• Journal of Life Science
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• v.20 no.4
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• pp.474-480
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• 2010

Rutin, a group II phospholipase $A_2$ ($PLA_2$) inhibitor, was tested on interleukin-1 (IL-1) induced acute lung injury (ALI) in male Sprague-Dawley rats. Rutin did not alter the increased lung myeloperoxidase activity by IL-1. However, the number of neutrophils in bronchoalveolar lavage fluid (BALF) and IL-1 induced lung leak were decreased by rutin (p<0.001). Simultaneously, rutin decreased lung $PLA_2$ activity, which was increased by IL-1 (p<0.001). The reduction of neutrophilic respiratory burst by the inhibition of $PLA_2$ was confirmed by group II $PLA_2$ inhibitors such as rutin, manoalide and scalaradial. The increased level of cytokine-induced neutrophilic chemoattractant (CINC) in BALF by IL-1 was not affected by rutin. Ultrastructural changes of ALI and increased generation of free radicals in the lung by IL-1 were found, and rutin ameliorated these pathological findings. Taken together, rutin seems to be effective in decreasing IL-1 induced ALI through inhibition of group II $PLA_2$.

• Tuberculosis and Respiratory Diseases
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• v.74 no.3
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• pp.120-123
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• 2013

Inhalation of toxic gases can lead to pneumonitis. It has been known that methane gas intoxication causes loss of consciousness or asphyxia. There is, however, a paucity of information about acute pulmonary toxicity from methane gas inhalation. A 21-year-old man was presented with respiratory distress after an accidental exposure to methane gas for one minute. He came in with a drowsy mentality and hypoxemia. Mechanical ventilation was applied immediately. The patient's symptoms and chest radiographic findings were consistent with acute pneumonitis. He recovered spontaneously and was discharged after 5 days without other specific treatment. His pulmonary function test, 4 days after methane gas exposure, revealed a restrictive ventilatory defect. In conclusion, acute pulmonary injury can occur with a restrictive ventilator defect after a short exposure to methane gas. The lung injury was spontaneously resolved without any significant sequela.

• Journal of Trauma and Injury
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• v.34 no.3
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• pp.162-169
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• 2021

Purpose: For severe lung injuries or acute respiratory distress syndrome that occurs during critical care due to trauma, extracorporeal membrane oxygenation (ECMO) may be used as a salvage treatment. This study aimed to describe the experiences at a single center with the use of ECMO in trauma patients. Methods: We enrolled a total of 25 trauma patients who were treated with ECMO between January 2015 and December 2019 at a regional trauma center. We analyzed and compared patients' characteristics between survivors and non-survivors through a medical chart review. We also compared the characteristics of patients between direct and indirect lung injury groups. Results: The mean age of the 25 patients was 45.9±19.5 years, and 19 patients (76.0%) were male. The mean Injury Severity Score was 26.1±10.1. Ten patients (40.0%) had an Abbreviated Injury Scale (AIS) 3 score of 4, and six patients (24.0%) had an AIS 3 score of 5. There were 19 cases (76.6%) of direct lung injury. The mortality rate was 60.0% (n=15). Sixteen patients (64.0%) received a loading dose of heparin for the initiation of ECMO. There was no significant difference in heparin use between the survivors and non-survivors (70% in survivors vs. 60% in non-survivors, p=0.691). When comparing the direct and indirect lung injury groups, there were no significant differences in variables other than age and ECMO onset time. Conclusions: If more evidence is gathered, risk factors and indications will be identified and we expect that more trauma patients will receive appropriate treatment with ECMO.

