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Inhibitory Effects of Olmesartan on Catecholamine Secretion from the Perfused Rat Adrenal Medulla

  • Lim, Hyo-Jeong;Kim, Sang-Yong;Lim, Dong-Yoon
    • The Korean Journal of Physiology and Pharmacology
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    • v.14 no.4
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    • pp.241-248
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    • 2010
  • The present sutdy aimed to determine whether olmesartan, an angiotensin II (Ang II) type 1 ($AT_1$) receptor blocker, can influence the CA release from the isolated perfused model of the rat adrenal medulla. Olmesartan ($5{\sim}50{\mu}M$) perfused into an adrenal vein for 90 min produced dose- and time-dependent inhibition of the CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (56 mM, a direct membrane-depolarizer), DMPP (100 ${\mu}M$) and McN-A-343 (100 ${\mu}M$). Olmesartan did not affect basal CA secretion. Also, in adrenal glands loaded with olmesartan (15 ${\mu}M$), the CA secretory responses evoked by Bay-K-8644 (10 ${\mu}M$, an activator of voltage-dependent L-type $Ca^{2+}$ channels), cyclopiazonic acid (10 ${\mu}M$, an inhibitor of cytoplasmic $Ca^{2+}$-ATPase), veratridine (100 ${\mu}M$, an activator of voltage-dependent $Na^+$ channels), and Ang II (100 nM) were markedly inhibited. However, at high concentrations ($150{\sim}300{\mu}M$), olmesartan rather enhanced the ACh-evoked CA secretion. Taken together, these results show that olmesartan at low concentrations inhibits the CA secretion evoked by cholinergic stimulation (both nicotininc and muscarinic receptors) as well as by direct membrane depolarization from the rat adrenal medulla, but at high concentrations it rather potentiates the ACh-evoked CA secretion. It seems that olmesartan has a dual action, acting as both agonist and antagonist at nicotinic receptors of the isolated perfused rat adrenal medulla, which might be dependent on the concentration. It is also thought that this inhibitory effect of olmesartan may be mediated by blocking the influx of both $Na^+$ and $Ca^{2+}$ into the rat adrenomedullary chromaffin cells as well as by inhibiting the $Ca^{2+}$ release from the cytoplasmic calcium store, which is thought to be relevant to the $AT_1$ receptor blockade, in addition to its enhancement on the CA secreton.

Characteristics and Geoeffectiveness of Small-scale Magnetic Flux Ropes in the Solar Wind

  • Kim, Myeong Joon;Park, Kyung Sun;Lee, Dae-Young;Choi, Cheong-Rim;Kim, Rok Soon;Cho, Kyungsuk;Choi, Kyu-Cheol;Kim, Jaehun
    • Journal of Astronomy and Space Sciences
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    • v.34 no.4
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    • pp.237-244
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    • 2017
  • Magnetic flux ropes, often observed during intervals of interplanetary coronal mass ejections, have long been recognized to be critical in space weather. In this work, we focus on magnetic flux rope structure but on a much smaller scale, and not necessarily related to interplanetary coronal mass ejections. Using near-Earth solar wind advanced composition explorer (ACE) observations from 1998 to 2016, we identified a total of 309 small-scale magnetic flux ropes (SMFRs). We compared the characteristics of identified SMFR events with those of normal magnetic cloud (MC) events available from the existing literature. First, most of the MCs and SMFRs have similar values of accompanying solar wind speed and proton densities. However, the average magnetic field intensity of SMFRs is weaker (~7.4 nT) than that of MCs (~10.6 nT). Also, the average duration time and expansion speed of SMFRs are ~2.5 hr and 2.6 km/s, respectively, both of which are smaller by a factor of ~10 than those of MCs. In addition, we examined the geoeffectiveness of SMFR events by checking their correlation with magnetic storms and substorms. Based on the criteria Sym-H < -50 nT (for identification of storm occurrence) and AL < -200 nT (for identification of substorm occurrence), we found that for 88 SMFR events (corresponding to 28.5 % of the total SMFR events), substorms occurred after the impact of SMFRs, implying a possible triggering of substorms by SMFRs. In contrast, we found only two SMFRs that triggered storms. We emphasize that, based on a much larger database than used in previous studies, all these previously known features are now firmly confirmed by the current work. Accordingly, the results emphasize the significance of SMFRs from the viewpoint of possible triggering of substorms.

