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Anti-amnesic and Antioxidant Effect of Yeongkyekamjotanggayonggolmoryo Aqueous Extracts on Scopolamine-induced Memory Impairment in Mice (Scopolamine 유발 기억력손상 흰 쥐에서 영계감조탕가용골모려(笭桂甘棗湯加龍骨牡蠣)의 인지기능개선과 항산화 효과)

  • Kim, Dae-eok;Han, Da-young;Kim, Sang-ho;Chung, Dae-kyoo
    • Journal of Oriental Neuropsychiatry
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    • v.29 no.3
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    • pp.121-134
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    • 2018
  • Objectives: The purpose of this in vivo study is to observe anti-amnesic effects of Yeongkyekamjotanggayonggolmoryo (YGYM), a novel mixed herbal prescription, Ossis Mastodi and Ostreae Testa added Yeongkyekamjo-tang, on scopolamine induced amnesia in C57BL/6 mice through acetylcholine (ACh) and acetylcholinesterase (AChE) activity, Choline acetyltransferase (ChAT) mRNA expression, and antioxidant effects. Methods: Six groups, total 20 intact or 100 Sco treated mice were used in this study after one week of acclimatization period. Half the animals were used for passive avoidance task tests and hippocampus ACh content, AChE activity, and ChAT mRNA expression were measured. The other half was subjected to an underwater maze test and then the cerebral cortex antioxidant defense system was measured. Results: In the passive avoidance experiment, there was significant decrease in residence time in the bright room and in the underwater maze test, escape latency to escape from the esophagus significantly increased compared with the normal control group. At the final sacrifice, ACh content and ChAT mRNA expression decreased, AChE activity increased, and cerebral cortical MDA increased GSH content, SOD and CAT activity in Sco control mice, as compared to intact vehicle control mice. However, these Sco treatment-related memory loss through AChE activation destroyed the cerebral cortex antioxidant defense system, and was inhibited dose-dependently by 28 days consecutive oral pretreatments of YGYM extracts 500, 250, 125 mg/kg. Conclusions: In the above results, YGYM extract that oral administration of YGYM extracts alleviates the antioxidant defense system, through preservation of ACh mediated by upregulation of ChAT mRNA expression, and increase of AChE inhibition and brain antioxidant defense systems.

Pharmacokinetics of High-dose Methotrexate in Pediatric Patients with Osteosarcoma (소마 골육증 환자에서 고동량 Methotrexate의 Pharmacokinetics)

  • Nam, Taeg-Jong;Park, Gwang-Jun;Shin, Wan-Gyoon
    • Korean Journal of Clinical Pharmacy
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    • v.16 no.1
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    • pp.1-8
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    • 2006
  • Methotrexate(MTX)는 소아 골육종 환자에서 $12g/m^2$의 고용량을 사용하고 있다. 현재, 소아 골육종 환자에서 신기 능에 따른 고용량 MTX의 임상 약동학은 연구되어 있지 않다. 따라서 본 연구에서는 신기능에 따른 MTX 약동학을 이용하여 구내염을 최소화하는 방법을 제시하고자 하였다. 방법: 환자들의 의무기록지를 후향적 방법으로 검토하였다. 한 병원에서 골육종으로 진단받고, 치료 받은 환자들을 대상으로 정상 신기능군과 비정상 신기능군으로 나누었다. 두 군에 MTX 투여 후 혈중 농도를 각각 비교하였고, 최고 혈중농도도 비교하였다. 혈중 농도와 구내염의 관련성, CL, AUC와 구내염의 상관관계를 분석하였다. 각 군의 terminal half-life, CL, Vss의 평균과 mea residence time(MRT)의 평균을 구하였고, 두 군간 각각을 비교하였다 $({\alpha}=0.05)$. 결과: 환자는 6명이었고, 평가 가능한 총 MTX 투여 회수는 34회였다. MTX 투여 후 최고혈중 농도, 24,48 시간의 혈중농도는 통계적으로 유의성 있는 차이가 있었고, 72,96 시간에서의 농도는 두 군간 유의성이 없었다. 각 군에서 혈중농도와 구내염의 상관관계, 그리고 CL, AUC와 구내염의 상관관계는 발견되지 않았다. Vss를 제외한 모든 파라미터들(terminal half-life, CL, MRT)은 통계적으로 유의성 있는 차이가 있었다. 결론: 비정상 신기능 군에서 MTX 투여 시작 후 24, 48 시간에서의 혈중농도가 더 높고, 변동이 심했다. 또한 MTX의 CL는 감소했고, 혈중농도는 증가하였다. 이러한 사실로 MTX 투여 전 후 혈중 크레아티닌이나 또는 크레아티닌 청소율 모니터링이 필요하다는 것을 알 수 있으며, MTX 투여가 끝난 직후 그리고 그 이후 24 시간 간격으로 혈중 농도를 측정해야함을 알 수 있다.

