• Archives of Pharmacal Research
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• 제26권1호
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• pp.83-88
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• 2003

KR-984055 is a new oral cephalosporin antibiotic with activity against both gram-positive and gram-negative bacteria. Lipophilic ester-type prodrugs of KR-984055, i.e., KR-999001 and KR-999002, have been synthesized in an attempt to increase the oral bioavailability of this broad-spectrum antibiotic agent. In this study we determined the oral bioavailability of KR-984055 and its prodrugs in the rat, and evaluated the pharmacokinetic model that best describes the plasma concentration behavior following single intravenous (IV) and oral single dose. In addition, concentrations in plasma as well as biliary and urinary recovery of KR-984055 were determined. Also, protein binding of KR-984055 in plasma was examined in vitro. The degree of protein binding of KR-984055 was in the range of 92.09~94.77%. KR-984055 exhibited poor oral bioavailability (7.02$\pm$1.58%). The observed oral bioavailabilities of KR-984055 from KR-999001 and KR-999002 were 38.77$\pm$2.81 % and 39.81$\pm$5.25%, respectively. These data were calculated from the levels of free KR-984055 in plasma. Oral KR-999001 and KR-999002 were not recovered from plasma, suggesting that it was readily cleaved to free KR-984055. KR-999001 and KR-999002 appear to be an efficient oral prod rug of KR-984055 that deserved further clinical evaluation in human.

• 한국ITS학회 논문지
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• 제14권6호
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• pp.21-36
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• 2015

최근 활발히 개발되고 있는 자율주행차량은 현대사회의 다양한 교통문제를 해결하기 위한 근본적인 대안으로 주목 받고 있으며, 그 효과를 예측하기 위한 연구 또한 지속적으로 진행되어왔다. 하지만 기존연구는 주로 가상의 도로를 대상으로 하여 현 도로교통시스템에 가져올 다양한 편익에 대한 검토는 미비한 상태이다. 이에 본 연구는 자율주행차량 테스트베드 구축 예정구간인 경부고속도로 서울-신갈 기본구간을 대상으로, 자율주행차량 도입에 따른 속도 및 밀도 등 다양한 교통류의 변화를 분석하였다. 분석 결과, 교통량이 적은 서비스수준 A, B 상황에서는 자율주행차량 혼입이 교통류에 부정적인 영향을 미치는 것으로 나타났다. 반면, 교통량이 많아지는 서비스수준 C 이상의 상황에서는 자율주행차량 도입에 따라 평균속도가 증가하고 밀도가 감소하여 교통류에 긍정적인 영향을 미치는 것으로 분석되었다. 이에 따라, 자율주행차량 도입이 교통혼잡 등 다양한 교통문제를 효과적으로 해결할 수 있을 것이라 기대된다.

• 한국조사연구학회지:조사연구
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• 제1권2호
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• pp.59-87
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• 2000

기업체에서 변화 활동을 담당하는 변화 담당자 305명을 대상으로 이들의 자기관, 모험 수용성고 같은 성격특성이 조직이 추진하는 변화활동 및 담당업무에 대한 적응에 미치는 효과를 살펴보았다. 연구결과, 긍정적인 자기관과 모험 수용성이 높은 사람들은 조직이 추진하고 있는 변화활동관련 업무를 보다 적극적으로 수행하고 있었으며, 담당하는 변화관련 업무에 대한 적응도가 높은 것으로 나타났다. 또한 변화대응성은 긍정적인 자기관 및 모험 수영성과 업무에 대한 적응간을 매개하는 변수역할을 하는 것으로 나타났다. 본 연구결과는 변화담당자가 조직에서 추진하는 변화관련 업무를 원활하게 수행하기 위해서는 긍정적인 자기관과 모험 수용성을 보유하는 것이 필요하며, 조직에서 변화 담당자를 선발하고 이들을 교육할 때 이들의 자기관을 긍정적으로 변화시켜주고, 모험 수용성을 높여주는 것(또는 이런 성향이 높은 사람을 선발하는 것)이 바람직함을 시사한다. 또한 변화담당자들이 자신들이 담당하는 업무에 쉽게 적응하도록 하기 위해서는 이들의 변화대응성을 높이는 것이 필요함을 시사한다.

