Pharmacokinetics and pharmacodynamics of LC15-0444, a novel dipeptidyl peptidase IV inhibitor, after multiple dosing in healthy volunteers

Lim, Kyoung Soo,Cho, Joo-Youn,Kim, Bo-Hyung,Kim, Jung-Ryul,Kim, Hwa-Sook,Kim, Dong-Kyu,Kim, Sung-Ho,Yim, Hyeon Joo,Lee, Sung-Hack,Shin, Sang-Goo,Jang, In-Jin,Yu, Kyung-Sang Blackwell Publishing Ltd 2009 British journal of clinical pharmacology Vol.68 No.6

<P><B>WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT</B></P><P>• The importance of efficient drug development using biomarkers has been increasingly emphasized, from preclinical studies to clinical trials.</P><P>• However, as yet few ‘validated’ or ‘qualified’ biomarkers are used in early-stage drug development in terms of clinical pharmacology and disease pathophysiology.</P><P><B>WHAT THIS STUDY ADDS</B></P><P>• This first-time-in-human study provides evidence of the pharmacological activity of LC15-0444 in humans, by using dipeptidyl peptidase IV activity and active glucagon-like peptide-1 concentrations.</P><P>• LC15-0444 possesses pharmacokinetic and pharmacodynamic characteristics that support a once-daily dosing regimen.</P><P>AIMS</P><P>LC15-0444 is a selective and competitive inhibitor of dipeptidyl peptidase (DPP) IV with potential for the treatment of Type 2 diabetes. The aim was to investigate the pharmacokinetic (PK) and pharmacodynamic (PD) profiles after multiple oral ascending doses of LC15-0444 in healthy male subjects.</P><P>METHODS</P><P>A dose block-randomized, double-blind, placebo-controlled, parallel group study was performed in three groups with 10 subjects (eight for active drug; two for placebo) per group; each group received 200, 400 or 600 mg of LC15-0444 once daily for 10 days. Blood and urine samples were collected up to 24 h after the first dosing and up to 72 h after the last dosing.</P><P>RESULTS</P><P>The LC15-0444 concentration–time profiles exhibited characteristics of multicompartment disposition. No dose- or time-dependent change in PK parameters was observed. Mean elimination half-life was in a range 16.6–20.1 h in the dose groups. Mean renal clearance and fraction of unchanged drug excreted in urine was 18.6–21.9 and 0.40–0.48 l h<SUP>−1</SUP>, respectively. In the steady state, mean accumulation ratios by dose groups were between 1.22 and 1.31. More than 80% inhibition of DPP IV activity from baseline was sustained for >24 h in all dose groups.</P><P>CONCLUSIONS</P><P>This study provides evidence of the pharmacological activity of LC15-0444 in humans. LC15-0444 possesses PK and PD characteristics that support a once-daily dosing regimen.</P>

Amorphous Li-Zr-O layer coating on the surface of high-Ni cathode materials for lithium ion batteries

Lim, Young Jin,Lee, Sun-Me,Lim, Hayoung,Moon, Bora,Han, Kyu-Sung,Kim, Jin-Ho,Song, Jun-Ho,Yu, Ji-Sang,Cho, Woosuk,Park, Min-Sik Elsevier 2018 ELECTROCHIMICA ACTA Vol.282 No.-

