• Tuberculosis and Respiratory Diseases
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• v.60 no.4
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• pp.451-463
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• 2006

Background : Reactive oxygen species (ROS) take center stage as executers in ventilator-induced lung injury (VILI). The protein with DNA-damage scanning activity, poly (ADP-ribose) polymerase-1 (PARP1), signals DNA rupture and participates in base-excision repair. Paradoxically,overactivation of PARP1 in response to massive genotoxic injury such as ROS can induce cell death through ${\beta}$ -nicotinamide adenine dinucleotide ($NAD^+$) depletion, resulting in inflammation. The purpose of this study is to investigate the role of PARP1 and the effect of its inhibitor in VILI. Methods : Forty-eight male C57BL/6 mice were divided into sham, lung protective ventilation(LPV), VILI, and PARP1 inhibitor (PJ34)+VILI (PJ34+VILI) groups. Mechanical ventilator setting for the LPV group was $PIP\;15cmH_2O$ + $PEEP\;3cmH_2O$ + RR 90/min + 2 hours. The VILI and PJ34+VILI groups were ventilated on a setting of $PIP\;40cmH_2O$ + $PEEP\;0cmH_2O$ + RR 90/min + 2 hours. As a PARP1 inhibitor for the PJ34+VILI group, 20 mg/Kg of PJ34 was treated intraperitoneally 2 hours before mechanical ventilation. Wet-to-dry weight ratio and acute lung injury (ALI) score were measured to determine the degree of VILI. PARP1 activity was evaluated by using an immunohistochemical method utilizing biotinylated NAD. Myeloperoxidase (MPO) activity and the concentration of inflammatory cytokines such as tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$, and IL-6 were measured in bronchoalveolar lavage fluid (BALF). Results : In the PJ34+VILI group, PJ34 pretreatment significantly reduced the degree of lung injury, compared with the VILI group (p<0.05). The number of cells expressing PARP1 activity was significantly increased in the VILI group, but significantly decreased in the PJ34+VILI group (p=0.001). In BALF, MPO activity, $TNF-{\alpha}$, $IL-1{\beta}$, and IL-6 were also significantly lower in the PJ34+VILI group (all, p<0.05). Conclusion : PARP1 overactivation plays a major role in the mechanism of VILI. PARP1 inhibitor prevents VILI, and decreases MPO activity and inflammatory cytokines.

• Korean Journal of Poultry Science
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• v.38 no.1
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• pp.59-69
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• 2011

This study was conducted to investigate the effects of dietary supplementation of CS682, a fermentation product of Actinomycetae(Nocardia sp. CS682), and its commercial product DSC682$^{(R)}$ on the performance, blood parameters, intestinal microflora, and immune response in laying hens. Hy-Line Brown$^{(R)}$ laying hens were housed in two bird cages. Feeding trial lasted 5 wk under 16.5 h:7.5 h(L:D) lighting regimen. In Exp.1, a total of 480 birds of 86 wk old were assigned to four dietary treatments: Control, Antibiotics (6 ppm avilamycin), CS682-0.1 (CS682 0.1%) and CS682-1.0 (CS682 1.0% supplementation). Each treatment was replicated five times with 24 birds (or 12 cages) per replication. In Exp. 2, a total of 1,000 birds of 26 wk old were assigned to five dietary treatments: Control, Antibiotics (6 ppm avilamycin), DCS682-0.05 (DCS682 0.05%), DCS682-0.1 (DCS682 0.1%), DCS682-0.2 (DCS682 0.2% supplementation). Each treatment was replicated five times with 40 birds (or 20 cages) per replication. In Exp. 1, there were no significant differences among treatments in egg production, egg weight, broken & soft egg production, feed intake, and feed conversion ratio. Also, there were no significant differences among treatments in eggshell thickness, eggshell color and Haugh unit. However, eggshell strength was significantly (p<0.05) greater in CS682 and Antibiotics treatments than Control, and egg yolk color was significantly (p<0.05) higher in CS682-1.0 than Control. In Exp. 2, feed intake was significantly (p<0.05) lower in DSC682-0.05 than Control. Lightness(L) of Hunter Lab color of eggshell of DCS and Antibiotics treatments was significantly (p<0.05) lower than Control. Egg yolk color of DCS 0.1 and 0.2 treatments was significantly (p<0.05) higher than Control. Haugh unit increased significantly (p<0.05) in Antibiotics and DCS682-0.1 treatments. The immunoglobulin levels of plasma (IgG and IgA) and eggyolk (IgY) were not significantly affected by treatments. Antibiotics and CS682 or DCS682 treatments significantly (p<0.05 or 0.01) influenced some of the erythrocytes and leukocytes parameters in blood. In Exp.1, mean corpuscular volume (MCV) decreased by CS682 treatments and mean corpuscular hemoglobin (MCH) was highest in Antibiotics treatments. In Exp.2, the level of monocyte (MO) decreased in DCS682-0.10 and 0.20 treatments. The cfu of C. perfringens and S. typhimurium in small intestinal content were highest in Control and lowest in Antibiotics in both experiments. In Exp. 2, DSC682-0.05 and -0.1 treatments were highest and Antibiotic treatment was lowest in Lactobacilli spp. The results of the present layer experiments indicated that supplementation of 0.1~0.2% CS682 or DCS682 may increase eggshell strength, color of eggshell and eggyolk, Haugh unit, and control harmful intestinal microbes.

