• Toxicological Research
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• v.26 no.2
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• pp.137-147
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• 2010

Pulmonary fibrosis is a common consequence of many lung diseases and a leading cause of morbidity and mortality. The molecular mechanisms underlying the development of pulmonary fibrosis remain poorly understood. One model used successfully to study pulmonary fibrosis over the past few decades is the bleomycin-induced pulmonary fibrosis model. We aimed to identify the genes associated with fibrogenesis using an Affymetrix GeneChip system in a bleomycin-induced rat model for pulmonary fibrosis. To confirm fibrosis development, several analyses were performed, including cellular evaluations using bronchoalveolar lavage fluid, measurement of lactate dehydrogenase activity, and histopathological examinations. Common aspects of pulmonary fibrosis such as prolonged inflammation, immune cell infiltration, emergence of fibroblasts, and deposition of extracellular matrix and connective tissue elements were observed. Global gene expression analysis revealed significantly altered expression of genes ($\geq$ 1.5-fold, p < 0.05.) in a time-dependent manner during the development of pulmonary fibrosis. Our results are consistent with previous results of well-documented gene expression. Interestingly, the expression of triggering receptor expressed on myeloid cells 2 (Trem2), secreted phosphoprotein 1 (Spp1), and several proteases such as Tpsab1, Mcpt1, and Cma1 was considerably induced in the lung after bleomycin treatment, despite little evidence that they are involved in pulmonary fibrogenesis. These data will aid in our understanding of fibrogenic mechanisms and contribute to the identification of candidate biomarkers of fibrotic disease development.

• Laboraroty Animal Research
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• v.33 no.2
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• pp.76-83
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• 2017

Chronic obstructive pulmonary diseases (COPD) is an important disease featured as intense inflammation, protease imbalance, and air flow limitation and mainly induced by cigarette smoke (CS). In present study, we explored the effects of $Pycnogenol^{(R)}$ (PYC, pine bark extract) on pulmonary fibrosis caused by CS+lipopolysaccharide (LPS) exposure. Mice were treated with LPS intranasally on day 12 and 26, followed by CS exposure for 1 h/day (8 cigarettes per day) for 4 weeks. One hour before CS exposure, 10 and 20 mg/kg of PYC were administered by oral gavage for 4 weeks. PYC effectively reduced the number of inflammatory cells and proinflammatory mediators caused by CS+LPS exposure in bronchoalveolar lavage fluid. PYC inhibited the collagen deposition on lung tissue caused by CS+LPS exposure, as evidenced by Masson's trichrome stain. Furthermore, transforming growth $factor-{\beta}1$ ($TGF-{\beta}1$) expression and Smad family member 2/3 (Smad 2/3) phosphorylation were effectively suppressed by PYC treatment. PYC markedly reduced the collagen deposition caused by CS+LPS exposure, which was closely involved in $TGF-{\beta}1$/Smad 2/3 signaling, which is associated with pulmonary fibrotic change. These findings suggest that treatment with PYC could be a therapeutic strategy for controlling COPD progression.

• Journal of Preventive Medicine and Public Health
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• v.37 no.4
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• pp.329-336
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• 2004

Objectives : Iron (Fe) is an essential element in biological processes; however excessive Fe is harmful to human health. Some air pollutants contain a high level of Fe, and the human lung could therefore be over-exposed to Fe through inhaled air pollutants. This study was performed to investigate the role of metal transporters (divalent metal transporter 1, DMT1, and metal transporter protein 1, MTP1) in the lung under the environments of Fe deficiency in the body and Fe over-exposure in the lung. Methods : Rats were fed Fe deficient (FeD, 2-6 mg Fe/kg) or Fe supplemented (FeS, 120 mg Fe/kg) diet for 4 weeks, followed by a single intratracheal instillation of ferrous sulfate at low (10 mg/kg) or high (20 mg/kg) dose. Fe concentration was analyzed in the serum, lung and liver, and histopathological findings were observed in the lung at 24 hours after Fe administration. The level of DMT1 and MTP1 expression in the lung was analyzed by RT-PCR. Also, the effect of Fe deficiency in the body was evaluated on the level of Fe concentration and metal transporters compared to FeS-diet fed rats at the end of 4-week FeD or FeS diet. Results : The 4-week FeD diet in rats induced an Fe deficiency anemia with decreased serum total Fe, increased unsaturated Fe binding capacity and hypochromic microcytic red blood cells. The concentration of Fe in the lung and liver was lower in the FeD-diet fed rats than in the FeS-diet fed rats. The level of metal transporters mRNA expression was higher in the FeD-diet fed rats than in the FeS-diet. The concentration of Fe in the lung was increased in a dose-dependent pattern after intratracheal instillation of Fe into the rats, while the level of Fe in the serum and liver was not increased in the low-dose Fe administered rats. Therefore, DMT1 and MTP1 mRNA was highly expressed in both FeD-diet and FeS-diet fed rats, after intratracheal instillation of Fe. Conclusions : DMT1 and MTP1 mRNA were more highly expressed in FeD-diet fed rats than in FeS-diet fed rats. The over-exposure of Fe intratracheally induced high expression of metal transporters and increased Fe deposition in the lung in both FeD-diet and FeS-diet fed rats, but did not increase the Fe level of the serum and liver in low-dose Fe administered rats. These results suggest that the role of metal transporters in the lung might be different in a part from the duodenum under the environment of over-exposure to Fe.

