• Journal of Acupuncture Research
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• v.32 no.1
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• pp.23-36
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• 2015

Objectives : This study was designed to investigate the neuroprotective effects of Hominis-Placenta (HP)on dopaminergic neurons. Methods : We examined the effect of invitro administration of HP against 1-methyl-4-phenylpyridinium( MPP+)-induced dopaminergic cell loss in primary mesencephalic culture and also used behavioral tests and performed analysis in the striatum and the substantia nigra of mouse brain, to confirm the effect of HP on dopaminergic neurons in an invivo 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced PD mouse model. Animals were assigned to four groups: (1) Group 1(vehicle-treatedgroup), (2) Group 2(MPTPonlytreated group), (3) Group 3(MPTP+ saline-treated/$ST_{36}$ group), and (4) Group 4(MPTP+HP-treated/$ST_{36}$ group). HP at $20{\mu}L$ of 48 mg/kg dose was injected at $ST_{36}$ for 4 weeks at 2-day intervals. MPTP in saline was injected intraperitoneally each day for 5 days from the $8_{th}$ treatment of HP. We performed the pole test and rota-rod test on the first and seventh day after the last MPTP injection. To investigate the effect of HP on dopaminergic neurons, we performed analysis in the striatum and the substantia nigra of mouse brain after treatment with HP and/or MPTP. Results : Treatment with HP had no influence on cell proliferation and caused no cell toxicity in $PC_{12}$ and $HT_{22}$ cells. Our study showed that HP significantly prevented cell loss and protected neurites against MPP+ toxicity. Although the invivo treatment of HP herbal acupuncture at $ST_{36}$ showed a tendency to improve movement ability and protected dopaminergic cells and fibers in the substantia nigra and the striatum, it did not show significant changes compared with the MPTP treated group. Conclusions : These data suggest that HP could be a potential treatment strategy in neurodegenerative diseases such as Parkinson's disease.

• Korean Journal of Clinical Pharmacy
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• v.30 no.1
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• pp.11-18
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• 2020

Background: Nivolumab and pembrolizumab are antagonists of the programmed death-ligand 1 (PD-L1) receptor that function as immuno-oncological agents. This study aimed to evaluate the safety and efficacy of nivolumab and pembrolizumab in elderly patients in outpatient settings. Methods: The safety and efficacy of nivolumab and pembrolizumab were compared retrospectively among patients at the Veterans Health Service (VHS) Medical Center in Seoul, South Korea, from September 1, 2017 to August 25, 2018. Results: Eighty-seven patients were selected for the study. The median progression-free survival was 63 days for nivolumab (95% confidence interval (CI), [14 to 282]) vs. 243 days for pembrolizumab (95% CI, [22 to 348]) (p =0.04). The objective response rate (ORR) was 0% in the nivolumab group vs 5.6% in the pembrolizumab group (p =0.310). All the patients exhibited treatment-related adverse effects. More than 89% of the patients exhibited diseases of the gastrointestinal (GI) tract. Pneumonia, of grades three or higher, was the most common adverse effect, followed by weakness and anorexia. Conclusions: There was no statistically significant difference between the nivolumab group and the pembrolizumab group with respect to the ORR. The incidence and severity of the adverse effects in this study were higher than those of previous studies; however, these adverse effects are generally manageable in a real-world clinical setting. Further randomized controlled studies will be necessary to confirm these results in elderly patients.

• 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 $0.038{\pm}0.034$.

• Korean Journal of Agricultural Science
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• v.14 no.2
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• pp.263-271
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• 1987

The cyclical trend and seasonal variations of chestnut prices have been analyzed to find out the chestnut price fluctuation in Korea during 1966-1985. The optimum prices, production, and plantation area for the next twenty five years (1986-2010) have been forcasted by the derived equation models. The results of study can be summarized as follows: 1. The chestnut prices were increased by 14.67 percent per annum during 1966-1972, an d decreased by 9.24 percent during 1973-1985, due to the excessive production of chestnut. 2. The chestnut prices showed the lowest price during the harvesting season, especially in October (89.1), and highest in July (109.1). Seasonal fluctuation of chestnut prices were 0.0837 (C.V value) during 1966-1975, and 0.0706 during 1976-1985. Such a seasonal fluctuation of chestnut prices tends to be even with the passage of time. 3. The equation model of predicted chestnut prices was derived as follows : PR=117788.088 - 7.60 TC/Pop + 6.585 GNP/Pop The chestnut prices will be the lowest in 1988, but increased rapidly thereafter. 4. The equation model of optimum chestnut production was derived as follows : $${\ell}n\;PD/Pop=-8.5147-0.8267{\ell}n\;PR+3.3063{\ell}n\;GNP/Pop$$ To maintain optimum chestnut prices according to this model, chestnut production should be 133,000 ton for 1988, and 1,899,000 ton for 2010. 5. Optimum chestnut plantation area will be 4,000 ha in 1988, and thereafter total plantation area will be up to 57,400 ha in 2010.

