Caspase-2 Mediates Site-Specific Retinal Ganglion Cell Death After Blunt Ocular Injury.

Purpose: Ocular trauma is common in civilian and military populations. Among other injuries, closed globe blunt ocular trauma causes acute disruption of photoreceptor outer segments (commotio retinae) and retinal ganglion cell (RGC) death (traumatic optic neuropathy [TON]), both of which permanently impair vision. Caspase-2-dependent cell death is important and evidenced in models of RGC degeneration. We assessed the role of caspase-2 as a mediator of RGC and photoreceptor death in a rat blunt ocular trauma model. Methods: Bilateral ballistic closed globe blunt ocular trauma was induced in female Lister-hooded rats and caspase-2 cleavage and localization assessed by Western blotting and immunohistochemistry. Retinal caspase-2 was knocked down by intravitreal injection of caspase-2 small interfering RNA (siCASP2). In retinal sections, RGC survival was assessed by BRN3A-positive cell counts and photoreceptor survival by outer nuclear layer (ONL) thickness, respectively. Retinal function was assessed by electroretinography (ERG). Results: Raised levels of cleaved caspase-2 were detected in the retina at 5, 24, and 48 hours after injury and localized to RGC but not photoreceptors. Small interfering RNA-mediated caspase-2 knockdown neuroprotected RGC around but not in the center of the injury site. In addition, caspase-2 knockdown increased the amplitude of the ERG photopic negative response (PhNR) at 2 weeks after injury. However, siCASP2 was not protective for photoreceptors, suggesting that photoreceptor degeneration in this model is not mediated by caspase-2. Conclusions: Caspase-2 mediates death in a proportion of RGC but not photoreceptors at the site of blunt ocular trauma. Thus, intravitreally delivered siCASP2 is a possible therapeutic for the effective treatment of RGC death to prevent TON.

[Epidemiological, clinical and therapeutic aspects of blunt abdominal trauma in patients undergoing surgery at the General Hospital of National Reference of N'Djamena, Chad: about 49 cases]. / Aspects des traumatismes fermés de l'abdomen opérés à l'Hôpital Général de Référence Nationale de N'Djaména (HGRN), Tchad: à propos de 49 cas.

INTRODUCTION: Blunt abdominal traumas are common. METHODS: We retrospectively reviewed the medical records of 49 patients with blunt abdominal trauma who underwent surgery at the General Hospital of National Reference of N'Djamena, Chad over a period of 5 years. Epidemiological, clinical and therapeutic parameters of patients were studied. RESULTS: The study included 42 men and 7 women, mean age 21.3 years. The causes of blunt abdominal traumas were: road traffic accidents in 61.2% of cases; wall collapses (14.3%); assaults (8.2%). Blunt abdominal traumas were more frequent in August (14.28%) and October (16.32%). The waiting time for admission in hospital was 6-12h in 43% of cases. At discharge, wounded patients used private car in 85.7% of cases. Clinically, patients were often hemodynamically stable (55.1%). Medical imaging was dominated by direct radiography of the abdomen (57.1%). The most observed lesions were those located only in the small intestine (16.32%) or related to that of the bladder (8.16%) and spleen (2.04%). Laparotomy was negative in 6.12% of cases. Morbidity (12.2%) was dominated by abdominal wall abscess. Mortality rate was 6.1%. CONCLUSION: Road traffic accidents are the leading cause of blunt abdominal traumas. It is important to minimize delays in diagnosis, and treatment. Road safety measures should be implemented to prevent accidents.

Anti-aging pharmacology in cutaneous wound healing: effects of metformin, resveratrol, and rapamycin by local application.

