• Tuberculosis and Respiratory Diseases
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• v.78 no.2
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• pp.78-84
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• 2015

Background: Reports of therapeutic drug monitoring (TDM) for second-line medications to treat multidrug-resistant tuberculosis (MDR-TB) remain limited. Methods: A retrospective cohort from the Virginia state tuberculosis (TB) registry, 2009-2014, was analyzed for TDM usage in MDR-TB. Drug concentrations, measured at time of estimated peak ($C_{max}$), were compared to expected ranges. Results: Of 10 patients with MDR-TB, 8 (80%) had TDM for at least one drug (maximum 6 drugs). Second-line drugs tested were cycloserine in seven patients (mean $C_{2hr}$, $16.6{\pm}10.2{\mu}g/mL$; 4 [57%] below expected range); moxifloxacin in five (mean $C_{2hr}$, $3.2{\pm}1.5{\mu}g/mL$; 1 [20%] below); capreomycin in five (mean $C_{2hr}$, $21.5{\pm}14.0{\mu}g/mL$; 3 [60%] below); para-aminosalicylic acid in five (mean $C_{6hr}$, $65.0{\pm}29.1{\mu}g/mL$; all within or above); linezolid in three (mean $C_{2hr}$, $11.4{\pm}4.1{\mu}g/mL$, 1 [33%] below); amikacin in two (mean $C_{2hr}$, $35.3{\pm}3.7{\mu}g/mL$; 1 [50%] below); ethionamide in one ($C_{2hr}$, $1.49{\mu}g/mL$, within expected). Two patients died: a 38-year-old woman with human immunodeficiency virus/acquired immune deficiency syndrome and TB meningitis without TDM, and a 76-year-old man with fluoroquinolone-resistant (pre-extensively drug-resistant) pulmonary TB and low linezolid and capreomycin concentrations. Conclusion: Individual pharmacokinetic variability was common. A more standardized approach to TDM for MDR-TB may limit over-testing and maximize therapeutic gain.

• Journal of IKEEE
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• v.24 no.4
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• pp.1022-1027
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• 2020

In this paper, SVM-based speaker classification is experimented with GMM-supervector. To create a speaker cluster, conventional speaker change detection is performed with the KL distance using the SNR-based weighting function. SVM-based speaker classification consists of two steps. In the first step, SVM-based classification between UBM and speaker models is performed, speaker information is indexed in each cluster, and then grouped by speaker. In the second step, the SVM-based classification between UBM and speaker models is performed by inputting the speaker cluster group. Linear and RBF are applied as kernel functions for SVM-based classification. As a result, in the first step, the case of applying the linear kernel showed better performance than RBF with 148 speaker clusters, MDR 0, FAR 47.3, and ER 50.7. The second step experiment result also showed the best performance with 109 speaker clusters, MDR 1.3, FAR 28.4, and ER 32.1 when the linear kernel was applied.

• Tuberculosis and Respiratory Diseases
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• v.64 no.3
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• pp.187-193
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• 2008

Background: Multidrug-resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB) are serious threats to worldwide tuberculosis control, but the national burden and the trends of infectious spread are largely unknown. Methods: We retrospectively reviewed the results of drug sensitivity tests and medical records of patients that were diagnosed with culture-confirmed pulmonary tuberculosis and were admitted to the National Masan Tuberculosis Hospital between 2001 and 2005. Results: From 2001 to 2005, the proportion of MDR-TB among new cases was 9.2%, 13.8%, 16.9%, 23% and 27.0% in 2001, 2002, 2003, 2004 and 2005, respectively, and the proportion of MDR-TB among previously treated cases was 58.5%, 60.2%, 62.7%, 61.7% and 71.3% in 2001, 2002, 2003, 2004 and 2005, respectively. A significant increasing trend could be discerned for MDR-TB among both new and previously treated cases (p<0.001, p=0.002 for trend, respectively). The proportion of XDR-TB among new cases was 0%, 2.3%, 3.1%, 2.5% and 6.3% in 2001, 2002, 2003, 2004 and 2005, respectively, and the proportion of XDR-TB among previously treated cases was 9.1%, 15.7%, 17.3%, 19.9% and 19.1% in 2001, 2002, 2003, 2004 and 2005, respectively. A significant increasing trend could be discerned for XDR-TB among both new and previously treated cases (p=0.005, p<0.001 for trend, respectively). Conclusion: Both MDR-B and XDR-TB were gradually increased among both new and previously treated cases. Integrated national surveillance, including the public and private sectors, will be needed to estimate the exact status of antituberculous drug resistance.

