• Title/Summary/Keyword: toxic

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Hepatotoxicity of Rifampicin and Pyrazinamide Treatment Excluding Isoniazid (Isoniazid를 제외한 Rifampicin과 Pyrazinamide 병합치료의 간독성 빈도)

  • Choi, Ik Su;Park, I-Nae;Hong, Sang-Bum;Oh, Yeon-Mok;Lim, Chae-Man;Lee, Sang Do;Koh, Younsuck;Kim, Woo Sung;Kim, Dong Soon;Kim, Won Dong;Shim, Tae Sun
    • Tuberculosis and Respiratory Diseases
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    • v.60 no.1
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    • pp.38-43
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    • 2006
  • Background : Even though two-month rifampicin (RMP, R) and pyrazinamide (PZA, P) treatment has some advantages over isoniazid (INH, H) treatment for latent tuberculosis infection (LTBI), it was withdrawn from the list of treatment regimens for LTBI because of reported cases of severe hepatotoxicity. The purpose of this study was to estimate the frequency of hepatotoxicity of RMP and PZA treatment excluding INH in a Korean population. Method : TIn order to recruit patients who were prescribed RMP and PZA excluding INH, 256 INH-resistant tuberculosis patients were investigated through retrospective medical record analysis. A standard four-drug regimen was changed to a RMP/PZA-containing regimen excluding INH in 64 patients (RZ+ group). In the same study period, 146 patients who were prescribed an INH/RMP/PZA-containing standard regimen were randomly selected as a control (HRZ+ group). Clinical characteristics including liver diseases and the frequency of drug-induced hepatitis were compared between the RZ+ and HRZ+ groups. Result : The mean age of patients in the RZ+ group was 50.2 (${\pm}16.2$) and the male-to-female ratio was 36:28. The frequency of underlying liver diseases was 10.9% (7/64), which was not significantly different from that of the HRZ+ group (4.1%, 6/146). Even though the treatment duration of RZ+ ($5.5{\pm}4.8months$) was longer that than that of HRZ+ ($2.7{\pm}2.3months$), the frequency of toxic hepatitis was not significantly different between RZ+ and HRZ+ groups, 3.5% (2/57) and 7.1% (10/140), respectively. Conclusion : Hepatotoxicity was mild and occurred in a minor proportion of patients in a Korean population prescribed an RMP/PZA-containing regimen. A future prospective study including more patients is needed.

Metabolic Responses of Activated Sludge to Pentachlorophenol in a SBR System (SBR 처리 장치에서 활성 슬럿지의 대사에 미치는 Pentachlorophenol의 독성 효과)

  • KIM Sung-Jae;Benefield Larry D.
    • Journal of Aquaculture
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    • v.6 no.4
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    • pp.323-338
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    • 1993
  • The primary objective of this study was to examine the toxic effects of PCP on activated sludge and to analyze its metabolic responses while treating wastewater containing pentachlorophenol (PCP) in a sequencing batch reactor (SBR) system operating under different control strategies. This study was conducted in two phases 1 and 2 (8-hr and 12-hr cycles). Each phase was operated with two control strategies I and II. Strategy I (reactor 1) involved rapid addition (5 minutes to complete) of substrate to the reactor with continuous mixing but no aeration for 2 hours. Strategy II (reactor 2) involved adding the feed continuously during the first 2 hours of the cycle when the system was mixed but not aerated. During both phases each reactor was operated at a sludge age of 15 days. The synthetic wastewater was used as a feed. The COD of the feed solution was about 380 mg/L. After the reference response for both reactors was established, the steady state response of each system was established for PCP feed concentrations of 0.1 mg/L, 1.0 mg/L, and 5.0 mg/L in SBR systems operating on both 8-hr and 12-hr cycles. Soluble COD removal was not inhibited at any feed PCP concentrations used. At 5.0 mg/L feed PCP concentration and in SBR systems operating on phase 2, the concentrations or ML VSS were decreased; selective pressure on the mixed biomass might be increased, narrowing the range of possible ecological responses; the settleability of activated sludge was poor; the SOURs were increased, showing that the systems were shocked. Nitrification was made to some extent at all concentrations of feed PCP in SBR systems operating on phase 2 whereas in SBR systems operating on phase 1 little nitrification was observed. Then, nitrification will be delayed as much as soluble COD removal is retarded due to PCP inhibition effects. Enhanced biological phosphorus removal occurring in the system operating with control strategy I during phase 1 of this work and in the presence of low concentrations of PCP was unreliable and might cease at anytime, whereas enhanced biological phosphorus removal occurring in the system operating with either control strategy I or II during phase 2 of this work and in the presence of feed PCP concentrations up to 1.0 mg/L was reliable. When, however, such processes were exposed to 5.0 mg/L PCP dose, enhanced phosphorus removal ceased and never returned.

