169,901 research outputs found
La mediazione penale in Italia: il racconto di un'esperienza. Conversazione con Ernesta Bonetti
No full textRitratto dell'esperienza di un mediatore penale, operante presso il Consutorio familiare Alpha di Chieti
Prefazione [La vittima nel "nuovo mondo" della mediazione penale. Profili di un'assenza]
No full textNo abstract availabl
Mediazione ed esecuzione. Uno strumento per rieducare il condannato?
No full textL'indagine verte sugli spazi di mediazione tra condannato e persona offesa in fase esecutiva; verte, altresì, sulla possibilità di creare un mediatore penale, figura ad oggi ignota al sistema nostrano, se non per qualche sporadica iniziativa, promossa da singoli enti
Synthesis and biological properties of C-terminal vinyl ketone pseudotripeptides
No full textThe ubiquitin-proteasome pathway responsible for the turnover of many cellular proteins represents an attractive target in the development of new drug therapies: In particular, modulation of the proteasome activity by specific inhibitors may represent a useful tool for the treatment of tumours. Here, we report synthesis and activity of a new series of oligopseudopeptide analogues bearing a vinyl ketone pharmacophoric unit at the C-terminal position. Some derivatives showed inhibition in the mu M range of the trypsin-like (T-L) active site of the proteasome
The Fascinating Chemistry of α-Haloamides
No full textThe aim of this review is to highlight the rich chemistry of α-haloamides originally mainly used to discover new C−N, C−O and C−S bond forming reactions, and later widely employed in C−C cross-coupling reactions with C(sp3), C(sp2) and C(sp) coupling partners. Radical-mediated transformations of α-haloamides bearing a suitable located unsaturated bond has proven to be a straightforward alternative to access diverse cyclic compounds by means of either radical initiators, transition metal redox catalysis or visible light photoredox catalysis. On the other hand, cycloadditions with α-halohydroxamate-based azaoxyallyl cations have garnered significant attention. Moreover, in view of the important role in life and materials science of difluoroalkylated compounds, a wide range of catalysts has been developed for the efficient incorporation of difluoroacetamido moieties into activated as well as unactivated substrates
Quanto l'organizzazione degli uffici può incidere sui diritti delle parti private? Note sul ragionevole durata e diritto all'accesso ad un tribunale
No full textUna recente sentenza europea (CEDU, Petrella c. Italia, 18 marzo 2021) condanna l'Italia per avere negato accesso alla giustizia penale alla vittima di un reato, per causa dei ritardi di una procura (sei anni!) nella gestione di un fascicolo. Questo è lo spunto per riflettere sul come l'organizzazione degli uffici giudiziari (nei suoi aspetti più pragmatici: orari di accesso, informatizzazione, misure anti Covid-19, ecc.) influisca sul godimento dei diritti processuali delle parti private
C-terminal trans,trans-muconic acid ethyl ester partial retro-inverso pseudopeptides as proteasome inhibitors
No full textThe development of specific inhibitors of the proteasome represents an important opportunity for new drug therapies. The central role of the multicatalytic complex in the intracellular proteolysis mediated by ubiquitin-proteasome pathway goes to discovery many molecules able to selectively inhibits enzymatic active subsites. Now, we report synthesis and activity of a new partial retro-inverso oligopseudopeptide derivatives bearing a trans, transmuconic acid ethyl ester pharmacophoric unit at the C-terminal. Some analogues selectively inhibited in mu M range the caspase-like (C-L) activity in the beta 1 subunit of the proteasome
Synthetic cannabinoid JWH-018 impairs object recognition memory in mice: behavioral and electrophysiological evidence
No full textIntroduction:
JWH-018 (1-pentyl-3-(1-naphthoyl) indole) is a synthetic CB1 and CB2 agonist illegally marketed in 'Spice' and “herbal blend” for its psychoactive effects similar to those produced by Cannabis. In rodents JWH-018 reproduces the typical effects of THC as hypothermia, analgesia, hypolocomotion and akinesia, while its effects on memory functions are still unknowns. Behavioral and in vitro electrophysiological studies were undertaken to investigated the effects of acute JWH-018 administration on novel object recognition memory and hippocampal LTP formation in CD-1 male mice.
Methods and Results:
The novel object recognition task is a one-trial learning paradigm allowing the assessment of acquisition, consolidation or retrieval of (object) information separately. JWH-018 (0.1-1 mg/Kg i.p.) dose-dependently impaired both short (2 hours after training section) and long (24 hours after training section) memory retention in mice by CB1 receptor stimulation, since JWH-018 effect was prevented by the selective CB-1 receptor antagonist AM251 (3 mg/Kg).
