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The Clinical Characteristics of Lung Cancer in Patients with Idiopathic Pulmonary Fibrosis (특발성 폐섬유화증에 동반된 폐암 환자의 임상적 특정)

  • Park, Joo-Hun;Lee, Jin-Seong;Song, Koun-Sik;Shim, Tae-Sun;Lim, Chae-Man;Koh, Youn-Suck;Lee, Sang-Do;Kim, Woo-Sung;Kim, Won-Dong;Kim, Dong-Soon
    • Tuberculosis and Respiratory Diseases
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    • v.46 no.5
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    • pp.674-684
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    • 1999
  • Background : It has been generally known that the incidence of lung cancer is higher in the patients with idopathic pumonary fibrosis (IPF) than those in general population. The reported incidence was variable from 4.8 to 43.2%. There were controversies on the most frequent cell type (squamous cell carcinoma vs. adenocarcinoma) and no study was done about the real concordance of cancer and the fibrotic lesion. And the pulmonary fibrosis may influence not only the development of cancer but also the treatment and prognosis of the cancer, but there was no report on that point. Method : Total 63 patients ($66.8{\pm}7.8$ year, M : F=61 : 2) were diagnosed as IPF combined with lung cancer (IFF-CA) at Asan Medical Center. A retrospective analysis was done about the risk factors of the lung cancer, pulmonary function test, the site of cancer(especially the relationship of the cancer with the fibrotic lesion), the histologic types, and the stage of cancer. The histologic types were compared with those of 2,660 patients with lung cancer who were diagnosed at the same institute for the same period. The effect of IPF on the treatment of the cancer was evaluated with the survival time after the detection of lung cancer. Results : The lung cancer was found in 63(22.9%) out of 281 patients with IPF. But in most of them(45 patients), lung cancer was detected at the same time with IPF and only in 18 patients, the cancer was diagnosed during the follow-up($25.2{\pm}17.7$ months) of IPF. So in our study, 6.7% of patients with IPF developed lung cancer during the course of the disease. The age ($66.8{\pm}7.84$ vs. $63.4{\pm}11.1$ years), percentage of smoker (88.9 vs. 67.2%), and the male gender (96.8 vs. 67.6%) were significantly higher in IPF-CA compared with lone IPF (p<0.05). The odds ratio of smoking was 4.7 compared with non smoking IPF controls. The lung cancer was located more frequently in the upper lobe and 55.5% was in the periphery of lung. The cancer was developed in the fibrotic lesion in 23 patients (35.9%), and in the majority of the patients, the cancer was separated from the fibrosis. The cell type of the lung cancer in IPF-CA was squamous cell carcinoma 34.9%, adenocarcinoma 30.2%, small cell carcinoma 19.0%, large cell undifferenciated carcinoma 6.3%, and others 9.5%. No significant difference in the distribution of histologic type of the lung cancer was found between IPF-CA and lone lung cancer. There was no significant difference in demographic features, cell types, location and the stage of the cancer between the group with concurrent IPF-CA and the group with cancer diagnosed during the follow up of IPF. There was a tendency (but statistically not significant : p=0.081) of higher incidence of adenocarcinoma among the cancers developed in the fibrotic area(43.5%) (F-CA) than in the cancers in non-fibrotic area (22.5%) (NF-CA). The prognosis of the patients with F-CA was poor (median survival : 4 months) compared with the patients with NF-CA (7 months, p=0.013), partly because the prevalence of severe IPF (the extent of fibrosis in HRCT 50%) was higher in F-CA group. Conclusion : These data suggest that the lung cancer in the patients with IPF has similar features to the ordinary lung cancer.

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Matrix Metalloproteinase in Idiopathic Pulmonary Fibrosis (특발성 폐섬유화증환자의 기관지폐포세척액 및 폐포대식세포 배양액의 Matrix metalloproteinase의 변화)

