• Title/Summary/Keyword: E-MDR

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Reversal of Resistance towards Cisplatin by Curcumin in Cervical Cancer Cells

  • Roy, Madhumita;Mukherjee, Sutapa
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.3
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    • pp.1403-1410
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    • 2014
  • Epigenetic regulators like histone deacetylases (1 and 2), and viral onco-proteins (E6/E7) are known to be overexpressed in cervical cancer cells. The present study was designed to investigate the effect of curcumin on HDACs (1 and 2) and HPV E6/E7 in the cervical cancer cell line SiHa and a drug resistant clone $SiHa^R$ (derived from SiHa). It was further intended to investigate whether curcumin could sensitize the cells towards cisplatin induced cell killing by modulation of multi drug resistant proteins like MRP1 and Pgp1. Curcumin inhibited HDACs, HPV expression and differentially increased acetylation and up-regulation of p53 in SiHa and $SiHa^R$, leading to cell cycle arrest at G1-S phase. Up-regulation of pRb, p21, p27 and corresponding inhibition of cyclin D1 and CDK4 were observed. Cisplatin resistance in $SiHa^R$ due to over-expression of MRP1 and Pgp1 was overcome by curcumin. Curcumin also sensitized both the cervical cancer cells towards cisplatin induced cell killing. Inhibition of HDACs and HPVs led to cell cycle arrest at G1/S phase by alteration of cell cycle regulatory proteins. Suppression of MRP1 and Pgp1 by curcumin resulted in sensitization of cervical cancer cells, lowering the chemotherapeutic dose of the drug cisplatin.

Mutations of katG and inhA in MDR M. tuberculosis (국내에서 분리된 다제 내성 결핵균의 katG 와 inhA 변이 다양성 및 그 빈도)

  • Lin, Hai Hua;Kim, Hee-Youn;Yun, Yeo-Jun;Park, Chan Geun;Kim, Bum-Joon;Park, Young-Gil;Kook, Yoon-Hoh
    • Tuberculosis and Respiratory Diseases
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    • v.63 no.2
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    • pp.128-138
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    • 2007
  • Backgrounds: Mutations of katG and inhA (ORF and promoter) are known to be related to isoniazid (INH) resistance of Mycobacterium tuberculosis. Because reports on these mutations in Korean isolates are limited (i.e. only the frequency of katG codon 463 was evaluated.), we tried to know the kinds of mutations of two genes and their frequencies in INH resistant Korean M. tuberculosis strains. Methods: PCR was performed to amplify katG (2,223 bp), inhA ORF (-77~897, 975 bp), and inhA promoter (-168~80, 248 bp) from 29 multidrug resistant M. tuberculosis (MDR-TB) DNAs prepared by bead beater-phenol method. Their sequences were determined and analyzed by ABI PRISM 3730 XL Analyzer and MegAlign package program, respectively. Results: All of the isolates had more than one mutation in katG or inhA gene. Twenty seven (93%) of 29 tested strains had katG mutations, which suggests that katG is a critical gene determining INH resistance of M. tuberculosis. Amino acid substitutions, such as Arg463Leu and Ser315Thr, due to point mutations of the katG were the most frequent (62.1% and 55.2%) mutations. In addition, deletion of the katG gene was frequently observed (17.2%). Analyzed Korean MDR-TB isolates also had variable inhA mutations. Point mutation of inhA promoter region, such as -15 ($C{\rightarrow}T$) was frequently found. Substitution of amino acid (Lsy8Asn) due to point mutation ($AAA{\rightarrow}AAC$) of inhA ORF was found in 1 isolate. Interestingly, 14 point mutated types that were not previously reported were newly found. While four types resulted in amino acid change, the others were silent mutations. Conclusions: Although it is not clear that the relationship of these newly found mutations with INH resistance, they show marked diversity in Korean MDR-TB strains. It also suggests their feasibility as a molecular target to supplement determining the INH resistance of clinical isolates because of the possible existence of low-level INH resistant strains.

Antimicrobial Resistance and Multi-Drug Resistance Patterns of Pathogenic Bacteria Isolated from Food Poisoning Patients in Incheon (인천지역 식중독 환자에서 분리한 병원성 세균의 항생제 내성 및 다제 내성 양상)

