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Development and Validation of the Determination of Sorafenib in Human Plasma using Tandem Mass Spectrometry Coupled with Liquid Chromatography (고속액체크로마토그래피 텐덤질량분석기법을 이용한 사람 혈장 내 소라페닙 농도분석법의 개발 및 검정)

  • Park, Daejin;Lee, Sunggon;Kim, Woomi
    • Journal of Life Science
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    • v.22 no.11
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    • pp.1456-1462
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    • 2012
  • Sorafenib is a multikinase inhibitor and an oral anticancer drug approved for the treatment of patients with advanced renal cell carcinoma and those with unresectable hepatocellular carcinoma. The purpose of this study was to develop an efficient method of the determination of sorafenib in human plasma using tandem mass spectrometry coupled with liquid chromatography (LC/MS/MS) and validate the method by the guidelines of the Korean Food and Drug Administration (KFDA). Plasma samples ($100{\mu}l$) were added with chlorantraniliprole as an internal standard and then mixed with the 0.1% formic acid-containing extraction solution composed of isopropyl alcohol and ethyl acetate (1:4, v/v). After centrifugation, the supernatant was concentrated at $45^{\circ}C$ under negative pressure and centrifugal force. The residue was reconstituted with a mobile phase and injected into the HPLC instrument using a reverse phase Waters XTerra$^{TM}$ C18 column (particle size $3.5{\mu}m$). Liquid chromatography was carried out within the run time of 5 min using a mobile phase composed of buffer (0.1% formic acid and 10 mM ammonium formate), methanol, and acetonitrile (1:6:3, v/v/v). The analytes were monitored by tandem mass spectrometry in the multiple reaction monitoring method programmed to detect sorafenib at 'm/z 465.2 ${\rightarrow}$ 252.5' and chlorantraniliprole at 'm/z 484.4 ${\rightarrow}$ 286.2' with positive electrospray ionization mode ($ES^+$). The result showed the proper linearity ($r^2$ > 0.99) over the range of 2,000-5,000 ng/ml with good accuracy (90.7-103.9%) and precision (less than 10%). The newly developed method using LC/MS/MS was validated by the guideline of KFDA and identified as more sensitive compared to the previous methods.

Comparison of Pakistani Ephedra Herba and Chinese Ephedra Herba Containing Gangjihwan in the Improvement Effects of Weight Loss in a High Fat Diet-Fed Obese Mice (고지방식이 비만마우스 모델에서 파키스탄산 및 중국산 마황으로 조성된 강지환(降脂丸)의 체중감량 효과 비교)

  • Kim, Byeong Chul;Seok, Hoa Jun;Yoo, Jae Sang;Ku, Ja Ryong;Yoon, Ki Hyeon;Jo, Ju Heum;Jang, Du Hyon;Jung, Yang Sam;Kim, Jong Hoon;Ahn, Ye Ji;Woo, Sangee;Yoon, Miso;Shin, Soon Shik
    • Herbal Formula Science
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    • v.22 no.2
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    • pp.63-76
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    • 2014
  • Objectives : This study investigated the improvement effects of Pakistani (DF-a) and Chinese Ephedra herba-containing Gangjihwan (DF-b) on obesity in a high fat diet-fed obese mouse model. Methods : Eight-week-old C57BL/6N mice were divided into four groups: a normal lean group given a standard diet, an obese control group given a high fat diet, and DF-a and DF-b groups given a high fat diet with DF-a (80 mg/kg), and DF-b (80 mg/kg), respectively. After 8 weeks of treatment, body weight gain, feeding efficiency ratio, blood lipid markers, fat weight and histology were examined. Results : 1. Body weight gain and fat mass were significantly decreased in DF-a and DF-b groups compared with control. The extent of decreases was eminent in DF-a group. 2. Feeding efficiency ratio and circulating leptin concentration were significantly decreased in DF-a and DF-b groups compared with control, whereas circulating adiponectin concentration was increased in DF-a and DF-b groups compared with control. 3. Consistent with their effects on body weight gain and fat mass, circulating concentrations of triglyceride, glucose and insulin were decreased in DF-a and DF-b groups compared with control. 4. The size of adipocytes were decreased by DF-a and DF-b compared with control, whereas the adipocyte number per unit area was increased by them, suggesting that DF-a and DF-b decreased the number of large adipocytes. 5. Consistent with their effects on body weight gain, liver fibrosis was reduced in DF-a and DF-b groups compared with control. Conclusions : In conclusion, these results suggest that DF-a and DF-b not only decrease feeding efficiency ratio, plasma leptin concentration, and blood anti-obesity biomarkers, but also reduce fat mass, contributing to the improvement of obesity. DF-a and DF-b also inhibit liver fibrosis. In addition, these effects were similar between Pakistani Ephedra herba and Chinese Ephedra herba-containing Gangjihwan.

