• Title/Summary/Keyword: Drug Susceptibility

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Biomarkers and Surrogate Endpoints for Development of New Drug on Pulmonary Disease (폐질환 치료제의 효율적인 신약개발을 위한 생체표지자 및 대리결과 변수)

  • Seo, Jeong-Won;Lee, Byung-Yo;Chae, Jung-Woo;Son, Chu-Young;Kang, Won-Ku;Chae, Han-Jung;Kwon, Kwang-Il
    • YAKHAK HOEJI
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    • v.54 no.2
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    • pp.75-90
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    • 2010
  • Biomarkers are likely to be important in the study of various pulmonary diseases for many reasons. Research efforts in developing biomarkers and surrogate endpoints of lung diseases have resulted in the identification of new risk factors and novel drug targets, as well as the establishment of treatment guidelines. Government agencies, academic research institutions, diagnostic industries, and pharmaceutical companies all recognize the importance of biomarkers in new drug development and advancing therapies to improve public health. In drug development, biomarkers are used to evaluate early signals of efficacy and safety, to select dose, and to identify the target population. Identification of suitable end points not only would help investigators design appropriate clinical trials but would assist clinicians in caring for this patient population. Though the area of pulmonology has received much attention in the past decades, it still lags behind with regard to the development of biomarkers, particularly those of health effects and susceptibility. This review critically summarized several biomarker researches such as Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) study with objectives of identifying the parameters that predict disease progression of COPD, as well as biomarkers that may serve as surrogate end-points.

Antimicrobial Resistance Profile of Acinetobacter spp. Isolates from Retail Meat Samples under Campylobacter-Selective Conditions

  • Cha, Min-Hyeok;Kim, Sun Hee;Kim, Seokhwan;Lee, Woojung;Kwak, Hyo-Sun;Chi, Young-Min;Woo, Gun-Jo
    • Journal of Microbiology and Biotechnology
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    • v.31 no.5
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    • pp.733-739
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    • 2021
  • Acinetobacter strains are widely present in the environment. Some antimicrobial-resistant strains of this genus have been implicated in infections acquired in hospitals. Genetic similarities have been reported between Acinetobacter strains in nosocomial infections and those isolated from foods. However, the antimicrobial resistance of Acinetobacter strains in foods, such as meat, remains unclear. This study initially aimed to isolate Campylobacter strains; instead, strains of the genus Acinetobacter were isolated from meat products, and their antimicrobial resistance was investigated. In total, 58 Acinetobacter strains were isolated from 381 meat samples. Of these, 32 strains (38.6%) were from beef, 22 (26.5%) from pork, and 4 (4.8%) from duck meat. Antimicrobial susceptibility tests revealed that 12 strains were resistant to more than one antimicrobial agent, whereas two strains were multidrug-resistant; both strains were resistant to colistin. Cephalosporin antimicrobials showed high minimal inhibitory concentration against Acinetobacter strains. Resfinder analysis showed that one colistin-resistant strain carried mcr-4.3; this plasmid type was not confirmed, even when analyzed with PlasmidFinder. Analysis of the contig harboring mcr-4.3 using BLAST confirmed that this contig was related to mcr-4.3 of Acinetobacter baumannii. The increase in antimicrobial resistance in food production environments increases the resistance rate of Acinetobacter strains present in meat, inhibits the isolation of Campylobacter strains, and acts as a medium for the transmission of antimicrobial resistance in the environment. Therefore, further investigations are warranted to prevent the spread of antimicrobial resistance in food products.

Detection of Point Mutations in the rpoB Gene Related to Drug Susceptibility in Mycobacterium Tuberculosis using an Oligonucleotide Chip (올리고뉴클레오티드 칩(Oligonucleotide Chip)을 이용한 항결핵제 감수성과 관련된 Mycobacterium tuberculosis rpoB 유전자의 점돌연변이 판별 방법)