Cutaneous wounds are among the most common soft tissue injuries and are particularly hard to heal in aging. Caloric restriction (CR) is well documented to extend longevity; pharmacologically, profound rejuvenative effects of CR mimetics have been uncovered, especially metformin (MET), resveratrol (RSV), and rapamycin (RAPA). However, locally applied impacts and functional differences of these agents on wound healing remain to be established. Here, we discovered that chronic topical administration of MET and RSV, but not RAPA, accelerated wound healing with improved epidermis, hair follicles, and collagen deposition in young rodents, and MET exerted more profound effects. Furthermore, locally applied MET and RSV improved vascularization of the wound beds, which were attributed to stimulation of adenosine monophosphate-activated protein kinase (AMPK) pathway, the key mediator of wound healing. Notably, in aged skin, AMPK pathway was inhibited, correlated with impaired vasculature and reduced healing ability. As therapeutic approaches, local treatments of MET and RSV prevented age-related AMPK suppression and angiogenic inhibition in wound beds. Moreover, in aged rats, rejuvenative effects of topically applied MET and RSV on cell viability of wound beds were confirmed, of which MET showed more prominent anti-aging effects. We further verified that only MET promoted wound healing and cutaneous integrity in aged skin. These findings clarified differential effects of CR-based anti-aging pharmacology in wound healing, identified critical angiogenic and rejuvenative mechanisms through AMPK pathway in both young and aged skin, and unraveled chronic local application of MET as the optimal and promising regenerative agent in treating cutaneous wound defects.

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.

Histone deactylase gene expression profiles are associated with outcomes in blunt trauma patients.

BACKGROUND: Treatment with histone deacetylase (HDAC) inhibitors, such as valproic acid, increases survival in animal models of trauma and sepsis. Valproic acid is a pan-inhibitor that blocks most of the known HDAC isoforms. Targeting individual HDAC isoforms may increase survival and reduce complications, but little is known of the natural history of HDAC gene expression following trauma. We hypothesized that distinct HDAC isoform gene expression patterns would be associated with differences in outcomes following trauma. METHODS: Twenty-eight-day longitudinal HDAC leukocyte gene expression profiles in 172 blunt trauma patients were extracted from the Inflammation and the Host Response to Injury (Glue Grant) data set. Outcome was classified as complicated (death or no recovery by Day 28, n = 51) or uncomplicated (n = 121). Mixed modeling was used to compare the HDAC expression trajectories between the groups, corrected for Injury Severity Score (ISS), base deficit, and volume of blood products transfused during the initial 12 hours following admission. Weighted gene correlation network analysis identified modules of genes with significant coexpression, and HDAC genes were mapped to these modules. Biologic function of these modules was investigated using the Gene Ontology database. RESULTS: Elevated longitudinal HDAC expression trajectories for HDAC1, HDAC3, HDAC6, and HDAC11 were associated with complicated outcomes. In contrast, suppressed expression of Sirtuin 3 (SIRT3) was associated with adverse outcome (p < 0.01). Weighted gene correlation network analysis identified significant coexpression of HDAC and SIRT genes with genes involved in ribosomal function and down-regulation of protein translation in response to stress (HDAC1), T-cell signaling, and T-cell selection (HDAC3) as well as coagulation and hemostasis (SIRT3). No coexpression of HDAC11 was identified. CONCLUSION: Expression trajectories of HDAC1, HDAC3, HDAC6, HDAC11, and SIRT3 correlate with outcomes following trauma and may potentially serve as biomarkers. They may also be promising targets for pharmacologic intervention. The effects of HDAC and SIRT gene expression in trauma may be mediated through pathways involved in ribosomal and T-cell function as well as coagulation and hemostasis. LEVEL OF EVIDENCE: Prognostic study, level III.

Is it possible to use transaminases for deciding on surgical or non-operative treatment for blunt liver trauma?

