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  1. Article: Methicillin-Resistant Staphylococcus aureus: A Growing Risk in the Hospital and in the Community.

    Raygada, Jose L / Levine, Donald P

    American health & drug benefits

    2014  Volume 2, Issue 2, Page(s) 86–95

    Abstract: Methicillin-resistant Staphylococcus aureus is a common and continuously growing cause of nosocomial and community-acquired infections. The type, disease severity, and clinical outcomes of these infections, as well as the genotypic and susceptibility ... ...

    Abstract Methicillin-resistant Staphylococcus aureus is a common and continuously growing cause of nosocomial and community-acquired infections. The type, disease severity, and clinical outcomes of these infections, as well as the genotypic and susceptibility patterns of the bacteria differ according to the setting in which the infection occurs-a healthcare facility or the community setting. The incidence of these infections in the community setting has been growing consistently in the past decade or so. In addition, resistance to the many current antibiotics used to treat these infections is also growing, further complicating management. Rapid-diagnosis tests and new therapeutic agents are constantly under investigation. The authors review the current understanding of the epidemiology, clinical manifestations, and management of methicillin-resistant Staphylococcus aureus infection, including the growing problem of resistance. In addition, they discuss promising diagnostic and therapeutic alternatives, as well as new control strategies to prevent its transmission or the development of infection among carriers.
    Language English
    Publishing date 2014-07-24
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2853721-X
    ISSN 1942-2970 ; 1942-2962
    ISSN (online) 1942-2970
    ISSN 1942-2962
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: [Características actuales de la coinfección con tuberculosis y el virus de la inmunodeficiencia humana en pacientes hospitalizados en Medellín, Colombia].

    Delgado-Raygada, José Eduardo / Sarmiento-Chía, Marjorie / Lucchetti-Rodríguez, Aldo / Vélez, Lázaro / Rueda, Zulma Vanessa / Maya, María Angélica / López, Lucelly / Ruiz, Lina

    Biomedica : revista del Instituto Nacional de Salud

    2019  Volume 39, Issue 1, Page(s) 224–228

    MeSH term(s) Adult ; Coinfection/complications ; Colombia ; Female ; HIV Infections/complications ; Hospitalization ; Humans ; Male ; Tuberculosis/complications ; Urban Health
    Language Spanish
    Publishing date 2019-03-31
    Publishing country Colombia
    Document type Comparative Study ; Letter
    ISSN 0120-4157
    ISSN 0120-4157
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Inability of a reserpine-based screen to identify strains overexpressing efflux pump genes in clinical isolates of Staphylococcus aureus.

    Frempong-Manso, Emmanuel / Raygada, Jose L / DeMarco, Carmen E / Seo, Susan M / Kaatz, Glenn W

    International journal of antimicrobial agents

    2008  Volume 33, Issue 4, Page(s) 360–363

    Abstract: Overexpression of efflux pump genes conferring multidrug resistance (MDR) in Staphylococcus aureus results in reduced susceptibility to select biocides, dyes and fluoroquinolones. Reserpine is commonly used as an inhibitor of MDR efflux pumps and ... ...

    Abstract Overexpression of efflux pump genes conferring multidrug resistance (MDR) in Staphylococcus aureus results in reduced susceptibility to select biocides, dyes and fluoroquinolones. Reserpine is commonly used as an inhibitor of MDR efflux pumps and previous work from our laboratory using a reserpine-based screen to identify clinical isolates with an efflux phenotype revealed that nearly one-half overexpressed norA-B-C, mepA or mdeA. The accuracy of reserpine in predicting efflux pump gene overexpression in clinical strains was examined in detail. Bloodstream isolates of S. aureus previously classified as non-effluxing strains by the reserpine screen underwent gene expression analysis using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The reserpine screen failed to identify many strains shown by qRT-PCR to overexpress one or more MDR efflux pump genes. Microdilution susceptibility testing with and without reserpine also failed to predict efflux pump activity. Although gene expression does not always correlate with protein translation, our results indicate that in clinical S. aureus isolates the use of reserpine to predict the contribution of efflux to reduced susceptibility is not dependable. All strains used in studies designed to assess MDR efflux pump gene expression in clinical isolates should be evaluated by a method independent of in vitro susceptibility testing.
    MeSH term(s) Bacteremia/microbiology ; Drug Resistance, Multiple, Bacterial ; Gene Expression Profiling ; Humans ; Membrane Transport Proteins/metabolism ; Microbial Sensitivity Tests/methods ; Reserpine/metabolism ; Reverse Transcriptase Polymerase Chain Reaction/methods ; Staphylococcal Infections/microbiology ; Staphylococcus aureus/isolation & purification ; Staphylococcus aureus/metabolism
    Chemical Substances Membrane Transport Proteins ; Reserpine (8B1QWR724A)
    Language English
    Publishing date 2008-12-21
    Publishing country Netherlands
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 1093977-5
    ISSN 1872-7913 ; 0924-8579
    ISSN (online) 1872-7913
    ISSN 0924-8579
    DOI 10.1016/j.ijantimicag.2008.10.016
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Multidrug efflux pump overexpression in Staphylococcus aureus after single and multiple in vitro exposures to biocides and dyes.