  • Kim, Hyun-Jung;Kim, Seong-Keun;Shim, Tae-Sun;Park, Yong-Doo;Park, Mi-Sun
    • Tuberculosis and Respiratory Diseases
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    • v.50 no.1
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    • pp.29-41
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    • 2001
  • Background : The appearance of multiple-drug-resistant Mycobacterium tuberculosis strains has been seriously compromising successful control of tuberculosis. Rifampin-resistance, caused by mutations in the rpoB gene, can be indicative of multiple-drug-resistance, and its detection is of great importance. The present study aimed to develop an oligonucleotide chip for accurate and convenient screening of drug-resistance. Methods : In order to detect point mutations in the rpoB gene, an oligonucleotide chip was prepared by immobilizing specific probe DNA to a microscopic slide glass by a chemical reaction. The probe DNA that was selected from the 81 bp core region of the rpoB gene was designed to have mutation sites at the center. A total of 17 mutant probes related to rifampin-resistance including 8 rifabutin-sensitive mutant probes were used in this study. For accurate determination, wild type probes were prepared for each mutation position with an equal length, which enabled a direct comparison of the hybridization intensities between the mutant and wild type. Results : Mycobacterial genomic DNA from clinical samples was tested with the oligonucleotide chip and the results were compared with those of the drug-susceptibility test in addition to sequencing and INNO-LiPA Rif. TB kit test in some cases. Out of 15 samples, the oligonucleotide chip results of 13 samples showed good agreement with the rifabutin-sensitivity results. The two samples with conflicting result also showed a discrepancy between the other tests, suggesting such possibilities as existence of mixed strains and difference in drug-sensitivity. Further verification of these samples in addition to more case studies are required before the final evaluation of the oligonucleotide chip can be made. Conlcusion : An oligonucleotide chip was developed for the detection of rpoB gene mutations related to drugsusceptibility. The results to date show the potential for using the oligonucleotide chip for accurate and convenient screening of drug-resistance to provide useful information in antituberculosis drug therapy.

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Drug Resistance and R Plasmid of Enterococcus Isolated from Patients (환자(患者)에서 분리(分離)한 Enterococcus의 약제내성(藥劑耐性)과 R Plasmid)

  • Lee, Hern-Ku;Ha, Tai-You
    • The Journal of the Korean Society for Microbiology
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    • v.13 no.1
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    • pp.7-16
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    • 1978
  • One hundred and three clinical isolates of enterococci were examined for susceptibility to 8 antibiotics, and transferability and transfer frequency of R plasmid. Ampicillin was the most active, followed in decreasing order by rifampin, amikacin and chloramphenicol, and tetracycline. High-level resistance(${\geq}2,000{\mu}g/ml$) to kanamycin, streptomycin, and gentamicin, known as the most active of the aminoglycosides to enterococcus, was present in 26.2%, 21.4%, and 18.3% of the isolates, respectively. In the drug susceptibility of the species, S. zymogenes was the most resistant and S. durans was the most sensitive to tested antibiotics. We could observed the transferability of enterococcal R plasmid in mixed culture: among the 28 strains which showed multiple drug resistance, 17 strains transferred all or part of their resistance with $2{\times}10^{-4}-2{\times}10^{-6}%$ of transfer frequency to a plasmid-free recipient, S. faecalis strain JH 2-2.

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Antmicrobial Drug Susceptibility of Pathogenic Bacteria Isolated from Animals in Korea (동물유래(動物由來) 병원세균(病源細菌)의 각종(各種) 항생물질(抗生物質)에 대한 감수성조사(感受性調査))

  • Kim, Bong Hwan;Rhee, Jae Chin;Kim, Ki Seuk;Han, Tae Woo
    • Korean Journal of Veterinary Research
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    • v.20 no.2
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    • pp.85-92
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    • 1980
  • The antimicrobial drug susceptibility of 439 isolates of animal pathogens recovered from various clinical cases during 1978-79 has been investigated by the use of disk diffusion technique. The majority of 308 strains of Eschericihia coli were highly resistant to bacitracin, erythromycin, penicillin, streptomycin and tetracyclinon while only 0.3 per cent of them were resistant to gentamicin and 3.2 per cent to colistin. The percentages of strains resistant to ampicillin, carbenicillin, cephalothin, chloramphenicol and neomycin were 30.5%, 24.7%, 11:4%, 28.2% and 26.2% and repectively. However, none of E. coli cultures of ovine origin were resistant to ampicillin, carbenicillin, chloramphenicol, colistin, gentamicin, kanamycin, and neomycin. A total of 39 patterns of multipe drug1 resistance of 308 strains E. coli against 9 drugs in general use such as ampicillin, cephalothin, chloramphenicol, colistin, gentamicin, kanamycin, neomycin, streptomycin and tetracycline were observed and the most common multiple resistance patterns were SM, TC pattern (20.5%) and AM, CP, KM, NM, SM, TC pattern (9.7%). None of the 43 cultures of salmonella organism from pigs and chickens were resistant to ampicillin, carbenicillin, cephalothin, colistin, gentamicin and kanamycin; and the majority of the cultures were susceptible to chloramphenicol (90.0%), neomycin (97.7%) and tetracycline (93.0%). All the cultures were found to be resistant to bacitracin and penicillin and the rate of resistant strains to erythromycin and s treptomycin being 79.1% and 41.9% respectively. It was found that the majority of 63 cultures of staphylococcal isolates were resistant to lincomycin, penicillin, streptomycin and tetracycline. The percentages of 63 staphylococcal isolates susceptible to gentamicin, nitrofurantoin, cephalothin, ampicillin, methicillin, bacitracin and chloramphenicol were 98.4%, 98.4%, 95.2%, 93.7%, 93.7%, 92.1% and 92.1% respectively. The 25 cultures of streptococcal isolates were resistant in order of prevalence to streptomycin(88.0%), kanamycin(68.0%), gentamicin (44.0%), tetracycline (44.0%) and methicillin (40.0%) wihle the majority of them were sensitive to ampicillin, bacitracin, chloramphenicol and penicillin.

