• 약학회지
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• 제39권4호
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• pp.360-366
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• 1995

1-$\beta$-Methyl carbapenem-2-substituted pyrroudine derivatives. CRB 529 and CRB 550, were synthesized as investigational carbapenem derivatives. It has been reported that the in vitro antibacterial activities of the compounds against G(+) and G(-) bacteria were almost the same or more effective than those of imipenem (IPM) and meropenem (MEPM), and also showed better in vivo efficacy than MEPM and inlipeneni/cilastatin (IPM/CS) against representative G(-) organisms, P. aeruginosa and MRSA organisms, S. aureus. The antibacterial activities, pharmacokinetics and protective efficacy of IPM/CS and CRB 529 and CRB 550 wereconducted after subcutaneous or intravenous administration to mice and rats. The pharmacokinetic parameters of CRB 529 and CRB 550 in mice were as follows: the observed maximal serum concentrations (C$_{max}$) following I.V. administration were 87.5 and 101 $\mu\textrm{g}$/ml for CRB 529 and CRB 550, respectively, and 63.6 $\mu\textrm{g}$/ml for IPM/CS. The half-lives (t$_{1/2}$) were 14.0 and 12.0 n-dn for CRB 529 and CRB 550, respectively, and 14.8 min for IPM/CS. In rats, $C_{max}$ after I.V. administration were 74.0 and 91.8 $\mu\textrm{g}$/ml for CRB 529 and CRB 550, respectively, and 41.2 $\mu\textrm{g}$/ml for IPM/CS. The tissue levels of CRB 529 and CRB 550 and IPM/CS after I.V. administration at a dose of 20 mg/kg decreased by the following order: lung, heart, kindney, liver and spleen for CRB 529, lddney, liver. lung, heart and spleen for CRB 550 and kidney, lung, liver, heart, spleen and brain for IPM/CS. In systemic infection, CRB 529 and CRB 550 showed excellent efficacies against P. aeruginosa and S. aureus (MRSA) at a dose of 5 mg/kg. The PD$_{50s}$ were 0.80, 0.36 mg/kg for CRB 529 and CRB 550, respectively, and 3.22 mg/kg for IPM/CS against P. aeruginosa. The corresponding values against S. aureus (MRSA) were 76.0, 55.3 mg/kg for CRB 529 and CRB 550, respectively, and 146 mg/kg for IPM/CS. In local infection, the antibacterial activities of CRB 529 and CRB 550 were more effective than those of IPM/CS against intrarenal infection with E. coli and P. aeruginosa and also showed as effective as IPM/CS against respiratory tract infection with E. coli and P. aeruginosa at a dose of 5 mg/kg.

• BMB Reports
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• 제34권3호
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• pp.237-243
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• 2001

Taxol, a natural product extracted from the Taxus brevifolia, is known to have significant anti-tumor activities against many common cancers, including ovarian and breast cancers. Despite the pronounced anti-tumor activity of this compound, its poor solubility in aqueous solutions hampers its clinical applications. We studied the anticancer mechanisms of the water-soluble taxol diethylenetriamine pentaacetate (DTPA) used for radiolabeling, and compared it to that of taxol. In vitro cytotoxicities of taxol and taxol-DTPA conjugate were tested in HT29 human colorectal cancer cells by the MTT method. As the result, the $IC_{50}$ value of the taxol-DTPA conjugate was about three fold higher than that of taxol. When analyzed by an agarose gel electrophoresis, the DNA ladders became evident after the incubation of cells with the taxol-DTPA conjugate for 24 h. We also found morphological changes of the cells undergoing apoptosis with electron microscopy Next, we examined the signal pathway of taxol-DTPA conjugate-induced apoptosis in HT29 cells. The activation of extracellular signal-regulated protein kinase (ERK1/2) occurred at 10, 30, 60 and 120 min after 200 nM taxol-DTPA conjugate treatment. The pretreatment of the MEK inhibitor (PD98059) completely blocked the taxol-DTPA conjugate-induced ERK1/2 activation. The activated ERK1/2 translocated into the nucleus at the same time and phosphorylated its transcriptional factor, c-Jun. These results suggest that the taxol-DTPA conjugate has an apoptotic activity in HT29 cells, and that its proapoptic activity might be related with the signal transduction via ERK1/2 and c-Jun similar to that of taxol.

