• Title/Summary/Keyword: Drug response

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1-Furan-2-yl-3-Pyridine-2-yl-Propenone Inhibits TNF-${\apha}$-induced Intestinal Inflammation via Suppression of MCP-1 and IL-8 Expressions in HT-29 Human Colon Epithelial Cells (1-Furan-2-yl-3-pyridin-2-yl-propenone의 TNF-${\apha}$ 유도성 MCP-1과 IL-8의 발현 억제를 통한 장 상피세포 염증 억제효과)

  • Kim, Kyoung-Jin;Kim, Jong-Tae;Lee, Eung-Seok;Lee, Jong-Suk;Kim, Jung-Ae
    • YAKHAK HOEJI
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    • v.52 no.5
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    • pp.402-406
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    • 2008
  • Previously, we have shown that 1-furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) has an anti-inflammatory activity in a rat paw-edema model. In the present study, we investigated an inhibitory effect of FPP-3 on the tumor necrosis factor (TNF)-${\apha}$-induced inflammatory cytokine response in HT-29 human colon epithelial cells. Treatment with FPP-3 significantly prevented the TNF-${\apha}$-induced attachment of leukocytes to HT-29 colon epithelial cells, which is one of the pathologic hallmarks in colon inflammation. The effect of FPP-3 was markedly superior than that of 5-aminosalicylic acid (5-ASA), a commonly used drug for the treatment of inflammatory bowel disease (IBD). The pretreatment with FPP-3 inhibited TNF-${\apha}$- induced monocyte chemoattractant protein (MCP)-1, interleukin (IL)-8 mRNA expressions. In addition, FPP-3 significantly suppressed TNF-${\apha}$-induced nuclear factor (NF)-${\kappa}B$ transcription activity. These results demonstrate that FPP-3 modulates intestinal inflammation via suppressing the NF-${\kappa}B$ dependent expressions of MCP-1 and IL-8, and suggest that FPP-3 may be a valuable agent for the treatment of IBD.

Effects of Cordyceps militaris on Immune Activity (밀리타리스 동충하초(Cordyceps militaris)의 면역 활성에 미치는 영향)

  • Kang, In Soon;Kim, Hyeju;Lee, Tae Ho;Kwon, Yong Sam;Son, Miwon;Kim, Chaekyun
    • YAKHAK HOEJI
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    • v.58 no.2
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    • pp.81-90
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    • 2014
  • In order to determine the functional benefits of Cordyceps militaris in the immune system, we examined the immunomodulatory activities of C. militaris using an immunocompromised C57BL/6 mice, mouse spleen cells, RAW 264.7 macrophage cells, and A549 lung carcinoma cells. Mice were injected intraperitioneally with an immunosuppressive drug, cyclophosphamide, and then administered orally with 30, 100 and 300 mg/kg of 50% ethanol extract of C. militaris (CME 30, CME 100 and CME 300) for 14 days. CME increased splenocyte proliferation and natural killer (NK) cell activity compared to 3% hydroxypropyl methylcellulose-treated control mice. CME also increased the production of Th1 cytokines, IL-2 and TNF-${\alpha}$ in spleen cells isolated from CME-injected mice and in vitro, which suggested the enhanced cellular immunity in response to CME. CME also increased splenocyte proliferation, NK cell activity, and IL-2 and TNF-${\alpha}$ production compared to 1 ${\mu}M$ methotrexate-treated spleen cells in vitro. We examined whether C. militaris regulates the production of inflammatory mediators in LPS-stimulated RAW 264.7 cells. CME inhibited LPS-induced NO production and iNOS expression in a dose dependent manner, while COX-2 expression was remained unchanged. In addition, CME also has free radical scavenging activity, indicating its antioxidant activity. These results indicate that C. militaris enhances immune activity by promoting immune cell proliferation and cytokine production.

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.

