Four-Week Repeated Intravenous Dose Toxicity and Toxicokinetic Study of TS-DP2, a Novel Human Granulocyte Colony Stimulating Factor in Rats

Lee, JooBuom,Lee, Kyungsun,Choe, Keunbum,Jung, Hyunseob,Cho, Hyunseok,Choi, Kiseok,Kim, Taegon,Kim, Seojin,Lee, Hyeong-Seok,Cha, Mi-Jin,Song, Si-Whan,Lee, Chul Kyu,Chun, Gie-Taek Korean Society of ToxicologyKorea Environmental Mu 2015 Toxicological Research Vol.31 No.4

TS-DP2 is a recombinant human granulocyte colony stimulating factor (rhG-CSF) manufactured by TS Corporation. We conducted a four-week study of TS-DP2 (test article) in repeated intravenous doses in male and female Sprague-Dawley (SD) rats. Lenograstim was used as a reference article and was administered intravenously at a dose of $1000{\mu}g/kg/day$. Rats received TS-DP2 intravenously at doses of 250, 500, and $1000{\mu}g/kg/day$ once daily for 4 weeks, and evaluated following a 2-week recovery period. Edema in the hind limbs and loss of mean body weight and body weight gain were observed in both the highest dose group of TS-DP2 and the lenograstim group in male rats. Fibro-osseous lesions were observed in the lenograstim group in both sexes, and at all groups of TS-DP2 in males, and at doses of TS-DP2 $500{\mu}g/kg/day$ and higher in females. The lesion was considered a toxicological change. Therefore, bone is the primary toxicological target of TS-DP2. The lowest observed adverse effect level (LOAEL) in males was $250{\mu}g/kg/day$, and no observed adverse effect level (NOAEL) in females was $250{\mu}g/kg/day$ in this study. In the toxicokinetic study, the serum concentrations of G-CSF were maintained until 8 hr after administration. The systemic exposures ($AUC_{0-24h}$ and $C_0$) were not markedly different between male and female rats, between the administration periods, or between TS-DP2 and lenograstim. In conclusion, TS-DP2 shows toxicological similarity to lenograstim over 4-weeks of repeated doses in rats.

Four-Week Repeated Intravenous Dose Toxicity and Toxicokinetic Study of TS-DP2, a Novel Human Granulocyte Colony Stimulating Factor in Rats

JooBuom Lee,Kyungsun Lee,Keunbum Choe,Hyunseob Jung,Hyunseok Cho,Kiseok Choi,Taegon Kim,Seojin Kim,Hyeong-Seok Lee,Mi-Jin Cha,Si-Whan Song,Chul Kyu Lee,Gie-Taek Chun 한국독성학회 2015 Toxicological Research Vol.31 No.4

TS-DP2 is a recombinant human granulocyte colony stimulating factor (rhG-CSF) manufactured by TS Corporation. We conducted a four-week study of TS-DP2 (test article) in repeated intravenous doses in male and female Sprague-Dawley (SD) rats. Lenograstim was used as a reference article and was administered intravenously at a dose of 1000 μg/kg/day. Rats received TS-DP2 intravenously at doses of 250, 500, and 1000 μg/kg/day once daily for 4 weeks, and evaluated following a 2-week recovery period. Edema in the hind limbs and loss of mean body weight and body weight gain were observed in both the highest dose group of TS-DP2 and the lenograstim group in male rats. Fibro-osseous lesions were observed in the lenograstim group in both sexes, and at all groups of TS-DP2 in males, and at doses of TS-DP2 500 μg/kg/day and higher in females. The lesion was considered a toxicological change. Therefore, bone is the primary toxicological target of TS-DP2. The lowest observed adverse effect level (LOAEL) in males was 250 μg/kg/day, and no observed adverse effect level (NOAEL) in females was 250 μg/kg/day in this study. In the toxicokinetic study, the serum concentrations of G-CSF were maintained until 8 hr after administration. The systemic exposures (AUC0-24h and C0) were not markedly different between male and female rats, between the administration periods, or between TS-DP2 and lenograstim. In conclusion, TS-DP2 shows toxicological similarity to lenograstim over 4-weeks of repeated doses in rats.

