Changes in extracellular cytokines in predicting disease severity and final clinical outcome of patients with blunt chest trauma.

BACKGROUND: Chest trauma causes substantial morbidity and mortality and its severity is assessed using clinical diagnosis or scoring systems like Injury severity score (ISS) and thoracic trauma severity score (TTSS). Association of inflammatory cytokines with severity of disease and final clinical outcome is not clearly defined in patients with chest trauma. In this study, we thought to evaluate the inflammatory response in serum and bronchoalveolar lavage fluid (BALF) in chest trauma patients and correlate the level of extracellular cytokines with diseases severity and final outcome. METHODS: A total of 65 patients with blunt chest trauma and 30 healthy controls were enrolled in this prospective observational study. Assessment of inflammatory cytokines such as Interleukin (s) - IL-5, IL-13, IL-2, IL-6, IL-9, IL-1ß, IFN-γ, TNF-α, IL-17A, IL-17F,IL-4, IL-21 and IL-22 was performed in both serum and bronchoalveolar lavage fluid using 13-plex multiplex kit using fluorescence-encoded bead based immunoassays. RESULTS: A significantly higher level of IL-13, IL-2, IL-6, IL-9, IL-1ß, IFN-γ, TNF-α, IL-17A, IL-17F, IL-21 and IL-22 cytokines were observed in patients with blunt chest trauma compared to healthy controls. Level of IL-2, IL-6, IL-1ß and IL-17A was significantly raised in the patients with blunt chest trauma who had a fatal outcome during the hospital stay. An elevated cytokine response of IL-13, IL-4, and IL-21 was noted in the group of patients with high (>5) thoracic trauma severity score. CONCLUSION: Routine monitoring of the inflammatory cytokine level in patients with chest trauma may be used routinely. Longer prospective studies should be encouraged to determine the role of cytokines in patients with chest trauma in predicting the patient final clinical outcome.

Early local neutralization of CC16 in sepsis­induced ALI following blunt chest trauma leads to delayed mortality without benefitting overall survival.

Blunt thoracic trauma (TxT) is a common injury pattern in polytraumatized patients. When combined with a secondary trigger, TxT often results in acute lung injury (ALI), which negatively affects outcomes. Recent findings suggest that ALI is caused by both local and systemic inflammatory reactions. Club cell protein (CC)16 is an anti­inflammatory peptide associated with lung injury following TxT. Recently, the anti­inflammatory properties of endogenous CC16 in a murine model of TxT with subsequent cecal­ligation and puncture (CLP) as the secondary hit were demonstrated by our group. The present study aimed to determine whether CC16 neutralization improves survival following 'double­hit'­induced ALI. For this purpose, a total of 120 C57BL/6N mice were subjected to TxT, followed by CLP after 24 h. Sham­operated animals underwent anesthesia without the induction of TxT + CLP. CC16 neutralization was performed by providing a CC16 antibody intratracheally following TxT (early) or following CLP (late). Survival was assessed in 48 animals for 6 days after CLP. Sacrifice was performed 6 or 24 h post­CLP to evaluate the anti­inflammatory effect of CC16. The results revealed that CC16 neutralization enhanced pro­inflammatory CXCL1 levels, thereby confirming the anti­inflammatory characteristics of CC16 in this model. Early CC16 neutralization immediately following TxT significantly prolonged survival within 60 h; however, the survival rate did not change until 6 days post­trauma. Late CC16 neutralization did not provide any survival benefits. On the whole, the present study demonstrated that neutralizing CC16 confirmed its anti­inflammatory potential in this double­hit ALI model. Early CC16 neutralization prolonged survival within 60 h; however, no survival benefits were observed after 6 days post­CLP in any group.

Influence of obesity on remodeling of lung tissue and organization of extracellular matrix after blunt thorax trauma.

