• YAKHAK HOEJI
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• v.39 no.4
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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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• v.34 no.3
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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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• v.17 no.2
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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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• v.37 no.12
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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.

• Journal of the Microelectronics and Packaging Society
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• v.21 no.3
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• pp.43-50
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• 2014

By the trends of electronic package to be smaller, thinner and more integrative, the reliability of interconnection between Si chip and printed circuit board is required. This paper reports on a study of high speed shear energy of Sn-4.0wt%Ag-0.5wt%Cu (SAC405) solder joints with different the thicknesses of electroless Ni-P deposit. A high speed shear testing of solder joints was conducted to find a relationship between the thickness of Ni-P deposit and the brittle fracture in electroless Ni-P deposit/SAC405 solder. A focused ion beam (FIB) was used to polish the cross sections to reveal details of the microstructure of the fractured pad surface with and without $HNO_3$ vapor treatment. The high speed shear energy of SAC405 solder joint with $1{\mu}m$ Ni-P deposit was found to be lower without $HNO_3$ vapor, compared to those of over $3{\mu}m$ Ni-P deposit. This could be due to the edge of solder resist in $1{\mu}m$ Ni-P deposit, which provides a fracture location for the weakened shear energy of solder joints and brittle fracture in high speed shear test. With $HNO_3$ vapor, the brittle fracture mode in high speed shear test decreased with increasing the thickness of Ni-P deposit. Then the roughness (Ra) of Ni-P deposits decreased with increasing its thickness. Thus, this gives the evidence that the decrease in roughness of Ni-P deposit for Eelectroless Ni/ Electroless Pd/ Immersion Au (ENEPIG) surface play a critical role for improving the robustness of SAC405 solder joint.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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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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• v.40 no.2
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• pp.157-162
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• 1997

A novel compound, named YH-487, was synthesized by attaching the thiol and aminothiazole residue to $C_3$ and $C_7$ position of 7-aminocephalosporanic acid (7-ACA). The therapeutic efficacy on infected animals, pharmacokinetics in vivo and the effect on intestinal microflora of YH-487 were examined. The pharmacokinetics of YH-487 were similar to that of cefotaxime, a third generation ${\beta}-lactam$ antibiotics, in rat. Upon in vivo administration, YH-487 was predominantly delivered to kidney, and mostly excreted through kidney without making any metabolites. The therapeutic efficacy of YH-487 to animal infected with E. coli was three times and twenty times higher than that of cefotaxime and cefotiam, respectively, In vivo administration of YH-487 to Sprague-Dawley rats significantly decreased the population of intestinal gram negative species such as Enterobacteria and Barteroides. However, no significant changes were obseved in gram positive species such as Lactobacillus, Bifidobacteria and Staphylococcus. In addition, continuous administration of YH-487 did not increase the possibility to induce resistant strains in intestinal microflora.

• Restorative Dentistry and Endodontics
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• v.22 no.1
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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.

• Journal of the Korean Magnetics Society
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• v.18 no.1
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• pp.1-8
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• 2008

We have manufactured and evaluated reference samples for the use of low magnetic moment measurements. Before the measurements, SQUID magnetometers were magnetically shielded from external magnetic noise. We considered the purity including magnetic impurities, the optimum thickness, the modification method, and the shape in the preparation of the samples. Three paramagnetic polycrystaline metal plates of Ti, W, and Al with the area of $4mm{\times}6mm$ were prepared finally. The magnetic moments of these three samples are measured very linear up to the field of 5 T without magnetic hysteresis. The temperature deviated ratios of the magnetic moments for Ti, Al, and W from 290 K to 310 K are 0.7, 1.5, and 0.1 %, respectively. The measured magnetic moments for Ti and W samples by our research team are very well agreeable with those by two SQUID magnetometers and a VSM at Quantum Design via international round robin test. The results suggest that the prepared reference samples are well suited for the use in the low magnetic moment measurement with SQUID based magnetometers.

• The Journal of Korean Academy of Prosthodontics
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• v.31 no.3
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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.