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Sample records for coordinately regulate wound

  1. Endocytosis-dependent coordination of multiple actin regulators is required for wound healing

    Science.gov (United States)

    Matsubayashi, Yutaka; Coulson-Gilmer, Camilla

    2015-01-01

    The ability to heal wounds efficiently is essential for life. After wounding of an epithelium, the cells bordering the wound form dynamic actin protrusions and/or a contractile actomyosin cable, and these actin structures drive wound closure. Despite their importance in wound healing, the molecular mechanisms that regulate the assembly of these actin structures at wound edges are not well understood. In this paper, using Drosophila melanogaster embryos, we demonstrate that Diaphanous, SCAR, and WASp play distinct but overlapping roles in regulating actin assembly during wound healing. Moreover, we show that endocytosis is essential for wound edge actin assembly and wound closure. We identify adherens junctions (AJs) as a key target of endocytosis during wound healing and propose that endocytic remodeling of AJs is required to form “signaling centers” along the wound edge that control actin assembly. We conclude that coordination of actin assembly, AJ remodeling, and membrane traffic is required for the construction of a motile leading edge during wound healing. PMID:26216900

  2. Modeling closure of circular wounds through coordinated collective motion.

    Science.gov (United States)

    Li, David S; Zimmermann, Juliane; Levine, Herbert

    2016-02-12

    Wound healing enables tissues to restore their original states, and is achieved through collective cell migration into the wound space, contraction of the wound edge via an actomyosin filament 'purse-string,' as well as cell division. Recently, experimental techniques have been developed to create wounds with various regular morphologies in epithelial monolayers, and these experiments of circular closed-contour wounds support coordinated lamellipodial cell crawling as the predominant driver of gap closure. Through utilizing a particle-based mechanical tissue simulation, exhibiting long-range coordination of cell motility, we computationally model these closed-contour experiments with a high level of agreement between experimentally observed and simulated wound closure dynamics and tissue velocity profiles. We also determine the sensitivity of wound closure time in the model to changes in cell motility force and division rate. Our simulation results confirm that circular wounds can close due to collective cell migration without the necessity for a purse-string mechanism or for cell division, and show that the alignment mechanism of cellular motility force with velocity, leading to collective motion in the model, may speed up wound closure.

  3. The alpha3 laminin subunit, alpha6beta4 and alpha3beta1 integrin coordinately regulate wound healing in cultured epithelial cells and in the skin

    DEFF Research Database (Denmark)

    Goldfinger, L E; Hopkinson, S B; deHart, G W

    1999-01-01

    Previously, we demonstrated that proteolytic processing within the globular domain of the alpha3 subunit of laminin-5 (LN5) converts LN5 from a cell motility-inducing factor to a protein complex that can trigger the formation of hemidesmosomes, certain cell-matrix attachment sites found in epithe......-inhibiting antibodies, we provide evidence that LN5 and its two integrin receptors (alpha6beta4 and alpha3beta1) appear necessary for wound healing to occur in MCF-10A cell culture wounds. We propose a model for healing of wounded epithelial tissues based on these results....... in epithelial cells. We have prepared a monoclonal antibody (12C4) whose epitope is located toward the carboxy terminus of the globular domain of the alpha3 laminin subunit. This epitope is lost from the alpha3 subunit as a consequence of proteolytic processing. Antibody 12C4 stains throughout the matrix...... the wound site. A similar phenomenon is observed in human skin wounds, since we also detect expression of the unprocessed alpha3 laminin subunit at the leading tip of the sheet of epidermal cells that epithelializes skin wounds in vivo. In addition, using alpha3 laminin subunit and integrin function...

  4. Metalloproteinases and Their Inhibitors: Regulators of Wound Healing

    Science.gov (United States)

    Gill, Sean E.; Parks, William C.

    2008-01-01

    Wound healing is a dynamic process that involves a coordinated response of many cell types representing distinct tissue compartments and is fundamentally similar among tissue types. Among the many gene products that are essential for restoration normal tissue architecture, several members of the matrix metalloproteinase (MMP) function as positive and, at times, negative regulators of repair processes. MMPs were initially thought to only function in the resolution phase of wound healing, particularly during scar resorption; however, recent evidence suggests that they also influence other wound-healing responses, such as inflammation and re-epithelialization. In this review, we discuss what is currently known about the function of MMPs in wound healing and will provide suggestions for future research directions. PMID:18083622

  5. Inhibition of IRF8 Negatively Regulates Macrophage Function and Impairs Cutaneous Wound Healing.

    Science.gov (United States)

    Guo, Yuanyuan; Yang, Zhiyin; Wu, Shan; Xu, Peng; Peng, Yinbo; Yao, Min

    2017-02-01

    The inflammatory response is essential for normal cutaneous wound healing. Macrophages, as critical inflammatory cells, coordinate inflammation and angiogenesis phases during wound healing. It has been reported that the transcription factor interferon regulatory factor 8 (IRF8), a member of the IRF family, plays a critical role in the development and function of macrophages and is associated with inflammation. However, the role of IRF8 in cutaneous wound healing and its underlying mechanism remain elusive. Through immunohistochemical (IHC) staining, we showed that IRF8 is involved in the wound repair process in mice and patients. Furthermore, we ascertain that the repression of IRF8 by small interfering RNA (siRNA) leads to delayed wound healing. To explore the mechanism by which IRF8 impacts wound healing, we observed its effect on macrophage-related mediators by IHC or real-time PCR. The results demonstrated that the inhibition of IRF8 decreases the mRNA expression of inflammatory mediators associated with M1 macrophage (il-1b, il-6, inos, and tnf-a) but no impact on M2 macrophage-related mediators (arg-1, mrc-1, and il-10) and the number of macrophages in the wounds. Furthermore, the inhibition of IRF8 induced apoptosis in the wounds. In summary, this study demonstrates that the down-regulation of IRF8 in the wound leads to impaired wound healing possibly through the regulation of macrophage function and apoptosis in skin wound.

  6. Improved wound management by regulated negative pressure-assisted wound therapy and regulated, oxygen- enriched negative pressure-assisted wound therapy through basic science research and clinical assessment

    OpenAIRE

    Moris Topaz

    2012-01-01

    Regulated negative pressure-assisted wound therapy (RNPT) should be regarded as a state-of-the-art technology in wound treatment and the most important physical, nonpharmaceutical, platform technology developed and applied for wound healing in the last two decades. RNPT systems maintain the treated wound's environment as a semi-closed, semi-isolated system applying external physical stimulations to the wound, leading to biological and biochemical effects, with the potential to substantially i...

  7. Notch Regulates Macrophage-Mediated Inflammation in Diabetic Wound Healing

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    Andrew S. Kimball

    2017-06-01

    Full Text Available Macrophages are essential immune cells necessary for regulated inflammation during wound healing. Recent studies have identified that Notch plays a role in macrophage-mediated inflammation. Thus, we investigated the role of Notch signaling on wound macrophage phenotype and function during normal and diabetic wound healing. We found that Notch receptor and ligand expression are dynamic in wound macrophages during normal healing. Mice with a myeloid-specific Notch signaling defect (DNMAMLfloxedLyz2Cre+ demonstrated delayed early healing (days 1–3 and wound macrophages had decreased inflammatory gene expression. In our physiologic murine model of type 2 diabetes (T2D, Notch receptor expression was significantly increased in wound macrophages on day 6, following the initial inflammatory phase of wound healing, corresponding to increased inflammatory cytokine expression. This increase in Notch1 and Notch2 was also observed in human monocytes from patients with T2D. Further, in prediabetic mice with a genetic Notch signaling defect (DNMAMLfloxedLyz2Cre+ on a high-fat diet, improved wound healing was seen at late time points (days 6–7. These findings suggest that Notch is critical for the early inflammatory phase of wound healing and directs production of macrophage-dependent inflammatory mediators. These results identify that canonical Notch signaling is important in directing macrophage function in wound repair and define a translational target for the treatment of non-healing diabetic wounds.

  8. Improved wound management by regulated negative pressure-assisted wound therapy and regulated, oxygen- enriched negative pressure-assisted wound therapy through basic science research and clinical assessment.

    Science.gov (United States)

    Topaz, Moris

    2012-05-01

    Regulated negative pressure-assisted wound therapy (RNPT) should be regarded as a state-of-the-art technology in wound treatment and the most important physical, nonpharmaceutical, platform technology developed and applied for wound healing in the last two decades. RNPT systems maintain the treated wound's environment as a semi-closed, semi-isolated system applying external physical stimulations to the wound, leading to biological and biochemical effects, with the potential to substantially influence wound-host interactions, and when properly applied may enhance wound healing. RNPT is a simple, safe, and affordable tool that can be utilized in a wide range of acute and chronic conditions, with reduced need for complicated surgical procedures, and antibiotic treatment. This technology has been shown to be effective and safe, saving limbs and lives on a global scale. Regulated, oxygen-enriched negative pressure-assisted wound therapy (RO-NPT) is an innovative technology, whereby supplemental oxygen is concurrently administered with RNPT for their synergistic effect on treatment and prophylaxis of anaerobic wound infection and promotion of wound healing. Understanding the basic science, modes of operation and the associated risks of these technologies through their fundamental clinical mechanisms is the main objective of this review.

  9. Innate defense regulator peptide 1018 in wound healing and wound infection.

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    Lars Steinstraesser

    Full Text Available Innate defense regulators (IDRs are synthetic immunomodulatory versions of natural host defense peptides (HDP. IDRs mediate protection against bacterial challenge in the absence of direct antimicrobial activity, representing a novel approach to anti-infective and anti-inflammatory therapy. Previously, we reported that IDR-1018 selectively induced chemokine responses and suppressed pro-inflammatory responses. As there has been an increasing appreciation for the ability of HDPs to modulate complex immune processes, including wound healing, we characterized the wound healing activities of IDR-1018 in vitro. Further, we investigated the efficacy of IDR-1018 in diabetic and non-diabetic wound healing models. In all experiments, IDR-1018 was compared to the human HDP LL-37 and HDP-derived wound healing peptide HB-107. IDR-1018 was significantly less cytotoxic in vitro as compared to either LL-37 or HB-107. Furthermore, administration of IDR-1018 resulted in a dose-dependent increase in fibroblast cellular respiration. In vivo, IDR-1018 demonstrated significantly accelerated wound healing in S. aureus infected porcine and non-diabetic but not in diabetic murine wounds. However, no significant differences in bacterial colonization were observed. Our investigation demonstrates that in addition to previously reported immunomodulatory activities IDR-1018 promotes wound healing independent of direct antibacterial activity. Interestingly, these effects were not observed in diabetic wounds. It is anticipated that the wound healing activities of IDR-1018 can be attributed to modulation of host immune pathways that are suppressed in diabetic wounds and provide further evidence of the multiple immunomodulatory activities of IDR-1018.

  10. Improved wound management by regulated negative pressure-assisted wound therapy and regulated, oxygen- enriched negative pressure-assisted wound therapy through basic science research and clinical assessment

    Directory of Open Access Journals (Sweden)

    Moris Topaz

    2012-01-01

    Full Text Available Regulated negative pressure-assisted wound therapy (RNPT should be regarded as a state-of-the-art technology in wound treatment and the most important physical, nonpharmaceutical, platform technology developed and applied for wound healing in the last two decades. RNPT systems maintain the treated wound′s environment as a semi-closed, semi-isolated system applying external physical stimulations to the wound, leading to biological and biochemical effects, with the potential to substantially influence wound-host interactions, and when properly applied may enhance wound healing. RNPT is a simple, safe, and affordable tool that can be utilized in a wide range of acute and chronic conditions, with reduced need for complicated surgical procedures, and antibiotic treatment. This technology has been shown to be effective and safe, saving limbs and lives on a global scale. Regulated, oxygen-enriched negative pressure-assisted wound therapy (RO-NPT is an innovative technology, whereby supplemental oxygen is concurrently administered with RNPT for their synergistic effect on treatment and prophylaxis of anaerobic wound infection and promotion of wound healing. Understanding the basic science, modes of operation and the associated risks of these technologies through their fundamental clinical mechanisms is the main objective of this review.

  11. Wounding coordinately induces cell wall protein, cell cycle and pectin methyl esterase genes involved in tuber closing layer and wound periderm development

    Science.gov (United States)

    Potato (Solanum tuberosum L.) is the world’s fourth largest food crop and large financial losses are incurred each year from wound and bruise related injuries. However, little is known about the coordinate induction of genes that may be associated with or mark major wound-healing events. In this s...

  12. Coordinated waves of actomyosin flow and apical cell constriction immediately after wounding.

    Science.gov (United States)

    Antunes, Marco; Pereira, Telmo; Cordeiro, João V; Almeida, Luis; Jacinto, Antonio

    2013-07-22

    Epithelial wound healing relies on tissue movements and cell shape changes. Our work shows that, immediately after wounding, there was a dramatic cytoskeleton remodeling consisting of a pulse of actomyosin filaments that assembled in cells around the wound edge and flowed from cell to cell toward the margin of the wound. We show that this actomyosin flow was regulated by Diaphanous and ROCK and that it elicited a wave of apical cell constriction that culminated in the formation of the leading edge actomyosin cable, a structure that is essential for wound closure. Calcium signaling played an important role in this process, as its intracellular concentration increased dramatically immediately after wounding, and down-regulation of transient receptor potential channel M, a stress-activated calcium channel, also impaired the actomyosin flow. Lowering the activity of Gelsolin, a known calcium-activated actin filament-severing protein, also impaired the wound response, indicating that cleaving the existing actin filament network is an important part of the cytoskeleton remodeling process.

  13. Innate Defense Regulator Peptide 1018 in Wound Healing and Wound Infection

    DEFF Research Database (Denmark)

    Steinstraesser, Lars; Hirsch, Tobias; Schulte, Matthias

    2012-01-01

    -37 or HB-107. Furthermore, administration of IDR-1018 resulted in a dose-dependent increase in fibroblast cellular respiration. In vivo, IDR-1018 demonstrated significantly accelerated wound healing in S. aureus infected porcine and non-diabetic but not in diabetic murine wounds. However...

  14. Differential Regulation of Wound-Induced 1-Aminocyclopropane-1 ...

    African Journals Online (AJOL)

    Northern blot nalysis was applied to total RNNA using labeled probes prepared by a multiprimer DNA labeling system and α-[32P]dCTP with a Hindi> III fragment from pCMW33, a wound inducible ACC synthase gene as a template. CO2 suppressed wound-induced ethylene production, ACC synthase and ACC oxidase ...

  15. Wound induced tanscriptional regulation of benzylisoquinoline pathway and characterization of wound inducible PsWRKY transcription factor from Papaver somniferum.

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    Sonal Mishra

    Full Text Available Wounding is required to be made in the walls of the green seed pod of Opium poppy prior exudation of latex. To withstand this kind of trauma plants regulate expression of some metabolites through an induced transcript level. 167 unique wound-inducible ESTs were identified by a repetitive round of cDNA subtraction after 5 hours of wounding in Papaver somniferum seedlings. Further repetitive reverse northern analysis of these ESTs revealed 80 transcripts showing more than two fold induction, validated through semi-quantitative RT-PCR & real time expression analysis. One of the major classified categories among identified ESTs belonged to benzylisoquinoline transcripts. Tissue specific metabolite analysis of benzylisoquinoline alkaloids (BIAs in response to wounding revealed increased accumulation of narcotine and papaverine. Promoter analysis of seven transcripts of BIAs pathway showed the presence of W-box cis-element with the consensus sequence of TGAC, which is the proposed binding site for WRKY type transcription factors. One of the Wound inducible 'WRKY' EST isolated from our subtracted library was made full-length and named as 'PsWRKY'. Bacterially expressed PsWRKY interacted with the W-box element having consensus sequence TTGACT/C present in the promoter region of BIAs biosynthetic pathway genes. PsWRKY further activated the TYDC promoter in yeast and transiently in tobacco BY2 cells. Preferential expression of PsWRKY in straw and capsule and its interaction with consensus W-box element present in BIAs pathway gene transcripts suggest its possible involvement in the wound induced regulation of BIAs pathway.

  16. Macrophages and fibroblasts : key regulators in wound healing, fibrosis and the foreign body reaction

    NARCIS (Netherlands)

    Ploeger, Diana

    2017-01-01

    Macrophages and fibroblasts are key regulators in wound healing, fibrosis and foreign body reaction (FBR). After injury macrophages migrate through the extracellular matrix (ECM) towards the wounded area, and adopt a M1 or M2 phenotype. M1 macrophages are associated with tissue injury and

  17. Coordinate expression of AOS genes and JA accumulation: JA is not required for initiation of closing layer in wound healing tubers

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    Wounding induces a series of coordinated physiological responses essential for protection and healing of the damaged tissue. Wound-induced formation of jasmonic acid (JA) is important in defense responses in leaves, but comparatively little is known about the induction of JA biosynthesis and its ro...

  18. ERK and phosphoinositide 3-kinase temporally coordinate different modes of actin-based motility during embryonic wound healing

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    Li, Jingjing; Zhang, Siwei; Soto, Ximena; Woolner, Sarah; Amaya, Enrique

    2013-01-01

    Summary Embryonic wound healing provides a perfect example of efficient recovery of tissue integrity and homeostasis, which is vital for survival. Tissue movement in embryonic wound healing requires two functionally distinct actin structures: a contractile actomyosin cable and actin protrusions at the leading edge. Here, we report that the discrete formation and function of these two structures is achieved by the temporal segregation of two intracellular upstream signals and distinct downstream targets. The sequential activation of ERK and phosphoinositide 3-kinase (PI3K) signalling divides Xenopus embryonic wound healing into two phases. In the first phase, activated ERK suppresses PI3K activity, and is responsible for the activation of Rho and myosin-2, which drives actomyosin cable formation and constriction. The second phase is dominated by restored PI3K signalling, which enhances Rac and Cdc42 activity, leading to the formation of actin protrusions that drive migration and zippering. These findings reveal a new mechanism for coordinating different modes of actin-based motility in a complex tissue setting, namely embryonic wound healing. PMID:23986484

  19. Systemic Effect of Angipars on Regulation of Wound Healing is ...

    African Journals Online (AJOL)

    Purpose: To measure CXCL10 as angiostatic, and CXCL1, CXCL12 as angiogenic chemokines in the tissues of wounds of diabetics following treatment with insulin, angipars (a herbal Iranian drug) and a combination of angipars and insulin. Methods: Forty eight male Wistar rats weighing 200 - 250 g were used.

  20. Emdogain regulation of cellular differentiation in wounded rat periodontium.

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    Chano, Laura; Tenenbaum, Howard C; Lekic, P Charles; Sodek, Jaro; McCulloch, Christopher A

    2003-04-01

    Emdogain is an enamel matrix derivative that may promote periodontal regeneration by recapitulating critical events in tooth morphogenesis. We hypothesized that Emdogain enhances periodontal regeneration by promoting the differentiation of cells required for the synthesis of periodontal ligament, bone and cementum. Cell differentiation was examined in rat periodontal window wounds in which there is no microbial biofilm or epithelial downgrowth, thereby simplifying the model system. Defects were filled with vehicle control or Emdogain (3 mg/ml or 30 mg/ml). Rats were sacrificed at 7, 14 and 21 d after wounding. Specimens of periodontium were immunostained for osteopontin, bone sialoprotein, osteocalcin as markers of osteogenic differentiation and for alpha-smooth muscle actin, a myofibroblastic marker. Morphometry and 3H-proline radioautography were used for assessment of tissue homeostasis and matrix production. Rats treated with Emdogain (only at 30 mg/ml) showed widening of the periodontal ligament at 7 d; by 14 and 21 d, periodontal ligament width was restored to normal values for all groups. Emdogain exerted no effect on cementum thickness, bone volume, osteoid deposition rates, or extracellular staining for osteopontin, bone sialoprotein or osteocalcin. Further, the percentage of cells with intracellular staining for osteopontin, osteocalcin or bone sialoprotein was unaffected by Emdogain. Staining for alpha-smooth muscle actin was abundant in the repopulating wound but was also unaffected by Emdogain. In conclusion, Emdogain does not apparently affect the expression of differentiation markers or bone matrix protein synthesis in the repopulation response of wounded rat molar periodontium. Therefore the effect of Emdogain on wound healing in the periodontium may be independent of differentiation in the cell populations examined in this model.

  1. Rapid systemic up-regulation of genes after heat-wounding and electrical stimulation

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    Davies, E.; Vian, A.; Vian, C.; Stankovic, B.

    1997-01-01

    When one leaf of a tomato plant is electrically-stimulated or heat-wounded, proteinase inhibitor genes are rapidly up-regulated in distant leaves. The identity of the systemic wound signal(s) is not yet known, but major candidates include hormones transmitted via the phloem or the xylem, the electrically-stimulated self-propagating electrical signal in the phloem (the action potential, AP), or the heat-wound-induced surge in hydraulic pressure in the xylem evoking a local change in membrane potential in adjacent living cells (the variation potential, VP). In order to discriminate between these signals we have adopted two approaches. The first approach involves applying stimuli that evoke known signals and determining whether these signals have similar effects on the "model" transcripts for proteinase inhibitors (pin) and calmodulin (cal). Here we show that a heat wound almost invariably evokes a VP, while an electrical stimulation occasionally evokes an AP, and both of these signals induce accumulation of transcripts encoding proteinase inhibitors. The second approach involves identifying the array of genes turned on by heat-wounding. To this end, we have constructed a subtractive library for heat-wounded tissue, isolated over 800 putatively up-regulated clones, and shown that all but two of the fifty that we have analyzed by Northern hybridization are, indeed, up-regulated. Here we show the early kinetics of up-regulation of three of these transcripts in the terminal (4th) leaf in response to heat-wounding the 3rd leaf, about 5 cm away. Even though these transcripts show somewhat different time courses of induction, with one peaking at 30 min, another at 15 min, and another at 5 min after flaming of a distant leaf, they all exhibit a similar pattern, i.e., a transient period of transcript accumulation preceding a period of transcript decrease, followed by a second period of transcript accumulation.

  2. RIP2: A novel player in the regulation of keratinocyte proliferation and cutaneous wound repair?

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    Adams, Stephanie; Valchanova, Ralitsa S. [Charite-University Medicine Berlin, Institute of Physiology, Arnimallee 22, D-14195 Berlin (Germany); Munz, Barbara, E-mail: barbara.munz@charite.de [Charite-University Medicine Berlin, Institute of Physiology, Arnimallee 22, D-14195 Berlin (Germany)

    2010-03-10

    We could recently demonstrate an important role of receptor interacting protein 4 (RIP4) in the regulation of keratinocyte differentiation. Now, we analyzed a potential role of the RIP4 homolog RIP2 in keratinocytes. Specifically, we demonstrate here that rip2 expression is induced by scratch-wounding and after the induction of differentiation in these cells. Furthermore, serum growth factors and cytokines can induce rip2, with TNF-{alpha}-dependent induction being dependent on p38 MAPK. In addition, we demonstrate that scratch-induced upregulation of rip2 expression is completely blocked by the steroid dexamethasone. Since we also show that RIP2 is an important player in the regulation of keratinocyte proliferation, these data suggest that inhibition of rip2 upregulation after wounding might contribute to the reduced and delayed wound re-epithelialization phenotype seen in glucocorticoid-treated patients.

  3. Pigment epithelium-derived factor as a multifunctional regulator of wound healing

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    Wietecha, Mateusz S.; Król, Mateusz J.; Michalczyk, Elizabeth R.; Chen, Lin; Gettins, Peter G.

    2015-01-01

    During dermal wound repair, hypoxia-driven proliferation results in dense but highly permeable, disorganized microvascular networks, similar to those in solid tumors. Concurrently, activated dermal fibroblasts generate an angiopermissive, provisional extracellular matrix (ECM). Unlike cancers, wounds naturally resolve via blood vessel regression and ECM maturation, which are essential for reestablishing tissue homeostasis. Mechanisms guiding wound resolution are poorly understood; one candidate regulator is pigment epithelium-derived factor (PEDF), a secreted glycoprotein. PEDF is a potent antiangiogenic in models of pathological angiogenesis and a promising cancer and cardiovascular disease therapeutic, but little is known about its physiological function. To examine the roles of PEDF in physiological wound repair, we used a reproducible model of excisional skin wound healing in BALB/c mice. We show that PEDF is abundant in unwounded and healing skin, is produced primarily by dermal fibroblasts, binds to resident microvascular endothelial cells, and accumulates in dermal ECM and epidermis. PEDF transcript and protein levels were low during the inflammatory and proliferative phases of healing but increased in quantity and colocalization with microvasculature during wound resolution. Local antibody inhibition of endogenous PEDF delayed vessel regression and collagen maturation during the remodeling phase. Treatment of wounds with intradermal injections of exogenous, recombinant PEDF inhibited nascent angiogenesis by repressing endothelial proliferation, promoted vascular integrity and function, and increased collagen maturity. These results demonstrate that PEDF contributes to the resolution of healing wounds by causing regression of immature blood vessels and stimulating maturation of the vascular microenvironment, thus promoting a return to tissue homeostasis after injury. PMID:26163443

  4. Systemic Effect of Angipars on Regulation of Wound Healing is ...

    African Journals Online (AJOL)

    yahoo.com; ... regulation of angiogenesis and inflammation via balancing of chemokines expression. Keywords: Diabetes mellitus, Angipars, Insulin, ... using a glucometer device and animals having a blood glucose level above 300 mg/dl were.

  5. Coordinate regulation of DNA methyltransferase expression during oogenesis

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    Bestor Timothy H

    2007-04-01

    Full Text Available Abstract Background Normal mammalian development requires the action of DNA methyltransferases (DNMTs for the establishment and maintenance of DNA methylation within repeat elements and imprinted genes. Here we report the expression dynamics of Dnmt3a and Dnmt3b, as well as a regulator of DNA methylation, Dnmt3L, in isolated female germ cells. Results Our results indicate that these enzymes are coordinately regulated and that their expression peaks during the stage of postnatal oocyte development when maternal methylation imprints are established. We find that Dnmt3a, Dnmt3b, Dnmt3L and Dnmt1o transcript accumulation is related to oocyte diameter. Furthermore, DNMT3L deficient 15 dpp oocytes have aberrantly methylated Snrpn, Peg3 and Igf2r DMRs, but normal IAP and LINE-1 methylation levels, thereby highlighting a male germ cell specific role for DNMT3L in the establishment of DNA methylation at repeat elements. Finally, real-time RT-PCR analysis indicates that the depletion of either DNMT3L or DNMT1o in growing oocytes results in the increased expression of the de novo methyltransferase Dnmt3b, suggesting a potential compensation mechanism by this enzyme for the loss of one of the other DNA methyltransferases. Conclusion Together these results provide a better understanding of the developmental regulation of Dnmt3a, Dnmt3b and Dnmt3L at the time of de novo methylation during oogenesis and demonstrate that the involvement of DNMT3L in retrotransposon silencing is restricted to the male germ line. This in turn suggests the existence of other factors in the oocyte that direct DNA methylation to transposons.

  6. Foxn1 Transcription Factor Regulates Wound Healing of Skin through Promoting Epithelial-Mesenchymal Transition.

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    Barbara Gawronska-Kozak

    Full Text Available Transcription factors are key molecules that finely tune gene expression in response to injury. We focused on the role of a transcription factor, Foxn1, whose expression is limited to the skin and thymus epithelium. Our previous studies showed that Foxn1 inactivity in nude mice creates a pro-regenerative environment during skin wound healing. To explore the mechanistic role of Foxn1 in the skin wound healing process, we analyzed post-injured skin tissues from Foxn1::Egfp transgenic and C57BL/6 mice with Western Blotting, qRT-PCR, immunofluorescence and flow cytometric assays. Foxn1 expression in non-injured skin localized to the epidermis and hair follicles. Post-injured skin tissues showed an intense Foxn1-eGFP signal at the wound margin and in leading epithelial tongue, where it co-localized with keratin 16, a marker of activated keratinocytes. This data support the concept that suprabasal keratinocytes, expressing Foxn1, are key cells in the process of re-epithelialization. The occurrence of an epithelial-mesenchymal transition (EMT was confirmed by high levels of Snail1 and Mmp-9 expression as well as through co-localization of vimentin/E-cadherin-positive cells in dermis tissue at four days post-wounding. Involvement of Foxn1 in the EMT process was verified by co-localization of Foxn1-eGFP cells with Snail1 in histological sections. Flow cytometric analysis showed the increase of double positive E-cadherin/N-cadherin cells within Foxn1-eGFP population of post-wounded skin cells isolates, which corroborated histological and gene expression analyses. Together, our findings indicate that Foxn1 acts as regulator of the skin wound healing process through engagement in re-epithelization and possible involvement in scar formation due to Foxn1 activity during the EMT process.

  7. Dietary fatty acid content regulates wound repair and the pathogenesis of osteoarthritis following joint injury.

    Science.gov (United States)

    Wu, Chia-Lung; Jain, Deeptee; McNeill, Jenna N; Little, Dianne; Anderson, John A; Huebner, Janet L; Kraus, Virginia B; Rodriguiz, Ramona M; Wetsel, William C; Guilak, Farshid

    2015-11-01

    The mechanisms linking obesity and osteoarthritis (OA) are not fully understood and have been generally attributed to increased weight, rather than metabolic or inflammatory factors. Here, we examined the influence of fatty acids, adipokines, and body weight on OA following joint injury in an obese mouse model. Mice were fed high-fat diets rich in various fatty acids (FA) including saturated FAs (SFAs), ω-6 polyunsaturated FAs (PUFAs), and ω-3 PUFAs. OA was induced by destabilising the medial meniscus. Wound healing was evaluated using an ear punch. OA, synovitis and wound healing were determined histologically, while bone changes were measured using microCT. Activity levels and serum cytokines were measured at various time-points. Multivariate models were performed to elucidate the associations of dietary, metabolic and mechanical factors with OA and wound healing. Using weight-matched mice and multivariate models, we found that OA was significantly associated with dietary fatty acid content and serum adipokine levels, but not with body weight. Furthermore, spontaneous activity of the mice was independent of OA development. Small amounts of ω-3 PUFAs (8% by kcal) in a high-fat diet were sufficient to mitigate injury-induced OA, decreasing leptin and resistin levels. ω-3 PUFAs significantly enhanced wound repair, SFAs or ω-6 PUFAs independently increased OA severity, heterotopic ossification and scar tissue formation. Our results indicate that with obesity, dietary FA content regulates wound healing and OA severity following joint injury, independent of body weight, supporting the need for further studies of dietary FA supplements as a potential therapeutic approach for OA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  8. Immunodepletion of high-abundant proteins from acute and chronic wound fluids to elucidate low-abundant regulators in wound healing

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    Chojnacki Caroline

    2010-12-01

    Full Text Available Abstract Background The process of wound healing consists of several well distinguishable and finely tuned phases. For most of these phases specific proteins have been characterized, although the underlying mechanisms of regulation are not yet fully understood. It is an open question as to whether deficits in wound healing can be traced back to chronic illnesses such as diabetes mellitus. Previous research efforts in this field focus largely on a restricted set of marker proteins due to the limitations detection by antibodies imposes. For mechanistic purposes the elucidation of differences in acute and chronic wounds can be addressed by a less restricted proteome study. Mass spectrometric (MS methods, e.g. multi dimensional protein identification technology (MudPIT, are well suitable for this complex theme of interest. The human wound fluid proteome is extremely complex, as is human plasma. Therefore, high-abundant proteins often mask the mass spectrometric detection of lower-abundant ones, which makes a depletion step of such predominant proteins inevitable. Findings In this study a commercially available immunodepletion kit was evaluated for the detection of low-abundant proteins from wound fluids. The dynamic range of the entire workflow was significantly increased to 5-6 orders of magnitude, which makes low-abundant regulatory proteins involved in wound healing accessible for MS detection. Conclusion The depletion of abundant proteins is absolutely necessary in order to analyze highly complex protein mixtures such as wound fluids using mass spectrometry. For this the used immunodepletion kit is a first but important step in order to represent the entire dynamic range of highly complex protein mixtures in the future.

  9. Wounding induces changes in cytokinin and auxin content in potato tuber, but does not induce formation of gibberellins

    Science.gov (United States)

    Cytokinin, auxin and gibberellin content in resting and wound-responding potato tuber are not clearly defined. Consequently, the coordination and possible networking of these classical hormones in the regulation of wound-healing processes are poorly understood. Using a well-defined tuber wound-hea...

  10. Matrix metalloproteinase-8 regulates transforming growth factor-β1 levels in mouse tongue wounds and fibroblasts in vitro.

    Science.gov (United States)

    Aström, Pirjo; Pirilä, Emma; Lithovius, Riitta; Heikkola, Heidi; Korpi, Jarkko T; Hernández, Marcela; Sorsa, Timo; Salo, Tuula

    2014-10-15

    Matrix metalloproteinase-8 (MMP-8)-deficient mice (Mmp8-/-) exhibit delayed dermal wound healing, but also partly contradicting results have been reported. Using the Mmp8-/- mice we investigated the role of MMP-8 in acute wound healing of the mobile tongue, and analyzed the function of tongue fibroblasts in vitro. Interestingly, in the early phase the tongue wounds of Mmp8-/- mice healed faster than those of wild type (wt) mice resulting in significant difference in wound widths (P=0.001, 6-24h). The Mmp8-/- wounds showed no change in myeloperoxidase positive myeloid cell count, but the level of transforming growth factor (TGF)-β1 was significantly increased (P=0.007) compared to the wt tongues. Fibroblasts cultured from wt tongues expressed MMP-8 and TGF-β1. However, higher TGF-β1 levels were detected in Mmp8-/- fibroblasts, and MMP-8 treatment decreased phosphorylated Smad-2 levels and α-smooth muscle actin expression in these fibroblasts suggesting reduced TGF-β1 signaling. Consistently, a degradation of recombinant TGF-β1 by MMP-8 decreased its ability to activate the signaling cascade in fibroblasts. Moreover, collagen gels with Mmp8-/- fibroblasts reduced more in size. We conclude that MMP-8 regulates tongue wound contraction rate and TGF-β1 levels. In vitro analyses suggest that MMP-8 may also play a role in regulating TGF-β1 signaling of stromal fibroblasts. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Coordinate regulation of lipid metabolism by novel nuclear receptor partnerships.

    Directory of Open Access Journals (Sweden)

    Pranali P Pathare

    Full Text Available Mammalian nuclear receptors broadly influence metabolic fitness and serve as popular targets for developing drugs to treat cardiovascular disease, obesity, and diabetes. However, the molecular mechanisms and regulatory pathways that govern lipid metabolism remain poorly understood. We previously found that the Caenorhabditis elegans nuclear hormone receptor NHR-49 regulates multiple genes in the fatty acid beta-oxidation and desaturation pathways. Here, we identify additional NHR-49 targets that include sphingolipid processing and lipid remodeling genes. We show that NHR-49 regulates distinct subsets of its target genes by partnering with at least two other distinct nuclear receptors. Gene expression profiles suggest that NHR-49 partners with NHR-66 to regulate sphingolipid and lipid remodeling genes and with NHR-80 to regulate genes involved in fatty acid desaturation. In addition, although we did not detect a direct physical interaction between NHR-49 and NHR-13, we demonstrate that NHR-13 also regulates genes involved in the desaturase pathway. Consistent with this, gene knockouts of these receptors display a host of phenotypes that reflect their gene expression profile. Our data suggest that NHR-80 and NHR-13's modulation of NHR-49 regulated fatty acid desaturase genes contribute to the shortened lifespan phenotype of nhr-49 deletion mutant animals. In addition, we observed that nhr-49 animals had significantly altered mitochondrial morphology and function, and that distinct aspects of this phenotype can be ascribed to defects in NHR-66- and NHR-80-mediated activities. Identification of NHR-49's binding partners facilitates a fine-scale dissection of its myriad regulatory roles in C. elegans. Our findings also provide further insights into the functions of the mammalian lipid-sensing nuclear receptors HNF4α and PPARα.

  12. Driving Skills of Young Adults with Developmental Coordination Disorder: Regulating Speed and Coping with Distraction

    Science.gov (United States)

    de Oliveira, Rita F.; Wann, John P.

    2011-01-01

    In two experiments, we used an automatic car simulator to examine the steering control, speed regulation and response to hazards of young adults with developmental coordination disorder (DCD) and limited driving experience. In Experiment 1 participants either used the accelerator pedal to regulate their speed, or used the brake pedal when they…

  13. Role of non-mulberry silk fibroin in deposition and regulation of extracellular matrix towards accelerated wound healing.

    Science.gov (United States)

    Chouhan, Dimple; Chakraborty, Bijayshree; Nandi, Samit K; Mandal, Biman B

    2017-01-15

    Bombyx mori silk fibroin (BMSF) as biopolymer has been extensively explored in wound healing applications. However, limited study is available on the potential of silk fibroin (SF) from non-mulberry (Antheraea assama and Philosamia ricini) silk variety. Herein, we have developed non-mulberry SF (NMSF) based electrospun mats functionalized with epidermal growth factor (EGF) and ciprofloxacin HCl as potential wound dressing. The NMSF based mats exhibited essential properties of wound dressing like biocompatibility, high water retention capacity (440%), water vapor transmission rate (∼2330gm-2day-1), high elasticity (∼2.6MPa), sustained drug release and antibacterial activity. Functionalized NMSF mats enhanced the proliferation of human dermal fibroblasts and HaCaT cells in vitro as compared to non-functionalized mats (p⩽0.01) showing effective delivery of EGF. Extensive in vivo wound healing assesment demonstrated accelerated wound healing, enhanced re-epithelialization, highly vascularized granulation tissue and higher wound maturity as compared to BMSF based mats. NMSF mats treated wounds showed regulated deposition of mature elastin, collagen and reticulin fibers in the extracellular matrix of skin. Presence of skin appendages and isotropic collagen fibers in the regenerated skin also demonstrated scar-less healing and aesthetic wound repair. A facile fabrication of a ready-to-use bioactive wound dressing capable of concomitantly accelerating the healing process as well as deposition of the extracellular matrix (ECM) to circumvent further scarring complicacies has become a focal point of research. In this backdrop, our present work is based on non-mulberry silk fibroin (NMSF) electrospun antibiotic loaded semi-occlusive mats, mimicking the ECM of skin in terms of morphology, topology, microporous structure and mechanical stiffness. Regulation of ECM deposition and isotropic orientation evinced the potential of the mat as an instructive platform for skin

  14. Reactive oxygen species-dependent wound responses in animals and plants.

    Science.gov (United States)

    Suzuki, Nobuhiro; Mittler, Ron

    2012-12-15

    Animals and plants evolved sophisticated mechanisms that regulate their responses to mechanical injury. Wound response in animals mainly promotes wound healing processes, nerve cell regeneration, and immune system responses at the vicinity of the wound site. In contrast, wound response in plants is primarily directed at sealing the wound site via deposition of various compounds and generating systemic signals that activate multiple defense mechanisms in remote tissues. Despite these differences between animals and plants, recent studies have shown that reactive oxygen species (ROS) play very common signaling and coordination roles in the wound responses of both systems. This review provides an update on recent findings related to ROS-regulated coordination of intercellular communications and signal transduction during wound response in plants and animals. In particular, differences and similarities in H2O2-dependent long-distance signaling between zebrafish and Arabidopsis thaliana are discussed. Published by Elsevier Inc.

  15. Boron transport in plants: co-ordinated regulation of transporters

    Science.gov (United States)

    Miwa, Kyoko; Fujiwara, Toru

    2010-01-01

    Background The essentiality of boron (B) for plant growth was established >85 years ago. In the last decade, it has been revealed that one of the physiological roles of B is cross-linking the pectic polysaccharide rhamnogalacturonan II in primary cell walls. Borate cross-linking of pectic networks serves both for physical strength of cell walls and for cell adhesion. On the other hand, high concentrations of B are toxic to plant growth. To avoid deficiency and toxicity problems, it is important for plants to maintain their tissue B concentrations within an optimum range by regulating transport processes. Boron transport was long believed to be a passive, unregulated process, but the identification of B transporters has suggested that plants sense and respond to the B conditions and regulate transporters to maintain B homeostasis. Scope Transporters responsible for efficient B uptake by roots, xylem loading and B distribution among leaves have been described. These transporters are required under B limitation for efficient acquisition and utilization of B. Transporters important for tolerating high B levels in the environment have also been identified, and these transporters export B from roots back to the soil. Two types of transporters are involved in these processes: NIPs (nodulin-26-like intrinsic proteins), boric acid channels, and BORs, B exporters. It is demonstrated that the expression of genes encoding these transporters is finely regulated in response to B availability in the environment to ensure tissue B homeostasis. Furthermore, plants tolerant to stress produced by low B or high B in the environment can be generated through altered expression of these transporters. Conclusions The identification of the first B transporter led to the discovery that B transport was a process mediated not only by passive diffusion but also by transporters whose activity was regulated in response to B conditions. Now it is evident that plants sense internal and external B

  16. IκB kinase β regulates epithelium migration during corneal wound healing.

    Directory of Open Access Journals (Sweden)

    Liang Chen

    2011-01-01

    Full Text Available The IKKβ is known to regulate transcription factor NF-κB activation leading to inflammatory responses. Recent gene knockout studies have shown that IKKβ can orchestrate local inflammatory responses and regulate homeostasis of epithelial tissues. To investigate whether IKKβ has an intrinsic role in epithelial cells, we established an in vivo system in the immune privileged corneal epithelium. We generated triple transgenic Krt12(rtTA/rtTAt/tet-O-Cre/Ikkβ(F/F (Ikkβ(ΔCE/ΔCE mice by crossing the Krt12-rtTA knock-in mice, which express the reverse tetracycline transcription activator in corneal epithelial cells, with the tet-O-Cre and Ikkβ(F/F mice. Doxycycline-induced IKKβ ablation occurred in corneal epithelial cells of triple transgenic Ikkβ(ΔCE/ΔCE mice, but loss of IKKβ did not cause ocular abnormalities in fetal development and postnatal maintenance. Instead, loss of IKKβ significantly delayed healing of corneal epithelial debridement without affecting cell proliferation, apoptosis or macrophage infiltration. In vitro studies with human corneal epithelial cells (HCEpi also showed that IKKβ was required for cytokine-induced cell migration and wound closure but was dispensable for cell proliferation. In both in vivo and in vitro settings, IKKβ was required for optimal activation of NF-κB and p38 signaling in corneal epithelial cells, and p38 activation is likely mediated through formation of an IKKβ-p38 protein complex. Thus, our studies in corneal epithelium reveal a previously un-recognized role for IKKβ in the control of epithelial cell motility and wound healing.

  17. Regulation of TH17 Cells and Associated Cytokines in Wound Healing, Tissue Regeneration, and Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Leonie Brockmann

    2017-05-01

    Full Text Available Wound healing is a crucial process which protects our body against permanent damage and invasive infectious agents. Upon tissue damage, inflammation is an early event which is orchestrated by a multitude of innate and adaptive immune cell subsets including TH17 cells. TH17 cells and TH17 cell associated cytokines can impact wound healing positively by clearing pathogens and modulating mucosal surfaces and epithelial cells. Injury of the gut mucosa can cause fast expansion of TH17 cells and their induction from naïve T cells through Interleukin (IL-6, TGF-β, and IL-1β signaling. TH17 cells produce various cytokines, such as tumor necrosis factor (TNF-α, IL-17, and IL-22, which can promote cell survival and proliferation and thus tissue regeneration in several organs including the skin, the intestine, and the liver. However, TH17 cells are also potentially pathogenic if not tightly controlled. Failure of these control mechanisms can result in chronic inflammatory conditions, such as Inflammatory Bowel Disease (IBD, and can ultimately promote carcinogenesis. Therefore, there are several mechanisms which control TH17 cells. One control mechanism is the regulation of TH17 cells via regulatory T cells and IL-10. This mechanism is especially important in the intestine to terminate immune responses and maintain homeostasis. Furthermore, TH17 cells have the potential to convert from a pro-inflammatory phenotype to an anti-inflammatory phenotype by changing their cytokine profile and acquiring IL-10 production, thereby limiting their own pathological potential. Finally, IL-22, a signature cytokine of TH17 cells, can be controlled by an endogenous soluble inhibitory receptor, Interleukin 22 binding protein (IL-22BP. During tissue injury, the production of IL-22 by TH17 cells is upregulated in order to promote tissue regeneration. To limit the regenerative program, which could promote carcinogenesis, IL-22BP is upregulated during the later phase of

  18. Circadian rhythms accelerate wound healing in female Siberian hamsters.

    Science.gov (United States)

    Cable, Erin J; Onishi, Kenneth G; Prendergast, Brian J

    2017-03-15

    Circadian rhythms (CRs) provide temporal regulation and coordination of numerous physiological traits, including immune function. CRs in multiple aspects of immune function are impaired in rodents that have been rendered circadian-arrhythmic through various methods. In Siberian hamsters, circadian arrhythmia can be induced by disruptive light treatments (DPS). Here we examined CRs in wound healing, and the effects of circadian disruption on wound healing in DPS-arrhythmic hamsters. Circadian entrained/rhythmic (RHYTH) and behaviorally-arrhythmic (ARR) female hamsters were administered a cutaneous wound either 3h after light onset (ZT03) or 2h after dark onset (ZT18); wound size was quantified daily using image analyses. Among RHYTH hamsters, ZT03 wounds healed faster than ZT18 wounds, whereas in ARR hamsters, circadian phase did not affect wound healing. In addition, wounds healed slower in ARR hamsters. The results document a clear CR in wound healing, and indicate that the mere presence of organismal circadian organization enhances this aspect of immune function. Faster wound healing in CR-competent hamsters may be mediated by CR-driven coordination of the temporal order of mechanisms (inflammation, leukocyte trafficking, tissue remodeling) underlying cutaneous wound healing. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Directional cell migration and chemotaxis in wound healing response to PDGF-AA are coordinated by the primary cilium in fibroblasts

    DEFF Research Database (Denmark)

    Schneider, Linda; Cammer, Michael; Lehman, Jonathan

    2010-01-01

    Cell motility and migration play pivotal roles in numerous physiological and pathophysiological processes including development and tissue repair. Cell migration is regulated through external stimuli such as platelet-derived growth factor-AA (PDGF-AA), a key regulator in directional cell migration....... Here we used micropipette analysis to show that a normal chemosensory response to PDGF-AA in fibroblasts requires the primary cilium. In vitro and in vivo wound healing assays revealed that in ORPK mouse (IFT88(Tg737Rpw)) fibroblasts, where ciliary assembly is defective, chemotaxis towards PDGF-AA...

  20. Exosome production and its regulation of EGFR during wound healing in renal tubular cells.

    Science.gov (United States)

    Zhou, Xiangjun; Zhang, Wei; Yao, Qisheng; Zhang, Hao; Dong, Guie; Zhang, Ming; Liu, Yutao; Chen, Jian-Kang; Dong, Zheng

    2017-06-01

    Kidney repair following injury involves the reconstitution of a structurally and functionally intact tubular epithelium. Growth factors and their receptors, such as EGFR, are important in the repair of renal tubules. Exosomes are cell-produced small (~100 nm in diameter) vesicles that contain and transfer proteins, lipids, RNAs, and DNAs between cells. In this study, we examined the relationship between exosome production and EGFR activation and the potential role of exosome in wound healing. EGFR activation occurred shortly after scratch wounding in renal tubular cells. Wound repair after scratching was significantly promoted by EGF and suppressed by EGFR inhibitor gefitinib. Interestingly, scratch wounding induced a significant increase of exosome production. The exosome production was decreased by EGF and increased by gefitinib, suggesting a suppressive role of EGFR signaling in exosome production. Conversely, inhibition of exosome release by GW4869 and manumycin A markedly increased EGFR activation and promoted wound healing. Moreover, exosomes derived from scratch-wounding cells could inhibit wound healing. Collectively, the results indicate that wound healing in renal tubular cells is associated with EGFR activation and exosome production. Although EGFR activation promotes wound healing, released exosomes may antagonize EGFR activation and wound healing. Copyright © 2017 the American Physiological Society.

  1. Soft Regulation with Crowd Recommendation: Coordinating Self-Interested Agents in Sociotechnical Systems under Imperfect Information.

    Science.gov (United States)

    Luo, Yu; Iyengar, Garud; Venkatasubramanian, Venkat

    2016-01-01

    Regulating emerging industries is challenging, even controversial at times. Under-regulation can result in safety threats to plant personnel, surrounding communities, and the environment. Over-regulation may hinder innovation, progress, and economic growth. Since one typically has limited understanding of, and experience with, the novel technology in practice, it is difficult to accomplish a properly balanced regulation. In this work, we propose a control and coordination policy called soft regulation that attempts to strike the right balance and create a collective learning environment. In soft regulation mechanism, individual agents can accept, reject, or partially accept the regulator's recommendation. This non-intrusive coordination does not interrupt normal operations. The extent to which an agent accepts the recommendation is mediated by a confidence level (from 0 to 100%). Among all possible recommendation methods, we investigate two in particular: the best recommendation wherein the regulator is completely informed and the crowd recommendation wherein the regulator collects the crowd's average and recommends that value. We show by analysis and simulations that soft regulation with crowd recommendation performs well. It converges to optimum, and is as good as the best recommendation for a wide range of confidence levels. This work sheds a new theoretical perspective on the concept of the wisdom of crowds.

  2. Soft Regulation with Crowd Recommendation: Coordinating Self-Interested Agents in Sociotechnical Systems under Imperfect Information.

    Directory of Open Access Journals (Sweden)

    Yu Luo

    Full Text Available Regulating emerging industries is challenging, even controversial at times. Under-regulation can result in safety threats to plant personnel, surrounding communities, and the environment. Over-regulation may hinder innovation, progress, and economic growth. Since one typically has limited understanding of, and experience with, the novel technology in practice, it is difficult to accomplish a properly balanced regulation. In this work, we propose a control and coordination policy called soft regulation that attempts to strike the right balance and create a collective learning environment. In soft regulation mechanism, individual agents can accept, reject, or partially accept the regulator's recommendation. This non-intrusive coordination does not interrupt normal operations. The extent to which an agent accepts the recommendation is mediated by a confidence level (from 0 to 100%. Among all possible recommendation methods, we investigate two in particular: the best recommendation wherein the regulator is completely informed and the crowd recommendation wherein the regulator collects the crowd's average and recommends that value. We show by analysis and simulations that soft regulation with crowd recommendation performs well. It converges to optimum, and is as good as the best recommendation for a wide range of confidence levels. This work sheds a new theoretical perspective on the concept of the wisdom of crowds.

  3. Identification of a cis-regulatory element by transient analysis of co-ordinately regulated genes

    Directory of Open Access Journals (Sweden)

    Allan Andrew C

    2008-07-01

    Full Text Available Abstract Background Transcription factors (TFs co-ordinately regulate target genes that are dispersed throughout the genome. This co-ordinate regulation is achieved, in part, through the interaction of transcription factors with conserved cis-regulatory motifs that are in close proximity to the target genes. While much is known about the families of transcription factors that regulate gene expression in plants, there are few well characterised cis-regulatory motifs. In Arabidopsis, over-expression of the MYB transcription factor PAP1 (PRODUCTION OF ANTHOCYANIN PIGMENT 1 leads to transgenic plants with elevated anthocyanin levels due to the co-ordinated up-regulation of genes in the anthocyanin biosynthetic pathway. In addition to the anthocyanin biosynthetic genes, there are a number of un-associated genes that also change in expression level. This may be a direct or indirect consequence of the over-expression of PAP1. Results Oligo array analysis of PAP1 over-expression Arabidopsis plants identified genes co-ordinately up-regulated in response to the elevated expression of this transcription factor. Transient assays on the promoter regions of 33 of these up-regulated genes identified eight promoter fragments that were transactivated by PAP1. Bioinformatic analysis on these promoters revealed a common cis-regulatory motif that we showed is required for PAP1 dependent transactivation. Conclusion Co-ordinated gene regulation by individual transcription factors is a complex collection of both direct and indirect effects. Transient transactivation assays provide a rapid method to identify direct target genes from indirect target genes. Bioinformatic analysis of the promoters of these direct target genes is able to locate motifs that are common to this sub-set of promoters, which is impossible to identify with the larger set of direct and indirect target genes. While this type of analysis does not prove a direct interaction between protein and DNA

  4. Non-Cooperative Regulation Coordination Based on Game Theory for Wind Farm Clusters during Ramping Events

    DEFF Research Database (Denmark)

    Qi, Yongzhi; Liu, Yutian; Wu, Qiuwei

    2017-01-01

    With increasing penetration of wind power in power systems, it is important to track scheduled wind power output as much as possible during ramping events to ensure security of the system. In this paper, a non‐cooperative coordination strategy based on the game theory is proposed for the regulation...... of wind farm clusters (WFCs) in order to track scheduled wind power of the WFC during ramping events. In the proposed strategy, a non‐cooperative game is formulated and wind farms compete to provide regulation to the WFC during ramping events. A regulation revenue function is proposed to evaluate...

  5. Up-Regulated Expression of AOS-LOXa and Increased Eicosanoid Synthesis in Response to Coral Wounding

    Science.gov (United States)

    Lõhelaid, Helike; Teder, Tarvi; Tõldsepp, Kadri; Ekins, Merrick; Samel, Nigulas

    2014-01-01

    In octocorals, a catalase–like allene oxide synthase (AOS) and an 8R-lipoxygenase (LOX) gene are fused together encoding for a single AOS-LOX fusion protein. Although the AOS-LOX pathway is central to the arachidonate metabolism in corals, its biological function in coral homeostasis is unclear. Using an acute incision wound model in the soft coral Capnella imbricata, we here test whether LOX pathway, similar to its role in plants, can contribute to the coral damage response and regeneration. Analysis of metabolites formed from exogenous arachidonate before and after fixed time intervals following wounding indicated a significant increase in AOS-LOX activity in response to mechanical injury. Two AOS-LOX isoforms, AOS-LOXa and AOS-LOXb, were cloned and expressed in bacterial expression system as active fusion proteins. Transcription levels of corresponding genes were measured in normal and stressed coral by qPCR. After wounding, AOS-LOXa was markedly up-regulated in both, the tissue adjacent to the incision and distal parts of a coral colony (with the maximum reached at 1 h and 6 h post wounding, respectively), while AOS-LOXb was stable. According to mRNA expression analysis, combined with detection of eicosanoid product formation for the first time, the AOS-LOX was identified as an early stress response gene which is induced by mechanical injury in coral. PMID:24551239

  6. Detecting coordinated regulation of multi-protein complexes using logic analysis of gene expression

    Directory of Open Access Journals (Sweden)

    Yeates Todd O

    2009-12-01

    Full Text Available Abstract Background Many of the functional units in cells are multi-protein complexes such as RNA polymerase, the ribosome, and the proteasome. For such units to work together, one might expect a high level of regulation to enable co-appearance or repression of sets of complexes at the required time. However, this type of coordinated regulation between whole complexes is difficult to detect by existing methods for analyzing mRNA co-expression. We propose a new methodology that is able to detect such higher order relationships. Results We detect coordinated regulation of multiple protein complexes using logic analysis of gene expression data. Specifically, we identify gene triplets composed of genes whose expression profiles are found to be related by various types of logic functions. In order to focus on complexes, we associate the members of a gene triplet with the distinct protein complexes to which they belong. In this way, we identify complexes related by specific kinds of regulatory relationships. For example, we may find that the transcription of complex C is increased only if the transcription of both complex A AND complex B is repressed. We identify hundreds of examples of coordinated regulation among complexes under various stress conditions. Many of these examples involve the ribosome. Some of our examples have been previously identified in the literature, while others are novel. One notable example is the relationship between the transcription of the ribosome, RNA polymerase and mannosyltransferase II, which is involved in N-linked glycan processing in the Golgi. Conclusions The analysis proposed here focuses on relationships among triplets of genes that are not evident when genes are examined in a pairwise fashion as in typical clustering methods. By grouping gene triplets, we are able to decipher coordinated regulation among sets of three complexes. Moreover, using all triplets that involve coordinated regulation with the ribosome

  7. DETERMINED MODEL FOR COORDINATED REGULATION OF MOTOR TRANSPORT MOVEMENT ON HIGHWAY WITH T-SHAPE CROSSROADS

    Directory of Open Access Journals (Sweden)

    V. N. Shut

    2009-01-01

    Full Text Available The paper examines variants of higher control efficiency in respect of road traffic by creating coordinated regulation  with the help of a determined module. Model application conditions have been determined for specific traffic situations with due account of transport-pedestrian load. The paper contains proposals for the model optimization directed on reduction of  motor vehicle delay in front of the in-traffic light  stop-line along the main highway direction.

  8. The oncogene c-Myc coordinates regulation of metabolic networks to enable rapid cell cycle entry.

    Science.gov (United States)

    Morrish, Fionnuala; Neretti, Nicola; Sedivy, John M; Hockenbery, David M

    2008-04-15

    The c-myc proto-oncogene is rapidly activated by serum and regulates genes involved in metabolism and cell cycle progression. This gene is thereby uniquely poised to coordinate both the metabolic and cell cycle regulatory events required for cell cycle entry. However, this function of Myc has not been evaluated. Using a rat fibroblast model of isogenic cell lines, myc(-/-), myc(+/-), myc(+/+) and myc(-/-) cells with an inducible c-myc transgene (mycER), we show that the Myc protein programs cells to utilize both oxidative phosphorylation and glycolysis to drive cell cycle progression. We demonstrate this coordinate regulation of metabolic networks is essential, as specific inhibitors of these pathways block Myc-induced proliferation. Metabolic events temporally correlated with cell cycle entry include increased oxygen consumption, mitochondrial function, pyruvate and lactate production, and ATP generation. Treatment of normal cells with inhibitors of oxidative phosphorylation recapitulates the myc(-/-) phenotype, resulting in impaired cell cycle entry and reduced metabolism. Combined with a kinetic expression profiling analysis of genes linked to mitochondrial function, our study indicates that Myc's ability to coordinately regulate the mitochondrial metabolic network transcriptome is required for rapid cell cycle entry. This function of Myc may underlie the pervasive presence of Myc in many human cancers.

  9. Sheng-ji Hua-yu formula promotes diabetic wound healing of re-epithelization via Activin/Follistatin regulation.

    Science.gov (United States)

    Kuai, Le; Zhang, Jing-Ting; Deng, Yu; Xu, Shun; Xu, Xun-Zhe; Wu, Min-Feng; Guo, Dong-Jie; Chen, Yu; Wu, Ren-Jie; Zhao, Xing-Qiang; Nian, Hua; Li, Bin; Li, Fu-Lun

    2018-01-29

    Sheng-ji Hua-yu(SJHY) formula is one of the most useful Traditional Chinese medicine (TCM) in the treatment of the delayed diabetic wound. However, elucidating the related molecular biological mechanism of how the SJHY Formula affects excessive inflammation in the process of re-epithelialization of diabetic wound healing is a task urgently needed to be fulfilled. The objectives of this study is to evaluate the effect of antagonisic expression of pro-/anti-inflammatory factors on transforming growth factor-β(TGF-β) superfamily (activin and follistatin) in the process of re-epithelialization of diabetic wound healing in vivo, and to characterize the involvement of the activin/follistatin protein expression regulation, phospho-Smad (pSmad2), and Nuclear factor kappa B p50 (NF-kB) p50 in the diabetic wound healing effects of SJHY formula. SJHY Formula was prepared by pharmaceutical preparation room of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine. Diabetic wound healing activity was evaluated by circular excision wound models. Wound healing activity was examined by macroscopic evaluation. Activin/follistatin expression regulation, protein expression of pSmad2 and NF-kB p50 in skin tissue of wounds were analyzed by Real Time PCR, Western blot, immunohistochemistry and hematoxylin and eosin (H&E) staining. Macroscopic evaluation analysis showed that wound healing of diabetic mice was delayed, and SJHY Formula accelerated wound healing time of diabetic mice. Real Time PCR analysis showed higher mRNA expression of activin/follistatin in diabetic delayed wound versus the wound in normal mice. Western Blot immunoassay analysis showed reduction of activin/follistatin proteins levels by SJHY Formula treatment 15 days after injury. Immunohistochemistry investigated the reduction of pSmad2 and NF-kB p50 nuclear staining in the epidermis of diabetic SJHY versus diabetic control mice on day 15 after wounding. H&E staining revealed that SJHY Formula

  10. Ube2w and ataxin-3 coordinately regulate the ubiquitin ligase CHIP

    Science.gov (United States)

    Scaglione, K. Matthew; Zavodszky, Eszter; Todi, Sokol V.; Patury, Srikanth; Xu, Ping; Rodríguez-Lebrón, Edgardo; Fischer, Svetlana; Konen, John; Djarmati, Ana; Peng, Junmin; Gestwicki, Jason E.; Paulson, Henry L.

    2011-01-01

    Summary The mechanisms by which ubiquitin ligases are regulated remain poorly understood. Here we describe a series of molecular events that coordinately regulate CHIP, a neuroprotective E3 implicated in protein quality control. Through their opposing activities, the initiator E2, Ube2w, and the specialized deubiquitinating enzyme (DUB), ataxin-3, participate in initiating, regulating and terminating the CHIP ubiquitination cycle. Monoubiquitination of CHIP by Ube2w stabilizes the interaction between CHIP and ataxin-3, which through its DUB activity limits the length of chains attached to CHIP substrates. Upon completion of substrate ubiquitination ataxin-3 deubiquitinates CHIP, effectively terminating the reaction. Our results suggest that functional pairing of E3s with ataxin-3 or similar DUBs represents an important point of regulation in ubiquitin-dependent protein quality control. In addition, the results shed light on disease pathogenesis in SCA3, a neurodegenerative disorder caused by polyglutamine expansion in ataxin-3. PMID:21855799

  11. Cooperative Regulation of Substrate Stiffness and Extracellular Matrix Proteins in Skin Wound Healing of Axolotls

    Directory of Open Access Journals (Sweden)

    Ting-Yu Huang

    2015-01-01

    Full Text Available Urodele amphibians (Ambystoma mexicanum, unique among vertebrates, can regenerate appendages and other body parts entirely and functionally through a scar-free healing process. The wound epithelium covering the amputated or damaged site forms early and is essential for initiating the subsequent regenerative steps. However, the molecular mechanism through which the wound reepithelializes during regeneration remains unclear. In this study, we developed an in vitro culture system that mimics an in vivo wound healing process; the biomechanical properties in the system were precisely defined and manipulated. Skin explants that were cultured on 2 to 50 kPa collagen-coated substrates rapidly reepithelialized within 10 to 15 h; however, in harder (1 GPa and other extracellular matrices (tenascin-, fibronectin-, and laminin-coated environments, the wound epithelium moved slowly. Furthermore, the reepithelialization rate of skin explants from metamorphic axolotls cultured on a polystyrene plate (1 GPa increased substantially. These findings afford new insights and can facilitate investigating wound epithelium formation during early regeneration using biochemical and mechanical techniques.

  12. Engineering Metal Ion Coordination to Regulate Amyloid Fibril Assembly And Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Dong, J.; Canfield, J.M.; Mehta, A.K.; Shokes, J.E.; Tian, B.; Childers, W.S.; Simmons, J.A.; Mao, Z.; Scott, R.A.; Warncke, K.; Lynn, D.G.

    2009-06-02

    Protein and peptide assembly into amyloid has been implicated in functions that range from beneficial epigenetic controls to pathological etiologies. However, the exact structures of the assemblies that regulate biological activity remain poorly defined. We have previously used Zn{sup 2+} to modulate the assembly kinetics and morphology of congeners of the amyloid {beta} peptide (A{beta}) associated with Alzheimer's disease. We now reveal a correlation among A{beta}-Cu{sup 2+} coordination, peptide self-assembly, and neuronal viability. By using the central segment of A{beta}, HHQKLVFFA or A{beta}(13-21), which contains residues H13 and H14 implicated in A{beta}-metal ion binding, we show that Cu{sup 2+} forms complexes with A{beta}(13-21) and its K16A mutant and that the complexes, which do not self-assemble into fibrils, have structures similar to those found for the human prion protein, PrP. N-terminal acetylation and H14A substitution, Ac-A{beta}(13-21)H14A, alters metal coordination, allowing Cu{sup 2+} to accelerate assembly into neurotoxic fibrils. These results establish that the N-terminal region of A{beta} can access different metal-ion-coordination environments and that different complexes can lead to profound changes in A{beta} self-assembly kinetics, morphology, and toxicity. Related metal-ion coordination may be critical to the etiology of other neurodegenerative diseases.

  13. Islet Coordinately Regulates Motor Axon Guidance and Dendrite Targeting through the Frazzled/DCC Receptor

    Directory of Open Access Journals (Sweden)

    Celine Santiago

    2017-02-01

    Full Text Available Motor neuron axon targeting in the periphery is correlated with the positions of motor neuron inputs in the CNS, but how these processes are coordinated to form a myotopic map remains poorly understood. We show that the LIM homeodomain factor Islet (Isl controls targeting of both axons and dendrites in Drosophila motor neurons through regulation of the Frazzled (Fra/DCC receptor. Isl is required for fra expression in ventrally projecting motor neurons, and isl and fra mutants have similar axon guidance defects. Single-cell labeling indicates that isl and fra are also required for dendrite targeting in a subset of motor neurons. Finally, overexpression of Fra rescues axon and dendrite targeting defects in isl mutants. These results indicate that Fra acts downstream of Isl in both the periphery and the CNS, demonstrating how a single regulatory relationship is used in multiple cellular compartments to coordinate neural circuit wiring.

  14. Inhibition of apoptosis signal-regulating kinase 1 alters the wound epidermis and enhances auricular cartilage regeneration.

    Directory of Open Access Journals (Sweden)

    Qian-Shi Zhang

    Full Text Available Why regeneration does not occur in mammals remains elusive. In lower vertebrates, epimorphic regeneration of the limb is directed by the wound epidermis, which controls blastema formation to promote regrowth of the appendage. Herein, we report that knockout (KO or inhibition of Apoptosis Signal-regulated Kinase-1 (ASK1, also known as mitogen-activated protein kinase kinase kinase 5 (MAP3K5, after full thickness ear punch in mice prolongs keratinocyte activation within the wound epidermis and promotes regeneration of auricular cartilage. Histological analysis showed the ASK1 KO ears displayed enhanced protein markers associated with blastema formation, hole closure and regeneration of auricular cartilage. At seven days after punch, the wound epidermis morphology was markedly different in the KO, showing a thickened stratum corneum with rounded cell morphology and a reduction of both the granular cell layer and decreased expression of filament aggregating protein. In addition, cytokeratin 6 was expressed in the stratum spinosum and granulosum. Topical application of inhibitors of ASK1 (NQDI-1, the upstream ASK1 activator, calcium activated mitogen kinase 2 (KN93, or the downstream target, c-Jun N-terminal kinase (SP600125 also resulted in enhanced regeneration; whereas inhibition of the other downstream target, the p38 α/β isoforms, (SB203580 had no effect. The results of this investigation indicate ASK1 inhibition prolongs keratinocyte and blastemal cell activation leading to ear regeneration.

  15. Inhibition of apoptosis signal-regulating kinase 1 alters the wound epidermis and enhances auricular cartilage regeneration.

    Science.gov (United States)

    Zhang, Qian-Shi; Kurpad, Deepa S; Mahoney, My G; Steinbeck, Marla J; Freeman, Theresa A

    2017-01-01

    Why regeneration does not occur in mammals remains elusive. In lower vertebrates, epimorphic regeneration of the limb is directed by the wound epidermis, which controls blastema formation to promote regrowth of the appendage. Herein, we report that knockout (KO) or inhibition of Apoptosis Signal-regulated Kinase-1 (ASK1), also known as mitogen-activated protein kinase kinase kinase 5 (MAP3K5), after full thickness ear punch in mice prolongs keratinocyte activation within the wound epidermis and promotes regeneration of auricular cartilage. Histological analysis showed the ASK1 KO ears displayed enhanced protein markers associated with blastema formation, hole closure and regeneration of auricular cartilage. At seven days after punch, the wound epidermis morphology was markedly different in the KO, showing a thickened stratum corneum with rounded cell morphology and a reduction of both the granular cell layer and decreased expression of filament aggregating protein. In addition, cytokeratin 6 was expressed in the stratum spinosum and granulosum. Topical application of inhibitors of ASK1 (NQDI-1), the upstream ASK1 activator, calcium activated mitogen kinase 2 (KN93), or the downstream target, c-Jun N-terminal kinase (SP600125) also resulted in enhanced regeneration; whereas inhibition of the other downstream target, the p38 α/β isoforms, (SB203580) had no effect. The results of this investigation indicate ASK1 inhibition prolongs keratinocyte and blastemal cell activation leading to ear regeneration.

  16. MicroRNAs-103/107 coordinately regulate macropinocytosis and autophagy.

    Science.gov (United States)

    Park, Jong Kook; Peng, Han; Katsnelson, Julia; Yang, Wending; Kaplan, Nihal; Dong, Ying; Rappoport, Joshua Z; He, CongCong; Lavker, Robert M

    2016-12-05

    Macropinocytosis, by which cells ingest large amounts of fluid, and autophagy, the lysosome-based catabolic process, involve vesicular biogenesis (early stage) and turnover (end stage). Much is known about early-stage events; however, our understanding of how the end stages of these processes are governed is incomplete. Here we demonstrate that the microRNA-103/107(miR-103/107) family, which is preferentially expressed in the stem cell-enriched limbal epithelium, coordinately regulates aspects of both these activities. Loss of miR-103/107 causes dysregulation of macropinocytosis with the formation of large vacuoles, primarily through up-regulation of Src, Ras, and Ankfy1. Vacuole accumulation is not a malfunction of early-stage autophagy; rather, miR-103/107 ensure proper end-stage autophagy by regulating diacylglycerol/protein kinase C and cyclin-dependent kinase 5 signaling, which enables dynamin to function in vacuole clearance. Our findings unveil a key biological function for miR-103/107 in coordinately suppressing macropinocytosis and preserving end-stage autophagy, thereby contributing to maintenance of a stem cell-enriched epithelium. © 2016 Park et al.

  17. Multi-dimensional histone methylations for coordinated regulation of gene expression under hypoxia.

    Science.gov (United States)

    Lee, Seongyeol; Lee, Jieon; Chae, Sehyun; Moon, Yunwon; Lee, Ho-Youl; Park, Bongju; Yang, Eun Gyeong; Hwang, Daehee; Park, Hyunsung

    2017-11-16

    Hypoxia increases both active and repressive histone methylation levels via decreased activity of histone demethylases. However, how such increases coordinately regulate induction or repression of hypoxia-responsive genes is largely unknown. Here, we profiled active and repressive histone tri-methylations (H3K4me3, H3K9me3, and H3K27me3) and analyzed gene expression profiles in human adipocyte-derived stem cells under hypoxia. We identified differentially expressed genes (DEGs) and differentially methylated genes (DMGs) by hypoxia and clustered the DEGs and DMGs into four major groups. We found that each group of DEGs was predominantly associated with alterations in only one type among the three histone tri-methylations. Moreover, the four groups of DEGs were associated with different TFs and localization patterns of their predominant types of H3K4me3, H3K9me3 and H3K27me3. Our results suggest that the association of altered gene expression with prominent single-type histone tri-methylations characterized by different localization patterns and with different sets of TFs contributes to regulation of particular sets of genes, which can serve as a model for coordinated epigenetic regulation of gene expression under hypoxia. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  18. Calcium oscillations in wounded fibroblast monolayers are spatially regulated through substrate mechanics

    Science.gov (United States)

    Lembong, Josephine; Sabass, Benedikt; Stone, Howard A.

    2017-08-01

    The maintenance of tissue integrity is essential for the life of multicellular organisms. Healing of a skin wound is a paradigm for how various cell types localize and repair tissue perturbations in an orchestrated fashion. To investigate biophysical mechanisms associated with wound localization, we focus on a model system consisting of a fibroblast monolayer on an elastic substrate. We find that the creation of an edge in the monolayer causes cytosolic calcium oscillations throughout the monolayer. The oscillation frequency increases with cell density, which shows that wound-induced calcium oscillations occur collectively. Inhibition of myosin II reduces the number of oscillating cells, demonstrating a coupling between actomyosin activity and calcium response. The spatial distribution of oscillating cells depends on the stiffness of the substrate. For soft substrates with a Young’s modulus E ~ 360 Pa, oscillations occur on average within 0.2 mm distance from the wound edge. Increasing substrate stiffness leads to an average localization of oscillations away from the edge (up to ~0.6 mm). In addition, we use traction force microscopy to determine stresses between cells and substrate. We find that an increase of substrate rigidity leads to a higher traction magnitude. For E    ~8 kPa, traction magnitude is on average almost uniform beneath the monolayer. Thus, the spatial occurrence of calcium oscillations correlates with the cell-substrate traction. Overall, the experiments with fibroblasts demonstrate a collective, chemomechanical localization mechanism at the edge of a wound with a potential physiological role.

