• Title/Summary/Keyword: 반복투여

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Preparation and In Vitro Release of DNA-Loaded Poly(D,L-lactic-co-glycolic acid) Microspheres (DNA가 봉입된 Poly(D,L-lactic-co-glycolic acid) 미립구의 제조 및 시험관내 방출)

  • Son, Hye-Jung;Kim, Jin-Seok
    • Polymer(Korea)
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    • v.29 no.1
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    • pp.69-73
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    • 2005
  • To overcome the main disadvantages of non-viral gene delivery systems such as repeated administration due to the low transfection efficiency, poly(D,L-lactide-co-glycolide) was applied to encapsulate pDNA in its microsphere formulation. Free pDNA or various ratios (w/w) of chitosan/pDNA complexes was used for encapsulation, with the resulting encapsulation efficiency of 44%, 5%, and 8% for free pDNA, 0.7:1 and 1:1 ratios, respectively. Scanning electron micrographs of poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres encapsulating pDNA or chitosan-condensed pDNA revealed a smooth spherical shape immediately after microsphere preparation and a collapsed porous shape in 41 days due to the degradation of PLGA. In vitro release profile showed that the 0.7:1 (w/w) ratio formulation exerted 47% release in 26 days, whereas free pDNA or 1:1 (w/w) ratio formulation did only 15% or 32%, respectively.

Single and 4-Week Repeated Dose Toxicity Studies of DA-3585, a Recombinant Human Erythropoietin, in Rabbits (사람 적혈구 조혈인자 DA-3585의 토끼에 대한 단회 및 4주 반복투여 독성시험)

  • Cho, Hyeon;Kim, Dong-Hwan;Kang, Kyung-Koo;Baik, Nam-Gi;Kim, Won-Bae
    • Biomolecules & Therapeutics
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    • v.6 no.2
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    • pp.171-181
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    • 1998
  • DA-3585, a biosynthetic recombinant human erythropoietin has been developed as a treatment for anemia associated with chronic renal failure in Dong-A pharmaceutical Co. Ltd. This study was carried out to assess its acute and subacute toxicities in rabbits. DA-3585 was intravenously administered to rabbits at dose levels of 6250, 12500 or 25000 lU/kg for single dose toxicity study and at dose levels of 100, 500 or 2500 lU/kg/day for 4-week repeated dose toxicity study. In the acute toxicity study, dose up to 25000 lU/kg had no adverse effect on the behavior or body weight gain. Pathological examinations revealed no abnormal gross lesions related to DA-3585. In the subacute toxicity study, all animals survived until termination of treatment. DA-3585 had no influence on clinical signs, food and water intake or on body weight changes. Hematological examination showed increases in the number of RBC, hemoglobin contents and hematocrit values with a dose dependent manner in the animals treated with DA-3585. Histopathological examination revealed erythroid hyperplasia in the bone marrow and extramedullary hematopoiesis in the liver. The changes detected in the hematological and histopathological examination presumably represent exaggerated pharmacological effects of erythropoietin. The NOAEL (no-observed-adverse-effect-level) of DA-3585 was estimated to be 100 lU/kg/ day under this study condition.

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Effects of Repeated Superovulation on Recovery and Quality of Oocytes in Korean Native Goats (재래산양의 반복 과배란처리에 의한 난자의 회수율과 등급에 관한 연구)

  • Park, H.-S.;Lee, Y.-H.;Kim, T.-S.;Park, J.-K.;Lee, J.-S.;Kim, C.-H.;Jung, J.-Y.
    • Journal of Embryo Transfer
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    • v.19 no.2
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    • pp.81-87
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    • 2004
  • This study was designed to determine whether repeated superovulation is beneficial for recovery and quality of oocytes in Korean native goats. Seventy-six mature goats, maintained in a pen under natural day length and fed hay ad libitum, were pretreated with progestagen impregnated CIDR for 10 days and then the goats were divided into two groups. One group of the goats received a single intramuscular injection of 1,000 IU PMSG on Day 8 of CIDR insertion. The other group of the goats received twice daily intramuscular injections of a total of 70 mg FSH for 3 days from Day 8 of CIDR. All the gonadotropin treated goats were injected with 10 mg $PGF2{\alpha}on$ Day 8 and 400 IU hCG in the afternoon on Day 10. For oocyte recovery, donor goats were fasted 24 h before operation. Anesthesia was induced by intravenous injection of 2% xylazine(0.2 mg/kg body weight) and ketamin(11 mg/kg body weight). In vivo oocytes were recovered by follicle aspiration or oviduct flushing at 35 to 40 hours after hCG injection through mid-ventral incision. The mean number of CL and oocytes recovered and recovery rate of oocytes by oviduct flushing were greater(P<0.05) in the first treatment than those in the second treatment. Contrary to our assumption, PMSG treatment significantly (P<0.05) increased the number of CL formed and recovery rate of oocytes compared to FSH. However, the same effect was not observed in recovery of follicular oocytes. There was no significant difference in oocyte quality between FSH and PMSG or first and second treatments. The present results indicate that repeated superovulation and repeated use of donor animals may be inefficient for obtaining oocytes in good qualities.