• Journal of Trauma and Injury
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• v.18 no.1
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• pp.53-63
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• 2005

Purpose: This study was designed to determine if methylene blue inhibited the lipid peroxidation, the production of NO, and the gene expression of iNOS in acute lung injury induced by paraquat and if the inhibitory effect was dose dependent. Methods: Female Sprague-Dawley rats were divided into four groups: the control group, the group treated with paraquat only, the group treated with paraquat and a low dose of methylene blue (2 mg/kg), and the group treated with paraquat and a high dose of methylene blue (20 mg/kg). Methylene blue was administered via the jugular vein 1 h after paraquat administration, and animals were sacrificed 6 and 24 h after paraquat administration. Malondialdehyde (MDA) as lipid peroxidation, reduced glutathione (GSH) as an antioxidant defense, the plasma NO concentration, and the expression of iNOS mRNA in the lung tissue were measured Results: Lung MDA contents decreased, with no significant difference between the methylene-blue groups and the paraquat-only group. Lung GSH contents were significantly elevated at 24 h in the methylene-blue groups compared with the paraquat-only group. Plasma NO concentrations were significantly reduced at 6 and 24 h in the methylene-blue groups compared with the paraquat-only group. There was also a significant decrease in the plasma NO concentration at 6 h in the high-dose methylene-blue group compared with the low-dose methylene-blue group. The expression of iNOS mRNA in the lung tissue was slightly decreased in the methylene-blue groups. It was also markedly increased at 24 h in the paraquat-only group compared with the methylene-blue groups. The gene expression was relatively decreased in the high-dose methylene-blue group compared with the low-dose methylene-blue group. Conclusion: This study suggests that methylene blue has an inhibitory effect on the plasma NO concentration and the expression of iNOS mRNA in lung injury induced by paraquat. No inhibitory effect of methylene blue on lipid peroxidation or dose-dependent inhibitory effects were clearly shown.

• Tuberculosis and Respiratory Diseases
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• v.62 no.2
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• pp.105-112
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• 2007

Background: Oxidative stress may play an important role in the pathogenesis of endotoxin-induced acute lung injury (ALI). This study evaluated the therapeutic effect of ${\alpha}$-lipoic acid, a nonenzymatic antioxidant, in a rat model of lipopolysaccharide (LPS) induced ALI. Materials and Methods: ALI was induced in Sprague-Dawley rats by instilling LPS (E.coli, 3mg/Kg) into the trachea. The rats were classified into the control, control+${\alpha}$-lipoic acid, LPS, and LPS+${\alpha}$-lipoic acid groups.The lung lavage neutrophil count, cytokine-induced neutrophil chemoattractant (CINC), lung myeloperoxidase (MPO), and cytokine concentrations (TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and IL-10) were measured at 2 h and 6 h after LPS administration. Results: The total cell and neutrophil counts of the LPS+${\alpha}$-lipoic acid groups were significantly lower than the LPS groups. The protein concentration in the BAL fluid was similar in the LPS groups and LPS+${\alpha}$-lipoic acid groups. The TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 concentrations in the BAL fluid were not decreased by the ${\alpha}$-lipoic acid treatment in the LPS treated rats. Conclusions: Although ${\alpha}$-lipoic acid decreased the level of LPS-induced neutrophil infiltration into the lung, it could not attenuate the LPS-induced ALI at the dose administered in this study.

• Tuberculosis and Respiratory Diseases
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• v.63 no.6
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• pp.497-506
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• 2007

Background: The present investigation was performed in rats and isolated human neutrophils in order to confirm the presumptive role of the positive feedback loop of cytosolic phospholipase $A_2$ ($cPLA_2$) activation by plateletactivating factor (PAF). Methods: The possible formation of the positive feedback loop of the $cPLA_2$ activation and neutrophilic respiratory burst was investigated in vivo and in vitro by measurement of the parameters denoting acute lung injury. In addition, morphological examinations and electron microscopic cytochemistry were performed for the detection of free radicals in the lung. Results: Five hours after intratracheal instillation of PAF ($5{\mu}g/rat$), the lung leak index, lung myeloperoxidase (MPO) activity, the number of neutrophils and the concentration of cytokine-induced neutrophil chemoattractant (CINC) in bronchoalveolar lavage fluid were increased by PAF as compared with those of control rats. The NBT assay and cytochrome-c reduction assay revealed an increased neutrophilic respiratory burst in isolated human neutrophils following exposure to PAF. Lung and neutrophilic $cPLA_2$ activity were increased following PAF exposure and exposure to hydrogen peroxide increased $cPLA_2$ activity in the lung. Histologically, inflammatory findings of the lung were observed after PAF treatment. Remarkably, as determined by $CeCl_3$ cytochemical electron microscopy, increased production of hydrogen peroxide was identified in the lung after PAF treatment. Conclusion: PAF mediates acute oxidative lung injury by the activation of $cPLA_2$, which may provoke the generation of free radicals in neutrophils.

