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Britt Christensen, Birgitte Nellemann, Jens Otto L Jørgensen, Steen B Pedersen, Niels Jessen
BACKGROUND: Erythropoietin (Epo) exerts direct effects on white adipose tissue (WAT) in mice in addition to its erythropoietic effects, and in humans Epo increases resting energy expenditure and affect serum lipid levels, but direct effects of Epo in human WAT have not been documented. We therefore investigated the effects of acute and prolonged Epo exposure on human WAT in vivo. METHOD: Data were obtained from two clinical trials: 1) acute Epo exposure (rHuEpo, 400 IU/kg) followed by WAT biopsies after 1 h and 2) 10 weeks treatment with the erythropoiesis-stimulating agent (ESA) Darbepoietin-alpha...
September 17, 2016: Lipids in Health and Disease
Krzysztof Chojnowski, Agnieszka Janus, Katarzyna Bliźniewska, Marta Robak, Jacek Treliński
BACKGROUND: The treatment of patients with acute leukemia, who due to their religious beliefs refuse to accept blood transfusion, is a great challenge for hematologists. CASE REPORT: We present a case of acute pre-T-lymphoblastic leukemia in a Jehovah's Witness who did not accept blood transfusion during chemotherapy. Standard induction and consolidation chemotherapy was used (according to the PALG ALL-6 regiment). RESULTS: During consolidation cycles, darbepoietin alfa, intravenous iron, and total parenteral nutrition was administered...
October 2016: Transfusion
Rakesh Verma, Jennifer M Green, Peter J Schatz, Don M Wojchowski
Erythropoiesis-stimulating agents (ESAs) that exert long-acting antianemia effects have been developed recently, but their mechanisms are poorly understood. Analyses reveal unique erythropoietin receptor (EPOR)-binding properties for one such ESA, the synthetic EPOR agonist peginesatide. Compared with recombinant human EPO and darbepoietin, peginesatide exhibited a slow on rate, but sustained EPOR residency and resistant displacement. In EPO-dependent human erythroid progenitor UT7epo cells, culture in peginesatide unexpectedly upmodulated endogenous cell surface EPOR levels with parallel increases in full-length EPOR-68K levels...
August 2016: Experimental Hematology
M R Jain, A A Joharapurkar, V Pandya, V Patel, J Joshi, S Kshirsagar, K Patel, P R Patel, R C Desai
Prolyl hydroxylase (PHD) inhibitors stabilize hypoxia inducible factor (HIF), and exert antianemic effect by potentiating erythropoietin (EPO) expression and down-regulation of hepcidin. ZYAN1 is a novel PHD inhibitor under clinical development for the treatment of anemia. The pharmacodynamic effects of acute and chronic dosing of ZYAN1 were assessed in normal and 5/6 nephrectomized Wistar rats. The effect of ZYAN1 was also investigated in cisplatin-induced anemia using C57 mice. Acute treatment with ZYAN1 increased circulating EPO levels (10...
February 2016: Drug Research
Britt Christensen, Maja Ludvigsen, Birgitte Nellemann, John J Kopchick, Bent Honoré, Jens Otto L Jørgensen
INTRODUCTION: Despite implementation of the biological passport to detect erythropoietin abuse, a need for additional biomarkers remains. We used a proteomic approach to identify novel serum biomarkers of prolonged erythropoiesis-stimulating agent (ESA) exposure (Darbepoietin-α) and/or aerobic training. TRIAL DESIGN: Thirty-six healthy young males were randomly assigned to the following groups: Sedentary-placebo (n = 9), Sedentary-ESA (n = 9), Training-placebo (n = 10), or Training-ESA (n = 8)...
2015: PloS One
Brian A Baldo
Cytokines, currently known to be more than 130 in number, are small MW (<30 kDa) key signaling proteins that modulate cellular activities in immunity, infection, inflammation and malignancy. Key to understanding their function is recognition of their pleiotropism and often overlapping and functional redundancies. Classified here into 9 main families, most of the 20 approved cytokine preparations (18 different cytokines; 3 pegylated), all in recombinant human (rh) form, are grouped in the hematopoietic growth factor, interferon, platelet-derived growth factor (PDGF) and transforming growth factor β (TGFβ) families...
November 2014: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
Britt Christensen, Birgitte Nellemann, Kasper Thorsen, Morten Muhlig Nielsen, Steen B Pedersen, Marie Juul Ornstrup, Jens Otto L JØrgensen, Niels Jessen
INTRODUCTION: We tested for the presence of erythropoietin receptor (Epo-R) in human skeletal muscle and alterations in gene expression after prolonged use of an erythropoiesis-stimulating agent (ESA). METHODS: Nine healthy men were treated with ESA for 10 weeks (darbepoietin alfa). Muscle biopsies were collected before and after treatment. Alterations in gene expression were evaluated by gene array. Western blot and PCR analysis were used to test for Epo-R presence in human skeletal muscle...