Groove 형상 오리피스를 적용한 충돌형 인젝터의 모사 젤 추진제 분열특성 연구

이주현(Joohyun Lee),이동희(Donghee Lee),이동근(Donggeun Lee),이인웅(Inwoong Lee),강태곤(Taegon Kang),장석필(Seokpil Jang),문희장(Heejang Moon) 한국추진공학회 2024 한국추진공학회 학술대회논문집 Vol.2024 No.5

Rebinding dynamics of NO to microperoxidase-8 probed by time-resolved vibrational spectroscopy

Lee, Taegon,Kim, Jooyoung,Park, Jaeheung,Pak, Youngshang,Kim, Hyojoon,Lim, Manho The Royal Society of Chemistry 2016 Physical chemistry chemical physics Vol.18 No.7

<P>Femtosecond vibrational spectroscopy was used to probe the rebinding kinetics of NO to microperoxidase-8 (Mp), an ideal model system for the active site of ligand-binding heme proteins, including myoglobin and hemoglobin, after the photodeligation of MpNO in glycerol/water (G/W) solutions at 294 K. The geminate rebinding (GR) of NO to Mp in viscous solutions was highly efficient and ultrafast and negligibly dependent on the solution viscosity, which was adjusted by changing the glycerol content from 65% to 90% by volume in G/W mixtures. The kinetics of the GR of NO to Mp in viscous solutions was well represented by an exponential function with a time constant of ca. 11 ps. Although the kinetic traces of the GR of NO to Mp in solutions with three different viscosities (18, 81, and 252 cP) almost overlap, they show a slight difference early in the decay process. The kinetic traces were also described by the diffusion-controlled reaction theory with a Coulomb potential. Since the ligand is deligated in a neutral form, an ionic pair of NO- and Mp(+) may be produced before forming the Mp-NO bond by an electron transfer from Mp to NO as the deligated NO is sufficiently near to the Fe atom of Mp. The strong reactivity between NO and ferrous heme may arise from the Coulomb interaction between the reacting pair, which is consistent with the harpooning mechanism for NO binding to heme.</P>

Direct Observation of Plasmon-Induced Interfacial Charge Separation in Metal/Semiconductor Hybrid Nanostructures by Measuring Surface Potentials

Lee, Seung-Hoon,Lee, Seung Woo,Oh, Taegon,Petrosko, Sarah Hurst,Mirkin, Chad A.,Jang, Jae-Won American Chemical Society 2018 Nano letters Vol.18 No.1

<P>Plasmon-induced interfacial charge separation (PICS) is one of the key processes responsible for the improved conversion efficiencies of energy-harvesting devices that incorporate metal nanostructures. In this Letter, we reveal a mechanism of PICS by visualizing (with nanometer-scale resolution) and characterizing plasmon-exciton coupling between <I>p</I>-type poly(pyrrole) (PPy) nanowires (NWs) and Ag nanoparticles (NPs) using light-irradiated Kelvin probe force microscopy (KPFM). Under blue-light irradiation, the Ag NPs are expected to donate electrons to the PPy NWs via a hot electron injection process. However, in this Letter, we observe that under blue-light irradiation the plasmonically and excitonically excited electrons in the semiconductor back-transfer to the metal. The PICS in this system can be explained by comparing it with a similar one where Au NPs are attached to <I>n</I>-type ZnO NWs; we observed a net electron transfer from the Au NPs to the ZnO NWs (an upward band bending is formed at the interface of the two materials, presumably obstructing electron back-transfer). Indeed, energy band matching between the metal and the semiconductor components of hybrid nanostructures influences PICS pathways. These experimental findings and our proposed mechanism consistently explain the PICS occurring in the PPy NW-Ag NP system with important implications on explaining their cooperative optoelectronic activities.</P> [FIG OMISSION]</BR>

Efficient direct electron transfer via band alignment in hybrid metal-semiconductor nanostructures toward enhanced photocatalysts

Lee, Seung-Hoon,Lee, Seung Woo,Jeon, Taegon,Park, Dong Hyuk,Jung, Sung Chul,Jang, Jae-Won Elsevier 2019 Nano energy Vol.63 No.-

