Melatonin attenuates oxidative stress and modulates inflammatory response after experimental burn trauma

Introduction. Thermal injury activates an inflammatory response. Melatonin possesses anti-oxidant and anti-inflammatory properties. The objective of the present work was to study melatonin effects on the inflammatory response under conditions of oxidative stress during the early stage of thermal injury. Materials and methods. We used 24 white male rats of Wistar breed, randomly divided into three experimental groups. Group one was the control, group two was inflicted with burn trauma, and group three was inflicted with burn trauma, with melatonin application following the thermal injury. Melatonin was applied twice in doses of 10 g/kg b.m. immediately after the burn trauma and again at 12 hours. Plasma levels of tumor necrosis-factor-α (TNF-α), a pro-inflammatory mediator, and of interleukin-10 (Il-10), an anti-inflammatory mediator, were examined and their ratio was calculated. The levels of malondialdehyde (MDA), an oxidative stress marker, were also estimated. Results. Thermal trauma significantly increased plasma TNF-α levels (ð\u3c0.01) and TNF-α /IL-10 ratio but did not change IL-10 ones. Plasma MDA concentrations were significantly elevated as well (ð\u3c0.0001). Melatonin application significantly reduced TNF-α (ð\u3c0.05), increased IL-10 (ð\u3c0.05), down-regulated TNF-α/IL-10 ratio and changed MDA concentrations (ð\u3c0.01). In conclusion, our results show that local alteration induces oxidative stress and inflammatory response with TNF-α /IL-10 disbalance. Melatonin modulates this response and attenuates oxidative stress in experimental burn injury

An empirical analysis of potential cyclist injuries and cycling outfit comfort

This study investigated the relationship between pain/injury and training characteristics in cyclists. In addition, ergonomic wear comfort of their garments was investigated. A total of 94 complete questionnaire responses were analyzed. The result indicated that lower back pain was the most prevalent injury causing the highest rates of functional damage and medical attention. The injury level of cyclists was affected by the cluster with elite cyclists reporting pain while cycling. Many cyclists were not very satisfied with the comfort level of their current outfit, 39% of respondents were experienced with different discomfort sensations. The most frequent causes of discomfort were thermal and moisture discomfort sensation related to fabric characteristics. Moreover, design and fit of the garment were considered as cause of discomfort next to thermal discomfort sensation. Therefore, it could be concluded that garments that have good ventilation or breathability and very good fit values were preferred by cyclists. Design, limited choice (availability), appearance/look and quality were the main reason for their brand selection preferences

Prevalence and Patterns of Injury-Related Mortality in Nevada

Too many lives are lost to injury in the United States and in Nevada. Nearly 200,000 people in our country die each year from injuries, which is equivalent to one death every three minutes (CDC 2017b). Each of these deaths not only extinguishes a life, but also affects the friends, family, and community of the deceased. And deaths from injury are costly: researchers estimate that costs from fatal injuries exceed $200 billion (CDC 2017b). Injury refers to damage to the body from some external force, such as from a car crash or a fall, including kinetic, chemical, electrical, thermal or other forces. There are multiple types of death from injury. Health researchers and policymakers classify injuries as unintentional or intentional, and if intentional, injury deaths are further classified as either suicide or homicide. Researchers and policymakers further categorize injuries by the mechanism or circumstances of the injury (such as motor vehicle crash, poisoning, or firearm)

The effect of environment on post surgical overall well-being and pain sensitivity in an animal model

With chronic post surgical pain affecting up to one third of patients undergoing surgeries and the price of treatment being astoundingly high there has been a transition in research to investigate and identify risk factors. Through identification of risk factors new preventative measures can be taken to ensure better surgical outcomes. The role that psychosocial factors can play in the development of chronic post surgical pain has long been recognized yet its mechanisms are still unknown. We aim to investigate how environment can play a direct role in pain perception and sensitivity. We used a Chronic Mild Stress (CMS) paradigm to induce depression in 10 adult male mice, we used 10 control mice who were left in standard opti cages, and 10 enriched mice who were placed in large enrichment cages. CMS mice were exposed to a series of stressors and all mice underwent spared nerve injury surgery. During spared nerve injury the common peroneal and tibial branches of the sciatic nerve were severed while the sural branch was left intact. Overall well-being and pain threshold of mice were tested via Von Frey, Hot Plate, Heat Place Preference, Dynamic Weight Bearing, Hole Board, and Social Interaction. It was found that CMS mice experienced thermal hyperalgesia yet normal thermal threshold sensation. CMS mice also spent less time interacting with novel mice in social interaction, and less amount of time exploring the center of the hole board arena than control or enriched mice. While Von Frey results did not change over the course of the experiment, dynamic weight bearing results indicated spared nerve injury surgery was successful and produced chronic pain. Results indicate that environment plays a role in thermal pain perception and CMS affected overall well being of mice as CMS mice exhibited more timid and anxious behavior

