• Title/Summary/Keyword: Multidrug-resistant

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Cytotoxicity and Chemosensitizing Effect of Camellia(Camellia japonica) Tea Extracts (동백엽차와 화차의 세포독성 및 다제내성 극복효과)

  • 황은주;차영주;박민희;이장원;이숙영
    • 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.

Bronchoscopic Diagnosis in ICU Patient Accompanying Pneumonia (폐렴이 동반된 중환자실 환자에 대한 기관지내시경적 진단)

  • Chang, Jung Hyun
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.1
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    • pp.114-123
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    • 1997
  • Background : To assess the diagnostic role of bronchoscopic lavage for the evaluation of pneumonia in intensive care unit(ICU), the results were compared to blind endobronchial specimen. Method : From September 1993 to August 1996, twenty-eight ICU patients suspected pneumonia on the basis of clinical evidence and performed bronchoscopy under the diagnostic or therapeutic purpose were studied retrospectively for the clinical findings including culture of bronchoscopic and blind endobronchial specimen. Bronchoscopic specimen was got through small amount of bronchoalveolar lavage with 20-40ml saline, one or two times on the suspected site. Results : l. Main reasons of ICU admission were respiratory and impending respiratory failure Nosocomial pneumonia was most common with 16 cases; each for community acquired and immunocompromised type with 6 cases. Diagnostic purpose of bronchoscopy was performed in 20 cases as 71 percent in total, whereas therapeutic removal of secretion in 8 cases. The complication during bronchoscopic evaluation was trivial. 2. The agreement between blind endobronchial and bronchoscopic specimen on microbial culture was only 39.3 percent. However, 2 cases each for aspergillosis and tuberculosis were diagnosed under bronchoscopic evaluation. 3 The application of mechanical ventilation occured significantly frequently in multidrug resistant pneumonia compared with other pneumonia in terms of bronchoscopic specimen. 4. The application of mechanical ventilation was significantly common in nosocomial pneurmonia compared with other types of pneumonia. Conclusion : The selective bronchoalveolar lavage and therapeutic removal of bronchial secretion with bronchoscopy in ICU patient accompanying pneumonia is a very useful tool with safety. The multidrug resistant pneumonia or nosocomial pneumonia could be closely associated with the use of mechanical ventilation.

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Mechanistic Analysis of Taxol-induced Multidrug Resistance in an Ovarian Cancer Cell Line

  • Wang, Ning-Ning;Zhao, Li-Jun;Wu, Li-Nan;He, Ming-Feng;Qu, Jun-Wei;Zhao, Yi-Bing;Zhao, Wan-Zhou;Li, Jie-Shou;Wang, Jin-Hua
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.9
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    • pp.4983-4988
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    • 2013
  • Objectives: To establish a taxol-resistant cell line of human ovarian carcinoma (A2780/Taxol) and investigate its biological features. Methods: The drug-resistant cell line (A2780/Taxol) was established by continuous stepwise selection with increasing concentrations of Taxol. Cell morphology was assessed by microscopy and growth curves were generated with in vitro and in vivo tumor xenograft models. With rhodamine123 (Rh123) assays, cell cycle distribution and the apoptotic rate were analyzed by flow cytometry (FCM). Drug resistance-related and signal associated proteins, including P-gp, MRPs, caveolin-1, PKC-${\alpha}$, Akt, ERK1/2, were detected by Western blotting. Results: A2780/Taxol cells were established with stable resistance to taxol. The drug resistance index (RI) was 430.7. Cross-resistance to other drugs was also shown, but there was no significant change to radioresistance. Compared with parental cells, A2780/Taxol cells were significantly heteromorphous, with a significant delay in population doubling time and reduced uptake of Rh123 (p<0.01). In vivo, tumor take by A2780 cells was 80%, and tumor volume increased gradually. In contrast, with A2780/Taxol cells in xenograft models there was no tumor development. FCM analysis revealed that A2780/Taxol cells had a higher percentage of G0/G1 and lower S phase, but no changes of G2 phase and the apoptosis rate. Expression of P-gp, MRP1, MRP2, BCRP, LRP, caveolin-1, PKC-${\alpha}$, Phospho-ERK1/2 and Phospho-JNK protein was significantly up-regulated, while Akt and p38 MARK protein expression was not changed in A2780/Taxol cells. Conclusion: The A2780/Taxol cell line is an ideal model to investigate the mechanism of muti-drug resistance related to overexpression of drug-resistance associated proteins and activation of the PKC-${\alpha}/ERK$ (JNK) signaling pathway.

