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In vitro and in vivo Antibacterial Activities and Pharmacokinetics of 8-Fluorociprofloxacin and Ciprofloxacin (8-Fluorociprofloxacin과 Ciprofloxacin의 시험관내 및 생체내 항균효과와 약물동태의 비교)

  • 최경업;정용환;김제학
    • YAKHAK HOEJI
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    • v.37 no.3
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    • pp.235-242
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    • 1993
  • 8-Fluorociprofloxacin(8-FCP) is an investigational quinolone derivative that is substituted with fluorine at the C-8 position of ciprofloxacin(CP). It was found that the in vitro activity of 8-FCP against Gram(+) bacteria was more potent that of CP, but the opposite against Gram(-) bacteria was true. However, 8-FCP showed better in vivo efficacy than CP against representative Gram(-) organisms, E. coli and K pneumoniae. In an attempt to seek for factors causing this discrepancy in the antibacterial activities, a comparative pharmacokinetic study of 8-FCP and CP was conducted in mice and rats treated either intravenously or orally at a single dose of 30 mg/kg. The pharmacokinetic parameters in mice were as follows; the mean peak serum concentrations(C$_{max}$) following i.v. and oral doses were 12.4 and 5.3 $\mu\textrm{g}$/ml for 8-FCP, and 9.5 and 2.5 $\mu\textrm{g}$/ml for CP, respectively. The terminal half-life(t$_{1/2\beta}$) was 72.9 min for 8-FCP, and 98.2 min for CP, and the oral bioavailability(F) was 89.9% for 8-FCP, and 50.5% for CP. In rats, the mean ($\pm$SD) $C_{max}$ after i.v. administration were 11.6$\pm$1.6 $\mu\textrm{g}$/ml for 8-FCP, and 10.2$\pm$1.3 $\mu\textrm{g}$/ml for CP, whereas oral administration produced $C_{max}$ of 5.9$\pm$1.8 $\mu\textrm{g}$/ml for 8-FCP and 1.1$\pm$0.9 $\mu\textrm{g}$/ml for CP, respectively. The t$_{1/2\beta}$ was 67.9$\pm$8.4 min for 8-FCP, and 76.4$\pm$7.2 min for CP. The F was 88.6$\pm$6.3% for 8-FCP, and 40.7$\pm$6.5% for CP. Marked differences were observed between the two quinolones in the $C_{max}$ and the area under the concentration-time curve obtained after oral administration in mice and rats. The extent of 8-FCP absorption in both mice and rats was approximately 2-fold higher than that of CP, suggesting that the fluorine atom attached to C-8 plays an important role in facilitating oral absorption from the gastrointestinal tract.

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Beneficial effects of fermented black ginseng and its ginsenoside 20(S)-Rg3 against cisplatin-induced nephrotoxicity in LLC-PK1 cells

  • Han, Myoung-Sik;Han, Im-Ho;Lee, Dahae;An, Jun Min;Kim, Su-Nam;Shin, Myoung-Sook;Yamabe, Noriko;Hwang, Gwi Seo;Yoo, Hye Hyun;Choi, Suk-Jung;Kang, Ki Sung;Jang, Hyuk-Jai
    • Journal of Ginseng Research
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    • v.40 no.2
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    • pp.135-140
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    • 2016
  • Background: Nephrotoxicity is a common side effect of medications. Panax ginseng is one of the best-known herbal medicines, and its individual constituents enhance renal function. Identification of its efficacy and mechanisms of action against drug-induced nephrotoxicity, as well as the specific constituents mediating this effect, have recently emerged as an interesting research area focusing on the kidney protective efficacy of P. ginseng. Methods: The present study investigated the kidney protective effect of fermented black ginseng (FBG) and its active component ginsenoside 20(S)-Rg3 against cisplatin (chemotherapy drug)-induced damage in pig kidney (LLC-PK1) cells. It focused on assessing the role of mitogen-activated protein kinases as important mechanistic elements in kidney protection. Results: The reduced cell viability induced by cisplatin was significantly recovered with FBG extract and ginsenoside 20(S)-Rg3 dose-dependently. The cisplatin-induced elevated protein levels of phosphorylated c-Jun N-terminal kinase (JNK), p53, and cleaved caspase-3 were decreased after cotreatment with FBG extract or ginsenoside 20(S)-Rg3. The elevated percentage of apoptotic LLC-PK1 cells induced by cisplatin treatment was significantly abrogated by cotreatment with FBG and the ginsenoside 20(S)-Rg3. Conclusion: FBG and its major ginsenoside 20(S)-Rg3, ameliorated cisplatin-induced nephrotoxicity in LLC-PK1 cells by blocking the JNKep53ecaspase-3 signaling cascade.