  • Park, Joo-Hun;Shim, Tae-Sun;Lim, Chae-Man;Koh, Youn-Suck;Lee, Sang-Do;Kim, Woo-Sung;Kim, Won-Dong;Kim, Dong-Soon
    • Tuberculosis and Respiratory Diseases
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    • v.51 no.4
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    • pp.303-314
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    • 2001
  • Background : Matrix metalioproteinase(MMP)-2 and MMP-9 have been known to play an important role in cell migration and the tissue remodeling process by type IV collagen lysis, a major component of the basement membrane. Intra-alveolar fibrosis, secondary to an injury to the basement membrane of the alveolar epithelial lining, is a major process in the pathogenesis of idiopathic pulmonary fibrosis(IPF). Therefore, MMP-2 and MMP-9 was hypothesized to play an important role in IPF pathogenesis. As a result, their level may reflect the activity or prognosis. Method : Forty one progressive IPF patients(age $59.82{\pm}1.73$ years, M:F=23:18), 16 patients with stable IPF for more than one year without therapy(age : $63.6{\pm}2.8$ years, M:F=13:3), and 7 normal controls were enrolled in this study. The MMP-2 and MMP-9 levels in the BAL fluid and alveolar macrophage conditioned media(AM-CM) were measured by zymography and the TIMP-1 level was measured by ELISA. Results : 1) The MMP-2 level in BALF was highest in the progressive IPF group ($1.36{\pm}0.28$) followed by the stable group ($0.46{\pm}0.13$) and the controls ($0.08{\pm}0.09$), which was statistically significant. The MMP-9 level of the IPF ($0.31{\pm}0.058$) and the stable group ($0.22{\pm}0.078$) were higher than that of the control group ($0.002{\pm}0.004$). In the AM-CM, only MMP-9 was detected, which was significantly higher in IPF group ($0.80{\pm}0.1O$) than in the control group($0.23{\pm}0.081$). The TIMP-1 level was also higher in both the IPF ($36.34{\pm}8.62\;{\mu}g/ml$) and stable group ($20.83{\pm}8.53\;{\mu}g/ml$) compared to the control group ($2.80{\pm}1.05\;{\mu}g/ml$) (p<0.05). 3) There was a correlation between the MMP-2 level in the BALF with the total cell number(r=0.298) and neutrophils(r=0.357) (p<0.05), and the MMP-9 level with the number of neutrophils (r=0.407) and lymphocytes (r=0.574)(p<0.05). The TIMP-1 level correlated with the total number of cell (r=0.338, p<0.05) and neutrophils(r=0.449, p=0.059). Conclusion : Both MMP and TIMP appear to play an important role in IPF pathogenesis, and their level may reflect the disease activity.

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A Randomized, Double-Blind Study to Assess the Efficacy and Safety of Oral LB20304 (Gemifloxacin) at Doses of 160mg or 320mg (Equivalent to 200mg or 400mg of the Mesylate Salt) Once Daily for 7 Days for the Treatment of Acute Exacerbations of Chronic Bronchitis (AECB) in Korean Adult Population (한국인에서 만성기관지염의 급성악화를 치료하기 위한 LB20304(Gemifloxacin) 160mg 또는 320mg 1일 1회 7일간 투여의 유효성과 안전성에 대한 연구)

