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Wound Model (wound + model)
Selected AbstractsAntibacterial Properties of an Iron-based Hemostatic Agent In Vitro and in a Rat Wound ModelACADEMIC EMERGENCY MEDICINE, Issue 7 2009David O. Bracho Abstract Objectives:, Topical hemostatic agents are currently employed on the battlefield for control of major hemorrhage and have potential for use in civilian settings. Some of these compounds may also be antibacterial. Given the behavior of these compounds, the purpose of this study was to assess the potential antibacterial properties of an iron oxyacid,based topical hemostatic agent against three problematic species of wound-contaminating microorganisms: Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, and methicillin-resistant Staphylococcus epidermidis. Methods:, Bacteria were treated in vitro with the test powder for 30 minutes and then assessed for viability. Long-term (8-hour) inhibition of bacterial growth was also examined. In vivo, a rat full-thickness 1-cm2 skin wound was studied. Wounds were contaminated, treated, and then quantitatively cultured 24 hours later. Results:, The lethal dose for 99% of the organisms (LD99) for the compound against each organism ranged from 0.89 (±0.28) to 4.77 (±0.66) mg/mL (p < 0.05). The compound produced sustained inhibition over 8 hours at both 1 and 5 mg/mL (p < 0.05 for each), for P. aeruginosa, S. epidermidis, and S. aureus. In vivo, activity was noted against only P. aeruginosa, with the largest magnitude reduction being on the order of 3-log colony-forming units (CFU; p < 0.01). Conclusions:, The iron-based agent studied possesses significant in vitro and lesser in vivo antibacterial effects. Further optimization of the delivery, dosing, and evaluation of this agent in a larger animal model with more humanlike skin structures may reveal important wound effects beyond control of bleeding. [source] Haemodynamic effects of ,75 mmHg negative pressure therapy in a porcine sternotomy wound modelINTERNATIONAL WOUND JOURNAL, Issue 1 2009Arash Mokhtari Abstract Previous research has shown ,125 mmHg to be the optimal negative pressure for creating an environment that promotes wound healing, and this has therefore been adopted as a standard pressure for patients with deep sternal wound infection. However, it has not yet been clearly shown that ,125 mmHg is the optimal pressure from a haemodynamic point of view. Furthermore, there have been reports of cardiac rupture during ,125 mmHg negative pressure therapy. We therefore studied the effects of a lower pressure: ,75 mmHg. Twelve pigs were used. After median sternotomy, sealed negative pressure therapy of ,75 mmHg was applied. Baseline measurements were made and continuous recording of the cardiac output, end-tidal CO2 production, mean arterial pressure, mean pulmonary pressure (pulmonary artery pressure), systemic vascular resistance, pulmonary vascular resistance, left atrial pressure and central venous pressure was started. Six pigs served as controls. No statistically significant difference was observed in any of the haemodynamic parameters studied, compared with the controls. The present study shows that, with a suitable foam application technique, ,75 mmHg can be applied without compromising the central haemodynamics. [source] Upregulation of gamma-2 laminin-332 in the mouse ear vesicant wound model,JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 3 2009Yoke-Chen Chang Abstract Epithelial cell migration during wound healing is regulated in part by enzymatic processing of laminin-332 (formerly LN-5), a heterodimer formed from ,, ,, and , polypeptide chains. Under static conditions, laminin-332 is secreted into the extracellular matrix as a proform and has two chains processed to smaller forms, allowing it to anchor epithelial cells to the basement membrane of the dermis. During incisional wounding, laminin ,2 chains in particular are processed to smaller sizes and function to promote epithelial sheet migration over the wound bed. The present study examines whether this same function occurs following chemical injury. The mouse ear vesicant model (MEVM) was used to follow the pathology in the ear and test whether processed laminin-332 enhances epithelial cell migration. Skin biopsies of sulfur mustard (SM) exposed ears for several time points were analyzed by histology, immunohistochemistry, real-time PCR, and Western blot analysis. SM exposure greatly increased mRNA levels for laminin-,2 in comparison to the other two chains. Protein production of laminin-,2 was upregulated, and there was an increase in the processed forms. Protein production was in excess of the amount required to form heterotrimeric laminin-332 and was associated with the migrating epithelial sheet, suggesting a potential role in wound healing for monomeric laminin-,2. © 2009 Wiley Periodicals, Inc. J Biochem Mol Toxicol 23:172,184, 2009; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20275 [source] The characterization and optimization of injectable silicone resin particles in conjunction with dermal fibroblasts and growth factors: An in vitro studyJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 1 2010Robert M. Crews Abstract Minimally invasive subdermal injection of liquid silicone has been used clinically to augment the soft tissue of the foot to mitigate high pressures that cause diabetic foot ulcers. However, implant