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Gefitinib in Selected Patients with Pre-Treated Non-Small-Cell Lung Cancer: Results from a Phase IV, Multicenter, Non-Randomized Study (SELINE)

  • Lee, Kwan-Ho;Lee, Kye-Young;Jeon, Young-June;Jung, Maan-Hong;Son, Choonhee;Lee, Min-Ki;Ryu, Jeong-Seon;Yang, Sei-Hoon;Lee, Jae-Cheol;Kim, Young-Chul;Kim, Sun-Young
    • Tuberculosis and Respiratory Diseases
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    • v.73 no.6
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    • pp.303-311
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    • 2012
  • Background: This study was designed to analyze the efficacy of gefitinib as a second-line therapy, according to the clinical characteristics in Korean patients with non-small-cell lung cancer (NSCLC). Methods: In this Phase IV observational study, we recruited patients, previously failed first-line chemotherapy, who had locally advanced or metastatic NSCLC, and who were found to be either epidermal growth factor receptor (EGFR) mutation-positive or satisfied 2 or more of the 3 characteristics: adenocarcinoma, female, and non-smoker. These patients were administered with gefitinib 250 mg/day, orally. The primary endpoints were to evaluate the objective response rate (ORR) and to determine the relationship of ORRs, depending on each patient's characteristics of modified intent-to-treat population. Results: A total of 138 patients participated in this study. One subject achieved complete response, and 42 subjects achieved partial response (ORR, 31.2%). The subgroup analysis demonstrated that the ORR was significantly higher in patients with EGFR mutation-positive, compared to that of EGFR mutation-negative (45.8% vs. 14.0%, p=0.0004). In a secondary efficacy variable, the median progression-free survival (PFS) was 5.7 months (95% confidence interval, 3.9~8.4 months) and the 6-month PFS and overall survival were 49.6% and 87.9%, respectively. The most common reported adverse events were rash (34.4%), diarrhea (26.6%), pruritus (17.5%), and cough (15.6%). Conclusion: Gefitinib was observed in anti-tumor activity with favorable tolerability profile as a second-line therapy in these selected patients. When looking at EGFR mutation status, EGFR mutation-positive showed strong association with gefitinib by greater response and prolonged PFS, compared with that of EGFR mutation-negative.

A Study on Community Nutritional Survey for the improvement of National Nutritional Survey - Knowledge, Knowledge Practice, Attitude, Food Practice - (국민영양조사 개선을 위한 지역사회 영양조사연구 - 지식, 실기, 태도, 식행동을 중심으로 -)

  • Kang, Ji-Yong;Wie, Cha-Hyung;Ha, Eun-Hee;Kwak, Jung-Ok;Kim, In-Sook
    • Journal of agricultural medicine and community health
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    • v.22 no.2
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    • pp.147-158
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    • 1997
  • The purpose of this study is to develop the nutritional survey indices such as the Knowledge(K), Knowledge Practice(KP), Attitude(A), and Food Practice(FP) as effective materials of the nutrition education and evaluation in spreading community nutrition service. These materials were applied to two groups(126 rural people and 117 urban people) from August 1st to September 10th, 1996. We investigated actual conditions of objects about K, KP, A, FP by interviews. Also we measured serum cholesterol levels of all objects by Accutelend G.C. The results of the research turned out as follows; 1). In the comparison of the nutritional Knowledge scores, the average score of urban people was much higher($84.2{\pm}2.4$) than rural people($42.1{\pm}3.1$). 2). In the scores of the Knowledge Practice, urban people had also significantly higher score than rural people. But only 19.5% of urban people had high scores between 80 and 100, and 42.4% of urban people and 87.3% of rural people had scores between 0 and 40. 3). The average scores of the Attitude were not significantly different between urban and rural people. The average scores of the Food Practice were not significantly different between urban and rural people. 4). In cholesterol measurements, only three of 243 people were in the abnormal high levels(more than 250mg/dl), and they are all over 60 years old, and two of them were rural people. 5). The people who were younger in age, higher in educational level and spent more money for foods had higher scores on K, KP, A and FP. And the people who were younger in age in age and more money spent for foods had higher scores on FP. Regression analysis showed that the serum cholesterol levels were not associated with the scores of FP.

