• Tuberculosis and Respiratory Diseases
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• v.66 no.3
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• pp.198-204
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• 2009

Background: First-line drugs, if sensitive, are the most potent drugs in the treatment of multidrug-resistant tuberculosis (MDR-TB). This study examined the frequency and risk factors associated with acquired drug resistance to first-line drugs during a standardized treatment using first-line drugs in patients with MDR-TB. Methods: This study included patients who were diagnosed with MDR-TB at the National Masan Tuberculosis Hospital between January 2004 and May 2008, treated with standardized first-line drugs, and for whom the preand post-treatment results of the drug susceptibility test were available. Their medical records were reviewed retrospectively. Results: Of 41 MDR-TB patients, 14 (34.1%) acquired additional resistance to ethambutol (EMB) or pyrazinamide (PZA). Of 11 patients initially resistant to isoniazid (INH) and rifampicin (RFP), 3 (27.3%) acquired additional resistance to both EMB and PZA, and 3 (27.3%) to PZA. Of 18 patients initially resistant to INH, RFP and EMB, 6 (33.3%) acquired additional resistance to PZA. Of 6 patients initially resistant to INH, RFP and PZA, 2 (33.3%) acquired additional resistance to EMB. Ten of the 41 MDR-TB patients (24.4%) changed from resistant to susceptible. No statistically significant risk factors associated with acquired resistance could be found. Conclusion: First-line drugs should be used cautiously in the treatment of MDR-TB in Korea considering the potential acquisition of drug resistance.

• The Journal of Internal Korean Medicine
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• v.43 no.3
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• pp.460-468
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• 2022

Objective: In this case report, we address the case of a 22-year-old man complaining of generalized tonic-clonic seizures due to drug-resistant epilepsy. Methods: A patient was treated with Korean medicine, including herbal medication, Shihogyeji-tang (SGT), and acupuncture. We evaluated improvements in symptoms using the Korean version of the Epilepsy Self-Efficacy Scale and quality of life. Results: After 37 days of Korean medicine treatment, there were improvements in the patient's quality of life and self-efficacy in seizure control. Conclusions: This case report suggests that SGT and acupuncture might be effective in drug-resistant epilepsy via action on neurons. SGT showed excellent tolerability for drug-resistant epilepsy patients. Our experience provides evidence that SGT and acupunctue may be used as alternative treatment options when antiepileptic drugs do not work in epilepsy patients.

• Journal of Microbiology and Biotechnology
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• v.32 no.6
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• pp.816-823
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• 2022

The rapid spread of superbugs leads to the escalation of infectious diseases, which threatens public health. Endolysins derived from bacteriophages are spotlighted as promising alternative antibiotics against multi-drug resistant bacteria. In this study, we isolated and characterized the novel Salmonella typhimurium phage PBST08. Bioinformatics analysis of the PBST08 genome revealed putative endolysin ST01 with a lysozyme-like domain. Since the lytic activity of the purified ST01 was minor, probably owing to the outer membrane, which blocks accessibility to peptidoglycan, antimicrobial peptide cecropin A (CecA) was fused to the N-terminus of ST01 to disrupt the outer membrane. The resulting CecA::ST01 has been shown to have increased bactericidal activity against gram-negative pathogens including Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, and Enterobacter cloacae and the most affected target was A. baumannii. In the presence of 0.25 µM CecA::ST01, A. baumannii ATCC 17978 strain was completely killed and CCARM 12026 strain was wiped out by 0.5 µM CecA::ST01, which is a clinical isolate of A. baumannii and resistant to multiple drugs including carbapenem. Moreover, the larvae of Galleria mellonella could be rescued up to 58% or 49% by the administration of CecA::ST01 upon infection by A. baumannii 17978 or CCARM 12026 strain. Finally, the antibacterial activity of CecA::ST01 was verified using 31 strains of five gram-negative pathogens by evaluation of minimal inhibitory concentration. Thus, the results indicate that a fusion of antimicrobial peptide to endolysin can enhance antibacterial activity and the spectrum of endolysin where multi-drug resistant gram-negative pathogens can be efficiently controlled.

• Journal of Yeungnam Medical Science
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• v.12 no.1
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• pp.32-47
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• 1995

Glutathione(GSH) has a very important role in detoxification of cells and is closely related to antitumor drug-resistance of cancer cells. In order to evaluate the importance of glutathione metabolism in the drug-resistant cancer cells, the concentration of celluar GSH and activities of ${\gamma}$-glutamylcysteine synthetase(GCS), ${\gamma}$-glutamyl transpeptidase (GGT) and glutathione S-transferases(GST) in the adriamycin, vincristine, or cisplatin resistant L1210 (L1210AdR, L1210VcR, or L1210Cis) sublines were measured. Expression and amplification of GCS, GGT, and GST-${\pi}$ genes were also observed in the parent Ll210 and the drug-resistant Ll210 sublines. The concentration of GSH was increased 5.34 fold in L1210Cis, 2.83 fold in L1210VcR, and 1.78 fold in L1210AdR, compared to L1210. The activities of GCS and GGT were increased in drug-resistant L1210 sublines. The GST activity was increased in L1210VcR and L1210Cis but decreased in L1210AdR compared to Ll210. Expression of GCS, GGT, and GST-${\pi}$ genes were increased in the resistant L1210 sublines compare to the parent L1210 in northern blot analyses. Overexpression of GCS, GGT, and GST-${\pi}$ were observed in the resistant sublines, and the increases of the concentration of glutathione and the activities of GCS and GGT in the resistant sublines may be involved in a part of the drug-resistance in the resistant sublines.

