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Bioequivalence of Loxipen Tablet to Loxonin Tablet (Sodium Loxoprofen Anhydride 60 mg) (록소닌 정(록소프로펜 나트륨 무수물 60 mg)에 대한 록시펜 정의 생물학적 동등성)

  • Kim, In-Wha;Han, Tae-Gyu;Kim, Kyung-Sik;Chung, Suk-Jae;Lee, Min-Hwa;Shim, Chang-Koo
    • Journal of Pharmaceutical Investigation
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    • v.28 no.3
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    • pp.185-191
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    • 1998
  • A bioequivalence study of the Loxipen tablets (Dae Wha Pharmaceutical Co., Korea) to the Loxonin tablets (Dong Hwa Pharmaceutical Co., Korea), formulations of sodium loxoprofen anhydrous 60 mg, was conducted. Sixteen healthy Korean male subjects received each formulation at the dose of 60 mg as sodium loxoprofen anhydrous in a $2{\times}2$ crossover study. There was a 2-week washout period between the dose. Plasma concentrations of loxoprofen were monitored by an HPLC method for over a period of 6 h after each administration. AUC (area under the plasma concentration-time curve from time zero to infinity) was calculated by the linear trapezoidal and extrapolation method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ $(time\;to\;reach\;C_{max})$ were compiled from the plasma drug concentration-time data. Analysis of variance (ANOVA) revealed that there are no differences in AUC, $C_{max}$ and $T_{max}$ between the formulations. The apparent differences between the formulations in these parameters were all far less than 20% (i.e., 5.88, 7.81 and 6.09% for AUC, $C_{max}$ and $T_{max}$, respectively). Minimum detectable differences (%) at ${\alpha}=0.1$ and $1-{\beta}=0.8$ were all less than 20% difference in these parameters between the formulations were all over 0.8 (i.e., 15.81, 13.13 and 19.85 for AUC, $C_{max}$ and $T_{max}$, respectively). The 90% confidence intervals for these parameters were also within ${\pm}20%$ (i.e., $-16.52{\sim}4.77$, $-16.65{\sim}1,02$ and $-19.45{\sim}7.28%$ for AUC, $C_{max}$ and $T_{max}$, respectively). These results satisfy the bioequivalence criteria of the Korea Food and Drug Administration (KFDA) guidelines (No. 98-51). Therefore, these results indicate that the 2 formulations of loxoprofen are bioequivalent and, thus, may be prescribed interchangeably.

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Expression and Characterization of Calcium- and Zinc-Tolerant Xylose Isomerase from Anoxybacillus kamchatkensis G10

  • Park, Yeong-Jun;Jung, Byung Kwon;Hong, Sung-Jun;Park, Gun-Seok;Ibal, Jerald Conrad;Pham, Huy Quang;Shin, Jae-Ho
    • Journal of Microbiology and Biotechnology
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    • v.28 no.4
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    • pp.606-612
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    • 2018
  • The enzyme xylose isomerase (E.C. 5.3.1.5, XI) is responsible for the conversion of an aldose to ketose, especially xylose to xylulose. Owing to the ability of XI to isomerize glucose to fructose, this enzyme is used in the food industry to prepare high-fructose corn syrup. Therefore, we studied the characteristics of XI from Anoxybacillus kamchatkensis G10, a thermophilic bacterium. First, the gene coding for XI (xylA) was inserted into the pET-21a(+) expression vector and the construct was transformed into the Escherichia coli competent cell BL21 (DE3). The expression of recombinant XI was induced in the absence of isopropyl-thio-${\beta}$-galactopyranoside and purified using Ni-NTA affinity chromatography. The optimum temperature of recombinant XI was $80^{\circ}C$ and measurement of the heat stability indicated that 55% of residual activity was maintained after 2 h incubation at $60^{\circ}C$. The optimum pH was found to be 7.5 in sodium phosphate buffer. Magnesium, manganese, and cobalt ions were found to increase the enzyme activity; manganese was the most effective. Additionally, recombinant XI was resistant to the presence of $Ca^{2+}$ and $Zn^{2+}$ ions. The kinetic properties, $K_m$ and $V_{max}$, were calculated as 81.44 mM and $2.237{\mu}mol/min/mg$, respectively. Through redundancy analysis, XI of A. kamchatkensis G10 was classified into a family containing type II XIs produced by the genera Geobacillus, Bacillus, and Thermotoga. These results suggested that the thermostable nature of XI of A. kamchatkensis G10 may be advantageous in industrial applications and food processing.

