Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “WOUND HEALING”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources
PubMed2006

A keratinocyte hypermotility/growth-arrest response involving laminin 5 and p16INK4A activated in wound healing and senescence.

Keratinocytes become migratory to heal wounds, during early neoplastic invasion, and when undergoing telomere-unrelated senescence in culture. All three settings are associated with expression of the cell cycle inhibitor p16INK4A (p16) and of the basement membrane protein laminin 5 (LN5). We have investigated cause-and-effect relationships among laminin 5, p16, hypermotility, and growth arrest. Plating primary human keratinocytes on the gamma2 precursor form of laminin 5 (LN5') immediately induced directional hypermotility at approximately 125 microm/hour, followed by p16 expression and growth arrest. Cells deficient in p16 and either p14ARF or p53 became hypermotile in response to LN5' but did not arrest growth. Plating on LN5' triggered smad nuclear translocation, and all LN5' effects were blocked by a transforming growth factor (TGF) beta receptor I (TGFbetaRI) kinase inhibitor. In contrast, plating cells on collagen I triggered a TGFbetaRI kinase-independent hypermotility unaccompanied by smad translocation or growth arrest. Plating on control surfaces with TGFbeta induced hypermotility after a 1-day lag time and growth arrest by a p16-independent mechanism. Keratinocytes serially cultured with TGFbetaRI kinase inhibitor exhibited an extended lifespan, and immortalization was facilitated following transduction to express the catalytic subunit of telomerase (TERT). These results reveal fundamental features of a keratinocyte hyper-motility/growth-arrest response that is activated in wound healing, tumor suppression, and during serial culture.

Cell Adhesion Molecules↗
PubMed1988

Suppressor cell generation during normal wound healing.

We have previously shown that 10 day healing wounds in rats contain wound mononuclear cells (WMNC) which inhibit normal lymphocyte mitogenic and allogeneic responses. In the present study we sought to further characterize the WMNC and define their mechanism of action. Polyvinyl alcohol sponges implanted in wounds were harvested and processed 10 days postwounding. The resultant WMNC suspension contained less than 15% macrophages. By FACS analysis, 69.5 +/- 11.4% (mean +/- SD of eight separate experiments) of the cells expressed the all T cell marker (W3/13), while 47.7 +/- 11.9% stained with the T helper/effector marker (W3/25) and 49.5 +/- 18.8% expressed the T suppressor/cytotoxic phenotype (OX8) (Th/Ts ratio = 0.96 +/- 0.13). When various numbers of WMNC were cocultured with 5 X 10(5) PHA-stimulated rat thymic lymphocytes, as few as 500 WMNC inhibit normal blastogenesis. Long-term (72 or 144 hr) culture of WMNC revealed that they maintain their suppressive activity. Furthermore, the conditioned media of long-term cultures also significantly suppressed thymic lymphocyte PHA blastogenesis, suggesting that the WMNC secrete suppressive cytokines. Large doses of human recombinant IL-2 or indomethacin did not abrogate the inhibitory effect of WMNC. We conclude that the healing wound is normally infiltrated by suppressor lymphocytes which generate immune inhibitory cytokines.

Animals↗
PubMed1998

Upregulation of tumor suppressor protein neurofibromin in normal human wound healing and in vitro evidence for platelet derived growth factor (PDGF) and transforming growth factor-beta1 (TGF-beta1) elicited increase in neurofibromin mRNA steady-state levels in dermal fibroblasts.

We first studied expression of neurofibromin by immunohistochemistry in scars obtained from operations involving areas of healing wounds. The results demonstrated increased immunoreactivity for neurofibromin in the fibroblastic cell population of the lesions when compared with fibroblasts of apparently healthy perilesional skin, or those of intact control skin. Furthermore, dermal fibroblasts of 19 and 34 wk-old fetuses displayed a clearly detectable immunosignal for neurofibromin. In vitro studies were designed to investigate the potential effects of selected growth factors--known to be operative in wound healing--on neurofibromin mRNA steady-state levels in cultured fibroblasts. Northern transfer analyses revealed that different isoforms of platelet derived growth factor (PDGF) exerted selective effects on the neurofibromin mRNA levels: PDGF isoform AB elevated neurofibromin mRNA levels in a concentration-dependent manner when concentrations of 0.1, 1, 10, and 30 ng per ml were used. The maximal upregulatory effect of PDGF BB was reached at a concentration of 1 ng per ml. In contrast, PDGF AA did not alter the steady-state levels of neurofibromin mRNA. As estimated by RNase protection assay, transforming growth factor-beta1 (TGF-beta1) upregulated neurofibromin gene expression when concentrations of 0.5 and 5 ng per ml were used. Reverse transcription followed by polymerase chain reaction did not detect apparent alterations in the ratio of type I/type II neurofibromin isoforms in PDGF- or TGF-beta1-treated cultures. Taken together, our results suggest that expression of tumor suppressor protein neurofibromin is upregulated in response to skin injury, and that this upregulation can be mediated through PDGF and TGF-beta.

