Guang-Qing Wang

Role of p38 mitogen-activated protein kinase in lung injury after burn trauma.

This study was undertaken to evaluate the effect of SB203580, a specific p38 mitogen-activated protein (MAP) kinase inhibitor, on burn-induced lung injury as well as the release of tumor necrosis factor (TNF)-&agr; and interleukin (IL)-1&bgr; in rats to characterize the role of p38 MAP kinase in lung injury after burn trauma. Sprague-Dawley rats were divided into three groups: 1) sham group, or rats who underwent sham burn; 2) control group, or rats given third-degree burns over 30% total body surface area (TBSA) and lactated Ringer solution for resuscitation; and 3) SB203580 group, or rats given burn injury and lactated Ringers solution with SB203580 inside for resuscitation. Pulmonary injury was assessed at 24 h by pulmonary capillary permeability determined with fluorescein isothiocyanate-labeled albumin and lung histologic analysis. TNF-&agr; and IL-1&bgr; protein in bronchoalveolar lavage fluid and serum were measured by enzyme-linked immunosorbent assay and p38 MAP kinase was activity determined in lung by Western blot analysis. These studies showed that significant activation of p38 MAP kinase at 24 h postburn compared with control. Burn trauma resulted in increased pulmonary capillary leakage permeability, elevated levels of TNF-&agr; and IL-1&bgr; in bronchoalveolar lavage fluid and serum, and worsened histologic condition. SB203580 inhibited the activation of p38 MAP kinase, reduced the levels of TNF-&agr; and IL-1&bgr;, and prevented burn-mediated lung injury. These data suggest that p38 MAP kinase activation is one important aspect of the signaling event that may mediate the release of TNF-&agr; and IL-1&bgr; and contributes to burn-induced lung injury.

Role of p38 mitogen-activated protein kinase in Kupffer cell secretion of the proinflammatory cytokines after burn trauma.

This study was designed to investigate the role of p38 mitogen-activated protein (MAP) kinase on Kupffer cells (KCs) secretion of proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta and hepatic injury following burn trauma. Sprague-Dawley rats were randomized into four groups: (1) sham burn rats given vehicle, (2) sham burn rats given the p38 MAP kinase inhibitor SB203580 (10mg/kg i.v., 15min and 12h after sham burn), (3) rats given a 30% total body surface area (TBSA) full-thickness burn and fluid resuscitation plus vehicle, and (4) burn rats given injury and fluid resuscitation plus SB203580. Rats from each group were killed at 24h post-burn to examine plasma aspartate transaminase (AST) and alanine transaminase (ALT) and KCs were isolated. The KCs secretion of TNF-alpha and IL-1beta and p38 MAP kinase activity (by Western blot analysis) were also examined. These studies showed by more significant activation of p38 MAP kinase in KCs harvested from burn rats than from shams. Burn trauma resulted in hepatic dysfunction and promoted KCs secretion of TNF-alpha and IL-1beta. SB203580 inhibited p38 MAP kinase activity, reduced KCs secretion of proinflammatory cytokines, and alleviated burn-mediated hepatic dysfunction. These data suggest p38 MAP kinase activation is one important aspect of the signaling event that may mediate the KCs secretion of proinflammatory cytokines TNF-alpha and IL-1beta following burn trauma.

Cardiac apoptosis in burned rats with delayed fluid resuscitation

Clinical and experimental studies have shown that delayed fluid resuscitation postburn decreases heart function. We hypothesized that apoptosis occurs in the cardiomyocyte in this condition. To investigate this hypothesis, rats were burned, fluid resuscitation was delayed, and the integrity of cardiac genomic DNA in the burned rats was determined with an LM-PCR Ladder Assay kit. DNA fragmentation shown as DNA ladders on gels, the hallmark of apoptosis, was found in the heart tissue of these rats. In the early phase of delayed fluid resuscitation, the nuclear factor kappa B (NF-kappa B) was examined using an electrophoretic mobility shift assay and was found to be activated. In comparison with burned rats with immediate fluid resuscitation, nitric oxide levels in hearts from burned rats with delayed fluid resuscitation were significantly lower (P<0.01). These results suggest that apoptosis may be an important pathway for cardiac injury, which may result from the activation of NF-kappa B and decreased nitric oxide levels.