  • Huh, Myung-Je;Oh, Sung-Suck;Jang, Jae-Seon
    • The Korean Journal of Food And Nutrition
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    • v.26 no.1
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    • pp.132-136
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    • 2013
  • Antimicrobial resistance and multi-drug resistance patterns have been carried out on total of 210 isolated of Salmonella spp. and pathogenic E. coli isolated from food poisoning patients on January through December 2012 in Incheon, Korea. The highest percentage of antibiotics resistance was found to the following antimicrobial agents: tetracycline 43.8%, ampicillin 34.8%, nalidixic acid 23.8%, sulfamethoxazole/trimethoprim and chloramphenicol 12.4%, and ampicillin/sulbactam 11.4%. The highest percentage of resistance was 37.5% to ampicillin for Salmonella spp. and 59.0% to tetracycline for pathogenic E. coli. Overall the multidrug resistance rates of 1 drug was 26.2%, 2 drugs 9.0%, 3 drugs 9.5%, 4 drugs 7.1%, and 5 or more drugs 12.46%. The multi-drug (MDR) strains to four or more antimicrobial agents among the resistant organisms were quite high: 15.9% and 22.1% for Salmonella spp. and pathogenic E. coli, respectively. The study implies that limitation of unnecessary medication use is pertinent in order to maintaining the efficacy of drugs.

Nontyphoid Salmonella Prevalence, Serovar Distribution and Antimicrobial Resistance in Slaughter Sheep

  • Cetin, Ece;Temelli, Seran;Eyigor, Aysegul
    • Food Science of Animal Resources
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    • v.40 no.1
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    • pp.21-33
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    • 2020
  • This study aimed to determine the current prevalence, serovar distribution and antimicrobial resistance rate and patterns of nontyphoid Salmonella (NTS) in slaughter sheep and their edible offal. While filling the gap of up to date related information in Turkey, data presented is also of significance since contamination of ovine meat, its products and offal with this pathogen is threat to public health due to their considerably high consumption rates in our country. Current NTS carriage in 200 apparently healthy slaughter sheep by ISO 6579:2002, 6579:2002/A1:2007 standard bacteriology (ISO) was 5% (10/200) (4 fecal content - 2%, 3 mesenterial lymph node - 1.5%, 3 kidney - 1.5%) out of 1,400 samples (0.7%), with no isolation from carcass, liver, gallbladder, spleen. Real-time PCR was in substantial agreement to ISO in confirming Salmonella-suspect isolates (Relative Trueness: 93.6%). S. Newport (40%) was the predominant serovar, followed by the second prevalent serovars as S. Typhimurium and S. Kentucky (20%), and by S. Umbilo and S. Corvallis (10%). Four and 6 out of 10 NTS isolates were susceptible (40%) and resistant (60%) to 18 antimicrobials, respectively. S. Typhimurium isolates were multidrug resistant (MDR) to tigecycline and sulphamethoxazole/trimethoprim, with one also resistant to cefepime. S. Corvallis was MDR to ampicillin, ciprofloxacin, norfloxacin and pefloxacin. The predominance of S. Newport and first isolation of S. Corvallis in sheep in the world; first time isolations of Newport, Kentucky, Corvallis, Umbilo serovars from sheep in Turkey; and high antimicrobial resistance rates obtained in majority of the isolates highlights study findings.

Occurrence and Characteristics of Methicillin-Resistant and -Susceptible Staphylococcus aureus Isolated from the Beef Production Chain in Korea

  • Lee, Haeng Ho;Lee, Gi Yong;Eom, Hong Sik;Yang, Soo-Jin
    • Food Science of Animal Resources
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    • v.40 no.3
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    • pp.401-414
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    • 2020
  • The emergence and persistence of methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) in livestock animals have been reported as a potential risk factor for transmission to humans. In this study, we investigated the nationwide prevalence and characteristics of MRSA and MSSA in the Korean beef production system, including retail markets, slaughterhouses, and cattle farms. From a total of 1,285 samples, only 5 MRSA strains were isolated: from a farmer (1 ST72 MRSA), a carcass sample from a slaughterhouse (1 ST72 MRSA), and beef cattle (3 ST5 MRSA). In addition, 11 MSSA strains were isolated from beef cattle (n=3), humans (1 farmer, 1 slaughterhouse worker, and 4 retail market workers), and carcass samples (n=1) and slaughterhouse environment (n=1). Although the prevalence of MRSA and MSSA in beef cattle was much lower than that reported in pigs, 5/5 MRSA and 2/11 MSSA strains displayed multiple drug resistance (MDR) phenotypes. Unlike the swine-associated MRSA, no correlation was found between tetracycline/zinc resistance and MDR phenotype. However, MRSA strains had an identical set of staphylococcal enterotoxins and exhibited enhanced levels of resistance to antimicrobial peptides (PMAP-36 and LL-37) compared to the MSSA strains. In conclusion, continued and systemic surveillance of livestock, meat products, and humans in close contact with livestock/meat products is necessary to prevent the transmission of MRSA and MSSA to humans.

