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Gregory S Schultz

Publications and source records attributed to Gregory S Schultz.

At least 37 records · Page 2Linked to original sources
PubMed2003

Growth factor, cytokine and protease interactions during corneal wound healing.

Healing of corneal injuries is an exceptionally complex process involving the integrated actions of multiple growth factors, cytokines, and proteases produced by epithelial cells, stromal keratocytes, inflammatory cells, and lacrimal gland cells. Following corneal injury, basal epithelial cells migrate and proliferate in response to chemotactic cytokines and mitogenic growth factors, including epidermal growth factor and keratinocyte growth factor. Simultaneously, keratocytes adjacent to the injured area undergo apoptosis under the Fas/Fas ligand system, while more distant keratocytes transform into activated fibroblasts and migrate into the wound, where they begin synthesizing new extracellular matrix components that form the scar tissue under the dominant influence of the TGFb/ CTGF system. Epithelial cells and activated stromal fibroblasts also secrete growth factors and cytokines that have paracrine and autocrine functions. Corneal repair proceeds for the next several weeks to months, during which time the gene expression profile slowly returns to the pre-injury pattern and the provisional scar matrix slowly remodels by actions of matrix metalloproteinases. While minor epithelial injuries heal by regeneration of normal architecture, large stromal injuries heal by repair with irregular scar tissue that impairs the optical properties of the cornea.Also, if the integrated regulation of the wound healing process is interrupted at any point, the wound fails to heal properly and a corneal ulcer develops. Better understanding of the cellular and molecular changes that occur during repair of corneal wounds will provide the opportunity to design agents that selectively modulate key phases of corneal wound healing, resulting in scars that more closely resemble normal corneal architecture.

Journal Article↗
PubMed2003

Detection of connective tissue growth factor (CTGF) in human tear fluid: preliminary results.

PURPOSE: Connective tissue growth factor (CTGF) is one of the main regulators of fibrosis. We aimed to evaluate its presence in the human tear fluid of healthy individuals. METHODS: A total of 70 tear fluid samples were collected from eight volunteers prior to and after stimulation of reflex tears with onion vapour. Specific ELISA analysis was performed with goat IgG against human CTGF. RESULTS: Connective tissue growth factor was detected in seven samples (10%), with maximum levels of 17 ng/mL in basal tears. Induction of reflex tearing resulted in a fast and significant decrease of CTGF concentrations (r = - 0.95). No CTGF was detected in 90% of the samples. CONCLUSION: Connective tissue growth factor may occur in tear fluid in healthy human eyes. This indicates a possible role for tear fluid CTGF in ocular surface fibrosis and wound healing.

Connective Tissue Growth Factor↗
PubMed2003

Wound bed preparation: a systematic approach to wound management.

The healing process in acute wounds has been extensively studied and the knowledge derived from these studies has often been extrapolated to the care of chronic wounds, on the assumption that nonhealing chronic wounds were simply aberrations of the normal tissue repair process. However, this approach is less than satisfactory, as the chronic wound healing process differs in many important respects from that seen in acute wounds. In chronic wounds, the orderly sequence of events seen in acute wounds becomes disrupted or "stuck" at one or more of the different stages of wound healing. For the normal repair process to resume, the barrier to healing must be identified and removed through application of the correct techniques. It is important, therefore, to understand the molecular events that are involved in the wound healing process in order to select the most appropriate intervention. Wound bed preparation is the management of a wound in order to accelerate endogenous healing or to facilitate the effectiveness of other therapeutic measures. Experts in wound management consider that wound bed preparation is an important concept with significant potential as an educational tool in wound management. This article was developed after a meeting of wound healing experts in June 2002 and is intended to provide an overview of the current status, role, and key elements of wound bed preparation. Readers will be able to examine the following issues; the current status of wound bed preparation; an analysis of the acute and chronic wound environments; how wound healing can take place in these environments; the role of wound bed preparation in the clinic; the clinical and cellular components of the wound bed preparation concept; a detailed analysis of the components of wound bed preparation.

