• Tuberculosis and Respiratory Diseases
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• v.70 no.6
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• pp.482-489
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• 2011

Background: Based on the assertion that apocynin diminishes acute lung injury (ALI) by inhibition of NADPH oxidase, the effect of apocynin was tested in interleukin-$1{\alpha}$ (IL-1)-induced ALI in rats. Methods: IL-1 was insufflated into the trachea of Sprague-Dawley rats to induce ALI, and apocynin (8 mg/kg) was given intravenously for inhibition of NADPH oxidase. In addition, we determined whether apocynin inhibited generation of superoxide anions from isolated human neutrophils. Five hours after IL-1 instillation, lung injury parameters, expression of cytosolic phospholipase A2 (cPLA2) by cells from bronchoalveolar lavage (BAL), an index of oxidative stress in lung tissues (${\gamma}$-glutamyltranspeptidase, activity), and ultrastructure of alveolar type II (AT II) cells were evaluated. Results: Apocynin decreased the generation of free radicals from phorbol myristate (PMA)-activated neutrophils in vitro, but did not ameliorate ALI. IL-1 induced enhancement of the expression of cPLA2 on neutrophils was not altered by apocynin. Conclusion: Apocynin induced suppression of the generation of superoxide anions from neutrophils by inhibition of NADPH oxidase does not attenuate IL-1-induced ALI in rats.

• Biomedical Science Letters
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• v.16 no.2
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• pp.83-90
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• 2010

Hesperidin, a member of the flavanone group of flavonoids, can be isolated in large amounts from the rinds of some citrus species [e.g., Citrus aurantium L. (bitter orange), Citrus sinensis L. (sweet orange) and Citrus unshiu Marcov. (satsuma mandarin)], and has been reported to have anticarcinogenic, antihypotensive and antimicrobial properties. Despite the efficacy of these polyphenolic compounds as immune modulators, the effects of the flavonoids are poorly understood about allergic effect. In this study, we investigated whether hesperidin could influence on Th1 and Th2 balance. Allergic reactions included an increase in the number of eosinophils in bronchoalveolar lavage (BAL) fluid, an increase in inflammatory cell infiltration into the lung tissue around blood vessels and airways, airway luminal narrowing, the development of airway hyper-responsiveness (AHR). The administration of hesperidin before the last airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. Accordingly, this study may provide evidence that hesperidin plays a critical role in the amelioration of the pathogenetic process of asthma in mice. These findings provide new insight into the immunopharmacological role of hesperidin in terms of its effects in a murine model of asthma, and also broaden current perspectives in our understanding of the immunopharmacological functions of hesperidin.

• Journal of Veterinary Clinics
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• v.26 no.4
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• pp.336-339
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• 2009

A 4-year-old, neutered male Shih-tzu dog weighing 5.4 kg was referred due to anorexia and chronic coughing. Based on history, physical examination, laboratory tests, radiographic findings, echocardiography, and bronchoscopic examination, the dog was diagnosed as tracheobronchial foreign body. The foreign body was steamed rice debris, which was removed by bronchoalveolar lavage (BAL) with vacuum suction of bronchoscopy. Bacterial and fungal culture of collected BAL fluid was negative. Baermann test for lungs parasites also was negative. The dog was treated with bronchodilator, antibiotics, anti-inflammatory agent, and mucolytics for 7 days. Appetite increased and coughing sign was clearly improved after removal of foreign body and medical therapy. This case report describes that bronchoscopic techniques are available for the evaluation and management of airway foreign bodies.

• Tuberculosis and Respiratory Diseases
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• v.70 no.5
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• pp.390-396
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• 2011

Background: Hyaluronan (HA) is an unbranched glycosaminoglycan. It has been proposed that HA acts as a vehicle for cytokines due to the strong negative charge on its surface. We hypothesized that HA would function like a cytokine scavenger and reduce the inflammatory signaling cascade and this would lead to improved survival in rats suffering with endotoxemia. Methods: Endotoxin (Salmonella, 10 mg/kg) or an equal amount of 0.9% NaCl (NS) was injected into the jugular vein of rats. HA (1,600 kDa, 0.35%) or NS was given at 0.1 mL/kg/h for 3 hours. HA or NS infusion was started at 4 hour after endotoxin injection. The rats were divided into the control and HA groups (n=16 for each group). The mean arterial pressure (MAP) was monitored during HA or normal saline infusion. Survival was assessed every 12 hours for 3 days throughout the experiment. Results: The survival rate (%) of the rats treated with HA was higher (60%) than that of the controls (20%) when HA was infused 4 hours after lipopolysaccharide (LPS) injection. The bronchoalveolar lavage (BAL) fluid of the animals surviving HA or NS infusion 4 hours after LPS showed that the total cell counts and number of neutrophils were significantly (p < 0.01) reduced in the HA treated groups compared with that of the controls (total cell count, $9.2{\times}10^4$/mL vs. $61{\times}10^4$/mL; neutrophils, $21{\times}10^4$/mL vs. $0.2{\times}10^4$/mL, respectively). There was no significant MAP difference between the HA or control groups either with or without endotoxin. Conclusion: Infusion of hyaluronan (1,600 kDa) reduced the BAL total cell count and the number of neutrophils and it improved the survival rate of the endotoxemic rats.

