scholarly journals Transcriptomic Markers of Recombinant Human Erythropoietin Micro-Dosing in Thoroughbred Horses

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1874
Author(s):  
Anna R. Dahlgren ◽  
Heather K. Knych ◽  
Rick M. Arthur ◽  
Blythe P. Durbin-Johnson ◽  
Carrie J. Finno
Keyword(s):  
Recombinant Human Erythropoietin ◽  
Mononuclear Cells ◽  
Cell Mass ◽  
Arterial Oxygen ◽  
Horse Racing ◽  
Peripheral Blood Mononuclear ◽  
Arterial Oxygen Content ◽  
Human Erythropoietin ◽  
Thoroughbred Horses ◽  
Important Concern

Recombinant human erythropoietin (rHuEPO) is a well-known performance enhancing drug in human athletes, and there is anecdotal evidence of it being used in horse racing for the same purpose. rHuEPO, like endogenous EPO, increases arterial oxygen content and thus aerobic power. Micro-doping, or injecting smaller doses over a longer period of time, has become an important concern in both human and equine athletics since it is more difficult to detect. Horses offer an additional challenge of a contractile spleen, thus large changes in the red blood cell mass occur naturally. To address the challenge of detecting rHuEPO doping in horse racing, we determined the transcriptomic effects of rHuEPO micro-dosing over seven weeks in exercised Thoroughbreds. RNA-sequencing of peripheral blood mononuclear cells isolated at several time points throughout the study identified three transcripts (C13H16orf54, PUM2 and CHTOP) that were significantly (PFDR < 0.05) different between the treatment groups across two or three time point comparisons. PUM2 and CHTOP play a role in erythropoiesis while not much is known about C13H16orf54, but it is primarily expressed in whole blood. However, gene expression differences were not large enough to detect via RT-qPCR, thereby precluding their utility as biomarkers of micro-doping.

Stimulation of Interleukin-1 ß Production may be Involved in Unresponsiveness to Erythropoietin Therapy

1996 ◽  
Vol 19 (11) ◽  
pp. 633-637 ◽  
Author(s):  
A. Takemasa ◽  
N. Yorioka ◽  
M. Yamakido
Keyword(s):  
Recombinant Human Erythropoietin ◽  
Mononuclear Cells ◽  
Interleukin 1 ◽  
Poor Response ◽  
Dialysis Patients ◽  
Peripheral Blood Mononuclear ◽  
Human Erythropoietin ◽  
Significant Difference ◽  
Blood Mononuclear Cells ◽  
Stimulation Of

Recombinant human erythropoietin (rHuEPO) can dramatically improve anemia in dialysis patients, but about 20% of patients show a poor response to this agent. It has been reported that cytokines, including interleukin (IL)-1ß, may inhibit the maturation of erythrocytes. To investigate the mechanisms of unresponsiveness to rHuEPO, we isolated peripheral blood mononuclear cells from 12 patients on continuous ambulatory peritoneal dialysis who were receiving maintenance rHuEPO therapy for renal anemia. Cells were cultured with rHuEPO and IL-1 ß production was assessed. In the six patients who did not respond to rHuEPO therapy, there was a marked increase in IL-1 ß during culture with rHuEPO. In contrast, the addition of rHuEPO to cultures of cells from the six responding patients caused little increase in IL-1 ß, and there was a significant difference between the two groups. Induction of IL-1 ß by rHuEPO may be one cause of persistent anemia in dialysis patients.

Investigation of the Influenza-Like Symptoms Associated with Recombinant Human Erythropoietin Therapy

1997 ◽  
Vol 25 (3) ◽  
pp. 127-134 ◽  
Author(s):  
A Takemasa ◽  
N Yorioka ◽  
M Yamakido
Keyword(s):  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Recombinant Human Erythropoietin ◽  
Mononuclear Cells ◽  
Interleukin 1 ◽  
Tumour Necrosis Factor Α ◽  
Peripheral Blood Mononuclear ◽  
Human Erythropoietin ◽  
Factor Α ◽  
Necrosis Factor

The mechanism by which fever and influenza-like symptoms occur, after the administration of recombinant human erythropoietin (rHuEPO) to patients on continuous ambulatory peritoneal dialysis, was investigated. Peripheral blood mononuclear cells, obtained from two patients with fever and/or influenza-like symptoms related to the administration of rHuEPO for the treatment of anaemia were cultured with or without rHuEPO (100, 200, and 300 U/ml). Production of interleukin-1 β and tumour necrosis factor-α was higher in cultures with rHuEPO than in cultures without rHuEPO, although the dose relationships were not clear. These findings suggest that increased production of interleukin-1 β and tumour necrosis factor-α, induced by administration of rHuEPO, may cause fever and influenza-like smptoms.

scholarly journals Changes in the kinetics and biopotency of luteinizing hormone in hemodialyzed men during treatment with recombinant human erythropoietin.

