• Title/Summary/Keyword: Multiple-dose

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Bioequivalence Study of Toriem® Tablet to Motilium-M® Tablet (Domperidone Maleate 12.72 mg) Evaluated by Liquid Chromatography/Tandem Mass Spectrometry

  • Ryu, Ju-Hee;Choi, Sang-Jun;Lee, Myung-Jae;Lee, Jin-Sung;Kang, Jong-Min;Tak, Sung-Kwon;Seo, Ji-Hyung;Lee, Kyung-Tae
    • Journal of Pharmaceutical Investigation
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    • v.39 no.1
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    • pp.65-71
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    • 2009
  • The aim of the present study was to evaluate the bioequivalence of two domperidone maleate tablets, Motilium-$M^{(R)}$ Tablet (Janssen Korea Ltd., reference product) and $Toriem^{(R)}$ Tablet (Daewon Pharm. Co., Ltd., test product). Domperidone was extracted by liquid-liquid extraction using tert-butyl methyl ether and separated in less than 3 min on $C_{18}$ reverse-phase column using an isocratic elution. A tandem mass spectrometer, as detector, was used for quantitative analysis in positive mode by a multiple reaction monitoring mode to monitor the m/z $426.1{\rightarrow}119.1$ and the m/z $837.4{\rightarrow}158.2$ transitions for domperidone and the internal standard (roxithromycin), respectively. Calibration curves, from $0.05{\sim}50$ ng/mL of domperidone, showed correlation coefficients (r) higher than 0.9941. Intra day and inter day precision (C.V. %) for quality control were ranged from 10.04 to 16.09% and from 10.87 to 18.69%, respectively. The lower limit of quantification (LLOQ) of domperidone was 0.05 ng/mL. The method described is precise and sensitive and has been successfully applied to the study of bioequivalence of domperidone in 24 healthy Korean volunteers. Twenty-four healthy male Korean volunteers received a single dose of each medicine ($2{\times}12.72\;mg$ domperidone maleate) in a $2{\times}2$ crossover study. There was a one-week washout period between the doses. Plasma concentrations of domperidone were monitored for over a period of 24 hr after the administration. $AUC_{0-t}$ (the area under the plasma concentration-time curve) was calculated by the linear trapezoidal rule. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma concentration-time data. The 90% confidence intervals for the log transformed data were within acceptable range of log 0.8 to log 1.25 (e.g., $log\;0.92{\sim}log\;1.05$ for $AUC_{0-t}$, $log\;0.81{\sim}log\;1.05$ for $C_{max}$). The major parameters, $AUC_{0-t}$ and $C_{max}$ met the criteria of KFDA for bioequivalence indicating that $Toriem^{(R)}$ tablet is bioequivalent to Motilium-$M^{(R)}$ tablet.

Usability of 2D/2D Match for Image Guided Radiotherapy (IGRT) of Prostate Cancer with Fiducial Markers (전립선 암 환자의 영상유도 방사선 치료 시 Fiducial Marker를 이용한 2D/2D Match의 유용성에 대한 연구)

  • Bae, Sun-Myung;Yang, Oh-Nam;Song, Heung-Kwon;Back, Geum-Mun
    • The Journal of Korean Society for Radiation Therapy
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    • v.22 no.1
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    • pp.19-24
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    • 2010
  • Purpose: To study the efficacy of marker match with using kilovoltage (KV) X-ray among multiple image guidance that referring tree fiducial marker in radiation therapy for prostate cancer patients. Materials and Methods: KV two-dimantional images (anterior-posterior, right-left) and cone-beam CT volumetric images were acquired after setup for patients with three fiducial markers. Compare the position of the fiducial marker of reference plan computed tomography (CT) and of KV, CBCT images; then decide the shift score of X, Y, and Z. This study executed 5 times on 10 patients and analyzed the shift value. Results: In the radiation therapy using fiducial marker, The function of marker match showed the same direction tendency as the CBCT, and showed X, Y, Z difference of about 0.6, 0.7, and 0.8 (unit: mm). Conclusion: Comparing to this, the result of shift value using 2D marker match showed less than 1.0 mm difference. The function of marker match is considered more useful in time-wise and effective dose rather than CBCT. Therefore, Both methods are used to treat patients for prostate cancer.

