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Background: Clinically, the condition of skeletal muscle injury is the key to the process of high voltage electrical burn (HVEB) wound repair. The aim of this study was to identify the potential mechanisms and intervention targets of skeletal muscle injury after HVEB., Methods: A skeletal muscle injury model in SD rats with HVEB was made. Pathological examination and transcriptome sequencing of injured skeletal muscles were performed, and the expression levels of key proteins and genes in related signaling pathways were verified., Results: Skeletal muscle injury was progressively aggravated within 48 h, then the injury was gradually repaired with scar formation occurring within 1 week. The mechanism of skeletal muscle injury is complex and varied, and ferroptosis is one of the mechanisms. The ferrous iron content in the injured skeletal muscle tissue of model rats increased significantly at 24 h after injury. After 24 h, damage to injured skeletal muscle tissue could be alleviated by increasing iron storage and blocking lysosomal phagocytosis of autophagy., Conclusions: Skeletal muscle injury caused by HVEB is characterized by adjacent endangered tissue progression after injury. Ferroptosis is involved in the mechanism of HVEB, and iron metabolism-related proteins may be potential targets for preventing progressive skeletal muscle injury., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Treatment options for liver metastases (primarily colorectal cancer) are limited by high recurrence rates and persistent tumor progression. Surgical approaches to management of these metastases typically use heat energy including electrocautery, argon beam coagulation, thermal ablation of surgical margins for hemostasis, and preemptive thermal ablation to prevent bleeding or to effect tumor destruction. Based on high rates of local recurrence, these studies assess whether local effects of hepatic thermal injury (HTI) might contribute to poor outcomes by promoting a hepatic microenvironment favorable for tumor engraftment or progression due to induction of procancer cytokines and deleterious immune infiltrates at the site of thermal injury. To test this hypothesis, an immunocompetent mouse model was developed wherein HTI was combined with concomitant intrasplenic injection of cells from a well-characterized MC38 colon carcinoma cell line. In this model, HTI resulted in a significant increase in engraftment and progression of MC38 tumors at the site of thermal injury. Furthermore, there were local increases in expression of messenger ribonucleic acid (mRNA) for hypoxia-inducible factor-1α (HIF1α), arginase-1, and vascular endothelial growth factor α and activation changes in recruited macrophages at the HTI site but not in untreated liver tissue. Inhibition of HIF1α following HTI significantly reduced discreet hepatic tumor development ( P = 0.03). Taken together, these findings demonstrate that HTI creates a favorable local environment that is associated with protumorigenic activation of macrophages and implantation of circulating tumors. Discrete targeting of HIF1α signaling or inhibiting macrophages offers potential strategies for improving the outcome of surgical management of hepatic metastases where HTI is used.

Background: The decrease of the left ventricular ejection fraction (LVEF) as consequence of a ventricular dysfunction is reported in cardiac alterations secondary to electrical injury. The focused cardiac ultrasound (FoCUS) helps to complete the clinical examination because it allows a faster non-invasive evaluation, and provides information that contributes to make better therapeutic decisions, especially those for patients in critical condition. The objective of this study was to explore the utility of creatine phosphokinase MB (CPK-MB) as a diagnostic tool of myocardial dysfunction in patients from 6 to 18 years old with electrical burn., Methods: From November 2018 to August 2019, we conducted a transversal analytic study of 10 children with electric burn (6 to 18 years of age), in whom the percentage of LVEF was obtained through the FoCUS protocol in the first 24 hours after injury., Results: We found 10 cases of electrical burn injury, eight males and two females, with an average of 13 years of age. Eighty percent of these cases showed a slight decrease in LVEF (45-59%). When performing the FoCUS protocol, myocardial hypokinesia was reported in seven patients. We observed a moderate correlation between LVEF and CPK-MB levels (r = -0.671), and no correlation between LVEF and body surface area affected by the electrical burn., Conclusions: The cardiac ultrasound influences decision making to improve the prognosis of these patients., (Copyright: © 2020 Permanyer.)

