1,721,124 research outputs found
SYNTHESIS AND PHARMACOLOGICAL CHARACTERIZATION OF RIBOSE-MODIFIED ADENOSINE DERIVATIVES AS P1 RECEPTOR LIGANDS
No full textAdenosine, the natural ligand of P1 receptors, is implicated in the control of many physiological and pathological conditions such as inflammation, pain, cardiovascular and central nervous system (CNS) diseases.1
P1 receptors belong to the large family of GPCR receptors and are divided in four subtypes: A1, A2A, A2B and A3 adenosine receptors (ARs). Even though a large number of P1 ligands have been synthesized and characterized byin vitro and in vivo pharmacological studies, only very few of them are commercially available.
Modifications at the ribose moiety and substitution at the N6-position of adenosine, lead to adenosine derivatives endowed with increased potency at A1 or A3AR. Our previous SAR studies showed that the replacement of OH at 5’-position of the ribose moiety of N6-substituted adenosine derivatives by a chlorine improved A1AR potency and selectivity versus A3AR, with 5′-chloro-5′-deoxy-N6-(±)-(endo- norborn-2-yl)-adenosine (5′Cl5′d-(±)-ENBA) as one of the most potent and selective A1AR agonists,2 while a 5’-C-ethyl-tetrazolyl moiety maintained the A1AR potency, but restored high A3AR affinity, leading to very potent dual A1AR and A3AR ligands.3 Interestingly, both modifications at 5’-position of adenosine derivatives brought to human A3AR antagonism.
In order to further explore the structural determinants of this class of P1 ligands, a new series of ribose- modified N6-substituted adenosine derivatives was synthesized and their pharmacological profile was assayed. The results of this study will be discussed.References
1. Jacobson KA, Muller CE, Neuropharmacology 2015, doi: 10.1016/J.neuropharm.2015.12.001.
2. (a) Franchetti, P.; Cappellacci, L.; Vita, P.; Petrelli, R.; Lavecchia, A.; Kachler, S.; Klotz, K.-N.; Marabese, I.; Luongo, L.; Maione, S.; Grifantini, M. J. Med. Chem. 2009, 52, 2393−2406. (b) Luongo, L.; Petrelli, R.; Gatta, L.; Giordano, C.; Guida, F.; Vita, P.; Franchetti, P.; Grifantini, M.; De Novellis, V.; Cappellacci, L.; Maione, S. Molecules 2012, 17, 13712−13726. (c) Luongo, L.; Guida, F.; Imperatore, R.; Napolitano, F.; Gatta, L.; Cristino, L.; Giordano, C.; Siniscalco, D.; Di Marzo, V.; Bellini, G.; Petrelli, R.; Cappellacci, L.; Usiello, A.; de Novellis, V.; Rossi, F.; Maione, S. Glia 2014, 62, 122−132.
3. Petrelli, R.; Torquati, I.; Kachler, S.; Luongo, L.; Maione, S.; Franchetti, P.; Grifantini, M.; Novellino, E.; Lavecchia, A.; Klotz, K.-N-; Cappellacci, L. J. Med. Chem. 2015, 58, 2560-2566
Effects of 5'-chloro-5'-deoxy-N6-(±)-endo-norbornyl-adenosine, a potent and highly selective A1 adenosine receptor agonist, on neuropathic pain-induced behavioural and morphological changes in spinal microglia
No full textThis study was undertaken in order to investigate the effect of chronic treatment with 5'-chloro-5'-deoxy-N6-(±)-endo-norbornyladenosine (5'Cl5'd-(±)-ENBA),1 a potent and highly selective adenosine A1 receptor agonist, on thermal hyperalgesia and mechanical allodynia in a mouse model of neuropathic pain, the spared nerve injury (SNI). Chronic systemic administrations of 5'Cl5'd-(±)-ENBA (0.5 mg/kg, i.p once a day) reduced both thermal hyperalgesia and mechanical allodynia 3 and 7 days after SNI, in a way prevented by DPCPX (3 mg/kg, i.p.), a selective A1 receptor antagonist. SNI induced spinal changes on microglial activation ipsilaterally to the nerve injury. Moreover, 5'Cl5'd-(±)-ENBA significantly reduced microglial activation in vitro. In particular pre-incubation with 5'Cl5'd-(±)-ENBA prevented the microglial morphological changes induced by LPS, ATP, LPS+ATP challenges. Our results demonstrated an involvement of A1 receptors in the increase of nociceptive thresholds and in spinal changes occurred in neuropathic pain. In addition, 5'Cl5'd-(±)-ENBA antiallodynic and antihyperalgesic effects could be mediated by the A1 receptors expressed on microglial cells.
(1) Franchetti, P.; Cappellacci, L.; Vita, P.; Petrelli, R.; Lavecchia, A.; Kachler, S.; Klotz, K.-N.; Marabese, I.; Luongo, L.; Maione, S.; Grifantini, M. J. Med. Chem. 2009, 52, 2393-2406
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
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
MORFOGENESI E ATTIVITÀ PROLIFERATIVA NEL SISTEMA OLFATTIVO DI XENOPUS LAEVIS E RANA ESCULENTA
No full textDevelopmental analysis of the extrabulbar olfactory projections in the ranid frog with some phylogenetic considerations
No full textThis study has examined the presence and distribution of extrabulbar olfactory projections (nerve fibers that originate from cells in the olfactory epithelium, bypass the olfactory bulbs and project caudally into the brain) in larvae and adult stages of a semi-aquatic frog, Rana esculenta. This species was chosen because previous work had suggested that the presence of an extrabulbar olfactory system (EBOS) may correlate with the detection of water-borne odorants. The main result is that this extrabulbar system is present in both larval and adult specimens of this frog species. In stage 26, the earliest one used in our study, the EBOS is well-developed and projects as far caudal as the rhombencephalon. During successive larval development and until the completion of metamorphosis, there occurs a progressive reduction in the caudal extent of the EBOS. This reduction is more dramatic during the metamorphic climax (stages 31-33). A reduction in the caudal extent of the extrabulbar projections in adult stages is similar to other species previously examined. We are inclined to believe that there is no correlation between a reduction in the caudal extent of the EBOS and transition from water to land
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