Variation of growth characteristics of pneumococcus with environmental conditions.

BACKGROUND: Pneumococcus is exposed to a variety of temperature and oxygen levels in the upper respiratory tract and as it invades the lung, tissues, and blood. We sought to determine the effect of environmental variability on growth in vitro and to assess variability between strains. We evaluated the effect of temperature and oxygen on the growth of 256 isolates representing 53 serotypes, recovered from healthy carriers and disease patients. Strains were grown at a range of temperatures, anaerobically or in ambient air with catalase, and were monitored by reading the optical density. Regression models evaluated variation in the characteristics of the growth curves. RESULTS: Most isolates grew to the maximal density at low temperatures (~33C) and under aerobic conditions. There was considerable variability between strains, and some of this variability was linked to serotype. However, capsule-switch experiments suggest that the production of different capsules might not be sufficient to explain this variation, suggesting there could be interactions between the capsule and genetic background. CONCLUSIONS: Pneumococcal strains vary in how they respond to environmental variations, some of this variation can be explained by the capsule type being produced, but capsule production itself is not sufficient to explain the variability. This variability could help to explain why different lineages of pneumococcus are more common in carriage or disease.

A new paradigm for the treatment of Alzheimer's disease: targeting vascular activation.

No disease-modifying therapies are currently available for Alzheimer's disease (AD), a neurodegenerative disorder that affects more than 36 million people worldwide. Although cardiovascular risk factors such as hypertension and diabetes are increasingly implicated as contributing to the development of AD, the mechanisms whereby these factors influence pathological processes in the AD brain have not been defined. Here we propose, for the first time, vascular activation as a relevant mechanism in AD pathogenesis. We explore this hypothesis in two transgenic AD animal models: AD2576APPSwe (AD2576) and LaFerla 3xTg (3xTgAD) mice using the vascular activation inhibitor sunitinib. Our data show that in both AD animal models, the cerebrovasculature is activated and overexpresses amyloid beta, thrombin, tumor necrosis factor alpha, interleukin-1 beta, interleukin-6, and matrix metalloproteinase 9. Oral administration of sunitinib significantly reduces vascular expression of these proteins. Furthermore, sunitinib improves cognitive function, as assessed by several behavioral paradigms, in both AD animal models. Finally, oxidant injury of brain endothelial cells in culture, resulting in expression of inflammatory proteins, is mitigated by sunitinib. The current data, as well as published studies showing cerebrovascular activation in human AD, support further exploration of vascular-based mechanisms in AD pathogenesis. New thinking about AD pathogenesis and novel, effective treatments are urgently needed. Identification of "vascular activation" as a heretofore unexplored target could stimulate translational investigations in this newly defined area, leading to innovative therapeutic approaches for the treatment of this devastating disease.