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    Diffusely infiltrating glioma

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    Modern neuropathology serves a key function in the multidisciplinary management of brain tumor patients. Owing to the recent advancements in molecular neurooncology, the neuropathological assessment of brain tumors is no longer restricted to provide information on a tumor’s histological type and malignancy grade, but may be complemented by a growing number of molecular tests for clinically relevant tissue-based biomarkers

    Neuropharmacology and behavior in planaria: translations to mammals

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    Planarians are the simplest animals to exhibit a body plan common to all vertebrates and many invertebrates, characterized by bilateral rather than radial symmetry, dorsal and ventral surfaces, and a rostrocaudal axis with a head and a tail, including specialized sense organs and an aggregate of nerve cells in the head. Neurons in planarian more closely resemble those of vertebrates than those of advanced invertebrates, exhibiting typical vertebrate features of multipolar shape, dendritic spines with synaptic boutons, a single axon, expression of vertebrate-like neural proteins, and relatively low spontaneously generated electrical activity. Here we report the most relevant contribution to the knowledge of the neuropharmacology of planarians, with particular reference to the behavioral consequences of the exposure to drugs acting on neural transmission. Neurochemical and histochemical data indicate the presence of several neurotransmitter-receptor systems in planarians. Moreover, a variety of experimental studies characterized specific behavioral patterns of these animals following the exposure to drugs acting on neural transmission. There is also evidence of the interactions between discrete neurotransmitter-receptor systems in modulating behavior in planarians. Finally, the model has proved efficacy for investigating the neurotoxicology of the dopamine neurons, and for the initial screening of the neuroprotective potential of drugs. In conclusion, these findings indicate that interactions between discrete neurotransmitter-receptor systems occur very early along phylogeny, although they may have evolved from very fundamental behaviors, such as motor activity in planarian, to more complex and integrated functions in vertebrates

    Acetilcholine/dopamine interaction in planaria

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    Planaria represents the most primitive example of centralization and cephalization of nervous system. Previous reports indicate that planaria shows specific behavioral patterns, analogous to mammalian stereotypes, in response to drugs acting on acetylcholine or dopamine transmission. Here we further characterized these responses, and investigated the interactions between cholinergic and dopaminergic systems by means of behavioral methods. Exposure to cholinergic agonists physostigmine or nicotine produced hypokinesia with 'bridge-like' and 'walnut' positions, respectively. Blockade of muscarinic receptors by atropine produced 'screw-like' hyperkinesia. Exposure to dopamine agonists (nomifensine, apomorphine) produced marked hyperkinesia with 'screw-like' movements. Finally, exposure to dopamine antagonists produced immobility or 'bridge-like' position. Pre-exposure to physostigmine blocked the behavioral effects of nomifensine and reduced and markedly delayed the behavioral effects of apomorphine. Pre-exposure to apomorphine slightly reduced and delayed the behavioral changes by physostigmine. Finally, planaria exposed to atropine after either SCH23388 or sulpiride showed 'C-like' or 'screw-like' hyperkinesia, respectively. Thus, reduction of cholinergic transmission seems to play a pivotal role in determining hyperkinesia in planaria. Under these conditions, different patterns of hyperkinetic activities occur, according to the subpopulation of dopamine receptors stimulated by drugs. These findings suggest that interactions between cholinergic and dopaminergic systems occur very early in animal phylogeny

    Protezione sismica di edifici esistenti in c.a. con controventi dissipativi in acciaio

