Adenosine A2A receptor antagonist treatment of Parkinson’s disease

Adenosine A2A receptors have a unique cellular and regional distribution in the basal ganglia (BG), being particularly concentrated in areas richly innervated by dopamine (DA) such as the caudateputamen, otherwise called striatum, and the globus pallidus. Adenosine A2A and DA D2 receptors are capable of forming functional heteromeric complexes and are colocalised in striatopallidal neurons. Based on the peculiar cellular and regional distribution of this receptor and in line with data showing that A2A receptor antagonists improve motor symptoms of Parkinson’s disease (PD) in animal models and in clinical trials, A2A receptor antagonists have emerged as an attractive nondopaminergic target to improve the motor deficits that characterise PD. Experimental data have also shown that A2A receptor antagonists are capable of exerting a neuroprotective effect and do not induce neuroplasticity phenomena that complicate long-term dopaminergic treatments. The present review will provide an updated summary of results reported in the literature concerning the biochemical characteristics and BG distribution of A2A receptors. We subsequently aim to examine the effects of adenosine A2A antagonists in rodent and primate models of PD and L-DOPA-induced dyskinesia. Finally, conclusive remarks will be made on the neuroprotective effects of A2A antagonists and on the translation of adenosine A2A receptor antagonists in the treatment of PD.peer-reviewe

Adenosine A2A receptor antagonist treatment of Parkinson’s disease

Adenosine A2A receptors have a unique cellular and regional distribution in the basal ganglia (BG), being particularly concentrated in areas richly innervated by dopamine (DA) such as the caudateputamen, otherwise called striatum, and the globus pallidus. Adenosine A2A and DA D2 receptors are capable of forming functional heteromeric complexes and are colocalised in striatopallidal neurons. Based on the peculiar cellular and regional distribution of this receptor and in line with data showing that A2A receptor antagonists improve motor symptoms of Parkinson’s disease (PD) in animal models and in clinical trials, A2A receptor antagonists have emerged as an attractive nondopaminergic target to improve the motor deficits that characterise PD. Experimental data have also shown that A2A receptor antagonists are capable of exerting a neuroprotective effect and do not induce neuroplasticity phenomena that complicate long-term dopaminergic treatments. The present review will provide an updated summary of results reported in the literature concerning the biochemical characteristics and BG distribution of A2A receptors. We subsequently aim to examine the effects of adenosine A2A antagonists in rodent and primate models of PD and L-DOPA-induced dyskinesia. Finally, conclusive remarks will be made on the neuroprotective effects of A2A antagonists and on the translation of adenosine A2A receptor antagonists in the treatment of PD.peer-reviewe

Incidence of Tetracycline and Erythromycin Resistance in Meat-Associated Bacteria: Impact of Different Livestock Management Strategies

The extensive use of antibiotics as growth promoters, or their continued abusive misuse to cure or prevent the onset of bacterial infections as occurs in the intensive farming, may have played a pivotal role in the spread of reservoirs of antibiotic resistance (AR) among food-associated bacteria including pathogens representing risks to human health. The present study compares the incidence of tetracycline and erythromycin resistances in lactic acid bacteria (LAB) and coagulase negative staphylococci (CNS) from fermented products manufacturing using meat from intensive animal husbandry (industrialized manufacturing Italian salami) and from extensive farms (artisanal sausages facilities pork and llama Argentinean sausages). A higher incidence of tetracycline resistance (TET-R) compared to erythromycin resistance (ERY-R) was observed among the 205 isolates. Unlike CNS strains, the LAB showed a significant correlation between the TET-R and the ERY-R phenotypes. Genotypic assessment shows a high correlation with tetK and tetM for the TET-R strains and with ermB and ermC for the ERY-R strains. Multiple correspondence analyses have highlighted the association between AR phenotypes and CNS species isolated from Italian salami, while the susceptible phenotypes were associated with the LAB species from Argentinean sausages. Since antibiotic resistance in meat-associated bacteria is a very complex phenomenon, the assessment of bacterial resistance in different environmental contexts with diverse farming practices and food production technologies will help in monitoring the factors influencing AR emergence and spread in animal production.EEA FamailláFil: Fontana, Cecilia Alejandra. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Famaillá; ArgentinaFil: Fontana, Cecilia Alejandra. Universita Cattolica del Sacro Cuore. Centro Ricerche Biotecnologiche; ItaliaFil: Patrone, Vania. Università Cattolica del Sacro Cuore. DISTAS; ItaliaFil: López, Constanza María. Universita Cattolica del Sacro Cuore. Centro Ricerche Biotecnologiche; ItaliaFil: Morelli, Lorenzo. Universita Cattolica del Sacro Cuore. Centro Ricerche Biotecnologiche; ItaliaFil: Morelli, Lorenzo. Università Cattolica del Sacro Cuore. DISTAS; ItaliaFil: Rebecchi, Annalisa. Universita Cattolica del Sacro Cuore. Centro Ricerche Biotecnologiche; ItaliaFil: Rebecchi, Annalisa. Università Cattolica del Sacro Cuore. DISTAS; Itali

