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PubMed1984

The role of histamine and serotonin in the inflammatory reaction in an experimental model of open wounds in the rat.

The role of histamine and serotonin in the inflammatory reaction in the granulation tissue of open wounds in the rat was studied. The model involved plastic chambers attached to the edges of two open circular full-thickness skin wounds. Five days post-wounding, agonists or antagonists were applied in one of the two chambers, the adjacent wound serving as control. Thereafter blood flow and albumin extravasation were measured. Application of histamine (100 microM) caused an increase in granulation tissue blood flow by 36%, but left albumin extravasation unaffected. Treatment with mepyramine (H1 antagonist, 20 microM), cimetidine (H2 antagonist, 20 microM) or methysergide (serotonin antagonist, 20 microM) did not influence the level of either blood flow or albumin extravasation. It is suggested that endogeneous histamine and serotonin play a minor role in the inflammatory process in the granulation tissue of this model of healing wounds.

Animals↗
PubMed1993

Laser-assisted enterocystoplasty in rats.

The employment of laser welds to anastomose bowel to bladder in urological surgery has never been described. Using rats, we compared laser-assisted enterocystoplasty (LAE) with conventional sutured enterocystoplasty (CSE). A "patch" ileocystoplasty was performed using distal ileum. Operative time, intraluminal bursting pressure and histologic changes were evaluated. Operative time was 38% less in the LAE (p < 0.001). No statistically significant differences in bursting pressure between LAE and CSE groups was demonstrated (p = 0.654) in rats sacrificed 2 weeks postoperatively. Histologic findings in the laser-assisted enterocystoplasties included early loose granulation tissue and later organization of the granulation tissue with significant collagen deposition. In our preliminary study, laser welding of bowel within the urinary stream was safe, efficacious and rapid and resulted in a mechanically comparable surgical outcome.

Anastomosis, Surgical↗
PubMedDate not supplied

Exchange and the mechanical properties of the skin: oncotic and hydrostatic forces control by blood supply and lymphatic drainage.

Unwounded healthy skin can survive several hours without oxygen. The rich blood supply of the skin is important for thermoregulation, mostly only above the waist. Why then, does the skin of even the big toe have a rich blood supply? That exchange requirements are more for fluid in support of turgor and that this process is essential for the mechanical properties of the skin is suggested. It is argued that the supposed richness of blood supply is not sufficient for wound healing, and thus a new organ, granulation tissue, has to be grown. However, granulation tissue is mechanically inappropriate for the protective mechanical function of the skin and must be completely removed before healing is complete.

Journal Article↗
PubMed2003

Severe bronchial synechia after removal of a long-standing bronchial foreign body: a case report to support control bronchoscopy.

The authors report the case of a child who had severe bronchial synechia of the left main bronchus after removal of a pistachio shell embedded in granulation tissue. Histology finding of the removed granulation tissue at initial bronchoscopy showed an Actinomyces bacterial invasion. It was decided not to treat this local contamination and to perform a control bronchoscopy to verify the disappearance of local bacterial invasion. The control bonchoscopy performed 4 weeks after the foreign body (FB) removal disclosed a large central left main bronchus synechia producing a 70% reduction of the lumen, although the child had become asymptomatic except for a slight residual cough. The resection of the synechia restored a normal bronchial lumen. The performance of a systematic control bronchoscopy after removal of long standing FB is discussed and recommended.

Actinomycosis↗
PubMed2005

The alpha-3 polypeptide chain of laminin 5: insight into wound healing responses from the study of genodermatoses.

Laminin 5 (kalinin/epiligrin/nicein) is an essential structural component of the dermal-epidermal junction, composed of three polypeptide subunits: laminin alpha3, beta3 and gamma2. Studies of the inherited skin fragility disorder junctional epidermolysis bullosa (JEB) have suggested that the major role of this heterotrimeric protein is to act as an adhesive ligand essential for binding the epidermis to the underlying dermis and thus maintaining the integrity of the skin. Protein interaction studies have shown that the C terminus of the alpha3 subunit binds to a range of integrin complexes depending on the motility status of keratinocytes. This allows laminin 5 to interact with either hemidesmosomes or the actin cytoskeleton. Recently we have reported that the absence of the N-terminal region of laminin alpha3a in laryngo-onchyo-cutaneous syndrome causes excessive granulation tissue production at wound sites. As granulation tissue production is also a problem in JEB, this implicates laminin 5 in control of this wound healing response.

