低于对照组;rHuEPO反应低下组的CD+4 CD+28/CD+4、CD+8 CD+28/CD+8 T细胞的百分比明显低于反应良好组和对照组,而反应良好组与对照组之间无明显差异.结论 尿毒症MHD患者存在T细胞免疫表型的改变.     

慢性肾功能衰竭伴肾性贫血患者促红细胞生成素水平的变化

目的检测慢性肾功能衰竭(CRF)伴肾性贫血患者血清促红细胞生成素(EPO)水平的变化,并探讨其临床应用价值及意义。方法用ELISA法检测40例CRF伴肾性贫血患者治疗前后和30例健康对照者(肾功能正常且无贫血)血清中EPO、血细胞分析仪检测Hb、RBC和HCT水平。结果经治疗后患者EPO水平有明显下降,差异有统计学意义(P<0.01),Hb、RBC和HCT水平均较治疗前显著升高,差异有统计学意义(P<0.01),但与健康对照组比较差异仍有统计学意义(P<0.01)。结论CRF伴肾性贫血患者EPO含量增高,经过治疗,EPO水平虽有下降,但仍然高于正常值,可见EPO与CRF伴肾性贫血的发生有关。     

Impact of erythropoietin on the reduction of blood transfusions and on survival of lung cancer patients receiving first-line chemotherapy

INTRODUCTION: Anaemia is a common problem in patients with cancer who receive chemotherapy and is normally associated with a negative impact on patients' quality of life (QOL), poor cancer control and diminished survival. In clinical trials, recombinant human erythropoietin has been shown to correct and prevent anaemia, decrease the need for blood transfusions and improve cancer patients' QOL. METHODS: A retrospective study followed lung cancer patients who received first-line chemotherapy in our hospital in 1998 and in 2005. The incidence of anaemia was analysed, as was the impact of incorporating erythropoietin into the treatment. RESULTS: The incidence of anaemia was 68% (69% of which reported asthenia) in 1998 vs. 54% (60% with asthenia) in 2005. The comparison of anaemia rates (1998 vs. 2005) were grade 1 (16% vs. 32%), grade 2 (36% vs. 16%), grade 3 (16% vs. 5%) and grade 4 (none). Treatment for anaemia included transfusion 52%, intravenous iron 5% and epoetin 4% in 1998. In 2005 anaemia was treated with transfusion 9%, intravenous iron 41%, and epoetin 49%. Median survival (1998 vs. 2005) was 242 days [95% confidence interval (CI) 217-329) vs. 356 days (95% CI 322-382). CONCLUSIONS: Erythropoietin is a valid alternative for cancer patients with anaemia undergoing chemotherapy. It can possibly avoid the need for transfusions without negatively impacting survival.     

New alternatives for erythropoietin therapy in chronic renal failure

Erythropoietin (EPO) is one of the main cytokines involved in the regulation of erythropoiesis. The main site of EPO production are the kidneys. An altered EPO production leads to pathological conditions such as anemia and polycythaemia. Due to the progressive loss of renal peritubular cells, patients with chronic kidney disease (CKD) have low EPO plasma levels. This decreases erythron stimulation with the direct consequence of developing anemia. Before the introduction in the clinical practice of rHuEpo, in the late 1980s, the only solution for treating this type of anemia were blood transfusions and anabolic steroids. Even rHuEpo has proven to be safe and effective for treatment of anemias, there are some concerns about its cost, the need for frequent parenteral administration, and development of anti-EPO antibodies. These inconveniences prompted the search for novel erythropoiesis stimulating agents. Different strategies lead to isolation or chemical synthesis of such agents as darbepoetin alfa and EPO mimetics. In this review, we present some general aspects of EPO biology, with emphasis on chronic renal failure, and expose some of the alternatives to EPO used for anemia correction.     

