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  • 1
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Tissue repair and wound healing are complex processes that involve inflammation, granulation, and remodeling of the tissue. In this study, we evaluated the in vivo effects of curcumin (difeurloylmethane), a natural product obtained from the rhizomes of Curcuma longa on wound healing in rats and guinea pigs. We observed faster wound closure of punch wounds in curcumin-treated animals in comparison with untreated controls. Biopsies of the wound showed reepithelialization of the epidermis and increased migration of various cells including myofibroblasts, fibroblasts, and macrophages in the wound bed. Multiple areas within the dermis showed extensive neovascularization, and Masson's Trichrome staining showed greater collagen deposition in curcumin-treated wounds. Immunohistochemical localization of transforming growth factor-β1 showed an increase in curcumin-treated wounds as compared with untreated wounds. In situ hybridization and polymerase chain reaction analysis also showed an increase in the mRNA transcripts of transforming growth factor-β1 and fibronectin in curcumin-treated wounds. Because transforming growth factor-β1 is known to enhance wound healing, it may be possible that transforming growth factor-β1 plays an important role in the enhancement of wound healing by curcumin.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Blackwell Publishing Ltd/Inc.
    Wound repair and regeneration 13 (2005), S. 0 
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Wound healing is a complicated biological process that involves interactions of multiple cell types, various growth factors, their mediators and the extracellular matrix proteins. In this study, we have studied the differential regulation of angiogenic genes during wound healing in transgenic diabetic mice and non-diabetic mice. One 8 mm full thickness cutaneous wound under aseptic conditions was created on either side of the midline. Wound tissues were studied at 4, 7, and 11 days postwounding and healing was assessed by histology. The pathway specific gene expression profile of wound tissue in transgenic diabetic mice was compared with the normal mice. Profiling of these genes showed differential regulation of many angiogenic promoters, inhibitors, growth factors and cytokines. Furthermore, in our study hypoxia inducible factor (HIF-1a), osteopontin (OPN) and osteonectin are induced early at day 4, in both the diabetic and nondiabetic wound. The expression was downregulated by 11-day postwounding in the nondiabetic wound, whereas diabetic wounds showed constitutively high expression of these genes. The expression patterns of these genes were concomitant with the extent of healing as assessed by histology at different time point postwounding. These results suggest wound healing is a complex process that involves cascade of interaction of various factors. Although a single gene may not be solely responsible for any impairment in healing; however, an in-depth study of these genes and precise balance between the inducers and inhibitors of angiogenesis may provide an answer to the delayed healing in diabetic conditions.(This work was supported by a grant (5 R21 AT000517-02) from the NCCAM, National Institute of Health, Bethesda, MD.)
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Tissue repair and wound healing are complex processes that involve inflammation, granulation and tissue remodeling. Interactions of different cells, extracellular matrix proteins and their receptors are involved in wound healing, and are mediated by cytokines and growth factors. Previous studies from our laboratory have shown that curcumin (diferuloylmethane), a natural product obtained from the rhizomes of Curcuma longa, enhanced cutaneous wound healing in rats and guinea pigs. In this study, we have evaluated the efficacy of curcumin treatment by oral and topical applications on impaired wound healing in diabetic rats and genetically diabetic mice using a full thickness cutaneous punch wound model. Wounds of animals treated with curcumin showed earlier re-epithelialization, improved neovascularization, increased migration of various cells including dermal myofibroblasts, fibroblasts, and macrophages into the wound bed, and a higher collagen content. Immunohistochemical localization showed an increase in transforming growth factor-β1 in curcumin-treated wounds compared to controls. Enhanced transforming growth factor-β1 mRNA expression in treated wounds was confirmed by in situ hybridization, and laser scan cytometry. A delay in the apoptosis patterns was seen in diabetic wounds compared to curcumin treated wounds as shown by terminal deoxynucleotidyl transferase–mediated deoxyuridyl triphosphate nick end labeling analysis. Curcumin was effective both orally and topically. These results show that curcumin enhanced wound repair in diabetic impaired healing, and could be developed as a pharmacological agent in such clinical settings.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK; Malden, USA : Blackwell Publishing Ltd/Inc.
