• 대한수의학회지
• /
• 제43권1호
• /
• pp.57-66
• /
• 2003

Single and 28-day repeated dose toxicity studies of botulimnn toxin type A were carried out in ICR mice and Sprague-Dawley rats, respectively. In the single dose toxicity study, botulinwn toxin was injected intraperitoneally to male and female mice at a single dose of 40, 59, 89 133 and 200 ng/10 ml saline/kg. All animals died from 59 ng/kg group. Some clinical signs, such as decrease in locomotor activity, dyspnea, prone position and ptosis, were observed in most of both sexes from 59 ng/kg group, but no signs were seen in all animals at 40 ng/kg group. The results showed that the median lethal dose of botulinum toxin might be in the range of 40-59 ng/kg in both sexes. In the repeated dose toxicity study, the test material was administered intradermally for 28 days at doses of 0 (vehicle-treated control), 1.25, 2.5, 5.0 and $10.0ng/head/50{\mu}{\ell}$ saline in male and female rats. No test material-related changes were noted in survivals, clinical signs, food and water consumptions and gross finding in any group. Botulinum toxin treatment significantly decreased the body weight gain rate in male of 5.0 ng/head group and over and in female of 10.0 ng/head group compared to vehicle-treated control. One or more relative organ weights (i.e., spleen, thymus, liver and kidney) were increased significantly from 5.0 ng/head group compared to vehicle-treated control in both sexes. Serum biochemistry revealed increases in aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatine phosphokinase, total protein and albumin in male, and increases in AST and ALT and decreases in $K^+$ and $Cl^-$ in female without dose-pendent manners. In the histopathological study, physical stimulation by needle caused slight inflammations of dennis. In addition, botulinum toxin treatment induced denervation of nerve cell and disuse of muscle, resulting in atrophy of skeletal muscle in both sexes from 2.5 ng/head group. When the antibodies to toxin were determined in all animals, a significant increase in serum antibodies was observed from 5.0 ng/head group. The results showed that the NOAEL of botulinum toxin might be 1.25 ng/head for 28-day repeated dose toxicity in rats.

• Clinical and Experimental Reproductive Medicine
• /
• 제18권2호
• /
• pp.153-162
• /
• 1991

The present study was undertaken to clarify the role of calcium ion as a factor for the maturation of follicle-enclosed mouse oocytes. Follicles were isolated with two sharp needles under a stereomicroscope from mouse(ICR) ovaries which were treated PMSG 5 IU 45 hours previously. Isolated follicles were cultured for 14-16 hours in an organ culture system at $37^{\circ}C$, 5% $CO_2$ in air and in a 100% humidified incubator by treatment of hCG, EDTA and $^{45}Ca^{++}$. Culture medium was Modified Hank's Balanced Salt Sol. (MHBS) and addition of hCG (human chorionic gonadotropin) was made into two doses level 0.4 IU and 0.8IU from the stock sol. and also $^{45}Ca^{++}$ was treated in the culture medium. To explain the role of calcium, calcium chelating agent EDTA was treated to the culture of the mouse follicle-enclosed oocytes. Two observations were made in the present study; nucleus phase and $^{45}Ca^{++}$ uptake into the oocyte. HCG induced oocyte maturation in the follicle about two folds as much as the control group, whereas there is no difference in oocyte maturation between 0.4 IU and 0.8 IU of hCG. Optimum level of hCG seems to be 0.4 IU/ml in the mouse follicle culture. HCG stimulated $^{45}Ca^{++}$ uptake into the oocyte of the follicles by two folds. $^{45}Ca^{++}$ uptake in the control group is about 2.5 folds in comparison of the EDTA(1.71mM) treated group. However, calcium uptake in the EDTA treated groups tends to increase depending on the decrease of EDTA concentration. These observations suggest that firstly, hCG stimulates maturation of the oocyte of the follicle, secondly, $Ca^{++}$ influx is induced by hCG and thirdly, $Ca^{++}$ influx by the treatment of EDTA decreases as a dosage-dependent process. This $Ca^{++}$ uptake may take place by the changes of permeability which was induced by hCG treatment. That is, $Ca^{++}$ influx may trigger the resumption of oocyte maturation. It is further necessary in the future study how this $Ca^{++}$ uptake is induced by hCG and increases permeability of the follicle and oocyte.

