• Title/Summary/Keyword: Lung deposition

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Searching for Novel Candidate Small Molecules for Ameliorating Idiopathic Pulmonary Fibrosis: a Narrative Review

  • Kyung-il Kim;Rajib Hossain;Xin Li;Hyun Jae Lee;Choong Jae Lee
    • Biomolecules & Therapeutics
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    • v.31 no.5
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    • pp.484-495
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    • 2023
  • Idiopathic pulmonary fibrosis (IPF) can be defined as a progressive chronic pulmonary disease showing scarring in the lung parenchyma, thereby resulting in increase in mortality and decrease in the quality of life. The pathophysiologic mechanism of fibrosis in IPF is still unclear. Repetitive microinjuries to alveolar epithelium with genetical predisposition and an abnormal restorative reaction accompanied by excessive deposition of collagens are involved in the pathogenesis. Although the two FDA-approved drugs, pirfenidone and nintedanib, are under use for retarding the decline in lung function of patients suffered from IPF, they are not able to improve the survival rate or quality of life. Therefore, a novel therapeutic agent acting on the major steps of the pathogenesis of disease and/or, at least, managing the clinical symptoms of IPF should be developed for the effective regulation of this incurable disease. In the present review, we tried to find a potential of managing the clinical symptoms of IPF by natural products derived from medicinal plants used for controlling the pulmonary inflammatory diseases in traditional Asian medicine. A multitude of natural products have been reported to exert an antifibrotic effect in vitro and in vivo through acting on the epithelial-mesenchymal transition pathway, transforming growth factor (TGF)- β-induced intracellular signaling, and the deposition of extracellular matrix. However, clinical antifibrotic efficacy of these natural products on IPF have not been elucidated yet. Thus, those effects should be proven by further examinations including the randomized clinical trials, in order to develop the ideal and optimal candidate for the therapeutics of IPF.

The Role of Transglutaminase-2 in Fibroproliferation after Lipopolysaccharide-induced Acute Lung Injury (리포다당질로 유도된 급성 폐손상 후 섬유화증식에서 Transglutaminase-2의 역할)

  • Kim, Je-Hyeong
    • Tuberculosis and Respiratory Diseases
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    • v.69 no.5
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    • pp.337-347
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    • 2010
  • Background: Transglutaminase-2 (TG-2) has been reported to play an important role in the process of fibrosis. However, TG-2 studies on fibroproliferation of acute lung injury (ALI) are absent. The purpose of this study was to investigate the role of TG-2 in the fibroproliferation of lipopolysaccharide (LPS)-induced ALI. Methods: The male C57BL/6 mice of 5 weeks age were divided into 3 groups; control group (n=30) in which $50{\mu}L$ of saline was given intratracheally (IT), LPS group (n=30) in which LPS 0.5 mg/kg/$50{\mu}L$ of saline was given IT, and LPS+Cyst group treated with intraperitoneal 200 mg/kg of cystamine, competitive inhibitor of TG-2, after induction of ALI by LPS. TG-2 activity and nuclear factor $(NF)-{\kappa}B$ were measured in lung tissue homogenate. Tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-$1{\beta}$, IL-6, myeloperoxidase (MPO), and transforming growth factor (TGF)-${\beta}1$ were measured using bronchoalveolar lavage fluids. Histopathologic ALI score and Mallory's phosphotunistic acid hematoxylin (PTAH) for collagen and fibronectin deposition were performed. Results: The TG-2 activities in the LPS group were significantly higher than the control and LPS+Cyst groups (p<0.05). The TNF-${\alpha}$ and IL-$1{\beta}$ concentrations and $NF-{\kappa}B$ activity were lower in the LPS+Cyst group than the LPS group (p<0.05). The LPS+Cyst group showed lower MPO, ALI score, TGF-${\beta}1$ concentration, and Mallory's PTAH stain than the LPS group, but the differences were not significant (p>0.05). Conclusion: Inhibition of TG-2 activity in the LPS-induced ALI prevented early inflammatory parameters, but had limited effects on late ALI and fibroproliferative parameters.

