• Toxicological Research
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• v.24 no.1
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• pp.29-36
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• 2008

The present study investigated the anti-proliferative and chemosensitizing effects of Crinum asiaticum var. japonicum against multi-drug resistant (MDR) cancer cells. The 80% methanol extract, chloroform ($CHCl_3$) fraction and butanol (BuOH) fraction of C. asiaticum inhibited the growth of mitoxantrone (MX) resistant HL-60 (HL-60/MX2) cells. When HL-60/MX2 cells were treated with the $CHCl_3$ and BuOH fractions, DNA ladder and sub-G1 hypodiploid cells were observed. Furthermore, the fractions reduced BcI-2 mRNA levels, whereas Bax mRNA levels were increased. These results suggest that the inhibitory effect of C. asiaticum on the growth of the HL-60/MX2 cells might arise from the induction of apoptosis. Treatment of HL-60/MX2 cells with the fractions markedly decreased the mRNA levels of the multi-drug resistance protein-1 and breast cancer resistance protein. The $CHCl_3$ fraction and hexane fraction increased MX accumulation in HL-60/MX2 cells. These results imply that the $CHCl_3$ fraction of C. asiaticum plays a pivotal role as a chemosensitizer. We suggest that components of C. asiaticum might have a therapeutic potential for the treatment of MDR leukemia.

• Korean Journal of Veterinary Service
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• v.32 no.1
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• pp.49-59
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• 2009

At the present study, it was aimed to explore the states of antimicrobial resistant Salmonella spp. isolates from 3,850 pigs (2,732 ileocecocolic lymphnodes and 1,118 cecal contents) and 1,764 cattle (965 cecal lymphnodes and 799 cecal contents) slaughtered in Busan province from December 2000 to November 2001. Among 5,614 samples, 457 of Salmonella spp. were isolated from pig lymphnodes (13.5%), pig cecal contents (4.4%), cattle lymphnodes (3.5%) and cattle cecal contents (0.5%). Salmonella spp. were showed different isolation ratio, that was 10.8% in summer, 9.0% in autumn, 8.4% in spring and 5.0% in winter. As a result of serotyping, B group (65.4%) were identified as the most common in pigs and cattle, in order of $C_1$ (14.0%), $D_1$ (5.5%), $C_2$ (4.2%), $E_1$ (4.2%) and L (3.5%). 34 serotypes were found, among them, Salmonella Typhimurium (S. Typhimurium) (21.0%) was the most common serotype from pigs and cattle. The major serotypes were in order of S. Derby (15.3%), S. Schwarzengrund (14.7%), S. Typhimurium var Copenhagen (9.2%), S. Mbandaka (5.7%), S. Enteritidis (5.5%) and S. Ruiru (3.5%). The most common serotype was S. Typhimurium in pigs, and S. Ruiru in cattle. S. Ruiru was firstly isolated from pigs and cattle in Korea. In antimicrobial susceptibility test, all the isolates were demonstrated susceptibility to norfloxacin and ofloxacin. But the isolates were showed resistance other antibiotics in order of doxycycline (68.3%), tetracycline (67.8%), penicillin (54.5%) and streptomycin (52.5%). S. Typhimurium were exhibited resistance to ampicillin (34.8%), chloramphenicol (36.2%), streptomycin (94.9%), sulfamethoxazole/trimethoprim (34.8%) and tetracycline (97.8%). There were 53 strains (38.4%) which had multi drug resistant (MDR) isolates, resistant to more than 6 antimicrobial agents. The most common resistance patterns of MDR isolates were ampicillin, chloramphenicol, carbenicillin, doxycycline, nalidixic acid, penicillin, streptomycin, sulfamethoxazole/trimethoprim and tetracycline (ACCbDNaPSSuT).