1994 ◽  
Vol 5 (5) ◽  
pp. 1208-1215
Author(s):  
F Schaefer ◽  
B van Kaick ◽  
J D Veldhuis ◽  
G Stein ◽  
K Schärer ◽  
...  
Keyword(s):  
Luteinizing Hormone ◽  
Half Life ◽  
Recombinant Human Erythropoietin ◽  
Cell Mass ◽  
Elimination Kinetics ◽  
Deconvolution Analysis ◽  
Human Erythropoietin ◽  
Change In Mean ◽  
Plasma Half Life

To investigate the effect of recombinant human erythropoietin (rh-EPO) on the hypothalamo-pituitary-gonadal axis in end-stage renal failure, plasma luteinizing hormone (LH) concentration release was assessed by frequent blood sampling (every 10 min), both during an 8-h baseline period and after stimulation with an iv bolus of gonadotropin-releasing hormone (GnRH). Seven adult hemodialyzed men were studied before and after partial correction of anemia by rh-EPO treatment. LH was determined by an in vitro Leydig cell bioassay (bio-LH) and a highly sensitive immunoradiometric assay. Pulsatile bio-LH secretion and clearance characteristics were assessed by multiple-parameter deconvolution analysis. Although the rh-EPO treatment did not lead to a change in average concentrations of plasma bio-LH, the mass of hormone released per secretory burst more than doubled, and the estimated bio-LH production rate increased from 8.8 +/- 2.3 to 15.6 +/- 5.2 IU/L per hour (P = 0.05). The lack of change in mean plasma bio-LH is explained by a simultaneous decrease in plasma half-life from 106 +/- 27 to 67 +/- 19 min (P < 0.02). The decrease in the plasma half-life of bio-LH was closely associated with the rise in hematocrit, suggesting an effect of the increased red blood cell mass on LH distribution space and elimination kinetics. As a consequence of the changes in hormone kinetics, the incremental amplitudes of the plasma concentration pulses of bio-LH increased from 112 to 121% of nadir levels (P < 0.05), resulting in a more distinctly pulsatile pattern of hormone signals.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac limitation to maximal oxygen transport and changes in components after jogging across the US

1975 ◽  
Vol 39 (6) ◽  
pp. 958-964 ◽  
Author(s):  
R. A. Bruce ◽  
F. Kusumi ◽  
B. H. Culver ◽  
J. Butler
Keyword(s):  
Stroke Volume ◽  
Oxygen Transport ◽  
Cell Mass ◽  
Young Male ◽  
The United States ◽  
Systemic Arterial Pressure ◽  
Arterial Oxygen ◽  
Total Blood ◽  
Male Adult ◽  
Arterial Oxygen Content

Observations were made before and 3–5 days after prolonged endurance jogging an average of 42 miles/day, 6 days/wk for 2.5 mo by a young male adult who voluntarily initiated a run across the United States. Both arterial PO2 and lactic acid increased. In each instance, the first limitation in circulatory delivery of oxygen was a plateau in stroke volume and cardiac output. Afterward, pulse deficit and systemic arterial pressure fell with exercise and heart rate accelerated. Although there was no change in oxygen transport (Q X CAO2), a reduction in stroke volume was exactly balanced by a rise in arterial oxygen content. Vital capacity, residual volume, and total lung capacity and diffusion capacity for carbon monoxide, hematocrit, and red cell mass increased, while plasma volume diminished and heart size and total blood volume were unchanged.

scholarly journals Improvement of mouse beta-thalassemia by recombinant human erythropoietin

Blood ◽  
1991 ◽  
Vol 78 (6) ◽  
pp. 1596-1602 ◽  
Author(s):  
K Leroy-Viard ◽  
P Rouyer-Fessard ◽  
Y Beuzard
Keyword(s):  
Recombinant Human Erythropoietin ◽  
Cell Mass ◽  
Thiol Group ◽  
Beta Thalassemia ◽  
Globin Chain ◽  
Trichloracetic Acid ◽  
Human Erythropoietin ◽  
Alpha Globin ◽  
Chain Imbalance ◽  
Chain Synthesis

