Nonlethal Injury Research Articles

Clinical and experimental evidence for differences between cardiac troponin I and T in acute and chronic cardiovascular conditions

Abstract Background Clinical and scientific practice operate under the assumption that systemic levels of cardiac troponin I (cTnI) and troponin T (cTnT) are indicative of the same underlying pathophysiological mechanisms and can be utilized interchangeably. Purpose To assess cTnI and cTnT levels and their ratio for differences in various cardiovascular conditions. Methods Individuals from three prospective clinical studies with a centrally adjudicated diagnosis were categorized into three groups: no known cardiac disease, chronic cardiac disease, and acute cardiac disease. Circulating cTnI and cTnT concentrations were measured using high-sensitivity assays (hs-cTnI-Architect, hs-cTnT-Elecsys) and the cTnI/cTnT ratio was calculated. Findings were validated using a second hs-cTnI assay (hs-cTnI-Clarity) and externally validated in independent cohorts. The cTnI/cTnT ratio was also assessed in five different non-lethal and lethal experimental models of cardiomyocyte injury. Results Of the 9704 included individuals, 9% had no known cardiac disease, 69% chronic cardiac disease, and 22% acute cardiac disease. No known cardiac disease and chronic cardiac disease were associated with a disproportional increase in cTnT compared to cTnI (cTnI/cTnT ratio, median 0.50, IQR 0.38-0.69 and 0.53, IQR 0.37-0.80). In contrast, cTnI concentrations were increased compared to cTnT in patients with acute cardiac disease, resulting in a cTnI/cTnT ratio of 1.62 (IQR 0.77-4.31). Findings were consistent using an alternative cTnI assay and in external validation cohorts (n=2776) where the cTnI/cTnT ratio was lower in those without cardiac disease (0.33 (IQR 0.25-0.50), 0.64 (IQR 0.40-1.05)) and with chronic cardiac disease (0.50 (IQR 0.32-0.75), 0.60 (IQR 0.38-1.00)), compared to those with acute cardiac disease (2.22 (IQR 1.08-5.27), 2.28 (IQR 1.01-5.67)). Non-lethal cardiomyocyte injury models showed a predominant release of cTnT with cTnI/cTnT ratios <0.5, and lethal injury models a predominant release of cTnI with cTnI/cTnT ratios >1. Conclusion Differences in cTnI and cTnT levels were observed in individuals with chronic and acute cardiac conditions, leading to distinct cTnI/cTnT ratios in both clinical and experimental settings. As a result, the interchangeability of cTnI and cTnT in present-day clinical and scientific settings needs to be reevaluated.Central illustration

Past energy allocation overwhelms current energy stresses in determining energy allocation trade-offs.

Regeneration of lost appendages is a gradual process in many species, spreading energetic costs of regeneration through time. Energy allocated to the regeneration of lost appendages cannot be used for other purposes and, therefore, commonly elicits energetic trade-offs in biological processes. We used limb loss in the Asian shore crab Hemigrapsus sanguineus to compare the strength of energetic trade-offs resulting from historic limb losses that have been partially regenerated versus current injuries that have not yet been repaired. Consistent with previous studies, we show that limb loss and regeneration results in trade-offs that reduce reproduction, energy storage, and growth. As may be expected, we show that trade-offs in these metrics from historic limb losses far outweigh trade-offs from current limb losses, and correlate directly with the degree of historic limb loss that has been regenerated. As regenerating limbs get closer to their normal size, these historical injuries get harder to detect, despite the continued allocation of additional resources to limb development. Our results demonstrate the importance of and a method for identifying historic appendage losses and of quantifying the amount of regeneration that has already occurred, as opposed to assessing only current injury, to accurately assess the strength of energetic trade-offs in animals recovering from nonlethal injury.

