• Title/Summary/Keyword: Inhibitors

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Treatment Strategies for Depression during Pregnancy and Lactation (임신과 수유기 우울증의 치료 전략)

  • Lee, Soyoung Irene;Jung, Han-Yong
    • Korean Journal of Biological Psychiatry
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    • v.14 no.2
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    • pp.91-98
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    • 2007
  • Objectives : Considering the impact of depressive illness on physical and mental health of both mother and fetus, specification of a treatment algorithm for depressive disorder during pregnancy is legitimated. This article provides a systemic review of treatments for depressive disorder during pregnancy and lactation. Methods : According to the search strategy of the Clinical Research Center for Depression of Korean Health 21 R & D Project, PubMed and EMBASE were searched using terms with regard to the treatment of depressive disorders during pregnancy and lactation. Reference lists of related reviews and studies were searched. In addition, relevant practice guidelines were searched using the PubMed. All identified clinical literatures were reviewed and summarized in a narrative manner. Results : Pharmacotherapy during pregnancy and lactation requires a comprehensive assessment of the risks and benefits of treatment for both mother and fetus or neonate. Recently, there is growing evidence that the use of tricyclic and selective serotonin reuptake inhibitors during pregnancy and lactation does not result in increased risks of teratogenicity. Treatment strategies are described according to the point of time of pregnancy or lactation. FDA categories for antidepressants during pregnancy and lactation are described. In addition, issues regarding to the electroconvulsive therapy and psychosocial treatment are discussed. Conclusion : The treatment option for depressive disorders during pregnancy and lactation depends on the severity of depressive illnesses of the individual patient. For mild to moderate depression, the non-pharmacological treatment should be considered first. For moderate to severe depression, pharmacotherapy should be administered in addition to the psychosocial treatment. ECT is recommended for depressive disorder of severe intensity. As the research knowledge is limited, the recommendations should based on the best judgement of psychiatrists.

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Investigation of DPPH Radical Scavenging and Pyolyl Endopeptidase Inhibitory Activities of Plant Extracts (천연 식물자원에서 DPPH 라디칼 제거능과 Prolyl Endopeptidase 활성 저해능 탐색)

  • Lee Young Min;Kim Dae Ik;Lee Sung Hyeon;Cho Soo Muk;Chun Hye Kyung;Park Hong Ju;Lee Yeon Sook
    • The Korean Journal of Community Living Science
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    • v.16 no.4
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    • pp.95-102
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    • 2005
  • The present study was performed to investigate the 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging and Proly1 endopeptidase (PEP) inhibitory activities of plant extracts. The whole extract of Fragaria yezoensis inhibited the DPPH radical by $90.4\%$ and the stem of Gingko biloba, Gardenia jasminoides for. grandiflora and Rhododendron yedoensa var. poukhanene, the loaves of Rhododendron mucronulatum var. ciliatum, Gardenia jasminoides for. grandiflora and Corylus sieboldiana var. mandshurice, the fruit of Cornus officinalis, and the root of Gingko biloba showed high DPPH radical scavenging activities. In the case of PEP inhibitory activities, high inhibition was observed in the whole Plant of Fragaria ananassa, Fragaria yezoensis and Hypericum erectum, the stem of Actinidia arguta and Rhododendron yedoensa var. poukhanese, the leaves of Rhododendron yedoensa var. poukhanense and Rosa davurica, the fruit of Cornus officinalis. and the root of Acer okamotoanum. There was significant correlation (P=0.000) between DPPH radical scavenging and prolyl endopeptidase inhibitory activities, thus some of plant extracts such as whole Fragaria yezoensis, fruit of Cornus officinalis had high activities in both DPPH-scavenging and prolyl endopeptidase inhibition. Therefore, it is required to examine the mechanical interaction between DPPH-scavenging and prolyl endopeptidase inhibitory activities and further studying plant extracts with both these activities is desired to develop agents for preventing and treating of Alzheimer's disease.