• Korean Journal of Clinical Laboratory Science
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• v.51 no.4
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• pp.444-452
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• 2019

Carbapenem resistance, mediated by the major acquired metallo-β-lactamase (MBL) genes, has been increasingly reported, particularly for clinical isolates of Acinetobacter spp. Of the 191 nonduplicate clinical isolates of the carbapenem-nonsusceptible Acinetobacter spp. evaluated, 125 isolates (65.4%) were positive for the modified imipenem or meropenem-Hodge test, and 49 isolates (25.7%) were positive for the imipenem-EDTA+SMA double disk synergy test (DDS). PCR and sequencing of the bla_VIM-2-allele and bla_IMP-1-allele showed that 29 A. baumannii isolates and 1 A. calcoaceticus isolate had bla_VIM-2, whereas 16 A. baumannii isolates and 2 A. calcoaceticus isolates had bla_IMP-6; 1 isolate of the A. genomospecies 3 had bla_VIM-2 and bla_AIM-1. All the above MBL genes belong to class 1 integron. The size of class 1 integron encompassing bla_VIM-2 or bla_IMP-6 ranges from 2.8 kb to 3.2 kb in clinical isolates of A. baumannii, and 3.2 kb to 3.5 kb in clinical isolates of A. genomospecies 3. bla_VIM-2 was most often located first or second in the class 1 integron, and these integrons often included aacA4. Due to dispersion of the MBL-producing Acinetobacter spp. as well as integron, which may encompass various resistance genes, there is an expectation for the increase of multidrug resistant Gram-negative bacteria, including resistance of carbapenems such as imipenem or meropenem. Hence, the development of new antimicrobial agents for treating severe Acinetobacter spp. infections is needed.

• Microbiology and Biotechnology Letters
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• v.50 no.1
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• pp.89-94
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• 2022

Triclosan (TCS) is an antimicrobial agent used in various human personal care products against both gram-positive and gram-negative bacteria. The purpose of this study was to evaluate the presence of TCS-resistant bacteria in sewage water in Peshawar, Khyber Pakhtunkhwa (KPK), Pakistan, for the first time. TCS-supplemented Luria Bertani (LB) agar was used to isolate TCS-tolerant bacteria. A total of 17 TCS-resistant isolates were randomly selected from a large pool of bacteria that showed growth on TCS-supplemented LB agar. Based on gram staining and physiochemical characteristics, the isolated strains were identified as Salmonella typhi (n = 6), Escherichia coli (n = 4), Citrobacter freundii (n = 4), Proteus mirabilis (n = 1), Enterobacter cloacae (n = 1), and Pseudomonas aeruginosa (n = 1). The Triclosan mean minimum inhibitory concentrations (MICs) for the isolates of Salmonella typhi, Escherichia coli, Citrobacter freundii, Proteus mirabilis, Enterobacter cloacae, and Pseudomonas aeruginosa were 23.66 ㎍ ml^-1, 18.75 ㎍ ml^-1, 42 ㎍ ml^-1, 32 ㎍ ml^-1, 64 ㎍ ml^-1, and 128 ㎍ ml^-1, respectively. The antibiogram revealed that all isolates were resistant to penicillin G (100%) and linezolid (100%), followed by ampicillin (94%), tetracycline (76%), tazobactam (76%), sulbactam/cefoperazone (64%), polymyxin PB (58%), amikacin (29.41%), aztreonam (29.41%), imipenem (5%), and gentamicin (5%). This is the first known study regarding the isolation of TCS-tolerant bacteria from sewage water in Peshawar, KPK, Pakistan. It was concluded that all the TCS-resistant isolates were multidrug resistant (MDR) gram-negative rod-shaped bacteria, mostly belonging to the Enterobacteriaceae family.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.3
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• pp.487-493
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• 2004

