Effects of Bosentan on Hypoxia, Inflammation and Oxidative Stress in Experimental Blunt Thoracic Trauma Model.

Background and Objectives: In this study, we aimed to investigate the effects of bosentan, an endothelin receptor antagonist, on endothelin-1 (ET-1), hypoxia-inducible factor-1 (HIF-1), nuclear factor-kappa B (NF-κB), and tumor necrosis factor (TNF)-α as inflammation markers, pro-oxidant antioxidant balance (PAB), and total antioxidant capacity (TAC) levels as oxidative stress parameters in lung tissues of rats in an experimental model of pulmonary contusion (PC) induced by blunt thoracic trauma. Materials and Methods: Thirty-seven male Sprague-Dawley rats were divided into five groups. C: The control group (n = 6) consisted of unprocessed and untreated rats. PC3 (n = 8) underwent 3 days of PC. PC-B3 (n = 8) received 100 mg/kg bosentan and was given orally once a day for 3 days. The PC7 group (n = 7) underwent 7 days of PC, and PC-B7 (n = 8) received 100 mg/kg bosentan and was given orally once a day for 7 days. Results: ET-1, NF-κB, TNF-α, HIF-1α, and PAB levels were higher, while TAC activity was lower in all groups compared with the control (p < 0.05). There was no significant difference in ET-1 and TNF-α levels between the PC-B3 and PC-B7 groups and the control group (p < 0.05), while NF-κB, HIF-1α, and PAB levels were still higher in both the PC-B3 and PC-B7 groups than in the control group. Bosentan decreased ET-1, NF-κB, TNF-α, HIF-1α, and PAB and increased TAC levels in comparison to the nontreated groups (p < 0.05). Conclusions: Bosentan decreased the severity of oxidative stress in the lungs and reduced the inflammatory reaction in rats with PC induced by blunt thoracic trauma. This suggests that bosentan may have protective effects on lung injury mechanisms by reducing hypoxia, inflammation, and oxidative stress. If supported by similar studies, bosentan can be used in both pulmonary and emergency clinics to reduce ischemic complications, inflammation, and oxidative stress in some diseases that may be accompanied by ischemia.

Low-molecular-weight heparin is associated with lower venous thromboembolism events than factor Xa inhibitors in patients with severe blunt trauma: a cohort study from the Trauma Quality Improvement Program.

BACKGROUND: Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), is a common complication of major trauma. Pharmacological VTE prophylactics are widely used, and low-molecular-weight heparin (LMWH) is recommended. Factor Xa inhibitors are increasingly being used for VTE prophylaxis in both medical and surgical patients. Evidence comparing LMWH and factor Xa inhibitors as VTE prophylactics for severe blunt trauma is lacking. This study aims to compare the efficacy and safety of factor Xa inhibitors and LMHW in VTE prophylaxis. MATERIALS AND METHODS: Patients with severe blunt trauma who received LMWH or a factor Xa inhibitor for VTE prophylaxis in the Trauma Quality Improvement Program between 2017 and 2019 were included. The comparison was performed after using propensity score matching. The outcomes included mortality and incidence of DVT, PE, post-prophylactics haemorrhage control procedures and length of stay. RESULTS: After 2:1 propensity score matching, 1128 patients ( n =752, LMHW group; n =376, factor Xa inhibitor group) were included in the analysis. Patients in the LMWH group had fewer VTE events than those in the factor Xa inhibitor group (DVT, 3.7% vs. 7.2%, P =0.013; PE, 0.4% vs. 3.2%, P <0.001). VTE risk was higher in the factor Xa group (DVT: odds ratio, 1.97; 95% CI, 1.12-3.44; P =0.018 and PE: odds ratio, 9.65; 95% CI, 2.91-44.12; P =0.001). The mortality rate was higher in the LMWH group; however, there was no significant difference (4.0% vs. 1.9%; P =0.075). The difference in the risk of undergoing haemorrhage control surgery after VTE prophylaxis between both groups was insignificant (0.3% vs. 0.0%; P =0.333). CONCLUSIONS: LMWH was associated with a lower risk of VTE than factor Xa inhibitors in patients with severe blunt trauma. The mortality rate was higher in the LMWH group; however, there was no statistically significant difference observed.

