• Journal of Chest Surgery
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• 제41권2호
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• pp.177-188
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• 2008

배경: 이 연구에서는 급성 폐 손상 백서 모델에 nitric oxide (NO)와 sphingosine 1-phosphate (S1P)를 투여한 후, 폐 미세구조의 변화를 생체 접촉 현미경 (intravital videomicroscopy) 으로 생체 내에서 직접 관찰하고 형태학적으로 분석하여, 급성 폐 손상 치료법으로서 이들의 효과를 평가하고자 하였다. 대상 및 방법: 백서 (Sprague Dawley rat) 35마리를 5군으로 나누었다: 생리 식염수를 흡입시킨 대조군 (n=7), 0.1 N HCl을 흡입시켜 폐 손상을 유도한 폐 손상 대조군 (ALI 군, n=7), 폐 손상을 유도하고 치료제를 투여한 치료군 (S1P군, n=7; NO 군, n=7; S1P+NO군, n=7). 폐포 유순도와 간질성 부종의 정도를 평가하기 위해, 폐 손상 유도 후 60 분과 120분에 측정 가능한 모든 폐포와 폐포간 벽의 두께를 생체 접촉 현미경으로 측정하였다. 폐포 유순도는 호흡 주기에 따른 폐포 직경 변화와 일회 호흡량의 변화에 따른 직경 변화로 평가하였다. 결과: 폐 손상 유도 120분 후에, ALI 군의 폐포 유순도가 대조 군 (호흡 주기에 따른 변화 : ALI군 1.9% vs 대조군 6.5%, p=0.03; 일회 호홉량에 따른 변화: ALI군 3.2% vs 대조군 9.1%, p=0.003)과 NO군(일회 호흡량에 따른 변화: ALI군 3.2% vs NO군 16.9%, p=0.001)에 비해 의미 있게 감소하였다. 폐 손상 유도 120 분 후에, NO군의 폐포간 벽의 두께가 ALI군에 비해 작은 경향을 보였다 (ALI 군 $15.2{\mu}m$ vs NO군 $12.3{\mu}m$, p=0.06). S1P 단독으로는 폐포 유순도와 간질성 부종에 유의한 영향을 미치지 않았다. 결론: 백서 폐 손상 모델을 생체 접촉 현미경으로 관찰한 결과, NO는 폐포 유순도를 개선하고 간질성 부종을 감소시켜 폐 손상 정도를 완화시키는 것으로 사료된다.

• Tuberculosis and Respiratory Diseases
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• 제45권4호
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• pp.888-895
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• 1998

Malaria is one of the most common infectious diseases in the world. Plasmodium falciparum, accounting for nearly all malaria mortality, kills an estimated 1 to 2 million persons yearly and has several features that make it deadlist of malarias. While cerebral malaria is the most common presentation of severe disease, acute lung injury associated with malaria is uncommon but serious and fatal complication. We report two cases of severe malaria with ARDS and multi-organ failure. All two patients traveled to foreign countries, Kenya, Papua New Guinea where choroquine-resistant malaria is distributed. The first case, which developed cerebral malaria, hypoglycemia, multi-organ failure, and ARDS, treated with quinine and mechanical ventilator, but expired due to oxygenation failure. Autopsy showed acute necrotizing infiltration, diffuse eosinophilic fibrinoid deposits along the alveolar space, and alveolar macrophage with malaria pigment The second case also developed multi-organ failure, followed by ARDS, and was treated with quinine, exchange transfusion, plasmapheresis, and mechanical ventilator. He recovered with residual restrictive lung change after treatment.

• Journal of Microbiology and Biotechnology
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• 제27권9호
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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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• 제71권5호
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• pp.368-372
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• 2011

Acute fibrinous and organizing pneumonia is a newly recognized pattern of acute lung injury. A 49-year-old female presented with a cough and worsening dyspnea on exertion. She had no history of smoking and no specific past medical history except exposure of home humidifier containing sterilizer. A chest computed tomography scan showed patchy consolidation with fibrosis in the right lower lobe and ill-defined centrilobular ground glass opacity in both lungs. The pathological findings were patchy areas of lung parenchyma with fibrin deposits in the alveolar ducts and alveoli, and fibrin balls with hemosiderin deposition in the alveolar spaces. The histological pattern of our case is differentiated from diffuse alveolar damage by the absence of hyaline membranes, and from eosinophilic pneumonia by the lack of eosinophils. In our case, the patient was treated with corticosteroid pulse therapy. However, the clinical course became aggravated and she died within two weeks.