  • Kim, Young Whan;Shim, Young-Soo;Kim, Won Dong;Shim, Tae Sun;Kang, Hong Mo;Choi, ByoungWhui;Kim, Jae-Yeol;Kwon, O Jung;Kim, Hojoong;Kim, Ju Ock;Jung, Ki-Suck;Hyeon, In Gyou;Mo, Eun Kyung;Lee, Seung-Joon;Nam, Gui Hyun;Lee, Kye Young;Park, Jae Seuk
    • Tuberculosis and Respiratory Diseases
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    • v.55 no.1
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    • pp.69-87
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    • 2003
  • Background : LB20304(gemifloxacin) is a new fluoroquinolone antibacterial agent with excellent activity against both Gram-negative and Gram-positive organisms. In vitro studies using clinical isolates have shown gemifloxacin to be highly active against penicillin-resistant strains of S. pneumoniae and in contrast to other reference quinolones, gemifloxacin retained good activity against clinical isolates of S. pneumoniae that were resistant to other members of the quinolone class. Therefore, gemifloxacin is thought to be effective in treating acute bacterial exacerbation of chronic bronchitis(AECB). The objective of this study was to evaluate the efficacy and safety of oral gemifloxacin at doses of 160mg or 320mg once daily for 7 days for the treatment of AECB in Korean adult population. Methods : This was a randomized, multicenter, double-blind, parallel group Phase II study to assess the clinical and antibacterial efficacy and safety of oral gemifloxacin for the treatment of AECB. Treatment Group A (67 patients) took oral gemifloxacin 160mg once daily for seven days and treatment Group B (70 patients) took oral gemifloxacin 320mg once daily for seven days. Results : The demographic profiles of the two treatment groups were similar. The clinical response at follow-up was 84.2% in the gemifloxacin 160-mg group, and 88.7% in the gemifloxacin-320 mg group, showing no statistically significant difference between two treatment groups(p=0.49). The clinical response at the end of therapy was 96.5% in the 160-mg group, and 96.4% in the 320-mg group. The bacteriological response at the end of therapy and follow-up were 81.8% and 78.9%, respectively, in the 160-mg group, and 86.4% and 84.2%, respectively, in the 320-mg group, showing no statistically significant difference between two treatment groups(p=0.68 and 0.68, respectively). S. pneumoniae(12 isolates) and H. influenzae(10 isolates) were the most prevalent pathogens. The MICs were lower for gemifloxacin than other quinolones against these key pathogens, and for S. pneumoniae, the MICs for gemifloxacin were considerably lower(${\leq}0.03$ ug/mL) than those for other quinolones, beta-lactams and macrolides. In the period on-therapy plus 30 days post-therapy, a total of 18 patients(26.9%) in the gemifloxacin 160mg group and 22 patients(31.4%) in the 320mg group reported at least one adverse event(AE). The most frequently reported AE was abdominal pain(3/67 patients, 4.5%) in the gemifloxacin 160mg group and increased level of hepatic enzyme(5/70 patients, 7.1%) in the 320mg group. The overall AE profiles for the two treatment groups were similar. Two out of 67 patients(3.0%) in the gemifloxacin 160mg group and 1/70 patients(1.4%) in the 320mg group reported at least one serious AE, however, none of which was considered by the investigator to be of suspected or probable relationship to study medication. Conclusion : The results of this study showed that gemifloxacin at doses of 160mg or 320mg once daily for 7 days in the treatment of acute exacerbations of chronic bronchitis(AECB) in adult Koreans was a very effective and safe treatment both clinically and bacteriologically.

A Comparison of Tiotropium 18㎍, Once Daily and Ipratropium 40㎍, 4 Times Daily in a Double-Blind, Double-Dummy, Efficacy and Safety Study in Adults with Chronic Obstructive Pulmonary Disease (만성폐쇄성폐질환 환자에서 Tiotropium 1일 1회, 1회 18㎍ 요법과 Ipratropium 1일 4회, 1회 40㎍ 요법의 치료효과 및 안전성 비교)

  • Kim, Seung Joon;Kim, Myung Sook;Lee, Sang Haak;Kim, Young Kyoon;Moon, Hwa Sik;Park, Sung Hak;Lee, Sang Yeub;In, Kwang Ho;Lee, Chang Youl;Kim, Young Sam;Kim, Hyung Jung;Ahn, Chul Min;Kim, Sung Kyu;Kim, Kyung Rok;Cha, Seung Ick;Jung, Tae Hoon;Kim, Mi Ok;Park, Sung Soo;Choi, Cheon Woong;Yoo, Jee Hong;Kang, Hong Mo;Koh, Won Jung;Ham, Hyoung Suk;Kang, Eun Hae;Kwon, O Jung;Lee, Yang Deok;Lee, Heung Bum;Lee, Yong Chul;Rhee, Yang Keun;Shin, Won Hyuk;Kwon, Sung Yeon;Kim, Woo Jin;Yoo, Chul Gyu;Kim, Young Whan;Shim, Young Soo;Han, Sung Koo;Park, Hye Kyung;Kim, Yun Seong;Lee, Min Ki;Park, Soon Kew;Kim, Mi Hye;Lee, Won Yeon;Yong, Suk Joong;Shin, Kye Chul;Choi, Byoung Whui;Oh, Yeon Mok;Lim, Chae Man;Lee, Sang Do;Kim, Woo Sung;Kim, Dong Soon;Jung, Sung Soo;Kim, Ju Ock;Ko, Young Chun
    • Tuberculosis and Respiratory Diseases
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    • v.58 no.5
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    • pp.498-506
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    • 2005
  • Background : This study compared the bronchodilator efficacy and safety of tiotropium inhalation capsules ($18{\mu}g$ once daily) with a ipratropium metered dose inhaler (2 puffs of $20{\mu}g$ q.i.d.) in patients with chronic obstructive pulmonary disease (COPD). Method : After the initial screening assessment and a two-week run-in period, patients received either tiotropium $18{\mu}g$ once daily or ipratropium $40{\mu}g$ four times daily over a period of 4 weeks in a double blind, double dummy, parallel group study. The outcome measures were the lung function, the daily records of the peak expiratory flow rate (PEFR), the patients' questionnaire, and the use of concomitant salbutamol. The forced expiratory volume in one second ($FEV_1$) and the forced vital capacity (FVC) were measured 5 minutes before inhalation, and 0.5, 1, 2 and 3 hours after inhaling the study drug on days 0, 14 and 28. Result : In 16 centers, 134 patients with a mean (SD) age of 66 (7) years and a predicted $FEV_1$ of 42 (12)% were analyzed. The trough $FEV_1$ response was significantly higher in the tiotropium group than in the ipratropium group after a four-week treatment period. The weekly mean morning PEFR of the tiotropium group was consistently higher than that of the ipratropium group during the 4-week treatment period with differences ranging from 12.52 to 13.88 l/min, which were statistically significant. Tiotropium was well tolerated by the COPD patients during the 4-week treatment period and had a similar safety profile to ipratropium. Conclusion : This study shows that tiotropium administrated once daily has a superior bronchodilator effect with a similar safety profile in treating COPD patients compared with ipratropium, inhaled four times daily.