Pathogenic alteration in severe burn wounds

The present study aims to define the trend of time related changes with local bacterial alteration of bacterial resistance in severe burns in our burn center during a 12-year period. Retrospective analysis of microbiological results on severely burned wounds between 1998 and 2009 was carried out. A study of 3615 microbial isolates was performed. Staphylococcus aureus was the most commonly isolated pathogen (38.2%) followed by A. baumannii (16.2%), Streptococcus viridans (11.4%), Pseudomonas aeruginosa (10.4%), coagulase-negative staphylococci (CNS, 9.2%). The species ratios of S. aureus and A. baumannii increased significantly from 1st to 8th week of hospitalization, while those of Streptococcus viridans, P. aeruginosa and coagulase-negative staphylococci decreased during the same period. Bacterial resistance rates were compared between the periods 1998-2003 and 2004-2009. Vancomycin remained as the most sensitive antibiotic in S. aureus including methicillin-resistant S. aureus (MRSA). It was very likely that the majority of infections caused by Streptococcus viridans, P. aeruginosa and coagulase-negative staphylococci occurred in the early stage of burn course and the majority of infections caused by A. baumannii occurred 4 weeks after admission. The use of different antibiotics was probably the major contributor to these trends.

Expression and regulation of vascular cell adhesion molecule-1 in human umbilical vein endothelial cells induced by sera from severely burned patients.

ObjectiveThe 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. DesignControlled laboratory study. SettingsResearch laboratory in a university hospital. SubjectsHUVECs. InterventionsHUVECs 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-&kgr;B activation, SB203580, a specific p38 mitogen-activated protein kinase inhibitor, and PD98059, a mitogen-activated protein/extracellular signal-regulated kinase inhibitor. Measurements and Main ResultsProtein 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. ConclusionsThese 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-&kgr;B activation and p38 mitogen-activated protein kinase pathways.

Reduction of CD47 on monocytes correlates with MODS in burn patients

Alternation of surface markers on monocytes is associated with the development of inflammation. The goals of the present study were to detect CD47 expression on monocytes by flow cytometry and explore its relationship with disease severity and MODS in burned patients. The results show CD47 expression on monocytes from all burned patients (n = 21) was lower than that from the healthy population (n = 21) for 24 days after burn. There was a significant difference in CD47 expression on monocytes between the patients with differing burn severity in the first 7 days after injury (P < 0.05). Considering the relationship between CD47 expression and MODS, we found the CD47 expression on monocytes from patients with MODS was lower (P < 0.05) in the first 3 days after injury than that from patients without MODS. In conclusion, diminished CD47 expression on monocytes is associated with burn severity and the occurrence of MODS in burn patients.

Transplantation of epidermis of scar tissue on acellular dermal matrix.

This study enrolled 22 participants with hypertrophic scarring after burn who received treatment with co-transplantation of acellular dermal matrix and epidermis of either normal skin or scar tissue. Scar thickness was evaluated with high frequency ultrasonography and the distribution of keratinocyte stem cells was detected by immunostaining. The results showed p63-positive keratinocyte stem cells throughout the epidermis of scar tissue. However, if co-transplanted on acellular dermal matrix, this effectively inhibited scar formation and pruritus, providing an alternative method to treat hypertrophic scarring.

Successful treatment of a patient with an extraordinarily large deep burn.

Summary Background Treatment of extraordinarily large deep burns remains a huge clinical challenge. Case Report This article is a summary of our experience with the treatment of a patient with an extraordinarily large deep burn (99.5% TBSA and 23% fourth degree burn) by using the “microskin autografting and alloskin repeated grafting” method to close the deep burn wound because of scarcity of skin sources of the patient. Conclusions The patient has been observed for 2 years, and is able to face the reality of life peacefully with the support of his family.

Risk factors and prognosis of lower digestive tract haemorrhage in severe burns: a 12-year retrospective analysis.

OBJECTIVE To explore the risk factors relating to lower digestive tract haemorrhage in severe burns and summarise the experience in clinical diagnosis and treatment. METHOD General data of 103 patients with severe extensive burns (EBs) admitted to our burn centre in Shanghai between 1997 and 2009 were reviewed retrospectively. The risk factors relating to EB-complicated lower digestive tract haemorrhage were analysed systematically with respect to the clinical features and experiences in treatment, and prognosis. RESULTS Of the 103 severe EBs, five developed lower digestive tract haemorrhage with an occurrence of 4.9%. Four of them were proved to have multiple mucosal erosions in caecum, colon and rectum, and the remaining one was proved rectal ulcerative haemorrhage. In comparison with upper digestive tract haemorrhage, lower digestive tract haemorrhage in the present group was characterised by a longer duration (median 4.0 days, interquartile range (IQR) 1.5-14.5 days vs. median 2.0 days (IQR 1.0-3.0 days), P < 0.05). Deep burns, especially fourth-degree burns, with complications of severe systemic infection, formed the main risk factors relating to lower digestive tract haemorrhage in severe EB patients. CONCLUSION Severe EB-complicated lower digestive tract haemorrhage is a critical condition in burns, which usually have deep wounds with severe infection surfaces that are difficult to deal with. Enteroscopic haemostasis in controlling lower digestive tract haemorrhage is usually ineffective. Clinical experiences indicate that early management of the wound with effective preventive and therapeutive measures for infection control may be a good choice in the prevention and treatment of lower digestive tract haemorrhage leading to improvement in its prognosis.