• Title/Summary/Keyword: dose response

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Effect of ATP on Calcium Channel Modulation in Rat Adrenal Chromaffin Cells (흰쥐 부신 크로마핀 세포 칼슘통로 조절에 미치는 ATP의 효과)

  • Kim, Kyung Ah;Goo, Yong Sook
    • Progress in Medical Physics
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    • v.25 no.3
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    • pp.157-166
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    • 2014
  • ATP in quantity co-stored with neurotransmitters in the secretory vesicles of neurons, by being co-released with the neurotransmitters, takes an important role to modulate the stimulus-secretion response of neurotransmitters. Here, in this study, the modulatory effect of ATP was studied in $Ca^{2+}$ channels of cultured rat adrenal chromaffin cells to investigate the physiological role of ATP in neurons. The $Ca^{2+}$ channel current was recorded in a whole-cell patch clamp configuration, which was modulated by ATP. In 10 mM $Ba^{2+}$ bath solution, ATP treatment (0.1 mM) decreased the $Ba^{2+}$ current by an average of $36{\pm}6%$ (n=8), showing a dose-dependency within the range of $10^{-4}{\sim}10^{-1}mM$. The current was recovered by ATP washout, demonstrating its reversible pattern. This current blockade effect of ATP was disinhibited by a large prepulse up to +80 mV, since the $Ba^{2+}$ current increment was larger when treated with ATP ($37{\pm}5%$, n=11) compared to the control ($25{\pm}3%$, n=12, without ATP). The $Ba^{2+}$ current was recorded with $GTP{\gamma}S$, the non-hydrolyzable GTP analogue, to determine if the blocking effect of ATP was mediated by G-protein. The $Ba^{2+}$ current decreased down to 45% of control with $GTP{\gamma}S$. With a large prepulse (+80 mV), the current increment was $34{\pm}4%$ (n=19), which $25{\pm}3%$ (n=12) under control condition (without $GTP{\gamma}S$). The $Ba^{2+}$ current waveform was well fitted to a single-exponential curve for the control, while a double-exponential curve best fitted the current signal with ATP or $GTP{\gamma}S$. In other words, a slow activation component appeared with ATP or $GTP{\gamma}S$, which suggested that both ATP and $GTP{\gamma}S$ caused slower activation of $Ca^{2+}$ channels via the same mechanism. The results suggest that ATP may block the $Ca^{2+}$ channels by G-protein and this $Ca^{2+}$ channel blocking effect of ATP is important in autocrine (or paracrine) inhibition of adrenaline secretion in chromaffin cell.

Oxidized LDL is a Chemoattractant for the Eosinophils and Neutrophils (산화 저비중 리포 단백이 호산구와 호중구에 대한 화학주성)

  • Hwang, Young-Sil;Lee, Jong-Deog;Busse, William B.
    • Tuberculosis and Respiratory Diseases
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    • v.51 no.3
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    • pp.211-223
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    • 2001
  • Background : Rhinovirus infection of the airways results in increased permeability of the airway vascular endothelium with the influx of plasma proteins, including lipids such as LDL. In vitro studies on the effect of oxLDL on leukocytes has shown many pro inflammatory effects on multiple leukocytes. We hypothesized that oxLDL is one mechanism for recruiting granulocytes to the airways during a RV infection. Therefore, chemotaxis and transendothelial migration, in response to nLDL, was determined for these granulocytes. Methods : nLDL was oxidized with 5mM Cu2S04 for 20-24 hours. 3-5 105 cells were loaded into the Transwell filter while the chemotatic agonists were placed in the lower well for chemotaxis. Confluent monolayers on HPMEC were grown on Transwell filters for transendothelial migration. The filters were washed and eosinophils and neutrophils loaded on to the filter with the chemotatic agonist was were placed in the lower well. The wells were incubated for 3 hours. The number of migrating cells was counted on a hemocytometer. Results : OxLDL, but not nLDL, is chemotatic for eosinophils and neutrophils. The level of granulocytes chemotaxis was dependent on both the concentration of LDL and its degree of oxidation. OxLDL stimulates eosinophil and neutrophils migration across HPMEC monolayers (+/-IL-$1{\beta}$ preactivation) in a dose dependent manner. Conclusion : Increased vascular permeability during a RV infection may lead to the influx and oxidation of LDL. The resulting oxLDL. is one possible mechanism for the recruitment of neutrophils and eosinophils to the airway interstitial matrix. Once in the airways, granulocytes can further interact with oxLDL to promote airway inflammation.