Comparison of Gangjihwan and Combination of Gangjihwan and Gamisochehwan in the Improvement Effects of Weight Loss in a High Fat Diet-Fed Obese Mice (고지방식이 비만마우스 모델에서 파키스탄산 마황으로 조성된 강지환(降脂丸)의 단독 투여와 강지환합가미소체환(降脂丸合加味消滯丸)의 병용 투여의 체중감량 효과 비교)

  • Seok, Hoa Jun;Yoo, Jae Sang;Ku, Ja Ryong;Yoon, Ki Hyeon;Jo, Ju Heum;Jang, Du Hyon;Jung, Yang Sam;Kim, Jong Hoon;Kim, Byeong Chul;Roh, Jong Seong;Lee, Hye Rim;Lee, Hyunghee;Yoon, Michung;Shin, Soon Shik
    • Herbal Formula Science
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    • v.22 no.2
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    • pp.105-120
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    • 2014
  • Objectives : This study was investigated the improvement effects of Gangjihwan (DF) and combination of Gangjihwan and Gamisochehwan (GSH) on obesity in a high fat diet-fed obese mouse model. Methods : Eight-week-old C57BL/6N mice were divided into four groups: a normal lean group given a standard diet, an obese control group given a high fat diet, and DF and DF+GSH groups given a high fat diet with DF (40 mg/kg), and DF+GSH (80 mg/kg), respectively. After 8 weeks of treatment, body weight gain, feeding efficiency ratio, blood lipid markers, fat weight and histology were examined. Results : 1. Body weight gain and fat mass were significantly decreased in DF and DF+GSH groups compared with control. The extent of decreases was eminent in DF+GSH group. 2. Feeding efficiency ratio and circulating concentration of leptin were decreased in DF and DF+GSH groups compared with control. These decreases were significant in DF+GSH group. 3. Consistent with their effects on body weight gain and fat mass, circulating concentrations of triglyceride, glucose and insulin were decreased in DF and DF+GSH groups compared with control. 4. The size of adipocytes was decreased by DF and DF+GSH compared with control, whereas the adipocyte number per unit area was increased by them, suggesting that DF and DF+GSH decreased the number of large adipocytes. 5. Consistent with their effects on body weight gain, liver fibrosis was also improved in DF and DF+GSH groups compared with control. Conclusions : In conclusion, these results suggest that DF and DF+GSH groups decrease feeding efficiency ratio, plasma leptin concentration, blood anti-obesity biomarkers and fat mass, improves body weight gain contributing to the inhibition of liver fibrosis. In addition, these effects were more effective in DF+GSH combination group than in DF-only group.

An Estimation of Land use by Land Values in the Great Cities - focusing on five great cities - (지가에 의한 대도시의 토지이용예측 - 5개 대도시를 중심으로 -)

  • Lee, Hyun-Wook
    • Journal of the Korean association of regional geographers
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    • v.7 no.1
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    • pp.83-95
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    • 2001
  • The purpose of this study is to examine that we can estimate land use by land values in 5 great cities. For this purpose, I calculated the percentage that each lot value makes up of the highest land values in the city as a indicator. I think this rate is very useful in the comparative study about many cities. At first, I set up four hypotheses based on my preceding studies. Hypothesis 1, the range of CBD can be estimated as having about 10% of the peak land values. Hypothesis 2, when the peak rate of concentric circle of land values seperated from CBD circle is about 30% of the peak land values, that is sub-CBD. Hypothesis 3, generally, a lot of having about 5% of the peak land values represents residential land commercial land use. Hypothesis 4, a lot of having about 3% of the peak land values represents only residential land use. The data on land values in five great cities were got from public notification on land values(1999) of the Ministry of Construction & Transportation. I selected highest lot values from many standard lot value in each Tong(the minimum administrative unit) in each cities. And I drew land values isopleth. Through that isopleth, I identified CBD cmd sub-CBD. Through the book of public notification on land values, I identified what land use are lots of having over 10%, about 5%, below 3% of the peak land values. As a result, we identified land use can be estimated by the percentage that each lot value makes up of the highest land values in the city. The bigger urban size becomes and the more stable land use becomes, the higher fitness of hypotheses becomes. The lowest degree of fitness about 4 hypotheses among 5 great cities showed in Inchon. Because Inchon lies adjacent to the greatest Seoul. The percentage that showed the lowest degree of fitness is 5% of the highest land values. The land use on lots of having about 5% of the peak land values is different from each other according to regional character in city.

