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Synthesis of 6-Alkyloxyl-3,4-dihydro-2(1H)-quinoliones and Their Anticonvulsant Activities

  • Quan, Zhe Shan;Wang, Jun-Min;Rho, Jung-Rae;Kwak, Kyung-Chell;Kang, Hee-Cheol;Jun, Chang-Soo;Chai, Kyu-Yun
    • Bulletin of the Korean Chemical Society
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    • v.26 no.11
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    • pp.1757-1760
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    • 2005
  • A series of 6-alkyloxyl-3,4-dihydro-2(1H)-quinoliones (5a-5n) were synthesized through nitration, reduction, diazotization, hydrolysis and alkylation from 3,4-dihydro-2(1H)-quinolione. Their structures were characterized by IR, $^1H$-NMR and MS. The anticonvulsant activity was evaluated by the Maximal electroshock test (MES) and the subcutaneous pentylenetetrazole (Metrazole) test (sc-Met). The neurotoxicity was measured by the Rotarod test (Tox). The result showed that 6-hexyloxy-3,4-dihydro-2 (1H)-quinolinone (5c) was potent in anti-MES and anti-scMet test with $ED_{50}$ of 24.0 mg/kg and 21.2 mg/kg, respectively, albeit its $TD_{50}$ (67.6 mg/kg) revealed the high neurotoxicity. 6-Benzyloxy-3,4-dihydro-2(1H)-quinolinone (5f) was less effective against MES induced seizure with $ED_{50}$ of 29.6 mg/kg, but no neurotoxicity was observed even under 300 mg/kg. Its Protective index (PI) was greater than 10 preferable to Phenytoin, Carbamazepin, Phenobarbital and Valproate.

Investigation of Ingredients and Hazardous Substances in Disinfectants Used against COVID-19 and Some Livestock Diseases (코로나바이러스감염증-19와 일부 가축전염병 방역소독제품의 함유성분 및 유해물질 조사)

  • Kim, DongHyun;Lim, Miyoung;Lee, Kiyoung
    • Journal of Environmental Health Sciences
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    • v.46 no.4
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    • pp.470-479
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    • 2020
  • Objectives: The Coronavirus Disease 2019 (COVID-19) pandemic has caused the death of 740,000 people around the world as of August 12, 2020. Foot-and-Mouth Disease, Avian Influenza, and African Swine Fever are serious livestock diseases. Government agencies in Korea have provided ingredient information and usage instructions for disinfectants used to counter those infectious diseases. The purpose of this study was to provide information on the chemical ingredients in disinfectant products used against COVID-19 and certain livestock diseases. Methods: We collected information from the Korean government. The Central Disaster Management Headquarters and Central Disease Control Headquarters provided information on disinfectant products used against COVID-19. The Animal and Plant Quarantine Agency of Korea provided information on efficacy-certified disinfectant products for use against selected livestock diseases. Health hazard and environmental hazard information on the ingredients in the disinfectants was collected from the Korea Occupational Safety & Health Agency's Material Safety Data Sheets, and toxicity value information was collected from United States Environmental Protection Agency's CompTox Chemicals Dashboard. Results: There were 76 COVID-19 disinfectant products in use, and the most common ingredients were benzalkonium chloride (51%), alkylbenzyl dimethyl ammonium (30%), and ethanol (3%). There were 216 livestock disease disinfectant products comprised of 89 acidic, 88 oxidic, 30 aldehydic, three alkaline, and six other products. Among the 49 active ingredients used in the disinfectants that were investigated, health and environmental hazard information was provided for many of them, but only 20 chemicals had official toxicological information. Conclusion: Since the disinfectants included numerous chemicals, an understanding of their chemical characteristics could be critical to prevent unintended human or environmental exposure.

Multiple Linkage Disequilibrium Mapping Methods to Validate Additive Quantitative Trait Loci in Korean Native Cattle (Hanwoo)