Adolescent↗
PubMed1997

The beneficial effects of recombinant human insulin-like growth factor-I (IGF-I) on wound healing in severely wounded senescent mice.

The effects of recombinant insulin-like growth factor I (rIGF-I) on wound healing were tested using senescent and young BDF-1 mice, aged 108 weeks and 10 weeks, respectively. After inflicting a full thickness dermal burn encompassing 15% of the body surface, a skin incision, 2 cm in length, was made in the back. A silicone tube containing a piece of polyvinyl sponge was then implanted into a subcutaneous pocket in the flank to collect body fluid. An osmotic pump was buried in the abdominal subcutaneous tissue for the continuous infusion of rIGF-I, the control being treated with the solvent of IGF-I, physiological saline, only. The administration of IGF-I produced favorable effects on wound healing in the senescent mice, shown by enhanced tensile strength and an elevated concentration in the hydroxyproline of the polyvinyl sponge content. The IGF-I-treated severely wounded senescent mice healed better than their counterparts and their skeletal muscles contained more glutamine. Furthermore, they showed more enhanced cutaneous hypersensitivity towards dinitrofluorobenzene than the controls, suggesting an enhanced grade of cellular immunity. There were no conspicuous differences between the two groups of young mice. These data may suggest the beneficial effects of rIGF-I on wound healing, especially in geriatric surgery.

Age Factors↗
PubMed1979

Wound healing: a review. II. Environmental factors affecting wound healing.

A variety of factors, both intrinsic and extrinsic, may influence the healing of wounds. Some of these influences are environmental in nature and subject to advantageous manipulation by the practitioner. In this article, the role of humidity, temperature, infection and oxygen tension on the process of wound healing will be discussed.

Bacterial Infections↗
PubMed1992

Insulin-like growth factors I and II expression in the healing wound.

Demonstrating temporal variation in the expression of messenger RNA (mRNA) for growth factors may give some indication as to whether growth factor synthesis is regulated in wound healing. The aim of this study was to evaluate the expression of insulin-like growth factors (IGF) I and II in the wound. Two wound models, an incisional model and a subcutaneous sponge implant model, were used in this study. The RNA was extracted and reverse transcribed and mRNA was amplified using polymerase chain reaction (PCR). Semiquantitation of PCR products was accomplished using [3H]dGTP incorporation. Levels of expression for both IGF-I and -II were found to be low in unwounded skin and at 12 hr postwounding. However, in both wound models expression increased substantially from 1 to 21 days postwounding. Both factors also were found to be expressed by fibroblasts and polymorphonuclear leukocytes (PMN). Additionally, two transcripts were found for IGF-II, the larger of which appeared to be specific for PMN and possibly cells involved in angiogenesis. Levels of message expressed in healing wounds for IGF-I and -II appear to be regulated with the highest levels of message found at time points coinciding with fibroblast predominance in the wound. Since fibroblasts are known to both secrete and respond to IGF-I, it is possible that IGF-I and IGF-II are acting to influence fibroblast differentiation and function in the later stages of wound healing.

Animals↗
PubMed2003

Essential involvement of IL-6 in the skin wound-healing process as evidenced by delayed wound healing in IL-6-deficient mice.

To clarify interleukin (IL)-6 roles in wound healing, we prepared skin excisions in wild-type (WT) and IL-6-deficient BALB/c [knockout (KO)] mice. In WT mice, the wound area was reduced to 50% of original size at 6 days after injury. Microscopically, leukocyte infiltration was evident at wound sites. Furthermore, the re-epithelialization rate was approximately 80% at 6 days after injury with increases in angiogenesis and hydroxyproline contents. The gene expression of IL-1, chemokines, adhesion molecules, transforming growth factor-beta1, and vascular endothelial growth factor was enhanced at the wound sites. In contrast, the enhanced expression of these genes was significantly reduced in KO mice. Moreover, in KO mice, the reduction of wound area was delayed with attenuated leukocyte infiltration, re-epithelialization, angiogenesis, and collagen accumulation. Finally, the administration of a neutralizing anti-IL-6 monoclonal antibody significantly delayed wound closure in WT mice. These observations suggest that IL-6 has crucial roles in wound healing, probably by regulating leukocyte infiltration, angiogenesis, and collagen accumulation.

Acute-Phase Proteins↗
PubMed2006

The basic science of wound healing.

Understanding wound healing today involves much more than simply stating that there are three phases: "inflammation, proliferation, and maturation." Wound healing is a complex series of reactions and interactions among cells and "mediators." Each year, new mediators are discovered and our understanding of inflammatory mediators and cellular interactions grows. This article will attempt to provide a concise report of the current literature on wound healing by first reviewing the phases of wound healing followed by "the players" of wound healing: inflammatory mediators (cytokines, growth factors, proteases, eicosanoids, kinins, and more), nitric oxide, and the cellular elements. The discussion will end with a pictorial essay summarizing the wound-healing process.