BACKGROUND: Previously, it has been shown that obesity is a risk factor for recovery, regeneration, and tissue repair after blunt trauma and can affect the rate of muscle recovery and collagen deposition after trauma. To date, lung tissue regeneration and extracellular matrix regulation in obese mice after injury has not been investigated in detail yet. METHODS: This study uses an established blunt thorax trauma model to analyze morphological changes and alterations on gene and protein level in lean or obese (diet-induced obesity for 16 ± 1 week) male C57BL/6 J mice at various time-points after trauma induction (1 h, 6 h, 24 h, 72 h and 192 h). RESULTS: Morphological analysis after injury showed lung parenchyma damage at early time-points in both lean and obese mice. At later time-points a better regenerative capacity of lean mice was observed, since obese animals still exhibited alveoli collapse, wall thickness as well as remaining filled alveoli structures. Although lean mice showed significantly increased collagen and fibronectin gene levels, analysis of collagen deposition showed no difference based on colorimetric quantification of collagen and visual assessment of Sirius red staining. When investigating the organization of the ECM on gene level, a decreased response of obese mice after trauma regarding extracellular matrix composition and organization was detectable. Differences in the lung tissue between the diets regarding early responding MMPs (MMP8/9) and late responding MMPs (MMP2) could be observed on gene and protein level. Obese mice show differences in regulation of extracellular matrix components compared to normal weight mice, which results in a decreased total MMP activity in obese animals during the whole regeneration phase. Starting at 6 h post traumatic injury, lean mice show a 50% increase in total MMP activity compared to control animals, while MMP activity in obese mice drops to 50%. CONCLUSIONS: In conclusion, abnormal regulation of the levels of extracellular matrix genes in the lung may contribute to an aberrant regeneration after trauma induction with a delay of repair and pathological changes of the lung tissue in obese mice.

Dexmedetomidine alleviates blunt chest trauma and hemorrhagic shock­resuscitation­induced acute lung injury through inhibiting the NLRP3 inflammasome.

Blunt chest trauma with hemorrhagic shock frequently induces pulmonary inflammation that leads to acute lung injury (ALI). The present study aimed to explore the protective effects of dexmedetomidine (Dex) in blunt chest trauma and hemorrhagic shock­resuscitation (THSR)­induced ALI by mediating nucleotide binding and oligomerization domain­like receptor family pyrin domain­containing protein 3 (NLRP3) inflammasome formation in rats. An ALI model in rats induced by THSR was constructed and Dex was administered intraperitoneally (5 µg/kg/h) immediately after blunt chest trauma. Blood samples were collected for the determination of proinflammatory factor levels, and lung tissue specimens were harvested for wet/dry (W/D) weight ratio, hematoxylin and eosin staining, and transmission electron microscopy analyses. Additionally, malondialdehyde (MDA), superoxide dismutase (SOD), lactate dehydrogenase (LDH) and myeloperoxidase (MPO) activity were evaluated, and the expression of protein in lung tissues was examined via western blot analysis. Compared with the sham group, pathological alterations in the ALI group and the W/D ratios were significantly increased. MDA, LDH and MPO activity, and the levels of interleukin (IL)­1ß, IL­18, IL­6 and tumor necrosis factor­α were significantly elevated. NLRP3, apoptosis­associated speck­like protein containing a caspase recruitment domain and caspase­1 expression was significantly increased. Conversely, Dex treatment significantly reversed these changes. The present study demonstrated that by reducing inflammatory responses, Dex exerted protective effects against THSR­ALI in rats, potentially via the inhibition of NLRP3 signaling pathways.

Contributing factors in the development of acute lung injury in a murine double hit model.

