• Title/Summary/Keyword: P-Y curves

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Genetic Variations in the HIF1A Gene Modulate Response to Adjuvant Chemotherapy after Surgery in Patients with Colorectal Cancer

  • Zhang, Yi;Wang, Peng;Zhou, Xing-Chun;Bao, Guo-Qiang;Lyu, Zhuo-Ming;Liu, Xiao-Nan;Wan, Shao-Gui;He, Xian-Li;Huang, Qi-Chao
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.11
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    • pp.4637-4642
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    • 2014
  • Background: Hypoxia-inducible factor $1{\alpha}$ (HIF-$1{\alpha}$) plays an important role in regulating cell survival and angiogenesis, which are critical for tumor growth and metastasis. Genetic variations of HIF1A have been shown to influence the susceptibility to many kinds of human tumors. Increased expression of HIF-$1{\alpha}$ has also been demonstrated to be involved in tumor progression. However, the prognostic value of single nucleotide polymorphisms (SNPs) inthe HIF1A gene remains to be determined in most cancer types, including colorectal cancer (CRC). In this study, we sought to investigate the predictive role of HIF1A SNPs in prognosis of CRC patients and efficacy of chemotherapy. Materials and Methods: We genotyped two functional SNPs in HIF1A gene using the Sequenom iPLEX genotyping system and then assessed their associations with clinicopathological parameters and clinical outcomes of 697 CRC patients receiving radical surgery using Cox logistic regression model and Kaplan Meier curves. Results: Generally, no significant association was found between these 2 SNPs and clinical outcomes of CRC. In stratified analysis of subgroup without adjuvant chemotherapy, patients carrying CT/TT genotypes of rs2057482 exhibited a borderline significant association with better overall survival when compared with those carrying CC genotype [Hazard ratio (HR), 0.47; 95% confidence interval (95% CI): 0.29-0.76; P < 0.01]. Moreover, significant protective effects on CRC outcomes conferred by adjuvant chemotherapy were exclusively observed in patients carrying CC genotype of rs2057482 and in those carrying AC/CC genotype of rs2301113. Conclusions: Genetic variations in HIF1A gene may modulate the efficacy of adjuvant chemotherapy after surgery in CRC patients.

Age and growth of the Okhotsk atka mackerel, Pleurogrammus azonus in the coastal of Gangwon-do, East Sea (동해 강원도 연안 임연수어, Pleurogrammus azonus의 연령과 성장)

  • YANG, Jae-Hyeong;YOON, Byoung-Sun;KIM, Jong-Bin;CHOI, Young-Min;PARK, Jeong-Ho;LEE, Jae-Bong;PARK, Kie-Young;LEE, Dong-Jin
    • Journal of the Korean Society of Fisheries and Ocean Technology
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    • v.54 no.1
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    • pp.54-64
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    • 2018
  • The age and growth of Pleurogrammus azonus in the coastal of Gangwon-do, East Sea were determined, from monthly samples of commercial catches, caught by the gill net and set net fishery from January to December in 2008. Gonadosomatic index (GSI) began to increase in September, and reached the maximum between November and December. After spawning GSI began to decrease from January. The annuli of P. azonus are formed once a year, with the boundary between opaque and translucent zones forming from December to January. The relationships between fork length (FL) and body weight (BW) were $BW=0.005FL^{3.240}$($R^2=0.963$) for females and $BW=0.006FL^{3.238}$($R^2=0.946$) for males. The FLs at annuli formation in otoliths were back-calculated from the otolith-length relationship and were adjusted to von Bertalanffy growth curves to $FL_t=70.54(1-{\exp}^{(-0.099(t+1.188))})$ for females and $FL_t=51.87(1-{\exp}^{(-0.135(t+1.697))})$ for males. Until the age of 3 years, males grew faster than females; however, from the age of 4 years, females grew faster than males. In the future, we want to study the relationship between early growth and water temperature changes in the East Sea.

