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Long-term results and reasons for failure of intranasal endoscopic dacryocystorhinostomy.

The aim of this study was to evaluate the long-term results and the factors influencing the success in patients with nasolacrimal duct obstruction treated with intranasal endoscopic dacryocystorhinostomy (DCR) and silicone tube intubation (STI). We prospectively investigated 158 patients with lacrimal obstruction in two groups, one of which comprised 108 patients treated primarily with intranasal endoscopic DCR by experienced surgeons and the other comprised 50 patients who were operated on by inexperienced surgeons. In a mean follow-up time of 49 months the surgical success was 94.4% in experienced hands and 58.0% in inexperienced hands. The endoscopic examination of six patients with failure in the first group revealed granulation tissue around the tube in four, atonic sac in one and persistence of bone that was supposed to have been excised in the nasal cavity in one. There were 21 failures out of 50 patients in the second group: granulation tissue in 2 cases, fenestration to the nasolacrimal duct instead of the sac in 6 cases, synechia between the lateral nasal wall and the middle turbinate in 2 cases, bony spicles causing obstruction in 5 cases and fenestration anterior to the sac in 2 cases. In 4 cases no reasons were found for failure, but perhaps the small fenestration and failure to remove the medial half of the membranous sac wall was the reason. DCR and STI can be performed for primary treatment in lacrimal obstruction. There is a learning curve for the operation. False localization of the lacrimal sac, granulation tissue formation around the tubes, retained bony spicles, inadequate removal of the medial wall of the sac and the synechia between the lateral wall and the middle turbinate are the most common causes of failure.

Adult↗

A comparison of mucosal incisions made by scalpel, CO2 laser, electrocautery, and constant-voltage electrocautery.

This study compares the histologic effects of scalpel, CO2 laser, electrosurgery, and constant-voltage electrosurgery incisions on the mucosal tissue of swine. Tissue studies comparing the CO2 laser with the scalpel and electrosurgery have been done. However, a gross and histologic comparison of the effects of all three techniques on oral mucosal tissue has not been reported. A swine model of both tongue and buccal mucosa was used to compare the scalpel, CO2 laser, electrosurgery unit, and constant-voltage electrosurgery unit in an effort to assess their value in oral surgery. Tissue samples of tongue and buccal mucosal incisions and excisions were histologically examined at 0, 3, 7, 14, 28, and 42 days after surgery to evaluate tissue damage and wound healing properties induced by the four instruments. The instruments were also evaluated for performance and ease of use. On subjective evaluation of ease of use, constant-voltage electrosurgery scored highest (p < 0.05) on a scale of 0 to 4, followed by the CO2 laser. Speed of incisions and excisions, measured in seconds, was fastest with the scalpel (p < 0.001) and electrosurgery unit (p < 0.05). The amount of bleeding, as evaluated on a scale of 0 to 4, was least for electrosurgery (p < 0.001) and CO2 laser (p < 0.001). Histologic damage, as expected, was least with a scalpel. The extent of epithelial damage lateral to the wound edge and the extent of collagen denaturation were the lowest with the scalpel (p < 0.001), followed by constant-voltage electrosurgery. The wounds created by all four instruments displayed intact epithelium by 4 weeks, and granulation tissue peaked at 4 weeks with all methods except constant-voltage electrosurgery, where granulation tissue was still prevalent at week 6. Constant-voltage electrosurgery and the CO2 laser provided the best combination of ease of use, hemostasis, and lack of tissue injury among the instruments compared. Incisions and excisions made with constant-voltage electrosurgery required less time than those made with the laser, but constant-voltage electrosurgery wounds also had significantly more granulation tissue in later weeks of the study, suggesting that wound healing may be delayed.

Animals↗

Seasonal cryptogenic organising pneumonia with biochemical cholestasis: a new clinical entity.

The term cryptogenic organising pneumonia has been used for the combination of dyspnoea, cough, pleuritic pain, widespread shadows on chest radiographs, and histological evidence of intra-alveolar organisation with buds of granulation tissue within the alveoli. We report 12 patients with seasonal recurrence of this disorder for between 3 and 11 years. In all 12 patients, symptoms recurred between late February and early May every year, tending to increase in severity each year, and resolved between June and January. Chest radiography and computed tomography showed bilateral consolidation. Lung biopsy samples showed intra-alveolar buds of granulation tissue. There were many neutrophils within the lumina of medium-sized airways and terminal bronchioles showed evidence of obstruction by granulation tissue. Functionally, the predominant defect was restrictive and only 2 patients (life-long non-smokers) had airflow limitation. All 12 patients had very high activities of liver enzymes, suggesting intrahepatic cholestasis, but no other evidence of liver disease. Cultures of blood, sputum, lung tissue, and bronchoalveolar lavage fluid, viral screening, and complement fixation tests were consistently negative. In all patients all abnormalities responded rapidly to oral steroid therapy. These findings suggest a seasonal syndrome of organising pneumonia and biochemical abnormalities indicative of intrahepatic cholestasis. No aetiological factor has been identified, but the nature and periodicity of the illness point to an inhaled agent present in the environment for a limited period every year.