OBJECTIVES: Blunt chest (thoracic) trauma (TxT) is known to contribute to the development of secondary pulmonary complications. Of these, acute lung injury (ALI) is common especially in multiply injured patients and might not only be due to the direct trauma itself, but seems to be caused by ongoing and multifactorial inflammatory changes. Nevertheless, the exact mechanisms and contributing factors of the development of ALI following blunt chest trauma are still elusive. METHODS: 60 CL57BL/6N mice sustained either blunt chest trauma combined with laparotomy without further interventions or a double hit (DH) including TxT and cecal ligation puncture (CLP) after 24 h to induce ALI. Animals were killed either 6 or 24 h after the second procedure. Pulmonary expression of inflammatory mediators cxcl1, cxcl5, IL-1ß and IL-6, neutrophil infiltration and lung tissue damage using the Lung Injury Score (LIS) were determined. RESULTS: Next to a moderate increase in other inflammatory mediators, a significant increase in CXCL1, neutrophil infiltration and lung injury was observed early after TxT, which returned to baseline levels after 24 h. DH induced significantly increased gene expression of cxcl1, cxcl5, IL-1ß and IL-6 after 6 h, which was followed by the postponed significant increase in the protein expression after 24 h compared to controls. Neutrophil infiltration was significantly enhanced 24 h after DH compared to all other groups, and exerted a slight decline after 24 h. LIS has shown a significant increase after both 6 and 24 h compared to both control groups as well the late TxT group. CONCLUSION: Early observed lung injury with moderate inflammatory changes after blunt chest trauma recovered quickly, and therefore, may be caused by mechanical lung injury. In contrast, lung injury in the ALI group did not undergo recovery and is closely associated with significant changes of inflammatory mediators. This model may be used for further examinations of contributing factors and therapeutic strategies to prevent ALI.

CD28 Deficiency Ameliorates Thoracic Blast Exposure-Induced Oxidative Stress and Apoptosis in the Brain through the PI3K/Nrf2/Keap1 Signaling Pathway.

Blast exposure is a worldwide public health concern, but most related research has been focused on direct injury. Thoracic blast exposure-induced neurotrauma is a type of indirect injuries where research is lacking. As CD28 stimulates T cell activation and survival and contributes to inflammation initiation, it may play a role in thoracic blast exposure-induced neurotrauma. However, it has not been investigated. To explore the effects of CD28 on thoracic blast exposure-induced brain injury and its potential molecular mechanisms, a mouse model of thoracic blast exposure-induced brain injury was established. Fifty C57BL/6 wild-type (WT) and fifty CD28 knockout (CD28-/-) mice were randomly divided into five groups (one control group and four model groups), with ten mice (from each of the two models) for each group. Lung and brain tissue and serum samples were collected at 12 h, 24 h, 48 h, and 1 week after thoracic blast exposure. Histopathological changes were detected by hematoxylin-eosin staining. The expressions of inflammatory-related factors were detected by ELISA. Oxidative stress in the brain tissue was evaluated by determining the generation of reactive oxygen species (ROS) and the expressions of thioredoxin (TRX), malondialdehyde (MDA), SOD-1, and SOD-2. Apoptosis in the brain tissue was evaluated by TUNEL staining and the levels of Bax, Bcl-xL, Bad, Cytochrome C, and caspase-3. In addition, proteins of related pathways were also studied by western blotting and immunofluorescence. We found that CD28 deficiency significantly reduced thoracic blast exposure-induced histopathological changes and decreased the levels of inflammatory-related factors, including IL-1ß, TNF-α, and S100ß. In the brain tissue, CD28 deficiency also significantly attenuated thoracic blast exposure-induced generation of ROS and expressions of MDA, TRX, SOD-1, and SOD-2; lowered the number of apoptotic cells and the expression of Bax, cleaved caspase-3, Cytochrome C, and Bad; and maintained Bcl-xL expression. Additionally, CD28 deficiency significantly ameliorated thoracic blast exposure-induced increases of p-PI3K and Keap1 and the decrease of Nrf2 expression in the brain. Our results indicate that CD28 deficiency has a protective effect on thoracic blast exposure-induced brain injury that might be associated with the PI3K/Nrf2/Keap1 signaling pathway.

The Mitochondria-Targeted H2S-Donor AP39 in a Murine Model of Combined Hemorrhagic Shock and Blunt Chest Trauma.