Long-term Activation of c-Jun N-terminal Kinase through Receptor Interacting Protein is Associated with DNA Damage-induced Cell Death

  • Seok, Jeong-Ho;Park, Kyeong-Ah;Byun, Hee-Sun;Won, Min-Ho;Shin, Sang-Hee;Choi, Byung-Lyul;Lee, Hyun-Ji;Kim, Young-Rae;Hong, Jang-Hee;Park, Jong-Sun;Hur, Gang-Min
    • The Korean Journal of Physiology and Pharmacology
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    • v.12 no.4
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    • pp.185-191
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    • 2008
  • Activation of c-Jun N-terminal kinase (JNK), a member of the mitogen-activated protein kinase family, is an important cellular response that modulates the outcome of the cells which are exposed to the tumor necrosis factor (TNF) or the genotoxic stress including DNA damaging agents. Although it is known that JNK is activated in response to genotoxic stress, neither the pathways to transduce signals to activate JNK nor the primary sensors of the cells that trigger the stress response have been identified. Here, we report that the receptor interacting protein (RIP), a key adaptor protein of TNF signaling, was required to activate JNK in the cells treated with certain DNA damaging agents such as adriamycin (Adr) and 1-${\beta}$-D-arabinofuranosylcytosine (Ara-C) that cause slow and sustained activation, but it was not required when treated with N-methyl-N-nitro-N-nitrosoguanidine (MNNG) and short wavelength UV, which causes quick and transient activation. Our findings revealed that this sustained JNK activation was not mediated by the TNF (tumor necrosis factor) receptor signaling, but it required a functional ATM (ataxia telangiectasia) activity. In addition, JNK inhibitor SP-600125 significantly blocked the Adr-induced cell death, but it did not affect the cell death induced by MNNG. These findings suggest that the sustained activation of JNK mediated by RIP plays an important role in the DNA damage-induced cell death, and that the duration of JNK activation relays a different stress response to determine the cell fate.

Median Control Chart for Nonnormally Distributed Processes (비정규분포공정에서 매디안특수관리도의 모형설계와 적용연구)

  • 신용백
    • Journal of the Korean Professional Engineers Association
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    • v.20 no.3
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    • pp.15-25
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    • 1987
  • Statistical control charts are useful tools to monitor and control the manufacturing processes and are widely used in most Korean industries. Many Korean companies, however, do not always obtain desired results from the traditional control charts by Shewhart such as the X-chart, X-chart, X-chart, etc. This is partly because the quality charterstics of the process are not distributed normally but are skewed due to the intermittent production, small lot size, etc. In Shewhart X-chart, which is the most widely used one in Korea, such skewed distributions make the plots to be inclined below or above the central line or outside the control limits although no assignable causes can be found. To overcome such shortcomings in nonnormally distributed processes, a distribution-free type of confidence interval can be used, which should be based on order statistics. This thesis is concerned with the design of control chart based on a sample median which is easy to use in practical situation and therefore properties for nonnormal distributions may be easily analyzed. Control limits and central lines are given for tile more famous nonnormal distributions, such as Gamma, Beta, Lognormal, Weibull, Pareto, Truncated-normal distributions. Robustness of the proposed median control chart is compared with that of the X-chart, the former tends to be superior to the latter as the probability distribution of the process becomes more skewed. The average run length to detect the assignable cause is also compared when the process has a Normal or a Gamma distribution for which the properties of X are easy to verify, the proposed chart is slightly worse than the X-chart for the normally distributed product but much better for Gamma-distributed products. Average Run Lengths of the other distributions are also computed. To use the proposed control chart, the probability distribution of the process should be known or estimated. If it is not possible, the results of comparison of the robustness force us to use the proposed median control chart based on a normal distribution. To estimate the distribution of the process, Sturge's formula is used to graph the histogram and the method of probability plotting, $X^2$-goodness of fit test and Kolmogorov-Smirnov test, are discussed with real case examples. A comparison of the propose4 median chart and the X chart was also performed with these examples and the median chart turned out to be superior to the X-chart.

