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Effect of Gongjindan-gamibang on the Pharmacokinetics Profiles of Sorafenib in Male SD Rats (2) - Single Oral Combination Treatment of Sorafenib 50mg/kg with Gongjindan-gamibang 100 mg/kg, 3.5hr-intervals with 7-day Repeated Treatment -

  • Lee, Chang Hyeong;Kim, Seung Mo;Kang, Su Jin;Park, Soo Jin;Song, Chang Hyun;Han, Chang Hyun;Lee, Young Joon;Ku, Sae Kwang
    • Journal of Society of Preventive Korean Medicine
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    • v.19 no.1
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    • pp.145-159
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    • 2015
  • Objective : In the previous study, co-administration of Gongjindan-gamibang (GJD) with sorafenib increased oral bioavailability of sorafenib through augment the absorption, therefore, the effects of GJD co-administration on the pharmacokinetics of sorafenib were observed after single and 7-day repeated oral co-administration with 3.5 hr-intervals in the present study. Method : After 50 mg/kg of sorafenib treatment, GJD 100 mg/kg was administered with 3.5 hr-intervals. The plasma were collected at 30 min before administration, 30 min, 1, 2, 3, 4, 6, 8 and 24 hrs after end of first and last 7th sorafenib treatment, and plasma concentrations of sorafenib were analyzed using LC-MS/MS methods. PK parameters of sorafenib ($T_{max}$, $C_{max}$, AUC, $t_{1/2}$ and $MRT_{inf}$) were analysis as compared with sorafenib single administered rats. Results : GJD markedly inhibited the absorption of sorafenib, from 1 hr to 24 hrs after end of first 3.5 hr-interval co-administration, the $C_{max}$ (-43.27%), $AUC_{0-t}$ (-56.29%) and $AUC_{0-inf}$ (-66.70%) of sorafenib in co-administered rats were dramatically decreased as compared with sorafenib single treated rats. However, GJD significantly increased the absorption of sorafenib, from 4 hr to 8 hrs after end of last 7th 3.5 hr-interval co-administration, the $AUC_{0-t}$ (34.08%) and $AUC_{0-inf}$ (37.31%) of sorafenib in co-administered rats were dramatically increased as compared with sorafenib single treated rats. Conclusion : Although GJD decreased the oral bioavailability of sorafenib through inhibition of gastrointestinal absorptions after end of first 3.5 hr-interval co-administration, it is observed that GJD increases the oral bioavailability of sorafenib as facilitated the absorption after end of last 7th repeated co-administration. Hence, the co-administration of GJD and sorafenib should be avoided in the combination therapy of sorafenib with GJD on anticancer therapy.

Identification and Quantification of Glucosinolates in Rapeseed (Brassica napus L.) Sprouts Cultivated under Dark and Light Conditions

  • Lee, Min-Ki;Arasu, Mariadhas Valan;Chun, Jin-Hyuk;Seo, Jeong Min;Lee, Ki-Teak;Hong, Soon-Taek;Kim, In Ho;Lee, Yong-Hwa;Jang, Young-Seok;Kim, Sun-Ju
    • Korean Journal of Environmental Agriculture
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    • v.32 no.4
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    • pp.315-322
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    • 2013
  • BACKGROUND: This study was performed for the identification and quantification of glucosinolate (GSL) contents in seven varieties of rapeseed (Brassica napus L.) sprouts cultivated under dark and light conditions. METHODS AND RESULTS: Crude glucosinolates (GSLs) were desulfated by treating with aryl sulfatase and purified using diethylaminoethyl sepharose (DEAE) anion exchange column. Individual GSLs were quantified using high-performance liquid chromatography (HPLC) with electrospray ionization-tandem mass spectrometry (ESI-MS/MS). Eleven GSLs including six aliphatic (progoitrin, sinigrin, glucoalyssin, gluconapoleiferin, gluconapin, and glucobrassicanapin), four indolyl (4-hydroxyglucobrassicin, glucobrassicin, 4-methoxyglucobrassicin, and neoglucobrassicin) and one aromatic (gluconasturtiin) were identified based on the fragmentation patterns of MS spectrum. Aliphatic GSLs were noted as the predominant group with average 85.2% of the total contents. The most abundant GSLs were progoitrin which was ranged at $8.14-118.68{\mu}mol/g$ dry weight (DW). The highest total GSL amounts were documented in 'Hanra' ($146.02{\mu}mol/g$ DW) under light condition and 'Mokpo No. 68' ($86.67{\mu}mol/g$ DW) in dark condition, whereas the lowest was in 'Tamra' (30.13 and $14.50{\mu}mol/g$ DW) in both conditions. The sum of aliphatic GSLs attributed > 80% in all varieties, except 'Tamra' (67.7% and 64.9% in dark and light conditions, respectively) in the total GSL accumulation. Indolyl GSLs were ranged $2.41-15.73{\mu}mol/g$ DW, accounted 2.78-33.6% of the total GSLs in rapeseed varieties. CONCLUSION(S): These results provide valuable information regarding potential beneficial GSL contents individually. This study attempts to contribute to knowledge of the nutritional properties of the different varieties of rapeseed plants. These results may be useful for the evaluation of dietary information.

