Therapeutic effectiveness of gamma-globulin on experimental burns

Experiments on rabbits were made to examine excretory-absorption liver function and the blood kallikrein-kinin system after thermal burn and treatment with gamma-globulin immune to burn skin toxin. Immunotherapy leads to a more rapid and effective recovery of the functional indicators in the burnt animals than in burns without or with the treatment by nonimmune preparations. It was demonstrated that specific detoxification plays an important role in multiple modality treatment of burn disease.     

Acute effects of combined burn and smoke inhalation injury on carboxyhemoglobin formation, tissue oxygenation, and cardiac performance

The objective of this study was to determine the relationship between carboxyhemoglobin (COHb) formation, global oxygen transport, and cardiac performance in the acute phase of combined burn and smoke inhalation injury. Following a third degree burn of 20% of the total body surface area, adult sheep were subjected to cotton smoke (4x12 breaths) according to an established protocol. Compared with baseline (BL), the burn injury led to an immediate and sustained COHb-independent depression in myocardial contractility. Despite a progressive increase in COHb formation, up to a maximum of 78+/-3% (P < 0.001 vs BL), smoke inhalation did not further impair these hemodynamic changes. This study demonstrated that in the early stage of combined burn and smoke inhalation injury, the depression in cardiac function is basically triggered by the burn injury, whereas COHb generation secondary to cotton smoke exposure primarily contributes to pulmonary shunting.     

Role of increased peripheral vascular resistance in burn shock]

The effect of lethal burn injury on the parameters of hemodynamics and respiration was investigated in intact rabbits and those with disconnected aortal and sinocarotid reflexogenic zones. The rabbits of both groups demonstrated similar changes in cardiac output and total oxygen consumption. Unlike intact animals, the burn in rabbits with disconnected reflexogenic zones did not lead to a marked increase in the peripheral vascular resistance. Accordingly, the systemic arterial blood pressure in them fell to a considerably greater extent than that in the intact animals. The life span of the rabbits exposed to burns was less as compared to the intact ones. A reflex compensatory nature of the increased peripheral vascular resistance in burn shock is suggested.     

Properties of Staphylococcus aureus in case of the unfavorable course of burn infection

Clinical and microbiological study of wound discharge from 35 patients demonstrated a relationship between biological properties of S. aureus, the causative agent of burn infection, and the course of the infected burn trauma. The prognostic importance of the antioxidant properties of these staphylococci was established: in cases of the unfavorable course of the burn process they showed essentially greater resistance to peroxinitrite and higher superoxide dismutase activity in comparison with the cultures isolated from patients with uncomplicated wound infection.     

Oxidants and the pathophysiology of burn and smoke inhalation injury.

A skin burn is a common traumatic injury that results in both local tissue damage and a systemic mediator-induced response. There is evidence of both local and systemic oxidant changes manifested by lipid peroxidation in animal burn models and also in burned man. Both increased xanthine oxidase and neutrophil activation appear to be the oxidant sources. Animal studies have also demonstrated decreased burn edema, and also decreased distant organ dysfunction with the use of antioxidants, suggesting a cause-and-effect relationship, which needs to be tested in man. Smoke inhalation injury, a chemical injury to the airways caused by incomplete products of combustion, is frequently seen in conjunction with a body burn. Lipid peroxidation, both in lung and in distant organs, is also seen with this injury. The combined body burn and smoke inhalation injury lead to a marked increase in mortality rate and also an increase in the degree of generalized oxidant release and lipid peroxidation. Although data in man are limited, the available information, along with that from animal research on burns and smoke inhalation, indicates oxidants may well play a key role, and antioxidants may be of clinical therapeutic use.     

Anterior neck reconstruction with pre-expanded free groin and scapular flaps

To improve aesthetic and functional outcomes in the reconstruction of severe anterior neck burn deformities and to reduce donor-site morbidity, pre-expansion of free-flap donor sites was performed in eight patients. In the first stage of reconstruction, the tissue expander was placed and gradually inflated over a period of 6 weeks. In the second stage, the anterior neck scar was resected up to the limits of the aesthetic unit of the neck, radical release of neck contracture was achieved by transection of contracted platysma muscle, and immediate coverage with a pre-expanded groin or scapular free flap was performed. The early postoperative course was uneventful. Physical therapy was started 1 week after the reconstruction. Long-term follow-up (mean, 4 years) of patients who underwent reconstruction of extensive neck burn deformities demonstrated good aesthetic and functional results. The advantages and drawbacks of using pre-expanded free flaps in the treatment of neck burn contractures are discussed.     

