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PubMed1997

Possible participation of cyclooxygenase-2 in the recurrence of allergic inflammation in rats.

In the recurrence of allergic inflammation in a rat air pouch model, pouch fluid volume, prostaglandin E2 concentration in the pouch fluid, leukocyte infiltration into the pouch fluid, and granulation tissue weight were markedly increased by the antigen challenge. To clarify the role of cyclooxygenase-2 in the recurrence of allergic inflammation, the time-course of changes in protein levels of cyclooxygenase-1 and cyclooxygenase-2 in the granulation tissue and in the infiltrated leukocytes was examined by Western blot analysis. It was shown that cyclooxygenase-1 levels in the granulation tissue and in the infiltrated leukocytes were not changed by the antigen challenge, but cyclooxygenase-2 levels were increased. Furthermore, treatment with the selective cyclooxygenase-2 inhibitor, NS-398 ([N-2(cyclohexyloxy-4-nitrophenyl]-methanesulfonamide), suppressed the recurrence of allergic inflammation as did the non-selective cyclooxygenase-1/cyclooxygenase-2 inhibitor, indomethacin. The steroidal anti-inflammatory drug, dexamethasone, inhibited the induction of cyclooxygenase-2, and suppressed the allergic inflammation. These findings strongly suggested that cyclooxygenase-2 induced by the antigen challenge plays a role in the recurrence of inflammation induced by the allergic mechanism.

Animals↗
PubMedDate not supplied

Surgical repair of nasopharyngeal stenosis in a cat using a stent.

An intraluminal stent was used to maintain patency of a recurrent nasopharyngeal stenosis (NPS) in a cat. The stenotic membrane within the nasopharynx was resected, and a 2-cm long, braided-wire endoprosthesis was placed as a stent. The patient was evaluated at one day, six weeks, 19 weeks, and 49 weeks following surgery. The cat tolerated the stent well. The 19-week recheck revealed granulation tissue partially obstructing the pharyngeal aspect of the stent which was subsequently surgically resected. Complications after excision of the granulation tissue included intermittent upper respiratory congestion and nasal discharge. The 49-week recheck showed no increased granulation tissue; however, upper respiratory congestion was still present. This particular stent, and its use as described in this paper, is recommended in cases of chronic recurrent NPS.

Animals↗
PubMed1986

Sex steroid dependency of diabetes-induced changes in polyol metabolism, vascular permeability, and collagen cross-linking.

The effects of castration on diabetes-induced increases in collagen cross-linking and vascular permeability and on polyol levels in new granulation tissue formed after induction of streptozocin (STZ) diabetes were examined in male Sprague-Dawley rats. New granulation tissue formation was induced by implanting sterile polyester fabric subcutaneously (s.c.) at the time of STZ injection 3 wk before assessment of vascular permeability and collagen cross-linking. Castration was performed 10 days before implanting the fabric. The characteristic increases in collagen cross-linking (manifested by decreased solubility in 0.5 M acetic acid) and in albumin permeation of the vasculature seen in intact diabetic rats were completely prevented by castration. Net collagen accumulation was not affected by diabetes or castration. Castration also markedly diminished diabetes-induced increases in tissue levels of sorbitol and completely prevented the decreases in tissue levels of myo-inositol and scyllo-inositol observed in intact diabetic rats, but had no effect on serum glucose levels, nonenzymatic glycosylation of plasma and granulation tissue proteins, or plasma somatomedin-C levels. The demonstration that castration prevents diabetes-induced increases in vascular permeability and collagen cross-linking as well as imbalances in tissue levels of sorbitol, myo-inositol, and scyllo-inositol in this model indicates that all of these changes are sex steroid-dependent phenomena. While the pathogenesis of these vascular permeability and collagen cross-linking changes is clearly multifactorial, these new findings: indicate that the role of sex steroids in the development of late complications of diabetes may be far more important than hitherto suspected, and suggest an explanation for the clinical observation that diabetic complications are uncommon in prepubertal diabetic subjects regardless of duration of diabetes.

Animals↗
PubMedDate not supplied

Quantitative and reproducible murine model of excisional wound healing.