• Biomedical Science Letters
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• v.18 no.1
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• pp.79-82
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• 2012

Acinetobacter infections are of great concern in clinical settings because of multi-drug resistance (MDR) and high mortality of the infected patients. The MDR Acinetobacter baumannii has emerged as a significant infectious agent in hospitals worldwide. The purpose of this study was to determine for molecular characterization of MDR A. baumannii clinical isolates obtained from the Wonju Christian Hospital in Gangwon province of Korea. A total of seventy nonduplicate A. baumannii isolates were collected from the Wonju Christian Hospital in Korea from March to April in 2011. All of the MDR A. baumannii isolates were encoded by $bla_{OXA-23-like}$ gene and all isolates with the $bla_{OXA-23-like}$ gene had the upstream element ISAba1 to promote increased gene expression and subsequent resistance to carbapenem. 16S rRNA methylase gene (armA) was detected in 44 clinical isolates which were resistant to amikacin, and phosphotransferase genes encoding aac(3)-Ia and aac(6')-Ib were the most prevalent. A combination of 16S rRNA methylase and aminoglycoside-modifying enzyme genes (armA, aac(3)-Ia, aac(6')-Ib, and aph(3')-Ia) were found in 31 isolates. The sequencing results for the quinolone resistance-determining region (QRDR) of gyrA and parC revealed the presence of Ser (TCA) 83 Leu (TTA) and Ser (TCG) 80 Leu (TTG) substitutions in the respective enzymes for all MDR. Molecular typing for MDR A. baumannii could be helpful in confirming the identification of a common source or cross-contamination. This is an important step in enabling epidemiological tracing of these strains.

• Archives of Pharmacal Research
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• v.29 no.9
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• pp.757-761
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• 2006

Six protoberberine alkaloids were isolated from the chloroform layer of the rhizome of Coptis japonica Makino (Ranunculaceae). The structures of the isolated compounds were determined to be 6-([1,3]dioxolo[4,5-g]isoquinoline-5-carbonyl)-2,3-dimethoxy-benzoic acid methyl ester (1), oxyberberine (2), 8-oxo-epiberberine (3), 8-oxocoptisine (4), berberine (5) and palmatine (6) by physicochemical and spectroscopic methods. The compound 3 (8-oxo-epiberberine) was first isolated from natural sources. The compounds were tested for cytotoxicity against five tumor cell lines in vitro by SRB method, and also tested for the MDR reversal activities. Compound 4 was of significant P-gp MDR inhibition activity with ED50 value $0.018\;{\mu}g/mL$ in MES-SA/DX5 cell and $0.0005\;{\mu}g/mL$ in HCT15 cell, respectively.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10597-10601
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• 2015

Up-regulation of multidrug resistance-associated protein 1 (MRP1) is regarded as one of the main causes for multidrug resistance (MDR) of tumor cells, leading to failure of chemotherapy-based treatment for a multitude of cancers. However, whether silencing the overexpressed MRP1 is sufficient to reverse MDR has yet to be validated. This study demonstrated that RNAi-based knockdown of MRP1 reversed the increased efflux ability and MDR efficiently. Two different short haipin RNAs (shRNAs) targeting MRP1 were designed and inserted into pSilence-2.1-neo. The shRNA recombinant plasmids were transfected into cis-dichlorodiamineplatinum-resistant A549 lung (A549/DDP) cells, and then shRNA expressing cell clones were collected and maintained. Real time PCR and immunofluorescence staining for MRP1 revealed a high silent efficiency of these two shRNAs. Functionally, shRNA-expressing cells showed increased rhodamine 123 retention in A549/DDP cells, indicating reduced efflux ability of tumor cells in the absence of MRP1. Consistently, MRP1-silent cells exhibited decreased resistance to 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and DDP, suggesting reversal of MDR in these tumor cells. Specifically, MRP1 knockdown increased the DDP-induced apoptosis of A549/DDP cells by increased trapping of their cell cycling in the G2 stage. Taken together, this study demonstrated that RNAi-based silencing of MRP1 is sufficient to reverse MDR in tumor cells, shedding light on possible novel clinical treatment of cancers.

• Journal of Microbiology and Biotechnology
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• v.29 no.9
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• pp.1460-1469
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• 2019

The extensive distribution of multidrug-resistant (MDR) methicillin-resistant Staphylococcus aureus (MRSA) poses a threat to healthcare worldwide. This study aimed to investigate the MDR and molecular patterns of MRSA isolates in children admitted to the two biggest tertiary care pediatric hospitals in northern and southern Vietnam. A total of 168 MRSA strains were collected to determine antibiotic susceptibility by minimum inhibitory concentration tests. Antibiotic-resistant genes, pulsed-field gel electrophoresis, staphylococcal cassette chromosome mec (SCCmec) typing, and multilocus sequence typing were used for the molecular characterization of MRSA. Among the total strains, the MDR rate (51.8%) was significantly higher in the northern hospital than in the southern hospital (73% vs. 39%, p < 0.0001). The MDR-MRSA with the highest rates were "ciprofloxacin-erythromycin-gentamicintetracyclines" (35.6%), followed by "erythromycin-tetracycline-chloramphenicol" (24.1%), and "ciprofloxacin-erythromycin-gentamicin" (19.5%), showing an accumulative total of 79.3%. The most susceptible antibiotics were rifampicin (100%) and vancomycin (100%), followed by doxycycline (94.0%), meropenem (78.0%), and cefotaxime (75.0%). The SCCmecII strains showed greater resistance to gentamicin, ciprofloxacin, tetracycline, meropenem and cephalosporins compared with the other strains. The SCCmecII strains exhibited the highest rate in the tested genes (aacA/aphD: 55.2%, ermA/B/C: 89.7%, and tetK/M: 82.8%). ST5-SCCmecII was the predominant clone in the northern hospital, whereas SCCmecIVa was more pronounced in the southern hospital. In conclusion, our results raised concerns about the predominant MDR-MRSA strains in the pediatric hospitals in Vietnam. The north-south difference in the antibiotic resistance patterns and genetic structure of MRSA suggests different MRSA origins and various uses of antimicrobial agents between the two regions.

