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Jaime S Rosa, Van B Vuong, Orly Haskin, Anne Y Liu
Background: Recombinant human erythropoietin, such as epoetin alfa and darbepoetin alfa, is an important therapy for anemia due to chronic renal failure. Allergy to recombinant human erythropoietin and the need for desensitization are rare. Case presentation: We report here a novel epoetin alfa outpatient desensitization protocol in a girl who developed delayed cutaneous hypersensitivity to subcutaneous epoetin alfa and intravenous darbepoetin alfa. An initial attempt at traditional epoetin alfa desensitization failed, so we created a slower 17-day outpatient desensitization that succeeded and allowed treatment continuation...
2018: Allergy, Asthma, and Clinical Immunology
Wendy L St Peter, Haifeng Guo, Shaum Kabadi, David T Gilbertson, Yi Peng, Trudy Pendergraft, Suying Li
BACKGROUND: Anemia is common in non-dialysis-dependent chronic kidney disease (NDD-CKD) patients, but detailed information on prevalence and treatment is lacking. METHODS: We evaluated anemia prevalence and treatment using two datasets: the Medicare 20% random sample (ages 66-85 years), and the Truven Health MarketScan database (ages 18-63 years). We selected stage 3-5 NDD-CKD patients with and without anemia from both databases during 2011-2013. We evaluated anemia prevalence and treatment (erythropoietin stimulating agents [ESAs], intravenous [IV] iron, red blood cell [RBC] transfusions) following anemia diagnosis during a 1-year baseline period, and healthcare utilization during a 1-year follow-up period...
March 15, 2018: BMC Nephrology
Asim Badar, Zarina Arif, Khursheed Alam
Carbamylation (or carbamoylation) is a non-enzymatic modification of biomolecules mediated by cyanate, a dissociation product of urea. Proteins are more sensitive to carbamylation. Two major sites of carbamylation reaction are: Nα -amino moiety of a protein N-terminus and the Nɛ -amino moiety of proteins' lysine residues. In kidney diseases, urea accumulates and the burden of carbamylation increases. This may lead to alteration in the structure and function of many important proteins relevant in maintenance of homeostasis...
March 15, 2018: IUBMB Life
Nariaki Asada
Kidneys are physiologically hypoxic due to huge oxygen consumption for tubular reabsorption. The physiological hypoxia makes the kidney an appropriate organ for sensitively detecting oxygen levels and producing erythropoietin (EPO). In preterm neonates, immature kidneys cannot produce sufficient EPO, which results in anemia of prematurity (AOP). The cause of EPO insufficiency in AOP has been unclear, therefore current therapeutic options are transfusion and injection of recombinant human EPO. This report shows that the cause of insufficient EPO production in AOP is elevated renal oxygen levels due to poor oxygen consumption by immature tubules...
March 13, 2018: Scientific Reports
Ying Pang, Garima Gupta, Chunzhang Yang, Herui Wang, Thanh-Truc Huynh, Ziedulla Abdullaev, Svetlana D Pack, Melanie J Percy, Terence R J Lappin, Zhengping Zhuang, Karel Pacak
BACKGROUND: The role of the hypoxia signaling pathway in the pathogenesis of pheochromocytoma/paraganglioma (PPGL)-polycythemia syndrome has been elucidated. Novel somatic mutations in hypoxia-inducible factor type 2A (HIF2A) and germline mutations in prolyl hydroxylase type 1 and type 2 (PHD1 and PHD2) have been identified to cause upregulation of the hypoxia signaling pathway and its target genes including erythropoietin (EPO) and its receptor (EPOR). However, in a minority of patients presenting with this syndrome, the genetics and molecular pathogenesis remain unexplained...
March 13, 2018: BMC Cancer
Naoya Uchida, Juan J Haro-Mora, Selami Demirci, Atsushi Fujita, Lydia Raines, Matthew M Hsieh, John F Tisdale
A reliable cell line capable of robust in vitro erythroid differentiation would be useful to investigate red blood cell (RBC) biology and genetic strategies for RBC diseases. K562 cells are widely utilized for erythroid differentiation; however, current differentiation methods are insufficient to analyze globin proteins. In this study, we sought to improve erythroid differentiation from K562 cells to enable protein-level globin analysis. K562 cells were exposed to a variety of reagents including hemin, rapamycin, imatinib, and/or decitabine (known erythroid inducers), and cultured in basic culture media or erythropoietin-based differentiation media...
March 7, 2018: Experimental Hematology
Katsuhiro Yamanaka, Mohamed Eldeiry, Muhammad Aftab, Joshua Mares, Thomas J Ryan, Xianzhong Meng, Michael J Weyant, Joseph C Cleveland, David A Fullerton, T Brett Reece
BACKGROUND: Paraplegia remains the most feared complication of complex thoracoabdominal aortic intervention. Although erythropoietin (EPO) has demonstrated neuroprotective effects in spinal cord ischemia, it does not work until expression of the beta common receptor subunit of the EPO receptor (βcR) is induced by ischemia. We hypothesized that the βcR can be induced by diazoxide (DZ), amplifying the neuroprotective effects of EPO in spinal cord ischemia-reperfusion injury. METHODS: For the DZ time trial, adult male C57/BL6 mice received DZ (20 mg/kg) by oral gavage...