  19. Coordinated Regulation of Virulence during Systemic Infection of Salmonella enterica serovar Typhimurium

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Hyunjin; McDermott, Jason E.; Porwollik, Steffen; Mcclelland, Michael; Heffron, Fred

    2009-02-20

    Salmonella must respond to a myriad of environmental cues during infection of a mouse and express specific subsets of genes in a temporal and spatial manner to subvert the host defense mechanisms but these regulatory pathways are poorly established. To unravel how micro-environmental signals are processed and integrated into coordinated action, we constructed in-frame non-polar deletions of 84 regulators inferred to play a role in Salmonella typhimurium virulence and tested them in three virulence assays (intraperitoneal (i.p.), and intragastric (i.g.) infection in BALB/c mice, and persistence in SvJ129 mice). Overall 36 regulators were identified that were less virulent in at least one assay, and of those, 15 regulators were required for systemic mouse infection in an acute infection model. As a first step towards understanding the interplay between a pathogen and its host from a systems biology standpoint we focused on these 15 genes. Transcriptional profiles were obtained for each of these 15 regulators from strains grown under four different environmental conditions. These results as well as publicly available transcriptional profiles were analyzed using both network inference and cluster analysis algorithms. The analysis predicts a regulatory network in which all 15 regulators control a specific set of genes necessary for Salmonella to cause systemic infection. We tested the regulatory model by expressing a subset of the regulators in trans and monitoring transcription of 7 known virulence factors located within Salmonella pathogenicity island 2 (SPI-2). These experiments validated the regulatory model and showed that, for these 7 genes, the response regulator SsrB and the marR type regulator SlyA co-regulate in a regulatory cascade by integrating multiple signals.

  20. Coordinated regulation of virulence during systemic infection of Salmonella enterica serovar Typhimurium.

    Directory of Open Access Journals (Sweden)

    Hyunjin Yoon

    2009-02-01

    Full Text Available To cause a systemic infection, Salmonella must respond to many environmental cues during mouse infection and express specific subsets of genes in a temporal and spatial manner, but the regulatory pathways are poorly established. To unravel how micro-environmental signals are processed and integrated into coordinated action, we constructed in-frame non-polar deletions of 83 regulators inferred to play a role in Salmonella enteriditis Typhimurium (STM virulence and tested them in three virulence assays (intraperitoneal [i.p.], and intragastric [i.g.] infection in BALB/c mice, and persistence in 129X1/SvJ mice. Overall, 35 regulators were identified whose absence attenuated virulence in at least one assay, and of those, 14 regulators were required for systemic mouse infection, the most stringent virulence assay. As a first step towards understanding the interplay between a pathogen and its host from a systems biology standpoint, we focused on these 14 genes. Transcriptional profiles were obtained for deletions of each of these 14 regulators grown under four different environmental conditions. These results, as well as publicly available transcriptional profiles, were analyzed using both network inference and cluster analysis algorithms. The analysis predicts a regulatory network in which all 14 regulators control the same set of genes necessary for Salmonella to cause systemic infection. We tested the regulatory model by expressing a subset of the regulators in trans and monitoring transcription of 7 known virulence factors located within Salmonella pathogenicity island 2 (SPI-2. These experiments validated the regulatory model and showed that the response regulator SsrB and the MarR type regulator, SlyA, are the terminal regulators in a cascade that integrates multiple signals. Furthermore, experiments to demonstrate epistatic relationships showed that SsrB can replace SlyA and, in some cases, SlyA can replace SsrB for expression of SPI-2 encoded

  1. Coordinated Voltage Control of Distributed PV Inverters for Voltage Regulation in Low Voltage Distribution Networks

    DEFF Research Database (Denmark)

    Nainar, Karthikeyan; Pokhrel, Basanta Raj; Pillai, Jayakrishnan Radhakrishna

    2017-01-01

    This paper reviews and analyzes the existing voltage control methods of distributed solar PV inverters to improve the voltage regulation and thereby the hosting capacity of a low-voltage distribution network. A novel coordinated voltage control method is proposed based on voltage sensitivity...... analysis, which is simple for computation and requires moderate automation and communication infrastructure. The proposed method is suitable for a hierarchical control structure where a supervisory controller has the provision to adapt the settings of local PV inverter controllers for overall system...

  2. Coordinated Voltage Control of Distributed PV Inverters for Voltage Regulation in Low Voltage Distribution Networks

    DEFF Research Database (Denmark)

    Nainar, Karthikeyan; Pokhrel, Basanta Raj; Pillai, Jayakrishnan Radhakrishna

    2017-01-01

    This paper reviews and analyzes the existing voltage control methods of distributed solar PV inverters to improve the voltage regulation and thereby the hosting capacity of a low-voltage distribution network. A novel coordinated voltage control method is proposed based on voltage sensitivity...... optimization. The proposed method is used to calculate the voltage bands and droop settings of PV inverters at each node by the supervisory controller. The local controller of each PV inverter implements the volt/var control and if necessary, the active power curtailment as per the received settings and based...... on measured local voltages. The advantage of the proposed method is that the calculated reactive power and active power droop settings enable fair contribution of the PV inverters at each node to the voltage regulation. Simulation studies are conducted using DigSilent Power factory software on a simplified...

  3. Wound healing protects against chemotherapy-induced alopecia in young rats via up-regulating interleukin-1β-mediated signaling

    Directory of Open Access Journals (Sweden)

    Olivera Stojadinovic

    2017-05-01

    Full Text Available Wound healing is a complex process regulated by various cell types and a plethora of mediators. While interactions between wounded skin and the hair follicles (HFs could induce HF neogenesis or promote wound healing, it remains unknown whether the wound healing-associated signaling milieu can be manipulated to protect against alopecia, such as chemotherapy-induced alopecia (CIA. Utilizing a well-established neonatal rat model of CIA, we show here that skin wounding protects from alopecia caused by several clinically relevant chemotherapeutic regimens, and that protection is dependent on the time of wounding and hair cycle stage. Gene expression profiling unveiled a significant increase in interleukin-1 beta (IL-1β mediated signaling by skin wounding. Subsequently, we showed that IL-1β is sufficient and indispensable for mediating the CIA-protective effect. Administration of IL-1β alone to unwounded rats exhibited local CIA protection while IL-1β neutralization abrogated CIA protection by wounding. Mechanistically, IL-1β retarded postnatal HF morphogenesis, making HFs at the wound sites or IL-1β treated areas damage-resistant while the rats developed total alopecia elsewhere. We conclude that wound healing switches the cutaneous cytokine milieu to an IL-1β-dominated state thus retarding HF growth progression and rendering the HFs resistant to chemotherapy agents. In the future, manipulation of HF progression through interfering with the IL-1β signaling milieu may provide therapeutic benefits to a variety of conditions, from prevention of CIA to inhibition of hair growth and treatment of hirsutism.

  4. bFGF regulates PI3-kinase-Rac1-JNK pathway and promotes fibroblast migration in wound healing.

    Directory of Open Access Journals (Sweden)

    Shigeyuki Kanazawa

    Full Text Available Fibroblast proliferation and migration play important roles in wound healing. bFGF is known to promote both fibroblast proliferation and migration during the process of wound healing. However, the signal transduction of bFGF-induced fibroblast migration is still unclear, because bFGF can affect both proliferation and migration. Herein, we investigated the effect of bFGF on fibroblast migration regardless of its effect on fibroblast proliferation. We noticed involvement of the small GTPases of the Rho family, PI3-kinase, and JNK. bFGF activated RhoA, Rac1, PI3-kinase, and JNK in cultured fibroblasts. Inhibition of RhoA did not block bFGF-induced fibroblast migration, whereas inhibition of Rac1, PI3-kinase, or JNK blocked the fibroblast migration significantly. PI3-kinase-inhibited cells down-regulated the activities of Rac1 and JNK, and Rac1-inhibited cells down-regulated JNK activity, suggesting that PI3-kinase is upstream of Rac1 and that JNK is downstream of Rac1. Thus, we concluded that PI3-kinase, Rac1, and JNK were essential for bFGF-induced fibroblast migration, which is a novel pathway of bFGF-induced cell migration.

  5. Rac Regulates Giardia lamblia Encystation by Coordinating Cyst Wall Protein Trafficking and Secretion.

    Science.gov (United States)

    Krtková, Jana; Thomas, Elizabeth B; Alas, Germain C M; Schraner, Elisabeth M; Behjatnia, Habib R; Hehl, Adrian B; Paredez, Alexander R

    2016-08-23

    Encystation of the common intestinal parasite Giardia lamblia involves the production, trafficking, and secretion of cyst wall material (CWM). However, the molecular mechanism responsible for the regulation of these sequential processes remains elusive. Here, we examined the role of GlRac, Giardia's sole Rho family GTPase, in the regulation of endomembrane organization and cyst wall protein (CWP) trafficking. Localization studies indicated that GlRac is associated with the endoplasmic reticulum (ER) and the Golgi apparatus-like encystation-specific vesicles (ESVs). Constitutive GlRac signaling increased levels of the ER marker PDI2, induced ER swelling, reduced overall CWP1 production, and promoted the early maturation of ESVs. Quantitative analysis of cells expressing constitutively active hemagglutinin (HA)-tagged GlRac (HA-Rac(CA)) revealed fewer but larger ESVs than control cells. Consistent with the phenotype of premature maturation of ESVs in HA-Rac(CA)-expressing cells, constitutive GlRac signaling resulted in increased CWP1 secretion and, conversely, morpholino depletion of GlRac blocked CWP1 secretion. Wild-type cells unexpectedly secreted large quantities of CWP1 into the medium, and free CWP1 was used cooperatively during cyst formation. These results, in part, could account for the previously reported observation that G. lamblia encysts more efficiently at high cell densities. These studies of GlRac show that it regulates encystation at several levels, and our findings support its coordinating role as a regulator of CWP trafficking and secretion. The central role of GlRac in regulating membrane trafficking and the cytoskeleton, both of which are essential to Giardia parasitism, further suggests its potential as a novel target for drug development to treat giardiasis. The encystation process is crucial for the transmission of giardiasis and the life cycle of many protists. Encystation for Giardia lamblia involves the assembly of a protective cyst wall

  6. Coordinated Evolution of Transcriptional and Post-Transcriptional Regulation for Mitochondrial Functions in Yeast Strains.

    Directory of Open Access Journals (Sweden)

    Xuepeng Sun

    Full Text Available Evolution of gene regulation has been proposed to play an important role in environmental adaptation. Exploring mechanisms underlying coordinated evolutionary changes at various levels of gene regulation could shed new light on how organism adapt in nature. In this study, we focused on regulatory differences between a laboratory Saccharomyces cerevisiae strain BY4742 and a pathogenic S. cerevisiae strain, YJM789. The two strains diverge in many features, including growth rate, morphology, high temperature tolerance, and pathogenicity. Our RNA-Seq and ribosomal footprint profiling data showed that gene expression differences are pervasive, and genes functioning in mitochondria are mostly divergent between the two strains at both transcriptional and translational levels. Combining functional genomics data from other yeast strains, we further demonstrated that significant divergence of expression for genes functioning in the electron transport chain (ETC was likely caused by differential expression of a transcriptional factor, HAP4, and that post-transcriptional regulation mediated by an RNA-binding protein, PUF3, likely led to expression divergence for genes involved in mitochondrial translation. We also explored mito-nuclear interactions via mitochondrial DNA replacement between strains. Although the two mitochondrial genomes harbor substantial sequence divergence, neither growth nor gene expression were affected by mitochondrial DNA replacement in both fermentative and respiratory growth media, indicating compatible mitochondrial and nuclear genomes between these two strains in the tested conditions. Collectively, we used mitochondrial functions as an example to demonstrate for the first time that evolution at both transcriptional and post-transcriptional levels could lead to coordinated regulatory changes underlying strain specific functional variations.

  7. Genetic evidence for the coordinated regulation of collagen fibrillogenesis in the cornea by decorin and biglycan.

    Science.gov (United States)

    Zhang, Guiyun; Chen, Shoujun; Goldoni, Silvia; Calder, Bennett W; Simpson, Holly C; Owens, Rick T; McQuillan, David J; Young, Marian F; Iozzo, Renato V; Birk, David E

    2009-03-27

    Decorin and biglycan are class I small leucine-rich proteoglycans (SLRPs) involved in regulation of collagen fibril and matrix assembly. We hypothesize that tissue-specific matrix assembly, such as in the cornea, requires a coordinate regulation involving multiple SLRPs. To this end, we investigated the expression of decorin and biglycan in the cornea of mice deficient in either SLRP gene and in double-mutant mice. Decorin and biglycan exhibited overlapping spatial expression patterns throughout the corneal stroma with differential temporal expression. Whereas decorin was expressed at relatively high levels in all developmental stages, biglycan expression was high early, decreased during development, and was present at very low levels in the mature cornea. Ultrastructural analyses demonstrated comparable fibril structure in the decorin- and biglycan-null corneas compared with wild-type controls. We found a compensatory up-regulation of biglycan gene expression in the decorin-deficient mice, but not the reverse. Notably, the corneas of compound decorin/biglycan-null mice showed severe disruption in fibril structure and organization, especially affecting the posterior corneal regions, corroborating the idea that biglycan compensates for the loss of decorin. Fibrillogenesis assays using recombinant decorin and biglycan confirmed a functional compensation, with both having similar effects at high SLRP/collagen ratios. However, at low ratios decorin was a more efficient regulator. The use of proteoglycan or protein core yielded comparable results. These findings provide firm genetic evidence for an interaction of decorin and biglycan during corneal development and further suggest that decorin has a primary role in regulating fibril assembly, a function that can be fine-tuned by biglycan during early development.

  8. Coordinated action of NSF and PKC regulates GABAB receptor signaling efficacy.

    Science.gov (United States)

    Pontier, Stéphanie M; Lahaie, Nicolas; Ginham, Rachel; St-Gelais, Fannie; Bonin, Hélène; Bell, David J; Flynn, Helen; Trudeau, Louis-Eric; McIlhinney, Jeffrey; White, Julia H; Bouvier, Michel

    2006-06-21

    The obligatory heterodimerization of the GABAB receptor (GBR) raises fundamental questions about molecular mechanisms controlling its signaling efficacy. Here, we show that NEM sensitive fusion (NSF) protein interacts directly with the GBR heterodimer both in rat brain synaptosomes and in CHO cells, forming a ternary complex that can be regulated by agonist stimulation. Inhibition of NSF binding with a peptide derived from GBR2 (TAT-Pep-27) did not affect basal signaling activity but almost completely abolished agonist-promoted GBR desensitization in both CHO cells and hippocampal slices. Taken with the role of PKC in the desensitization process, our observation that TAT-Pep-27 prevented both agonist-promoted recruitment of PKC and receptor phosphorylation suggests that NSF is a priming factor required for GBR desensitization. Given that GBR desensitization does not involve receptor internalization, the NSF/PKC coordinated action revealed herein suggests that NSF can regulate GPCR signalling efficacy independently of its role in membrane trafficking. The functional interaction between three bona fide regulators of neurotransmitter release, such as GBR, NSF and PKC, could shed new light on the modulation of presynaptic GBR action.

  9. Coordinated Regulation of Synaptic Plasticity at Striatopallidal and Striatonigral Neurons Orchestrates Motor Control

    Directory of Open Access Journals (Sweden)

    Massimo Trusel

    2015-11-01

    Full Text Available The basal ganglia play a critical role in shaping motor behavior. For this function, the activity of medium spiny neurons (MSNs of the striatonigral and striatopallidal pathways must be integrated. It remains unclear whether the activity of the two pathways is primarily coordinated by synaptic plasticity mechanisms. Using a model of Parkinson’s disease, we determined the circuit and behavioral effects of concurrently regulating cell-type-specific forms of corticostriatal long-term synaptic depression (LTD by inhibiting small-conductance Ca2+-activated K+ channels (SKs of the dorsolateral striatum. At striatopallidal synapses, SK channel inhibition rescued the disease-linked deficits in endocannabinoid (eCB-dependent LTD. At striatonigral cells, inhibition of these channels counteracted a form of adenosine-mediated LTD by activating the ERK cascade. Interfering with eCB-, adenosine-, and ERK signaling in vivo alleviated motor abnormalities, which supports that synaptic modulation of striatal pathways affects behavior. Thus, our results establish a central role of coordinated synaptic plasticity at MSN subpopulations in motor control.

  10. Voltage regulation in LV grids by coordinated volt-var control strategies

    DEFF Research Database (Denmark)

    Juamperez Goñi, Miguel Angel; Yang, Guangya; Kjær, Søren Bækhøj

    2014-01-01

    The increasing penetration level of photovoltaic (PV) power generation in low voltage (LV) networks results in voltage rise issues, particularly at the end of the feeders. In order to mitigate this problem, several strategies, such as grid reinforcement, transformer tap change, demand......-side management, active power curtailment, and reactive power optimization methods, show their contribution to voltage support, yet still limited. This paper proposes a coordinated volt-var control architecture between the LV distribution transformer and solar inverters to optimize the PV power penetration level...... in terms of network power losses and voltage level along the feeder. As a practical implementation, a reconfigurable hardware is used for developing a testing platform based on real-time measurements to regulate the reactive power level. The proposed testing platform has been developed within PVNET...

  11. Balancing Water Uptake and Loss through the Coordinated Regulation of Stomatal and Root Development

    Science.gov (United States)

    Hepworth, Christopher; Turner, Carla; Landim, Marcela Guimaraes; Cameron, Duncan; Gray, Julie E.

    2016-01-01

    Root development is influenced by nutrient and water availabilities. Plants are able to adjust many attributes of their root in response to environmental signals including the size and shape of the primary root, lateral roots and root hairs. Here we investigated the response of roots to changes in the levels of leaf transpiration associated with altered stomatal frequency. We found that plants with high stomatal density and conductance produce a larger rooting area and as a result have enhanced phosphate uptake capacity whereas plants with low stomatal conductance produce a smaller root. Manipulating the growth environment of plants indicated that enhanced root growth is most likely a result of an increased demand for water rather than phosphate. Plants manipulated to have an increase or reduction in root hair growth show a reduction or increase respectively, in stomatal conductance and density. Our results demonstrate that plants can balance their water uptake and loss through coordinated regulation of both stomatal and root development. PMID:27275842

  12. Interhemispheric claustral circuits coordinate somatomotor and visuomotor cortical areas that regulate exploratory behaviors

    Directory of Open Access Journals (Sweden)

    Jared Brent Smith

    2014-05-01

    Full Text Available The claustrum has a role in the interhemispheric transfer of certain types of sensorimotor information. Whereas the whisker region in rat motor (M1 cortex sends dense projections to the contralateral claustrum, the M1 forelimb representation does not. The claustrum sends strong ipsilateral projections to the whisker regions in M1 and somatosensory (S1 cortex, but its projections to the forelimb cortical areas are weak. These distinctions suggest that one function of the M1 projections to the contralateral claustrum is to coordinate the cortical areas that regulate peripheral sensor movements during behaviors that depend on bilateral sensory acquisition. If this hypothesis is true, then similar interhemispheric circuits should interconnect the frontal eye fields (FEF with the contralateral claustrum and its network of projections to vision-related cortical areas. To test this hypothesis, anterograde and retrograde tracers were placed in physiologically-defined parts of the FEF and primary visual cortex (V1 in rats. We observed dense FEF projections to the contralateral claustrum that terminated in the midst of claustral neurons that project to both FEF and V1. While the FEF inputs to the claustrum come predominantly from the contralateral hemisphere, the claustral projections to FEF and V1 are primarily ipsilateral. Detailed comparison of the present results with our previous studies on somatomotor claustral circuitry revealed a well-defined functional topography in which the ventral claustrum is connected with visuomotor cortical areas and the dorsal regions are connected with somatomotor areas. These results suggest that subregions within the claustrum play a critical role in coordinating the cortical areas that regulate the acquisition of modality-specific sensory information during exploration and other behaviors that require sensory attention.

  13. Gene expression profiling in wounded and systemic leaves of Fagus sylvatica reveals up-regulation of ethylene and jasmonic acid signalling.

    Science.gov (United States)

    Schlink, K

    2011-05-01

    Wounding is a crucial threat to plants because of the physical damage caused and the possible entry of pathogens. Little is known about the wound reaction in forest trees. Therefore, leaves of young beech trees were wounded and the transcriptional response of wounded leaves and leaves directly above and below was analysed. A total of 123 genes exhibited significant regulation. The magnitude of regulation was slightly weaker in the downward leaves but the regulation pattern resembles that of the local and upward reactions. Thus, the signal was transduced in both vertical directions. Genes exhibiting major regulation lacked functional assignment or belonged to signalling, transcription and defence categories. Signalling included activation of transcripts in the calcium and ethylene pathways. There was also evidence for activation of jasmonic acid signalling, but no activation of jasmonic acid-responsive PR (pathogenesis-related) genes was observed. Moreover, repression of salicylic acid responsive defence was measured. Metabolic changes included induction of a core gene of the phenylpropanoid pathway, while energy metabolism exhibited down-regulation. These results support the conclusion that young beech trees might give up leaves and/or reduce leaf energy content after an attack so as to deprive a putative herbivore of a nutrient supply, instead of investing much energy in leaf defence. © 2010 German Botanical Society and The Royal Botanical Society of the Netherlands.

  14. Notch down-regulation in regenerated epidermis contributes to enhanced expression of interleukin-36α and suppression of keratinocyte differentiation during wound healing.

    Science.gov (United States)

    Takazawa, Yuko; Ogawa, Eisaku; Saito, Rumiko; Uchiyama, Ryuhei; Ikawa, Shuntaro; Uhara, Hisashi; Okuyama, Ryuhei

    2015-07-01

    Notch signaling controls a number of cellular processes, including cell fate decisions, proliferation, differentiation, and survival/apoptosis, in multiple tissues. In the epidermis, Notch1 functions as a molecular switch that controls the transition of cells from an undifferentiated state into a differentiated state. To clarify the functions of Notch in the regenerated epidermis during wound healing. Wounds on mouse skin were immunostained. To investigate the functions of Notch, Notch was inhibited in primary keratinocytes by treatment with a γ-secretase inhibitor and by small interfering RNA-mediated knockdown, and was activated by a recombinant adenovirus approach. Notch1 and Notch2 were down-regulated in the regenerated epidermis during wound healing. To clarify the significance of this down-regulation, we examined its effect on expression of the interleukin (IL)-1 family of proinflammatory cytokines because wounds are exposed to pathogens from the outside world. Among the IL-1 family, IL-36α expression was induced by Notch inhibition. This was consistent with the decreased IL-36α expression in Notch-overexpressing keratinocytes. Notch down-regulation in the regenerated epidermis may reinforce defense against stress from the outside world by inducing IL-36α expression. Next, we examined the effects of Notch down-regulation on keratinocyte growth and differentiation. Notch down-regulation did not alter keratinocyte proliferation. On the other hand, Notch1 down-regulation suppressed induction of spinous layer-specific keratins (keratin1 and keratin10) in keratinocytes, which was consistent with the decreased expression of these keratins in the regenerated epidermis. The reduced levels of these keratins would increase cellular flexibility. Notch down-regulation in the epidermis appears to contribute to tissue regeneration during wound healing. Copyright © 2015 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights

  15. Bromelain down-regulates myofibroblast differentiation in an in vitro wound healing assay.

    Science.gov (United States)

    Aichele, Kathrin; Bubel, Monika; Deubel, Gunther; Pohlemann, Tim; Oberringer, Martin

    2013-10-01

    Bromelain, a pineapple-derived enzyme mixture, is a widely used drug to improve tissue regeneration. Clinical and experimental data indicate a better outcome of soft tissue healing under the influence of bromelain. Proteolytic, anti-bacterial, anti-inflammatory, and anti-oedematogenic effects account for this improvement on the systemic level. It remains unknown, whether involved tissue cells are directly influenced by bromelain. In order to gain more insight into those mechanisms by which bromelain modulates tissue regeneration at the cellular level, we applied a well-established in vitro wound healing assay. Two main players of soft tissue healing--fibroblasts and microvascular endothelial cells--were used as mono- and co-cultures. Cell migration, proliferation, apoptosis, and the differentiation of fibroblasts to myofibroblasts as well as interleukin-6 were quantified in response to bromelain (36 × 10(-3) IU/ml) under normoxia and hypoxia. Bromelain attenuated endothelial cell and fibroblast proliferation in a moderate way. This proliferation decrease was not caused by apoptosis, rather, by driving cells into the resting state G0 of the cell cycle. Endothelial cell migration was not influenced by bromelain, whereas fibroblast migration was clearly slowed down, especially under hypoxia. Bromelain led to a significant decrease of myofibroblasts under both normoxic (from 19 to 12 %) and hypoxic conditions (from 22 to 15 %), coincident with higher levels of interleukin-6. Myofibroblast differentiation, a clear sign of fibrotic development, can be attenuated by the application of bromelain in vitro. Usage of bromelain as a therapeutic drug for chronic human wounds thus remains a very promising concept for the future.

  16. Androgen Deprivation Accelerates the Prostatic Urethra Wound Healing After Thulium Laser Resection of the Prostate by Promoting Re-Epithelialization and Regulating the Macrophage Polarization.

    Science.gov (United States)

    Wang, Xing-Jie; Zhuo, Jian; Luo, Guang-Heng; Zhu, Yi-Ping; Yu, Dian-Jun; Zhao, Rui-Zhe; Jiang, Chen-Yi; Shi, Yun-Feng; Li, Hao; Chen, Lei; Hao, Kui-Yuan; Han, Xia; Zhao, Sheng; Bei, Xiao-Yu; Jing, Yi-Feng; Xia, Shu-Jie

    2017-05-01

    Complications after a thulium laser resection of the prostate (TmLRP) are related to re-epithelialization of the prostatic urethra. Since prostate growth and development are induced by androgen, the aim of this study was to determine the role and explore the mechanism of androgen in wound healing of the prostatic urethra. Beagles that received TmLRPs were randomly distributed into a castration group, a testosterone undecanoate (TU) group, and a control group. The prostate wound was assessed once a week using a cystoscope. Histological analysis was then carried out to study the re-epithelialization of the prostatic urethra in each group. The inflammatory response in the wound tissue and urine was also investigated. The healing of the prostatic urethra after a TmLRP was more rapid in the castration group and slower in the TU group than that in the control group. Castration accelerated re-epithelialization by promoting basal cell proliferation in the wound surface and beneath the wound and by accelerating the differentiation of basal cells into urothelial cells. Castration reduced the duration of the inflammatory phase and induced the conversion of M1 macrophages to M2 macrophages, thus accelerating the maturation of the wound. By contrast, androgen supplementation enhanced the inflammatory response and prolonged the inflammatory phase. Moreover, the anti-inflammatory phase was delayed and weakened. Androgen deprivation promotes re-epithelialization of the wound, regulates the inflammatory response, and accelerates wound healing of the prostatic urethra after a TmLRP. Prostate 77:708-717, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  17. Mea6 controls VLDL transport through the coordinated regulation of COPII assembly

    Science.gov (United States)

    Wang, Yaqing; Liu, Liang; Zhang, Hongsheng; Fan, Junwan; Zhang, Feng; Yu, Mei; Shi, Lei; Yang, Lin; Lam, Sin Man; Wang, Huimin; Chen, Xiaowei; Wang, Yingchun; Gao, Fei; Shui, Guanghou; Xu, Zhiheng

    2016-01-01

    Lipid accumulation, which may be caused by the disturbance in very low density lipoprotein (VLDL) secretion in the liver, can lead to fatty liver disease. VLDL is synthesized in endoplasmic reticulum (ER) and transported to Golgi apparatus for secretion into plasma. However, the underlying molecular mechanism for VLDL transport is still poorly understood. Here we show that hepatocyte-specific deletion of meningioma-expressed antigen 6 (Mea6)/cutaneous T cell lymphoma-associated antigen 5C (cTAGE5C) leads to severe fatty liver and hypolipemia in mice. Quantitative lipidomic and proteomic analyses indicate that Mea6/cTAGE5 deletion impairs the secretion of different types of lipids and proteins, including VLDL, from the liver. Moreover, we demonstrate that Mea6/cTAGE5 interacts with components of the ER coat protein complex II (COPII) which, when depleted, also cause lipid accumulation in hepatocytes. Our findings not only reveal several novel factors that regulate lipid transport, but also provide evidence that Mea6 plays a critical role in lipid transportation through the coordinated regulation of the COPII machinery. PMID:27311593

  18. Coordinate regulation of the mother centriole component nlp by nek2 and plk1 protein kinases.

    Science.gov (United States)

    Rapley, Joseph; Baxter, Joanne E; Blot, Joelle; Wattam, Samantha L; Casenghi, Martina; Meraldi, Patrick; Nigg, Erich A; Fry, Andrew M

    2005-02-01

    Mitotic entry requires a major reorganization of the microtubule cytoskeleton. Nlp, a centrosomal protein that binds gamma-tubulin, is a G(2)/M target of the Plk1 protein kinase. Here, we show that human Nlp and its Xenopus homologue, X-Nlp, are also phosphorylated by the cell cycle-regulated Nek2 kinase. X-Nlp is a 213-kDa mother centriole-specific protein, implicating it in microtubule anchoring. Although constant in abundance throughout the cell cycle, it is displaced from centrosomes upon mitotic entry. Overexpression of active Nek2 or Plk1 causes premature displacement of Nlp from interphase centrosomes. Active Nek2 is also capable of phosphorylating and displacing a mutant form of Nlp that lacks Plk1 phosphorylation sites. Importantly, kinase-inactive Nek2 interferes with Plk1-induced displacement of Nlp from interphase centrosomes and displacement of endogenous Nlp from mitotic spindle poles, while active Nek2 stimulates Plk1 phosphorylation of Nlp in vitro. Unlike Plk1, Nek2 does not prevent association of Nlp with gamma-tubulin. Together, these results provide the first example of a protein involved in microtubule organization that is coordinately regulated at the G(2)/M transition by two centrosomal kinases. We also propose that phosphorylation by Nek2 may prime Nlp for phosphorylation by Plk1.

  19. Synaptic microRNAs Coordinately Regulate Synaptic mRNAs: Perturbation by Chronic Alcohol Consumption.

    Science.gov (United States)

    Most, Dana; Leiter, Courtney; Blednov, Yuri A; Harris, R Adron; Mayfield, R Dayne

    2016-01-01

    Local translation of mRNAs in the synapse has a major role in synaptic structure and function. Chronic alcohol use causes persistent changes in synaptic mRNA expression, possibly mediated by microRNAs localized in the synapse. We profiled the transcriptome of synaptoneurosomes (SN) obtained from the amygdala of mice that consumed 20% ethanol (alcohol) in a 30-day continuous two-bottle choice test to identify the microRNAs that target alcohol-induced mRNAs. SN are membrane vesicles containing pre- and post-synaptic compartments of neurons and astroglia and are a unique model for studying the synaptic transcriptome. We previously showed that chronic alcohol regulates mRNA expression in a coordinated manner. Here, we examine microRNAs and mRNAs from the same samples to define alcohol-responsive synaptic microRNAs and their predicted interactions with targeted mRNAs. The aim of the study was to identify the microRNA-mRNA synaptic interactions that are altered by alcohol. This was accomplished by comparing the effect of alcohol in SN and total homogenate preparations from the same samples. We used a combination of unbiased bioinformatic methods (differential expression, correlation, co-expression, microRNA-mRNA target prediction, co-targeting, and cell type-specific analyses) to identify key alcohol-sensitive microRNAs. Prediction analysis showed that a subset of alcohol-responsive microRNAs was predicted to target many alcohol-responsive mRNAs, providing a bidirectional analysis for identifying microRNA-mRNA interactions. We found microRNAs and mRNAs with overlapping patterns of expression that correlated with alcohol consumption. Cell type-specific analysis revealed that a significant number of alcohol-responsive mRNAs and microRNAs were unique to glutamate neurons and were predicted to target each other. Chronic alcohol consumption appears to perturb the coordinated microRNA regulation of mRNAs in SN, a mechanism that may explain the aberrations in synaptic

  20. The Coordinated Positive Regulation of Topoisomerase Genes Maintains Topological Homeostasis in Streptomyces coelicolor.

    Science.gov (United States)

    Szafran, Marcin Jan; Gongerowska, Martyna; Gutkowski, Paweł; Zakrzewska-Czerwińska, Jolanta; Jakimowicz, Dagmara

    2016-11-01

    Maintaining an optimal level of chromosomal supercoiling is critical for the progression of DNA replication and transcription. Moreover, changes in global supercoiling affect the expression of a large number of genes and play a fundamental role in adapting to stress. Topoisomerase I (TopA) and gyrase are key players in the regulation of bacterial chromosomal topology through their respective abilities to relax and compact DNA. Soil bacteria such as Streptomyces species, which grow as branched, multigenomic hyphae, are subject to environmental stresses that are associated with changes in chromosomal topology. The topological fluctuations modulate the transcriptional activity of a large number of genes and in Streptomyces are related to the production of antibiotics. To better understand the regulation of topological homeostasis in Streptomyces coelicolor, we investigated the interplay between the activities of the topoisomerase-encoding genes topA and gyrBA We show that the expression of both genes is supercoiling sensitive. Remarkably, increased chromosomal supercoiling induces the topA promoter but only slightly influences gyrBA transcription, while DNA relaxation affects the topA promoter only marginally but strongly activates the gyrBA operon. Moreover, we showed that exposure to elevated temperatures induces rapid relaxation, which results in changes in the levels of both topoisomerases. We therefore propose a unique mechanism of S. coelicolor chromosomal topology maintenance based on the supercoiling-dependent stimulation, rather than repression, of the transcription of both topoisomerase genes. These findings provide important insight into the maintenance of topological homeostasis in an industrially important antibiotic producer. We describe the unique regulation of genes encoding two topoisomerases, topoisomerase I (TopA) and gyrase, in a model Streptomyces species. Our studies demonstrate the coordination of topoisomerase gene regulation, which is crucial

  1. The Aspergillus fumigatus Damage Resistance Protein Family Coordinately Regulates Ergosterol Biosynthesis and Azole Susceptibility

    Directory of Open Access Journals (Sweden)

    Jinxing Song

    2016-02-01

    Full Text Available Ergosterol is a major and specific component of the fungal plasma membrane, and thus, the cytochrome P450 enzymes (Erg proteins that catalyze ergosterol synthesis have been selected as valuable targets of azole antifungals. However, the opportunistic pathogen Aspergillus fumigatus has developed worldwide resistance to azoles largely through mutations in the cytochrome P450 enzyme Cyp51 (Erg11. In this study, we demonstrate that a cytochrome b5-like heme-binding damage resistance protein (Dap family, comprised of DapA, DapB, and DapC, coordinately regulates the functionality of cytochrome P450 enzymes Erg5 and Erg11 and oppositely affects susceptibility to azoles. The expression of all three genes is induced in an azole concentration-dependent way, and the decreased susceptibility to azoles requires DapA stabilization of cytochrome P450 protein activity. In contrast, overexpression of DapB and DapC causes dysfunction of Erg5 and Erg11, resulting in abnormal accumulation of sterol intermediates and further accentuating the sensitivity of ΔdapA strains to azoles. The results of exogenous-hemin rescue and heme-binding-site mutagenesis experiments demonstrate that the heme binding of DapA contributes the decreased azole susceptibility, while DapB and -C are capable of reducing the activities of Erg5 and Erg11 through depletion of heme. In vivo data demonstrate that inactivated DapA combined with activated DapB yields an A. fumigatus mutant that is easily treatable with azoles in an immunocompromised mouse model of invasive pulmonary aspergillosis. Compared to the single Dap proteins found in Saccharomyces cerevisiae and Schizosaccharomyces pombe, we suggest that this complex Dap family regulatory system emerged during the evolution of fungi as an adaptive means to regulate ergosterol synthesis in response to environmental stimuli.

  2. Coordinated Regulation of Vasopressin Inactivation and Glucose Uptake by Action of TUG Protein in Muscle.

    Science.gov (United States)

    Habtemichael, Estifanos N; Alcázar-Román, Abel; Rubin, Bradley R; Grossi, Laura R; Belman, Jonathan P; Julca, Omar; Löffler, Michael G; Li, Hongjie; Chi, Nai-Wen; Samuel, Varman T; Bogan, Jonathan S

    2015-06-05

    In adipose and muscle cells, insulin stimulates the exocytic translocation of vesicles containing GLUT4, a glucose transporter, and insulin-regulated aminopeptidase (IRAP), a transmembrane aminopeptidase. A substrate of IRAP is vasopressin, which controls water homeostasis. The physiological importance of IRAP translocation to inactivate vasopressin remains uncertain. We previously showed that in skeletal muscle, insulin stimulates proteolytic processing of the GLUT4 retention protein, TUG, to promote GLUT4 translocation and glucose uptake. Here we show that TUG proteolysis also controls IRAP targeting and regulates vasopressin action in vivo. Transgenic mice with constitutive TUG proteolysis in muscle consumed much more water than wild-type control mice. The transgenic mice lost more body weight during water restriction, and the abundance of renal AQP2 water channels was reduced, implying that vasopressin activity is decreased. To compensate for accelerated vasopressin degradation, vasopressin secretion was increased, as assessed by the cosecreted protein copeptin. IRAP abundance was increased in T-tubule fractions of fasting transgenic mice, when compared with controls. Recombinant IRAP bound to TUG, and this interaction was mapped to a short peptide in IRAP that was previously shown to be critical for GLUT4 intracellular retention. In cultured 3T3-L1 adipocytes, IRAP was present in TUG-bound membranes and was released by insulin stimulation. Together with previous results, these data support a model in which TUG controls vesicle translocation by interacting with IRAP as well as GLUT4. Furthermore, the effect of IRAP to reduce vasopressin activity is a physiologically important consequence of vesicle translocation, which is coordinated with the stimulation of glucose uptake. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Multiple structure-intrinsic disorder interactions regulate and coordinate Hox protein function

    Science.gov (United States)

    Bondos, Sarah

    During animal development, Hox transcription factors determine fate of developing tissues to generate diverse organs and appendages. Hox proteins are famous for their bizarre mutant phenotypes, such as replacing antennae with legs. Clearly, the functions of individual Hox proteins must be distinct and reliable in vivo, or the organism risks malformation or death. However, within the Hox protein family, the DNA-binding homeodomains are highly conserved and the amino acids that contact DNA are nearly invariant. These observations raise the question: How do different Hox proteins correctly identify their distinct target genes using a common DNA binding domain? One possible means to modulate DNA binding is through the influence of the non-homeodomain protein regions, which differ significantly among Hox proteins. However genetic approaches never detected intra-protein interactions, and early biochemical attempts were hindered because the special features of ``intrinsically disordered'' sequences were not appreciated. We propose the first-ever structural model of a Hox protein to explain how specific contacts between distant, intrinsically disordered regions of the protein and the homeodomain regulate DNA binding and coordinate this activity with other Hox molecular functions.

  4. Ascl1 Coordinately Regulates Gene Expression and the Chromatin Landscape during Neurogenesis

    Directory of Open Access Journals (Sweden)

    Alexandre A.S.F. Raposo

    2015-03-01

    Full Text Available The proneural transcription factor Ascl1 coordinates gene expression in both proliferating and differentiating progenitors along the neuronal lineage. Here, we used a cellular model of neurogenesis to investigate how Ascl1 interacts with the chromatin landscape to regulate gene expression when promoting neuronal differentiation. We find that Ascl1 binding occurs mostly at distal enhancers and is associated with activation of gene transcription. Surprisingly, the accessibility of Ascl1 to its binding sites in neural stem/progenitor cells remains largely unchanged throughout their differentiation, as Ascl1 targets regions of both readily accessible and closed chromatin in proliferating cells. Moreover, binding of Ascl1 often precedes an increase in chromatin accessibility and the appearance of new regions of open chromatin, associated with de novo gene expression during differentiation. Our results reveal a function of Ascl1 in promoting chromatin accessibility during neurogenesis, linking the chromatin landscape at Ascl1 target regions with the temporal progression of its transcriptional program.

  5. Balancing Water Uptake and Loss through the Coordinated Regulation of Stomatal and Root Development.

    Directory of Open Access Journals (Sweden)

    Christopher Hepworth

    Full Text Available Root development is influenced by nutrient and water availabilities. Plants are able to adjust many attributes of their root in response to environmental signals including the size and shape of the primary root, lateral roots and root hairs. Here we investigated the response of roots to changes in the levels of leaf transpiration associated with altered stomatal frequency. We found that plants with high stomatal density and conductance produce a larger rooting area and as a result have enhanced phosphate uptake capacity whereas plants with low stomatal conductance produce a smaller root. Manipulating the growth environment of plants indicated that enhanced root growth is most likely a result of an increased demand for water rather than phosphate. Plants manipulated to have an increase or reduction in root hair growth show a reduction or increase respectively, in stomatal conductance and density. Our results demonstrate that plants can balance their water uptake and loss through coordinated regulation of both stomatal and root development.

  6. The coordinating role of IQGAP1 in the regulation of local, endosome-specific actin networks

    Directory of Open Access Journals (Sweden)

    Edward B. Samson

    2017-06-01

    Full Text Available IQGAP1 is a large, multi-domain scaffold that helps orchestrate cell signaling and cytoskeletal mechanics by controlling interactions among a spectrum of receptors, signaling intermediates, and cytoskeletal proteins. While this coordination is known to impact cell morphology, motility, cell adhesion, and vesicular traffic, among other functions, the spatiotemporal properties and regulatory mechanisms of IQGAP1 have not been fully resolved. Herein, we describe a series of super-resolution and live-cell imaging analyses that identified a role for IQGAP1 in the regulation of an actin cytoskeletal shell surrounding a novel membranous compartment that localizes selectively to the basal cortex of polarized epithelial cells (MCF-10A. We also show that IQGAP1 appears to both stabilize the actin coating and constrain its growth. Loss of compartmental IQGAP1 initiates a disassembly mechanism involving rapid and unconstrained actin polymerization around the compartment and dispersal of its vesicle contents. Together, these findings suggest IQGAP1 achieves this control by harnessing both stabilizing and antagonistic interactions with actin. They also demonstrate the utility of these compartments for image-based investigations of the spatial and temporal dynamics of IQGAP1 within endosome-specific actin networks.

  7. The coordinating role of IQGAP1 in the regulation of local, endosome-specific actin networks.

    Science.gov (United States)

    Samson, Edward B; Tsao, David S; Zimak, Jan; McLaughlin, R Tyler; Trenton, Nicholaus J; Mace, Emily M; Orange, Jordan S; Schweikhard, Volker; Diehl, Michael R

    2017-06-15

    IQGAP1 is a large, multi-domain scaffold that helps orchestrate cell signaling and cytoskeletal mechanics by controlling interactions among a spectrum of receptors, signaling intermediates, and cytoskeletal proteins. While this coordination is known to impact cell morphology, motility, cell adhesion, and vesicular traffic, among other functions, the spatiotemporal properties and regulatory mechanisms of IQGAP1 have not been fully resolved. Herein, we describe a series of super-resolution and live-cell imaging analyses that identified a role for IQGAP1 in the regulation of an actin cytoskeletal shell surrounding a novel membranous compartment that localizes selectively to the basal cortex of polarized epithelial cells (MCF-10A). We also show that IQGAP1 appears to both stabilize the actin coating and constrain its growth. Loss of compartmental IQGAP1 initiates a disassembly mechanism involving rapid and unconstrained actin polymerization around the compartment and dispersal of its vesicle contents. Together, these findings suggest IQGAP1 achieves this control by harnessing both stabilizing and antagonistic interactions with actin. They also demonstrate the utility of these compartments for image-based investigations of the spatial and temporal dynamics of IQGAP1 within endosome-specific actin networks. © 2017. Published by The Company of Biologists Ltd.

  8. Aspergillus fumigatus allergen expression is coordinately regulated in response to hydrogen peroxide and cyclic AMP

    Directory of Open Access Journals (Sweden)

    Bowyer Paul

    2010-11-01

    Full Text Available Abstract Background A. fumigatus has been associated with a wide spectrum of allergic disorders such as ABPA or SAFS. It is poorly understood what allergens in particular are being expressed during fungal invasion and which are responsible for stimulation of immune responses. Study of the dynamics of allergen production by fungi may lead to insights into how allergens are presented to the immune system. Methods Expression of 17 A. fumigatus allergen genes was examined in response to various culture conditions and stimuli as well as in the presence of macrophages in order to mimic conditions encountered in the lung. Results Expression of 14/17 allergen genes was strongly induced by oxidative stress caused by hydrogen peroxide (Asp f 1, -2, -4, -5, -6, -7, -8, -10, -13, -17 and -18, all >10-fold and Asp f 11, -12, and -22, 5-10-fold and 16/17 allergen genes were repressed in the presence of cAMP. The 4 protease allergen genes (Asp f -5, -10, -13 and -18 were expressed at very low levels compared to the comparator (β-tubulin under all other conditions examined. Mild heat shock, anoxia, lipid and presence of macrophages did not result in coordinated changes in allergen gene expression. Growth on lipid as sole carbon source contributed to the moderate induction of most of the allergen genes. Heat shock (37°C > 42°C caused moderate repression in 11/17 genes (Asp f 1, -2, -4, -5, -6, -9, -10, -13, -17, -18 and -23 (2- to 9-fold, which was mostly evident for Asp f 1 and -9 (~9-fold. Anaerobic stress led to moderate induction of 13/17 genes (1.1 to 4-fold with one, Asp f 8 induced over 10-fold when grown under mineral oil. Complex changes were seen in gene expression during co-culture of A. fumigatus with macrophages. Conclusions Remarkable coordination of allergen gene expression in response to a specific condition (oxidative stress or the presence of cAMP has been observed, implying that a single biological stimulus may play a role in allergen gene

  9. Mechanical wounding induces a nitrosative stress by down-regulation of GSNO reductase and an increase in S-nitrosothiols in sunflower (Helianthus annuus) seedlings.

    Science.gov (United States)

    Chaki, Mounira; Valderrama, Raquel; Fernández-Ocaña, Ana M; Carreras, Alfonso; Gómez-Rodríguez, Maria V; Pedrajas, José R; Begara-Morales, Juan C; Sánchez-Calvo, Beatriz; Luque, Francisco; Leterrier, Marina; Corpas, Francisco J; Barroso, Juan B

    2011-03-01

    Nitric oxide (NO) and related molecules such as peroxynitrite, S-nitrosoglutathione (GSNO), and nitrotyrosine, among others, are involved in physiological processes as well in the mechanisms of response to stress conditions. In sunflower seedlings exposed to five different adverse environmental conditions (low temperature, mechanical wounding, high light intensity, continuous light, and continuous darkness), key components of the metabolism of reactive nitrogen species (RNS) and reactive oxygen species (ROS), including the enzyme activities L-arginine-dependent nitric oxide synthase (NOS), S-nitrosogluthathione reductase (GSNOR), nitrate reductase (NR), catalase, and superoxide dismutase, the content of lipid hydroperoxide, hydrogen peroxide, S-nitrosothiols (SNOs), the cellular level of NO, GSNO, and GSNOR, and protein tyrosine nitration [nitrotyrosine (NO(2)-Tyr)] were analysed. Among the stress conditions studied, mechanical wounding was the only one that caused a down-regulation of NOS and GSNOR activities, which in turn provoked an accumulation of SNOs. The analyses of the cellular content of NO, GSNO, GSNOR, and NO(2)-Tyr by confocal laser scanning microscopy confirmed these biochemical data. Therefore, it is proposed that mechanical wounding triggers the accumulation of SNOs, specifically GSNO, due to a down-regulation of GSNOR activity, while NO(2)-Tyr increases. Consequently a process of nitrosative stress is induced in sunflower seedlings and SNOs constitute a new wound signal in plants.

  10. Mechanical wounding induces a nitrosative stress by down-regulation of GSNO reductase and an increase in S-nitrosothiols in sunflower (Helianthus annuus) seedlings

    Science.gov (United States)

    Chaki, Mounira; Valderrama, Raquel; Fernández-Ocaña, Ana M.; Carreras, Alfonso; Gómez-Rodríguez, Maria. V.; Pedrajas, José R.; Begara-Morales, Juan C.; Sánchez-Calvo, Beatriz; Luque, Francisco; Leterrier, Marina; Corpas, Francisco J.; Barroso, Juan B.

    2011-01-01

    Nitric oxide (NO) and related molecules such as peroxynitrite, S-nitrosoglutathione (GSNO), and nitrotyrosine, among others, are involved in physiological processes as well in the mechanisms of response to stress conditions. In sunflower seedlings exposed to five different adverse environmental conditions (low temperature, mechanical wounding, high light intensity, continuous light, and continuous darkness), key components of the metabolism of reactive nitrogen species (RNS) and reactive oxygen species (ROS), including the enzyme activities L-arginine-dependent nitric oxide synthase (NOS), S-nitrosogluthathione reductase (GSNOR), nitrate reductase (NR), catalase, and superoxide dismutase, the content of lipid hydroperoxide, hydrogen peroxide, S-nitrosothiols (SNOs), the cellular level of NO, GSNO, and GSNOR, and protein tyrosine nitration [nitrotyrosine (NO2-Tyr)] were analysed. Among the stress conditions studied, mechanical wounding was the only one that caused a down-regulation of NOS and GSNOR activities, which in turn provoked an accumulation of SNOs. The analyses of the cellular content of NO, GSNO, GSNOR, and NO2-Tyr by confocal laser scanning microscopy confirmed these biochemical data. Therefore, it is proposed that mechanical wounding triggers the accumulation of SNOs, specifically GSNO, due to a down-regulation of GSNOR activity, while NO2-Tyr increases. Consequently a process of nitrosative stress is induced in sunflower seedlings and SNOs constitute a new wound signal in plants. PMID:21172815

  11. Simulation of Cell Group Formation Regulated by Coordination Number, Cell Cycle and Duplication Frequency

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    Shigehiro Hashimoto

    2013-08-01

    Full Text Available The effects of coordination number, a cell cycle and duplication frequency on cell-group formation have been investigated in a computer simulation. In the simulation, multiplication occurs in the last three steps of a cell cycle with a probability function to give variations in the interval. Each cell has a constant coordination number: four or six. When a cell gets surrounded by adjacent cells, its status changes from an active stage to a resting stage. Each cell repeats multiplication, and disappears when the times of multiplication reach to the limit. Variation was made in the coordination number, in the interval of multiplication and in the limited times of multiplication. The cells of the colony, which have the larger number of coordination, have reached the larger maximum population and disappeared earlier.

  12. Nitric Oxide Synthase Regulates Growth Coordination During Drosophila melanogaster Imaginal Disc Regeneration

    National Research Council Canada - National Science Library

    Jaszczak, Jacob S; Wolpe, Jacob B; Dao, Anh Q; Halme, Adrian

    2015-01-01

    .... Here we describe a pathway through which tissues communicate to coordinate growth. During Drosophila melanogaster larval development, damage to imaginal discs activates a regeneration checkpoint through expression of Dilp8...

  13. Wound care centers

    Science.gov (United States)

    ... wound care center; Diabetic ulcer - wound care center; Surgical wound - wound center; Ischemic ulcer - wound center ... types of non-healing wounds include: Pressure sores Surgical wounds Radiation sores Foot ulcers due to diabetes , poor ...

  14. The role of histamine in the regulation of the viability, proliferation and transforming growth factor β1 secretion of rat wound fibroblasts.

    Science.gov (United States)

    Wolak, Monika; Bojanowska, Ewa; Staszewska, Teresa; Ciosek, Joanna; Juszczak, Marlena; Drobnik, Jacek

    2017-04-01

    Inflammation mediators play a regulatory role in repair processes. The study will examine the influence of histamine on wound fibroblast metabolic activity, viability, proliferation, and TGFβ1 secretion. The study also will identify the histamine receptor involved in regulation of the tested repair processes. Fibroblasts were obtained from the granulation tissue of wounds or intact dermis of rats. The MTT and BrdU assays were used to examine the effect of histamine (10-8M-10-4M) on the viability and metabolic activity of fibroblasts, and on their proliferative capacity. The influence of histamine receptor antagonists (i.e., ketotifen, ranitidine, ciproxifan and JNJ7777120) and agonists (2-pyridylethlamine dihydrochloride, amthamine dihydrobromide) was also investigated. The TGFβ1 and histamine receptors H1 were evaluated by enzyme-linked immunosorbent assay. Histamine significantly increased granulation tissue fibroblast viability and metabolic activity at 10-8 and 10-6M but did not change their proliferative activity. Only the blockade of the H1 receptor removed this effect of histamine. H1 receptor agonist (2-pyridylethlamine dihydrochloride) increased cell viability, thereby mimicking histamine action. Both Histamine (10-4M) and 2-pyridylethlamine dihydrochloride increased TGFβ1 concentration in cell culture medium. However, ketotifen blocked histamine-induced augmentation of TGFβ1. H1 receptor expression on wound fibroblasts was confirmed. The regulatory influence of histamine on wound fibroblast function (viability/metabolic activity or secretion of TGFβ1) is dependent on H1 receptor stimulation. Contrary to wound fibroblasts, these cells express a very low level of H1 receptors when isolated from intact dermis and histamine is unable to modify their metabolic activity. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

  15. Puncture Wounds

    Science.gov (United States)

    ... particles of which can get trapped in the wound. Treatment A puncture wound must be cleaned properly and ... play a crucial role in preventing them. Puncture Wounds: What You Should Do Seek treatment right away. Get a tetanus shot if needed ( ...

  16. Cerebellar Shank2 Regulates Excitatory Synapse Density, Motor Coordination, and Specific Repetitive and Anxiety-Like Behaviors.

    Science.gov (United States)

    Ha, Seungmin; Lee, Dongwon; Cho, Yi Sul; Chung, Changuk; Yoo, Ye-Eun; Kim, Jihye; Lee, Jiseok; Kim, Woohyun; Kim, Hyosang; Bae, Yong Chul; Tanaka-Yamamoto, Keiko; Kim, Eunjoon

    2016-11-30

    Shank2 is a multidomain scaffolding protein implicated in the structural and functional coordination of multiprotein complexes at excitatory postsynaptic sites as well as in psychiatric disorders, including autism spectrum disorders. While Shank2 is strongly expressed in the cerebellum, whether Shank2 regulates cerebellar excitatory synapses, or contributes to the behavioral abnormalities observed in Shank2-/- mice, remains unexplored. Here we show that Shank2-/- mice show reduced excitatory synapse density in cerebellar Purkinje cells in association with reduced levels of excitatory postsynaptic proteins, including GluD2 and PSD-93, and impaired motor coordination in the Erasmus test. Shank2 deletion restricted to Purkinje cells (Pcp2-Cre;Shank2fl/fl mice) leads to similar reductions in excitatory synapse density, synaptic protein levels, and motor coordination. Pcp2-Cre;Shank2fl/fl mice do not recapitulate autistic-like behaviors observed in Shank2-/- mice, such as social interaction deficits, altered ultrasonic vocalizations, repetitive behaviors, and hyperactivity. However, Pcp2-Cre;Shank2fl/fl mice display enhanced repetitive behavior in the hole-board test and anxiety-like behavior in the light-dark test, which are not observed in Shank2-/- mice. These results implicate Shank2 in the regulation of cerebellar excitatory synapse density, motor coordination, and specific repetitive and anxiety-like behaviors. The postsynaptic side of excitatory synapses contains multiprotein complexes, termed the postsynaptic density, which contains receptors, scaffolding/adaptor proteins, and signaling molecules. Shank2 is an excitatory postsynaptic scaffolding protein implicated in the formation and functional coordination of the postsynaptic density and has been linked to autism spectrum disorders. Using Shank2-null mice and Shank2-conditional knock-out mice with a gene deletion restricted to cerebellar Purkinje cells, we explored functions of Shank2 in the cerebellum. We

  17. DNA Damage-Inducible Transcript 4 Is an Innate Surveillant of Hair Follicular Stress in Vitamin D Receptor Knockout Mice and a Regulator of Wound Re-Epithelialization

    Directory of Open Access Journals (Sweden)

    Hengguang Zhao

    2016-11-01

    Full Text Available Mice and human patients with impaired vitamin D receptor (VDR signaling have normal developmental hair growth but display aberrant post-morphogenic hair cycle progression associated with alopecia. In addition, VDR–/– mice exhibit impaired cutaneous wound healing. We undertook experiments to determine whether the stress-inducible regulator of energy homeostasis, DNA damage-inducible transcript 4 (Ddit4, is involved in these processes. By analyzing hair cycle activation in vivo, we show that VDR−/− mice at day 14 exhibit increased Ddit4 expression within follicular stress compartments. At day 29, degenerating VDR−/− follicular keratinocytes, but not bulge stem cells, continue to exhibit an increase in Ddit4 expression. At day 47, when normal follicles and epidermis are quiescent and enriched for Ddit4, VDR−/− skin lacks Ddit4 expression. In a skin wound healing assay, the re-epithelialized epidermis in wildtype (WT but not VDR−/− animals harbor a population of Ddit4- and Krt10-positive cells. Our study suggests that VDR regulates Ddit4 expression during epidermal homeostasis and the wound healing process, while elevated Ddit4 represents an early growth-arresting stress response within VDR−/− follicles.

  18. Short term supplementation of dietary antioxidants selectively regulates the inflammatory responses during early cutaneous wound healing in diabetic mice

    Directory of Open Access Journals (Sweden)

    Park Na-Young

    2011-11-01

    Full Text Available Abstract Background Diabetic foot ulcers are serious complications for diabetic patients, yet the precise mechanism that underlines the treatment of these diabetic complications remains unclear. We hypothesized that dietary antioxidant supplementation with vitamin C, combined either with vitamin E or with vitamin E and NAC, improves delayed wound healing through modulation of blood glucose levels, oxidative stress, and inflammatory response. Methods Diabetes was induced by administration of alloxan monohydrate. Mice were divided into 4 groups; CON (non-diabetic control mice fed AIN 93 G purified rodent diet, DM (diabetic mice fed AIN 93 G purified rodent diet, VCE (diabetic mice fed 0.5% vitamin C and 0.5% vitamin E supplemented diet, and Comb (diabetic mice fed 0.5% vitamin C, 0.5% vitamin E, and 2.5% NAC supplemented diet. After 10 days of dietary antioxidant supplementation, cutaneous full-thickness excisional wounds were performed, and the rate of wound closure was examined. TBARS as lipid peroxidation products and vitamin E levels were measured in the liver. Expression levels of oxidative stress and inflammatory response related proteins were measured in the cutaneous wound site. Results Dietary antioxidant supplementation improved blood glucose levels and wound closure rate and increased liver vitamin E, but not liver TBARS levels in the diabetic mice as compared to those of the CON. In addition, dietary antioxidant supplementation modulated the expression levels of pIκBα, HO-1, CuZnSOD, iNOS and COX-2 proteins in the diabetic mice. Conclusions These findings demonstrated that delayed wound healing is associated with an inflammatory response induced by hyperglycaemia, and suggests that dietary antioxidant supplementation may have beneficial effects on wound healing through selective modulation of blood glucose levels, oxidative stress, and inflammatory response.

  19. Hearts and minds: Coordination of neurocognitive and cardiovascular regulation in children and adolescents

    NARCIS (Netherlands)

    Chapman, H.A.; Woltering, S.; Lamm, C.; Lewis, M.D.

    2010-01-01

    Emotional reactions involve changes in both cognitive and bodily processes. Therefore, effective emotion regulation may also involve modulation of responses in both of these systems. The present study investigated the relationship between regulation of cognition and regulation of the heart in

  20. Silibinin regulates matrix metalloproteinase 3 (stromelysine1) gene expression, hexoseamines and collagen production during rat skin wound healing.

    Science.gov (United States)

    Tabandeh, Mohammad Reza; Oryan, Ahamd; Mohhammad-Alipour, Adel; Tabatabaei-Naieni, Abotorab

    2013-08-01

    Silibinin (SB), a flavonoid isolated from the milk thistle, Silybum marianum, has been shown to exhibit protective effects against skin damage. The objective of the present study was to investigate the effect of topical application of SB on levels of stromelysine 1 (STM1) gene expression, acetyl hexoseamines and collagen production during skin wound healing. Full-thickness skin wounds were topically treated with 10% and 20% SB extract in acetonitril:olive oil (AOO) (4:1) for 30 days, and expression level of STM1 transcript, n-acetyl glucoseamine (NAGLA), n-acetyl galactoseamine (NAGAA) and collagen contents were analyzed on the 10th, 20th and 30th days post wounding. SB in dose- and time-dependent manner accelerated wound closure time and increased levels of STM1 mRNA, hydroxyproline, NAGLA and NAGAA compared to the untreated and vehicle (AOO)-treated rats. The current study provides evidence that SB, by increasing STM1 gene expression and extracellular matrix constituents including glycosaminoglycans and collagen contents, promotes a faster wound healing process and can be used as a healing agent in future. Copyright © 2012 John Wiley & Sons, Ltd.

  1. Coordinating cell proliferation and differentiation: Antagonism between cell cycle regulators and cell type-specific gene expression

    Science.gov (United States)

    Ruijtenberg, Suzan; van den Heuvel, Sander

    2016-01-01

    ABSTRACT Cell proliferation and differentiation show a remarkable inverse relationship. Precursor cells continue division before acquiring a fully differentiated state, while terminal differentiation usually coincides with proliferation arrest and permanent exit from the division cycle. Mechanistic insight in the temporal coordination between cell cycle exit and differentiation has come from studies of cells in culture and genetic animal models. As initially described for skeletal muscle differentiation, temporal coordination involves mutual antagonism between cyclin-dependent kinases that promote cell cycle entry and transcription factors that induce tissue-specific gene expression. Recent insights highlight the contribution of chromatin-regulating complexes that act in conjunction with the transcription factors and determine their activity. In particular SWI/SNF chromatin remodelers contribute to dual regulation of cell cycle and tissue-specific gene expression during terminal differentiation. We review the concerted regulation of the cell cycle and cell type-specific transcription, and discuss common mutations in human cancer that emphasize the clinical importance of proliferation versus differentiation control. PMID:26825227

  2. Coordinated regulation of niche and stem cell precursors by hormonal signaling.

    Directory of Open Access Journals (Sweden)

    Dana Gancz

    2011-11-01

    Full Text Available Stem cells and their niches constitute units that act cooperatively to achieve adult body homeostasis. How such units form and whether stem cell and niche precursors might be coordinated already during organogenesis are unknown. In fruit flies, primordial germ cells (PGCs, the precursors of germ line stem cells (GSCs, and somatic niche precursors develop within the larval ovary. Together they form the 16-20 GSC units of the adult ovary. We show that ecdysone receptors are required to coordinate the development of niche and GSC precursors. At early third instar, ecdysone receptors repress precocious differentiation of both niches and PGCs. Early repression is required for correct morphogenesis of the ovary and for protecting future GSCs from differentiation. At mid-third instar, ecdysone signaling is required for niche formation. Finally, and concurrent with the initiation of wandering behavior, ecdysone signaling initiates PGC differentiation by allowing the expression of the differentiation gene bag of marbles in PGCs that are not protected by the newly formed niches. All the ovarian functions of ecdysone receptors are mediated through early repression, and late activation, of the ecdysone target gene broad. These results show that, similar to mammals, a brain-gland-gonad axis controls the initiation of oogenesis in insects. They further exemplify how a physiological cue coordinates the formation of a stem cell unit within an organ: it is required for niche establishment and to ensure that precursor cells to adult stem cells remain undifferentiated until the niches can accommodate them. Similar principles might govern the formation of additional stem cell units during organogenesis.

  3. Multiple diguanylate cyclase-coordinated regulation of pyoverdine synthesis in Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Chen, Yicai; Yuan, Mingjun; Mohanty, Anee

    2015-01-01

    of exopolysaccharides and another two DGCs, SiaD and SadC. SiaD was found to boost the c-di-GMP synthesis together with constitutively expressing YedQ. The exopolysaccharides and the SiaD DGC were found to modulate the expression of the RsmY/RsmZ ncRNAs. Induction of the RsmY/RsmZ ncRNAs might enhance the pyoverdine...... synthesis through SadC. Our study sheds light on a novel multiple DGC-coordinated c-di-GMP regulatory mechanism of bacteria....

  4. Vibrational spectra and normal coordinate analysis of plant growth regulator 1-naphthalene acetamide

    Science.gov (United States)

    Ravikumar, C.; Padmaja, L.; Hubert Joe, I.

    2010-02-01

    FT Raman and IR spectra of the biologically active molecule, 1-naphthalene acetamide (NA) have been recorded and analyzed. The equilibrium geometry, bonding features and harmonic vibrational wavenumbers of NA have been calculated with the help of B3LYP density functional theory (DFT) method. The assignments of the vibrational spectra have been carried out with the help of normal coordinate analysis (NCA) following the scaled quantum mechanical force field methodology (SQMFF). The downshifting of NH 2 stretching wavenumber indicates the formation of intermolecular N-H⋯O hydrogen bonding. The NBO analysis confirms the occurrence of strong intermolecular hydrogen bonding in the molecule.

  5. Wounding induces changes in cytokinin and auxin content in potato tuber, but does not induce formation of gibberellins.

    Science.gov (United States)

    Lulai, Edward C; Suttle, Jeffrey C; Olson, Linda L; Neubauer, Jonathan D; Campbell, Larry G; Campbell, Michael A

    2016-02-01

    Cytokinin, auxin and gibberellin contents in resting and wound-responding potato tubers have not been fully determined and coordinated with wound-healing processes. Using a well-defined wound-healing model system, hormone content and expression of genes associated with hormone turnover were determined in tubers following wounding. Changes in hormone content were coordinated with: (I) formation and completion of the wound closing layer (0-5/6 days), and (II) initiation of phellogen and wound periderm formation (∼ 7 days). Quantifiable amounts of biologically active cytokinins (Z, DZ and IP) were not detected in resting or wound-responding tubers. However, the precursor IPA and catabolic product c-ZOG were found in small amounts in resting and wound-responding tubers. Wound-induced activation of cytokinin biosynthesis was suggested by an increase in t-ZR and c-ZR content at 0.5 days and large increases in IPA and c-ZR content by 3 days and throughout 7 days after wounding suggesting roles in II, but little or no role in I. Expression of key genes involved in cytokinin metabolism followed similar profiles with transcripts decreasing through 3 days and then increasing at 5-7 days after wounding. Both free IAA and IAA-Asp were present in resting tubers. While IAA-Asp was no longer present by 3 days after wounding, IAA content nearly doubled by 5 days and was more than 4-fold greater at 7 days compared to that in resting tuber (0 day) suggesting roles in II, but little or no role in I. Gibberellins were not present in quantifiable amounts in resting or wound-responding tubers. These results suggest that bio-active cytokinins are wound-induced, but their residency is temporal and highly regulated. The transient presence of active cytokinins and corresponding increases in IAA content strongly suggest their involvement in the regulation of wound periderm development. The absence of gibberellins indicates that they are not a regulatory component of wound-healing processes

  6. Metabolic regulation is sufficient for global and robust coordination of glucose uptake, catabolism, energy production and growth in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Pierre Millard

    2017-02-01

    Full Text Available The metabolism of microorganisms is regulated through two main mechanisms: changes of enzyme capacities as a consequence of gene expression modulation ("hierarchical control" and changes of enzyme activities through metabolite-enzyme interactions. An increasing body of evidence indicates that hierarchical control is insufficient to explain metabolic behaviors, but the system-wide impact of metabolic regulation remains largely uncharacterized. To clarify its role, we developed and validated a detailed kinetic model of Escherichia coli central metabolism that links growth to environment. Metabolic control analyses confirm that the control is widely distributed across the network and highlight strong interconnections between all the pathways. Exploration of the model solution space reveals that several robust properties emerge from metabolic regulation, from the molecular level (e.g. homeostasis of total metabolite pool to the overall cellular physiology (e.g. coordination of carbon uptake, catabolism, energy and redox production, and growth, while allowing a large degree of flexibility at most individual metabolic steps. These properties have important physiological implications for E. coli and significantly expand the self-regulating capacities of its metabolism.

  7. Proteomic Analysis Reveals Coordinated Regulation of Anthocyanin Biosynthesis through Signal Transduction and Sugar Metabolism in Black Rice Leaf

    Directory of Open Access Journals (Sweden)

    Linghua Chen

    2017-12-01

    Full Text Available Black rice (Oryza sativa L. is considered to be a healthy food due to its high content of anthocyanins in the pericarp. The synthetic pathway of anthocyanins in black rice grains has been identified, however, the proteomic profile of leaves during grain development is still unclear. Here, isobaric Tags Relative and Absolute Quantification (iTRAQ MS/MS was carried out to identify statistically significant changes of leaf proteome in the black rice during grain development. Throughout three sequential developmental stages, a total of 3562 proteins were detected and 24 functional proteins were differentially expressed 3–10 days after flowering (DAF. The detected proteins are known to be involved in various biological processes and most of these proteins were related to gene expression regulatory (33.3%, signal transduction (16.7% and developmental regulation and hormone-like proteins (12.5%. The coordinated changes were consistent with changes in regulatory proteins playing a leading role in leaves during black rice grain development. This indicated that signal transduction between leaves and grains may have an important role in anthocyanin biosynthesis and accumulation during grain development of black rice. In addition, four identified up-regulated proteins associated with starch metabolism suggested that the remobilization of nutrients for starch synthesis plays a potential role in anthocyanin biosynthesis of grain. The mRNA transcription for eight selected proteins was validated with quantitative real-time PCR. Our results explored the proteomics of the coordination between leaf and grain in anthocyanins biosynthesis of grain, which might be regulated by signal transduction and sugar metabolism in black rice leaf.

  8. Multiple Mechanisms Drive Calcium Signal Dynamics around Laser-Induced Epithelial Wounds.

    Science.gov (United States)

    Shannon, Erica K; Stevens, Aaron; Edrington, Westin; Zhao, Yunhua; Jayasinghe, Aroshan K; Page-McCaw, Andrea; Hutson, M Shane

    2017-10-03

    Epithelial wound healing is an evolutionarily conserved process that requires coordination across a field of cells. Studies in many organisms have shown that cytosolic calcium levels rise within a field of cells around the wound and spread to neighboring cells, within seconds of wounding. Although calcium is a known potent second messenger and master regulator of wound-healing programs, it is unknown what initiates the rise of cytosolic calcium across the wound field. Here we use laser ablation, a commonly used technique for the precision removal of cells or subcellular components, as a tool to investigate mechanisms of calcium entry upon wounding. Despite its precise ablation capabilities, we find that this technique damages cells outside the primary wound via a laser-induced cavitation bubble, which forms and collapses within microseconds of ablation. This cavitation bubble damages the plasma membranes of cells it contacts, tens of microns away from the wound, allowing direct calcium entry from extracellular fluid into damaged cells. Approximately 45 s after this rapid influx of calcium, we observe a second influx of calcium that spreads to neighboring cells beyond the footprint of cavitation. The occurrence of this second, delayed calcium expansion event is predicted by wound size, indicating that a separate mechanism of calcium entry exists, corresponding to cell loss at the primary wound. Our research demonstrates that the damage profile of laser ablation is more similar to a crush injury than the precision removal of individual cells. The generation of membrane microtears upon ablation is consistent with studies in the field of optoporation, which investigate ablation-induced cellular permeability. We conclude that multiple types of damage, including microtears and cell loss, result in multiple mechanisms of calcium influx around epithelial wounds. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  9. Coordinated action of NSF and PKC regulates GABAB receptor signaling efficacy

    OpenAIRE

    Pontier, Stéphanie M; Lahaie, Nicolas; Ginham, Rachel; St-Gelais, Fannie; Bonin, Hélène; Bell, David J; Flynn, Helen; Trudeau, Louis-Eric; McIlhinney, Jeffrey; White, Julia H; Bouvier, Michel

    2006-01-01

    The obligatory heterodimerization of the GABAB receptor (GBR) raises fundamental questions about molecular mechanisms controlling its signaling efficacy. Here, we show that NEM sensitive fusion (NSF) protein interacts directly with the GBR heterodimer both in rat brain synaptosomes and in CHO cells, forming a ternary complex that can be regulated by agonist stimulation. Inhibition of NSF binding with a peptide derived from GBR2 (TAT-Pep-27) did not affect basal signaling activity but almost c...

  10. Regional monitoring of capital flows and coordination of financial regulation: Stakes and options for Asia

    OpenAIRE

    Plummer, Michael G.

    2010-01-01

    The ongoing global economic crisis has punished Asian economies severely, despite the fact that its origins derive from outside the region. The global economic crisis was transmitted through real and financial channels, underscoring how vulnerable the region is to external shocks. This paper explores the microeconomic origins of the financial crisis and endeavors to ascertain how crises might be mitigated in the future through better regulation, supervision, and institution-building. Moreover...

