• Korean Journal of Clinical Pharmacy
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• v.3 no.1
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• pp.79-88
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• 1993

Bioequivalence(BE) test of commercially available sustained release tablets of diltiazem hydrochloride(DTZ) was performed to give some guidelines to BE test in korea in case of which drugs with low oral bioavaiiability(BA) due to substantial first-pass hepatic loss form pharmacologically active metabolites. In such cases, the pharmacologic activity after oral administration is greater than anticipated from BA data, based on chemical assay of drug alone. Therefore, this paper explores the use and meaning of area under the plasma concentration-time(AUC) data of parent and its metabolites to access BA if sustained release tablets. Normal healthy male volunteers(n=14) were randomly divided into 2 groups, and sustained release reference$(Herbesser^{(R)})$ and test$(Herben^{(R)})$ tablets of DTZ-30mg were given orally by balanced two-period cross-over dosing schedule. The plasma concentration of DTZ and and its active metabolite, desacetyldiitiazem(DAD), were determined by high performance liquid chromatography, and, $AUC_{DTZ},\;AUC_{DAD},\;AUC_{DTZ+DAD},\;C_{max}\;and\;T_{max}$ obtained. Analysis of varlance(ANOVA) showed that $AUC_{DTZ}\;and\;C_{max}$ passed the standard $(\alpha=0.05,\;1-\beta\geq0.8,\;\Delta\leq0.2)$ of BE test of korea, but $AUC_{DAD}$ was not satisfied from the standpoint of power. On the other hand, $AUC_{DTZ\midDAD}$ may be more avaliable than $AUC_{DAD}$ from the standpoint of statistics and pharmacologic equivalence.

• Journal of Pharmaceutical Investigation
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• v.26 no.4
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• pp.309-314
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• 1996

The purpose of this study is to explain the relationship between the pharmacological mechanism of levamisole and the cellular activity of cellular alkaline phosphatase (ALPase) in kidney cells. The results of our investigation were as follows. 1. Cellular ALPase activity in Macacus rhesus monkey kidney cells (MA 104 cells) and primary cultured rabbit kidney proximal tubular cells treated with levamisole was increased about two or three times than control. However, 50% of ALPase activity in cultured medium was inhibited by levamisole itself. 2. The proliferation of MA 104 and cultured rabbit kidney proximal tubular cells was linearly decreased in paralleled with increase of levamisole concentration $(50\;and\;500\;{mu}M)$ with MTT test. 3. In the heat stability tests, the inhibition of ALPase activity with and without levamisole at $56^{\circ}C$ in MA 104 cells showed different $IC_{50}$ values. 4. HPLC analysis of levamisole metabolites produced by cultured MA 104 cells suggested that the formation of a metabolite, that may be associated with its increase of cellular ALPase activity. Based on these results, we assumed that the increase of cellular ALPase activity by levamisole was evoked by modification of the ALPase catalytic sites.

• Microbiology and Biotechnology Letters
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• v.40 no.1
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• pp.10-16
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• 2012

The Streptomyces peucetius OIM (Overproducing Industrial Mutant) strain is a recursively-mutated and optimally-screened strain used for the industrial production of polyketide antibiotics, such as doxorubicin (DXR). Using the S. peucetius OIM mutant strain as a surrogate host, a model minimal polyketide pathway for aloesaponarin II, an actinorhodin shunt product, was cloned in a high-copy conjugative plasmid, followed by functional pathway expression and quantitative metabolite analysis. The level of aloesaponarin II production was noted as being significantly higher in the OIM strain than in the wild-type S. peucetius, as well as in the regulatory network-stimulated S. coelicolor mutant strain. Moreover, the aloesaponarin II production level was seen to be even higher in a down-regulator $wblA_{spe}$-deleted S. peucetius OIM strain, implying that the rationally-engineered S. peucetius OIM mutant strain could be used as an efficient surrogate host for the high expression of foreign polyketide pathways.