• The Korean Journal of Physiology and Pharmacology
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• 제17권2호
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• pp.127-132
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• 2013

Ginsenosides, one of the active ingredients of Panax ginseng, show various pharmacological and physiological effects, and they are converted into compound K (CK) or protopanaxatriol (M4) by intestinal microorganisms. CK is a metabolite derived from protopanaxadiol (PD) ginsenosides, whereas M4 is a metabolite derived from protopanaxatriol (PT) ginsenosides. The ${\gamma}$-aminobutyric acid $receptor_C$ ($GABA_C$) is primarily expressed in retinal bipolar cells and several regions of the brain. However, little is known of the effects of ginsenoside metabolites on $GABA_C$ receptor channel activity. In the present study, we examined the effects of CK and M4 on the activity of human recombinant $GABA_C$ receptor (${\rho}$ 1) channels expressed in Xenopus oocytes by using a 2-electrode voltage clamp technique. In oocytes expressing $GABA_C$ receptor cRNA, we found that CK or M4 alone had no effect in oocytes. However, co-application of either CK or M4 with GABA inhibited the GABA-induced inward peak current ($I_{GABA}$). Interestingly, pre-application of M4 inhibited $I_{GABA}$ more potently than CK in a dose- dependent and reversible manner. The half-inhibitory concentration ($IC_{50}$) values of CK and M4 were $52.1{\pm}2.3$ and $45.7{\pm}3.9{\mu}M$, respectively. Inhibition of $I_{GABA}$ by CK and M4 was voltage-independent and non-competitive. This study implies that ginsenoside metabolites may regulate $GABA_C$ receptor channel activity in the brain, including in the eyes.

• Molecules and Cells
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• 제37권12호
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• pp.899-906
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• 2014

Prostaglandin $E_2$ ($PGE_2$) promotes tumor-persistent inflammation, frequently resulting in cancer. Curcumin is a diphenolic turmeric that inhibits carcinogenesis and induces apoptosis. $PGE_2$ inhibits curcumin-induced apoptosis; however, the underlying inhibitory mechanisms in colon cancer cells remain unknown. The aim of the present study is to investigate the survival role of $PGE_2$ and whether addition of exogenous $PGE_2$ affects curcumininduced cell death. HCT-15 cells were treated with curcumin and $PGE_2$, and protein expression levels were investigated via Western blot. Reactive oxygen species (ROS) generation, lipid peroxidation, and intracellular glutathione (GSH) levels were confirmed using specific dyes. The nuclear factor-kappa B ($NF-{\kappa}B$) DNA-binding was measured by electrophoretic mobility shift assay (EMSA). $PGE_2$ inhibited curcumin-induced apoptosis by suppressing oxidative stress and degradation of PARP and lamin B. However, exposure of cells to the EP2 receptor antagonist, AH6809, and the PKA inhibitor, H89, before treatment with $PGE_2$ or curcumin abolished the protective effect of $PGE_2$ and enhanced curcumin-induced cell death. $PGE_2$ activates PKA, which is required for cAMP-mediated transcriptional activation of CREB. $PGE_2$ also activated the Ras/Raf/Erk pathway, and pretreatment with PD98059 abolished the protective effect of $PGE_2$. Furthermore, curcumin treatment greatly reduced phosphorylation of CREB, followed by a concomitant reduction of $NF-{\kappa}B$ (p50 and p65) subunit activation. $PGE_2$ markedly activated nuclear translocation of $NF-{\kappa}B$. EMSA confirmed the DNA-binding activities of $NF-{\kappa}B$ subunits. These results suggest that inhibition of curcumin-induced apoptosis by $PGE_2$ through activation of PKA, Ras, and $NF-{\kappa}B$ signaling pathways may provide a molecular basis for the reversal of curcumin-induced colon carcinoma cell death.