Adult↗

Glass-ionomer cement as retrograde filling material. An experimental investigation in monkeys.

The tissue reaction following the use of glass-ionomer and amalgam, as retrograde filling materials was investigated in an experimental study using 8 monkeys. After apicectomy of the upper central incisors, amalgam and glass-ionomer cement was used at random as retrograde filling material. 2 animals at a time were sacrificed after 2 weeks, 1, 3 and 6 months. Irrespective of the length of time, the tissue reactions were similar for the 2 materials. 2 weeks after surgery, a vascular granulation tissue containing lymphocytes, plasma cells and polymorpho-nucleated leukocytes was observed close to the retrograde fillings. 1 month after surgery, good healing was found, the granulation tissue being replaced by new osteoid or bone formation. After 3 and 6 months, there was complete healing with no inflammatory reaction and a mature alveolar bone surrounding the apicectomized roots.

Animals↗

PRODUCTION OF AN ANTI-INFLAMMATORY SUBSTANCE AT A SITE OF INFLAMMATION.

The anti-inflammatory effect of various substances was measured in rats implanted with cotton wool pellets. Injection or implantation of irritant materials decreased the deposition of granulation tissue on the pellets. As the amount of irritant material increased there was a corresponding decrease in the amount of tissue deposited on the pellets. There is evidence that this could not be explained by a limit to the amount of granulation tissue available within the body, and competition for it between the cotton pellets and the implanted substances. An alternative hypothesis that an anti-inflammatory substance is produced at the site of irritation (the site of implantation of the irritant substance, such as polyester sponges) was investigated. The evidence obtained supports this hypothesis. Inflammatory exudate, squeezed from polyester sponges which had been implanted subcutaneously in the backs of adrenalectomized rats. The substance responsible for this effect is probably not a steroid, and is not normally present in the plasma of adrenalectomized animals. There is, however, some (although not conclusive) evidence that it is present in the plasma of animals in which sponges have been implanted. It does not appear to be produced by incubation in vitro of plasma with sponge. The significance of these observations is discussed.

Adrenalectomy↗

Tissue reaction after subcutaneous injection of Taenia saginata oncospheres.

After subcutaneous injection of T. saginata oncospheres, a slight swelling is visible at the site of injection first after 13 days. Conspicuous projecting nodes appear after 3-4 weeks. Histological examinations of the site of injection revealed the following changes: On days 3 and 4 p.i.--edema, focal necrosis and haemorrhage, exudation of leukocytes, activation of monocytes and fibroblasts. On day 7 p.i.--in addition to edema and foci of eosinophiles, a striking activation of monocytes and fibroblasts, focal accumulation of macrophages, proliferation of blood capillaries and formation of collagen. On day 10 p.i.--eosinophiles and light macrophages around the larvae, fibroplastic granulation tissue at the periphery and collagenous connective tissue abundant. Hyperplasia of lymphoid tissue starts to appear at this time. On days 13-14 p.i.--a large amount of newly formed connective tissue in granulation tissue, diffuse infiltration of eosinophiles and hyperplasia of lymphatic tissue. On days 19-34 p.i.--haemorrhage around the cysticerci, activation of macrophages, phagocytizing erythrocytes. Endothelia of blood capillaries proliferate; lymphatic follicles are formed at the periphery of nodular affection which appears after inoculation of oncospheres. On day 34 p.i.--distinct formation of a pseudocyst. At the period from 53th to 61st day after injection, there is a mature collagenous connective tissue among the cysts, but still strongly infiltrated with cells. Clusters of siderophages are visible in connective tissue septa between the cysts.

Animals↗

Stenting in experimental laryngeal injuries.