  • Li, Yi;Kim, Jong-Joo
    • Asian-Australasian Journal of Animal Sciences
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    • v.28 no.7
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    • pp.926-935
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    • 2015
  • The efficiency of genome-wide association analysis (GWAS) depends on power of detection for quantitative trait loci (QTL) and precision for QTL mapping. In this study, three different strategies for GWAS were applied to detect QTL for carcass quality traits in the Korean cattle, Hanwoo; a linkage disequilibrium single locus regression method (LDRM), a combined linkage and linkage disequilibrium analysis (LDLA) and a $BayesC{\pi}$ approach. The phenotypes of 486 steers were collected for weaning weight (WWT), yearling weight (YWT), carcass weight (CWT), backfat thickness (BFT), longissimus dorsi muscle area, and marbling score (Marb). Also the genotype data for the steers and their sires were scored with the Illumina bovine 50K single nucleotide polymorphism (SNP) chips. For the two former GWAS methods, threshold values were set at false discovery rate <0.01 on a chromosome-wide level, while a cut-off threshold value was set in the latter model, such that the top five windows, each of which comprised 10 adjacent SNPs, were chosen with significant variation for the phenotype. Four major additive QTL from these three methods had high concordance found in 64.1 to 64.9Mb for Bos taurus autosome (BTA) 7 for WWT, 24.3 to 25.4Mb for BTA14 for CWT, 0.5 to 1.5Mb for BTA6 for BFT and 26.3 to 33.4Mb for BTA29 for BFT. Several candidate genes (i.e. glutamate receptor, ionotropic, ampa 1 [GRIA1], family with sequence similarity 110, member B [FAM110B], and thymocyte selection-associated high mobility group box [TOX]) may be identified close to these QTL. Our result suggests that the use of different linkage disequilibrium mapping approaches can provide more reliable chromosome regions to further pinpoint DNA makers or causative genes in these regions.

Synthesis of 8-Alkoxy-4,5-dihydro-[1,2,4]triazole[4,3-a]quinoline-1-ones and Evaluation of their Anticonvulsant Properties

  • Sun, Xian-Yu;Jin, Yun-Zhe;Li, Fu-Nan;Li, Gao;Chai, Kyu-Yun;Quan, Zhe-Shan
    • Archives of Pharmacal Research
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    • v.29 no.12
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    • pp.1080-1085
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    • 2006
  • A series of 8-alkoxy-4,5-dihydro-[1,2,4]triazole[4,3-a]quinoline-1-one derivatives were synthesized using 7-hydroxy-3,4-dihydro-2(1H)-quinolone as the starting material. Their anticonvulsant activities were evaluated by the maximal electroshock test (MES) and the subcutaneous pentylenetetrazole test (sc-PTZ), and their neurotoxicities were measured by the rotarod neurotoxicity test (Tox). The tests demonstrated that 8-hexyloxy-4,5-dihydro-[1.2.4]triazole[4.3-a]quinoline-1-one (4e) and 8-heptyloxy-4,5-dihydro-[1,2,4]triazole[4, 3-a]quinoline-1-one (4f) were the most potent anticonvulsants, with 4e having $ED_{50}$ values of 17.17 mg/kg and 24.55 mg/kg and protective index ($PI=TD_{50}/ED_{50}$) values of 41.9 and 29.3 in the MES and sc-PTZ tests, respectively, and 4f having $ED_{50}$ values of 19.7 mg/kg and 21.2 mg/kg and PI values of 36.5 and 33.9 in the MES and sc-PTZ tests, respectively. The PI values of 4e and 4f were many fold better than that of the marketed drugs phenytoin, carbamazepine, phenobarbital and valproate, which have PI values in the range of 1.6-8.1 in the MES test and <0.22-5.2 in the sc-PTZ test. Structure-activity relationships were also discussed.

A Gene-Tagging System for Monitoring of Xanthomonas Species

  • Song, Wan-Yeon;Steven W. Hutcheson;Efs;Norman W. Schaad
    • The Plant Pathology Journal
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    • v.15 no.3
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    • pp.137-143
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    • 1999
  • A novel chromosomal gene tagging technique using a specific fragment of the fatty acid desaturase-like open reading frame (des-like ORF) from the tox-argK gene cluster of Pseudomonas syringae pv. phaseolicola was developed to identify Xanthomonas spp.released into the environment as biocontrol agents. X. campestris pv. convolvuli FB-635, a pathogen of Convolvulus arvensis L., (bindweed), was chosen as the organism in which to develop and test the system. A 0.52 kb DES fragment amplified from P. syringae pv. phaseolicola C-199 was inserted into pGX15, a cosmid clone containing a 10.3 kb Eco RI-HindIII fragment derived from the xanthomonadin biosynthetic gene cluster contained in plasmid pIG102, to create a pigG::DES insertion. The 10.8 kb EcoRI-BamHI fragment carrying the pigG:: DES insertion was cloned into pLAFR3 to generate pLXP22. pLXP22 was then conjugated into X. campestris pv. convolvuli FB-635 and the pigG::DES insertion integrated into the bacterial chromosome by marker exchange. Rifampicin resistant, tetracycline sensitive, starch hydrolyzing, white colonies were used to differentiate the marked strain from yellow pigmented wild-type ones. PCR primers specific for the unique DES fragment were used for direct detection of the marked strain. Result showed the marked strain could be detected at very low levels even in the presence of high levels of other closely related or competitive bacteria. This PCR-based DES-tagging system provides a rapid and specific tool for directly monitoring the dispersal and persistence of Xanthomonas spp.released into the environment.

