• Tuberculosis and Respiratory Diseases
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• v.54 no.5
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• pp.532-541
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• 2003

Background : Phospholipase $A_2$ ($PLA_2$) has been known to be involved in the pathogenesis of acute lung injury (ALI) including ARDS. Since doxycycline has the property of inhibiting secretory group II $PLA_2$, the therapeutic effect of doxycycline hyclate was investigated for gut ischemia/reperfusion (I/R)-induced ALI in Sprague-Dawley rats. Methods : ALI was induced in Sprague-Dawley rats by clamping of the superior mesenteric artery for 60 min, followed by 120 min of reperfusion. To confirm the pathogenetic mechanisms of this ALI associated with neutrophilic oxidative stress, we measured bronchoalveolar lavage (BAL) protein content and lung MPO, and performed cyto-chemical electron microscopy for detection of free radicals, assay of $PLA_2$ activity and cytochrome-c reduction assay. Results : In gut I/R-induced ALI rats, protein leakage, pulmonary neutrophil accumulation, free radical production and lung $PLA_2$ activity were all increased. These effects were reversed by doxycycline hyclate. Conclusion : Doxycycline appears to be effective in ameliorating the gut I/R-induced ALI by inhibiting $PLA_2$, thereby decreasing the production of free radicals from neutrophils.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.3
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• pp.263-273
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• 1999

The role of phospholipase $A_2\;(PLA_2)$ in acute lung leak induced by intestinal ischemia was investigated in association with neutrophilic respiratory burst. To induce lung leak, we generated intestinal ischemia for 60 min prior to the 120 min reperfusion by clamping superior mesenteric artery in Sprague-Dawley rats. Acute lung leak was confirmed by the increased lung leak index and protein content in bronchoalveolar fluid. These changes were inhibited by mepacrine, the non-specific $PLA_2$ inhibitor. The lung myeloperoxidase (MPO) activity denoting the pulmonary recruitment of neutrophils was increased by intestinal I/R, but decreased by mepacrine. Simultaneously, the number of leukocytes in bronchoalveolar fluid was increased by intestinal ischemia/reperfusion (I/R) and decreased by mepacrine. Gamma glutamyl transferase activity, an index of oxidative stress in the lung, was increased after intestinal I/R but decreased by mepacrine, which implicates that $PLA_2$ increases oxidative stress caused by intestinal I/R. The $PLA_2$ activity was increased after intestinal I/R not only in the intestine but also in the lung. These changes were diminished by mepacrine. In the cytochemical electron microscopy to detect hydrogen peroxide, intestinal I/R increased the generation of the hydrogen peroxide in the lung as well as in the intestine. Expression of interleukin-1 (IL-1) in the lung was investigated through RT-PCR. The expression of IL-1 after intestinal I/R was enhanced, and again, the inhibition of $PLA_2$ suppressed the expression of IL-1 in the lung. Taken together, intestinal I/R seems to induce acute lung leak through the activation of $PLA_2$, the increase of IL-1 expression associated with increased oxidative stress by neutrophilic respiratory burst.

• Journal of Microbiology and Biotechnology
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• v.27 no.9
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• pp.1628-1638
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• 2017

Viola tianshanica Maxim, belonging to the Violaceae plant family, is traditionally used in Uighur medicine for treating pneumonia, headache, and fever. There is, however, a lack of basic understanding of its pharmacological activities. This study was designed to observe the effects of the ethanol extract (TSM) from Viola tianshanica Maxim on the inflammation response in acute lung injury (ALI) induced by LPS and the possible underlying mechanisms. We found that TSM (200 and 500 mg/kg) significantly decreased inflammatory cytokine production and the number of inflammatory cells, including macrophages and neutrophils, in bronchoalveolar lavage fluid. TSM also markedly inhibited the lung wet-to-dry ratio and alleviated pathological changes in lung tissues. In vitro, after TSM ($12.5-100{\mu}g/ml$) treatment to RAW 264.7 cells for 1 h, LPS ($1{\mu}g/ml$) was added and the cells were further incubated for 24 h. TSM dose-dependently inhibited the levels of proinflammatory cytokines, such as NO, $PGE_2$, $TNF-{\alpha}$, IL-6, and $IL-1{\beta}$, and remarkably decreased the protein and mRNA expression of $TNF-{\alpha}$ and IL-6 in LPS-stimulated RAW 264.7 cells. TSM also suppressed protein expression of $p-I{\kappa}Ba$ and p-ERK1/2 and blocked nuclear translocation of $NF-{\kappa}B$ p65. The results indicate that TSM exerts anti-inflammatory effects related with inhibition on $NF-{\kappa}B$ and MAPK (p-ERK1/2) signaling pathways. In conclusion, our data demonstrate that TSM might be a potential agent for the treatment of ALI.

