• Title/Summary/Keyword: Multiple-dose

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Paraquat Induces Apoptosis through a Mitochondria-Dependent Pathway in RAW264.7 Cells

  • Jang, Yeo Jin;Won, Jong Hoon;Back, Moon Jung;Fu, Zhicheng;Jang, Ji Min;Ha, Hae Chan;Hong, SeungBeom;Chang, Minsun;Kim, Dae Kyong
    • Biomolecules & Therapeutics
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    • v.23 no.5
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    • pp.407-413
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    • 2015
  • Paraquat dichloride (N,N-dimethyl-4-4'-bipiridinium, PQ) is an extremely toxic chemical that is widely used in herbicides. PQ generates reactive oxygen species (ROS) and causes multiple organ failure. In particular, PQ has been reported to be an immunotoxic agrochemical compound. PQ was shown to decrease the number of macrophages in rats and suppress monocyte phagocytic activity in mice. However, the effect of PQ on macrophage cell viability remains unclear. In this study, we evaluated the cytotoxic effect of PQ on the mouse macrophage cell line, RAW264.7 and its possible mechanism of action. RAW264.7 cells were treated with PQ (0, 75, and $150{\mu}M$), and cellular apoptosis, mitochondrial membrane potential (MMP), and intracellular ROS levels were determined. Morphological changes to the cell nucleus and cellular apoptosis were also evaluated by DAPI and Annexin V staining, respectively. In this study, PQ induced apoptotic cell death by dose-dependently decreasing MMP. Additionally, PQ increased the cleaved form of caspase-3, an apoptotic marker. In conclusion, PQ induces apoptosis in RAW264.7 cells through a ROS-mediated mitochondrial pathway. Thus, our study improves our knowledge of PQ-induced toxicity, and may give us a greater understanding of how PQ affects the immune system.

Britanin Suppresses IgE/Ag-Induced Mast Cell Activation by Inhibiting the Syk Pathway

  • Lu, Yue;Li, Xian;Park, Young Na;Kwon, Okyun;Piao, Donggen;Chang, Young-Chae;Kim, Cheorl-Ho;Lee, Eunkyung;Son, Jong Keun;Chang, Hyeun Wook
    • Biomolecules & Therapeutics
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    • v.22 no.3
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    • pp.193-199
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    • 2014
  • The aim of this study was to determine whether britanin, isolated from the flowers of Inula japonica (Inulae Flos), modulates the generation of allergic inflammatory mediators in activated mast cells. To understand the biological activity of britanin, the authors investigated its effects on the generation of prostaglandin $D_2$ ($PGD_2$), leukotriene $C_4$ ($LTC_4$), and degranulation in IgE/Ag-induced bone marrow-derived mast cells (BMMCs). Britanin dose dependently inhibited degranulation and the generations of $PGD_2$ and $LTC_4$ in BMMCs. Biochemical analyses of IgE/Ag-mediated signaling pathways demonstrated that britanin suppressed the phosphorylation of Syk kinase and multiple downstream signaling processes, including phospholipase $C{\gamma}1$ ($PLC{\gamma}1$)-mediated calcium influx, the activation of mitogen-activated protein kinases (MAPKs; extracellular signal-regulated kinase 1/2, c-Jun $NH_2$-terminal kinase and p38), and the nuclear factor-${\kappa}B$ ($NF-{\kappa}B$) pathway. Taken together, the findings of this study suggest britanin suppresses degranulation and eicosanoid generation by inhibiting the Syk-dependent pathway and britanin might be useful for the treatment of allergic inflammatory diseases.

Pathological observation on the piglets experimentally infected with Aujeszky′s disease virus isolated in Korea (국내 분리 오제스키병 바이러스 접종자돈의 병리학적 관찰)

