1,720,965 research outputs found

    Pharmacokinetics and distribution of clioquinol in golden hamsters

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    Clioquinol (5-chloro-7-iodo-8-quinolinol) is a zinc and copper chelator that can dissolve amyloid deposits and may be beneficial in Alzheimer's disease. Prion diseases are also degenerative CNS disorders characterised by amyloid deposits. The pharmacokinetics and tissue distribution of drugs active against prions may clarify their targets of action. We describe the pharmacokinetics of clioquinol in hamster plasma, spleen and brain after single and repeated oral or intraperitoneal administration (50 mg kg(-1)), as well as after administration with the diet. A single intraperitoneal administration led to peak plasma clioquinol concentrations after 15 min (Tmax), followed by a decay with an apparent half-life of 2.20 +/- 1.1 h. After oral administration, Tmax was reached after 30 min and was followed by a similar process of decay; the AUC(0-last) was 16% that recorded after intraperitoneal administration. The Cmax and AUC values in spleen after a single administration were about 65% (i.p.) and 25% (p.o.) those observed in blood; those in liver were 35% (p.o.) those observed in blood and those in brain were 20% (i.p.) and 10% (p.o.) those observed in plasma. After repeated oral doses, the plasma, brain and spleen concentrations were similar to those observed at the same times after a single dose. One hour after intraperitoneal dosing, clioquinol was also found in the ventricular CSF. Clioquinol was also given with the diet; its morning and afternoon concentrations were similar, and matched those after oral administration. No toxicity was found after chronic administration. Our results indicate that clioquinol, after oral administration with the diet, reaches concentrations in brain and peripheral tissues (particularly spleen) that can be considered effective in preventing prion accumulation, but are at least ten times lower than those likely to cause toxicity

    Effects of protected fish oil in the diet of periparturient dairy goats on phenotypic variation in blood and milk leukocytes

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    The goal of this study was to evaluate the effects of dietary protected fish oil (FO) on phenotypic variation in blood, milk leukocytes, and some productive and metabolic parameters in periparturient dairy goats. About 12 Alpine goats, selected from a larger group of second-parity animals, were fed from 15 days before kidding until the 15th day of lactation with the same basal diet that had been supplemented with either 47 g/head per day of FO or 47 g/head per day hydrogenated palm oil (PO). Dry matter intake, live body weight (LBW), body condition score (BCS), and productive performance were evaluated in 2 weeks after kidding. On days 15, 7, and 2 before kidding and days 2, 7, and 15 after kidding, plasma samples were collected for evaluation of alanine aminotransferase, aspartate aminotransferase, non-esterified fatty acids, glucose, beta-hydroxybutyrate, cholesterol, and urea levels. White blood cell and blood leukocyte subsets were counted in whole blood samples on the kidding day, as well as at 1, 4, and 15 days after kidding. In addition, milk somatic cell count, intramammary infection (IMI), and milk leukocyte subsets were evaluated on days 4 and 15 after kidding. No differences were observed in dry matter intake and BCS, while LBW was higher in FO-fed animals. Milk production and composition, plasma metabolites, and liver enzymes were similar in both experimental groups. Blood CD4 positive cells increased constantly (P = 0.05) in FO-fed group, while CD8 and CD14 cell counts significantly increased 4 days after kidding (P < 0.01). Milk leukocyte subsets showed a significant (P < 0.01) decrease in PO-fed group and a nonsignificant increase (P = 0.34) in FO-fed group, despite the presence of coagulase negative staphylococci IMI The results of the productive performance evaluation agreed with those of many other studies, which did not find any significant differences between dairy goats fed diets enriched with FO or PO supplements. The administration of FO to dairy goats in transition appeared to affect the variation in blood leukocytes with a constant increase in CD4- and CD8-positive cells in comparison with a PO fat-supplemented diet

    Changes in sympathetic activity in prion neuroinvasion

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    Prion diseases are neurodegenerative diseases affecting humans and animals in which the infectious agent or prion is PrPres, a protease-resistant conformer of the cell protein PrP. The natural transmission route of prion diseases is peripheral infection, with the lymphoreticular system (LRS) and peripheral nerves being involved in animal models of scrapie neuroinvasion and human prion diseases. To study the effects of PrP neuroinvasion on sympathetic nerve function, we measured plasma catecholamine levels, blood pressure, heart rate and PrP tissue levels in intraperitoneally or intracerebrally infected mice. The results indicate a specific alteration in sympathetic nerve function because the levels of noradrenaline (but not adrenaline) were increased in the animals infected peripherally (but not in those infected intracerebrally), and correlated with increased blood pressure. These findings confirm that prion neuroinvasion uses the sympathetic nervous system to spread from the periphery to the central nervous system after invading the LRS

    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
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