Hemorrhagic shock (HS) accounts for 30% to 40% of trauma-induced mortality, which is due to multi-organ-failure subsequent to systemic hyper-inflammation, triggered by hypoxemia and tissue ischemia. The slow-releasing, mitochondria-targeted H2S donor AP39 exerted beneficial effects in several models of ischemia-reperfusion injury and acute inflammation. Therefore, we tested the effects of AP39-treatment in a murine model of combined blunt chest trauma (TxT) and HS with subsequent resuscitation. METHODS: After blast wave-induced TxT or sham procedure, anesthetized and instrumented mice underwent 1 h of hemorrhage followed by 4 h of resuscitation comprising an i.v. bolus injection of 100 or 10 nmol kg AP39 or vehicle, retransfusion of shed blood, fluid resuscitation, and norepinephrine. Lung mechanics and gas exchange were assessed together with hemodynamics, metabolism, and acid-base status. Blood and tissue samples were analyzed for cytokine and chemokine levels, western blot, immunohistochemistry, mitochondrial oxygen consumption (JO2), and histological changes. RESULTS: High dose AP39 attenuated systemic inflammation and reduced the expression of inducible nitric oxide synthase (iNOS) and IκBα expression in lung tissue. In the combined trauma group (TxT + HS), animals treated with high dose AP39 presented with the lowest mean arterial pressure and thus highest norepinephrine requirements and higher mortality. Low dose AP39 had no effects on hemodynamics, leading to unchanged norepinephrine requirements and mortality rates. CONCLUSION: AP39 is a systemic anti-inflammatory agent. In our model of trauma with HS, there may be a narrow dosing and timing window due to its potent vasodilatory properties, which might result in or contribute to aggravation of circulatory shock-related hypotension.

Pulmonary Arterial Thrombosis in a Murine Model of Blunt Thoracic Trauma.

Pulmonary thromboembolic events cause significant morbidity and mortality after severe trauma. Clinically, these lesions are believed to be emboli arising secondary to deep venous thrombosis (DVT) in the lower extremities. Recently, this notion has been challenged by clinical studies, showing that pulmonary clots arise after trauma in the absence of DVT. This suggests that pulmonary blood clots arise in situ via de novo thrombosis. In the present study, we characterize a murine weight-drop model of lateral blunt thoracic trauma. Our model demonstrates severe unilateral lung contusion injury with low (10%) mortality in the absence of extrapulmonary injury, after impact with a 50-g weight dropped from 45 cm height (657 J/m). At 24 h after injury, immunofluorescence and histological evidence revealed early pulmonary arterial thrombosis in the form of eccentric accumulation of fibrin and CD41 positive eosinophilic proteinaceous material, on both coup and contrecoup lung lobes of injured mice, indicating early thrombotic events both within and outside of the area of primary lung injury. Our model is ideal in that lateral impact enables greater impact energy to be applied to achieve significant lung contusion without significant mortality or extrapulmonary injury, and the model has additional translational value in creating thrombosis analogous to pulmonary embolism observed clinically after blunt thoracic trauma. To our knowledge, this is the first demonstration of de novo pulmonary thrombosis in a clinically translational model of blunt thoracic trauma, and supports challenges to current assumptions about the origin of pulmonary blood clots in the wake of severe traumatic injury.

A Molecular Method to Detect Wound Cells in Bloodstains Resultant of Sharp Force Injuries for Crime Scene Reconstruction.

Previous research by the authors on an animal model showed that bloodstains can contain additional information about their somatic origin in the form of wound cells. Bloodstains produced by a gunshot wound to the head were distinguished from bloodstains produced by a gunshot wound to the chest by testing the stains for a brain microRNA marker. In this study, the effectiveness of the technique was examined on blood drops shed externally from a stab wound to the liver of rat carcasses. Specifically, investigations were conducted on the liver microRNA marker, rno-mir-122-3p, with the QIAGEN miScript System, and PCR analysis. Between the two stabbing methods used, 67% of the scalpel blades and 57% of the blood drops tested positive for rno-mir-122-3p; however, other samples tested negative giving inconclusive results as to the wound-of-origin. The amount of the liver cells in the bloodstains appeared to be related to the extent of trauma.

Experimental blunt chest trauma-induced myocardial inflammation and alteration of gap-junction protein connexin 43.

