• Proceedings of the KSAR Conference
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• 2003.06a
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• pp.45-45
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• 2003

Human papillomavirus type 16(HPV16) has been known to the major factor for the development of uterine cervical carcinomas. We have extended these studies to investigate the in vivo activities of HPV-16 E6/E7 when expressed in squamous epithelia of transgenic mice. Grossly, hK14HPV16E6/E7 transgenic mice had multiple phenotypes, including wrinkled skin that was apparent prior to the appearance of hair on neonates, thickened ears, and loss of hair in adults. In the transgenic mice, the wrinkled skin phenotype on the body and legs died at the age of 3∼4 weeks. Histological analysis of demonstrated that E6/E7 causes epidermal hyperplasia in multiple transgenic lineages with high penetrance. This epithelial hyperplasia was characterized by an expansion of the proliferating compartment and an expansion of the keratinocyte and was associated with hyperkeratosis. These transgenic mice expressed E6/E7 transgene mainly in skin, heart, pancreas and kidney. Hyperplasia was found at the skin. The enzyme activities of GR, GPx and CuZnSOD were measured from the transgene cause keratinocyte at the skin. The specific enzyme activities were significantly higher in transgenic mice skin compared to the normal mice skin. Thus these transgenic mice may be useful for the develpment of antioxidant enzymes or other therapies for HPV-associated hyperkeratosis.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.4
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• pp.317-325
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• 2007

Purpose: Biological parameters can be quantified using dynamic PET data with compartment modeling and Nonlinear Least Square (NLS) estimation. However, the generation of parametric images using the NLS is not appropriate because of the initial value problem and excessive computation time. In irreversible model, Patlak graphical analysis (PGA) has been commonly used as an alternative to the NLS method. In PGA, however, the start time ($t^*$, time where linear phase starts) has to be determined. In this study, we suggest a new Multiple Linear Analysis for irreversible radiotracer (MLAIR) to estimate fluoride bone influx rate (Ki). Methods: $[^{18}F]Fluoride$ dynamic PET scans was acquired for 60 min in three normal mini-pigs. The plasma input curve was derived using blood sampling from the femoral artery. Tissue time-activity curves were measured by drawing region of interests (ROls) on the femur head, vertebra, and muscle. Parametric images of Ki were generated using MLAIR and PGA methods. Result: In ROI analysis, estimated Ki values using MLAIR and PGA method was slightly higher than those of NLS, but the results of MLAIR and PGA were equivalent. Patlak slopes (Ki) were changed with different $t^*$ in low uptake region. Compared with PGA, the quality of parametric image was considerably improved using new method. Conclusion: The results showed that the MLAIR was efficient and robust method for the generation of Ki parametric image from $[^{18}F]Fluoride$ PET. It will be also a good alternative to PGA for the radiotracers with irreversible three compartment model.

• Korean Journal of Veterinary Research
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• v.35 no.4
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• pp.815-822
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• 1995

The toxicokinetics of rifapentine was studied after an oral administration to beagle dogs. High-performance liquid chromatography(HPLC) using column-switching technique was performed to determine the serum concentrations of rifapentine. The pharmacokinetic profiles of rifapentine were analysed using one-compartment open model. Following a single oral administration of 10mg/kg, pharmacokinetic parameters were determined as follows: maximum serum concentration($C_{max}$), $28.90{\mu}g/ml$; maximum concentration time($T_{max}$), 3.7hr; elimination half-life($t_{1/2}$, 4.7hr; area under the curve(AUC), $339.0{\mu}g{\cdot}hr/ml$; volume of disiribution/bioavailability (Vd/F), 0.21 l/kg; lag time, 24min; absorption rate constant($k_a$), $0.445hr^{-1}$; elimination rate constant($k_{el}$), $0.148hr^{-1}$. After 6 month multiple oral doses of 10mg/kg/day, parameters were as follows: $C_{max}$, $34.40{\mu}g/ml$; $T_{max}$, 2.6hr; $t_{1/2}$, 6.7hr; AUC, $391.3{\mu}g{\cdot}hr/ml$; Vd/F, 0.291/kg; $k_a$, $0.976hr^{-1}$; $k_{el}$, $0.104hr^{-1}$. The consistant kinetic parameters after a single and multiple oral administration show that there was no accumulation of rifapentine after 6 month oral administration. We also simulated the concentration of rifapentine after oral multiple administration of 10 and 50mg/kg/ day, based on the parameters obtained form the single administration. The measured serum concentrations of rifapentine were well fitted to the simulated results. The simulated results show that rifapentine readily reaches to steady-state after about 3 doses and the steady-state serum concentrations($C_{ss}$) are fluctuated in between $2.2{\sim}25.2{\mu}g/ml$, and $10.6{\sim}125.2{\mu}g/ml$ at the doses of 10 and 50mg/kg/day, respectively.

