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In recent years, propolis has attracted much attention as an useful substance in medicine and functional food, even if it is known as a natural remedy in folk medicine since ancient times. propolis was registered as natural food since 1995 on Korean Food Act by Korean Food and Drug Administration(KFDA). The present study demonstrated the optimization of isolation of crude propolis by ethanol, and tumoricidal effect of pro polis. The optimal concentration of ethanol to separate a high quantity of propolis was $60\%$. The cytotoxic effect of ethanol extracted propolis against various cancer cell lines including murine lymphoma (Sarcoma-180), murine T-lymphoma (YAC-1), human breast carcinoma (MCF-7), human gastric carcinoma (KATOIII) and human hepatocellular carcinoma (Hep3B) and human lung adenocarcinoma (A-549) was observed using SRB and MIT assay. In order to investigate the curative activity by oral administration of propolis on tumor, ICR mice was subcutaneously implanted Sarcoma 180. In 300mg/kg and 600mg/kg propolis administered group, development of implanted tumors was inhibited by $40.9\%\;and\;67.9\%$ at 16th day, respectively. In the same dose of propolis administered group, development of implanted tumors was inhibited more strongly with dose dependent manner. Therefore, these data suggested propolis may show tumoricidal effects. In conclusion, these results indicate that propolis, one of the few natural remedies, can be used as functional food with tumoricidal effects.
We investigated effects of recombinant human erythropoietin (rHuEPO) on body weight, organ weight, hematology, serum biochemistry, and histopathology in 6 male cynomolgus monkeys (Macaca fascicularis). Six monkeys, composed of treatment and control groups, were intravenously administered 3 times per week at doses of 0 and 2730 IU/ 0.1 ㎖/㎏ with rHuEPO for 4 weeks. rHuEPO treatment did not show any change in body weights for 4 weeks and caused an increase of organ weight in spleen, salivary gland, kidney, and liver. rHuEPO treatment increased significantly mean corpuscular hemoglobin concentration, reticulocyte, and red cell distribution width from day 3 of the study and red blood cells, hemoglobin, and hematocrit levels were increased significantly from day 7 or 10 up to day 28. For an increase in red cell distribution width, it was found to a large extent on day 7, day 10, and day 14, while was found to a small extent on day 21 and day 28. It increased platelet distribution width on day 10, day 14, day 21, and day 28. Histopathological examination showed that rHuEPO treatment caused an extramedullary hemopoiesis in spleen and bone marrow hyperplasia in sternum and femur. The results indicated that rHuEPO treatment caused an increase in platelet-and RBC-related parameters, extramedullary hemopoiesis of spleen, and bone marrow hyperplasia of sternum and femur. The present study will be valuable in the proper interpretation and validation of general toxicology studies for biogeneric drugs including rHuEPO in cynomolgus monkeys.
김수남(Soo Nam Kim), 이용순(Yong Chun Li), 서홍덕(Hong De Xu), 이동근(Dong Geun Yi), 김민섭(Min Seop Kim), 이성표(Sung Pyo Lee), 이권택(Kwon-Taek Yi), 이재경(Jae Kyoung Lee), 김재수(Jae Soo Kim), 권명상(Myung-Sang Kwon), 장판식(Pahn-Shick Chan) 韓國食品科學會 2008 한국식품과학회지 Vol.40 No.3
본 논문에서는 1년간의 임상연구 결과 폐경기 증상 개선효과와 골밀도 개선 효과가 관찰된 에스트로몬의 주요 성분인 복합 식물추출물인 FGF271의 식물성에스트로겐 효과를 검증하기 위해 난소를 절제한 rat 동물모델에서 FGF271과 에스트로몬을 비교 실험하였다. 시험군과 OVX 대조군간의 체중 자궁 신장 및 간 무게 변화는 없는 것으로 나타나 FGF271이나 에스트로몬이 이들에 영향을 미치지 않았고 FGF271을 투여한 군에서 혈청 osteocalcin 농도가 통계적으로 유의한 개선효과를 보였다(p<0.05). 한편 FGF271과 에스트로몬 투여군에서 대퇴부 골밀도(Femoral Bone Mineral Density FBMD)는 투여용량 73.5 180 440 ㎎/㎏/day 모두에서 유의하게 증가하였고(p<0.05) FGF271 투여군의 상대적 FBMD는 용량 의존적인 증가 경향을 나타내었다. FGF271 기준으로 동량 투여시(73.5 ㎎/㎏/day; G4와 G8 180 ㎎/㎏/day; G5와 G9) 비교군 간에는 유의한 차이가 나타나지 않았다. 이로써 에스트로몬 투여군의 FBMD 증가가 에스트로몬의 주요성분인 백수오등 복합추출물인 FGF271만에 의해서 증가하였다고 판단할 수 있다. 이상의 결과 임상시험에서 폐경기 증후군에 효능이 있는 것으로 확인된 에스트로몬의 식물성에스트로겐 효과는 Cynanchum wilfordii(백수오) Phlomis umbrosa(속단) Angelica gigas(당귀) 복합추출물로 구성된 FGF271에 기인하는 것으로 판단되었다. This study examined the combined plant extracts (FGF271) of Estromon in ovariectomized (OVX) rats to determine whether Estromon's significant clinical improvement effects on menopausal symptoms are predominantly due to the phytoestrogenic action of the combined extracts. The results showed that all three FGF271-treated groups had significantly improved serum osteocalcin levels as compared to the control group (p<0.05). In addition all FGF271- and Estromon-treated groups had increases in femoral bone mineral density (FBMD) (p<0.05) and the increase in the FGF271 group was dose-dependent. A pairwise comparison of the FGF271- and Estromon-treated groups receiving the same dosage of FGF271 indicated that there was no significant difference between the groups. Therefore the FBMD increases that occurred in the Estromon groups were solely attributable to the phytoestrogenic effects of FGF271. It was conclude that the phytoestrogenic effects of Estromon as shown in clinical studies are predominantly caused by FGF271 the mixed extracts of Cynanchum wilfordii Phlomis umbrosa and Angelica gigas.
