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Intratumoral distribution of tritiated fluorodeoxyglucose in breast carcinoma: I. Are inflammatory cells important?

UNLABELLED: To investigate the contribution of various tumor components to tumor [3H]FDG uptake, the size of proliferative cell and macrophage populations and the extent of necrosis, inflammatory infiltration and granulation tissue formation were evaluated in syngeneic rat mammary cancers (RMC) grown in immunocompetent rats, an animal tumor model that closely mimics human breast carcinoma. METHODS: Tissue components of breast cancers grown in female Lewis rats (n = 6) were identified histologically and immunohistochemically. Tracer uptake was studied by quantitative autoradiography 2 hr after an intravenous injection of 100 muCi [3H]FDG. RESULTS;: RMC tumors were glandular, with small foci of necrosis and were surrounded by a thin layer of granulation tissue. Tumors retained approximately 4% of the injected FDG dose (1.9 +/- 0.27 muCi/g). Macrophages numbered 0.5% of total cancer cells (1.2 +/- 1.0 of 246 +/- 77) and 18.0% +/- 3.9% of the nuclei of cancer cells were proliferating cell nuclear antigen (PCNA) positive (52 +/- 27 of 293 +/- 55). FDG uptake (in apparent disintegrations per minute per microgram of protein) in the cancer cell was 47.3 +/- 5.6, with the highest uptake in foci of high tumor cell density (82.1 +/- 6.3). Lower levels of FDG uptake were found in necrotic areas (19.8 +/- 22.9), granulation tissue (26.9 +/- 9.2) and areas of inflammatory infiltration (20.5 +/- 15.5). CONCLUSION: These data suggest that FDG-PET imaging of untreated breast cancer mainly reflects tracer uptake in cancer cells.

Animals↗

Factors affecting success of split-thickness skin grafts in the modern burn unit.

BACKGROUND: The use of early tangential excision or excision to fascia of burn wounds has led to the application of split-thickness skin grafts (STSGs) to a variety of graft beds, including dermis, granulation tissue, fat, and fascia. Because insufficient objective data are available on the effect of the graft bed on survival of an STSG, a 2-year review of success rates of STSGs on a variety of graft beds was completed. METHODS: The success rates of all 599 STSGs applied to dermis, granulation tissue, fat, and fascia in 233 consecutive burn patients (mean total body surface area [TBSA] burned, 14.5%) by one surgeon at a regional burn center over a 2-year period were reviewed. Data were analyzed to compare outcomes of STSGs on the graft beds listed and in low-risk versus high-risk groups of patients (TBSA burned < or = 35% and > 35%; age < or = 18 years and > 18 years; age < or = 55 years and > 55 years; and diabetes mellitus). One-way analysis of variance was used to compare results of STSGs on different graft beds, and tests were used to analyze differences in results of STSGs in low-risk versus high-risk groups (p < 0.05, significant). RESULTS: The mean success rate at 14 days for all 599 STSGs applied in the 233 patients was 90 +/- 22%. The success rate of STSG on the various surfaces ranged from 85% (fascia) to 93% (dermis; granulation), but the differences among the four graft beds were not significant. Total body surface area burned (> 35%), older age (> 55 years), and the presence of diabetes mellitus each had a significant impact on the percentage take of STSGs at 14 days after application. CONCLUSION: In the hands of an experienced burn surgeon, the recipient bed has no significant impact on the success rate of STSGs at 14 days postgrafting, except in those patients 18 years or younger, in which the mean STSG success rate was significantly greater on granulation tissue compared with fat. TBSA burned > 35%, age > 55 years, and the presence of diabetes mellitus continue to have an adverse impact on the success rate of STSGs at 14 days.

Adolescent↗

Upregulated expression of chemokines in herniated nucleus pulposus resorption.