Latitudinal and temporal variation in injury and its impacts in the invasive Asian shore crab Hemigrapsus sanguineus

Nonlethal injury is a pervasive stress on individual animals that can affect large portions of a population at any given time. Yet most studies examine snapshots of injury at a single place and time, making the implicit assumption that the impacts of nonlethal injury are constant. We sampled Asian shore crabs Hemigrapsus sanguineus throughout their invasive North American range and from the spring through fall of 2020. We then documented the prevalence of limb loss over this space and time. We further examined the impacts of limb loss and limb regeneration on food consumption, growth, reproduction, and energy storage. We show that injury differed substantially across sites and was most common towards the southern part of their invaded range on the East Coast of North America. Injury also varied idiosyncratically across sites and through time. It also had strong impacts on individuals via reduced growth and reproduction, despite increased food consumption in injured crabs. Given the high prevalence of nonlethal injury in this species, these negative impacts of injury on individual animals likely scale up to influence population level processes (e.g., population growth), and may be one factor acting against the widespread success of this invader.

A non-human primate model of acute liver failure suitable for testing liver support systems.

Acute hepatic failure is associated with high morbidity and mortality for which the only definitive therapy is liver transplantation. Some fraction of those who undergo emergency transplantation have been shown to recover native liver function when transplanted with an auxiliary hepatic graft that leaves part of the native liver intact. Thus, transplantation could have been averted with the development and use of some form of hepatic support. The costs of developing and testing liver support systems could be dramatically reduced by the availability of a reliable large animal model of hepatic failure with a large therapeutic window that allows the assessment of efficacy and timing of intervention. Non-lethal forms of hepatic injury were examined in combination with liver-directed radiation in non-human primates (NHPs) to develop a model of acute hepatic failure that mimics the human condition. Porcine hepatocyte transplantation was then tested as a potential therapy for acute hepatic failure. After liver-directed radiation therapy, delivery of a non-lethal hepatic ischemia-reperfusion injury reliably and rapidly generated liver failure providing conditions that can enable pre-clinical testing of liver support or replacement therapies. Unfortunately, in preliminary studies, low hepatocyte engraftment and over-immune suppression interfered with the ability to assess the efficacy of transplanted porcine hepatocytes in the model. A model of acute liver failure in NHPs was created that recapitulates the pathophysiology and pathology of the clinical condition, does so with reasonably predictable kinetics, and results in 100% mortality. The model allowed preliminary testing of xenogeneic hepatocyte transplantation as a potential therapy.

Differential Response of Leafminer Flies Liriomyza trifolii (Burgess) and Liriomyza sativae (Blanchard) to Rapid Cold Hardening.

Simple SummaryLiriomyza trifolii (Burgess) and L. sativae (Blanchard) are closely-related, polyphagous leafminers that occur worldwide and presumably compete with each other. In this study, we evaluated the response of pupae and adults from both species to acute (2 h) cold exposures. The results were used to identify the lethal temperature for 80% of the population (LT80) for each species. In a separate set of experiments, insects were cooled to one of six nonlethal temperatures (0–5 °C) for 4 h and then cooled to the LT80 for 2 h to evaluate their rapid cold hardening (RCH) response. L. trifolii exhibited stronger cold tolerance than L. sativae; furthermore, the supercooling point of L. trifolii was significantly lower than that of L. sativae. RCH was induced in pupae of both species at a range of low temperatures (0–5 °C), and L. sativae pupae showed a more robust RCH response (e.g., lower supercooling pointand more durable RCH) than L. trifolii pupae. Our results indicate that subtle differences in RCH and basal cold tolerance impact the competitiveness of the two leafminers.Rapid cold hardening (RCH) is a rapid and critical adaption of insects to sudden temperature changes but is often overlooked or underestimated as a component of survival. Thus, interspecific comparisons of RCH are needed to predict how phenotypes will adapt to temperature variability. RCH not only enhances cold survival but also protects against non-lethal cold injury by preserving essential functions such as locomotion, reproduction, and energy balance. This study investigated the difference in basal cold tolerance and RCH capacity of L. trifolii and L. sativae. In both species, the cold tolerance of pupae was significantly enhanced after short-term exposure to moderately cold temperatures. The effect of RCH last for 4 h in L. sativae but only 2 h in L. trifolii. Interestingly, L. trifolii adults had a RCH response but L. sativae adults failed to acclimate. Short-term acclimation also lowered the supercooling point significantly in the pupae of both species. Based on these results, we propose a hypothesis that these differences will eventually affect their competition in the context of climate change. This study also provides the basis for future metabolomic and transcriptomic studies that may ultimately uncover the underlying mechanisms of RCH and interspecific competition between L. trifolii and L. sativae.