TXA does not affect levels of TBI-related biomarkers in blunt TBI with ICH: A secondary analysis of the prehospital TXA for TBI trial.

BACKGROUND: Brain specific biomarkers such as glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCH-L1), and microtubule-associated protein-2 (MAP-2) have been identified as tools for diagnosis in traumatic brain injury (TBI). Tranexamic acid (TXA) has been shown to decrease mortality in patients with intracranial hemorrhage (ICH). The effect of TXA on these biomarkers is unknown. We investigated whether TXA affects levels of GFAP, UCH-L1, and MAP-2, and whether biomarker levels are associated with mortality in patients receiving TXA. METHODS: Patients enrolled in the prehospital TXA for TBI trial had GFAP, UCHL-1 and MAP-2 levels drawn at 0 hour and 24 hours postinjury (n = 422). Patients with ICH from blunt trauma with a GCS <13 and SBP >90 were randomized to placebo, 2 g TXA bolus, or 1 g bolus +1 g/8 hours TXA infusion. Associations of TXA and 24-hour biomarker change were assessed with multivariate linear regression. Association of biomarkers with 28-day mortality was assessed with multivariate logistic regression. All models were controlled for age, GCS, ISS, and AIS head. RESULTS: Administration of TXA was not associated with a change in biomarkers over 24 hours postinjury. Changes in biomarker levels were associated with AIS head and age. On admission, higher GFAP (odds ratio [OR], 1.75; confidence interval [CI], 1.31-2.38; p < 0.001) was associated with increased 28-day mortality. At 24 hours postinjury, higher levels of GFAP (OR, 2.09; CI, 1.37-3.30; p < 0.001 and UCHL-1 (OR, 2.98; CI, 1.77-5.25; p < 0.001) were associated with mortality. A change in UCH levels from 0 hour to 24 hours postinjury was also associated with increased mortality (OR, 1.68; CI, 1.15-2.49; p < 0.01). CONCLUSION: Administration of TXA does not impact change in GFAP, UCHL-1, or MAP-2 during the first 24 hours after blunt TBI with ICH. Higher levels of GFAP and UCH early after injury may help identify patients at high risk for 28-day mortality. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

When is it safe to start venous thromboembolism prophylaxis after blunt solid organ injury? A prospective American Association for the Surgery of Trauma multi-institutional trial.

BACKGROUND: The optimal time to initiate venous thromboembolism (VTE) chemoprophylaxis (VTEp) after blunt solid organ injury remains controversial, as VTE mitigation must be balanced against bleeding promulgation. Evidence from primarily small, retrospective, single-center work suggests that VTEp ≤48 hours is safe and effective. This study was undertaken to validate this clinical practice. METHODS: Blunt trauma patients presenting to 19 participating trauma centers in North America were screened over a 1-year study period beginning between August 1 and October 1, 2021. Inclusions were age older than 15 years; ≥1 liver, spleen, or kidney injury; and initial nonoperative management. Exclusions were transfers, emergency department death, pregnancy, and concomitant bleeding disorder/anticoagulation/antiplatelet medication. A priori power calculation stipulated the need for 1,158 patients. Time of VTEp initiation defined study groups: Early (≤48 hours of admission) versus Late (>48 hours). Bivariate and multivariable analyses compared outcomes. RESULTS: In total, 1,173 patients satisfied the study criteria with 571 liver (49%), 557 spleen (47%), and 277 kidney injuries (24%). The median patient age was 34 years (interquartile range, 25-49 years), and 67% (n = 780) were male. The median Injury Severity Score was 22 (interquartile range, 14-29) with Abbreviated Injury Scale Abdomen score of 3 (interquartile range, 2-3), and the median American Association for the Surgery of Trauma grade of solid organ injury was 2 (interquartile range, 2-3). Early VTEp patients (n = 838 [74%]) had significantly lower rates of VTE (n = 28 [3%] vs. n = 21 [7%], p = 0.008), comparable rates of nonoperative management failure (n = 21 [3%] vs. n = 12 [4%], p = 0.228), and lower rates of post-VTEp blood transfusion (n = 145 [17%] vs. n = 71 [23%], p = 0.024) when compared with Late VTEp patients (n = 301 [26%]). Late VTEp was independently associated with VTE (odd ratio, 2.251; p = 0.046). CONCLUSION: Early initiation of VTEp was associated with significantly reduced rates of VTE with no increase in bleeding complications. Venous thromboembolism chemoprophylaxis initiation ≤48 hours is therefore safe and effective and should be the standard of care for patients with blunt solid organ injury. LEVEL OF EVIDENCE: Therapeutic and Care Management; Level III.

