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Effect of TSHAC on Human Cytochrome P450 Activity, and Transport Mediated by P-Glycoprotein

  • Im, Yelim;Kim, Yang-Weon;Song, Im-Sook;Joo, Jeongmin;Shin, Jung-Hoon;Wu, Zhexue;Lee, Hye Suk;Park, Ki Hun;Liu, Kwang-Hyeon
    • Journal of Microbiology and Biotechnology
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    • v.22 no.12
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    • pp.1659-1664
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    • 2012
  • TSAHC [4'-(p-toluenesulfonylamido)-4-hydroxychalcone] is a promising antitumorigenic chalcone compound, especially against TM4SF5 (four-transmembrane L6 family member 5)-mediated hepatocarcinoma. We evaluated the potential of TSAHC to inhibit the catalytic activities of nine cytochrome P450 isoforms and of P-glycoprotein (P-gp). The abilities of TSAHC to inhibit phenacetin O-deethylation (CYP1A2), coumarin 6-hydroxylation (CYP2A6), bupropion hydroxylation (CYP2B6), amodiaquine N-deethylation (CYP2C8), diclofenac 4-hydroxylation (CYP2C9), omeprazole 5-hydroxylation (CYP2C19), dextromethorphan O-demethylation (CYP2D6), chlorzoxazone 6-hydroxylation (CYP2E1), and midazolam 1'-hydroxylation (CYP3A) were tested using human liver microsomes. The P-gp inhibitory effect of TSAHC was assessed by [$^3H$]digoxin accumulation in the LLCPK1-MDR1 cell system. TSAHC strongly inhibited CYP2C8, CYP2C9, and CYP2C19 isoform activities with $K_i$ values of 0.81, 0.076, and $3.45{\mu}M$, respectively. It also enhanced digoxin accumulation in a dose-dependent manner in the LLCPK1-MDR1 cells. These findings indicate that TSAHC has the potential to inhibit CYP2C isoforms and P-gp activities in vitro. TSAHC might be used as a nonspecific inhibitor of CYP2C isoforms based on its negligible inhibitory effect on other P450 isoforms such as CYP1A2, CYP2A6, CYP2B6, CYP2D6, CYP2E1, and CYP3A.

Effects of Fly Ash and Gypsum Mixture on Reducing Phosphorus Loss from Paddy Soil (논 토양에서 석탄회와 석고의 혼합제를 활용한 인산유출 저감)

  • Lee, Yong-Bok;Lee, Seul-Bi;Oh, Ju-Hwan;Lee, Chang-Hoon;Hong, Chang-Oh;Kim, Pil-Joo
    • Korean Journal of Environmental Agriculture
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    • v.27 no.1
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    • pp.66-71
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    • 2008
  • Phosphorus transfer from agricultural soils to surface waters is an important environmental issue. Fly ash and phospho-gypsum which are industrial by-product were investigated as a means of reducing dissolved phosphorus in arable soil. To determine the optimum mixing ratio of fly ash(FA) and phospho-gypsum(PG) for reducing dissolved reactive P(DRP) in soil, various mixture ratio of FA and PG were mixed with two soil. The DRP content and pH in soils were analysed after 3 weeks incubation under flooding condition. Although DRP content in soils was significantly decreased by FA-PG mixture compared with control, there were no significant difference among the FA and PG mixture ratio of 75:25, 50:50, and 25:75. The mixture of 75% FA and 25% PG was selected for field test. A field experiment was carried out to evaluate the reducing DRP content in paddy soil to which 0(NPK), 20(FG 20), 40(FG 40), and 60(FG 60) Mg $ha^{-1}$ of the mixture were applied. The DRP content was reduced by 31% at the application rate of 60 Mg $ha^{-1}$. In contrast to deceasing DRP, Ca-P content increased significantly with the mixture application rate. After rice harvesting, available $SiO_2$, P, and exchangeable Ca content in soil increased significantly with application rate due to high content of Si, P, and Ca in the mixture. Mixtures of fly ash and gypsum should reduce P loss from paddy soil and increase soil fertility.