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Suppressive effects of $Schizandra$ $chinensis$ Baillon water extract on allergy-related cytokine generation and degranulation in IgE-antigen complex-stimulated RBL-2H3 cells

  • Chung, Mi-Ja;Kim, Jeong-Mi;Lee, Sang-Chul;Kim, Tae-Woo;Kim, Dae-Jung;Baek, Jong-Mi;Kim, Tae-Hyuk;Lee, Jae-Sung;Kim, Kyoung-Kon;Yoon, Jin-A;Choe, Myeon
    • Nutrition Research and Practice
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    • v.6 no.2
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    • pp.97-105
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    • 2012
  • $Schizandra$ $chinensis$ Baillon is a traditional folk medicine plant that is used to treat and prevent several inflammatory diseases and cancer in Korea, but the underlying mechanisms involved in its anti-allergic activity are not fully understood. This study was designed to investigate mechanisms of anti-allergic activity of a $Schizandra$ $chinensis$ Baillon water extract (SCWE) in immunoglobulin E (IgE)-antigen complex-stimulated RBL2H3 cells and to assess whether gastric and intestinal digestion affects the anti-allergic properties of SCWE. Oxidative stress is an important consequence of the allergic inflammatory response. The antioxidant activities of SCWE increased in a concentration-dependent manner. RBL-2H3 cells were sensitized with monoclonal anti-dinitrophenol (DNP) specific IgE, treated with SCWE, and challenged with the antigen DNP-human serum albumin. SCWE inhibited ${\beta}$-hexosaminidase release and expression of interleukin (IL)-4, IL-13, and tumor necrosis factor-alpha (TNF-${\alpha}$) mRNA and protein in IgE-antigen complex-stimulated RBL2H3 cells. We found that digested SCWE fully maintained its antioxidant activity and anti-allergic activity against the IgE-antigen complex-induced activation of RBL-2H3 cells. SCWE may be useful for preventing allergic diseases, such as asthma. Thus, SCWE could be used as a natural functional ingredient for allergic diseases in the food and/or pharmaceutical industries.

Processing and Physicochemical Properties of Collagen from Yellowfin Tuna (Thunnus albacares) Abdominal Skin (황다랑어 복부 껍질을 이용한 콜라겐의 제조 및 물리화학적 특성 해석)

  • Yoo, Sung-Jae;Cho, Sueng-Mock;Woo, Jin-Wook;Kim, Sang-Ho;Han, Yoo-Na;Ahn, Ju-Ryun;Kim, Su-Yeon;Kim, Tae-Wan;Kim, Seon-Bong
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.41 no.6
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    • pp.427-434
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    • 2008
  • Processing of collagen from yellowfin tuna (Thunnus albacares) abdominal skins was optimized by response surface methodology and central composite design. The values of independent variables at optimal conditions were NaOH concentration: 0.5 N, NaOH treatment time: 36.2 hr, pepsin concentration: 1:4.9 ratio (0.245%, w/v), and digestion time: 48.1 hr, respectively. The collagen content estimated under optimal conditions was 33.1%, and the actual experimental collagen content was 32.3%. Physicochemical properties of collagen from yellowfin tuna abdominal skin were investigated by amino acids analysis, SDS-PAGE, FT-IR, viscosity and denaturation temperature. Amino acids content of the collagen was 21.0%. SDS-PAGE pattern of the collagen showed two different $\alpha$-chain (${\alpha}_1$- and ${\alpha}_2$- chain), $\beta$-component and $\gamma$-component. The spectrum of FT-IR of the collagen showed wavenumber at 3,434, 1,650, 1,542 and $1,235\;cm^{-1}$ representing the regions of amide A, I, II and III, respectively. Relative viscosity of the collagen decreased continuously on heating up to $32^{\circ}C$, and the rate of decrease was retarded in the temperature range of $35-50^{\circ}C$. Denaturation temperature (Td) of the collagen solution (0.06%, w/v) was $31^{\circ}C$ and was lower than calf skin collagen ($35^{\circ}C$).

