OBJECTIVETo investigate the effect of intranasal administration of low dosage recombinant human erythropoietin (r-HuEPO) on seizure in rats.

METHODSAfter intranasal or intraperitoneal administration of r-HuEPO, the behavioral and electroencephalographic changes were observed in pentylenetetrazol (PTZ) and maximal electroshock (MES) induced seizure or electrical amygdaloid-kindled seizure of rats.

RESULTIntranasal administration of low dosage r-HuEPO increased the seizure latency, and decreased the seizure grade and duration, and the number of convulsive episodes in PTZ induced seizure, with the most potential dosage of 2.4 IU. Intraperitoneal administration of r-HuEPO (3 000, 4 000 IU/kg) only decreased the seizure duration and number of convulsive episodes. The seizure grade, forelimb or hindlimb extension duration were decreased in MES-induced seizure by intranasal administration of 2.4 IU r-HuEPO. In addition, intranasal administration of 2.4 IU r-HuEPO decreased the seizure grade, generalized seizure duration and afterdischarge in electrical amygdaloid-kindled rats stimulated with generalized seizure threshold.

CONCLUSIONIntranasal administration of low dosage r-HuEPO can inhibit the seizure in rats.

Administration, Intranasal ; Animals ; Anticonvulsants ; administration & dosage ; Epilepsy ; chemically induced ; drug therapy ; Erythropoietin ; administration & dosage ; Humans ; Male ; Pentylenetetrazole ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins

Erythropoietin combined with parenteral iron sucrose therapy is an alternative to blood transfusion in anemic patients. It was shown to be effective in surgical patients in several previous studies when used in conjunction with other methods. However, there are no guidelines about safety limits in dosage amounts or intervals. In this study, we report a case of significant postoperative hemorrhage managed with high dose parenteral iron sucrose, low dose erythropoietin, vitamin B12, vitamin C, and folic acid. An 80-year-old female patient presented for severe anemia after a total hip arthroplasty and refused an allogenic blood transfusion as treatment. The preoperative hemoglobin of 12.2 g/dL decreased to 5.3 g/dL postoperatively. She received the aforementioned combination of iron sucrose, erythropoietin, and vitamins. A total of 1,500 mg of intravenous iron sucrose was given postoperatively for 6 consecutive days. Erythropoietin was also administered at 2,000 IU every other day for a total of 12,000 IU. The patient was discharged in good condition on the twelfth postoperative day with a hemoglobin of 8.5 g/dL. Her hemoglobin was at 11.2 g/dL on the twentieth postoperative day.
Aged ; Aged, 80 and over ; Anemia/*drug therapy ; Arthroplasty, Replacement, Hip/*adverse effects ; Blood Transfusion ; Drug Therapy, Combination ; Erythropoietin/*administration & dosage ; Female ; Ferric Compounds/*administration & dosage ; Humans

Genetic polymorphisms may be linked to inter-individual differences in erythropoietin (EPO) resistance. We investigated the -511C/T polymorphism of the IL-1B gene and the I/D polymorphism of the ACE gene for any association with EPO resistance index (ERI) in maintenance hemodialysis patients (n=167). Because EPO responsiveness is multi-factorial, we also included other possible influences (age, sex, time on dialysis, ACE inhibitor or angiotensin receptor blocker use, ferritin, transferrin saturation, intact PTH, high sensitivity C-reactive protein, albumin, Kt/V, and presence of diabetes mellitus) on ERI in our analyses. Multiple regression analysis showed significant association of the IL-1B-511CC and ACE DD polymorphisms with ERI (P=0.038 and P=0.004 in the recessive model, respectively). The combination (C) of alleles of two loci showed that C1 (I-T) was significantly associated with ERI in the co-dominant and recessive models (P=0.005 and P=0.0001, respectively). Subjects who did not carry C1 showed significantly decreased ERI (10.10+/-5.15 IU/kg weight/g hemoglobin) compared to other study subjects (C1/C1 and C1/-; 12.97+/-4.90 and 15.12+/-7.43 IU/kg weight/g hemoglobin, respectively). Our study indicates that the IL-1B-511C/T and ACE I/D polymorphisms may be useful genetic markers of EPO requirement in hemodialysis patients. These findings might also provide a new perspective on therapeutic approaches to the treatment of end stage renal disease patients with anemia.
Adult ; Aged ; *Drug Resistance ; Erythropoietin/*administration & dosage ; Female ; Humans ; Interleukin-1beta/*genetics ; Korea ; Male ; Middle Aged ; Peptidyl-Dipeptidase A/*genetics ; *Polymorphism, Genetic ; *Renal Dialysis