Enhanced Platelet-activating Factor synthesis facilitates acute and delayed effects of ethanol intoxicated thermal burn injury

Thermal burn injuries in patients alcohol intoxicated result in greater morbidity and mortality. Murine models combining ethanol and localized thermal burn injury reproduce the systemic toxicity seen in human subjects, which consists of both acute systemic cytokine production with multiple organ dysfunction, as well as a delayed systemic immunosuppression. However, the exact mechanisms for these acute and delayed effects are unclear. These studies sought to define the role of the lipid mediator Platelet-activating factor (PAF) in the acute and delayed effects of intoxicated burn injury. Combining ethanol and thermal burn injury resulted in increased enzymatic PAF generation in a keratinocyte cell line in vitro, human skin explants ex vivo, as well as in murine skin in vivo. Further, the acute increase in inflammatory cytokines such as IL-6, and the systemic immunosuppressive effects of intoxicated thermal burn injury, were suppressed in mice lacking PAF receptors. Together, these studies provide a potential mechanism and novel treatment strategies for the augmented toxicity and immunosuppressive effects of thermal burn injury in the setting of acute ethanol exposure, which involves the pleotropic lipid mediator PAF

Spared nerve injury rats exhibit thermal hyperalgesia on an automated operant dynamic thermal escape Task

Well-established methods are available to measure thermal and mechanical sensitivity in awake behaving rats. However, they require experimenter manipulations and tend to emphasize reflexive behaviors. Here we introduce a new behavioral test, with which we examine thermal sensitivity of rats with neuropathic injury. We contrast thermal hyperalgesia between spared nerve injury and chronic constriction injury rats. This device is a fully automated thermal sensitivity assessment tool designed to emphasize integrated learned responses to thermal painful and non-painful stimuli that are applied dynamically to a surface on which the animal is standing. It documents escape behavior in awake, unrestrained animals to innocuous and noxious heating of the floor where the animal is located. Animals learn to minimize pain by escaping to the opposite non-heated side; escape latency is recorded. On this device, thermal stimulus-response curves showed > 6°C leftward shift in both groups of neuropathic rats. In contrast, when these animals were tested on hotplate the stimulus-response shift was < 2°C. Spared nerve injury rats showed even less evidence for thermal hyperalgesia when thermal sensitivity was tested by measuring paw withdrawal to infrared heating, plantar test. The implications of test dependent magnitude of thermal hyperalgesia are discussed from the viewpoint of the tests used, as well as the animal models studied. It is argued that the dynamic thermal operant task reveals the relevance of the neuropathic injury associated pain-like behavior in relation to the whole organism

Cooling or Warming the Esophagus to Reduce Esophageal Injury During Left Atrial Ablation in the Treatment of Atrial Fibrillation.

Ablation of the left atrium using either radiofrequency (RF) or cryothermal energy is an effective treatment for atrial fibrillation (AF) and is the most frequent type of cardiac ablation procedure performed. Although generally safe, collateral injury to surrounding structures, particularly the esophagus, remains a concern. Cooling or warming the esophagus to counteract the heat from RF ablation, or the cold from cryoablation, is a method that is used to reduce thermal esophageal injury, and there are increasing data to support this approach. This protocol describes the use of a commercially available esophageal temperature management device to cool or warm the esophagus to reduce esophageal injury during left atrial ablation. The temperature management device is powered by standard water-blanket heat exchangers, and is shaped like a standard orogastric tube placed for gastric suctioning and decompression. Water circulates through the device in a closed-loop circuit, transferring heat across the silicone walls of the device, through the esophageal wall. Placement of the device is analogous to the placement of a typical orogastric tube, and temperature is adjusted via the external heat-exchanger console

