17 research outputs found

    Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

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    The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

    Immunization with a Borrelia burgdorferi BB0172-Derived Peptide Protects Mice against Lyme Disease

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    Lyme disease is the most prevalent arthropod borne disease in the US and it is caused by the bacterial spirochete Borrelia burgdorferi (Bb), which is acquired through the bite of an infected Ixodes tick. Vaccine development efforts focused on the von Willebrand factor A domain of the borrelial protein BB0172 from which four peptides (A, B, C and D) were synthesized and conjugated to Keyhole Limpet Hemocyanin, formulated in Titer Max® adjuvant and used to immunize C3H/HeN mice subcutaneously at days 0, 14 and 21. Sera were collected to evaluate antibody responses and some mice were sacrificed for histopathology to evaluate vaccine safety. Twenty-eight days post-priming, protection was evaluated by needle inoculation of half the mice in each group with 103 Bb/mouse, whereas the rest were challenged with 105Bb/mouse. Eight weeks post-priming, another four groups of similarly immunized mice were challenged using infected ticks. In both experiments, twenty-one days post-challenge, the mice were sacrificed to determine antibody responses, bacterial burdens and conduct histopathology. Results showed that only mice immunized with peptide B were protected against challenge with Bb. In addition, compared to the other the treatment groups, peptide B-immunized mice showed very limited inflammation in the heart and joint tissues. Peptide B-specific antibody titers peaked at 8 weeks post-priming and surprisingly, the anti-peptide B antibodies did not cross-react with Bb lysates. These findings strongly suggest that peptide B is a promising candidate for the development of a new DIVA vaccine (Differentiate between Infected and Vaccinated Animals) for protection against Lyme disease.The open access fee for this work was funded through the Texas A&M University Open Access to Knowledge (OAK) Fund

    Individual and environmental factors associated with the seroprevalence of Borrelia burgdorferi

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    Background: Lyme disease (LD) is a common tick-borne disease in Europe. Diverse factors at various scales determine the spatial distribution of Borrelia burgdorferi infection risk and a better understanding of those factors in a spatially explicit framework is needed for disease management and prevention. While the ecology of ticks and the landscape favoring their abundance have been extensively studied, the environmental conditions favoring an intense contact with susceptible humans, including groups at risk, are sparse. The aim of this study is to assess which individual and environmental factors can favor B. burgdorferi infection in a Belgian group professionally at risk. Methods: Serological results of 127 veterinarians and farmers enrolled in this study were analyzed, taking into account their municipality of residence. Using binary logistic regression and considering interaction terms, the joint effects of landscape composition and configuration, and forest and wildlife management were examined. Results: Seven of the 127 workers were seropositive for LD, leading to a seroprevalence of 5.51%. Seropositivity was higher in older persons. The proportion of forest and semi-natural habitats and wetland had a positive impact on LD seroprevalence while arable land–grassland ecotones had a negative one. Our results confirmed the need to consider complex interactions between landscape variables in order to model risk. Conclusions: Our data show that LD has to be considered as a risk for farmers and veterinarians. Rather than focusing either on ecological aspects of tick and pathogen distribution or on purely epidemiological aspects such as individual risk factors, our model highlights the role of human–environment interactions in LD risk assessment
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