The role of thoracic trauma in inflammatory responses, apoptosis and bacterial translocation following multiple traumas.

BACKGROUND: Blunt chest trauma and its complications are commonly encountered in emergency medicine. Herein, we used a rat model to investigate the role of thoracic trauma in inflammation, apoptosis and bacterial translocation following multiple traumas. METHODS: Ninety Wistar rats were divided equally into nine groups. Rats underwent a standardized blunt thoracic and/or head trauma and were sacrificed 24 or 48 hours after the trauma. Specimens from various organs and blood samples were collected and quantitatively cultured for aerobic organisms. Interleukins, TNF-α, and MCP-1 levels were assessed in the sera and markers of apoptosis were detected in the lungs. RESULTS: Levels of interleukins, TNF-α and MCP-1 in all of the groups undergoing trauma were significantly higher than those of the control group (p=0.001). Levels of apoptotic cells in the groups undergoing head and thoracic trauma (HTT) were significantly higher than those of the control group (p=0.009). Light microscopic evaluation indicated that damage in the HTT groups was significantly higher than that in the control group. The incidence of bacterial translocation was also significantly higher in the HTT groups (p=0.003). CONCLUSION: Multiple inflammatory mediators are activated in multiple traumas (including blunt thoracic trauma), which allow bacterial translocation and apoptotic processes to occur. Our results indicate that thoracic trauma plays a major role in post-traumatic bacterial translocation, inflammation, and apoptosis following multiple traumas.

Elastofibroma dorsi: Review of eight cases.

PURPOSE: Elastofibroma dorsi (ED) is a rare, benign soft tissue tumor arising from connective tissue and usually found in the subscapular region. We conducted this retrospective study to contribute to a better understanding of this tumor, the pathogenesis of which is still unclear. METHODS: We reviewed the medical records of eight patients treated for ED at our institution between 2003 and 2008. RESULTS: All patients were right-handed and all except one were female. The tumor was located on the right in two patients, on the left in one, and bilaterally in five. All patients underwent complete marginal resections. The resected tumors ranged in size from 5 cm to 12 cm. The only postoperative complication was seroma, observed in two patients. No recurrences have been observed in follow-up ranging from 15 days to 5 years. CONCLUSIONS: We could not establish a relationship between the side of the dominant hand and the tumor location. If this tumor becomes symptomatic, local excision is the best treatment; however, as malignant transformation has not been reported, follow-up is recommended for asymptomatic lesions.

Efficiency of lornoxicam in lung and trachea injury caused by peroxynitrite.

Peroxynitrite is involved in the pathogenesis of pulmonary diseases such as asthma, occupational pulmonary diseases and acute respiratory distress syndrome (ARDS) due to excessive production of nitric oxide or superoxide or both. Lornoxicam, a new oxicam derivative, is a potent anti-inflammatory agent. In this study, we evaluated the role of lornoxicam in a peroxynitrite-induced pulmonary and tracheal injury model by measuring myeloperoxidase (MPO) activity, malondialdehyde (MDA) and 3-nitrotyrosine (3-NT) levels in lung tissue and bronco-alveolar lavage fluid. The study protocol was based on three experimental groups as treatment (T), control (C) and peroxynitrite (P). Each group was subdivided into three subgroups as 2nd, 24th and 48th hour groups. P and T groups were injected intratracheal peroxynitrite. The T group received intraperitoneal lornoxicam before and 24h after peroxynitrite installation. Tissue and serum MDA, MPO values and tissue 3-NT value of the treatment and control groups were found significantly lower than the peroxynitrite group at the 2nd, 24th and 48th hours (p<0.05). Similarly, values obtained from bronco-alveolar lavage fluid examination in the control and treatment groups were significantly less than those in the peroxynitrite group (p<0.01). Therefore, Lornoxicam has been found to be effective in attenuating peroxynitrite induced pulmonary and tracheal injury in rats.

Effects of caffeic acid phenethyl ester on lipopolysaccharide-induced lung injury in rats.

