Antidiabetic Activity of Angelan Isolated from Angelica gigas Nakai

김환묵,강종순,박송규,이기호,김연진,홍진태,김영수,김지윤,한상배 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.11

Angelan isolated from Angelica gigas Nakai inhibits tumor growth and metastasis by enhancing immune functions of macrophages, dendritic cells, and B cells. Here, we report that angelan can inhibit autoimmunity in non-obese diabetic (NOD) mice. Although 80% of the NOD mice had developed diabetes by 24 weeks of age, none of the angelan-treated NOD mice developed diabetes. The mean glucose levels were 118 mg/dl in angelan-treated mice and 506 mg/dl in control NOD mice. Histological examination of the pancreatic islets revealed that most of the islets isolated from angelan-treated mice were less infiltrated with lymphocytes compared with those of control mice. Spleen cells from diabetic NOD mice could adaptively transfer diabetes into NOD.scid mice, but those from angelan-treated NOD mice did not, suggesting that angelan caused the spleen cells to lose the ability to destroy β cells. However, angelan did not affect cytokine production of spleen cells. These results suggest that angelan has dual immunomodulatory functions, i.e., immunostimulation in tumor-bearing mice and immunosuppression in autoimmune diabetic mice.

Integration of Human Cells into Pharmacological and Toxicological Studies

김환묵 충북대학교 약품자원개발연구소 1994 약학논문집 Vol.9 No.-

우리 고장의 자랑 : 연구실천하는 행정 - 충청북도 괴산군 이동정 (里洞政) 관리를 잘하고 있는 사례 -

김환묵 대한지방행정공제회 1971 地方行政 Vol.20 No.208

Inhibition of Human Ovarian Tumor Growth by Cytokine-induced Killer Cells

김환묵,강종순,임재승,박성규,이기호,윤여대,이창우,이기훈,한균희,양규환,김연진,김영수,한상배 대한약학회 2007 Archives of Pharmacal Research Vol.30 No.11

Despite the recent improvement in the treatment of ovarian cancer, this disease is still leading cause of cancer death in women. In this study, the anti-tumor activity of cytokine-induced killer (CIK) cells against human ovarian cancer was evaluated in vitro and in vivo. Although CD3+CD56+ cells were rare in fresh human peripheral blood mononuclear cells, they could expand more than 1,000-fold on day 14 in the presence of anti-CD3 antibody plus IL-2. At an effector-target cell ratio of 30:1, CIK cells destroyed 45% of SK-OV-3 human ovarian cancer cells, which was determined by the 51Cr-release assay. In addition, CIK cells at a dose of 23 million cells per mouse inhibited 73% of SK-OV-3 tumor growth in nude mouse xenograft assay. This study suggests that CIK cells may be used as an adoptive immunotherapy for patients with ovarian cancer.

신령버섯 (Agaricus blazei) 으로부터 면역증강활성 다당류의 분리 및 화학적 특성

김환묵,유익동,조수묵,박정식,김광포 한국균학회 1999 韓國菌學會誌 Vol.27 No.2

Water-soluble polysaccharides from the fruiting bodies of Agaricus blazei Murill were extracted with 0.9% sodium chloride and hot water, successively. The purified polysaccharides showed a potent immunostimulating activity. Eight major polysaccharides, which were named from AG-1 to AG-8, were fractionated and purified by ethanol precipitation, ion exchange chromatography on DEAE-cellulose and gel filtration on Toyopearl HW 65F. These polysaccharides were identified to be homogeneous by analysis of HPLC. Three major active polysaccharides (AG-2, -3, and -6) showed relatively strong immunostimulating activity. AG-2 and -3 were composed of glucose, galactose and mannose in the molar ratios of 74.0:15.3:10.7 and 63.6:17.6:12.7, respectively. AG-6 was composed of glucose and ribose in the molar ratios of 81.4:12.6.