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Enhancement of Tumor Response by MEK Inhibitor in Murine HCa-I Tumors (C3H/HeJ 마우스 간암에서 MEK 억제제에 의한 방사선 감수성 향상 효과)

  • Kim, Sung-Hee;Seong, Jin-Sil
    • Radiation Oncology Journal
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    • v.21 no.3
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    • pp.207-215
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    • 2003
  • Purpose: Extracellular signal-regulated kinase (ERK), which is part of the mitogen-activated protin kinase cascade, opposes initiation of the apoptotic cell death which is programmed by diverse cytotoxic stimuli. In this regard, the inhibition of ERK may be useful in improving the therapeutic efficacy of established anticancer agents. Materials and Methods: Murine hepatocarcinoma, HCa-I is known to be highly radioresistant with a TCD50 (radiation dose yield in $50\%$ cure) of more than 80 Gy. Various anticancer drugs have been found to enhance the radioresponse of this particular tumor but none were successful. The objective of this study was to explore whether the selective inhibition of MEK could potentiate the antitumor efficacy of radiation in vivo, particularly in the case on radioresistant tumor. C3H/HeJ mice hearing $7.5\~8\;mm$ HCa-I, were treated with PD98059(intratumoral injection of $0.16\;\mug/50\;\mul$). Results: Downregulation on ERK by PD98059 was most prominent 1h after the treatment. In the tumor growth delay assay, the drug was found to Increase the effect of the tumor radioresponse with an enhancement factor (EF) of 1.6 and 1.87. Combined treatment of 25 Gy radiation with PD98059 significantly increased radiation induced apoptosis. The peak apoptotic index (number on apoptotic nuclei in 1000 nuclei X100) was $1.2\%$ in the case of radiation treatment alone, $0.9\%$ in the case of drug treatment alone and $4.9\%,\;5.3\%$ in the combination treatment group. An analysis of apoptosis regulating molecules with Western blotting showed upregulation of p53, p$p21^{WAF1/CIP1}\;and\;Bcl-X_s$ in the combination treatment group as compared to their levels in either the radiation alone or drug alone treatment groups. The level of other molecules such as $Bcl-X_L4, Bax and Bcl-2 were changed to a lesser extent. Conclusion: The selective inhibition of MEK in combination with radiation therapy may have potential benefit in cancer treatment.

Analysis of Nutritional Composition and Effects of Yak-sun Tea Prescription from Oriental Medicinal Herbs for Serum Lipid Levels and Homocystein Content (한약자원을 이용한 약선차의 영양성분 분석 및 약선차의 섭취가 여대생의 혈청지질수준과 호모시스테인 농도에 미치는 효과)

  • Han, Jong-Hyun;Song, You-Jin;Park, Sung-Jin;Park, Sung-Hye
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.35 no.5
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    • pp.557-564
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    • 2006
  • This research was planned and executed to evaluate how the composition of Yak-sun (oriental diet therapy) can effect health conditions of people who are suffering from diet-related diseases like obesity and hyper lipidemia by taking Yak-sun in a form of nutritional supplement with our daily meals. We produced Yak-sun tea with $Ky\hat{a}lmy\hat{a}ngja$, Kamguk, $K\hat{u}m\hat{u}nhwa$, Ch'onkung and observed nutritional composition and evaluated how this tea effects on serum lipids and homocystein concentration by clinical practices. With this observation, we found out that this tea has significant effect on increasing of HDL-cholesterol, decreasing of LDL-cholesterol and homocysteine concentration, and we think that scientific and objective evaluation was done on the components of Yak-sun tea prescription. We concluded that we could apply the components not only in a form of tea, but also in other forms of various food. The information we received from this conclusion will be a basic information on how we can apply oriental medicinal resources into other food and will also be a stepping stone for medicinal herbs to step foot in the field of functional food research, which already draws sizable attention world-wide.

Quantitative Microbial Risk Assessment Model for Staphylococcus aureus in Kimbab (김밥에서의 Staphylococcus aureus에 대한 정량적 미생물위해평가 모델 개발)

  • Bahk, Gyung-Jin;Oh, Deog-Hwan;Ha, Sang-Do;Park, Ki-Hwan;Joung, Myung-Sub;Chun, Suk-Jo;Park, Jong-Seok;Woo, Gun-Jo;Hong, Chong-Hae
    • Korean Journal of Food Science and Technology
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    • v.37 no.3
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    • pp.484-491
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    • 2005
  • Quantitative microbial risk assessment (QMRA) analyzes potential hazard of microorganisms on public health and offers structured approach to assess risks associated with microorganisms in foods. This paper addresses specific risk management questions associated with Staphylococcus aureus in kimbab and improvement and dissemination of QMRA methodology, QMRA model was developed by constructing four nodes from retail to table pathway. Predictive microbial growth model and survey data were combined with probabilistic modeling to simulate levels of S. aureus in kimbab at time of consumption, Due to lack of dose-response models, final level of S. aureus in kimbeb was used as proxy for potential hazard level, based on which possibility of contamination over this level and consumption level of S. aureus through kimbab were estimated as 30.7% and 3.67 log cfu/g, respectively. Regression sensitivity results showed time-temperature during storage at selling was the most significant factor. These results suggested temperature control under $10^{\circ}C$ was critical control point for kimbab production to prevent growth of S. aureus and showed QMRA was useful for evaluation of factors influencing potential risk and could be applied directly to risk management.

