Effect of acute and repeated administration of paracetamol on opioidergic and serotonergic systems in rats.

Objective and design: We investigated the antinociceptiveeffect of paracetamol or morphine after repeatedadministration and the changes in the characteristics of centralμ-, κ- and 5-HT2 receptors.Treatment: Male rats were injected twice a day for sevendays with paracetamol (400 mg/kg, i. p.) or morphine (5 mg/kg, s. c.).Methods: The antinociceptive effect was evaluated 30 minafter single and multiple doses of paracetamol and morphinethrough the hot-plate test. Binding techniques were used toevaluate the receptor characteristics in the frontal cortex.Results: Both paracetamol and morphine induced an antinociceptiveeffect on day 1 but only paracetamol maintainedthis effect for seven days while morphine did not.The number of μ-opioid receptors decreased on days 1, 3,and 7 by a similar percentage after paracetamol administration(by 29, 31 and 34 %, respectively), while morphineproduced a progressive decrease in comparison with controls(by 37, 49 and 60 %, respectively) and κ-opioid receptorswere unaffected. Both drugs similarly decreased the 5-HT2receptor number on all days of treatment (by about 30 %).Conclusions: The opioidergic and serotonergic systems areinvolved in different ways in the induction and maintenanceof antinociception after paracetamol or morphine treatment

Anxiolytic-like effects of nociceptin/orphanin FQ in the elevated plus maze and in the conditioned defensive burying test in rats

Different reports suggest that nociceptin/orphanin FQ (N/OFQ) may have either anxiolytic- or anxiogenic-like effect in rodents. Since N/OFQ elicits hypolocomotion, which undergoes rapid tolerance, and hypolocomotion may be associated to emotional consequences, the present study was designed to investigate the effect of N/OFQ on anxiety after development of tolerance to its hypolocomotor effect. The effect of single or double intracerebroventricular (i.c.v.) injection of N/OFQ was evaluated on anxiety-related behaviors in rats, in the elevated plus maze (EPM) and conditioned defensive burying (CDB) tests. After single administration, N/OFQ displayed an anxiogenic-like pattern of response on the elevated plus maze but hypolocomotion was also observed. Conversely, in the CDB test, N/OFQ induced a clear-cut anxiolytic pattern. To produce tolerance to N/OFQ-induced hypolocomotion the peptide was administered by two i.c.v. injections separated by 120 min; in these conditions it decreased the expression of anxiety-related behaviors in both tests without affecting locomotor activity. The nociceptin/orphanin FQ peptide (NOP) receptor antagonist UFP-101 significantly reduced the effects of N/OFQ to control values in either tests. Corticosterone levels were significantly increased after a single N/OFQ administration (not in a dose-dependent manner) but this increase did not reach significance after double administration (1 nmol/rat). Our results support the idea that N/OFQ may act as an anxiolytic-like agent in the rat; the apparent anxiogenic-like effect observed following its single administration in the EPM may be consequent to its, effect on locomotion. (c) 2006 Elsevier Inc. All rights reserved

Mercury Dispersion through Streams Draining The Mt. Amiata District, Southern Tuscany, Italy

Abstract The Mt. Amiata area hosts the 3 rd largest Hg district in the world, overlapping with a present-day geothermal system that is exploited for energy production. Mining activity ceased in 1980; remediation of mining areas was only partial, and is still under way. A significant transport of mercury is documented in the streams draining the district. By far the largest output occurs to the southeast in the Paglia River catchment; this river is tributary of Tiber River, the largest river of central Italy. A much smaller transport occurs to the north, in the Orcia-Ombrone catchment. Most transport is in particulate form; mercury is temporarily stored in stream and overbank sediments, and can be significantly mobilized and redistributed by extreme events such as flash floods. Transfer to the biosphere and food chain is not negligible, as some fish in Paglia and Tiber Rivers show Hg contents that may be harmful for human consumption. The overall output from the Monte Amiata district represents a significant contribution to the Mediterranean Sea budget of this metal

Butyrylcholinesterase and Acetylcholinesterase polymorphisms in Multiple Sclerosis patients: Implication in peripheral inflammation

Multiple Sclerosis (MS) is an autoimmune disease, having not fully understood aetiology, and both genetic and environmental factors contribute to the pathogenesis of the disease. The cholinergic system has been indicated as a mediator of neuro-immune interactions, as well as an internal regulator of immune responses. The aim of the present research was to assess the associations between BChE and AChE genetic variations and serum cholinergic and inflammatory profiles in 102 Relapsing Remitting-MS patients and 117 healthy controls. An increased frequency of the BChE K-allele in MS patients as compared to controls was found. In addition, data showed that patients had higher BChE enzymatic activity, which is increased by the presence of the polymorphic allele and reduced amounts of circulating ACh. AChE polymorphism was significantly associated to reduced activity in both patients and controls. We propose that serum BChE and AChE activity may be used as a secondary markers to assess the role of non-neuronal cholinergic system in regulating peripheral inflammation via ACh regulation. This pilot study shed light on the role of the non-neuronal cholinergic system in immune cells to better understand MS pathogenesis. The cross-talk between the periphery and the CNS could have a new undescribed crucial role for MS, regarded as a systemic disease