OBJECTIVE: Severe blunt chest trauma in humans is associated with high mortality rates. Whereas lung tissue damage and lung inflammation after blunt chest trauma have extensively been investigated, the traumatic and posttraumatic effects on the heart remain poorly understood. Therefore, the purpose of this study was to define cardiac injury patterns in an experimental blunt chest trauma model in rats. METHODS: Experimental blunt chest trauma was induced by a blast wave in rats, with subsequent analysis of its effects on the heart. The animals were subjected either to a sham or trauma procedure. Systemic markers for cardiac injury were determined after 24 h and 5 days. Postmortem analysis of heart tissue addressed structural injury and inflammation 24 h and 5 days after trauma. RESULTS: Plasma levels of extracellular histones were elevated 24 h and 5 days after blunt chest trauma compared to sham-treated animals. In the heart, up-regulation of interleukin-1ß 24 h after trauma and increased myeloperoxidase activity 24 h and 5 days after trauma were accompanied by reduced complement C5a receptor-1 expression 24 h after trauma. Histological analysis revealed extravasation of erythrocytes and immunohistochemical analysis alteration of the pattern of the gap-junction protein connexin 43. Furthermore, a slight reduction of α-actinin and desmin expression in cardiac tissue was found after trauma together with a minor increase in sarcoplasmatic/endoplasmatic reticlulum calcium-ATPase (SERCA) expression. CONCLUSIONS: The clinically highly relevant rat model of blast wave-induced blunt chest trauma is associated with cardiac inflammation and structural alterations in cardiac tissue.

Role of biomarkers in acute traumatic lung injury.

In severely injured patients severe thoracic trauma is common and can significantly influence the outcome of these critically ill patients by increased rates of mainly pulmonary complications. Furthermore, patients who sustained thoracic trauma are at increased risk for Acute Lung Injury (ALI) or Adult Respiratory Distress Syndrome (ARDS). Therapeutic options are limited, basically consisting of prophylactic antibiotic therapy and changing patient's positions. It is known, that ALI and ARDS differ clinically and pathobiologically from ALI/ARDS caused by other reasons, but the exact pathology remains elusive. Due to that no reliable predictive or surveillance biomarkers could be established for clinical diagnosis and identification of patients at high risk for acute traumatic lung injury. Nevertheless, there are plenty of promising markers that need to be further elucidated in larger case numbers and multicenter studies. This article sums up the recent status of those promising clinical biomarkers.

Acute Alcohol Binge Deteriorates Metabolic and Respiratory Compensation Capability After Blunt Chest Trauma Followed by Hemorrhagic Shock-A New Research Model.

BACKGROUND: The clinical relevance of blunt (thoracic) chest trauma (TxT) and hemorrhagic shock is indisputable due to the high prevalence of this injury type, as well as its close association with mortality and/or preventable deaths. Furthermore, there is an ongoing discussion about the influence of alcohol in trauma patients. Thus, we established a model of TxT followed by hemorrhagic shock with resuscitation (H/R) in alcohol-intoxicated rats. METHODS: Depending on group allocation, 12 (subacute) or 2 (acute) hours before experimentation, the animals received a single oral dose of alcohol (ethanol [EtOH]) or saline (NaCl) followed by TxT, hemorrhagic shock (35 ± 3 mm Hg), and resuscitation (TxT + H/R). Arterial blood gas analyses and continuous monitoring of blood pressure were performed during the experimentation period. Survival during the experimentation procedure was determined. RESULTS: Subacute and acute EtOH group exhibited lower baseline mean arterial blood pressure values compared with the corresponding NaCl group, respectively. Both EtOH groups showed lower maximal bleed-out volume, which was necessary to induce hemorrhagic shock compared to NaCl groups, and the recovery during the resuscitation period was attenuated. During the experimentation in all groups, a trend to acidic pH was observed. Acute EtOH group showed lowest pH values compared to all other groups. Higher pCO2 values were observed in both EtOH groups. All groups developed negative base excess and decreasing HCO3- values until the end of hemorrhagic shock and showed increasing base excess and HCO3- values during resuscitation. Significantly higher mortality rate was found in the acute EtOH group. CONCLUSIONS: This study indicates that alcohol limits the metabolic and respiratory compensation capability, thereby promoting mortality.