The Criticality Analysis of Spent Fuel Pool with Consolidated Fuel in KNU 9 & 10 (조밀화 집합체로 중간저장하는 경우 원자력 발전소 9, 10호기의 사용 후 핵연료 저장조의 임계분석)

  • Jae, Moo-Sung;Park, Goon-Cherl;Chung, Chang-Hyun;Jang, Jong-Hwa
    • Nuclear Engineering and Technology
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    • v.20 no.1
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    • pp.27-34
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    • 1988
  • Since the lack of the spent fuel storage capcity has been expected for all Korean nuclear power plants in the mid-1990s, the maximum density rack (MDR) with consolidated fuels can be proposed to overcome the shortage of the storage capacity in KNU 9 & 10 which have most limited capacities. To ensure the safety when the alternatives are applied in the KNU 9 & 10, the multiplication factor are calculated with varying the rack pitch and the thickness of consolidated storage box by the AMPX-KENO IV codes. The computing system is verified by the benchmark calculation with criticality experiments for arrays of consolidated fuel modules, which was reported by B & W in 1981. Also an abnormal condition, i.e. malposition accident, is simulated. The results indicate that the KNU 9 & 10 storage pools with consolidated fuel are safe in the view of the criticality. Thus the storage capacity can be expanded from 9/3 cores into 27/3 cores even with considering equipments and cooling spaces.

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Livestock-associated methicillin-resistant Staphylococcus aureus in Korea: antimicrobial resistance and molecular characteristics of LA-MRSA strains isolated from pigs, pig farmers, and farm environment

  • Back, Seung Hyun;Eom, Hong Sik;Lee, Haeng Ho;Lee, Gi Yong;Park, Kun Taek;Yang, Soo-Jin
    • Journal of Veterinary Science
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    • v.21 no.1
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    • pp.2.1-2.14
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    • 2020
  • The emergence of livestock-associated (LA)-methicillin-resistant Staphylococcus aureus (MRSA) in livestock animal has become a significant zoonotic concern. In the present study, we investigated nationwide prevalence of LA-MRSA across pork production chain including pig farms, slaughterhouses, and retail markets. A total of 40 MRSA strains were isolated during the investigation and the overall prevalence of MRSA was 3.4% (n = 37), 0.6% (n = 2), and 0.4% (n = 1) in pig farms, slaughterhouses, and retail markets, respectively. Multilocus sequence typing analyses revealed that the 2 most significant clonal lineages in pork production chain in Korea were ST398 (n = 25) and ST541 (n = 6). All of the 40 MRSA isolates were further characterized to investigate key genotypic and phenotypic correlates associated with the emergence and spread of clonal complex 398 (CC398; ST398, and ST541) LA-MRSA. Although the prevalence of swine-associated MRSA was still relatively low and mostly restricted to pig farms, multidrug-resistant CC398 LA-MRSA isolates with new spa types (t18102 and t18103) were identified as a major clonal lineage. The CC398 LA-MRSA strains tended to exhibit increased levels of multiple drug resistance (MDR) phenotype compared with non-CC398 MRSA strains. Of note, in comparison with non-CC398 MRSA isolates, CC398 LA-MRSA isolates exhibited significantly enhanced tetracycline (TET) and zinc resistance. These findings suggested that co-selection pressure associated with MDR phenotype, especially TET resistance, and zinc resistance may have played a significant role in the emergence and persistence of CC398 LA-MRSA in pig farms in Korea.

Evaluation of the Antimicrobial Activities of 35 Seaweed Extracts against Pathogenic Bacteria and Candida sp. (35종 해조류 추출물의 병원성 세균 및 Candida sp. 진균에 대한 항균 활성 평가)

  • Kim, Mi-Sun;Kwon, Kyung-Jin;Lee, Min-Jin;Ahn, Seon-Mi;Sohn, Ho-Yong
    • Microbiology and Biotechnology Letters
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    • v.40 no.2
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    • pp.144-151
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    • 2012
  • In the course of this study aimed at the development of functional food ingredients from seaweeds, the in vitro antimicrobial activities of methanol extracts prepared from 35 different seaweeds (17 phaeophyta, 11 rhodophyta and 7 chlorophyta) were determined against food-borne diseases and pathogenic microorganisms including multi-drug resistant (MDR) Pseudomonas sp. and Candida sp. Based on disc-diffusion assays at 500 g/disc concentration of the methanol extracts, Ishige okamurai, I. foliacea, Sargassum confusum, and S. yamade exhibited strong antibacterial activities in a broad-spectrum, except against Pseudomonas aeruginosa. In addition to the latter four seaweeds, Ecklonia stolonifera, E. cava and Eisenia bicyclis also demonstrated antifungal activity against C. albicans. Among these 8 selected seaweeds, I. okamurai, I. foliacea, and S. yamade exhibited strong hemolytic activity (55-93%) at 500 g/ml against human RBC. Organic solvent sequential fractions using hexane, ethylacetate and butanol, and water residues were prepared from the 8 selected seaweeds and their anti-Candida sp. activities were further determined. The ethylacetate and butanol fraction of I. okamurai, and the hexane fraction of I. foliacea demonstrated antifungal activity against MDR-pathogenic Candida sp. Although the solvent fractions had no activity against MDR-Pseudomonas sp., our results suggest that seaweeds, especially Ishige okamurai, I. foliacea, S. confusum, and S. yamade could be developed as broad-spectrum antimicrobial ingredients.

