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

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

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

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

BACKGROUND: Recombiant human erythropoietin (epoetin) has greatly contributed to improvement of the anemia of chronic renal failure patients on hemodialysis. However, the reduced erythropoietic effect to epoetin and its high cost have induced lots of supplementary treatments. Therefore, we performed a prospective study to evaluate the effects of adjuvant low-dose androgen therapy in patients using a lower-dose of epoetin than the commonly recommended dose on anemia and the nutritional parameters. METHODS: 17 patients of hemoglobin (Hgb) less than 9 g/dL even after being treated with 1,000 U epoetin subcutaneously (s.c.) 3 times per week on a stable status for more than 6 months, who were on hemodialysis at our institution were examined. They were injected with the same dose of epoetin s.c. and nandrolone decanoate 100 mg intramuscularly (i.m) weekly for another 6 months. Blood test was performed every month before therapy for 6 months and after therapy for 6 months and the mean values were reviewed for comparison. RESULTS: Hgb (7.75+/-0.9 vs 8.99+/-1.39 g/dL, p < 0.01) and hematocrit (Hct) (23.68+/-2.85 vs 26.66+/-3.91%, p < 0.01) were apparently changed before and after adjuvant therapy. Hgb and Hct, weekly dose of epoetin were not statistically different in 9 male patients before and after adjuvant therapy. The weekly dose of epoetin was not statistically different in 8 female patients, but Hgb and Hct (8.02+/-0.6 vs 9.72+/-1.31 g/dL, 24.54+/-1.7 vs 28.74+/-3.06%, p < 0.01) were statistically different before and after adjuvant therapy. In comparison between male and female groups, weekly doses of epoetin and nandrolone decanoate were significantly greater in the female group than the male group (epoetin; 50.66+/-6.23 vs 61.18+/-8.76 U/kg/week, nandrolone decanoate; 1.69+/-0.2 vs 2.04+/-0.29 mg/kg/week, p < 0.05). CONCLUSION: Our data show that the adjuvant androgen therapy is effective for the anemia of hemodialysis patients who did not recover from anemia even after being continuously treated with low-dose epoetin.
Adult ; Anabolic Steroids/*administration & dosage/blood ; Anemia, Aplastic/blood/*drug therapy ; Chemotherapy, Adjuvant ; Erythropoiesis/drug effects ; Erythropoietin, Recombinant/*administration & dosage/blood ; Female ; Human ; Kidney Failure, Chronic/blood/drug therapy ; Male ; Middle Age ; Nandrolone/*administration & dosage/blood ; Nutritional Status ; Prospective Studies ; *Renal Dialysis

OBJECTIVETo investigate the efficacy and impact factors in lower-risk [International prognostic scoring system (IPSS) low or intermediate-1 risk] myelodysplastic syndrome (MDS) patients treated with recombinant human erythropoietin (rhEPO) alone or in combination with recombinant human granulocyte colony- stimulating factor (rhG-CSF).

METHODSA total of 52 consecutive lower-risk MDS patients received subcutaneous injection of rhEPO alone or in combination with rhG-CSF at least 8 weeks, the rhEPO dose would be reduced slowly to stop or kept at minimum to maintain the response when the best efficacy achieved and maintained for 4 weeks. Their clinical features, efficacy, survival and the predictors of efficacy were analyzed retrospectively.

RESULTSThe overall response rate was 51.9% (27/52) with 33.3%(9/27) achieving complete remission (CR) and 66.7%(18/27) achieving erythroid response (HI-E). In multivariate analysis, sEPO level (less than 500 U/L), BFU-E count (more than 25/10⁵ BMMNC), intermediate and high doses rhEPO±rhG-CSF therapy were independent predictors of better response. The median therapy period was 8(2-45) months and the median efficacy duration was 37(6-94) months (38 months for CR, 36 months for HI-E). Ten of the 27 responsive patients relapsed and 40% of them had disease progressions. Hemoglobin levels and karyotype affect response duration. Median overall survival was 47(6-114) months on a 37(6-114) months median follow-up. In multivariate analysis, ages (less than 60 years old), karyotype (good or intermediate) and response to rhEPO±rhG-CSF therapy may have a favorable survival impact on MDS.