Optimization of the Reaction Conditions for (R)-Phenyl-1,2-ethanediol Preparation by Recombinant Epoxide Hydrolase from Caulobacter crescentus (재조합 Caulobacter crescentus 에폭사이드 가수분해효소를 이용한 광학활성 Diol 제조 조건의 최적화)

  • Lee, Ok-Kyung;Kim, Hee-Sook
    • Microbiology and Biotechnology Letters
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    • v.35 no.4
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    • pp.285-291
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    • 2007
  • Enantioconvergent hydrolysis process for the preparation of chiral diol from racemic epoxides by using the recombinant Caulobacter crescentus epoxide hydrolase (CcEH) in Escherichia coli BL21 (DE3) was optimized. For the optimization, the effects of detergent, temperature and product inhibition on the enantiopurity and the yield of diol were investigated. (R)-phenyl-1,2-ethanediol with 92% enantiomeric excess and 56% yield from 20 mM racemic styrene oxide was obtained by using the recombinant CcEH at the optimal condition of $10^{\circ}C$ and the addition of 2% (w/v) Tween 80. At 50 mM racemic styrene oxide was used as a substrate, (R)-phenyl-1,2-ethanediol was obtained with 87% enantiomeric excess and 77% yield. Racemic phenyl-1,2-ethanediol, (R)-phenyl-1,2-ethanediol and (S)-phenyl-1,2-ethanediol dramatically inhibited the hydrolytic activity of the recombinant CcEH. These results suggested that another EH with the regioselectivity on ${\beta}$-position of (R)-enantiomer and without feedback inhibition by products would be needed as the partner EH of C. crescentus EH.

Acetone, Butanol, Ethanol Production from Undaria pinnatifida Using Clostridium sp. (Clostridium 종을 이용한 미역으로부터 아세톤, 부탄올, 에탄올 (ABE) 생산)

  • Kwon, Jeong Eun;Gwak, Seung Hee;Kim, Jin A;Ryu, Ji A;Park, Sang Eon;Baek, Yoon Seo;Heo, A Jeong;Kim, Sung-Koo
    • Microbiology and Biotechnology Letters
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    • v.45 no.3
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    • pp.236-242
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    • 2017
  • The conversion of marine biomass to renewable energy has been considered an alternative to fossil fuels. Butanol, in particular, can be used directly as a fuel. In this experiment, the brown alga Undaria pinnatifida was selected as a biomass for biobutanol production. Hyper thermal (HT) acid hydrolysis was used as an acid hydrolysis method to produce monosaccharides. The optimal pretreatment conditions for U. pinnatifida were determined as slurry with 10% (w/v) U. pinnatifida content and 270 mM $H_2SO_4$, and heating at $160^{\circ}C$ for 7.5 min. Enzymatic saccharification was carried out with Celluclast 1.5 L, Viscozyme L, and Ultraflo Max. The optimal saccharification condition was 12 U/ml Viscozyme L. Fermentations were carried out for the production of acetone, butanol, and ethanol by Clostridium acetobutylicum KCTC 1724, Clostridium beijerinckii KCTC 1785, and Clostridium tyrobutyricum KCTC 5387. The fermentations were carried out using a pH-control. The optimal ABE fermentation condition determined using C. acetobutylicum KCTC 1724 adapted to 160 g/l mannitol. An ABE concentration of 9.05 g/l (0.99 g/l acetone, 5.62 g/l butanol, 2.44 g/l ethanol) was obtained by the consumption of 24.14 g/l monosaccharide with $Y_{ABE}$ of 0.37 in pH 5.0.