This study has been undertaken to increase availability of native camellia in Jeonnam as a medicinal resource and to isolate the effective components from them. Fresh leaf and flower of camellia, single camellia tea and camellia tea mixed with green tea, herbs were screened for cytotoxicity on MCF -7 (human breast adenocarcinoma pleual effusion), Calu-6 (human pulmonary carcinoma), SNU-601 (human gastric carcinoma) cells. Also their multidrug-resistance reversing activity were evaluated using drug sensitive AML-2/WT and multidrug-resistant AML-2/D100 cells. Among the camellia extracts, young leaf and camellia tea mixed with green tea had strong growth inhibitory effects in below 100 $\mu\textrm{g}$/mL against human cancer cells. In result, young leaf showed the strongest inhibitory effects on MCF -7 ($IC_{50}$/ = 100 $\mu\textrm{g}$/mL ↑), Calu-6 ($IC_{50}$/ = 79 $\mu\textrm{g}$/mL), and SNU -601 ($IC_{50}$/ = 39 $\mu\textrm{g}$/mL), and AML-2/WT ($IC_{50}$/ = 64 $\mu\textrm{g}$/mL). Chemosensitizing effect was the extracts of mature leaf ($IC_{50}$/ = 97 $\mu\textrm{g}$/mL, RF=3.0), roasted tea ($IC_{50}$/ = 76 $\mu\textrm{g}$/mL, RF = 2.6 ↑) and steam tea ($IC_{50}$/ = 70 $\mu\textrm{g}$/mL, RF=2.8 ↑) strongly potentiate vincristine cytotoxicity in AML-2/D100 cells. But their cytotoxicities to both sensitive AML-2/WT and resistant AML-2/D100 cells were in the same order of magnitude. This results indicate that crude extracts of camellia mature leaves would contain some principles which have chemosensitizing activity.

• Tuberculosis and Respiratory Diseases
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• v.60 no.4
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• pp.404-411
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• 2006

Purpose : Multidrug-resistant tuberculosis (MDR-TB) is an emerging threat to human beings. However, there is little data on the current status of MDR-TB in Korea. This study investigated the current status of MDR-TB in Korea using a survey of all the data from drug susceptibility tests (DST) performed across the country over the last three years. Method : The DST results between Jan. 2000 and Dec. 2002 from 7 laboratories, which were in charge of all antituberculous DSTs across the country as of March 2002, were collected and analyzed to determine the actual number of drug-resistant or MDR-TB patients, annual trend, degree and pattern of resistance against anti-TB drugs, etc. Results : Six laboratories used the absolute concentration method for DST and one used the proportional method. 59, 940 tests had been performed over the 3 year study period. The number of DST performed annually was 18,071, 19,950, and 21,919 in 2000-2002, respectively. The number of resistant tuberculosis patients (resistant against at least one anti-TB drug) had increased by 16.9% from 6,338 in 2000 to 7,409 in 2002. The rate of resistant tuberculosis among all DST results was 35.1% in 2000, 34.5% in 2001, and 33.8% in 2002. The number of MDR-TB patients (resistant against at least both isoniazid and rifampin) showed an increasing trend (14.5%) from 3,708 in 2000 to 4,245 in 2002. Conclusion : Approximately 4,000 MDR-TB cases are newly identified by DST annually and the number is showing an increasing trend. This study suggests that in order to cope with the current MDR-TB situation, the DST methods will need to be standardized and more aggressive measures will be required.

• The Korean Journal of Nuclear Medicine
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• v.38 no.1
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• pp.85-98
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• 2004

