Objective To explore the effectiveness and safety of topical phenytoin for wound healing. Methods We searched MEDLINE (1966 to Oct. 2002), EMBASE (1984 to 2002), The Cochrane Library (Issue 4, 2002), Biological Abstracts (1993 to 1996), Cancerlit (1997 to Sept. 2002), Life Science Collection (1982 to Mar. 1995), International Pharmaceutical Abstracts (1970 to 2002), and CBMdisc (1978 to Jan. 2003). Controlled trials on topical phenytoin for wound healing were identified. The methodological quality of included studies was assessed, and a descriptive analysis was performed. Results Nine studies (507 cases) including 1 randomized controlled trials (RCT) and 8 non-randomized controlled trials were included. These studies were of poor methodological quality. Because there were a variety of etiology of ulcers, differnet interventions in control groups, and different outcome measures, for which meta-analysis was difficult to perform, a descriptive analysis of the results was presented. Most studies showed that topical phenytoin had better effects on improving healthy granulation appearance, increasing complete recovery rate, reducing time for complete recovery, and positive cases of bacterial culture than those of control groups. Mild side effects were observed in only one study.Conclusions The reviewers think that the inclusion studies less rigorous than randomized controlled trials could result in misleading findings.Some well designed randomized controlled trials of topical phenytoin for wound healing are warranted.
Objective To review the research progress of mesenchymal stem cells (MSCs) in burn wound repair. Methods The recent literature about MSCs involved in burn wound repair and mechanism was extensively reviewed and analyzed. Results MSCs have the capacity of self-renew, rapid proliferation, differentiation and paracrine, and promote burn wound repair through differentiating into a series of skin wound cells and regulating wound microenvironment. Conclusion MSCs have great potentials in the burn field. However, the cell survival and outcome are also facing challenges from poor microenvironment of the burn wound.
Objective To prepare nerve growth factor (NGF)-insulin composite gel and observe the effects of NGF-insulin composite gel on deep second degree scald wound healing in diabetic rats. Methods Carbomer 980, NGF (4 000 U), and insulin (800 U) were used to prepare the insulin gel, NGF gel, and NGF-insulin composite gel. The character of NGF-insulin composite gel was observed, and the in vitro drug release was tested. Seventy-five SPF Wistar male rats, weighing 200-250 g, were divided into 5 groups randomly, 15 rats each group: normal control group (group A), diabetes control group (group B), insulin gel treatment group (group C), NGF gel treatment group (group D), and NGF-insulin composite gel treatment group (group E). The type 1 diabetes rat model was established by intraperitoneal injection of Streptozotocin (55 mg/kg) in groups B, C, D, and E, while the rats in group A were injected with the same dose of citric acid and calcium citrate buffer. After modeling success, deep second degree scald wound on the back was made with constant temperature water bath box. Wounds were treated with carbomer blank gel in groups A and B, with insulin composite gel in group C, with NGF gel in group D, and with NGF-insulin composite gel in group E, once a day. At 3, 7, 11, 15, and 21 days after injury, the scald wound healing was observed and healing rate was calculated; the full-thickness skin specimens were harvested from 3 rats of each group for histological and immuohistochemical staining observation. Results The NGF-insulin composite gel was clear and transparent, and had good moisture retention capacity and adhesion; it was easy to apply and clean up. The drug release in vitro lasted more than 24 hours and maintained for 30 days. No rat died during the experiment. At 3 days after injury, wound area did not reduce in all groups; at 7, 11, 15, and 21 days, group E had the highest wound healing rate, and group B had the lowest; significant differences were found between group E and group B and when compared with the other groups (P lt; 0.05). HE staining showed that group E surpassed other groups in the growth of granulation tissue and collagen fiber. Immunohistochemical results showed that the CD34 and proliferating cell nuclear antigen (PCNA) expressed at 3 days, and the number of positive cells increased gradually with time; the microvessel density and PCNA expression were highest in group E and were lowest in group B, showing significant differences when compared with the other groups and between group E and group B (P lt; 0.05). Conclusion NGF-insulin composite gel can improve deep second degree scald wound healing in diabetic rats.