BACKGROUND: We aimed to research the relation of transaminase levels in blunt liver trauma (BLT) with the intensity of the trauma and the use of transaminase levels for deciding on surgical or non-operative treatment. METHODS: In all, 44 patients with BLT diagnosed by computerized tomography (CT) were involved in this retrospective study. By testing the correlation of the transaminase levels and the grade of liver injury with receiver operator characteristics (ROC), area under the curve (AUC) was calculated; besides, the sensitivity, specificity, and cut-off values of transaminases were calculated separately for the grades. Moreover, same method was repeated for the surgically and non-operatively treated patients. Cut-off value was assessed for surgical and non-operative treatments. The efficiency of transaminases in deciding non-operative treatment was compared with that of other methods using ROC test applied on focused abdominal sonography in trauma (FAST), hemodynamic instability, blood replacement rate, aspartate aminotransferase (AST), and alanine aminotransferase (ALT). RESULTS: It was observed that the AUC, sensitivity, and specificity increased correspondingly with the grade rise of transaminase levels in BLT. In the selection of non-operative treatment/surgery, following values have been confirmed: AUC for AST: 0.851 (sensitivity: 86%, specificity: 73%, cut-off value: 498 U/L), AUC for ALT: 0.880 (sensitivity: 86%, specificity: 81%, cut-off value: 498 U/L), AUC for replacement: 0.948 (sensitivity: 86%, specificity: 94%), AUC for hemodynamic instability: 0.902 (sensitivity: 86%, specificity: 94%), and AUC for FAST: 0.642 (sensitivity: 57%, specificity: 75%). CONCLUSIONS: It was found that in BLT, transaminases can predict the injury rating with higher accuracy as the grade rises, and they outrival FAST in terms of determining the need for laparotomy.

Caspase-9 mediates photoreceptor death after blunt ocular trauma.

PURPOSE: Ocular trauma is common in civilian and military populations. Commotio retinae involves acute disruption of photoreceptor outer segments after blunt ocular trauma, with subsequent photoreceptor apoptosis causing permanent visual impairment. The mechanisms of photoreceptor death in commotio retinae have not previously been described, although caspase-dependent death is important in other nontraumatic retinal degenerations. We assessed the role of caspase-9 as a mediator of photoreceptor death in a rat model of ballistic ocular trauma causing commotio retinae. METHODS: Bilateral commotio retinae was induced in rats by ballistic ocular trauma. Caspase-9 activity was assessed by immunohistochemistry, Western blotting, and bVAD-fmk active caspase capture. Caspase-9 was inhibited by unilateral intravitreal injection of highly specific X-linked inhibitor of apoptosis (IAP) baculoviral IAP repeat 3 (XBIR3) domain linked to the cell transduction peptide penetratin 1 (Pen-1) after ballistic injury, and the affected eyes were compared with control eyes treated with Pen-1 injection alone, and retinal function was assessed by electroretinogram a-wave amplitude and photoreceptor survival by outer nuclear layer thickness. RESULTS: Increased levels of cleaved caspase-9 were shown in photoreceptors 5 hours after injury, and catalytically active full-length caspase-9 was isolated from retinas. Photoreceptor death after commotio retinae was reduced by caspase-9 inhibition by using Pen-1-XBIR3, and electroretinographic measurements of photoreceptor function was preserved, providing structural and functional neuroprotection. CONCLUSIONS: The time course of caspase-9 activation and the neuroprotective effects of inhibition suggest that caspase-9 initiates cell death in a proportion of photoreceptors after blunt ocular trauma and that an intravitreally delivered biologic inhibitor may be an effective translational treatment strategy.

Utility of serum pancreatic enzyme levels in diagnosing blunt trauma to the pancreas: a prospective study with systematic review.

INTRODUCTION: Reliability of serum pancreatic enzyme levels in predicting pancreatic injuries has been a parameter of interest and the present recommendations on its utility are based primarily on anecdotal observations. The aim of this study was to evaluate the utility of serum pancreatic enzyme assessment in predicting blunt pancreatic injury with imaging and surgical correlation and compare our results with a systematic review of literature till date. METHODS: A prospective cohort study conducted over 4 years in a tertiary care referral centre with 164 consecutive patients who presented to the emergency department with a history of blunt abdominal trauma and had serum pancreatic enzyme assessment, USG and subsequent diagnostic CECT were analyzed. The CT findings and AAST grade of pancreatic injury, various intra-abdominal injuries and time elapsed since injury and other associated factors were correlated with serum pancreatic enzyme levels. For systematic review of literature MEDLINE database was searched between 1940 and 2012, also the related citations and bibliographies of relevant articles were analyzed and 40 articles were included for review. We compared our results with the systematic critique of literature till date to formulate recommendations. RESULTS: 33(21%) patients had pancreatic injury documented on CT and were graded according to AAST. Statistically significant elevated serum amylase levels were observed in patients with pancreatic and bowel injuries. However, elevated serum lipase was observed specifically in patients with pancreatic injury with or without bowel injury. Combined serum amylase and lipase showed 100% specificity, 85% sensitivity in predicting pancreatic injury. Elevated (n=28, 85%) vs. normal (n=5, 15%) serum amylase and lipase levels showed sole statistically significant association with time elapse since injury to admission, with a cutoff of 3h. CONCLUSIONS: Based on our results and the systematic review of the literature till date we conclude, persistently elevated or rising combined estimation of serum amylase and lipase levels are reliable indicators of pancreatic injury and is time dependent, nondiagnostic within 6h or less after trauma. In resource constrained countries where CT is not available everywhere it may support a clinical suspicion of pancreatic injury and can be reliable and cost-effective as a screening tool.

