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EPO Concentrations (epo + concentration)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Regulation of erythropoietin production

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2005
K.-U. Eckardt
Abstract The glycoprotein hormone erythropoietin (EPO) is an essential growth and survival factor for erythroid progenitor cells, and the rate of red blood cell production is normally determined by the serum EPO concentration. EPO production is inversely related to oxygen availability, so that an effective feedback loop is established, which controls erythropoiesis. Since recombinant EPO became available as an effective therapeutic agent, significant progress has also been made in understanding the basis of this feedback control. The main determinant of EPO synthesis is the transcriptional activity of its gene in liver and kidneys, which is related to local oxygen tensions. This control is achieved by hypoxia-inducible transcription factors (HIF), consisting of a constitutive ,-subunit and one of two alternative oxygen-regulated HIF, subunits (HIF-1, and HIF-2,). In the presence of oxygen (normoxia) the HIF, subunits are hydroxylated, which targets them for proteasomal degradation. Under hypoxia, because of the lack of molecular oxygen, HIF cannot be hydroxylated and is thereby stabilized. Although HIF-1, was the first transcription factor identified through its ability to bind to an enhancer sequence of the EPO gene, more recent evidence suggests that HIF-2, is responsible for the regulation of EPO. Although EPO is a prime example for an oxygen- regulated gene, the role of the HIF system goes far beyond the regulation of EPO, because it operates widely in almost all cells and controls a broad transcriptional response to hypoxia, including genes involved in cell metabolism, angiogenesis and vascular tone. Further evidence suggests that apart from its effect as an erythropoietic hormone EPO acts as a paracrine, tissue-protective protein in the brain and possibly also in other organs. [source]

Hydroxyurea therapy increases plasma erythropoietin in patients with essential thrombocythaemia or polycythaemia vera

INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 4 2006
P. JOHANSSON
Summary The determination of serum/plasma erythropoietin (EPO) concentration has gained widespread use in the diagnosis of polycythaemia vera (PV). A reduced EPO concentration in a newly diagnosed essential thrombocythaemia (ET) seems to be a risk factor for thromboembolic events. In this study plasma EPO concentration was determined before and after initiated hydroxyurea (HU) therapy, 14 patients with PV or ET were included. After 1 month on HU therapy 11 of 14 patients had increased their EPO concentration compared with prior to medication. The plasma EPO was increased in all, except one patient, after 4 months HU therapy. If EPO is incorporated in the diagnostic or prognostic procedures it should be determined before myelosuppressive therapy is initiated. [source]

Erythropoietin production rate in phlebotomy-induced acute anemia

BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 9 2004
N.H. Al-Huniti
Abstract Objective. To estimate the rate of erythropoietin (EPO) production under physiological, conditions and to examine the regulatory mechanism of EPO production in response to acute phlebotomy-induced anemia. Methods. Six sheep each underwent two phlebotomies in which the hemoglobin (Hb) was reduced to 3,4 g/dl over 4,5 h. The EPO plasma level, reticulocytes, Hb and EPO clearance were followed by frequent blood sampling. The EPO production rate was determined by a semi-parametric method based on a disposition decomposition analysis that accounts for the nonlinear disposition kinetics of EPO and corrects for time-dependent changes in the clearance. Results. The controlled drop in hemoglobin resulted in an abrupt increase in the plasma EPO concentration (peak level 812 ± 40 mU/ml, mean ± CV%) that was followed by a rapid drop 2,4 days after the phlebotomy at a time when the sheep were still anemic (Hb = 4.3 ± 16 g/dl). The EPO production rate at baseline was 43 ± 52 U/day/kg and the amounts of EPO produced over an 8 day period resulting from the first and second phlebotomy were 2927 ± 40 U/kg and 3012 ± 31 U/kg, respectively. Conclusions. The rapid reduction in the EPO plasma level observed 2,4 days following the phlebotomy cannot be explained solely by the increase in EPO clearance but also by a reduction in EPO production. Copyright © 2004 John Wiley & Sons, Ltd. [source]

A sample distribution programme for erythropoietin

INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 4 2006
J. T. MARSDEN
Summary A survey was sent to laboratories participating in the United Kingdom External Quality Assessment Service (UKNEQAS) Haematinics Scheme about the measurement of serum erythropoietin (EPO). Six laboratories, from a total of 120 that returned the survey, were measuring serum EPO concentrations by commercially available immunoassays on site in the United Kingdom. The workload of the laboratories varied from up to 100 specimens per month to more than 100 specimens analysed per week. All laboratories included control material in the assays and none of the laboratories was participating in an external quality assessment scheme for serum EPO. Four laboratories agreed to take part in the first sample distribution programme, with five and six laboratories participating in distributions 2 and 3 respectively. The results from eight kits were compared from the three distributions over a 2-year period. The serum EPO concentrations for the methods showed some variation across the range of 2.9,200 U/l when the serum EPO concentrations for each method were compared with the whole method mean. The results from this scheme have identified a role for an external quality assessment scheme for serum EPO measurements. [source]

