The role of FGF-2 in smoke-induced emphysema and the therapeutic potential of recombinant FGF-2 in patients with COPD

Kim, You-Sun,Hong, Goohyeon,Kim, Doh Hyung,Kim, Young Min,Kim, Yoon-Keun,Oh, Yeon-Mok,Jee, Young-Koo Nature Publishing Group UK 2018 Experimental and molecular medicine Vol.50 No.11

<▼1><P>Although the positive effects of recombinant fibroblast growth factor-2 (rFGF-2) in chronic obstructive pulmonary disease (COPD) have been implicated in previous studies, knowledge of its role in COPD remains limited. The mechanism of FGF2 in a COPD mouse model and the therapeutic potential of rFGF-2 were investigated in COPD. The mechanism and protective effects of rFGF-2 were evaluated in cigarette smoke-exposed or elastase-induced COPD animal models. Inflammation was assessed in alveolar cells and lung tissues from mice. FGF-2 was decreased in the lungs of cigarette smoke-exposed mice. Intranasal use of rFGF-2 significantly reduced macrophage-dominant inflammation and alveolar destruction in the lungs. In the elastase-induced emphysema model, rFGF-2 improved regeneration of the lungs. In humans, plasma FGF-2 was decreased significantly in COPD compared with normal subjects (10 subjects, <I>P</I> <I>=</I> 0.037). The safety and efficacy of inhaled rFGF-2 use was examined in COPD patients, along with changes in respiratory symptoms and pulmonary function. A 2-week treatment with inhaled rFGF-2 in COPD (<I>n</I> = 6) resulted in significantly improved respiratory symptoms compared with baseline levels (<I>P</I> <I><</I> 0.05); however, the results were not significant compared with the placebo. The pulmonary function test results of COPD improved numerically compared with those in the placebo, but the difference was not statistically significant. No serious adverse events occurred during treatment with inhaled rFGF-2. The loss of FGF-2 production is an important mechanism in the development of COPD. Inhaling rFGF-2 may be a new therapeutic option for patients with COPD because rFGF-2 decreases inflammation in lungs exposed to cigarette smoke.</P></▼1><▼2><P><B>Lung disease: Inhaling a protein might help</B></P><P>Studies on the role of the protein ‘fibroblast growth factor-2’ (FGF-2) in chronic obstructive pulmonary disease (COPD) suggest that inhaled FGF-2 could help treat the emphysema linked to smoking. Researchers in South Korea led by Young-Koo Jee at Dankook University, Cheonan, and Yeon-Mok Oh at the University of Ulsan, Seoul, studied the role of the reduced FGF-2 levels found in mice with lung inflammation caused by exposure to cigarette smoke. They also uncovered details of a protective effect of inhaled FGF-2, identifying specific cellular and lung structure changes attributed to the administered FGF-2. Reduced FGF-2 levels were also found in patients with COPD. Initial trials revealed some improvement in patients treated with FGF-2, but not at a statistically significant level. Nevertheless, the authors suggest their results justify further investigation of the protein’s therapeutic potential.</P></▼2>

이산화질소, 암모니아 및 수분의 기상반응에 의한 암모늄염 생성 거동에 관한 연구

목영선,이호원,현영진 제주대학교 해양과환경연구소 2001 해양과환경연구소 연구논문집 Vol.25 No.-

This study investigates the kinetics of the gas phase reaction between nitrogen dioxide, ammonia and water vapor, and presents the appropriate ranges of the process variables such as initial NO_2 concentration, absolute humidity and reaction temperature for the effective removal of nitrogen dioxide. According to the kinetic calculations, the gas phase reaction for the removal of NO_2 takes effectively place at the water vapor content higher than 4-6 %(v/v), but further increase in the water vapor content does not significantly enhance the removal. The residence time required to achieve a desired removal efficiency of NO_2 was found to increase with the decrease in its initial concentration. Especially, the residence time required rapidly increases when the initial concentration of NO_2 is less than 100 ppm. The removal rate of NO_2 is in inverse proportion to the reaction temperature, i.e., lower temperature is favorable to promote the removal rate. The results obtained in this study may be useful for the determination of the optimal values of the process variables in non-thermal plasma technology for the removal of nitrogen oxides.

