Ulinastatin improves pulmonary function in severe burn-induced acute lung injury by attenuating inflammatory response.

BACKGROUND: Acute systemic inflammatory response to severe skin burn injury mediates burn-induced acute lung injury. Ulinastatin is potentially an effective intervention, because it attenuates the systemic inflammatory response induced by endotoxin and improves myocardial function during ischemic shock and reperfusion. METHODS: Rats received full-thickness burn wounds to 30% total body surface area followed by delayed resuscitation. The treatment group received 50,000 U/kg of ulinastatin and the burn group was given vehicle only. A sham group was not burned but otherwise was treated identically. After killing, blood and lung samples were harvested for histology and measurement of inflammatory mediators. RESULTS: Administration of ulinastatin significantly decreased the mRNA and protein levels of tumor necrosis factor-alpha, interleukin-1ß, -6, and -8 both locally and systemically in burn-injured rats. The secretion of neutrophil elastase and myeloperoxidase in the lung and the expression of intercellular adhesion molecule-1 on the surface of lung epithelium were inhibited by ulinastatin. Ulinastatin also reduced the increase in pulmonary microvascular permeability. Consistent with these findings, ulinastatin ameliorated the lung edema and pulmonary oxygenation in burn-injured rats. CONCLUSIONS: These results indicate that the inhibitory effects of ulinastatin on inflammatory mediator production, neutrophil activation, and microvascular permeability are associated with the recovery of pulmonary functions in severe burn-induced acute lung injury and suggest that ulinastatin may serve as a potential therapeutic administration in critical burn care.

[Treatment of extensive cervicomandibular scar in children and adolescent patients with bilateral expanded scapular flaps: report of 7 consecutive cases].

PURPOSE: To explore the feasibility of applying bilateral free expanded scapular flaps to treat extensive cervicomandibular scar in children and adolescents. METHODS: This study reviewed 7 children and adolescent patients who received bilateral expanded scapular flaps to treat extensive cervicomandibular scars in the Pediatric Plastic Surgery Ward from August 2018 to December 2020. The scars in all patients involved neck, mandible, and anterior chest. The cervical scars involved the anterior neck and one or both sides of the lateral neck, and there were varying degrees of cervical dysfunction and mandibular dysplasia. The operation was completed into two stages. In the first stage, the expanded circumflex scapular artery perforator flaps were designed on both sides of the back and soft tissue expanders were implanted. The expansion process lasted for 6-14 months. In the second stage, the scar tissue was removed and contracture was released, and the expanded flaps were harvested. The cervical wound was repaired with free flap transplantation by anastomosing the facial artery and vein with the circumflex scapular artery and vein. The donor sites were closed directly. RESULTS: In this series of 7 patients, one patient had poorly healed incision after the expander was implanted. One expanded flap ruptured before the second-stage surgery, which was successfully treated by secondary surgery. One patient had expansion problem due to the blockage of the internally placed injection bottle, which was treated by placing the injection bottle externally. One patient developed a small area of ischemic necrosis at the distal end of the flap after transplantation, which was treated conservatively with dressing change. The postoperative follow-up was 6 months to 2 years. The cervico-mandibular angle restored to normal range, the cervical extension, flexion, and rotation were significantly improved. Two patients underwent flap thinning and scar releasing. CONCLUSIONS: The route of the circumflex scapular artery is constant. Bilateral expanded scapular flap transplantation can be used to repair extensive cervicomandibular scar in children and adolescent patients. The flap donor site is concealed and secondary damage is minimal.

Reactive Oxygen Species Mediated Prostaglandin E2 Contributes to Acute Response of Epithelial Injury.

Reactive oxygen species (ROS) generated after tissue injury play a crucial role during wound healing through initiating acute inflammation, clarifying infection and dead tissue, and mediating various intracellular signal transduction. Prostaglandin E2 (PGE2) has been identified as one of the major factors responsible for inflammation and tissue repair. In this study, we tested our hypothesis that ROS produced by damaged human keratinocytes induces the synthesis of PGE2. In vitro epithelial wounding model was used to observe the production of ROS and secretion of PGE2 as well as the involved signal pathway. The mechanical injury caused the rapid production of ROS in in vitro cultured keratinocytes, which was significantly blocked by an inhibitor of nicotinamide adenine dinucleotide phosphate oxidase. The increased intracellular ROS caused by mechanical injury stimulates PGE2 production in a time-dependent manner via the activation of cyclooxygenase-2 (COX-2), which was stimulated by phosphorylation of extracellular signal-regulated protein kinase (ERK). These results indicate ROS-induced ERK activation leading to the activation of COX-2 and the synthesis of PGE2 in human keratinocytes responding to mechanical injury in the acute phase.

