• Title/Summary/Keyword: PK method

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Compatibility Study between Physiologically Based Pharmacokinetic (PBPK) and Compartmental PK Model Using Lumping Method: Application to the Voriconazole Case (럼핑법을 이용한 생리학 기반 약물동태모델 및 구획화 약물동태모델 상호 호환 연구: 보리코나졸 적용 연구)

  • Ryu, Hyo-jeong;Kang, Won-ho;Chae, Jung-woo;Yun, Hwi-yeol
    • Korean Journal of Clinical Pharmacy
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    • v.31 no.2
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    • pp.125-135
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    • 2021
  • Background: Generally, pharmacokinetics (PK) models could be stratified into two models. The compartment PK model uses the concept of simple compartmentalization to describe complex bodies, and the physiologically based pharmacokinetic (PBPK) model describes the body using multi-compartment networking. Notwithstanding sharing a theoretical background in both models, there was still a lack of knowledge to enhance compatibility in both models. Objective: This study aimed to evaluate the compatibility among PBPK, lumping model and compartment PK model with voriconazole PK case study. Methods: The number of compartments and blood flow on each tissue in the PBPK model were modified using the lumping method, considering physiological similarities. The concentration-time profiles and area under the concentration-time curve (AUC) parameters were simulated at each model, assuming taken voriconazole oral 400 mg single dose. After that, those mentioned PK parameters were compared. Results: The PK profiles and parameters of voriconazole in the three models were similar that proves their compatibility. The AUC of central compartment in the PBPK and lumping model was within a 2-fold range compared to those in the 2- compartment model. The AUC of non-eliminating tissues compartment in the PBPK model was similar to those in the lumping model. Conclusion: Regarding the compatibility of the three PK models, the utilization of the lumping method was confirmed by suggesting its reliable PK parameters with PBPK and compartment PK models. Further case studies are recommended to confirm our findings.

A Study on Pk(Probability of Kill) Calculation Method of the Direct Fire Weapon System using ANN (인공신경망을 적용한 직사화기 무기체계의 살상확률(Pk) 산출방법론 연구)

  • Jang, Young Cheon;Han, Hyun Jin;Lee, Ki Teak;Song, Mi Jin;Lee, Hwi Yeong;Kim, Jong Heon
    • Journal of the Korea Society for Simulation
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    • v.28 no.1
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    • pp.99-107
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    • 2019
  • Until now it has had the limitation of the target in the US JMEM to calculate the Pk with the existing method by our study. In this study, we focused on deriving a method to calculate the Pk of the actual targets except JMEM targets using ANN. We study the initial predictive model of ANN(Artificial Neural Network) from the targets data of the specification and the vulnerable area in the US JMEM(Joint Munitions Effectiveness Manuals), and calculate the actual targets vulnerable area by using this method. Finally, we propose a method to calculate the Pk by applying those data to the existing method of us.

Simultaneous Determination of Isoegomaketone and Perillaketone in Perilla frutescens (L.) Britton Leaves by HPLC-DAD (HPLC-DAD를 이용한 차조기 잎의 Isoegomaketone 및 Perillaketone의 동시분석법 확립)

  • Nam, Bo Mi;Lee, Seung Young;Kim, Jin-Baek;Kang, Si-Yong;Jin, Chang Hyun
    • Korean Journal of Pharmacognosy
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    • v.47 no.1
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    • pp.79-83
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    • 2016
  • This study developed an HPLC analysis method for the determination of isoegomaketone (IK) and perillaketone (PK) in Perilla frutescens (L.) Britton leaves. P. frutescens ethanol extract was optimized through an HPLC analysis using a C18 column ($250{\times}4.6mml$, D, $S-5{\mu}m$, 12 nm) with gradient elution of water and acetonitrile as the mobile phase at a flow rate of 1 mL/min and a UV detection wavelength of 254 nm. The results of this method showed linearity in the calibration curve at a coefficient of correlation ($R^2$) of IK 0.9995, PK 0.9998. The limits of detection (LOD) for IK and PK were $0.234{\mu}g/mL$ and $0.952{\mu}g/mL$. The limits of quantification (LOQ) for IK and PK were $0.017{\mu}g/mL$ and $0.043{\mu}g/mL$. The inter-day precision RSDs of IK and PK in the P. frutescens were 1.25 to 2.69% and 0.36 to 1.10%, respectively, and the intra-day precision RSDs of IK and PK were 0.96 to 2.51% and 0.90 to 1.93%, respectively. The accuracies of IK and PK were 96.31 to 97.92% and 101.26 to 105.14%. In conclusion, this method was applied successfully to the detection of IK and PK in P. frutescens.

