• Biomolecules & Therapeutics
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• v.6 no.2
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• pp.219-224
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• 1998

The bioequivalence of two clarithromvcin products was evaluated with 16 normal male volunteers (age 23-28 yr, body weight 57.5-75.517g) following single oral dose. Test product was ReYon Clarithromycin tablets (ReYon Pharm. Corp., Korea) and reference product was Klarici $d_{R}$ tablets (Abbott Korea). Both products contain 250 mg of clarithromucin. One tablet of the test or the reference product was administered to the volunteers, respectively, by randomized two period cross-over study (2$\times$2 Latin square method). The determination of clarithromycin was accomplished using a modified agar well diffusion bioassay. As a result of the assay validation, the quantification of clarithromycin in human serum by this technique was possible down to 0.03$\mu$g/ml using 100$\mu$l of serum. The coefficient of variation (C.V.) was less than 10%. Average drug concentrations at each sampling time and pharmacokinetic parameters calculated were not significantly different between two products P>0.05); the area under the curve to last sampling time (24 hr) (AU $Co_{24hr}$ (8.10$\pm$ 1.26 vs 8.22$\pm$ 1.627g . hr/ml), AUC from time zero to infinite (AU $Co_{\infty}$) (8.61 $\pm$ 1.28 vs 8.84$\pm$ 1.71 $\mu$g . hr/ml), maximum plasma concentration ( $C_{msx}$) (0.87$\pm$0.22 vs 0.88$\pm$0.19 $\mu$g/ml) and time to maximum plasma concentration ( $T_{max}$) (2.69 $\pm$0.48 vs 2.56$\pm$ 0.51 hr). The differences of mean AU $Co_{24h}$, $C_{msx}$ and $T_{msx}$ between the two products (1.44, 1.39, and 4.65%, respectively) were less than 20%. The power (1-$\beta$) and treatment difference ($\Delta$) for AU $Co_{24hr}$, and $C_{max}$ were more than 0.8 and less than 0.2, respectivly. Although the power for $T_{max}$ was under 0.8, $T_{max}$. of the two products was not significantly different each other (p>0.05). These results suggest that the bioavailability of ReYon Clarithromycin tablets is not significantly different from that of Klarici $d_{R}$ tablets. Therefore, two products are bioequivalent based on the current results. results.sults.sults.s.s.s.s.s.s.s.

• Korean Journal of Agricultural and Forest Meteorology
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• v.22 no.2
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• pp.47-56
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• 2020

Decline of pine forests happens in Korea due to various disturbances such as insect pests, forest fires and extreme climate, which may further continue with ongoing climate change. For conserving and reestablishing pine forests, understanding climate-induced future shifts of pine tree distribution is a critical concern. This study predicts future geographical distribution of Pinus densiflora, using Maximum Entropy Model (MaxEnt). Input data of the model are locations of pine tree stands and their environmental variables such as climate were prepared for the model inputs. Alternative future projections for P. densiflora distribution were conducted with RCP 4.5 and RCP 8.5 climate change scenarios. As results, the future distribution of P. densiflora steadily decreased under both scenarios. In the case of RCP 8.5, the areal reductions amounted to 11.1% and 18.7% in 2050s and 2070s, respectively. In 2070s, P. densiflora mainly remained in Kangwon and Gyeongsang Provinces. Changes in temperature seasonality and warming winter temperature contributed primarily for the decline of P. densiflora., in which altitude also exerted a critical role in determining its future distribution geographic vulnerability. The results of this study highlighted the temporal and spatial contexts of P. densiflora decline in Korea that provides useful ecological information for developing sound management practices of pine forests.

• Journal of Gastric Cancer
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• v.9 no.4
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• pp.177-185
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• 2009

Purpose: Preoperative clinical staging of gastric cancer is very important for determining the treatment plans and predicting the prognosis. The previous reports regarding the accuracy of computed tomography or endoscopic ultrasound for the preoperative staging of gastric cancer have shown various outcomes. We analyzed the diagnostic performance of CT and EUS, which are important staging tools for the staging of TN gastric cancer. Materials and Methods: We retrospectively analyzed 1,174 patients who underwent gastrectomy for gastric cancer at Seoul National University Bundang Hostpital from May, 2003 to December, 2007. We derived the Kappa value to examine the agreement of the preoperative staging obtained from CT and EUS with the pathological staging. Results: The mean age of the 1,174 patients was $59.31{\pm}11.98$ years. Six hundred thirty seven patients had early gastric cancer and 536 had advanced gastric cancer. The diagnostic performance between CT and EUS for the T staging showed no significant difference between CT and EUS for the kappa values. The kappa values showed moderate agreement at 0.4039 (P=0.021) and 0.4201 (P=0.026), respectively. This suggests that there is no difference between the two examinations for the overall T staging. Analysis of the discrimination of mucosal and submucosal lesions with EUS showed an accuracy of 58.92% and a Kappa value of 0.206 (P<0.001), suggesting fair agreement and a lower diagnostic performance than expected. To differentiate lesions with stages higher than or equal to T2 or T3 from the lesion with stages lower than T2 or T3, respectively, adoption of the higher stage from the CT staging or the EUS staging showed a larger AUC of 0.84 than that from either stage alone. The CT-derived node stage had the higher diagnostic performance (68.55%) than that of the EUS-derived node stage (60.82%) for the node staging. Conclusion: The CT-derived stage and EUS-derived stage showed comparable results for determining the T stage of gastric cancer. Yet the higher stage of the two stages from CT and EUS most accurately discriminated between those lesions with stages higher than T2 and those lesions with stages lower than T2.