  11. Hypothalamic Y2 Receptors: Central Coordination of Energy Homeostasis and Bone Mass Regulation.

    Science.gov (United States)

    Herzog, Herbert

    2002-10-01

    Neuropeptide Y (NPY) in the central nervous system is a major regulator of food consumption and energy homeostasis. It also regulates blood pressure, induces anxiolysis, enhances memory retention and affects circadian rhythms, as well as modulates hormone release. Five Y receptors are known that mediate the action of NPY and its two other family members, peptide YY and pancreatic polypeptide. Increased NPY signaling due to elevated NPY expression in the hypothalamus leads to the development of obesity and its related phenotypes, type 2 diabetes and cardiovascular disease. Dysregulation in NPY signaling also causes alterations in bone formation. The large number of Y receptors has made it difficult to delineate their individual contributions to these physiological processes. However, recent studies analyzing Y-receptor knockout models have started to unravel some of the individual functions of these Y receptors. Particularly, the use of conditional knockout models has made it possible to pinpoint a specific functional contribution to an individual Y receptor in a particular location. From these studies, the predominantly presynaptically expressed Y2 receptor in the arcuate nucleus of the hypothalamus has emerged as a prime candidate for mediating satiety as well as a candidate for regulating bone formation. (c) 2002 Prous Science. All rights reserved.

  12. Coordinated Regulations of mRNA Synthesis and Decay during Cold Acclimation in Arabidopsis Cells.

    KAUST Repository

    Arae, Toshihiro

    2017-04-18

    Plants possess a cold acclimation system to acquire freezing tolerance through pre-exposure to non-freezing low temperatures. The transcriptional cascade of C-repeat binding factors (CBFs)/dehydration response element-binding factors (DREBs) is considered a major transcriptional regulatory pathway during cold acclimation. However, little is known regarding the functional significance of mRNA stability regulation in the response of gene expression to cold stress. The actual level of individual mRNAs is determined by a balance between mRNA synthesis and degradation. Therefore, it is important to assess the regulatory steps to increase our understanding of gene regulation. Here, we analyzed temporal changes in mRNA amounts and half-lives in response to cold stress in Arabidopsis cell cultures based on genome-wide analysis. In this mRNA decay array method, mRNA half-life measurements and microarray analyses were combined. In addition, temporal changes in the integrated value of transcription rates were estimated from the above two parameters using a mathematical approach. Our results showed that several cold-responsive genes, including Cold-regulated 15a, were relatively destabilized, whereas the mRNA amounts were increased during cold treatment by accelerating the transcription rate to overcome the destabilization. Considering the kinetics of mRNA synthesis and degradation, this apparently contradictory result supports that mRNA destabilization is advantageous for the swift increase in CBF-responsive genes in response to cold stress.

  13. Image acquisition and planimetry systems to develop wounding techniques in 3D wound model

    Directory of Open Access Journals (Sweden)

    Kiefer Ann-Kathrin

    2017-09-01

    Full Text Available Wound healing represents a complex biological repair process. Established 2D monolayers and wounding techniques investigate cell migration, but do not represent coordinated multi-cellular systems. We aim to use wound surface area measurements obtained from image acquisition and planimetry systems to establish our wounding technique and in vitro organotypic tissue. These systems will be used in our future wound healing treatment studies to assess the rate of wound closure in response to wound healing treatment with light therapy (photobiomodulation. The image acquisition and planimetry systems were developed, calibrated, and verified to measure wound surface area in vitro. The system consists of a recording system (Sony DSC HX60, 20.4 M Pixel, 1/2.3″ CMOS sensor and calibrated with 1mm scale paper. Macro photography with an optical zoom magnification of 2:1 achieves sufficient resolution to evaluate the 3mm wound size and healing growth. The camera system was leveled with an aluminum construction to ensure constant distance and orientation of the images. The JPG-format images were processed with a planimetry system in MATLAB. Edge detection enables definition of the wounded area. Wound area can be calculated with surface integrals. To separate the wounded area from the background, the image was filtered in several steps. Agar models, injured through several test persons with different levels of experience, were used as pilot data to test the planimetry software. These image acquisition and planimetry systems support the development of our wound healing research. The reproducibility of our wounding technique can be assessed by the variability in initial wound surface area. Also, wound healing treatment effects can be assessed by the change in rate of wound closure. These techniques represent the foundations of our wound model, wounding technique, and analysis systems in our ongoing studies in wound healing and therapy.

  14. The circadian protein period 1 contributes to blood pressure control and coordinately regulates renal sodium transport genes.

    Science.gov (United States)

    Stow, Lisa R; Richards, Jacob; Cheng, Kit-Yan; Lynch, I Jeanette; Jeffers, Lauren A; Greenlee, Megan M; Cain, Brian D; Wingo, Charles S; Gumz, Michelle L

    2012-06-01

    The circadian clock protein period 1 (Per1) contributes to the regulation of expression of the α subunit of the renal epithelial sodium channel at the basal level and in response to the mineralocorticoid hormone aldosterone. The goals of the present study were to define the role of Per1 in the regulation of additional renal sodium handling genes in cortical collecting duct cells and to evaluate blood pressure (BP) in mice lacking functional Per1. To determine whether Per1 regulates additional genes important in renal sodium handling, a candidate gene approach was used. Immortalized collecting duct cells were transfected with a nontarget small interfering RNA or a Per1-specific small interfering RNA. Expression of the genes for α-epithelial sodium channel and Fxyd5, a positive regulator of Na, K-ATPase activity, decreased in response to Per1 knockdown. Conversely, mRNA expression of caveolin 1, Ube2e3, and ET-1, all negative effectors of epithelial sodium channel, was induced after Per1 knockdown. These results led us to evaluate BP in Per1 KO mice. Mice lacking Per1 exhibit significantly reduced BP and elevated renal ET-1 levels compared with wild-type animals. Given the established role of renal ET-1 in epithelial sodium channel inhibition and BP control, elevated renal ET-1 is one possible explanation for the lower BP observed in Per1 KO mice. These data support a role for the circadian clock protein Per1 in the coordinate regulation of genes involved in renal sodium reabsorption. Importantly, the lower BP observed in Per1 KO mice compared with wild-type mice suggests a role for Per1 in BP control as well.

  15. c-Myb Regulates the T-Bet-Dependent Differentiation Program in B Cells to Coordinate Antibody Responses

    Directory of Open Access Journals (Sweden)

    Dana Piovesan

    2017-04-01

    Full Text Available Humoral immune responses are tailored to the invading pathogen through regulation of key transcription factors and their networks. This is critical to establishing effective antibody-mediated responses, yet it is unknown how B cells integrate pathogen-induced signals to drive or suppress transcriptional programs specialized for each class of pathogen. Here, we detail the key role of the transcription factor c-Myb in regulating the T-bet-mediated anti-viral program. Deletion of c-Myb in mature B cells significantly increased serum IgG2c and CXCR3 expression by upregulating T-bet, normally suppressed during Th2-cell-mediated responses. Enhanced expression of T-bet resulted in aberrant plasma cell differentiation within the germinal center, mediated by CXCR3 expression. These findings identify a dual role for c-Myb in limiting inappropriate effector responses while coordinating plasma cell differentiation with germinal center egress. Identifying such intrinsic regulators of specialized antibody responses can assist in vaccine design and therapeutic intervention in B-cell-mediated immune disorders.

  16. c-Myb Regulates the T-Bet-Dependent Differentiation Program in B Cells to Coordinate Antibody Responses.

    Science.gov (United States)

    Piovesan, Dana; Tempany, Jessica; Di Pietro, Andrea; Baas, Inge; Yiannis, Callisthenis; O'Donnell, Kristy; Chen, Yunshun; Peperzak, Victor; Belz, Gabrielle T; Mackay, Charles R; Smyth, Gordon K; Groom, Joanna R; Tarlinton, David M; Good-Jacobson, Kim L

    2017-04-18

    Humoral immune responses are tailored to the invading pathogen through regulation of key transcription factors and their networks. This is critical to establishing effective antibody-mediated responses, yet it is unknown how B cells integrate pathogen-induced signals to drive or suppress transcriptional programs specialized for each class of pathogen. Here, we detail the key role of the transcription factor c-Myb in regulating the T-bet-mediated anti-viral program. Deletion of c-Myb in mature B cells significantly increased serum IgG2c and CXCR3 expression by upregulating T-bet, normally suppressed during Th2-cell-mediated responses. Enhanced expression of T-bet resulted in aberrant plasma cell differentiation within the germinal center, mediated by CXCR3 expression. These findings identify a dual role for c-Myb in limiting inappropriate effector responses while coordinating plasma cell differentiation with germinal center egress. Identifying such intrinsic regulators of specialized antibody responses can assist in vaccine design and therapeutic intervention in B-cell-mediated immune disorders. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  17. Coordinated transcriptional regulation of isopentenyl diphosphate biosynthetic pathway enzymes in plastids by phytochrome-interacting factor 5.

    Science.gov (United States)

    Mannen, Kazuto; Matsumoto, Takuro; Takahashi, Seiji; Yamaguchi, Yuta; Tsukagoshi, Masanori; Sano, Ryosuke; Suzuki, Hideyuki; Sakurai, Nozomu; Shibata, Daisuke; Koyama, Tanetoshi; Nakayama, Toru

    2014-01-10

    All isoprenoids are derived from a common C5 unit, isopentenyl diphosphate (IPP). In plants, IPP is synthesized via two distinct pathways; the cytosolic mevalonate pathway and the plastidial non-mevalonate (MEP) pathway. In this study, we used a co-expression analysis to identify transcription factors that coordinately regulate the expression of multiple genes encoding enzymes in the IPP biosynthetic pathway. Some candidates showed especially strong correlations with multiple genes encoding MEP-pathway enzymes. We report here that phytochrome-interacting factor 5 (PIF5), a basic-helix-loop-helix type transcription factor, functions as a positive regulator of the MEP pathway. Its overexpression in T87 suspension cultured cells resulted in increased accumulation of chlorophylls and carotenoids. Detailed analyses of carotenoids by HPLC indicated that some carotenoid biosynthetic pathways were concomitantly up-regulated, possibly as a result of enhanced IPP metabolic flow. Our results also revealed other PIF family proteins that play different roles from that of PIF5 in IPP metabolism. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Methylene bridge regulated geometrical preferences of ligands in cobalt(III) coordination chemistry and phenoxazinone synthase mimicking activity.

    Science.gov (United States)

    Panja, Anangamohan; Shyamal, Milan; Saha, Amrita; Mandal, Tarun Kanti

    2014-04-14

    Two new azide bound cobalt(III) complexes, [Co(L(1))(N3)3] (fac-1) and [Co(L(2))(N3)3] (mer-2), where L(1) is bis(2-pyridylmethyl)amine and L(2) is (2-pyridylmethyl)(2-pyridylethyl)amine, derived from tridentate reduced Schiff-base ligands have been reported. Interestingly, a methylene bridge regulated preferential coordination mode of ligands is noticed in their crystal structures: it is found in a facial arrangement in fac-1 and has a meridional disposition in mer-2. Both complexes show phenoxazinone synthase-like activity and the role of the structural factor on the catalytic activity is also explored. Moreover, the easily reducible cobalt(III) center in mer-2 favors the oxidation of o-aminophenol. The ESI-MS positive spectra together with UV-vis spectroscopy clearly suggest the formation of a catalyst-substrate adduct by substitution of the coordinated azide ions in the catalytic cycle.

  19. The ERK1/2 pathway regulates testosterone synthesis by coordinately regulating the expression of steroidogenic genes in Leydig cells.

    Science.gov (United States)

    Matzkin, Maria Eugenia; Yamashita, Soichi; Ascoli, Mario

    2013-05-06

    Adult mice with a Leydig cell specific deletion of MAPK kinase (MEK) 1 and 2 (Mek1(f)(/)(f);Mek2(-/-);Cre(+)) mice display Leydig cell hypoplasia and hypergonadotropic hypogonadism. We used radioimmunoassays and quantitative PCR to evaluate the function and expression of the Leydig cell genes involved in the conversion of cholesterol to testosterone (Star, Cyp11a1, Hsd3b6, Cyp17a1 and Hsd17b3), androgen metabolism (Srda1 and Dhrs9), and four transcription factors (Creb1, Nr5a1, Nr4a1 and Nr0b1) that regulate the expression of steroidogenic genes. We show that Star, Hsd3b6, Cyp17a1 and Hsd17b3 are downregulated in Ledyig cells of adult Mek1(f)(/)(f);Mek2(-/-);Cre(+) mice whereas Srda1 and Dhrs9 are upregulated and Creb1, Nr5a1, Nr4a1 and Nr0b1 are unchanged or upregulated. Functionally, all the downregulated genes but none of the upregulated genes contribute to the decrease in testosterone synthesis in Leydig cells of adult Mek1(f)(/)(f);Mek2(-/-);Cre(+) mice because they produce low testosterone and dihydrotestosterone when stimulated with hCG or when incubated with testosterone precursors such as progesterone or androstenedione. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  20. MicroRNA 224 Regulates Ion Transporter Expression in Ameloblasts To Coordinate Enamel Mineralization.

    Science.gov (United States)

    Fan, Yi; Zhou, Yachuan; Zhou, Xuedong; Sun, Feifei; Gao, Bo; Wan, Mian; Zhou, Xin; Sun, Jianxun; Xu, Xin; Cheng, Lei; Crane, Janet; Zheng, Liwei

    2015-08-01

    Enamel mineralization is accompanied by the release of protons into the extracellular matrix, which is buffered to regulate the pH value in the local microenvironment. The present study aimed to investigate the role of microRNA 224 (miR-224) as a regulator of SLC4A4 and CFTR, encoding the key buffering ion transporters, in modulating enamel mineralization. miR-224 was significantly downregulated as ameloblasts differentiated, in parallel with upregulation of SLC4A4 and CFTR. Overexpression of miR-224 downregulated SLC4A4 and CFTR expression in cultured human epithelial cells. A microRNA luciferase assay confirmed the specific binding of miR-224 to the 3' untranslated regions (UTRs) of SLC4A4 and CFTR mRNAs, thereby inhibiting protein translation. miR-224 agomir injection in mouse neonatal incisors resulted in normal enamel length and thickness, but with disturbed organization of the prism structure and deficient crystal growth. Moreover, the enamel Ca/P ratio and microhardness were markedly reduced after miR-224 agomir administration. These results demonstrate that miR-224 plays a pivotal role in fine tuning enamel mineralization by modulating SLC4A4 and CFTR to maintain pH homeostasis and support enamel mineralization. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  1. Abscisic acid, sucrose, and auxin coordinately regulate berry ripening process of the Fujiminori grape.

    Science.gov (United States)

    Jia, Haifeng; Xie, Zhenqiang; Wang, Chen; Shangguan, Lingfei; Qian, Ning; Cui, Mengjie; Liu, Zhongjie; Zheng, Ting; Wang, Mengqi; Fang, Jinggui

    2017-07-01

    The aim of this study was to examine the effect of abscisic acid (ABA), sucrose, and auxin on grape fruit development and to assess the mechanism of these three factors on the grape fruit ripening process. Different concentrations of ABA, sucrose, and auxin were used to treat the grape fruit, and the ripening-related indices, such as physiological and molecular level parameters, were analyzed. The activity of BG protein activity was analyzed during the fruit development. Sucrose, ABA, and auxin influenced the grape fruit sugar accumulation in different ways, as well as the volatile compounds, anthocyanin content, and fruit firmness. ABA and sucrose induced, but auxin blocked, the ripening-related gene expression levels, such as softening genes PE, PG, PL, and CELL, anthocyanin genes DFR, CHI, F3H, GST, CHS, and UFGT, and aroma genes Ecar, QR, and EGS. ABA, sucrose, and glucose induced the fruit dry weight accumulation, and auxin mainly enhanced fruit dry weight through seed weight accumulation. In the early development of grape, starch was the main energy storage; in the later, it was glucose and fructose. Sucrose metabolism pathway-related gene expression levels were significant for glucose and fructose accumulation. BG protein activity was important in the regulation of grape ABA content levels. ABA plays a core role in the grape fruit development; sucrose functions in fruit development through two pathways: one was ABA dependent, the other ABA independent. Auxin blocked ABA accumulation to regulate the fruit development process.

  2. Coordination and decision making of regulation, operation, and market activities in power systems

    Science.gov (United States)

    Nakashima, Tomoaki

    Electric power has been traditionally supplied to customers at regulated rates by vertically integrated utilities (VIUs), which own generation, transmission, and distribution systems. However, the regulatory authorities of VIUs are promoting competition in their businesses to lower the price of electric energy. Consequently, in new deregulated circumstances, many suppliers and marketers compete in the generation market, and conflict of interest may often occur over transmission. Therefore, a neutral entity, called an independent system operator (ISO), which operates the power system independently, has been established to give market participants nondiscriminatory access to transmission sectors with a natural monopoly, and to facilitate competition in generation sectors. Several types of ISOs are established at present, with their respective regions and authorities. The ISO receives many requests from market participants to transfer power, and must evaluate the feasibility of their requests under the system's condition. In the near future, regulatory authorities may impose various objectives on the ISOs. Then, based on the regulators' policies, the ISO must determine the optimal schedules from feasible solutions, or change the market participants' requests. In a newly developed power market, market participants will conduct their transactions in order to maximize their profit. The most crucial information in conducting power transactions is price and demand. A direct transaction between suppliers and consumers may become attractive because of its stability of price, while in a power exchange market, gaming and speculation of participants may push up electricity prices considerably. To assist the consumers in making effective decisions, suitable methods for forecasting volatile market price are necessary. This research has been approached from three viewpoints: Firstly, from the system operator's point of view, desirable system operation and power market structure

  3. Cyclin D3 coordinates the cell cycle during differentiation to regulate erythrocyte size and number.

    Science.gov (United States)

    Sankaran, Vijay G; Ludwig, Leif S; Sicinska, Ewa; Xu, Jian; Bauer, Daniel E; Eng, Jennifer C; Patterson, Heide Christine; Metcalf, Ryan A; Natkunam, Yasodha; Orkin, Stuart H; Sicinski, Piotr; Lander, Eric S; Lodish, Harvey F

    2012-09-15

    Genome-wide association studies (GWASs) have identified a genetic variant of moderate effect size at 6p21.1 associated with erythrocyte traits in humans. We show that this variant affects an erythroid-specific enhancer of CCND3. A Ccnd3 knockout mouse phenocopies these erythroid phenotypes, with a dramatic increase in erythrocyte size and a concomitant decrease in erythrocyte number. By examining human and mouse primary erythroid cells, we demonstrate that the CCND3 gene product cyclin D3 regulates the number of cell divisions that erythroid precursors undergo during terminal differentiation, thereby controlling erythrocyte size and number. We illustrate how cell type-specific specialization can occur for general cell cycle components-a finding resulting from the biological follow-up of unbiased human genetic studies.

  4. The CO-Regulation Database (CORD): a tool to identify coordinately expressed genes.

    Science.gov (United States)

    Fahrenbach, John P; Andrade, Jorge; McNally, Elizabeth M

    2014-01-01

    Meta-analysis of gene expression array databases has the potential to reveal information about gene function. The identification of gene-gene interactions may be inferred from gene expression information but such meta-analysis is often limited to a single microarray platform. To address this limitation, we developed a gene-centered approach to analyze differential expression across thousands of gene expression experiments and created the CO-Regulation Database (CORD) to determine which genes are correlated with a queried gene. Using the GEO and ArrayExpress database, we analyzed over 120,000 group by group experiments from gene microarrays to determine the correlating genes for over 30,000 different genes or hypothesized genes. CORD output data is presented for sample queries with focus on genes with well-known interaction networks including p16 (CDKN2A), vimentin (VIM), MyoD (MYOD1). CDKN2A, VIM, and MYOD1 all displayed gene correlations consistent with known interacting genes. We developed a facile, web-enabled program to determine gene-gene correlations across different gene expression microarray platforms. Using well-characterized genes, we illustrate how CORD's identification of co-expressed genes contributes to a better understanding a gene's potential function. The website is found at http://cord-db.org.

  5. Coordinated regulation of cardiac Na(+)/Ca (2+) exchanger and Na (+)-K (+)-ATPase by phospholemman (FXYD1).

    Science.gov (United States)

    Cheung, Joseph Y; Zhang, Xue-Qian; Song, Jianliang; Gao, Erhe; Chan, Tung O; Rabinowitz, Joseph E; Koch, Walter J; Feldman, Arthur M; Wang, JuFang

    2013-01-01

    Phospholemman (PLM) is the founding member of the FXYD family of regulators of ion transport. PLM is a 72-amino acid protein consisting of the signature PFXYD motif in the extracellular N terminus, a single transmembrane (TM) domain, and a C-terminal cytoplasmic tail containing three phosphorylation sites. In the heart, PLM co-localizes and co-immunoprecipitates with Na(+)-K(+)-ATPase, Na(+)/Ca(2+) exchanger, and L-type Ca(2+) channel. The TM domain of PLM interacts with TM9 of the α-subunit of Na(+)-K(+)-ATPase, while its cytoplasmic tail interacts with two small regions (spanning residues 248-252 and 300-304) of the proximal intracellular loop of Na(+)/Ca(2+) exchanger. Under stress, catecholamine stimulation phosphorylates PLM at serine(68), resulting in relief of inhibition of Na(+)-K(+)-ATPase by decreasing K(m) for Na(+) and increasing V(max), and simultaneous inhibition of Na(+)/Ca(2+) exchanger. Enhanced Na(+)-K(+)-ATPase activity lowers intracellular Na(+), thereby minimizing Ca(2+) overload and risks of arrhythmias. Inhibition of Na(+)/Ca(2+) exchanger reduces Ca(2+) efflux, thereby preserving contractility. Thus, the coordinated actions of PLM during stress serve to minimize arrhythmogenesis and maintain inotropy. In acute cardiac ischemia and chronic heart failure, either expression or phosphorylation of PLM or both are altered. PLM regulates important ion transporters in the heart and offers a tempting target for development of drugs to treat heart failure.

  6. SRSF3 represses the expression of PDCD4 protein by coordinated regulation of alternative splicing, export and translation

    Energy Technology Data Exchange (ETDEWEB)

    Park, Seung Kuk; Jeong, Sunjoo, E-mail: sjsj@dankook.ac.kr

    2016-02-05

    Gene expression is regulated at multiple steps, such as transcription, splicing, export, degradation and translation. Considering diverse roles of SR proteins, we determined whether the tumor-related splicing factor SRSF3 regulates the expression of the tumor-suppressor protein, PDCD4, at multiple steps. As we have reported previously, knockdown of SRSF3 increased the PDCD4 protein level in SW480 colon cancer cells. More interestingly, here we showed that the alternative splicing and the nuclear export of minor isoforms of pdcd4 mRNA were repressed by SRSF3, but the translation step was unaffected. In contrast, only the translation step of the major isoform of pdcd4 mRNA was repressed by SRSF3. Therefore, overexpression of SRSF3 might be relevant to the repression of all isoforms of PDCD4 protein levels in most types of cancer cell. We propose that SRSF3 could act as a coordinator of the expression of PDCD4 protein via two mechanisms on two alternatively spliced mRNA isoforms.

  7. Coordinated Regulation Among Progesterone, Prostaglandins, and EGF-Like Factors in Human Ovulatory Follicles.

    Science.gov (United States)

    Choi, Yohan; Wilson, Kalin; Hannon, Patrick R; Rosewell, Katherine L; Brännström, Mats; Akin, James W; Curry, Thomas E; Jo, Misung

    2017-06-01

    In animal models, the luteinizing hormone surge increases progesterone (P4) and progesterone receptor (PGR), prostaglandins (PTGs), and epidermal growth factor (EGF)-like factors that play essential roles in ovulation. However, little is known about the expression, regulation, and function of these key ovulatory mediators in humans. To determine when and how these key ovulatory mediators are induced after the luteinizing hormone surge in human ovaries. Timed periovulatory follicles were obtained from cycling women. Granulosa/lutein cells were collected from in vitro fertilization patients. The in vivo and in vitro expression of PGR, PTG synthases and transporters, and EGF-like factors were examined at the level of messenger RNA and protein. PGR binding to specific genes was assessed. P4 and PTGs in conditioned media were measured. PGR, PTGS2, and AREG expressions dramatically increased in ovulatory follicles at 12 to 18 hours after human chorionic gonadotropin (hCG). In human granulosa/lutein cell cultures, hCG increased P4 and PTG production and the expression of PGR, specific PTG synthases and transporters, and EGF-like factors, mimicking in vivo expression patterns. Inhibitors for P4/PGR and EGF-signaling pathways reduced hCG-induced increases in PTG production and the expression of EGF-like factors. PGR bound to the PTGS2, PTGES, and SLCO2A1 genes. This report demonstrated the time-dependent induction of PGR, AREG, and PTGS2 in human periovulatory follicles. In vitro studies indicated that collaborative actions of P4/PGR and EGF signaling are required for hCG-induced increases in PTG production and potentiation of EGF signaling in human periovulatory granulosa cells.

  8. RNA-Seq Transcriptomic Responses of Full-Thickness Dermal Excision Wounds to Pseudomonas aeruginosa Acute and Biofilm Infection.

    Directory of Open Access Journals (Sweden)

    S L Rajasekhar Karna

    Full Text Available Pseudomonas aeruginosa infections of wounds in clinical settings are major complications whose outcomes are influenced by host responses that are not completely understood. Herein we evaluated transcriptomic changes of wounds as they counter P. aeruginosa infection-first active infection, and then chronic biofilm infection. We used the dermal full-thickness, rabbit ear excisional wound model. We studied the wound response: towards acute infection at 2, 6, and 24 hrs after inoculating 106 bacteria into day-3 wounds; and, towards more chronic biofilm infection of wounds similarly infected for 24 hrs but then treated with topical antibiotic to coerce biofilm growth and evaluated at day 5 and 9 post-infection. The wounds were analyzed for bacterial counts, expression of P. aeruginosa virulence and biofilm-synthesis genes, biofilm morphology, infiltrating immune cells, re-epithelialization, and genome-wide gene expression (RNA-Seq transcriptome. This analysis revealed that 2 hrs after bacterial inoculation into day-3 wounds, the down-regulated genes (infected vs. non-infected of the wound edge were nearly all non-coding RNAs (ncRNAs, comprised of snoRNA, miRNA, and RNU6 pseudogenes, and their down-regulation preceded a general down-regulation of skin-enriched coding gene expression. As the active infection intensified, ncRNAs remained overrepresented among down-regulated genes; however, at 6 and 24 hrs they changed to a different set, which overlapped between these times, and excluded RNU6 pseudogenes but included snRNA components of the major and minor spliceosomes. Additionally, the raw counts of multiple types of differentially-expressed ncRNAs increased on post-wounding day 3 in control wounds, but infection suppressed this increase. After 5 and 9 days, these ncRNA counts in control wounds decreased, whereas they increased in the infected, healing-impaired wounds. These data suggest a sequential and coordinated change in the levels of transcripts

  9. RNA-Seq Transcriptomic Responses of Full-Thickness Dermal Excision Wounds to Pseudomonas aeruginosa Acute and Biofilm Infection

    Science.gov (United States)

    Chen, Tsute; Qian, Li-Wu; Fourcaudot, Andrea B.; Yamane, Kazuyoshi; Chen, Ping; Abercrombie, Johnathan J.; You, Tao; Leung, Kai P.

    2016-01-01

    Pseudomonas aeruginosa infections of wounds in clinical settings are major complications whose outcomes are influenced by host responses that are not completely understood. Herein we evaluated transcriptomic changes of wounds as they counter P. aeruginosa infection—first active infection, and then chronic biofilm infection. We used the dermal full-thickness, rabbit ear excisional wound model. We studied the wound response: towards acute infection at 2, 6, and 24 hrs after inoculating 106 bacteria into day-3 wounds; and, towards more chronic biofilm infection of wounds similarly infected for 24 hrs but then treated with topical antibiotic to coerce biofilm growth and evaluated at day 5 and 9 post-infection. The wounds were analyzed for bacterial counts, expression of P. aeruginosa virulence and biofilm-synthesis genes, biofilm morphology, infiltrating immune cells, re-epithelialization, and genome-wide gene expression (RNA-Seq transcriptome). This analysis revealed that 2 hrs after bacterial inoculation into day-3 wounds, the down-regulated genes (infected vs. non-infected) of the wound edge were nearly all non-coding RNAs (ncRNAs), comprised of snoRNA, miRNA, and RNU6 pseudogenes, and their down-regulation preceded a general down-regulation of skin-enriched coding gene expression. As the active infection intensified, ncRNAs remained overrepresented among down-regulated genes; however, at 6 and 24 hrs they changed to a different set, which overlapped between these times, and excluded RNU6 pseudogenes but included snRNA components of the major and minor spliceosomes. Additionally, the raw counts of multiple types of differentially-expressed ncRNAs increased on post-wounding day 3 in control wounds, but infection suppressed this increase. After 5 and 9 days, these ncRNA counts in control wounds decreased, whereas they increased in the infected, healing-impaired wounds. These data suggest a sequential and coordinated change in the levels of transcripts of multiple

  10. RNA-Seq Transcriptomic Responses of Full-Thickness Dermal Excision Wounds to Pseudomonas aeruginosa Acute and Biofilm Infection.

    Science.gov (United States)

    Karna, S L Rajasekhar; D'Arpa, Peter; Chen, Tsute; Qian, Li-Wu; Fourcaudot, Andrea B; Yamane, Kazuyoshi; Chen, Ping; Abercrombie, Johnathan J; You, Tao; Leung, Kai P

    2016-01-01

    Pseudomonas aeruginosa infections of wounds in clinical settings are major complications whose outcomes are influenced by host responses that are not completely understood. Herein we evaluated transcriptomic changes of wounds as they counter P. aeruginosa infection-first active infection, and then chronic biofilm infection. We used the dermal full-thickness, rabbit ear excisional wound model. We studied the wound response: towards acute infection at 2, 6, and 24 hrs after inoculating 106 bacteria into day-3 wounds; and, towards more chronic biofilm infection of wounds similarly infected for 24 hrs but then treated with topical antibiotic to coerce biofilm growth and evaluated at day 5 and 9 post-infection. The wounds were analyzed for bacterial counts, expression of P. aeruginosa virulence and biofilm-synthesis genes, biofilm morphology, infiltrating immune cells, re-epithelialization, and genome-wide gene expression (RNA-Seq transcriptome). This analysis revealed that 2 hrs after bacterial inoculation into day-3 wounds, the down-regulated genes (infected vs. non-infected) of the wound edge were nearly all non-coding RNAs (ncRNAs), comprised of snoRNA, miRNA, and RNU6 pseudogenes, and their down-regulation preceded a general down-regulation of skin-enriched coding gene expression. As the active infection intensified, ncRNAs remained overrepresented among down-regulated genes; however, at 6 and 24 hrs they changed to a different set, which overlapped between these times, and excluded RNU6 pseudogenes but included snRNA components of the major and minor spliceosomes. Additionally, the raw counts of multiple types of differentially-expressed ncRNAs increased on post-wounding day 3 in control wounds, but infection suppressed this increase. After 5 and 9 days, these ncRNA counts in control wounds decreased, whereas they increased in the infected, healing-impaired wounds. These data suggest a sequential and coordinated change in the levels of transcripts of multiple

  11. The cochaperone BAG3 coordinates protein synthesis and autophagy under mechanical strain through spatial regulation of mTORC1.

    Science.gov (United States)

    Kathage, Barbara; Gehlert, Sebastian; Ulbricht, Anna; Lüdecke, Laura; Tapia, Victor E; Orfanos, Zacharias; Wenzel, Daniela; Bloch, Wilhelm; Volkmer, Rudolf; Fleischmann, Bernd K; Fürst, Dieter O; Höhfeld, Jörg

    2017-01-01

    The cochaperone BAG3 is a central protein homeostasis factor in mechanically strained mammalian cells. It mediates the degradation of unfolded and damaged forms of the actin-crosslinker filamin through chaperone-assisted selective autophagy (CASA). In addition, BAG3 stimulates filamin transcription in order to compensate autophagic disposal and to maintain the actin cytoskeleton under strain. Here we demonstrate that BAG3 coordinates protein synthesis and autophagy through spatial regulation of the mammalian target of rapamycin complex 1 (mTORC1). The cochaperone utilizes its WW domain to contact a proline-rich motif in the tuberous sclerosis protein TSC1 that functions as an mTORC1 inhibitor in association with TSC2. Interaction with BAG3 results in a recruitment of TSC complexes to actin stress fibers, where the complexes act on a subpopulation of mTOR-positive vesicles associated with the cytoskeleton. Local inhibition of mTORC1 is essential to initiate autophagy at sites of filamin unfolding and damage. At the same time, BAG3-mediated sequestration of TSC1/TSC2 relieves mTORC1 inhibition in the remaining cytoplasm, which stimulates protein translation. In human muscle, an exercise-induced association of TSC1 with the cytoskeleton coincides with mTORC1 activation in the cytoplasm. The spatial regulation of mTORC1 exerted by BAG3 apparently provides the basis for a simultaneous induction of autophagy and protein synthesis to maintain the proteome under mechanical strain. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Separate and shared sympathetic outflow to white and brown fat coordinately regulates thermoregulation and beige adipocyte recruitment

    Science.gov (United States)

    Nguyen, Ngoc Ly T.; Barr, Candace L.; Ryu, Vitaly; Cao, Qiang; Bartness, Timothy J.

    2017-01-01

    White adipose tissue (WAT) and brown adipose tissue (BAT) are innervated and regulated by the sympathetic nervous system (SNS). It is not clear, however, whether there are shared or separate central SNS outflows to WAT and BAT that regulate their function. We injected two isogenic strains of pseudorabies virus, a retrograde transneuronal viral tract tracer, with unique fluorescent reporters into interscapular BAT (IBAT) and inguinal WAT (IWAT) of the same Siberian hamsters to define SNS pathways to both. To test the functional importance of SNS coordinated control of BAT and WAT, we exposed hamsters with denervated SNS nerves to IBAT to 4°C for 16–24 h and measured core and fat temperatures and norepinephrine turnover (NETO) and uncoupling protein 1 (UCP1) expression in fat tissues. Overall, there were more SNS neurons innervating IBAT than IWAT across the neuroaxis. However, there was a greater percentage of singly labeled IWAT neurons in midbrain reticular nuclei than singly labeled IBAT neurons. The hindbrain had ~30–40% of doubly labeled neurons while the forebrain had ~25% suggesting shared SNS circuitry to BAT and WAT across the brain. The raphe nucleus, a key region in thermoregulation, had ~40% doubly labeled neurons. Hamsters with IBAT SNS denervation maintained core body temperature during acute cold challenge and had increased beige adipocyte formation in IWAT. They also had increased IWAT NETO, temperature, and UCP1 expression compared with intact hamsters. These data provide strong neuroanatomical and functional evidence of WAT and BAT SNS cross talk for thermoregulation and beige adipocyte formation. PMID:27881398

  13. Bacterial Wound Culture

    Science.gov (United States)

    ... and services. Advertising & Sponsorship: Policy | Opportunities Bacterial Wound Culture Share this page: Was this page helpful? Also known as: Aerobic Wound Culture; Anaerobic Wound Culture Formal name: Culture, wound Related ...

  14. Wound Healing and Care

    Science.gov (United States)

    ... Arrhythmias Abuse Love and Romance Understanding Other People Wound Healing and Care KidsHealth > For Teens > Wound Healing ... stitches or a hospital stay? Different Types of Wounds Most of us think of wounds happening because ...

  15. Basic fibroblast growth factor induces down-regulation of alpha-smooth muscle actin and reduction of myofibroblast areas in open skin wounds.

    Science.gov (United States)

    Ishiguro, Shigeki; Akasaka, Yoshikiyo; Kiguchi, Hideko; Suzuki, Takeya; Imaizumi, Risa; Ishikawa, Yukio; Ito, Kinji; Ishii, Toshiharu

    2009-01-01

    To examine the effects of basic fibroblast growth factor (bFGF) on the inhibition of alpha-smooth muscle actin (alpha-SMA) expression in dermal fibroblasts, we have established two dermal myofibroblastic cell lines positive for alpha-SMA (rat myofibroblasts [RMF] and rat myofibroblast-like [RMFL] cells) and one fibroblastic cell line negative for alpha-SMA (rat fibroblasts cells) as a model of fibroblast differentiation. In contrast to the increased expression of alpha-SMA in RMF and RMFL cells, irrespective of transforming growth factor-beta1 treatment, bFGF induced a decrease in alpha-SMA expression in the myofibroblastic cells and the reduced expression patterns of alpha-SMA differed between cells, as demonstrated by Western blot and reverse transcription polymerase chain reaction analyses. Along with the inhibition of alpha-SMA expression by bFGF, the RMF and RMFL cells also showed different activated expression of extracellular signal-regulated kinase 1/2, suggesting the involvement of extracellular signal-regulated kinase 1/2 activation in the down-regulation of alpha-SMA expression in myofibroblasts. Furthermore, an in vivo study demonstrated that bFGF administration markedly decreases the area that is positive for alpha-SMA expression in the treated wounds after day 18. In contrast, bFGF administration significantly increased the number of terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) staining and alpha-SMA-positive cells at days 10 and 14, and reduced the double-positive cells rapidly after day 18. Collectively, the current investigation identified bFGF as a potent stimulator for the reduction of the myofibroblastic area in vivo, presumably because of its effects on the down-regulation of alpha-SMA expression as well as rapid induction of apoptosis in myofibroblasts.

  16. Wounded Warriors: Challenges and Care Coordination

    Science.gov (United States)

    2011-01-01

    Emergency Financial Assistance – ID Cards – DEERS – Travel Services – Military Personnel – Lodging – TSGLI  Assistance – Social Service Administration...2012 20 Key Handoffs • Discharge from Inpatient – Lodging  – Inprocessing – finance, order issue, training – Family integration,  TSGLI • Outpatient

  17. Corneal wound healing after excimer laser keratectomy.

    Science.gov (United States)

    Kaji, Yuichi; Yamashita, Hidetoshi; Oshika, Tetsuro

    2003-03-01

    Excimer laser keratectomy is widely used to correct refractive errors. Several complications of excimer laser keratectomy are reported including corneal infection, regression, corneal haze formation, glare and halo. Most of the complications are closely related to the corneal stromal wound healing process. In order to perform the excimer laser keratectomy with minimum complications, we should understand the mechanism of the corneal stroma wound healing process. In addition, such knowledge will help us to regulate the corneal stromal wound healing process in the future. In the present article, we discuss the molecular mechanism of the corneal stromal wound healing process after excimer laser keratectomy and its regulation by anti-inflammatory agents.

  18. Gene expression signature of fibroblast serum response predicts human cancer progression: similarities between tumors and wounds.

    Directory of Open Access Journals (Sweden)

    Howard Y Chang

    2004-02-01

    Full Text Available Cancer invasion and metastasis have been likened to wound healing gone awry. Despite parallels in cellular behavior between cancer progression and wound healing, the molecular relationships between these two processes and their prognostic implications are unclear. In this study, based on gene expression profiles of fibroblasts from ten anatomic sites, we identify a stereotyped gene expression program in response to serum exposure that appears to reflect the multifaceted role of fibroblasts in wound healing. The genes comprising this fibroblast common serum response are coordinately regulated in many human tumors, allowing us to identify tumors with gene expression signatures suggestive of active wounds. Genes induced in the fibroblast serum-response program are expressed in tumors by the tumor cells themselves, by tumor-associated fibroblasts, or both. The molecular features that define this wound-like phenotype are evident at an early clinical stage, persist during treatment, and predict increased risk of metastasis and death in breast, lung, and gastric carcinomas. Thus, the transcriptional signature of the response of fibroblasts to serum provides a possible link between cancer progression and wound healing, as well as a powerful predictor of the clinical course in several common carcinomas.

  19. Sleeve Gastrectomy Reduces Hepatic Steatosis by Improving the Coordinated Regulation of Aquaglyceroporins in Adipose Tissue and Liver in Obese Rats.

    Science.gov (United States)

    Méndez-Giménez, Leire; Becerril, Sara; Moncada, Rafael; Valentí, Víctor; Ramírez, Beatriz; Lancha, Andoni; Gurbindo, Javier; Balaguer, Inmaculada; Cienfuegos, Javier A; Catalán, Victoria; Fernández, Secundino; Gómez-Ambrosi, Javier; Rodríguez, Amaia; Frühbeck, Gema

    2015-09-01

    Glycerol constitutes an important metabolite for the control of lipid accumulation and glucose homeostasis. Our aim was to investigate the potential role of aquaglyceroporins, which are glycerol channels mediating glycerol efflux in adipocytes (AQP3 and AQP7) and glycerol influx (AQP9) in hepatocytes, in the improvement of adiposity and hepatic steatosis after sleeve gastrectomy in an experimental model of diet-induced obesity (DIO). Male Wistar DIO rats (n = 161) were subjected to surgical (sham operation and sleeve gastrectomy) or dietary interventions [fed ad libitum a normal diet (ND) or a high-fat diet (HFD) or pair-fed to the amount of food eaten by sleeve-gastrectomized animals]. The tissue distribution and expression of AQPs in biopsies of epididymal (EWAT) and subcutaneous (SCWAT) white adipose tissue and liver were analyzed by real-time PCR, Western blot, and immunohistochemistry. Four weeks after surgery, DIO rats undergoing sleeve gastrectomy showed a reduction in body weight, whole-body adiposity, and hepatic steatosis. DIO was associated with a tendency towards an increase in EWAT AQP3 and SCWAT AQP7 and a decrease in hepatic AQP9. Sleeve gastrectomy downregulated AQP7 in both fat depots and upregulated AQP3 in EWAT, without changing hepatic AQP9. Aqp7 transcript levels in EWAT and SCWAT were positively associated with adiposity and glycemia, while Aqp9 mRNA was negatively correlated with markers of hepatic steatosis and insulin resistance. Our results show, for the first time, that sleeve gastrectomy, a widely applied bariatric surgery procedure, restores the coordinated regulation of fat-specific AQP7 and liver-specific AQP9, thereby improving whole-body adiposity and hepatic steatosis.

  20. Nitric oxide and reactive oxygen species coordinately regulate the germination of Puccinia striiformis f. sp. tritici urediniospores

    Directory of Open Access Journals (Sweden)

    Shuining eYin

    2016-02-01

    Full Text Available Nitric oxide (NO and reactive oxygen species (ROS function as signaling molecules in a number of critical signal transduction pathways in plants, including plant biotic interactions. In addition to the role of plant-derived NO and ROS in plant resistance, which has been well documented, pathogen-produced NO and ROS have recently emerged as important players in fungal development and pathogenesis. However, the effects of pathogenic fungi-derived NO and ROS on signaling pathways during fungal pre-infection development remain unknown. Here, using a combination of pharmacological approaches and confocal microscopy, we investigated the roles of NO and ROS during the germination of Puccinia striiformis Westend f. sp. tritici (Pst the wheat stripe rust pathogen. Both NO and ROS have a crucial role in uredinial germination. The scavengers of NO and ROS delayed spore germination and decreased the lengths of germ tubes. A similar phenotype was produced after treatment with the promoter. However, the spores germinated and grew normally when the levels of NO and ROS were simultaneously elevated by the application of a promoter of NO and a donor of ROS. Confocal laser microscopy indicated that both NO and ROS preferentially localized at the germ pores and apexes of growing germ tubes when the ROS/NO ratio in the spores was maintained in a specific range. We concluded that both NO and ROS are critical signaling molecules in the pre-infection development of Pst and that the polar growth of the germ tube is coordinately regulated by NO and ROS.

  1. The Sweet Potato NAC-Domain Transcription Factor IbNAC1 Is Dynamically Coordinated by the Activator IbbHLH3 and the Repressor IbbHLH4 to Reprogram the Defense Mechanism against Wounding

    Science.gov (United States)

    Chen, Shi-Peng; Kuo, Chih-Hsien; Lu, Hsueh-Han; Lo, Hui-Shan; Yeh, Kai-Wun

    2016-01-01

    IbNAC1 is known to activate the defense system by reprogramming a genetic network against herbivory in sweet potato. This regulatory activity elevates plant defense potential but relatively weakens plants by IbNAC1-mediated JA response. The mechanism controlling IbNAC1 expression to balance plant vitality and survival remains unclear. In this study, a wound-responsive G-box cis-element in the IbNAC1 promoter from -1484 to -1479 bp was identified. From a screen of wound-activated transcriptomic data, one transcriptional activator, IbbHLH3, and one repressor, IbbHLH4, were selected that bind to and activate or repress, respectively, the G-box motif in the IbNAC1 promoter to modulate the IbNAC1-mediated response. In the early wound response, the IbbHLH3-IbbHLH3 protein complex binds to the G-box motif to activate IbNAC1 expression. Thus, an elegant defense network is activated against wounding stress. Until the late stages of wounding, IbbHLH4 interacts with IbbHLH3, and the IbbHLH3-IbbHLH4 heterodimer competes with the IbbHLH3-IbbHLH3 complex to bind the G-box and suppress IbNAC1 expression and timely terminates the defense network. Moreover, the JAZs and IbEIL1 proteins interact with IbbHLH3 to repress the transactivation function of IbbHLH3 in non-wounded condition, but their transcription is immediately inhibited upon early wounding. Our work provides a genetic model that accurately switches the regulatory mechanism of IbNAC1 expression to adjust wounding physiology and represents a delicate defense regulatory network in plants. PMID:27780204

  2. Involvement of Abscisic Acid in the Coordinated Regulation of a Stress-Inducible Hexose Transporter (VvHT5) and a Cell Wall Invertase in Grapevine in Response to Biotrophic Fungal Infection[W

    Science.gov (United States)

    Hayes, Matthew A.; Feechan, Angela; Dry, Ian B.

    2010-01-01

    Biotrophic fungal and oomycete pathogens alter carbohydrate metabolism in infected host tissues. Symptoms such as elevated soluble carbohydrate concentrations and increased invertase activity suggest that a pathogen-induced carbohydrate sink is established. To identify pathogen-induced regulators of carbohydrate sink strength, quantitative real-time polymerase chain reaction was used to measure transcript levels of invertase and hexose transporter genes in biotrophic pathogen-infected grapevine (Vitis vinifera) leaves. The hexose transporter VvHT5 was highly induced in coordination with the cell wall invertase gene VvcwINV by powdery and downy mildew infection. However, similar responses were also observed in response to wounding, suggesting that this is a generalized response to stress. Analysis of the VvHT5 promoter region indicated the presence of multiple abscisic acid (ABA) response elements, suggesting a role for ABA in the transition from source to sink under stress conditions. ABA treatment of grape leaves was found to reproduce the same gene-specific transcriptional changes as observed under biotic and abiotic stress conditions. Furthermore, the key regulatory ABA biosynthetic gene, VvNCED1, was activated under these same stress conditions. VvHT5 promoter::β-glucuronidase-directed expression in transgenic Arabidopsis (Arabidopsis thaliana) was activated by infection with powdery mildew and by ABA treatment, and the expression was closely associated with vascular tissue adjacent to infected regions. Unlike VvHT1 and VvHT3, which appear to be predominantly involved in hexose transport in developing leaves and berries, VvHT5 appears to have a specific role in enhancing sink strength under stress conditions, and this is controlled through ABA. Our data suggest a central role for ABA in the regulation of VvcwINV and VvHT5 expression during the transition from source to sink in response to infection by biotrophic pathogens. PMID:20348211

  3. Investigation of coordination and order in transcription regulation of innate and adaptive immunity genes in type 1 diabetes.

    Science.gov (United States)

    Gao, Shouguo; Wolanyk, Nathaniel; Chen, Ye; Jia, Shuang; Hessner, Martin J; Wang, Xujing

    2017-01-31

    Type 1 diabetes (T1D) is an autoimmune disease and extensive evidence has indicated a critical role of both the innate and the adaptive arms of immune system in disease development. To date most clinical trials of immunomodulation therapies failed to show efficacy. A number of gene expression studies of T1D have been carried out. However, a systems analysis of the expression variations of the innate and adaptive immunity gene sets, or their co-expression network structures in cohorts at different disease states or of different disease risks, is not available till now. We utilized data from a large gene expression study that included transcription profiles of control peripheral blood mononuclear cells (PBMC) exposed to plasma of 148 human subjects from four cohorts that included unrelated healthy controls (uHC), recent onset T1D patients (RO-T1D), and healthy siblings of probands that possess high (HRS, High Risk Sibling) or low (LRS, Low Risk Sibling) risk HLA haplotypes. Both weighted and non-weighted co-expression networks were constructed in each cohort separately, and edge weight distribution and the activation of known protein complexes were examined. The co-expression networks of the innate and adaptive immunity genes were further examined in more detail through a number of network measures that included network density, Shannon entropy, h-index, and the scaling exponent γ of degree distribution. Pathway analysis was carried out using CoGA, a tool for detecting significant network structural changes of a gene set. Weighted network edge distribution revealed a globally weakened co-expression network induced by the RO-T1D cohort as compared to that by the uHC, suggesting a broad spectrum loss of transcriptional coordination. The two healthy T1D family cohorts (HRS and LRS) induced more active but heterogeneous transcription coordination globally, and among both the innate and the adaptive immunity genes, than the uHC. This finding is consistent with our

  4. Chronic Wound Healing: A Review of Current Management and Treatments.

    Science.gov (United States)

    Han, George; Ceilley, Roger

    2017-03-01

    Wound healing is a complex, highly regulated process that is critical in maintaining the barrier function of skin. With numerous disease processes, the cascade of events involved in wound healing can be affected, resulting in chronic, non-healing wounds that subject the patient to significant discomfort and distress while draining the medical system of an enormous amount of resources. The healing of a superficial wound requires many factors to work in concert, and wound dressings and treatments have evolved considerably to address possible barriers to wound healing, ranging from infection to hypoxia. Even optimally, wound tissue never reaches its pre-injured strength and multiple aberrant healing states can result in chronic non-healing wounds. This article will review wound healing physiology and discuss current approaches for treating a wound.

  5. Biomaterials and Nanotherapeutics for Enhancing Skin Wound Healing

    Directory of Open Access Journals (Sweden)

    Subhamoy Das

    2016-10-01

    Full Text Available Wound healing is an intricate process that requires complex coordination between many cells and an appropriate extracellular microenvironment. Chronic wounds often suffer from high protease activity, persistent infection, excess inflammation, and hypoxia. While there has been intense investigation to find new methods to improve cutaneous wound care; the management of chronic wounds, burns, and skin wound infection remain challenging clinical problems. Ideally, advanced wound dressings can provide enhanced healing and bridge the gaps in the healing processes that prevent chronic wounds from healing. These technologies have great potential for improving outcomes in patients with poorly healing wounds but face significant barriers in addressing the heterogeneity and clinical complexity of chronic or severe wounds. Active wound dressings aim to enhance the natural healing process and work to counter many aspects that plague poorly healing wounds including excessive inflammation, ischemia, scarring and wound infection. This review paper discusses recent advances in the development of biomaterials and nanoparticle therapeutics to enhance wound healing. In particular, this review focuses on the novel cutaneous wound treatments that have undergone significant preclinical development or currently used in clinical practice.

  6. Coordination of Myeloid Differentiation with Reduced Cell Cycle Progression by PU.1 Induction of MicroRNAs Targeting Cell Cycle Regulators and Lipid Anabolism.

    Science.gov (United States)

    Solomon, Lauren A; Podder, Shreya; He, Jessica; Jackson-Chornenki, Nicholas L; Gibson, Kristen; Ziliotto, Rachel G; Rhee, Jess; DeKoter, Rodney P

    2017-05-15

    During macrophage development, myeloid progenitor cells undergo terminal differentiation coordinated with reduced cell cycle progression. Differentiation of macrophages from myeloid progenitors is accompanied by increased expression of the E26 transformation-specific transcription factor PU.1. Reduced PU.1 expression leads to increased proliferation and impaired differentiation of myeloid progenitor cells. It is not understood how PU.1 coordinates macrophage differentiation with reduced cell cycle progression. In this study, we utilized cultured PU.1-inducible myeloid cells to perform genome-wide chromatin immunoprecipitation sequencing (ChIP-seq) analysis coupled with gene expression analysis to determine targets of PU.1 that may be involved in regulating cell cycle progression. We found that genes encoding cell cycle regulators and enzymes involved in lipid anabolism were directly and inducibly bound by PU.1 although their steady-state mRNA transcript levels were reduced. Inhibition of lipid anabolism was sufficient to reduce cell cycle progression in these cells. Induction of PU.1 reduced expression of E2f1, an important activator of genes involved in cell cycle and lipid anabolism, indirectly through microRNA 223. Next-generation sequencing identified microRNAs validated as targeting cell cycle and lipid anabolism for downregulation. These results suggest that PU.1 coordinates cell cycle progression with differentiation through induction of microRNAs targeting cell cycle regulators and lipid anabolism. Copyright © 2017 American Society for Microbiology.

  7. Irradiation at 660 nm modulates different genes central to wound healing in wounded and diabetic wounded cell models

    Science.gov (United States)

    Houreld, Nicolette N.

    2014-02-01

    Wound healing is a highly orchestrated process and involves a wide variety of cellular components, chemokines and growth factors. Laser irradiation has influenced gene expression and release of various growth factors, cytokines and extracellular matrix proteins involved in wound healing. This study aimed to determine the expression profile of genes involved in wound healing in wounded and diabetic wounded fibroblast cells in response to irradiation at a wavelength of 660 nm. Human skin fibroblast cells (WS1) were irradiated with a diode laser (wavelength 660 nm; fluence 5 J/cm2; power output 100 mW; power density 11 mW/cm2; spot size 9.1 cm2; exposure duration 7 min 35 s). Total RNA was isolated and 1 μg reverse transcribed into cDNA which was used as a template in real-time qualitative polymerase chain reaction (qPCR). Eighty four genes involved in wound healing (extracellular matrix and cell adhesion; inflammatory cytokines and chemokines; growth factors; and signal transduction) were evaluated in wounded and diabetic wounded cell models. Forty eight hours post-irradiation, 6 genes were significantly upregulated and 8 genes were down-regulated in irradiated wounded cells, whereas 1 gene was up-regulated and 33 genes down-regulated in irradiated diabetic wounded cells. Irradiation of stressed fibroblast cells to a wavelength of 660 nm and a fluence of 5 J/cm2 modulated the expression of different genes involved in wound healing in different cell models. Modulation of these genes leads to the effects of laser irradiation seen both in vivo and in vitro, and facilitates the wound healing process.

  8. Fibromodulin Enhances Angiogenesis during Cutaneous Wound Healing

    Directory of Open Access Journals (Sweden)

    Zhong Zheng, PhD

    2014-12-01

    Conclusions: Altogether, we demonstrated that in addition to reducing scar formation, FMOD also promotes angiogenesis. As blood vessels organize and regulate wound healing, its potent angiogenic properties will further expand the clinical application of FMOD for cutaneous healing of poorly vascularized wounds.

  9. Joint Decision-Making and the Coordination of a Sustainable Supply Chain in the Context of Carbon Tax Regulation and Fairness Concerns.

    Science.gov (United States)

    Liu, Zhi; Zheng, Xiao-Xue; Gong, Ben-Gang; Gui, Yun-Miao

    2017-11-27

    Carbon tax regulation and consumers' low-carbon preference act as incentives for firms to abate emissions. Manufacturers can improve product sustainability and retailers can strengthen the promotion of low-carbon products as part of such abatement. Current incomplete rationality also affects product sustainability and low-carbon promotion level. In this context, we consider a supply chain with a manufacturer and a retailer and investigate the impacts of the manufacturer's and the retailer's fairness concerns on their production sustainability level, low-carbon promotion level and profitability. We also explore the coordination contract. The results show that the manufacturer's and the retailer's fairness concerns decrease their product sustainability and low-carbon promotion level, together with the profits of the system and the manufacturer. With regard to the retailer's fairness concern, the product sustainability level and the manufacturer's profit are lower; moreover, the low-carbon promotion level and the profits of the supply chain and the retailer are higher. A revenue-sharing contract can coordinate the supply chain perfectly; however, members' fairness concerns increase the difficulty of coordination. Finally, the numerical results reveal that carbon tax regulation can encourage the manufacturer to enhance the product sustainability level. Further, the impacts on the low-carbon promotion level and firms' profitability are related to the cost coefficients of product sustainability.

  10. Joint Decision-Making and the Coordination of a Sustainable Supply Chain in the Context of Carbon Tax Regulation and Fairness Concerns

    Directory of Open Access Journals (Sweden)

    Zhi Liu

    2017-11-01

    Full Text Available Carbon tax regulation and consumers’ low-carbon preference act as incentives for firms to abate emissions. Manufacturers can improve product sustainability and retailers can strengthen the promotion of low-carbon products as part of such abatement. Current incomplete rationality also affects product sustainability and low-carbon promotion level. In this context, we consider a supply chain with a manufacturer and a retailer and investigate the impacts of the manufacturer’s and the retailer’s fairness concerns on their production sustainability level, low-carbon promotion level and profitability. We also explore the coordination contract. The results show that the manufacturer’s and the retailer’s fairness concerns decrease their product sustainability and low-carbon promotion level, together with the profits of the system and the manufacturer. With regard to the retailer’s fairness concern, the product sustainability level and the manufacturer’s profit are lower; moreover, the low-carbon promotion level and the profits of the supply chain and the retailer are higher. A revenue-sharing contract can coordinate the supply chain perfectly; however, members’ fairness concerns increase the difficulty of coordination. Finally, the numerical results reveal that carbon tax regulation can encourage the manufacturer to enhance the product sustainability level. Further, the impacts on the low-carbon promotion level and firms’ profitability are related to the cost coefficients of product sustainability.

  11. Angiotensin II inhibitor facilitates epidermal wound regeneration in diabetic mice

    Directory of Open Access Journals (Sweden)

    Maria eKamber

    2015-06-01

    Full Text Available Tissue regeneration and wound healing are severely impaired in diabetes and are associated with poor circulation and dysfunctional blood vessels. Angiotensin II inhibitors are anti-hypertensive drugs used in clinical practice to regulate blood pressure and could affect tissue remodeling. We hypothesize that blocking angiotensin II, using Losartan, could facilitate tissue regeneration in diabetic mice. To this end, we established an experimental model of wound healing in streptozotocin-induced diabetic mice. Our data demonstrated that Losartan accelerates wound repair and normalizes wound stromal responses, having a beneficial role in diabetic wounds. Our findings highlight a potential therapeutic use of Losartan in improving wound repair in diabetic conditions.

  12. Botanical Drug Puerarin Coordinates with Nerve Growth Factor in the Regulation of Neuronal Survival and Neuritogenesis via Activating ERK1/2 and PI3K/Akt Signaling Pathways in the Neurite Extension Process

    National Research Council Canada - National Science Library

    Zhao, Jia; Cheng, Yuan‐Yuan; Fan, Wen; Yang, Chuan‐Bin; Ye, Shui‐Fen; Cui, Wei; Wei, Wei; Lao, Li‐Xing; Cai, Jing; Han, Yi‐Fan; Rong, Jian‐Hui

    2015-01-01

    .... This study was designed to investigate whether botanical drug C-glucosylated isoflavone puerarin coordinates with NGF to regulate neuritogenesis via activating ERK1/2 and PI3K/Akt in neurite extension process...

  13. Coordinate up-regulation of low-density lipoprotein receptor and cyclo-oxygenase-2 gene expression in human colorectal cells and in colorectal adenocarcinoma biopsies

    Science.gov (United States)

    Lum, D. F.; McQuaid, K. R.; Gilbertson, V. L.; Hughes-Fulford, M.

    1999-01-01

    Many colorectal cancers have high levels of cyclo-oxygenase 2 (COX-2), an enzyme that metabolizes the essential fatty acids into prostaglandins. Since the low-density lipoprotein receptor (LDLr) is involved in the uptake of essential fatty acids, we studied the effect of LDL on growth and gene regulation in colorectal cancer cells. DiFi cells grown in lipoprotein-deficient sera (LPDS) grew more slowly than cells with LDL. LDLr antibody caused significant inhibition of tumor cell growth but did not affect controls. In addition, LDL uptake did not change in the presence of excess LDL, suggesting that ldlr mRNA lacks normal feedback regulation in some colorectal cancers. Analysis of the ldlr mRNA showed that excess LDL in the medium did not cause down-regulation of the message even after 24 hr. The second portion of the study examined the mRNA expression of ldlr and its co-regulation with cox-2 in normal and tumor specimens from patients with colorectal adenocarcinomas. The ratio of tumor:paired normal mucosa of mRNA expression of ldlr and of cox-2 was measured in specimens taken during colonoscopy. ldlr and cox-2 transcripts were apparent in 11 of 11 carcinomas. There was significant coordinate up-regulation both of ldlr and of cox-2 in 6 of 11 (55%) tumors compared with normal colonic mucosa. There was no up-regulation of cox-2 without concomitant up-regulation of ldlr. These data suggest that the LDLr is abnormally regulated in some colorectal tumors and may play a role in the up-regulation of cox-2. Copyright 1999 Wiley-Liss, Inc.

  14. Saliva and wound healing

    NARCIS (Netherlands)

    Brand, H.S.; Ligtenberg, A.J.M.; Veerman, E.C.I.; Ligtenberg, A.J.M.; Veerman, E.C.I.

    2014-01-01

    Oral wounds heal faster and with less scar formation than skin wounds. One of the key factors involved is saliva, which promotes wound healing in several ways. Saliva creates a humid environment, thus improving the survival and functioning of inflammatory cells that are crucial for wound healing. In

  15. Wound debridement optimisation

    DEFF Research Database (Denmark)

    Ågren, Sven Per Magnus

    2014-01-01

    Wound debridement, the removal of contaminated tissue and senescent cells, is the cornerstone in the care of patients with chronic wounds.......Wound debridement, the removal of contaminated tissue and senescent cells, is the cornerstone in the care of patients with chronic wounds....

  16. Shock Wave Treatment Enhances Cell Proliferation and Improves Wound Healing by ATP Release-coupled Extracellular Signal-regulated Kinase (ERK) Activation*

    Science.gov (United States)

    Weihs, Anna M.; Fuchs, Christiane; Teuschl, Andreas H.; Hartinger, Joachim; Slezak, Paul; Mittermayr, Rainer; Redl, Heinz; Junger, Wolfgang G.; Sitte, Harald H.; Rünzler, Dominik

    2014-01-01

    Shock wave treatment accelerates impaired wound healing in diverse clinical situations. However, the mechanisms underlying the beneficial effects of shock waves have not yet been fully revealed. Because cell proliferation is a major requirement in the wound healing cascade, we used in vitro studies and an in vivo wound healing model to study whether shock wave treatment influences proliferation by altering major extracellular factors and signaling pathways involved in cell proliferation. We identified extracellular ATP, released in an energy- and pulse number-dependent manner, as a trigger of the biological effects of shock wave treatment. Shock wave treatment induced ATP release, increased Erk1/2 and p38 MAPK activation, and enhanced proliferation in three different cell types (C3H10T1/2 murine mesenchymal progenitor cells, primary human adipose tissue-derived stem cells, and a human Jurkat T cell line) in vitro. Purinergic signaling-induced Erk1/2 activation was found to be essential for this proliferative effect, which was further confirmed by in vivo studies in a rat wound healing model where shock wave treatment induced proliferation and increased wound healing in an Erk1/2-dependent fashion. In summary, this report demonstrates that shock wave treatment triggers release of cellular ATP, which subsequently activates purinergic receptors and finally enhances proliferation in vitro and in vivo via downstream Erk1/2 signaling. In conclusion, our findings shed further light on the molecular mechanisms by which shock wave treatment exerts its beneficial effects. These findings could help to improve the clinical use of shock wave treatment for wound healing. PMID:25118288

  17. Shock wave treatment enhances cell proliferation and improves wound healing by ATP release-coupled extracellular signal-regulated kinase (ERK) activation.

    Science.gov (United States)

    Weihs, Anna M; Fuchs, Christiane; Teuschl, Andreas H; Hartinger, Joachim; Slezak, Paul; Mittermayr, Rainer; Redl, Heinz; Junger, Wolfgang G; Sitte, Harald H; Rünzler, Dominik

    2014-09-26

    Shock wave treatment accelerates impaired wound healing in diverse clinical situations. However, the mechanisms underlying the beneficial effects of shock waves have not yet been fully revealed. Because cell proliferation is a major requirement in the wound healing cascade, we used in vitro studies and an in vivo wound healing model to study whether shock wave treatment influences proliferation by altering major extracellular factors and signaling pathways involved in cell proliferation. We identified extracellular ATP, released in an energy- and pulse number-dependent manner, as a trigger of the biological effects of shock wave treatment. Shock wave treatment induced ATP release, increased Erk1/2 and p38 MAPK activation, and enhanced proliferation in three different cell types (C3H10T1/2 murine mesenchymal progenitor cells, primary human adipose tissue-derived stem cells, and a human Jurkat T cell line) in vitro. Purinergic signaling-induced Erk1/2 activation was found to be essential for this proliferative effect, which was further confirmed by in vivo studies in a rat wound healing model where shock wave treatment induced proliferation and increased wound healing in an Erk1/2-dependent fashion. In summary, this report demonstrates that shock wave treatment triggers release of cellular ATP, which subsequently activates purinergic receptors and finally enhances proliferation in vitro and in vivo via downstream Erk1/2 signaling. In conclusion, our findings shed further light on the molecular mechanisms by which shock wave treatment exerts its beneficial effects. These findings could help to improve the clinical use of shock wave treatment for wound healing. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Polo-Like Kinase 2 is Dynamically Regulated to Coordinate Proliferation and Early Lineage Specification Downstream of Yes-Associated Protein 1 in Cardiac Progenitor Cells.

    Science.gov (United States)

    Mochizuki, Michika; Lorenz, Vera; Ivanek, Robert; Della Verde, Giacomo; Gaudiello, Emanuele; Marsano, Anna; Pfister, Otmar; Kuster, Gabriela M

    2017-10-24

    Recent studies suggest that adult cardiac progenitor cells (CPCs) can produce new cardiac cells. Such cell formation requires an intricate coordination of progenitor cell proliferation and commitment, but the molecular cues responsible for this regulation in CPCs are ill defined. Extracellular matrix components are important instructors of cell fate. Using laminin and fibronectin, we induced two slightly distinct CPC phenotypes differing in proliferation rate and commitment status and analyzed the early transcriptomic response to CPC adhesion (Yes-associated protein (YAP) conserved signature and TEA domain family member 1 (TEAD1)-related genes. This early gene regulation was preceded by the rapid cytosolic sequestration and degradation of YAP on laminin. Among the most strongly regulated genes was polo-like kinase 2 (Plk2). Plk2 expression depended on YAP stability and was enhanced in CPCs transfected with a nuclear-targeted mutant YAP. Phenotypically, the early downregulation of Plk2 on laminin was succeeded by lower cell proliferation, enhanced lineage gene expression (24 hours), and facilitated differentiation (3 weeks) compared with fibronectin. Finally, overexpression of Plk2 enhanced CPC proliferation and knockdown of Plk2 induced the expression of lineage genes. Plk2 acts as coordinator of cell proliferation and early lineage commitment in CPCs. The rapid downregulation of Plk2 on YAP inactivation marks a switch towards enhanced commitment and facilitated differentiation. These findings link early gene regulation to cell fate and provide novel insights into how CPC proliferation and differentiation are orchestrated. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  19. Complex Interplay between FleQ, Cyclic Diguanylate and Multiple σ Factors Coordinately Regulates Flagellar Motility and Biofilm Development in Pseudomonas putida.

    Directory of Open Access Journals (Sweden)

    Alicia Jiménez-Fernández

    Full Text Available Most bacteria alternate between a free living planktonic lifestyle and the formation of structured surface-associated communities named biofilms. The transition between these two lifestyles requires a precise and timely regulation of the factors involved in each of the stages that has been likened to a developmental process. Here we characterize the involvement of the transcriptional regulator FleQ and the second messenger cyclic diguanylate in the coordinate regulation of multiple functions related to motility and surface colonization in Pseudomonas putida. Disruption of fleQ caused strong defects in flagellar motility, biofilm formation and surface attachment, and the ability of this mutation to suppress multiple biofilm-related phenotypes associated to cyclic diguanylate overproduction suggests that FleQ mediates cyclic diguanylate signaling critical to biofilm growth. We have constructed a library containing 94 promoters potentially involved in motility and biofilm development fused to gfp and lacZ, screened this library for FleQ and cyclic diguanylate regulation, and assessed the involvement of alternative σ factors σN and FliA in the transcription of FleQ-regulated promoters. Our results suggest a dual mode of action for FleQ. Low cyclic diguanylate levels favor FleQ interaction with σN-dependent promoters to activate the flagellar cascade, encompassing the flagellar cluster and additional genes involved in cyclic diguanylate metabolism, signal transduction and gene regulation. On the other hand, characterization of the FleQ-regulated σN- and FliA-independent PlapA and PbcsD promoters revealed two disparate regulatory mechanisms leading to a similar outcome: the synthesis of biofilm matrix components in response to increased cyclic diguanylate levels.

  20. uPA dependent and independent mechanisms of wound healing by C-phycocyanin

    Science.gov (United States)

    Madhyastha, H K; Radha, K S; Nakajima, Y; Omura, S; Maruyama, M

    2008-01-01

    Wound repair requires both recruitment and well co-ordinated actions of many cell types including inflammatory cells, endothelial cells, epithelial cells and importantly fibroblast cells. Urokinase-type plasminogen activator (uPA) system plays a vital role in wound healing phenomenon. We have previously demonstrated that C-phycocyanin (C-pc), a biliprotein from blue-green algae, transcriptionally regulates uPA through cAMP-dependent protein kinase A (PKA) pathway. To date, a role for C-pc in wound-healing scenario is not elucidated. This study was designed to examine the wound-healing property of C-pc in relation to fibroblast proliferation and migration. C-pc increased fibroblast proliferation in a dose-dependent manner. It also enhanced G1 phase of cell cycle and increased the expressions of cyclin-dependent kinases 1 and 2, which facilitate cell cycle progression, in a uPA-independent manner. In vitro wound healing and migration assays revealed the pro-migratory properties of C-pc. Short-interference RNA studies demonstrated that uPA was necessary for C-pc-induced fibroblast migration. C-pc also significantly elevated the expressions of chemokines (MDC, RANTES, Eotaxin, GRO α, ENA78 and TARC) and Rho-GTPases (Cdc 42 and Rac 1) in a uPA-dependent manner. Pre-treatment of C-pc-stimulated cells with pharmacological inhibitor of PI-3K (LY294002) annulled the expression of GTPases implying that Rac 1 and Cdc 42 were induced through PI-3K pathway. C-pc-induced cellular migration towards wounded area was also negatively affected by PI-3K inhibition. In vivo wound-healing experiments in mice validated our finding that C-pc accelerates wound healing. Our data provides conclusive evidence of a novel therapeutic usage for C-pc as a wound-healing agent. C-pc is a food and drug administration (FDA)-approved health supplement. We believe this compound can also be beneficial in healing of internal wounds, such as ulcers. PMID:18266963

  1. Targeted systems biology profiling of tomato fruit reveals coordination of the Yang cycle and a distinct regulation of ethylene biosynthesis during postclimacteric ripening.

    Science.gov (United States)

    Van de Poel, Bram; Bulens, Inge; Markoula, Aikaterina; Hertog, Maarten L A T M; Dreesen, Rozemarijn; Wirtz, Markus; Vandoninck, Sandy; Oppermann, Yasmin; Keulemans, Johan; Hell, Ruediger; Waelkens, Etienne; De Proft, Maurice P; Sauter, Margret; Nicolai, Bart M; Geeraerd, Annemie H

    2012-11-01

    The concept of system 1 and system 2 ethylene biosynthesis during climacteric fruit ripening was initially described four decades ago. Although much is known about fruit development and climacteric ripening, little information is available about how ethylene biosynthesis is regulated during the postclimacteric phase. A targeted systems biology approach revealed a novel regulatory mechanism of ethylene biosynthesis of tomato (Solanum lycopersicum) when fruit have reached their maximal ethylene production level and which is characterized by a decline in ethylene biosynthesis. Ethylene production is shut down at the level of 1-aminocyclopropane-1-carboxylic acid oxidase. At the same time, 1-aminocyclopropane-1-carboxylic acid synthase activity increases. Analysis of the Yang cycle showed that the Yang cycle genes are regulated in a coordinated way and are highly expressed during postclimacteric ripening. Postclimacteric red tomatoes on the plant showed only a moderate regulation of 1-aminocyclopropane-1-carboxylic acid synthase and Yang cycle genes compared with the regulation in detached fruit. Treatment of red fruit with 1-methylcyclopropane and ethephon revealed that the shut-down mechanism in ethylene biosynthesis is developmentally programmed and only moderately ethylene sensitive. We propose that the termination of autocatalytic ethylene biosynthesis of system 2 in ripe fruit delays senescence and preserves the fruit until seed dispersal.