A Convenient Radiolabeling of [$^{11}$C](R)-PK11195 Using Loop Method in Automatic Synthesis Module ($^{11}$C 표지 자동합성장치에서 루프법을 이용한 ($^{11}$C)(R)-PK11195의 간편한 합성법)

  • Lee, Hak-Jeong;Jeong, Jae-Min;Lee, Yun-Sang;Kim, Hyung-Woo;Choi, Jae-Yeon;Lee, Dong-Soo;Chung, June-Key;Lee, Myung-Chul
    • Nuclear Medicine and Molecular Imaging
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    • v.43 no.4
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    • pp.337-343
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    • 2009
  • Purpose: ((R)-1-(2-chlorophenyl)-N-1-[$^{11}$C]methyl-N(1-propyl)-3-isoquinoline carboxamide ((R)-PK11195) is a specific ligand for the peripheral type benzodiazepine receptor and a marker of activated microglia, used to measure inflammation in neurologic disorders. We report here that a direct and simple radiosynthesis of [$^{11}$C](R)-PK11195 in mild condition using NaH suspension in DMF and one-step loop method. Materials and Methods: (R)-N-Desmethyl-PK11195 (1 mg) in DMSO (0.1 mL) and NaH suspension in DMF (0.1 mL) were injected into a semi-prep HPLC loop. [$^{11}$C]methyl iodide was passed through HPLC loop at room temperature. Purification was performed using semi-preparative HPLC. Aliquots eluted at 11.3 min were collected and analyzed by analytical HPLC and mass spectrometer. Results: The labeling efficiency of [$^{11}$C](R)-PK11195 was 71.8$\pm$8.5%. The specific activity was 11.8:$\pm$6.4 GBq/$\mu$mol and radiochemical purity was higher than 99.2%. The mass spectrum of the product eluted at 11.3 min showed m/z peaks at 353.1 (M+1), indicating the mass and structure of (R)-PK11195. Conclusion: By the one-step loop method with the [$^{11}$C]CH3l automated synthesis module, [$^{11}C$](R)-PK11195 could be easily prepared in high radiochemical yield using NaH suspension in DMF.

Increase of L-type Calcium Current by cGMP-dependent Protein Kinase Regulates in Rabbit Ventricular Myocytes