Characteristics of bodily injuries of the pelvic girdle and lower extremities in car trauma

Background. Fractures of the pelvic girdle and lower extremities as a result of a road traffic accident are the most frequent localization of injuries in victims, however, the structure of pedestrian and intra-salon injuries has not been sufficiently studied. Objective - to study the nature of injuries in victims of a car injury to the pelvic girdle and lower extremities. Methods. Research material - 170 acts of primary forensic medical examinations of victims with fractures of the pelvic bones and long bones of the lower extremities, received as a result of a non-lethal automobile injury. An expert assessment of the nature of bodily injuries was carried out at the Kharkiv Regional Bureau of Forensic Medicine (KRBSFM) within a period of no more than 1 month after injury. Acts of primary forensic medical examinations were selected at random for the period February - June 2018. Research methods - retrospective analysis, descriptive statistics. Results. Among the injured as a result of a car injury - 129 (75.9%) pedestrians, 23 (13.5%) drivers, 14 (8.2%) front seat passengers and 4 (2.4%) rear seat passengers. Thus, pedestrians and car drivers are the most vulnerable to road traffic injuries; the most protected rear seat passengers. Men predominated among the drivers; in the remaining groups of victims, the gender distribution was generally even. Among the participants in the accident were mainly people of working age. Injuries to the chest (26.5%), head (25.9%), abdomen (16.5%) prevailed among the associated injuries. Conclusion. A distinctive feature of injuries sustained as a result of a collision of a pedestrian or a car with another car with a relatively low speed of movement was an isolated injury to the bones of the pelvic girdle or lower extremities, both during pedestrian and intra-salon trauma. All the victims had injuries of the integumentary system of various localization in the form of subcutaneous hematomas and abrasions (158; 92.9%), bruised lacerations (96; 56.5%), stamp injuries (62; 36.5%). The main mechanism of pedestrian injury is the direct impact of the traumatic force with the formation of primary injuries in the form of bumper fractures of the shin bones (35.9%), hip (22.4%) and pelvis (10%).

Fitness Implications of Nonlethal Injuries in Scorpions: Females, but Not Males, Pay Reproductive Costs.

AbstractThe ability to detach a body part in response to a predation attempt is known as autotomy, and it is perhaps the most intensively studied form of nonlethal injury in animals. Although autotomy enhances survival, it may impose reproductive costs on both males and females. We experimentally investigated how autotomy affects the reproductive success of males and females of a scorpion species. Individuals of Ananteris balzani autotomize the last abdominal segments (the tail), losing the anus and leading to lifelong constipation, since regeneration does not occur. Although the male tail is used during courtship and sperm transfer, autotomy has no effect on male mating success. The combined effect of increased mortality and reduced fecundity resulted in autotomized females producing nearly 35% fewer offspring than intact females. In conclusion, the negative effects of tail autotomy are clearly sex dependent, probably because the factors that influence reproductive success in males and females are markedly different.

Effect of Short and Long Term Restraint Stress on the Histology of Liver, Kidney and Suprarenal Gland in Albino Mice during Postweaning Period

On exposure to stress and for the sake of survival, cells make adjustments with the changes in their environment to the physiologic needs and non-lethal pathologic injury. When the environmental changes are greater than the capacity of the cell to maintain normal homeostasis the cell undergoes acute cell injury. If the injury or insult is removed on time, or the cell can adapt and withstand the injury, the term reversible injury is applied. The processes of adaptation include decreasing or increasing their size, increasing their number, or changing the pathway of phenotypic differentiation of cells.
 In the present study, albino mice of postweaning age of BALB C strain (21 days old) were exposed to short term (5 days) and long term (21 days) restraint stress to evaluate any histological changes in the kidney, liver, and suprarenal gland.
 Mice subjected to long term stress showed in the kidney degeneration of the cells of the glomerulus and the convoluted tubules. In the liver, they showed congested sinusoids and the presence of some fatty change, whereas in the suprarenal gland mice subjected to 21 days of stress showed moderate hypertrophy and hyperplasia of the adrenal cortex with the presence of moderate lipoid deposits when compared to controls. The overall effect on short term stress was mild when compared to exposure to 21 days stress
 Long term stress causes degeneration in hepatic cells, infiltration in the liver, degeneration of glomerulus, Bowman’s capsule, convoluted tubules in the kidney which could lead to nephrotoxicity. In the suprarenal gland, long term stress induces hypertrophy of the adrenal cortex. These morphological changes can explain the impaired immunity which develops in organisms that are exposed to chronic stress.