Cell Adhesion Molecules↗
PubMed1984

A transparent chamber for the dorsal skin fold of athymic mice.

A transparent chamber designed for insertion in the dorsal skin fold of athymic mice is described. The chamber is based on ingrowth of a layer of granulation tissue from the surrounding subcutis of the animals. The thickness of the tissue layer in the chamber is accurately given by an exchangeable chamber component and the construction allows repetitive access to the tissue inside the chamber. A freely movable skin flap is prepared surgically on the back of the animals, and the chamber is inserted in this flap in a second operation about 2 weeks later. In the absence of air bubbles, infectious foci and excessive adipose tissue in the chamber, ingrowth of granulation tissue is completed 2-4 weeks after the insertion. When infections of the skin enclosing the chamber and atrophy of the skin flap are prevented, the functioning time of the transparent chamber is determined by the life span of the animals. In the present study the athymic mice remained healthy for 4-5 months after insertion of the chamber although they were kept under conventional conditions, but were given antimicrobial covering. Since athymic mice accept some human xenografts, both normal tissues and neoplasms, vital microscopical studies of such xenografts implanted into the chamber can be performed. Preliminary results of such studies on a human malignant melanoma are presented.

Animals↗
PubMed2002

Foreign-body-induced otitis media: a case report.

Unilateral ear discharge is one of the usual complaints of the patients who visited the otolaryngology clinics, especially those patients who suffered from external or middle ear disease. We present a 33-year-old female patient who suffered from persistent ear discharge of the left ear. The local findings showed a yellowish to greenish discharge and fetid odor from her left ear canal, occupied by a large amount of granulation tissue. Wide removal of the diseased granulation tissue and tympanoplasty were performed in the patient. Four pieces of cotton were found in the external auditory canal and middle ear cavity during the operation. For more than 2 years of follow-up at our clinic, the patient has had a dry ear and her hearing ability also improved. Foreign-body-induced otitis media in adults is very rare. Therefore, we present this rare case and review the reported literature so that the clinical symptoms and signs, imaging findings, clinical treatment, prognosis, and hearing change in foreign-body-induced otitis media may be recognized and understood.

Adult↗
PubMedDate not supplied

[The condition of the Eustachian tube and its influence on the middle ear].

Any functional disturbance in the auditory tube may be documented morphologically. We demonstrated in case of a block changes within the tubal mucosa and in the adjacent salivary glands. Complete obliteration of the lumen is a very rare instance caused only by severe trauma or as a possible result of heavy inflammatory damage to the mucosa. A lack of ventilation produces in the tympanic cleft a vacuum, followed by a typical effusion out of the altered mucosa. Anaerobic conditions favour hyper and metaplastic transformation of the epithelium. The clinical picture resembles the non-purulent, closed form of otitis, serous otitis media. The missing clearance makes the discharge within the tympanic cleft a great challenge to the mucosa. Granulation tissue proliferates, an enzyme production is initiated and phagocytes help to eliminate or to organize the middle ear content. The clinical picture corresponds to otitis media adhaesiva. If the auditory tube is blocked long enough, the healing result leads to the atelectatic tympanon caused by scare tissue, dystrophic calcification, fatty degeneration of granulation tissue, fibrocystic transformation of the mucosa. The ossicular chain, if not destroyed or interrupted, is fixed. A very dangerous condition is caused by retractionpockets within the ear drum membrane. They give rise to secondary acquired cholesteatoma. In the beginning of the whole process we see the nonfunctioning auditory tube, provoked by an infection. The development of the tubal tonsil and the perivascular aggregations of immunocompetent cells lead to the opinion, that the tube is an immunological not only a mechanical barrier against ascending infections. Favoured by antibiotic treatment the inflammation is localized by the body's own defence within the tympanic tube and causes the blockage, the loss of function, which influences heavily the middle ear and its lining.