Expression of peroxisome proliferator activated receptor gamma in the neuronal cells and modulation of their differentiation by PPAR gamma agonists

  • Hong, Jin-Tae
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2002.11b
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    • pp.14-40
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    • 2002
  • 15-Deoxy- Δ$\^$12,14/-prostaglandin J$_2$ (15-deoxy-PGJ$_2$), a naturally occurring ligand activates the peroxisome proliferator-activated receptor-${\gamma}$ (PPAR-${\gamma}$). Activation of PPAR-y has been found to induce cell differentiation such as adipose cell and macrophage. Here it was investigated whether 15-deoxy-PGJ$_2$ has neuronal cell differentiation and possible underlying molecular mechanisms. Dopaminergic differentiating PC 12 cells treated with 15-deoxy-PGJ$_2$ (0.2 to 1.6 ${\mu}$M) alone showed measurable neurite extension and expression of neurofilament, markers of cell differentiation. However much greater extent of neurite extension and expression of neurofilament was observed in the presence of NGF (50 ng/$m\ell$). In parallel with its increasing effect on the neurite extension and expression of neurofilament, 15-deoxy-PGJ$_2$ enhanced NGF-induced p38 MAP kinase expression and its phosphorylation in addition to the activation of transcription factor AP-1 in a dose dependent manner. Moreover, pretreatment of SD 203580, a specific inhibitor of p38 MAP kinase inhibited the promoting effect of 15-deoxy-PGJ$_2$ (0.8 ${\mu}$M) on NGF-induced neurite extension. This inhibition correlated well with the ability of SB203580 to inhibit the enhancing effect of 15-deoxy-PGJ$_2$ on the expression of p38 MAP kinase and activation of AP-1. The promoting ability of 15-deoxy-PGJ$_2$ did not occur through PPAR-${\gamma}$, as synthetic PPAR-${\gamma}$ agonist and antagonist did not change the neurite promoting effect of 15-deoxy-PGJ$_2$. In addition, contrast to other cells (embryonic midbrain and SK-N-MC cells), PPAR-${\gamma}$ was not expressed in PC-12 cells. Other structure related prostaglandins, PGD$_2$ and PGE$_2$ acting via a cell surface G-protein-coupled receptor (GPCR) did not increase basal or NGF-induced neurite extension. Moreover, GPCR (EP and DP receptor) antagonists did not alter the promoting effect of 15-deoxy-PGJ$_2$ on neurite extension and activation of p38 MAP kinase, suggesting that the promoting effect of 15-deoxy-PGJ$_2$ may not be mediated GPCR. These data demonstrate that activation of p38 MAP kinase in conjunction with AP-1 signal pathway may be important in the promoting activity of 15-deoxy-PGJ$_2$ on the differentiation of PC12 cells.

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Sodium butyrate reduces high-fat diet-induced non-alcoholic steatohepatitis through upregulation of hepatic GLP-1R expression

