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Abstract: Mammalian target of rapamycin (mTOR) is an important mediator for cross talk between nutritional signals and metabolic signals of insulin by downregulating insulin receptor substrate proteins. Therefore, mTOR inhibition could become a therapeutic strategy in insulin-resistant states, including insulin resistance induced by burn. We tested this hypothesis in the rat model of 30% TBSA full thickness burn, using the mTOR inhibitor rapamycin. Rapamycin (0.4mg/kg, i.p.) was injected 2h before euglycemic–hyperinsulinemic glucose clamps at 4 days after burn. IRS-1, phospho-serine307, phospho-tyrosine of IRS-1 and phospho-mTOR in muscle tissue were determined by immunoprecipitation and Western blot analysis or immunohistochemistry. Plasma TNF-α, insulin and C-peptide were determined before and after euglycemic–hyperinsulinemic glucose clamps. Our data showed that TNF-α, insulin and C-peptide significantly increased in the early stage after burn (P <0.01). The infused rates of total 10% glucose (GIR, mg/kgmin) significantly decreased at 4 days after burn. The level of IRS-1 serine307 phosphorylation in muscle in vivo significantly increased after burn (P <0.01), while insulin-induced tyrosine phosphorylation of IRS-1 significantly decreased (P <0.01). Inhibition of mTOR by rapamycin inhibited the phosphorylation of mTOR, reduced serine307 phosphorylation, elevated tyrosine phosphorylation and partly prevented the decrease of GIR after burn. However, TNF-α, insulin and C-peptide were not decreased by rapamycin treatment postburn. Taken together, these results indicate that the mTOR pathway is an important modulator of the signals involved in the acute regulation of insulin-stimulated glucose metabolism, and at least, partly contributes to burn-induced insulin resistance. mTOR inhibition may become a therapeutic strategy in insulin-resistant states after burn. [Copyright &y& Elsevier]

Burn wound excision and grafting is a common clinical practice that decreases patient morbidity and mortality. It is not known, however, if the salutary effects of this procedure are related to effects on interleukin 6 (IL-6) and tumor necrosis factor (TNF-) α, and to reducing insulin resistance after burn. Sprague–Dawley rats were randomly divided into three groups: control, burn, burn±excision groups. Rats in burn group were given a third-degree scald burn covering 30% total body surface area (TBSA) and no wound excision. Rats in burn±excision group were subjected to a 30% third-degree burn followed by complete excision and allografting of the injury site within 15min after burn. The rats in control group were treated in the same manner as the burn group, except that they were immersed in a room-temperature water. Glucose tolerance tests (GTT) were observed at 3 days after burn, euglycemic–hyperinsulinemic glucose clamps were performed at 4 days after burn and interleukin 6 (IL-6) and tumor necrosis factor (TNF-) α were determined after euglycemic–hyperinsulinemic glucose clamps. The levels of IL-6 and TNF-α increased after burn. Significant differences in GTT were observed between control and burn groups, and the rate of glucose infused measured in burned rats was significantly decreased compared with that in control at 4 days after burn. Early excision and grafting significantly decreased levels of IL-6 and TNF-α, and further reduced insulin resistance following thermal injury compared with burn group. Conclusion: Early excision and grafting appeared to have an effect on inflammatory mediators and further reduced insulin resistance induced by major burns. [Copyright &y& Elsevier]

Abstract: The aim of this study was to investigate the changes of glucose tolerance, insulin sensitivity, and euglycemic–hyperinsulinemic glucose clamps following a 30% TBSA full thickness third degree burn in rats. Sprague–Dawley rats weighing 160–170g received 30% TBSA full thickness third degree burn by immersing the back of trunk for 12s in a boiling water bath under anesthesia. Weight- and time-matched sham burn group (control) was treated in the same manner as the trauma group, except that they were immersed in a room-temperature water bath. After 12h overnight fasting, plasma insulin concentration was determined by ELISA using rat-insulin enzyme immunoassay kit (SPI-BIO) and blood glucose was assayed by glucose analyzer at 3 days after burn. Insulin sensitivity index was calculated by using slightly modified formula. The rat was injected with 5% glucose (2g/kg body weight, intraperitoneally) to observe the change of glucose tolerance at 3 days after burn. Euglycemic–hyperinsulinemic glucose clamps were performed at 4 days after burn. Insulin sensitivity index of burn group was significantly reduced compared with control group at 3 days after burn (0.58±0.23 versus 1.23±0.16, P <0.01). The significant difference of glucose tolerance was observed between the two groups and the glucose infused rate measured in burned rats was significantly decreased compared with that in control at 4 days after injury (7.23±1.35 versus 12.31±0.54, P <0.01). Conclusion: Burn causes the significant change of glucose metabolism and results in insulin resistance in rats. [Copyright &y& Elsevier]