Liver trauma grading and biochemistry tests.

Among solid organ blunt traumas, the liver and spleen are mostly subject to injury. In addition, the liver is also commonly injured in penetrating traumas because of its size, location, and the ease of injury to the "Glisson Capsule". Several enzymes are known to be elevated following trauma. In our study, we evaluated the correlation between the levels of serum aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and gamma-glutamyl transpeptidase in 57 patients with blunt trauma to the liver and compared these values to the American Association for the Surgery of Trauma trauma grading system. Additionally, we compared the enzyme level elevations in these patients to the enzyme levels of 29 healthy subjects. As expected, we found significant elevations in enzyme levels of trauma patients compared to the control group. The calculated point estimates were not significantly different between grades 1 and 2 trauma. However, grade 3 trauma group showed a significant increase in enzyme levels.

The relationship of trauma severity and mortality with cardiac enzymes and cytokines at multiple trauma patients.

BACKGROUND: In this study, we aimed to determine the effects of trauma severity on cardiac involvement through evaluating the trauma severity score together with diagnostic tests in multiple trauma patients. A trauma score was determined using various trauma severity scales. METHODS: After obtaining the approval of the ethics committee of the faculty, this prospective study was performed through evaluating 100 multiple trauma patients, aged over 15 years, who applied to our Emergency Department (ED). After determining the trauma severity score using instruments such as the Injury Severity Score (ISS), Glasgow Coma Scale (GCS), and Revised Trauma Score (RTS), the cardiac condition was evaluated using biochemical and radiological diagnostic tests. RESULTS: During the study period, 100 patients were evaluated (78 male, 22 female; mean age: 33.2±15.4; range 15 to 70 years). It was determined that 92 (92%) were blunt trauma cases, and 77 (77%) of them were due to traffic accidents. The majority of cases showed electrocardiogram (ECG) abnormalities (63%) and sinus tachycardia (36%). Abnormal echocardiogram (ECHO) findings, mostly accompanied by ventricular defects (n=24), were determined in 31 of the cases. Nineteen cases with high trauma severity score resulted in death, and 14 of all deaths were secondary to traffic accidents. Trauma scores were found to show a significant difference between the two groups. CONCLUSION: The ISS trauma scale was determined to be the most effective in terms of indicating heart involvement in patients with multiple traumas. Close follow-up and cardiac monitoring should be applied to patients with high trauma severity scores considering possible cardiac rhythm changes and hemodynamic disturbances due to cardiac involvement.

Serum levels of ubiquitin C-terminal hydrolase distinguish mild traumatic brain injury from trauma controls and are elevated in mild and moderate traumatic brain injury patients with intracranial lesions and neurosurgical intervention.