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    l presente volume, incentrato sull’adeguamento sismico di edifici esistenti in cemento armato attraverso l’utilizzo di controventi dissipativi in acciaio, intende fornire un utile strumento pratico rivolto ai professionisti, su un tema di imprescindibile importanza per il patrimonio costruito italiano e tuttavia scarsamente approfondito e trattato a livello accademico e nella pratica professionale. Sebbene i codici normativi vigenti per gli edifici in zona sismica contengano indicazioni sull’adeguamento del costruito attraverso interventi innovativi quali i sistemi di isolamento alla base, l’utilizzo di controventi dissipativi inseriti all’interno degli edifici esistenti risulta un argomento poco approfondito e trattato. L’opera è suddivisa nei seguenti capitoli che trattano in modo completo ed esaustivo la protezione degli edifici in c.a.: Ipotesi generali e requisiti generali prestazionali di una costruzione in c.a.; Valutazione della capacità sismica di edifici esistenti in c.a.; Dispositivi per la dissipazione di energia; Miglioramento della risposta al sisma con controventi dissipativi; Esempio applicativo: adeguamento sismico di un edificio in c.a. di 6 piani fuori terra mediante l’utilizzo di controventi dissipativi. La monografia Protezione sismica di edifici esistenti in c.a. con controventi dissipativi in acciaio è distribuita in Italia quale undicesimo volume della collana “Acciaio” edita da Fondazione Promozione Acciaio e curata dalla Commissione Sismica per le Costruzioni in Acciaio. Dal 2008 la Fondazione fornisce al professionista una serie di pubblicazioni tecniche dedicate alla progettazione in acciaio aggiornate alle più recenti normative. Fanno parte della medesima collana: Acciai strutturali, prodotti e sistemi di unione, Analisi di una soluzione monopiano con il metodo plastico, Edifici monopiano in acciaio ad uso industriale, Progettazione di strutture in acciaio secondo le NTC e gli Eurocodici –basi concettuali ed esempi di calcolo, Progettazione di strutture composte acciaio – calcestruzzo secondo gli Eurocodici e le Norme Tecniche per le Costruzioni, Collegamenti in acciaio in edifici monopiano e multipiano – Eurocodice 3, Progettazione di giunzioni e strutture tubolari in acciaio, I pannelli coibentati in acciaio nella progettazione e realizzazione di strutture e involucro, Verifica e progetto di aste in acciaio – sforzo normale, flessione semplice e composta e Guida all’architettura multipiano in acciaio – manuale tecnico pratico. Il nostro auspicio è che la collana “Acciaio” possa contribuire ad una maggiore conoscenza delle opere in acciaio, capaci di distinguersi per gli elevati standard qualitativi oltre ad altri importanti vantaggi quali la sostenibilità ambientale, la rispondenza ai requisiti di antisismicità, la funzionalità, le potenzialità architettoniche, la rapidità costruttiva e la semplicità di messa in opera Consapevole che in Italia le quote di mercato delle costruzioni in acciaio sono molto inferiori rispetto alla media europea, principalmente per la limitata conoscenza del materiale e delle sue peculiarità, FPA si impegna nel promuovere costantemente la cultura dell’acciaio presso il proprio target di riferimento, costituito da professionisti e studi di progettazione, imprese di costruzione, committenti pubblici e privati, senza dimenticare di rivolgere uno sguardo al futuro, dedicando molta attenzione all’insegnamento nelle università. Attraverso il sostegno dei maggiori produttori d’acciaio italiani ed europei e di altri importanti rappresentanti della filiera tra cui trasformatori, centri di servizio, costruttori metallici e progettisti, uniti nello scopo di promuovere l’impiego dell’acciaio nelle costruzioni ed infrastrutture, la Fondazione pone al servizio degli operatori del settore delle costruzioni italiano le competenze tecniche e scientifiche dei Soci, sviluppando un’azione costante di comunicazione ed informazione a supporto dei professionisti, degli studenti universitari, dei committenti pubblici e privati, sulle possibilità e i vantaggi offerti dalle soluzioni in acciaio. La Fondazione Promozione Acciaio è attiva nel settore delle costruzioni e infrastrutture in acciaio attraverso quattro commissioni tecniche: Commissione Sismica per le Costruzioni in Acciaio, Commissione per la Sicurezza delle Costruzioni in Acciaio in caso d’Incendio, Commissione per le Costruzioni in Acciaio Ecosostenibili, Gruppo di lavoro Normative, che toccano temi prioritari per le costruzioni metalliche: l’efficienza dell’acciaio in zona sismica, la sicurezza di fronte all’incendio, la sostenibilità del materiale e le nuove responsabilità introdotte dalla normativa di settore. Le commissioni hanno un ruolo di primo piano nell’insegnamento e nella promozione delle soluzioni costruttive in acciaio, curando la realizzazione delle predette monografie tecniche e l’organizzazione di qualificati corsi di formazione oltre al costante aggiornamento del portale www.promozioneacciaio.it. FPA è anche un Ufficio Tecnico che fornisce assistenza tecnica, scientifica e normativa a chi già sviluppa e progetta costruzioni metalliche o anche solo a chi desidera ampliare le proprie conoscenze professionali. I ringraziamenti da parte di Fondazione Promozione Acciaio vanno agli autori del volume, prof. Franco Braga, ing. Francesca Buttarazzi, prof. Andrea Dall’Asta e prof. Walter Salvatore; si desiderano inoltre ringraziare coloro che hanno contribuito alla realizzazione dei singoli capitoli: Silvia Caprili, Giuseppina Conti, Francesco Morelli, Laura Ragni, Enrico Tubaldi. Un ringraziamento va inoltre ai Soci della Fondazione, per il costante supporto verso la mission di FPA: la diffusione e la divulgazione della cultura del progettare e del costruire in acciaio

    Effects of intra-VTA injection of neurotensin on local cerebral glucose utilization in the rat.