OBJECTIVESTo observe the change of erythropoietin (EPO) in patients of hypogonadism who received androgen replacement treatment and explore the mechanism of androgen-induced increase of red blood cells and haemoglobin.

METHODSEight patients with Klinefelter's syndrome, divided into two groups, received TU intramuscular injections of 500 mg or 1000 mg dose, respectively. After three months, seven patients received the second injection of crossover dose. Testosterone levels in serum were measured with RIA before and after the injections treatment. RBC count, impacted volume of blood cells and haemoglobin concentration were measured before treatment and 4, 8 weeks after treatment. At the same interval, EPO levels were measured with ELISA method.

RESULTSDevelopment of the secondary sex characters was improved in all patients after the TU injection. Serum testosterone levels raised significantly and reached the peak one week after the injections. Effective level of testosterone lasted for over 6 weeks. RBC count, impacted volume of blood cells and haemoglobin increased at different degrees after TU injections, but these changes were not significant in statistic(P < 0.05). The increased levels remained for 8 weeks. EPO levels were elevated significantly (P < 0.01 or 0.05) after the TU injection(Pbat > 0.05). The second injection could still make the EPO level go up.

CONCLUSIONSAndrogen replacement treatment can increase the EPO levels in patients of hypogonadism, which is one of the mechanism of RBC production increase.

Adolescent ; Adult ; Enzyme-Linked Immunosorbent Assay ; Erythropoietin ; blood ; Humans ; Injections, Intramuscular ; Klinefelter Syndrome ; blood ; drug therapy ; Male ; Radioimmunoassay ; Testosterone ; administration & dosage ; analogs & derivatives ; blood ; therapeutic use

The aim of this study was to investigate the curative effects of amifostine (AMF) combined with recombinant human beta-erythropoietin (rhbeta-EPO) on patients with pure erythroid aplasia (PEA). Two patients with PEA were treated with amifostine and rhbeta-EPO. The therapeutic regimen was adopted with AMF 0.4 g/day given by intravenous injection for 5 days first, then after a break of 2 days it went on for 3 weeks consecutively, that was considered as one treatment cycle. The rhbeta-EPO 6 000 U was used by subcutaneous injection for 3 times per week. The results showed that the red cell count, hemoglobin and reticulocyte count of two patients obviously increased after treatment. The erythroid ratio in bone marrow increased. Bone marrow biopsy showed that the erythroid proliferation improved. Intervals of red cell transfusions (RCT) in the two patients who live by red cell transfusion were prolonged after AMF treatments, and the amounts of each RCT was decreased obviously. The main side effect of amifostine was discomfort of digestive system, but was tolerated by all patients. In conclusion, amifostine plus rhbeta-EPO may be a new, effective and safety method especially for the elder PEA patients. The long-term curative effects and mechanism of amifostine still need further evaluation.
Aged, 80 and over ; Amifostine ; adverse effects ; therapeutic use ; Anemia, Aplastic ; drug therapy ; Drug Therapy, Combination ; Erythropoietin ; administration & dosage ; therapeutic use ; Humans ; Male ; Recombinant Proteins ; Treatment Outcome

