[Not Available].

Objectives: To assess the safety profile of dietary supplements with a focus on those purchased online or reported via the internet.

Results: Among the 2,367 reports of Adverse Reactions (ARs) to dietary supplements collected within the Italian Phitovigilance System, 49.4% were from citizens and 33.

Analysis of suspected adverse reactions to food supplements containing beehive products: an update from the Italian Phytovigilance System.

Introduction: Beehive products are widely used in food supplements; however, their composition variability and allergenic components have raised some concerns. This work aims to provide information about the beehive products safety profile by evaluating the suspected adverse reactions (ARs).

Methods: The suspected report of ARs collected within the Italian Phytovigilance System (IPS) were evaluated.

Design of Analgesic Trivalent Peptides with Low Withdrawal Symptoms: Probing the Antinociceptive Profile of Novel Linear and Cyclic Peptides as Opioid Pan Ligands.

The discovery of efficacious and safe analgesics with reduced side effects is the foremost challenge in the pain field. In this work, we report the and evaluation of linear and cyclic analogues of biphalin with the aim to complete the series of structural modifications previously applied in the development of opioid peptides incorporating a xylene bridge. Replacement of Tyr by Dmt (2,5-dimethyltyrosine) in the linear biphalin analogue and cyclic analogue resulted in two new compounds (namely, and ) endowed with improved KOR/MOR/DOR binding affinity.

Discovery of κ Opioid Receptor (KOR)-Selective d-Tetrapeptides with Improved Antinociceptive Effect after Peripheral Administration.

Peripherally active tetrapeptides as selective κ opioid receptor (KOR) agonists have been prepared in good overall yields and high purity following solid-phase peptide synthesis via Fmoc protection strategy. Structural modifications at the first and second position of the FF(d-Nle)R-NH () were contemplated with aromatic side chains containing d-amino acids, such as (d)-F-Phe, (d)-F-Phe, (d)-F-Phe, which led to highly selective and efficacious KOR agonists endowed with strong antinociceptive activity following intravenous (i.v.

In Silico Identification of Tripeptides as Lead Compounds for the Design of KOR Ligands.

The kappa opioid receptor (KOR) represents an attractive target for the development of drugs as potential antidepressants, anxiolytics and analgesics. A robust computational approach may guarantee a reduction in costs in the initial stages of drug discovery, novelty and accurate results. In this work, a virtual screening workflow of a library consisting of ~6 million molecules was set up, with the aim to find potential lead compounds that could manifest activity on the KOR.

Selective MOR activity of DAPEA and Endomorphin-2 analogues containing a (R)-γ-Freidinger lactam in position two.

The use of α-amino-γ lactam of Freidinger (Agl) may serve as an impressive method to increase the biological stability of peptides and an appropriate tool to elucidate their structure-activity relationships. The endomorphin-2 (EM-2) and [D-Ala, des-Leu] enkephalin amide (DAPEA) are two linear opioid tetrapeptides agonists of MOR and MOR/DOR respectively. Herein, we investigated the influence of the incorporation of (R/S)-Agl in position 2 and 3 on the biological profile of the aforementioned products in vitro and in vivo.

Discovery of Orexant and Anorexant Agents with Indazole Scaffold Endowed with Peripheral Antiedema Activity.

The endocannabinoid system represents an integrated neuronal network involved in the control of several organisms' functions, such as feeding behavior. A series of hybrids of 5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl--(piperidin-1-yl)-1-pyrazole-3-carboxamide (mimonabant), a well-known inverse agonist of the type-1 cannabinoid receptor (CB1), once used as an antiobesity drug, and the -(2)-substitutes of 1-[(4-fluorophenyl)methyl]indazole-3-carboxamide with 1-amino-3-methyl-1-oxobutane (AB-Fubinaca), 1-amino-3,3-dimethyl-1-oxobutane (ADB-Fubinaca), and 3-methylbutanoate (AMB-Fubinaca), endowed with potent agonistic activity towards cannabinoid receptors CB1 and CB2 were in solution as -terminal amides, acids, methyl esters and -methyl amides. These compounds have been studied by binding assays to cannabinoid receptors and by functional receptor assays, using rat brain membranes in vitro.

Novel Cyclic Biphalin Analogues by Ruthenium-Catalyzed Ring Closing Metathesis: and Biological Profile.

In this work we report the application of the ring-closing metathesis (RCM) to the preparation of two cyclic olefin-bridged analogues of biphalin (Tyr-d-Ala-Gly-Phe-NH-NH ← Phe ← Gly ← d-Ala ← Tyr), using the second generation Grubbs' catalyst. The resulting - and -cyclic isomers were identified, fully characterized, and tested at μ (ΜΟR), δ (DOR), and κ (KOR) opioid receptors and for antinociceptive activity. Both were shown to be full agonists at MOR and potential partial antagonists at DOR, with low potency KOR agonism.

On resin click-chemistry-mediated synthesis of novel enkephalin analogues with potent anti-nociceptive activity.

Here, we report the chemical synthesis of two DPDPE analogues 7a (NOVA1) and 7b (NOVA2). This entailed the solid-phase synthesis of two enkephalin precursor chains followed by a Cu-catalyzed azide-alkyne cycloaddition, with the aim of improving in vivo analgesic efficacy versus DPDPE. NOVA2 showed good affinity and selectivity for the μ-opioid receptor (K of 59.

Amyotrophic Lateral Sclerosis and soccer: an internet survey of 29 Italian players.

Objectives: Previous epidemiological studies reported a significantly higher risk of Amyotrophic Lateral Sclerosis (ALS) in Italian male soccer players. As a consequence, sports newspapers and news agencies focused on this issue and spread the news of 51 male soccer players with a reported diagnosis of ALS.

Design: We searched news on male Italian national soccer players with a reported diagnosis of ALS quoted from January 1, 1950 to July 31, 2016 in at least two Internet web sites or in books by journalists.

Lignans and secoiridoid glycosides from the stem barks of Jasminum tortuosum.

This paper reports on the first phytochemical analysis ever performed on Jasminum tortuosum Willd. This analysis, mainly carried out by means of column chromatography separation, NMR spectroscopy and mass spectrometry, led to the isolation and the identification of four compounds, namely the lignans ginkgool (1) and olivil-4'-O-β-glucopyranoside (2) and the secoiridoids oleoside dimethyl ester (3) and oleoside 11-methyl ester (4). The presence of these compounds is significant from a chemotaxonomic point of view, confirming the correct botanical classification of the species and, from a phytochemical standpoint, may suggest its possible use in the ethno-medicinal field.