562 research outputs found

    Deciphering the role of interleukin-22 in metabolic alterations

    Get PDF
    Inflammatory processes and metabolic alterations are supposed to substantially interact. Recently, cumulating reports describe a profound role of interleukin(IL)-22 in this relationship. IL-22 is a particular kind of immune mediator that is produced by certain lymphocyte populations and regulates the function of several tissue cells but not immune cells. So far, IL-22 was known to plays a fundamental role in the elimination of bacterial infections at border surfaces of the body and to protect tissues from damage. This research highlight article arranges the facts regarding the effects of IL-22 in the context of adiposity and metabolic alterations and postulates a new function of the immune system

    Integration of a RSI microstructure sensing package into a Seaglider

    Get PDF
    Seagliders are a type of propeller-less AUV that glide through the water by changing their buoyancy. They have become mainstream collectors of standard oceanographic data (conductivity, temperature, pressure, dissolved oxygen, fluorescence and backscatter) and are increasingly used as trucks to carry a wide variety of hydrographic and bio-geochemical sensors. The extended sensor capability enhances the utility of the gliders for oceanographic observations. Seagliders are designed and optimized for long-term missions (up to 10 months) and deep sea profiling (up to 1000 m). They provide high resolution oceanographic data with very good temporal and spatial density, in near real-time, at a fraction of the cost of ship collected data. These performance parameters are sometimes at odds with the physical dimensions and electrical requirements of the hydrographic and bio-geochemical sensors scientists want installed in gliders. However, as the acceptance of gliders as an integral component of the oceanographic suite of measurement tools grows so do the efforts of sensor vendors to develop products that meet the size, weight and power requirements for successful glider integration. Turbulence microstructure sensors are one measurement system that scientists desired on Seagliders but that until recently did not fit the glider footprint. In collaboration with Rockland Scientific, Inc., a suite of RSI turbulence microstructure sensors was recently integrated into a Seaglider and the system’s performance validated during field tests in Puget Sound near Seattle, WA and in Loch Linnhe on the west coast of Scotland. Ocean turbulence controls the mixing of water masses, biogeochemical fluxes within them, and facilitates ocean-atmosphere gas exchange. As a result, turbulence impacts global ocean circulation, polar ice melt rates, drawdown of atmospheric carbon dioxide and carbon deposition, coastal and deep ocean ecology, commercial fisheries, and the dispersion of pollutants. Turbulent mixing is also recognized as a key parameter in global climate models, used for understanding and predicting future climate change. Seagliders equipped with turbulence microstructure sensors will allow scientists to map the geographical distribution and temporal variability of mixing in the ocean on scales not possible with ship-based measurements. This presentation discusses the technical aspects of the integration of the turbulence sensor suite on a Seaglider with an emphasis on achieving high data quality, while retaining the performance characteristics of the Seaglider. We will also describe applications for this sensor suite, examine the turbulence measurement data already collected by the Seaglider and discuss future deployment plans

    Stability of Imipenem and Cilastatin Sodium in Total Parenteral Nutrient Solution

    Full text link
    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141138/1/jpen0306.pd

    Phytotherapeuthics Affecting the IL-1/IL-17/G-CSF Axis: A Complementary Treatment Option for Hidradenitis Suppurativa?

    Get PDF
    Hidradenitis suppurativa (HS; also designated as acne inversa) is a chronic inflammatory disease characterized by painful skin lesions that occur in the axillary, inguinal, gluteal and perianal areas of the body. These lesions contain recurring deep-seated, inflamed nodules and pus-discharging abscesses and fistulas. Affecting about 1% of the population, this common disease has gained appropriate clinical attention in the last years. Associated with numerous comorbidities including metabolic syndrome, HS is considered a systemic disease that severely impairs the quality of life and shortens life expectancy. Therapeutic options for HS are limited, comprising long-term antibiotic treatment, the surgical removal of affected skin areas, and neutralization of TNF-alpha, the only approved systemic treatment. Novel treatment options are needed to close the therapeutic gap. HS pathogenesis is increasingly better understood. In fact, neutrophilic granulocytes (neutrophils) seem to be decisive for the development of the purulent destructive skin inflammation in HS. Recent findings suggest a key role of the immune mediators IL-1 beta, IL-17A and G-CSF in the migration into and activation of neutrophils in the skin. Although phytomedical drugs display potent immunoregulatory properties and have been suggested as complementary therapy in several chronic disorders, their application in HS has not been considered so far. In this review, we describe the IL-1/IL-17/G-CSF axis and evaluate it as potential target for an integrated phytomedical treatment of HS

    The herbal extract EPs® 7630 increases the antimicrobial airway defense through monocyte-dependent induction of IL-22 in T cells

    Get PDF
    The phytotherapeutic compound EPs® 7630, an extract manufactured from Pelargonium sidoides roots, is frequently used for the treatment of airway infections. Nevertheless, the knowledge of the mode of action of EPs® 7630 is still sparse. Our study aimed at further elucidating the underlying pharmacological mechanisms by focusing on antimicrobial defense mechanisms of EPs® 7630. While investigating the influence of EPs® 7630 on lymphokine production by PBMCs, we found that EPs® 7630 is a novel inducer of IL-22 and IL-17. This cytokine-inducing effect was most pronounced for IL-22 and clearly dose-dependent starting from 1 μg/ml of the extract. Furthermore, EPs® 7630 pretreatment selectively enhanced the IL-22 and IL-17 production capacity of CD3/28-activated PBMCs while strongly limiting the IFN-γ production capacity of innate lymphoid cells. The relevance of EPs® 7630-induced IL-22 production was proven in vitro and in vivo, where IL-22 provoked a strong increase of the antimicrobial protein S100A9 in lung epithelial cells and pulmonary tissue, respectively. A detailed analysis of IL-22 induction modi revealed no direct influence of EPs® 7630 on the basal or anti-CD3/CD28 antibody-induced IL-22 production by CD4+ memory T cells. In fact, EPs® 7630-induced IL-22 production by CD4+ memory T cells was found to be essentially dependent on soluble mediators (IL-1/IL-23) as well as on direct cellular contact with monocytes. In summary, our study reveals a new immune-modulating function of EPs® 7630 that might confer IL-22 and IL-17-induced protection from bacterial airway infection. KEY MESSAGES: EPs® 7630 selectively strengthens IL-22 and IL-17 production of memory T cells. EPs® 7630 limits the IFN-y production capacity of innate lymphoid cells. EPs® 7630-caused IL-22 production by T cells is essentially dependent on monocytes. IL-22 increase antimicrobial proteins (AMPs) in airway epithelium. EPs® 7630 might protect against airway infection by induction of AMP-inducers

