• Toxicological Research
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• v.29 no.1
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• pp.53-60
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• 2013

Studies on milk transfer of drugs in non-human primates (NHPs) are among the crucial components in the assessment of peri- and postnatal toxicity because of the similarity between NHPs and humans. To evaluate the milk transfer of valproic acid (VPA) in NHPs, the toxicokinetics of VPA, an antiepileptic drug, were studied in pregnant cynomolgus monkeys. VPA was administered once daily to pregnant cynomolgus monkeys at doses of 0, 30, 90, and 270 mg/kg by oral gavage from Day 100 of gestation (GD 100) to Day 31 of lactation (LD 31). Concentrations of VPA and its metabolite, 4-ene-VPA, in the maternal plasma on GD 100, GD 140, and LD 30, and concentrations of VPA and 4-ene-VPA in the offspring plasma and milk on LDs 30 and 31, respectively, were quantified using liquid chromatography tandem mass spectrometry (LC/MS/MS). After administration of a single oral dose of VPA to pregnant monkeys on GD 100, the concentrations of VPA and 4-ene-VPA were generally quantifiable in the plasma of all treatment groups up to 24 hr after administration, which showed that VPA was absorbed and that the monkeys were systemically exposed to VPA and 4-ene-VPA. After administration of multiple doses of VPA to the monkeys, VPA was detected in the pup's plasma and in milk taken on LD 30 and LD 31, respectively, which showed that VPA was transferred via milk, and the pup was exposed to VPA. Further, the concentration of VPA in the milk increased with an increase in the dose. Extremely low concentrations of 4-ene VPA were detected in the milk and in the pup plasma. In conclusion, pregnant monkeys were exposed to VPA and 4-ene-VPA after oral administration of VPA at doses of 30, 90, and 270 mg/kg/day from GD 100 to LD 31. VPA was transferred via milk, and the VPA exposure to the pup increased with an increase in the dose of VPA. The metabolite, 4-ene VPA, was present in extremely low concentrations (< 0.5 ${\mu}g/ml$) in the milk and in the pup plasma. In this study, we established methods to confirm milk transfer in NHPs, such as mating and diagnosis of pregnancy by examining gestational sac with ultrasonography, collection of milk and pup plasma and determination of toxicokinetics, using cynomolgus monkeys.

• Archives of Pharmacal Research
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• v.29 no.6
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• pp.514-519
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• 2006

A simple HPLC method using UV detection was developed and validated for the determination of levodropropizine (LDP) In dog plasma. The sample was prepared for injection using a liquid-liquid extraction method with 1-phenypiperazine as the internal standard. The mobile phase was methanol - diethylamine solution (0.05 M) (20:80, v/v, pH adjusted to 3.0 with $H_3PO_4$) with a detection wavelength of 240 nm. The limit of quantitation (LOQ) of LDP in a biological matrix was determined to be 25.25 ng/mL. The calibration curve was linear across the concentration range of 25.25 to 2020 ng/mL. The intra-day and inter-day precision values (CV%) were within 7% and accuracy (R.E. %) was within 6% of the nominal values for medium (252.5 ng/mL) and high (2020 ng/mL) LDP concentrations. For the LDP concentration at the LOQ, the intra-day and inter-day precision and accuracy were within 20% and 10%, respectively. The average absolute recovery for LDP was 70.28%. This method was successfully used to analyze plasma samples in a steady-state bioavailability study of a newly developed sustained-release LDP tablets (SR) using immediate-release tablets (IR) as the reference. The relative bioavailability of the SR was determined to be $106.3\;{\pm}\;12.8%$ (n=6). The $C_{max}$ of the SR was significantly lower (p<0.05), and the $t_{max}$ was significantly longer than that of the IR (p<0.05). The results of ANOVA and two one-sided tests indicated that the SR exhibited acceptable sustained release properties and was bioequivalent to the IR.