<P><B>Abstract</B></P> <P>Improving cycle performance and rate-capability of lithium ion batteries is necessary in moving toward their use in electric vehicles. Working towards this goal, we propose an amorphous Li-Zr-O coating on the surface of a high-Ni layered transition metal oxide (LiNi<SUB>0.8</SUB>Co<SUB>0.1</SUB>Mn<SUB>0.1</SUB>O<SUB>2</SUB>) <I>via</I> a simple wet process. By using residual Li on the surface of as-prepared LiNi<SUB>0.8</SUB>Co<SUB>0.1</SUB>Mn<SUB>0.1</SUB>O<SUB>2</SUB> particles as a Li source, a non-stoichiometric Li-Zr-O compound can be successfully formed on the surface of LiNi<SUB>0.8</SUB>Co<SUB>0.1</SUB>Mn<SUB>0.1</SUB>O<SUB>2</SUB> particles at a low temperature of 400 °C. The formation of an amorphous Li-Zr-O layer is beneficial in minimizing undesirable side reactions associated with residual Li at the surface and, by extension, improving the cycle performance and rate-capability of LiNi<SUB>0.8</SUB>Co<SUB>0.1</SUB>Mn<SUB>0.1</SUB>O<SUB>2</SUB>. The amorphous Li-Zr-O coated LiNi<SUB>0.8</SUB>Co<SUB>0.1</SUB>Mn<SUB>0.1</SUB>O<SUB>2</SUB> exhibits a high reversible capacity of more than 190 mAh g<SUP>−1</SUP> with improved cycle performance. This simple approach offers easy control of the surface characteristics of LiNi<SUB>0.8</SUB>Co<SUB>0.1</SUB>Mn<SUB>0.1</SUB>O<SUB>2</SUB>, improving the surface stability and enhancing the thermal stability.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A non-stoichiometric Li-Zr-O compound is introduced on the surface of NCM811 particles <I>via</I> a wet-process at a temperature of 400 °C. </LI> <LI> An amorphous Li-Zr-O layer is beneficial in minimizing undesirable side reactions associated with residual Li. </LI> <LI> The amorphous Li-Zr-O coated NCM811 exhibits a high reversible capacity of 190 mAh g<SUP>−1</SUP> and stable cycle performance. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>Amorphous Li-Zr-O coating layers can be uniformly formed on the surface of the particles, which is advantageous in providing suitable Li<SUP>+</SUP> pathways and improving structural stability. In this work, the residual Li on the surface of as-prepared LiNi<SUB>0.8</SUB>Co<SUB>0.1</SUB>Mn<SUB>0.1</SUB>O<SUB>2</SUB> particles can be partially utilized as a Li source for the formation of an amorphous Li-Zr-O coating layer during the coating process.</P> <P>[DISPLAY OMISSION]</P>

Effect of a Non-polymer Titanium Dioxide Thin Film-Coated Stent with Heparin in a Porcine Coronary Restenosis Model

Lim, Kyung Seob,Jeong, Myung Ho,Bae, In Ho,Park, Jun-Kyu,Park, Dae Sung,Shim, Jae Won,Kim, Han Byual,Jin, Mi Rim,Kim, Hyun Kuk,Kim, Sung Soo,Kim, Min Chul,Sim, Doo Sun,Hong, Young Joon,Kim, Ju Han,Ahn The Korean Society on Thrombosis and Hemostasis 2017 Clinical & experimental thrombosis and hemostasis Vol.3 No.2

Design and Implementation of Open-Loop Clock Recovery Circuit for 39.8 Gb/s and 42.8 Gb/s Dual-Mode Operation

Sang-Kyu Lim,Hyunwoo Cho,Jongyoon Shin,고제수 한국전자통신연구원 2008 ETRI Journal Vol.30 No.2

This paper proposes an open-loop clock recovery circuit (CRC) using two high-Q dielectric resonator (DR) filters for 39.8 Gb/s and 42.8 Gb/s dual-mode operation. The DR filters are fabricated to obtain high Q-values of approximately 950 at the 40 GHz band and to suppress spurious resonant modes up to 45 GHz. The CRC is implemented in a compact module by integrating the DR filters with other circuits in the CRC. The peak-to-peak and RMS jitter values of the clock signals recovered from 39.8 Gb/s and 42.8 Gb/s pseudo-random binary sequence (PRBS) data with a word length of 231–1 are less than 2.0 ps and 0.3 ps, respectively. The peak-to-peak amplitudes of the recovered clocks are quite stable and within the range of 2.5 V to 2.7 V, even when the input data signals vary from 150 mV to 500 mV. Error-free operation of the 40 Gb/s-class optical receiver with the dual-mode CRC is confirmed at both 39.8 Gb/s and 42.8 Gb/s data rates.