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Effect of Fragment Removal on Development of Human Fragmented Embryos in IVF-ET Program (IVF-ET 시술 시 파편제거가 파편화된 인간배아의 발달에 미치는 효과)

  • Chi, Hee-Jun;Koo, Jung-Jin;Lee, Ju-Ok;Ryu, Hyoung-Eun;Kim, Kwang-Rae;Park, Chan;Roh, Sung-Il
    • Clinical and Experimental Reproductive Medicine
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    • v.37 no.4
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    • pp.339-348
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    • 2010
  • Objective: To investigate the beneficial effect of fragment removal on the subsequent cell division and clinical outcome of the fragmented human embryos. Methods: A prospective study was performed in Hanna Women's Clinic and Mizmedi Hospital. Sixty couples undergoing In vitro fertilization-embryo transfer (IVF-ET) program were participated in the present study. The microsurgical fragment removal was performed in 106 fragmented embryos of 29 patients before the transfer. As a control group, 122 fragmented embryos of 31 patients were transferred without the fragment removal. Effects of fragment removal on morphological changes and clinical outcomes of fragmented embryos were investigated. Results: Mean morphological grade (G2.79) of fragmented embryos was significantly improved after the fragment removal(G1.63, p<0.001). Most of the fragmented embryos did not show a regeneration of fragments after the fragment removal during the subsequent development, and a beneficial effect of fragment removal on the development of the fragment removed embryos was observed. Implantation and pregnancy rates of fragment removed embryos were 12.3% and 31.3%, whereas the rates of control group embryos were 6.6% and 22.5%, respectively. There was no statistical significance in the rates between the two groups because of the low number of trials. Conclusion: Microsurgical fragment removal improved the subsequent development as well as the morphological grade of fragmented embryos. The fragment removal may be beneficial for neighboring blastomeres by repairing the intercellular communication and removing the secretion of the potential toxic materials by fragments.

Effect on Survival and Developmental Competence of Vitrified Mouse Embryos Using Various Cryoprotectants and Cooling Speeds (생쥐 배아의 유리화 동결에 동결액의 조성과 냉각속도의 영향)

  • Park, Jae-Kyun;Go, Young-Eun;Eum, Jin-Hee;Won, Hyung-Jae;Lee, Woo-Sik;Yoon, Tae-Ki;Lee, Dong-Ryul
    • Clinical and Experimental Reproductive Medicine
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    • v.37 no.4
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    • pp.307-319
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    • 2010
  • Objective: Vitrification requires a high concentration of cyroprotectant (CPA) and an elevated cooling speed to avoid ice crystal formation. We have evaluated the effect of different combinations of cooling rate and CPA on embryonic integrity (developmental competence) in order to increase the efficiency of vitrification without impairing embryo viabilit. We hypothesized that the combination of CPA or the increase of cooling rates can reduce the concentration of toxic CPA for vitrification. As consequently, we performed experiments to evaluate the effect of various composition of CPA or slush nitrogen ($SN_2$) on the mouse embryonic development following vitrification using low CPA concentration. Methods: Vitrification of mouse embryos was performed with EM grid using liquid nitrogen ($LN_2$) or $SN_2$ and different composition of CPAs, ethylene glycol (EG) and dimethylsulfoxide (DMSO). After vitrification-warming process, their survival and blastocyst formation rates were examined. For analyzing long-term effect, these blastocysts were transferred into the uterus of foster mothers. Results: Survival and blastocyst formation rates of vitrified embryos were higher in EG+DMSO group than those in EG only. Furthermor, the group using $SN_2$ with a lower CPA concentration showed a higher survival of embryos and developmental rates than group using $LN_2$. Conclusion: The combination of EG and DMSO as CPAs may enhance the survival of mouse embryos and further embryonic development after vitrification. $SN_2$ can generate high survival and developmental rate of vitrified/warmed mouse embryos when a lower concentration of CPA was applied. Therefore, these systems may contribute in the improvement of cryopreservation for fertility preservation.

