• Journal of Society of Preventive Korean Medicine
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• v.19 no.3
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• pp.91-102
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• 2015

Objective : The purpose of this study is to find out the possibility of application to herbal medicine's report form for adverse drug reaction (ADR) by reviewing and analyzing Asian countries's ADR report forms. Method : We investigated, compared, and analyzed ADR report forms (ADR-RF) of Asian countries's ADR institutions (ACAI), such as, Korea institute of drug safety & risk management and Dongguk university Ilsan oriental hospital (DUIOH) in Korea, national center for ADR monintoring (NCAM) in China, pharmaceuticals and medical devices agency (PMDA) in Japan, Ministry of Health and Welfare (MOHW) in Taiwan, and drug office, department of health, the government of the Hong Kong special administrative region (GHKSAR) in Hong Kong. Results : ADR-RF for ACAI included common contents, such as, patients information (name(initial), gender, age, weight), adverse event (AE)'s report information (Recognition and report for AE occurrence, first or follow up report, Severe AE), the detailed information of AE (the title of AE, onset & closing date of AE symptoms, the progress & results detailed test of AE), the information of AE's medicine (the types of medicine, product name, ingredient name, suspected or combination drug, single dose & frequency, dosage form, administration route, dealing for AE-suspected medicine), and AE reporter's information (reporter's information, institution's information). Taiwan had ADR-RF and the department exclusively for herbal medicine (HM), but others (except DUIOH) had not only no ADR report form but also contents for HM. Conclusion : ADR-RF for HM have to include the common contents of ACAI at least, as well as HM information related to ADR, such as the title, composition and types of HM, history related to HM's ADR, and the contents of drug-induced liver injury and so on. In addition, the main department of government for HM's ADR will be needed.

• Molecular & Cellular Toxicology
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• v.3 no.2
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• pp.107-112
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• 2007

o-Nitrotoluene is used to synthesize artificial dyes and raw materials of urethane resin. In this study, we have carried out in vitro genetic toxicity tests and microarray analysis to understand the underlying mechanisms and the mode of action of toxicity of onitrotoluene. TA1535 and TA98 cells were treated with o-nitrotoluene to test its toxicity by basic genetic toxicity test. Ames and two new in vitro micronucleus and COMET assays were applied using CHO cells and L5178Y cells, respectively. In addition, microarray analysis of differentially expressed genes in L5178Y cells in response to o-nitrotoluene was analyzed using Affymatrix genechip. The result of Ames test was that o-nitrotoluene treatment did not increase the mutations both in base substitution strain TA1535 and in frame shift TA98. o-Nitrotoluene has not increased micronuclei in CHO cells. But onitrotoluene increased DNA damage in L5178Y cell. Two-hundred two genes were initially selected as differentially expressed genes in response to o-nitrotoluene by microarray analysis and forty four genes among them were over 2 times of log fold changed. These forty four genes could be candidate biomarkers of genetic toxic action of o-nitrotoluene related to induction of mutation and/or induction of micronuclei and DNA damage. Further confirmation of these candidate markers related to the DNA damage will be useful to understand the detailed mechanism of action of o-nitrotoluene.

• Molecular & Cellular Toxicology
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• v.3 no.2
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• pp.90-97
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• 2007