The goal of animal wound healing models is to replicate human physiology and predict therapeutic outcomes. There is currently no model of wound healing in rodents that closely parallels human wound healing. Rodents are attractive candidates for wound healing studies because of their availability, low cost, and ease of handling. However, rodent models have been criticized because the major mechanism of wound closure is contraction, whereas in humans reepithelialization and granulation tissue formation are the major mechanisms involved. This article describes a novel model of wound healing in mice utilizing wound splinting that is accurate, reproducible, minimizes wound contraction, and allows wound healing to occur through the processes of granulation and reepithelialization. Our results show that splinted wounds have an increased amount of granulation tissue deposition as compared to controls, but the rate of reepithelialization is not affected. Thus, this model eliminates wound contraction and allows rodents' wounds to heal by epithelialization and granulation tissue formation. Given these analogies to human wound healing, we believe that this technique is a useful model for the study of wound healing mechanisms and for the evaluation of new therapeutic modalities.

Animals↗
PubMed1952

The pattern of tissue reactions to autologous and homologous musculofascial transplants.

Simultaneous autologous and homologous musculofascial transplants were made in New Zealand white rabbits. The basic pattern of degeneration and granulation tissue organization of both types of transplant was essentially identical. The superposition of two reactions in the framework of organizing granulation tissue served to distinguish homologous from autologous transplants. One reaction to homologous transplants was predominantly characterized by lymphocytic infiltration and the other by angeitis. The principal locus of these reactions was in the musculofascial zone of the transplant, and from this zone the reactions spread to a variable degree through the fascia into the overlying pannus of granulation tissue. When single homologous transplants were made, the lymphocytic and mild angeitic forms of reaction predominated, becoming conspicuous at the end of 2 weeks. When multiple successive homologous transplants were made from the same donor to the same recipient, acute angeitis with thrombosis supervened and the lymphocytic reaction failed to develop or persist. Multiple successive autologous transplants, on the other hand, did not influence the type or degree of reaction to autologous transplants in the same animal. There was no evidence that autologous transplants had any influence upon the sequence of reactions to homologous transplants or that the presence of homologous transplants influenced the nature of the reaction to autologous transplants in the same animal. Until better methods are developed, methods of bio-assay of the type described, though lacking in quantitative precision, offer the best means for further analysis of factors which govern the incompatibility of tissues of one animal for those of another animal of the same species.

Animals↗
PubMed1997

Histochemical demonstration of nitric oxide in herniated lumbar discs. A clinical and animal model study.

STUDY DESIGN: This study was designed to localize the cells that produce nitric oxide in a lumbar disc herniation by histochemical method, including in situ hybridization. OBJECTIVE: To clarify which cells in herniated lumbar discs produce nitric oxide. SUMMARY OF BACKGROUND DATA: It was reported that herniated lumbar intervertebral disc specimens in culture are capable of producing nitric oxide. METHODS: Surgical specimens from lumbar disc herniation were examined to determine nitric oxide synthase histologically using nicotinamide adenine dinucleotide phosphate diaphorase histochemistry. Allografts of intervertebral disc materials were placed on the epidural space at L6 level in the rat. Nitric oxide synthase was examined in the applied tissues using nicotinamide adenine dinucleotide phosphate diaphorase histochemistry and in situ hybridization histochemistry. RESULTS: Nicotinamide adenine dinucleotide phosphate diaphorase (nitric oxide synthase) positive cells were observed in 2 (40%) of 5 herniated disc materials in patients. The positive cells were mainly in granulation tissue around intervertebral disc materials. In animal models, nitric oxide synthase-positive cells were observed in all specimens at 1 and 2 weeks postoperatively. Newly formed vessels and small round cells in granulation tissue around the grafted intervertebral disc showed positive reaction. In situ hybridization demonstrated the expression of inducible isoform of nitric oxide synthase messenger RNA (mRNA) identical to small round cells around the applied intervertebral disc. CONCLUSION: Nitric oxide in a lumbar disc herniation is mainly produced by cells in granulation tissue around the herniated intervertebral disc.

Adult↗
PubMed1980

[The pathogenesis of spontaneous perirenal haematomas (author's transl)].

This report deals with two cases of a spontaneous perirenal hematoma. In the first case the spontaneous perirenal hematoma resulted from hemorrhages from the vessels of the stratum fibrovasculare of the renal capsule. This bleedings led to the development of a granulation tissue which in turn is rich in small blood vessels. Due to the lytic activities of this granulation tissue the hematomas became resorbed and finally are transformed into a big pseudocyst which surrounds the lower half of the kidney. On the other hand the new-built vessels of the granulation tissue are the source of further bleedings thereby perpetuating the process. In the second case the perirenal hematoma resulted from two aneurysms of the renal artery. In both cases clinical and radiological investigations had been unable to demonstrate the lesion.

