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Therapeutics and Prevention

  • Open Access
    A Novel, Rapid, and Low-Volume Assay for Therapeutic Drug Monitoring of Posaconazole and Other Long-Chain Azole-Class Antifungal Drugs
    Observation | Therapeutics and Prevention
    A Novel, Rapid, and Low-Volume Assay for Therapeutic Drug Monitoring of Posaconazole and Other Long-Chain Azole-Class Antifungal Drugs

    This work describes an effective assay for TDM of long-chain azole-class antifungal drugs that can be used in diluted human serum samples. This assay will provide a quick, cost-effective method for monitoring concentrations of drugs such as posaconazole that exhibit well-documented pharmacokinetic variability. Our rGO-aptamer assay has the potential to improve health care for those struggling to treat fungal infections in rural or...

    Gregory R. Wiedman, Yanan Zhao, David S. Perlin
  • Open Access
    Development of an Opsonophagocytic Killing Assay Using HL-60 Cells for Detection of Functional Antibodies against <em>Streptococcus pyogenes</em>
    Research Article | Therapeutics and Prevention
    Development of an Opsonophagocytic Killing Assay Using HL-60 Cells for Detection of Functional Antibodies against Streptococcus pyogenes

    Measuring functional opsonic antibodies against group A streptococci is an important component of the clinical development path for effective vaccines. Prior studies have used an assay developed over 60 years ago that relied on whole human blood as the source of phagocytes and complement, both of which are critical components of antibody-mediated killing assays. In this study, we adapted an assay that uses the HL-60 human promyelocytic...

    Sanaz Salehi, Claudia M. Hohn, Thomas A. Penfound, James B. Dale
  • Open Access
    Fh15 Blocks the Lipopolysaccharide-Induced Cytokine Storm While Modulating Peritoneal Macrophage Migration and CD38 Expression within Spleen Macrophages in a Mouse Model of Septic Shock
    Research Article | Therapeutics and Prevention
    Fh15 Blocks the Lipopolysaccharide-Induced Cytokine Storm While Modulating Peritoneal Macrophage Migration and CD38 Expression within Spleen Macrophages in a Mouse Model of Septic Shock

    Sepsis is a potentially life-threatening complication of an infection. Sepsis is mostly the consequence of systemic bacterial infections leading to exacerbated activation of immune cells by bacterial products, resulting in enhanced release of inflammatory mediators. Lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, is a critical factor in the pathogenesis of sepsis, which is sensed by Toll-...

    Marcos J. Ramos-Benitez, Caleb Ruiz-Jimenez, Jose J. Rosado-Franco, Willy D. Ramos-Pérez, Loyda B. Mendez, Antonio Osuna, Ana M. Espino
  • Open Access
    Vitamin E Increases Antimicrobial Sensitivity by Inhibiting Bacterial Lipocalin Antibiotic Binding
    Research Article | Therapeutics and Prevention
    Vitamin E Increases Antimicrobial Sensitivity by Inhibiting Bacterial Lipocalin Antibiotic Binding

    Bacteria exposed to stress mediated by sublethal antibiotic concentrations respond by adaptive mechanisms leading to an overall increase of antibiotic resistance. One of these mechanisms involves the release of bacterial proteins called lipocalins, which have the ability to sequester antibiotics in the extracellular space before they reach bacterial cells. We speculated that interfering with lipocalin-mediated antibiotic binding could...

    Marwa M. Naguib, Miguel A. Valvano
  • Open Access
    Acquired Nisin Resistance in <em>Staphylococcus aureus</em> Involves Constitutive Activation of an Intrinsic Peptide Antibiotic Detoxification Module
    Research Article | Therapeutics and Prevention
    Acquired Nisin Resistance in Staphylococcus aureus Involves Constitutive Activation of an Intrinsic Peptide Antibiotic Detoxification Module

    NIS and related bacteriocins are of interest as candidates for the treatment of human infections caused by Gram-positive pathogens such as Staphylococcus aureus. An important liability of NIS in this regard is the ease with which S. aureus acquires resistance. Here we establish that this organism...