April 2015: Muscle & Nerve
Jametta S Magwood, Akida Lebby, Brian Chen, Sam Kessler, LeAnn Norris, Charles L Bennett
INTRODUCTION: Erythropoiesis-stimulating agents (ESAs) prevent transfusions among anemic patients with chronic kidney disease (CKD). Clinical trials, meta-analyses, and guidelines identify arterial and venous thromboembolism as well as myocardial event risks with the traditional ESAs, erythropoietin (EPO), and darbepoietin. Side effects of anemia treatment, considering frequency and dosage of treatment as well as targeted hemoglobin levels when utilizing ESAs, greatly impact overall well-being and the quality of life...
December 2013: Expert Opinion on Emerging Drugs
Sita R Dewamitta, Megan R Russell, Harshal Nandurkar, Carl R Walkley
Erythropoiesis stimulating agents are widely used for the treatment of anemia. Recently, we reported erythroid expansion with impaired B lymphopoiesis and loss of trabecular bone in C57BL/6 mice following ten days of treatment with low-dose short acting recombinant human erythropoietin. We have assessed erythropoietin against longer-acting darbepoietin-alfa at a comparable erythroid stimulatory dosage regime. Darbepoietin-alfa and erythropoietin induced similar in vivo erythropoietic expansion. Both agents induced an expansion of the colony-forming unit-erythroid populations...
May 2013: Haematologica
Anna Jander, Ryszard Wierciński, Irena Bałasz-Chmielewska, Monika Miklaszewska, Katarzyna Zachwieja, Halina Borzecka, Jacek Zachwieja, Irena Olszak-Szot, Dariusz Kubicki, Helena Ziółkowska, Jacek Rubik, Maria Szczepańska, Dariusz Runowski, Wojciech Fendler, Marcin Tkaczyk
OBJECTIVE: Erythropoiesis-stimulating agents (ESAs) are applied as a standard therapy in children with anaemia in chronic kidney disease. The aim of this study was to describe the efficacy and details of ESA treatment in a population of dialysed children in Poland. MATERIAL AND METHODS: The study had a prospective observational design and was performed in 12 dialysis centres. The study group comprised 117 dialysed children with a mean age at enrolment of 165.33 (97...
October 2012: Scandinavian Journal of Urology and Nephrology
Claudia Kessler, Alexandra Greindl, Bettina Breuer, Udo Haberl, Andreas Rybka, Marco Emgenbroich, Hans-Georg Frank, Andy J G Pötgens
EPO mimetic peptides (EMPs) have a completely different structure than erythropoietin (EPO) or new generation recombinant erythropoiesis stimulating agents (ESAs) like Darbepoietin alfa (Aranesp) and continuous erythropoiesis stimulating agent (CERA). This study intended to compare the effects of a novel compound called AGEM400(HES), consisting of a dimeric EMP conjugated to hydroxyethyl starch (HES), to those of recombinant EPO. AGEM400(HES) efficiently stimulated erythropoiesis in vitro and efficiently stimulated survival of EPO-dependent cell line UT7/EPO...
February 2012: Cytokine
Leela Cherian, J Clay Goodman, Claudia Robertson
Darbepoetin alfa (darbEpo) is an erythropoietic glycoprotein that activates the erythropoietin receptor. The aim of our study was to determine whether darbEpo is neuroprotective in a cortical impact injury (CII) model and to determine the characteristics of dose response and time window. To better understand the vascular mechanism of darbEpo neuroprotection, the reactivity of cerebral blood flow (CBF) to l-arginine administration was also studied. Rats were given saline or darbEpo from 2.5 to 50 μg/kg at 5 min after CII or a dose of 25 μg/kg darbEpo at times ranging from 5 min to 24 h after CII...
May 2011: Journal of Pharmacology and Experimental Therapeutics
Ashok K Singh, Shveta Gupta
Darbepoietin (DAR) and recombinant human erythropoietin (rhEPO) stimulate erythropoiesis, leading to an increase in red blood cells. Along with their legitimate clinical use, rhEPO and DAR are also misused in racing horses for performance enhancement. To control the illegal use of DAR and rhEPO, it is important to develop analytical methods for the detection and confirmation of these proteins in plasma. Analysis of rhEPO and DAR in plasma is challenging due to the presence of a number of high abundance proteins including albumin that interferes with their extraction...