Estimation of the Daily Human Intake of Acrylamide (AA) Based on Urinary N-acetyl-S-(2-carbamoylethyl)-cysteine (AAMA) and the Contribution of Dietary Habits in South Korean Adults (요중 AAMA에 의한 한국 성인 아크릴아마이드(AA)의 하루섭취량 추정 및 기여 식습관에 대한 분석)

  • LEE, Jin-Heon;LEE, Kee-Jae;KANG, Hee-Sook
    • Journal of Environmental Health Sciences
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    • v.42 no.4
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    • pp.235-245
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    • 2016
  • Objectives: This study estimated the adult Korean daily intake of acrylamide (AA) and investigated its relationship with demographic, lifestyle and dietary habits by using urinary concentrations of N-acetyl-S-(2-carbamoylethyl)-cysteine (AAMA). Methods: Human data (n=1870) was collected in a nationwide cross-sectional biomonitoring program representing the population (18-69 years) residing in South Korea. Urinary AAMA was analyzed with a LC-MS/MS system. Daily intakes of AA were estimated using mass daily AAMA, which was calculated through urinary AAMA concentration and daily creatinine excretion. Statistical analysis was performed with SAS procedures for calculating geometric means, confidence intervals and the exponentiated beta coefficient of multiple linear regressions. Results: Daily intake of AA was estimated at $0.475{\mu}g/kg$ body weight (BW) per day (95% confidence interval (CI): 0.447-0.503). In the case of current smokers, AA intake was $0.957{\mu}g/kg$ BW per day (95% CI: 0.847-1.067), which was significantly higher than that of former smokers and never smoked (p<0.0001). The strong affecting factors were age (95% CI: 0.68-1.14; p=0.0180), education level (95% CI: 1.05-1.42; p=0.0163), body mass index (BMI) (95% CI: 1.00-1.82; p<0.0001), and smoking status (95% CI: 0.97-3.05; p<0.0001). Korean dietary habits increasing AA intake were coffee (p=0.0005), cup noodles (p=0.0010) and canned foods (p=0.0005). Meanwhile, foods decreasing AA intake were fresh fruit (p=0.0076), cooked beef (p=0.0335) and cooked pork (p=0.0147). Conclusion: The Korean daily intake of AA in adults was estimated to be similar with those found in developed countries. The factors increasing daily AA intake were coffee, cup noodles and canned foods, and decreasing factors were fresh fruit, cooked beef and cooked pork.

A Diagnostic Algorithm after Newborn Screening for 21-hydroxylase Deficiency (선천성 부신 과형성증(21-hydroxylase 결핍)의 신생아 선별 검사 후 진단 알고리즘)

