• 제목/요약/키워드: dose-response model

검색결과 303건 처리시간 0.036초

Cyclopiazonic acid 및 aflatoxin B1이 토끼의 혈소판 응집 및 ATP 방출에 미치는 영향 (Effects of cyclopiazonic acid and aflatoxin B1 on rabbit platelet aggregation and ATP release)

  • 홍충만;조명행
    • 대한수의학회지
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    • 제36권4호
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    • pp.887-894
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    • 1996
  • Cyclopiazonic acid(CPA) known as stimulating the release of intracellular calcium, aflatoxin $B_1(AFB_1)$ causing gastrointestinal hemorrhage frequently were used as model toxic mycotoxins in these studies. First of all, the effects of various mycotoxins on the platelet aggregation response were determined. The effects of mycotoxins on the ATP release from platelet by aggregating factors were investigated. The results and conclusions obtained from these studies are : 1) CPA promoted ADP, collagen, thrombin, A.A. and PAF-induced rabbit platelet aggregation. $AFB_1$ inhibited collagen, A.A. and PAF-induced rabbit platelet aggregation only. 2) CPA increased both aggregation and disaggregation time, whereas $AFB_1$ decreased in a dose dependent manner. 3) CPA increased ADP, thrombin, A.A. and PAF-induced ATP release. $AFB_1$ increased A.A.-induced ATP release and decreased PAF-induced release in a dose dependent manner. In conclusion, CPA promoted platelet aggregation by the increase of ATP. Antiaggregating effects of AFB1 may be due to decreases of ATP. These data provide the basis for the future study of roles of ATP release in platelet aggregation.

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수직방향 전신 충격진동의 불편함 평가를 위한 주파수가중곡선 개발 (Development of Frequency Weighting Shape for Evaluation of Discomfort due to Vertical Whole-body Shock Vibration)

  • 안세진;정의봉
    • 한국소음진동공학회논문집
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    • 제16권6호
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    • pp.658-664
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    • 2006
  • Shock vibrations are usually experienced in vehicles excited by impulsive input, such as bumps. The frequency weighting functions of the current standards in ISO 2631 and BS 6841 are to help objectively predict the amount of discomfort of stationary vibration. This experimental study was designed to develop frequency weighting shape for shock vibration having various fundamental frequencies from 0.5 to 16Hz. The specks were produced from the response of single. degree-of-freedom model to a half-sine force input. Fifteen subjects used the magnitude estimation method to judge the discomfort of vertical shock vibration generated on the rigid seat mounted on the simulator. The magnitudes of the shocks, expressed in terms of both peak-to-peak value and un-weighted vibration dose values (VDVs) , were correlated with magnitude estimates of the discomfort. The frequency weighting shapes from the correlation were developed and investigated having nonlinearity due to the magnitude of the shock.

솔잎 부탄올 분획의 예쁜꼬마선충 내의 항산화 효과 (Antioxidant Activities of n-Butanol Fraction of Pinus densiflora Siebold & Zucc. Needle in Caenorhabditis elegans.)

  • 김준형;김나영;권강무;황인현;김대근
    • 생약학회지
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    • 제52권2호
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    • pp.105-111
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    • 2021
  • To investigate the antioxidant activities of Pinus densiflora needle (Pinaceae), which is widely used as a traditional medicine in Korea, Caenorhabditis elegans model system was used. The n-butanol fraction of P. densiflora needle methanol extract showed the most potent DPPH radical scavenging and superoxide quenching activities in a dose-dependent manner. The n-butanol fraction was measured for the activities of superoxide dismutase (SOD), catalase, and oxidative stress tolerance by using C. elegans with reactive oxygen species (ROS) level. In addition, to see that the regulation of the stress response gene is responsible for the increased stress tolerance of C. elegans treated by the butanol extract, SOD-3 expression was measured using a transgenic strain. As a result, the P. densiflora needle n-butanol fraction increased SOD and catalase activities, and decreased ROS accumulation, dose-dependently. Furthermore, the n-butanol fraction-treated CF1553 worm showed higher SOD-3::GFP intensity than the control.