Purpose: Cellular uptake of $^{99}mTc$-sestamibi (MIBI) and $^{99}mTc$-tetrofosmin (TF) is low in cancer cells expressing multidrug resistance(MDR) by p-glycoprotein(Pgp) or multidrug related protein(MRP). Verapamil is known to increase cellular uptake of MIBI in MDR cancer cells, but is recently reported to have different effects on tracer uptake in certain cancer cells. This study was prepared to evaluate effects of verapamil on cellular uptake of MIBI and TF in several cancer cells. Materials and Methods: Celluar uptakes of Tc-99m MIBI and TF were measured in erythroleukermia K562 cell, breast cancer MCF7 cell, and human ovarian cancer SK-OV-3 cells, and data were compared with those of doxorubicin-resistant K562(Ad) cells. RT-PCR and Western blot analysis were used for the detection of mdr1 mRNA and Pgp expression, and to observe changes in isotypes of PKC enzyme. Effects of verapamil on MIBI and TF uptake were evaluated at different concentrations upto $200{\mu}M\;at\;1{\times}10^6\;cells/ml\;at\;37^{\circ}C$. Radioactivity in supernatant and pellet was measured with gamma counter to calculate cellular uptake ratio. Toxicity of verapamil was measured with MTT assay. Results: Cellular uptakes of MIBI and TF were increased by time in four cancer cells studied. Co-incubation with verapamil resulted in an increase in uptake of MIBI and TF in K562(Adr) cell at a concentration of $100{\mu}M$ and the maximal increase at $50{\mu}M$ was 10-times to baseline. In contrast, uptakes of MIBI and TF in K562, MCF7, SK-OV3 cells were decreased with verapamil treatment at a concentration over $1{\mu}M$. With a concentration of $200{\mu}M$ verapamil, MIBI and TF uptakes un K562 cells were decreased to 1.5 % and 2.7% of those without verapamil, respectively. Cellular uptakes of MIBI and TF in MCF7 and SK-OV-3 cells were not changed with $10{\mu}M$, but were also decreased with verapamil higher than $10{\mu}M$, resulting 40% and 5% of baseline at $50{\mu}M$. MTT assay of four cells revealed that K562, MCF7, SK-OV3 were not damaged with verapamil at $200{\mu}M$. Conclusion: Although verapamil increases uptake of MIBI and TF in MDR cancer cells, cellular uptakes were further decreased with verapamil in certain cancer cells, which is not related to cytotoxicity of drug. These results suggest that cellular uptakes of both tracers might differ among different cells, and interpretation of changes in tracer uptake with verapamil in vitro should be different when different cell lines are used.

• Tuberculosis and Respiratory Diseases
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• v.55 no.1
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• pp.41-58
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• 2003

Background : The resurgence of tuberculosis and the widespread emergence of multidrug-resistant M. tuberculosis have emphasized the importance of rapid and accurate diagnostic procedures. Recently, the oligonucleotide chip has proven to be a useful tool in the rapid diagnosis of infectious diseases. The purpose of this study was to rapidly and accurately detect specific mutations in the rpoB, katG and rpsL genes associated with rifampin, isoniazid and streptomycin resistance in M. tuberculosis, respectively, using a single oligonucleotide chip. Method : For detection of drug-resistance, 7 wild-type and 13 mutant-type probes for rifampin, 2 wild-type and 3 mutant-type probes for isoniazid, and 2 wild-type and 2 mutant-type probes for streptomycin were designed and spotted onto glass slides. Fifty-five cultured samples of M. tuberculosis were amplified by PCR, and then underwent hybridization and scanning. Direct sequencing was done to verify the results from the oligonucleotide chip and to analyze the types of mutations. Result : Thirty-five cases out of 40 rifampin-resistant strains(~88%) had mutations in the rpoB gene. One case had a new mutation(D516F, GAC R TTC) and another known mutation together. Twenty cases out of 42 isoniazid-resistant strains(~50%) had mutations in the katG gene, while 7 cases out of 9 streptomycin-resistant strains(~78%) had mutations in the rpsL gene. From these results, the oligonucleotide chip was confirmed to be able to detect the most frequent mutations from the genes associated with rifampin, isoniazid and streptomycin resistance. The results proved that the drug-resistance detection probes were specific. When the results from the oligonucleotide chip and DNA sequencing were compared, the types of mutations were exactly matched. Conclusion : The diagnostic oligonucleotide chip with mutation specific probes for drug resistance is a very reliable and useful tool for the rapid and accurate diagnosis of drug resistance against rifampin, isoniazid and streptomycin in M. tuberculosis infections.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5451-5454
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• 2012

