1,721,006 research outputs found
Oleoylethanolamide in the homeostatic and non-homeostatic control of eating
The goal of the present study is to evaluate the role of OEA as a potential novel pharmacological target for the treatment of obesity and eating disorders, two major health problems worldwide.
OEA’s ability in inducing consistent and sustained food intake suppression in rats and mice, that is mediated by PPAR-α activation, has been well characterized over the last two decades from my laboratory and from other research groups. In fact, it is now well recognized that the pro-satiety effect of OEA is strictly dependent on the involvement of key brain hypothalamic and hindbrain areas.
However, a crucial aspect remained to be fully elucidated, such as the way by which systemically administered OEA can reach the CNS from the periphery and whether it is able to permeate the brain parenchyma.
In this background, circumventricular organs, such as the AP in the brainstem, are attracting a great deal of attention for their possible role in allowing the direct access to the brain for circulating peptides and other peripheral signals. Moreover, previous data showed that the i.p. administration of OEA, strongly activates neurons of the AP and significantly stimulates c-fos transcription in the subpostremal part of the NST, which is the closest sub nucleus to the AP.
Based on these premises, in order to better delineate the mechanism underlying the eating-inhibitory effects of OEA, the aim of chapter II was to investigate the involvement of the AP in mediating OEA hypophagic action.
To this purpose, in collaboration with Prof. Thomas Lutz at University of Zurich, we subjected rats to a surgical ablation of the AP and evaluated the effects of i.p. OEA administration (10 mg kg−1) on food intake, on Fos expression, on OXY immunoreactivity at both PVN and neurohypophysial level and on the expression of DBH within the brainstem and PVN. Further, we aimed to assess the phenotype of neuronal populations activated by OEA in the brainstem of controls and lesioned rats; to this aim, we assessed, also, whether OEA induced Fos expression co-localized with DBH as marker for noradrenergic neurons. Finally, as last step of our study, we investigated PPAR-alpha expression within the AP.
Furthermore, since there are no observations demonstrating the ability of OEA to permeate the brain parenchyma, in the chapter III I aimed to investigate whether systemically administered OEA might directly reach and permeate the CNS through circumventricular organs devoid of a functional BBB, such as the AP and the ME.
To this purpose, in collaboration with Prof. Lutz and Prof Giulio Muccioli at Université Catholique de Louvain, male Wistar rats were sacrificed at different time points (2.5, 5, 15, 30, 60 minutes) after acute administration of OEA (10 mg kg-1, i.p.). Plasma and different brain areas were collected for UPLC-MS/MS quantification of the main NAEs (including OEA, AEA, PEA, SEA, and LEA), and 2-arachidonoyl-glycerol (2-AG). In particular, in order to selectively investigate OEA concentrations within a variety of PPAR-α-expressing cerebral regions, selected brain areas of interest (AP, ME, NST, ventral and dorsal hippocampus (vHipp and dHipp)) were microdissected and used in this study.
Finally, since current knowledge supports a relationship between neurobiological as well as psychological aspects of overeating, in chapter IV I also investigated the OEA’s pro-satiety action in a rat model of BED, which is a prototypical eating-related maladaptive behaviour that may determine fluctuations in body weight and in some instance may cause obesity.
Among the different networks involved in the behavioural effect of OEA, it has been demonstrated that the systemic administration of OEA to obese rodents restores a “normal brain dopaminergic activity”, which resulted dampened by the excess of fat intake. Moreover, evidence suggests that OEA attenuates the effect of stress by dampening the hyperactivity of the HPA axis. Since both the abnormal dopaminergic transmission and the hyperactivation of HPA axis are considered mechanisms underlying the pathophysiology of BED, by acting at both the two deregulated conditions OEA might represent a potential novel pharmacological target for controlling aberrant eating patterns occurring in BED.
Based on these premises, in order to test this hypothesis in collaboration with Prof. Carlo Cifani of University of Camerino we evaluated OEA effects in a BED model in which female rats with a history of intermittent food restriction show binge-like palatable food consumption after a 15-minute exposure to the sight of the palatable food (frustration stress).
In this model, we investigated the anti-bingeing acute effects of OEA (2.5, 5 or 10 mg kg-1, i.p.) on HPF intake and analysed the neurobiological bases of these effects by focusing on the brain pattern of c-Fos expression, on DA release in the shell of the nucleus accumbens (AcbSh), on monoamine concentrations/turnovers in selected brain regions and on both CRF and OXY mRNA in hypothalamic and extra hypothalamic areas
Oleoylethanolamide in the gut-brain axis
Oleoylethanolamide (OEA), a PPAR-α agonist, is a mediator of satiety. After peripheral administration, OEA induces Fos expression and activation in areas of the CNS involved in the control of feeding behavior and energy homeostasis, such as the nucleus of the solitary tract (NST) and in the area postrema (AP) in the brainstem, the hypothalamic paraventricular (PVN), supraoptic (SON) and ventral tuberomammillary (vTMN) nuclei. Moreover, it is known to increase the noradrenergic trasmission in the NST and AP, by increasing the expression of the dopamine-β-hydroxylase (DBH). Visceral ascending fibers were hypothesized to mediate such effects, but recent findings demonstrate that abdominal vagal afferents are not necessary for the anorectic effect of OEA. In fact, OEA is able to decrease food intake both in rats that underwent a subdiaphragmatic vagal deafferentation (SDA), a surgical procedure that eliminates all abdominal vagal afferents but spares about 50% of the vagal efferents, and in SHAM controls. Thus, the aim of the present work was to better elucidate the role of abdominal vagal afferents in mediating OEA's effects on the CNS. To meet this aim, we subjected rats to SDA surgery, using SHAM rats as control. By using immunohistochemistry, Fos and DBH expression patterns were investigated in the NST, in the AP, and in the hypothalamus after OEA administration (10 mg kg -1).
Consistently with the behavioral results, OEA increases Fos expression in the NST and in the AP. Moreover, in these nuclei, SDA did not cause any alteration of DBH expression. In the hypothalamus, in line with the behavioral results, OEA is able to increase Fos expression in the PVN and the vTMN, even though in the latter does not reach statistical significance.
Overall, our findings indicate that vagal afferents are not strictly necessary for the satiety effect of OEA at both behavioral and neurochemical levels
Going Beyond Counting First Authors in Author Co-citation Analysis
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
“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
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
Dispelling the Myths Behind First-author Citation Counts
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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
Author-wise bibliometric analysis based on entropy.</p
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