저온 플라즈마를 이용한 휘발성 유기화합물의 분해에 관한 연구

목영선,이호원,현영진 제주대학교 환경연구소 2000 환경연구논문집 : 제주대 Vol.8 No.-

A non-thermal plasma process using pulsed corona discharge was applied to the destruction of a volatile organic compound (propene). Propene was found to be easily destroyed by this process, and the destruction efficiency was proportional to the supplied power while it was in inverse proportion to the initial propene concentration. Ethane and formaldehyde were detected at the reactor outlet, but the concentrations of such byproducts were negligible. The destruction rate equation (first order in terms of propene concentration) and the rate constant (6.75×10^(3)s^(1)W^(1)) proposed were validated by the comparison between the calculations and experimental data. The increases in the contents of oxygen and water vapor decreased the pulse energy delivered to the plasma reactor. At the initial concentration of 5.85 X 10^(3) mol/㎥, the average energy requirement to destroy one molecule of propene was in the range of 26 to 47 eV according to the amount of propene destroyed, which is relatively low value, compared with that of nitric oxide(NO).

기체 전기방전을 이용한 리액티브 블루 4의 분해에 관한 연구

목영선,조진오,이호원 제주대학교 공과대학 첨단기술연구소 2006 尖端技術硏究所論文集 Vol.17 No.1

Gaseous electrical discharge is an effective method available for the production of ozone and ultraviolet light. The wastewater treatment system of this study was designed to utilize both ozone and ultraviolet light produced by the electrical discharge for the degradation- of organic contaminants. The electrical discharge device (DBD reactor) consisted of a quartz cylinder, a coaxial ceramic tube inside of which a steel rod was placed (discharging electrode), and a steel wire that was helically wound around the quartz cylinder (ground electrode). The DBD reactor was immersed in the wastewater in order that the ultraviolet light could irradiate the wastewater. The ozone-containing gas from the DBD reactor was sparged throughout the wastewater. An anthraquinone-based dye, Reactive Blue 4, was chosen as the organic contaminant. The experimental results showed that the present system was very effective for the degradation of the organic contaminant. The energy requirement for the degradation was found to be 0.42kJ/mg, on the basis of 90% chromaticity removal.

이산화질소, 암모니아 및 수분의 기상반응에 의한 암모늄염 생성 거동에 관한 연구

목영선,이호원,현영진 제주대학교 해양연구소 2001 해양자원연구소연구보고 Vol.25 No.-

교류 유전체 방전 공정에 의한 휘발성유기화합물 분해 및 전력공급에 관한 연구

목영선,이호원,현영진 제주대학교 해양연구소 2001 해양자원연구소연구보고 Vol.25 No.-

실내공기정화기에서 먼지 및 유기물화합물의 동시 제거에 관한 연구

목영선,강호철,이호원,현영진 제주대학교 공과대학 첨단기술연구소 2002 尖端技術硏究所論文集 Vol.13 No.1

The indoor air cleaner used in this study consisted of a plasma reactor followed by an electrostatic precipitator. The role of the electrostatic precipitator is to collect particulate matters, and the plasma reactor plays an important role in decomposing organic compounds and precharging particulate matters in order that they may easily be collected in the following electrostatic precipitator. For the performance test of the air cleaner, toluene, trichloroethylene (TCE), n-butanol and methanol were added to the indoor air. According to the experimental data, the collection efficiency of particulate matters was found to be largely enhanced when the plasma reactor was operated. This enhancement of collection efficiency is believed to result from precharging particulate matters. A large amount of electrical energy was required for the decomposition of the organic compounds, which indicates that the indoor air should be repeatedly circulated for proper treatment.

교류 유전체 방전 공정에 의한 휘발성유기화합물 분해 및 전력공급에 관한 연구

목영선,이호원,현영진 제주대학교 해양과환경연구소 2001 해양과환경연구소 연구논문집 Vol.25 No.-

Dielectric barrier discharge reactor packed with glass beads or scoria was utilized for decomposition of volatile organic compounds including benzene, toluene, trichloroethylene, n-butanol and chloroform. Glass beads of 4 to 6 mm in diameter and scoria of 4.75-6.7 mm were used as the dielectric packing materials. The effects of the dielectric packing materials, the gas composition, the applied voltage, and the polarity of the voltage on the decomposition and the power delivery were examined. Filling of the dielectric materials such as glass beads and scoria in the reactor gave rise to the increase in the decomposition of the organic compounds and the discharge power. In spite of the adsorption capability, the scoria showed similar decomposition performance to the glass beads, which indicates that the adsorption capability does not significantly affect the decomposition in steady state condition. In the absence of the dielectric packing material, higher voltage was required to decompose the organic compounds. The gas composition did not largely influence the decomposition efficiency of the organic compounds. When the AC voltage was rectified to positive or negative half-wave, the discharge power and the decomposition efficiency greatly decreased. The power transfer efficiency from the wall plug to the reactor was found to be a strong function of the applied voltage, and a weak function of the gas composition.