  2. Role of tomato lipoxygenase D in wound-induced jasmonate biosynthesis and plant immunity to insect herbivores.

    Directory of Open Access Journals (Sweden)

    Liuhua Yan

    Full Text Available In response to insect attack and mechanical wounding, plants activate the expression of genes involved in various defense-related processes. A fascinating feature of these inducible defenses is their occurrence both locally at the wounding site and systemically in undamaged leaves throughout the plant. Wound-inducible proteinase inhibitors (PIs in tomato (Solanum lycopersicum provide an attractive model to understand the signal transduction events leading from localized injury to the systemic expression of defense-related genes. Among the identified intercellular molecules in regulating systemic wound response of tomato are the peptide signal systemin and the oxylipin signal jasmonic acid (JA. The systemin/JA signaling pathway provides a unique opportunity to investigate, in a single experimental system, the mechanism by which peptide and oxylipin signals interact to coordinate plant systemic immunity. Here we describe the characterization of the tomato suppressor of prosystemin-mediated responses8 (spr8 mutant, which was isolated as a suppressor of (prosystemin-mediated signaling. spr8 plants exhibit a series of JA-dependent immune deficiencies, including the inability to express wound-responsive genes, abnormal development of glandular trichomes, and severely compromised resistance to cotton bollworm (Helicoverpa armigera and Botrytis cinerea. Map-based cloning studies demonstrate that the spr8 mutant phenotype results from a point mutation in the catalytic domain of TomLoxD, a chloroplast-localized lipoxygenase involved in JA biosynthesis. We present evidence that overexpression of TomLoxD leads to elevated wound-induced JA biosynthesis, increased expression of wound-responsive genes and, therefore, enhanced resistance to insect herbivory attack and necrotrophic pathogen infection. These results indicate that TomLoxD is involved in wound-induced JA biosynthesis and highlight the application potential of this gene for crop protection against

  3. Syndecan-4 proteoglycan cytoplasmic domain and phosphatidylinositol 4,5-bisphosphate coordinately regulate protein kinase C activity

    DEFF Research Database (Denmark)

    Oh, E S; Woods, A; Lim, S T

    1998-01-01

    Phosphatidylinositol 4,5-bisphosphate (PIP2) is involved in the organization of the actin cytoskeleton by regulating actin-associated proteins. The transmembrane heparan sulfate proteoglycan syndecan-4 also plays a critical role in protein kinase C (PKC) signaling in the formation of focal...

  4. Effective approaches to regulate mobile advertising: moving towards a co-ordinated legal, self-regulatory, and technical response

    DEFF Research Database (Denmark)

    Cleff, Evelyne Beatrix

    2009-01-01

    that should be addressed, so that fair information principles can be applied in the context of m-advertising. It also points out the limitations of these principles. Furthermore, the article discusses a range of models that is available for regulating the collection, use and disclosure of personal data...

  5. Extracellular matrix and wound healing.

    Science.gov (United States)

    Maquart, F X; Monboisse, J C

    2014-04-01

    Extracellular matrix has been known for a long time as an architectural support for the tissues. Many recent data, however, have shown that extracellular matrix macromolecules (collagens, elastin, glycosaminoglycans, proteoglycans and connective tissue glycoproteins) are able to regulate many important cell functions, such as proliferation, migration, protein synthesis or degradation, apoptosis, etc., making them able to play an important role in the wound repair process. Not only the intact macromolecules but some of their specific domains, that we called "Matrikines", are also able to regulate many cell activities. In this article, we will summarize main findings showing the effects of extracellular matrix macromolecules and matrikines on connective tissue and epithelial cells, particularly in skin, and their potential implication in the wound healing process. These examples show that extracellular matrix macromolecules or some of their specific domains may play a major role in wound healing. Better knowledge of these interactions may suggest new therapeutic targets in wound healing defects. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  6. Wound Healing Angiogenesis: Innovations and Challenges in Acute and Chronic Wound Healing

    Science.gov (United States)

    Demidova-Rice, Tatiana N.; Durham, Jennifer T.; Herman, Ira M.

    2012-01-01

    Background Formation of new blood vessels, by either angiogenesis or vasculogenesis, is critical for normal wound healing. Major processes in neovascularization include (i) growth-promoting or survival factors, (ii) proteolytic enzymes, (iii) activators of multiple differentiated and progenitor cell types, and (iv) permissible microenvironments. A central aim of wound healing research is to “convert” chronic, disease-impaired wounds into those that will heal. The problem Reduced ability to re-establish a blood supply to the injury site can ultimately lead to wound chronicity. Basic/Clinical Science Advances (1) Human fetal endothelial progenitor cells can stimulate wound revascularization and repair following injury, as demonstrated in a novel mouse model of diabetic ischemic healing. (2) Advances in bioengineering reveal exciting alternatives by which wound repair may be facilitated via the creation of vascularized microfluidic networks within organ constructs created ex vivo for wound implantation. (3) A “personalized” approach to regenerative medicine may be enabled by the identification of protein components present within individual wound beds, both chronic and acute. Clinical Care Relevance Despite the development of numerous therapies, impaired angiogenesis and wound chronicity remain significant healthcare problems. As such, innovations in enhancing wound revascularization would lead to significant advances in wound healing therapeutics and patient care. Conclusion Insights into endothelial progenitor cell biology together with developments in the field of tissue engineering and molecular diagnostics should not only further advance our understanding of the molecular mechanisms regulating wound repair but also offer innovative solutions to promote the healing of chronic and acute wounds in vivo. PMID:24527273

  7. Global Regulator of Virulence A (GrvA) Coordinates Expression of Discrete Pathogenic Mechanisms in Enterohemorrhagic Escherichia coli through Interactions with GadW-GadE.

    Science.gov (United States)

    Morgan, Jason K; Carroll, Ronan K; Harro, Carly M; Vendura, Khoury W; Shaw, Lindsey N; Riordan, James T

    2015-11-02

    Global regulator of virulence A (GrvA) is a ToxR-family transcriptional regulator that activates locus of enterocyte effacement (LEE)-dependent adherence in enterohemorrhagic Escherichia coli (EHEC). LEE activation by GrvA requires the Rcs phosphorelay response regulator RcsB and is sensitive to physiologically relevant concentrations of bicarbonate, a known stimulant of virulence systems in intestinal pathogens. This study determines the genomic scale of GrvA-dependent regulation and uncovers details of the molecular mechanism underlying GrvA-dependent regulation of pathogenic mechanisms in EHEC. In a grvA-null background of EHEC strain TW14359, RNA sequencing analysis revealed the altered expression of over 700 genes, including the downregulation of LEE- and non-LEE-encoded effectors and the upregulation of genes for glutamate-dependent acid resistance (GDAR). Upregulation of GDAR genes corresponded with a marked increase in acid resistance. GrvA-dependent regulation of GDAR and the LEE required gadE, the central activator of GDAR genes and a direct repressor of the LEE. Control of gadE by GrvA was further determined to occur through downregulation of the gadE activator GadW. This interaction of GrvA with GadW-GadE represses the acid resistance phenotype, while it concomitantly activates the LEE-dependent adherence and secretion of immune subversion effectors. The results of this study significantly broaden the scope of GrvA-dependent regulation and its role in EHEC pathogenesis. Enterohemorrhagic Escherichia coli (EHEC) is an intestinal human pathogen causing acute hemorrhagic colitis and life-threatening hemolytic-uremic syndrome. For successful transmission and gut colonization, EHEC relies on the glutamate-dependent acid resistance (GDAR) system and a type III secretion apparatus, encoded on the LEE pathogenicity island. This study investigates the mechanism whereby the DNA-binding regulator GrvA coordinates activation of the LEE with repression of GDAR

  8. Coordinated regulation of photosynthetic and respiratory components is necessary to maintain chloroplast energy balance in varied growth conditions.

    Science.gov (United States)

    Dahal, Keshav; Martyn, Greg D; Alber, Nicole A; Vanlerberghe, Greg C

    2017-01-01

    Mitochondria have a non-energy-conserving alternative oxidase (AOX) proposed to support photosynthesis, perhaps by promoting energy balance under varying growth conditions. To investigate this, wild-type (WT) Nicotiana tabacum were compared with AOX knockdown and overexpression lines. In addition, the amount of AOX protein in WT plants was compared with that of chloroplast light-harvesting complex II (LHCB2), whose amount is known to respond to chloroplast energy status. With increased growth irradiance, WT leaves maintained higher rates of respiration in the light (RL), but no differences in RL or photosynthesis were seen between the WT and transgenic lines, suggesting that, under non-stress conditions, AOX was not critical for leaf metabolism, regardless of growth irradiance. However, under drought, the AOX amount became an important determinant of RL, which in turn was an important determinant of chloroplast energy balance (measured as photosystem II excitation pressure, EP), and photosynthetic performance. In the WT, the AOX amount increased and the LHCB2 amount decreased with increased growth irradiance or drought severity. These changes in protein amounts correlated strongly, in opposing ways, with growth EP. This suggests that a signal deriving from the photosynthetic electron transport chain status coordinately controls the amounts of AOX and LHCB2, which then both contribute to maintaining chloroplast energy balance, particularly under stress conditions. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  9. Solvent-regulated assemblies of four Zn(II) coordination polymers constructed by flexible tetracarboxylates and pyridyl ligands

    Science.gov (United States)

    Fang, Kang; He, Xiang; Shao, Min; Li, Ming-Xing

    2016-08-01

    Four unique complexes with diverse coordination architectures were synthesized upon complexation of 5,5-(1,4-phenylenebis (methylene))bis (oxy)- diisophthalic acid (H4L) with zinc ions by using different solvent. namely, {[Zn(H2L) (bpp)]·DEF}n (1), {[Zn2(L) (bpp)2]·4H2O}n (2), {[Zn2(L) (pdp)2]·3H2O·DEF}n (3), {[Zn2(L) (pdp)2].4H2O}n (4). Complexes 1,2 and 3,4 are obtained by varying solvents to control their structures. The size of solvent molecular plays an important role to control different structure of these compounds. Compound 1 is 2D waved framework with (4, 4) grid layer as sql topology. Compound 3 displays a (4,6)-connected 2-nodal net with a fsc topology. Compounds 2 and 4 are all three-dimensional network simplified as (4,4)-connected 2-nodal net with a bbf topology. The photochemical properties of compounds 1-4 were tested in the solid state at room temperature, owing to their strong luminescent emissions, complexes 1-4 are good candidates for photoactive materials.

  10. Coordinated regulation of photosynthetic and respiratory components is necessary to maintain chloroplast energy balance in varied growth conditions

    Science.gov (United States)

    Dahal, Keshav; Martyn, Greg D.; Alber, Nicole A.

    2017-01-01

    Abstract Mitochondria have a non-energy-conserving alternative oxidase (AOX) proposed to support photosynthesis, perhaps by promoting energy balance under varying growth conditions. To investigate this, wild-type (WT) Nicotiana tabacum were compared with AOX knockdown and overexpression lines. In addition, the amount of AOX protein in WT plants was compared with that of chloroplast light-harvesting complex II (LHCB2), whose amount is known to respond to chloroplast energy status. With increased growth irradiance, WT leaves maintained higher rates of respiration in the light (RL), but no differences in RL or photosynthesis were seen between the WT and transgenic lines, suggesting that, under non-stress conditions, AOX was not critical for leaf metabolism, regardless of growth irradiance. However, under drought, the AOX amount became an important determinant of RL, which in turn was an important determinant of chloroplast energy balance (measured as photosystem II excitation pressure, EP), and photosynthetic performance. In the WT, the AOX amount increased and the LHCB2 amount decreased with increased growth irradiance or drought severity. These changes in protein amounts correlated strongly, in opposing ways, with growth EP. This suggests that a signal deriving from the photosynthetic electron transport chain status coordinately controls the amounts of AOX and LHCB2, which then both contribute to maintaining chloroplast energy balance, particularly under stress conditions. PMID:28011719

  11. How wounds heal

    Science.gov (United States)

    How cuts heal; How scrapes heal; How puncture wounds heal; How burns heal; How pressure sores heal; How lacerations heal ... For major wounds, follow your doctor's instructions on how to care for your injury. Avoid picking at ...

  12. Surgical wound care

    Science.gov (United States)

    ... closing before the wound underneath fills in. Proper Handwashing It is important to clean your hands before ... 5°F (38°C) or higher. Alternative Names Surgical incision care; Open wound care Images Proper hand ...

  13. Surgical wound care -- closed

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000738.htm Surgical wound care - closed To use the sharing features on ... made during surgery. It is also called a "surgical wound." Some incisions are small. Others are very long. ...

  14. ATX and LPA receptor 3 are coordinately up-regulated in lipopolysaccharide-stimulated THP-1 cells through PKR and SPK1-mediated pathways.

    Science.gov (United States)

    Li, Song; Xiong, Chaoyang; Zhang, Junjie

    2012-03-23

    Lysophosphatidic acid (LPA) is an important phospholipid mediator in inflammation and immunity. Previously, we showed that autotaxin (ATX), the enzyme producing LPA from lysophosphatidylcholine (LPC), is induced by LPS in THP-1 cells via the activation of PKR, JNK and p38 MAPK. In this study, we find that ATX and LPA receptor 3 (LPA(3)) are coordinately up-regulated in LPS-stimulated THP-1 cells. PKR-mediated activation of JNK1 and p38 MAPK is required for both ATX and LPA(3) up-regulation. SPK1-mediated activation of the PI3K-AKT-β-catenin pathway is essential for ATX induction, while SPK1-mediated ERK activation is required for LPA(3) up-regulation. Either ATX or LPA(3) knockdown inhibited CCL8 induction by LPS, suggesting that ATX and LPA(3) are involved in CCL8 induction during the inflammatory process against bacterial infection. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  15. Coordinated regulation of IFITM1, 2 and 3 genes by an IFN-responsive enhancer through long-range chromatin interactions.

    Science.gov (United States)

    Li, Ping; Shi, Ming-Lei; Shen, Wen-Long; Zhang, Zhang; Xie, De-Jian; Zhang, Xiang-Yuan; He, Chao; Zhang, Yan; Zhao, Zhi-Hu

    2017-08-01

    Interferon-induced transmembrane protein (IFITM) 1, 2 and 3 genes encode a family of interferon (IFN)-induced transmembrane proteins that block entry of a broad spectrum of pathogens. However, the transcriptional regulation of these genes, especially whether there exist any enhancers and their roles during the IFN induction process remain elusive. Here, through public data mining, episomal luciferase reporter assay and in vivo CRISPR-Cas9 genome editing, we identified an IFN-responsive enhancer located 35kb upstream of IFITM3 gene promoter upregulating the IFN-induced expression of IFITM1, 2 and 3 genes. Chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA) and luciferase reporter assay demonstrated that signal transducers and activators of transcription (STAT) 1 bound to the enhancer with the treatment of IFN and was indispensable for the enhancer activity. Furthermore, using chromosome conformation capture technique, we revealed that the IFITM1, 2 and 3 genes physically clustered together and constitutively looped to the distal enhancer through long-range interactions in both HEK293 and A549 cells, providing structural basis for coordinated regulation of IFITM1, 2 and 3 by the enhancer. Finally, we showed that in vivo truncation of the enhancer impaired IFN-induced resistance to influenza A virus (IAV) infection. These findings expand our understanding of the mechanisms underlying the transcriptional regulation of IFITM1, 2 and 3 expression and its ability to mediate IFN signaling. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Limb immobilization induces a coordinate down-regulation of mitochondrial and other metabolic pathways in men and women.

    Directory of Open Access Journals (Sweden)

    Arkan Abadi

    Full Text Available Advancements in animal models and cell culture techniques have been invaluable in the elucidation of the molecular mechanisms that regulate muscle atrophy. However, few studies have examined muscle atrophy in humans using modern experimental techniques. The purpose of this study was to examine changes in global gene transcription during immobilization-induced muscle atrophy in humans and then explore the effects of the most prominent transcriptional alterations on protein expression and function. Healthy men and women (N = 24 were subjected to two weeks of unilateral limb immobilization, with muscle biopsies obtained before, after 48 hours (48 H and 14 days (14 D of immobilization. Muscle cross sectional area (approximately 5% and strength (10-20% were significantly reduced in men and women (approximately 5% and 10-20%, respectively after 14 D of immobilization. Micro-array analyses of total RNA extracted from biopsy samples at 48 H and 14 D uncovered 575 and 3,128 probes, respectively, which were significantly altered during immobilization. As a group, genes involved in mitochondrial bioenergetics and carbohydrate metabolism were predominant features at both 48 H and 14 D, with genes involved in protein synthesis and degradation significantly down-regulated and up-regulated, respectively, at 14 D of muscle atrophy. There was also a significant decrease in the protein content of mitochondrial cytochrome c oxidase, and the enzyme activity of cytochrome c oxidase and citrate synthase after 14 D of immobilization. Furthermore, protein ubiquitination was significantly increased at 48 H but not 14 D of immobilization. These results suggest that transcriptional and post-transcriptional suppression of mitochondrial processes is sustained throughout 14 D of immobilization, while protein ubiquitination plays an early but transient role in muscle atrophy following short-term immobilization in humans.

  17. HLA-DRB1 may be antagonistically regulated by the coordinately evolved promoter and 3'-UTR under stabilizing selection.

    Directory of Open Access Journals (Sweden)

    Benrong Liu

    Full Text Available HLA-DRB1 is the most polymorphic MHC (major histocompatibility complex class II gene in human, and plays a crucial role in the development and function of the immune system. Extensive polymorphisms exist in the promoter and 3'-UTR of HLA-DRB1, especially a LTR (Long terminal repeat element in the promoter, which may be involved in the expression regulation. However, it remains unknown how the polymorphisms in the whole promoter region and 3'-UTR to regulate the gene expression. In this study, we investigated the extensive polymorphisms in the HLA-DRB1 promoter and 3'-UTR, and how these polymorphisms affect the gene expression in both independent and jointly manners. It was observed that most of the haplotypes in the DRB1 promoter and 3'-UTR were clustered into 4 conserved lineages (H1, H2, H3 and H4, and showed high linkage disequilibrium. Compared with H1 and H2 lineage, a LTR element in the promoter of H3 and H4 lineage significantly suppressed the promoter activity, whereas the activity of the linked 3'-UTR increased, leading to no apparent difference in the final expression product between H1/H2 and H3/H4 lineage. Nevertheless, compared with the plasmid with a promoter and 3'-UTR from the same lineage, the recombinant plasmid with a promoter from H2 and a 3'-UTR from H3 showed about double fold increased luciferase activity, Conversely, the recombinant plasmid with a promoter from H3 and a 3'-UTR from H2 resulted in about 2-fold decreased luciferase activity. These results indicate that the promoter and 3'-UTR of HLA-DRB1 may antagonistically regulate the gene expression, which may be subjected to stabilizing selection. These findings may provide a novel insight into the mechanisms of the diseases associated with HLA-DRB1 genes.

  18. WOUND CARE IN ORTHOPAEDICS

    African Journals Online (AJOL)

    Going hand in hand with training personnel is the need to establish wound care protocols which are totally lacking in developing countries. Negative- pressure wound therapy. This is also known as vacuum dressing, Negative. Pressure Wound Therapy (NPWT). It has turned out to be very useful in burn and extensive skin ...

  19. Saliva and wound healing

    NARCIS (Netherlands)

    Brand, H.S.; Veerman, E.C.I.

    2013-01-01

    Wounds in the oral cavity heal faster and with less scarring than wounds in other parts of the body. One of the factors implicated in this phenomenon is the presence of saliva, which promotes the healing of oral wounds in several ways. Saliva creates a humid environment, which improves the survival

  20. Improved wound care product

    DEFF Research Database (Denmark)

    2012-01-01

    The present invention pertains to use of sodium diacetate (NaHAc 2) as an antimicrobial agent against bacteria growing in biofilms. The aspects of the invention include a wound care product comprising sodium diacetate, a kit comprising a wound care product,and a methodof treating an infected wound....

  1. Effective approaches to regulate mobile advertising: moving towards a co-ordinated legal, self-regulatory, and technical response

    DEFF Research Database (Denmark)

    Cleff, Evelyne Beatrix

    2010-01-01

    This article aims to contribute to the ongoing discourse about the issue of privacy in the mobile advertising domain. The article discusses the fundamental principles and information practices used in digital environments for protecting individuals' private data. Major challenges are identified...... that should be addressed, so that fair information principles can be applied in the context of m-advertising. It also points out the limitations of these principles. Furthermore, the article discusses a range of models that is available for regulating the collection, use and disclosure of personal data...

  2. MicroRNA-183-96-182 Cluster Regulates Bovine Granulosa Cell Proliferation and Cell Cycle Transition by Coordinately Targeting FOXO1.

    Science.gov (United States)

    Gebremedhn, Samuel; Salilew-Wondim, Dessie; Hoelker, Michael; Rings, Franca; Neuhoff, Christiane; Tholen, Ernst; Schellander, Karl; Tesfaye, Dawit

    2016-06-01

    Large-scale expression profiling of micro-RNAs (miRNAs) in bovine granulosa cells from dominant and subordinate follicles on Day 19 of the estrous cycle revealed enriched micro-RNA-183-96-182 cluster miRNAs in preovulatory dominant follicles that coordinately regulate the forkhead box protein O1 (FOXO1) gene. However, little is known about the role of this cluster in bovine granulosa cell function. We used an in vitro granulosa cell culture model to investigate this role. Granulosa cells aspirated from small growing follicles (3-5 mm in diameter) were cultured in Dulbecco modified Eagle medium/F-12 medium supplemented with fetal bovine serum and transfected with locked nucleic acid-based miRNA mimics, inhibitors, and corresponding negative controls. Overexpression of the miRNA cluster resulted in suppression of FOXO1 mRNA and protein, whereas inhibition of the cluster increased expression of FOXO1 mRNA. Overexpression also increased the relative rate of cell proliferation, whereas inhibition slowed it down. Similarly, the proportion of cells under G0/G1 arrest declined, whereas the ratio of cells in S phase increased in response to miR-183-96-182 overexpression. Selective knockdown of FOXO1 mRNA using anti-FOXO1 small interfering RNA increased the rate of granulosa cell proliferation, decreased the proportion of cells under G0/G1 arrest, and increased the proportion of cells in the S phase of cell cycle. Our data suggest that miR-183-96-182 cluster miRNAs promote proliferation and G1/S transition of bovine granulosa cells by coordinately targeting FOXO1, suggesting a critical role in granulosa cell function. MicroRNA-183-96-182 cluster regulates bovine granulosa cell function by targeting FOXO1 gene. © 2016 by the Society for the Study of Reproduction, Inc.

  3. Toll-Like Receptor Function in Acute Wounds.

    Science.gov (United States)

    Chen, Lin; DiPietro, Luisa A

    2017-10-01

    Significance: Inflammation is an integral part of immune response and supports optimal wound healing in adults. Inflammatory cells such as neutrophils, macrophages, dendritic cells, lymphocytes, and mast cells produce important cytokines, chemokines, and growth factors. These immune cells interact with keratinocytes, fibroblasts, and endothelial cells (ECs), as well as the extracellular matrix within a complicated network that promotes and regulates wound healing. Aberrant and persistent inflammation may result in delayed wound healing, scar formation, or chronic wounds. Targeting the molecules involved in the inflammatory response may have great potential therapeutic value. Recent Advances and Critical Issues: Toll-like receptors (TLRs) are pattern recognition receptors that recognize pathogen-associated molecular patterns from microbes or danger-associated molecular patterns from damaged cells. The discovery of TLRs sheds new light on the mechanism by which the inflammatory or innate immune response is initiated in wound healing. Convincing evidence now shows that multiple types of cells, including infiltrating or resident inflammatory cells, keratinocytes, fibroblasts, and ECs, express specific types of TLRs. Experimental reduction of certain TLRs or treatment of wounds with TLR ligands has been shown to affect wound healing. A better understanding of the involvement of TLRs in the innate immune response during skin wound healing may suggest novel strategies to improve the quality of tissue repair. Future Directions: Despite the indisputable role of TLRs in regulating the immune response in acute wound healing, the functions of TLRs that are relevant to human wound healing and chronic wounds are poorly understood.

  4. Proactive and Early Aggressive Wound Management: A Shift in Strategy Developed by a Consensus Panel Examining the Current Science, Prevention, and Management of Acute and Chronic Wounds.

    Science.gov (United States)

    Bohn, Gregory A; Schultz, Gregory S; Liden, Brock A; Desvigne, Michael N; Lullove, Eric J; Zilberman, Igor; Regan, Mary B; Ostler, Marta; Edwards, Karen; Arvanitis, Georgia M; Hartman, Jodi F

    2017-11-01

    Normal wound healing is accomplished through a series of well-coordinated, progressive events with overlapping phases. Chronic wounds are described as not progressing to healing or not being responsive to management in a timely manner. A consensus panel of multidisciplinary wound care professionals was assembled to (1) educate wound care practitioners by identifying key principles of the basic science of chronic wound pathophysiology, highlighting the impact of metalloproteinases and biofilms, as well as the role of the extracellular matrix; and (2) equip practitioners with a systematic strategy for the prevention and healing of acute injuries and chronic wounds based upon scientific evidence and the panel members' expertise. An algorithm is presented that represents a shift in strategy to proactive and early aggressive wound management. With proactive management, adjunct therapies are applied preemptively to acute injuries to reduce wound duration and risk of chronicity. For existing chronic wounds, early aggressive wound management is employed to break the pathophysiology cycle and drive wounds toward healing. Reducing bioburden through debridement and bioburden management and using collagen dressings to balance protease activity prior to the use of advanced modalities may enhance their effectiveness. This early aggressive wound management strategy is recommended for patients at high risk for chronic wound development at a minimum. In their own practices, the panel members apply this systematic strategy for all patients presenting with acute injuries or chronic wounds.

  5. Active wound dressing with artificial capillaries for temporary wound irrigation and skin cell supply.

    Science.gov (United States)

    Plettig, Jörn; Johnen, Christa M; Bräutigam, Kirsten; Zeilinger, Katrin; Borneman, Reinhard; Gerlach, Jörg C

    2012-04-01

    Medical treatment of burns and chronic wounds remains a challenge. We discussed a therapy concept that combines skin cell spray transplantation with a novel wound dressing based on artificial hollow fiber membrane capillaries. In skin cell-based therapy development, autologous skin progenitor cells are isolated from a healthy skin area and sprayed onto the wound. A medical device was introduced that uses perfused capillaries, known from clinical plasma separation, as a temporarily applied extracorporeal wound capillary bed. The functions of the dressing are comparable with those of dialysis; the capillaries, however, are applied externally onto the wound. Perfusion with a clinical peripheral nutrition and buffer solution can provide wound irrigation, wound debris removal, cell nutrition, pH regulation, and electrolyte balance while potentially serving to address delivery of regenerative factors and antibiosis. An innovative active skin wound dressing that provides cell support and stimulates regeneration by wound irrigation is discussed. © 2011, Copyright the Authors. Artificial Organs © 2011, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

  6. Soil Tillage Management Affects Maize Grain Yield by Regulating Spatial Distribution Coordination of Roots, Soil Moisture and Nitrogen Status.

    Science.gov (United States)

    Wang, Xinbing; Zhou, Baoyuan; Sun, Xuefang; Yue, Yang; Ma, Wei; Zhao, Ming

    2015-01-01

    The spatial distribution of the root system through the soil profile has an impact on moisture and nutrient uptake by plants, affecting growth and productivity. The spatial distribution of the roots, soil moisture, and fertility are affected by tillage practices. The combination of high soil density and the presence of a soil plow pan typically impede the growth of maize (Zea mays L.).We investigated the spatial distribution coordination of the root system, soil moisture, and N status in response to different soil tillage treatments (NT: no-tillage, RT: rotary-tillage, SS: subsoiling) and the subsequent impact on maize yield, and identify yield-increasing mechanisms and optimal soil tillage management practices. Field experiments were conducted on the Huang-Huai-Hai plain in China during 2011 and 2012. The SS and RT treatments significantly reduced soil bulk density in the top 0-20 cm layer of the soil profile, while SS significantly decreased soil bulk density in the 20-30 cm layer. Soil moisture in the 20-50 cm profile layer was significantly higher for the SS treatment compared to the RT and NT treatment. In the 0-20 cm topsoil layer, the NT treatment had higher soil moisture than the SS and RT treatments. Root length density of the SS treatment was significantly greater than density of the RT and NT treatments, as soil depth increased. Soil moisture was reduced in the soil profile where root concentration was high. SS had greater soil moisture depletion and a more concentration root system than RT and NT in deep soil. Our results suggest that the SS treatment improved the spatial distribution of root density, soil moisture and N states, thereby promoting the absorption of soil moisture and reducing N leaching via the root system in the 20-50 cm layer of the profile. Within the context of the SS treatment, a root architecture densely distributed deep into the soil profile, played a pivotal role in plants' ability to access nutrients and water. An optimal

  7. Coordinated regulation of transcriptional repression by the RBP2 H3K4 demethylase and Polycomb-Repressive Complex 2

    DEFF Research Database (Denmark)

    Pasini, Diego; Hansen, Klaus H; Christensen, Jesper

    2008-01-01

    Polycomb group (PcG) proteins regulate important cellular processes such as embryogenesis, cell proliferation, and stem cell self-renewal through the transcriptional repression of genes determining cell fate decisions. The Polycomb-Repressive Complex 2 (PRC2) is highly conserved during evolution......, and its intrinsic histone H3 Lys 27 (K27) trimethylation (me3) activity is essential for PcG-mediated transcriptional repression. Here, we show a functional interplay between the PRC2 complex and the H3K4me3 demethylase Rbp2 (Jarid1a) in mouse embryonic stem (ES) cells. By genome-wide location analysis we...... found that Rbp2 is associated with a large number of PcG target genes in mouse ES cells. We show that the PRC2 complex recruits Rbp2 to its target genes, and that this interaction is required for PRC2-mediated repressive activity during ES cell differentiation. Taken together, these results demonstrate...

  8. Single-stranded DNA binding by F TraI relaxase and helicase domains is coordinately regulated.

    Science.gov (United States)

    Dostál, Lubomír; Schildbach, Joel F

    2010-07-01

    Transfer of conjugative plasmids requires relaxases, proteins that cleave one plasmid strand sequence specifically. The F plasmid relaxase TraI (1,756 amino acids) is also a highly processive DNA helicase. The TraI relaxase activity is located within the N-terminal approximately 300 amino acids, while helicase motifs are located in the region comprising positions 990 to 1450. For efficient F transfer, the two activities must be physically linked. The two TraI activities are likely used in different stages of transfer; how the protein regulates the transition between activities is unknown. We examined TraI helicase single-stranded DNA (ssDNA) recognition to complement previous explorations of relaxase ssDNA binding. Here, we show that TraI helicase-associated ssDNA binding is independent of and located N-terminal to all helicase motifs. The helicase-associated site binds ssDNA oligonucleotides with nM-range equilibrium dissociation constants and some sequence specificity. Significantly, we observe an apparent strong negative cooperativity in ssDNA binding between relaxase and helicase-associated sites. We examined three TraI variants having 31-amino-acid insertions in or near the helicase-associated ssDNA binding site. B. A. Traxler and colleagues (J. Bacteriol. 188:6346-6353) showed that under certain conditions, these variants are released from a form of negative regulation, allowing them to facilitate transfer more efficiently than wild-type TraI. We find that these variants display both moderately reduced affinity for ssDNA by their helicase-associated binding sites and a significant reduction in the apparent negative cooperativity of binding, relative to wild-type TraI. These results suggest that the apparent negative cooperativity of binding to the two ssDNA binding sites of TraI serves a major regulatory function in F transfer.

  9. Role and regulation of coordinately expressed de novo purine biosynthetic enzymes PPAT and PAICS in lung cancer.

    Science.gov (United States)

    Goswami, Moloy T; Chen, Guoan; Chakravarthi, Balabhadrapatruni V S K; Pathi, Satya S; Anand, Sharath K; Carskadon, Shannon L; Giordano, Thomas J; Chinnaiyan, Arul M; Thomas, Dafydd G; Palanisamy, Nallasivam; Beer, David G; Varambally, Sooryanarayana

    2015-09-15

    Cancer cells exhibit altered metabolism including aerobic glycolysis that channels several glycolytic intermediates into de novo purine biosynthetic pathway. We discovered increased expression of phosphoribosyl amidotransferase (PPAT) and phosphoribosylaminoimidazole carboxylase, phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS) enzymes of de novo purine biosynthetic pathway in lung adenocarcinomas. Transcript analyses from next-generation RNA sequencing and gene expression profiling studies suggested that PPAT and PAICS can serve as prognostic biomarkers for aggressive lung adenocarcinoma. Immunohistochemical analysis of PAICS performed on tissue microarrays showed increased expression with disease progression and was significantly associated with poor prognosis. Through gene knockdown and over-expression studies we demonstrate that altering PPAT and PAICS expression modulates pyruvate kinase activity, cell proliferation and invasion. Furthermore we identified genomic amplification and aneuploidy of the divergently transcribed PPAT-PAICS genomic region in a subset of lung cancers. We also present evidence for regulation of both PPAT and PAICS and pyruvate kinase activity by L-glutamine, a co-substrate for PPAT. A glutamine antagonist, 6-Diazo-5-oxo-L-norleucine (DON) blocked glutamine mediated induction of PPAT and PAICS as well as reduced pyruvate kinase activity. In summary, this study reveals the regulatory mechanisms by which purine biosynthetic pathway enzymes PPAT and PAICS, and pyruvate kinase activity is increased and exposes an existing metabolic vulnerability in lung cancer cells that can be explored for pharmacological intervention.

  10. EHBP1L1 coordinates Rab8 and Bin1 to regulate apical-directed transport in polarized epithelial cells.

    Science.gov (United States)

    Nakajo, Atsuhiro; Yoshimura, Shin-ichiro; Togawa, Hiroko; Kunii, Masataka; Iwano, Tomohiko; Izumi, Ayaka; Noguchi, Yuria; Watanabe, Ayako; Goto, Ayako; Sato, Toshiro; Harada, Akihiro

    2016-02-01

    The highly conserved Rab guanosine triphosphatase (GTPase) Rab8 plays a role in exocytosis toward the polarized plasma membrane in eukaryotic cells. In murine Rab8-deficient small intestine cells, apical proteins are missorted into lysosomes. In this study, we identified a novel Rab8-interacting protein complex containing an EH domain-binding protein 1-like 1 (EHBP1L1), Bin1/amphiphysin II, and dynamin. Biochemical analyses showed that EHBP1L1 directly bound to GTP-loaded Rab8 and Bin1. The spatial dependency of these complexes at the endocytic recycling compartment (ERC) was demonstrated through overexpression and knockdown experiments. EHBP1L1- or Bin1-depleted or dynamin-inhibited small intestine organoids significantly accumulated apical membrane proteins but not basolateral membrane proteins in lysosomes. Furthermore, in EHBP1L1-deficient mice, small intestine cells displayed truncated and sparse microvilli, suggesting that EHBP1L1 maintains the apical plasma membrane by regulating apical transport. In summary, our data demonstrate that EHBP1L1 links Rab8 and the Bin1-dynamin complex, which generates membrane curvature and excises the vesicle at the ERC for apical transport. © 2016 Nakajo et al.

  11. Enabling children with Developmental Coordination Disorder to self-regulate through the use of Dynamic Performance Analysis: evidence from the CO-OP approach.

    Science.gov (United States)

    Hyland, M; Polatajko, H J

    2012-08-01

    Anecdotal evidence suggests that Dynamic Performance Analysis (DPA) is learned by children with Developmental Coordination Disorder (DCD) during Cognitive Orientation to Occupational Performance (CO-OP) intervention. DPA is a tool used by therapists during the CO-OP approach to identify performance breakdowns and strategies for skill acquisition. This suggests that the self-regulation difficulties experienced by these children are amenable to intervention. The purpose of this proof of principle study was to determine: if school-aged children with DCD carry out DPAs, if DPA use was positively affected by intervention, and whether CO-OP had a larger effect on DPA use. Previously recorded videos of 13 children with DCD undergoing CO-OP, contemporary treatment or task-specific training were analyzed for evidence of DPA use. It was found that children in all three groups used simple DPAs before intervention; those receiving CO-OP intervention dramatically increased the number and quality of DPAs and could spontaneously apply it to the performance of another child. These findings indicate that, despite issues of self-regulation, children with DCD do self-monitor performance. More importantly, this ability can improve with CO-OP intervention as it guides the discovery of self-identified performance solutions, thereby enabling skill acquisition, generalization and transfer. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Coordinated transcriptional regulation of two key genes in the lignin branch pathway - CAD and CCR - is mediated through MYB- binding sites

    Directory of Open Access Journals (Sweden)

    Chaubet-Gigot Nicole

    2010-06-01

    Full Text Available Abstract Background Cinnamoyl CoA reductase (CCR and cinnamyl alcohol dehydrogenase (CAD catalyze the final steps in the biosynthesis of monolignols, the monomeric units of the phenolic lignin polymers which confer rigidity, imperviousness and resistance to biodegradation to cell walls. We have previously shown that the Eucalyptus gunnii CCR and CAD2 promoters direct similar expression patterns in vascular tissues suggesting that monolignol production is controlled, at least in part, by the coordinated transcriptional regulation of these two genes. Although consensus motifs for MYB transcription factors occur in most gene promoters of the whole phenylpropanoid pathway, functional evidence for their contribution to promoter activity has only been demonstrated for a few of them. Here, in the lignin-specific branch, we studied the functional role of MYB elements as well as other cis-elements identified in the regulatory regions of EgCAD2 and EgCCR promoters, in the transcriptional activity of these gene promoters. Results By using promoter deletion analysis and in vivo footprinting, we identified an 80 bp regulatory region in the Eucalyptus gunnii EgCAD2 promoter that contains two MYB elements, each arranged in a distinct module with newly identified cis-elements. A directed mutagenesis approach was used to introduce block mutations in all putative cis-elements of the EgCAD2 promoter and in those of the 50 bp regulatory region previously delineated in the EgCCR promoter. We showed that the conserved MYB elements in EgCAD2 and EgCCR promoters are crucial both for the formation of DNA-protein complexes in EMSA experiments and for the transcriptional activation of EgCAD2 and EgCCR promoters in vascular tissues in planta. In addition, a new regulatory cis-element that modulates the balance between two DNA-protein complexes in vitro was found to be important for EgCAD2 expression in the cambial zone. Conclusions Our assignment of functional roles to the

  13. Enhanced photosynthetic capacity increases nitrogen metabolism through the coordinated regulation of carbon and nitrogen assimilation in Arabidopsis thaliana.

    Science.gov (United States)

    Otori, Kumi; Tanabe, Noriaki; Maruyama, Toshiki; Sato, Shigeru; Yanagisawa, Shuichi; Tamoi, Masahiro; Shigeoka, Shigeru

    2017-09-01

    Plant growth and productivity depend on interactions between the metabolism of carbon and nitrogen. The sensing ability of internal carbon and nitrogen metabolites (the C/N balance) enables plants to regulate metabolism and development. In order to investigate the effects of an enhanced photosynthetic capacity on the metabolism of carbon and nitrogen in photosynthetically active tissus (source leaves), we herein generated transgenic Arabidopsis thaliana plants (ApFS) that expressed cyanobacterial fructose-1,6-/sedoheptulose-1,7-bisphosphatase in their chloroplasts. The phenotype of ApFS plants was indistinguishable from that of wild-type plants at the immature stage. However, as plants matured, the growth of ApFS plants was superior to that of wild-type plants. Starch levels were higher in ApFS plants than in wild-type plants at 2 and 5 weeks. Sucrose levels were also higher in ApFS plants than in wild-type plants, but only at 5 weeks. On the other hand, the contents of various free amino acids were lower in ApFS plants than in wild-type plants at 2 weeks, but were similar at 5 weeks. The total C/N ratio was the same in ApFS plants and wild-type plants, whereas nitrite levels increased in parallel with elevations in nitrate reductase activity at 5 weeks in ApFS plants. These results suggest that increases in the contents of photosynthetic intermediates at the early growth stage caused a temporary imbalance in the free-C/free-N ratio and, thus, the feedback inhibition of the expression of genes involved in the Calvin cycle and induction of the expression of those involved in nitrogen metabolism due to supply deficient free amino acids for maintenance of the C/N balance in source leaves of ApFS plants.

  14. Expression of coordinately regulated defence response genes and analysis of their role in disease resistance in Medicago truncatula.

    Science.gov (United States)

    Samac, Deborah A; Peñuela, Silvia; Schnurr, Judy A; Hunt, E Nicole; Foster-Hartnett, Dawn; Vandenbosch, Kathryn A; Gantt, J Stephen

    2011-10-01

    Microarray technology was used to identify the genes associated with disease defence responses in the model legume Medicago truncatula. Transcript profiles from M. truncatula cv. Jemalong genotype A17 leaves inoculated with Colletotrichum trifolii and Erysiphe pisi and roots infected with Phytophthora medicaginis were compared to identify the genes expressed in response to all three pathogens and genes unique to an interaction. The A17 genotype is resistant to C. trifolii and E. pisi, exhibiting a hypersensitive response after inoculation, and is moderately susceptible to P. medicaginis. Among the most strongly up-regulated genes in all three interactions were those encoding a hevein-like protein, thaumatin-like protein (TLP) and members of the pathogenesis response (PR)10 family. Transcripts of genes for enzymes in the phenylpropanoid pathway leading to the production of isoflavonoid phytoalexins increased dramatically in response to inoculation with the foliar pathogens. In P. medicaginis-inoculated roots, transcripts of genes in the phenylpropanoid pathway peaked at 5 days post-inoculation, when symptoms became visible. Transcript accumulation of three PR10 family members, a TLP and chalcone synthase (CHS) was assessed in M. truncatula genotype R108 plants. The R108 plants are resistant to C. trifolii and moderately susceptible to E. pisi and P. medicaginis. Transcript accumulation paralleled the stages of pathogen development. To evaluate the role of a TLP, a PR10 family member and CHS in disease resistance, transgenic R108 plants containing interfering RNA (RNAi) constructs were produced. Reduced expression of PR10 and TLP had no effect on the disease phenotype, whereas reduced expression of CHS resulted in increased susceptibility to necrotrophic pathogens. MOLECULAR PLANT PATHOLOGY © 2011 BSPP AND BLACKWELL PUBLISHING LTD. NO CLAIM TO ORIGINAL US GOVERNMENT WORKS.

  15. Meta-analysis of breast cancer microarray studies in conjunction with conserved cis-elements suggest patterns for coordinate regulation

    Directory of Open Access Journals (Sweden)

    Lundberg Cathryn

    2008-01-01

    Full Text Available Abstract Background Gene expression measurements from breast cancer (BrCa tumors are established clinical predictive tools to identify tumor subtypes, identify patients showing poor/good prognosis, and identify patients likely to have disease recurrence. However, diverse breast cancer datasets in conjunction with diagnostic clinical arrays show little overlap in the sets of genes identified. One approach to identify a set of consistently dysregulated candidate genes in these tumors is to employ meta-analysis of multiple independent microarray datasets. This allows one to compare expression data from a diverse collection of breast tumor array datasets generated on either cDNA or oligonucleotide arrays. Results We gathered expression data from 9 published microarray studies examining estrogen receptor positive (ER+ and estrogen receptor negative (ER- BrCa tumor cases from the Oncomine database. We performed a meta-analysis and identified genes that were universally up or down regulated with respect to ER+ versus ER- tumor status. We surveyed both the proximal promoter and 3' untranslated regions (3'UTR of our top-ranking genes in each expression group to test whether common sequence elements may contribute to the observed expression patterns. Utilizing a combination of known transcription factor binding sites (TFBS, evolutionarily conserved mammalian promoter and 3'UTR motifs, and microRNA (miRNA seed sequences, we identified numerous motifs that were disproportionately represented between the two gene classes suggesting a common regulatory network for the observed gene expression patterns. Conclusion Some of the genes we identified distinguish key transcripts previously seen in array studies, while others are newly defined. Many of the genes identified as overexpressed in ER- tumors were previously identified as expression markers for neoplastic transformation in multiple human cancers. Moreover, our motif analysis identified a collection of

  16. Glucocorticoid coordinate regulation of type I procollagen gene expression and procollagen DNA-binding proteins in chick skin fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Cockayne, D.; Cutroneo, K.R.

    1988-04-19

    Nuclei were isolated from control and dexamethasone-treated (2 h) embryonic chick skin fibroblasts and transcribed in vitro. Nuclei isolated from dexamethasone-treated fibroblasts transcribed less pro..cap alpha..1(I) and pro..cap alpha..2(I) mRNAs but not ..beta..-actin mRNA. Fibroblasts receiving dexamethasone and (5,6-/sup 3/H)uridine also demonstrated decreased synthesis of nuclear type I procollagen mRNAs but not ..beta..-actin mRNA. In fibroblasts treated with cycloheximide the newly synthesized nuclear type I procollagen mRNA species were markedly decreased. An enhanced inhibitory effect was observed when fibroblasts were treated with cycloheximide plus dexamethasone. Since the studies above demonstrate that active protein synthesis is required to maintain the constitutive expression of the type I procollagen genes, the authors determined if glucocorticoids regulate DNA-binding proteins with sequence specificity for the ..cap alpha..2(I) procollagen gene. Nuclear protein blots were probed with the /sup 32/P-end-labeled pBR322 vector DNA and /sup 32/P-end-labeled ..cap alpha..2(I) procollagen promoter containing DNA. Nonhistone proteins remained bound to labeled DNA at stringency washes of 0.05 and 0.1 M NaCl. As the ionic strength was increased to 0.2 and 0.3 M NaCl, the nonhistone-protein DNA binding was preferentially lost. Only the low molecular weight proteins remained bound to labeled DNA at the highest ionic strength, indicating nonspecific binding of these nuclear proteins. Dexamethasone treatment resulted in an increase of binding of nonhistone proteins to vector- and promoter-labeled DNAs over that observed in control fibroblasts at stringency washes of 0.05 and 0.1 M NaCl and to a lesser extent at 0.2 M NaCl. The binding specificities of nonhistone proteins for the ..cap alpha..2(I) procollagen promoter containing DNA were calculated.

  17. Wound care in horses.

    Science.gov (United States)

    Caston, Stephanie S

    2012-04-01

    Care of equine wounds in the field can be a challenging endeavor. Many times, wound care is complicated by chronicity or by prior inappropriate care in addition to the great degree of tissue trauma that occurred when the horse was wounded. Recognizing involvement of synovial structures, loss of skin, and damage to bone are critical in the initial examination of wounds and will guide future care. Education of clients is also important in that preparing them for possible outcomes during healing may help improve compliance and proper treatment of wound. Owners and trainers often perform much of the daily care and monitoring of equine wounds and thus can greatly assist or impede the progress. Bandaging is important to management of equine wounds-especially on the limbs-and is sometimes overlooked because of its labor-intensive nature and the desire for a spray, ointment, or salve that will heal the wound. The practitioner that improves and utilizes his or her understanding of the wound-healing process in concert with his or her knowledge of local anatomy will be the one who is best equipped to care for wounds in ambulatory practice.

  18. Proper actin ring formation and septum constriction requires coordinated regulation of SIN and MOR pathways through the germinal centre kinase MST-1.

    Science.gov (United States)

    Heilig, Yvonne; Dettmann, Anne; Mouriño-Pérez, Rosa R; Schmitt, Kerstin; Valerius, Oliver; Seiler, Stephan

    2014-04-01

    Nuclear DBF2p-related (NDR) kinases constitute a functionally conserved protein family of eukaryotic regulators that control cell division and polarity. In fungi, they function as effector kinases of the morphogenesis (MOR) and septation initiation (SIN) networks and are activated by pathway-specific germinal centre (GC) kinases. We characterized a third GC kinase, MST-1, that connects both kinase cascades. Genetic and biochemical interactions with SIN components and life cell imaging identify MST-1 as SIN-associated kinase that functions in parallel with the GC kinase SID-1 to activate the SIN-effector kinase DBF-2. SID-1 and MST-1 are both regulated by the upstream SIN kinase CDC-7, yet in an opposite manner. Aberrant cortical actomyosin rings are formed in Δmst-1, which resulted in mis-positioned septa and irregular spirals, indicating that MST-1-dependent regulation of the SIN is required for proper formation and constriction of the septal actomyosin ring. However, MST-1 also interacts with several components of the MOR network and modulates MOR activity at multiple levels. MST-1 functions as promiscuous enzyme and also activates the MOR effector kinase COT-1 through hydrophobic motif phosphorylation. In addition, MST-1 physically interacts with the MOR kinase POD-6, and dimerization of both proteins inactivates the GC kinase hetero-complex. These data specify an antagonistic relationship between the SIN and MOR during septum formation in the filamentous ascomycete model Neurospora crassa that is, at least in part, coordinated through the GC kinase MST-1. The similarity of the SIN and MOR pathways to the animal Hippo and Ndr pathways, respectively, suggests that intensive cross-communication between distinct NDR kinase modules may also be relevant for the homologous NDR kinases of higher eukaryotes.

  19. Diabetes and Wound Angiogenesis

    Directory of Open Access Journals (Sweden)

    Uzoagu A. Okonkwo

    2017-07-01

    Full Text Available Diabetes Mellitus Type II (DM2 is a growing international health concern with no end in sight. Complications of DM2 involve a myriad of comorbidities including the serious complications of poor wound healing, chronic ulceration, and resultant limb amputation. In skin wound healing, which has definite, orderly phases, diabetes leads to improper function at all stages. While the etiology of chronic, non-healing diabetic wounds is multi-faceted, the progression to a non-healing phenotype is closely linked to poor vascular networks. This review focuses on diabetic wound healing, paying special attention to the aberrations that have been described in the proliferative, remodeling, and maturation phases of wound angiogenesis. Additionally, this review considers therapeutics that may offer promise to better wound healing outcomes.

  20. Biofilms in wounds

    DEFF Research Database (Denmark)

    Cooper, R A; Bjarnsholt, Thomas; Alhede, M

    2014-01-01

    Following confirmation of the presence of biofilms in chronic wounds, the term biofilm became a buzzword within the wound healing community. For more than a century pathogens have been successfully isolated and identified from wound specimens using techniques that were devised in the nineteenth...... extracellular polymeric substances (EPS). Cells within such aggregations (or biofilms) display varying physiological and metabolic properties that are distinct from those of planktonic cells, and which contribute to their persistence. There are many factors that influence healing in wounds and the discovery...... of biofilms in chronic wounds has provided new insight into the reasons why. Increased tolerance of biofilms to antimicrobial agents explains the limited efficacy of antimicrobial agents in chronic wounds and illustrates the need to develop new management strategies. This review aims to explain the nature...

  1. Factors Affecting Wound Healing

    Science.gov (United States)

    Guo, S.; DiPietro, L.A.

    2010-01-01

    Wound healing, as a normal biological process in the human body, is achieved through four precisely and highly programmed phases: hemostasis, inflammation, proliferation, and remodeling. For a wound to heal successfully, all four phases must occur in the proper sequence and time frame. Many factors can interfere with one or more phases of this process, thus causing improper or impaired wound healing. This article reviews the recent literature on the most significant factors that affect cutaneous wound healing and the potential cellular and/or molecular mechanisms involved. The factors discussed include oxygenation, infection, age and sex hormones, stress, diabetes, obesity, medications, alcoholism, smoking, and nutrition. A better understanding of the influence of these factors on repair may lead to therapeutics that improve wound healing and resolve impaired wounds. PMID:20139336

  2. Transcriptome analysis at four developmental stages of grape berry (Vitis vinifera cv. Shiraz provides insights into regulated and coordinated gene expression

    Directory of Open Access Journals (Sweden)

    Sweetman Crystal

    2012-12-01

    Full Text Available Abstract Background Vitis vinifera berry development is characterised by an initial phase where the fruit is small, hard and acidic, followed by a lag phase known as veraison. In the final phase, berries become larger, softer and sweeter and accumulate an array of organoleptic compounds. Since the physiological and biochemical makeup of grape berries at harvest has a profound impact on the characteristics of wine, there is great interest in characterising the molecular and biophysical changes that occur from flowering through veraison and ripening, including the coordination and temporal regulation of metabolic gene pathways. Advances in deep-sequencing technologies, combined with the availability of increasingly accurate V. vinifera genomic and transcriptomic data, have enabled us to carry out RNA-transcript expression analysis on a global scale at key points during berry development. Results A total of 162 million 100-base pair reads were generated from pooled Vitis vinifera (cv. Shiraz berries sampled at 3-weeks post-anthesis, 10- and 11-weeks post-anthesis (corresponding to early and late veraison and at 17-weeks post-anthesis (harvest. Mapping reads from each developmental stage (36-45 million onto the NCBI RefSeq transcriptome of 23,720 V. vinifera mRNAs revealed that at least 75% of these transcripts were detected in each sample. RNA-Seq analysis uncovered 4,185 transcripts that were significantly upregulated at a single developmental stage, including 161 transcription factors. Clustering transcripts according to distinct patterns of transcription revealed coordination in metabolic pathways such as organic acid, stilbene and terpenoid metabolism. From the phenylpropanoid/stilbene biosynthetic pathway at least 46 transcripts were upregulated in ripe berries when compared to veraison and immature berries, and 12 terpene synthases were predominantly detected only in a single sample. Quantitative real-time PCR was used to validate the

  3. Transcriptome analysis at four developmental stages of grape berry (Vitis vinifera cv. Shiraz) provides insights into regulated and coordinated gene expression.

    Science.gov (United States)

    Sweetman, Crystal; Wong, Darren Cj; Ford, Christopher M; Drew, Damian P

    2012-12-11

    Vitis vinifera berry development is characterised by an initial phase where the fruit is small, hard and acidic, followed by a lag phase known as veraison. In the final phase, berries become larger, softer and sweeter and accumulate an array of organoleptic compounds. Since the physiological and biochemical makeup of grape berries at harvest has a profound impact on the characteristics of wine, there is great interest in characterising the molecular and biophysical changes that occur from flowering through veraison and ripening, including the coordination and temporal regulation of metabolic gene pathways. Advances in deep-sequencing technologies, combined with the availability of increasingly accurate V. vinifera genomic and transcriptomic data, have enabled us to carry out RNA-transcript expression analysis on a global scale at key points during berry development. A total of 162 million 100-base pair reads were generated from pooled Vitis vinifera (cv. Shiraz) berries sampled at 3-weeks post-anthesis, 10- and 11-weeks post-anthesis (corresponding to early and late veraison) and at 17-weeks post-anthesis (harvest). Mapping reads from each developmental stage (36-45 million) onto the NCBI RefSeq transcriptome of 23,720 V. vinifera mRNAs revealed that at least 75% of these transcripts were detected in each sample. RNA-Seq analysis uncovered 4,185 transcripts that were significantly upregulated at a single developmental stage, including 161 transcription factors. Clustering transcripts according to distinct patterns of transcription revealed coordination in metabolic pathways such as organic acid, stilbene and terpenoid metabolism. From the phenylpropanoid/stilbene biosynthetic pathway at least 46 transcripts were upregulated in ripe berries when compared to veraison and immature berries, and 12 terpene synthases were predominantly detected only in a single sample. Quantitative real-time PCR was used to validate the expression pattern of 12 differentially expressed

  4. Understanding the Host Inflammatory Response to Wound Infection: An In Vivo Study of Klebsiella pneumoniae in a Rabbit Ear Wound Model

    Science.gov (United States)

    2012-01-01

    punched out and immediately snap -frozen in liquid nitrogen. Wound samples were homogenized using a Mini-bead beater-8 equipment (Biospec Products, Inc...regulation of wound healing. Int J Low Extrem Wounds 2004; 3: 201–8. 13. Bernard JJ, Gallo RL. Protecting the boundary: the sentinel role of host defense

  5. Anterior gradient 2 is induced in cutaneous wound and promotes wound healing through its adhesion domain.

    Science.gov (United States)

    Zhu, Qi; Mangukiya, Hitesh Bhagavanbhai; Mashausi, Dhahiri Saidi; Guo, Hao; Negi, Hema; Merugu, Siva Bharath; Wu, Zhenghua; Li, Dawei

    2017-09-01

    Anterior gradient 2 (AGR2), a member of protein disulfide isomerase (PDI) family, is both located in cytoplasm and secreted into extracellular matrix. The orthologs of AGR2 have been linked to limb regeneration in newt and wound healing in zebrafish. In mammals, AGR2 influences multiple cell signaling pathways in tumor formation and in normal cell functions related to new tissue formation like angiogenesis. However, the function of AGR2 in mammalian wound healing remains unknown. This study aimed to investigate AGR2 expression and its function during skin wound healing and the possible application of external AGR2 in cutaneous wound to accelerate the healing process. Our results showed that AGR2 expression was induced in the migrating epidermal tongue and hyperplastic epidermis after skin excision. Topical application of recombinant AGR2 significantly accelerated wound-healing process by increasing the migration of keratinocytes (Kera.) and the recruitment of fibroblasts (Fibro.) near the wounded area. External AGR2 also promoted the migration of Kera. and Fibro. in vitro in a dose-dependent manner. The adhesion domain of AGR2 was required for the formation of focal adhesions in migrating Fibro., leading to the directional migration along AGR2 gradient. These results indicate that recombinant AGR2 accelerates skin wound healing through regulation of Kera. and Fibro. migration, thus demonstrating its potential utility as an alternative strategy of the therapeutics to accelerate the healing of acute or chronic skin wounds. © 2017 Federation of European Biochemical Societies.

  6. Wound Assessment: Made Easy

    OpenAIRE

    Ousey, Karen; Cook, Leanne

    2012-01-01

    A structured approach to wound assessment is required to maintain a good standard of care. This involves a thorough patient assessment, which should be carried out by skilled and competent practitioners, adhering to local and national guidelines (Harding et al, 2008). Inappropriate or inaccurate assessment can lead to delayed wound healing, pain, increased risk of infection, inappropriate use of wound dressings and a reduction in the quality of life for patients.

  7. Innovation and wound healing.

    Science.gov (United States)

    Harding, Keith

    2015-04-01

    Innovation in medicine requires unique partnerships between academic research, biotech or pharmaceutical companies, and health-care providers. While innovation in medicine has greatly increased over the past 100 years, innovation in wound care has been slow, despite the fact that chronic wounds are a global health challenge where there is a need for technical, process and social innovation. While novel partnerships between research and the health-care system have been created, we still have much to learn about wound care and the wound-healing processes.

  8. Telemedicine for wound management

    Directory of Open Access Journals (Sweden)

    Ravi K Chittoria

    2012-01-01

    Full Text Available The escalating physiological, psychological, social and financial burdens of wounds and wound care on patients, families and society demand the immediate attention of the health care sector. Many forces are affecting the changes in health care provision for patients with chronic wounds, including managed care, the limited number of wound care therapists, an increasingly ageing and disabled population, regulatory and malpractice issues, and compromised care. The physician is also faced with a number of difficult issues when caring for chronic wound patients because their conditions are time consuming and high risk, represent an unprofitable part of care practice and raise issues of liability. Telemedicine enhances communication with the surgical wound care specialist. Digital image for skin lesions is a safe, accurate and cost-effective referral pathway. The two basic modes of telemedicine applications, store and forward (asynchronous transfer and real-time transmission (synchronous transfer, e.g. video conference, are utilized in the wound care setting. Telemedicine technology in the hands of an experienced physician can streamline management of a problem wound. Although there is always an element of anxiety related to technical change, the evolution of wound care telemedicine technology has demonstrated a predictable maturation process.

  9. Inflammation in Chronic Wounds.

    Science.gov (United States)

    Zhao, Ruilong; Liang, Helena; Clarke, Elizabeth; Jackson, Christopher; Xue, Meilang

    2016-12-11

    Non-healing chronic wounds present a major biological, psychological, social, and financial burden on both individual patients and the broader health system. Pathologically extensive inflammation plays a major role in the disruption of the normal healing cascade. The causes of chronic wounds (venous, arterial, pressure, and diabetic ulcers) can be examined through a juxtaposition of normal healing and the rogue inflammatory response created by the common components within chronic wounds (ageing, hypoxia, ischaemia-reperfusion injury, and bacterial colonisation). Wound bed care through debridement, dressings, and antibiotics currently form the basic mode of treatment. Despite recent setbacks, pharmaceutical adjuncts form an interesting area of research.

  10. Synaptic Plasticity and NO-cGMP-PKG Signaling Coordinately Regulate ERK-Driven Gene Expression in the Lateral Amygdala and in the Auditory Thalamus Following Pavlovian Fear Conditioning

    Science.gov (United States)

    Ota, Kristie T.; Monsey, Melissa S.; Wu, Melissa S.; Young, Grace J.; Schafe, Glenn E.

    2010-01-01

    We have recently hypothesized that NO-cGMP-PKG signaling in the lateral nucleus of the amygdala (LA) during auditory fear conditioning coordinately regulates ERK-driven transcriptional changes in both auditory thalamic (MGm/PIN) and LA neurons that serve to promote pre- and postsynaptic alterations at thalamo-LA synapses, respectively. In the…

  11. Dimensions of Organizational Coordination

    DEFF Research Database (Denmark)

    Jensen, Andreas Schmidt; Aldewereld, Huib; Dignum, Virginia

    2013-01-01

    be supported to include organizational objectives and constraints into their reasoning processes by considering two alternatives: agent reasoning and middleware regulation. We show how agents can use an organizational specification to achieve organizational objectives by delegating and coordinating...... their activities with other agents in the society, using the GOAL agent programming language and the OperA organizational model....

  12. Vinculin, VASP, and profilin are coordinately regulated during actin remodeling in epithelial cells, which requires de novo protein synthesis and protein kinase signal transduction pathways.

    Science.gov (United States)

    Quinlan, Margaret P

    2004-08-01

    Transformation progression of epithelial cells involves alterations in their morphology, polarity, and adhesive characteristics, all of which are associated with the loss and/or reorganization of actin structures. To identify the underlying mechanism of formation of the adhesion-dependent, circumferential actin network, the expression and localization of the actin binding and regulating proteins (ABPs), vinculin, VASP, and profilin were evaluated. Experimental depolarization of epithelial cells results in the loss of normal F-actin structures and the transient upregulation of vinculin, VASP, and profilin. This response is due to the loss of cell-cell, and not cell-substrate interactions, since cells that no longer express focal adhesions or stress fibers are still sensitive to changes in adhesion and manifest this in the altered profile of expression of these ABPs. Transient upregulation is dependent upon de novo protein synthesis, and protein kinase-, but not phosphatase-sensitive signal transduction pathway(s). Inhibition of the synthesis of these proteins is accompanied by dephosphorylation of the ribosomal S6 protein, but does not involve inhibition of the PI3-kinase-Akt-mTOR pathway. Constitutive expression of VASP results in altered cell morphology and adhesion and F-actin and vinculin structures. V12rac1 expressing epithelial cells are constitutively nonadhesive, malignantly transformed, and constitutively express high levels of these ABPs, with altered subcellular localizations. Transformation suppression is accompanied by the restoration of normal levels of the three ABPs, actin structures, adhesion, and epithelial morphology. Thus, vinculin, VASP, and profilin are coordinately regulated by signal transduction pathways that effect a translational response. Additionally, their expression profile maybe indicative of the adhesion and transformation status of epithelial cells. Copyright 2004 Wiley-Liss, Inc.

  13. The Semaphorin 4D-RhoA-Akt Signal Cascade Regulates Enamel Matrix Secretion in Coordination With Cell Polarization During Ameloblast Differentiation.

    Science.gov (United States)

    Otsu, Keishi; Ida-Yonemochi, Hiroko; Fujiwara, Naoki; Harada, Hidemitsu

    2016-11-01

    During tooth development, oral epithelial cells differentiate into ameloblasts in order to form the most mineralized tissue in the vertebrate body: enamel. During this process, ameloblasts directionally secrete enamel matrix proteins and morphologically change from low columnar cells to polarized tall columnar cells, both of which are essential for the proper formation of enamel. In this study, we elucidated the molecular mechanism that integrates ameloblast function and morphology. Immunohistochemistry revealed that the restricted expression of semaphorin 4D (Sema4D) and RhoA activation status are closely associated with ameloblast differentiation in mouse incisors. In addition, in vitro gain-of-function and loss-of-function experiments demonstrated that Sema4D acts upstream of RhoA to regulate cell polarity and amelogenin expression via the Plexin B1/Leukemia-associated RhoGEF (LARG) complex during ameloblast differentiation. Experiments in transgenic mice demonstrated that expression of a dominant-negative form of RhoA in dental epithelium hindered ameloblast differentiation and subsequent enamel formation, as well as perturbing the establishment of polarized cell morphology and vectorial amelogenin expression. Finally, we showed that spatially restricted Akt mediates between Sema4D-RhoA signaling and these downstream cellular events. Collectively, our results reveal a novel signaling network, the Sema4D-RhoA-Akt signal cascade, that coordinates cellular function and morphology and highlights the importance of specific spatiotemporally restricted components of a signaling pathway in the regulation of ameloblast differentiation. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.

  14. Coordinate amplification of metallothionein I and II genes in cadmium-resistant Chinese hamster cells: implications for mechanisms regulating metallothionein gene expression

    Energy Technology Data Exchange (ETDEWEB)

    Crawford, B.D.; Enger, M.D.; Griffith, B.B.; Griffith, J.K.; Hanners, J.L.; Longmire, J.L.; Munk, A.C.; Stallings, R.L.; Tesmer, J.G.; Walters, R.A.; Hildebrand, C.E.

    1985-02-01

    The authors describe here the derivation, characterization, and use of clonal cadmium-resistance (Cd/sup r) strains of the Chinese hamster cell line CHO which differ in their metallothionein (MT) induction capacity. By nondenaturing polyacrylaminde gel electrophoresis, the authors showed that the stable Cd/sup r/ phenotype is correlated with the augmented expression of both isometallothioneins (MTI and MTII). In cells resistant to concentrations of CdCl2 exceeding 20 M, coordinate amplifications of genes encoding both isometallothioneins was demonstrated by using cDNA MT-coding sequence probes and probes specific for 3'-noncoding regions of Chinese hamster MTI and MTII genes. Molecular and in situ hybridization analyses supported close linkage of Chinese hamster MTI and MTII genes, which the authors have mapped previously to Chinese hamster chromosome 3. This suggests the existence of a functionally related MT gene cluster in this species. Amplified Cd/sup r/ variants expressing abundant MT and their corresponding Cd/sup s/ parental CHO cells should be useful for future studies directed toward elucidating the mechanisms that regulate expressions of the isometallothioneins. 59 references, 8 figures.

  15. Activity of the Bacillus thuringiensis NprR-NprX cell-cell communication system is co-ordinated to the physiological stage through a complex transcriptional regulation.

    Science.gov (United States)

    Dubois, Thomas; Perchat, Stéphane; Verplaetse, Emilie; Gominet, Myriam; Lemy, Christelle; Aumont-Nicaise, Magali; Grenha, Rosa; Nessler, Sylvie; Lereclus, Didier

    2013-04-01

    NprR is a quorum sensor of the RNPP family found in bacteria of the Bacillus cereus group. In association with its cognate peptide NprX, NprR controls the expression of genes essential for survival and sporulation of Bacillus thuringiensis during its necrotrophic development in insects. Here, we report that the nprR-nprX genes are not autoregulated and are co-transcribed from a σ(A) -dependent promoter (PA ) located upstream from nprR. The transcription from PA starts at the onset of the stationary phase and is controlled by two transcriptional regulators: CodY and PlcR. The nutritional repressor CodY represses nprR-nprX transcription during the exponential growth phase and the quorum sensor PlcR activates nprR-nprX transcription at the onset of stationary phase. We show that nprX is also transcribed independently of nprR from two promoters, PH and PE , dependent on the sporulation-specific sigma factors, σ(H) and σ(E) respectively. Both promoters ensure nprX transcription during late stationary phase while transcription from PA has decreased. These results show that the activity of the NprR-NprX quorum sensing system is tightly co-ordinated to the physiological stage throughout the developmental process of the Bacillus. © 2013 Blackwell Publishing Ltd.

  16. The effect of surgical wounding on tumour development

    NARCIS (Netherlands)

    Hofer, SOP; Molema, G; Hermens, RAEC; Wanebo, HJ; Reichner, JS; Hoekstra, HJ

    For more than a century, a role for wound healing in the outgrowth of tumours has been implied based on observations in both experimental and clinical studies. Wound healing can be divided into stages of inflammatory, proliferative, repair and remodelling processes. Through proper regulation of

  17. Sugar for wounds.

    Science.gov (United States)

    Topham, J

    2000-07-01

    Sugar in its pure form, or incorporated into a paste containing an adhesive hydropolymer (gum), is a non-toxic treatment for a variety of wounds. Not only does it provide a suitable clean environment for angiogenesis to take place, but it will debride the wound surface and reduce odour. The presence of an adhesive hydropolymer seems to prevent hypergranulation, scarring and contraction.

  18. Surgical wound infection - treatment

    Science.gov (United States)

    ... page: //medlineplus.gov/ency/article/007645.htm Surgical wound infection - treatment To use the sharing features on this page, ... the organ and space where you had surgery Treatment Antibiotics are used to treat most wound infections. Sometimes, you also may need surgery to ...

  19. Kaposi's Sarcoma-Associated Herpesvirus K8 Is an RNA Binding Protein That Regulates Viral DNA Replication in Coordination with a Noncoding RNA.

    Science.gov (United States)

    Liu, Dongcheng; Wang, Yan; Yuan, Yan

    2018-01-10

    KSHV lytic replication and constant primary infection of fresh cells are crucial for viral tumorigenicity. Virus-encoded b-Zip family protein K8 plays an important role in viral DNA replication in both viral reactivation and de novo infection. The mechanism underlying the functional role of K8 in the viral life cycle is elusive. Here we report that K8 is a RNA binding protein, which also associates with many proteins including other RNA binding proteins. Many K8-involved protein-protein interactions are mediated by RNA. Using a crosslinking and immunoprecipitation (CLIP) procedure combined with high-throughput sequencing, RNAs that are associated with K8 in BCBL-1 cells were identified, that include both viral (PAN, T1.4, T0.7 and etc.) and cellular (MALAT-1, MRP, 7SK and etc.) RNAs. An RNA-binding motif in K8 was defined, and mutation of the motif abolished the ability of K8 binding to many noncoding RNAs as well as viral DNA replication during de novo infection, suggesting that the K8 functions in viral replication are carried out through RNA association. The function of K8 and associated T1.4 RNA was investigated in details and results showed that T1.4 mediates the binding of K8 with ori-Lyt DNA. T1.4-K8 complex physically bound to KSHV ori-Lyt DNA and recruited other proteins and cofactors to assemble replication complex. Depletion of T1.4 abolished the DNA replication in primary infection. These findings provide mechanistic insights into the role of K8 in coordination with T1.4 RNA in regulating KSHV DNA replication during de novo infection.ImportanceGenome wide analyses of the mammalian transcriptome revealed that a large proportion of sequence previously annotated as noncoding region are actually transcribed and give rise to stable RNAs. Emergence of a large number of noncoding RNAs suggests that functional RNA-protein complexes exampled by ribosome or spliceosome are not ancient relics of the last riboorganism but would be well adapted for regulatory role

  20. Protein matrices for wound dressings =

    Science.gov (United States)

    Vasconcelos, Andreia Joana Costa

    indicated that these peptides are competitive inhibitors for HNE and PPE and, that the inhibitory potency can be regulated by the introduced modifications. Additionally, these peptides showed no toxicity with human skin fibroblasts and, were also effective in reducing the HNE activity found in a human chronic wound exudate, which allow them to be applied to those wounds. The motivation for this thesis was to combine the excellent properties of silk fibroin with other proteins. Blending allows modulating the physical-chemical properties of the resulting materials such as mechanical strength, swelling, morphology, degradation and release rates. Silk fibroin is widely characterized in the literature for the production of biomaterials, but this work is the first that successfully evaluates the blends silk fibroin/keratin (SF/K) and silk fibroin/elastin (SF/EL) for their application as wound dressings.

  1. Progress in corneal wound healing

    Science.gov (United States)

    Ljubimov, Alexander V.; Saghizadeh, Mehrnoosh

    2015-01-01

    nanocarriers for corneal drug delivery are discussed. Attention is also paid to problems in wound healing understanding and treatment, such as lack of specific epithelial stem cell markers, reliable identification of stem cells, efficient prevention of haze and stromal scar formation, lack of data on wound regulating microRNAs in keratocytes and endothelial cells, as well as virtual lack of targeted systems for drug and gene delivery to select corneal cells. PMID:26197361

  2. Outpatient wound care.

    Science.gov (United States)

    Kravitz, M

    1996-06-01

    As patients are discharged from the acute care setting to the home care setting at a much earlier time in their recovery, surgical wound care will be delivered by patients, family members, and home health care providers rather than by the hospital nurse in a traditional in-patient setting. This trend, which began in the mid-1980s, is expanding to include not just surgical wounds but also surgical complications such as wound dehiscence and traumatic wounds healing by secondary intention. Intensive care nurses are involved in discharge planning from the time the patient is admitted to the ICU. Early planning and teaching regarding wound care, universal precautions, and medical waste disposal have become a vital component of preparing the patient for optimal continuity of care as the transition is made into the community.

