• Biomolecules & Therapeutics
• /
• v.19 no.2
• /
• pp.255-260
• /
• 2011

The purpose of this study was to investigate the effect of ticlopidine on the pharmacokinetics of diltiazem and its active metabolite, desacetyldiltiazem, in rats. Pharmacokinetic parameters of diltiazem and desacetyldiltiazem were determined in rats after oral administration of diltiazem (15 $mg{\cdot}kg^{-1}$) with ticlopidine (3 or 9 $mg{\cdot}kg^{-1}$). The effects of ticlopidine on P-glycoprotein (P-gp) and cytochrome P450 (CYP) 3A4 activities were also evaluated. Ticlopidine inhibited CYP3A4 enzyme activity in a concentrationdependent manner with a 50% inhibition concentration ($IC_{50}$) of 35 ${\mu}M$. In addition, ticlopidine did not significantly enhance the cellular accumulation of rhodamine-123 in NCI/ADR-RES cells overexpressing P-gp. Compared with the control (given diltiazem alone), ticlopidine significantly altered the pharmacokinetic parameters of diltiazem. The peak concentration ($C_{max}$) and the area under the plasma concentration-time curve (AUC) of diltiazem were significantly (9 $mg{\cdot}kg^{-1}$, p<0.05) increased in the presence of ticlopidine. The AUC of diltiazem was increased by 1.44-fold in rats in the presence of ticlopidine (9 $mg{\cdot}kg^{-1}$). Consequently, the absolute bioavailability (A.B.) of diltiazem in the presence of ticlopidine (9.3-11.5%) was signifi cantly higher (9 $mg{\cdot}kg^{-1}$, p<0.05) than that in the control group (8.0%). Although ticlopidine significantly (p<0.05) increased the AUC of desacetyldiltiazem, the metabolite-parent AUC ratio (M.R.) in the presence of ticlopidine (9 $mg{\cdot}kg^{-1}$) was significantly decreased compared to that in the control group, implying that ticlopidine could effectively inhibit the metabolism of diltiazem. In conclusion, the concomitant use of ticlopidine significantly enhanced the oral bioavailability of diltiazem in rats by inhibiting CYP3A4-mediated metabolism in the intestine and/or liver rather than by inhibiting intestinal P-gp activity or renal elimination of diltiazem.

• Nutrition Research and Practice
• /
• v.13 no.2
• /
• pp.126-133
• /
• 2019

BACKGROUND/OBJECTIVES: The glycemic index (GI) is a measure of the postprandial glucose response (PPGR) to food items, and glycemic load (GL) is a measure of the PPGR to the diet. For those who need to maintain a healthy diet, it is beneficial to regulate appropriate levels of blood glucose. In reality, what influences the meal GI or GL depends on the macronutrient composition and the physical chemistry reactions in vivo. Thus, we investigated whether different macronutrients in a meal significantly affect the PPGR and the validity of calculated GI and GL values for mixed meals. SUBJECTS/METHODS: 12 healthy subjects (6 male, 6 female) were recruited at a campus setting, and subjects consumed a total of 6 test meals one by one, each morning between 8:00 and 8:30 am after 12 h of fasting. PPGR was measured after each consumed meal and serial finger pricks were performed at indicated times. Test meals included 1) 68 g oral glucose, 2) 210 g rice, 3) rice plus 170 g egg white (RE), 4) rice plus 200 g bean sprouts (RS), 5) rice plus 10 g oil (RO), and 6) rice plus, egg white, bean sprouts, and oil (RESO). The incremental area under the curve (iAUC) was calculated to assess the PPGR. Mixed meal GI and GL values were calculated based on the nutrients the subjects consumed in each of the test meals. RESULTS: The iAUC for all meals containing two macronutrients (RS, RO, or RE) were not significantly different from the rice iAUC, whereas, the RESO iAUC ($2,237.5{\pm}264.9$) was significantly lower (P < 0.05). The RESO meal's calculated GI and GL values were different from the actual GI and GL values measured from the study subjects (P < 0.05). CONCLUSIONS: The mixed meal containing three macronutrients (RESO) decreased the PPGR in healthy individuals, leading to significantly lower actual GI and GL values than those derived by nutrient-based calculations. Thus, consuming various macronutrient containing meals is beneficial in regulating PPGR.