  • Cho, Sung Yoon;Ko, Jung Min;Lee, Kyung-A
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.16 no.2
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    • pp.70-78
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    • 2016
  • 21-hydroxylase deficiency (21-OHD), most common form of congenial adrenal hyperplasia, is categorized into classical forms, including the salt-wasting (SW) and the simple virilizing (SV) types, and nonclassical (NC) forms based on the severity of the disease. Newborn screening for 21-OHD has been performed in Korea since 2006. $17{\alpha}$-hydroxyprogesterone (17-OHP) is a marker for 21-OHD and is measured using a radioimmunoassay or a fluoroimmunoassay. Premature and low birth weight infants are likely to give false positive 17-OHP findings, therefore, cutoff values for these infants should be determined based on gestational weeks or birth weight. ACTH simulation test is helpful when the 17-OHP shows equivocal increase, and it is gold standard for diagnosis of NC type. Recently, liquid chromatography linked with tandem mass spectrometry was developed for rapid, highly specific, and sensitive analysis of multiple analytes. Molecular analysis of CYP21A2 is useful for confirming diagnosis of mild SV or NC type, predicting prognoses, and genetic counseling. In order to make newborn screening for 21-OHD more efficient, early detection of boy with SW type, early determination of girl with ambiguous genitalia, detection of NC type, and overcoming of false positive in premature and low birth weight infants should be considered. Above all, early treatment should be started when the patient is suspected as having 21- OHD clinically before confirming the diagnosis to prevent adrenal crisis. Here, author reviewed recent articles of guideline and proposed guideline for 21-OHD.

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Attenuation of pneumoperitoneum-induced hypertension by intra-peritoneal lidocaine before pneumoperitoneum in laparoscopic cholecystectomy (복강경 담낭절제술 시 공기배증 전에 주입한 복강 내 lidocaine의 공기배증 후 혈압상승 완화효과)

  • Song, Sun Ok;Lee, Hae Mi;Yun, Sung Soo;Yu, Hwarim;Shim, Soo Young;Kim, Heung Dae
    • Journal of Yeungnam Medical Science
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    • v.33 no.2
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    • pp.90-97
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    • 2016
  • Background: We have previously found that intra-peritoneal lidocaine instillation before pneumoperitoneum attenuates pneumoperitoneum-induced hypertension. Whether this procedure alters patient's hemodynamic status during operation should be determined for clinical application. This study elucidated the possible mechanism of the attenuation of the pneumoperitoneum-induced hypertension by intra-peritoneal lidocaine before pneumoperitoneum. Methods: Thirty-four patients underwent laparoscopic cholecystectomy (LC) were randomly allocated into two groups. After induction of general anesthesia, 200 mL of 0.2% lidocaine (lidocaine group, n=17), or normal saline (control group, n=17) were sub-diaphragmatically instilled 10 minutes before pneumoperitoneum. The changes in systolic blood pressure, heart rate, central venous pressure, stroke volume, cardiac output, and systemic vascular resistance were compared between the groups. The number of analgesics used during post-operative 24 h was compared. Results: Systolic blood pressure was elevated during pneumoperitoneum in both groups (p<0.01), but the degree of elevation was significantly reduced in the lidocaine group than in the control (p<0.01). However, stroke volume and cardiac output were decreased and systemic vascular resistance was increased after induction of pneumoperitoneum (p<0.05) without statistical difference between two groups. The number of analgesics used was significantly reduced in the lidocaine group (p<0.01). Conclusion: These data suggest that intra-peritoneal lidocaine before pneumoperitoneum does not alter patient's hemodynamics, and attenuation of pneumoperitoneum-induced hypertension may be the consequence of reduced intra-abdominal pain rather than the decrease of cardiac output during pneumoperitoneum. Therefore, intra-peritoneal lidocaine instillation before pneumoperitoneum is a useful method to manage an intraoperative pneumoperitoneum-induced hypertension and to control postoperative pain without severe detrimental hemodynamic effects.

Effects of Sodium Butyrate on the Biosynthesis of Sphingolipids in HT29, a Human Colon Cancer Cell Line (Sodium Butyrate 처리가 대장암 세포주인 HT29 Cell의 Sphingolipid 생합성에 미치는 영향)