Isolation frequency and antimicrobial resistance of Escherichia coli & Enterococcus spp. isolated from beef & pork on sale in Seoul, Korea (서울지역에서 유통 중인 쇠고기와 돼지고기로부터 분리된 대장균과 장구균의 분리율 및 항생제 내성)

  • Kim, Ju-Young;Park, Mi-Ae;Kim, Jee-Eun;Chae, Hee-Sun;Park, Yeon-Jae;Son, Jang-Won;Yang, Yun-Mo;Choi, Tae-Seok;Lee, Ju-Hyung
    • Korean Journal of Veterinary Service
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    • v.36 no.2
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    • pp.111-119
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    • 2013
  • The aim of this study was to investigate the isolation frequency and antimicrobial resistance of Escherichia coli (E. coli) and Enterococcus spp. from domestic beef and pork on sale in Seoul, Korea. A total of 106 (10.4%) E. coli and 114 (11.2%) Enterococcus spp. from 635 domestic beef and 381 pork samples were isolated and examined for susceptibility to 15 and 11 antimicrobial agents, respectively. The most frequent antimicrobial resistance observed in E. coli isolates was to ampicillin (38.6%), followed by streptocmycin (34.9%) and tetracycline (32.0%). The most frequent antimicrobial resistance in E. faecium isolates was to erythromycin (53.8%) and rifampin (46.1%), and in E. faecalis isolates was to tetracycline (55.7%) and rifampin (55.0%). Among the isolates, multi-drug resistant (MDR) E. coli and Enterococcus spp. strains showing resistances to more than two antimicrobial agents tested were 10.4% and 11.2%, respectively. As a result, appropriate protocols for antimicrobial agents and strategies to reduce antimicrobial resistance will be needed in future.

Sensitivity of Gastric Cancer Cells to Chemotherapy Drugs in Elderly Patients and Its Correlation with Cyclooxygenase-2 Expression

  • Qiu, Zhen-Qin;Qiu, Zhen-Rong
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.8
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    • pp.3447-3450
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    • 2015
  • Objective: To explore the sensitivity of gastric cancer cells to chemotherapy drugs in elderly patients and its correlation with cyclooxygenase-2 (COX-2) expression in cancer tissue. Materials and Methods: Forty-three elderly patients with gastric cancer (observation group) and 31 young patients with gastrointestinal tumors (control group) who were all diagnosed by pathology and underwent surgery in the 89th Hospital of Chinese People's Liberation Army were selected. Drug sensitivity testing of tumor cells in primary culture was carried out in both groups using a methyl thiazolyl tetrazolium (MTT) method, and the expression of COX-2 and the factors related to multi-drug resistance (MDR) in cancer tissue were assessed by immunohistochemistry. Results: The inhibition rates (IR) of vincristine (VCR), 5-fluorouracil (5-FU), oxaliplatin (L-OHP), mitomycin (MMC) and epirubicin (eADM) on tumor cells in the observation group were dramatically lower than in the control group, with statistical significance (P<0.05 or P<0.01). The positive rates of COX-2, glutathione s-transferase-${\pi}$ (GST-${\pi}$) and P glycoprotein (P-gp) expression in cancer tissue in the observation group were all higher than in control group (P<0.05), while that of DNA topoisomerase $II{\alpha}$ ($TopoII{\alpha}$) expression lower than in the control group (P<0.01). In the observation group, COX-2 expression in cancer tissue had a significantly-positive correlation with GST-${\pi}$ and P-gp (r=0.855, P=0.000; r=0.240, P=0.026), but a negative correlation with $TopoII{\alpha}$ (r=-0.328, P=0.002). In the control group, COX-2 expression in cancer tissue was only correlated with P-gp positively (r=0.320, P=0.011). Bivariate correlation analysis displayed that COX-2 expression in cancer tissue in the observation group had a significantly-negative correlation with the IRs of 5-FU, L-OHP, paclitaxel (PTX) and eADM in tumor cells (r=-0.723, P=0.000; r=-0.570, P=0.000; r=-0.919, P=0.000; r=-0.781, P=0.000), but with hydroxycamptothecine (HCPT), VCR and 5-FU in the control group (r=-0.915, P=0.000; r=-0.890, P=0.000; r=-0.949, P=0.000). Conclusions: Gastric cancer cells in elderly patients feature stronger MDR, which may be related to high COX-2 expression.