Numerical characterization of intraoperative and chronic electrodes in deep brain stimulation

An intraoperative electrode (microelectrode) is used in the deep bra In stImulation (DBS) technique to pinpoint the brain target and to choose the best parameters for the electrical stimulus. However, when the intraoperative electrode is replaced with the chronic one (macroelectrode), the observed effects do not always coincide with predictions. To investigate the causes of such discrepancies, a 3D model of the basal ganglia has been considered and realistic models of both intraoperative and chronic electrodes have been developed and numerically solved. Results of simulations of the electric potential (V) and the activating function (AF) along neuronal fibers show that the different geometries and sizes of the two electrodes do not change the distributions and polarities of these functions, but rather the amplitudes. This effect is similar to the one produced by the presence of different tissue layers (edema or glial tissue) in the pen-electrode space. Conversely, an inaccurate positioning of the chronic electrode with respect to the intraoperative one (electric centers not coincident) may induce a completely different electric stimulation in some groups of fibers

Restoring the encoding properties of a stochastic neuron model by an exogenous noise

Here we evaluate the possibility of improving the encoding properties of an impaired neuronal system by superimposing an exogenous noise to an external electric stimulation signal. The approach is based on the use of mathematical neuron models consisting of stochastic HH-like circuit, where the impairment of the endogenous presynaptic inputs is described as a subthreshold injected current and the exogenous stimulation signal is a sinusoidal voltage perturbation across the membrane. Our results indicate that a correlated Gaussian noise, added to the sinusoidal signal can significantly increase the encoding properties of the impaired system, through the Stochastic Resonance (SR) phenomenon. These results suggest that an exogenous noise, suitably tailored, could improve the efficacy of those stimulation techniques used in neuronal systems, where the presynaptic sensory neurons are impaired and have to be artificially bypassed

A computational model for real-time calculation of electric field due to transcranial magnetic stimulation in clinics

The aim of this paper is to propose an approach for an accurate and fast (real-time) computation of the electric field induced inside the whole brain volume during a transcranial magnetic stimulation (TMS) procedure. The numerical solution implements the admittance method for a discretized realistic brain model derived from Magnetic Resonance Imaging (MRI). Results are in a good agreement with those obtained using commercial codes and require much less computational time. An integration of the developed codewith neuronavigation toolswill permit real-time evaluation of the stimulated brain regions during the TMSdelivery, thus improving the efficacy of clinical applications

An open-label, one-arm, dose-escalation study to evaluate safety and tolerability of extremely low frequency magnetic fields in acute ischemic stroke

Extremely low frequency magnetic fields (ELF-MF) could be an alternative neuroprotective approach for ischemic stroke because preclinical studies have demonstrated their effects on the mechanisms underlying ischemic damage. The purpose of this open-label, one arm, dose-escalation, exploratory study is to evaluate the safety and tolerability of ELF-MF in patients with acute ischemic stroke. Within 48 hours from the stroke onset, patients started ELF-MF treatment, daily for 5 consecutive days. Clinical follow-up lasted 12 months. Brain MRI was performed before and 1 month after the treatment. The distribution of ELF-MF in the ischemic lesion was estimated by dosimetry. Six patients were stimulated, three for 45 min/day and three for 120 min/day. None of them reported adverse events. Clinical conditions improved in all the patients. Lesion size was reduced in one patient stimulated for 45 minutes and in all the patients stimulated for 120 minutes. Magnetic field intensity within the ischemic lesion was above 1 mT, the minimum value able to trigger a biological effect in preclinical studies. Our pilot study demonstrates that ELF-MF are safe and tolerable in acute stroke patients. A prospective, randomized, placebo-controlled, double-blind study will clarify whether ELF-MFs could represent a potential therapeutic approach

Relazione tra stress finanziario e capacita produttiva. Un'indagine empirica con modelli var.

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Chimica farmaceutica: farmaci sistemici: Lezioni del prof. Ettore Novellino

[English]:For thousands of years, pharmacological knowledge coming from natural remedies, has been handed down from generation to generation, without any awareness of the ways in which preparations are made to face diseases. The advent of pharmaceutical chemistry and of the modern drug industry turned that lack of awareness into a scientific knowledge that changed the destiny of the human race. The twenty-eight chapters of this book, are taken from the lectures held by Professor Ettore Novellino every year in his course “Pharmaceutical Chemistry and Toxicology 2”. The first chapters address the basic notions of drugs, homeostasis, pharmacopoeia, and receptor; then, the different pharmaceutical classes are introduced by analyzing their pharmacological and chemical aspects. In particular, the structural study of the interaction between drugs and receptors or biological enzymes gives the fundamentals to connect the chemical and stereochemical properties of a compound family, with the biological activity, a correlation better known as Quantitative Structure-Activity Relationship (QSAR). Several examples of the synthesis of some of the most historically renown drugs, provided at the end of each chapter, integrate the book./ [Italiano]: Per migliaia di anni, la conoscenza farmacologica proveniente dai rimedi naturali è stata tramandata di generazione in generazione senza alcuna consapevolezza riguardo le modalità d’azione delle preparazioni allestite per affrontare le malattie. L’avvento della chimica farmaceutica e della moderna industria del farmaco ha permesso di tradurre quell’assenza di consapevolezza in un sapere scientifico capace di rivoluzionare le sorti dell’umanità. I ventotto capitoli di questo libro sono tratti dalle lezioni che il professor Ettore Novellino tiene ogni anno per il suo corso di “Chimica farmaceutica e tossicologica 2”. Il testo prende avvio dalle nozioni basilari di farmaco, omeostasi, farmacoforo e recettore e affronta le varie classi di farmaci analizzandone gli aspetti chimici e farmacologici. In particolare, lo studio strutturale dell’interazione tra il farmaco e il recettore o l’enzima biologico, fornisce al lettore le basi per correlare le proprietà chimiche e stereochimiche di una famiglia di composti all’attività biologica, correlazione meglio conosciuta come “relazione quantitativa struttura-attività” (QSAR). Completano il libro alcuni esempi, posti in chiusura di ogni capitolo, di sintesi dei farmaci storicamente più noti