• Toxicological Research
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• v.31 no.2
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• pp.181-189
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• 2015

In recent years, the use of both nano- and micro-sized lanthanum has been increasing in the production of optical glasses, batteries, alloys, etc. However, a hazard assessment has not been performed to determine the degree of toxicity of lanthanum. Therefore, the purpose of this study was to identify the toxicity of both nano- and micro-sized lanthanum oxide in cultured cells and rats. After identifying the size and the morphology of lanthanum oxides, the toxicity of two different sized lanthanum oxides was compared in cultured RAW264.7 cells and A549 cells. The toxicity of the lanthanum oxides was also analyzed using rats. The half maximal inhibitory concentrations of micro-$La_2O_3$ in the RAW264.7 cells, with and without sonication, were 17.3 and 12.7 times higher than those of nano-$La_2O_3$, respectively. Similar to the RAW264.7 cells, the toxicity of nano-$La_2O_3$ was stronger than that of micro-$La_2O_3$ in the A549 cells. We found that nano-$La_2O_3$ was absorbed in the lungs more and was eliminated more slowly than micro-$La_2O_3$. At a dosage that did not affect the body weight, numbers of leukocytes, and concentrations of lactate dehydrogenase and albumin in the bronchoalveolar lavage (BAL) fluids, the weight of the lungs increased. Inflammatory effects on BAL decreased over time, but lung weight increased and the proteinosis of the lung became severe over time. The effects of particle size on the toxicity of lanthanum oxides in rats were less than in the cultured cells. In conclusion, smaller lanthanum oxides were more toxic in the cultured cells, and sonication decreased their size and increased their toxicity. The smaller-sized lanthanum was absorbed more into the lungs and caused more toxicity in the lungs. The histopathological symptoms caused by lanthanum oxide in the lungs did not go away and continued to worsen until 13 weeks after the initial exposure.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.6
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• pp.1593-1597
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• 2006

We hope to evaluate the effects of Gami-Choakwiyeum (GCKY) on the PPAR-${\gamma}$’ in the OVA induced asthma mouse model. Female BALB/c mice, 8 weeks of age and free of murine specific pathogens were used. Mice were sensitized by intraperitoneal injection of OVA emulsified in aluminum hydroxide in a total volume of 200 ${\mu}{\ell}$ on one day and 14 days. On 21, 22, and 23 days after the initial intraperitoneal injection of OVA, the mice were challenged using an ultrasonic nebulizer. GCKY was administered 7 times by oral gavage at 24 hour intervals fromdays 19 after intraperitoneal injection of OVA. Bronchoalveolar lavage was perfromed 72 hours after the last challenge, and total cell numbers in the BAL fluid were counted. Also, the level of PPAR-${\gamma}$ of normal and OVA-induced asthma moused with/without administration of GCKY were measured by Western blot analysis. For the histologic examination, the specimens were stained with hematoxylin 2 and eosin-Y.(H & E). Numbers of total cells were increased significantly at 72 h after OVA inhalation compared with numbers of total cells in the normal and the administration of GCKY. Especially, the increased numbers of eosinophils in BAL fluids after OVA inhalation were significantly increased. However, the numbers of eosinophils reduced by the administration of GCKY. Western blot analysis revealed that PPAR-${\gamma}$ levels in nuclear level were increased slightly after OVA inhalation compared with the levels in the normal group. After the administration of GCKY, PPAR-${\gamma}$ levels in cytosolic and nuclear levels at 72 h after OVA inhalation were markedly increased. On pathologic examination, there were many acute inflammatory cells around the alveoli, bronchioles, and airway lumen of mice with OVA-induced asthma compared with inflammatory cells in the normal group. However, acute inflammatory cells around alveoli, bronchioles, and airway lumen markedly decreased after administration of GCKY, GCKY can increase a PPAR-${\gamma}$ level and could be an effective treatment in asthma patients through the PPAR-${\gamma}$ mechanism for bronchial asthma.

