• Title/Summary/Keyword: PI4P

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Ginsenoside Rg3-enriched red ginseng extract inhibits platelet activation and in vivo thrombus formation

  • Jeong, Dahye;Irfan, Muhammad;Kim, Sung-Dae;Kim, Suk;Oh, Jun-Hwan;Park, Chae-Kyu;Kim, Hyun-Kyoung;Rhee, Man Hee
    • Journal of Ginseng Research
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    • v.41 no.4
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    • pp.548-555
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    • 2017
  • Background: Korean Red Ginseng has been used for several decades to treat many diseases, enhancing both immunity and physical strength. Previous studies have documented the therapeutic effects of ginseng, including its anticancer, antiaging, and anti-inflammatory activities. These activities are mediated by ginsenosides present in the ginseng plant. Ginsenoside Rg3, an effective compound from red ginseng, has been shown to have antiplatelet activity in addition to its anticancer and anti-inflammatory activities. Platelets are important for both primary hemostasis and the repair of the vessels after injury; however, they also play a crucial role in the development of acute coronary diseases. We prepared ginsenoside Rg3-enriched red ginseng extract (Rg3-RGE) to examine its role in platelet physiology. Methods: To examine the effect of Rg3-RGE on platelet activation in vitro, platelet aggregation, granule secretion, intracellular calcium ($[Ca^{2+}]_i$) mobilization, flow cytometry, and immunoblot analysis were carried out using rat platelets. To examine the effect of Rg3-RGE on platelet activation in vivo, a collagen plus epinephrine-induced acute pulmonary thromboembolism mouse model was used. Results: We found that Rg3-RGE significantly inhibited collagen-induced platelet aggregation and $[Ca^{2+}]_i$ mobilization in a dose-dependent manner in addition to reducing ATP release from collagen-stimulated platelets. Furthermore, using immunoblot analysis, we found that Rg3-RGE markedly suppressed mitogen-activated protein kinase phosphorylation (i.e., extracellular stimuli-responsive kinase, Jun N-terminal kinase, p38) as well as the PI3K (phosphatidylinositol 3 kinase)/Akt pathway. Moreover, Rg3-RGE effectively reduced collagen plus epinephrine-induced mortality in mice. Conclusion: These data suggest that ginsenoside Rg3-RGE could be potentially be used as an antiplatelet therapeutic agent against platelet-mediated cardiovascular disorders.

Relationships between osteoporosis, alveolar bone density and periodontal disease in postmenopausal women (골다공증과 악골의 골밀도 및 치주 질환과의 상관 관계)

  • Han, E.Y.;Rhyu, I.C.;Lee, Y.M.;Ku, Y.;Han, S.B.;Choi, S.M.;Shin, J.Y.;Yang, S.M.;Chung, C.P.
    • Journal of Periodontal and Implant Science
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    • v.31 no.3
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    • pp.565-571
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    • 2001
  • The purpose of this study is to determine if a relationship exists among osteoporosis, alveolar bone density and periodontal disease in postmenopausal osteoporotic women and postmenopausal healthy women. Twenty-two women were evaluated for this study. They were attending the postmenopausal clinic, Seoul National University Hospital and generally healthy except osteoporosis. They had experienced menopause not less than one year when we began to examine them. Bone densities of lumbar area(L2-L4) was determined by DEXA(LUNAR-expert Co,. U.S.A). We diagnosed osteoporosis when T-score was below -2.5 and healthy state when T-score was over -1. Osteoporotic(10 female), not hormone-treated group and healthy control group(12 female) were asked for their age, menopausal age, menopausal period and the number of remaining teeth and examined clinically for plaque index(PI), gingival index(GI), clinical attachment loss(CAL) on their 6 Ramfjord index teeth. Intraoral radiographs were taken in maxillary anterior zone. All films were equally exposed and developed. Each films was digitized and analysed using image processing software, Scion image. Alveolar bone regions of interest were selected and Intensity of each pixel was quantized in the array ranging from 0(white) to 255(black). The two groups were comparable with respect age, menopausal age, menopausal period and number of remaining teeth. The osteoporotic women had significantly lower alveolar bone density than controls in maxilla. But no significant difference was found with respect clinical attachment loss, plaque index and gingival index. Supported by the Ministry of Public Health and Welfare, Korea (HMP-00-CH-10-0009).