STUDY DESIGN: Immunohistologic examination was performed on surgically removed samples of herniated nucleus pulposus. OBJECTIVES: To determine what cell types predominate in the granulation tissues of herniated nucleus pulposus, and to elucidate whether chemokines are involved in the resorption process of herniated nucleus pulposus. SUMMARY OF BACKGROUND DATA. The study population consisted of 30 patients suffering from herniated nucleus pulposus. Five macroscopically normal discs were obtained from spinal cord tumor and spinal cord injury managed with anterior discectomy (age range, 27-63 years) as a healthy control group. METHODS: Immunohistochemical analysis was used to analyze the expression of chemokines. RESULTS: A marked infiltration of macrophage and vascular proliferation was identified with a T lymphocyte infiltration of mild degree in the granulation tissues. This tendency was more prominent in the exposed group compared with the nonexposed group. Infiltrating macrophages, fibroblasts, and endothelial cells in the granulation tissues strongly expressed monocyte chemotactic protein-1 and macrophage inflammatory protein-1 alpha. Statistical analysis demonstrated that the exposed group was more abundant in Factor VIII, monocyte chemotactic protein-1, and macrophage inflammatory protein-1 alpha positive cells than the unexposed group. CONCLUSIONS: Inflammatory cells and their positivity for chemokines, such as monocyte chemotactic protein-1 and macrophage inflammatory protein-1 alpha, are associated with blood vessels. Chemokines, such as monocyte chemotactic protein-1 and macrophage inflammatory protein-1 alpha, were overexpressed in macrophages, fibroblasts, and endothelial cells, suggesting that these chemokines contribute to activation and recruitment of macrophages in a paracrine or autocrine fashion.

Adolescent↗

Critical role of endogenous thrombospondin-1 in preventing expansion of healing myocardial infarcts.

BACKGROUND: Matricellular proteins are extracellular matrix proteins that do not contribute directly to tissue integrity but are capable of modulating cell function. We hypothesized that the matricellular protein thrombospondin (TSP)-1, a potent inhibitor of angiogenesis and activator of transforming growth factor (TGF-beta), is induced in healing myocardial infarcts and plays a role in suppressing the postinfarction inflammatory response, inhibiting local angiogenesis, and limiting expansion of granulation tissue into the noninfarcted area. METHODS AND RESULTS: We used a canine and a murine model of reperfused infarction. TSP-1 mRNA was induced in canine infarcts after 1 hour of ischemia and 3 to 7 days of reperfusion. TSP-1 protein showed a strikingly selective localization in the extracellular matrix, microvascular endothelium, and a subset of mononuclear cells of the infarct border zone after 5 to 28 days of reperfusion. Isolated canine venous endothelial cells showed low-level constitutive expression of TSP-1 mRNA, which was markedly induced by TGF-beta, and basic fibroblast growth factor. Murine infarcts also had marked TSP-1 deposition in the border zone. Infarcted TSP-1-/- mice exhibited sustained upregulation of the chemokines monocyte chemoattractant protein-1, macrophage inflammatory protein-1alpha, and interferon-gamma-inducible protein-10/CXCL10 and the cytokines interleukin-1beta, interleukin-6, and TGF-beta, suggesting an enhanced and prolonged postinfarction inflammatory response. In addition, TSP-1-/- mice had markedly increased macrophage and myofibroblast density in infarcts and in remodeling noninfarcted myocardial areas neighboring the myocardial scar, suggesting expansion of granulation tissue formation into the noninfarcted territory. TSP-1-/- animals had more extensive postinfarction remodeling than wild-type mice, although infarct size was similar in both groups. CONCLUSIONS: The infarct border zone may be capable of modulating the healing process through its unique extracellular matrix content. The selective endogenous expression of TSP-1 in the infarct border zone may serve as a "barrier," limiting expansion of granulation tissue and protecting the noninfarcted myocardium from fibrotic remodeling.

Animals↗

Tracheobronchial metal stents: effects of covering a bronchial ostium in pigs.