Ursodeoxycholic Acid Inhibits Inflammatory Cytokine Expression in THP-1 Cells Infected with Aggregatibacter actinomycetemcomitans

  • Song, YuRi;Kim, SeYeon;Park, Mee Hee;Na, Hee Sam;Chung, Jin
    • International Journal of Oral Biology
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    • v.42 no.1
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    • pp.33-38
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    • 2017
  • Background: Periodontitis is an inflammatory disease characterized by the breakdown of tooth-supporting tissues, leading to tooth loss. Aggregatibacter actinomycetemcomitans are major etiologic bacterium causing aggressive periodontitis. Ursodeoxycholic acid (UDCA), a hydrophilic gall bladder acid, has been used as an effective drug for various diseases related to immunity. The aim of this study was to investigate the effect of UDCA on the inflammatory response induced by A. actinomycetemcomitans. Methods: A human acute monocytic leukemia cell line (THP-1) was differentiated to macrophage- like cells by treatment with phorbol 12-mystristate 13-acetate (PMA) and used for all experiments. The cytotoxic effect of UDCA was examined by MTT assay. THP-1 cells were pretreated with UDCA for 30 min before A. actinomycetemcomitans infection and the culture supernatant was analyzed for various cytokine production by ELISA. The effect of UDCA on bacterial growth was examined by measuring optical densities using a spectrophotometer. Results: UDCA showed no cytotoxic effect on THP-1 cells, up to $80{\mu}M$ Ed highlight: Please confirm technical meaning. UDCA pretreatment inhibited the A. actinomycetemcomitans-induced $IL-1{\beta}$, $TNF-{\alpha}$, and IL-17A secretion in a dose-dependent manner. UDCA also inhibited IL-21 production at $60{\mu}M$. The production of IL-12 and IL-4 was not influenced by A. actinomycetemcomitans infection. Conclusion: These findings indicate that UDCA inhibits the production of inflammatory cytokines involved in innate and Th17 immune responses in A. actinomycetemcomitans-infected THP-1- derived macrophages, which suggests its possible use for the control of aggressive periodontitis.

Anti-allergic effect of Okbyungpoongsan-Hap-Changijasan (옥병풍산합창이자산(玉屛風散合蒼耳子散)의 항알레르기 효능에 대한 연구)

  • Jung, Jin-Ki;Park, Yong-Ki
    • The Korea Journal of Herbology
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    • v.25 no.2
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    • pp.55-63
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    • 2010
  • Objectives : In this study, we investigated anti-allergic effect of Okbyeongpungsan-Hap-Changijasan (KOB01) in allergic rhinitis(AR) experimental animals and mast cells. Methods : The potential anti-allergic effect of KOB01 was investigated in a rat model of compound 48/80-induced systemic anaphylactic shock and a mouse of ovalbumin(OVA)-induced AR, and human mast cell line, HMC-1 culture. Each animals were divided into four groups: normal, control, KOB01-treated(100 and 200 mg/kg) and anti-histamine drug, dosodium cromoglycate (DSCG)-treated(50 mg/kg). Animals were orally treated with KOB01 and DSCG and intraperitoneally injected with compound 48/80($10\;{\mu}g/kg$) or sensitized with 0.1% OVA. The mortality and serum histamine levels were measured in compound 48/80-induced anaphylatic rats. The histological changes in nasal mucosa were investigated in OVA-induced AR mice. Also, mast cell degranulation was observed in compound 48/80-stimulated HMC-1 cells. Results : KOB01 increased mortality and significantly decreased serum histamine levels in compound 48/80-induced anaphylatic rats. The abnormal histological changes such as expansion of grandular cells and hypertrophy of epithelium in nasal mucosa of OVA-induced AR mice was improved by KOB01 treatment nearby a normal group. Therefore, KOB01 inhibited compound 48/80-induced degranulation in HMC-1 cells. Conclusions : These results indicate that KOB01 decrease allergic response through suppressing the mast cell activation in AR and suggest a potential role for KOB01 as a source of anti-allergic agents for use in allergic disorders including of AR.