Brain correlates of spike and wave discharges in GLUT1 deficiency syndrome

Purpose To provide imaging biomarkers of generalized spike-and-wave discharges (GSWD) in patients with GLUT1 deficiency syndrome (GLUT1DS). Methods Eighteen GLUT1DS patients with pathogenetic mutation in SLC2A1 gene were studied by means of Video-EEG simultaneously recorded with functional MRI (VideoEEG-fMRI). A control group of sex and age-matched patients affected by Genetic Generalized Epilepsy (GGE) with GSWD were investigated with the same protocol. Within and between groups comparison was performed as appropriated. For GLUT1DS, correlations analyses between the contrast of interest and the main clinical measurements were provided. Results EEG during fMRI revealed interictal GSWD in 10 GLUT1DS patients. Group-level analysis showed BOLD signal increases at the premotor cortex and putamen. With respect to GGE, GLUT1DS patients demonstrated increased neuronal activity in the putamen, precuneus, cingulate cortex, SMA and paracentral lobule. Whole-brain correlation analyses disclosed a linear relationship between the GSWD-related BOLD changes and the levels of glycorrhachia at diagnosis over the sensory-motor cortex and superior parietal lobuli. Conclusion The BOLD dynamics related to GSWD in GLUT1DS are substantially different from typical GGE showing the former an increased activity in the premotor-striatal network and a decrease in the thalamus. The revealed hemodynamic maps might represent imaging biomarkers of GLUT1DS, being potentially useful for a precocious diagnosis of this genetic disorder

Respiratory mechanics and diaphragmatic dysfunction in COPD patients who failed non-invasive mechanical ventilation

Background. Although non-invasive mechanical ventilation (NIV) is the gold standard treatment for patients with acute exacerbation of COPD (AECOPD) developing respiratory acidosis, failure rates still range from 5% to 40%. Recent studies have shown that the onset of severe diaphragmatic dysfunction (DD) during AECOPD increases risk of NIV failure and mortality in this subset of patients. Although the imbalance between the load and the contractile capacity of inspiratory muscles seems the main cause of AECOPD-induced hypercapnic respiratory failure, data regarding the influence of mechanical derangement on DD in this acute phase are lacking. With this study we investigate the impact of respiratory mechanics on diaphragm function in AECOPD patients experiencing NIV failure. Methods. Twelve AECOPD with respiratory acidosis admitted to the Respiratory ICU of the University Hospital of Modena from 2017-2018 undergoing mechanical ventilation (MV) due to NIV failure were enrolled. Static respiratory mechanics and end expiratory lung volume (EELV) were measured after 30 minutes of volume control mode MV. Subsequently transdiaphragmatic pressure (Pdi) was calculated by means of a sniff maneuver (Pdisniff) after 30 minutes of spontaneous breathing trial. Linear regression analysis and Pearson’s correlation coefficient served to assess associations. Results. Average Pdisniff was 23.3 (standard deviation, SD=29) cmH20 with 3 patients presenting bilateral diaphragm palsy. Pdisniff was directly correlated with static lung elastance (r=0.69, p=0.001) while inverse correlation was found with dynamic intrinsic PEEP (r=-0.73, p=0.007). No significant correlation was found with static intrinsic PEEP (r=-0.55, p=0.06), EELV (r=-0.4, p=0.3), airway resistance (r=-0.2, p=0.54), chest wall and total elastance (r=-0-01, p=0.96 and r=0.3, p=0.36 respectively). Significant linear inverse correlation was found between Pdi/Pdisniff and Pdisniff (r=-0.82, p=0.02). Conclusion. The causes of extreme DD in AECOPD patients who experienced NIV failure might be predominantly mechanical, driven by a severe dynamic hyperinflation that overlaps on an elastic lung substrate favoring volume overload

Norovirus infection results in eIF2α independent host translation shut-off and remodels the G3BP1 interactome evading stress granule formation.

Viral infections impose major stress on the host cell. In response, stress pathways can rapidly deploy defence mechanisms by shutting off the protein synthesis machinery and triggering the accumulation of mRNAs into stress granules to limit the use of energy and nutrients. Because this threatens viral gene expression, viruses need to evade these pathways to propagate. Human norovirus is responsible for gastroenteritis outbreaks worldwide. Here we examined how norovirus interacts with the eIF2α signaling axis controlling translation and stress granules. While norovirus infection represses host cell translation, our mechanistic analyses revealed that eIF2α signaling mediated by the stress kinase GCN2 is uncoupled from translational stalling. Moreover, infection results in a redistribution of the RNA-binding protein G3BP1 to replication complexes and remodelling of its interacting partners, allowing the avoidance from canonical stress granules. These results define novel strategies by which norovirus undergo efficient replication whilst avoiding the host stress response and manipulating the G3BP1 interactome

Expression of HOXB7 in the lung of patients with idiopathic pulmonary fibrosis: a proof of concept study.