RATIONALE AND OBJECTIVES: The purpose of this study was to examine the effects of placing a metal stent across a bronchial orifice. MATERIALS AND METHODS: Nine pigs were used as test subjects, because the right upper lobe bronchus comes directly off the trachea in these animals. One of three types of metal stents was placed into the trachea of each pig and covered the orifice of the right upper lobe bronchus. Follow-up studies were performed at 1 and 3 months to evaluate the right upper lobe for signs of bronchial obstruction, infection, and atelectasis. The animals were sacrificed at 3 months to study the histopathologic changes of the trachea and lungs. RESULTS: Two upper lobe bronchi remained patent; seven were obstructed by granulation tissue or plugs of mucus and inflammatory cells. Right upper lobe infiltration and atelectasis were seen in eight animals. Interestingly, radiographic opacities were also common in other lung segments. There was a tendency toward fewer and less extensive lung opacities at 3 months compared with that at 1 month. At histopathologic examination, areas of both acute and chronic pneumonia were found in the right upper lobe of all animals. The segment of trachea covered by the stent was lined with a thin layer of granulation tissue containing neutrophils, monocytes, and lymphocytes. The stent luminal surface was covered with columnar, cuboidal, and stratified squamous epithelium. Tracheal stenosis was seen in three animals because of excessive granulation tissue in two and a collapsed stent in one. CONCLUSION: Placement of metal stents in pig trachea covering the orifice of the right upper lobe bronchus resulted in retention of secretions and secondary infection in the right upper lobe and other distant lung segments.

Animals↗

Healing of skeletal muscle injury: an ultrastructural and immunohistochemical study.

The healing of gastrocnemius muscle injury induced with a spring-loaded hammer in rats was analysed ultrastructurally and immunohistochemically. The ends of the ruptured myofibers retracted, which resulted in a central blood filled cavity. Central zone (CZ) later becomes occupied by granulation tissue scar. CZ is surrounded by a zone where myofibers are necrotized and phagocytosed by days 2-3. Complete regeneration within the preserved basal lamina (BL) cylinders takes place in 5-7 days. The regeneration of myofibers across the scar follows a pattern different from that within BL cylinders. Thin, often branched, myotubes grow out of the BL cylinders into the granulation tissue, where they extend between fibroblasts and collagen fibrils, in general oriented parallel to the preserved myofibers. The extension of the regenerating myotube seems to take place primarily by local synthesis in the growth cone. Fusing myoblasts provide nuclei, mostly along the sides but also occasionally at the tip of myotubes. Some myoblasts seem to derive from undifferentiated cells in the granulation tissue. By three weeks only a few thin myotubes had extended across the gap between the stumps of the ruptured myofibers. Growing myotubes appear to attach to the surrounding connective tissue by specialized structures, an attachment which evidently transmits contraction force across the gap, allowing use of the injured limb before the healing is complete.

Animals↗

Histological characteristics of the healing process of frozen skin allograft used in the treatment of burns.

Combined transplantation of skin autograft and allograft was used for the treatment of severe burns. The allografts were obtained from cadavers and were pretreated with 15 per cent glycerol for 2 h at 4 degrees C then frozen at -80 degrees C until used. Patches of autografts were placed over the burns and were covered by a stretched mesh of allografts. Biopsy samples of transplanted skin were obtained from 5 days to 4 weeks after grafting. Sections were examined by histological and immunohistochemical strainings. At 4 days, the epidermal-dermal junction of allografted skin was separated due to migration of epithelial cells derived from autograft epidermis or from skin appendages of recipient dermis. At 2 weeks, dermal fibroblasts and capillaries proliferated in autografts. At 3 weeks, the dermal components of the allograft were covered by epithelial cells from recipient tissue and were invaded by fibroblasts and capillaries. At 4 weeks, allografted skin was replaced by granulation tissue, which mediated the adhesion of the grafts to the underlying tissue. Skin allografts with a freeze-thawing pretreatment provide an appropriate matrix for the epithelial relining and for the growth of granulation tissue in burned skin.

Adult↗

Isolation of silica-dependent protein from rat lung with special reference to development of fibrosis.