Effects of amifostine against blunt chest trauma-induced cardiac injury in rats.

BACKGROUND: This study aimed to examine whether two different doses of dexamethasone (DXM), which is a corticosteroid, and amifostine (AMI), which reduces cumulative tissue toxicity induced by cisplatin in advanced-stage cancer patients, have ameliorative effects on pathologic changes associated with cardiac contusion (CC) induced in rats. METHODS: Forty-two Wistar albino rats were equally divided into six groups (n=7): C, CC, CC+AMI 400, CC+AMI 200, CC+AMI+DXM, and CC+DXM. Tomography images and electrocardiographic analyzes were performed, mean arterial pressure was measured from the carotid artery, and blood and tissue samples were obtained for histopathological and biochemical analyses after trauma-induced CC. RESULTS: While the total oxidant status and disulfide parameters in the cardiac tissue and serum were significantly higher (p<0.05), the total antioxidant status, total thiol, and native thiol parameters were significantly lower (p<0.01) in rats with trauma-induced CC. The most frequently observed finding in the electrocardiography analyze was ST elevation. CONCLUSION: According to evaluation based on histological, biochemical, and electrocardiographic examinations, we believe that only 400 mg/kg dose of AMI or DXM can be effective in the treatment of myocardial contusion in rats. Evaluation based on histological findings.

Timing of venous thromboembolism chemoprophylaxis using objective hemoglobin criteria in blunt solid organ injury.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of early venous thromboembolism (VTE) chemoprophylaxis following blunt solid organ injury. METHODS: A retrospective review of patients was performed for patients with blunt solid organ injury between 2009-2019. Enoxaparin was initiated when patients had <1g/dl Hemoglobin decline over a 24 h period. These patients were then categorized by initiation: ≤48 h and >48 h. RESULTS: There were 653 patients: 328 (50.2%) <48 h and 325 (49.8%) ≥48 h. Twenty-nine (4.4%) developed VTE. Patients in ≥48 h group suffered more frequent VTE events (6.5% vs 2.4%, p = 0.021). Non-operative failure occurred in 6 patients (1.9%) in ≥48 h group, and 5 patients (1.5%) < 48 h group. Blood transfusion following chemophrophylaxis initiation was required in 69 (21.3%) in ≥48 h group, and 46 (14.0%) in < 48 h group, occurring similarly between groups (p=0.021). CONCLUSION: Stable hemoglobin in the first 24 h is an efficacious, objective measure that allows early initiation of VTE chemoprophylaxis in solid organ injury. This practice is associated with earlier initiation of and fewer VTE events.

Traumatic hyphema in a patient with severe hemophilia A: Clinical features and management.

PURPOSE: To describe a case of traumatic hyphema in a patient with severe hemophilia A. CASE: We present a case of a 16-year-old boy with severe hemophilia A who presented to our ophthalmology department with total hyphema and elevated intraocular pressure 3 days after a history of blunt ocular trauma on his right eye. Due to the persistent intraocular pressure elevation and total hyphema despite medical intervention, an early anterior chamber washout was performed with the replacement of factor VIII preoperatively and postoperatively. Re-bleeding or any other complications were not experienced during surgery or postoperatively. At the first postoperative week, 20/20 visual acuity and a normal intraocular pressure without antiglaucoma medication was retained and remained stable during the 6-month follow-up. CONCLUSION: In such cases with hemophilia A, traumatic hyphema, and intraocular pressure elevation despite medical intervention, an early surgical clot removal under intense factor VIII replacement could be performed. In the early postoperative period, factor replacement should be resumed in order to avoid re-bleeding.