• Korean Journal of Psychosomatic Medicine
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• v.27 no.2
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• pp.101-110
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• 2019

Objectives : It is not clear which clinical variables are most closely associated with delirium in the Intensive Care Unit (ICU). By comparing clinical data of ICU delirium and non-delirium patients, we sought to identify variables that most effectively differentiate delirium from non-delirium. Methods : Medical records of 6,386 ICU patients were reviewed. Random Subset Feature Selection and Principal Component Analysis were utilized to select a set of clinical variables with the highest discriminatory capacity. Statistical analyses were employed to determine the separation capacity of two models-one using just the selected few clinical variables and the other using all clinical variables associated with delirium. Results : There was a significant difference between delirium and non-delirium individuals across 32 clinical variables. Richmond Agitation Sedation Scale (RASS), urinary catheterization, vascular catheterization, Hamilton Anxiety Rating Scale (HAM-A), Blood urea nitrogen, and Acute Physiology and Chronic Health Examination II most effectively differentiated delirium from non-delirium. Multivariable logistic regression analysis showed that, with the exception of vascular catheterization, these clinical variables were independent risk factors associated with delirium. Separation capacity of the logistic regression model using just 6 clinical variables was measured with Receiver Operating Characteristic curve, with Area Under the Curve (AUC) of 0.818. Same analyses were performed using all 32 clinical variables;the AUC was 0.881, denoting a very high separation capacity. Conclusions : The six aforementioned variables most effectively separate delirium from non-delirium. This highlights the importance of close monitoring of patients who received invasive medical procedures and were rated with very low RASS and HAM-A scores.

• Journal of the Korean Society of Food Science and Nutrition
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• v.44 no.5
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• pp.752-760
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• 2015

Effects of maltogenic amylase on textural properties of dough and quality characteristics of white pan bread were investigated. White pan bread was prepared with four different levels of maltogenic amylase contents (M-1: 0.048 U/g, M-2: 0.060 U/g, M-3: 0.072 U/g, M-4: 0.084 U/g). The setback by amylograph for the control was $480.0{\pm}12.25$ Brabender Unit (B.U.) while M-4 showed the a setback of $215.0{\pm}5.00B.U.$ The absorption, mixing tolerance index, and stability by farinogram were not significantly different (P>0.05) for across all treatments. The area under the curve (135 min) by extensogram was higher than all samples. The texture profile analysis results showed that there was significant decreasing in hardness for the maltogenic amylase infused bread (P<0.05). M-3 and M-4 showed higher springiness and cohesiveness but lower hardness than control over 1 to 3 days, indicating possibly extended shelf-life. Imaging scan showed that air cell size less than $0.4mm^2$ for the control and M-4 were at rates of 94.90% and 95.70%, respectively. For sensory evaluation, M-3 and M-4 showed higher intensities than the control for taste, flavor, texture, mouthfeel, and moistness quality. These results imply that the quality of white pan bread could be improved by adding maltogenic amylase without the use of chemical additives.

• Biomolecules & Therapeutics
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• v.18 no.4
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• pp.469-476
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• 2010