Marine Ecotoxicological Evaluation on HNS Spill Accident : Nitric Acid Spill Case Study (HNS 유출사고가 해양생물에 미치는 생물독성 영향평가 : HNO3 유출사고 대상)

  • Kim, Tae-Won;Kim, Young Ryun;Jo, So Eun;Son, Min Ho;Lee, Moonjin;Oh, Sangwoo
    • Journal of the Korean Society of Marine Environment & Safety
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    • v.21 no.6
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    • pp.655-661
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    • 2015
  • This study intends to evaluate the effect of nitric acid($HNO_3$) spill accidents on the marine ecosystem, while $HNO_3$ is known as one of the typical HNS. For this purpose, we performed (1) the growth inhibition test by using phytoplankton(Skeletonema costatum), (2) acute and chronic toxicity test by using invertebrate(Brachionus plicatilis and Monocorphium acherusicum), (3) fish(Cyprinodon variegatus) and (4) bacteria(Vibrio fischeri). In these tests, we observed the (1) pH changes induced by the nitric acid spill and (2) changes in nitrate($NO_3$) concentration disassociated from nitric acid after the accident, respectively. The toxicity test result on pH changes induced by $HNO_3$ shows that the no observed effect concentration(NOEC), lowest observed effect concentration(LOEC) and 50 % effect concentration($72h-EC_{50}$) values of M. acherusicum are pH 7 (0.3 mM), pH 5(1.1 mM) and pH 5.2(1.4 mM), respectively, indicating that M. acherusicum is the most sensitive species. The chronic toxicity test (population growth rate test) on $NO_3{^-}$ of B. plicatilis show that the NOEC, LOEC and $96h-EC_{50}$ are 5.9 mM, 11.8 mM and 32.6 mM, respectively, indicating that B. plicatilis is the most sensitive species. In conclusion, toxic effecst on the marine organism caused by the nitric acid spill accident is determined to be so slightly except for the most adjacent area of the ship in pH scale and such concentration of nitrate, to the extent of directly influencing the survival and reproduction of the marine organism, is determined practically not to be applicable in the typical accidents in the sea.

Disinfection of Fusarium-infected Rice Seeds by Prochloraz and Gaseous Chlorine Dioxide