Cholesteatoma↗
PubMed1995

Differentiation factors induce expression of muscle, fat, cartilage, and bone in a clone of mouse pluripotent mesenchymal stem cells.

Growth factors have been used experimentally to accelerate wound healing by increasing scar tissue formation at a wound site. These studies suggest that stimulation of fibroblastic differentiation and proliferation are essential components of adult tissue repair. Recent studies report the presence of mesenchymal stem cells within granulation tissue and as connective tissue-resident stem cells. This suggests that mesenchymal stem cells as well as fibroblasts may contribute to wound healing and repair. To determine the potential for mesenchymal stem cells to contribute to nonfibrogenic tissue repair, a clonal population of murine mesenchymal stem cells was examined with dexamethasone, a general differentiation agent, and muscle morphogenetic protein, a specific differentiation-inducing agent. Dexamethasone induced the expression of phenotypic markers for fat, cartilage, and bone in the stem cells. Muscle morphogenetic protein induced the expression of mRNAs for the muscle specific regulatory genes MyoD1 and myogenin in these cells. These results suggest that pluripotent mesenchymal stem cells within connective tissue compartments and granulation tissue have the potential to contribute to functional tissue restoration, rather than contributing solely to fibrogenic scar tissue formation during tissue repair.

Adipose Tissue↗
PubMed2000

Actinomycosis of dogs caused by Actinomyces hordeovulneris.

Actinomyces hordeovulneris was isolated from the lesions of chronic pyogranulomatous pleuritis and pericarditis of one of three dogs showing similar symptoms. The parietal pleura and the pericardium were thickened and covered with fine short threads of angiofibroblastic tissue. About 500-1000 ml of reddish purulent exudate in the thorax of all three dogs contained large numbers of rice-grain-sized, soft, yellowish-white granules ("sulphur granules"). These granules had a central core of branching filaments of gram-positive bacteria embedded in thick granulation tissue. The parietal pleura, the mediastinal pleura and the pericardium were infiltrated mainly with neutrophils, and to a lesser extent with lymphocytes and plasma cells. A small number of eosinophils and giant cells was also observed. Large numbers of pyogranulomas embedded in the granulation tissue were composed of a core of necrotized granulation tissue, mixed with clusters of gram-positive branching bacteria, surrounded by an area of intact and degenerating neutrophils and lymphocytes. Bacteria were detected in the lesions by Brown-Brenn staining and were isolated from one of the affected animals. The isolated bacteria were identified as A. hordeovulneris. This was the first isolation of A. hordeovulneris in Hungary.

Actinomyces↗
PubMed2000

Immunolocalization of tenascin-C, alpha9 integrin subunit, and alphavbeta6 integrin during wound healing in human oral mucosa.

Tenascin-C (TN-C) and its isoforms are multidomain extracellular matrix (ECM) proteins that are believed to be involved in the regulation of stromal-epithelial interactions. Some of the interactions between TN-C and cells are mediated by integrins. In this study we analyzed the expression of TN-C and its large molecular weight splice isoform (TN-C(L)) and the putative TN-C-binding alpha9 and alphavbeta6 integrins during human wound repair. In 3-day-old oral mucosal wounds, immunoreactivity for alpha9 integrin localized abundantly at the migrating basal wound epithelial cells. TN-C and TN-C(L) were localized in the matrix between and underneath alpha9-expressing epithelial cells. In parallel with gradual downregulation of alpha9 integrin immunoreactivity in 7-day and older wounds, the expression of alphavbeta6 integrin was temporarily induced. Integrin alphavbeta6 co-localized in the same area as TN-C and TN-C(L) immunoreactivity at the cell-cell contacts of the basal and suprabasal cell layers of the wound epithelium. During granulation tissue formation and reorganization from 7 to 28 days after wounding, TN-C and TN-C(L) were abundantly localized in the granulation tissue. The findings show that TN-C(L) is expressed under the migrating epithelial front and in the granulation tissue during matrix deposition in wound repair. Preferential localization of alpha9 integrin in migrating epithelial cells and of alphavbeta6 integrin in epithelium after wound closure suggests different functions for these integrins in wound repair.