• Journal of Microbiology and Biotechnology
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• v.33 no.9
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• pp.1179-1188
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• 2023

Escherichia coli, particularly multidrug-resistant (MDR) strains, is a serious cause of healthcare-associated infections. Development of novel antimicrobial agents or restoration of drug efficiency is required to treat MDR bacteria, and the use of natural products to solve this problem is promising. We investigated the antimicrobial activity of dried green coffee (DGC) beans, coffee pulp (CP), and arabica leaf (AL) crude extracts against 28 isolated MDR E. coli strains and restoration of ampicillin (AMP) efficiency with a combination test. DGC, CP, and AL extracts were effective against all 28 strains, with a minimum inhibitory concentration (MIC) of 12.5-50 mg/ml and minimum bactericidal concentration of 25-100 mg/ml. The CP-AMP combination was more effective than CP or AMP alone, with a fractional inhibitory concentration index value of 0.01. In the combination, the MIC of CP was 0.2 mg/ml (compared to 25 mg/ml of CP alone) and that of AMP was 0.1 mg/ml (compared to 50 mg/ml of AMP alone), or a 125-fold and 500-fold reduction, respectively, against 13-drug resistant MDR E. coli strains. Time-kill kinetics showed that the bactericidal effect of the CP-AMP combination occurred within 3 h through disruption of membrane permeability and biofilm eradication, as verified by scanning electron microscopy. This is the first report indicating that CP-AMP combination therapy could be employed to treat MDR E. coli by repurposing AMP.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.2083-2087
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• 2016

A new compound namely (13-(3,3-dihydroxypropyl)-1,6-dihydroxy-3,4-dihydro-1H-isochromen-8(5H)-one (1) was isolated from an ethyl acetate extract of the borne fungi Screlotium rolfsii. Its chemical structure was elucidated by spectroscopic analysis. Screlotiumol 1 were evaluated for their effects on the reversion of multidrug resistant (MDR) mediated by P-glycoprotein (P-gp) of the soil borne fungi. The multidrug resistant P-glycoprotein is a target for chemotherapeutic drugs in cancer cells. In the present study rhodamine-123 exclusion screening test on human mdr1 gene transfected mouse gene transfected L5178 and L5178Y mouse T-cell lymphoma which showed excellent MDR reversing effect in a dose dependent manner against mouse T-lymphoma cell line. Moreover, molecular docking studies of compound-1 also showed better results as compared with the standard. Therefore the preliminary results obtained from this study suggest that screlotiumol 1 could be used as a potential agent for the treatment of cancer.

• Tuberculosis and Respiratory Diseases
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• v.43 no.6
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• pp.862-870
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• 1996

Background : Multidrug-resistant tuberculosis(MDR-Tb) has been increased not only in Asia but also in Western society, which may cause public health problems and reduce the efficacy of treatment of tuberculosis. In Western society HIV infection is believed to do a central role in increasing incidence of MDR tuberculosis, but MDR-Tb in Korea may be somewhat different about clinical features, underlying disorders, and prognosis. Goble et al reponed that overall treatment failure rate in MDR-Tb including resistance to isoniazid(INH) and rifampin (RFP) was 44 %. The aim of this study is to find the treatment result in Korea and the factors determining the prognosis. Methods: A retrospective study of pulmonary tuberculosis cultured M. tuberculosis from sputum or bronchial washing fluid between 1986 through 1992 was conducted in the Seoul Paik Hospital, Inje University. We reviewed clinical courses of 141 patients, who had a tuberculosis with resistance to 2 or more drugs including isoniazid(INH) and rifampin(RFP). One hundred and 4 patients of 141 patients had completed treatment and followed up for more than one year. Results: Of 104 (mean age $43.6{\pm}16.7$, M: F=63 : 41) patients with sufficient follow-up data, 73(84.6%) patients responded which is defined as negative Sputum cultures for at least 3 consecutive months. Seven patients(6.7%) had a failure in negative conversion and 9(8.7%) of the patients who initially responded relapsed. Overall treatment failure rate was 15.4%, Patients who were treated for less than 12 months had a higher relapse rate(12.3%) than 18 months(4.9%). And there was a statistically significant correlation between the relapse rate and the number of drugs to which isolates wera resistant(p<0.05). Conclusion : The treatment failure rate of MDR-Tb in Korea was lower than previous studies in western Country and the major determining factor of prognosis was the number of resistant drugs to M. tuberculosis at drug sensitivity test. For reducing the relapse rate, we recommend more than 12 months of treatment for MDR tuberculosis.