Cell Proliferation↗
PubMedDate not supplied

Platelet derived wound healing factors (PDWHF) accelerate and augment wound healing angiogenesis in the rat.

The object of this study was to determine the effect of PDWHF on wound healing angiogenesis. Sponges saturated with PDWHF were implanted in rats. Six hours to 14 days post-implantation, vascular corrosion casts were prepared and examined by SEM. Leukocyte margination and angiogenesis was accelerated by 24-48 hours. Vessel number was also greater than in the controls. Another series of PDWHF treated sponges were implanted. Fourteen days later the vasculature was perfused with Evans blue. Sponges were homogenized, and absorbance of the supernatants was determined. Absorbances of PDWHF supernatants was 2X greater than controls. PDWHF enhanced wound healing angiogenesis in the rat.

Animals↗
PubMed2004

[Expressions of NOS isoforms and roles of NO during skin wound healing].

Skin wound healing is an organized process for keeping cutaneous integrity, which needs the complicated interaction between inflammatory cells and biochemical mediators. Nitric oxide synthase (NOS) isoforms, as important factors during skin wound healing, synthesize nitric oxide (NO) which may be involved in the whole event of skin wound healing and play important roles in cell proliferation, differentiation and apoptosis, angiogenesis, matrix deposits and remolding. Furthermore, NO also exerts effects in some cutaneous diseases. In the present paper, the expressions of NOS isoforms and the roles of NO during skin wound healing were reviewed with references to the advances in the studies on skin wound healing. It is suggested that nitric oxide synthases, play significant parts during skin wound healing, which is worthy of further investigation.

Apoptosis↗
PubMedDate not supplied

Use of the wound healing trajectory as an outcome determinant for acute wound healing.

Accurate and clinically practical methods for measuring the progress of acute wound healing is necessary before interventions designed to optimize and even accelerate acute wound healing can be applied. Complete wound closure rates and operative wound closure severity are irrelevant to most acute wounds since most are closed at the time of primary tissue repair and remain closed throughout healing. Analogous to chronic wound closure, the rate of increase of incision tensile strength progressively decreases as time passes and 100% unwounded tissue strength is never achieved making the endpoint definition of "healed" vague. Conceptualizing acute wound healing in terms of its design elements with reintegration into a final outcome lends itself to the description of acute wound healing as a mathematical trajectory. Frequently such an equation is a rate expressing the change in an acute healing parameter, most often tensile strength, over time. Such an approach also normalizes misinterpretations in analysis or errors in theory developed by measuring healing parameters at fixed points in time. Distributions of fractional strength gain times (e.g., 85% normal strength) can be determined using statistical methodology similar that used for failure time of survival analysis. Preclinical studies show that acute wound healing trajectories can be shifted to the left from a "normal" or "impaired" curve to an accelerated or more "ideal" curve. A useful method for measuring acute wound healing outcomes is therefore required before the basic science of acute wound healing is inevitably applied to the problem of acute surgical wounds.

Acute Disease↗
PubMed2000

Bioactive interleukin-8 is expressed in wounds and enhances wound healing.

BACKGROUND: Wound healing is a sequential biological process that involves the integration of chemotaxis of neutrophils, mitosis and migration of keratinocytes, and remodeling of the scar, all of which are regulated by specific soluble mediators. To modulate wound healing specific mediators have to be identified and functionally characterized. Therefore we addressed this study on the polymorphonuclear leukocyte (PMN) attractant interleukin-8 (IL-8) and its function in epidermal wound healing. MATERIALS AND METHODS: Peptide purification, bioassays for PMN chemotaxis, and sequential IL-8 measurements were performed on human wound fluid from burn blisters and skin graft donor sites. Histology for IL-8 immunoreactivity was included. In vitro human keratinocytes were assayed for proliferation, migration, and integrin expression after IL-8 treatment. Wounding experiments with topical IL-8 were performed in a chimeric mouse model. RESULTS: IL-8 was found to be the major bioactive chemoattractant for PMNs in human blister and skin graft donor site wound fluids (mean levels ranging from 173 ng/ml Postoperative Day (POD) 1 to 2130 ng/ml (POD 5)). Released intracellular epidermal IL-8 immunoreactivity at the wound edge was considered as an immediate source of IL-8 while NH(2)-terminal analysis revealed the 77-amino-acid residue form as a second source of IL-8 possibly PMN derived. In vitro experiments on the effect of recombinant human (rh) IL-8 on keratinocyte proliferation revealed a rise in cell number (4.8-fold, ED(50) = 0.6 ng/ml), which was accompanied by an increase in cells in S phase and overexpression of the integrin subunit alpha6. In vivo topically applied IL-8 (1 microg/ml) on human skin grafts in a chimeric mouse model enhanced reepithelialization in IL-8 treated animals over controls due to elevated numbers of mitotic keratinocytes. Wound contraction was significantly diminished by topical IL-8. CONCLUSIONS: These results indicate the sequential function of endogenous IL-8 in all phases of human wound healing. Topical IL-8 may be useful in impaired wound healing.

