5,405 research outputs found

    Self-assembling nanoparticles containing dexamethasone as a novel therapy in allergic airways inflammation.

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    Nanocarriers can deliver a wide variety of drugs, target them to sites of interest, and protect them from degradation and inactivation by the body. They have the capacity to improve drug action and decrease undesirable systemic effects. We have previously developed a well-defined non-toxic PEG-dendritic block telodendrimer for successful delivery of chemotherapeutics agents and, in these studies, we apply this technology for therapeutic development in asthma. In these proof-of-concept experiments, we hypothesized that dexamethasone contained in self-assembling nanoparticles (Dex-NP) and delivered systemically would target the lung and decrease allergic lung inflammation and airways hyper-responsiveness to a greater degree than equivalent doses of dexamethasone (Dex) alone. We found that ovalbumin (Ova)-exposed mice treated with Dex-NP had significantly fewer total cells (2.78 ± 0.44 × 10(5) (n = 18) vs. 5.98 ± 1.3 × 10(5) (n = 13), P<0.05) and eosinophils (1.09 ± 0.28 × 10(5) (n = 18) vs. 2.94 ± 0.6 × 10(5) (n = 12), p<0.05) in the lung lavage than Ova-exposed mice alone. Also, lower levels of the inflammatory cytokines IL-4 (3.43 ± 1.2 (n = 11) vs. 8.56 ± 2.1 (n = 8) pg/ml, p<0.05) and MCP-1 (13.1 ± 3.6 (n = 8) vs. 28.8 ± 8.7 (n = 10) pg/ml, p<0.05) were found in lungs of the Dex-NP compared to control, and they were not lower in the Dex alone group. In addition, respiratory system resistance was lower in the Dex-NP compared to the other Ova-exposed groups suggesting a better therapeutic effect on airways hyperresponsiveness. Taken together, these findings from early-stage drug development studies suggest that the encapsulation and protection of anti-inflammatory agents such as corticosteroids in nanoparticle formulations can improve efficacy. Further development of novel drugs in nanoparticles is warranted to explore potential treatments for chronic inflammatory diseases such as asthma

    Type 1 diabetes in very young children: a model of parent and child influences on management and outcomes

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135479/1/pedi12351.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135479/2/pedi12351_am.pd

    Obesity Reduction Within a Generation: The Dual Roles of Prevention and Treatment

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93699/1/oby.2011.199.pd

    Special Lagrangian cones with higher genus links

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    For every odd natural number g=2d+1 we prove the existence of a countably infinite family of special Lagrangian cones in C^3 over a closed Riemann surface of genus g, using a geometric PDE gluing method.Comment: 48 page

    A New Method for Searching for Free Fractional Charge Particles in Bulk Matter

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    We present a new experimental method for searching for free fractional charge in bulk matter; this new method derives from the traditional Millikan liquid drop method, but allows the use of much larger drops, 20 to 100 mm in diameter, compared to the traditional method that uses drops less than 15 mm in diameter. These larger drops provide the substantial advantage that it is then much easier to consistently generate drops containing liquid suspensions of powdered meteorites and other special minerals. These materials are of great importance in bulk searches for fractional charge particles that may have been produced in the early universe.Comment: 17 pages, 5 figures in a singl PDF file (created from WORD Doc.). Submitted to Review of Scientific Instrument

    Deletion of astroglial CXCL10 delays clinical onset but does not affect progressive axon loss in a murine autoimmune multiple sclerosis model.

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    Multiple sclerosis (MS) is characterized by central nervous system (CNS) inflammation, demyelination, and axonal degeneration. CXCL10 (IP-10), a chemokine for CXCR3+ T cells, is known to regulate T cell differentiation and migration in the periphery, but effects of CXCL10 produced endogenously in the CNS on immune cell trafficking are unknown. We created floxed cxcl10 mice and crossed them with mice carrying an astrocyte-specific Cre transgene (mGFAPcre) to ablate astroglial CXCL10 synthesis. These mice, and littermate controls, were immunized with myelin oligodendrocyte glycoprotein peptide 35-55 (MOG peptide) to induce experimental autoimmune encephalomyelitis (EAE). In comparison to the control mice, spinal cord CXCL10 mRNA and protein were sharply diminished in the mGFAPcre/CXCL10fl/fl EAE mice, confirming that astroglia are chiefly responsible for EAE-induced CNS CXCL10 synthesis. Astroglial CXCL10 deletion did not significantly alter the overall composition of CD4+ lymphocytes and CD11b+ cells in the acutely inflamed CNS, but did diminish accumulation of CD4+ lymphocytes in the spinal cord perivascular spaces. Furthermore, IBA1+ microglia/macrophage accumulation within the lesions was not affected by CXCL10 deletion. Clinical deficits were milder and acute demyelination was substantially reduced in the astroglial CXCL10-deleted EAE mice, but long-term axon loss was equally severe in the two groups. We concluded that astroglial CXCL10 enhances spinal cord perivascular CD4+ lymphocyte accumulation and acute spinal cord demyelination in MOG peptide EAE, but does not play an important role in progressive axon loss in this MS model

    On the mean-field spherical model

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    Exact solutions are obtained for the mean-field spherical model, with or without an external magnetic field, for any finite or infinite number N of degrees of freedom, both in the microcanonical and in the canonical ensemble. The canonical result allows for an exact discussion of the loci of the Fisher zeros of the canonical partition function. The microcanonical entropy is found to be nonanalytic for arbitrary finite N. The mean-field spherical model of finite size N is shown to be equivalent to a mixed isovector/isotensor sigma-model on a lattice of two sites. Partial equivalence of statistical ensembles is observed for the mean-field spherical model in the thermodynamic limit. A discussion of the topology of certain state space submanifolds yields insights into the relation of these topological quantities to the thermodynamic behavior of the system in the presence of ensemble nonequivalence.Comment: 21 pages, 5 figure

    Can longitudinal generalized estimating equation models distinguish network influence and homophily? An agent-based modeling approach to measurement characteristics

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    Abstract Background Connected individuals (or nodes) in a network are more likely to be similar than two randomly selected nodes due to homophily and/or network influence. Distinguishing between these two influences is an important goal in network analysis, and generalized estimating equation (GEE) analyses of longitudinal dyadic network data are an attractive approach. It is not known to what extent such regressions can accurately extract underlying data generating processes. Therefore our primary objective is to determine to what extent, and under what conditions, does the GEE-approach recreate the actual dynamics in an agent-based model. Methods We generated simulated cohorts with pre-specified network characteristics and attachments in both static and dynamic networks, and we varied the presence of homophily and network influence. We then used statistical regression and examined the GEE model performance in each cohort to determine whether the model was able to detect the presence of homophily and network influence. Results In cohorts with both static and dynamic networks, we find that the GEE models have excellent sensitivity and reasonable specificity for determining the presence or absence of network influence, but little ability to distinguish whether or not homophily is present. Conclusions The GEE models are a valuable tool to examine for the presence of network influence in longitudinal data, but are quite limited with respect to homophily.http://deepblue.lib.umich.edu/bitstream/2027.42/134740/1/12874_2016_Article_274.pd
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