• Tuberculosis and Respiratory Diseases
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• v.46 no.5
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• pp.618-627
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• 1999

Background : Rifampicin (RFP) is a key component of the antituberculous short-course chemotherapy. Usually the RFP resistant M.tuberculosis is also resistant to isoniazid (INH), so the RFP resistance is the marker of multi-drug resistant (MDR) tuberculosis. But unusual cases of mono-RFP-resistant tuberculosis have been recently reported with increasing frequency, especially associated with HIV infection in western countries. Therefore, we conducted a retrospective study to investigate the frequency, causes, and the clinical characteristics of mono-RFP-resistant tuberculosis in Korea. Methods : Of the bacteriologically confirmed and susceptibility-proven 699 pulmonary tuberculosis patients (921 isolates) who visited Asan Medical Center from January 1990 to August 1997, eighteen patients with INH-susceptible and RFP-resistant tuberculosis were evaluated. Previous history of tuberculosis, antituberculous drug compliances, associated systemic illness, drug susceptibility patterns, and clinical outcomes were analysed. And rpoB gene sequencing was done in 6 clinical isolates of M. tuberculosis. Results : The mean age of 18 patients was $43{\pm}14$ years, and the sex ratio is 12:6 (M : F). Sixteen (89%) patients had previous history of tuberculosis. None had diagnosed gastrointestinal disorders, and 2 HIV tests that were performed came out negative. Susceptibility tests were done repeatedly in eleven patients, and six (55%) were mono-RFP resistant repeatedly while five (45%) evolved to MDR tuberculosis. Eight (44%) patients were cured, six (33%) failed, three (17%) were lost to follow-up, and the other one is now on treatment. rpoB gene sequencing showed 5 mutations, codon 531 TCG to TIG mutation in 4 isolates and 526 CAC to TAC in 1 isolate. Conclusion : The clinical characteristics of mono-RFP resistant tuberculosis were similar to that of MDR tuberculosis in Korea where the HIV infection rate is lower than western countries. But some patients with mono-RFP-resistant tuberculous could be cured by primary drug regimens including RFP, suggesting that mono-RFP-resistant tuberculous is a different entity from MDR tuberculosis.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.6089-6092
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• 2015

Background: The prevalence of metronidazole-resistant H. pylori is almost 50% in Thailand which severely limits the use of this drug for eradication therapy. The aims of this study were to evaluate the efficacy and safety profiles of 7-day bismuth-based quadruple therapy including metronidazole as an initial treatment for H. pylori infection in a high metronidazole resistance area. Materials and Methods: This study was performed at Thammasat University Hospital and King Chulalongkorn Memorial Hospital during January 2009 to October 2010. Patients with non-ulcer dyspepsia (NUD) with active H. pylori infection were assigned to receive seven days of quadruple therapy (pantoprazole 40 mg bid, bismuth subsalicylate 1,048 mg bid, amoxicillin 1 gm bid and metronidazole 400 mg tid). H. pylori infection was defined as positive H. pylori culture or two positive tests (rapid urease test and histology). Antibiotic susceptibility test for metronidazole by Epsilometer test (E-test) was performed in all positive cultures. At least four weeks after treatment, $^{13}C$ urea breath test ($^{13}C-UBT$) was performed to confirm H. pylori eradication. Results: A total of 114 patients were enrolled in this study, 50 males and 64 females with a mean age of 49.8 years. All 114 patients had a diagnosis of NUD. Overall eradication as confirmed by negative $^{13}C-UBT$ was achieved in 94 out of 114 patients (82.5%). 44 patients had positive cultures and success for E-test. In vitro metronidazole resistance was observed in 22/44 (50%) patients. Eradication rate in patients with metronidazole resistant strains was 16/22 (72.7%) and 20/22 (90.1%) with metronidazole sensitive strains (72.7% vs 90.1%, p-value=0.12; OR=3.75 [95%CI=0.6-31.5]). Minor adverse reactions included nausea, bitter taste, diarrhea and black stools but none of the patients dropped out from the study. Conclusions: Initial treatment with 7-day bismuth-based quadruple therapy including metronidazole, amoxycillin and pantoprazole is highly effective and well tolerated for metronidazole-sensitive H. pylori infections. However, the efficacy markedly decline with metronidazole resistance. Longer duration of this regimen might be required to improve the eradication rate and larger multi-center studies are needed to confirm this hypothesis.

• 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).