• 한국의학물리학회지:의학물리
• /
• 제9권4호
• /
• pp.201-206
• /
• 1998

세기변조방사선치료 (Intensity Modulation Radiation Therapy; IMRT) 의 치료계획 목적으로 사용하기 위한 선량최적화 방법을 Gradient based algorithm을 이용하여 개발하였다. 환자의 치료 관심 부위를 포함하는 약 10-30 CT 단면에 대하여 각 단면 별로 선량최적화를 실시하였고, 장기별로 최대 허용선량을 지정하였으며, 표적의 선량은 100$\pm$5 %로 제한하였다. beamlet의 크기는 8$\times$8 $cm^2$으로 제한하였고, beam size가 크지 않으므로 beam diverge는 고려하지 않았다. beamlet 하나가 만드는 선량분포를 미리 계산한 후, 선량중첩방식으로 전체 선량분포를 계산하였다. 고정된 동일평면에 대하여 5방향에서 입사하는 빔에 대한 최적화를 실시하였으며, 그 효용성을 비교하기 위해, 1, 3, 5, 7, 9 방향에 입사하는 빔과 최적화지수를 구하였다. 선량최적화에 소요되는 시간은 대체로 slice 수에 비례하였으며, 계산시간과 최적화지수를 비교할 때 빔의 개수가 3-7개 일 때 가장 적합하였다. 다중단면에 대한 선량최적화를 beam divergence를 고려하지 않을 때, 단일 단면에 대한 선량최적화를 반복 시행함으로써 얻을 수 있었다. 선량최적화의 결과가 선량중심의 위치에 따라 민감하게 변하는 경우가 발생하였으며, 이를 개선하기 위해서는 선량중심의 최적화가 개발될 필요성이 있었다.

• 한국의학물리학회지:의학물리
• /
• 제16권4호
• /
• pp.161-165
• /
• 2005

CT 기종에 따라서 전자밀도에 대응하는 CT 수의 변화와 치료계획 시 선량계산에 미치는 영향을 분석하였다. 5종의 CT를 이용하여 전자밀도 교정 팬톰의 영상을 얻어 기종에 따른 CT 수의 변화를 알아보았다. 조직등가물질의 밀도에서 CT 수는 ${\pm}2\%$ 내의 차이를 보였으나 밀도가 큰 영역에서는 최대 $9.5\%$의 차이를 나타냈다. CT 수의 변화가 치료계획의 선량계산에 미치는 영향을 알아보기 위하여 환자의 흉부 영상을 이용하여 장기별로 선량의 차이를 분석한 결과 최대 $0.48\%$로 거의 차이를 보이지 않았다. 밀도가 큰 물질이 인체 내에 삽입되어 있을 경우를 가정하여 물팬톰에 CT 수가 2,000인 고밀도 물질을 삽입한 팬톰 영상을 치료계획장치에 그려 넣었다. 고밀도 물질 아래 20 cm 깊이에서 선량 계산을 비교한 결과 $2.1\%$의 차이를 보였다. 치료계획 단계에서 선량 불확도를 최소화하기 위해서는 사용되는 CT 기종에 따른 CT수와 전자밀도의 정확한 환산이 필요하며, 특히 한 기관에서 여러 종류의 CT를 이용하는 경우 각 CT 별로 전자밀도에 대응하는 CT 수를 입력하고 서로 구별하여 사용하여야한다. 또한 CT수의 재현성을 확인하기 위해 주기적인 점검이 요구된다.

• 대한한의학회지
• /
• 제38권2호
• /
• pp.15-30
• /
• 2017

Objectives: Hwangryunhaedok-tang (HHT; Huanglianjiedu-tang, Orengedoku-to), a traditional herbal formula, is used for treating inflammation, hypertension, gastritis, liver dysfunction, cerebrovascular diseases, dermatitis and dementia. The objective of this study was to assess the sub-acute toxicity of HHT in Sprague-Dawley (SD) rats, and its effect on the activities of human microsomal cytochrome P450s (CYP450s) and UDP-glucuronosyltransferases (UGTs). Methods: Male and female SD rats were orally administered HHT once daily at doses of 0, 500, 1000 and 2000 mg/kg for 4 weeks. We analyzed mortality, clinical observations, body weight, food consumption, organ weights, urinalysis, hematology, serum biochemistry, and histopathology. The activities of major human CYP450s (CYP1A2, CYP3A4, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and CYP2E1) and UGTs (UGT1A1, UGT1A4, and UGT2B7) were assessed using in vitro fluorescence- and luminescence-based enzyme assays, respectively. Results: No toxicologically significant changes related to the repeated administration of HHT were observed in both male and female SD rats. The no observed adverse effect level (NOAEL) value was more than 2000 mg/kg/day for both sexes. HHT inhibited the activities of human microsomal CYP1A2, CYP2C19, CYP2D6, and CYP2E1, whereas it weakly inhibited the activities of CYP2B6, CYP2C9, CYP3A4, and UGT1A1. In addition, HHT negligibly inhibited the activities of human microsomal UGT1A4 and UGT2B7 with $IC_{50}$ values in excess of $1000{\mu}g/mL$. Conclusions: Our findings indicate that HHT may be safe for repeated administration up to 4 weeks. In addition, these findings provide information on the safety and effectiveness of HHT when co-administered with conventional drugs.

