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PubMed1981

Proteinase inhibitors suppress the formation of granulation tissue in the carrageenin-induced inflammation in rats.

Effect of proteinase inhibitors on the carrageenin-induced inflammation was studied. The formation of granulation tissue was markedly inhibited by a single injection of epsilon-amino-n-caproic acid n-hexyl ester (EACA hexyl ester, 300 mg/kg) into the carrageenin-airpouch immediately after carrageenin injection, whereas repeated injections of the inhibitor starting at 12 hr, 24 hr and 48 hr after carrageenin injection were less effective, slightly effective and ineffective, respectively. A dose-dependent inhibition of both the formation of granulation tissue and the migration of polymorphonuclear leukocytes (PMNs) into the inflammatory locus was found by a single injection of EACA hexyl ester into the carrageenin-airpouch immediately after carrageenin injection. Similarly, a single injection of L-1-tosylamide-2-phenylethyl chloromethyl ketone (TPCK, 50 mg/kg) and N-alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK, 30 mg/kg) inhibited both the formation of granulation tissue and the migration of PMNs into the inflammatory locus. These results suggest that serine proteinase inhibitors such as EACA hexyl ester, TPCK and TLCK exert their anti-inflammatory actions by interfering with the initial inflammatory reactions including the migration of PMNs into inflammatory locus after carrageenin injection.

Aminocaproic Acid↗
PubMed2001

[Intact-bridge tympanomastoidectomy procedure: a reasonable option in the surgery of chronic otitis media and mastoiditis with cholesteatoma and/or granulation tissue].

OBJECTIVE: To study and evaluate a surgical option for the treatment of otitis media and mastoiditis with cholesteatoma and/or granulation tissue. METHODS: The procedure is called intact-bridge tympanomastoidectomy (IBM). There are some modifications for the treatment of patients suffered from chronic otitis media and mastoiditis with cholesteatoma and/or granulation tissue. The features of IBM include: 1. the aditus, mastoid and attic opened and the intractable pathological tissues eradicated thoroughly. 2. the posterior tympanal space opened through the facial recess if necessary. 3. a widened middle ear space by lowering bony bridge established. 4. the adults blocked. 5. immediate or staging tympanoplasties conducted according to the conditions of mucosa in the tympanum. RESULTS: The modified IBM procedure was performed on 62 ears from 61 cases. The follow-up has been 12-38 months and more than two years in 51 ears. The dry ear was obtained within 5-13 weeks with an average of 6 weeks. In 24.2% of ears the air-bone gap(ABG) was 20dB HL or less and within 21-30 dB HL in 41.9% of ears, the ABG over 31 dB HL was 16.1%. CONCLUSION: Our results indicate that IBM procedure fulfills the desired purposes of both open- and close-cavity techniques, the thorough eradication of diseased tissue allow to get a dry ear and restoration of hearing. IBM, therefore, is a reasonable choice for the surgery of otitis media and mastoiditis with cholesteatoma and/or granulation tissue.

Adolescent↗
PubMed1983

Influence of local fibrin deposition on granulation tissue formation. A biochemical study in the rat.

A recently developed method for occlusion of fistulas with a fibrin clot initiated studies of the effects of deposited fibrin on granulation tissue formation. Perforated Teflon cylinders, empty or fibrin-filled, were implanted subcutaneously in rats for 2, 3 and 4 weeks and the composition of the ingrowing granulation tissue was followed by sequential biochemical analysis. The concentration of fat and water and the cellularity, measured as DNA concentration, were the same throughout the period studied in the granulation tissue from cylinders implanted empty and fibrin filled. After 2 weeks of implantation, the collagen concentration was higher in fibrin-filled cylinders than in cylinders implanted empty. The higher collagen concentration was explained by a higher proportion of mature collagen-synthesising cells. After 3 and 4 weeks of implantation there was no difference in the collagen concentration between cylinders implanted empty and fibrin filled.

Acid Phosphatase↗
PubMed1995

Granulation tissue removal in routine and minimally invasive procedures.

This article reviews the use of a new mechanical surgical instrument, the D'Granulator, designed to quickly and easily remove granulation tissue while maintaining a blood-free field during periodontal and endodontic surgical procedures. A technique for minimally invasive periodontal bone grafting is also given. This technique allows for minimization of soft-tissue trauma and the removal of granulation tissue from periodontal defects using a much smaller surgical incision than that used in standard bone graft techniques.

Bone Transplantation↗
PubMedDate not supplied

[Effect of parenteral administration of melatonin on the biochemical composition of the rat granulation tissue].

