• Title/Summary/Keyword: Drug-associated

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Increased Interlenkin-2 Serum Level in Male Schizophrenic Patients (남자 정신분열증 환자에서 혈청 Interlenkin-2 농도의 증가)

  • Kim, Yong-Ku;Kim, Sa-Jun;Lee, Min-Soo
    • Korean Journal of Biological Psychiatry
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    • v.3 no.1
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    • pp.109-114
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    • 1996
  • We have previously reported that Korean schizophrenic patients hove low production of IL-2 in vitro suggestive of autoimmunity to the pathogenesis of the disorder. In an attempt to further explore this issue, we measured in vivo serum levels of interleukins(IL-$1{\beta}$, IL-2, and IL-6) using a quantitative "sandwich" enzyme immunoassay(ELISA) in 26 male schizophrenic patients and in 26 age-matched normal controls. Patients met DSM-IV criteria for schizophrenia and were drug free for at least six months. The severity of symptoms was assessed by SANS and SAPS. We found a significant increase of IL-2 level(p<0.05) in schizophrenic patients as compared with normal controls. There were significant positive correlations between IL-2, IL-6 levels and negative symptom scores. There were no correlations between age, age at onset, duration of illness and interleukin levels. Our results may support the hypothesis of viral-autoimmune dysfunction in schizophrenia. IL-2 or IL-6 may be associated with specific clinical feature in schizophrenic syndrome, especially negative symptom.

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Combined Treatment with 5-Fluorouracil and Capsaicin Induces Apoptosis in HT-29 Human Colon Cancer Cells (5-Fluorouracil과 Capsaicin의 병용에 의한 HT-29 대장암세포 사멸 증진 효과)

  • Lee, Yun-Seok;Lee, Jong-Suk;Kim, Jung-Ae
    • YAKHAK HOEJI
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    • v.53 no.4
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    • pp.184-188
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    • 2009
  • Fluorouracil (5-FU) is one of the most widely used chemotherapeutic drugs in the treatment of advanced colorectal cancer patients. Capsaicin (N-vanillyl-8-methyl-alpha-nonenamide), a spicy component of hot pepper, is a homovanillic acid derivative that preferentially induces cancer cells to undergo apoptosis. The purpose of the present study is to examine whether capsaicin enhances the anticancer effect of 5-fluorouracil in HT-29 human colon cancer cells by inducing apoptosis, and whether PPARgamma is involved in the capsaicin action in combination treatment with 5-FU. Treatment of the cells with either 5-FU or capsaicin alone for 48 h had little effect on the cell viability up to $50{\mu}M$ concentration, whereas co-treatment of the cells with capsaicin in the presence of 5-FU for 48 h significantly decreased the cell viability in a concentration-dependent manner. In addition, caspase-3 activity, a marker enzyme for apoptosis, was significantly increased by the combined treatment with 5-FU and capsaicin compared to the 5-FU or capsaicin alone treatment. Also, treatment with troglitazone, a peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) agonist, further enhanced the effect of the combination treatment on the cell viability and caspase-3 activity, and bisphenol A diglycidyl ether (BADGE), a $PPAR{\gamma}$ antagonist, blocked the effect of the combination treatment. These results suggest that the combination treatment of HT-29 cells with 5-FU and capsaicin induces apoptotic cell death at relatively low concentration than each drug alone, and the combination treatment may be associated with the $PPAR{\gamma}$ pathway activation.

Prediction of the Hepatotoxicity Risk Factor Induced by Antituberculosis Agents in Koreans (한국인의 항결핵제에 의한 간독성 위험인자 예측)