Knowledge and Education Needs Related to Multidrug Resistant Organisms Infection Control among Small and Medium Size Hospital (중소병원 간호사의 다제내성균 감염관리 지식 및 교육요구도)

  • Lee, Mi Hyang
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.21 no.4
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    • pp.463-470
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    • 2020
  • This study was conducted to aid in the development of an infection control educational program for nurses, by assessing the knowledge and educational demand of nurses for MDRO infection control. Totally, 115 nurses participated in the study. Data were collected from November 15-30, 2019, using structured questionnaires. Descriptive statistics, t-test, and ANOVA were applied for analyzing the data. Experience of caring for MDRO patients was reported by 86.1% nurses, whereas 67.8% nurses had received training on MDROs. The average score for knowledge on MDROs was 25.51 out of 27 points, with minimal correct answers given for the query on level of disinfection for medical equipment used by patients, criteria for the preemptive precaution, patient management in the cohort, and timing for removing personal protective equipment. The educational demand was highest for assignment to the precaution, criteria for screening examination, and management of outbreak. Also, educational needs differed with respect to the general educational characteristics and position of the individual. We propose the need to differentiate the educational status according to the career when developing the MDROs program, and the necessity to execute education of MDROs for new nurses and career nurses.

Molecular Characterization and Antimicrobial Susceptibility of Biofilm-forming Acinetobacter baumannii Clinical Isolates from Daejeon, Korea (대전지역에서 분리된 생물막 형성 Acinetobacter baumannii 임상분리주의 분자유전학적 특성과 항균제 감수성양상)

  • Sung, Ji Youn
    • Korean Journal of Clinical Laboratory Science
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    • v.50 no.2
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    • pp.100-109
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    • 2018
  • The emergence and dissemination of multidrug-resistant (MDR) Acinetobacter baumannii isolates have been reported worldwide, with most of these possessing the ability to form biofilms. Biofilm formation is an important virulence factor associated with the resistance to disinfection and desiccation. This study examined the genetic basis of antimicrobial resistance mechanisms of biofilm-forming A. baumannii clinical isolates. Imaging and quantification of biofilms were performed by a crystal violet assay and 46 biofilm-forming A. baumannii isolates were selected. Subsequently, 16 isolates belonging to different clones were identified using REP-PCR, and detection of the antimicrobial determinants in the isolates was carried out. The 16 isolates included 9 non-MDR and 7 MDR isolates. The mean biomass $OD_{560}$ values of the non-MDR (0.96) and MDR (1.05) isolates differed but this difference was not significant. In this study, most biofilm-forming MDR A. baumannii isolates contained various antimicrobial resistance determinants ($bla_{OXA-23}$, armA, and mutations of gyrA and parC). On the other hand, most biofilm-forming non-MDR A. baumannii isolates did not contain antimicrobial resistance determinants. These results suggest that there is little correlation between the biofilm-forming ability and antimicrobial susceptibility in A. baumannii isolates. In addition, the emergence of MDR A. baumannii clinical isolates is generally caused by mutations of the genes associated with antimicrobial resistance and/or the acquisition of various antimicrobial resistance determinants.