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A Nudix Hydrolase Protein, Ysa1, Regulates Oxidative Stress Response and Antifungal Drug Susceptibility in Cryptococcus neoformans

  • Lee, Kyung-Tae;Kwon, Hyojeong;Lee, Dohyun;Bahn, Yong-Sun
    • Mycobiology
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    • v.42 no.1
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    • pp.52-58
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    • 2014
  • A nucleoside diphosphate-linked moiety X (Nudix) hydrolase-like gene, YSA1, has been identified as one of the gromwell plant extract-responsive genes in Cryptococcus neoformans. Ysa1 is known to control intracellular concentrations of ADP-ribose or O-acetyl-ADP-ribose, and has diverse biological functions, including the response to oxidative stress in the ascomycete yeast, Saccharomyces cerevisiae. In this study, we characterized the role of YSA1 in the stress response and adaptation of the basidiomycete yeast, C. neoformans. We constructed three independent deletion mutants for YSA1, and analyzed their mutant phenotypes. We found that ysa1 mutants did not show increased sensitivity to reactive oxygen species-producing oxidative damage agents, such as hydrogen peroxide and menadione, but exhibited increased sensitivity to diamide, which is a thiol-specific oxidant. Ysa1 was dispensable for the response to most environmental stresses, such as genotoxic, osmotic, and endoplasmic reticulum stress. In conclusion, modulation of YSA1 may regulate the cellular response and adaptation of C. neoformans to certain oxidative stresses and contribute to the evolution of antifungal drug resistance.

Identification and Antimicrobial Susceptibility of Microorganisms Isolated from Bovine Mastitic Milk (젖소의 유방염 원인균 분리 및 약제 감수성 검사)

  • Kang, Hee-Jung;Kim, Ik-Chun;Kim, Jin-Hoe;Son, Won-Geun;Lee, Du-Sik
    • Korean Journal of Veterinary Research
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    • v.41 no.4
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    • pp.511-521
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    • 2001
  • Microorganisms were isolated and identified from bovine 296 quarters which showed positive reaction by California Mastitis Test (CMT) in 40 farms of Jeju from September 1999 to June 2000. The organisms associated with the mastitis of bovine were 11 different bacterial species in this study. Which of them, Staphylococcus aureus was the most predominant species as 152 (51.4%) isolates. Other identified species included 49 (16.5%) coliform, 47 (15.8%) Streptococcus dysgalactiae, 15 (5.1%) Bacillus spp., 8 (2.7%) Staphylococcus epidermidis, 6 (2.1%) Streptococcus agalactiae, 5 (1.7%) Enterococcus faecalis, 5 (1.7%) Corynebacterium spp., 3 (1.0%) Streptococcus uberis, 1 (0.3%) Pseudomonas aeruginosa and 1 (0.3%) Pasteurella haemolytica. Almost of all the islolated beacterial species showed high sensitivity against kanamycin (98.6%), cephalothin (98.0%), streptomycin (94.9%), gentamicin (94.6%), ampicillin (92.2%) and polymyxin B (90.2%). On the contrary, they showed resistance against penicillin (47.0%), tetracycline (37.2%), cefazolin (26.0%), bacitracin (22.6%) and erythromycin (19.9%). Eighty-one isolates were not resistant to any antibiotics and 215 drug resistant isolates showed 89 different drug resistance patterns from single to nine multiple antibiotics resistance patterns.

