• Molecular & Cellular Toxicology
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• v.5 no.1
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• pp.32-43
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• 2009

Acetaminophen (APAP) overdose is known to cause severe hepatotoxicity mainly through the depletion of glutathione. In this study, we compared the cytotoxic effects of APAP on both a normal murine hepatic cell line, BNL CL.2, and its SV40-transformed cell line, BNL SV A.8. Gene expression profiles for APAP-treated cells were also obtained using microarray and analyzed to identify differences in genes or profiles that may explain the differences of susceptibility to APAP in these cell lines. These two cell lines exhibited different susceptibilities to APAP (0-$5,000{\mu}M$); BNL SV A.8 cells were more susceptible to APAP treatment compared to BNL CL.2 cells. A dose of $625{\mu}M$ APAP, which produced significant differences in cytotoxicity in these cell lines, was tested. Microarray analysis was performed to identify significant differentially expressed genes (DEGs) irrespective of APAP treatment. Genes up-regulated in BNL SV A.8 cells were associated with immune response, defense response, and apoptosis, while down-regulated genes were associated with catalytic activity, cell adhesion and the cytochrome P450 family. Consistent with the cytotoxicity data, no significant DEGs were found in BNL CL.2 cells after treatment with $625{\mu}M$ APAP, while cell cycle arrest and apoptosis-related genes were up-regulated in BNL SV A.8 cells. Based on the significant fold-changes in their expression, a genes were selected and their expressions were confirmed by quantitative real-time RT-PCR; there was a high correlation between them. These results suggest that gene expression profiles may provide a useful method for evaluating drug sensitivity of cell lines and eliciting the underlying molecular mechanism. We further compared the genes identified from our current in vitro studies to the genes previously identified in our lab as regulated by APAP in both C57BL/6 and ICR mice in vivo. We found that a few genes are regulated in a similar pattern both in vivo and in vitro. These genes might be useful to develop as in vitro biomarkers for predicting in vivo hepatotoxicity. Based on our results, we suggest that gene expression profiles may provide useful information for elucidating the underlying molecular mechanisms of drug susceptibility and for evaluating drug sensitivity in vitro for extrapolation to in vivo.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.12 no.11
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• pp.5012-5018
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• 2011

According to the nationwide survey of tuberculosis from 1965 to 1995, the incidence and drug resistance rate of tuberculosis have been decreased in Korea, but the prevalence of multidrug resistance of Mycobacterium tuberculosis is still a serious problem. The purpose of this study is to investigate the drug resistance rate and pattern of tuberculosis in Daejeon from 2001 to 2008. Of the total 581cases where the drug susceptibility test was performed, resistance to at least one anti-TB drug was found in 104 cases(17.9%) of these, 68(11.7%) were resistant to at least INH and 41(7.1%) were resistant to at least RFP. Single-drug resistance was found for isolates from 37(6.4%) ; 18(3.1%) of these were resistant to INH and 5(0.9%) to RFP. Multidrug resistance, where TB was resistant to at least isoniazid and refampin, was found in 35 cases(6.0%). and Factors associated with MDR-TB included age under 40-60.The drug-resistance rate of pulmonary TB, especially MDR-TB, is higher in the initial treated patients at a private referral hospital than in those in the pubulic sector. Initial drug resistance is common and the drug susceptibility test is informative for pulmonary TB patients who have not received previous TB treatment. The need for an improved control program, coupled with early diagnosis of MDR-TB, to reduce the spread and development of resistance. Multidrug resistance rate is still problem in korea. Efforts to decrease multidrug resistance rate either independently or in cooperation with the pubulic sector will be needed.

• Biomolecules & Therapeutics
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• v.29 no.2
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• pp.234-247
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• 2021