  • Han, Jin;Kim, Na-Ri;Kim, Eui-Yong;Ho, Won-Kyung;Earm, Yung-E;Kim, Han-Kyoun
    • The Korean Journal of Physiology and Pharmacology
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    • v.2 no.6
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    • pp.733-742
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    • 1998
  • Background: We have previously reported that not only cGMP but also 8-Br-cGMP or 8-pCPT-cGMP, specific and potent stimulators of cGMP-dependent protein kinase (cGMP-PK), increased basal L-type calcium current $(I_{Ca})$ in rabbit ventricular myocytes. Our findings in rabbit ventricular myocytes were entirely different from the earlier findings in different species, suggesting that the activation of cGMP-PK is involved in the facilitation of $I_{Ca}}$ by cGMP. However, there is no direct evidence that cGMP-PK can stimulate $I_{Ca}}$ in rabbit ventricular myocytes. In this report, we focused on the direct effect of cGMP-PK on $I_{Ca}}$ in rabbit ventricular myocytes. Methods and Results: We isolated single ventricular myocytes of rabbit hearts by using enzymatic dissociation. Regulation of $I_{Ca}}$ by cGMP-PK was investigated in rabbit ventricular myocytes using whole-cell voltage clamp method. $I_{Ca}}$ was elicited by a depolarizing pulse to +10 mV from a holding potential of -40 mV. Extracellular 8-(4-Chlorophenylthio)-guanosine-3',5'-cyclic monophosphate (8-pCPT-cGMP), potent stimulator of cGMP-dependent protein kinase (cGMP-PK), increased basal $I_{Ca}}$. cGMP-PK also increased basal $I_{Ca}}$. The stimulation of basal $I_{Ca}}$ by cGMP-PK required both 8-Br-cGMP in low concentration and intracellular ATP to be present. The stimulation of basal $I_{Ca}}$ by cGMP-PK was blocked by heat inactivation of the cGMP-PK and by bath application of 8-(4-chlorophenylthio)-guanosine-3',5'-cyclic monophosphate, Rp-isomer (Rp-pCPT-cGMP), a phosphodiesterase-resistant cGMP-PK inhibitor. When $I_{Ca}}$ was increased by internal application of cGMP-PK, IBMX resulted in an additional stimulation of $I_{Ca}}$. In the presence of cGMP-PK, already increased $I_{Ca}}$ was potentiated by bath application of isoprenaline or forskolin or intracellular application of cAMP. Conclusions: We present evidence that cGMP-PK stimulated basal $I_{Ca}}$ by a direct phosphorylation of L-type calcium channel or associated regulatory protein in rabbit ventricular myocytes.

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Using Highly Secure Data Encryption Method for Text File Cryptography

  • Abu-Faraj, Mua'ad M.;Alqadi, Ziad A.
    • International Journal of Computer Science & Network Security
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    • v.21 no.12
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    • pp.53-60
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    • 2021
  • Many standard methods are used for secret text files and secrete short messages cryptography, these methods are efficient when the text to be encrypted is small, and the efficiency will rapidly decrease when increasing the text size, also these methods sometimes have a low level of security, this level will depend on the PK length and sometimes it may be hacked. In this paper, a new method will be introduced to improve the data protection level by using a changeable secrete speech file to generate PK. Highly Secure Data Encryption (HSDE) method will be implemented and tested for data quality levels to ensure that the HSDE destroys the data in the encryption phase, and recover the original data in the decryption phase. Some standard methods of data cryptography will be implemented; comparisons will be done to justify the enhancements provided by the proposed method.

Isolation and Analysis of Temperature Sensitive Mutants in Aspergillus nidulans (Aspergillus nidulans 온도감수성 돌연변이주의 분리 및 분석)

  • 박찬규;강현삼
    • Korean Journal of Microbiology
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    • v.16 no.3
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    • pp.111-121
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    • 1978
  • About 40 temperature-sensitive mutants have been isolated as a preliminary step to study the spore germination, the cell cycle, and the control of macromolecular synthesis in Aspergillus nidulans. To obtain temperature-sensitive mutants rapidly and effectively, the selective enrichment method using antifungal antibiotic nystatin was developed. Based on the data which had applied to the concentration of auxotrophic mutants by the earlier investigators, the optimal concentration and the time of treatment at the nonpermissive temeprature were determined as 50 to 100 units per ml and 4.5 hr., respectively. Out of 41 ts mutants assigned to the strain symbol PK, thirteen that seemed to be arrested at the earlystage of spore germination were subjected to the further cytological and genetic analysis. Elght of these mutants are able to form germ tube and five not. Staining with acid fuchsin for the 5PK strains shows that one irreversible mutant, PK6 strain able to form germ tube, accumulate mitotic spindle, being arrested in mitosis. Another PK15 and PK23 strain have more than one intact nucleolus without germ tube formation at the restrictive temperature. the temperature-senstive mutation in PK12 strain, the onlystrain which is able occurred in certain gene specific for the germination of spore. All of the ts markers are recessive and complement each other in heterokaryon between two different ts markers at the restrictive temperature.