Aneurysm↗
PubMed1976

Studies on cartilage formation XIX. Oxygen and glucose supply of the regenerating articular surface.

Complete removal of the articular cartilage in dogs is followed by regeneration of the articular surface. At the site of the bone wound, granulation tissue develops, which later differentiates into cartilage. The O2 and glucose supply of the regenerating articular surface is ensured by the synovial fluid, by the large exposed surface of the medullary cavity, and by the capillary network of the granulation tissue. Oxygen and glucose supply of the articular surface in different stages of differentiation has been statistically analyzed. It is suggested that in the early stage of regeneration O2 supply comes predominantly from the capillaries of the granulation tissue. Later on, as capillarization regresses, the oxygen supply, originating from the synovia and medullary cavity, assumes a more important role. In the stage of cartilage regeneration an oxygen-deficient state can be supposed in the entire articular surface, but areas differing in oxygen supply may be formed owing to local differences (due mainly to the extent of vascularization and degree of generation of the subchondral bone layer). At the site of chondrogenesis, conditions allowing aerobic metabolism of cells with reduced O2 requirements seem to be ensured. Glucose supply deriving from the above-mentioned sources satisfies the highest glucose requirements of the cells in the regenerating articular surface.

Animals↗
PubMed2002

Does coralline hydroxyapatite conduct fusion in instrumented posterior spine fusion?

OBJECTIVES: This study was conducted to investigate the course of incorporation of coralline hydroxyapatite in human spine. SUMMARY OF BACKGROUND DATA: Conventional techniques for surgical treatment of spine have a substantial failure rate and associated morbidity. Bone graft substitutes are an alternative technique to enhance fusion rates and limit the morbidity associated with spine fusion using autologous iliac crest bone graft. There are some experimental studies supporting the use of hydroxyapatite in spine surgery. MATERIAL & METHODS: During revision surgery specimens derived from the fusion mass from 15 operations in 13 patients, who received spinal instrumentation and fusion in cervical, thoracic, and lumbar spine and addition of coralline hydroxyapatite. The age of patients at the time of revision surgery was 46 +/- 20 years. The time lapsed from the implantation of coralline hydroxyapatite and revision surgery was 11 +/- 9 months. The indication for revision surgery was infection, pseudarthrosis, technical error, and pain related to bulky hardware. The diagnosis for the primary fusion was degenerative disease, trauma and scoliosis, and the material of instrumentation used was composed from titanium alloy. The coralline hydroxyapatite was applied on the decorticated posterior elements of the instrumented spine. Material from ten different places from the fusion mass was intraoperatively taken in all patients and was sent for histological evaluation using the Hematoxylin-eosin histological stain technique and photomicroscope. RESULTS: Under photomicroscope there was a remarkable concentration of foreign-body like giant cells & development of inflammatory granulation tissue around hydroxyapatite, which was gradually replaced by dense connective collagen tissue. Both inflammatory granulation and collagen tissue showed areas with foreign body reaction. In the cases, where bone has developed, the most initial finding was the presence of osteoblasts & apposition of osteoid in contact to hydroxyapatite granules. In a later phase, cancellous and lamellar bone has developed as a result of secondary ossification. Bone formation was observed in 11/15 cases and was related with the patient's age in favor of young patients (R=0.56, P<0.05), while there was no correlation with time lapsed from operation. CONCLUSION: Coralline hydroxyapatite conducts bone formation in spine surgery because in the vast majority of the operated cases for different spinal disorders bone and osteoid has developed around the implanted coralline hydroxyapatite.

Adolescent↗
PubMed1985

Cutaneous tissue repair: basic biologic considerations. I.

Wound repair of the integument is reviewed in the context of new developments in cell biology and biochemistry. Injury of the skin and concomitant blood vessel disruption lead to extravasation of blood constituents, followed by platelet aggregation and blood clotting. These events initiate inflammation and set the stage for repair processes. The macrophage plays a pivotal role in the transition between wound inflammation and repair (granulation tissue formation), since this cell both scavenges tissue debris and releases a plethora of biologically active substances that include growth factors. Although concrete evidence is lacking, growth factors are probably at least partially responsible for the angiogenesis and fibroplasia (granulation tissue) that gradually fill the wound void. If the epidermal barrier is disrupted during injury, reepithelialization begins within 24 hours and proceeds first over the margin of residual dermis and subsequently over granulation tissue. The signals for angiogenesis, fibroplasia, neomatrix formation, and reepithelialization in wound repair are not known, but a number of possibilities are discussed. Matrix remodeling is the last stage of wound repair and gradually increases the scar tensile strength to 70% to 80% of normal skin.

