• The Journal of the Korean Society for Microbiology
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• v.20 no.1
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• pp.115-125
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• 1985

Hemorrhagic fever with renal syndrome (HFRS) is a debilitating disease of humans caused by Hantaan virus (HV), the prototype member of a newly proposed genus of Bunyaviridae. Studies of HV pathogenesis have been limited by the absence of a well defined model for a virus-induced disease state. In an attempt to devise a model for HV pathogenesis in laboratory rodents, newborn outbred suckling ICR mice were shown to be uniformly susceptible to lethal infection with non- mouse adapted HV by intracerebral (IC), intraperitoneal (IP), intramuscular (IM), and subcutaneous (SC) inoculation routes. Clinical coures, mean time to death, and fatal outcome were age-dependent. With an inoculum of 10 $LD_{50}$, mortality was 100% in mice infected within 72h of birth, but declined to 50% by 7 days. By 2-2.5 weeks, animals developed complete resistance to clinical disease. Virus was consistently detected in serum by day 6 post-infection in IC- and IP- inoculated animals, and reached peak levels of $10^5\;PFU/ml$ by day 8 Mice infected IM and SC showed delays in onset of viremia, but achieved similar titers. Immunofluorescent antibody appeared by 17-18 days, and neutralizing antibody by 15 days, in all experimental groups. Two of 8 inbred mouse strains were identified as resistant to clinical disease : SJL/J and A/J. Manipulation of this model will allow investigation of natural rodent pathogenesis with HV, as well as offer insight into disease mechanisms and therapy of HFRS.

• Toxicological Research
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• v.13 no.1_2
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• pp.61-69
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• 1997

Exposure of splenocytes to 2-chloroethylethyl sulfide (CEES) resulted in the cell death, and the cytotoxicity of CEES was prevented by inhibitors of lysosomal hydrolases. Therefore, it has been postulated that the cytotoxicity of CEES may be partially due to the lysosomal labilization. This study, based on this mechanism, was undertaken to determine whether aminoglycoside antibiotics as inhibitors of lysosomal phospholipases and their combinations with other lysosome stabilizers can be useful as a treatment to reduce the CEES toxicity in mice. 2-Chloroethylethyl sulfide (20 mg/kg body weight) was injected ip into female ICR mice, and candidate compounds were administered ip before or after the CEES challenge. Kanamycin (40 mg/kg body weight) as effective as deferoxamine (100 mg/kg body weight) enhanced the survival rate after 5 days of intoxication from 10% of control to 50 - 60%. The most effective was found to be the combination of kanamycin, cycloheximide, deferoxamine and dextrose showing an almost full protection against 2LD50 of CEES. Consistent with the protection of the CEES toxicity, the decrease of body weight in mice intoxicated with CEES was effectively prevented by kanamycin or its combinations. It is suggested that kanamycin or its combination (kanamycin, cycloheximide, deferoxamine and dextrose) would be one of effective antidotes against the CEES poisoning in mice.

• Environmental Analysis Health and Toxicology
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• v.18 no.2
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• pp.137-143
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• 2003

To validate and to estimate the chemical hazard playa very important role to environment and human health. The detection of many synthetic chemicals used in industry that may pose a genetic hazard in our environment is of great concern at present. Since these substances are not limited to the original products, and enter the environment, they have become widespread environmental pollutants, thus leading to a variety of chemicals that possibly threaten the public health. In this resepct, the clastogenicity of 8 synthetic chemicals was evaluated with bone marrow micronucleus assay in mice. The positive control, mitomycin C(2mg/kg,i.p.) revealed significant induction ratio of percentage of micronucleated polychromatic erythrocytes/l,000 polychromatic erythrocytes compared to carboxymethylcellulose control. The chemicals with relatively high LD$\_$50/ value such as phenylisocyanate (CAS No. 103-71-9), m-aminochlorobenzene (CAS No. 108-42-9) and 2-chloro-4-nitroaniline (CAS No. 121-87-9) revealed no significant induction of micronucleated polychromatic erythrocytes in mice. From this results, 8 synthetic chemicals widely used in industry have revealed no significant micronucleus induction of clastogenicity in mice in this experiment.

