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Céline Joré, Benoît Loup, Patrice Garcia, Anne-Christelle Paris, Marie-Agnès Popot, Michel Audran, Yves Bonnaire, Emmanuelle Varlet-Marie, Ludovic Bailly-Chouriberry
Erythropoiesis Stimulating Agents (ESAs) were developed for therapeutic purposes to stimulate red blood cell (RBC) production. Consequently, tissue oxygenation is enhanced as athlete's endurance and ESAs misuse now benefits doping. Our hypothesis is that most of ESAs should have similar mechanisms and thus have the same effects on metabolism. Studying the metabolome variations could allow suspecting the use of any ESAs with a single method by targeting their effects. In this objective, a metabolomic study was carried out on 3 thoroughbred horses with a single administration of 4...
October 27, 2017: Journal of Chromatography. A
Céline Joré, Jean-Frédéric Brun, Emmanuelle Varlet-Marie
Erythropoietin (EPO) is a major regulator of blood viscosity. Its long lasting action analogue methoxy polyethylene glycol-epoetin-β (MIRCERA®) seems to be also employed in modern doping. We took the opportunity of a study aiming at developing a detection of recent MIRCERATM injection in the context of doping detection to assess the effects of this EPO analogue on red blood cells (RBC) aggregation. A single dose 200 μg of MIRCERA® was injected to 10 male volunteers and blood samplings were drawn over 24 days...
2016: Clinical Hemorheology and Microcirculation
Mark Timms, Rohan Steel, John Vine
The recombinant human erythropoietins epoetin alfa (Eprex®), darbepoetin (Aranesp®) and methoxy polyethylene glycol-epoetin beta (Mircera®) were administered to greyhounds for 7, 10 and 14 days respectively. Blood and urine samples were collected and analysed for erythropoietin by ELISA, LC-MS/MS and western blotting. Limits of confirmation in plasma for western blotting and LC-MS/MS methods ranged from a low of 2.5mIU/mL, and closely matched the sensitivity of ELISA screening.
February 2016: Drug Testing and Analysis
Cécile Vigneau, Sylvie Le Stum, Corinne Isnard-Bagnis, Gabriel Choukroun, Yannick Lemeur, Nassim Kamar, Emmanuel Oger
INTRODUCTION: Erythropoiesis Stimulating Agents (ESA) are largely prescribed before dialysis stage to chronic kidney disease patients. In accordance to current international guidelines, lots have been made by pharmacological companies in order to improve self management of ESAs: subcutaneaous administration, pencil devices, mutidose cartridges, low injection volume, very fine needles, once a month injections but none is currently known on the percentage of patients who actually do self administration of ESAs...
December 2014: Néphrologie & Thérapeutique
Piotr Bartnicki, Paweł Fijałkowski, Małgorzata Majczyk, Jan Błaszczyk, Maciej Banach, Jacek Rysz
BACKGROUND: There is data in the literature indicating increased oxidative stress in chronic kidney disease (CKD). Erythropoiesisstimulating agents (ESAs), which are commonly used to treat anemia in patients with CKD, seem to have an antioxidant action, which could be a part of nephroprotection. The aim of the current study was to investigate the effect of a long half-life ESA, methoxy polyethylene glycol-epoetin beta (Mircera), on some markers of oxidative stress in predialysis patients with CKD...
2013: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Peter Choi, Mourad Farouk, Nick Manamley, Janet Addison
INTRODUCTION: There is limited information published on switching erythropoiesis-stimulating agent (ESA) treatment for anemia associated with chronic kidney disease (CKD) from darbepoetin alfa (DA) to methoxy polyethylene glycol-epoetin beta (PEG-Epo) outside the protocol of interventional clinical studies. AFFIRM (Aranesp Efficiency Relative to Mircera) was a retrospective, multi-site, observational study designed to estimate the population mean maintenance dose conversion ratio [DCR; dose ratio achieving comparable hemoglobin level (Hb) between two evaluation periods] in European hemodialysis patients whose treatment was switched from DA to PEG-Epo...
November 2013: Advances in Therapy
José M Mora-Gutiérrez, Asunción Ferrer-Nadal, Nuria García-Fernández
INTRODUCTION AND OBJECTIVES: Treatment of anaemia in haemodialysis (HD) with iron and erythropoiesis-stimulating agent (ESA) does not lead to adequate anaemia control and has been associated with inflammation. The anti-inflammatory effect of pentoxifylline (PTX) may be beneficial in these cases. Our aim was to study the potential effect of PTX on anaemia in haemodialysis patients. PATIENTS AND METHOD: Retrospective observational case-control study on 18 patients (treated with PTX) and 18 controls (without PTX matched by age and sex) on HD (Clínica Universidad de Navarra)...
