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Bioequivalence Test of Gabapentin 800 mg Tablets (가바펜틴 800밀리그람 정제의 생물학적동등성시험)

  • Kim, Se-Mi;Shin, Sae-Byeok;Kang, Hyun-Ah;Cho, Hea-Young;Lee, Yong-Bok
    • YAKHAK HOEJI
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    • v.52 no.4
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    • pp.299-305
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    • 2008
  • Gabapentin, 1-(aminomethyl) cyclohexaneacetic acid, is a amino acid derivative, and is clinically effective in the treatment of neuropathic pain and partial seizures of epilepsy as a complementary therapy. The purpose of the present study was to evaluate the bioequivalence of two gabapentin tablets, $Neurontin^{R}$ tablet 800 mg (Pfizer Pharmaceuticals Co., Ltd.) and Gabapenin tablet 800 mg (Hanmi Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of gabapentin from the two gabapentin formulations in vitro was tested using KP VIII Apparatus II method with 0.06 M HCI dissolution media. Twenty six healthy male subjects, $23.85{\pm}2.24$ years in age and $69.40{\pm}11.11$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ crossover study was employed. After a single tablet containing 800 mg as gabapentin was orally administered, blood samples were taken at predetermined time intervals and the concentrations of gabapentin in serum were determined using HPLC with fluorescence detector. The dissolution profiles of two formulations were similar in the tested dissolution media. The pharmacokinetic parameters such as $AUC_{t}$, $C_{max}$ and $T_{max}$ were calculated, and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_{t}$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Neurontin^{R}$, were 1.28%, 0.63% and 0.62% for $AUC_{t}$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g., $log0.9097{\sim}log1.1598$ and $log0.8919{\sim}log1.1262$ for $AUC_{t}$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Gabapenin tablet 800 mg was bioequivalent to $Neurontin^{R}$ tablet 800 mg.

Isotope-Aided Micronutrient Studies in Rice Production with Special Reference to Zinc Deficiency (II) -Residual Effect of $^{65}Zn$ Labelled Fertilizers-

  • Kim, Tai-Soon;Kim, Jae-Sung;Kim, Jin-Se
    • Nuclear Engineering and Technology
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    • v.11 no.1
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    • pp.47-54
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    • 1979
  • A field experiment has been carried out to evaluate the residual effect of zinc fertilizers by rice plant grown under flooded conditions in the field. The results obtained are summarized as fellows ; Residual effect of zinc fertilizers on yields of rough and hulled grains showed slight increases. Effect of zinc application methods on yields of the grains were shown that zinc mixed treatment could be more effectively utilized than treatment of zinc on the soil surface. In case of levels of zinc application, 5 kg zinc per hectare represented high yields of the grains than those obtained from 10kg and 20kg zinc placement per hectare respectively. Regarding the form of zinc fertilizers, the urea-zinc complex showed less effective on yields of the grains than did the zinc sulfate. This phenomenon was consistent with the previous result. Yields of total zinc in rice plant grown on the rice straw added soils (Treatment No. 2 and 8) and the urea-zinc complex treated soil were increased markedly as compared to those data obtained from the previous year. The percentage of zinc derived from fertilizer decreased largely as compared to that of the first year crop. The yield of fertilizer zinc in rice plant decreased slightly in the most zinc treatments but in the case of treatments of zinc mixed with the straw added soil and the urea-zinc complex increased reversely as compared to the previous results. The mixed application of zinc with soil showed higher yield of fertilizer zinc than the soil surface placement. Approximately from 4.6 to 24.3 per cent of zinc taken up by rice plants were derived from the fertilizer zinc. Zinc fertilizer use efficiency ranged from 0.213 to 0.584 per cent when 5 kg zinc per hectare applied.

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Correlation between TOC and Water Pollution Index in Major Streams of Gwangju (광주지역 주요하천에서 TOC 특성과 수질오염지표와의 상관성에 관한 연구)