• Tuberculosis and Respiratory Diseases
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• v.59 no.3
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• pp.250-256
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• 2005

Background : Fluoroquinolone drugs are an important anti-tuberculous agent for the treatment of multi-drug resistant tuberculosis. However, many drugs belonging to the fluoroquinolones have different cross resistance to each other. Methods : Sixty-three ofloxacin (OFX) resistant and 10 pan-susceptible M. tuberculosis isolates were selected, and compared for their cross resistance using a proportion method on Lowenstein-Jensen media, containing ofloxacin (OFX), ciprofloxacin (CIP), levofloxacin (LVX), moxifloxacin (MXF), gatifloxacin (GAT) and sparfloxacin (SPX), at concentrations ranging from 0.5 to $3{\mu}g/ml$. DNA extracted from the isolates was directly sequenced after amplifying from the gyrA and gyrB genes. Results : The 63 OFX resistant M. tuberculosis isolates showed complete cross resistance to CIP, but only 90.5, 44.4, 36.5 and 46.0% to LVX, MXF, GAT, and to SPX, respectively. Fifty-one of the isolates (81.0%) had point mutations in codons 88, 90, 91 and 94 in gyrA, which are known to be correlated with OFX resistance. The Gly88Ala, Ala90Valand Asp94Ala mutations in gyrA showed a tendency to be susceptible to MXF, GAT and SPX. Only 4 isolates had mutations in the gyrB gene, which did not affect the OFX resistance. Conclusion : About 60% of the OFX resistant M. tuberculosis isolates were susceptible to GAT, SPX and MXF. These fluoroquinolones may be useful in the treatment of TB patients showing OFX resistance.

• Mycobiology
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• v.40 no.1
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• pp.20-26
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• 2012

The complexes of tailor made ligands with life essential metal ions may be an emerging area to answer the problems of multi drug resistance. The coordination complexes of VO(II), Co(II), Ni(II) and Cu(II) with the Schiff bases derived from isatin with 3-chloro-4-floroaniline and 2-pyridinecarboxaldehyde with 4-aminoantipyrine have been synthesized by conventional as well as microwave methods. These compounds have been characterized by elemental analysis, molar conductance, electronic spectra, FT-IR, FAB mass and magnetic susceptibility measurements. FAB mass data show degradation of complexes. Both the ligands behave as bidentate and tridentate coordinating through O and N donor. The complexes exhibit coordination number 4, 5 or 6. The Schiff base and metal complexes show a good activity against the bacteria; $Staphylococcus$ $aureus$, $Escherichia$ $coli$ and $Streptococcus$ $fecalis$ and fungi $Aspergillus$ $niger$, $Trichoderma$ $polysporum$, $Candida$ $albicans$ and $Aspergillus$ $flavus$. The antimicrobial results also indicate that the metal complexes are better antimicrobial agents as compared to the Schiff bases. The minimum inhibitory concentrations of the metal complexes were found in the range 10-40 ${\mu}g/mL$.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3907-3912
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• 2015

Purpose: To investigate the antitumor activity and mechanism of chloroquine (CQ) in combination with cisplatin (DDP) in nude mice xenografted with gastric cancer SGC7901 cells. Materials and Methods: 35 cases of gastric cancer patients with malignant ascites were enrolled and intraperitoneal cisplatin injection was performed. Ascites were collected before and 5 days after perfusion for assessment of autophagy levels in cancer cells. In addition, 24 tumor-bearing mice were randomly divided into control, DDP, CQ and CQ + DDP groups. Results: In 54.3% (19/35) of patients the treatment was therapeutically effective (OR), 5 days after peritoneal chemotherapy, 13 patients had the decreased ascites Beclin-1 mRNA levels. In 16 patients who had NR, only 2 cases had decreased Beclin-1 (P=0.001). Compared with the control group, the xenograft growth in nude mice in the DDP group was low, and the inhibition rate was 47.6%. In combination with chloroquine, the inhibition rate increased to 84.7% (P<0.01). The LC3-II/I ratio, and Beclin1 and MDR1/P-gp expression were decreased, while caspase 3 protein levels increased (P<0.05). Conclusions: Antitumor ability of cisplatin was associated with autophagy activity and chloroquine can enhance chemosensitivity to cisplatin in gastric cancer xenografts nude mice.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1009-1014
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• 2016