Sassi di Matera. Per una nuova stagione

La pubblicazione raccoglie i contributi dei relatori intervenuti nel confronto pubblico di approfondimento dal titolo “Sassi: per un nuovo dialogo in città”, tenutosi a Matera il 14 e 15 dicembre 2018 e organizzato dalla Cattedra UNESCO dell’Università della Basilicata (UniBas) (nel programma ERT-Educazione Ricerca Territorio) e dalla Fondazione Sassi in occasione del venticinquesimo anniversario dell’iscrizione dei Sassi nella Lista UNESCO del Patrimonio Mondiale. In Appendice si trova una Nota di sintesi delle giornate di studio, confronto e partecipazione, che si sono tenute a Matera, in forma di tre eventi, in occasione del venticinquesimo anniversario dell’iscrizione dei Sassi alla lista del patrimonio UNESCO, e come edizione pilota del programma “ERT-Educazione Ricerca Territorio” della Cattedra UNESCO. In tale ambito si inserisce la conversazione pubblica “Sassi: per un nuovo dialogo in citta”, di cui il libro raccoglie i contributi dei relatori intervenuti. Oltre alla Nota di sintesi, è riportato per esteso anche il Report, redatto da Paolo Ceccarelli, di uno dei tre eventi, quello titolato “Patrimonio e sviluppo sostenibile: per una conoscenza circolare”, per i richiami contenuti al progetto dell’Osservatorio Sassi e per il sostegno dichiarato al progetto da parte della rete di Cattedre UNESCO TEST, in virtù dell’interesse metodologico ravvisato in tale prospettiva di lavoro scientifico e di pratica partecipativa

The endophytic microbiome of X. fastidiosa susceptible and resistant olives

A multi-factorial strategy is required to co-exist with X. fastidiosa infections, which are devastating olive trees in the southern area of Apulia (Italy). Observations in the outbreak area can provide information on potential approaches for containment. Olive cvs Leccino and FS17 show lessened symptoms and host lower bacterial populations (1,2) than cvs Ogliarola salentina, Cellina di Nardò and Kalamata. We are evaluating whether microbial communities inhabiting the xylem vessels of olive cvs showing different susceptibilities to X. fastidiosa -infection play a role in resistance. To explore these endophytic microbiomes, a whole-metagenome shotgun analysis is currently ongoing. X. fastidiosa -infected and healthy olive plants of the cultivars FS17, Leccino and Kalamata, were selected from the same plot to limit the influence of diverse soil composition and crop management. Shotgun sequencing of DNA extracted from the xylem tissues will be used to investigate the microbiome community by bio-informatic analysis. Moreover, efforts to isolate culturable microorganisms to be used in antagonistic assays against X. fastidiosa, will be performed. Concurrently, the X. fastidiosa-biocontrol potency of Paraburkholderia phytofirmans PsJN strain, whose beneficial effects in the reduction of symptoms in Pierce’s Disease (3) have been recently described, are under evaluation. We are testing the ability of P. phytofirmans to colonise xylem vessels and interact with X. fastidiosa in tobacco and olive