2015 Nationwide Survey Revealed Barley stripe mosaic virus in Korean Barley Fields

Lim, Hyo-Jin,Seo, Eun-Young,Kim, Hyun-Seung,Kim, Jung-Kyu,Park, Chan-Hwan,Gong, Jun-Su,Kim, Ik-hyun,Han, Sang-huk,Kilcrease, James P.,Furuya, Naruto FACULTY OF AGRIC PUBLICATIONS-KYUSHU UNIV 2016 Journal of the Faculty of Agriculture, Kyushu Univ Vol.61 No.1

<P>A seed transmitted virus has consistently caused significant economic damage to barley crops in Korea in recent years, and may be increasing because many farmers save seed for replanting. Because some barley seed is imported, there is the potential for introduction of new seed transmitted viruses, causing diseases which may spread. Barley cultivation in South Korea is expanding nationwide due to the increasing popularity of health foods, so both production and quality of barley grain is important. Although Barley stripe mosaic virus (BSMV) has been reported previously as a small percentage of all barley viruses present in Korea, increases in imports of barley seed may lead to increased occurrence of this seed transmitted virus. We therefore investigated the virus status of barley crops around Iksan and Wanju. On several newly cultivated barley farms, we observed areas showing symptoms typical of BSMV, and confirmed BSMV infection in 24% of the samples examined. In order to understand the occurrence and seed transmission of Korean BSMV isolates, we examined sequence variation within the Triple Gene Block proteins, and subcellular localization of two of these proteins. The newly identified Korean BSMV isolates show low sequence variability and high sequence homology to previously reported US isolates. With these results, we expect to confirm distribution of barley viruses and possible emerging viruses, which will serve as base line data to document virus prevention and control measures.</P>

Propofol Inhibits Platelet-derived Growth Factor-stimulated Migration in Rat Aortic Smooth Muscle Cells

Kyu Chang Lee,Keun Sang Lee,Bo Kyung Kim,Jeong Ae Lim,Jai Won Koo,Myeong Jong Lee,Hwan Myung Lee,Chang Kwon Lee,Kyung Jong Won 대한마취과학회 2008 Korean Journal of Anesthesiology Vol.54 No.3

Non-destructive profiling of volatile organic compounds using HS-SPME/GC-MS and its application for the geographical discrimination of white rice

Lim, Dong Kyu,Mo, Changyeun,Lee, Dong-Kyu,Long, Nguyen Phuoc,Lim, Jongguk,Kwon, Sung Won The Journal of Food and Drug Analysis (JFDA), Food 2018 JOURNAL OF FOOD AND DRUG ANALYSIS Vol.26 No.1

<P>The authenticity determination of white rice is crucial to prevent deceptive origin labeling and dishonest trading. However, a non-destructive and comprehensive method for rapidly discriminating the geographical origins of white rice between countries is still lacking. In the current study, we developed a volatile organic compound based geographical discrimination method using headspace solid-phase microextraction coupled to gas chromatography-mass spectrometry (HS-SPME/GC-MS) to discriminate rice samples from Korea and China. A partial least squares discriminant analysis (PLS-DA) model exhibited a good classification of white rice between Korea and China (accuracy = 0.958, goodness of fit = 0.937, goodness of prediction = 0.831, and permutation test p-value = 0.043). Combining the PLS-DA based feature selection with the differentially expressed features from the unpaired t-test and significance analysis of microarrays, 12 discriminatory biomarkers were found. Among them, hexanal and 1-hexanol have been previously known to be associated with the cultivation environment and storage conditions. Other hydrocarbon biomarkers are novel, and their impact on rice production and storage remains to be elucidated. In conclusion, our findings highlight the ability to rapidly discriminate white rice from Korea and China. The developed method maybe useful for the authenticity and quality control of white rice. Copyright (C) 2017, Food and Drug Administration, Taiwan. Published by Elsevier Taiwan LLC.</P>

Experimental observation of nonadiabatic bifurcation dynamics at resonances in the continuum

Lim, Jean Sun,You, Hyun Sik,Kim, So-Yeon,Kim, Sang Kyu Royal Society of Chemistry 2019 Chemical science Vol.10 No.8

