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Erythropoietin Restores C-Fiber Function and Prevents Pressure Ulcer Formation in Diabetic Mice
Claire Demiot, Vincent Sarrazy, James Javellaud, Loriane Gourloi, Laurent Botelle, Nicole Oudart, Jean-Michel Achard Journal of Investigative Dermatology Volume 131, Issue 11, Pages (November 2011) DOI: /jid Copyright © 2011 The Society for Investigative Dermatology, Inc Terms and Conditions
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Figure 1 Effect of erythropoietin (EPO) on skin neuropathy. (a) Randall–Sellito tail pressure test. Mechanical withdrawal thresholds in control and diabetic mice treated or not treated with recombinant human erythropoietin (rhEPO). **P<0.01 versus respective control mice; †P<0.05 versus diabetic mice; n=10 in each group. (b) Immunohistochemical labeling of protein gene product 9.5 (PGP 9.5)-positive cutaneous axons (white arrows) from the flank region. The dermis of control skin contains horizontal PGP 9.5-positive nerve bundles. In contrast, diabetes causes an obvious decrease in dermal and epidermal innervations. RhEPO restores general innervation. Original magnification × 200; bar (white)=100 μm; “F” denotes hair follicles. (c) Abundance of PGP 9.5-positive axons in the skin from the flank. The percentage of skin area occupied by immunopositive axons is shown. **P<0.01 versus respective control mice; †P<0.05 versus diabetic mice; n=12 in each group. Journal of Investigative Dermatology , DOI: ( /jid ) Copyright © 2011 The Society for Investigative Dermatology, Inc Terms and Conditions
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Figure 2 Effect of erythropoietin (EPO) on skin microcirculation reactivity alteration. (a) Endothelium-dependent vasodilation. Maximal percentage of vasodilation from baseline in response to iontophoretic delivery of acetylcholine (ACh) in control and diabetic mice treated or not treated with recombinant human erythropoietin (rhEPO), n=8 in each group. (b) Pressure-induced vasodilation. Maximal percentage of vasodilation from baseline during local pressure application in control and diabetic mice treated or not treated with rhEPO, n=10 in each group. *P<0.05, **P<0.01, ***P<0.001 versus respective control mice; ††P<0.01 versus diabetic mice. LDF, laser Doppler flowmetry. Journal of Investigative Dermatology , DOI: ( /jid ) Copyright © 2011 The Society for Investigative Dermatology, Inc Terms and Conditions
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Figure 3 Effect of erythropoietin (EPO) on cutaneous macroscopic and histological findings following 3 hours of pressure. Representative photographs of skin compressed areas and central histological skin compressed sections in untreated (a, b) and in recombinant human erythropoietin (rhEPO)-treated diabetic (c, d) at days 1–3. Histological section: hematoxylin and eosin staining; original magnification × 100; bar=100 μm. (e) Time course of macroscopic stage 2 ulcer areas: control, n=13; diabetic mice, n=12; rhEPO-treated control, n=13; rhEPO-treated diabetic mice, n=10. ***P<0.001 versus respective control mice; †††P<0.001 versus diabetic mice. (f) Central histological pressure ulcer score in control and diabetic mice treated or not treated with rhEPO. ***P<0.001 versus respective control mice; †††P<0.001 versus diabetic mice; n=6 in each group. Journal of Investigative Dermatology , DOI: ( /jid ) Copyright © 2011 The Society for Investigative Dermatology, Inc Terms and Conditions
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