  3. Wnt signaling induces epithelial differentiation during cutaneous wound healing

    Directory of Open Access Journals (Sweden)

    Hocking Anne

    2006-01-01

    Full Text Available Abstract Background Cutaneous wound repair in adult mammals does not regenerate the original epithelial architecture and results in altered skin function. We propose that lack of regeneration may be due to the absence of appropriate molecular signals to promote regeneration. In this study, we investigated the regulation of Wnt signaling during cutaneous wound healing and the consequence of activating either the beta-catenin-dependent or beta-catenin-independent Wnt signaling on epidermal architecture during wound repair. Results We determined that the expression of Wnt ligands that typically signal via the beta-catenin-independent pathway is up-regulated in the wound while the beta-catenin-dependent Wnt signaling is activated in the hair follicles adjacent to the wound edge. Ectopic activation of beta-catenin-dependent Wnt signaling with lithium chloride in the wound resulted in epithelial cysts and occasional rudimentary hair follicle structures within the epidermis. In contrast, forced expression of Wnt-5a in the deeper wound induced changes in the interfollicular epithelium mimicking regeneration, including formation of epithelia-lined cysts in the wound dermis, rudimentary hair follicles and sebaceous glands, without formation of tumors. Conclusion These findings suggest that adult interfollicular epithelium is capable of responding to Wnt morphogenic signals necessary for restoring epithelial tissue patterning in the skin during wound repair.

  4. Complements and the Wound Healing Cascade: An Updated Review

    Directory of Open Access Journals (Sweden)

    Hani Sinno

    2013-01-01

    Full Text Available Wound healing is a complex pathway of regulated reactions and cellular infiltrates. The mechanisms at play have been thoroughly studied but there is much still to learn. The health care system in the USA alone spends on average 9 billion dollars annually on treating of wounds. To help reduce patient morbidity and mortality related to abnormal or prolonged skin healing, an updated review and understanding of wound healing is essential. Recent works have helped shape the multistep process in wound healing and introduced various growth factors that can augment this process. The complement cascade has been shown to have a role in inflammation and has only recently been shown to augment wound healing. In this review, we have outlined the biology of wound healing and discussed the use of growth factors and the role of complements in this intricate pathway.

  5. Coordinate regulation of RARgamma2, TBP, and TAFII135 by targeted proteolysis during retinoic acid-induced differentiation of F9 embryonal carcinoma cells

    Directory of Open Access Journals (Sweden)

    Carré Lucie

    2001-03-01

    Full Text Available Abstract Background Treatment of mouse F9 embryonal carcinoma cells with all-trans retinoic acid (T-RA induces differentiation into primitive endodermal type cells. Differentiation requires the action of the receptors for all trans, and 9cis-retinoic acid (RAR and RXR, respectively and is accompanied by growth inhibition, changes in cell morphology, increased apoptosis, proteolytic degradation of the RARγ2 receptor, and induction of target genes. Results We show that the RNA polymerase II transcription factor TFIID subunits TBP and TAFII135 are selectively depleted in extracts from differentiated F9 cells. In contrast, TBP and TAFII135 are readily detected in extracts from differentiated F9 cells treated with proteasome inhibitors showing that their disappearance is due to targeted proteolysis. This regulatory pathway is not limited to F9 cells as it is also seen when C2C12 myoblasts differentiate into myotubes. Targeting of TBP and TAFII135 for proteolysis in F9 cells takes place coordinately with that previously reported for the RARγ2 receptor and is delayed or does not take place in RAR mutant F9 cells where differentiation is known to be impaired or abolished. Moreover, ectopic expression of TAFII135 delays proteolysis of the RARγ2 receptor and impairs primitive endoderm differentiation at an early stage as evidenced by cell morphology, induction of marker genes and apoptotic response. In addition, enhanced TAFII135 expression induces a novel differentiation pathway characterised by the appearance of cells with an atypical elongated morphology which are cAMP resistant. Conclusions These observations indicate that appropriately timed proteolysis of TBP and TAFII135 is required for normal F9 cell differentiation. Hence, in addition to transactivators, targeted proteolysis of basal transcription factors also plays an important role in gene regulation in response to physiological stimuli.

  6. Coordinated maturational regulation of PHEX and renal phosphate transport inhibitory activity: evidence for the pathophysiological role of PHEX in X-linked hypophosphatemia.

    Science.gov (United States)

    Nesbitt, T; Fujiwara, I; Thomas, R; Xiao, Z S; Quarles, L D; Drezner, M K

    1999-12-01

    The mechanism by which inactivating mutations of PHEX (phosphate-regulating gene with homologies to endopeptidases on the X chromosome) cause X-linked hypophosphatemia remains unknown. However, recent reports suggest errant PHEX activity in osteoblasts may fail to inactivate a phosphaturic factor produced by these cells. To test this possibility, we examined coordinated maturational expression of PHEX and production of phosphate transport inhibitory activity in osteoblasts from normal and hyp-mice. We assessed the inhibitory activity in conditioned medium by examining the effects on opossum kidney cell phosphate transport and osteoblast PHEX expression by reverse transcriptase-polymerase chain reaction during a 17-day maturational period. Inhibitory activity increased as a function of osteoblast maturational stage, with no activity after 3 days and persistent activity by 6 days of culture. More significantly, equal phosphate transport inhibitory activity in conditioned medium from normal and hyp-mouse osteoblasts (control 1.90 +/- 0.12, normal 1.48 +/- 0.10, hyp 1.45 +/- 0.04 nmol/mg of protein/minute) was observed at 6 days. However, by 10 days hyp-mouse osteoblasts exhibited greater inhibitory activity than controls, and by 17 days the difference in phosphate transport inhibition maximized (control 2.08 +/- 0.09, normal 1.88 +/- 0.06, hyp 1.58 +/- 0.06 nmol/mg of protein/minute). Concurrently, we observed absent PHEX expression in normal osteoblasts after 3 days, limited production at 6 days, and significant production by day 10 of culture, while hyp-mouse osteoblasts exhibited limited PHEX activity secondary to an inactivating mutation. The data suggest that the presence of inactivating PHEX mutations results in the enhanced renal phosphate transport inhibitory activity exhibited by hyp-mouse osteoblasts.

  7. Enhanced wound contraction in fresh wounds dressed with honey in ...

    African Journals Online (AJOL)

    Background: Due to reports that honey accelerates wound healing, an investigation on its role in wound contraction in fresh wounds inflicted on wistar rats was carried out. Method: Twenty adult male wistar rats had 2cm by 2cm square wound inflicted on their right dorsolateral trunk. They were divided into two groups.

  8. MODERN WOUND DRESSING FOR WOUND INFECTION: AN OVERVIEW

    OpenAIRE

    Novida Rizani

    2012-01-01

    When the tissue of skin is break means a wound is happens. To seal it, many choices of wound healing are available. Moist wound dressing can be better optional than the conservative ones. A bioactive agent that being added at the dressing in fact can increase healing rate of wound, moreover can subjugate wound infection caused by the pathogens, and also capable to prevent it. In this review, there are summary of modern moist wound healing, the wound pathogens, and some of sturdy bioactive age...

  9. A modified collagen gel dressing promotes angiogenesis in a preclinical swine model of chronic ischemic wounds.

    Science.gov (United States)

    Elgharably, Haytham; Ganesh, Kasturi; Dickerson, Jennifer; Khanna, Savita; Abas, Motaz; Ghatak, Piya Das; Dixit, Sriteja; Bergdall, Valerie; Roy, Sashwati; Sen, Chandan K

    2014-01-01

    We recently performed proteomic characterization of a modified collagen gel (MCG) dressing and reported promising effects of the gel in healing full-thickness excisional wounds. In this work, we test the translational relevance of our aforesaid findings by testing the dressing in a swine model of chronic ischemic wounds recently reported by our laboratory. Full-thickness excisional wounds were established in the center of bipedicle ischemic skin flaps on the backs of animals. Ischemia was verified by laser Doppler imaging, and MCG was applied to the test group of wounds. Seven days post wounding, macrophage recruitment to the wound was significantly higher in MCG-treated ischemic wounds. In vitro, MCG up-regulated expression of Mrc-1 (a reparative M2 macrophage marker) and induced the expression of anti-inflammatory cytokine interleukin (IL)-10 and of fibroblast growth factor-basic (β-FGF). An increased expression of CCR2, an M2 macrophage marker, was noted in the macrophages from MCG treated wounds. Furthermore, analyses of wound tissues 7 days post wounding showed up-regulation of transforming growth factor-β, vascular endothelial growth factor, von Willebrand's factor, and collagen type I expression in MCG-treated ischemic wounds. At 21 days post wounding, MCG-treated ischemic wounds displayed higher abundance of proliferating endothelial cells that formed mature vascular structures and increased blood flow to the wound. Fibroblast count was markedly higher in MCG-treated ischemic wound-edge tissue. In addition, MCG-treated wound-edge tissues displayed higher abundance of mature collagen with increased collagen type I : III deposition. Taken together, MCG helped mount a more robust inflammatory response that resolved in a timely manner, followed by an enhanced proliferative phase, angiogenic outcome, and postwound tissue remodeling. Findings of the current study warrant clinical testing of MCG in a setting of ischemic chronic wounds. © 2014 by the Wound

  10. Management of complicated wounds.

    Science.gov (United States)

    Hendrix, Sam M; Baxter, Gary M

    2005-04-01

    Most injuries, including those with significant tissue loss, can be successfully managed with proper therapy. With delayed healing, potential causes for the delay, such as sequestra, foreign bodies, and excessive motion,should be determined and treated to permit complete wound resolution. Horses have the innate ability to heal rapidly; however, minor injuries can quickly turn into complicated wounds, given the severity of the inciting trauma and the less than ideal environment in which the horses are housed. Wound management must focus on a combination of timely surgical and medical intervention to ensure the best potential outcome.

  11. Wording the Wound Man

    Directory of Open Access Journals (Sweden)

    Jack Hartnell

    2017-06-01

    Full Text Available Little is known about the image of the Wound Man, a graphic drawing of a violently wounded figure repeated across a series of European surgical treatises from 1400 onwards. Focusing on the only known English example, preserved in the back of a late fifteenth-century medical miscellany now in the Wellcome Collection, London, this article seeks to unravel the origins and scope of this picture. Considering both the image’s diagrammatic and metaphorical qualities, it presents the Wound Man as a particularly potent site not just of surgical knowledge but of a broader medico-artistic entanglement.

  12. Cuts and puncture wounds

    Science.gov (United States)

    ... 2009:chap 39. Simon BC, Hern HG. Wound management principles. In: Marx JA, Hockberger RS, Walls RM, et al., eds. Rosen's Emergency Medicine: Concepts and Clinical Practice . 8th ed. Philadelphia, PA: Elsevier Saunders; 2014:chap ...

  13. Prevent Bite Wounds

    Science.gov (United States)

    ... Issues Listen Español Text Size Email Print Share Prevent Bite Wounds Page Content Article Body Each year, ... bite Swollen glands that occur above the bite Prevention of Bites and Infections To prevent bites and ...

  14. Ferrets: wound healing and therapy.

    Science.gov (United States)

    Pilny, Anthony A; Hess, Laurie

    2004-01-01

    In all species of mammals, the stages of wound healing are the same, and both host factors and wound characteristics affect how wounds heal. The basic principles of wound care in ferrets, such as lavage, bandaging, and surgical closure, are similar to those in other species; however, knowledge of ferrets' anatomy and pathophysiology, as well as skin conditions commonly seen in ferrets, will help ensure proper wound healing.

  15. TECHNICAL COORDINATION

    CERN Multimedia

    A. Ball

    Overview From a technical perspective, CMS has been in “beam operation” state since 6th November. The detector is fully closed with all components operational and the magnetic field is normally at the nominal 3.8T. The UXC cavern is normally closed with the radiation veto set. Access to UXC is now only possible during downtimes of LHC. Such accesses must be carefully planned, documented and carried out in agreement with CMS Technical Coordination, Experimental Area Management, LHC programme coordination and the CCC. Material flow in and out of UXC is now strictly controlled. Access to USC remains possible at any time, although, for safety reasons, it is necessary to register with the shift crew in the control room before going down.It is obligatory for all material leaving UXC to pass through the underground buffer zone for RP scanning, database entry and appropriate labeling for traceability. Technical coordination (notably Stephane Bally and Christoph Schaefer), the shift crew and run ...

  16. Combat Wound Initiative program.

    Science.gov (United States)

    Stojadinovic, Alexander; Elster, Eric; Potter, Benjamin K; Davis, Thomas A; Tadaki, Doug K; Brown, Trevor S; Ahlers, Stephen; Attinger, Christopher E; Andersen, Romney C; Burris, David; Centeno, Jose; Champion, Hunter; Crumbley, David R; Denobile, John; Duga, Michael; Dunne, James R; Eberhardt, John; Ennis, William J; Forsberg, Jonathan A; Hawksworth, Jason; Helling, Thomas S; Lazarus, Gerald S; Milner, Stephen M; Mullick, Florabel G; Owner, Christopher R; Pasquina, Paul F; Patel, Chirag R; Peoples, George E; Nissan, Aviram; Ring, Michael; Sandberg, Glenn D; Schaden, Wolfgang; Schultz, Gregory S; Scofield, Tom; Shawen, Scott B; Sheppard, Forest R; Stannard, James P; Weina, Peter J; Zenilman, Jonathan M

    2010-07-01

    The Combat Wound Initiative (CWI) program is a collaborative, multidisciplinary, and interservice public-private partnership that provides personalized, state-of-the-art, and complex wound care via targeted clinical and translational research. The CWI uses a bench-to-bedside approach to translational research, including the rapid development of a human extracorporeal shock wave therapy (ESWT) study in complex wounds after establishing the potential efficacy, biologic mechanisms, and safety of this treatment modality in a murine model. Additional clinical trials include the prospective use of clinical data, serum and wound biomarkers, and wound gene expression profiles to predict wound healing/failure and additional clinical patient outcomes following combat-related trauma. These clinical research data are analyzed using machine-based learning algorithms to develop predictive treatment models to guide clinical decision-making. Future CWI directions include additional clinical trials and study centers and the refinement and deployment of our genetically driven, personalized medicine initiative to provide patient-specific care across multiple medical disciplines, with an emphasis on combat casualty care.

  17. Acute and Impaired Wound Healing: Pathophysiology and Current Methods for Drug Delivery, Part 1: Normal and Chronic Wounds: Biology, Causes, and Approaches to Care

    Science.gov (United States)

    Demidova-Rice, Tatiana N.; Hamblin, Michael R.; Herman, Ira M.

    2012-01-01

    This is the first installment of 2 articles that discuss the biology and pathophysiology of wound healing, review the role that growth factors play in this process, and describe current ways of growth factor delivery into the wound bed. Part 1 discusses the latest advances in clinicians’ understanding of the control points that regulate wound healing. Importantly, biological similarities and differences between acute and chronic wounds are considered, including the signaling pathways that initiate cellular and tissue responses after injury, which may be impeded during chronic wound healing. PMID:22713781

  18. Crawling cells can close wounds without purse strings or signaling.

    Directory of Open Access Journals (Sweden)

    Pilhwa Lee

    2011-03-01

    Full Text Available When a gash or gouge is made in a confluent layer of epithelial cells, the cells move to fill in the "wound." In some cases, such as in wounded embryonic chick wing buds, the movement of the cells is driven by cortical actin contraction (i.e., a purse string mechanism. In adult tissue, though, cells apparently crawl to close wounds. At the single cell level, this crawling is driven by the dynamics of the cell's actin cytoskeleton, which is regulated by a complex biochemical network, and cell signaling has been proposed to play a significant role in directing cells to move into the denuded area. However, wounds made in monolayers of Madin-Darby canine kidney (MDCK cells still close even when a row of cells is deactivated at the periphery of the wound, and recent experiments show complex, highly-correlated cellular motions that extend tens of cell lengths away from the boundary. These experiments suggest a dominant role for mechanics in wound healing. Here we present a biophysical description of the collective migration of epithelial cells during wound healing based on the basic motility of single cells and cell-cell interactions. This model quantitatively captures the dynamics of wound closure and reproduces the complex cellular flows that are observed. These results suggest that wound healing is predominantly a mechanical process that is modified, but not produced, by cell-cell signaling.

  19. Wound healing potential of adipose tissue stem cell extract.

    Science.gov (United States)

    Na, You Kyung; Ban, Jae-Jun; Lee, Mijung; Im, Wooseok; Kim, Manho

    2017-03-25

    Adipose tissue stem cells (ATSCs) are considered as a promising source in the field of cell therapy and regenerative medicine. In addition to direct cell replacement using stem cells, intercellular molecule exchange by stem cell secretory factors showed beneficial effects by reducing tissue damage and augmentation of endogenous repair. Delayed cutaneous wound healing is implicated in many conditions such as diabetes, aging, stress and alcohol consumption. However, the effects of cell-free extract of ATSCs (ATSC-Ex) containing secretome on wound healing process have not been investigated. In this study, ATSC-Ex was topically applied on the cutaneous wound and healing speed was examined. As a result, wound closure was much faster in the cell-free extract treated wound than control wound at 4, 6, 8 days after application of ATSC-Ex. Dermal fibroblast proliferation, migration and extracellular matrix (ECM) production are critical aspects of wound healing, and the effects of ATSC-Ex on human dermal fibroblast (HDF) was examined. ATSC-Ex augmented HDF proliferation in a dose-dependent manner and migration ability was enhanced by extract treatment. Representative ECM proteins, collagen type I and matrix metalloproteinase-1, are significantly up-regulated by treatment of ATSC-Ex. Our results suggest that the ATSC-Ex have improving effect of wound healing and can be the potential therapeutic candidate for cutaneous wound healing. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Chemokine Involvement in Fetal and Adult Wound Healing

    Science.gov (United States)

    Balaji, Swathi; Watson, Carey L.; Ranjan, Rajeev; King, Alice; Bollyky, Paul L.; Keswani, Sundeep G.

    2015-01-01

    Significance: Fetal wounds heal with a regenerative phenotype that is indistinguishable from surrounding skin with restored skin integrity. Compared to this benchmark, all postnatal wound healing is impaired and characterized by scar formation. The biologic basis of the fetal regenerative phenotype can serve as a roadmap to recapitulating regenerative repair in adult wounds. Reduced leukocyte infiltration, likely mediated, in part, through changes in the chemokine milieu, is a fundamental feature of fetal wound healing. Recent Advances: The contributions of chemokines to wound healing are a topic of active investigation. Recent discoveries have opened the possibility of targeting chemokines therapeutically to treat disease processes and improve healing capability, including the possibility of achieving a scarless phenotype in postnatal wounds. Critical Issues: Successful wound healing is a complex process, in which there is a significant interplay between multiple cell types, signaling molecules, growth factors, and extracellular matrix. Chemokines play a crucial role in this interplay and have been shown to have different effects in various stages of the healing process. Understanding how these chemokines are locally produced and regulated during wound healing and how the chemokine milieu differs in fetal versus postnatal wounds may help us identify ways in which we can target chemokine pathways. Future Directions: Further studies on the role of chemokines and their role in the healing process will greatly advance the potential for using these molecules as therapeutic targets. PMID:26543680

  1. Managing painful chronic wounds: the Wound Pain Management Model

    DEFF Research Database (Denmark)

    Price, Patricia; Fogh, Karsten; Glynn, Chris

    2007-01-01

    Chronic wound pain is not well understood and the literature is limited. Six of 10 patients venous leg ulcer experience pain with their ulcer, and similar trends are observed for other chronic wounds. Chronic wound pain can lead to depression and the feeling of constant tiredness. Pain related...... to the wound should be handled as one of the main priorities in chronic wound management together with addressing the cause. Management of pain in chronic wounds depends on proper assessment, reporting and documenting patient experiences of pain. Assessment should be based on six critical dimensions...... document persistent wound pain and not to develop a treatment and monitoring strategy to improve the lives of persons with chronic wounds. Unless wound pain is optimally managed, patient suffering and costs to health care systems will increase. Udgivelsesdato: 2007-Apr...

  2. Coordinated Regulation of Anthocyanin Biosynthesis Genes Confers Varied Phenotypic and Spatial-Temporal Anthocyanin Accumulation in Radish (Raphanus sativusL.).

    Science.gov (United States)

    Muleke, Everlyne M'mbone; Fan, Lianxue; Wang, Yan; Xu, Liang; Zhu, Xianwen; Zhang, Wei; Cao, Yang; Karanja, Benard K; Liu, Liwang

    2017-01-01

    Anthocyanins are natural pigments that have important functions in plant growth and development. Radish taproots are rich in anthocyanins which confer different taproot colors and are potentially beneficial to human health. The crop differentially accumulates anthocyanin during various stages of growth, yet molecular mechanisms underlying this differential anthocyanin accumulation remains unknown. In the present study, transcriptome analysis was used to concisely identify putative genes involved in anthocyanin biosynthesis in radish. Spatial-temporal transcript expressions were then profiled in four color variant radish cultivars. From the total transcript sequences obtained through illumina sequencing, 102 assembled unigenes, and 20 candidate genes were identified to be involved in anthocyanin biosynthesis. Fifteen genomic sequences were isolated and sequenced from radish taproot. The length of these sequences was between 900 and 1,579 bp, and the unigene coverage to all of the corresponding cloned sequences was more than 93%. Gene structure analysis revealed that RsF3 ' H is intronless and anthocyanin biosynthesis genes (ABGs) bear asymmetrical exons, except RsSAM . Anthocyanin accumulation showed a gradual increase in the leaf of the red radish and the taproot of colored cultivars during development, with a rapid increase at 30 days after sowing (DAS), and the highest content at maturity. Spatial-temporal transcriptional analysis of 14 genes revealed detectable expressions of 12 ABGs in various tissues at different growth levels. The investigation of anthocyanin accumulation and gene expression in four color variant radish cultivars, at different stages of development, indicated that total anthocyanin correlated with transcript levels of ABGs, particularly RsUFGT, RsF3H, RsANS, RsCHS3 and RsF3 ' H1 . Our results suggest that these candidate genes play key roles in phenotypic and spatial-temporal anthocyanin accumulation in radish through coordinated regulation

  3. Nurse-managed wound clinic. A case study in success.

    Science.gov (United States)

    Crumbley, D R; Ice, R C; Cassidy, R

    1999-01-01

    The wound Care Clinic at Naval Hospital Charleston is a nurse-managed ambulatory clinic that has demonstrated the successful application of nursing case management in caring for patients with chronic and complex wounds. Nursing case management is an outcomes-based system of assessment, planning, provision of nursing services, coordination of interdisciplinary efforts, education, and referral. Nursing case management has been shown, in the literature and at Naval Hospital Charleston, to be an extension of role of professional nursing practice and results in decreased costs, improved quality of care, faster wound healing times, decreased complications, and greater coordination of care between specialty disciplines. These positive results are illustrated in several case studies. Nursing case management has many implications for the successful implementation of any healthcare delivery system where decreased costs and improved quality of care are valued, and it has special benefit in the complex management of chronically ill patients.

  4. Combination of negative pressure wound therapy and acoustic pressure wound therapy for treatment of infected surgical wounds: a case series.

    Science.gov (United States)

    Liguori, Paul A; Peters, Kim L; Bowers, Jolene M

    2008-05-01

    The optimal wound therapy for healing infected wounds post surgery or surgical debridement has not been established. Negative pressure wound therapy and acoustic pressure wound therapy are advanced wound-healing modalities that apply forms of mechanical pressure to wound tissue in an effort to promote healing by stimulating cellular proliferation. Using a combination of negative pressure wound therapy and acoustic pressure wound therapy was evaluated in a series of six patients with large, infected surgical wounds presenting with moderate to large amounts of serosanguineous drainage. After concurrent treatment with both modalities (range: 4 to 12 weeks), wound volume was reduced by 99% to 100% in all wounds except one wound for which depth at end of treatment was not measurable due to hypergranulation. Similarly, wound surface area was reduced by 82% to 100%, with the exception of the hypergranular wound, which decreased in size by 60%. Serosanguineous wound drainage was reduced in four wounds and remained unchanged in two wounds.

  5. Wound pH depends on actual wound size

    CERN Document Server

    Sirkka, T; Apell, S P

    2016-01-01

    Wound healing is an intricate process that involves many types of cells, reaction pathways as well as chemical, physical and electrical cues. Since biochemical reactions and physiological events are pH-dependent we study here pH as an important major characteristic of the wound healing process in the presence of endogenous and exogenous electric fields. Our model gives the spatial pH distribution in a wound. In particular we isolate a number of dimensionless quantities which sets the length, energy and time scales governing the wound healing process and which can be experimentally tested. Most interesting finding is that wound pH depends on actual wound size.

  6. TECHNICAL COORDINATION

    CERN Multimedia

    A. Ball

    2010-01-01

    Operational Experience At the end of the first full-year running period of LHC, CMS is established as a reliable, robust and mature experiment. In particular common systems and infrastructure faults accounted for <0.6 % CMS downtime during LHC pp physics. Technical operation throughout the entire year was rather smooth, the main faults requiring UXC access being sub-detector power systems and rack-cooling turbines. All such problems were corrected during scheduled technical stops, in the shadow of tunnel access needed by the LHC, or in negotiated accesses or access extensions. Nevertheless, the number of necessary accesses to the UXC averaged more than one per week and the technical stops were inevitably packed with work packages, typically 30 being executed within a few days, placing a high load on the coordination and area management teams. It is an appropriate moment for CMS Technical Coordination to thank all those in many CERN departments and in the Collaboration, who were involved in CMS techni...

  7. The molecular biology in wound healing & non-healing wound.

    Science.gov (United States)

    Qing, Chun

    2017-08-01

    The development of molecular biology and other new biotechnologies helps us to recognize the wound healing and non-healing wound of skin in the past 30 years. This review mainly focuses on the molecular biology of many cytokines (including growth factors) and other molecular factors such as extracellular matrix (ECM) on wound healing. The molecular biology in cell movement such as epidermal cells in wound healing was also discussed. Moreover many common chronic wounds such as pressure ulcers, leg ulcers, diabetic foot wounds, venous stasis ulcers, etc. usually deteriorate into non-healing wounds. Therefore the molecular biology such as advanced glycation end products (AGEs) and other molecular factors in diabetes non-healing wounds were also reviewed. Copyright © 2017 Daping Hospital and the Research Institute of Surgery of the Third Military Medical University. Production and hosting by Elsevier B.V. All rights reserved.

  8. Planned development and coordination of public policies as a starting point in the harmonization of national regulations with the EU aquis

    Directory of Open Access Journals (Sweden)

    Jovanić Tatjana

    2014-01-01

    Full Text Available One of the most important aspects of harmonizing Serbian legislation with the EU law, however still neglected in Serbia, is the mutual relationship between the design and coordination of public policies on the one hand, and the harmonization of legislation in the course of negotiations for EU accession, on the other hand. This aspect has been largely neglected because of the misuse of emergency procedure for adopting legislation in order to assure compatibility with the EU law, but also due to underdeveloped regulatory policies, which has been reduced to the guillotine of legislation, instead of developing a cycle of policy and analytical phase that precedes the drafting of legislation. Although the negotiating structure of European integration has been improved, the Negotiation Team and Coordination Body certainly can not replace the role of policy makers in their creation. Since the new Law on Ministries envisaged the creation of the Secretariat for the coordination of public policies, an institutional prerequisite for the implementation of the function of harmonizing public policy proposals has been put forward, but is not yet clear what powers in the policy cycle this institution would have. In any case, this administrative body will certainly complement Serbian coordination structure in the negotiation process.

  9. Wound healing and treating wounds: Differential diagnosis and evaluation of chronic wounds.

    Science.gov (United States)

    Morton, Laurel M; Phillips, Tania J

    2016-04-01

    Wounds are an excellent example of how the field of dermatology represents a cross-section of many medical disciplines. For instance, wounds may be caused by trauma, vascular insufficiency, and underlying medical conditions, such as diabetes, hypertension, and rheumatologic and inflammatory disease. This continuing medical education article provides an overview of wound healing and the pathophysiology of chronic wounds and reviews the broad differential diagnosis of chronic wounds. It also describes the initial steps necessary in evaluating a chronic wound and determining its underlying etiology. Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  10. Burn wound: How it differs from other wounds?

    Directory of Open Access Journals (Sweden)

    V K Tiwari

    2012-01-01

    Full Text Available Management of burn injury has always been the domain of burn specialists. Since ancient time, local and systemic remedies have been advised for burn wound dressing and burn scar prevention. Management of burn wound inflicted by the different physical and chemical agents require different regimes which are poles apart from the regimes used for any of the other traumatic wounds. In extensive burn, because of increased capillary permeability, there is extensive loss of plasma leading to shock while whole blood loss is the cause of shock in other acute wounds. Even though the burn wounds are sterile in the beginning in comparison to most of other wounds, yet, the death in extensive burns is mainly because of wound infection and septicemia, because of the immunocompromised status of the burn patients. Eschar and blister are specific for burn wounds requiring a specific treatment protocol. Antimicrobial creams and other dressing agents used for traumatic wounds are ineffective in deep burns with eschar. The subeschar plane harbours the micro-organisms and many of these agents are not able to penetrate the eschar. Even after complete epithelisation of burn wound, remodelling phase is prolonged. It may take years for scar maturation in burns. This article emphasizes on how the pathophysiology, healing and management of a burn wound is different from that of other wounds.

  11. The wound/burn guidelines - 1: Wounds in general.

    Science.gov (United States)

    Inoue, Yuji; Hasegawa, Minoru; Maekawa, Takeo; Le Pavoux, Andres; Asano, Yoshihide; Abe, Masatoshi; Ishii, Takayuki; Ito, Takaaki; Isei, Taiki; Imafuku, Shinichi; Irisawa, Ryokichi; Ohtsuka, Masaki; Ohtsuka, Mikio; Ogawa, Fumihide; Kadono, Takafumi; Kodera, Masanari; Kawakami, Tamihiro; Kawaguchi, Masakazu; Kukino, Ryuichi; Kono, Takeshi; Sakai, Keisuke; Takahara, Masakazu; Tanioka, Miki; Nakanishi, Takeshi; Nakamura, Yasuhiro; Hashimoto, Akira; Hayashi, Masahiro; Fujimoto, Manabu; Fujiwara, Hiroshi; Matsuo, Koma; Madokoro, Naoki; Yamasaki, Osamu; Yoshino, Yuichiro; Tachibana, Takao; Ihn, Hironobu

    2016-04-01

    The Japanese Dermatological Association determined to prepare the Wound/Burn Guidelines focusing on treatments, catering to needs for the clinical practice of dermatology. Among these guidelines, "Wounds in General" was intended to explain knowledge necessary "to heal wounds" without specifying particular disorders. © 2016 Japanese Dermatological Association.

  12. NEGATIVE PRESSURE WOUND THERAPY (NPWT) FOR THE ...

    African Journals Online (AJOL)

    NEGATIVE PRESSURE WOUND THERAPY (NPWT) FOR THE MANAGEMENT OF LAPAROSTOMY WOUNDS: ... Negative pressure wound therapy (NPWT) is one of the new additions to the armamentarium of laparostomy wound management to achieve the above (8). ... However, second day post operatively she.

  13. Differential Apoptosis in Mucosal and Dermal Wound Healing.

    Science.gov (United States)

    Johnson, Ariel; Francis, Marybeth; DiPietro, Luisa Ann

    2014-12-01

    Objectives: Dermal and mucosal healing are mechanistically similar. However, scarring and closure rates are dramatically improved in mucosal healing, possibly due to differences in apoptosis. Apoptosis, nature's preprogrammed form of cell death, occurs via two major pathways, extrinsic and intrinsic, which intersect at caspase3 (Casp3) cleavage and activation. The purpose of this experiment was to identify the predominant pathways of apoptosis in mucosal and dermal wound healing. Approach: Wounds (1 mm biopsy punch) were made in the dorsal skin (n=3) or tongue (n=3) of female Balb/C mice aged 6 weeks. Wounds were harvested at 6 h, 24 h, day 3 (D3), D5, D7, and D10. RNA was isolated and analyzed using real time reverse transcriptase-polymerase chain reaction. Expression levels for genes in the intrinsic and extrinsic apoptotic pathways were compared in dermal and mucosal wounds. Results: Compared to mucosal healing, dermal wounds exhibited significantly higher expression of Casp3 (at D5; pInnovation: Our observations indicate differential execution of apoptosis in oral wound healing compared to skin. Conclusion: Expression patterns of key regulators of apoptosis in wound healing indicate that apoptosis occurs predominantly through the intrinsic pathway in the healing mucosa, but predominantly through the extrinsic pathway in the healing skin. The identification of differences in the apoptotic pathways in skin and mucosal wounds may allow the development of therapeutics to improve skin healing.

  14. Matrix metalloproteinases: The sculptors of chronic cutaneous wounds.

    Science.gov (United States)

    Krishnaswamy, Venkat Raghavan; Mintz, Dvir; Sagi, Irit

    2017-11-01

    Cutaneous wound healing is a complex mechanism with multiple processes orchestrating harmoniously for structural and functional restoration of the damaged tissue. Chronic non-healing wounds plagued with infection create a major healthcare burden and is one of the most frustrating clinical problems. Chronic wounds are manifested by prolonged inflammation, defective re-epithelialization and haphazard remodeling. Matrix metalloproteinases (MMPs) are zinc dependent enzymes that play cardinal functions in wound healing. Understanding the pathological events mediated by MMPs during wound healing may pave way in identifying novel drug targets for chronic wounds. Here, we discuss the functions and skewed regulation of different MMPs during infection and chronic tissue repair. This review also points out the potential of MMPs and their inhibitors as therapeutic agents in treating chronic wounds during distinct phases of the wound healing. This article is part of a Special Issue entitled: Proteolysis as a Regulatory Event in Pathophysiology edited by Stefan Rose-John. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Wound morbidity after kidney transplant

    NARCIS (Netherlands)

    Fockens, M. Matthijs; Alberts, Victor P.; Bemelman, Frederike J.; van der Pant, Karlijn A. M. I.; Idu, Mirza M.

    2015-01-01

    Wound morbidity is an important surgical complication after kidney transplant. To assess risk factors for postoperative wound complications and the impact of such complications on outcomes of kidney transplant. Retrospectively, 108 consecutive kidney transplant patients between January 2010 and

  16. GhWRKY40, a multiple stress-responsive cotton WRKY gene, plays an important role in the wounding response and enhances susceptibility to ralstonia solanacearum infection in transgenic Nicotiana benthamiana.

    Directory of Open Access Journals (Sweden)

    Xiuling Wang

    Full Text Available WRKY transcription factors form one of the largest transcription factor families and function as important components in the complex signaling processes that occur during plant stress responses. However, relative to the research progress in model plants, far less information is available on the function of WRKY proteins in cotton. In the present study, we identified the GhWRKY40 gene in cotton (Gossypium hirsutum and determined that the GhWRKY40 protein is targeted to the nucleus and is a stress-inducible transcription factor. The GhWRKY40 transcript level was increased upon wounding and infection with the bacterial pathogen Ralstonia solanacearum. The overexpression of GhWRKY40 down-regulated most of the defense-related genes, enhanced the wounding tolerance and increased the susceptibility to R. solanacearum. Consistent with a role in multiple stress responses, we found that the GhWRKY40 transcript level was increased by the stress hormones salicylic acid (SA, methyl jasmonate (MeJA and ethylene (ET. Moreover, GhWRKY40 interacted with the MAPK kinase GhMPK20, as shown using yeast two-hybrid and bimolecular fluorescence complementation systems. Collectively, these results suggest that GhWRKY40 is regulated by SA, MeJA and ET signaling and coordinates responses to wounding and R. solanacearum attack. These findings highlight the importance of WRKYs in regulating wounding- and pathogen-induced responses.

  17. Initial Management of Traumatic Wounds.

    Science.gov (United States)

    Devriendt, Nausikaa; de Rooster, Hilde

    2017-11-01

    When traumatic wounds are quickly and accurately treated, morbidity and costs can be significantly decreased. Several factors, such as time delay between injury and treatment, the degree of contamination, extension and depth of the wound, and the mechanism of injury, influence the treatment and prognosis and stress the importance of a patient-specific approach. Although all traumatic wounds are contaminated, antibiotic therapy is seldom required if correct wound management is installed. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Wound Drainage Culture (For Parents)

    Science.gov (United States)

    ... a Voice in Health Care Decisions Wound Drainage Culture KidsHealth > For Parents > Wound Drainage Culture Print A A A What's in this article? ... Have Questions What It Is A wound drainage culture is a test to detect germs such as ...

  19. Trends in Surgical Wound Healing

    DEFF Research Database (Denmark)

    Gottrup, F.

    2008-01-01

    The understanding of acute and chronic wound pathophysiology has progressed considerably over the past decades. Unfortunately, improvement in clinical practice has not followed suit, although new trends and developments have improved the outcome of wound treatment in many ways. This review focuses...... on promising clinical development in major wound problems in general and on postoperative infections in particular Udgivelsesdato: 2008...

  20. Gunshot wounds -- aftercare

    Science.gov (United States)

    ... clean towel. Let the wound air dry. After Effects Being shot by a gun is traumatic. You may feel shock, fear for your safety, depression, or anger as a result. These are completely normal feelings for someone who has been through a traumatic event . These feelings are not signs of weakness. You ...

  1. Healing Invisible Wounds

    Science.gov (United States)

    Adams, Erica J.

    2010-01-01

    As many as 9 in 10 justice-involved youth are affected by traumatic childhood experiences. According to "Healing Invisible Wounds: Why Investing in Trauma-Informed Care for Children Makes Sense," between 75 and 93 percent of youth currently incarcerated in the justice system have had at least one traumatic experience, including sexual…

  2. Wound Infections PSA (:30)

    Centers for Disease Control (CDC) Podcasts

    2017-10-25

    This 30 second public service announcement is about how to avoid a wound infection after a disaster.  Created: 10/25/2017 by Centers for Disease Control and Prevention (CDC).   Date Released: 10/25/2017.

  3. Fungal Wound Infection

    Centers for Disease Control (CDC) Podcasts

    2016-01-28

    Dr. David Tribble, acting director of the infectious disease clinical research program at Uniformed Services University of the Health Sciences, discusses fungal wound infections after combat trauma.  Created: 1/28/2016 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 1/28/2016.

  4. RUN COORDINATION

    CERN Multimedia

    C. Delaere

    2013-01-01

    Since the LHC ceased operations in February, a lot has been going on at Point 5, and Run Coordination continues to monitor closely the advance of maintenance and upgrade activities. In the last months, the Pixel detector was extracted and is now stored in the pixel lab in SX5; the beam pipe has been removed and ME1/1 removal has started. We regained access to the vactank and some work on the RBX of HB has started. Since mid-June, electricity and cooling are back in S1 and S2, allowing us to turn equipment back on, at least during the day. 24/7 shifts are not foreseen in the next weeks, and safety tours are mandatory to keep equipment on overnight, but re-commissioning activities are slowly being resumed. Given the (slight) delays accumulated in LS1, it was decided to merge the two global runs initially foreseen into a single exercise during the week of 4 November 2013. The aim of the global run is to check that we can run (parts of) CMS after several months switched off, with the new VME PCs installed, th...

  5. RUN COORDINATION

    CERN Multimedia

    Christophe Delaere

    2013-01-01

    The focus of Run Coordination during LS1 is to monitor closely the advance of maintenance and upgrade activities, to smooth interactions between subsystems and to ensure that all are ready in time to resume operations in 2015 with a fully calibrated and understood detector. After electricity and cooling were restored to all equipment, at about the time of the last CMS week, recommissioning activities were resumed for all subsystems. On 7 October, DCS shifts began 24/7 to allow subsystems to remain on to facilitate operations. That culminated with the Global Run in November (GriN), which   took place as scheduled during the week of 4 November. The GriN has been the first centrally managed operation since the beginning of LS1, and involved all subdetectors but the Pixel Tracker presently in a lab upstairs. All nights were therefore dedicated to long stable runs with as many subdetectors as possible. Among the many achievements in that week, three items may be highlighted. First, the Strip...

  6. Complex wounds Feridas complexas

    Directory of Open Access Journals (Sweden)

    Marcus Castro Ferreira

    2006-01-01

    Full Text Available Complex wound is the term used more recently to group those well-known difficult wounds, either chronic or acute, that challenge medical and nursing teams. They defy cure using conventional and simple "dressings" therapy and currently have a major socioeconomic impact. The purpose of this review is to bring these wounds to the attention of the health-care community, suggesting that they should be treated by multidisciplinary teams in specialized hospital centers. In most cases, surgical treatment is unavoidable, because the extent of skin and subcutaneous tissue loss requires reconstruction with grafts and flaps. New technologies, such as the negative pressure device, should be introduced. A brief review is provided of the major groups of complex wounds-diabetic wounds, pressure sores, chronic venous ulcers, post-infection soft-tissue gangrenes, and ulcers resulting from vasculitis.Ferida complexa é uma nova definição para identificar aquelas feridas crônicas e algumas agudas já bem conhecidas e que desafiam equipes médicas e de enfermagem. São difíceis de serem resolvidas usando tratamentos convencionais e simples curativos. Têm atualmente grande impacto sócio-econômico. Esta revisão procura atrair atenção da comunidade de profissionais de saúde para estas feridas, sugerindo que devam ser tratadas por equipe multidisciplinar em centro hospitalar especializado. Na maioria dos casos o tratamento cirúrgico deve ser indicado, uma vez que a perda de pele e tecido subcutâneo é extensa, necessitando de reconstrução com enxertos e retalhos. Nova tecnologia, como uso da terapia por pressão negativa foi introduzido. Breves comentários sobre os principais grupos de feridas complexas: pé diabético, úlceras por pressão, úlceras venosas, síndrome de Fournier e vasculites.

  7. Intestinal trefoil factor/TFF3 promotes re-epithelialization of corneal wounds.

    Science.gov (United States)

    Paulsen, Friedrich P; Woon, Chee-Wai; Varoga, Deike; Jansen, Anne; Garreis, Fabian; Jäger, Kristin; Amm, Marita; Podolsky, Daniel K; Steven, Philipp; Barker, Nicholas P; Sel, Saadettin

    2008-05-09

    Disorders of wound healing characterized by impaired or delayed re-epithelialization are a serious medical problem. These conditions affect many tissues, are painful, and are difficult to treat. In this study using cornea as a model, we demonstrate the importance of trefoil factor 3 (TFF3, also known as intestinal trefoil factor) in re-epithelialization of wounds. In two different models of corneal wound healing, alkali- and laser-induced corneal wounding, we analyzed the wound healing process in in vivo as well as in combined in vivo/in vitro model in wild type (Tff3(+)(/)(+)) and Tff3-deficient (Tff3(-)(/)(-)) mice. Furthermore, we topically applied different concentrations of recombinant human TFF3 (rTFF3) peptide on the wounded cornea to determine the efficacy of rTFF3 on corneal wound healing. We found that Tff3 peptide is not expressed in intact corneal epithelium, but its expression is extensively up-regulated after epithelial injury. Re-epithelialization of corneal wounds in Tff3(-/-) mice is significantly prolonged in comparison to Tff3(+/+) mice. In addition, exogenous application of rTFF3 to the alkali-induced corneal wounds accelerates significantly in in vivo and in combined in vivo/in vitro model wound healing in Tff3(+/+) and Tff3(-/-) mice. These findings reveal a pivotal role for Tff3 in corneal wound healing mechanism and have broad implications for developing novel therapeutic strategies for treating nonhealing wounds.

  8. Incisional Negative Pressure Wound Therapy

    DEFF Research Database (Denmark)

    Hyldig, Nana; Birke-Sorensen, Hanne; Kruse, Marie

    Aim: Postoperative wound complications make many surgical procedures unnecessarily complex, particularly in high-risk patients. Negative Pressure Wound Therapy is well recognized in the management of open wounds. In recent years, it has been introduced as well in the management of closed surgical...... incisions to reduce postoperative wound complications, though the evidence base to support this intervention is limited. The aim of this study was to assess if Negative Pressure Wound Therapy (NPWT) reduces postoperative complications when applied on closed surgical incisions. Method: A systematic review...

  9. Smad2 decelerates re-epithelialization during gingival wound healing.

    Science.gov (United States)

    Tomikawa, K; Yamamoto, T; Shiomi, N; Shimoe, M; Hongo, S; Yamashiro, K; Yamaguchi, T; Maeda, H; Takashiba, S

    2012-08-01

    During periodontal regeneration, inhibition of gingival downgrowth is necessary to promote migration of mesenchymal cells into the defects. Transforming growth factor (TGF)-β is a pleiotropic cytokine that has numerous cell functions, including regulation of epithelial growth. Recent studies have shown that Smad2, a downstream transcription factor of TGF-β, plays crucial roles in wound healing in the epithelia. Therefore, we investigated the effects of Smad2 overexpression on re-epithelialization of gingival wounds. Transgenic mice overexpressing smad2 driven by the keratin 14 promoter (k14-smad2) were confirmed to have significant Smad2 phosphorylation in gingival basal epithelia. Punch wounds were made in the palatal gingiva, and wound healing was assessed histologically for 7 days. Re-epithelialization was significantly retarded on day 2, while collagen deposition was enhanced on day 7 in k14-smad2 compared with wild-type mice. Moreover, expression of keratin 16 (K16), an indicator of keratinocyte migration, was significantly inhibited in wound-edge keratinocytes in k14-smad2. The inhibition of K16 coincided with the induction of Smad2 in the corresponding epithelia, while BrdU incorporation was unaffected. These results indicated that Smad2 has inhibitory effects in regulating keratinocyte migration during gingival wound healing. TGF-β/Smad2 signaling mediating alteration of K16 expression must be tightly regulated during periodontal regeneration.

  10. Ballistics reviews: mechanisms of bullet wound trauma.

    Science.gov (United States)

    Maiden, Nicholas

    2009-01-01

    The location of an entrance wound (bullet placement) and the projectile path are the most important factors in causing significant injury or death following a shooting. The head followed by the torso are the most vulnerable areas, with incapacitation resulting from central nervous system (brain or cord) disruption, or massive organ destruction with hemorrhage. Tissue and organ trauma result from the permanent wound cavity caused by direct destruction by the bullet, and also from radial stretching of surrounding tissues causing a temporary wound cavity. The extent of tissue damage is influenced by the type of bullet, its velocity and mass, as well as the physical characteristics of the tissues. The latter includes resistance to strain, physical dimensions of an organ, and the presence or absence of surrounding anatomical constraints. Bullet shape and construction will also affect tissue damage and bullets which display greater yaw will be associated with increased temporary cavitation. Military bullet designs do not include bullets that will expand or flatten as these cause greater wound trauma and are regulated by convention.

  11. Melting graft wound syndrome

    Directory of Open Access Journals (Sweden)

    Shiou-Mei Chen

    2017-09-01

    Full Text Available Melting graft wound syndrome is characterized by progressive epidermal loss from a previously well-taken skin graft, healed burn, or donor site. It may result in considerable morbidity and require prolonged treatment. We report a 23-year-old flame-burned patient with second- to third-degree burns involving more than 70% of the total body surface area, whose condition was complicated with septic shock. The patient presented with erosions and ulcers occurring on previously well-taken skin graft recipient sites over both legs and progressive epidermal loss on donor sites over the back. The patient's presentation was compatible with the diagnosis of melting graft wound syndrome, and we successfully treated the patient with debridement and supportive treatment.

  12. Burn Wound Infection

    Science.gov (United States)

    1981-09-01

    generalized. Clinically, the like- controlled Pseudomonas burn wound infection in most lihood of septicemia appears to increase as the area of patients (2,4...31 patients, dida, Coccidiodes, Phycomyces, and Rhizopus . In 69 of pneumonia was the primary septic process in 27 (20 of these 75 patients (92%), the...carried out as described above and appropriate systemic anti- to which the invading organisms were sensitive and fungal agents are employed to control

  13. Fungal Burn Wound Infection

    Science.gov (United States)

    1991-01-01

    Aspergillus), Blasto- T he use of effective topical chemotherapeutic agents to myces (Candida), and Zygomycetes (Mucor, Rhizopus ).6 reduce...below the infected burn wound . If the infection was controlled by these measures and the patient’s condition permit- ted, the involved area was...species, 18%; Mucor species and Rhizopus species, acetate in the morning and silver sulfadiazine in the evening. Prophy- 9.1%; and Microspora species and

  14. Telemedicine in wound care.

    Science.gov (United States)

    Chanussot-Deprez, Caroline; Contreras-Ruiz, José

    2008-12-01

    Telemedical wound care is one of the applications of teledermatology. We present our experience using telemedicine in the successful assessment and treatment of three patients with hard-to-heal ulcers. Three patients were seen at the PEMEX General Hospital in Veracruz, Mexico. The first patient was a 53-year-old man with hypertension, morbid obesity, chronic venous insufficiency, recurrent erysipelas, leg ulcers and lymphoedema. There was one ulcer on his left lower leg (20 x 10 cm) and one on his right leg (9 x 7 cm). The second patient was a 73-year-old woman with class III obesity and ulcers in her right leg, secondary to surgical debridement of bullous erysipelas. The third patient was a 51-year-old female with rheumatoid arthritis with one ulcer on each leg and chronic lymphostasis. Photographs with a digital camera were taken and sent weekly via email to a wound care specialist in Mexico City. The photographs allowed the expert to diagnose and evaluate the chronic wounds periodically. In the present cases, telemedicine allowed us to have a rapid evaluation, diagnosis and treatment. The images were of enough quality to be useful and small enough to be sent via regular email to the remote physician who immediately gave his feedback. The expert was confident to give therapeutic recommendations in this way, and we considered this method to be very cost-effective, saving the patient and the health care system, especially in transportation.

  15. Carcinogenesis and diabetic wound healing: evidences of parallelism.

    Science.gov (United States)

    Singh, Kanhaiya; Singh, Kiran

    2015-01-01

    There is a close association of chronic tissue damage, inflammation and cancer. A chronic injury may contribute to sustained healing response leading to fibrosis, organ failure and carcinogenesis. Wounds created due to mechanical or patho-physiological insults, generally follow a sophisticated series of mutually coherent steps leading to the re-establishment of the affected tissue or organ. The process of wound healing resembles fundamental processes like embryogenesis and tissue regeneration. All the stages in the wound healing process are tightly regulated and any sort of imbalance may lead to either non healing chronic ulcers or excessively healed hypertrophic scars. Diabetic wounds are also very tough to heal and in many cases they do not heal, ultimately resulting in the amputation of that body part. The non-healing property of diabetic wounds may be due to combined effect of intrinsic and extrinsic factors. In this review, we aimed to explore the steps involved in diabetic wound healing and compare it with the process of carcinogenesis. This review demonstrates that both carcinogenesis and the diabetic wound healing follow a similar path of latent healing in an abnormal exaggerated manner.

  16. Differential Apoptosis in Mucosal and Dermal Wound Healing

    Science.gov (United States)

    Johnson, Ariel; Francis, Marybeth; DiPietro, Luisa Ann

    2014-01-01

    Objectives: Dermal and mucosal healing are mechanistically similar. However, scarring and closure rates are dramatically improved in mucosal healing, possibly due to differences in apoptosis. Apoptosis, nature's preprogrammed form of cell death, occurs via two major pathways, extrinsic and intrinsic, which intersect at caspase3 (Casp3) cleavage and activation. The purpose of this experiment was to identify the predominant pathways of apoptosis in mucosal and dermal wound healing. Approach: Wounds (1 mm biopsy punch) were made in the dorsal skin (n=3) or tongue (n=3) of female Balb/C mice aged 6 weeks. Wounds were harvested at 6 h, 24 h, day 3 (D3), D5, D7, and D10. RNA was isolated and analyzed using real time reverse transcriptase–polymerase chain reaction. Expression levels for genes in the intrinsic and extrinsic apoptotic pathways were compared in dermal and mucosal wounds. Results: Compared to mucosal healing, dermal wounds exhibited significantly higher expression of Casp3 (at D5; phealing compared to skin. Conclusion: Expression patterns of key regulators of apoptosis in wound healing indicate that apoptosis occurs predominantly through the intrinsic pathway in the healing mucosa, but predominantly through the extrinsic pathway in the healing skin. The identification of differences in the apoptotic pathways in skin and mucosal wounds may allow the development of therapeutics to improve skin healing. PMID:25493209

  17. RNA-seq Transcriptional Profiling of an Arbuscular Mycorrhiza Provides Insights into Regulated and Coordinated Gene Expression in Lotus japonicus and Rhizophagus irregularis.

    Science.gov (United States)

    Handa, Yoshihiro; Nishide, Hiroyo; Takeda, Naoya; Suzuki, Yutaka; Kawaguchi, Masayoshi; Saito, Katsuharu

    2015-08-01

    Gene expression during arbuscular mycorrhizal development is highly orchestrated in both plants and arbuscular mycorrhizal fungi. To elucidate the gene expression profiles of the symbiotic association, we performed a digital gene expression analysis of Lotus japonicus and Rhizophagus irregularis using a HiSeq 2000 next-generation sequencer with a Cufflinks assembly and de novo transcriptome assembly. There were 3,641 genes differentially expressed during arbuscular mycorrhizal development in L. japonicus, approximately 80% of which were up-regulated. The up-regulated genes included secreted proteins, transporters, proteins involved in lipid and amino acid metabolism, ribosomes and histones. We also detected many genes that were differentially expressed in small-secreted peptides and transcription factors, which may be involved in signal transduction or transcription regulation during symbiosis. Co-regulated genes between arbuscular mycorrhizal and root nodule symbiosis were not particularly abundant, but transcripts encoding for membrane traffic-related proteins, transporters and iron transport-related proteins were found to be highly co-up-regulated. In transcripts of arbuscular mycorrhizal fungi, expansion of cytochrome P450 was observed, which may contribute to various metabolic pathways required to accommodate roots and soil. The comprehensive gene expression data of both plants and arbuscular mycorrhizal fungi provide a powerful platform for investigating the functional and molecular mechanisms underlying arbuscular mycorrhizal symbiosis. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  18. Silver nanoparticles enhance wound healing in zebrafish (Danio rerio).

    Science.gov (United States)

    Seo, Seung Beom; Dananjaya, S H S; Nikapitiya, Chamilani; Park, Bae Keun; Gooneratne, Ravi; Kim, Tae-Yoon; Lee, Jehee; Kim, Cheol-Hee; De Zoysa, Mahanama

    2017-09-01

    Silver nanoparticles (AgNPs) were successfully synthesized by a chemical reduction method, physico-chemically characterized and their effect on wound-healing activity in zebrafish was investigated. The prepared AgNPs were circular-shaped, water soluble with average diameter and zeta potential of 72.66 nm and -0.45 mv, respectively. Following the creation of a laser skin wound on zebrafish, the effect of AgNPs on wound-healing activity was tested by two methods, direct skin application (2 μg/wound) and immersion in a solution of AgNPs and water (50 μg/L). The zebrafish were followed for 20 days post-wounding (dpw) by visual observation of wound size, calculating wound healing percentage (WHP), and histological examination. Visually, both direct skin application and immersion AgNPs treatments displayed clear and faster wound closure at 5, 10 and 20 dpw compared to the controls, which was confirmed by 5 dpw histology data. At 5 dpw, WHP was highest in the AgNPs immersion group (36.6%) > AgNPs direct application group (23.7%) > controls (18.2%), showing that WHP was most effective in fish immersed in AgNPs solution. In general, exposure to AgNPs induced gene expression of selected wound-healing-related genes, namely, transforming growth factor (TGF-β), matrix metalloproteinase (MMP) -9 and -13, pro-inflammatory cytokines (IL-1β and TNF-α) and antioxidant enzymes (superoxide dismutase and catalase), which observed differentiation at 12 and 24 h against the control; but the results were not consistently significant, and many either reached basal levels or were down regulated at 5 dpw in the wounded muscle. These results suggest that AgNPs are effective in acceleration of wound healing and altered the expression of some wound-healing-related genes. However, the detailed mechanism of enhanced wound healing remains to be investigated in fish. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Nanoparticles for Fidgety Cell Movement and Enhanced Wound Healing.

    Science.gov (United States)

    Jozic, Ivan; Daunert, Sylvia; Tomic-Canic, Marjana; Pastar, Irena

    2015-09-01

    Complex spatiotemporal interaction of Rho GTPases with microtubules (MTs) and MT-associated proteins drives directed cellular migration. In this issue, Charafeddine et al. describe a role for a novel MT-severing enzyme, fidgetin-like 2 (FL2), in directional migration of keratinocytes and fibroblasts. FL2 normally localizes to the leading edge of the cell cortex where it shears MTs, thus dictating the size and distribution of focal adhesions by regulating cytoskeletal remodeling. Small interfering RNA (siRNA)-directed knockdown of FL2 increases cell migration and focal adhesion area in vitro through possible interaction with Rho GTPases. Efficient FL2 knockdown in murine wounds was achieved using nanoparticles as a siRNA delivery vehicle, and this resulted in enhanced wound closure in vivo. Effective siRNA nanoparticle targeting of MT-severing enzymes offers promise of controlled and targeted delivery that may maximize therapeutic success for patients with burn wounds and chronic wound disorders.

  20. Monitoring the Healing of Combat Wounds Using Raman Spectroscopic Mapping

    Science.gov (United States)

    2010-01-01

    ulated by twofold for impaired healing wounds compared with normal healing wounds, as well as for COL4A1 (type IV collagen a1). By the final debridement...Figure 3D), only COL18A1 shows an up-regulation in impaired heal- ing wounds compared with normal healing wounds, while COL1A1, COL3A1, COL4A1 , COL4A3...42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 F ol d C ha ng e in G en e E xp re ss io n A 4.2 0.6 COL18A1 COL1A1 COL3A1 COL4A1

  1. Incisional Negative Pressure Wound Therapy

    DEFF Research Database (Denmark)

    Hyldig, Nana

    the rate of surgical wound infection and wound exudate post-caesarean and that wound infection had a negative impact on quality of life one month after surgery. Alongside the clinical trial, a trial-based cost-effectiveness analysis demonstrated that the treatment is cost-effective in a high......Women with a pre-gestational body mass index (BMI) above 30 kg/m2 giving birth by caesarean section are at high risk of surgical wound infection compared with women with a BMI below 30 kg/m2. Incisional Negative Pressure Wound Therapy (iNPWT) is one strategy to reduce the rate of surgical wound...... infection. However, the treatment is relatively costly compared to standard postoperative dressings and thus it was important to consider the rationale for using iNPWT before introducing the treatment in a clinical setting. This thesis assesses the current evidence of whether iNPWT reduces post...

  2. The management of perineal wounds

    Directory of Open Access Journals (Sweden)

    Ramesh k Sharma

    2012-01-01

    Full Text Available Management of perineal wounds can be very frustrating as these invariably get contaminated from the ano-genital tracts. Moreover, the apparent skin defect may be associated with a significant three dimensional dead space in the pelvic region. Such wounds are likely to become chronic and recalcitrant if appropriate wound management is not instituted in a timely manner. These wounds usually result after tumor excision, following trauma or as a result of infective pathologies like hideradenitis suppurativa or following thermal burns. Many options are available for management of perineal wounds and these have been discussed with illustrative case examples. A review of literature has been done for listing commonly instituted options for management of the wounds in perineum.

  3. Reconstructive challenges in war wounds

    OpenAIRE

    Bhandari, Prem Singh; Maurya, Sanjay; Mukherjee, Mrinal Kanti

    2012-01-01

    War wounds are devastating with extensive soft tissue and osseous destruction and heavy contamination. War casualties generally reach the reconstructive surgery centre after a delayed period due to additional injuries to the vital organs. This delay in their transfer to a tertiary care centre is responsible for progressive deterioration in wound conditions. In the prevailing circumstances, a majority of war wounds undergo delayed reconstruction, after a series of debridements. In the recent m...

  4. Botanical drug puerarin coordinates with nerve growth factor in the regulation of neuronal survival and neuritogenesis via activating ERK1/2 and PI3K/Akt signaling pathways in the neurite extension process.

    Science.gov (United States)

    Zhao, Jia; Cheng, Yuan-Yuan; Fan, Wen; Yang, Chuan-Bin; Ye, Shui-Fen; Cui, Wei; Wei, Wei; Lao, Li-Xing; Cai, Jing; Han, Yi-Fan; Rong, Jian-Hui

    2015-01-01

    Nerve growth factor (NGF) regulates neuronal survival and differentiation by activating extracellular signal-regulated-kinases (ERK) 1/2 and phosphoinositide-3-kinase (PI3K)/Akt pathways in two distinct processes: latency process and neurite extension process. This study was designed to investigate whether botanical drug C-glucosylated isoflavone puerarin coordinates with NGF to regulate neuritogenesis via activating ERK1/2 and PI3K/Akt in neurite extension process. We investigated the neuroprotective and neurotrophic activities of puerarin in MPTP-lesioned mice and dopaminergic PC12 cells. The effects of puerarin on ERK1/2, Akt, Nrf2, and HO-1 were assessed by Western blotting. The neurite outgrowth was assayed by neurite outgrowth staining kit. Puerarin protected dopaminergic cells and ameliorated the behavioral impairments in MPTP-lesioned mice. Puerarin potentiated the effect of NGF on neuritogenesis in PC12 cells by >10-fold. Mechanistic studies revealed: (1) puerarin rapidly activated ERK1/2 and Akt, leading to the activation of Nrf2/heme oxygenase-1 (HO-1) pathways; (2) ERK1/2, PI3K/Akt, and HO-1 inhibitors attenuated the neuritogenic activity of puerarin. Notably, puerarin enhanced NGF-induced neuritogenesis in a timing-dependent manner. Puerarin effectively coordinated with NGF to stimulate neuritogenesis via activating ERK1/2 and PI3K/Akt pathways in neurite extension process. These results demonstrated a general mechanism supporting the therapeutic application of puerarin-related compounds in neurodegenerative diseases. © 2014 John Wiley & Sons Ltd.

  5. [Interobserver variation in wound assessments].

    Science.gov (United States)

    Lorentzen, H F; Gottrup, F

    1998-05-25

    Agreement in describing a chronic leg ulcer is pivotal in identifying and treating impediments to the healing process. Six nurses and one doctor without special experience with wound healing registered wound related diagnoses for a five month period. On average each patient was seen by three observers yielding 270 registrations. Agreement beyond chance (global kappa) showed poor to moderate agreement. Agreement was best for the yellow or malodorous wound and lowest for cellulitis, hypergranulation and peripheral pulses. This emphasizes the importance of allocating wound treatment to specialist departments with access to paraclinical investigations.

  6. The expression of the hydroxyproline-rich glycopeptide systemin precursor A in response to (a)biotic stress and elicitors is indicative of its role in the regulation of the wound response in tobacco (Nicotiana tabacum L.).

    Science.gov (United States)

    Rocha-Granados, Carmen del María; Sánchez-Hernández, Carlos; Sánchez-Hernández, Carla; Martínez-Gallardo, Norma Angélica; Ochoa-Alejo, Neftalí; Délano-Frier, John Paul

    2005-11-01

    Two hydroxyproline-rich glycopeptide systemin (TobHS) precursor proteins known as preproTobHypSys-A and B were recently discovered in tobacco (Nicotiana tabacum L.) [Pearce et al. in Nature 411:817-820, 2001]. In this work, the effect of elicitors, insect damage, and abiotic stress on the expression of preproTobHypSys-A ppTobHS-A) in tobacco plants was evaluated. Foliar application of methyl jasmonate preferentially induced the systemic expression of ppTobHS-A in leaves phyllotactically one position above-treated leaves. Abscisic acid strongly induced ppTobHS-A, but water-stress did not. Mechanical wound-induction of ppTobHS-A in young plantlets was rapidly (1 h) and simultaneously detected in wounded and upper unwounded leaves, whereas in older plants induction was slow (12 h) and localized. ppTobHS-A was induced in plants infested with Bemisia tabaci or damaged by herbivory with Manduca sexta larvae. Compared to mechanical wounding, larval herbivory induced a stronger and more stable expression of ppTobHS-A. Moreover, exposure to Manduca-damaged plants induced its expression in neighboring intact plants. In most treatments, the expression patterns of ppTobHS-A coincided with those of selected wound-responsive (WR) genes (e.g., PIOX, NtPI-I, TPI). This correlation was tighter in the wounded and MeJA-treated leaves, whereas in distal, undamaged leaves, it appeared to depend on the type of WR gene examined and on the type of damage sustained by the plant. These results are consistent with the perceived role of the TobHS in defense signaling.

  7. The coordinated roles of miR-26a and miR-30c in regulating TGFβ1-induced epithelial-to-mesenchymal transition in diabetic nephropathy

    DEFF Research Database (Denmark)

    Zheng, Zongji; Guan, Meiping; Jia, Yijie

    2016-01-01

    ameliorated TGFβ1-induced EMT in NRK-52E cells. Co-silencing of miR-26a and miR-30c exhibited the opposite effect. Moreover, miR-26a and miR-30c co-silenced CTGF to decrease ERK1/2 and p38 MAPK activation. Furthermore, miR-26a was up-regulated in urinary extracellular vesicles of diabetic nephropathy patients...

  8. p38 MAPK inhibition reduces diabetes-induced impairment of wound healing

    Directory of Open Access Journals (Sweden)

    Satyanarayana Medicherla

    2009-06-01

    Full Text Available Satyanarayana Medicherla1, Scott Wadsworth2, Breda Cullen3, Derek Silcock3, Jing Y Ma1, Ruban Mangadu1, Irene Kerr1, Sarvajit Chakravarty1, Gregory L Luedtke1, Sundeep Dugar1, Andrew A Protter1, Linda S Higgins11Scios Inc., Fremont, CA, USA; 2Center for Biomaterials and Advanced Technologies, Somerville, NJ, USA; 3Johnson & Johnson Wound Management, Gargrave, UKAbstract: In healthy tissue, a wound initiates an inflammatory response characterized by the presence of a hematoma, infiltration of inflammatory cells into the wound and, eventually, wound healing. In pathological conditions like diabetes mellitus, wound healing is impaired by the presence of chronic nonresolving inflammation. p38 mitogen-activated protein kinase (MAPK inhibitors have demonstrated anti-inflammatory effects, primarily by inhibiting the expression of inflammatory cytokines and regulating cellular traffic into wounds. The db/db mouse model of type 2 diabetes was used to characterize the time course of expression of activated p38 during impaired wound healing. The p38α-selective inhibitor, SCIO-469, was applied topically and effects on p38 activation and on wound healing were evaluated. A topical dressing used clinically, PromogranTM, was used as a comparator. In this study, we established that p38 is phosphorylated on Days 1 to 7 post-wounding in db/db mice. Further, we demonstrated that SCIO-469, at a dose of 10 µg/wound, had a positive effect on wound contraction, granulation tissue formation, and re-epithelialization, and also increased wound maturity during healing. These effects were similar to or greater than those observed with PromogranTM. These results suggest a novel approach to prophylactic and therapeutic management of chronic wounds associated with diabetes or other conditions in which healing is impaired.Keywords: p38 MAPK ihibition, diabetic wound healing, db/db mouse, nonresolving healing, PromogranTM

  9. IRF-3, IRF-5, and IRF-7 coordinately regulate the type I IFN response in myeloid dendritic cells downstream of MAVS signaling.

    Directory of Open Access Journals (Sweden)

    Helen M Lazear

    2013-01-01

    Full Text Available Although the transcription factors IRF-3 and IRF-7 are considered master regulators of type I interferon (IFN induction and IFN stimulated gene (ISG expression, Irf3(-/-×Irf7(-/- double knockout (DKO myeloid dendritic cells (mDC produce relatively normal levels of IFN-β after viral infection. We generated Irf3(-/-×Irf5(-/-×Irf7(-/- triple knockout (TKO mice to test whether IRF-5 was the source of the residual induction of IFN-β and ISGs in mDCs. In pathogenesis studies with two unrelated positive-sense RNA viruses (West Nile virus (WNV and murine norovirus, TKO mice succumbed at rates greater than DKO mice and equal to or approaching those of mice lacking the type I IFN receptor (Ifnar(-/-. In ex vivo studies, after WNV infection or exposure to Toll-like receptor agonists, TKO mDCs failed to produce IFN-β or express ISGs. In contrast, this response was sustained in TKO macrophages following WNV infection. To define IRF-regulated gene signatures, we performed microarray analysis on WNV-infected mDC from wild type (WT, DKO, TKO, or Ifnar(-/- mice, as well as from mice lacking the RIG-I like receptor adaptor protein MAVS. Whereas the gene induction pattern in DKO mDC was similar to WT cells, remarkably, almost no ISG induction was detected in TKO or Mavs(-/- mDC. The relative equivalence of TKO and Mavs(-/- responses suggested that MAVS dominantly regulates ISG induction in mDC. Moreover, we showed that MAVS-dependent induction of ISGs can occur through an IRF-5-dependent yet IRF-3 and IRF-7-independent pathway. Our results establish IRF-3, -5, and -7 as the key transcription factors responsible for mediating the type I IFN and ISG response in mDC during WNV infection and suggest a novel signaling link between MAVS and IRF-5.

  10. Tilapia Piscidin 4 (TP4 Stimulates Cell Proliferation and Wound Closure in MRSA-Infected Wounds in Mice

    Directory of Open Access Journals (Sweden)

    Hang-Ning Huang

    2015-05-01

    Full Text Available Antimicrobial peptides (AMPs are endogenous antibiotics that directly affect microorganisms, and also have a variety of receptor-mediated functions. One such AMP, Tilapia piscidin 4 (TP4, was isolated from Nile tilapia (Oreochromis niloticus; TP4 has antibacterial effects and regulates the innate immune system. The aim of the present study was to characterize the role of TP4 in the regulation of wound closure in mice and proliferation of a keratinocyte cell line (HaCaT and fibroblast cell line (Hs-68. In vitro, TP4 stimulated cell proliferation and activated collagen I, collagen III, and keratinocyte growth factor (KGF gene expression in Hs-68 cells, which induces keratin production by HaCaT cells. This effect was detectable at TP4 concentrations of 6.25 µg/mL in both cell lines. In vivo, TP4 was found to be highly effective at combating peritonitis and wound infection caused by MRSA in mouse models, without inducing adverse behavioral effects or liver or kidney toxicity. Taken together, our results indicate that TP4 enhances the survival rate of mice infected with the bacterial pathogen MRSA through both antimicrobial and wound closure activities mediated by epidermal growth factor (EGF, transforming growth factor (TGF, and vascular endothelial growth factor (VEGF. The peptide is likely involved in antibacterial processes and regulation of tissue homeostasis in infected wounds in mice. Overall, these results suggest that TP4 may be suitable for development as a novel topical agent for wound dressing.

  11. Incisional Negative Pressure Wound Therapy

    DEFF Research Database (Denmark)

    Hyldig, Nana; Vinter, Christina Anne; Bille, Camilla

    Background: Obese women undergoing caesarean section are at increased risk of surgical wound complications, which may lead to delayed recovery, pain, reduced quality of life, and increased health care cost. The aim of this study is to evaluate the effect of incisional Negative Pressure Wound...

  12. Critical Advances in Wound Care

    Science.gov (United States)

    2011-01-24

    Nutritionist  Infectious disease specialist  Administrator  Physical and occupational therapist  Nurse practitioner Wound clinic manager...of high AKA amputations with accompanying fungal infections – Need for local therapy • Wound VAC™ Instill® therapy • Dakin’s irrigation solution

  13. Ribosomal protein-Mdm2-p53 pathway coordinates nutrient stress with lipid metabolism by regulating MCD and promoting fatty acid oxidation.

    Science.gov (United States)

    Liu, Yong; He, Yizhou; Jin, Aiwen; Tikunov, Andrey P; Zhou, Lishi; Tollini, Laura A; Leslie, Patrick; Kim, Tae-Hyung; Li, Lei O; Coleman, Rosalind A; Gu, Zhennan; Chen, Yong Q; Macdonald, Jeffrey M; Graves, Lee M; Zhang, Yanping

    2014-06-10

    The tumor suppressor p53 has recently been shown to regulate energy metabolism through multiple mechanisms. However, the in vivo signaling pathways related to p53-mediated metabolic regulation remain largely uncharacterized. By using mice bearing a single amino acid substitution at cysteine residue 305 of mouse double minute 2 (Mdm2(C305F)), which renders Mdm2 deficient in binding ribosomal proteins (RPs) RPL11 and RPL5, we show that the RP-Mdm2-p53 signaling pathway is critical for sensing nutrient deprivation and maintaining liver lipid homeostasis. Although the Mdm2(C305F) mutation does not significantly affect growth and development in mice, this mutation promotes fat accumulation under normal feeding conditions and hepatosteatosis under acute fasting conditions. We show that nutrient deprivation inhibits rRNA biosynthesis, increases RP-Mdm2 interaction, and induces p53-mediated transactivation of malonyl-CoA decarboxylase (MCD), which catalyzes the degradation of malonyl-CoA to acetyl-CoA, thus modulating lipid partitioning. Fasted Mdm2(C305F) mice demonstrate attenuated MCD induction and enhanced malonyl-CoA accumulation in addition to decreased oxidative respiration and increased fatty acid accumulation in the liver. Thus, the RP-Mdm2-p53 pathway appears to function as an endogenous sensor responsible for stimulating fatty acid oxidation in response to nutrient depletion.

