11,373 research outputs found

    A Role for Nanoparticles in Treating Traumatic Brain Injury

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    Traumatic brain injury (TBI) is one of the main causes of disability in children and young adults, as well as a significant concern for elderly individuals. Depending on the severity, TBI can have a long-term impact on the quality of life for survivors of all ages. The primary brain injury can result in severe disability or fatality, and secondary brain damage can increase the complexities in cellular, inflammatory, neurochemical, and metabolic changes in the brain, which can last decades post-injury. Thus, survival from a TBI is often accompanied by lifelong disabilities. Despite the significant morbidity, mortality, and economic loss, there are still no eective treatment options demonstrating an improved outcome in a large multi-center Phase III trial, which can be partially attributed to poor target engagement of delivered therapeutics. Thus, there is a significant unmet need to develop more eective delivery strategies to overcome the biological barriers that would otherwise inhibit transport of materials into the brain to prevent the secondary long-term damage associated with TBI. The complex pathology of TBI involving the blood-brain barrier (BBB) has limited the development of eective therapeutics and diagnostics. Therefore, it is of great importance to develop novel strategies to target the BBB. The leaky BBB caused by a TBI may provide opportunities for therapeutic delivery via nanoparticles (NP). The focus of this review is to provide a survey of NP-based strategies employed in preclinical models of TBI and to provide insights for improved NP based diagnostic or treatment approaches. Both passive and active delivery of various NPs for TBI are discussed. Finally, potential therapeutic targets where improved NP-mediated delivery could increase target engagement are identified with the overall goal of providing insight into open opportunities for NP researchers to begin research in TBI

    Dependence receptor involvement in subtilisin-induced long-term depression and in long-term potentiation

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    The serine protease subtilisin induces a form of long-term depression (LTD) which is accompanied by a reduced expression of the axo-dendritic guidance molecule Unco-ordinated-5C (Unc-5C). One objective of the present work was to determine whether a loss of Unc-5C function contributed to subtilisin-induced LTD by using Unc-5C antibodies in combination with the pore-forming agents Triton X-100 (0.005%) or streptolysin O in rat hippocampal slices. In addition we have assessed the effect of subtilisin on the related dependence receptor Deleted in Colorectal Cancer (DCC) and used antibodies to this protein for functional studies. Field excitatory postsynaptic potentials (fEPSPs) were analysed in rat hippocampal slices and protein extracts were used for Western blotting. Subtilisin produced a greater loss of DCC than of Unc-5C, but the antibodies had no effect on resting excitability or fEPSPs and did not modify subtilisin-induced LTD. However, antibodies to DCC but not Unc-5C did reduce the amplitude of theta-burst long-term potentiation (LTP). In addition, two inhibitors of endocytosis – dynasore and tat-gluR2(3Y) – were tested and, although the former compound had no effect on neurophysiological responses, tat-gluR2(3Y) did reduce the amplitude of subtilisin-induced LTD without affecting the expression of DCC or Unc-5C but with some loss of PostSynaptic Density Protein-95. The results support the view that the dependence receptor DCC may be involved in LTP and suggest that the endocytotic removal of a membrane protein or proteins may contribute to subtilisin-induced LTD, although it appears that neither Unc-5C nor DCC are involved in this process. (220)

    A method for developing design diagrams for ceramic and glass materials using fatigue data

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    The service lifetime of glass and ceramic materials can be expressed as a plot of time-to-failure versus applied stress whose plot is parametric in percent probability of failure. This type of plot is called a design diagram. Confidence interval estimates for such plots depend on the type of test that is used to generate the data, on assumptions made concerning the statistical distribution of the test results, and on the type of analysis used. This report outlines the development of design diagrams for glass and ceramic materials in engineering terms using static or dynamic fatigue tests, assuming either no particular statistical distribution of test results or a Weibull distribution and using either median value or homologous ratio analysis of the test results

    Glass transition in Ultrathin Polymer Films : A Thermal Expansion Study

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    Glass transition process gets affected in ultrathin films having thickness comparable to the size of the molecules. We observe systematic broadening of glass transition temperature (Tg) as the thickness of the polymer film reduces below the radius of gyration but the change in the average Tg was found to be very small. Existence of reversible negative and positive thermal expansion below and above Tg increased the sensitivity of our thickness measurements performed using energy dispersive x-ray reflectivity. A simple model of Tg variation as a function of depth expected from sliding motion could explain the results. We observe clear glass transition even for 4 nm polystyrene film that was predicted to be absent from ellipsometry measurements of thicker films.Comment: 11 pages, 5 figure
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