Comments, concepts and statistics about Haemoglobin Mass and Running Time Trial Performance after Recombinant Human Erythropoietin Administration in Trained Men.
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TY - JOUR. T1 - Erythropoietin administration protects retinal neurons from acute ischemia-reperfusion injury. AU - Junk, Anna. AU - Mammis, Antonios. AU - Savitz, Sean I.. AU - Singh, Manjeet. AU - Roth, Steven. AU - Malhotra, Samit. AU - Rosenbaum, Pearl S.. AU - Cerami, Anthony. AU - Brines, Michael. AU - Rosenbaum, Daniel M.. PY - 2002/8/1. Y1 - 2002/8/1. N2 - Erythropoietin (EPO) plays an important role in the brains response to neuronal injury. Systemic administration of recombinant human EPO (rhEPO) protects neurons from injury after middle cerebral artery occlusion, traumatic brain injury, neuroinflammation, and excitotoxicity. Protection is in part mediated by antiapoptotic mechanisms. We conducted parallel studies of rhEPO in a model of transient global retinal ischemia induced by raising intraocular pressure, which is a clinically relevant model for retinal diseases. We observed abundant expression of EPO receptor (EPO-R) throughout the ischemic retina. Neutralization of endogenous ...
he National Anemia Action Council states that about 3.4 million Americans are anemic, with causes ranging from serious chronic illnesses to simple dietary insufficiencies (1). Common symptoms include weakness, pallor, tachycardia, shortness of breath, dizziness, headache, chest pain, and numbness in the extremities (1). Since the late 1990s, recombinant erythropoietin has been used to treat anemic patients, including cancer patients whose anemia has been caused by chemotherapy (2).. Recombinant erythropoietin is also known as epoetin alfa, or EPO, a glycoprotein made by transplanting the human erythropoietin gene into the ovary cells of a Chinese hamster species (2). Due to its relative novelty in the research community, older and newer studies are very similar in their findings that erythropoietin effectively raises hemoglobin levels in anemic patients. Current research, however, is focused on quantifying hemoglobin concentration increases from erythropoietin treatment, exploring possible ...
Aim: The purpose of the present study was to evaluate the normobaric oxygen paradox theory by investigating the effect of a 2-h normobaric O(2) exposure on the concentration of plasma erythropoietin (EPO). Methods: Ten healthy males were studied twice in a single-blinded counterbalanced crossover study protocol. On one occasion they breathed air (NOR) and on the other 100% normobaric O(2) (HYPER). Blood samples were collected Pre, Mid and Post exposure; and thereafter, 3, 5, 8, 24, 32, 48, 72 and 96 h, and 1 and 2 weeks after the exposure to determine EPO concentration. Results: The concentration of plasma erythropoietin increased markedly 8 and 32 h after the NOR exposure (approx. 58% and approx. 52%, respectively, P , 0.05) as a consequence of its natural diurnal variation. Conversely, the O(2) breathing was followed by approx. 36% decrement of EPO 3 h after the exposure (P , 0.05). Moreover, EPO concentration was significantly lower in HYPER than in the NOR condition 3, 5 and 8 h after the ...
The effect of post-injury erythropoietin administration on mortality and Glasgow outcome scales of patients with traumatic brain injury: A metaanalysis., Faye B Garciano, Perry N N
Recombinant human erythropoietin (EPO), given intravenously, or even better, subcutaneously, represents a major advance in treating patients with end-stage renal failure. It has been studied most frequently in patients on hemodialysis and has been shown to increase hemoglobin levels, improve quality of life, and permit avoidance of transfusion with its concomitant risk of infection, iron overload, and sensitization (1). The major side effects of the medication have been hypertension and flu-like symptoms. Subcutaneous EPO can be self-administered and may require a lower dose than intravenous EPO (unfortunately, the mean maintenance dose of erythropoietin in this study was not indicated). The authors found no difference in hypertension between the 2 groups, and no unexpected side effects were reported. There has been concern that the increase in hematocrit in predialysis patients treated with EPO may be associated with acceleration of renal failure. Other studies have found no change in the ...