Electrically evoked Schaffer area fEPSP has been extracellularly recorded from stratum radiatum of mouse dorsal hippocampal transversal slices. A stimulus–response curve was recorded before and after JWH-018 contact. At this time, an LTP stimulation paradigm was applied. JWH-018 (10-1000 nM) dose-dependently reduced LTP in hippocampal slices and abolished it at higher concentrations (300 and 1000 nM).
Conclusion:
These results show that JWH-018 impairs cognitive function in mice possibly by impairing hippocampal memory formation. This aspect should be carefully investigated since chronic consumption of THC impairs cognitive function not only in animal models but in particular in human consumers by altering brain neurodevelopment (http://www.dronet.org/monografia.php?monografie=93)
1-Benzyl-N-[3-[spiroisobenzofuran-1(3H),4′-piperidin-1-yl]propyl]pyrrolidine-2-carboxamide (Compound 24) antagonizes NOP receptor-mediated potassium channel activation in rat periaqueductal gray slices
No full textNociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor, the fourth member of opioid receptor family, shares 60-70% homology with traditional opioid receptors but displays little affinity for opioids. This receptor was implicated in many neurological functions and its functional heterogeneity has been proposed. Therefore, it is imperative to develop and characterize new ligands for NOP receptors. 1-Benzyl-N-[3-[spiroisobenzofuran-1(3H),4′-piperidin-1-yl]propyl]pyrrolidine-2-carboxamide (Compound 24) is a new non-peptide ligand of NOP receptor having antagonistic actions in cloned and peripheral NOP receptors. In this study, we quantitatively characterized its effect on the native NOP receptors in the midbrain slices containing ventrolateral periaqueductal gray (vlPAG), a region with dense NOP receptors and involved in pain regulation. In vlPAG neurons, N/OFQ induced G-protein-coupled inwardly rectifying potassium (GIRK) current through NOP receptors. Compound 24, at 0.3-10 μM, attenuated N/OFQ-induced GIRK current concentration-dependently. The antagonistic potency of Compound 24 in vlPAG neurons (IC50: 2.6 ± 0.6 μM) was, however, lower than that obtained in mouse vas deferens preparations or expressed human NOP receptors. The action kinetic of Compound 24 was slower than [Nphe1, Arg14, Lys15]N/OFQ-NH2 (UFP-101), a peptide antagonist, in the same preparation. Compound 24 had no intrinsic agonistic activity at NOP receptors at the concentration up to 10 μM. However, at concentrations higher than 3 μM, it also attenuated the GIRK current induced by [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin, a mu-opioid receptor agonist. It is concluded that Compound 24 acts as a pure antagonist at the native NOP receptors in the vlPAG with moderate potency and selectivity. © 2009 Elsevier B.V. All rights reserved
Modulation of Silent and Constitutively Active Nociceptin/Orphanin FQ Receptors by Potent Receptor Antagonists and Na+ Ions in Rat Sympathetic Neurons
No full textThe pharmacology of G protein-coupled receptors can be influenced by factors such as constitutive receptor activation and Na(+) ions. In this study, we examined the coupling of natively and heterologously expressed nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptors with voltage-dependent Ca(2+) channels following exposure to four high affinity NOP receptor blockers (UFP-101, Trap-101, Comp 24 and JTC-801) in sympathetic neurons. The enhanced tonic inhibition of Ca(2+) currents in the absence of agonists, indicative of constitutively active NOP receptors in transfected neurons, was abolished following pretreatment with pertussis toxin. In control neurons, the four antagonists did not exert any effects when applied alone, but significantly blocked the N/OFQ-mediated Ca(2+) current inhibition. Exposure of transfected neurons to UFP-101 resulted in partial agonist effects. In contrast, Trap-101, Comp 24 and JTC-801 exerted inverse agonism as measured by the loss of tonic Ca(2+) current inhibition. In experiments designed to measure the N/OFQ concentration-response relationship under varying Na(+) concentrations, a leftward shift of IC(50) values was observed after Na(+) exposure. Although similar N/OFQ efficacies were measured with all solutions, a significant decrease of Hill coefficient values was obtained with increasing Na(+) concentrations. Examination of the allosteric effects of Na(+) on heterologously overexpressed NOP receptors showed that the tonic Ca(2+) current inhibition was abolished in the presence of the monovalent cation. These results demonstrate that constitutively active NOP receptors exhibit differential blocker pharmacology and allosteric regulation by Na(+). Data are also presented demonstrating that heterologously expressed mu opioid receptors in sympathetic neurons are similarly modulated
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