160,959 research outputs found

    EFFECTS OF LORATADINE ON CYTOSOLIC CA2+ LEVELS AND LEUKOTRIENE RELEASE - NOVEL MECHANISMS OF ACTION INDEPENDENT OF THE ANTIHISTAMINE ACTIVITY

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    Loratadine, a non-sedating anti-histamine drug, displays in vitro potential anti-allergic properties not related to its interaction with the histamine H-1 receptor. In a search for the mechanisms of these actions, we have found that loratadine induces an elevation of cytosolic calcium ion, [Ca2+](i), in rat peritoneal macrophages or human platelets. The mechanism of this elevation resides in the ability of loratadine to discharge intracellular Ca2+ stores, similarly to thapsigargin. This in turn brings about the inhibition of [Ca2+](i) rise induced by physiological activators (platelet activating factor and ADP), as well as by thapsigargin. One of the active metabolites of loratadine, descarbo-ethoxy-loratadine, and another anti-histamine, namely terfenadine, exhibit the same effects. In addition, loratadine partially inhibits antigen-induced leukotriene release from human bronchi, but is unable to inhibit the concomitant contraction. We conclude that loratadine can interfere with the mechanisms controlling Ca2+ release, thus inhibiting the cell activation elicited by various agonists through [Ca2+](i) elevation. This might be the mechanism underlying its anti-allergic actions in vitro. Furthermore, loratadine might represent an interesting tool in the study of Ca2+ homeostasis

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    CR4056, a powerful analgesic imidazoline-2 receptor ligand, inhibits the inflammation-induced PKCε phosphorylation and membrane translocation in sensory neurons

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    Background and Purpose: CR4056 is a first-in-class imidazoline-2 (I2) receptor ligand characterized by potent analgesic activity in different experimental animal models of pain. In a recent phase II clinical trial, CR4056 effectively reduced pain in patients with knee osteoarthritis. In the present study, we investigated the effects of CR4056 on PKCε translocation in vitro and on PKCε activation in vivo in dorsal root ganglia (DRG) neurons. Experimental Approach: Effects of CR4056 on bradykinin-induced PKCε translocation were studied in rat sensory neurons by immunocytochemistry. PKCε activation was investigated by immunohistochemistry analysis of DRG from complete Freund's adjuvant-treated animals developing local hyperalgesia. The analgesic activity of CR4056 was tested on the same animals. Key Results: CR4056 inhibited PKCε translocation with very rapid and long-lasting activity. CR4056 decreased hyperalgesia and phospho-PKCε immunoreactivity in the DRG neurons innervating the inflamed paw. The effect of CR4056 on PKCε translocation was blocked by pertussis toxin, implying that the intracellular pathways involved Gi proteins. The inhibition of PKCε translocation by CR4056 was independent of the α2-adrenoeceptor and, surprisingly, was also independent of idazoxan-sensitive I2 binding sites. The I2 agonist 2BFI had no effect alone but potentiated the activity of low concentrations of CR4056. Conclusions and Implications: Our results demonstrate that CR4056 shares the ability to inhibit PKCε translocation with other analgesics. Whether the inhibition of PKCε involves binding to specific subtype(s) of I2 receptors should be further investigated. If so, this would be a new mode of action of a highly specific I2 receptor ligand

    Larry O. Spencer, Conference Author Presentation

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    Gen. Larry O. Spencer, USAF (Ret.), author of Dark Horse: A Journey from the Horseshoe to the Pentago

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Under Sail The Imagination of Jack London, 1902-1907

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    In this second volume of Author Under Sail Jay Williams investigates the life of Jack London as a professional writer at the turn of the 1900s, as his publications spanned The Call of the Wild to The Iron Heel and The Road. While documenting key life events, especially his rising fame, this biography explores London's necessity to illustrate the inner workings of his own vast imagination through his socialist essays and fiction.Cover -- Title Page -- Copyright Page -- Contents -- Acknowledgments -- Introduction -- 1. Howl, O Heav'nly Muse! -- 2. Jesus in the Theater of Socialism -- 3. Jack London's Place in American Literature -- 4. Theater of War, Theater at Home -- 5. Revolution, Evolution, and the Scene of Writing -- 6. The Jack London Show Goes on the Road -- 7. Red Atavisms and Revolution -- 8. Earthquake Apocalypse and Building the City, Boat, and House Beautiful -- 9. The Future of Socialism and the Death of the Individual -- 10. The Road Never Ends -- Notes -- Bibliography -- IndexIn this second volume of Author Under Sail Jay Williams investigates the life of Jack London as a professional writer at the turn of the 1900s, as his publications spanned The Call of the Wild to The Iron Heel and The Road. While documenting key life events, especially his rising fame, this biography explores London's necessity to illustrate the inner workings of his own vast imagination through his socialist essays and fiction.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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