We used a heterozygous gene deletion library of fission yeasts comprising all essential and non-essential genes for a microarray screening of target genes of the antifungal terbinafine, which inhibits ergosterol synthesis via the Erg1 enzyme. We identified 14 heterozygous strains corresponding to 10 non-essential [7 ribosomal-protein (RP) coding genes, spt7, spt20, and elp2] and 4 essential genes (tif302, rpl2501, rpl31, and erg1). Expectedly, their erg1 mRNA and protein levels had decreased compared to the control strain SP286. When we studied the action mechanism of the non-essential target genes using cognate haploid deletion strains, knockout of SAGA-subunit genes caused a down-regulation in erg1 transcription compared to the control strain ED668. However, knockout of RP genes conferred no susceptibility to ergosterol-targeting antifungals. Surprisingly, the RP genes participated in the erg1 transcription as components of repressor complexes as observed in a comparison analysis of the experimental ratio of erg1 mRNA. To understand the action mechanism of the interaction between the drug and the novel essential target genes, we performed isobologram assays with terbinafine and econazole (or cycloheximide). Terbinafine susceptibility of the tif302 heterozygous strain was attributed to both decreased erg1 mRNA levels and inhibition of translation. Moreover, Tif302 was required for efficacy of both terbinafine and cycloheximide. Based on a molecular modeling analysis, terbinafine could directly bind to Tif302 in yeasts, suggesting Tif302 as a potential off-target of terbinafine. In conclusion, this genome-wide screening system can be harnessed for the identification and characterization of target genes under any condition of interest.

• Journal of Food Hygiene and Safety
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• v.21 no.1
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• pp.23-30
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• 2006

Antimicrobial susceptibility and multiple drug resistance patterns have been carried out on total of 364 isolates of Salmonella enterica serovar Enteritidis isolated from foodborne patients in Seoul from 2001 to 2005. Overall, the highest percentage of resistance was found to the following antimicrobial agents: streptomycin (46.7%), ampicillin (37.3%), ticarcillin (36.7%), tetracycline (36.0%), nalidixic acid (20.7%), chloramphenicol (13.3%), amoxicillin/clavulanic acid (6.7%) and Ampicillin/sulbactam (4.0%). Seventy five percentage of isolates were found to be resistant to one or more of the antimicrobes tested. The resistant rates to nalidixic acid and chloramphenicol in S. Enteritidis tested were annually increased but the resistant rate to tetracycline was decreased and the resistant rates to streptomycin, ampcilin and ticarcillin were remained steadily. The most frequent patterns of multiresistant isolates were only nalidixic acid resistant (18.0%) and streptomycin-tetracycline (18.0%), streptomycin-ampicillin-ticarcillin (10%), and ampicillin-ticarcillin (5.5%). Overall the resistant rates of 1 drug was 19.3%,2 drugs 24.7%, 3 drugs 6.7% and 4 or more drugs 24.0%. The resistant rates of 1 drug and 2 drugs in 2005 were increased dramatically.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.11a
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• pp.87-91
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• 1997

The range of disorders of old age that are thought potentially amenable to drug therapy is increasing. However, factors such as the growing costs of drug development and prescription, the novel pharmacological profile and enhanced potency of many new compounds, and the concerns that the elderly may have enhanced susceptibility to toxicity all make drug usage in the elderly patient an increasingly specialized topic. This is compounded by the high incidence of multiple disorders in frail elderly patients, and consequently the possibility of the long term use of several drugs, thus, adding the risk of drug interactions. Thus, clinical pharmacology in the elderly requires understanding of pharmacologic characteristic determinants of the physiological changes (Table 1) associated with aging in terms of pharmacokinetics and pharmacodynamics.

• Journal of Microbiology
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• v.45 no.1
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• pp.64-68
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• 2007

In this study we examined the multi-drug resistance profiles of the tetracycline (TC) resistant genus Vibrio to determine its susceptibility to two ${\beta}-lactams$, ampicillin (ABPC), and mecillinam (MPC), as well as to macrolide, erythromycin (EM). The results showed various patterns of resistance among strains that were isolated from very close geographical areas during the same year, suggesting diverse patterns of drug resistance in environmental bacteria from this area. In addition, the cross-resistance patterns suggested that the resistance determinants among Vibrio spp. are acquired differently within the sediment and seawater environments.

• Childhood Kidney Diseases
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• v.10 no.2
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• pp.192-200
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• 2006

Purpose : This study was performed to identify longitudinal changes in the prevalence of organisms isolated from urinary tract infection(UTI) and in the pattern of Escherichia coli susceptibility to antibiotics during the past 10 years in children with UTI. Methods : We performed a retrospective study of a total of 192 urine cultures from children with UTI in the Department of Pediatrics, Seoul Adventist Hospital over two periods(1st: 1995-2000, 2nd:2001-2005). Antimicrobial susceptibility of the isolates was compared between the two groups. Results : The pathogens of UTI in the two groups were similar. In the first period, E. coli was the leading uropathogen(66.2%) followed by Klebsiella pneumoniae(7.8%), Enterobacter cloacae(6.5%), and others(19.5%). In the second period, E. coli was the leading uropathogen(67%) followed by K. pneumoniae(12.2%), E. cloacae(3.5%), Enterobacter aerogenes(3.5%), and others(13.8%). The susceptibility pattern of E. coli to amoxicillin/clavulanate(87.5%, 81.0%) did not present any statistically significant difference between the two periods(P>0.05). The susceptibility of E. coli to TMP/SMX(52.4%, 50.0%) was still low with no significant difference between the two periods(P>0.05). Conclusion : Our results suggest that the use of amoxicillin/clavulanate is still an excellent therapeutic option in children with UTI. The low rate of susceptibility to TMP/SMX against uropathogens suggest that TMP/SMX may be reevaluated as the first-line therapeutic drug for UTI.