• Journal of Chest Surgery
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• v.40 no.7 s.276
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• pp.467-472
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• 2007

Background: Lung transplantation is the definitive therapy for end stage lung disorders. The success of allogenic lung transplantation has led to an increasing shortage of donor lungs from humans, including cadavers, and attention has now turned to transplantation of lungs from other species. However, there are many biological hurdles when using organs from other species because of hyperacute rejection after discordant xenotransplantation. Material and Method: Pigs (n=6, weighing $20{\sim}30kg$ each) for the donors and mongrel dogs (n=6, weighing $20{\sim}28kg$ each) for the recipients were used in this experiment. The left kidney of a pig was perfused to a mongrel dog for 30 minutes through the femoral artery and vein of the dog, and the right kidney was perfused for 30 minutes sequentially. Then, both lungs of the pig were perfused to the dog through the pulmonary artery and left atrium with using the same time intervals. The levels of IgM and IgG were measured from the blood and specimens of the kidney and lung. Result: The average levels of serum IgM gradually decreased after the perfusion, but the average levels of serum IgG did not charge from before to after perfusion. The immunohistochemical findings revealed decreased deposition of IgG and IgM after the perfusion. Conclusion: We conclude that the levels of the serum natural antibodies would be decreased with pre-transplantation xenograft perfusion in the recipient and the occurrence rate of hyperacute rejection after transplantation would be decreased.

• Korean Journal of Veterinary Research
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• v.12 no.1
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• pp.121-126
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• 1972

The pneumonic lungs of 51 pigs, from which the presence of pasteurella organisms was confirmed by bipolar staining, were examined pathologically. The numbers of pigs in each age group were 22 (43.1%) in 3-4 month group, 20 (39.2%) in 1-2 month group, 7 (13.7%) in 5-6 month group, and 2 (4.0%) in group of more than one year. The lungs of 16 pigs which were regarded as pasteurella pneumonia without any other manifestations were studied pathogically. Grossly, the affected lungs showed pulmonary edema, lobular consolidation and interlobular edema. Pigs over 3 months of age frequently showed chronic condition in which the entire lobe was involved as confluent pneumonia. In such pneumonic lungs, infarction and focal necrosis of the lung parenchyma and deposition of fibrinous exudate on the pleura were encountered. Histologically, the alveolar spaces were filled with fibrinous and leukocytic exudates. The interlobular septae showed marked edema and fibrinous exudate. The process of organization was frequently observed in chronic cases.

• Korean Journal of Veterinary Research
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• v.5 no.1
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• pp.21-25
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• 1965

Throughout the studies the followings were obtained and summarized here. 1. Thickenings of plerua were due to the organized fibrin deposition on the pleural surface. 2. Thickenings of plerura were accompanied with increaseness of fibrous connective tissues in the interlobular and alveolar septa. 3. Eosinophilic inclusions seemed to LCL bodies were observed in the cytoplasms of epithelial cells of bronchi, bronchial glands and in the cytoplasms of mononuclear cells. 4. Histo-pathologically, there were some evidences influenced by viruses and the organisms of Psittacosis-Lymphogranuloma Venereum Group.

• Clinical and Experimental Pediatrics
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• v.48 no.10
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• pp.1038-1049
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• 2005

Asthma is characterized by a chronic inflammatory disorder of the airways that leads to tissue injury and subsequent structural changes collectively called airway remodelling. Characteristic changes of airway remodelling in asthma include goblet cell hyperplasia, deposition of collagens in the basement membrane, increased number and size of microvessels, hypertrophy and hyperplasia of airway smooth muscle, and hypertrophy of submucosal glands. Apart from inflammatory cells, such as eosinophils, activated T cells, mast cells and macrophages, structural tissue cells such as epithelial cells, fibroblasts and smooth muscle cells can also play an important effector role through the release of a variety of mediators, cytokines, chemokines, and growth factors. Through a variety of inflammatory mediators, epithelial and mesenchymal cells cause persistence of the inflammatory infiltrate and induce airway structural remodelling. The end result of chronic airway inflammation and remodelling is an increased thickness of the airway wall, leading to a increased the bronchial hyperresponsiveness and fixed declined lung function.

• Korean Journal of Veterinary Research
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• v.7 no.2
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• pp.25-30
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• 1967

Pathological studies, on the lung of 27 cases of bovine parasitic bronchitis which were secured from abattoirs in Korea, were performed and discussed. The chief pathological findings were as follows. Grossly, the lungs were shown various degree of lobular consolidation, collapse and alveolar emphysema around the bronchi in which nematodes of Dictyocaulus viviparus were present. Emphysema and edema were observed in the interlobular septa. The lesions were encountered mostly in the caudal and ventral borders of the diaphragmatic lobes. In all the cased of parasitic bronchitis in which thickening of the visceral pleura and fibrinous deposition on the pleural surfaces were not seemed to be entirely due to the lungworm infection. Microscopically, bronchopneumonia, peribronchial and peribronchiolar lymphoid hyperplasia, lympho-reticular broncho-occlusive legion, and bleakthrough lesion were examined in the affected lungs.

