• Toxicological Research
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• v.28 no.1
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• pp.25-31
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• 2012

The purpose of this study was to determine the acute pulmonary toxicity of metallic silver nanoparticles (MSNPs, 20.30 nm in diameter). Acute pulmonary toxicity and body distribution of inhaled MSNPs in mice were evaluated using a nose-only exposure chamber (NOEC) system. Bronchoalveolar lavage (BAL) fluid analysis, Western blotting, histopathological changes, and silver burdens in various organs were determined in mice. Mice were exposed to MSNPs for 6 hrs. The mean concentration, total surface area, volume and mass concentrations in the NOEC were maintained at $1.93{\times}10^7$ particles/$cm^3$, $1.09{\times}10^{10}\;nm^2/cm^3$, $2.72{\times}10^{11}\;nm^3/cm^3$, and 2854.62 ${\mu}g/m^3$, respectively. Inhalation of MSPNs caused mild pulmonary toxicity with distribution of silver in various organs but the silver burdens decreased rapidly at 24-hrs post-exposure in the lung. Furthermore, inhaled MSNPs induced activation of mitogen-activated protein kinase (MAPK) signaling in the lung. In summary, single inhaled MSNPs caused mild pulmonary toxicity, which was associated with activated MAPK signaling. Taken together, our results suggest that the inhalation toxicity of MSNPs should be carefully considered at the molecular level.

• Tuberculosis and Respiratory Diseases
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• v.58 no.1
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• pp.78-82
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• 2005

Propylthiouracil(PUT) is a drug which used at Grave's disease. But PTU has recently been observed to associated with antineutrophil cytoplasmic antibody(ANCA)-positive vasculitis resulting in, infrequently, diffuse alveolar hemorrhage. We report the case of a patient who developed diffuse pulmonary hemorrhage after she had been taking PTU for two years. She had received a diagnosis of Grave's disease at two years ago. The serologic study was positive for ANCA with myeloperoxidase(MPO) specificity. Bronchoalveloar lavage(BAL) fluid analysis revealed hemosiderinladen macrophages. Such findings suggested propylthiouracil-induced dffuse pulmonary hemorrhage associated with antineutrophil cytoplasmic antibody. To our knowledge, this represents the first documentation in a case of PTU-induced diffuse pulmonary hemorrhage in Korea.

• Tuberculosis and Respiratory Diseases
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• v.47 no.6
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• pp.843-849
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• 1999

The prevalence of nonspecific interstitial pneumonitis(NSIP) in HIV-positive patients with pulmonary disease has varied from 11 to 38%. But NSIP in HIV-positive patients is indistinguishable from Pneumocystis carinii pneumonia(PCP) clinically and radiologically. The number of HIV-positive patients is less in Korea than in western developed countries, so little attention has been paid to the differential diagnosis between NSIP and PCP. We report a case of NSIP in HIV-positive, 61-year-old man which mimicked PCP. He presented with cough, sputum and mild exertional dyspnea. Lung sound was clear. But, chest X-ray and HRCT demonstrated diffuse patch and bilateral ground-glass opacities in central and perihilar area of both lung. Microbial pathogens were not found on sputum, BAL fluid and tissues taken by TBLB. In transbronchial lung biopsy specimen, interstitial infiltrates with lymphocytes were distributed on peribronchiolar regions. A pathologic diagnosis of NSIP was suggested, he received symptomatic treatment. The follow-up chest X-ray showed near complete resolution.

