Synthesis and binding properties of novel selective 5-HT3 receptor ligands

This work reports on the synthesis and affinities for the 5-HT3 versus the 5-HT4 receptor of new piperazinyl-substituted thienopyrimidine derivatives 20-45 with a view to identify potent and selective ligands for the 5-HT3 receptor. Some of the new compounds show good affinity for the 5-HT3 receptor and, notably, do not display any affinity for the 5-HT4 receptor. 4-(4-Methyl-1-piperazinyl)-2-methylthio-6,7-dihydro-5H-cyclopenta[4,5] thieno [2,3-d]pyrimidine 31 exhibits the highest affinity for the 5-HT3 receptor (K-i = 33 nM) and behaves as noncompetitive antagonist. (C) 2004 Elsevier Ltd. All rights reserved

Synthesis and Molecular Modelling Studies of New 1,3-Diaryl-5-Oxo-Proline Derivatives as Endothelin Receptor Ligands

The synthesis of seventeen new 1,3-diaryl-5-oxo-proline derivatives as endothelin receptor (ETR) ligands is described. The structural configuration of the new molecules was determined by analyzing selected signals in proton NMR spectra. In vitro binding assays of the human ETA and ETB receptors allowed us to identify compound 31h as a selective ETAR ligand. The molecular docking of the selected compounds and the ETA antagonist atrasentan in the ETAR homology model provided insight into the structural elements required for the affinity and the selectivity of the ETAR subtype

Education for innovation and entrepreneurship in the food system:the Erasmus+ BoostEdu approach and results

Innovation and entrepreneurship are key factors to provide added value for food systems. Based on the findings of the Erasmus+ Strategic Partnership BoostEdu, the objective of this paper is to provide answers to three knowledge gaps: 1) identify the needs for innovation and entrepreneurship (I&E) in the food sector; 2) understand the best way to organize learning; 3) provide flexibility in turbulent times. BoostEdu aimed to provide a platform for continuing education within I&E for food professionals and was carried out through co-creation workshops and the development of an e-learning course. The results of the project in particular during the Covid-19 pandemics, highlighted the need for flexible access to modules that are complementary to other sources and based on a mix of theoretical concepts and practical experiences. The main lessons learned concern the need of co-creation and co-learning processes to identify suitable practices for the use of innovative digital technologies.</p

Appropriatezza clinica e organizzativa degli interventi di tonsillectomia e/o adenoidectomia. Documento d'indirizzo

Printed from http://www.pnlg.it target=NewWindow>www.pnlg.it (November 2004)Consiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7 , Rome / CNR - Consiglio Nazionale delle RichercheSIGLEITItal

The clinical and organisational appropriateness of tonsillectomy and adenoidectomy

Printed from http://www.pnlg.it target=NewWindow>www.pnlg.it (November 2004)Consiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7 , Rome / CNR - Consiglio Nazionale delle RichercheSIGLEITItal

Fate of melatonin orally administered in preterm newborns: Antioxidant performance and basis for neuroprotection

Preterm infants cannot counteract excessive reactive oxygen species (ROS) production due to preterm birth, leading to an excess of lipid peroxidation with malondialdehyde (MDA) production, capable of contributing to brain damage. Melatonin (ME), an endogenous brain hormone, and its metabolites, act as a free radical scavenger against ROS. Unfortunately, preterms have an impaired antioxidant system, resulting in the inability to produce and release ME. This prospective, multicenter, parallel groups, randomized, double-blind, placebo-controlled trial aimed to assess: (i) the endogenous production of ME in very preterm infants (gestational age <= 29 + 6 WE, 28 infants in the ME and 26 in the placebo group); (ii) the exogenous hormone availability and its metabolization to the main metabolite, 6-OH-ME after 15 days of ME oral treatment; (iii) difference of MDA plasma concentration, as peroxidation marker, after treatment. Blood was collected before the first administration (T1) and after 15 days of administration (T2). ME and 6-OH-ME were detected by liquid chromatography tandem mass spectrometry, MDA was measured by liquid chromatograph with fluorescence detection. ME and 6-OH-ME were not detectable in the placebo group at any study time-point. ME was absent in the active group at T1. In contrast, after oral administration, ME and 6-OH-ME resulted highly detectable and the difference between concentrations T2 versus T1 was statistically significant, as well as the difference between treated and placebo groups at T2. MDA levels seemed stable during the 15 days of treatment in both groups. Nevertheless, a trend in the percentage of neonates with reduced MDA concentration at T2/T1 was 48.1% in the ME group versus 38.5% in the placebo group. We demonstrated that very preterm infants are not able to produce endogenous detectable plasma levels of ME during their first days of life. Still, following ME oral administration, appreciable amounts of ME and 6-OH-ME were available. The trend of MDA reduction in the active group requires further clinical trials to fix the dosage, the length of ME therapy and to identify more appropriate indexes to demonstrate, at biological and clinical levels, the antioxidant activity and consequent neuroprotectant potential of ME in very preterm newborns