• Radiation Oncology Journal
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• v.19 no.1
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• pp.66-73
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• 2001

Purpose : For the research of Boron Neutron Capture Therapy (BNCT), fast neutrons generated from the MC-50 cyclotron with maximum energy of 34.4 MeV in Korea Cancer Center Hospital were moderated by 70 cm paraffin and then the dose characteristics were investigated. Using these results, we hope to establish the protocol about dose measurement of epi-thermal neutron, to make a basis of dose characteristic of epi-thermal neutron emitted from nuclear reactor, and to find feasibility about accelerator-based BNCT. Method and Materials : For measuring the absorbed dose and dose distribution of fast neutron beams, we used Unidos 10005 (PTW, Germany) electrometer and IC-17 (Far West, USA), IC-18, ElC-1 ion chambers manufactured by A-150 plastic and used IC-l7M ion chamber manufactured by magnesium for gamma dose. There chambers were flushed with tissue equivalent gas and argon gas and then the flow rate was S co per minute. Using Monte Carlo N-Particle (MCNP) code, transport program in mixed field with neutron, photon, electron, two dimensional dose and energy fluence distribution was calculated and there results were compared with measured results. Results : The absorbed dose of fast neutron beams was $6.47\times10^{-3}$ cGy per 1 MU at the 4 cm depth of the water phantom, which is assumed to be effective depth for BNCT. The magnitude of gamma contamination intermingled with fast neutron beams was $65.2{\pm}0.9\%$ at the same depth. In the dose distribution according to the depth of water, the neutron dose decreased linearly and the gamma dose decreased exponentially as the depth was deepened. The factor expressed energy level, $D_{20}/D_{10}$, of the total dose was 0.718. Conclusion : Through the direct measurement using the two ion chambers, which is made different wall materials, and computer calculation of isodose distribution using MCNP simulation method, we have found the dose characteristics of low fluence fast neutron beams. If the power supply and the target material, which generate high voltage and current, will be developed and gamma contamination was reduced by lead or bismuth, we think, it may be possible to accelerator-based BNCT.