CD18 단일클론항체와 Superoxide Dismutase을 이용한 재관류 손상의 예방

강낙헌,손경동,한기택,임풍,김환묵 大韓成形外科學會 1998 Archives of Plastic Surgery Vol.25 No.1

Prolonged ischemia results in cellular necrosis and only prompt restoration of blood flow will prevent this type of injury. However, reperfusion itself can cause significant injury of previously ischemic tissue, i.e. "reperfusion injury'. This is an issue of concern in many areas of reconstructive surgery including free tissue transfer and replantation. Many factors have been implicated in the cause of reperfusion injury. Oxygen free radicals have enjoyed increasing popularity recently, but leukocytes had been thought to have a role only in the healing process that follows ischemic injury. Current studies in myocardium, liver and intestine have shown a dramatic increase in tissue leukocytes after ischemia-reperfusion and evidence implicating leukocytes in pathogenesis of ischemia-reperfusion injury has come from studies demonstrating significant injury reduction by depletion of circulating neutrophils. Therefore, increased neutrophil adhesiveness is a critical early step in the sequence of events leading to neutrophil-mediated injury. The purpose of this study is to evaluate the effect of CDl8 monoclonal antibody(CDl8 mAb), blocking antibody of neutrophil adherence, and superoxide dismutase (SOD), free radical scavenger, on reperfusion injury in rat epigastric island skin flap. The epigastric pedicle was occluded for six hours with ambient temperature at 22±1℃. The epigastric nerve was carefully dissected out and left intact to minimize autocannibalization. The flaps were sutured back down to their beds over interposed silicone sheets to prevent plasmatic imbibition. Fifteen minutes before reperfusion, the flaps were perfused with saline, CDl8 mAb(1 mg/kg), SOD(20,000 unit/kg) or CDl8 mAh/SOD(1 mg/kg + 20,000unit/kg). Percentage of flap survival was assessed by computerized planimetry on the seventh day. Tissue biopsies for myeloperoxidase(MPO) and malonyldialdehyde (MDA) were obtained at 24 hours after reperfusion. The results were as follows. 1. Percentage of flap survival was significantly increased in CDl8 mAb/SOD, CDl8 mAb and SOD groups in order, compared to the control(P < 0.05). Percentage of flap survival was significantly increased in CDl8 mAb group as compared with SOD group(p < 0.05). Percentage of flap survival significantly increased in CDl8 mAb/SOD group as compared with CDl8 mAb and SOD groups(p < 0.05) 2. MPO activity was significantly decreased in CDl8 mAb/SOD, CDl8 mAb and SOD groups(p < 0.01). MPO activity was significantly decreased in CDl8 mAb group as compared with SOD group. (p < 0.01). 3. MDA content was significantly decreased in CDl8 mAb/SOD, CDl8 mAb and SOD groups (p < 0.01), but the difference between CDl8 mAb and SOD groups was not significant. From those above results, we get to the conclusion that blocking neutrophil adherence and/or aggregation with monoclonal antibodies to CDl8 as compared with radical scavenger significantly ameliorates reperfusion injury. It is suggested that combination of modalities with antiadhesion therapy and radical scavenger may have a synergistic effect of improving flap survival and may be the optimal prevention of ischemiareperfusion injury.