• Journal of Korean Academy of Nursing
• /
• v.49 no.5
• /
• pp.575-585
• /
• 2019

Purpose: The purpose of this study was to develop predictive models for pressure ulcer incidence using electronic health record (EHR) data and to compare their predictive validity performance indicators with that of the Braden Scale used in the study hospital. Methods: A retrospective case-control study was conducted in a tertiary teaching hospital in Korea. Data of 202 pressure ulcer patients and 14,705 non-pressure ulcer patients admitted between January 2015 and May 2016 were extracted from the EHRs. Three predictive models for pressure ulcer incidence were developed using logistic regression, Cox proportional hazards regression, and decision tree modeling. The predictive validity performance indicators of the three models were compared with those of the Braden Scale. Results: The logistic regression model was most efficient with a high area under the receiver operating characteristics curve (AUC) estimate of 0.97, followed by the decision tree model (AUC 0.95), Cox proportional hazards regression model (AUC 0.95), and the Braden Scale (AUC 0.82). Decreased mobility was the most significant factor in the logistic regression and Cox proportional hazards models, and the endotracheal tube was the most important factor in the decision tree model. Conclusion: Predictive validity performance indicators of the Braden Scale were lower than those of the logistic regression, Cox proportional hazards regression, and decision tree models. The models developed in this study can be used to develop a clinical decision support system that automatically assesses risk for pressure ulcers to aid nurses.

• KIPS Transactions on Software and Data Engineering
• /
• v.11 no.3
• /
• pp.107-114
• /
• 2022

In this paper, we have enhanced the risk prediction of hypertension using the feature selection method in the Korean National Health and Nutrition Examination Survey (KNHANES) database of the Korea Centers for Disease Control and Prevention. The study identified various risk factors correlated with chronic hypertension. The paper is divided into three parts. Initially, the data preprocessing step of removes missing values, and performed z-transformation. The following is the feature selection (FS) step that used a factor analysis (FA) based on the feature selection method in the dataset, and feature importance (FI) and multicollinearity analysis (MC) were compared based on FS. Finally, in the predictive analysis stage, it was applied to detect and predict the risk of hypertension. In this study, we compare the accuracy, f-score, area under the ROC curve (AUC), and mean standard error (MSE) for each model of classification. As a result of the test, the proposed MC-FA-RF model achieved the highest accuracy of 80.12%, MSE of 0.106, f-score of 83.49%, and AUC of 85.96%, respectively. These results demonstrate that the proposed MC-FA-RF method for hypertension risk predictions is outperformed other methods.

• Korean Journal of Radiology
• /
• v.22 no.4
• /
• pp.535-546
• /
• 2021

Objective: To evaluate the feasibility of texture analysis on non-contrast-enhanced T1 maps of cardiac magnetic resonance (CMR) imaging for the diagnosis of myocardial injury in acute myocardial infarction (MI). Materials and Methods: This study included 68 patients (57 males and 11 females; mean age, 55.7 ± 10.5 years) with acute ST-segment-elevation MI who had undergone 3T CMR after a percutaneous coronary intervention. Forty patients of them also underwent a 6-month follow-up CMR. The CMR protocol included T2-weighted imaging, T1 mapping, rest first-pass perfusion, and late gadolinium enhancement. Radiomics features were extracted from the T1 maps using open-source software. Radiomics signatures were constructed with the selected strongest features to evaluate the myocardial injury severity and predict the recovery of left ventricular (LV) longitudinal systolic myocardial contractility. Results: A total of 1088 segments of the acute CMR images were analyzed; 103 (9.5%) segments showed microvascular obstruction (MVO), and 557 (51.2%) segments showed MI. A total of 640 segments were included in the 6-month follow-up analysis, of which 160 (25.0%) segments showed favorable recovery of LV longitudinal systolic myocardial contractility. Combined radiomics signature and T1 values resulted in a higher diagnostic performance for MVO compared to T1 values alone (area under the curve [AUC] in the training set; 0.88, 0.72, p = 0.031: AUC in the test set; 0.86, 0.71, p = 0.002). Combined radiomics signature and T1 values also provided a higher predictive value for LV longitudinal systolic myocardial contractility recovery compared to T1 values (AUC in the training set; 0.76, 0.55, p < 0.001: AUC in the test set; 0.77, 0.60, p < 0.001). Conclusion: The combination of radiomics of non-contrast-enhanced T1 mapping and T1 values could provide higher diagnostic accuracy for MVO. Radiomics also provides incremental value in the prediction of LV longitudinal systolic myocardial contractility at six months.