Silicosis was produced experimentally in rats by single intratracheal injections of various doses of SiO2 dust. The weight of the lungs as well as the contents of total nitrogen, collagen, nucleic acids (especially RNA), and lipids increased in accordance with the dose and the time interval. Fibrogenic stimulation in vitro was shown by the supernatant of the homogenized lung in the incorporation of proline into incubated granulation tissue or lung fibroblasts. The fibrogenic factor-activity depended more on the time interval after the injection than on the SiO2 dose. Electrophoresis of the soluble proteins in the silicotic rat lungs showed a protein of 16,000 Da, which was dependent on the time interval following SiO2 administration as well as on the dose itself, and which originated from macrophages. This protein was purified by repeated gel-filtration chromatography. It stimulated collagen synthesis in granulation-tissue cells at a concentration of about 10(-10) M in a dose-dependent way. It was acidic by amino acid composition but differed from calmodulin which also increased collagen synthesis in granulation-tissue cells in vitro. The ability of non-fractionated macrophage preparations to stimulate the incorporation of proline into collagen correlated inversely with the gross alkaline RNase activity.

Animals↗

Pleural mesothelioma of connective tissue type, localized fibrous tumour of the pleura, and reactive submesothelial hyperplasia. An immunohistochemical comparison.

Ten diffuse pleural mesotheliomas of connective tissue type have been compared with 14 examples of pleural granulation tissue and 7 localized fibrous tumours of the pleura, using immunohistochemistry to identify cytokeratins of low and high molecular weight and vimentin. Low molecular weight cytokeratin and vimentin were both detected in 8 of the 10 mesotheliomas and in 12 of the 14 reactive lesions. High molecular weight cytokeratin was rarely detected in either lesion. The seven localized fibrous tumours of the pleura were all positive for vimentin and negative for both cytokeratins. These findings support an origin of connective tissue type mesotheliomas from multipotential submesothelial spindle cells and of localized fibrous tumours of the pleura from either conventional fibroblasts or resting submesothelial spindle cells. Antibodies to cytokeratin help distinguish these two neoplasms but provide no assistance in the more difficult diagnostic problem of distinguishing mesotheliomas of connective tissue type from pleural reactions characterized by abundant granulation tissue.

Antibodies↗

Maggots and wound healing: an investigation of the effects of secretions from Lucilia sericata larvae upon interactions between human dermal fibroblasts and extracellular matrix components.

BACKGROUND: Through clinical observation, Lucilia sericata (greenbottle fly) larvae are credited with exerting the following beneficial effects upon a chronic nonhealing wound: removal of necrotic tissue ('debridement'), disinfection of the wound and active promotion of granulation tissue formation. As a major cellular component of granulation tissue, fibroblasts play an extensive role in healing. The composition of extracellular matrix (ECM) located in the wound is another important factor, partaking in a dynamic feedback loop with the fibroblasts that produce it. Fibroblast-ECM interactions therefore exert considerable influence upon new tissue formation. OBJECTIVES: To investigate the effects of L. sericata larval excretory/secretory products (ES) upon the behaviour of fibroblasts, seeded upon ECM component surfaces. METHODS: ES were collected by washing freshly hatched larvae in phosphate-buffered saline. Human dermal neonatal fibroblast cells were seeded upon fibronectin- or collagen-coated surfaces, together with untreated (or 'native') ES, heat-treated ES, or no ES (ES blank). Following incubation, fibroblast adhesion was determined using an adenosine triphosphate assay and, for confirmation, a total nucleic acid content assay. Cell spreading was observed using microscopy. The effect of ES upon fibronectin structure was observed using sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Peptide sequencing of suspected fibronectin fragments was performed using an 'electrospray' type time of flight mass spectrometer and 'Peptident' database search. RESULTS: ES significantly reduced fibroblast adhesion to both fibronectin and, to a lesser extent, collagen. Cell spreading was also reduced, yet cells remained viable. For both spreading and adhesion, heat-treated ES exerted significantly less activity than native, untreated ES. However, they still exhibited significant activity when compared with the ES blank. ES appeared to modify fibroblast adhesion indirectly via proteolytic fragmentation of the fibronectin protein surface. CONCLUSIONS: L. sericata larval secretions modify fibroblast adhesion and spreading across ECM protein surfaces, while keeping cells viable. Proteolytic activity of the ES played a significant role. If transferred to the wound situation, such alteration of fibroblast-ECM interactions may enhance new tissue formation.