Effects of Glucose and Inorganic Phosphate on the Development of Rat 8-Cell Embryos In Vitro (Glucose와 Inorganic Phosphate가 Rat 8-세포기 난자의 체외배양에 미치는 영향)

  • 이홍미;진동일
    • Korean Journal of Animal Reproduction
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    • v.20 no.3
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    • pp.251-258
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    • 1996
  • This study was designed to evaluate the potential inhibitory effects of glucose (5.56 mM vs. 0 mM) and/or phosphate (potassium phosphate, 1.19 mM vs. 0 mM) on the in vitro devel-opment of rat 8-cell embryos (n=345 embryos from 36 mature rats). Evaluation of embryos at 48 h for developmental stage (STG) indicated that 37% (31/84), 70% (64/91), 69% (59/85), and 77% (67/85) developed to the blastocyst stage in media with glucose+phosphate, glucose only, phosphate only, and no glucose or phosphate, respectively. Embryo development (2.90${\pm}$0.097 for STG) in medium with glucose + phosphate was significantly reduced (P<0.001), while no significant differences were observed between all other media (3.4~3.5${\pm}$0.093-0.097 for STG). Evaluation of embryos for final cell number (FCN) indicated that the greatest number of cells (nuclei) resulted in medium with glucose alone (29.3${\pm}$0.97 cells, P<0.001). No significant differences were observed for FCN for the remaining three media (l7.5${\pm}$1, 04 cells, 18.6${\pm}$1.Ol cells, and 19.8${\pm}$1.01 cells for glucose+phosphate, phosphate only, and no glucose or phosphate, respectively). Our results suggest that glucose and phosphate together exert an inhibitory effect on 8-cell rat embryo development, while glucose alone was beneficial, yielding greater numbers of cells per embryo.

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Studies on the Developmental Rate of Oocyter Obtained fly Intracytoplasmic Sperm Injection with Epididymal Spermatozoa in Domestic Dogs (개 난자에 부고환 정자로 ICSI후 배양하였을 때 체외발생율에 관한 연구)

  • 김상근;이동수;이만희
    • Korean Journal of Animal Reproduction
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    • v.26 no.2
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    • pp.105-110
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    • 2002
  • The objective of this study was to determine the developmental competence of in vitro matured oocytes after intracytoplasmic sperm injection(ICSI) with epididymal spermatozoa. The ovaries were obtained from slaughtered small species dogs. Oocytes matured in vitro for 24 hrs were fertilized by ICSI with epididymal spermatozoa. After ICSI, one group of oocytes was activated with 2.0 mM dimethylaminopurine or 7% ethanol for 5 min. and second group was not activated. The follicular oocytes were cultured in synthetic oviductal fluid(SOF) and TCM-199 medium containing hormones and 10% FCS for 24~48 hrs in a incubator with 5% $CO_2$ in air at 38.5$^{\circ}C$. 1. Results of IVM showed that the percentage of oocytes reaching MII after 24 h and 48 hrs of incubation were significantly higher(p<0.05) after culture with 48 hrs(9/30, 30.0%) than that after culture with 24hrs(a/30, 26.7%). 2. Results of IVM showed that the percentage of oocytes reaching MII after 48 hrs of incubation were significantly higher(p<0.05) after culture with SOF media(10/30, 30.3%) than TCM-199 media (7/30, 23.3%). 3. The rate of cleavaged embryos to blastocyst obtained by ICSI treated activation oocytes was significantly higher(p<0.05) than that of nonactivation oocytes(5/16, 25.0% vs 1/13, 5.0%). 4. The rates of development of cleavaged embryos to blastocyst obtained by ICSI treated sperm of fresh, epididymal and frozen-thawed epididymal were 8/18(44.43%), 5/16(31.3%), 2/14(14.3%), respectively. and these values of frozen-thawed epididymal sperm injection were lower than fresh sperm injection.

Generation of $CD2^+CD8^+$ NK Cells from c-$Kit^+$ Bone Marrow Cells in Porcine

  • Lim, Kyu-Hee;Han, Ji-Hui;Roh, Yoon-Seok;Kim, Bum-Seok;Kwon, Jung-Kee;You, Myoung-Jo;Han, Ho-Jae;Ejaz, Sohail;Kang, Chang-Won;Kim, Jong-Hoon
    • The Korean Journal of Physiology and Pharmacology
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    • v.16 no.3
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    • pp.167-174
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    • 2012
  • Natural killer (NK) cells provide one of the initial barriers of cellular host defense against pathogens, in particular intracellular pathogens. Because bone marrow-derived hematopoietic stem cells (HSCs), lymphoid protenitors, can give rise to NK cells, NK ontogeny has been considered to be exclusively lymphoid. Here, we show that porcine c-$kit^+$ bone marrow cells (c-$kit^+$ BM cells) develop into NK cells in vitro in the presence of various cytokines [interleukin (IL)-2, IL-7, IL-15, IL-21, stem cell factor (SCF), and fms-like tyrosine kinase-3 ligand (FLT3L)]. Adding hydrocortisone (HDC) and stromal cells greatly increases the frequency of c-$kit^+$ BM cells that give rise to $CD2^+CD8^+$ NK cells. Also, intracellular levels of perforin, granzyme B, and NKG2D were determined by RT-PCR and western blotting analysis. It was found that of perforin, granzyme B, and NKG2D levels significantly were increased in cytokine-stimulated c-$kit^+$ BM cells than those of controls. And, we compared the ability of the cytotoxicity of $CD2^+CD8^+$ NK cells differentiated by cytokines from c-$kit^+$ BM cells against K562 target cells for 28 days. Cytokines-induced NK cells as effector cells were incubated with K562 cells as target in a ratio of 100 : 1 for 4 h once a week. In results, $CD2^+CD8^+$ NK cells induced by cytokines and stromal cells showed a significantly increased cytotoxicity 21 days later. Whereas, our results indicated that c-$kit^+$ BM cells not pretreated with cytokines have lower levels of cytotoxicity. Taken together, this study suggests that cytokines-induced NK cells from porcine c-$kit^+$ BM cells may be used as adoptive transfer therapy if the known obstacles to xenografting (e.g. immune and non-immune problems) were overcome in the future.