• 동의생리병리학회지
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• 제24권5호
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• pp.843-847
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• 2010

Wikyung-Tang(WKT) is herbal medication used in abcess-causing respiratory disease. Previous in vitro study demonstrates that WKY presents anti-proliferative effects in A549 cells. Here we show that WKY protects mice against lipopolysaccharide(LPS)-induced acute lung injury (ALI). We pretreated mice orally with WKY(2.34 and 5.85 g/kg body weight) 1, 24 and 48 hours before intratracheal administration of LPS. For same condition, control group was pretaken orally distilled water before LPS administration. 24 hours after LPS intratracheal instillation, bronchoalveolar lavege fluids(BALF) was obtained to measure protein and proinflammatory cytokines(TNF-${\alpha}$, IL-$1{\beta}$, IL-6). Protein and proinflammatory cytokines in BALF of WKT treated groups were totally decreased. Statistically, Protein, TNF-${\alpha}$ and IL-$1{\beta}$ of high concentrate WKT treated group decreased significantly compared with control group. In conclusion, WKY had some anti-inflammatory effect in a clinically relevant model of ALI. these results indicated that WKY was effective in inhibiting ALI and might act as a potential therapeutic reagent for treating ALI in the future.

• Acute and Critical Care
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• 제33권4호
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• pp.206-215
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• 2018

Since the first successful lung transplantation in 1983, there have been many advances in the field. Nevertheless, the latest data from the International Society for Heart and Lung Transplantation revealed that the risk of death from transplantation is 9%. Various aspects of postoperative management, including mechanical ventilation, could affect intensive care unit stay, hospital stay, and immediate postoperative morbidity and mortality. Complications such as reperfusion injury, graft rejection, infection, and dehiscence of anastomosis increase fatal adverse side effects immediately after surgery. In this article, we review the possible immediate complications after lung transplantation and summarize current knowledge on prevention and treatment.

• 한국응급구조학회지
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• 제9권1호
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• pp.89-93
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• 2005

Penetrating chest trauma by stab injury may result in massive hemothorax from damage to single or multiple intrathoracic organs such as heart, aorta, internal mammary artery, intercostal artery or pulmonary parenchyme. Prognosis of massive hemothorax necessitating emergency thoracotomy is fatal especially so if there exists concomitant underlying compromise of cardiopulmonary function. A 56 year old man with destroyed left lung due to old pulmonary tuberculosis was stabbed in right parasternal lesion through third intercostal space. Intubation with cardiopulmonary resuscitation and closed thoracostomy were performed to resuscitate from cardiac asystole from hemorrhagic shock and acute respiratory distress. Midsternotomy was made to expose active bleeding foci in right mammary artery, subclavian vein, intercostal artery and anterior segment of right upper lung showing severe bullous change and pleural adhesion. Postoperative care included ventilator support, inotropic instillation and cautious, balance fluid therapy ; successful extubation was done on third postoperative day and patient was discharged on tenth postoperative day without any complication.

• Tuberculosis and Respiratory Diseases
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• 제39권1호
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• pp.42-54
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• 1992

연구배경 : 내독소 투여시 혈장과 폐의 림프내에 cyclooxygenase 대사물과 lipoxygenase 대사물이 모두 증가하고, cyclooxygenase 차단제로 초기의 혈역학적 변화가 완화되어 내독소에 의한 급성 폐손상의 기전에서 cyclooxygenase 대사물의 역할이 중요시 되고 있다. 그러나 cyclooxygenase 억제약물이 내독소 투여시 후기에 관찰되는 폐혈관 투과성 증가에 미치는 효과에 대해서는 논란이 있는 실정이고 cyclooxygenase 대사과정에 관여하는 peroxidase에 의해서 산소기가 생성된다고 알려져 있어 cyclooxygenase 대사물이 직접 폐손상을 일으키는지 또는 대사과정에서 생성되는 산소기를 통해 간접적으로 관여 하는지는 확실히 규명되어 있지 않은 상태이다. 저자들은 cyclooxygenase 대사물이 내독소에 의한 급성 폐손상의 기전에 직접적 또는 간접적으로 관여하는지를 알아보기 위해 본 연구를 시행하였다. 방법 : 총 8마리의 집돼지를 내독소 투여군(n=3)과 indomethacin 전처치 후 내독소를 투여한 군(n=5)으로 나누어 시간 경과에 따른 혈력학적 지표의 변화, 혈장내 산화 glutathione(GSSG) 및 기관지폐포세척액내의 알부민 농도를 측정하여 indomethacin 전처치가 내독소에 의한 급성 폐손상에 미치는 영향을 관찰하였다. 결과 : 1) 내독소 투여 후 phase 1(0-2 hr)과 phase 2(2-4.5 hr)에 걸쳐서 심박출양은 감소되고 평균 폐동맥압, 폐혈관저항, 폐포동맥간산소분압차는 증가되었으며 indomethacin 전처치로 두 phase의 변화가 모두 완화되었다. 2) phase 2에서 내독소에 의해 GSSG가 기저치에 비해 유의하게 증가했는데 indomethacin 전처치로는 완화되지 않았다. 3) 기관지폐포세척액내 알부민농도와 투과성지표는 내독소 투여군에 비해 indomethacin 전처치군에서 유의하게 낮았다. 결론 : 이상의 결과로 내독소에 의한 돼지의 급성 폐손상에는 cyclooxygenase 대사물이 초기와 후기 모두에 관여할 것으로 생각되고 indomethacin이 산소기에 의한 산화반응에 영향을 미치지 않는 것으로 보아 산소기를 통한 간접작용보다는 cyclooxygenase 대사물이 직접 병인론적 기전에 관여할 것으로 사료된다.