  14. Antimicrobial stewardship in wound care

    DEFF Research Database (Denmark)

    Lipsky, Benjamin A; Dryden, Matthew; Gottrup, Finn

    2016-01-01

    BACKGROUND: With the growing global problem of antibiotic resistance it is crucial that clinicians use antibiotics wisely, which largely means following the principles of antimicrobial stewardship (AMS). Treatment of various types of wounds is one of the more common reasons for prescribing...... antibiotics. OBJECTIVES: This guidance document is aimed at providing clinicians an understanding of: the basic principles of why AMS is important in caring for patients with infected wounds; who should be involved in AMS; and how to conduct AMS for patients with infected wounds. METHODS: We assembled a group...... of experts in infectious diseases/clinical microbiology (from the British Society for Antimicrobial Chemotherapy) and wound management (from the European Wound Management Association) who, after thoroughly reviewing the available literature and holding teleconferences, jointly produced this guidance document...

  15. Surgical Management of Chronic Wounds.

    Science.gov (United States)

    Johnston, Benjamin R; Ha, Austin Y; Kwan, Daniel

    2016-02-01

    In this article, we outline the important role the surgeon plays in the management of chronic wounds. Debridement and washout are required for grossly infected wounds and necrotizing soft tissue infections. Cutaneous cancers such as squamous cell carcinomas may contribute to chronic wounds and vice versa; if diagnosed, these should be treated with wide local excision. Arterial, venous, and even lymphatic flows can be restored in select cases to enhance delivery of nutrients and removal of metabolic waste and promote wound healing. In cases where vital structures, such as bones, joints, tendons, and nerves, are exposed, vascularized tissue transfers are often required. These tissue transfers can be local or remote, the latter of which necessitates anastomoses of arteries and veins. Pressure sores are managed by relieving pressure, treating acute trauma or infection, and using rotation fasciocutaneous flaps. Lastly, the surgeon must always consider the possibility of osteomyelitis and retained foreign body as etiology for chronic wounds.

  16. Picroliv accelerates epithelialization and angiogenesis in rat wounds.

    Science.gov (United States)

    Singh, Anoop K; Sharma, Anuj; Warren, James; Madhavan, Subhashree; Steele, Keith; RajeshKumar, N V; Thangapazham, Rajesh L; Sharma, Shekhar C; Kulshreshtha, Dinesh K; Gaddipati, Jaya; Maheshwari, Radha K

    2007-03-01

    Tissue repair and wound healing are complex processes that involve inflammation, granulation and tissue remodeling. Angiogenesis plays a central role in wound healing. Earlier, we have shown that picroliv, a natural product obtained from the roots of Picrorhiza kurrooa, up-regulates the expression of vascular endothelial growth factor in human umbilical vein endothelial cells and of insulin-like growth factor in rats during hypoxia. 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. We also investigated punch wound healing on days 4 and 7 after wounding by histology, morphometry and collagenization. The data showed improved re-epithelialization, neovascularization and migration of various cells such as endothelial, dermal myofibroblasts and fibroblasts into the wound bed after picroliv treatment. Immunohistochemical localization showed increased VEGF and alpha smooth muscle actin staining consistent with an increased number of microvessels in granulation tissue. These findings suggest that picroliv could be developed as a therapeutic angiogenic agent for the restoration of the blood supply in diseases involving inadequate blood supply such as limb ischemia, ischemic myocardium and wound healing.

  17. Microbial symbionts accelerate wound healing via the neuropeptide hormone oxytocin.

    Directory of Open Access Journals (Sweden)

    Theofilos Poutahidis

    Full Text Available Wound healing capability is inextricably linked with diverse aspects of physical fitness ranging from recovery after minor injuries and surgery to diabetes and some types of cancer. Impact of the microbiome upon the mammalian wound healing process is poorly understood. We discover that supplementing the gut microbiome with lactic acid microbes in drinking water accelerates the wound-healing process to occur in half the time required for matched control animals. Further, we find that Lactobacillus reuteri enhances wound-healing properties through up-regulation of the neuropeptide hormone oxytocin, a factor integral in social bonding and reproduction, by a vagus nerve-mediated pathway. Bacteria-triggered oxytocin serves to activate host CD4+Foxp3+CD25+ immune T regulatory cells conveying transplantable wound healing capacity to naive Rag2-deficient animals. This study determined oxytocin to be a novel component of a multi-directional gut microbe-brain-immune axis, with wound-healing capability as a previously unrecognized output of this axis. We also provide experimental evidence to support long-standing medical traditions associating diet, social practices, and the immune system with efficient recovery after injury, sustained good health, and longevity.

  18. Estrogen receptor alpha and nuclear factor Y coordinately regulate the transcription of the SUMO-conjugating UBC9 gene in MCF-7 breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Shibo Ying

    Full Text Available UBC9 encodes a protein that conjugates small ubiquitin-related modifier (SUMO to target proteins thereby changing their functions. Recently, it was noted that UBC9 expression and activity play a role in breast tumorigenesis and response to anticancer drugs. However, the underlying mechanism is poorly understood. To investigate the transcriptional regulation of the UBC9 gene, we identified and characterized its promoter and cis-elements. Promoter activity was tested using luciferase reporter assays. The binding of transcription factors to the promoter was detected by chromatin immunoprecipitation (ChIP, and their functional role was confirmed by siRNA knockdown. UBC9 mRNA and protein levels were measured by quantitative reverse transcription PCR and Western blot analysis, respectively. An increased expression of UBC9 mRNA and protein was found in MCF-7 breast cancer cells treated with 17β-estradiol (E2. Analysis of various deletion mutants revealed a 137 bp fragment upstream of the transcription initiation site to be sufficient for reporter gene transcription. Mutations of putative estrogen receptor α (ER-α (one imperfect estrogen response element, ERE and/or nuclear factor Y (NF-Y binding sites (two CCAAT boxes markedly reduced promoter activity. Similar results were obtained in ER-negative MDA-MB-231 cells except that the ERE mutation did not affect promoter activity. Additionally, promoter activity was stimulated upon E2 treatment and overexpression of ER-α or NF-YA in MCF-7 cells. ChIP confirmed direct binding of both transcription factors to the UBC9 promoter in vivo. Furthermore, UBC9 expression was diminished by ER-α and NF-Y siRNAs on the mRNA and protein levels. In conclusion, we identified the proximal UBC9 promoter and provided evidence that ER-α and NF-Y regulate UBC9 expression on the transcriptional level in response to E2 in MCF-7 cells. These findings may contribute to a better understanding of the regulation of UBC9 in ER

  19. Estrogen receptor alpha and nuclear factor Y coordinately regulate the transcription of the SUMO-conjugating UBC9 gene in MCF-7 breast cancer cells.

    Science.gov (United States)

    Ying, Shibo; Dünnebier, Thomas; Si, Jing; Hamann, Ute

    2013-01-01

    UBC9 encodes a protein that conjugates small ubiquitin-related modifier (SUMO) to target proteins thereby changing their functions. Recently, it was noted that UBC9 expression and activity play a role in breast tumorigenesis and response to anticancer drugs. However, the underlying mechanism is poorly understood. To investigate the transcriptional regulation of the UBC9 gene, we identified and characterized its promoter and cis-elements. Promoter activity was tested using luciferase reporter assays. The binding of transcription factors to the promoter was detected by chromatin immunoprecipitation (ChIP), and their functional role was confirmed by siRNA knockdown. UBC9 mRNA and protein levels were measured by quantitative reverse transcription PCR and Western blot analysis, respectively. An increased expression of UBC9 mRNA and protein was found in MCF-7 breast cancer cells treated with 17β-estradiol (E2). Analysis of various deletion mutants revealed a 137 bp fragment upstream of the transcription initiation site to be sufficient for reporter gene transcription. Mutations of putative estrogen receptor α (ER-α) (one imperfect estrogen response element, ERE) and/or nuclear factor Y (NF-Y) binding sites (two CCAAT boxes) markedly reduced promoter activity. Similar results were obtained in ER-negative MDA-MB-231 cells except that the ERE mutation did not affect promoter activity. Additionally, promoter activity was stimulated upon E2 treatment and overexpression of ER-α or NF-YA in MCF-7 cells. ChIP confirmed direct binding of both transcription factors to the UBC9 promoter in vivo. Furthermore, UBC9 expression was diminished by ER-α and NF-Y siRNAs on the mRNA and protein levels. In conclusion, we identified the proximal UBC9 promoter and provided evidence that ER-α and NF-Y regulate UBC9 expression on the transcriptional level in response to E2 in MCF-7 cells. These findings may contribute to a better understanding of the regulation of UBC9 in ER

  20. DDX3 directly regulates TRAF3 ubiquitination and acts as a scaffold to co-ordinate assembly of signalling complexes downstream from MAVS.

    Science.gov (United States)

    Gu, Lili; Fullam, Anthony; McCormack, Niamh; Höhn, Yvette; Schröder, Martina

    2017-02-15

    The human DEAD-box helicase 3 (DDX3) has been shown to contribute to type I interferon (IFN) induction downstream from antiviral pattern recognition receptors. It binds to TANK-binding kinase 1 and IκB-kinase-ε (IKKε), the two key kinases mediating activation of IFN regulatory factor (IRF) 3 and IRF7. We previously demonstrated that DDX3 facilitates IKKε activation downstream from RIG-I and then links the activated kinase to IRF3. In the present study, we probed the interactions between DDX3 and other key signalling molecules in the RIG-I pathway and identified a novel direct interaction between DDX3 and TNF receptor-associated factor 3 (TRAF3) mediated by a TRAF-interaction motif in the N-terminus of DDX3, which was required for TRAF3 ubiquitination. Interestingly, we observed two waves of K63-linked TRAF3 ubiquitination following RIG-I activation by Sendai virus (SeV) infection, both of which were suppressed by DDX3 knockdown. We also investigated the spatiotemporal formation of endogenous downstream signalling complexes containing the mitochondrial antiviral signalling (MAVS) adaptor, DDX3, IκB-kinase-ε (IKKε), TRAF3 and IRF3. DDX3 was recruited to MAVS early after SeV infection, suggesting that it might mediate subsequent recruitment of other molecules. Indeed, knockdown of DDX3 prevented the formation of TRAF3-MAVS and TRAF3-IKKε complexes. Based on our data, we propose that early TRAF3 ubiquitination is required for the formation of a stable MAVS-TRAF3 complex, while the second wave of TRAF3 ubiquitination mediates IRF3 recruitment and activation. Our study characterises DDX3 as a multifunctional adaptor molecule that co-ordinates assembly of different TRAF3, IKKε and IRF3-containing signalling complexes downstream from MAVS. Additionally, it provides novel insights into the role of TRAF3 in RIG-I signalling. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  1. Tight Junction Proteins Claudin-1 and Occludin Are Important for Cutaneous Wound Healing.

    Science.gov (United States)

    Volksdorf, Thomas; Heilmann, Janina; Eming, Sabine A; Schawjinski, Kathrin; Zorn-Kruppa, Michaela; Ueck, Christopher; Vidal-Y-Sy, Sabine; Windhorst, Sabine; Jücker, Manfred; Moll, Ingrid; Brandner, Johanna M

    2017-06-01

    Tight junction (TJ) proteins are known to be involved in proliferation and differentiation. These processes are essential for normal skin wound healing. Here, we investigated the TJ proteins claudin-1 and occludin in ex vivo skin wound healing models and tissue samples of acute and chronic human wounds and observed major differences in localization/expression of these proteins, with chronic wounds often showing a loss of the proteins at the wound margins and/or in the regenerating epidermis. Knockdown experiments in primary human keratinocytes showed that decreased claudin-1 expression resulted in significantly impaired scratch wound healing, with delayed migration and reduced proliferation. Activation of AKT pathway was significantly attenuated after claudin-1 knockdown, and protein levels of extracellular signal-related kinase 1/2 were reduced. For occludin, down-regulation had no impact on wound healing in normal scratch assays, but after subjecting the cells to mechanical stress, which is normally present in wounds, wound healing was impaired. For both proteins we show that most of these actions are independent from the formation of barrier-forming TJ structures, thus demonstrating nonbarrier-related functions of TJ proteins in the skin. However, for claudin-1 effects on scratch wound healing were more pronounced when TJs could form. Together, our findings provide evidence for a role of claudin-1 and occludin in epidermal regeneration with potential clinical importance. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  2. Automatic wound infection interpretation for postoperative wound image

    Science.gov (United States)

    Hsu, Jui-Tse; Ho, Te-Wei; Shih, Hsueh-Fu; Chang, Chun-Che; Lai, Feipei; Wu, Jin-Ming

    2017-02-01

    With the growing demand for more efficient wound care after surgery, there is a necessity to develop a machine learning based image analysis approach to reduce the burden for health care professionals. The aim of this study was to propose a novel approach to recognize wound infection on the postsurgical site. Firstly, we proposed an optimal clustering method based on unimodal-rosin threshold algorithm to extract the feature points from a potential wound area into clusters for regions of interest (ROI). Each ROI was regarded as a suture site of the wound area. The automatic infection interpretation based on the support vector machine is available to assist physicians doing decision-making in clinical practice. According to clinical physicians' judgment criteria and the international guidelines for wound infection interpretation, we defined infection detector modules as the following: (1) Swelling Detector, (2) Blood Region Detector, (3) Infected Detector, and (4) Tissue Necrosis Detector. To validate the capability of the proposed system, a retrospective study using the confirmation wound pictures that were used for diagnosis by surgical physicians as the gold standard was conducted to verify the classification models. Currently, through cross validation of 42 wound images, our classifiers achieved 95.23% accuracy, 93.33% sensitivity, 100% specificity, and 100% positive predictive value. We believe this ability could help medical practitioners in decision making in clinical practice.

  3. Collecting and measuring wound exudate biochemical mediators in surgical wounds.

    Science.gov (United States)

    Carvalho, Brendan; Clark, David J; Yeomans, David; Angst, Martin S

    2012-10-20

    We describe a methodology by which we are able to collect and measure biochemical inflammatory and nociceptive mediators at the surgical wound site. Collecting site-specific biochemical markers is important to understand the relationship between levels in serum and surgical wound, determine any associations between mediator release, pain, analgesic use and other outcomes of interest, and evaluate the effect of systemic and peripheral drug administration on surgical wound biochemistry. This methodology has been applied to healthy women undergoing elective cesarean delivery with spinal anesthesia. We have measured wound exudate and serum mediators at the same time intervals as patient's pain scores and analgesics consumption for up to 48 hours post-cesarean delivery. Using this methodology we have been able to detect various biochemical mediators including nerve growth factor (NGF), prostaglandin E2 (PG-E2) substance P, IL-1β, IL-2, IL-4, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, TNFα, INFγ, G-CSF, GM-CSF, MCP-1 and MIP-1β. Studies applying this human surgical wound bioassay have found no correlations between wound and serum cytokine concentrations or their time-release profile (J Pain. 2008; 9(7):650-7).(1) We also documented the utility of the technique to identify drug-mediated changes in wound cytokine content.

  4. Coordinated Multi-Objective Control of Regulating Resources in Multi-Area Power Systems with Large Penetration of Wind Power Generation

    DEFF Research Database (Denmark)

    Nyeng, Preben; Yang, Bo; Ma, Jian

    2008-01-01

    This paper describes a control algorithm for a Wide Area Energy Storage and Management System (WAEMS). The WAEMS is designed to meet the demand for fast, accurate and reliable regulation services in multi-area power systems with a significant share of wind power and other intermittent generation....... The means are utilization of flywheel energy storage units, hydro power generation, and energy exchange among the participating control areas. The objective of the control algorithm is to respond to the control signals from the different system operators, whilst optimizing the hydro power plant operation...... by reducing the tear and wear on the mechanical parts and improving the energy efficiency of the plant. The performance of the WAEMS is simulated using a mathematical model, including hydro power plant and flywheel energy storage models. ACE measurements from the California ISO and Bonneville Power...

  5. Coordinated regulation by two VPS9 domain-containing guanine nucleotide exchange factors in small GTPase Rab5 signaling pathways in fission yeast

    Energy Technology Data Exchange (ETDEWEB)

    Tsukamoto, Yuta [Department of Biology, Graduate School of Science, Kobe University, 1-1 Rokkodai-cho, Nada, Kobe 657-8501 (Japan); Kagiwada, Satoshi [Department of Biological Sciences, Faculty of Science, Nara Women' s University, Kitauoyanishi-machi, Nara 630-8506 (Japan); Shimazu, Sayuri [Center for Supports to Research and Education Activities, Kobe University, 1-1 Rokkodai-cho, Nada, Kobe 657-8501 (Japan); Takegawa, Kaoru [Department of Bioscience and Biotechnology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581 (Japan); Noguchi, Tetsuko [Department of Biological Sciences, Faculty of Science, Nara Women' s University, Kitauoyanishi-machi, Nara 630-8506 (Japan); Miyamoto, Masaaki, E-mail: miya@kobe-u.ac.jp [Department of Biology, Graduate School of Science, Kobe University, 1-1 Rokkodai-cho, Nada, Kobe 657-8501 (Japan); Center for Supports to Research and Education Activities, Kobe University, 1-1 Rokkodai-cho, Nada, Kobe 657-8501 (Japan)

    2015-03-20

    The small GTPase Rab5 is reported to regulate various cellular functions, such as vesicular transport and endocytosis. VPS9 domain-containing proteins are thought to activate Rab5(s) by their guanine-nucleotide exchange activities. Numerous VPS9 proteins have been identified and are structurally conserved from yeast to mammalian cells. However, the functional relationships among VPS9 proteins in cells remain unclear. Only one Rab5 and two VPS9 proteins were identified in the Schizosaccharomyces pombe genome. Here, we examined the cellular function of two VPS9 proteins and the relationship between these proteins in cellular functions. Vps901-GFP and Vps902-GFP exhibited dotted signals in vegetative and differentiated cells. vps901 deletion mutant (Δvps901) cells exhibited a phenotype deficient in the mating process and responses to high concentrations of ions, such as calcium and metals, and Δvps901Δvps902 double mutant cells exhibited round cell shapes similar to ypt5-909 (Rab5 mutant allele) cells. Deletion of both vps901 and vps902 genes completely abolished the mating process and responses to various stresses. A lack of vacuole formation and aberrant inner cell membrane structures were also observed in Δvps901Δvps902 cells by electron microscopy. These data strongly suggest that Vps901 and Vps902 are cooperatively involved in the regulation of cellular functions, such as cell morphology, sexual development, response to ion stresses, and vacuole formation, via Rab5 signaling pathways in fission yeast cells. - Highlights: • Roles of Rab5 activator VPS9 proteins in cellular functions. • Cooperation between VPS9 proteins in Rab5 signaling pathway. • Roles of each VPS9 protein in Rab5 signaling pathway are discussed.

  6. Wound repair in Pocillopora

    Science.gov (United States)

    Rodríguez-Villalobos, Jenny Carolina; Work, Thierry M.; Calderon-Aguileraa, Luis Eduardo

    2016-01-01

    Corals routinely lose tissue due to causes ranging from predation to disease. Tissue healing and regeneration are fundamental to the normal functioning of corals, yet we know little about this process. We described the microscopic morphology of wound repair in Pocillopora damicornis. Tissue was removed by airbrushing fragments from three healthy colonies, and these were monitored daily at the gross and microscopic level for 40 days. Grossly, corals healed by Day 30, but repigmentation was not evident at the end of the study (40 d). On histology, from Day 8 onwards, tissues at the lesion site were microscopically indistinguishable from adjacent normal tissues with evidence of zooxanthellae in gastrodermis. Inflammation was not evident. P. damicornis manifested a unique mode of regeneration involving projections of cell-covered mesoglea from the surface body wall that anastomosed to form gastrovascular canals.

  7. Matrix metalloproteinase inhibition delays wound healing and blocks the latent transforming growth factor-beta1-promoted myofibroblast formation and function

    DEFF Research Database (Denmark)

    Mirastschijski, Ursula; Schnabel, Reinhild; Claes, Juliane

    2010-01-01

    The ability to regulate wound contraction is critical for wound healing as well as for pathological contractures. Matrix metalloproteinases (MMPs) have been demonstrated to be obligatory for normal wound healing. This study examined the effect that the broad-spectrum MMP inhibitor BB-94 has when...

  8. Redefining the Chronic-Wound Microbiome: Fungal Communities Are Prevalent, Dynamic, and Associated with Delayed Healing.

    Science.gov (United States)

    Kalan, Lindsay; Loesche, Michael; Hodkinson, Brendan P; Heilmann, Kristopher; Ruthel, Gordon; Gardner, Sue E; Grice, Elizabeth A

    2016-09-06

    Chronic nonhealing wounds have been heralded as a silent epidemic, causing significant morbidity and mortality especially in elderly, diabetic, and obese populations. Polymicrobial biofilms in the wound bed are hypothesized to disrupt the highly coordinated and sequential events of cutaneous healing. Both culture-dependent and -independent studies of the chronic-wound microbiome have almost exclusively focused on bacteria, omitting what we hypothesize are important fungal contributions to impaired healing and the development of complications. Here we show for the first time that fungal communities (the mycobiome) in chronic wounds are predictive of healing time, associated with poor outcomes, and form mixed fungal-bacterial biofilms. We longitudinally profiled 100, nonhealing diabetic-foot ulcers with high-throughput sequencing of the pan-fungal internal transcribed spacer 1 (ITS1) locus, estimating that up to 80% of wounds contain fungi, whereas cultures performed in parallel captured only 5% of colonized wounds. The "mycobiome" was highly heterogeneous over time and between subjects. Fungal diversity increased with antibiotic administration and onset of a clinical complication. The proportions of the phylum Ascomycota were significantly greater (P = 0.015) at the beginning of the study in wounds that took >8 weeks to heal. Wound necrosis was distinctly associated with pathogenic fungal species, while taxa identified as allergenic filamentous fungi were associated with low levels of systemic inflammation. Directed culturing of wounds stably colonized by pathogens revealed that interkingdom biofilms formed between yeasts and coisolated bacteria. Combined, our analyses provide enhanced resolution of the mycobiome during impaired wound healing, its role in chronic disease, and impact on clinical outcomes. Wounds are an underappreciated but serious complication for a diverse spectrum of diseases. High-risk groups, such as persons with diabetes, have a 25% lifetime

  9. Gunshot wounds: epidemiology, wound ballistics, and soft-tissue treatment.

    Science.gov (United States)

    Dougherty, Paul J; Najibi, Soheil; Silverton, Craig; Vaidya, Rahul

    2009-01-01

    The extremities are the most common anatomic location for gunshot wounds. Because of the prevalence of gunshot injuries, it is important that orthopaedic surgeons are knowledgeable about caring for them. The most common injuries seen with gunshot wounds are those of the soft tissues. Nonsurgical management of patients who have gunshot wounds with minimal soft-tissue disruption has been successfully accomplished in emergency departments for several years; this includes extremity wounds without nerve, intra-articular, or vascular injury. Stable, nonarticular fractures of an extremity have also been successfully treated with either minimal surgical or nonsurgical methods in the emergency department. Indications for surgical treatment include unstable fractures, intra-articular injuries, a significant soft-tissue injury (especially with skin loss), vascular injury, and/or a large or expanding hematoma.

  10. Activation of Bmp2-Smad1 signal and its regulation by coordinated alteration of H3K27 trimethylation in Ras-induced senescence.

    Directory of Open Access Journals (Sweden)

    Atsushi Kaneda

    2011-11-01

    Full Text Available Cellular senescence involves epigenetic alteration, e.g. loss of H3K27me3 in Ink4a-Arf locus. Using mouse embryonic fibroblast (MEF, we here analyzed transcription and epigenetic alteration during Ras-induced senescence on genome-wide scale by chromatin immunoprecipitation (ChIP-sequencing and microarray. Bmp2 was the most activated secreted factor with H3K4me3 gain and H3K27me3 loss, whereas H3K4me3 loss and de novo formation of H3K27me3 occurred inversely in repression of nine genes, including two BMP-SMAD inhibitors Smad6 and Noggin. DNA methylation alteration unlikely occurred. Ras-activated cells senesced with nuclear accumulation of phosphorylated SMAD1/5/8. Senescence was bypassed in Ras-activated cells when Bmp2/Smad1 signal was blocked by Bmp2 knockdown, Smad6 induction, or Noggin induction. Senescence was induced when recombinant BMP2 protein was added to Bmp2-knocked-down Ras-activated cells. Downstream Bmp2-Smad1 target genes were then analyzed genome-wide by ChIP-sequencing using anti-Smad1 antibody in MEF that was exposed to BMP2. Smad1 target sites were enriched nearby transcription start sites of genes, which significantly correlated to upregulation by BMP2 stimulation. While Smad6 was one of Smad1 target genes to be upregulated by BMP2 exposure, Smad6 repression in Ras-activated cells with increased enrichment of Ezh2 and gain of H3K27me3 suggested epigenetic disruption of negative feedback by Polycomb. Among Smad1 target genes that were upregulated in Ras-activated cells without increased repressive mark, Parvb was found to contribute to growth inhibition as Parvb knockdown lead to escape from senescence. It was revealed through genome-wide analyses in this study that Bmp2-Smad1 signal and its regulation by harmonized epigenomic alteration play an important role in Ras-induced senescence.

  11. AEROBIC BACTERIAL ISOLATES FROM INFECTED WOUNDS

    African Journals Online (AJOL)

    boaz

    of wound infection will be helpful in the control of wound infection and selection of empiric antimicrobial therapy as an infection control ... the skin (1). The exposed subcutaneous tissues provides a favourable substratum for a wide variety of microorganisms to contaminate and colonize, and .... Ayton M. Wound care. Wounds ...

  12. Coordinated Regulation and Widespread Cellular Expression of Interferon-Stimulated Genes (ISG) ISG-49, ISG-54, and ISG-56 in the Central Nervous System after Infection with Distinct Viruses▿

    Science.gov (United States)

    Wacher, Christie; Müller, Marcus; Hofer, Markus J.; Getts, Daniel R.; Zabaras, Regina; Ousman, Shalina S.; Terenzi, Fulvia; Sen, Ganes C.; King, Nicholas J. C.; Campbell, Iain L.

    2007-01-01

    The interferon (IFN)-stimulated genes (ISGs) ISG-49, ISG-54, and ISG-56 are highly responsive to viral infection, yet the regulation and function of these genes in vivo are unknown. We examined the simultaneous regulation of these ISGs in the brains of mice during infection with either lymphocytic choriomeningitis virus (LCMV) or West Nile virus (WNV). Expression of the ISG-49 and ISG-56 genes increased significantly during LCMV infection, being widespread and localized predominantly to common as well as distinct neuronal populations. Expression of the ISG-54 gene also increased but to lower levels and with a more restricted distribution. Although expression of the ISG-49, ISG-54, and ISG-56 genes was increased in the brains of LCMV-infected STAT1 and STAT2 knockout (KO) mice, this was blunted, delayed, and restricted to the choroid plexus, meninges, and endothelium. ISG-56 protein was regulated in parallel with the corresponding RNA transcript in the brain during LCMV infection in wild-type and STAT KO mice. Similar changes in ISG-49, ISG-54, and ISG-56 RNA levels and ISG-56 protein levels were observed in the brains of wild-type mice following infection with WNV. Thus, the ISG-49, ISG-54, and ISG-56 genes are coordinately upregulated in the brain during LCMV and WNV infection; this upregulation, in the case of LCMV, was totally (neurons) or partially (non-neurons) dependent on the IFN-signaling molecules STAT1 and STAT2. These findings suggest a dominant role for the ISG-49, ISG-54, and ISG-56 genes in the host response to different viruses in the central nervous system, where, particularly in neurons, these genes may have nonredundant functions. PMID:17079283

  13. Low concentrations of silver nanoparticles have a beneficial effect on wound healing in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Ambrožová, Nikola [Palacký University, Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry (Czech Republic); Zálešák, Bohumil [University Hospital Olomouc, Department of Plastic and Aesthetic Surgery (Czech Republic); Ulrichová, Jitka [Palacký University, Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry (Czech Republic); Čížková, Kateřina [Palacký University, Department of Histology and Embryology, Faculty of Medicine and Dentistry (Czech Republic); Galandáková, Adéla, E-mail: galandakova.a@seznam.cz [Palacký University, Department of Medical Chemistry and Biochemistry, Faculty of Medicine and Dentistry (Czech Republic)

    2017-03-15

    Silver has been used in medical application for its antibacterial, antifungal, and anti-inflammatory effects. Silver nanoparticles (AgNPs) are currently in the spotlight. It was shown that their application can be useful in the management of wounds. Our study was conducted to determine whether AgNPs (average size 10.43 ± 4.74 nm) and ionic silver (Ag-I) could affect the wound healing in the in vitro model of normal human dermal fibroblasts (NHDF). We evaluated their effect on reactive oxygen species (ROS) generation and the expression of key transcription factors that coordinate the cellular response to oxidative stress [nuclear factor (erythroid-derived 2)-like 2 (Nrf2)] and inflammation [nuclear factor-κB (NF-κB)], expression of heme oxygenase-1 (HO-1), and interleukin-6 (IL-6) level. Isolated primary NHDF were scratched, heated (1 h; 42 °C), and cultured with AgNPs (0.25, 2.5, and 25 μg/ml) and Ag-I (0.025, 0.1, and 0.25 μg/ml) for 8 or 24 h. The ROS generation, Nrf2, NF-κB, and HO-1 protein expression and IL-6 protein level were then evaluated by standard methods. Non-cytotoxic concentrations of AgNPs (0.25 and 2.5 μg/ml) did not affect the ROS generation but activated the Nrf2/HO-1 pathway and decreased the NF-κB expression and IL-6 level in the in vitro wound healing model. AgNPs at concentrations of 0.25 and 2.5 μg/ml seem to be suitable for the intended application as a topical agent for wound healing, although the gene silencing technique, chemical inhibitors, and detailed time- and concentration-dependent experiments are needed for a comprehensive study of signaling pathway regulation. Further investigation is also necessary to exclude any possible adverse effects.

  14. Low concentrations of silver nanoparticles have a beneficial effect on wound healing in vitro

    Science.gov (United States)

    Ambrožová, Nikola; Zálešák, Bohumil; Ulrichová, Jitka; Čížková, Kateřina; Galandáková, Adéla

    2017-03-01

    Silver has been used in medical application for its antibacterial, antifungal, and anti-inflammatory effects. Silver nanoparticles (AgNPs) are currently in the spotlight. It was shown that their application can be useful in the management of wounds. Our study was conducted to determine whether AgNPs (average size 10.43 ± 4.74 nm) and ionic silver (Ag-I) could affect the wound healing in the in vitro model of normal human dermal fibroblasts (NHDF). We evaluated their effect on reactive oxygen species (ROS) generation and the expression of key transcription factors that coordinate the cellular response to oxidative stress [nuclear factor (erythroid-derived 2)-like 2 (Nrf2)] and inflammation [nuclear factor-κB (NF-κB)], expression of heme oxygenase-1 (HO-1), and interleukin-6 (IL-6) level. Isolated primary NHDF were scratched, heated (1 h; 42 °C), and cultured with AgNPs (0.25, 2.5, and 25 μg/ml) and Ag-I (0.025, 0.1, and 0.25 μg/ml) for 8 or 24 h. The ROS generation, Nrf2, NF-κB, and HO-1 protein expression and IL-6 protein level were then evaluated by standard methods. Non-cytotoxic concentrations of AgNPs (0.25 and 2.5 μg/ml) did not affect the ROS generation but activated the Nrf2/HO-1 pathway and decreased the NF-κB expression and IL-6 level in the in vitro wound healing model. AgNPs at concentrations of 0.25 and 2.5 μg/ml seem to be suitable for the intended application as a topical agent for wound healing, although the gene silencing technique, chemical inhibitors, and detailed time- and concentration-dependent experiments are needed for a comprehensive study of signaling pathway regulation. Further investigation is also necessary to exclude any possible adverse effects.

  15. Constitutive expression of hypoxia-inducible factor-1 α in keratinocytes during the repair of skin wounds in horses.

    Science.gov (United States)

    Deschene, Karine; Céleste, Christophe; Boerboom, Derek; Theoret, Christine L

    2011-01-01

    As a transient hypoxic state exists within skin wounds in horses and may be important for the healing process, this study sought to identify a molecular hypoxia response occurring in horse limb and body wounds healing by second intention. Hypoxia-inducible factor 1α (HIF1α) protein expression was studied throughout repair by Western blotting and immunofluorescence. Paradoxically, HIF1α was strongly expressed in intact skin and its expression decreased dramatically following wounding (pwounded tissue. HIF1α levels reincreased in parallel with the epithelialization process, and more rapidly in body wounds than in limb wounds (pequine keratinocytes in both intact and wounded skin, and may regulate the expression of CDKN1A in this cell type. © 2011 by the Wound Healing Society.

  16. Negative Pressure Wound Therapy in Maxillofacial Applications

    Directory of Open Access Journals (Sweden)

    Adam J. Mellott

    2016-09-01

    Full Text Available Negative pressure wound therapy has greatly advanced the field of wound healing for nearly two decades, by providing a robust surgical adjunct technique for accelerating wound closure in acute and chronic wounds. However, the application of negative pressure wound therapy in maxillofacial applications has been relatively under utilized as a result of the physical articulations and contours of the head and neck that make it challenging to obtain an airtight seal for different negative pressure wound therapy systems. Adapting negative pressure wound therapies for maxillofacial applications could yield significant enhancement of wound closure in maxillofacial applications. The current review summarizes the basic science underlying negative pressure wound therapy, as well as specific maxillofacial procedures that could benefit from negative pressure wound therapy.

  17. The external microenvironment of healing skin wounds

    DEFF Research Database (Denmark)

    Kruse, Carla R; Nuutila, Kristo; Lee, Cameron Cy

    2015-01-01

    The skin wound microenvironment can be divided into two main components that influence healing: the external wound microenvironment, which is outside the wound surface; and the internal wound microenvironment, underneath the surface, to which the cells within the wound are exposed. Treatment...... and carbon dioxide), pH, and anti-microbial treatment on the wound. These factors are well described in the literature and can be modified with treatment methods available in the clinic. Understanding the roles of these factors in wound pathophysiology is of central importance in wound treatment...... methods that directly alter the features of the external wound microenvironment indirectly affect the internal wound microenvironment due to the exchange between the two compartments. In this review, we focus on the effects of temperature, pressure (positive and negative), hydration, gases (oxygen...

  18. Anti-inflammatory and wound healing activities of calophyllolide isolated from Calophyllum inophyllum Linn.

    Science.gov (United States)

    Nguyen, Van-Linh; Truong, Cong-Tri; Nguyen, Binh Cao Quan; Vo, Thanh-Niem Van; Dao, Trong-Thuc; Nguyen, Van-Dan; Trinh, Dieu-Thuong Thi; Huynh, Hieu Kim; Bui, Chi-Bao

    2017-01-01

    Due to the high-cost and limitations of current wound healing treatments, the search for alternative approaches or drugs, particularly from medicinal plants, is of key importance. In this study, we report anti-inflammatory and wound healing activities of the major calophyllolide (CP) compound isolated from Calophyllum inophyllum Linn. The results showed that CP had no effect on HaCaT cell viability over a range of concentrations. CP reduced fibrosis formation and effectively promoted wound closure in mouse model without causing body weight loss. The underlying molecular mechanisms of wound repair by CP was investigated. CP markedly reduced MPO activity, and increased M2 macrophage skewing, as shown by up-regulation of M2-related gene expression, which is beneficial to the wound healing process. CP treatment prevented a prolonged inflammatory process by down-regulation of the pro-inflammatory cytokines-IL-1β, IL-6, TNF-α, but up-regulation of the anti-inflammatory cytokine, IL-10. This study is the first to indicate a plausible role for CP in accelerating the process of wound healing through anti-inflammatory activity mechanisms, namely, by regulation of inflammatory cytokines, reduction in MPO, and switching of macrophages to an M2 phenotype. These findings may enable the utilization of CP as a potent therapeutic for cutaneous wound healing.

  19. Anti-inflammatory and wound healing activities of calophyllolide isolated from Calophyllum inophyllum Linn.

    Directory of Open Access Journals (Sweden)

    Van-Linh Nguyen

    Full Text Available Due to the high-cost and limitations of current wound healing treatments, the search for alternative approaches or drugs, particularly from medicinal plants, is of key importance. In this study, we report anti-inflammatory and wound healing activities of the major calophyllolide (CP compound isolated from Calophyllum inophyllum Linn. The results showed that CP had no effect on HaCaT cell viability over a range of concentrations. CP reduced fibrosis formation and effectively promoted wound closure in mouse model without causing body weight loss. The underlying molecular mechanisms of wound repair by CP was investigated. CP markedly reduced MPO activity, and increased M2 macrophage skewing, as shown by up-regulation of M2-related gene expression, which is beneficial to the wound healing process. CP treatment prevented a prolonged inflammatory process by down-regulation of the pro-inflammatory cytokines-IL-1β, IL-6, TNF-α, but up-regulation of the anti-inflammatory cytokine, IL-10. This study is the first to indicate a plausible role for CP in accelerating the process of wound healing through anti-inflammatory activity mechanisms, namely, by regulation of inflammatory cytokines, reduction in MPO, and switching of macrophages to an M2 phenotype. These findings may enable the utilization of CP as a potent therapeutic for cutaneous wound healing.

  20. Postoperative washing of sutured wounds

    Directory of Open Access Journals (Sweden)

    Conrad Harrison

    2016-11-01

    Full Text Available A best evidence topic was written according to the structured protocol. The three part question addressed was: [In patients undergoing closure of surgical wounds with sutures] does [keeping the wound dry for the first 48 h after closure] [reduce the incidence of surgical site infections (SSIs]? 4 relevant papers were culled from the literature and appraised. The authors, date, country, population, study type, main outcomes, key results and study weaknesses were tabulated. Current NICE guidelines recommend cleaning surgical wounds with sterile saline only for the first 48 h following skin closure. We found no evidence that washing wounds with tap water during this period increases the incidence of SSIs compared to keeping them dry. Further randomised controlled trials will enable the construction of conclusive systematic reviews and meta-analyses.

  1. 39 CFR 775.7 - Planning and early coordination.

    Science.gov (United States)

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Planning and early coordination. 775.7 Section 775.7 Postal Service UNITED STATES POSTAL SERVICE ENVIRONMENTAL REGULATIONS NATIONAL ENVIRONMENTAL POLICY ACT PROCEDURES § 775.7 Planning and early coordination. Early planning and coordination among...

  2. Quantifying linguistic coordination

    DEFF Research Database (Denmark)

    Fusaroli, Riccardo; Tylén, Kristian

    task (Bahrami et al 2010, Fusaroli et al. 2012) we extend to linguistic coordination dynamical measures of recurrence employed in the analysis of sensorimotor coordination (such as heart-rate (Konvalinka et al 2011), postural sway (Shockley 2005) and eye-movements (Dale, Richardson and Kirkham 2012...... of linguistic coordination and their effects at a fine-degree....

  3. Topically Applied Connective Tissue Growth Factor/CCN2 Improves Diabetic Preclinical Cutaneous Wound Healing: Potential Role for CTGF in Human Diabetic Foot Ulcer Healing

    Directory of Open Access Journals (Sweden)

    F. R. Henshaw

    2015-01-01

    Full Text Available Aims/Hypothesis. Topical application of CTGF/CCN2 to rodent diabetic and control wounds was examined. In parallel research, correlation of CTGF wound fluid levels with healing rate in human diabetic foot ulcers was undertaken. Methods. Full thickness cutaneous wounds in diabetic and nondiabetic control rats were treated topically with 1 μg rhCTGF or vehicle alone, on 2 consecutive days. Wound healing rate was observed on day 14 and wound sites were examined for breaking strength and granulation tissue. In the human study across 32 subjects, serial CTGF regulation was analyzed longitudinally in postdebridement diabetic wound fluid. Results. CTGF treated diabetic wounds had an accelerated closure rate compared with vehicle treated diabetic wounds. Healed skin withstood more strain before breaking in CTGF treated rat wounds. Granulation tissue from CTGF treatment in diabetic wounds showed collagen IV accumulation compared with nondiabetic animals. Wound α-smooth muscle actin was increased in CTGF treated diabetic wounds compared with untreated diabetic wounds, as was macrophage infiltration. Endogenous wound fluid CTGF protein rate of increase in human diabetic foot ulcers correlated positively with foot ulcer healing rate (r=0.406; P<0.001. Conclusions/Interpretation. These data collectively increasingly substantiate a functional role for CTGF in human diabetic foot ulcers.

  4. New trends in healing chronic wounds

    OpenAIRE

    KREJSKOVÁ, Kamila

    2013-01-01

    Basic theoretical bases As a chronic wound is called a secondarily healing wound which despite adequate therapy does not tend to heal for a period of 6-9 weeks. The cause of the chronic wound occurrence and its transformation into an acute wound can be infection, influence of associated diseases, skin top layer microtraumatization or skin necrosis cavity. Among the most frequent types of chronic wounds there are aligned venous ulcerations, arterial rodent ulcers, decubitus ulcers and neuropat...

  5. Wound bed preparation from a clinical perspective

    OpenAIRE

    Halim, A. S.; Khoo, T L; Mat Saad, A. Z.

    2012-01-01

    Wound bed preparation has been performed for over two decades, and the concept is well accepted. The ′TIME′ acronym, consisting of tissue debridement, i nfection or inflammation, moisture balance and edge effect, has assisted clinicians systematically in wound assessment and management. While the focus has usually been concentrated around the wound, the evolving concept of wound bed preparation promotes the treatment of the patient as a whole. This article discusses wound bed preparation and ...

  6. Dressing wounds with potato peel

    Directory of Open Access Journals (Sweden)

    Patange Vidya

    1996-01-01

    Full Text Available The use of boiled potato peel (PP in dressing of various skin conditions was studied. A total of 11 patients were selected, which included resistant wounds of pemphigus, bullous pemphigoid and leg ulcers. An autoclaved PP dressing with a thin layer of antiseptic cream was applied at 25 sites. It was covered with multilayered gauze and the dressing was secured firmly with either a roller bandage or with an adhesive tape. Complete epithelization was seen at 20 sites (80%, near complete epithelization at one site. There was no satisfactory response at three sites and at one site the result could not be evaluated. The mean duration of healing was one week for superficial wounds and three weeks for deep wounds. The PP dressing facilitates the wound and three weeks for deep wounds. The PP dressing facilitates the wound healing process by providing and maintaining a moist environment. The PP dressing is easy to prepare, apply as well as remove. It is a comfortable dressing and is also cost effective.

  7. CT-based ballistic wound path identification and trajectory analysis in anatomic ballistic phantoms.

    Science.gov (United States)

    Folio, Les R; Fischer, Tatjana V; Shogan, Paul J; Frew, Michael I; Kang, Pil S; Bunger, Rolf; Provenzale, James M

    2011-03-01

    To evaluate the accuracy of computed tomography (CT)-based ballistic wound path identification in phantoms by determining the agreement between actual shooting angles and both trajectory angles measured with a picture archiving and communication system (PACS) angle tool and angles calculated from x, y, z coordinates of the entrance and exit points. In this institutional review board-approved model study, two simulated legs were shot by a trained marksman from 50 yards at six clinometer-measured angles with a 0.30-06 rifle and then scanned at multidetector CT. Radiologists measured the wound path angles on paracoronal reformations by using a PACS angle tool. Observers determined the Cartesian coordinates of the entrance and exit points of the wound paths on axial CT images by using detailed instructions. Angles were calculated from these coordinates by using a computer arctangent function. Agreement between the angles was evaluated with Bland-Altman plots. Means, ranges, and standard deviations of the angles also were determined. Radiologists identified all six wound paths on the CT images. The PACS tool-based measured and coordinate-based calculated angles were within 5° of the shooting angles. Results indicated that in larger study populations, one can be 91% confident that future coordinate-based angle calculations will differ from the actual shooting angle by no more than 5° and 95% confident that PACS tool-based angle measurements will differ from the actual shooting angles by no more than 4.5°. One can be 95% confident that future coordinate-based angle calculations will differ from PACS angle measurements by no more than 4.02°. Study results demonstrated the feasibility of consistent wound path identification and the accuracy of trajectory angle determination in models with use of multidetector CT.

  8. Topical oxygen wound therapies for chronic wounds: a review.

    Science.gov (United States)

    Dissemond, J; Kröger, K; Storck, M; Risse, A; Engels, P

    2015-02-01

    Chronic wounds are an increasing problem in our ageing population and can arise in many different ways. Over the past decades it has become evident that sufficient oxygen supply is an essential factor of appropriate wound healing. Sustained oxygen deficit has a detrimental impact on wound healing, especially for patients with chronic wounds. This has been proven for wounds associated with peripheral arterial occlusive disease (PAOD) and diabetic foot ulcers (particularly in combination with PAOD). However, this is still under debate for other primary diseases. In the past few years several different new therapeutic approaches for topical oxygen therapies have been developed to support wound healing. These tend to fall into one of four categories: (1) delivery of pure oxygen either under pressurised or (2) ambient condition, (3) chemical release of oxygen via an enzymatic reaction or (4) increase of oxygen by facilitated diffusion using oxygen binding and releasing molecules. In this review article, the available therapeutic topical oxygen-delivering approaches and their impact on wound healing are presented and critically discussed. A summary of clinical data, daily treatment recommendations and practicability is provided. J. Dissemond received an honorarium for lectures, advisory boards and/or clinical studies from the following companies: 3M, B. Braun, BSN, Coloplast, Convatec, Draco, Hartmann, KCI, Lohmann&Rauscher, Medoderm, Merz, Sastomed, Systagenix, UCB-Pharma, Urgo. K. Kröger received an honorarium for lectures, advisory boards and/or clinical studies from the following companies: Bayer, Sanofi, GSK, Hartmann, Sastomed, UCB-Pharma, Urgo. M. Storck received an honorarium for lectures for the following companies: KCI, Systagenix, and UCB-Pharma. A. Risse received an honorarium for lectures, advisory boards and/or clinical studies from the following companies: Bracco, Coloplast, Draco, Lilly Deutschland, NovoNordisk, Sastomed, Urgo. P. Engels received an

  9. Annona muricata leaves accelerate wound healing in rats via involvement of Hsp70 and antioxidant defence.

    Science.gov (United States)

    Moghadamtousi, Soheil Zorofchian; Rouhollahi, Elham; Hajrezaie, Maryam; Karimian, Hamed; Abdulla, Mahmood Ameen; Kadir, Habsah Abdul

    2015-06-01

    Annona muricata, a member of the Annonaceae family, is commonly known as soursop and graviola. The leaves of this tropical fruit tree are widely used in folk medicine against skin diseases and abscesses, however there is no scientific evidence justifying the use of A. muricata leaves. The aim of the present study is to evaluate the wound healing potential of ethyl acetate extract of A. muricata leaves (EEAM) towards excisional wound models in rats. Sprague Dawley rats (24) were randomly divided into four groups, viz. (A) vehicle control, (B) low dose of EEAM (5% w/w), (C) high dose of EEAM (10% w/w) and (D) positive control with excisional wound created on the neck area. Wounds were topically dressed twice a day for 15 days. On the 15th day, animals were sacrificed and then processed for immunohistochemical and histological evaluations, including Hematoxylin & Eosin and Masson Trichrome stainings. The activity of antioxidants, namely catalase, glutathione peroxidase and superoxide dismutase, and malondialdehyde (MDA) was measured in wound tissue homogenate. Macroscopic and microscopic analysis of wounds demonstrated a significant wound healing activity shown by EEAM at two doses. Treatment of wounds with ointment containing EEAM caused significant surge in antioxidants activities and decrease in the MDA level of wound tissues compared with vehicle control. The immunohistochemical evaluation revealed conspicuous up-regulation of Hsp70 in treated wounds with EEAM, suggesting the anti-inflammatory effect of EEAM. EEAM exhibited a promising wound healing potential towards excisional wound models in rats. Copyright © 2015. Published by Elsevier Ltd.

  10. Wounding induces local resistance but systemic susceptibility to Botrytis cinerea in pepper plants.

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    García, Tania; Gutiérrez, Jorge; Veloso, Javier; Gago-Fuentes, Raquel; Díaz, José

    2015-03-15

    Cotyledon wounding in pepper caused the early generation of hydrogen peroxide both locally (cotyledons) and systemically (upper true leaves). However, 72 h later there is a different wound response between local and systemic organs, as shown by resistance to the pathogenic fungus Botrytis cinerea, that increased locally and decreased systemically. Signaling by ethylene and jasmonic acid was assessed by using two inhibitors: 1-methylcyclopropene (MCP, inhibitor of ethylene receptors) and ibuprofen (inhibitor of jasmonate biosynthesis). MCP did not affect the modulation of resistance levels to Botrytis by wounding, ruling out the involvement of ethylene signaling. Ibuprofen did not inhibit wound-induced resistance at the local level, but inhibited wound-induced systemic susceptibility. Moreover, changes of biochemical and structural defenses in response to wounding were studied. Peroxidase activity and the expression of a peroxidase gene (CAPO1) increased locally as a response to wounding, but no changes were observed systemically. Lignin deposition was induced in wounded cotyledons, but was repressed in systemic leaves of wounded plants, whereas soluble phenolics did not change locally and decreased systemically. The expression of two other genes involved in plant defense (CABPR1 and CASC1) was also differentially regulated locally and systemically, pointing to a generalized increase in plant defenses at the local level and a systemic decrease as a response to wounding. Wound-induced defenses at the local level coincided with resistance to the necrotroph fungus B. cinerea, whereas depleted defenses in systemic leaves of wounded plants correlated to induced susceptibility against this pathogen. It may be that the local response acts as a sink of energy resources to mount a defense against pathogens, whereas in systemic organs the resources for defense are lower. Copyright © 2015 Elsevier GmbH. All rights reserved.

  11. Movement coordination during conversation.

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    Nida Latif

    Full Text Available Behavioral coordination and synchrony contribute to a common biological mechanism that maintains communication, cooperation and bonding within many social species, such as primates and birds. Similarly, human language and social systems may also be attuned to coordination to facilitate communication and the formation of relationships. Gross similarities in movement patterns and convergence in the acoustic properties of speech have already been demonstrated between interacting individuals. In the present studies, we investigated how coordinated movements contribute to observers' perception of affiliation (friends vs. strangers between two conversing individuals. We used novel computational methods to quantify motor coordination and demonstrated that individuals familiar with each other coordinated their movements more frequently. Observers used coordination to judge affiliation between conversing pairs but only when the perceptual stimuli were restricted to head and face regions. These results suggest that observed movement coordination in humans might contribute to perceptual decisions based on availability of information to perceivers.

  12. Lumican binds ALK5 to promote epithelium wound healing.

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    Osamu Yamanaka

    Full Text Available Lumican (Lum, a small leucine-rich proteoglycan (SLRP family member, has multiple matricellular functions both as an extracellular matrix component and as a matrikine regulating cell proliferation, gene expression and wound healing. To date, no cell surface receptor has been identified to mediate the matrikine functions of Lum. This study aimed to identify a perspective receptor that mediates Lum effects on promoting wound healing. Transforming growth factor-β receptor 1 (ALK5 was identified as a potential Lum-interacting protein through in silico molecular docking and molecular dynamics. This finding was verified by biochemical pull-down assays. Moreover, the Lum function on wound healing was abrogated by an ALK5-specific chemical inhibitor as well as by ALK5 shRNAi. Finally, we demonstrated that eukaryote-specific post-translational modifications are not required for the wound healing activity of Lum, as recombinant GST-Lum fusion proteins purified from E. coli and a chemically synthesized LumC13 peptide (the last C-terminal 13 amino acids of Lum have similar effects on wound healing in vitro and in vivo.

  13. Use of Multiple Adjunctive Negative Pressure Wound Therapy Modalities to Manage Diabetic Lower-Extremity Wounds

    OpenAIRE

    Cole, Windy?E.

    2016-01-01

    Objective: Various treatment options exist for wound healing; however, clinical assessment of the patient and the wound environment must be considered before determining an optimal wound treatment plan. Negative pressure wound therapy alone and/or with an instilled topical solution can be effective in adjunctive management of acute and chronic wounds. Hyperbaric oxygen therapy has also been shown to contribute to the wound-healing process. A pilot evaluation using a multistep approach of adju...

  14. Negative Pressure Wound Therapy in the Management of Combat Wounds: A Critical Review

    OpenAIRE

    Maurya, Sanjay; Bhandari, Prem Singh

    2016-01-01

    Significance: Wounds sustained in a combat trauma often result in a composite tissue loss. Combat injuries, due to high energy transfer to tissues, lead to trauma at multiple anatomical sites. An early wound cover is associated with lower rate of infections and a faster wound healing. The concept of negative pressure wound therapy (NPWT) in the management of combat-related wounds has evolved from the civilian trauma and the wounds from nontraumatic etiologies.

  15. The application of the modified surgical wound dressing in wound care after tracheotomy

    OpenAIRE

    Feng Mei; Wu Ying; Zhu Jing; Wu Xiaoling

    2017-01-01

    Introduction: This study was performed to observe the efficacy of a modified surgical wound dressing applied as part of decannulation wound care after tracheotomy. Methods: Eighty-four patients were randomly allocated into a traditional care group, a surgical wound dressing group, and a modified surgical wound dressing group. Each group comprised 28 patients. The following outcomes were observed and analyzed: infection rate, wound closure time, dressing change frequency, cost of wound care...

  16. Hedgehog signaling contributes to basic fibroblast growth factor-regulated fibroblast migration

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    Zhu, Zhong Xin [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Sun, Cong Cong [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Wenzhou People' s Hospital, Wenzhou, Zhejiang (China); Ting Zhu, Yu; Wang, Ying; Wang, Tao; Chi, Li Sha; Cai, Wan Hui [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Zheng, Jia Yong [Wenzhou People' s Hospital, Wenzhou, Zhejiang (China); Zhou, Xuan [Ningbo First Hospital, Ningbo, Zhejiang (China); Cong, Wei Tao [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Li, Xiao Kun, E-mail: proflxk@163.com [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China); Jin, Li Tai, E-mail: jin_litai@126.com [School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang (China)

    2017-06-15

    Fibroblast migration is a central process in skin wound healing, which requires the coordination of several types of growth factors. bFGF, a well-known fibroblast growth factor (FGF), is able to accelerate fibroblast migration; however, the underlying mechanism of bFGF regulation fibroblast migration remains unclear. Through the RNA-seq analysis, we had identified that the hedgehog (Hh) canonical pathway genes including Smoothened (Smo) and Gli1, were regulated by bFGF. Further analysis revealed that activation of the Hh pathway via up-regulation of Smo promoted fibroblast migration, invasion, and skin wound healing, but which significantly reduced by GANT61, a selective antagonist of Gli1/Gli2. Western blot analyses and siRNA transfection assays demonstrated that Smo acted upstream of phosphoinositide 3-kinase (PI3K)-c-Jun N-terminal kinase (JNK)-β-catenin to promote cell migration. Moreover, RNA-seq and qRT-PCR analyses revealed that Hh pathway genes including Smo and Gli1 were under control of β-catenin, suggesting that β-catenin turn feedback activates Hh signaling. Taken together, our analyses identified a new bFGF-regulating mechanism by which Hh signaling regulates human fibroblast migration, and the data presented here opens a new avenue for the wound healing therapy. - Highlights: • bFGF regulates Hedgehog (Hh) signaling in fibroblasts. • The Smo and Gli two master regulators of Hh signaling positively regulate fibroblast migration. • Smo facilitates β-catenin nuclear translocation via activation PI3K/JNK/GSK3β. • β-catenin positively regulates fibroblast cell migration and the expression of Hh signaling genes including Smo and Gli.

  17. Wound dressings: selecting the most appropriate type.

    Science.gov (United States)

    Broussard, Karen C; Powers, Jennifer Gloeckner

    2013-12-01

    Appropriate wound dressing selection is guided by an understanding of wound dressing properties and an ability to match the level of drainage and depth of a wound. Wounds should be assessed for necrosis and infection, which need to be addressed prior to selecting an ideal dressing. Moisture-retentive dressings include films, hydrogels, hydrocolloids, foams, alginates, and hydrofibers and are useful in a variety of clinical settings. Antimicrobial-impregnated dressings can be useful in wounds that are superficially infected or are at higher risk for infection. For refractory wounds that need more growth stimulation, tissue-engineered dressings have become a viable option in the past few decades, especially those that have been approved for burns, venous ulcers, and diabetic ulcers. As wounds heal, the ideal dressing type may change, depending on the amount of exudate and depth of the wound; thus success in wound dressing selection hinges on recognition of the changing healing environment.

  18. Comparison of silver nylon wound dressing and silver sulfadiazine in partial burn wound therapy.

    Science.gov (United States)

    Abedini, Fereydoon; Ahmadi, Abdollah; Yavari, Akram; Hosseini, Vahid; Mousavi, Sarah

    2013-10-01

    The study aims to perform a comparative assessment of two types of burn wound treatment. To do the assessment, patients with partial thickness burn wounds with total body surface area nylon wound dressing or silver sulfadiazine cream. Efficacy of treatment, use of analgesics, number of wound dressing change, wound infection and final hospitalisation cost were evaluated. The study showed silver nylon wound dressing significantly reduced length of hospital stay, analgesic use, wound infection and inflammation compared with silver sulfadiazine. © 2012 The Authors. International Wound Journal © 2012 John Wiley & Sons Ltd and Medicalhelplines.com Inc.

  19. Pediatric tracheotomy wound complications: incidence and significance.

    Science.gov (United States)

    Jaryszak, Eric M; Shah, Rahul K; Amling, June; Peña, Maria T

    2011-04-01

    To determine the incidence and to describe wound complications and associated risk factors of pediatric tracheotomy. Retrospective case series. Freestanding tertiary care academic pediatric hospital. Sixty-five consecutive children undergoing tracheotomy over 15 months. Postoperative wound complications objectively and independently documented by an advanced practice nurse specializing in tracheotomy care. Secondary outcome measures included comorbidities, mortality rates, and wound status after subsequent examinations and management. The mean (SEM) patient age at tracheotomy was 45 (8.7) months (median age, 9.1 months). The most common indication for tracheotomy was pulmonary disease (36.9%), followed by neurologic impairment and laryngeal abnormalities. There were 19 patients (29%) with and 46 patients (71%) without wound complications. There were no significant differences between the 2 groups in age (P = .68) or weight (P = .55); however, infants younger than 12 months had an increased complication rate (39% vs. 17%, P = .04). The type of tracheotomy tube was predictive of postoperative wound complications (P = .02). All patients with wounds received aggressive local wound care. Five of 13 patients had complete resolution of stomal wounds, whereas 8 patients had persistent wound issues. There were 5 non-wound-related mortalities. With attempts to classify tracheotomy wound breakdowns as reportable events, including never events, increasing emphasis is being placed on posttracheotomy care. This study demonstrates that wound breakdown in pediatric tracheotomy patients is common. These complications can be mitigated, although not prevented completely, with aggressive wound surveillance and specialized wound care.

  20. Bioimpedance measurement based evaluation of wound healing.

    Science.gov (United States)

    Kekonen, Atte; Bergelin, Mikael; Eriksson, Jan-Erik; Vaalasti, Annikki; Ylänen, Heimo; Viik, Jari

    2017-06-22

    Our group has developed a bipolar bioimpedance measurement-based method for determining the state of wound healing. The objective of this study was to assess the capability of the method. To assess the performance of the method, we arranged a follow-up study of four acute wounds. The wounds were measured using the method and photographed throughout the healing process. Initially the bioimpedance of the wounds was significantly lower than the impedance of the undamaged skin, used as a baseline. Gradually, as healing progressed, the wound impedance increased and finally reached the impedance of the undamaged skin. The clinical appearance of the wounds examined in this study corresponded well with the parameters derived from the bioimpedance data. Hard-to-heal wounds are a significant and growing socioeconomic burden, especially in the developed countries, due to aging populations and to the increasing prevalence of various lifestyle related diseases. The assessment and the monitoring of chronic wounds are mainly based on visual inspection by medical professionals. The dressings covering the wound must be removed before assessment; this may disturb the wound healing process and significantly increases the work effort of the medical staff. There is a need for an objective and quantitative method for determining the status of a wound without removing the wound dressings. This study provided evidence of the capability of the bioimpedance based method for assessing the wound status. In the future measurements with the method should be extended to concern hard-to-heal wounds.

  1. Outcomes of neuroischemic wounds treated by a multidisciplinary amputation prevention service.

    Science.gov (United States)

    Vartanian, Shant M; Robinson, Kristin D; Ofili, Kene; Eichler, Charles M; Hiramoto, Jade S; Reyzelman, Alex M; Conte, Michael S

    2015-04-01

    lower extremity revascularization procedures performed at our institution. Multidisciplinary limb salvage teams effectively heal wounds and maintain ambulatory status in patients with limb-threatening neuroischemic wounds. Patient specific factors, such as hindfoot or ankle wounds, can adversely influence the outcome. Even with aggressive care, healing can be prolonged and a substantial proportion of patients can be expected to have a recurrence, making subsequent surveillance mandatory. Our data also suggest that a coordinated amputation prevention program may help to minimize hospital readmissions in this high-risk population. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Wound cleansing for pressure ulcers.

    Science.gov (United States)

    Moore, Zena E H; Cowman, Seamus

    2013-03-28

    Pressure ulcers (also called pressure sores, bed sores and decubitus ulcers) are areas of tissue damage that occur in the elderly, malnourished or acutely ill, who cannot reposition themselves. Pressure ulcers impose a significant financial burden on health care systems and negatively affect quality of life. Wound cleansing is considered an important component of pressure ulcer care. This systematic review seeks to answer the following question: what is the effect of wound cleansing solutions and wound cleansing techniques on the rate of healing of pressure ulcers? For this third update, we searched the Cochrane Wounds Group Specialised Register (searched 3 January 2013); The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 12); Ovid MEDLINE (2010 to November Week 3 2012); Ovid MEDLINE (In-Process & Other Non-Indexed Citations December 31, 2012); Ovid EMBASE (2010 to 2012 Week 52); and EBSCO CINAHL (2010 to 21 December 2012). Randomised controlled trials (RCTs) comparing wound cleansing with no wound cleansing, or different wound cleansing solutions, or different cleansing techniques, were eligible for inclusion if they reported an objective measure of pressure ulcer healing. Two review authors extracted data independently and resolved disagreements through discussion. A structured narrative summary of the included studies was conducted. For dichotomous outcomes, risk ratio (RR), plus 95% confidence intervals (CI) were calculated; for continuous outcomes, mean difference (MD), plus 95% CI were calculated. Meta analysis was not conducted because of the small number of diverse RCTs identified. Two review authors independently assessed each included study using the Cochrane Collaboration tool for assessing risk of bias. One additional eligible study was identified from the updated searches, one study was added to the table of excluded studies. A total of three studies (169 participants) met the inclusion criteria for the

  3. Topical silver for infected wounds.

    Science.gov (United States)

    Beam, Joel W

    2009-01-01

    Vermeulen H, van Hattem JM, Storm-Versloot MN, Ubbink DT. Topical silver for treating infected wounds. Cochrane Database Syst Rev. 2007(1);CD005486. What is the clinical evidence base for silver dressings in the management of contaminated and infected acute and chronic wounds? Investigations were identified by Cochrane Wounds Group Specialized Register (2006), CENTRAL (2006), MEDLINE (2002-2006), EMBASE (2002-2006), CINAHL (2002-2006), and digital dissertations (2006) searches. Product manufacturers were contacted to identify additional eligible studies. The search terms included wound infection, surgical wound infection, ulcer, wound healing, and silver. Each study fulfilled the following criteria: (1) The study was a randomized controlled trial of human participants that compared dressings containing silver with any dressings without silver, dressings with other antiseptics, or dressings with different dosages of silver. (2) The participants were aged 18 years and older with contaminated and infected open wounds of any cause. (3) The study had to evaluate the effectiveness of the dressings using an objective measure of healing. No language or publication status restrictions were imposed, and participants could be recruited in any care setting. Studies were excluded if the wounds were ostomies (surgically formed passages). Study quality assessment was conducted independently by 3 authors using the Dutch Institute for Health Care Improvement and Dutch Cochrane Centre protocols. Characteristics of the study, participants, interventions, and outcome measures were extracted by one author and verified by a second using a standard form. The principal outcome measure was healing (time to complete healing, rate of change in wound area and volume, number and proportion of wounds healed within trial period). Secondary measures were adverse events (eg, pain, maceration, erythema), dressing leakage, and wound odor. Based on the unique comparisons in the studies, a meta

  4. Fungating wounds: management and treatment options.

    Science.gov (United States)

    Tandler, Suzanne; Stephen-Haynes, Jackie

    2017-06-22

    This article defines fungating wounds and considers the underlying cause, location and presentation. The clinical challenges presented by fungating wounds are discussed, with reference to evidence-based care delivery. This includes wound assessment, cleansing, debridement and management of malodour, infection, bleeding and exudate. Guidance on the use of wound management dressings is considered in relation to symptom management. The importance of clinical decision-making and educational preparation in the delivery of evidenced-based care for those with fungating wounds is emphasised. A conclusion is made that the clinician can support the patient with a fungating wound by the delivery of evidenced-based care.

  5. Trauma and wound management: gunshot wounds in horses.

    Science.gov (United States)

    Munsterman, Amelia S; Hanson, R Reid

    2014-08-01

    Bullet wounds in horses can cause a wide array of injuries, determined by the type of projectile, the energy of the bullet on entry, and the type of tissue the bullet encounters. Treatment includes identification of all structures involved, debridement of the permanent cavity, and establishing adequate drainage. Bullet wounds should be treated as contaminated, and broad-spectrum antibiotics, including those with an anaerobic spectrum, are indicated. Although musculoskeletal injuries resulting from gunshots are most common in horses, they carry a good prognosis for survival and return to function. Published by Elsevier Inc.

  6. Hyaluronan and RHAMM in Wound Repair and the “Cancerization” of Stromal Tissues

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    Cornelia Tolg

    2014-01-01

    Full Text Available Tumors and wounds share many similarities including loss of tissue architecture, cell polarity and cell differentiation, aberrant extracellular matrix (ECM remodeling (Ballard et al., 2006 increased inflammation, angiogenesis, and elevated cell migration and proliferation. Whereas these changes are transient in repairing wounds, tumors do not regain tissue architecture but rather their continued progression is fueled in part by loss of normal tissue structure. As a result tumors are often described as wounds that do not heal. The ECM component hyaluronan (HA and its receptor RHAMM have both been implicated in wound repair and tumor progression. This review highlights the similarities and differences in their roles during these processes and proposes that RHAMM-regulated wound repair functions may contribute to “cancerization” of the tumor microenvironment.

  7. Differential activation of sporamin expression in response to abiotic mechanical wounding and biotic herbivore attack in the sweet potato

    Science.gov (United States)

    2014-01-01

    Background Plants respond differently to mechanical wounding and herbivore attack, using distinct pathways for defense. The versatile sweet potato sporamin possesses multiple biological functions in response to stress. However, the regulation of sporamin gene expression that is activated upon mechanical damage or herbivore attack has not been well studied. Results Biochemical analysis revealed that different patterns of Reactive oxygen species (ROS) and antioxidant mechanism exist between mechanical wounding (MW) and herbivore attack (HA) in the sweet potato leaf. Using LC-ESI-MS (Liquid chromatography electrospray ionization mass spectrometry analysis), only the endogenous JA (jasmonic acid) level was found to increase dramatically after MW in a time-dependent manner, whereas both endogenous JA and SA (salicylic acid) increase in parallel after HA. Through yeast one-hybrid screening, two transcription factors IbNAC1 (no apical meristem (NAM), Arabidopsis transcription activation factor (ATAF), and cup-shaped cotyledon (CUC)) and IbWRKY1 were isolated, which interact with the sporamin promoter fragment of SWRE (sporamin wounding-responsive element) regulatory sequences. Exogenous application of MeJA (methyl jasmonate), SA and DIECA (diethyldithiocarbamic acid, JAs biosynthesis inhibitor) on sweet potato leaves was employed, and the results revealed that IbNAC1 mediated the expression of sporamin through a JA-dependent signaling pathway upon MW, whereas both IbNAC1 and IbWRKY1 coordinately regulated sporamin expression through JA- and SA-dependent pathways upon HA. Transcriptome analysis identified MYC2/4 and JAZ2/TIFY10A (jasmonate ZIM/tify-domain), the repressor and activator of JA and SA signaling among others, as the genes that play an intermediate role in the JA and SA pathways, and these results were further validated by qRT-PCR (quantitative real-time polymerase chain reaction). Conclusion This work has improved our understanding of the differential

  8. Wounds written in the genes

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    Adele Nunziante Cesàro

    2016-08-01

    Full Text Available In a psychodynamic framework, the authors reflect upon the transmission of the BRCA1/2 genes’ mutation. This mutation exposes carrier women to the risk of developing, during their lives, a form of breast and/or ovarian cancer. This illness has already affected different women of their family causing wounds inscribed in soma and in psyche. These wounds are significant in woman’s decision making of prevention strategies. It is very hard to care wounds inscribed in one’s own history that became a threat for femininity. The authors use women’s narration as material to be analysed in order to highlight the meanings linked to the mutation between identity, group and generational dimensions.

  9. [Application of modern wound dressings in the treatment of chronic wounds].

    Science.gov (United States)

    Triller, Ciril; Huljev, Dubravko; Smrke, Dragica Maja

    2012-10-01

    Chronic and acute infected wounds can pose a major clinical problem because of associated complications and slow healing. In addition to classic preparations for wound treatment, an array of modern dressings for chronic wound care are currently available on the market. These dressings are intended for the wounds due to intralesional physiological, pathophysiological and pathological causes and which failed to heal as expected upon the use of standard procedures. Classic materials such as gauze and bandage are now considered obsolete and of just historical relevance because modern materials employed in wound treatment, such as moisture, warmth and appropriate pH are known to ensure optimal conditions for wound healing. Modern wound dressings absorb wound discharge, reduce bacterial contamination, while protecting wound surrounding from secondary infection and preventing transfer of infection from the surrounding area onto the wound surface. The use of modern wound dressings is only justified when the cause of wound development has been established or chronic wound due to the underlying disease has been diagnosed. Wound dressing is chosen according to wound characteristics and by experience. We believe that the main advantages of modern wound dressings versus classic materials include more efficient wound cleaning, simpler placement of the dressing, reduced pain to touch, decreased sticking to the wound surface, and increased capacity of absorbing wound exudate. Modern wound dressings accelerate the formation of granulation tissue, reduce the length of possible hospital stay and facilitate personnel work. Thus, the overall cost of treatment is reduced, although the price of modern wound dressings is higher than that of classic materials. All types of modern wound dressings, their characteristics and indications for use are described.

  10. Recent advances in topical wound care

    Directory of Open Access Journals (Sweden)

    Sujata Sarabahi

    2012-01-01

    Full Text Available There are a wide variety of dressing techniques and materials available for management of both acute wounds and chronic non-healing wounds. The primary objective in both the cases is to achieve a healed closed wound. However, in a chronic wound the dressing may be required for preparing the wound bed for further operative procedures such as skin grafting. An ideal dressing material should not only accelerate wound healing but also reduce loss of protein, electrolytes and fluid from the wound, and help to minimize pain and infection. The present dictum is to promote the concept of moist wound healing. This is in sharp contrast to the earlier practice of exposure method of wound management wherein the wound was allowed to dry. It can be quite a challenge for any physician to choose an appropriate dressing material when faced with a wound. Since wound care is undergoing a constant change and new products are being introduced into the market frequently, one needs to keep abreast of their effect on wound healing. This article emphasizes on the importance of assessment of the wound bed, the amount of drainage, depth of damage, presence of infection and location of wound. These characteristics will help any clinician decide on which product to use and where,in order to get optimal wound healing. However, there are no ′magical dressings′. Dressings are one important aspect that promotes wound healing apart from treating the underlying cause and other supportive measures like nutrition and systemic antibiotics need to be given equal attention.