GRIM-19 Expression and Function in Human Gliomas

  • Jin, Yong-Hao;Jung, Shin;Jin, Shu-Guang;Jung, Tae-Young;Moon, Kyung-Sub;Kim, In-Young
    • Journal of Korean Neurosurgical Society
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    • v.48 no.1
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    • pp.20-30
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    • 2010
  • Objective : We determined whether the expression of GRIM-19 is correlated with pathologic types and malignant grades in gliomas, and determined the function of GRIM-19 in human gliomas. Methods : Tumor tissues were isolated and frozen at $-80^{\circ}C$ just after surgery. The tissues consisted of normal brain tissue (4), astrocytomas (2), anaplastic astrocytomas (2), oligodendrogliomas (13), anaplastic oligodendrogliomas (11), and glioblastomas (16). To profile tumor-related genes, we applied RNA differential display using a $Genefishing^{TM}$ DEG kit, and validated the tumor-related genes by reverse transcription polymerase chain reaction (RT-PCR). A human glioblastoma cell line (U343MG-A) was used for the GRIM-19 functional studies. The morphologic and cytoskeletal changes were examined via light and confocal microscopy. The migratory and invasive abilities were investigated by the simple scratch technique and Matrigel assay. The antiproliferative activity was determined by thiazolyl blue Tetrazolium bromide (MTT) assay and FACS analysis. Results : Based on RT-PCR analysis, the expression of GRIM-19 was higher in astrocytic tumors than oligodendroglial tumors. The expression of GRIM-19 was higher in high-grade tumors than low-grade tumors or normal brain tissue; glioblastomas showed the highest expression. After transfection of GRIM-19 into U343MG-A, the morphology of the sense-transfection cells became larger and more spindly. The antisensetransfection cells became smaller and rounder compared with wild type U343MG-A. The MTT assay showed that the sense-transfection cells were more sensitive to the combination of interferon-$\beta$ and retinoic acid than U343MG-A cells or antisense-transfection cells; the antiproliferative activity was related to apoptosis. Conclusion : GRIM-19 may be one of the gene profiles which regulate cell death via apoptosis in human gliomas.

Characterization of Intermediate Conductance $K^+$ Channels in Submandibular Gland Acinar Cells

  • Cho, Sung-Man;Piao, Zheng-Gen;Kim, Yoon-Bae;Kim, Joong-Soo;Park, Kyung-Pyo
    • The Korean Journal of Physiology and Pharmacology
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    • v.6 no.6
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    • pp.305-309
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    • 2002
  • There are some evidences that $K^+$ efflux evoked by muscarinic stimulation is not mainly mediated by large conductance $K^+$ (BK) channels in salivary gland. In this experiment, we therefore characterised non BK channels in rat submandibular gland acinar cells and examined the possibility of agonist effect on this channel using a patch clamp technique. Two types of $K^+$ channels were observed in these cells. BK channels were observed in 3 cells from total 6 cells and its average conductance was $152{\pm}7$ pS (n=3). The conductance of the another types of $K^+$ channel was estimated as $71{\pm}7$ pS (n=6). On the basis of the conductance of this channel, we defined this channel as intermediate conductance $K^+$ (IK) channels, which were observed from all 6 cells we studied. When we increased $Ca^{2+}$ concentration of the bath solution in inside-out mode, the IK channel activity was greatly increased, suggesting this channel is $Ca^{2+}$ sensitive. We next examined the effect of carbachol (CCh) and isoproterenol on the activity of the IK channels. $10^{-5}$ M isoproterenol significantly increased the open probability (Po) from $0.08{\pm}0.02$ to $0.21{\pm}0.03$ (n=4, P<0.05). Application of $10^{-5}$ M CCh also increased Po from $0.048{\pm}0.03$ to $0.55{\pm}0.33$ (n=5, P<0.05) at the maximum channel activity. The degree of BK channel activation induced by the same concentration of CCh was lower than that of IK channels; Po value was $0.011{\pm}0.003$ and $0.027{\pm}0.005$ in control and during CCh stimulation (n=3), respectively. The result suggests that IK channels exist in salivary acinar cells and its channel activity is regulated by muscaricinic and ${\beta}-adrenergic$ agonist. We conclude that IK channels also play a putative role in secretion as well as the BK channels in rat submandibular gland acinar cells.