• 대한임상독성학회지
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• 제3권2호
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• pp.93-98
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• 2005

Purpose: This study was to investigate the resuscitation outcomes and the clinical characteristics of non-traumatic drug-induced out-of-hospital cardiac arrest by analyzing data from a single institution's registry. Method: We conducted a retrospective study of 795 patients who came to the emergency department with non-traumatic drug-induced out-of-hospital cardiac arrest during the period $1991{\~}2004$. Only patients over 18 years of age were included. Clinical characteristics. variables associated with cardiac arrest, and data during resuscitation were obtained from our cardiac arrest database. Patients were divided into two groups: drug-induced cardiac arrest (drug group, n=33), and non drug-induced cardiac arrest (non-drug group, n=762). Results: Spontaneous circulation was restored in 23 ($72{\%}$) patients in the drug group and in 314 ($45{\%}$) patients in the non-drug group ($x^2=0.020$). The patients who discharged alive number were 46 ($6{\%}$) in the non-drug group and 0 ($0{\%}$) in the drug group ($x^2=0.005$). The witnessed arrest, the epinephrine doses, and total defibrillation energy were not different between two groups. Conclusion: The return of spontaneous circulation rate was higher in the drug group than the non-drug group. However the drug group was lower survival discharge rate than in the non-drug group.

• Biomolecules & Therapeutics
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• 제15권4호
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• pp.252-260
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• 2007

As it is needed to assay possible feasibility of extrapolation between in vivo and in vitro systems and to develop a new in vitro method for toxicity testing, we investigated global gene expression from both animal and cell line treated with thioacetamide (TAA) and compared between in vivo and in vitro genomic profiles. For in vivo study, mice were orally treated with TAA and sacrificed at 6 and 24 h. For in vitro study, TAA was administered to a mouse hepatic cell line, BNL CL.2 and sampling was carried out at 6 and 24 h. Hepatotoxicity was assessed by analyzing hepatic enzymes and histopathological examination (in vivo) or lactate dehydrogenase (LDH) assay and morphological examination (in vitro). Global gene expression was assessed using microarray. In high dose TAA-treated group, there was centrilobular necrosis (in vivo) and cellular toxicity with an elevation of LDH (in vitro) at 24 h. Statistical analysis of global gene expression identified that there were similar numbers of altered genes found between in vivo and in vitro at each time points. Pathway analysis identified several common pathways existed between in vivo and in vitro system such as glutathione metabolism, bile acid biosynthesis, nitrogen metabolism, butanoate metabolism for hepatotoxicty caused by TAA. Our results suggest it may be feasible to develop toxicogenomics biomarkers by comparing in vivo and in vitro genomic profiles specific to TAA for application to prediction of liver toxicity.

• 대한한방내과학회지
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• 제40권6호
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• pp.1035-1042
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• 2019

Background: Herbal medication is widely used in the Korean Medicine Hospital, and drug-induced liver injury (DILI) in Korea has increased proportionally. Herb-induced liver injury now accounts for approximately 40% of cases of hepatotoxicity in Korea, according to research data. Currently, however, the component responsible for the toxicity is usually unknown or can only be suspected. Objective: To study the hepatotoxicity of Cheongsimyeonja-tang in DILI. Methods: A retrospective review was conducted of 82 inpatients between April 2010 and March 2017 with suspected drug-induced liver injury (n=5). The standard criteria (RUCAM scale) for drug-induced liver injury (DILI) were applied. The electronic medical records (EMRs) were retrospectively reviewed to identify the relevant database. Aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin (T. Bili) were analyzed in blood samples before and after the administration of Cheongsimyeonja-tang. Results: Five cases out of 82 patients had a criterion-referenced probable (RUCAM) score ranging from 6 to 8 points DILI. However, statistical analysis of the liver function parameters results of the 82 patients did not show a statistically meaningful elevation after taking Cheongsimyeonja-tang. Conclusions: These data suggest a relationship between Cheongsimyeonja-tang and DILI. More studies are needed to validate these observations and to explore their implications.