  11. Wound healing in animal models: review article

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    Fariba Jaffary

    2017-10-01

    Full Text Available Wound healing and reduction of its recovery time is one of the most important issues in medicine. Wound is defined as disruption of anatomy and function of normal skin. This injury could be the result of physical elements such as  surgical incision, hit or pressure cut of the skin and gunshot wound. Chemical or caustic burn is another category of wound causes that can be induced by acid or base contact irritation. Healing is a process of cellular and extracellular matrix interactions that occur in the damaged tissue. Wound healing consists of several stages including hemostasis, inflammatory phase, proliferative phase and new tissue formation which reconstructs by new collagen formation. Wounds are divided into acute and chronic types based on their healing time. Acute wounds have sudden onset and in normal individuals usually have healing process of less than 4 weeks without any residual side effects. In contrast, chronic wounds have gradual onset. Their inflammatory phase is prolonged and the healing process is stopped due to some background factors like diabetes, ischemia or local pressure. If the healing process lasts more than 4 weeks it will be classified as chronic wound. Despite major advances in the treatment of wounds, still finding effective modalities for healing wounds in the shortest possible time with the fewest side effects is a current challenge. In this review different phases of wound healing and clinical types of wound such as venous leg ulcer, diabetic foot ulcer and pressure ulcer are discussed. Also acute wound models (i.e burn wounds or incisional wound and chronic wound models (such as venous leg ulcers, diabetic foot ulcer, pressure ulcers or bedsore in laboratory animals are presented. This summary can be considered as a preliminary step to facilitate designing of more targeted and applied research in this area.

  12. Expression and function of connexin 43 in human gingival wound healing and fibroblasts.

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    Rana Tarzemany

    Full Text Available Connexins (C×s are a family of transmembrane proteins that form hemichannels and gap junctions (GJs on the cell membranes, and transfer small signaling molecules between the cytoplasm and extracellular space and between connecting cells, respectively. Among C×s, suppressing C×43 expression or function promotes skin wound closure and granulation tissue formation, and may alleviate scarring, but the mechanisms are not well understood. Oral mucosal gingiva is characterized by faster wound closure and scarless wound healing outcome as compared to skin wounds. Therefore, we hypothesized that C×43 function is down regulated during human gingival wound healing, which in fibroblasts promotes expression of genes conducive for fast and scarless wound healing. Cultured gingival fibroblasts expressed C×43 as their major connexin. Immunostaining of unwounded human gingiva showed that C×43 was abundantly present in the epithelium, and in connective tissue formed large C×43 plaques in fibroblasts. At the early stages of wound healing, C×43 was strongly down regulated in wound epithelial cells and fibroblasts, returning to the level of normal tissue by day 60 post-wounding. Blocking of C×43 function by C×43 mimetic peptide Gap27 suppressed GJ-mediated dye transfer, promoted migration, and caused significant changes in the expression of wound healing-associated genes in gingival fibroblasts. In particular, out of 54 genes analyzed, several MMPs and TGF-β1, involved in regulation of inflammation and extracellular matrix (ECM turnover, and VEGF-A, involved in angiogenesis, were significantly upregulated while pro-fibrotic ECM molecules, including Collagen type I, and cell contractility-related molecules were significantly down regulated. These responses involved MAPK, GSK3α/β and TGF-β signaling pathways, and AP1 and SP1 transcription factors. Thus, suppressed function of C×43 in fibroblasts promotes their migration, and regulates expression of

  13. Small Cytoskeleton-Associated Molecule, Fibroblast Growth Factor Receptor 1 Oncogene Partner 2/Wound Inducible Transcript-3.0 (FGFR1OP2/wit3.0), Facilitates Fibroblast-Driven Wound Closure

    OpenAIRE

    Lin, Audrey; Hokugo, Akishige; Choi, Jae; Nishimura, Ichiro

    2010-01-01

    Wounds created in the oral cavity heal rapidly and leave minimal scarring. We have examined a role of a previously isolated cDNA from oral wounds encoding wound inducible transcript-3.0 (wit3.0), also known as fibroblast growth factor receptor 1 oncogene partner 2 (FGFR1OP2). FGFR1OP2/wit3.0 was highly expressed in oral wound fibroblasts without noticeable up-regulation of α-smooth muscle actin. In silico analyses, denaturing and nondenaturing gel Western blot, and immunocytology together dem...

  14. Gene expression profiling of cutaneous wound healing

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    Wang Ena

    2007-02-01

    Full Text Available Abstract Background Although the sequence of events leading to wound repair has been described at the cellular and, to a limited extent, at the protein level this process has yet to be fully elucidated. Genome wide transcriptional analysis tools promise to further define the global picture of this complex progression of events. Study Design This study was part of a placebo-controlled double-blind clinical trial in which basal cell carcinomas were treated topically with an immunomodifier – toll-like receptor 7 agonist: imiquimod. The fourteen patients with basal cell carcinoma in the placebo arm of the trial received placebo treatment consisting solely of vehicle cream. A skin punch biopsy was obtained immediately before treatment and at the end of the placebo treatment (after 2, 4 or 8 days. 17.5K cDNA microarrays were utilized to profile the biopsy material. Results Four gene signatures whose expression changed relative to baseline (before wound induction by the pre-treatment biopsy were identified. The largest group was comprised predominantly of inflammatory genes whose expression was increased throughout the study. Two additional signatures were observed which included preferentially pro-inflammatory genes in the early post-treatment biopsies (2 days after pre-treatment biopsies and repair and angiogenesis genes in the later (4 to 8 days biopsies. The fourth and smallest set of genes was down-regulated throughout the study. Early in wound healing the expression of markers of both M1 and M2 macrophages were increased, but later M2 markers predominated. Conclusion The initial response to a cutaneous wound induces powerful transcriptional activation of pro-inflammatory stimuli which may alert the host defense. Subsequently and in the absence of infection, inflammation subsides and it is replaced by angiogenesis and remodeling. Understanding this transition which may be driven by a change from a mixed macrophage population to predominately M2

  15. A prospective pilot study to evaluate wound outcomes and levels of serum C-reactive protein and interleukin-6 in the wound fluid of patients with trauma-related chronic wounds.

    Science.gov (United States)

    Liu, Tao; Yang, Fan; Li, Zhanfei; Yi, Chengla; Bai, Xiangjun

    2014-06-01

    If surgical closure of chronic wounds is an option, choosing an appropriate time to definitely close these wounds remains a challenge. Although the underlying mechanisms of nonhealing are not completely understood, serum C-reactive protein (CRP) and interleukin-6 (IL-6) in wound fluid have been found to be markers of the systemic and local inflammation state of chronic wounds. The purpose of this prospective, descriptive pilot study was to evaluate the effect of debridement, systemic antibiotics, and negative pressure wound therapy (NPWT) on the outcomes of trauma-related chronic wounds and changes in local inflammation responses, measured using CRP and IL-6 levels as indicators of cytokine regulation. Between June 2012 and May 2013, 20 consecutive patients (14 men, six women, mean age 40 [range 17-56] years) with various trauma-related, nonhealing chronic wounds were enrolled in the study after failing to heal for an average of 8.5 (range 6-16) weeks using a protocol of regular debridement and gauze dressings. Before the start of the study, wounds were cultured, and laboratory values for white blood cell count (WBC), neutrophils, and levels of serum CRP and IL-6 in the wound fluid obtained. Wounds were surgically debrided and NPWT (continuous at 125 mm Hg) applied. All patients were prescribed systemic antibiotics, and mean time interval between NPWT dressing changes was 5 (range 3-7) days. During an average mean NPWT treatment time of 13 (range 5-20) days, CRP and IL-6 concentrations decreased from 66.4 mg/L to 10.4 mg/L and 44.1 pg/mL to 8.6 pg/mL, respectively (P wounds were successfully closed using various surgical procedures. In this study, clinical wound improvement and a significant decrease in wound fluid CRP and IL-6 levels were observed. Studies with a larger sample size and a more robust study design may help elucidate the relationship between inflammatory molecules, infection, and healing outcomes.

  16. The transcriptional activation program of human neutrophils in skin lesions supports their important role in wound healing

    DEFF Research Database (Denmark)

    Theilgaard-Monch, K.; Knudsen, Steen; Follin, P.

    2004-01-01

    receptors involved in inflammatory responses. These findings indicate a change of responsiveness to chemotactic and immunoregulatory mediators once PMNs have migrated to skin lesions and have been activated. Other effects of the up-regulated cytokines/chemokines/enzymes were critical for wound healing......To investigate the cellular fate and function of polymorphonuclear neutrophilic granulocytes (PMNs) attracted to skin wounds, we used a human skin-wounding model and microarray technology to define differentially expressed genes in PMNs from peripheral blood, and PMNs that had transmigrated to skin...... and function, and promotes wound healing....

  17. The Role of Poly N Acetyl Glucosamine Nanofibers in Cutaneous Wound Healing

    Science.gov (United States)

    Buff-Lindner, Amanda Haley

    Treatment of cutaneous wounds with poly-N-acetyl-glucosamine nanofibers (pGlcNAc), a novel polysaccharide material derived from a marine diatom, results in increases in wound closure, antibacterial activities and innate immune responses. Treatment with nanofibers results in increased defensin, small antimicrobial peptides, expression both in vitro and in vivo. Induction of defensin expression results in bacterial clearance in a cutaneous wound model. Our data show that Akt1 plays a central role in the regulation of these activities. Interestingly, pGlcNAc treatment of cutaneous wounds in mice results in decreased scar sizes. Additionally, treatment of cutaneous wounds with pGlcNAc results in increased elasticity and a rescue of tensile strength. Masson Trichrome staining suggests that pGlcNAc treated wounds exhibit decreased collagen content as well as increased collagen alignment with collagen fibers oriented similarly to unwounded tissue. Utilizing a fibrin gel assay to analyze the effect of pGlcNAc nanofiber treatment on fibroblast alignment in vitro, pGlcNAc stimulation of embedded fibroblasts results in fibroblasts alignment as compared to untreated controls, by a process that is Akt1 dependent. Our data show that in Akt1 null animals pGlcNAc treatment does not increase tensile strength or elasticity. Taken together, our findings suggest that pGlcNAc nanofibers stimulate an Akt1 dependent pathway that results in wound closure, the proper alignment of fibroblasts, decreased scarring, and increased tensile strength during cutaneous wound healing.

  18. Valproic acid induces cutaneous wound healing in vivo and enhances keratinocyte motility.

    Directory of Open Access Journals (Sweden)

    Soung-Hoon Lee

    Full Text Available BACKGROUND: Cutaneous wound healing is a complex process involving several signaling pathways such as the Wnt and extracellular signal-regulated kinase (ERK signaling pathways. Valproic acid (VPA is a commonly used antiepileptic drug that acts on these signaling pathways; however, the effect of VPA on cutaneous wound healing is unknown. METHODS AND FINDINGS: We created full-thickness wounds on the backs of C3H mice and then applied VPA. After 7 d, we observed marked healing and reduced wound size in VPA-treated mice. In the neo-epidermis of the wounds, β-catenin and markers for keratinocyte terminal differentiation were increased after VPA treatment. In addition, α-smooth muscle actin (α-SMA, collagen I and collagen III in the wounds were significantly increased. VPA induced proliferation and suppressed apoptosis of cells in the wounds, as determined by Ki67 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL staining analyses, respectively. In vitro, VPA enhanced the motility of HaCaT keratinocytes by activating Wnt/β-catenin, ERK and phosphatidylinositol 3-kinase (PI3-kinase/Akt signaling pathways. CONCLUSIONS: VPA enhances cutaneous wound healing in a murine model and induces migration of HaCaT keratinocytes.

  19. Therapeutic Effects of Acupuncture through Enhancement of Functional Angiogenesis and Granulogenesis in Rat Wound Healing

    Directory of Open Access Journals (Sweden)

    Sang In Park

    2012-01-01

    Full Text Available Acupuncture regulates inflammation process and growth factors by increasing blood circulation in affected areas. In this study, we examined whether acupuncture has an effect on wound healing in injured rat. Rats were assigned randomly into two groups: control group and acupuncture group. Acupuncture treatment was carried out at 8 sites around the wounded area. We analyzed the wound area, inflammatory cytokines, proliferation of resident cells, and angiogenesis and induction of extracelluar matrix remodeling. At 7 days after-wounding the wound size in acupuncture-treat group was decreased more significantly compared to control group. In addition, the protein levels of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α and interleukin-1β (IL-1β were significantly decreased compared to the control at 2 and 7 days post-wounding. Also, we analyzed newly generated cells by performing immunostaining for PCNA and using several phenotype markers such as CD-31, α-SMA, and collagen type I. In acupuncture-treated group, PCNA-positive cell was increased and PCNA labeled CD-31-positive vessels, α-SMA- and collagen type I-positive fibroblastic cells, were increased compared to the control group at 7 days post-wounding. These results suggest that acupuncture may improve wound healing through decreasing pro-inflammatory response, increasing cell proliferation and angiogenesis, and inducing extracellular matrix remodeling.

  20. Emergency Wound Care After a Natural Disaster

    Science.gov (United States)

    ... Disease Transmission in Pet Shelters Protect Your Pets Emergency Wound Care After a Natural Disaster Language: English ( ... Tweet Share Compartir Print-and-Go Fact Sheet Emergency Wound Care After a Natural Disaster [NOTE: Health ...

  1. Novel wound sealants: biomaterials and applications.

    Science.gov (United States)

    Peng, Henry T; Shek, Pang N

    2010-09-01

    Wound sealants provide an excellent alternative for closing surgical and non-surgical wounds, as well as stopping external bleeding for prehospital trauma injuries. Numerous biomaterials have been investigated to address specific requirements for their use as suitable wound sealants. This article focuses on the development of new wound sealant biomaterials and recent advances in the surgical applications of wound sealants. In the past 5 years, many new sealant materials had been reported, including keratin, mussel-adhesive proteins, dendrimers and in situ-forming hydrogels. Fibrin sealants remain the most clinically studied for a variety of surgical procedures, while clinical experience with wound sealants for orthopedic surgery is limited. Both liquid and solid wound sealants have been developed and found effective by possessing strong adhesive properties. Biocompatible and biodegradable wound sealants hold much promise in eventually replacing sutures in most surgical procedures.

  2. Molecular cloning and characterization of a tomato cDNA encoding a systemically wound-inducible bZIP DNA-binding protein

    Science.gov (United States)

    Stankovic, B.; Vian, A.; Henry-Vian, C.; Davies, E.

    2000-01-01

    Localized wounding of one leaf in intact tomato (Lycopersicon esculentum Mill.) plants triggers rapid systemic transcriptional responses that might be involved in defense. To better understand the mechanism(s) of intercellular signal transmission in wounded tomatoes, and to identify the array of genes systemically up-regulated by wounding, a subtractive cDNA library for wounded tomato leaves was constructed. A novel cDNA clone (designated LebZIP1) encoding a DNA-binding protein was isolated and identified. This clone appears to be encoded by a single gene, and belongs to the family of basic leucine zipper domain (bZIP) transcription factors shown to be up-regulated by cold and dark treatments. Analysis of the mRNA levels suggests that the transcript for LebZIP1 is both organ-specific and up-regulated by wounding. In wounded wild-type tomatoes, the LebZIP1 mRNA levels in distant tissue were maximally up-regulated within only 5 min following localized wounding. Exogenous abscisic acid (ABA) prevented the rapid wound-induced increase in LebZIP1 mRNA levels, while the basal levels of LebZIP1 transcripts were higher in the ABA mutants notabilis (not), sitiens (sit), and flacca (flc), and wound-induced increases were greater in the ABA-deficient mutants. Together, these results suggest that ABA acts to curtail the wound-induced synthesis of LebZIP1 mRNA.

  3. Wound healing and all-cause mortality in 958 wound patients treated in home care.

    Science.gov (United States)

    Zarchi, Kian; Martinussen, Torben; Jemec, Gregor B E

    2015-09-01

    Skin wounds are associated with significant morbidity and mortality. Data are, however, not readily available for benchmarking, to allow prognostic evaluation, and to suggest when involvement of wound-healing experts is indicated. We, therefore, conducted an observational cohort study to investigate wound healing and all-cause mortality associated with different types of skin wounds. Consecutive skin wound patients who received wound care by home-care nurses from January 2010 to December 2011 in a district in Eastern Denmark were included in this study. Patients were followed until wound healing, death, or the end of follow-up on December 2012. In total, 958 consecutive patients received wound care by home-care nurses, corresponding to a 1-year prevalence of 1.2% of the total population in the district. During the study, wound healing was achieved in 511 (53.3%), whereas 90 (9.4%) died. During the first 3 weeks of therapy, healing was most likely to occur in surgical wounds (surgical vs. other wounds: adjusted hazard ratio [AHR] 2.21, 95% confidence interval 1.50-3.23), while from 3 weeks to 3 months of therapy, cancer wounds, and pressure ulcers were least likely to heal (cancer vs. other wounds: AHR 0.12, 0.03-0.50; pressure vs. other wounds: AHR 0.44, 0.27-0.74). Cancer wounds and pressure ulcers were further associated with a three times increased probability of mortality compared with other wounds (cancer vs. other wounds: AHR 3.19, 1.35-7.50; pressure vs. other wounds: AHR 2.91, 1.56-5.42). In summary, the wound type was found to be a significant predictor of healing and mortality with cancer wounds and pressure ulcers being associated with poor prognosis. © 2015 by the Wound Healing Society.

  4. Coordinate measuring machines

    DEFF Research Database (Denmark)

    De Chiffre, Leonardo

    This document is used in connection with three exercises of 2 hours duration as a part of the course GEOMETRICAL METROLOGY AND MACHINE TESTING. The exercises concern three aspects of coordinate measuring: 1) Measuring and verification of tolerances on coordinate measuring machines, 2) Traceabilit...

  5. Negative Pressure Wound Therapy in the Management of Combat Wounds: A Critical Review

    Science.gov (United States)

    Maurya, Sanjay; Bhandari, Prem Singh

    2016-01-01

    Significance: Wounds sustained in a combat trauma often result in a composite tissue loss. Combat injuries, due to high energy transfer to tissues, lead to trauma at multiple anatomical sites. An early wound cover is associated with lower rate of infections and a faster wound healing. The concept of negative pressure wound therapy (NPWT) in the management of combat-related wounds has evolved from the civilian trauma and the wounds from nontraumatic etiologies. Recent Advances: Encouraged by the results of NPWT in noncombat-related wounds, the military surgeons during Operation Iraqi Freedom and Operation Enduring Freedom used this novel method in a large percentage of combat wounds, with gratifying results. The mechanism of NPWT in wound healing is multifactorial and often complex reconstructive procedure can be avoided in a combat trauma setting. Critical Issues: Wounds sustained in military trauma are heavily contaminated with dirt, patient clothing, and frequently associated with extensive soft tissue loss and osseous destruction. Delay in evacuation during an ongoing conflict carries the risk of systemic infection. Early debridement is indicated followed by delayed closure of wounds. NPWT helps to provide temporary wound cover during the interim period of debridement and wound closure. Future Directions: Future area of research in combat wounds is related to abdominal trauma with loss of abdominal wall. The concept of negative pressure incisional management system in patients with a high risk of wound breakdown following surgery is under review, and may be of relevance in combat wounds. PMID:27679749

  6. Predicting complex acute wound healing in patients from a wound expertise centre registry : a prognostic study

    NARCIS (Netherlands)

    Ubbink, Dirk T; Lindeboom, Robert; Eskes, Anne M; Brull, Huub; Legemate, Dink A; Vermeulen, Hester

    2015-01-01

    It is important for caregivers and patients to know which wounds are at risk of prolonged wound healing to enable timely communication and treatment. Available prognostic models predict wound healing in chronic ulcers, but not in acute wounds, that is, originating after trauma or surgery. We

  7. Predicting complex acute wound healing in patients from a wound expertise centre registry: a prognostic study

    NARCIS (Netherlands)

    Ubbink, Dirk T.; Lindeboom, Robert; Eskes, Anne M.; Brull, Huub; Legemate, Dink A.; Vermeulen, Hester

    2015-01-01

    It is important for caregivers and patients to know which wounds are at risk of prolonged wound healing to enable timely communication and treatment. Available prognostic models predict wound healing in chronic ulcers, but not in acute wounds, that is, originating after trauma or surgery. We

  8. Coordination failure caused by sunspots

    DEFF Research Database (Denmark)

    Beugnot, Julie; Gürgüç, Zeynep; Øvlisen, Frederik Roose

    2012-01-01

    In a coordination game with Pareto-ranked equilibria, we study whether a sunspot can lead to either coordination on an inferior equilibrium (mis-coordination) or to out-of equilibrium behavior (dis-coordination). While much of the literature searches for mechanisms to attain coordination on the e......In a coordination game with Pareto-ranked equilibria, we study whether a sunspot can lead to either coordination on an inferior equilibrium (mis-coordination) or to out-of equilibrium behavior (dis-coordination). While much of the literature searches for mechanisms to attain coordination...

  9. The mechanical fingerprint of murine excisional wounds.

    Science.gov (United States)

    Pensalfini, Marco; Haertel, Eric; Hopf, Raoul; Wietecha, Mateusz; Werner, Sabine; Mazza, Edoardo

    2018-01-01

    A multiscale mechanics approach to the characterization of murine excisional wounds subjected to uniaxial tensile loading is presented. Local strain analysis at a physiological level of tension uncovers the presence of two distinct regions within the wound: i) a very compliant peripheral cushion and ii) a core area undergoing modest deformation. Microstructural visualizations of stretched wound specimens show negligible engagement of the collagen located in the center of a 7-day old wound; fibers remain coiled despite the applied tension, confirming the existence of a mechanically isolated wound core. The compliant cushion located at the wound periphery appears to protect the newly-formed tissue from excessive deformation during the phase of new tissue formation. The early remodeling phase (day 14) is characterized by a restored mechanical connection between far field and wound center. The latter remains less deformable, a characteristic possibly required for cell activities during tissue remodeling. The distribution of fibrillary collagens at these two time points corresponds well to the identified heterogeneity of mechanical properties of the wound region. This novel approach provides new insight into the mechanical properties of wounded skin and will be applicable to the analysis of compound-treated wounds or wounds in genetically modified tissue. Biophysical characterization of healing wounds is crucial to assess the recovery of the skin barrier function and the associated mechanobiological processes. For the first time, we performed highly resolved local deformation analysis to identify mechanical characteristics of the wound and its periphery. Our results reveal the presence of a compliant cushion surrounding a stiffer wound core; we refer to this heterogeneous mechanical behavior as "mechanical fingerprint" of the wound. The mechanical response is shown to progress towards that of the intact skin as healing takes place. Histology and multiphoton microscopy

  10. Metal-coordination: using more of nature's tricks to assemble new soft materials

    Science.gov (United States)

    Holten-Andersen, Niels

    2014-03-01

    Growing evidence supports a critical role of metal-coordination in soft biological material properties such as self-healing, underwater adhesion and autonomous wound plugging. Using bio-inspired metal-coordinating polymers, initial efforts to mimic these properties have shown promise. In addition, with polymer network mechanics dictated by coordinate crosslink dynamics material properties can be easily tuned from visco-elastic fluids to elastic solids. Given their exploitation in desirable material applications in nature, metal-coordinate crosslinking provides an opportunity to advance synthetic polymer materials design. Early lessons from this pursuit are presented.

  11. Bio-Inspired Metal-Coordination Dynamics: A Unique Tool for Engineering Soft Matter Mechanics

    Science.gov (United States)

    Holten-Andersen, Niels

    Growing evidence supports a critical role of metal-coordination in soft biological material properties such as self-healing, underwater adhesion and autonomous wound plugging. Using bio-inspired metal-binding polymers, initial efforts to mimic these properties with metal-coordination crosslinked polymer materials have shown promise. In addition, with polymer network mechanics strongly coupled to coordinate crosslink dynamics material properties can be easily tuned from visco-elastic fluids to solids. Given their exploitation in desirable material applications in Nature, bio-inspired metal-coordinate complex crosslinking provides an opportunity to further advance synthetic polymer materials design. Early lessons from this pursuit are presented.

  12. β-glucan enriched bath directly stimulates the wound healing process in common carp (Cyprinus carpio L.)

    DEFF Research Database (Denmark)

    Przybylska, Dominika Alicja; Schmidt, Jacob; Jiménez, Natalia Ivonne Vera

    2013-01-01

    activated in all wounds regardless of treatment. Expression of all three interleukins was highly up regulated in control wounded muscle already at day 1 post-wounding and decreased at subsequent time-points. The reverse was the case with control wounded skin, where expression increased from day 1 through......Wound healing is a complex and well-organized process in which physiological factors and immune mechanisms are involved. A number of different immune modulators have been found to enhance the non-specific defence system in vertebrates, among which β-glucans are the most powerful and extensively...... investigated. The aim of the present study was to investigate the biological impact of two different commercially available β glucan containing products on the wound healing process in carp. Throughout a two week experiment fish were kept either untreated (control), or in water supplemented with the two...

  13. Proline Precursors and Collagen Synthesis: Biochemical Challenges of Nutrient Supplementation and Wound Healing.

    Science.gov (United States)

    Albaugh, Vance L; Mukherjee, Kaushik; Barbul, Adrian

    2017-11-01

    Wound healing is a complex process marked by highly coordinated immune fluxes into an area of tissue injury; these are required for re-establishment of normal tissue integrity. Along with this cascade of cellular players, wound healing also requires coordinated flux through a number of biochemical pathways, leading to synthesis of collagen and recycling or removal of damaged tissues. The availability of nutrients, especially amino acids, is critical for wound healing, and enteral supplementation has been intensely studied as a potential mechanism to augment wound healing-either by increasing tensile strength, decreasing healing time, or both. From a practical standpoint, although enteral nutrient supplementation may seem like a reasonable strategy to augment healing, a number of biochemical and physiologic barriers exist that limit this strategy. In this critical review, the physiology of enteral amino acid metabolism and supplementation and challenges therein are discussed in the context of splanchnic physiology and biochemistry. Additionally, a review of studies examining various methods of amino acid supplementation and the associated effects on wound outcomes are discussed. © 2017 American Society for Nutrition.

  14. Clinical assessment of wounds and antimicrobial susceptibility ...

    African Journals Online (AJOL)

    A study was conducted at two veterinary surgeries to investigate the common aerobic bacteria associated with dog bite wounds in dogs, and to determine their antimicrobial susceptibilities. From each wound, two swabs were collected for bacterial culture and cytology. A total of 50 wounds from 50 dogs were examined, with ...

  15. The evolution of negative pressure wound therapy: negative pressure wound therapy with instillation.

    Science.gov (United States)

    Wolvos, Tom

    2015-04-01

    Complex wounds pose a considerable burden to patients and the health-care system. The development of negative pressure wound therapy (NPWT) has revolutionised the treatment of these wounds. NPWT helps create a favourable wound healing environment by removing infectious material, decreasing oedema and promoting perfusion and granulation tissue formation. Additionally, NPWT has been reported to help reduce time to wound closure and length of hospital stay. Modifications of this foundation of wound care have added intermittent instillation with a dwell time to NPWT (NPWTi-d). This new system offers more comprehensive wound care through automated wound irrigation, allowing more control over the wound environment and the opportunity to deliver topical wound solutions directly to the affected tissues. A comparison between the two therapies, NPWT and NPWTi-d, is described, and two real-world applications of NPWTi-d are presented.

  16. Emergency Management of Chronic Wounds

    Science.gov (United States)

    2007-01-01

    arteriography if angioplasty , stenting , or bypass are considered. Contrast angiography, although still considered the gold standard [10] of pre-inter...disease Medications (corticosteroids, immunosuppressants etc.) Cigarette smoking Stress ( mechanical /emotional) Inadequate/inappropriate wound care...the process of recanalization valves are damaged, yielding essentially open tubes [24]. Five years after a significant DVT, 40% to 70% of pa- tients

  17. An improvised wound closure system

    NARCIS (Netherlands)

    Lapid, Oren

    2006-01-01

    BACKGROUND: Skin stretching harnesses the same viscoelastic properties of the skin as expansion, with the difference that the forces are applied externally and not internally. An improvised system for wound closure is presented. METHOD: The system is assembled using silicone vascular loops used as

  18. Collagen: Benefits in wound Healing

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Collagen: Benefits in wound Healing. As substrate for haemostasis. As chemotactic to cellular elements. As scaffold for transition to mature collagen production & alignment. Resistant to degradation. As template for cellular attachment, migration and proliferation.

  19. [Efficacy of photodynamic antimicrobial therapy for wound flora and wound healing of pressure sore with pathogen infection].

    Science.gov (United States)

    Wang, Chaoliang; Huang, Sufang; Zhu, Tao; Sun, Xuesheng; Zou, Yong; Wang, Yingzhen

    2014-08-19

    To explore the efficacy of photodynamic antimicrobial therapy in the treatment of pressure sore with pathogen infection. A total of 42 pressure sore patients with pathogen infection were divided randomly into experimental and control groups (n = 21 each). Fufanghuangbai liquid was used for external application with control group. In the experimental group, wound was treated with Fufanghuangbai liquid wet dressing and irradiated by semiconductor laser 30 min late. The distance from semiconductor laser probe to wound site was 10-15 cm, 20 min twice daily, continuous exposure to 7 days for 1 course. The results of bacterial culture and epidermal growth factor (EGF) expression of wound granulation tissue were observed before and after treatment. And the changes of healing rate of pressure sore were measured at post-treatment in each group. The positive rates of bacterial culture, rates of change around wound inflammation, healing rate of days 7 and 14, the high expression of EGF on healing wound granulation tissue was 9.75%, (32.2% ± 5.8%), (89.1% ± 5.6%), (12.4% ± 2.9%), (34.7% ± 3.6%), 14/21 in the treatment group versus 51.2%, (17.8% ± 2.0%), (57.3% ± 2.6%), (5.1% ± 1.1%), (10.5% ± 2.4%), 2/21 in the control group respectively. The inter-group differences were statistically significant (P Photodynamic antimicrobial therapy is an effective method for pressure sore with pathogen infection. Wound healing is promoted through an up-regulation of EGF.

  20. Negative Pressure Wound Therapy on Closed Surgical Wounds With Dead Space

    OpenAIRE

    Suh, Hyunsuk; Lee, A-Young; Park, Eun Jung; Hong, Joon Pio

    2015-01-01

    Background Closed incisional wound surgery frequently leaves dead space under the repaired skin, which results in delayed healing. The purpose of this study was to evaluate the effect of negative pressure wound therapy (NPWT) on incisional wounds with dead space after primary closure by evaluating the fluid volume through the suction drain, blood flow of the skin, tensile strength, and histology of the wounds. Methods Bilateral 25-cm-long incisional wounds with dead space were created on the ...

  1. Wound management in obese patients after median sternotomy using a negativ pressure wound dressing

    OpenAIRE

    Navasardyan, Artashes

    2013-01-01

    Obesity is the most commonly identified risk factor for development of wound infection after median sternotomy. In these patients in the postoperative period, due to overweight, an enormous mechanical stress is exercised on the wound. This leads to an interruption of the continuity of the skin wound and facilitates penetration of the skin flora into the deep wound layers. This increases the risk of patients developing a wound infection (Gardlund A mechanism). A new method for the preventi...

  2. Wound care dressings and choices for care of wounds in the home.

    Science.gov (United States)

    Adkins, Carrie L

    2013-05-01

    Statistics from various resources report that many patients in home healthcare settings have wounds. These vary from surgical, pressure, neuropathic, trauma, stasis, and venous wounds. These require the assessment, knowledge, and expertise of a clinician to assist them with wound care management. The purpose of this article is to identify and categorize types of wound care products appropriate for the various types of wounds that clinicians care for and manage in the home.

  3. Dual therapeutic functions of F-5 fragment in burn wounds: preventing wound progression and promoting wound healing in pigs

    Directory of Open Access Journals (Sweden)

    Ayesha Bhatia

    2016-01-01

    Full Text Available Burn injuries are a leading cause of morbidity including prolonged hospitalization, disfigurement, and disability. Currently there is no Food and Drug Administration-approved burn therapeutics. A clinical distinction of burn injuries from other acute wounds is the event of the so-called secondary burn wound progression within the first week of the injury, in which a burn expands horizontally and vertically from its initial boundary to a larger area. Therefore, an effective therapeutics for burns should show dual abilities to prevent the burn wound progression and thereafter promote burn wound healing. Herein we report that topically applied F-5 fragment of heat shock protein-90α is a dual functional agent to promote burn wound healing in pigs. First, F-5 prevents burn wound progression by protecting the surrounding cells from undergoing heat-induced caspase 3 activation and apoptosis with increased Akt activation. Accordingly, F-5–treated burn and excision wounds show a marked decline in inflammation. Thereafter, F-5 accelerates burn wound healing by stimulating the keratinocyte migration-led reepithelialization, leading to wound closure. This study addresses a topical agent that is capable of preventing burn wound progression and accelerating burn wound healing.

  4. Dual therapeutic functions of F-5 fragment in burn wounds: preventing wound progression and promoting wound healing in pigs.

    Science.gov (United States)

    Bhatia, Ayesha; O'Brien, Kathryn; Chen, Mei; Wong, Alex; Garner, Warren; Woodley, David T; Li, Wei

    2016-01-01

    Burn injuries are a leading cause of morbidity including prolonged hospitalization, disfigurement, and disability. Currently there is no Food and Drug Administration-approved burn therapeutics. A clinical distinction of burn injuries from other acute wounds is the event of the so-called secondary burn wound progression within the first week of the injury, in which a burn expands horizontally and vertically from its initial boundary to a larger area. Therefore, an effective therapeutics for burns should show dual abilities to prevent the burn wound progression and thereafter promote burn wound healing. Herein we report that topically applied F-5 fragment of heat shock protein-90α is a dual functional agent to promote burn wound healing in pigs. First, F-5 prevents burn wound progression by protecting the surrounding cells from undergoing heat-induced caspase 3 activation and apoptosis with increased Akt activation. Accordingly, F-5-treated burn and excision wounds show a marked decline in inflammation. Thereafter, F-5 accelerates burn wound healing by stimulating the keratinocyte migration-led reepithelialization, leading to wound closure. This study addresses a topical agent that is capable of preventing burn wound progression and accelerating burn wound healing.

  5. Dual therapeutic functions of F-5 fragment in burn wounds: preventing wound progression and promoting wound healing in pigs

    Science.gov (United States)

    Bhatia, Ayesha; O’Brien, Kathryn; Chen, Mei; Wong, Alex; Garner, Warren; Woodley, David T.; Li, Wei

    2016-01-01

    Burn injuries are a leading cause of morbidity including prolonged hospitalization, disfigurement, and disability. Currently there is no Food and Drug Administration-approved burn therapeutics. A clinical distinction of burn injuries from other acute wounds is the event of the so-called secondary burn wound progression within the first week of the injury, in which a burn expands horizontally and vertically from its initial boundary to a larger area. Therefore, an effective therapeutics for burns should show dual abilities to prevent the burn wound progression and thereafter promote burn wound healing. Herein we report that topically applied F-5 fragment of heat shock protein-90α is a dual functional agent to promote burn wound healing in pigs. First, F-5 prevents burn wound progression by protecting the surrounding cells from undergoing heat-induced caspase 3 activation and apoptosis with increased Akt activation. Accordingly, F-5–treated burn and excision wounds show a marked decline in inflammation. Thereafter, F-5 accelerates burn wound healing by stimulating the keratinocyte migration-led reepithelialization, leading to wound closure. This study addresses a topical agent that is capable of preventing burn wound progression and accelerating burn wound healing. PMID:27382602

  6. [Chronic wounds as a public health problem].

    Science.gov (United States)

    Situm, Mirna; Kolić, Maja; Redzepi, Gzim; Antolić, Slavko

    2014-10-01

    Chronic wounds represent a significant burden to patients, health care professionals and the entire health care system. Regarding the healing process, wounds can be classified as acute or chronic wounds. A wound is considered chronic if healing does not occur within the expected period according to the wound etiology and localization. Chronic wounds can be classified as typical and atypical. The majority of wounds (95 percent) are typical ones, which include ischemic, neurotrophic and hypostatic ulcers and two separate entities: diabetic foot and decubital ulcers. Eighty percent of chronic wounds localized on lower leg are the result of chronic venous insufficiency, in 5-10 percent the cause is of arterial etiology, whereas the rest are mostly neuropathic ulcers. Chronic wounds significantly decrease the quality of life of patients by requiring continuous topical treatment, causing immobility and pain in a high percentage of patients. Chronic wounds affect elderly population. Chronic leg ulcers affect 0.6-3 percent of those aged over 60, increasing to over 5 percent of those aged over 80. Emergence of chronic wounds is a substantial socioeconomic problem as 1-2 percent of western population will suffer from it. This estimate is expected to rise due to the increasing proportion of elderly population along with the diabetic and obesity epidemic. It has been proved that chronic wounds account for the large proportion of costs in the health care system, even in rich societies. Socioeconomically, the management of chronic wounds reaches a total of 2-4 percent of the health budget in western countries. Treatment costs for some other diseases are not irrelevant, nor are the method and materials used for treating these wounds. Considering etiologic factors, a chronic wound demands a multidisciplinary approach with great efforts of health care professionals to treat it more efficiently, more simply and more painlessly for the patient, as well as more inexpensively for

  7. Use of Multiple Adjunctive Negative Pressure Wound Therapy Modalities to Manage Diabetic Lower-Extremity Wounds.

    Science.gov (United States)

    Cole, Windy E

    2016-01-01

    Objective: Various treatment options exist for wound healing; however, clinical assessment of the patient and the wound environment must be considered before determining an optimal wound treatment plan. Negative pressure wound therapy alone and/or with an instilled topical solution can be effective in adjunctive management of acute and chronic wounds. Hyperbaric oxygen therapy has also been shown to contribute to the wound-healing process. A pilot evaluation using a multistep approach of adjunctive negative pressure wound therapy with instillation and a dwell time, standard negative pressure wound therapy, and hyperbaric oxygen therapy was explored to manage postsurgical, diabetic lower-extremity wounds with a significant bioburden. Methods: Three diabetic patients with lower-extremity ulcers were treated after surgical intervention. Multistep wound therapy consisted of (1) negative pressure wound therapy with instillation of normal saline with a 20-minute dwell time, followed by 2 hours of negative pressure at -150 mm Hg for 3 to 4 days; (2) 1 to 3 weeks of continuous negative pressure at -150 mm Hg; and (3) multiple treatments of hyperbaric oxygen therapy. Results: After surgery, wound closure was achieved within 4 weeks postinitiation of multistep wound therapy. All patients regained limb function and recovered with no long-term sequelae. Conclusions: In these 3 cases, a multistep wound therapy approach after surgery resulted in successful outcomes; however, larger prospective studies are needed to demonstrate the potential efficacy of this approach in the postsurgical management of complex, diabetic lower-extremity wounds.

  8. Perforating Cervical, Thoracic, and Abdominal Wounds.

    Science.gov (United States)

    Risselada, Marije

    2017-11-01

    Most body wall injuries in small animals are caused by bite wounds or vehicular trauma. Penetrating gunshot wounds are less common. Bite wounds are characterized by massive trauma to the body wall with associated defects, but fewer internal injuries, whereas gunshot wounds are associated with a high number of internal injuries. Vehicular accident injuries are caused by blunt force trauma and can lead to both body wall defects and internal organ damage. Impalement injuries are rare and are typically associated with internal damage. Exploratory surgery, herniorrhaphy, and aggressive wound management are recommended in the treatment of these injuries. Published by Elsevier Inc.

  9. Physics of Wound Healing I: Energy Considerations

    CERN Document Server

    Apell, S Peter; Papazoglou, Elisabeth S; Pizziconi, Vincent

    2012-01-01

    Wound healing is a complex process with many components and interrelated processes on a microscopic level. This paper addresses a macroscopic view on wound healing based on an energy conservation argument coupled with a general scaling of the metabolic rate with body mass M as M^{\\gamma} where 0 <{\\gamma}<1. Our three main findings are 1) the wound healing rate peaks at a value determined by {\\gamma} alone, suggesting a concept of wound acceleration to monitor the status of a wound. 2) We find that the time-scale for wound healing is a factor 1/(1 -{\\gamma}) longer than the average internal timescale for producing new material filling the wound cavity in corresondence with that it usually takes weeks rather than days to heal a wound. 3) The model gives a prediction for the maximum wound mass which can be generated in terms of measurable quantities related to wound status. We compare our model predictions to experimental results for a range of different wound conditions (healthy, lean, diabetic and obses...

  10. Challenges in the Treatment of Chronic Wounds.

    Science.gov (United States)

    Frykberg, Robert G; Banks, Jaminelli

    2015-09-01

    Significance: Chronic wounds include, but are not limited, to diabetic foot ulcers, venous leg ulcers, and pressure ulcers. They are a challenge to wound care professionals and consume a great deal of healthcare resources around the globe. This review discusses the pathophysiology of complex chronic wounds and the means and modalities currently available to achieve healing in such patients. Recent Advances: Although often difficult to treat, an understanding of the underlying pathophysiology and specific attention toward managing these perturbations can often lead to successful healing. Critical Issues: Overcoming the factors that contribute to delayed healing are key components of a comprehensive approach to wound care and present the primary challenges to the treatment of chronic wounds. When wounds fail to achieve sufficient healing after 4 weeks of standard care, reassessment of underlying pathology and consideration of the need for advanced therapeutic agents should be undertaken. However, selection of an appropriate therapy is often not evidence based. Future Directions: Basic tenets of care need to be routinely followed, and a systematic evaluation of patients and their wounds will also facilitate appropriate care. Underlying pathologies, which result in the failure of these wounds to heal, differ among various types of chronic wounds. A better understanding of the differences between various types of chronic wounds at the molecular and cellular levels should improve our treatment approaches, leading to better healing rates, and facilitate the development of new more effective therapies. More evidence for the efficacy of current and future advanced wound therapies is required for their appropriate use.

  11. Wound bed preparation from a clinical perspective

    Directory of Open Access Journals (Sweden)

    A S Halim

    2012-01-01

    Full Text Available Wound bed preparation has been performed for over two decades, and the concept is well accepted. The ′TIME′ acronym, consisting of tissue debridement, i nfection or inflammation, moisture balance and edge effect, has assisted clinicians systematically in wound assessment and management. While the focus has usually been concentrated around the wound, the evolving concept of wound bed preparation promotes the treatment of the patient as a whole. This article discusses wound bed preparation and its clinical management components along with the principles of advanced wound care management at the present time. Management of tissue necrosis can be tailored according to the wound and local expertise. It ranges from simple to modern techniques like wet to dry dressing, enzymatic, biological and surgical debridement. Restoration of the bacterial balance is also an important element in managing chronic wounds that are critically colonized. Achieving a balance moist wound will hasten healing and correct biochemical imbalance by removing the excessive enzymes and growth factors. This can be achieved will multitude of dressing materials. The negative pressure wound therapy being one of the great breakthroughs. The progress and understanding on scientific basis of the wound bed preparation over the last two decades are discussed further in this article in the clinical perspectives.

  12. Laminin receptor 1 is differentially expressed in thoracic and limb wounds in the horse.

    Science.gov (United States)

    Miragliotta, Vincenzo; Lussier, Jacques G; Theoret, Christine L

    2009-02-01

    Healing of wounds located on the distal limbs of horses is often complicated by retarded epithelialization and the development of exuberant granulation tissue (proud flesh). Treatments that definitively resolve this pathological process are still unavailable. Molecular studies of the repair mechanism might contribute to the development of new therapeutic strategies. The study presented herein aimed to clone the full length cDNA and to study the spatio-temporal expression profile of mRNA and protein for LAMR1, previously attributed a role in wound epithelialization, during the repair of body and limb wounds in the horse. Cloning was achieved by screening a cDNA library previously derived from 7-day wound biopsies. Expression was studied in unwounded skin and in samples from 1-, 2-, 3-, 4- and 6-week-old wounds of the body and limb. Temporal gene expression was determined by real time polymerase chain reaction (RT-PCR) while protein expression was mapped immunohistochemically. Full-length cDNA for equine LAMR1 was shown to be highly similar to that of other species. The mRNA expression of LAMR1 was significantly up-regulated only in thoracic wounds, 4 and 6 weeks following wounding (upon epithelialization). Cutaneous wounding induced protein expression at both locations. Our data suggest that up-regulation of LAMR1 protein might favour epithelialization during wound healing. However, its interaction with ligands other than laminin complicates data interpretation. Future studies should quantitatively verify the temporal expression of this protein in order to provide the basis for targeted therapies that might enhance epithelialization.

  13. [Suspected anaphylaxis by wound treatment with polyhexanide derivate wound products].

    Science.gov (United States)

    Schrøder, Morten A; Kirketerp-Møller, Klaus; Winther, Lone

    2014-12-15

    Only four cases of anaphylaxis triggered by polyhexanide have been reported in the literature. We report a case of anaphylaxis in a Danish patient treated with polyhexanide derivate (Prontosan) wound products. We emphasise the importance of intramuscular injection of adrenaline as part of the treatment protocol in the initial phase of anaphylaxis and stress the importance of being aware of polyhexanide as a potential trigger of anaphylaxis.

  14. Open Wound Drainage Versus Wound Excision on the Modern Battlefield

    Science.gov (United States)

    1988-02-01

    penicillin coverage to eliminate the threat of invasive bacteremia by hemolytic streptococcus , presumably produced conditions that insured unimpeded...pyemia, septicemia and erysipelas remained major causes of death in the war wounded (10). Friedrich originated the idea of excising the bacteria...hemolytic streptococcus in 10 to 15% of cases, but after a week in the hospital over 90% of w-unds were infected with this bacteria (12,13), and

  15. The curvature coordinate system

    DEFF Research Database (Denmark)

    Almegaard, Henrik

    2007-01-01

    The paper describes a concept for a curvature coordinate system on regular curved surfaces from which faceted surfaces with plane quadrangular facets can be designed. The lines of curvature are used as parametric lines for the curvature coordinate system on the surface. A new conjugate set of lines......, called middle curvature lines, is introduced. These lines define the curvature coordinate system. Using the curvature coordinate system, the surface can be conformally mapped on the plane. In this mapping, elliptic sections are mapped as circles, and hyperbolic sections are mapped as equilateral...... hyperbolas. This means that when a plane orthogonal system of curves for which the vertices in a mesh always lie on a circle is mapped on a surface with positive Gaussian curvature using inverse mapping, and the mapped vertices are connected by straight lines, this network will form a faceted surface...

  16. Environmental Compliance Issue Coordination

    Science.gov (United States)

    An order to establish the Department of Energy (DOE) requirements for coordination of significant environmental compliance issues to ensure timely development and consistent application of Departmental environmental policy and guidance

  17. Supercritical Airfoil Coordinates

    Data.gov (United States)

    National Aeronautics and Space Administration — Rectangular Supercritical Wing (Ricketts) - design and measured locations are provided in an Excel file RSW_airfoil_coordinates_ricketts.xls . One sheet is with Non...

  18. Metric Coordinate Systems

    OpenAIRE

    Calcaterra, Craig; Boldt, Axel; Green, Michael; Bleecker, David

    2002-01-01

    Coordinate systems are defined on general metric spaces with the purpose of generalizing vector fields on a manifold. Conversion formulae are available between metric and Cartesian coordinates on a Hilbert space. Nagumo's Invariance Theorem is invoked to prove the analogue of the classical Cauchy-Lipschitz Theorem for vector fields on a locally compact coordinatized space. A metric space version of Nagumo's Theorem is one consequence. Examples are given throughout.

  19. Cefazolin concentration in surgically created wounds treated with negative pressure wound therapy compared to surgically created wounds treated with nonadherent wound dressings.

    Science.gov (United States)

    Coutin, Julia V; Lanz, Otto I; Magnin-Bissel, Geraldine C; Ehrich, Marion F; Miller, Emily I; Werre, Stephen R; Riegel, Thomas O

    2015-01-01

    To compare cefazolin concentrations in biopsied tissue samples collected from surgically created wounds treated with negative pressure wound therapy to those collected from surgically created wounds treated with nonadherent dressings. Prospective, controlled, experimental study. Adult female spayed Beagles (n = 12). Full thickness cutaneous wounds were created on each antebrachium (n = 24). Immediately after surgery, cefazolin (22 mg/kg intravenously [IV]) was administered to each dog and continued every 8 hours during the study. The right wound was randomly assigned to group I or group II whereas the wound on the contralateral antebrachium was assigned to the other group. Group I wounds were treated with negative pressure wound therapy (NPWT) and group II wounds were treated with nonadherent dressings for 3 days. Dressings were changed and tissue biopsies obtained from wound beds at 24 hours intervals for both groups. Cefazolin wound tissue and plasma concentrations were measured by liquid chromatography mass spectrometry (LC-MS/MS). Blood samples for measuring plasma cefazolin concentrations were collected before biopsy sampling. At the time of surgery and at each subsequent bandage change, wound beds were swabbed and submitted for aerobic and anaerobic culture. After initiating cefazolin treatment, wound tissue antibiotic concentrations between treatment groups were not significantly different at any sampling time. Similarly, after initiating cefazolin treatment, plasma cefazolin concentrations were not significantly different at any sampling time for individual dogs. Using a canine experimental model, NPWT treatment of surgically created wounds does not statistically impact cefazolin tissue concentrations when compared with conventional nonadherent bandage therapy. © Copyright 2014 by The American College of Veterinary Surgeons.

  20. Rapid identification of slow healing wounds.

    Science.gov (United States)

    Jung, Kenneth; Covington, Scott; Sen, Chandan K; Januszyk, Michael; Kirsner, Robert S; Gurtner, Geoffrey C; Shah, Nigam H

    2016-01-01

    Chronic nonhealing wounds have a prevalence of 2% in the United States, and cost an estimated $50 billion annually. Accurate stratification of wounds for risk of slow healing may help guide treatment and referral decisions. We have applied modern machine learning methods and feature engineering to develop a predictive model for delayed wound healing that uses information collected during routine care in outpatient wound care centers. Patient and wound data was collected at 68 outpatient wound care centers operated by Healogics Inc. in 26 states between 2009 and 2013. The dataset included basic demographic information on 59,953 patients, as well as both quantitative and categorical information on 180,696 wounds. Wounds were split into training and test sets by randomly assigning patients to training and test sets. Wounds were considered delayed with respect to healing time if they took more than 15 weeks to heal after presentation at a wound care center. Eleven percent of wounds in this dataset met this criterion. Prognostic models were developed on training data available in the first week of care to predict delayed healing wounds. A held out subset of the training set was used for model selection, and the final model was evaluated on the test set to evaluate discriminative power and calibration. The model achieved an area under the curve of 0.842 (95% confidence interval 0.834-0.847) for the delayed healing outcome and a Brier reliability score of 0.00018. Early, accurate prediction of delayed healing wounds can improve patient care by allowing clinicians to increase the aggressiveness of intervention in patients most at risk. © 2015 by the Wound Healing Society.

  1. 49 CFR 1544.215 - Security coordinators.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 9 2010-10-01 2010-10-01 false Security coordinators. 1544.215 Section 1544.215 Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY AIRCRAFT OPERATOR SECURITY: AIR CARRIERS AND...

  2. 49 CFR 1548.13 - Security coordinators.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 9 2010-10-01 2010-10-01 false Security coordinators. 1548.13 Section 1548.13 Transportation Other Regulations Relating to Transportation (Continued) TRANSPORTATION SECURITY ADMINISTRATION, DEPARTMENT OF HOMELAND SECURITY CIVIL AVIATION SECURITY INDIRECT AIR CARRIER SECURITY § 1548.13 Security...

  3. 24 CFR 700.130 - Service coordinator.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Service coordinator. 700.130 Section 700.130 Housing and Urban Development Regulations Relating to Housing and Urban Development...) Assist the grant recipient in building informal support networks with neighbors, friends and family; and...

  4. Magnetic Coordinate Systems

    Science.gov (United States)

    Laundal, K. M.; Richmond, A. D.

    2017-03-01

    Geospace phenomena such as the aurora, plasma motion, ionospheric currents and associated magnetic field disturbances are highly organized by Earth's main magnetic field. This is due to the fact that the charged particles that comprise space plasma can move almost freely along magnetic field lines, but not across them. For this reason it is sensible to present such phenomena relative to Earth's magnetic field. A large variety of magnetic coordinate systems exist, designed for different purposes and regions, ranging from the magnetopause to the ionosphere. In this paper we review the most common magnetic coordinate systems and describe how they are defined, where they are used, and how to convert between them. The definitions are presented based on the spherical harmonic expansion coefficients of the International Geomagnetic Reference Field (IGRF) and, in some of the coordinate systems, the position of the Sun which we show how to calculate from the time and date. The most detailed coordinate systems take the full IGRF into account and define magnetic latitude and longitude such that they are constant along field lines. These coordinate systems, which are useful at ionospheric altitudes, are non-orthogonal. We show how to handle vectors and vector calculus in such coordinates, and discuss how systematic errors may appear if this is not done correctly.

  5. [Coordination and donation].

    Science.gov (United States)

    Elizalde, J; Lorente, M

    2006-01-01

    The progressive incorporation of organ transplants as a therapeutic resource resulted in organisational adaptation and overall transplant management, leading to the emergence of the figure of the transplant coordinator in the mid-1980s. In Spain, the National Organisation of Transplants (Organización Nacional de Transplantes - ONT) was created, establishing a system - called the "Spanish model" - based on a network of coordinators at three levels: national, the autonomous community and the hospital. This organisational structure is a point of reference at the world level. The prevalence of the Intensive Medicine specialisation amongst hospital transplant coordinators is remarkable. The majority of organs proceed from brain-dead patients with beating hearts and this requires the infrastructure offered by intensive care units. The functions of the coordinator can be summarised in guaranteeing a synchrony of all the elements and teams that come together in an organisational chain that has come to be called the "process of donation". Schematically, the crucial points that the hospital coordinator develops are the following: - Detection of the potential donor. - Maintenance of the donor. - Diagnosis of brain death. - Family consent. - Preparation of the hospital logistics. - Helping the relatives. - Direct involvement in the Program of Guarantee of Quality. - Person of reference in any activity related to the transplant. It would be desirable to achieve the creation of transplant coordination teams, with univocal messages, professionalism and a permanent input of the so-called "human factor", which is so necessary and also so close to the transplant world.

  6. Wound healing and all-cause mortality in 958 wound patients treated in home care

    DEFF Research Database (Denmark)

    Zarchi, Kian; Martinussen, Torben; Jemec, Gregor B. E.

    2015-01-01

    Skin wounds are associated with significant morbidity and mortality. Data are, however, not readily available for benchmarking, to allow prognostic evaluation, and to suggest when involvement of wound-healing experts is indicated. We, therefore, conducted an observational cohort study...... to investigate wound healing and all-cause mortality associated with different types of skin wounds. Consecutive skin wound patients who received wound care by home-care nurses from January 2010 to December 2011 in a district in Eastern Denmark were included in this study. Patients were followed until wound...... healing, death, or the end of follow-up on December 2012. In total, 958 consecutive patients received wound care by home-care nurses, corresponding to a 1-year prevalence of 1.2% of the total population in the district. During the study, wound healing was achieved in 511 (53.3%), whereas 90 (9.4%) died...

  7. Management of minor acute cutaneous wounds: importance of wound healing in a moist environment.

    Science.gov (United States)

    Korting, H C; Schöllmann, C; White, R J

    2011-02-01

    Moist wound care has been established as standard therapy for chronic wounds with impaired healing. Healing in acute wounds, in particular in minor superficial acute wounds - which indeed are much more numerous than chronic wounds - is often taken for granted because it is assumed that in those wounds normal phases of wound healing should run per se without any problems. But minor wounds such as small cuts, scraps or abrasions also need proper care to prevent complications, in particular infections. Local wound care with minor wounds consists of thorough cleansing with potable tap water or normal saline followed by the application of an appropriate dressing corresponding to the principles of moist wound treatment. In the treatment of smaller superficial wounds, it appears advisable to limit the choice of dressing to just a few products that fulfil the principles of moist wound management and are easy to use. Hydroactive colloid gels combining the attributes of hydrocolloids and hydrogels thus being appropriate for dry and exuding wounds appear especially suitable for this purpose - although there is still a lack of data from systematic studies on the effectiveness of these preparations. © 2010 The Authors. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology.

  8. Incisional Negative Pressure Wound Therapy in High Risk Patients Undergoing Panniculectomy: A Prospective Randomized Controlled Trial

    Science.gov (United States)

    2017-01-03

    Complications Wounds; Negative Pressure Wound Therapy; Wound Healing Delayed; Incisional; Panniculectomy; Incisional Negative Pressure Wound Therapy; Incisional Vac; Wound Vac; Obese; Renal Failure; Kidney Transplant; Complications; Wound Healing Complication

  9. Critical Role of Transforming Growth Factor Beta in Different Phases of Wound Healing

    Science.gov (United States)

    Pakyari, Mohammadreza; Farrokhi, Ali; Maharlooei, Mohsen Khosravi; Ghahary, Aziz

    2013-01-01

    Significance This review highlights the critical role of transforming growth factor beta (TGF-β)1–3 within different phases of wound healing, in particular, late-stage wound healing. It is also very important to identify the TGF-β1–controlling factors involved in slowing down the healing process upon wound epithelialization. Recent Advances TGF-β1, as a growth factor, is a known proponent of dermal fibrosis. Several strategies to modulate or regulate TGF's actions have been thoroughly investigated in an effort to create successful therapies. This study reviews current discourse regarding the many roles of TGF-β1 in wound healing by modulating infiltrated immune cells and the extracellular matrix. Critical Issues It is well established that TGF-β1 functions as a wound-healing promoting factor, and thereby if in excess it may lead to overhealing outcomes, such as hypertrophic scarring and keloid. Thus, the regulation of TGF-β1 in the later stages of the healing process remains as critical issue of which to better understand. Future Directions One hypothesis is that cell communication is the key to regulate later stages of wound healing. To elucidate the role of keratinocyte/fibroblast cross talk in controlling the later stages of wound healing we need to: (1) identify those keratinocyte-released factors which would function as wound-healing stop signals, (2) evaluate the functionality of these factors in controlling the outcome of the healing process, and (3) formulate topical vehicles for these antifibrogenic factors to improve or even prevent the development of hypertrophic scarring and keloids as a result of deep trauma, burn injuries, and any type of surgical incision. PMID:24527344

  10. Current management of wound healing

    DEFF Research Database (Denmark)

    Gottrup, F; Karlsmark, T

    2009-01-01

    While the understanding of wound pathophysiology has progressed considerably over the past decades the improvements in clinical treatment has occurred to a minor degree. During the last years, however, new trends and initiatives have been launched, and we will continue to attain new information...... in the next decade. It is the hope that increasing parts of the new knowledge from basic wound healing research will be implemented in daily clinical practice. The development of new treatment products will also continue, and especially new technologies with combined types of dressing materials or dressing...... containing active substances will be accentuated. Further developments in the management structure and education will also continue and consensus of treatment guidelines, recommendations and organization models will hopefully be achieved....

  11. Wound Dressing in Maxillofacial Trauma.

    Science.gov (United States)

    1979-10-31

    E. Cutright, Commander, Institute of Dental Research. .1 !!. -𔃾 -- 𔄁 - .4. o - o - .- ° .oo -° °° °. ,.. .. . - . . . . o o . . . o° . . ° o...agent, epinaphrine is used mostly in dental surgical procedures. Gingi-Pak (Gingi-Pak Laboratories) is a dental retraction cord which is available with...rapidly. This may be the release required for hemostatic action. The utility as a vasoconstrictor in wound dressing is questionable, and the duffusion

  12. Determination of effective miRNAs in wound healing in an experimental Rat Model.

    Science.gov (United States)

    Coskunpinar, E; Arkan, H; Dedeoglu, B G; Aksoz, I; Polat, E; Araz, T; Aydos, A; Oztemur, Y; Akbas, F; Onaran, I

    2015-12-24

    The larvae of Lucilia sericata have been used for centuries as medicinal maggots in the healing of wounds. The present study aimed to screen potential microRNAs related to ES-induced wound healing in rat skin wounds and to investigate the potential mechanisms contributing to accelerated wound healing. Healthy, male, 12 weeks old Wistar albino rats weighing 250-300 g were supplied by the Animal Experimental Center. All animal studies were performed in accordance with the NIH Guide for the Care and Use of Laboratory Animals. Wistar albino rats were treated by ES after post wounding and the differentially expressed miRNAs in wound biopsies were screened by microarray analysis at the end of treatments for 4,7 and 10 days. In addition, bioinformatics approaches were used to identify the potential target genes of differentially expressed miRNAs and the functions of their target genes. We found a significant up-regulation of rno-miR-99a* and rno-mir-877 in response to ES treatment. Further investigation of rno-miR-99a* and rno-mir-877 and their target genes (TGFa, TNF, TAGLN, MAPK1, MMP-9) implicated in present study could provide new insight for an understanding lead to the development of new treatment strategies. The identified miRNAs can be new biomarkers for ES- induced wound healing.

  13. Genome-wide expression analysis of wounded skin reveals novel genes involved in angiogenesis.

    Science.gov (United States)

    Brönneke, Simone; Brückner, Bodo; Söhle, Jörn; Siegner, Ralf; Smuda, Christoph; Stäb, Franz; Wenck, Horst; Kolbe, Ludger; Grönniger, Elke; Winnefeld, Marc

    2015-07-01

    Wound healing is a multistage process involving collaborative efforts of different cell types and distinct cellular functions. Among others, the high metabolic activity at the wound site requires the formation and sprouting of new blood vessels (angiogenesis) to ensure an adequate supply of oxygen and nutrients for a successful healing process. Thus, a cutaneous wound healing model was established to identify new factors that are involved in vascular formation and remodeling in human skin after embryonic development. By analyzing global gene expression of skin biopsies obtained from wounded and unwounded skin, we identified a small set of genes that were highly significant differentially regulated in the course of wound healing. To initially investigate whether these genes might be involved in angiogenesis, we performed siRNA experiments and analyzed the knockdown phenotypes using a scratch wound assay which mimics cell migration and proliferation in vitro. The results revealed that a subset of these genes influence cell migration and proliferation in primary human endothelial cells (EC). Furthermore, histological analyses of skin biopsies showed that two of these genes, ALBIM2 and TMEM121, are colocalized with CD31, a well known EC marker. Taken together, we identified new genes involved in endothelial cell biology, which might be relevant to develop therapeutics not only for impaired wound healing but also for chronic inflammatory disorders and/or cardiovascular diseases.

  14. Research Techniques Made Simple: Analysis of Collective Cell Migration Using the Wound Healing Assay.

    Science.gov (United States)

    Grada, Ayman; Otero-Vinas, Marta; Prieto-Castrillo, Francisco; Obagi, Zaidal; Falanga, Vincent

    2017-02-01

    Collective cell migration is a hallmark of wound repair, cancer invasion and metastasis, immune responses, angiogenesis, and embryonic morphogenesis. Wound healing is a complex cellular and biochemical process necessary to restore structurally damaged tissue. It involves dynamic interactions and crosstalk between various cell types, interaction with extracellular matrix molecules, and regulated production of soluble mediators and cytokines. In cutaneous wound healing, skin cells migrate from the wound edges into the wound to restore skin integrity. Analysis of cell migration in vitro is a useful assay to quantify alterations in cell migratory capacity in response to experimental manipulations. Although several methods exist to study cell migration (such as Boyden chamber assay, barrier assays, and microfluidics-based assays), in this short report we will explain the wound healing assay, also known as the "in vitro scratch assay" as a simple, versatile, and cost-effective method to study collective cell migration and wound healing. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Microbial profile of canine persistent wound infections

    Directory of Open Access Journals (Sweden)

    A. Padhy

    2014-04-01

    Full Text Available Aim: To analyse the microbial profile of canine persistent wound infections. Materials and Methods: The total wound samples (n=172 taken from both traumatic (140 and post-surgical (32 persistent wounds in canines were processed for routine microbial isolation and identification during a period of 15 months. Results: Staphylococcus intermedius was found to be the predominant isolate from all types of wounds under study. It was followed by Staphylococcus aureus, Pseudomonas aeruginosa, E. coli, Pasteurella spp., Corynaebacterium spp. and Bacillus spp. From different traumatic wounds of dogs, S. intermedius (92/140=65.7% and from surgical wounds, P. aeruginosa (24/32=75% were found to be the predominant isolates recovered whereas the most commonly isolated bacterial genus in both traumatic and surgical wounds of dogs was Staphylococcus spp. Conclusion: Canine wounds are polymicrobial in nature. Hence proper microbial laboratory diagnosis and presence of multiple organisms in a wound are to be taken into consideration for effective treatment of persistent wound infections in dogs.

  16. Biofilm-infected wounds in a dog.

    Science.gov (United States)

    Swanson, Elizabeth A; Freeman, Lynetta J; Seleem, Mohamed N; Snyder, Paul W

    2014-03-15

    A 4-year-old spayed female Mastiff was evaluated for treatment of chronic nonhealing pressure wounds over both elbow regions resulting from attempts at hypertrophic callus excision. The wound bed granulation tissue was mottled red and yellow with hyperemic, rolled epithelial edges. The right wound communicated with a large fluid pocket along the thoracic wall. The dog had an inflammatory leukogram with a left shift. The wounds were debrided, and tissue specimens were collected for histologic evaluation, microbial culture, and bacterial identification by means of molecular diagnostic techniques. The left wound was closed immediately. Calcium alginate rope with silver was packed into the right wound. Vacuum-assisted closure was applied for 6 days. Debridement was repeated, and a thoracodorsal axial pattern flap was used to cover the wound. Systemic treatment with antimicrobials was initiated, and pressure over the elbow regions was relieved. Bacterial biofilms were identified histologically in tissue specimens from both wounds. Staphylococcus intermedius, Staphylococcus epidermidis, and Streptococcus canis were cultured and identified by 16S rRNA fragment sequencing. Pyrosequencing identified multiple bacterial species and no fungal organisms. Both wounds healed successfully. Biofilms are implicated in infected orthopedic implants in veterinary patients; however, this is the first report of a bacterial biofilm in chronic wounds in a dog. In human wound care, extensive debridement is performed to disrupt the biofilm; a multimodal treatment approach is recommended to delay reformation and help clear the infection. In this case, biofilm reformation was prevented by systemic treatment with antimicrobials, by reducing local pressure on the wounds, and by wound closure.

  17. Bacterial Contribution in Chronicity of Wounds.

    Science.gov (United States)

    Rahim, Kashif; Saleha, Shamim; Zhu, Xudong; Huo, Liang; Basit, Abdul; Franco, Octavio Luiz

    2017-04-01

    A wound is damage of a tissue usually caused by laceration of a membrane, generally the skin. Wound healing is accomplished in three stages in healthy individuals, including inflammatory, proliferative, and remodeling stages. Healing of wounds normally starts from the inflammatory phase and ends up in the remodeling phase, but chronic wounds remain in an inflammatory stage and do not show progression due to some specific reasons. Chronic wounds are classified in different categories, such as diabetic foot ulcer (DFU), venous leg ulcers (VLU) and pressure ulcer (PU), surgical site infection (SSI), abscess, or trauma ulcers. Globally, the incidence rate of DFU is 1-4 % and prevalence rate is 5.3-10.5 %. However, colonization of pathogenic bacteria at the wound site is associated with wound chronicity. Most chronic wounds contain more than one bacterial species and produce a synergetic effect that results in previously non-virulent bacterial species becoming virulent and causing damage to the host. While investigating bacterial diversity in chronic wounds, Staphylococcus, Pseudomonas, Peptoniphilus, Enterobacter, Stenotrophomonas, Finegoldia, and Serratia were found most frequently in chronic wounds. Recently, it has been observed that bacteria in chronic wounds develop biofilms that contribute to a delay in healing. In a mature biofilm, bacteria grow slowly due to deficiency of nutrients that results in the resistance of bacteria to antibiotics. The present review reflects the reasons why acute wounds become chronic. Interesting findings include the bacterial load, which forms biofilms and shows high-level resistance toward antibiotics, which is a threat to human health in general and particularly to some patients who have acute wounds.

  18. Wound contraction and macro-deformation during negative pressure therapy of sternotomy wounds

    Directory of Open Access Journals (Sweden)

    Ingemansson Richard

    2010-09-01

    Full Text Available Abstract Background Negative pressure wound therapy (NPWT is believed to initiate granulation tissue formation via macro-deformation of the wound edge. However, only few studies have been performed to evaluate this hypothesis. The present study was performed to investigate the effects of NPWT on wound contraction and wound edge tissue deformation. Methods Six pigs underwent median sternotomy followed by magnetic resonance imaging in the transverse plane through the thorax and sternotomy wound during NPWT at 0, -75, -125 and -175 mmHg. The lateral width of the wound and anterior-posterior thickness of the wound edge was measured in the images. Results The sternotomy wound decreased in size following NPWT. The lateral width of the wound, at the level of the sternum bone, decreased from 39 ± 7 mm to 30 ± 6 mm at -125 mmHg (p = 0.0027. The greatest decrease in wound width occurred when switching from 0 to -75 mmHg. The level of negative pressure did not affect wound contraction (sternum bone: 32 ± 6 mm at -75 mmHg and 29 ± 6 mm at -175 mmHg, p = 0.0897. The decrease in lateral wound width during NPWT was greater in subcutaneous tissue (14 ± 2 mm than in sternum bone (9 ± 2 mm, resulting in a ratio of 1.7 ± 0.3 (p = 0.0423, suggesting macro-deformation of the tissue. The anterior-posterior thicknesses of the soft tissue, at 0.5 and 2.5 cm laterally from the wound edge, were not affected by negative pressure. Conclusions NPWT contracts the wound and causes macro-deformation of the wound edge tissue. This shearing force in the tissue and at the wound-foam interface may be one of the mechanisms by which negative pressure delivery promotes granulation tissue formation and wound healing.

  19. Broad-Spectrum Inhibition of the CC-Chemokine Class Improves Wound Healing and Wound Angiogenesis.

    Science.gov (United States)

    Ridiandries, Anisyah; Bursill, Christina; Tan, Joanne

    2017-01-13

    Angiogenesis is involved in the inflammation and proliferation stages of wound healing, to bring inflammatory cells to the wound and provide a microvascular network to maintain new tissue formation. An excess of inflammation, however, leads to prolonged wound healing and scar formation, often resulting in unfavourable outcomes such as amputation. CC-chemokines play key roles in the promotion of inflammation and inflammatory-driven angiogenesis. Therefore, inhibition of the CC-chemokine class may improve wound healing. We aimed to determine if the broad-spectrum CC-chemokine inhibitor "35K" could accelerate wound healing in vivo in mice. In a murine wound healing model, 35K protein or phosphate buffered saline (PBS, control) were added topically daily to wounds. Cohorts of mice were assessed in the early stages (four days post-wounding) and in the later stages of wound repair (10 and 21 days post-wounding). Topical application of the 35K protein inhibited CC-chemokine expression (CCL5, CCL2) in wounds and caused enhanced blood flow recovery and wound closure in early-mid stage wounds. In addition, 35K promoted neovascularisation in the early stages of wound repair. Furthermore, 35K treated wounds had significantly lower expression of the p65 subunit of NF-κB, a key inflammatory transcription factor, and augmented wound expression of the pro-angiogenic and pro-repair cytokine TGF-β. These findings show that broad-spectrum CC-chemokine inhibition may be beneficial for the promotion of wound healing.

  20. Modern and Convensional Wound Dressing to Interleukin 1 and Interleukin 6 in Diabetic wound

    Directory of Open Access Journals (Sweden)

    Werna Nontji

    2015-04-01

    Full Text Available Introduction:Holistic wound care is one of the ways to prevent gangrene and amputation, modern wound dressing is more effective than convensional with increasing transforming growth factor and cytokine, especially interleukin. This study aims to identify the effectiveness of Modern and Convensional Wound Dressing to Interleukin 1 (IL-1 and Interleukin 6 (IL-6 in Diabetic wound. Method:A Quasi eksperimental pre-post with control group design was used. The intervention given was modern wound dressing and Control group by convensional wound dressing, This study was conducted in Makassar with 32 samples (16 in intervention group and 16 in control group. Result: The result of Pooled T- test showed that p = 0.00 (p < 0.05, it means that there was signifi cant correlation between modern wound dressing to IL-6 and IL-1 than Convensional wound dressing. Discussion: Process of wound healing was produced growth factor and cytokine (IL-1 and IL-6, it will stimulated by wound dressing, modern wound dressing (Calcium alginat can absorb wound drainage, non oklusive, non adhesif, and autolytic debridement. Keywords: Modern wound dressing, Interleukin 1 (IL-1, Interleukin 6 (IL-6

  1. Adjuvant use of acoustic pressure wound therapy for treatment of chronic wounds: a retrospective analysis.

    Science.gov (United States)

    Cole, Pamela S; Quisberg, Jennifer; Melin, M Mark

    2009-01-01

    Small studies have indicated that the addition of acoustic pressure wound therapy (APWT) to conventional wound care may hasten healing of chronic wounds. We evaluated our early clinical experience using APWT as an adjunct to conventional wound care. The study was a retrospective chart review of consecutive patients receiving APWT in addition to conventional wound care in a hospital-based, primarily outpatient setting. Medical records of all patients treated with APWT between August 2006 and October 2007 were reviewed. Analysis included the 41 patients with 52 wounds who received APWT at least 2 times per week during the study period. Statistical comparisons were made for wound dimensions, tissue characteristics, and pain at start versus end of APWT. Thirty-eight percent of wounds (N = 20) healed completely with a mean 6.8 weeks of APWT. Median wound area and volume decreased significantly (88% [P wounds with greater than 75% granulation tissue increased from 26% (n = 12) to 80% (n = 41) (P wounds (P = .006). This early experience supplementing conventional wound care with APWT suggests it may promote healing in chronic wounds, where the ordered cellular and molecular processes leading to healing have stalled.