CONCLUSIONrhEPO, alone or in combination with rhG-CSF, is a useful drug for the treatment of anemia in lower-risk MDS patients and has favorable impact on life expectancy.

Adult ; Aged ; Aged, 80 and over ; Drug Therapy, Combination ; Erythropoietin ; administration & dosage ; therapeutic use ; Female ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; therapeutic use ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes ; therapy ; Recombinant Proteins ; administration & dosage ; therapeutic use ; Retrospective Studies ; Treatment Outcome ; Young Adult

To investigate the efficaciousness of recombinant human granulocyte colony-stimulating factor (G-CSF) combined with recombinant human erythropoietin (EPO) in the treatment of patients with myelodysplastic syndrome (MDS), the hematological changes in the blood and bone marrow along with clinical features after treatment with G-CSF and EPO in 15 patients were observed. Patients were subcutaneously injected with G-CSF 300 microg/d for 10 days, then injected with EPO 100 U/(kg x d) for 10 days. The results showed that the obvious improvements in granulocytes of blood were found in 10 patients with MDS, improvements in erythrocytes of blood were observed in 7 patients with MDS. No serious side effects occured is all treated patients. In conclusion, treatment of G-CSF in combination with EPO is effective for patients with MDS.
Adult ; Aged ; Drug Therapy, Combination ; Erythrocyte Count ; Erythropoietin ; administration & dosage ; adverse effects ; therapeutic use ; Female ; Fever ; chemically induced ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; adverse effects ; therapeutic use ; Headache ; chemically induced ; Humans ; Injections, Subcutaneous ; Leukocyte Count ; Male ; Middle Aged ; Myelodysplastic Syndromes ; drug therapy ; pathology ; Recombinant Proteins ; Treatment Outcome

The protective effect of erythropoietin (EPO) on tissues following ischemia and reperfusion injuries remains poorly understood. We aimed to investigate the effect of EPO in preventing endotoxin-induced organ damage. Rat model of multiple organ failure (MOF) was established by tail vein injection of 10 mg/kg lipopolysaccharide (LPS). Recombinant human EPO treatment (5000 U/kg) was administered by tail vein injection at 30 min after LPS challenge. Twenty-four h after EPO treatment, changes in serum enzyme levels, including aspartate aminotransferase (AST), alanine transaminase (ALT), blood urea nitrogen (BUN) and creatinine (Cr), were evaluated by biochemical analysis. Serum levels of tumor necrosis factor-α (TNF-α) were determined by using immunoradiometric assay. Histological examination of tissue sections was carried out by hematoxylin and eosin staining, while ultrastructure evaluation of organ tissues was assessed by transmission electron microscopy. Protein expression levels were detected by using Western blotting. EPO treatment showed a modest effect in preventing LPS-induced elevation of AST, ALT, BUN, Cr, and TNF-α levels, and in protecting against LPS-induced tissue degeneration and injured ultrastructure in the lung, liver, and kidney. Moreover, LPS promoted phosphorylation of alanine aminotransferase (AKT) and increased nuclear factor-κB (NF-κB) activation in the lung, liver, and kidney (P<0.05 vs. control). However, EPO treatment significantly decreased the LPS-induced pAKT up-regulation in these tissues (P<0.05 vs. LPS treatment alone). The present study demonstrates that EPO may play a protective role against LPS-induced MOF by reducing the inflammatory response and tissue degeneration, possibly via the phosphatidylinositol 3-kinase/AKT and NF-κB signaling pathways.
Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Blood Urea Nitrogen ; Blotting, Western ; Creatinine ; blood ; Endotoxins ; Erythropoietin ; administration & dosage ; genetics ; pharmacology ; Injections, Intravenous ; Kidney ; drug effects ; metabolism ; ultrastructure ; Lipopolysaccharides ; Liver ; drug effects ; metabolism ; ultrastructure ; Lung ; drug effects ; metabolism ; ultrastructure ; Male ; Microscopy, Electron, Transmission ; Multiple Organ Failure ; blood ; chemically induced ; prevention & control ; NF-kappa B ; metabolism ; Phosphorylation ; drug effects ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Rats, Wistar ; Recombinant Proteins ; administration & dosage ; pharmacology ; Tumor Necrosis Factor-alpha ; blood