1. |
- Scherfer, Christoph, et al.
(författare)
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The Toll immune-regulated Drosophila protein Fondue is involved in hemolymph clotting and puparium formation
- 2006
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Ingår i: Developmental Biology. - : Elsevier BV. - 0012-1606 .- 1095-564X. ; 295, s. 156-163
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Tidskriftsartikel (refereegranskat)abstract
- Clotting is critical in limiting hemolymph loss and initiating wound healing in insects as in vertebrates. It is also an important immune defense, quickly forming a secondary barrier to infection, immobilizing bacteria and thereby promoting their killing. However, hemolymph clotting is one of the least understood immune responses in insects. Here, we characterize fondue (fon; CG15825), an immune-responsive gene of Drosophila melanogaster that encodes an abundant hemolymph protein containing multiple repeat blocks. After knockdown of fon by RNAi, bead aggregation activity of larval hemolymph is strongly reduced, and wound closure is affected. Jon is thus the second Drosophila gene after hemolectin (hml), for which a knockdown causes a clotting phenotype. In contrast to hml-RNAi larvae, clot fibers are still observed in samples from fon-RNAi larvae. However, clot fibers from fon-RNAi larvae are more ductile and longer than in wt hemolymph samples, indicating that Fondue might be involved in cross-linking of fiber proteins. In addition, fon-RNAi larvae exhibit melanotic tumors and constitutive expression of the antifungal peptide gene Drosomycin (Drs), while fon-RNAi pupae display an aberrant pupal phenotype. Altogether, our studies indicate that Fondue is a major hemolymph protein required for efficient clotting in Drosophila.
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2. |
- Velander, Patrik, et al.
(författare)
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Cell Suspensions of Autologous Keratinocytes or Autologous Fibroblasts Accelerate the Healing of Full Thickness Skin Wounds in a Diabetic Porcine Wound Healing Model.
- 2009
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Ingår i: The Journal of surgical research. - : Elsevier BV. - 1095-8673 .- 0022-4804. ; 157, s. 14-20
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Tidskriftsartikel (refereegranskat)abstract
- Autologous dermal fibroblasts may be useful in the treatment of diabetic skin wounds. We hypothesized that cultured fibroblasts or cultured keratinocytes would not only survive in a hyperglycemic wound environment but also enhance the rate of re-epithelialization. We previously developed a new porcine model of delayed cutaneous wound healing in the diabetic pig. Full thickness wounds were created on the dorsum and dressed with polyurethane chambers to keep the wounds wet and to allow for wound fluid monitoring. Suspensions of either autologous fibroblasts or autologous keratinocytes were injected into full thickness wounds and compared with wounds treated in a wet environment in normal saline. Serum glucose and wound fluid glucose concentrations were monitored daily. Wound contraction was monitored and biopsies taken on day 12. Transplantation of suspensions of autologous fibroblasts or autologous keratinocytes enhanced re-epithelialization of cutaneous full thickness wounds. Wounds treated with autologous fibroblasts showed a re-epithelialization rate of 86.75% and wounds treated with autologous keratinocytes showed a re-epithelialization rate of 91.3%. This is compared with a re-epithelialization rate of 56.8% seen in the normal saline treated wounds. While previous studies have shown fibroblasts suspension to have little effect in the treatment of full thickness wounds in nondiabetic wounds, this study shows a clear beneficial effect in the use of fibroblast or keratinocyte suspensions for the cutaneous healing of diabetic wounds in pigs.
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3. |
- Velander, Patrik, et al.
(författare)
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Impaired wound healing in an acute diabetic pig model and the effects of local hyperglycemia.
- 2008
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Ingår i: Wound Repair and Regeneration. - 1524-475X. ; 16:2, s. 288-293
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Tidskriftsartikel (refereegranskat)abstract
- Diabetic wounds result in significant morbidity, prolonged hospitalization, and enormous health-care expenses. Pigs have been shown to have wound healing resembling that in humans. The aim of this study was to develop a large-animal model for diabetic wound healing. Diabetes was induced by streptozotocin injection in Yorkshire pigs. Full-thickness wounds were created and dressed with a sealed chamber. Nondiabetic pigs with or without high glucose wound fluid concentration served as controls. Glucose concentration in serum and wound fluid was measured and collected. Wound contraction was monitored, and biopsies were obtained for measurement of reepithelialization. Wound fluid was analyzed for insulin-like growth factor-1 (IGF-1), platelet-derived growth factor, and transforming growth factor. Glucose concentration in wound fluid initially followed serum levels and then decreased to undetectable on day 9. Reepithelialization was significantly delayed in diabetic pigs. In nondiabetic pigs, wounds treated in a local hyperglycemic environment, and thus excluding the effects of systemic hyperglycemia, showed no difference in wound closure compared with controls. This suggests that delayed wound healing in diabetes is not induced by local high-glucose concentration itself. Analysis of growth factor expression showed a marked reduction in IGF-1 in the diabetic wounds. Diabetic pigs have impaired healing that is accompanied by a reduction of IGF-1 in the healing wound and is not due to the local hyperglycemia condition itself.
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