epoetin-alfa and Hypoxia

Anemia persists as a challenge in chronic kidney disease (CKD) patients. Current therapies are the injectable erythropoietin stimulating agents (ESA). Concerns have been raised regarding ESA cardiovascular safety, therefore search for an alternative, convenient and safe therapy is underway. Hypoxia inducible factors-prolyl hydroxylase inhibitors (HIF-PHI) are oral agents with promising results. Numerous small studies reported favorable effects with lack of large, powered studies.. We conducted a meta-analysis of randomized clinical trials to assess the efficacy and safety of HIF-PHI in non-dialysis-dependent CKD patients. Primary outcome was hemoglobin (Hb) concentration post intervention. Secondary outcomes were all-cause mortality, MACE, and changes in iron metabolism (ferritin, hepcidin). We reported total and serious adverse effects. Data were pooled using a random effect model via RevMan 5.4 software.. We identified 7 trials comprising of 8228 patients (mean age 66.5 ± 13.2 years, 42% were females, 53% used iron replacement) with a mean follow-up of 52 weeks. Compared with the standard of care (ESA), HIF-PHI were non-inferior for treatment of anemia, with comparable effect on mortality and major adverse cardiovascular events. HIF-PHI showed no major safety concerns. Main side effect of HIF-PHI was diarrhea.. HIF-PHI might represent a safe, and convenient alternative to ESA in non-dialysis dependent CKD patients with anemia.

Topics: Aged; Anemia; Epoetin Alfa; Female; Humans; Hypoxia; Iron; Male; Middle Aged; Prolyl Hydroxylases; Prolyl-Hydroxylase Inhibitors; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic

Renal anemia, a common complication and threat factor of chronic kidney disease (CKD), has long been treated with injectable erythropoietin-stimulating agents (ESAs). As concerns regarding cardiovascular safety and erythropoietin resistance to ESAs have emerged, alternative therapies are urgently needed. Hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), an oral agent, has been proven to be effective in improving renal anemia. However, the effects of HIF-PHIs on nondialysis-dependent CKD (NDD-CKD) have yet to be supported by updated meta-analyses.. A meta-analysis of clinical randomized controlled trials (RCTs) on HIF-PHI treatment of NDD-CKD patients based on PubMed, EMBASE, and Cochrane databases as of July 16th, 2023, was conducted. The primary outcomes were the level of hemoglobin (Hb) postintervention and the ratio of Hb responses. Most of the analysis was conducted. Twenty-two studies with a total of 7178 subjects in the HIF-PHI group, 3501 subjects in the ESA group and 2533 subjects in the placebo group were enrolled. HIF-PHIs increased the level of Hb and improved iron metabolism but were not inferior to ESAs in terms of safety.. HIF-PHIs may be a convenient and safe alternative to ESAs in patients with NDD-CKD and anemia.

Topics: Anemia; Epoetin Alfa; Erythropoietin; Humans; Hypoxia; Prolyl Hydroxylases; Prolyl-Hydroxylase Inhibitors; Renal Insufficiency, Chronic

Although we have known since the 19th century that oxygen tension affects erythrocyte production, we have only recently begun to understand many subtleties of erythropoietin physiology. The unanticipated increase in mortality associated with erythropoietin use found in recent randomized studies is prompting a reassessment of static hemoglobin targets. Hemoglobin levels in dialysis patients do not correlate with endogenous erythropoietin production and may be related to differences in oxygen delivery resulting from shifts in the oxygen-hemoglobin dissociation curve. The time may have arrived to develop more physiologic targets such as oxygen delivery that would mimic the natural response to hypoxia. There are several equations that already exist that can compensate for the effects of the concentration of inorganic and organic phosphates as well as pH, carbon dioxide, and temperature on the delivery of oxygen. However, since the shape and dispersion of the oxygen-hemoglobin dissociation curve may actually change in different disease states, more work is needed.