    Huet, Aurélie A / Raygada, Jose L / Mendiratta, Kabir / Seo, Susan M / Kaatz, Glenn W

    Microbiology (Reading, England)

    2008  Volume 154, Issue Pt 10, Page(s) 3144–3153

    Abstract: Biocides and dyes are commonly employed in hospital and laboratory settings. Many of these agents are substrates for multiple-drug resistance (MDR)-conferring efflux pumps of both Gram-positive and Gram-negative organisms. Several such pumps have been ... ...

    Abstract Biocides and dyes are commonly employed in hospital and laboratory settings. Many of these agents are substrates for multiple-drug resistance (MDR)-conferring efflux pumps of both Gram-positive and Gram-negative organisms. Several such pumps have been identified in Staphylococcus aureus, and mutants overexpressing the NorA and MepA MDR pumps following exposure to fluoroquinolones have been identified. The effect of exposure to low concentrations of biocides and dyes on the expression of specific pump genes has not been evaluated. Using quantitative reverse-transcription PCR we found that exposure of clinical isolates to low concentrations of a variety of biocides and dyes in a single step, or to gradually increasing concentrations over several days, resulted in the appearance of mutants overexpressing mepA, mdeA, norA and norC, with mepA overexpression predominating. Overexpression was frequently associated with promoter-region or regulatory protein mutations. Mutants having significant increases in MICs of common pump substrates but no changes in expression of studied pump genes were also observed; in these cases changes in expression of as-yet-unidentified MDR pump genes may have occurred. Strains of S. aureus that exist in relatively protected environments and are repeatedly exposed to sublethal concentrations of biocides can develop efflux-related resistance to those agents, and acquisition of such strains poses a threat to patients treated with antimicrobial agents that are also substrates for those pumps, such as ciprofloxacin and moxifloxacin.
    MeSH term(s) Anti-Bacterial Agents/pharmacology ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism ; Coloring Agents/pharmacology ; Disinfectants/pharmacology ; Drug Resistance, Multiple, Bacterial/drug effects ; Drug Resistance, Multiple, Bacterial/genetics ; Gene Expression Profiling ; Gene Expression Regulation, Bacterial ; Microbial Sensitivity Tests ; Multidrug Resistance-Associated Proteins/genetics ; Multidrug Resistance-Associated Proteins/metabolism ; Point Mutation ; RNA, Bacterial/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Staphylococcus aureus/drug effects ; Staphylococcus aureus/genetics ; Staphylococcus aureus/metabolism
    Chemical Substances Anti-Bacterial Agents ; Bacterial Proteins ; Coloring Agents ; Disinfectants ; Multidrug Resistance-Associated Proteins ; RNA, Bacterial
    Language English
    Publishing date 2008-09-23
    Publishing country England
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 1180712-x
    ISSN 1465-2080 ; 1350-0872
    ISSN (online) 1465-2080
    ISSN 1350-0872
    DOI 10.1099/mic.0.2008/021188-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Discovery of novel inhibitors of the NorA multidrug transporter of Staphylococcus aureus.

    Brincat, Jean Pierre / Carosati, Emanuele / Sabatini, Stefano / Manfroni, Giuseppe / Fravolini, Arnaldo / Raygada, Jose L / Patel, Diixa / Kaatz, Glenn W / Cruciani, Gabriele

    Journal of medicinal chemistry

    2011  Volume 54, Issue 1, Page(s) 354–365

    Abstract: Four novel inhibitors of the NorA efflux pump of Staphylococcus aureus, discovered through a virtual screening process, are reported. The four compounds belong to different chemical classes and were tested for their in vitro ability to block the efflux ... ...