• IMMUNE NETWORK
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• v.20 no.3
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• pp.25.1-25.13
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• 2020

Acinetobacter baumannii is known for its multidrug antibiotic resistance. New approaches to treating drug-resistant bacterial infections are urgently required. Cathelicidin-related antimicrobial peptide (CRAMP) is a murine antimicrobial peptide that exerts diverse immune functions, including both direct bacterial cell killing and immunomodulatory effects. In this study, we sought to identify the role of CRAMP in the host immune response to multidrug-resistant Acinetobacter baumannii. Wild-type (WT) and CRAMP knockout mice were infected intranasally with the bacteria. CRAMP^-/- mice exhibited increased bacterial colony-forming units (CFUs) in bronchoalveolar lavage (BAL) fluid after A. baumannii infection compared to WT mice. The loss of CRAMP expression resulted in a significant decrease in the recruitment of immune cells, primarily neutrophils. The levels of IL-6 and CXCL1 were lower, whereas the levels of IL-10 were significantly higher in the BAL fluid of CRAMP^-/- mice compared to WT mice 1 day after infection. In an in vitro assay using thioglycollate-induced peritoneal neutrophils, the ability of bacterial phagocytosis and killing was impaired in CRAMP^-/- neutrophils compared to the WT cells. CRAMP was also essential for the production of cytokines and chemokines in response to A. baumannii in neutrophils. In addition, the A. baumannii-induced inhibitor of κB-α degradation and phosphorylation of p38 MAPK were impaired in CRAMP^-/- neutrophils, whereas ERK and JNK phosphorylation was upregulated. Our results indicate that CRAMP plays an important role in the host defense against pulmonary infection with A. baumannii by promoting the antibacterial activity of neutrophils and regulating the innate immune responses.

• Clinical and Experimental Pediatrics
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• v.53 no.4
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• pp.481-487
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• 2010

Purpose: Recently many studies show early exposure during childhood growth to endotoxin (lipopolysaccharides, LPS) and/or early exposure to allergens exhibit important role in development of allergy including bronchial asthma. The aim of this study was to evaluate the role of endotoxin and allergen exposure in early life via the airways in the pathogenesis of allergic airways inflammation and airway hyperresposiveness (AHR) in mouse model of asthma. Methods: Less than one week-old Balb/c mice was used. Groups of mice were received either a single intranasal instillation of sterile physiologic saline, 1% ovalbumin (OVA), LPS or $1.0{\mu}g$ LPS in 1% OVA. On 35th day, these animals were sensitized with 1% OVA for 10 consecutive days via the airways. Animals were challenged with ovalbumin for 3 days on 55th days, and airway inflammation, hyperresponsiveness, and cytokine expression were assessed. Measurements of airway function were obtained in unrestrained animals, using whole-body plethysmography. Airway responsiveness was expressed in terms of % enhanced pause (Penh) increase from baseline to aerosolized methacholine. Lung eosinophilia, serum OVA-IgE and bronchoalveolar lavage (BAL) fluid cytokine levels were also assessed. ANOVA was used to determine the levels of difference between all groups. Comparisons for all pairs were performed by Tukey-Kramer honest significant difference test; $P$ values for significance were set to 0.05. Results: Sensitized and challenged mice with OVA showed significant airway eosinophilia and heightened responsiveness to methacholine. Early life exposure of OVA and/or LPS via the airway prevented both development of AHR as well as bronchoalveolar lavage fluid eosinophilia. Exposure with OVA or LPS also resulted in suppression of interleukin (IL)-4, 5 production in BAL fluid and OVA specific IgE in blood. Conclusion: These results indicate that antigen and/or LPS exposure in the early life results in inhibition of allergic responses to OVA in this mouse model of astham. Our data show that early life exposure with OVA and/or LPS may have a protective role in the development of allergic airway inflammation and development of allergen-induced airway responses in mouse model of asthma.