• 마이크로전자및패키징학회지
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• 제21권3호
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• pp.43-50
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• 2014

전자 제품의 경박 단소화 및 고집적화가 이루어 지면서 실리콘 집과 인쇄회로기판의 인터커넥션의 고신뢰도가 요구되고 있다. 본 연구는 Sn-4.0wt%Ag-0.5wt%Cu (SAC405) 솔더와 다양한 무전해 Ni-P 도금 두께에서의 high speed shear 에너지 및 파괴 모드를 연구하였다. 파괴 모드 분석을 위하여 집속이온빔(FIB) 분석이 이용되었다. 질산 기상 처리하지 않은 $1{\mu}m$ Ni-P 시편에서 낮은 shear 에너지가 나왔으며, 이는 솔더레지스트 선단에서 파단의 원인을 제공하는 것이 확인되었다. 질산 기상 처리한 시편에서 무전해 Ni-P 도금 두께가 커질수록 취성 파괴 모드는 감소한다. 또 Ni-P 도금 두께와 표면 거칠기(Ra)는 반비례 관계를 가진다. 이는 Ni-P 도금의 표면 거칠기를 낮추면 SAC405 솔더 조인트의 신뢰도를 향상시킨다는 사실을 나타낸다.

• Asian Pacific Journal of Cancer Prevention
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• 제17권4호
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• pp.2137-2140
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• 2016

Background: Gall bladder cancer (GBC) usually presents as unresectable or metastatic disease. We conducted a feasibility study to evaluate the effect of neoadjuvant therapy (NAT) on radiologic downstaging and resectability in unresectable GBC cases. Materials and Methods: Patients with locally advanced disease were treated with chemoradiotherapy [CTRT] ( external radiotherapy (45Gy) along with weekly concurrent cisplatin $35mg/m^2$ and 5-FU 500 mg) and those with positive paraaortic nodes were treated with neoadjuvant chemotherapy [NACT (cisplatin $25mg/m^2$ and gemcitabine $1gm/m^2$ day 1 and 8, 3 weekly for 3 cycles). Radiological assessment was according to RECIST criteria by evaluating downstaging of liver involvement and lymphadenopathy into complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Results: A total of 40 patients were evaluated from January 2012 to December 2014 (CTRT=25, NACT=15). Pretreatment CT scans revealed involvement of hilum (19), liver infiltration (38), duodenum involvement (n=22), colon involvement (n=11), N1 involvement (n=11), N2 disease (n=8), paraaortic LN (n=15), and no lymphadenopathy (n=6). After neoadjuvant therapy, liver involvement showed CR in 11(30%), PR in 4 (10.5%), SD in 15 (39.4%) and lymph node involvement showed CR in 17 (50%), PR in 6 (17.6%), SD in 4 (11.7 %). Six patients (CTRT=2, NACT=4) with 66.6 % and 83% downstaging of liver and lymphnodes respectively underwent extended cholecystectomy. There was 16.6 % and 83.3% rates of histopathological CR of liver and lymph nodes. All resections were R0. Conclusions: Neoadjuvant therapy in unresectable gall bladder cancer results in a 15% resectability rate. This approach has a strong potential in achieving R0 and node negative disease. Radiologic downstaging (CR+PR) of liver involvement is 40.5% and lymphadenopathy is 67.5%. Nodal regression could serve as a predictor of response to neoadjuvant therapy.