Cell Proliferation↗
PubMed2003

Alpha 1-antitrypsin and ilomastat inhibit inflammatory proteases present in human middle ear effusions.

OBJECTIVES: Proteases of both the serine and metalloproteinase families have been shown to play a role in the pathogenesis of otitis media (OM). Inhibitors of proteases from each of these families have been shown to beneficially impact disease progression in a number of related chronic inflammatory conditions, but their use has not been studied in OM. The purpose of this study was to assess the activity of the protease inhibitors recombinant alpha 1-antitrypsin (rAAT) and ilomastat on inflammatory proteases present in human middle ear effusions (MEEs), with a view to their potential utility in the treatment of OM. STUDY DESIGN: Prospective and ex vivo. METHODS: MEEs were collected from 100 patients presenting for middle ear surgery, most commonly tympanostomy tube placement or treatment of acute posttympanostomy otorrhea (APTO). MEEs were analyzed for the presence of matrix metalloproteinases (MMPs) and human neutrophil elastase (HNE) and the inhibitory activity of rAAT and ilomastat on these proteases, respectively. RESULTS: MMP levels were highest in APTO, and HNE was highest in chronic suppurative OM and APTO. High levels of MMP and HNE (>3 mAU/min) were found in 52% and 37% of MEEs, respectively. Ilomastat and rAAT demonstrated significant inhibition of MMP and HNE activity (>30% reduction), respectively, in 80% and 82% of MEEs with high levels of activity. CONCLUSIONS: Proteases are commonly found in OM. Ilomastat and rAAT are potent inhibitors of proteases in MEEs across a wide range of OM in humans. Investigation into the potential therapeutic benefits of these protease inhibitors is warranted.

Adolescent↗
PubMed2003

Protease inhibitors alpha1-antitrypsin and ilomastat are not ototoxic in the chinchilla.

OBJECTIVES: Proteases of both the serine and the metalloprotease families have been shown to play a role in the pathogenesis of otitis media. Inhibitors of proteases from each of these families have been shown to beneficially impact disease progression in a number of related chronic inflammatory conditions. The purpose of this study was to assess the safety of protease inhibitors when instilled into the middle ear, with a view to their potential use in the treatment of human otitis media. STUDY DESIGN: Prospective, randomized, controlled trial in the chinchilla model. METHODS: After completing baseline auditory testing and bilateral transpalatal obstruction of the Eustachian tube, chinchillas received weekly transbullar injections of protease inhibitor (alpha1-antitrypsin, ilomastat, or both), vehicle, or saline. After 1 month, hearing was tested and the animals were sacrificed. Temporal bone histopathologic examination was performed. RESULTS: All treatment groups demonstrated a statistically insignificant average loss in long-term hearing (0 dB) for all measures using clicks and tones (P >.15 for all conditions). All treatment groups were statistically insignificantly different from one another (P =.5625). Histopathologic examination revealed no significant inner ear changes. CONCLUSIONS: Protease inhibitors that are currently under study in animal models and humans for the treatment of inflammatory diseases that are related to imbalances between protease and protease inhibitor have no significant toxic effect on the inner ear of chinchillas. These findings support the safety of further clinical trials using these inhibitors to treat middle ear inflammation.

Animals↗
PubMed2003

Role of connective tissue growth factor in breast implant elastomer capsular formation.