<P><B>Abstract</B></P> <P>Plasmonic metal nanostructures can improve the photon-charge conversion efficiency in metal/semiconductor hybrid systems through direct electron transfer (DET), resonance energy transfer (RET), and accelerated exciton separation. These enhancement mechanisms of photon-charge conversion have been independently investigated, and it remains unclear which is the most efficient process for the conversion. Herein, DET is proposed as the most efficient pathway due to its ability to facilitate charge separation along with the extended band bending at the interface between the metal and the semiconductor under light irradiation. This investigation on plasmon-induced charge separation was carried out with metal-nanoparticle-decorated <I>p</I>-type semiconductor nanowires by wavelength-tunable light-irradiated Kelvin probe force microscopy and photocurrent measurements. In addition, the band alignment between the metal and the semiconductor was characterized by density functional theory calculations. DET was shown to be superior to RET by an approximated ratio of 8:2 with the coexistence of both plasmonic and excitonic excitations. This observation suggests a straightforward way to develop efficient photocatalysts – engineering individual pathways of plasmon-induced charge separation and transfer.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Efficiency of PICS process in metal-semiconductor nanostructure is investigated with a comparative manner. </LI> <LI> DET more efficiently contributes to PICS than exciton separation and RET. </LI> <LI> DET is superior to RET by an approximated ratio of 8:2 with the coexistence of both plasmonic and excitonic excitations. </LI> <LI> Band alignment with effective charge separation between the metal and semiconductor makes DET more effective than others. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>Plasmonic metal nanostructures can improve the photon-charge conversion efficiency in a metal/semiconductor hybrid system through direct electron transfer (DET), resonance energy transfer (RET), and accelerated exciton separation. Herein, DET is proposed as the most efficient pathway and DET is superior to RET by an approximated ratio of 8:2 with the co-existence of both plasmonic and excitonic excitations.</P> <P>[DISPLAY OMISSION]</P>

Bortezomib pharmacokinetics in tumor response and peripheral neuropathy in multiple myeloma patients receiving bortezomib-containing therapy

Lee, Sung-Eun,Choi, Kyungmee,Han, Seunghoon,Lee, Jongtae,Hong, Taegon,Park, Gab-Jin,Yim, Dong-Seok,Min, Chang-Ki RAPID COMMUNICATIONS OF OXFORD LTD 2017 ANTICANCER DRUGS Vol.28 No.6

<P>The usefulness of pharmacokinetics of bortezomib for multiple myeloma (MM) with respect to the maximum response to bortezomib and bortezomib-induced peripheral neuropathy (BIPN) development was studied. Maximum response to subcutaneous bortezomib therapy and BIPN occurrence for the first 12 weeks of treatment in 35 MM patients treated by bortezomib-dexamethasone (VD) and bortezomib-melphalan-prednisone (VMP) were evaluated. On day 1 of cycle 1, seven whole-blood samples were collected for 3 h after dosing completion to obtain the maximum plasma concentration and area under the time-concentration curve during 3 h postdose (AUC(0-3)) in each patient. A total of 35 patients with complete data were analyzed and the overall response rate was 91.4%. Complete response (CR) was observed in 42.9% patients. The maximum plasma concentration (C-max) was significant for the CR rate in two different models [full model: odds ratio (OR) = 1.092; P = 0.038, final model: OR = 1.081; P = 0.038]. In addition, C-max was associated with a progression-free survival advantage. Overall, 48.6% of patients developed BIPN including peripheral sensory neuropathy and neuralgia. The VMP-treated patients had a higher risk compared with the VD-treated patients (OR = 21.662; P = 0.029). C-max had a tendency to affect the occurrence of BIPN (>= grade 2) (OR = 1.064; P = 0.092). In real-world clinical practice using bortezomib for MM patients, C-max among pharmacokinetic factors significantly affected the achievement of CR. The VMP-treated patients showed vulnerability to BIPN, suggesting the necessity for more careful monitoring. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.</P>

Picosecond Dynamics of Photoexcited DNO-Bound Myoglobin Probed by Femtosecond Vibrational Spectroscopy

Lee, Taegon,Hwang, Sungu,Lim, Manho American Chemical Society 2015 The Journal of physical chemistry B Vol.119 No.5

