• 대한한방내과학회지
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• 제29권1호
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• pp.130-148
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• 2008

Objective : This study was designed to investigate the effect of the water extract of Gamisamgibopae-tang(GMSGBPT), an oriental herbal formulation, on the growth of NCI-H460 and A549 human non-small-cell lung cancer cell lines. Methods : Cytotoxicity and cell morphology were evaluated by MTT assay and inverted microscope, respectively. Apoptosis was detected using agarose gel electrophoresis and flow cytometer. The expression levels of mRNAs and proteins of target genes were determined by RT-PCR and western blot analyses, respectively Result and Conclusion : We found that exposure of A549 cells to GMSGBPT resulted in the growth inhibition in a dose-dependent manner as measured by MTT assay, but GMSGBPTdid not affect the growth of NCI-H460 cells. The anti-proliferative effect of GMSGBPT treatment in A549 cells was associated with morphological changes, formation of apoptotic bodies and DNA fragmentation, and flow cytometry analysis confirmed that GMSGBPT treatment increased the populations of apoptotic-sub G1 phase. Growth inhibition and apoptotic cell death by GMSGBPT were connected with a up-regulation of cyclin-dependent kinase inhibitor p21 (WAF1/CIP1) mRNA and protein in a tumor suppressor p53-independent fashion. However GMSGBPT treatment did not affect other growth regulation-related genes such as early growth response-1 (Egr-1), nonsteroidal anti-inflammatory drug (NSAID)-activated gene-1 (NAG-1), inducible nitric oxide synthase (iNOS), cyclooxygenases (COXs), telomere-regulatory factors in A549 orNCI-H460 cells. Taken together, these findings partially provide novel insights into the possible molecular mechanism of the anti-cancer activity of GMSGBPT.

• 동의신경정신과학회지
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• 제18권2호
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• pp.57-74
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• 2007

Objective : The purpose of this study was to investigate the anti-obesity and anti-hyperlipidemic Effects of Taeyeumjowee-tang and its modified prescription on the animal model of obesity and hyperlipidemia induced high-fat diet. Method : 1) The extracts of Taeyeumjowee-tang (TJT) and its modified prescription, Taeyeumjoweetang gagam-bang (TJGB) were evaluated for its inhibitory effects on obesity. 2) The body weight and feed weight were determined in the pre-treated and post-treated mice and the lipid profiles in the serum were analyzed in order to evaluate the anti-hyperlipidemia action of the extracts. 3) The effect of each extract was investigated for the influences on monoamine oxidase activity and HMG-CoA reductase activity. Results 1. TJT and TJGB extracts dose-dependently reduced the body weight and feed intake in normal mice. The effect of TJGB extract was better than that of TJT extract. 2. TJGB extract diminished the body weight increase and reduced the feed intake in the pre-treatment or post-treatment of the extract 3. TJGB extract decreased the amount of total cholesterol slightly and triglyceride potently after the pre-treatment or post-treatment, but HDL cholesterol exhibited no remarkable change compared with control. 4. TJGB extract weakly potentiated the monoamine oxidase activity, but its effect was better than that of TJT extract. 5. TJGB extract weakly inhibited the HMG-CoA reductase activity, but its effect was better than that of TJT extract. Conclusion : Taeyeumjowee-tang and its modified prescription can clinically be useful as anti-obesity drug and also for the improvement of hyperlipidemia.

• Biomolecules & Therapeutics
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• 제6권3호
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• pp.289-295
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• 1998

The bioequivalence of two nilvadipine products was evaluated in 16 normal male volunteers (age 22-32 yr, body weight 57-80 kg) following sidle oral dose. Test product was Overca $l_{R}$ tablet (Choong-Wae Pharm. Corp., Korea) and reference product was Nivadi $l_{R}$ tablet (Hyundai Pharm. Corp., Korea). Both products contain 4 mg of nilvadipine. One tablet of the test or the reference product was administered to the volunteers, respectively, by randomized two period cross-over study (2$\times$2 Latin square method). The determination of nilvadipine was accomplished using a validated capillary column GC with electron-capture detection. As a result of the assay validation, the quantiflcation of nilvadipine in human plasma by this technique was possible down to 0.5 ng/ml using 1 ml of plasma. Absolute overall recovery from five replicate analyses of nilvadipine-spiked sample were 88.4$\pm$ 10.24% (mean$\pm$ 5.D.) for human plasma of 10 ng/ml. The coefficients of variation (C.V.) were less than 20% and the actual concentration of nilvadipine measured by GC ranged from 80 to 99% in all plasma. Average drug concentrations at each sampling time and pharmacokinetic parameters calculated were not significantly different between two products (p>0.05); the area under the curve from time zero to 8 hr (AUCo-$_{8 hr}$) (22.8$\pm$5.90 vs 22.2$\pm$6.10 ng . hr/ml), maximum plasma concentration ( $C_{max}$) (10.0$\pm$2.85 vs 9.3$\pm$3.28 ng/ml) and time to reach maximum plasma concentration ( $T_{max}$) (1.2$\pm$0.31 vs 1.3 $\pm$0.47 hr). The differences of mean AU $Co_{8hr}$ $C_{max}$, and $T_{max}$ between the two products (2.25, 7.65, and 10.30%, respectively) were less than 20%. The power (1-$\beta$) and treaeent difference (7) for AU $Co_{8hr}$, and $C_{max}$ were more than 0.8 and less than 0.2, respectively. Although the power for Tmax was under 0.8, Tm\ulcorner of the two products was not significantly different from each other (p>0. 05). These results suggest that the bioavailability of Overeat tablet is not significantly different from that of Nivadil tablet. Therefore, two products are bioequivalent based on the current results.sults.lts.lts.lts.