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Novel Isoquinolinamine and Isoindoloquinazolinone Compounds Exhibit Antiproliferative Activity in Acute Lymphoblastic Leukemia Cells

  • Roolf, Catrin;Saleweski, Jan-Niklas;Stein, Arno;Richter, Anna;Maletzki, Claudia;Sekora, Anett;Escobar, Hugo Murua;Wu, Xiao-Feng;Beller, Matthias;Junghanss, Christian
    • Biomolecules & Therapeutics
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    • v.27 no.5
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    • pp.492-501
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    • 2019
  • Nitrogen-containing heterocycles such as quinoline, quinazolinones and indole are scaffolds of natural products and have broad biological effects. During the last years those structures have been intensively synthesized and modified to yield new synthetic molecules that can specifically inhibit the activity of dysregulated protein kinases in cancer cells. Herein, a series of newly synthesized isoquinolinamine (FX-1 to 8) and isoindoloquinazolinone (FX-9, FX-42, FX-43) compounds were evaluated in regards to their anti-leukemic potential on human B- and T- acute lymphoblastic leukemia (ALL) cells. Several biological effects were observed. B-ALL cells (SEM, RS4;11) were more sensitive against isoquinolinamine compounds than T-ALL cells (Jurkat, CEM). In SEM cells, metabolic activity decreased with $10{\mu}M$ up to 26.7% (FX-3), 25.2% (FX-7) and 14.5% (FX-8). The 3-(p-Tolyl) isoquinolin-1-amine FX-9 was the most effective agent against B- and T-ALL cells with IC50 values ranging from 0.54 to $1.94{\mu}M$. None of the tested compounds displayed hemolysis on erythrocytes or cytotoxicity against healthy leukocytes. Anti-proliferative effect of FX-9 was associated with changes in cell morphology and apoptosis induction. Further, influence of FX-9 on PI3K/AKT, MAPK and JAK/STAT signaling was detected but was heterogeneous. Functional inhibition testing of 58 kinases revealed no specific inhibitory activity among cancer-related kinases. In conclusion, FX-9 displays significant antileukemic activity in B- and T-ALL cells and should be further evaluated in regards to the mechanisms of action. Further compounds of the current series might serve as templates for the design of new compounds and as basic structures for modification approaches.

Effect of substrate bias voltage on a-C:H film (기판 bias 전압이 a-C:H 박막의 특성에 미치는 영향)

  • 유영조;김효근;장홍규;오재석;김근식
    • Journal of the Korean Vacuum Society
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    • v.6 no.4
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    • pp.348-353
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    • 1997
  • Hydrogenated amorphous carbon(a-C:H) films were deposited on p-type Si(100) by DC saddle-field plasma enhanced CVD to investigate the effect of substrate bias on optical properties and structural changes. They were deposited using pure methane gas at a wide range of substrate bias at room temperature and 90 mtorr. The substrate bias voltage ($V_s$) was employed from $V_s=0 V$ to $V_s=400 V$. The information of optical properties was investigated by photoluminescence and transmitance. Chemical bondings of a-C:H have been explored from FT-IR and Raman spectroscopy. The thickness and relative hydrogen content of the films were measured by Rutherford backscattering spectroscopy (RBS) and elastic recoil detection (ERD) technigue. The growth rate of a-C:H film was decreased with the increase of $V_s$, but the hydrogen content of the film was increased with the increase of $V_s$. The a-C:H films deposited at the lowest $V_s$ contain the smallest amount of hydrogen with most of C-H bonds in the of $CH_2$ configuration, whereas the films produced at higher $V_s$ reveal dominant the $CH_3$ bonding structure. The emission of white photoluminescence from the films were observed even with naked eyes at room temperature and the PL intensity of the film has the maximum value at $V_s$=200 V. With $V_s$ lower than 200 V, the PL intensity of the film increased with V, but for V, higher than 200 V, the PL intensity decreased with the increase of $V_s$. The peak energy of the PL spectra slightly shifted to the higher energy with the increase of $V_s$. The optical bandgap of the film, determined by optical transmittance, was increased from 1.5 eV at $V_s$=0V to 2.3 eV at $V_s$=400 V. But there were no obvious relations between the PL peak and the optical gap which were measured by Tauc process.