Homozygous beta thalassemic mice received 50 U (1,660 U/kg) of recombinant human erythropoietin (rhEpo) 5 days a week for 2 weeks. Hemoglobin increased from 9.2 +/- 0.6 g/dL to 10.5 +/- 0.4 g/dL (P = .002) and hematocrit increased from 29.2% +/- 0.9% to 34.1% +/- 1.9% (P = .0014). The beta minor/alpha globin chain synthesis ratio increased slightly but significantly between day -4 (0.75 +/- 0.07) and day 4 (0.81 +/- 0.04) (P = .01) and reached a minimum ratio (0.67 +/- 0.03) on day 15 (P = .001), being parallel to reticulocyte counts and to the incorporated trichloracetic acid (TCA)-insoluble radioactivity, therefore parallel to the erythropoietic output in thalassemic mice, as in normal mice. Erythrocyte defects were improved in beta thalassemic mice treated by rhEpo: membrane-associated alpha globin was significantly decreased (P less than .01), thiol group reactivity of ankyrin was significantly improved (P less than .05), spectrin alterations were reduced, and deformability of mouse thalassemic red blood cells was normalized. These results provide experimental criteria for modulating globin chain imbalance necessary for the therapy of human beta thalassemia intermedia, and suggest that rhEpo might be of interest to improve the red blood cell mass and reduce erythrocyte alterations in this disease.

scholarly journals Avoidance of Allogeneic Blood Transfusions by Treatment With Epoetin Beta (Recombinant Human Erythropoietin) in Patients Undergoing Open-Heart Surgery

Blood ◽  
1997 ◽  
Vol 89 (2) ◽  
pp. 411-418 ◽  
Author(s):  
Olaf Sowade ◽  
Harry Warnke ◽  
Paul Scigalla ◽  
Birgit Sowade ◽  
Werner Franke ◽  
...  
Keyword(s):  
Recombinant Human Erythropoietin ◽  
Heart Surgery ◽  
Cell Mass ◽  
Open Heart Surgery ◽  
Allogeneic Blood ◽  
Blood Transfusions ◽  
Open Heart ◽  
Epoetin Beta ◽  
Human Erythropoietin ◽  
The Mean

Abstract In a double-blind, randomized, placebo-controlled trial, we evaluated the ability of epoetin beta (recombinant human erythropoietin) to avoid allogeneic blood transfusions (ABT) and the associated risks in patients undergoing primary elective open-heart surgery and in whom autologous blood donation (ABD) was contraindicated. Seventy-six patients overall were enrolled onto the trial and were randomly assigned to the two treatment groups, 5 × 500 U/kg body weight (BW) epoetin beta or placebo intravenously over 14 days preoperatively. All patients received 300 mg Fe2+ orally per day during the treatment period. Preoperatively, the mean hemoglobin increase was 1.50 g/dL greater in epoetin beta patients than in placebo patients (95% confidence interval, 1.10 to 1.90 g/dL), allowing a rapid return to the baseline value by the seventh postoperative day in most epoetin beta patients. The mean volume of blood collected by intraoperative isovolemic hemodilution was 562 mL (red blood cell mass, 274 mL) in the epoetin beta group and 218 mL (red blood cell mass, 94 mL) in the placebo group, respectively. Only four patients (11%) in the epoetin beta group received an ABT, compared with 19 (53%) in the placebo group (P = .0003). Epoetin beta was most useful in patients with a perioperative blood loss greater than 750 mL, in those with a baseline hematocrit value less than 0.42, and in those aged ≥60 years. The iron supplementation proved adequate despite the fact that a significant decrease in ferritin (median, 48.1%) and transferrin saturation (median, 40.5%) was observed in epoetin beta patients preoperatively. No influence of epoetin beta therapy on blood pressure, laboratory safety variables, or the frequency of specific adverse events was observed. Intravenous epoetin beta treatment of 5 × 500 U/kg BW in combination with 300 mg Fe2+ orally per day administered over 14 days preoperatively is an adequate therapy for increasing mean hemoglobin levels by approximately 1.50 g/dL and reducing the allogeneic blood requirement in patients undergoing elective open-heart surgery and in whom ABD is contraindicated.

scholarly journals Improvement of mouse beta-thalassemia by recombinant human erythropoietin

Blood ◽  
1991 ◽  
Vol 78 (6) ◽  
pp. 1596-1602 ◽  
Author(s):  
K Leroy-Viard ◽  
P Rouyer-Fessard ◽  
Y Beuzard
Keyword(s):  
Recombinant Human Erythropoietin ◽  
Cell Mass ◽  
Thiol Group ◽  
Beta Thalassemia ◽  
Globin Chain ◽  
Trichloracetic Acid ◽  
Human Erythropoietin ◽  
Alpha Globin ◽  
Chain Imbalance ◽  
Chain Synthesis

