• The Korean Journal of Pharmacology
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• v.31 no.2
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• pp.251-259
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• 1995

Pharmacokinetics and pharmacodynamics of metoprolol, a selective beta-l blocker, were examined for 360 minutes after intravenous bolus administration of metoprolol to 6 dogs. Plasma concentration and excreted amount in the urine metoprolol were measured by liquid chromatography with fluorescence detection. PR interval and heart rate were measured by ECG monitoring. Blood pressure was monitored through intraarterial catheter in femoral artery and cardiac output by thermodilution method using Swan-Ganz catheter. To analyze the effect site concentration-response relationship, plasma concentration and pharmacological effects were simultaneously fitted to a two pharmacokinetic compartment linked to pharmacodynamic model with NONLIN program. Results are as follows. 1) The plasma concentration of metoprolol after intrvenous injection decreased biexponentially. The terminal half-life estimated was $1.33{\pm}0.40$ hours and the volume of distribution at steady state (Vdss) and the total body clearance were $1.04{\pm}0.4\;L/kg,\;6.55{\pm}2.21\;L/hr$, respectively. The central compartment volume of distribution and peripheral compartment volume of distribution were $0.35{\pm}0.14L/kg\;and\;0.69{\pm}0.34L/kg$. The renal clearance and intercompartment clearance were $0.53{\pm}0.25\;L/min\;and\;0.35{\pm}0.19\;L/min$. 2) Simulated biophase concentration-response curve shows hyperbolic relationship and the estimated concentration-effect relationship was best explained by Emax model when the prolongation of PR interval and the reduction of the heart rate were used as pharmacodynamic parameters. Emax and EC50 were estimated to be $26.3{\pm}4.7\;msec\;and\;88.8{\pm}82.3\;g/ml$ for PR interval, and $48.7{\pm}18.8\;beats/min\;and\;113.5{\pm}78.7\;ng/ml$ for heart rate, respectively. 3) The changes of cardiac output-effect site concentration relationship was best fitted by a linear model and the slope of the relationship was $0.005{\pm}0.003$. Diastolic blood pressure-effect site concentration relationship was also explained by the linear model and the slope of the relationship was $0.038{\pm}0.034$.

• Journal of the East Asian Society of Dietary Life
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• v.24 no.3
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• pp.335-350
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• 2014

Compared to the large numbers of studies on the diabetes, hyperlipidemia and cancer therpeutic effects of ginseng, the anti-obese effect and mechanisms of ginsengs have not been studied as much. To determine the effects of ginseng on obesity, 14 keywords (ginseng, ginsenoside, obesity, weight, fat, diet, overeat, appetite, lipid, 3T3-L1, adipocyte, food intake, adipogenesis and lipolysis) were combined in searching a database. Fifty-six articles published from 1983 to 2012 as well as 656 patents registered until Aug $17^{th}$, 2012, were screened for anti-obese effects of ginseng. In the classification of experimental methods, 16 papers on 3T3-L1 cells, 38 papers on animals and three papers on human were reviewed. In terms of obese mechanisms of action, the most commonly used biomarkers were in order of lipid profiles > weight change > blood glucose > adipocytokine. Most ginseng studies on obesity focused on AMPK, $PPAR{\gamma}$, GLUT-4, PI3K and SREBP-1. Korean white ginseng extracts and Re repressed the lipogenesis genes such as PPARc2, SREBP-1c, LPL, FAS and DGAT1. However, ginseng or ginsenosides, PD (Rb1) and PT (Re), showed different or contradictory results. Water and ethanol extraction of ginseng showed contradictory effects on the secretion of inflammatory cytokines, wheras IL-6 was repressed by ethanol extracts and TNF-${\alpha}$ repressed by Re in vitro. Based on the literature, further studies on anti-obese mechanisms of ginseng, such as the inflammation-related obesity or cross signals between the adipocytes and the environments, are needed, instead of more studies on its hypolipidemic and hypoglycemic effects.

