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In Vitro Metabolism of a New Neuroprotective Agent, KR-31543 in the Human Liver Microsomes : Identification of Human Cytochrome P450

  • Ji, Hye-Young;Lee, Seung-Seok;Yoo, Sung-Eun;Kim, Hosoon;Lee, Dong-Ha;Lim, Hong;Lee, Hye-Suk
    • Archives of Pharmacal Research
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    • v.27 no.2
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    • pp.239-245
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    • 2004
  • KR-31543, (2S,3R,4S)-6-amino-4-[N-(4-chlorophenyl)-N-(2 -methyl-2H-tetrazol-5-ylmethyl) amino]-3,4-dihydro-2-dimethoxymethyl-3-hydroxy-2-methyl-2H-1-benzopyran, is a new neuroprotective agent for preventing ischemia-reperfusion damage. This study was performed to identify the metabolic pathway of KR-31543 in human liver microsomes and to characterize cytochrome P450 (CYP) enzymes that are involved in the metabolism of KR-31543. Human liver microsomal incubation of KR-31543 in the presence of NADPH resulted in the formation of two metabolites, M1 and M2. M1 was identified as N-(4-chlorophenyl)-N-(2-methyl-2H-tetrazol-5-ylmethyl)amine on the basis of LC/MS/MS analysis with a synthesized authentic standard, and M2 was suggested to be hydroxy-KR-31543. Correlation analysis between the known CYP enzyme activities and the rates of the formation of M 1 and M2 in the 12 human liver microsomes have showed significant correlations with testosterone 6$\beta$-hydroxylase activity (a marker of CYP3A4). Ketoconazole, a selective inhibitor of CYP3A4, and anti-CYP3A4 monoclonal antibodies potently inhibited both N-hydrolysis and hydroxylation of KR-31543 in human liver microsomes. These results provide evidence that CYP3A4 is the major isozyme responsible for the metabolism of KR-31543 to M1 and M2.

Chemical Risk Assessment Screening Tool of a Global Chemical Company

  • Tjoe-Nij, Evelyn;Rochin, Christophe;Berne, Nathalie;Sassi, Alessandro;Leplay, Antoine
    • Safety and Health at Work
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    • v.9 no.1
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    • pp.84-94
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    • 2018
  • Background: This paper describes a simple-to-use and reliable screening tool called Critical Task Exposure Screening (CTES), developed by a chemical company. The tool assesses if the exposure to a chemical for a task is likely to be within acceptable levels. Methods: CTES is a Microsoft Excel tool, where the inhalation risk score is calculated by relating the exposure estimate to the corresponding occupational exposure limit (OEL) or occupational exposure band (OEB). The inhalation exposure is estimated for tasks by preassigned ART1.5 activity classes and modifying factors. Results: CTES requires few inputs. The toxicological data, including OELs, OEBs, and vapor pressure are read from a database. Once the substance is selected, the user specifies its concentration and then chooses the task description and its duration. CTES has three outputs that may trigger follow-up: (1) inhalation risk score; (2) identification of the skin hazard with the skin warnings for local and systemic adverse effects; and (3) status for carcinogenic, mutagenic, or reprotoxic effects. Conclusion: The tool provides an effective way to rapidly screen low-concern tasks, and quickly identifies certain tasks involving substances that will need further review with, nevertheless, the appropriate conservatism. This tool shows that the higher-tier ART1.5 inhalation exposure assessment model can be included effectively in a screening tool. After 2 years of worldwide extensive use within the company, CTES is well perceived by the users, including the shop floor management, and it fulfills its target of screening tool.

Useful and Effective Diagnosis and Evaluation Tools for Eenvironmental Change in Increased Mill Water System Closure

  • Linda R. Robertson;Lee, Byung-Tae;Kim, Tae-Joon
    • Journal of Korea Technical Association of The Pulp and Paper Industry
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    • v.33 no.5
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    • pp.1-11
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    • 2001
  • In the past, abundant and clean water was available for paper mills'use. However, the growth of population and industry made water less available nowadays. Also, environmental regulation limits wastewater discharge, which affects mill operation cost. Therefore, paper mills are under pressure to use more recycled water and mill system closure. As a result, chemical and physical parameters of water are changing and new environment if being created for microorganisms in paper mill system as well. The more soluble or suspended organic materials are increased as more water is recycled and less or scarce dissolved oxygen is available, depending on the degree of recycled water usage. Microorganism flora ill paper mill system will be a1so shifted according to the environmental change of mill system. Anaerobic bacteria, including sulfate reducing bacteria (SRB), will be dominant in the system as very low or almost no oxygen available in the system. Nevertheless, it is common in domestic paper mills that employ the same and old biocides as a means of microbial control, and microbiological control is often less recognized or even neglected. The right biocide selection for increased reductive environment of mills is critical for operation and estimated loss from paper quality defects such as sheet break, holes due to microbiological cause is tremendous compared to the microbiological control cost. It is imperative to investigate and diagnosis the environmental change of mills for right control of cumbersome microorganisms. Several useful diagnosis tools, including new technology employing OFM(Optical Fouling Monitor) in situ, are illustrated.

