• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.22 no.4
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• pp.301-308
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• 2012

Objectives: To evaluate the pulmonary toxicity of 2 Korea asbestos(chrysotile, anthophyllite), Sprague-Dawely rats were exposed to 2 mg domestic asbestos by intratracheal instillation(IT). Methods: Lung function of rats was analyzed by pressure transducer(MAX1320, Buxco Electronics, USA). The effects of 2 mg asbestos(chrysotile ; $8,814,244{\times}10^{6}$ fibers/mg, average diameter 0.08 ${\mu}m$, average length 4.39 ${\mu}m$, anthophyllite ; $5,182{\times}10^{6}$ fibers/mg, average diameter 0.95 ${\mu}m$, average length 7.29 ${\mu}m$) on pulmonary function and pathological changes were evaluated at after a single IT. Lung function and histopathological evaluation were assessed in 5 animals from each group at each time point. Results: Due to differences in fiber numbers, chrysotile induce marked lung pathology and lung function change than anthophyllite at the same mass dose. Chrysotile showed notable thickening of interstitial areas surrounding the alveolar ducts and terminal bronchioles. Conclusions: On a mass dose basis, chrysotile that have 1,700 times numbers of fibers per unit weight than anthophyllite produced a greater persistent lung injury than anthophllite for at least 4 weeks after exposure.

• Journal of Chest Surgery
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• v.32 no.7
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• pp.637-647
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• 1999

Background: Ischemia-reperfusion injury is one of the major contributing causes of early graft failure in lung transplantation. It has been suggested that triiodothyronine (T3) may ameliorate ischemia-reperfusion injury to various organs in vivo and in vitro. Predicting its beneficial effect for ischemic lung injury, we set out to demonstrate it by administering T3 into the in situ canine ischemia-reperfusion model. Material and Method: Sixteen adult mongrel dogs were randomly allocated into group A and B. T3 $(3.6\mug/kg)$ was administered before the initiation of single lung ischemia in group B, whereas the same amount of saline was administered in group A. Ischemia was induced in the left lung by clamping the left hilum for 100 minutes. After reperfusion, various hemodynamic parameters and blood gases were analyzed for 4 hours while intermittently clamping the right hilum in order to allow observation of the injured left lung function. Result: Arterial oxygen partial pressure $(PaO_2)$ decreased 30 minutes after reperfusion and recovered gradually thereafter in both groups. In group B the decrease of $PaO_2$ was less marked than in group A. The recovery of $PaO_2$ was faster in group B than in group A. The differences between the two groups were statistically significant from 30 minutes after reperfusion $(125\pm34$ mmHg and $252\pm44$ mmHg, p<0.05) until the end of the experiment $(178\pm42$mmHg and $330\pm37$ mmHg, p<0.05). The differences in the arterial carbon dioxide pressure, airway pressure and lung compliance showed no statistical significance. The malondialdehyde (MDA) level, measured from the tissue obtained 240 minutes after reperfusion, was lower in group B $(0.40\pm0.04\mu$M) than in group A $(0.53\pm0.05\mu$M, p<0.05). The ATP level of group B $(0.69\pm0.07\mu$M/g) was significantly higher than that of group A $(0.48\pm0.07\mu$M/g, p<0.05). The microscopic exami nation revealed varying degrees of injury such as perivascular neutrophil infiltration, capillary hemorrhage and interstitial congestion. There were no differences in the microscopic findings between the two groups. CONCLUSION T3 has beneficial effects on the ischemic canine lung injury including preservation of oxygenation capacity, less production of lipid peroxidation products and a higher level of tissue ATP. These results suggest that T3 is effective in pulmonary allograft preservation.

• Journal of Chest Surgery
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• v.22 no.6
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• pp.914-920
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• 1989

Bleomycin and cyclophosphamide are widely used and effective anti-cancer agents for treatment of various forms of cancer. Bleomycin has no myelotoxicity, but because of potential risk of pulmonary complications including interstitial pneumonitis and idiopathic interstitial pulmonary fibrosis, it has been limited in use. Some investigator has also suggested that cyclophosphamide can induce pulmonary toxicity like bleomycin. Recently, The combination chemotherapy including bleomycin and cyclophosphamide has been adopted effectively in some types of cancer. But there are no available literatures for synergistic effect of pulmonary toxicity in combination chemotherapy including these two drugs. We tried this study to observe synergism of pulmonary toxicity using these two drugs in rats. The animals were divided into five groups: group 1 received intra-peritoneal injection of saline, group 2-a received only bleomycin 0.1 mg [0.4 mg/kg] by intra-peritoneal injection twice a week, group 2-b received only bleomycin 0.5 mg [2 mg/kg] by intra-peritoneal injection twice a week, group 3-a received bleomycin 0.1 mg [0.4 mg/kg] twice a week +cyclophosphamide 5 mg [20 mg/kg] two weeks interval by intra-peritoneal injection, group 3-b received bleomycin 0.5 mg [2 mg/kg] twice a week + cyclophosphamide 5 mg[20 mg/kg] two weeks interval by intra-peritoneal injection. The animals were sacrificed at 2 and 4 weeks later. Lung tissues were obtained and observed by light microscope. The results are as follows: 1. The pathologic findings of group 1 were normal without change. 2. There was no difference between group 2-a and group 3-a at 2 weeks later, group 3-a, however, revealed more severe change in lung tissue at 4 weeks later compared with group 2-a. 3. In group 3-b there was more severe pulmonary injury compared with group 2-b at 2 and 4 weeks later. We conclude that the combined administration of bleomycin and cyclophosphamide induce more severe pulmonary toxic effect than bleomycin administration alone and the combination chemotherapy including these two drugs will be require special attention to selection of the dose of each drug.