• The Korean Journal of Nuclear Medicine
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• v.38 no.1
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• pp.85-98
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• 2004

Purpose: Cellular uptake of $^{99}mTc$-sestamibi (MIBI) and $^{99}mTc$-tetrofosmin (TF) is low in cancer cells expressing multidrug resistance(MDR) by p-glycoprotein(Pgp) or multidrug related protein(MRP). Verapamil is known to increase cellular uptake of MIBI in MDR cancer cells, but is recently reported to have different effects on tracer uptake in certain cancer cells. This study was prepared to evaluate effects of verapamil on cellular uptake of MIBI and TF in several cancer cells. Materials and Methods: Celluar uptakes of Tc-99m MIBI and TF were measured in erythroleukermia K562 cell, breast cancer MCF7 cell, and human ovarian cancer SK-OV-3 cells, and data were compared with those of doxorubicin-resistant K562(Ad) cells. RT-PCR and Western blot analysis were used for the detection of mdr1 mRNA and Pgp expression, and to observe changes in isotypes of PKC enzyme. Effects of verapamil on MIBI and TF uptake were evaluated at different concentrations upto $200{\mu}M\;at\;1{\times}10^6\;cells/ml\;at\;37^{\circ}C$. Radioactivity in supernatant and pellet was measured with gamma counter to calculate cellular uptake ratio. Toxicity of verapamil was measured with MTT assay. Results: Cellular uptakes of MIBI and TF were increased by time in four cancer cells studied. Co-incubation with verapamil resulted in an increase in uptake of MIBI and TF in K562(Adr) cell at a concentration of $100{\mu}M$ and the maximal increase at $50{\mu}M$ was 10-times to baseline. In contrast, uptakes of MIBI and TF in K562, MCF7, SK-OV3 cells were decreased with verapamil treatment at a concentration over $1{\mu}M$. With a concentration of $200{\mu}M$ verapamil, MIBI and TF uptakes un K562 cells were decreased to 1.5 % and 2.7% of those without verapamil, respectively. Cellular uptakes of MIBI and TF in MCF7 and SK-OV-3 cells were not changed with $10{\mu}M$, but were also decreased with verapamil higher than $10{\mu}M$, resulting 40% and 5% of baseline at $50{\mu}M$. MTT assay of four cells revealed that K562, MCF7, SK-OV3 were not damaged with verapamil at $200{\mu}M$. Conclusion: Although verapamil increases uptake of MIBI and TF in MDR cancer cells, cellular uptakes were further decreased with verapamil in certain cancer cells, which is not related to cytotoxicity of drug. These results suggest that cellular uptakes of both tracers might differ among different cells, and interpretation of changes in tracer uptake with verapamil in vitro should be different when different cell lines are used.

• Journal of Preventive Medicine and Public Health
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• v.4 no.1
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• pp.41-64
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• 1971