Ginsenoside Rg5 overcomes chemotherapeutic multidrug resistance mediated by ABCB1 transporter: in vitro and in vivo study

  • Feng, Sen-Ling;Luo, Hai-Bin;Cai, Liang;Zhang, Jie;Wang, Dan;Chen, Ying-Jiang;Zhan, Huan-Xing;Jiang, Zhi-Hong;Xie, Ying
    • Journal of Ginseng Research
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    • v.44 no.2
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    • pp.247-257
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    • 2020
  • Background: Multidrug resistance (MDR) to chemotherapy drugs remains a major challenge in clinical cancer treatment. Here we investigated whether and how ginsenoside Rg5 overcomes the MDR mediated by ABCB1 transporter in vitro and in vivo. Methods: Cytotoxicity and colon formation as well as the intracellular accumulation of ABCB1 substrates were carried out in MDR cancer cells A2780/T and A549/T for evaluating the reversal effects of Rg5. The expressions of ABCB1 and Nrf2/AKT pathway were determined by Western blotting. An A549/T cell xenograft model was established to investigate the MDR reversal activity of Rg5 in vivo. Results: Rg5 significantly reversed ABCB1-mediated MDR by increasing the intracellular accumulation of ABCB1 substrates without altering protein expression of ABCB1. Moreover, Rg5 activated ABCB1 ATPase and reduced verapamil-stimulated ATPase activity, suggesting a high affinity of Rg5 to ABCB1 binding site which was further demonstrated by molecular docking analysis. In addition, co-treatment of Rg5 and docetaxel (TXT) suppressed the expression of Nrf2 and phosphorylation of AKT, indicating that sensitizing effect of Rg5 associated with AKT/Nrf2 pathway. In nude mice bearing A549/T tumor, Rg5 and TXT treatment significantly suppressed the growth of drug-resistant tumors without increase in toxicity when compared to TXT given alone at same dose. Conclusion: Therefore, combination therapy of Rg5 and chemotherapy drugs is a strategy for the adjuvant chemotherapy, which encourages further pharmacokinetic and clinical studies.

gyrA Mutations Found Among Ofloxacin-resistant Mycobacterium tuberculosis is Isolated from Korea

  • Kim Junho;Kim Yeun;Bae Kiho;Song Taek-Sun;Cho Sang-Nae;Lee Hyeyoung
    • Biomedical Science Letters
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    • v.11 no.4
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    • pp.465-471
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    • 2005
  • Ofloxacin has antimycobacterial activity that possibly contributes a pivotal role in the second-line drug regimens that are used for the treatment of multidrug-resistant tuberculosis. However, in some communities, the resistance rate of Mycobacterium tuberculosis to this agent is surging. Therefore, a rapid and accurate method that can be used to determine the resistance of M tuberculosis to the ofloxacin can be very useful for effective treatment of the patients. As an effort to develop such a method, this study was set up to reveal general types of mutations that are related to ofloxacin resistance of M tuberculosis. From previous studies, it has been well known that ofloxacin resistance is associated with mutations in a gene encoding the gyrase A subunit protein. In this study, we obtained 43 ofloxacin-resistant and 50 ofloxacin-susceptible M tuberculosis clinical isolates from Masan National TB Hospital, and sequences of DNA fragment of 320 bp, region of gyrA corresponding to the ofloxacin resistance-determining region were analyzed. In brief, the results showed that a total of seven mutation types were found at gyrA. Theses mutations were all clustered within nucleotides 2574 to 2586 of the gyrA gene (codons 88 to 94). Codon 94 was the most frequently substituted site. Twenty-four of the 43 isolates had mutations at this position resulting in a total of five different types of amino acid changes $(Asp{\to}Ala,\;Asp{\to}Gly,\;Asp{\to}His,\;Asp{\to}Tyr,\;and\;Asp{\to}Asn)$. Five isolates contained a mutation at codon 90 resulting $Ala{\to}Val$ change. Four isolates had mutations at codon 91 causing a $Ser{\to}Pro$ change at this site. Two isolates contained a mutation at codon 88 and each of them resulted in different types of amino acid changes $(Gly{\to}Cys,\;Gly{\to}Ala)$. On the other hand, polymorphic site at codon 95 was found in both ofloxacin-resistant and ofloxacin-susceptible isolates. From these results, we concluded that the rate of mutations present in gyrA among ofloxacin-resistant M. tuberculosis in Korea is similar to the general rates of mutations found throughout the world. Subsequently, an oligonucleotide probe was designed based on the results of sequence analysis and was used to develop a dot blot hybridization assay system to determine ofloxacin-resistance of M tuberculosis. To evaluate this probe, dot-blot hybridization was carried out using other 57 clinical isolates, and the results showed that the dot-blot hybridization assay is good for detecting sequence alterations atgyrA gene.