migration has been a clinical issue. The objective of this study was to assess the effects of three specific concentrations of silicone resin particles (12 ,m average diameter) in conjunction with either platelet-derived growth factor (PDGF-BB) or basic fibroblast growth factor (bFGF) on fibroblast cell proliferation, collagen synthesis, cell morphology, and migration through in vitro assays and a monolayer scratch wound model. PDGF and bFGF enhanced the proliferation of fibroblasts 5.7-fold and fivefold, respectively, while the addition of silicone particles had no significant effect on proliferation. Collagen production was increased approximately twofold with the addition of bFGF and the medium concentration of particles over bFGF without particles and the PDGF groups. The addition of silicone particles had no significant effect on collagen production compared with control groups without particles. Fibroblast migration was enhanced by the addition of both PDGF and bFGF compared to controls, although slower scratch wound closure rates were observed in the presence of particles compared to controls without particles. Cell morphology suggested that particles induced cellular aggregation encircling silicone particles postwounding as well as migration into the wound area. These results suggest that silicone particles in combination with a growth factor might enhance fibroblast aggregation and implant stability, and could promote connective tissue ingrowth and implant encapsulation in the soft tissue of the diabetic foot. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010 [source] A biodegradable copolymer for the slow release of growth hormone expedites scarring in diabetic ratsJOURNAL OF BIOMEDICAL MATERIALS RESEARCH, Issue 2 2007Francisco García-Esteo Abstract In many diseases wound healing is impaired. This study was designed to establish whether the healing process in diabetes could be improved using a site-specific polymer delivery system containing hGH. The system was first optimized in in vitro experiments performed on cultured fibroblasts taken from healthy and diabetic rats and then tested in an incisional wound model created in the diabetic Wistar rat. In the in vitro experiments using cultured fibroblasts, cell viability, growth, and proliferation were determined, along with polymer degradation, hormone release rates and the expression of TGF,1 in the culture medium. For the in vivo experiments, polymer discs with/without GH were inserted through 3 cm incisions made on the backs of the animals. Wound specimens were obtained 7 and 30 days after surgery to evaluate inflammatory/apoptotic cells, metalloprotease expression and neoangiogenesis using microscopy and immunohistochemical techniques. The local administration of GH using a polymer delivery system did not affect the normal wound healing process. Conversely, when used in diabetic animals, epidermal and dermal repair was expedited. Our findings indicate that GH induces cell proliferation, enhances CD4+ infiltration; increases extracellular matrix protein deposition; stimulates angiogenesis; and diminishes apoptosis at the diabetic wound site. These effects give rise to a comparable wound healing process to that observed in healthy animals. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2006 [source] A novel flow cytometric analysis for platelet activation on immobilized von Willebrand factor or fibrillar collagenJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2 2003S. Kao Summary., Under flow conditions, platelets adhere singly or in small aggregates on von Willebrand factor (VWF)-coated surfaces, but form large aggregates on immobilized fibrillar collagen. We developed a novel flow cytometric analysis to study the mechanisms underlying these distinct platelet deposition patterns. Flow cytometry was used to measure platelet activation after platelet adherence onto microspheres coated with either VWF or collagen fibrils. Two representative indices were calculated to quantify activated GpIIb,IIIa and P-selectin expression on adherent platelets. The signaling pathways responsible for platelet activation after interacting with fibrillar collagen were elucidated using various inhibitors. An in vitro endothelial cell wound model was also used to study the roles of VWF and fibrillar collagen in platelet deposition onto subendothelial matrixes. The adherent platelets on fibrillar collagen express more activated GpIIb,IIIa and P-selectin than those on VWF. Activation of GpIIb,IIIa and expression of P-selectin after platelet interaction with collagen occur via different intracellular signaling pathways; however, Ca2+ released from intracellular pools is common to both phenomena. Platelets were deposited singly or formed small aggregates on the endothelial cell wounded area, and this deposition pattern was dependent on VWF molecules secreted by endothelial cells and the absence of subendothelial collagen fibrils. As less activated GpIIb,IIIa and P-selectin are expressed after platelets interact with immobilized VWF alone, subsequent flowing platelet recruitment is minimal. Collagen fibrils, however, can activate adherent platelets sufficiently to promote the formation of large platelet aggregates. [source] Time and Dose Effects of Mitomycin C on Extracellular Matrix Fibroblasts and Proteins,THE LARYNGOSCOPE, Issue 1 2005Bryce Ferguson Abstract Objectives/Hypothesis: The objective was