Pathomorphology of the nodose ganglia of the vagus nerves in burns

Pathomorphology of ganglion nodosum was studied by means of neurohistological methods in 65 dead patients during different periods of burn disease and demonstrated a definite dynamic of structural modifications. In period of burn shock there were discovered dystrophic changes and necrosis of neuron separate groups, varicose thickness of a myelin sheath, in period of toxemia hypertrophied neurons with thick axons predominated, in period of septic toxemia and burn exhaustion predominated atrophic changes, necrotic neurons and grain-blockage disintegration of nervous fibres.     

烧伤患者创面与环境中病原微生物耐药性及相关性的研究

了解烧伤科病人创面感染、环境监测的主要致病菌及其耐药性,探讨二者的关系。运用Sceptor鉴定仪对检出菌进行鉴定,K-B法对主要致病菌进行药敏试验。结果表明,引起烧伤创面感染的主要致病菌为不动杆菌(24.6%)、MRSA(19.8%)、绿脓杆菌(16.7%),烧伤科病房环境分离出的主要细菌为不动杆菌(17.7%)、绿脓杆菌(17.7%)、MRSA(13.3%),创面分离的致病菌与环境检出的细菌具有一定的相关性。特别是MRSA、MRSE,从创面与环境二者分离出的菌株具有相似的抗菌谱,这说明环境因素特别是医陪护人员的手表、物表成为该菌在烧伤病房传播的重要环节。     

Disorder of the phagocytosis process in alveolar macrophages in thermal injury

Bacteriological assay, cytochemical studies of succinate and malate dehydrogenases, acid phosphatase, glycogen and lipids, as well as electron microscopy were used in experiments on 75 rabbits to examine over time phagocytosis of alveolar macrophages and some mechanisms of its disturbance after burn trauma. It was established that the phagocytic function of alveolar macrophages gets disturbed shortly after trauma, remaining depressed up to the time of convalescence. It was demonstrated that the mechanism by which phagocytic function gets disturbed differs with time following trauma. Primary depression of phagocytosis occurs immediately after burn. At the height of burn disease the cells develop an energy deficient state, whereas the time of convalescence is marked by the emergence of poorly differentiated forms of macrophages having the reduced phagocyte capacity.     

Improvement in burn wound infection and survival with antimicrobial peptide D2A21 (Demegel)

Naturally occurring antimicrobial peptides have been discovered in both plants and animals. Many of these peptides demonstrate impaired activity or cytotoxicity when applied exogenously. Synthetically engineered antimicrobial peptides have been designed to increase potency and activity against bacteria and fungus yet remain noncytotoxic. The antimicrobial peptide D2A21 (Demegel) has already demonstrated significant activity in vitro against many common hospital pathogens. The purpose of this study was to evaluate the effects of D2A21 in an in vivo infected burn-wound model, examining both quantitative cultures of the wound and survival of the animal. Forty-four Wistar rats were subjected to a 23 percent total body surface area scald burn. Pseudomonas aeruginosa was administered topically with 108 organisms and wounds were then evaluated at day 1, 2, or 3 for eschar and subeschar muscle quantitative culture. The experimental group was treated daily with 1.5% topical D2A21. The control group was treated with control gel. A second group of Wistar rats (n = 14) were burned and given a 107 inoculum of the same Pseudomonas and evaluated to 14 days for survival and weight changes. This group was subdivided into rats receiving either topical D2A21 or control base daily. The quantitative biopsy results demonstrated that D2A21-treated wounds had no bacterial growth in burn eschar at day 2 or 3, whereas control animals demonstrated growth at greater than 105 organisms by day 2. Subeschar muscle cultures also demonstrated significantly less bacterial invasion compared with controls on each day tested. D2A21-treated animals had an 85.7 percent survival compared with 0 percent survival in controls. Furthermore, the D2A21-treated groups demonstrated maintenance of body weights, whereas controls had significant weight loss with time. In conclusion, D2A21 demonstrates significant antibacterial activity against Pseudomonas, sterilizing burn eschar and decreasing subeschar bacterial load, allowing for a markedly significant improvement in survival in this infected burn-wound model.     

Burn injury suppresses human dermal dendritic cell and Langerhans cell function

Human skin contains epidermal Langerhans cells (LCs) and dermal dendritic cells (DCs) that are key players in induction of adaptive immunity upon infection. After major burn injury, suppressed adaptive immunity has been observed in patients. Here we demonstrate that burn injury affects adaptive immunity by altering both epidermal LC and dermal DC functions. We developed a human ex vivo burn injury model to study the function of DCs in thermally injured skin. No differences were observed in the capacity of both LCs and dermal DCs to migrate out of burned skin compared to unburned skin. Similarly, expression levels of co-stimulatory molecules were unaltered. Notably, we observed a strong reduction of T cell activation induced by antigen presenting cell (APC) subsets that migrated from burned skin through soluble burn factors. Further analyses demonstrated that both epidermal LCs and dermal DCs have a decreased T cell stimulatory capacity after burn injury. Restoring the T cell stimulatory capacity of DC subsets might improve tissue regeneration in patients with burn wounds.     

