• 제목/요약/키워드: Endocrine effect

검색결과 365건 처리시간 0.029초

TM-25659-Induced Activation of FGF21 Level Decreases Insulin Resistance and Inflammation in Skeletal Muscle via GCN2 Pathways

  • Jung, Jong Gab;Yi, Sang-A;Choi, Sung-E;Kang, Yup;Kim, Tae Ho;Jeon, Ja Young;Bae, Myung Ae;Ahn, Jin Hee;Jeong, Hana;Hwang, Eun Sook;Lee, Kwan-Woo
    • Molecules and Cells
    • /
    • 제38권12호
    • /
    • pp.1037-1043
    • /
    • 2015
  • The TAZ activator 2-butyl-5-methyl-6-(pyridine-3-yl)-3-[2'-(1H-tetrazole-5-yl)-biphenyl-4-ylmethyl]-3H-imidazo[4,5-b]pyridine] (TM-25659) inhibits adipocyte differentiation by interacting with peroxisome proliferator-activated receptor gamma. 1 TM-25659 was previously shown to decrease weight gain in a high fat (HF) diet-induced obesity (DIO) mouse model. However, the fundamental mechanisms underlying the effects of TM-25659 remain unknown. Therefore, we investigated the effects of TM-25659 on skeletal muscle functions in C2 myotubes and C57BL/6J mice. We studied the molecular mechanisms underlying the contribution of TM-25659 to palmitate (PA)-induced insulin resistance in C2 myotubes. TM-25659 improved PA-induced insulin resistance and inflammation in C2 myotubes. In addition, TM-25659 increased FGF21 mRNA expression, protein levels, and FGF21 secretion in C2 myotubes via activation of GCN2 pathways (GCN2-$phosphoelF2{\alpha}$-ATF4 and FGF21). This beneficial effect of TM-25659 was diminished by FGF21 siRNA. C57BL/6J mice were fed a HF diet for 30 weeks. The HF-diet group was randomly divided into two groups for the next 14 days: the HF-diet and HF-diet + TM-25659 groups. The HF diet + TM-25659-treated mice showed improvements in their fasting blood glucose levels, insulin sensitivity, insulin-stimulated Akt phosphorylation, and inflammation, but neither body weight nor food intake was affected. The HF diet + TM-25659-treated mice also exhibited increased expression of both FGF21 mRNA and protein. These data indicate that TM-25659 may be beneficial for treating insulin resistance by inducing FGF21 in models of PA-induced insulin resistance and HF diet-induced insulin resistance.

홍삼 사포닌이 랫드의 다낭성난소에 미치는 영향 (Effects of Red Ginseng Total Saponin on the Polycystic Ovaries in Rats)

  • 이지애;임성철;류애란;배진규;강성수;김종춘;김성호;김정욱;최범채;배춘식
    • KSBB Journal
    • /
    • 제19권6호
    • /
    • pp.433-436
    • /
    • 2004
  • 홍삼 사포닌이 estradiol valerate로 유발된 랫드의 다낭성난소에 미치는 영향을 관찰한 결과 다음과 같은 결론을 얻었다. 1. 홍삼 사포닌을 투여한 실험군의 난소형태는 퇴축난포, 정상발달을 보이는 이차난포 및 황체형성 등 비교적 정상화된 난소의 소견이 관찰되어 다낭성난소의 현저한 치료 효과를 보였다. 2. 홍삼 사포닌을 투여한 실험군의 신경성장인자 염색은 대조군에 비해 난소조직에서 내협막 세포들과 간질세포들이 현저하게 감소된 현상을 보였으나, 뇌하수체 및 해마체에서는 뚜렷한 차이가 없는 것으로 관찰되었다. 이상의 결과를 종합해보면 홍삼 사포닌은 다낭성난소 증후군의 예방 및 치료에 효과가 있을 것으로 사료된다.