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A Study on the Significance of the Colloidal Radiogold Disappearance Rate as a Simple Clinical Liver Function Test (임상간기능검사법(臨床肝機能檢査法)으로서의 교질형방사성금(膠質形放射性金)의 혈중소실율(血中消失率)의 의의(意義)에 관(關)한 연구(硏究))

  • Hong, Chang-Gi
    • The Korean Journal of Nuclear Medicine
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    • v.3 no.1
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    • pp.1-12
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    • 1969
  • Liver functions in diffuse parenchymal liver disease such as cirrhosis of the liver depend largely on the effective hepatic blood flow rather than on the individual cell functions. Clinical methods of measuring the hepatic blood flow were developed recently by the application of colloidal disappearance rate. In order to correlate the radiogold disappearance rate to conventional biochemical liver function tests, 21 normal subjects and 80 cases of cirrhosis of the liver were studied with both methods. The results are summarized as following: 1. The validity of external counting method to measure the blood disappearance rate of colloidal radiogold was confirmed by in vitro counting of the serial blood samples. 2. The blood disappearance rate of collidal radiogold was essentially the same. as the liver uptake rate of colloidal radiogold in normal and cirrhotic subjects with various degrees of functional disturbance. And it seemed there was no serious extrahepatic removal of the colloidal radiogold. 3. The disappearance rate of colloidal radiogold was not significantly changed by the posture change, but was enhanced by ingestion of 500 ml of water. 4. The disappearance rate of colloidal radiogold was not influenced by single dose of Telepaque, while BSP retention was increased after Telepaque. 5. The mean disappearance half time of colloidal radiogold in normal subjects was $2.49{\pm}0.391$(S.D.) minutes. The mean normal disappearance rate constant (K value) was $0.285{\pm}0.0428$(S.D.)/minute. 6. The colloidal radiogold disappearance half time was abnormally prolonged (over 3.2 min.) in $87.7{\pm}3.68$(S.D.) % of cirrhotic subjects. 7. In patients of liver cirrhosis the blood disappearance rate of colloidal radiogold correlated well to serum albumin and globulin levels and BSP retention which were considered to reflect functions of hepatic parenchymal cells. There was, however, no correlation between colloidal disappearance rate and thymol turbidity test, serum glutamic pyruvic transaminase, and serm alkaline phosphatase activities. The latters were considered to be associated with the activity of liver disease.