Objective To investigate the effect of the serum from severe burn patients on the biology characteristics of human umbilical cord mesenchymal stem cells (hUCMSCs) in vitro, so as to explore the feasibility of hUCMSCs transplantation for treating severe burn. Methods The 3rd passage of hUCMSCs were randomly divided into 3 groups: 10% fetal bovine serum group (group A), 10% normal serum group (group B), and 10% burn serum group (group C). At 24 hours, 72 hours, and 6 days after culture, the cell morphology and density were observed by inverted microscope; the cell proliferation was assessed by MTT; after 6 days of culture, the cell cycle by propidium iodide staining and flow cytometry, the apoptosis by acridine orange/ethidium bromide staining, and the cell senescence by β-galactosidase staining; the levels of tumor necrosis factor α (TNF-α), interleukin 1 (IL-1), platelet-derived growth factor (PDGF), and insulin-like growth factor 1 (IGF-1) in serum were detected by a double-antibody sandwich ELISA kit. Results hUCMSCs were long spindle/polygon in 3 groups. The cell fusion of group C was obviously faster than that in group A and group B. The cell proliferation curves showed that the velocity and number of cell proliferation in group C were significantly higher than those in group A and group B at 2-6 days after culture (P lt; 0.05). The rates of proliferation period (S) of hUCMSCs were 9.21% ± 1.02%, 11.79% ± 1.87%, and 20.54% ± 2.03%, respectively in groups A, B, and C at 6 days, and group C was significantly higher than that of group A and group B (P lt; 0.05). The hUCMSCs showed normal morphology and structure in 3 groups, and no apoptosis cells was observed. The positive cells percentage of group C (2.6% ± 0.1%) was significantly lower than that of group A (4.8% ± 0.2%) and group B (3.8% ± 0.4%) (P lt; 0.05). The levels of TNF-α, IL-1, PDGF, and IGF-1 in group C were significantly higher than those in group B (P lt; 0.05). Conclusion The higher levels of cytokines in serum from the severe burn patients can significantly stimulate hUCMSCs proliferation, prevent cells apoptosis, and reduce cells senescence. Therefore, it is feasible to use hUCMSCs transplantation for treating severe burn patients.
【Abstract】 Objective To evaluate the long-term effectiveness of composite grafts of acellular dermal matrix (ADM)and autologous spl it-thickness skin in repairing deep burn wounds. Methods Between June 2002 and December 2008, 30 patients (42 wound) were treated. There were 25 males and 5 females, aged 3-52 years with a median age of 31 years. Of them, 24 burned patients had 35 wounds, including 23 deep second degree and 12 third degree wounds with a mean disease duration of 24 days (range, 3-45 days); 6 patients with hyperplastic scar had 7 wounds with a mean disease duration of 16 days (range, 9-21 days). The wound locations were neck (2 wound), hand (4 wounds), forearm and elbow (8 wounds), shoulder (3 wounds), poples (6 wounds), laps (4 wounds), ankle and legs (15 wounds), and the area of wounds ranged from 10 cm × 10 cm to 30 cm × 20 cm. After thorough debridement, tangential excision, and scar excision, ADM and autologous spl it-thickness skin graft were used to repair the wounds by one-step method. Results After operation, composite skin graft survived completely in 39 wounds of 27 patients, with a survival rate of 92.9%; partial necrosis occurred in 3 wounds of 3 patients (7.1%), and healed after dressing change and secondary skin graft. The patients were followed up 30-34 months (mean, 32 months) postoperatively. The appearance of the composite grafts were smooth and soft with good elasticity and low pigmentation. The activity and function of limbs recovered well. No scar hyperplasia was observed at the donor sites. Conclusion It can achieve good outcomes in appearance and function to use ADM and autologous spl it-thickness skin graft for repairing deep burn wounds in functional regions.
Objective Endoplasmic reticulum stress (ERS) mediated apoptosis is one of the eukaryotic cellularapoptotic pathways, to investigate the potential role of ERS during myocardium apoptosis in rats with severe burninjury. Methods Sixty-four 7-week-old male Wistar rats, weighing 200-220 g, were randomly divided into 2 groups. Thirtypercentage of total body surface area full-thickness thermal injury was produced in 32 rats of burn group, while sham burn wasproduced in 32 rats of control group. The heart tissues were harvested from 8 rats in each group at 1, 4, 7, and 14 days after burnto observe the changes of myocardium ultrastructure with transmission electron microscope (TEM). Myocardium apoptosis wasdetected with TUNEL assay. The expressions of glucose regulated protein 78 (GRP 78), C/EBP-homologous protein (CHOP),and cleaved Caspase 12 in different pathways of ERS were analysed with Western blot. Results All rats survived during theexperiment. Apoptotic changes of cardiomyocytes were observed in burn group, and the apoptosis index in burn group wassignificantly higher than that in control group at each time point (P lt; 0.05), and it reached peak at 7 days after burn injury(P lt; 0.05). The expressions of myocardial GRP 78, CHOP, and cleaved Caspase 12 showed persistent elevation in burn group.The expressions of GRP 78 and cleaved Caspase 12 in burn group were significantly higher than those in control group at eachtime point (P lt; 0.05), while the expression of CHOP was higher than that in control group at the other time points (P lt; 0.05)except 1st day after burn injury. Conclusion ERS and CHOP, Caspase 12 mediated apoptotic pathway are activated inmyocardium after severe burn injury, and this may be one pathway of myocardium apoptosis.
