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TAL-1 protein expression in vascular lesions.

The distribution of TAL-1 protein, an important vascular promoter in mice, has been examined immunohistochemically in a range of human vascular lesions and normal tissues. Formalin-fixed, paraffin-embedded vascular lesions including granulation tissue, haemangiomas, Kaposi's sarcomas, spindle cell haemangioendotheliomas, and angiosarcomas, were examined using a monoclonal antibody to recombinant TAL-1. Endothelial cells in all lesions gave positive immunostaining of variable intensity. Granulation tissue and spindle cell areas of the vascular tumours gave the strongest staining (nuclear and cytoplasmic). The better-differentiated endothelial cells within the tumours and resident well-formed vessels were less positive and some cells were in fact negative. The malignant endothelial cells in angiosarcomas showed less intense positive staining than KS cells. This study has shown TAL-1 protein expression in a range of reactive, benign, and malignant vascular lesions. Protein expression appears to be stronger in the spindle cell areas, perhaps reflecting greater expression in less-differentiated endothelial cells.

Adult↗

Growth hormone effects on wound healing in malnourished animals: a histological study.

Systemic growth hormone (GH) markedly improves celiotomy wound strength in protein malnourished (PM) animals. This study was undertaken to analyze the effect of GH as a basis for anatomically understanding. Adult female Spraque-Dawley rats were divided into normally nourished controls, PM and GH-treated PM groups. Protein malnutrition was achieved by feeding 5.5% protein restricted chow every other day for eight weeks before surgery. Controls were fed 23.4% protein chow. All animals were fed 23.4% protein chow postoperatively. Rat-GH was injected subcutaneously twice daily (1.0 mg/day) for three days prior to and five days after 5 cm midline celiotomy. Bursting strength of the wound was measured at 3, 6 and 14 days postoperatively. Histologic wound specimens (hematoxylin and eosin) were obtained from each group. Wound strength of malnourished rats was significantly less than that of normal controls at six days after operation (p < 0.001). With administration of growth hormone, the wound strength was significantly improved. Histologically, there was no difference between groups on day 3. On day 6 the normal control group showed a decrease in the early inflammatory cell infiltrate with concurrent development of granulation tissue and a dense proliferation of fibroblasts. The PM wound showed fatty infiltration, a very narrow band of poorly formed granulation tissue and a sparse fibroblastic proliferation. The GH-treated PM group showed a combination of histologic findings. Fatty infiltration, similar to that in malnourished non-treated animals, was still evident but there was also a dense proliferation of capillary channels and fibroblasts comparable to normal animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Treatment of ureteral obstructions with the Wallstent endoprosthesis: preliminary results.

PURPOSE: To evaluate the efficacy of the Wallstent endoprosthesis in the treatment of ureteral strictures. PATIENTS AND METHODS: Wallstents with diameters of 10 mm were placed across five malignant and six benign ureteral strictures in eight patients. All patients were believed to have poor surgical options, and their strictures were being maintained with catheter drainage. Ten lesions involved ureteroenteric anastomoses, and one malignancy involved the midureter. RESULTS: Three stents (two patients) across malignant disease remained patent until the time of patient death (3-5 months); the remaining two stents (one patient) became occluded within 1 month. Only one of six stents placed for benign disease remained patent at 11 months. All occlusions in benign strictures resulted from ingrowth of hyperplastic urothelium and granulation tissue. Complete obstruction was usually present only focally within the stent. The malignant occlusions were caused by tumor ingrowth and granulation tissue. No major complications were directly related to the stents, but two infections occurred. CONCLUSION: Wallstent endoprostheses are ineffective in providing long-term relief in patients with benign ureteroenteric strictures. Further evaluation of their role in malignant strictures is needed.

Adult↗

Ultrasonographic and histopathological findings in equine superficial digital flexor tendon injury.