Patient blood management (PBM) is an evidence-based, patient-focused approach to optimize the management of patient and blood transfusion. While PBM is relatively well established in perioperative care, it is not as well established in the medical field. Since anemia in medical patients is heterogeneous and complex in its pathogenesis, the evidence for the threshold of hemoglobin for red blood cell (RBC) transfusion and the use of erythropoiesis-stimulating agents (ESAs) is not strong. While anemia seems to be an adverse risk factor for mortality, it is uncertain if rapid correction of anemia through RBC transfusion can reverse the negative impact of anemia on clinical outcomes. The introduction of ESA is a breakthrough in reducing RBC transfusion and managing anemic patients with renal disease and cancer. Despite promising results from early trials, the United States Food and Drug Administration issued a black box warning for ESAs in 2007 because of concerns about higher mortality, serious cardiovascular and thromboembolic events, and tumor progression. Therefore, the individualized approach to each patient with anemia is recommended in various medical conditions such as acute coronary syndrome, heart failure, chronic kidney disease, and malignancies.
Acute Coronary Syndrome ; Anemia ; Blood Transfusion ; Drug Labeling ; Erythrocytes ; Erythropoietin ; Heart Failure ; Humans ; Iron ; Mortality ; Perioperative Care ; Renal Insufficiency, Chronic ; Risk Factors ; United States Food and Drug Administration

To determine the efficacy and tolerance to cyclosporine A (CsA) based therapy in patients with myelodysplastic syndrome (MDS), 16 patients with MDS consisting of 10 refractory anemia (RA) and 6 refractory anemia with accessory blasts less than 10% (RAEB-1) were analyzed. Five patients had hypocellular bone marrows and 11 patients had normocellular or hypercellular marrows. The dose of CsA was 2.5-5.5 mg/(kg.d) for 2 weeks to 2 years (mean 8 months). Two out of 16 patients were treated with CsA alone, 14 patients were treated with CsA, recombinant human erythropoietin, androgens, 1, 25 dihydroxy vitamin D(3) or two or three of them combination with CsA. Treatment responses were classified according to the International Working Group (IWG) criteria as complete remission (CR), partial remission (PR), hematological improvement (HI) and no response (NR). Patients who obtained CR, PR or HI were defined as responders. The results showed that HI was observed in 12 patients, PR in 2 patients and NR in 2 patients. Total response rate was 87.5%. Response rates shown in neutrophil lineage, platelet and erythroid lineage were 83.3%, 66.7% and 60%, respectively; their shortest time required to obtain some hematologic improvement after initiation of CsA therapy was 2 weeks, 1 month and 1 month, respectively. Of 13 patients being transfusion-dependent before treatment, 3 patients did not need transfusion any more and 5 showed the reduced transfusion requirements after CsA therapy. In 10 patients with RA, 9 responded to CsA. Of 6 patients with RAEB, 1 patient had no response and died of RAEB-t and 5 patients had transient responses. One of the latter transformed to CMML and two relapsed. The total response rate decreased to 50% in the patients with CsA therapy lasting more than 3 months at the end of following-up. The adverse effects included hirsutism, hyperplastic gingiva, reversible hepatic and renal dysfunction. In conclusion, the usefulness of CsA based therapy for MDS-RA and RAEB-1 with any marrow cellularity is useful, the CsA dose of 3-5 mg/(kg.d) is safe and efficacious.
Adolescent ; Adult ; Aged ; Androgens ; administration & dosage ; Anemia, Refractory ; drug therapy ; Anemia, Refractory, with Excess of Blasts ; drug therapy ; Calcitriol ; administration & dosage ; therapeutic use ; Cyclosporine ; administration & dosage ; therapeutic use ; Drug Therapy, Combination ; Erythropoietin ; administration & dosage ; therapeutic use ; Female ; Humans ; Immunosuppressive Agents ; administration & dosage ; therapeutic use ; Male ; Middle Aged ; Myelodysplastic Syndromes ; drug therapy ; Recombinant Proteins ; Treatment Outcome