Nonmonotonic Effects of Chronic Low-Dose Di(2-ethylhexyl) Phthalate on Gonadal Weight and Reproduction

  • Cha, Sunyeong;Jung, Kayeon;Lee, Min Young;Hwang, Yeon Jeong;Yang, Eunhyeok;Lee, Sung-Ho;Jung, Hyo-il;Cheon, Yong-Pil
    • 한국발생생물학회지:발생과생식
    • /
    • 제22권1호
    • /
    • pp.85-94
    • /
    • 2018
  • Endocrine disruptors have been concerned in toxicology but now challenged as physiological point especially concerned with exposing dose and period. In this study the low-dose chronic administration of di(2-ethylhexyl) phthaltae (DEHP) during reproductive period was examined to evaluate the possible roles. Adult male and female CD-1 mice were exposed to DEHP with drinking water containing $133{\mu}g/L$ and $1,330{\mu}g/L$ DEHP in water according to OECD 433 guide line and sacrificed just after weaning. The weights of uterus and ovary were decreased by drinking of $1,330{\mu}g/L$ DEHP water. There was not adverse effects on either accumulated mating rate and mating rate depend on estrus stage, pregnancy duration, and sex ration at birth. However, the accumulated rate of successful delivery and litter size were significantly high at $1,330{\mu}g/L$ DEHP water. The number of epididymal sperm was significantly increased by drinking of $1,330{\mu}g/L$ DEHP water. In addition, the number of follicles (primary, secondary, tertiary) were more many than control at $1,330{\mu}g/L$ DEHP water drunk mother. Though further studies are needed to identify what are the mechanism of DEHP in folliculogenesis and spermatogenesis. From this study we firstly report the effect of low-dose chronic administration of DEHP with drinking could change the ovarian follicle population size and spermatogenesis rate. Put together, those finding is different from previous high-dose effects and suggest the physiological role of DEHP in gonads and uterus.

산란계 육성기 계란급이가 초기 산란 특징에 미치는 영향

  • 김상호;장병귀;최철환;서옥석;이상진;류경선
    • 한국가금학회:학술대회논문집
    • /
    • 한국가금학회 2003년도 제20차 정기총회 및 학술발표회
    • /
    • pp.97-98
    • /
    • 2003
  • 육성기 제한급이가 육성기 발육특성 및 기초 산란형태에 미치는 영향을 규명하기 위하여 갈색 산란계 1,080수를 공시하여 24주간 사양시험을 실시하였다. C는 자유채식을 시켰으며, T1은 6∼12주령까지 대조구 70%, 18주령까지 75% 수준으로 급여하였고, T2는 12∼18주령까지 T1과 동일하게 급여하였다. 18주령 체중은 T1이 가장 낮게 나타났고 C와 T2는 비슷하게 나타났으나 20주령 체중은 처리간 모두 비슷하게 나타났다. 18주령까지 사료섭취량은 T1이 가장 적었으며 C가 가장 많았다. 초산일령은 C가 가장 빨랐지만 90% 산란일정은 T1이 가장 빠른 것으로 나타났다. 연란과 쌍란 발생률은 C가 가장 많았고 T1이 가장 적은 것으로 나타났다. 이상과 같은 결과에서 육성 초기 사료 제한급이는 육성기 사료섭취량과 산란초기 연란 및 쌍란 발생률을 감소시키며 급격한 산란증가를 유도하는 것으로 나타났다.

  • PDF

CPC (Compound Parabolic Collector) 내 이산화티탄을 이용한 비스페놀 A (Bisphenol A)의 분해에 관한 연구 (Study of Degradation of Bisphenol A with $TiO_2$ Powder in CPC System)

  • 황안나;임명희;박범국;김지형
    • 한국방재학회 논문집
    • /
    • 제11권1호
    • /
    • pp.107-112
    • /
    • 2011
  • 본 연구는 CPC 시스템 내에서 $Tio_2$ 슬러리와 UVA 광촉매 반응을 이용한 내분비계장애물질의 하나인 Bisphenol A(BPA)의 분해와 무기화에 대한 연구이다. 실험 영향인자로는 초기농도, 촉매량, UVA 램프 파워, 온도를 고려하였고, 초기농도는 5, 10, 20 mg/L, 촉매량은 0.1, 0.5, 1.0 g/L, UV 램프는 40, 80, 120 W, 온도는 10, 20, 30 로 조절하여 실험하였다. 초기농도 가 5 mg/L일 때 BPA는 반응시간 10분에서 80%이상이 분해되었고, 1시간 이후 10 mg/L에서는 97%, 20 mg/L에서는 49%가 분해되었다. $Tio_2$ 주입량이 0.1, 0.5 g/L일 때 BPA 분해는 비슷한 경향을 보였으며, 1시간 이후 약 70%가 분해되었으며, 1 g/L에서는 30분 이후에는 80%이상이 분해되었다. 이것은 촉매량이 증가할수록 오염물질과 반응하는 활성점이 증가하여, 광촉 매 반응 또한 증가하기 때문이라 판단된다. UV 램프가 120W일 때 반응시간 10분에서 BPA는 약 60% 이상 급격히 분해 되었다. 온도에 따른 분해정도를 알아보기 위해 온도를 조절하며 수행하였고, 온도에 따른 영향은 크지 않았다. 10 에서는 1시간 이후 46% 분해되었으며, 20에서 67%, 30에서는 69% 분해되었다.

