Basic fibroblast growth factor and epidermal growth factor reverse impaired ulcer healing of the rabbit oral mucosa

BACKGROUND: The therapies for refractory ulcers on the oral mucosa are symptomatic and very unsatisfactory. We hypothesized that application of growth factors might be able to achieve successful remission of the lesion. We evaluated the effects of systemic administration and topical application of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) on impaired wound healing of ulcers in the rabbit gingiva. METHODS: Almost uniform round ulcers could be created on the gingiva of the rabbits by chemical injury with acetic acid. When the submandibular glands were removed or i.v. injection of cisplatin (CDDP) and peplomycin sulfate was performed before ulcer formation, healing of the ulcers took longer than in untreated rabbits. To ascertain whether or not human EGF and bFGF affect rabbit cells, we first examined the effects of EGF and bFGF on the proliferation of the cells derived from rabbit gingiva. We then applied EGF or bFGF in these impaired healing models. RESULTS: EGF and bFGF promoted proliferation of the fibroblasts, and EGF also promoted proliferation of the keratinocytes isolated from gingival tissue of rabbits in vitro. Systemic injections of EGF and bFGF in rabbits, which had their submandibular glands removed, and topical application of bFGF accelerated healing of ulcers created in rabbits injected with CDDP and peplomycin sulfate. The ability of bFGF to promote the healing of ulcers was much greater than that of EGF. CONCLUSION: Basic FGF may be effective for refractory oral mucosal lesions.     

Regulation of fibroblast-induced collagen gel contraction by interleukin-1β

Fibroblasts incorporated within collagen gels induce a cell-mediated contraction of the gel to form a three-dimensional, tissue-like structure by a mechanism thought to mimic wound contraction in vivo . In this study a gel contraction model was used to investigate the ability of fibroblasts derived from adult gingiva, adult skin and fetal skin to organise a collagen matrix. In addition the effects of interleukin-1β (IL-1β) on the contraction process was also investigated. Over the concentration range 5-50 U/ml, IL-1β induced a statistically significant inhibition of gel contraction in all fibroblast cell types ( P <0.05), although fetal fibroblasts appeared least responsive and gingival fibroblasts most responsive to the inhibitory effects of this cytokine. Comparison of gel contraction by the different fibroblast strains indicated that fetal and gingival fibroblasts shared similar contraction kinetics. For the adult skin fibroblasts, three of five strains studied showed significantly diminished levels of gel contraction compared to fetal and gingival cells. This apparent difference in fibroblast phenotype may, at least in part, explain the fetal-like wound healing pattern seen in the oral mucosa.     

Monitoring pressure ulcer healing in persons with disabilities.

Pressure ulcers are a high-risk, high-volume, and high-cost problem for persons with disabilities. This article describes four tools published in the literature and reports the validity, reliability, strengths, and limitations of each. These tools include the Pressure Ulcer Scale for Healing (PUSH), the Pressure Sore Status Tool (PSST), the Sussman Wound Healing Tool (SWHT), and the Sessing Scale. Rehabilitation nurses should use a consistent framework with accurate quantification to assess, document, and monitor changes in pressure ulcers over time. Such a measurement tool must prove valid for the disabled population in which the tool is used. This will enable healthcare providers to communicate more effectively and evaluate the therapeutic plan of care.     

Periradicular healing in response to Diaket root-end filling material with and without tricalcium phosphate

The healing of the periradicular tissues was evaluated when the polyvinyl resin Diaket with and without tricalcium phosphate was used as surgical root-end filling material. Non-surgical root canal treatment was performed on 56 mandibular premolar roots in mongrel dogs. Following root-end resection, root-end cavity preparations were filled with Diaket, the comparative material, or Diaket in combination with tricalcium phosphate, the experimental material. Postsurgically, healing of the tissues adjacent to the filling materials and in the surrounding surgical site were evaluated at 30 and 60 days. There was virtually no statistically significant difference between the experimental and comparative group at or within the 30- or 60-day period with regard to inflammation, connective tissue formation, root-end encapsulation, cementum formation, or bone apposition. Findings suggest that cementogenesis occurred over both materials. The overall healing of the periradicular tissues was favourable.     