  • Yang, Yoon-Cheol;Lee, Dae-Haeng;Lee, Kyung-Seog;An, Sang-Su;Song, Hyeong-Myeong;Lee, Se-Haeng;Yoon, Sang-Hoon;Kim, Sun-Jung;Jeon, Hong-Dae;Cho, Young-Gwan;Seo, Gwang-Yeob
    • Journal of Korean Society on Water Environment
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    • v.33 no.2
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    • pp.203-210
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    • 2017
  • This study was performed to verify the replacement of COD to TOC, which is more accurate and reliable in analysis, as the water quality pollution index and to investigate the characteristics of water quality and the correlations for organic matter, suspended solids and nutrient materials during 2012 to 2015. The oxidation rates were compared by calculating the values of BOD-C/TOC & COD-C/TOC. The average value of TOC was 3.4(1.1 ~ 8.0) mg/L at 14 sites during the period. The ratios of BOD-C/TOC and COD-C/TOC, that mean the resolvability amounts among all carbon materials, were 28.8% and 62.7%, respectively. The correlation coefficient of TOC to COD at all sites was 0.718 (p<0.01), the highest value in comparing all items. The correlation coefficient of TOC to COD at Gwangju stream was 0.753 (p<0.01), the highest compare to the values at other rivers. The correlation coefficient of TOC to COD was 0.757 (p<0.01) at all sites in the range of TP-III ($0.1{\leq}TP$) and the value was 0.762 (p<0.01) in the range of TN-II ($2.0{\leq}TN$<3.0). As a result, TOC could be used as a water pollution index of organic matter instead of COD.

Three Dimensional Comparative Study On The Accuracy Of Impression Technique Using New Impression Coping (새로운 인상용 코핑을 이용한 임플란트 인상법의 정확성에 대한 3차원적 비교 연구)

  • Kim, Se-Ra;Kim, In-Soo;Park, Sung-Jae;Lee, Byung-Ok;Ko, Sok-Min
    • Journal of Dental Rehabilitation and Applied Science
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    • v.26 no.3
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    • pp.323-337
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    • 2010
  • The objective of this study was to examine the availability of the new impression coping by comparing with conventional coping in implant pick-up impression technique. Five implant fixtures were installed on #14, 21, 23, 25, 27 in acrylic resin model. That model with 5 fixtures was standard model, which was divided 3 groups; using new flag type impression coping, conventional impression coping splinted with self-curing resin, conventional impression coping without splinting. We made metal circular cones for calculation 3-dimensional coordinates by attaching to implant fixtures or analogs. Three-dimensional relationships of each model were calculated. Data was analyzed by multiple ANOVA and Bonferroni. The accuracy of impression between using new flag type impression coping and conventional impression coping did not show differences in 3 - dimensional analysis.Within limitations of this study, the new flag type impression coping is available in implant pick-up impression technique.

Three Cases of Mitochondrial Disorders in the Neonatal Period (신생아기에 진단된 미토콘드리아 질환 3례)

  • Kim, Yoon-Hee;Lee, Young-Mock;Namgung, Ran;Kim, Jeong-Eun;Lee, Soon-Min;Park, Kook-In;Kim, Se-Hoon;Lee, Jin-Sung
    • Neonatal Medicine
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    • v.17 no.2
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    • pp.254-261
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    • 2010
  • Little is known about neonatal mitochondrial disease, though mitochondrial metabolic disorders may often present in the neonatal period because of the high energy requirement of neonate. In newborn period, common presentations are not specific and the disease course may be rapid and fatal. In this study, we report three cases of neonatal mitochondrial disease. The first case was strongly suspected because of sudden seizure and mental change with severe lactic acidosis, and multiorgan failure. Plasma lactate/pyruvate (L/P) ratio was increased to 55.6 with marked lactic aciduria and increased plasma alanin up to 2,237 nmol/mL. In the second patient, a peritoneal dialysis was performed for acute adrenal and renal failure, but metabolic acidosis persisted. Plasma L/P ratio was increased to 23.9, and MRC I (mitochondrial respiratory chain defect) was diagnosed through the enzymatic analysis of the muscles. The third case showed repetitive episode of lactic acidosis during the first two months of life, hypotonia, failure to thrive and feeding difficulties. We found markedly increased cerebrospinal fluid L/P ratio up to 57 though plasma L/P ratio(19.4) was borderline with increased plasma lactate. The lactate peak was prominent in brain magnetic resonance spectroscopy (MRS). MRC II was confirmed through muscle biopsy. Plasma lactate level and lactate peak of brain MRS were normalized after conservative treatment.

Conservative Surgery and Definitive Radiotherapy in Early Breast Cancer (보존적 유방 절제술과 근치적 방사선치료가 초기 유방암의 치료 성적에 미치는 효과)