Objective To explore the possible mechanism of nerve growth factor (NGF) mixed insul in on the angiogenesis of burn wounds and the effect on the expressions of Bcl-2 and Bax in diabetic rats. Methods A total of 75 SPF male Wistar rats, weighing 200-220 g, were selected randomly and divided into nomal control (group A, n=15), the rats with diabetic control (group B, n=15), insul in treatment (group C, n=15), NGF treatment (group D, n=15), NGF and insul in treatment (group E, n=15) groups. In groups B, C, D, and E, streptozotocin was given by intraperitoneal injection at dose of 10 mg/kg on the 1st day and 50 mg/kg on the 3rd day to prepare the diabetic rat models. In group A, citric acid buffer at the samedose was given. After 1 month of diabetic models, second degree scald was made on the back of the rats, and then wounds were treated with 3-layer normal sal ine gauze in groups A and B, with 3-layer gauze containing 5 U Novol in 30R and subcutaneous injection of Novol in 30R (4-6 U/kg) everyday in group C, with 3-layer gauze containing 5 mL NGF (25 U/mL) in group D, and with a combination of groups C and D in group E. At 7, 11, 15, and 21 days, the wound heal ing rate was calculated; at 3, 7, 11, 15, and 21 days, the expressions of Bcl-2, Bax, and CD34 were determined and the microvascular density was measured by immunohistochemistry staining. Results All rats survived till experiment was finished. The area of wounds became smaller gradually with time. Group E was better than other groups in the wound heal ing rate (P lt; 0.05), the skin keratosis, the hair growth, and the granulation tissue and collagen fibers growth. With time, the expressions of CD34 and Bcl-2 increased gradually, reached the peak at 15 days and decreased at 21 days; the expression was ber in group E than in other groups (P lt; 0.05). At 3 days, Bax did not express; at 7 days, Bax began to express in new vascular endothel ial cells and the expression increased gradually with time; the expression was weaker in group E than in other groups (P lt; 0.05). Conclusion A combination of NGF and insul in local appl ication can enhance the angiogenesis of the burn wound in diabetic rats and accelerate wound heal ing by increasing the expression of Bcl-2 and decreasing the expression of Bax and restraining apoptosis of the wounds vascular endothel ial cells of diabetic rats.
Objective To investigate the efficacy of basic fibroblast growth factor (bFGF) combined with topical oxygen therapy for deep II degree burn wounds, by comparing the effects of bFGF combined with topical oxygen therapy and bFGF with routine therapy. Methods From February 2004 to July 2009, 85 patients with deep II degree burn wounds (117 wounds) were enrolled and divided into 4 groups randomly according to different treatments. There was no significant difference in sex, age, disease course, wound size, and wound treatment size among 4 groups (P gt; 0.05). In group A, 18 patients (28 wounds) were treated routinely; in group B, 23 patients (30 wounds) were treated with routine methods and topical oxygen therapy; in group C, 19 patients (25 wounds) were treated with routine methods and bFGF therapy; and in group D, 25 patients (34 wounds) were treated with routine methods and bFGF/topical oxygen therapy. Topical oxygen therapy was administered to the wound for 90 minutes per day for 3 weeks. The bFGF therapy was appl ied everyday (150 U/ cm2) for 3 weeks. Results All cases were followed up 6-12 months (9 months on average). The wound heal ing times in groups A, B, C, and D were (27.3 ± 6.6), (24.2 ± 5.8), (22.2 ± 6.8), and (18.2 ± 4.8) days, respectively; showing significant difference between group A and group D (P lt; 0.05). The wound heal ing rates in groups A, B, C, and Dwere 67.8% ± 12.1%, 85.1% ± 7.5%, 89.2% ± 8.3%, and 96.1% ± 5.6%, respectively; showing significant differences between group A and groups B, C, D (P lt; 0.05). The therapic effective rates in groups A, B, C, and D were 75%, 90%, 92%, and 100%, respectively; showing significant difference between group A and group D (P lt; 0.05). The Vancouver scar scale scoring of group D 6 months after treatment was better than that of group A (P lt; 0.05). Conclusion The bFGF combined with topical oxygen therapy can enhance deep II degree burn wound heal ing. Furthermore, the therapy method is simple and convenient.
