A Delphi Study on National Public Vaccine Research and Development Policy in Korea / 보건행정학회지

Vaccination is the most powerful and useful preparation against infectious diseases. However, developing vaccines costs a lot and requires extensive long-term efforts. Therefore, the government should research and develop vaccines with a national-level policy. To greatly enhance the success rate of vaccine development, the policy should be set up considering priorities such as the current status of domestic research, the importance for public health, the urgency of research. The Delphi technique was utilized to draft this survey, through a brainstorming stage, then two inquiries, and finally the final panel meeting where unresolved items were discussed, to draw the conclusion. Among the results, firstly, the highest ranked item on centralized fields for vaccine development by the Ministry of Health was 'self-sufficiency of vaccines.' Secondly, 'emerging infectious disease' was most highly ranked in prioritized fields of vaccine development and research. Thirdly, for the vaccine that needs to be improved and developed further by the government to improve its efficacy and safety, BCG (Bacille de Calmette) for tuberculosis was ranked the highest on both types (intradermal and subcutaneous injection) from National Immunization Programme (NIP) and non-NIP. As for the high risk pathogens, 'anthrax' and 'smallpox' were first and second, consecutively. Lastly, 'development and control of vaccine candidates' was ranked the highest for the area in need for technique development in order to improve domestic vaccine's research level. The results of this study will be put to good use as basic data for the national vaccine research and development (R&D) policy of the country. This study was first step and more studies should be carried out for the final decision of the national vaccine R&D priority.

Clinical and psychological characteristics of propofol abusers in Korea: a survey of propofol abuse in 38, non-healthcare professionals / 대한마취과학회지

BACKGROUND: The aim of this study is to investigate the characteristics of propofol abuse based on the results of a survey analysis of abusers among non-healthcare professionals in Korea. METHODS: Thirty-eight propofol abusers were questioned between October and December 2010, and were enrolled and voluntarily participated in a structured survey consisting of an interview and completing a previously prepared questionnaire. The questionnaire was divided into three distinct parts: part 1 dealt with the history of propofol abuse; part 2 highlighted the problems caused by propofol abuse; and part 3 enquired regarding demographics of abusers. RESULTS: Thirty-one (81.6%) of the 38 interviewees abused propofol for more than one year. During the last 12 months, 34 (89.0%) received propofol at two or three times a week. The minimum and maximum amounts of propofol (median, range) administered each time were 500 (100, 1000) and 2000 (500, 4000) mg, respectively. Stress relief and the maintenance of a sense of well-being were quoted the most important reasons for the first-time administration of propofol and its subsequent abuse, respectively. The majority of abusers (36.0, 97.3%) reported a sense of pleasure or euphoria at the time of their propofol injection. Withdrawal symptoms occurred in five abusers (13.2%). Thirteen (36.1%) reported disruptions in their work life. None of the respondents had previously admitted to and or reported abuse of any other controlled substances. CONCLUSIONS: These results provided reference data for the regulation of propofol in Korea as a controlled substance and may also be of interest to international agencies in other countries.

Comprehensive Variant Screening of the UGT Gene Family

PURPOSE: UGT1A1, UGT2B7, and UGT2B15 are well-known pharmacogenes that belong to the uridine diphosphate glucuronyltransferase gene family. For personalized drug treatment, it is important to study differences in the frequency of core markers across various ethnic groups. Accordingly, we screened single nucleotide polymorphisms (SNPs) of these three genes and analyzed differences in their frequency among five ethnic groups, as well as attempted to predict the function of novel SNPs. MATERIALS AND METHODS: We directly sequenced 288 subjects consisting of 96 Korean, 48 Japanese, 48 Han Chinese, 48 African American, and 48 European American subjects. Subsequently, we analyzed genetic variability, linkage disequilibrium (LD) structures and ethnic differences for each gene. We also conducted in silico analysis to predict the function of novel SNPs. RESULTS: A total of 87 SNPs were detected, with seven pharmacogenetic core SNPs and 31 novel SNPs. We observed that the frequencies of UGT1A1 *6 (rs4148323), UGT1A1 *60 (rs4124874), UGT1A1 *93 (rs10929302), UGT2B7 *2 (rs7439366), a part of UGT2B7 *3 (rs12233719), and UGT2B15 *2 (rs1902023) were different between Asian and other ethnic groups. Additional in silico analysis results showed that two novel promoter SNPs of UGT1A1 -690G>A and -689A>C were found to potentially change transcription factor binding sites. Moreover, 673G>A (UGT2B7), 2552T>C, and 23269C>T (both SNPs from UGT2B15) changed amino acid properties, which could cause structural deformation. CONCLUSION: Findings from the present study would be valuable for further studies on pharmacogenetic studies of personalized medicine and drug response.