• Tuberculosis and Respiratory Diseases
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• 제63권5호
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• pp.435-439
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• 2007

PZA에 의한 독성 간염은 약 2% 정도 보고되고 있으나 전격성 간염으로 진행하여 사망하는 경우는 드물게 보고되고 있다. 본 증례에서는 항결핵제에 의해 중증 독성 간염을 보였다가 회복된 후 저용량의 PZA을 재투여 하고 전격성 간염으로 진행하는 양상을 보였다. 이번 사례를 통해 저용량의 PZA를 투약시 전격성 간부전으로 진행하는 경우를 경험했고 항결핵제 투여시 면밀한 관찰이 필요하고 항결핵 약제 투여시 신중을 기울여야겠다.

• 한국임상약학회지
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• 제29권4호
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• pp.223-230
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• 2019

Background: Small-molecule tyrosine kinase inhibitors (TKIs) have had major impacts on anticancer therapy by targeting the catalytic activities of dysregulated tyrosine kinases. TKIs have not presented traditional toxicities; however, some serious adverse effects, including hepatotoxicity, have been documented in clinical trials and post-marketing surveillance. Although TKI-induced hepatotoxicity can cause severe clinical complications in patients, the underlying mechanism is still unclear. Methods: Studies on TKI-induced hepatotoxicity were identified by Pubmed search, and relevant articles were reviewed. Results: Immunoallergic reaction, cytochrome P (CYP) 450 polymorphisms, and formation of reactive metabolites are under consideration as mechanisms of TKI-induced hepatotoxicity. Host protein-drug metabolite conjugates are recognized as antigens by class II major histocompatibility complexes and are believed to cause liver injuries. Polymorphisms in CYP, which influences TKI metabolism, can slow TKI metabolism and may induce development of hepatotoxicity. The formation of reactive metabolites during drug metabolism can induce hepatotoxicity by directly causing cytotoxicity, leading to cell dysfunction, and indirect toxicity by mediating secondary immune reactions. Concurrent use of various medications with TKI can also cause hepatotoxicity by affecting drug transporter or enzyme activities. Conclusion: Periodic monitoring of patients taking TKIs and risk/benefit reassessments though post marketing surveillance are necessary to prevent hepatotoxicity.

• Tuberculosis and Respiratory Diseases
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• 제53권6호
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• pp.662-672
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• 2002

Amiodarone 폐독성은 약제 복용력이 있는 환자에서 새로운 증상과 X-선의 변화가 있을 때 의심하여야 하며 울혈성 심부전이나 폐감염증, 폐색전증, 악성종양 등과 감별하는 것이 중요하다. 진단은 임상적, 방사선학적, 조직학적 소견을 종합하여 내릴 수 있으며 대부분의 경우에는 약제 중단을 통해서 폐독성의 호전을 기대할 수 있으나 일부에서는 호흡부전으로 진행하거나 기존의 심부정맥의 재발 등으로 인하여 사망하는 경우도 있다. 저자들은 심부정맥으로 amiodarone을 사용하던 환자에서 치명적인 폐독성이 발생한 4예를 경험하였기에 이를 문헌고찰과 함께 보고하는 바이다.

• BMB Reports
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• 제48권5호
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• pp.256-265
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• 2015

Cardiovascular and neurodegenerative diseases are major health threats in many developed countries. Recently, target tissues derived from human embryonic stem (hES) cells and induced pluripotent stem cells (iPSCs), such as cardiomyocytes (CMs) or neurons, have been actively mobilized for drug screening. Knowledge of drug toxicity and efficacy obtained using stem cell-derived tissues could parallel that obtained from human trials. Furthermore, iPSC disease models could be advantageous in the development of personalized medicine in various parts of disease sectors. To obtain the maximum benefit from iPSCs in disease modeling, researchers are now focusing on aging, maturation, and metabolism to recapitulate the pathological features seen in patients. Compared to pediatric disease modeling, adult-onset disease modeling with iPSCs requires proper maturation for full manifestation of pathological features. Herein, the success of iPSC technology, focusing on patient-specific drug treatment, maturation-based disease modeling, and alternative approaches to compensate for the current limitations of patient iPSC modeling, will be further discussed. [BMB Reports 2015; 48(5): 256-265]

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4597-4606
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• 2012