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Reusable Multi-story 3D Animation (재구성이 가능한 멀티스토리 3D 애니메이션)

  • Kim, Sungrae;Kim, Ho Sung;Tak, Ji-young;Park, Ji-en;Lim, Sun-hyuk;Kim, Soosanna;Lee, Kyu-seon;Lee, Ji-hyun
    • Proceedings of the Korea Contents Association Conference
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    • 2007.11a
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    • pp.238-242
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    • 2007
  • The existent UCC sites display only finalized contents by publisher. It dose not provide any platform for resources of UCC that public users could reorganize. This paper has developed a platform to be able to produce reusable content using the scenes of the contents and produced a 3D animation with multiple story. It is necessary for user to search the provided contents for easy reorganization of the contents. The scene is classified by the description and information of the scene for handy search. It is obscure for a movie clip to be represent with only one word. Therefore, the proposed platform provides the search technique with a overlapping choice for the specific categories that include most of elements for the scene. Then the user can choose a specific range of the selected movie clip, make a new story with reorganizing the order, and put a caption or BGM on the movie clip. The complete movie clip has the search preferences as a category, new clips, and top favorites. With the Multi-Story line concept, we made a 3D animation about episodes of thermal dolls in the Doll World. This attempt will come to the new marketing way for a field of the visual media like as Music Video, Drama, Feature Film, Commercial Film.

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Effects of Multiple Stress Factors Including Iron Supply on Cell Growth and Lipid Accumulation in Marine Microalga Dunaliella tertiolecta (해양 미세조류 Dunaliella tertiolecta에서 철 공급을 포함한 다중스트레스 인자가 세포성장 및 지질생산에 미치는 영향)

  • Rizwan, Muhammad;Mujtaba, Ghulam;Lee, Kisay
    • Applied Chemistry for Engineering
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    • v.28 no.3
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    • pp.306-312
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    • 2017
  • Changes in the cell growth and lipid accumulation of marine microalga Dunaliella tertiolecta were investigated in response to the combination of different stress factors including the variation of iron supply as a primary stress factor and different options in light irradiation and $CO_2$ supply as a secondary stress factor. High or limited Fe conditions could act as a stress for lipid synthesis. As a secondary stress factor, non-$CO_2$ condition was good for lipid accumulation, but the overall cell growth was sacrificed significantly after a long-time cultivation. Dark condition as a secondary stress factor also favored lipid accumulation and the extent of cell density reduction at the early period in the dark was small compared to other stress conditions. The two-stage cultivation strategy was necessary to maximize lipid production because tendencies of the cell growth and lipid content were not identical under the chosen stress condition. The first stage was for preparing a high cell density under the normal growth-favoring condition and the second stage was the stress condition to induce lipid accumulation in a short time. The short-term (12 h) incubation under the 5X Fe (3.25 mg/L) and dark conditions resulted in the best lipid productivity of 1.44 g/L/d providing 2 g/L inoculum at the second stage.