  • Park, Nam-Yong;Chung, Chi-Young;Kim, JIn-Ho;Yoon, Jin-Gyu;Park, Young-Seok
    • Korean Journal of Veterinary Pathology
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    • v.2 no.2
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    • pp.117-125
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    • 1998
  • Pathological studies were performed on the five piglets experimentally infected with Aujeszky's disease virus(pseudorabies), NYJ isolate, isolated from the naturally infected pigs in Korea: two piglets were inoculated intramuscularly, two piglets intranasally, and one piglet subcutaneously at the dose of 1$m\ell$ per animal with the 105.5 $TCID_50$/0.1ml titer. Clinical signs included dyspnea, high fever(>$41^{\circ}C$), anorexia, vomiting, diarrhea or constipation, ataxia, circling movement, posterior paralysis, intermittent convulsion, and coma followed by death although some variations by age and inoculated routes were observed. Gross features included multiple necrotic foci in the liver, congestion and hemorrhage in the lymph nodes and spleen, petechial hemorrhage in the kidney, hemorrhagic pneumonia, marked meningeal congestion, severe sub meningeal hemorrhage in the spinal cord, excessive cerebrospinal fluid retention, and muscular necrosis at the inoculated area. Microscopically, non suppurative meningoencephalitis with gliosis and perivascular cuffing in CNS, ganglioneuritis, necrohemorrhagic splenitis, necrotic hepatitis, tonsillitis and rhinitis, hemorrhagic or interstitial pneumonia, and non-suppurative myositis in the injected area were observed. Eosinophilic intranuclear inclusion bodies were found in a variety of tissues the including the liver, kidney, adrenal gland, spleen, lymph nodes, tonsil, and lung. Ultrastructurally, virus particles were confirmed in nucleus and cytoplasms of pneumocytes around the necrotic areas.

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Immunomodulatory Effects of a Methanol Extract from Opuntia ficus indica on Murine Splenocytes

  • Ahn, Gin-Nae;Kim, Jin-Hee;Park, Eun-Jin;Lim, Yoon-Kyu;Jeon, You-Jin;Jee, Young-Heun
    • Food Science and Biotechnology
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    • v.18 no.6
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    • pp.1316-1321
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    • 2009
  • Multiple beneficial properties of Opuntia ficus indica (OPF) are well established. In the present study, we have investigated the immunological role of OPF extract (OPFE) on murine splenocytes. OPFE dose- and time-dependently enhanced the proliferation of splenocytes without cytotoxicity. Our results also showed that the number of $CD4^+$ helper T cells and CD45R/$B220^+$ pan B cells increased markedly, but not $CD8^+$ cytotoxic T cells or $CD11b^+$ granulocytes/macrophages. In addition, OPFE significantly decreased the production levels of T helper (Th) 1 type cytokines, interferon (IFN)-$\gamma$, and tumor necrosis factor (TNF)-$\alpha$, although had no significantly differences in those of interleukin (IL)-4, a Th2 type cytokine in concanavalin A (Con A)-stimulated blastogenic cells. Furthermore, OPFE alone strongly increased IL-4 production and decreased TNF-$\alpha$ production even in the absence of Con A. On the basis of these results, this study suggests that OPFE enhances immunity by regulating the pro- and anti-inflammatory response, indicating that this extract exerts a marked immunomodulatory effect, confirming its usefulness as therapy for immune-related diseases.

Effect of Mori Follium Extract on the Melanogenesis and Skin Fibril Matrix (상엽(桑葉) 추출물의 미백활성 및 피부섬유구조 형성에 미치는 효과)

  • Kwon, O Jun
    • The Korea Journal of Herbology
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    • v.31 no.5
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    • pp.41-46
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    • 2016
  • Objectives : The Skin is composed of multiple layers, including the epidermis, dermis, and hypodermis. It provides a vital barrier structure that protects vertebrates from external environmental antigens, solvents, ultraviolet light, microorganisms, toxins, and weather conditions. Although several biological effects of Mori Follium have been reported, beneficial effects of Mori Follium in skin health remain unclear. In this study, we prepared water extract of Mori Follium (MLE) and evaluated the effects on melanin accumulation and expression levels of skin fibril-related proteins.Methods : The cytotoxicities of MLE in B16F10 melanoma and human skin fibroblasts (HSF) were examined by MTT assay. Inhibitory effect of MLE on the α-MSH- and IBMX-induced melanosis in B16F10 melanoma was examined. The expression levels of fibronectin, collagen 1α2, and CCN2 in MLE-treated HSF were analyzed by reverse transcription-polymer chain reaction (RT-PCR) and western blotting.Results : The MLE treatment for 24 h did not affect to the B16F10 and HSF at concentrations of 1, 10, 50, 100, 200, 400 and 800 ㎍/ml. The MLE treatment for 72 h significantly and dose dependently suppressed melanin accumulation in B16F10 melanoma. In addition, the MLE treatment up-regulated expression levels of skin fibril-related genes such as fibronectin, collagen 1α2, and CCN2 in HSF. Our western blot analysis revealed MLE-induced up-regulation of skin fibril-related genes required the activation of CCN2 protein.Conclusions : In conclusion, these findings suggest that the MLE could be used in development of cosmetic natural material of maintaining healthy skin.

