• Biomolecules & Therapeutics
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• v.10 no.1
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• pp.59-69
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• 2002

Recently, recombinant human erythropoietin (rHu-EPO) has been used to treat various types of anemia. YHB216 is a new rHu-EPO developed by Yuhan Research Institute. In this study, we investigated the single dose and 4-week repeated dose toxicity of YHB216 in Beagle dogs. In the single dose toxicity study, YHB216 was administered intravenously at single dose levels of 0 and 25,000 IU/kg to dogs (2 dogs/sex/group). There were no treament-related changes in survivals, clinical signs, body weight gain, hematological values, blood chemical values, and necropsy finding during experimental period. In the repeated dose toxicity study, YHB216 was administered intravenously to dogs for 4 weeks at the dose levels of 0, 100, 500, and 2,500IU／kg (3 dogs/sex／group). There were no toxicologically significant changes in clinical signs, body weights, food and water consumptions, ophthalmoscopy, urinalysis and blood chemistry. There were increased values of red blood cell, hemoglobin, and hematocrit at all treated groups. Spleen revealed increased weight and extramedullary hematopoiesis at 500 IU/kg or more. These changes are all considered to be Pharmacology-related effects and were recovered after 4-week recovery period. From these results, it is concluded that LD50 value was above 25,000 IU/kg in the single dose toxicity study of YHB216 in dogs and the no observed adverse effect level (NOAEL) was 100 IU/kg day in the repeated dose toxicity study of YHB216 in dogs.

• Korean Journal of Pharmacognosy
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• v.33 no.1 s.128
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• pp.5-12
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• 2002

This study was performed to evaluate hepatoprotective effect of Daewhang-whangryunhaedok-Tang(DWT) on liver injured rats induced by $CCl_4$ and the acute oral toxicity of it in mice. The activities of serum transaminase(ALT/AST), alkaline phosphatase(ALP) and lactic dehydrogenase (LDH), the levels of serum total cholesterol(TC) and triglyceride(TG), change of liver enlargement, and inhibitory activities of lipid peroxidation, catalase and glutathione-S-transferase(GST) in liver microsome were determined in hepatotoxic rats induced by $CCl_4$ DWT DWT was significantly reduced the serum ALT, AST, ALP, LDH, TC and TG levels. And, the increase of lipid peroxidation, decrease of catalase and GST activities in the liver microsome of $CCl_4$-intoxicated rat were significantly improved by the treatment of DWT. Male and female mice were administered maximum dosages of 5,000 mg/kg b.w. of DWT. After single oral administration of DWT to mice, we observed them daily for 2 weeks. DWT did not induce any toxic signs in the mortalities, clinical signs, body weight changes, and gross necropsy findings of mice. Based on these results, it is concluded that DWT may have the hepatoprotective effect on $CCl_4$ induced hepatotoxicity in rats. Also, DWT may have no side effect and its $LD_{50}$ value may be over 5,000 mg/kg b.w. in mice.

• Proceedings of the Korean Vacuum Society Conference
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• 2000.02a
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• pp.31-31
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• 2000