• 대한미생물학회지
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• 제13권1호
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• pp.55-62
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• 1978

항암제(抗癌劑)로 잘 알려진 cyclophosphamide(CY)를 성숙(成熟)한 마우스에 체중(體重) kg당(當) 300mg을 복강내(腹腔內)에 투여(投與)하여 CY가 체중(體重), 비장중량(脾臟重量) 및 말초임파조직(末梢淋巴組織)에 미치는 영향(影響)을 실험(實驗)하였다. CY는 마우스의 체중(體重)을 약간(若干) 감소(減少)시켰으나 체중(體重)은 곧 회복(回復)되었다. CY가 비장중량(脾臟重量)에 미치는 영향(影響)은 현저(顯著)하였는데 초기(初期)엔 비장중량(脾臟重量)은 감소(減少)되었으나 곧 회복(回復)되고 그 후(後) 정상(正常)보다 더 증가(增加)되었는데 그 증가(增加)는 CY투여(投與) 20일(日)이 지나서야 정상(正常)으로 되돌아왔다. 비장(脾臟) 및 임파절(淋巴節)의 조직학적(組織學的) 형태(形態)에 미치는 CY의 영향(影響)은 다양(多樣)하였다. 즉(卽), 흉선의존세포(胸線依存細胞)가 위치(位置)하는 비장(脾臟)의 periarterial lymphatic sheath와 임파절(淋巴節)의 paracortex는 골수유래세포(骨髓由來細胞)가 위치(位置)하는 follicles보다 1일(日) 내지(乃至) 2일(日) 늦게 소실(消失)되었으며 비장(脾臟)의 비대(肥大)가 최고(最高)에 달(達죠)하였을때 비장(脾臟)이나 임파절(淋巴節)의 구조(構造)는 동일(同一)한 임파양세포(淋巴樣細胞)로 구성(構成)된 interstitial tissue로 대치(代置)되어 있었다. 비장(脾臟)의 중량(重量)이 정상화(正常化)되어감에 따라 비장(脾臟)이나 임파절(淋巴節)의 구조(構造)가 정상화(正常化) 되어갔다. 이와 같은 본(本) 실험(實驗)의 소견(所見)은 CY는 골수유래세포(骨髓由來細胞) 뿐만 아니라 흉선의존세포(胸線依存細胞)에도 영향(影響)을 미친다고 사료(思料)된다. 저자(著者)들은 전보(前報)에서 CY에 의(依)한 지연성과민반응(遲延性過敏反應)의 항진(亢進)은 suppressor T cell의 제거(除去)에 기인(基因)한 것이라고 시사(示唆)하였는데 본(本) 실험결과(實驗結果)는 이를 뒷받침해준다고 사료(思料)되었다.

• 동의생리병리학회지
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• 제22권2호
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• pp.415-421
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• 2008

Pro-inflammatory mediators, such as prostaglandin $E_2$ (PGE2), nitric oxide (NO), and cyclooxygenases-2 (COX-2), play pivotal roles in normal as well as transformed cells. Previous studies have shown that Euphorbiae humifusae Wind exhibits anti-proliferative and antioxidant activities. However, the it's anti-inflammatory properties are unclear. In this study, we examine the effects of water extract of E. humifusae (WEEH) on the expression of COX-2 and the production of $PGE_2$ in human lymphatic U937 cells. Treatment of phorbol 12-myristate-13-acetate (PMA) significantly induced COX-2 expression and $PGE_2$ production in U937 cells. However, pretreatment WEEH markedly inhibited the PMA-induced COX-2 expression and $PGE_2$ production in a dose-dependent manner. Moreover, WEEH prevented the elevated early growth response gene-1 (Egr-1) expression and nuclear factor-kappaB ($NF{-\kappa}B\; p65$) nuclear translocation stimulated by PMA treatment. Taken together, the present data indicate that WEEH exhibits anti-inflammatory properties by suppressing the transcription of pro-inflammatory cytokine genes through the $NF{-\kappa}B$ and Egr-1 signaling pathway.