Transforming growth factor-beta (TGF-beta) has been demonstrated to be a mediator in scar formation and in multiple fibrotic disorders such as in Dupuytren contractures and in pulmonary fibrosis. Recently, it has been demonstrated that connective tissue growth factor (CTGF) is a downstream mediator of TGF-beta and acts to stimulate wound contraction and fibrosis. The purpose of this study is to assess the role of CTGF in the development of breast implant elastomer capsule formation over time and to evaluate the effects of TGF-beta and CTGF antisense (AS) oligonucleotides on capsule formation. Fifteen Sprague-Dawley rats were randomly assigned to treatment (n = 12) and control (n = 3) groups. Four 2- x 2-cm pockets were created on the dorsum deep to the panniculus carnosus in each rat. A 1- x 1-cm smooth breast implant elastomer was placed. Each rat in the treatment group received 1 ml vehicle, AS-TGF-beta, AS-CTGF, or scramble antisense oligonucleotide (AS-scramble). Control rats received either 1 ml vehicle or 1 ml saline in each pocket. At weeks 1, 3, and 5, four treatment rats and one control rat were randomly selected and killed. Tissue blocks were harvested for determination of CTGF levels using the enzyme-linked immunosorbent assay technique and for hematoxylin and eosin slides to evaluate capsule formation. Levels of CTGF in capsular tissue treated with vehicle or AS-scrambled were similar and progressively increased in tissues on weeks 1, 3, and 5, compared with normal skin. At weeks 1 and 3 after surgery, levels of CTGF were suppressed in capsules treated with AS-CTGF or AS-TGF-beta compared with normal skin and with tissues treated with vehicle or AS-scramble (p = 0.002). At week 5, levels of CTGF were similar to levels in normal skin. Histological analysis revealed reduced capsular formation in samples treated with AS-CTGF or AS-TGF-beta compared with the two other treated sites. In conclusion, a single and local treatment with AS-CTGF or AS-TGF-beta at the time of surgery reduced CTGF levels in tissue and correlated with reduced capsular formation in a rat model. These data suggest a new therapeutic strategy to reduce early capsular formation based on local application of antisense oligonucleotides targeting CTFG and TGF-beta.

Animals↗
PubMed2003

Matrix metalloproteinase inhibition modulates fibroblast-mediated matrix contraction and collagen production in vitro.

PURPOSE: To investigate the effect of matrix metalloproteinase (MMP) inhibition on fibroblast-mediated matrix contraction and production. METHODS: Free-floating fibroblast-populated type I collagen lattices were prepared with human Tenon's capsule fibroblasts. Lattice areas were photographed and digitally analyzed to indicate the degree of lattice contraction. Quantitative competitive reverse transcription-polymerase chain reaction (QCRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to quantify mRNA and protein respectively for MMP-1, -2, and -3 by fibroblasts during lattice contraction. Gelatin zymography demonstrated activity of MMPs released into the conditioned medium of contracting lattices. Concentrations of the broad-spectrum MMP inhibitors ilomastat, CellTech (Slough, UK), and BB-94 were added to the contracting fibroblast-populated collagen lattices. Secreted C-terminal propeptide of type I collagen was measured in conditioned medium of contracting lattices by ELISA. Fibroblast proliferation in the presence of concentrations of ilomastat was measured by using the reagent water-soluble tetrazolium-1 (WST-1). RESULTS: During contraction of type I collagen lattices, Tenon's capsule fibroblasts expressed MMP-1, -2, and -3 mRNA and protein. Zymography demonstrated the release of four gelatinolytic species into the conditioned medium of contracting lattices (57, 72, 91, and 100 kDa). Inclusion of MMP inhibitors in the zymogram-developing buffer reduced the proteolytic activity of the detected bands. MMP inhibition (1-100 microM) significantly reduced fibroblast-mediated collagen lattice contraction (P < 0.05), and this effect was found to be reversible. Ilomastat also significantly inhibited production of collagen in a dose-dependent manner (P < 0.05). No effect on fibroblast proliferation was found in the presence of ilomastat. CONCLUSIONS: MMPs are produced during Tenon's capsule fibroblast-mediated collagen lattice contraction. Broad-spectrum MMP inhibition significantly reduced matrix contraction and production without cell toxicity. Future clinical use of MMP inhibitors may be possible, because MMP inhibition significantly reduces fibroblast functions associated with contractile scarring.