Toxicity of DWP-301 ($Al(OH)_3\;Mg(OH)_2$, Simethicone, Aceglutamide Aluminum) to Rats by Repeated Oral Administration for 4 Weeks (DWP-301 (수산화알루미늄, 수산화마그네슘, Simethicone, Aceglutamide Aluminum)의 흰쥐에 대한 4주간 반복 경구투여 독연구)

  • Kim, Eun-Joo;Song, Si-Whan
    • YAKHAK HOEJI
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    • v.38 no.1
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    • pp.46-56
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    • 1994
  • Daily oral administration to Sprague Dawly rats for 4 weeks of DWP-301, at doses of 0, 500, 1000, 2000 mg/kg presented following results; 1) No animals died and there were no significant differences in general signs, body weight, food consumption, urinalysis haematological, biochemical, gross pathological and histopathological examination between control and treated rats. 2) Water consumption, pH-, protein- urobilinogen-, ketone-values in urine were significantly increased in the treated male and female rats. It is supposed that these differences in animals are a consistent feature of repeated overdosage with test suspensions. The results indicate that the non toxic dose of test compounds in rats is over 2000 mg/kg in this test system.

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Stability of Paclitaxel with Cephalosporines in $0.9\%$ Sodium Chloride Injection and $5\%$ Dextrose Injection During Simulated Y-Site Administration (Y-Site 동시투여 동안 $0.9\%$ 생리식염수와 $5\%$ 포도당 용액에서의 Paclitaxel과 Cephalosporines의 안전성 연구)

  • Burm, Jin Pil
    • Korean Journal of Clinical Pharmacy
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    • v.13 no.2
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    • pp.91-96
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    • 2003
  • Paclitaxel과 cephalosporines(제 1세대인 ceftezole sodium과 cephradine, 제2세대인 cefamandole sodium과 cefmetazole sodium, 제3세대인 cefoperazone sodium과 cefotaxime sodium 그러고 제4세대인 cefepime hydrochloride)을 $5\%$포도당주사액 그리고 $0.9\%$ 염화나트륨주사액과 함께 Y-Site 장치를 써서 환자에게 주입할 때 paclitaxel의 안정성에 관하여 연구하였다. Paclitaxel 0.3 mg/ml 및 1.2 mg/ml과 cephalosporines 20 mg/m을 각각 1 : 1로 혼합한 후 0, 1, 2, 4, 12시간 시점에서 paclitaxel의 농도를 HPLC로 분석하였다. 방해물질에 의한 분석오차를 줄이기 위해 분석법을 여러 상태에서 확인하였으며, 각 농도에서 3차례씩 실험하였고 각 샘플은 2차례 반복하여 HPLC로 분석하였다. 분석전에 각 시료의 투명도, 색의 변화, 침전상태 및 pH를 검사하였다. Paclitaxel 0.3 mg/ml 및 1.2 mg/ml와 cephalosporines 20 mg/ml를 각각 혼합하였을 때 12시간 동안 안정하였으며, 주사액의 혼탁이나 색의 변화 및 침전은 나타나지 않았으며 pH도 변하지 않았다.

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Excretion, Tissue Distribution and Toxicities of Titanium Oxide Nanoparticles in Rats after Oral Administration over Five Consecutive Days (티타늄나노입자의 랫드 5일 반복 경구투여 후 배설, 조직분포 및 독성에 관한 평가연구)

  • Kim, Hyejin;Park, Kwangsik
    • Journal of Environmental Health Sciences
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    • v.40 no.4
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    • pp.294-303
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    • 2014
  • Objectives: Excretion and tissue distribution of titanium oxide nanoparticles were evaluated in rats after oral administration. The relation between toxicity and systemic concentration of nanoparaticles was investigated. Methods: Rats were orally treated with titanium oxide nanoparticles (10, 100 mg/kg) for five consecutive days. General toxicity, blood chemistry, and serum biochemical analysis were analyzed. Titanium concentration in liver, kidney, lung, urine and feces were measured and histopathology was performed in these organs. Results: Induction of toxicological parameters was not observed and titanium nanoparticles were excreted via feces. Conclusion: Absorption of titanium oxide nanoparticles via the gastrointestinal tract after oral administration was very poor and systemic concentration of titanium oxide nanoparticles was not elevated. Titanium oxide nanoparticles did not cause toxicities in rats after oral administration.

