• 대한예방한의학회지
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• 제19권3호
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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.

• 대한임상검사과학회지
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• 제51권3호
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• pp.370-378
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• 2019

허혈 재관류 손상은 기관 이식, 외과적 혈관 재개통 및 출혈시에 발생하며 조직 및 기관 기능 장애를 유발한다. 최근 허혈 재관류 손상의 기전적 연구를 위해 간장 허혈 모델을 많이 이용하고 있다. 본 연구는 허혈 재관류 랫드 모델을 이용하여 항산화와 항염증 효과를 가진 것으로 알려진 Vanillin에 의한 간장 및 신장 손상에 대한 보호 효과를 알아보고 관련된 기전을 조사하기 위하여 실시하였다. 시험물질은 각각 100 mg/kg의 농도로 3일간 투여한 후, 60분동안 간을 결찰하여 허혈 재관류를 유도하여 관찰하였으며, 음성대조군, sham대조군 및 허혈재관류만 실시한 허혈 재관류대조군을 따로 두어, 약물투여군과 비교하였다. Vanillin 처치군에서는 AST, ALT 활성이 허혈 재관류대조군에 비해 유의하게 억제되었고, 조직병리학적 관찰에서도 염증 부분과 괴사부분이 현저하게 감소하였다. MDA와 SOD는 허혈 재관류군에 비해 유의적인 변화를 보였다. 이상의 결과를 종합하면 Vanillin은 간장 허혈 재관류에 의한 세포염증 및 세포괴사를 완화시켜 간세포 보호작용을 나타내었고, 신장의 사구체 및 원위세뇨관에 염증 변화를 완화 시키고 있어 세포 손상을 방어하는 것으로 생각되며, 이러한 방어효과는 항산화 기능에 의한 영향으로 사료된다.

• 한국한의학연구원논문집
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• 제8권2호통권9호
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• pp.95-107
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• 2002

Yukmijihwang-tang(YM) is a noted herbal prescription in Chinese and Korean traditional medicines, and it has been known to reinforce the vital essence and has been widely used for a variety of disease such as stroke, osteoporosis, anti-tumor, and hypothyrodism. Regarding its traditional use, YM has been known to reinforce the Yin (vital essence) of liver and kidney. Also it has been known to reinforce nutrition and biological function in brain. Recently, studies suggested that YM increase antioxidant activities and exert the protective effect against oxidant-induced liver cell injury. We investigated the high-throughput gene expression analysis on the Yukmijihwang-tang administrated in SD rats. Microarray data were validated on a limited number of genes by semiquantitative RT-PCR and Western blot analyses. The recent availability of microarrays provides an attractive strategy for elaborating an unbiased molecular profile of large number of genes in drug discovery This experimental approach offers the potential to identify molecules or cellular pathways not previously associated with herbal medicine. Total RNA from normal control brain and Yukmijihwang-tang administrated brain were hybridized to microarrays containing 10,000 rat genes. The 52 genes were found to be up-regulated(twice or more) excluding EST gene. The nine genes were found to be down-regulated(twice or more) excluding EST gene. Gene array technology was used to identify for the first time many genes expression pathway analysis that arecell cycle pathway, apoptosis pathway, electron transport chain pathway, cytoplasmic ribosomal protein pathway, fatty acid degradation pathway, and TGF-beta signaling pathway. These differentially expressed genes pathway analysis have not previously been iavestigated in the context of herbal medicine efficacy and represent novel factors for further study of the mechanism of herbal medicine efficacy.

• Journal of health informatics and statistics
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• 제43권4호
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• pp.329-335
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• 2018

Objectives: In recent years, there has been an increased need for a way to extract desired information from multiple medical literatures at once. This study was conducted to confirm the usefulness of unstructured data analysis using previously published medical literatures to search for new indications. Methods: The new indications were searched through text mining, network analysis, and topic modeling analysis using 5,057 articles of atorvastatin, a treatment for hyperlipidemia, from 1990 to 2017. Results: The extracted keywords was 273. In the frequency of text mining and network analysis, the existing indications of atorvastatin were extracted in top level. The novel indications by Term Frequency-Inverse Document Frequency (TF-IDF) were atrial fibrillation, heart failure, breast cancer, rheumatoid arthritis, combined hyperlipidemia, arrhythmias, multiple sclerosis, non-alcoholic fatty liver disease, contrast-induced acute kidney injury and prostate cancer. Conclusions: Unstructured data analysis for discovering new indications from massive medical literature is expected to be used in drug repositioning industries.