Topics: Algorithms; Blood Transfusion; Carbon Dioxide; Epoetin Alfa; Erythropoiesis; Erythropoietin; Feedback, Physiological; Hemoglobins; Humans; Hydrogen-Ion Concentration; Hypoxia; Hypoxia-Inducible Factor 1; Models, Biological; Oxygen; Oxyhemoglobins; Patient Care Planning; Phosphates; Randomized Controlled Trials as Topic; Recombinant Proteins

Multiple myeloma (MM) is commonly associated with anemia. Several causes have been implicated, but anemia of chronic disease with inadequate erythropoietin (EPO) production related to the inflammatory cytokines appears to be of utmost importance. Interleukin-1 and tumor necrosis factor are capable of suppressing erythropoiesis. Anemia has broad implications. First, the low hemoglobin and hematocrit are associated with poor quality of life and performance and affect daily activity. Second, anemia has an impact on the cardiovascular system. Considering that most MM patients are elderly, this may be even more important. Anemia has been shown to induce or aggravate hypoxia and ischemic complications. Third, anemia has been shown to be a poor prognostic factor in MM. Traditionally, patients with symptomatic anemia were treated with red blood cell transfusions as needed. The introduction of epoetin alfa and epoetin beta into clinical practice opened new avenues to these patients. The administration of epoetins to patients with MM and anemia have been shown to be very useful. Several studies in more than 1000 patients have demonstrated a high response rate (range, 25%-85%; mean, 60%). This response is characterized by a significant increase of hemoglobin, hematocrit, and the number of red blood cells together with a reduction in the blood transfusion requirements. This is also associated with an improved quality of life. Although there is no complete agreement about the role of pretreatment serum EPO levels, many investigators believe that relatively low levels may help in predicting response, thereby limiting the number of potential candidates to receive this expensive therapy. The epoetins are safe and well tolerated with minimal toxicity; however, some concern has been recently raised regarding several dozen patients who developed pure red cell aplasia while on epoetin therapy. However, this adverse effect appears to be extremely rare. Recent data suggest that EPO has additional biologic effects, such as longer-than-expected survival in patients with MM. This observation is further supported by animal studies, demonstrating an antimyeloma effect of EPO in mice models. This effect has been shown to be immune mediated. If these exciting data are confirmed in future clinical trials, this may have significant implications on the treatment of MM.

Topics: Anemia; Animals; Cytokines; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Hemoglobins; Humans; Hypoxia; Mice; Mice, Inbred BALB C; Multiple Myeloma; Prognosis; Quality of Life; Recombinant Proteins; Time Factors

Acute exposure to moderate altitude is likely to enhance cycling performance on flat terrain because the benefit of reduced aerodynamic drag outweighs the decrease in maximum aerobic power [maximal oxygen uptake (VO2max)]. In contrast, when the course is mountainous, cycling performance will be reduced at moderate altitude. Living and training at altitude, or living in an hypoxic environment (approximately 2500 m) but training near sea level, are popular practices among elite cyclists seeking enhanced performance at sea level. In an attempt to confirm or refute the efficacy of these practices, we reviewed studies conducted on highly-trained athletes and, where possible, on elite cyclists. To ensure relevance of the information to the conditions likely to be encountered by cyclists, we concentrated our literature survey on studies that have used 2- to 4-week exposures to moderate altitude (1500 to 3000 m). With acclimatisation there is strong evidence of decreased production or increased clearance of lactate in the muscle, moderate evidence of enhanced muscle buffering capacity (beta m) and tenuous evidence of improved mechanical efficiency (ME) of cycling. Our analysis of the relevant literature indicates that, in contrast to the existing paradigm, adaptation to natural or simulated moderate altitude does not stimulate red cell production sufficiently to increase red cell volume (RCV) and haemoglobin mass (Hb(mass)). Hypoxia does increase serum erthyropoietin levels but the next step in the erythropoietic cascade is not clearly established; there is only weak evidence of an increase in young red blood cells (reticulocytes). Moreover, the collective evidence from studies of highly-trained athletes indicates that adaptation to hypoxia is unlikely to enhance sea level VO2max. Such enhancement would be expected if RCV and Hb(mass) were elevated. The accumulated results of 5 different research groups that have used controlled study designs indicate that continuous living and training at moderate altitude does not improve sea level performance of high level athletes. However, recent studies from 3 independent laboratories have consistently shown small improvements after living in hypoxia and training near sea level. While other research groups have attributed the improved performance to increased RCV and VO2max, we cite evidence that changes at the muscle level (beta m and ME) could be the fundamental mechanism. While living at altitude but training near sea le

Topics: 2,3-Diphosphoglycerate; Altitude; Bicycling; Cardiac Output; Epoetin Alfa; Erythrocyte Volume; Erythropoietin; Glycolysis; Hemoglobinometry; Humans; Hypoxia; Muscle, Skeletal; Receptors, Transferrin; Recombinant Proteins; Reticulocytes; Task Performance and Analysis