Patient semi-specific computational modeling of electromagnetic stimulation applied to neuroprotective treatments in acute ischemic stroke

Neuroprotective effects of pulsed electromagnetic fields (PEMFs) have been demonstrated both in vivo and in vitro. Moreover, preliminary clinical studies have been conducted and suggested PEMFs as a possible alternative therapy to treat acute ischemic stroke. In this work, we show that it’s possible to build-up a patient semi-specific head model, where the 3D reconstruction of the ischemic lesion of the patient under treatment is inserted in the head of the human body model “Duke” (v.1.0, Zurich MedTech AG). The semi-specific model will be used in the randomized, placebo-controlled, double-blind study currently ongoing. Three patients were modelled and simulated, and results showed that each ischemic lesion experiences a magnetic flux density field comparable to the one for which biological effects have been attested. Such a kind of dosimetric analysis reveals a reliable tool to assess the correlation between levels of exposure and the beneficial effect. Thus, once the on-going double blind study is complete it will prove if PEMFs treatment triggers a clinical effect, and we will then be able to characterize a dose-response curve with the methodology arranged in this study

An open-label, one-arm, dose-escalation study to evaluate safety and tolerability of extremely low frequency magnetic fields in acute ischemic stroke

Extremely low frequency magnetic fields (ELF-MF) could be an alternative neuroprotective approach for ischemic stroke because preclinical studies have demonstrated their effects on the mechanisms underlying ischemic damage. The purpose of this open-label, one arm, dose-escalation, exploratory study is to evaluate the safety and tolerability of ELF-MF in patients with acute ischemic stroke. Within 48 hours from the stroke onset, patients started ELF-MF treatment, daily for 5 consecutive days. Clinical follow-up lasted 12 months. Brain MRI was performed before and 1 month after the treatment. The distribution of ELF-MF in the ischemic lesion was estimated by dosimetry. Six patients were stimulated, three for 45 min/day and three for 120 min/day. None of them reported adverse events. Clinical conditions improved in all the patients. Lesion size was reduced in one patient stimulated for 45 minutes and in all the patients stimulated for 120 minutes. Magnetic field intensity within the ischemic lesion was above 1 mT, the minimum value able to trigger a biological effect in preclinical studies. Our pilot study demonstrates that ELF-MF are safe and tolerable in acute stroke patients. A prospective, randomized, placebo-controlled, double-blind study will clarify whether ELF-MFs could represent a potential therapeutic approach

Gastrinomas and non-functioning pancreatic endocrine tumors in multiple endocrine neoplasia syndrome type-1 (MEN-1)

Purpose: Illustrate imaging findings of gastrinomas and non-functioning pancreatic endocrine tumors (NF-PNET) in a patient with multiple endocrine neoplasia type-1 (MEN-1) syndrome with a radiologic-pathologic correlation for both along with the results of a 13 yrs observational study. Methods: A 48 yrs old male patient with MEN-1 and a Zollinger-Ellison syndrome was submitted to a duodeno-cephalopancreatectomy (DCP) extended to the pancreatic body to remove several gastrinomas shown by an endoscopic-ultrasonography as well as a large (> 2 cm) hypo-vascular pancreatic nodule shown by a contrast-enhanced multi-detector CT (CE-MDCT). Further conventional (CT/MR) and functional imaging (68Ga-PET-DOTA-TOC) studies were performed over the next 13 years. Results: Up to 14 gastrin-positive NET-G1 (pT2,N1) as well as a single PNET-G2 (pT2,N0) were found at histo-pathology which also showed a NET-G1 in the uncinate process where CE-MDCT documented a 9 mm hyper-vascular nodule. A 7 mm pancreatic nodule with identical contrast-enhancement pattern was also shown at the level of the pancreatic tail which was left to preserve endocrine function. At this level, follow-up studies documented the occurence of a small (< 1 cm) hypo-vascular nodule which was metastatic at presentation and rapidly progressed under somastatin-analogs therapy whereas the hyper-vascular nodule remained stable over 13 years. Both the pancreatic lesion as well as the hepatic metastasis showed pathologic uptake of the radiotracer with a SUVmax of 6.3 and 29.5, respectively, allowing the patient to be scheduled for a Peptide Receptor Radionuclide Therapy performed with 29.6 GBq of 177Lu-Oxotreotide. Conclusions: Contrast-enhancement patterns are correlated with both the histological grade as well as the biological behaviour of PNETS