Purpose: $^{99m}Tc$-sestamibi(MIBI) and $^{99m}Tc$-tetrofosmin have been used as substrates for P-glycoprotein (Pgp) and multidrug resistance associated protein (MRP), which are closely associated with multidrug resistance of the tumors. To understand different handling of radiotracers in cancer cell lines expressing Pgp and MRP, we compared cellular uptakes of $^{99m}Tc$-MIBI and $^{99m}Tc$-tetrofosmin. The effects of cyclosporin A (CsA), well-known multidrug resistant reversing agent, on the uptake of both tracers were also compared. Materials and Methods: HCT15/CL02 human colorectal cancer cells for Pgp expressing cells, and human non-small cell lung cancer A549 cells for MRP expressing cells, were used for in vitro and in vivo studies. RT-PCR, western blot analysis and immunohistochemistry were used for detection of Pgp and MRP. MDR-reversal effect with CsA was evaluated at different drug concentrations after incubation with MIBI or tetrofosmin. Radioactivities of supernatant and pellet were measured with gamma well counter. Tumoral uptake of the tracers were measured from tumor bearing nude mice treated with or without CsA. Results: RT-PCR, western blot analysis of the cells and irnrnunochemical staining revealed selective expression of Pgp and MRP for HCY15/CL02 and A549 cells, respectively. There were no significant difference in cellular uptakes of both tracers in HCT15/CL02 cells, but MIBI uptake was slightly higher than that of tetrofosmin in A549 cells. Co-incubation with CsA resulted in a increase in cellular uptakes of MIBI and tetrofosmin. Uptake of MIBI or tetrofosmin in HCT15/CL02 cells was increased by 10- and 2.4-fold, and by 7.5 and 6.3-fold in A549 cells, respectively. Percentage increase of MIBI was higher than that of tetrofosmin with CsA for both cells (p<0.05). In vivo biodistribution study showed that MIBI (114% at 10 min, 257% at 60 min, 396% at 240 min) and tetrofosmin uptake (110% at 10 min, 205% at 60 min, 410% at 240 min) were progressively increased by the time, up to 240 min with CsA. But increases in tumoral uptake were not significantly different between MIBI and tetrofosmin for both tumors. Conclusion: MIBI seems to be a better tracer than tetrofosmin for evaluating MDR reversal effect of the modulators in vitro, but these differences were not evident in vivo tumoral uptake. Both MIBI and tetrofosmin seem to be suitable tracers for imaging Pgp- and MRP-mediated drug resistance in tumors.
This study was conducted to provide exportation strategy by surveying on preference of Japanese consumers on cut chrysanthemum exported. The survey was conducted two times by a local survey company in Japan, and the surveys were conducted largely on chrysanthemums for casual flowers and the altar. After departmentalizing Japanese consumers per groups the result were analyzed through conjoint and cluster methods, flower colors and shape were used relatively higher rate for selection criteria of flowers in every group in the case of casual flowers. Group 1 comprised of 60 year-old housewives who reside in a small city with high school diploma and annual income less than 300 million yen, and group 2 of 40 year-old housewives who are small city residents with high school diplomas and annual income of 300 million yen show higher rate of use in flower shape than colors. Another group 3 whose members are 50 year-old housewives, small city residents with high school diplomas and annual income of 600 million yen showed higher rate of use colors than the shape for selection criteria of flowers. The consumption characteristics according to the ages of the consumers showed a pronounced tendency. The 40-50 year-old housewives preferred single flowers packed with other flowers, and the 60 year-old housewives double flowers packed with only chrysanthemums. In flower color, the 50-60 year-old housewives preferred white and yellow flowers, and the 40 year-old housewives pink and yellow flowers. Therefore, there are needs for development strategy of new products considering the consumption characteristics of flower shape and color according to the ages of consumer. After analyzing the chrysanthemums for altar by departmentalization of Japanese consumers, every group showed relative higher rate of use for flower shape for selection criteria of flowers. According to the analysis on the consumption characteristics, group 1 which is comprised of 30-40 year-old housewives who reside in small city with high school diplomas and income less than 300 million yen, and the group 2 of 20 year-old housewives who reside in small city with college diplomas and annual income less than 300 million yen. They are very sensitive to the price of the products while the group 3 of 50 year-old housewives who reside in small city with high school diplomas and annual income less than 300 million yen are insensitive to the price. The 30-50 year-old housewives preferred white and pink flowers, and the 20 year-old housewives yellow and pink flowers. In flower shape, the 50 year-old housewives preferred anemone shape, the 30-40 year-old housewives double shape, and the 20 year-old housewives pompon shapes. Therefore, the white, double flowers for the 30-40 year-old housewives and the yellow, pompon flowers for the 20 year-old housewives are needed to be created at the lowest cost, while the white, anemone flowers are needed to created at higher cost with high quality. In light of these results, it is considered that we should understand the types of purchasing products through consumption characteristics of Japanese consumers. Also we should plan, create market-oriented and consumer-oriented products, and should export them in order to expand more exportation.