Study on the Regional Deposition of Smoke Particles in Human Respiratory Tract under the Variation of Fire and Breathing Conditions (화재 및 호흡조건 변화에 따른 연기입자의 인체 호흡기 내 영역별 침착량 분석)

  • Goo, Jaehark
    • Fire Science and Engineering
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    • v.33 no.6
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    • pp.95-104
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    • 2019
  • Smoke generated in a fire consists of gaseous substances and particulate matter, such as unburned carbon that adsorbed the gases. Human injury caused by inhalation of gaseous substances present in smoke is mostly short-term, whereas damage caused by inhalation of particulate matter is relatively a long-term phenomenon depending on the state of the gas-phase adsorption. The amount and location of the deposited smoke particles are important factors in estimating the damage caused to humans, which are affected by the breathing conditions as well as particle conditions, such as the size and concentration affected by the combustion conditions. In this study, in order to understand the characteristics of the deposition of smoke particles in the respiratory tract related to the study of human smoke inhalation injury, the number and mass concentration of smoke particles deposited in different areas of the respiratory tract for different fuel types, combustion conditions and breathing conditions were calculated. In addition, the amount of mass deposition of smoke in the respiratory tract for a certain period of inhalation was compared with the atmospheric standard of fine dust.

Potential Biases Arising in the Use of Cascade Impactors to Estimate Respiratory Tract Deposition Patterns of Lead-Acid Battery Plant Aerosols

  • Hodgkins Douglas G.;Robins Thomas G.;Hinkamp David L.;Levine Steven P.;Schork M. Anthony;Krebs William H.
    • 대한예방의학회:학술대회논문집
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    • 1994.02a
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    • pp.585-595
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    • 1994
  • The region of the respiratory tract where inhaled particles deposit can have important implications for the causation of local or systemic toxic effects. For most aerosols of occupational importance, respiratory tract deposition can be predicted from the aerodynamic diameter of the particles. With the advent of cascade impactors, particularly those of personal sampler size, the determination of the aerodynamic diameters of aerosols has become more common. Some limitations of cascade impactor use are well recognized (e.g., particle bounce and substrate overloading) and are generally correctable. However, two important limitations of the instruments may not be receiving adequate attention: relative humidity effects on potentially hygroscopic aerosols and the collection characteristics of fibrous aerosols as compared to their actual deposition site potential. The results of this study, when compared to results of previous controlled laboratory trials, suggest that, while potentially hygroscopic lead aerosols from lead acid battery plant operations do not appear to be affected by changes in plant environmental humidity levels, the potential - exists for significant size changes upon inhalation. Secondly, fibers were detected in aerodynamic size ranges that would be associated with deep lung deposition; however, upon microscopic examination, these same fibers would actually be predicted to deposit in the upper airways. This study suggests that the physicalchemical properties and morphological features of an aerosol should be carefully considered by industrial hygienists before cascade impactors are used in attempts to predict the effects of inhaled aerosols.

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Daily Concentration Measurements of Water-soluble Inorganic Ions in the Atmospheric Fine Particulate for Respiratory Deposition Region (호흡기 침착부위에 따른 미세먼지 중 수용성 이온성분의 일별 농도 측정)