Heightened Levels of Microvesicle Particles Resulting from Combination of Ethanol and Thermal Burn Injury

Ethanol (EtOH), in combination with thermal burn injury, is a clinically significant problem resulting in an increase in morbidity and mortality due to acute multi-organ toxicity from excess systemic cytokine release. This intoxicated thermal burn affects close to 50% of the total numbers of hospital-admitted burn patients and currently has no standard treatment. However, using in vitro cellular and in vivo murine models, our group has provided data implicating the augmented production of the lipid mediator Platelet-activating factor (PAF) in keratinocytes in response to intoxicated thermal burn injury in the subsequent pathology. Of importance, our group has demonstrated that activation of the keratinocyte PAF-receptor (PAFR) results in the generation of subcellular microvesicle particles (MVP) which carry, and thus, serve to protect this labile lipid mediator PAF. The goal of the current studies is to define the exact mechanisms by which EtOH + burn injury generates augmented PAF production, and the role of MVP in this process. Using the human keratinocyte derived cell line HaCaT, we demonstrate that EtOH alone can generate MVP at EtOH dosages of 1% or more over 4 hours and synergizes with thermal burn injury. Use of PAFR-positive and PAFR-negative epithelial cell lines as well as siRNA knock-down approaches of the PAFR in HaCaT cells in conjunction with EtOH + burn studies, all indicate that burn injury-induced MVP release is PAFR-dependent. Moreover, studies using wild-type and PAFR-KO mice demonstrate increased numbers of MVP in the skin and in plasma following intoxicated burn injury in a PAFR-dependent manner. Studies with HaCaT cells revealed that the MVP contain large amounts of PAFR agonistic activity. Our final study in HaCaT cells revealed that the cytosolic phospholipase A2 (cPLA2) inhibitor pyrrophenone, which blocks enzymatic PAF synthesis, also attenuates the exaggerated MVP formation in response to EtOH + thermal burn injury. These studies fit with a novel model whereby EtOH + thermal burn injury generates increased PAF via cPLA2 activation through the lipid mediated Platelet-activating factor pathway, which then generates high levels of PAF-laden MVP which are in part responsible for the subsequent pathology of intoxicated thermal burn injury

Independent Risk Factors for Injury in Pre-School Children: Three Population-Based Nested Case-Control Studies Using Routine Primary Care Data

Background: Injuries in childhood are largely preventable yet an estimated 2,400 children die every day because of injury and violence. Despite this, the factors that contribute to injury occurrence have not been quantified at the population scale using primary care data. We used The Health Improvement Network (THIN) database to identify risk factors for thermal injury, fractures and poisoning in pre-school children in order to inform the optimal delivery of preventative strategies. Methods: We used a matched, nested case-control study design. Cases were children under 5 with a first medically recorded injury, comprising 3,649 thermal injury cases, 4,050 fracture cases and 2,193 poisoning cases, matched on general practice to 94,620 control children. Results: Younger maternal age and higher birth order increased the odds of all injuries. Children’s age of highest injury risk varied by injury type; compared with children under 1 year, thermal injuries were highest in those age 1-2 (OR = 2.43, 95%CI 2.23–2.65), poisonings in those age 2-3 (OR = 7.32, 95%CI 6.26–8.58) and fractures in those age 3-5 (OR = 3.80, 95%CI 3.42–4.23). Increasing deprivation was an important modifiable risk factor for poisonings and thermal injuries (tests for trend p#0.001) as were hazardous/harmful alcohol consumption by a household adult (OR = 1.73, 95%CI 1.26–2.38 and OR = 1.39, 95%CI 1.07–1.81 respectively) and maternal diagnosis of depression (OR = 1.45, 95%CI 1.24–1.70 and OR = 1.16, 95%CI 1.02–1.32 respectively). Fracture was not associated with these factors, however, not living in single-adult household reduced the odds of fracture (OR = 0.88, 95%CI 0.82–0.95). Conclusions: Maternal depression, hazardous/harmful adult alcohol consumption and socioeconomic deprivation represent important modifiable risk factors for thermal injury and poisoning but not fractures in preschool children. Since these risk factors can be ascertained from routine primary care records, pre-school children’s frequent visits to primary care present an opportunity to reduce injury risk by implementing effective preventative interventions from existing national guidelines