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NEW ANTIDEPRESSANTS IN CHILD AND ADOLESCENT PSYCHIATRY (소아청소년정신과영역의 새로운 항우울제)

  • Lee, Soo-Jung
    • Journal of the Korean Academy of Child and Adolescent Psychiatry
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    • v.14 no.1
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    • pp.12-25
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    • 2003
  • Objectives:As increasing number of new antidepressants have been being introduced in clinical practice, pharmacological understanding has been broadened. These changes mandate new information and theories to be incorporated into the treatment process of children with depressive disorders. In light of newly coming knowledge, this review intended to recapitulate the characteristics of new antidepressants and to consider the pivotal issues to develope guidelines for the treatment of depression in childhood and adolescence. Methods:Searching the Pub-Med online database for the articles with the key words of 'new', 'antidepressants' and 'children' ninety-seven headings of review articles were obtained. The author selected the articles of pertinent subjects in terms of either treatment guideline or psychopharmacology of new antidepressants. When required, articles about the clinical effectiveness of individual antidepressants were separatedly searched. In addition, the safety information of new antidepressants was acquired by browsing the official sites of the United States Food and Drugs Administration and Department of Health and Human Services. Results:1) For the clinical course, treatment phase, and treatment outcome, the reviews or treatment guidelines adopted the information from adult treatment guidelines. 2) Systematic and critical reviews unambiguously concluded that selective serotonin reuptake inhibitors(SSRIs) excelled tricyclic antidepressants( TCAs) for both efficacy and side effect profiles, and were recommend for the first-line choice for the treatment of children with depressive disorders. 3) New antidepressants generally lacked treatment experiences and randomized controlled clinical trials. 4) SSRIs and other new antidepressants, when used together, might result in pharmacokinetic and/or pharmacodynamic drug-to-drug interaction. 5) The difference of the clinical effectiveness of antidepressants between children and adults should be addressed from developmental aspects, which required further evidence. Conclusion:Treatment guidelines for the pharmacological treatment of childhood and adolescence depression could be constructed on the basis of clinical trial findings and practical experiences. Treatment guidelines are to best serve as the frame of reference for a clinician to make reasonable decisions for a particular therapeutic situation. In order to fulfill this role, guidelines should be updated as soon as new research data become available.

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Apoptotic Cell Death by Pectenotoxin-2 in p53-Deficient Human Hepatocellular Carcinoma Cells (종양억제유전자 p53 결손 인체간암세포에서 Pectenotoxin-2에 의한 Apoptosis 유도)

  • Shin, Dong-Yeok;Kim, Gi-Young;Choi, Byung-Tae;Kang, Ho-Sung;Jung, Jee-H.;Choi, Yung-Hyun
    • Journal of Life Science
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    • v.17 no.10
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    • pp.1447-1451
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    • 2007
  • Through the screening of marine natural compounds that inhibit cancer cell proliferation, we previously reported that pectenotoxin-2 (PTX-2) isolated from marine sponges exhibits selective cytotoxicity against several cell lines in p53-deficient tumor cells compared to those with functional p53. However, the molecular mechanisms of its anti-proliferative action on malignant cell growth are not completely known. To further explore the mechanisms of its anti-cancer activity and to test whether the status of p53 in liver cancer cells correlates with their chemo-sensitivities to PTX-2, we used two well-known hepatocarcinoma cell lines, p53-deficient Hep3B and p53-wild type HepG2. We have demonstrated that PTX-2 markedly inhibits Hep3B cell growth and induces apoptosis whereas HepG2 cells are much more resistant to PTX-2 suggesting that PTX-2 seems to act by p53-independent cytotoxic mechanism. The apoptosis induced by PTX-2 in Hep3B cells was associated with the modulation of DNA fragmentation factor (DFF) family proteins, up-regulation of pro-apoptotic Bcl-2 family members such as Bax and Bcl-xS and activation of caspases (caspase-3, -8 and -9). Blockade of the caspase-3 activity by caspase-3 inhibitor, z-DEVD-fmk, prevented the PTX-2-induced growth inhibition in Hep3B cells. Moreover, treatment with PTX-2 also induced phosphorylation of AKT and extracellular-signal regulating kinase (ERK), but not c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MARK). Specific inhibitors of PI3K inhibitor (LY294002) and ERK1/2 inhibitor (PD98059) significantly blocks PTX-2-induced-anti-proliferative effects, whereas a JNK inhibitor (SP600125) and a p38 MAPK inhibitor (SB203580) have no significant effects demonstrating that the pro-apoptotic effect of PTX-2 mediated through activation of AKT and ERK signal pathway in Hep3B cells.