Activation of NF-${\kappa}B$ in Lung Cancer Cell Lines in Basal and TNF-${\alpha}$ Stimulated States (폐암 세포에서 기저 상태와 TNF-${\alpha}$ 자극 시 NF-${\kappa}B$의 활성화)

  • HwangBo, Bin;Lee, Seung-Hee;Lee, Choon-Taek;Yoo, Chul-Gyu;Han, Sung-Koo;Shim, Young-Soo;Kim, Young-Whan
    • Tuberculosis and Respiratory Diseases
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    • v.52 no.5
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    • pp.485-496
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    • 2002
  • Background : The NF-${\kappa}B$ transcription factors control various biological processes including the immune response, acute phase reaction and cell cycle regulation. NF-${\kappa}B$ complexes are retained in the cytoplasm in the basal state and various stimuli cause a translocation of the NF-${\kappa}B$ complexes into the nucleus where they bind to the ${\kappa}B$ elements and regulate the transcription of the target genes. Recent reports also suggest that NF-${\kappa}B$ proteins are involved in oncogenesis, tumor growth and metastasis. High expression of NF-${\kappa}B$ expression was reported in many cancer cell lines and tissues. The constitutive activation of NF-${\kappa}B$ was also reported in several cancer cell lines supporting its role in cancer development and survival. The anti-apoptotic action of NF-${\kappa}B$ is important for cancer survival. NF-${\kappa}B$ also controls the expression of several proteins that are important for cellular adhesion (ICAM-1, VCAM-1) suggesting a role in cancer metastasis. In lung cancer, high expression levels of the NF-${\kappa}B$ subunit p50 and c-Rel were reported. In fact, high expression does not mean a high activity, and the activation pattern of NF-${\kappa}B$ in lung cancer has not been reported. Materials and Methods : In this study, the NF-${\kappa}B$ nuclear binding activity in the basal and TNF-${\alpha}$ stimulated states were exmined in various lung cancer cell lines and compared with the normal bronchial epithelial cell line. Twelve lung cancer cell lines including the non-small cell and small cell lung cancer cell lines (A549, NCI-H358, NCI-H441, NCI-H552, NCI-H2009, NCI-H460, NCI-H1229, NCI-H1703, NCI-H157, NCI-H187, NCI-H417, NCI-H526) and BEAS-2B bronchial epithelial cell line were used. To evaluate the NF-${\kappa}B$ expression and DNA binding activity, western blot analysis and an electrophoretic mobility shift assay with the nuclear protein extracts. Results : The basal expressions of the p65 and p50 subunits were observed in the BEAS-2B cell line and all lung cancer cell lines except for NCI-H358 and NCI-H460. The expression levels of p65 and p50 were increased 30 minutes after stimulation with TNF-${\alpha}$ in BEAS-2B and in 10 lung cancer cell lines. In the NCI-H358 and NCI-H460 cell lines, p65 expression was not observed in the basal and stimulated states and the two p50 related protein levels were higher after stimulation with TNF-${\alpha}$ These new proteins were smaller than p50 and are thought to be variants of p50. In the basal state, NF-${\kappa}B$ was nearly activated in the BEAS-2B and all lung cancer cell lines. The DNA binding activity of the NF-${\kappa}B$ complexes was markedly higher after stimulation with TNF-${\alpha}$ In the BEAS-2B and all lung cancer cell line except for NCI-H358 and NCI-H460, the activated NF-${\kappa}B$ complex was a p65/p50 heterodimer. In the NCI-H358 and NCI-H460 lung cancer cell lines, the NF-${\kappa}B$ complex was variant of a p50/p50 homodimer. Conclusion : The NF-${\kappa}B$ activation pattern in the lung cancer cell lines and the normal bronchial epithelial cell lines was similar except for the activation of a variant of the p50/p50 homodimer in some lung cancer cell linse.