Studies on the Glucose Isomerizing Enzyme -Part III The Effects of Metal Ions on the Reaction of K-17 Strain's Glucose Isomerizing Enzyme- (포도당(葡萄糖) 이성화(異性化) 효소(效素)에 관(關)한 연구(硏究) -제3보(第三報) 분리(分離) 선정(選定)된 균주(菌株) 효소(酵素)의 작용(作用)에 미치는 금속염(金屬鹽)의 영향(影響)에 대(對)해서-)

  • Seu, J.H.;Kim, C.K.;Ki, W.K.;Rhee, I.K.;Kwon, T.J.;Woo, D.L.
    • Applied Biological Chemistry
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    • v.11
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    • pp.55-61
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    • 1969
  • This K-17 strain was not absolutely requiring xylose as an inducer for enzyme formations. The most activity of this enzyme was lost when treated at $75^{\circ}C$. for 30 hours but was not influenced at $70^{\circ}C$. for 70 hours of treatment. The activity of this enzyme was increased by the addition of magnesium ions or cobalt ions in the reaction system. In the studies, we found that the magnesium ions simply activate the enzyme reaction and the cobalt ions do not but protect the enzyme from heat inactvation. And it was also found the phosphate buffer solution was very suitable as glucose dissolving solvent on the enzyme reaction. The mixed carbon source medium containing glucose, fructose, sorbitol, xylose and sucrose was more favorable for enzyme production then a sole carbon source containing medium on the shaking culture method.

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Studies on The Reduced Pressure Storage of Fruits (II) -Preservation of Jonathan under Various Pressures of Storage Chamber- (과실의 감압저장법에 관한 연구 ( II ) -감압도에 따른 저장성 비교(홍옥)-)

  • Kim, K.S.;Lee, K.L.;Hong, S.Y.;Sohn, T.H.
    • Applied Biological Chemistry
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    • v.11
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    • pp.77-82
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    • 1969
  • In order to determine an optimum pressure condition of the storage chamber of apples, several reduced pressure were examined for the Jonathan. The results obtained checking various storage conditions are as follows. 1. The optimum pressure of chamber atmosphere for apple storage was 10 cmHg. 2. Under the pressure of 10 cmHg, the normal (room) temperature storage was better than the cold storage. 3. Under reduced pressure, poly-ethylene film wrapping of apple showed a good result in a short-term (less than one and half month) experiment. 4. No noticeable effect was observed by O.E.D (Oxy-ethylene doxanole) or sodium dehydro acetate treatment. 5. Change of the components (total sugar, reduced sugar, acid and vitamin C) of apples according to the storage methods showed similar results to our previous report, Studies on The Reduced Pressure Storage of Fruits (I)

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Characterization of Oil-Degradation Biosurfactant Produced by Bacillus sp. TBM40-3 (Bacillus sp. TBM40-3에 의해 생성된 Biosurfactant의 유류분해 특성)

  • Kim, Sun-Hee;Lee, Sang-Cheol;Yoo, Ju-Soon;Joo, Woo-Hong;Chung, Soo-Yeol;Choi, Yong-Lark
    • Applied Biological Chemistry
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    • v.47 no.2
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    • pp.170-175
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    • 2004
  • In this paper we studied about Bacillus sp. TBM40-3 producing biosurfactants. The strains were isolated from Taeback Mountain soil and identified as Bacillus sp. by l6S rDNA nucleotides sequence analysis. The TBM40-3 was gram-positive and rod-shaped as observed by field emission scanning microscopy. After the cultivation TBM40-3 in LB broth for 90 h and the surface tension of supernatant was decreased to 29 mN/m. Emulsification activity and stability of crude biosurfactant was measured by using water-immiscible hydrocarbons and oil as substrate. Maximum emulsification activity and stability was obtained from soybean oil. Also, we confirmed that the TBM40-3 producing biosurfactant had an effect on crude oil while showing a superior effect as compared to chemically synthesized surfactants (SDS, Span85, Tween40, Triton X-100). As a result, the Bacillus sp. TBM40-3 producing biosurfactant had potent properties as an emulsifying agent and an emulsion stabilizing agent.