• Journal of Microbiology and Biotechnology
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• v.22 no.2
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• pp.256-263
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• 2012

A strain of bacterium producing antifungal antibiotic was isolated and identification of the strain was attempted. We could identify the bacterium as being a Bacillus sp., based on morphological observation, physiological characteristics, and 16S rDNA sequence analysis, thus leading us to designate the strain as Bacillus sp. AH-E-1. The strain showed potent antibiotic activity against phytopathogenic and human pathogenic fungi by inducing mycelial distortion and swelling and inhibiting spore germination. The antibiotic metabolite produced by the strain demonstrated excellent thermal and pH (2-11) stability, but was labile to autoclaving. From these results, we could find a broader antifungal activity of Bacillus genus. Isolation and characterization of the active agent produced by the strain are under progress.

• Toxicological Research
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• v.28 no.4
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• pp.269-277
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• 2012

The purpose of this study was to understand the mechanism of cardiovascular disease (CVD) caused by exposure to hazardous chemicals. We investigated changes in the symptoms of metabolic syndrome, which is strongly related to CVD, and in levels of other CVD risk factors, with a special emphasis on the roles of catecholamines and oxidative stress. The results revealed that neither body mass index (BMI) nor waist and hip circumferences were associated with exposure to hazardous chemicals. Among metabolic syndrome criteria, only HDL-cholesterol level increased on exposure to hazardous chemicals. Levels of epinephrine (EP) and norepinephrine (NEP) were not influenced by exposure to hazardous chemicals; however, the total antioxidative capacity (TAC) reduced because of increased oxidative stress. Both hazardous chemical exposure level and metabolite excretion were related to EP, NEP, and the oxidative stress index (OSI). Logistic regression analysis with these factors as independent variables and metabolic syndrome criteria as dependent variables revealed that EP was associated with blood pressure, and NEP with metabolic syndrome in the chemical-exposed group. In conclusion, the results suggest that reactive oxygen species generated and oxidative stress due to exposure to hazardous chemicals act as mediators and cause changes in the physiological levels of EP and NEP to increase blood pressure. This ultimately leads to the development of CVD through increase in cholesterol, triglyceride, and blood glucose levels by lipid peroxidation.

• Journal of Food Hygiene and Safety
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• v.32 no.6
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• pp.531-535
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• 2017

In this study, Leuconostoc mesenteroides CJNU0041 was isolated from Korean traditional food kimchi and antimicrobial activity of fermented broccoli with the isolate was tested against pathogenic Clostridium difficile. L. mesenteroides CJNU0041 showed higher glucosidase activity than other isolates. As the results of physiological properties such as pH and viable cell count during broccoli fermentation with L. mesenteroides CJNU0041, we confirmed that 48 hours was optimal fermentation time. As the results of metabolite analysis by HPLC, metabolites were changed during the fermentation. Especially, the growth of C. difficile was inhibited by the fermented broccoli. Therefore, L. mesenteroides CJNU0041 might be a candidate for improving the functionality of natural materials by lactic acid fermentation.

• Journal of the Korean Magnetic Resonance Society
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• v.16 no.2
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• pp.91-102
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• 2012

Metabolomics is the systematic identification and quantification of all metabolites in an organism or biological sample. NMR has been used as a major application tool in plant metabolomics such as quality control, chemotaxonomy, and analysis of genetically modified plants. Herbal medicines are the important therapeutics and are used to manage common diseases such as cold, inflammation, pain, heart diseases, liver cirrhosis, diabetes and central nerve system diseases. Herb plants include various kinds of species such as geranium, mint, and thyme and so on and contain different kinds of metabolites. We performed NMR-based metabolomics study on the seven different species of herb plants using $^1H$ NMR experiments and OPLS-DA to understand the correlation between the classification of herb plants and their metabolite contents. This study showed clear metabolic discrimination among various herb plants. This metabolmics study found several diagnostic NMR signals which are able to be used as bio-markers for identification of the specific herb plants among various species. Clear metabolic discrimination of herb plants suggests three chemotaxonomic groups of herb species.

