• Title/Summary/Keyword: new antibiotics

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Surgical Treatment of Native Valve Endocarditis (감염성 심내막염의 외과적 치료)

  • Kim, Ae-Jung;Kim, Min-Ho;Kim, Gong-Su
    • Journal of Chest Surgery
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    • v.28 no.9
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    • pp.822-828
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    • 1995
  • This paper reports 15 native valve endocarditis cases had surgical operation in the past 10 years at the department of Cardiovascular and Thoracic Surgery, Chonbuk National University Hospital. In this study, 10 cases out of 15 were in class I or II by the New York Heart Association functional classification. None of the cases had a history of taking addictive drugs. Five cases were congenital heart disease, three cases were rheumatic heart disease and two cases were degenerative heart disease. Thus 10 cases had the underlying disease. All cases had antibiotics treatment for 3 to 6 weeks before operation. In the culture test, only four cases were positive in the blood culture and one case was positive in the excised valve culture. Organisms on blood and valve culture were Streptococcus epidermis, Streptococcus viridans, Staphylococcus aureus and Staphylococcus epidermidis. In the 10 cases without ventricular septal defect, the aortic valve was involved in four, mitral in four, both in two and involved valves in the 5 cases with ventricular septal defect were tricuspid in three, pulmonic in two. Eight cases had operation because they showed moderate congestive heart failure due to valvular insufficiency and vegetation with or without embolism. Seven cases had operation because they showed persistent or progressive congestive heart failure and/or uncontrolled infection. Five cases with ventricular septal defect underwent the closure of ventricular septal defect, vegetectomy and leaflet excision of the affected valves without valve replacement. In the cases without ventricular septal defect, the affected valves were replaced with St. Jude mechanical prosthesis. Postoperative complications were recurrent endocarditis in two, embolism in one, allergic vasculitis in two, spleen rupture in one and postpericardiotomy syndrome in one. At the first postoperative day, one case died of cerebral embolism. At the 11th postoperative month, one case died of recurrent endocarditis and paravalvular leakage in spite of a couple of aortic valve replacement. In the survived cases[13 cases in this study , all cases but one became class I or II by the New York Heart Association functional classification.

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Sclareol Protects Staphylococcus aureus-Induced Lung Cell Injury via Inhibiting Alpha-Hemolysin Expression

  • Ouyang, Ping;Sun, Mao;He, Xuewen;Wang, Kaiyu;Yin, Zhongqiong;Fu, Hualin;Li, Yinglun;Geng, Yi;Shu, Gang;He, Changliang;Liang, Xiaoxia;Lai, Weiming;Li, Lixia;Zou, Yunfeng;Song, Xu;Yin, Lizi
    • Journal of Microbiology and Biotechnology
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    • v.27 no.1
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    • pp.19-25
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    • 2017
  • Staphylococcus aureus (S. aureus) is a common gram-positive bacterium that causes serious infections in humans and animals. With the continuous emergence of methicillin-resistant S. aureus (MRSA) strains, antibiotics have limited efficacy in treating MRSA infections. Accordingly, novel agents that act on new targets are desperately needed to combat these infections. S. aureus alpha-hemolysin plays an indispensable role in its pathogenicity. In this study, we demonstrate that sclareol, a fragrant chemical compound found in clary sage, can prominently decrease alpha-hemolysin secretion in S. aureus strain USA300 at sub-inhibitory concentrations. Hemolysis assays, western-blotting, and RT-PCR were used to detect the production of alpha-hemolysin in the culture supernatant. When USA300 was co-cultured with A549 epithelial cells, sclareol could protect the A549 cells at a final concentration of $8{\mu}g/ml$. The protective capability of sclareol against the USA300-mediated injury of A549 cells was further shown by cytotoxicity assays and live/dead analysis. In conclusion, sclareol was shown to inhibit the production of S. aureus alpha-hemolysin. Sclareol has potential for development as a new agent to treat S. aureus infections.

Synergistic Effect of Brazilein in Combination with Hygromycin-b against Staphylococcus aureus (메티실린-내성 포도상구균에 대하여 Brazilein 혼합에 따른 항생제 Hygromycin-b의 상승효과)