Macrophage migration inhibitory factor mediates late cardiac dysfunction after burn injury

We have recently demonstrated that macrophage migration inhibitory factor (MIF) is a myocardial depressant protein and that MIF mediates late, prolonged cardiac dysfunction after endotoxin challenge in mice. Because many factors, including endotoxin, have been implicated in the pathogenesis of cardiac dysfunction after burn injury, we tested the hypothesis that MIF might also be the mediator of prolonged cardiac dysfunction in this model. At 4 h after 40% total body surface area burn in anesthetized mice, serum MIF levels increased significantly compared with baseline (2.2-fold). This increase was accompanied by a significant decrease in cardiac tissue MIF levels (2.1-fold decrease compared with controls). This pattern was consistent with MIF release from preformed cytoplasmic stores in the heart and other organs. To determine whether MIF mediates cardiac dysfunction after burn injury, mice were pretreated with anti-MIF neutralizing monoclonal antibodies or isotype control antibodies. Beginning 4 h after burn injury (and continuing through 48 h), burned mice demonstrated a significantly depressed left ventricular shortening fraction of 38.6 +/- 1.8%, compared with the normal controls (56.0 +/- 2.6%). Mice treated with anti-MIF displayed an initial depression of cardiac function similar to nontreated animals but then showed rapid restoration of cardiac function with complete recovery by 24 h, which persisted for the duration of the protocol. This study is the first to demonstrate that MIF mediates late, prolonged cardiac dysfunction after burn injury and suggests that MIF blockade should be considered a therapeutic target for the treatment of burn injury.     

The effect of N-stearoylethanolamine on free amino acid levels in plasma and liver of rats with an experimental burn

The effect of an endocannabinoid congener, N-stearoylethanolamine (NSE), on the content of plasma and liver pools of free amino acids (AA) was studied in burned rats. After application of a thermal skin burn (stage III) animals perorally received an aqueous suspension of NSE (10 mg/kg of body weight) during 7 days or were treated with the aqueous NSE suspension (10 mg/ml) applied onto the burn wound, or received a combined treatment. It has been originally demonstrated for the first time, that the treatment of burned rats with NSE prevented the decrease in total AA concentration in blood plasma and the increase in hepatic AA concentration due to modulation in concentrations of glycogenic AA. In burned animals the ratio of plasma and liver homogenate Phe/Tyr and Gly/Val increased while the Fischer ratio (Ile+Leu+Val/Phe+Tyr) decreased, and after the treatment with NSE these parameters remained at the level of intact animals. These data demonstrate that NSE possesses adaptogenic properties, and it is involved in the organism response to the burn. This prevents changes in blood plasma and hepatic pools of free AA of NSE-treated rats with the burn wound compared with untreated animals.     

Structural and enzymatic disorganization of biological membranes in rat liver cells in thermal burns

Permeability of hepatocyte cell membrane was studied from the release into blood of hepatospecific enzymes and from 5'-nucleotidase activity in plasma membranes. A study was also made of membrane permeability of mitochondria, lysosomes and microsomes in liver cells of burnt rats from the level of non-sedimented activity and activity of malate dehydrogenase, succinate dehydrogenase, cathepsin D and glucose-6-phosphatase in appropriate organelles. Permeability of cell and lysosomal membranes was demonstrated to be disordered within the first hours after burn. One day after burn generalized disturbance of membrane permeability in the cell was observed, followed by the release into cytosol of organelles template enzymes and a decrease in the activity of membrane-bound enzymes in these organelles. The alterations persisted during 7 days of observation.     

Heme oxygenase-1 protects against neutrophil-mediated intestinal damage by down-regulation of neutrophil p47phox and p67phox activity and O2- production in a two-hit model of alcohol intoxication and burn injury