Severe burn injury results in systemic disruption of metabolic regulations and impaired cardiac function. Restoration of hemodynamic homeostasis utilizing intravenous (IV) fluids is critical for acute care of the burn victim. However, the effects of burns and resuscitation on cardiomyocyte mitochondria are currently unknown. The purpose of this study is to determine cardiac mitochondrial function in a swine burn model with subsequent resuscitation using either crystalloids or colloids. Anesthetized Yorkshire swine ( n = 23) sustained 40% total body surface area burns and received IV crystalloids ( n = 11) or colloids ( n = 12) after recovery from anesthesia. Non-burned swine served as controls ( n = 9). After euthanasia at 48 h, heart tissues were harvested, permeabilized, and analyzed by high-resolution respirometry. Citrate synthase (CS) activity was measured, and Western blots were performed to quantify proteins associated with mitochondrial fusion (OPA1), fission (FIS1), and mitophagy (PINK1). There were no differences in state 2 respiration or maximal oxidative phosphorylation. Coupled complex 1 respiration decreased, while uncoupled state 4 O and complex II increased significantly due to burn injury, particularly in animals receiving colloids ( P < 0.05). CS activity and electron transfer coupling efficiency were significantly lower in burned animals, particularly with colloid treatment ( P < 0.05). Protein analysis revealed increased FIS1 but no differences in mitophagy in cardiac tissue from colloid-treated compared with crystalloid-treated swine. Taken together, severe burns alter mitochondrial respiration in heart tissue, which may be exacerbated by early IV resuscitation with colloids. Early IV burn resuscitation with colloids may require close hemodynamic observation. Mitochondrial stabilizing agents incorporated into resuscitation fluids may help the hemodynamic response to burn injury.

Introduction: Electrical burns cause significant morbidity and mortality worldwide. Here we measured changes in levels of serum oxidative stress and telomerase in children suffering from high-voltage electrical burn (HVEB) injuries and other burns and the significance of these parameters in terms of amputation., Materials and Methods: After obtaining approval from our ethics committee for this prospective study, we formed three groups: a group of 18 children with HVEBs, a group of 18 children with thermal burns, and a control group. All children were 1-16 years of age. The HVEB group was divided into HVEB-WA (without amputation) and HVEB-A (with amputation) subgroups. Serum malondialdehyde (MDA) level, total antioxidant capacity (TAC), total oxidant capacity (TOC), glutathione (GSH) level, and telomerase level were measured and compared among the groups., Results: The patients differed in terms of demographics. The healing time of the HVEB group was longer than that of the thermal burn group, and the oxidative stress indicators of the HVEB group remained higher for longer. The mean oxidative stress indices in the HVEB-A group were higher than those in the HVEB-WA group and remained elevated for longer., Conclusion: HVEBs are more destructive than thermal burns; damage may progress over time, and healing takes longer. Healing can be followed biochemically by measuring levels of oxidative stress indicators. Indications for amputation, if not initially obvious, can be predicted by evaluating these indicators, affording therapeutic advantages., (Copyright © 2018 Elsevier Ltd and ISBI. All rights reserved.)

Background: Electric burn patients usually suffer permanent injury and sequelae. Salvage of the zone of stasis is an important topic in the treatment of burn patients. N-Acetylcysteine (NAC), as an antioxidant, has effect on the saving zone of stasis and extensive rhabdomyolisis. The aim of this study was therefore to evaluate the effect of oral NAC on tissue destruction indicators in an electric burn rat model., Material and Methods: An experimental study was conducted with thirty six male Wistar albino rats divided into 2 groups. Group A (n=18) and group B (n=18) were electrical burn injury groups without and with NAC therapy, respectively. The extent of burn wounds were evaluated by planimetry using a digital wound measuring device. Blood samples were obtained to analyze creatine kinase (CK) levels as a marker of extensive rhabdomiolysis on the first hour after electric injury (baseline) and on the 7th day to see the antioxidant effect of NAC., Results: A significant decrease in tissue destruction was seen by the necrotic area on day 7 in the NAC therapy group compared to the control group (mean 2.26±1.05cm 2 versus mean 7.12±3.30cm 2 respectively; p=0.001), which was confirmed by the level of serum CK (day 7: group A, mean 140±51U/L versus Group B, mean 102±6U/L; p=0.007)., Conclusion: A decrease in electric burn necrotic area and tissue damage in the group using NAC treatment was demonstrated. NAC might have a beneficial effect in the treatment of electrical burns. Further experimental and clinical studies with NAC treatment are necessary to confirm these results., (Copyright © 2018 Elsevier Ltd and ISBI. All rights reserved.)