The ultrasonographic and histopathological findings in 12 normal and 28 injured superficial digital flexor tendons, with lesions ranging in duration from 2 days to 15 months, were compared. A consistent relationship between the ultrasonographic and histological findings was demonstrated. The echogenicity of lesions, the distinctness of their delineation from the surrounding tissue, and the presence and arrangement of the linear echoes were useful features by which to assess the ultrasonograms. Acute lesions were anechoic, a complex mixture of anechoic and hypoechoic areas, or diffusely hypoechoic. These appearances represented haemorrhage, fibrolysis and early granulation tissue. Fibroplasia and granulation tissue produced well to moderately well defined hypoechoic lesions. Chronic fibrosis was characterised by heterogeneously echogenic areas which were poorly defined from the surrounding tissue and had irregularly-arranged linear echoes on longitudinal images. Intratendinous scar formation resulted in multiple hyperechoic foci. Extensive peritendinous lesions were readily apparent on ultrasonograms, but intertendinous adhesions were more difficult to assess, and produced ill-definition of the borders between the superficial and deep digital flexor tendons.

Animals↗

The possible use of amniotic membrane in chronic leg ulcers.

UNLABELLED: A trial of living amniotic membrane is suggested as a suitable dressing for certain indolent ulcers. The type of ulcer which is large and chronic both in rate of healing as well as time since onset is well known to everyone. After eliminating any venous defect, oedema, cellulitis, correction of stiff joints, anaemia, we are left with a local indolent problem. What is the ideal dressing? Comfortable or relieves pain; harmless to the tissues and encourages removal of slough; encourages vascularity of the granulation tissue. Method of application: Amnion is applied for five days prior to skin grafting. RESULTS: Better results in those ulcers which have a venous origin rather than arterial. In most cases a clean delicate layer of granulation tissue forms. Histopathology: biopsy of the ulcer base: before application of amnion - dense fibrous tissue, few thick-walled vessels; after application of amnion - more delicate connective tissue, numerous vessels, with thinner walls. The formation of an amnion bank: To facilitate the availability of living amnion. To investigate the possibility of an extract of amnion which would produce the same results as the membrane itself.

Bandages↗

Melatonin suppresses the pinealectomy-induced elevation of collagen content in a wound.

The pineal gland hormone was shown to be involved in the regulation of repair and connective tissue accumulation in a wound. The hypothesis that melatonin injection could reverse the pinealectomy-induced elevation of the collagen content in scar tissue was verified. The effect of various melatonin doses (3, 30 and 100 micrograms/100 g body wt) on soluble, insoluble and total collagen content in the granulation tissue of a wound was investigated. The collagen level was estimated in pinealectomized rats, as well as in pinealectomized animals treated with melatonin. Ivalon sponges inserted subcutaneously were applied as a wound model. After 4 weeks the collagen content was measured as a hydroxyproline concentration in the dry tissue of the wound. The results showed that melatonin at the dose of 30 micrograms/100 g body wt significantly decreased both total and insoluble collagen content in the wounded tissue (p < 0.05), but other doses were ineffective. Pinealectomy increased the total (p = 0.05) and insoluble collagen level (p < 0.05) in the granulation tissue. Melatonin suppressed pinealectomy-induced elevation of the total and insoluble collagen content in the wounds (p < 0.05). No influence of the pineal gland on the soluble collagen content was observed. The results showed that melatonin was involved in the inhibitory control of the collagen content.

Animals↗

[The use of cartilage and tissue adhesives for the treatment of surgical-stomatological diseases in old age].

The authors used lyophilized cartilage in plate, bar, chip or powder form in elderly patients. The transplant was also utilized in managing defects resulting from the removal of jaw cysts, bone tumours, etc. Furthermore, the authors treated bone defects of the anterior wall of the maxillary sinus and of the hard palate as well as oro-antral perforations, infected wounds of the soft tissues and inflammatory bone processes. The patients in question had been treated in the surgical service during the years 1959--1975. The authors observed in elderly patients pathological alterations of the capillaries, haemorrhagic tendency and impairment of the blood-clotting mechanism. Furthermore, they found that the granulation tissue was of poor quality. In these cases they used cartilaginous tissue in powder form which promotes the formation of granulation tissue well supplied with blood. In the patients mentioned, the authors also utilized surgical adhesive, namely after tooth extractions and in managing their complications.

Aged↗

Recombinant basic fibroblast growth factor stimulates wound healing in healing-impaired db/db mice.