In mammals, hypoxia-triggered erythropoietin release increases red blood cell mass to meet tissue oxygen demands. Using male Wistar rats, we unmask a previously unrecognized regulatory pathway of erythropoiesis involving suppressor control by the NO metabolite and ubiquitous dietary component nitrate. We find that circulating hemoglobin levels are modulated by nitrate at concentrations achievable by dietary intervention under normoxic and hypoxic conditions; a moderate dose of nitrate administered via the drinking water (7 mg NaNO3/kg body weight/d) lowered hemoglobin concentration and hematocrit after 6 d compared with nonsupplemented/NaCl-supplemented controls. The underlying mechanism is suppression of hepatic erythropoietin expression associated with the downregulation of tissue hypoxia markers, suggesting increased pO2. At higher nitrate doses, however, a partial reversal of this effect occurred; this was accompanied by increased renal erythropoietin expression and stabilization of hypoxia-inducible factors, likely brought about by the relative anemia. Thus, hepatic and renal hypoxia-sensing pathways act in concert to modulate hemoglobin in response to nitrate, converging at an optimal minimal hemoglobin concentration appropriate to the environmental/physiologic situation. Suppression of hepatic erythropoietin expression by nitrate may thus act to decrease blood viscosity while matching oxygen supply to demand, whereas renal oxygen sensing could act as a brake, averting a potentially detrimental fall in hematocrit.

Topics: Animals; Dietary Supplements; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hemoglobins; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Immunoenzyme Techniques; Kidney; Liver; Male; Nitrates; Oxygen; Rats; Rats, Wistar; Recombinant Proteins

Exposure to intermittent hypoxia (IH) is associated with cognitive impairments and oxidative stress in brain regions involved in learning and memory. In earlier studies, erythropoietin (EPO) showed a neuroprotective effect in large doses. The aim of the present study was to explore the effect of smaller doses of EPO, such as those used in the treatment of anemia, on IH-induced cognitive deficits and hippocampal oxidative stress in young rats. The effect of concurrent EPO treatment (500 and 1,000 IU/kg/day ip) on spatial learning and memory deficits induced by long-term exposure to IH for 6 weeks was tested using the Morris water maze (MWM) test and the elevated plus maze (EPM) test. Moreover, the effect on hippocampal glutamate and oxidative stress were assessed. Exposure to IH induced a significant impairment of spatial learning and cognition of animals in both MWM and EPM performance parameters. Moreover, hippocampal glutamate and thiobarbituric acid reactive substances (TBARS) increased while antioxidant defenses (GSH and GSH-Px) decreased. EPO in the tested doses significantly reduced the IH-induced spatial learning deficits in both MWM and EPM tests and dose-dependently antagonized the effects of IH on hippocampal glutamate, TBARS, GSH levels, and GSH-Px activity. Treatment with EPO in moderate doses that used for anemia, concurrently with IH exposure can antagonize IH-induced spatial learning deficits and protect hippocampal neurons from IH-induced lipid peroxidation and oxidative stress-induced damage in young rats, possibly through multiple mechanisms involving a potential antioxidative effect.

Topics: Animals; Epoetin Alfa; Erythropoietin; Glutathione; Glutathione Peroxidase; Hippocampus; Hypoxia; Male; Maze Learning; Memory Disorders; Oxidative Stress; Rats; Recombinant Proteins

Gene therapy has been considered a promising approach for glioblastoma therapy. To avoid side effects and increase the specificity of gene expression, gene expression should be tightly regulated. In this study, glioma and hypoxia dual-specific plasmids (pEpo-NI2-SV-Luc and pEpo-NI2-SV-HSVtk) were developed by combining the erythropoietin (Epo) enhancer and nestin intron 2 (NI2). In the in vitro studies, pEpo-NI2-SV-Luc showed higher gene expression under hypoxia than normoxia in a glioblastoma-specific manner. The MTT and caspase assays demonstrated that pEpo-NI2-SV-HSVtk specifically induced caspase activity and cell death in hypoxic glioblastoma cells. For in vivo evaluation, subcutaneous and intracranial glioblastoma models were established. Dexamethasone-conjugated-polyethylenimine (PEI-Dexa) was used as a gene carrier, since PEI-Dexa efficiently delivers plasmid to glioblastoma cells and also has an antitumor effect due to the effect of dexamethasone. In the in vivo study in the subcutaneous and intracranial glioblastoma models, the tumor size was reduced more effectively in the pEpo-NI2-SV-HSVtk group than in the control and pSV-HSVtk groups. In addition, higher levels of HSVtk gene expression and TUNEL-positive cells were observed in the pEpo-NI2-SV-HSVtk group compared with the control and pSV-HSVtk groups, suggesting that pEpo-NI2-SV-HSVtk increased the therapeutic efficacy in hypoxic glioblastoma. Therefore, pEpo-NI2-SV-HSVtk/PEI-Dexa complex may be useful for glioblastoma-specific gene therapy.