SUMMARY: OBJECTIVE The purpose of this study was to determine the expression and regulation of vascular cell adhesion molecule (VCAM)-1 in human umbilical vein endothelial cells (HUVECs) induced by sera from severely burned patients.DESIGN Controlled laboratory study.SETTINGS Research laboratory in a university hospital.SUBJECTS HUVECs.INTERVENTIONS HUVECs were incubated with serum from eight healthy controls and eight patients with thermal injuries of >50% total body surface area. The experiment was repeated after pretreatment with pyrrolidine dithiocarbamate, an inhibitory effect on nuclear factor-κB activation, SB203580, a specific p38 mitogen-activated protein kinase inhibitor, and PD98059, a mitogen-activated protein/extracellular signal-regulated kinase inhibitor.MEASUREMENTS AND MAIN RESULTS Protein and messenger RNA expression of VCAM-1 was measured by flow cytometry and reverse transcription-polymerase chain reaction respectively. Soluble VCAM-1 level in HUVECs culture supernatants was measured by enzyme-linked immunosorbent assay. Sera from severely burned patients showed a stimulatory effect on VCAM-1 messenger RNA levels and an increased VCAM-1 expression on the endothelial cell surfaces. The soluble form of VCAM-1 molecules was also elevated by the stimulation of burn sera. In vitro peripheral blood mononuclear leukocytes adherence to HUVECs incubated with burn sera was significantly increased compared with those incubated with control sera. Finally, these events were significantly inhibited by pretreatment with antioxidants pyrrolidine dithiocarbamate or SB203580, whereas PD98059 had no significant effect.CONCLUSIONS These findings suggest that sera from severely burned patients induced up-regulation of VCAM-1 expressions in HUVECs, and this process might be largely dependent on oxidant-mediated nuclear factor-κB activation and p38 mitogen-activated protein kinase pathways. [ABSTRACT FROM AUTHOR]

Studies the changes in cardiac contractile function and myocardial intercellular calcium levels after burn trauma. Mechanical performance of perfused hearts; Myocardial energy metabolism; Calculated left ventricular developed pressure.

Wound healing is a dynamic and complex biologic process that could be accelerated by growth factors. To investigate the efficacy of topical recombinant human acidic fibroblast growth factor (rh-aFGF) treatment in deep partial-thickness burn or skin graft donor sites, we designed a randomized, multicenter, double-blind, and placebo-controlled clinical trial. The healing rate, fully healed rate, and healing time were evaluated to assess the efficacy of rh-aFGF application. Laboratory examinations and abnormal signs were used to assess the side and toxic effects. The results showed that the healing rate of burn wounds and skin graft donor sites treated by rh-aFGF was significantly higher than that by placebo, and the mean healed time of burn wounds and skin graft donor sites in the rh-aFGF group was significantly the shorter than that in the placebo group. In conclusion, topical administration of rh-aFGF can accelerate the wound healing process and shorten the healed time. It is a potential therapeutic application for promoting healing of deep partial-thickness burns or skin graft donor sites. [ABSTRACT FROM AUTHOR]

This study aimed to elucidate the effect of depression on the healing of acute wounds in rats. We hypothesized that depression would have negative effects on inflammation and wound healing and that antidepressant therapy would reverse these effects. This study included 100 rats randomly allocated into five groups: control group (CG), depression group (DG), pre‐depression group (PDG), antidepressant group (AG), and pre‐antidepressant group (PAG). Acute wounds were created on the rats' backs. The groups were subjected to no interventions (CG), aversive stimuli before (PDG) and after (DG) wound creation, and antidepressant treatment before (PAG) and after (AG) wound creation. On the day of wound creation and on days 3, 6, 9, and 12 after wound creation, observations of the wound area and degree of depression (evaluated using the sucrose preference test, open‐field test, and weight change) were recorded. On days 6 and 12 after wound creation, venous serum and wound tissues were collected. Tumor necrosis factor alpha (TNF‐α), interleukin (IL)‐1β, IL‐6, and IL‐10 levels were measured using the enzyme‐linked immunosorbent assay. Results showed an initial increase followed by a decrease in the degree of depression in all groups except DG (continuous decline). The wound‐healing rate was significantly lower in PDG and DG than in CG; it was higher in AG and PAG than in CG. DG and PDG had higher concentrations of inflammatory cytokines than CG, and AG and PAG had lower concentrations than CG. This indicates that the onset of depression delays the healing of acute wounds and aggravates the inflammatory response in rats. Antidepressant treatment counteracts both of these negative effects. [ABSTRACT FROM AUTHOR]