  • Jeon, Young-ah;Lee, Young-yi;Lee, Ho-sun;Sung, Jung-sook;Lee, Seokyoung
    • 한국균학회소식:학술대회논문집
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    • 2014.10a
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    • pp.25-25
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    • 2014
  • Three species of Fusarium, F. fujikuroi, F. verticillioides and F. proliferatum, are known to be associated with bakanae disease of rice [1, 2]. F. fujikuroi infects rice flowers and survive in endosperm and embryo of the seeds. Infected seed is an important source of primary inoculum of pathogens [3]. Seeds of rice (Oryza sativa cv. Boramchan) collected from bakanae-infected field were found to be 96% infected with Fusarium sp., 52% with F. fujikuroi, 42% with F. verticillioides, and 12% with F. proliferatum as determined by incubation method and species-specific PCR assays. F. fujikuroi was detected at lemma/palea, endosperm and embryo whereas F. verticillioides and F. proliferatum were recovered only from lemma/palea by means of component plating test. Seed disinfection methods have been developed to control bakanae disease and prochloraz has been most widely used for rice seeds. Two chemicals formulated with prochloraz (PC 1) and prochloraz + hexaconazole (PC 2) that inhibit biosynthesis of ergosterol strongly reduced the incidence of Fusarium spp. on selective media to 4.7% and 2.0%, respectively. Disease symptoms of rice seedlings in nursery soil were alleviated by chemical treatment; seedlings with elongated leaves or wide angle between leaf and stem were strikingly reduced from 15.6 to 3.2% (PC 1) and 0 (PC 2), stem rots were reduced from 56.9 to 26.2% (PC 1) and 32.1% (PC 2), and normal seedling increased from 0.4 to 13.3% (PC 2). Prochloraz has some disadvantages and risks such as the occurrence of tolerant pathogens [4] and effects on the sterol synthesis in animals and humans [5]. For these reasons, it is necessary to develop new disinfection method that do not induce fungal tolerance and are safe to humans and animals. Chlorine dioxide ($ClO_2$), that is less toxic, produces no harmful byproducts, and has high oxidizing power, has been reported to be effective at disinfection of several phytopathogenic fungi including Colletotrichum spp. and Alternaria spp. [6]. Gaseous $ClO_2$ applied to rice seeds at a concentration of 20 ppm strongly suppressed mycelial growth of Fusarium fujikuroi, F. verticillioides and F. proliferatum. The incidence of Fusarium spp. in dry seed with 8.7% seed moisture content (SMC) tended to decrease as the concentration of $ClO_2$ increased from 20 to 40 ppm. Applying 40 ppm $ClO_2$ at 90% relative humidity, incidence was reduced to 5.3% and resulted in significant reduction of disease symptoms on MS media. In nursery soil, stem rot was reduced from 56.9 to 15.4% and the number of normal seedlings increased from 0.4 to 25.5%. With water-soaked seeds (33.1% SMC) holding moisture in the endosperm and embryo, the effectiveness of disinfection using $ClO_2$ increased, even when treated with only 20 ppm for four hours. This suggests that moisture was a key element for action of $ClO_2$. Removal of the palea and lemma from seeds significantly decreased the incidence of Fusarium spp. to 3.0%. Seed germination appeared to decrease slightly by water-soaking at $30^{\circ}C$ because of increased SMC and by physical damage of embryos from hulling. These results indicate that the use of gaseous $ClO_2$ was effective as a means to disinfect rice seeds infected with Fusarium spp. and that moisture around the pathogens in the seed was an important factor for the action of $ClO_2$. Further investigations should be conducted to ascertain the best conditions for complete disinfection of Fusarium spp. that infect deep site of rice seeds.

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Toxicity of lectin extracted from Korean mistletoe (Viscum album coloratum) in piglets and its effects on the immunogenicity of Aujeszky's disease virus vaccines (한국산 겨우살이(Viscum album coloratum)로부터 추출된 lectin의 돼지에 대한 독성 및 오제스키병 백신의 면역원성에 미치는 영향)