• 정보처리학회논문지:소프트웨어 및 데이터공학
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• 제3권5호
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• pp.169-178
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• 2014

본 논문에서는 상호 작용 중심 시스템의 품질을 확보하기 위하여 LTL 분산 명세를 활용하는 연구를 소개한다. 이러한 시스템의 품질확보를 위해서는 모듈 간의 상호 작용을 확인하여 기대하는 요구 사항을 달성하고 있는지를 검사해야 한다. 이 작업은 어렵고 노동 집약적이며 전문가를 필요로 한다. 따라서 본 논문에서는 이 검사에 도움을 주기 위한 방법을 제안한다. 먼저, 시스템의 기대하는 요구 사항은 각 모듈별로 분리해서 명세한다. 그리고 모듈 사이의 상호 작용은 다른 모듈이 수행하는 행위가 특정 모듈의 행위와 관련 있음을 의미한다. 여기서는 GR(1) 합성을 이용하여 명세를 만족하는 오토마타 모델이 생성되고 이것들은 소프트웨어 에이전트 기반의 시뮬레이터를 통해 모델의 행위를 확인하여 시스템이 요구 사항을 달성하고 있는지를 검사한다.

• BMB Reports
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• 제37권2호
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• pp.239-245
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• 2004

We have previously demonstrated that the redox reactant pyruvate prevents apoptosis in the oxidant model of bovine pulmonary artery endothelial cells (BPAEC), and that the anti-apoptotic mechanism of pyruvate is mediated in part via the mitochondrial matrix compartment. However, cytosolic mechanisms for the cytoprotective feature of pyruvate remain to be elucidated. This study investigated the pyruvate protection against endothelial cytotoxicity when the glycolysis inhibitor 2-deoxy-D-glucose (2DG) was applied to BPAEC. Millimolar 2DG blocked the cellular glucose uptake in a concentration- and time-dependent manner with >85% inhibition at $\geq$5 mM within 24 h. The addition of 2DG evoked BPAEC cytotoxicity with a substantial increase in lipid peroxidation and a marked decrease in intracellular total glutathione. Exogenous pyruvate partially prevented the 2DG-induced cell damage with increasing viability of BPAEC by 25-30%, and the total glutathione was also modestly increased. In contrast, 10 mM L-lactate, as a cytosolic reductant, had no effect on the cytotoxicity and lipid peroxidation that are evoked by 2DG. These results suggest that 2DG toxicity may be a consequence of the diminished potential of glutathione antioxidant, which was partially restored by exogenous pyruvate but not L-lactate. Therefore, pyruvate qualifies as a cytoprotective agent for strategies that attenuate the metabolic dysfunction of the endothelium, and cellular glucose oxidation is required for the functioning of the cytosolic glutathione/NADPH redox system.

• Journal of Ginseng Research
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• 제39권4호
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• pp.304-313
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• 2015

Background: Ginsenoside Rg3 is a promising anticancer agent. It is usually produced by heat treatment of ginseng, in which ginsenoside Rb1 is the major ginsenoside. A kinetic study was conducted to optimize ginsenoside Rg3 production by the heat treatment of ginsenoside Rb1. Methods: Ginsenoside Rb1 was heated using an isothermal machine at $80^{\circ}C$ and $100^{\circ}C$ and analyzed using HPLC. The kinetic parameters were calculated from the experimental results. The activation energy was estimated and used to simulate the process. The optimized parameters of ginsenoside Rg3 production are suggested based on the simulation. Results: The rate constants were $0.013h^{-1}$ and $0.073h^{-1}$ for the degradation of ginsenosides Rb1 and Rg3 at $80^{\circ}C$, respectively. The corresponding rate constants at $100^{\circ}C$ were $0.045h^{-1}$ and $0.155h^{-1}$. The estimated activation energies of degradation of ginsenosides Rb1 and Rg3 were 69.2 kJ/mol and 40.9 kJ/mol, respectively. The rate constants at different temperatures were evaluated using the estimated activation energies, and the kinetic profiles of ginsenosides Rb1 and Rg3 at each temperature were simulated based on the proposed kinetic model of consecutive reaction. The optimum strategies for producing ginsenoside Rg3 from ginsenoside Rb1 are suggested based on the simulation. With increased temperature, a high concentration of ginsenoside Rg3 is formed rapidly. However, the concentration decreases quickly after the reaching the maximal concentration value. Conclusion: The optimum temperature for producing ginsenoside Rg3 should be the highest temperature technically feasible below $180^{\circ}C$, in consideration of the cooling time. The optimum reaction time for heat treatment is 30 min.