Ha, Ji Hoon;Jeong, Yoon Ju;Seong, Joon Seob;Kim, Kyoung Mi;Kim, A Young;Fu, Min Min;Suh, Ji Young;Lee, Nan Hee;Park, Jino;Park, Soo Nam
Journal of the Society of Cosmetic Scientists of Korea
/
v.41
no.4
/
pp.361-373
/
2015
This study was carried out to evaluate the antioxidant and antibacterial activities of Glycyrriza uralensis Fisher (Jecheon, Korea) extracts obtained by various extraction conditions (85% ethanol, heating temperatures and times), and to establish the optimal extraction condition of G. uralensis for the application as cosmetic ingredients. The extracts obtained under different conditions were concentrated and made in the powdered (sample-1) and were the crude extract solutions without concentration (sample-2). The antioxidant effects were determined by free radical scavenging activity ($FSC_{50}$), ROS scavenging activity ($OSC_{50}$), and cellular protective effects. Antibacterial activity was determined by minimum inhibitory concentration (MIC) on human skin flora. DPPH free radical scavenging activity of sample-1 ($100{\mu}g/mL$) was 10% higher in group extracted for 6 h than 12 h, but sample-2 didn't show any significant differences. The extraction yield extracted with same temperature for 12 h was 2.6 times higher than 6 h, but total flavonoid content was 1.1 times higher. These results indicated that total flavonoid content hardly increased with increasing extraction time. Free radical scavenging activity, ROS scavenging activity and cellular protective effects were not dependent on the yield of extraction, but total flavonoid content of extraction. Antibacterial activity on three skin flora (S. aureus, B. subtilis, P. acnes)of sample-1 in different extraction conditions were evaluated on same concentration, and the group extracted at 25 and $40^{\circ}C$ showed 16 times higher than methyl paraben ($2,500{\mu}g/mL$). In conclusion, 85% ethanol extracts of G. uralensis extracted at $40^{\circ}C$ for 6 h showed the highest antioxidant and antibacterial activity. These results indicate that the extraction condition is important to be optimized by comprehensive evaluation of extraction yield with various conditions, yield of active component, and activity test with concentrations, and activity of 100% extract, for manufacturing process of products.
Background : We have recently reported that airway epithelial cells can produce RANTES and IL-8 in response to the stimulation of tubercle bacilli suggesting a certain role of airway epithelial cells in the pathogenesis of pulmonary tuberculosis. The pathogenesis of tuberculosis is determined by several factors including phagocytosis, immunological response of host, and virulence of tubercle bacilli. Interestingly, there have been reports suggesting that difference in immunological response of host according to the virulence of tubercle bacilli may be related with the pathogenesis of tuberculosis. We, therefore, studied the expressions and productions of RANTES and IL-8 in airway epithelial cells in response to tubercle bacilli(H37Rv, virulent strain and H37Ra, avirulent strain), in order to elucidate the possible pathophysiology of pulmonary tuberculosis. Methods : Peripheral blood monocytes were isolated from normal volunteers. Peripheral blood monocytes (PBM) were stimulated with LPS($10{\mu}g/ml$), H37Rv, or H37Ra($5{\times}10^5$ bacilli/well) along with normal control for 24 hours. A549 cells were stimulated with supernatants of cultured PBM for 24 hours. ELISA kit was used for the measurement of $TNF{\alpha}$ and IL-$1{\beta}$ production in supernatants of cultured PBM and for the measurement of RANTES and IL-8 in supernatants of cultured A549 cells. Northern blot analysis was used for the measurement of RANTES and IL-8 mRNA expression in cultured A549 cells. Results : $TNF{\alpha}$ and IL-$1{\beta}$ productions were increased in cultured PBM stimulated with LPS or tubercle bacilli(H37Rv or H37Ra) compared with the control. There was, however, no difference in $TNF{\alpha}$ and IL-$1{\beta}$ production between cultured PBM stimulated with H37Rv and H37Ra. RANTES and IL-8 expressions and productions were also increased in cultured A549 cells stimulated with LPS or tubercle bacilli compared with the control. RANTES and IL-8 mRNA expressions were significantly increased in cultured A549 cells stimulated with H37Ra-conditioned media(CM) compared with A549 cells stimulated with H37Rv-CM (p<0.05). However, there was no difference in RANTES and IL-8 productions between A549 cells stimulated with H37Rv-CM and H37Ra-CM. Conclusion : Airway epithelial cells can produce the potent chemokines such as RANTES and IL-8, in response to the stimulation of tubercle bacilli. These results suggest that airway epithelial cells may play a certain role in the pathogenesis of pulmonary tuberculosis. However, the role of airway epithelial cells in the pathogenesis of tuberculosis according to the virulence of tubercle bacilli was not clear in this study.