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Gefitinib Alone or with Concomitant Whole Brain Radiotherapy for Patients with Brain Metastasis from Non-small-cell Lung Cancer: A Retrospective Study

  • Zeng, Yin-Duo;Zhang, Li;Liao, Hai;Liang, Ying;Xu, Fei;Liu, Jun-Ling;Dinglin, Xiao-Xiao;Chen, Li-Kun
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.3
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    • pp.909-914
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    • 2012
  • Background: Gefitinib, a tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR), is used both as a single drug and concurrently with whole brain radiotherapy (WBRT) the standard treatment for brain metastases (BM), and is reported to be effective in a few small studies of patients with BM from non-small-cell lung cancer (NSCLC). However, no study has compared the two treatment modalities. This retrospective analysis was conducted to compare the efficacy of gefitinib alone with gefitinib plus concomitant WBRT in treatment of BM from NSCLC. Methods: We retrospectively reviewed 90 patients with BM from NSCLC who received gefitinib alone (250mg/day, gefitinib group) or with concomitant WBRT (40Gy/20f/4w, gefitinib-WBRT group) between September 2005 and September 2009 at Sun Yat-Sen University Cancer Center. Forty-five patients were in each group. Results: The objective response rate of BM was significantly higher in gefitinib-WBRT group (64.4%) compared with gefitinib group (26.7%, P<0.001). The disease control rate of BM was 71.1% in gefitinib-WBRT group and 42.2% in gefitinib group (P=0.006). The median time to progression of BM was 10.6 months in gefitinib-WBRT group and 6.57 months in gefitinib group (P<0.001). The median overall survival(OS) of gefitinib-WBRT and gefitinib alone group was 23.40 months and 14.83 months, respectively (HR, 0.432, P=0.002). Conclusion: Gefitinib plus concomitant WBRT had higher response rate of BM and significant improvement in OS compared with gefitinib alone in treatment of BM from NSCLC.

Ameliorating Effects of Cheongnoemyeongsin-hwan on Learning and Memory Impairment Induced by Cerebral Hypoperfusion in Rats (청뇌명신환(淸腦明神丸)이 뇌혈류저하 흰쥐의 학습 및 기억 장애 개선에 미치는 영향)

  • Chang, Suk Hee;Hwang, Won Deuk
    • Herbal Formula Science
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    • v.25 no.1
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    • pp.69-87
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    • 2017
  • Objectives : Cheongnoemyeongsin-hwan (CNMSH) is a herb medicine to treat cognitive impairment. This study was investigated the effects of CNMSH on learning and memory impairment induced by cerebral hypoperfusion. Cerebral hypoperfusion was produced chronically by permanent bilateral common carotid artery occlusion (BCCAO) in rats. Methods : CNMSH was administered orally once a day (250 mg/kg) for 28 days starting at 4th week after the BCCAO. The acquisition of learning and the retention of memory were tested on 9th week after the BCCAO using the Morris water maze. In addition, effect of CNMSH on neuronal apoptosis and ${\beta}-amyloid$ accumulation in the hippocmapus was evaluated with immunohistochemistry and Western blotting. Results : 1. CNMSH and ChAL significantly shortened the escape latencies on the 2nd day of acquisition training trials. 2. ChAL significantly prolonged the swimming time spent in the target and peri-target zones and CNMSH also significantly prolonged the swimming time spent in the peri-target zone. 3. CNMSH and ChAL significantly increased the number of target heading in the retention test. 4. ChAL significantly shortened the time of the 1st target heading in the retention test, but CNMSH insignificantly shortened the time of that. 5. CNMSH and ChAL significantly increased the memory score in the retention test. 6. CNMSH and ChAL significantly attenuated the reduction of CA1 neurons, but insignificantly attenuated the reduction of CA1 thickness. 7. CNMSH and ChAL significantly attenuated the up-regulation of Bax expression in the CA1 of hippocampus. 8. CNMSH and ChAL significantly attenuated the up-regulation of cascapse-3 expression in the CA1 of hippocampus. 9. CNMSH and ChAL significantly attenuated the ${\beta}-amyloid$ accumulation in the CA1 of hippocampus. 10. CNMSH and ChAL significantly attenuated the up-regulation of APP expression in the CA1 of hippocampus. 11. CNMSH and ChAL significantly attenuated the up-regulation of BACE-1 expression in the CA1 of hippocampus. Conclusions : The results show that CNMSH attenuates neuronal apoptosis and ${\beta}-amyloid$ accumulation in the hippocampus and alleviates the impairment of learning and memory produced by chronic cerebral hypoperfusion. These results suggest that CNMSH may be a beneficial medicinal herb to treat cognitive impairment associated with neurodegenerative diseases.