February 9, 2018: Journal of Thoracic and Cardiovascular Surgery
Ting Hong, Zhijuan Ge, Ran Meng, Hongdong Wang, Pengzi Zhang, Sunyinyan Tang, Jing Lu, Tianwei Gu, Dalong Zhu, Yan Bi
Erythropoietin (EPO), besides its stimulatory effect on erythropoiesis, is beneficial to insulin resistance and obesity. However, its role in hepatic steatosis remains unexplored. Activating autophagy seems a promising mechanism for improving fatty liver disease. The present study investigated the role of EPO in alleviating hepatic steatosis and sought to determine whether its function is mediated by the activation of autophagy. Here, we show that EPO decreased hepatic lipid content significantly in vivo and in vitro...
March 6, 2018: Biochimica et Biophysica Acta
Jill R Cherry-Bukowiec, Milo Engoren, Arek Wiktor, Krishnan Raghavendran, Lena M Napolitano
OBJECTIVE: Because anemia of inflammation is common in ICU patients and hepcidin is the key regulator of iron homeostasis, we examined time-dependent changes in hepcidin, erythropoietin, iron, and inflammatory markers in surgical ICU patients with anemia. DESIGN: Prospective single-center clinical noninterventional study. SETTING: Surgical ICUs; U.S. university hospital. PATIENTS: One hundred surgical adult ICU patients...
March 6, 2018: Critical Care Medicine
Dariusz Sitkowski, Zbigniew Szygula, Andrzej Pokrywka, Dariusz Turowski, Jadwiga Malczewska-Lenczowska
Interrelationships between physiological changes (Δ) in erythropoietin (EPO), plasma volume (PV), haemoglobin concentration ([Hb]), and total haemoglobin mass (tHb-mass) were examined in cyclists who trained in different altitudes. Regardless of differences in pattern of changes observed in three training locations, ΔEPO was correlated positively with ΔPV, negatively with Δ[Hb], and trivially with ΔtHb-mass. Δ[Hb] was negatively correlated with ΔPV. In the pooled data the Spearman's rank correlation coefficients were as follows: r = 0...
March 8, 2018: Research in Sports Medicine
Sandra E Juul, Bryan A Comstock, Patrick J Heagerty, Dennis E Mayock, Amy M Goodman, Stephanie Hauge, Fernando Gonzalez, Yvonne W Wu
BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) remains an important cause of neonatal death and frequently leads to significant long-term disability in survivors. Therapeutic hypothermia, while beneficial, still leaves many treated infants with lifelong disabilities. Adjunctive therapies are needed, and erythropoietin (Epo) has the potential to provide additional neuroprotection. OBJECTIVES: The aim of this study was to review the current incidence, mechanism of injury, and sequelae of HIE, and to describe a new phase III randomized, placebo-controlled trial of Epo neuroprotection in term and near-term infants with moderate to severe HIE treated with therapeutic hypothermia...
March 7, 2018: Neonatology
Jakub Zmajkovic, Pontus Lundberg, Ronny Nienhold, Maria L Torgersen, Anders Sundan, Anders Waage, Radek C Skoda
Familial erythrocytosis with elevated erythropoietin levels is frequently caused by mutations in genes that regulate oxygen-dependent transcription of the gene encoding erythropoietin ( EPO). We identified a mutation in EPO that cosegregated with disease with a logarithm of the odds (LOD) score of 3.3 in a family with autosomal dominant erythrocytosis. This mutation, a single-nucleotide deletion (c.32delG), introduces a frameshift in exon 2 that interrupts translation of the main EPO messenger RNA (mRNA) transcript but initiates excess production of erythropoietin from what is normally a noncoding EPO mRNA transcribed from an alternative promoter located in intron 1...
March 8, 2018: New England Journal of Medicine
Giuliano Ramadori, Patrizia Bosio, Federico Moriconi, Ihtzaz A Malik
BACKGROUND: After orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC), recurrent HCC mostly develops within 2 years. All cases of de novo HCC described so far occurred later than 2 years after OLT. Prevention of post-transplantation HCC has usually been tried to achieve by curing or controlling recurrent liver disease. This has been rationale for treatment with interferon (IFN)/ribavirin of HCV-recurrence in patients after OLT, transplanted for advanced HCV-induced liver disease and/or HCC...
March 6, 2018: BMC Cancer
Friederike Grosse-Holz, Luisa Madeira, Muhammad Awais Zahid, Molly Songer, Jiorgos Kourelis, Mary Fesenko, Sabrina Ninck, Farnusch Kaschani, Markus Kaiser, Renier A L van der Hoorn
Agroinfiltrated Nicotiana benthamiana is a flexible and scalable platform for recombinant protein (RP) production, but its great potential is hampered by plant proteases that degrade RPs. Here, we tested 29 candidate protease inhibitors (PIs) in agroinfiltrated N. benthamiana leaves for enhancing accumulation of three unrelated RPs: glycoenzyme α-Galactosidase; glycohormone erythropoietin (EPO); and IgG antibody VRC01. Of the previously described PIs enhancing RP accumulation, we found only cystatin SlCYS8 to be effective...