Purpose: Bone metastasis in breast cancer patients are usually assessed by conventional Tc-99m methylene diphosphonate whole-body bone scan, which has a high sensitivity but a poor specificity. However, positron emission tomography with $^{18}F-2-deoxyglucose$ (FDG-PET) can offer superior spatial resolution and improved specificity. FDG-PET/CT can offer more information to assess bone metastasis than PET alone, by giving a anatomical information of non-enhanced CT image. We attempted to evaluate the usefulness of FDG-PET/CT for detecting bone metastasis in breast cancer and to compare FDG-PET/CT results with bone scan findings. Materials and Methods: The study group comprised 157 women patients (range: $28{\sim}78$ years old, $mean{\pm}SD=49.5{\pm}8.5$) with biopsy-proven breast cancer who underwent bone scan and FDG-PET/CT within 1 week interval. The final diagnosis of bone metastasis was established by histopathological findings, radiological correlation, or clinical follow-up. Bone scan was acquired over 4 hours after administration of 740 MBq Tc-99m MDP. Bone scan image was interpreted as normal, low, intermediate or high probability for osseous metastasis. FDG PET/CT was performed after 6 hours fasting. 370 MBq F-18 FDG was administered intravenously 1 hour before imaging. PET data was obtained by 3D mode and CT data, used as transmission correction database, was acquired during shallow respiration. PET images were evaluated by visual interpretation, and quantification of FDG accumulation in bone lesion was performed by maximal SUV(SUVmax) and relative SUV(SUVrel). Results: Six patients(4.4%) showed metastatic bone lesions. Four(66.6%) of 6 patients with osseous metastasis was detected by bone scan and all 6 patients(100%) were detected by PET/CT. A total of 135 bone lesions found on either FDG-PET or bone scan were consist of 108 osseous metastatic lesion and 27 benign bone lesions. Osseous metastatic lesion had higher SUVmax and SUVrel compared to benign bone lesion($4.79{\pm}3.32$ vs $1.45{\pm}0.44$, p=0.000, $3.08{\pm}2.85$ vs $0.30{\pm}0.43$, p=0.000). Among 108 osseous metastatic lesions, 76 lesions showed as abnormal uptake on bone scan, and 76 lesions also showed as increased FDG uptake on PET/CT scan. There was good agreement between FDG uptake and abnormal bone scan finding (Kendall tau-b : 0.689, p=0.000). Lesion showed increased bone tracer uptake had higher SUVmax and SUVrel compared to lesion showed no abnormal bone scan finding ($6.03{\pm}3.12$ vs $1.09{\pm}1.49$, p=0.000, $4.76{\pm}3.31$ vs $1.29{\pm}0.92$, p=0.000). The order of frequency of osseous metastatic site was vertebra, pelvis, rib, skull, sternum, scapula, femur, clavicle, and humerus. Metastatic lesion on skull had highest SUVmax and metastatic lesion on rib had highest SUVrel. Osteosclerotic metastatic lesion had lowest SUVmax and SUVrel. Conclusion: These results suggest that FDG-PET/CT is more sensitive to detect breast cancer patients with osseous metastasis. CT scan must be reviewed cautiously skeleton with bone window, because osteosclerotic metastatic lesion did not showed abnormal FDG accumulation frequently.