Erythropoietin (Epo), a 30.4-kD glycoprotein, is the principal regulator of erythropoiesis. To evaluate the concept that in vivo gene transfer might be used as an alternative to recombinant human Epo (rhEpo) in applications requiring a 1- to 3-week stimulation of erythropoiesis, the replication-deficient recombinant adenovirus AdMLP.Epo was constructed by deleting the majority of E1 from adenovirus type 5, and replacing E1 with an expression cassette containing the adenovirus type 5 major late promoter (MLP) and the human Epo gene, including the 32 cis-acting hypoxia response element. In vitro studies showed that infection of the human hepatocyte cell line Hep3B with AdMLP.Epo resulted in a 15-fold increase in Epo production in 24 hours that was enhanced to 116-fold in the presence of a hypoxic stimulus. One-time in vivo administration of AdMLP.Epo (7 x 10(9) plaque-forming units/kg) to the peritoneum of cotton rats caused a marked increase in red blood cell production, with a 2.6-fold increase ...
The expression system was used to create recombinant human erythropoietin, a protein synthesized by the adult kidney and responsible for the regulation of red blood cell production. of recombinant EPO and increase the activity of TG-101348 this protein Yeasts have long been a model organism for biochemical and genetic studies because of the advantages they offer compared to bacterial systems, including the ease with which they can cultured and managed, and the fact that they share several important biological characteristics with eukaryotic cells, such as splicing and other processes involved in post-translational modifications. Several yeast species have been used to generate recombinant proteins, including and (examined in B?er offers similar advantages to other yeasts, and are preferred as the overall length of the mannose outer chains is shorter than in (Kang and construction of the gene The entire human erythropoietin gene was constructed using the Splicing by Overlap-Extension by PCR ...
Background Our original demonstration of immunomodulatory effects of erythropoietin in multiple myeloma, led us to the search of the cells in the immune system that are direct targets to erythropoietin. The finding that lymphocytes do not express erythropoietin receptors, has led to the hypothesis that other cells act as direct targets and thus mediate the erythropoietin effects. Having found erythropoietin effects on dendritic cells thus led to the question of whether macrophages act as target cells to erythropoietin. Design and Methods EPO effects on macrophages were investigated both in-vivo and in-vitro. The in-vivo studies were performed on splenic macrophages and inflammatory peritoneal macrophages, in recombinant human erythropoietin -treated, compared to untreated mice, as well as in transgenic mice over-expressing human erythropoietin (tg6), compared to their control wild type counterparts. The in-vitro effects of erythropoietin on macrophage surface markers and function were ...
1. Wu H, Liu X, Jaenisch R, Lodish HF. Generation of committed erythroid BFU-E and CFU-E progenitors does not require erythropoietin or the erythropoietin receptor. Cell. 1995;83:59-67 2. Miyake T, Kung CK, Goldwasser E. Purification of human erythropoietin. The Journal of biological chemistry. 1977;252:5558-64 3. Lin FK, Suggs S, Lin CH, Browne JK, Smalling R, Egrie JC. et al. Cloning and expression of the human erythropoietin gene. Proceedings of the National Academy of Sciences of the United States of America. 1985;82:7580-4 4. Jacobs K, Shoemaker C, Rudersdorf R, Neill SD, Kaufman RJ, Mufson A. et al. Isolation and characterization of genomic and cDNA clones of human erythropoietin. Nature. 1985;313:806-10 5. Noguchi CT, Wang L, Rogers HM, Teng R, Jia Y. Survival and proliferative roles of erythropoietin beyond the erythroid lineage. Expert reviews in molecular medicine. 2008;10:e36. doi:10.1017/S1462399408000860 6. Teng R, Gavrilova O, Suzuki N, Chanturiya T, Schimel D, Hugendubler L. et ...
Study Objective: To determine the efficacy and safety of recombinant human erythropoietin (r-HuEPO) in predialysis renal patients.. Design: Randomized, double-blind, placebo-controlled trial for 8 weeks.. Setting: Inpatient and outpatient facility in the Clinical Research Center of a university-based hospital.. Patients: Fourteen adult subjects with renal insufficiency (mean serum creatinine, 473 µmol/L ± 61 [6.2 µ 0.8 mg/dL] ) and anemia (mean hematocrit, 0.27 ± 0.01).. Interventions: Recombinant human erythropoietin, 50, 100, or 150 IU/kg body weight or placebo given intravenously three times per week.. Measurements and Main Results: Subjects who received active r-HuEPO showed a dose-dependent rise in hematocrit; mean hematocrit increased 41% from 0. 27 ± 0.01 to 0.38 ± 0.01. At the same time, erythrocyte mass rose 43% from 13.7 ± 0.6 mL/kg in the baseline state to 19.6 ± 1.0 mL/kg after treatment. Maximal oxygen consumption during exercise increased 9% from 16.0 mL/min · kg ± 1.8 to ...