Al2O3는 높은 화학적, 열적 안정성으로 인하여 미세전자 산업에서 절연막이나 광전자소자의 재료로써 널리 이용되고 있다. 특히, 사파이어는 고위도의 LED, 청색 LD의 재료인 GaN 계열의 III-Nitride 물질을 성장시킬 때 필요한 기판으로 보편적으로 사용되고 있다. 이러한 GaN계열의 광소자 제조에서 사파이어 기판을 적용시 지적되는 문제점들 중의 하나는 소자제조 후 사파이어의 결정 구조 및 높은 경도에 의해 나타나는 cutting 및 backside의 기계적 연마가 어렵다는 것이다. 최근에는 이온빔 식각이나 이온 주입 후 화학적 습식 시각, reactive ion etching을 통한 사파이어의 건식 식각이 소자 분리 및 backside 공정을 우해 연구되고 있다. 그러나 이러한 방법을 이용한 사파이어의 식각속도는 일반적으로 15nm/min 보다 작다. 높은 식각율과 식각후 표면의 작은 거칠기를 수반한 사파이어의 플라즈마 식각은 소자 제조 공정시 소자의 isolation 및 lapping 후 연마 공정에 이용할 수 있다. 본 연구에서는 평판 유도결합형 플라즈마를 이용하여 Cl2/BCL3/Ar 의 가스조합, inductive power, bias voltage, 압력, 기판온도의 다양한 공정 변수를 통하여 (0001) 사파이어의 식각특성을 연구하였다. 사파이어의 식각속도는 inductive power, bias voltage, 그리고 기판 온도가 증가할수록 증가하였으며 Cl2에 BCl3를 50%이하로 첨가할 때 BCl3 첨가량이 증가할수록 식각속도 및 식각마스크(photoresist)와의 식각선택비가 증가하는 것을 관찰하였다. 또한, Cl3:BCl3=1:1의 조건에 따라 Ar 첨가에 따른 식각속도 및 표면 거칠기를 관찰하였다. 본 연구의 최적 식각조건인 40%Cl2/40%BCl3/20%Ar, 600W의 inductive power, -300V의 bias voltage, 30mTorr의 압력, 기판온도 7$0^{\circ}C$에서 270nm/min의 사파이어 식각속도를 얻을수 있었다. 그리고 이러한 식각조건에서 표면의 거치기를 줄일수 있었다. 사파이어 식각은 보편적인 사파이어 lapping 공정시 수반되어 형성된 표면의 거치기를 줄이기 위한 마지막 공정에 응용될수 있다. 사파이어의 식각시 나타나는 식각 부산물은 플라즈마 진단방비인 optical emission spectroscopy (OES)를 통하여 관찰하였고, 식각시 사파이어의 표면성분비 변화 및 표면의 화학적 결합은 X-ray photoelectron spectroscopy(XPS)를 사용하여 측정하였다. 시각 전, 후의 표면의 거칠기를 scanning electron microscopy(SEM)을 통하여 관찰하였다.

• Korean Journal of Pharmacognosy
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• v.29 no.2
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• pp.93-103
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• 1998

In order to investigate the reducing effect of velvet antler water extract (VAWE) on the toxicity of anti-cancer drug, cis-platin (CDDP) and mitomycin C (MMC), we examined effects of co-administration with VAWE and anti-cancer drugs on their toxicities. We recognized that $LD_{50}$ of CDDP/MMC were increased by co-administration with VAWE and them in mice. It was found that co-administration of VAWE and MMC increased the survival rate in mice treated by lethal dose of MMC. Also, co-administration of VAWE and CDDP/MMC inhibited decrease of the body weight and organ weight in mice intoxificated by CDDP/MMC. The increase of serum blood urea and serum creatinine levels in rats intoxicated by CDDP were significantly inhibited by the co-administrationin with VAWE and CDDP. The decrease of RBC and WBC in rats intoxificated by MMC were significantly inhibited by the co-administration with VAWE and MMC. These results suggest that the combined usage of VAWE and CDDP/MMC drugs may be a new method for prevented or minimized the toxicity of them.

• Natural Product Sciences
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• v.12 no.4
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• pp.247-253
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• 2006

The antitumor activity of crude saponin mixture obtained from Luffa tuberosa (Roxb.) (Fam; Cucurbitaceae) hairy roots (CSLT) in mice transplanted with Ehrlich ascites carcinoma (EAC) was investigated. The EAC-bearing mice receiving 150 and $300{\mu}g/kg$ body weight, (i.p) of CSLT have shown a dose dependent elevation in tumor-tree survival and a highest number of survivors were observed after administration of CSLT $(300{\mu}g/kg)$, which was considered as an optimum dose for its antineoplastic action. The mean survival time (MST) for this dose was approximately $47.1{\pm}0.74d$, when compared with $19.0{\pm}0.36d$ of untreated control. Administration of $300{\mu}g/kg$ CSLT resulted in 130% long-term increased survival time. The measurement of body weight, tumor volume, packed cell volume, viable and non-viable count indicated the efficacy of CSLT in tumor-bearing mice, there was a significant recovery in hematological profiles, and there was depletion in lipid peroxidation levels, and the antioxidant enzyme activities such as GSH, SOD and CAT were restored to near the normal levels. The CSLT was found to be devoid of conspicuous short-term toxicity in the mice when animals were intraperitoneally injected with 250, 500, 750 and $1000{\mu}g/kg$ bodyweight. The treated mice showed conspicuous toxic symptoms only at a dose of $1500{\mu}g/kg$. Mortality of the animals was monitored up to 14 d post drug treatment, $1/7^{th}$ of the $LD_{50}$ dose has been considered for the optimal antineoplastic activity.