Early vasopressor administration in pediatric blunt liver and spleen injury: An ATOMAC+ study.

BACKGROUND: No prior studies have examined the outcomes of early vasopressor use in children sustaining blunt liver or spleen injury (BLSI). METHODS: A planned secondary analysis of vasopressor use from a 10-center, prospective study of 1004 children with BLSI. Inverse probability of treatment weighting (IPTW) was used to compare patients given vasopressors <48 h after injury to controls based on pretreatment factors. A logistic regression was utilized to assess survival associated with vasopressor initiation factors on mortality and nonoperative management (NOM) failure. RESULTS: Of 1004 patients with BLSI, 128 patients were hypotensive in the Pediatric Trauma Center Emergency Department (ED); 65 total patients received vasopressors. Hypotension treated with vasopressors was associated with a sevenfold increase in mortality (AOR = 7.6 [p < 0.01]). When excluding patients first given vasopressors for cardiac arrest, the risk of mortality increased to 11-fold (AOR = 11.4 [p = 0.01]). All deaths in patients receiving vasopressors occurred when started within the first 12 h after injury. Vasopressor administration at any time was not associated with NOM failure. CONCLUSION: After propensity matching, early vasopressor use for hypotension in the ED was associated with an increased risk of death, but did not increase the risk of failure of NOM. LEVEL OF EVIDENCE: Level III prognostic and epidemiological, prospective.

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.

Treatment of blunt cerebrovascular injuries: Anticoagulants or antiplatelet agents?

BACKGROUND: Blunt cerebrovascular injury (BCVI) is associated with cerebrovascular accidents (CVA). Early therapy with antiplatelet agents or anticoagulants is recommended. There are limited data comparing the effectiveness of these treatments. The aim of our study was to compare outcomes between BCVI patients who received anticoagulants versus those who received antiplatelet agents. METHODS: We performed an (2011-2015) analysis of the Nationwide Readmission Database and included all adult trauma patients 18 years or older who had an isolated BCVI (other body regions Abbreviated Injury Scale [AIS] < 3). Head injury patients or those who developed a CVA during the index admission were excluded. Patients were stratified into anticoagulants and antiplatelet agents. Propensity score matching was performed (1:1 ratio) to control for demographics, comorbidities, BCVI grade, distribution, and severity of injuries. Outcomes were readmission with CVA and mortality within 6 months. RESULTS: A total of 725 BCVI patients were identified. A matched cohort of 370 patients (antiplatelet agents, 185; anticoagulants, 185) was obtained. Mean age was 50 ± 15 years, neck AIS was 3 (3,4), and Injury Severity Score was 12 (9-17). The majority of the patients (69%) had high-grade BCVI (AIS ≥ 3). Overall, 3.7% were readmitted with CVA and 3% died within 6 months. Patients who received anticoagulants had a lower rate of readmission with CVA (1.8% vs. 5.72%; p = 0.03), and a lower rate of 6-month mortality (1.3% vs. 4.9%; p = 0.03). There was no significant difference between the two groups reading the median time to stroke (9 days vs. 6 days; p = 0.12). CONCLUSION: The BCVI patients on CVA prophylaxis for BCVI have a 3.7% rate of stroke after discharge. Compared with antiplatelet agents, anticoagulants are associated with lower rates of CVA in the first 6-month postdischarge. Further studies are required to identify the optimal agent to prevent CVA in this high-risk subset of trauma patients. LEVEL OF EVIDENCE: Therapeutic, level IV.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FINDINGS IN A CASE OF CHOROIDAL NEOVASCULARIZATION SECONDARY TO TRAUMATIC CHOROIDAL RUPTURE.

