1,721,010 research outputs found
Antidepressant-like effect of clofibrate: a synthetic PPAR-a agonist
No full textClofibrate, a synthetic fibric acid derivative, is clinically used for the treatment of primary hypercholesterolemia, mixed dyslipidemia and hypertriglyceridemia, and acts as agonist of the alpha subtype of peroxisome proliferator-activated receptor (PPAR alpha). PPARα are nuclear receptors that are strongly expressed in many tissues including specific areas of the brain, possess anti-inflammatory and neuroprotective effects, and regulate lipid metabolism (Pistis M. and Melis M., 2010). Recent data from literature (Crupi R. et al., 2013) and our laboratories have reported that the endogenous ligands, like N-palmitoylethanolamide (PEA), exhibits an antidepressant-like profile in rodent behavioural models of depression. Thus, the present study was designed to investigate the antidepressant and anxiolytic potential of clofibrate using the Forced Swim test (FST) and the Social Interaction test (SI) in rats. We found that the sub-chronic treatment with clofibrate (25 mg/Kg), administered 24, 4 and 1 hour before starting the test, significantly decreased immobility time and increased swimming time in the FST with respect to vehicle-treated control group, without influencing the baseline locomotion in the motility test. Social behavior was evaluated by means of the SI test that could provide a measure of anxiety, with time spent in social interactions being usually elevated by anxiolytic drugs. Animals acutely treated with 12,5 and 25 mg/kg (i.p.) of clofibrate significantly decrease the total time spent in social interactions but do not modify the total numbers of contacts with respect to vehicle-treated controls, thus revealing an anxiogenic-like response. Taken together, our results demonstrate an anxiogenic-like effect of clofibrate after acute administration in the SI, in agreement with the notion that several antidepressants show an anxiogenic profile after a single injection, and an antidepressant profile in subchronic regime of treatment in the FST. If clofibrate and fibrate medications will prove to possess an antidepressant-like effect also in chronic treatment, they might constitute an attractive and safe strategy for the management of depressive disorders since they are already in clinical use.
Pistis M. and Melis M., Curr Med Chem. 2010 17:1450-67.
Crupi R. et al., CNS Neurol Disord Drug Targets. 2013 12:989-1001
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS ALPHA AGONISTS ANTIDEPRESSANT-LIKE EFFECT: BEHAVIORAL CHARACTERIZATION IN RATS
No full textDepression is a chronic and recurrent severe mood disorder that affectsa high percentage of the worldwide population. Unfortunately at least 40% of patients do not respond to the treatment. Therefore, considerable effort is invested in the development of alternative therapeutic approaches for the pharmacotherapy of depression. Peroxisome proliferator-activated receptorsalpha (PPAR-α) are widely expressed in the brain andare activated by endogenous ligands likethe fatty acid amides N-palmitoylethanolamide (PEA) and oleoylethanolamide (OEA), which are involved in the regulation of different physiological function such as inflammation and neuroprotection.Only few studies have been published onPPAR-α mediated behavioral effects, whichsuggests that PEA exerts anxiolytic and antidepressant-like effect in mice(Crupi et al., 2013, Yu et al., 2011).Thus, the aim of our study was to characterize the pharmacological profile of endogenous and synthetic PPAR-α agonists as PEA, OEA and clofibrate by motor activity test to evaluate possible motor impairments, the forced swim test (FSI) for the antidepressant activity,the elevated plus maze (EPM)and the social interaction test (SI)for anxiolytic like effects.
The compounds,tested at different doses and regimen(sub-chronically and chronically) significantly decreased immobility time and increased swimming in the FST test as compared to vehicle treated animals. Theseantidepressant-likeeffectswere reverted the acute administration of the specific PPAR-α antagonist MK886 and of the CB1 antagonist/inverse agonist rimonabant, demonstrating an involvementof thePPAR-α receptor but also an entourage effect of the endocannabinoid system.Moreover,none of thePPAR-αagonists injected subchronically, produced anxiolytic or anxiogenic-like behaviors in the EMP test, while an anxiogenicprofile was observed after acute treatment in the SI test, with a reduction of the total time spent in social interactions but an unaltered numbers of contacts.In conclusion, thesedata show that both endogenous and synthetic PPAR-α ligandsproduce antidepressant-like effects in an experimental animal model, an effect that is specifically mediated via PPAR-α activation but that also involve the endocannabinoid system. PPAR-α agonists, and in particular clofibrate that is still prescribed for the treatment of primary hypercholesterolemia, mixed dyslipidemia, and hypertriglyceridemia, deserve further characterization as a new candidate for the pharmacotherapy of depression.
Crupi R. et al. (2013) CNS Neurol Disord Drug Targets;12(7):989-1001.
Yu HL. et al (2011) Pharmacol Rep.;63(3):834-9
Antidepressant-like effect of clofibrate: a synthetic PPAR-α agonist
No full textClofibrate, a synthetic fibric acid derivative, is clinically used for the treatment of primary hypercholesterolemia, mixed dyslipidemia and hypertriglyceridemia, and acts as agonist of the alpha subtype of peroxisome proliferator-activated receptor (PPAR alpha). PPARα are nuclear receptors that are strongly expressed in many tissues including specific areas of the brain, possess anti-inflammatory and neuroprotective effects, and regulate lipid metabolism (Pistis M. and Melis M., 2010). Recent data from literature (Crupi R. et al., 2013) and our laboratories have reported that the endogenous ligands, like N-palmitoylethanolamide (PEA), exhibits an antidepressant-like profile in rodent behavioural models of depression. Thus, the present study was designed to investigate the antidepressant and anxiolytic potential of clofibrate using the Forced Swim test (FST) and the Social Interaction test (SI) in rats. We found that the sub-chronic treatment with clofibrate (25 mg/Kg), administered 24, 4 and 1 hour before starting the test, significantly decreased immobility time and increased swimming time in the FST with respect to vehicle-treated control group, without influencing the baseline locomotion in the motility test. Social behavior was evaluated by means of the SI test that could provide a measure of anxiety, with time spent in social interactions being usually elevated by anxiolytic drugs. Animals acutely treated with 12,5 and 25 mg/kg (i.p.) of clofibrate significantly decrease the total time spent in social interactions but do not modify the total numbers of contacts with respect to vehicle-treated controls, thus revealing an anxiogenic-like response. Taken together, our results demonstrate an anxiogenic-like effect of clofibrate after acute administration in the SI, in agreement with the notion that several antidepressants show an anxiogenic profile after a single injection, and an antidepressant profile in subchronic regime of treatment in the FST. If clofibrate and fibrate medications will prove to possess an antidepressant-like effect also in chronic treatment, they might constitute an attractive and safe strategy for the management of depressive disorders since they are already in clinical use.
Pistis M. and Melis M., Curr Med Chem. 2010 17:1450-67.
Crupi R. et al., CNS Neurol Disord Drug Targets. 2013 12:989-1001
Variations on the Author
Full text link“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
Full text linkWe 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
Epigenetic regulation of endocannbinoid system in Activity-based model of Anorexia nervosa
No full textDispelling the Myths Behind First-author Citation Counts
Full text linkWe 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
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