    Wound repair and regeneration 13 (2005), S. 0 
    ISSN: 1524-475X
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Tissue repair and wound healing are complex processes that involve inflammation, granulation, and tissue remodeling. Angiogenesis plays a central role in wound healing. Previously, we have shown that picroliv, a natural product obtained from the roots of Picrorhiza kurrooa upregulates the expression of vascular endothelial growth factor (VEGF) in human umbilical vein endothelial cells and insulin like growth factor (IGF) in rats during hypoxia (Cellular and Molecular Life Sciences 1999; 56: 348–55). In the present study, we have investigated the effect of Picroliv in an ex vivo rat aorta ring model of angiogenesis. Picroliv enhanced the sprouting and migration of endothelial cells. In this study, we have investigated the effect of picroliv in both unimpaired and dexamethasone (DX)-induced impaired cutaneous healing in a full thickness punch wound model in rats. The animals in the impaired healing group having been pretreated with DX. We studied the tissues by histology and morphometry. The data showed picroliv treatment resulted in improved reepithelialization, neovascularization, and migration of various cells such as endothelial, dermal myofibroblasts, and fibroblasts into the wound bed. Immunohistochemical localization showed an increased VEGF and alpha smooth muscle actin staining consistent with increased number of micro vessels in granulation tissue. These findings suggest that picroliv accelerated wound repair and thus could be developed as a therapeutic angiogenic agent for the wound healing.(This work was supported by a grant (5 R21 AT000517-02) from the NCCAM, National Institute of Health, Bethesda, MD.)
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1573-4919
    Keywords: hypoxia ; reoxygenation ; picroliv ; antioxidant ; tyrosine phosphorylation ; protein kinase C
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Abstract Cellular adaptation to hypoxia involves regulation of specific genes such as vascular endothelial growth factor (VEGF), erythropoietin (EPO) and hypoxia inducible factor (HIF)-1. In this study, we have evaluated the protective effect of picroliv (a purified iridoid glycoside fraction from roots of Picrorhiza kurrooa with hepatoprotective, anti-inflammatory and antioxidant properties) against hypoxic injury by examining lactate dehydrogenase (LDH) release in Hep 3B and Glioma cells. The expression of hypoxia regulated genes, VEGF and HIF-1 was studied in human umbilical vein endothelial cells (HUVEC), Hep 3B and Glioma cells. Picroliv reduced the cellular damage caused by hypoxia as revealed by a significant reduction in LDH release compared to untreated control. The expression of VEGF and HIF-1 subunits (HIF-1α and HIF-1β) was enhanced by treatment with picroliv during normoxia and hypoxia in HUVEC and Hep 3B cells and on reoxygenation the expression of these genes was significantly reduced as revealed by mRNA analysis using RT-PCR. Simultaneous treatment with picroliv during hypoxia inhibited VEGF and HIF-1 expression in Glioma cells whereas the expression was not reduced by picroliv treatment during reoxygenation as evidenced by both RT-PCR and Northern hybridization. VEGF expression as revealed by immunofluorescence studies correlates well with the regulations observed in the MRNA expression. We have also examined the kinase activity of tyrosine phosphorylated proteins and protein kinase C (PKC) in Glioma cells treated with picroliv during hypoxia/reoxygenation. A selective inhibition of protein tyrosine kinase activity leading to tyrosine dephosphorylation of several proteins including 80 kd protein, and a reduction in PKC was seen in cells treated with picroliv and hypoxia. These findings suggest that picroliv may act as a protective agent against hypoxia/reoxygenation induced injuries, and the underlying mechanism may involve a novel signal transduction pathway.
    Type of Medium: Electronic Resource
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