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Cell-Based IL-15:IL-15Rα Secreting Vaccine as an Effective Therapy for CT26 Colon Cancer in Mice

  • Thi, Van Anh Do;Jeon, Hyung Min;Park, Sang Min;Lee, Hayyoung;Kim, Young Sang
    • Molecules and Cells
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    • v.42 no.12
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    • pp.869-883
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    • 2019
  • Interleukin (IL)-15 is an essential immune-modulator with high potential for use in cancer treatment. Natural IL-15 has a low biological potency because of its short half-life and difficulties in mass-production. IL-15Rα, a member of the IL-15 receptor complex, is famous for its high affinity to IL-15 and its ability to lengthen the half-life of IL-15. We have double-transfected IL-15 and its truncated receptor IL-15Rα into CT26 colon cancer cells to target them for intracellular assembly. The secreted IL-15:IL-15Rα complexes were confirmed in ELISA and Co-IP experiments. IL-15:IL-15Rα secreting clones showed a higher anti-tumor effect than IL-15 secreting clones. Furthermore, we also evaluated the vaccine and therapeutic efficacy of the whole cancer-cell vaccine using mitomycin C (MMC)-treated IL-15:IL-15Rα secreting CT26 clones. Three sets of experiments were evaluated; (1) therapeutics, (2) vaccination, and (3) long-term protection. Wild-type CT26-bearing mice treated with a single dose of MMC-inactivated secreted IL-15:IL-15Rα clones prolonged survival compared to the control group. Survival of MMC-inactivated IL-15:IL-15Rα clone-vaccinated mice (without any further adjuvant) exceeded up to 100%. This protection effect even lasted for at least three months after the immunization. Secreted IL-15:IL-15Rα clones challenging trigger anti-tumor response via CD4+ T, CD8+ T, and natural killer (NK) cell-dependent cytotoxicity. Our result suggested that cell-based vaccine secreting IL-15:IL-15Rα, may offer the new tools for immunotherapy to treat cancer.

Pharmacokinetics of a sustained-release bovine somatotropin in lactating cows

  • Han, Seong-kyu;Park, Jin-bong;Kim, Doo;Park, Sang-kyoon;Lee, Ho-sung;Kim, Seong-nam;Chang, Byoung-sun;Ryu, Pan-dong
    • Korean Journal of Veterinary Research
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    • v.39 no.2
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    • pp.267-275
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    • 1999
  • Bovine somatotropin is known to improve the growth rate and lactation in cattle. In this study, we examined the concentration-time profiles of a sustained-release formulation of bovine somatotropin (BST) and insulin-like growth factor-1 (IGF-1) in plasma and milk in cows. In addition, the possible effect of co-administrated vitamin ADE complex on the pharmacokinetic parameters of BST and IGF-1 was evaluated. 1. Plasma BST and IGF-1 levels reached the peak at 12~24 and 48 hours after the administration of BST, and plasma half-lives ranged 100 to 137 and 201 to 310 hours, respectively. To 8th day after administration, BST and IGF-1 levels in milk were not significantly different from the control levels. 2. Plasma BST levels showed cyclic pattern with high concentrations in early stage after each injection and following gradual declining during repeated administrations at 2 week intervals, while plasma IGF-1 levels in treated animals did not show such a cyclic pattern, but remained higher than the control levels. 3. Milk BST and IGF-1 levels during repeated treatments were not significantly different from the control levels. 4. Co-administration of vitamin ADE complex yielded slightly increased AUC of plasma BST for high dose group, but such effect was not evident in the IGF-1 levels. Co-administration of ADE complex tended to increase plasma BST levels and decrease the elimination half-life of IGF-1. 5. These results suggest that the BST formulation tested is one of the ideal sustained-release formulation for long term use in dairy industry. As for the co-administration of vitamin ADE complex, the benefit of co-administration with BST is needed to be further evaluated.