Hydrogen Peroxide- and Nitric Oxide-mediated Disease Control of Bacterial Wilt in Tomato Plants

  • Hong, Jeum Kyu;Kang, Su Ran;Kim, Yeon Hwa;Yoon, Dong June;Kim, Do Hoon;Kim, Hyeon Ji;Sung, Chang Hyun;Kang, Han Sol;Choi, Chang Won;Kim, Seong Hwan;Kim, Young Shik
    • The Plant Pathology Journal
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    • v.29 no.4
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    • pp.386-396
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    • 2013
  • Reactive oxygen species (ROS) generation in tomato plants by Ralstonia solanacearum infection and the role of hydrogen peroxide ($H_2O_2$) and nitric oxide in tomato bacterial wilt control were demonstrated. During disease development of tomato bacterial wilt, accumulation of superoxide anion ($O_2{^-}$) and $H_2O_2$ was observed and lipid peroxidation also occurred in the tomato leaf tissues. High doses of $H_2O_2$ and sodium nitroprusside (SNP) nitric oxide donor showed phytotoxicity to detached tomato leaves 1 day after petiole feeding showing reduced fresh weight. Both $H_2O_2$ and SNP have in vitro antibacterial activities against R. solanacearum in a dose-dependent manner, as well as plant protection in detached tomato leaves against bacterial wilt by $10^6$ and $10^7$ cfu/ml of R. solanacearum. $H_2O_2$- and SNP-mediated protection was also evaluated in pots using soil-drench treatment with the bacterial inoculation, and relative 'area under the disease progressive curve (AUDPC)' was calculated to compare disease protection by $H_2O_2$ and/or SNP with untreated control. Neither $H_2O_2$ nor SNP protect the tomato seedlings from the bacterial wilt, but $H_2O_2$ + SNP mixture significantly decreased disease severity with reduced relative AUDPC. These results suggest that $H_2O_2$ and SNP could be used together to control bacterial wilt in tomato plants as bactericidal agents.

Human Lung Insults due Air Pollutant -A Review for Priority Setting in the Research- (대기오염에 의한 폐장조직 손상 -연구방향의 설정을 위한 논의-)

  • 김건열;백도명
    • Journal of environmental and Sanitary engineering
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    • v.7 no.2
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    • pp.95-110
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    • 1992
  • Much progress has been made in understanding the subcellular events of the human lung injuries after acute exposure to environmental air pollutants. Host of those events represent oxidative damages mediated by reactive oxygen species such as superoxide, hydrogen peroxide, and the hydroxy, free radical. Recently, nitric oxide (NO) was found to be endogenously produced by endothelial cells and cells of the reticulo-endothelial system as endothelialderived relaxation factor (EDRF) which is a vasoactive and neurotransmitter substance. Together with superoxide, NO can form another strong oxidant, peroxonitrite. The relative importance of exogenous sources of $N0/N0_2$ and endogenous production of NO by the EDRF producing enzymes in the oxidative stresses to the heman lung has to be elucidated. The exact events leading to chronic irreversible damage are still yet to be known. From chronic exposure to oxidant gases, progressive epithelial and interstitial damages develop. Type I epithelial cells become thicker and cover a smaller average alveolar surface area while thee II cells proliferate instead. Under acute damages, the extent of loss of the alveolar epithelial cell lining, especially type II cells appears to be a good predictor of the ensuing irreversible damage to alveolar compartment. Interstitial matrix undergo remodeling during chronic exposure with increased collagen fibers and interstitial fibroblasts. However, Inany of these changes can be reversed after cessation of exposure. Among chronic lung injuries, genetic damages and repair responses received particular attention in view of the known increased lung cancer risks from exposure to several air pollutants. Heavy metals from foundry emission, automobile traffics, and total suspended particulate, especially polycystic aromatic hydrocarbons have been positively linked with the development of lung cancer. Asbestos in another air pollutant with known risk of lung cancer and mesothelioma, but asbestos fibers are nonauthentic in most bioassays. Studies using the electron spin resonance spin trapping method show that the presence of iron in asbestos accelerates the production of the hydroxy, radical in vitro. Interactions of these reactive oxygen species with particular cellular components and disruption of cell defense mechanisms still await further studies to elucidate the carcinogenic potential of asbestos fibers of different size and chemical composition. The distribution of inhaled pollutants and the magnitude of their eventual effects on the respiratory tract are determined by pollutant-independent physical factors such as anatomy of the respiratory tract and level and pattern of breathing, as well as by pollutant-specific phyco-chemical factors such as the reactivity, solubility, and diffusivity of the foreign gas in mucus, blood and tissue. Many of these individual factors determining dose can be quantified in vitro. However, mathematical models based on these factors should be validated for its integrity by using data from intact human lungs.