A Prospective Study on the Value of Ultrasound Microflow Assessment to Distinguish Malignant from Benign Solid Breast Masses: Association between Ultrasound Parameters and Histologic Microvessel Densities

  • Ah Young Park;Myoungae Kwon;Ok Hee Woo;Kyu Ran Cho;Eun Kyung Park;Sang Hoon Cha;Sung Eun Song;Ju-Han Lee;JaeHyung Cha;Gil Soo Son;Bo Kyoung Seo
    • Korean Journal of Radiology
    • /
    • 제20권5호
    • /
    • pp.759-772
    • /
    • 2019
  • Objective: To investigate the value of ultrasound (US) microflow assessment in distinguishing malignant from benign solid breast masses as well as the association between US parameters and histologic microvessel density (MVD). Materials and Methods: Ninety-eight breast masses (57 benign and 41 malignant) were examined using Superb Microvascular Imaging (SMI) and contrast-enhanced US (CEUS) before biopsy. Two radiologists evaluated the quantitative and qualitative vascular parameters on SMI (vascular index, morphology, distribution, and penetration) and CEUS (time-intensity curve analysis and enhancement characteristics). US parameters were compared between benign and malignant masses and the diagnostic performance was compared between SMI and CEUS. Subgroup analysis was performed according to lesion size. The effect of vascular parameters on downgrading Breast Imaging Reporting and Data System (BI-RADS) category 4A masses was evaluated. The association between histologic MVD and US parameters was analyzed. Results: Malignant masses were associated with a higher vascular index (15.1 ± 7.3 vs. 5.9 ± 5.6), complex vessel morphology (82.9% vs. 42.1%), central vascularity (95.1% vs. 59.6%), penetrating vessels (80.5% vs. 31.6%) on SMI (all, p < 0.001), as well as higher peak intensity (37.1 ± 25.7 vs. 17.0 ± 15.8, p < 0.001), slope (10.6 ± 11.2 vs. 3.9 ± 4.2, p = 0.001), area (1035.7 ± 726.9 vs. 458.2 ± 410.2, p < 0.001), hyperenhancement (95.1% vs. 70.2%, p = 0.005), centripetal enhancement (70.7% vs. 45.6%, p = 0.023), penetrating vessels (65.9% vs. 22.8%, p < 0.001), and perfusion defects (31.7% vs. 3.5%, p < 0.001) on CEUS (p ≤ 0.023). The areas under the receiver operating characteristic curve (AUCs) of SMI and CEUS were 0.853 and 0.841, respectively (p = 0.803). In 19 masses measuring < 10 mm, central vascularity on SMI was associated with malignancy (100% vs. 38.5%, p = 0.018). Considering all benign SMI parameters on the BI-RADS assessment, unnecessary biopsies could be avoided in 12 category 4A masses with improved AUCs (0.500 vs. 0.605, p < 0.001). US vascular parameters associated with malignancy showed higher MVD (p ≤ 0.016). MVD was higher in malignant masses than in benign masses, and malignant masses negative for estrogen receptor or positive for Ki67 had higher MVD (p < 0.05). Conclusion: US microflow assessment using SMI and CEUS is valuable in distinguishing malignant from benign solid breast masses, and US vascular parameters are associated with histologic MVD.

