• Title/Summary/Keyword: Troleandomycin

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Reaction Mechanism of Troleandomycin on the Activity of Human Liver Microsomal Cytochrome P450 3A4 (인체 간 조직의 Cytochrome P450 3A4의 활성에 대한 Troleandomycin의 작용기전)

  • 김복량;오현숙;김혜정
    • Toxicological Research
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    • v.11 no.2
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    • pp.329-335
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    • 1995
  • Incubation of aflatoxin $B_1$ $(AFB_1)$ with microsomes isolated from human liver number 110 yielded two metabolite peaks which were aflatoxin $Q_1$ $(AFQ_1)$ and $(AFB_1)$-exo-8, 9-epoxide (exo-epoxide) in high performance liquid chromatography. Production ratio of $AFQ_1$ to exo-epoxide was 2.43$\pm $0.04. Metabolism of $(AFB_1)$ to $(AFQ_1)$ and exo-epoxide was inhibited by troleandomycin in a same degree although troleandomycin was not activated as a mechanism-based inhibitor. The inhibitory effect was dependent upon either the incubation time with $(AFB_1)$ or the preincubation time before the addition of $(AFB_1)$. Incubation of troleandomycin and NADPH by the microsomes resulted in the formation of a cytochrome P 450 (P450)-metabollc intermediate (MI) complex and the level was approximately 80% of total P450 3A4 in the microsomes. This figure was similar to that of the inhibitory effect of troleandomycin on $AFB_1$ metabolism. Glutathione which was reported that it prevented the formation of MI complex in rat liver microsomes did not inhibit the formation of MI complex in human liver microsomes. These results suggested that the inhibitory effect of troleandomycin on $AFB_1$ metabolism is due to the formation of MI complex with P450 3A4. And the reaction mechanism of troleandomycin by human liver microsomes might be dlfferent from that one by rat liver microsomes.

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Effects of Several Inhibitors of Human Liver Microsomal Cytochrome P450 3A4 on Catalytic Activities of the Enzyme (인체 간 조직의 cytochrome P450 3A4의 활성에 대한 몇가지 억제제의 영향)

  • 오현숙;이갑상;김복량
    • Toxicological Research
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    • v.11 no.1
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    • pp.23-29
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    • 1995
  • Microsomes from human liver sample HL 110 oxidized aflatoxin $B_1$ $(AFB_1)$ to $AFB_1$ exo-8, 9-epoxide which was detected as a glutathione (GSH) conjugate with excess GSH S-transferase and to aflatoxin $Q_1$ ($AFB_1$; 3$\alpha$-hydroxyafiatoxin $B_1$), and testosterone to 6$\beta$-hydroxytestosterone. Anti-P450 3A4 nearly completely inhibited all of the reactions. Some fiavonoids inhibited all of the reactions. While other fiayonolds stimulated 8, 9-epoxidation and inhibited 3$\alpha$-hydroxylation. Gestodene inhibited all of the reactions when gestodene was metabolized by human liver microsomal P450 3A4 prior to adding substrate. But, ges-todene was added in the enzyme mixtures in the presence of $AFB_1$, it could not inhibit 8, 9-epoxidation of $AFB_1$. Nifedipine and troleandomycin inhibited both of the reactions of $AFB_1$ but only 3$\alpha$-hydroxylation was inhibited by the oxidation product of nifedipine. Although, troleandomycin was known as a mechanism-based inhibitor, the chemical did not show any detectable inhibitory effect on 6$\beta$-hydroxylation of testosterone. The results suggest that there are several different substrate-binding sites on P450 3A4.

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Characterization of Pyribenzoxim Metabolizing Enzymes in Rat Liver Microsomes

  • Liu Kwang-Hyeon;Moon Joon-Kwan;Seo Jong-Su;Park Byeoung-Soo;Koo Suk-Jin;Lee Hye-Suk;Kim Jeong-Han
    • Toxicological Research
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    • v.22 no.1
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    • pp.1-8
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    • 2006
  • The primary metabolism of pyribenzoxim was studied in rat liver microsomes in order to identify the cytochrome P450 (CYP) isoform(s) and esterases involved in the metabolism of pyribenzoxim. Chemical inhibition using CYP isoform-selective inhibitors such as ${\alpha}$-naphthoflavone, tolbutamide, quinine, chlorzoxazone, troleandomycin, and undecynoic acid indicated that CYP1A and CYP2D are responsible for the oxidative metabolism of pyribenzoxim. And inhibitory studies using eserine, bis-nitrophenol phosphate, dibucaine, and mercuric chloride indicated pyribenzoxim hydrolysis involved in microsomal carboxylesterases containing an SH group (cysteine) at the active center.