A. A male patient with JAK2 V617F mutation, hemoglobin of 13.5 g/dL, and subnormal serum erythropoietin level. B. A male patient with JAK2 V617F mutation, hemoglobin of 16.5 g/dL, and subnormal serum erythropoietin level. C. A patient with JAK2 V617F mutation, hemoglobin of 18.5 g/dL, and subnormal serum erythropoietin level. D. A and B are correct. Question 2 Which of the following is a minor criterion to facilitate the diagnosis of polycythemia vera?. A. Elevated hematocrit of , 48% in women and , 49% in men. B. Elevated hemoglobin of , 16.0 g/dL in women and , 16.5 g/dL in men. C. Bone marrow biopsy showing age-adjusted hypercellularity with panmyelosis and pleomorphic mature megakaryocytes. D. Subnormal serum erythropoietin level. Question 3 Which of the following is a well-described bone marrow characteristic of polycythemia vera?. A. Unilineage erythroid hyperplasia. B. Age-adjusted hypercellularity. C. Pleomorphic immature megakaryocytes. D. All of the above. Question 4 Which of the ...
A. A male patient with JAK2 V617F mutation, hemoglobin of 13.5 g/dL, and subnormal serum erythropoietin level. B. A male patient with JAK2 V617F mutation, hemoglobin of 16.5 g/dL, and subnormal serum erythropoietin level. C. A patient with JAK2 V617F mutation, hemoglobin of 18.5 g/dL, and subnormal serum erythropoietin level. D. A and B are correct. Question 2 Which of the following is a minor criterion to facilitate the diagnosis of polycythemia vera?. A. Elevated hematocrit of , 48% in women and , 49% in men. B. Elevated hemoglobin of , 16.0 g/dL in women and , 16.5 g/dL in men. C. Bone marrow biopsy showing age-adjusted hypercellularity with panmyelosis and pleomorphic mature megakaryocytes. D. Subnormal serum erythropoietin level. Question 3 Which of the following is a well-described bone marrow characteristic of polycythemia vera?. A. Unilineage erythroid hyperplasia. B. Age-adjusted hypercellularity. C. Pleomorphic immature megakaryocytes. D. All of the above. Question 4 Which of the ...
Animal Model. Neonatal Wistar rats were randomly divided into three groups: 1) no-stroke control, 2) saline control, and 3) rhEPO treatment. The surgical procedure of whisker-barrel cortex ischemia in neonatal rats followed similar methods as described previously (Wei et al., 2006). In brief, postnatal day 7 (P7) pups were anesthetized by hypothermia. Hypothermia anesthesia was chosen because many of the drugs used to anesthetize adult animals provided inadequate anesthesia for neonates or were associated with problems such as excessively high mortality (Danneman and Mandrell, 1997). In this regard, hypothermia (immersion in ice) has been judged as a humane, safe, and effective anesthesia method for survival surgeries of neonatal rats (Danneman and Mandrell, 1997). The hypothermia procedure was kept the same for all pups in different experimental groups. Pups were placed in a noninvasive head-holder to allow for a 2.5- to 3.0-mm-diameter craniectomy through the right parietal skull. The ...
TY - JOUR. T1 - Recombinant human erythropoietin for chronic renal failure anaemia in pre-dialysis patients. AU - Cody, June D. AU - Daly, Conal. AU - Campbell, Marion K. AU - Khan, Izhar. AU - Rabindranath, Kannaiyan S. AU - Vale, Luke. AU - Wallace, Sheila A. AU - MacLeod, Alison M. AU - Grant, Adrian M. AU - Pennington, Susan AU - Nistor, Ionut. AU - Bolignano, Davide. AU - Webster, Angela C. PY - 2005/7/20. Y1 - 2005/7/20. N2 - Background Treatment with recombinant human erythropoietin (rHu EPO) in dialysis patients has been shown to be highly effective in terms of correcting anaemia and improving quality of life. There is debate concerning the benefits of rHu EPO use in pre-dialysis patients which may accelerate the deterioration of renal function. However the opposing view is that if rHu EPO is as effective in pre-dialysis patients, improving the patients sense of well-being may result in the onset of dialysis being delayed.Objectives To assess the effects of rHu EPO use in pre-dialysis ...
