• Biomedical Science Letters
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• v.3 no.2
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• pp.139-150
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• 1997

In order to investigate the effect of aging and the $H_2O$$_2$ localization in association with histological, ultrastructural, and cytochemical studies in lung tissue after interleukin-1$\alpha$(IL-1) induced lung injury, an acute lung injury was induced by instillation of IL-1 into the trachea. Both of 4- and 20-months-old male rats, protein contents in IL-1 treated branchoalveolar lavage increased significantly compared to each control rats. Acute lung injury occured by oxidative stress because neutrophils accumulated in vascular lumen and formed the adhesion with endothelial cells. As these cause, tissue proteins were exuded and leukocytes migrated into the alveolar lumen. Neverthless in these lung injury $H_2O$$_2$ localization of IL-1 treated 20 months rats was not different compared to IL-1 treated 4 months rats. After all aging was not a factor to accelate IL-1 induced lung injury. Based on these results, it is suggested that neutrophil infilteration might be an important cause in acute lung injury, and aging is not a factor to change the acute lung injury by oxidative stress.

• Journal of Life Science
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• v.19 no.7
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• pp.878-885
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• 2009

Serum ferritin levels are elevated in subjects with acute lung injury (ALI), and abnormalities in plasma and lung iron chemistry have also been demonstrated in ALI and acute respiratory distress syndrome (ARDS). Stress-inducible heme oxygenase-1 (HO-1), as well as ferritin, had shown anti-inflammatory actions. Biomarkers for early detection in patients who are likely to develop ARDS would give several therapeutic chances to the patients. In order to verify the predictability in severe hemorrhage-induced ALI in rats, we measured serum ferritin and HO-1 concentrations before and after hemorrhage. Severe hemorrhages significantly increased the number of leukocytes in bronchoalveolar lavage (BAL) fluid and lung tissue myeloperoxidase activity. Both serum ferritin and HO-1 levels increased following hemorrhage, but ferritin levels were elevated earlier than HO-1. In BAL cell immunohistochemical studies, ferritin and HO-1 expressions increased after hemorrhage and localized in the cytoplasm of leukocytes. These findings suggest that inflammatory leukocytes in BAL fluid can secrete ferritin and HO-1, and serum ferritin levels might be more valid factor in predicting ARDS than HO-1 levels in hemorrhage-induced ALI.

• Tuberculosis and Respiratory Diseases
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• v.60 no.1
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• pp.49-56
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• 2006

배경 : 급성 폐손상은 폐내, 외의 원인질환들에 의해 폐포-모세혈관의 투과성이 증가하며, 폐부종에 의해 급성 저산소성 호흡곤란이 유발되는 증후군이다. 헤파린은 항응고작용 외에 자체적으로 항염증효과를 가지고 있으나, 염증성질환에 헤파린을 투여하면 출혈성 합병증이 발생하기 때문에 실제로 임상에서 이용하는데 제약이 있다. 하지만 헤파린에서 2-O와 3-O sulfate를 제거하면, 항응고 효과가 제거되고 항염증효과는 지니고 있는 비항응고성 헤파린 (nonanticoagulant heparin)으로 변화한다. 본 연구에서는 흰쥐에게 내독소 (LPS)를 투여하거나, 출혈성 쇼크를 일으켜서 유발된 급성폐손상에서 비항응고성 헤파린의 치료효과를 살펴보았다. 방법 : 각 군당 5 마리 이상의 흰쥐 (Balb/c mouse)를 이용하였다. 미정맥 (tail vein)을 통해 생리식염수 또는 비항응고성 헤파린 (50 mg/kg)을 투여한 직후에 내독소를 복강으로 투여하거나 (1 mg/kg), 심장천자를 통해 총 혈액의 1/3 정도로 제거하여 출혈성 쇼크를 유도하여 급성폐손상을 유발하였다. 내독소 투여 또는 출혈성 쇼크 유발 1 시간 후에 흰쥐를 희생시키고 폐를 적출하였고, 폐의 염증성 변화는 사이토카인 ($TNF-{\alpha}$, MIP-2, $IL-1{\beta}$)을 측정하여 살펴보았고, 폐손상의 정도는 myeloperoxidase (MPO) assay와 wet-to-dry weight ratio를 측정하여 알아보았다. 결 과 : 내독소를 투여한 흰쥐의 폐에서 대조군의 폐에 비해 사이토카인의 발현이 증가하고 ($TNF-{\alpha}$; $196.1{\pm}10.8$ vs $83.7{\pm}18.4pg/ml$, MIP-2; $3,000{\pm}725$ vs $187{\pm}26pg/ml$, $IL-1{\beta}$; $6,500{\pm}1167$ vs $266{\pm}25pg/ml$, p<0.05, respectively), 폐의 MPO 활성이 증가하였다 ($27.9{\pm}6.2$ vs $10.5{\pm}2.3U/g$ of lung protein, p<0.05). 출혈성 쇼크를 일으킨 흰쥐의 폐에서 대조군의 폐에 비해 사이토카인의 발현은 증가되지 않았으나, MPO 발현은 증가되었다 ($16.5{\pm}3.2$ vs $10.5{\pm}2.3U/g$ of lung protein, p<0.05). 내독소 투여 또는 출혈성 쇼크에 의해 급성폐손상이 유발된 흰쥐에서 생리적 식염수를 투여하거나 비항응고성 헤파린을 투여한 군 사이에 사이토카인의 발현이나 MPO 활성에 의미있는 차이는 관찰되지 않았다. 결론 : 이상의 결과로 비항응고성 헤파린은 내독소를 투여하거나 출혈성 쇼크를 일으키고 한 시간 뒤에 측정한 흰쥐의 급성폐손상에서 의미있는 치료효과를 보이지 않았다.