Background Microskin autografts with conventional wrap and compression are used extensively in the treatment of skin and tissue defects. This comparative study aimed at investigation of the clinical application of negative pressure wound therapy (NPWT) in combination with microskin autografts for repair of acute and chronic wounds. Methods A prospective case-control study was performed from December 1, 2010-December 31, 2013 in Changhai Hospital, Shanghai. We compared a study group of patients received microskin autografting covered by NPWT with that of a control group of patients received microskin autografting covered by a conventional gauze. Results A total of 81 patients were in this study, 27 patients were allocated to the study group and 54 patients to the control group. The study group exhibited significant low infection rate and pain score during removal of inner layer at first dressing change after skin grafting compared with those of the control group (P < 0.05). The time interval between skin grafting and first postoperative change was longer in the study group than that in the control group (P < 0.01), the study group showed a significant shorter 95% wound healing time (P < 0.05), and survival rate of microskin autografts in the study group was higher than that in the control group (P < 0.05). Conclusions NPWT is beneficial for wound closure after microskin autografts, which prolongs the interval between skin transplantation and first postoperative dressing change, reduces pain during removal of inner layer dressing, increases skin graft survival rate, and shortens wound healing time. Therefore, NPWT can be recommended for repair of acute and chronic wounds with microskin autografts. [ABSTRACT FROM AUTHOR]

Interleukin- (IL-) 37 is a novel anti-inflammatory cytokine that suppresses immune response and inflammation. This study was performed to determine whether IL-37 was elevated in patients with rheumatoid arthritis (RA) and investigate the correlation between IL-37 level and disease activity and the concentration of Th1/Th2/Th17-related cytokines. Clinical parameters of disease activity, including the 28-joint disease activity score (DAS28) and C-reactive protein (CRP), were collected in 34 RA patients and 34 age- and sex-matched healthy controls. Plasma IL-37 was measured by ELISA. Plasma levels of TNF-α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, IL-17, G-CSF, GM-CSF, IFN-γ, MCP-1, and MIP-1β were analyzed using the Bio-Plex suspension array system. It was found that IL-37 levels were elevated markedly in RA patients and almost undetectable in healthy controls. In addition, IL-37 levels in patients with active RA were significantly enhanced as compared with those in patients of remission. More importantly, IL-37 showed a significant correlation with disease activity (DAS28) and IL-4, IL-7, IL-10, IL-12, and IL-13 concentrations in RA patients. These findings suggest that IL-37 plays an important role in the pathogenesis of RA and may prove to be a potential biomarker of active RA. [ABSTRACT FROM AUTHOR]

