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The nociceptin (NOP) receptor is a G-protein-coupled receptor whose natural ligand is the NOP/orphanin FQ (N/OFQ) peptide. Evidence from pharmacological studies suggests that the N/OFQ system is implicated in the regulation of several addiction-related phenomena, such as drug intake, withdrawal, and relapse. Here, to further explore the role of NOP system in addiction, we used NOP (−/−) rats to study the motivation for cocaine, heroin, and alcohol self-administration in the absence of N/OFQ function. Conditioned place preference (CPP) and saccharin (0.2% w/v) self-administration were also investigated. Results showed that NOP (−/−) rats self-administer less cocaine (0.25, 0.125, or 0.5 mg/infusion) both under a fixed ratio 1 and a progressive ratio schedule of reinforcement compared with wild-type (Wt) controls. Consistently, cocaine (10 mg/kg, i.p.) was able to induce CPP in Wt but not in NOP (−/−). When NOP (−/−) rats were tested for heroin (20 μg/infusion) and ethanol (10% v/v) self-administration, they showed significantly lower drug intake compared with Wt. Conversely, saccharin self-administration was not affected by NOP deletion, excluding the possibility of nonspecific learning deficits or generalized disruption of reward mechanisms in NOP (−/−) rats. These findings were confirmed with pharmacological experiments using two selective NOP antagonists, SB-612111 and LY2817412. Both drugs attenuated alcohol self-administration in Wt rats but not in NOP (−/−) rats. In conclusion, our results demonstrate that genetic deletion of NOP receptors confers resilience to drug abuse and support a role for NOP receptor antagonism as a potential treatment option for drug addiction.

A 49-year-old man without cardiovascular risk factors, recently diagnosed of asthma and rino-sinusal polyposis, entered the Emergency Department for chest pain, shortness of breath and non-productive cough. The patient was in stable conditions. Laboratory exams showed eosinophilic leucocytosis (WBC 33.000/sqmm, 60% eosinophils) and a mild elevation of C-reactive protein (CRP 2,2 mg/dL). ECG showed a sinus rhythm with flat T-waves in the antero-lateral leads. Troponin values were high but not suggestive of acute myocardial damage (9900 - 9700 ng/L). Echocardiography showed normal biventricular volumes with moderately depressed left ventricular ejection fraction (40%), hypokinesia of the antero-lateral wall in the mid-apical segments and mild pericardial effusion.During the hospital stay he developed progressive respiratory failure, and he was transferred to a tertiary center to perform an endomyocardial biopsy (EMB) in the suspicion of acute myocarditis. EMB showed multifocal interstitial and sub-endocardial inflammatory infiltrates (predominantly eosinophils) with foci of myocellular damage, small vessels wall inflammation with hypertrophy of the muscular tunica. The overall picture was consistent with diffuse moderate eosinophilic myocarditis with small vessels vasculitis. The right heart cath performed in the same procedure and during diuretic therapy showed a normal hemodynamic profile (RAP 5 mmHg, PCWP 13 mmHg, CI 3,7 L/min/sqm). The patient was treated with high dose steroids, first intravenously (methylprednisolone 125 mg/day for three days), then orally (prednisone 80 mg/day) in slow decalage until a maintenance dose of 12.5 mg daily.The recent-onset of asthma with hyper-eosinophilia and rhino-sinus-bronchial syndrome in the light of the present cardiac condition was consistent with eosinophilic granulomatosis with polyangiitis (EGPA). Chest CT showed two areas of ground glass at the left superior and right superior lobes. Other potential haematological and infective causes of hyper eosinophilia and viral causes of myocarditis were ruled out.After the treatment, his clinical conditions improved, ECG was completely normalized, left ventricular systolic function improved (LVEF 50%) and eosinophil count was significantly reduced (Eosinophils 830/sqmm, 8,9%), whereas CT showed resolution of the lung infiltrates.One month after discharge, the patient was still asymptomatic. Cardiac MRI showed normal biventricular ejection fraction (LVEF 55%) with circumferential subendocardial fibrosis involving only the left ventricle. EMB showed a complete resolution of the inflammatory infiltrates and of the vasculitic aspects. Eosinophil count was elevated (5660/sqmm, 36%). Therefore, steroidal dose was raised to 50 mg/day. After rheumatologic evaluation, a steroidal sparing strategy with cyclophosphamide and anti-IL5 antibody Mepolizumab was adopted, with good laboratory response. Three months later, cardiac MRI showed no signs of active disease. No further EMB was scheduled.Through the presentation of this unusual cause of acute myocarditis, we want to underscore the importance of an early referral to a tertiary level center of patients with suspected myocarditis and reduced systolic function and the usefulness of histology to guide medical therapy in specific forms of myocarditis that can lead to a potential complete recovery.

The Monti Sibillini National Park is a recently borne protected area in the central Apennines that has become an important tourist destination. Mountain grasslands and woods have made it also a suitable habitat for sheep and bovine cattle, as well as for wild animals such as the wild bore and the roe deer. Therefore, a preliminary investigation was conducted to assess the risk of transmission of tick-borne zoonoses, such as Lyme disease and Babesiosis, by actively looking for both the arthropod vector and the causative agent. For two consecutive years, ambushing ticks were collected in four distinct geographical areas, comprehensive of many highly frequented tourist places. The tick fauna, tick habitats and the seasonal distribution of the different tick life stages collected with the method of "flagging and dragging" have been reported. Almost all the collected specimens belonged to the species Haemaphysalis punctata (Canestrini and Fanzago) (Acari: Ixodidae), which was found moderately infected with Babesia spp. Only a few Ixodes ricinus (Linnaeus) ticks, the most competent vector of Lyme disease, were found and on PCR examination all of them resulted negative as far as the infectious agent Borrelia burgdorferi sensu lato (Johnson) is concerned