Alternative Splicing↗
PubMed2006

[Clinical management of deep facial burn].

OBJECTIVE: To explore the better clinical methods for the management of deep facial burn with optimal quality. Methods Fifty-four patients with deep facial burns were enrolled in the study and were divided into delayed skin grafting group (n=48) and early escharectomy group (n=6). In delayed grafting group, after the erosion of new born granulation tissue to the basal layer with blade holder or with peel or eschar shaving method at 3 postburn weeks (PBW) according to the eschar separation and granulation growth status, the whole face of the patients were divided into 10 regions and were then covered by split thickness auto skin. The same treatment was performed on the patients in early escharectomy group at 1 PBW. Physical therapy and plastic surgery were applied after skin grafting, and the patients were followed up from 3 month to 11 years. The first operation time, postburn facial operation time, operation times to repair the whole face, blood content of Hb, the amount of blood transfusion and hemorrhage and the prognosis were compared between the two groups. RESULTS: There was no difference between the two groups in regards to the first operation time, the total operation times,blood concentration of Hb before and after operation,and the amount of blood transfusion during the operation (P > 0.05). The operation time in delayed grafting group (21.9 +/- 3.2) d was obviously later than that in early escharectomy group (12.6 +/- 1.3) d, (P < 0.05). And there was evidently less amount of hemorrhage during operation(98 +/- 52) ml/100 cm2 than that in early escharectomy group (331 +/- 121) ml/100 cm2 (P < 0.01). The facial appearance of the patients in delayed grafting group was plump with more elasticity and richer expression compared with those in early grafting group. There exhibited different degrees of microstomia and both eyebrow defect in both groups during and after 1 postoperative year. In addition, mild to moderate ectropion and hypertrophic scar on the conjunction of grafted skin could appear in 80% of these patients. These deformities might be corrected by several times of plastic surgery. CONCLUSION: Based on the principle of arranging skin grafts according to the cosmetic and functional area units, split thickness skin grafting can provide satisfactory results for the repair of deep burn injury involving whole face when the wounds were treated with eschar peeling, tangential excision, escharectomy, granulation tissue scaling, or early escharectomy. In comparison with early escharectomy, eschar peeling, tangential excision, escharectomy, or granulation tissue scaling can get better results with less bleeding, full and round facial appearance, more elasticity of grafted skin and richer facial expression appearance after the operation. Meanwhile, effective physical therapy and scheduled plastic surgery after skin grafting can also be very important in achieving cosmetic results in the repair and reconstruction of whole facial deep burn.

Adolescent↗
PubMed1999

Glucose-induced inhibition of angiogenesis in the rat sponge granuloma is prevented by aminoguanidine.

Angiogenesis and granulation tissue formation that occur following subcutaneous implantation of sponge implants in nondiabetic rats were inhibited by topical administration of D-glucose (22 mM). The healing impairment induced by glucose was analogous to healing failures associated with diabetes. Angiogenesis has been determined by measuring hemoglobin content in the implants, correlated with histological evidence of cellular infiltration and granulation tissue formation. The amount of hemoglobin detected in the glucose-treated implants was significantly lower (0.06+/-0.005 g/dl) than the amount in the controls that received glucose 5 mM (0.12+/-0.012 g/dl), saline (0.10+/-0.006 g/dl) or mannitol (0.086+/-0.007 g/dl). Parallel histological studies corroborated the biochemical findings. Daily intraperitoneal injection of aminoguanidine (AG, 50 mg/kg) prevented glucose-induced inhibition of neovascularization and cellular infiltration in the sponge granuloma. Our results show the direct inhibitory effect of high glucose in the development of granulation tissue and indicate that it may be associated with nonenzymatic glycation of key components of the healing process in the rat sponge granuloma.

Animals↗
PubMed1992

Behavior of postcapillary venule pericytes during postnatal angiogenesis.