• Tuberculosis and Respiratory Diseases
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• v.63 no.2
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• pp.145-153
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• 2007

Background: Asthma is a syndrome that is characterized by a variable degree of airflow obstruction, bronchial hyperresponsiveness, and airway inflammation. Colchicine is an inexpensive and safe medication with unique anti-inflammatory properties. IL-1Ra (Interleukin-1 receptor antagonist) mediates the anti-inflammatory effect in human inflammatory diseases, including asthma. This study examined whether IL-1Ra mediates the anti-inflammatory effect of colchicine in normal human bronchial epithelial cells (NHBE), RAW 264.7 cells (murine macrophage cell line), and a mouse lung. Methods: NHBE, RAW 264.7 cells and BALB/c mice were stimulated with colchicine, and the increase in the IL-1Ra level was estimated by ELISA, Western analysis and RT-PCR analysis. Results: Colchicine stimulated NHBE and RAW 264.7 cells to release IL-1Ra into the supernatant in a dose-and time-dependent manner. The major isoform of IL-1Ra in NHBE and RAW 264.7 cells is type I icIL-1Ra, and sIL-1Ra, respectively. IL-1Ra up-regulation was blocked by PD98059, a specific inhibitor in MAPK pathways. Colchicine also stimulated the secretion of IL-1Ra into the bronchoalveolar lavage (BAL) fluid of BALB/c mouse. Conclusion: Colchicine stimulates an increase in the IL-1Ra level both in vivo and in vitro, and might have an anti-inflammatory effect.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.1
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• pp.65-71
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• 2015

Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness (AHR) and reversible airway obstruction. Methacholine (MCh) is widely used in broncho-provocation test to evaluate airway resistance. For experimental investigation, ovalbumin-induced sensitization is frequently used in rodents (Ova-asthma). However, albeit the inflammatory histology and AHR in vivo, it remains unclear whether the MCh sensitivity of airway smooth muscle isolated from Ova-asthma is persistently changed. In this study, the contractions of airways in precision-cut lung slices (PCLS) from control, Ova-asthma, and IL-13 overexpressed transgenic mice (IL-13TG) were compared by analyzing the airway lumen space (AW). The airway resistance in vivo was measured using plethysmograph. AHR and increased inflammatory cells in BAL fluid were confirmed in Ova-asthma and IL-13TG mice. In the PCLS from all three groups, MCh concentration-dependent narrowing of airway lumen (${\Delta}AW$) was observed. In contrast to the AHR in vivo, the $EC_{50}$ of MCh for ${\Delta}AW$ from Ova-asthma and IL-13TG were not different from control, indicating unchanged sensitivity to MCh. Although the AW recovery upon MCh-washout showed sluggish tendency in Ova-asthma, the change was also statistically insignificant. Membrane depolarization-induced ${\Delta}AW$ by 60 mM $K^+$ (60K-contraction) was larger in IL-13TG than control, whereas 60K-contraction of Ova-asthma was unaffected. Furthermore, serotonin-induced ${\Delta}AW$ of Ova-asthma was smaller than control and IL-13TG. Taken together, the AHR in Ova-asthma and IL-13TG are not reflected in the contractility of isolated airways from PCLS. The AHR of the model animals seems to require intrinsic agonists or inflammatory microenvironment that is washable during tissue preparation.

• Microbiology and Biotechnology Letters
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• v.50 no.4
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• pp.574-583
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• 2022

Ficus vasculosa Wall. ex Miq. (FV) has been used as a herbal medicine in Southeast Asia and its antioxidant activity has been shown in previous studies. However, it has not yet been elucidated whether FV exerts anti-inflammatory effects on activated-macrophages. Thus, we aimed to evaluate the ameliorative property of FV methanol extract (FM) on lipopolysaccharide (LPS)-induced inflammatory responses and the underlying molecular mechanisms in RAW264.7 macrophages. The experimental results indicated that FM decreased the production of inflammatory mediators (NO/PGE2) and the mRNA/protein expression of iNOS and COX-2 in LPS-stimulated RAW264.7 cells. FM also reduced the secretion of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1 in LPS-stimulated RAW264.7 cells. Results also demonstrated that FM improved inflammatory response in LPS-stimulated A549 airway epithelial cells by inhibiting the production of cytokines, such as IL-1β, IL-6 and TNF-α. In addition, FM suppressed MAPK activation and NF-κB nuclear translocation induced by LPS. FM also upregulated the mRNA/protein expression levels of heme oxygenase-1 and the nuclear translocation of nuclear factor erythroid 2-related factor 2 in RAW264.7 cells. In an experimental animal model of LPS-induced acute lung injury, the increased levels of molecules in bronchoalveolar lavage (BAL) fluid were suppressed by FM administration. Collectively, it was founded that FM has anti-inflammatory properties on activated-macrophages by suppressing inflammatory molecules and regulating the activation of MAPK/NF-κB signaling.