July 2007: Proteomics. Clinical Applications
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
Patrícia João Matias, Cristina Jorge, Carina Ferreira, Marília Borges, Inês Aires, Tiago Amaral, Célia Gil, José Cortez, Aníbal Ferreira
BACKGROUND AND OBJECTIVES: Vitamin D deficiency is highly prevalent in chronic kidney disease. The aim of this study was to evaluate the effects of oral cholecalciferol supplementation on mineral metabolism, inflammation, and cardiac dimension parameters in long-term hemodialysis (HD) patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This 1-year prospective study included 158 HD patients. Serum levels of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2)D], intact parathyroid hormone, and plasma brain natriuretic peptide as well as circulating bone metabolism and inflammation parameters were measured before and after supplementation...
May 2010: Clinical Journal of the American Society of Nephrology: CJASN
William Cáceres, Karen Santiago, Liza Paulo, Jaime Román
Patients with multiple myeloma (MM) have a high rate of infectious complications and symptomatic anemia. Emerging antineoplastic therapies are resulting in a better response, but still quality of life and potentially survival can be significantly affected by these complications. Multiple cytokines and an impaired immunologic system are involved in the development of these complications. Emerging therapies and guidelines will be reviewed taking in consideration the benefits versus risks of those strategies. The beneficial effect of recombinant human erythropoietin (EPO) and darbepoietin alpha in MM patients have been confirmed in several trials...
April 2009: Boletín de la Asociación Médica de Puerto Rico
Dawn L Hershman, Donna L Buono, Jennifer Malin, Russell McBride, Wei Yann Tsai, Alfred I Neugut
BACKGROUND: Erythropoiesis-stimulating agents (erythropoietin and darbepoietin) have been approved to reduce the number of blood transfusions required during chemotherapy; however, concerns about the risks of venous thromboembolism and mortality exist. METHODS: We identified patients who were aged 65 years or older in the Surveillance, Epidemiology, and End Results-Medicare database; who were diagnosed with colon, non-small cell lung, or breast cancer or with diffuse large B-cell lymphoma from January 1, 1991, through December 31, 2002; and who received chemotherapy...
December 2, 2009: Journal of the National Cancer Institute
P M Ter Wee, Y de Koter, O van der Veer, M H van Vliet
Although immediate pain sensation at the injection site is reported by patients, only limited data on comparison of pain at the injection site between erythropoiesis stimulating agents are available. Therefore, we compared the effect of subcutaneous epoietin-beta on immediate pain sensation to that of subcutaneous darbepoietin-alpha in a double blind, randomized controlled study. Adult patients, aged 18 - 75 years, treated with peritoneal dialysis or with stage 4 chronic kidney disease who in our unit are treated with subcutaneous darbepoietin-alpha for renal anemia for at least 3 months, were eligible for the study...
September 2009: Clinical Nephrology
Geo Serban, Vaughn Whittaker, Jianshe Fan, Zhouru Liu, Kiran Manga, Muzammil Khan, Katerina Kontogianni, Anand Padmanabhan, David Cohen, Nicole Suciu-Foca, Lloyd Ratner, Adriana I Colovai
Monitoring of immune status in transplant recipients is essential for predicting the risk of rejection or infection. In this study, we assessed the significance of immune cell function in 76 renal allograft recipients after Thymoglobulin induction and initiation of maintenance immunosuppression. Using the Immuknow (Cylex Inc) assay, the amount of adenosine triphosphate (ATP) produced by CD4+ cells in response to phytohemagglutinin (PHA) was measured in patients whole blood. In parallel, the frequency and phenotype of CD4+ T cells were determined by flow cytometry...
November 2009: Human Immunology
Katherine A Barraclough, Euan Noble, Diana Leary, Fiona Brown, Carmel M Hawley, Scott B Campbell, Nicole M Isbel, David W Mudge, Carolyn L van Eps, Joanna M Sturtevant, David W Johnson
BACKGROUND: The main hypothesis of this study is that oral heme iron polypeptide (HIP; Proferrin ES) administration will more effectively augment iron stores in erythropoietic stimulatory agent (ESA)-treated peritoneal dialysis (PD) patients than conventional oral iron supplementation (Ferrogradumet). METHODS: Inclusion criteria are peritoneal dialysis patients treated with darbepoietin alpha (DPO; Aranesp(R), Amgen) for >or= 1 month. Patients will be randomized 1:1 to receive either slow-release ferrous sulphate (1 tablet twice daily; control) or HIP (1 tablet twice daily) for a period of 6 months...
2009: BMC Nephrology
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