  • Zhou, Da;Chen, Yuan-Wen;Zhao, Ze-Hua;Yang, Rui-Xu;Xin, Feng-Zhi;Liu, Xiao-Lin;Pan, Qin;Zhou, Huiping;Fan, Jian-Gao
    • Experimental and Molecular Medicine
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    • v.50 no.12
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    • pp.2.1-2.12
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    • 2018
  • Glucagon-like peptide-1 (GLP-1) has a broad spectrum of biological activity by regulating metabolic processes via both the direct activation of the class B family of G protein-coupled receptors and indirect nonreceptor-mediated pathways. GLP-1 receptor (GLP-1R) agonists have significant therapeutic effects on non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) in animal models. However, clinical studies indicated that GLP-1 treatment had little effect on hepatic steatosis in some NAFLD patients, suggesting that GLP-1 resistance may occur in these patients. It is well-known that the gut metabolite sodium butyrate (NaB) could promote GLP-1 secretion from intestinal L cells. However, it is unclear whether NaB improves hepatic GLP-1 responsiveness in NAFLD. In the current study, we showed that the serum GLP-1 levels of NAFLD patients were similar to those of normal controls, but hepatic GLP-1R expression was significantly downregulated in NAFLD patients. Similarly, in the NAFLD mouse model, mice fed with a high-fat diet showed reduced hepatic GLP-1R expression, which was reversed by NaB treatment and accompanied by markedly alleviated liver steatosis. In addition, NaB treatment also upregulated the hepatic p-AMPK/p-ACC and insulin receptor/insulin receptor substrate-1 expression levels. Furthermore, NaB-enhanced GLP-1R expression in HepG2 cells by inhibiting histone deacetylase-2 independent of GPR43/GPR109a. These results indicate that NaB is able to prevent the progression of NAFL to NASH via promoting hepatic GLP-1R expression. NaB is a GLP-1 sensitizer and represents a potential therapeutic adjuvant to prevent NAFL progression to NASH.

A Pilot Study to Evaluate the Reliability of Pattern Identification Tool for Knee Osteoarthritis and to Analyze Correlation between Pattern Identification Tool and Knee Range of Motion, Visual Analog Scale and Western Ontario & Mcmaster Universities Osteoarthritis Index (퇴행성 무릎관절염 변증도구의 신뢰도 평가 및 무릎 ROM, VAS, WOMAC과의 상관관계에 대한 탐색적 연구)

  • Oh, Seung-Joon;Jang, Eunsu;Oh, Young-Seon;Kang, Wee-chang;Lee, Eun-Jung;Jung, In Chul
    • Journal of Korean Medicine Rehabilitation
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    • v.29 no.3
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    • pp.113-128
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    • 2019
  • Objectives To evaluate the pattern identification tool for knee osteoarthritis and to investigate the relationship between pattern identification tool and knee ROM (range of motion), VAS (visual analog scale) and WOMAC (Western Ontario & McMaster Universities osteoarthritis index). Methods We studied 50 patients who are diagnosed as degenerative osteoarthritis. With one patient dropping out, total of 49 patient went through pattern identification tool. Re-test of the pattern identification tool was implemented after about a week. The reliability was analyzed by calculating ICC (intraclass correlation coefficient). Also, reliability of each pattern identification score was calculated along with influence factor and correlation between knee ROM, VAS and WOMAC. Results Reliability of the pattern identification tool was evaluated as 'poor agreement beyond chance' with ICC value of 0.396. Reliablility of each pattern identification score was calculated and four out of five were measured 'good' with one 'moderate' reliability. Two of inter-item consistency were 'good', two were 'acceptable' and one was 'questionable'. Correlation between each pattern identification and knee ROM showed 'clear negative linear relationship' with two patterns. VAS showed 'clear positivie linear relationship' with all five patterns. WOMAC showed 'positivie linear relationship' with all five patterns. Conclusions According to the results, pattern identification tool for knee osteoarthritis seems to have meaningful relationship with other agnedas. Also, further research is needed to develop the tool.