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A Comparison Study of Aerosol Samplers for PM10 Mass Concentration Measurement (PM10 질량농도 측정을 위한 시료채취기의 비교 연구)

  • Park, Ju-Myon;Koo, Ja-Kon;Jeong, Tae-Young;Kwon, Dong-Myung;Yoo, Jong-Ik;Seo, Yong-Chil
    • Journal of Korean Society of Environmental Engineers
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    • v.31 no.2
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    • pp.153-160
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    • 2009
  • A PM10 (aerodynamic diameter${\leq}$10 ${\mu}m$) sampler is used to quantify the potential human exposure to suspended particulate matter (PM) and to comply with the governmental regulation. This study was conducted to compare and evaluate the same PM10 cutpoint and different slopes between United States Environmental Protection Agency (USEPA) PM10 sampling criterion and American Conference of Governmental Industrial Hygienists/$Comit\acute{e}$ $Europ\acute{e}en$ de Normalization/International Organization for Standardization thoracic PM10 sampling criterion through theory and experiment. Four PM10 samplers according to the USEPA criterion and one RespiCon sampler in accordance with the thoracic PM10 criterion were used in the present study. In addition, one DustTrak monitor was used to measure real time PM10 mass concentrations. All six aerosol samplers were tested in a PM generation chamber using polydisperse fly ash. Theoretical mass concentrations were calculated by applying the measured particle size distribution characteristics (geometric mean = 6.6 ${\mu}m$, geometric standard deviation = 1.9) of fly ash to each sampling criterion. The measured mass concentrations through a chamber experiment were consistent with theoretical mass concentrations in that a RespiCon sampler with the thoracic PM10 criterion collected less PM than a PM10 sampler with the USEPA criterion. The overall chamber experiment results indicated, when a PM10 sampler was used as a reference sampler, that (1) a RespiCon sampler had a normalizing factor of 1.6, meaning that this sampler underestimated an average 60% of PM10 mass sampled from a PM10 sampler, and (2) a DustTrak real-time monitor using a PM10 inlet had a calibration factor of 2.1.

Application of a New Conjugation Method to Fish Pathogenic Bacteria Containing R Plasmid for the Analysis of Drug-Resistant Status in Aquaculture (새로운 conjugation 방법을 응용한 R plasmid 함유 어병세균의 분리와 양식장 내성균의 현황 분석)

  • Yoo Min Ho;Jeong Joon Beom;Kim Eun Heui;Lee Hyoung Ho;Jeong Hun Do
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.35 no.2
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    • pp.115-121
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    • 2002
  • To develop a new method of conjugation and to determine the distribution of R plasimds, we isolated multi-drug resistant strains from fish pathogenic bacteria in the farms of south and east seacoasts of Korea. Out of the 134 isolates examined, 10 showed resistance to chloramphenicol, tetracycline, streptomycin, ampicillin, colistin, nalidixic acid, oxolinic acid and kanamycin. One out of 10 multi-drug resistance bacteria, Vibfio damsela JE1 (V. damsela JE1), contained transferable R plasmid of chlorarnphenicol- tetracycline resistance genes and other nucleic acids encoding ampicillin and kanamycin resistance. The presence of the R plasmid was confirmed by conjugation using the chromocult medium (CC) as a selective and differential medium for transconiugants with identification based on the growth or colors of the colonies. The frequency of R plasmid transfer with filter mating method was come out much higher than that of broth mating method and appeared to be dependent upon the mating time and temperature. The optimum conditions for filter mating method were found to be 30$^{\circ}C$ and 24hrs as mating temperature and period, respectively, Moreover, donor cells with R plasmid, both isolate and standard bacteria, were shown to have an ability to transfer the plasmid against Escherichia coli K-12 HB101 (E. coli HB101) and Edwardsiella tarda (E. tarda) RE14 at fairly high frequencies, finally, we isolated 3 isolates of Sphingomonas sp., carrying R plasmid from 12 multi-drug resistant bacteria in normal microflora of the flounder (Paralichthys olivaceus) group used for the isolation of V emsela JE1 four months before. The same size and gene transfer chayateristics of R plasimds with those of V damsela JE1 confirmed that normal microflora have the reservoir activity for R plasmid in natural aquatic environment.