• 대한한의학회지
• /
• 제31권3호
• /
• pp.34-46
• /
• 2010

Objective: This experimental study was performed to examine if Hang-Am-Dan non-boiled water extracts (HAD-N) induce apoptosis in human lung carcinoma NCI-H460 cells in vitro and inhibits the growth of NCI-H460 cell-transplanted solid tumor in vivo. Materials and Methods: We cultured NCI-H460 cell lines and xenografted them to nude mice. The mice were divided into 3 groups, NCI-H460 cell alone, NCI-H460 + 90 mg/kg HAD-N treated group, and NCI-H460 + 180 mg/kg HAD-N treated group, with seven mice per group. HAD-N was orally administrated every day for four weeks. We checked their body weight and tumor weight and volumes two times a week and their absolute organ weight and biochemical blood analysis at the final day by sacrificing them. We also calculated their tumor inhibition rate (IR), mean survival time and percent increase in life span (% ILS). Results: In this study, we observed that all of the HAD-N treated mice got smaller tumors. The more doses of HAD-N used, the less IR showed at the 8th day after starting this experiment. Tumor weight and volume of HAD-N treatment groups also decreased. Mean survival time and percent increase in life span (% ILS) in the high-dose HAD-N treatment groups were higher than those of other groups. The test substances in the blood level UN results showed reduction in the significance in both HAD-N 90 mg/kg and HAD-N 180 mg/kg (p<0.01). The blood level phosphatase results in HAD-N 90 mg/kg group compared to NCI-H460 cell alone group showed a reduction in significance (p<0.05). AST levels HAD-N 180 mg/kg group compared to NCI-H460 cell alone group significance as well (p<0.05). Conclusion: We suggest that the results of the in vivo study showed that HAD-N may have potential as a growth inhibitor of tumor-induced NCI-H460 of nude mice in spite of the shortcomings of this study. More studies to overcome those shortcomings and to find out significant antitumor mechanism will be needed.

• Clinical and Experimental Reproductive Medicine
• /
• 제38권3호
• /
• pp.135-141
• /
• 2011

Objective: Ovarian angiogenesis plays an important role in folliculogenesis. However, little is known about the expression of angiogenic factors during follicular development according to female age. Stromal cell derived factor-$1{\alpha}$ (SDF-$1{\alpha}$) plays a role in granulosa cell survival and embryo quality as an angiogenic chemokine. Leptin is also involved in folliculogenesis and angiogenesis. This study examined expression of SDF-$1{\alpha}$ and leptin, and their effects on the expression of angiogenic factors in the ovary during follicular development according to female age. Methods: Ovaries were collected from C57BL mice of two age groups (6-9 weeks and 24-26 weeks) at 6, 12, 24, and 48 hours after 5 IU pregnant mare's serum gonadotropin (PMSG) injection. The expression of ovarian SDF-$1{\alpha}$ and leptin mRNA was evaluated by RT-PCR. In the organ culture experiment, the ovaries were cultured in transwell permeable supports with Waymouth's medium treated with various doses of SDF-$1{\alpha}$(50-200 ng/mL) or leptin (0.01-1 ${\mu}g$/mL) for 7 days. Then, mRNA expression of vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), and visfatin were examined in the cultured ovaries. Results: Expression of SDF-$1{\alpha}$ and leptin in the ovary was significantly lower in the aged mouse group compared to the young mouse group ($p$ <0.05). Expression of these two factors increased with follicular development after PMSG administration. SDF-$1{\alpha}$ treatment stimulated visfatin expression in a dose-dependent manner, while leptin treatment significantly increased eNOS expression. Conclusion: These results suggest that decrease of ovarian SDF-$1{\alpha}$ and leptin expression may be associated with aging-related reduction of ovarian function. SDF-$1{\alpha}$ and leptin may play a role in follicular development by regulating the expression of angiogenic factors in mouse ovaries.