• Applied Biological Chemistry
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• 제40권2호
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• pp.157-162
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• 1997

Cephem계 항생물질의 기본 구조인 7-aminocephalosporanic acid (7-ACA)의 $C_3$ 위치에 thiol기를 도입하고 $C_7$ 위치 aminothiazole기를 결합시킨 신규 화합물(YH-487)에 대한 감염치료효과, 체내동태 그리고 이의 투여에 의한 흰쥐의 장내균총들의 영향에 관하여 검토한 결과, YH-487을 흰쥐에 꼬리정맥을 통하여 20mg/kg으로 투여시 혈중 최고농도 등 체내동태는 제 3세대 ${\beta}-lactam$계 약물인 cefotaxime 등과 유사한 결과를 보였으며 장기조직으로의 이행성은 신장으로의 이행율이 가장 좋았고 배설은 신장 배설 타입이었으며 배설된 약물은 체내의 대사에 의한 변화를 받지 않았다. 또한 YH-487의 대장균 감염증에 대한 치료효과는 cefotaxlme의 3배, cefotiam의 약 20배 정도 높았다. 한편 YH-487의 투여에 의한 흰쥐의 장내 균총의 변화는 Enterobacter와 Bacteroides속 등 Gram 음성 세균은 투여 후 균수가 크게 감소 하였으나 Lactobacillus, Bifidobacterium과 Staphylococcus속 등 Gram 양성 세균은 영향을 받지 않았다. 또한 YH-487을 연속 투여한 후 분리한 균주의 항균활성은 투여전의 균주와 차이가 없어 내성균의 출현 가능성이 낮았다.

• Restorative Dentistry and Endodontics
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• 제22권1호
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• pp.396-412
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• 1997

The purpose of this study is to observe the corrosion characteristics of five dental amalgams(CAULK FINE CUT, OPTALLOY II, DISPERSALLOY, TYTIN, and VALIANT) in the solutions with fluoride compound through the anodic polarization curve obtained by using a potentiostat. After each amalgam alloy and Hg being triturated, the triturated mass was inserted into the cylindrical metal mold, and condensed by hydraulic pressure(160 kg/$cm^2$). Each specimen was removed from the metal mold. Specimens were polished with the silicone carbide grinding paper 24 hours after condensation and stored at room temperature for 1 week. The anodic polarization curves were employed to compare the corrosion behaviours of the amalgams in 0.9 % saline solution and in the saline solutions with 2.2 ppm, 0.05 %, 2 % NaF, and 8 % $SnF_2$ at $37^{\circ}C$ with 3-electrode potentiostat. After the immersion of specimen in electrolyte for 30 minutes, the potential scan was begun. The potential scan range was -1500m V to + 800m V(vs. S.C.E.) in the working electrode and the scan rate was 50 mV/sec. The results were as follows, 1. The corrosion potential, the potential of anodic current peak, and transpassive potential in the saline solutions with NaF shifted to lower direction than those in normal saline solution, and the current density in the saline solutions with NaF was higher than that in normal saline solution. The differences were increased as the concentrations of NaF became higher. 2. The corrosion potential and transpassive potential in the saline solution with $SnF_2$ shifted to higher direction than those in normal saline solution, and the current density in the saline solution with $SnF_2$ was higher than that in normal saline solution after the corrosion potential. The anodic polarization curves in the saline solution with $SnF_2$ had no outstanding anodic current peak. 3. The corrosion potentials for high-copper amalgams were much higher than those for CAULK FINE CUT and OPTALLOY II in normal saline solution, but, as the concentrations of fluoride compound became higher, the differences in corrosion potentials between them were decreased. The corrosion potentials had the similarity in the saline solution with 2% NaF or 8% $SnF_2$. 4. The current density for TYTIN was the lowest among the others in normal saline solution and in the saline solution with 2.2 ppm or 0.05 % NaF. 5. There was no significant difference in current density between Pd-enriched VALIANT and other high-copper amalgams.