An Edible Gintonin Preparation from Ginseng

  • Choi, Sun-Hye;Shin, Tae-Joon;Lee, Byung-Hwan;Hwang, Sung-Hee;Kang, Ji-Yeon;Kim, Hyun-Joong;Park, Chan-Woo;Nah, Seung-Yeol
    • Journal of Ginseng Research
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    • v.35 no.4
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    • pp.471-478
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    • 2011
  • Ginseng, the root of Panax ginseng, is one of the oldest herbal medicines. It has a variety of physiological and pharmacological effects. Recently, we isolated a subset of glycolipoproteins that we designated gintonin, and demonstrated that it induced transient change in intracellular calcium concentration $([Ca^{2+}]_i)$ in cells via G-protein-coupled receptor signaling pathway(s). The previous method for gintonin isolation included multiple steps using methanol, butanol, and other organic solvents. In the present study, we developed a much simple method for the preparation of gintonin from ginseng root using 80% ethanol extraction. The extracted fraction was designated edible gintonin. This method produced a high yield of gintonin (0.20%). The chemical characteristics of gintonin such as molecular weight and the composition of the extract product were almost identical as the gintonin prepared using the previous extraction regimen involving various organic solvents. We also examined the physiological effects of edible gintonin on endogenous $Ca^{2+}$-activated $Cl^-$ channel activity of Xenopus oocytes. The 50% effective dose was $1.03{\pm}0.3\;{\mu}g$/mL. Finally, since gintonin preparation through ethanol extraction is easily reproducible, gintonin could be commercially applied for ginseng-derived functional health food and/or drug following the confirmations of in vitro and in vivo physiological and pharmacological effects of gintonin.

Effects of Tracheal Suction and Method of Bronchodilator Inhalation on Vital Signs and Pulmonary functions in Patients with Open Heart Surgery(OHS) (심장수술 환아에게 기도흡인과 기관지 확장제의 투여 방법이 활력징후 및 폐기능에 미치는 효과)

  • Song Hyo-Sook;Jun Tae-Gook;Park Pyo-Won;Kim Kyoung-Eun;Chung Ji-Hye
    • Journal of Korean Academy of Fundamentals of Nursing
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    • v.10 no.1
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    • pp.96-107
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    • 2003
  • Objective: The purpose of this study was to identify the effects of tracheal suction and the effects of different methods of bronchodilator inhalation (Ultrasonic nebulizer: MDI puff, MDI puff with spacer) in VSD surgery patients. Material & Method: From June 2001 to March 2002, sixty consecutive patients were randomly assigned to a control group (n= 15), ultrasonic nebulizer group (n=15), metered dose inhalation (MDI) puff group (n=15) and MDI with spacer group (n=15). Vital signs (HR, BP, CVP), ABGA and pulmonary functions were measured before suction (baseline for suction), after suction, 15 minutes after suction (base of bronchodilator inhalation), 30 minutes after bronchodilator inhalation, and 2 hours after bronchodilator inhalation. Stastistical analysis was performed using SPSS software. Repeated measure ANOVA was used to examine the effects of tracheal suction. One way ANOVA with Bonferroni's correction and multiple range test (the least significant difference test) were used to examine the effects of albuterol inhalation. Result: 1. Heart .ate increased significantly immediately after suction (p<.01) and recovered 15 minutes after suction. 2. $PaO_2$ and PH decreased significantly immediately after suction (p<.05) and $PaO_2$ recovered 15 minutes after suction. $PaCO_2$ increased immediately after suction and significantly 15 minutes after suction (p<.01). But changes in vital signs and ABGA were within the normal range. 3. Tidal volume decreased significantly 15 minutes after suction (p<.05). 4. Changes of HR and tidal volume were greater in the nebuizer group compared to the other groups (p<.05) 30 minutes after bronchodilator inhalation and recovered 2 hours after bronchodilator inhalation. 5. Changes of airway deadspace was greater in the nebulizer group compared to the control group and MDI puff group 30 minutes after albuterol inhalation (p<.05) and at 2 hours (p<.01). Conclusion: Tracheal suction did not have significant effect on vital signs and pulmonary functions after OHS. Although the methods of bronchodilator inhalation did not showed any significant difference on pulmonary function, the nebulizer method increased $PaO_2$ (20%) and tidal volume transiently. If the patient needs bronchodilator inhalation with bronchospasm after OHS, the nebulizer method is the best choice. More study on the effects of bronchodilator inhalation in bronchospasm group is needed.

