• Tuberculosis and Respiratory Diseases
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• v.56 no.1
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• pp.51-66
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• 2004

Objectives : The matrix metalloproteinases (MMPs) that participate in the extracellular matrix metabolism play a important role in the progression of pulmonary fibrosis. The effects of the MMPs are regulated by several factors including Th-1 cytokines, $interferon-{\gamma}$ ($IFN-{\gamma}$). Up to now, $IFN-{\gamma}$ is known to inhibit pulmonary fibrosis, but little is known regarding the exact effect of $IFN-{\gamma}$ on the regulation of the MMPs. This study investigated the effects of $interferon-{\gamma}$ on the pulmonary fibrosis and the expression of the lung MMP-2,-9, TIMP-1,-2, and Th-2 cytokines in aa rat model of bleomycin induced pulmonary fibrosis. Materials and methods : Male, specific pathogen-free Sprague-Dawley rats were subjected to an intratracheal bleomycin instillation. The rats were randomized to a saline control, a bleomycin treated, and a bleomycin+$IFN-{\gamma}$ treated group. The bleomycin+$IFN-{\gamma}$ treated group was subjected to an intramuscular injection of $IFN-{\gamma}$ for 14 days. At 3, 7, 14, and 28 days after the bleomycin instillation, the rats were sacrificed and the lungs were harvested. In order to evaluate the effects of the $IFN-{\gamma}$ on lung fibrosis and inflammation, the lung hydroxyproline content, inflammation and fibrosis score were measured. Western blotting, zymography and reverse zymography were performed at 3, 7, 14, 28 days after bleomycin instillation in order to evaluate the MMP-2,-9, and TIMP-1,-2 expression level. ELISA was performed to determine the IL-4 and IL-13 level in a lung homogenate. Results : 1. 7 days after bleomycin instillation, inflammatory changes were more severe in the bleomycin+$IFN-{\gamma}$ group than the bleomycin group (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$2.08{\pm}0.15:2.74{\pm}0.29$, P<0.05), but 28 days after bleomycin instillation, lung fibrosis was significantly reduced as a result of the $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$3.94{\pm}0.43:2.64{\pm}0.13$, P<0.05). 2. 28 days after bleomycin instillation, the lung hydroxyproline content was significantly reduced as a result of $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$294.04{\pm}31.73{\mu}g/g:194.92{\pm}15.51{\mu}g/g$, P<0.05). 3. Western blotting showed that the MMP-2 level was increased as a result of the bleomycin instillation and highest in the 14 days after bleomycin instillation. 4. In zymography, the active forms of MMP-2 were significantly increased as a result of the $IFN-{\gamma}$ treatment 3 days after the bleomycin instillation, bleomycin+$IFN-{\gamma}$ group (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$209.63{\pm}7.60%:407.66{\pm}85.34%$, P<0.05), but 14 days after the bleomycin instillation, the active forms of MMP-2 were significantly reduced as a result of the $IFN-{\gamma}$ treatment (bleomycin group : bleomycin+$IFN-{\gamma}$ group=$159.36{\pm}20.93%:97.23{\pm}12.50%$, P<0.05). 5. The IL-4 levels were lower in the bleomycin and bleomycin+$IFN-{\gamma}$ groups but this was not significant, and the IL-13 levels showed no difference between the experiment groups. Conclusion : The author found that lung inflammation was increased in the early period but the pulmonary fibrosis was inhibited in the late stage as a result of $IFN-{\gamma}$. The inhibition of pulmonary fibrosis by $IFN-{\gamma}$ appeared to be associated with the inhibition of MMP-2 activation by $IFN-{\gamma}$. Further studies on the mechanism of the regulation of MMP-2 activation and the effects of MMP-2 activation on pulmonary fibrosis is warranted in the future.

• Journal of Korean Society for Atmospheric Environment
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• v.18 no.E2
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• pp.121-128
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• 2002

This study was carried out to investigate if nitric oxide synthase (NOS) inhibitors modulate airway inflammation induced by diesel exhaust particles (DEP). N$\^$G/-nitro-L-arginine methyl ester (L-NAME), a potent constitutive NOS (cNOS) inhibitor, and aminoguanidine (AG), a selective inducible NOS (iNOS) inhibitor, were administered to mice in their drinking water for 7 weeks. Airway inflammation was elicited by the repeated intratracheal administration of DEP. The results showed that macrophages, inflammatory eosinophils and neutrophils in bronchoalveolar lavage (BAL) fluids by intratracheal DEP instillation were significantly suppressed in the mice treated with two NOS inhibitors toghther with DEP. The suppression of these cells was more effective in AG treated groups than in L -NAME treated groups. NOS inhibitor treatment also reduced interleukin -5 (IL-5 in the BAL fluids and lung homogenates. Additionally, it was found that eosinophil peroxidase (EPO) activity in the BAL fluids was also decreased by NOS inhibitor treatment. These results suggest that nitric oxide (NO) is produced in airway inflammation by repeated DEP instillation, and that iNOS inhibition as well as cNOS inhibition can play a modulating role in this airway inflammation by DEP.