BACKGROUND/PURPOSE: To document by optical coherence tomography angiography, the onset of a choroidal neovascularization (CNV) secondary to traumatic choroidal rupture and describe its changes after an intravitreal injection of bevacizumab. METHODS: Case report. RESULTS: A 20-year-old woman presented referring vision loss after a blunt ocular trauma in her left eye. The patient underwent a complete ophthalmic examination. Best-corrected visual acuity was 20/200. Fundus examination, fluorescein angiography, indocyanine green angiography, and optical coherence tomography displayed a choroidal rupture with no evidence of CNV. Optical coherence tomography angiography showed the choroidal rupture as a line of choriocapillaris rarefaction because of the mechanical damage. Six months later, best-corrected visual acuity decreased to 20/300; optical coherence tomography angiography displayed the growth of a CNV, characterized by a tangled vascular network. After one intravitreal injection of bevacizumab, optical coherence tomography angiography documented a contraction of the CNV. CONCLUSION: Optical coherence tomography angiography is a useful imaging technique for the diagnosis and follow-up of patients with choroidal ruptures. Anti-vascular endothelial growth factor agents represent an effective therapy for the treatment of CNVs secondary to this affection.

Investigation of Bosentan's Effects on Pulmonary Contusion Created by Blunt Thoracic Trauma in Rats.

INTRODUCTION: Bosentan is an endothelin-1 receptor antagonist with anti-inflammatory, antioxidant, and antiproliferative effects. We aimed to evaluate its effects on lung tissue in a pulmonary contusion (PC) model. MATERIALS AND METHODS: The rats were randomly divided into five groups: PC3: PC evaluated on the 3rd day (n = 8), PC-B3: PC enteral bosentan 100 mg/kg/day, for 3 days (n = 8), PC7: PC evaluated on the 7th day (n = 7), PC-B7: PC 7 days bosentan 100 mg/kg/day, for 7 days (n = 8), C: control (n = 6). Unilateral lung contusion was created by dropping a metal weight onto the chest. The rats were sacrificed on the 3rd or the 7th days. The lung tissue was evaluated histopathologically for alveolar edema, congestion, and leukocyte infiltration, biochemically for malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO) levels, and immunohistochemically for inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), and apoptosis scores. RESULTS: Alveolar edema, congestion, and leukocyte infiltration scores were increased in all groups compared with the control group (p < 0.05) and decreased in bosentan-treated groups compared with the relevant nontreated groups (p < 0.05). Fibrosis was observed only in PC7 and PC-B7 groups. Bosentan did not have any effect on fibrosis development. iNOS and eNOS levels were higher in all groups compared with the control (p < 0.05) without a difference in the nontreated versus treated groups (p > 0.05). Bosentan treatment caused decreased MDA and increased SOD levels in comparison to the nontreated groups (p < 0.05). Tissue NO levels did not show any significant difference among groups. PC groups had higher levels of apoptosis compared with the control group (p < 0.05). The degree of apoptosis decreased in bosentan-treated groups compared with the nontreated groups (p < 0.05). CONCLUSION: PC causes progressive lung tissue damage. Bosentan reduced leukocyte infiltration and alveolar edema and congestion caused by PC. It also decreased MDA levels and increased SOD levels. Bosentan prevents tissue damage by inhibiting acute inflammatory response and reduces oxidative stress secondary to inflammation. It has therapeutic effects on apoptosis.

TRAUMATIC MACULAR HOLE CLOSURE AND VISUAL IMPROVEMENT AFTER TOPICAL NONSTEROIDAL ANTIINFLAMMATORY DRUG TREATMENT.

PURPOSE: To report a case of pediatric traumatic macular hole that closed with visual improvement after treatment with topical ketorolac. METHODS: Retrospective case report. RESULTS: A 15-year-old girl presented with persistent left blurred vision after being hit with a soccer ball 2 months before. Visual acuity was 20/40 with a full-thickness macular hole with cystoid macular edema. After treatment with ketorolac 0.4% four times a day for a month, the hole closed with resolution of the cystoid macular edema but some remaining subretinal fluid. The ketorolac was tapered over the following month, and the subretinal fluid resolved during the subsequent months. At 10 months after initial presentation, patient's vision was 20/20 with a normal foveal contour, no subretinal fluid, and minimal ellipsoid zone disruption. CONCLUSION: Topical nonsteroidal antiinflammatory drug treatment may play a role in the resolution of traumatic macular holes with cystoid macular edema.