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Radiation Response Modulation of GW572016 (EGFR/HER2 Dual Tyrosine Kinase Inhibitor) in Human Breast Cancer Xenografts (인간 유방암 세포 이식마우스에서 EGFR/HER2 복합 Tyrosine Kinase 억제제인 GW572016에 의한 방사선증진효과)

  • Kim, Yeon-Sil;Roh, Kwang-Won;Chae, Soo-Min;Mun, Seong-Kwon;Yoon, Sei-Chul;Jang, Hong-Seok;Chung, Su-Mi
    • Radiation Oncology Journal
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    • v.25 no.4
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    • pp.233-241
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    • 2007
  • Purpose: We examined the effect of the dual EGFR/HER2 tyrosine kinase inhibitor, GW572016, on EGFR/HER2 receptor phosphorylation, inhibition of downstream signaling and radiosensitization in either an EGFR or HER2 overexpressing human breast cancer xenograft. Materials and Methods: We established SCID mice xenografts from 4 human breast cancer cell line that overexpressed EGFR or HER 2 (SUM 102, SUM 149, SUM 185, SUM 225). Two series of xenografts were established. One series was established for determining inhibition of the EGFR/HER2 receptor and downstream signaling activities by GW572016. The other series was established for determining the radiosensitization effect of GW572016. Inhibition of the receptor and downstream signaling proteins were measured by the use of immunoprecipitation and Western blotting. For determining the in vivo radiosensitization effect of GW572016, we compared tumor growth delay curves in the following four treatment arms: a) control; b) GW572016 alone; c) radiotherapy (RT) alone; d) GW572016 and RT. Results: GW572016 inhibited EGFR, HER2 receptor phosphorylation in SUM 149 and SUM 185 xenografts. In addition, the p44/42 MAPK (ERK 1/2) downstream signaling pathway was inactivated by GW572016 in the SUM 185 xenograft. In the SUM 225 xenograft, we could not observe inhibition of HER2 receptor phosphorylation by GW572016; both p44/42 MAPK (Erk1/2) and Akt downstream signal protein phosphorylation were inhibited by GW572016. GW572016 inhibited growth of the tumor xenograft of SUM 149 and SUM 185. The combination of GW572016 and RT enhanced growth inhibition greater than that with GW572016 alone or with RT alone in the SUM 149 xenograft. GW572016 appears to act as an in vivo radiosensitizer. Conclusion: GW572016 inhibited EGFR/HER2 receptor phosphorylation and downstream signaling pathway proteins. GW572016 modestly inhibited the growth of tumor in the SUM 185 xenograft and showed radiosensitization in the SUM 149 xenograft. Our results suggest that a better predictor of radiation response would be inhibition of a crucial signaling pathway than inhibition of a receptor.

A Stochastic Study for the Emergency Treatment of Carbon Monoxide Poisoning in Korea (일산화탄소중독(一酸化炭素中毒)의 진료대책(診療對策) 수립(樹立)을 위한 추계학적(推計學的) 연구(硏究))