Amino Acid Sequence↗

Electron microscopic changes in tropical endomyocardial fibrosis.

Electron microscopic examination of cardiac tissue from seven patients with tropical endomyocardial fibrosis showed the endocardium to be replaced by maturing granulation tissue containing haphazardly arranged collagen bundles, smooth muscle cells, blood vessels and degranulated mast cells. Mature collagen was present on the luminal aspect of the granulation tissue. Myofibres showed mitochondrial swelling, lamella bodies, focal myocytoplasmic clearing and collapsed intercalated discs. Small calibre blood vessels exhibited endothelial swelling, areas of basement membrane duplication and collections of neutrophilic and eosinophilic leucocytes. Eosinophils showed alteration in granule morphology. These changes are similar to the lesions reported in endomyocardial disease with eosinophilia.

Adolescent↗

Glomeruloid structures as vascular reaction in human gastrointestinal carcinoma.

Malignant tumors induce angiogenesis and modulation of microvasculature. Based on histologic and immunohistochemical analysis of human surgical material, we describe here the occurrence of glomeruloid structures in gastrointestinal carcinomas, and compare them with the microvasculature in inflammatory granulation tissue. The glomeruloid structures were composed of clusters of mutually fused capillaries with prominent swelling of endothelial cells and pericytes. They were thought to be specific for glioblastoma of the brain. The glomeruloid structures were observed juxtaposed to carcinoma nests in one-third of gastric carcinoma of intestinal type and colorectal carcinoma in the area of invasive growth beyond the muscularis mucosae. They were not observed in gastric carcinoma of diffuse type, intramucosal carcinoma, or inflammatory granulation tissue. The glomeruloid structures can be regarded as an extreme example of endothelial hyperplastic changes observed in cancer stroma. Our results suggested that glomeruloid structures can occur in carcinomas as vascular reaction, a mechanism different from that in inflammatory granulation tissues.

Actins↗

Accelerated wound healing in mice with a disruption of the thrombospondin 2 gene.

Mice that lack the extracellular matrix protein thrombospondin 2 have, among several abnormalities, an increase in vascular density, abnormal collagen fibrils, and dermal fibroblasts that are defective in adhesion. These findings suggested that responses involving these processes, such as wound healing, might be altered. To investigate the healing process, excisional wounds were made with the aid of a biopsy punch. Such wounds, observed over a 14 d period, appeared to heal at an accelerated rate and with less scarring in thrombospondin 2-null mice. Histologic analysis of thrombospondin 2-null wound sites revealed the presence of an irregularly organized and highly vascularized granulation tissue. In addition, thrombospondin 2-null wounds retained a higher total cellular content, than control wounds. No differences in wound re-epithelization rates were observed, but thrombospondin 2-null epithelia formed rete pegs and were thicker than control epithelia. By immunohistochemistry, we detected elevated levels and an irregular deposition pattern for fibronectin in thrombospondin 2-null wounds, observations that correlated with the abnormal collagen organization in the granulation tissue. Immunostaining for thrombospondin 2 in control wounds showed that the protein is present in both early and late wounds, in a scattered cell-associated pattern or widely distributed cell- and matrix-associated pattern, respectively. Our results suggest that thrombospondin 2 plays a crucial part in the organization and vascularization of the granulation tissue during healing, possibly by modulating fibroblast-matrix interactions in early wounds and regulating the extent of angiogenesis in late wounds.

Animals↗

Anti-inflammatory effect of proteinase inhibitors on carrageenin-induced inflammation in rats.