Feasibility as a Laundry Detergent Additive of an Alkaline Protease from Bacillus clausii C5 Transformed by Chromosomal Integration (Chromosomal Integration에 의해 제조한 Bacillus clausii C5 유래의 alkaline protease의 세제 첨가제 응용성)

  • Joo, Han-Seung;Choi, Jang Won
    • KSBB Journal
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    • v.27 no.6
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    • pp.352-360
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    • 2012
  • Bacillus clausii I-52 which produced SDS- and $H_2O_2$-tolerant extracellular alkaline protease (BCAP) was isolated from heavily polluted tidal mud flat of West Sea in Incheon, Korea and stable strain (transformant C5) of B. clausii I-52 harboring another copy of BCAP gene in the chromosome was developed using the chromosome integration vector, pHPS9-fuBCAP. When investigated the production of BCAP using B. clausii transformant C5 through pilot-scale submerged fermentation (500 L) at $37^{\circ}C$ for 30 h with an aeration rate of 1 vvm and agitation rate of 250 rpm, protease yield of approximately 105,700 U/mL was achieved using an optimized medium (soybean meal 2%, wheat flour 1%, sodium citrate 0.5%, $K_2HPO_4$ 0.4%, $Na_2HPO_4$ 0.1%, NaCl 0.4%, $MgSO_4{\cdot}7H_2O$ 0.01%, $FeSO_4{\cdot}7H_2O$ 0.05%, liquid maltose 2.5%, $Na_2CO_3$ 0.6%). The enzyme stability of BCAP was increased by addition of polyols (10%, v/v) and also, the stabilities of BCAP towards not only the thermal-induced inactivation at $50^{\circ}C$ but also the SDS and $H_2O_2$-induced inactivation at $50^{\circ}C$ were enhanced. Among the polyols examined, the best result was obtained with propylene glycol (10%, v/v). The BCAP supplemented with propylene glycol exhibited extreme stability against not only the detergent components such as ${\alpha}$-orephin sulfonate (AOS) and zeolite but also the commercial detergent preparations. The granulized enzyme of BCAP was prepared with approximately 1,310,000 U/g of granule. Wash performance analysis using EMPA test fabrics revealed that BCAP granule exhibited high efficiency for removal of protein stains in the presence of anionic surfactants as well as bleaching agents. When compared to Savinase 6T$^{(R)}$ and Everlase 6T$^{(R)}$ manufactured by Novozymes, BCAP under this study probably showed similar or higher efficiency for the removal of protein stains. These results suggest that the alkaline protease produced from B. clausii transformant C5 showing high stability against detergents and high wash performance has significant potential and a promising candidate for use as a detergent additive.

Effect of Acanthopanax Ethanol Extract on Experimental Renal Hypertension in Rats (오가피(五加皮) Ethanol Extract의 실험적(實驗的) 신성고혈압(腎性高血壓)에 미치는 영향(影響))