  • Kim, Yong-Ik;Yun, Dork-Ro;Shin, Young-Soo
    • Journal of Preventive Medicine and Public Health
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    • v.16 no.1
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    • pp.135-152
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    • 1983
  • Emergency medical service is an important part of the health care delivery system, and the optimal allocation of resources and their efficient utilization are essentially demanded. Since these conditions are the prerequisite to prompt treatment which, in turn, will be crucial for life saving and in reducing the undesirable sequelae of the event. This study, taking the hyperbaric chamber for carbon monoxide poisoning as an example, is to develop a stochastic approach for solving the problems of optimal allocation of such emergency medical facility in Korea. The hyperbaric chamber, in Korea, is used almost exclusively for the treatment of acute carbon monoxide poisoning, most of which occur at home, since the coal briquette is used as domestic fuel by 69.6 per cent of the Korean population. The annual incidence rate of the comatous and fatal carbon monoxide poisoning is estimated at 45.5 per 10,000 of coal briquette-using population. It offers a serious public health problem and occupies a large portion of the emergency outpatients, especially in the winter season. The requirement of hyperbaric chambers can be calculated by setting the level of the annual queueing rate, which is here defined as the proportion of the annual number of the queued patients among the annual number of the total patients. The rate is determined by the size of the coal briquette-using population which generate a certain number of carbon monoxide poisoning patients in terms of the annual incidence rate, and the number of hyperbaric chambers per hospital to which the patients are sent, assuming that there is no referral of the patients among hospitals. The queueing occurs due to the conflicting events of the 'arrival' of the patients and the 'service' of the hyperbaric chambers. Here, we can assume that the length of the service time of hyperbaric chambers is fixed at sixty minutes, and the service discipline is based on 'first come, first served'. The arrival pattern of the carbon monoxide poisoning is relatively unique, because it usually occurs while the people are in bed. Diurnal variation of the carbon monoxide poisoning can hardly be formulated mathematically, so empirical cumulative distribution of the probability of the hourly arrival of the patients was used for Monte Carlo simulation to calculate the probability of queueing by the number of the patients per day, for the cases of one, two or three hyperbaric chambers assumed to be available per hospital. Incidence of the carbon monoxide poisoning also has strong seasonal variation, because of the four distinctive seasons in Korea. So the number of the patients per day could not be assumed to be distributed according to the Poisson distribution. Testing the fitness of various distributions of rare event, it turned out to be that the daily distribution of the carbon monoxide poisoning fits well to the Polya-Eggenberger distribution. With this model, we could forecast the number of the poisonings per day by the size of the coal-briquette using population. By combining the probability of queueing by the number of patients per day, and the probability of the number of patients per day in a year, we can estimate the number of the queued patients and the number of the patients in a year by the number of hyperbaric chamber per hospital and by the size of coal briquette-using population. Setting 5 per cent as the annual queueing rate, the required number of hyperbaric chambers was calculated for each province and for the whole country, in the cases of 25, 50, 75 and 100 per cent of the treatment rate which stand for the rate of the patients treated by hyperbaric chamber among the patients who are to be treated. Findings of the study were as follows. 1. Probability of the number of patients per day follows Polya-Eggenberger distribution. $$P(X=\gamma)=\frac{\Pi\limits_{k=1}^\gamma[m+(K-1)\times10.86]}{\gamma!}\times11.86^{-{(\frac{m}{10.86}+\gamma)}}$$ when$${\gamma}=1,2,...,n$$$$P(X=0)=11.86^{-(m/10.86)}$$ when $${\gamma}=0$$ Hourly arrival pattern of the patients turned out to be bimodal, the large peak was observed in $7 : 00{\sim}8 : 00$ a.m., and the small peak in $11 : 00{\sim}12 : 00$ p.m. 2. In the cases of only one or two hyperbaric chambers installed per hospital, the annual queueing rate will be at the level of more than 5 per cent. Only in case of three chambers, however, the rate will reach 5 per cent when the average number of the patients per day is 0.481. 3. According to the results above, a hospital equipped with three hyperbaric chambers will be able to serve 166,485, 83,242, 55,495 and 41,620 of population, when the treatmet rate are 25, 50, 75 and 100 per cent. 4. The required number of hyperbaric chambers are estimated at 483, 963, 1,441 and 1,923 when the treatment rate are taken as 25, 50, 75 and 100 per cent. Therefore, the shortage are respectively turned out to be 312, 791. 1,270 and 1,752. The author believes that the methodology developed in this study will also be applicable to the problems of resource allocation for the other kinds of the emergency medical facilities.

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Study of BiJeung by 18 doctors - Study of II - (18인(人)의 비증(痺證) 논술(論述)에 대(對)한 연구(硏究) - 《비증전집(痺證專輯)》 에 대(對)한 연구(硏究) II -)