• Korean Journal of Pharmacognosy
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• v.10 no.2
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• pp.61-67
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• 1979

Two pure saponin components, Panax saponin C (protopanaxatriol derivative, ginsenoside Re) and Panax saponin E (protopanaxadiol derivative, ginsenoside $Rb_l$) were isolated from Panax ginseng root and their acute toxicities in mice and antistress effects in rats were investigated. Average lethal doses $(LD_{50})$ of ginsenoside Re were 130mg/kg (i.v.), more than 1,000mg/kg (i.p.) and more than 1,500mg/kg (s.c.), respectively. Average lethal dose of ginsenoside $Rb_{1}$ was 243mg/kg intravenously. Adrenal ascorbic acid and cholesterol contents were significantly decreased when normal rats were exposed to heat $(40^{\circ}C)$ for 30 min. The reduction of the adrenal ascorbic acid and cholesterol contents in rats was partially prevented when the rats received the ginseng saponins prior to exposure to heat stress and most pronounced effects were observed in rats received ginsenoside Re. However, it was found that administration of ginseng alone, without stress, did not significantly change the ascorbic acid and cholesterol contents in adrenal glands. Eosinophil counts in the blood of the rats were elevated when the rats were exposed to the heat stress, and the elevation of the eosinophil counts were prevented with the ginseng saponins under the stress, but the changes were all insignificant statistically.

• Toxicological Research
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• v.8 no.2
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• pp.161-170
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• 1992

The objectives of this sutdy were to investigate the effects of 8-fluorociprofloxacin(8-FCP) on the central nervous system (CNS) and to compare with those of ciprofloxacin(CP). The $LD_{50}$ values of intravenous 8-FCP were similar or slightly lower in rat (M;203.6mg/kg, F;186.1mg/kg)and markedly lower in mice (M;126.5mg/kg, F;163.1mg/kg), as compared to those of CP. However, no recognizable differences in the clinical signs and recovery were found between 8-FCP and CP in both species. In combination with fenbufen, the convulsive liability of 8-FCP was higher than that of CP. At an intravenous dose of 10mg/kg, 8-FCP provoked convulsive signs and subsequent death in mice, whereas CP produced convulsion at a dose of 40mg/kg. The hexobabital -induced sleeping time was markedly lengthened by the oral administration of 8-FCP, but slightly increased by CP. In addition, the two quinolone derivatives had analgesic effects. The analgesic activity of 8-FCP was approximately two times higher than that at CP. However, both 8-FCP and CP had little effects of pentylenetetrazole-or strychnine-induced convulsion and muscle relaxation. Our finding that 8-FCP had more remarkable CNS effects than CP strongly suggests that there should be differences in the pharmacokinetic characteristics and/or in the binding affinity for specific biologic targets, or receptors, in the CNS.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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• pp.178-178
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• 1998

