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PubMed1997

Kinetics and collagenolytic role of eosinophils in chronic gastric ulcer in the rat.

An association between eosinophils and tissue damage has been observed in numerous disorders. However, few reports have addressed the role of infiltrating eosinophils in gastric ulcer healing. The aim of this study was to investigate the kinetics and role of eosinophils infiltrating experimental chronic gastric ulcers in the rat. We developed a monoclonal antibody against human matrix metalloproteinase 1 (MMP1) purified from conditioned culture medium of human skin fibroblasts. Acetic acid-induced gastric ulcers were resected from rats on days 1, 3, 5, 10, 20, 40, and 180 after the days of induction (day 0). Tissue specimens were immunostained with this antibody and examined with an electron microscope. Few eosinophils were observed in the granulation tissue until day 20. By days 40 and 180, MMP1-positive eosinophils had increased in the granulation tissue of open ulcers. Azan staining revealed dispersed collagen fibers around infiltrating eosinophils. In contrast, scars demonstrated few eosinophils in fibrous tissue on days 40 and 180. Eosinophils which express MMP1 infiltrate granulation tissue at the chronic stage of gastric ulceration. The results suggest that eosinophils may play a role in tissue remodeling and deterioration of ulceration.

Acetic Acid↗
PubMed2000

Migration of polyethylene wear debris in one type of uncemented femoral component with circumferential porous coating: an autopsy study of 5 femurs.

This autopsy study analyzed the migration of polyethylene wear debris adjacent to uncemented femoral components with circumferential porous coating. Five femoral specimens retrieved at autopsy from 3 patients were investigated. Two stems were 40% porous coated, 2 were 80% porous coated, and 1 was 100% porous coated. The implants' time in situ ranged from 53 to 132 months (average, 94.8 months). All patients were followed clinically and radiographically until death. Radiographically, 3 of the stems were bone ingrown with proximal bone loss, 1 stem was mainly fibrous encapsulated, and 1 stem was completely fibrous encapsulated. Histologic examination of bone adjacent to the middle and distal sections of the femoral implant revealed no polyethylene wear debris or granulation tissue in any of the specimens. In 2 bone-ingrown cases, a small number of polyethylene particles and small areas of granulation tissue were present at the proximal level. This granulation tissue, however, did not cause major osteolysis. The findings in this study imply that circumferential porous coating of cementless femoral components could prevent distal migration of polyethylene wear debris along the bone-implant interface in both bone-ingrown and fibrous-encapsulated femoral implants.

Aged↗
PubMed2001

A case of anaerobic abscessed hydroxyapatite orbital implants.

The purpose of this report is to document an unusual case of implant infection in a patient who had undergone enucleation and hydroxyapatite orbital implant surgery. A 32-year-old woman presented with chronic orbital discomfort and discharge following a history of hydroxyapatite orbital implant surgery at another hospital 4 years previous. She exhibited profuse discharge with a yellow, creamy color and marked conjunctival chemosis. Granulation tissue was noted on the central conjunctival surface. Following the removal of the conjunctival granulation tissue, a central 3x5 mm conjunctival dehiscence was present with exposure of the hydroxyapatite implant. A culture of purulent drainage emanating from the exposed implant showed a growth of Clostridium acetobutylicum. Removal of the orbital implant was done. The implant was noted to be filled with pus. This case suggests that anaerobic infection may be suspected when the granulation tissue is observed and a discharge with a foul odor is found.

Abscess↗
PubMed1951

Desoxycorticosterone acetate and wound healing.