At What Dose Can Total Body and Whole Abdominal Irradiation Cause Lethal Intestinal Injury Among C57BL/6J Mice?

Purpose and Methods:To investigate the doses of total body (TBI) and whole abdominal irradiation (WAI) induced lethal intestinal injury, healthy C57BL/6 J mice were divided randomly into 7 groups: control group; 6, 7, and 8 Gy TBI groups; and 5, 10, and 15 Gy WAI groups. The survival length, general conditions, body weight, daily food and water intake of the mice and the histopathological changes of small intestine were observed.Results:Lethal injury among C57BL/6 J mice was caused by ≥6 Gy TBI and 15 Gy WAI. Their body weight and food intake decreased, the structure of their small intestinal villi was destroyed, and the number of surviving crypts per circumference of the jejunum decreased in ≥6 Gy TBI groups and 15 Gy WAI group. The mice in the 10 Gy WAI group significantly lost weight within 5 days but recovered slowly thereafter. They also had poor appetite and reversibly damaged intestinal mucosa.Conclusions:Nonlethal intestinal injury could be induced by 10 Gy WAI, whereas lethal intestinal injury could be triggered by ≥6 Gy TBI and >15 Gy WAI in mice. Our results provided a basis for establishing radiation-induced intestinal injury models with C57BL/6 J mice.

Reproductive and energetic costs of injury in the mangrove tree crab

Nonlethal injury is a common and ubiquitous feature of marine systems and can result in altered growth and survival rates. Ecological theory predicts that injured animals should face an energetic tradeoff between investing in recovery vs. investing in reproduction. Possible impacts on reproduction may range in magnitude from very strong (elimination of reproduction), to intermediate (reduced number of offspring), to weak (reduced investment in each offspring). While this tradeoff is well established in terrestrial systems, it has received little attention in the marine environment, particularly in a way that quantitatively relates the degree of injury to the degree of reproductive impact. We examined injury via limb loss across 4 sites in the mangrove tree crab Aratus pisonii. We found that limb loss was highest at the site that was closest to roads and had the highest level of human presence, and conversely, injury was lowest at the site furthest from the road and with the lowest level of human presence. We found evidence that the quality of consumed food likely decreases with the number of limbs lost, but found no influence of limb loss on amount of food consumed or on energy storage. We show that limb loss reduced the number of eggs produced and that the mass of the ovary declined with the number of regenerating limbs, providing direct evidence for a tradeoff between reproduction and injury recovery. Further, our study therefore suggests that these impacts may increase with the level of human disturbance.

Rapid cold hardening: ecological relevance, physiological mechanisms and new perspectives.

Rapid cold hardening (RCH) is a type of phenotypic plasticity that allows ectotherms to quickly enhance cold tolerance in response to brief chilling (lasting minutes to hours). In this Review, we summarize the current state of knowledge of this important phenotype and provide new directions for research. As one of the fastest adaptive responses to temperature known, RCH allows ectotherms to cope with sudden cold snaps and to optimize their performance during diurnal cooling cycles. RCH and similar phenotypes have been observed across a diversity of ectotherms, including crustaceans, terrestrial arthropods, amphibians, reptiles, and fish. In addition to its well-defined role in enhancing survival to extreme cold, RCH also protects against nonlethal cold injury by preserving essential functions following cold stress, such as locomotion, reproduction, and energy balance. The capacity for RCH varies across species and across genotypes of the same species, indicating that RCH can be shaped by selection and is likely favored in thermally variable environments. Mechanistically, RCH is distinct from other rapid stress responses in that it typically does not involve synthesis of new gene products; rather, the existing cellular machinery regulates RCH through post-translational signaling mechanisms. However, the protective mechanisms that enhance cold hardiness are largely unknown. We provide evidence that RCH can be induced by multiple triggers in addition to low temperature, and that rapidly induced tolerance and cross-tolerance to a variety of environmental stressors may be a general feature of stress responses that requires further investigation.