  • Lee, Young Seob;Lee, Dae Young;An, Tae Jin;Lee, Jeong Hoon;Ahn, Young Sup;Cha, Seon Woo;Mun, Su Hyun;Kang, Ok Hwa;Kwon, Dong Yeul;Han, Sin Hee
    • Korean Journal of Medicinal Crop Science
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    • v.22 no.6
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    • pp.504-509
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    • 2014
  • Methicillin-resistant Staphylococcus aureus (MRSA) is a substantial contributor to morbidity and mortality. In search of a natural products capable of inhibiting this multidrug resistant bacteria, we have investigated the antimicrobial activity of brazilein (BRZ) isolated from Caesalpinia sappan L. (Leguminosae) against 8 different strains of Staphylococcus aureus (S. aureus). New antimicrobial activity was found using the minimum inhibitory concentrations (MICs), broth dilution as well as checkerboard method. Against the 8 strains, the minimum inhibitory concentrations of BRZ were in the range of $62.5-500{\mu}g/mL$. From those results we performed the checkerboard test to determine the synergism of BRZ in combination with Hygromycin-b (HgB) against 4 strains. The combined activity of BRZ and HgB against 4 strains resulted in a fractional inhibitory concentrations index (FICI) ranging from 0.18-0.5. The effect of BRZ with HgB was found to be synergistic. We found that BRZ reduced the MICs of HgB. BRZ and HgB could lead to the development of new combination antibiotics against MRSA infection.

Action Mechanism of LB10522, a New Catechol-Substituted Cephalosporin (카테콜 치환체를 가진 세파로스포린계 항생제 LB10522의 작용기전)

  • Kim, Mu-Yong;Oh, Jeong-In;Paek, Kyoung-Sook;Kim, In-Chull;Kwak, Jin-Hwan
    • YAKHAK HOEJI
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    • v.40 no.1
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    • pp.102-111
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    • 1996
  • LB10522 is a new parenteral broad spectrum cephalosporin with a catechol moiety at C-7 position of beta-lactam ring. This compound can utilize tonB-dependent iron transp ort system in addition to porin proteins to enter bacterial periplasmic space and access to penicillin-binding proteins (PBPs) which are the lethal targets of ${\beta}$-lactam antibiotics. The chelating activity of LB10522 to metal iron was measured by spectrophotometrically scanning the absorbance from 200 to 900nm. When $FeCl_3$ was added, optical density was increased between 450 and 800nm. LB10522 was more active against gram-negative strains in iron-depleted media than in iron-replete media. This is due to the increased expression of iron transport channels in iron-depleted condition. LB10522 showed a similar activity against E. coli DC2 (permeability mutant) and E. coli DCO (wild type strain) in both iron-depleted and iron-replete media, indicating a minimal permeaility barrier for LB10522 uptake. LB10522 had high affinities to PBP 3 and PBP 1A, 1B of E. coli. By blocking these proteins, LB10522 caused inhibition of cell division and the eventual death of cells. This result was correlated well with the morphological changes in E. coli exposed to LB10522. Although the in vitro MIC of LB10522 against P. aeruginosa 1912E mutant (tonB) was 8-times higher than that of the P. aeruginosa 1912E parent strain, LB10522 showed a similar in vivo protection efficacy against both strains in the mouse systemic infection model. This result suggested that tonB mutant, which requires a high level of iron for normal growth, might have a difficulty in surviving in their host with an iron-limited environment.

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Critical Care Medicine (호흡기내과 의사를 위한 Respiratory Review of 2010)

  • Park, Jie-Hae;Chae, Jin-Nyeong;Choi, Won-Il
    • Tuberculosis and Respiratory Diseases
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    • v.69 no.2
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    • pp.75-80
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    • 2010
  • The year of 2009~2010 brought a number of concepts and new ideas were evaluated with promising results. However, some studies that challenged many beliefs. In acute respiratory distress syndrome (ARDS), recent clinical studies took into consideration of pathophysiologic changes of respiratory system compliance. Meta-analysis of positive end-expiratory pressure trials showed survival benefit of high positive end-expiratory pressure in ARDS. Until now, prone positioning did not show survival benefit in patients with ARDS. Extracorporeal membrane oxygenation (ECMO) based management improved survival in patients with severe ARDS. ECMO can be a management option in severe ARDS. Sedation is a standard practice in critically ill patients needing mechanical ventilation. However, Danish group reported less sedation of critically ill patients receiving mechanical ventilation was associated with an increase in days without ventilation. Although this single center study has some limitations, the overall results are promising. Use of maximal sterile barrier precautions (mask, sterile gown, sterile gloves, and large sterile drapes) with chlorhexidine-impregnated dressing reduced central venous catheter related infection. Selective oropharyngeal decontamination (application of topical antibiotics in the oropharynx) reduced the mortality rate of an intensive care unit (ICU) population. Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation (NICE-SUGAR) trial reported intensive glucose control increased mortality among adults in the ICU. Some of the results of above papers are promising. However, some ideas may need for more frequent individual assessment and increase the workload of ICU staffs. Before implementation of new practice in ICU, we should take into consideration of individual hospital situation including human and material resources.