Topics: Animals; Apoptosis; Blotting, Western; Cell Proliferation; Cells, Cultured; Dexamethasone; Drug Carriers; Electrophoretic Mobility Shift Assay; Enhancer Elements, Genetic; Epoetin Alfa; Erythropoietin; Flow Cytometry; Gene Transfer Techniques; Genes, Transgenic, Suicide; Glioblastoma; HEK293 Cells; Humans; Hypoxia; Immunoenzyme Techniques; Introns; Luciferases; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Nestin; Plasmids; Polyethyleneimine; Promoter Regions, Genetic; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Thymidine Kinase; Tissue Distribution; Transfection; Xenograft Model Antitumor Assays

To investigate the effect of recombine human erythropoietin (rhEPO) on apoptosis of neural cells in fetal rats after intrauterine hypoxic-ischemic injury.. Twenty SD rats on 19 days of pregnancy were divided into rhEPO (2500 U/kg, 5000 U/kg, 7500 U/kg) treated groups, ischemia-reperfusion (I/R) group and sham-operated group (4 rats in each group). Intrauterine hypoxic-ischemic injury of fetal rat was induced by bilateral occlusion of utero-ovarian artery for 20 min. rhEPO was injected into the rats in rhEPO treated group through the caudal vein 30 min before hypoxic-ischemic injury while saline was used in the other two groups. There was no hypoxic-ischemic injury in sham-operated group. The death rate of fetal rats was evaluated at 24 h after the operation, and then the brain samples of fetal rats were harvested. The expression of Caspase-3 protein was observed by immunohistochemistry. Neuroapoptosis was measured by TdT mediated dUTP-biotin nick end labeling (TUNEL) staining.. Death rates of fetal rats in rhEPO treated groups decreased compared with the I/R group (P < 0.05). Compared with the I/R group, there was less expression of copious Caspase-3 in rhEPO treated group (P < 0.01). The expression of Caspase-3 was decreased in the rhEPO treated groups with the increase of rhEPO dose (P < 0.01). Compared with the I/R group, the death rate of fetal rats in rhEPO treated groups decreased (P < 0.05), the number of apoptosis cells also decreased obviously (P < 0.01). The anti-apoptosis effect of 5000 U/kg rhEPO was similar to 7500 U/kg rhEPO, but better than 2500 U/kg rhEPO (P < 0.01).. rhEPO can inhibit the apoptosis of fetal rat brain cells after intrauterine hypoxic-ischemic injury.

Topics: Animals; Apoptosis; Brain; Caspase 3; Epoetin Alfa; Erythropoietin; Female; Fetus; Humans; Hypoxia; Neurons; Pregnancy; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Reperfusion Injury

Erythropoietin (Epo) is a key regulator of erythroid cell proliferation, differentiation and apoptosis. In the form of the recombinant protein, it is widely used to treat various types of anemias, including that associated with cancer and with the myelosuppressive effects of chemotherapy, particularly platinum-based regimens. Our previous studies confirmed the presence of Epo receptors (EpoRs) in ovarian adenocarcinoma cell lines and demonstrated that long-term Epo treatment of A2780 cells resulted in the development of a phenotype exhibiting both enhanced Epo signaling and increased paclitaxel resistance. In the present study, we carried out a series of experiments to analyze the pro-angiogenic potential of Epo-treated A2780 and SKOV-3 cells. Our studies revealed that conditioned media of Epo-treated A2780 cells had a stimulative effect on human umbilical vein endothelial cells (HUVECs). This effect was only seen when A2780 cells were incubated under hypoxic conditions. Furthermore, Epo increased the secretion of interleukin (IL)-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, GM-CSF and interferon-γ by A2780 cells that grew in hypoxic conditions. In this regard, conditioned media of hypoxic and Epo-treated A2780 cells induced a significant phosphorylation of STAT-5 in HUVECs. Our results may have important implications for ovarian cancer patients receiving Epo.