NADPH oxidase 1 and its derived reactive oxygen species mediated tissue injury and repair.

Reactive oxygen species are mostly viewed to cause oxidative damage to various cells and induce organ dysfunction after ischemia-reperfusion injury. However, they are also considered as crucial molecules for cellular signal transduction in biology. NADPH oxidase, whose only function is reactive oxygen species production, has been extensively investigated in many cell types especially phagocytes. The deficiency of NADPH oxidase extends the process of inflammation and delays tissue repair, which causes chronic granulomatous disease in patients. NADPH oxidase 1, one member of the NADPH oxidase family, is not only constitutively expressed in a variety of tissues, but also induced to increase expression in both mRNA and protein levels under many circumstances. NADPH oxidase 1 and its derived reactive oxygen species are suggested to be able to regulate inflammation reaction, cell proliferation and migration, and extracellular matrix synthesis, which contribute to the processes of tissue injury and repair.

Enzyme activated photodynamic therapy for methicillin-resistant Staphylococcus aureus infection both inv itro and in vivo.

In recent years, methicillin-resistant Staphylococcus aureus (MRSA) has become one of the most common multi-drug resistant bacteria in both hospital and community. The aim of this study is to investigate the selective inhibition of MRSA by a modified photosensitizer (LAEtNBS) in vitro and the efficacy of MRSA infection treatment by photodynamic therapy (PDT) with LAEtNBS in vivo. LAEtNBS was synthesized by adding a cationic photosensitizer molecule (EtNBS-COOH) and a quencher molecule to two side chains of cephalosporin, which was then shown to have similar absorption and emission wavelengths with EtNBS-COOH, but suppressed yields of fluorescence quantum and singlet oxygen. The selective inactivation and less phototoxicity of LAEtNBS, compared to that of EtNBS-COOH, were assessed and confirmed by conducting PDT to two Staphylococcus aureus strains and human skin cells at a fluence of 15 J/cm(2) with 640±10 nm LED light. Furthermore, using mouse skin wound model infected with 10(8) CFU of MRSA, we found that both LAEtNBS and EtNBS-COOH were able to treat MRSA infection and enhance wound repair. However, there was no significant difference in the two photosensitizers that might be due to the environment in vivo. Modification of the photosensitizer will be very beneficial for developing new strategies to treat drug resistant bacterial infection with less harm to host tissue.

Antimicrobial photodynamic therapy for methicillin-resistant Staphylococcus aureus infection.

Nowadays methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common multidrug resistant bacteria both in hospitals and in the community. In the last two decades, there has been growing concern about the increasing resistance to MRSA of the most potent antibiotic glycopeptides. MRSA infection poses a serious problem for physicians and their patients. Photosensitizer-mediated antimicrobial photodynamic therapy (PDT) appears to be a promising and innovative approach for treating multidrug resistant infection. In spite of encouraging reports of the use of antimicrobial PDT to inactivate MRSA in large in vitro studies, there are only few in vivo studies. Therefore, applying PDT in the clinic for MRSA infection is still a long way off.

Hydrogen-rich saline protects against acute lung injury induced by extensive burn in rat model.

Hydrogen has been reported to selectively quench detrimental reactive oxygen species, particularly hydroxyl radical, and to prevent myocardial or hepatic ischemia/reperfusion injury in multiple models. The aim of this study is to investigate whether hydrogen protects against severe burn-induced acute lung injury in rats. Rats were divided into four groups: sham plus normal saline, burn injury plus normal saline, burn injury plus hydrogen-rich saline, and burn injury plus edaravone. Animals were given full-thickness burn wounds (30% TBSA) using boiling water, except the sham group that was treated with room temperature water. The rats in hydrogen group received 5 ml/kg of hydrogen-rich saline, sham and burn controls obtained the same amount of saline, and the edaravone group was treated with 9 mg/kg of edaravone in saline. Lactated Ringer's solution was given at 6 hours postburn. The lungs were harvested 12 hours postburn for laboratory investigations. Severe burns with delayed resuscitation rapidly caused lung edema and impaired oxygenation in rats. These dysfunctions were ameliorated by administration of hydrogen-rich saline or edaravone. When compared with the burn injury plus normal saline group, hydrogen-rich saline or edaravone group significantly attenuated the pulmonary oxidative products, such as malondialdehyde, carbonyl, and 8-hydroxy-2'-deoxyguanosine. Furthermore, administration of hydrogen-rich saline or edaravone dramatically reduced the pulmonary levels of pulmonary inflammation mediators and myeloperoxidase. Intraperitoneal administration of hydrogen-rich saline improves pulmonary function by reducing oxidative stress and inflammatory response in severe burn-induced acute lung injury.