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Atmospheric Dispersion Assessment for Potential Accidental Releases at Yonggwang Nuclear Power Plants (영광원전에서 가상 사고시 대기확산 평가)

  • Na, Man-Gyun;Sim, Young-Rok;Jung, Chul-Kee;Lee, Goung-Jin;Kim, Soong-Pyung;Chung, Sung-Tai
    • Journal of Radiation Protection and Research
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    • v.25 no.2
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    • pp.81-87
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    • 2000
  • XOQ_DW code is currently used to assess the atmospheric dispersion fur the routine releases of radioactive gaseous effluents at Yonggwang nuclear power plants. This code was developed based on XOQDOQ code and an additional code is required to assess the atmospheric dispersion for potential accidental releases. In order to assess the atmospheric dispersion fer the accidental releases, XOQAR code has been developed by using PAVAN code that is based on Reg. Guide 1.145. The terrain data of XOQ_DW code inputs and the relative concentrations (X/Q) of XOQ_DW code outputs are used as the inputs of the XOQAR code through the interface with XOQ_DW code. By using this code, the maximum values of X/Q at exclusion area and low population zone boundaries except for sea areas were assessed as $1.33{\times}10^{-4}$ and $7.66{\times}10^{-6}$ sec/$m^3$, respectively. Through the development of this code, a rode system is prepared for assessing the atmospheric dispersion for the accidental releases as well as the routine releases. This developed code ran be used for other domestic nuclear power plants by modifying the terrain input data.

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Targeted busulfan and fludarabine-based conditioning for bone marrow transplantation in chronic granulomatous disease

  • Ju, Hee Young;Kang, Hyoung Jin;Hong, Che Ry;Lee, Ji Won;Kim, Hyery;Song, Sang Hoon;Yu, Kyung-Sang;Jang, In-Jin;Park, June Dong;Park, Kyung Duk;Shin, Hee Young;Kim, Joong-Gon;Ahn, Hyo Seop
    • Clinical and Experimental Pediatrics
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    • v.59 no.sup1
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    • pp.57-59
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    • 2016
  • Chronic granulomatous disease (CGD) is a primary immunodeficiency disease caused by impaired phagocytic function. Hematopoietic stem cell transplantation (HSCT) is a definitive cure for CGD; however, the use of HSCT is limited because of associated problems, including transplantation-related mortality and engraftment failure. We report a case of a patient with CGD who underwent successful HSCT following a targeted busulfan and fludarabine reduced-toxicity myeloablative conditioning. Intravenous busulfan was administered once daily for 4 consecutive days (days -8 to -5), and the target area under the curve was $75,000{\mu}g{\cdot}hr/L$. Fludarabine ($40mg/m^2$) was administered once daily for 6 consecutive days from days -8 to -3. Antithymocyte globulin (2.5 mg/kg/day) was administered from days -4 to -2. The patient underwent successful engraftment and did not have any severe toxicity related to the transplantation. Conditioning with a targeted busulfan and fludarabine regimen could provide a better outcome for HSCT in CGD, with close regulation of the busulfan dose.

THE EFFECTS OF THE LOW CALCIUM DIET AND IRRADIATION ON THE MANDIBULAR CONDYLE OF RATS (저칼슘식이와 방사선조사가 백서하악과두에 미치는 영향에 관한 실험적 연구)