• Toxicological Research
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• 제29권1호
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• pp.21-25
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• 2013

The selective targeting of an integrin ${\alpha}_v{\beta}_3$ receptor using radioligands may enable the assessment of angiogenesis and integrin ${\alpha}_v{\beta}_3$ receptor status in tumors. The aim of this research was to label a peptidomimetic integrin ${\alpha}_v{\beta}_3$ antagonist (PIA) with $^{99m}Tc(CO)_3$ and to test its receptor targeting properties in nude mice bearing receptor-positive tumors. PIA was reacted with tris-succinimidyl aminotriacetate (TSAT) (20 mM) as a PIA per TSAT. The product, PIA-aminodiacetic acid (ADA), was radiolabeled with $[^{99m}Tc(CO)_3(H_2O)_3]^{+1}$, and purified sequentially on a Sep-Pak C-18 cartridge followed by a Sep-Pak QMA anion exchange cartridge. Using gradient C-18 reverse-phase HPLC, the radiochemical purity of $^{99m}Tc(CO)_3$-ADA-PIA (retention time, 10.5 min) was confirmed to be > 95%. Biodistribution analysis was performed in nude mice (n = 5 per time point) bearing receptor-positive M21 human melanoma xenografts. The mice were administered $^{99m}Tc(CO)_3$-ADA-PIA intravenously. The animals were euthanized at 0.33, 1, and 2 hr after injection for the biodistribution study. A separate group of mice were also co-injected with 200 ${\mu}g$ of PIA and euthanized at 1 hr to quantify tumor uptake. $^{99m}Tc(CO)_3$-ADA-PIA was stable in phosphate buffer for 21 hr, but at 3 and 6 hr, 7.9 and 11.5% of the radioactivity was lost as histidine, respectively. In tumor bearing mice, $^{99m}Tc(CO)_3$-ADA-PIA accumulated rapidly in a receptor-positive tumor with a peak uptake at 20 min, and rapid clearance from blood occurring primarily through the hepatobiliary system. At 20 min, the tumor-to-blood ratio was 1.8. At 1 hr, the tumor uptake was 0.47% injected dose (ID)/g, but decreased to 0.12% ID/g when co-injected with an excess amount of PIA, indicating that accumulation was receptor mediated. These results demonstrate successful $^{99m}TC$ labeling of a peptidomimetic integrin antagonist that accumulated in a tumor via receptor-specific binding. However, tumor uptake was very low because of low blood concentrations that likely resulted from rapid uptake of the agent into the hepatobiliary system. This study suggests that for $^{99m}Tc(CO)_3$-ADA-PIA to be useful as a tumor detection agent, it will be necessary to improve receptor binding affinity and increase the hydrophilicity of the product to minimize rapid hepatobiliary uptake.

• 대한수의학회지
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• 제36권1호
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• pp.57-63
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• 1996

Dihydrofolate reductase(DHFR) 억제제는 혈중활성엽산유도체의 농도저하를 초래하는데 이에 대한 기전을 밝히고자 DHFR 억제제의 대표적 약물로서 항암치료에 널리 사용되고 있는 methotrexate를 0.3 및 10mg/kg의 용량으로 랫드에 정맥주사한 후 활성엽산유도체의 담즙배설동태를 검토하였다. 임상적용 용량을 상회하는 용량임에도 불구하고 methotrexate에 의한 환원형엽산유도체의 담즙배설은 유의적 감소를 나타내지 않았다. 이러한 결과는 methotrexate에 의한 엽산유도체의 혈중농도저하가 활성엽산유도체의 담즙배설저하에 직접 관련되지 않는 것을 나타낸다. 따라서 장간순환계가 체내 엽산대사 및 항상성 유지에 중심기구임을 고려해 볼 때 DHFR 억제제에 의한 활성엽산유도체의 혈중농도저하는 담즙배설의 변화에 의한 것 보다는 소화관에 배설된 후 재흡수의 저하에 의해 초래될 가능성이 높은 것으로 사료된다.