BACKGROUND: This study compared early serum levels of ubiquitin C-terminal hydrolase (UCH-L1) from patients with mild and moderate traumatic brain injury (TBI) with uninjured and injured controls and examined their association with traumatic intracranial lesions on computed tomography (CT) scan (CT positive) and the need for neurosurgical intervention (NSI). METHODS: This prospective cohort study enrolled adult patients presenting to three tertiary care Level I trauma centers after blunt head trauma with loss of consciousness, amnesia, or disorientation and a Glasgow Coma Scale (GCS) score 9 to 15. Control groups included normal uninjured controls and nonhead injured trauma controls presenting to the emergency department with orthopedic injuries or motor vehicle crash without TBI. Blood samples were obtained in all trauma patients within 4 hours of injury and measured by enzyme-linked immunosorbent assay for UCH-L1 (ng/mL ± standard error of the mean). RESULTS: There were 295 patients enrolled, 96 TBI patients (86 with GCS score 13-15 and 10 with GCS score 9-12), and 199 controls (176 uninjured, 16 motor vehicle crash controls, and 7 orthopedic controls). The AUC for distinguishing TBI from uninjured controls was 0.87 (95% confidence interval [CI], 0.82-0.92) and for distinguishing those TBIs with GCS score 15 from controls was AUC 0.87 (95% CI, 0.81-0.93). Mean UCH-L1 levels in patients with CT negative versus CT positive were 0.620 (± 0.254) and 1.618 (± 0.474), respectively (p < 0.001), and the AUC was 0.73 (95% CI, 0.62-0.84). For patients without and with NSI, levels were 0.627 (0.218) versus 2.568 (0.854; p < 0.001), and the AUC was 0.85 (95% CI, 0.76-0.94). CONCLUSION: UCH-L1 is detectable in serum within an hour of injury and is associated with measures of injury severity including the GCS score, CT lesions, and NSI. Further study is required to validate these findings before clinical application. LEVEL OF EVIDENCE: II, prognostic study.

Progression of secondary injury after musculoskeletal trauma-a window of opportunity?

CONTEXT: Acute musculoskeletal-injury management largely focuses on inhibiting secondary injury, although the data describing secondary injury and the timeline for its progression are sparse. OBJECTIVE: To describe the timeline and early progression of secondary injury in skeletal muscle over the first 5 h after blunt trauma. DESIGN: A controlled laboratory study with 2 independent variables (injury status and postinjury time point) in a 2 × 21 factorial. SETTING: University research laboratory. SUBJECTS: 168 male Sprague Dawley rats (250 to 275 g). INTERVENTIONS: Uniform blunt-contusion injury was caused to the right triceps surae using a drop-weight method; the contralateral limb served as an uninjured control. Both triceps surae were excised and flash frozen at 21 intervals across 5 h postinjury (8 animals, each 15 min). MAIN OUTCOME MEASURES: Cytochrome-c oxidase activity via reduction of triphenyltetrazolium chloride (TTC) to triphenylformazan. RESULTS: There was an interaction effect (P = .041) between and main effects for both injury status (P < .0005) and postinjury time point (P = .038). In the first 30 min after injury, uninjured tissues did not differ from injured tissues, and both displayed TTC reduction rates in the vicinity of 7.1 ± 0.94 µg × mg-1 × h-1. Statistical differences between uninjured and injured tissues became evident starting at 30 min. TTC reduction for uninjured tissues did not change, but injured tissues declined in a roughly linear fashion across the entire 5-h period to 4.8 ± 1.04 µg × mg-1 × h-1. CONCLUSIONS: Cytochrome-c oxidase activity, an indicator of oxidative phosphorylation and mitochondrial viability, is diminished by events that follow muscle trauma. Loss of this enzymatic activity becomes statistically evident at 30 min postinjury and continues linearly for at least 5 h. This suggests that secondary injury is a slowly developing problem of more than 5 h duration. A window of opportunity for intervention may lie somewhere within the first 30 min after injury.

Hepatic enzymes have a role in the diagnosis of hepatic injury after blunt abdominal trauma.