Cell Division↗
PubMed2003

Connective tissue growth factor expression and action in human corneal fibroblast cultures and rat corneas after photorefractive keratectomy.

PURPOSE: Connective tissue growth factor (CTGF) has been linked to fibrosis in several tissues. In this study, the interactions between CTGF and transforming growth factor (TGF)-beta were assessed in human corneal fibroblasts, and the levels and location of CTGF protein and mRNA were measured during healing of excimer laser ablation wounds in rat corneas. METHODS: Human corneal fibroblasts were incubated with TGF-beta1, -beta2, and -beta3 isoforms, and CTGF mRNA and protein were measured. CTGF was immunolocalized in the cultured fibroblasts by using a specific antibody. Regulation of collagen synthesis by TGF-beta and CTGF was assessed in human corneal fibroblasts with a neutralizing antibody and an antisense oligonucleotide to CTGF. CTGF mRNA and protein were measured in rat corneas up to day 21 after excimer ablation of the cornea. CTGF protein was immunolocalized in rat corneas after photorefractive keratectomy (PRK), and the presence of CTGF mRNA and protein in ex vivo rat corneal scrapings was established. RESULTS: All three TGF-beta isoforms stimulated expression of CTGF in human corneal fibroblasts, and CTGF was immunolocalized in the cells. Both TGF-beta and CTGF increased collagen synthesis in corneal fibroblasts. Furthermore, CTGF antibody or antisense oligonucleotide blocked TGF-beta-stimulated collagen synthesis. CTGF protein and mRNA increased in rat corneas through day 21 after PRK. CTGF expression was also detected in ex vivo scrapings of rat corneas. CONCLUSIONS: These data demonstrate that CTGF is expressed by corneal cells after stimulation by TGF-beta, that CTGF expression increases significantly during corneal wound healing, and that CTGF mediates the effects of TGF-beta induction of collagen synthesis by corneal fibroblasts. These data support the hypothesis that CTGF promotes corneal scar formation and imply that regulating CTGF synthesis and action may be an important goal for reducing corneal scarring.

Animals↗
PubMed2003

Evaluation of various compounds to inhibit activity of matrix metalloproteinases in the tear film of horses with ulcerative keratitis.

OBJECTIVE: To examine in vitro effects of various antiproteolytic compounds on activity of matrix metalloproteinase (MMP)-2 and -9 in the tear film of horses with active corneal ulcers. SAMPLE POPULATION: Samples of tear film obtained from the eyes of 34 horses with active ulcerative keratitis. PROCEDURE: Horses were sedated, and tear samples were collected from the lower fornix of 34 ulcerated eyes by use of capillary tubes. The protease inhibitors 0.2% EDTA, 0.1% doxycycline, 10% N-acetylcysteine (NAC), 0.1% solution of a modified dipeptide that contains hydroxamic acid (ie, ilomostat), 0.1% alpha1-proteinase inhibitor (PI), 0.5% alpha1-PI, and 100% fresh equine serum (ES) were used to treat pooled samples. Amount of latent and active MMP-2 and -9 was measured by optical density scanning of gelatin zymograms of treated and untreated tear samples. RESULTS: Pooled tear samples obtained from ulcerated eyes contained the latent and active forms of MMP-2 and -9. Compared with MMP activity in untreated samples, total MMP activity (sum of all bands detected) observed on the gelatin zymogram gels was reduced by 99.4% by EDTA, 96.3% by doxycycline, 98.8% by NAC, 98.9% by ilomostat, 52.4% by 0.1% alpha1-PI, 93.6% by 0.5% alpha1-PI, and 90.0% by ES. CONCLUSIONS AND CLINICAL RELEVANCE: We documented that EDTA, doxycycline, NAC, ilomostat, alpha1PI, and ES inhibited MMP activity in vitro. Because these compounds use different mechanisms to inhibit various families of proteases in the tear film of horses, a combination of these protease inhibitors may be beneficial for treatment of corneal ulcers in horses.

