• BMB Reports
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• v.40 no.3
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• pp.448-452
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• 2007

We examined the contribution of CYP2C9 and CYP2C19 genotypes and drug interactions to the phenytoin metabolism among 97 Korean epileptic patients to determine if pharmacogenetic testing could be utilized in routine clinical practice. The CYP2C9 polymorphism is a wellknown major genetic factor responsible for phenytoin metabolism. The CYP219 polymorphism, with a high incidence of variant alleles, has a minor influence on phenytoin treated Koran patients. Using a multiple regression model for evaluation of the CYP2C9 and CYP2C19 genotypes, together with other non-genetic variables, we explained 39.6% of the variance in serum phenytoin levels. Incorporation of genotyping for CYP2C9 and CYP2C19 into a clinical practice may be of some help in the determination of phenytoin dosage. However, because concurrent drug treatment is common in patients taking phenytoin and many environmental factors are likely to play a role in drug metabolism, these factors may overwhelm the relevance of CYP polymorphisms in the clinical setting. Further investigations with an approach to dose assessment that includes comprehensive interpretation of both pharmacogenetic and pharmacokinetic data along with understanding of the mechanism of drug interactions in dosage adjustment is warranted.

• Journal of Ginseng Research
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• v.31 no.1
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• pp.1-13
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• 2007

We found that the main bacterial metabolite M1 is an active component of orally administered protopanxadiol-type ginsenosides, and that the anti-metastatic effect by oral administration of ginsenosides may be primarily mediated through the inhibition of tumor invasion, migration and growth of tumor cells by their metabolite M1. Pharmacokinetic study after oral administration of ginsenoside Rb1 revealed that M1 was detected in serum for 24 h by HPLC analysis but Rb1 was not detected. M1, with anti-metastatic property, inhibited the proliferation of murine and human tumor cells in a time- and concentration-dependent manner in vitro, and also induced apoptotic cell death (the ladder fragmentation of the extracted DNA). The induction of apoptosis by M1 involved the up-regulation of the cyclin-dependent kinase(CDK) inhibitor $p27^{Kip1}$ as well as the down-regulation of a proto-oncogene product c-Myc and cyclin D1 in a time-dependent manner. Thus, M1 might cause the cell-cycle arrest (G1 phase arrest) in honor cells through the up/down-regulation of these cell-growth related molecules, and consequently induce apoptosis. The nucleosomal distribution of fluorescence-labeled M1 suggests that the modification of these molecules is induced by transcriptional regulation. Tumor-induced angiogenesis (neovascularization) is one of the most important events concerning tumor growth and metastasis. Neovascularization toward and into tumor is a crucial step for the delivery of nutrition and oxygen to tumors, and also functions as the metastatic pathway to distant organs. M1 inhibited the tube-like formation of hepatic sinusoidal endothelial (HSE) cells induced by the conditioned medium of colon 26-L5 cells in a concentration-dependent manner. However, M1 at the concentrations used in this study did not affect the growth of HSE cells in vitro.

• Toxicological Research
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• v.22 no.1
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• pp.55-59
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• 2006

The purpose of this study was to investigate the toxicity of hematoporphyrin-coated magnetic ferrofluid (HP-MF) through intravenous administration in Sprague-Dawley rats. Each group was treated with either saline, or the HP-MF at 0.5, 1, 1.5, 2 and 4 ml/kg body weight (b.w.) for the observation of survival rate, clinical symptoms, laboratory values and histopathological findings. In this study, HP-MF was evaluated for the survival rates, symptoms, laboratory values and histopathological examination after treatments. The result revealed that the animals in the group of HP-MF at 2 and 4 ml/kg b.w. showed some lethality. In serum biochemistry, the levels of AST, ALT and ALP were increased in the MF and HP-MF treated groups. However, histopathological examination for the suspected organs showed no evidence of hepatotoxicity and nephrotoxicity of typical iron poisoning. Though the toxicity of HP-MF was higher than that of HP, long retention of hematoporphyrin via HP-MF provides additional benefit over conventional hematoporphyrin. HP-MF could be utilized as a potential photodynamic agent in cancer therapy. It is suggested to develop an efficient external magnetic device to attract hematoporphyrin in the target site, thereby enabling to administering a small amount of HP-MF.