Animals↗
PubMed1997

Dynamic distribution of basic fibroblast growth factor during epulis formation: an immunohistochemical study in an enhanced healing process of the gingiva.

Basic fibroblast growth factor (bFGF) is thought to play an important role in wound healing. However, its histological localization, both in normal and pathological conditions in the oral mucosa, has not been well documented. We have studied the immunolocalization of bFGF in normal gingiva and gingival epulis specimens corresponding to different organizing stages. In normal gingiva, bFGF was detected in subpopulations of macrophages, mast cells and most endothelial cells in the lamina propria. Granulation tissue in epulides was histopathologically classified into six organizing stages. In stages 1 and 2, a small number of bFGF-positive macrophages was seen at the periphery of ulcer bases. In stages 3 and 4, histologically characterized by prominent capillary proliferation, large numbers of bFGF-positive macrophages and mast cells were located within granulation tissue. A positive reaction for bFGF was also found in some endothelial cells and in myxoedematous stroma that was rich in heparan sulfate proteoglycan. In stages 5 and 6, when fibrosis was accelerated, bFGF-positive macrophages and mast cells decreased in number and were localized only at the periphery of the fibrous tissue. These findings suggest that maximum amounts of bFGF are synthesized and released from some macrophages and mast cells into the extracellular matrix during neovascularization of granulation tissue.

Endothelium, Vascular↗
PubMed1999

[The reaction of regenerating connective tissue to acetylcholine in the dynamics of the denervation-reinnervation process].

The granulation tissue of wounds on upper surface of feet on the 7th day under repeated acetylcholine (Ach) application (0.02 g/1) was studied. In the control group, Ach-induced intensification of inflammatory process and bad condition of regenerating tissue of skin. This pathological reaction increased (fastly appeared ulceration) at once after crushing of right sciatic nerve in the denervated wound. It was less pathological in the contralateral (innervated) wounds. The effect of ACh was positive on later term of neurodystrophic process in the denervated wound and in the contralateral one. Cholinoceptive of granulation tissue of bilateral wound became normal after reinnervation.

Acetylcholine↗
PubMed1998

Ultrastructure of blood vessel regression in involution of foreign-body granuloma.

The diversity of endothelial cell deletion in regressing blood vessels during involution of granulation tissue was investigated in foreign-body granulomas induced by a collagen sponge implanted into the dorsum of the rat. Small blood vessel density counts were performed to determine the degree of blood vessel regression in the involution of granulation tissue in foreign-body granuloma. The density of these small blood vessels significantly decreased between 100 and 130 days after sponge implantation. The detachment of endothelial cells from their underlying basement membrane and the consequent protrusion into and/or out of the lumen in the vascular network of granulation tissue was observed by electron microscopy. Based on the pattern of manifestation in the endothelium and the characteristic deformation of nuclei, the detached endothelial cells were classified into two groups: 1) the endothelial cell apoptosis group and 2) the endothelial cell degeneration group. The essential difference between the two groups was easily distinguishable as the nucleus of the former group displayed chromatin condensation and margination as the hallmark of early apoptotic changes, while the nucleus of the latter group displayed a pinch structure and intranuclear pocket formation. However, the process by which the detached endothelial cells were shed into the vascular lumen and eventually eliminated from circulation was the same in both groups. The occurrence of both groups increased on the 90th day after sponge implantation and reached a maximum on the 110th day, indicating that the appearance of the groups was synchronized. These results suggest that the two major processes of apoptosis and degeneration of endothelial cells occur during endothelial cell deletion as a mechanism contributing to blood vessel regression.

Animals↗
PubMed1996

Acceleration of wound healing in diabetic mice by basic fibroblast growth factor.