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    The [14C]2-deoxyglucose method was applied to measure the effects of the injection of neurotensin (7 microg) in the ventral tegmental area on local cerebral glucose utilization in the rat. Injection of neurotensin produced significant increases of glucose utilization in the shell of the nucleus accumbens and in the olfactory tubercle. These results indicate that stimulation of neurotensin receptors in the ventral tegmental area produces functional changes that are confined to the regions receiving mesolimbic projections within the rostral extended amygdaloid complex. These findings extend our understanding on the effects of neurotensin in the limbic system, with particular regard to reward pathways

    Cannabinoid-induced stimulation of motor activity in planaria by an opioid receptor-mediated mechanism

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    Planaria, the most primitive example of centralization and cephalization of the nervous system along phylogeny, shows specific stereotyped behavioral patterns following exposure to drugs acting on neural transmission. In this study, the authors investigated the effects of exposure to the synthetic cannabinoid receptor agonist WTN55212.2 on motor activity in planaria. WTN55212.2 produced dose-dependent stimulation of motor behavior. High doses of the drug caused stereotyped activities identical to those seen previously with opioid agonists. These effects were antagonized by coexposure to cannabinoid or opioid receptor antagonists. The results indicate that functional interactions between cannabinoid and opioid systems are highly conserved along phylogeny, at least at the behavioral level

    Dopamine transporter immunoreactivity in peripheral blood mononuclear cells in amyotrophic lateral sclerosis

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    Amyotrophic lateral sclerosis (ALS) is a chronic progressive neuromuscular disorder of unknown etiology, characterized by weakness, muscle wasting, fasciculations, and increased reflexes, with conserved intellect and higher functions. The neuropathology of ALS is mostly confined to damage of the motor neurons in the cerebral cortex, some motor nuclei of the brainstem, and anterior horns of the spinal cord. However, there is evidence for the involvement of other neuronal systems in the disease. In particular, damage of the dopamine neurons has been shown by neurochemical and imaging studies in the brain and spinal cord of ALS patients. Recent reports suggest that peripheral blood mononuclear cells (PBMC) may represent a useful in vivo model to study neurochemical alterations that occur in neurodegenerative disorders. Here we demonstrate the significant reduction of dopamine transporter immunoreactivity in PBMC of patients affected by ALS with respect to healthy subjects. These results extend our knowledge of damage of the dopamine system in ALS to peripheral cells. Thus, the original concept of ALS as an isolated degeneration of motor neurons seems to extend to a more widespread understanding of the disease with involvement of other neuronal systems in the central as well as peripheral nervous system

    FSTL5 expression is a marker of Group C metastatic medulloblastomas

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    INTRODUCTION: Medulloblastoma (MB) is the most commonmalignant brain tumor in children. Four different molecular subgroups are recognized, which differ in gene expression, genomic aberrations, histology, demographics and survival:WNT and SHH groups, having specific mutations in the homonymous pathway, and groups C and D having several genetic alternations not specific to a single pathway. The gene for follistatin-like protein 5, FSTL5, is overexpressed in nonSHH/nonWNT MBs poorly characterized. Highexpression of FSTL5 is significantly associated with reduced event-free and overall survival in non-WNT/non-SHHMBs. The major aim of this project is to study the FSTL5 expression level in pediatric MBs with metastasis at the onset. METHOD: We investigated the protein expression of biomarkers involved in metastatic pathways by IHC and FSTL5 expression level by RT-PCR in 26 metastatic MBs samples and correlated these data with the outcomes by Kaplan-Meier statistic analysis. RESULTS: 83% of Group C MBs showed high level of FSTL5 while none of these presented down-expression. Low-expression level of FSTL5 was find in 60% of SHH MBs and none showed over-expression. Kaplan-Meier test revealed that, in our cohort, highexpression ofFSTL5didnot correlatewithworse outcomewhile lowexpression of FSTL5 was associated with good prognosis and the co-presence of FSTL5 with other biomarkers correlated with poorer prognosis. CONCLUSION: FSTL5 is a marker of Group C in medulloblastomas with metastasis at the onset and the results highlighted decreased FSTL5 expression as a marker of good prognosis. Group C MBs have characteristic molecular features that confirm the poorest outcome also inMBs with metastasis at the onset

    The Dopaminergic System in Peripheral Blood Lymphocytes: From Physiology to Pharmacology and Potential Applications to Neuropsychiatric Disorders

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    Besides its action on the nervous system, dopamine (DA) plays a role on neural-immune interactions. Here we review the current evidence on the dopaminergic system in human peripheral blood lymphocytes (PBL). PBL synthesize DA through the tyrosine-hydroxylase/DOPA-decarboxylase pathway, and express DA receptors and DA transporter (DAT) on their plasma membrane. Stimulation of DA receptors on PBL membrane contributes to modulate the development and initiation of immune responses under physiological conditions and in immune system pathologies such as autoimmunity or immunodeficiency. The characterization of DA system in PBL gave rise to a further line of research investigating the feasibility of PBL as a cellular model for studying DA derangement in neuropsychiatric disorders. Several reports showed changes of the expression of DAT and/or DA receptors in PBL from patients suffering from several neuropsychiatric disorders, in particular parkinsonian syndromes, schizophrenia and drug-or alcohol-abuse. Despite some methodological and theoretical limitations, these findings suggest that PBL may prove a cellular tool with which to identify the derangement of DA transmission in neuropsychiatric diseases, as well as to monitor the effects of pharmacological treatments
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