Failure to recognize preoperatively high-risk endometrial carcinoma is associated with a poor outcome

n/

Association between elevated TGA-IgA titers and older age at diagnosis with absence of HBV seroconversion in celiac children

Patients with celiac disease can have a low rate of protective hepatitis B (HBV) antibody titers after vaccination. We aimed to evaluate the HBV seroconversion in celiac disease (CD) children at the time of diagnosis as well as to identify the presence of possible predictive factors. Celiac disease children were prospectively enrolled and tested for antibodies against the S protein of HBV (HBsAg) at time of diagnosis between January 2009 and February 2020. Based on the serologic response to the vaccine, “responders” and “non-responders” were identified. Statistical analysis has been performed through R statistical software (3.5.1 version, R core Team) Of 96 CD children evaluated, 41.7% (n = 40) showed non-protective or absent antibody titers against HBV. Elevated IgA-antibodies against transglutaminase 2 (TGA-IgA) values and older age at diagnosis were associated with an absent seroconversion to HBV vaccine, while presenting symptoms were not significant. An elevated prevalence of absent seroconversion to HBV vaccine exists in this cohort of CD patients at the time of disease diagnosis. Elevated TGA-IgA titers and older age at diagnosis seem to negatively predict seroconversion. Further studies are needed to identify the real profile of “non-responders”, aiming to organize surveillance and eventual revaccination strategy

Variations in Biodistribution and Acute Response of Differently Shaped Titania Nanoparticles in Healthy Rodents

Biodistribution; Nanotoxicity; Physico-chemical propertiesBiodistribución; Nanotoxicidad; Propiedades fisicoquímicasBiodistribució; Nanotoxicitat; Propietats fisicoquímiquesTitanium dioxide nanoparticles (TiO2 NPs) are one of the main sources of the nanoparticulate matter exposure to humans. Although several studies have demonstrated their potential toxic effects, the real nature of the correlation between NP properties and their interaction with biological targets is still far from being fully elucidated. Here, engineered TiO2 NPs with various geometries (bipyramids, plates, and rods) have been prepared, characterized and intravenously administered in healthy mice. Parameters such as biodistribution, accumulation, and toxicity have been assessed in the lungs and liver. Our data show that the organ accumulation of TiO2 NPs, measured by ICP-MS, is quite low, and this is only partially and transiently affected by the NP geometries. The long-lasting permanence is exclusively restricted to the lungs. Here, bipyramids and plates show a higher accumulation, and interestingly, rod-shaped NPs are the most toxic, leading to histopathological pulmonary alterations. In addition, they are also able to induce a transient increase in serum markers related to hepatocellular injury. These results indicate that rods, more than bipyramidal and spherical geometries, lead to a stronger and more severe biological effect. Overall, small physico-chemical differences can dramatically modify both accumulation and safety.This research was funded by National Key Research and Development Program of China (No. 2017FYA0205301), Projects of International Cooperation and Exchanges NSFC (No. 82020108017), National Natural Science Foundation of China (No. 82272821); MCIN/AEI (PID2019-111218RB-I00 and RYC-2017-23457) and Centro Singular De Investigación de Galicia Accreditation 2019−2022, and ED431G 2019/03. Moreover, parts of this work were funded by the Cluster of Excellence ‘Advanced Imaging of Matter’ of the Deutsche Forschungsgemeinschaft (DFG)-EXC 2056-project ID 390715994; by Deutscher Akademischer Austauschdienst (DAAD); and by an Alexander von Humboldt fellowship. G.S. is supported by the Italian Association for Cancer Research (AIRC), grants 22820 and 22737. NGB and VP receive financial support from the Spanish Ministerio de Ciencia, Innovación y Universidades (MCIU) (RTI2018-099965-B-I00, AEI/FEDER, UE) proyectos de I + D + i de programación conjunta internacional MCIN/AEI (CONCORD, PCI2019-103436), co-funded by the European Union. P.B. is supported by the CONCORD project (EuroNanoMed III)

Immature Spinal Locomotor Output in Children with Cerebral Palsy

Cappellini G, P. Ivanenko Y, Martino G, et al. Immature Spinal Locomotor Output in Children with Cerebral Palsy. Frontiers in Physiology. 2016;7:478