• Mass Spectrometry Letters
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• v.8 no.2
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• pp.23-28
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• 2017

Arctigenin is the main active ingredient of Fructus Arctii, which has been reported with a variety of therapeutic activities including anti-cancer, anti-inflammation, anti-virus, and anti-obesity effects. In this study, a simple and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of arctigenin in rat plasma. The assay utilized a simple protein precipitation with methanol and the mobile phase consisted of 100% methanol and water containing 0.1% formic acid (65:35 v/v). Arctigenin and the internal standard (psoralen) were monitored using a positive electrospray turbo ionspray mode with multiple reaction monitoring transitions of m/z $373.2{\rightarrow}136.9$ and m/z $187.2{\rightarrow}130.9$, respectively, and total chromatographic run time was within 5 min. The lower limit of quantification (LLOQ) of arctigenin was 5 ng/mL in the rat plasma. The intra- and inter-day accuracy of arctigenin at LLOQ and matrix-matched quality control samples ranged 97.4 - 104.8% and 97.2 - 102.0%, respectively. The intra-day precision was within 4.80% and the inter-day precision was within 5.92%. Application of the present method was demonstrated through a pharmacokinetic study after intravenous and oral administration of arctigenin in male Sprague Dawley rats.

• Journal of Nutrition and Health
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• v.53 no.6
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• pp.663-675
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• 2020

Purpose: The aim of this study was to measure the sodium content of the solid and liquid components of soup-based dishes (SBD) including Korean soup, stew, noodle/dumplings, and watery kimchi and to compare the sodium content in the dishes from home, schools, and restaurants in Seoul. Methods: The dishes were divided into 3 groups, namely home, restaurant and school food. We separated the dishes into solid and liquid to measure the weight, salinity, and sodium content. The sodium content of the dishes was analyzed using inductively coupled plasma atomic emission spectrometry. Results: The proportion of sodium content in the liquid component of SBD were 65.2%-66.7% in soup, 49.8%-61.2% in stew, 48.7%-56.7% in noodle/dumpling, and 43.7%-73.2% in watery kimchi. The sodium content per 100 g of the whole dishes of the same kind from the schools was significantly lower than that from the restaurants and home. However, there was no significant difference in sodium content per 100 g of whole dishes between the restaurants and home. The sodium content per 100 g of liquid in the same kind of dishes from the schools was significantly lower than those from the restaurants and home, and that from home was significantly lower than from the restaurants. Conclusion: The sodium content of the liquid in SBD accounted for at least about half of the total sodium content of the whole dishes. It is important to establish a separate database with the sodium content in the solid and liquid portions of SBD and to evaluate how much liquid and/or solid would be consumed to estimate individual sodium intake more accurately. Also, it should be noted that the sodium content varies with the origin of the dishes, whether dishes were from home, restaurants, or schools.

• Nuclear Engineering and Technology
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• v.37 no.5
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• pp.401-422
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• 2005

We review here research and development progress achieved in US Plasma Chamber technology roughly over the last decade. In particular, we focus on two major programs carried out in the US: the APEX project (1998-2003) and the US ITER TBM activities (2003-present). The APEX project grew out of the US fusion program emphasis in the late 1990s on more fundamental science and innovation. APEX was commissioned to investigate novel technology concepts for achieving high power density and high temperature reactor coolants. In particular, the idea of liquid walls and the related research is described here, with some detailed examples of liquid metal and molten salt magnetohydrodynamic and free surface effects on flow control and heat transfer. The ongoing US ITER Test Blanket Module (TBM) program is also described, where the current first wall/blanket concepts being considered are the dual coolant lead lithium concept and the solid breeder helium cooled concepts, both using ferritic steel structures. The research described for these concepts includes both thermofluid MHD issues for the liquid metal coolant in the DCLL, and thermomechanical issues for ceramic breeder packed pebble beds in the solid breeder concept. Finally, future directions for ongoing research in these areas are described.

• Biomolecules & Therapeutics
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• v.6 no.2
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• pp.213-218
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• 1998