Effects of 3,5-di-O-Caffeoylquinic acid from Artemisia scoparia Waldstein et Kitamura on the Function of HPV 16 Oncoproteins (인진에서 분리한 3,5-di-O-Caffeoylquinic acid가 자궁경부암 바이러스 발암단백질의 기능에 미치는 영향)

  • Baek, Tae-Woong;Lee, Kyung-Ae;Ahn, Min-Jung;Joo, Hae-Kyung;Cho, Min-Chul;Kang, Jung-Woo;Kim, Hee-Seo;Shim, Jung-Hyun;Lee, Hee-Gu;Oh, Hyun-Cheol;Ahn, Jong-Seok;Cho, Yong-Kwen;Myung, Pyung-Keun;Yoon, Do-Young
    • Korean Journal of Pharmacognosy
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    • v.35 no.4 s.139
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    • pp.368-374
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    • 2004
  • Cervical cancer is one of the leading causes of female death. Viral oncoproteins E6 and E7 are selectively retained and expressed in carcinoma cells infected with HPV (Human papillomavirus) type 16. The HPV is cooperated in immotalization and transformation of primary keratinocyte. E6 and E7 oncoproteins interfere the functions of tumor suppressor proteins p53 and retinoblasoma protein (pRb), respectively. Among a lots of natural products, Artemisia scoparia Waldstein et Kitamura has inhibitory effects on the binding between E6 oncoprotein and tumor suppressor p53, or the binding between E6 and E6 associated protein (E6AP), an E3 ubiquitin-protein ligase. HPV oncoprotein inhibitors from Artemisia scoparia W. were isolated by solvent partition and column chromatography (Silica gel, RP-18) and the inhibitory compounds were finally purified by HPLC using an ELISA screening system based on the binding between E6 and E6AP. The aim of this study is to identify the structure of inhibitory compounds and to investigate whether these compounds have inhibitory effects on the functions of E6 oncoprotein. We investigated whether 3,5-di-O-caffeoylquinic acid (DCQA) extracted from Artemisia scoparia W. Could inhibit the function of E6 oncoprutein. DCQA inhibited the in vitro binding of E6 and E6AP which are essential for the binding and degradation of the tumor suppressor p53 and also inhibited the proliferation of human cervical cancer cell lines (SiHa and CaSKi) in a dose response manner. These results suggest that DCQA inhibited the function of E6 oncoprotein, suggesting that it can be used as a potential drug for the treatment of cervical cancers infected with HPV.

Health Assessment for Glass Fibre Landfill at Gozan-dong, Inchon (인천시 고잔동에서 제기된 유리섬유에 의한 건강피해 역학 조사)