  • Shin, Sei-One;Hong, Jung-Sook;Kim, Myung-Se;Lee, Young-Do;Kim, Sung-Kyu;Lee, Soo-Jung
    • Journal of Yeungnam Medical Science
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    • v.10 no.2
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    • pp.380-387
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    • 1993
  • Local excision and axillary dissection followed by radiation therapy to the breast has been shown to achieve equivalent local control and survival as mastectomy in an prospective randomized trials. We analyzed 28 cases of early breast cancer in order to evaluate the therapeutic effects of conservative surgery and definitive radiotherapy in the management of early breast cancer as possible alternative of simple mastectomy, retrospectively. Obtained results were as follows : 1. Treatment related acute side reactions are more prominant in the case of chemoradiotherapy group than radiotherapy alone group. 2. There were no cases of primary, regional or systemic failures on the last follow up examination. 3. Cosmetic results after treatment were satisfactory in 26 cases out of 28 cases on the last follow up examination. 4. There were no demonstrable differences of tumor control and cosmetic results between the treatment groups. Although, these results suggested that definitive radiotherapy after local excision would be a possible and desirable alternative instead of total mastectomy in the management of early breast cancers, analyzed cases were too small and follow up period was too short to evaluate the therapeutic effect of primary radiotherapy after local excision, exactly.

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Solvation in Mixed Solvent (III). Solvatochromic Analysis for the Solvent Effect of Binary Mixed Solvent (혼합용매에서의 용매화 (제3보). 이성분 혼합용매 중에서 용매효과에 대한 분광용매화 분석)

  • Lee, Ik-Choon;La, Sang-Mu;Lee, Bon-Su;Sohn, Se-Chul
    • Journal of the Korean Chemical Society
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    • v.28 no.4
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    • pp.210-216
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    • 1984
  • Solvatochromic comparison methods were applied to determine Taft's solvent parameters, ${\pi}^{\ast}$(solvent polarity-polarizability), ${\alpha}$(solvent hydrogen bond donor acidity) and ${\beta}$ (solvent hydrogen bond acceptor basicity) for MeOH-MeCN solvent mixtures. Swain's solvent parameters A(anion solvation scale) and B(cation solvation scale) were also determined by least square fitting of kinetic data in the same binary solvent mixtures. It was found that: (i)${\beta}$ depends on the basicity of the solvent and increases with the MeOH content owing to the increase in polymeric structure of methanol; (ii) ${\pi}^{\ast}$depends on the dipole moment of the solvent and increases with the MeCN content of the solvent; (iii) ${\alpha}$ increases rapidly with the MeOH content as the hydrogen bond donor acidity of the solvent mixtures increases. Taft's reaction constants a and s and Swain's reaction constants a and b were determined for the reactions reported from our laboratory previously using solvent parameters determined in this work. No meaningful inter-relationship was found between the two set of reaction parameters, but a good linear correlation was found between the ratios a/s and a/b. Solvent effect on the reaction mechanism, substituent effect and leaving group ability were examined in the light of these reaction constants ratios.

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In Vitro Neural Cell Differentiation Derived from Human Embryonic Stem Cells: Effects of PDGF-bb and BDNF on the Generation of Functional Neurons (인간 배아 줄기세포 유래 신경세포로의 분화: BDNF와 PDGF-bb가 기능성 신경세포 생성에 미치는 영향)

  • Cho, Hyun-Jung;Kim, Eun-Young;Lee, Young-Jae;Choi, Kyoung-Hee;Ahn, So-Yeon;Park, Se-Pill;Lim, Jin-Ho
    • Clinical and Experimental Reproductive Medicine
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    • v.29 no.2
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    • pp.117-127
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    • 2002
  • Objective: This study was to investigate the generation of the functional neuron derived from human embryonic stem (hES, MB03) cells on in vitro neural cell differentiation system. Methods: For neural progenitor cell formation derived from hES cells, we produced embryoid bodies (EB: for 5 days, without mitogen) from hES cells and then neurospheres (for $7{\sim}10$ days, 20 ng/ml of bFGF added N2 medium) from EB. And then finally for the differentiation into mature neuron, neural progenitor cells were cultured in i) N2 medium only (without bFGF), ii) N2 supplemented with 20 ng/ml platelet derived growth factor-bb (PDGF-bb) or iii) N2 supplemented with 5 ng/ml brain derived neurotrophic factor (BDNF) for 2 weeks. Identification of neural cell differentiation was carried out by immunocytochemistry using $\beta_{III}$-tubulin (1:250), MAP-2 (1:100) and GFAP (1:500). Also, generation of functional neuron was identified using anti-glutamate (Sigma, 1:1000), anti-GABA (Sigma, 1:1000), anti-serotonin (Sigma, 1:1000) and anti-tyrosine hydroxylase (Sigma, 1:1000). Results: In vitro neural cell differentiation, neurotrophic factors (PDGF and BDNF) treated cell groups were high expressed MAP-2 and GFAP than non-treated cell group. The highest expression pattern of MAP-2 and $\beta_{III}$-tubulin was indicated in BDNF treated group. Also, in the presence of PDGF-bb or BDNF, most of the neural cells derived from hES cells were differentiated into glutamate and GABA neuron in vitro. Furthermore, we confirmed that there were a few serotonin and tyrosine hydroxylase positive neuron in the same culture environment. Conclusion: This results suggested that the generation of functional neuron derived from hES cells was increased by addition of neurotrophic factors such as PDGF-bb or BDNF in b-FGF induced neural cell differentiation system and especially glutamate and GABA neurons were mainly produced in the system.

