• Title/Summary/Keyword: CCl$^4$

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The Pharmacokinetics of Nimodipine After Oral Administration in Rabbits with Hepatic Failure

  • Choi, Jun-Shik;Choi, In;Burm, Jin-Pil
    • Journal of Pharmaceutical Investigation
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    • v.36 no.1
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    • pp.19-22
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    • 2006
  • The pharmacokinetics of nimodipine, following a single 16 mg/kg oral dose, was investigated in rabbits with hepatic failure induced by 0.5 mL/kg (mild), 1.0 mL/kg (moderate) and 2.0 mL/kg (severe) of carbon tetrachloride $(CCl_{4}$ : olive oil = 20 : 80, v/v). The plasma concentrations of nimodipine were determined by a high performance liquid chromatographic assay. The levels of sGOT and sGPT in rabbits with mild $(86.2{\pm}29.0\;and\;98.5{\pm}33.1\;unit/dL)$, moderate $(168.1{\pm}61.2\;and\;196.2{\pm}66.0\;unit/dL)$ and severe $(292.7{\pm}82.2\;and\;314.2{\pm}99.8\;unit/dL)$ hepatic failure were significantly increased compared to the control $(38.0{\pm}10.1\;and\;32.4{\pm}10.2\;unit/dL)$. The area under the plasma concentration-time curve (AUC) of nimodipine was significantly increased in mild $(131.7{\pm}28.1%)$, moderate $(168.8{\pm}32.8%)$ and severe $(204.6{\pm}58.3%)$ carbon tetrachloride-induced hepatic failure rabbits compared to the control (100%) rabbits. The volume of distribution $(V_{d})$ and the total body clearance $(CL_{t})$ of nimodipine were significantly decreased in all hepatic failure groups. The elimination rate constant $(K_{el})$ of nimodipine was significantly decreased in moderate and severe carbon tetrachloride-induced hepatic failure rabbits. There was a correlation between sGOT (y= 1.01x+241, r=0.993) or sGPT (y=0.92x +243, r=0.997) value and the AUC of nimodipine in the rabbits with hepatic failure. These findings suggest that the hepatic metabolism of nimodipine was inhibited by carbon tetrachloride-induced hepatic failure rabbits, resulting in the decrese in $V_{d}$ and $CL_{t}$ of nimodipine in the rabbits with mild, moderate and severe hepatic failure.

Increased Lymphocyte Infiltration in Rheumatoid Arthritis Is Correlated with an Increase in LTi-like Cells in Synovial Fluid

  • Koo, Jihye;Kim, Soochan;Jung, Woong Jae;Lee, Ye Eun;Song, Gwan Gyu;Kim, Kyung-Su;Kim, Mi-Yeon
    • IMMUNE NETWORK
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    • v.13 no.6
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    • pp.240-248
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    • 2013
  • In this study, we compared the immune cell populations in rheumatoid arthritis (RA) synovial fluid, which shows lymphoid tissue-like structure, with those in tonsils, which are normal secondary lymphoid tissues. Firstly, we found that $CD4^-CD11b^+$ macrophages were the major population in RA synovial fluid and that B cells were the major population in tonsils. In addition, synovial fluid from patients with osteoarthritis, which is a degenerative joint disease, contained $CD4^+CD11b^+$monocytes as the major immune cell population. Secondly, we categorized three groups based on the proportion of macrophages found in RA synovial fluid: (1) the macrophage-high group, which contained more than 80% macrophages; (2) the macrophage-intermediate group, which contained between 40% and 80% macrophages; and (3) the macrophage-low group, which contained less than 40% macrophages. In the macrophage-low group, more lymphoid tissue inducer (LTi)-like cells were detected, and the expression of OX40L and TRANCE in these cells was higher than that in the other groups. In addition, in this group, the suppressive function of regulatory T cells was downregulated. Finally, CXCL13 expression was higher in RA synovial fluid than in tonsils, but CCL21 expression was comparable in synovial fluid from all groups and in tonsils. These data demonstrate that increased lymphocyte infiltration in RA synovial fluid is correlated with an increase in LTi-like cells and the elevation of the chemokine expression.