• Proceedings of the KIEE Conference
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• 1992.07b
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• pp.794-798
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• 1992

We present an optical Voltage and current sensor using $BSO(Bi_{12}SiO_{20})$ monocrystal. The voltage and current sensor consist of PBS(Polarizing Beam Splitter), 1/4 wavelength plate, ZnSe, Selfoc lens, LED, and PIN-PD etc. Magnetic core was made using permalloy for applying magnetic field to current sensor effectively. Current was measured from 100 to 1,600 ampere and accuracy was about ${\pm}$5%. The accuracy could be improved to ${\pm}$l% after reducing the nonlinear property of BSO crystal using our own program in PC (IBM286). We noticed that these data were not influenced by 154,000 voltage at all. Applied voltage was reduced to 1/20 using capacitors. And experiment was carried out up to 450V of the reduced voltage. The data fran optical voltage sensor was similar to that from conventional voltage sensor. The accuracy of the data was within about ${\pm}$1%.

• Journal of Gastric Cancer
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• v.18 no.1
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• pp.1-19
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• 2018

Gastric cancer (GC) is the second leading cause of cancer mortality and the fourth most commonly diagnosed malignant diseases. While continued efforts have been focused on GC treatment, the introduction of trastuzumab marked the beginning of a new era of target-specific treatments. Considering the diversity of mutations in GC, satisfactory results obtained from various target-specific therapies were expected, yet most of them were unsuccessful in controlled clinical trials. There are several possible reasons underlying the failures, including the absence of patient selection depending on validated predictive biomarkers, the inappropriate combination of drugs, and tumor heterogeneity. In contrast to targeted agents, immuno-oncologic agents are designed to regulate and boost immunity, are not target-specific, and may overcome tumor heterogeneity. With the successful establishment of predictive biomarkers, including Epstein-Barr virus pattern, microsatellite instability status, and programmed death-ligand 1 (PD-L1) expression, as well as ideal combination regimens, a new frontier in the immuno-oncology of GC treatment is on the horizon. Since the field of immuno-oncology has witnessed innovative, practice-changing successes in other cancer types, several trials on GC are ongoing. Among immuno-oncologic therapies, immune checkpoint inhibitors are the mainstay of clinical trials performed on GC. In this article, we review target-specific agents currently used in clinics or are undergoing clinical trials, and highlight the future clinical application of immuno-oncologic agents in inoperable GC.

• Biomedical Science Letters
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• v.28 no.1
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• pp.25-33
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• 2022

The imbalance of oxidative stress due to the excessive production of reactive oxygen species (ROS) leads to the pathogenesis of liver disease. To prevent this, the role of antioxidant mechanisms is important. Antioxidant studies have been reported on the Filipendula glaberrima Nakai. However, studies applied to HepG2 cells, which are human liver cells, have not yet been conducted. In this study, 70% ethanol extract of Filipendula glaberrima Nakai (FGE) was prepared and antioxidant activity was investigated. It was confirmed whether FGE pretreatment could reduce hydrogen peroxide-induced oxidative stress in HepG2 cells. The increase in gene expression of antioxidant biomarkers and the scavenging ability of ROS were measured, and Hoechst 33342 staining was used to know the inhibitory effect of the apoptosis. As a result, FGE significantly increased SOD (2.6-fold), CAT (4.4-fold), MT-1A (3.1-fold), GPx (4-fold), and G6PD (2.4)-fold compared to the H₂O₂-treated group. FGE directly inhibited ROS production from 13.4 to 3.6 (the fluorescence mean of DCF-DA) and also reduced apoptotic cells from 45% to 10% (Hoechst 33342 staining) at 2.5 ㎍/mL. These results demonstrate the excellent antioxidant activity of FGE and show that it can be used as a functional food to prevent liver disease.