The influence of long term parenteral melatonin administration on the biochemical composition of granulation tissue of surgical wounds in rats during healing was investigated. Physiological solution and solutions containing various concentrations of melatonin were subcutaneously injected to the animals within 3 weeks. Control and injected animals were wounded. Samples of gramilation tissue were investigated on the 5-th and the 8-th day of healing. The contents of oxyprolin, uronic acids, hexosamines, total lipids and their fractions, fractional composition of glycosaminoglicans and proteins composition of salt extracts were determined in the se samples. Repeated injections during three weeks caused the changes in biochemical composition of researched samples which were characteristic for stressful reaction of connective tissue. The specific changes are most expressed at long term introduction of a physiological solution to animals. The introduction of melatonin during similar period cansed protective effect, partially defending biochemical composition of granulation tissue from changes, which were induced by stressful situation.

Animals↗
PubMedDate not supplied

Topical vanadate optimizes collagen organization within granulation tissue.

Systemic ingestion of vanadate, a nonspecific inhibitor of tyrosine phosphatases, doubles wound breaking strength, enhances the packing of collagen fibers, and prevents the appearance of myofibroblasts in granulation tissue. Will the local application of vanadate mimic the systemic effects? Pairs of polyvinyl alcohol sponges, each with a central reservoir and attached injection port, were subcutaneously implanted in rats. Daily, one implant received 0.2 ml of saline and the other received 0.2 ml of 0.03 mM vanadate in saline. On day 7, harvested sponges had equivalent wet weights. The vanadate-treated sponges had fibroblasts separated by connective tissue, with a more intense birefringence of the collagen fibers. Transmission electron microscopy showed collagen more uniformly packed in the vanadate treated sponges where collagen fibers were equally spaced and had equal diameters. By immunohistology, myofibroblasts, defined by the expression of alpha-smooth muscle actin within stress fibers, were absent in vanadate-treated granulation tissue. The expression of alpha-smooth muscle actin was restricted to smooth muscle cells of blood vessels. Controls had densely packed alpha-smooth muscle actin staining myofibroblasts, weak birefringence, and randomly spaced collagen fibers with irregular diameters. We conclude that the local application of vanadate prevents the appearance of myofibroblasts and optimizes the organization of collagen fibers in developing granulation tissue.

Administration, Topical↗
PubMed1996

Impairment of granulation tissue formation after menopause.

Formation of connective tissue is an essential step in the process of wound healing. After menopause an atrophy of connective tissues in skin, bone, and reproductive organs takes place. Using a dead-space wound healing model we measured collagen synthesis and deposition, and cell replication in the granulation tissue of 18 premenopausal and 23 peri- and postmenopausal women not receiving any hormonal therapy. In the postmenopausal group collagen synthesis and deposition and cell number in the granulation tissue were diminished. These results document the impairment of the granulation tissue formation after menopause.

Adult↗
PubMed1978

Effects of different cyclophosphamide treatment schedules on collagen and collagenolytic activity in granulation tissue.

Cyclophosphamide was injected intraperitoneally into rats in doses of 6 or 10 mg/kg/day. The controls had daily intraperitoneal injections of physiological saline. After 14 days of treatment, granulation tissue was produced by subcutaneous implantation of viscose cellulose sponges. The treatment with cyclophosphamide and physiological saline was continued in different sequences for a further one or two 14-day periods. The rats were killed 14 or 28 days after the sponge implantation. Cyclophosphamide caused a decrease in body weight, in the number of leucocytes, in granuloma dry weight and in the granuloma content of free OH-proline while the water percentage increased. Ten mg/kg/day of cyclophosphamide had a more pronounced effect than 6 mg/kg/day. The results are consistent with an inhibitory effect of cyclophosphamide on granuloma formation and on the degradation of collagen. Accordingly, measurements of collagenolytic activity in granulation tissue after culture in vitro suggested an inhibition of collagenolysis after cyclophosphamide treatment. No effect of pretreatment was observed, and the effect of cyclophosphamide was independent of whether cyclophosphamide was given during the early or late phase of granulation tissue production.

Animals↗
PubMed1999

Histologic evidence of foreign body granulation tissue and de novo lesions in patients with coronary stent restenosis.