HIMALAYAN MEDICINAL RESOURCES: PRESENT AND FUTURE. A CASE STUDY: ANTIDIABETIC ACTIVITY OF SHILAJIT

  • Basnet, Purusotam
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2001.11a
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    • pp.20-33
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    • 2001
  • A major portion of drugs used in Ayurvedic system of medicine which has been practiced since the early human civilization in Indian subcontinent were of plant origin. It should be noted that 70% of the population in this region depends on Ayurveda for their medical treatment and 60% of the drug resources are obtained from the Himalayan region. Therefore, Nepal becomes a potential source of plant drug resource since it occupies a major portion of the Himalaya. In the present paper, in general a current status of medicinal plant resources of Himalayan region especially Nepal will be discussed. In addition to this, a typical example of antidiabetic activity of Shilajit will be taken for the discussion. Shilajit is one of the crucial elements in several formulations including those of Rasayana, a therapy in Ayurveda, which has been practiced in the prevention of ageing and mental disorder. Although, Shilaiit is widely used for the treatment of diabetes, no satisfactory scientific reports are available up to now. The crude Shilajit in the market is a dark brown or black rock-like substance collected from the Himalayan region with a strong smell of cow's stale urine. In our studies, Shilajit (collected in the central Himalayan region) prevented the diabetes in nonobese diabetic (NOD) mice model. Shilajit also prevented the diabetes in the rats against the action of multiple low-dose (10 ㎎/㎏, i.v., 5 times) of streptozotocin. On the other hand, Shilajit did not show antioxidative activity. The preventive action of Shilajit on diabetes is mainly focused on the Th1 and Th2 cell activities, since Th2 cells activity was found to be significantly upregulated. Shilajit, however, showed a mild action in controlling the blood sugar level in young, old, and mild diabetic rats, but not in the severe diabetic rats. It also stimulated the nitric oxide production in macrophages. Based on these evidences, the antidiabetic activities of Shilajit appear to be immunomodulative probably by protecting or strengthening insulin-producing b-cells In the pancreas. further systematic research on constituents of Shilajit and its quality evaluation is necessary to enable the use of natural medicines in the treatment of diabetes.

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Flower MeOH Extract of Panax Notoginseng Attenuates the Production of Nitric Oxide and Pro-inflammatory Cytokines in LPS-stimulated RA W264.7 Cells (삼칠화(三七花)의 대식세포로부터 LPS에 의해 유도되는 nitric oxide와 전염중성 사이토카인의 생성 억제효과)

  • Joo, Ye-Jin;Jung, Hye-Mi;Seo, Un-Kyo
    • The Journal of Korean Medicine
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    • v.30 no.1
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    • pp.150-162
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    • 2009
  • Objectives: Inflammatory mediators, such as nitric oxide (NO), prostaglandin E2 ($PGE_2$) and pro-inflammatory cytokines, TNF-${\alpha}$ and IL-$1{\beta}$ playa critical role in inflammatory immune response. Therefore, intervention of inflammatory mediator production promises therapeutic benefit for treatment of many chronic inflammatory diseases, such as allergic asthma, rheumatoid arthritis, multiple sclerosis, septic shock and neurodegenerative diseases. In this study, the pharmacological effects of the flower MeOH extract Panax notoginseng (Notoginseng Flos; NF) on inflammation were investigated to address potential therapeutic or toxic effects. Methods: RA W264.7 cells were treated with different concentrations of NF methanol (NF-M) extract in the presence or absence of LPS ($1{\mu}g/m{\ell}$). Results: NF-M extract significantly inhibited LPS-induced production of NO, $PGE_2$ and pro-inflammatory cytokines, TNF-${\alpha}$ and IL-$1{\beta}$ in a dose-dependent manner. In addition, NF-M extract suppressed mRNA expressions and protein levels of iNOS, COX-2 and pro-inflammatory cytokines in LPS-stimulated RA W264.7 cells. Conclusion: These results indicated that NF-M extract inhibits LPS-induced production of inflammatory mediators in macrophages and demonstrated that NF-M extract possesses anti-inflammatory properties in vitro.

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Design and Performance Analysis of Satellite Terminal Management Protocol in KMILSATCOM (군 위성통신체계 위성단말관리 프로토콜 설계 및 성능분석)

  • Lee, Jong-Seong;Choe, Hyeong-Seok;Hwang, In-Gwan
    • Journal of Satellite, Information and Communications
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    • v.2 no.1
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    • pp.14-20
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    • 2007
  • The Korean Military Satellite Communication System (KMILSATCOM) is composed of military payload of KOREASAT 5 and military satellite terminals. The military satellite terminals communicate with each other in satellite service area. The satellite terminal management system is developed for centralized management of satellite terminals and communications link. The satellite terminal management system dose not use terrestrial networks (i.e. Fiber optic, Microwave) for management because the KMILSATCOM is system for emergency (i.e. war time) and the satellite terminals has to move to operational area, so the management link must use satellite link. The management link is composed of 1 to N communication scheme for one manager and multiple terminals. This paper describes the satellite terminal management protocol architecture and the performance of the protocol of the KMILSATCOM system.