• Tuberculosis and Respiratory Diseases
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• v.60 no.4
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• pp.437-450
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• 2006

Background : Acute respiratory distress syndrome (ARDS) is characterized by severe inflammatory pulmonary edema of unknown pathogenesis. To investigate the pathogenesis of ARDS associated with neutrophilic oxidative stress, the role of phospholipase $A_2$ ($PLA_2$) was evaluated by the inhibition of calcium channel. Methods : In Sprague-Dawley rats, acute lung injury (ALI) was induced by the instillation of E.coli endotoxin (ETX) into the trachea. At the same time, diltiazem was given 60 min prior to tracheal instillation of ETX. Parameters of ALI such as lung and neutrophil $PLA_2$, lung myeloperoxidase (MPO), BAL neutrophils, protein, surfactant were measured. Production of free radicals from neutrophils was measured also. Morphological studies with light microscope and electron microscope were carried out and electron microscopic cytochemistry for detection of free radicals was performed also. Results : Diltiazem had decreased the ALI parameters effectively in ETX given rats and decreased the production of free radicals from neutrophils and lung tissues. Morphological studies denoted the protective effects of diltiazem. Conclusion : Diltiazem, a calcium channel blocker, was effective in amelioration of ALI by the suppression of neutrophilic oxidative stress mediated by $PLA_2$ activation.

• Tuberculosis and Respiratory Diseases
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• v.65 no.6
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• pp.464-470
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• 2008

Background: This study examined the role of neutrophilc oxidative stress in an $O_2-induced$ acute lung injury (ALI). Methods: For 48 h, experimental rats were exposed to pure oxygen (normobaric hyperoxia) in a plastic cage. Forty-eight hours after $O_2$ breathing, the rats were sacrificed and the parameters for ALI associated with neutrophilic oxidative stress were assessed Results: Normobaric pure oxygen induced ALI, which was quite similar to ARDS. The $O_2-induced$ neutrophilic oxidative stress was identified by confirming of the increase in lung myeloperoxidase, BAL neutrophils, malondialdehyde (MDA), cytosolic phospholipase $A_2$ ($cPLA_2$) activity in the lung, histological changes and BAL cytospin morphology. Conclusion: In part, ALI-caused by oxygen is affected by neutrophils especially by the generation of free radicals.

• Applied Microscopy
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• v.35 no.4
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• pp.84-90
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• 2005

Neutrophils that influx into the alveolar spaces from circulatory bloods play a important role in pathogenesis of acute lung injury. During the acute inflammatory phase, in order to investigate the acceleration of macrophage phagocytosis to the neutrophils is able to reduce the neutrophil-derived acute lung injury, endotoxemia was induced by insufflation of lipopolysaccharide intratracheally and organic germanium was injected intraperitoneally after endotoxin treatment. At 5 h after endotoxin treatment, lung weight and BAL protein concentration are significantly increased (p<0.001) compared to sham, and that was remarkedly decreased (p<0.001, p<0.01) by injection of germanium. In addition germanium treatment resulted to decreased the number of alveolar PMNs and to increase the percentage of engulfed neutrophils by alveolar macrophages. These observations indicate that organic germanium may have a role of reduction to neutrophil-derived acute lung injury in endotoxemia.