  • Lee, Sae-Kyu;Ko, Suk-Tai;Lim, Dong-Yoon
    • Journal of Pharmaceutical Investigation
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    • v.8 no.3
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    • pp.16-23
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    • 1978
  • This study was carried out for the purpose of observing the effect of Korean Acanthopanax Radicis Cortex on renal hypertension and to clarify the mechanism of this effect, making use of its ethanol extract. Adult male or female rats, weighing 180-250g, were divided into 3 groups; the first for normotensive control, the second for hypertensive control and the third for hypertensive Acantopanax-treatment. Rats in the normotensive and hypertensive control group were administered 0.9% saline subcutaneously only, whereas those in the Acanthopanax-treated hypertensive group were administered 50mg/kg Acanthopanax ethanol extract subcutanously once a day. Changes of original blood pressure, and responses of blood pressure to various 4gents(norepinephrine, angiotensin, acetylcholine, serotonin and histamine) were recorded for each group on the initial, 18th, 32nd and 46th days of the experiment. The results obtained in this experiment are as follows: 1) The initial blood pressure was $102.6{\pm}7.6mmHg$ on the average. The blood pressures of the normotensive control group were not observed to alter significantly at any period in the course of the experiment. 2) The mean blood pressures in the hypertensive control group were recorded at $120.3{\pm}10.4mmHg$ on the 18th day, at $134.5{\pm}9.2$ on the 32nd day and at $138.8{\pm}8.3$ on the 46th day, thus revealing significant elevation in comparison with the corresponding normotensive control group blood pressures. On the other hand, the mean blood pressures in Acanthopanax-treated hypertensive group on the 18th, 32nd and 46th days were $118.3{\pm}9.7,\;129.9{\pm}8.3\;and\;120.2{\pm}8.3mmHg$ respectively. The blood pressures of the hypertensive-Acanthopanax group recorded. on the 46th day revealed a significant difference as compared with those of the corresponding hypertensive control group. 3) On the 46th day of this experiment, the responses of blood pressure to acetylcholine in the hypertensive-Acanthopanax group were suppressed significantly as compared with those of the hypertensive control group, and in the latter group, angiotensin was decreased markedly as compared with the corresponding normotensive control group. In contrast, pressor action of norepinephrine and depressor action of serotonin and histamine did not differ significantly among the three groups. These results suggest that Acanthopanax ethanol extract suppresses the induction of renal hypertension by means of a cholinergic action such as that caused by acetylcholine.

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The effect of PDGF-BB loaded TCP/chitosan microgranules on new bone formation (혈소판유래성장인자를 함유한 TCP-chitosan 미세과립이 신생골조직 형성에 미치는 영향에 관한 연구)

  • Seol, Yang-Jo;Lee, Jue-Yeon;Kye, Seung-Beom;Lee, Young-Kyu;Kim, Won-Kyeong;Lee, Yong-Moo;Ku, Young;Han, Soo-Boo;Lee, Seung-Jin;Chung, Chong-Pyoung;Rhyu, In-Chul
    • Journal of Periodontal and Implant Science
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    • v.32 no.3
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    • pp.489-500
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    • 2002
  • The purpose of this study was to evaluate newly fabricated tricalcium phosphate(TCP)/chitosan microgranuls as bone substitutes. TCP/chitosan microgranules were fabricated by dropping TCP-chitosan suspension into the NaOH/ethanol solution. The size of microgranules could be controllable via airflow rate. PDGF-BB was loaded into the fabricated granules via freeze-drying methods(300 ng/20 mg). To evaluate cell proliferation, cultured osteoblasts cell lines(MC3T3-El) was dropped on the BioOss(R), chitosan microgranules, TCP/chitosan microgranules and cultured for 1, 7 , 14, and 28 days. Scanning electron microscopic observation was done after 7 days of culture and light microscopic examination was done after 28 days of culture. PDGF-BB release from the microgranules was tested. Rabbit calvarial defects(8 mm in diameter) were formed and chitosan, TCP/chitosan, PDGF-TCP/chitosan microgranules, and BioGran(R) were grafted to test the ability of new bone formation. At SEM view, the size of prepared microgranules was 250-1000 um and TCP powders were observed at the surface of TCP/chitosan microgranules. TCP powders gave roughness to the granules and this might help the attachment of osteoblasts. The pores formed between microgranules might be able to allow new bone ingrowth and vascularization. There were no significant differences in cell number among BioOss(R) and two microgranules at 28 day. Light and scanning electron microscopic examination showed that seeded osteoblastic cells were well attached to TCP/chitosan microgranules and proliferated in a multi-layer. PDGF-BB released from TCP/chitosan microgranules was at therapeutic concentration for at least 1 week. In rabbit calvarial defect models, PDGF-TCP/chitosan microgranules grafted sites showed thicker bone trabeculae pattern and faster bone maturation than others. These results suggested that the TCP/chitosan microgranules showed the potential as bone substitutes.