During the period from July 1st to the end of November 1970, a survey on air pollution and noise level was made in Seoul, Pusan and Taegu, the three largest cities in Korea. Each city was divided into 4-6 areas; the industrial area, the semi-industrial area, the commercial area, the residential area, the park area and the downtown area. Thirty eight sites were selected from each area. A. Method of Measurement : Dustfall was measured by the Deposit Gauge Method, sulfur oxides by $PbO_2$ cylinder method, suspended particles by the Digital Dust Indicator, Sulfur dioxide ($SO_2$) and Carbon Monoxide (CO) by the MSA & Kitakawa Detector and the noise levels by Rion Sound Survey meter. B. Results: 1. The mean value of dustfall in 3 cities was $30.42ton/km^2/month$, ranging from 8.69 to 95.44. 2. The mean values of dustfall by city were $33.17ton/km^2/month$ in Seoul, 32.11 in Pusan and 25.97 in Taegu. 3. The mean values of dustfall showed a trend of decreasing order of semi-industrial area, downtown area, industrial area, commercial area, residential area, and park area. 4. The mean value of dustfall in Seoul by area were $52.32ton/km^2/month$ in downtown, 50.54 in semi-industrial area, 40.37 in industrial area, 24,19 in commercial area, 16.25 in park area and 15.39 in residential area in order of concentration. 5. The mean values of dustfall in Pusan by area were $48.27ton/km^2/month$ in semi-industrial area, 36.68 in industrial area 25.31 in commercial area, and 18.19 in residential area. 6. The mean values of dustfall in Taegu by area were $36.46ton/km^2/month$ in downtown area, 33.52 in industrial area, 20.37 in commercial area and 13.55 in residential area. 7. The mean values of sulfur oxides in 3 cities were $1.52mg\;SO_3/day/100cm^2\;PbO_2$, ranging from 0.32 to 4.72. 8. The mean values of sulfur oxides by city were $1.89mg\;SO_3/day/100cm^2\;PbO_2$ in Pusan, 1.64 in Seoul and 1.21 in Taegu. 9. The mean values of sulfur oxides by area in 3 cities were $2.16mg\;SO_3/day/100cm^2\;PbO_2$ in industrial area, 1.69 in semi-industrial area, 1.50 in commercial area, 1.48 in downtown area, 1.32 in residential area and 0.94 in the park area, respectively. 10. The monthly mean values of sulfur oxides contents showed a steady increase from July reaching a peak in November. 11. The mean values of suspended particles was $2.89mg/m^3$, ranging from 1.15 to 5.27. 12. The mean values of suspended particles by city were $3.14mg/m^3$ in Seoul, 2.79 in Taegu and 2.25 in Pusan. 13. The mean values of noise level in 3 cities was 71.3 phon, ranging from 49 to 99 phon. 14. The mean values of noise level by city were 73 phon in Seoul, 72 in Pusan, and 69 in Taegu in that order. 15. The mean values of noise level by area in 3 cities showed a decrease in the order of the downtown area, commercial area, industrial area and semi-industrial area, park area and residential area. 16. The comparison of the noise levels by area in 3 cities indicated that the highest level was detected in the downtown area in Seoul and Taegu and in the industrial area in Pusan. 17. The daily average concentration of sulfur dioxides ($SO_2$) in 3 cities was 0.081 ppm, ranging from 0.004 to 0.196. 18. The daily average concentrations of sulfur dioxides by city were 0.092 ppm in Seoul, 0.089 in Pusan and 0.062 in Taegu in that order. 19. The weekly average concentration of carbon monoxides(CO) was 27.59 ppm. 20. The daily average concentrations of carbon monoxides by city were 33.37 ppm. in Seoul, 25.76 in Pusan and 23.65 in Taegu in that order. 21. The concentration of $SO_2$ and CO reaches a peak from 6 p. m. to 8 p. m. 22. About 3 times probably the daily average concentration of CO could be detected in the downtown area probably due to heavy traffic emission in comparison with that in the industial area. 23. As for daily variation of the concentration of $SO_2$ and CO it was found that the concentration maintains relatively higher value during weekdays in the industrial area and on the first part of the week in the downtown area.

• Journal of Preventive Medicine and Public Health
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• v.4 no.1
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• pp.65-76
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• 1971