  • Lee, Ji-Sun;Kim, Hyun-Ah;Cho, Eun;Lee, Ok-Sang;Lim, Sung-Cil
    • YAKHAK HOEJI
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    • v.55 no.4
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    • pp.352-360
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    • 2011
  • Standard combination chemotherapy including isoniazid, rifampin, pyrazinamide, and ethambutol is very effective against tuberculosis. But, these medicines can cause hepatotoxicity which is the main reason for treatment interruption or change in drug regimen. In order to identify risk factors associated with hepatotoxcity in Koreans and assess elevated baseline LFTs' contributions to hepatotoxicity, a retrospective case control study was performed. The medical records of 277 patients who diagnosed with tuberculosis at a community hospital from January 1st, 2007 to June 30th, 2010 were reviewed. Patients were categorized into 3 groups (non toxic group, patients without increase in LFT levels; mild to moderate hepatotoxic group and severe hepatotoxic group). And the correlation between risk factors and hepatotoxicity was analyzed by using SPSS program. The overall incidence of hepatotoxicity was 18% and 8.7% of patients developed severe toxicity. Patients in the severe toxic group had the longest treatment period among the three groups. In 75% of severe toxic group, hepatotoxicity occurred within 18.3 days after starting medication. Hypoalbuminemia (serum albumin <3 g/dl) was a significant risk factor for development of severe toxicity. Elevated baseline transaminase (except ALT), total bilirubin, and preexisting hepatitis were also risk factors which were more than twice as likely to increase risk of severe hepatotoxicity (p>0.05). In conclusion, hypoalbuminemia (serum albumin level <3 g/dl) was a significant risk factor for anti-tuberculosis druginduced severe toxicity. Therefore, before starting antituberculosis chemotherapy, serum albumin level should be assessed at baseline. In high-risk patients (hypoalbuminemia, elevated LFTs) for hepatotoxicty, liver function should be closely monitored up to at least 21 days after taking medication.

Effects of Phenytoin and Diazepam on the Seizure Activity in the Cortical Dysplasia Animal Models

  • Kim, Si-Hyung;Choi, In-Sun;Cho, Jin-Hwa;Park, Eun-Ju;Jang, Il-Sung;Choi, Byung-Ju;Kim, Hyun-Jung;Kim, Young-Jin;Nam, Soon-Hyeun
    • International Journal of Oral Biology
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    • v.31 no.2
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    • pp.33-43
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    • 2006
  • Dysplasia-associated seizure disorders are markedly resistant to pharmacological intervention. Relatively little research has been conducted studying the effects of antiepileptic drugs(AEDs)on seizure activity in a rat model of dysplasia. We have used rats exposed to methylazoxymethanol acetate(MAM) in utero, an animal model featuring nodular heterotopia, to investigate the effects of AEDs in the dysplastic brain. Pilocarpine was used to induce acute seizure in MAM-exposed and age-matched vehicle-injected control animals. Field potential recordings were used to monitor amplitude and numbers of population spikes, and paired pulse inhibition in response to stimulation of commissural pathway. Two commonly used AEDs were tested: diazepam 5, 2.5 mg/kg; phenytoin 40, 60 mg/kg. Diazepam(DZP) and phenytoin(PHT) reduced the amplitude of population spike in control and MAM-exposed rats. However, the amplitude of population spike was nearly eliminated in control rats as compared to the MAM-exposed rats. Pharmaco-resistance was tested by measuring seizure latencies in awake rats after pilocarpine administration(320 mg/kg, i.p.) with and without pretreatment with AEDs. Pre-treatment with PHT 60 mg prolonged seizure latency in control rats, but not in MAM-exposed animals. The main findings of this study are that acute seizures initiated in MAM-exposed rats are relatively resistant to standard AEDs assessed in vivo. These data suggest that animal model with cortical dysplasia can be used to screen the effects of potential AEDs.

Combination Therapy of Gefitinib and Korean Herbal Medicines Could be a Beneficial Option for Patients with Non-Small-Cell Lung Cancer

  • Lee, Kangwook;Ryu, Juyoung;Son, Chang-Gue;Cho, Jung-Hyo;Yoo, Hwa-Seung;Lee, Jonghoon;Kim, Yoon-sik;Lee, Namhun
    • Journal of Pharmacopuncture
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    • v.19 no.3
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    • pp.259-263
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    • 2016
  • Lung cancer has a high mortality rate and is often diagnosed at the metastatic stage. Gefitinib is a targeted molecular therapeutic drug used to treat patients with non-small-cell lung cancer (NSCLC). Korean herbal medicines may also have therapeutic efficacy against lung cancer, reduce the side effects associated with chemotherapy, and improve patient quality of life (QOL). This case report describes the effects of a Korean herbal medicine regimen combined with gefitinib in a patient with NSCLC and bone metastasis. The Korean herbal medicine regimen included woohwanggeosa-dan, hwanggibujeong-dan and geonchilgyebok-jeong. The computed tomography (CT) findings showed that following combination treatment, the size of the tumor was markedly decreased without serious adverse events. Moreover, the Eastern Cooperative Oncology Group (ECOG) performance status was improved and cancer-related pain was decreased. These results suggest that a combination of Korean herbal medicines and gefitinib may be an effective therapeutic option for patients with advanced NSCLC and bone metastasis. Further studies are needed to examine the mechanism and the clinical efficacy of Korean herbal medicines against NSCLC.