Base excess, a useful marker in the prognosis of chest trauma in the geriatric population. / Exceso de bases, un marcador útil en el pronóstico del traumatismo torácico en la población geriátrica.

OBJECTIVE: To determine the usefulness of the determination of base excess in a cohort of elderly patients admitted to an intensive care unit (ICU) with a diagnosis of chest trauma. MATERIAL AND METHOD: Two hundred and forty-nine patients were included aged 65 years and over with a diagnosis of thoracic trauma who required admission to the ICU. We made a statistical analysis in order to determine the association of the first base excess levels with mortality during the unit stay. RESULTS: Two hundred and forty-nine patients, with a mean APACHE II score of 16.21±7.87 and 24.45±14.16 ISS. Mean ICU stay was 12.74±16.85 days and the mean hospital stay was 26.55±30.1 days. Statistical analysis showed an association with mortality in patients whose blood pressure was lower than 110mmHg on admission, with an OR=4.11 (95% CI 1.91 to 8.85) compared to patients with blood pressure between 110 and 140mmHg. Those patients who had base excess levels on admission of less than -6mmol/L also showed increased mortality compared to patients with higher levels, with an OR=3.12 (95% CI 1.51 to 6.42). CONCLUSIONS: The presence of a base excess level of less than -6 is associated with increased mortality in elderly patients with initial blood pressure between 110 and 140mmHg, diagnosed with thoracic trauma and who require admission to ICU. Routine measurement of this parameter in this population may show the clinical usefulness of assessing possible hidden hypoperfusion.

Role of the Purinergic Receptor P2XR4 After Blunt Chest Trauma in Cigarette Smoke-Exposed Mice.

Both acute and chronic lung injury are associated with up-regulation of the pulmonary expression of the purinergic receptors P2XR4 and P2XR7. Genetic deletion or blockade of P2XR7 attenuated pulmonary hyperinflammation, but simultaneous P2XR4 up-regulation compensated for P2XR7 deletion. Therefore, we tested the hypothesis whether genetic P2XR4 deletion would attenuate the pulmonary inflammatory response and thereby improve organ function after blunt chest trauma in mice with and without pretraumatic cigarette smoke (CS) exposure.After 3 weeks to 4 weeks of exposure to CS, anesthetized wildtype or P2XR4 mice (n = 32) underwent a blast wave-induced blunt chest trauma followed by 4 h of lung-protective mechanical ventilation, fluid resuscitation, and noradrenaline support to maintain mean arterial pressure >55 mm Hg. Hemodynamics, lung mechanics, gas exchange, and acid-base status were measured together with blood and tissue cytokine and chemokine concentrations, heme oxygenase-1, B-cell lymphoma-extra large (Bcl-xL), endogenous nuclear factor-κB inhibitor (IκBα) expression, nitrotyrosine formation, purinergic receptor expression, and histological scoring.Despite a significant increase in the histopathology score in both CS-exposed groups, neither CS exposure nor P2XR4 deletion had any significant effect on post-traumatic pulmonary function and inflammatory response. However, P2XR4 deletion was associated with attenuated impairment of glucose homeostasis and acid-base-status after CS exposure and chest trauma.In conclusion, genetic P2XR4 deletion failed to attenuate the acute post-traumatic pulmonary inflammatory response. The improved glucose homeostasis and acid-base-status after CS exposure in the P2XR4 group was possibly due to less alveolar hypoxia-induced right ventricular remodeling resulting in preserved liver metabolic capacity.

The Role of Cystathionine-γ-Lyase In Blunt Chest Trauma in Cigarette Smoke Exposed Mice.