Proteinase inhibitors were evaluated for their anti-inflammatory actions on carrageenin-induced inflammation in rats. The development of granulation tissue and the exudate were markedly suppressed by a single injection of L-1-tosylamide-2-phenylethyl chloromethyl ketone (TPCK) into the carrageenin-air-pouch immediately after carrageenin injection, whereas a single injection of TPCK at 12 or 24 hr after carrageenin injection was less effective or slightly effective respectively. These results suggest that proteinase inhibitors exert their anti-inflammatory actions by interfering with the initial inflammatory reactions after carrageenin injection. When the wet weight of granulation tissue and the weight of exudate were measured on day 4 after the simultaneous injection of carrageenin and inhibitors, a single injection of serine- and thiol-proteinase inhibitors including TPCK, leupeptin, antipain, chymostatin and cystamine suppressed the development of granulation tissue, though EDTA and o-phenanthroline, metallo-proteinase inhibitors, were also effective at a high dose. Exudate was reduced by treatment with TPCK in a dose-dependent manner, while EDTA and o-phenanthroline were effective only at a high dose. On the other hand, the migration of polymorphonuclear leukocytes into the carrageenin-air-pouch (the inflammatory lesion) was markedly suppressed by TPCK and leupeptin, while a high dose of cystamine and o-phenanthroline was slightly effective, and antipain, chymostatin, pepstatin, elastatinal, EDTA, trans-1-aminomethylcyclohexane 4-carboxylic acid and aprotinin were without effect.

Animals↗

Accelerated healing of excisional skin wounds by PL 14736 in alloxan-hyperglycemic rats.

PL 14736 is a synthetic peptide, originally isolated from human gastric juice, that has anti-inflammatory and tissue-protective actions in experimental models of gastrointestinal inflammation. To investigate its possible benefit in poorly healing skin wounds, the effects of the topical application of PL 14736 in a gel formulation have been studied on full-thickness excisional wounds in rats, either healthy or made hyperglycemic by alloxan (175 mg/kg s.c.) 5 days previously. The effects of becaplermin gel (platelet-derived growth factor, PDGF-BB, Regranex, a standard therapy for diabetic foot ulcers, were investigated for comparison. Healing was evaluated for up to 7 days after wounding, using digital planimetry analysis, macroscopic scoring and histology. While healing was too rapid in healthy rats to observe enhancement by either treatment, in the hyperglycemic rats which exhibited delayed healing, PL 14736 (10-1,000 microg/wound) produced a dose-dependent acceleration of wound healing (determined by macroscopic scoring) equivalent at the highest doses to that observed with becaplermin. The beneficial effect on healing was associated with increased deposition of organized granulation tissue by day 7 for both PL 14736 and becaplermin, as determined histologically. PL 14736 tended to have a greater effect than becaplermin on the formation of granulation tissue containing mature collagen. Wound contraction, as measured by planimetry, was not significantly affected. In conclusion, topical PL 14736 produces a dose-dependent acceleration of deficient skin wound healing in hyperglycemic rats by facilitating granulation tissue formation, similar to the response seen with topical becaplermin, the standard therapy for diabetic skin wounds. PL 14736 may represent an alternative therapy for delayed wound healing, such as that seen with diabetic foot ulcers, without the proliferative concerns or immunogenicity associated with growth factors.

Alloxan↗

Autologous platelet-derived wound healing factor promotes angiogenesis via alphavbeta3-integrin expression in chronic wounds.