  • 김희숙
    • Journal of Life Science
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    • v.9 no.2
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    • pp.160-168
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    • 1999
  • Butyrate is one of the short-chain fatty acids that are present in the colon of mammals in millimolar concentration as a result of microbial anaerobic fermentation of dietary fiber, undigested starch, and proteins. In this study, sodium butyrate was examined in HT29 cell, human colonic cancer cell line, on cell viability, alkaline phosphatase activity, PLC-${\gamma}$1 expression and complex sphingolipid biosynthesis. Treatment with butyrate showed that the decrease of cell adhesion and viability was time-dependent. Sodium butyrate also induced to increase the activity of alkaline phosphatase which is a differentiation marker enzyme and decrease the expression of PLC-${\gamma}$1. Biosynthesis of sphingomyelin and galactosylceramide by butyrate treatment were decreased so fast but ceramide was increased 680dpm/mg protein% more than untreated group on first day and then decreased fast. In addition, acid ceramidase and neutral ceramidase activity were inhibited early stage by sodium butyrate. These results suggest that sodium butyrate causes cell differentiation or cell growth arrest of HT29 cell accompanied by early increase of ceramide content and alkaline phosphatase activity and decrease of galactosylceramide content and PLC-r1 expression.

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Determination of individual sugars in different varieties of persian grape using Near Infrared spectroscopy

  • Kargosha, Kazem;Azad, Jila;Lary, Abas Motamed
    • Proceedings of the Korean Society of Near Infrared Spectroscopy Conference
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    • 2001.06a
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    • pp.1527-1527
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    • 2001
  • Glucose, fructose and sucrose being the main sugars that can be found in natural fruit juice. Many instrumental methods, such as GC, LC, electrochemical or spectrometric methods provide information about both the total content of sugars and the specific concentration of each carbohydrate[1]. The simplicity of sample handling and measurement in the near IR(NIR) wavelength region, which allows the use of long pathlength, optical glass cells and optical fibers, makes NIR a good alternative for sugar determination [2]. In the present study, six varieties of persian grapes were harvested at intervals through august to october and analysed for sugars by NIR. The results were processed by principal component regression (PCR) and partial least squares (PLS) analysis. Sample juice was prepared by squeezing through gauze from crashed grape. This solution was treated by zinc ferrocyanide prior to analysis in order to eliminate colored compounds and all optically active nonsugar substances. For glucose and fructose the most characteristic wavelengths were 1456nm corresponding to the first harmonic O-H stretching and the second at 2062nm corresponding to O-H stretching and deformation; secondary characteristic combination bands were also seen at 2265 nm (O-H and C-C stretching) and at 2240 nm (C-H and C-C stretching). However these spectra were taken over a wavelength range from 1100-2500nm at room temperature of 25-$30^{\circ}C$. To test the accuracy of the described procedure, samples of six varieties of grape were analysed by the proposed NIR and a standard method[2]. Good agreement were found between these two sets of the results. To perform the recovery studies , samples of grape juices previously analysed by the proposed method, were spiked with known amounts of each individual sugars and then analysed again. Relative standard deviations varied from 1.4 to 1.8% for six independent measurements of individual and total sugar concentration. In the analysis of real and synthetic samples, precise and accurate results were obtained , providing accuracy errors lower than 1.9% in all cases. Average recoveries of ${97}{\pm}{4%}$ for total sugar and between ${95}{\pm}{5%}$ and ${99}{\pm}{2%}$ for sing1e sugars demonstrate the applicability of the methodology developed to the direct analysis of grape Juice.

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Autophagy Inhibitor, 3-Methyladenine, Reduces Preimplantation Development and Blastocyst Qualities in Pigs

  • Park, Jin-Mo;Min, Sung-Hun;Hong, Joo-Hee;Lee, E-Nok;Son, Hyeong-Hoon;Park, Hum-Dai;Koo, Deog-Bon
    • Reproductive and Developmental Biology
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    • v.35 no.3
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    • pp.287-294
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    • 2011
  • Autophagy is a process of intracellular bulk protein degradation, in which the accumulated proteins and cytoplasmic organelles are degraded. It plays important roles in cellular homeostasis, apoptosis, and development, but its role during early embryo development remains contentious. Therefore, in the present study, we investigated the effects of 3-methyladenine (3-MA) on early embryonic development in pigs, we also investigated several indicators of developmental potential, including mitochondrial distribution, genes expressions (autophagy-, apoptosis- related genes), apoptosis and ER-stress, which are affected by 3-MA. After in vitro maturation and fertilization, presumptive pig embryos were cultured in PZM-3 medium supplemented with 3-MA for 2 days at $39^{\circ}C$ 5% $CO_2$ in air. Developmental competence to the blastocyst stage in the presence of 3-MA was gradually decreased according to increasing concentration. Thus, all further experiments were performed using 2 mM 3-MA. Blastocysts that developed in the 3-MA treated group decreased LC3-II intensity and expressions of autophagy related genes than those of the untreated control, resulting in down-regulates the autophagy. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) showed that the number of containing fragmented DNA at the blastocyst stage increased in the 3-MA treated group compared with control ($6.0{\pm}1.0$ vs $3.3{\pm}0.6$, p<0.05). Also, the expression of the pro-apoptotic gene Bax increased in 3-MA treated group, whereas expression of the anti-apoptotic gene Bcl-XL decreased. Mito Tracker Green FM staining showed that blastocysts derived from the 3-MA treated group had lower mitochondrial integrity than that of the untreated control, resulting in decrease the embryonic qualities of preimplantation porcine blastocysts. Then, the expression of the spliced form of pXBP-1 product (pXBP-1s) increased in 3-MA treated group, resulting increase of ER-stress. Taken together, these results indicate that inhibition of autophagy by 3-MA is closely associated with apoptosis and ER-stress during preimplantation periods of porcine embryos.

