452 research outputs found

    The endocannabinoid system: 1. Design, synthesis and biological evaluation of heterocyclic derivatives as potential MAGL inhibitors. 2. Study of the ischemic damage effects in cannabinoid receptors knockout mice.

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    My PhD thesis is about the study of different aspect of endocannabinoid system. In particular during my reserach project I focused my attention on two different topics: 1. Design, synthesis and biological evaluation of heterocyclic derivatives as potential MAGL inhibitors, which could be use for the treatment of different kind of disease, such as neurological disease, cancer, glaucoma, sclerosis etc... 2. Study of the ischemic damage effects in CB2 receptors knockout and CB1-CB2 receptors double knockout mice of both sexes

    L’INSEGNAMENTO-APPRENDIMENTO DELLA STORIA NELLA SCUOLA PLURILINGUE

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    Lo sviluppo di competenze disciplinari e competenze linguistiche procedeparallelamente nell'apprendimento della storia e avviene in una situazione didattica che è, innanzitutto, una situazione comunicativa. Partendo dall'analisi della proposta di un Documento di Riferimento per lo studio della storia, elaborata dalla Divisione delle Politiche Linguistiche del Consiglio d'Europa, l'articolo evidenzia come la scuola plurilingue sia chiamata a confrontarsi con un nuovo modo di pensare all'insegnamento-apprendimento della storia che, oltre alle conoscenze disciplinari specifiche, comprenda la situazione comunicativa in cui si realizza e i diversi luoghi del discorso, ovvero i diversi domini linguistici, generi e tipologie di testi, convocati dal sapere storico.   Discipline-specific and linguistic competences are developed in a parallel way when learning history.  Both take place in a didactic situation that is, above all, communicative. This paper analyzes the Council of Europe's Language Policy Division proposal for  guidelines regarding the study of history, focusing on how multilingual schools must address a new way of thinking about the teaching of history. In addition to the specific knowledge of the subject, the communicative situations which arise and the different areas of discourse, meaning diverse linguistic fields, genres and types of texts that make up historical sources, are investigated

    Automated and Flexible Coil Winding Robotic Framework

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    European electrical machines manufacturers need to increase the flexibility of production process, due to the high cost of equipment setup at the beginning of each new production batch. Overall, most of these European manufacturers are striving to reduce costs while preserving the quality of products, in order to face the competition by Far East companies. There is a strong need for increasing productivity, flexibility and quality. In particular, in wound coils manufacturing process, current technologies allow only to big international manufacturer to automate their production lines, due to high machinery cost and set-up time, while small and medium manufacturers are forced to direct themselves towards manual production. This work aims to reduce costs and increase flexibility with the following contributions: (1) important reduction of setup time and costs of the winding machine, thanks to the simplicity and flexibility of the proposed approach; (2) increase in the quality of the final motors, thanks to the increased amount of copper that the robot will be able to insert in each coil with respect to manual winding; (3) possibility to parallelize the winding operations, dramatically increasing production rate; (4) decreased number of defected cores, thanks to an advanced quality inspection system; (5) reduction of environmental impact of the production process, thanks to a reduction of wasted copper wire

    Design and synthesis of cannabinoid recepor ligands as potential soft drugs and as CB2 selective ligands.

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    Design and synthesis of cannabinoid receptor ligands as potential soft drugs and as CB2 selective ligands

    Effect of retinoic acid on human adrenal corticosteroid synthesis.

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    AbstractAimsRetinoic acid has recently yielded promising results in the treatment of Cushing's disease, i.e., excess cortisol secretion due to a pituitary corticotropin (ACTH)-secreting adenoma. In addition to its effect on the tumoral corticotrope cell, clinical results suggest an additional adrenal site of action. Aim of this study was to evaluate whether retinoic acid modulates cortisol synthesis and secretion by human adrenals in vitro.Main methodsPrimary cultures from 10 human adrenals specimens were incubated with 10nM, 100nM and 1μM retinoic acid with and without 10nM ACTH for 24h. Cortisol levels were measured by radioimmunoassay and CYP11A1, STAR and MC2R gene expression analyzed by real-time PCR.Key findingsRetinoic acid increased cortisol secretion (149.5±33.01%, 151.3±49.45% and 129.3±8.32% control secretion for 10nM, 100nM and 1μM respectively, p<0.05) and potentiated STAR expression (1.51±0.22, 1.56±0.15 and 1.59±0.14 fold change over baseline, for 10nM, 100nM and 1μM respectively, p<0.05). Concurrently, retinoic acid markedly blunted constitutional and ACTH-induced MC2R expression (0.66±0.11, 0.62±0.08 and 0.53±0.07 fold change over baseline, for 10nM, 100nM and 1μM respectively, p<0.05; 0.71±0.10, 0.51±0.07 and 0.51±0.08 fold change over ACTH alone, for 10nM, 100nM and 1μM respectively, p<0.05). No effect on CYP11A1 was observed.SignificanceRetinoic acid stimulates cortisol synthesis and secretion in human adrenals and at the same time markedly blunts ACTH receptor transcription. These results reveal a novel, adrenal effect of retinoic acid which may contribute to its efficacy in patients with Cushing's disease