Elimination of R-Plasmid in Streptomyces bobili (YS-40) by Ethldium Bromide (Ethidium Bromide에 의한 Streptomyces bobili(YS-40)의 R-Plasmid 제거)

  • 김상달;도재호
    • Microbiology and Biotechnology Letters
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    • v.10 no.4
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    • pp.289-295
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    • 1982
  • Streptomyces bobili (YS-40) isolated from soil was tested that it had drug resistance against penicillin, cephalosporin series antibiotics and other antibiotics in the previous paper. The treatment of Streptomyces bobili, (YS-40) with ethidium bromide (EtBr), acriflavine and sodium dodecyl sulfate. (SDS) resulted in the elimination of R-plasmid from the host strain. Minimum growth inhibitory concentrations (MIC) of Hg, Ag, penicillin-G, ampicillin, chloramphenicol, oxytetracycline, streptomycin and kanamycin were found to be 15, 10, > 3, 000, > 100, > 1, 000, > 100, < 5 and < 5$\mu\textrm{g}$/$m\ell$ respectively. Among the curing agents, EtBr was proved to be the most powerful compound for the elimination of R-plasmid in the strain and the elimination rate with EtBr(10$\mu\textrm{g}$/$m\ell$) was about 98%. Optimal pH to. the elimination of R-plasmid was pH 7.0 and the R-plasmid in the cells incubated for 24 hrs was proved to be eliminated most effectively. Aerial mass color, soluble pigment formation and reverse side color were reported to be often the plasmid associated characteristics of the R-plasmid bearing bacteria. But these characteristics of the uncured and cured Streptomyces bobili, (YS-40) showed no changes in the most of the pigment formation media tested in this work.

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Ethanol extract of Allium fistulosum inhibits development of non-alcoholic fatty liver disease

  • Hwang, Jin-Taek;Shin, Eun Ju;Chung, Min-Yu;Park, Jae Ho;Chung, Sangwon;Choi, Hyo-Kyoung
    • Nutrition Research and Practice
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    • v.12 no.2
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    • pp.110-117
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    • 2018
  • BACKGROUND/OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease and is closely associated with metabolic syndrome. In the present study, we observed the effect of ethanol extract of Allium fistulosum (EAF) on NAFLD and have suggested the possibility of using EAF as a natural product for application in the development of a treatment for NAFLD. MATERIALS/METHODS: The preventive effect on hepatic lipid accumulation was estimated by using an oleic acid (OA)-induced NAFLD model in vitro and a Western diet (high-fat high-sucrose; WD)-induced obese mouse model. Animals were divided into three groups (n = 7): normal diet group (ND), WD group, and WD plus 1% EAF group. RESULTS: EAF reduced OA-stimulated lipid accumulation in HepG2 cells in the absence of cellular cytotoxicity and significantly blocked transcriptional activation of sterol regulatory element-binding protein 1 and fatty acid synthase genes. Subsequently, we investigated these effects in vivo in mice fed either ND or WD in the presence or absence of EAF supplementation. In comparison to the ND controls, the WD-fed mice exhibited increases in body weight, liver weight, epididymal fat weight, and accumulation of fat in hepatocytes, and these effects were significantly attenuated by EAF supplementation. CONCLUSIONS: Allium fistulosum attenuates the development of NAFLD, and EAF elicits anti-lipogenic activity in liver. Therefore, EAF represents a promising candidate for use in the development of novel therapeutic drugs or drug combinations for the prevention and treatment of NAFLD.

The Inhibitory Effects of Ahnjeonbaekho-tang on FRTL-5 Cell Proliferation and Thyroxine Synthesis

  • Kang, Shin-Ik;Lee, Byung-Cheol;Ahn, Young-Min;Doo, Ho-Kyung;Ahn, Se-Young
    • The Journal of Internal Korean Medicine
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    • v.27 no.3
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    • pp.653-663
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    • 2006
  • Objective : Graves' disease, the most common cause of hyperthyroidism, is an autoimmune disorder associated with autoantibodies to the TSH receptor. The clinical features of Graves' disease are goiter and hypermetabolic symptoms induced by excessive hormones. Antithyroid drug therapy is the first-line treatment for Graves' disease in Korea, Japan and European countries. Yet in spite of a long period and high-dose of treatment, it is hard to achieve remission because of adverse effects, frequent recurrence and resistance to antithyroid drugs. Recently, it has been reported that the abnormal thyroid hormone and clinical symptoms of Graves' disease were reduced by Ahnjeonbaekho-tang (AJBHT). Methods : To investigate the effectiveness and action mechanism of AJBHT, we studied the influence of AJBHT on FRTL-5 thyroid cell proliferation, DNA synthesis and expression of T4, TSH, cAMP, Tg and TPO mRNA. Results : AJBHT significantly inhibited the FRTL-5 cell proliferation, DNA synthesis, T4 synthesis, cAMP production and the expression of Tg mRNA in comparison with control and MMI. Conclusions : These results suggest that AJBHT may inhibit the cell proliferation and DNA synthesis by regulating the cAMP, and suppress the T4 synthesis by modulating Tg mRNA expression and cAMP synthesis, and that it may be useful agent for treating the goiter and hormone abnormality of Graves' disease.