Cellular and molecular mechanisms regulating the hepatic erythropoietin expression during acute-phase response: a role for IL-6 Ramadori P, Ahmad G, Ramadori G. Source Department of Gastroenterology and Endocrinology, Center of Internal Medicine, University of Göttingen, Göttingen, Germany. Abstract The source of circulating erythropoietin (EPO), the mediators and the mechanisms involved in the upregulation of EPO…
Erythropoietin is an essential growth factor that promotes survival, proliferation, and differentiation of mammalian erythroid progenitor cells. Erythropoietin(−/−) and erythropoietin receptor(−/−) mouse embryos die around embryonic day 13.5 due, in part, to failure of erythropoiesis in the fetal liver. In this study, we demonstrated a novel role of erythropoietin and erythropoietin receptor in cardiac development in vivo. We found that erythropoietin receptor is expressed in the developing murine heart in a temporal and cell type-specific manner: it is initially detected by embryonic day 10.5 and persists until day 14.5. Both erythropoietin(−/−) and erythropoietin receptor(−/−) embryos suffered from ventricular hypoplasia at day 12-13 of gestation. This defect appears to be independent from the general state of hypoxia and is likely due to a reduction in the number of proliferating cardiac myocytes in the ventricular myocardium. Cell proliferation assays revealed that ...
Effects of theophylline on erythropoietin production in normal subjects in patients with erythrocytosis after renal transplantation
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We have used RNase protection to measure oxygen-dependent changes in erythropoietin (EPO) mRNA in isolated perfused kidneys and to compare the effect of hypoxia with the response to inhibitors of oxidative phosphorylation. In well-oxygenated kidneys perfused for 2 h at 12 ml/min, with hematocrit of 0.09 +/- 0.005 and PO2 of 443 +/- 67 mmHg, EPO mRNA levels were similar to the baseline levels measured in nonperfused contralateral kidneys from the same animals. When perfusions were performed under identical conditions but at a PO2 of 32 +/- 4 mmHg, EPO mRNA increased approximately 16-fold. In contrast, graded concentrations of cyanide (10, 100, and 300 microM and 1 mM), antimycin (0.01, 0.1, 0.5, and 1 microM), and oligomycin (0.01, 0.1, and 1 microM) did not alter EPO mRNA in well-oxygenated perfused kidneys. However, in kidneys perfused at low PO2 with a high concentration of each inhibitor, EPO mRNA levels were increased, demonstrating that the ability to respond to hypoxia was retained. Thus
Background: Ischemia/reperfusion (I/R) injury is an important cause of renal graft dysfunction. Increases in cold and warm ischemia times lead to a higher risk of early posttransplant complications including delayed graft function and acute rejection. Moreover, prolonged cold ischemia is a predictor of long-term graft loss in kidney transplant patients. Methods: Darbepoetin alfa (DA) and carbamylated nonerythropoietic derivative of erythropoietin (CEPO) protective effects were evaluated in a model of I/R injury after kidney transplantation in both syngeneic and allogeneic combinations. The effects of wortmannin (phosphorylated Akt [p-Akt] inhibitor) administration were also investigated. Serum creatinine was evaluated at 16, 24, 48 hr and at 4 and 7 days posttransplant. Animals were killed 24 hr or 7 days after transplant and kidneys were processed for histological analysis, immunohistochemistry assessment of erythropoietin receptor (EPOR) and β-common chain receptor expression, granulocyte ...
Michael, A, Politi, E, Havranek, E, Corbishley, C, Karapanagiotou, L, Anderson, C, Relph, K, Syrigos, KN and Pandha, H (2007) Prognostic significance of erythropoietin expression in human renal cell carcinoma ...
Experiments were performed to test the hypothesis that rats could be made permanently anemic by repeated mixed gamma-neutron irradiations, and that once the maintenance of normal circulatory red cell concentration was lost, the administration of exogenous erythropoietin could not restore the production of red cells to normal levels. Rats were exposed to 9 periodic doses of 150 rads mixed gamma-neutron radiation or to 4 periodic doses of 300 rads. Hematocrits and erythrocyte counts obtained for 100 days or more after the final radiation exposure showed a significant reduction in erythrocyte production. This permanent anemia was not ameliorated by the treatment with 5 daily doses of either 5 units or 25 units of erythropoietin. These findings appear to strengthen the hypothesis that the permanent anemia is caused by a reduced capability for cellular proliferation due to accumulation of residual injury in stem cells.