Effects of Pregabalin in Primary Burning Mouth Syndrome Patients Unresponsive to Topical Clonazepam Treatment: A Retrospective Pilot Study

  • Heo, Jun-Young;Jeon, Jae-Woo;Ok, Soo-Min;Jeong, Sung-Hee;Ahn, Yong-Woo
    • Journal of Oral Medicine and Pain
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    • v.41 no.1
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    • pp.1-6
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    • 2016
  • Purpose: To investigate the efficacy of pregabalin for patients with primary burning mouth syndrome (BMS) who are unresponsive to topical clonazepam therapy. Methods: By searching the clinical electronic records from the Department of Oral Medicine, Pusan National University Dental Hospital from 2012 to 2014, a retrospective analysis was performed on patients with primary BMS who were treated with topical clonazepam therapy during this period. Of the patients who were unresponsive to this therapy, 19 patients who were subsequently treated with pregabalin were included in the study. A pain assessment was performed using the 11-point numerical rating scale at first visit, following topical clonazepam therapy, and again after pregabalin therapy. The treatment outcomes were statistically analyzed using the Wilcoxon signed rank test. Results: Following additional pregabalin administration, the mean pain score was slightly reduced. A total of 7 patients reported a marked response (>50% pain reduction), and 3 patients reported a slight reduction in pain. Pain reduction following pregabalin therapy was statistically significant (p<0.05). Conclusions: Pregabalin has a slight therapeutic effect on patients with primary BMS. Therefore, we recommend pregabalin as an alternative drug for BMS patients who are unresponsive to topical clonazepam therapy.

Studies on the Effect of Corilagin Isolated from Euphorbia helioscopia on Collagen-Induced Arthritis (II);CytokinesAnalysis of Collagen II Induced Arthritis Mice Model (택칠에서 분리한 Corilagin이 Collagen 유발 관절염에 미치는 영향 (II);Corilagin을 투여한 류마티스 관절염 유발 생쥐의 사이토카인 분석)

  • Shin, Sam-Kee;Chang, Jun-Pok;Doh, Eun-Soo
    • Korean Journal of Plant Resources
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    • v.21 no.4
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    • pp.336-340
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    • 2008
  • Corilagin (CRN) isolated from Euphorbia helioscopia as rheumatoid arthritis drug. CRN was medicated to the abdominal cavity of collagen induced arthritis (CIA) mice that was an animal model for rheumatoid arthritis and its effects on incidence and arthritis index were studied. The results were as folllows; It was exhibited that medicating corilagin inhibited the infiltration of activated T lymphocytes into an inflammatory joint. The production of IgG and IgM that were RF (rheumatoid factor) and inflammatory cytokine, IL-6 and $TNF-{\alpha}$were reduced. After measuring $IFN-{\gamma}$and IL-4, it was found that it was shifted into Th2 immune response as increasing in IL-4. After liver function test, studies on liver poisoning of AST/ALT should be continued.

High Performance Liquid Chromatographic Analysis of a New Proton Pump Inhibitor KR60436 and Its Active Metabolite O-Demethyl-KR60436 in Rat Plasma Samples Using Column-Switching

  • Lee, Hyun-Mee;Lee, Hee-Yong;Choi, Joong-Kwon;Lee, Hye-Suk
    • Archives of Pharmacal Research
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    • v.24 no.3
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    • pp.207-210
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    • 2001
  • A fully automated high performance liquid chromatography with column-switching was developed for the simultaneous determination of KR60436, a new reversible proton pump inhibitor, and its active metabolite O-Demethyl-KR60436 from rat plasma samples. Plasma sample (50$\mu$l) was directly introduced onto a Capcell Pak MF Ph-1 column ($10{\times}4$ mm I.D.) where primary separation was occurred to remove proteins and concentrate target Substances Using acetonitrile-Potassium Phosphate (PH 7, 0.1 M) (2 : 8, v/v). The drug molecules eluted from MF Ph-1 column were focused in an intermediate column ($10{\times}2$ I.D.) by the valve switching step. The substances enriched in intermediate column were eluted and separated on a Vydac 218MR53 column ($250{\times}3.2$ I.D.) using acetonitrilepotassium phosphate (pH 7, 0.02 M) (47:53, v/v) at a flow rate of 0.5 ml/min when the valve status was switched back to A position. The method showed excellent sensitivity (detection limit of 2 ng/ml) with small volume of samples ($50{\mu}$l), good precision and accuracy, and speed (total analysis time 24 min) without any loss in chromatographic efficiency. The response was linear ($r^2{\geq}0.797$) over the concentration range of 5-500 ng/ml.