  • Kang, Gong-Unn;Lee, Sang-Bok
    • Journal of Environmental Health Sciences
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    • v.31 no.5 s.86
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    • pp.387-397
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    • 2005
  • In oder to understand the deposition possibility of water-soluble inorganic ions in the atmospheric fine particulates for the human respiratory tract, the mass size distribution of ion species was measured using an Anderson sampler in the Iksan during fall, 2004. Samples were analyzed for major water-soluble ions using Dionex DX-100 ion chromatograph. The size distribution of water-soluble inorganic ions in the atmospheric particulates appeared bimodal distribution, which were divided around $1-2{\mu}m$ into two groups. Mass site distribution of total ion in the coarse mode was found to be almost similar level during the sampling period, but fluctuations of mass size distribution in the fine mode were observed. Considering the mass size distribution of total ion concentrations for the respiratory deposition region, it was found that about 77.1% of total tons could be deposited in the alveolar region, and which dominated the daily variation of total ion concentrations. The concentration of total ions, which could be deposited in both the head region and the tracheobronchial region, was $3.95{\mu}g/m^3$, whereas that in the alveolar rerion was $13.28{\mu}g/m^3$. Dominant ions which could be deposited in the alveolar region were ${NO_3}{^-},\;{SO_4}^{2-}\;and\;{NH_4{^+}$, accounting for about 40%, 27% and 22% of the total ions, respectively. Although $K^+$ was approximately 3% of total ions, it was shown that most of this could be deposited in the alveolar region due to its high fraction of small size distribution originated from anthropogenic source of biomass burning. The presence of these ions in the fine mode may be of public health significance as they are very biologically harmful to health and have a high probability of being deposited in human lung tissue.

Histomorphologic Change of Radiation Pneumonitis in Rat Lungs : Captopril Reduces Rat Lung Injury Induced by Irradiation (X-선 조사로 생긴 흰쥐 폐장 상해의 형태학적 변화: Captopril에 의한 폐장 상해의 경감 효과)

  • Kim, Jin-Hee
    • Radiation Oncology Journal
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    • v.17 no.3
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    • pp.238-248
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    • 1999
  • Purpose : To assess the histomorphologic changes in the rat lung injury induced by radiation, to determine whether captopril reduces the rat lung injury and to evaluate change in TNF-${\alpha}$ and TGF-${\beta}$ in rat lung damage by radiation and captopril Methods and material : Right lungs in male Sprague-Dawley rats were divided irradiation alone (10, 20, 30 Gy) or radiation (same dose with radiation alone group) with captopril (500 mg/L). Radiation alone group were sacrificed at twelve hours and eleven weeks after radiation and radiation with captopril group (captopril group) were sacrificed at eleven weeks after radiation with captopril. We examined the light microscope and electron microscopic features in the groups. Results : In radiation alone group, there were patch parenchymal collapse and consolidation at twelve hours after radiation. The increase of radiation dose shows more prominent the severity and broader the affected areas. Eleven weeks after radiation, the severity and areas of fibrosis had increased in proportion to radiation dose given in the radiation alone group. There was notable decrease of lung fibrosis in captopril group than in radiation alone group. The number of mast cells rapidly increased with increase of radiation dose in radiation alone group and the degree of increase of mast cell number and severity of collagen accumulation more decreased in captopril group than in radiation alone group. In radiation alone group, expression of TNF-${\alpha}$ and TGF-${\beta}$ increased according to increase of radiation dose at twelve hours after radiation in both group. At eleven weeks after radiation, expression of TGF-${\beta}$ increased according to increase of radiation dose in radiation group but somewhat decreased in captopril group. In the captopril group the collagen deposition increased but less dense than those of radiation alone group. The severity of perivascular thickening, capillary change, the number and degranulation of mast cells more decreased in the captopril group than in the radiation alone group. Conclusion : It is concluded that the effect of captopril in the rat lungs after radiation was considered to be due to its effect on inhibition of mast cells and reduction of collagen deposition, and captopril may be protect in lung damage after radiation. We observed expression of TNF-${\alpha}$ and TGF-${\beta}$ increased at the early phase after radiation and expression of TGF-${\beta}$ increased in proportion to increase of radiation dose at the chronic phase after radiation. This results will contribute to future investigation in reduction mechanism of captopril in lung damage after radiation.