Mucosal features and granulocyte–monocyte-apheresis in steroid-dependent/refractory ulcerative colitis

BACKGROUND: Mucosa-infiltrated granulocyte neutrophils are an early characteristic of inflammation and the main histological feature of active ulcerative colitis. Mucosal healing has recently been indicated as an important tool in the evaluation of response to treatment. While several studies have stressed the efficacy of granulocyte-monocyte-apheresis in inducing clinical remission in active ulcerative colitis, few data are available on mucosal features. AIM: Aim of this study was to assess the effects of granulocyte-monocyte-apheresis on clinical and mucosal features in patients with ulcerative colitis, dependent upon or refractory to steroids. MATERIAL AND METHODS: From April 2004 to April 2005, 12 patients (5 females, 7 males, mean age 49 years, range 33-71 years), with mild-moderate ulcerative colitis (six left colitis, six pancolitis) dependent/refractory upon steroids were enrolled. Each patient was treated for a 5-week period with five cycles of granulocyte-monocyte-apheresis. Patients were evaluated at baseline and 1 week after the last apheresis by means of Global Physician Assessment, quality of life features, laboratory tests (erythrocyte sedimentation rate, CRP, full blood count, faecal calprotectine), endoscopy and histology. RESULTS: At week 6 of follow-up, complete mucosal healing was observed in 3 out of 12 patients, partial mucosal healing in 8 patients and no change in 1 patient. Clinical response was complete in 8 out of 12 patients. CONCLUSIONS: These data suggest that granulocyte-monocyte-apheresis induces an improvement both in clinical and mucosal lesions in steroid-dependent/refractory ulcerative colitis. Of note, the reduction in granulocyte infiltration and the improvement in mucosal lesions are accompanied by a reduction in faecal calprotectine.     

Microarray analysis of healing rat Achilles tendon: evidence for glutamate signaling mechanisms and embryonic gene expression in healing tendon tissue.

Tendon healing is a complex process consisting of a large number of intricate pathways roughly divided into the phases of inflammation, proliferation, and remodeling. Although these processes have been extensively studied at a variety of levels in recent years, there is still much that remains unknown. This study used microarray analyses to investigate the process at a genetic level in healing rat Achilles tendon at 1, 7, and 21 days postinjury, roughly representing the inflammation, proliferation, and remodeling phases. An interesting temporal expression profile was demonstrated, identifying both known and novel genes and pathways involved in the progression of tendon healing. Both inflammatory response and pro-proliferative genes were shown to be significantly upregulated from 24 h postinjury through to 21 days. Day 7 showed the largest increase in genetic activity, particularly with the expression of collagens and other extracellular matrix genes. Interestingly, there was also evidence of central nervous system-like glutamate-based signaling machinery present in tendon cells, as has recently been shown in bone. This type of signaling mechanism has not previously been shown to exist in tendon. Another novel finding from these analyses is that there appears to be several genes upregulated during healing which have exclusively or primarily been characterized as key modulators of proliferation and patterning during embryonic development. This may suggest that similar pathways are employed in wound healing as in the tightly regulated progression of growth and development in the embryo. These results could be of use in designing novel gene-based therapies to increase the efficacy and efficiency of tendon healing.     

Incisional healing in rats treated with diethyl maleate

Diethyl maleate (DEM) which binds and thus depletes tissue glutathione levels was used to aggravate the injury and to determine its effect on incisional healing. A 5 cm dorsal midline skin incision was performed on 40 albino Wistar rats in two groups and then closed by interrupted sutures. Groups received 0.9% NaCl and DEM at a dosage of 1 mg/kg/day intraperitoneally for seven days, respectively. On postoperative days 7 and 14, histopathological assessment and tensile strengths were measured. The DEM treated group had a marked inflammation with poorly defined collagen formation and the tensile strength measurements revealed a significant decrease (p <0.001) on the 7t day. On the other hand, the first group showed better collagenization and a lesser degree of inflammation. However, on the 14th day, there was no noticeable histopathological difference between the two groups; but, tensile strength values of the second group were still lower (p <0.05). In this animal model, DEM postponed the healing process and reduced the tensile strength.     