The Flora of Vasular Plants and the Vegetation on the Tidal Flat in Jebudo(Island) (제부도 갯벌식생과 소산 식물상에 관한 연구)

  • Shin, Kyung-Mi;Ahn, Young-Hee
    • Korean Journal of Environment and Ecology
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    • v.20 no.1
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    • pp.52-69
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    • 2006
  • The flora of vascular plants and the vegetation on the tidal flat was investigated in Jebudo located at Hwaseong city of Gyeonggi-do province from 2004 to 2005. Jebudo has been considered to show difference from the flora which is peculiar to island as it became semi-land by free traffic to mainland with the installation of a road which had enabled entry into the Jebudo in 1991 due to sea-splitting phenomenon. The result of the vascular plants in Jebudo were consissted of 305 taxa; 264 species, 38 varieties and 3 forms of 202 genera of 74 families. As a result of examination by distinctive survey areas within Jebudo, a tidal flat(I) region where the halophyte was being spread has been researched as 7 taxa; 7 species of 6 genera of 5 families. The taxa in Godo-Island(II) was reseached as 50 taxa; 39 species, 11 varieties and 42 genera of 24 families. The taxa in Sand dune area(III) was reseached as 61 taxa; 52 species and 9 varieties of 53 genera of 25 families. The most plant species was reseached in Mt. Tapjae (IV) reaseach area among the reseach areaes 136 taxa; 118 species, 17 varieties and 1 form of 108 genera of 55 families. The taxa in Dangje Mt.(V) was reseached as 119 taxa; 105 species, 13 varieties and 1 form of 95 genera of 45 familes. The taxa in Dongmi Mt. (VI) was reseached as 100 taxa; 85 species and 15 varieties of 83 enera of 43 families. The taxa in Paddy field(VII) was reseached as 120 taxa; 106 species, 13 varieties and 1 form of 86 genera 31 families. Especially, a Crypsinus hastatus community which is a rare plant designated by Korea forest service and a preservation plant designated by the natural environment preservation law (1998) has been discovered at a cliff of Topjae mountain near the ferry located at the northeast side. According to the result of researching halophyte communities which make up the zonation according to the environmental gradient, the communities were being formed in the order of Limonium tetragonum community, Phragmites communis community, Carex scabrifolia community, Triglochin maritimum community and Carex scabrifolia community in accordance with the order of soil particle size with breakwater as their standard.

Release Strategy for the Red Fox (Vulpes vulpes) Restoration Project in Korea Based on Population Viability Analysis (개체군 생존력 분석을 이용한 여우복원사업 방사전략)

  • Lee, Hwa-Jin;Lee, Bae-Keun;Kwon, Gu-Hui;Chung, Chul-Un
    • Korean Journal of Environment and Ecology
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    • v.27 no.4
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    • pp.417-428
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    • 2013
  • The red fox (Vulpes vulpes), listed as a Class I endangered species by the Ministry of Environment of Korea, has been considered to be extinct in South Korea since the 1980s, and an intensive restoration project has been underway in Sobaeksan national park. This study was carried out to develop a suitable model for the red fox reintroduction program based on Population viability analysis (PVA) by using the VORTEX program. If 10 animals (5 females and 5 males) were continuously released into the initial zero population every year for 10 years, population growth rate and extinction probability over the next 50 years after the introduction of the population were $0.018{\pm}0.204$ and 0.354, respectively; the maximum population size was 116.34 at the 16th year after the first release, and a reduction rate of 1.22 every year from the 17th year was inferred. We found that additional releases would be needed from the 17th year after the initial release to maintain a positive growth rate and to prevent the extinction of the released red foxes, and releasing more than 12 individuals every year would be needed for the long-term, continuous existence of red foxes. By contrast, if fewer than 6 red fox individuals were released the extinction probability over the next 50 years was more than 80%. To maintain the minimum population growth rate, the release of more than 8 individuals were needed for positive population growth. The population growth rate was more stable when 10 animals in the change of their sex rate every year from the set value were released as the female-to- male sex ratio of 6:4 rather than 1:1. However, if the female-biased sex ratio was increased by more than 7:3, a negative population growth was expected. The occurrence rate of roadkill and poaching are important factors in the red fox restoration project. The extinction probability was decreased to 30% if each factor was decreased to 3% based on the standard baseline; however, if each factor was increased to more than 3%, an extinction rate of about 90% was reached over the next 50 years.

