• Biomolecules & Therapeutics
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• 제28권3호
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• pp.250-258
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• 2020

Emphysema, a major component of chronic obstructive pulmonary disease (COPD), is a leading cause of human death worldwide. The progressive deterioration of lung function that occurs in the disease is caused by chronic inflammation of the airway and destruction of the lung parenchyma. Despite the main impact of inflammation on the pathogenesis of emphysema, current therapeutic regimens mainly offer symptomatic relief and preservation of lung function with little therapeutic impact. In the present study, we aimed to discover novel therapeutics that suppress the pathogenesis of emphysema. Here, we show that LJ-2698, a novel and highly selective antagonist of the adenosine A₃ receptor, a G protein-coupled receptor involved in various inflammatory diseases, significantly reversed the elastase-induced destructive changes in murine lungs. We found that LJ-2698 significantly prevented elastase-induced airspace enlargement, resulting in restoration of pulmonary function without causing any obvious changes in body weight in mice. LJ-2698 was found to inhibit matrix metalloproteinase activity and pulmonary cell apoptosis in the murine lung. LJ-2698 treatment induced increases in anti-inflammatory cytokines in macrophages at doses that displayed no significant cytotoxicity in normal cell lines derived from various organs. Treatment with LJ-2698 significantly increased the number of anti-inflammatory M2 macrophages in the lungs. These results implicate the adenosine A₃ receptor in the pathogenesis of emphysema. Our findings also demonstrate the potential of LJ-2698 as a novel therapeutic/preventive agent in suppressing disease development with limited toxicity.

• Tuberculosis and Respiratory Diseases
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• 제85권1호
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• pp.18-24
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• 2022

Background: Neutrophilic asthma (NeuA) is usually resistant to corticosteroids. Tiotropium bromide (TIO) is a bronchodilator that is used as an add-on therapy to inhaled corticosteroid and long-acting β2 agonist in asthma treatment. However, the role of TIO in NeuA is not fully known. Thus, the aim of this study was to evaluate the effect of TIO on NeuA compared to that of corticosteroids. Methods: C57BL/6 female mice were sensitized with ovalbumin and lipopolysaccharide to induce neutrophilic inflammation. Dexamethasone (DEX) was administered on days 14, 17, 20, and 23. TIO was inhaled on days 21, 21, and 23. On day 24, mice were sacrificed. Airway hyper-responsiveness, levels of cytokines in bronchoalveolar lavage (BAL) and lung homogenates, and lung tissue histopathology were compared between the two groups. Results: Neutrophil counts, T helper 2 cells (T_H2)/T_H17 cytokines, and pro-inflammatory cytokine in BAL fluids were elevated in the NeuA group. TIO group showed lower total cells, neutrophil counts, and eosinophil counts in BAL fluids than the DEX group (p<0.001, p<0.05, and p<0.001, respectively). Airway resistance was attenuated in the TIO group but elevated in the NeuA group (p<0.001). Total protein, interleukin (IL)-5, and IL-17A levels in BAL fluids were lower in the TIO group than in the NeuA group (all p<0.05). Conclusion: TIO showed more potent effects than DEX in improving airway inflammation and attenuating airway resistance in NeuA.

• Toxicological Research
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• 제30권2호
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• pp.83-90
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• 2014

An increasing number of recent studies have focused on the impact of particulate matter on human health. As a model for atmospheric particulate inhalation, we investigated the effects of inhaled carbon black nanoparticles (CBNP) on mice with bleomycin-induced pulmonary fibrosis. The CNBPs were generated by a novel aerosolization process, and the mice were exposed to the aerosol for 4 hours. We found that CBNP inhalation exacerbated lung inflammation, as evidenced by histopathology analysis and by the expression levels of interleukin-6 protein, fibronectin, and interferon-${\gamma}$ mRNAs in lung tissues. Notably, fibronectin mRNA expression showed a statistically significant increase in expression after CBNP exposure. These data suggest that the concentration of CBNPs delivered (calculated to be $12.5{\mu}g/m^3$) can aggravate lung inflammation in mice. Our results also suggest that the inhalation of ultrafine particles like PM 2.5 is an impactful environmental risk factor for humans, particularly in susceptible populations with predisposing lung conditions.

• 한국임상수의학회지
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• 제26권1호
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• pp.72-75
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• 2009

Pulmonary bullae are air-filled spaces within the lung parenchyma that result from the destruction, dilatation and confluence of adjacent alveoli. Pulmonary bullae are found most often in healthy, middle aged, large breed or deep-chested dogs that have no previous history of lung disease and bulla may occur as a result of emphysema, inflammation or trauma. Clinical signs include respiratory distress, anorexia, depression and tachypnea. In this study, a dog with respiratory distress by traffic accident was diagnosed as pulmonary bullae with pneumothorax using radiography at Veterinary Medical Teaching Hospital, GNU. In radiographs, various sized, smooth margin, well defined, oval shaped, gas or fluid filled multiple bullae are shown in the left cranial, left caudal and right accessory lobes. At the initial stage of observation, there were indications of four bullae, two of which were not found in the following radiograph. At the same time, there were serious indications of lung consolidation that caused respiratory distress of patient. Ultimately, the patient was expired after ten hours.