• 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.

• Journal of Yeungnam Medical Science
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• v.19 no.1
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• pp.55-62
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• 2002

Background: Interleukin-1(IL-1) and neutrophil appear to contribute to the pathogenesis of acute respiratory distress syndrome(ARDS). Elastase, as well as reactive oxygen species released from activated neutrophil, are thought to play pivotal roles in the experimental models of acute lung leak. This study investigated whether ICI 200,355, a synthetic elastase inhibitor, can attenuate acute lung injury induced by IL-1 in rats. Materials and Methods: We intratracheally instilled either saline or IL-1 with and without treatment of ICI 200,355 in rats. Lung lavage neutrophils, lung lavage cytokine-induced neutrophil chemoattractant(CINC) concentration, lung lavage protein concentration, lung myeloperoxidase(MPO) activity and lung leak index were measured at 5 hours of intratracheal treatment. Results: In rats given IL-1 intratracheally, lung lavage neutrophils, lung lavage CINC concentration, lung lavage protein concentration, lung MPO activity and lung leak index were higher. Intratracheal ICI 200,355 administration decreased lung lavage neutrophils, lung MFO activity and lung leak index, respectively, but did not decrease lung lavage CINC concentration. Conclusion: These results suggest that ICI 200,355 decreases lung inflammation and leak without decreasing lung lavage CINC concentration in rats given IL-1 intratracheally.

• Clinical and Experimental Pediatrics
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• v.50 no.5
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• pp.443-448
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• 2007

Purpose : To evaluate the potential prognostic value of the antithrombin-III (AT-III) level in the children with acute lung injury (ALI), we analyzed several early predictive factors of death including AT-III level at the onset of ALI and compared the relative risk of them for mortality. Methods : Over a 18-month period, a total of 198 children were admitted to our pediatric intensive care unit and 21 mechanically ventilated patients met ALI criteria, as defined by American-European consensus conference, i.e., bilateral pulmonary infiltrates and $PaO_2/FiO_2$ lower than 300 without left atrial hypertension. Demographic variables, hemodynamic and respiratory parameters, underlying diseases, as well as Pediatric Risk of Mortality-III (PRISM-III) scores and Lung Injury Score (LIS) at admission were collected. AT-III levels were measured within 3 hours after admission. These variables were compared between survivors and non-survivors and entered into a multiple logistic regression analysis to evaluate their independent prognostic roles. Results : The overall mortality rate was 38.1% (8/21). Non-survivors showed lower age, lower lung compliance, higher PEEP, higher oxygenation index (OI), lower arterial pH, lower $PaO_2/FiO_2$, higher PRISM-III score and LIS, and lower AT-III level. PRISM-III score, LIS, OI and decreased AT-III level (less than 70%) were independently associated with a risk of death and the odds ratio of decreased AT-III level for mortality is 2.75 (95% confidence interval; 1.28-4.12) Conclusion : These results suggest that the decreased level of AT-III is an important prognostic factor in children with ALI and the replacement of AT-III may be considered as an early therapeutic trial.

• Tuberculosis and Respiratory Diseases
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• v.42 no.5
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• pp.781-786
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• 1995

Transcatheter arterial chemoembolization(TACE) was performed in a 61 year old male patient with hepatocellular carcinoma with 10 cc of Lipiodol and 50 mg of doxorubicin. Three days later, he complained of dyspnea and dry cough. The arterial blood gas study revealed moderate hypoxemia and hypocarbia. The chest PA showed acute pulmonary edema with bilateral pleural effusion. To rule out the possibilities of acute respiratory failure caused by infection, pulmonary embolism or congestive heart failure, we performed several laboratory studies. The blood and sputum culture studies revealed negative results for bacterial growth. The echocardiogram was normal. The abdominal CT scan and MR imaging revealed no thrombus or mass lesion in the inferior vena cava. So we concluded pulmonary oil embolism induced by lipiodol as the cause of acute lung injury. Four weeks later, clinical symptoms and chest x-ray were markedly improved with conservative care. We report a case of acute lung injury after TACE with lipiodol and doxorubicin, with review of literatures.