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  • 1
    Language: English
    In: 2014, Vol.8(12), p.e3347
    Description: Despite major attempts to prevent cholera transmission, millions of people worldwide still must address this devastating disease. Cholera research has so far mainly focused on the causative agent, the bacterium Vibrio cholerae , or on disease treatment, but rarely were results from both fields interconnected. Indeed, the treatment of this severe diarrheal disease is mostly accomplished by oral rehydration therapy (ORT), whereby water and electrolytes are replenished. Commonly distributed oral rehydration salts also contain glucose. Here, we analyzed the effects of glucose and alternative carbon sources on the production of virulence determinants in the causative agent of cholera, the bacterium Vibrio cholerae during in vitro experimentation. We demonstrate that virulence gene expression and the production of cholera toxin are enhanced in the presence of glucose or similarly transported sugars in a ToxR-, TcpP- and ToxT-dependent manner. The virulence genes were significantly less expressed if alternative non-PTS carbon sources, including rice-based starch, were utilized. Notably, even though glucose-based ORT is commonly used, field studies indicated that rice-based ORT performs better. We therefore used a spatially explicit epidemiological model to demonstrate that the better performing rice-based ORT could have a significant impact on epidemic progression based on the recent outbreak of cholera in Haiti. Our results strongly support a change of carbon source for the treatment of cholera, especially in epidemic settings. ; Cholera research has so far mainly focused on the causative agent, the bacterium , or on disease treatment, but rarely were results from both fields interconnected. Indeed, the treatment of this severe diarrheal disease is mostly accomplished by oral rehydration therapy (ORT). ORT aims at rehydrating patients through the provision of water and oral rehydration salts; the latter being composed of electrolytes as well as glucose as a carbon source. Although glucose-based ORS is commonly used to treat diarrheal diseases and is recommended by the WHO, field studies on cholera indicated that rice-based ORT performs better than glucose-based ORT. Here, we investigated the impact that glucose, starch, or other carbon sources exert on . We demonstrated that glucose leads to an increased expression of the major virulence genes in the pathogen and, accordingly, to an enhanced production of cholera toxin during experimentation. Because the cholera toxin is primarily responsible for the severe symptoms that are associated with the disease, our study highlights the negative effects of glucose-based ORT. Next, we used a spatially explicit epidemiological model to demonstrate that the better performing rice-based ORS could have a significant impact on epidemic progression based on the recent outbreak of cholera in Haiti.
    Keywords: Research Article ; Biology And Life Sciences ; Medicine And Health Sciences
    ISSN: 19352727
    E-ISSN: 1935-2735
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  • 2
    Language: English
    In: Science translational medicine, 15 January 2014, Vol.6(219), pp.219ra7
    Description: Inflammatory monocyte-derived effector cells play an important role in the pathogenesis of numerous inflammatory diseases. However, no treatment option exists that is capable of modulating these cells specifically. We show that infused negatively charged, immune-modifying microparticles (IMPs), derived from polystyrene, microdiamonds, or biodegradable poly(lactic-co-glycolic) acid, were taken up by inflammatory monocytes, in an opsonin-independent fashion, via the macrophage receptor with collagenous structure (MARCO). Subsequently, these monocytes no longer trafficked to sites of inflammation; rather, IMP infusion caused their sequestration in the spleen through apoptotic cell clearance mechanisms and, ultimately, caspase-3-mediated apoptosis. Administration of IMPs in mouse models of myocardial infarction, experimental autoimmune encephalomyelitis, dextran sodium sulfate-induced colitis, thioglycollate-induced peritonitis, and lethal flavivirus encephalitis markedly reduced monocyte accumulation at inflammatory foci, reduced disease symptoms, and promoted tissue repair. Together, these data highlight the intricate interplay between scavenger receptors, the spleen, and inflammatory monocyte function and support the translation of IMPs for therapeutic use in diseases caused or potentiated by inflammatory monocytes.
    Keywords: Microspheres ; Inflammation -- Immunology ; Monocytes -- Immunology
    ISSN: 19466234
    E-ISSN: 1946-6242
    Library Location Call Number Volume/Issue/Year Availability
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  • 3
    Language: English
    Description: Despite major attempts to prevent cholera transmission, millions of people worldwide still must address this devastating disease. Cholera research has so far mainly focused on the causative agent, the bacterium Vibrio cholerae, or on disease treatment, but rarely were results from both fields interconnected. Indeed, the treatment of this severe diarrheal disease is mostly accomplished by oral rehydration therapy (ORT), whereby water and electrolytes are replenished. Commonly distributed oral rehydration salts also contain glucose. Here, we analyzed the effects of glucose and alternative carbon sources on the production of virulence determinants in the causative agent of cholera, the bacterium Vibrio cholerae during in vitro experimentation. We demonstrate that virulence gene expression and the production of cholera toxin are enhanced in the presence of glucose or similarly transported sugars in a ToxR-, TcpP- and ToxT-dependent manner. The virulence genes were significantly less expressed if alternative non-PTS carbon sources, including rice-based starch, were utilized. Notably, even though glucose-based ORT is commonly used, field studies indicated that rice-based ORT performs better. We therefore used a spatially explicit epidemiological model to demonstrate that the better performing rice-based ORT could have a significant impact on epidemic progression based on the recent outbreak of cholera in Haiti. Our results strongly support a change of carbon source for the treatment of cholera, especially in epidemic settings.
    Source: École Polytechnique Fédérale de Lausanne (EPFL)
    Library Location Call Number Volume/Issue/Year Availability
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