OBJECTIVES: We examined the relative contributions of foreign body granulation and de novo lesions to neointimal hyperplasia in atherectomized specimens of restenosis after coronary stenting. BACKGROUND: Clinicopathological studies have suggested that smooth muscle cell (SMC) hyperplasia is the most likely cause of restenosis after coronary stenting. It is not yet fully understood how SMC hyperplasia occurs or how SMCs stimulation can lead to intimal hyperplasia. Although inflammation has been postulated to be a major contributor to restenosis after coronary stenting, there is a paucity of data on the relationsip between inflammation and subsequent neointimal formation in humans. Only in a porcine experimental model of stent restenosis, foreign body granulation tissue as a cause of inflammation in stent restenosis was reported. METHODS: Tissue specimens were retrieved by directional atherectomy from 11 patients in whom stent restenosis developed after percutaneous revascularization of coronary artery disease. For specimens preserved in 10% buffered formalin, analysis of cellular composition was performed quantitatively after cell-specific immunostaining, i.e. CD68, UCHL-1, HLA-DR, smooth muscle actin, vimentin, desmin, PCNA and TGF-beta. RESULTS: Five of the 11 patients showed granulation tissues 3-6 months after stent implantation, of whom 3 patients revealed foreign body multinucleated giant cells around the stent struts where PCNA- and vimentin-positive SMCs were demonstrated. Calcification and de novo lesions in medial and adventitial tissues were observed in 3 other patients, and fresh and/or organized thrombi were documented in 3 of the 11 patients. CONCLUSIONS: These findings support the notion that stent restenosis results from SMC hyperplasia and suggest that the foreign body granulation tissue against metals of the stents and de novo lesions could play an important role in chronic inflammation leading to intimal hyperplasia and subsequently to stent restenosis in some patients. Clinicians should thus consider whether a patient may be allergic to stent components with unknown reaction, e.g. haptens.

Aged↗
PubMed1996

Tumor necrosis factor-alpha inhibits collagen synthesis in human and rat granulation tissue fibroblasts.

The purpose of the study was to examine the effects of tumor necrosis factor-alpha (TNF-alpha) on collagen gene expression in rat and human granulation tissue fibroblast cultures. The cells were exposed to 0.1, 1, 10, or 100 ng/ml of TNF-alpha, and the rate of collagen synthesis was measured as synthesis of protein-bound 3H-hydroxy-proline. Total cellular RNA was isolated from fibroblasts, and measurements of specific cellular RNAs from fibroblasts were performed by Northern blot hybridizations using 32P-labeled cDNA probes. In cultures of rat granulation tissue fibroblasts TNF-alpha decreased 3H-hydroxyproline production to about 75% of that in controls and it also decreased pro alpha 1(I) and pro alpha 1(III) collagen mRNA levels, maximally to 33% and 23% of the control levels, respectively. In cultures of human granulation tissue fibroblasts a similar inhibiting effect in the production of collagen was seen. TNF-alpha decreased the production of 3H-hydroxyproline to 56% of the control value with a dose of 100 ng/ml also having an inhibiting effect on pro alpha 1(I) collagen mRNA levels of up to 43% of the control level. However, no effect was seen on pro alpha 1(III) collagen mRNA levels.

Animals↗
PubMed2004

[Evaluation of healing effect for simultaneously tympanoplasty in treating chronic suppurative otitis media with cholesteatoma and/or granulation tissue].

OBJECTIVE: This study was designed to discuss possibility and factors influencing healing effect for simultaneously tympanoplasty of chronic suppurative otitis media with cholesteatoma and/or granulation tissue. METHOD: For 52 cases with chronic suppurative otitis media with cholesteatoma (30 ears) and/or granulation tissue (22 ears), cleaning lesion with simultaneously tympanoplasty was surgical procedure, among them, 12 ears treated with single tympanoplasty, 40 ears treated with mastoidectomy and tympanoplasty. RESULT: All cases had dry ears without recurring cholesteatoma. Among them, hearing of 5 patients improved more than 30 dB, 9 ears improved from 20 to 29 dB, 31 ears improved from 10 to 19 dB and 7 ears improved less than 10 dB. Hearing of no cases reduced than that in preoperation. CONCLUSION: Simultaneously tympanoplasty would be carried out possible in treating chronic suppurative otitis media with cholesteatoma and/or granulation tissue. There were two important factors influencing hearing improvement, which concluded effective area of tympanic membrane concussion, activity of stapes and/or stapes footplate. The main cause for failure in hearing improvement would be eustachian tube obstruction.

Adolescent↗
PubMed1982

Stimulation of wound healing, using brain extract with fibroblast growth factor (FGF) activity. I. Quantitative and biochemical studies into formation of granulation tissue.

