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Nicotinamide phosphoribosyltransferase (NAMPT) is a key enzyme involved in the recycling of nicotinamide to maintain adequate NAD levels inside the cells. It has been postulated to be a pharmacological target, as it is overexpressed in cancer cells as well as in inflammatory diseases. We describe the synthesis and characterization of a novel class of one-digit nanomolar NAMPT inhibitors based on in vitro characterization. The most active compound tested, 30c, displayed activity in xenograft and allograft models, strengthening the potential of NAMPT inhibitors as antitumoral drugs. Furthermore, in the present contribution we describe the ability of 30c to significantly improve the outcome of colitis in mice. Given that this is the first report of an effect of NAMPT inhibitors in colitis, this result paves the way for novel applications for this class of compounds.

Background: Fencers often complain of progressive difficulty in breathing during matches, which is generally attributed to restricted air, light and heat circulation from wearing a mask. Physiologically, the nasal structure generates airflow resistance that can reach -50% of the total respiratory resistance., Objectives: This study aims to investigate the presence of nasal obstruction in fencers and the relationship with the use of mask., Materials and Methods: An observational study on 40 fencers (18 males, 22 females) was conducted. Fencers perform a usual assault, wearing the mask and standardized physical exercises (running, sprints and obstacles) without the mask. ENT examination with a nasal flexible fiberscope, Anterior Active Rhinomanometry (AAR) and Peak Nasal Inspiratory Flow (PNIF) measurement before and after physical activity with or without the mask was recorded., Results: Before physical exercise, the total nasal airway resistance mean value for AAR was 0.33 ± 0.17 Pa/cm(3)/s at 150 Pa. After a match with the mask, the mean value was 0.28 ± 0.16 Pa/cm(3)/s. After normal physical exercises without mask, the mean value was 0.24 ± 0.15 Pa/cm(3)/s. Using t tests, statistically significant difference between nasal resistance before and after physical activity (P < 0.05) was observed, but no significant difference in nasal resistance between the basal value and that taken after a match wearing the masks (P = 0.1265). PNIF values significantly increase with exercise (P < 0.05)., Conclusions: Our study shows that wearing the mask causes increased breathing impairment in fencers, when compared with similar physical activity without the mask.

Tumorigenesis in human glioblastoma multiforme (GBM) is driven by several genetic abnormalities with disruption of important molecular pathways, such as p53/MDM2/p14ARF and EGFR/PTEN/Akt/mTOR. The malignant progression of human GBM is also primarily associated with a peculiar multistep pathophysiological process characterized by intratumoral ischemic necrosis (i.e. pseudopalisading necrosis) and activation of the hypoxia-inducible factor (HIF)-1alpha pathway with consequent peritumoral microvascular proliferation and infiltrative behaviour. Predictable preclinical animal models of GBM should recapitulate the main pathobiological hallmarks of the human disease. In this study we describe two murine orthotopic xenograft models using U87MG and U251 human cell lines. Ten Balb/c nude male mice were orthotopically implanted with either U87MG (5 mice) or U251 (5 mice) cell lines. Intracranial tumor growth was monitored through Magnetic Resonance Imaging (MRI). Immunohistopathological examination of the whole cranium was performed 30 days after implantation. U251 orthotopic xenografts recapitulated the salient pathobiological features described for human GBM, including invasive behaviour, wide areas of pseudopalisading necrosis, florid peripheral angiogenesis, GFAP and vimentin expression, nonfunctional p53 expression, striking active-caspase-3 and HIF-1alpha expression along pseudopalisades. U87MG orthotopic xenografts proved to be very dissimilar from human GBM, showing expansile growth, occasional necrotic foci without pseudopalisades, intratumoral lacunar pattern of angiogenesis, lack of GFAP expression, functional p53 expression and inconsistent HIF-1alpha expression. Expression of pAkt was upregulated in both models. The results obtained suggest that the U251 orthotopic model may be proposed as a predictive and reliable tool in preclinical studies since it recapitulates the most salient pathobiological features reported for human GBM.

Study aimed principally at applying the data recently gathered with regard to Bronchial Reactivity to rhinology, with special regard to non-atopic or allergic hyperresponsiveness. In the past decade, Ultrasonic Nebulized Distilled Water (U.N.D.W.) was recognized as one of the best test in Bronchial Reactivity. In allergic and non-allergic rhinitis, the Authors tried to use U.N.D.W. to reproduce symptoms of rhinitis. Results show that U.N.D.W. could be included in the Nasal Hyperreactivity test. Secondly, but not less interesting, is the prevention of experimental rhinitis with U.N.D.W. by using Furosemide, a diuretic administered by inhalation. The prevention of Ca++ penetration into nasal cell can block any mediator-activation. Such procedure may be applied in polyposis after surgery in order to prevention recurrence, data show the complete applicability of this pharmacological treatment in children as well.