1,721,017 research outputs found

    Cannabinoids, immune system and cytokine network

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    How cannabinoids influence immune function has been examined extensively in the last 30 years. Studies on drug-abusing humans and animals, as well as in vitro models employing immune cell cultures, have shown that marijuana, natural and endogenous cannabinoid compounds are immunomodulators. These substances modulate host resistance to bacterial, protozoan and viral infections as well as they can profoundly affect the Th1/Th2 response. Recently, two types of cannabinoid receptor, CB1 and CB2, have been discovered. While CBI is expressed primarily in the brain, CB2 is peculiar of the immune cells. Cannabinoid receptors have been shown to be involved in some but not all of immune effects. Nevertheless, their identification provides a specific mechanism of action in the attempting to find out how exogenous cannabinoids and endogenous cannabinoid system affect the immune apparatus, strengthen the hypothesis of cannabinoids as immunomodulators. As support to this theory, enough evidence exists to suggest that the cannabinoid system significantly affects almost every component of the immune response machinery and impacts the functioning also of the cytokine network. The evaluation of the biological consequences of these drug-induced cytokine changes has also dramatically become important considering not only the impact of cytokines on immune system per se but also envisaging their influence in cancer, inflammation, autoimmune disease, brain injury, hematopoictic colony formation in which cannabinoids have demonstrated a clear role as important modulators

    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

    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

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    PK/PD of flumequine in pigs after intravenous and intramuscular administration

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    Flumequine is a second generation antibacterial quinolone derivative, developed solely for use in animals. The drug is widely employed in food-producing species (ruminants, pigs, birds, fish) to control infections caused by a range of Gram-negative bacteria and is commonly administered at doses of 5-6 up to 15 mg.kg-1 b.w. every 12 hours. The kinetic behavior of flumequine has been studied in many animal species but not in pigs and dosing in these animals are to some extent empirical as it is based on results obtained in other animals. In this study the pharmacokinetics and intramuscular bioavailability of flumequine (15 mg.kg-1) in pigs were determined and the findings related to published minimal inhibitory concentrations (MICs) for susceptible bacteria of animal origin and to experimentally determined MICs for susceptible strains of porcine origin. We determined MICs for Escherichia coli, Salmonella spp., Pasteurella spp. and Bordetella spp isolated from infected pigs in the Forlì area of Italy; Pasteurella multocida strains were particularly sensitive (MIC90 = 0.5 μg.mL-1). After intravenous injection flumequine was slowly distributed and eliminated (t1⁄211.40±0.16 h and t1⁄226.35±1.69 h). The distribution volume at steady state (Vdss) was 752.59±84.03 mL.kg-1 and clearance (ClB) was 237.19±17.88 mL.kg-1.h-1. The bioavailability was about 85%. The PK/PD analysis allows to conclude that flumequine could be effective in controlling respiratory infections caused by Pasteurella multocida, while its effectiveness against gastrointestinal infections caused by Salmonella typhimurium and Escherichia coli may be impaired by the emergence of less sensitive or resistant strains

    Cannabinoids as potential new therapy for the treatment of gliomas.

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    Gliomas constitute the most frequent and malignant primary brain tumors. Current standard therapeutic strategies (surgery, radiotherapy and chemotherapeutics, e.g., temozolomide, carmustin or carboplatin) for their treatment are only palliative and survival diagnosis is normally 6-12 months. The development of new therapeutic strategies for the management of gliomas is therefore essential. Interestingly, cannabinoids have been shown to exert antiproliferative effects on a wide spectrum of cells in culture. Of interest, cannabinoids have displayed a great potency in reducing glioma tumor growth either in vitro or in animal experimental models, curbing the growth of xenografts generated by subcutaneous or intratecal injection of glioma cells in immune-deficient mice. Moreover, cannabinoids appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of nontransformed counterparts. A pilot clinical trial on patients with glioblastoma multiforme demonstrated their good safety profile together and remarkable antitumor effects, and may set the basis for further studies aimed at better evaluating the potential anticancer activity of cannabinoids

    Cannabidiol, a non-psychoactive cannabinoid compound, affects metalloproteinases and pro-survival intracellular pathways in u87-mg human glioma cell line

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    Malignant gliomas are the most common primary brain tumors characterized by a high ability to invade the surrounding brain parenchyma as leading cause of tumor recurrence and treatment failure. Recently, we have shown that the non-psychoactive cannabinoid compound cannabidiol (CBD) induced apoptosis of human glioma cells in vitro and tumor regression in vivo (1, 2). It has been reported that glioma cell migration and invasiveness are hallmarks of gliomas that account in large part for their poor prognosis. To this aim, the first goal of the present study was to investigate the anti-migratory action of CBD by assessing the ability to inhibit U87-MG human glioblastoma cell migration. We found that U87-MG cells exposed to CBD for 16 and 24 h, induced a significant inhibition in the rate of cell motility in scratch wound healing assay. Since among the various factors involved in motility and invasion, matrix metalloproteinases (MMPs) play a pivotal role in promoting tissue breakdown through degradation of extracellular matrix components, we decided to investigate the capability of CBD to interfere with MMPs function. We found that U87-MG cells exposed for 24 h to different concentrations of CBD showed a significant inhibition of MMP-2 release in the supernatants of cell cultures, as evaluated by ELISA assay. CBD also decreased the MMP-2 gelatinolytic activity, as detected by gelatine zymography analysis. Besides, CDB inhibited the expression profile of a set of proteins specifically involved in tumor invasion such as MMP-9, TIMP-1, TIMP-2, TIMP-4, uPa and SerpinE-1. The exposure of U87-MG cells to CBD significantly down-regulated signalling pathways critical for cell survival and proliferation as Akt and Erk. Finally, we tested the effect of CBD on hypoxia-inducible factor HIF-1, one of the most important transcriptional factors involved in tumor invasion and angiogenesis, under experimental conditions mimicking hypoxic state (i.e. exposure to 50 M CoCl2 or 1% pO2 for 24 h). We found that CBD induced a significant decrease of HIF-1 levels under both simulated and actual hypoxic conditions. In conclusion, the present investigation adds further insights into the antitumoral action of the non-psychoactive CBD, showing multiple mechanisms through which the cannabinoid inhibits glioma cell growth and motility. As CBD is a natural compound without psychotropic and side effects, these data lead us to consider CBD as a new potential anticancer drug useful in the management of gliomas
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