• Korean Journal of Optics and Photonics
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• v.10 no.1
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• pp.73-79
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• 1999

Semiconductor optical switch modules of 1$\times$2, 1$\times$4, and 4$\times$4 types for 1550 nm optical communication systems were fabricated by using laser welding technique, embodying in 30-pin butterfly package. For better coupling efficiency between switch chip and optical fiber, tapered fibers of 10~15mm lens radii were used, which provided up to 60% optical coupling efficiency. With the help of new laser hammering process, we could recover the lost optical power almost completely up to average 82% of initially obtained power. The fabricated optical switch modules showed good thermal stability of less than 5% degradation even after 200 times thermal cycling test. The 2.5 Gbps optical transmission characteristics of the 4$\times$4 switch module showed low sensitivities of less than -30dB for all possible switching paths. The transmission penalties of 1$\times$2 switch module at $10^{-10}$ BER were 0.6dB and 0.7dB for 50Xm and 90 Km optical fibers, respectively.

• Toxicological Research
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• v.14 no.3
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• pp.427-433
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• 1998

The acute and genetic toxicity of DK1002 was subjected in this study. DK1002 which is a morphine-like new drug candidate synthesized by Dong-Kook Pharmaceutical Co. Ltd. is now under developing as a analgesics that have better drug efficacy and least addictive property. In acute toxicity study, the 50% lethal doses ($LD_{50}$) of DK1002 were determined as>2000mg/kg (p.o.), 237.0mg/kg(i.p.), 57.5mg/kg(i.v.), and 1266.9mg/kg (s.c.). And also, to study the genotoxicity of DK1002, we performed bacterial reversion assay with Salmonella typhimurium TA98, TA100, TA1535, and TA1537, and in vitro chromosomal aberration assay with Chinese hamster lung cells in the presence and absence of S-9 metabolic activation system. In vivo micronucleus assay using mouse bone marrow cells was also performed. From these results, DK1002 was revealed nonmutagenic potential in S. typhimurium TA98, TA100, TA1535, and TA537 both in the absence and presecne of metablic activation system. No clastogenicity of DK1002 was observed in chromosomal aberration assay in vitro as well as in micronucleus assay in vivo.

• Toxicological Research
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• v.34 no.1
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• pp.55-63
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• 2018

As a part of general toxicity studies of Enterococcus Faecalis 2001 (EF 2001) prepared using heat-treatment bacillus mort body EF 2001 in mice, this study examined the toxicity of EF 2001 in single and repeated administrations following the previous report in order to apply this product to preventive medicine. The safety of oral ingestion of EF 2001 was examined in 6-week-old male and female ICR mice with 1,000 mg/kg, 3,000 mg/kg and 5,000 mg/kg body weight/day administrated by gavage of the maximum acceptable dose of EF 2001. The study was conducted using distilled water as a control following the methods for general toxicity studies described in the "Guidelines for Non-clinical Studies of Pharmaceutical Products 2002". As a control, 1) observation of general conditions, 2) measurement of body weight, 3) determination of food consumption, 4) determination of water consumption, 5) blood test and urinalysis and 6) pathological examination were performed for the administration of EF 2001. Mice received EF 2001 for 13 weeks and results were compared with those of the control group that received distilled water. The results of the above examinations revealed no significant differences between control and EF 2001 groups for both males and females. Thus, no notable toxicity was confirmed with single and repeated oral administrations of EF 2001. Oral administration in the above doses did not result in abnormal symptoms or death during the observation period. No abnormalities in blood cell count or organ weights were seen. Without any evidence of toxicity to cells and organs, EF 2001 is speculated to not adversely affect living organisms. The 50% lethal dose of EF 2001 with oral administration in mice is estimated to be greater than 5,000 mg/kg body weight/day for both male and female mice. Therefore, $LD_{50}$ value for animals was 5,000 mg/kg or more.

• BMB Reports
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• v.38 no.1
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• pp.41-48
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• 2005

In this study we developed the transposon-mediated shuttle vector 'Hanpvid', which composed of HaNPV (Heliothis armigera nuclear polyhedrosis virus) genomic DNA and a transposon cassette from Bacmid of Bac-to-Bac system. Hanpvid replicates in E. coli in the same way as Bacmid and retains infective function in cotton bollworm cells (Hz-AM1). Using Hanpvid we constructed a recombinant virus, which could infect Hz-AM1 cells and generate recombinant HaNPV (rHa-Bar) containing the barnase gene, a ribonuclease gene from Bacillus amyloliquefaciens. Since the expression vector carrying barnase gene cannot replicate in the absence of barstar, a specific inhibitor of barnase, we constructed a new cotton bollworm cell line (AM1-NB) using the marker rescue method. In AM1-NB barstar was integrated into the cellular chromosome to sustain the replication of rHa-Bar. To screen out recombinant HaNPV for potential use as biopesticide, Hz-AM1 and AM1-NB cell lines were infected with rHa-Bar, respectively. The results obtained indicate that Viral progenies in AM1-NB were 23 and 160 times greater than those in Hz-AM1 48 h and 72 h after infection, respectively. With additional insertion of the polyhedron gene from AcNPV (Autographa californica nuclear polyhedrosis virus) into the Hanpvid genome, rHa-Bar regained the polyhedron phenotype and its pest-killing rate greatly improved. Toxic analysis showed that the lethal dosages ($LD_{50}$) and the lethal time(s) ($LT_{50}$) of rHa-Bar were reduced by 20% and 30%, respectively, compared to wt-HaNPV in the third instar larvae of cotton bollworm. This study shows that in AM1-NB barnase can be effectively produced and used as pest-killing agent for the biological control of cotton pests.

