Novel tissue remodelling roles for human recombinant erythropoietin

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.

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

Journal of the American Society of Nephrology ◽

10.1681/asn.v291405 ◽

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.

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

10.1101/864397 ◽

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.

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

The International Journal of Artificial Organs ◽

10.1177/039139880102400608 ◽

2001 ◽

Vol 24 (6) ◽

pp. 367-373 ◽

Cited By ~ 11

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.

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Recombinant human erythropoietin separation using a cation-exchange multimodal adsorbent

Acta Chimica Slovaca ◽

10.2478/acs-2019-0015 ◽

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.

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

Journal of Neurosurgery ◽

10.3171/jns.1993.79.4.0600 ◽

1993 ◽

Vol 79 (4) ◽

pp. 600-602 ◽

Cited By ~ 13

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.

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Flanker Task-Elicited Event-Related Potential Sources Reflect Human Recombinant Erythropoietin Differential Effects on Parkinson’s Patients

Parkinson s Disease ◽

10.1155/2020/8625794 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

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

We 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 were evoked by incongruent stimuli differentiated PD and HCs.

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