A novel in situ-gelling and mucoadhesive acetaminophen liquid suppository was developed to improve the patient compliance of conventional solid suppository. In this study, acetaminophen liquid suppository, Likipe $n_{R}$, ［aminophen/Poloxamer 407/Poloxamer 188/so4ium alginate (5/15/19/0.6%)] with relation temperature at 30-36 "C and suitable gel strength and bioadhesive force, dissolution pattern similar to conventional solid type suppository, Suspe $n_{R}$, was developed. Furthermore, the bioequivalence of two acetaminophen products was evaluated in 16 normal male volunteers (age 22-27 yr, body weight 56-72 kg) following sidle rectal administration. Test product was Likipe $n_{R}$ suppository (Dong-Wha Pharm. Corp., Korea)and reference product was Suspe $n_{R}$204-212 suppository (Hanmi Pharm. Corp., Korea). Both products contain 125 mg of acetaminophen. Four Suppositories of the test and the reference product were administered to the volunteers, respectively, by randomized two period cross-over study (2$\times$2 Latin square method). The determination of acetaminophen was accomplished using HPLC. 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_{-2}$4h/) (30.14$\pm$8.64 vs 27.98$\pm$ 6.53 $\mu$g .h/ml), maximum plasma concentration ( $C_{max}$) (3.29$\pm$0.87 vs 3.60$\pm$0.66 $\mu$g/ml) and time to maximum plasma concentration ( $T_{max}$) (2.91 $\pm$0.55 vs 2.69$\pm$0.60 h). The differences of mean AUCo $_{24h}$, C-a. and T-between the two products (7.18%, 9.58% and 7.53%, respectively) were less than 20%. The power (1-7) and treatment difference ($\Delta$) for AU $Co_{24h}$, $C_{max}$ and $T_{max}$ were more than 0.8 and less than 0.2, respectively at $\alpha$=0.1. The confidence limits for AU $Co_{24h}$, $C_{max}$ and $T_{max}$ (-0.81 ~13.55%, -1.56~ 17.60 and -3.81 ~18.87%, respectively) were less than $\pm$ 20% at $\alpha$=0.1. These results suggest that the bioavailability of Likipe $n_{R}$ suppository is not significantly different from that of Suspe $n_{R}$ suppsitory. Therefore, two products are bio-equivalent based on the current results.results.lts.sults.results.lts.

• Animal Bioscience
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• v.35 no.2
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• pp.224-235
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• 2022

Objective: Cage rearing has critical implications for the laying duck industry because it is convenient for feeding and management. However, caging stress is a type of chronic stress that induces maladaptation. Environmental stress responses have been extensively studied, but no detailed information is available about the comprehensive changes in plasma metabolites at different stages of caging stress in ducks. We designed this experiment to analyze the effects of caging stress on performance parameters and oxidative stress indexes in ducks. Methods: Liquid chromatography tandem mass spectrometry (LC/MS-MS) was used to determine the changes in metabolites in duck plasma at 5 (CR5), 10 (CR10), and 15 (CR15) days after cage rearing and traditional breeding (TB). The associated pathways of differentially altered metabolites were analyzed using Kyoto encyclopedia of genes and genomes (KEGG) database. Results: The results of this study indicate that caging stress decreased performance parameters, and the plasma total superoxide dismutase levels were increased in the CR10 group compared with the other groups. In addition, 1,431 metabolites were detected. Compared with the TB group, 134, 381, and 190 differentially produced metabolites were identified in the CR5, CR10, and CR15 groups, respectively. The results of principal component analysis (PCA) show that the selected components sufficiently distinguish the TB group and CR10 group. KEGG analysis results revealed that the differentially altered metabolites in duck plasma from the CR5 and TB groups were mainly associated with ovarian steroidogenesis, biosynthesis of unsaturated fatty acids, and phenylalanine metabolism. Conclusion: In this study, the production performance, blood indexes, number of metabolites and PCA were compared to determine effect of the caging stress stage on ducks. We inferred from the experimental results that caging-stressed ducks were in the sensitive phase in the first 5 days after caging, caging for approximately 10 days was an important transition phase, and then the duck continually adapted.

• Korean Journal of Biological Psychiatry
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• v.4 no.1
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• pp.84-94
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• 1997