Comparisons of Unicortical and Bicortical Lateral Mass Screws in the Cervical Spine : Safety vs Strength (경추부의 후관절 나사못 고정술에서 단피질삽입법과 양피질 삽입법 간의 특성에 관한 비교)

  • Park, Choon-Keun;Hwang, Jang-Hoe;Ji, Chul;Lee, Jae Un;Sung, Jae Hoon;Choi, Seung-Jin;Lee, Sang-Won;Seybold, Eric;Park, Sung-Chan;Cho, Kyung-Suok;Park, Chun-Kun;Kang, Joon-Ki
    • Journal of Korean Neurosurgical Society
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    • v.30 no.10
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    • pp.1210-1219
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    • 2001
  • Introduction : The purpose of this study was to analyze the safety, pullout strength and radiographic characteristics of unicortical and bicortical screws of cervical facet within cadaveric specimens and evaluate the influence of level of training on the positioning of these screws. Methods : Twenty-one cadavers, mean 78.9 years of age, underwent bilateral placement of 3.5mm AO lateral mass screw from C3-C6(n=168) using a slight variation of the Magerl technique. Intraoperative imaging was not used. The right side(unicortical) utilized only 14mm screws(effective length of 11mm) while on the left side to determine the length of the screw after the ventral cortex had been drilled. Three spine surgeons(attending, fellow, chief resident) with varying levels of spine training performed the procedure on seven cadavers each. All spines were harvested and lateral radiographs were taken. Individual cervical vertebrae were carefully dissected and then axial radiographs were taken. The screws were evaluated clinically and radiographically for their safety. Screws were graded clinically for their safety with respect to the spinal cord, facet joint, nerve root and vertebral artery. The grades consisted of the following categories : "satisfactory", "at risk" and "direct injury". Each screw was also graded according to its zone placement. Screw position was quantified by measuring a sagittal angle from the lateral radiograph and an axial angle from the axial radiograph. Pull-out force was determined for all screws using a material testing machine. Results : Dissection revealed that fifteen screws on the left side actually had only unicortical and not bicortical purchase as intended. The majority of screws(92.8%) were satisfactory in terms of safety. There were no injuries to the spinal cord. On the right side(unicortical), 98.9% of the screws were "satisfactory" and on the left side(bicortical) 68.1% were "satisfactory". There was a 5.8% incidence of direct arterial injury and a 17.4% incidence of direct nerve root injury with the bicortical screws. There were no "direct injuries" with the unicortical screws for the nerve root or vertebral artery. The unicortical screws had a 21.4% incidence of direct injury of the facet joint, while the bicortical screws had a 21.7% incidence. The majority of "direct injury" of bicortical screws were placed by the surgeon with the least experience. The performance of the resident surgeon was significantly different from the attending or fellow(p<0.05) in terms of safety of the nerve root and vertebral artery. The attending's performance was significantly better than the resident or fellow(p<0.05) in terms of safety of the facet joint. There was no relationship between the safety of a screw and its zone placement. The axial deviation angle measured $23.5{\pm}6.6$ degrees and $19.8{\pm}7.9$ degrees for the unicortical and bicortical screws, respectively. The resident surgeon had a significantly lower angle than the attending or fellow(p<0.05). The sagittal angle measured $66.3{\pm}7.0$ degrees and $62.3{\pm}7.9$ degrees for the unicortical and bicortical screws, respectively. The attending had a significantly lower sagittal angle than the fellow or resident(p<0.05). Thirty-three screws that entered the facet joint were tested for pull-out strength but excluded from the data because they were not lateral mass screws per-se and had deviated substantially from the intended final trajectory. The mean pull-out force for all screws was $542.9{\pm}296.6N$. There was no statistically significant difference between the pull-out force for unicortical($519.9{\pm}286.9N$) and bicortical($565.2{\pm}306N$) screws. There was no significant difference in pull-out strengths with respect to zone placement. Conclusion : It is our belief that the risk associated with bicortical purchase mandates formal spine training if it is to be done safely and accurately. Unicortical screws are safer regardless of level of training. It is apparent that 14mm lateral mass screws placed in a supero-lateral trajectory in the adult cervical spine provide an equivalent strength with a much lower risk of injury than the longer bicortical screws placed in a similar orientation.