• Tuberculosis and Respiratory Diseases
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• 제74권1호
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• pp.7-14
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• 2013

Background: Fractional exhaled nitric oxide (FeNO) can be measured easily, rapidly, and noninvasively for the assessment of airway inflammation, particularly mediated by eosinophil, such as asthma. In bronchiectasis (BE), the pathogenesis has been known as chronic airway inflammation and infection with abnormal airway dilatation; however, there are little studies to evaluate the role of FeNO in BE. Methods: From March 2010 to February 2012, 47 patients with BE, diagnosed by high resolution computed tomography (HRCT), performed FeNO, compared with asthma and chronic obstructive pulmonary disease (COPD). All patients carried out a complete blood count including eosinophil count, chemistry, sputum examination, and spirometry, if indicated. A retrospective analysis was performed to elucidate the clinical role of FeNO in BE patients. Results: The mean FeNO levels in patients with BE was $18.8{\pm}1.5$ part per billion (ppb), compared to $48.0{\pm}6.4$ and $31.0{\pm}4.3$ in those with asthma and COPD, respectively (p<0.001). The FeNO levels tended to increase along with the disease severity scores by HRCT; however, it was statistically not significant. FeNO in BE with a co-infection of nontuberculous mycobacteria was the lowest at $17.0{\pm}3.5$ ppb among the study population. Conclusion: FeNO in BE was lower than other chronic inflammatory airway diseases, particularly compared with asthma. For clinical application of FeNO in BE, more large-scaled, prospective studies should be considered.

• Tuberculosis and Respiratory Diseases
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• 제42권5호
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• pp.767-771
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• 1995

저자등은 객혈을 주소로 내원한 기관지동맥과 폐정맥의 동정맥기형 1예를 기관지동맥 조영술로 확진하고 치료하였기에 문헌고찰과 함께 보고하는 바이다.

• Toxicological Research
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• 제26권2호
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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.

• Journal of Korean Neurosurgical Society
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• 제37권2호
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• pp.146-149
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• 2005

Most primary spinal abscesses, irrespective of pathogens and anatomical locations, have better prognosis than that of secondary abscesses with spondylitis. We report a 68-year-old man, previously undertaken pulmonary resection due to tuberculosis, presented with paraparesis. Imaging studies showed primary intraspinal abscesses at T-1 and T-3 vertebral levels, semi-invasive pulmonary Aspergillosis and inflammation of the posterior mediastinum. Operative procedure and histopathological examination revealed interdural Aspergillus abscess. Despite chemotherapy, he deteriorated progressively, and spondylitis developed at corresponding vertebrae. He eventually died 6 weeks postoperatively due to pulmonary complication. The authors intended to inform that such an extradural inflammatory lesion of Aspergillus abscess should be treated carefully.

• 한국임상수의학회지
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• 제19권2호
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• pp.250-252
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• 2002

A 14-year-old female Gill's bottle-nosed dolphin died after having 1 month history of depression, anorexia, and respiratory insufficiency. At necropsy, numerous well-demarcated tan firm nodules in variable sizes ranging from 2 m to 3 cm in diameter were scattered throughout the lung lobes. Histologically, the pulmonary nodules formed typical granulomatous inflammation. Center of the granulomatous foci consisted of necrotic center with gram positive cocci surrounded by eosinophilic Splendore-Hoeppli material then by macrophages, epithelioid cells, multinucleated giant cells, a few lymphocytes and fibroblasts. The is the first report of pulmonary botryomycosis in dolphin in Korea.

• 환경위생공학
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• 제3권1호
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• pp.1-8
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• 1988

It has been reported that the pulmonary mycosis generally results from saprophytic colonization of pre-existing lung cavities usually due to pulmonary tuberculosis etc. Culture of homogenized tissues yield pure colony of slightly brown on the Sabouraud dextrose medium. The fungus was identified as the Scophulariopsis brevieaulis which had been rarely reported in pulmonary fungal infection. Histopathological examination of excised tissues revealed a chronic granulomatous inflammation and many branched hyphal mass. Susceptibility tests were tested with ketoconazole, griseofulvin, nystatin, and amphotericin B. Of these antifungal agents, ketoconazole and griseofulvin proved to be most effective and minimum inhibitory concentration was $10{\mu}g/ml,\;50 {\mu}g/ml$, respectively.