2013: Nefrología: Publicación Oficial de la Sociedad Española Nefrologia
Philippe Desharnais, Jean-François Naud, Christiane Ayotte
Recombinant erythropoietin (rhEPO) has been misused for over two decades by athletes, mainly but not only in endurance sports. A direct rhEPO detection method in urine by isoelectric focusing (IEF) was introduced in 2000, but the emergence of third-generation erythropoiesis-stimulating agents and so-called biosimilar rhEPOs, together with the sensitivity of human endogenous EPO (huEPO) pattern to enzymatic activities and its modification following short strenuous exercise, prompted the development of a complementary test based on SDS-PAGE analysis...
November 2013: Drug Testing and Analysis
Ivan Bubić, Ingrid Prkacin, Sanjin Racki
AIM: To evaluate efficacy and safety of CERA (continuous erythropoietin receptor activator) administration for correcting anemia in the patients with chronic kidney disease (CKD), not on dialysis. METHODS: We performed observational study on 27 CKD patients in stage 4 or 5 with renal anemia requiring use of erythropoiesis-stimulating agents (ESA). All patients received CERA (Mircera; Roche, Basel, Switzerland) subcutaneously in dose of 0.6 microg per kg every two weeks during the correction phase of anemia treatment or once monthly during the maintenance treatment...
October 2012: Acta Medica Croatica: C̆asopis Hravatske Akademije Medicinskih Znanosti
Luc Frimat, Christophe Mariat, Paul Landais, Sébastien Koné, Bénédicte Commenges, Gabriel Choukroun
OBJECTIVE: The aim of this study was to describe the management of anaemia with a continuous erythropoietin receptor activator (C.E.R.A., methoxy polyethylene glycol epoetin-β), in patients with chronic kidney disease (CKD) not on dialysis, naïve or non-naïve to treatment with erythropoiesis-stimulating agents (ESAs) at inclusion. DESIGN: National, multicentre, longitudinal, observational prospective study. SETTING: 133 nephrologists practicing in France selected patients during their routine follow-up visits...
2013: BMJ Open
Bader Al-Khalaf, Nour Al-Khalaf, Seham Mustafa
Anemia is a common feature in chronic kidney disease patients due to deficiency of erythropoietin (EPO). Diseased kidneys are unable to produce EPO, which enhances red blood cell production from the bone marrow. Recombinant human EPO in hemodialysis patients was introduced with perfect outcomes as a hormonal substitutive treatment. Some ethnic minority groups have high prevalence of anemia associated with chronic kidney diseases. The aim of this study is to evaluate the differences between African Caribbeans and Caucasians' EPO therapy response with regard to hemoglobin (Hb), some factors affecting it and some comorbid conditions...
October 2013: Hemodialysis International
Christian Reichel
PEGylation of recombinant proteins and synthetic peptides aims to generate biopharmaceuticals with altered physical properties. The modification may lead to a prolonged serum half-life caused by a decreased receptor-mediated endocytosis and/or a delay in renal clearance caused by the increased hydrodynamic volume of the pharmaceutical. MIRCERA, a PEGylated recombinant erythropoietin (rhEpo) frequently used in the treatment of anemia due to chronic kidney disease, has been also abused by athletes as a performance-enhancing drug...
2012: Methods in Molecular Biology
Thomas Weinreich, Frank Leistikow, Hagen-Georg Hartmann, Günter Vollgraf, Frank Dellanna
Once-monthly administration of CERA, a continuous erythropoietin receptor activator, has shown equivalent efficacy to shorter-acting erythropoiesis-stimulating agents (ESAs) that require more frequent dosing, but data on routine use of once-monthly CERA in hemodialysis patients are lacking. Study on Efficacy, Safety and Applicability of Mircera (SESAM) was a prospective, multicenter, noninterventional trial with a duration of up to 9 months (month 0-5 "titration phase"; month 6-8 "evaluation phase") to test the stability of Hb control in hemodialysis patients under routine conditions...
January 2012: Hemodialysis International
Nicholas M Selby, Sally A Fonseca, Richard J Fluck, Maarten W Taal
BACKGROUND AND OBJECTIVES: The extent to which hemoglobin (Hb) cycling occurs in peritoneal dialysis (PD) patients is unclear. It is also uncertain whether different types of erythropoiesis-stimulating agents (ESAs) affect such cycling. We performed a retrospective cohort study of our PD population before and after the entire program was switched from epoetin beta (NeoRecormon: Hoffman-LaRoche, Basel, Switzerland) to continuous erythropoietin receptor activator [CERA (Mircera: Hoffman-LaRoche)]...