Although rhEPO treatment is beneficial for CKD patients with renal anemia, several problems remain to be addressed. First, the increasing number of CKD patients is expanding the demand for rhEPO treatment, which, in turn, increases the total cost of this therapy. Second, it is difficult to physiologically control renal anemia using rhEPO treatment. The intermittent administration of rhEPO causes fluctuations in hemoglobin concentrations (3), which is associated with an increased incidence of cardiovascular events (23). In addition, the target hemoglobin concentration for rhEPO treatment remains controversial, and hemoglobin concentrations in most patients are lower than those observed in healthy subjects (24). The physiological control of renal anemia based on a stable, normal range of hemoglobin concentrations may help in the treatment of CKD patients.. hiPSCs/ESCs are potential cell sources for regenerative medicine. Here, we generated EPO-producing cells from hiPSCs/ESCs and miPSCs/ESCs. ...
The present invention provides an expression system for producing recombinant human erythropoietin (rhEPO) exhibiting biological activity and immunochemical properties of the native human erythropoietin (hEPO). Also provided is an improved method for purifying rhEPO from culture medium by two-step column chromatography.
BACKGROUND: Preclinical studies and pilot clinical trials have shown that high-dose erythropoietin (EPO) reduces infarct size in acute myocardial infarction. We investigated whether a single high-dose of EPO administered immediately after reperfusion in patients with ST-segment elevation myocardial infarction (STEMI) would limit infarct size. METHODS: A total of 110 patients undergoing successful primary coronary intervention for a first STEMI was randomized to receive standard care either alone (n = 57) or combined with intravenous administration of 1,000 U/kg of epoetin β immediately after reperfusion (n = 53). The primary end point was infarct size assessed by gadolinium-enhanced cardiac magnetic resonance after 3 months. Secondary end points included left ventricular (LV) volume and function at 5-day and 3-month follow-up, incidence of microvascular obstruction (MVO), and safety. RESULTS: Erythropoietin significantly decreased the incidence of MVO (43.4% vs 65.3% in the control group, P = .03) and
The membrane-assisted isoform immunoassay (MAIIA) quantitates erythropoietin (EPO) isoforms as percentages of migrated isoforms (PMI). We evaluated the effect of recombinant human EPO (rhEPO) on the distribution of EPO isoforms in plasma in a randomized, placebo-controlled, double-blinded, cross-over study. 16 healthy subjects received either low-dose Epoetin beta (5000 IU on days 1, 3, 5, 7, 9, 11 and 13); high-dose Epoetin beta (30.000 IU on days 1, 2 and 3 and placebo on days 5, 7, 9, 11 and 13); or placebo on all days. PMI on days 4, 11 and 25 was determined by interaction of N-acetyl glucosamine with the glycosylation dependent desorption of EPO isoforms. At day 25, plasma-EPO in both rhEPO groups had returned to values not different from the placebo group. PMI with placebo, reflecting the endogenous EPO isoforms, averaged 82.5 (10.3) % (mean (SD)). High-dose Epoetin beta decreased PMI on days 4 and 11 to 31.0 (4.2)% (p,0.00001) and 45.2 (7.3)% (p,0.00001). Low-dose Epoetin beta decreased ...
TY - JOUR. T1 - Clinical validation of an RIA for natural and recombinant erythropoietin in serun and plasma. AU - Goldberg, Mark A.. AU - Schneider, Thomas J.. AU - Khan, Shaista. AU - Petersen, John R.. PY - 1993. Y1 - 1993. N2 - A sensitive radioimmunoassay (RIA) for the detection of erythropoietin (EPO) was developed using antibody directed against EPO from human urine. With 100 μL of sample, the assay is sensitive to 7 U/L, well below the mean EPO level in normal males (15.1 ± 3.5 U/L) or females (15.4 ± 4.8 U/L). Dilutions of a variety of human serum samples show a parallel relationship with the standard EPO. Clinical validation of the RIA was confirmed by appropriate increases or decreases of EPO levels in various types of anemia and polycythemia. Serum EPO levels were also measured in volunteers participating in an autologous blood donation study. The RIA proved to eb quite sensitve, detecting small increases even after a single unit phlebotomy. This RIA of human EPO meets all the ...
METHODS: Thirty-five rats were divided into 3 groups. In the baseline control group (BC, n=7), rats were uninjured and untreated. In the positive control group (PC, n=21) rats were injured but untreated. In the EPO-24 group (n=7), rats were injured and a single dose of intra-peritoneal EPO (5000 IU/kg) was administered immediately after lung injury. The PC group was divided into 3 subgroups: PC-6 (n=7), PC-12 (n=7), and PC-24 (n=7). The BC group was subjected to thoracotomy, and the right lung was harvested. The PC subgroups were eu-thanized at 6, 12, and 24 hours after injury, respectively. The EPO-24 group was euthanized at the 24th hour after injury. Lung samples were obtained, levels of malondialdehyde (MDA) and EPO were analyzed, and activities of superoxide dismutase (SOD) and catalase (CAT) were then measured in homogenized lung tissue samples. Histologic damage to lung tissue in the BC group, the EPO-24 group, and PC subgroup euthanized at the 24th hour after injury were scored by a ...
