End-of-life vehicles (ELV) have become a global concern as automobiles have become popular worldwide. An international workshop was held to gather data and to discuss 3R policies and ELV recycling systems, their background and present situation, outcomes of related policies and programs, the framework of recycling and waste management, and case studies on related topics in several countries and regions, as well as the essential points of the comparison. Legislative ELV recycling systems are established in the EU, Japan, Korea, and China, while in the US, ELV recycling is managed under existing laws on environmental protection. Since automobile shredding residue (ASR) has a high calorific value and ash content, and includes heavy metals as well as a mass of unclassified fine particles, recycling ASR is considered highly difficult. Countries with a legislative ELV system commonly set a target for recovery rates, with many aiming for more than 95 % recovery. In order to reach this target, higher efficiency in ASR recovery is needed, in addition to material recycling of collectable components and metals. Environmentally friendly design was considered necessary at the planning and manufacturing stages, and the development of recycling systems and techniques in line with these changes are required for sound ELV management.
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BackgroundMethotrexate (MTX) is currently the anchor drug widely used worldwide in the treatment of rheumatoid arthritis (RA). However, the therapeutic response to MTX has been shown to vary widely among individuals, genders and ethnic groups. The reason for this has been not clarified but it is considered to be partially due to several mechanisms in the cellular pathway of MTX including single-nucleotide polymorphisms (SNPs). The purpose of this study was to investigate the allelic frequencies in different ethnic and/or population groups in the 10 polymorphisms of enzyme proteins and transporters related to the MTX response and pharmacokinetics including MTHFR, TYMS, RFC1, FPGS, GGH, ABCB1, ABCC2 and ABCG2 in unrelated healthy Japanese adults and patients with RA.MethodsTen polymorphisms, methylenetetrahydrofolate reductase (MTHFR) 1298, thymidylate synthase (TYMS) 3'-UTR, reduced folate carrier 1 (RFC1) 80 and−43, folypolyglutamyl synthase (FPGS) 1994, γ-glutamyl hydrolase (GGH) 452 and−401, the ABC transporters (ABCB1 3435, ABCC2 IVS23 + 56, ABCG2 914) of enzyme proteins and transporters related to MTX response and pharmacokinetics in 299 unrelated healthy Japanese adults and 159 Japanese patients with RA were investigated to clarify their contributions to individual variations in response and safety to MTX and establish personalized MTX therapy. SNPs were evaluated using real-time polymerase chain reaction (PCR).ResultsComparison of allelic frequencies in our study with other ethnic/population groups of healthy adults and RA patients showed significant differences in 10 polymorphisms among healthy adults and 7 among RA patients. Allelic frequencies of MTHFR 1298 C, FPGS 1994A and ABCB1 3435 T were lower in Japanese than in Caucasian populations and those of ABCC2 IVS23 + 56 C and ABCG2 914A were higher in Japanese than in Caucasian/European populations in both healthy adults and RA patients. Allelic frequencies of MTHFR 1298 C, GGH−401 T, ABCB1 3435 T, and ABCG2 914A were higher in healthy Japanese adults than in an African population, and those of RFC1 80A, RFC1−43C and ABCC2 IVS23 + 56 C in healthy Japanese adults were lower than in Africans. However, no significant differences were seen in the distribution of allelic frequencies between healthy Japanese adults and RA patients.ConclusionThe variations in allelic frequencies in different ethnic and/or population groups in healthy adults and RA patients may contribute to individual variations in MTX response and toxicity.
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