• Tuberculosis and Respiratory Diseases
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• v.49 no.2
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• pp.207-216
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• 2000

Background : The occurrence of lung complications after allogenic bone marrow transplantation(BMT) has been reported as 40-60 percent. The risk factors for lung complications are whole body irradiation, high dose chemotherapy, graft versus host disease, old age and CMV infection. The prevalence of graft versus host disease is less in Korea than in Western countries, but frequency of CMV infection is higher. Therefore, the pattern of lung complications may be different in Korea from those in Western countries. Methods : A retrospective cohort study was performed on one hundred consecutive adult patients who underwent allogenic bone marrow transplantation from December, 1993 to May, 1999 at Asan Medical Center. Lung complications were divided into two groups by the time of development, within 30days (pre-engraftment) and beyond 30 days (post-engraftment), and then subdivided into infectious and non-infectious complication. Infectious complications were defined as having the organism in blood, BAL fluid, pleural fluid or sputum, or compatible clinical findings in patients, which improved with antibiotics or an anti-fungal therapy. Result: 1) Eighty three episodes of lung complications had occurred in 54 patients. 2) Within thirty days after BMT, non-infectious complications were more common than infections, but this pattern was reversed after 30 days. After one year post-BMT, there was no infectious complication except in cases of recurrence of underlying disease or development of chronic GVHD. 3) Among the non-infectious complications, pleural effusion (27 episodes) was most common, followed by pulmonary edema (8 episodes), bronchiolitis obliterans(2 episodes), diffuse alveolar hemorrhage (1 episode) and bronchiloitis obliterans with organizing pneumonia (1 episode). 4) The infectious complications were pneumonia (bacterial: 9 episodes, viral: 4 episodes, fungal : 5 episodes, pneumocystis carinii : 1 episode), pulmonary tuberculosis(3 episodes) and tuberculous pleurisy (3 episodes). 5) Lung complications were more frequent in CMV positive patients and in patients with delayed recovery of neutrophil count. 6) The mortality was higher in the patients with lung complications. Conclusion : Lung complications developed in 54% after allogenic BMT and were associated with higher mortality.

• Journal of agricultural medicine and community health
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• v.35 no.4
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• pp.339-349
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• 2010

Objective: We surveyed awareness levels of brucellosis, Q fever and enterohemorrhagic Escherichia coli (EHEC) among dairy farmers in Gyeonggi Province to suggest directions for public education and public relations. Methods: We designed questionnaires to evaluate awareness of 3 major zooneses. We conducted a questionnaire survey to assess knowledge of the general characteristics of them, information sources for the awareness of zooneses, and the mode of transmission. Subjects were 716 workers from 482 dairy farms in Gyeonggi province. Results: The awareness levels for brucellosis, Q fever, and EHEC were 90.2%, 2.5% and 56.6%, respectively. Awareness of brucellosis and EHEC were tended to increase with higher number of school years. Television was the most common route of information for these zoonoses. Most common responses for questions concerning the method of transmission for each zoonoses, 'Contact with parturient fluid or placenta of animal' was 63.2% for brucellosis, 'Ingestion of raw meat or residual product' was 66.7% and 64.2% for Q fever and EHEC, respectively. The most common reason why dairy farmers think that it is difficult to prevent zoonoses was the inconvenience of wearing protection. Conclusions: Education programs for zoonoses, especially Q fever, are needed for dairy farmers. In addition, publicity information activities about prevention of zoonoses are needed for high risk groups, such as the dairy farmers surveyed.