The effect of desoxycorticosterone acetate (DCA) on the granulation tissue of healing and healed linear laparotomy wounds was studied in young adult male guinea pigs maintained on a complete diet and on a known intake of ascorbic acid. DCA induces the production of an excessive amount of granulation tissue, as evidenced by a relatively great number of fibroblasts and by a larger amount of ground substance. This effect was accompanied by a slight to moderate lag in the maturation process of both cellular and intercellular elements. These changes were observed when DCA administration was begun 5 days prior to operation, but were less obvious or absent if DCA was injected, beginning on the 5th or 10th postoperative day. The results indicate that the action of DCA on immature, proliferating connective tissue is marked, and is considerably less or absent when connective tissue elements have reached partial or almost complete maturity. The effect of DCA on connective tissue does not appear to rest on the basis of an altered nutritional status. Chemical and histochemical studies of the adrenals suggest that the action of DCA on connective tissue is probably mediated through a disturbance of adrenocortical function, namely an imbalance between hormones of the zona glomerulosa (excess of DCA) and those of the zona fasciculata (deficiency of glucocorticoids). The presence of changes in granulation tissue and the lack of them in mature resting connective tissue of DCA-treated guinea pigs confirm the view that a profound difference in the response mechanism exists between resting and actively proliferating connective tissue.

Adrenal Cortex Hormones↗
PubMed1992

Chronic ear pathology in a model of neonatal amniotic fluid ear inoculation.

Human histopathologic studies have demonstrated that amniotic fluid cellular contents, keratinized squamous epithelial cells and lanugo hair, induce an intense inflammatory reaction including granulation tissue in the neonatal temporal bone. To investigate this reaction over a prolonged period, an animal model was studied. An aliquot of sterilized autologous hair and keratinized epithelial cells was placed into 14 gerbil bullae; saline was used as a contralateral control. The animals were sacrificed at intervals up to 6 months and the temporal bones were studied by light microscopy. All animals demonstrated nonpurulent inflammatory changes on the experimental side including granulation tissue, osteoneogenesis, tympanosclerosis, and cholesteatoma; the control side demonstrated minimal middle ear changes. We conclude that in this model autologous keratinized tissue provokes a foreign body response similar to the granulation tissue observed in human infants and, further, that over a prolonged period the middle ear demonstrates more severe pathologic consequences.

Amniotic Fluid↗
PubMed2005

The pathogenesis of discogenic low back pain.

Discogenic low back pain is a common cause of disability, but its pathogenesis is poorly understood. We collected 19 specimens of lumbar intervertebral discs from 17 patients with discogenic low back pain during posterior lumbar interbody fusion, 12 from physiologically ageing discs and ten from normal control discs. We investigated the histological features and assessed the immunoreactive activity of neurofilament (NF200) and neuropeptides such as substance P (SP) and vasoactive-intestinal peptide (VIP) in the nerve fibres. The distinct histological characteristic of the painful disc was the formation of a zone of vascularised granulation tissue from the nucleus pulposus to the outer part of the annulus fibrosus along the edges of the fissures. SP-, NF- and VIP-immunoreactive nerve fibres in the painful discs were more extensive than in the control discs. Growth of nerves deep into the annulus fibrosus and nucleus pulposus was observed mainly along the zone of granulation tissue in the painful discs. This suggests that the zone of granulation tissue with extensive innervation along the tears in the posterior part of the painful disc may be responsible for causing the pain of discography and of discogenic low back pain.

Adult↗
PubMed1975

[Cathepsin D and the catabolic degradation of proteoglycans in granulomatous tissue].

Incubated in vitro at 37 degrees C, granulation tissues release glycosaminoglycans into the incubation medium. Such release is inhibited if pepstatine is present in the medium. From this result, it can be inferred that the protien moiety of the proteioglycans is degraded by cathepsin D. Therefore a role of this enzyme in granulation tissues appears, especially in the late reparative phase.

Animals↗
PubMed1995

Cellular and molecular mechanisms of gastric ulcer healing. Is the quality of mucosal scar affected by treatment?

