Using negative pressure wound therapy on microskin autograft wounds.

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.

Deficiency of Smad3 results in enhanced inducible nitric oxide synthase-mediated hypotension in lipopolysaccharide-induced endotoxemia.

BACKGROUND: Smad3 is a principal intracellular mediator of signaling for transforming growth factor ß, a cytokine involved in pleiotropic pathophysiological processes including inflammation and immunity. The function of Smad3 in regulating inducible nitric oxide synthase (iNOS) expression and septic shock has not been characterized. METHODS: Smad3(-/-) (referred hereafter as KO) and wild-type (WT) mice were injected intraperitoneally with lipopolysaccharide (LPS) to induce the septic hypotension. Mortality, blood pressure, and plasma levels of nitrite were measured. The iNOS messenger RNA and protein levels in lung, kidney, and spleen were also analyzed. RESULTS: Mice lacking functional Smad3 respond to LPS with greater mortality than their WT littermates. The high mortality of KO mice is accompanied by enhanced hypotension after intraperitoneal injection of LPS. Both KO and WT mice displayed an increase in plasma nitrite during the experimental period; however, LPS administration caused more dramatic changes in KO mice than WT mice. Likewise, the iNOS messenger RNA and protein levels in lung, kidney, and spleen were more strongly increased in KO mice than in WT mice after LPS administration. CONCLUSIONS: Defects in the Smad3 gene may increase susceptibility to the development of septic hypotension because of enhanced iNOS production.

Role of inhibition of p38 mitogen-activated protein kinase in liver dysfunction after hemorrhagic shock and resuscitation.

BACKGROUND: The liver is one of the organs most frequently affected by trauma and hemorrhagic shock; the exact role of p38 mitogen-activated protein kinase (MAPK) activation in response to hepatic hemorrhagic shock/resuscitation (HS/R) remains unclear. MATERIALS AND METHODS: C57Bl/6 mice were divided into four groups: sham-operated group, SB-only group, control group, and SB + HS/R group. Hepatocellular injury (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) and tumor necrosis factor (TNF-α) and interleukin (IL-1ß) messenger ribonucleic acid (mRNA) expression in the liver were assessed 6 h after resuscitation, p38 MAPK activation in the liver was assessed at 30 min after resuscitation. RESULTS: p38 MAPK activation was higher in the control group than other groups 30 min after resuscitation. p38 MAPK activation level in the SB + HS/R group did not change significantly compared with that of sham and SB-only groups, but was significantly lower than that in the control group. The TNF-α mRNA expression in the control group was significantly higher than that in the sham group. The TNF-α mRNA levels after HS/R in the SB + HS/R group were significantly lower than those in the control group and were roughly the same as those in the sham and SB-only groups. IL-1ß mRNA expression showed similar changes in the four groups. Serum ALT and AST levels in the control group were significantly higher than those in the sham group. The increase in serum ALT and AST levels after HS/R in the SB + HS/R group was significantly less pronounced than that in the control group and markedly higher than that in the sham group. CONCLUSIONS: p38 MAPK was phosphorylated during the HS/R process. Inhibiting the activation of p38 MAPK may attenuate HS/R injury to the liver.

Epidemiology and outcome analysis of severe extensive burns: a 12-year summary of 103 cases in a burn center in China.

The purpose of this article is to improve the treatment of severe extensive burns (SEB) patients by summarizing treatment experience in recent 12 years in China and analyzing the follow-up quality of life (QOL) in these patients. Clinical data and rescue measures of 103 SEB patients (≥70% TBSA) admitted in a burn center in Shanghai between 1997 and 2009 were reviewed, and QOL and hand function of those who survived more than 2 years were assessed by Brief Version of Burn Specific Health scale-B and Michigan Hand Outcome Questionnaire. Of these, 76.7% were caused by flames and 15.5% caused by scald. The median burn area was 87.5% (interquartile range, 77.0-95.0%) TBSA, of which third-degree burns accounted for 56.5% (interquartile range, 25.8-80.0%) TBSA; 71.8% were complicated by inhalation injury. The occurrence of in-hospital complications was 75.7%, with the respiratory system complications predominating (49.5%). The fatality rate was 28.2%, mainly due to sepsis and multiple organ dysfunction syndrome. Work, body image, and heat sensitivity got the lowest Brief Version of Burn Specific Health scale-B scores in all nine domains, and Michigan Hand Outcome Questionnaire scores were also relatively poor. Flame burns remain to be the main cause of SEB in China in recent 12 years. Treatment is still challenged because of the depth and extensive burn area and high occurrence of multiple system complications. How to ameliorate QOL of SEB patients, intensify the functional rehabilitation, and improve their physical appearance in particular remain to be a crux.