• 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.

• Tuberculosis and Respiratory Diseases
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• v.51 no.2
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• pp.161-165
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• 2001

Acute bilateral reexpansion pulmonary edema after pleurocentesis is a rare complication. In one case, bilateral reexpansion pulmonary edema after unilateral pleurocentensis in sarcoma was reported. Various hypotheses regarding the mechanism of reexpansion pulmonary edema include increased capillary permeability due to hypoxic injury, decreased surfactant production, altered pulmonary perfusion and mechanical stretching of the membranes. Ragozzino et al suggested that the mechanism leading to unilateral reexpansion pulmonary edema involves the opposite lung when there is significant contralateral lung compression. Here we report a case of bilateral reexpansion pulmonary edema and acute respiratory distress syndrome after a unilateral pleurocentesis of a large pleural effusion with contralateral lung compression and increased interstitial lung marking underlying chronic liver disease.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.4
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• pp.267-274
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• 2013

A beneficial radioprotective agent has been used to treat the radiation-induced lung injury. This study was performed to investigate whether curcumin, which is known to have anti-inflammatory and antioxidant properties, could ameliorate radiation-induced pulmonary inflammation and fibrosis in irradiated lungs. Rats were given daily doses of intragastric curcumin (200 mg/kg) prior to a single irradiation and for 8 weeks after radiation. Histopathologic findings demonstrated that macrophage accumulation, interstitial edema, alveolar septal thickness, perivascular fibrosis, and collapse in radiation-treated lungs were inhibited by curcumin administration. Radiation-induced transforming growth factor-${\beta}1$ (TGF-${\beta}1$), connective tissue growth factor (CTGF) expression, and collagen accumulation were also inhibited by curcumin. Moreover, western blot analysis revealed that curcumin lowered radiation-induced increases of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), TNF receptor 1 (TNFR1), and cyclooxygenase-2 (COX-2). Curcumin also inhibited the nuclear translocation of nuclear factor-${\kappa}B$ (NF-${\kappa}B$) p65 in radiation-treated lungs. These results indicate that long-term curcumin administration may reduce lung inflammation and fibrosis caused by radiation treatment.

• Radiation Oncology Journal
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• v.15 no.1
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• pp.37-47
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• 1997

Purpose : To investigate ultrastructural changes of the mouse lung induced by whole lung gamma irradiation and to evaluate the effect of prophylactic administration of steroid against acute lung injury. Materials and Methods :. One hundred and twenty ICR mice were used and whole lung was irradiated with telecobalt machine. Whole lung doses were 8 and 12Gy, and 10mg of methyl prednisolone was administrated intraperitoneally for two and four weeks. At the end of the observation period, mice were sacrificed by cervical dislocation. The lungs were removed and fixed inflated. Histopathological examination of acute radiation injuries were Performed by light microscopic and transmission electron microscopic examination. Results : Control group with BGy is characterized by damage to the type I Pneumocyte and the endothelial cell of the capillary. edema of alveolar wall and interstitium. and fibroblast proliferation. Control group with 120y is characterized by more severe degree of type 1 pneumocyte damage and more prominant inflammatory cell infiltration. Destructed cell debris within the alveolar space were also noted After steroid administration, 8Gy experimental group showed decreased degree of inflammatory reactions but fibroblast proliferation and basal lamina damages were unchanged. Experimental group with 12Gy showed lesser degree of inflammatory reactions similar to changes of 8Gy experimental group. Conclusion : These studies suggest that the degree of interstitial edema and inflammatory changes were related to radiation dose but Proliferation of the fibroblast and structural changes of basal lamina were not related to radialion dose. Experimental administration of steroid for 2 to 4 weeks after whole lung irradiation suggest that steroid can suppress alveolar and endothelial damages induced by whole lung irradiation but Proliferation of the fibroblast and structural changes of basal lamina were not related to administration of steroid.