• Tuberculosis and Respiratory Diseases
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• v.42 no.4
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• pp.569-583
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• 1995

Background: The expression of the adhesion molecules on the cell surface is important in the movement of cells and the modulation of immune response. DILD starts as an alveolitis and progresses to pulmonary fibrosis. So adhesion molecules in these patients is expected to be increased. There are several reports about adhesion molecules in DILD in terms of the percentage of positive cells in immuno-stain, in which the interpretation is subjective and the data were variable. Methods: So we measured the relative median fluorescence intensity(RMFI) which is the ratio of the FI emitted by bound primary monoclonal antibody to FI emitted by isotypic control antibody of the cells in BALF of 28 patients with DILD(IPF:10, collagen disease:7, sarcoidosis:9, hypersensitivity pneumonitis:2) and 9 healthy control. Results: RMFI of the ICAM-1 on AM($3.30{\pm}1.16$) and lymphocyte($5.39{\pm}.70$) of DILD were increased significantly than normal control($0.93{\pm}0.18$, $1.06{\pm}0.21$, respectively, p=0.001, P=0.003). RMFI of the CD18 on lymphocyte was also higher($24.9{\pm}14.9$) than normal($4.59{\pm}3.77$, p=0.0023). And there was a correlation between RMFI of ICAM on AM and the % of AM(r=-0.66, p=0.0001) and lymphocyte(r=0.447, p=0.0116) in BALF. Also RMFI of ICAM on lymphocyte had a significant (r=0.593, p=0.075) correlation with the % of IL-2R(+) lymphocyte in BALF. The soluble ICAM(sICAM) in serum was also significantly elevated in DILD($499.7{\pm}222.2\;ng/ml$) compred to normal($199.0{\pm}38.9$) (p=0.00097) and sICAM in BAL fluid was also significantly higher than normal control group($41.8{\pm}23.0\;ng/ml$ vs $20.1{\pm}13.6\;ng/ml$). There was a Significant correlation between sICAM level in serum and the expression of ICAM-l on AM(r=0.554, p=0.0259).Conclusion: These data suggest that in DILD the expression of adhesion molecules is increased in the AM and BAL lymphocytes with elevated serum sICAM, and these parameter may be useful in determining disease activity.

• Tuberculosis and Respiratory Diseases
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• v.44 no.2
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• pp.349-359
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• 1997

Background : The signal pathways and their precise roles for acute respiratory distress syndrome caused by endotoxin (ETX) has not been established. Since there has been several in vitro experiments suggesting that activation of protein kinase C (PKC) pathway may be responsible for endotoxin-induced inflammatory reaction, we performed in vivo experiments in the rats with the hypothesis that PKC-inhibition can effectively prevent endotoxin-induced acute lung injury. Methods : We studied the role of PKC in ETX-induced ALI using PKC inhibitor (staurosporine, STP) in the rat Specific pathogen free male Sprague-Dawley weighted from 165 to 270g were used for the study. Animals were divided into the normal control (NC)-, vehicle control (VC)-, ETX-, PMA (phorbolmyristateacetate)-, STP+PMA-, and STP+ETX-group. PMA (50mg/kg) or ETX (7mg/kg) was instilled through polyethylen catheter after aseptic tracheostomy with and without STP (0.2mg/kg)-pretreatment STP was injected via tail vein 30min before intratracheal injection (IT) of PMA or ETX. Bronchoalveolar lavage (BAL) was done 3-or 6-hrs after IT of PMA or ETX respectively, to measure protein concentration, total and differential cell counts. Results : The results were as follows. The protein concentrations in BALF in the PMA- and ETX-group were very higher than that of VC-group (p<0.001). When animals were pretreated with STP, the %reduction of the protein concentration in BALF was $64.8{\pm}8.5$ and $30.4{\pm}2.5%$ in the STP+PMA- and STP+ETX-group, respectively (p = 0.028). There was no difference in the total cell counts between the PMA-and VC-group (p = 0.26). However the ETX-group showed markedly increased total cell counts as compared to the VC- (p = 0.003) and PMA-group (p = 0.0027), respectively. The total cell counts in BALF were not changed after pretreatment with STP compared to the PMA- (p = 0.22) and ETX-group (p = 0.46). The percentage of PMN, but not alveolar macrophage, was significantly elevated in the PMA-, and ETX-group. Especially in the ETX-group, the percentage of PMN was 17 times higher than that of PMA (p < 0.001). The differential cell counts was not different between the PMA and STP+PMA On the contrary the STP+ETX-group showed decreased percentage of PMN (p = 0.016). There was no significant relationship between the protein concentration and the total or differential cell counts in each group. Conclusion : Pretreatment with PKC-inhibitor (staurosporine) partially but significantly inhibited ETX-induced ALI.