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Residues of Diazinon in Growing Chinese cabbage: A study Under Greenhouse Conditions

  • Khay, Sathya;El-Aty, A.M. Abd;Lim, Kye-Taek;Shim, Jae-Han
    • Korean Journal of Environmental Agriculture
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    • v.25 no.2
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    • pp.174-179
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    • 2006
  • Chinese cabbage, Braccica campestris has long been consumed as a staple food for Koreans in various forms of fresh, salted, and fermented Kimchi. Cultivation of the crop under greenhouse has become a general practices to fulfill its off-seasonal consumer's demand. However, agricultural practices of the crop have always accompanied with heavy applications of pesticides caused by severe outbreaks of diseases and pose under warm and humid circumferences. Since dissipation patterns of pesticide residues in/on the crop under greenhouse conditions ate quite different from those in the open-air, changes of diazinon, O,O-diethyl O-2-isopropyl-6-methylpyrimidin-4-yl phosphornthioate, in/on the Chinese cabbage applied by foliar spraying under greenhouse were studied. Diazinon 34% EC was applied with dilution of recommended and double dose to the crop. The shoots of crop were harvested immediately after this application and at regular intervals over a 10-day. After sample preparations, the diazinon residue was analyzed using gas chromatography equipped with electron capture detector (GC/ECD). Initially deposited amount of the chemical in/on the crop right after applications with recommended and double doses were 8.3 and 15.2 mg/kg, respectively. The residue levels after 10 days of application were 0.03 and 0.09 mg/kg with 1.3 and 1.5 days of half-life in/on the crop, respectively. In consequent 10 days of pre-harvest interval (PHI) for diazinon EC formulation in/on Chinese cabbage under greenhouse condition was fulfill maximum residue level set by Korea Food and Drug Administration (KFDA, 0.1 mg/kg).

Pharmacokinetic Characterization of Nano-emulsion Vitamin A, D and E (LaVita) in Rats

  • Lee, Young-Ju;Kwon, Min;Kim, Tae-Hwan;Kim, Kyun;Jeong, Sang-Hee;Chang, Hee-Ra
    • Korean Journal of Environmental Agriculture
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    • v.30 no.2
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    • pp.196-201
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    • 2011
  • BACKGROUND: Bioavailability enhancement by solubilization of lipophilic drugs in nano-emulsion has been reported and it may be useful in pharmaceutical and nutraceutical products. This study was performed to compare in vivo bioavailability of nano-emulsion formulation with that of the general product as control. METHODS AND RESULTS: The pharmacokinetics assessment of Vitamin A, D and E complex of nanoemulsion formulation (LaVita), in comparison to the general product, was performed in the male rat plasma by a single oral dose at 20 mL/kg body weight (n=3/group). For nano-emulsion formulation (LaVita), $C_{max}$ of vitamin A and E in plasma were much higher and the area under the curve (AUC) of vitamin A, D and E were 14-63% higher, and the half-life of vitamin E was 2-fold longer than the general product. According to statistical analysis, each $C_{max}$ of vitamin A, D & E was significantly higher (p<0.01, 0.05 and 0.01, respectively) than that of general product. Half-life of vitamin A was significantly higher (p<0.01) and AUC of vitamin A and D were also significantly higher than the general product. CONCLUSION(s): Considering significant increment of $C_{max}$ and AUC, LaVita made of nano-emulsion could be more effective the absorption rate and extent for bioavailability of vitamin A, D & E than those of general product.

HPLC Determination and Pharmacokinetic Profile of Procainamidein Korean Subjects (프로카인아미드의 HPLC 분석법 및 한국인에서의 약동학적 특성)

  • Bae Jung-Woo;Kim Hyun-Kyung;Yang Sang-In;Kim Ji-Hong;Kim Kyung-Hye;Jang Choon-Gon;Park Young-Seo;Sohn Uy-Dong;Lee Seok-Yong
    • YAKHAK HOEJI
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    • v.49 no.3
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    • pp.193-197
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    • 2005
  • Procainamide is the drug of second choice (after lidocaine) in most coronary care units for the treatment of sustained ventricular arrhythmias associated with acute myocardial infarction. The purpose of this study was to develop the efficient assay method of procainamide in human plasma and to assess the pharmacokinetic profile of procainamide in healthy Korean volunteers. The pharmacokinetics of procainamide administered orally was evaluated after a dose of 250 mg. Procainamide in plasma was assayed using a specific HPLC method with UV absorbance at 275 nm. AUC was $4.58{\pm}0.90 {\mu}g/ml-hr$, $C_{max}\;1.34{\pm}0.39{\mu}g/ml$, $T_{max}\;1.06{\pm}0.34 hr$ and half-life $3.07\pm0.34 hr$. $T_{max}$ was slightly shorter than that in Caucasian (1-2 hr), whereas the half-life was similar to that in Caucasian (2.5-4.1 hr).