Rapid repair of vascular injury is an important prognostic factor for electrical burns. This repair is achieved mainly via stromal cell-derived factor (SDF)-1α promoting the mobilization, chemotaxis, homing, and targeted differentiation of bone marrow mesenchymal stem cells (BMSCs) into endothelial cells. Forming a concentration gradient from the site of local damage in the circulation is essential to the role of SDF-1α. In a previous study, we developed reactive oxygen species (ROS)-sensitive PPADT nanoparticles containing SDF-1α that could degrade in response to high concentration of ROS in tissue lesions, achieving the goal of targeted SDF-1α release. In the current study, a rat vascular injury model of electrical burns was used to evaluate the effects of targeted release of SDF-1α using PPADT nanoparticles on the chemotaxis of BMSCs and the repair of vascular injury. Continuous exposure to 220 V for 6 s could damage rat vascular endothelial cells, strip off the inner layer, significantly elevate the local level of ROS, and decrease the level of SDF-1α. After injection of Cy5-labeled SDF-1α-PPADT nanoparticles, the distribution of Cy5 fluorescence suggested that SDF-1α was distributed primarily at the injury site, and the local SDF-1α levels increased significantly. Seven days after injury with nanoparticles injection, aggregation of exogenous green fluorescent protein-labeled BMSCs at the injury site was observed. Ten days after injury, the endothelial cell arrangement was better organized and continuous, with relatively intact vascular morphology and more blood vessels. These results showed that SDF-1α-PPADT nanoparticles targeted the SDF-1α release at the site of injury, directing BMSC chemotaxis and homing, thereby promoting vascular repair in response to electrical burns.

Volume resuscitation of patients with high-voltage electrical injuries (>1000 V) is a more complex challenge than standard burn resuscitation. High voltages penetrate deep tissues. These deep injuries are not accounted for in resuscitation formulae dependent on percentage of cutaneous burn. Myonecrosis occurring from direct electrical injury and secondary compartment syndromes can result in rhabdomyolysis, compromising renal function and urine output. Urine output is the primary end point, with a goal of 1 mL/kg/h for adult patients with high-voltage electrical injuries. As such, secondary resuscitation end points of laboratory values, such as lactate, base deficit, hemoglobin, and creatinine, as well as hemodynamic monitoring, such as mean arterial pressure and thermodilution techniques, can become crucial in guiding optimum administration of resuscitation fluids. Mannitol and bicarbonates are available but have limited support in the literature. High-voltage electrical injury patients often develop acute kidney injury requiring dialysis and have increased risks of chronic kidney disease and mortality. Continuous venovenous hemofiltration is a well-supported adjunct to clear the myoglobin load that hemodialysis cannot from circulation.

In forensic practice, determination of electrocution as a cause of death usually depends on the conventional histological examination of electrical mark in the body skin, but the limitation of this method includes subjective bias by different forensic pathologists, especially for identifying suspicious electrical mark. The aim of our work is to introduce Fourier transform infrared (FTIR) spectroscopy in combination with chemometrics as a complementary tool for providing an relatively objective diagnosis. The results of principle component analysis (PCA) showed that there were significant differences of protein structural profile between electrical mark and normal skin in terms of α-helix, antiparallel β-sheet and β-sheet content. Then a partial least square (PLS) model was established based on this spectral dataset and used to discriminate electrical mark from normal skin areas in independent tissue sections as revealed by color-coded digital maps, making the visualization of electrical injury more intuitively. Our pilot study demonstrates the potential of FTIR spectroscopy as a complementary tool for diagnosis of electrical mark., Competing Interests: The authors have declared that no competing interests exist.

Endothelial-to-mesenchymal transition (EndMT) has been implicated in a variety of aberrant wound healing conditions. However, unambiguous evidence of EndMT has been elusive due to limitations of in vitro experimental designs and animal models. In vitro experiments cannot account for the myriad ligands and cells which regulate differentiation, and in vivo tissue injury models may induce lineage-independent endothelial marker expression in mesenchymal cells. By using an inducible Cre model to mark mesenchymal cells (Scx-creERT/tdTomato + ) prior to injury, we demonstrate that musculoskeletal injury induces expression of CD31, VeCadherin, or Tie2 in mesenchymal cells. VeCadherin and Tie2 were expressed in non-endothelial cells (CD31-) present in marrow from uninjured adult mice, thereby limiting the specificity of these markers in inducible models (e.g. VeCadherin- or Tie2-creERT). However, cell transplantation assays confirmed that endothelial cells (ΔVeCadherin/CD31+/CD45-) isolated from uninjured hindlimb muscle tissue undergo in vivo EndMT when transplanted directly into the wound without intervening cell culture using PDGFRα, Osterix (OSX), SOX9, and Aggrecan (ACAN) as mesenchymal markers. These in vivo findings support EndMT in the presence of myriad ligands and cell types, using cell transplantation assays which can be applied for other pathologies implicated in EndMT including tissue fibrosis and atherosclerosis. Additionally, endothelial cell recruitment and trafficking are potential therapeutic targets to prevent EndMT.