Initial Harm Reduction by N-Acetylcysteine Alleviates Cartilage Degeneration after Blunt Single-Impact Cartilage Trauma in Vivo.

Joint injuries are highly associated with the development of post-traumatic osteoarthritis. Previous studies revealed cell- and matrix-protective effects of N-acetylcysteine (NAC) after ex vivo cartilage trauma, while chondroanabolic stimulation with bone morphogenetic protein 7 (BMP7) enhanced type II collagen (COL2) expression. Here, as a next step, we investigated the combined and individual efficacy of intra-articular antioxidative and chondroanabolic treatment in a rabbit in vivo cartilage trauma model. Animals were randomly divided into group A (right joint: trauma (T); left joint: T+BMP7) and group B (right joint: T+NAC; left joint: T+BMP7+NAC). Condyles were impacted with the use of a spring-loaded impact device to ensure defined, single trauma administration. After 12 weeks, histopathological analysis was performed and the presence of matrix metalloproteinase 13 (MMP-13) and COL2 was assessed. Trauma-induced hypocellularity, MMP-13 expression, and cell cluster formation were reduced in NAC-treated animals. In contrast, BMP7 further increased cluster formation. Moreover, synovial concentrations of COL2 carboxy propeptide (CPII) and proteoglycan staining intensities were enhanced in NAC- and NAC+BMP7-treated joints. For the first time, the efficacy of NAC regarding early harm reduction after blunt cartilage trauma was demonstrated in vivo. However, parallel administration of BMP7 was not significantly superior compared to NAC alone.

Cardioprotective effect of caffeic acid phenethyl ester on cardiac contusion following blunt chest trauma in rats.

We investigated the effects of caffeic acid phenethyl ester (CAPE) on cardiac damage after blunt chest injury. Forty male adult Wistar albino rats were divided into four groups; control, cardiac contusion, cardiac contusion + CAPE, and CAPE. CAPE, 10 mmol/kg, was administered intraperitoneally for 7 days following cardiac contusion. Heart tissue and blood were obtained at the end of the experimental period. Cardiac histopathology was determined using hematoxylin & eosin (H & E) staining. Expression of tumor necrosis factor-alpha (TNF-α) in cardiomyocytes was determined using immunohistochemistry. Cardiac apoptosis was determined using the TUNEL method. Serum creatine kinase (CK), creatine kinase-muscle/brain (CK-MB) and lactate dehydrogenase (LDH) levels were determined using spectrophotometric methods. The serum cardiac troponin I (C-TI) level was measured using the ELISA method. Myofibril loss was detected in the cardiomyocytes of the cardiac contusion group. Increased apoptosis and TNF-α expression were observed in the cardiac contusion group compared to the control group. Increased CK, CK-MB, LDH and C-TI levels were found in the cardiac contusion group. We found that CAPE administration improved myocardial function. Compared to the cardiac contusion group, CK, CK-MB, LDH and C-TI levels decreased significantly in the cardiac contusion + CAPE group. Administration of CAPE significantly inhibited apoptosis and cardiac TNF-α expression. Our findings demonstrate the therapeutic effects of CAPE for cardiac contusion damage after blunt chest trauma.

Anti-inflammatory and antioxidant effect of melatonin on recovery from muscular trauma induced in rats.