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A Study on Comparison of Risk Estimates Among Various Exposure Scenario of Several Volatile Organic Compounds in Tap Water (음용수중 휘발성 유기오염물질의 노출경로에 따른 위해도 추정치 비교연구)

  • Chung, Yong;Shin, Dong-Chun;Kim, Jong-Man;Yang, Ji-Yeon;Park, Seong-Eun
    • Environmental Analysis Health and Toxicology
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    • v.10 no.1_2
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    • pp.21-35
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    • 1995
  • Risk assessment processes, which include processes for the estimation of human cancer potency using animal bioassay data and calculation of human exposure, entail uncertainties. In the exposure assessment process, exposure scenarios with various assumptions could affect the exposure amount and excess cancer risk. We compared risk estimates among various exposure scenarios of vinyl chloride, trichloroethylene and tetrachloroethylene in tap water. The contaminant concentrations were analyzed from tap water samples in Seoul from 1993 to 1994. The oral and inhalation cancer potencies of the contaminants were estimated using multistage, Weibull, lognormal, and Mantel-Bryan model in TOX-RISK computer software. In the first case, human excess cancer risk was estimated by the US EPA method used to set the MCL(maximum contaminant level). In the second and third case, the risk was estimated for multi-route exposure with and without adopting Monte-Carlo simulation, respectively. In the second case, exposure input parameters and cancer potencies used probability distributions, and in the third case, those values used point estimates(mean, and maximum or 95% upper-bound value). As a result, while the excess cancer risk estimated by US EPA method considering only direct ingestion tended to be underestimated, the risk which was estimated by considering multi-route exposure without Monte-Carlo simulation and then using the maximum or 95% upper-bound value as input parameters tended to be overestimated. In risk assessment for volatile organic compounds, considering multi-route exposure with adopting Monte-Carlo analysis seems to provide the most reasonable estimations.

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Availability of Toxicologic Screening Tests in the Emergency Department (응급센터에서 시행하는 약물선별현장검사의 유용성)

  • Um, In-Kyung;Park, Jong-Su;Han, Kap-Su;Cho, Han-Jin;Choi, Sung-Hyuck;Lee, Sung-Woo;Hong, Yun-Sik
    • Journal of The Korean Society of Clinical Toxicology
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    • v.9 no.1
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    • pp.26-29
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    • 2011
  • Purpose: The role of a point of care test (POCT) is currently becoming important when treating patients and making decisions in the emergency department. It also plays a role for managing patients presenting with drug intoxication. But the availability of the test has not yet been studied in Korea. Therefore, we investigated the utility and the availability of POCT for drug screening used in the emergency department. Methods: This was a retrospective study for those patients with drug intoxication between January 2007 and December 2010 in an urban emergency department. Results: Between the study period, 543 patients were examined with a Triage$^{(R)}$-TOX Drug Screen. Among those, 248 (45.7%) patients showed negative results and 295 (54.3%) patients showed positive results. The sensitivity of the test for benzodiazepine, acetaminophen and tricyclic antidepressants were 85.9%, 100%, 79.2%, respectively. Conclusion: POCT of drug screening in emergency department showed good accuracy especially in patient with benzodiazepine, acetaminophen and tricyclic antidepressant intoxication. Therefore, it can be useful diagnostic tool for the management of intoxicated patients.