실리콘 겔에 활성화된 복강 대식세포의 interleukin-6 및 tumor necrosis factor-α에 의한 섬유모세포 중식 자극

김환묵,한상배,이백권,이종원,한기택,천지훈 大韓成形外科學會 1998 Archives of Plastic Surgery Vol.25 No.5

Silicone gel breast implants may induce local(fibrous capsular contracture) or systemic(rheumatoid arthritis, systemic sclerosis, etc) complications. The exact mechanism of fibrous capsular contracture has not been fully understood. In the present study, we tried to find out the effect of silicone gel on the fibroblast proliferation which has been known as a major contributing factor in fibrous capsular contracture formation. In vitro, activated macrophages are known to secrete monokines which affect fibroblast proliferation and collagen synthesis. And tumour necrosis factor-α(TNF-α) and interleukin-6(IL-6), which were released by macrophages, were reported as potent stimulator of fibroblast proliferation. The goal of this study is to investigate the role of macrophages and tumour necrosis factor-αor interleukin-6 in the interaction of fibroblasts and silicone gel. We designed four groups, two experimental and two control, using Institute for Cancer Research(ICR) mouse peritioneal macrophage and silicone gel. For the preparation of the conditioned medium of macrophages, peritoneal macrophages were prepared and cultured for 24 hours on the silicone gel-coated and naked (not coated) surface [silicone gel-macrophage conditioned medium(SCM; experimental group) and normal polystyrene-macrophage conditioned medium(NCM; control group) respectively]. To correct the effect of 10% fetal bovine serum which was included in Rapid Prototyping and Manufacturing Institute (RPMI) 1640 medium and draw the effect only by macrophages, the RPMI 1640 medium with 10% fetal bovine serum was cultured by the same method on the silicone gel-coated and naked surface (silicone gel-macrophage free conditioned medium; SFM and normal polystyrene-macrophage free conditioned medium; NFM respectively). Each conditioned medium was added onto NIH 3T3 fibroblasts culture at a final 25% concentration of total culture medium and followed by the cultivation for 24 hours. For antibody neutralizing experiments, each conditioned medium was preincubated with polyclonal rabbit anti-mouse TNF-α antibody or polyclonal rat anti-mouse IL-6 antibody for 1 hour and then, conditioned medium with antibody was added to the culture medium of NIH 3T3 fibroblasts by the same method. After 24 hours cultivation, total number of viable fibroblast(cell growth), DNA synthesis and collagen synthesis of fibroblasts with each medium were measured by sulforhodamine B(SRB) assay, 3H-thymidine and 3H-proline incorporation respectively. The results were as follows: 1. In the experiment about the effect of the conditioned medium on the fibroblast activity, the experimental group(SCM), compared with the control group(NCM), showed a significant increase of the cell growth (p<0.01), a significant decrease of DNA synthesis(p<0.001), but no significant difference in the collagen synthesis. 2. In the experiment about the effect of polyclonal rabbit anti-mouse TNF-α antibody on the fibroblast activity, after the addition of antibody the experimental group, compared with the control group, showed a significant decrease of the cell growth(p<0.001), a significant increase of DNA synthesis(p<0.01), but no significant difference in the collagen syn thesis. 3. In the experiment about the effect of polyclonal rat anti-mouse IL-6 antibody on the fibroblast activity, after the addition of antibody the experimental group, compared with the control group, showed a significant decrease of the cell growth(p<0.001), a significant increase of DNA synthesis(p<0.0001), but no significant difference in the collagen synthesis. In conclusion, culture supernatants (conditioned medium) of peritoneal macrophages, activated by silicone gel, stimulate the NIH 3T3 fibroblast proliferation. TNF-α and IL-6, products of macrophage, are involved in the stimulation of NIH 3T3 fibroblast proliferation in an in vitro condition.

Applications of Human Cells to In Vitro Pharmacological and Toxicological Evaluations of Chemicals

Kim, Hwan Mook 충남대학교 약학대학 의약품개발연구소 1993 藥學論文集 Vol.9 No.-

Synthesis and Cytotoxic Activities of C-benzylated Flavonoids

최윤정,김환묵,김희두 대한약학회 2009 Archives of Pharmacal Research Vol.32 No.1

Some C-benzylated flavonoids based on gericudranin A were synthesized and evaluated their cytotoxic activities for the elucidation of structure-activity relationship. 2,4,6-Trihydroxyacetophenone was converted to target molecules in 6~7 steps via sequential protection, aldol condensation, cyclization, regioselective C-benzylation, and deprotection. The cellular growth inhibition of the synthetic C-benzylated flavonoids was investigated against sixteen human cancer cell lines. Among these compounds, 5b showed the most potent cytotoxicities against several cell lines, especially as potent as adriamycin against SNB19 cell lines with an IC50 value of 0.7 μM.

유전자변형 생물체의 위해성평가

김형진,김환묵 한국독성학회 2003 Toxicological Research Vol.19 No.1

New breeding method by genetic engineering is expected as a key technology to solve food shortage due to the growing world population in the year 2000s. Many genetically modified organisms (GMOs) were aleady developed and the commercial cultivation had started. The first GMO, Flavr Savr tomato, which rotted at a much slower pace than ordinary ones, was developed in US in 1994. Since then, over then 70 different agricultual products including com, cotton, soybean, papaya, potato, and squash made with genetically modified plants are reportedly on sale worldwide. Supporters favor the GMOs because they have greater yields, longer shelf lives and stronger resistance to disease and insects. On the other hand, opponents say that the supporters ignore a potential danger that they may damage the environment as well as human beings. To assure the save development and use of GMOs as food and other biotech products, the possible risks on biological environment and human health should be throughly examined and regulated by developerf and government. Because the biosafety problem is a global, environmental, and tade issue, a new international treaty is under development. The Cartagena Protocol on Biosafety was adopted at the 1st Extraordinary Conference of Parties of the Convention on Biological Diversity which was held at Montreal, Canada, Jan 29th, 2000. The adoption of the Protocol is seen as a breakthrough in that it is based on the "Precautionary Principle" despite scientific uncertainties surrounding potential risks that GMOs may inflict on human health and the environment and that it has laid the ground fror introduction of specific steps to handle international trading of GMOs. In this paper, the authors would like to introduce the current status and perspective of environmental and human risk assessment of GMOs.