The stimulatory effect of recombinant basic fibroblast growth factor (bFGF) on wound healing was assessed using healing-impaired (db/db) mice. Full-thickness wounds were made in female diabetic C57BL/KsJ db/db mice, and their normal (db/+) littermates with a punch biopsy instrument. Recombinant bFGF was applied locally to the open wound once a day. The mice were later killed and histological sections of the wounds were prepared. The degree of wound healing was evaluated using several histological parameters such as degree of reepithelialization, granulation tissue thickness, matrix density, number of infiltrated cells, and number of capillaries. Wounds from normal mice displayed good reepithelialization rates and granulation tissue formation, while wounds from db/db mice had poor responses, especially in the dermal parameters. Although the application of bFGF to wounds in the normal (db/+) mice had little effect, application of bFGF to wounds in db/db mice induced significant responses in all of the dermal parameters compared with nontreated db/db mice (p less than 0.001). In the presence of bFGF, these parameters approximated those observed in nontreated littermates. A minimum of 0.5 microgram bFGF in either single or multiple applications was required for a significant effect. bFGF that was either boiled or pretreated with neutralizing antibody had little stimulatory effect. Time-course experiments indicated that the granulation response in bFGF-treated mice peaked between 8 and 12 d, and decreased after 12 d, while matrix density continued to increase until the 18th day (p less than 0.05). The breaking strength of healed linear wounds in db/db mice was also decreased when compared with heterozygous littermates. This parameter was also improved by the administration of bFGF to the wounds (p less than 0.05).

Animals↗

Effects of amnion and live yeast cell derivative on second-intention healing in horses.

Equine amnion and live yeast cell derivative were evaluated as a biological dressing and as a topical wound medicament respectively, in the treatment of granulating wounds of the distal portion of the limbs of horses. Wounds measuring 2.5 x 2.5 cm were created on the dorsomedial aspect of the metacarpal and metatarsal region of all 4 limbs of 9 horses. Each wound was assigned randomly to 1 of 3 treatment groups: group C, treated with a nonadherent bandage as a control; group A, treated with amnion beneath a nonadherent bandage; and group L, treated with live yeast cell derivative beneath a nonadherent bandage. Rates of contraction and epithelialization were not significantly different among groups. Percentage of epithelialization for group A was significantly greater throughout the study than for the other groups. Number of days to complete healing was significantly less in group A and significantly greater in group L than in group C. Incidence and severity of exuberant granulation tissue were significantly less in group A than in the other 2 groups. Group L had more frequent and severe cases of exuberant granulation tissue than the other 2 groups.

Amnion↗

[Morphology of healed burns treated by different methods].

The dynamics of burn wound healing was studied on biopsies from the wound area in 30 patients treated by open methods (treatment under conditions of abacterial environment and in a cabinet with laminar air). Twenty patients were treated by applications on the wound of ointment bandages. Under the bandages, the crust formed on the burn surface was infiltrated with polymorphonuclear leukocytes. When patients with burns over 10-25% of the body surface were treated in abacterial environment, a thin dry crust developed on the burn wound surface with small accumulations of microflora in its external layers. The granulation tissue filling the wound after early necrectomy contains numerous vessels and cell elements. In extensive burns (35-50% of the body surface) the granulation tissue fills the wound cavity incompletely, as separate islets.

Bandages↗

Adipogenic healing in adult mice by implantation of hollow devices in muscle.

In mammals, wound healing is thought to result in the formation of scar tissue, with the exception of bony healing after fractures. Here we describe a previously unknown pattern of wound healing in which adipose rather than scar tissue is formed. Adipogenesis is normally confined to the embryo, although there are several experimental models for adipogenesis with highly specific dietary, cytokine, matrix, sex, or age requirements. The adipogenic healing described in this work provides a simple and reproducible experimental mouse model for adipogenesis without these limitations. Mice received intramuscular implants of nylon mesh material. Fibrinous material impregnated implants and within 4 weeks was replaced with highly vascular granulation tissue, typical of wound healing. Also consistent with wound healing was a reduction in vascularity of the newly formed tissue over time (P < 0.05). Lipoblasts were prevalent in granulation tissue, reaching a maximum in week 2 (P < 0.001) but falling to very low levels by week 9. These cells matured to adipocytes, with intermediate forms being seen. The identity of lipoblasts and adipocytes was confirmed by Oil Red O staining and electron microscopy. Control experiments confirmed that adipogenesis was independent of the materials used as well as of the sex and age of the animals. Rather, adipogenesis appeared to be due to replacement of fibrinous material in a space created within muscle. It is possible that adipogenic healing represents an adaptation for limiting the formation of restrictive scar tissues within muscle, and that this is the basis for the formation of traumatic lipomas in humans. Also, muscle tissue is replaced by adipose cells, seemingly derived from pluripotential satellite cells, in several degenerative muscle conditions, suggesting a role for adipogenic healing in these conditions.