INTRODUCTION: Delayed diagnosis of patients with severe liver injuries is associated with an adverse outcome. As computed tomographic (CT) scan is not always available in the management of blunt abdominal trauma worldwide, the present study was undertaken to determine the accuracy of selected haematological markers in predicting the presence of hepatic injury and its severity after blunt abdominal trauma. METHODS: A retrospective review of all patients with blunt abdominal trauma presented to our institution over a 3-year period was performed. Patients were excluded if they suffered penetrating injuries, died in the emergency department or if the required blood tests were not performed within 24h of the accident. The grading of the hepatic injury was verified using CT scans or surgical findings. RESULTS: Ninety-nine patients with blunt abdominal trauma had the required blood tests performed and were included in the study. The median injury severity score was 24 (range 4-75). Fifty-five patients had hepatic injuries, of which 47.3% were minor (Grades I and II) while 52.7% had major hepatic injuries (Grades III-V). There were no patients with Grade VI injuries. A raised ALT was strongly associated with presence of hepatic injuries (OR, 109.8; 95% CI, 25.81-466.9). This relation was also seen in patients with raised AST>2 times (OR, 21.33; 95% CI, 7.27-62.65). This difference was not seen in both bilirubin and ALP. ALT>2 times normal was associated with major hepatic injuries (OR, 7.15; 95% CI, 1.38-37.14; p=0.012) while patients with simultaneous raised AST>2 times and ALT>2 times had a stronger association for major hepatic injuries (OR, 8.44; 95% CI, 1.64-43.47). CONCLUSION: Abnormal transaminases levels are associated with hepatic injuries after blunt abdominal trauma. Patients with ALT and AST>2 times normal should be assumed to possess major hepatic trauma and managed accordingly. Patients with normal ALT, AST and LDH are unlikely to have major liver injuries.

Hepatic enzyme decline after pediatric blunt trauma: a tool for timing child abuse?

OBJECTIVES: Previous research in adult patients with blunt hepatic injuries has suggested a pattern of serum hepatic transaminase concentration decline. Evaluating this decline after pediatric blunt hepatic trauma could establish parameters for estimating the time of inflicted injuries. Deviation from a consistent transaminase resolution pattern could indicate a developing complication. METHODS: Retrospective review of pediatric patients with injuries including blunt liver trauma admitted to one of four urban level 1 trauma centers from 1990 to 2000. Cases were excluded for shock, death within 48 h, complications, or inability to determine injury time. Transaminase concentration decline was modeled by individual patients, by injury grade, and as a ratio with regard to injury time. RESULTS: One hundred and seventy-six patients met inclusion criteria. The rate of aspartate aminotransferase (AST) clearance changed significantly over time. Alanine aminotransferase (ALT) fell more slowly. Of the 118 patients who had multiple measurements of AST, for 112 (95%) the first concentration obtained was the highest. When ALT was greater than AST, the injury was older than 12h (97% specificity (95% CI, 95-99%), sensitivity 42% (95% CI, 33-50%)). Patients with enzymes that rose after 14 h post-injury were more likely to develop complications (RR=24, 95% CI 10-58). CONCLUSIONS: Hepatic transaminases rise rapidly after uncomplicated blunt liver injury, then fall predictably. Persistently stable or increasing concentrations may indicate complications. ALT>AST indicates subacute injury.

Expression of matrix metalloproteinases 2 and 9 in experimental corneal injury and fungal keratitis.

PURPOSE: Levels of matrix metalloproteinases (MMPs) can be modulated during corneal infection, but little is known about MMP profiles during fungal keratitis. The purpose of this study was to determine the effect of corneal trauma and immunosuppressive treatment on the expression kinetics of MMP-2 and MMP-9 during experimental keratomycosis. METHODS: Corneas of immunocompetent and cyclophosphamide-treated adult BALB/c mice were topically inoculated with 1 x 10 culturable units of Fusarium solani or mock-inoculated with or without superficial corneal scarification. Eyes were scored daily for disease severity and processed for zymography after 1.5 hours, 6 hours, 1 day, 4 days, or 8 days. Gelatinase activity was densitometrically quantitated and normalized to MMP-2 and MMP-9 controls. RESULTS: MMP-9 levels in nontraumatized eyes transiently increased at 6 hours after fungal exposure, but this increase was inhibited by cyclophosphamide treatment. Corneal injury significantly induced early MMP-9 expression that returned to baseline levels within 4 days. Cyclophosphamide pretreatment reduced and delayed MMP-9 after scarification. Fusarium exposure dampened the MMP-9 response to corneal trauma in immunocompetent and cyclophosphamide-treated animals. Ocular levels of MMP-2 were not affected by scarification, fungal exposure, or immunosuppressive treatment. CONCLUSIONS: Ocular MMP-9 levels, but not MMP-2 levels, increased soon after corneal injury. A similar, although muted, MMP-9 response occurs during early filamentous fungal keratitis, with a kinetic profile similar to corneal disease progression. The early stage of ulcerative keratitis may involve selective regulation of corneal matrix metalloproteinases, suggesting an initial opportunity for therapeutic intervention.