Objective To explore the appl ication of damage control surgery (DCS) strategy in the treatment of severe burn-trauma combined injury. Methods From January 2004 to December 2009, 28 patients with severe burn-trauma combined injury received salvage treatment according to DCS, including 12 cases of burn combining injury at 2 sites, 6 cases ofburn combining injury at 3 sites, and 10 cases of burn combining injury at 4 sites or above. There were 18 males and 10 females with a median age of 39.5 years (range, 8-56 years). The burn area was 15% to 56% of total body surface area. The injury severity score a (ISS) was 25 to 56, and the traumatic index was 17 to 24. Lethal triad syndrome occurred in all patients. Of them, 16 cases were on admission immediatly after first-aid, and 12 cases were thansferred from other hospitals. The time from injury to hospital ization was 20 minutes to 36 hours. All patients were treated by immediate fluid resuscitation and emergent operation to control hemorrhage and contaminations. Biological dressings were used to seal the wounds provisionally. The systemic therapy was carried out as soon as the vital signs of the patients became stable. Results In 26 survivors, 23 achieved wound heal ing by first intention, 3 had a l ittle residual wound at discharge. The hospital ization days were 31 to 398 days (62 days on average). However, 1 patient died of multiple organ failure, another 1 patient died of severe cerebral trauma with refractory shock. Conclusion The DCS strategy is effective in reducing mortal ity of patients with severe burn-trauma combined injury.
Objective To investigate the effect of topical appl ication of insul in on the burn wound heal ing in aging diabetes mell itus (DM) rats and to explore its mechanism. Methods Seventy-five SPF Wistar rats (female and/or male), aged 12-24 months and weighing 300-350 g, were selected and randomly divided into group A (burn control group, n=25), group B(DM burn control group, n=25), and group C (DM insul in treatment group, n=25). The rats in group B and group C were fedwith high-fat, high-protein, and high-sugar forage for 1 month and received intraperitoneal injection of streptozotocin (STZ)to establ ish experimental model of aging DM. The rats were fed with high-fat, high-protein, and high-sugar forage for another 8 weeks. Then, the deep second-degree burn model was establ ished in the rats of group B and group C. The wounds in group A and B underwent local subcutaneous injection of 2 mL isotonic sal ine and group C received local subcutaneous injection of 0.1 U insul in. The rate of wound heal ing was calculated 7, 14, and 21 days after burn injury. At 1, 3, 7, 14, and 21 days after burn injury, HE staining observation, immunohistochemistry staining for CD34, detection of sugar and hydroxyprol ine (HOP) content in wound tissue, and microvessel density (MVD) calculation were performed. Results At 7, 14, and 21 days after burn injury, the wound heal ing rates of group A and group C was significantly higher than that of group B (P lt; 0.05), and there was no significant difference between group A and group C (P gt; 0.05). Histology observation at 21 days after burn injury: in group A, certain degree of epithel ization was evident in the wound epithel ium; in group B, large quantity of necrotic tissue was evident; in group C, complete epithl ization occurred in the wound epithel ium with better epithel ial cell differentiation and more neonatal collagen. For the sugar content in the wound tissue, group A was significantly lower than group B or group C at 1, 3, 7, 14, and 21 days (P lt; 0.05) and group C was significantly lower than group B at 7, 14, and 21 days (P lt; 0.05). For the HOP content in the wound tissue and the MVD count, group A or group C was significantly higher than group B (P lt; 0.05) and there was no significant difference between group A and group C (P gt; 0.05). CD34 expression: in group A, it was (+) at 7 days, (++) at 14 days, and (+++) at 21 days; in group B, it was (+) at 14 and 21 days; in group C, it was (++) at 7 days and (+++) at 14 and 21 days. Conclusion Topical appl ication of insul in can promote the synthesis of wound collagen, accelerate the woundangiogenesis, and speed up the wound heal ing in aging DM rats.