Objective: The objective of this study was to evaluate the association of MDR1 gene polymorphisms with susceptibility to hepatocellular carcinoma (HCC). Methods: A total of 689 HCC patients and 680 cancer-free subjects were enrolled. Human MDR1 gene polymorphisms were investigated by created restriction site-polymerase chain reaction (CRS-PCR) and DNA sequencing methods. Multiple logistic regression models were applied to estimate the association between MDR1 gene polymorphisms and susceptibility to HCC. Results: We detected a novel c.4125A>C polymorphism and our findings suggested that this variant was significantly associated with susceptibility to HCC. A significantly increased susceptibility to HCC was noted in the homozygote comparison (CC versus AA: OR=1.621, 95% CI 1.143-2.300, ${\chi}^2$=7.4095, P=0.0065), recessive model (CC versus AC+AA: OR=1.625, 95% CI 1.167-2.264, ${\chi}^2$=8.3544, P=0.0039) and allele contrast (C versus A: OR=1.185, 95% CI 1.011-1.389, ${\chi}^2$=4.4046, P=0.0358). However, no significant increase was observed in the heterozygote comparison (AC versus AA: OR=0.995, 95% CI 0.794-1.248, ${\chi}^2$=0.0017, P=0.9672) and dominant model (CC+AC versus AA: OR=1.106, 95% CI 0.894-1.369, ${\chi}^2$=0.8560, P=0.3549). Conclusions: These findings suggest that the c.4125A>C polymorphism of the MDR1 gene might contribute to susceptibility to HCC in the Chinese population. Further work will be necessary to clarify the relationship between the c.4125A>C polymorphism and susceptibility to HCC on larger populations of diverse ethnicity.

• Archives of Plastic Surgery
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• v.34 no.6
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• pp.691-696
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• 2007

Purpose: The emergency of multi-drug resistant stains of bacteria represents a challenge in the field of plastic surgery. Especially, MRSA(methycillin-resistant Staphylococcus aureus) and Pseudomonas aeruginosa have strong pathogenicity as well as multi-drug resistance so that they have become a lot more problematic strains. This study has been planned to reduce the bacterial burden by applying $Acticoat^{(R)}$(Smith & Nephew Healthcare, Hull, England)dressing into the chronic wounds infected by multi-drug resistant strains and to facilitate their healing. Methods: Nanocrystalline silver dressings($Acticoat^{(R)}$) were applied to chronic wound infected by MRSA or Pseudomonas aeruginosa. Multi-drug resistant bacteria were smeared over a slide glass using sterilized cotton swabs and gram stains were performed directly before and after applying $Acticoat^{(R)}$ dressings at 1, 24, 48 and 72 hours. The gram-stained slides were observed using an optical microscope magnified 1000 times(${\times}1000$). The bacterial counts of the control group(0 hour) were compared to those of the experimental groups(1, 24, 48, and 72 hour). Paired T-test was used to assess a statistical significance. MRSA was cultured in two BAPs(blood agar plate) and two MacConkey plates with streak plate method. None were interventions on one culture plate, while on the other culture plate, $Acticoat^{(R)}$ was placed in a square shape and cultured for 72 hours at $37^{\circ}C$, then plates were examined. Pseudomonas aeruginosa was cultured in the same manner as MRSA. Results: There are the large amount of declination of bacterial counts with statistical significance after $Acticoat^{(R)}$ dressing. The bacteria grew in culture plate without specific intervention, but no bacteria grew in culture plate with applying of $Acticoat^{(R)}$ dressing. Conclusion: We believe that $Acticoat^{(R)}$ dressing could be used as an effective method of treating chronic wounds which are infected by multi-drug resistant organisms.