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TY - JOUR. T1 - Erythropoietin fails to reverse the anemia in mice continuously exposed to tumor necrosis factor-alpha in vivo. AU - Clibon, U.. AU - Bonewald, Lynda. AU - Caro, J.. AU - Roodman, G. David. PY - 1990. Y1 - 1990. N2 - Tumor necrosis factor-α (TNF) is a monokine produced by activated macrophages that has cytotoxic and cytostatic effects on erythroid progenitor cells. We have recently shown that Chinese hamster ovary cells transfected with the human TNF gene and which constitutively express TNF induced a hypoproliferative anemia, mild thrombocytopenia, and mild leukocytosis when injected into nude mice. We have used this murine model to determine if treatment with recombinant human erythropoietin can prevent or ameliorate the anemia seen with long-term continuous exposure to high concentrations of TNF. Mice bearing TNF-producing tumors became anemic with hematocrits ranging from 30 to 32%. Treatment with recombinant human erythropoietin (100-1000 U/kg body weight three times per ...
RATIONALE: Darbepoetin alfa and epoetin alfa may stimulate red blood cell production and treat anemia in patients who are receiving chemotherapy. It is not yet known whether darbepoetin alfa is more effective than epoetin alfa in treating patients with anemia.. PURPOSE: Randomized phase III trial to compare the effectiveness of darbepoetin alfa with that of epoetin alfa in treating anemia in patients who are receiving chemotherapy for cancer. ...
Erythropoietin is a substance produced by the kidney that leads to the formation of red blood cells in the bone marrow. It is a glycoprotein hormone which regulates erythropoiesis (Red Blood Cell production). For erythrocyte precursors present in the bone marrow, EPO acts as a cytokine. Commonly referred to as hematopoietin or hemopoietin, erythropoietin is also known to have other biological functions, such as involvement in the wound healing cycle and brains response to neuronal injury. People suffering from End Stage Renal Disease (ESRD), HIV or undergoing chemotherapy are not able to produce enough EPO on their own and thus, are administered with synthetic or recombinant erythropoietin which has the similar sequence of amino acids. Recombinant erythropoietin is a kind of therapeutic agent devised using DNA technology.. Request a sample of this report at http://www.orbisresearch.com/contacts/request-sample/127811 .. On the bases of their molecular structure, EPO drugs can be divided into ...
Using the human hepatoma cell line Hep G2, we have studied a possible role of protein kinase C (PKC) activity for regulation of erythropoietin (EPO) production. During a 72-h incubation, EPO production by the cells was stimulated sevenfold by exposure to low oxygen tension (1%) and threefold by exposure to cobaltous chloride (100 microM). The phorbol ester phorbol 12-myristate-13 acetate (PMA) led to a concentration-dependent inhibition of basal and stimulated EPO formation (ED50 10 nM). This decrease of EPO production, which was apparent already after 1 h of incubation with PMA, reached its maximal effect after 24 h and held on for 72 h. It was paralleled by an inhibition of the increase of EPO mRNA levels in response to stimulation. A 24-h preincubation of the cells with PMA (100 nM) virtually blunted the effect of hypoxia on EPO formation. Recovery of EPO synthesis after removal of PMA took 48-72 h. The effect of PMA on EPO production was mimicked by phorbol 12,13-dibutyrate (ED50 1 microM) but not
Chemotherapy can often cause anemia in patients with cancer. Anemia is a low number of red blood cells. The symptoms of anemia may include fatigue, dizziness, headache, chest pain, and shortness of breath. Erythropoietin is a hormone made by the kidneys that signals the bone marrow to produce more red blood cells. Recombinant human erythropoietin has been produced in the laboratory and has the same effect as the hormone produced by the body. Use of recombinant human erythropoietin allows the body to produce more red blood cells, possibly eliminating or decreasing your symptoms and the need for a red blood cell transfusion. Recombinant human erythropoietin is FDA approved to treat anemia in cancer patients receiving chemotherapy. This clinical study is investigating the effectiveness of darbepoetin alfa for the treatment of anemia in patients with non-myeloid malignancies who are receiving chemotherapy every three weeks. Darbepoetin alfa is a recombinant erythropoietic protein that stimulates the ...
