The role of adenosine and P2Y receptors expressed by multiple cell types in pain transmission

The role of extracellular nucleotides and nucleosides as signaling molecules in cell-to-cell communication has now been clearly established. This is particularly true in the central and peripheral nervous system, where purines and pyrimidines are involved in both physiological and pathological interactions between neurons and surrounding glial cells. It can be thus foreseen that the purinergic system could represent a new potential target for the development of effective analgesics, also through the normalization of neuronal functions and the inhibition of glial cell activation. Research in the last 15 years has progressively confirmed this hypothesis, but no purinergic-based analgesics have reach the market so far; in the present review we have collected the more recent discoveries on the role of G protein-coupled P2Y nucleotide and of adenosine receptors expressed by both neurons and glial cells under painful conditions, and we have highlighted some of the challenges that must be faced to translate basic and preclinical studies to clinics

P2Y purinergic receptors: new targets for analgesic and antimigraine drugs

Millions of individuals worldwide suffer from acute and, more severely, chronic pain conditions (e.g., neuropathic pain, and migraine). The latter bear tremendous personal, familial, and social costs, since sufferers and their relatives undergo a complete turnaround of their lives with the search of relief from pain becoming their pivotal thought. Sadly, to date no effective pharmacological approaches are available which can alleviate chronic pain significantly or in the long run in all patients. The current central strategy for the development of new and effective painkillers lies in the hypothesis that cellular and/or molecular players in nociception must exists that are not targeted by "classical" analgesics, and therefore researchers have put tremendous efforts into the in-depth analysis of the pathways leading to pain development and maintenance over time. In this complex scenario, two outsiders are now taking the center stage: glial cells in sensory ganglia and in the central nervous system, thanks to their ability to communicate with neurons and to modulate their firing, and the purinergic system. Extracellular purine and pyrimidine nucleotides are involved in the physiology of virtually every body district, and their extracellular concentrations massively increase under pathological situations, suggesting that they might represent potential targets for the modulation of disease-associated symptoms, like pain. Here, we provide an overview of the present knowledge of the role of nucleotides in nociception, with a particular emphasis on G protein-coupled P2Y receptors and their involvement in the communication between first- and second-order neurons in sensory nerve pathways and surrounding glial cells

Dynamic hysteresis in Finemet thin films

We performed a series of dynamic hysteresis measurements on three series of Finemet films with composition Fe$_{73.5}$Cu$_1$Nb$_3$Si$_13.5$B$_9$, using both the longitudinal magneto-optical Kerr effect (MOKE) and the inductive fluxometric method. The MOKE dynamic hysteresis loops show a more marked variability with the frequency than the inductive ones, while both measurements show a similar dependence on the square root of frequency. We analyze these results in the frame of a simple domain wall depinning model, which accounts for the general behavior of the data.Comment: 3 pages, 3 figure

A nonparametric approach for model individualization in an artificial pancreas

The identification of patient-tailored linear time invariant glucose-insulin models is investigated for type 1 diabetic patients, that are characterized by a substantial inter-subject variability. The individualized linear models are identified by considering a novel kernel-based nonparametric approach and are compared with a linear time invariant average model in terms of prediction performance by means of the coefficient of determination, fit, positive and negative max errors, and root mean squared error. Model identification and validation are based on in-silico data collected from the adult virtual population of the UVA/Padova simulator. The data generation involves a protocol designed to produce a sufficient input excitation without compromising patient safety, compatible also with real life scenarios. The identified models are exploited to synthesize an individualized Model Predictive Controller (MPC) for each patient, which is used in an Artificial Pancreas to maintain the blood glucose concentration within an euglycemic range. The MPC used in several clinical studies, synthesized on the basis of a non-individualized average linear time invariant model, is also considered as reference. The closed-loop control performance is evaluated in an in-silico study on the adult virtual population of the UVA/Padova simulator in a perturbed scenario, in which the MPC is blind to random variations of insulin sensitivity in each virtual patient. © 2015, IFAC (International Federation of Automatic Control) Hosting by Elsevier Ltd. All rights reserved

Is demagnetization an efficient optimization method?