• Tuberculosis and Respiratory Diseases
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• v.60 no.5
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• pp.564-570
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• 2006

Toxic gases and soot deposition as a consequence of smoke inhalation can cause direct injury to the upper and lower airways and even to the lung parenchyma. A delay in proper and prompt therapy can be detrimental to critically ill burn patients with an inhalation injury. Therefore, serial chest radiography is an important diagnostic tool for pulmonary complications during treatment. The radiographic findings of the chest include normal, consolidation, interstitial and alveolar infiltrates, peribronchial thickening, atelectasis, cardiogenic and non-cardiogenic pulmonary edema, and a pneumothorax as acute complications of smoke inhalation. In addition, bronchiectasis, bronchiolitis obliterans and pulmonary fibrosis can occur as late complications. We encountered a case of 44-year-old male who presented with acute lung injury after an inhalation injury. He required endotracheal intubation and mechanical ventilation due to respiratory failure. He was managed successfully with conservative treatment. Later, a cavitary lesion of the left upper lobe was observed on the chest radiography and computed tomography, which was complicated by massive hemoptysis during the follow-up. However, the cavitary lesion disappeared spontaneously without any clinical consequences.

• IMMUNE NETWORK
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• v.15 no.3
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• pp.142-149
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• 2015

Lung fibrosis is a life-threatening disease caused by overt or insidious inflammatory responses. However, the mechanism of tissue injury-induced inflammation and subsequent fibrogenesis remains unclear. Recently, we and other groups reported that Th17 responses play a role in amplification of the inflammatory phase in a murine model induced by bleomycin (BLM). Osteopontin (OPN) is a cytokine and extracellular-matrix-associated signaling molecule. However, whether tissue injury causes inflammation and consequent fibrosis through OPN should be determined. In this study, we observed that BLM-induced lung inflammation and subsequent fibrosis was ameliorated in OPNdeficient mice. OPN was expressed ubiquitously in the lung parenchymal and bone-marrow-derived components and OPN from both components contributed to pathogenesis following BLM intratracheal instillation. Th17 differentiation of $CD4^+$ ${\alpha}{\beta}$ T cells and IL-17-producing ${\gamma}{\delta}$ T cells was significantly reduced in OPN-deficient mice compared to WT mice. In addition, Th1 differentiation of $CD4^+$ ${\alpha}{\beta}$ T cells and the percentage of IFN-$\gamma$-producing ${\gamma}{\delta}$ T cells increased. T helper cell differentiation in vitro revealed that OPN was preferentially upregulated in $CD4^+$ T cells under Th17 differentiation conditions. OPN expressed in both parenchymal and bone marrow cell components and contributed to BLM-induced lung inflammation and fibrosis by affecting the ratio of pathogenic IL-17/protective IFN-$\gamma$ T cells.

• Herbal Formula Science
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• v.23 no.2
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• pp.171-187
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• 2015

Objective This study aimed to evaluate the effects of Sagan-tang (SGT) on COPD mouse model. Methods The study was carried out by two ways (in vitro, in vivo). In vitro RAW264.7 cells (mouse macrophage) were used and analysed by flow cytometry, ELISA, Western blot. In vivo LPS and CSS challenged mice were used and its BALF had been analysed by cytospin image, FACS, ELISA, lung tissue by real-time PCR. Results In vitro, SGT maintained 80-100% rate of viablilty on 10 ~ 500 ㎍/㎖ concentration. In ELISA analysis with RAW264.7 cells, SGT significantly decreased NO over 30 ㎍/㎖. In flow cytometry, SGT 100 ㎍/㎖ dosage group displayed a tendency for decrease ROS. In Western blot analysis, SGT 100 ㎍/㎖ dosage group decreased NF-κB. In ELISA analysis, SGT significantly decreased TNF-α, IL-6 over 200 ㎍/㎖. In vivo SGT 200 ㎎/㎏ dosage group, application of SGT significantly decreased increase of neutrophils, TNF-α, IL-6 in BALF, muc5AC, TGF-β, TNF-α, expression of mRNA in lung tissue and histological lung injury. Conclusion This Study suggests usability of SGT for COPD patients by controlling lung tissue injury.

• Journal of Trauma and Injury
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• v.21 no.2
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• pp.100-107
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• 2008

Purpose: A traumatic lung cyst (TLC) is a rare complication and is usually detected with a pulmonary contusion. This study attempted to identify the prognostic factors and the clinical characteristics for pulmonary contusion with TLCs. Methods: We retrospectively reviewed the medical records and chest CT findings of 71 TLC patients who visited our hospital from January 2006 to December 2007. Patients were assessed for any clinical characteristics. We evaluated significant differences between the survival and the death groups for patients with a traumatic lung cyst. Results: The male-to-female ratio of patients with TLCs was 54:17, and the mean age of the patients was $37.70{\pm}19.78years$ with 36.6% of the patients being under 30 years fo age. The cause of blunt thoracic trauma was mainly pedestrian traffic accidents (26.8%) and falls (25.4%). Associated conditions included pulmonary contusion in 68 patients (95.7%), hemopneumothorax in 63 patients (88.7%), and rib fracture in 52 patitents (73.2%). There was no consistent relationship between the number of TLCs and the pulmonary contusion score. The overall mortality rate of TLC patients was 26.8%. Death correlated with a need for ventilatory assistance, mean arterial pressure, worst mean arterial pressure in 24 hours, initial pH and base excess, worst pH and base excess in 24 hours, refractory shock, initial GCS score, and pulmonary contusion score. Conclusion: The presence of the aforementioned predictors indicate serious injury, which is the main determinant of the outcome for thoracic injuries with TLCs.