Effect of autocontrol micromotion intramedullary interlocking nail on fracture healing： an experimental study

Objective: To investigate the effect of autocontrol micromotion locking nail ( AMLN ) on experimental fracture healing and its mechanism. Methods: 16 goats undergoing both sides of transverse osteotomy of the femoral shafts were fixed intramedullary with AMLN and Gross-Kempf (GK) nail, respectively. The follow-up time was 7, 14, 28 and 56 days. Roentgenographic, biomechanical, histological, scanning electromicroscopic and biochemical analyses were done. Results: (1) The strength of anticompression, antiflexion and antitorsion in the fractural end in the AMLN-fixed group was higher than that of GK nail-fixed group; whereas, the rate of stress shelter in the fractured end decreased significantly (P<0.01). (2) The content of the total collagen, insoluble collagen, calcium and phosphate in the AMLN-fixed group was higher than that in the GK nail-fixed group (P<0.05). (3) Histological observation and quantitative analysis of calluses revealed that AMLN could promote the growth of bridge calluses and periosteum calluses. Hence the facture healing and remolding process achieved early, which was much better than traditional GK nail fixation. (P<0.05). (4) 7-14 days postoperation, the calluses of AMLN-fixed group was flourish and camellarly arranged and the collagen fibril formed constantly in the absorption lacuna of bone trabecula. 28-56 days postoperation, the collagen fibril was flourish around the absorption lacuna and was parallel to the bone's longitudinal axis. Active bony absorption and formation were seen, so was remolding and rebuilding. Haversian system was intact and the bony structural net was very tenacious because of the deposition of calcium salt. None of the above findings was observed in the GK nailfixed group. Conclusions: The design of AMLN accords well with the plastic fixation theory. As the geometry ametabolic system constituted by the intramedullary fixation instruments and the proximal and distal end of the fracture is very firm and stable, the disturbance to the physical stress distributed in the fractural end is light. The generation and conduct of the intermittent physical stress between the fractural parts could reach the balance between stress conduct and stress protection. The feature that the healing and remolding take place at the same time speeds up the fractural healing process.     

S-nitrosoglutathione-containing hydrogel accelerates rat cutaneous wound repair

BACKGROUND: Nitric oxide (NO) plays a key role in wound repair and S-nitrosothiols like S-nitrosoglutathione (GSNO) are well known NO donors. METHODS: Animals were separated in two groups and submitted to excisional wounds on the dorsal surface at the first day. GSNO (100 microm)-containing hydrogels were topically applied on the wound bed in the GSNO group, daily, during the first 4 days. Control group was topically treated with hydrogel without GSNO for the same period. Wound contraction and re-epithelialization were measured. Animals were sacrificed 21 days after wounding. Samples of lesion and normal tissue were formalin-fixed, paraffin embedded for histological analysis. RESULTS: Wound contraction, measured 14 and 21 days after wounding, was greater in the GSNO group than in the control group (P<0.05 for both). The re-epithelialized wound area, measured 14 days after wounding, was higher in the GSNO group than in the control group (P<0.05). A higher amount of inflammatory cells was observed in superficial and deep areas of the granulation tissue of the control group compared to the GSNO group. Twenty-one days after wounding, thin red-yellow collagen fibers arranged perpendicularly to the surface were found in the granulation tissue of the control group, whereas in the GSNO-treated group collagen fibers were thicker and arranged parallel to the surface. Increased number of mast cells was observed in the GSNO group compared with that in the control group. Vascularization and myofibroblast distribution were similar in both groups. CONCLUSION: Topical application of GSNO-containing hydrogel during the early phases of rat cutaneous wound repair accelerates wound closure and re-epithelialization and affects granulation tissue organization.