1,721,019 research outputs found
I diritti fondamentali degli stranieri tra discrezionalità del legislatore e sindacato costituzionale
No full textLe politiche regionali di integrazione degli immigrati e la questione dei Centri di identificazione ed espulsione in Liguria
No full textNeurosensory Alterations in Retinopathy of Prematurity: A Window to Neurological Impairments Associated to Preterm Birth
Full text linkRetinopathy of prematurity (ROP) is one of the main blinding diseases affecting preterm newborns and is classically considered a vascular disorder. The premature exposure to the extrauterine environment, which is hyperoxic in respect to the intrauterine environment, triggers a cascade of events leading to retinal ischemia which, in turn, makes the retina hypoxic thus setting off angiogenic processes. However, many children with a history of ROP show persistent vision impairment, and there is evidence of an association between ROP and neurosensory disabilities. This is not surprising given the strict relationship between neuronal function and an adequate blood supply. In the present work, we revised literature data evidencing to what extent ROP can be considered a neurodegenerative disease, also taking advantage from data obtained in preclinical models of ROP. The involvement of different retinal cell populations in triggering the neuronal damage in ROP was described along with the neurological outcomes associated to ROP. The situation of ROP in Italy was assessed as well
Somatostatin coupling to adenylyl cyclase activity in the mouse retina
No full textThe peptide somatostatin-14 (SRIF) acts in the mammalian retina through its distinct receptors (sst(1-5)). Scarce information is available on SRIF function in the retina, including the elucidation of transduction pathways mediating SRIF action. We have investigated SRIF and SRIF receptor modulation of adenylyl cyclase (AC) activity in both wild-type (WT) retinas and sst1 or sst2 knock-out (KO) retinas, which are known to over-express sst2 or sst1 receptors respectively. In WT retinas, application of SRIF compounds does not affect forskolin-stimulated AC activity. In contrast, activation of sst1 or sst2 receptors inhibits AC in the presence of sst2 or sst1 receptor antagonists respectively. Results from sst1 KO retinas demonstrate that either SRIF or the sst2 receptor preferring agonist octreotide, pertussis toxin-dependently inhibit AC activity. In contrast, in sst2 KO retinas, neither SRIF nor CH-275, an sst1 receptor agonist, are found to influence AC activity. As revealed by immunoblotting experiments, in sst1 KO retinas, levels of G(o)alpha proteins are 60% higher than in WT retinas and this increase in G(o)alpha protein levels is concomitant with an increase in sst2A receptor expression. We conclude that interactions between sst1 and sst2 receptors may prevent SRIF effects on AC activity. In addition, we suggest that the density of sst2 receptors and/or G(o)alpha proteins may represent the rate-limiting factor for the sst2 receptor-mediated inhibition of AC
β3-adrenergic receptor activity modulates melanoma cell proliferation and survival through nitric oxide signaling.
No full textWe have recently shown in B16F10 melanoma cells that blockade of β3-adrenergic receptors (β3-ARs) reduces cell proliferation and induces apoptosis, likely through the involvement of nitric oxide (NO) signaling. Here, we tested the hypothesis that the effects of β3-AR blockade on melanoma cells are mainly mediated by a decrease in the activity of the NO pathway, possibly due to reduced expression of inducible NO synthase (iNOS). B16F10 cells were used. Nitrite production, iNOS expression, cell proliferation, and apoptosis were evaluated. β3-AR blockade with L-748,337 reduced basal nitrite production, while β3-AR stimulation with BRL37344 increased it. The effects of β3-AR blockade were prevented by NOS activation, while the effects of β3-AR activation were prevented by NOS inhibition. Treatments increasing nitrite production also increased iNOS expression, while treatments decreasing nitrite production reduced iNOS expression. Among the different NOS isoforms, experiments using L-748,337 or BRL37344 with activators or inhibitors targeting specific NOS isoforms demonstrated a prominent role of iNOS in nitrite production. β3-AR blockade decreased cell proliferation and induced apoptosis, while β3-AR activation had the opposite effects. The effects of β3-AR blockade/activation were prevented by iNOS activation/inhibition, respectively. Taken together, these results demonstrate that iNOS-produced NO is a downstream effector of β3-ARs and that the beneficial effects of β3-AR blockade on melanoma B16F10 cell proliferation and apoptosis are functionally linked to reduced iNOS expression and NO production. Although it is difficult to extrapolate these data to the clinical setting, the targeted inhibition of the β3-AR-NO axis may offer a new therapeutic perspective to treat melanomas