• The Korean Journal of Health Service Management
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• v.8 no.4
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• pp.163-173
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• 2014

This study was performed to investigate the current status of isolation precautions of multidrug resistant organisms(MDROs) in general hospitals with more than 200bed. The questionnaires were mailed from 3rd, April 2013 to 30th, April 2013. Methicillin resistant Staphylococcus aureus:(MRSA), vancomycin resistant Staphylococcus aureus:(VRSA), vancomycin resistant Enterococcus(VRE), multidrug-resistant Acinetobacter baumannii, carbapenem-resistant Enterobacteriaceae multidrug-resistant Pseudomonas aeruginosa were enrolled. MRSA(100.0%) and VRE(98.7%) were isolated respectively. VRE(97.3%) and MRSA(64.0%) were regulated strictly respectively. VRE(91.5%) and VRSA(50.7%) were isolated in a single room respectively. Hospital being located in Seoul(p<0.001), and beds(${\geq}600$)(p=0.008) were different significantly. The isolation space limitation(71.1%) was the highest difficulty. The development of refunding the costs of the extra supplies and other hygienic materials for infection control was discovered as the most urgent strategy.

• Biomolecules & Therapeutics
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• v.31 no.4
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• pp.446-455
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• 2023

The mechanistic functions of 3-deoxysappanchalcone (3-DSC), a chalcone compound known to have many pharmacological effects on lung cancer, have not yet been elucidated. In this study, we identified the comprehensive anti-cancer mechanism of 3-DSC, which targets EGFR and MET kinase in drug-resistant lung cancer cells. 3-DSC directly targets both EGFR and MET, thereby inhibiting the growth of drug-resistant lung cancer cells. Mechanistically, 3-DSC induced cell cycle arrest by modulating cell cycle regulatory proteins, including cyclin B1, cdc2, and p27. In addition, concomitant EGFR downstream signaling proteins such as MET, AKT, and ERK were affected by 3-DSC and contributed to the inhibition of cancer cell growth. Furthermore, our results show that 3-DSC increased redox homeostasis disruption, ER stress, mitochondrial depolarization, and caspase activation in gefitinib-resistant lung cancer cells, thereby abrogating cancer cell growth. 3-DSC induced apoptotic cell death which is regulated by Mcl-1, Bax, Apaf-1, and PARP in gefitinib-resistant lung cancer cells. 3-DSC also initiated the activation of caspases, and the pan-caspase inhibitor, Z-VAD-FMK, abrogated 3-DSC induced-apoptosis in lung cancer cells. These data imply that 3-DSC mainly increased mitochondria-associated intrinsic apoptosis in lung cancer cells to reduce lung cancer cell growth. Overall, 3-DSC inhibited the growth of drug-resistant lung cancer cells by simultaneously targeting EGFR and MET, which exerted anti-cancer effects through cell cycle arrest, mitochondrial homeostasis collapse, and increased ROS generation, eventually triggering anti-cancer mechanisms. 3-DSC could potentially be used as an effective anti-cancer strategy to overcome EGFR and MET target drug-resistant lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.7037-7041
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• 2014

Background: 5-Fluorouracil (5-FU) is the most commonly used drug in colon cancer therapy. However, despite impressive clinical responses initially, development of drug resistance to 5-Fu in human tumor cells is the primary cause of failure of chemotherapy. In this study, we established a 5-Fu-resistant human colon cancer cell line for comparative chemosensitivity studies. Materials and Methods: Real time PCR and Western blotting were used to determine gene expression levels. Cell viability was measured by MTT assay. Glucose uptake was assess using an Amplex Red Glucose/Glucose Oxidase assay kit. Results: We found that 5-Fu resistance was associated with the overexpression of Glut1 in colon cancer cells. 5-Fu treatment at low toxic concentration induced Glut1 expression. At the same time, upregulation of Glut1 was detected in 5-Fu resistant cells when compared with their parental cells. Importantly, inhibition of Glut1 by a specific inhibitor, WZB117, significantly increased the sensitivity of 5-Fu resistant cells to the drug. Conclusions: This study provides novel information for the future development of targeted therapies for the treatment of chemo-resistant colon cancer patients. In particular it demonstrated that Glut1 inhibitors such as WZB117 may be considered an additional treatment options for patients with 5-Fu resistant colon cancers.