This experimental pilot project studies acute laryngeal injuries in 20 dogs and compares the use of three types of stenting materials with using no stent at all following the production of a "controlled airway deforming injury." Each injury was repaired meticulously using stainless steel wire to immobilize the cartilage separations, and fine catgut to close the mucosal lacerations. Animals were killed after observation for periods of two to six weeks postoperatively. Marked infection, ulceration, and granulation tissue formation were observed in most of the stented animals, with the nonstented animals showing the most complete and uncomplicated healing. In this experimental model, acute laryngeal "fractures" were adequately stabilized by suturing and a stable cartilaginous framework supported the healing intralaryngeal soft tissues. Avoidance of stenting in this animal series appears to decrease infection, ulceration, and granulation tissue formation resulting in improved healing.

Acute Disease↗

Influence of irradiation on collagen content during wound healing in diabetic rats.

The aim of the present experimental research was to investigate the effects of electron irradiation on the collagen content and on the organization of the granulation tissue of skin, in diabetic rats. In this study, 48 Wistar rats were assigned to 4 groups: control, irradiated, diabetic and irradiated diabetic. First, diabetes mellitus was induced in the last two groups, by means of a single intravenous injection of streptozotocin. Fifteen days later, all animals underwent a surgery in order to create an excisional wound on their anterior dorsal skin. On the third post-operative day, only an approximately 1-cm-wide area around the wounds was exposed to 1 Gy of 6 MeV electron beam radiation, which was delivered in a single dose. Wound healing was examined by means of polarized light microscopy at 4-, 7-, 13- and 21-day time intervals after wounding. Based upon an essentially qualitative evaluation, it was possible to conclude that local electron irradiation and diabetes' associated dysfunctions caused a decrease in the collagen content of newly-formed tissue, which was more pronounced in irradiated diabetic animals. The macromolecular organization of granulation tissue was delayed in irradiated, diabetic and irradiated diabetic animals, in relation to what was observed in control animals.

Animals↗

Incorporation of microporous Teflon tracheal prostheses in rabbits: evaluation of surgical aspects.

Because tracheal prostheses made of nonporous silicone rubber develop granulation tissue at the anastomoses, we tested a prosthesis made of a microporous material (polytetrafluoroethylene, Teflon) to see whether this problem could be avoided and the prosthesis could be successfully incorporated (luminal side covered by connective tissue and epithelium). At various times after implantation in the cervical trachea of rabbits, the prostheses were inspected macroscopically for obstruction of the prosthesis lumen (lumen reduced by one-third or more) and microscopically for incorporation and inflammatory reaction (concentration of inflammatory cells) of the prosthesis. The prosthesis was successfully incorporated within 2-4 weeks in most rabbits without granulation tissue at the anastomoses. Two complications were infection of the prosthesis before incorporation was completed and obstruction of the lumen in the center of the prosthesis by granulation tissue or a deformed prosthesis wall. Both problems can be overcome, the first by giving an appropriate antibiotic for a longer period and the second by making a stiffer prosthesis. Thus, the microporous Teflon prosthesis is potentially useful as a tracheal prosthesis in rabbits.

Animals↗

[Wound management with vacuum therapy].

Vacuum assisted wound closure (VAC) is a closed system, which applies negative pressure to the wound tissues. Basic studies have shown beneficial effects on wound blood flow and proliferation of healing granulation tissue. Theoretically, the method acts by removal of excess tissue fluid from the extravascular space, which lowers capillary after-load and thereby promotes the microcirculation during the early stages of inflammation. Additionally, the mechanical effect of the vacuum on the tissue at the wound surface appears to have an "Ilizarovian" effect resulting in an exuberant proliferation of healing granulation tissue. This technique has been used in over 2560 patients at the author's institution over the past 10 years for an expanding list of wound applications in several surgical disciplines. Commonly used orthopedic indications include traumatic wounds following débridement, infection (following débridement), fasciotomy wounds for compartment syndrome, and as a dressing for anchoring an applied split thickness skin graft. The author's personal experience consists of 269 patients treated and has not been associated with any major complications. A low incidence (2.5%) of localized superficial skin irritation occurred when a portion of the vacuum sponge overlapped the affected area. This problem is avoided by carefully confining the sponge to the wound tissue and avoiding the overlap of normal skin. The technique is contraindicated in patients with an allergy to any of the components which contact the skin such as the polyurethane sponge, the adhesive, or the plastic film applied to seal the system to the skin around the wound. Patients whose skin is thin and easily damaged will not tolerate the pulling off of the adhesive film, which is done at the time of sponge removal/change. Also, patients who are fully anticoagulated or patients with large wound surface areas (e.g., burns) may need careful monitoring of electrolytes, hematocrit, and/or fluid balance in an intensive care or burn unit setting. The mainstay of wound care is débridement, and vacuum assisted wound closure is not a substitute for this. It is a novel and welcome addition to the methods available to surgeons charged with the management of challenging wounds, and its final role in the overall list of adjunctive wound treatment modalities is still seeking a final definition.