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Effects of Total Mixed Fermentation Feeds Based on Rice-straw and Six Forage Crops on the Productivity of Holstein Cows (청예사료작물과 볏짚 위주의 완전배합발효사료 급여가 Holstein 착유우의 생산성에 미치는 영향)

  • Lee, H. J.;Kim, H. S.;Ki, K. S.;Jeong, H. Y.;Baek, K. S.;Kim, J. S.;Cho, K. K.;Cho, J. S.;Lee, H. G.;Woo, J. H.;Choi, Y. J.
    • Journal of Animal Science and Technology
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    • v.45 no.1
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    • pp.69-78
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    • 2003
  • This experiment was carried out to evaluate the value of total mixed fermentation feeds(TMFF) as completely mixed ration and to observe the effect of various kinds of TMFF on the palatability, feed intake, and milk performance in Holstein cows. The dry matter (DM) content of TMFF used in the experiment was 23.98-28.42% range, and CP, TDN, ADF and NDF were 16.2${\sim}$19.2%, 58.3-65.1%, 34.4-39.6% and 46.9${\sim}$49.9% levels, respectively. The relative feed value (RFV) in rape-, alfalfa-, grass-, oat-, corn-TMFF groups were 138.6, 133.9, 116.5, 111.8, 111.4 and 108.1, respectively. Among these groups, RFV of rye-TMFF group was lowest. Dry matter disappearance(DMD) showed 0.8${\sim}$.9% to the all kinds of TMFF groups. The pH was 3.89${\sim}$.87 and $NH_3$-N concentration was 6.93-8.66 mg/$d\ell$. The acetic acid concentration in the raw material of TMFF showed low level of 0.19${\sim}$0.57%, lactic acid showed high level of 1.17${\sim}$3.21% and butyric acid was very high as 0.03${\sim}$0.32%. Therefore, these results provide evidence that the quality of TMFF was not so bad. In the daily fresh matter intake on the alfalfa-, grass-, rape-, corn-, oats- and rye-TMFF were showed 62.85, 60.48, 58.04, 57.11, 54.61 and 45.74 kg respectively. All TMFF showed high palatability as daily dry matter intake of 1.95 to 2.90% by body weight of experimental cows. Body condition score(BCS) was gradually increased in during 60 days of the experiment term. Average daily gain(ADG) showed about 140.0${\sim}$326.7g. In alfalfa-TMFF group, the ADG was higher than in the other groups (p<0.05). Also, the increase in BCS was observed in grass-TMFF group (3.07 to 3.34) and rye-TMFF group was decreased in 3.07 to 3.34 (p<0.05). The milk yield appropriately showed a range of 16.16${\sim}$18.95 kg in all groups. Among these groups, alfalfa-TMFF group was highest(P<0.05). Average milk fat contents showed high levels of 4.06${\sim}$4.79% and the level was high in order of rape-, grass-, corn-, alfalfa-, rye- and oats-TMFF. Milk protein was highest in forage-TMFF and level of lactose in milk was approximately 4.56% in overall groups. Solid non fat(SNF) and total solid(TS) contents were 8.75% and 12.8%, respectively. However, milk composition was not significantly affected by TMFF.

The Effect of Nonspecific Endothelin-1 Receptor Blocker ($Bosentan^{(R)}$) on Paraquat Induced Pulmonary Fibrosis in Rat (Paraquat에 의한 백서의 폐섬유화증에서 비선택적 Endothelin-1 receptor blocker($Bosentan^{(R)}$)의 치료효과)

  • Jeong, Hye-Cheol;Jung, Ki-Hwan;Kim, Byung-Gyu;Lee, Seung-Heon;Kim, Min-Kyung;Kim, Chung-Yeul;Park, Sang-Myun;Lee, Sin-Hyung;Shin, Chol;Cho, Jae-Youn;Shim, Jae-Jeong;In, Kwang-Ho;Kim, Han-Gyum;Yoo, Se-Hwa;Kang, Kyung-Ho
    • 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.

