Three-dimensional minimally invasive video-assisted thyroidectomy: preliminary report

Three-dimensional (3D) minimally invasive video-assisted thyroidectomy (MIVAT) was carried out with a 4-mm, 3D 0-degree stereoscopic endoscope. The procedure was applied on 3 patients who underwent total thyroidectomy and data were prospectively collected. Operative time for total thyroidectomy ranged from 72 to 90 minutes. Neither intra-nor post-operative complications were reported during the study. The surgical team noticed a good perception of depth and easy recognising of anatomic structures, especially concerning the upper and lower vascular pedicle, the parathyroids, the superior and inferior laryngeal nerves. Preliminary impression emerging from this study seems to suggest that 3D MIVAT is safe and effective. Future studies with larger case series are required to determine the role of this procedure

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

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

Radioterapia intraoperatoria nei tumori maligni avanzati estesi all’orecchio medio: valutazione da uno studio retrospettivo

Obiettivo dello studio è stato quello di valutare la sicurezza, l’efficacia e i risultati funzionali della radioterapia intraoperatoria (IORT) seguita dalla radioterapia a intensità modulata (IMRT) nel trattamento di tumori maligni avanzati estesi all’orecchio medio. Sono stati inclusi nello studio in modo retrospettivo 13 pazienti consecutive affetti da tumore dell’orecchio esterno esteso all’orecchio medio. Il follow-up è stato in media di 33 mesi (range 6-133). Cinque pazienti (38%) erano di stadio III e 8 pazienti (62%) erano di stadio IV secondo la classificazione dell’Università di Pittsburgh. Una petrosectomia laterale (LTBR) è stata eseguita in tutti i pazienti, la LTBR è stata associata a parotidectomia in 5 (38%) casi e a svuotamento latero-cervicale associato a parotidectomia in 6 (46%) casi. In tutti i casi si è effettuata asportazione della malattia macroscopicamente evidente. Il trattamento chirurgico è stato completato da IORT (12 Gy) e IMRT (50Gy). Chemioterapia adiuvante è stata eseguita in 4 (30%) casi. Test audiometrici pre- e post-operatori sono stati eseguiti per valutare la perdita uditiva. Il tasso di controllo di malattia locale (LC) a 5 anni, di metastasi a distanza (DM) a 5 anni, la sopravvivenza libera da malattia (DFS) e la sopravvivenza globale (OS) a 5 anni sono state calcolate con il metodo di Kaplan-Meyer. Variazioni significative nella conduzione per via ossea sono state osservate dopo trattamento. Una necrosi parziale del lembo di ricostruzione è stata l’unica complicanza precoce osservata in 3(23%) casi, mentre una fistola meningea è stata osservata in un solo caso (7,6%) come complicanza tardiva. Il tasso di LC è stato del 68%. Il tasso di DM è stato del 90%. Il tasso di DFS è stato del 61%. Il tasso di OS è stato del 69%. La IORT seguita dalla IMRT nel trattamento dei tumori maligni avanzati dell’orecchio esterno e medio sembra essere sicuro. Nel nostro studio non sono riportati morti. La IORT può ridurre la dose di radioterapia postoperatoria a livello del tessuto residuo ottenendo la medesima dose a livello della sede del tumore. Non abbiamo osservato alcuna complicanza a livello dell’orecchio esterno residuo, mentre si è notato un peggioramento dell’udito anche a livello neurosensoriale. Sono necessari studi prospettici al fine di confermare quanto da noi osservato