scholarly journals Recombinant human erythropoietin separation using a cation-exchange multimodal adsorbent

2019 ◽  
Vol 12 (1) ◽  
pp. 103-107
Author(s):  
Marta Ostrihoňová ◽  
Jana Adamíková ◽  
Tomáš Molnár ◽  
Monika Antošová ◽  
Milan Polakovič
Keyword(s):  
Cation Exchange ◽  
Chromatographic Separation ◽  
Recombinant Human Erythropoietin ◽  
Batch Adsorption ◽  
Recombinant Erythropoietin ◽  
Optimal Conditions ◽  
Effect Of Ph ◽  
Human Recombinant Erythropoietin ◽  
Human Erythropoietin ◽  
Nacl Concentration

Abstract This work deals with the capture of human recombinant erythropoietin (rhEPO) from a mixture of proteins in a concentrated postcultivation supernatant. Cation-exchange multimodal adsorbent Capto MMC ImpRes was selected as potential chromatographic separation material. Its equilibrium properties were investigated in batch adsorption experiments. The effect of pH in the range of 5.5—7.5 and NaCl concentration in the range of 0—300 mM on the adsorption of rhEPO and contaminant proteins was examined. Optimal conditions found in these equilibrium experiments were applied to rhEPO adsorption in a chromatographic column. Several experiments were carried out at different elution conditions to optimize the rhEPO yield and selectivity.

Use of recombinant human erythropoietin to avoid blood transfusion in a Jehovah's Witness requiring hemispherectomy

1993 ◽  
Vol 79 (4) ◽  
pp. 600-602 ◽  
Author(s):  
Steven J. Schiff ◽  
Steven L. Weinstein
Keyword(s):  
Blood Transfusion ◽  
Recombinant Human Erythropoietin ◽  
Recombinant Erythropoietin ◽  
Content Type ◽  
Jehovah’S Witness ◽  
Human Recombinant Erythropoietin ◽  
Jehovah's Witness ◽  
Human Erythropoietin ◽  
Witness Patient ◽  
Fine Print

✓ The use of perioperative human recombinant erythropoietin is described in a Jehovah's Witness patient. Despite significant anemia, the child's hematocrit was sufficiently increased by the use of erythropoietin so that a two-stage hemispherectomy could be performed without blood transfusion.

scholarly journals Clinical pharmacology and economics of recombinant human erythropoietin in end-stage renal disease: the case for subcutaneous administration.

1992 ◽  
Vol 2 (9) ◽  
pp. 1405-1416
Author(s):  
A Besarab ◽  
K K Flaharty ◽  
A J Erslev ◽  
J B McCrea ◽  
P H Vlasses ◽  
...  
Keyword(s):  
Clinical Pharmacology ◽  
Subcutaneous Administration ◽  
Entire Group ◽  
Pharmacokinetic Studies ◽  
Weekly Dose ◽  
Recombinant Erythropoietin ◽  
Dialysis Patients ◽  
Human Recombinant Erythropoietin ◽  
Human Erythropoietin ◽  
Stage Renal Disease

The clinical pharmacology of human recombinant erythropoietin (epoetin) was studied in order to compare the effectiveness of various routes and dosing schedules in dialysis patients. Thirty-six patients received epoetin beta three times a week i.v. for at least 12 wk. The mean dose needed to achieve target hemoglobin was 225 +/- 36 U/kg per week (median dose, 180 U/kg per week). Twenty-eight of 36 patients who were converted to a once-a-week i.v. schedule increased their requirements to 429 +/- 50 U/kg per week in order to maintain a target hematocrit of 33 to 40 vol%. Twelve of 28 patients could maintain their target hematocrit when dosed once a week s.c. at 84 +/- 10 U/kg. The other 16 patients required 137 +/- 15 U/kg per week divided into two doses. In the entire group of 28 patients, the weekly requirement for epoetin was reduced by 50% when the s.c. route was used two or three times a week. Pharmacokinetic studies performed during chronic therapy indicated rapid clearance of erythropoietin (t1/2 of 6.8 +/- 0.3 h). Single i.v. doses greater than 150 U/kg were required to increase basal erythropoietin by 30 mU/mL at 44 h postdosing. With s.c. dosing, such increments in erythropoietin levels frequently persisted beyond 60 h because of prolonged and slow absorption. Pharmacokinetic simulations in conjunction with clinical correlation of the erythropoietic response suggest that the duration that the erythropoietin levels are maintained, and not the absolute peaks, is the primary determinant of efficacy. This may result from nonlinearity in the dose response. Pharmacokinetic simulation also indicated that i.v. dosing could not maintain adequate interdialytic erythropoietin levels, whereas s.c. dosing could. Cost analysis indicated that the use of s.c. dosing two or three times a week at an average total weekly dose of 110 to 120 U/kg is effective treatment of anemia in most dialysis patients.