TLR4 mediates lung injury and inflammation in intestinal ischemia-reperfusion.

BACKGROUND: Splanchnic ischemia is common in critically ill patients, and it can result in injury not only of the intestine but also in distant organs, particularly in the lung. Local inflammatory changes play a pivotal role in the development of acute lung injury after intestinal ischemia, but the underlying molecular mechanisms are not fully understood. We sought to examine the role of Toll-like receptor 4 (TLR4) in the mouse model of intestinal ischemia-reperfusion (I/R)-induced lung injury and inflammation. MATERIALS AND METHODS: Adult male TLR4 mutant (C3H/HeJ) mice and TLR4 wild-type (WT) (C3H/HeOuJ) mice were subjected to 40 min of intestinal ischemia by clamping the superior mesenteric artery followed by 6 h of reperfusion. Lung histology was assessed and parameters of pulmonary microvascular permeability, inflammatory cytokine expression, and neutrophil infiltration were measured. Activation of mitogen-activated protein kinases (MAPKs) and the transcription factors nuclear factor κB (NF-κB) and activator protein-1 (AP-1) in the lungs were also detected. RESULTS: After intestinal I/R, lungs from TLR4 mutant mice demonstrated a significantly lower histological injury, a marked reduction of epithelial apoptosis associated with the decreased level of cleaved caspase-3 and the increased ratio of Bcl-xL to Bax proteins, and a large reduction in pulmonary vascular permeability and myeloperoxidase (MPO) activity in comparison with WT mice. TLR4 mutant mice also displayed marked decreases in tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-2 (MIP-2) expression. Following intestinal I/R, phosporylation of p38 MAPK and activation of NF-κB and AP-1 were significantly inhibited in lung tissue from TLR4 mutant mice compared with WT controls. CONCLUSIONS: These data suggest that TLR4 plays an important role in the pathogenesis of intestinal I/R-induced acute lung injury and inflammation and that p38 kinase and NF-κB may be involved in TLR4 signaling-mediated lung inflammatory processes during intestinal I/R.

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.

Notoginsenoside R1 attenuates renal ischemia-reperfusion injury in rats.

Ischemia-reperfusion (I/R) injury of the kidney is a complex pathophysiological process and a major cause of acute renal failure. It has been shown that I/R injury is related to inflammatory responses and activation of apoptotic pathways. Inhibition of certain elements of inflammatory responses and apoptotic pathway seemed to ameliorate renal I/R injury. As an effective element of Panax notoginseng, NR1 has antioxidant, anti-inflammatory, antiapoptotic, and immune-stimulatory activities. Therefore, we speculate that NR1 can attenuate renal I/R injury. Ischemia-reperfusion injury was induced by renal pedicle ligation followed by reperfusion along with a contralateral nephrectomy. Male Sprague-Dawley rats were randomized to four groups: sham group, I/R control group, NR1-1 group (rats treated with NR1, 20 mg.kg.d) and NR1-2 group (rats treated with NR1, 40 mg.kg.d). All animals were killed 72 h after I/R induction. Blood and renal tissues were collected. Renal dysfunction was observed by the level of serum creatinine and histological evaluation. Apoptosis and inflammatory response in the tissue of kidney were detected mainly with molecular biological methods. NR1 attenuated I/R-induced renal dysfunction as indicated by the level of serum creatinine and histological evaluation. It prevented the I/R-induced increases in the levels of proinflammatory cytokine TNF-alpha, myeloperoxidase activity, phosphorylation of p38, and activation of nuclear factor kappaB with cell apoptosis in the kidney and enhanced expression of antiapoptosis cytokine bcl-2. Treatment with NR1 improves renal function after I/R associated with a significant reduction in cell apoptosis and inflammatory responses, which may be related to p38 and nuclear factor kappaB inhibition.

Factors affecting survival in adult patients with massive burns.