Cell Division↗

Otologic effects of topical mitomycin C: phase I-evaluation of ototoxicity.

HYPOTHESIS: To determine ototoxicity of topical mitomycin C when placed in the middle ear at varying concentrations. BACKGROUND: Despite meticulous surgical technique and diligent postoperative care, some patients develop excessive scar and granulation tissue in the middle ear or mastoid cavity. Poor wound healing may result in infection, tympanic membrane perforation, or conductive hearing loss, which may necessitate further surgery. Use of topical mitomycin C in the ear may be beneficial in reducing scar and granulation tissue formation. This phase of the study was developed to determine the safety of topical mitomycin C in the rat model relative to ototoxicity. METHODS: Twelve Sprague-Dawley rats were evaluated with auditory brainstem response testing before and after treatments. Topical mitomycin C was injected in the middle ear of the right ear of eight animals. Varying concentrations of 0.125 to 0.5 mg/ml were used. Saline was injected in the left ear of each animal to serve as a control. Four separate animals were evaluated with placement of topical mitomycin C on Gelfoam into the middle ear. In two animals, Gelfoam was placed in the middle ear for 1 minute and then removed. In two animals, Gelfoam was placed in the middle ear and left in place. Auditory brainstem response testing was performed at 4 weeks and at 8 weeks. RESULTS: Using a high concentration of mitomycin C (>0.25 mg/ml) resulted in ototoxicity, with an increase in the auditory brainstem response threshold at 4 weeks and at 8 weeks. At low concentrations (<0.20 mg/ml), no change in auditory brainstem response threshold was noted. Animals treated with Gelfoam soaked in mitomycin C showed no change in auditory brainstem response threshold. CONCLUSION: The results of this study indicate that topical mitomycin C on Gelfoam applied in the middle ear appears safe when low concentrations are used, even in the rat, which has a higher susceptibility to gentamycin toxicity than humans. Higher concentrations may lead to ototoxicity based on changes in Wave V on auditory brainstem response. This treatment may prove to be an important option for patients suffering from chronic granulation tissue or scar tissue in the external or middle ear.

Administration, Topical↗

Angiogenesis in wound healing and tumor metastasis.

Formation of new blood vessels is essential for several physiological and pathological events, e.g. embryogenesis, wound healing and tumor growth and metastasis. In order to increase the insight into the mechanisms of angiogenesis we have visualized the different components of the microvasculature in human wounds and tumors by immunohistochemistry on the light and electronmicroscopic level. For this purpose, antibodies recognizing distinct markers for human endothelial cells, pericytes and basal lamina were used on freshly frozen or paraformaldehyde-fixed tissue samples. In terms of efficacy, the PAL-E antigen is highly specific for blood vessel endothelium. Its sensitivity is less than other endothelial markers, such as von Willebrand factor and CD 31, as it is not expressed in arterioles. Within the context of the microvasculature alpha-smooth muscle actin and the HMW-MAA chondroitin sulphate proteoglycan are useful markers for pericytes. Type IV Collagen and Laminin can be visualized consistently in the microvascular basal lamina. During the formation of granulation tissue in wound healing a heterogeneity of the expression of endothelial and pericyte markers is found. In the least matured zone in granulation tissue of decubitus lesions and experimental skin wounds microvessels already contained both endothelial cells and pericytes, suggesting a role for both cell types in the early steps of angiogenesis. Regarding the tumor microvasculature, antibodies to von Willebrand factor often failed to stain capillaries, that did show expression of the other endothelial markers studied. Broad staining in pericytes was found for the HMW-MAA chondroitin sulphate proteoglycan. In contrast, these cells only locally expressed alpha-smooth muscle actin. Staining of the basal lamina components Type IV Collagen and Laminin within tumors was not restricted to the microvasculature. Therefore, antibodies recognizing endothelial markers, particularly PAL-E and BMA 120, are preferable as tools to visualize the tumor microvasculature. In accordance with the situation in granulation tissue of wound healing the broad presence of pericytes in the microvasculature of human tumor suggests an involvement of this cell type in tumor angiogenesis. Recent immunohistochemical studies on human tumor lesions indicated that a high number of microvessels adjacent to the tumor as a measure of tumor angiogenesis is an unfavorable prognostic factor in cutaneous melanoma, mammary carcinoma and non-small cell pulmonary carcinoma. This new application of immunohistochemistry represents a valuable, clinically relevant adjunct to the repertoire of the surgical pathologist.