scholarly journals Flanker task-elicited Event Related Potential sources reflect human recombinant Erythropoietin differential effects on Parkinson’s patients

2019 ◽  
Author(s):  
Maria L Bringas Vega ◽  
Shengnan Liu ◽  
Min Zhang ◽  
Ivonne Pedroso Ibañez ◽  
Lilia M. Morales Chacon ◽  
...  
Keyword(s):  
Flanker Task ◽  
Reaction Times ◽  
Event Related Potential ◽  
Source Analysis ◽  
Random Allocation ◽  
Recombinant Erythropoietin ◽  
Human Recombinant Erythropoietin ◽  
Human Erythropoietin ◽  
Eeg Source Analysis ◽  
Eeg Recordings

AbstractWe used EEG source analysis to identify which cortical areas were involved in the automatic and controlled processes of inhibitory control on a flanker task and compared the potential efficacy of recombinant-human erythropoietin (rHuEPO) on the performance of Parkinson’ s Disease patients.The samples were 18 medicated PD patients (nine of them received rHuEPO in addition to their usual anti-PD medication through random allocation and the other nine patients were on their regular anti-PD medication only) and 9 age and education-matched healthy controls (HCs) who completed the flanker task with simultaneous EEG recordings. N1 and N2 event-related potential (ERP) components were identified and a low-resolution tomography (LORETA) inverse solution was employed to localize the neural generators.Reaction times and errors were increased for the incongruent flankers for PD patients compared to controls. EEG source analysis identified an effect of rHuEPO on the lingual gyri for the early N1 component. N2-related sources in middle cingulate and precuneus were associated with the inhibition of automatic responses evoked by incongruent stimuli differentiated PD and HCs.From our results rHuEPO, seems to mediate an effect on N1 sources in lingual gyri but not on behavioural performance. N2-related sources in middle cingulate and precuneus evoked by incongruent stimuli differentiated PD and HCs.

Influence of Recombinant Human Erythropoietin Therapy on Plasma Endothelin-1 Levels during Hemodialysis

2001 ◽  
Vol 24 (6) ◽  
pp. 367-373 ◽  
Author(s):  
I. Stefanidis ◽  
P.R. Mertens ◽  
P. Wurth ◽  
R. Bach ◽  
W. Makropoulos ◽  
...  
Keyword(s):  
Renal Disease ◽  
End Stage Renal Disease ◽  
Hemodialysis Patients ◽  
Recombinant Erythropoietin ◽  
Human Recombinant Erythropoietin ◽  
Endothelin 1 ◽  
Human Erythropoietin ◽  
Replacement Treatment ◽  
Stage Renal Disease ◽  
End Stage

The correction of anemia with human recombinant erythropoietin (rHuEPO) in end stage renal disease is associated with hypertension in about one third of hemodialysis patients. The pathogenesis of the rHuEPO-induced hypertension is still uncertain, though evidence of the involvement of endothelial cells has emerged. The aim of this study was to determine plasma endothelin-1 during hemodialysis and to compare the endothelin-1 levels in hemodialysis patients with and without rHuEPO substitution. Nineteen stable patients (13 male and 6 female, mean age 62 ± 11 years) with end stage renal disease were studied. Cuprophan dialysers (GFS 12®, Gambro, Lund, Sweden) were used for hemodialysis in all cases. rHuEPO (40U/kg s.c.) was administered to 10 patients. Blood pressure (BP; RR mmHg) and blood volume changes (ΔBV; hemoglobinometry %) were serially measured. Samples were taken before and every hour during hemodialysis. Plasma endothelin-1 was measured by ELISA (R&D Systems, Minneapolis, USA) and corrected for hemoconcentration. Endothelin-1 concentration was elevated before commencement of hemodialysis (1.16 ± 0.36 pg/ml) when compared to healthy controls (ref. 0.3 - 0.9) and increased to 1.47 ± 0.51 pg/ml by the end of the session (p<0.05). In patients under rHuEPO-substitution plasma endothelin-1 was higher when compared to patients without substitution before (1.25 ± 0.3 vs. 1.05 ± 0.3 pg/ml) and at the end of HD (1.62 ± 0.5 vs. 1.28 ± 0.3 pg/ml, p<0.05). There was no difference in BP and ΔBV between the two groups during treatment. Plasma endothelin-1 was higher in hemodialysis patients and there was a continuous rise in plasma endothelin-1 during a session. Comparison of two groups of hemodialysis patients with and without s.c. rHuEPO-replacement treatment revealed a significantly higher plasma endothelin-1 concentration in patients with s.c. rHuEPO treatment. However, the elevated endothelin-1 levels were not accompanied by arterial hypertension.