  • Sohn, Dong Woo;Oh, Min Suk
    • Journal of Haehwa Medicine
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    • v.9 no.1
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    • pp.595-646
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    • 2000
  • I. Introduction Bi(痺) means blocking. BiJeung is one kind of symptoms making muscles, bones and jonts feel pain, numbness or edema. For example it can be gout or SLE etc. says that Bi is combination of PungHanSeup. And many doctors said that BiJeung is caused by food, fatigue, sex, stress and change of weather. Therefore we must treat BiJeung by character of patients and characteristic of the disease. Many famous doctors studied medical science by their fathers or teachers. So the history of medical science is long. So I studied ${\ll}Bijeungjujip{\gg}$. II. Final Decision 1. JoGeumTak(趙金鐸) devided BiJeung into Pung, Han, Seup and EumHeo, HeulHeo, YangHeo, GanSinHeo by charcter or reaction of pain. And he use DaeJinGyoTang, GyegiGakYakJiMoTang, SamyoSan, etc. 2. JangPaeGyeu(張沛圭) focused on division of HanYeol(寒熱; coldness and heat) in spite of complexity of BiJeung. He also used insects for treatment. They are very useful for treatment of BiJeung because they can remove EoHyeol(瘀血). 3. SeolMaeng(薛盟) said that the actual cause of BiJeung is Seup. So he thought that BiJeung can be divided into PungSeup, SeupYeol, HanSeup. And he established 6 rules to treat BiJeung and he studied herbs. 4. JangGi(張琪) introduced 10 prescriptions and 10 rules to cure BiJeung. The 1st prescription is for OyeSa, 2nd for internal Yeol, 3rd for old BiJeung, 4th for Soothing muscles, 5th for HanSeup, 6th for regular BiJeung, 7th for functional disorder, 8th for YeolBi, 9th for joint pain and 10th for pain of lower limb. 5. GangSeYoung(江世英) used PungYeongTang(風靈湯) for the treatment of PungBi, OGyeHeukHoTang(烏桂黑虎湯) for HanBi, BangGiMokGwaTang(防己木瓜湯) for SeupBi, YeolBiTang(熱痺湯) for YeolBi, WoDaeRyeokTang(牛大力湯) for GiHei, HyeolPungGeunTang(血楓根湯) for HyeolHeo, ToJiRyongTang(土地龍湯) for the acute stage of SeupBi, OJoRyongTang(五爪龍湯) for the chronic stage of SeupBi, and so on. 6. ShiGeumMook(施今墨) devided BiJeung into four types. They are PungSeupYeol, PungHanSeup, GiHyeolSil(氣血實) and GiHyeolHeo(氣血虛). And he introduced the eight rules of the treatment(SanPun(散風), ChukHan(逐寒), GeoSeuP(, CheongYeol(淸熱), TongRak(通絡), HwalHyeol(活血), HaengGi(行氣), BoHeo(補虛)). 7. WangYiYou(王李儒) explained the acute athritis and said that it can be applicable to HaneBi(行痺). And he used GyeJiJakYakJiMoTang(桂枝芍蘂知母湯) for HanBi and YeolBiJinTongTang(熱痺鎭痛湯) for YeolBi. 8. JangJinYeo(章眞如) said that YeolBi is more common than HanBi. The sympthoms of YeolBi are severe pain, fever, dried tongue, insomnia, etc. And he devided YeolBi into SilYeol and HeoYeol. In case of SilYeol, he used GyeoJiTangHapBaekHoTang(桂枝湯合白虎湯) and in case of HeoYeol he used JaEumYangAekTang(滋陰養液湯). 9. SaHaeJu(謝海洲) introduced three important rules of treatment and four appropriate rules of treatment of BiJeung. 10. YouDoJu(劉渡舟) said that YeolBi is more common than HanBi. He used GaGamMokBanGiTang(加減木防已湯) for YeolBi, GyeJiJakYakJiMoTang or GyeJiBuJaTang(桂枝附子湯) for HanBi and WooHwangHwan(牛黃丸) for the joint pain. 11. GangYiSon(江爾遜) focused on the internal cause. The most important internal cause is JeongGiHeo(正氣虛). So he tried to treat BiJeung by means of balance of Gi and Hyeol. So he ususlly used ODuTang(烏頭湯) and SamHwangTang(三黃湯) for YeolBi, OJeokSan(五積散) for HanBi, SamBiTang(三痺湯) for the chronic BiJeung. 12. HoGeonHwa(胡建華) said that to distinguish YeolBi from Hanbi is very difficult. So he used GyeJiJakYakJiMoTang in case of mixture of HanBi and YeoBi. 13. PiBokGo(畢福高) said that the most common BiJeung is HanBi. He usually used acupuncture with medicine. He followed the theory of EumYongHwa(嚴用和)-he focused on SeonBoHuSa(先補後瀉). 14. ChoiMunBin(崔文彬) used GeoPungHwalHyeolTang(祛風活血湯) for HanBi, SanHanTongRakTang(散寒通絡湯) for TongBi(痛痺), LiSeupHwaRakTang(利濕和絡湯) for ChakBi(着痺), CheongYeolTongGyeolChukBiTang(淸熱通經逐痺湯) for YeolBi(熱痺) and GeoPungHwalHyeolTang(祛風活血湯) for PiBi(皮痺). 15. YouleokSeon(劉赤選) introduced the common principle for the treatment of BiJeung. He used HaePuneDeungTang(海風藤湯) for HaengBi(行痺), SinChakTang(腎着湯), DokHwalGiSaengTang(獨活寄生湯) for TongBi(痛痺), TongPungBang(痛風方) for ChakBi(着痺) and SangGiYiMiTangGaYeongYangGakTang(桑枝苡米湯加羚羊角骨) for YeolBi(熱痺). 16. LimHakHwa(林鶴和) said about TanTan(movement disorders or numbness) and devided TanTan into the acute stage and the chronic stage. He used acupuncture at the meridian spot like YeolGyeol(列缺), HapGok(合谷), etc. And he also used MaHwangBuJaSeSinTang(麻黃附子細辛湯) in case of the acute stage. In the chronic stage he used BangPungTang(防風湯). 17. JinBaekGeun(陳伯勤) liked to use three rules(HwaHyeol(活血), ChiDam(治痰), BoSin(補腎)) to treat BiJeung. He used JinTongSan(鎭痛散) for the purpose of HwalHyeol(活血), SoHwalRakDan(小活絡丹) for ChiDam(治痰) and DokHwalGiSaengTang(獨活寄生湯) for BoSin(補腎). 18. YimGyeHak(任繼學) focused on YangHyeolJoGi(養血調氣) if the stage of BiJeung is chronic. And in the chronic stage he insisted on not using GalHwal(羌活), DokHwal(獨活) and BangPung(防風).