Extract of Rubus coreanus Fruits Increases Expression and Activity of Endothelial Nitric Oxide Synthase in the Human Umbilical Vein Endothelial Cells (복분자 추출물에 의한 내피세포 NO 합성효소의 활성과 발현 증가)

  • Yoon, Hyun-Joong;Park, Soo-Young;Oh, Sung-Tack;Lee, Kee-Young;Yang, Sung-Yeul
    • Journal of Life Science
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    • v.21 no.1
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    • pp.44-55
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    • 2011
  • This study aimed to investigate the effects of water extract of Rubus coreanus (RCE) on the expression and activity of endothelial nitric oxide synthase (eNOS), as well as its signal transduction pathways in human umbilical vein endothelial cells (HUVECs). The specific inhibitors of NOS show RCE treatment increases NO production in HUVECs due to the up-regulation of eNOS rather than iNOS. The real-time expression level of eNOS mRNA was also increased upon RCE treatment in HUVECs. While a PKC-specific inhibitor, RO-317549, did not alter RCE-induced NO production in HUVECs, tamoxifen (estrogen receptor-specific inhibitor), PD98059 (ERK-specific inhibitor) and LY-294002 (PI3K/Akt-specific inhibitor) did have suppressive effects. Increased NO production by RCE seems to result from a higher level of active eNOS (pSer1177). Specifically, inhibition of ERK not only decreased the level of active eNOS, but also increased the inactive form of the enzyme (pThr495) in HUVECs. This study suggests that RCE treatment increases NO production in HUVECs due to the increased expression and activity of eNOS. It is also shown that RCE-induced eNOS activation occurs partly through the binding of RCE to the estrogen receptor, along with ERK and PI3K/Akt-dependent signal transduction pathways. In addition, the regulatory binding proteins of eNOS including Hsp90 and caveolin-1 were related to these effects of RCE on eNOS activity in HUVECs.

Metalloproteinase Plays a Role in Mucin Secretion (Mucin 분비에 영향을 미치는 Metalloproteinase)

  • Oh, Yeon-Mok;Choi, Hee Jin;Shim, Tae Sun;Lee, Sang Do;Kim, Woo Sung;Kim, Dong-Soon
    • Tuberculosis and Respiratory Diseases
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    • v.56 no.3
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    • pp.289-296
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    • 2004
  • Background : Mucus hypersecretion in the patients with airway diseases represents poor prognosis as well as discomfort. However, there is no known therapy for its effective control. One important component of mucus is mucin, a glycosylated protein, which endows mucus with viscosity. We studied whether a proteinase has a role in mucin secretion and if so, which. Methods : (1) Inhibition of mucin secretion Group-specific proteinase inhibitors were tested to evaluate whether a proteinase belonging to a group of proteinases plays a role in mucin secretion. Phenylmethylsulfonyl fluoride(PMSF, a serine proteinase inhibitor), E-64(a cysteine proteinase inhibitor), Pepstatin(an aspartic proteinase inhibitor) and 1, 10-Phenanthroline(a metalloproteinase inhibitor) were treated into the Calu-3 cell line for 24 hours. The enzyme linked immunoabsorbant assay(ELISA) for MUC5AC was performed to evaluate the amount of mucin secretion and to compare with a control. (2) Stimulation of mucin secretion Matrix metalloproteinase-9(MMP-9), MMP-12 and TACE(TNF-alpha converting enzyme), which are known to be related with airway diseases, were used to be treated into Calu-3 for 24 hours. ELISA for MUC5AC was performed to evaluate the amount of mucin secretion and to compare with the controls. Results : (1) PMSF($10^{-4}M$), E-64($10^{-4}M$), Pepstatin($10^{-6}M$) and 1, 10-Phenanthroline($10^{-4}M$) reduced the MUC5AC secretion by $1{\pm}4.9%$(mean${\pm}$standard deviation; P=1.0 compared with the control), $-6{\pm}3.9%$(P=0.34), $-13{\pm}9.7%$(P=0.34) and $41{\pm}8.2%$(P=0.03), respectively. (2) The amounts of MUC5AC secretion stimulated by MMP-9(250ng/ml), MMP-12(100ng/ml) and TACE(200ng/ml) were $103{\pm}6%$(P=0.39), $102{\pm}8%$(P=1.0) and $107{\pm}13%$(P=0.39), respectively, compared with the controls. Conclusion : Metalloproteinase(s) is (are) suggested to play a role in mucin secretion. It appears that metalloproteinases, other than MMP-9, MMP-12 or TACE, affect the mucin secretion in this in vitro model.