March 2012: Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis
Maria Lönnberg, Maria Andrén, Gunnar Birgegård, Malin Drevin, Mats Garle, Jan Carlsson
A rapid and easy-to-use test kit, EPO WGA MAIIA, which can be used for distinguishing various endogenous human erythropoietins (hEPOs) and several recombinant hEPO and EPO analogues, has been evaluated. The test is based on chromatographic separation of the glycosylated isoforms of EPO using wheat germ agglutinin (WGA) and a sensitive immunoassay using anti-EPO carbon black nanostrings and image scanning for quantification. All of the reactions take place along the porous layer of a lateral flow microcolumn containing WGA and anti-EPO zones...
January 15, 2012: Analytical Biochemistry
Christian Reichel
The constant development of new erythropoiesis-stimulating agents (ESAs), since the first introduction of recombinant erythropoietin (rhEpo) for clinical use, has also necessitated constant development of methods for detecting the abuse of these substances. Doping with ESAs is prohibited according to the World Anti-Doping Code and its prohibited list of substances and methods. Since the first publication of a direct and urine-based detection method in 2000, which uses changes in the Epo isoform profile as detected by isoelectric focusing in polyacrylamide slab gels (IEF-PAGE), the method has been constantly adapted to the appearance of new ESAs (e...
August 2011: Analytical and Bioanalytical Chemistry
Yvette Dehnes, Peter Hemmersbach
Erythropoietin (EPO) has been misused in sports for many years due to its performance-enhancing effect. In the last decade, detection of abuse has been possible with isoelectric focusing (IEF) based on the different isoform profiles of endogenous and recombinant EPO. The release of new EPOs on the market, such as the recombinant erythropoietin epoetin delta (Dynepo™) and the chemically modified EPO, CERA (Mircera™) potentially represents analytical challenges to the fight against doping. This study set out to investigate the possibility of and the time window for detecting the administration of a single dose of Dynepo™ and CERA...
May 2011: Drug Testing and Analysis
Y Chang, G M Maylin, G Matsumoto, S M Neades, D H Catlin
Methods have been developed to screen for and confirm darbepoetin alfa, recombinant human EPO, and methoxy polyethylene glycol-epoetin β (PEG-epoetin β) in horse plasma. All three methods screen samples with an enzyme-linked immunosorbent assay (ELISA) and confirm by liquid chromatography-tandem mass spectrometry (LC-MS/MS). This report focuses on PEG-epoetin β. The ELISA assay was able to detect PEG-epoetin β at 0.02 ng/mL in 50 µL of horse plasma. Many samples had high background levels of immunoreactivity; however, introducing polyethylene glycol 6000 (PEG 6000) into the samples before the ELISA assay removed the high background and increased the apparent concentrations of PEG-epoetin β...
January 2011: Drug Testing and Analysis
A Sánchez-Fructuoso, L Guirado, J C Ruiz, V Torregrosa, E González, M L Suárez, R Gallego
BACKGROUND: Kidney transplant, the gold standard treatment for chronic kidney disease (CKD), is increasingly complicated by anemia. Once-monthly dosing of methoxy polyethylene glycol-epoetin beta provides stable, sustained hemoglobin levels in CKD patients. The present study evaluated anemia control in recipients treated with methoxy polyethylene glycol-epoetin beta to correct or as conversion treatment from other erythropoiesis-stimulating agents (ESAs). PATIENTS AND METHODS: This observational, retrospective study included kidney transplant patients treated with methoxy polyethylene glycol-epoetin beta according to investigators' clinical practice...
October 2010: Transplantation Proceedings
Maria Lönnberg, Yvette Dehnes, Malin Drevin, Mats Garle, Severine Lamon, Nicolas Leuenberger, Trikien Quach, Jan Carlsson
Identification of post-translational modifications of proteins in biological samples often requires access to preanalytical purification and concentration methods. In the purification step high or low molecular weight substances can be removed by size exclusion filters, and high abundant proteins can be removed, or low abundant proteins can be enriched, by specific capturing tools. In this paper is described the experience and results obtained with a recently emerged and easy-to-use affinity purification kit for enrichment of the low amounts of EPO found in urine and plasma specimens...
November 5, 2010: Journal of Chromatography. A
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