Acetylcysteine↗
PubMed2003

Preparing the wound bed 2003: focus on infection and inflammation.

Wound bed preparation is the promotion of wound closure through diagnosis of the cause, attention to patient-centered concerns, and correction of systemic and local factors that may delay healing. To enhance the evidence base that may be lacking, a review of relevant literature was conducted and combined with input from the International Wound Bed Preparation Advisory Board and the Canadian Chronic Wound Advisory Board to create an updated examination of practices. A template based on expert opinion of the clinical actions corresponding to each step in the paradigm of preparing the wound bed is presented and the effects of local factors (tissue debridement, infection or inflammation, moisture balance, and edge effect [TIME]) are discussed. This review differentiates increased bacterial burden/infection in the superficial and deep wound bed compartments from inflammation and provides a topical approach to treatment. Inflammatory conditions causing leg ulcers, including pyoderma gangrenosum and vasculitis are reviewed. The topical combination of silver with absorptive dressings has led to new therapeutic options for increased bacterial burden in the surface wound compartment. A compilation of the available systematic reviews for the treatment of infection has been included as a background for the expert opinion.

Acute Disease↗
PubMed2002

Future research directions in idiopathic pulmonary fibrosis: summary of a National Heart, Lung, and Blood Institute working group.

Idiopathic pulmonary fibrosis (IPF) is an insidious inflammatory fibroproliferative disease whose cause and course before diagnosis are unknown, and for which existing treatments are of limited benefit. The National Heart, Lung, and Blood Institute convened a working group to develop specific recommendations for future IPF research. Inflammatory and immune processes are involved in IPF pathogenesis, and current therapeutic strategies are aimed at suppressing the inflammation. Recent data suggest that the molecular processes underlying the fibrogenesis may provide new opportunities for therapeutic intervention. Specific areas of future research recommended by the working group include studies to elucidate the etiology of IPF, to develop novel diagnostic techniques and molecular diagnostics, to establish a program for identification of molecular targets for IPF treatment and identification and generation of agonists or antagonists that inhibit fibrogenesis, to foster investigations that couple the use of new technologies (e.g., laser capture microdissection, microarrays, and mass spectroscopic analysis of proteins) with data from the human genome project, to establish a national consortium of Clinical Centers of Excellence to conduct coordinated clinical and laboratory studies of well-characterized patients and patient-derived materials, and to stimulate research to develop animal models of persistent and progressive pulmonary fibrosis for evaluation of new intervention approaches.

Humans↗
PubMed2002

Inhibition of matrix metalloproteinases in gerbil cholesteatoma: preliminary findings.

OBJECTIVES: This study was conducted to examine the role of matrix metalloproteinases (MMPs) and the impact of a topical MMP inhibitor, ilomostat, on the development of tympanic membrane (TM) atelectasis in the gerbil model. METHODS: Eustachian tubes were cauterized bilaterally in 19 gerbils. Thereafter, both TMs received once-daily topical treatment for 8 weeks with ilomostat or vehicle or no treatment (n = 6 or 7 per group). TM atelectasis was serially graded, and TMs were harvested at 8 weeks. Gelatin zymograms were performed to determine MMP activity. RESULTS: The mean activity levels of proenzyme and active MMP-9 and MMP-2 and degree of atelectasis did not differ between groups. TM atelectasis did not correlate to levels of enzymes across individual samples. CONCLUSIONS: Topical application of an MMP inhibitor did not significantly prevent the development of TM atelectasis. It remains to be determined whether the use of MMP inhibitors may prevent the progression of atelectasis in humans.

Animals↗
PubMed2002

Microarray analysis of gene expression patterns during healing of rat corneas after excimer laser photorefractive keratectomy.

