Usefulness of image guidance in the surgical treatment of petrous apex cholesterol granuloma

The petrous apex is a pyramid-shaped structure, located medial to the inner ear and the intrapetrous segment of the internal carotid artery. Lesions of the petrous apex can be surgically treated through different surgical routes. Because of the important neurovascular structures located inside the temporal bone, anatomical 3D knowledge is paramount. For this reason, image-guided surgery could represent a useful tool. We report the case of a young woman who came to our observation for a trigeminal neuralgia due to a petrous apex cholesterol granuloma. The lesion was treated through the placement of a drainage tube via an infracochlear approach, with the aid of neuronavigation and intraoperative MRI. Preoperative CT scan images and intraoperative MRI images were fused for surgical planning. The accuracy of the neuronavigation system has proved to be good, and the safety of the procedure was enhanced. Therefore, neuronavigation and intraoperative MRI, though not available in all neurootological centres, should be considered useful tools in these challenging procedures

Study of the Quench Propagation and of the Protection System of the COS-theta NED Dipole Prototype

In this report we present our studies of the propagation of the quench in the NED dipole prototype, to derive a preliminary configuration of the protection system of the magnet (quench protection heaters, dump resistors, etc.). The simulations have been performed by using the code QLASA [1]. In this code, the geometry of the magnet is simplified to a series of solenoidal concentric magnets and the evolution of the quench is calculated with the Wilson's approach [2]. An analogous study has been performed with the CERN code QUABER [3],[4], and the results are discussed in section 3

2- and 8-alkynyl-9-ethyladenines: Synthesis and biological activity at human and rat adenosine receptors

The synthesis of a series of 9-ethyladenine derivatives bearing alkynyl chains in 2- or 8-position was undertaken, based on the observation that replacement of the sugar moiety in adenosine derivatives with alkyl groups led to adenosine receptor antagonists. All the synthesized compounds were tested for their affinity at human and rat A1, A2A, and A3 adenosine receptors in binding assays; the activity at the human A2B receptor was determined in adenylyl cyclase experiments. Biological data showed that the 2-alkynyl derivatives possess good affinity and are slightly selective for the human A2A receptor. The same compounds tested on the rat A1 and A2A subtypes showed in general lower affinity for both receptors. On the other hand, the affinity of the 8-alkynyl derivatives at the human A1, A2A, and A2B receptors proved to be lower than that of the corresponding 2-alkynyl derivatives. On the contrary, the affinity of the same compounds for the human A3 receptor was improved, resulting in A3 selectivity. As in the case of the 2-alkynyl-substituted compounds, the 8-alkynyl derivatives showed decreased affinity for rat receptors. However, it is worthwhile to note that the 8-phenylethynyl-9-ethyladenine was the most active compound of the two series (Ki in the nanomolar range) at both the human and rat A3 subtype. Docking experiments of the 2- and 8-phenylethynyl-9-ethyladenines, at a rhodopsin-based homology model, gave a rational explanation of the preference of the human A3 receptor for the 8-substituted compound

New 2,6,9-trisubstituted adenines as adenosine receptor antagonists: a preliminary SAR profile

A new series of 2,6,9-trisubstituted adenines (5–14) have been prepared and evaluated in radioligand binding studies for their affinity at the human A1, A2A and A3 adenosine receptors and in adenylyl cyclase experiments for their potency at the human A2B subtype. From this preliminary study the conclusion can be drawn that introduction of bulky chains at the N6 position of 9-propyladenine significantly increased binding affinity at the human A1 and A3 adenosine receptors, while the presence of a chlorine atom at the 2 position resulted in a not univocal effect, depending on the receptor subtype and/or on the substituent present in the N6 position. However, in all cases, the presence in the 2 position of a chlorine atom favoured the interaction with the A2A subtype. These results demonstrated that, although the synthesized compounds were found to be quite inactive at the human A2B subtype, adenine is a useful template for further development of simplified adenosine receptor antagonists with distinct receptor selectivity profiles

GPR17 receptor modulators and their therapeutic implications: review of recent patents

Introduction: The GPR17 receptor, phylogenetically related to both purinergic P2Y and CysLT receptors, is mainly expressed in the CNS and, in general, in organs that can typically undergo ischemic damage. This receptor is involved in various pathologies including stroke, brain and spinal cord trauma, multiple sclerosis and in all diseases characterized by neuronal and myelin dysfunction. Therefore, there is a strong needed to identify molecules capable of binding specifically to GPR17 receptors. Areas covered: The review provides a summary of patents, published between 2009 and 2018, on chemicals and biologics and their clinical use. In this work, information is reported about the representative structures and biological activity of recently developed GPR17 receptor ligands. Expert opinion: The GPR17 receptor is an enigmatic receptor and an interesting therapeutic target in a variety of brain disorders and demyelinating diseases such as multiple sclerosis, stroke, schizophrenia, and depression. The modulation of this receptor could also be potentially useful in obesity treatment. Unfortunately, so far, there are no compounds under investigation in clinical trials but many researchers and companies are investing in the discovery of future potential GPR17 receptor drugs

Nb3_3Sn conductor development and characterization for NED

The main purpose of Next European Dipole (NED) project is to design and to build an Nb$_{3}$Sn ~ 15 T dipole magnet. Due to budget constraints, NED is mainly focused on superconducting cable development and production. In this work, an update is given on the NED conductor development by Alstom-MSA and SMI, which uses, respectively, Internal-Tin-Diffusion and Powder-In-Tube methods, with the aim of reaching a non-copper critical current density of ~ 3000 A/mm2 at 12 T and 4.2 K. Characterization results, including critical current and magnetization data, are presented and discussed, as well, for conductors already developed by both companies for this project. SMI succeeded to produce a strand with 50 µm diameter filaments and with a critical current of ~ 1400 A at 4.2 K and 12 T, corresponding to a non-copper critical current density of ~ 2500 A/mm2. Cabling trials with this strand were successfully carried out at LBNL

Erratum to: Molecular modelling study of 2-phenylethynyladenosine (PEAdo) derivatives as highly selective A3 adenosine receptor ligands

A series of 2-phenylethynyladenosine (PEAdo) derivatives substituted in the N6- and 4′position was synthesised and the new derivatives were tested at the four human adenosine receptors stably transfected into Chinese hamster ovary (CHO) cells, using radioligand binding studies (A1, A2A, A3) or adenylyl cyclase activity assay (A2B). Binding studies showed that the presence of a phenyl ethynyl group in the 2 position of adenosine favoured the interaction with A3 receptors, resulting in compounds endowed with high affinity and selectivity for the A3 subtype. Additional substitution of the N6- and 4′position increases both A3 affinity and selectivity. The results showed that the new compounds have a good affinity for the A3 receptor and in particular, the N6-methoxy-2-phenylethynyl-5′N-methylcarboxamidoadenosine, with a Ki at A3 of 1.9 nM and a selectivity A1/A3 and A2A/A3 of 4,800- and 8,600-fold, respectively. Therefore, it is one of the most potent and selective agonists at the human A3 adenosine receptor subtype reported so far. Furthermore, functional assays of inhibition of 10 μM forskolin-stimulated cAMP production via the adenosine A3 receptor revealed that the new trisubstituted adenosine derivatives behave as full agonist of this receptor subtype. Docking analysis of these compounds was performed at a homology model of the human A3 receptor based on the bovine rhodopsin crystal structure as template, and the results are in accordance with the biological data

Adenosine receptor agonists: Synthesis and binding affinity of 2-(aryl)alkylthioadenosine derivatives

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