• Korean Journal of Radiology
• /
• v.21 no.9
• /
• pp.1045-1054
• /
• 2020

Objective: This study aimed to evaluate the diagnostic value of combining the quantitative parameters of shear wave elastography (SWE) and superb microvascular imaging (SMI) to breast ultrasound (US) to differentiate between benign and malignant breast masses. Materials and Methods: A total of 200 pathologically confirmed breast lesions in 192 patients were retrospectively reviewed using breast US with B-mode imaging, SWE, and SMI. Breast masses were assessed based on the breast imaging reporting and data system (BI-RADS) and quantitative parameters using the maximum elasticity (Emax) and ratio (Eratio) in SWE and the vascular index in SMI (SMI_VI). The area under the receiver operating characteristic curve (AUC) value, sensitivity, specificity, accuracy, negative predictive value, and positive predictive value of B-mode alone versus the combination of B-mode US with SWE or SMI of both parameters in differentiating between benign and malignant breast masses was compared, respectively. Hypothetical performances of selective downgrading of BI-RADS category 4a (set 1) and both upgrading of category 3 and downgrading of category 4a (set 2) were calculated. Results: Emax with a cutoff value of 86.45 kPa had the highest AUC value compared to Eratio of 3.57 or SMI_VI of 3.35%. In set 1, the combination of B-mode with Emax or SMI_VI had a significantly higher AUC value (0.829 and 0.778, respectively) than B-mode alone (0.719) (p < 0.001 and p = 0.047, respectively). B-mode US with the addition of Emax, Eratio, and SMI_VI had the best diagnostic performance of AUC value (0.849). The accuracy and specificity increased significantly from 68.0% to 84.0% (p < 0.001) and from 46.1% to 79.1% (p < 0.001), respectively, and the sensitivity decreased from 97.6% to 90.6% without statistical loss (p = 0.199). Conclusion: Combining all quantitative values of SWE and SMI with B-mode US improved the diagnostic performance in differentiating between benign and malignant breast lesions.

• Archives of Pharmacal Research
• /
• v.18 no.5
• /
• pp.340-345
• /
• 1995

A nebumetone tablet in development $(Navuton^R)$ was tested for its bioequivalence to the erference tablet $(Uniton^R)$. Seventeen healthy Korean male subjects participated in this study. Each subject received a 1-g dose of nabumetone (2tables each) in an unbalanced, randomized, two-way crossover investigation. Serum concentrations of 6-methoxy-2-na-phthylacetic acid (6-MNA), a major metabolite of nebumetone, were measured over 120 hr interval by a high-performance liquid chromatography. The maximum serum concentration $(C_{max})$ and time to reach the maximum concentration$(T_{max})$ were read directly, but area under the serum concentration time curve from time 0 to 120 hr (AUC) and mean residence time serum curves showed multiple peaks of 6-MNA in most subjects, and the $C_{max}$ and $T_{max}$ were read from the highest serum peaks. calculated bioavailability parameters for test and reference tablets were 148.6 : 1377.9 $\mug \cdot hr/ml$ for AUC; 25.2:23.1 $\mu/ml$ for $C_{max}$; 11.8:16.4 hr for $T_{max}$, and 42.6 : 43.8 hr for MRT, respectively. The paired t-test revealed no significant differences in all the parameters between the two tablets. Analysis ofl variance (ANOVA) revealed no significant differences between groups and formulations in all the parameters ($C_{max}$ and $T_{max}$, AUC and MRT) indicating the crossover design of the experiment was properly performed. But significant differences (p<0.05) between subject/groups and periods were found for all the parameters indicating substantial intersubject and interperiodic variations for these parameters.