Objective: One of the major obstacles in the treatment of severe electrical burns is properly handling the resulting uncontrolled inflammation. Such inflammation often causes secondary injury and necrosis, thus complicating patient outcomes. Vascular endothelial grow factor (VEGF) has emerged as an important mediator for the recruitment of monocytes to the site inflammation. This study was designed to explore the effects and possible mechanism of VEGF on monocyte-endothelial cellular adhesion. To do so, we used a cultured human monocytic cell line (THP-1) that was stimulated with serum derived from rats that had received electrical burns., Methods: Serum was obtained from rats that had received electrical burns. Both the VEGF and soluble flt-1 (sflt-1) concentrations of the serum were determined by double-antibody sandwich ELISA. The concentrations of VEGF, sflt-1, and TNF-α obtained from the cell-free cultured supernatant of THP-1 cells that had been exposed to the serum were then determined by double-antibody sandwich ELISA. Serum-stimulated THP-1 cells were added to wells with a monolayer of endothelial cells to detect the level of monocyte-endothelial cells adhesion. Finally, the state of phosphorylation of AKT was determined by Western blotting., Results: Both in vivo and in vitro studies showed that compared to controls, the levels of VEGF were significantly increased after electrical burns. This increased was accompanied by a reduction of sflt-1 levels. Furthermore, the serum of rats that had received electrical burns was able to both activate monocytes to secrete TNF-α and enhance monocyte-endothelial cell adhesion. Treatment with the serum also resulted in an up-regulation of the phosphorylation of AKT, but had no effect on the total levels of AKT. Phosphatidylinositide 3-kinases (PI3K) inhibition decreased the number of THP-1 cells that were adhered to endothelial cells. Finally, sequestering VEGF with sflt-1 was able to reduce the effect on monocyte-endothelial cells adhesion by blocking the PI3K signaling pathway., Conclusion: Our results indicate that VEGF is implicated in the pathogenesis of inflammation after electrical burns. Inhibition of VEGF activity could attenuate monocyte-endothelial cells adhesion by suppressing the state of phosphorylation of AKT, which is downstream of the PI3K signaling pathway., (Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.)

High-voltage electrical injuries are a devastating form of trauma often treated in burn centers. Examining superficial wounds alone may lead to an inaccurate assessment of local, regional, and systemic severity of injury. In this work, the neurovasculature at sites regionally distinct from the contact wound were assessed for cellular pathology. Nine male Sprague-Dawley rats subjected to 1000 V direct-current shocks were separated into three groups: high-shock (>10-second contact), low-shock (<4-second contact), and control. Injury video was captured with a forward-looking infrared camera, and a thermal excitation analysis was performed. The neurovascular bundles from the iliofemoral region to the distal posterior tibial region were dissected from the hind limbs of the shocked animals and stained by immunohistochemistry for antibodies specific to apoptosis (APO) 1, caspase-3, activating transcription factor 3, high-mobility group box-1, granulocyte-macrophage colony-stimulating factor and interleukin-6. Real-time reverse-transcription polymerase chain reaction was used to quantify differential transcript levels of superoxide dismutases 1, 2, and 3 and heat-shock protein 70 from peripheral blood mononuclear cells and liver tissue. Finally, a protein array was used to identify key inflammatory cytokines in blood plasma. Significant dose-dependent trends were identified in apoptotic markers as well as inflammatory markers in both arterial and nerve tissues. Although arterial tissue exhibited a gradual decline in these markers proximally from the wound site, nerve tissue maintained a constant level at every location. Transcript analysis revealed an up-regulation of extracellular superoxide dismutase, and down-regulation of heat-shock protein 70, whereas plasma inflammatory cytokine levels indicated no significant changes. Thermal excitation analysis revealed a linear temperature increase, with a dose-dependent thermal maximum. In this study the authors have shown that neurovascular APO and inflammation are present at locations extremely proximal to electrical injury contact sites and this appears to be dose-dependent. Nerve tissue APO and inflammation may extend farther proximally than the iliofemoral region, and multiple proapoptotic mechanisms may be activated. No systemic inflammatory response was indicated in this study.

The balance between matrix metalloproteinases and their endogenous tissue inhibitors (TIMPs) is an important component in effective wound healing. The biologic action of these proteins is linked in part to the stoichiometry of TIMP/matrix metalloproteinases/surface protein interactions. We recently described the effect of a glycosylphosphatidylinositol (GPI) anchored version of TIMP-1 on dermal fibroblast biology. Here, cell proliferation assays, in vitro wound healing, electrical wound, and impedance measurements were used to characterize effects of TIMP-1-GPI treatment on primary human epidermal keratinocytes. TIMP-1-GPI stimulated keratinocyte proliferation, as well as mobilization and migration. In parallel, it suppressed the migration and matrix secretion of dermal myofibroblasts, and reduced their secretion of active TGF-β1. Topical application of TIMP-1-GPI in an in vivo excisional wound model increased the rate of wound healing. The agent positively influenced different aspects of wound healing depending on the cell type studied. TIMP-1-GPI counters potential negative effects of overactive myofibroblasts and enhances the mobilization and proliferation of keratinocytes essential for effective wound healing. The application of TIMP-1-GPI represents a novel and practical clinical solution for facilitating healing of difficult wounds., (© 2014 by the Wound Healing Society.)