Background : Isoniazid(INH) and rifampicin(RFP) are potent antituberculous drugs which have made tuberculous disease become decreasing. In Korea, prescribed doses of INH and RFP have been different from those recommended by American Thoracic Society. In fact they were determined by clinical experience rather than by scientific basis. Even there has been. few reports about pharmacokintic parameters of INH and RFP in healthy Koreans. Method : Oral pharmacokinetics of INH were studied in 22 healthy native Koreans after administration of 300 mg and 400mg of INH to each same person successively at least 2 weeks apart. After an overnight fast, subjects received medication and blood samples were drawn at scheduled times over a 24-hour period. Urine collection was also done for 24 hours. Pharmacokinetics of RFP were studied in 20 subjects in a same fashion with 450mg and 600mg of RFP. Plasma and urinary concentrations of INH and RFP were determined by high-performance liquid chromatography(HPLC). Results : Time to reach peak serum concentration (Tmax) of INH was $1.05{\pm}0.34\;hrs$ at 300mg dose and $0.98{\pm}0.59\;hrs$ at 400mg dose. Half-life was $2.49{\pm}0.88\;hrs$ and $2.80{\pm}0.75\;hrs$, respectively. They were not different significantly(p > 0.05). Peak serum concentration(Cmax) after administration of 400mg of INH was $7.14{\pm}1.95mcg/mL$ which was significantly higher than Cmax ($4.37{\pm}1.28mcg/mL$) by 300mg of INH(p < 0.01). Total clearance(CLtot) of INH at 300mg dose was $26.76{\pm}11.80mL/hr$. At 400mg dose it was $21.09{\pm}8.31mL/hr$ which was significantly lower(p < 0.01) than by 300mg dose. While renal clearance(CLr) was not different among two groups, nonrenal clearance(CLnr) at 400mg dose ($18.18{\pm}8.36mL/hr$) was significantly lower than CLnr ($23.71{\pm}11.52mL/hr$) by 300mg dose(p < 0.01). Tmax of RFP was $1.11{\pm}0.41\;hrs$ at 450mg dose and $1.15{\pm}0.43\;hrs$ at 600mg dose. Half-life was $4.20{\pm}0.73\;hrs$ and $4.95{\pm}2.25\;hrs$, respectively. They were not different significantly(p > 0.05). Cmax after administration of 600mg of RFP was $13.61{\pm}3.43mcg/mL$ which was significantly higher than Cmax($10.12{\pm}2.25mcg/mL$) by 450mg of RFP(p < 0.01). CLtot of RFP at 450mg dose was $7.60{\pm}1.34mL/hr$. At 600mg dose it was $7.05{\pm}1.20mL/hr$ which was significantly lower(p < 0.05) than by 450mg dose. While CLr was not different among two groups, CLnr at 600 mg dose($5.36{\pm}1.20mL/hr$) was significantly lower than CLnr($6.19{\pm}1.56mL/hr$) by 450mg dose(p < 0.01). Conclusion : Considering Cmax and CLnr, 300mg, of INH and 450mg RFP might be sufficient doses for the treatment of tuberculosis in Koreans. But it remains to be clarified in the patients with tuberculosis.
본 웹사이트에 게시된 이메일 주소가 전자우편 수집 프로그램이나
그 밖의 기술적 장치를 이용하여 무단으로 수집되는 것을 거부하며,
이를 위반시 정보통신망법에 의해 형사 처벌됨을 유념하시기 바랍니다.
[게시일 2004년 10월 1일]
이용약관
제 1 장 총칙
제 1 조 (목적)
이 이용약관은 KoreaScience 홈페이지(이하 “당 사이트”)에서 제공하는 인터넷 서비스(이하 '서비스')의 가입조건 및 이용에 관한 제반 사항과 기타 필요한 사항을 구체적으로 규정함을 목적으로 합니다.
제 2 조 (용어의 정의)
① "이용자"라 함은 당 사이트에 접속하여 이 약관에 따라 당 사이트가 제공하는 서비스를 받는 회원 및 비회원을
말합니다.
② "회원"이라 함은 서비스를 이용하기 위하여 당 사이트에 개인정보를 제공하여 아이디(ID)와 비밀번호를 부여
받은 자를 말합니다.