|i|Objectives:|/i| Platinum compounds are commonly associated with significant anemia. Erythropoietin administration has been found effective in correcting anemia in patients with solid tu
Background: Recombinant human erythropoietin (rhEPO) protects tissue from ischemic damage, but translation of this finding into useful guidelines with respect to human trials for myocardial infarction
View Notes - Week_9_Pre-Discussion_Assignment from CHEMISTRY Chem 1LB at UC Irvine. Erythropoietin The human growth hormone erythropoietin (EPO) is secreted primarily by the kidneys. It binds to
High-dose (40,000 IU twice/week) alpha recombinant human erythropoietin as single agent in low/intermediate risk myelodysplastic syndromes: a retrospective investigation on 133 patients treated in a single institution. - Antonio Azzarà, Giovanni Carulli, Sara Galimberti, Claudia Baratè, Rita Fazzi, Giulia Cervetti, Mario Petrini
Considerable insights into important cis regulatory elements in a gene can be gleaned from the identification of sequence homologies among different species. To extend and optimize the sequence comparison between human and mouse erythropoietin (Epo) genes, we have obtained new human sequence from 5,547 to 385 bp upstream of the cap site and extended the 3 flank by 489 bp. In addition, we have obtained new sequence information on the mouse Epo gene extending from within the 3 untranslated region (UTR) to 1,001 bp downstream of the polyadenylation site. Analysis of these additional sequences shows considerable homology between human and mouse Epo genes as far as 4 kb (human) or 3 kb (mouse) upstream of the cap sites, as well as far more homology at the 3 end than was previously realized. In addition, both species were found to have a high frequency of short interspersed (SINE) repetitive sequences that interrupt homologies in both the 5 flank and within the transcription unit.
The N-linked carbohydrate chains of recombinant human erythropoietin expressed in CHO cells were quantitatively released with peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase F, separated from the remaining O-glycoprotein by gel-permeation chromatography, and subsequently fractionated via FPLC on Mono Q, HPLC on Lichrosorb-NH2 and high-pH anion-exchange chromatography on CarboPac PA1. The purified sialylated oligosaccharides were ... read more analyzed by one-dimensional and two-dimensional 500-MHz 1H-NMR spectroscopy. When necessary, oligosaccharides were treated with endo-beta-galactosidase (and N-acetyl-beta-glucosaminidase) followed by 1H-NMR analysis of the incubation products, to obtain additional structural information. Di-, tri-, tri- and tetraantennary, N-acetyllactosamine-type oligosaccharides occur which can be completely (major) or partially (minor) sialylated. Three different types of alpha2-3-linked sialic acids are present, namely, N-acetylneuraminic acid (95%), ...
Administration of recombinant human erythropoietin in patients with gynecological cancer before radical surgery. - V Dousias, T Stefos, I Navrozoglou, I Staikos, A Ditto, E Paraskevaidis
High quality EPO/Recombinant Human Erythropoietin Injection(CHO Cell) Contact info: e-mail:[email protected] skype:live:sunnylidi whatsapp:+8613735524230 http://www.holyuniverse-pharm.com Introduction Modified GRF 1-29(Cjc1295) and...
The identification of amino acid residues essential for function of the hematopoietic growth factor erythropoietin has been approached by several methods, including comparisons of related sequences, immunochemical approaches, mutagenesis and computer modeling. We have reported previously that mutations within amino acids 100-109 of erythropoietin can have profound effects on the hormones structure and/or activity and that Arg103 is especially important for function (Chern, Y., Chung, T. & Sytkowski, A.J. (1991) Eur. J: Biochem. 202, 225-229; Grodberg, J. Davis, K. L. & Sytkowski, A. J. (1993) Eur. J Biochem. (218, 597-601). We have now constructed a series of Arg 103 substitutions in order to determine the structural features of amino acid 103 required for biological activity. Each of the mutants was expressed and secreted efficiently by transfected COS1 cells. Mutants Arg103Asn, Arg103Gln, Arg103CGlu exhibited no biological activity. In contrast, Arg103His and Arg103Lys had specific activities equal
Carbamylerythropoietin (CEPO) does not bind to the classical erythropoietin (EPO) receptor. Nevertheless, similarly to EPO, CEPO promotes neuroprotection on the histologic level in short-term stroke models. In the present study, we investigated whether CEPO and other nonerythropoietic EPO analogs could enhance functional recovery and promote long-term histologic protection after experimental focal cerebral ischemia. Rats were treated with the compounds after focal cerebral ischemia. Animals survived 1, 7, or 60 days and underwent behavioral testing (sensorimotor and foot-fault tests). Brain sections were stained and analyzed for Iba-1, myeloperoxidase, Tau-1, CD68 (ED1), glial fibrillary acidic protein (GFAP), Fluoro-Jade B staining, and overall infarct volumes. Treatment with CEPO reduced perifocal microglial activation (P, 0.05), polymorphomonuclear cell infiltration (P, 0.05), and white matter damage (P , 0.01) at 1 day after occlusion. Carbamylerythropoietin- treated rats showed better ...