한방공중보건서비스 만족도와 개선방안 (A Study on Satisfaction level with Herbal Public Health Services and its Improvement Plans)

  • 이재원;구진숙;서부일
    • 한국한의학연구원논문집
    • /
    • 제18권2호
    • /
    • pp.65-89
    • /
    • 2012
  • Objective : In order to investigate and improve public Korean medical health service satisfaction level, this study was designed. Method : A questionnaire has been conducted on 212 patients who received treatments at six public health centers in the northern part of Gyeongbuk during 15 days between Sep. 24 and Oct. 8, 2011. Result : 1. An Investigation on the usage of herbal clinics in public health centers reveals that 63.7% have received three times or more medical treatments previously and 61.8% have had their illness treated at other medical institutions. In regard to illness 32.1% have had arthritis or muscle aches. 50.9% have taken insurance medication after having had treatments at the public health centers. 66% have assessed acupuncture and moxa cautery the most satisfying. 2. To a question regarding whether herbal health treatment costs higher than that of physician's, the highest response at 31.6% is 'No'. And to a question regarding whether herbal medicines administered at public health centers have more side effects than that of physician's, the highest response at 39.6% is 'No'. 3. To a question regarding whether herbal treatment of public health centers has little effect against acute disease, 48.1% of responses are 'Fair'. To a question regarding whether herbal treatments, when compared with physician's treatments, boost better recovery of patients, 48.1% of responses are 'Fair'. To a question regarding whether herbal medicine is unscientific, when compared with that of western medicine, 38.2% of responses are 'Fair', To a question regarding whether herbal medicine has faster effect on disease than western medicine, 41.0% of responses are 'Fair'. To a question regarding whether herbal medicine is more effective on disease prevention and promotion of health than disease treatment, 38.2% of responses are 'Fair'. And to a question regarding whether the lack of various types of physical therapy devices in herbal medicine, when compared with western medicine causes inconvenience in herbal treatment, 42.0% of responses are 'Fair'. Those responses take up highest portion at each questionnaire. 4. A comparative study between herbal treatments and physician's treatments has also been conducted. To questions regarding which one of the two considering types of disease is the better, responses are the latter accounted for 43.9% against 'Cancer', the latter accounted for 45.3% against 'Endocrine disorders', the former accounted for 30.7% against 'Psychiatric disorders', the latter accounted for 38.2% gainst 'Otolaryngological(ENT) disease', the former accounted for 47.6% against 'Post traumatic stress disorder', and the former accounted for 52.4% against 'Muscle-skeletal disease'. 5. An investigation on frequency of patients' visits via (p<0.05) of subjects show a statistically significant difference. 6. First, an investigation on frequency of reasons of medical treatments reveal that age, occupation, monthly income, and insurance type (p<0.05) of subjects show a statistically significant difference. Secondly, an investigation on frequency of subjects taking insurance medicines after herbal health treatments reveal that monthly income (p<0.05) of subject shows a statistically significant difference. 7. First, an investigation on frequency of a claim that herbal treatments of public health center does not have great effect on acute disease reveals that age, education, and insurance type (p<0.05) of subjects show a statistically significant difference. Secondly, an investigation on frequency of analysis that herbal treatments has faster effect on disease compared with western treatments reveals that education level, religion, monthly income, and insurance type (p<0.05) of subjects show a statistically significant difference. 8. When herbal clinics of public health centers and general herbal medicine institutions are compared, a survey on additional treatments that herbal clinics need the most reveals that education level, monthly income, and insurance type (p<0.05) of subjects show a statistically significant difference. Secondly, an investigation on frequency of subjects who want various forms of herbal medicines reveals that occupation and insurance type (p<0.05) of subjects show a statistically significant difference. Conclusion : In order to improve efficiency of treatments and enhance patient's satisfaction level, this study suggests measures such as providing a differentiated acupuncture treatments as a whole, streamlining an reception procedure, adopting more elaborated computer system for a patient to get proper medical attention, standardizing a treatment duration in order for a maximum result, keeping regular office hours, and optimizing a consultation time for a patient.