• The Journal of Internal Korean Medicine
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• v.33 no.1
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• pp.62-68
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• 2012

Objectives : This study aimed to evaluate the single oral dose toxicity of Seonpyejeongcheon-tang (SJT) in male and female Sprague-Dawley rats. Methods : In this single oral toxicity study, rats were orally administrated in a single dose of 0 or 5,000 mg/kg SJT. There were 7 rats in each group. After single administration, mortality, clinical signs, body weight changes and gross pathological findings were observed for 14 days. Organ weight, clinical chemistry and hematology were tested after 14 days. Results : There was no mortality or other clinical signs for 14 days. There were also no significant differences in body weight, organ weights, hematological and serum chemical parameters between the SJT and control groups. Conclusions : The results obtained in this study suggest that the 50% lethal dose of SJT is over 5,000 mg/kg, so this finding can be expected to provide scientific evidence for the safety of SJT.

• Toxicological Research
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• v.17
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• pp.109-115
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• 2001

Abrus agglutinin was purified from the kernels of Abrus precatorius by Sepharose 4B affinity column chromatography followed by Sephadex G-100 gel filtration column chromatography. About 1.25 g of abrus agglutinin was obtained from 1 kg of the kernels. The LD$_{50}$ of abrus agglutinin is 5 mg/kg of body weight, which is less toxic than that of abrin, 20$\mu\textrm{g}$/kg body weight. The amino acid sequence of abrus agglutinin was determined by protein sequencing techniques and deduced from the nucleotide sequence of a cDNA clone encoding full length of abrus agglutinin. There are 258 residues, 2 residues and 267 residues in the A-chain, the linker peptide and the B-chain of abrus agglutinin, respectively. Abrus agglutinin had high homology to abrin-a (77.8%). The 13 amino acid residues involved in catalytic function, which are highly conserved among abrin and ricin, were also conserved within abrus agglutinin. The protein synthesis inhibitory activity of abrus agglutinin ($IC_{50}$/ = 3.5 nM) was weaker than that of abrin-a (0.05 nM). By molecular modeling followed by site-directed mutagenesis showed that Pro199 of abrus agglutinin A-chain located in amphipathic helix H and corresponding to Asn200 of abrin A-chain, can induce bending of helix H. This bending would presumably affect the binding of abrus agglutinin A-chain to its target sequence GpApGpAp, in the tetraloop structure of 285 r-RNA subunit and this could be one of major factors contributing to the relatively weak protein synthesis inhibitory activity and toxicity of abrus agglutinin.n.

• Journal of Acupuncture Research
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• v.37 no.2
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• pp.110-117
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• 2020

Background: The aim of this pilot study was to assess the safety and dosing of scolopendrid pharmacopuncture (SPP). Methods: A total of 40 healthy Sprague-Dawley rats (males and 20 females 20) were selected following a 7-day inspection and acclimation period. SPP was administered via intramuscular injection, over a 2-week period using 3 doses including a high-dose [0.84 mg of scolopendrid per kg of body weight (BW)], a med-dose (0.42 mg/kg BW), and a low-dose (0.21 mg/kg BW). The control group was injected with sterile water into the muscles. Unusual changes caused by administration of the test substance were observed. Weight, feed intake, organ weight, and hematological examinations were compared among the groups. Using the SPSS statistical program, Levene's test was performed to evaluate the homogeneity of variances, and a one-way ANOVA test was subsequently performed to assess the significance between each test group. Results: During the experiment no animals died. Weight change, food consumption, organ weight, hematological test, and blood biochemical tests showed no significant differences in the treatment groups compared to controls. Conclusion: No toxicological changes related to the administration of test substances were observed. Therefore, the LD₅₀ (lethal-dose that kills 50%) of scolopendrid pharmacoupuncture in rats was greater than 0.84 mg/kg.