This study was done to examine changes of plasma homovanillic acid(HVA), 5-hydroxyindoleacetic acid(5-HIAA), and HVA/5-HIAA ratio during an 8-week clozapine trial and to investigate the relationship between the plasma monoamine metabolites and treatment responses. Twenty-seven chronic schizophrenic patiens were treated for 8 weeks with clozapine. The psychopathology was assessed at baseline just clozapine trial and then every 2 weeks until the end of 8-week clozapine treatment using the Positive and Negative Syndrome Scale(PANSS) and the Clinical Global Impression scale(CGI). The plasma HVA and 5-HIAA levels were measured also biweekly using high preformance liquid chromatography with electrochemical detection method. Plasma HVA and 5-HIAA levels were significantly decreased during a 8-week clozapine treatment, although plasma HVA/5-HIAA ratio showed no significant change. The changes of plasma HVA levels were in significant correlations with the changes of PANSS positive scores, of general psychophathology scores, and changes of total socres. The changes of plasma 5-HIAA levels were in signfificant correlations with the changes of PANSS negative scores. But the changes of plasma HVA/5-HIAA ratio had no significant correlation with any PANSS subscale score changes. 48% of the patients treated with clozapine was categorized as responders, who showed at least a 20% decrease in PANSS total socre and a CGI severity score of mildly ill or less(${\leq}3$) at the end pint of the study. The baseline plasma HVA levels and HVA/5-HIAA ratio were significantly higher in responders(N=13) than in nonresponders (N=14). But no significant difference in baseline levels of plasma 5-HIAA was found between responders and nonresponders. At the end point of the study, there was significant difference in the change of plasma HVA between responders(40.3% decrement) and nonresponders(3.1% increment). But no signficant differences in the change of plasma 5-HIAA and the change of plasma HVA/5-HIAA ratio between responders and nonresponders were observed. These results suggest that the antipsychotic effect of clozapine on positive symptoms may be associated with dopaminergic blocking activity, and that on negative symptoms may be associated with serotonergic blocking activity. The baseline plasma HVA levels and the change of HVA levels from baseline may be useful predictors of treatment response with clozapine.

• Journal of the Korean Institute of Illuminating and Electrical Installation Engineers
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• v.24 no.2
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• pp.106-112
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• 2010

In order to compete with other flat display devices such as Liquid Crystal Displays (LCDs) and organic light emitting diodes (OLEDs), Plasma Display Panels (PDPs) require to have high performances like high image quality, low power consumption and high speed driving. In this paper, Fe doped MgO protective layer was introduced for higher performance. Both the surface characteristics of the deposited thin films and the electro-optical properties of 4 inch test panels were investigated. It has been demonstrated experimentally that ac PDP with Fe doped MgO protective layer has lower discharge voltage than that of undoped MgO film, which corresponds to measured secondary electron emission coefficients. The crystallinity and surface roughness of thin films were determined by XRD patterns and AFM images. In addition, ac PDP with Fe doped MgO protective layer has improved address discharge time lag for high speed driving.

• 한국정보디스플레이학회:학술대회논문집
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• 2008.10a
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• pp.107-108
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• 2008

The spectacular development of AMLCDs, been made possible by a-Si:H technology, still faces two major drawbacks due to the intrinsic structure of a-Si:H, namely a low mobility and most important a shift of the transfer characteristics of the TFTs when submitted to bias stress. This has lead to strong research in the crystallization of a-Si:H films by laser and furnace annealing to produce polycrystalline silicon TFTs. While these devices show improved mobility and stability, they suffer from uniformity over large areas and increased cost. In the last decade we have focused on microcrystalline silicon (${\mu}c$-Si:H) for bottom gate TFTs, which can hopefully meet all the requirements for mass production of large area AMOLED displays [1,2]. In this presentation we will focus on the transfer of a deposition process based on the use of $SiF_4$-Ar-$H_2$ mixtures from a small area research laboratory reactor into an industrial gen 1 AKT reactor. We will first discuss on the optimization of the process conditions leading to fully crystallized films without any amorphous incubation layer, suitable for bottom gate TFTS, as well as on the use of plasma diagnostics to increase the deposition rate up to 0.5 nm/s [3]. The use of silicon nanocrystals appears as an elegant way to circumvent the opposite requirements of a high deposition rate and a fully crystallized interface [4]. The optimized process conditions are transferred to large area substrates in an industrial environment, on which some process adjustment was required to reproduce the material properties achieved in the laboratory scale reactor. For optimized process conditions, the homogeneity of the optical and electronic properties of the ${\mu}c$-Si:H films deposited on $300{\times}400\;mm$ substrates was checked by a set of complementary techniques. Spectroscopic ellipsometry, Raman spectroscopy, dark conductivity, time resolved microwave conductivity and hydrogen evolution measurements allowed demonstrating an excellent homogeneity in the structure and transport properties of the films. On the basis of these results, optimized process conditions were applied to TFTs, for which both bottom gate and top gate structures were studied aiming to achieve characteristics suitable for driving AMOLED displays. Results on the homogeneity of the TFT characteristics over the large area substrates and stability will be presented, as well as their application as a backplane for an AMOLED display.