scholarly journals Survival of recombinant erythropoietin in the circulation: the role of carbohydrates

Blood ◽  
1989 ◽  
Vol 73 (1) ◽  
pp. 84-89
Author(s):  
MN Fukuda ◽  
H Sasaki ◽  
L Lopez ◽  
M Fukuda
Keyword(s):  
Recombinant Human Erythropoietin ◽  
Binding Protein ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Recombinant Erythropoietin ◽  
Lectin Affinity Chromatography ◽  
Glycoprotein Hormone ◽  
Human Erythropoietin

Recombinant human erythropoietin produced in transfected Chinese hamster ovary cells is glycosylated much the same way as the erythropoietin present in human urine. To determine the role of carbohydrates in the stability of recombinant human erythropoietin in vivo, [125I]-labeled recombinant erythropoietin was intravenously infused into rats. The erythropoietin was slowly cleared from the blood with a half-life of approximately two hours. Asialoerythropoietin, which was produced by treatment of recombinant human erythropoietin with sialidase, was found to be cleared rapidly from circulation within ten minutes. These data suggest that the galactose binding protein of hepatic cells is involved in the clearance of asialoerythropoietin. Erythropoietin also contains N-glycans with a few N-acetyllactosamine repeats, which can be enriched by tomato lectin affinity chromatography. The lectin-bound fraction was cleared to a larger extent than was the unfractionated erythropoietin, while the component that did not bind the lectin was found to be stable in the circulation. Authentic N-acetyllactosamine repeats (polylactosaminoglycans) prepared from erythrocytes were similarly rapidly cleared from the circulation to the liver, and this clearance was inhibitable with asialo-alpha 1- acid glycoprotein. These results suggest that (a) the sialic acid of the recombinant erythropoietin is necessary for this glycoprotein hormone to circulate stably and (b) glycoproteins with more than three lactosaminyl repeat units may be cleared by the galactose binding protein of hepatocytes.

Haemostatic Effects of Recombinant Human Erythropoietin in Chronic Haemodialysis Patients

1989 ◽  
Vol 61 (01) ◽  
pp. 117-121 ◽  
Author(s):  
Chris van Geet ◽  
Didier Hauglustaine ◽  
Luc Verresen ◽  
Marleen Vanrusselt ◽  
Jos Vermylen
Keyword(s):  
Platelet Count ◽  
Recombinant Human Erythropoietin ◽  
Bleeding Time ◽  
Chronic Haemodialysis ◽  
Recombinant Erythropoietin ◽  
The Third ◽  
Human Erythropoietin ◽  
Platelet Number ◽  
Almost All ◽  
And Function

SummaryRecombinant human erythropoietin was administered for up to 40 weeks to nine patients on chronic haemodialysis. From the third week of administration onwards, not only haemoglobin and haematocrit but also the platelet count rose, the latter, however, transiently. Subnormal platelet aggregation before therapy also improved transiently and in parallel with the erythropoietin dosage. The bleeding time normalized in almost all patients. There were no major side-effects. We conclude that recombinant erythropoietin improves haemostasis in chronic haemodialysis patients by increasing the haematocrit and in addition transiently enhances platelet number and function.

scholarly journals The in vivo metabolism of recombinant human erythropoietin in the rat

Blood ◽  
1989 ◽  
Vol 73 (1) ◽  
pp. 90-99 ◽  
Author(s):  
JL Spivak ◽  
BB Hogans
Keyword(s):  
Recombinant Human Erythropoietin ◽  
Plasma Clearance ◽  
Dextran Sulfate ◽  
Volume Of Distribution ◽  
Human Albumin ◽  
Recombinant Erythropoietin ◽  
Elimination Phase ◽  
Human Erythropoietin ◽  
Distribution Phase