The Physiological Efficacy of Aloe Gel (Aloe Gel의 생리 효과에 대한 고찰 - Gel의 다당류와 미량 성분을 중심으로 -)

  • 서화중
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.24 no.6
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    • pp.1026-1038
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    • 1995
  • Although aloe lost a lot of its previous popularity in modern clinical uses as medicine numerous scientific researches still have claimed the beneficial properties(curing and general tonic effect) of aloe gel. Whereas considerable contradictory reports have helped to confuse the aloe gel issue and continually aroused controversy about aloe gel efficacy. However health food, cosmetic and medicinal products made from aloe gel are widely available in the world market especially in U.S.A. so the growing of Aloe plant and the processing of A. vera gel have become big industries in some countries. In some previous papers the salicylic acid, one of the common trace gel components, was thought to have an analgetic and antinflammatory effect. Large amount of Mg ion in the gel was suggested to act as anesthetic, Mg-lactate as antihistamic, and Aloctin A(a glycoprotein) as wound healer by promoting the cell growth. The carboxypeptidase and bradykinase activity in the gel were proposed to have the pain relieving and antiinflammatory effect. But any of thes etheories concerining the physiological action of the trace gel components has not been demonstrated by modern pharmacology, and failed to be supported by clinical research. It was suggested by some research workers that trace amount of anthraquinone compounds in the gel play an important role to act as false substrate inhibitors for PG and TX production(antiprostanoid effect), by which, they believed, inflammation, burn and frostbite, and infected wound could be healed. This hypothesis has not been substantiated. Butthe suggested antimicrobial action, antidiabetic, and antidotic effect of aloe gel are likely to be attributed to the trace anthraquinone compounds. In a lot of recent experimental reports it has been claimed that aloe gel polysaccharides(acetylglucomannan, acetylmannan, and glycoprotein) have the antimicrobial, antinflammatory, antitumour, and infected wound healing effect by immunoenhancement. It is hoped that these effects will be soon documented in clinical studies, then the controversy on aloe gel beneficial effect will cease. In the 30 days subchronic toxicity test the lowest observed adverse effect level of acemannan(acetylmannan) on dog was 5.0 mg/kg, IP. But the aloe gel is generally agreed to be harmless and non toxic even for the internal use such as health food. In the case of idiosynrasy one must keep the delayed type hypersensitivity reaction of aloe gel in mind. In conclusion it seem to be impossible to simply refuse a lot of evidences made by research workers who have claimed aloe gel's beneficial effects and to deny the fact that there had been long therapeutic histories of Aloe plants.

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Effect of Culture Medium Strength, Plant Growth Regulators and Ethylene Inhibitors for Adventitious Bud Induction from Mature Zygotic Embryo in Larix kaempferi (낙엽송 (Larix kaempferi) 성숙배로부터 부정아 유도를 위한 배지농도, 식물생장조절물질 및 에틸렌 억제제 효과)

  • Kim, Yong Wook
    • Journal of Korean Society of Forest Science
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    • v.103 no.1
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    • pp.72-79
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    • 2014
  • Adventitious buds were produced from the cultures of mature zygotic embryos of Larix kaempferi with the highest frequency in Quoirin & Lepoivre (LP) medium containing 1.0 mg/L zeatin (76.1%). The effective treatments for inducing adventitious shoots growth above 2 mm were shown in Litvay (LM) medium with 0.5 mg/L zeatin (75.2%) or LP medium with 2.0 mg/L zeatin (70.2%), respectively. In experiment with half strength salts medium for induction of the adventitious buds, the effective treatments were obtained from 1/2LP medium with 1.0 (83.3%) or 2.0 mg/L (81.7%) zeatin, respectively. However, the best adventitious shoot growth more than 2 mm appeared in 1/2LM medium with 1.0 mg/L zeatin (66.7%). In experiment with half strength salts medium for induction of the adventitious buds, the effective treatments were obtained from 1/2LP medium with 1.0 (83.3%) or 2.0 mg/L (81.7%) zeatin, respectively. However, the best adventitious shoot growth more than 2 mm appeared in 1/2LM medium with 1.0 mg/L zeatin (66.7%). In experiment of subsequent treatment with various cytokinins for induction of the adventitious buds, the best one (52.9%) was obtained from 1.0 mg/L zeatin for 2weeks, and then subcultured to the medium with 1.0 mg/L thidiazuron (TDZ). The effect of ethylene synergist or inhibitor on adventitious buds induction was examined. The highest rate (34.6%) of adventitious buds marked from the treatments of 1.0 mg/L zeatin+2.0 mg/L MGBG (methylglyoxal bis-[guanylhydrazone]). And the highest no. of adventitious buds(1.5/explant) was shown in the medium with 1.0 mg/L zeatin+2.0 mg/L $CoCl_2$.