In rats with polyvinyl rings implanted under the dorsal skin, the formation of granulation tissue was found to be stimulated by application of brain extract with fibroblast growth factor (FGF) S3 activity which had been obtained from cattle. This stimulating effect on wound healing proved to depend on doses and was detectable in rats aged two and six months on the third and seventh postoperative days. The desired action could be induced only by repetitive administration of FGF S3 or by coupling of the latter to SYSpur-derm, a synthetic dermatoplastic material. More fractions with potential action upon formation of granulation tissue proved to be obtainable from further biochemical separation of FGF S3. One of such fractions was successfully concentrated to a potentiality by which one tenth of the normal dose yielded the same effect as the full dose. Hexosamine and hydroxyproline levels were measured, at the same time, and found to stimulate fibroblasts. The findings are discussed.

Animals↗
PubMed2005

Platelets can neutralize hydrogen peroxide in an acute toxicity model with cells involved in granulation tissue formation.

Platelets play a key role in the replacement of the blood clot with granulation tissue during the early steps of bone regeneration. We hypothesized that activated platelets can neutralize locally produced reactive oxygen species, thereby protecting cells involved in granulation tissue formation. The potential of platelet-released supernatant (PRS) to neutralize hydrogen peroxide (H(2)O(2)) was tested in an acute toxicity model with osteogenic, inflammatory, and endothelial cells. In the human fetal osteoblastic cell line 1.19 (hFOB), considerable morphological changes, cell shedding, and dysfunction of the respiratory chain were observed when cells were exposed to 3 mM H(2)O(2). Caspase-3 and poly-(ADP-ribose)-polymerase were not activated, suggesting that cell death occurred by necrosis. Preincubation of osteogenic cells, leukocytes, or endothelial cells with PRS decreased the acute toxicity of H(2)O(2). The capacity of platelets to release H(2)O(2)-detoxifying activity was retained for up to 72 h. Aminotriazole, an inhibitor of catalase, decreased the cytoprotective activity of PRS, whereas blocking of glutathione peroxidase by mercaptosuccinate had no effect. These results suggest that platelet-released catalase can rapidly neutralize cytotoxic amounts of H(2)O(2), a process that may play a role during the early stages of bone regeneration.

Blood Platelets↗
PubMed1980

Effect of defibrinogenation on collagen synthesis in granulation tissue. A study in the rabbit.

Collagen synthesis was studied in sponge-induced early granulation tissue from rabbits defibrinogenated by Arvin. Tissue slices were incubated in vitro with 14C-proline. The formation of 14C-hydroxyproline and the incorporation of 14C-proline into proteins was determined. The incorporation of proline into collagen and proteins was equally reduced after defibrinogenation. A possible explanation for this is a reduced number of active fibroblasts in granulation tissue formed during defibrinogenation.

Afibrinogenemia↗
PubMed1984

Stimulation of wound healing, using brain extract with fibroblast growth factor (FGF) activity. III. Electron microscopy, autoradiography, and ultrastructural autoradiography of granulation tissue.

A bovine brain fraction with FGF activity (fibroblast growth factor) increased the formation of granulation tissue of rats in an experimental wound healing model. It was characterised by intensified formation of new capillaries, stimulation of the synthesis function of fibroblasts and myofibroblasts, and proliferation of freshly developed granulation tissue. The results obtained from light microscopy and autoradiographic electron microscopy with 3H-thymidine suggested significant increase in the labelling of activated, undifferentiated endothelial cells in vascular sprouts and of differentiated endothelial cells in developed capillaries. FGF S3 appeared to speed up the differentiation of freshly formed endothelial cells. Also labelled were pericytes and other fibroblastoid cells, undifferentiated mesenchymal cells, juvenile undifferentiated fibroblasts, mature fibroblasts, myofibroblasts, and macrophages. Pericytes are presumed to be preferential precursors of myofibroblasts, on account of their occurrence in time and similar ultrastructural parameters. Close neighbourhood of lymphocytes and labelled fibroblasts gave rise to the assumption of specific effects, such as stimulation by lymphokines.

Animals↗
PubMedDate not supplied

[Changes in lipoxygenase activity in developing granulation tissue during aseptic wound healing in rats].

Activation of lipoxygenases was found during development of granulation tissue in full-layer skin wound simulated in 100 Wistar rats and studied by means of electron paramagnetic resonance and high pressure liquid chromatography. Maximal activation of lipoxygenases within 2 and 6 days corresponded to two phases of wound healing: inflammation phase and phase of fibroblast proliferation during formation of the granulation tissue.

Animals↗