PURPOSE: To characterize changes over time in the genomic expression profile of rat corneas after excimer laser photorefractive keratectomy (PRK), in an effort to better understand the cellular response to injury and the dynamic changes that occur in gene expression patterns as a wound heals. METHODS: The corneal gene expression profile of 1176 genes at 3 and 7 days after PRK was determined and compared with untreated corneal gene expression patterns by interrogating commercially available cDNA arrays with labeled target cDNA prepared from pooled total RNA harvested from the respective treatment group of adult male rats. The gene expression patterns were inferred based on the hybridization intensities of the probes on the cDNA arrays. The hybridization signals were globally normalized and filtered. The data were analyzed by using hierarchical and k-means clustering algorithms before and after normalization of variances. RESULTS: Of the 1176 cDNA elements on the array, 588 consistently produced similar results in replicate experiments and comprised the data set analyzed in this work. In total, 73 genes were identified, with expression levels that differed by at least threefold at either 3 or 7 days after PRK. At 3 days after PRK, 70 genes were identified with expression levels that differed by more than threefold, compared with the expression level in untreated animals. The expression of 42 genes increased by threefold or more, whereas expression of 28 genes decreased by threefold or more. By day 7 after PRK, the number of genes displaying more than a threefold difference in expression pattern was reduced to 27 genes, 20 of which showed elevated levels, whereas 7 exhibited decreased levels. Hierarchical clustering of the 588 studied genes produced 10 clusters with correlation coefficients of 0.9 or greater. To determine whether any of the clusters were overrepresented by genes with related functions, the cumulative hypergeometric probability was calculated by obtaining the observed number of functionally related genes within each of the 10 clusters. Seven of the clusters were statistically overrepresented by one or more categories of functionally related genes, such as cell cycle regulators, transcription factors, and metabolic pathway genes. Clustering analysis of 56 genes generally considered to influence corneal wound healing produced 10 gene clusters with correlation coefficients of at least 0.9. Expression of 23 of these 56 genes increased at day 3, then decreased at day 7 to levels similar to those on day 0. These included several growth factors (VEGF, FGF, IGF-I), proteases (PAI-1, PAI-2A) and protease inhibitors (TIMP-2 and TIMP-3). Expression of nine genes increased on both days 3 and 7 compared with expression on day 0 (e.g., TGFB1, TGFBIIR, M6P/IGFR-2), and no genes decreased on both days 3 and 7, compared with day 0. CONCLUSIONS: Microarray analysis of 1176 identified 588 genes with reproducible patterns of expression in rat corneas on days 3 and 7 after PRK and 73 genes with a threefold change in expression compared with untreated corneas. Hierarchical clustering of these 588 genes identified 10 clusters of genes with very similar patterns of expression. Clustering of genes with similar patterns of expression implies a common regulatory pathway for the genes within a cluster, and identifies potential new targets for regulating corneal wound healing.

Animals↗
PubMedDate not supplied

Ratios of activated matrix metalloproteinase-9 to tissue inhibitor of matrix metalloproteinase-1 in wound fluids are inversely correlated with healing of pressure ulcers.

Previous analyses of fluids collected from chronic, nonhealing wounds found elevated levels of inflammatory cytokines, elevated levels of proteinases, and low levels of growth factor activity compared with fluids collected from acute, healing wounds. This led to the general hypothesis that chronic inflammation in acute wounds produces elevated levels of proteinases that destroy essential growth factors, receptors, and extracellular matrix proteins, which ultimately prevent wounds from healing. To test this hypothesis further, pro- and activated matrix metalloproteinases (MMP-2 and MMP-9), tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2), and the ratios of MMPs/TIMPs were assayed in fluids and biopsies collected from 56 patients with chronic pressure ulcers. Specimens included ulcers treated for 0, 10, and 36 days with conventional therapy or with exogenous cytokine therapies. Quantitative assay data were correlated with the amount of healing. The average MMP-9/TIMP-1 ratio in fluids from 56 ulcers decreased significantly as the chronic pressure ulcers healed. Furthermore, the average MMP-9/TIMP-1 ratio was significantly lower for fluids collected on day 0 from wounds that ultimately healed well (> or =85% reduction in initial wound volume) compared with wounds that healed poorly (< 50% wound volume reduction). These data show that the ratio of MMP-9/TIMP-1 levels is a predictor of healing in pressure ulcers and they provide additional support for the hypothesis that high levels of MMP activity and low levels of MMP inhibitor impair wound healing in chronic pressure ulcers.