Smad6 Gene and Suppression of Radiation-Induced Apoptosis by Genistein in K562 Cells (K562 세포주에서 Genistein에 의해 억제되는 Radiation-induced Apoptosis의 조절 유전자)

  • Jeong, Soo-Jin;Jin, Young-Hee;Yoo, Yeo-Jin;Do, Chang-Ho;Jeong, Min-Ho;Huh, Gi-Yeong;Bae, Hye-Ran;Yang, Kwang-Mo;Moon, Chang-Woo;Oh, Sin-Geun;Hur, Won-Joo;Lee, Hyung-Sik
    • Radiation Oncology Journal
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    • v.19 no.3
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    • pp.245-251
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    • 2001
  • Prupose : The genes involved on the suppression or radiation-induced apoptosis by genistein in K562 leukemia cell line was investigated. Materials and methods : K562 cells in exponential growth phase were irradiated with a linear accelerator at room temperature. For X-ray irradiation and drug treatment, cultures were prepared at $2\times10^5\;cells/mL$. The cells were irradiated with 10 Gy (Clinac 1800C, Varian, USA), Stock solutions of herbimycin A (HMA, Calbiochem, UK) and genistein (Calbiochem, UK) were prepared in dimethylsulfoxide (DMSO, Sigma, UK). After incubation at $37^{\circ}C$ for 24 h, PCR-select cDNA subtractive hybridization, dot hybridization, DNA sequencing and Northern hybridization were examined. Results : Smad6 gene was identified from the differentially expressed genes in K562 cells incubated with genistein which had been selected by PCR-select cDNA subtractive hybridization. The mRNA expression of Smad6 in K562 cells incubated with genistein was also higher than control group by Northern hybridization analysis. Conclusion : We have shown that Smad6 involved on the suppression of radiation-induced apoptosis by genistein in K562 leukemia cell line. It is plausible that the relationship between Smad6 and the suppression of radiation-induced apoptosis is essential for treatment development based on molecular targeting designed to modify radiation-induced apoptosis.

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Susceptibility tests of oral antibiotics including cefixime against Escherichia coli, isolated from pediatric patients with community acquired urinary tract infections (소아 원외 요로감염 환아에서 분리된 E. coli에 대한 cefixime을 포함한 경구 항생제의 감수성 연구)

  • Lee, Soo Young;Lee, Jung Hyun;Kim, Jong Hyun;Hur, Jae Kyun;Kim, Sun Mi;Ma, Sang Hyuk;Kang, Jin Han
    • Clinical and Experimental Pediatrics
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    • v.49 no.7
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    • pp.777-783
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    • 2006
  • Purpose : Urinary tract infection(UTI) is one of the most frequent infections in children. E. coli is the most frequent etiological micropathogen in pediatric community UTI, and E. coli has developed resistance to many antibiotics, highlighting the need for regular surveys of this organism resistant patterns in the community. The aim of this study was to determine the oral antibiotic susceptibility patterns of E. coli, isolated from pediatric patients with uncomplicated community acquired UTI. Methods : E. coli isolates, obtained from pediatric patients with uncomplicated community acquired UTI between October in 2004 to September in 2005. And minimal inhibitory concentrations(MICs) of oral aminopenicillins and beta-lactamase inhibnitors(ampicillin, amoxacillin, ampicillin-sulbactam), oral cephalosporins(cefaclor, cefixime) and sulfa drug(trimethoprime-sulfamethoxazole) were performed according to the National Committee for Clinical Laboratory Standards(NCCLS) guide line. Results : Total 211 organisms were isolated from pediatric out-patients with community UTI. E. coli was the most common organism(89 percent), followed by E. fecalis, Proteus species, S. aureus, M. morganii, and P. aeruginosa. The resistant rates of aminopenicillins and beta-lactamase inhibitors, cefaclor and sulfa drug to E. coli were very high. But, the resistant rate of cefixime was markedly low, and ESBL strains were isolated with small rates. Conclusion : Our study results suggest that aminopenicillins, cefaclor and sulfa drug may not be useful as first line empirical antibiotics to treat pediatric patients with community UTI in Korea. But, 3rd generation cephalosporin such as cefixime can be used as effective second line antibiotics after primary treatment failure, also may be useful as an empirical first line antibiotic. Finally, we conclude that a continuous surveillance study to monitor susceptibility patterns of E. coli in community UTI will be needed for the standard guide lines of empirical oral antibiotic treatment.