    A Chandra ACIS Study of the Young Star Cluster Trumpler 15 in Carina and Correlation with Near-infrared Sources

    Full text link
    Using the highest-resolution X-ray observation of the Trumpler 15 star cluster taken by the Chandra X-ray Observatory, we estimate the total size of its stellar population by comparing the X-ray luminosity function of the detected sources to a calibrator cluster, and identify for the first time a significant fraction (~14%) of its individual members. The highest-resolution near-IR observation of Trumpler 15 (taken by the HAWK-I instrument on the VLT) was found to detect most of our X-ray selected sample of cluster members, with a K-excess disk frequency of 3.8+-0.7%. The near-IR data, X-ray luminosity function, and published spectral types of the brightest members support a cluster age estimate (5-10 Myr) that is older than those for the nearby Trumpler 14 and Trumpler 16 clusters, and suggest that high-mass members may have already exploded as supernovae. The morphology of the inner ~0.7 pc core of the cluster is found to be spherical. However, the outer regions (beyond 2 pc) are elongated, forming an `envelope' of stars that, in projection, appears to connect Trumpler 15 to Trumpler 14; this morphology supports the view that these clusters are physically associated. Clear evidence of mass segregation is seen. This study appears in a Special Issue of the ApJS devoted to the Chandra Carina Complex Project (CCCP), a 1.42 square degree Chandra X-ray survey of the Great Nebula in Carina.Comment: Accepted for the ApJS Special Issue on the Chandra Carina Complex Project (CCCP), scheduled for publication in May 2011. All 16 CCCP Special Issue papers are available at http://cochise.astro.psu.edu/Carina_public/special_issue.html through 2011 at least. 30 pages; 8 figures; 3 table

    A Potential Link to Skin Destruction and Metabolic Alterations

    Get PDF
    Acne inversa (AI; also designated as hidradenitis suppurativa) is a chronic inflammatory disease with still unknown pathogenesis that affects the intertriginous skin of perianal, inguinal, and axillary sites. It leads to painful nodules, abscesses, and fistulas with malodorous secretion and is frequently associated with metabolic alterations. Here, we demonstrate that one of the most highly upregulated molecules in AI lesions is matrix metalloproteinase 8 (MMP8), an enzyme specialized in the degradation of extracellular matrix components and the HDL component apolipoprotein A-I. Granulocytes, which were present in AI lesions, secreted high amounts of MMP8 especially after TNF-α stimulation. Furthermore, activated fibroblasts but not keratinocytes were found to express MMP8. The high lesional MMP8 levels were accompanied by elevated blood levels that positively correlated with TNF-α blood levels and disease severity assessed by Sartorius score, especially with the number of regions with inflammatory nodules/abscesses and fistulas. Additionally, we found a negative correlation between blood MMP8 and HDL- cholesterol levels, suggesting a contributory role of MMP8 in metabolic alterations in AI. In summary, we demonstrate elevated MMP8 levels in AI lesions, suggest their role in skin destruction and metabolic alterations, and recommend the use of MMP8 as blood biomarker for AI disease activity assessment

    Characterization of an Ex Vivo Skin Model for the Assessment of Dexamethasone-Loaded Core Multishell-Nanocarriers

    Get PDF
    Standard experimental set-ups for the assessment of skin penetration are typically performed on skin explants with an intact skin barrier or after a partial mechanical or chemical perturbation of the stratum corneum, but they do not take into account biochemical changes. Among the various pathological alterations in inflamed skin, aberrant serine protease (SP) activity directly affects the biochemical environment in the superficial compartments, which interact with topically applied formulations. It further impacts the skin barrier structure and is a key regulator of inflammatory mediators. Herein, we used short-term cultures of ex vivo human skin treated with trypsin and plasmin as inflammatory stimuli to assess the penetration and biological effects of the anti-inflammatory drug dexamethasone (DXM), encapsulated in core multishell-nanocarriers (CMS-NC), when compared to a standard cream formulation. Despite a high interindividual variability, the combined pretreatment of the skin resulted in an average 2.5-fold increase of the transepidermal water loss and swelling of the epidermis, as assessed by optical coherence tomography, as well as in a moderate increase of a broad spectrum of proinflammatory mediators of clinical relevance. The topical application of DXM-loaded CMS-NC or DXM standard cream revealed an increased penetration into SP-treated skin when compared to untreated control skin with an intact barrier. Both formulations, however, delivered sufficient amounts of DXM to effectively suppress the production of interleukin-6 (IL-6), interleukin-8 (IL-8) and Thymic Stromal Lymphopoietin (TSLP). In conclusion, we suggest that the herein presented ex vivo inflammatory skin model is functional and could improve the selection of promising drug delivery strategies for anti-inflammatory compounds at early stages of development. View Full-Tex
    • …
    corecore