• The Korean Journal of Nuclear Medicine
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• v.24 no.2
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• pp.237-243
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• 1990

Pulmonary embolism demands rapid and accurate diagnosis. And ventilation imaging has greatly improved the diagnostic accuracy of pulmonary embolism in addition to perfusion imaging. Agents currently used include xenon-133, krypton-81m and technetium-99m radioaerosols. However radioactive gases are compromised by availability and cost for krypton-81m, radiation dose, gamma energy and non?physiologic behaviour for xenon-133. Radioaerosols of technetium-99m componds are rapidly cleared from the lung after inhalation, and their relative low effeciency (specific radioactivity) and wide distribution of particle sizes make them also suboptimum. A new ventilation agent, Technegas is a suspension of structured graphite ellipsoids with diameter below 20nm, labelled with $^{99m}Tc$ in a carrier gas of Argon. This report describes the authors' clinical experience with Technegas. This is the first reported clinical study of this agent in Korea. A comparison of Technegas and $^{99m}Tc-DTPA$ aerosol was performed in 12 patients with various pulmonary diseases such as COPD, pulmonary tuberculosis and pleural effusion. All patients were studied with $^{99m}Tc-DTPA$ aerosol inhalation and Technegas ventilation. In both studies image quality was assessed (1) semiquantitatively by scoring bronchial and gastric activity, (2) subjectively by direct visual comparison of peripheral lung images and (3) quantitatively by computing the peripheral penetration index(PI) for each lungs. The bronchial activites were seen in 7 out of 12 cases with $^{99m}Tc-DTPA$ aerosol and in 5/12 with Technegas. The gastric activities were seen in 5/12 and 1/12 cases respectively. The average values of PI were 61.26% with $^{99m}Tc-DTPA$ aerosol and 69.20% with Technegas (p>0.05). Using $^{99m}Tc-DTPA$ aerosol, COPD patients showed deposition in the central airways with poor visualization of the peripheral areas of the lungs. In Technegas studies these phenomena were less prominent, and the examination is well tolerated by pateients and requires only a minimum of patient cooperation. With superiority of easy availability and handling, better physical characteristics and favorable Image quality, Technegas is a Promising agent for lung ventilation scanning.

• Tuberculosis and Respiratory Diseases
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• v.40 no.4
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• pp.357-366
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• 1993

Background: Lung clearance of inhaled $^{99m}Tc$-DTPA reflects alveolar epithelial permeability and it had been reported as more sensitive than conventional pulmonary function tests in detecting lung epithelial damage. However, measuring lung clearance of inhaled $^{99m}Tc$-DTPA by gamma camera may not always reflect alveolar epithelial permeability exactly because it is influenced by mucociliary clearance depending on the site of particle deposition. Moreover, this method takes much time and patient's effort because he has to sit or lie still in front of the camera for a prolonged period. Most of the absorbed DTPA is excreted in urine within 24 hours and the amount of excreted DTPA in urine during the first few hours after inhalation is influenced by absorption rate which is correlated with the alveolar-epithelial permeability suggesting that the urinary excretion, especially in first few hours, may be an alternate index for lung clearance. The purpose of this study was to evaluate the usefulness of ratio of excreted $^{99m}Tc$-DTPA in 2 hour and 24 hour urine as an index of alveolar-epithelial damage. Methods: Pulmonary function tests including diffusing capacity and lung clearance of $^{99m}Tc$-DTPA measured by gama camera ($T_{1/2}$) and 2hr/24hr urine excretion ratio (Ratio) of inhaled $^{99m}Tc$-DTPA in 8 normal subjects and 14 patients with diffuse interstitial lung disease were compared. Results: 1) In the normal control, there was significant negative correlation between the $T_{1/2}$ and the Ratio (r=-0.77, p<0.05). In patients with diffuse interstitial lung disease, there also was significant negative correlation between $T_{1/2}$ and Ratio(r=-0.63, p<0.05). 2) In diffuse interstitial lung disease patients, the $T_{1/2}$ was $38.65{\pm}11.63$ min which was significantly lower than that of normal control, $55.53{\pm}11.15$ min and the Ratio was $52.15{\pm}10.07%$ also signifantly higher than that of the normal control, $40.43{\pm}5.53%$ (p<0.05). 3) There was no significant correlations between $T_{1/2}$ or Ratio and diffusing capactiy of lung in both patients and controls (p>0.05). Conclusion: These results suggests that 2hr/24hr urine excretion ratio of inhaled $^{99m}Tc$-DTPA is a useful simple bedside test in assessing alveolar epithelial permeability and that it may be used as an additive follow-up test in patients with diffuse interstitial lung disease complementing conventional pulmonary function tests.