Effects of Topical Gabapentin on Ocular Pain and Tear Secretion
Full text linkNeuropathic ocular pain is a frequent occurrence in medium to severe dry eye disease (DED). Only palliative treatments, such as lubricants and anti-inflammatory drugs, are available to alleviate patients’ discomfort. Anesthetic drugs are not indicated, because they may interfere with the neural feedback between the cornea and the lacrimal gland, impairing tear production and lacrimation. Gabapentin (GBT) is a structural analog of gamma-amino butyric acid that has been used by systemic administration to provide pain relief in glaucomatous patients. We have already shown in a rabbit model system that its topic administration as eye drops has anti-inflammatory properties. We now present data on rabbits’ eyes showing that indeed GBT given topically as eye drops has analgesic but not anesthetic effects. Therefore, opposite to an anesthetic drug such as oxybuprocaine, GBT does not decrease lacrimation, but–unexpectedly–even stimulates it, apparently through the upregulation of acetylcholine and norepinephrine, and by induction of aquaporin 5 (AQP5) expression in the lacrimal gland. Moreover, data obtained in vitro on a primary human corneal epithelial cell line also show direct induction of AQP5 by GBT. This suggests that corneal cells might also contribute to the lacrimal stimulation promoted by GBT and participate with lacrimal glands in the restoration of the tear film, thus reducing friction on the ocular surface, which is a known trigger of ocular pain. In conclusion, GBT is endowed with analgesic, anti-inflammatory and secretagogue properties, all useful to treat neuropathic pain of the ocular surface, especially in case of DED
β-Adrenoceptors as drug targets in melanoma: novel preclinical evidence for a role of β3 -adrenoceptors.
No full textStress plays a role in tumourigenesis through catecholamines acting at β-adrenoceptors including β1-,β2- and β3-adrenoceptors, and the use of β-adrenoceptor antagonists seems to counteract tumour growth and progression. Preclinical evidence and meta-analysis data demonstrate that melanoma shows a positive response to β-adrenoceptor blockers and in particular to propranololacting mainly at β1-and β2-adrenoceptors. Although evidence suggesting that β3-adrenoceptors may play a role as a therapeutic target in infantile haemangiomas has been recently reviewed, a comprehensive analysis of the data available from preclinical studies supporting a possible role of β3-adrenoceptors in melanoma was not available. Here, we review data from the literaturedemonstrating that propranolol may be effective at counteracting melanoma growth, and we provide preclinical evidence that β3-adrenoceptors may also play a role in the pathophysiology of melanoma, thus opening the door for further clinical assays trying to explore β3-adrenoceptor blockers as novel alternatives for its treatment
Produrre l’Alterità, fare l’Europa. Dinamiche sociotecniche nella gestione delle frontiere europee
No full textStoricamente, i flussi di informazioni sulla popolazione hanno contribuito alla formazione del più potente assemblaggio sociotecnico per la gestione della conoscenza: lo stato-nazione. Mutatis mutandis, in che modo le infrastrutture di dati contemporanee per il processamento di popolazioni non europee danno forma alla costruzione europea?
Cercando di rispondere a questa domanda che informa il più ampio progetto “Processing Citizenship” finanziato dal Consiglio Europeo della Ricerca, il capitolo presenta una duplice argomentazione. In primo luogo, dimostra la performatività delle pratiche di identificazione e registrazione di popolazioni in movimento ai confini europei: lungi dall’essere semplicemente “rappresentate,” le persone che cercano di attraversare i confini europei vengono prodotte, “portate in esistenza” (i.e., enacted) secondo modalità specifiche, spesso depotenzianti. In secondo luogo, il capitolo dimostra come le infrastrutture informative contemporanee per la produzione delle persone in movimento come “Altro” modellano l’ordine europeo.
Nel fare questo, il capitolo introduce il concetto di “produzione dell’alterità” (i.e., alterity processing) come un campo di indagine interessato sia alla gestione dell’alterità che alla costruzione infrastrutturale dell’ordine istituzionale europeo. Sulla base dei dati raccolti negli hotspot coinvolti nelle procedure di registrazione e identificazione nel Mar Mediterraneo, nonché dei documenti di progettazione delle architetture dei dati, il capitolo suggerisce che le pratiche istituzionali, i (meta)dati e le infrastrutture progettate per rendere persone sconosciute identità leggibili co-producono migranti e istituzioni. Nelle conclusioni, l’analisi sostiene la necessità di adottare uno sguardo sociotecnico per comprendere l’integrazione infrastrutturale dell’Europa
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