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Effects of Substance P on the Release of Cytokines from Immune Cell Lines (면역세포의 cytokine 유리에 미치는 substance P의 영향)

  • Lee, Jin-Yong;Kim, Soo-Ah;Seo, Seok-Ran;Kim, Hyong-Seop
    • Journal of Periodontal and Implant Science
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    • v.27 no.2
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    • pp.425-441
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    • 1997
  • The neuropeptide substance P(SP) has been implicated in the mediation of inflammation and immune-mediated disease such as arthritis. Recently, it was reported that SP was markedly increased around the blood vessels in inflamed gingiva as well as in close association with the inflammatory cell infiltrate. These results support that SP may contribute to the pathophysiology of neuronal inflammation in human periodontal tissues. SP may regulate inflammatory/immune responses by stimulating the proliferation of human T cells, differentiation and antibody-secreting potential of B cells, macrophage respiratory burst, connective tissue proliferation, and the secretion of cytokines from monocytes and T cells. Here, I studied potential role of SP as a costimulatory chemical signal in inflammatory/immune responses, by determining the released proinflammatory cytokines such as $MIP-1{\alpha}$, $IL-1{\beta}$, and IL-6 from culture supernatants of homogeneous immune cell lines. Serum free cell supernatants were concentrated with TCA precipitation, fractionated with SDS-PAGE, and subjected into western blot analysis. Among 15 cell lines tested, macrophage/monocyte cell line RAW264.7 and WRl9m.1 showed the highest level of induction of $MIP-1{\alpha}$ when stimulated with LPS. Discrete IL-6 bands with multiple forms of molecular mass were detected from supernatants of B cell lines A20(32kDa), Daudi(32, 35kDa), and SKW6.4(29kDa), which were expressed constitutively. $IL-1{\beta}$ could not be detected by the method of western blot analysis from supernatants of all cell lines tested except RAW264.7, WRl9m.1, and erythroid cell line K562 which showed the least amount of $IL-{\beta}$ secretion. SP $10^{-9}M$ with suboptimal dose of LPS treatment showed synergistic induction of $MIP-1{\alpha}$ release from RAW264.7 or WR19m.1, and also IL-6 release from A20, but this synergism is not the case in costimulation of RAW264.7 or WRl9m.1 with SP $10^{-9}M$ and TPA. Although treatment of T cell line CTLL-R8 with SP $10^{-7}M$ or PHA+TPA induced modest level of $MIP-1{\alpha}$ secretion, synergism was not observed when they are applied together. These findings all together suggest the possibility of a regulatory role of SP in inflammatory/immune reaction through differential modulation of bioactivities of other chemical cosignals.

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Interleukin-$1{\beta}$ induces bone resorption by regulation of prostaglandin $E_2$ synthesis and plasminogen activator activity, and TGF-$\beta$ inhibits bone resorption of rat bone cells (쥐의 골세포에서 $PGE_2$ 합성과 plasminogen activator 활성 조절에 의한 IL-$1{\beta}$의 골 흡수유도와 TGF-$\beta$에 의한 골 흡수 억제 기전에 관한 연구)

  • Kim, Young-Hun;Lee, Young-Jun;Chung, Kyu-Rhim;Park, Young-Guk
    • The korean journal of orthodontics
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    • v.30 no.6 s.83
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    • pp.713-721
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    • 2000
  • Bone cells produce multiple growth factors and cytokines that have effects on bone metabolism and can be incorporated into the bone matrix. The present study was designed to extend these observations by examining the interactions between transforming growth factor-$\beta$(TGF-$\beta$) or interleukin-$1\beta$(rhIL-$1\beta$) and bone cells in a rat long bone culture model. IL-$1\beta$ regulates several activities of the osteoblast cells derived from rat long bone explants in vitro. IL-$1\beta$ stimulated cellular proliferation as well as the synthesis of prostaglandin $E_2$ and Plasminogen activator activity in the cultured cells in a dose-dependent manner. TGF-$\beta$ is present in the bone matrix and potentially released during bone resorption. TGF-$\beta$ reduced basal bone resorption and inhibited vitamin $D_3[1,25(OH)_2D_3]$-induced bone resorption in rat long bone cells. These results support the role of IL-$1\beta$ in the pathological modulation of bone cell metabolism, with regard to implication in the Pathogenesis of osteoporosis by IL-$1\beta$, and that TGF-$\beta$ positively inhibits the bone resorption.