Determination of Cyhalofop-butyl and its Metabolite in Water and Soil by Liquid Chromatography (LC를 이용한 물과 토양 중 Cyhalofop-butyl과 대사물질의 분석)

  • Hem, Lina;Choi, Jeong-Heui;Liu, Xue;Khay, Sathya;Shim, Jae-Han
    • The Korean Journal of Pesticide Science
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    • v.12 no.4
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    • pp.315-322
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    • 2008
  • In this study, a simple, effective, and sensitive method has been developed for the quantitative residue analysis of cyhalofop-butyl and its metabolite cyhalofop acid in water and soil when kept under laboratory conditions. The content of cyholofop-butyl and cyhalofop acid in water and soil was analyzed by first purifying the compounds through liquid-liquid extraction and partitioning followed by Silica gel (adsorption) chromatography. Upon the completion of the purification step the residual levels were monitored through high-performance liquid chromatography (HPLC) using a UV absorbance detector. The recoveries of cyhalofop-butyl from three replicates spiked at two different concentrations ranged from 82.5 to 100.0% and from 66.7 to 97.9% in water and soil, respectively. The limit of detection and minimum detection level of cyhalofop-butyl in water and soil was 0.02 ppm and 10 ng, respectively. The recoveries of cyhalofop acid ranged from 80.7 to 104.8% in water and from 76.9 to 98.1 % in soil. The limit of detection of cyhalofop acid was 0.005 ppm in water and 0.01 ppm in soil, while the minimum detection level was 2 ng both in water and soil. The half-live of cyhalofop-butyl was 4.14 and 6.6 days in water and soil, respectively. The method was successfully applied to evaluate cyhalofop-butyl residues in water and soil applied aj. 30% emulsion, oil in water (EW) product.

The Effect of Bonding Resin on Bond Strength of Dual-Cure Resin Cements (접착레진의 부가도포가 레진 시멘트의 결합강도에 미치는 영향에 대한 연구)

  • Kim, Duck-Su;Park, Sang-Hyuk;Choi, Gi-Woon;Choi, Kyung-Kyu
    • Restorative Dentistry and Endodontics
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    • v.32 no.5
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    • pp.426-436
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    • 2007
  • The objective of this study is to evaluate the effect of an additional application of bonding resin on the bond strength of resin luting cements in both the light-cure (LC) and self-cure (SC) modes by means of the ${\mu}TBS$ tests. Three combinations of One-Step Plus with Choice, Single Bond with Rely X ARC, and One-Up Bond F with Bistite II were used. D/E resin and Pre-Bond resin were used for the additional application. Twelve experimental groups were made. Three mandibular $3^{rd}$ molars were used in each group. Indirect composite blocks were cemented on the tooth surface. $1\;{\times}\;1\;mm^2$ dentin-composite beam for ${\mu}TBS$ testing were made and tested. When total-etching dentin adhesives were used, an additional application of the bonding resin increased the bond strength (P < 0.05). However, this additional application didn't influence the bond strength of self-etching dentin adhesives (P > 0.05). In conclusion, the results suggest that an additional application of the bonding resin increases bond strength and enhances quality of bonding when using total-etching dentin adhesives.