Abstract We compared the in vivo plasma clearance and organ accumulation in anesthetized rats of 125I-labeled, recombinant human erythropoietin and 125I-labeled, desialylated recombinant erythropoietin. The immediate volume of distribution of 125I-labeled, recombinant erythropoietin approximated that of the plasma volume. Its plasma clearance was multiexponential, with an initial rapid distribution phase (t1/2 = 53 minutes) and a slower elimination phase (t1/2 = 180 minutes). Organ accumulation of labeled recombinant erythropoietin, as compared with 125I-labeled human albumin, was negligible until 30 minutes after injection when small amounts appeared in the kidneys and bone marrow. Only 24% of the 125I-labeled, desialylated recombinant erythropoietin was recovered immediately after injection, and 96% of the hormone was cleared from the plasma with a t1/2 of 2.0 minutes. The bulk of the desialylated hormone accumulated in the liver where it was rapidly catabolized and its breakdown products released back into the plasma. Significantly, in contrast to unmodified erythropoietin, there was also early accumulation of desialylated hormone in the kidneys, marrow, and spleen. Desialylated orosomucoid but not orosomucoid, yeast mannan, or dextran sulfate 500 inhibited the rapid plasma clearance and hepatic accumulation of desialylated erythropoietin. Oxidation of the desialylated hormone restored its plasma recovery and clearance to normal but rendered it biologically inactive, and accumulation in organs other than the kidney was negligible.

Novel tissue remodelling roles for human recombinant erythropoietin

2005 ◽  
Vol 33 (5) ◽  
pp. 1129-1130 ◽  
Author(s):  
P.J. Coussons ◽  
S. Baig ◽  
C. Fanutti ◽  
R. Grant
Keyword(s):  
Multiple Roles ◽  
Chronic Congestive Heart Failure ◽  
Recombinant Erythropoietin ◽  
Tissue Remodelling ◽  
Human Recombinant Erythropoietin ◽  
Cellular Processes ◽  
Human Erythropoietin ◽  
Chronic Anaemia ◽  
Broad Array ◽  
Exciting Possibility

rHuEPO (recombinant human erythropoietin) is a haemopoietic growth factor and a primary regulator of erythropoiesis that is used for the treatment of chronic anaemia associated with RA (rheumatoid arthritis). Erythropoietin also appears to modulate a broad array of cellular processes, including progenitor stem-cell development, cellular integrity, angiogenesis and oxidative damage. These diverse activities suggest the exciting possibility of multiple roles for rHuEPO therapy in a variety of disorders other than RA, including cerebral ischaemia, myocardial infarction, chronic congestive heart failure and cancer. Thus it appears that rHuEPO may be a pleiotropic agent, capable of influencing tissue remodelling independently of its established erythropoietic role. Whereas these effects may be largely beneficial, dose-related side effects could have implications for the safe therapeutic use of rHuEPO and its illegal use as a performance-enhancing agent in endurance sports.

scholarly journals The in vivo metabolism of recombinant human erythropoietin in the rat

Blood ◽  
1989 ◽  
Vol 73 (1) ◽  
pp. 90-99
Author(s):  
JL Spivak ◽  
BB Hogans
Keyword(s):  
Recombinant Human Erythropoietin ◽  
Plasma Clearance ◽  
Dextran Sulfate ◽  
Volume Of Distribution ◽  
Human Albumin ◽  
Recombinant Erythropoietin ◽  
Elimination Phase ◽  
Human Erythropoietin ◽  
Distribution Phase

We compared the in vivo plasma clearance and organ accumulation in anesthetized rats of 125I-labeled, recombinant human erythropoietin and 125I-labeled, desialylated recombinant erythropoietin. The immediate volume of distribution of 125I-labeled, recombinant erythropoietin approximated that of the plasma volume. Its plasma clearance was multiexponential, with an initial rapid distribution phase (t1/2 = 53 minutes) and a slower elimination phase (t1/2 = 180 minutes). Organ accumulation of labeled recombinant erythropoietin, as compared with 125I-labeled human albumin, was negligible until 30 minutes after injection when small amounts appeared in the kidneys and bone marrow. Only 24% of the 125I-labeled, desialylated recombinant erythropoietin was recovered immediately after injection, and 96% of the hormone was cleared from the plasma with a t1/2 of 2.0 minutes. The bulk of the desialylated hormone accumulated in the liver where it was rapidly catabolized and its breakdown products released back into the plasma. Significantly, in contrast to unmodified erythropoietin, there was also early accumulation of desialylated hormone in the kidneys, marrow, and spleen. Desialylated orosomucoid but not orosomucoid, yeast mannan, or dextran sulfate 500 inhibited the rapid plasma clearance and hepatic accumulation of desialylated erythropoietin. Oxidation of the desialylated hormone restored its plasma recovery and clearance to normal but rendered it biologically inactive, and accumulation in organs other than the kidney was negligible.

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