The role of Glucagon-Like Peptide 1 Loading on periprocedural myocardial infarction During elective PCI (GOLD-PCI study): A randomized, placebo-controlled trial

The incretin hormone glucagon-like peptide 1 (GLP-1) has been shown to protect against lethal ischemia-reperfusion injury in animal models and against nonlethal ischemia reperfusion injury in humans. Furthermore, GLP-1 receptor agonists have been shown to reduce major adverse cardiovascular and cerebrovascular events (MACCE) in large-scale studies. We sought to investigate whether GLP-1 reduced percutaneous coronary intervention (PCI)-associated myocardial infarction (PMI) during elective PCI. The study was a randomized, double-blind controlled trial in which patients undergoing elective PCI received an intravenous infusion of either GLP-1 at 1.2 pmol/kg/min or matched 0.9% saline placebo before and during the procedure. Randomization was performed in 1:1 fashion, with stratification for diabetes mellitus. Six-hour cardiac troponin I (cTnI) was measured with a primary end point of PMI defined as rise ≫×5 upper limit of normal (280 ng/L). Secondary end points included cTnI rise and MACCE at 12 months. A total of 192 patients were randomized with 152 (79%) male and a mean age of 68.1 ± 8.9 years. No significant differences in patient demographics were noted between the groups. There was no difference in the rate of PMI between GLP-1 and placebo (9 [9.8%] vs 8 [8.3%], P = 1.0) or in the secondary end points of difference in median cTnI between groups (9.5 [0-88.5] vs 20 [0-58.5] ng/L, P = .25) and MACCE at 12 months (7 [7.3%] vs 9 [9.4%], P = .61). In this randomized, placebo-controlled trial, GLP-1 did not reduce the low incidence of PMI or abrogate biomarker rise during elective PCI, nor did it influence the 12-month MACCE rate which also remained low. Clinicaltrials.gov Number: NCT02127996https://clinicaltrials.gov/ct2/show/NCT02127996.

Rapid cold hardening protects against sublethal freezing injury in an Antarctic insect.

Rapid cold hardening (RCH) is a type of beneficial phenotypic plasticity that occurs on extremely short time scales (minutes to hours) to enhance insects' ability to cope with cold snaps and diurnal temperature fluctuations. RCH has a well-established role in extending lower lethal limits, but its ability to prevent sublethal cold injury has received less attention. The Antarctic midge, Belgica antarctica, is Antarctica's only endemic insect and has a well-studied RCH response that extends freeze tolerance in laboratory conditions. However, the discriminating temperatures used in previous studies of RCH are far below those ever experienced in the field. Here, we tested the hypothesis that RCH protects against non-lethal freezing injury. Larvae of B. antarctica were exposed to control (2°C), direct freezing (-9°C for 24 h) or RCH (-5°C for 2 h followed by -9°C for 24 h). All larvae survived both freezing treatments, but RCH larvae recovered more quickly from freezing stress and had a significantly higher metabolic rate during recovery. RCH larvae also sustained less damage to fat body and midgut tissue and had lower expression of two heat shock protein transcripts (hsp60 and hsp90), which is consistent with RCH protecting against protein denaturation. The protection afforded by RCH resulted in energy savings; directly frozen larvae experienced a significant depletion in glycogen energy stores that was not observed in RCH larvae. Together, these results provide strong evidence that RCH protects against a variety of sublethal freezing injuries and allows insects to rapidly fine-tune their performance in thermally variable environments.