In recent decades, the number of people who practice sports has grown exponentially, increasing the number of muscular injuries. Trauma injury occurs when the muscle is exposed to a sudden compression force. Melatonin (MLT) has often been cited in the literature as a potent antioxidant and anti-inflammatory agent. This study was designed to evaluate MLT action on muscle tissue in Wistar rats in an experimental model of muscle trauma. Twenty-eight Wistar rats were used, divided into four groups: CO (Control), CO + MLT (Control + Melatonin), T (Trauma) and T + MLT (Trauma + Melatonin). MLT (20 mg/kg) was administered (ip) daily at dusk until day 7. The trauma occurred on day 1, 2 h before the first MLT application. On day 8, muscle tissue was collected for histological analysis (HE), immunohistochemistry (TNF-α and NFκB), evaluation of oxidative stress through analysis of lipoperoxidation by TBARS and activity of SOD and GPx enzymes, and analysis of nitrites and nitrates. In the evaluation of TBARS and SOD, we observed a significant increase in the T group and a significant decrease in the T + MLT group. In the evaluation of GPx, there was a significant increase in the T group and a significant decrease in the T + MLT group. The histological analysis of muscle tissue revealed structural changes of muscle fibers and inflammatory infiltrate in the T group but a decrease in this damage in the T + MLT group. In the immunohistochemical evaluation, increased expression of TNFα and NFκB proteins in the T group was observed and a significant decrease of this expression in the T + MLT group. MLT was shown to attenuate oxidative damage and to diminish the expression of inflammatory proteins and tissue damage in this experimental model.

Pse-T2, an Antimicrobial Peptide with High-Level, Broad-Spectrum Antimicrobial Potency and Skin Biocompatibility against Multidrug-Resistant Pseudomonas aeruginosa Infection.

Pseudin-2, isolated from the frog Pseudis paradoxa, exhibits potent antibacterial activity but also cytotoxicity. In an effort to develop clinically applicable antimicrobial peptides (AMPs), we designed pseudin-2 analogs with Lys substitutions, resulting in elevated amphipathic α-helical structure and cationicity. In addition, truncated analogs of pseudin-2 and Lys-substituted peptides were synthesized to produce linear 18-residue amphipathic α-helices, which were further investigated for their mechanism and functions. These truncated analogs exhibited higher antimicrobial activity and lower cytotoxicity than pseudin-2. In particular, Pse-T2 showed marked pore formation, permeabilization of the outer/inner bacterial membranes, and DNA binding. Fluorescence spectroscopy and scanning electron microscopy showed that Pse-T2 kills bacterial cells by disrupting membrane integrity. In vivo, wounds infected with multidrug-resistant (MDR) Pseudomonas aeruginosa healed significantly faster when treated with Pse-T2 than did untreated wounds or wounds treated with ciprofloxacin. Moreover, Pse-T2 facilitated infected-wound closure by reducing inflammation through suppression of interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor alpha (TNF-α). These data suggest that the small antimicrobial peptide Pse-T2 could be useful for future development of therapeutic agents effective against MDR bacterial strains.

Facing the facts on prophylactic antibiotics for facial fractures: 1 day or less.

BACKGROUND: To evaluate the role of initial prophylactic antibiotics on facial fractures, outcomes were compared between a short course (≤24 hours) of antibiotics to those who received an extended course (>24 hours). METHODS: Adults admitted (2010-2015) to a Level I trauma center intensive care unit with at least one facial bone fracture and major injuries isolated to the head and neck were included. Our primary analysis compared infectious complications of the head or neck (H/N infection) between patients given short or extended courses of antibiotic prophylaxis. Multivariate logistic regression and analysis of propensity score matched pairs were performed. RESULTS: A total of 403 patients were included, 85.6% had blunt injuries and 72.7% had their facial fracture managed nonoperatively. The H/N infection rate was 11.2%. Two hundred eighty patients received a short course of antibiotics and 123 patients received an extended course. Median Injury Severity Score was 14 in both groups (p = 0.78). Patients receiving an extended course of antibiotics had higher rates of H/N infection (20.3% vs. 7.1%, p < 0.001). Factors associated with development of H/N infection included younger age, penetrating injury, open fracture, upper face or mandible fracture, fractures in multiple facial thirds, vascular injury, hypertension, and extended antibiotic course. Multivariate logistic regression identified younger age (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.96-1.00; p = 0.02), multiple facial third fractures (OR, 4.9; 95% CI, 2.4-10.2; p < 0.001), and penetrating mechanism (OR, 3.1; 95% CI, 1.5-6.4; p = 0.003) as independent predictors of H/N infection, but not antibiotic duration. Propensity score-matched analysis found no differences in H/N infection between short and extended antibiotic courses (11.4% vs. 12.5%; p = 1.0). Subgroup analyses demonstrated no differences in H/N infection between short or extended antibiotic courses by injury pattern, mechanism, or treatment (operative or nonoperative). CONCLUSION: These results lead us to believe that we should limit antibiotics to 24 hours or less upon admission for facial fractures. LEVEL OF EVIDENCE: Therapeutic/care management, level IV.