Animals↗

Cadaveric allograft as adjunct therapy for nonhealing ulcers.

The objective of this study was to describe the results of a retrospective survey of 27 patients who were treated with cadaveric skin allograft as an adjunct therapy for wound management. The evolution, benefits, indications, and future of cadaveric skin allografts are also discussed. Glycerin-preserved, frozen, cadaveric split-thickness skin allograft was sutured to excised wounds and held in place with a stent dressing. Retrospective data recovered from wound assessment forms and progress reports were used to evaluate the effectiveness of this treatment. The etiology, pre- and postexcisional volume, depth of debridement, time taken for granulation tissue to first appear, allograft life span, volume post allograft removal, healing time, time expired from allograft to skin grafting, and reported pain were documented and presented. A total of 34 ulcers in 27 patients of various etiologies were evaluated. Pre-excisional volume averaged 6448.2 mm3, while the volume post allograft debridement averaged 9159.0 mm3. The length of time the biologic dressing remained in place averaged 29.1 days. Granulation tissue became first apparent through the fenestrations in the graft at an average of 13.4 days. Pain was notably reduced in 53% of the patient's post debridement with application of allograft. Only 12% of the patients experienced an increase in pain and 35% related no change. Most (65%) of the patients healed via secondary intention. The rest (35%) underwent split-thickness skin grafting. The average healing time was 113.9 days. No infections occurred while the allograft was in place. Lower extremity wounds present many challenges that may lengthen the course of treatment. As healing time increases, so too does the risk of various complications such as infection, desiccation, and damage to underlying soft tissues. The benefits of allograft treatment are particularly noteworthy in areas where bone and/or tendon are exposed. In these cases it becomes especially difficult to promote granulation tissue growth. Cadaveric skin allografts aid in preventing desiccation, help to control infection, and can substantially reduce patient discomfort.

Bandages↗

Histological findings in infantile otoantritis.

The histopathological findings in the granulation tissue removed at mastoidectomy from 34 infants between 1971 and 1974 are described. Granulation tissue was present in every case, characterized by the histological features of chronic inflammation and fibrosis (sclerosis), although the process was of short duration. The great number of thick fibers was a surprising finding. To prevent fibrosis (sclerosis) to develop later on, it is advisable to operate as early as indicated.

Anti-Bacterial Agents↗

Tympanic membrane/middle ear pathologic correlates in chronic otitis media.

OBJECTIVE: To correlate pathologic findings of the tympanic membrane with pathologic changes in the middle ear cleft in chronic otitis media. STUDY DESIGN: Retrospective. MATERIAL AND METHODS: One hundred-fifty temporal bones from 97 subjects with chronic otitis media (defined as middle ear pathologic changes including granulation tissue, fluid, cholesteatoma, cholesterol granuloma, tympanosclerosis, and ossicular changes) were selected to correlate the presence of these middle ear pathologies with histopathologic changes of the tympanic membrane. The tympanic membrane pathologies included perforation, myringosclerosis, retraction, hemorrhage, fluid-filled cystic spaces, or dilated vessels. Temporal bones were also assessed for atelectasis. Fifty-six normal temporal bones were taken as controls for measurements. RESULTS: Significant correlations between tympanic membrane and middle ear pathology included myringosclerosis and granulation tissue, myringosclerosis and ossicular pathology, retraction and cholesterol granuloma, retraction and cholesteatoma, retraction and ossicular pathology, perforation and ossicular pathology, and hemorrhage and granulation tissue. Additive effects of some pathologies were also observed. Almost half the bones with middle ear pathology had no associated tympanic membrane pathology, whereas multiple pathologic changes in the tympanic membrane generally showed underlying multiple pathologic changes in the middle ear. CONCLUSION: When tympanic membrane pathology is detected otoscopically, its presence, alone or in combination, can be a strong indicator of underlying middle ear pathology. However, a normal-appearing tympanic membrane does not exclude the possibility of middle ear pathology. These findings suggest the need for other diagnostic tools such as multifrequency tympanometry and otoacoustic emissions to complement otoscopy for diagnosis of middle ear pathology, especially in a tympanic membrane that appears "normal."

Adolescent↗

Involvement of prostaglandins in inflammation induced by latex of Calotropis procera.