Autogeneic bone marrow was implanted into an artificially created cavity in a segment of rat sciatic nerve, after removal of nerve fascicles, without damaging the epineurium or surrounding microcirculation. Under these conditions, the bone marrow induces capillary growth and forms granulation tissue from surrounding tissues, the behavior of pericytes being studied in the preformed (preexisting) postcapillary venules of the latter. Beginning 20 h after bone marrow implantation, the pericytes of the preexisting postcapillary venules hypertrophy, with shortening of their processes, prominent nucleoli, dispersal of ribosomes into their free form, fragmentation of basal lamina, and increased DNA synthesis. The number of contact surfaces between pericytes and endothelium is noticeably lower than in controls. Many pericytes are in mitosis. Cells with a shape transitional between pericytes and interstitial fibroblast-like cells appear. In some cases, Monastral Blue (MB) was used as a marker of the cells in preexisting venule walls of the graft bed. In the earlier stages of the experiment, the MB labelling is restricted to the cytoplasm of pericytes and endothelial cells of postcapillary venules, and to the macrophages that occur in the space between pericytes and endothelium. Furthermore, the marker continues to be observed, at a later stage, in some of the following cells: pericytes and endothelial cells of the newly formed vessels, macrophages migrating into the interstitium, transitional cells between pericytes and fibroblasts, and typical fibroblasts of the granulation tissue. The present study provides greater evidence that preformed microvasculature pericytes are substantially activated during postnatal angiogenesis and granulation tissue formation, suggesting that they may contribute to the origin of new pericytes and fibroblasts.

Aging↗
PubMed2000

Treatment of soft tissue defects in pediatric patients using the V.A.C. system.

Twenty-seven consecutive pediatric patients presenting to the orthopaedic surgery or plastic surgery services were reviewed after completion of wound care with the Vacuum Assisted Closure (V.A.C.) system. Each patient presented with complex soft tissue wounds requiring coverage procedures. Patients with acute wounds and wounds present after nonsuccessful attempts at surgical closure (dehisced incisions and failed flaps) were treated. All soft tissue defects healed without extensive coverage procedures using the V.A.C. system. In the majority of patients, use of the V.A.C. system produced a profuse bed of granulation tissue over all exposed bone, tendon, joint, and/or hardware, which could be covered with split thickness skin graft. Other patients were treated successfully with delayed primary closure, local flap advancement (one patient underwent a pedicled cross-leg flap), or by secondary intention. Use of the V.A.C. device is valuable in increasing the rate of granulation tissue formation and healing of extensive soft tissue injuries in pediatric patients. This vacuum system aids in the debridement of necrotic tissue and local soluble inflammatory mediators that may inhibit the proliferation of granulation tissue. These improvements in the local wound environment seem to accelerate wound healing compared with traditional methods. Before the development of the V.A.C. system, a minimum of nine patients within this group would have required free tissue transfer to obtain adequate coverage. The V.A.C. device seems to permit earlier coverage with local tissue or split-thickness skin grafting techniques, thereby decreasing the need for extensive microvascular tissue transfers in pediatric patients.

Adolescent↗
PubMed1992

Histologic evaluation of wound healing in experimental intestinal anastomoses: effects of antineoplastic agents.

Histologic evaluation of intestinal wound healing with and without cytostatics was performed in 36 rats. Variables were the relative position of the wound edges in mucosa and muscularis, necrosis, exudate, granulation tissue, granulocytes, macrophages, fibroblasts, restoration of the mucosal epithelium, and repair of the muscularis propria. The relative position of the wound edges in the mucosa and the muscularis in the initial phase of wound healing depended on technique but appeared to improve in the later phases of wound healing. It was not affected by the administration of antineoplastic agents; neither were muscularis repair, epithelial restoration of the mucosa, necrosis, nor exudate. Granulation tissue, fibroblasts and macrophages were present in maximal amounts after 7 days appearing later or showing this maximum at a different moment in time when antineoplastic agents were given. The processes of epithelial and muscularis repair were not influenced by the relative position of the wound edges. Granulation tissue, macrophages, and fibroblasts were the best parameters for measuring the histologic evolution of intestinal wound healing, and the effects of antineoplastic agents upon it.