돼지감자꽃의 예쁜꼬마선충 내의 항산화 효과 (Antioxidant Activity of Helianthus tuberosus L. Flower in Caenorhabditis elegans)

  • 김준형;이예빈;한선여;김수진;황인현;김대근
    • 생약학회지
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    • 제50권2호
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    • pp.96-101
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    • 2019
  • Methanol extract of Helianthus tuberosus L. (Compositae) flower was investigated to research the anti-oxidative activity by using a Caenorhabditis elegans model system. Ethyl acetate soluble fraction of the methanol extract showed the most potent DPPH radical scavenging activity. The ethyl acetate fraction was measured on its activities of superoxide dismutase (SOD), catalase, and oxidative stress tolerance with reactive oxygen species (ROS) level in C. elegans. Furthermore, in order to verify if regulation of stress-response gene is responsible for the increased stress tolerance of C. elegans which treated by the ethyl acetate fraction, we checked SOD-3 expression using a transgenic strain. Consequently, the ethyl acetate fraction of H. tuberosus flower increased the catalase and SOD activities in a dose-dependent manner in C. elegans, reduced ROS accumulation dose-dependently. Besides, the ethyl acetate fraction-treated CF1553 worms showed higher SOD-3::GFP intensity than the control group.

Interaction of HIV-1 Core p24 Antigen with Human Monocytic Cell Line THP1 Results in TNF-${\alpha}$ Dependent Secretion of Matrix Metalloproteinase-9

  • Sung, Ji-Hye;Yoo, Seung-Hee;Park, Hae-Kyung;Chong, Young-Hae
    • 대한미생물학회지
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    • 제35권1호
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    • pp.9-18
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    • 2000
  • Immunological mechanisms involving the release of inflammatory factors by HIV-1 infected microglia in the brain have been implicated in the pathogenesis of HIV dementia (HIVD). Since the regulation of matrix metalloproteinases (MMPs) activity can be influenced by variety of inflammatory mediators, this study was undertaken to look for a correlation between the MMP-9 release and the production of TNF-${\alpha}$ in response to HIV-1 p24 in the human monocyte cell line THP-1 as a model for microglia. First, it was shown that HIV-l core p24 antigen induced THP-1 to secrete MMP-9 in a dose response manner while it elicited a little effect on MMP-2 release in human astroglial cell line T98G. Next, it was found that p24 induced THP-1 to secrete TNF-${\alpha}$ without prior differentiation into macrophages by phorbol myristate acetate (PMA) treatment. Furthermore, anti-TNF-${\alpha}$ neutralizing antibodies significantly blocked p24-induced MMP-9 release in a dose dependent manner. Our data indicate that p24 antigen induces monocytic MMP-9 release by triggering up-regulation of TNF-${\alpha}$ secretion.

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Acanthopanax koreanum Nakai modulates the immune response by inhibiting TLR 4-dependent cytokine production in rat model of endotoxic shock

  • Jung, Myung-Gi;Do, Gyeong-Min;Shin, Jae-Ho;Ham, Young Min;Park, Soo-Yeong;Kwon, Oran
    • Nutrition Research and Practice
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    • 제7권6호
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    • pp.460-465
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    • 2013
  • The hepatoprotective activity of Acanthopanax koreanum Nakai extract (AE) was investigated against D-Galactosamine/Lipopolysaccharide (D-GalN/LPS)-induced liver failure rats compared with that of acanthoic acid (AA) isolated from AE. Although D-GalN/LPS (250 mg/kg body weight/$10{\mu}g/kg$ body weight, i.p.) induced hepatic damage, pretreatments with AE (1 and 3% AE/g day) and AA (0.037% AA, equivalent to 3% AE/g day) alleviated the hepatic damage. This effect was the result of a significant decrease in the activity of alanine transaminase. Concomitantly, both the nitric oxide and IL-6 levels in the plasma were significantly decreased by high-dose AE (AE3) treatment compared to the GalN/LPS control (AE0). This response resulted from the regulation of pro-inflammatory signaling via a decrease in TLR4 and CD14 mRNA levels in the liver. While a high degree of necrosis and hemorrhage were observed in the AE0, pretreatment with AE3 and AA reduced the extent of hepatocyte degeneration, necrosis, hemorrhage and inflammatory cell infiltrates compared to the AE0. In conclusion, these results suggest that especially high-dose AE are capable of alleviating D-GalN/LPS-induced hepatic injury by decreasing hepatic toxicity, thereby mitigating the TLR 4-dependent cytokine release. The anti-inflammatory effect of AE could be contributing to that of AA and AE is better than AA.