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Combination of Curcumin and Paclitaxel-loaded Solid Lipid Nanoparticles to Overcome Multidrug Resistance

  • Li, Rihua;Xu, Wenting;Eun, Jae-Soon;Lee, Mi-Kyung
    • Journal of Pharmaceutical Investigation
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    • v.41 no.6
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    • pp.381-386
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    • 2011
  • Multi-drug resistance (MDR) has been known as a major hurdle in cancer chemotherapy. One of the most clinically significant causes of MDR was the efflux of anticancer agents mediated by p-glycoprotein (p-gp) over-expressed in MDR cancer cells. To overcome MDR, there have been several strategies such as co-administration with p-gp inhibitors and encapsulation of anticancer drugs into drug delivery systems. In the present study, curcumin was evaluated for its potential as p-gp inhibitor and MDR reversal activity when combined with paclitaxel incorporated into lipid nanoparticles (PTX/LN). Western blot assay showed curcumin did not modulate the level of p-gp expression in MCF-7/ADR which is a MDR variant of human breast cancer cell line, MCF-7, and over-expresses p-gp. However, curcumin inhibited p-gp-mediated efflux of calcein in a dose-dependent manner even though it showed lower activity compared to verapamil, a well-known p-gp inhibitor. Incorporation of paclitaxel into lipid nanoparticles partially recovered the anticancer activity of paclitaxel in MCF-7/ADR. The combined use of curcumin and PTX/LN exhibited further full reversal of MDR, suggesting susceptibility of PTX/LN to the efflux system. In conclusion, combined approach of using p-gp inhibitors and incorporation of the anticancer agents into nano-delivery systems would be an efficient strategy to overcome MDR.

A Standardization Study of Children's Color Trails Test(CCTT) (아동 색 선로 검사의 표준화 연구)

  • Koo, Hoon-Jung;Shin, Min-Sup
    • Journal of the Korean Academy of Child and Adolescent Psychiatry
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    • v.19 no.1
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    • pp.28-37
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    • 2008
  • Objectives : This study was conducted in order to examine the reliability and validity of the Children's Color Trails Test (CCTT). The objective of the study was also to provide the Korean normative data for the CCTT. Methods : Normative samples consisted of 766 children and adolescents living in Seoul and aged from 5 to 15 years. Eighty children who were diagnosed with ADHD, based on the DSM-IV criterion, were recruited from Seoul National University Children's Hospital. Among them, 46 ADHD children were receiving medication, while 34 children were drug-free. Results : The scores of the CCTT were significantly correlated with those of the Stroop test. Three factors were extracted through factor analysis-visual tracking and cognitive flexibility, distractibility and susceptibility to interference, and simple attention and impulsivity. The completion time of the CCTT for all children tended to decrease as age increased. There were significant differences in the CCTT scores between the ADHD group receiving medication, the ADHD-drug free group and the normal groups. The CCTT also showed sound test-retest reliability. These results confirmed the reliability and validity of the CCTT. Finally, we provided the Korean normative data for the CCTT. Conclusion : These results suggest that the CCTT is a reliable and valid test, which can be used to assess frontal function related to child psychiatric disorders in Korean children.

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Bioserotype and drug resistance of Salmonella spp isolated from feces in zoo animals (동물원(動物園)의 야생동물(野生動物) 분변(糞便)에서 분리(分離)한 살모넬라균의 생물형(生物型), 혈청형(血淸型) 및 약제내성(藥劑耐性))

  • Youn, En-sun;Park, Seog-gee;Oh, Young-hee;Kim, Tae-jong
    • Korean Journal of Veterinary Research
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    • v.34 no.2
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    • pp.267-273
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    • 1994
  • Feces samples, obtained from zoo animals around Seoul, were examined for the isolation of Salmonella species, bioserotype and drug resistance for the prevention and treatment of salmonellosis, Salmonella spp were isolated 19(4.7%) from 408 samples of zoo animals. The subspecies in 19 Salmonella were all subspecies 1. The serological identification of Salmonella isolated were 31.6% in Sal typhimurium, 26.3% in Sal hadar, 21.1% in Sal muenchen, 15.8% in Sal enteritidis and 5.3% in Sal ayinde. The antibiotic resistance of Salmonella isolated were 13(68.4%) strains. The multiple resistant patterns of antibiotics in Salmonella were 2 drugs- and 3 drugs-resistance 30.8% respectively. The transferred rate of resistance to recipients(E coli ML 1410 $NA^r$) in Salmonella was 38.5%.

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