Wnt-C59 inhibits proinflammatory cytokine expression by reducing the interaction between β-catenin and NF-κB in LPS-stimulated epithelial and macrophage cells

  • Jang, Jaewoong;Song, Jaewon;Sim, Inae;Yoon, Yoosik
    • The Korean Journal of Physiology and Pharmacology
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    • v.25 no.4
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    • pp.307-319
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    • 2021
  • Dysregulation of the Wnt pathway causes various diseases including cancer, Parkinson's disease, Alzheimer's disease, schizophrenia, osteoporosis, obesity and chronic kidney diseases. The modulation of dysregulated Wnt pathway is absolutely necessary. In the present study, we evaluated the anti-inflammatory effect and the mechanism of action of Wnt-C59, a Wnt signaling inhibitor, in lipopolysaccharide (LPS)-stimulated epithelial cells and macrophage cells. Wnt-C59 showed a dose-dependent anti-inflammatory effect by suppressing the expression of proinflammatory cytokines including IL6, CCL2, IL1A, IL1B, and TNF in LPS-stimulated cells. The dysregulation of the Wnt/β-catenin pathway in LPS stimulated cells was suppressed by WntC59 treatment. The level of β-catenin, the executor protein of Wnt/β-catenin pathway, was elevated by LPS and suppressed by Wnt-C59. Overexpression of β-catenin rescued the suppressive effect of Wnt-C59 on proinflammatory cytokine expression and nuclear factor-kappa B (NF-κB) activity. We found that the interaction between β-catenin and NF-κB, measured by co-immunoprecipitation assay, was elevated by LPS and suppressed by Wnt-C59 treatment. Both NF-κB activity for its target DNA binding and the reporter activity of NF-κB-responsive promoter showed identical patterns with the interaction between β-catenin and NF-κB. Altogether, our findings suggest that the anti-inflammatory effect of Wnt-C59 is mediated by the reduction of the cellular level of β-catenin and the interaction between β-catenin and NF-κB, which results in the suppressions of the NF-κB activity and proinflammatory cytokine expression.

Bee Venom Within Liposomes Synergistically Inhibit Atopic Dermatitis in Mice

  • Kim, Joan;Song, Ho Sueb
    • Journal of Acupuncture Research
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    • v.39 no.1
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    • pp.40-48
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    • 2022
  • Background: This study was performed to determine the effects of liposome-encapsulated bee venom (BV) treatment of inflammatory factors in atopic dermatitis (AD) compared with BV treatment. Methods: AD was induced by phthalic anhydride in mice and the effects of BV liposomes were measured. Using Leica Application Suite, thickened epidermis and dermis were measured after BV liposome treatment (0.05 and 0.1 ㎍/mL). The number of stained mast cells and the concentration of immunoglobulin (Ig)E were measured. Serum IgE concentration was analyzed using an enzyme-linked immunosorbent assay. The serum concentrations of interleukin (IL)-1, IL-4, and IL-6 inflammatory cytokines were measured. The levels of messenger ribonucleic acid expression of proinflammatory cytokines and chemokines were measured using reverse transcription polymerase chain reaction. Inhibition of mitogen-activated protein kinase activation, was analyzed on western blot. To measure the transcriptional activity (NF-κB inhibition by BV liposomes), western blots (p65, p-IκB, p50, and IκB) were also performed. Results: The weight of lymph nodes, serum IgE concentrations, morphological changes in the skins from the backs of the mice, and mast cell numbers in inflamed tissues were noticeably lower in the BV liposome treatment group compared with the BV treatment group. The concentrations of pro-inflammatory cytokines (IL-1, IL-4, IL-6) and chemokines (TSLP, CCL22) were also reduced. Activation of mitogen-activated protein kinase (p-ERK and p-p38), and transcriptional activity (p65, p-IκB, p50, and IκB) was strongly suppressed in the BV liposome group. Conclusion: BV liposomes may have a better therapeutic effect than BV for the treatment of AD.

Systemic Review on Complementary and Alternative Medicine for Endometriosis (자궁내막증의 보완대체의학적 치료에 관한 연구)