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Studies on the Changes in Chemical Composition and Microbiological Aspects of Raw Milk by Microwave Heating (Microwave 열처리에 의한 원유의 화학적 및 미생물학적 성상의 변화에 관한 연구)

  • Shin, Byeong Hong;Kim, Jong Woo
    • Korean Journal of Agricultural Science
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    • v.25 no.2
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    • pp.181-198
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    • 1998
  • In order to determine the optimum pasteurization conditions by microwave heating(MWH) at $50^{\circ}C{\sim}70^{\circ}C$ for 30 minute compared with water bath heating(WBH) at $65^{\circ}C$ for 30minute during storage at $5^{\circ}C$, the chemical composition, microbiological changes and keeping quality were examined and the results were as follows: 1. The fat protein lactose, total solid contents of raw milk, at $50{\sim}70^{\circ}C$ for 30 min. in MWH and at 65 for $30^{\circ}C$ min. in WBH did not changed significantly during the storage at $5^{\circ}C$. 2. The pH and acidity for the raw milk untreated were 6.75 and 0.16%, and those of MWH heated and WBH milk wee 6.75~6.50 and 0.16%~0.19%, phosphatase test were negative at $61^{\circ}C$ for 20 min. at $62^{\circ}C$ for 15 min. at $63^{\circ}C$ for 10 min. at $64^{\circ}C$ for 5 min. at $65^{\circ}C$ for 5 min. in MWH and at $65^{\circ}C$ for 30 min. in WBH. 3. Whey protein content was $18.53mg/m{\ell}$ in raw milk untreated, however, those were decreased as the heating temperature increased. The proteolytic activity of treated milk by WBH(44%) was lower than that by MWH(94%). 4. Total bacteria counts were $2.8{\times}10^5CFU/m{\ell}$ in raw milk untreated, $2.8{\times}10^3CFU/m{\ell}$ at $65^{\circ}C$ for 30 min. $2.4{\times}10^3CFU/m{\ell}$ at $70^{\circ}C$ for 30 min. in MWH and $3.0{\times}10^3CFU/m{\ell}$ at $65^{\circ}C$ for 30 min. in WBH. Because total bacteria count did not increased in MWH at $65^{\circ}C$, $70^{\circ}C$ for 30 min. and $65^{\circ}C$ for 30 min. in WBH during the 10 days storaging, Also, total bacteria counts for treated milk were a most drastic decrease after $61^{\circ}C$, $62^{\circ}C$, $63^{\circ}C$, $64^{\circ}C$, $65^{\circ}C$ for 5 min. in MWH. 5. Coliform bacteria counts were $2.6{\times}10^3CFU/m{\ell}$ in raw milk untreated. There were not detected at $55^{\circ}C{\sim}70^{\circ}C$ for 30 min. in MWH and at $65^{\circ}C$ for 30 min. in WBH. Coliform bacteria counts were not detected after $61^{\circ}C$, $62^{\circ}C$, $63^{\circ}C$, $64^{\circ}C$, $65^{\circ}C$ for 5 min. in MWH. 6. Thermoduric bacteria counts were $5.2{\times}10^4CFU/m{\ell}$ in raw milk untreated, $2.0{\times}10^3CFU/m{\ell}$ at $65^{\circ}C$ for 30 min. $1.9{\times}10^3CFU/m{\ell}$ at $70^{\circ}C$ for 30min. in MWH and $2.2{\times}10^3CFU/m{\ell}$ at $65^{\circ}C$ for 30 min. in WBH. Because thermoduric bacteria counts did not increased in MWH at $65^{\circ}C$, $70^{\circ}C$ for 30 min. and $65^{\circ}C$ for 30 min. in WBH during the 10days storaging. Also, thermoduric bacteria counts were a most drastic decrease after $61^{\circ}C$, $62^{\circ}C$, $63^{\circ}C$, $64^{\circ}C$, $65^{\circ}C$ for 5 min. in MWH. 7. Psychrotrophic bacteria counts were $2.8{\times}10^5CFU/m{\ell}$ in raw milk untreated, $2.0{\times}10^1CFU/m{\ell}$ at $65^{\circ}C$ for 30 min. $2.0{\times}10^1CFU/m{\ell}$ at $70^{\circ}C$ for 30 min. in MWH and $3.0{\times}10^1CFU/m{\ell}$ at $65^{\circ}C$for 30 min. in WBH. Because psychrotrophic bacteria counts did not increased in MWH at $65^{\circ}C$, $70^{\circ}C$ for 30min. and $65^{\circ}C$ for 30 min. in WBH during the 10 days storaging. Also, psychrotrophic bacteria counts were a most drastic decrease after $61^{\circ}C$, $62^{\circ}C$, $63^{\circ}C$, $64^{\circ}C$, $65^{\circ}C$ for 5 min. in MWH.