• Journal of Microbiology
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• v.45 no.4
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• pp.358-363
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• 2007

Multi-drug resistant Pseudomonas aeruginosa has been implicated in a variety of serious therapeutic problems in clinical environments. Among the 968 P. aeruginosa isolates obtained from two hospitals in Daegu, Korea, we acquired 17 isolates that were resistant to all available tested antimicrobial agents, with the exception of colistin (colistin-only sensitive). We characterized the antimicrobial susceptibilities, $metallo-{\beta}-lactamases$, and epidemiological relatedness among the colistin-only sensitive P. aeruginosa isolates. All colistin-only sensitive isolates were positive in the modified Hodge test and imipenem-EDTA synergy test, thereby indicating the production of $metallo-{\beta}-lactamases$. 11 isolates from the secondary hospital and six isolates from the tertiary teaching hospital harbored $bla_{VIM-2}$ and $bla_{IMP-1}$, respectively. The pulsed-field gel electrophoretic analysis of the SpeI-digested DNA from P. aeruginosa isolates indicated that two different clones of colistin-only sensitive P. aeruginosa originated from each hospital, and had spread within the hospital environment. Overall, colistin-only sensitive P. aeruginosa was detected in Korea for the first time, but no pan-drug resistant bacteria were identified. Nationwide surveillance is required in order to monitor the emergence of colistin-only sensitive or pan-drug resistant bacteria.

• Tuberculosis and Respiratory Diseases
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• v.86 no.3
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• pp.234-244
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• 2023

Background: Effective treatment of fluoroquinolone-resistant multidrug-resistant tuberculosis (FQr-MDR-TB) is difficult because of the limited number of available core anti-TB drugs and high rates of resistance to anti-TB drugs other than FQs. However, few studies have examined anti-TB drugs that are effective in treating patients with FQr-MDR-TB in a real-world setting. Methods: The impact of anti-TB drug use on treatment outcomes in patients with pulmonary FQr-MDR-TB was retrospectively evaluated using a nationwide integrated TB database (Korean Tuberculosis and Post-Tuberculosis). Data from 2011 to 2017 were included. Results: The study population consisted of 1,082 patients with FQr-MDR-TB. The overall treatment outcomes were as follows: treatment success (69.7%), death (13.7%), lost to follow-up or not evaluated (12.8%), and treatment failure (3.9%). On a propensity-score-matched multivariate logistic regression analysis, the use of bedaquiline (BDQ), linezolid (LZD), levofloxacin (LFX), cycloserine (CS), ethambutol (EMB), pyrazinamide, kanamycin (KM), prothionamide (PTO), and para-aminosalicylic acid against susceptible strains increased the treatment success rate (vs. unfavorable outcomes). The use of LFX, CS, EMB, and PTO against susceptible strains decreased the mortality (vs. treatment success). Conclusion: A therapeutic regimen guided by drug-susceptibility testing can improve the treatment of patients with pulmonary FQr-MDR-TB. In addition to core anti-TB drugs, such as BDQ and LZD, treatment of susceptible strains with later-generation FQs and KM may be beneficial for FQr-MDR-TB patients with limited treatment options.

• Clinical and Experimental Pediatrics
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• v.52 no.1
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• pp.61-67
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• 2009

Purpose : The rate of drug-resistant tuberculosis (DR-TB) in children is an indicator of the effectiveness of TB control programs in the community. This study aimed to assess the prevalence of DR-TB in children and evaluate TB management. Methods : Between January 1999 and July 2007, drug susceptibility tests for anti-TB drugs were employed for patients aged less than 19 years with culture-positive TB. Results : A total of 607 cases (16.6%) were resistant to at least one anti-TB drug as follows: isoniazid (INH; 13.8%), rifampin (8.9%), pyrazinamide (4.2%), streptomycin (3.7%), ethambutol (EMB; 5.9%), and para-aminosalicylic acid (PAS; 1.9%). Multidrug-resistant (MDR) TB was found in 276 cases (7.6%); extensive drug resistant (XDR) TB, in 5 cases (0.2%). The rate of resistance to at least one anti-TB drug in children aged >15 years (16.1%) was significantly lower than that in children aged <15 years (20.5%) (P=0.016). The rate of resistance to at least one anti-TB drug and multidrug-resistance in this survey decreased significantly (P<0.001) as compared to the previous survey (1987-1995). The rate of resistance to INH, EMB, and PAS also significantly decreased (P<0.05). Conclusion : The rate of DR-TB in children in Korea has decreased over time; however, it remains higher than that in other countries. MDR-TB and XDR-TB are the emerging problems in Korean children. Therefore, the selection of effective drugs through drug susceptibility tests and evaluating risk factors of resistant TB is essential to successful therapy and a decreased incidence of DR-TB.