Topics: Adenocarcinoma; Blotting, Western; Cell Proliferation; Culture Media, Conditioned; Enzyme-Linked Immunosorbent Assay; Epoetin Alfa; Erythropoietin; Female; Human Umbilical Vein Endothelial Cells; Humans; Hypoxia; Neovascularization, Pathologic; Ovarian Neoplasms; Real-Time Polymerase Chain Reaction; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Cells, Cultured

Inhibition of the HIF regulating prolyl hydroxylation domain (PHDs) proteins prior to renal injury (preconditioning) has been shown to protect the kidney via activation of hypoxia-inducible transcription factors (HIF). Application of erythropoietin (EPO), one of the HIF target genes, has also been shown to be nephroprotective, and it remains unclear to what extent the effect of HIF induction is mediated by EPO. It is also unknown whether HIF activation after the onset of ischaemia (postconditioning) is still able to protect the kidney.. Using a rat model of renal ischaemia-reperfusion injury, animals were treated with the PHD inhibitor (PHD-I) 2-(1-chloro-4-hydroxyisoquinoline-3-carboxamido) acetate (ICA), vehicle (Veh) or recombinant human EPO (300 IU/kg) 6 h (ICA or Veh) or 30 min (EPO) prior to ischaemia (preconditioning) or with ICA prior to reperfusion (postconditioning). Renal function was assessed at baseline, 24 h and 72 h. After 72 h, kidneys were processed for histology and morphometric analysis. HIF immunohistochemistry and real-time polymerase chain reaction for HIF target genes, including EPO, were performed to evaluate ICA effects.. ICA treatment resulted in stabilization of HIF-1α and -2α and up-regulation of HIF target genes in a dose-dependent manner. Preconditional activation of HIF by ICA significantly improved serum creatinine levels and renal morphology in comparison to Veh (P < 0.05), while postconditional ICA treatment was ineffective. EPO therapy improved tissue morphology but had no impact on the course of serum creatinine.. These findings are in line with the concept that PHD-Is exert their protective effects through accumulation of HIF target gene products, with time requirements for increased transcription and translation of HIF-dependent genes, and suggest that their renoprotective effect is not predominately mediated by EPO.

Topics: Acute Kidney Injury; Animals; Enzyme Inhibitors; Epoetin Alfa; Erythropoietin; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Immunoenzyme Techniques; Male; Procollagen-Proline Dioxygenase; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Recombinant Proteins; Reperfusion Injury; RNA, Messenger

Autophagy is a self-degradative process that involves turnover and recycling of cytoplasmic components in healthy and diseased tissue. Autophagy has been shown to be protective at the early stages of programmed cell death but it can also promote apoptosis under certain conditions. Earlier we demonstrated that oxygen contributes to the pathogenesis of neonatal brain damage, which can be ameliorated by intervention with recombinant human erythropoietin (rhEpo). Extrinsic- and intrinsic apoptotic pathways are involved in oxygen induced neurotoxicity but the role of autophagy in this model is unclear. We analyzed the expression of autophagy activity markers in the immature rodent brain after exposure to elevated oxygen concentrations. We observed a hyperoxia-exposure dependent regulation of autophagy-related gene (Atg) proteins Atg3, 5, 12, Beclin-1, microtubule-associated protein 1 light chain 3 (LC3), LC3A-II, and LC3B-II which are all key autophagy activity proteins. Interestingly, a single injection with rhEpo at the onset of hyperoxia counteracted these oxygen-mediated effects. Our results indicate that rhEpo generates its protective effect by modifying the key autophagy activity proteins.