This study was performed to evaluate whether increasing hemoglobin before ascent by prophylactic erythropoietin injections prevents acute mountain sickness (AMS). This open-label, randomized, controlled trial involved 39 healthy volunteers with hemoglobin < or =15.5 g/dL who were divided randomly into erythropoietin (n=20) and control (n=19) groups. Epoetin alpha 10,000 IU injections were given weekly for four consecutive weeks. On day 1, and 7 days after the last injection (day 29), oxygen saturation (SaO2), and hemoglobin were measured. The subjects departed Seoul on day 30 and arrived at Annapurna base camp (ABC, 4,130 m) on day 34. AMS was diagnosed when headache and Lake Louise score (LLS) of > or =3 were present. Immediate descent criteria followed US Army recommendations. Two groups differ in hemoglobin levels on day 29 (15.4+/-1.1 vs 14.2+/-1.0 g/dL, P=0.001). At ABC, erythropoietin group had a significantly lower mean LLS, AMS incidence, and number of subjects who met immediate descent criteria. Multiple logistic regression analysis showed that SaO2<87% and control group, but not hemoglobin<15.0 g/dL, independently predicted satisfaction of immediate descent criteria. Erythropoietin-related adverse effects were not observed. In conclusion, erythropoietin may be an effective prophylaxis for AMS.(Clinical Trial Registry Number; NCT 01665781).
Acute Disease ; Adult ; Altitude Sickness/diagnosis/epidemiology/*prevention & control ; Blood Pressure/physiology ; Drug Administration Schedule ; Erythropoietin/*therapeutic use ; Female ; Headache/physiopathology ; Hemoglobins/analysis ; Humans ; Incidence ; Logistic Models ; Male ; Middle Aged ; Odds Ratio ; Oxygen/blood ; Questionnaires ; Recombinant Proteins/therapeutic use

OBJECTIVETo compare the effect on erythropoietin (Epo) resistance between acupoint injection and subcutaneous injection of rHuEpo in patients with chronic renal failure (CRF).

METHODSThirty-eight cases were randomly divided into two groups, 19 cases in each one. In subcutaneous injection group (control group), subcutaneous injection of rHuEpo was administered, 3 times a week, lasting 2 months. In acupoint group (observation group), rHuEpo was injected on unilateral Shenshu (BL 23) and Zusanli (ST 36), one point was chosen each time, the bilateral acupoints were injected alternatively, 3 times a week, for 2 months. Meanwhile, a normal control group of 19 healthy persons was set up. The levels of CRP, IL-6, TNF-alpha, Scr, BUN, Hb, Hct and SF were observed.

RESULTSBefore treatment, the values of CRP, IL-6 and TNF-alpha in two groups were all higher than those in normal control group (all P < 0.01). After treatment for 2 months, the values of CRP, IL-6,TNF-alpha, Scr and BUN in two groups decreased apparently and those of Hb, Hct and SF increased obviously, indicating statistic significant differences as compared with the values before treatment separately (P < 0.05, P < 0.01). In comparison between two groups after treatment, every index above in observation group was improved much significantly (P < 0.05, P < 0.01).

CONCLUSIONAcupoint injection of rHuEpo at Zusanli (ST 36) and Shenshu (BL 23) increases significantly the values of Hb, Hct and SF, and decreases apparently the values of BUN, Scr and inflammatory factors, such as CRP, IL-6 and TNF-alpha as compared with subcutaneous injection. Acupoint injection improves Epo resistance and enhances Epo efficacy via alleviating micro-inflammatory state of the body.