• Journal of Ginseng Research
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• v.38 no.3
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• pp.173-179
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• 2014

Background: Ginsenosides are the major components responsible for the biochemical and pharmacological actions of ginseng, and have been shown to have various biological activities. In this study, we investigated the antiviral activities of seven ginsenosides [protopanaxatriol (PT) type: Re, Rf, and Rg2; protopanaxadiol (PD) type: Rb1, Rb2, Rc, and Rd)] against coxsackievirus B3 (CVB3), enterovirus 71 (EV71), and human rhinovirus 3 (HRV3). Methods: Assays of antiviral activity and cytotoxicity were evaluated by the sulforhodamine B method using the cytopathic effect (CPE) reduction assay. Results: The antiviral assays demonstrated that, of the seven ginsenosides, the PT-type ginsenosides (Re, Rf, and Rg2) possess significant antiviral activities against CVB3 and HRV3 at a concentration of $100{\mu}g/mL$. Among the PT-type ginsenosides, only ginsenoside Rg2 showed significant anti-EV71 activity with no cytotoxicity to cells at $100{\mu}g/mL$. The PD-type ginsenosides (Rb1, Rb2, Rc, and Rd), by contrast, did not show any significant antiviral activity against CVB3, EV71, and HRV3, and exhibited cytotoxic effects to virus-infected cells. Notably, the antiviral efficacies of PT-type ginsenosides were comparable to those of ribavirin, a commonly used antiviral drug. Conclusion: Collectively, our findings suggest that the ginsenosides Re, Rf, and Rg2 have the potential to be effective in the treatment of CVB3, EV71, and HRV3 infection.

• Nuclear Engineering and Technology
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• v.30 no.2
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• pp.99-111
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• 1998

Chemical composition of the insoluble residue in a simulated spent PWR fuel(SIMRJEL) were studied. SIMFUELS were prepared by adding calculated amount of FP(fission product) elements with a burnup of 3.6% FIMA(fission per initial metal atom) to uranium in nitrate solution, evaporating the mixed solution to dryness, calcining at 90$0^{\circ}C$ in a stream of 4% H$_2$ + 96% He, and heating the pellet at 140$0^{\circ}C$ under high and low oxygen potentials. Insoluble residue was obtained from the dissolution of the SIMFUEL with HNO$_3$(1 : 1). The chemical composition of the SIMFUELs and the insoluble residues was determined by EPMA(electron probe microanalysis), XPS(X-ray photoelectron spectroscopy) and by XRD (X-ray diffraction) measurements. All of the insoluble residues suspended and precipitated were composed mainly of Mo, Ru with a small amount of Zr, Rh, Pd and Cd. The amount of insoluble residue(<1 wt.%) and a Mo/Ru ratio decreased with increasing oxygen potential. Formation of the zirconium molybdate precipitate, ZrMo$_2$O$_{7}$(OH)$_2$($H_2O$)$_2$, was observed in the residues. The possible role of Mo on the phase formation was discussed in regard to oxygen potential.l.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.1965-1967
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• 2013

Background: To obtain the maximum additional information about the prognosis of gastric cancer, we compared CA-50 with other previously defined markers. Materials and Methods: This hospital based study was carried out in the Department of Biochemistry of Nepalese Army Institute of Health Sciences between $1^{st}$ July 2012 and $31^{st}$ December 2012. The variables collected were age, gender, AFP, CEA, CA19-9, and CA50, assayed with ELISA reader for all cases. The cut off values for serum AFP, CEA, CA19-9, and CA-50 were 10 ${\mu}g/l$, 10 ${\mu}g/l$, 37 U/ml, and 20 U/ml, respectively according to the manufacturer's instructions. Approval for the study was obtained from the institutional research ethical committee. Results: Of the 40 examined patients, 13 patients had tumors located in the upper third of the stomach, 6 patients had tumors in the middle third, 16 patients had tumors in the lower third, and 5 patients had tumors occupying two-thirds of the stomach or more. The distribution of lymph node staging of the patients was as follows: 7 patients belonged to N0, 9 patients to N1 stage, 10 patients to N2 stage, and 14 patients to N3 stage. The statistical method of Cox proportional hazards using multivariate analysis also illustrated that tumor markers including CEA (2.802), CA19-9 (2.690), CA50 (2.101), were independent prognostic factors, as tumor size (1.603), and lymph node stage (1.614). Conclusions: The tumour markers now available, like CEA, CA 19-9 and CA 50, chiefly perceive advanced gastric cancer. The preoperative rise in those tumour marker level have a prognostic significance and may be clinically helpful in choosing patients for adjuvant management.