HPLC Determination and Pharmacokinetic Profile of Warfarin in Korean Subjects (와파린의 HPLC 분석법 및 한국인에서의 약동학적 특징)

  • Bae, Jung-Woo;Kim, Hyun-Kyung;Yang, Sang-In;Kim, Ji-Hong;Kim, Kyung-Hye;Jang, Choon-Gon;Park, Young-Seo;Sohn, Uy-Dong
    • YAKHAK HOEJI
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    • v.49 no.2
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    • pp.134-139
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    • 2005
  • Warfarin is a widely used oral anticoagulant agent used to treat thromboembolic disease. The purpose of this study was to develop the efficient assay method of warfarin sodium i n human plasma and to assess the pharmacokinetic profile of the warfarin in healthy Korean volunteers. The pharmacokinetics of warfarin administered orally was evaluated after a dose of 10 mg. Warfarin in plasma was assayed using a specific HPLC method with UV absorbance at 304 nm. AUC was 46.33${\pm}9.95{\mu}g/ml.hr$, $C_{max}$ $1.22{\pm}0.22{\mu}g/ml, $T_{max}$$2.50{\pm}1.41$ hr and half-life $43.49{\pm}4.33$ hr. $T_{max}$ was slightly shorter than that in Caucasian (3~9 hr), whereas the half-life was longer than that in Caucasian (10~45 hr, mean: 36 hr). These results suggest that warfarin may have a longer duration in Korean than in Caucasian.

Aucklandiae Radix Ameliorates Scopolamine-induced Memory Impairment in Mice (Scopolamine 유발 기억력 손상 마우스 모델에서 목향(木香)의 기억력 개선 및 항산화 효과)

  • Park, Na-eun;Han, Da-young;Kim, Sang-ho;Chung, Dae-kyoo
    • Journal of Oriental Neuropsychiatry
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    • v.28 no.2
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    • pp.123-136
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    • 2017
  • Objectives: The objective of this study is to investigate the anti-amnesic effects of AR, Aucklandiae Radix, ground powder on scopolamine (Sco)-induced memory impairment in mice (C57BL/6) through its favorable acetylcholine (ACh) and acetylcholinesterase (AChE) activity, Choline acetyltransferase (ChAT) mRNA expression, and antioxidant effect. Methods: Six groups, a total of 20 intact or 100 Sco treated mice, were selected based on their body weights and were used in this study. Half of the mice in each group were used for the passive avoidance task test and the measurements of hippocampus ACh content, AChE activity and ChAT mRNA expression. The remaining half of the mice in each group were used for the Morris water maze test and cerebral antioxidant defense system measurement. Results: Marked decreases in step-through latency times in the passive avoidance task test and increases in escape latency times in the Morris water maze test were observed with decreases in the hippocampus ACh content and ChAT mRNA expression, and increases in the hippocampal AChE activities, as a result of Sco intraperitoneal treatment, in the present study. In addition, destruction of the cerebral cortex antioxidant defense systems was observed in Sco control mice as compared with intact vehicle control mice. However, 28 days of continuous oral pre-treatment with AR ground powder at doses of 400, 200 and 100 mg/kg markedly and dose-dependently inhibited the Sco treatment-related amnesia. Conclusions: The results prove that oral administration of AR ground powder reduces Sco-induced memory impairment. This is because it can preserve ACh, related to ChAT mRNA expression, cause AChE inhibition, and activate the cerebral antioxidant defense system.