  • Kwon, Ji-Myung;Park, Young-Sun;Kim, Dong-Chul
    • The Journal of Korean Obstetrics and Gynecology
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    • v.22 no.4
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    • pp.83-92
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    • 2009
  • Purpose: The aim of this study was to review systemically journals on the studies for complementary and alternative medicine in the treatment of endometriosis. Methods: Through medical websites, foreign clinical literatures about complementary and alternative medicines of endometriosis were searched. The cite used was http://www.Pubmed.gov. And then they were divided into three groups. In vitro, in vivo, clinical studies. Results: 1. We researched 2 papers about in vitro. Both were used extract of herbal mixture. And they used CCL5, SE-1, COUP-TF, 17-$\beta$-HSD1, 17-$\beta$-HSD2 which were not commonly used in Korea. 2. We researched 8 papers about in vivo. Most of them used blood-activating stasis-dispelling medicine, just few used tonic medicine. And they used acupuncture which were not used in Korea. Most of Korean paper also used blood-activating stasis-dispelling medicine and rarely used tonic medicine. 3. We researched 19 papers about clinical studies. They had much more cases(average=60) than Korean paper. They were also used western medicine randomized sham-controlled trial. Conclusion: Afterward we need to study for comparing western medicine and herb medicine. And we concern about acupuncture therapy.

Transcriptome Analysis of the Striatum of Electroacupuncture-treated Naïve and Ischemic Stroke Mice

  • Hong Ju Lee;Hwa Kyoung Shin;Ji-Hwan Kim;Byung Tae Choi
    • Journal of Pharmacopuncture
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    • v.27 no.2
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    • pp.162-171
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    • 2024
  • Objectives: Electroacupuncture (EA) has been demonstrated to aid stroke recovery. However, few investigations have focused on identifying the potent molecular targets of EA by comparing EA stimulation between naïve and disease models. Therefore, this study was undertaken to identify the potent molecular therapeutic mechanisms underlying EA stimulation in ischemic stroke through a comparison of mRNA sequencing data obtained from EA-treated naïve control and ischemic stroke mouse models. Methods: Using both naïve control and middle cerebral artery occlusion (MCAO) mouse models, EA stimulation was administered at two acupoints, Baihui (GV20) and Dazhui (GV14), at a frequency of 2 Hz. Comprehensive assessments were conducted, including behavioral evaluations, RNA sequencing to identify differentially expressed genes (DEGs), functional enrichment analysis, protein-protein interaction (PPI) network analysis, and quantitative real-time PCR. Results: EA stimulation ameliorated the ischemic insult-induced motor dysfunction in mice with ischemic stroke. Comparative analysis between control vs. MCAO, control vs. control + EA, and MCAO vs. MCAO + EA revealed 4,407, 101, and 82 DEGs, respectively. Of these, 30, 7, and 1 were common across the respective groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed upregulated DEGs associated with the regulation of inflammatory immune response in the MCAO vs. MCAO + EA comparison. Conversely, downregulated DEGs in the control vs. control + EA comparison were linked to neuronal development. PPI analysis revealed major clustering related to the regulation of cytokines, such as Cxcl9, Pcp2, Ccl11, and Cxcl13, in the common DEGs of MCAO vs. MCAO + EA, with Esp8l1 identified as the only common downregulated DEG in both EA-treated naïve and ischemic models. Conclusion: These findings underscore the diverse potent mechanisms of EA stimulation between naïve and ischemic stroke mice, albeit with few overlaps. However, the potent mechanisms underlying EA treatment in ischemic stroke models were associated with the regulation of inflammatory processes involving cytokines.

Beach Resort Formation and Development Processes by Fabric Construction in an Island Environment (구조물 축조에 의한 도서지역 해수욕장의 발달과정에 관한 연구 -완도군 보길면 지역을 사례로-)

  • 박의준;황철수
    • Journal of the Korean Geographical Society
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    • v.36 no.4
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    • pp.474-482
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    • 2001
  • The purpose of this study is to investigate the formation and development processes of beach resort by fabric construction in a island environment. The results are as follows. (1) The research area(Tong-ri beach, Bokil-myon, Chollanam-do)has been transformed to belch by sedimentary environmental change since latter half of 1800's. (2) The mean slope of beach face is 0.96°, and the difference of attitude between beach and mud flat face is 75cm. (3) The mean particle size of beach surface sediment is 3.53$\Phi$. This value is very finer than that of any other beach in Korea peninsula. But its value is coarser than that of mud flat surface sediment. (4) The particle size distribution of core sediment is become changed to fine particle in 70cm depth. This value is corresponded to difference of altitude between beach face and mud flat face. (5) The analysis of aerial photographs after 1970 indicates that sedimentation process was not brisked since 1970's. Consequently, the research ares has been developed by sedimentary environmental change for sea-level rise effect and wave height energy rise effect.