BACKGROUND: Ulcer healing, i.e. the reconstruction of the mucosal architecture, is an active process of filling the mucosal defect with proliferating and migrating epithelial cells and connective tissue. METHODS: This article represents a summary of histologic and ultrastructural assessment of the cellular events occurring during healing of experimental gastric ulcer. RESULTS: Mucosa adjacent to the ulcer crater forms a 'healing' zone. The gastric glands in this zone dilate and the epithelial cells lining these glands de-differentiate, express epidermal growth factor receptor, and proliferate. The latter is the result of local activation of genes encoding for EGF and its receptors. At the ulcer margin, proliferating and dividing epithelial cells migrate onto the granulation tissue to cover (re-epithelialize) the ulcer and bud into granulation tissue to reconstruct glandular structures within the ulcer scar. Re-epithelialization and reconstruction of epithelial structures is under control of epidermal growth factor (EGF) and related peptides which are produced locally by regenerating cells. Under control of fibroblast growth factors, granulation connective tissue grows extensively supplying (a) microvessels for restoration of the microvascular network and (b) connective tissue cells for restoration of the lamina propria within the mucosal scar. The final outcome of the healing process reflects a dynamic interaction between the epithelial component for the 'healing' zone at the ulcer margin and the connective tissue component (including microvessels) originating from the granulation tissue. Depending on these interactions, mucosal scar can be of good quality (restoration close to normal) or poor quality. While a number of pharmacologic agents affect gastric ulcer healing, it is unknown whether these drugs affect the quality of mucosal architecture reconstruction. In previous studies, we demonstrated that sucralfate exerts a trophic effect on gastric mucosa and, compared with omeprazole, improves the quality of restored mucosal structures within the scar of healed gastric ulcers. In the most recent studies, we demonstrated that treatment with sucralfate activates genes for EGF, bFGF, and their receptors, significantly increasing (vs placebo and omeprazole) expression of EGF and its receptor in ulcerated gastric mucosa. CONCLUSION: Thus, the superior quality of ulcer healing by sucralfate (versus omeprazole) is most likely based on its capacity to induce and stimulate expression of EGF, bFGF, and their receptors.

Animals↗
PubMed2006

[Comparative study of the effects of Gypsum Fibrosum and Gypsum Fibrosum Preparatum in promoting granulation].

OBJECTIVE: To investigate the effects of Gypsum Fibrosum and Gypsum Fibrosum Preparatum in promoting granulation. METHODS: The wounds of muscle layer were produced in rats by using surgical operation. Two round wounds, with diameter about 1.5 cm, were cut at the depilatory area of two sides of the back of each rat, with an interval of 2 cm, deep to muscle layer, and the thickness of the knife wound of muscle layer was about 0.15 cm. Forty SD rats with the wounds were randomly divided into 4 groups: untreated group, beifuji-treated group, Gypsum Fibrosum-treated group and Gypsum Fibrosum Preparatum-treated group, with 10 rats in each group. Then the wounds were sprinkled with powders of Gypsum Fibrosum and Gypsum Fibrosum Preparatum, or sprayed with beifuji solution, respectively. The healing state of granulation tissues of the wounds was observed at the eighth and fourteenth day respectively. RESULTS: The number of fibroblasts, the number of capillary tubes and the area of capillary tubes in granulation tissue of wounds in the Gypsum Fibrosum Preparatum-treated group were significantly higher than those in the untreated group and Gypsum Fibrosum-treated group (P<0.01). There were no statistical differences between the Gypsum Fibrosum Preparatum-treated group and the beifuji-treated group. However, Gypsum Fibrosum-treated group showed no obvious differences compared to the untreated group (P>0.05). CONCLUSIONS: Gypsum Fibrosum Preparatum can accelerate the formation of collagenoblast and micrangium in wounds, and the proliferation of granulation tissues, thus promoting the skin wounds to healing. The effect of Gypsum Fibrosum is changed after being calcined, and Gypsum Fibrosum Preparatum has obvious effect in promoting granulation.

Calcium Sulfate↗
PubMed2000

Histological features of resolving acute, non-complicated phlegmonous appendicitis.

The histological features of resolving acute appendicitis are described. Formalin-fixed, paraffin-embedded appendices of 200 cases with acute, non-complicated phlegmonous appendicitis were reviewed. In 80 out of 200 cases, a histological picture characterized by a predominantly lymphocytic infiltrate of the subserosa and muscularis propria or the subserosa alone was found. In the affected muscularis propria, eosinophils were admixed with lymphocytes, and the cellular infiltrate showed a lesser degree than that of the classic phlegmonous appendicitis. A multifocal, rather than a diffuse pattern of infiltration was observed. Cases were divided into three groups. Group 1: appendices with the typical features of phlegmonous appendicitis: 120 cases, 60%. Group 2: appendices with a predominantly lymphocytic infiltrate in the muscularis propria, subserosa, or both, and no granulation tissue: 65 cases, 32.5%. Group 3: appendices with granulation tissue: 15 cases, 7.5%. Complicated appendicitis was excluded. Data on the duration of the clinical symptoms were derived from the clinical history. The differences between the mean duration time of groups 1 and 2, and of groups 2 and 3 were statistically significant. The findings support the contention that a mixed infiltrate of lymphocytes and eosinophils represents a regression phase of acute appendicitis.