Background: The molecular pathways involved in the onset and progression of idiopathic 60 pulmonary fibrosis (IPF) still need to be fully clarified, being some shared with lung cancer development. HOXB7, a member of homeobox (HOX) gene family, has been found involved in various cancers. Methods: Immunohistochemical (IHC) analysis was run on lung tissue samples from surgical lung biopsy (SLB) of 19 patients with IPF retrospectively selected from the IPF database of the 64 University Hospital of Modena. HOXB7 expression was quantified analyzed and compared it with that of 5 patients with no evidence of pulmonary fibrosis as controls. Results: IHC quantificationthe semi-quantitative analysis of IHC showed that HOXB7 signal intensityprotein expression was higher in IPF patients as compared to controls (difference between means = 15.906.2±6.02.37, p=0.0157). Further, HOXB7 expression resulted higher in IPF patients with a higher extent of fibrosis (50-75%) at high resolution computer tomography compared to those with lower extent (0-25%) (difference between means = 25.74 ± 6.72, p=0.004). Conclusions: The expression of HOXB7 is higher in the lung of IPF patients as compared to controls, being represented in different cellular compartments within the lung niche. Further investigations are needed to clarify its role in the pathogenesis and progression of IPF

A pilot study on the application of the current European guidelines for the management of acute coronary syndrome without elevation of ST segment (NSTEMI) in the Emergency Department setting in the Italian region Lazio.

Background: In 2011 the European Society of Cardiology published the new guidelines for the treatment and management of acute coronary syndrome without elevation of the ST segment (NSTEMI). For the treatment of the syndrome, the use of P2Y12 inhibitors in addition to aspirin was strongly recommended (evidence IA). We studied the application of this recommendation in the setting of the emergency department in the vast and uneven area of the Italian region Lazio, three years after the release of these drugs in Italy. Methods: 121 consecutive patients (65% older than 65 years) affected by NSTEMI were recruited between May and July 2013. During the transition in the emergency department data was collected on patient's symptoms, syndrome severity and type & timing of treatments chosen. Adherence to the guidelines was evaluated considering the number of "good treated" patients: these being the patients that received at least 80% of the main five recommendations on percutaneous coronary intervention (PCI) timing, antiplatelet and anti-coagulant therapy suggested by the European Cardiology Task Force (ESC guidelines, 2011) for the very acute phase of NSTEMI. Results: Patients were treated with: 1) 35% of cases with double antiplatelet therapy and anticoagulation (DAPT+AC), 2) 22% of cases with single antiplatelet and anticoagulation (SAPT+AC), 3) 6% of cases with a single antiplatelet therapy (SAPT), 4) 6% of cases with a double antiplatelet therapy (DAPT) and 5) 24% of cases did not receive any therapy. Data on PCI was available for 95 patients and, of these, only 82% of the patients underwent the procedure. The percentage of "good treated" patients were among of 20-40%, depending on PCI timing – as guidelines suggested – was considered as mandatory (20,5%) or as the extreme time limit (40%). Significant differences were found between patients treated in a central hospital with a hemodynamic laboratory active 24/24hr (HUB) and patients treated in the other hospital (SPOKE). HUBs showed a higher percent of "good treated" patients, a higher percentage of early invasive treated and a better adherence to recommended pharmacological therapy. Conclusions: A significant number of patients did not receive adequate treatment during the emergency department stay. The absence of hemodynamic services increases the risk of inadequate treatment

New insights to assess the consolidation of stone materials used in built heritage: the case study of ancient graffiti (Tituli Picti) in the archaeological site of Pompeii

Abstract Tituli Picti are an ancient form of urban graffiti very common in the archaeological site of Pompeii (Naples, South—Italy). They are generally made of red pigments applied on walls of Campanian ignimbrite. This paper deals with a scientific investigation aimed to their conservation. This is a challenging task since it requires a multidisciplinary approach that includes restorers, archaeologists and conservation scientists. The study has provided suggestions on the proper way to conserve Tituli Picti over time. In the present work, several specimens of Campanian ignimbrite were painted with red earth pigment; lime and Arabic gum have been used as binders as well. Such painted stones were treated with three consolidants: a suspension of reactive nanoparticles of silica, ethyl silicate and an acrylic microemulsion. Treated and untreated specimens were subjected to thermal aging, artificial solar radiation and induced crystallization decay. It has been assessed the colorimetric variations induced by treatments. Moreover, the micromorphologic features of the consolidated surfaces have been highlighted by means of electron microscope observations. The scotch tape test allowed to compare the superficial cohesion induced by the three used products. According to the results, ethyl silicate seems to represent the most successful product