APPLICATION STUDY OF CHEMOINFOMETRICAL NEAR-INFRARED SPECTROSCOPY IN PHARMACEUTICAL INDUSTRY

  • Otsuka, Makoto;Kato, Fumie;Matsuda, Yoshihisa
    • Proceedings of the Korean Society of Near Infrared Spectroscopy Conference
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    • 2001.06a
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    • pp.2111-2111
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    • 2001
  • A chemoinfometrical method for evaluating the quantitative determination of crystallinity one polymorphs based on fourie-transformed near-infrared (FT-NIR) spectroscopy was established. A direct comparison of the data with the ones collected from using the and compared with the conventional powder X-ray diffraction method was performed. [Method] The pPure a and g forms of indomethacin (IMC) were prepared by reportedusing published methods. Six kinds of standard samples obtained by physically mixing of a and g forms. After the powder X-ray diffraction profiles of samples have been measured, the intensity values were normalized to against the intensity of silicon powder as the as an external standard. The calibration curves for quantification of crystal content were based upon the total relative intensity of four diffraction peaks from of the form g crystal. FT-NIR spectra of six calibration sample sets were recorded 5 times with the NIR spectrometer (BRAN+LUEBBE). Chemoinfometric analysis was performed on the NIR spectral data sets by applying the principal component regression (PCR). [Results] The relation between the actual and predicted polymorphic contents of form g IMC measured using by the X-ray diffraction method shows a good straight linen linear relation., and it has slope of 0.023, an intercept of 0.131 and a correlation coefficient of 0.986. PCR analyses wereis was performed based on normalized NIR spectra sets offer standard samples of known content of IMC g form. IMC. A calibration equation was determined to minimize the root mean square error of the predictionthe prediction. Figure 1 shows a plot of the calibration data obtained by NIR method between the actual and predicted contents of form g IMC. The predicted values were reproducible and had a smaller standard deviation. Figure 2 shows that the plot for the predicted transformation rate (%) of form a IMC to form g as measured by X-ray diffractomeoy against to those as measured by NIR method. The plot has a slope of 1.296, an intercept of 1,109, and a correlation coefficient of 0.992. The line represents a satisfactory correlation between the two predicted values of form g IMC content. Thus NIR spectroscopy is an effective method for the evaluation to the pharmaceutical products of quantitative of polymorph.

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Studies on the humus soil reclaimed by farming for cultivation (화전토양(火田土壤)의 부식(腐植)에 관(關)한 연구(硏究))

  • Kwag, Pan-Ju
    • Applied Biological Chemistry
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    • v.9
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    • pp.153-159
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    • 1968
  • In this paper the auther investigated the chemical properties, process of humification and type of humic acid in soils which were reclaimed by farming for cultivation in Kangwondo. The results obtained in this studies were summarized as follows: 1. General chemical components of these soil were similar to the ordinary soil but C.E.C. and humus contents were found much more 2. Humic acid and fulvic acid which were extracted with NaOH from soil were greater than those of Na-pyrophosphate(Na-p.) and NaF. Hmus contents and PQ% were increased much more in the upper layer than in the lower layer. 3. Degree of humification of humic acid extracted with NaOH. was very similar to those extracted with Na-pyrophosphate. Humification degree of humic acid extracted with NaF was lower than humic acid which were extracted with NaOH and Na-pyrophosphate. But humification degree of humic acid extracted with NaOH was similar to that with Na-pyrophosphate. Humic acid in B soil and the upper layer was higher than A, C soil and the lower layer of soil, in humification degree. 4. Humic acids extracted with NaOH and Na-pyrophosphate from soil were fractionated by Mg into two parts ${\alpha}$ type and ${\beta}$ type humic acid. Humic acids of ${\alpha}$ and ${\beta}$ type extracted with NaOH were higher than these of Na-pyrophosphate in humification degree. In this soil the humification degree of humic acid was not changed during the period of cultivation. 5. ${\alpha}$, ${\beta}$ type humic acid extracted with NaOH were very similar to the humic acid extracted with Na-pyrophosphate in shapes of absorption curves.