Multi-epitope vaccine against drug-resistant strains of Mycobacterium tuberculosis: a proteome-wide subtraction and immunoinformatics approach

  • Md Tahsin Khan;Araf Mahmud;Md. Muzahidul Islam;Mst. Sayedatun Nessa Sumaia;Zeaur Rahim;Kamrul Islam;Asif Iqbal
    • Genomics & Informatics
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    • v.21 no.3
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    • pp.42.1-42.23
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    • 2023
  • Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis, one of the most deadly infections in humans. The emergence of multidrug-resistant and extensively drug-resistant Mtb strains presents a global challenge. Mtb has shown resistance to many frontline antibiotics, including rifampicin, kanamycin, isoniazid, and capreomycin. The only licensed vaccine, Bacille Calmette-Guerin, does not efficiently protect against adult pulmonary tuberculosis. Therefore, it is urgently necessary to develop new vaccines to prevent infections caused by these strains. We used a subtractive proteomics approach on 23 virulent Mtb strains and identified a conserved membrane protein (MmpL4, NP_214964.1) as both a potential drug target and vaccine candidate. MmpL4 is a non-homologous essential protein in the host and is involved in the pathogen-specific pathway. Furthermore, MmpL4 shows no homology with anti-targets and has limited homology to human gut microflora, potentially reducing the likelihood of adverse effects and cross-reactivity if therapeutics specific to this protein are developed. Subsequently, we constructed a highly soluble, safe, antigenic, and stable multi-subunit vaccine from the MmpL4 protein using immunoinformatics. Molecular dynamics simulations revealed the stability of the vaccine-bound Tolllike receptor-4 complex on a nanosecond scale, and immune simulations indicated strong primary and secondary immune responses in the host. Therefore, our study identifies a new target that could expedite the design of effective therapeutics, and the designed vaccine should be validated. Future directions include an extensive molecular interaction analysis, in silico cloning, wet-lab experiments, and evaluation and comparison of the designed candidate as both a DNA vaccine and protein vaccine.

Intestinal Growth and Development of Weanling Pigs in Response to Dietary Supplementation of Antibiotics, Phytogenic Products and Brewer's Yeast plus Bacillus Spores

  • Lee, C.-Young;Lim, Jung-Won;Ko, Young-Hyun;Kang, Sun-Young;Park, Man-Jong;Ko, Tae-Gu;Lee, Ji-Hoon;Hyun, Young;Jeong, Kyu-Sik;Jang, In-Surk
    • Journal of Animal Science and Technology
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    • v.53 no.3
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    • pp.227-235
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    • 2011
  • A total of 96 crossbred weanling barrows aged 21 days were randomly allocated to 32 pens of a new nursery to investigate the effects of antibiotics, phytogenics, and probiotics on intestinal growth and development. The animals were fed a set of three-phase basal diets containing 0.3% zinc oxide (CON) or the basal diets supplemented with 353 ppm of a combination of tiamulin, neomycin, chlortetracycline, and oxytetracycline (ANTI), 75 ppm triterpenoid saponin plus 150 ppm mixed saccharides (HERB; Sacchapin$^{(R)}$), or $1{\times}10^7$ brewer's yeasts plus $8{\times}10^7$ spores of each of Bacillus licheniformis and Bacillus subtilis per kilogram feed (PROBIO; Yeasture Plus 2B$^{(R)}$) for five weeks. Thirty-two pigs representing as many pens were slaughtered at the end of the feeding trial, after which morphological measures and digestive enzyme activities of intestinal mucosa were determined. Weight gain and gain:feed of the pigs were not affected by the dietary treatments (TRT) during the overall feeding trial. Total intestinal length was greater in PROBIO than in ANTI (P<0.05). Wet mucosa weight of the duodenum was not affected by TRT. However, jejunal mucosa weight was greater in PROBIO than in any other group sum of mucosa weights of the duodenum and jejunum was greater (P<0.05) in PROBIO than in ANTI and HERB. The height and width of duodenal villus were not affected by TRT, but crypt depth decreased (P<0.05) in response to HERB and PROBIO vs CON. Specific activities of alkaline phosphatase, sucrase, maltase, lactase, and leucine aminopeptidase in the duodenum and jejunum were not changed by TRT. In conclusion, results suggest that the present dietary treatments have no effects on growth performance of weanling pigs and that of PROBIO enhances intestinal growth and development under a clean experimental setting.