Abstract Homozygous beta thalassemic mice received 50 U (1,660 U/kg) of recombinant human erythropoietin (rhEpo) 5 days a week for 2 weeks. Hemoglobin increased from 9.2 +/- 0.6 g/dL to 10.5 +/- 0.4 g/dL (P = .002) and hematocrit increased from 29.2% +/- 0.9% to 34.1% +/- 1.9% (P = .0014). The beta minor/alpha globin chain synthesis ratio increased slightly but significantly between day -4 (0.75 +/- 0.07) and day 4 (0.81 +/- 0.04) (P = .01) and reached a minimum ratio (0.67 +/- 0.03) on day 15 (P = .001), being parallel to reticulocyte counts and to the incorporated trichloracetic acid (TCA)-insoluble radioactivity, therefore parallel to the erythropoietic output in thalassemic mice, as in normal mice. Erythrocyte defects were improved in beta thalassemic mice treated by rhEpo: membrane-associated alpha globin was significantly decreased (P less than .01), thiol group reactivity of ankyrin was significantly improved (P less than .05), spectrin alterations were reduced, and deformability of mouse thalassemic red blood cells was normalized. These results provide experimental criteria for modulating globin chain imbalance necessary for the therapy of human beta thalassemia intermedia, and suggest that rhEpo might be of interest to improve the red blood cell mass and reduce erythrocyte alterations in this disease.

scholarly journals Antigen-specific immunotherapy combined with a regenerative drug in the treatment of experimental type 1 diabetes

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Adrian Villalba ◽  
Silvia Rodriguez-Fernandez ◽  
David Perna-Barrull ◽  
Rosa-Maria Ampudia ◽  
Laia Gomez-Muñoz ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Mononuclear Cells ◽  
Combined Therapy ◽  
Cell Mass ◽  
Β Cell ◽  
Membrane Expression ◽  
Peripheral Blood Mononuclear ◽  
Autoimmune Attack

Abstract Type 1 diabetes is an autoimmune disease caused by the destruction of the insulin-producing β-cells. To revert type 1 diabetes, the suppression of the autoimmune attack should be combined with a β-cell replacement strategy. It has been previously demonstrated that liraglutide, a glucagon-like peptide-1 receptor agonist, restores β-cell mass in type 1 diabetes, via α-cell transdifferentiation and neogenesis. We report here that treatment with liraglutide does not prevent type 1 diabetes in the spontaneous non-obese diabetic (NOD) mouse model, but it tends to reduce leukocytic islet infiltration. However, in combination with an immunotherapy based on tolerogenic liposomes, it is effective in ameliorating hyperglycaemia in diabetic NOD mice. Importantly, liraglutide is not detrimental for the tolerogenic effect that liposomes exert on dendritic cells from patients with type 1 diabetes in terms of membrane expression of molecules involved in antigen presentation, immunoregulation and activation. Moreover, the in vivo effect of the combined therapy was tested in mice humanised with peripheral blood mononuclear cells from patients with type 1 diabetes, showing no adverse effects in leukocyte subsets. In conclusion, the combination therapy with liraglutide and a liposome-based immunotherapy is a promising candidate strategy for type 1 diabetes.

scholarly journals Multi-parameter immune profiling of peripheral blood mononuclear cells by multiplexed single-cell mass cytometry in patients with early multiple sclerosis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Chotima Böttcher ◽  
Camila Fernández-Zapata ◽  
Stephan Schlickeiser ◽  
Desiree Kunkel ◽  
Axel R. Schulz ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Cell Mass ◽  
Healthy Controls ◽  
Mass Cytometry ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

AbstractMultiple sclerosis (MS) is an inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS). Studies in rodent models demonstrated an association of CNS-infiltrating monocyte-derived macrophages with disease severity. However, little is known about humans. Here, we performed an exploratory analysis of peripheral blood mononuclear cells (PBMCs) isolated from healthy controls and drug-naïve patients with early MS using multiplexed single-cell mass cytometry and algorithm-based data analysis. Two antibody panels comprising a total of 64 antibodies were designed to comprehensively analyse diverse immune cell populations, with particular emphasis on monocytes. PBMC composition and marker expression were overall similar between the groups. However, an increased abundance of CCR7+ and IL-6+ T cells was detected in early MS-PBMCs, whereas NFAT1hiT-bethiCD4+ T cells were decreased. Similarly, we detected changes in the subset composition of the CCR7+ and MIPβhi HLA-DR+ lymphocyte compartment. Only mild alterations were detected in monocytes/myeloid cells of patients with early MS, namely a decreased abundance of CD141hiIRF8hiCXCR3+CD68− dendritic cells. Unlike in Crohn’s disease, no significant differences were found in the monocyte fraction of patients with early MS compared to healthy controls. This study provides a valuable resource for future studies designed to characterise and target diverse PBMC subsets in MS.

Sign in / Sign up

Export Citation Format

Share Document