Nucleated red blood cell counts and erythropoietin levels in high-risk neonates

PEDIATRICS INTERNATIONAL, Issue 6 2002
Ülfet Vatansever
Abstract Background: The presence of increased numbers of nucleated red blood cells (NRBC) and increased levels of erythropoietin (EPO) in the circulation of neonates has been associated with states of relative hypoxia. The aim of this study is to assess the pattern of NRBC counts and EPO levels in a group of high-risk neonates under stress conditions and determine the short-term outcome for these babies by using these parameters. Methods: There were 69 high-risk neonates; 14 intrauterine growth retarded (IUGR), 25 preterm infants, 18 term infants with asphyxia and 12 infants of diabetic mothers. Control groups included healthy, term infants delivered either vaginally (n = 18) or with cesarean section (n = 19). Three blood samples were obtained from each infant within 12 h (initial), 3 days and 7 days after birth to measure NRBC counts and EPO levels. Neonatal and short-term outcomes at 3 and 6 months of age were determined. Results: There was no significant difference among the groups with regard to the initial serum EPO concentrations. The initial NRBC counts were significantly lower in the control groups compared with the study groups (P = 0.002). While there was no significant difference between patients with good and poor outcome in terms of EPO concentrations of initial samples, a significant difference existed in terms of NRBC counts (P = 0.038). Conclusions: Both serum EPO level and NRBC count provide limited clinical benefit in the detection of pathological conditions of the neonatal period, but NRBC count determination seems to be especially helpful in predicting short-term neurodevelopmental outcome. [source]

A ,bottom-up' approach for endo-PK/PD analysis

BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 7 2006
S. Neelakantan
Abstract A ,bottom-up' PK/PD analysis approach employing system analysis principles of convolution/deconvolution and special nonparametric estimation procedures is presented to resolve the complex ,endo-PK/PD' of the endogenous form of recombinant drugs using erythropoietin (EPO) as an example. A novel cellular deconvolution algorithm is presented that facilitates the identification of the functional relationship between the variables involved in EPO's complex PK/PD. Five sheep each underwent two phlebotomies spaced 4,6 weeks apart when their hemoglobin levels were reduced from 12 g/dl to 3,4 g/dl. EPO levels and reticulocyte counts were frequently sampled. The data were analysed using end-constrained cubic splines. The rate of reticulocyte production was determined using the novel deconvolution methodology. The erythroid progenitor cells activation rate by EPO was estimated from the reticulocyte production rate using a lag-time parameter which determines the delay in the reticulocyte appearance in the blood relative to the activation of erythroid progenitors. Hysteresis minimization combined with cellular deconvolution was employed to determine the population PK/PD transduction function relating the progenitor activation rate to EPO concentrations in a nonparametric manner without assuming a specific structure. The proposed approach provides a rational informative starting point for developing parametric PK/PD models to resolve the complex endo-PK/PD of recombinant drugs. Copyright © 2006 John Wiley & Sons, Ltd. [source]

Local release of eosinophil peroxidase following segmental allergen provocation in asthma

CLINICAL & EXPERIMENTAL ALLERGY, Issue 3 2003
V. J. Erpenbeck
Summary Background Eosinophil peroxidase (EPO) is an eosinophilic basic protein, which leads to increased permeability and damage of bronchial epithelial cells in asthma. Objective As little is known about its local expression and release in humans the intracellular expression in lung and peripheral eosinophils and the concentrations of EPO in bronchoalveolar lavage (BAL) fluid and serum was investigated in patients with asthma. Methods Twelve mild atopic asthmatic and nine control subjects underwent segmental sham and allergen challenge. EPO concentrations in BAL fluid and serum were determined by immunoassay and flow cytometry was used to determine the intracellular expression of EPO in BAL-derived and peripheral eosinophils. Results In asthmatic patients a large increase in BAL eosinophils , total cells: median 9.5 × 106 (range: 0.5 to 455.0 × 106); relative: 38% (1 to 91%) , was detectable 24 h following allergen challenge, but peripheral blood eosinophil counts did not change. Concentrations of EPO in BAL fluid increased from 1 µg/L (1.0 to 6.8 µg/L) to 42 µg/L (5.6 to 379.6 µg/L; P < 0.01) after allergen but not after saline challenge (1.5 µg/L; 1.0 to 21.9 µg/L), whereas in control subjects all measurements were below the detection limit. Serum concentrations of EPO increased slightly from 18.3 µg/L (3.0 to 56.8 µg/L) to 27 µg/L (3.8 to 133.9 µg/L; P < 0.05) 24 h after allergen challenge in asthmatic patients. Furthermore, the intracellular expression of EPO (measured as mean fluorescence intensity) was decreased in BAL eosinophils compared with blood eosinophils (mean fluorescence intensity 29 (7 to 71) vs. 48 (20 to 85); P < 0.01) after allergen challenge. Conclusion The finding of increased EPO concentrations in the BAL fluid and decreased intracellular EPO expression in pulmonary eosinophils of asthmatic patients reflects the allergen-triggered release of EPO into the bronchial space. [source]