• 대한지역사회영양학회지
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• 제23권4호
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• pp.341-351
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• 2018

Objectives: Use of dietary supplements containing vitamins and minerals is growing in Korean adults, especially in pregnant and lactating women. Vitamin and mineral supplements are available in different composition and in a wide range of contents. The purposes of the study were to examine nutrient composition and content of vitamin and mineral supplements for pregnant and lactating women and assess their appropriateness as dietary supplements. Methods: Information on the name, manufacturer, nutrient composition, and usage of vitamin and mineral supplements for pregnant and lactating women were obtained from the homepage of the Food Safety Information Portal managed by the Ministry of Food and Drug Safety, and Korean Index of Medical Specialties. A total of 264 products were identified. Results: Among 264 products, 26.1% were single nutrient products, and 73.9% were multinutrient products. The most commonly included nutrient was iron (70.1%), folic acid (66.3%), vitamin $B_{12}$ (45.8%), vitamin C (38.6%), and vitamin $B_6$ (38.6%). Although more than 50% of products contained nutrients less than 150% of Recommended Nutrient Intakes or Adequate Intakes for daily use, some products contained inappropriately high amounts of nutrients. When a maximum daily dose of supplements was taken as described on the label, iron in 73 products (39.5%), folic acid in 14 products (8.0%) were likely to be consumed in amounts greater than Tolerable Upper Intake Levels. Most products were assessed as inappropriate for pregnant women due to the possibility of excessive intake of vitamins or minerals when compared with Dietary Reference Intakes. Conclusions: Pregnant and lactating women need to carefully select dietary supplements containing adequate amounts of vitamins and minerals. Nutritionists should provide guidelines regarding selection of appropriate vitamin and mineral supplements for pregnant and lactating women.

• 대한두경부종양학회지
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• 제25권1호
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• pp.3-7
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• 2009

Background and Objectives : Panax ginseng C.A. Meyer is a medical plant that has been widely utilized as a tonic and nutritional agent since ancient times in Korea. Ginseng has anti-metastatic property of cancer and immunomodulating activity. The novel acidic polysaccharide compound(MB40) was isolated from the leaves of Panax ginseng C.A. Meyer. To determine immunomodulating activities of MB40, we evaluate anti-cancer and anti-metastatic effects of MB40 in tumor bearing immune competent mice. Material and Methods : C3H mice were divided into three equal groups(Cisplatin treatment group, MB40 treat-ment group, Cisplatin and MB40 treatment group) and were transplanted SCC(Squamous Cell Carcinoma) cells(2${\times}$106) to the lateral side of abdomen. From day 4 after transplantation, MB40 was administrated at dose of 10mg/kg, respectively, every other day by intratumoral injection. Cisplatin was systemically administrated at doses of 1mg/kg, respectively, every week by intraperitoneal injection. Results : 5 days after administration, tumors can be palpated in every mice group. After 13 days of administration, the mice group to which MB40 were administrated exhibited reduction in tumor size respectively, compared to cisplatin group. Overall status of mice such as body weight and activity were superior in MB40 group than cisplatin group. Conclusion : The result of this study indicates MB40 may have significant therapeutic effect and decreases complications induced by systemic chemotheraphy. MB40 may be developed as a novel and potent immunotropics to improve the cell immune system and anti-cancer drug for the treatment of cancer patients in head and neck squamous cell carcinoma.

• 한국수정란이식학회지
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• 제24권1호
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• pp.47-55
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• 2009

This study was performed to investigate the possibility of repeated superovulation treatment at interval from 27 days to 41 days in Hanwoo cattle and to compare with superovulation effect between doses of FSH 200 mg and FSH 400 mg. Different doses of FSH (200 mg or 400 mg) were injected at Day 8 after controlled internal drug release (CIDR) treatment for superovulation of Hanwoo donors following CIDR treatment (Day 8 after the estrus). Superovulation was repeated four times for one donor and number of corpus luteum (CL), number of embryos, number of transferable embryos and pregnancy rate after embryo transfer (ET) were investigated. 5 cows were used for each FSH treatment (10 cows in total). Average number of CL were $10.16{\pm}3.85$ and $11.56{\pm}2.35$ for the donors treated with FSH 200mg and FSH 400mg, respectively. Average number of embryos collected were $8.85{\pm}4.05$ and $8.30{\pm}1.73$ for the donors treated with FSH 200 mg and FSH 400 mg, respectively. Average number of transferable embryos were $5.48{\pm}2.45$ and $4.58{\pm}2.23$ for the donors treated with FSH 200 mg and FSH 400 mg, respectively. The pregnancy rate following ET with embryos collected from 200 mg FSH treated donors and 400 mg FSH treated donors were 61.9% and 53.8% respectively. The numbers of embryos tended to be decreased as the numbers of repeat of superovulation were elapsed. These results indicated that superovulation treatment by about a month to Hanwoo donors is usable and 200 mg of FSH is preferable for simple FSH treatment following CIDR treatment.