  • Cho, Soo-Hun;Ju, Yeong-Su;Kim, Kyung-Ryul;Lee, Kang-Kun;Hong, Kug-Sun;Eun, Hee-Chul;Song, Dong-Bin;Hong, Jae-Woong;Kwon, Ho-Jang;Ha, Mi-Na;Han, Sang-Hwan;Seong, Joo-Heon;Kang, Jong-Won
    • Journal of Preventive Medicine and Public Health
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    • v.30 no.1 s.56
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    • pp.77-101
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    • 1997
  • In September 1994, residents of Gozan-dong, Incheon City, made a petition to the government about their health problems which might be caused by previous glass fibre landfill nearby 'H' company. In february 1995, at regular academic meeting of occupational and environmental medicine, a research team of 'D' University presented that they had found glass fibres in groundwater of the area through their survey. They were suspicious of probable association between ingestion of groundwater contaminated with glass fibres and skin tumors among residents. A joint research team was formed and carried out the survey of environment concerning groundwater and its glass fibre existence, and health assessment of residents in the area and industrial workers of 'H' company during May to November, 1995. Analysis of groundwater flow system indicates that the flow lines from the glass fibre landfill pass through or terminate at the 6 houses around the landfill. This means that the groundwater of the 6 houses around the glass fibre landfill could be affected by some possible contaminants from the landfill, but the groundwater quality of the other houses was irrelevant to the landfill. The qualitative and qualitative analyses for glass fibres in 54 groundwater samples including those from the nearby 6 houses, were carried out using SEM equipped with EDS, resulting in no evidence for the presence of glass fibres in the waters. Major precipitates, formed in waters while boiling, were identified as calcium carbonates, in particulary, aragonites in needle form. The results of health assessments of 889 residents in Gozan-dong, participated in this study, showed statistically significant differences in past medical histories of skin tumor and respiratory disease between the exposed group (31 persons who inhabited in 6 houses around the landfill) and the control group, but no significant differences in past medical histories of other diseases, such as cancer mortality, current gastroscopic findings, current skin diseases and respiratory diseases, etc. Also, we could not prove any glass fibres in excised specimens of 9 skin tumors in both groups and there were no health problems possibly associated with glass fibres in employees of the 'H' company. After all, we could not authenticate the association, raised by prior investigators, between groundwater streams, assumedly contaminated with glass fibres or not, and specific disease morbidities or common disease/symptom prevalences. That is, we could not find any glass fibres in groundwater as the only exposure factor of this study hypothesis, and there were not enough certain evidences such as increasing disease prevalences, for examples, skin, respiratory and gastrointestinal diseases etc, possibly related to glass fibre exposure, in exposed group. As a matter of course, the conditions for confirming causal association, for example, strength of the association, consistency of the association, specificity of the association, temporality of the association and dose-response relationship etc, have not been satisfied. In conclusion, we were not able to certify the hypothesis that contamination of groundwater with glass fibres might cause any hazardous health effects in residents who used it for drinking.

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Results of Preoperative Concurrent Chemoradiotherapy for Locally Advanced Rectal Cancer (국소진행성 직장암의 수술 전 동시화학방사선요법의 결과)

  • Choi, Sang-Gyu;Kim, Su-Ssan;Bae, Hoon-Sik
    • Radiation Oncology Journal
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    • v.25 no.1
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    • pp.34-42
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    • 2007
  • [ $\underline{Purpose}$ ]: We performed a retrospective non-randomized clinical study of locally advanced rectal cancer, to evaluate the anal sphincter preservation rates, down staging rates and survival rates of preoperative chemoradiotherapy. $\underline{Materials\;and\;Methods}$: From January 2002 to December 2005, patients with pathologically confirmed rectal cancer with clinical stage T2 or higher, or patients with lymph node metastasis were enrolled in this study. A preoperative staging work-up was conducted in 36 patients. All patients were treated with preoperative chemoradiotherapy, and curative resection was performed for 26 patients at Hallym University Sacred Heart Hospital. Radiotherapy treatment planning was conducted with the use of planning CT for all patients. A total dose of $45.0{\sim}52.2\;Gy$ conventionally fractionated three-dimensional radiotherapy was delivered to the whole pelvis. Chemotherapy was given at the first and fifth week of radiation therapy with continuous infusion i.v. 5-FU (Fluorouracil) and LV (Leucovorine). Surgical resection was performed 2 to 4 weeks after the completion of the chemoradiotherapy regimen. $\underline{Results}$: The complete resection rate with negative resection margin was 100% (26/26). However, a pathologically complete response was not seen after curative resection. Surgery was done by LAR (low anterior resection) in 23 patients and APR (abdomino-perineal resection) in 3 patients. The sphincter preservation rate was 88.5% (23/26), down staging of the tumor occurred in 12 patients (46.2%) and down-sizing of the tumor occurred in 19 patients (73%). Local recurrence after surgical resection developed in 1 patient, and distant metastasis developed in 3 patients. The local recurrence free survival rate, distant metastasis free survival rate, and progression free survival rate were 96.7%, 87% and 83.1%, respectively. Treatment related toxicity was minimal except for one grade 3, one grade 4 anemia, one grade 3 leukopenia, and one grade 3 ileus. $\underline{Conclusion}$: Preoperative concurrent chmoradiotherapy for locally advanced rectal cancer seems to have some potential benefits: high sphincter preservation and down staging. Treatment related toxicity was minimal and a high compliance with treatment was seen in this study. Further long-term follow-up with a larger group of patients is required.