TCT-599 The GlucagOn-like peptide 1 Loading During PCI (GOLD PCI) trial: 12-month clinical outcomes

Glucagon-like peptide 1 (GLP-1) is an incretin hormone, which has been shown to protect against non-lethal ischemia-reperfusion injury. We sought to investigate whether GLP-1 protected against peri-procedural myocardial infarction (PMI), when administered during elective PCI, and whether GLP-1

Abstract 23088: GLP-1 Loading During Percutaneous Coronary Intervention (GOLD PCI) trial

Introduction: Glucagon-like peptide 1 (7-36) amide (GLP-1) is an incretin hormone, which has been shown to protect against non-lethal cardiac ischemia-reperfusion injury. We sought to investigate whether GLP-1 protected against PCI-induced myocardial infarction (PMI) and attenuate cardiac troponin I (cTnI) release after elective PCI. Methods: A double-blind, randomised, placebo-control trial, stratified for diabetes mellitus, conducted in a single UK centre, administered an intravenous infusion of GLP-1 (1.2pmol/Kg/min) or saline to patients approximately 30-minutes before elective PCI. The primary endpoint was PMI defined as a cTnI elevation > 5xURL at 6-hours post-PCI. Secondary endpoints include, intra-procedural chest pain, TIMI flow and blush grade after PCI, rise in cTnI elevation and creatinine at 6-hours post-PCI and major adverse cardiovascular and cerebrovascular events (MACCE) at six months. Results: A CONSORT diagram for the study is shown in Figure 1. Of the 192 patients randomized, 152 (79%) were male, mean age 68.1±8.9 years. Patient demographics were similar between the groups. There was no inter-group difference in the incidence of PMI: GLP-1 9 (9.8%) vs. saline 8 (8.3%), p=0.28. Median [IQR] cTnI elevation between the groups was also similar: GLP-1 20 [0-88.5] vs. saline 10 [0-58.5] ng/L, p=0.28. Renal function was not impaired at 6 hours. Δ Creatinine was not significantly different. (GLP-1 -2.78±9.04 vs. saline -1.75±8.74 μmol/L, p=0.73). Other secondary end-point data will be available at time of presentation. Conclusion: GLP-1 did not confer cardioprotection against PMI after elective PCI, although the incidence of PMI in contemporary PCI is low.

Open Tracheostomy Gastric Acid Aspiration Murine Model of Acute Lung Injury Results in Maximal Acute Nonlethal Lung Injury.

Acid pneumonitis is a major cause of sterile acute lung injury (ALI) in humans. Acid pneumonitis spans the clinical spectrum from asymptomatic to acute respiratory distress syndrome (ARDS), characterized by neutrophilic alveolitis, and injury to both alveolar epithelium and vascular endothelium. Clinically, ARDS is defined by acute onset of hypoxemia, bilateral patchy pulmonary infiltrates and non-cardiogenic pulmonary edema. Human studies have provided us with valuable information about the physiological and inflammatory changes in the lung caused by ARDS, which has led to various hypotheses about the underling mechanisms. Unfortunately, difficulties determining the etiology of ARDS, as well as a wide range of pathophysiology have resulted in a lack of critical information that could be useful in developing therapeutic strategies. Translational animal models are valuable when their pathogenesis and pathophysiology accurately reproduce a concept proven in both in vitro and clinical settings. Although large animal models (e.g., sheep) share characteristics of the anatomy of human trachea-bronchial tree, murine models provide a host of other advantages including: low cost; short reproductive cycle lending itself to greater data acquisition; a well understood immunologic system; and a well characterized genome leading to the availability of a variety of gene deletion and transgenic strains. A robust model of low pH induced ARDS requires a murine ALI that targets mainly the alveolar epithelium, secondarily the vascular endothelium, as well as the small airways leading to the alveoli. Furthermore, a reproducible injury with wide differences between different injurious and non-injurious insults is important. The murine gastric acid aspiration model presented here using hydrochloric acid employs an open tracheostomy and recreates a pathogenic scenario that reproduces the low pH pneumonitis injury in humans. Additionally, this model can be used to examine interaction of a low pH insult with other pulmonary injurious entities (e.g., food particles, pathogenic bacteria).