단삼보혈탕(丹蔘補血湯)이 Stress로 유발(誘發)된 백단삼보혈탕(白丹蔘補血湯)이 Stress로 유발(誘發)된 백서(白鼠) 위장관(胃腸管)의 조직손상(組織損傷)에 미치는 영향(影響) (Effects of Dansambohyultang on the Gastrointestinal Mucosa of Rats Stressed by Heating, Immobilization and Starvation)

  • 류봉하;박동원;류기원;공현식
    • 대한한방내과학회지
    • /
    • 제21권1호
    • /
    • pp.74-86
    • /
    • 2000
  • Objectives : This is the experimental paper to study the curative and preventive effects of Dansambohyultang, Methods : Oriental herb medicine for gastro-intestinal disease caused by stress, on the rats put under the stress through starvation, heating and immoblization, the author used four different group; the normal group, which was not put under stress and well fed, and the control group, to which the drug was not administered and put under the stress through starvation, heating and immoblization, the Sample I, to which the drug was administered before they were put under stress, the Sample lI, to which the drug was administered after they were put under stress. Results : When a Masson's trichrome stain method was applied to the control group, a small size of ulcer was found in the fundus and the pylorus, and atrophy was observed in the neck region of mucous membrane. When the drug was administered to the Sample I and the Sample II, the former recovered from the ulcer and atrophy to almost normal and showed better results than the latter. When a Masson's trichrome stain method was applied to the control group, atrophy of mucous membrane was found all over the intestines. When the drug was administered to the Sample I and the Sample ll, the curative and recovered effects was seen in both, but the former showed better results than the latter. After application of Mayer's hematoxylin stain method, the observation of numerical changes of goblet cells in the small intestines showed the most significant decrease in the control group. In the Sample I, the number of the cells in the duodenum, the jejunum and the ileum returned to an almost normal level. In the Sample II, a slight increase was observed only in the ileum. After application of Mayer's hematoxylin stain method, the observation of numerical changes of goblet cell in the large intestines showed a significant decreased in the control group. Both the Sample I and the Sample II showed an increase in the number of goblet cells in comparison with the control group. When a serotonin-immunoreaction test was applied, the control group showed a general decrease in the number of gastro-entero-endocrine cells, The Sample I showed the effect in all over gastro.intestinal tract as compared with control group and the Sample II showed the effect in all over gastro-intestinal tract except the duodenum and the former showed better results than the latter. Conclusion : According to the above results, the regions which are most sensitive to stress were observed to the ileum and the colon. It was concluded that Dansambohyultang has a remedical value particularly on the abnormalities caused by stress in all over gastro-intestinal tract and it was found to be more effective in the Sample I than in the Sample ll. Judging from the fact that the Sample I showed better results than the Sample ll, Dansambohyultang can be said to have a preventive effect more than a curative effect on gastro-intestinal tract disease.

  • PDF

Streptozotocin 유발 당뇨쥐에서 팽화가공 처리한 홍삼의 항당뇨 효과 (Antidiabetic Effect of Korean Red Ginseng by Puffing Process in Streptozotocin-Induced Diabetic Rats)

  • 김신희;강주섭;이상준;정영진
    • 한국식품영양과학회지
    • /
    • 제37권6호
    • /
    • pp.701-707
    • /
    • 2008
  • 본 실험에서는 STZ로 당뇨를 유발시킨 흰쥐에 홍삼과 팽화홍삼의 항당뇨 효능에 대한 생리활성을 규명하고자 홍삼을 7주간 경구투여 후 체중, 혈당, 혈청 인슐린 및 아밀라아제, 지질관련 지수, OGTT, DNA의 산화적 손상정도 분석 및 췌장의 조직병리학적 변화를 관찰하였다. 체중증가는 실험 7주 후에 DM군과 비교 시 RG군에서 6.67배, PG군에서 5.25배 증가하였으나 DM군과 유의적인 차이는 없었다. 공복혈당은 DM군에 비해 RG군에서 11.54%, PG군에서 20.22%의 감소를 보였다. 구강내당능 검사결과 공복혈당, 포도당 투여 2시간 후 혈당은 DM군과 통계적 유의성은 없었다. 혈청 인슐린 농도는 PG군에서 가장 높게 나타났고, 혈청 아밀라아제 농도의 경우 RG군에서 높았으나 NC군보다는 낮게 나타났다. 혈청 총 콜레스테롤은 NC군을 제외한 모든 실험군 간에 유의적인 차이를 보이지 않았으나 혈청 중성지방의 경우 PG군에서 현저한 감소를 보였다(p<0.05). HDL-C는 NC군에 비해 당뇨유발군 모두에서 높게 나타났다. DNA 손상정도를 알아보기 위한 comet 분석에서는 PG군의 TL 및 TM은 NC군에서와 유사한 수준을 보였다. 췌장조직의 병리학적 관찰결과, 당뇨유발군 중 DM군의 췌장조직의 exocrine acinal cell 및 췌도세포에서는 focal 또는 multifocal cytoplasmic vacuolation과 췌장실질의 괴사 및 출혈성 병변이 관찰되었다. 이상의 결과로서 팽화홍삼의 투여가 홍삼에 비해 항당뇨 효과가 더 큰 경향을 보였으나 보다 확실한 결과를 위해 8주 이상의 홍삼 장기투여에 의한 항당뇨 효과 확인이 필요할 것으로 사료된다.

