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새로운 안트라사이클린계 항암제 DA-125 의 생식독성연구 토끼 최기형시험
정문구(Moon Koo Chung),김종춘(Jong Choon Kim),한상섭(Sang Seop Han),노정구(Jung Koo Roh) 한국응용약물학회 1995 Biomolecules & Therapeutics(구 응용약물학회지) Vol.3 No.1
DA-125, a new anthracycline antitumor antibiotic, was administered at dose levels of 0, 0.2, 0.6 and 1.8 mg/kg/day intravenously to pregnant New Zealand White rabbits from day 6 through 18 of gestation. The does were subjected to the caesarean section on day 28 of gestation. Effects of test agent on general toxicity of does and embryonic development of F1 fetuses were examined. At 1.8 mg/kg, the organ weight for ovary of does was significantly decreased. The decrease in the number of corpus lutea, implantations and litter size, and the increase in the rate of resorptions were also observed. In addition, various types of external, visceral and skeletal malformations occurred in fetuses at an incidence of 7.7, 7.7 and 20.6 %, respectively. The results show that the no effect dose levels (NOELs) of DA-125 are 0.6 mg/kg/day for does and F1 fetuses.
복합항생제 SM-101 ( 설박탐 , 메탐피실린 ) 의 생식독성연구 랫트 수태능력시험
정문구(Moon Koo Chung),송시환(Si Whan Song),노정구(Jung Koo Roh) 한국응용약물학회 1996 Biomolecules & Therapeutics(구 응용약물학회지) Vol.4 No.1
A new composite antibiotic, SM-101(sulbactam·metampicillin), was at dose levels of 0, 250, 500 and 1000 ㎎/㎏/day administered intravenously to Sprague-Dawley male rats from premating to mating period and to females from premating to early gestation period. Effects of test agent on general findings and reproductive performance of parent animals and embryonic development were examined. In male parents, two deaths occurred at 1000 ㎎/㎏. The increase in kidney weight of the 1000 ㎎/㎏ group were also observed. The decrease in body weight and food consumption were found at 500 and 1000 ㎎/㎏. The decrease in spleen weight were seen at 250, 500 and 1000 ㎎/㎏. In female parents, three deaths were found at 1000 ㎎/㎏. Mating performance and fertility of parent animals were not adversely affected by all doses tested. F1 fetuses showed no changes related to treatment of SM-101. The results show that the no effect dose level(NOEL) for general toxicity of parent animals is under 250 ㎎/㎏/day and NOELs for reproductive capability and fetal development are over 1000 ㎎/㎏/day.
새로운 안트라사이클린계 항암제 DA-125 의 생식독성연구 (2) 랫트 최기형시험
정문구(Moon Koo Chung),김종춘(Jong Choon Kim),김원배(Won Bae Kim),노정구(Jung Koo Rho) 한국응용약물학회 1994 Biomolecules & Therapeutics(구 응용약물학회지) Vol.2 No.1
DA-125, a new anthracycline antitumor antibiotic, was at dose levels of 0, 0.03, 0.1 and 0.3 mg/kg/day administered intravenously to Sprague-Dawley male rats from premating to mating period and to females from premating to early gestation period. Effects of test agent on general findings and reproductive performance of parent animals and embryonic development were examined. No treatment-related changes in clinical signs, body weight, food consumption and necropsy findings were observed in all groups of both sexes. At 0.3 mg/kg, a decrease in the weight of spleen was found only in male rats. Mating performance and fertility of parent animals were not adversely affected by all doses tested. Fl fetuses showed no changes related to treatment of DA-125, except that at 0.3 mg/kg, an increase in the resorption rate was seen. The results show that the no effect dose levels (NOELs) for general toxicity of parent animals and fetal development are 0.1 mg/kg/day and NOELs for reproductive capability are over 0.3 mg/kg/day.