• Parasites, Hosts and Diseases
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• 제54권2호
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• pp.155-161
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• 2016

Toxoplasma gondii is an important opportunistic pathogen that causes toxoplasmosis, which has very few therapeutic treatment options. The most effective therapy is a combination of pyrimethamine and sulfadiazine; however, their utility is limited because of drug toxicity and serious side effects. For these reasons, new drugs with lower toxicity are urgently needed. In this study, the compound, (Z)-1-[(5-nitrofuran-2-yl)methyleneamino]-imidazolidine-2,4-dione (nitrofurantoin), showed anti-T. gondii effects in vitro and in vivo. In HeLa cells, the selectivity of nitrofurantoin was 2.3, which was greater than that of pyrimethamine (0.9). In T. gondii-infected female ICR mice, the inhibition rate of T. gondii growth in the peritoneal cavity was 44.7% compared to the negative control group after 4-day treatment with 100 mg/kg of nitrofurantoin. In addition, hematology indicators showed that T. gondii infection-induced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, biochemical parameters involved in liver injury, were reduced by nitrofurantoin significantly. Moreover, nitrofurantoin exerted significant effects on the index of antioxidant status, i.e., malondialdehyde (MDA) and glutathione (GSH). The nitrofurantoin-treated group inhibited the T. gondii-induced MDA levels while alleviating the decrease in GSH levels. Thus, nitrofurantoin is a potential anti-T. gondii candidate for clinical application.

• Archives of Pharmacal Research
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• 제27권5호
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• pp.531-538
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• 2004

Ginsan, a polysaccharide isolated from Panax ginseng, has been shown to be a potent immunomodulator, producing a variety of cytokines such as TNF-a, IL-1$\beta$, IL-2, IL-6, IL-12, IFN-${\gamma}$ and GM-CSF, and stimulating lymphoid cells to proliferate. In the present study, we analyzed some immune functions 1$^{st}$-5$^{th}$ days after ginsan i.p. injection, including the level of non-protein thiols (NPSH) as antioxidants, heme oxygenase (HO) activity as a marker of oxidative stress, zoxazolamine-induced paralysis time and level of hepatic cytochrome P-450 (CYP450) as indices of drug metabolism system, and activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, and albumin level as indicators of hepatotoxicity. Ginsan in the dose of 100 mg/kg caused marked elevation (1.7-2 fold) of HO activity, decrease of total CYP450 level (by 20-34%), and prolongation of zoxazolamine-induced paralysis time (by 65-70%), and showed some differences between male and female mice. Ginsan treatment did not seem to cause hepatic injury, since serum AST, ALT, and ALP activities and levels of total bilirubin and albumin were not changed.d.

• 대한한의학방제학회지
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• 제16권1호
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• pp.117-130
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• 2008

Korean traditional medicine has been used for the treatment of the various diseases based on both oriental medicinal theory and clinical trials. Thus, the prescriptions of Korean traditional medicine would be useful for the development of new therapeutics. This research focuses on the fundamental study in Korean traditional prescriptions for the development of new hepatoprotective agents. We found two prescriptions. Injinho-Tang and Osumogwa-Tang, showed the significant DPPH free radical scavenging and hepatoprotective effect, respectively. It is well-known that free radical scavenging effect is related to the prevention of various pathological events including liver injury. This paper deals with hepatoprotective effects on tacrine-induced cytotoxicity in Hep G2 cells, free radicals scavenging on both DPPH and superoxide of above two prescriptions. Hot water extract of Injinho-Tang did not show the significant hepatoprotective effect on tacrine-induced cytotoxicity in Hep G2 cells, however, it shows the significant scavenging effects for both DPPH and superoxide radicals. On the other hand, all of the hot water extracts of constituent herbal drugs in Injinho-Tang exhibited the promising protective effect on tacrine-induced cytotoxicity in Hep G2 cells. Of these, water extract of Rhei Rhizoma showed the most prominent effect on tacrine-induced cytotoxicity in Hep G2 cells. Bioassay-guided fractionation of Rhei Rhizoma extract has furnished four compounds, and their chemical structures have been identified by comparison of their spectral data with those of literature as chrysophanol (1), emodin (2), 3,5-dihydroxy-4'- methoxystilbene (3), and rhapontigenin (4), respectively. Among the isolated compounds, compounds 2-4 revealed the significant hepatoprotective effect in vitro when their $EC_{50}$ values compare with that of silybin, as a positive control. It also exhibited that emodin possessed the most hepatoprotective effect among these active compounds. In case of Osumogwa-Tang, its hot water extract showed the moderate protective effect on tacrine-induced cytotoxicity in Hep G2 cells. Hot water extract of Chaenomelis Fructus, one of the constituent herbal drug of this prescription, exhibited the significant hepatoprotective effect with $EC_{50}$ value of $7.8{\pm}0.1\;{\mu}g/ml$, however, it showed strong cytotoxicity in Hep G2 cells above the concentration of $25\;{\mu}g/ml$. It was revealed that both hot water extract of Evodiae Fructus and its butanol soluble fraction showed the moderate hepatoprotective effect but concentration-dependent activity in Hep G2 assay system. Two quinolone alkaloids, evocarpine and dihydroevocarpine, also tested for their hepatoprotective effects on tacrine-induced cytotoxicity in Hep G2 cells, however, these two compounds derived from the Evodiae Fructus as the major constituents did not show in vitro hepatoprotective effect. From these results, it would be necessary to further isolation of its hepatoprotective compounds from the butanol soluble fraction of the hot water extract of Evodiae Fructus.