Objective: To observe the change in expression of vascular endothelial growth factor (VEGF) in serum and wound tissue of rats with electrical burn (EB), and to explore its regulation mechanism in the pathological changes of EB., Methods: Sixty-four SD rats were divided into normal control group (n = 8) and EB group (n = 56) according to the random number table. Eight rats in EB group were sacrificed at post injury hour (PIH) 6 and on post injury day (PID) 1, 3, 7, 14, 21, and 28, to collect wound muscle tissue and serum samples. Histopathological changes in wound tissue were observed with HE staining. The serum content of VEGF was determined with double-antibody sandwich enzyme-linked immunosorbent assay. The expression level of VEGF in wound tissue was determined with Western blotting. VEGF expression intensity in wound tissue was observed with immunohistochemical staining. The microvessel density (MVD) was calculated. The correlation between VEGF expression intensity and MVD was analyzed. Muscle tissue of calf and serum of the rats in normal control group without any treatment were collected for above-mentioned observations and determinations. Data were processed with one-way analysis of variance and Spearman hierarchy correlation analysis, and LSD-t test was applied for paired comparison., Results: (1) In EB group, breakage of muscle fiber, heavy infiltration of inflammatory cells, and obvious tissue edema were observed at PIH 6 and on PID 1; new vessels were observed on PID 3; amount of granulation tissue and number of new vessels were found to be increased on PID 7. (2) In EB group, the serum level of VEGF was (43 ± 11) pg/mL at PIH 6, (44 ± 11) pg/mL on PID 1, and (74 ± 27) pg/mL on PID 14, which were all significantly higher than that in normal control group [(15 ± 9) pg/mL, with t values from 4.001 to 5.724, P values all below 0.01]. (3) The protein expression level of VEGF of wound tissue in EB group was higher than that in normal control group (0.21 ± 0.09) at each time point. The protein expression level of VEGF in EB group peaked on PID 7 (0.63 ± 0.13, t = 4.965, P < 0.05). (4) In EB group, strongly positive expression of VEGF was observed in inflammatory cells at early stage and in new vascular endothelial cells at late stage. (5) The expression intensity of VEGF was positively correlated with MVD in wound tissue on PID 3, 7, 14, 21, and 28 in EB group (r(s) = 0.834, P < 0.01)., Conclusions: Different expression levels of VEGF were observed in serum and wound tissue of rats at various stages after EB, and they were closely correlated with different stages of fluid exudation and wound healing process after EB.

Electrical injuries are devastating and are difficult to manage due to the complexity of the tissue damage and physiological impacts. A paucity of literature exists which describes models for electrical injury. To date, those models have been used primarily to demonstrate thermal and morphological effects at the points of contact. Creating a more representative model for human injury and further elucidating the physics and pathophysiology of this unique form of tissue injury could be helpful in designing stage-appropriate therapy and improving limb salvage. An electrical burn delivery system was developed to accurately and reliably deliver electrical current at varying exposure times. A series of Sprague-Dawley rats were anesthetized and subjected to injury with 1000 V of direct current at incremental exposure times (2-20 seconds). Whole blood and plasma were obtained immediately before shock, immediately postinjury, and then hourly for 3 hours. Laser Doppler images of tissue adjacent to the entrance and exit wounds were obtained at the outlined time points to provide information on tissue perfusion. The electrical exposure was nonlethal in all animals. The size and the depth of contact injury increased in proportion to the exposure times and were reproducible. Skin adjacent to injury (both entrance and exit sites) exhibited marked edema within 30 minutes. In adjacent skin of upper extremity wounds, mean perfusion units increased immediately postinjury and then gradually decreased in proportion to the severity of the injuries. In the lower extremity, this phenomenon was only observed for short contact times, while longer contact times had marked malperfusion throughout. In the plasma, interleukin-10 and vascular endothelial growth factor levels were found to be augmented by injury. Systemic transcriptome analysis revealed promising information about signal networks involved in dermatological, connective tissue, and neurological pathophysiological processes. A reliable and reproducible in vivo model has been developed for characterizing the pathophysiology of high-tension electrical injury. Changes in perfusion were observed near and between entrance and exit wounds that appear consistent with injury severity. Further studies are underway to correlate differential mRNA expression with injury severity.