We reported that the hexane fraction of Torilis Fructus have an anti-inflammatory and analgesic effect. Therefore, in order to isolate the active compound, the hexan fraction of Torilis Fructus was chromatographed on silica gel column. The subfraction of hexane fraction was crystallized as colorless stout needles. The chemical structure of this compound was verified to be torilin through m.p., UV, IR, GC-MS, and NMR spectral data. In pharmacological tests, torilin exhibited strong anticarrageenan activity at the dose of 90 and 270 mg/kg, p.o. in rats, and it had inhibitory effect on the vascular permeability at the dose of 30 and 90 mg/kg, p.o. in mice. Torilin showed potent inhibition of leucocyte emigration in CMC-pouch at the dose of 3 and 9 mg/rat, s.c. Torilin have the analgesic effect at the dose of 30, 90 and 270 mg/kg, p.o. in both of the acetic acid- and phenyl-p-benzoquinone-induced writhing syndrome. It also increased the pain threshold at the dose of 30, 90 and 270 mg/kg, p.o. in the tail pressure method and the Randall-Selitto method. Torilin did not show a hypothermic action at the dose of 30 and 90 mg/kg, p.o. in mice. The acute toxicity of torilin was very weak: the LD$\_$50/ value was more than 5000 mg/kg, p.o. and 2000 mg/kg, Lp. in mice. From the above mentioned results, it was suggested that torilin had potent anti-inflammatory and analgesic activities in animals.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1998.11a
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• pp.190-190
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• 1998

$_2$(5,7-dipropoxychrysin), $B_1$(chrysin7-O-toluate), $T_{0}$(5-hydroxy-7-butoxy-chrysin), and $O_1$(5- hydroxy-7 -octoxychrysin) are chrysin derivatives which have isolated from Mori Cortex Radicis. They exhibited strong hypoglycemic effect, so they can be developed for hypoglycemic agents. In this study, we evaluated the acute toxicity of $P_2$, $B_1$, $T_{0}$, and $O_1$ by a single oral administration in rats and mice. The male SD rats and the male ICR mice were divided into 5 groups, and each group was treated orally with 500mg/kg $P_2$, $B_1$, $T_{0}$, and $O_1$, and control respectively. 500mg/kg is the highest dosage which can be administered to mouse. Each group of mice were subdivided as the dosage, 5mg/kg, 20mg/kg, l00mg/kg, and 500mg/kg. After oral administration, we examined food consumption, clinical signs and mortality of each group for 12 days. We also examined body weight increment of animals before and after treatment. Then organ weights were examined on 13th day. There was no toxic effect in mortality, body weight changes, food consumption, clinical signs and organ weights. We found out that the $LD_{50}$ of $P_2$, $B_1$, $T_{0}$, and $O_1$ is more than 500mg/kg in rats.

• The Journal of the Korean Society for Microbiology
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• v.21 no.4
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• pp.407-415
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• 1986

This study investigated whether a correlation exists between environmental physical and biochemical factors and adherence of Candida albicans to human buccal epithelial cells by using normal and UV-irradiated strains. The results were as follows: 1. The percentage of germ tube forming activities of normal Candida albicans was 91.5% and UV-irradiated Candida albicans was 15.0%. The $LD_{50}$ of normal strains in mice were $1.0{\times}10\;cells/ml$, but could not be observed in the UV-irradiated strains even with $1.0{\times}10\;cells/ml$. It demonstrated that the virulence is decreased in the UV-irradiated strain. 2. The adherence of normal Candida albicans to human buccal epithelial cells($166{\pm}29{\sim}207{\pm}17\;cells$/100 epithelial cells) was significantly greater than UV-irradiated Candida albicans($99{\pm}21{\sim}131{\pm}25\;cells$/100 epithelial cells). 3. Candida albicans cultured at $37^{\circ}C$ adhered to buccal epithelial cells($166{\pm}16{\sim}207{\pm}17\;cells$/100 epithelial cells) in greater numbers than cultured at $25^{\circ}C$($80{\pm}15{\sim}143{\pm}22\;cells$/100 epithelial cells). 4. On comparison of the adherence of viable and nonviable(heat-killed) Candida albicans to human buccal epithelial cells, the nonviable Candida albicans demonstrated poorer adherence than viable Candida albicans. 5. Adherence in vitro of Candida albicans to human epithelial cells appeared to be effected by the pH. The adherence ability was maximum increased at pH 7.0($187{\pm}22\;cells$/100 epithelial cells) other than experimental pH. 6. The adherence was proportional to the incubation time and the Candida cell concentration in the suspension. 7. A strong correlation was shown between germ tube forming activity and increased adherence of Candida albicans to human epithelial cells, indicating that germ tube forming activity were responsible for candidal virulence.