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CLASSIFICATION OF MUSCARINIC RECEPTOR SUBTYPES BY OXOMEMAZINE

  • Lee, Shin-Woong-;Woo, Chang-Woo;Kim, Jeung-Gu-
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1994.04a
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    • pp.290-290
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    • 1994
  • The binding characteristic of oxomemazine to muscarinic receptor in the cerebrum, heart, and ileum were compared to those of pirenzepine to investigate whether oxomemazine could classify the muscarinic receptor subtypes. 〔$^3$H〕Quinucl idinyl benzilate(QNB) identified a single class of muscarinic receptors with apparent K$\sub$D/ value of about 60 pM in three tissues. Analysis of the pirenzepine inhibition curve of 〔$^3$H〕QNB binding to cerebral microsome indicated the presence of two receptor subtypes with high (Ki=16 nM, M$_1$-receptor) and low (Ki=400 nM, M$_2$-receptor) affinity for pirenzepine. Oxomemazine also identified two receptor subtypes with high (Ki=84 nM, On-receptor) and low (Ki=1 4 ${\mu}$M, O$\sub$L/-receptor) affinity in rat cerebral microsome, The percentage population of the M$_1$-and M$_2$-receptors to the total receptors were 61 : 39, and those of the O$\^$H/- and O$\sub$L/-receptors 39 : 61, respectively, However, the Hill coefficients of these two drugs for the inhibition of 〔$^3$H〕QNB binding to the heart and ileum were close to unity which indicated that these drugs bound to a uniform population of receptors in these two tissues. The Ki values for the low affinity sites of pirenzepine and oxomemazine in the cerebrum were similar to those of these drugs in the heart ileum. Both pirenzepine and oxomemazine increased K$\sub$D/ value for 〔$^3$H〕QNB without affecting the binding sites concentration and Hill coefficient for the 〔$^3$H〕QNB binding. Oxomemazine had a 10-fold lower affinity at Ma-receptors than at M$_1$-receptors, and pirenzepine a 8-fold lower affinity at O$\sub$L/-receptors than OH-receptors. Analysis of the shal low competition curves of oxomemazine for the H$_1$ receptors and pirenzepine for the O$\sub$L/-receptors yielded that 69% of the M$_1$-receptors were of the O$\sub$H/-receptors and the remaining 31% of the O$\sub$L/-receptors, and that 29% of the O$\sub$L/-receptors were of the M$_1$-receptors and 71% of the M$_2$-receptors. However, M$_2$ for oxomemazine and O$\sub$H/ for pirenzepine were composed of a uniform population. These results suggest that oxomemazine could discriminatethe muscarnic receptor subtypes and may subclassify the M$_1$-receptors into two subtypes.

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Validation of LC-MS/MS Method for Determination of Rabeprazole in Human Plasma : Application of Pharmacokinetics Study (인체 혈장중 라베프라졸의 정량을 위한 LC-MS/MS 분석법 검증 및 단일 용량 투여에 의한 약물동태 연구)

  • Tak, Sung-Kwon;Seo, Ji-Hyung;Ryu, Ju-Hee;Choi, Sang-Joon;Lee, Myung-Jae;Kang, Jong-Min;Lee, Jin-Sung;Hong, Seung-Jae;Yim, Sung-Vin;Lee, Kyung-Tae
    • Journal of Pharmaceutical Investigation
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    • v.39 no.1
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    • pp.73-78
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    • 2009
  • A simple LC-MS/MS method of rabeprazole in human plasma was developed and validated. Rabeprazole and Internal standard (I.S), omeprazole, were extracted from human plasma by liquid liquid extraction, chromatographic separation of rabaprazole in plasma was achieved at $45^{\circ}C$ with a Shiseido UG120 $C_{18}$ column and methanol-10 mM ammonium acetate buffer (pH 9.42 with ammonium water), as mobile phase. Rabeprazole produced a protonated precursor ion [$(M+H)^+$] at m/z 360.10 and corresponding product ion at m/z 242.21. Internal standard produced a protonated precursor ion [$(M+H)^+$] at 346.09 and corresponding product ion at m/z 198.09. This method showed linear response over the concentration range of $1{\sim}500\;ng/mL$ with correalation coefficient greater than 0.99. The lower limit of quantitation (LLOQ) using 0.2 mL plasma was 1 ng/mL, which was sensitive enough for pharmacokinetics studies. The method was specific and validated with a limit of quantitation of 1 ng/mL. The intra-day and inter-day precision and accuracy were acceptable for all samples including the LLOQ. The applicability of the method was demonstrated by analysis of plasma after administration of a single 10 mg dose to 36 healthy subject. From the plasma rabeprazole concentration versus time curves, the mean $AUC_t$ (The area under the plasma concentration-time curve from time 0 to 12 hr ) was $691.36{\pm}321.88\;ng{\cdot}hr/mL$, $C_{max}$ (maximum plasma drug concentration) of $353.21{\pm}131.52\;ng/mL$ reached $3.4{\pm}1.1\;hr$ after adiministration. The mean biological half-life of rabeprazole was $1.37{\pm}0.75\;hr$. Based on the results, this simple method could readily be used in pharmacokinetics studies.