• 대한약침학회지
• /
• 제18권1호
• /
• pp.63-71
• /
• 2015

Objectives: This study was carried out to analyze the single-dose toxicity of Eun-Bi San pharmacopuncture injected into the muscle of Sprague-Dawley (SD) rats. Methods: All experiments were performed at Biotoxtech, an institution certified to conduct non-clinical studies under the Good Laboratory Practice (GLP) regulations. Six week old SD rats reared by ORIENTBIO were chosen for this pilot study. The reason SD rats were chosen is that they have been widely used in safety tests in the field of medicine, so the results can be easily compared with many other databases. The Eun-Bi San pharmacopuncture was made in a clean room at the Korean Pharmacopuncture Institute (KPI, K-GMP). The constituents of the Eun-Bi San pharmacopuncture are Angelicae gigantis radix, Strychni semen and Glycyrrhizae radix. These were extracted at low temperature and low pressure in an aseptic room at the KPI. Doses of Eun-Bi San pharmacopuncture, 0.25, 0.5 and 1.0 mL, were administered to the experimental groups, and a dose of normal saline solution, 1.0 mL, was administered to the control group. This study was performed under the approval of the Institutional Animal Ethics Committee of Biotoxtech Co., Ltd. Results: No deaths or abnormalities occurred in any of the four groups. No significant changes in weight, hematological parameters or clinical chemistry between the control group and the experimental groups were observed. To determine if abnormalities existed in any organs and tissues, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs or tissues. Conclusion: The results of this study suggest that treatment with Eun-Bi San pharmacopuncture is relatively safe and that its clinical use may be beneficial. Further evaluations and studies on this subject will be needed to provide more concrete evidence in support of these conclusions.

• Radiation Oncology Journal
• /
• 제34권1호
• /
• pp.26-33
• /
• 2016

Purpose: To compare the dose distribution between carotid sparing intensity modulated radiotherapy (IMRT) and opposed lateral field technique (LAFT), and to determine the effects of carotid sparing IMRT in early glottic cancer patients who have risk factors for atherosclerosis. Materials and Methods: Ten early glottic cancer patients were treated with carotid sparing IMRT. For each patient, the conventional LAFT plan was developed for comparison. IMRT and LAFT plans were compared in terms of planning target volume (PTV) coverage, conformity index, homogeneity index, and the doses to planning organ at risk volume (PRV) for carotid arteries, spinal cord and pharyngeal constrictor muscle. Results: Recurrence was not observed in any patients during the follow-up period. $V_{95%}$ for PTV showed no significant difference between IMRT and LAFT plans, while $V_{100%}$ was significantly higher in the IMRT plan (95.5% vs. 94.6%, p = 0.005). The homogeneity index (11.6%) and conformity index (1.4) in the IMRT plan were significantly better than those in the LAFT plans (8.5% and 5.1, respectively) (p = 0.005). The median $V_{5Gy}$ (90.0%), $V_{25Gy}$ (13.5%), and $V_{50Gy}$ (0%) for carotid artery PRV in the IMRT plan were significantly lower than those in the LAFT plan (99.1%, 89.0%, and 77.3%, respectively) (p = 0.005). Conclusion: Our study suggests that carotid sparing IMRT can significantly decrease the dose to carotid arteries compared to LAFT, and it would be considered for early glottic cancer patient with high risk of atherosclerosis.

• 한국방사선학회논문지
• /
• 제7권4호
• /
• pp.259-264
• /
• 2013

전신방사선조사는 소아백혈병의 치료 방법 중 하나인 조혈모세포이식의 전처치로 이용되고 있으며, 현재 조직보상체를 사용하여 치료를 시행하고 있다. 그러나 조직보상체의 조건에 따라 인체 내부 장기에 미치는 영향을 직접 평가하는 것은 어려움이 있다. 이에 본 연구는 수학적 모의피폭체를 사용하여 방사선의 에너지와 선원과 환자와의 거리(source surface distance, SSD), 조직보상체와 환자와의 거리 변화에 따라 인체 장기의 선량을 평가하였다. 그 결과, 표면선량은 에너지 4 MV, SSD 280 cm, 조직보상체와 환자와의 거리 30 cm일 때 5.84 G/min 으로 가장 높은 수치를 나타내었다. 또한 조직보상체와 환자와의 거리가 30 cm 이하였을 때 TBI에서 가장 이상적인 선량분포를 나타냄을 알 수 있었다.