Adipocytes↗

Cell-matrix and cell-cell contacts of myofibroblasts: role in connective tissue remodeling.

It is presently accepted that fibroblast/myofibroblast modulation represents a crucial step in granulation tissue contraction and in the production of the connective tissue deformations typical of fibrocontractive diseases. In addition to synthesizing extracellular matrix (ECM) components, myofibroblasts can develop tensile force through the neoformation of alpha-smooth muscle actin (alpha-SMA) containing cytoplasmic stress fibers. Tension has been shown to be a crucial regulator of connective tissue remodeling. In order to coordinate tension distribution within connective tissue, cell-matrix and cell-cell contacts appear essential. This review addresses the formation, molecular structure and function of such structures that are characterized by their association with intracytoplasmic actin filaments. Actin associated cell-matrix adhesions appear to provide the interface between ECM components and intracellular stress fibers, thus contributing to the transmission of force to the substrate and to the detection of stress level in the matrix. Cell-cell adherens junctions appear to synchronize myofibroblast contractile activity. Further studies investigating the functions of these structures will be important for the understanding of the mechanisms of granulation tissue evolution and for the planification of strategies in view of influencing connective tissue deformations.

Actins↗

Expression of cardiac angiotensin-converting enzyme after myocardial infarction.

AIM: To localize cardiac angiotensin-converting enzyme (ACE) during left ventricular repair after myocardial infarction (MI). METHODS: Cardiac ACE was examined by immunohistochemical staining using monoclonal and polyclonal antibodies against ACE 24 h, 1 wk, 2 wk, 3 wk, and 6 wk after coronary artery ligation in rats. Immunofluorescent double staining technique was applied to distinguish the cells which express ACE. RESULTS: ACE staining was confined to the endothelial cells and distributed in normal cardiac tissue in a gradient pattern along the vascular tree: present around the whole circle of arterial endothelium, present in about 20% of the capillaries, and absent in the veins. One week after MI, ACE expression was noted in the granulation tissue. Three weeks after MI, necrosis within the infarction was replaced by granulation tissue and fibrous tissue which showed strong over-expression of ACE. Six weeks after MI, the region with positive ACE staining regressed and the area with high collagen content on the endocardial side showed only weak ACE stain. Most of the ACE-positive cells in the ACE-over-expression-area were endothelial cells. A few macrophages seen in these regions were also ACE-positive. CONCLUSION: Cardiac ACE was over expressed during the process of tissue repair following MI, reaching a peak in 3 wk. Endothelial cells took the most part of ACE expression.

Animals↗

Orbital exenteration with spontaneous granulation.

Excision of the orbital contents by orbital exenteration is required in the treatment of some eyelid and orbital carcinomas. Allowing the orbit to heal spontaneously with granulation tissue has several advantages over the popular technique of lining the orbital walls with a split-thickness skin graft. The use of granulation tissue is simpler, since it avoids the needs for obtaining a skin graft, and the final result is cosmetically more acceptable, because a shallower cavity occurs compared with the skin graft technique. The main disadvantages are that it takes longer for the orbit to heal and dressing changes are required more frequently. The spontaneous granulation technique has provided excellent results in 12 patients with exenterated orbits.

Adenocarcinoma↗

Sulfur mustard-induced skin burns in weanling swine evaluated clinically and histopathologically.