We studied the effect of recombinant human basic fibroblast growth factor (bFGF) on wound healing in genetically diabetic mice. Wound closure after full-thickness excision of skin was markedly delayed in diabetic mice compared to normoglycemic mice. A single application of bFGF caused a marked acceleration of wound healing in a dose-dependent manner. There were no hypertrophic scars or unlimited granulation tissue formation in regenerated tissues treated with any doses of bFGF under histological examination. The repeated application of bFGF for 7 d showed a bell-shaped dose-response in the rate of wound closure, and the optimal dose was as small as 0.2-2 mu g per wound. Reduced angiogenesis and granulation tissue formation were observed in diabetic mice compared to normal mice, and bFGF treatment restored both responses to significant levels. The beneficial effect of bFGF on wound healing would be largely explained by enhanced angiogenesis and granulation tissue formation.

Animals↗
PubMedDate not supplied

Effect of growth factors on the characteristics of cells associated with equine wound healing and sarcoid formation.

Wound healing in equidae is delayed and more complicated than in other species. These complications arise from a condition known as exuberant granulation tissue formation. The lower limb of the horse is frequently slower to heal than other parts of the body and has a particular tendency to produce excess (exuberant) granulation tissue. Sarcoids are tumor-like lesions of the skin which often appear at the site of wounds. This study compared the growth characteristics of the sarcoid and granulation tissue-derived cells with normal dermal fibroblasts grown from primary cell cultures. All three cell types had distinct morphologic differences. Growth rate studies showed that the sarcoid and granulation tissue-derived cells grew at a slower rate than the normal cells. The addition of the growth factors epidermal growth factor, acidic fibroblast growth factor, and basic fibroblast growth factor selectively stimulated the replication of normal and sarcoid-derived cells but inhibited the growth of granulation tissue-derived cells. In contrast, transforming growth factor-beta was not preferentially inhibitory for the granulation tissue-derived cells. The addition of growth factors to the medium also produced distinct alterations in the morphology of the cells.

Journal Article↗
PubMed2000

Spatial and temporal expression of basic fibroblast growth factor protein during wound healing of rat skin.

BACKGROUND: Basic fibroblast growth factor (bFGF) stimulates the mitogenesis of various cells and plays a key part in wound healing. OBJECTIVES: To determine the spatial and temporal expression of bFGF protein during wound healing after burning of rat skin. METHODS: Immunohistochemical methods were used. RESULTS: The immunostaining for bFGF in the normal epidermis was faint and sporadic in the basal cell layer. However, significant staining for bFGF was found in four locations: regenerated epidermis, a band-like zone near the regenerated epidermis, renewed capillaries, and cells infiltrating into the granulation tissue at the inflammatory to proliferative stages after the burn. The intensity of immunostaining of regenerated epidermis, the band-like zone and renewed capillaries was maximal during the proliferative stage and decreased to normal levels or disappeared simultaneously with wound closure. Immunopositive macrophage-like cell numbers in the granulation tissue increased during the proliferative stage and promptly decreased after wound closure, but such cells were only poorly visible in the scar tissue until 42 days postburn. CONCLUSIONS: bFGF may affect the proliferation, differentiation and migration of regenerated keratinocytes and the recruitment of inflammatory cells, as well as neovascularization in granulation tissue during wound healing. Macrophages may play a pivotal role in cutaneous wound repair by producing bFGF not only during the inflammatory or proliferative stages but also during the remodelling stage.

Animals↗
PubMed1997

Experimental study of epithelialization of the muscle-only flap in the oral cavity.

PURPOSE: The purpose of this study was to observe the epithelialization process of the muscle-only flap used for reconstruction of the oral mucosal defects. MATERIALS AND METHODS: Forty-three male adult Japanese rabbits were used. A superiorly based cleidomastoid muscle flap was designed after vascular assessment. The flap was transferred into the oral cavity to cover a mucoperiosteal defect made in the mandibular alveolus. Epithelialization of the flap was histologically evaluated at designated intervals. RESULTS: The flaps survived without ischemic necrosis. By 8 days postoperation, the flap was infiltrated by acute inflammatory cells and being replaced by granulation tissue originating from the adjacent tissues. The oral epithelial cells advanced onto this granulating muscle flap, with eventual coverage by 21 days. The granulation tissue matured to fibrous tissue with significant contraction by 2 months. At 6 months postoperation, abnormally hyperkeratinized epithelium was seen on the flap. This differed from the surrounding parakeratinized oral epithelium. CONCLUSIONS: The muscle-only flap in the oral cavity epithelializes after the granulation process.

Actins↗