Background: Electrical injuries induce progressive tissue loss caused by free oxygen radicals released from neutrophil aggregates. Fucoidin, a potent inhibitor of L-selectin function, reduces the aggregation of neutrophils. The aim of this study was to evaluate the effect of fucoidin on tissue damage in rat electrical burn injury model., Methods: Forty-two male Wistar albino rats (250-300 g) were divided into 3 groups (Group A (n=6), control group without electrical burn injury; Groups B (n=18) and C (n=18), electrical burn injury groups without and with fucoidin therapy, respectively). Three separate analyses were performed at different time points on 6 out of 18 mice from Group B and C at each time point. Biochemistry (myeloperoxidase and malondialdehyde levels) and histopathology (number of neutrophils) of the skin and muscle biopsies at 1st hour; tissue edema (ratio of wet weight/dry weight of extremities) at 24th hour; and necrotic areas at 7th day after electrical injury were evaluated. The electrical burn was induced by exposing rats to 220 V AC between their left upper extremity and right lower extremity for 10 s. Fucoidin was administered as 25 mg/kg intravenous bolus injection at 15 min after electrical burn injury., Results: Myeloperoxidase and malondialdehyde levels, number of neutrophils, tissue edema, and necrotic area were significantly less in fucoidin-applied rats than the group without fucoidin therapy., Conclusions: Fucoidin inhibits tissue damage induced by electrical burn injury in rats by reducing necrotic area, edema and number of neutrophils., (Copyright © 2011 Elsevier Ltd and ISBI. All rights reserved.)

The electrophysiological and morphological changes of nerve fibers induced by electrical injury have been widely addressed. However, the changes of ion channels in neurons after electrical shocks have not been systematically investigated yet. In this study, the sciatic nerves of rabbit were injured by 50 V 50 Hz, 110 V 50 Hz, and 220 V 50 Hz alternating current, respectively. One week later, the expression levels and electrophysiological changes of voltage-gated potassium (Kv) and sodium (Nav) channels in dorsal root ganglia (DRG) neurons were evaluated by RT-PCR, immunofluorescence staining and patch clamp technique. The Nav1.1 expression was decreased by 50V injury. The Kv1.2, Kv1.4, Nav1.1 and Nav1.7 expression levels and Kv current densities were reduced after 110 V injury. Under the 220 V injury circumstance, Kv1.2, Nav1.1, Nav1.7 expression levels, Kv current densities and TTX-R Na(+) current densities were significantly decreased, while TTX-S Na(+) current densities increased. These findings suggest that the expression levels, subunit compositions, and electrophysiological properties of Kv and Nav channels are altered after electrical injury, and the severity of injury gets worse as injury voltage increases., (Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.)

Effects of imposed large supraphysiological transmembrane potential (TP) pulses on channel proteins, particularly on the voltage-gated Na channels, were investigated. Voltage clamp techniques were used to deliver both shock and stimulation pulses, and to monitor changes in the channel functions. Our experimental results indicated that more than one 4 ms duration TP shock of -450 mV resulted in electroconformational denature of voltage-gated Na channels. This resulted in functional reductions in muscle cells' excitability. We quantified the TP shock-induced decrease in the Na channel currents, compared the pre- and post-shocked Na channel currents' voltage dependency, and studied the reversibility of the electroconformationally denatured ion channel proteins. These observations are particularly relevant to the problem of explaining the neuromuscular damage following high voltage electrical shock injuries despite no evidence of a thermal injury component.

Despite decades of research, our understanding of human hypertrophic scar is limited. A reliable animal model could significantly increase our understanding. We previously confirmed similarities between scarring in the female, red, Duroc pig and human hypertrophic scarring. The purpose of this study was to: (1) measure vascular endothelial growth factor (VEGF) and nitric oxide (NO) levels in wounds on the female Duroc; and (2) to compare the NO levels to those reported for human hypertrophic scar. Shallow and deep wounds were created on four female Durocs. VEGF levels were measured using ELISA and NO levels with the Griess reagent. VEGF and NO levels were increased in deep wounds at 10 days when compared to shallow wounds (p < 0.05). At 15 weeks, VEGF and NO levels had returned to the level of shallow wounds. At 21 weeks, VEGF and NO levels had declined below baseline levels in deep wounds and the NO levels were significantly lower (p < 0.01). We found that VEGF and NO exhibit two distinctly different temporal patterns in shallow and deep wounds on the female Durocs. Furthermore, NO is decreased in female, Duroc scar as it is in human, hypertrophic scar further validating the usefulness of the model.