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The Complexes of Iodine with Ortho-Substituted Anilines in Carbon Tetrachloride (오르토 치환 아닐린과 요오드 사이의 착물에 관한 연구)

  • Bu Yong Lee;Sang Up Choi
    • Journal of the Korean Chemical Society
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    • v.15 no.6
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    • pp.312-317
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    • 1971
  • The interactions of aniline, o-toluidine, o-ethylaniline and o-chloroaniline with iodine in carbon tetrachloride solution have been examined through spectrophotometric measurements. The results indicate that both aniline and the o-substituted anilines examined form one-to-one complexes with I2in solution. The formation constants of the complexes measured at room temperature are 12.8, 9.31, 3.15 and 0.576 l $mole^{-1}$, respectively. Comparison of these results with previous experimental results indicates that the relative stabilities of the $I_2$-amine complexes decrease in the following order: $C_6H_5N(C_2H_5)_2 >C_6H_5N(CH_3)_2 >C_6H_5NH_2 >o-CH_3C_6H_4NH_2 >o-C_2H_5C_6H_4NH_2 >o-ClC_6H_4NH_2$. This may support the conclusion that the relative stabilities of these complexes are explained by the inductive effect and steric hindrance of the substituents.

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Antioxidative and Hepatoprotective Effect of Compounds Isolated from Galla Rhois(Rhus javanica Linne) (오배자 성분의 항산화 및 간보호 효과)

  • Cha, Bae-Cheon;Lee, Sung-Bae;Rhim, Tae-Jin;Lee, Kwang-Hoe
    • Korean Journal of Medicinal Crop Science
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    • v.8 no.2
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    • pp.157-164
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    • 2000
  • The major components were isolated from the n-hexane, EtOAc and BuOH extract of Galla Rhois(Rhus Javanica Linne). Their structures were characterized as syringic acid, gallic acid methylester, protocatechuic acid, gallic acid and 1, 2, 3, 4, $6-penta-O-galloyl-{\beta}-D-glucose$. This study was carried out to investigate the biological activities of isolated compounds. Five compounds were tested for hepatoprotective effects on CCl4-induced cytotoxicity in primary cultured rat hepatocytes and antioxidative effect on Ferric-Thiocyanate method and TBA method. As a result, isolated five compounds showed stronger antioxidative activity than tocopherol, and the antioxidative activity of gallic acid methylester, protocatechuic acid and syringic acid were similar to that of BHA on Ferric-Thiocyanate method. Specially 1, 2, 3, 4, $6-penta-O-galloyl-{\beta}-D-glucose$ showed stronger effect of lipid-peroxidation inhibition than BHA. Gallic acid appeared stronger inhibitory effect of malondialdehyde on TBA method. Hepatoprotective effect of 1, 2, 3, 4, $6-penta-O-galloyl -{\beta}-D-glucose$ was similar or even higher than that of glycyrrhizin on primary cultured rat hepatocyte cytotoxicity.

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The Study of Free Radical Scavenging Effect of Lycii Fructus by Liver Injury of Rats (백서 간손상에 의한 구기자의 유리자유기 소거능에 관한 연구)

  • Yoon Sang Ju;Jung Sun Yeong;Kim Young Mi;Ha Ki Tae;Kim Cheorl Ho;Kim Dong Wook;Kim June Ki;Choi Dall Yeong
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.17 no.1
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    • pp.91-100
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    • 2003
  • In the present study, we investigated the protective effect of the Lycii Fructus water extracts (LFE) against CCl4-induced hepatotoxicity and the mechanism underlying these protective effects in the rats. The pretreatment of LFE has shown to possess a significant protective effect by lowering the serum alanine and aspartate aminoteansferase (AST and ALT) and alkaline phosphatase (ALP). This hepatoprotective action was confirmed by histological observation, In addition, the pretreatment of LFE prevented the elevation of hepatic malondialdehyde (MDA) formation and the depletion of reduced glutathione (GSH) content and catalase activity in the liver of CC1₄-injected rats. The LFE also displayed hydroxide radical scavenging activity in a dose-dependent manner (IC50 = 83.6 μg/ml), as assayed by electron spin resonance (ESR) spin-trapping technique. Moreover, the expression of cytochrome P450 2E1 (CYP2E1) mRNA, as measured by reverse transcriptase-polymerase chain reaction (RT-PCR), was significantly decreased in the liver of LFE-pretreated rats when compared with that in the liver of control group. Based on these results, it was suggested that the hepatoprotective effects of the LFE may be related to antioxidant effects and regulation of CYP2E1 gene expression.