Pretraumatic cigarette smoke (CS) exposure aggravates posttraumatic acute lung injury (ALI). Cystathionine-γ-lyase (CSE) protects against ALI and CS exposure-induced chronic obstructive lung disease (COPD). Therefore, we tested the hypothesis whether genetic CSE knockout (CSE) would aggravate posttraumatic ALI after CS exposure. After 3 to 4 weeks of CS exposure, anesthetized wild-type (WT) and CSE mice underwent blunt chest trauma, surgical instrumentation and 4 h of lung-protective mechanical ventilation. We measured hemodynamics, lung mechanics, gas exchange, metabolism, and acid-base status together with blood and tissue cytokine and chemokine levels, tissue expression of mediator proteins, parameters of oxidative and nitrosative stress, and histology. CSE mice without CS exposure showed higher cytokine and chemokine levels, and this was further enhanced by CS exposure, particularly in males. CS exposure in WT mice aggravated posttraumatic alveolar membrane thickening, dystelectasis, and inflammatory cell accumulation, which was associated with higher thoracopulmonary compliance. Pretraumatic CS exposure in CSE mice produced a similar response, except for less alveolar membrane thickening, most likely due to lung hyperinflation. CS-exposed WT mice showed the most pronounced metabolic acidosis, while CS exposure in CSE mice resulted in the lowest blood glucose levels. Urinary output and anesthesia rate were highest in male CS-exposed CSE animals. In conclusion, in murine acute-on-chronic pulmonary disease, CSE knockout aggravated posttraumatic inflammation, which was further worsened upon pretraumatic CS exposure, and this effect was particularly pronounced in males. Hence, maintaining CSE expression is critically important for stress adaptation during ALI and CS-induced COPD, most likely in a gender-dependent manner.

Modulation of the Redox Expression and Inflammation Response in the Critically Ill Polytrauma Patient with Thoracic Injury. Statistical Correlations between Antioxidant Therapy.

BACKGROUND: One of the major causes of mortality in the world is represented by multiple traumas. Thoracic trauma is commonly associated with polytraumas. A series of physiopathological complications follow polytraumas, leading to a significant decrease in the survival rate. As a result of injuries, significant quantities of free radicals (FR) are produced, responsible for oxidative stress (OS). To minimize the effects of OS, we recommend the administration of antioxidant substances. In this study we want to highlight statistically significant correlations between antioxidant therapy and a series of clinical variables. METHODS: This retrospective study included 132 polytrauma patients admitted to the ICU-CA between January 2013 and December 2014. The selection criteria were: injury severity score (ISS) ≥ 16, ≥ 18 years, presence of thoracic trauma (abbreviated injury scale, AIS ≥ 3). Eligible patients (n = 82) were divided into two groups: Group 1 (n = 32, antioxidant free, patients from 2013) and Group 2 (n = 50 antioxidant therapy, patients from 2014). Antioxidant therapy consisted in the administration of vitamin C (i.v.), vitamin B1 (i.v.), and N-acetylcysteine (i.v.). Clinical and biological tests were repeated until discharge from ICU-CA or death. RESULTS: Between Group 1 and Group 2 statistically significant differences were highlighted regarding the ISS score (p = 0.0030). 66% of patients from Group 2 were admitted at more than 24 hours after the trauma, in contrast to the patients from Group 1, where 62.5% were directly admitted to the ICU (p = 0.0114). Compared with the patients from Group 1, patients who received antioxidant therapy show improved parameters: leukocytes (p < 0.0001), platelets (p = 0.0489), urea (p = 0.0199), total bilirubin (p = 0.0111), alanine transaminase (p = 0.0010), lactat dehydrogenase (p < 0.0001). Between the two groups there were no statistically significant differences regarding the length of stay in the ICU-CA (p = 0.4697) and mortality (p = 0.1865). CONCLUSIONS: Following the study, we can affirm that due to the administration of antioxidant substances, posttraumatic complications are greatly reduced. Moreover, the administration of high dose of antioxidants remarkably improves the clinical status of the critical patient.

[Time-related expression of IL-6, IL-8 and TNF-alpha following explosive injury to rabbit's chest].