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Effects of Kumsooyukkun-jeon on Asthma Induced by Ovalbumin in Mice (금수육군전이 Ovalbumin으로 수발된 Mice의 천식에 미치는 영향)

  • 김춘석;최해윤;김종대
    • The Journal of Korean Medicine
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    • v.23 no.3
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    • pp.104-118
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    • 2002
  • Objectives : To study the effects of Kumsooyukkun-jeon on asthma. Methods : Asthma was induced to Balb/c mice with ovalbumin using the method of Hatfield et al. We measured the histological profiles of lung and trachea, numbers of cellular compartments in the bronchoalveolar lavage fluid (BALF), numbers and morphology of the mast cells in the trachea, numbers of mucous-secretory cells in the bronchus, morphology of the bronchus, ultramicroscopical appearance of surface of trachea and number of cilia and mucous-secretory cells by scanning electron microscope. Results : 1. Hypertrophy of mucous membrane of trachea and bronchus and bronchioles in the lung, peritracheal, peribronchus and peribronchiolar inflammatory cell infiltration, and mucoid exudate deposition the lumen were observed in control groups but these phenomena were recovered in the Kumsooyukkun-jeon groups. 2. Cellular compartments including neutrophil and eosinophil were increased in the BALF of control groups but these phenomena were recovered in the Kumsooyukkun-jeon groups. 3. Degranulation and decrease of the numbers of mast cells were detected in the trachea of control groups. However, these phenomena were recovered in the Kumsooyukkun-jeon groups. 4. Shedding, decrease of cilia cell and increase of mucous-secretory cells in the surface of the trachea were measured in control groups but these phenomena were recovered in the Kumsooyukkun-jeon groups. Conclusions : It is considered that Kumsooyukkun-jeon has somewhat favorable effects on asthma.

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Therapeutic Use of Stem Cell Transplantation for Cell Replacement or Cytoprotective Effect of Microvesicle Released from Mesenchymal Stem Cell

  • Choi, Moonhwan;Ban, Taehyun;Rhim, Taiyoun
    • Molecules and Cells
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    • v.37 no.2
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    • pp.133-139
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    • 2014
  • Idiopathic pulmonary fibrosis (IPF) is the most common and severe type of idiopathic interstitial pneumonias (IIP), and which is currently no method was developed to restore normal structure and function. There are several reports on therapeutic effects of adult stem cell transplantations in animal models of pulmonary fibrosis. However, little is known about how mesenchymal stem cell (MSC) can repair the IPF. In this study, we try to provide the evidence to show that transplanted mesenchymal stem cells directly replace fibrosis with normal lung cells using IPF model mice. As results, transplanted MSC successfully integrated and differentiated into type II lung cell which express surfactant protein. In the other hand, we examine the therapeutic effects of microvesicle treatment, which were released from mesenchymal stem cells. Though the therapeutic effects of MV treatment is less than that of MSC treatment, MV treat-ment meaningfully reduced the symptom of IPF, such as collagen deposition and inflammation. These data suggest that stem cell transplantation may be an effective strategy for the treatment of pulmonary fibrosis via replacement and cytoprotective effect of microvesicle released from MSCs.

A Case of Henoch-Schönlein Purpura Developed during Treatment of Lung Cancer (원발성 폐암 치료 중 발생한 Henoch-Schönlein Purpura 1예)

  • Kang, Min Soo;Noh, Geum Yeub;Jang, Young Joo;Cho, Soo Youn;Rhim, Kyung Jin;Noh, Hee Sun;Kim, Hye-Ryoun;Kim, Cheol Hyeon;Lee, Jae Cheol
    • Tuberculosis and Respiratory Diseases
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    • v.67 no.3
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    • pp.234-238
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    • 2009
  • Henoch-$Sch\ddot{o}nlein$ Purpura (HSP) is a systemic vasculitis involving small vessels with the deposition of immune complexes containing IgA and C3, which is characterized by associated skin, joint, renal, and gastrointestinal manifestations. Although there were several causes such as autoimmunity, infection, and drugs, it also can be presented as a form of vasculitidies associated with malignancies. We report a case of HSP developed during treatment for non-small cell lung cancer in a 66-year-old man. Multiple purpuric skin lesions occurred in both legs after the first cycle of chemotherapy, which was diagnosed as HSP by clinical and pathologic examinations. Due to the itching sensation, topical steroid was applied and the patient was improved 3 weeks later without a scheduled change in chemotherapy.