In view of ever rising water pollution problems of river in the vicinity of large urban communities, the author has made an investigation on the pollution of water sampled from Han River (Seoul area) and Nakdong River (Daegu city area) during the period from July to December, 1970. The water samples were taken twice a month during the study period of 6 months from 7 points (locations) along the main stream of Han River at Seoul city and 5 points of Nakdong River at Daegu city. The samples ware measured and analyzed in accordance with the recognized methods in the 'Standard Methods for Examination of Water and waste' by American Public Health Association. The obtained results are as follows : I. Han River. 1. Average turbidity was 5.1 units ranging from 1 to 10 units and the turbidity of down stream was higher than that of the upper stream. 2. pH value showed slight alkalinity (mean;7.2) except Yunchang-Dong (6.9). 3. The mean value of Dissolved Oxygen contents (D.O) was 7.2 ppm. (range of 3.4-10.5ppm.). D.O. of the upper stream (8.2 ppm. at Walker Hill boating place, 8.0 ppm. at the Gwangzang Bridge and Ddookdo) was higher than that of he downstream (5.6ppm. at Yumchang-Dong, 6.4 ppm. at the 2nd Han River Bridge), and D.O. in the winter season was higher than that in the summer season, respectively. 4 The mean value of the Biochemical Oxygen Demand (B.O.D.) was 28.3 ppm. (range of 6.2-64.8 ppm.). The mean value of B.O.D. was 48.7 ppm. at Yumchang-Dong, 42.3 ppm. at the 2nd Han River Bridge, 34.0 ppm. at the 1st nan River Bridge, 28.5 ppm. at the 3rd Han River Bridge, 19.2 ppm. at Dookdo, 13.2 ppm. at the Gwangzang Bridge, and 10.2 ppm. at the Walker Hill boating place in order of value. B.O.D. in July and August (35.6 and 34.5 ppm.) were the highest and that in November and December (18.6 and 21.2 ppm.) were the lowest. 5. Suspended Solids (SS) were from 15.0 to 667.0 ppm. with the mean of 222.1 ppm. 'Suspended Solids' of the water samples at Yumchang-Dong and the 2nd Han River Bridge were found to be 378.1 ppm. and 283.9 ppm. respectively which were higher than at the Gwangzang Bridge (134.1 ppm.) and at Walker Hill boating place (79.3ppm.). 6. Coliform colonies counting of the water samples ranged from $0-2,500{\times}10/100ml$. with the mean value of $205.6{\times}10/100ml$. The most contaminated water sample by coliform were from the point of the 2nd Han River Bridge with $640.8{\times}10/100ml$ while the lowest ones were from Walker Hill boating place with $17.2{\times}10/100ml$. There was also a seasonal variation in coliform contamination that is the higher in summer and the lower in winter. II. Nakdong River 1. The mean value of turbidity was 2.3 units with range of 0 to 9.0 units. The highest point was at Geumho River (7.2 units). and the lowest point was at Gangzung and Moonsan (0.45 and 0.41 units). 2. The mean value of pH was 7.5 (range of 7.1-8.5) and highest point was Geumho River with 8.5. 3. The mean value of D.O. was 8.1 ppm. (range of 3.4-11.2 ppm.). D.O. of the upper stream showed higher value than that of the down stream, and the winter season than the summer season. 4. B.O.D. ranged from 2.6 to 57.0 ppm. (mean; 20.4ppm.). The water sample at Geumho River showed the highest value (41.5 ppm.) while at Moonsan and Gangzung showed the lowest (4.6 and 4.7 ppm.). 5. The mean value of suspended solids was 48.7 ppm. (range of 4.0-182.0 ppm.). The highest month was July (63.7ppm.) and August (62.1 ppm.) and the lowest month was October (37.0 ppm.) and December (24.4 ppm.). 6. The mean value of the coliform colonies was $22.7{\times}10/100ml$. (range of $0-243{\times}10/100ml$.). The highest number of the colonies was found in the sample water at the Whawon recreation area ($50.5{\times}10/100ml$.) followed by the Geumho River ($33.9{\times}10/100ml$.), the Goryung Bridge ($28.3{\times}10/100ml$.), Gangzung($0.7{\times}10/100ml$), and Moonsan ($0.6{\times}10/100ml$.).

• Tuberculosis and Respiratory Diseases
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• v.50 no.2
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• pp.182-195
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• 2001