윤석주(Seokjoo Yoon), 황지윤(Ji-Yoon Hwang), 임정선(Jung-Sun Lim), 정선영(Sun-Young Jeong), 김용범(Yong-Bum Kim), 김달현(Dal-Hyun Kim), 권명상(Myung-Sang Kwon), 한상섭(Sang-Seop Han), 김충용(Choong-Yong Kim) 한국독성학회 2005 Toxicological Research Vol.21 No.3
We investigated effects of recombinant human erythropoietin (rHuEPO) on profiles of mRNA transcripts in 6 male cynomolgus (M. fascicularis) monkey's spleen for 4 weeks. Six monkeys, composed of control and treatment group (Control : M1, M2, M3; Treatment : M4, M5, M6) were intravenously administered 3 times per week without or with a dose of rHuEPO 2730 IU/0.1 ㎖/㎏. After 4 weeks rHuEPO treatment, spleen was removed for RNA isolation. Splenic gene expression was assessed using Affymetrix U133A 2.0 arrays containing 18,400 transcripts and variants, including 14,500 well-characterized human genes. Gene expression pattern was very different between individuals even in same treatment. In rHuEPO treated groups showed number of genes were up-or downregulated (M4: 79; M5: 48; M6: 73 genes). Six genes (epidermal growth factor receptor, calgranulin A, estrogen receptor binding site associated antigen, matrix metalloproteinase 19, zinc finger and BTB domain containing 16, progestin and adipoQ receptor) were commonly expressed in rHuEPO treated group. The different individual response could be major considering factor in monkey experiment. Further study is needed to clarify the different individual response to rHuEPO in molecular level. This study will be valuable in the fundamental understanding and validation of molecular toxicology for biogeneric drugs including rHuEPO in cynomolgus monkey.
To identify immune response of leukocytes in peripheral blood of cattle vaccinated with an attenuated live Akabane virus vaccine, leukocytes were reacted with monoclo-nal antibodies which are specific to bovine lymphocyte surface antigens and assayed by the flow cytometry. Serum neutralizing(SN) test was used to measure antibody titers after vaccination. SN antibody was appeared to 7 days post-vaccination(PV) and 2-8 antibody titers were observed in 14 days PV. Proportion of CD8-MHCclassⅡ+ expressing cells were rapidly increased at 3 days PV. CD8+MHCclassⅡ- cells were increased at 7 days PV. CD4+CD8-, WC+CD4-, CD4+CD8+, WC1-CD4+, WC1-CD8+, and CD4-CD8+ cells were highly increased at 3, 3, 7, 7, 14, 14 days PV, respectively.
To investigate the anti-diabetic effects of water-extracted propolis (WEP) in streptozotocin (STZ)-induced diabetic rats, male Sprague-Dawley (SD) rats were induced diabetes mellitus by the STZ injection (45㎎/㎏ b.w.) and were divided into 3 groups and subjected to one of the following treatments. Negative control group received basal diets and two of STZ treated group supplied with 150 or 300㎎/㎏-WEP (WEP groups) orally for 4 weeks, respectively. Diabetic rats group was showed the lower weight compared to the normal rats. Food diet and drinking water supply in STZ treated group was higher than in normal or WEP groups. The plasma glucose levels of the WEP-treated groups were lower than STZ-control group. In macrophage cell culture, cytokines (TNF-α, IL-1β, IFN-γ) levels in WEP-treated groups was decreased compared with STZ treated group. Spleen cell proliferation by treatment LPS was significantly increased. Immunostaining of insulin containing immune cells at pancreas tissue in WEP-treated group were significantly increased compared with STZ group. These results suggests that WEP may contributes an anti-diabetic action by inhibition of diabetic inducing substances such as IL-1β, TNF-α, IFN-γ or by induction of insulin regulating glucose.