Anastomosis, Surgical↗
PubMedDate not supplied

Fixation methods for implantable port chamber: comparative study using glue, self-stabilizing leg and suture fixations in rabbits.

OBJECTIVE: To evaluate the fixation strength and tissue reaction of the glue fixation and self-stabilizing leg fixation methods and to compare the results with those of the conventional tagging suture fixation method. MATERIALS AND METHODS: Twelve healthy rabbits were selected and three different methods of implanting the port chamber were employed on the back of each rabbit. A total of thirty six port chambers were implanted with these three different methods, viz. the glue fixation method using tissue adhesive, the self-stabilizing leg method using a self-expandable stabilizing leg, and the suture fixation method. The fixation strength and the gross and histopathologic changes of each fixation method were evaluated at three days, one week, two weeks and four weeks after port implantation. RESULTS: The glue fixation method showed a good fixation strength, which was similar to that of the tagging suture method (p = 0.3486). Five of the six ports (83%) implanted with the glue fixation method which were examined after two weeks showed cracks on the external surface, but this had no adverse effects on their function. A large amount of granulation tissue reaction was found at the bottom of the chamber (p = 0.0025). The fixation with the self-stabilizing leg showed relatively lower fixation strength (p = 0.0043), but no turning-over of the chamber occurred. The fixation strength improved with time after the first week, and minimal granulation tissue reaction was observed with this method. CONCLUSION: The glue fixation method exhibited equal fixation strength compared to the suture fixation, but showed cracking and a large amount of granulation tissue, whereas the fixation with a self-stabilizing leg showed weaker fixation strength.

Alloys↗
PubMed2002

Skin blood flow response in the rat model of wound healing: expression of vasoactive factors.

BACKGROUND: Although the microvascular blood flow response to wounding is predominantly vasodilation at skin sites with nutritive capillary perfusion (NUTR), there is a significant vasoconstrictive response at sites with high arteriovenous perfusion (AV). There may be a difference between NUTR and AV sites in the vasoactive factors which mediate the blood flow response to wounding. We measured the levels of mRNA expression of several potential mediators of the blood flow response to assess this possible difference. MATERIALS AND METHODS: We measured skin blood flow at wounds placed at the back, a NUTR site, and at the paw, an AV site, in 12 Wistar Kyoto rats. Measurements were performed at baseline and then at 7 days post wounding. There was a significant increase in blood flow at back wound sites, with a rise from 4.1 +/- 0.3 ml/min/100 g to 9.8 +/- 1.9 ml/min/100 g. At the undisturbed wound perimeter, outside the zone of granulation tissue, flow rose to 7.3 +/- 1.1 ml/min/100 g. At the paw wound site, Day 0 flow was 8.8 +/- 0.8 ml/min/100 g. At 7 days, there was a significant decrease in flow at wound center to 5.5 +/- 0.5 ml/min/100 g. We measured the levels of inducible nitric oxide synthetase (iNOS), endothelin, endothelin receptor, vascular endothelial growth factor (VEGF), and keratinocyte growth factor (KGF) gene mRNAs using reverse transcriptase PCR. RESULTS: There was a 10-fold increase in NOS mRNA in granulation tissue of both wounds on Day 7. There was a lesser but still substantial increase in the wound perimeter tissue. Levels of endothelin mRNA in the wound and wound perimeter were significantly lower at the paw than at the back. At baseline, the level of endothelin receptor B (ETrB) mRNA was greater at the back than at the paw. Wounding resulted in a substantial increase in EtrB mRNA levels in granulation tissue, reaching the same level at the back and paw wounds. There was also a substantial rise in EtrB mRNA levels at the paw wound perimeter, so that there was a reversal of the baseline condition, with paw levels actually surpassing the levels at the back perimeter. CONCLUSIONS: Thus, we have found significant changes in mediators both of vasoconstriction and vasodilation affecting the healing wound. These changes affect NUTR and AV sites in different ways. These results demonstrate the complexity of the regulatory processes controlling microvascular blood flow in wound healing.

Animals↗