Concentration Variation of Atmospheric Radon and Gaseous Pollutants Related to the Airflow Transport Pathways during 2010~2015 (대기 라돈 및 기체상 오염물질의 기류 이동경로별 농도변화: 2010~2015년 측정)

  • Song, Jung-Min;Kim, Ki-Ju;Bu, Jun-Oh;Kim, Won-Hyung;Kang, Chang-Hee;Chambers, S.
    • Journal of Korean Society for Atmospheric Environment
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    • v.34 no.2
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    • pp.321-330
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    • 2018
  • Concentrations of the atmospheric radon and gaseous pollutants were measured at the Gosan site on Jeju Island from 2010 to 2015, in order to observe their time-series variation characteristics and examine the concentration change related to the airflow transport pathways. Based on the realtime monitoring of the atmospheric radon and gaseous pollutants, the daily mean concentrations of radon ($^{222}Rn$) and gaseous pollutants($SO_2$, CO, $O_3$, $NO_x$) were $2,400mBq\;m^{-3}$ and 1.3, 377.6, 41.1, 3.9 ppb, respectively. On monthly variations of radon, the mean concentration in October was the highest as $3,033mBq\;m^{-3}$, almost twice as that in July ($1,452mBq\;m^{-3}$). The diurnal variation of radon concentration shows bimodal curves at early morning (around 7 a.m.) and near midnight, whereas its lowest concentration was recorded at around 3 p.m. Several gaseous pollutants($SO_2$, CO, $NO_x$) showed a similar seasonal variation with radon concentration as high in winter and low in summer, whereas the $O_3$ concentrations had a bit different seasonal trend. According to the cluster back trajectory analysis, the frequencies of airflow pathways moving from continental North China, East China, Japan and the East Sea, the Korean Peninsula, and North Pacific Ocean routes were 36, 37, 10, 13, and 4%, respectively. When the airflow were moved to Jeju Island from continental China, the concentrations of radon and gaseous pollutants were relatively high. On the other hand, when the airflows were moved from North Pacific Ocean and East Sea, their concentrations were much lower than those from continental China.

Gene Expression Biodosimetry: Quantitative Assessment of Radiation Dose with Total Body Exposure of Rats

  • Saberi, Alihossein;Khodamoradi, Ehsan;Birgani, Mohammad Javad Tahmasebi;Makvandi, Manoochehr
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.18
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    • pp.8553-8557
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    • 2016
  • Background: Accurate dose assessment and correct identification of irradiated from non-irradiated people are goals of biological dosimetry in radiation accidents. Objectives: Changes in the FDXR and the RAD51 gene expression (GE) levels were here analyzed in response to total body exposure (TBE) to a 6 MV x-ray beam in rats. We determined the accuracy for absolute quantification of GE to predict the dose at 24 hours. Materials and Methods: For this in vivo experimental study, using simple randomized sampling, peripheral blood samples were collected from a total of 20 Wistar rats at 24 hours following exposure of total body to 6 MV X-ray beam energy with doses (0.2, 0.5, 2 and 4 Gy) for TBE in Linac Varian 2100C/D (Varian, USA) in Golestan Hospital, in Ahvaz, Iran. Also, 9 rats was irradiated with a 6MV X-ray beam at doses of 1, 2, 3 Gy in 6MV energy as a validation group. A sham group was also included. After RNA extraction and DNA synthesis, GE changes were measured by the QRT-PCR technique and an absolute quantification strategy by taqman methodology in peripheral blood from rats. ROC analysis was used to distinguish irradiated from non-irradiated samples (qualitative dose assessment) at a dose of 2 Gy. Results: The best fits for mean of responses were polynomial equations with a R2 of 0.98 and 0.90 (for FDXR and RAD51 dose response curves, respectively). Dose response of the FDXR gene produced a better mean dose estimation of irradiated "validation" samples compared to the RAD51 gene at doses of 1, 2 and 3 Gy. FDXR gene expression separated the irradiated rats from controls with a sensitivity, specificity and accuracy of 87.5%, 83.5% and 81.3%, respectively, 24 hours after dose of 2 Gy. These values were significantly (p<0.05) higher than the 75%, 75% and 75%, respectively, obtained using gene expression of RAD51 analysis at a dose of 2 Gy. Conclusions: Collectively, these data suggest that absolute quantification by gel purified quantitative RT-PCR can be used to measure the mRNA copies for GE biodosimetry studies at comparable accuracy to similar methods. In the case of TBE with 6MV energy, FDXR gene expression analysis is more precise than that with RAD51 for quantitative and qualitative dose assessment.