The Akt serine/threonine kinase mediates pro-survival signalings in retina and was reported to be activated in a response to some retinal and optic nerve injuries. Human and experimental glaucoma induce apoptosis of retinal ganglion cells (RGCs). The purpose of this study is to test whether episcleral vein cauterization (EVC) to chronically elevate intraocular pressures (IOPs) in rats increase apoptosis of RGCs and affect activation of Akt and its upstream insulin-like growth factor (IGF)-1 receptor/Insulin receptor. Three episcleral veins in left eyes of Sprague-Dawley rats were cauterized to elevate IOPs. Up to 6 months, IOPs were monitored and the retina was dissected at several time points. The numbers of terminal dUTP nick end labeling (TUNEL)-positive cells and those of RGCs labeled with fluorogold were counted in flat-mounted retina. Immunohistochemistry and immunoblotting were performed to identify cells expressing phosphorylated Akt and to quantify the phospho- to total ratios of Akt and IGF-1 receptor/insulin receptor. EVC significantly elevated IOPs up to 2 months, increased TUNEL-positive cells in an IOP-dependent fashion, and reduced 34.5% of RGCs at 6 months (P<0.001) compared with contralateral retinas. Phosphorylated Akt was specifically expressed in RGCs until 1 month after cauterization. Akt (P=0.036) and IGF-1 receptor/Insulin receptor (P=0.003) were transiently phosphorylated at 3 days. Intrinsic activation of the IGF-1 receptor/Insulin receptor to Akt pathway may occur in RGCs in retina with EVC.

Objective: To evaluate the mechanisms of thrombosis in the early stage of electrical injury., Methods: Endothelin-1(ET-1), prostacylin(PGI2), platelet alpha-granule membrane protein (Gmp-140), thromboxane (TXB2), and plasminogen(PLG-A) were measured in 26 patients with electrical injury., Results: It was found that GMP-140 and ET-1 increased significantly(P < 0.01), PLG-A showed a significant change 2 weeks after the injury, while there was an imbalance between TXB2 and PGI2., Conclusion: It is believed that change in one or several mediators mentioned above may trigger thrombosis after electrical injury.

The purpose of the present study was to analyse the course of patients hospitalised with electrical burn wounds in the past 25 years at a major children's hospital in the United States in order to devise safe and cost effective management strategies for these patients. The study was a retrospective chart review of patients with electrical injuries admitted to the hospital between 1971 and 1995. We identified 127 children who were included in the study. Injuries resulted from biting an electrical cord (oral injury) (n = 48), placing an object into an electrical socket (outlet injury) (n = 33), contacting a low voltage wire or appliance indoors (low voltage household injury) (n = 25), contacting a high voltage wire outdoors (high voltage wire injury) (n = 18), or being struck by lightning (n = 3). A retrospective review revealed that the great majority of patients with low voltage electrical injuries did not need admission to the hospital and could have been cared for on an outpatient basis. Almost every patient with high voltage injury had a justified admission due to the severity of the injury. On the basis of these results we conclude that we can safely reduce the number of admissions to the hospital for children with low voltage minor electrical injuries.

The authors report the study of the kinetics in serum and urine and the clinical safety of a high dose of teicoplanin administered in a 19 year-old patient with major burns (60% of body surface area, the half of which consisting of third-degree burns and UBS at 150) and S aureus meticillin-resistant infection. At day 1, he was given two loading infusions of 12 mg.kg-1 teicoplanin followed by 12 mg.kg-1 per day of treatment. At all times, Cmin concentrations were below the limit value of 8 mg.mL-1. Therefore the therapeutic regimen was increased on several occasions. On days 5, 8 and 15, Cmin were measured by FPIA. Pharmacokinetic analysis was performed at day 16, (i.e., 20 mg.kg-1) and urine was also collected over at least 12 hours. At day 16, serum and urine samples were assayed by HPLC. Data were analyzed with a noncompartmental method. The duration of treatment was 20 days and no adverse events were noted. Bacteriological tests performed at the end of treatment demonstrated the elimination of the agent responsible over the infection. While pharmacokinetics were not assessed at plateau, Cmin remained very low. Vss was similar to values obtained in healthy subjects while total clearance was increased. This phenomenon was explained by the increase of total clearance and a nonrenal translesional diffusion suggested by the body surface area affected by third-degree burns. Finally, the cost of increasing doses of teicoplanin must be taken in account.

A 32-year-old male was referred to intensive care with possible respiratory sepsis 15 days after sustaining 73 per cent TBSA electrical burns. Investigation revealed previously undiagnosed hyperosmolar non-ketotic diabetic coma. The aetiology, pathogenesis and management of this recognized complication of major burns is discussed. An interesting feature of this case is recovery from 73 per cent burns, severe hyperosmolar non-ketotic diabetic coma and a serum osmolality of 429 mosmol/kg, each of which carry a high mortality probability.