• Clinical and Experimental Pediatrics
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• v.60 no.9
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• pp.273-281
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• 2017

To date, preterm infants with respiratory distress syndrome (RDS) after birth have been managed with a combination of endotracheal intubation, surfactant instillation, and mechanical ventilation. It is now recognized that noninvasive ventilation (NIV) such as nasal continuous positive airway pressure (CPAP) in preterm infants is a reasonable alternative to elective intubation after birth. Recently, a meta-analysis of large controlled trials comparing conventional methods and nasal CPAP suggested that CPAP decreased the risk of the combined outcome of bronchopulmonary dysplasia or death. Since then, the use of NIV as primary therapy for preterm infants has increased, but when and how to give exogenous surfactant remains unclear. Overcoming this problem, minimally invasive surfactant therapy (MIST) allows spontaneously breathing neonates to remain on CPAP in the first week after birth. MIST has included administration of exogenous surfactant by intrapharyngeal instillation, nebulization, a laryngeal mask, and a thin catheter. In recent clinical trials, surfactant delivery via a thin catheter was found to reduce the need for subsequent endotracheal intubation and mechanical ventilation, and improves short-term respiratory outcomes. There is also growing evidence for MIST as an alternative to the INSURE (intubation-surfactant-extubation) procedure in spontaneously breathing preterm infants with RDS. In conclusion, MIST is gentle, safe, feasible, and effective in preterm infants, and is widely used for surfactant administration with noninvasive respiratory support by neonatologists. However, further studies are needed to resolve uncertainties in the MIST method, including infant selection, optimal surfactant dosage and administration method, and need for sedation.

• The Journal of the Korean bone and joint tumor society
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• v.2 no.1
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• pp.65-71
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• 1996

Twenty-nine cases of unicameral bone cyst developed in long bone of children have been treated and followed up for 4.5 years in average form Department of Orthopaedic Surgery, Guro Hospital, Korea University, College of Medicine since September, 1983, Treatment for those lesions differed to form largely two groups, one of which consised of insillation of Methyl-prednisolone for non-weight bearing bones(12 humeri) and the other of curettage and autogenous bone graft for weight-bearing bones(7 femur). Methl-prednisolone group required repetition of instillation for 3.5 time in average spanning over 4 years until cloudy obliteration occurs. Curettage and bone graft had healed in 3 year 6 months' time in average. There were neither recurrence nor pathologic fractures of the lesions with the latter group. Immobilization period was virtually non with Methyl-prednisolone group and 4-6 weeks by hip spica with curettage and bone graft group. As conclusions, It seems confirmed that treatment strategy of unicameral bone cyst consisted of Methyl-prednisolone instillation for humerus lesions and early curettage and bone graft for femur lesions is applicable as guideline having solid ground in clinical experiences.

• Korean Journal of Poultry Science
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• v.19 no.1
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• pp.17-25
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• 1992

The efficacy of B$_1$l live vaccine which is used successfully in chicken was examined against Newcastle disease in quails. A total of 480 male quails were divided into 4 groups, of which 3 groups were vaccinated via drinking water, eye instillation and spraying method and the remaining was employed as a nonvaccinated control group. At 3 weeks after the first vaccination a part of quails in each group was revaccinated. Efficacy of the vaccine was evaluated by the antibody responses and the protection rates after challenge with a virulent NDV. Vaccination of quails with $B_1$ NDV at 10 days of age resulted in beneficial effect compared to nonvaccinated group regardness of vaccination methods adopted although general protection rates were considerably low. Twice vaccination gave higher protection than once vaccination. Hemagglutination inhibition antibody responeses were significantly higher in groups of quails vaccinated by spray and eye instillation method than by drinking water administration. Antibody responses were marked at 2 weeks onward and until 5 to 7 weeks after vaccination. Antibody responses were rapid and marked after second vaccination. However, antibody level did not last longer than 5 to 7 weeks postvaccination. Vaccine caused no adverse effect on quails in terms of growth'rate, body temperature or clinical signs.

• Journal of Korean Society for Atmospheric Environment
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• v.24 no.3
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• pp.321-328
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• 2008

The number of patient with allergic asthma and atopy have increased in the cities of Korea steadily. In order to elucidate the primary factor, we investigated whether the house dust particles collected from an apartment of the middle classes has promoting effects of allergen-related airway inflammation and airway hyperresponsiveness. Mice were treated with 0.1 mL of 1 mg/mL of house dust particles suspension by intratracheal instillation once weekly for 10 weeks combined with ovalalbumin (OVA) sensitization. Intratracheal instillation of house dust particles and OVA sensitization caused an increase in the level of serum L-lactate dehydrogenase (LDH), immunoglobulun-E (IgE) and histamine, and an elevation in respiratory resistance. It also enhanced infiltration of eosinophils in the bronchoalveolar lavage fluid (BALF) of mice, IgE and eotaxin expression in blood, and T helper type 2 cell derived cytokine levels such as of interleukin (IL)-4, IL-13 and IL-5 in the BALF. However, it did not influence T helper type 1 cytokine such as interferon-gamma in the BALF. These results indicate that house dust particles elevate allergen-related airway inflammation and airway hyperresponsiveness in mice and may play an important role in the aggravation of asthma and atopy in Korea.

