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연구논문 : 잔나비걸상버섯(Ganoderma applanatum) 균사체의 db/db Mice 및 인체에서의 항당뇨 효능연구
김갑호 ( Kap Ho Kim ),손달훈 ( Dal Hoon Son ),이준석 ( Joon Seok Lee ),이정운 ( Jeong Woon Lee ),김학수 ( Hak Soo Kim ),이재현 ( Jae Hyen Lee ),이문철 ( Moon Cheol Lee ),김남식 ( Nam Sik Kim ),송시환 ( Si Whan Song ) 한국식품영양학회 2013 韓國食品營養學會誌 Vol.26 No.3
Anti-diabetic activities of cultured mycelia from Ganoderma applanatum are being evaluated in this study. The OGTT and 4-weeks of repeated oral efficacy tests are conducted in mice at the doses of 0 (vehicle treatment), 25, 75 and 225 ㎎/㎏/day, respectively. In human study, the test article was administered orally every day for 8-week at a dose of 1,500 ㎎/㎏, tid and placebo group. The blood glucose levels (BGL) at 0.5 hour after treatment are significant decreased in all treatment groups of OGTT test. In the 4-week test, BGL of 75 and 225 ㎎/㎏/day group is continuously decreased during all treatment periods and the BGL of 25 ㎎/㎏/day group show decreasing trends at the final week, the pancreas weight of all treatment groups are being increased, and the Langerhans-islet numbers were increased at all treatment groups with a dose-response manner. There are no test article-related abnormal signs and the fasted blood glucose (FBG), postprandial blood glucose (PPG) and HbA1c are decreased significantly after 8-week treatments. These results that the cultured mycelia from Ganoderma applanatum could decrease BGL by protecting the degeneration of Langerhans islets.
새로운 백금착물 항암제 SKI 2053R 의 토끼 최기형성시험
김종춘(Jong Choon Kim),김갑호(Kap Ho Kim),박종일(Jong Il Park),김형진(Hyoung Chin Kim),정문구(Moon Koo Chung) 한국응용약물학회 1999 Biomolecules & Therapeutics(구 응용약물학회지) Vol.7 No.3
SKI 2053R, cis-Malonato[(4R,5R)-4,5-bis(aminomethyl)-2-isopropyl-1,3-dioxolane]platinum(II), is a newly developed antitumor platinum complex derived from cisplatin. Preclinical studies suggest that it may have greater antitumor activity and lower toxicity than cisplatin. Effects of test agent on general toxicity of does and embryonic development of F1 fetuses were investigated in rabbits. Sixty eight New Zealand white rabbits were distributed among three treated groups and a control group. SKI 2053R was administered intravenously to pregnant rabbits from days 6 to 18 of gestation at dose levels of 0, 0.67, 2.0, or 6.0 ㎎/㎏/day. The pregnant does were subjected to the caesarean section on day 28 of gestation. No treatment-related changes in clinical signs, body weight, food consumption, and necropsy findings were observed in all groups. F1 fetuses showed no changes related to the treatment of SKI 2053R, except that an increase in the incidence of skeletal variations were observed at 6.0 ㎎/㎏. There were no signs of maternal toxicity or embryotoxicity at 0.67 and 2.0 ㎎/㎏. The results show that the administration of 6.0 ㎎/㎏ SKI 2053R induces skeletal variations in fetuses and that the no observed adverse effect levels(NOAELs) of SKI 2053R are considered to be over 6.0 ㎎/㎏ for does and 2.0 ㎎/㎏ for F1 fetuses in rabbits.
기니픽을 이용한 BR92021 ( 정제 브이아이 장티푸스 백신 ) 의 항원성 평가
정태천(Tae Cheon Jeong),김갑호(Kap Ho Kim),배주현(Ju Hyun Bae),구희경(Hee Kyoung Gu),서정은(Jeong Eun Suh),박종일(Jong Il Park),차신우(Shin Woo Cha),임상민(Sang Min Lim),정한선(Hahn Sun Jung),김상린(Sang Lin Kim) 한국응용약물학회 1999 Biomolecules & Therapeutics(구 응용약물학회지) Vol.7 No.3
To study the antigenicity of BR92021(Vi polysaccharide typhoid vaccine), active systemic anaphylaxis and passive cutaneous anaphylaxis were tested in guinea pigs. The groups were as follows: group I(low dose, 30 ㎕/kg), group II(high dose, 300 ㎕/kg), group III(300 ㎕/kg plus complete Freund`s adjuvant), group IV(positive control, ovalbumin plus complete Freund`s adjuvant) and group V(saline-treated control). Male Hartley guinea pigs at 7 weeks of age were sensitized subcutaneously with the test article or saline three times per week for three weeks(i.e., total 9 times). For groups III and IV, animals were sensitized subcutaneously with either the test article or ovalbumin plus complete Freund`s adjuvant once per three week for 6 weeks(i.e., total 3 times). Twelve days after the last sensitization, the blood was collected from the sensitized animals for the passive cutaneous anaphylaxis test. In addition, the sensitized animals were subjected to the active systemic anaphylaxis test on fourteen days after the 1st sensitization by an intravenous challenge with either the test article or ovalbumin. In group I, mild(1/5) or moderate(4/5) symptoms of anaphylactic shock were observed. In group II, no sign(1/5), moderate(3/5) and severe(1/5) symptoms were observed. In group III, four animals of 5 revealed moderate signs and one of 5 showed no signs of anaphylactic shock. In group IV, all 5 animals showed severe signs of shock. In group V, one of 5 revealed moderate and four of 5 showed no signs. The necropsy findings related to the active systemic anaphylaxis were observed in most animals of groups I to V. In the passive cutaneous anaphylaxis test, the antiserum was diluted 10- to 5120- fold and was injected intradermally on the clipped back of recipient animals, followed by an intravenous challenge with either the test article or ovalbumin. No animals in groups I, II, III and V showed the positive reaction, whereas all animals in group IV, the positive control, showed the positive reaction at the dilution range of x1280 to x5120. Our results indicate that the test article, BR92021, may have weak antigenic potential in male guinea pigs.