    Christopher P. Randall, Arya Gupta, Bret Utley-Drew, Siu Yi Lee, Genevieve Morrison-Williams, Alex J. O’Neill
  • Open Access
    Improving Our Understanding of <em>Salmonella enterica</em> Serovar Paratyphi B through the Engineering and Testing of a Live Attenuated Vaccine Strain
    Research Article | Therapeutics and Prevention
    Improving Our Understanding of Salmonella enterica Serovar Paratyphi B through the Engineering and Testing of a Live Attenuated Vaccine Strain

    We developed a live attenuated Salmonella enterica serovar Paratyphi B vaccine that conferred protection in mice against challenge with S. Paratyphi B sensu stricto and S. Paratyphi B Java, which are the causes of enteric fever and gastroenteritis, respectively. Currently, the incidence of invasive S. Paratyphi B sensu stricto...

    Ellen E. Higginson, Girish Ramachandran, Tracy H. Hazen, Dane A. Kania, David A. Rasko, Marcela F. Pasetti, Myron M. Levine, Sharon M. Tennant
  • Open Access
    Glycerol Monolaurate (GML) and a Nonaqueous Five-Percent GML Gel Kill <em>Bacillus</em> and <em>Clostridium</em> Spores
    Editor's Pick Research Article | Therapeutics and Prevention
    Glycerol Monolaurate (GML) and a Nonaqueous Five-Percent GML Gel Kill Bacillus and Clostridium Spores

    Bacillus and Clostridium spores are known to be highly resistant to killing, persisting on environmental and human body surfaces for long periods of time. In favorable environments, these spores may germinate and cause human diseases. It is thus important to identify agents that can be used on both environmental and human skin and mucosal surfaces and that are effective in killing spores. We previously showed that the...

    Patrick M. Schlievert, Samuel H. Kilgore, Gabriela M. Kaus, Theresa D. Ho, Craig D. Ellermeier
  • Open Access
    The Fourth International Neonatal and Maternal Immunization Symposium (INMIS 2017): Toward Integrating Maternal and Infant Immunization Programs
    Meeting Highlights | Therapeutics and Prevention
    The Fourth International Neonatal and Maternal Immunization Symposium (INMIS 2017): Toward Integrating Maternal and Infant Immunization Programs

    This report provides an overview of the proceedings of the 4th International Maternal and Neonatal Immunization Symposium, where presentations focused on the state-of-the-art research on the development and implementation of vaccines given during pregnancy for the protection of mothers and infants.

    Flor M. Munoz, Pierre Van Damme, Ener Dinleyici, Ed Clarke, Beate Kampmann, Paul T. Heath, Ofer Levy, Elke Leuridan, Clare Cutland, Ajoke Sobanjo-ter Meulen, Arnaud Marchant
  • Open Access
    Hydroxypropyl-Beta-Cyclodextrin Reduces Inflammatory Signaling from Monocytes: Possible Implications for Suppression of HIV Chronic Immune Activation
    Research Article | Therapeutics and Prevention
    Hydroxypropyl-Beta-Cyclodextrin Reduces Inflammatory Signaling from Monocytes: Possible Implications for Suppression of HIV Chronic Immune Activation

    Chronic immune activation is a hallmark of HIV infection and is often not controlled even in patients under antiretroviral therapy. Indeed, chronic diseases with inflammatory pathogenesis are being reported as major causes of death for HIV-infected persons. Hydroxypropyl-beta cyclodextrin (HP-BCD) is a cholesterol-sequestering drug that inhibits HIV replication and infectivity in vitro and in vivo. Recent studies have...

    Flávio Lemos Matassoli, Ihid Carneiro Leão, Bruno Braz Bezerra, Richard B. Pollard, Dieter Lütjohann, James E. K. Hildreth, Luciana Barros de Arruda
  • Open Access
    Alexidine Dihydrochloride Has Broad-Spectrum Activities against Diverse Fungal Pathogens
    Research Article | Therapeutics and Prevention
    Alexidine Dihydrochloride Has Broad-Spectrum Activities against Diverse Fungal Pathogens

    The prevalence of fungal infections has seen a rise in the past decades due to advances in modern medicine leading to an expanding population of device-associated and immunocompromised patients. Furthermore, the spectrum of pathogenic fungi has changed, with the emergence of multidrug-resistant strains such as C. auris. High mortality related to fungal infections...

    Zeinab Mamouei, Abdullah Alqarihi, Shakti Singh, Shuying Xu, Michael K. Mansour, Ashraf S. Ibrahim, Priya Uppuluri

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