In Vivo Efficacy of Histatin-1 in a Rabbit Animal Model.

Purpose/Aim: Corneal abrasions and nonhealing corneal epithelial defects are common conditions that cause pain and sometimes are slow to heal. Histatins, a family of histidine-rich peptides, have been implicated in oral and skin epithelial wound healing, and have been shown to be effective in vitro in human corneal epithelial cells. The objective of this study was to test the efficacy of histatin-1 on corneal epithelial wound healing in rabbits. MATERIALS & METHODS: Twenty-two (22) rabbits were separated into four treatment groups, each containing 3-7 rabbits. Treatments included three histatin-1 formulations (0.1 ug/ml. 1 ug/ml, and 10 ug/ml) and one inactive vehicle, one drop given three times per day. Eight (8) mm circular wounds were created using 0.5 ml of 20% ethyl alcohol in the right eye of each rabbit. A masked observer photographed each eye twice daily using slit-lamp biomicrophotography. Wound area was analyzed by using ImageJ. Statistical analysis was conducted using Graphpad Prism. RESULTS: Wound recovery was faster in animals given 0.1 ug/ml, 1 ug/ml, and 10 ug/ml when compared to the vehicle solution at 6, 24, and 30 hours after wound creation (p < 0.01). No adverse events were observed in any eyes. When analyzing area under the curve, % recovered area was higher overall in the 0.1 ug/ml (p < 0.01), 1 ug/ml (p < 0.01), and 10 ug/ml (p < 0.001) groups when compared to the vehicle solution. Hourly healing rate was also observed to be faster in the 0.1 ug/ml, 1 ug/ml, and 10 ug/ml groups (p < 0.001) at 24 hours postinjury suggesting an accelerated healing process as compared to the vehicle group. CONCLUSION: This study represents the first in vivo experiment evaluating and confirming the efficacy of topical histatin on the corneal epithelium wound healing. Further studiesare warranted to better understand the mechanism and safety of topical histatin-1 in corneal epithelial wound-healing and its potential role for human disease treatment.

Penehyclidine hydrochloride inhibits TLR4 signaling and inflammation, and attenuates blunt chest trauma and hemorrhagic shock-induced acute lung injury in rats.

Blunt chest trauma with hemorrhagic shock (THS) frequently induces pulmonary inflammation that leads to acute lung injury (ALI). Penehyclidine hydrochloride (PHC) possesses anti­inflammatory properties that may attenuate the systemic inflammatory response. The present study aimed to evaluate the molecular mechanism of PHC in modifying THS­induced ALI in rats. Rats underwent either THS or a sham procedure. At 6 h subsequent to blunt chest trauma, arterial blood was drawn for blood gas and pro­inflammatory factors analyses, and lung tissue samples were collected to examine pulmonary histopathological alterations, the wet/dry weight ratio, myeloperoxidase activity, and the protein expression levels of Toll-like receptor 4 (TLR4), phosphorylated (p­)p38 mitogen­activated protein kinase (MAPK), nuclear factor (NF)­κB and activator protein­1 (AP­1). THS caused significant reductions in heart rate and mean arterial blood pressure, and was associated with significant increases in tumor necrosis factor­α, interleukin (IL)­6, IL­1ß, p­p38MAPK, NF­κB and AP­1 activation, in addition to TLR4 expression, in the lung. PHC effectively attenuated THS­induced ALI, and inhibited TLR4 expression, reduced the activation of p­p38MAPK, NF­κB and AP­1, and downregulated the expression of pro­inflammatory mediators. In conclusion, the results of the present study demonstrated that PHC may exert an anti­inflammatory effect and attenuate THS­induced ALI by inhibiting the TLR4 signaling pathway. These preclinical findings may offer a novel therapeutic strategy to restrict TLR4 overactivation in ALI.