• 한국자기학회지
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• 제18권1호
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• pp.1-8
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• 2008

최근 발전하는 초박막 자기 시료의 정확한 자기 모멘트 측정을 위하여 저자기 모멘트 표준 시료를 제작하였다. 정밀한 저자기 모멘트 표준시료를 제작하기 위해서 자력계를 미리 자기잡음으로부터 차폐시켰고, 시료준비과정에서 강자성 불순물을 고려한 시료의 순도, 절단 방법, 시료의 모양과 두께 등을 고려하였다. 본 연구에서는 SQUID 자력계를 이용한 자기 모멘트 측정에 적합하게 $4mm{\times}6mm$ 면적을 갖는 Al, Ti과 W로 된 판상형 시료 3 개를 준비하였다. Pd 금속의 경우는 이미 잘 보정된 실린더형 시료를 사용하였다. 준비된 세 개의 판상형 시료의 경우 50,000 Oe 이내의 자기장영역에서 자기이력현상이 관측되지 않았고 모두 양호한 선형성을 보였다. 290K에서 310K까지의 온도영역에서 Ti, Al, W의 자기모멘트 값의 변화는 각각 0.7%, 1.5%, 0.1% 이내로 작았다. 본 연구에서 준비된 각각의 시편에 대해 자기모멘트 값을 결정하였으며, round robin test를 통하여 측정값의 신뢰도를 확인하였다. 그 결과 본 연구에서 제작한 표준시료는 저자기 모멘트 측정에 편리하고 적합하게 활용될 수 있음을 알 수 있었다.

• 대한치과보철학회지
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• 제31권3호
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• pp.423-446
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• 1993

Titanium and its alloys are finding increasing use in medical devices and dental implants. The strong selling point of titanium is its resistance to the highly corrosive body fluids in which an implant must survive. This corrosion resistance is due to a tenacious passive oxide or film which exists on the metal's surface and renders it passive. Potentiodynamic polarization measurement is one of the most commonly used electro-chemical methods that have been applied to measure corrosion rates. And the potentiodynamic polarization test supplies detailed information such as open circuit, rupture, and passivation potential. Furthermore, it indicates the passive range and sensitivity to pitting corrosion. This study was designed to compare the corrosion resistance of the commonly used dental implant materials such as CP Ti, Ti-6A1-4V, Co-Cr-Mo alloy, and 316L stainless steel. And the effects of galvanic couples between titanium and the dental alloys were assessed for their useful-ness-as. materials for superstructure. The working electrode is the specimen , the reference electrode is a saturated calomel electrode (SCE), and the counter electrode is made of carbon. In $N_2-saturated$ 0.9% NaCl solutions, the potential scanning was performed starting from -800mV (SCE) and the scan rate was 1 mV/sec. At least three different polarization measurements were carried out for each material on separate specimen. The galvanic corrosion measurements were conducted in the zero-shunt ammeter with an implant supraconstruction surface ratio of 1:1. The contact current density was recorded over a 24-hour period. The results were as follows : 1. In potential-time curve, all specimens became increasingly more noble after immersion in the test solution and reached between -70mV and 50mV (SCE) respectively after 12 hours. 2. The Ti and Ti alloy in the saline solution were most resistant to corrosion. They showed the typical passive behavior which was exhibited over the entire experimental range. Therefore no breakdown potentials were observed. 3. Comparing the rupture potentials, Ti and Ti alloy had the high(:st value (because their break-down potentials were not observed in this study potential range ) followed by Co-Cr-Mo alloy and stainless steel (316L). So , the corrosion resistance of titanium was cecellent, Co-Cr-Mo alloy slightly inferior and stainless steel (316L) much less. 4. The contact current density sinks faster than any other galvanic couple in the case of Ti/gold alloy. 5. Ag-Pd alloy coupled with Ti yielded high current density in the early stage. Furthermore, Ti became anodic. 6. Ti/Ni-Cr alloy showed a relatively high galvanic current and a tendency to increase.