OBJECTIVE: To identify treatment-related factors associated with mortality in massively burned adult patients. METHODS: This retrospective cohort study examined survival outcomes at a burn unit of 54 beds and 10 burn ICU beds, totaling 900 admissions per year. The cases of 102 adult patients, admitted consecutively from January 1993 to October 2007, with massive burns (burn area>70% of the total body surface area, TBSA) were studied. Relevant variables were recorded from the initial injury and throughout the hospital course. Survival analysis, based on univariate and stepwise multivariate Cox proportional hazards regression, was performed to determine which variables predicted mortality. RESULTS: The overall mortality rate was 30.4%. Burn size, severe inhalation injury, full-thickness burns, serum creatinine levels, inotropic support, platelet counts<20,000 per mm3, sepsis and ventilator dependency were significantly associated with mortality as determined by univariate analysis. Only sepsis, ventilator dependency and platelet counts were significant independent predictors of mortality as determined by multivariate analysis. CONCLUSIONS: Sepsis, ventilator dependence (indicating severe respiratory complications), and low platelet counts (indicating thrombocytopenia) are associated with increased mortality risk in adult patients with massive burns. Methods should be sought to ameliorate these complications during treatment in burn-care units.

Angiotensin II induces type I collagen gene expression in human dermal fibroblasts through an AP-1/TGF-beta1-dependent pathway.

Angiotensin II is critically involved in skin wound healing, but the underlying mechanism remains unclear. This study investigated the effect of angiotensin II on type I collagen gene activation in human dermal fibroblasts and the possible mechanism involved. Angiotensin II stimulated the mRNA and protein expression of type I collagen and TGF-beta1. Effects were abolished by the angiotensin AT1 receptor antagonist ZD7155 but not by the AT2 blocker PD123319. Blockade of TGF-beta1 markedly inhibited angiotensin II-induced type I collagen gene expression. Activator protein-1 (AP-1) decoy ODNs transfection suppressed angiotensin II-induced TGF-beta1 expression, and also, diminished type I collagen expression. These data indicated that angiotensin II induces collagen gene activation in human dermal fibroblasts through an AT1-mediated AP-1/TGF-beta1 signaling pathway.

Suppressed acute phase response to LPS-induced hepatic injury in Smad3-deficient mice.

The generation of animals lacking Smad proteins has made it possible to explore the contribution of the TGF-beta-Smad signaling to immune activity in vivo. And there have been related issues actively pursued by many laboratories. Here we report that, in contrast to the markedly enhanced inflammatory response, Smad3 gene knockout (Smad3(ex8/ex8)) mice paradoxically show suppressed hepatic acute phase response to the injury induced by lipopolysaccharide (LPS) compared with wild-type mice, characterized by significantly weaker reaction of several typical acute phase proteins in mRNA level. The increase of positive acute phase proteins, e.g. alpha1-acid glycoprotein (alpha1-AGP), haptoglobin (HP) and C-reaction protein (CRP), and the decrease of negative acute phase proteins, including albumin (ALB) and transferrin (TRF), were both repressed according to the expression in liver estimated by optimized RT-PCR. Smad3(ex8/ex8) mice also exhibited lower survival rate as stimulated by LPS, which was probably on account of the suppressed acute phase response. These data are, to our knowledge, the first to implicate Smad3 in specific pathways of acute phase response in the liver.

Activation of p38 MAPK by reactive oxygen species is essential in a rat model of stress-induced gastric mucosal injury.

Stress ulceration is a common complication in critically ill patients and can result in significant upper gastrointestinal bleeding associated with a high morbidity and mortality. At present, little is known of the molecular mechanisms underlying the incidence of this type of gastric damage. In the present study, we investigated the temporal activation of the redox-sensitive p38 signaling transduction cascade and its roles in a well-defined experimental model of cold immobilization stress-induced gastric ulceration. Exposure of Sprague-Dawley rats to 6 h of cold immobilization stress led to a rapid activation of p38 in the gastric mucosa at as early as 15 min after stress, and this activation was maximal after 1.5 h of stress and still persisted until the end of stress. Selectively blocking p38 by pretreatment with SB 239063, a potent and selective p38 inhibitor, suppressed the stress-promoted TNF-alpha, IL-1beta, and CINC-1 production and then prevented the subsequent neutrophil infiltration, gastric mucosal epithelial necrosis and apoptosis, and the ulcerative lesions formation. Prior administration of the free radical scavengers, tempol and N-acetyl-L-cysteine, abolished the stress induction of p38 activation and the resulting mucosal inflammation and gastric injury. These results demonstrate that reactive oxygen species-mediated p38 activation plays an essential role in the pathogenesis of stress-induced gastric inflammatory damage in the rat model of cold immobilization stress. Our findings suggested that inhibition of p38 activation might be a potential strategy for the prophylaxis and treatment of stress ulceration.