• Biomolecules & Therapeutics
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• v.12 no.1
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• pp.49-54
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• 2004

The present study was conducted to investigate the potential subacute toxicity of CKD-602 by a 5-day repeated intravenous administration in Sprague-Dawley rats. CKD-602 was administered intravenously to male rats at dose levels of 0, 0.08, 0.2, and 0.5 mg/kg for 5 days. Studies included general observation, body weight changes, ophthalmoscopic examination, hematology, se겨m biochemistry, gross findings at necropsy and organ weight measurement. There were no deaths in any treatment group and treatment related clinical sign was depilation in the 0.5 mg/kg groups. The decrease or suppression of body weight was also observed dose-dependently in all treatment groups. Decreased leukocyte in all treatment groups, decreased platelet in the above 0.2 mg/kg groups and increase in the serum levels of total cholesterol in the 0.5 mg/kg group were considered as a treatment related toxic effects. Decreased weight of thymus in all treatment groups anti decreased weight of spleen in the above 0.2 mg/kg group were observed. The intravenous administration of CKD-602 caused depilation and decreased weight and had toxic effect on the leukocyte, platelet, spleen and thymus. In the condition of this study, the target organs were spleen and thymus and the toxic effect level was determined to be 0.2 mg/kg, but no-observed-adverse-effect level (NOAEL) was considered to be lower than 0.08 mg/kg.

• BMB Reports
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• v.34 no.5
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• pp.434-439
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• 2001

The effects of regular endurance exercise, or acute-exercise and rest on the levels of lipids, carnitines and carnitine palmitoyltransferase-I (CPT-I) were investigated in male Sprague-Dawley rats. The rats were exercise trained on a treadmill for 60 min per day for 60 days (long-term trained, LT), or non-trained for 59 days (NT) and exercised for 60 min on the 60th day. In NT rats, the levels of serum nonesterified carnitine (NEC), acidsoluble acylcarnitine (ASAC), and total carnitine (TONE) increased significantly during the post-exercise recovery period (PERP). In LT rats, ASAC, and TCNE, which increased right after the 60 min running session decreased to the levels of pre-exercise during the PERP. The levels of skeletal muscle ASAC in NT rats, which increased significantly by the acute-exercise, decreased to the pre-exercise levels during the PERP. However, the ASAC level in LT rats reached its peak at 4 h after running for 60 min. Liver triglyceride (TG) and total lipids (TL), which increased by the acute-exercise, decreased to the pre-exercise levels during the PERP in both NT and LT rats. CPT-I activity in NT rats increased significantly after 1 h of a 60-min exercise and slowly decreased to pre-exercise levels during the PERP. However, the CPT-I activity in LT rats, which increased significantly by the 60 min exercise, decreased slowly and reached its pre-exercise level within 8 h of the PERP. Northern blot analysis showed that the changes of CPT-I activities during the PERP coincided with changes in CPT-I mRNA levels. This study shows that both regular endurance exercise, and acute-exercise and rest, can influence differently the levels of carnitines, lipids and CPT-I in rats. The results suggest that regular endurance exercise, rather than the acute-exercise, can change effectively the distributions of carnitines, lipids and CPT-I in rats during exercise and rest.

• BMB Reports
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• v.34 no.6
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• pp.509-516
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• 2001

A genomic DNA fragment that contains the gene, which codes for a novel extracellular serine protease in Burkholderia pseudomallei, was cloned by using pQE40 as a vector. It was maintained in Escherichia coli JM109. The expression of the gene(s) resulted in the production of a 52 kDa protease. The recombinant protease was purified from the culture filtrate via ammonium sulfate fractionation, gel filtration, and anion-exchange chromatography. The purified protease had an optimum pH and temperature of pH 8.9 and $38^{\circ}C$, respectively. The protease activity was inhibited by EGTA, EDTA, and PMSF, but not 1,10-phenanthroline. The first 11 amino acid residues from the N-terminus of the purified protease were identified as LAPNDPYYYGY. PNDPYY was found to show homology to the Bacillus cereus microbial serine protease and B. subtilis PD498 serine protease. These results indicate that the protease that was purified in this study is an extracellular calcium-dependent serine protease. The purified protease was able to digest the human serum 19A, IgG, albumin, and transferrin, as well as bovine muscle actin and myosin. Furthermore, it was able to promote or cause dermonecrosis in experimental rabbits. These results propose the possible role of a novel B. pseudomallei extracellular calcium-dependent serine protease in the virulence of the pathogen.