• Journal of Microbiology and Biotechnology
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• v.19 no.7
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• pp.734-741
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• 2009

Recently, strains of methicillin-resistant Staphylococcus aureus (MRSA) with reduced susceptibility to vancomycin (VCM) have been clinically isolated. The antibacterial activity of a new drug, linezolid (LZD), in such a strain was evaluated by measuring bacterial metabolic activity. A total of 73 MRSA strains having various susceptibilities to VCM were subjected to a novel and highly sensitive chemiluminescence-based assay. LZD MIC in the tested strains, measured by the microbroth dilution method, was within the range 1-4 mg/l (mostly ${\leq}2$mg/l), except for one LZD-resistant strain (NRS127; MIC=7 mg/l), and showed no correlation with VCM resistance. The chemiluminescence assay demonstrated that bacterial metabolic activity was strongly suppressed with increasing LZD concentration. The chemiluminescence intensity curve had a low baseline activity without tailing in most strains. The present results suggest that LZD has strong antibacterial activity against MRSA strains, and would be effective for treatment of infections that are poorly responsive to VCM. The chemiluminescence assay facilitated sensitive and discriminative susceptibility testing within a relatively short time.

• Korean Journal of Veterinary Research
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• v.50 no.3
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• pp.231-237
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• 2010

This study was conducted to investigate characteristics and antimicrobial susceptibility of Escherichia (E.) coli isolates isolated from vaginal mucosa and clitorial fossa of 105 Thoroughbred mares suspicious of the genital disease in Korea during the period from March 2006 to July 2007. Ninety six E. coli isolates were identified as standard biochemical properties and using BIOLOG system. Fifty three isolates (55.2%) could be classified into a total of 21 O serotypes and forty three isolates (44.8%) were non-typeable with 51 O antisera used in this study. The verotoxin 1 (VT 1) and verotoxin 2 genes were analyzed by multiplex PCR. Among them, one isolate was detected VT 1 gene (130 bp). Most of isolates showed a high susceptibility in ciprofloxacin (100%), enrofloxacin (100%), norfloxacin (100%), cefoxitin (96.9%), gentamicin (96.9%), sulphamethoxazole (96.9%), nitrofurantoin (94.8%), amikacin (93.8%), nalidixic acid (92.7%) and tetracycline (90.6%). These results may provide the basic information to establish strategies for the treatment and prevention of reproductive disease in Thoroughbred mares in Korea.

• Korean Journal of Veterinary Service
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• v.19 no.2
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• pp.115-125
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• 1996

A total of 315 microorgainisms were isolated from 256 pneumonic lung samples of pig in abattoirs of northern Chungnam area during February to November 1994, and Identified 97 strains as Pusteurella multocida, 89 strains as Staphylococcus spp, 54 strains as Streptococcus spp, 22 strains as Mycoplasma spp, 21 strains as Escherichia coli, 18 strains as Haemophilus parsuis, 11 strains as Corymebacteroi, pyogenes, and 3 strains as Acrinobacillus spp by Gram's and Dienes stain, and biological properties test Involved API system. After that, they were examined anti biotic susceptibility for ampicillin(AM), cephalothin(CF), chloramphenicol(CP), erythromycin(EM), kanamycin(KM), gentamicin(GM), neomycin(NM), penicillin(PC), streptomycin(SM), tetracycline(TE), tiamulin(TIA), tylosin(TYL), methicillin(DP), colistin(CL) and trimet hoprim(SXT). In antibiotics susceptibility test, 293 isolates except Mycoplasma spp 22 strain were highly susceptible to DF(79.2%) and AM(76.2%), but resistant to PC(14.0%), NM(19.5%) and KM (23.2%) The multiple drug resistant patterns were noted in most isolates, whereas only 7 isolates resistant to single drugs.