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Comparative Study on the Production of Interferons from Porcine Blood Leukocytes (돼지의 백혈구 인터폐론 생산에 관한 비교연구)

  • Han, Su-nam;Lee, Jang-nag;Lee, Chang-eop
    • Korean Journal of Veterinary Research
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    • v.27 no.2
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    • pp.191-200
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    • 1987
  • Attempts were to produce porcine leukocyte interferon(PorLeIF) and porcine immune interferon (PorIIF) in the culture of porcine leukocytes. The interferons produced were tested for antiviral activity against vesicular stomatitis virus on poreine-derived PK(15) cells, human-derived FL cells, and Korean native black goat-derived BGK cells. The results were summarized as follws: 1. In the isolation of porcine leukocytes, the mean isolation rate by the buffy coat separation method (28.7%) was higher than that by the hydroxyethyl starch-RBC sedimentation method (9.2%). 2. When NDV(BI)-induced PorLeIFs were assyed on PK(15) cells and FL cells, the mean titers were 129 IU/ml and 72 IU/ml respectively, being 55.8% of the activity in homologous species system expressed in heterologous system. 3. The activities of PHA P-induced PorIIFs were 197 IU/ml on PK (15) cells and no activity on human FL cells. The mean antiviral activity of PorIIF was 1.5 times that of PorLeIF in PK (15) cells. 4. The cytopathic effect of vesicular stomatitis virus was observed in BGK cells derived from Korean native black goat kidney permitting interferon assay on the cells. While the cross-species antiviral activity of reference human ${\alpha},\;{\beta}-interferon$ was observed on the cells, PorLeIF and PorIIF did not show any activity.

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Cpk Index Estimation under Tw (the weakest t-norm)-based Fuzzy Arithmetic Operations

  • Hong, Dug-Hun
    • International Journal of Fuzzy Logic and Intelligent Systems
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    • v.8 no.3
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    • pp.170-174
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    • 2008
  • The measurement of performance of a process considering both the location and the dispersion of information about the process is referred to as the process capacity indices (PCIs) of interest, $C_{pk}$. This information is presented by the mean and standard deviation of the producing process. Linguistic variables are used to express the evaluation of the quality of a product. Consequently, $C_{pk}$ is defined with fuzzy numbers. Lee [Eur. J. Oper. Res. 129(2001) 683-688] constructed the definition of the $C_{pk}$ index estimation presented by fuzzy numbers and approximated its membership function using the "min" - norm based Zadeh's extension principle of fuzzy sets. However, Lee's result was shown to be invalid by Hong [Eur. J. Oper. Res. 158(2004) 529-532]. It is well known that $T_w$ (the weakest t-norm)-based addition and multiplication preserve the shape of L-R fuzzy numbers. In this paper, we allow that the fuzzy numbers are of L-R type. The object of the present study is to propose a new method to calculate the $C_{pk}$ index under $T_w-based$ fuzzy arithmetic operations.

Preparation of Polyketone Micro/nanofiber Membrane based on Electrospinning Condition and Its Application in Oil-Water Separation (전기방사법의 제조 조건에 따른 폴리케톤 마이크로/나노섬유 분리막 제조 및 유수 분리 적용)

  • Hou, Jian;Yun, Jaehan;Park, Chanju;Choi, Jinwon;Jeon, Sungil;Lee, Chang Hyun;Byun, Hongsik
    • Membrane Journal
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    • v.31 no.6
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    • pp.426-433
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    • 2021
  • In this study, a novel material polyketone (PK) was chosen and PK micro/nano fiber membranes were fabricated via electrospinning method under various conditions. After that, the potential application in oil-water separation was thoroughly investigated. The surface of microfiber membrane formed under high humidity especially became much rougher than that formed under low humidity. When salt was added to the spinning solution, the diameter of fibers was reduced up to 90% and the nanofiber membranes could be formed. The oil/water emulsions were prepared and separated under gravity condition using the manufactured rPK-LNC and PK-H membranes. The separation characteristics was evaluated by measuring total organic carbon (TOC) and turbidity. Meanwhile, the changes in the physical properties of fiber membranes under various conditions and with or without salt, as well as the changes in oil water separation characteristics were also studied.