Differential Modulation of Angiogenesis by Erythropoiesis-Stimulating Agents in a Mouse Model of Ischaemic Retinopathy

BACKGROUND: Erythropoiesis stimulating agents (ESAs) are widely used to treat anaemia but concerns exist about their potential to promote pathological angiogenesis in some clinical scenarios. In the current study we have assessed the angiogenic potential of three ESAs; epoetin delta, darbepoetin alfa and epoetin beta using in vitro and in vivo models. METHODOLOGY/PRINCIPAL FINDINGS: The epoetins induced angiogenesis in human microvascular endothelial cells at high doses, although darbepoetin alfa was pro-angiogenic at low-doses (1-20 IU/ml). ESA-induced angiogenesis was VEGF-mediated. In a mouse model of ischaemia-induced retinopathy, all ESAs induced generation of reticulocytes but only epoetin beta exacerbated pathological (pre-retinal) neovascularisation in comparison to controls (p<0.05). Only epoetin delta induced a significant revascularisation response which enhanced normality of the vasculature (p<0.05). This was associated with mobilisation of haematopoietic stem cells and their localisation to the retinal vasculature. Darbepoetin alfa also increased the number of active microglia in the ischaemic retina relative to other ESAs (p<0.05). Darbepoetin alfa induced retinal TNFalpha and VEGF mRNA expression which were up to 4 fold higher than with epoetin delta (p<0.001). CONCLUSIONS: This study has implications for treatment of patients as there are clear differences in the angiogenic potential of the different ESAs

NMR analysis of the chain microstructure of biodegradable terpolymers with shape memory properties

Terpolymers of lactide, glycolide and trimethylene carbonate initiated on zirconium acetylacetonate (IV) exhibit shape-memory behaviors in the range of body temperature when appropriate monomer composition and characterizing conditions are applied. In this paper, the procedure of characterizing these terpolymers by means of nuclear magnetic resonance spectroscopy is presented. The 1H and 13C NMR spectra allow to characterize the chain microstructure of these polyester-carbonates in spite of overlapping resonance signals due to the possibility of forming different co-monomeric sequences. Detailed assignment was given for spectral lines in proton and carbon spectra recorded in polar and non-polar deuterated solvents. For quantitative analysis, equations for calculations of average block lengths, long and mixed glycolidyl, lactidyl and carbonate blocks as well as formulas allowing to investigate intramolecular transestrification processes were elaborated