  • Yeo, Sang-Geon
    • Korean Journal of Veterinary Research
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    • v.46 no.3
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    • pp.225-234
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    • 2006
  • In the present study toxicity and immunostimulating activity of the lectin(KML-C), which was extracted from Korean mistletoe(Viscum album coloratum) were investigated in swine. To determine the toxicity, lectin was injected into thigh or cervical muscles of 4-week-old piglets(Landrace) and observed clinically and pathologically. For determination of the immnunostimulating activity, lectin($0.7{\mu}g/kg$ of body weight)-adjuvanted vaccine of Aujeszky's disease virus(ADV)(NYJ1-87) which was inactivated by 0.2% formalin was injected into the cervical muscle of antibody-negative piglets in the same age group. Subpopulation of the immune cells and serum neutralizing(SN) antibodies in the piglets were examined after vaccination, and resistance of the piglets against challenge by virulent NYJ1-87 was further examined. The results were also compared with those from piglets injected with aluminum hydroxide [$Al(OH)_3$]-adjuvanted vaccine of inactivated NYJ1-87 and NYJ1-87 vaccine without adjuvant, and the results are as follows. By injection of lectin with $30{\mu}g/kg$ of body weight to the thigh muscle, all of 12 piglets died after signs such as dyspnea, fever, systemic erythema and subcutaneous hemorrhages, and lesions pertaining to poisonous hepatitis and dysfunction of kidney were observed. By injection of lectin with $7{\mu}g/kg$ of body weight to the thigh muscle, all of 12 piglets showed signs such as edema and cutaneous hemorrhage in the injected area, lameness and depression, and lesions pertaining to poisonous hepatitis and dysfunction of kidney were observed. By injection of lectin with 1, 3 and $5{\mu}g/kg$ of body weight to the thigh muscle of each one piglet, signs such as congestion, induration and grayish coloration in the injected area, depression and inappetence were observed in all piglets. Toxic changes were also observed in the liver and kidney of piglets by lectin of 3 and $5{\mu}g$. By injection of lectin with 0.5 and $0.7{\mu}g/kg$ of body weight to the cervical muscle of each 9 piglets, all piglets were clinically normal and there were no significant changes in blood counts and chemistry values. Whereas, epithelial swelling and vacuolation of convoluted tubules were observed from one piglet injected with lectin of $0.7{\mu}g$, and necrosis and fibrosis of muscular fiber were observed in the muscle of one piglet injected with lectin of $0.5{\mu}g$. Only population of sIgM+ B lymphocytes increased among immune cells in all of 15 piglets immunized with lectin($0.7{\mu}g/kg$ of body weight)-adjuvanted vaccine, while compared to those in $Al(OH)_3$-adjuvanted vaccine and vaccine without adjuvant. No additional stimulation to the immune cells was recognized when lectin was added to $Al(OH)_3$-adjuvanted vaccine. In piglets immunized with lectin-adjuvanted vaccine, SN titers in reciprocal values for loge were 1.3-4.0 at 1-4 weeks after vaccination, which was similar to those with 1.0-3.3 by vaccine without adjuvant but lower than those with 2.0-5.7 by $Al(OH)_3$-adjuvanted vaccine. Also, no additional increase in the SN titers was recognized when lectin was added to $Al(OH)_3$-adjuvanted vaccine. Piglets immunized with lectin-adjuvanted vaccine were resistant to challenge by the virulent NYJ1-87 at 4 weeks after vaccination, and the SN titers reached to 5.0 one week after challenge, which was higher than those with 4.0 by vaccine without adjuvant but somewhat lower than those with 7.7 by $Al(OH)_3$-adjuvanted vaccine.

Hepatoprotective and Anticancer Activities of Allomyrina dichotoma Larvae (장수풍뎅이 유충의 간보호 효능 및 항암활성)

  • Lee, Ji-Eun;Jo, Da-Eun;Lee, An-Jung;Park, Hye-Kyung;Youn, Kumju;Yun, Eun-Young;Hwang, Jae-Sam;Jun, Mira;Kang, Byoung Heon
    • Journal of Life Science
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    • v.25 no.3
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    • pp.307-316
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    • 2015
  • Beetle larvae have been used as a traditional medicine to treat various human liver diseases. To prove the liver protective function of Allomyrina dichotoma larvae (ADL), we induced liver damage by the intraperitoneal injection of a hepatotoxic reagent, diethylnitrosamine (DEN), to C3H/HeN male mice and orally administered freeze-dried ADL powder. ADL powder lessened DEN-induced hepatotoxicity considering the reduced signs of acute and chronic hepatotoxicities, such as the ALP level in the blood serum, TUNEL-positive hepatocytes, ductural reactions, steatotic hepatocytes, and collagen deposition of the Masson’s trichrome staining. In addition to hepatoprotection, the anti-cancer activity of ADL has been examined. The ADL powder was extracted with ethanol and then fractionated with hexane, ethyl acetate, and water by a solvent partition technique. The ethyl acetate fraction showed cytotoxicity to various cancer cells through induction of apoptosis and necrosis, as well as the perturbed metabolism of the cancer cell to trigger autophagy. Collectively, ADL contains bioactive substances that can protect hepatocytes from toxic chemicals and trigger cell death in cancer cells. Thus, further purification and analyses of ADL fractions could lead to the identification of novel bioactive compounds.