The Recycling of Nutrient Balance from Small Oranic farming System in Korea (소규모 유기농가단위 경축연계 자원순환 모델연구(I))

  • Yoon, Sung-Hee;Park, Dong-Ha;Choi, Si-Young;Kim, Jeong-Eun
    • Proceedings of the Korean Society of Organic Agriculture Conference
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    • 2009.12a
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    • pp.307-307
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    • 2009
  • 우리나라에서 농가단위 경축순환농업 모델에 대한 조사와 농장내 순환구조에서 양분수지를 조사한 사례도는 미미한 실정이다. 이에 경축연계 자원순환 유기농업농가의 실천사례 발굴하고, 실천모델별 축산형태 및 경종형태를 조사하여 경종부분의 양분순환과 양분수지를 조사하고자 하였다. 발굴된 농가단위 경축순환농업 사례는 3가지 형태로 모두 한우를 11~21두 범위에서 사육하는 동시에 $15,510m^2$의 밭농사를 수행하는 농가, $8,019m^2$의 밭농사와 $8,250m^2$ 논농사를 동시에 수행하는 농가, $26,400m^2$의 논농사만 수행하는 농가들이었다. 각 모델에서 배합사료는 모두 외부에서 구입하고 있었으며 조사료의 자급율은 25 ~ 100%인 것으로 조사되었다. 특히, 한우 20두와 논농사 $26,400m^2$를 경영하는 농가에서 조사료(볏짚)의 100%를 자급하였고 동시에 한우사육과정에서 발생한 자급퇴비를 전량 논농사에 사용하여 유기농 벼농사를 유지하고 있었다. 밭농사를 함께 수행하는 농가에서는 자급퇴비 외에 외부로부터 유박비료 및 발효유기질비료를 구입하여 양분을 충당하고 있었다. 각 농가의 토양이화학성을 분석한 결과 pH는 5.49~7.61, 유기물 함량은 1.37~1.40%, 유효인산 함량 253.32~329.63 mg/kg, 칼륨 0.24~0.3, 칼슘 3.97~10.1, 마그네슘 0.89~1.77 $Cmol^+$/kg, CEC는 7.92~11 $Cmol^+$/kg 이었므며 토양내 잔류농약은 검출되지 않았다. 농가별로 발생한 우분퇴비의 성분 분석결과는 전질소 0.68 ~ 0.73%, 전인산 0.68 ~ 0.86%, 칼륨 0.70~0.78% 수준이었다. 각 사례농가별 투입한 실제시비량, 토양분석결과와 사용된 자재의 성분 분석결과를 이용한 시비처방법에 따른 시비량 및 표준시비법에 따른 시비량을 산출하여 3요소의 양분수지를 계산하였다. 이와 함께 유기질비료의 무기화율을 감안한 시비량도 산출하였다. 양분수지를 분석한 결과 3농가 모두 실제시비량은 3요소 모두 초과 되는 것으로 나타났으며, 특히 인산과 칼륨이 2배정도 초과되는 경향을 보였다. 그러나 투입된 자급퇴비 및 유기질비료의 무기화율을 감안한 시비량으로 환산할 경우에는 질소성분이 3농가 모두 부족한 것으로 산출되었으며, 인산과 가리 성분은 충분하거나 초과되는 것으로 계산되었다. 농장내 축산경영을 통해 발생하는 자급퇴비만을 이용할 경우에 경종부문의 양분수지를 산출한 결과를 보면 실제시비량 기준으로 질소는 56~186%, 인산은 90~346%, 칼륨은41~221%로 양분수지가 달라졌으며, 무기화를 감안한 기준으로는 질소는 16~53%, 인산은 52~197%, 칼륨은 41~221%로 양분수지가 달라졌다. 소규모 유기농가단위 경축연계 자원순환 모델 연구를 통해 유기경종농업이 유지될 수 있으나, 3요소별 양분수지의 불균형이 발생할 수 있는 것으로 조사되었으며, 유기질비료의 특성상 무기화율을 감안한 시비량을 적용할 경우에는 질소 성분의 부족과 동시에 인산, 칼륨 성분의 과다가 예측되었다. 따라서 이러한 성분의 불균형을 조정할 시비체계 연구가 필요한 것으로 판단되었다. 본 연구는 농촌진흥청의 "유기가축사양 및 유기 순환체계모델" 연구사업의 세부과제로 수행한 1년차 결과입니다.