• Tuberculosis and Respiratory Diseases
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• v.70 no.1
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• pp.36-42
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• 2011

Background: Adaptive support ventilation (ASV), an automated closed-loop ventilation mode, adapts to the mechanical characteristics of the respiratory system by continuous measurement and adjustment of the respiratory parameters. The adequacy of ASV was evaluated in the patients with acute lung injury (ALI). Methods: A total of 36 patients (19 normal lungs and 17 ALIs) were enrolled. The patients' breathing patterns and respiratory mechanics parameters were recorded under the passive ventilation using the ASV mode. Results: The ALI patients showed lower tidal volumes and higher respiratory rates (RR) compared to patients with normal lungs ($7.1{\pm}0.9$ mL/kg vs. $8.6{\pm}1.3$ mL/kg IBW; $19.7{\pm}4.8$ b/min vs. $14.6{\pm}4.6$ b/min; p<0.05, respectively). The expiratory time constant (RCe) was lower in ALI patients than in those with normal lungs, and the expiratory time/RCe was maintained above 3 in both groups. In all patients, RR was correlated with RCe and peak inspiratory flow ($r_s$=-0.40; $r_s$=0.43; p<0.05, respectively). In ALI patients, significant correlations were found between RR and RCe ($r_s$=-0.76, p<0.01), peak inspiratory flow and RR ($r_s$=-0.53, p<0.05), and RCe and peak inspiratory flow ($r_s$=-0.53, p<0.05). Conclusion: ASV was found to operate adequately according to the respiratory mechanical characteristics in the ALI patients. Discrepancies with the ARDS Network recommendations, such as a somewhat higher tidal volume, have yet to be addressed in further studies.

• IMMUNE NETWORK
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• v.23 no.6
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• pp.48.1-48.21
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• 2023

Mesenchymal stromal/stem cells (MSCs) possess immunoregulatory properties and their regulatory functions represent a potential therapy for acute lung injury (ALI). However, uncertainties remain with respect to defining MSCs-derived immunomodulatory pathways. Therefore, this study aimed to investigate the mechanism underlying the enhanced effect of human recombinant bone morphogenic protein-2 (rhBMP-2) primed ES-MSCs (MSC^BMP2) in promoting Tregs in ALI mice. MSC were preconditioned with 100 ng/ml rhBMP-2 for 24 h, and then administrated to mice by intravenous injection after intratracheal injection of 1 mg/kg LPS. Treating MSCs with rhBMP-2 significantly increased cellular proliferation and migration, and cytokines array reveled that cytokines release by MSC^BMP2 were associated with migration and growth. MSC^BMP2 ameliorated LPS induced lung injury and reduced myeloperoxidase activity and permeability in mice exposed to LPS. Levels of inducible nitric oxide synthase were decreased while levels of total glutathione and superoxide dismutase activity were further increased via inhibition of phosphorylated STAT1 in ALI mice treated with MSC^BMP2. MSC^BMP2 treatment increased the protein level of IDO1, indicating an increase in Treg cells, and Foxp3⁺CD25⁺ Treg of CD4⁺ cells were further increased in ALI mice treated with MSC^BMP2. In co-culture assays with MSCs and RAW264.7 cells, the protein level of IDO1 was further induced in MSC^BMP2. Additionally, cytokine release of IL-10 was enhanced while both IL-6 and TNF-α were further inhibited. In conclusion, these findings suggest that MSC^BMP2 has therapeutic potential to reduce massive inflammation of respiratory diseases by promoting Treg cells.