  • Ahn Hee-Mun;Lee Sang-Rae
    • Journal of Korean Academy of Oral and Maxillofacial Radiology
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    • v.23 no.1
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    • pp.27-44
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    • 1993
  • This study was performed to investigate the changes of mandibular condyle by low calcium diet and the effects of irradiation on the bone in osteoporotic state. In order to carry out this experiment, 80 seven-week old Sprague-Dawley strain rats weighing about 150 gm were selected and equally divided into one experimental group of 40 rats and one control group with the remainder. The experimental group and the control group were then subdivided into two group and exposed to irradiation. The two irradiation groups received a single dose of 20 Gy on the jaw area only and irradiated with a cobalt-60 teletherapy unit. The rats in the control and experimental groups were serially terminated by fours on the 3rd, the 7th, the 14th, and the 21st day after irradiation. After termination, both sides of the dead rats mandibular condyle were removed and fixed with 10% neutral formalin. The bone mineral density of mandibular condyle was measured by use of dual energy X-ray bone densitometer(model DDX-alpha, Lunn Corp., U. S. A.). The mandibular condyle was radiographed with Hitex HA-80(Hitex Co., Japan). Thereafter, the obtained radiographs were observed, and the mandibular condyle was further decalcified and embedded in paraffin as the general method. The specimen sectioned and stained with hematoxylin-eosin, PAS and Rabbit Anti-Human Tumor Necrosis Factor-a observed by a light microscope. The obtained results were as follows: 1. In the non-irradiated group with the low calcium diet, the bone mineral density of the condyle was markedly decreased after 14 days, and decrease the number of trabeculae of the condyle and resorption of the calcified cartilaginous zone were observed after 3 days. On microscopic observations, the number nd size of trabeculae were decreased after 7 days of experiment. 2. In the irradiated group with the low calcium diet, the bone mineral density of the condyle was markedly decreased after 14 days and resorption of the calcified cartilaginous zone and decrease the number and coarse of the trabeculae of the condyle were observed. These findings were extended rather than in non-irradiated group with low calcium diet. On microscopic observations, many osteoclasts were detected and the number and size of trabeculae were somewhat decreased after 7 days. Also there was degenerative changes of tissues of bone marrow on the 14th day but that condition was restored on the 21st day of experiment. 3. In the irradiated group with normal diet, the bone mineral density of the condyle was somewhat decreased with times and degree of decrease of the number of trabeculae was somewhat larger than in the non-irradiated group with normal diet. On microscopic observations, the tissues of bone marrow were atrophic and degenerative changes but that condition was restored on the 21st day of experiment. 4. In immunocytochemical findings, in the irradiated and non-irradiated groups with low calcium diet, negative or partial positive response to TNF was observed, but positive response in the normal diet groups.

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A Study on Characteristics of Jinsatak(陳士鐸)'s Clinic Theory (진사탁(陳士鐸) 임상 이론의 특징에 관한 연구)

  • Jeong, Kyung-Ho;Kim, Ki-Wook;Park, Hyun-Guk
    • Journal of Korean Medical classics
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    • v.22 no.3
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    • pp.31-51
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    • 2009
  • The characteristics of Jin's ideas on clinic theory can be arranged as follows. 1. Jin emphasized warming and tonifying[溫補] in treatment and the part that shows this the best is the taking care of[調理] the Vital gate[命門], kidney, liver, and spleen. His ideas were based on his understanding of a human life's origin, and was influenced by Seolgi(薛己), Joheon-ga(趙獻可) and Janggaebin(張介賓)'s Vital gate and source Gi theory(元氣說) so scholastically, he has that in common with them but was later criticized by later doctors such as Oksamjon(玉三尊) as an 'literary doctor(文字醫)' who followed the ideas of "Uigwan(醫貫)". 2. The warming and tonifying school[溫補學派], who were influenced by Taoism, said in their theory of disease outbreak[發病學說] that since one must not hurt one's Yin essence and Yang fire [陰精陽火] there is more deficiency than excess, so that was why they used tonifying methods. Jin was also like them and this point of view is universal in internal medicine, gynecology, pediatric medicine and surgery and so on. 3. Jin, who saw the negative form of pulse diagnosis[診脈] emphasized following symptoms over pulse diagnosis using the spirit of ‘finding truth based on truth[實事求是]' in "Maekgyeolcheonmi(脈訣闡微)", but emphasized 'the combination of pulse and symptoms[脈證合參]'. He understood pulse diagnosis as a defining tool for symptoms, and in "Seoksilbirok(石室秘錄)" simplified pulse diagnosis into 10 methods : floating/sunken(浮沉), slow/fast(遲數), large/fine(大小), vacuous/replete(虛實) and slippery/rough(滑澀). 4. Jin used 'large formulas(大方)' a lot that usually featured a large dose, and in " Bonchosinpyeon(本草新編)" he thought of the seven formulas(七方) and ten preparations(十劑) as the standard when using medicine. He did away with old customs and presented a 'new(新)' and 'extra(奇)' point of view. He especially used a lot of Insam(人蔘) when tonifying Gi and Geumeunhwa(金銀花) when treating sores and ulcers. 5. In the area of surgery Jin gave priority to the early finding and treatment of disease with internal treatment[內治] and was against the overuse of acupuncture. However records of surgical measures in a special situation like lung abscesses(肺癰) and liver abscesses(肝癰), and anesthetic measures using 'Manghyeongju(忘形酒)' and 'Singoiyak(神膏異藥)' and opening the abdomen or skull, and organ transplants using a dog's tongue are important data. 6. Jin stated the diseases of Gi and blood broadly. Especially in the principles of treating blood, blood diseases had to be forwarded[順] and Gi regulation[理氣] was the number one priority and stated the following two treatments. First, in "Jeonggiinhyeolpyeon(精氣引血篇)" of volume 6 of "Oegyeongmieon(外經微言)", for the rules for treating blood he stated the pattern identification of finding Gi in blood and blood in Gi. Second, he emphasized Gi regulation(理氣) in blood diseases and stated that the Gi must be tonifyed after finding the source of the loss of blood.