Thioacetamide에 의한 BALB/c 마우스 간의 시간별 약물대사효소 억제 양상 : A Time-Course Study
이정운,고우석,김갑호,배연경,하현정,한상섭,천영진,정태천 영남대학교 약품개발연구소 2001 영남대학교 약품개발연구소 연구업적집 Vol.11 No.-
Thioacetamide is a potent hepatotoxicant which requires metabolic activation by cytochrome P450s (P450s) for toxicity. In the present study, the elevation kinetic of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities by thioacetamide treatment was investigated in male BALB/c mice. Inaddition, the inhibitory effects of thioacetamide on liver microsomal P450 enzymes were further investigated. Thioacetamide at 100 mg/kg/ was treated intraperitoneally for 6, 12, 24, 36, 48 and 72 hr. The blood was collected at the designated time for assaying the serum enzyme activities. To determine the P450 isozyme-specific activities. ethoxyresorufin O-deethylase (EROD), methoxyresorufin O-demethylase (MROD), and benzyloxyresorufin O-debenzylase (BROD) activities were determined for P450 1A1, 1A2 and 2B1, respectively, in liver microsomal fractions. The activities of ALT and AST were started to be elevated 6 hr after thioacetamide treatment andreached the maximun at 36 hr after the treatment. The elevated activities were dramatically recovered at 72 hr. The microscopic exmination of the liver specimen also showed a similar profile of hepatotoxicity. All P450-associated enzyme activities were time-dependently inhibited by the treatiment with thioacetamide. The maximum inhibition of P450 enzymes was observed 36 hr after the treatment. Because the inhibition of P450 enzymes by thioacetamide was time-dependent, our present results suggest that thioacetamide might inhibit P450 enzymes in mechanism-based inactivation.
Kim, Kap-Ho,Bae, Ju-Hyun,Cha, Shin-Woo,Han, Sang-Seop,Park, Kwan Ha,Jeong, Tae Cheon 영남대학교 약품개발연구소 2000 영남대학교 약품개발연구소 연구업적집 Vol.10 No.-
Effects of thioacetamide on antibody response to sheep red blood cells were investigated in male BALB/c mice. When mice were treated intraperitoneally with thioacetamide once, the antibody response was significantly suppressed at 200㎎/㎏ with hepatotoxicity. When mice were treated intraperitoneally with thioacetamide for 7 consecutive days, the antibody response was suppressed at 50㎎/㎏ without hepatotoxicity. To determine the possible role of metabolic activation by cytochrome P450 in thioacetamide-induced suppression of antibody response, mice were pretreated with phenobarbital intraperitioneally for 3 days, followed by intraperitoneal administration of 100 ㎎/㎏ of thioacetamide for 3 days. The elevated activities of serum aspartate aminotransferase and alanine aminotransferase by thioacetamide were potentiated by phenobarbital pretreatment. The suppression of antibody responsse by thioacetamide was potentiated by phenobarbital. In liver microsomes, the activities of P450 2B-specific enzymes were induced by phenobarbital. Our present results suggest that thioacetamide may require metabolic activation by P450 to its immunosuppressive form(s). ⓒ 2000 Elsevier Science Ireland Ltd. All rights reserved.
A Three-step Method of Immunotoxicity Assessment
Lee, Jeong Woon,Shin, Ki Duk,Kim, Kap Ho,Kim, Eun Joo,Han, Sang Seop,Jeong, Tae Cheon,Koh, Woo Suk 영남대학교 약품개발연구소 2001 영남대학교 약품개발연구소 연구업적집 Vol.11 No.-
The tmmunosuppresstue effects of thtrly nine chemlcals chosen by their potenttal toxtclty were evaluated using a three-step testing method. The lmmundotoxicity test method developed in this study conslsted of three stmple assays of lymphorprotiferatton, mixed leukocyte response, and interleuktn (IL)-2 production. The first stp was mitogen-lnduced prottferatton assay. Ten chemtcals showed the inhibttory effects on the mitogen (lipcpolysaccharlde of concanavaltn A)-lnduced proltferatton in dose-dependent manners. The second step was mixed lymphocyte response. This step crosschecked the growth-suppres-stve effects detected at the first step. All of 10 chemicals, which showed suppression of lymphoprottferation. also exhibited the suppressive effects on the mixed lymphocyte response in the similar range of chemical concentratton. The third step was planned to determine whether or not this growht suppression was medlated through an early activatton of T-cell, which could be represented with IL-2 production. Six out of 10 chemlcals decreased the interleukin-2 production in the simllar concentration range used in the step 1 and 2. These results suggest that those 6 chemtcals might have their targets on thesignal transduction pathway toward the IL-2 production. In the meantime the other 4 chemicals might have their targets after the IL-2 production signal. Taken all together, the three-step test would be simple, fast, and effcient to determine whether or not the chemical has immunosuppressive effects.