Background Accurate estimation of a burned area is crucial to decisions about fluid resuscitation, surgical options, nutritional support, and prognosis. Widely used clinical methods to estimate a burn area are two-dimensional. They do not consider age, sex, body mass, physical deformities, or other relevant factors. Computer-aided methods have improved the accuracy of estimating burned areas by including data analysis and reducing subjective differences. Threedimensional (3D) scanning allows us to determine body dimensions rapidly and reproducibly. We describe an individualized, cost-efficient, portable 3D scanning system, BurnCalc, that can create an individual 3D model and then calculate body surface area (BSA) and the burn area accurately and quickly. Methods The BurnCalc system was validated by verifying the accuracy and stability of BSA calculation. We measured 10 regular objects in experiment 1, using Student's t-test and the intraclass correlation coefficient (ICC) in the analysis. In experiment 2, artificial paper patches of known dimensions were attached to various parts of the body of 40 volunteers. Their sizes were then calculated using BurnCalc. The BurnCalc data were compared to actually measured values to verify accuracy and stability. Total BSAs of these 40 volunteers were also calculated by BurnCalc and compared to those derived from an accepted formula. In experiment 3, four experts using Chinese Rule-of-Nines or Rule-of-Palms methods calculated the percentages of the total BSA in 17 volunteers. Student's t-test and ICC, respectively, were used to compare the results obtained with the BurnCalc technique. Results Statistically, in experiment 1, p = 0.834 and ICC = 0.999, demonstrating that there was no difference between the BurnCalc and real measurements. Also, the hypothesis of null difference among measures (experiment 2) was true because p > 0.05 and ICC = 0.999, indicating that calculations of the total BSA and the burn area were more accurate using the BurnCalc technology. The reliability of the BurnCalc program was 99.9%. In experiment 3, only the BurnCalc method exhibited values of p > 0.05 (p = 0.774) and ICC = 0.999. Conclusions BurnCalc technology produced stable, accurate readings, suggesting that BurnCalc could be regarded as a new standard clinical method. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: This study was designed to develop and test a Chinese burn patient-specific quality of life (QOL) scale based on the burn-specific health scale – brief (BSHS – B) to provide an effective assessment tool to measure quality of life in Chinese burn patients. Method: Delphi method was used after the translation, back translation and pre-commissioning tests of BSHS – B, to amend the description of the items for cultural adaptation. The adapted Chinese version (ACV) of the BSHS – B was tested for internal consistency and validity of construct on a group of 271 burn patients from three major burn units in China. Results: Thirty-eight items within six domains of ACV BSHS-B were developed with scoring ‘0–4’ in each item. The mean total score for our study group was 98.36 (standard deviation (S.D.)=37.86), ranging from 13 to 150. The total Cronbach''s alpha value was 0.97 and total split-half reliability was 0.98, demonstrating that the internal consistency of the ACV was very high. Pearson correlations among the six domains of ACV BSHS – B were statistically significant. Exploratory factor analysis results showed that the six-factor function explained 78.30% of total variance; each entry in the corresponding domain had a factor-loading value higher than 0.4, indicating that the scale has a good validity. Conclusion: The ACV of the BSHS – B showed good reliability and validity, and can be used as a tool for assessing the QOL in Chinese burn patients. [Copyright &y& Elsevier]

The purpose of present study was to explore the possibility of Tec kinase as a mediator for IL-8 transcription in monocytes stimulated with LPS. Plasmids of mouse Tec kinase IV or Tec kinase IV with inactivating point mutations generated with QuikChange site-directed mutagenesis were co-transfected with IL-8 promoter driven luciferase construct into RAW264.7 cells, then luciferase activity was measured with a luminometer. The results shown Tec kinase could significantly enhance IL-8 transcription. Furthermore, point inactivating mutation in SH2, PH or PTK domain almost completely abolish the effects of Tec kinase on the transcription of IL-8. In the transfection experiment, PD98059, a MEK1 inhibitor, decreased the transcription of IL-8 in a dose dependent pattern. When siRNA for Tec kinase was transfected into THP-1 cells, it could efficiently block the production of IL-8 from THP-1 cells ( p < 0.01) stimulated with LPS. In conclusion, Tec kinase may mediate the transcription of IL-8 in monocyte stimulated with LPS. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To reveal the characteristic and distribution of length of hospital stay (LOS) and direct hospitalisation costs of paediatric scald. Methods: A prospective case series observation was performed from January 2005 to December 2006 at the Burn Center, Changhai Hospital, Shanghai, China. The information, such as demographics, clinical diagnosis and treatments since admission, of the paediatric scald patients included in the series was recorded. The direct cost of a treatment event was recorded into the price system when it was incurred. All cost data were summarised on completion of the study. The distribution of LOS and the hospitalisation costs were recorded by gender, age, total burn area, depth of burn, blood transfusion and patterns of treatment. Mann–Whitney signed-rank test was used to assess the differences between continuous, non-normally distributed variables, and multiple linear regression was used to model LOS and direct hospitalisation costs. Statistical analyses were undertaken with SPSS 15.0 statistical software. Results: Patients aged 3 years or less accounted for more than half of the total LOS and hospitalisation costs, patients with burn area less than 10%TBSA (total burn surface area) accounted for more than 70% of the total LOS and more than half of the hospitalisation costs and patients with second-degree burn accounted for more than 78% of the total LOS and hospitalisation costs. Depth of burn, area of burn, patterns of treatment and blood transfusion were independent predictors of LOS; whereas LOS, area of burn and blood transfusion were independent predictors of hospitalisation costs. Conclusion: Paediatric scalds have particular characteristics in terms of distribution of LOS and direct hospitalisation costs and the factors influencing them. The data presented in this study should assist burn care practitioners and hospital epidemiologists estimate and compare the economic burden of paediatric burns at other institutions; it may also be useful in resource allocation and cost-effectiveness analysis of treatment versus prevention strategies. [Copyright &y& Elsevier]