• Journal of Chest Surgery
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• v.50 no.5
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• pp.346-354
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• 2017

Background: Ventilator-associated pneumonia (VAP) is a common disease that may contribute to morbidity and mortality among trauma patients in the intensive care unit (ICU). This study evaluated the associations between trauma factors and the development of VAP in ventilated patients with multiple rib fractures. Methods: We retrospectively and consecutively evaluated 101 patients with multiple rib fractures who were ventilated and managed at our hospital between January 2010 and December 2015, analyzing the associations between VAP and trauma factors in these patients. Trauma factors included sternal fracture, flail chest, diaphragm injury, traumatic aortic dissection, combined cardiac injury, pulmonary contusion, pneumothorax, hemothorax, hemopneumothorax, abbreviated injury scale score, thoracic trauma severity score, and injury severity score. Results: Forty-six patients (45.5%) had at least 1 episode of VAP, 10 (21.7%) of whom died in the ICU. Of the 55 (54.5%) patients who did not have pneumonia, 9 (16.4%) died in the ICU. Using logistic regression analysis, we found that VAP was associated with severe lung contusion (odds ratio, 3.07; 95% confidence interval, 1.12 to 8.39; p=0.029). Conclusion: Severe pulmonary contusion (pulmonary lung contusion score 6-12) is an independent risk factor for VAP in ventilated trauma patients with multiple rib fractures.

• Journal of Chest Surgery
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• v.46 no.3
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• pp.197-201
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• 2013

Background: Most traumatic tracheobronchial injuries are fatal and result in death. Some milder cases are not life threatening and are often missed at the initial presentation. Tracheobronchial rupture is difficult to diagnose in the evaluation of severe multiple trauma patients. We reviewed the traumatic tracheobronchial injuries at Konyang University and Eulji University Hospital and analyzed the clinical results. Materials and Methods: From January 2001 to December 2011, 23 consecutive cases of traumatic tracheobronchial injury after blunt trauma were reviewed retrospectively. We divided them into two groups by the time to diagnosis: group I was defined as the patients who were diagnosed within 48 hours from trauma and group II was the patients who diagnosed 48 hours after trauma. We compared the clinical parameters of the two groups. Results: There was no difference in the age and gender between the two groups. The most common cause was traffic accidents (56.5%). The Injury Severity Score (ISS) was 19.6 in group I and 27.5 in group II (p=0.06), respectively. Although the difference in the ISS was not statistically significant, group II tended toward more severe injuries than group I. Computed tomography was performed in 22 cases and tracheobronchial injury was diagnosed in 5 in group I and 6 in group II, respectively (p=0.09). Eighteen patients underwent surgical treatment and all four cases of lung resection were exclusively performed in group II (p=0.03). There were two mortality cases, and the cause of death was shock and sepsis. Conclusion: We believe that close clinical observation with suspicion and rigorous bronchoscopic evaluation are necessary to perform diagnosis earlier and preserve lung parenchyma in tracheobronchial injuries from blunt trauma.

• Journal of Trauma and Injury
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• v.32 no.3
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• pp.136-142
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• 2019

Purpose: Near drowning refers to immediate survival after asphyxia due to submersion or immersion in water, which is a crucial public safety problem worldwide. Acute lung injury or acute respiratory distress syndrome (ARDS) is a common complication of near drowning. The purpose of this study was to investigate the feasibility and effectiveness of noninvasive nasal positive pressure ventilation (NINPPV). Methods: This retrospective study was conducted at a tertiary emergency department. NINPPV was administered for moderate ARDS caused by submersion or immersion in patients who were older than 18 years, from January 2015 to December 2018. We collected the demographic (age, sex, length of hospital stay, and outcome), laboratory (arterial blood gas, lactate, oxygen saturation, partial pressure of oxygen divided by the fraction of inspired oxygen, complete blood count, blood urea nitrogen, and creatinine), and clinical data (acute lung injury index and ventilator failure) of the patients. A statistical analysis was performed using Statistical Package for the Social Sciences version 20.0 for Windows. Results: NINPPV treatment was provided to 57 patients for near drowning, 45 of whom (78.9%) were successfully treated without complications; in 12 (21.1%), treatment was changed to invasive mechanical ventilation within 48 hours due to ARDS or acute kidney injury. NINPPV treatment was successful in 31 (75.6%) out of 41 sea-water near drowning patients. They were more difficult to treat with NINPPV compared with the fresh-water near drowning patients (p<0.05). Conclusions: NINPPV would be useful and feasible as the initial treatment of moderate ARDS caused by near drowning.