Studies on the Antimicrobial Susceptibility of Enterococci isolated at Doctorless areas and Seoul National University Hospital (일부 무의촌지역과 병원에서 분리한 Enterococci의 항균제 감수성에 관한 연구)

  • Kim, Ik-Sang;Shin, Hee-Sup;Rhee, Kwang-Ho;Chang, Woo-Hyun;Lim, Jung-Kyoo
    • The Journal of the Korean Society for Microbiology
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    • v.13 no.1
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    • pp.63-73
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    • 1978
  • 28 strains of Enterococci isolated at doctorless areas in Korea from Oct. 1976 through Mar. 1977 and 30 strains of Enterococci isolated at Seoul National University Hospital from Sep. 1976 through Dec. 1976 were examined for susceptibilities to 14 antimicrobial agents by agar dilution method. The susceptibilities of two groups to each antimicrobial agent were compared and incidence of resistant strains in each antimicrobial agent, incidence of multiply resistant strains and correlations in the antimicrobial susceptibility of 58 strains of Enterococci among 14 antimicrobial agents were analyzed. 1. With Tetracycline, Oxytetracline, Doxycycline, Minocycline and Erythromycin, the mean MIC's of Enterococci isolated at Seoul National University Hospital were 1.9-2.5 times higher than those of Enterococci isolated at doctorless areas, though there were no statistical significance. 2. Frequency of resistant strains in Enterococci isolated at Seoul National University Hospital was the highest with Cephalexin(100%), Gentamicin(100%), and Streptomycin(100%), followed by Kanamycin(93.3%), Carbenicillin(90%), Tetracycline(26.7%), Oxytetracycline(26.7%), Doxycycline(26.7%), Minocycline(20%), Erythromycin(10%), Troleandomycin(10%), Penicillin(6.7%), Cotrimoxazole(6.7%) and Ampicillin(0%). 3. Frequency of resistant strains in Enterococci isolated at doctorless areas was the highest with Kanamycin(100%) and Streptomycin(100%), followed by Cephalexin(96.4%), Gentamicin(96.4%), Carbenicillin(92.9%), Tetracycline(10.7%), Oxytetracycline(10.7%), Doxycycline(10.7%), Minocycline(10.7%), Cotrimoxazole(10.7%), Penicillin(3.6%), Ampicillin(0%), Erythromycin(0%), and Troeandomycin(0%). 4. In study with Penicillin, Ampicillin, Tetracycline, Cotrimoxazole, Erythromycin and Troleandomycin, there were no multiply resistant strains in Enterococci isolated at doctorless areas, while 4 strains of Enterococci isolated at Seoul National University Hospital showed multiple resistance. 5. There were high correlation in susceptibility of 58 strains of Enterococci among Tetracycline, Oxytetracycline, Doxycycline and Minocycline(correlation coefficients 0.86-0.97). Correlation coefficients of susceptibility among penicillin analogues(Penicillin, Ampicillin, Carbenicillin and Cephalexin) ranged between 0.75-0.89. Correlation coefficients of susceptibility among aminoglycosides(Kanamycin, Gentamicin and Streptomycin) ranged between 0.09-0.51.

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First Report of Bacterial Spot Disease Caused by Pseudomonas capsici on Castor Bean in Korea (Pseudomonas capsici에 의한 아주까리 세균점무늬병의 국내 첫 보고)

  • Heeil Do;Seung Yeup Lee;Bang Wool Lee;Hyeonheui Ham;Mi-Hyun Lee;Young Kee Lee
    • Research in Plant Disease
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    • v.29 no.4
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    • pp.440-444
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    • 2023
  • In August 2021, water-soaking symptoms of bacterial spot disease were observed on castor bean in a field in Gangseo District, Busan. Bacteria isolated from the lesion when cultured on tryptic soy agar appeared to be nonmucoid and pale green. To confirm whether the isolates were the causative agent of the spot disease, they were inoculated onto healthy castor bean plants. The same symptoms were observed on the inoculated tissue, and the bacteria were reisolated from the lesion. Furthermore, the isolates were consistent with the biochemical and physiological features of Pseudomonas capsici. Sequencing analysis using 16S rRNA and housekeeping genes (gyrB, rpoD) showed that the isolates shared a high sequence similarity with P. capsici. These results confirmed that the strains belonged to P. capsici. To our knowledge, this is the first report of bacterial spot disease caused by P. capsici on castor bean in Korea.

