Mettere a fuoco il mondo. Conversazioni sulla filosofia di Achille Varzi

International audienc

Intravitreal NGF administration counteracts retina degeneration after permanent carotid artery occlusion in rat

<p>Abstract</p> <p>Background</p> <p>The neurotrophin nerve growth factor (NGF) is produced by different cell types in the anterior and posterior eye, exerting a neuroprotective role in the adult life. The visual system is highly sensitive to NGF and the retina and optic nerve provides suitable subjects for the study of central nervous system degeneration. The model of bilateral carotid occlusion (two-vessel occlusion, 2VO) is a well-established model for chronic brain hypoperfusion leading to brain capillary pathology, to retina and optic nerve degeneration. In order to study if a single intravitreal injection of NGF protects the retina and the optic nerve from degeneration during systemic circulatory diseases, we investigated morphological and molecular changes occurring in the retina and optic nerve of adult rats at different time-points (8, 30 and 75 days) after bilateral carotid occlusion.</p> <p>Results</p> <p>We demonstrated that a single intravitreal injection of NGF (5 μg/3 μl performed 24 hours after 2VO ligation) has a long-lasting protective effect on retina and optic nerve degeneration. NGF counteracts retinal ganglion cells degeneration by early affecting Bax/Bcl-2 balance- and <it>c-jun- </it>expression (at 8 days after 2VO). A single intravitreal NGF injection regulates the demyelination/remyelination balance after ischemic injury in the optic nerve toward remyelination (at 75 days after 2VO), as indicated by the MBP expression regulation, thus preventing optic nerve atrophy and ganglion cells degeneration. At 8 days, NGF does not modify 2VO-induced alteration in VEFG and related receptors mRNA expression.</p> <p>Conclusion</p> <p>The protective effect of exogenous NGF during this systemic circulatory disease seems to occur also by strengthening the effect of endogenous NGF, the synthesis of which is increased by vascular defect and also by the mechanical lesion associated with NGF or even vehicle intraocular delivery.</p

Novel understanding on genetic mechanisms of enteric neuropathies leading to severe gut dysmotility

The enteric nervous system (ENS) is the third division of the autonomic autonomic nervous system and the largest collection of neurons outside the central nervous system (CNS). The ENS has been referred to as "the brain in the gut" or "the second brain of the human body" because of its highly integrated neural circuits controlling a vast repertoire of gut functions, including absorption/secretion, splanchnic blood vessels, some immunological aspects, intestinal epithelial barrier, and gastrointestinal (GI) motility. The latter function is the result of the ENS fine-tuning over smooth musculature, along with the contribution of other key cells, such as enteric glia (astrocyte like cells supporting and contributing to neuronal activity), interstitial cells of Cajal (the pacemaker cells of the GI tract involved in neuromuscular transmission), and enteroendocrine cells (releasing bioactive substances, which affect gut physiology). Any noxa insult perturbing the ENS complexity may determine a neuropathy with variable degree of neuro-muscular dysfunction. In this review, we aim to cover the most recent update on genetic mechanisms leading to enteric neuropathies ranging from Hirschsprung's disease (characterized by lack of any enteric neurons in the gut wall) up to more generalized form of dysmotility such as chronic intestinal pseudo-obstruction (CIPO) with a significant reduction of enteric neurons. In this line, we will discuss the role of the RAD21 mutation, which we have demonstrated in a family whose affected members exhibited severe gut dysmotility. Other genes contributing to gut motility abnormalities will also be presented. In conclusion, the knowledge on the molecular mechanisms involved in enteric neuropathy may unveil strategies to better manage patients with neurogenic gut dysmotility and pave the way to targeted therapies

Medium Resolution 0.97-5.3 micron spectra of Very Young Benchmark Brown Dwarfs with NIRSpec onboard the James Webb Space Telescope

Spectra of young benchmark brown dwarfs with well-known ages are vital to characterize other brown dwarfs, for which ages are in general not known. These spectra are also crucial to test atmospheric models which have the potential to provide detailed information about the atmospheres of these objects. However, to optimally test atmospheric models, medium-resolution, long-wavelength coverage spectra with well-understood uncertainties are ideal, such as the spectra provided by the NIRSpec instrument onboard the James Webb Space Telescope. In this paper, we present the medium-resolution JWST/NIRSpec spectra of two young brown dwarfs, TWA 28 (M9.0) and TWA 27A (M9.0), and one planetary-mass object, TWA 27B (L6.0), members of the TW Hydrae Association (~10 Myr). We show the richness of the atomic lines and molecular bands present in the spectra. All objects show signs of a circumstellar disk, via near-infrared excess and/or via emission lines. We matched a set of cloudless atmospheric spectra (ATMO), and cloudy atmospheric spectra (BT-Settl) to our NIRSpec spectra, and analyzed which wavelength ranges and spectral features both models reproduce best. Both models derive consistent parameters for the three sources, and predict the existence of CH4 at 3.35 microns in TWA 27B. Nonetheless, in contrast to other slightly older objects with similar spectral type, like PSO 318.5-22 and VHS 1256b, this feature is not present in the spectrum of TWA 27B. The lack of the CH4 feature might suggest that the L/T transition of very young dwarfs starts at later spectral types than for older brown dwarfs.Comment: Accepted in A

Comparative in vitro and ex vivo studies on the bactericidal activity of Tetraclean, a new generation endodontic irrigant, and sodium hypochlorite

The aim of this study was to compare the efficacy of a new generation endodontic irrigant, Tetraclean, to the widely used sodium hypochlorite. Tetraclean combines a powerful detergent effect with a strong antimicrobial efficacy, whereas sodium hypochlorite has several drawbacks and is sometimes ineffective in preventing microbial-mediated endodontic failure. The bactericidal activity of both irrigants against Enterococcus faecalis, the most commonly isolated species from root canals of teeth with post-treatment disease, was assessed i) in vitro, according to the European Standard lines for the evaluation of the bactericidal activity of chemical disinfectants, and ii) with an ex vivo model of extracted and decoronated human teeth, infected with E. faecalis and subsequently irrigated with either of the irrigants. Both irrigants display very similar bactericidal activity against E. faecalis in vitro. However, the ex vivo model shows that only in the teeth irrigated with Tetraclean did the bacterial burden gradually drop until no bacteria were detectable a few days post-irrigation. Vice versa, in the teeth irrigated with sodium hypochlorite, the drop in the bacterial burden was rapid but temporary and most of the teeth were colonized again by 48 hours post-irrigation