to determine treatment dose and time-dependent effects of injected mitomycin C on extracellular matrix fibroblasts, collagen, and fibronectin, important mediators in the wound healing response, in a rat cutaneous wound model. Study Design: A prospective, controlled animal study. Methods: Forty rats were injected with three different doses (0.4, 2.3, and 5.0 mg/mL) of mitomycin C at three different wound sites with a fourth wound site receiving saline as a control. The rats were grouped to have their tissue harvested at five different dates ranging from 1 week to 8 weeks. After death, samples from the wound site underwent Western blot analysis for collagen and fibronectin and histological analysis measuring fibroblast apoptosis. Results: Over an 8-week period, collagen and fibronectin significantly decreased and fibroblast apoptosis significantly increased. No correlation was found between the injected dose of mitomycin C and either the extracellular matrix protein concentration or the rate of fibroblast apoptosis. Conclusion: Mitomycin C demonstrated a long-term effect in a wound, inhibiting collagen and fibronectin production and inducing apoptosis. Use of mitomycin C in excess of 0.4 mg/mL did not alter protein concentrations or rate of apoptosis. [source] Curcumin differentially regulates TGF-,1, its receptors and nitric oxide synthase during impaired wound healingBIOFACTORS, Issue 1-2 2002Haresh Mani Abstract Wound healing is a highly ordered process, requiring complex and coordinated interactions involving peptide growth factors of which transforming growth factor-beta (TGF-,) is one of the most important. Nitric oxide is also an important factor in healing and its production is regulated by inducible nitric oxide synthase (iNOS). We have earlier shown that curcumin (diferuloylmethane), a natural product obtained from the plant Curcuma longa, enhances cutaneous wound healing in normal and diabetic rats. In this study, we have investigated the effect of curcumin treatment by topical application in dexamethasone-impaired cutaneous healing in a full thickness punch wound model in rats. We assessed healing in terms of histology, morphometry, and collagenization on the fourth and seventh days post-wounding and analyzed the regulation of TGF-,1, its receptors type I (tIrc) and type II (tIIrc) and iNOS. Curcumin significantly accelerated healing of wounds with or without dexamethasone treatment as revealed by a reduction in the wound width and gap length compared to controls. Curcumin treatment resulted in the enhanced expression of TGF-,1 and TGF-, tIIrc in both normal and impaired healing wounds as revealed by immunohistochemistry. Macrophages in the wound bed showed an enhanced expression of TGF-,1 mRNA in curcumin treated wounds as evidenced by in situ hybridization. However, enhanced expression of TGF-, tIrc by curcumin treatment observed only in dexamethasone-impaired wounds at the 7th day post-wounding. iNOS levels were increased following curcumin treatment in unimpaired wounds, but not so in the dexamethasone-impaired wounds. The study indicates an enhancement in dexamethasone impaired wound repair by topical curcumin and its differential regulatory effect on TGF-,1, it's receptors and iNOS in this cutaneous wound-healing model. [source] Human lactoferrin stimulates skin keratinocyte function and wound re-epithelializationBRITISH JOURNAL OF DERMATOLOGY, Issue 1 2010L. Tang Summary Background, Human lactoferrin (hLF), a member of the transferrin family, is known for its antimicrobial and anti-inflammatory effects. Recent studies on various nonskin cell lines indicate that hLF may have a stimulatory effect on cell proliferation. Objectives, To study the potential role of hLF in wound re-epithelialization. Materials and methods, The effects of hLF on cell growth, migration, attachment and survival were assessed, with a rice-derived recombinant hLF (holo-rhLF), using proliferation analysis, scratch migration assay, calcein-AM/propidium iodide staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) method, respectively. The mechanisms of hLF on cell proliferation and migration were explored using specific pathway inhibitors. The involvement of lactoferrin receptor low-density lipoprotein receptor-related protein 1 (LRP1) was examined with RNA interference technique. An in vivo swine second-degree burn wound model was also used to assess wound re-epithelialization. Results, Studies revealed that holo-rhLF significantly stimulated keratinocyte proliferation which could be blocked by mitogen-activated protein kinase (MAPK) kinase 1 inhibitor. Holo-rhLF also showed strong promoting effects on keratinocyte migration, which could be blocked by either inhibition of the MAPK, Src and Rho/ROCK pathways, or downregulation of the LRP1 receptor. With cells under starving or 12- O -tetradecanoylphorbol-13-acetate exposure, the addition of holo-rhLF was found greatly to increase cell viability and inhibit cell apoptosis. Additionally, holo-rhLF significantly increased the rate of wound re-epithelialization in swine second-degree burn wounds. Conclusions, Our studies demonstrate the direct effects of holo-rhLF on wound re-epithelialization including the enhancement of keratinocyte proliferation and migration as well as the protection of cells from apoptosis. The data strongly indicate its potential therapeutic applications in wound healing. [source] | ||||||||||