• Journal of Life Science
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• v.13 no.6
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• pp.849-855
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• 2003

Nitric oxide (NO) plays an important role as a signaling molecule in the proliferation of placenta trophoblasts. In this study, we investigated the effect of NO on the activation of phospholipase C (PLC) in BeWo cells, choriocar-cinoma cell line. Sodium nitroprusside (SNP), an agent to produce NO spontaneously in cells, alone increased $［^3H］$ thymidine incorporation of BeWo cells, indicating NO stimulates proliferation of the cells. NO-induced proliferation of BeWo cells was blocked by U73122, an inhibitor of PLC, suggesting that NO-induced PLC activation is involved in the cell proliferation. NO also stimulated extracellular signal-regulated kinase (ERK) in BeWo cells, indicated by increased phosphorylation of ERK1/2 in Western blotting using anti-phospho-ERK1/2 antibody. NO-induced phos-phorylation of ERK1/2 was not abrogated by U73122. $PLC\gamma_1$l but not$PLC\gamma_2$ was tyrosine phosphorylated by SNP in immunoprecipitation assay using anti-$PLC\gamma_1$/$PLC\gamma_2$ antibodies, and SNP-induced phosphorylation of $PLC\gamma_1$ was abrogated by pre-treatment of cells with genistein and PD98059, indicating that NO induced-phosphorylation of $PLC\gamma_1$ is mediated by ERK. These results suggest that NO stimulates the proliferation of BeWo cells through ERK and $PLC\gamma_1$.

• Korean Journal of Plant Resources
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• v.31 no.4
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• pp.363-371
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• 2018

Tiarella polyphylla D. Don is a native plant distributed only in Ulleung Island in Korea and has been traditionally used for medicinal purposes, although it is also used ornamentally. This study was conducted to determine the requirements for dormancy break and germination and to classify the type of seed dormancy. The experiments were performed with cold stratification (0 or 12 weeks at $5^{\circ}C$), warm stratification (0, 4, 8, or 12 weeks at $23^{\circ}C$, followed by 8 weeks at $5^{\circ}C$, and then incubation at $23^{\circ}C$), and $GA_3$ treatments (0, 10, 100, or 1000 mg/L). The treated seeds were incubated on aseptic media at room chamber ($23^{\circ}C$, a 16h photoperiod of fluorescent lamps with $40{\mu}mol{\cdot}m^{-2}{\cdot}s^{-1}$). The seeds were dispersed in nature as underdeveloped embryos with no physical barrier to absorb water to prevent water absorption. However, the seeds did not germinate for 30 days after sowing without any pre-treatments. Thus, the seeds had morphological dormancy (MD) and physiological dormancy (PD). The final germination percentage following cold stratification (0 or 12 weeks) was 66.7% and 45.6%, respectively. The cold stratification delayed seed germination by about 3 weeks. In the warm stratification experiment (0, 4, 8, or 12 weeks), the final germination percentage was 21.1%, 27.8%, 41.1%, and 57.8%, respectively, 20 weeks after sowing. The embryos of the T. polyphylla seed grew in relatively warm temperatures ($23^{\circ}C$). $GA_3$ application overcame seed dormancy and promoted germination. Following $GA_3$ treatment (0, 10, 100, or 1000 mg/L), the final germination percentage was 33.3%, 45.0%, 42.5%, and 72.5%, respectively. These results suggest that the T. polyphylla seeds had non-deep simple morphophysiological dormancy (MPD) and $GA_3$ treatment could be used as a substitute for warm stratification for breaking seed dormancy. To our knowledge, this is the first report of seed dormancy characteristics of the genus Tiarella native to Korea.