Acute Disease↗
PubMed2002

Topical platelet-derived growth factor enhances wound closure in the absence of wound contraction: an experimental and clinical study.

The effects of platelet-derived growth factor (PDGF) on wound healing in animal and human models were investigated. Four 1-cm2 wounds were made on the dorsum of 3 rats. A 0.5-cm punch wound was made behind each ear of 4 patients. Half the wounds were treated daily with vehicle, controls, and the rest were treated with PDGF. Treated wounds closed faster than the controls (animals: 16 +/- 3.2 days vs. 17.8 +/- 2.17 days; p < 0.05) and (patients: 16 +/- 0.67 days vs. 19.5 +/- 0.33 days; p < 0.05). Biopsies were taken at day 20 for polarized light-Sirius red histological analysis. The granulation tissue of PDGF-treated wounds showed fine collagen fibers with weak birefringence, characteristic of immature granulation tissue, deposited throughout the healed wound site. Such a pattern indicates wound closure by reepithelialization and filling in with scar. Control wound biopsies showed a small area of immature granulation tissue surrounded by intact dermal thick collagen fibers with strong birefringence. Such a pattern indicates wound closure by wound contraction. This shows that PDGF enhances wound closure by reepithelialization and the prevention of wound contraction.

Animals↗
PubMed1998

Cyclosporine A delays wound healing and apoptosis and suppresses activin beta-A expression in rats.

Cyclosporine A is a powerful immunosuppressive agent which is widely used for the prevention of allograft rejection and for the treatment of autoimmune diseases. Clinical and experimental data show that it may also act on connective tissue. We investigated the influence of cyclosporine A on granulation tissue formation and wound healing. Using an in vitro approach, we followed the time course of rat dermal fibroblasts during wound repair. Granulation fibroblasts were compared to dermal fibroblasts flow cytometrically and by mRNA analysis with respect to the expression of procollagen alpha1(I), integrin beta1, interleukin-6, transforming growth factor beta1, keratinocyte growth factor and activin betaA. The most pronounced effect in cyclosporine-treated rats was the strong down-regulation of activin beta expression. In cryo-sections of granulation tissue from the same rats, the distribution and expression intensity of intercellular adhesion molecule and its receptors were investigated by immunohistology. Clearly, a time course was detectable. Tissue from CsA-treated animals showed a delay of three days compared to untreated animals. Apoptosis was also delayed in CsA-treated rats by around three days. Furthermore, we investigated the effect of CsA on the expression of collagen alpha1(I), fibronectin and matrix metalloprotease 1 genes in dermal fibroblasts from untreated donors. No changes in the mRNA steady state levels of these genes were revealed after direct addition of different doses of CsA to fibroblast cultures. Our data suggest that CsA may interfere with the complicated net of interactions between connective tissue and the immune system by down-regulation of the inflammatory phase by modulation of cytokines and a subsequent delay of tissue repair.

Activins↗
PubMed2004

Management of congenital tracheal stenosis.