Screening of Dihydropyrimidine Dehydrogenase Genetic Variants by Direct Sequencing in Different Ethnic Groups

Dihydropyrimidine dehydrogenase (DPYD) is an enzyme that regulates the rate-limiting step in pyrimidine metabolism, especially catabolism of fluorouracil, a chemotherapeutic agent for cancer. In order to determine the genetic distribution of DPYD, we directly sequenced 288 subjects from five ethnic groups (96 Koreans, 48 Japanese, 48 Han Chinese, 48 African Americans, and 48 European Americans). As a result, 56 polymorphisms were observed, including 6 core polymorphisms and 18 novel polymorphisms. Allele frequencies were nearly the same across the Asian populations, Korean, Han Chinese and Japanese, whereas several SNPs showed different genetic distributions between Asians and other ethnic populations (African American and European American). Additional in silico analysis was performed to predict the function of novel SNPs. One nonsynonymous SNP (+199381A > G, Asn151Asp) was predicted to change its polarity of amino acid (Asn, neutral to Asp, negative). These findings would be valuable for further research, including pharmacogenetic and drug responses studies.

Screening of Dihydropyrimidine Dehydrogenase Genetic Variants by Direct Sequencing in Different Ethnic Groups

Dihydropyrimidine dehydrogenase (DPYD) is an enzyme that regulates the rate-limiting step in pyrimidine metabolism, especially catabolism of fluorouracil, a chemotherapeutic agent for cancer. In order to determine the genetic distribution of DPYD, we directly sequenced 288 subjects from five ethnic groups (96 Koreans, 48 Japanese, 48 Han Chinese, 48 African Americans, and 48 European Americans). As a result, 56 polymorphisms were observed, including 6 core polymorphisms and 18 novel polymorphisms. Allele frequencies were nearly the same across the Asian populations, Korean, Han Chinese and Japanese, whereas several SNPs showed different genetic distributions between Asians and other ethnic populations (African American and European American). Additional in silico analysis was performed to predict the function of novel SNPs. One nonsynonymous SNP (+199381A > G, Asn151Asp) was predicted to change its polarity of amino acid (Asn, neutral to Asp, negative). These findings would be valuable for further research, including pharmacogenetic and drug responses studies.

Screening of Genetic Polymorphisms of CYP3A4 and CYP3A5 Genes

Given the CYP3A4 and CYP3A5's impact on the efficacy of drugs, the genetic backgrounds of individuals and populations are regarded as an important factor to be considered in the prescription of personalized medicine. However, genetic studies with Korean population are relatively scarce compared to those with other populations. In this study, we aimed to identify CYP3A4/5 polymorphisms and compare the genotype distributions among five ethnicities. To identify CYP3A4/5 SNPs, we first performed direct sequencing with 288 DNA samples which consisted of 96 Koreans, 48 European-Americans, 48 African-Americans, 48 Han Chinese, and 48 Japanese. The direct sequencing identified 15 novel SNPs, as well as 42 known polymorphisms. We defined the genotype distributions, and compared the allele frequencies among five ethnicities. The results showed that minor allele frequencies of Korean population were similar with those of the Japanese and Han Chinese populations, whereas there were distinct differences from European-Americans or African-Americans. Among the pharmacogenetic markers, frequencies of CYP3A4*1B (rs2740574) and CYP3A5*3C (rs776742) in Asian groups were different from those in other populations. In addition, minor allele frequency of CYP3A4*18 (rs28371759) was the highest in Korean population. Additional in silico analysis predicted that two novel non-synonymous SNPs in CYP3A5 (+27256C>T, P389S and +31546T>G, I488S) could alter protein structure. The frequency distributions of the identified polymorphisms in the present study may contribute to the expansion of pharmacogenetic knowledge.

Estrogen receptor independent neurotoxic mechanism of bisphenol A, an environmental estrogen

Bisphenol A (BPA), a ubiquitous environmental contaminant, has been shown to cause developmental toxicity and carcinogenic effects. BPA may have physiological activity through estrogen receptor (ER) -alpha and -beta, which are expressed in the central nervous system. We previously found that exposure of BPA to immature mice resulted in behavioral alternation, suggesting that overexposure of BPA could be neurotoxic. In this study, we further investigated the molecular neurotoxic mechanisms of BPA. BPA increased vulnerability (decrease of cell viability and differentiation, and increase of apoptotic cell death) of undifferentiated PC12 cells and cortical neuronal cells isolated from gestation 18 day rat embryos in a concentration-dependent manner (more than 50 micrometer). The ER antagonists, ICI 182,780, and tamoxifen, did not block these effects. The cell vulnerability against BPA was not significantly different in the PC12 cells overexpressing ER-alpha and ER-beta compared with PC12 cells expressing vector alone. In addition, there was no difference observed between BPA and 17-beta estradiol, a well-known agonist of ER receptor in the induction of neurotoxic responses. Further study of the mechanism showed that BPA significantly activated extracellular signal-regulated kinase (ERK) but inhibited anti-apoptotic nuclear factor kappa B (NF-kappaB) activation. In addition, ERK-specific inhibitor, PD 98,059, reversed BPA-induced cell death and restored NF-kappaB activity. This study demonstrated that exposure to BPA can cause neuronal cell death which may eventually be related with behavioral alternation in vivo. However, this neurotoxic effect may not be directly mediated through an ER receptor, as an ERK/NF-kappaB pathway may be more closely involved in BPA-induced neuronal toxicity.