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Effects of Samjung-hwan($S{\={a}}nj{\={i}}ngw{\'{a}}n$) on Obesity and Lipid Metabolism In Rats with High Fat Diet (삼정환(三精丸)이 고지방(高脂肪) 식이(食餌) 흰 쥐의 비만에 미치는 영향)

  • Kim, Ji-Hyung;Kim, Geun-Woo;Koo, Byung-Soo
    • Journal of Oriental Neuropsychiatry
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    • v.20 no.2
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    • pp.47-60
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    • 2009
  • Objectives : This study was performed to show the effects of Samjung-hwan ($S{\={a}}nj{\={i}}ngw{\'{a}}n$) extract on obesity and lipid metabolism of rats fed high fat diet. Methods : Crushed Samjung-hwan($S{\={a}}nj{\={i}}ngw{\'{a}}n$) 245 g was extracted with methyl alcohol. The extract was evaporated under reduced pressure to give 21.8 g. 20 rats were divided into normal, control, and two test groups. For 6 weeks, The normal group rats were supplied with a normal diet. The control group rats were supplied with a high fat diet. The test group 1 rats were supplied with a high fat diet and Samjung-hwan($S{\={a}}nj{\={i}}ngw{\'{a}}n$) extract 250 rug/kg and the test group 2 rats were supplied witha high fat diet and Samjunghwan($S{\={a}}nj{\={i}}ngw{\'{a}}n$) extract 500 mg/kg. Results : 1) The control group rats showed significantly increased weight of peritoneal fat than the nornal group rats. The test group 1 rats did not show significant difference compare to the control group rats, and the test group 2 rats showed significantly decreased weight of peritoneal fat than the control group rats. 2) The control group rats showed significantly increased triglyceride than the nornal group rats. The test group 1 rats showed significantly decreased triglyceride than the control group rats, and the test group 2 rats showed significantly decreased triglyceride than the control group rats. 3) The control group rats showed significantly increased LDL-cholesterol than the nornal group rats. The test group 1 rats showed significantly decreased LDL-cholesterol than the control group rats, and the test group 2 rats did not show significant difference compare to the control group rats. Conclusions : These results suggest that effectiveness of Samjung-hwan($S{\={a}}nj{\={i}}ngw{\'{a}}n$) extract to control the obesity and abnormal lipid metabolism caused by a high fat diet.

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Molecular Mechanism of Tetrabromobisphenol A (TBBPA)-induced Target Organ Toxicity in Sprague-Dawley Male Rats

  • Choi, Jae-Seok;Lee, Young-Jun;Kim, Tae-Hyung;Lim, Hyun-Jung;Ahn, Mee-Young;Kwack, Seung-Jun;Kang, Tae-Seok;Park, Kui-Lea;Lee, Jae-Won;Kim, Nam-Deuk;Jeong, Tae-Cheon;Kim, Sang-Geum;Jeong, Hye-Gwang;Lee, Byung-Mu;Kim, Hyung-Sik
    • Toxicological Research
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    • v.27 no.2
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    • pp.61-70
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    • 2011
  • Brominated flame retardants (BFRs) are present in many consumer products ranging from fabrics to plastics and electronics. Wide use of flame retardants can pose an environmental hazard, which makes it important to determine the mechanism of their toxicity. In the present study, dose-dependent toxicity of tetrabromobisphenol A (TBBPA), a flame retardant, was examined in male prepubertal rats (postnatal day 18) treated orally with TBBPA at 0, 125, 250 or 500 mg/kg for 30 days. There were no differences in body weight gain between the control and TBBPA-treated groups. However, absolute and relative liver weights were significantly increased in high dose of TBBPA-treated groups. TBBPA treatment led to significant induction of CYP2B1 and constitutive androstane receptor (CAR) expression in the liver. In addition, serum thyroxin (T4) concentration was significantly reduced in the TBBPA treated group. These results indicate that repeated exposure to TBBPA induces drug-metabolising enzymes in rats through the CAR signaling pathway. In particular, TBBPA efficiently produced reactive oxygen species (ROS) through CYP2B1 induction in rats. We measured 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of DNA oxidative damage, in the kidney, liver and testes of rats following TBBPA treatment. As expected, TBBPA strongly induced the production of 8-OHdG in the testis and kidney. These observations suggest that TBBPA-induced target organ toxicity may be due to ROS produced by metabolism of TBBPA in Sprague-Dawley rats.