  2. Wound Blush Obtainment Is the Most Important Angiographic Endpoint for Wound Healing.

    Science.gov (United States)

    Utsunomiya, Makoto; Takahara, Mitsuyoshi; Iida, Osamu; Yamauchi, Yasutaka; Kawasaki, Daizo; Yokoi, Yoshiaki; Soga, Yoshimistu; Ohura, Norihiko; Nakamura, Masato

    2017-01-23

    This study aimed to assess the optimal angiographic endpoint of endovascular therapy (EVT) for wound healing. Several reports have demonstrated acceptable patency and limb salvage rates following infrapopliteal interventions for the treatment of critical limb ischemia (CLI). However, the optimal angiographic endpoint of EVT remains unclear. We conducted a subanalysis of the prospective multicenter OLIVE (Endovascular Treatment for Infrainguinal Vessels in Patients with Critical Limb Ischemia) registry investigation assessing patients who received infrainguinal EVT for CLI. We analyzed data from 185 limbs with ischemic ulcerations classified as Rutherford class 5 or 6, managed with EVT alone (i.e., not undergoing bypass surgery). The wound healing rate after EVT was estimated by the Kaplan-Meier method. The association between final angiographic data and wound healing was assessed employing a Cox proportional hazards model. The overall wound healing rate was 73.5%. The probabilities of wound healing in patients with wound blush obtainment was significantly higher than that of those without wound blush (79.6% vs. 46.5%; p = 0.01). In the multivariate analysis, wound blush obtainment was an independent predictor of wound healing. The presence of wound blush after EVT is significantly associated with wound healing. Wound blush as an angiographic endpoint for EVT may serve as a novel predictor of wound healing in patients with CLI. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  3. Point-of-care wound visioning technology: Reproducibility and accuracy of a wound measurement app.

    Directory of Open Access Journals (Sweden)

    Sheila C Wang

    Full Text Available Current wound assessment practices are lacking on several measures. For example, the most common method for measuring wound size is using a ruler, which has been demonstrated to be crude and inaccurate. An increase in periwound temperature is a classic sign of infection but skin temperature is not always measured during wound assessments. To address this, we have developed a smartphone application that enables non-contact wound surface area and temperature measurements. Here we evaluate the inter-rater reliability and accuracy of this novel point-of-care wound assessment tool.The wounds of 87 patients were measured using the Swift Wound app and a ruler. The skin surface temperature of 37 patients was also measured using an infrared FLIR™ camera integrated with the Swift Wound app and using the clinically accepted reference thermometer Exergen DermaTemp 1001. Accuracy measurements were determined by assessing differences in surface area measurements of 15 plastic wounds between a digital planimeter of known accuracy and the Swift Wound app. To evaluate the impact of training on the reproducibility of the Swift Wound app measurements, three novice raters with no wound care training, measured the length, width and area of 12 plastic model wounds using the app. High inter-rater reliabilities (ICC = 0.97-1.00 and high accuracies were obtained using the Swift Wound app across raters of different levels of training in wound care. The ruler method also yielded reliable wound measurements (ICC = 0.92-0.97, albeit lower than that of the Swift Wound app. Furthermore, there was no statistical difference between the temperature differences measured using the infrared camera and the clinically tested reference thermometer.The Swift Wound app provides highly reliable and accurate wound measurements. The FLIR™ infrared camera integrated into the Swift Wound app provides skin temperature readings equivalent to the clinically tested reference thermometer

  4. 78 FR 32698 - Shipping Coordinating Committee; Notice of Committee Meeting

    Science.gov (United States)

    2013-05-31

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF STATE Shipping Coordinating Committee; Notice of Committee Meeting The Shipping Coordinating Committee (SHC) will conduct an... Staff Regulations and Staff Rules --Accounts and audit: Final accounts for the finance period 2012 and...

  5. Coordinating Interactions: The Event Coordination Notation

    DEFF Research Database (Denmark)

    Kindler, Ekkart

    The purpose of a domain model is to concisely capture the concepts of an application’s domain, and their relation among each other. Even though the main purpose of domain models is not on implementing the application, major parts of an application can be generated from the application’s domain...... on a much more technical level. The Event Coordination Notation (ECNO) allows modelling the behaviour of an application on a high level of abstraction that is closer to the application’s domain than to the software realizing it. Still, these models contain all necessary details for actually executing...... models fully automatically with today’s technologies. The focus of today’s code generation technologies, however, is mostly on the structural aspects of the domain; the domain’s behaviour is often not modelled at all, or implemented manually based on some informal models, or the behaviour is modelled...

  6. News in wound healing and management

    DEFF Research Database (Denmark)

    Gottrup, Finn; Jørgensen, Bo; Karlsmark, Tonny

    2009-01-01

    . In the treatment of wounds, the new trend in the wound device marked is to produce dressings containing compounds or drugs. This could be local antiseptics (silver, other antiseptics, honey) and pain relieving drugs such as ibuprofen and morphine. New treatments such as anti-tumor necrosis factor alfa (anti...... is still at an exploratory level. Organizing models for optimal wound management are constantly being developed and refined. SUMMARY: Recent knowledge on the importance of new dressing materials containing active substances, new treatments for atypical wounds, influencing factors on the healing process...... and organization in the wound area are increasingly been launched. This may in the coming years significantly improve the treatment outcome of problem wounds....

  7. A current affair: electrotherapy in wound healing

    Science.gov (United States)

    Hunckler, Jerome; de Mel, Achala

    2017-01-01

    New developments in accelerating wound healing can have immense beneficial socioeconomic impact. The wound healing process is a highly orchestrated series of mechanisms where a multitude of cells and biological cascades are involved. The skin battery and current of injury mechanisms have become topics of interest for their influence in chronic wounds. Electrostimulation therapy of wounds has shown to be a promising treatment option with no-device-related adverse effects. This review presents an overview of the understanding and use of applied electrical current in various aspects of wound healing. Rapid clinical translation of the evolving understanding of biomolecular mechanisms underlying the effects of electrical simulation on wound healing would positively impact upon enhancing patient’s quality of life. PMID:28461755

  8. Chitin and chitosan: biopolymers for wound management.

    Science.gov (United States)

    Singh, Rita; Shitiz, Kirti; Singh, Antaryami

    2017-12-01

    Chitin and chitosan are biopolymers with excellent bioactive properties, such as biodegradability, non-toxicity, biocompatibility, haemostatic activity and antimicrobial activity. A wide variety of biomedical applications for chitin and chitin derivatives have been reported, including wound-healing applications. They are reported to promote rapid dermal regeneration and accelerate wound healing. A number of dressing materials based on chitin and chitosan have been developed for the treatment of wounds. Chitin and chitosan with beneficial intrinsic properties and high potential for wound healing are attractive biopolymers for wound management. This review presents an overview of properties, biomedical applications and the role of these biopolymers in wound care. © 2017 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  9. [Wound Ballistics – a Brief Overview].

    Science.gov (United States)

    Bolliger, Stephan A; Eggert, Sebastian; Thali, Michael J

    2016-02-03

    Wound ballistics examines the specific effect, namely the wound profile, of bullets on the body by firing at synthetic models made of ordnance gelatine, glycerin soap and synthetic bones, validated with real cases from (battlefield) surgery and forensic pathology. Wound profile refers to the penetration depth, the bullet deformation/ fragmentation, the diameter of the permanent and the temporary wound cavity. Knowing these features and the used ammunition a surgeon can rapidly assess the amount damage within a patient. The forensic pathologist can draw conclusions as to the used ammunition based on the wound profile. By measuring of the destructive capability of different ammunition types, wound ballistics lays the foundation for guidelines concerning the maximum effect of military ammunition.

  10. 2015: "key word" for wound care business success.

    Science.gov (United States)

    Schaum, Kathleen D

    2015-01-01

    Wound care professionals should consider all this attention to the key word documentation as your 2015 "heads-up." You should conduct a self-audit and request an external audit of your own documentation against all the regulations, LCDs, Policy Articles, newsletters, and educational programs that CMS and your MACs are providing. You should also embrace the questioning and assistance, pertaining to your documentation, which you may receive from your coders and billers. These coding and billing professionals should be your "best friends" to help you improve your clinical documentation as soon as possible. You cannot afford to be one of the professionals who are requested to repay for services you actually provided just because you did not take the time to document your excellent wound care work.

  11. Corneal wound healing is compromised by immunoproteasome deficiency.

    Directory of Open Access Journals (Sweden)

    Deborah A Ferrington

    Full Text Available Recent studies have revealed roles for immunoproteasome in regulating cell processes essential for maintaining homeostasis and in responding to stress and injury. The current study investigates how the absence of immunoproteasome affects the corneal epithelium under normal and stressed conditions by comparing corneas from wildtype (WT mice and those deficient in two immunoproteasome catalytic subunits (lmp7(-/-/mecl-1(-/-, L7M1. Immunoproteasome expression was confirmed in WT epithelial cells and in cells of the immune system that were present in the cornea. More apoptotic cells were found in both corneal explant cultures and uninjured corneas of L7M1 compared to WT mice. Following mechanical debridement, L7M1 corneas displayed delayed wound healing, including delayed re-epithelialization and re-establishment of the epithelial barrier, as well as altered inflammatory cytokine production compared to WT mice. These results suggest that immunoproteasome plays an important role in corneal homeostasis and wound healing.

  12. Spectroscopic Biomarkers for Monitoring Wound Healing and Infection in Wounds

    Science.gov (United States)

    2015-06-01

    collecting Raman spectra of wound effluent, and anticipate the completion of that task by the end of the grant cycle (September 30th, 2015...tomographic imaging of canine bone tissue. J Biomed Opt 2008; 13:020506. 69. Chrit L, Hadjur C, Morel S, Sockalingum G, Lebourdon G, Leroy F, Manfait M. In...C for 1 minute, followed by 35 cycles of96°C for 15 seconds, 60°C for 45 seconds, and 72°C for 45 seconds. Final extension at 72°C was clone for 2

  13. Keratin-based Wound Care Products for Treatment of Resistant Vascular Wounds

    OpenAIRE

    Than, Martin P.; Smith, Robert A.; Hammond, Catherine; Kelly, Robert; Marsh, Clive; Maderal, Andrea D.; Kirsner, Robert S.

    2012-01-01

    Use of new keratin-based wound dressings represent a novel approach to wound management. The authors present three patients with recalcitrant, venous and mixed venous, and arterial leg ulcers treated with these dressings. Improvement in each case was observed.

  14. [Wound information management system: a standardized scheme for acquisition, storage and management of wound information].

    Science.gov (United States)

    Liu, Hu; Su, Rong-jia; Wu, Min-jie; Zhang, Yi; Qiu, Xiang-jun; Feng, Jian-gang; Xie, Ting; Lu, Shu-liang

    2012-06-01

    To form a wound information management scheme with objectivity, standardization, and convenience by means of wound information management system. A wound information management system was set up with the acquisition terminal, the defined wound description, the data bank, and related softwares. The efficacy of this system was evaluated in clinical practice. The acquisition terminal was composed of the third generation mobile phone and the software. It was feasible to get access to the wound information, including description, image, and therapeutic plan from the data bank by mobile phone. During 4 months, a collection of a total of 232 wound treatment information was entered, and accordingly standardized data of 38 patients were formed automatically. This system can provide standardized wound information management by standardized techniques of acquisition, transmission, and storage of wound information. It can be used widely in hospitals, especially primary medical institutions. Data resource of the system makes it possible for epidemiological study with large sample size in future.

  15. Advances in Wound Healing: A Review of Current Wound Healing Products

    Directory of Open Access Journals (Sweden)

    Patrick S. Murphy

    2012-01-01

    Full Text Available Successful wound care involves optimizing patient local and systemic conditions in conjunction with an ideal wound healing environment. Many different products have been developed to influence this wound environment to provide a pathogen-free, protected, and moist area for healing to occur. Newer products are currently being used to replace or augment various substrates in the wound healing cascade. This review of the current state of the art in wound-healing products looks at the latest applications of silver in microbial prophylaxis and treatment, including issues involving resistance and side effects, the latest uses of negative pressure wound devices, advanced dressings and skin substitutes, biologic wound products including growth factor applications, and hyperbaric oxygen as an adjunct in wound healing. With the abundance of available products, the goal is to find the most appropriate modality or combination of modalities to optimize healing.

  16. Introduction to Coordination Chemistry

    CERN Document Server

    Lawrance, Geoffrey Alan

    2010-01-01

    Introduction to Coordination Chemistry examines and explains how metals and molecules that bind as ligands interact, and the consequences of this assembly process. This book describes the chemical and physical properties and behavior of the complex assemblies that form, and applications that may arise as a result of these properties. Coordination complexes are an important but often hidden part of our world?even part of us?and what they do is probed in this book. This book distills the essence of this topic for undergraduate students and for research scientists.

  17. Effect of Topical Estrogen in the Mangement of Traumatic Facial Wounds

    Directory of Open Access Journals (Sweden)

    Seyed Amirhosein Ghazizadeh Hashemi

    2016-01-01

    Full Text Available Introduction: Acute skin wound healing is a complicated process comprising various phases. Recent animal studies have shown that steroid sex hormones such as estrogen maybe helpful in the regulation of several pathophysiologic stages that are involved in wound healing. In this study we examined the effects of topical estrogen in the treatment of traumatic facial wounds.   Materials and Methods: Patients referred to Luqman Hospital, Tehran with traumatic wounds were enrolled in this case-control study into two groups of equal size. From the second week of the study, topical estrogen (0.625 mg conjugated topical estrogen ointment was administered in the case group, while the control group received a Eucerin dressing only. The two groups were then compared in terms of wound healing rate on Day 7,14, and 30.   Results: Thirty patients with mean age of 16.02+36.23 years were compared in the control and estrogen-treated groups. After treatment, no scars or keloids were observed in either group. The wound area in the estrogen group was lower than that in the control group on Day 14 and 30, but the difference was not significant (P>0.05. Healing rates in the control group on Day  14 (7.1+42.3 vs.50.3+4.9 mm2 and Day 30 (1.9+93.5 vs. + 97.3+0.6 mm2 (were lower than those in the estrogen group, but the differences were not significant (P>0.05. Findings show that the required time for wound healing in the estrogen-treated group was lower than that in the control group, but the difference was not significant (P>0.05.   Conclusion:  Based on this study, topical estrogen has no effect on the rate of wound healing or the rate of wound area .

  18. Effect of Topical Estrogen in the Mangement of Traumatic Facial Wounds

    Science.gov (United States)

    Ghazizadeh Hashemi, Seyed Amirhosein; Barati, Behrooz; Mohammadi, Hosein; Saeidi, Masumeh; Bahreini, Abbas; Kiani, Mohammad Ali

    2016-01-01

    Introduction: Acute skin wound healing is a complicated process comprising various phases. Recent animal studies have shown that steroid sex hormones such as estrogen maybe helpful in the regulation of several pathophysiologic stages that are involved in wound healing. In this study we examined the effects of topical estrogen in the treatment of traumatic facial wounds. Materials and Methods: Patients referred to Luqman Hospital, Tehran with traumatic wounds were enrolled in this case-control study into two groups of equal size. From the second week of the study, topical estrogen (0.625 mg conjugated topical estrogen ointment) was administered in the case group, while the control group received a Eucerin dressing only. The two groups were then compared in terms of wound healing rate on Day 7,14, and 30. Results: Thirty patients with mean age of 16.02+36.23 years were compared in the control and estrogen-treated groups. After treatment, no scars or keloids were observed in either group. The wound area in the estrogen group was lower than that in the control group on Day 14 and 30, but the difference was not significant (P>0.05). Healing rates in the control group on Day 14 (7.1+42.3 vs.50.3+4.9 mm2) and Day 30 (1.9+93.5 vs. + 97.3+0.6 mm2) (were lower than those in the estrogen group, but the differences were not significant (P>0.05). Findings show that the required time for wound healing in the estrogen-treated group was lower than that in the control group, but the difference was not significant (P>0.05). Conclusion: Based on this study, topical estrogen has no effect on the rate of wound healing or the rate of wound area. PMID:26878003

  19. Wound healing potentials of Thevetia peruviana: Antioxidants and inflammatory markers criteria

    Directory of Open Access Journals (Sweden)

    Nazneen Rahman

    2017-10-01

    Full Text Available Thevetia peruviana is a medicinal plant used in the treatment of external wounds, infected area, ring worms, tumours etc. in traditional system of medicine. The aim of the study was to evaluate the wound healing potentials of T. peruviana leaves hexane (LH and fruit rind (FW water extracts and to prove the folkloric claims. The antimicrobial, antioxidant and anti-inflammatory potentials could be important strategies in defining potent wound healing drug. Based on these approaches the current study was designed using incision, excision and dead space wound models with the biochemical, antioxidant enzymes and inflammatory marker analysis. The fruit rind water extract showed highest WBS of 1133 ± 111.4 g. The extracts in excision model retrieved the excised wound i.e. complete healing of wound at day 14. The hydroxyproline content of FW and LH treated dry granuloma tissue was increased to 65.73 ± 3.2 mg/g and 53.66 ± 0.38 mg/g, accompanied by elevations of hexosamine and hexauronic acid with upregulation of GSH, catalase, SOD, peroxidase and the down regulation of the inflammatory marker (NO and oxidative stress marker (LPO in wet granulation tissue was documented. Conclusively, both the extracts showed enhanced WBS, rate of wound contraction, skin collagen tissue development, and early epithelisation. Therapeutic wound healing effect was further proven by reduced free radicals and inflammatory makers associated with enhanced antioxidants and connective tissue with histological evidence of more collagen formation. The present research could establish T. peruviana as potential source of effective wound healing drugs.

  20. [The wounded body, knowledge and art symbolism].

    Science.gov (United States)

    Segura Jorda, Gloria

    2011-02-01

    A brief tour through all art periods, analyzing and searching, to determine the meaning and symbolism of the wound in each period. To study the relationship and symbolism art / body / wound, is a vast and complex task. Can be approached from every angle imaginable. Different disciplines such as anthropology history and philosophy medicine, and now the art, we have provided different interpretations about the meaning representation and wounded human body through the centuries.

  1. Wound healing properties of Artocarpus heterophyllus Lam.

    Science.gov (United States)

    Gupta, Nilesh; Jain, U K; Pathak, A K

    2009-04-01

    The studies on excision wound healing model reveals significant wound healing activity of the methanolic leaf extract (simple ointment 5%) of "Artocarpus heterophyllus" ham which is comparable with standard (Betadine). In the excision model, the period of epithelization, of the extract treated group was found to be higher than the controlgroup and slightly lesser than standard treated group of animals on the up to 16(th) post wounding day.

  2. Alternatives for animal wound model systems.

    Science.gov (United States)

    Stephens, Phil; Caley, Matthew; Peake, Matthew

    2013-01-01

    In this chapter a review of animal model systems already being utilized to study normal and pathologic wound healing is provided. We also go into details on alternatives for animal wound model systems. The case is made for limitations in the various approaches. We also discuss the benefits/limitations of in vitro/ex vivo systems bringing everything up to date with our current work on developing a cell-based reporter system for diabetic wound healing.

  3. Dermal Coverage of Traumatic War Wounds

    Science.gov (United States)

    2017-01-01

    healing/non-healing of wound and donor site • Graft loss • Heterotrophic ossification • Infection • Scar contracture • Durability (i.e. abrasions/ injuries ...AWARD NUMBER: W81XWH-13-2-0004 TITLE: "Dermal Coverage of Traumatic War Wounds ” PRINCIPAL INVESTIGATOR: Dr. Leon Nesti CONTRACTING...REPORT DATE January 2017 2. REPORT TYPE Final 3. DATES COVERED (From - To) 31 Oct 2012- 30 Oct 2016 " Dermal Coverage of Traumatic War Wounds ” 5a

  4. Results of vacuum assisted wound closure application.

    Science.gov (United States)

    Atay, Tolga; Burc, Halil; Baykal, Yakup Barbaros; Kirdemir, Vecihi

    2013-08-01

    In recent past, various methods have been used for wound treatment purpose. In this study, we aimed to compare our results established from the vacuum-assisted wound closure method, which has gained popularity day by day, with the literature. A total of 48 patients, who received vacuum-assisted wound closure treatment in our clinic between 2007and 2010, were included in this study. Etiological distribution of the patients was as follows: 32 traumatic, 6 pressure sore, 9 diabetic, and 1 iliac disarticulation. All cases were evaluated in terms of age, gender, etiology, period of treatment, and size of the wound. In the patients studied, 42 were men (87.5 %) and 6 were women (12.5 %). Mean age of the patients was 39.6 years (11-61 years). All of our traumatic patients suffered from open fracture. After the vacuum-assisted wound closure application, wound size reduced by 28.8 %, while the mean area of the surface of the wound was 94.7 cm(2) (13.7-216.3 cm(2)) on average. After the wounds became ready for surgery, 15 of them were treated with split-thickness grafting, 9 of them were treated with secondary suture, 18 of them were treated with full-thickness grafting, and 6 of them were treated with flap. Average period of the application of vacuum-assisted wound closure was 11.6 days (7-15 days). Results of vacuum-assisted wound closure can be regarded as satisfactory when cases are selected properly. This system has three different effect mechanisms. Firstly, it increases local blood flow on the wound bed. Secondly, cell proliferation is triggered following the mechanic stress. Thirdly, vacuum removes the proteases from the environment which obstructs healing. Therefore, it is intended to prepare alive wound bed which is required for subsequent soft tissue reconstructions.

  5. Bromelain ameliorates the wound microenvironment and improves the healing of firearm wounds.

    Science.gov (United States)

    Wu, Si-Yu; Hu, Wei; Zhang, Bo; Liu, Shuai; Wang, Jian-Min; Wang, Ai-Min

    2012-08-01

    In a previous study, we proposed a new therapy using topical bromelain as a supplement to simple wound-track incision for the debridement of firearm wounds. This enzymatic debridement greatly simplified the management of high-velocity gunshot wounds in a pig model, and bromelain was confirmed to improve wound healing. The purpose of the present study was to investigate the effect of bromelain on the microenvironment of firearm wounds. Sixteen Chinese landrace pigs wounded by high-velocity projectiles were divided randomly into four groups: wound incision (group I), incision + bromelain (group IB), wound excision (group E), and control. Blood perfusion, oxygen partial pressure (pO(2)), and the content of tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β in wound-track tissue were measured. Wound healing was also noted. The recovery of blood perfusion in tissue and pO(2) in wound tracks was significantly more rapid in group IB and group E than in group I and control. The tissue level of TNF-α was significantly lower in group IB than in group I and control 48 h and 72 h post-wounding, and was lower than in group E 48 h post-wounding. The tissue level of TGF-β in group IB was sustained at a significantly higher level than in the other three groups. Wound healing time was also shorter in group IB. Enzymatic debridement using topical bromelain in incised wound tracks accelerates the recovery of blood perfusion, pO(2) in wound tissue, controls the expression of TNF-α and raises the expression of TGF-β. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Topical Antimicrobial Therapy for Treating Chronic Wounds

    National Research Council Canada - National Science Library

    Benjamin A. Lipsky; Christopher Hoey

    2009-01-01

    .... Topical therapy affords many potential advantages but also has disadvantages. Opinions differ on which clinical signs define wound infection and on whether quantitative microbiological studies are useful...

  7. Practices in Wound Healing Studies of Plants

    Directory of Open Access Journals (Sweden)

    Rupesh Thakur

    2011-01-01

    Full Text Available Wounds are the result of injuries to the skin that disrupt the other soft tissue. Healing of a wound is a complex and protracted process of tissue repair and remodeling in response to injury. Various plant products have been used in treatment of wounds over the years. Wound healing herbal extracts promote blood clotting, fight infection, and accelerate the healing of wounds. Phytoconstituents derived from plants need to be identified and screened for antimicrobial activity for management of wounds. The in vitro assays are useful, quick, and relatively inexpensive. Small animals provide a multitude of model choices for various human wound conditions. The study must be conducted after obtaining approval of the Ethics Committee and according to the guidelines for care and use of animals. The prepared formulations of herbal extract can be evaluated by various physicopharmaceutical parameters. The wound healing efficacies of various herbal extracts have been evaluated in excision, incision, dead space, and burn wound models. In vitro and in vivo assays are stepping stones to well-controlled clinical trials of herbal extracts.

  8. Wound Healing in Mac-1 Deficient Mice

    Science.gov (United States)

    2017-05-01

    other studies have demonstrated that the treatment of wounds with M2 macrophages does not benefit wound healing. 15 Given the importance of... Wound healing in Mac-1 deficient mice Lin Chen, MD, PhD 1 ; Sridevi Nagaraja, PhD 2 ; Jian Zhou, BS 1 ; Yan Zhao, BS 1 ; David Fine, BS 1...Alexander Y. Mitrophanov, PhD 2 ; Jaques Reifman, PhD 2 ; Luisa A. DiPietro, DDS, PhD 1 1 Center for Wound Healing and Tissue Regeneration, College of

  9. STRESS PROLONGS WOUND HEALING POST CESAREAN SECTION

    Directory of Open Access Journals (Sweden)

    Ah. Yusuf

    2017-07-01

    Full Text Available Introduction: Decision for cesarean section may lead to the stress for women in delivery. Stress response requires longer recovery time in post cesarean section patients. Most of patients who experience stress before and after surgical is associated with wound healing delay. When this condition continues, the wound will have a higher risk of infection. The objective of this study was to analyze correlation between stress and wound healing phase in post cesarean section patients. Method: A cross sectional design was used in this study. The population were women with cesarean section, both elective or emergency, in Delivery Room I RSU Dr. Soetomo Surabaya. Samples were recruited by using purposive sampling, with 28 samples who met to the inclusion criterias. The observed variables were stress and wound healing phase in post cesarean section patient. Stress data were collected by interview and wound healing measurement done by observation on the 3rd day post cesarean section. Result: The result showed that women with stress experience wound healing delay. The characteristic of wound healing delay was prolonged on inflammation phase, nevertheless there was presence of granulation tissue. Spearman’s rho correlation showed that correlation value r=0.675 with p=0.000. Discussion: It can be concluded that there was strong significant correlation between stress and wound healing phase in post cesarean section patients. It is important to give this information to the patients with cesarean section in order to prevent stress and delay in wound healing phase.

  10. Shock wave therapy in wound healing.

    Science.gov (United States)

    Qureshi, Ali A; Ross, Kimberly M; Ogawa, Rei; Orgill, Dennis P

    2011-12-01

    Recently, shock wave therapy has been investigated as an adjuvant therapy in the treatment of acute and chronic wounds. There are several devices with focused and unfocused shock waves that have been administered to a heterogenous group of wounds. Encouraging preclinical and clinical studies suggest that shock wave therapy may promote wound healing with little or no adverse events, prompting investigations into the mechanism of action and additional clinical trials. The peer-reviewed literature within the past 10 years was studied using an evidence-based approach. Preclinical studies demonstrate that shock wave therapy affects cellular function and leads to the expression of several genes and elaboration of growth factors known to promote wound healing. Limited clinical trials are encouraging for the use of shock wave therapy in the treatment of acute and chronic wounds. Serious complications, including wound infections, bleeding, hematomas, seromas, and petechiae, have not been reported in the largest of these studies. Shock wave therapy is an intriguing physical modality that may play an important role as an adjuvant therapy in wound healing. To date, there is no consensus on which wounds are most likely to benefit from shock wave therapy and what the optimal power, degree of focus, and frequency or number of cycles should be. Well-designed preclinical and clinical studies are necessary to better understand shock wave therapy in wound healing.

  11. A current affair: electrotherapy in wound healing

    Directory of Open Access Journals (Sweden)

    Hunckler J

    2017-04-01

    Full Text Available Jerome Hunckler, Achala de Mel UCL Division of Surgery and Interventional Sciences, Faculty of Medical Sciences, University College London, London, UK Abstract: New developments in accelerating wound healing can have immense beneficial socioeconomic impact. The wound healing process is a highly orchestrated series of mechanisms where a multitude of cells and biological cascades are involved. The skin battery and current of injury mechanisms have become topics of interest for their influence in chronic wounds. Electrostimulation therapy of wounds has shown to be a promising treatment option with no-device-related adverse effects. This review presents an overview of the understanding and use of applied electrical current in various aspects of wound healing. Rapid clinical translation of the evolving understanding of biomolecular mechanisms underlying the effects of electrical simulation on wound healing would positively impact upon enhancing patient’s quality of life. Keywords: electrotherapy, wound healing, infection, bioelectric current, exogenous current, bioelectric medicine, electrical stimulation, chronic wound, acute wound

  12. Principles of management of shotgun wounds.

    Science.gov (United States)

    Walker, M L; Poindexter, J M; Stovall, I

    1990-02-01

    As an instrument of close range combat, the shotgun has no parallel. At short distances, its destructive capacity parallels that seen from high velocity missile injury. In this study, the history of the shotgun, wound ballistics, principles of initial therapy and special management problems related to shotgun wounds of specific sites are reviewed. An analysis of pooled data on abdominal shotgun wounds is presented. A subset of patients who do not require abdominal exploration exists. Specific problems encountered in defining this subset are enumerated. Three algorithms are presented that summarize our current management approach to shotgun wounds of the torso and extremities.

  13. A CLINICAL STUDY OF ABDOMINAL WOUND DEHISCENCE

    Directory of Open Access Journals (Sweden)

    Zahir Hussain

    2016-10-01

    Full Text Available BACKGROUND Abdominal wound dehiscence is a preventable complication, but is still seen. When present, it poses problem in the management of the case, increases the morbidity and mortality of the patient. The present study is a prospective study done from January 2010-May 2016 with an objective to find out the incidence of wound dehiscence, the most common pathologies associated with dehiscence and to find out the statistical significance of the difference risk factors causing wound dehiscence and to evaluate the role of tension sutures in prevention of wound dehiscence. MATERIALS AND METHODS 291 major laparotomies were followed from January 2010-September 2016. There were 21 cases of dehiscence and from the remaining 270 cases, 58 patients were chosen as controls who underwent the same procedure, but without dehiscence. 15 factors were analysed and compared between the dehiscence and control groups. RESULTS The incidence was found to be 7.2%. Peritonitis was the most common pathology. The significant factors were age more than 50, wound infection. Tension suture application has shown to reduce the incidence of wound dehiscence. CONCLUSIONS  Intra-abdominal sepsis (peritonitis increases the incidence of wound dehiscence.  Age >50, Uraemic, Jaundiced, Obesity, Malnutrition increases the incidence of wound dehiscence.  Wound infection was a highly significant factor having 8 times more risk of dehiscence.

  14. Astroglial networks promote neuronal coordination.

    Science.gov (United States)

    Chever, Oana; Dossi, Elena; Pannasch, Ulrike; Derangeon, Mickael; Rouach, Nathalie

    2016-01-12

    Astrocytes interact with neurons to regulate network activity. Although the gap junction subunits connexin 30 and connexin 43 mediate the formation of extensive astroglial networks that cover large functional neuronal territories, their role in neuronal synchronization remains unknown. Using connexin 30- and connexin 43-deficient mice, we showed that astroglial networks promoted sustained population bursts in hippocampal slices by setting the basal active state of neurons. Astroglial networks limited excessive neuronal depolarization induced by spontaneous synaptic activity, increased neuronal release probability, and favored the recruitment of neurons during bursting, thus promoting the coordinated activation of neuronal networks. In vivo, this sustained neuronal coordination translated into increased severity of acutely evoked epileptiform events and convulsive behavior. These results revealed that connexin-mediated astroglial networks synchronize bursting of neuronal assemblies, which can exacerbate pathological network activity and associated behavior. Our data thus provide molecular and biophysical evidence predicting selective astroglial gap junction inhibitors as anticonvulsive drugs. Copyright © 2016, American Association for the Advancement of Science.

  15. Honey and wound dehiscence: A study of surgical wounds in the ...

    African Journals Online (AJOL)

    2014-08-20

    Aug 20, 2014 ... The smaller the initial circumference of the surgical wound, the shorter the duration of healing and this was significant (P = 0.001) in .... initial circumference of the wound and duration of clinical healing of the surgical wounds after .... for the “respiratory burst” in macrophages which is an important part of their ...

  16. Expedited wound healing with noncontact, low-frequency ultrasound therapy in chronic wounds: a retrospective analysis.

    Science.gov (United States)

    Kavros, Steven J; Liedl, David A; Boon, Andrea J; Miller, Jenny L; Hobbs, Julie A; Andrews, Karen L

    2008-09-01

    To evaluate the clinical role of noncontact, low-frequency ultrasound therapy (MIST Therapy System; Celleration, Eden Prairie, Minnesota) in the treatment of chronic lower-extremity wounds. A retrospective observational study. A multidisciplinary, vascular wound-healing clinic. One hundred sixty-three patients who received MIST Therapy plus standard of care (treatment group) and 47 patients who received the standard of care alone (control group). All wounds in the control and treatment groups received the standard of wound care and were followed for 6 months. In the treatment group, MIST Therapy was administered to wounds 3 times per week for 90 days or until healed. Proportion of wounds healed and wound volume reduction. Rate of healing was also quantified using 1-way analysis of variance to determine the slope of the regression line from starting volume to ending volume, where a steeper slope indicates a faster healing rate. Outcomes were evaluated in all wounds and etiology-specific subgroups. A significantly greater percentage of wounds treated with MIST Therapy and standard of care healed as compared with those treated with the standard of care alone (53% vs 32%; P = 0.009). The slope of the regression line in the MIST arm (1.4) was steeper than the slope in the control arm (0.22; P = .002), indicating a faster rate of healing in the MIST-treated wounds. The rate of healing and complete closure of chronic wounds in patients improved significantly when MIST Therapy was combined with standard wound care.

  17. ENDOSURGICAL TECHNOLOGY FOR CHEST WOUNDS

    Directory of Open Access Journals (Sweden)

    O. V. Voskresensky

    2016-01-01

    Full Text Available BACKGROUND Penetrating chest injuries are a common cause of hospitalization for young patients.Various types of thoracotomy prevails over the other surgical approaches performed both under absolute and relative indications, depending on the location of wounds.PURPOSE To analyze the tactics and evaluate the possibility of thoracoscopy in order to reduce the number of unreasonable thoracotomies and reduce trauma due to surgical intervention.MATERIAL AND METHODS We studied 596 medical histories of victims who had been operated in 2002–2012. Thoracoscopy was performed in 236 patients, traditional tactics was applied in 360 victims. Wounds in the diaphragmatic area of the chest were in 210 victims, in the “heart” area — in 172 patients, in the intersection of these two zones — 44 cases, in the projection of the lung peripheral part — 49 cases and paravertebral area of the chest — in 52 patients. Typical thoracotomy (TT was performed in 27% of cases, atypical thoracotomy (AT — 42.5%, and drainage of the pleural space (DPS — 30.3% of cases.RESULT Thoracoscopy (TS could be carried out in 42.2% of patients who had undergone TT, and in 79.4% of patients who had undergone AT. Overall performance of the TS was possible in 70% of patients with penetrating chest wounds (PCW. Absolute contraindications for TS occurred in 29.1% of the victims.

  18. Polymeric coordination compounds

    Indian Academy of Sciences (India)

    Administrator

    Metal coordination polymers with one- and two-dimensional structures are of current interest due to their possible relevance to material science 1. In continuation of our previous studies 2,3, several new polymeric compounds are reported here. Among the complexes of silver with aminomethyl pyridine (amp) ...

  19. Coordination Games on Graphs

    NARCIS (Netherlands)

    K.R. Apt (Krzysztof); M.M. Rahn (Mona); G. Schäfer (Guido); S.E. Simon (Sunil)

    2014-01-01

    htmlabstractWe introduce natural strategic games on graphs, which capture the idea of coordination in a local setting.We show that these games have an exact potential and have strong equilibria when the graph is a pseudoforest. We also exhibit some other classes of games for which a strong

  20. Coordination Compounds in Biology

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 4; Issue 6. Coordination Compounds in Biology - The Chemistry of Vitamin B12 and Model Compounds. K Hussian Reddy. General Article Volume 4 Issue 6 June 1999 pp 67-77 ...

  1. Recursive Advice for Coordination

    DEFF Research Database (Denmark)

    Terepeta, Michal Tomasz; Nielson, Hanne Riis; Nielson, Flemming

    2012-01-01

    Aspect-oriented programming is a programming paradigm that is often praised for the ability to create modular software and separate cross-cutting concerns. Recently aspects have been also considered in the context of coordination languages, offering similar advantages. However, introducing aspects...

  2. Coordination Games on Graphs

    NARCIS (Netherlands)

    Apt, K.R.; Rahn, M.; Schäfer, G.; Simon, S.; Liu, T.-Y.; Qi, Q.; Ye, Y.

    2014-01-01

    We introduce natural strategic games on graphs, which capture the idea of coordination in a local setting. We show that these games have an exact potential and have strong equilibria when the graph is a pseudoforest. We also exhibit some other classes of graphs for which a strong equilibrium exists.

  3. Coordinating Supplemental Reading Instruction

    Science.gov (United States)

    Deeney, Theresa A.

    2008-01-01

    Although supplemental reading services are meant to improve reading achievement of struggling readers and students with reading disabilities, without concerted effort to ensure communication and coordination with in-school instruction, they may fall short of their desired mark. To promote learning, it is critical that any services provided outside…

  4. Expression of transforming growth factor beta(1), beta(3), and basic fibroblast growth factor in full-thickness skin wounds of equine limbs and thorax.

    Science.gov (United States)

    Theoret, C L; Barber, S M; Moyana, T N; Gordon, J R

    2001-01-01

    To map the expression of transforming growth factor (TGF)-beta(1), TGF-beta(3), and basic fibroblast growth factor (bFGF) in full-thickness skin wounds of the horse. To determine whether their expression differs between limbs and thorax, to understand the pathogenesis of exuberant granulation tissue. Six wounds were created on one lateral metacarpal area and one midthoracic area of each horse. Sequential wound biopsies allowed comparison of the temporal expression of growth factors between limb and thoracic wounds. Four 2- to 4-year-old horses. Wounds were assessed grossly and histologically at 12 and 24 hours, and 2, 5, 10, and 14 days postoperatively. ELISAs were used to measure the growth factor concentrations of homogenates of wound biopsies taken at the same timepoints. TGF-beta(1) peaked at 24 hours in both locations and returned to baseline in thoracic wounds by 14 days but remained elevated in limb wounds for the duration of the study. Expression kinetics of TGF-beta(3) differed from those of TGF-beta(1). TGF-beta(3) concentrations gradually increased over time, showing a trend toward an earlier and higher peak in thoracic compared with limb wounds. bFGF expression kinetics resembled those of TGF-beta(1), but no statistically significant differences existed between limb and thoracic wounds. Growth factor expression is up-regulated during normal equine wound repair. TGF-beta(1) and TGF-beta(3) show a reciprocal temporal regulation. Statistically significant differences exist between limb and thoracic wounds with respect to TGF-beta(1) expression. The persistence of TGF-beta(1) expression in leg wounds may be related to the development of exuberant granulation tissue in this location, because TGF-beta(1) is profibrotic. Copyright 2001 by The American College of Veterinary Surgeons

  5. Extremely low frequency electromagnetic field and wound healing: implication of cytokines as biological mediators.

    Science.gov (United States)

    Pesce, Mirko; Patruno, Antonia; Speranza, Lorenza; Reale, Marcella

    2013-03-01

    Wound healing is a highly coordinated and complex process involving various cell types, chemical mediators and the surrounding extracellular matrix, resulting in a tightly orchestrated re-establishment of tissue integrity by specific cytokines. It consists of various dynamic processes including a series of overlapping phases: inflammation, proliferation, re-epithelialization and remodeling. One of the underlying mechanisms responsible for the disturbances in wound healing is an out-of-control inflammatory response that can cause pathological consequences, such as hypertrophic scars, keloids or chronic wounds and ulcers. Recently, several reports have evaluated the effects of extremely low frequency electromagnetic fields (EMFs) on tissue repair. In particular, the data analysis supports an anti-inflammatory effect of EMFs by the modulation of cytokine profiles that drive the transition from a chronic pro-inflammatory state to an anti-inflammatory state of the healing process. In this review, we focus on the effect of EMFs on skin wound healing showing emerging details of the anti-inflammatory effects of EMFs, with a view to cytokines as candidate biomarkers. Molecular clarification of the mechanisms involved in the modulation of inflammatory factors following exposure to EMFs will provide a better understanding of the cellular responses induced by EMFs and a potential, additional treatment in non-responding, chronic wounds.

  6. What is Coordinated in Bimanual Coordination?

    Science.gov (United States)

    Mechsner, Franz; Prinz, Wolfgang

    In periodic bimanual movements there is a characteristic spontaneous tendency towards mirror-symmetry. This phenomenon has widely been interpreted as a tendency towards co-activation of homologous muscles, possibly originating in motoric neuronal structures. The experiments reported here provide evidence contrary to this common claim. The symmetry tendency in bimanual abductive/adductive finger oscillation as well as in bimanual multi-finger tapping is actually towards spatial, perceptual symmetry, without regard to the muscles and thus to the motor commands involved. It is hypothesized that, as a rule, spontaneous coordination phenomena of this kind are purely perceptual-cognitive in nature. Moreover, in the case of a bimanual circling paradigm, the reported findings reveal that highly complex, even 'impossible' movements can easily be performed if, rather than the bodily movements themselves, simple sensory consequences are controlled. It is suggested that voluntary movements are organized by representing and controlling their perceptual goals or anticipated effects, whereas the corresponding motor activity of sometimes high formal complexity is rather spontaneously and flexibly tuned in service of these effects.

  7. Coordinated Voltage Control of Active Distribution Network

    Directory of Open Access Journals (Sweden)

    Xie Jiang

    2016-01-01

    Full Text Available This paper presents a centralized coordinated voltage control method for active distribution network to solve off-limit problem of voltage after incorporation of distributed generation (DG. The proposed method consists of two parts, it coordinated primal-dual interior point method-based voltage regulation schemes of DG reactive powers and capacitors with centralized on-load tap changer (OLTC controlling method which utilizes system’s maximum and minimum voltages, to improve the qualified rate of voltage and reduce the operation numbers of OLTC. The proposed coordination has considered the cost of capacitors. The method is tested using a radial edited IEEE-33 nodes distribution network which is modelled using MATLAB.

  8. Short-term treatment of equine wounds with orf virus IL-10 and VEGF-E dampens inflammation and promotes repair processes without accelerating closure.

    Science.gov (United States)

    Bodaan, Christa J; Wise, Lyn M; Wakelin, Kirsty A; Stuart, Gabriella S; Real, Nicola C; Mercer, Andrew A; Riley, Christopher B; Theoret, Christine

    2016-11-01

    Healing is delayed in limb wounds relative to body wounds of horses, partly because of sustained inflammation and inefficient angiogenesis. In laboratory animals, proteins derived from orf virus modulate these processes and enhance healing. We aimed to compare immune cell trafficking and the inflammatory, vascular, and epidermal responses in body and limb wounds of horses and then to investigate the impact of orf virus interleukin-10 and vascular endothelial growth factor-E on these processes. Standardized excisional wounds were created on the body and forelimb of horses and their progression monitored macroscopically until healed. Tissue samples were harvested to measure the expression of genes regulating inflammation and repair (quantitative polymerase chain reaction) and to observe epithelialization (histology), innate immune cell infiltration, and angiogenesis (immunofluorescence). Delayed healing of limb wounds was characterized by intensified and extended pro-inflammatory signaling and exacerbated innate immune response, concomitant with the absence of anti-inflammatory eIL-10. Blood vessels were initially more permeable and then matured belatedly, concomitant with retarded production of angiogenic factors. Epithelial coverage was achieved belatedly in limb wounds. Viral proteins were administered to wounds of one body and one limb site/horse at days 1-3, while wounds at matching sites served as controls. Treatment dampened pro-inflammatory gene expression and the innate immune response in all wounds. It also improved angiogenic gene expression, but primarily in body wounds, where it altered blood vessel density and myofibroblast persistence. Moreover, the viral proteins increased epithelialization of all wounds. The short-term viral protein therapy did not, however, improve the healing rate of wounds in either location, likely due to suboptimal dosing. In conclusion, we have further detailed the processes contributing to protracted healing in limb wounds of

  9. Bi-Layer Wound Dressing System for Combat Casualty Care

    National Research Council Canada - National Science Library

    Martineau, Lucie; Shek, Pang N

    2004-01-01

    .... Biopsies taken from full-thickness, pig wounds infected with Ps. aeruginosa and Staph. epidermidis showed a 2- to 5-log reduction in the bacterial load of antiseptic-treated wounds compared to those of control wounds...

  10. Critical Review of Noninvasive Optical Technologies for Wound Imaging

    OpenAIRE

    Jayachandran, Maanasa; Rodriguez, Suset; Solis, Elizabeth; Lei, Jiali; Godavarty, Anuradha

    2016-01-01

    Significance: Noninvasive imaging approaches can provide greater information about a wound than visual inspection during the wound healing and treatment process. This review article focuses on various optical imaging techniques developed to image different wound types (more specifically ulcers).

  11. Equine ANXA2 and MMP1 expression analyses in an experimental model of normal and pathological wound repair.

    Science.gov (United States)

    Miragliotta, Vincenzo; Lefebvre-Lavoie, Josiane; Lussier, Jacques G; Theoret, Christine L

    2008-08-01

    Wounds on horse limbs can develop exuberant granulation tissue which resembles the human keloid. Clues gained from the study of over-scarring in horses might help control fibro-proliferative disorders. The aim of the present study was to clone full-length equine ANXA2 cDNA then to study spatio-temporal expression of ANXA2 and MMP1 mRNA and protein, potential contributors to remodeling, during repair of body (normal) and limb (fibro-proliferative) wounds in an established horse wound model. Cloning of ANXA2 was achieved by screening size-selected cDNA libraries. Expression was studied in intact skin and in biopsies of 1, 2, 3, 4 and 6-week-old wounds of the body and limb. Temporal gene expression was determined by semi-quantitative RT-PCR while protein expression was mapped immunohistochemically. ANXA2 mRNA was up-regulated only in body wounds, corroborating the superior and prompt tissue turnover at this location. Immunohistochemistry partially substantiated the mRNA data in that increased staining for ANXA2 protein was detected in neo-epidermis which formed more rapidly and completely in body wounds. MMP1 mRNA levels in body wounds significantly surpassed those of limb wounds in week one biopsies. The protein was abundant in migrating epithelium of limb wounds at weeks two and four; conversely, body wounds in which epithelialization was near complete showed diminished staining of MMP1. We conclude that ANXA2 and MMP1 might participate in remodeling during wound healing in the horse, and that differences in expression may contribute to the excessive proliferative response seen in the limb.

  12. Abdominal wound closure: current perspectives

    Directory of Open Access Journals (Sweden)

    Williams ZF

    2015-12-01

    Full Text Available Zachary F Williams, William W Hope Department of Surgery, South East Area Health Education Center, New Hanover Regional Medical Center, Wilmington, NC, USA Abstract: This review examines both early and late wound complications following laparotomy closure, with particular emphasis on technical aspects that reduce hernia formation. Abdominal fascial closure is an area of considerable variation within the field of general surgery. The formation of hernias following abdominal wall incisions continues to be a challenging problem. Ventral hernia repairs are among the most common surgeries performed by general surgeons, and despite many technical advances in the field, incisional hernia rates remain high. Much attention and research has been directed to the surgical management of hernias. Less focus has been placed on prevention of hernia formation despite its obvious importance. This review examines the effects of factors such as the type of incision, suture type and size, closure method, patient risk factors, and the use of prophylactic mesh. Keywords: incisional, abdominal, hernia, prevention, wound closure techniques 

  13. What wound up the Universe

    Energy Technology Data Exchange (ETDEWEB)

    Davies, P.

    1987-01-01

    One general property of physical systems is the irreversible rise of disorder. This fact is formalised in terms of entropy with the second law of thermodynamics, which states that in a closed system entropy never decreases. The consequences on a cosmic scale are illustrated by reference to Thomas the Tank engine being wound up and stopping when the energy is used up. In the cosmic analogy, what wound up the universe. If it was simply created and has been unwinding ever since, what evidence is there for entropy of the primeval cosmos. Three pieces of evidence are given in support of the Big Bang hypothesis. Expansion is an important aspect of the unwinding mechanism with the nature of the microwave background (the spectrum of which has a black-body form) being the most relevant fact to support this. The attempts to explain the driving force behind the Big Bang are reviewed. Strong and weak forces and the grand unified theories and antigravity are explained. The Higgs field, an excited state which can give rise to antigravity, could have driven the Universe at birth with a huge repulsive force for a brief moment sending it into a runaway expansion. This would mean that antigravity was responsible for winding up the Universe. (U.K.).

  14. Mucopolysaccharides from psyllium involved in wound healing

    NARCIS (Netherlands)

    Westerhof, W.; Das, P. K.; Middelkoop, E.; Verschoor, J.; Storey, L.; Regnier, C.

    2001-01-01

    Mucopolysaccharides derived from the husk of psyllium (Plantago ovata) have properties beneficial for wound cleansing and wound healing. Recent studies indicate that these mucopolysaccharides also limit scar formation. Our in vitro and in vivo studies aimed to investigate the mechanisms involved,

  15. December 2004 - 38 War Wounds with Fractures

    African Journals Online (AJOL)

    user

    2004-12-02

    Dec 2, 2004 ... Historically, on a conventional battlefield, about 70% of the wounded present injuries to the limbs, the remaining 30% have central wounds involving head, chest or abdomen. The longer the delay in transport to hospital facilities, especially with inadequate first aid, the higher the death rate in the central ...

  16. Antimicrobial, Wound Healing And Antioxidant Activities Of ...

    African Journals Online (AJOL)

    claims of the plant in skin diseases, wound healing activity was studied, besides antioxidant activity to understand the mechanism of wound healing. The alchoholic and aqueous extract of this plant showed significant antibacterial and antifungal activity against almost all the organisms: Micrococcus luteus, Bacillus subtilis, ...

  17. Biomechanics and Wound Healing in the Cornea

    OpenAIRE

    Dupps, William J.; Wilson, Steven E.

    2006-01-01

    The biomechanical and wound healing properties of the cornea undermine the predictability and stability of refractive surgery and contribute to discrepancies between attempted and achieved visual outcomes after LASIK, surface ablation and other keratorefractive procedures. Furthermore, patients predisposed to biomechanical failure or abnormal wound healing can experience serious complications such as keratectasia or clinically significant corneal haze, and more effective means for the identif...

  18. Status of wound management in Korea.

    Science.gov (United States)

    Namgoong, Sik; Han, Seung-Kyu

    2017-08-30

    In spite of a period of intense economic, social, and political hardship following the Korean War, the Republic of Korea has made great strides in economic growth over the past half century, and also remarkable progress in the medical field. However, wound research has been slow to take off in South Korea. Meanwhile, as is the case in many countries in Western Europe and North America, South Korea is seeing a steady increase in its aged population. The growth in the geriatric population has in turn brought on more cases of chronic wounds. Though South Korea only began to recognize the importance of wound management in the early 2000s, it was fortunate enough to have sophisticated related industries, such as biotechnology and information technology, and brilliant, industrious, and eager wound researchers, contributing to rapid development of the field. The country has particular strengths in research for innovative cell-based treatments and products for managing wounds. Notwithstanding government policy ill-equipped to sufficiently support such advancement, better communication between experts and public officials will no doubt bring forth even more achievements in this very promising field. It is in this context that this article aims to summarize current wound management practices, research, training, product development, and government policies regarding wound management in South Korea as of the year 2017. © 2017 by the Wound Healing Society.

  19. [Skillful care for chronic vascular wounds].

    Science.gov (United States)

    Goullet de Rugy, C; Lazareth, I; You, C; Stansal, A; Priollet, P

    2016-09-01

    In vascular medicine, wound care requires pluridisciplinary expertise and nursing skill. Care must be perfectly adapted to each individual patient, the specificities of each particular wound, and the underlying vascular disease. The goal is to achieve wound healing. Inappropriate care can retard healing or even aggravate the wound. The skin should be cleaned with water a non-allergic detergent and should concern the entire limb in addition to the wound itself. Fibrin or necrosis detersion is an important step that can be painful. Different tools are available. The skin around the wound should be hydrated and protected, focusing on fragile areas, such as the tibial crest and heals, in order to prevent the development of new wounds. Other more complex interventions include tenosynovectomy, bone gouging and reduction of the necrotic toe that when properly performed can prevent a new passage in the operating room. If the ischemia becomes critical, the foot should be held warm with a carded cotton, taking care to separate the toes with dry dressings in order to preserve the healthy tissue and avoid induced wounds. Finally, compression bands are indispensable in cases with edema or venous hyperpressure. A skillful banding technique is essential, especially for legs with complex morphology. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  20. Soft Tissue Wounds and Principles of Healing

    Science.gov (United States)

    2007-01-01

    carbon dioxide and waste products. The adhesion of platelets to the denuded subendothelial matrix is the hallmark of the acute phase providing an...antiseptics such as vinegar and wine in preparation for delayed primary or secondary closure [20]. Despite much being known about wounds and wound care

  1. Topical silver for treating infected wounds

    NARCIS (Netherlands)

    Vermeulen, H.; van Hattem, J. M.; Storm-Versloot, M. N.; Ubbink, D. T.

    2007-01-01

    BACKGROUND: Topical silver treatments and silver dressings are increasingly used for the local treatment of contaminated or infected wounds, however, there is a lack of clarity regarding the evidence for their effectiveness. OBJECTIVES: To evaluate the effects on wound healing of topical silver and

  2. Topical negative pressure for treating chronic wounds

    NARCIS (Netherlands)

    Ubbink, Dirk T.; Westerbos, Stijn Joël; Evans, Debra; Land, Lucy; Vermeulen, Hester

    2008-01-01

    BACKGROUND: Chronic wounds mainly affect the elderly and those with multiple health problems. Despite the use of modern dressings, some of these wounds take a long time to heal, fail to heal, or recur, causing significant pain and discomfort to the person and cost to health services. Topical

  3. Categorizing Wounds to Improve Clinical Management and ...

    African Journals Online (AJOL)

    Trauma and surgeries are common causes of wounds that require proper management to prevent complications, economic losses, pain and suffering, death or euthanasia of the affected animals. A retrospective study of 243 wounds in cattle, sheep and goats treated between 1981 and 2006 is described. It describes ...

  4. NEGATIVE PRESSURE WOUND THERAPY (NPWT) FOR THE ...

    African Journals Online (AJOL)

    OF LAPAROSTOMY WOUNDS: CASE SERIES. J. O. GISORE AND S. O. KHAINGA. SUMMARY. Laparostomy or the open abdomen can be a lifesaving intervention in surgical emergencies for abdominal compartment syndrome, wound dehiscence, trauma and intra-abdominal sepsis. However, the open abdomen imposes ...

  5. Low level diode laser accelerates wound healing.

    Science.gov (United States)

    Dawood, Munqith S; Salman, Saif Dawood

    2013-05-01

    The effect of wound illumination time by pulsed diode laser on the wound healing process was studied in this paper. For this purpose, the original electronic drive circuit of a 650-nm wavelength CW diode laser was reconstructed to give pulsed output laser of 50 % duty cycle and 1 MHz pulse repetition frequency. Twenty male mice, 3 months old were used to follow up the laser photobiostimulation effect on the wound healing progress. They were subdivided into two groups and then the wounds were made on the bilateral back sides of each mouse. Two sessions of pulsed laser therapy were carried along 15 days. Each mice group wounds were illuminated by this pulsed laser for 12 or 18 min per session during these 12 days. The results of this study were compared with the results of our previous wound healing therapy study by using the same type of laser. The mice wounds in that study received only 5 min of illumination time therapy in the first and second days of healing process. In this study, we found that the wounds, which were illuminated for 12 min/session healed in about 3 days earlier than those which were illuminated for 18 min/session. Both of them were healed earlier in about 10-11 days than the control group did.

  6. Histomorphological evaluation of wound healing - Comparison ...

    African Journals Online (AJOL)

    Vernonia amygdalina leaf juice, similar to honey, enhanced fibroblasts recruitment, epithelia cells migration, neovascularization and reduced polymorphonuclear leukocytes (PMNL) infiltration as compared to the NC at the early phase of wound healing (days 3 and 5). Vernonia amygdalina might enhance cutaneous wound ...

  7. Multiple bacterial species reside in chronic wounds

    DEFF Research Database (Denmark)

    Gjødsbøl, Kristine; Christensen, Jens Jørgen; Karlsmark, Tonny

    2006-01-01

    . aeruginosa were found to be significantly larger than ulcers without the presence of P. aeruginosa (P wound is colonised by multiple bacterial species and that once they are established many of them persist in the wound. Our results suggest that the presence...

  8. Stimulation Of Wound Healing By Lasers

    Science.gov (United States)

    Lyons, Richard F.; Abergel, R. Patrick; Lam, Thomas s.; White, Rodney A.; Dwyer, Richard M.; Uitto, Jouni

    1986-08-01

    Clinical observations have suggested that low energy lasers might stimulate wound healing. To understand the mechanism of the biostimulation, we have previously examined the effects of low energy lasers on collagen production by human skin fibroblasts and reported an increase of collagen synthesis in vitro (J. Am. Acad. Derm. 11:1142-1150, 1980. To examine the effects of low energy lasers in vivo, hairless mice were experimentally wounded, sutured and subjected to laser irradiation by He-Ne laser with a power output of 1.56 mW, and an energy fluence of 1.22 J/cm2. Experimental wounds were subjected to laser treatment every other day, for a total duration of 2 months; control wounds remained untreated. Specimens from the wounds were then examined for histology, tensile strength and total collagen content. Results demonstrated a considerable improvement of the tensile strength of the laser-irradiated wounds at 1 and 2 weeks. Furthermore, the total collagen content was significantly increased at 2 months when compared to control wounds. These results suggest a beneficial effect of He-Ne laser on wound healing in vivo.

  9. Wound healing and infection in surgery

    DEFF Research Database (Denmark)

    Sørensen, Lars Tue

    2012-01-01

    : The aim was to clarify how smoking and nicotine affects wound healing processes and to establish if smoking cessation and nicotine replacement therapy reverse the mechanisms involved.......: The aim was to clarify how smoking and nicotine affects wound healing processes and to establish if smoking cessation and nicotine replacement therapy reverse the mechanisms involved....

  10. Effect of chitosan acetate bandage on wound healing in infected and noninfected wounds in mice

    Science.gov (United States)

    Burkatovskaya, Marina; Castano, Ana P.; Demidova-Rice, Tatiana N.; Tegos, George P.; Hamblin, Michael R.

    2010-01-01

    HemCon® bandage is an engineered chitosan acetate preparation designed as a hemostatic dressing, and is under investigation as a topical antimicrobial dressing. We studied its effects on healing of excisional wounds that were or were not infected with Staphylococcus aureus, in normal mice or mice previously pretreated with cyclophosphamide (CY). CY significantly suppressed wound healing in both the early and later stages, while S. aureus alone significantly stimulated wound healing in the early stages by preventing the initial wound expansion. CY plus S. aureus showed an advantage in early stages by preventing expansion, but a significant slowing of wound healing in later stages. In order to study the conflicting clamping and stimulating effects of chitosan acetate bandage on normal wounds, we removed the bandage from wounds at times after application ranging from 1 hour to 9 days. Three days application gave the earliest wound closure, and all application times gave a faster healing slope after removal compared with control wounds. Chitosan acetate bandage reduced the number of inflammatory cells in the wound at days 2 and 4, and had an overall beneficial effect on wound healing especially during the early period where its antimicrobial effect is most important. PMID:18471261

  11. Regenerative Skin Wound Healing in Mammals: State-of-the-Art on Growth Factor and Stem Cell Based Treatments

    Directory of Open Access Journals (Sweden)

    Bizunesh M. Borena

    2015-04-01

    Full Text Available Mammal skin has a crucial function in several life-preserving processes such as hydration, protection against chemicals and pathogens, initialization of vitamin D synthesis, excretion and heat regulation. Severe damage of the skin may therefore be life-threatening. Skin wound repair is a multiphased, yet well-orchestrated process including the interaction of various cell types, growth factors and cytokines aiming at closure of the skin and preferably resulting in tissue repair. Regardless various therapeutic modalities targeting at enhancing wound healing, the development of novel approaches for this pathology remains a clinical challenge. The time-consuming conservative wound management is mainly restricted to wound repair rather than restitution of the tissue integrity (the so-called “restitutio ad integrum”. Therefore, there is a continued search towards more efficacious wound therapies to reduce health care burden, provide patients with long-term relief and ultimately scarless wound healing. Recent in vivo and in vitro studies on the use of skin wound regenerative therapies provide encouraging results, but more protracted studies will have to determine whether the effect of observed effects are clinically significant and whether regeneration rather than repair can be achieved. For all the aforementioned reasons, this article reviews the emerging field of regenerative skin wound healing in mammals with particular emphasis on growth factor- and stem cell-based therapies.

  12. Regenerative Skin Wound Healing in Mammals: State-of-the-Art on Growth Factor and Stem Cell Based Treatments.

    Science.gov (United States)

    Borena, Bizunesh M; Martens, Ann; Broeckx, Sarah Y; Meyer, Evelyne; Chiers, Koen; Duchateau, Luc; Spaas, Jan H

    2015-01-01

    Mammal skin has a crucial function in several life-preserving processes such as hydration, protection against chemicals and pathogens, initialization of vitamin D synthesis, excretion and heat regulation. Severe damage of the skin may therefore be life-threatening. Skin wound repair is a multiphased, yet well-orchestrated process including the interaction of various cell types, growth factors and cytokines aiming at closure of the skin and preferably resulting in tissue repair. Regardless various therapeutic modalities targeting at enhancing wound healing, the development of novel approaches for this pathology remains a clinical challenge. The time-consuming conservative wound management is mainly restricted to wound repair rather than restitution of the tissue integrity (the so-called "restitutio ad integrum"). Therefore, there is a continued search towards more efficacious wound therapies to reduce health care burden, provide patients with long-term relief and ultimately scarless wound healing. Recent in vivo and in vitro studies on the use of skin wound regenerative therapies provide encouraging results, but more protracted studies will have to determine whether the effect of observed effects are clinically significant and whether regeneration rather than repair can be achieved. For all the aforementioned reasons, this article reviews the emerging field of regenerative skin wound healing in mammals with particular emphasis on growth factor- and stem cell-based therapies.

  13. Coordinating Work with Groupware

    DEFF Research Database (Denmark)

    Pors, Jens Kaaber; Simonsen, Jesper

    2003-01-01

    One important goal of employing groupware is to make possible complex collaboration between geographically distributed groups. This requires a dual transformation of both technology and work practice. The challenge is to re­duce the complexity of the coordination work by successfully inte......­grating the protocol stipulating the collaboration and the ar­te­fact, in form of the groupware application, mediating the col­laboration. This paper analyses a generic groupware application that was deployed in a large financial organisation in order to support working groups distributed throughout four countries....... Using the CSCW frame­work of coordination mechanisms, we have elicited six general factors influencing the integration of the groupware application in two situations....

  14. Conformal Fermi Coordinates

    CERN Document Server

    Dai, Liang; Schmidt, Fabian

    2015-01-01

    Fermi Normal Coordinates (FNC) are a useful frame for isolating the locally observable, physical effects of a long-wavelength spacetime perturbation. Their cosmological application, however, is hampered by the fact that they are only valid on scales much smaller than the horizon. We introduce a generalization that we call Conformal Fermi Coordinates (CFC). CFC preserve all the advantages of FNC, but in addition are valid outside the horizon. They allow us to calculate the coupling of long- and short-wavelength modes on all scales larger than the sound horizon of the cosmological fluid, starting from the epoch of inflation until today, by removing the complications of the second order Einstein equations to a large extent, and eliminating all gauge ambiguities. As an application, we present a calculation of the effect of long-wavelength tensor modes on small scale density fluctuations. We recover previous results, but clarify the physical content of the individual contributions in terms of locally measurable ef...

  15. Significant Differences in Nurses’ Knowledge of Basic Wound Management

    DEFF Research Database (Denmark)

    Zarchi, Kian; Latif, Seemab; Haugaard, Vibeke B

    2014-01-01

    Wounds represent a growing healthcare problem due to an aging population. Nurses play a key role in wound management and their theoretical understanding of basic wound management may be expected to influence the quality of wound therapy fundamentally. In this study, we evaluated the level...... of knowledge of wound management in 136 Danish nurses working in 3 different settings: advanced wound care clinics, home care and general hospital departments. We found that hospital nurses had less theoretical knowledge than home care nurses and nurses working at advanced wound care clinics. We also found...... of wound management in Denmark and suggests how improvements might be achieved....

  16. Animal models of chronic wound care

    DEFF Research Database (Denmark)

    Trøstrup, Hannah; Thomsen, Kim; Calum, Henrik

    2016-01-01

    on nonhealing wounds. Relevant hypotheses based on clinical or in vitro observations can be tested in representative animal models, which provide crucial tools to uncover the pathophysiology of cutaneous skin repair in infectious environments. Disposing factors, species of the infectious agent(s), and time....... An inhibiting effect of bacterial biofilms on wound healing is gaining significant clinical attention over the last few years. There is still a paucity of suitable animal models to recapitulate human chronic wounds. The etiology of the wound (venous insufficiency, ischemia, diabetes, pressure) has to be taken...... of establishment of the infection are well defined in suitable animal models. In addition, several endpoints can be involved for evaluation. Animals do not display chronic wounds in the way that humans do. However, in many cases, animal models can mirror the pathological conditions observed in humans, although...

  17. Mammalian cell models to advance our understanding of wound healing: a review.

    Science.gov (United States)

    Vidmar, Jerneja; Chingwaru, Constance; Chingwaru, Walter

    2017-04-01

    Rapid and efficient healing of damaged tissue is critical for the restoration of tissue function and avoidance of tissue defects. Many in vitro cell models have been described for wound healing studies; however, the mechanisms that underlie the process, especially in chronic or complicated wounds, are not fully understood. The identification of cell culture systems that closely simulate the physiology of damaged tissue in vivo is necessary. We describe the cell culture models that have enhanced our understanding, this far, of the wound healing process or have been used in drug discovery. Cell cultures derived from the epithelium, including corneal, renal, intestinal (IEC-8 cells and IEC-6), skin epithelial cells (keratinocytes, fibroblasts, and multipotent mesenchymal stem cells), and the endothelium (human umbilical vein endothelial cells, primary mouse endothelial cells, endodermal stem cells, human mesenchymal stem cells, and corneal endothelial cells) have played a pivotal role toward our understanding of the mechanisms of wound healing. More studies are necessary to develop co-culture cell models which closely simulate the environment of a wound in vivo. Cell culture models are invaluable tools to promote our understanding of the mechanisms that regulate the wound healing process and provide a platform for drug discovery. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Influence of radiation crosslinked carboxymethyl-chitosan/gelatin hydrogel on cutaneous wound healing

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Xin [Beijing Key Laboratory for Solid Waste Utilization and Management, College of Engineering, Peking University, Beijing 100871 (China); Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871 (China); Department of Burns, Beijing Jishuitan Hospital, Beijing 100035 (China); Zhang, Yaqing; Zhang, Xiangmei [Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871 (China); Xu, Ling, E-mail: lingxu@pku.edu.cn [Beijing Key Laboratory for Solid Waste Utilization and Management, College of Engineering, Peking University, Beijing 100871 (China); Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871 (China); Shenzhen Key Laboratory for Polymer Science, Peking University Shenzhen Institute, Shenzhen 518057 (China); Chen, Xin, E-mail: xchin@vip.sina.com [Department of Burns, Beijing Jishuitan Hospital, Beijing 100035 (China); Wei, Shicheng [Center for Biomedical Materials and Tissue Engineering, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871 (China); Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Peking University, Beijing 100081 (China)

    2013-12-01

    A series of carboxymethyl chitosan (CM-chitosan) and gelatin hydrogels were prepared by radiation crosslinking. A pre-clinical study was performed by implantation model and full-thickness cutaneous wound model in Sprague–Dawley rats to preliminarily evaluate the biocompatibility, biodegradability and effects on healing. In the implantation test, as a component of the hydrogels, CM-chitosan showed a positive effect on promoting cell proliferation and neovascularization, while gelatin was efficient to stabilize the structure and prolong the degradation time. To evaluate the function on wound healing, the hydrogels were applied to the relatively large full-thickness cutaneous wounds (Φ3.0 cm). Compared with the control groups, the hydrogel group showed significantly higher percentage of wound closure on days 9, 12 and 15 postoperatively, which was consistent with the significantly thicker granulation tissue on days 3 and 6. All results apparently revealed that the radiation crosslinked CM-chitosan/Gelatin hydrogels could induce granulation tissue formation and accelerate the wound healing. - Highlights: • The hydrogels were prepared by a facile and green method, radiation crosslinking. • The biodegradability and mechanical strength can be regulated by composition. • The hydrogels promote fibroblasts proliferation and neovascularization. • The hydrogels lead to earlier tissue granulation and re-epithelialization. • The hydrogels are ideal wound healing materials with excellent biocompatibility.

  19. The JAK/STAT signaling pathway and photobiomodulation in chronic wound healing.

    Science.gov (United States)

    Jere, Sandy W; Abrahamse, Heidi; Houreld, Nicolette N

    2017-10-06

    Wound healing is a physiological process that occurs in overlapping phases namely hemostasis, inflammation, proliferation, and remodeling. Chronic wounds fail to proceed through these reparative processes to achieve the functional integrity within the expected time. Wound healing relies upon growth factors and cytokines for the precise and accurate regulation of cellular responses. These are achieved through the use of complex growth factor/cytokine induced signaling pathways. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway transmits extracellular signals to the nucleus for the transcription of genes involved in proliferation and differentiation, to name but a few. Photobiomodulation (PBM) is an emerging area of interest within the scientific community and researchers are currently exploring its underlying mechanism and the associated signaling pathways involved. PBM is a light based therapy making use of low powered lasers or light emitting diodes (LEDs) to enhance tissue repair, and reduce pain and inflammation. Current conventional treatments for chronic wounds are frequently associated with failure and have limited therapeutic efficacy. Thus there is a need for efficient wound healing interventions and the identification and development of new treatments is required. In this review we summarize the involvement of JAK/STAT signaling and PBM in chronic wounds. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Angelica Dahurica ethanolic extract improves impaired wound healing by activating angiogenesis in diabetes.

    Directory of Open Access Journals (Sweden)

    Xiao-Na Zhang

    Full Text Available Abnormal angiogenesis plays an important role in impaired wound healing and development of chronic wounds in diabetes mellitus. Angelica dahurica radix is a common traditional Chinese medicine with wide spectrum medicinal effects. In this study, we analyzed the potential roles of Angelica dahurica ethanolic extract (ADEE in correcting impaired angiogenesis and delayed wound healing in diabetes by using streptozotocin-induced diabetic rats. ADEE treatment accelerated diabetic wound healing through inducing angiogenesis and granulation tissue formation. The angiogenic property of ADEE was subsequently verified ex vivo using aortic ring assays. Furthermore, we investigated the in vitro angiogenic activity of ADEE and its underlying mechanisms using human umbilical vein endothelial cells. ADEE treatment induced HUVECs proliferation, migration, and tube formation, which are typical phenomena of angiogenesis, in dose-dependent manners. These effects were associated with activation of angiogenic signal modulators, including extracellular signal-regulated kinase 1/2 (ERK1/2, Akt, endothelial nitric oxide synthase (eNOS as well as increased NO production, and independent of affecting VEGF expression. ADEE-induced angiogenic events were inhibited by the MEK inhibitor PD98059, the PI3K inhibitor Wortmannin, and the eNOS inhibitor L-NAME. Our findings highlight an angiogenic role of ADEE and its ability to protect against impaired wound healing, which may be developed as a promising therapy for impaired angiogenesis and delayed wound healing in diabetes.