Extracts of propolis, a natural beehive product, have been known for centuries to have a variety of beneficial medical properties, among which their anti-inflammatory effect is a major one. Caffeic acid phenethyl ester (CAPE), an active propolis component, has antimicrobial, anti-inflammatory, antioxidant, carcinostatic and immunomodulatory properties. In this study, we aimed to investigate the efficacy of CAPE in endotoxin-induced lung injury in rats. Lung injury was induced by a footpad injection of lipopolysaccharide (LPS). In the treatment group, 10 micromol kg(-1) CAPE was injected intraperitoneally immediately after LPS injection. At 24 h after LPS and/or CAPE injection, blood and lung tissue specimens were collected. MDA levels and MPO activity in serum and lung tissue, serum total antioxidant levels, lung tissue Na(+)/K(+) ATP-ase activity and histopathological evaluation were determined to assess the efficacy of CAPE treatment. CAPE was found to be efficient in reducing inflammation and lung tissue damage induced by LPS in rats.

Oleic acid-induced lung injury in rats and effects of caffeic acid phenethyl ester.

Caffeic acid phenethyl ester (CAPE) is a phenolic antioxidant and is an active anti-inflammatory component of honeybee propolis. The authors evaluated the effects of CAPE on oxidative stress and lung damage in an oleic acid (OA)-induced lung-injury model. Rats were divided into 5 groups as sham, OA, CAPE, pre-OA-CAPE, and post-OA-CAPE. Acute lung injury was induced by intravenous administration of 100 mg/kg of OA. Pre-OA-CAPE group received CAPE (10 micromol/kg. intravenously) 15 minutes before OA infusion and post-OA-CAPE group received CAPE 2 hours after OA administration. Malondialdehyde (MDA) level of plasma, bronchoalveolar lavage fluid (BALF), and lung tissue; myeloperoxidase activity of BALF and lung tissue; Na(+)-K(+) ATPase activity of lung tissue; and total protein content of BALF were measured. Light microscopic analyses of lung specimens were performed. The increased MDA levels in lung homogenates (47.98+/-13.75 nmol/mL), BALF (31.12+/-3.07 nmol/mL), and plasma (61.84+/-15.34 nmol/mL) decreased significantly to 24.33+/-3.09 nmol/mL (P = 0.000), 23.19+/-4.97 nmol/mL (P = 0.002), and 27.36+/-5.37 nmol/mL (P = 0.000), respectively, following CAPE administration in pre-OA-CAPE group. Another important finding was the restoration of the enzymatic activity of Na(+)-K(+) ATPase from a value of 203.89+/-32.18 nmol Pi/mg Protein/h in OA group, to a value of 302.17+/-51.90 nmol Pi/mg Protein/h (P = 0.012) in pre-OA-CAPE group with CAPE treatment. CAPE has been shown to have a clear attenuating effect on oxidative damage in experimental animal studies. However, further investigations are necessary to suggest CAPE as a treatment agent in critically ill patients with lung injury.

Rho-kinase (ROCK-1 and ROCK-2) upregulation in oleic acid-induced lung injury and its restoration by Y-27632.

The possible contribution of Rho/Rho-kinase signalling in oleic acid (100 mg kg-1, i.v., for 4 h)-induced lung injury was investigated in rats. Furthermore, the possible protective effect of the administration of a Rho-kinase inhibitor, (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexanecarboxamide dihydrochloride monohydrate (Y-27632, 0.5-5 mg kg-1, i.v., 15 min before the administration of oleic acid), was also examined. Western blot analysis as well as histopathological examination revealed that Rho-kinase (ROCK-1 and ROCK-2) was upregulated in lungs obtained from oleic acid-administrated rats. In addition, the markers of oxidative and nitrosative stress, i.e., malondialdehyde, myeloperoxidase, 3-nitro-L-tyrosine and nitrite/nitrate, in serum and lung tissue were also increased in the injury group. Treatment of rats with 5 mg kg-1 Y-27632 reversed the oleic acid-induced lung damage, which was demonstrated by histopathological assessment and confirmed in Western blot experiments: ROCK-blots were more intense in the oleic acid group than in control and Y-27632 treatment reversed ROCK upregulation. In addition, malondialdehyde, myeloperoxidase, 3-nitro-L-tyrosine and nitrite/nitrate were also normalized after the administration of Y-27632 (0.5 mg kg-1 and 5 mg kg-1). These findings suggest that ROCK-1 and ROCK-2 are involved in oleic acid-induced lung damage in rats, and that inhibition of this enzyme by Y-27632 may have a protective effect against such damage. Consequently, Rho kinase inhibitors may be potential therapeutic agents in the treatment of acute respiratory distress syndrome (ARDS).