... , or its alternativeerythropoetin orEPO, is a glycoprotein hormone that controls erythropoiesis, or red blood cell production. It is a cytokine for erythrocyte (red blood cell) precursors in the bone marrow. Also calledhematopoietin orhemopoietin, it is produced by the peritubular capillary endothelial cells in the kidney, and is the hormone that regulates red blood cell production. It also has other known biological functions. For example, erythropoietin plays an important role in the brain`s response to neuronal injury. EPO is also involved in the wound healing process. When exogenous EPO is used as a performance-enhancing drug, it is classified as an erythropoiesis-stimulating agent (ESA). Exogenous EPO can often be detected in blood, due to slight difference from the endogenous protein, for example in features of posttranslational modification. History In 1906, Paul Carnot, a professor of medicine in Paris, and his assistant DeFlandre proposed the idea that hormones regulate ...
We recently determined that erythropoietin (EPO) activates 3 members of the signal transducer and activator of transcription (STAT) family, Stat1α, Stat3, and Stat5, in the human EPO-dependent cell lines, UT-7 and UT-7/EPO (Kirito et al, J Biol Chem 272:16507, 1997). In addition, we have shown that Stat1α, but not Stat3, is involved in EPO-induced cellular proliferation. In this study, we examined the roles of Stat1α and Stat3 in EPO-induced erythroid differentiation. UT-7/GM was used as a model system, because this cell line can differentiate into erythroid-lineage cells with EPO treatment (Komatsu et al, Blood 89:4021, 1997). We found that EPO did not activate Stat1α or Stat3 in UT-7/GM cells. Transfection experiments showed that both Stat1α and Stat3 inhibited the induction by EPO of γ-globin and erythroid-specific 5-aminolevulinate synthetase transcripts, resulting in a reduction of the percentage of hemoglobin-positive cells. Dominant negative forms of Stat1α or Stat3 promoted the ...
Allogeneic cells are the most attractive source for cell transplantation, as the use of xenogeneic cells is hampered by safety concerns and the use of autologous cells involves practical difficulties. The immune rejection of allogeneic cells can be overcome by physical immunoprotection provided by polymer encapsulation. To study the variability of cell and donor sources, we compared different primary human cells as candidates for gene therapy-mediated delivery of human erythropoietin (hEpo). DARC-3.1 fibroblasts, MDX-01 fibroblasts, and ARPE-19 retinal pigment epithelial cells were encapsulated into polyethersulfone hollow fibers and implanted for 1 month in nude mice as well as in immunocompetent and FK506-immunosuppressed mice to test their in vivo resistance, with the assumption that xenogeneic conditions constitute a stringent model for human application. DARC-3.1 fibroblasts showed the best survival, prompting us to evaluate cell lineages from the same donor (DARC-3.2) or another donor (DARC-4.3
Title: Erythropoietin: New Approaches to Improved Molecular Designs and Therapeutic Alternatives. VOLUME: 14 ISSUE: 13. Author(s):N. Debeljak and A. J. Sytkowski. Affiliation:Laboratory for Cell and Molecular Biology, Division of Hematology and Oncology, Beth Israel Deaconess Medical Center, Department of Medicine, Harvard Medical School,330 Brookline Ave., W/BL 548, Boston, MA 02215, USA.. Keywords:Erythropoietin, erythropoietin receptor, glycosylation, pegylation, fusion proteins, mimetics, heteroreceptor, cancer. Abstract: Erythropoietin (Epo) is a glycoprotein hormone that is the prime regulator of erythropoiesis. Recombinant Epo is a highly effective pharmaceutical used to correct anemias associated with renal insufficiency, cancer and other diseases. Efforts to increase its efficacy in vivo by manipulating the proteins structure have met with some success, and novel Epo-like agents are in development. Additionally, efforts to create Epo mimetic agents are underway, as is the design of ...