Wound healing in diabetic patients is slower than in healthy individuals. Erythropoietin (EPO) has non-hemopoietic targets in the skin, and systemically administered EPO promotes wound healing in experimental animals. This study investigated the effect of topical EPO treatment on defective wound repair in the skin of diabetic rats. Full-thickness excisional skin wounds were made in 38 rats, of which 30 had diabetes. The wounds were then treated topically with a cream that contained either vehicle, 600 IU ml(-1) EPO (low dose), or 3,000 IU ml(-1) (high dose) EPO. We assessed the rate of wound closure during the 12-day treatment period, and microvascular density (MVD), vascular endothelial growth factor (VEGF), and hydroxyproline (HP) contents, and the extent of apoptosis in wound tissues at the end of the 12-day treatment period. Topical EPO treatment significantly reduced the time to final wound closure. This increased rate of closure of the two EPO-treated wounds in diabetic rats was associated with increased MVD, VEGF, and HP contents, and a reduced extent of apoptosis. In light of our finding that topical EPO treatment promotes skin wound repair in diabetic rats, we propose that topical EPO treatment is a therapeutically beneficial method of treating chronic diabetic wounds.

The Sirius Scheimpflug system has a very high repeatability and intrasessional reproducibility when measuring the ACD, ACA, anterior curvature parameters, and the thinnest corneal location. Thus, it can be used with confidence in clinical practice.

Abstract-Orthostatic stress causes significant plasma shift and raises transmural pressure in lower extremities, resulting in an increase in endothelial activation and plasma proteins concentrations, possibly including coagulation factors. This may lead to activation of the coagulation system during standing. To test this hypothesis, we recruited 18 healthy volunteers (9 females and 9 males; mean age: 25Ϯ1.2 years; body mass index: 21.7Ϯ0.5 kg/m 2 ). Hemodynamics, plasma shift (extrapolated from sequential hematocrit concentration), plasma proteins, and coagulation tests, including procoagulants; fibrinogen, factor V, and factor VIII activity; prothrombin fragments 1 and 2; and endothelial activation-related factors (tissue factor and von Willebrand factor), as well as protein C global pathway, were determined at rest supine and at 15 minutes, 30 minutes, and 60 minutes of still standing. Thirty minutes of standing caused a decrease in plasma volume by 12.0Ϯ0.5% and an increase in plasma protein by 13.0Ϯ0.7%. Fibrinogen, factor V, and factor VIII activity rose by 12.0Ϯ1.2%, 13.0Ϯ1.0%, and 40.0Ϯ6.0% (PϽ0.002 for all), respectively. Prothrombin fragments 1 and 2 were elevated by 150.0Ϯ30.0%. Tissue factor and von Willebrand factor increased by 30.0Ϯ9.0% and 17.4Ϯ51.0% (PϽ0.02 for both), respectively. However, protein C assay results decreased from 0.95Ϯ0.20 to 0.83Ϯ0.16 (PϽ0.001). We hereby introduce a novel physiological mechanism, "orthostatic procoagulation," that should be considered during coagulation tests. Furthermore, it could be extrapolated to the pathophysiology of stasis and venous thromboembolism.