On Promoting the Coastal Transport of Container (컨테이너 연안해송 활성화에 관한 연구 -부산항을 중심으로-)

  • Roh H.S.;Lee C.Y.
    • Journal of Korean Port Research
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    • v.7 no.1
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    • pp.43-58
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    • 1993
  • There has been fast progress in economy in Korea derived by a consecutive five-year plan program for economic development started in the early 1960's. In the field of transportation, rapid changes in the technological environment of transportation and communication have brought a revolution of the transport system, of which inter-modal transportation through containerisation is typical. Because of the rapidly growing traffic volumes of cargo, especially container traffic, and lack of investment into transport infrastructure in the past, both road and railway are beyond their capacity. As a result, the public-road network has suffered a serious congestion problem. For instance, in relation to the corridor between Seoul and Pusan, today, it takes about 14 hours for the journey of container trailer through Kyongbu Expressway, for which it used to take only 7 hours in 1986. For the railway, though the congestion problem is not very serious compared with the road sector, a shortage of capacity on certain main lines has emerged as a problem as railway traffic has increased. Furthermore, the further expansion of the system in near future is difficult due to burden of higher construction the cost. Unlike these two modes, coastal shipping, which has been paid relatively less attention for commodity transport in Korea, shows no constraint in this respect. In addition, it is the most cost efficient mode of transport. This work therefore aims to make a proposal for the alternative inland transportation mode, which is to promote the coastal transport of container. Three obstructing factors for the promotion of the coastal transport are investigated and some solutions for those are suggested as follows : First, it appears to be essential to provide exclusive ports for the coastal shipping, that comply with simplification, specialization and rationalization. The optimum size of berths on the exclusive ports in Pusan port is estimated as 16-20. We found that it needs periodical study and publicity on the advantages from the adoption of the coastal mode. Inducing competition in the coastal shipping market is also necessary. For the supply of the fleet in the coastal shipping, chartering of the surplus ships in the oversea shipping is found to be more desirable than new shipbuilding. Second, to solve the fragmentation of the companies which wish to participate in the coastal transport, government has to implement the subsidy policy. The encouragement of participation of the shipping lines engaging in Korea-Japan run and Korea-East South Asia run, into coastal shipping also needs to be considered cautiously. Third, simplification of the document for entry in ports is needed for rational coastal shipping management. We can use B/L (Bill of Lading) for coastal shipping as a prerequisite to get the indemnity by P & I Club. The reduction of the government controls on entering and leaving the ports also needs.

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Moved of Applied Fertilizers through Volcanic Ash Soils in a Lysimeter Experiment (Lysimeter를 이용한 시비비료의 화산회토 토양중 이동에 관한 연구)

  • 강봉균;조남기
    • Journal of Soil and Groundwater Environment
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    • v.6 no.3
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    • pp.3-12
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    • 2001
  • This study conducted to Investigate the movement of fertilized nutrients in a volcanic ash soil in Jeju using by the pressure-vacuum soil water sampler. The percolated water to measure the ion concentration of leachates was taken from a lysimeter at depths of 20, 40, 60, 80, 100 and 120 cm in the soil in where a corn and potato were cultivated as a preceding and succeeding crop, respectively. Fertilizers of N-$P_2$O$_{5}$-$K_2$O were applied at the rate of 36-30-30 kg $10a^{-1}$ for the corn and 28-22-24 kg $10a^{-1}$ for the potato prior to planting of both crops. The highest concentrations of Cl , $NO_3$-N, $Ca^{+2}$ and $K^+$ in percolates were showed at 20cm and 40cm in soil depth at one month after fertilizing, and then gradually moved and reduced into below soil depths. At 5.5 months after fertilization, the concentrations in all soil depths were similar with the value of before fertilization. At depth of 120cm, the concentration of NO$_3$-N and the other cations in leachate was highest 1 to 1.5 months after fertilization. pH in percolated water was negatively correlated with NO$_3$-N concentration while the concentration of $NO_3$-N showed positive correlation between Cl, $Ca^{+2}$ and $Mg^{+2}$ concentrations. This result indicated that those cations can be leached out by accompanied with $NO_3$-N.

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