③ "회원 아이디(ID)"라 함은 회원의 식별 및 서비스 이용을 위하여 자신이 선정한 문자 및 숫자의 조합을
말합니다.
④ "비밀번호(패스워드)"라 함은 회원이 자신의 비밀보호를 위하여 선정한 문자 및 숫자의 조합을 말합니다.
제 3 조 (이용약관의 효력 및 변경)
① 이 약관은 당 사이트에 게시하거나 기타의 방법으로 회원에게 공지함으로써 효력이 발생합니다.
② 당 사이트는 이 약관을 개정할 경우에 적용일자 및 개정사유를 명시하여 현행 약관과 함께 당 사이트의
초기화면에 그 적용일자 7일 이전부터 적용일자 전일까지 공지합니다. 다만, 회원에게 불리하게 약관내용을
변경하는 경우에는 최소한 30일 이상의 사전 유예기간을 두고 공지합니다. 이 경우 당 사이트는 개정 전
내용과 개정 후 내용을 명확하게 비교하여 이용자가 알기 쉽도록 표시합니다.
제 4 조(약관 외 준칙)
① 이 약관은 당 사이트가 제공하는 서비스에 관한 이용안내와 함께 적용됩니다.
② 이 약관에 명시되지 아니한 사항은 관계법령의 규정이 적용됩니다.
제 2 장 이용계약의 체결
제 5 조 (이용계약의 성립 등)
① 이용계약은 이용고객이 당 사이트가 정한 약관에 「동의합니다」를 선택하고, 당 사이트가 정한
온라인신청양식을 작성하여 서비스 이용을 신청한 후, 당 사이트가 이를 승낙함으로써 성립합니다.
② 제1항의 승낙은 당 사이트가 제공하는 과학기술정보검색, 맞춤정보, 서지정보 등 다른 서비스의 이용승낙을
포함합니다.
제 6 조 (회원가입)
서비스를 이용하고자 하는 고객은 당 사이트에서 정한 회원가입양식에 개인정보를 기재하여 가입을 하여야 합니다.
제 7 조 (개인정보의 보호 및 사용)
당 사이트는 관계법령이 정하는 바에 따라 회원 등록정보를 포함한 회원의 개인정보를 보호하기 위해 노력합니다. 회원 개인정보의 보호 및 사용에 대해서는 관련법령 및 당 사이트의 개인정보 보호정책이 적용됩니다.
제 8 조 (이용 신청의 승낙과 제한)
① 당 사이트는 제6조의 규정에 의한 이용신청고객에 대하여 서비스 이용을 승낙합니다.
② 당 사이트는 아래사항에 해당하는 경우에 대해서 승낙하지 아니 합니다.
- 이용계약 신청서의 내용을 허위로 기재한 경우
- 기타 규정한 제반사항을 위반하며 신청하는 경우
제 9 조 (회원 ID 부여 및 변경 등)
① 당 사이트는 이용고객에 대하여 약관에 정하는 바에 따라 자신이 선정한 회원 ID를 부여합니다.
② 회원 ID는 원칙적으로 변경이 불가하며 부득이한 사유로 인하여 변경 하고자 하는 경우에는 해당 ID를
해지하고 재가입해야 합니다.
③ 기타 회원 개인정보 관리 및 변경 등에 관한 사항은 서비스별 안내에 정하는 바에 의합니다.
제 3 장 계약 당사자의 의무
제 10 조 (KISTI의 의무)
① 당 사이트는 이용고객이 희망한 서비스 제공 개시일에 특별한 사정이 없는 한 서비스를 이용할 수 있도록
하여야 합니다.
② 당 사이트는 개인정보 보호를 위해 보안시스템을 구축하며 개인정보 보호정책을 공시하고 준수합니다.
③ 당 사이트는 회원으로부터 제기되는 의견이나 불만이 정당하다고 객관적으로 인정될 경우에는 적절한 절차를
거쳐 즉시 처리하여야 합니다. 다만, 즉시 처리가 곤란한 경우는 회원에게 그 사유와 처리일정을 통보하여야
합니다.
제 11 조 (회원의 의무)
① 이용자는 회원가입 신청 또는 회원정보 변경 시 실명으로 모든 사항을 사실에 근거하여 작성하여야 하며,
허위 또는 타인의 정보를 등록할 경우 일체의 권리를 주장할 수 없습니다.