Animals↗
PubMed2006

Androgens modulate the inflammatory response during acute wound healing.

Impaired wound healing states in the elderly lead to substantial morbidity and mortality, and a cost to the health services of over 9 billion dollars per annum. In addition to intrinsic ageing processes that per se cause delayed healing, studies have suggested marked differences in wound repair between the sexes. We have previously reported that, castration of male mice results in a striking acceleration of local cutaneous wound healing and dampens the associated inflammatory response. In this study, we report that systemic 5alpha-reductase inhibition, which blocks the conversion of testosterone to its more active metabolite 5alpha-dihydrotestosterone, mimics the effects of castration in a rat model of cutaneous wound healing. The mechanisms underlying the observed effects involve a direct, cell-specific upregulation of pro-inflammatory cytokine expression by macrophages, but not fibroblasts, in response to androgens. Androgens require the transforming growth factor beta signalling intermediate Smad3 to be present in order to influence repair and local pro-inflammatory cytokine levels. That reducing 5alpha-dihydrotestosterone levels through 5alpha-reductase antagonism markedly accelerates healing suggests a specific target for future therapeutic intervention in impaired wound healing states in elderly males.

Aged↗
PubMed2002

Androgen receptor-mediated inhibition of cutaneous wound healing.

Impaired wound healing states in the elderly lead to substantial morbidity, mortality, and a cost to the US Health Services of over $9 billion per annum. In addition to intrinsic aging per se causing delayed healing, studies have suggested marked sex-differences in wound repair. We report that castration of male mice results in a striking acceleration of local cutaneous wound healing, and is associated with a reduced inflammatory response and increased hair growth. Using a hairless mouse model, we have demonstrated that testosterone reduction stimulates the healing response not through hair follicle epithelial/mesenchymal cell proliferation, but directly via effects on wound cell populations. We suggest that endogenous testosterone inhibits the cutaneous wound healing response in males and is associated with an enhanced inflammatory response. The mechanisms underlying the observed effects involve a direct upregulation of proinflammatory cytokine expression by macrophages in response to testosterone. Blockade of androgen action systemically, via receptor antagonism, accelerates healing significantly, suggesting a specific target for future therapeutic intervention in impaired wound healing states in elderly males.

Adult↗
PubMed1994

Effects of nutrition on wound healing.

Optimal wound healing and its close relationship to a patient's positive nutritional balance is well known. For years, physicians have attempted to improve the metabolic status of patients after surgery or trauma. Currently, major emphasis is placed on perioperative nutritional status and its effect on postoperative wound healing. The intricacies of metabolism and healing are areas of current active research, in an effort to advance the quality of patient care. For the head and neck surgeon, wound healing is of paramount concern in areas of tumor extirpation, head and neck reconstruction, and maximization of postoperative functional recovery. To better explain why adequate nutrition is important in postoperative wound healing, we will provide a brief synopsis of nutrition and its relationship to wound healing.

Carbohydrate Metabolism↗
PubMed2000

Low-level laser therapy for wound healing: feasibility of wound dressing transillumination.

OBJECTIVE: The purpose of this study was to assess the feasibility of exposing wounds during low-level laser therapy (LLLT) by transillumination of the wound dressings. BACKGROUND DATA: LLLT has been associated with accelerated wound healing in chronic ulcers. The usual approach is to remove wound dressings prior to exposure and to treat three to five times weekly. Frequent change of wound dressings is time consuming and costly; it disrupts the healing process, increases the risk of wound infection, and may be traumatic for the patient. METHODS: A double integrating sphere setup was employed to quantify the diffuse transmittance and reflectance of various wound dressings. Differences in transmittance for large area sources and point sources were demonstrated through the use of a diode laser and an incoherent light source. RESULTS: There were a number of gels and membrane style wound dressings with diffuse transmittance of more than 50%. Hence, for these dressings the prescribed radiant exposure to the wound surface could be achieved by increasing the exposure duration, while maintaining reasonable overall treatment times. CONCLUSIONS: Although LLLT by transillumination of wound dressings is feasible for a variety of wound dressings without significant commitments in additional treatment time, the specific transmission of products not included in this study needs to be determined at the intended treatment wavelength. A transillumination approach may facilitate a faster rate of wound healing than LLLT applied to exposed wounds by reducing trauma and the risk of infection.

Absorption↗