• 한국임상수의학회지
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• 제28권6호
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• pp.549-554
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• 2011

FK506은 말기 간암환자의 간이식 후 널리 사용되는 면역억제제이다. Dexamethasone은 세포독성 암 치료에서 오심 방지, 정상세포의 보호와 기타 이유 등의로 빈번하게 병용처치된다. 본 연구의 목적은 간암세포주(Hep3B)에서 FK506의 항암효과와 FK506에 의한 항암효과에 대한 dexamethasone의 억제효과를 알아보기 위함이다. 세포의 손상은 세포 생존성 평가와 LDH 및 세포내 ROS 양의 측정으로 평가 하였다. 세포내 칼슘 농도([$Ca^{2+}$]i)와 JNK, Bax 단백질의 발현 정도도 평가하였다. FK506의 처치는 Hep3B의 세포사를 유도하였으며 세포생존성의 감소와 LDH, ROS 및 [$Ca^{2+}$]i 를 증가시켰다. FK506은 Bax와 JNK 의 활성을 증가시켰으며 Bcl-2의 활성을 억제하였다. Dexamethasone 처치 그 자체는 세포생존성, LDH와 ROS에 영향을 주지 않았다. 그러나 dexamethasone과 FK506의 병용처치는 FK506에 의한 LDH 방출, ROS 생성 및 JNK의 활성을 감소시켰다. 이 결과는 간암세포주에서 FK506은 항암효과를 가지지만 dexamethasone의 병용처치는 FK506에 의한 항암효과를 길항한다.

• Journal of Yeungnam Medical Science
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• 제34권1호
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• pp.123-127
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• 2017

Drug-induced immune hemolytic anemia (DIIHA) is a rare side effect of drugs. DIIHA may cause a systemic inflammatory response that results in acute multi-organ failure and death. Ceftizoxime belongs to the class of third generation cephalosporins, which are the most common drugs associated with DIIHA. Herein, we present a case of a 66-year-old man who developed fatal DIIHA after receiving a second dose of ceftizoxime. He was admitted to receive photodynamic therapy. He had a history of a single parenteral dose of ceftizoxime 3 months prior to admission. On the day of the procedure - shortly after the infusion of ceftizoxime - the patient's mental status was altered. The blood test results revealed hemolysis. Oliguric acute kidney injury developed, and continuous renal replacement therapy had to be applied. On the suspicion of DIIHA, the patient underwent plasmapheresis. Diagnosis was confirmed by a detection of drug-dependent antibody with immune complex formation. Although his hemolysis improved, his liver failure did not improve. He was eventually discharged to palliative care, and subsequently died.

• Journal of Acupuncture Research
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• 제33권3호
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• pp.197-205
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• 2016

Objectives : To report the clinical application and safety of Traditional Korean Medical treatment for patients with low back pain during pregnancy. Methods : Three patients who suffered from low back pain during pregnancy were treated with acupuncture, pharmacopuncture, moxibustion, and herbal medicine for 12 to 21 days. Numeric rating scale (NRS) of low back pain and Oswestry Disability Index (ODI) were checked to measure the outcome. A liver function and renal function test was carried out to identify any drug-induced liver or renal injury, and any adverse events were monitored thoroughly until delivery. Results : Low back pain reduced on NRS in all cases, and no serious adverse effects were found in the patients or infants. Conclusion : This study suggests that Traditional Korean Medical treatment is a candidate therapy for relieving low back pain during pregnancy, and also is safe for both patients and infants.