Cholangiocarcinoma (CCA) is an uncommon adenocarcinoma which arises from the epithelial cells of the bile ducts. The aim of the study was to investigate the cytotoxicity, toxicity, and anticancer activity of a crude ethanolic extract of ginger (Zingiber officinale Roscoe) against CCA. Cytotoxic activity against a CCA cell line (CL-6) was assessed by calcein-AM and Hoechst 33342 assays and anti-oxidant activity was evaluated using the DPPH assay. Investigation of apoptotic activity was performed by DNA fragmentation assay and induction of genes that may be involved in the resistance of CCA to anticancer drugs (MDR1, MRP1, MRP2, and MRP3) was examined by real-time PCR. To investigate anti-CCA activity in vivo, a total of 80 OV and nitrosamine (OV/DMN)-induced CCA hamsters were fed with the ginger extract at doses of 1000, 3000, and 5000 mg/kg body weight daily or every alternate day for 30 days. Control groups consisting of 10 hamsters for each group were fed with 5-fluorouracil (positive control) or distilled water (untreated control). Median $IC_{50}$ (concentration that inhibits cell growth by 50%) values for cytotoxicity and anti-oxidant activities of the crude ethanolic extract of ginger were 10.95, 53.15, and $27.86{\mu}g/ml$, respectively. More than ten DNA fragments were visualized and up to 7-9 fold up-regulation of MDR1 and MRP3 genes was observed following exposure to the ethanolic extract of ginger. Acute and subacute toxicity tests indicated absence of any significant toxicity at the maximum dose of 5,000 mg/kg body weight given by intragastric gavage. The survival time and survival rate of the CCA-bearing hamsters were significantly prolonged compared to the control group (median of 54 vs 17 weeks). Results from these in vitro and in vivo studies thus indicate promising anticancer activity of the crude ethanolic extract of ginger against CCA with the absence of any significant toxicity. Moreover, MDR1 and MRP3 may be involved in conferring resistance of CCA to the ginger extract.

• Molecular & Cellular Toxicology
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• 제3권3호
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• pp.177-184
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• 2007

As a possible feasibility of the extrapolation between in vivo and in vitro systems, we investigated the global gene expression from both mouse liver and mouse hepatic cell line treated with hepatotoxic chemical, acetaminophen (APAP), and compared between in vivo and in vitro genomic profiles. For in vivo study, mice were orally treated with APAP and sacrificed at 6 and 24 h. For in vitro study, APAP were administered to a mouse hepatic cell line, BNL CL.2 and sampling was carried out at 6 and 24 h. Hepatotoxicity was assessed by analyzing hepatic enzymes and histopathological examination (in vivo) or lactate dehydrogenase (LDH) assay and morphological examination (in vitro). Global gene expression was assessed using microarray. In high dose APAPtreated group, there was centrilobular necrosis (in vivo) and cellular toxicity with the elevation of LDH (in vitro) at 24 h. Statistical analysis of global gene expression identified that there were similar numbers of altered genes found between in vivo and in vitro at each time points. Pathway analysis identified glutathione metabolism pathway as common pathways for hepatotoxicty caused by APAP. Our results suggest it may be feasible to develop toxicogenomics biomarkers or profiles by comparing in vivo and in vitro genomic profiles specific to this hepatotoxic chemical for application to prediction of liver toxicity.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
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• pp.142-142
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• 1998

This study has been undertaken to examine the effect of biphenyl dimethyl dicarboxylate (DDB) on rat liver drug metabolizing enzyme in order to understand the mechanism of DDB on improving hepatic toxicity in rat liver. After DDB was administered into male rats for different periods of time, mRNA level of CYP1A1 and CYP2B1 was measured by polymerase chain reaction (PCR). DDB treatment resulted in increase in CYP2B1 mRNA level whereas there was no change in CYP1A1 mRNA level. This effect of DDB was time dependent reaching maximal level by 2-day treatment. DDB dose response study showed that 50mg/kg DDB induced CYP2B1 mRNA to maximal level and DDB icreased CYP2B1 gene expression with dose-dependent manner. Based on studies of lipid peroxidation, serum ALT and AST levels and histopathologic examination showed DDB protection on CCl4 induced hepatotoxiccity.