Quality Prediction of Eggs Treated in Combination with Gamma Irradiation and Chitosan Coating Using Response Surface Methodology

  • Lee, Kyung-Heang;Jung, Samooel;Ham, Jun-Sang;Lee, Jun-Heon;Lee, Soo-Kee;Jo, Cheo-Run
    • Journal of Animal Science and Technology
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    • 제53권3호
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    • pp.253-259
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    • 2011
  • The aim of this work was to determine the method and predict the optimum conditions for egg quality stored for 7 days when combination treatments of irradiation and chitosan coating were applied using response surface methodology (RSM). A central composite design was chosen for the RSM in this study and the factors were irradiation dose (0~2 kGy) and concentration of chitosan coating material (0~2%). Performance of the irradiation and chitosan coating were evaluated by analyzing the egg quality and functional property factors. The predicted maximum level of Haugh units and foaming ability calculated by a developed model were 74.19 at 0 kGy of irradiation with coating by 0.96% chitosan solution and 50.83 mm at 2.0 kGy with 1.01%, respectively. The predicted minimum value of foam stability and 2-thiobarbituric acid reactive substances (TBARS) value were 2.97 mm at 0.39 kGy with 0.21% and 0.54 mg malonaldehyde/kg egg yolk at 0 kGy with 0.90% of chitosan solution, respectively. Results clearly showed that gamma irradiation negatively affected the Haugh unit and TBARS but positively affected the foaming capacity. The estimated value from the developed model by RSM was verified by no statistical difference with observed value. Therefore, RSM can be a good tool for optimization and prediction of egg quality when 2 or more treatments are combined. However, one should decide the target quality first to achieve a successful implementation of this technology.

Papaverine Exerts Neuroprotective Effect by Inhibiting NLRP3 Inflammasome Activation in an MPTP-Induced Microglial Priming Mouse Model Challenged with LPS

  • Leem, Yea-Hyun;Park, Jin-Sun;Park, Jung-Eun;Kim, Do-Yeon;Kim, Hee-Sun
    • Biomolecules & Therapeutics
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    • 제29권3호
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    • pp.295-302
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    • 2021
  • Microglial priming is the process of microglial proliferation and activation in response to neurodegeneration and abnormal protein accumulation. Priming makes microglia susceptible to secondary inflammatory stimuli and causes exaggerated inflammatory responses. In the present study, we established a microglial priming model in mice by administering a single injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 20 mg/kg). MPTP induced microglial activation without dopaminergic degeneration; however, subsequent treatment with a sub-toxic dose of lipopolysaccharides (LPS) induced an amplified inflammatory response and caused nigrostriatal dopaminergic degeneration. These pathological and inflammatory changes, including microglial activation and dopaminergic cell loss in the substantia nigra (SN) area were reversed by papaverine (PAP) administration. In addition, MPTP/LPS enhanced interleukin-1β (IL-1β) expression and processing via nod-like receptor protein 3 (NLRP3) inflammasome activation in the SN region of mice. However, PAP treatment suppressed inflammasome activation and subsequent IL-1β maturation. Moreover, PAP inhibited nuclear factor-κB (NF-κB) and enhanced cAMP-response element binding protein (CREB) activity in the SN of MPTP/LPS mice. These results suggest that PAP inhibits the activation of NLRP3 inflammasome by modulating NF-κB and CREB signaling pathways, which results in reduced microglial activation and neuronal cell death. Thus, PAP may be a potential candidate for the treatment of Parkinsons's disease, which is aggravated by systemic inflammation.

