Molecular Structures of Quiescently Grown and Brain-Derived Polymorphic Fibrils of the Alzheimer Amyloid Aβ9-40 Peptide: A Comparison to Agitated Fibrils

The presence of amyloid deposits consisting primarily of Amyloid-β (Aβ) fibril in the brain is a hallmark of Alzheimer's disease (AD). The morphologies of these fibrils are exquisitely sensitive to environmental conditions. Using molecular dynamics simulations combined with data from previously published solid-state NMR experiments, we propose the first atomically detailed structures of two asymmetric polymorphs of the Aβ9-40 peptide fibril. The first corresponds to synthetic fibrils grown under quiescent conditions and the second to fibrils derived from AD patients' brain-extracts. Our core structure in both fibril structures consists of a layered structure in which three cross-β subunits are arranged in six tightly stacked β-sheet layers with an antiparallel hydrophobic-hydrophobic and an antiparallel polar-polar interface. The synthetic and brain-derived structures differ primarily in the side-chain orientation of one β-strand. The presence of a large and continually exposed hydrophobic surface (buried in the symmetric agitated Aβ fibrils) may account for the higher toxicity of the asymmetric fibrils. Our model explains the effects of external perturbations on the fibril lateral architecture as well as the fibrillogenesis inhibiting action of amphiphilic molecules

Assessment of the Antiviral Properties of Recombinant Porcine SP-D against Various Influenza A Viruses In Vitro

The emergence of influenza viruses resistant to existing classes of antiviral drugs raises concern and there is a need for novel antiviral agents that could be used therapeutically or prophylacticaly. Surfactant protein D (SP-D) belongs to the family of C-type lectins which are important effector molecules of the innate immune system with activity against bacteria and viruses, including influenza viruses. In the present study we evaluated the potential of recombinant porcine SP-D as an antiviral agent against influenza A viruses (IAVs) in vitro. To determine the range of antiviral activity, thirty IAVs of the subtypes H1N1, H3N2 and H5N1 that originated from birds, pigs and humans were selected and tested for their sensitivity to recombinant SP-D. Using these viruses it was shown by hemagglutination inhibition assay, that recombinant porcine SP-D was more potent than recombinant human SP-D and that especially higher order oligomeric forms of SP-D had the strongest antiviral activity. Porcine SP-D was active against a broad range of IAV strains and neutralized a variety of H1N1 and H3N2 IAVs, including 2009 pandemic H1N1 viruses. Using tissue sections of ferret and human trachea, we demonstrated that recombinant porcine SP-D prevented attachment of human seasonal H1N1 and H3N2 virus to receptors on epithelial cells of the upper respiratory tract. It was concluded that recombinant porcine SP-D holds promise as a novel antiviral agent against influenza and further development and evaluation in vivo seems warranted

Efficacy and safety of over-the-counter analgesics in the treatment of common cold and flu

Rationale:  Common cold and flu are the most common human illnesses, and over-the-counter (OTC) analgesics are widely used to treat the pain and fever symptoms. Despite the every day use of these analgesic there is little information available in the literature on the efficacy and safety of these medicines in treating colds and flu symptoms. The aim of this review was to determine the safety and efficacy of the analgesics, aspirin, paracetamol and aspirin for the treatment of colds and flu. Methods:  Electronic databases and a personal database were searched and the information retrieved together with information from relevant textbooks has been integrated in the review. Results:  The literature search established that there is relatively little information on the use of analgesics in treating colds and flu and that much of the safety and efficacy data must be related to other pain and fever models. The review establishes that aspirin, paracetamol and ibuprofen are safe in OTC doses and that there is no evidence for any difference between the medicines as regards efficacy and safety for treatment of colds and flu (except in certain cases such as the use of aspirin in feverish children). There is also no evidence that these medicines prolong the course of colds and flu by any effect on the immune system or by reducing fever. Conclusion:  Despite the lack of clinical data on the safety and efficacy of analgesics for the treatment of colds and flu symptoms a case can be made that these medicines are safe and effective for treatment of these common illnesses

Fungal biofilms in human disease

Fungal biofilms are an important clinical problem. A number of factors including the increasing use of indwelling medical devices wider prescription of broad spectrum antibiotics and an aging and more immuno-compromised patient population has combined to create an opportunity for yeasts and moulds to cause infection. It is also becoming increasingly clear that for a number of serious infections the development of a fungal biofilm is important in the pathophysiology of the infection.<p></p> This chapter will discuss the importance of fungal biofilms in different anatomical areas, will try to provide insights into how fungal biofilm infection should be diagnosed and treated and provide an explanation as to why biofilms may be difficult to treat effectively with routine antifungal regimens.<p></p> Finally it will discuss how our current level of knowledge of the development and biology of fungal biofilms may, in future, lead to a wider choice of therapeutic interventions.<p></p&gt