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Inhibition of advanced glycation end product formation by burdock root extract (우엉 뿌리 추출물의 최종당화산물 형성 억제 효능)

  • Lee, Darye;Kim, Choon Young
    • Journal of Nutrition and Health
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    • v.49 no.4
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    • pp.233-240
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    • 2016
  • Purpose: Diabetic complications are a major concern to manage progression of diabetes. Production of advanced glycation end products (AGEs) due to high blood glucose is one of the mechanisms leading to diabetic complications. Multiple pharmacologic AGE inhibitory agents are currently under development, but clinical applications are still limited due to safety issues. Thus, it is necessary to identify a safe anti-glycation agent. It is known that burdock roots have antioxidant, anti-inflammatory, and anti-cancer activities. The objective of the present study was to investigate the inhibitory role of burdock roots on the formation of high glucose-induced glycation of bovine serum albumin (BSA). Methods: In this study, glycation of BSA by glucose, galactose, or fructose at $37^{\circ}C$ for 3 weeks was assessed based on levels of ${\alpha}$-dicarbonyl compounds (early-stage glycation products), fructosamine (intermediate products of glycation), and fluorescent AGEs (late-stage glycation products). In order to compare the inhibitory actions of burdock root extract in AGE formation, aminoguanidine (AG), a pharmacological AGE inhibitor, was used as a positive control. Results: BSA glycation by glucose, fructose, and galatose was dose- and time-dependently produced. Burdock root extract at a concentration of 4 mg/mL almost completely inhibited glucose-induced BSA glycation. The results demonstrate that burdock root extract inhibited AGE formation with an $IC_{50}$ value of 1.534 mg/mL, and inhibitory activity was found to be more effective than the standard anti-glycation agent aminoguanidine. This study identified a novel function of burdock root as a potential anti-glycation agent. Conclusion: Our findings suggest that burdock root could be beneficial for preventing diabetic complications.

Anti-Varicella Zoster Virus Activity of Water Soluble Components of Elfvingia applanata Alone and in Combinations with Interferons (잔나비걸상 수용성성분의 항-Varicella Zoster Virus 작용과 Interferon과의 병용효과)

  • Kim, Young-So;Lee, Seong-Kug;Lee, Young-Nam;Han, Seong-Sun
    • The Korean Journal of Mycology
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    • v.27 no.3 s.90
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    • pp.237-241
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    • 1999
  • To search for less toxic antiviral agents from Basidiomycetes, the water soluble components (=EA), were isolated from the carpophores of Elfvingia applanata (Pers.) Karst. Anti-varicella zoster virus (Oka strain; anti-VZV/Oka) activity of EA was examined in MRC-5 cells by plaque reduction assay in vitro. And the combined antiviral effects of EA with interferon (IFN) alpha or IFN gamma were examined on the multiplication of VZV/Oka. EA exhibited a dose-dependent reduction in the plaque formation of VZV/Oka with 50% effective concentration $(EC_{50})$ of $464.14\;{\mu}g/ml$. The results of the combination assay were evaluated by the combination index (CI) that was calculated by the multiple drug effect analysis. The combination of EA with IFN alpha showed partially synergistic or additive effects with CI values of $0.83{\sim}1.09$ for 50%, 70%, 90% effective levels, and those with IFN gamma showed antagonism with CI values of $1.20{\sim}1.24$.

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