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Increasing Rates of Community Associated Methicillin-Resistant Staphylococcus aureus in Children with Muscular-Skeletal Infections in Korea: A Single Center Experience from 2000 to 2012 (소아의 근골격계 감염에서 지역사회 관련 메치실린 내성 황색 포도알균의 증가: 2000년 9월-2012년 8월간의 단일기관 연구)

  • Park, Jae-Hong;Lee, Taek-Jin
    • Pediatric Infection and Vaccine
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    • v.20 no.2
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    • pp.63-70
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    • 2013
  • Purpose : This study aimed to explore how prevalent the community-related methicillin-resistant Staphylococcus aureus (CA-MRSA) was in children with muscular-skeletal infections. Methods : We retrospectively reviewed the medical records of patients of 18 years or under who were diagnosed with suppurative arthritis or osteomyelitis and S. aureus from September 2000 through August 2012 at the CHA Bundang Medical center. Results : Thirty-one cases of suppurative arthritis or osteomyelitis were identified. The patients were between 17 days old and 18 years old with an average age of 7. Eleven cases (33.5%) of suppurative arthritis and 16 cases (51.6%) of osteomyelitis were observed. Five cases were accompanied by the two diseases. Methicillin sensitive S. aureus (MSSA) was isolated in 25 cases (80.6%) and methicillin resistant S. aureus (MRSA) was isolated in 6 cases (19.4%). Multidrug resistant strains were not observed. MRSA was not found from 2000 through 2005. All patients were treated with antibiotics and the duration of antibiotics treatment was $26.4{\pm}12.7$ days. Vancomycin was used as the initial antibiotic treatment in 4 cases (12.9%) and vancomycin was used as the definitive antibiotics in the 10 cases (32.3%). Conclusions : The result of this study showed that methicillin resistance rate of S. aureus from muscular-skeletal infections was concentrated in the latter half of the 12 year period.

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H2O2 Generating Ability and Multi-Drug Resistance of Lactic Acid Bacteria Required for Long-Term Inpatient Treatment with Antibiotic Resistance