• Environmental Analysis Health and Toxicology
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• v.25 no.2
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• pp.121-129
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• 2010

This study was carried out to investigate whether asian yellow sand dust (AS) has promoting effects of allergen-related airway inflammation and airway hyperresponsiveness, because the number of patient with allergic asthma and atopy, and with chronic bronchial inflammation and pneumonia have increased steadily in the cities of Korea. The appearance of AS collected was all round and flat, and the diameter was mostly below about 5 ${\mu}m$. When mice were treated with AS suspension by intratracheal instillation combined with ovalalbumin(OVA) sensitization chronically, the level of serum L-lactate dehydrogenase (LDH), IgE and histamine, and respiratory resistance was increased. Intratracheal instillation of AS and OVA also enhanced infiltration of eosinophils in the bronchoalveolar lavage fluid (BALF), IgE and eotaxin expression, and T helper type 2 cell derived cytokines of interleukin (IL)-4, IL-13 and IL-5 as major contributors to allergy and asthma. These results indicate that AS elevates allergen-related airway inflammation and airway hyperresponsiveness in mice and may play an important role in the aggravation of respiratory diseases in Korea.

• The Journal of Pediatrics of Korean Medicine
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• v.23 no.3
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• pp.217-231
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• 2009

Objectives To evaluate that Okwada affected which factors for treatment of lung fibrosis. Methods Bleomycin induced lung fibrosis model made in mice. After Okwada lyophilized, power sample obtained and melt in distilled water. Okwada solution administered mice through oral route on 21 days after bleomycin instillation and this procedure performed once a day for 7 days. We divided by three groups; normal (control), bleomycin induced lung fibrosis without treatment (experimental), bleomycin induced lung fibrosis with treatment (treatment). On six weeks after bleomycin instillation, mice sacrificed and removed lung. We performed Western blot analysis for TGF-beta, phosphodiesterase 5A, interleukin (4,5,13) and compared therapeutic effects of Okwada. Results On western blot analysis, all normal and experimental mice detected TGF-beta, phosphodiesterase 5A, interleukin 4,5,13. The amount of band of TGF-beta, phosphodiesterase 5A, interleukin 5 in experimental and treatment group was similar. However, interleukin 4,13 of treatment group decreased compared with experimental group. Conclusions Okwada would be effected the lung fibrosis through suppression of interleukin 4,13.

• Journal of Chest Surgery
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• v.7 no.1
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• pp.1-8
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• 1974

Acute pulmonary edema was induced by intravenous injection of epinephrine, intravenous infusion of dextran and intratracheal instillation of acid solution index was determined from pressure volume curves in excised lungs. Surface activity was also investigated with measurements of maximum and minimum surface tension and stability index on saline extracts of same lungs. The results were as follows. 1. The expansion index of excised lung in which pulmonary edema was induced by intravenous injection of epinephrine, intravenous infusion of dextran and intratracheal instillation of acid solution was ignificantly decreased as compared with the normal control of $0.86{\pm}0.017$ to $0.74{\pm}0.03$, $0.71{\pm}0.081$and $0.76{\pm}0.02$, respectively. 2. The deflation curves of excised lungs in which pulmonary edema was induced were significantly decreased as compared with the normal controls. 3. The minimum surface tension of excised lung in which pulmonary edema was induced was significantly increased in each groups and stability index was significantly decreased as compared with the normal controls 0.78 to $0.35{\pm}0.039$, $0.29{\pm}0.02 $ and $0.31{\pm}0.083$, respectively. 4. The decrease of pulmonary surface activity in acute pulmonary edema was in proportion to the degree of pulmonary edema regardless of their etiology.

• Neonatal Medicine
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• v.16 no.2
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• pp.101-109
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• 2009

Pulmonary surfactant (PS) therapy in premature infants has a remarkable impact on improving survival and outcomes in neonatal respiratory distress syndrome (RDS). Early PS therapy involves instillation of PS upon delivery of very premature infants or if there is evidence of RDS, such as an increased requirement of oxygen 2 hours after birth, especially in infants <30 weeks gestation. Early PS treatment in very premature infants results in a significant reduction in the severity of RDS, mortality, and incidence of pneumothorax, pulmonary interstitial emphysema, and bronchopulmonary dysplasia in comparison with late PS treatment. According to European and American consensus guidelines on the management of neonatal RDS, early PS instillation should be considered for infants <30 weeks gestation, infants with a birth weight <1,250 g, or if the mother has not received antepartum corticosteroids. We suggest that the Korean health insurance policy on RDS be modified so that PS can be used for better clinical outcomes of very premature infants.