This study was to investigate the effect of apigenin on the bioavailability of paclitaxel after oral and intravenous administration in rats. The effect of apigenin on P-glycoprotein (P-gp), cytochrome P450 (CYP)3A4 activity was evaluated. The pharmacokinetic parameters of paclitaxel were determined in rats after oral (40 mg/kg) or intravenous (5 mg/kg) administration of paclitaxel with apigenin (0.4, 2 and 8 mg/kg) to rats. Apigenin inhibited CYP3A4 activity with 50% inhibition concentration ($IC_{50}$) of 1.8 ${\mu}M$. In addition, apigenin significantly inhibited P-gp activity. Compared to the control group, apigenin significantly increased the area under the plasma concentration-time curve (AUC, p<0.05 by 2 mg/kg, 59.0% higher; p<0.01 by 8 mg/kg, 87% higher) of oral paclitaxel. Apigenin also significantly (p<0.05 by 2 mg/kg, 37.2% higher; p<0.01 by 8 mg/kg, 59.3% higher) increased the peak plasma concentration ($C_{max}$) of oral paclitaxel. Apigenin significantly increased the terminal half-life ($t_{1/2}$, p<0.05 by 8 mg/kg, 34.5%) of oral paclitaxel. Consequently, the absolute bioavailability (A.B.) of paclitaxel was significantly (p<0.05 by 2 mg/kg, p<0.01 by 8 mg/kg) increased by apigenin compared to that in the control group, and the relative bioavailability (R.B.) of oral paclitaxel was increased by 1.14- to 1.87-fold. The pharmacokinetics of intravenous paclitaxel were not affected by the concurrent use of apigenin in contrast to the oral administration of paclitaxel. Accordingly, the enhanced oral bioavailability by apigenin may be mainly due to increased intestinal absorption caused via P-gp inhibition by apigenin rather than to reduced renal and hepatic elimination of paclitaxel. The increase in the oral bioavailability might be mainly attributed to enhanced absorption in the gastrointestinal tract via the inhibition of P-gp and reduced first-pass metabolism of paclitaxel via the inhibition of the CYP3A subfamily in the small intestine and/or in the liver by apigenin. It appears that the development of oral paclitaxel preparations as a combination therapy is possible, which will be more convenient than the i.v. dosage form.

• Animal Bioscience
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• v.36 no.9
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• pp.1336-1349
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• 2023

Objective: The study was conducted to screen differentially expressed miRNAs in sows at early pregnancy by high-throughput sequencing and explore its mechanism of action on embryo implantation. Methods: The blood serum of pregnant and non-pregnant Landrace×Yorkshire sows were collected 14 days after artificial insemination, and exosomal miRNAs were purified for high throughput miRNA sequencing. The expression patterns of 10 differentially expressed (DE) miRNAs were validated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The qRT-PCR quantified the abundance of serum exosomal miR-192 in pregnant and control sows, and the diagnostic power was assessed by receiver operating characteristic (ROC) analysis. The target genes of DE miRNAs were predicted with bioinformatics software, and the functional and pathway enrichment analysis was performed on gene ontology and the Kyoto encyclopedia of genes and genomes terms. Furthermore, a luciferase reporter system was used to identify the target relation between miR-192 and integrin alpha 4 (ITGA4), a gene influencing embryo implantation in pigs. Finally, the expression levels of miRNAs and the target gene ITGA4 were analyzed by qRT-PCR, and western blot, with the proliferation of BeWo cells detected by cell counting kit-8 (CCK-8). Results: A total of 221 known miRNAs were detected in the libraries of the pregnant and non-pregnant sows, of which 55 were up-regulated and 67 were down-regulated in the pregnant individuals compared with the non-pregnant controls. From these, the expression patterns of 10 DE miRNAs were validated. The qRT-PCR analysis further confirmed a significantly higher expression of miR-192 in the serum exosomes extracted from pregnant sows, when compared to controls. The ROC analysis revealed that miR-192 provided excellent diagnostic accuracy for pregnancy (area under the ROC curve [AUC]=0.843; p>0.001). The dual-luciferase reporter assay indicated that miR-192 directly targeted ITGA4. The protein expression of ITGA4 was reduced in cells that overexpressed miR-192. Overexpression of miR-192 resulted in the decreased proliferation of BeWo cells and regulated the expression of cell cycle-related genes. Conclusion: Serum exosomal miR-192 could serve as a potential biomarker for early pregnancy in pigs. miR-192 targeted ITGA4 gene directly, and miR-192 can regulate cellular proliferation.

• Nutrition Research and Practice
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• v.15 no.1
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• pp.54-65
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• 2021

BACKGROUND/OBJECTIVES: This study aimed to develop healthy, appetizing high-protein snacks with enhanced isolated soy protein for diabetic patients and determine the blood glucose and insulin response after being consumed by these patients. MATERIALS/METHODS: Thirty adult patients aged between 30 and 75 years, with a ≤ 10-year history of type 2 diabetes and hemoglobin A1c of < 7.5%, were enrolled in this study. They made 3 clinical visits at one-week intervals. The control group consumed 50 g carbohydrates (white bread), whereas the test groups consumed high-protein grain (HP_G) or high-protein chocolate (HP_C) after an 8-hrs fast. Blood (2 ㎤) was drawn at 15, 30, 45, 60, 90, and 120 min before and after consumption to analyze the blood glucose and insulin concentrations. RESULTS: Compared to the commercial snacks, the developed high-protein snacks had below-average calorie, carbohydrate, and fat content and a 2.5-fold higher protein content. In diabetic patients who consumed these snacks, the postprandial blood glucose increased between 15 min and 2 h after consumption, which was significantly slower than the time taken for the blood glucose to increase in the patients who consumed the control food product (P < 0.001). Insulin secretion was significantly lower at 45 min after consumption (P < 0.05), showing that the high-protein snacks did not increase the blood glucose levels rapidly. The incremental area under the curve (iAUC), which indicated the degree of blood sugar and insulin elevation after food intake, was higher in the control group than the groups given the 2 developed snacks (P < 0.001), and there was no significant difference in insulin secretion. CONCLUSIONS: The results of the postprandial blood glucose and insulin response suggest that high-protein snacks are potential convenient sources of high-quality protein and serve as a healthier alternative for patients with type 2 diabetes, who may have limited snack product choices. Such snacks may also provide balanced nutrition to pre-diabetic and obese individuals.