Topics: Animals; Apoptosis Regulatory Proteins; Autophagy; Autophagy-Related Protein 5; Autophagy-Related Proteins; Beclin-1; Brain; Epoetin Alfa; Erythropoietin; Humans; Hypoxia; Microtubule-Associated Proteins; Models, Animal; Peptide Synthases; Proteins; Rats; Rats, Wistar; Recombinant Proteins; Signal Transduction

According to recent data erythropoietin receptor (EPOR) is expressed not only by bone marrow erythroid progenitors but by endothelial- and cancer cells and it was suggested that erythropoietin (EPO) may affect their functions as well. We have analyzed the effects of recombinant human erythropoietin-alpha (rHuEPOalpha) on radiation sensitivity of EPOR+ human epidermoid carcinoma (A431) xenograft model. In vivo rHuEPOalpha treatment was started after tumor cell inoculation into SCID mice. 5 Gy irradiation was performed on day 14, the effect of which was measured on day 22. Hemoglobin level, tumor-associated microvessels and HIF-1alpha expression of the xenograft were monitored during the experiment. rHuEPOalpha administration prevented the development of tumor-induced anemia of SCID mice and reduced the level of HIF-1alpha expression of the xenograft tumor without affecting tumor growth. We have found that rHuEPOalpha treatment significantly increased the efficacy of antitumor effect of irradiation which was partly mediated by complex effects on tumor-associated microvessels. In vitro rHuEPOalpha did not affect proliferation of A431 cells but enhanced the antiproliferative and proapoptotic effects of irradiation. We concluded that rHuEPOalpha administration positively modulated the antitumoral effects of irradiation at least by two pathways, decreasing systemic hypoxia resulting in decreased tumoral HIF-1alpha expression and enhancing direct effects on tumor-associated microvessels.

Topics: Anemia, Hypochromic; Animals; Carcinoma, Squamous Cell; Cell Line, Tumor; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Mice; Mice, SCID; Microcirculation; Polymerase Chain Reaction; Radiation-Sensitizing Agents; Recombinant Proteins; Transplantation, Heterologous

Topics: Altitude; Cell Biology; Epoetin Alfa; Erythropoietin; Hypoxia; Juxtaglomerular Apparatus; Kidney; Kidney Glomerulus; Metabolism; Physiology; Rats; Research

Topics: Animals; Dogs; Epoetin Alfa; Erythropoietin; Hypoxia; Iron Isotopes; Ischemia; Kidney; Kidney Diseases; Physiology; Research

Topics: Androgens; Animals; Basal Metabolism; Drug Synergism; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hypoxia; Iron; Iron Isotopes; Mice; Nandrolone; Pharmacology; Polycythemia; Research; Starvation; Testosterone; Triiodothyronine

Topics: Adaptation, Physiological; Altitude; Anemia; Biochemical Phenomena; Biochemistry; Epoetin Alfa; Erythropoietin; Hypoxia; Iron Isotopes; Kidney; Phenylhydrazines; Rats; Research; Serum Albumin; Serum Albumin, Radio-Iodinated

Topics: Animals; Blood Urea Nitrogen; Epoetin Alfa; Erythropoietin; Hypoxia; Iron Isotopes; Kidney Diseases; Mice; Pathology; Polycythemia; Rabbits; Radiometry; Renal Artery Obstruction; Research; Reticulocytes; Urea

Topics: Anemia; Animals; Callitrichinae; Epoetin Alfa; Erythropoietin; Estrogens; Haplorhini; Hypoxia; Nephrectomy; Pharmacology; Research; Testosterone

Topics: Animals; Bone Marrow Cells; Colchicine; Epoetin Alfa; Erythrocyte Count; Erythrocytes; Erythropoiesis; Erythropoietin; Hypoxia; Iron Isotopes; Mice; Research; Reticulocytes

Topics: Anemia; Animals; Callitrichinae; Epoetin Alfa; Erythropoietin; Haplorhini; Hypoxia; Research; Saguinus

Topics: Dietary Proteins; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hypoxia; Protein Deficiency; Proteins; Rats; Research

Topics: Amniotic Fluid; Animals; Blood; Complement Fixation Tests; Epoetin Alfa; Erythroblastosis, Fetal; Erythropoietin; Female; Fetus; Hemoglobins; Humans; Hypoxia; Infant, Newborn; Maternal-Fetal Exchange; Mice; Pregnancy; Pregnancy Complications, Hematologic; Research; Reticulocytes; Rh-Hr Blood-Group System; Umbilical Cord; Urine

Topics: Anemia; Animals; Blood Volume; Bone Marrow Cells; Chromium Isotopes; Dogs; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hypoxia; Iron Isotopes; Kidney; Nephrectomy; Research; Sheep; Uremia; Ureter