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Nitrogen Removal Rate of A Subsurface Flow Treatment Wetland System Constructed on Floodplain During Its Initial Operating Stage (하천고수부지 수질정화 여과습지의 초기운영단계 질소제거)

  • Yang, Hong-Mo
    • Korean Journal of Environmental Agriculture
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    • v.22 no.4
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    • pp.278-283
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    • 2003
  • This study was carried out to examine the nitrogen removal rate of a subsurface-flow treatment wetland system which was constructed on floodplain of the Kwangju River from May to June 2001. Its dimensions were 29m in length, 9m in width and 0.65m in depth. A bottom layer of 45cm in depth was filled with crushed granite with about $15{\sim}30\;mm$ in diameter and a middle layer of 10cm in depth had pea pebbles with about 10 mm in diameter. An upper layer of 5 cm in depth contained course sand. Reeds (Phragmites australis) were transplanted on the surface of the system. They were dug out of natural wetlands and stems were cut at about 40 cm height from their bottom ends. Water of the Kwangju River flowed into it via a pipe by gravity flow and its effluent was funneled back into the river. The height of reed stems was 44.2 cm in July 2001 and 75.3cm in September 2001. The number of stems was increased from $80\;stems/m^2$ in July 2001 to $136\;stems/m^2$ in September 2001. Volume and water quality of inflow and outflow were analyzed from July 2001 through December 2001. Inflow and outflow averaged 40.0 and $39.2\;m^3/day$, respectively. Hydraulic detention time was about 1.5 days. Average nitrogen uptake by reeds was $69.31\;N\;mg/m^2/day$. Removal rate of $NO_3-N$, $NH_3-N$, T-N averaged 195.58, 53.65, and $628.44\;mg/m^2/day$, respectively. Changes of $NO_3-N$ and $NH_3-N$ abatement rates were closely related to those of wetland temperatures. The lower removal rate of nitrogen species compared with that of subsurface-flow wetlands operating in North America could be attributed to the initial stage of the system and inclusion of two cold months into the six-month monitoring period. Increase of standing density of reeds within a few years will develop both root zones suitable for the nitrification of ammonia and surface layer substrates beneficial to the denitrification of nitrates into nitrogen gases, which may lead to increment in the nitrogen retention rate.