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Internet Addiction in Adolescents and its Relation to Sleep and Depression (청소년의 인터넷 중독 : 수면, 우울과의 관련성)

  • Song, Ho-Kwang;Jeong, Mi-Hyang;Sung, Da-Jung;Jung, Jung-Kyung;Choi, Jin-Sook;Jang, Yong-Lee;Lee, Jin-Seong
    • Sleep Medicine and Psychophysiology
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    • v.17 no.2
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    • pp.100-108
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    • 2010
  • Objectives: "Internet-addiction" came into common use not only in clinical setting but also in everyday life. But, pathophysiology and diagnostic criteria of the internet addiction remain unknown. Because adolescents are in developing period, they might be vulnerable to the internet addiction, depression and sleep-related problem. The objectives of this study were to investigate the characteristics of internet addiction and its association with sleep pattern and depression in Korean adolescence. Methods: Subjects were 799 middle and high school students in Seoul, Korea. We administered a self-reported questionnaire including socio-demographic data, Korean versions of Young's Internet Addiction Scale (YIAS), Pittsburgh Sleep Quality Index (PS-QI), the Center for Epidemiologic Studies for Depression Scale (CES-D) and questions about internet using patterns. Data of 696 subjects were included in analysis. Chi-square tests were used to analyze proportional differences, and ANOVA with post-hoc tests were used to analyze differences among groups. Partial correlation analyses were performed to analyze the correlation of internet addiction with other variables (two-tailed, p<0.05). Results: Of the 696 participants (grade 2 of middle school; M2 135 vs. grade 1 of high school; H1 238 vs. grade 2 of high school; H2 323), 2.0% (n=14) were internet-addicted (IA), 27.7% (n=193) were over-using (OU) and 70.3% (n=489) were not-addicted (NA). The mean scores of YIAS, PSQI and CES-D scores were 35.24${\pm}$12.78, 5.53${\pm}$3.04 and 16.72${\pm}$8.69, respectively. In higher grade students, average total sleep time was shorter (M2 426.20${\pm}$67.68 min. vs. H1 380.47${\pm}$62.57 min. vs. H2 354.67${\pm}$73.37 min., F=51.909, p<0.001), and PSQI (4.69${\pm}$3.14 vs. 5.42${\pm}$3.15 vs. 5.97${\pm}$2.83, F=8.871, p<0.001) CES-D (13.53${\pm}$8.37 vs. 16.96${\pm}$8.24 vs. 17.87${\pm}$8.84, F=12.373, p<0.001) scores were higher than those of lower grade students. Comparing variables among IA, OU and NA groups, computer using time not for study (96.36${\pm}$63.31 min. vs. 134.92${\pm}$86.79 min. vs. 213.57${\pm}$136.87 min., F=34.287, p<0.001) and portable device using time not for study (84.22${\pm}$79.11 min. vs. 96.97${\pm}$91.89 min. vs. 152.31${\pm}$93.64 min., F= 5.400, p=0.005) were different among groups. PSQI (5.26${\pm}$2.97 vs. 6.08${\pm}$2.97 vs. 7.50${\pm}$4.41, F=8.218, p<0.001) and CES-D scores (15.40${\pm}$8.08 vs. 19.05${\pm}$8.42 vs. 30.43${\pm}$13.69, F=32.692, p<0.001) were also different among groups. YIAS score were correlated with computer using time not for study (r=0.356, p<0.001) and portable device using time not for study (r= 0.136, p<0.001). PSQI score (r=0.237, p<0.001) and CES-D score (r=0.332, p<0.001). YIAS score and PSQI score (r=0.131, p= 0.001), YIAS and CES-D score (r=0.265, p<0.001), PSQI score and CES-D score (r=0.357, p<0.001) were correlated each other. Conclusion: These results suggested that adolescents' internet-addiction was correlated with not only computer and portable device using time not for study but also depression and sleep-related problems. We should pay attention to depression and sleep-related problems, when evaluating internet-addiction in adolescents.

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