• Journal of Gastric Cancer
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• v.23 no.1
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• pp.224-249
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• 2023

Gastric cancer is heterogeneous in morphology, biology, genomics, and treatment response. Alterations in human epidermal growth factor receptor 2 (HER2) overexpression, microsatellite instability (MSI) status, programmed death-ligand 1 (PD-L1) levels, and fibroblast growth factor receptor 2 (FGFR2) can be used as biomarkers. Since the combination of fluoropyrimidine/platinum plus trastuzumab that was investigated in the ToGA trial was approved as a standard of care in HER2-positive patients in 2010, no other agents showed efficacy in the first- (HELOISE, LOGiC, JACOB trials) and second- (TyTAN, GATSBY, T-ACT trials) line treatments. Despite the success in treating breast cancer, various anti-HER2 agents, including a monoclonal antibody (pertuzumab), an antibody-drug conjugate (ADC; trastuzumab emtansine [T-DM1]), and a small molecule (lapatinib) failed to translate into clinical benefits until the KEYNOTE-811 (first-line) and DESTINY-Gastri01 (≥second-line) trials were conducted. The incorporation of HER2-directed treatment with immune checkpoint inhibitors in the form of a monoclonal antibody or ADC is now approved as a standard treatment. Despite the promising results of new agents (engineered monoclonal antibodies, bi-specific antibodies, fusion proteins, and small molecules) in the early phase of development, the management of HER2-positive gastric cancer requires further optimization to achieve precision medicine with a chemotherapeutic backbone. Treatment resistance is a complex process that can be overcome using a combination of chemotherapy, targeted agents, and immune checkpoint inhibitors, including novel agents. HER2 status must be reassessed in patients undergoing anti-HER2 treatment with disease progression after the first-line treatment. As a general guideline, patients who need systemic treatment should receive chemotherapy plus targeted agents, anti-angiogenic agents, immune checkpoint inhibitors, or their combinations.

• Hanyang Medical Reviews
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• v.33 no.1
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• pp.10-16
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• 2013

Follicular helper T cells (Tfh) play a significant role in providing T cell help to B cells during the germinal center reaction, where somatic hypermutation, affinity maturation, isotype class switching, and the differentiation of memory B cells and long-lived plasma cells occur. Antigen-specific T cells with IL-6 and IL-21 upregulate CXCR5, which is required for the migration of T cells into B cell follicles, where these T cells mature into Tfh. The surface markers including PD-1, ICOS, and CD40L play a significant role in providing T cell help to B cells. The upregulation of transcription factor Bcl-6 induces the expression of CXCR5, which is an important factor for Tfh differentiation, by inhibiting the expression of other lineage-specific transcription factors such as T-bet, GATA3, and RORγt. Surprisingly, recent evidence suggests that CD4 T cells already committed to Th1, Th2, and Th17 cells obtain flexibility in their differentiation programs by downregulating T-bet, GATA3, and RORγt, upregulating Bcl-6 and thus convert into Tfh. Limiting the numbers of Tfh within germinal centers is important in the regulation of the autoantibody production that is central to autoimmune diseases. Recently, it was revealed that the germinal center reaction and the size of the Tfh population are also regulated by thymus-derived follicular regulatory T cells (Tfr) expressing CXCR5 and Foxp3. Dysregulation of Tfh appears to be a pathogenic cause of autoimmune disease suggesting that tight regulation of Tfh and germinal center reaction by Tfr is essential for maintaining immune tolerance. Therefore, the balance between Tfh and Tfr appears to be a critical peripheral tolerance mechanism that can inhibit autoimmune disorders.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.2
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• pp.99-104
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• 2015