Inhibition of poly(ADP-ribose) polymerase attenuates lung tissue damage after hind limb ischemia-reperfusion in rats.

The objective of this study was to investigate the effects of 3-aminobenzamide (3-AB) on tissue damage in lung after hind limb ischemia-reperfusion (I/R), by assessing blood biochemical assay and histopathological analysis. Thirty-five adult Wistar rats were divided into five groups. After application of anaesthesia both hind limbs were occluded with tourniquets. Following ischemia period for 60 min, the tourniquets were removed allowing reperfusion for 120 min. The IR group received 0.5 ml of saline while the IR+AB group received 3-AB (10 mgkg(-1) intraperitoneally). The IR+DMSO group was given 0.5 ml 10% DMSO 30 min before the removal of the tourniquets. The control group received 0.5 ml saline and the AB group received 0.5 ml 3-AB (10 mgkg(-1)) intraperitoneally. At the end of the reperfusion period, mid-line sternotomy was performed. Blood samples were taken with cardiac puncture. Bronchoalveolar lavage (BAL) of the left lung was performed with saline. Right lung was preserved for histopathological evaluation and biochemical examination. Lung tissue malondialdehyde (MDA) and 3-nitrotyrosine levels, myeloperoxidase and Na+/K+ ATP-ase activities, wet to dry weight ratios, and plasma and BAL fluid MDA levels were determined. Histopathological evaluation was performed, too. Hind limb IR caused significant increase in the lung tissue 3-NT to total tyrosine ratio (p = 0.014), wet to dry weight ratio (p = 0.000), MPO activity (p = 0.000), and MDA levels (p = 0.000). The animals treated with 3-AB showed a statistically significant decrease in these values (p < 0.05). Na+/K+ ATP-ase activity which was found to be decreased significantly with IR, returned to near normal levels with 3-AB treatment. Additionally, lung tissue injury in IR group characterized with moderate interstitial congestion and neutrophil infiltration, showed remarkable amelioration following 3-AB treatment. Our results strongly support the view that poly(ADP-ribose) polymerase (PARP) plays an important role in the inflammatory process in hind limb I/R-induced lung injury and as a PARP inhibitor, 3-AB seems to have a potential to treat this inflammatory injury.

The influence of iloprost on acute lung injury induced by hind limb ischemia-reperfusion in rats.

The local ischemia-reperfusion (I/R) process gains a systemic nature and affects distal organs. The remote effects of I/R are most frequently observed in the lungs and pulmonary damage may vary from acute lung injury with mild dysfunction to severe respiratory failure or the acute respiratory distress syndrome. In this hind limb I/R induced experimental lung injury model two groups of rats as IR and ILO were determined. Both groups underwent 60 min of ischemia and 120 min of reperfusion. While ILO group received iloprost in saline, IR group received only saline before reperfusion period intravenously. Serum myeloperoxidase (MPO) activity, malondialdehyde (MDA) levels and total antioxidant capacity (TAC) and lung tissue MPO activity, MDA levels and Na+-K+ ATPase activity were measured and light microscopic analyses of lung specimens were performed. The MPO activities in serum and lung homogenates were found to be significantly decreased in ILO group (P < or = 0.01). The MDA levels in lung homogenates were found to be significantly decreased in ILO group (P < or = 0.01), but the decreases were not significant in serum MDA levels (P=0.052). Serum TAC and lung tissue Na+-K+ ATPase activity levels were found to be increased in ILO group compared to IR group (P < or = 0.01). Lung histology showed marked improvement by iloprost compared to the IR group in this study. Iloprost has been found to be effective in attenuating ischemia reperfusion-induced remote organ damage, in this case, lung injury, in rats.

Effects of N-acetylcysteine on oxidant-antioxidant balance in oleic acid-induced lung injury.