고려인삼의 주요 효능과 그 임상적 응용 (Clinical Applications and Efficacy of Korean Ginseng)

  • 남기열
    • Journal of Ginseng Research
    • /
    • 제26권3호
    • /
    • pp.111-131
    • /
    • 2002
  • 본 총설은 1980년대부터 최근까지 국내외 학술잡지나 심포지움 등에 발표된 인삼의 주요 임상효능 연구결과를 요약 고찰하고, 그 임상 적응증과 안전성 등에 대한 검토를 통해 금후 인삼의 임상적 활용성 제고와 인삼의 진정한 약용가치 평가를 위한 임상연구의 발전에 도움을 주고자 하였다. 당뇨병을 비롯한 동맥경화성 질환, 고혈압, 악성질환, 성기능 장애 등의 만성질환에 대한 그 동안의 연구결과는 인삼의 치료효과보다는 예방 및 회복제로서의 효용성을 보여 주었다. 특히 이들 질환의 각종 자각적 장해증상과 장기 약물치료의 부작용으로 인한 QOL의 악화에 에 대한 개선효과가 관찰되었다. 그러나 인삼의 효과는 일반적으로 mild 하여 일차적 치료보다는 관행적 약물요법과 병용할 때 보조요법제로서 또는 부작용을 보다 적게 하는 효과가 기대된다. 또한 주요 강장효능과 관련하여 작업수행능력에 미치는 임상연구 결과는 인삼복용이 각종 스트레스 상태하의 신체적 조건에 대한 적응능력을 개선시켜 육체적 정신적 기능저하를 회복시키는 효과를 보였다. 이러한 임상시험에서 얻어진 결과가 그대로 인삼의 적응증(indication)이라고 단정할 수는 없으며, 그 효능의 과학적 증거들에 대해서는 아직도 논란이 많고, 임상실험의 유효성 평가와 관련된 방법론적 문제점도 많이 지적되고 있다. 보다 확실한 적응증 제시를 위해서는 표준화된 인삼시료를 이용하여 보다 체계적인 시험설계에 의한 객관적 효능평가가 필요하다. 한편 인삼(제품)복용에 의한 부작용(adverse effects)의 발생 가능성에 대한 사례보고들도 대부분 인삼의 과량복용이나 품질관리 미흡에서 기인되는 것으로 여겨지고 있다. 최근 해외 시장에서 유통되는 인삼제품 품질검사에서 사포닌 성분의 불검출 또는 함량 미달과 유해성분의 오염가능성 등 부정적 견해들이 다수 보고되었다. 그러나 표준화된 인삼제품의 추천 복용량을 사용한 대부분의 임상실험에서는 거의 유의할만한 부작용은 인정되지 않았다. 금후 연구와 관련하여, 품질표준의 지표성분으로 간주되는 진세노사이드의 절대함량과 그 성분조성 차이에 따른 임상효과의 차별성이 있는지에 대한 검토와, 특히 최근 실험적으로 밝혀지고 있는 사포닌 성분의 장내 세균에 의한 생물전환체의 인체 실험을 통한 효과 검정이 필요하다. 나아가서는 적정 복용량의 설정과 이와 관련되는 생체내 동태 및 생체이용율(bioavilability)에 관한 정보가 거의 없으므로 이것도 금후 검토해야 할 과제로 사료된다. 인삼은 전통약물로서 오랜 역사성과 그동안의 연구결과에 의한 과학성을 가지고 있으므로 건강유지와 병의 예방 및 회복촉진을 위한 보조요법제 또는 기능성 식품으로써의 유용성이 있는 것으로 판단된다. 앞으로 인삼의 활용성 증대를 위해서는 보다 과학적인 임상평가에 의한 안전성 및 유효성 입증과 제품의 엄격한 품질관리의 필요성이 더욱 강조되어야 할 것이다.