Simultaneous Determination of B Group Vitamins in Supplemented Food Products by High Performance Liquid Chromatography-Diode Array Detection

  • Suh, Joon-Hyuk;Yang, Dong-Hyug;Lee, Byung-Kyu;Eom, Han-Young;Kim, Un-Yong;Kim, Jung-Hyun;Lee, Hye-Yeon;Han, Sang-Beom
    • Bulletin of the Korean Chemical Society
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    • v.32 no.8
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    • pp.2648-2656
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    • 2011
  • A simple HPLC-DAD method was developed and validated to determine B group vitamin content (thiamine, riboflavin, nicotinamide, pantothenic acid, pyridoxine and folic acid) in supplemented food samples, i.e., infant formula, cereal, low-calorie food, a multi-vitamin pill and a vitamin drink. In this study, the most significant advantages were simultaneous determination of the six B group vitamins in various food matrices and a small number of sample treatment steps that required only an organic solvent, acetonitrile. Moreover, this method prevents reduction of column durability, because the mobile phase does not contain ion-pairing reagents. Analytes were separated on a Develosil RPAQUEOUS $C_{30}$ (4.6 mm ${\times}$ 250 mm, 5 ${\mu}M$ particle size) column with a gradient elution of acetonitrile and 20 mM phosphate buffer (pH 3.0) at a flow rate between 0.8 and 1.0 mL/min. Detection was performed at 275 nm, except for that of pantothenic acid (205 nm). The calibration curves for all six vitamins showed good linearity with correlation coefficients ($r^2$) higher than 0.995. The developed method was validated with respect to linearity, intra- and inter-day accuracy and precision, limit of quantification (LOQ), recovery and stability. The method showed good precision and accuracy, with intra- and inter-assay coefficients of variation less than 15% at all concentrations. The recovery was carried out according to the standard addition procedure, with yields ranging from 89.8 to 104.4%. This method was successfully applied to the determination of vitamin B groups in supplemented food products.

Effects of processing method on the pharmacokinetics and tissue distribution of orally administered ginseng

  • Chen, Jianbo;Li, Meijia;Chen, Lixue;Wang, Yufang;Li, Shanshan;Zhang, Yuwei;Zhang, Lei;Song, Mingjie;Liu, Chang;Hua, Mei;Sun, Yinshi
    • Journal of Ginseng Research
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    • v.42 no.1
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    • pp.27-34
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    • 2018
  • Background: The use of different methods for the processing of ginseng can result in alterations in its medicinal properties and efficacy. White ginseng (WG), frozen ginseng (FG), and red ginseng (RG) are produced using different methods. WG, FG, and RG possess different pharmacological properties. Methods: WG, FG, and RG extracts and pure ginsenosides were administered to rats to study the pharmacokinetics and tissue distribution characteristics of the following ginsenosides-DRg1, Re, Rb1, and Rd. The concentrations of the ginsenosides in the plasma and tissues were determined using UPLC-MS/MS. Results: The rate and extent of absorption of Rg1, Re, Rb1, and Rd appeared to be affected by the different methods used in processing the ginseng samples. The areas under the plasma drug concentration-time curves (AUCs) of Rg1, Re, Rb1, and Rd were significantly higher than those of the pure ginsenosides. In addition, the AUCs of Rg1, Re, Rb1, and Rd were different for WG, FG, and RG. The amounts of Rg1, Re, Rd, and Rb1 were significantly (p < 0.05) higher in the tissues than those of the pure ginsenosides. The amounts of Re, Rb1, and Rd from the RG extract were significantly higher than those from the WG and FG extracts in the heart, lungs, and kidneys of the rats. Conclusion: Our results show that the use of different methods to process ginseng might affect the pharmacokinetics and oral bioavailability of ginseng as well as the tissue concentrations of Rg1, Re, Rd, and Rb1.