<▼1><P>In the strong vibronic state mixing regime, both Herzberg type-I and type-II predissociations coexist and proceed in a competitive way.</P></▼1><▼2><P>The surface crossing of bound and unbound electronic states in multidimensional space often gives rise to resonances in the continuum. This situation happens in the πσ*-mediated photodissociation reaction of 2-fluorothioanisole; optically-bright bound S<SUB>1</SUB> (ππ*) vibrational states of 2-fluorothioanisole are strongly coupled to the optically-dark S<SUB>2</SUB> (πσ*) state, which is repulsive along the S–CH<SUB>3</SUB> elongation coordinate. It is revealed here that the reactive flux prepared at such resonances in the continuum bifurcates into two distinct reaction pathways with totally different dynamics in terms of energy disposal and nonadiabatic transition probability. This indicates that the reactive flux in the Franck–Condon region may either undergo nonadiabatic transition funneling through the conical intersection from the upper adiabat, or follow a low-lying adiabatic path, along which multiple dynamic saddle points may be located. Since 2-fluorothioanisole adopts a nonplanar geometry in the S<SUB>1</SUB> minimum energy, the quasi-degenerate S<SUB>1</SUB>/S<SUB>2</SUB> crossing seam in the nonplanar geometry, which lies well below the planar S<SUB>1</SUB>/S<SUB>2</SUB> conical intersection, is likely responsible for the efficient vibronic coupling, especially in the low S<SUB>1</SUB> internal energy region. As the excitation energy increases, bound-to-continuum coupling is facilitated with the aid of intramolecular vibrational redistribution, along many degrees of freedom spanning the large structural volume. This leads to the rapid domination of the continuum character of the reactive flux. This work reports direct and robust experimental observations of the nonadiabatic bifurcation dynamics of the reactive flux occurring at resonances in the continuum of polyatomic molecules.</P></▼2>

Ganglioside is Important Marker in Osteoblast Differentiation of Adipose-Derived Mesenchymal Stem Cells from Mini-Pig

Sung Youn Heo,Dong Hoon Kwak,Yu Na Seo,Won Seok Ju,Hyun Gyu Lim,Seo Yi Lee,Ji-Su Kim,Kyu-Tae Chang,Young-Kug Choo 한국당과학회 2016 한국당과학회 학술대회 Vol.2016 No.07

Mesenchymal stem cells can differentiate into multiple lineages depending on their exposure to differing biochemical and biomechanical inductive factors. The Ganglioside is included in biomarker, that are the major component of cytoplasmic cell membranes complex glycosphingolipids, and play a role in the control of biological processes. However, role of ganglioside in osteogenesis of mini-pig adipose derived mesenchymal stem cells (AD-MSCs) unclear . We have knocked down was ganglioside synthase UDP-glucose ceramide glucosyltransferase (UGCG)using a siRNA differentiation into osteoblast was markedly decreased in UGCG-knocked down AD-MSCs. The results showed significant inhibits alkaline phosphatase, osteocalcin, osteopontin, and Runt-related transcription factor 2 in UGCG knock down AD-MSCs compared to with the control AD-MSCs. Thus we guess, maybe ganglioside is essential factor to stimulate osteogenesis in AD-MSCs.

Simultaneous Profiling of Lysoglycerophospholipids in Rice (<i>Oryza sativa</i> L.) Using Direct Infusion-Tandem Mass Spectrometry with Multiple Reaction Monitoring

Lim, Dong Kyu,Mo, Changyeun,Long, Nguyen Phuoc,Kim, Giyoung,Kwon, Sung Won American Chemical Society 2017 Journal of agricultural and food chemistry Vol.65 No.12

<P>White rice is the final product after the hull and bran layers have been removed during the milling process. Although lysoglycerophospholipids (lysoGPLs) only occupy a small proportion in white rice, they are essential for evaluating rice authenticity and quality. In this study, we developed a high-throughput and targeted lipidomics approach that involved direct infusion-tandem mass spectrometry with multiple reaction monitoring to simultaneously profile lysoGPLs in white rice. The method is capable of characterizing 17 lysoGPLs within 1 min. In addition, unsupervised and supervised analyses exhibited a considerably large diversity of lysoGPL concentrations in white rice from different origins. In particular, a classification model was built using identified lysoGPLs that can differentiate white rice from Korea, China, and Japan. Among the discriminatory lysoGPLs, for the lysoPE(16:0) and lysoPE(18:2) compositions, there were relatively small within-group variations, and they were considerably different among the three countries. In conclusion, our proposed method provides a rapid, high-throughput, and comprehensive format for profiling lysoGPLs in rice samples.</P>