• Analytical Science and Technology
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• v.32 no.5
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• pp.163-172
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• 2019

Methamphetamine (MA) is currently the most abused illicit drug in Korea and its major metabolite is amphetamine (AP). As MA exist as two enantiomers with the different pharmacological properties, it is necessary to determine their respective amounts in a sample. Thus a chiral stationary phase liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for identification and quantification of d-MA, l-MA, d-AP, and l-AP in human urine. Urine sample ($200{\mu}L$) was diluted with pure water and purified using solid-phase extraction (SPE) cartridge. A $5-{\mu}L$ aliquot of SPE treated sample solution was injected into LC-MS/MS system. Chiral separation was carried out on the Astec Chirobiotic V2 column with an isocratic elution for each enantiomer. Identification and quantification of enantiomeric MA and AP was performed using multiple reaction monitoring (MRM) detection mode. Linear regression with a $1/x^2$ as the weighting factor was applied to generate a calibration curve. The linear ranges were 25-1000 ng/mL for all compounds. The intra- and inter-day precisions were within 3.6 %, while the intra- and inter-day accuracies ranged from -5.4 % to 11.8 %. The limits of detection were 2.5 ng/mL (d-MA), 3.5 ng/mL (l-MA), 7.5 ng/mL (d-AP), and 7.5 ng/mL (l-AP). Method validation parameters such as selectivity, matrix effect, and stability were evaluated and met acceptance criteria. The applicability of the method was tested by the analysis of genuine forensic urine samples from drug abusers. d-MA is the most common compound found in urine and mainly used by abusers.

• Journal of Ginseng Research
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• v.45 no.6
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• pp.726-733
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• 2021

Background: Panax notoginseng is a highly valued medicinal herb used widely in China and many Asian countries. Its root and rhizome have long been used for the treatment of cardiovascular and hematological diseases. Imaging the spatial distributions and dynamics of metabolites in heterogeneous plant tissues is significant for characterizing the metabolic networks of Panax notoginseng, and this will also provide a highly informative approach to understand the complex molecular changes in the processing of Panax notoginseng. Methods: Here, a high-sensitive MALDI-MS imaging method was developed and adopted to visualize the spatial distributions and spatiotemporal changes of metabolites in different botanical parts of Panax notoginseng. Results: A wide spectrum of metabolites including notoginsenosides, ginsenosides, amino acids, dencichine, gluconic acid, and low-molecular-weight organic acids were imaged in Panax notoginseng rhizome and root tissues for the first time. Moreover, the spatiotemporal alterations of metabolites during the steaming of Panax notoginseng root were also characterized in this study. And, a series of metabolites such as dencichine, arginine and glutamine that changed with the steaming of Panax notoginseng were successfully screened out and imaged. Conclusion: These spatially-resolved metabolite data not only enhance our understanding of the Panax notoginseng metabolic networks, but also provide direct evidence that a serious of metabolic alterations occurred during the steaming of Panax notoginseng.

• Plant Breeding and Biotechnology
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• v.5 no.3
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• pp.192-203
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• 2017

Metabolite profile is a powerful analytical technique to identify the functional characterization of plants. In this study, the phytochemicals and secondary metabolites of lentils (Lens culinaris) were analyzed to compare the anti-oxidative activities according to the different colors. The polar metabolites, fatty acids, carotenoids, flavonoids, anthocyanins, total phenolic acids, DPPH activity were analyzed. Three kind of lentils, French green whole lentil (FG), red whole lentil (LR), and green whole lentil (LG) (ASIA SEED Co., LTD), were used for this study. Fatty acids, phytochemicals, and antioxidative components from each lentil varieties were analyzed by official methods. The contents of lutein in carotenoids were 6-9 times higher than zeaxanthin in all lentils, but were not significantly different among three varieties. The content of carotenoids in FG was lower significantly than those in the LR and LG. Myricetin and luteolin were detected in the only FG. Kaempferol and delphinidin were significantly highest in the FG. Most of the phenolic acids except coumarate were higher in FG and LG than in LR. Also antioxidant effects ($EC_{50}$) were higher in FG and LG than in LR. The analyzed metabolites obtained from lentils showed distinct separation in the PCA results according to the varieties. Also, lentils showed different anti-oxidant profiles according to the colors. FG and LG showing higher contents of phytochemicals showed higher antioxidative activity than LG containing relative low contents of phytochemicals.