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Figure 1. Effects of repeated administration of very low to low doses of recombinant human erythropoietin on total hemoglobin mass, erythropoietin, erythroferrone
Low-dose erythropoietin induces erythroferrone
B
C
D
A
), determined at baseline (Pre) and 72 h after the last of the six injections (Post) of placebo (n=7), recombinant human mass
and hepcidin. (A) Total hemoglobin mass (Hb
erythropoietin (rhEpo) 20 IU/kg (micro-dose) (n=7) or rhEpo 50 IU/kg (low dose) (n=8). ANOVA for a significant time × treatment interaction (P=0.049). *Indicates a sig-
values are available in Online Supplementary Figure S1. (B-D) Serum concentrations of erythropoietin (B), erythroferrone (ln transformed, n=7 for the placebo condition) (C) and hepcidin (ln transformed) (D) before, during and after six injections of placebo (n=8), micro-dose rhEpo (n=8) or low-dose rhEpo (n=8). Vertical dotted lines indicate injections. Baselines are means from duplicate blood samples collected on separated days. Blood sampling was repeatedly performed at 24 h (2 occurrences), 48 h (4 occurrences) and 72 h (2 occurrences) after an injection. Additional samples were obtained at 7 and 14 days after the last injection. Numbers above the abscissa line (i.e., 24, 48, 72, 7d and 14d) indicate these sam- pling times, respectively. Data are means ± standard deviations. For each panel, the inserted table reports estimated marginal means ± standard errors and P-values for the effect of the group (placebo, micro-dose, low dose), the occurrence (i.e., the number of samples at 24 h, 48 h, 72 h, 7 days and 14 days, from 1 to 4) and the group × occurrence (G × O) interaction. Multiple comparisons between groups at 24 h, 48 h or 72 h are reported in each table, *Denotes a difference from placebo and ‡denotes a difference from micro-dose rhEPO (see the Online Supplementary Material, Statistical analysis section). Epo: erythropoietin; ERFE: erythroferrone; PLA: place-
nificant difference between low-dose rhEpo and placebo. Data are means ± standard deviations. Individual Hb mass
bo. EPO20: recombinant human erythropoietin 20 IU/kg; EPO50: recombinant human erythropoietin 50 IU/kg.
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