• Tuberculosis and Respiratory Diseases
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• v.48 no.4
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• pp.478-486
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• 2000

Background : In acute lung injury, alveolar macrophages play a pivotal role in the inflammatory process during the initiation phase and in the reconstruction and fibrosis process during the later phase. Recently, it has been proven that alveolar macrophages are constituted by morphologically, biochemically and immunologically heterogenous cell subpopulations. The possibility of alterations to these characteristics of the alveolar macrophage population during lung disease has been raised. To investigate such a possibility a hyperoxic rat lung model was made to check the distributional and morphological changes of rat alveolar macrophage subpopulation in acute hyperoxic lung injury. Method : Alveolar macrophage were lavaged from normal and hyperoxic lung injury rats and separated by discontinuous gradients of percoll. After cell counts of each density fraction were accessed, the morphomeric analysis of alveolar macrophages was performed on cytocentrifuged preparations by transmission electron micrograph. Result : 1. The total alveolar macrophage cell count significantly increased up to 24 hours after hyperoxic challenge (normal control group $171.6{\pm}24.1{\times}10^5$, 12 hour group $194.8{\pm}17.9{\times}10^5$, 24 hour group $207.6{\pm}27.1{\times}10^5$, p<0.05). oHoHH However the 48 hour group ($200.0{\pm}77.8{\times}10^5$) did not show a significant difference. 2. Alveolar septal thickness significantly increased up to 24 hours after hyperoxic challenge(normal control group $0.7{\pm}0.2{\mu}m$, 12 hour group $1.5{\pm}0.4{\mu}m$, 24 hour group $2.3{\pm}0.4{\mu}m$, p<0.05). However the 48 hour group did not show further change ($2.5{\pm}0.4{\mu}m$). Number of interstitial macrophage markedly increased at 24 hour group. 3. Hypodense fraction(fraction 1 and fraction 2) of alveolar macrophage showed a significant increase following hyperoxic challenge ($\beta=0.379$.$\beta=0.694$. p<0.05) ; however, fraction 3 was rather decreased following the hyperoxic challenge($\beta=0.815$. p<0.05), and fraction 4 showed an irregular pattern. 4. Electron microscopic observation of alveolar macrophage from each fraction revealed considerable morphologic heterogeneity. Cells of the most dense subfraction(fraction 4) were small, round, and typically highly ruffled with small membrane pseudopods. Cells of the least dense fraction (fraction 1) were large and showed irregular eccentric nucleus and high number of heterogenous inclusions. Conclusion : In conclusion, these results suggest that specific hypodense alveolar macrophage subpopulation may play a an important role in an acute hyperoxic lung injury model But further study, including biochemical and immunological function of these subpopulations, is needed.

• Tuberculosis and Respiratory Diseases
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• v.56 no.2
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• pp.203-209
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• 2004

Background : Methotrexate (MTX) has been used to treat a wide range of malignant and benign diseases including osteosarcoma, advanced stage non-Hodgkin's lymphoma, psoriasis, severe rheumatoid arthritis, sarcoidosis, and Wegener's granulomatosis. MTX-induced lung injury occurs in up to 10% of treated patients. Although both acute and chronic presentations have been described, typical manifestation of MTX-induced lung injury is subacute with symptoms usually developing within several months after starting therapy. Nonspecific interstitial pneumonia (NSIP) is the most common histopathologic manifestation of MTX-induced lung disease, while bronchiolitis obliterans organizing pneumonia (BOOP) and diffuse alveolar damage (DAD) are less common. Granuloma formation is reported in 34.7%. In Korea, Two reports of MTX pneumonitis have been published. The one presented with NSIP and the other with DAD. We recently experienced a case of MTX pneumonitis with presentation of hypersensitivity pneumonitis.

• Journal of Chest Surgery
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• v.32 no.5
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• pp.413-421
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• 1999

Background: Ischemia reperfusion injury is known to contribute to the major causes of the early graft failure in lung transplantation. Triiodothyronine (T3) has been suggested to ameliorate ischemia reperfusion injury from both in vivo and in vitro experiments of various organs. Prospecting its beneficial effect for pulmonary allograft preservation, we made a new solution by adding T3 into the extracellular type dextran solution. Material and Method: Twelve adult mongrel dogs underwent left lung allotransplantation. Six donor dogs were flushed with the new solution(Group 1, n=6), and the remaining six were flushed with Euro-Collins solution to serve as controls(Group 2, n=6). Allografts were stored in each preservation solution for 20 hours at 4$^{\circ}C$. Left single lung transplantations were performed. The right pulmonary artery and the right main bronchus were clamped at 15 minutes after the reperfusion and maintained throughout the experiment to evaluate the transplanted left lung function. Result: Arterial carbon dioxide tension was better in group 1 than in group 2 throughout the experiment period and the difference was statistically significant at 2 hours after reperfusion(28.0${\pm}$3.0 mmHg and 53.1${\pm}$17.4 mmHg, p<0.05). The differences of arterial oxygen partial pressure, peak airway pressure and pulmonary vascular resistance showed no statistical significance. The malondialdehyde(MDA) level, measured from tissue obtained at 120 minutes after reperfusion showed no statistically significant difference. The tissue wet/dry ratio of group 1(649${\pm}$27 %) was significantly lower than that of group 2(686${\pm}$71 %, p<0.05). The microscopic examination revealed varying degrees of injury represented mainly by findings such as perivascular neutrophil infiltration, capillary hemorrhage and interstitial congestion. These findings were less severe in group 1 than those in group 2. Conclusion: The new solution demonstrated superior allograft preservation after 20 hour ischemia compared to Euro-Collins solution in canine single left lung transplantation model, these results suggest that T3 might be a promising agent for pulmonary allograft preservation.