OBJECTIVE: To explore the relationship between the expression changes of cytokines, interleukin-6 (IL-6), interleukin-8(IL-8), and tumor necrosis factor-alpha (TNF-alpha), and the wound time following explosive injury to rabbit's chest. METHODS: The rabbit's model of explosive injury was established. The expression levels of IL-6, IL-8 and TNF-alpha in the plasma were detected by ELISA method at different wound time (0.5-12h). RESULTS: The level of IL-6 increased at 3h after wounding and reached peak at 6 h. The level of IL-8 increased at 1 h and reached peak at 6 h. The level of TNF-alpha increased at 0.5 h and reached peak at 3 h. CONCLUSION: IL-6, IL-8 and TNF-alpha have a time-related expression after explosive injury.

Captopril protects against burn-induced cardiopulmonary injury in rats.

BACKGROUND: This study was designed to determine the possible protective effect of captopril treatment against oxidative damage in heart and lung tissues induced by burn injury. METHODS: Under ether anesthesia, the shaved dorsum of Wistar albino rats was exposed to 90°C water bath for 10 seconds. Captopril was administered intraperitoneally (10 mg/kg) after the burn injury and repeated twice daily. In the sham group, the dorsum was dipped in a 25°C water bath for 10 seconds. At the end of the 24 hours, echocardiographic recordings were performed, then animals were decapitated and heart and lung tissue samples were taken for the determination of tumor necrosis factor-α (TNF-α) as a pro-inflammatory cytokine, malondialdehyde and glutathione levels and myeloperoxidase, caspase-3, and Na+,K+-ATPase activity in addition to the histological analysis. RESULTS: Burn injury caused significant alterations in left ventricular function. In heart and lung tissues, TNF-α and malondialdehyde levels and myeloperoxidase and caspase-3 activities were found to be increased, while glutathione levels and Na+, K+-ATPase activity were decreased due to burn injury. Captopril treatment significantly elevated the reduced glutathione level and Na+, K+-ATPase activity, and decreased cytokine and malondialdehyde levels and myeloperoxidase and caspase-3 activities. CONCLUSION: Captopril prevents burn-induced damage in heart and lung tissues and protects against oxidative organ damage.

A molecular method to correlate bloodstains with wound site for crime scene reconstruction.

Bloodstain pattern analysis to determine the wound-of-origin of bloodstains is problematic with nonspecific patterns. In this proof-of-concept study, the authors examined a molecular approach to correlate bloodstains with injuries using the rat as a model. Specifically, investigations were conducted on the rat brain marker, rno-miR-124-3p, with the QIAGEN miScript System and real-time PCR analysis. Rno-miR-124-3p was detected in brain homogenates diluted 100,000 times; in 3-week-old, room temperature stored, simulated brain-blood stains; and in bloodstains from head gunshot wounds collected with swabs and subsequently frozen for 9-18 months; however, rno-miR-124-3p was not detected in whole blood. Proof-of-principle was demonstrated by the ability to distinguish bloodstains from a gunshot wound to the head versus bloodstains from a gunshot wound to the chest, by the testing of otherwise identical bloodstains from the two patterns for the presence of the marker. The results suggest a viable approach to a longstanding problem in casework.

Time-related expression of IL-6, IL-8 and TNF-alpha following explosive injury to rabbit's chest / 法医学杂志

OBJECTIVE@#To explore the relationship between the expression changes of cytokines, interleukin-6 (IL-6), interleukin-8(IL-8), and tumor necrosis factor-alpha (TNF-alpha), and the wound time following explosive injury to rabbit's chest.@*METHODS@#The rabbit's model of explosive injury was established. The expression levels of IL-6, IL-8 and TNF-alpha in the plasma were detected by ELISA method at different wound time (0.5-12h).@*RESULTS@#The level of IL-6 increased at 3h after wounding and reached peak at 6 h. The level of IL-8 increased at 1 h and reached peak at 6 h. The level of TNF-alpha increased at 0.5 h and reached peak at 3 h.@*CONCLUSION@#IL-6, IL-8 and TNF-alpha have a time-related expression after explosive injury.