Electrical burns or ischemia (induced by vascular ligation) were produced in the legs of 15 anesthetized dogs to study evolution of tissue changes compared with impedance alterations. After the application of 1-ampere currents at 60 Hz, animals were monitored from 1 to 4 days. Muscle impendance was measured with frequency sweeping to determine tissue destruction. Nuclear magnetic resonance spectroscopy (phosphorus 31) was used to assess metabolic activity, and results were compared to impedance measurements. In burned limbs, 70% reduction in muscle impedance was seen, which corresponds to decreased metabolic activity (absent organic phosphates) and suggests necrosis. Visually viable tissue had impedance decreases of 25% and levels of organic phosphates slightly lower than normal. Relaxation frequencies in dogs with severe burns exceeded 80 kHz; in viable tissue, 30 to 40 kHz (normal: 30 kHz). In ischemic muscle, organic phosphates decreased rapidly (1 to 2 hours); impedance changes evolved more slowly (1 day), but they ultimately reached the same degree of severity. Measurement of impedance may be a valuable adjunct in the evaluation of electrical burns, since significant changes strongly suggest nonviability.

The aim of this study was to test the potential of liposomes as drug carriers to the ulcerated oral mucosa. Radioactive triamcinolone acetonide palmitate (3H-TRMAp) was encapsulated in large multilamellar lipid vesicles and served as the test lotion. 3H-TRMAp in solution served as control. Forty-six hamsters were divided into three groups. In group I, multiple confluent ulcers in both cheek pouches were treated by topical application. In group II, single ulcers on the cheeks were treated by intramucosal injection. In group III, multiple confluent ulcers were produced in the cheek pouch on one side, with a single ulcer in the contralateral cheek pouch; no drug was applied, and the tissues were prepared for histology. Hamsters were killed at three and 24 hours, respectively, after treatment. Pouches were divided into ulcerated and intact adjacent mucosa. Cheeks were divided into ulcerated mucosa and distant mucosa. Drug levels in the four mucosal portions as well as in the blood, liver, spleen, brain, and thalamic region were determined by radioactive tracer technique. At three hours, liposomal drug concentrations were lower than in control animals in the brain and the thalamic region. At 24 hours, liposomal drug values were higher than in control animals in the ulcerated mucosa and lower than in control animals in the thalamic region. Mean drug concentrations in the ulcerated mucosa were higher in group II than group I. The results parallel those of Mezei and Gulasekharam (1980, 1982); liposomes increase local and decrease systemic drug concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Deposition of calcium salts on collagen fibres has been shown to occur in cathode areas from 2 days to 2 months after exposure to direct current (d.c.) via contact knobs measuring 12 mm in diameter using energy level from 0.5 to 96 J and on day 7 after exposure to alternating current (a.c.) via pointed electrodes using energy level from 30 to 50 J. In order to determine the statistical relation of this histological observation to the type of energy applied 1095 biopsies from 49 pigs including biopsies from skin areas exposed to heat, 50 Hz a.c., 100 kHz a.c. and d.c. as well as from unexposed skin were examined. The specificity was 1.0 using calcium deposition as the test criterium. The sensitivity for cathode areas was found to vary from 0.52 to 1.0 depending on the biopsy technique and the number of days after exposure. Calcium salts on collagen fibres seem uniformly to be present in the cathode area from day 4 to 7, the positive test answer being depending on the biopsy technique. For 50 Hz a.c. the sensitivity using a pointed electrode was found to vary from 0.08 to 0.27 dependent on the number of days after exposure. For all other types of energy the sensitivity was 0.

A reproducible electrical injury to the hind limb was produced in rats, an injury characterized by progressive tissue necrosis. Serial histochemical examinations of cross sections with a peroxidase-antiperoxidase method revealed increased production of arachidonic acid metabolites, especially thromboxane, at distal sites near the entrance wound and in periosseous tissues more proximally. Levels of these vasoactive substances remained elevated during the time of progressive necrosis and demarcation of seemingly normal, uninjured tissue. Treatment with agents capable of blocking thromboxane production allowed tissue salvage, as evidenced by a decreased autoamputation rate and an increased total surviving length. From this study it appears that an electrical injury is thermal trauma, producing elevated levels of arachidonic acid metabolites in areas of greatest heat production. Prolonged thromboxane excess, with resultant vasoconstriction and thrombosis in the microcirculation, is seen to play a key role in the progressive tissue loss characteristic of the injury. The use of antithromboxane agents may be of benefit in halting this progression and salvaging tissue in these devastating injuries.