• Journal of Fisheries and Marine Sciences Education
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• v.26 no.2
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• pp.316-321
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• 2014

The pharmacokinetics of erythromycin (EM) after oral administration was studied in the cultured olive flounder, Paralichthys olivaceus, using LC/MS/MS. After single- or multiple-dose administration of EM (50, 100, 200 mg/kg body weight and 50 mg/kg for 5 days) by oral route in olive flounder ($350{\pm}40g$, $22{\pm}0.5^{\circ}C$), the concentration in the serum was determined at 1, 3, 6, 9, 24, 72, 120, 168, 264, 360, 504 and 720 h post-dose. The kinetic profile of absorption, distribution and elimination of EM in serum were analyzed fitting to a two-compartment model by WinNonlin program. The area under the concentration-time curve (AUC), maximum concentration ($C_{max}$), time for maximum concentration ($T_{max}$) following oral administration of 50, 100 and 200 mg/kg b.w. and 50 mg for 5 days. EM was $165.3hr^*{\mu}g/m{\ell}$ ($C_{max}$, $34.63{\mu}g/m{\ell}$; $T_{max}$, 1.56 hr), $212.8hr^*{\mu}g/m{\ell}$ ($C_{max}$, $60.38{\mu}g/m{\ell}$; $T_{max}$, 3.99 hr), and $592.37hr^*{\mu}g/m{\ell}$ ($C_{max}$, $63.01{\mu}g/m{\ell}$; $T_{max}$, 4 hr), respectively. The results of this study related to dosage and ${\mu}{\cdot}$withdrawal times could be used for prescription of EM in field for the treatment of bacterial diseases in olive flounder.

• Korean Journal of Clinical Pharmacy
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• v.27 no.4
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• pp.258-266
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• 2017

Objective: To develop a population pharmacokinetics (PK)/pharmacodynamics (PD) model for alcohol in healthy volunteers and to elucidate individual characteristics to affects alcohol's PK or PD including dissolved oxygen. Methods: Following multiple intakes of total 540 mL alcohol (19.42 v/v%) to healthy volunteer, blood alcohol concentration was measured using a Breathe alcohol analyser (Lion SD-400 $Alcolmeter^{(R)}$). A sequential population PK/PD modeling was performed using NONMEM (ver 7.3). Results: Eighteen healthy volunteer were included in the study. PK model of alcohol was well explained by one-compartment model with first-order absorption and Michaelis-Menten elimination kinetics. $K_a$, V/F, $V_{max}$, $K_m$ is $8.1hr^{-1}$, 73.7 L, 9.65 g/hr, 0.041 g/L, respectively. Covariate analysis revealed that gender significantly influenced $V_{max}$ (Male vs Female, 9.65 g/hr vs 7.38 g/hr). PD model of temporary systolic blood pressure decreasing effect of alcohol was explained by biophase model with inhibitory $E_{max}$ model. $K_{e0}$, $I_{max}$, $E_0$, $IC_{50}$ were $0.23hr^{-1}$, 44.9 mmHg, 138 mmHg, 0.693 g/L, respectively. Conclusion: Model evaluation results suggested that this PK/PD model was robust and has good precision.

• Journal of Korean Foot and Ankle Society
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• v.15 no.2
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• pp.86-91
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• 2011

Purpose: To evaluate the effectiveness as well as correct the post-traumatic severe ankle equinus deformity by conducting the treatment surgery, which is divided into 2 stages, soft tissue adhesiolysis and ankle arthrodesis. Materials and Methods: We have conducted the methods, which are Z-plasty Achilles tendon lengthening, multiple capsulotomy and tendon lengthening (flexor hallucis longus muscle, flexor digitorum longus, posterior tibialis tendon) for 10 patients who has shown equinus deformity after post-traumatic compartment syndrome due to the injury. The average age of patients was 33.7 year-old; there were 8 men and 2 women, and the follow up period was 13 months (6~31 mon). Outcomes were rated based on American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score, Visual Analogue Scale (VAS) and patient's satisfaction after operation. Results: The average degree of preoperative equinus deformity was 64 degree (-60~-70), and we've obtained AOFAS anklehindfoot score that was evaluated after 4 months of 2nd operation which was 76.7 score on average. We've also checked the decreased pain score from all of the patients according to the fact that the average VAS before the surgery was 6 (4~8), but it reduced to 3 (1~4). The patient's satisfaction showed generally great satisfactions which was 5 cases were excellent, 2 cases were good, and 3 cases were fair. Conclusion: The two staged surgical treatment of post -traumatic severe ankle equinus deformity, which was conducted of soft tissue adhesiolysis and arthrodesis, could be one of the effective methods to improve patients walking ability.