새로운 안트라사이클린계 항암제 DA-125 의 생식독성연구 랫트 주산기 및 수유기시험
정문구(Moon Koo Chung),이순복(Soon Bok Lee),한상섭(Sang Seop Han),노정구(Jung Koo Roh) 한국응용약물학회 1995 Biomolecules & Therapeutics(구 응용약물학회지) Vol.3 No.1
DA-125, a new anthracycline antitumor antibiotic, was administered at dose levels of 0, 0.04, 0.2 and 1.0 mg/kg/day intravenously to pregnant and subsequently delivered Sprague-Dawley rats from day 17 of gestation to day 21 of lactation. Effects of test agent on general toxicity of dams and growth, behaviour and mating performance of F1 offspring were examined. At 1 mg/kg, one out of the twenfytwo dams showed difficult delivery, characterised by a stillbirth. Reduction in body weight, loss in food intake, and decrease in spleen weight were also observed in dams. In addition, the lower rates of successful performances in memory test (28.6%) and necrosis of tail end (9.5%) were seen in F1 offspring. At 0.04 and 0.2 mg/kg, no toxic effect on dams and F1 offspring was observed. There were no malformed F1 and F2 fetuses in all groups. The results indicate that the no effect dose levels(NOELs) of DA-125 are 0.2 mg/kg/day for dams and F1 offspring, and over 1 mg/kg/day for F2 fetuses.
새로운 안트라사이클린계 항암제 DA-125 의 생식독성연구 (1) 랫트 최기형시험
정문구(Moon Koo Chung),한상섭(Sang Seop Han),양중익(Jung Ick Yang),노정구(Jung Koo Rho) 한국응용약물학회 1994 Biomolecules & Therapeutics(구 응용약물학회지) Vol.2 No.1
DA-125, a new anthracycline antitumor antibiotic, was at dose levels of 0, 0.1, 0.3 and 1.0 mg/kg/day administered intravenously to pregnant Sprague-Dawley rats during the organogenetic period. Two-third of dams per group were subjected to caesarean section on day 20 of pregnancy and the remaining 10 dams per group were allowed to deliver. Effects of test substance on dams, embryonal development of F1 fetuses, as well as growth, behaviour and mating performance of F1 offspring were examined. 1. At 1 mg/kg, one out of the 10 dams showed difficult delivery. A decrease in food consumption, a loss in body weight and a decrease of spleen weight were found in this dose level group. At 0.3 mg/kg, difficult deliverys were observed in two out of the 10 dams. 2. At 1 mg/kg, an increased resorption rate and a decreased fetal weight were found. In addition, various types of external, visceral and skeletal malformations occurred at an incidence of 11.9, 41.8 and 14.5%, respectively. 3. At 1 mg/kg, body weight reduction, small eyeball, hydrocephalus and atrophy of sexual organs were observed in F1 offspring. One male pup receiving 0.3 mg/kg died on day 2 of lactation. The results show that the no-effect dose levels (NOELs) for dams and F1 offspring are 0.1 mg/kg/day and NOEL for F1 fetuses is 0.3 mg/kg/day.
랫드에 있어서 배양배자에 대한 Phenytoin의 최기형성 효과
김종춘,임광현,정문구,노정구,Kim, Jong-Choon,Lim, Kwang-Hyeon,Chung, Moon-Koo,Roh, Jung-Koo 한국독성학회 1998 Toxicological Research Vol.14 No.3
The teratogenic potential of the anticonvulsant drug phenytoin (PHT) has been well documented both in the human and in the experimental animals. However there are few reports on the effects of PHT on embryonic development in rats in vitro. The present study was performed to evaluate the teratogenic effects of PHT using whole-embryo culture system in rats. Sprague-Dawley rat embryos were explanted on gestational day (GD) 9.5 and cultured for 48 hrs in the immediately centrifuged and heat-inactivated rat serum containing 0,25,50, or $100{\mu}g$ PHT/mL. At the end of culture period the embryos were scored for morphological development according to the procedure of Van Maele-Fabry, and their total protein contents were determined. At 100 ${\mu}$g/mL of culture medium. PHT caused significant reduction in developmental score and protein content of embryos and a high incidence morphological abnormalities (100%). Characteristic malformations included altered yolk and embryonic circulation, craniofacial hypoplasia, neural tube schisis, branchial arch defects, abnormal ratation, and limb bud hypoplasia, among others. There were no adverse effects on embryonic growth and development at concentrations of 25 and 50 ${\mu}$g /mL of culture medium. The results indicated that the dysmorphogenic effect of PHT on cultured embryos is due to a direct interference with embryonic development.