② 당 사이트가 관계법령 및 개인정보 보호정책에 의거하여 그 책임을 지는 경우를 제외하고 회원에게 부여된
ID의 비밀번호 관리소홀, 부정사용에 의하여 발생하는 모든 결과에 대한 책임은 회원에게 있습니다.
③ 회원은 당 사이트 및 제 3자의 지적 재산권을 침해해서는 안 됩니다.
제 4 장 서비스의 이용
제 12 조 (서비스 이용 시간)
① 서비스 이용은 당 사이트의 업무상 또는 기술상 특별한 지장이 없는 한 연중무휴, 1일 24시간 운영을
원칙으로 합니다. 단, 당 사이트는 시스템 정기점검, 증설 및 교체를 위해 당 사이트가 정한 날이나 시간에
서비스를 일시 중단할 수 있으며, 예정되어 있는 작업으로 인한 서비스 일시중단은 당 사이트 홈페이지를
통해 사전에 공지합니다.
② 당 사이트는 서비스를 특정범위로 분할하여 각 범위별로 이용가능시간을 별도로 지정할 수 있습니다. 다만
이 경우 그 내용을 공지합니다.
제 13 조 (홈페이지 저작권)
① NDSL에서 제공하는 모든 저작물의 저작권은 원저작자에게 있으며, KISTI는 복제/배포/전송권을 확보하고
있습니다.
② NDSL에서 제공하는 콘텐츠를 상업적 및 기타 영리목적으로 복제/배포/전송할 경우 사전에 KISTI의 허락을
받아야 합니다.
③ NDSL에서 제공하는 콘텐츠를 보도, 비평, 교육, 연구 등을 위하여 정당한 범위 안에서 공정한 관행에
합치되게 인용할 수 있습니다.
④ NDSL에서 제공하는 콘텐츠를 무단 복제, 전송, 배포 기타 저작권법에 위반되는 방법으로 이용할 경우
저작권법 제136조에 따라 5년 이하의 징역 또는 5천만 원 이하의 벌금에 처해질 수 있습니다.
제 14 조 (유료서비스)
① 당 사이트 및 협력기관이 정한 유료서비스(원문복사 등)는 별도로 정해진 바에 따르며, 변경사항은 시행 전에
당 사이트 홈페이지를 통하여 회원에게 공지합니다.
② 유료서비스를 이용하려는 회원은 정해진 요금체계에 따라 요금을 납부해야 합니다.
제 5 장 계약 해지 및 이용 제한
제 15 조 (계약 해지)
회원이 이용계약을 해지하고자 하는 때에는 [가입해지] 메뉴를 이용해 직접 해지해야 합니다.
제 16 조 (서비스 이용제한)
① 당 사이트는 회원이 서비스 이용내용에 있어서 본 약관 제 11조 내용을 위반하거나, 다음 각 호에 해당하는
경우 서비스 이용을 제한할 수 있습니다.
- 2년 이상 서비스를 이용한 적이 없는 경우
- 기타 정상적인 서비스 운영에 방해가 될 경우
② 상기 이용제한 규정에 따라 서비스를 이용하는 회원에게 서비스 이용에 대하여 별도 공지 없이 서비스 이용의
일시정지, 이용계약 해지 할 수 있습니다.
제 17 조 (전자우편주소 수집 금지)
회원은 전자우편주소 추출기 등을 이용하여 전자우편주소를 수집 또는 제3자에게 제공할 수 없습니다.
제 6 장 손해배상 및 기타사항
제 18 조 (손해배상)
당 사이트는 무료로 제공되는 서비스와 관련하여 회원에게 어떠한 손해가 발생하더라도 당 사이트가 고의 또는 과실로 인한 손해발생을 제외하고는 이에 대하여 책임을 부담하지 아니합니다.
제 19 조 (관할 법원)
서비스 이용으로 발생한 분쟁에 대해 소송이 제기되는 경우 민사 소송법상의 관할 법원에 제기합니다.
[부 칙]
1. (시행일) 이 약관은 2016년 9월 5일부터 적용되며, 종전 약관은 본 약관으로 대체되며, 개정된 약관의 적용일 이전 가입자도 개정된 약관의 적용을 받습니다.