A Comparative Study of a Deeply-inserted Acupotomy Applied to Hyeopcheok Points and Usual Korean Medicine Treatments for Lumbosacral Radiculopathy: Safety, Effectiveness, Cost-effectiveness: A Study Protocol (요천추신경병증에 대한 심부협척 도침술과 한의통상치료의 효과 비교: 안전성, 유효성, 경제성평가: 연구 프로토콜)

  • Heo, In;Lee, Jin-Hyun;Ko, Youn-Suk;Jo, Dong Chan;Kim, Young Il;Lee, Sang-Hyun;Hwang, Eui-Hyoung;Park, Tae-Yong;Hwang, Man-Suk
    • The Journal of Churna Manual Medicine for Spine and Nerves
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    • v.16 no.2
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    • pp.69-77
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    • 2021
  • 연구 배경 최근 한국 및 중국에서 근골격계 질환에 대한 도침술의 활용이 늘고 있다. 하지만 현재까지의 임상연구는 대부분 증례보고 형태에 그치거나, 충분한 근거가 확보되지는 않은 실정이다. 우리는 요천추신경병증환자의 치료에 있어 도침치료와 통상한의치료와의 비교를 통해 도침치료의 유효성, 안전성, 경제성 평가를 시행하기 위해 본 연구를 기획하게 되었다. 연구 방법 본 연구는 예비임상 연구로, 다기관에서 진행되며, 무작위대조군, 활성 대조군을 통한 2개군 병행집단 연구로 평가자 맹검을 시행하게 된다. 이 연구에서는 총 50명의 요천추신경병증 환자를 대상으로 2개군으로 균등하게 분배하여 도침술 또는 통상한의치료를 시행하게 된다(각군당 25명). 도침술 그룹의 경우 협척혈에 도침치료를 시행 받게 되며, 통상 한의치료군은 연구자 판단하에 도침술을 제외한 적절한 한의치료를 시행 받게 된다. 두 개의 그룹은 주당 2회씩 총 3주간 치료를 받게 된다. 일차 유효성 평가는 요통으로 인한 기능장애를 평가하기 위한 Oswestry disability index를 통해 시행한다. 이차 유효성 평가지표로는 numeric rating scale, European Quality of Life 5-Dimension 5-Level, short-form McGill Pain Questionnaire, Roland-Morris Disability Questionnaire scores를 시행하게 된다. 고찰 본 예비임상연구의 결과는 추후 있을 요천추신경병증에 대한 도침치료 및 한의통상치료 비교효과 연구의 유효성, 경제성평가 본 임상연구를 위한 기초 정보 및 가능성을 확인하고 적절한 대상자수 산정에 도움이 될 것이다.

Analysis of activated colloidal crud in advanced and modular reactor under pump coastdown with kinetic corrosion

  • Khurram Mehboob;Yahya A. Al-Zahrani
    • Nuclear Engineering and Technology
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    • v.54 no.12
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    • pp.4571-4584
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    • 2022
  • The analysis of rapid flow transients in Reactor Coolant Pumps (RCP) is essential for a reactor safety study. An accurate and precise analysis of the RCP coastdown is necessary for the reactor design. The coastdown of RCP affects the coolant temperature and the colloidal crud in the primary coolant. A realistic and kinetic model has been used to investigate the behavior of activated colloidal crud in the primary coolant and steam generator that solves the pump speed analytically. The analytic solution of the non-dimensional flow rate has been determined by the energy ratio β. The kinetic energy of the coolant fluid and the kinetic energy stored in the rotating parts of a pump are two essential parameters in the form of β. Under normal operation, the pump's speed and moment of inertia are constant. However, in a coastdown situation, kinetic damping in the interval has been implemented. A dynamic model ACCP-SMART has been developed for System Integrated Modular and Advanced Reactor (SMART) to investigate the corrosion due to activated colloidal crud. The Fickian diffusion model has been implemented as the reference corrosion model for the constituent component of the primary loop of the SMART reactor. The activated colloidal crud activity in the primary coolant and steam generator of the SMART reactor has been studied for different equilibrium corrosion rates, linear increase in corrosion rate, and dynamic RCP coastdown situation energy ratio b. The coolant specific activity of SMART reactor equilibrium corrosion (4.0 mg s-1) has been found 9.63×10-3 µCi cm-3, 3.53×10-3 µC cm-3, 2.39×10-2 µC cm-3, 8.10×10-3 µC cm-3, 6.77× 10-3 µC cm-3, 4.95×10-4 µC cm-3, 1.19×10-3 µC cm-3, and 7.87×10-4 µC cm-3 for 24Na, 54Mn, 56Mn, 59Fe, 58Co, 60Co, 99Mo, and 51Cr which are 14.95%, 5.48%, 37.08%, 12.57%, 10.51%, 0.77%, 18.50%, and 0.12% respectively. For linear and exponential coastdown with a constant corrosion rate, the total coolant and steam generator activity approaches a higher saturation value than the normal values. The coolant and steam generator activity changes considerably with kinetic corrosion rate, equilibrium corrosion, growth of corrosion rate (ΔC/Δt), and RCP coastdown situations. The effect of the RCP coastdown on the specific activity of the steam generators is smeared by linearly rising corrosion rates, equilibrium corrosion, and rapid coasting down of the RCP. However, the time taken to reach the saturation activity is also influenced by the slope of corrosion rate, coastdown situation, equilibrium corrosion rate, and energy ratio β.