The antioxidant and anti-inflammatory properties of N-acetylcysteine has been documented in many experimental lung injury models. Because intravenous injection of oleic acid induces histopathologic changes similar to those seen in human acute lung injury or acute respiratory distress syndrome, the authors evaluated the effects of N-acetylcysteine (NAC) on oxidative stress and lung damage in an oleic acid (OA)-induced lung injury model. Thirty-five rats were divided into 5 groups as sham, NAC, OA, pre-OA-NAC, and post-OA-NAC. Lung damage was induced by intravenous administration of oleic acid. Pre-OA-NACgroup received intravenous (IV) N-acetylcysteine 15 minutes before oleic acid infusion and post-OA-NAC group received IV N-acetylcysteine 2 hours after oleic acid infusion. In both of the N-acetylcysteine treatment groups, blood and tissue samples were collected 4 hours after oleic acid infusion, independent from the time of N-acetylcysteine infusion. In other groups, blood and tissue samples were collected 4 hours after ethanol, NAC, or OA infusions. Serum myeloperoxidase activity, total antioxidant capacity, malondialdehyde levels, and lung tissue Na+ - K+ ATPase activity were measured and light microscopic analyses of lung specimens were performed. The administration of N-acetylcysteine significantly restored Na+ - K+ ATPase activity and total antioxidant capacity levels and ameliorated lung architecture. N-acetylcysteine has been shown to have some attenuating effects in experimental animal studies. However, further investigations are necessary to suggest N-acetylcysteine as a treatment agent in critically ill patients with lung injury.

N-acetylcysteine inhibits peroxynitrite-mediated damage in oleic acid-induced lung injury.

Since oleic acid (OA) induces morphologic and cellular changes similar to those observed in human acute lung injury (ALI) and acute respiratory distress syndrome, it has become a widely used model to investigate the effects of several agents on pathogenesis of lung injury. The antioxidant and anti-inflammatory properties of N-acetylcysteine (NAC) has been documented in many lung injury models. In this study, we evaluated the role of NAC in an OA-induced lung injury model by measuring myeloperoxidase (MPO) activity, malondialdehyde (MDA) and 3-nitrotyrosine (3-NT) levels in lung tissue. Five groups labelled Sham, NAC, OA, Pre-OA-NAC and Post-OA-NAC were determined. ALI was induced by intravenous administration of OA. The pre-OA-NAC group received iv NAC 15 min before OA infusion and the post-OA-NAC group received iv NAC 2 h after OA infusion. In both of the NAC treatment groups' blood and tissue samples were collected 4 h after OA infusion, independent from the time of NAC infusion. The MPO activity, MDA and 3-NT levels in lung homogenates were found to be increased in OA group and the administration of NAC significantly reduced tissue MPO, MDA and 3-NT levels (p = 0.0001) Lung histopathology was also affected by NAC in this OA-induced experimental lung injury model.

The protective effect of N-acetylcysteine on apoptotic lung injury in cecal ligation and puncture-induced sepsis model.

Apoptotic loss of parenchymal cells may lead to organ dysfunctions in critically ill patients with septic states. As an antioxidant, the protective effects of N-acetylcysteine (NAC) are documented in many experimental and clinical studies. In this experimental study, we investigated the role of chronically used NAC in septic lung injury on a cecal ligation and puncture (CLP) model. To evaluate this, 30 male Wistar rats were randomly divided into four groups as sham (n = 7), CLP (n = 8), sham + NAC (n = 7) and CLP + NAC (n = 8) groups. NAC was administered 150 mg kg(-1) day through intramuscular route beginning 6 h after the operations and lasting for a period of 1 week. One week later, histopathology and epithelial apoptosis were assessed by hematoxylin-eosin and immunohistochemically by M30 and caspase 3 staining to demonstrate septic lung injury. Additionally, lung tissue myeloperoxidase (MPO) activity, malondialdehyde (MDA), and nitrite/nitrate levels were measured. The MPO activity and MDA levels in lung homogenates were found to be increased in CLP group and the administration of NAC prevented their increase significantly (P < 0.05). However, there were no significant differences among the groups regarding nitrite/nitrate levels. The number of apoptotic cells was significantly lower in CLP+NAC group than CLP group, and this finding was supported by M30 and caspase 3 expression in lung (P < 0.05). Lung histopathology was also protected by NAC in CLP-induced sepsis. In conclusion, the chronic use of NAC inhibited MPO activity and lipid peroxidation, which resulted in reduction of apoptosis in lung in this CLP model. Because lung tissue nitrite/nitrate levels did not change significantly, organs other than the lungs may be responsible for producing the increased nitric oxide during sepsis. The chronic use of NAC needs further investigation for its possible antiapoptotic potential in septic states besides its documented antioxidant and antiinflammatory effects.