March 6, 2018: Plant Biotechnology Journal
Xiao-Fei Bai, Yong-Kai Gao
BACKGROUND: This study aimed to explore the efficacy and safety of recombinant human erythropoietin (RHE) for the treatment of severe traumatic brain injury (STBI). METHODS: One hundred and twenty eligible patients with STBI were randomly divided into an intervention group or a control group equally. Patients in the intervention group received RHE. The participants in the control group received 0.9% saline. The outcome measurements included the Glasgow Outcome Scale (GOS) scores, mortality, and any adverse events...
January 2018: Medicine (Baltimore)
Shaoyun Zhang, Qiang Huang, Bin Xu, Jun Ma, Guorui Cao, Fuxing Pei
Little has been published on blood management in total hip and knee arthroplasty (THA and TKA, respectively) patients focusing on both hematopoiesis and hemostasis. Our aim was to explore the effectiveness and safety of an optimized blood management program in THA and TKA patients in a large, single-center, retrospective study.We retrospectively reviewed consecutive primary unilateral THA and TKA patients' data at our institution through the National Health Database. They were divided into 3 groups according to an optimized blood management program: group A-combined use of intravenous and topical tranexamic acid (TXA); group B-use of recombinant human erythropoietin (rHuEPO) and iron supplements in addition to treatments in group A; group C-use of additional multiple boluses of TXA in addition to treatments in group B...
January 2018: Medicine (Baltimore)
Niels J Aachmann-Andersen, Soren J Christensen, Kristian Lisbjerg, Peter Oturai, Pär I Johansson, Niels-Henrik Holstein-Rathlou, Niels V Olsen
The effect of recombinant erythropoietin (rhEPO) on renal and systemic hemodynamics was evaluated in a randomized double-blinded, cross-over study. Sixteen healthy subjects were tested with placebo, or low-dose rhEPO for 2 weeks, or high-dose rhEPO for 3 days. Subjects refrained from excessive salt intake, according to instructions from a dietitian. Renal clearance studies were done for measurements of renal plasma flow, glomerular filtration rate (GFR) and the segmentel tubular handling of sodium and water (lithium clearance)...
March 2018: Physiological Reports
Michele F Eisenga, Lyanne M Kieneker, Daan J Touw, Ilja M Nolte, Peter van der Meer, Gerwin Huls, Carlo A J M Gaillard, Stephan J L Bakker
Cigarette smoking continues to be one of the major risk factors for increased morbidity and mortality worldwide. Among many adverse health effects, smoking can induce erythrocytosis, which is commonly believed to result from elevated serum erythropoietin (EPO) levels. Currently, however, this notion is only alleged, without data available to substantiate it. Hence, we analyzed data from the Prevention of Renal and Vascular End-Stage Disease study, a prospective population-based cohort study. Smoking behavior was quantified as number of cigarettes smoked per day and as 24-hour urinary cotinine excretion levels, an objective and quantitative measure of nicotine exposure...
March 2018: Mayo Clinic Proceedings
Ben Cowper, Xiang Li, Lei Yu, Yong Zhou, W H Fan, C M Rao
Recombinant, human, erythropoietin (rhEPO) is a glycoprotein hormone which is prescribed throughout the world to treat anaemia caused by chronic kidney disease or chemotherapy. rhEPO is at the forefront of the recent emergence of biosimilar medicines, with numerous products now available worldwide. Due to its complex glycosylation profile, which has a crucial influence upon biological activity, therapeutic rhEPO preparations must be closely monitored to ensure consistency, safety and efficacy. Here, we have compared twelve rhEPO preparations from eleven manufacturers in China and one in Japan, measuring in vivo biological activity and exploring its relationship with glycosylation through sialic acid content determination, isoform distribution via capillary electrophoresis (CE), O-glycan profiling, and N-glycan mapping using a novel anion-exchange/hydrophilic interaction chromatography-mass spectrometry (AEX/HILIC-MS) approach...
February 24, 2018: Journal of Pharmaceutical and Biomedical Analysis
L Martin, N Zouhiri, M Audran, A Marchand
New therapeutic proteins that trap circulating members of the TGF beta superfamily (activins and growth differentiation factors) show promising effects on erythropoiesis and muscular growth. They are dimeric recombinant fusion proteins composed of the extracellular domain of a human activin receptor (ActRIIA or IIB) linked to the Fc part of human IgG1. Sotatercept (ActRIIA-Fc) and Luspatercept (a modified ActRIIB-Fc) in particular are now in phase 2/3 of clinical trials against anemia and included in the prohibited list established by the World Anti-Doping Agency...
March 2, 2018: Drug Testing and Analysis
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