Demagnetization, commonly employed to study ferromagnets, has been proposed as the basis for an optimization tool, a method to find the ground state of a disordered system. Here we present a detailed comparison between the ground state and the demagnetized state in the random field Ising model, combing exact results in $d=1$ and numerical solutions in $d=3$. We show that there are important differences between the two states that persist in the thermodynamic limit and thus conclude that AC demagnetization is not an efficient optimization method.Comment: 2 pages, 1 figur

Intracranial pressure monitoring during percutaneous tracheostomy "Percutwist" in critically ill neurosyrgery patients

BACKGROUND: Tracheostomy is commonly required as part of the management of patients with severe brain damage. Percutaneous dilation tracheostomy is increasingly used in intensive care unit as an alternative to standard surgical tracheostomy. However, this procedure carries the risk of neurological complications, particularly in patients with intracranial hypertension. In this study, we sought to quantify the effects of Percutwist(R) tracheostomy (Rusch-Teleflex Medical) on intracranial pressure (ICP), cerebral perfusion pressure (CPP), arterial CO(2) tension (Paco(2)), and arterial O(2) tension (Pao(2)), in 65 consecutive critically ill patients admitted to the neurosurgical intensive care unit, undergoing bedside percutaneous tracheostomy. METHODS: Sixty-five patients (29 men, 36 women, mean age 43 yr, 7 +/- 10.6) Glasgow Coma Scale or=8, requiring long-term ventilatory support with a stable ICP or=20 mm Hg were included. Elective percutaneous tracheostomies were performed at the bedside under endoscopic fiberoptic control. Intraoperative monitoring included continuous: electrocardiogram, Spo(2), invasive arterial blood pressure, ICP, CPP = mean arterial blood pressure-ICP). Episodes of ICP increment above 20 mm Hg or CPP decrease below 60 mm Hg (lasting more than 3 min) were recorded; hypoxia was defined as Pao(2) below 90 mm Hg, hypercarbia as Paco(2) more than 40 mm Hg. RESULTS: Eighteen episodes of intracranial hypertension were recorded in 11 patients. No statistically significant modification of monitored variables was recorded, although the transient ICP increase was very close to statistical significance (P = 0.051). No episodes of CPP reduction below 60 mm Hg occurred. Six percent of patients developed hypercarbia. CONCLUSIONS: Percutwist tracheostomy is a single-step method which allows for effective ventilation during the procedure, thus reducing the risk of hypercarbia and development of intracranial hypertension. The technique did not cause secondary pathophysiological insult and could be considered safe in a selected population of brain-injured patients

Nonfatal cerebral air embolism after dental surgery.

After removal of four impacted third molars under general anesthesia, our patient developed subcutaneous emphysema, pneumothorax, pneumopericardium, and pneumomediastinum. Soon thereafter, coma with generalized epileptic status ensued. A cerebral magnetic resonance and single photon emission computed tomography showed hypoperfusion of the right thalamus and parietal, temporal, and frontal cortices. The likely mechanism was injection of air by the high-speed dental drill through the soft tissue adjacent to the roots of the lower molars. We were unable to find any previous report of systemic air embolism after oral surgery

Investigation of scaling properties of hysteresis in Finemet thin films

We study the behavior of hysteresis loops in Finemet Fe$_{73.5}$Cu$_1$Nb$_3$Si$_{18.5}$B$_4$ thin films by using a fluxometric setup based on a couple of well compensated pickup coils. The presence of scaling laws of the hysteresis area is investigated as a function of the amplitude and frequency of the applied field, considering sample thickness from about 20 nm to 5 $\mu$m. We do not observe any scaling predicted by theoretical models, while dynamic loops show a logarithmic dependence on the frequency.Comment: 2 pages, 2 figure