促红细胞生成素对大鼠脑缺血再灌注损伤的保护作用

目的:探讨促红细胞生成素(Epo)对大鼠局灶性脑缺血再灌注后脑损伤的保护作用。方法:20只雄性SD大鼠,采用线栓法阻断大鼠一侧大脑中动脉(MCA)血流2h,再灌注48h制成局灶性脑缺血再灌注损伤模型。随机分为两组,治疗组于再灌注前经腹腔注射Epo(3000U/kg),对照组给予等量生理盐水腹腔注射,48h后断头取脑。制作2mm冰冻切片;以2%氯化-2,3,5三苯基四氮唑(TTC)对脑切片进行染色;经图像分析仪计算梗死体积占全脑体积的百分比。结果:治疗组脑梗死体积与对照组相比明显缩小(P<0.01)。结论:Epo能够显著缩小脑梗死体积,对脑缺血再灌注损伤有良好的保护作用。     

促红细胞生成素对心血管保护作用的研究进展

促红细胞生成素(EPO)是特异性作用于红系祖细胞的造血生长因子,但新近有证据表明,EPO具有重要的心脏保护功能。啮齿类动物心肌缺血实验显示,EPO能显著降低心肌梗死面积,改善左心室功能;使用EPO治疗合并贫血的慢性心力衰竭(CHF)患者,可显著改善患者的心功能及临床症状。尽管EPO在治疗肾性贫血过程中可能有导致血压增高、血栓形成的危险,但EPO治疗心肌缺血和CHF是安全的。目前,对EPO所介导的细胞内信号转导路径已有所认识,有可能开辟治疗心血管疾病的新途径。     

Erythropoietin and granulocyte-macrophage colony-stimulating factor allow acceleration and dose escalation of cyclophosphamide/epidoxorubicin/5-fluorouracil chemotherapy: a dose-finding study in patients with advanced breast cancer

 To verify whether the association of granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (EPO) would allow both the acceleration and the dose escalation of the cyclophosphamide/epidoxorubicin/5-fluorouracil (CEF) regimen as first-line therapy in advanced breast cancer patients, we conducted a dose-finding study. Cohorts of three consecutive patients received cyclophosphamide (Ctx, dose range 800 –1400 mg/m²), epidoxorubicin (Epidx, dose range 70–100 mg/m²), and 5-fluorouracil (5-Fu, 600 mg/m², fixed dose) given as an intravenous bolus on day 1 every 14 days; GM-CSF at 5 μg/kg given as a subcutaneous injection from day 4 to day 11; and EPO at 150 IU/kg given as a subcutaneous injection three times a week. In no single patient was any dose escalation allowed. A total of 14 patients entered the study. At the 4th dose level (Ctx 1400 mg/m², Epidx 100 mg/m², 5-Fu 600 mg/m²), two patients had dose-limiting mucositis and one patient developed dose-limiting neutropenia. Therefore, the 3rd cohort received the maximum tolerated dose, i.e. Ctx at 1200 mg/m², Epidx at 90 mg/m², and 5-Fu at 600 mg/m², given every 18.5 (±2.5) days. Toxicity was moderate and manageable in an outpatient setting. Only 1 admission at the 4th dose level was required. Throughout the 4 dose levels there was no toxicity-related death; grade IV leukopenia ranged from 24% to 75% of cycles and grade IV thrombocytopenia ranged from 6% to 8%. No grade IV anemia was recorded. Increasing the doses of Ctx and Epidx while maintaining a fixed dose of 5-Fu with the support of both EPO and GM-CSF allows safe acceleration and dose escalation of CEF chemotherapy. Further controlled studies will evaluate the activity and efficacy of this strategy. Received: 8 October 1995/Accepted: 1 March 1996     

7,12-DMBA-induced rat leukemia: a review with insights into future research

7,12-Dimethylbenz[a]anthracene (DMBA) elicits leukemia in Long–Evans rats (LE). This leukemia is mostly erythroblastic and 30% of leukemias have total and partial trisomy of #2 chromosome and the rest have diploid karyotype. The common duplication site is in 2q26–q34 and N-ras gene is located in 2q34. 7,8,12-Trimethylbenz[a]anthracene (TMBA) also induces similar leukemias. These leukemias reveal a highly specific mutation of N-ras gene as in human leukemias. N-ras mutation is induced 48 h after DMBA treatment. Wild type N-ras allele is frequently lost in diploid leukemias but not in trisomy type. Therefore, a gene dosage problem related to the mutant N-ras gene is involved in development of leukemia. Some secondary genetic rearrangements involving abl and H-ras are also observed in cultured leukemia cells. DMBA-induced chromosome aberrations as well as leukemia are enhanced by erythropoietin and blocked by Sudan III given prior to DMBA treatment. This leukemia will provide an important tool for chemical carcinogenesis and leukemia studies.