• Molecules and Cells
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• v.22 no.2
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• pp.210-219
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• 2006

Dynamin-related protein 2A (AtDRP2A, formally ADL6), a member of the dynamin family, is critical for protein trafficking from the TGN to the central vacuole. However, the mechanism controlling its activity is not well understood in plant cells. We isolated Arabidopsis sec13 homolog1 (AtSeh1) that interacts with AtDRP2A by a yeast two-hybrid screening. AtSeh1 has four WD40 motifs and amino acid sequence homology to Sec13, a component of COPII vesicles. Coimmunoprecipitation and protein pull-down experiments demonstrated specific interaction between AtSeh1 and AtDRP2A. AtSeh1 bound to the pleckstrin homology domain of AtDRP2A in competition with the C-terminal domain of the latter, and this resulted in inhibition of the interaction between AtDRP2A and PtdIns3P in vitro. AtSeh1 localized to multiple locations: the nucleus, the prevacuolar compartment and the Golgi complex. Based on these results we propose that AtSeh1 plays a role in regulating cycling of AtDRP2A between membrane-bound and soluble forms.

• Translational and Clinical Pharmacology
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• v.26 no.4
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• pp.166-171
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• 2018

Although there are many commercially available training software programs for pharmacokinetics, they lack flexibility and convenience. In this study, we develop simulation software to facilitate pharmacokinetics education. General formulas for time courses of drug concentrations after single and multiple dosing were used to build source code that allows users to simulate situations tailored to their learning objectives. A mathematical relationship for a 1-compartment model was implemented in the form of differential equations. The concept of population pharmacokinetics was also taken into consideration for further applications. The source code was written using R. For the convenience of users, two types of software were developed: a web-based simulator and a standalone-type application. The application was built in the JAVA language. We used the JAVA/R Interface library and the 'eval()' method from JAVA for the R/JAVA interface. The final product has an input window that includes fields for parameter values, dosing regimen, and population pharmacokinetics options. When a simulation is performed, the resulting drug concentration time course is shown in the output window. The simulation results are obtained within 1 minute even if the population pharmacokinetics option is selected and many parameters are considered, and the user can therefore quickly learn a variety of situations. Such software is an excellent candidate for development as an open tool intended for wide use in Korea. Pharmacokinetics experts will be able to use this tool to teach various audiences, including undergraduates.

• Journal of Veterinary Science
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• v.25 no.4
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• pp.58.1-58.8
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• 2024

Importance: Over the past decade, catfish farming has increased in Southeast Asia. However, there has been no existing for pharmacokinetic data in the hybrid catfish (Clarias macrocephalus x C. gariepinus). Objective: This study was designed to evaluate the pharmacokinetic characteristics of oxytetracycline (OTC) in the hybrid catfish, following single intravascular (IV) or oral (PO) administration at a single dosage of 50 mg/kg body weight (BW). Methods: In total, 140 catfish (each about 100-120 g BW) were divided into two groups (n = 70). Blood samples (0.6-0.8 mL) were collected from ventral caudal vein at pre-assigned times up to 144 h (sparse samples design). OTC plasma concentrations were analyzed using high-performance liquid chromatography-photodiode array detector. Results: The pharmacokinetic parameter of OTC was evaluated using a non-compartment model. OTC plasma concentrations were detectable for up to 144 and 120 h after IV and PO, respectively. The elimination half-life value of OTC was long with slow clearance after IV administration in hybrid catfish. The average maximum concentration value of OTC was 2.72 ㎍/mL with a time at the maximum concentration of 8 h. The absolute PO bioavailability was low (2.47%). Conclusions and Relevance: These results showed that PO administration of OTC at a dosage of 50 mg/kg BW was unlikely to be effective for clinical use in catfish. The pharmacodynamic properties and clinical efficacy of OTC after multiple medicated feed are warranted.

• Proceedings of the Korean Society of Developmental Biology Conference
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• 2003.10a
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• pp.106-106
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• 2003

Human papillomavirus type 16(HPV16) has been known to the major factor for the development of uterine cervical carcinomas. We have extended these studies to investigate the in vivo activities of HPV-16 E6/E7 when expressed in squamous epithelia of transgenic mice. Grossly, hK14HPV16E6/E7 transgenic mice had multiple phenotypes, including wrinkled skin that was apparent prior to the appearance of hair on neonates, thickened ears, and loss of hair in adults. In the transgenic mice, the wrinkled skin phenotype on the body and legs died at the age of 3-4 weeks. Histological analysis of demonstrated that E6/E7 causes epidermal hyperplasia in multiple transgenic lineages with high penetrance. This epithelial hyperplasia was characterized by an expansion of the proliferating compartment and an expansion of the keratinocyte and was associated with hyperkeratosis. These transgenic mice expressed E6/E7 transgene mainly in skin, heart, pancreas and kidney. Hyperplasia was found at the skin. The enzyme activities of GR, GPx and CuZnSOD were measured from the transgene cause keratinocyte at the skin. The specific enzyme activities were significantly higher in transgenic mice skin compared to the normal mice skin. Thus these transgenic mice may be useful for the develpment of antioxidant enzymes or other therapies for HPV-associated hyperkeratosis.