Construction and Analysis of a DNA Microarray for the Screening of Biosynthetic Genes of Secondary-Metabolites formation in Streptomyces (방선균 유래 이차대사 생합성 유전자 분석용 DNA Microarray 제작 및 해석)

  • Nam Soo Jung;Kang Dae-Kyung;Rhee Ki Hyeong;Kim Jong-Hee;Kang Sang Sun;Chang Yong Keun;Hong Soon-Kwang
    • Korean Journal of Microbiology
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    • v.41 no.2
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    • pp.105-111
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    • 2005
  • Streptomyces produces many kinds of secondary-metabolites including antibiotics. Screening of a new compound and elucidation of a biosynthetic pathway for the secondary metabolites are very important fields of biology, however, there is a main problem that most of the identified compounds are already researched compounds. To solve these problems, a microarray system that is based on the data related to the biosynthetic genes for secondary-metabolites was designed. For the main contents of DNA microarray, the important genes for the bio-synthesis of aminoglycosides, polyenes group, enediyne group, alpha-glucosidase inhibitors, glycopeptide group, and orthosomycin group were chosen. A DNA microarray with 69 genes that were involved in the bio-synthesis for the antibiotics mentioned above was prepared. The usability of the DNA microarray was confirmed with the chromosomal DNA and total RNA extracted from S. coelicolor whose genomic sequence had already been reported.

The absorption and excretion times of carp, Cyprinus carpio, treatment with oxolinic acid (향어에서의 oxolinic acid 흡수와 배설속도)

  • Jeong, Hyun-Do;Ha, Jai-Yi;Huh, Min-Do;Chung, Joon-Ki
    • Journal of fish pathology
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    • v.5 no.2
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    • pp.135-142
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    • 1992
  • The absorption and excretion times of oxolinic acid(OX) used in farms as new aquatic antibiotics commonly were evaluated with determination of the effects of water temperature and feeding to parameters by using the bioassay technique. On the same time, antibacterial activity and the complex formation of oxolinic acid with serum proteins of two different fishes were compared to those oxytetracycline(OTC). With more than 10 times lower MIC values than those of OTC in the strains among 13 analyzed fish pathogens. OX did not show the decresed antibacterial activity by the binding of serum proteins in carp and tilapia. It implies more powerful potential of OX as aquatic medicine OTC. The serum concentration of OX after different administrations the oral, i.m., i.v and dipping methods were compared. The higher beginning concentration in serum and faster excretion times were obserbed in i.m. and dipping methods respectively. In the oral and i.m. administration, peak serum concentration after 24-48 hrs and slow excretion times demonstrated in both methods. These pharmacokinetic characteristics similar at $30^{\circ}C$ and $20^{\circ}C$ water temperature conditions, however, beginning serum concentration of OX in fish dipped in $50mg/\ell$ sol after starvation for 2 wks was appeared lower than those of fed fish. It suggests the importance of biological condition of the gill or skin for absorption of antibiotics after dipping administration.

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NDP-sugar production and glycosylation of ${\varepsilon}$-rhodomycinone in Streptomyces venezuelae (Streptomyces Peucetius에서의 ${\varepsilon}$-rhodomycinone 추출 및 이종균주에서의 rhodomycin D 생산 연구)

  • Park, Sung-Hee;Cha, Min-Ho;Kim, Eun-Jung;Yoon, Yeo-Joon;Sohng, Jae-Kyung;Lee, Hee-Chan;Liou, Kwang-Kyoung;Kim, Byung-Gee
    • KSBB Journal
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    • v.23 no.1
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    • pp.44-47
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    • 2008
  • Anthracycline antibiotics doxorubicin (DXR) is clinically important cancer therapeutic agent produced by Streptomyces peucetius. DXR result by further metabolism of rhodomycin D (RHOD) and require a deoxy-sugar component for their biological activity. In this study, production of TDP-L-daunosamine and its attachment to ${\varepsilon}$-rhodomycinone (RHO) to generate RHOD has been achieved by bioconversion in Streptomyces venezuelae that bears eleven genes. S. peucetius seven genes (dnmUTJVZQS) were transformed by plasmid and S. venezuelae two genes desIII, IV and two more S. peucetius drrA, B genes were integrated into chromosomal DNA. To generate the feeding substrate RHO, 6L S. peucetius grown on agar plate was harvested, extracted with organic solvent and then purified using preparative HPLC. Recombinant S. venezuelae grown on agar plate containing RHO was harvested and its n-butanol soluble components were extracted. The glycosylated product of aromatic polyketide RHO using heterologous host S. venezuelae presents the minimal information for TDP-L-daunosamine biosynthesis and its attachment onto aglycone. Moreover, the structure of auxiliary protein, DnrQ, was predicted by fold recognition and homology modeling in this study. This is a general approach to further expand of new glycosides of antitumor anthracycline antibiotics.