• Journal of Ginseng Research
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• v.43 no.3
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• pp.460-474
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• 2019

Background: Ginsenoside compound K (CK) is a promising drug candidate for rheumatoid arthritis. This study examined the impact of polymorphisms in NR1I2, adenosine triphosphate-binding cassette (ABC) transporter genes on the pharmacokinetics of CK in healthy Chinese individuals. Methods: Forty-two targeted variants in seven genes were genotyped in 54 participants using Sequenom MassARRAY system to investigate their association with major pharmacokinetic parameters of CK and its metabolite 20(S)-protopanaxadiol (PPD). Subsequently, molecular docking was simulated using the AutoDock Vina program. Results: ABCC4 rs1751034 TT and rs1189437 TT were associated with increased exposure of CK and decreased exposure of 20(S)-PPD, whereas CFTR rs4148688 heterozygous carriers had the lowest maximum concentration ($C_{max}$) of CK. The area under the curve from zero to the time of the last quantifiable concentration ($AUC_{last}$) of CK was decreased in NR1I2 rs1464602 and rs2472682 homozygous carriers, while $C_{max}$ was significantly reduced only in rs2472682. ABCC4 rs1151471 and CFTR rs2283054 influenced the pharmacokinetics of 20(S)-PPD. In addition, several variations in ABCC2, ABCC4, CFTR, and NR1I2 had minor effects on the pharmacokinetics of CK. Quality of the best homology model of multidrug resistance protein 4 (MRP4) was assessed, and the ligand interaction plot showed the mode of interaction of CK with different MRP4 residues. Conlusion: ABCC4 rs1751034 and rs1189437 affected the pharmacokinetics of both CK and 20(S)-PPD. NR1I2 rs1464602 and rs2472682 were only associated with the pharmacokinetics of CK. Thus, these hereditary variances could partly explain the interindividual differences in the pharmacokinetics of CK.

• Korean Journal of Veterinary Research
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• v.46 no.4
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• pp.323-326
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• 2006

Suaeda (S.) asparagoides $M_{IQ}$, one of the halophyte groups, has been used as a folk remedy for digestive disturbances in Korea. However, its pharmacological activity on gastrointestinal motility has not been reported yet. In this study, the effects of this halophyte extracts with various solvent fractions (ethanol, hexane, chloroform, ethyl acetate, butanol, and water) on mice ileal spontaneous motility was examined. All solvent fractions at the concentration of $100{\mu}g/ml$ showed inhibitory actions on spontaneous motility of ileum with the potency order of water > 70% ethanol > hexane ${\gg}$ chloroform ${\geq}$ butanol ${\geq}$ ethyl acetate, respectively. In addition, the water fraction of extracts from S. asparagoides $M_{IQ}$ (WFSA) dose-dependently ($1-100{\mu}g/ml$) inhibited the amplitude of spontaneous phasic contraction and area under the contractile curve (AUC). The inhibitory effect of water fraction at the concentration of $10{\mu}g/ml$ was not affected by tetrodotoxin (TTX), $Na^+$ channel blocker ($1{\mu}M$), and $N^w$-nitro-L-arginine Methyl Ester (L-NAME), nitric oxide synthase inhibitor ($100{\mu}M$). However, cyclopiazonic acid (CPA, $10{\mu}M$), inhibitor of sarcoplasmic reticulum $Ca^{2+}$-ATPase, almost blocked the inhibitory effects of WFSA ($10{\mu}g/ml$) on the spontaneous phasic contraction of mouse ileum. But, CPA did not inhibit the lowering basal tone effects of WFSA. The result of this study showed that various extracts of S. asparagoides $M_{IQ}$ induce inhibitory effects on spontaneous contraction of mice ileal segments. More over, the polar solvent fractions were shown to be more potent than non-polar solvent fractions. The effects of S. asparagoides $M_{IQ}$ extracts are not mediated by nerve or nitric oxide. The inhibitory effects of WFSA at least partially mediated by sarcoplasmic reticulum $Ca^{2+}$-ATPase. However, further study is required to determine the exact pharmacological mechanisms of this halophyte on its gastrointestinal motility inhibitory effects.