• Archives of Pharmacal Research
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• v.29 no.4
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• pp.302-309
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• 2006

Lupus-like syndrome is characterized by multiple organ injuries including lungs and kidneys. Endotoxin induces a transiently intent systemic inflammatory response and indirectly transient acute lung injury in normal condition. However, whether endotoxin may trigger the persistent development of lung injury in chronic, inflammatory lupus-like syndrome compared with normal condition remains unclear. We examined the pulmonary vascular permeability and production of proinflammatory cytokines, such as TNF-${\alpha}$, IL-6, IL-10 and IFN-${\gamma}$, which play prominent roles in the pathogenesis of lupus-like tissue injury, 6 hand 72 h after i.p. lipopolysaccharide (LPS; endotoxin) injection in pristane-primed chronic inflammation ICR mice characterized by a lupus-like syndrome. These results demonstrated that levels of serum IL-6, IL-10 and IFN-${\gamma}$ and bronchoalveolar lavage (BAL) IL-6 and IFN-${\gamma}$ were remarkably increased 6 h in LPS-exposed pristane-primed mice compared with pristane-primed controls, while pulmonary vascular permeability and levels of serum and BAL TNF-${\alpha}$ were not. And levels of BAL TNF-${\alpha}$, IL-6 and IL-10 were significantly enhanced 72 h in LPS-exposed pristane-primed mice compared with pristane-primed controls. Also, LPS significantly induced the increased in vitro production of TNF-${\alpha}$, IL-6 and IL-10 by lung cells obtained from LPS-exposed pristane-primed mice compared with LPS-exposed normal mice. Our findings indicate that LPS may trigger persistent progression of lung injury through late overproduction of BAL TNF-${\alpha}$, IL-6, and IL-10 in lupuslike chronic inflammation syndrome compared with normal condition.

• Journal of Chest Surgery
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• v.12 no.4
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• pp.418-423
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• 1979

Chest injuries due to blunt trauma often result in severe derangements that lead to death. And we have to diagnose and treat the patients who have blunt chest trauma immediately and appropriately. A clinical analysis was made on 324 cases of chest injury due to blunt trauma experienced at department of Thoracic and Cardiovascular Surgery, College of Medicine, Kyung Hee University during 8-year period from 1972 to 1979. Of 324 patients of blunt chest injuries, there were 189 cases of rib fracture, 121 of hemothorax or/and pneumothorax, 108 of soft tissue injury of the chest wall only, 41 of lung contusion, 24 of flail chest, 13 of scapular fracture, 7 of diaphragmatic rupture and others. The majority of blunt chest injury patients were traffic accident victims and falls accounted for the next largest group of accidents. Chest injuries were frequently encountered in the age group between 3rd decade and 4th decade [60%] and 238 patients were male comparing to 86 of female [Male: Female = 3:1 ]. In the patients who have the more number of fractured ribs, the more incidence of intrathoracic injury and intraabdominal organ damage were found. The principal associated injuries were head injury on 58 cases, long bone fractures on 37, skull fractures on 12, pelvic fractures on 10, renal injuries on 6 and intraabdominal organ injuries on 5 patients. The principle of early treatment of chest injury due to blunt trauma were rapid reexpansion of the lung by closed thoracotomy which was indicated on 96 cases, but open thoractomy was necessary on 14 cases because massive bleeding, intrapleural hematoma and/or fibrothorax, or diaphragmatic laceration-On 15 cases who were young and have multiple rib fracture with severe dislocation delayed elective open reduction of the fractured ribs with wire was done on the purpose of preserving normal active life. The over all mortality was 2.8% [9 of 324 cases] due to head injury on 3 cases, massive bleeding on 2,wet lung syndrome, acute renal failure on 1 and septicemia on 1 patient.