• Korean Journal of Clinical Pharmacy
• /
• v.10 no.1
• /
• pp.25-29
• /
• 2000

Bioequivalence of cisapride-containing $Cisaplus^{(R)}$ tablets (Daewoong Co.) to reference $Prepulsid^{(R)}$ tablets (Janssen Co.) was evaluated according to the guidelines of Korea Food and Drug Administration (KFDA). Sixteen healthy volunteers were divided randomly into two groups and administered orally at a cisapride dose of 10 mg in a $2\times2$ crossover design. There was a 1-week washout period between the treatments. Blood samples were taken at predetermined time intervals for 48 hr and the plasma cisapride concentrations were determined by an HPLC with UV detector. The area under the plasma drug concentration-time curve (AUC) was caltulated from time zero to the last sampling time by a linear trapezoidal method. The maximum observed plasma drug concentration ($C_{max}$) and the time to $C_{max}\;(T_{max})$ were estimated directly from the drug concentration-time data. Analysis of variance (ANOVA) showed that the apparent differences for AUC, $C_{max}\;and\;T_{max}$ were $-7.52\%,\;-8.91\%\;and\;-15.55\%$, respectively. The minimum detectable differences for AUC, $C_{max}\;and\;T_{max}$ between formulations were $14.52\%,\;11.57\%\;and\;28.00\%$ respectively, at $\alpha=0.05\;and\;1-\beta=0.8\;levels.\;The\;90\%$ confidence intervals for AUC, $C_{max}\;and\;T_{max}\;were\;-16.00\sim0.97\%,\;-15.67\sim-2.15\%\;and\;-31.88\%\sim0.84\%$, respectively. These results satisfy the bioequivalence criteria of KFDA guidelines, indicating that the two formulations of cisapride are bioequivalent.

• Journal of the Korea Convergence Society
• /
• v.13 no.3
• /
• pp.33-41
• /
• 2022

In this article, we proposed to predict natural gas (NG) leakage levels through feature selection based on a factor analysis (FA) of the integrating the Korean Meteorological Agency data and natural gas leakage data for considering complex factors. The paper has been divided into three modules. First, we filled missing data based on the linear interpolation method on the integrated data set, and selected essential features using FA with OrdinalEncoder (OE)-based normalization. The dataset is labeled by K-means clustering. The final module uses four algorithms, K-nearest neighbors (KNN), decision tree (DT), random forest (RF), Naive Bayes (NB), to predict gas leakage levels. The proposed method is evaluated by the accuracy, area under the ROC curve (AUC), and mean standard error (MSE). The test results indicate that the OrdinalEncoder-Factor analysis (OE-F)-based classification method has improved successfully. Moreover, OE-F-based KNN (OE-F-KNN) showed the best performance by giving 95.20% accuracy, an AUC of 96.13%, and an MSE of 0.031.

• Korean Journal of Radiology
• /
• v.22 no.8
• /
• pp.1369-1378
• /
• 2021

Objective: Few attempts have been made to investigate the prognostic value of dynamic contrast-enhanced (DCE) MRI or dynamic susceptibility contrast (DSC) MRI of non-enhancing, T2-high-signal-intensity (T2-HSI) lesions of glioblastoma multiforme (GBM) in newly diagnosed patients. This study aimed to investigate the prognostic values of DCE MRI and DSC MRI parameters from non-enhancing, T2-HSI lesions of GBM. Materials and Methods: A total of 76 patients with GBM who underwent preoperative DCE MRI and DSC MRI and standard treatment were retrospectively included. Six months after surgery, the patients were categorized into early progression (n = 15) and non-early progression (n = 61) groups. We extracted and analyzed the permeability and perfusion parameters of both modalities for the non-enhancing, T2-HSI lesions of the tumors. The optimal percentiles of the respective parameters obtained from cumulative histograms were determined using receiver operating characteristic (ROC) curve and univariable Cox regression analyses. The results were compared using multivariable Cox proportional hazards regression analysis of progression-free survival. Results: The 95th percentile value (PV) of Ktrans, mean Ktrans, and median Ve were significant predictors of early progression as identified by the ROC curve analysis (area under the ROC curve [AUC] = 0.704, p = 0.005; AUC = 0.684, p = 0.021; and AUC = 0.670, p = 0.0325, respectively). Univariable Cox regression analysis of the above three parametric values showed that the 95th PV of Ktrans and the mean Ktrans were significant predictors of early progression (hazard ratio [HR] = 1.06, p = 0.009; HR = 1.25, p = 0.017, respectively). Multivariable Cox regression analysis, which also incorporated clinical parameters, revealed that the 95th PV of Ktrans was the sole significant independent predictor of early progression (HR = 1.062, p < 0.009). Conclusion: The 95th PV of Ktrans from the non-enhancing, T2-HSI lesions of GBM is a potential prognostic marker for disease progression.