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Analysis of EQ pH Condition and Fission Product Removal Capability for Nuclear Power Plant (원전의 내환경기기검증 화학환경 및 핵분열생성물 제거능력 평가)

  • Song, Dong Soo;Ha, Sang Jun;Seong, Je Joong;Jeon, Hwang Yong;Huh, Seong Cheol
    • Journal of Energy Engineering
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    • v.23 no.3
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    • pp.186-190
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    • 2014
  • Nuclear Power Plants require the control ability of chemical condition (pH) because pH control during transient accident such as LOCA makes an able the fission product removal capability to be maintained, stress corrosion cracking of stainless steel equipment to be prevented and the production of hydrogen by aluminum and zinc to be minimized. An NPP is designed to control the pH of containment spray and sump coolant using the spray additives 30% NaOH in the event of loss of coolant accident. In this paper, the pH of sump coolant of an NPP during LOCA was analyzed and the fission products removal constant and decontamination factor were calculated according to Standard Review Plan 6.5.2 related to spray chemical conditions of pH. The calculated pH value of recirculation mode using the computer code corresponds to 8.09~9.67, which meets the chemical environment regulation requirements. The fission product removal capability caused by containment spray system is performed to provide input to radiation analysis.

POLYPROPYLENE/CLAY NANOCOMPOSITES FOR AUTOMOTIVE APPLICATIONS

  • HONG C. H.;LEE Y. B.;JHO J. Y.;NAM B. U.;HWANG T. W.
    • International Journal of Automotive Technology
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    • v.6 no.6
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    • pp.665-670
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    • 2005
  • Nanocomposites of polypropylene with organically modified clays were compounded on a twin-screw extruder by two-step melt compounding of three components, i.e., polypropylene, maleic anhydride grafted polypropylene (PP-g-MA), and organically modified clay. The effect of PP-g-MA compatibilizers, including PH-200, Epolene-43, Polybond-3002, Polybond-3200, with a wide range of maleic anhydride (MA) content and molecular weight was examined. Morphologies of nanocomposites and their mechanical properties such as stiffness, strength, and impact resistance were investigated. X-ray diffraction patterns showed that the dispersion morphology of clay particles seemed to be determined in the first compounding step and the further dispersion of clays didn't occur in the second compounding step. As the ratio of PP-g-MA to clay increased, the clay particles were dispersed more uniformly in the matrix resin. As the dispersibility of clays was enhanced, the reinforcement effect of the clays increased, however impact resistance decreased.

Improvement Plan of Implementing Condition Assessment in Process Safety Management (PSM) System (공정안전관리(PSM)제도의 이행상태평가 개선방안)

  • Lee, Joo Yeob;Lee, Keun Won;Ahn, Byung Joon;Kim, Tae-Ok
    • Journal of the Korean Society of Safety
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    • v.31 no.4
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    • pp.27-34
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    • 2016
  • Process Safety Management (PSM) system was introduced since 1996 and it makes voluntarily organizing and managing chemical accident prevention system by company itself that contributes to reduce the chemical accidents. However, large or small scaled chemical accidents had occurred frequently in these days. This trend is brought up the necessity to analyze and improve PSM system. In this study, it was conducted by the questionnaire survey and workshop for prevention of major industrial accidents in PSM sites in order to collect extensive opinions from all walks of life and identify overall operation condition. It was proposed to establish improvement plan of implementing condition assessment in PSM system. By results of the study, company's voluntary safety management will be induced by improved PSM system and management plan and it expects to prevent the major industrial accidents.

The Effect of Solution Treatment on Intergranular Corrosion Resistance of a New Type Ultra Low Carbon Stainless Steel

  • Julin, Wang;Nannan, Ni;Qingling, Yan;Lingli, Liu
    • Corrosion Science and Technology
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    • v.6 no.3
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    • pp.140-146
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    • 2007
  • In the paper, with corrosion velocity measurement and metallographic observation on specimens after sulfuric acid/ferric sulfate boiling experiment, intergranular corrosion tendency of the new type ultra low carbon stainless steel developed by ourselves which experienced solution treatment at different temperatures was evaluated. A VHX 500 super depth field tridimensional microscope was used to observe corrosion patterns on the sample surfaces. The depth and width of grain boundary corrosion groove were measured by the tridimensional microscope, which indicated that the corrosion degrees of the samples which received solution treatment at different temperatures are quite different. Transgranular corrosion at different degree occurred along with forged glide lines. After comparison it was proved that the stainless steel treated at $1100^{\circ}C$ performs very well against intergranular corrosion.