Heme oxygenase-1 (HO-1) has been demonstrated to protect against tissue injury. Furthermore, HO-1 is also shown to be antioxidant. Our recent findings indicate that acute alcohol (EtOH) intoxication exacerbates postburn intestinal and lung tissue damage, and this was found to be neutrophil dependent. Because neutrophil-mediated tissue injury involves the release of superoxide anions (O(2)(-)), the present study examined the role of HO-1 in neutrophil O(2)(-) production following EtOH and burn injury. Furthermore, we investigated whether HO-1 antioxidant properties are mediated via modulation of p47(phox) and/or p67(phox) proteins. Male rats (approximately 250 g) were gavaged with EtOH to achieve a blood EtOH level of approximately 100 mg/dL before burn or sham injury (approximately 12.5% total body surface area). Some rats were treated with HO-1 activator cobalt protoporphyrin IX chloride (Copp; 25 mg/kg body weight) at the time of injury. On day 1 after injury, we found that EtOH combined with burn injury significantly increased neutrophil O(2)(-) production and p47(phox) and p67(phox) activation and decreased caspase-3 activity and apoptosis. This was accompanied with a decrease in neutrophil HO-1 levels. The treatment of animals with HO-1 activator Copp normalized neutrophil HO-1, O(2)(-), p47(phox), and p67(phox) following EtOH and burn injury. The expression of caspase-3, however, was further decreased in Copp-treated sham and EtOH plus burn groups. Moreover, Copp treatment also prevented the increase in intestinal edema and permeability following EtOH and burn injury. Altogether, these findings provide a new insight into the mechanism by which HO-1 regulates neutrophil O(2)(-) production and protect the intestine from damage following EtOH and burn injury.     

Melatonin reduces oxidative damage to skin and normalizes blood coagulation in a rat model of thermal injury

This study was designed to determine the effect of melatonin treatment on the glutathione (GSH) and lipid peroxidation (LPO) levels in the skin as well as prothrombin time (PT) and fibrin degradation products (FDPs) in the blood of rats with thermal injury. Under ether anaesthesia, the shaved dorsum of the rats was exposed to 90 degrees C bath for 10 s to induce burn injury. Rats were decapitated either 3 or 24 hours after burn injury. Melatonin (10 mg/kg) was administered i.p. immediately after burn injury to same animals. In the 24 hour burn group, melatonin injections were repeated for two more occasions 8 and 16 h after burn injury. In the control group the same protocol was applied except that the dorsum was exposed to a 25 degrees C water bath for 10 s. Severe skin scald injury (30% of total body surface area) caused a significant decrease in PT at post burn 3 and 24 hours. FDPs was not increased at post burn 3 hour but was significantly increased at post burn 24 hour. GSH levels were significantly depressed at post burn 3 hour but were not changed at post burn 24 hour. LPO levels were significantly increased both at post burn 3 and 24 hours. Skin protein levels were significantly reduced at post burn 24 hour as evidenced by electrophoresis. Treatment of rats with melatonin normalized PT levels both at post burn 3 and 24 hours. FDP decreased at post burn 24 hour due to melatonin treatment. GSH levels significantly increased as a result of melatonin treatment both at post burn 3 and 24 hours melatonin treatment. LPO levels were not changed by melatonin at post burn 3 hour; however, the melatonin significantly decreased LPO values at post burn 24 hours. In conclusion, exogenously administered melatonin reduced skin oxidant damage and normalized the activated blood coagulation induced by thermal trauma.     

Prophylactic treatment with fms-like tyrosine kinase-3 ligand after burn injury enhances global immune responses to infection

Severely burned patients are susceptible to infections with opportunistic organisms due to altered immune responses and frequent wound contamination. Immunomodulation to enhance systemic and local responses to wound infections may be protective after burn injury. We previously demonstrated that pretreatments with fms-like tyrosine kinase-3 (Flt3) ligand (Flt3L), a dendritic cell growth factor, increase the resistance of mice to a subsequent burn injury and wound infection by a dendritic cell-dependent mechanism. This study was designed to test the hypothesis that Flt3L administration after burn injury decreases susceptibility to wound infections by enhancing global immune cell activation. Mice were treated with Flt3L after burn injury and examined for survival, wound and systemic bacterial clearance, and immune cell activation after wound inoculation with Pseudomonas aeruginosa. To gain insight into the local effects of Flt3L at the burn wound, localization of Langerhans cells was examined. Mice treated with Flt3L had significantly greater numbers of CD25-expressing T cells and CD69-expressing T and B cells, neutrophils, and macrophages after, but not before, infection. Overall leukocyte apoptosis in response to infection was decreased with Flt3L treatment. Survival and local and systemic bacterial clearance were enhanced by Flt3L. Langerhans cells appeared in the dermis of skin bordering the burn wound, and further increased in response to wound infection. Flt3L augmented the appearance of Langerhans cells in response to both injury and infection. These data suggest that dendritic cell enhancement by Flt3L treatments after burn injury protects against opportunistic infections through promotion of local and systemic immune responses to infection.     

Influence of Liposomal Compositions Containing AFP and GCSF Recombinant Human Proteins on Mice Skin Radiation Burn according to Clinical Indicators and Indices of Skin Stem Cells

Biology Bulletin - Using a IIIA radiation skin burn model in CD1 mice, we demonstrated that transdermal application of liposomes containing rhAFP; liposomes containing rhGCSF; and liposomes...