Biopsy↗
PubMedDate not supplied

Analysis of gene expression patterns in human postburn hypertrophic scars.

Hypertrophic scars cause cosmetic disfigurement and limited mobility in burn patients. To better understand the molecular pathophysiology of hypertrophic scar formation, microarray analyses were performed on normal skin and hypertrophic scars from four burn patients. Microarray analyses were determined in an effort to identify genes whose expression discriminated between normal skin and mature, hypertrophic scars. Surgical biopsies were obtained from two pediatric and two adult patients 6 to 15 months after burn injury. Total RNA was isolated from the samples and subjected to microarray analysis using the Affymetrix U95Av2 GeneChip. Results from this analysis revealed 31 probe sets representing genes that were consistently up-regulated at least two-fold in hypertrophic scar specimens from all four patients and four probe sets that were down-regulated. The significance analysis of microarrays algorithm also identified 35 probe sets whose increased expression resulted in the hierarchal clustering of the hypertrophic scar and normal tissue, seven of which were identical to the six genes identified by paired analyses. These six genes all displayed elevated levels of expression in the scar tissue. Proteins encoded by the genes identified included germline oligometric matrix protein, matrix metalloproteinase-16, collagen type 1alpha, pleiotrophin, and thrombospondin-4. Although the results presented here suggest that there may be unique patterns of gene expression in hypertrophic scars that may be important in the evaluation and treatment of hypertrophic scarring, the results must be confirmed with larger datasets.

Adult↗
PubMedDate not supplied

The effect of topical tripeptide-copper complex on healing of ischemic open wounds.

OBJECTIVE: To evaluate the effects of topical glycyl-L-histidyl-L-lysine tripeptide-copper complex (TCC; Iamin 2% Gel; Procyte Corporation, Redmond, WA) on healing in ischemic open wounds. STUDY DESIGN: Experimental study. SAMPLE POPULATION: Twenty-four adult male Sprague-Dawley rats. METHODS: Rats were divided into 3 groups: topical TCC, topical TCC vehicle (hydroxypropyl-methylcellulose), and no treatment (control). Six-mm-diameter, full-thickness wounds were created within an ischemic bipedicle skin flap on the dorsum of each rat. Each day, for 13 days, wound margins were traced, and the TCC and TCC vehicle groups were treated topically. Tracings were scanned, and wound perimeter and area were calculated. On days 6, 10, and 13, selected wounds were biopsied and analyzed for tumor necrosis factor alpha (TNF-alpha) and matrix metalloproteinases (MMP) 2 and 9. RESULTS: A significant decrease in wound area was seen in the TCC group, but not the vehicle group, when compared with the control group on days 3 to 5, 6 to 9, and 11 to 13 and when TCC was compared with TCC vehicle on days 3 and 9. On day 13, initial wound area had decreased by 64.5% in the TCC group, 45.6% in the vehicle group, and 28.2% in the control group. On days 6, 10, and 13, TCC-treated wounds contained significantly lower concentrations of TNF-alpha and MMP-2 and MMP-9 than control wounds. CONCLUSION: Topical TCC resulted in accelerated wound healing in ischemic open wounds. CLINICAL RELEVANCE: Topical TCC is an effective stimulant of healing of ischemic open wounds in rats and may have an application for the treatment of chronic wounds in other species. Clinical evaluation of topical TCC is warranted.

Administration, Topical↗