Background : Idiopathic pulmonary fibrosis(IPF) is a devastating illness for which there is little effective treatment. The key cytokines currently implicated in the fibrotic process are the transforming growth factor-${\beta}_1$(TGF-${\beta}_1$), tumor necrosis factor-$\alpha$(TNF-$\alpha$), endothelin-1(ET-1) and interferon-$\gamma$(IFN-$\gamma$). The rat model for paraquat-induced pulmonary fibrosis was chosen to investigate the role of ET-1 in this disease. Both ET-1 and TGF-${\beta}_1$ expression in lung lesions were examined using immunohistochemical staining. After $Bosentan^{(R)}$ administration, an orally active ET-$l_A$ and ET-$1_B$ receptor antagonist, the degree of pulmonary fibrosis and ET-1 and TGF-${\beta}_1$ expression were analyzed. Method : Sprague-Dawley rats were divided into three groups, the control group, the fibrosis group, and the fibrosis-$Bosentan^{(R)}$-treated group. The animals were sacrificed periodically at 1, 3, 5, 7, 10, 14 days after administering saline or paraquat. The effects between groups were compared with the results of light microscopy and immunohistochemical staining for ET-1 and TGF-${\beta}_1$. The degree of fibrosis was evaluated by H&E and Masson's trichrome staining, which were graded by a computerized image analyzer. The degree of immunohistochemical staining was categorized by a semi-quantitative analysis method. Results : The lung collagen content had increased in the paraquat instillated animals by day 3, and continued to increase up to day 14. A daily treatment by gavage with $Bosentan^{(R)}$ (100mg/kg) did not prevent the increase in collagen deposition on the lung that was induced by paraquat instillation. There were increased immunohistochemical stains of ET-1 on the exudate, macrophages, vascular endothelial cells and pneumocytes in the paraquat instillated group. Furthermore, TGF-${\beta}_1$ expression was higher on the exudate, macrophages, some inflammatory cells, pneumocytes( type I, and II), vascular endothelium and the respiratory epithelial cells around the fibrotic area. After Bosentan treatment, there were no definite changes in ET-1 and TGF-${\beta}_1$ expression. Conclusion : Fibrosis of the Paraquat instillated group was more advanced when compared with the control group. In addition, there was increased ET-1 and TGF-${\beta}_1$ expression around the fibrotic area. ET-1 is associated with lung fibrosis but there was little effect of the ET-1 receptor blocker($Bosentan^{(R)}$) on antifibrosis.Background : Idiopathic pulmonary fibrosis(IPF) is a devastating illness for which there is little effective treatment. The key cytokines currently implicated in the fibrotic process are the transforming growth factor-${\beta}_1$(TGF-${\beta}_1$), tumor necrosis factor-$\alpha$(TNF-$\alpha$), endothelin-1(ET-1) and interferon-$\gamma$(IFN-$\gamma$). The rat model for paraquat-induced pulmonary fibrosis was chosen to investigate the role of ET-1 in this disease. Both ET-1 and TGF-${\beta}_1$ expression in lung lesions were examined using immunohistochemical staining. After $Bosentan^{(R)}$ administration, an orally active ET-$1_A$ and ET-$1_B$ receptor antagonist, the degree of pulmonary fibrosis and ET-1 and TGF-${\beta}_1$ expression were analyzed. Method : Sprague-Dawley rats were divided into three groups, the control group, the fibrosis group, and the fibrosis-$Bosentan^{(R)}$-treated group. The animals were sacrificed periodically at 1, 3, 5, 7, 10, 14 days after administering saline or paraquat. The effects between groups were compared with the results of light microscopy and immunohistochemical staining for ET-1 and TGF-${\beta}_1$. The degree of fibrosis was evaluated by H&E and Masson's trichrome staining, which were graded by a computerized image analyzer. The degree of immunohistochemical staining was categorized by a semi-quantitative analysis method. Results : The lung collagen content had increased in the paraquat instillated animals by day 3, and continued to increase up to day 14. A daily treatment by gavage with $Bosentan^{(R)}$ (100mg/kg) did not prevent the increase in collagen deposition on the lung that was induced by paraquat instillation. There were increased immunohistochemical stains of ET-1 on the exudate, macrophages, vascular endothelial cells and pneumocytes in the paraquat instillated group. Furthermore, TGF-${\beta}_1$ expression was higher on the exudate, macrophages, some inflammatory cells, pneumocytes( type I, and II), vascular endothelium and the respiratory epithelial cells around the fibrotic area. After Bosentan treatment, there were no definite changes in ET-1 and TGF-${\beta}_1$ expression. Conclusion : Fibrosis of the Paraquat instillated group was more advanced when compared with the control group. In addition, there was increased ET-1 and TGF-${\beta}_1$ expression around the fibrotic area. ET-1 is associated with lung fibrosis but there was little effect of the ET-1 receptor blocker($Bosentan^{(R)}$) on antifibrosis.