Development of community-based intensive health care program for the community dwelling elderly (재가노인을 위한 지역사회 중심의 집중건강관리프로그램의 개발과 적용)

  • Song, Mi-Sook;Song, Hyun Jong
    • 한국노년학
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    • v.29 no.1
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    • pp.37-50
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    • 2009
  • The purpose of the present study was to develop a community-based intensive health care program for the community dwelling elderly to strength their functional status and to verify the effect on their geriatric syndrome. A one-group pretest-posttest design was used for the study. A total of 69 frail elderly, who lived in the area within 20 minutes by car, were committed themselves to the day care center(Sangikjae), and had the ability of verbal communication were selected from G city in Kyunggi province. The participants completed a set of questionnaires to measure the sub-score of frailty, fall, urinary incontinence, malnutrition, and mild cognitive disorder domain, using the Otasha-Kensin through the physical examinations and interviews. After 4 weeks of intervention, the outcome was measured to evaluate the effects of the program, and the data obtained were analyzed using descriptive statistics, paired t-test and McNemar test. The results showed that the sub-score of frailty, fall, urinary incontinence, and malnutrition domain were statistically significantly decreased after intervention except those of urinary incontinence and mild cognitive disorder domain, implying that the risk of frailty, fall, and malnutrition was decreased. These findings indicated that community-based the intensive health care program is effective for relieving geriatric syndrome of the community dwelling elderly.

Sex Differentiation of the Gonad in Red Sea Bream, Pagrus major with Cultured Condition (양식산, 참돔 Pagrus major의 생식소 성분화)