Single Dose Oral Toxicity Test of Ethanol Extracts of Schisandrae fructus and Mori folium, and their Mixture in ICR Mice (ICR 마우스를 이용한 오미자, 상엽 에탄올 단독추출물 및 복합추출물의 단회경구투여 독성시험)

  • Choi, Eun Ok;Kwon, Da Hye;Kim, Min Young;Hwang-Bo, Hyun;Kim, Hong Jae;Ahn, Kyu Im;Jeong, Jin-Woo;Lee, Ki Won;Kim, Ki Young;Kim, Sung Goo;Choi, Young Whan;Hong, Su Hyun;Park, Cheol;Choi, Yung Hyun
    • Journal of Life Science
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    • v.26 no.10
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    • pp.1207-1213
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    • 2016
  • Schisandrae fructus (SF) and Mori folium (MF) have been used as traditional medicines for thousands of years in parts of Asia, including Korea, China, and Japan. Recent researches on SF and MF have documented a wide spectrum of therapeutic properties, including anti-microbial, anti-inflammatory, anti-oxidative, immunomodulatory and anti-angiogenesis effects. However, the toxicity and safety of SF and MF, and their mixture (medicinal herber mixture, MHMIX) were not confirmed. Therefore, this study was performed to evaluate the acute toxicity and safety of SF, MF and MHMIX. SF, MF and MHMIX were orally administered at a dose of 5,000 mg/kg in ICR mice. Animals were monitored for the mortality and changes in the body weight, clinical signs and gross observation during the 14 days after dosing, upon necropsy. We also measured parameters of organ weight, clinical chemistry, and hematology. No dead and no clinical signs were found during the experiment period after administration of a single oral dose of SF, MF and MHMIX. There were no adverse effects on clinical signs, body weight, or organ weight and no gross pathological findings in any treatment group. Therefore, LD50 value of SF, MF and MHMIX may be over 5,000 mg/kg and it may have no side toxic effect to ICR mice. The results on the single-dose toxicity of SF, MF and MHMIX indicate that it is not possible to reach oral dose levels related to death or dose levels with any harmful side effects.

A Study on the Legislative Conception of Terror of the Advanced European Nations (유럽 선진국의 법제적 테러 개념에 관한 고찰)

  • Kwon, Jeong-Hun;Kim, Tae-Hwan
    • Korean Security Journal
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    • no.15
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    • pp.29-50
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    • 2008
  • Many countries throughout the world have enacted laws on terrorism in the light of the changes that time has brought to them, geographical features, cultural values, and environmental elements. Especially some advanced European nations prescribe the definition of terrorism, the purpose of terrorism, the behavior of terrorism, and the types of crimes related to terrorism and so on for the following reason that it is more vital for the authorities concerned to investigate and punish terrorists after the rise of terrorism. In this regard, this paper analyzes legislative countermoves against terrorists of advanced countries such as France, Germany, and England and through this sheds light on the need of future anti-terrorism bills. The legislative basic guidelines directly to manipulate future terrors based on theories derived from this study could be summarized as follows. In the first place, providing laws on direct investigative power and harsher punishment to those involved in terrorism is a prerequisite for social security and thus the presidential directive of the state anti-terrorism action guidelines just deals with administrative measures without any effective response to terrorism. Hence it is urgent to make anti-terrorism bill concerning investigation and punishment of terrorists. In the second place, it is associated with the objectives of terror. The expression "all sorts of" stated in Korean law is so quite unclear that it can not fulfill the required conditions for naming it "crime". Comprehending provisoes of the crime that meets the purpose of the terrorists is necessary in order to investigate and inflict punishment on them. Therefore, it is advisable to establish specific and precise principles such as political, social, ideological, and religious purpose of terrorists in the bill. In the third place, to meet the flow of times of technicalization, informatization, such provisoes as destruction of electronic data system, crimes related to nuclear materials, purchases of weapons by terrorists, tax administration for prohibition of sale, and arson should be considered in terror bill. In the fourth place, nonselective attack toward unspecified individuals has become a serious issue in our society. Terrorists leave poisonous foods or beverages to crowded place or dump toxic chemicals into river intentionally. Therefore more strict regulations must be included in terror bill to prevent possible terrorist attacks.

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