Testing the vagal withdrawal hypothesis during light exercise under autonomic blockade: a heart rate variability study

Introduction. We performed the first analysis of heart rate variability (HRV) at rest and exercise under full autonomic blockade on the same subjects, to test the conjecture that vagal tone withdrawal occurs at exercise onset. We hypothesized that, between rest and exercise: i) no differences in total power (PTOT) under parasympathetic blockade; ii) a PTOT fall under β1-sympathetic blockade; iii) no differences in PTOT under blockade of both ANS branches. Methods. 7 males (24±3 years) performed 5-min cycling (80W) supine, preceded by 5-min rest during control and with administration of atropine, metoprolol and atropine+metoprolol (double blockade). Heart rate and arterial blood pressure were continuously recorded. HRV and blood pressure variability were determined by power spectral analysis, and baroreflex sensitivity (BRS) by the sequence method. Results. At rest, PTOT and the powers of low (LF) and high (HF) frequency components of HRV were dramatically decreased in atropine and double blockade compared to control and metoprolol, with no effects on LF/HF ratio and on the normalised LF (LFnu) and HF (HFnu). At exercise, patterns were the same as at rest. Comparing exercise to rest, PTOT varied as hypothesized. For SAP and DAP, resting PTOT was the same in all conditions. At exercise, in all conditions, PTOT was lower than in control. BRS decreased under atropine and double blockade at rest, under control and metoprolol during exercise. Conclusions. The results support the hypothesis that vagal suppression determined disappearance of HRV during exercise

Novel Nanogels Loaded with Mn(II) Chelates as Effective and Biologically Stable MRI Probes

Here it is described nanogels (NG) based on a chitosan matrix, which are covalently stabilized by a bisamide derivative of Mn-t-CDTA (t-CDTA = trans-1,2-diaminocyclohexane-N,N,N & PRIME;,N & PRIME;-tetraacetic acid). the Mn(II) complex acts both as a contrast medium and as a cross-linking agent. These nanogels are proposed as an alternative to the less stable paramagnetic nanogels obtained by electrostatic interactions between the polymeric matrix and paramagnetic Gd(III) chelates. The present novel nanogels show: i) relaxivity values seven times higher than that of typical monohydrated Mn(II) chelates at the clinical fields, thanks to the combination of a restricted mobility of the complex with a fast exchange of the metal-bound water molecule; ii) high stability of the formulation over time at pH 5 and under physiological conditions, thus excluding metal leaking or particles aggregation; iii) good extravasation and accumulation, with a maximum contrast achieved at 24 h post-injection in mice bearing subcutaneous breast cancer tumor; iv) high T-1 contrast (1 T) in the tumor 24 h post-injection. These improved properties pave the way for the use of these paramagnetic nanogels as promising magnetic resonance imaging (MRI) probes for in vitro and in vivo preclinical applications

Standard vs delayed ligature of the dorsal vascular complex during robot-assisted radical prostatectomy: results from a randomized controlled trial

xx

Per un dibattito più critico sull'aiuto medico a morire. Una prospettiva etico-clinica

Riassunto. Il dibattito bioetico sull’aiuto medico a morire si è concentrato finora principalmente sulle ragioni filosofiche pro o contro tale pratica. Meno esplorato è invece un diverso approccio, tipico della bioetica clinica, che si propone di impostare la discussione a partire innanzitutto da una lettura approfondita della realtà socio-culturale e del contesto clinico-assistenziale in cui le domande di aiuto a morire sorgono e vengono affrontate. In questo saggio mi propongo di sviluppare questo approccio, anche con riferimento ad alcune tra le prime esperienze di gestione delle domande di suicidio medicalmente assistito presentate in Italia alle Aziende sanitarie. L’obiettivo è far emergere la complessità e i paradossi entro cui si svolge l’attuale discussione sull’aiuto medico a morire, al fine di offrire spunti di riflessione per un dibattito più critico e consapevole. Toward a more critical debate on physician-assisted death. A clinical ethics perspective. Summary. The bioethical debate on physician-assisted death has so far primarily focused on philosophical arguments for or against this practice. However, there has been limited exploration of an alternative approach, characteristic of clinical bioethics, which sets out to contextualize the discussion within a thorough analysis of the socio-cultural and healthcare environment in which requests to hasten death arise and are handled. This paper aims to develop this approach, taking into account some of the initial experiences in Italy of managing requests for physician-assisted suicide submitted to Local Healthcare Authorities. The goal is to uncover the complexities and paradoxes inherent in the ongoing discussion on physician-assisted death, with the intention of contributing to a more critical and informed debate