Suppressive Effects of Defatted Green Tea Seed Ethanol Extract on Cancer Cell Proliferation in HepG2 Cells (HepG2 Cell에서 녹차씨박 에탄올 추출물의 암세포 증식 억제효과)

  • Noh, Kyung-Hee;Min, Kwan-Hee;Seo, Bo-Young;Kim, Hye-Ok;Kim, So-Hee;Song, Young-Sun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.40 no.6
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    • pp.767-774
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    • 2011
  • Defatted green tea seed was extracted with 100% ethanol for 4 hr and then fractionated with petroleum ether, ethyl acetate and butanol. The ethanol and butanol extracts showed greater increases in antiproliferation potential against liver cancer cells than petroleum ether, ethyl acetate, $H_2O$, and hot water extracts did. Thus, this study was carried out to investigate the anti-proliferative actions of defatted green tea seed ethanol extract (DGTSE) in HepG2 cancer cells. The DGTSE contained catechins including EGC ($1039.1{\pm}15.2\;g/g$), tannic acid ($683.5{\pm}17.61\;{\mu}g/g$), EC ($62.4{\pm}5.00\;{\mu}g/g$), ECG ($24.4{\pm}7.81\;{\mu}g/g$), EGCG ($20.9{\pm}0.96\;{\mu}g/g$) and gallic acid ($2.4{\pm}0.68\;{\mu}g/g$), but caffeic acid was not detected when analyzed by HPLC. The anti-proliferation effect of DGTSE toward HepG2 cells was 83.13% when treated at $10\;{\mu}g$/mL, of DGTSE, offering an $IC_{50}$ of $6.58\;{\mu}g$/mL. DGTSE decreased CYP1A1 and CYP1A2 protein expressions in a dose-dependent manner. Quinone reductase and antioxidant response element (ARE)-luciferase activities were increased about 2.6 and 1.94-fold at a concentration of $20\;{\mu}g$/mL compared to a control group, respectively. Enhancement of phase II enzyme activity by DGTSE was shown to be mediated via interaction with ARE sequences in genes encoding the phase enzymes. DGTSE significantly (p<0.05) suppressed prostaglandin $E_2$ level, tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) protein expressions, and NF${\kappa}$B translocation, but did not affected nitric oxide production. From the above results, it is concluded that DGTSE may ameliorate tumor and inflammatory reactions through the elevation of phase II enzyme activities and suppression of NF${\kappa}$B translocation and TNF-${\alpha}$ protein expressions, which support the cancer cell anti-proliferative effects of DGTSE in HepG2 cells.

Causative Pathogens and Therapeutic Assessment of Cefprozil in Acute Otitis Media (급성 중이염의 원인 병원균과 Cefprozil 치료의 임상적 평가)

  • Kang, Jin-Han;Kim, Jong Hyun;Park, Yong-Soo;Choi, Young-Chul;Noh, Heil;Yang, Hoon Shik;Kim, Kyu Sung;Moon, Yeon Sook;Hong, Young Jin
    • Clinical and Experimental Pediatrics
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    • v.46 no.5
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    • pp.459-466
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    • 2003
  • Purpose : AOM is the most common bacterial URI in children. The bacteriology and antibiotic Tx of AOM in children has been studied in many countries. But, there is few study of causative pathogens and antibiotic Tx of AOM in our country. In this aspect, we performed prospective clinical study to confirm the causative pathogens and assess the clinical responses of cefprozil in AOM patients. Methods : Thirty three AOM patients enrolled in this study. Tympanocentesis for isolation of causative pathogens were performed before Tx of cefprozil. The study patients received cefprozil with dose of 15 mg/kg/bid.po/day for 10-12 days, and initially assessed the clinical response at 4-5 days after receiving cefprozil and finally at the end visit. In vitro susceptibility tests of cefprozil to isolated pathogens were done by disc diffusion method, and in vitro susceptibility tests of cefaclor and cefixime to isolated pathogens were simultaneously performed. Results : Bacterial pathogens[S. pneumoniae(10), H. influenzae(5), S. aureus(2), M. catarrhalis(1) and Group A stretococcus(1)] were isolated from 19 patients. Clinically, all patients had history of abrupt high fever except one. Tympanic perforation was dominant in pathogens isolated cases, and otalgia was significantly developed in non-pathogens isolated cases. The ages of pathogens isolated cases were usually below 2 years. Eighty four point nine percent of the patients including two cases with isolation of intermediate resistant S. pneumoniae were clinically improved. Antimicrobial in vitro activity to S. pneumoniae of cefprozil were superior than that of cefacor and cefixime. Conclusion : We confirm that bacteria has the causative role in about 60% cases, and S. pneumoniae is the most common pathogen. Clinically, there were some differences in symptoms, signs and ages between pathogens isolated and non-pathogens isolated cases. The clinical responses of cefprozil in our patients revealed similar outcomes to other countries. And we reconfirm that cefprozil may be clinically effective in cases of AOM due to intermediate resistant S. pneumoniae.