[The effect of carnosine on inflammatory processes during contusion of the eyeball].

The effect of dipeptide carnosine on proteolytic processes accompanying inflammation was investigated in lacrimal fluid of patients with eyeball contusion. Eye drops containing 5% carnosine in combination with traditional treatment reduced elastase-like activity in lacrimal fluid and increased effectiveness of therapy.

Extracellular signal-regulated kinase mitogen-activated protein kinase activation in the dorsal root ganglion (DRG) and spinal cord after DRG injury in rats.

STUDY DESIGN: We investigated the extracellular signal-regulated kinase (ERK) activation by immunohistochemically detecting phosphorylated ERK (pERK) in the dorsal root ganglion (DRG) and spinal cord. OBJECTIVE: To clarify the ERK activation in the rat nervous system following DRG injury. SUMMARY OF BACKGROUND DATA: Radicular pain is known to be associated with DRG injury caused by intervertebral disc herniation. ERK is activated by phosphorylation in the DRG and spinal cord by noxious stimuli, which are related to pain hypersensitivity. METHODS: From 2 minutes to 24 hours after the left L4 DRG crush injury, L4 DRGs and spinal cords were resected to prepare serial sections, which were investigated immunohistochemically. RESULTS: In the DRG, ERK activation was detected in neurons and satellite cells at 2 minutes; the former was maintained at increased levels for 20 minutes, and the latter for 4 hours. At 30 minutes, pERK immunoreactivity was observed in Schwann cells, which continued for up to 24 hours. In the spinal cord, pERK-positive neurons were detected at 2 minutes, and the pERK levels were maintained at increased levels for 20 minutes. CONCLUSIONS: Profiles of pERK induction in neurons after DRG injury were similar between the DRG and spinal cord, whereas pERK induction in the satellite cells was more long lasting. The pERK induction in Schwann cells in the DRG was late onset and the most long lasting.

Mitogen-activated protein kinases phosphorylation in posttraumatic selective vulnerability in rats.

Mitogenic stimulation of the Mitogen-activated protein kinase (MAPK) pathway modulates the activity of many transcriptional factors leading to biological responses. Of these, three MAPK cascades are well characterized as extracellular signal-regulated protein kinase (ERK), c-Jun NH(2)-terminal kinase (JNK), and p38 pathways. The aim of this study was to investigate the topographic distribution and the role of activated MAPK pathways after fluid percussion injury (FPI) in rats. In the present results, FPI significantly induced ERK- and JNK-phosphorylation, but not p38-phosphorylation in the cortex and hippocampus at the injury site. The immunoreactivity for phospho-ERK was localized in the superficial neuronal layers, dentate hilar neurons, and the damaged CA3 neurons after 30 mins of FPI. Double immunostaining showed that phospho-ERK was prominent in astrocytes 6 hrs after TBI. The current results suggest that MAPK pathways are involved in signal transduction after FPI.

Liver enzymes as predictors of liver damage due to blunt abdominal trauma in children.

BACKGROUND: Blunt abdominal trauma in children can result in injury to the liver. In hemodynamically stable patients, initial evaluation of liver transaminase levels may be useful in determining the need for computed tomography (CT). METHODS: We reviewed the medical records of 44 hemodynamically stable children who had abdominal CT and who also had liver enzyme determinations as the initial workup. RESULTS: Liver enzymes were found to be elevated in all but one patient with CT confirmed hepatic injury. The sensitivity and specificity of elevated liver enzyme levels were 92.9% and 100%, respectively, for predicting liver injury. CONCLUSION: When hemodynamically stable pediatric patients with blunt abdominal trauma have AST levels >400 and/or ALT levels >250 IU/L, abdominal CT is indicated. Children in this study with serum transaminase levels below these values were at decreased risk of liver injury.