마이크로웨이브 플라즈마 공정에 의한 휘발성유기화합물의 분해에 관한 연구

목영신,강호철,이호원 濟州大學校 海洋硏究所 2002 해양과환경연구소 연구논문집 Vol.26 No.-

A microwave plasma system using 2.45 GHz magnetron was applied to the decomposition of volatile organic compounds such as toluene and trichloroethylene. This microwave plasma system designed for producing plasma at atmospheric pressure consists of a magnetron detached from a household microwave oven, a directional coupler, a three-stub tuner, a tapered waveguide, and plasma flame section where a quartz tube with a nozzle is located. In this system, the organic compounds can be decomposed in the way of thermal incineration as well as by the reactions with various active species formed during plasma discharge. The effect of feed gas flow rate on the decomposition was significant due to the decrease in the gas temperature, but the initial concentration in the range of 210-2,100 ppm did not largely affect the decomposition efficiency. The principal byproduct was nitrogen oxides because this system was operated at high temperature. To improve the decomposition of the organic compounds, argon was used as a plasma-assisiting gas, together with the air-like feed gas mixture. Large enhancement in the decomposition efficiency was achieved by the use of argon.

Rat의 복강내에 투여한 5-fluorouracil-polyglycolic acid 제형이 장기에 미치는 영향에 관한 연구

강대영,송규상,최정목,노승무,정경수,오정연,김진향,양준묵,최선웅,이진호,조준식,민병무,김용백,김창식,박근성,김승영,김학용,인현빈 충남대학교 의과대학 지역사회의학연구소 1998 충남의대잡지 Vol.25 No.1

For more effective intraperitoneal chemotherapy, the authers made 5-fluorouracil-polyglycolic acid composite disks(FU-PGA disks) with 5-fluorouracil and polyglycolic acid, a biodegradable polymer. We inserted the FU-PGA disk into the peritoneal cavites of Sprague-Dawley male rats, the control and three experimental groups; one FU-PGA disk insert group(300mg/kg), two FU-PGA disk insert group(600mg/kg), and three FU-PGA disk insert group(900mg/kg). The control group received a similar number of PGA disk inserts. A pharmacokinetic study was performed to measure the 5-fluorouracil concentration in the peritoneal fluid, blood, and tissues(liver, kidney and heart) at 24 hours, 72hours and 168 hours after insertion of the FU-PGA disk. Light and electron microscopic studies were done. The results were as follows: 1) The number of white blood cells and platelets decreased after FU-PGA insertion. The degree was proportional to the duration and amounts inserted. The change in the number of red blood cells varied slightly. 2) Light microscopically, slight changes were noted at 168 hours in the 3 disk insert group (900mg/kg). Mild fatty change and hepatocyte degeneration around the central veins of the liver were noted, with vacuolar degeneration in the proximal convoluted tubules of the kidney. 3) Electron microscopically,the liver showed focal increases of lipid droplets in the hepatocytes, and irregular nuclear membrane with focal nucleolar segregation of the fibrillar and granular elements. Also the double membranous structure of the hepatocytes and Kupffer cells was widened with bleb formation. The kidney showed wide separation of the nuclear double membrane in the proximal convoluted tubular cells and mesangial cells, with vacuolation and myelin figure formation in the mitochondria of the proximal convoluted tubular cells, at 72 hours and 168 hours in the 2 to 3 FU-PGA insert groups. The heart showed focal loss of cristae,vacuolation and myelin figure formation in the mitochondria of the 2 to 3 FU-PGA insert groups. In conclusion, despite the large amont of FU-PGA inserted, the histopathological changes in the liver, kidney and heart were slight, and consonant with the very low amount of 5-fluorouracil concentrations detected in the liver, kidney and heart. The above results suggest that the FU-PGA composite can serve as a new device for releasing drugs in a controlled manner and easily targeted to intraperitoneal organs. This device can improve the efficacy of intraperitoneal chemotherapy for gastric cancer.