Open Tracheostomy Gastric Acid Aspiration Murine Model of Acute Lung Injury Results in Maximal Acute Nonlethal Lung Injury

Open Tracheostomy Gastric Acid Aspiration Murine Model of Acute Lung Injury Results in Maximal Acute Nonlethal Lung Injury

The Effects of Crayfish Predation and Vegetation Cover on Tadpole Growth, Survival, and Nonlethal Injury

Abstract Predator–prey interactions play an important role in structuring larval anuran communities in ephemeral wetlands. The type of interaction often depends on the predator species and the complexity of the aquatic habitat. We experimentally evaluated the effects of Panhandle Crayfish (Procambarus evermanni) predation on larval Southern Leopard Frogs (Lithobates sphenocephalus) and larval Ornate Chorus Frogs (Pseudacris ornata). We performed separate experiments for each anuran species and used multiple vegetation treatments to examine whether vegetation could provide refugia from crayfish predation. Our results indicate that crayfish are effective predators of anuran larvae regardless of the amount of vegetation present. Encounters between tadpoles and crayfish often resulted in nonlethal tail injury for tadpoles, suggesting that crayfish predation is prominent in ephemeral wetland communities. Leopard frog tadpoles in predator treatments also grew larger than their counterparts in nonpredator treatm...

A rare autopsy case of traumatic rhabdomyolysis associated with intermittent assault

Traumatic rhabdomyolysis generally occurs after severe blunt trauma and is acute in onset, associated with severe disease, and potentially lethal. Accordingly, diagnosis of traumatic rhabdomyolysis in patients without massive subcutaneous or intramuscular hemorrhage is difficult, especially in the postmortem period, which is limited in terms of the availability of biochemical examination tools and accurate history of illness. To the best of our knowledge, there are no previous reports of death from traumatic rhabdomyolysis among individuals who did not pursue medical consultation. A previously healthy man in his early sixties had been punched and kicked several times in the previous 2months, but he had not gone to a hospital. He suddenly lost consciousness at his workplace approximately 5days after the most recent assault, and cardiopulmonary arrest occurred when the emergency service arrived. He died the same day, and a medicolegal autopsy was performed. Although several sites of minor subcutaneous and muscle hemorrhage were observed, the cause of death was unclear upon macroscopic assessment. Immunohistochemical staining revealed acute renal failure caused by rhabdomyolysis. We herein report a rare case of fatal traumatic rhabdomyolysis, seemingly associated with minor and apparently nonlethal muscle injury.

Molecular Imaging of Smoke-Induced Changes in Nuclear Factor-Kappa B Expression in Murine Tissues Including the Lung.

Many inflammatory responses are mediated by activation of the transcription factor, nuclear factor-kappa B (NF-κB), and a wide variety of human diseases involve abnormal regulation of its expression. In this investigation, we evaluated the effect of smoke inhalation injury on NF-κB expression in lung using two strains of NF-κB reporter mice. Groups of reporter mice with viral thymidine kinase (TK) or "fire fly" luciferase (Luc) genes under control by the NF-κB promoter (TK/NF-κB mice and Luc/NF-κB mice) were subjected to nonlethal smoke inhalation injury. Sham-treated animals served as controls. Twenty-four hours (each animal was injected intravenously with either 9-(4-18F-fluoro-3-[hydroxymethyl]butyl)guanine (FHBG) (~ 1.0 mCi) or luciferin (1.0 mg). One hour later, the TK/NF-κB mice were studied by micro-positron emission tomography (µ-PET) imaging using a Concord P4 µ-PET camera, and the Luc/NF-κB mice were studied by bioluminescence imaging with a charge-coupled device camera. The µ-PET data demonstrated that smoke injury produced massive increases in NF-κB expression (FHBG-standardized uptake value: 3.1 vs 0.0) 24 hours after smoke inhalation, which was reduced 48 hours after smoke inhalation, but still significantly different than the control. Qualitative analysis of the bioluminescence data revealed a remarkably similar effect of burn NF-κB luciferase expression in vivo. Biodistribution studies of FHBG uptake and luciferase activity in lung tissue demonstrated a similar increase 24 hours after injury, which was reduced 48 hours later, but still significantly higher than the sham. The present data with these models providing longitudinal imaging data on the same mouse may prove useful in the examination of the factors producing lung injury by smoke inhalation, as well as the treatment(s) for the damage produced with and without burn injury.