8-Hydroxyquinoline is used as antibacterial agent and antioxidant based on its function inducing the chelation of ferrous ion present in host resulting in production of chelated complex. This complex being transported to cell membrane of bacteria and fungi exerts antibacterial and antifungal action. In this study, we have carried out in vitro genetic toxicity tests and microarray analysis to understand the underlying mechanisms and the mode of action of toxicity of 8-hydroxyquinoline. TA1535 and TA98 cells were treated with 8-hydroxyquinoline to test its toxicity by basic genetic toxicity test, Ames and two new in vitro micronucleus and COMET assays were applied using CHO cells and L5178Y cells, respectively. In addition, microarray analysis of differentially expressed genes in L5178Y cells in response to 8-hydroxyquinoline were analyzed using Affymatrix genechip. The result of Ames test was that 8-hydroxyquinoline treatment increased the mutations in base substitution strain TA1535 and likewise, 8-hydroxyquinoline also increased mutations in frame shift TA98. 8-Hydroxyquinoline increased micronuclei in CHO cells and DNA damage in L5178Y. 8-Hdroxyquinoline resulted in positive response in all three tests showing its ability to induce not only mutation but also DNA damage. 783 Genes were initially selected as differentially expressed genes in response to 8-hydroxyquinoline by microarray analysis and 34 genes among them were over 4 times of log fold changed. These 34 genes could be candidate biomarkers of genetic toxic action of 8-hydroxyquinoline related to induction of mutation and/or induction of micronuclei and DNA damage. Further confirmation of these candidate markers related to their biological function will be useful to understand the detailed mode of action of 8-hydroxyquinoline.

• Journal of the Korean Chemical Society
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• v.53 no.6
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• pp.653-662
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• 2009

Developing effective tools for predicting absorption, distribution, metabolism, excretion properties and toxicity (ADME/T) of new chemical entities in the early stage of drug design is one of the most important tasks in drug discovery and development today. As one of these attempts, support vector machines (SVM) has recently been exploited for the prediction of ADME/T related properties. However, two problems in SVM modeling, i.e. feature selection and parameters setting, are still far from solved. The two problems have been shown to be crucial to the efficiency and accuracy of SVM classification. In particular, the feature selection and optimal SVM parameters setting influence each other, which indicates that they should be dealt with simultaneously. In this account, we present an integrated practical solution, in which genetic-based algorithm (GA) is used for feature selection and grid search (GS) method for parameters optimization. hERG ion-channel inhibitor classification models of ADME/T related properties has been built for assessing and testing the proposed GA-GS-SVM. We generated 6 different models that are 3 different single models and 3 different ensemble models using training set - 1891 compounds and validated with external test set - 175 compounds. We compared single model with ensemble model to solve data imbalance problems. It was able to improve accuracy of prediction to use ensemble model.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2004.05a
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• pp.25-26
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• 2004

• Proceedings of the Korean Society of Toxicology Conference
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• 2004.05a
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• pp.25-26
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• 2004

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.10
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• pp.4271-4274
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• 2014

The epithelial to mesenchymal transition (EMT) is a key step during embryonic morphogenesis and plays an important role in drug resistance and metastasis in diverse solid tumors. We previously reported that 48 h treatment of anti-cancer drug doxorubicin could induce EMT in human gastric cancer BGC-823 cells. However, the long term effects of this transient drug treatment were unknown. In this study we found that after 48 h treatment with $0.1{\mu}g/ml$ doxorubicin, most cells died during next week, while a minor population of cells survived and formed colonies. We propagated the surviving cells in drug free medium and found that these long term cultured drug survival cells (abbreviated as ltDSCs) retained a mesenchymal-like cell morphology, and expressed high levels of EMT-related molecules such as vimentin, twist and ${\beta}$-catenin. The expression of chromatin reprogramming factors, Oct4 and c-myc, were also higher in ltDSCs than parental cells. We further demonstrated that the protein level of p300 was upregulated in ltDSCs, and inhibition of p300 by siRNA suppressed the expression of vimentin. Moreover, the ltDSCs had higher colony forming ability and were more drug resistant when compared to parental cells. Our results suggested that an epigenetic mechanism is involved in the EMT of ltDSCs.