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The Influences of Extremely Low Frequency Magnetic Fields on Drug-Induced Convulsion in Mouse

  • Sung, Ji-Hyun;Jeong, Ji-Hoon;Kim, Jeong-Soo;Choi, Tai-Sik;Park, Joon-Hong;Kang, Hee-Yun;Kim, Young-Sil;Kim, Dong-Suk;Sohn, Uy-Dong
    • Archives of Pharmacal Research
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    • v.26 no.6
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    • pp.487-492
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    • 2003
  • This study investigated the effects of extremely low frequency magnetic fields (ELF-MFs) on the sensitivity of seizure response to bicuculline, picrotoxin and NMDA in mice. The mice were exposed to either a sham or 20 G ELF-MFs for 24 hours. Convulsants were then administered i.p. at various doses. The seizure induction time and duration were measured and lethal dose ($LD_{50$}) and convulsant dose ($CD_{50}$) of the clonic and tonic convulsion were calculated. The analysis of glutamate, glycine, taurine and GABA of mouse brain was accomplished by HPLC. The mice exposed to ELF-MFs showed moderately higher $CD_{50}.{\;}LD_{50}$ and onset time on the bicuculline-induced seizure. However, the ELF-MFs did not influence them in the NMDA and picrotoxin-induced seizures. After the exposure to MFs exposure, the glutamate level was increased and GABA was decreased significantly in NMDA and picrotoxin-induced seizure. The level of glutamate and GABA were not changed by MFs in bicuculline-induced seizure. These results suggest that ELF-MFs may alter the convulsion susceptibility through GABAergic mechanism with the involvement of the level of glutamate and GABA.

The Effect of Herb-acupunctures of Bojoongiggi-tang (Buzhongyiqi-tang), Ginseng Radix, and Astragali Radix on Immune Responses in Rats (보중익기탕(補中益氣湯), 인삼(人蔘) 및 황(黃)기 약침(藥鍼)이 MTX로 약침(誘發)된 백서(白鼠)의 면역기능저하(免疫機能低下)에 미치는 영향(影響))

  • Kim, Jung-Hun;Park, Hi-Joon;Lee, Hyang-Sook;Lee, Hye-Jung
    • Journal of Pharmacopuncture
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    • v.3 no.2
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    • pp.79-97
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    • 2000
  • Objectives : To investigate the effects of herb-acupunctures of Qi tonification herbs or formula on the rat immune depression induced by an anticancer drug, methotrexate (MTX) Methods: Animals were divided into 5 groups; Normal control group was not given any treatment. Immune depression was induced by oral administration of 1mg/kg MTX b.i.d for 4 days in Control, Sample I, II, and III groups. We treated on CV 4 (Guanyuan) with saline, Bojoongiggi-tang (Buzhongyiqi-tang), Ginseng Radix and Astragali Radix herb-acupunctures in Control, Sample I, II, and Ill groups, respectively. In both blood and spleen, the assessment of CD4+ T-cell count, CD8+ T-cell count, CD4/CD8 T-cell ratio was performed. Results: Here we show that 3 herb- acupuncture groups have an influence, to some extent, on CD4+ and CD8+ T-cell counts and CD4/CD8 T-cell ratio in both blood and spleen. Astragali Radix herb-acupuncture, in particular, was found to have significantly increased CD4+ T-cell count in blood and CD4/CD8 T-cell ratio in blood and spleen. Conclusions: The results of this study suggest that herb-acupunctures of Bojoongiggi-tang (Buzhongyiqi-tang), Ginseng Radix and Astragali Radix may have an influence over rat immune depression induced by MTX.