OBJECTIVES: Congenital tracheal stenosis is a rare disease. Various methods for treatment exist but there is still much debate as to the appropriate surgical procedure. We present our surgical experiences of patch tracheoplasty and slide tracheoplasty as viable methods for the treatment of congenital tracheal stenosis. METHODS: From 1994 to 2002, 13 patients were diagnosed with congenital tracheal stenosis. Eight patients (7 symptomatic and 1 asymptomatic) had their stenosis corrected, three by means of pericardial patch tracheoplasty, four by slide tracheoplasty, and one by resection and anastomosis. Concomitant operations were performed on six patients to treat congenital cardiovascular disease. Five patients showing no significant symptoms did not undergo tracheal surgery and received only cardiac procedures. A retrospective review of the hospital course, complications, and long-term results was conducted. RESULTS: Among the patch tracheoplasty group, every patient suffered from granulation tissue formation. One patient died of respiratory acidosis and one was hospitalized due to recurrent granulation tissue, which required frequent bronchoscopy. The third patient from this group is free of all symptoms. Among the slide tracheoplasty group, one patient died of anastomosis disruption. The three remaining patients are alive and well. The one patient who received resection and anastomosis is alive without symptoms. CONCLUSIONS: Surgical repair of long-segment congenital tracheal stenosis exhibited high mortality and morbidity rates. Every patient that underwent pericardial patch tracheoplasty suffered from troublesome granulation tissue. As slide tracheoplasty provided relatively good results in the short and mid-term follow-up periods, it seems to be a preferred method for the treatment of long-segment congenital tracheal stenosis.

Female↗
PubMedDate not supplied

Early tracheostomal healing in rabbits with use of various tracheal incisions.

Various tracheal incisions (vertical, horizontal, or window) are used by surgeons for creation of a tracheostomy. The inflammatory response and healing varies with each incision and may contribute to complications such as tracheal stenosis. This study evaluates the effect of these tracheotomies on early stomal wound healing in a rabbit model. Male juvenile New Zealand rabbits underwent tracheotomy, with each animal randomized to the type of tracheal incision used (vertical, horizontal, or window). After recovery, they were killed on postoperative days 2, 4, 6, and 8, with tissue removed for histologic examination. Paraffin-embedded stomal sections were analyzed quantitatively for amounts of granulation tissue, fibrosis, and epithelization. Groups were compared statistically using chi-square, ANOVA, Spearman's rho, and Mann-Whitney U tests with p less than 0.05 considered significant. Fibrosis was significantly increased in the vertical and horizontal groups when compared with the window group. This increase was statistically significant between postoperative days 2 and 4 (p < 0.05). The amount of granulation tissue was only significantly increased in the window group, whereas no difference was seen in the rate at which epithelization occurred with the various incisions. Vertical and horizontal tracheal wounds have less granulation tissue formation and more fibrosis compared with window tracheotomies during initial wound healing. This could lead to a "safer" tracheostomy tract in the early postoperative period.

Journal Article↗
PubMed2004

Impact of aging on gene expression in a rat model of ischemic cutaneous wound healing.

BACKGROUND: Tissue ischemia and aging are independent features associated with the healing impairment of cutaneous wounds. However, the pathophysiology of these processes as they relate to impaired-healing wounds is poorly understood. MATERIALS AND METHODS: A single full-thickness biopsy wound was made on both ears of young (3-6 month) and aged (>24 month) Fisher rats. One ear was rendered ischemic by transection of the vasculature at the ear base, while the other ear served as an internal nonischemic control. Wounds were harvested from 3 to 7 days and were evaluated histologically for either granulation tissue formation and epithelialization. Total RNA from wounds harvested at postoperative day 7 was probed using a nylon-based cDNA array to assess global genetic expression alterations. RESULTS: Healing in the rat ear model is impaired by both ischemia and advanced age as measured by granulation tissue formation and wound epithelialization. Granulation tissue formation was affected to a greater degree by ischemia than age (-58% versus -21%, respectively) while epithelialization displayed an opposite response (-17% versus -53%, respectively). Global analysis of gene expression suggests that ischemia engenders a marked increase in genes displaying altered expression in aged animals compared to young animals. Importantly, all possible alterations in gene expression are found in samples from aged ischemic wounds, indicating that gene regulation is not simply depressed by advanced age. CONCLUSIONS: Wound epithelialization appears to be affected to a greater degree by advanced age than by ischemia. The results demonstrate the distinctive phenotype presented by the clinically relevant combination of age and ischemia in an in vivo model of cutaneous wound healing.

Aging↗
PubMed2002

Histological findings in coil-packed experimental aneurysms 3 months after embolization.