Effects of Repeated Exposure to Pb Acetate on Hematopoietic Function, Testis and Kidney in Male Rats (Pb acetate의 13주 반복투여가 랫드의 조혈기능, 정소 및 신장에 미치는 영향)

  • 홍충만
    • Toxicological Research
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    • v.17 no.4
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    • pp.309-316
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    • 2001
  • Male Sprague Dawley rats were exposed to 0, 0.04, 0.2, and 0.8% Pb acetate in drinking water for 13 weeks and fed a commercial diet. Dose-related adverse effects observed at the end of the Pb acetate exposure in the drinking water were as follows: decrease in body weight gain, decrease in hemoglobin, hematocrit(HCT), mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH), increase in serum glucose, decrease in serum testosterone, increase in lead accumulation and $\delta$-ALA release in urine, and decrease in $\delta$-ALAD activities DNA content and histopathlogy (intranuclear inclusion body in kidney proximal tubule cell). Taken together, repeated exposure of lead acetate induced toxicities in hematopoietic system, especially testis and kidney.

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IPAA의 효과를 고찰하기 위한 분류분석방법들의 비교연구

  • Lee, Seung-Yeon;Lee, Eun-Ju;Choe, Ho-Sik
    • Proceedings of the Korean Statistical Society Conference
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    • 2005.05a
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    • pp.291-298
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    • 2005
  • 지속성 외래 복막투석은 말기 신부전 환자들에게 널리 시행하는 신 대체 요법으로, 복막투석 환자에게서 주된 합병증으로 일어나는 단백질-열량 영양실조를 치료하기 위하여 아미노산을 복강 내로 주입하는 치료방법이다. 이현석 등(2004)의 연구에서는 아미노산 복막 투석액(IPAA)이 영양실조 환자들에게 실제로 영양상태에 미치는 영향을 평가하기 위하여 지속성 외래 복막투석 환자 43명을 12개월 동안 3개월 주기로 관측하여 얻어낸 반복측정자료를 바탕으로 IPAA의 효과 여부에 따라 반응군과 비반응군을 분류하였다. 본 논문에서는 이러한 두 그룹을 효과적으로 분류할 수 있는 분류기준변수들을 찾아내고 이 분류기준변수의 값을 바탕으로 새로운 환자에게 IPAA의 투여 여부를 진단할 수 있는 여러 분류방법들을 고찰하여 비교 연구하였다. 모수적인 방법으로 선형판별분석, 이차판별분석 및 로지스틱 판별분석을 소개하고 비모수적인 방법으로 support vector machine(SVM)을 소개하여 분류분석의 결과를 비교하여 두 그룹을 최소한의 오류로 분류하는 방법을 제안하였다.

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동시획득 T1/T2 강조 경사자장 펄스열을 이용한 근골격계에서의 종양 관류 영상: 예비보고

  • 허용민;서진석;김대용;김은주
    • Proceedings of the KSMRM Conference
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    • 2002.11a
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    • pp.137-137
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    • 2002
  • 목적: 동시획득 T1/T2 강조 경사자장 펄스열을 이용하여 근골격계의 종양 관류 평가를 하고자 한다. 대상 및 방법: 근골격계 양성 및 악성 종양을 대상으로 동시획득 T1/T2 강조 경사자장 펄스열을 이용하여 시간해상도를 1.2초로 하여 1000회(약20분)를 반복하여 역동적 영상을 얻는다. 각각의 TR/TE1/TE2는 10/2/8 msec이다. 각 시기에서 서로 다른 TE를 가지고 있는 두 개의 영상을 이용하여, 수학적으로 분리하여 T1과 T2 값을 얻고, 이를 시간에 따라 배열한다. 이를 통하여, T2의 경우에는 일차효과를 이용하여 조직관류량(tissue blood volume)을 측정하고, T1에서는 2구획모델을 이용하여 투과도(permeability)를 측정한다.

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Mitogenic and Cytotoxic Effect of pure Fumonisin B$_1$, a carcinogen, in Sprague-Dawley Rats. (Fumonisin B$_1$의 SD흰쥐에 대한 세포분열과 세포독성작용)

  • Lim, Chae Woong;Has;Rim, Byung Moo
    • Environmental Mutagens and Carcinogens
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    • v.16 no.1
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    • pp.1-5
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    • 1996
  • Fumonisin B$_1$ is hepatotoxic in all species, but liver carcinogenic and nephrotoxic in rat. Our objective was to investigate the effects of multiple iv dose of FB$_1$. Male Sprague-Dawley rats were injected intravenously (iv) with FB$_1$ at 1 mg/kg singly (T1), or daily for 2 (T2) or 3 (T3). T1 rats did not show any cytotoxicity in both liver and kidney. However, the most dramatic change occurred in this group was mitotic figures in liver, which increased 5.5-fold to that of control. Hepatotoxic effects were shown in T3, based on histopathology and serum chemistry. A few scattered single cell deaths occurred primarily in the centrilobular area of the liver in T2. Similar but more lesions in liver and a small number of degenerating cells with hypereosinophilic cytoplasm in outer stripe of medulla of kideny were found in T3 rats. Serum chemical profiles included liver enzymes increased, in which cholesterol was very sensitive. This study suggests that multiple exposure of low dose FB$_1$ cause cytotoxic in the liver earlier time point than kideny. FB$_1$$ also stimulates mitosis in liver that may be associated with carcinogenesis.

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