Experimental Study on the Infiltration Loss in Plastic Greenhouses Equipped with Thermal Curtains (보온커튼을 설치한 플라스틱 온실의 틈새환기전열량 실측조사)

  • Nam, Sang-Woon;Shin, Hyun-Ho
    • Journal of Bio-Environment Control
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    • v.24 no.2
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    • pp.100-105
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    • 2015
  • The calculation method of infiltration loss in greenhouse has different ideas in each design standard, so there is a big difference in each method according to the size of greenhouses, it is necessary to establish a more accurate method that can be applied to the domestic. In order to provide basic data for the formulation of the calculation method of greenhouse heating load, we measured the infiltration rates using the tracer gas method in plastic greenhouses equipped with various thermal curtains. And then the calculation methods of infiltration loss in greenhouses were reviewed. Infiltration rates of the multi-span and single-span greenhouses were measured in the range of $0.042{\sim}0.245h^{-1}$ and $0.056{\sim}0.336h^{-1}$ respectively, single-span greenhouses appeared to be slightly larger. Infiltration rate of the greenhouse has been shown to significantly decrease depending on the number of thermal curtain layers without separation of single-span and multi-span. As the temperature differences between indoor and outdoor increase, the infiltration rates tended to increase. In the range of low wind speed during the experiments, changes of infiltration rate according to the outdoor wind speed could not find a consistent trend. Infiltration rates for the greenhouse heating design need to present the values at the appropriate temperature difference between indoor and outdoor. The change in the infiltration rate according to the wind speed does not need to be considered because the maximum heating load is calculated at a low wind speed range. However the correction factors to increase slightly the maximum heating load including the overall heat transfer coefficient should be applied at the strong wind regions. After reviewing the calculation method of infiltration loss, a method of using the infiltration heat transfer coefficient and the greenhouse covering area was found to have a problem, a method of using the infiltration rate and the greenhouse volume was determined to be reasonable.

Verification of Indicator Rotation Correction Function of a Treatment Planning Program for Stereotactic Radiosurgery (방사선수술치료계획 프로그램의 지시자 회전 오차 교정 기능 점검)

  • Chung, Hyun-Tai;Lee, Re-Na
    • Journal of Radiation Protection and Research
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    • v.33 no.2
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    • pp.47-51
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    • 2008
  • Objective: This study analyzed errors due to rotation or tilt of the magnetic resonance (MR) imaging indicator during image acquisition for a stereotactic radiosurgery. The error correction procedure of a commercially available stereotactic neurosurgery treatment planning program has been verified. Materials and Methods: Software virtual phantoms were built with stereotactic images generated by a commercial programming language, Interactive Data Language (version 5.5). The thickness of an image slice was 0.5 mm, pixel size was $0.5{\times}0.5mm$, field of view was 256 mm, and image resolution was $512{\times}512$. The images were generated under the DICOM 3.0 standard in order to be used with Leksell GammaPlan$^{(R)}$. For the verification of the rotation error correction function of Leksell GammaPlan$^{(R)}$, 45 measurement points were arranged in five axial planes. On each axial plane, there were nine measurement points along a square of length 100 mm. The center of the square was located on the z-axis and a measurement point was on the z-axis, too. Five axial planes were placed at z=-50.0, -30.0, 0.0, 30.0, 50.0 mm, respectively. The virtual phantom was rotated by $3^{\circ}$ around one of x, y, and z-axis. It was also rotated by $3^{\circ}$ around two axes of x, y, and z-axis, and rotated by $3^{\circ}$ along all three axes. The errors in the position of rotated measurement points were measured with Leksell GammaPlan$^{(R)}$ and the correction function was verified. Results: The image registration errors of the virtual phantom images was $0.1{\pm}0.1mm$ and it was within the requirement of stereotactic images. The maximum theoretical errors in position of measurement points were 2.6 mm for a rotation around one axis, 3.7 mm for a rotation around two axes, and 4.5 mm for a rotation around three axes. The measured errors in position was $0.1{\pm}0.1mm$ for a rotation around single axis, $0.2{\pm}0.2mm$ for double and triple axes. These small errors verified that the rotation error correction function of Leksell GammaPlan$^{(R)}$ is working fine. Conclusion: A virtual phantom was built to verify software functions of stereotactic neurosurgery treatment planning program. The error correction function of a commercial treatment planning program worked within nominal error range. The virtual phantom of this study can be applied in many other fields to verify various functions of treatment planning programs.