Application of Apoptogenic Pretreatment to Enhance Anti-tumor Immunity of Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)-secreting CT26 Tumor Cells

  • Jun, Do-Youn;Jaffee, Elizabeth M;Kim, Young-Ho
    • IMMUNE NETWORK
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    • 제5권2호
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    • pp.110-116
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    • 2005
  • Background: As an attempt to develop a strategy to improve the protective immune response to GM-CSF-secreting CT26 (GM-CSF/CT26) tumor vaccine, we have investigated whether the apoptogenic treatment of GM-CSF/CT26 prior to vaccination enhances the induction of anti-tumor immune response in mouse model. Methods: A carcinogeninduced mouse colorectal tumor, CT26 was transfected with GM-CSF gene using a retroviral vector to generate GM-CSF-secreting CT26 (CT26/GM-CSF). The CT26/GM-CSF was treated with ${\gamma}$-irradiation or mitomycin C to induce apoptosis and vaccinated into BALB/c mice. After 7 days, the mice were injected with a lethal dose of challenge live CT26 cells to examine the protective effect of tumor vaccination in vivo. Results: Although both apoptotic and necrotic CT26/GM-CSF vaccines were able to enhance anti-tumor immune response, apoptotic CT26/GM-CSF induced by pretreatment with ${\gamma}$-irradiation (50,000 rads) was the most potent in generating the anti-tumor immunity, and thus 100% of mice vaccinated with the apoptotic cells remained tumor free for more than 60 days after tumor challenge. Conclusion: Apoptogenic pretreatment of GM-CSF-secreting CT26 tumor vaccine by ${\gamma}$-irradiation (50,000 rads) resulted in a significant enhancement in inducing the protective anti-tumor immunity. A rapid induction of apoptosis of CT26/GM-CSF tumor vaccine at the vaccine site might be critical for the enhancement in anti-tumor immune response to tumor vaccine.

Predictors of Outcome in Patients with Advanced Nonseminomatous Germ Cell Testicular Tumors

  • Yetisyigit, Tarkan;Babacan, Nalan;Urun, Yuksel;Seber, Erdogan Selcuk;Cihan, Sener;Arpaci, Erkan;Yildirim, Nuriye;Aksoy, Sercan;Budakoglu, Burcin;Zengin, Nurullah;Oksuzoglu, Berna;Yalcin, Banu Cicek;Alkis, Necati
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권2호
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    • pp.831-835
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    • 2014
  • Background: Predictor factors determining complete response to treatment are still not clearly defined. We aimed to evaluate clinicopathological features, risk factors, treatment responses, and survival analysis of patient with advanced nonseminomatous GCTs (NSGCTs). Materials and Methods: Between November 1999 and September 2011, 140 patients with stage II and III NSGCTs were referred to our institutions and 125 patients with complete clinical data were included in this retrospective study. Four cycles of BEP regimen were applied as a first-line treatment. Salvage chemotherapy and/or high-dose chemotherapy (HDCT) with autologous stem cell transplantation were given in patients who progressed after BEP chemotherapy. Post-chemotherapy surgery was performed in selected patients with incomplete radiographic response and normal tumor markers. Results: The median age was 28 years. For the good, intermediate and poor risk groups, compete response rates (CRR) were, 84.6%, 67.9% and 59.4%, respectively. Extragonadal tumors, stage 3 disease, intermediate and poor risk factors, rete testis invasion were associated with worse outcomes. There were 32 patients (25.6%) with non-CR who were treated with salvage treatment. Thirty-one patients died from GCTs and 94% of them had stage III disease. Conclusions: Even though response rates are high, some patients with GCTs still need salvage treatment and cure cannot be achieved. Non-complete response to platinium-based first-line treatment is a negative prognostic factor. Our study confirmed the need for a prognostic and predictive model and more effective salvage approaches.