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Study on Health Risk Assessment of Carcinogenic Chemicals in Drinking Water (음용수 중 유해 화학 물질에 대한 위해성 평가에 관한 연구 - I. 발암성 화학 물질을 중심으로 -)

  • Chung, Yong;Shin, Dong-Chun;Kim, Jong-Man;Park, Seong-Eun;Yang, Ji-Yeon;Lee, Ja-Koung;Hwang, Man-Sik;Park, Yeon-Shin
    • Environmental Analysis Health and Toxicology
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    • v.10 no.1_2
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    • pp.1-14
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    • 1995
  • The purpose of this research is to assess the health risk of pollutants in drinking water and recommend the guidelines and management plans for maintaining good quality of drinking water. This study has been funded as a national project for three years from 1992 to 1995. This study(the second year, 1993-1994) was conducted to monitor 32 species of carcinogenic chemicals such as volatile organic compounds(VOCs), polynuclear aromatic hydrocarbons(PAHs), pesticides and heavy metals of drinking water at some area in six cities of Korea, and evaluate health risk due to these chemicals through four main steps of risk assessment in drinking water. In hazard identification, 32 species of carcinogenic chemicals were identified by the US EPA classification system. In the step of exposure assessment, sampling of raw, treated and tap water from the public water supply system had been conducted from 1993 to 1994, and 32 chemicals were analyzed. In dose-response assessment, cancer potencies, unit risk estimates and virtually safe doses of carcinogens were obtained by TOX-RISK (Version 3.1). In risk characterization of detected chemicals, health risk due to carcinogens such as vinyl chloride, carbon tetrachloride, dichloromethane, 1, 2-dichloromethane, chloroform, benzene and arsenic of tap water in several cities exceeded 10$^{-5}$ level. We suggest that non-regulated chemicals which exceed 10$^{-5}$ excess cancer risk level, such as vinyl chloride, carbon tetrachloride and 1, 2-dichloroethane, should be monitored periodically and be regulated by the Drinking Water Management Act, and database for exposure parameter of our own situation should be established.

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Application of Ceramic MF Membrane at the Slow Sand Filtration Process (완속모래여과 공정에서 세라믹 MF 막의 적용)

  • Choi, Kwang-Hun;Park, Jong-Yul;Kim, Su-Han;Kim, Jeong-Sook;Kang, Lim-Seok
    • Journal of Korean Society of Environmental Engineers
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    • v.35 no.12
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    • pp.877-882
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    • 2013
  • The application of ultrafiltration (UF) and microfiltration (MF) membranes has been increased for drinking water purification. The advantages of UF/MF membrane process compared to conventional treatment processes are stable operation under varying feed water quality, smaller construction area, and automatic operation. Most membrane treatment plants are designed with polymeric membranes. Recently, some studies suggested that the process of treating surface water with ceramic membranes is competitive to the application of polymeric membranes. Higher water flux, less frequent cleaning, and much longer lifetime are the advantages of ceramic membrane comparing to polymeric membrane. Therefore, this research focused on the application of ceramic MF membrane pilot plant at the slow sand filtration plant. The ceramic membrane pilot plant has three trains that used raw water and sand filtered water as a feed water, respectively. For optimizing the pilot plant process, the coagulation with PACl coagulant was used as a pretreatment of ceramic membrane process. In addition, CEB (Chemical Enhanced Backwash) process using $H_2SO_4$ and NaOCl was used for 1.5 days, respectively. The experimental results showed that applying the optimum coagulant dose before membrane filtration showed enhancing membrane fluxes for both raw water and sand filtered water. Also, when using raw water as a feed of membrane, minimum fouling rate was 2.173 kPa/cycle with 25 mg/L of PACl and when using sand filtered water, the minimum fouling rate was 0.301 kPa/cycle with 5 mg/L of PACl.