• Tuberculosis and Respiratory Diseases
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• v.48 no.2
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• pp.236-245
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• 2000

Background: Transbronchial lung biopsy(TBLB) has known to yield useful information for pulmonary infiltrates of uncertain etiology, However, its safety and usefulness have not been conclusive in the critically ill patients with respiratory failure. Moreover, TBLB has not been recommended for patients with mechanical ventilation. This study was conducted to investigate the diagnostic values and risks of Will performed on critically ill patients at bedside to obtain information on the pulmonary infiltrate of unknown etiology. Methods: Twenty patients(21 admissions with 23 cases) with diffuse pulmonary infiltrates who were treated in a medical intensive care unit of a tertiary referral hospital from January 1994 to May 1998, were enrolled for the study. Their medical records were retrospectively reviewed. TBLB was opted when a noninvasive diagnostic work-up failed to reveal the cause for the pulmonary infiltrate. The procedure was performed at patients' bedside without assistance of fluoroscopy. Bronchial washing or bronchoalveolar lavage was performed on the same pulmonary segment before performing TBLB. Results: Adequate specimens were obtained in 18 cases(78%). TBLB provided a specific diagnosis in two cases. The results of TBLB suggested the underlying etiology in 9 cases; bacterial pneumonitis(4), hypersensitivity pneumonitis(1), polymyositis(1), radiation fibrosis(1), idiopathic pulmonary fibrosis(1), and BOOP(1). Therapeutic decisions were altered in 11 cases(47.8%) based on the TBLB results. Pneumocystis carinii was found in the BAL fluid of another case. Ten patients with a therapeutic change and ten patients without a management change had mortality rates of 40% and 80%, respectively. The APACHE III scores were significantly higher in patients with complications($72.8{\pm}21.8$) compared with those without complications ($48.3{\pm}18.9$)(p<0.05). The complication rates were higher in those with mechanical ventilation(50%) than in those without Mechanical ventilation(33%), but the difference was not statistically significant(p=0.3). Conclusions: TBLB may be a useful diagnostic option for critically ill patients with unknown cause of pulmonary infiltrates. However, it should be cautious be used with care for patients with mechanical ventilation or for severely ill patients.

• Clinical and Experimental Pediatrics
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• v.49 no.8
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• pp.889-894
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• 2006

Purpose : Asthma is characterized by the presence of airway hyperresponsiveness(AHR) and inflammation. The extensive eosinophil infiltration into the lung is the hallmark of asthma and contributes to the damage of respiratory epithelium during late phase airway responses. Eotaxin is the major eosinophil chemoattractant found in bronchoalveolar lavage(BAL) fluid of allergic inflammation. IL-13 has been known to induce the expression of exotaxin and eosinophilia. IL-13 also induces airway inflammation, mucus production and leads to marked fibrosis, airway remodeling and AHR. We investigated whether serum IL-13 levels can reflect the presence of airway hyperresponsiveness in children with asthma, and the relationship between serum IL-13 and eotaxin levels. Methods : Using sandwich enzyme-linked immunosorbent assay, the serum IL-13 and eotaxin levels were measured in 13 atopic asthmatics, 5 atopic non-asthmatics and 12 control subjects. Metacholine challenge tests were performed in all subjects. Airway hyperresponsiveness to metacholine was expressed as provocative concentration of metacholine causing a 20% fall in FEV1[$PC_{20}mg/mL$]. $PC_{20}$ value of 25 mg/mL was used as a cut-off for defining a AHR. Results : Serum IL-13 levels showed positive correlation with eotaxin levels. Serum IL-13 and eotaxin levels showed no differences among atopic asthmatics, atopic non-asthmatics and control subjects. And there were no differences serum IL-13 and eotaxin levels in children with and without AHR and atopy. Serum IL-13 and eotaxin levels did not correlate with $logPC_{20}$ levels. Conclusion : IL-13 is closely related to the eotaxin release. But serum IL-13 and eotaxin per se can't predict the severity of airway hyperresponsiveness. IL-13 and eotaxin may have local effect on respiratory epithelium or there can be some factors to induce airway hyperresponsiveness other than serum IL-13 in asthmatic airways.