The aim of this study is to develop a physiologically based pharmacokinetic (PBPK) model in intra-abdominal infected rats, and extrapolate it to human to predict moxifloxacin pharmacokinetics profiles in various tissues in intra-abdominal infected human. 12 male rats with intra- abdominal infections, induced by Escherichia coli, received a single dose of 40 mg/kg body weight of moxifloxacin. Blood plasma was collected at 5, 10, 20, 30, 60, 120, 240, 480, 1440 min after drug injection. A PBPK model was developed in rats and extrapolated to human using GastroPlus software. The predictions were assessed by comparing predictions and observations. In the plasma concentration versus time profile of moxifloxcinin rats, $C_{max}$ was $11.151{\mu}g/mL$ at 5 min after the intravenous injection and $t_{1/2}$ was 2.936 h. Plasma concentration and kinetics in human were predicted and compared with observed datas. Moxifloxacin penetrated and accumulated with high concentrations in redmarrow, lung, skin, heart, liver, kidney, spleen, muscle tissues in human with intra-abdominal infection. The predicted tissue to plasma concentration ratios in abdominal viscera were between 1.1 and 2.2. When rat plasma concentrations were known, extrapolation of a PBPK model was a method to predict drug pharmacokinetics and penetration in human. Moxifloxacin has a good penetration into liver, kidney, spleen, as well as other tissues in intra-abdominal infected human. Close monitoring are necessary when using moxifloxacin due to its high concentration distribution. This pathological model extrapolation may provide reference to the PK/PD study of antibacterial agents.

• Parasites, Hosts and Diseases
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• v.37 no.3
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• pp.181-188
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• 1999

We investigated the value of mitochondrial small subunit rRNA gene (mt SSU rDNA) PCR-RFLP as a taxonomic tool for Acanthamoeba isolates with close inter-relationships. Twenty-five isolates representing 20 species were included in the analysis. As in nuclear 18s rDNA analysis, two type strains (A. astronyxis and A. tubiashi) of morphological group 1 diverged earliest from the other strains, but the divergence between them was less than in 18s riboprinting. Acanthamoeba griffini of morhological group 2 branched between pathogenic (A. culbertsoni A-1 and A. healyi OC-3A) and nonpathogenic (A.palestinensis Reich, A. pustulosa GE-3a, A. royreba Oak Ridge, and A lenticulata PD2S) strains of morphological group 3. Among the remaining isolates of morphological group 2, the Chang strain had the identical mitochondrial riboprints as the type strain of A. hatchetti. AA2 and AA1, the type strains of A. divionensis and A. paradivionensis, respectively, had the identical riboprints as A. quina Vil3 and A. castellanii Ma. Although the branching orders of A. castellanii Neff, A. polyphaga P23, A. triangularis SH621, and A. lugdunensis L3a were different from those in 18S riboprinting analysis, the results obtained from this study generally coincided well with those from 18S riboprinting. Mitochondrial riboprinting may have an advantage over nuclear 18S rDNA riboprinting beacuse the mt SSU rDNAs do not seem to have introns that are found in the 18S genes of Acanthamoeba and that distort phylogenetic analyses.

• Journal of Periodontal and Implant Science
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• v.34 no.3
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• pp.489-498
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• 2004

Recent studies have demonstrated that human periodontal ligament cells express receptor activation of nuclear factor ${\kappa}B$ ligand (RANKL) which enhances the bone resorbing activity of osteoclasts differentiated from hematopoietic preosteoclasts. The purpose of this study is to determine the effects of p38 MAPK and JNK kinase upon regulating RANKL and OPG in response to $IL-1{\beta}$(l ng/ml) in rat periodontal ligament cells. Soluble RANKL was measured by immunoassay. The effects of p38 MAPK on RANKL and OPG expression was determined by RT-PCR. The results were as follows: 1. Periodontal ligament cells which stimulated by $IL-1{\beta}$ increased soluble RANKL synthesis by dose-dependent pattern. 2. p38 MAP kinase inhibitor (SB203580) showed regulation of soluble RANKL expression by dose-dependent manners. 3. p38 MAP kinase inhibitor (SB203580) regulated the expression of RANKL, but it dose regulate the expresseion of OPG. 4. JNK (c-jun $NH_2-terminal$ kinase) inhibitor (PD98059) did not regulate mRANKL and mOPG. These results suggested that p38 MAPK play a significant role in RANKL gene expression.

• 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.