Topics: Alpha-Globulins; Animals; Biochemical Phenomena; Biochemistry; Biological Products; Blood Proteins; Carbohydrates; Cattle; Chemistry Techniques, Analytical; Chymotrypsin; Epoetin Alfa; Erythropoietin; Hexosamines; Hexoses; Hypoxia; Kidney; Neuraminic Acids; Nitrogen; Perfusion; Proteins; Rabbits; Rats; Trypsin

Topics: Blood Platelets; Blood Urea Nitrogen; Bone Marrow Examination; Epoetin Alfa; Erythropoiesis; Erythropoietin; Glomerulonephritis; Hematocrit; Hemoglobinometry; Humans; Hypoxia; Iron; Iron Isotopes; Kidney; Kidneys, Artificial; Leukocyte Count; Male; Nephrectomy; Physiology; Pyelonephritis; Radioisotopes; Radionuclide Imaging; Reticulocytes; Uremia

Topics: Alpha-Globulins; Anemia; Antibodies; Biological Assay; Blood; Cerebellar Neoplasms; Electrophoresis; Epoetin Alfa; Erythropoiesis; Erythropoietin; Exudates and Transudates; Hemangiosarcoma; Humans; Hypoxia; Immune Sera; Kidney; Kidney Diseases, Cystic; Leukemia; Leukemia, Lymphoid; Neuraminidase; Trypsin

Topics: Anemia; Anemia, Aplastic; Animals; Biological Assay; Epoetin Alfa; Erythropoietin; Haplorhini; Hypoxia; Injections, Intraperitoneal; Iron Isotopes; Kidney; Mice; Nephrectomy; Pharmacology; Physiology, Comparative; Polycythemia; Rabbits; Radiometry; Research; Urine

Topics: Anabolic Agents; Androgens; Animals; Epoetin Alfa; Erythropoiesis; Erythropoietin; Hypoxia; Iron Isotopes; Mice; Nandrolone; Pharmacology; Polycythemia; Research; Steroids; Testosterone; Testosterone Congeners

Topics: Anemia; Biological Assay; Cobalt; Epoetin Alfa; Erythropoietin; Humans; Hypophysectomy; Hypoxia; Oxygen; Starvation

Topics: Abscess; Anemia; Animals; Epoetin Alfa; Erythropoietin; Hypoxia; Rats; Turpentine

Topics: Dogs; Epoetin Alfa; Erythrocytes; Erythropoietin; Hypoxia; Iron Isotopes; Kidney; Perfusion; Research

Topics: Bronchitis; Carbon Dioxide; Emphysema; Epoetin Alfa; Erythrocytes; Erythropoiesis; Erythropoietin; Humans; Hypoxia; Polycythemia; Pulmonary Emphysema; Respiratory Function Tests

Topics: Animals; Biological Assay; Epoetin Alfa; Erythropoietin; Hypoxia; Mice; Polycythemia; Research

Topics: Anemia; Animals; Biological Assay; Epoetin Alfa; Erythropoietin; Guinea Pigs; Hematocrit; Hypoxia; Iron Isotopes; Pharmacology; Phenylhydrazines; Polycythemia; Rabbits; Research

Topics: Epoetin Alfa; Erythropoietin; Humans; Hypoxia; Juxtaglomerular Apparatus; Kidney; Kidney Glomerulus

Topics: Animals; Cattle; Epoetin Alfa; Erythropoietin; Hypoxia; Kidney; Perfusion; Research; Reticulocytes

Topics: Animals; Biological Assay; Epoetin Alfa; Erythropoietin; Hypoxia; Mice; Polycythemia Vera

Topics: Animals; Epoetin Alfa; Erythrocytes; Erythropoietin; Hematopoiesis; Hypoxia; Plasma; Rabbits

Topics: Anemia; Epoetin Alfa; Erythrocytes; Erythropoietin; Hematologic Diseases; Hematopoiesis; Humans; Hypoxia

Topics: Animals; Bone Marrow; Colchicine; Epoetin Alfa; Erythroblasts; Erythrocytes; Erythropoiesis; Erythropoietin; Hypoxia; Plasma; Rats

Topics: Epoetin Alfa; Erythrocytes; Erythropoietin; Hypoxia; Liver Diseases; Plasma

Topics: Animals; Epoetin Alfa; Erythrocytes; Erythropoietin; Hypoxia; Liver Diseases; Oxygen; Plasma; Protein Binding

Topics: Animals; Epoetin Alfa; Erythrocytes; Erythropoietin; Hypoxia; Kidney; Nephrectomy; Plasma; Rats; Spleen