  • 김형배
    • Journal of Aquaculture
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    • v.11 no.4
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    • pp.529-546
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    • 1998
  • Gonadal part that developed by indifferentiation period for 6 months after hatching is made as gonad and fat body. These gonad are thin semi-transparant and undistinguished germ cell. Germinal epithelium is distinguished by development of gonad epithelial tissue from 7 months after hatching. Sex differentiation is begun by oogonia develoment at 8 months after hatching. Primary oocytes grow over germinal epithelium of gonadal cavity, at 9 months after hatching, gonadal cavity become ovarian cavity as they increasing. As soon as oocytes at 13 months after hatching are filled with the whole part of gonad, degeneration of oocyte is begun. And then, gonad has cavity tissue, a small number of oocyte are located in gonadal cavity. At 15 months after hatching, new primary oocyte develop and cavity of ovarian tissue in the central of ovarian cavity. Spermatogonia multiplicate and cavity tissue consist of testicular tissue. These gonad become hermaphrodite and then ditermine the sex of female and male. These results show the red sea bream is juvenile hermaphrodite and undif-ferentiated gonochoristic teleost. Male and female differentiation type of gonad is divided in undifferentiation stage, oogonia-like stage, ovary-like stage, ovary development stage, hermaphroditic testis stage, hermaphroditic ovary stage, and testis development stage. Undifferentiation stage is continued total lenth 18cm at 13 months after hatching. ovary-like stage is continued total length 11~18cm at 13 months after hatching. Ovary-like stage is continued total length 14~26cm at 10~14 months after hatching. Ovary development stage begins from total length 20cm, 14 months after hatching. At 20 months after hatching, 44 percent of total sampled individuals had ovary. Hermaphroditic ovary stage first begins total length 19~20 cm at 15 months after hatching, but it is not observed total length 28~29cm at 20months after hatching. Hermaphroditic testis stage first begins total length 21~22cm at 20months after hatching and is continued for 20months. Testis development stage first begins total length 20~21cm at 20 months after hatching, and is occupied 33 percent total length 28~29cm at 20 months. The beginning of sex differentiation more than 50 percent is from total length 16cm at 11 months after hatching. Sex determination begins total length 20cm, 14months after hatching in female and total length 20cm, 15 months after hatching in male. Sex determination more than 50 percent begins total length 23cm,, 17 months after hatching. Undifferentiated gonadal part of red sea bream consist gonad and fat body. As differentiation is going on and gonad is growing, fat body shrinks. This appearence is showed the same tendency in 3-year old red sea bream. 1.9mm larvae after hatching grow about 19mm larvae for 47 days. The relationship between the total length and body weight of larvae and juveniles in $BW=4.45{\times}10^{-6}TL^{3.4718}$ r=0.9820. Fishes in cage culture grow to maximum total length 28.4cm. The relationship between the total length and body weight of these fishes is $BW=2.36{\times}10^{-2}TL^{2.9180}$, r=0.9971. Undifferentiated gonadal part of red sea bream consist gonad and fat body. As differentiation is going on and gonad is growing, fat body shrinks.

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Effect of Solvent Fractions from Methanol Extract of Doenjang on Inhibition of Growth and DNA Synthesis of Human Cancer Cells. (인체 암세포 성장 및 DNA 합성 억제에 미치는 된장 분획물의 영향)

  • LIM Sun-Young;Rhee Sook-Hee;Park Kun-Young
    • Journal of Life Science
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    • v.15 no.5 s.72
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    • pp.685-691
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    • 2005
  • Growth and DNA synthesis inhibitory effects of doenjang methanol extract and its solvent fractions on AGS human gastric adenocarcinoma cells, Hep 3B human hepatocellular carcinoma cells, HT-29 human colon cancer cells and MG-63 human osteosarcoma cells were studied. The treatment of doenjang methanol extract ($ 200{\mu}g/ml $) with the AGS, Hep 3B, HT-29 and MG-63 cancer cells after 6 days of incubation inhibited the growth of cancer cells by $32\%$, $51\%$, $84\%$ and $33\%$, respectively. To separate active compounds of doenjang, doenjang methanol extract was fractionated with dichloromethane, ethylacetate, and buthanol. Among the solvent fractions, the dichloromethane and ethylacetate fractions showed the highest growth inhibitory effects on various cancer cells. For example, the dichloromethane and ethylacetate fractions ($200a{\mu}g/ml$) sig-nificantly inhibited the growth of various cancer cells by $89\∼96\%$ and$62\∼86\%$, respectively. DNA synthesis of AGS and Hep 3B cancer cells was significantly inhibited by adding dichloromethane fraction ($200{\mu}g/ml$) up to $94\%$ and $80\%$, respectively. Similarly, the ethylacetate fraction ($ 200\mug/ml $) showed a $ 95\% $ inhibition rate of DNA synthesis in AGS cells. These results suggest that the dichloromethane and ethylacetate fractions have specific active compounds, which will explain this anticancer effect of doenjang.