    Abstract Four novel inhibitors of the NorA efflux pump of Staphylococcus aureus, discovered through a virtual screening process, are reported. The four compounds belong to different chemical classes and were tested for their in vitro ability to block the efflux of a well-known NorA substrate, as well as for their ability to potentiate the effect of ciprofloxacin (CPX) on several strains of S. aureus, including a NorA overexpressing strain. Additionally, the MIC values of each of the compounds individually are reported. A structure-activity relationship study was also performed on these novel chemotypes, revealing three new compounds that are also potent NorA inhibitors. The virtual screening procedure employed FLAP, a new methodology based on GRID force field descriptors.
    MeSH term(s) Anti-Bacterial Agents/chemical synthesis ; Anti-Bacterial Agents/chemistry ; Anti-Bacterial Agents/pharmacology ; Bacterial Proteins/antagonists & inhibitors ; Benzimidazoles/chemical synthesis ; Benzimidazoles/chemistry ; Benzimidazoles/pharmacology ; Ciprofloxacin/pharmacology ; Databases, Factual ; Drug Resistance, Bacterial ; Drug Synergism ; Ethidium/antagonists & inhibitors ; Microbial Sensitivity Tests ; Models, Molecular ; Multidrug Resistance-Associated Proteins/antagonists & inhibitors ; Phenyl Ethers/chemical synthesis ; Phenyl Ethers/chemistry ; Phenyl Ethers/pharmacology ; Propanolamines/chemical synthesis ; Propanolamines/chemistry ; Propanolamines/pharmacology ; Quantitative Structure-Activity Relationship ; Staphylococcus aureus/drug effects ; Staphylococcus aureus/metabolism ; Structure-Activity Relationship ; Sulfonamides/chemical synthesis ; Sulfonamides/chemistry ; Sulfonamides/pharmacology
    Chemical Substances Anti-Bacterial Agents ; Bacterial Proteins ; Benzimidazoles ; Multidrug Resistance-Associated Proteins ; Phenyl Ethers ; Propanolamines ; Sulfonamides ; NorA protein, Staphylococcus (133135-40-7) ; Ciprofloxacin (5E8K9I0O4U) ; Ethidium (EN464416SI)
    Language English
    Publishing date 2011-01-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/jm1011963
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations.

    Janeway, Katherine A / Kim, Su Young / Lodish, Maya / Nosé, Vânia / Rustin, Pierre / Gaal, José / Dahia, Patricia L M / Liegl, Bernadette / Ball, Evan R / Raygada, Margarita / Lai, Angela H / Kelly, Lorna / Hornick, Jason L / O'Sullivan, Maureen / de Krijger, Ronald R / Dinjens, Winand N M / Demetri, George D / Antonescu, Cristina R / Fletcher, Jonathan A /
    Helman, Lee / Stratakis, Constantine A

    Proceedings of the National Academy of Sciences of the United States of America

    2010  Volume 108, Issue 1, Page(s) 314–318

    Abstract: Carney-Stratakis syndrome, an inherited condition predisposing affected individuals to gastrointestinal stromal tumor (GIST) and paraganglioma, is caused by germline mutations in succinate dehydrogenase (SDH) subunits B, C, or D, leading to dysfunction ... ...

    Abstract Carney-Stratakis syndrome, an inherited condition predisposing affected individuals to gastrointestinal stromal tumor (GIST) and paraganglioma, is caused by germline mutations in succinate dehydrogenase (SDH) subunits B, C, or D, leading to dysfunction of complex II of the electron transport chain. We evaluated the role of defective cellular respiration in sporadic GIST lacking mutations in KIT or PDGFRA (WT). Thirty-four patients with WT GIST without a personal or family history of paraganglioma were tested for SDH germline mutations. WT GISTs lacking demonstrable SDH genetic inactivation were evaluated for SDHB expression by immunohistochemistry and Western blotting and for complex II activity. For comparison, SDHB expression was also determined in KIT mutant and neurofibromatosis-1-associated GIST, and complex II activity was also measured in SDH-deficient paraganglioma and KIT mutant GIST; 4 of 34 patients (12%) with WT GIST without a personal or family history of paraganglioma had germline mutations in SDHB or SDHC. WT GISTs lacking somatic mutations or deletions in SDH subunits had either complete loss of or substantial reduction in SDHB protein expression, whereas most KIT mutant GISTs had strong SDHB expression. Complex II activity was substantially decreased in WT GISTs. WT GISTs, particularly those in younger patients, have defects in SDH mitochondrial complex II, and in a subset of these patients, GIST seems to arise from germline-inactivating SDH mutations. Testing for germline mutations in SDH is recommended in patients with WT GIST. These findings highlight a potential central role of SDH dysregulation in WT GIST oncogenesis.
    MeSH term(s) Adolescent ; Blotting, Western ; Cell Respiration/genetics ; Cell Respiration/physiology ; DNA Mutational Analysis ; Electron Transport Complex II/genetics ; Electron Transport Complex II/metabolism ; Gastrointestinal Stromal Tumors/enzymology ; Genetic Predisposition to Disease/genetics ; Germ-Line Mutation/genetics ; Humans ; Immunohistochemistry ; Paraganglioma/enzymology ; Polymorphism, Single Nucleotide ; Protein Subunits/genetics ; Proto-Oncogene Proteins c-kit/genetics ; Receptor, Platelet-Derived Growth Factor alpha/genetics ; Succinate Dehydrogenase/genetics ; Succinate Dehydrogenase/metabolism ; Syndrome
    Chemical Substances Protein Subunits ; Electron Transport Complex II (EC 1.3.5.1) ; Succinate Dehydrogenase (EC 1.3.99.1) ; Proto-Oncogene Proteins c-kit (EC 2.7.10.1) ; Receptor, Platelet-Derived Growth Factor alpha (EC 2.7.10.1)
    Language English
    Publishing date 2010-12-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.1009199108
    Database MEDical Literature Analysis and Retrieval System OnLINE

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