It is not clear how gene polymorphisms affecting drugs can contributes totheir efficacy in multiple myeloma (MM). We here aimed to explore associations among gene polymorphisms of tumor necrosis factor alpha (TNFalpha), nitric oxide synthesis 3 (NOS3) and multi-drug resistance 1 (MDR1), clinical parameters, prognosis and survival in MM patients treated with VAD (vincristine-adriamycine-dexamethasone), MP (mephalane-prednisolone), autolougus stem cell transplantation (ASCT), BODEC (bortezomib-dexamethasone-cyclophosphamide) and TD (thalidomide-dexamethasone). We analyzed TNFalpha, NOS 3 and MDR1 in 77 patients with MM and 77 healthy controls. The genotyping was performed with PCR and/or PCR-RFLP. There was no clinically significant difference between MM and control groups when TNFalpha (-238) and (-857) and MDR1 gene polymorphisms were studied. However, the TNFalpha gene polymorphism (-308) GG genotype (p=0.012) and NOS3 (+894) TT genotype (p=0.008) were more common in the MM group compared to healthy controls. NOS3 (VNTR) AA (p=0.007) and NOS3 (+894) GG genotypes (p=0.004) were decreased in the MM group in contrast. In conclusion, the NOS3 (+894) TT and TNFalpha (-308) GG genotypes may have roles in myeloma pathogenesis.

• Journal of Microbiology and Biotechnology
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• v.25 no.8
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• pp.1299-1306
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• 2015

This study aims to investigate the mechanism of action of the cinnamon bark essential oil (CB), when used singly and also in combination with piperacillin, for its antimicrobial and synergistic activity against beta-lactamase TEM-1 plasmid-conferred Escherichia coli J53 R1. Viable count of bacteria for this combination of essential oil and antibiotic showed a complete killing profile at 20 h and further confirmed its synergistic effect by reducing the bacteria cell numbers. Analysis on the stability of treated cultures for cell membrane permeability by CB when tested against sodium dodecyl sulfate revealed that the bacterial cell membrane was disrupted by the essential oil. Scanning electron microscopy observation and bacterial surface charge measurement also revealed that CB causes irreversible membrane damage and reduces the bacterial surface charge. In addition, bioluminescence expression of Escherichia coli [pSB1075] and E. coli [pSB401] by CB showed reduction, indicating the possibility of the presence of quorum sensing (QS) inhibitors. Gas-chromatography and mass spectrometry of the essential oil of Cinnamomum verum showed that trans-cinnamaldehyde (72.81%), benzyl alcohol (12.5%), and eugenol (6.57%) were the major components in the essential oil. From this study, CB has the potential to reverse E. coli J53 R1 resistance to piperacillin through two pathways; modification in the permeability of the outer membrane or bacterial QS inhibition.

• Journal of Microbiology
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• v.41 no.1
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• pp.1-6
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• 2003

The genetic relatedness of multidrug-resistant pneumococcal isolates of serotypes 19F and 23F was investigated. The DNA fragments digested with Sma I were resolved by pulsed-field gel electrophoresis (PFGE). PFGE analysis of 365. pneumoniae isolates showed 13 different patterns. Among 22 isolates of serotype 19F, 9 different PFGE patterns were present and 14 isolates of serotype 23F isolates represented 5 distinct PFGE patterns. Two isolates of serotype 19F and six isolates of serotype 23F shared the same PFGE pattern (Pattern I). Based on the genetic relatedness within the strains (one genetic cluster was defined as having more than 85% homology), we divided the pneumococcal strains into genefic clusters (Ⅰ, II, III, IV, V, and VI). The 22 strains of serotype 19F belonged to five distinct genetic clusters (I, II, III, IV, V and VI) and 14 strains of serotype 23F represented two genetic clusters (I and II ). These results showed that strains of serotype 19F are genetically more diverse than those of serotype 23F, Serotype 19F isolates with PFGE patterns H and I appeared to be less related to those of the remaining PFCE patterns (A to G) (less than 60% genetic relatedness), but those strains were genetically closely related with serotype 23f. These results suggest that the latter isolates originated from horizontal transfer of the capsular type 19F gene locus to 23F pneumococcal genotypes. In conclusion, the multidrug-resistant pneumococcal isolates of serotype 19f and 23F isolated in Korea are the result of the spread of a limited number of resistant clones.

• Journal of the Korean Applied Science and Technology
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• v.35 no.4
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• pp.1386-1392
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• 2018

Cispatin has become one of the most widely used anticancer drugs for decades. One of the drawback of cisplatin (II) complex is that it not only targets cancerous cells but also normal cells causing several serious side effects in patients. We have synthesized Pt(IV) complex that are needed to have the ability to kill target cells selectively in a short time before drug resistance develops. By introducing PDK inhibitor, butyric acid and valproic acid, on Pt complex, two fusion anti-cancer agents 3 and 4 have been synthesized and characterized their structures by nmr and mass spectrometer. MTT assay was performed with $Pt(IV)-Bu_2$ 3 and $Pt(IV)-Val_2$ 4 against MCF-7 cell line. As a result, cisplatin, Pt(IV) complexes 3 and 4 were treated, cell viabilities at $50{\mu}M$ cencentration were decreased to 39%, 54% and 84% respectively.