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Salmonella Invasion Gene Regulation: A Story of Environmental Awareness

  • Jones Bradley D.
    • Journal of Microbiology
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    • v.43 no.spc1
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    • pp.110-117
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    • 2005
  • Salmonella enterica serovar Typhimurium causes human gastroenteritis and a systemic typhoid-like infection in mice. A critical virulence determinant of Salmonella is the ability to invade mammalian cells. The expression of genes required for invasion is tightly regulated by environmental conditions and a variety of regulatory genes. The hilA regulator encodes an OmpR/ToxR family transcriptional regulator that activates the expression of invasion genes in response to both environmental and genetic regulatory factors. Work from several laboratories has highlighted that regulation of hilA expression is a key point for controlling expression of the invasive phenotype. A number of positive regulators of hilA expression have been identified including csrAB, sirA/barA, pstS, hilC/sirC/sprA, fis, and hilD. HilD, an AraC/XylS type transcriptional regulator, is of particular importance as a mutation in hilD results in a 14-fold decrease in chromosomal hilA::Tn5lacZY-080 expression and a 53-fold decrease in invasion of HEp-2 cells. It is believed that HilD directly regulates hilA expression as it has been shown to bind to hilA promoter sequences. In addition, our research group, and others, have identified genes (hilE, hha, pag, and lon) that negatively affect hilA transcription. HilE appears to be an important Salmonella-specific regulator that plays a critical role in inactivating hilA expression. Recent work in our lab has been directed at understanding how environmental signals that affect hilA expression may be processed through a hilE pathway to modulate expression of hilA and the invasive phenotype. The current understanding of this complex regulatory system is reviewed.

Dynamics of Microalgae Along the Coastal Areas of Sooyoung Bay, Busan, South Korea

  • Prasad, Binod;Thiyam, General;Lee, Dong-Gyu;Kim, Moo-Sang;Cho, Man-Gi
    • Journal of Marine Bioscience and Biotechnology
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    • v.5 no.4
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    • pp.40-45
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    • 2011
  • Microalgae are one of the major, sustaining components of ecosystem processes and are responsible for biogeochemical reactions that drive our climate changes. Despite this, many marine microalgae are poorly described and little is known of their abundance and distribution along the coastal areas of Sooyoung Bay, Busan, South Korea. The present study has been conducted from November, 2011 to August, 2009 with the objective to provide an overview of the taxonomy diversity and abundance of microalgae along the coastal areas of the Sooyoung Bay. Water samples were collected from different sites, which were located by using a GPS tracker. Chlorophyll fluorescence of the water samples were measured by using ToxY-PAM dual-channel yield analyzer. The chlorophyll fluorescence values were relatively higher during the spring and summer and even in the region near to the sea port. Similarly the abundance of microalgae was higher near the port but diversity index had lower values. The temperature and pH values were same at all the sites. However, only the temperature varied during the sampling period, with higher values during summer and lower in winter. From the preliminary results, the following class of microalgae were found; Bacillariophyceae, Dinophyceae, Silicoflagellate and Cryptophyceae. With a future ongoing work, microalgae are being isolated to establish single cell culture and for identification using light microscopic observations, photography and molecular approaches.

Availability of urine toxicologic screening tests in the emergency department: focused on illegal drugs (응급실에서 시행한 소변 독성 검사의 유용성: 마약을 중심으로)

  • Lee, Se Kyu;Choi, Sangchun
    • Journal of The Korean Society of Clinical Toxicology
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    • v.19 no.1
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    • pp.24-30
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    • 2021
  • Purpose: In Korea, it is predicted that the proportion of drug abusers among patients visiting the emergency room will soon increase. Several emergency medical institutions in Korea are conducting field urine screening tests for poisoning. In this study, we investigated the characteristics and usefulness of urine toxicology screening tests. Methods: The medical records of patients with positive results for tetrahydrocannabinol and methamphetamine from urine toxicology screening tests at a tertiary university hospital from August 2016 to August 2019 were reviewed retrospectively. The subjects were classified into positive and false-positive groups, and their clinical characteristics were compared and analyzed. Results: Of the 2,026 patients surveyed, 823 patients (40.6%) tested positive for one or more drugs. Among them, 12 cases (0.6%) were positive for methamphetamine and 40 cases (2.0%) were positive for tetrahydrocannabinol. The positive and the false-positive rates for methamphetamine were 66.7% and 33.3%, respectively. The positive and the false-positive rates for tetrahydrocannabinol were 2.5% and 97.5%, respectively. Conclusion: Methamphetamine showed a relatively low false-positive rate in our study. Therefore, this test seemed to assist in diagnosing methamphetamine poisoning when considered together with the present illness and physical examination results. On the other hand, the high false-positive rate for tetrahydrocannabinol tests indicates that this test was unlikely to assist in diagnosing tetrahydrocannabinol poisoning. However, considering the growing trend of illegal drug abusers in Korea, it may still be useful as a diagnostic tool for identifying drug users.