• Tuberculosis and Respiratory Diseases
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• 제44권6호
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• pp.1343-1352
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• 1997

연구배경 : 패혈증이나 이에 합병된 급성호흡곤란증후군 환자들은 고열을 동반하는 경우가 많다. 발열은 조직의 대사를 항진시키므로 조직내 산소공급에 제한이 초래되는 패혈증 환자들에서 발열이 동반되는 경우 열을 동반하지 않는 경우보다 중요기관의 산소공급이 상대적으로 저하될 가능성이 있다. 반면, 발열상태는 조직내 열충격단백질 (heat shock protein, HSP)의 생성을 유도하여 패혈증에 의한 비가역적인 손상으로부터 세포들을 보호함으로써 생체의 방어기전에 유려하게 작용할 수도 있어 패혈중 이에 합병된 급성 폐손상 환자들의 발열에 대한 임상적 의미는 아직 규명되어 있지않았다. 본 연구는 열을 전처치 하였거나 하지 않은 Sprague-Dawley rat의 기도에 TNF를 주입한 후 TNF에 의해 유도되는 급성 폐손상의 정도를 비교함으로써 열이 급성 폐손상에 미치는 효과를 관찰하고자 하였다. 대상 및 방법 : 급성 폐손상의 지표로는 백서의 우측폐내 $I^{125}$의 분당 측정량 대비 1mL의 혈중내 $I^{125}$의 분당 측정량의 비율로 정의한 단백누출지표와 백혈구의 조직내 침윤정도를 반영하는 myeloperoxidase(MPO)의 활성도를 측정하였다. 결과는 평균(${\pm}$ 표준오차)로 표기하였다. 결 과 : 백서의 기도에 생리식염수를 주입한 백서들은 열을 전처치 하였거나 하지 않은 경우 두 군사이의 단백 누출 지표는 각각 0.099(${\pm}0.024$) 및 0.123(${\pm}0.005$)로서 차이가 없었으며 MPO도 4.58(${\pm}0.79\;U/gm$) 및 7.32(${\pm}0.97\;U/gm$)로서 열을 전처치 할 경우 다소 감소되는 경향(P=0.064)를 보였으나 차이가 없었다. 백서의 기도에 TNF-$\alpha$을 주입한 치료군에서 열 전처치한 백서군은 단백누출지표 0.137(${\pm}0.012$) 및 MPO 7.01(${\pm}0.89\;U/gm$)로서 열 전처치 않은 백서군 단백누출지표 0.186(${\pm}0.015$) 및 MPO 14.11(${\pm}1.08\;U/gm$)에 비해 낮았으며(각 P<0.05) 정상군과는 차이가 없었다. MPO 활성도가 단백 증가되었다(r=0.564, P<0.005). 열 전처치 하지 않은 백서에 비해 열 전처치한 백서의 폐 조직내 HSP 72 단백질의 발현은 열 충격 후 18시간 및 23시간 뒤에도 증가되어 나타났다. 결 론 : 백서에 열을 전처치 할 경우 TNF-$\alpha$로 유도되는 급성 폐손상이 경감되므로 발열이 백서의 방어기전에 유리하게 작용한 것으로 사료되었다.

• International Journal of Stem Cells
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• 제16권2호
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• pp.191-201
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• 2023

Background and Objectives: O-cyclic phytosphingosine-1-phosphate (cP1P) is a synthetic chemical and has a structure like sphingosine-1-phosphate (S1P). S1P is known to promote cell migration, invasion, proliferation, and anti-apoptosis through hippocampal signals. However, S1P mediated cellular-, molecular mechanism is still remained in the lung. Acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) are characterized by excessive immune response, increased vascular permeability, alveolar-peritoneal barrier collapse, and edema. In this study, we determined whether cP1P primed human dermal derived mesenchymal stem cells (hdMSCs) ameliorate lung injury and its therapeutic pathway in ALI mice. Methods and Results: cP1P treatment significantly stimulated MSC migration and invasion ability. In cytokine array, secretion of vascular-related factors was increased in cP1P primed hdMSCs (hdMSC^cP1P), and cP1P treatment induced inhibition of Lats while increased phosphorylation of Yap. We next determined whether hdMSC^cP1P reduce inflammatory response in LPS exposed mice. hdMSC^cP1P further decreased infiltration of macrophage and neutrophil, and release of TNF-α, IL-1β, and IL-6 were reduced rather than naïve hdMSC treatment. In addition, phosphorylation of STAT1 and expression of iNOS were significantly decreased in the lungs of MSC^cP1P treated mice. Conclusions: Taken together, these data suggest that cP1P treatment enhances hdMSC migration in regulation of Hippo signaling and MSC^cP1P provide a therapeutic potential for ALI/ARDS treatment.