Histopathological indicators and clinical observations were used to evaluate wound severity, depth and degree of healing on days 2 and 8 for full-skin-thickness sulfur-mustard (HD)-induced burns in weanling swine. Six female weanling swine were exposed for 2 h to 400 microl of HD at each of six dose sites on the hairless abdominal skin. Biopsy samples (8 mm) were taken from the periphery and from the center of the wound on day 2, and the wound was excised on day 8. Histopathological indicators evaluated were epidermal necrosis, follicular necrosis, dermal necrosis, vascular necrosis, depth of injury, ulceration (loss of epidermis), granulation tissue response, neovascularization, re-epithelialization (hyperplasia) and completeness of healing. Wounds were more severe from anterior to posterior. Histopathological assessment of epidermal ulceration and necrosis of epidermis, dermis, basal epithelium, adnexal structures and subcutaneous tissue were useful indicators of wound development on day 2. Granulation tissue response (observed as early as day 8) and re-epithelialization were good indicators of wound healing. Clinical evaluations were performed on day 2 prior to and after debriding, and on study day 8. Clinical observations on study day 2 were for wound size and for exudation, erythema, edema, necrosis and eschar. Clinical observations on study day 8 were for the previous parameters and for re-epithelialization, granulation and infection. Wound size and severity increased from anterior to posterior position. Size, exudation and edema were useful indicators of wound development. These histological and clinical observation parameters will be used in future experiments to compare various treatments for HD-induced burns.

Animals↗

Vascular and microvascular changes--key factors in the development of acetic acid-induced gastric ulcers in rats.

The present study examined the time sequence and histologic and ultrastructural features of the formation and evolution of experimental, acetic acid-induced gastric ulcerations in rats. One hundred percent acetic acid was applied to the gastric serosa of 140 fasted male Sprague-Dawley rats through a polyethylene tube for 30 s. Gastric mucosal changes were evaluated at 1, 5, 15, and 30 min, 1 and 3 h, and 1, 2, 3, 5, 8, and 11 days after acetic acid application by visual inspection, by quantitative and qualitative light microscopy, and by transmission electron microscopy. Following exposure to acetic acid, the earliest morphologic changes occurred at 1 min and consisted of dilatation of large submucosal veins and arteries and mucosal collecting venules. Five to 15 minutes after injury, thrombi developed in submucosal veins and collecting venules, leading to microvascular stasis and mucosal necrosis. By 3 h, necrotic masses started to detach. By 24-48 h, necrotic changes penetrated the submucosa. By 72 h, most ulcers underwent transition into a "chronic" stage characterized histologically by the presence of granulation tissue at the bottom, and the appearance of a transitional healing zone at the margins. By 5 days, an increased amount of granulation tissue was observed and the gastric glands in transitional zones at the ulcer margin displayed cystic dilatation. Based on this study, we conclude that a key feature of acetic acid-induced ulcer formation is the early vascular and microvascular injury, which precedes glandular cell necrosis.

Acetates↗

A comparative study of epithelialization of subcutaneous fascial flaps and muscle-only flaps in the oral cavity. A rabbit model.

Epithelialization of subcutaneous fascial flaps and muscle-only flaps used for reconstruction of the oral mucosa were studied in a rabbit model. Angiography was performed to help to design a subcutaneous cervical fascial flap and a cleidomastoid muscle-only flap. These flaps were transferred into a mucoperiosteal defect on the mandibular alveolus. The flaps were gradually infiltrated by acute inflammatory cells from the periphery and then replaced by granulation tissue originating from the oral mucosa. The epithelialization was by secondary intention. An epithelial tongue from the surrounding epithelium migrated onto the granulating flaps with eventual coverage after three weeks. After two months, the muscle-only flap was covered by a poorly organized epithelium, different from the highly uniform epithelium in the fascial flap. The granulation tissue which replaced the muscle-only flap matured to fibrous tissue, associated with severe contraction. This was characterized by dense regular collagen fibers, no elastic fibers, and few capillaries, while the fibrous tissue which replaced the fascial flap was characterized by random collagen and elastic fiber morphology and numerous dilated blood vessels, and was associated with mild contraction. This experiment supports the view that the different extracellular matrices of these flaps may play a role in epithelial configuration and contraction.

Animals↗