OBJECTIVE: Knowledge regarding tissue reactions within coil-packed aneurysms is poor. The purpose of this study was to analyze histological changes in a chronic experimental bifurcation aneurysm model that might explain the protective effect of Guglielmi detachable coils. METHODS: The aneurysms were produced by means of a venous graft pouch at a surgically created bifurcation of the carotid artery in the neck of rabbits. After 3 weeks, embolization with Guglielmi detachable coils was performed in the treatment group but not in the control group (seven rabbits each). At the time of embolization, six of seven treated aneurysms were completely occluded according to radiological criteria. Twelve weeks later, all aneurysms were explanted after final angiography. Histological examinations were performed with coils in situ. RESULTS: Six of seven embolized aneurysms demonstrated complete occlusion in final angiography. But gross pathology revealed that all specimens had differently sized open cavities between the coils. In only two cases, these spaces were very small and the aneurysmal sacs were filled with coils and tissue by more than 90%. Light microscopy demonstrated intraluminal granulation tissue and strong chronic inflammatory wall thickening with numerous foreign body cells at the interface between coils and tissue. Coils were partially incorporated into the aneurysmal wall, sometimes close to the surface and occasionally even outside the wall within the surrounding tissue. CONCLUSION: The protective effect of Guglielmi detachable coil treatment in our chronic experimental bifurcation aneurysms results from formation of intraluminal granulation tissue and wall thickening attributable to chronic inflammation.

Animals↗
PubMed2002

Differential expression and distribution of syndecan-1 and -2 in periodontal wound healing of the rat.

Cell-surface proteoglycans participate in several biological functions including interactions with adhesion molecules, growth factors and a variety of other effector molecules. Accordingly, these molecules play a central role in various aspects of cell-cell and cell-matrix interactions. To investigate the expression and distribution of the cell surface proteoglycans, syndecan-1 and -2, during periodontal wound healing, immunohistochemical analyses were carried out using monoclonal antibodies against syndecan-1, or -2 core proteins. Both syndecan-1 and -2 were expressed and distributed differentially at various stages of early inflammatory cell infiltration, granulation tissue formation, and tissue remodeling in periodontal wound healing. Expression of syndecan-1 was noted in inflammatory cells within and around the fibrin clots during the earliest stages of inflammatory cells infiltration. During granulation tissue formation it was noted in fibroblast-like cells and newly formed blood vessels. Syndecan-1 was not seen in newly formed bone or cementum matrix at any of the time periods studied. Syndecan-1 expression was generally less during the late stages of wound healing but was markedly expressed in cells that were close to the repairing junctional epithelium. In contrast, syndecan-2 expression and distribution was not evident at the early stages of inflammatory cell infiltration. During the formation of granulation tissue and subsequent tissue remodeling, syndecan-2 was expressed extracellularly in the newly formed fibrils which were oriented toward the root surface. Syndecan-2 was found to be significantly expressed on cells that were close to the root surface and within the matrix of repaired cementum covering root dentin as well as at the alveolar bone edge. These findings indicate that syndecan-1 and -2 may have distinctive functions during wound healing of the periodontium. The appearance of syndecan-1 may involve both cell-cell and cell-matrix interactions, while syndecan-2 showed a predilection to associate with cell-matrix interactions during hard tissue formation.

Alveolar Process↗
PubMed2002

Maxillary sinus augmentation model in rabbits: effect of occluded nasal ostium on new bone formation.

This study was undertaken to establish an experimental model for maxillary sinus augmentation in rabbits and to clarify the bone response to the occluded nasal ostium. In rabbits without ostial occlusion, the elevation of the sinus mucosa resulted in formation of a subantral hollow space filled with blood clots and granulation tissue 1 week after operation. The newly formed bone filled in the space had a central granulation tissue. The space was almost completely replaced by a normal sinus airspace after 3 weeks. In rabbits with ostial occlusion, a fully formed bone mass was seen after 3 weeks. The mass had both mature trabeculae and peripheral cortical bone containing no sinus airspace after 6 weeks. This animal model for maxillary sinus augmentation may improve our understanding of the bone formation procedure in humans and delineate how sinus air pressure caused by the occluded nasal ostium affects the quantity and fate of newly formed bone.

Air Pressure↗