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Inhibitory Effect of Injinchunggan-tang(Yinchenqinggan-tang) on Fibrogenesis of Rat Hepatic Stellate Cells (인진청간탕(茵蔯淸肝湯)이 간성상세포의 섬유화 억제에 미치는 영향)

  • Lee, Hong-Ri;Kim, Young-Chul;Woo, Hong-Jung;Lee, Jang-Hoon
    • The Journal of Internal Korean Medicine
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    • v.30 no.1
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    • pp.74-84
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    • 2009
  • Objectives : This study was performed to investigate the anti-fibrogenic effect of Injinchunggan-tang on cultured rat hepatic stellate cells. Materials and Methods : Hepatic stellate cells(HSC-T6) were treated with various concentrations of Injinchunggan-tang extract for 24, 48, and 72 hours. The extraction was done with distilled water. After the treatment, cell viability, proliferation, procollagen levels and the mRNA of the TIMP-1, TIMP-2, and ASMA were measured by using MTT assay. BrdU assay, procollagen type I C-peptide EIA kit and RT-PCR. Results : The proliferation, mRNA expression and synthesis of collagen of the hepatic stellate cells were inhibited by Injinchunggan-tang treatment in a dose-dependent manner. This indicates the prescription has inhibitory effect on fibrogenesis of the liver by regulating the fibrogenesis associated genes in transcription. Cell viability was inhibited in time- and dose-dependent manners. It seemed that the drug should be used with sufficient dose to acquire treatment effect. Conclusion : These results suggest that Injinchunggan-tang is beneficial in the treatment of cirrhotic patients as well as for the patients with chronic hepatitis.

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Lamivudine Therapy Exacerbates Bilirubinemia in Patients Underlying Severely Advanced Hepatitis

  • Choi, Young Hee;Lee, Chang Ho;Ko, Myong Suk;Han, Hyun Joo;Kim, Sang Geon
    • Toxicological Research
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    • v.33 no.4
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    • pp.343-350
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    • 2017
  • Lamivudine belongs to the set of antiviral agents effective against hepatitis B virus infection. Given case reports on liver injuries after certain antiviral agent treatments, this study examined the effects of lamivudine on alanine aminotransferase (ALT) and total bilirubin (TB) using a medical system database. A total of 1,321 patients taking lamivudine alone or with others were evaluated using laboratory hits in an electronic medical system at Seoul National University Hospital from 2005 through 2011. The patients were grouped according to prior ALT results: G#1, ALT < 40 IU/L; G#2, 40 IU/L ${\leq}$ ALT < 120 IU/L; G#3, 120 IU/L ${\leq}$ ALT < 240 IU/L; and G#4, ALT ${\geq}$ 240 IU/L. In G#1 and G#2 patients, lamivudine or adefovir treatment decreased ALT and TB compared to prior values. In G#3 and G#4 patients with three times the upper limit of normal (ULN) ${\leq}$ ALT < 15 times the ULN, both ALT and TB were decreased after treatment with lamivudine alone, or adefovir following lamivudine therapy, indicating that lamivudine therapy ameliorated liver functions. However, in G#4 patients who experienced severely advanced hepatitis (ALT ${\geq}$ 15 times the ULN, or ${\geq}$ 600 IU/L), lamivudine augmented TBmax ($6.3{\rightarrow}13.3mg/dL$) despite a slight improvement in ALT ($839{\rightarrow}783IU/L$), indicative of exacerbation of bilirubinemia. Patients who used adefovir after lamivudine also showed a high incidence of hyperbilirubinemia when they experienced severely advanced hepatitis. Treatment with adefovir alone did not show the effect. In conclusion, lamivudine may increase the risk of hyperbilirubinemia in patients with severely advanced hepatitis, implying that caution should be exercised when using lamivudine therapy in certain patient populations.