• Korean Journal of Pharmacognosy
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• v.22 no.2
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• pp.112-123
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• 1991

Traditional drugs(herbal and animal drugs) of Korea, China and Japan have developed essentially from the same origin, since the traditional medicine of three countries has been originated from ancient China. Due to different geographical locations and discrepancy of plant resources of the traditional drugs, some divergency in terms of systematic botany in traditional drug materials has appeared in the three countries. Present report aims to survey traditional herbal drugs that have been called same traditional names in three countries, but they are actually different with respect to systematic botanical view-point. The official drug compendia(pharmacopoeia and natural drug standards) of three countries were subject to examination. Survey was conducted by the following categories. Traditional drugs were listed under same name, however, 1) they belong to different genus; 7 traditional herbal drugs were listed. 2) they belong to same genus, but different species; 24 traditional herbal drugs were found. 3) a variety of related species are used; 15 traditional drugs were listed. 4) actually same plant, but taxonomical name is differently called and/or different parts of plant are used; 10 traditional drugs were counted. 5) animal drugs belong to one of the above categories; 7 traditional animal drugs were found. Total 63 traditional drugs(herbal and animal) were found to comprise different taxonomical names when the official drug compendia of Korea, China and Japan were examined.

• The Journal of Korean Medicine
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• v.18 no.2
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• pp.148-154
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• 1997

In the pharmacology of traditional Korean medicine, each drug has its own specific characters. The different characters of drugs are employed to treat diseases, rectify the hyperactivity or hypoactivity of yin or yang, and help the body restore its normal physiological functions, consequently curing the diseases and restoring health. The various characters and functions of these drugs concerning medical treatment include drugs' properties, flavours, actions of lifting, lowering, floating and sinking, channel tropism, toxicity, etc. Among these theories, theory of properties and flavours of drugs provides the basis for drug analysis and application. 'Property' refers to the cold, hot, warm or cool nature of a drug. These properties of drugs are so sorted out according to the different actions of the drugs on the human body and thier therapeutic effects. Drugs which cure heat syndrome(yang syndrome) have a cold or cool property, whereas drugs which cure cold syndrome (yin syndrome) have hot or warm property Drugs of cold and cool-natured and drugs of warm and hot natures are of opposite properties. A cold-natured drug is different from a cool-natured on only in degree, and so is a warm-natured drug from a hot-natured drug. Most of the cool- or cold- natured drugs have the effects of clearing heat, purging fire, removing toxic substances, and nourishing yin, and are uese to cure heat syndromes. On the contrary, drugs of warm or hot nature usually have the effects of dispersing cold, warming up the interior, supporting yang, and treating collapse, and are therefore used to treat cold syndromes. We thought that the property of drug may be related to the autonomic nervous system in western medicine. In other words, drugs of warm or hot nature increase heart rate or acts like sympathomimetics, and drugs of cool or cold nature decrease heart rate or acts like para sympathomimetics . According to this hypothesis, we administrated some drugs to isolated rat right atrium in magnus tube. But there is no correlation between 'property' in traditional Korean medicine and autonomic nervous system in western medicine.

• Journal of The Korean Society of Clinical Toxicology
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• v.7 no.2
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• pp.172-175
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• 2009

Zipeprol dihydrochloride is a non-opioid mucolytic, antitussive agent and it is frequently prescribed for respiratory symptoms such as cough and sputum. The main pharmacologic mechanisms of zipeprol are inhibition of superior laryngeal nerve stimulation and direct antagonism for stimulation of the bronchial receptors, which might have an effect for the drug's mucolytic action. Many cases of drug abuse with zipeprol have occurred world-wide due to the hallucinogenic effect of the drug. In Korea, zipeprol was reported to be the most commonly abused drug among young people for the 1990s. Zipeprol associated death was first reported since 1991 and 69 cases of death related to zipeprol abuse were further reported during 8 years (between 1991 and 1998). In addition to the hallucinogenic effect, dyspnea, extrapyramidal symptoms, seizure, cerebral edema have been reported as the signs and symptoms of toxic zipeprol overdose. However, zipeprol abuse is not common for old age people and non drug abusers. We report here on a fatal case of acute zipeprol poisoning in an eighty five year old drug addicted woman.