  • Yuk, Young Sam
    • International journal of advanced smart convergence
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    • v.11 no.4
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    • pp.227-239
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    • 2022
  • Purpose: In our study, in order to find lactic acid bacteria (LAB) with multi-drug resistance to antibiotics, we isolated 140 strains from 15 types of kimchi commercially available in Korea and 20 types of Kimchi made at home from January to December in 2016, and investigated their H2O2 generating ability and multi-drug resistance to antibiotics. Methods: In order to observe the H2O2 generation ability of LAB, we performed the experiment with methods such as Rabe, Hillier, and Kang. To test the antibacterial susceptibility of LAB, we used the disc agar diffusion method using MRS agar (Difco, USA) according to the CLSI and WHO test methods. There are 18 types of antibiotic discs used. Results: Out of the total numbers of 140 strains, 6 strains of Ent. Faecium, 25 strains of L. plantarum, 1 strain of L. rhamnosus, 3 strains of L. sakei, 1 strain of L. acidophilus, 1 strains St. thermophilus, and 7 of unidentified strains generated H2O2. The antibiotic susceptibility of Ent. Faecium indicated SXT, OX, NA, and E; and the antibiotic susceptibility of L. plantarum indicated NA; and the antibiotic susceptibility of St. thermophilus indicated NA, CC, RA, CTT, CM, and P ; and the antibiotic susceptibility of L. rhamnosus indicated SXT, VA, NA and CTT; and the antibiotic susceptibility of 6 strains of L. sakei indicated SXT, OX, NOR, NA, CTT and CIP, all indicating antibiotic resistance. In the case of multi-drug resistance to antibiotics for 53 strains of L. antarum, 8-drug resistance was the most common with 25 strains, followed by 7-drug-resistant strains with 18 strains, 9-drug-resistant strains with 4 strains, 6-drug-resistant strains with 3 strains, 5-drug-resistant strains with 2 strains, and 17-drug-resistant strains with 1 strain. In the case of multi-drug resistance to antibiotics for Ent. Faecium 27 strains, 9-drug resistance was most commonly identified as 9 strains, 8-drug resistance was identified as 6 strains, 7- and 11 drug resistances were identified as 4 strains each, and 4- and 6-drug resistances were identified as 1 strain each. Conclusion: Ent. Faecium, L. plantarum, L. rhamnosus, L. sakei, and St. thermophilus, shown to have anantibacterial activity in previous studies on LAB and shown to have and H2O2 generating ability, antibiotic resistance and multi-drug resistance in this study, are expected to be able to play an excellent role for long-term inpatients to use as an alternative to antibiotics and to cope with emerging antibiotic resistance.

Effect of Multidrug Resistance Gene-1 (mdr1) Overexpression on In-Vitro Uptake of $^{99m}Tc$-sestaMIBl in Murine L1210 Leukemia Cells (백혈병 세포에서 Multidrug Resistance Gene-1 (mdr1)의 과발현이 $^{99m}Tc$-sestaMIBl 섭취에 미치는 영향)

  • Chun, Kyung-Ah;Lee, Jae-Tae;Lee, Sang-Woo;Kang, Do-Young;Sohn, Sang-Kyun;Lee, Jong-Kee;Chung, June-Key;Jun, Soo-Han;Lee, Kyu-Bo
    • The Korean Journal of Nuclear Medicine
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    • v.33 no.2
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    • pp.152-162
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    • 1999
  • Purpose: To determine whether $^{99m}Tc$-MIBI is recognized by the multidrug resistant P-glycoprotein (Pgp), we have measured quantitatively $^{99m}Tc$-MIBI uptake in cancer cells. The effects of various Pgp reversing agents on cellular $^{99m}Tc$-MIBI uptake were also investigated in the presence of multidrug resistance gene-1 (mdr1 gene) overexpression. Materials and Methods: We measured percentage uptake of $^{99m}Tc$-MIBI at different incubation temperatures both in mdr1 positive and negative cells. The effects of verapamil, cyclosporin, and dipyridamole on cellular uptake of $^{99m}Tc$-MIBI were also evaluated with or without overex-pression of mdr1 gene in cultured murine leukemia Ll210 cells. Results: The mdr1 gene expressing cell lines were effectively induced in in vitro with continuous application of low-dose adriamycin or vincristine. Cellular uptake of $^{99m}Tc$-MIBI was higher in mdr1 negative Ll210 cells than those of mdr1 positive cells, and higher when incubated in $37^{\circ}C$ than $4^{\circ}C$. In the presence of verapamil, cyclosporin or dipyridamole, $^{99m}Tc$-MIBI uptake was increased upto 604% in mdr1 positive cells. Conclusion: Cellular uptake of $^{99m}Tc$-MIBI is lower in leukemia cells over-expressing mdr1 gene, and MBR-reversing agents increase cellular uptake. These results suggest that $^{99m}Tc$-MIBI can be used for characterizing Pgp expression and developing MDR-reversing agents in vitro.

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