Drug Resistance Patterns of the Bacterial Strains Isolated from Rural Areas and an Urban General Hospital (무의촌균주(無醫村菌株) 및 병원균주(病院菌株)의 항균제(抗菌劑) 내성(耐性) 양상(樣相)에 관(關)한 연구(硏究))

  • Rhee, Kwang-Ho;Kim, Ik-Sang;Shin, Hee-Sup;Cha, Chang-Yong;Lee, Seung-Hoon;Chang, Woo-Hyun;Lim, Jung-Kyoo
    • The Journal of the Korean Society for Microbiology
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    • v.15 no.1
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    • pp.19-32
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    • 1980
  • Besides the benefits of antimicrobial agents in the control of various infectious diseases, widespread and prolonged use of particular antimicrobial agents has brought about the increase of drug-resistant strains in a community and the profound changes in the pattern of infectious diseases. In Korea, there are some remote villages where no clinics and drug stores are available and the residents in those areas are assumed to have fewer chances to contact with antimicrobial agents. In the present study, the differences in susceptibilities to 14 antimicrobial agents between the isolates from rural areas(R) and Seoul National University Hospital(SNUH, H) were studied. The isolates and their numbers were Staphylococcus aureus, R;55, H;68), Enterococci(R;28, H;30), Escherichia coli(R;40, H;40), Enterobacter aerogenes(R;25, H;21) and Klebsiella pneunoniae(R;58, H;67). Minimal inhibitory concentrations(MIC's) of penicillin, ampicillin, carbenicillin, cephalexin, tetracycline, oxytetracyline, doxycycline, minocycline, gentamicin, kanamycin, streptomycin, erythromycin, troleandomycin and co-trimoxazole were determined by agar dilution method. I. Comparison of MIC's and resistant strain proportions between isolates from SNUH and rural areas. MIC's and/or resistant strain proportions of the isolates from SNUH were significantly higher than those of the isolates from rural areas in the cases of 1. S. aureus to doxycycline, streptomycin and kanamycin. 2. E. coli to penicillin, ampicillin, carbenicillin, tetracycline, oxytetracycline, doxycycline, minocycline, streptomycin, kanamycin, erythromycin and co-trimoxazole. 3. E. aerogences to carbenicillin, tetracycline, oxytetracycline, doxycycline, minocycline, streptomycin, kanamycin, genaamicin and co-trimoxazole. 4. K pneunoniae to penicillin, ampicillin, tetracycline, oxytetracycline, doxycycline, monocycline, streptomycin, kanamycine, gentamicin and co-trimoxazole. However, the mean MIC and resistant strain proportion of S. aureus to tetracycline were higher in isolates from rural areas than in those from SNUH and Enterococci showed no differences in susceptibilities to the antimicrobial agents between isolates from rural areas and from SNUH. Therefore, in general, differenes in susceptibility to these antimicrobial agents between the isolates from rural areas and SNUH were remarkably greater and broader in gram negative enteric bacteria. II. Multiple drug resistance pattern. Patterns and incidences of multiple drug resistance were studied with penicillin, ampicillin, tetracycline, cephalexin, gentamicin, streptomcin, kanamycin and co-trimoxazole in Enterococci, E. coli, E. aeroges and K. pneumoniae. There appeared significant differences in the incidence of multiply drug-resistant strains and multiple drug resistance patterns between the isolates from SNUH and rural areas in Enterococci, E. coli, E. aerogenes and K. pneumoniae. However, there was no difference in the incidence of multiply drug-resistant strains between isolates of S. aureus from SNUH and rural areas but the pattern of multiple resistance of the SNUH strains of S. aureus was diverse, while that of the rural strains was predominantly confined to penicillin-tetracycline combination. The incidence of multigly drug-resistant strains and diversity of their patterns were the highest in E. coli strains isolated from SNUH and there were no multiply drug resistant strrains in Enterococci and K. pneumoniae strains isolated from rural areas. The number of drug-resistance determinants was also different between the isolates from rural areas and SNUH. Most of the multiply drug-resistant strains of E. coli, E. aerogenes and K. pneumoniae isolated from SNUH were resistant to more than 3 kinds of antimicrobial agents, most frequently to ampicillin, tetracycline and streptomycin, while multiply drug-resistant strains from rural areas were resistant to 2 kinds of antimicrobial agents among ampicillin, tetracycline and streptomycin. With drug-resistant E. coli strains, resistance to tetracycline which was used most widely since 1951 was most frequently involved as a part of mutliple drug-resistance, followed by resistance to ampicillin and streptomycin. This strongly suggests that emergence of drug-restant strains in a community is directly dependent on the selective pressure exerted by the antimicrobial agent used. III. Cross resistance. Cross resistance of bacteria was studied among tetracycline penicillin, aminoglycoside and macrolide derivatives by analyzing correlation coefficients of sucseptibilities using the least square method. In this study, there were high correlations among the susceptibilities to related derivatives. It appears that the relatively low correlations in susceptibilities present in some cases are due to intrinsic resistance of E. aerogenes to penicillin, Enterococci to aminoglycoside and E. coli E. aerogenes and K. pneumoniae to macrolide derivatives.

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