INTRODUCTION: The aerial parts of the plant Calotropis procera produce milky white latex that causes inflammation of the skin and mucous membranes. Prostaglandins are one of the mediators released in an inflammatory response following induction of cyclooxygenase (COX). In the present study, we have evaluated the role of prostaglandins in inflammatory response elicited by the latex of C. procera. METHODS: Aqueous extract of dried latex of C. procera was injected into the 6-day air-pouch in the rat. The inflammatory response was evaluated by studying the air-pouch fluid for its volume, protein and prostaglandin (PG) E2 concentrations, and leucocyte counts. The granulation tissue from the pouch was quantified and studied for COX-2 expression by reverse transcriptase-polymerase chain reaction. The inhibitory effect of celecoxib and dexamethasone was evaluated on the aforementioned parameters. RESULTS: Dried latex produced an inflammatory response that was maximum at 6 h. It was associated with the accumulation of protein-rich fluid, leucocytes and PGE2 production. It also resulted in granulation of the pouch cavity that was a maximum on day 3. COX-2 expression could be detected in the granulation tissue on day 1 and it increased progressively up to day 5. The anti-inflammatory drugs celecoxib and dexamethasone significantly attenuated the inflammatory response and inhibited COX-2 expression in granulation tissue. CONCLUSIONS: Latex of C. procera induces an inflammatory response characterized by an early exudative phase accompanied by PGE2 production and a late proliferative phase associated with COX-2 induction. Both the phases were effectively inhibited by COX-2 inhibitors.

Animals↗

Expression of perlecan proteoglycan in the infarct zone of mouse myocardial infarction.

Perlecan, a basal lamina proteoglycan, has been shown to interact with other extracellular matrix (ECM) components, especially type IV collagen, and is thus involved in ECM formation. Perlecan has also been postulated to promote growth factor-receptor interactions, including the binding of basic fibroblast growth factor (bFGF) to its receptor, and to enhance mitogenesis and angiogenesis. To test our hypothesis that perlecan is increased in the myocardial infarct zone, we examined perlecan expression after experimentally induced myocardial infarction in BALb/c mice by the methods of in situ hybridization, Northern blotting, and immunohistochemistry. In situ hybridization revealed mRNA signals for perlecan in the infarct marginal zone on day 2 and in the infarct interior zone around infarct granulation tissue on day 7. On day 14 the signals were observed at the center point of the infarct. The signals were detected in spindle-shaped mesenchymal cells (fibroblasts and myofibroblasts). Some surviving myocytes in the infarct marginal zone also showed positive signals. The sequential changes in the perlecan mRNA signal distribution paralleled those for type IV collagen mRNA. Northern blotting demonstrated increased expression of perlecan consistent with the observations of in situ hybridization. Immunopositive staining for perlecan was observed in the infarct zone around granulation tissue on day 7 and in the entire infarct zone on days 14-28. Immunostaining for bFGF was localized surrounding the infarct granulation tissue on day 7 and overlapped with perlecan immunostaining. The present results demonstrated the expression of perlecan by spindle-shaped mesenchymal cells (fibroblasts and myofibroblasts) and some surviving myocytes in the myocardial infarct, indicating the contribution of perlecan to the pathological course of myocardial infarction.

Animals↗

Recombinant hepatocyte growth factor accelerates cutaneous wound healing in a diabetic mouse model.

We examined effects of recombinant hepatocyte growth factor (HGF) on cutaneous wound healing, using a full-thickness cutaneous excision model in diabetic mice. Topical administration of HGF, as well as basic fibroblast growth factor (bFGF), promoted the rate of wound closure and re-epithelialization. Both HGF and bFGF enhanced expansion of the granulation tissue and stimulated neovascularization on day 7 postwounding, wherein the increase in microvessel density in HGF-treated wounds was higher than that in bFGF-treated wounds. Matrix metalloproteinases (MMP-2 and MMP-9) activities involved in cell migration, angiogenesis, and extracellular matrix (ECM) remodeling, were enhanced by HGF-treatment on day 7. On day 28 postwounding (later stages of wound healing), granulation tissue in bFGF-treated wounds remained to a greater extent than that seen in saline- and HGF-treated wounds. Likewise, bFGF- but not HGF-treatment stimulated DNA synthesis of fibroblasts in granulation tissue, suggesting that HGF stimulates wound healing with lesser degree of susceptibility to cutaneous scarring. We propose that supplement of HGF may be a potential therapeutic approach for treatment of cutaneous ulcer.

Animals↗