Synthesis of Protoberberine Derivatives and Their Biological Activities (Protoberberine의 고급지방산 유도체합성 및 활성연구(V))

  • Kim, Sin-Kyu;Kwon, Chang-Ho;Yook, Chang-Soo;Rho, Young-Soo;Seo, Seong-Hoon;Choung, Se-Young;Chung, Sung-Hyun;Kim, Dong-Hyun;Hwang, Soon-Ho
    • YAKHAK HOEJI
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    • v.36 no.1
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    • pp.1-6
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    • 1992
  • Irradiation of phenolbetaine in a stream of nitrogen produced 8,14-cycioberbine[1]. Compound[1] was treated with 10% HCl solution to give the 8-hydroxycycloberbine[2] in 67.7% yield. Subsequently addition of ethylchloroformate to the compound[2] gave rise to the 8-hydroxy-7-ethylcarboxy-9, 10-dimethoxy-2, 3-methylenelioxy-13-oxo-norochotensane[3] in 78% yield. Treatment of the compound[3] with bis-(2-chloroethyl)amine then lead to the 7-bis(2-chloroethyl)carbamyl-norochoteneare[4]. On the other hand the compound[5], which is the 8-methoxynorochotensane, was derived when compound[1] was treated with methanol in a few drops of BF. Treatment of the compound[6], and the compound[7], 7-bis(2-chloroethyl)-carbanyl-8-methoxy-norocheyensane, was then synthesized by reaction of the compound[6] with bis(2-chloroethyl) amine. In the other synthetic pathway when compound[5] was treated with $POCl_3$ in dried benzene, 13-chloro-6-ene-norochetensane[8] with 42% yield was formed. Finally the 13-bis-(2-chloroethyl) amino-8-methoxy-norochotensane[9] was produced when we treated the compound[8] with bis-(2-chloroethyl) amine. In another pathway, reaction between phenolbetaine which is the precursor of the compound[1] and benzoylchloride in dried chloroform gave us the 5,6,7 trihydro-2, 3-methylene-dioxy-9-chloromethyl-10, 11-dimethoxyphenylisoquinoline-8-benzoate[10] in 73% yield. The results of biological activities for these compounds are also presented in Table I and II.

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Anisotropy of Magnetic Susceptibility (AMS) of Granitic Rocks in the Eastern Region of the Yangsan Fault (양산단층 동편 화강암질암의 대자율 이방성(AMS))

  • Cho, Hyeong-Seong;Son, Moon;Kim, In-Soo
    • Economic and Environmental Geology
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    • v.40 no.2 s.183
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    • pp.171-189
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    • 2007
  • A study of anisotropy of magnetic susceptibility (AMS) was undertaken on Cretaceous granitic, volcanic and sedimentary rocks in the eastern region of the Yangsan fault, southeast Korea. A total of 542 independently oriented core samples collected form 77 sites were studied. The main magnetic mineral in granitic rocks is magnetite according to the magnitude of bulk susceptibility, high-temperature susceptibility variation and isothermal remanent magnetization. Both of magnetic lineation and foliation with NE-SW trends are revealed in the granitic rocks, while volcanic rocks show scattered directions and sedimentary rocks show only load foliation parallel to the bedding planes. The following evidences read to the conclusion that both magnetic fabrics in the granitic rocks have been obtained by a tectonic stress before full solidification of the magma: (i) A fully hardened granitic rocks would get hardly any fabric, (ii) Difference of the magnetic fabric trends with those of the geological structures in the granitic rocks themselves formed by brittle deformation after solidification (e.g. patterns of small-faults and joints), (iii) Kinking of biotite and undulose extinction in quartz observed under the polarizing microscope, (iv) Discordance of magnetic fabrics in the granitic rocks with those in the surrounding rocks. The NE-SW trend of the magnetic foliations suggests a NW-SE compressive stress of nearly contemporaneous with the emplacement of the granitic rocks. The compression should have caused a sinistral strike-slip movement of the Yangsan Fault considering the trend of the latter. As the age of the granitic rocks in the study area is reported to be around $60\sim70$ Ma, it is concluded that the Yangsan fault did the sinistral strike-slip movement during this time (L. Cretaceous Maastrichtian - Cenozoic Paleocene).