Acupuncture Points ; Adult ; Aged ; Drug Resistance ; Erythropoietin ; administration & dosage ; Female ; Humans ; Inflammation Mediators ; blood ; immunology ; Injections, Subcutaneous ; Interleukin-6 ; blood ; immunology ; Kidney Failure, Chronic ; blood ; drug therapy ; immunology ; Male ; Middle Aged ; Recombinant Proteins ; Tumor Necrosis Factor-alpha ; blood ; immunology

OBJECTIVEOxygen toxicity is thought to be a major contributing factor in the pathogenesis of bronchopulmonary dysplasia (BPD). Animal experiments reveal that erythropoietin (EPO) may have protective effects against hyperoxic lung injury, but the mechanisms remain unknown. The aim of this study was to evaluate effects of hyperoxia on erythropoietin receptor expression in lung development of neonatal rats.

METHODSSeveral litters of Wistar pups were pooled together within 12 hours after birth and randomly divided into two groups (n = 24 in each): air-exposed control group and hyperoxia-exposed group. In hyperoxia-exposed group, the rats were exposed to 85% oxygen. Pups (n = 8) from each group were sacrificed on postnatal days 3, 7, and 14. The pulmonary histological and morphometric changes were observed after hematoxylin-eosin (HE) staining under light microscope. Radical alveolar counts (RAC) were compared between the two groups to evaluate the differences of alveolarization. Expressions of platelet endothelial cell adhesion molecule-1 (PECAM-1) and erythropoietin receptor (EPOR) in lung tissue were measured by immunohistochemistry. Expressions of EPOR mRNA and EPOR protein were measured by RT-PCR and Western blotting.

RESULTSIn hyperoxia-exposed group, there were a few inflammatory cells infiltration in interstitium on day 3 and inflammatory response worsened on day 7. Alveolar and capillary hypoplasia and interstitial fibrosis were evident on day 14. RAC increased in air-exposed control group along with the age in days. RAC decreased from day 7 in hyperoxia-exposed group compared with air-exposed control group [(6.85 ± 1.04) vs. (7.33 ± 1.0), P < 0.01], which was more evident on day 14 [(6.20 ± 1.58) vs. (9.07 ± 0.69), P < 0.001]. Expression of PECAM-1 protein increased in air-exposed control group along with the age in days. But in hyperoxia-exposed group, it decreased on day 7 and 14 [(15.14 ± 1.51) vs. (31.47 ± 2.43), (11.04 ± 1.76) vs. (41.41 ± 3.83), P < 0.001] compared with air-exposed control group. Expression of EPOR on day 3 in air-exposed control group was the strongest and weakened gradually with the increase of postnatal days. Expression of EPOR in hyperoxia-exposed group decreased on day 3 and became more evident on day 7 and day 14 compared with air-exposed control group [(1.62 ± 0.04) vs. (1.82 ± 0.06), P < 0.05; (0.48 ± 0.01) vs. (1.10 ± 0.07), (0.39 ± 0.04) vs. (0.87 ± 0.03), P < 0.001]. Expression of EPOR mRNA on day 3 in air-exposed control group was the strongest and was decreased significantly in hyperoxia-exposed group compared with air-exposed control group at all time points [(0.87 ± 0.07) vs. (1.1 ± 0.17), (0.18 ± 0.07) vs. (0.36 ± 0.08), P < 0.01;(0.14 ± 0.05) vs. (0.36 ± 0.09), P < 0.001].

CONCLUSIONSEPOR may participate in the modulation of normal lung development. Depressed expression of EPOR and PECAM-1 may be involved in the pathogenesis of alveolar and capillary hypoplasia induced by hyperoxia.

Animals ; Animals, Newborn ; Disease Models, Animal ; Female ; Lung Injury ; etiology ; metabolism ; Male ; Oxygen ; administration & dosage ; adverse effects ; Platelet Endothelial Cell Adhesion Molecule-1 ; metabolism ; Pulmonary Alveoli ; drug effects ; metabolism ; Rats ; Rats, Wistar ; Receptors, Erythropoietin ; metabolism