• 약학회지
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• 제59권6호
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• pp.259-265
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• 2015

In recent, there are increasing reports about pharmacological activities of Crataegi Fructus which has been used for many centuries as medicinal and food sources in East Asia. However, its antifungal efficacy needs to be investigated. Thus, in the current study, we determined synergistic antifungal activity of the Crataegi Fructus extract (CFE) when combined with fluconazole (FLC) against disseminated candidiasis due to Candida albicans. This fungus is one of the most problematic fungal pathogens. Data resulting from a microdilution susceptibility test showed that CFE had a dose-dependent antifungal activity. When the extract was combined with FLC, the activity was synergistic. For example, the antifungal activity by the combination of CFE at $20{\mu}g/ml$ plus FLC at $0.1{\mu}g/ml$ was 4 times more effective than antifungal activity by FLC alone at the same concentration (P<0.05). In the murine model of disseminated candidiasis, the combination therapy potentiated resistance of mice, resulting in 80% of C. albicans-infected animals surviving the entire period of 40 days observation, whereas mice given CFE alone or FLC alone all died with 17 and 23 days, respectively, although they survived longer than the untreated control animals (P<0.05). The CFE's antifungal activity seemed to be related to the blockage of hyphal production of C. albicans yeast cells. In summary, CFE has a synergistic antifungal activity, which can be produced by combining CFE with FLC. Thus, our data strongly indicate that CFE may be a potential candidate as an antifungal agent for combination therapy.

• 약학회지
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• 제56권1호
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• pp.20-25
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• 2012

In Northeast Asia, Paeoniae Radix has been used in treatments of inflammation-causing diseases such as arthritis for many centuries. Paeoniflorin, one of the principle bioactive monoterpene glucosides from the paeony root, is reported to be mostly responsible for the effectiveness of the treatments. However, the anti-inflammatory effect of a monoterpene, paeoniflorigenone (PFG) which partially has the moiety of paeoniflorin minus a glucose structure is unknown. Thus, the aim of this work was to investigate anti-inflammatory activity of PFG. For the investigation, PFG activity on the NO (nitric oxide) production from LPS-stimulated macrophages, and the anti-inflammatory effect was tested in the animal model of septic arthritis caused by Candida albicans, a major etiological agent for septic arthritis. For induction of the arthritis, mice were administered with an emulsion of C. albicans cell wall (CACW) mixed with Complete Freund's Adjuvant (CFA) via footpad-injection (Day 0); PFG at a dose of 0.5 or 1 mg/mouse (25 or 50 mg/kg of body-weight) was given to the animals on Day 3, 6, and 9; footpads were scored for arthritis. Moreover, the PFG effect on proliferation of T-lymphocyte that causes aggravation of arthritis was additionally tested. Data resulting from those tests showed that PFG inhibited the NO production from the stimulated macrophage in a dose dependent manner (P<0.05), indicating that PFG is an anti-inflammatory. To confirm the in-vitro results, anti-inflammatory activity of PFG was determined against C. albicans-caused septic arthritis. Data showed that PFG-treatment reduced footpad-swelling which indicates that PFG has anti-arthritic effect (P<0.05), which is therapeutic. The anti-arthritic effect appeared to be mediated by PFG suppression of T-cell proliferation. Ultimately, PFG, a monoterpene component, has anti-inflammatory activity analogous to paeoniflorin. The anti-inflammatory activity treats the septic arthritis due to a pathogenic fungus C. albicans.

• 약학회지
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• 제52권5호
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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.

• Archives of Pharmacal Research
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• 제29권5호
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• pp.348-353
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• 2006

In this study, a 40% ethanol extract of Chinese yam flour (Dioscoreae rhizoma), containing $177{\pm}58{\mu}g/mL$ of dioscin, was tested in order to evaluate its pharmacological effects on the gastrointestinal tracts of Sprague-Dawley rats. Via the ingestion of the Chinese yam extract, the secretion of gastric acid was suppressed in the rats, and gastrointestinal motility increased by as much as 10%. The fecal quantity of rats fed on the Chinese yam extract also increased, by more than 40% as compared with that of the controls. The Chinese yam extract was found not to affect the growth of normal intestinal bacteria. However, a great deal of lactose-fermenting bacteria was observed in the fecal samples of rats fed for 6 weeks on 2% Chinese yam extract. This finding would appear to suggest that Chinese yam extract not only induces an improvement in digestive capability, but also affects the conversion of some intestinal flora to helpful bacteria. Our serochemical analyses indicated that serum glucose, neutral lipid, and total cholesterol levels were reduced to some degree by long-term feeding on Chinese yam extract. This finding bolsters the notion that Chinese yam extract may prove helpful as a digestion-aiding agent for patients suffering from hyperglycemia or hyperlipidemia.