• BMB Reports
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• v.41 no.2
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• pp.153-157
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• 2008

The objective of the present study was to identify mitochondrial components associated with the damage caused by iron to the rat heart. Decreased cell viability was assessed by increased presence of lactate dehydrogenase (LDH) in serum. To assess the functional integrity of mitochondria, Reactive Oxygen Species (ROS), the Respiratory Control Ratio (RCR), ATP and chelatable iron content were measured in the heart. Chelatable iron increased 15-fold in the mitochondria and ROS increased by 59%. Deterioration of mitochondrial function in the presence of iron was demonstrated by low RCR (46% decrease) and low ATP content (96% decrease). Using two dimensional gel electrophoresis (2DE), we identified alterations in 21 mitochondrial proteins triggered by iron overload. Significantly, expression of the $\alpha$, $\beta$, and d subunits of $F_1F_o$ ATP synthase increased along with the loss of ATP. This suggests that the $F_1F_o$ ATP synthase participates in iron metabolism.

• The Korea Journal of Herbology
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• v.23 no.4
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• pp.1-7
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• 2008

Objectives: Ephedrae herba, also known as Ma-huang, is a traditional Korean medicinal herb. It has been used to treat asthma, nose and lung congestion, and fever with anhidrosis for centuries. Recently, Ma-huang was used as a source of ephedrine in many dietary supplements for weight reduction in the United States. The objective of this study was to investigate the subacute toxicity of ephedrae herba extract in rats. Methods: SPF Sprague-Dawley male rats were administered orally with ephedrae herba extract for 4 weeks as several doses(0, 125, 250, 500, 1,000, and 2,000 mg/kg). We examined number of deaths, clinical signs, body weights and gross findings for experimental period. Results: No dead animals were found during the experimental period. In addition, no differences were found between control and treated groups in clinical signs, hematology, serum biochemistry, and other findings. Conclusions: In conclusion, above data suggest that no observed adverse effect level of ephedrae herba extract in SD rats might be over 2,000 mg/kg/day in this study.

• The Journal of the Korea Contents Association
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• v.15 no.6
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• pp.529-538
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• 2015

This study was carried out to evaluate the acute oral toxicity of Corydalis turtschaninovii BESS. in Sprague-Dawley(SD) rats. Male and female rats were administered orally with Corydalis turtschaninovii BESS water extract. We measured the number of death by clinical signs and gross findings for 7 days. After 7 days, we measured the whole body and individual organs' weight. We also analyzed hematological changes. The result, no dead SD rats and no clinical signs were found during the experiment period. Also other specific changes were not found between control and treated groups in hematology and serum biochemistry. The results indicated that there were no significant changes of gross body and individual organs weight in SD rats. These results suggest that water soluble extract of Corydalis turtschaninovii BESS. has not acute oral toxicity in SD rats.

• Journal of Microbiology and Biotechnology
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• v.19 no.1
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• pp.83-92
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• 2009

Individual immunochromatographic assays (ICG) for ochratoxin A (OTA) and zearalenone (ZEA) were optimized and used in the development of a one-step simultaneous immunochromatographic assay (OS-ICG) for the rapid multianalysis of two mycotoxins in corn samples. The nitrocellulose membrane of the OS-ICG was treated with OTA-bovine serum albumin (BSA), ZEA-ovalbumin (OVA), and anti-mouse IgG in the OTA test, ZEA test, and control zones, respectively. Monoclonal antibody-gold conjugates (OTA3 MAb-gold and ZEA2C5 MAb-gold) were sprayed onto the conjugate pad. The visual detection limits were 2.5 and 5 ng/ml for OTA and ZEA, respectively, and the results were obtained within 15 min after starting the analysis. An efficient, simple, and rapid extraction method using 30% MeOH/PBS was established and validated by analyzing the corn samples spiked with OTA/ZEA mixtures (0/0, 5/10, 10/20, and $20/30\;{\mu}g/kg$). The cut-off values of the OS-ICG for the spiked corn were 5 and $10\;{\mu}g/kg$ for OTA and ZEA, respectively. Natural corn samples were analyzed by OS-ICG, direct competitive enzyme-linked immunosorbent assay (DC-ELISA), and HPLC. Results of the OS-ICG were in good agreement with those obtained by DC-ELISA and HPLC. The developed OS-ICG offers a rapid, easy-to-use, and portable analytical system and can be used as a convenient qualitative tool for the on-site simultaneous determination of OTA and ZEA in cereals, food, and agricultural products in one analytical cycle.