    Resveratrol exhibits a strong cytotoxic activity in cultured cells and has an antiviral action against polyomavirus: potential clinical use

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    <p>Abstract</p> <p>Background</p> <p>Resveratrol is a non flavonoid polyphenol compound present in many plants and fruits and, at especially high concentrations, in the grape berries of <it>Vitis vinifera</it>. This compound has a strong bioactivity and its cytoprotective action has been demonstrated, however at high concentrations the drug exhibits also an effective anti-proliferative action. We recently showed its ability to abolish the effects of oxidative stress in cultured cells. In this work we assayed the bioactivity of resveratrol as antiproliferative and antiviral drug in cultured fibroblasts. Studies by other Authors showed that this natural compound inhibits the proliferation of different viruses such as herpes simplex, varicella-zoster and influenza A. The results presented here show an evident toxic activity of the drug at high concentrations, on the other hand at sub-cytotoxic concentrations, resveratrol can effectively inhibit the synthesis of polyomavirus DNA. A possible interpretation is that, due to the damage caused by resveratrol to the plasma membrane, the transfer of the virus from the endoplasmic reticulum to the nucleus, may be hindered thus inhibiting the production of viral DNA.</p> <p>Methods</p> <p>The mouse fibroblast line 3T6 and the human tumor line HL60 were used throughout the work. Cell viability and vital cell count were assessed respectively, by the MTT assay and Trypan Blue staining. Cytotoxic properties and evaluation of viral DNA production by agarose gel electrophoresis were performed according to standard protocols.</p> <p>Results</p> <p>Our results show a clear dose dependent both cytotoxic and antiviral effect of resveratrol respectively at high and low concentrations. The cytotoxic action is exerted towards a stabilized cell-line (3T6) as well as a tumor-line (HL60). Furthermore the antiviral action is evident after the phase of virion entry, therefore data suggest that the drug acts during the synthesis of the viral progeny DNA.</p> <p>Conclusion</p> <p>Resveratrol is cytotoxic and inhibits, in a dose dependent fashion, the synthesis of polyomavirus DNA in the infected cell. Furthermore, this inhibition is observed at non cytotoxic concentrations of the drug. Our data imply that cyto-toxicity may be attributed to the membrane damage caused by the drug and that the transfer of polyomavirus from the endoplasmic reticulum to the cytoplasm may be hindered. In conclusion, the cytotoxic and antiviral properties of resveratrol make it a potential candidate for the clinical control of proliferative as well as viral pathologies.</p

    Approval rating and opinion of outpatients and general practitioners toward generic drugs: a questionnaire-based real-world study

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    Purpose: Generic drugs use in the Liguria region is higher than the Italian average, but lower than in other European countries. No data exist about real-life prescription and level of awareness of generic drugs. In this study, we analyzed demographic, social, economic and cultural factors that may affect the level of awareness of generic drugs and their effective use. Methods: We conducted a population survey using a structured questionnaire, administered to a sample of 8 outpatient clinics of general practitioners located in different districts of Genoa (Liguria, Italy). Multivariate logistic modeling was adopted to study the relationship between awareness/use of generic drugs and characteristics of subjects. Results: Out of 2,000 outpatients surveyed, 95% were aware of generic drugs: these were mostly females (OR =2.2, 95% CI: 1.4\u20133.6), .35 years old (OR .6.0 vs 18\u201335 years), with a high level of education (OR .4.4 vs \u201celementary sch\u201d), living in the west side of the city (OR =1.9 vs center); of these, only 59% declared that they effectively use generic drugs. Users were younger (OR =3.1, 18\u201335 years vs .65 years), with a high level of education (high school/university degree vs no title/elementary/secondary school OR =1.7), and were aware of the lower cost compared with branded drugs, and were mainly informed by pharmacists and physicians. Conclusions: Although subjects were substantially aware of the existence of generic drugs, ~40% still did not use them; doubts about their efficacy seem to be mainly driven by the idea that cheaper drugs lead to lower product quality, in term

    Sudden, unexpected death of a 15-year-old boy due to pancarditis a case report and possible etiopathogenesis.

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    none5siOsculati, Antonio; VisonĂ , Silvia Damiana; Ventura, Francesco; Castelli, Francesca; Andrello, LuisaOsculati, ANTONIO MARCO MARIA; Visona', SILVIA DAMIANA; Ventura, Francesco; Castelli, Francesca; Andrello, Luis
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