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Upgrade of Neutron Energy Spectrometer with Single Multilayer Bonner Sphere Using Onion-like Structure

  • Mizukoshi, Tomoaki;Watanabe, Kenichi;Yamazaki, Atsushi;Uritan, Akira;Iguchi, Tetsuo;Ogata, Tomohiro;Muramatsu, Takashi
    • Journal of Radiation Protection and Research
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    • v.41 no.3
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    • pp.185-190
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    • 2016
  • Background: In order to measure neutron energy spectra, the conventional Bonner Sphere Spectrometers (BSS) are widely used. In this spectrometer, several measurements with different size Bonner spheres are required. Operators should, therefore, place these spheres in several times to a measurement point where radiation dose might be relatively high. In order to reduce this effort, novel neutron energy spectrometer using an onion-like single Bonner sphere was proposed in our group. This Bonner sphere has multiple sensitive spherical shell layers in the single sphere. In this spectrometer, a band-shaped thermal neutron detection medium, which consists of a LiF-ZnS mixed powder scintillator sheet and a wavelength-shifting (WLS) fiber readout, was looped to each sphere at equal angular intervals. Amount of LiF neutron converter is reduced near polar region, where the band-shaped detectors are concentrated, in order to uniform the directional sensitivity. The LiF-ZnS mixed powder has an advantage of extremely high light yield. However, since it is opaque, scintillation photons cannot be collect uniformly. This type of detector shows no characteristic shape in the pulse height spectrum. Subsequently, it is difficult to set the pulse height discrimination level. This issue causes sensitivity fluctuation due to gain instability of photodetectors and/or electric modules. Materials and Methods: In order to solve this problem, we propose to replace the LiF-ZnS mixed powder into a flexible and Transparent RUbber SheeT type $LiCaAlF_6$ (TRUST LiCAF) scintillator. TRUST LiCAF scintillator can show a peak shape corresponding to neutron absorption events in the pulse height spectrum. Results and Discussion: We fabricated the prototype detector with five sensitive layers using TRUST LiCAF scintillator and conducted basic experiments to evaluate the directional uniformity of the sensitivity. Conclusion: The fabricated detector shows excellent directional uniformity of the neutron sensitivity.

Effect of Korean Red Ginseng extracts on drug-drug interactions

  • Kim, Se-Jin;Choi, Seungmok;Kim, Minsoo;Park, Changmin;Kim, Gyu-Lee;Lee, Si-On;Kang, Wonku;Rhee, Dong-Kwon
    • Journal of Ginseng Research
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    • v.42 no.3
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    • pp.370-378
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    • 2018
  • Background: Ginseng has been the subject of many experimental and clinical studies to uncover the diverse biological activities of its constituent compounds. It is a traditional medicine that has been used for its immunostimulatory, antithrombotic, antioxidative, anti-inflammatory, and anticancer effects. Ginseng may interact with concomitant medications and alter metabolism and/or drug transport, which may alter the known efficacy and safety of a drug; thus, the role of ginseng may be controversial when taken with other medications. Methods: We extensively assessed the effects of Korean Red Ginseng (KRG) in rats on the expression of enzymes responsible for drug metabolism [cytochrome p450 (CYP)] and transporters [multiple drug resistance (MDR) and organic anion transporter (OAT)] in vitro and on the pharmacokinetics of two probe drugs, midazolam and fexofenadine, after a 2-wk repeated administration of KRG at different doses. Results: The results showed that 30 mg/kg KRG significantly increased the expression level of CYP3A11 protein in the liver and 100 mg/kg KRG increased both the mRNA and protein expression of OAT1 in the kidney. Additionally, KRG significantly increased the mRNA and protein expression of OAT1, OAT3, and MDR1 in the liver. Although there were no significant changes in the metabolism of midazolam to its major metabolite, 1'-hydroxymidazolam, KRG significantly decreased the systemic exposure of fexofenadine in a dose-dependent manner. Conclusion: Because KRG is used as a health supplement, there is a risk of KRG overdose; thus, a clinical trial of high doses would be useful. The use of KRG in combination with P-glycoprotein substrate drugs should also be carefully monitored.