Healing of venous leg ulcers depends on the adhesive interaction and formation of new vascular cells. Angiogenesis on the surface of angiogenic blood vessels requires the vascular integrin alphavbeta3 also known as the vitronectin receptor. Autologous platelet-derived wound healing factor (autologous PDWHF) has been described to regulate the wound healing process by forming granulation tissue in the early healing phase. Here we analysed the influence of autologous PDWHF on the expression of the alphavbeta3 integrin in tissue specimen of venous leg ulcers in comparison with placebo treated controls by using reverse transcriptase-polymerase chain reaction and immunohistochemistry. Our investigations provide evidence that mRNA and protein expression of alphavbeta3 were significantly increased in healing venous leg ulcers after 96 h treatment (p<0.05), whereas the total amount of alphavbeta3 mRNA and protein was not altered in placebo treated patients. In healing leg ulcers the alphavbeta3 integrin was predominantly localized around capillary vessels preferentially at sites of newly formed granulation tissue. Placebo controlled patients displayed no altered expression of the alphavbeta3 integrin in biopsy specimen. These findings suggest that topical autologous platelet-derived wound healing factor influences the process of angiogenesis/revascularization via alphavbeta3 integrin-expression hereby promoting granulation tissue formation in healing leg ulcers.

Aged↗

Inflammatory reaction and collagen accumulation in an experimental model of open wounds in the rat. A comparison between gauze and Debrisan treatment.

Debrisan treatment was compared with the use of gauze in an experimental model of open wounds in the rat. The amounts of exudate absorbed by the gauze and by Debrisan were measured daily during the post-wounding period and the myeloperoxidase (MPO) activity in the exudate was determined. Blood flow, water content and accumulation of the collagen amino acid hydroxyproline in the granulation tissue were measured on days 3, 5, 7 and 10 post-wounding. The amount of exudate absorbed both by gauze and by Debrisan reached a peak on post-wounding days 4-5 and was greater in Debrisan-treated wounds. MPO activity in the Debrisan-absorbed exudate, on the other hand, was lower throughout the study period than in the exudate absorbed by gauze. Granulation tissue blood flow and water content reached maximum values on day 7 post-wounding, irrespective of treatment. Blood flows were 39% and 40% lower in the Debrisan-treated wounds on post-wound days 3 and 7, respectively, than in the gauze-treated wounds, whereas the water contents of the former wounds were 23% and 15% lower on days 3 and 10, respectively. The hydroxyproline content of the granulation tissue increased continuously from day 3 to day 10 and was similar in the two wounds. These results suggest that Debrisan is more effective than gauze for absorbing wound exudate, when applied on an openly secreting wound. In addition, the inflammatory reaction taking place in Debrisan-treated wounds seems to be less severe than in wounds treated with gauze.

Animals↗

Expression of MMP1 in surgical and radiation-impaired wound healing and its effects on the healing process.

Radiation-impaired wound is characterized by delayed healing, nonhealing, and carcinogenesis. The mechanism remains unclear. Matrix metalloproteinases (MMPs) are one family of key regulators of the process of wound healing. Their abnormal expression plays important roles in the formation of some chronic skin ulcers. The objective of this project was to study the expression of MMP1 in surgical and radiation-impaired wound healing and its effects on the healing process and tissue remodeling. A rat model of radiation-impaired wound healing was used. Routine light microscopy, electron microscopy, immunohistochemistry, and in situ hybridization, all of which enabled the detection of MMP1 expression during the healing process, were performed. The wound healing process was impaired and delayed. In rats receiving 25Gy gamma-ray locally, the irradiated wounds healed 6 days later than the nonirradiated controls. The following changes in MMP1 expression were found: (1) In the early inflammatory phase and in the period of granulation tissue formation, MMP1 expression was only slightly if at all affected in the newly formed epidermis of irradiated wounds compared with controls. Later, the epidermal expression of MMP1 in radiation wounds was comparatively increased following the delay of the healing process. (2) MMP1 expression in irradiated wounds was markedly decreased in fibroblasts, endothelial cells, and macrophages compared with controls. The expression phase was prolonged because of the delay of the healing process. The reduced expression of MMP1 in granulation tissue retards such important processes as cell migration, angiogenesis, and tissue remodeling, thus slowing the healing process. The expression ofMMP1 in the proliferating keratinocytes may help re-epithelialization. However, in the late healing period, overexpression of MMP1 in the epidermis may hinder the establishment of basal membrane and the formation of granulation tissue, and affect the tissue remodeling process.

Animals↗