<P>Like nitric oxide (NO), nitroxyl (HNO), a reduced form of NO, plays many biologically important roles including neurological function and vascular regulation. Although HNO is unstable in aqueous solution, it is exceptionally stable on binding to ferrous myoglobin (Mb) to form MbHNO. Various experimental and theoretical investigations has been carried out to unveil the structure of the active site and binding characteristics of MbHNO that can explain its functioning mechanism and the origin of its unusual stability. However, the binding dynamics of HNO to Mb, as well as the photochemical and photophysical processes associated with binding, have not been fully established. Herein, femtosecond vibrational spectroscopy was used to probe the photoexcitation dynamics of excited MbDNO in D<SUB>2</SUB>O solution at 294 K with a 575 nm pulse. Time-resolved spectra were described by three vibrational bands near 1380 cm<SUP>–1</SUP>, in the expected N–O stretching (ν<SUB>N–O</SUB>) mode of MbDNO, and all three bands showed instantaneous bleach that decays on a picosecond time scale. The three bands were assigned based on isotope shifts upon <SUP>15</SUP>N substitution and <I>ab initio</I> calculation of the vibrational frequency on a DNO-bound model heme. These three bands likely arise from Fermi interactions between the strong ν<SUB>N–O</SUB> mode and the weak overtone and combination modes of the N atom-related modes. The immediate appearance of the bleach in these bands and the picosecond decay of the bleach indicate that most of the photoexcited MbDNO undergoes picosecond geminate rebinding (GR) of DNO to Mb subsequent to its immediate deligation. Ultrafast and efficient GR of DNO likely arises from the bonding structure of the ligand and high reactivity between DNO and Mb.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jpcbfk/2015/jpcbfk.2015.119.issue-5/jp509644m/production/images/medium/jp-2014-09644m_0006.gif'></P>

Dynamics of CO Rebinding to Protoheme in Viscous Solutions

Taegon Lee,박재흥,김주영,주상우,임만호 대한화학회 2009 Bulletin of the Korean Chemical Society Vol.30 No.1

We present the geminate rebinding kinetics measurements of CO to 2-methylimidazole (2-MeIm) bound ferrous protoporphyrin- IX (FePPIX) in alkaline glycerol/water mixtures at 293 K after photolysis. The kinetics was probed by monitoring the CO stretching mode using femtosecond vibrational spectroscopy. When 2-MeIm is used in excess, heme dimers that typically form in low viscosity solutions disappear as the viscosity of the solvent increases. Heme aggregates formed in low viscosity solutions turn monomeric as more 2-MeIm is added, suggesting that 6-coordinated heme, including a strong proximal histidine tends to be in the monomeric form. The vibrational band of CO in the 2-MeIM-FePPIX-CO is well described by a single Gaussian function centered at 1958 cm‐1 and 28 cm‐1 full width at half maximum. The efficiency and rate of the geminate rebinding of CO to the heme increase with viscosity of the solvent, suggesting that retention of the dissociated CO near the heme, for a longer period by the viscous solvent media, accelerates rebinding.

농림수산식품분야 온실가스 인벤토리 관리를 위한 데이터베이스 설계

김태곤 ( Taegon Kim ),배연정 ( Yeonjoung Bae ),이형진 ( Hyungjin Lee ),이성용 ( Sung Yong Lee ),서교 ( Kyo Suh ) 한국농공학회 2012 한국농공학회 학술대회초록집 Vol.2012 No.-

기후변화협약 제 4조 및 12조, 교토의정서에 의하여 온실가스 의무감축국은 국가 온실가스 배출량 산정 및 국가보고서 제출이 의무화되고, 국가 온실가스 인벤토리 시스템을 구축하여 운영하고 있다. 우리나라는 저탄소 녹색성장 기본법 시행령 제36조 4항에 의거하여 각 분야별 온실가스 산정기관은 온실가스 정보 및 통계를 관장하는 온실가스 종합정보센터에 매년 6월에 제출하도록 의무화하였다. 농림수산식품분야의 온실가스 배출원은 산업이나 에너지 분야와 달리비점배출원 형태로 구성되어 있으며, 배출량은 활동량과 배출계수를 곱하여 산정하고 있는데, 활동자료는 국가통계를 이용한다. 비점배출원이기 때문에 직접적인 계측이 어렵고, 산정모델이나 기초데이터가 중요하다. 또한 국가통계가 “1996 IPCC 가이드라인”에서 제시하는 활동자료를 충족시키지 못하며, 배출계수는 가이드라인에서 제시하는 기본값을 이용하고 있어 앞으로 개선이 필요한 실정이다. 본 연구에서는 다양한 활동자료와 배출계수를 효과적으로 관리하여, 1996 IPCC 가이드라인에서 2006 IPCC 가이드라인으로 산정기준 변화에 따른 산정모델 적용, 추가되는 활동자료의 저장 및 배출계수 변화에 대한 이력관리를 도울 수 있도록 온실가스 인벤토리 관리시스템의 데이터베이스를 설계하고자 한다.