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Specific and effective preventive treatment for diabetic retinopathy (DR) is presently unavailable, mostly because the early stages of the complication have been, until recently, poorly understood. The recent demonstration that the vascular phase of DR is preceded and possibly caused by the neurodegeneration of retinal ganglion cells suggests that DR could, at least theoretically, be prevented through an early neuroprotective approach. The aims of our study were to clarify the natural history of diabetes-driven retinal neurodegeneration and to verify the possibility to prevent DR using topical nerve growth factor (NGF). The results of the study show that retinal neurodegeneration, characterized by the loss of retinal ganglion cells represents a relatively early phenomenon of diabetes (between 5 and 16 weeks of age), which tends to be self-limiting in the long run. Neurodegeneration is followed by the development of DR-related vascular dysfunctions, as confirmed by the development of acellular capillaries and the loss of retinal pericytes. Both retinal neurodegeneration and subsequent vascular dysfunction can be successfully prevented by topical NGF administration. These findings suggest that: 1) The first stage of DR consists in a self-limiting retinal neurodegeneration 2) The demonstrated effectiveness of topical NGF in the prevention of DR could be rapidly translated into clinical practice.

The binding selectivity of charged liposomes to the spinal cord of rats affected by experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, was investigated. Positively and negatively charged liposomes were injected into the tail vein of rats, and blood/brain barrier (BBB) targeting was determined by confocal microscopy as a function of the temporal evolution of the inflammatory response. Accumulation in spinal cord endoneural vessels was observed for cationic, but not for anionic, liposomes, and only in EAE but not in healthy rats. The overall binding efficacy paralleled the severity of the clinical score, but targeting was observed already before clinical manifestation of inflammation. Preferential binding of positively charged liposomes in the course of acute EAE can be ascribed to subtle changes of BBB morphology and charge distribution in a similar way as for the binding of cationic particles to proliferating vasculature in chronic inflammation and angiogenesis. Our findings suggest that vascular changes related to increased binding affinity for cationic particles are very early events within the inflammatory reaction in acute EAE. Investigation of cationic vascular targeting can help to shed further light on these occurrences, and, potentially, new diagnostic and therapeutic options may become available. In neuroinflammatory diseases, cationic colloidal carrier particles may enable intervention at affected BBB by an approach which is independent from permeability increase. © 2009 American Chemical Society.

Lo spazio geografico è rilevante per lo sviluppo di nuovi prodotti e per le dinamiche innovative delle imprese poiché la diffusione di conoscenza, soprattutto quella tacita, è favorita dalla prossimità territoriale e dall’ispessimento di relazioni che richiedono tempo e occasioni comuni. La globalizzazione dei mercati e la concentrazione geografica delle specializzazioni tecnologiche, tuttavia, non consentono di limitare ai confini locali l’estensione delle reti tra i soggetti dell’innovazione; a tutti i livelli, il grado di apertura esterna dei sistemi condiziona notevolmente la capacità di assorbire e generare nuove conoscenze. Si impone perciò l’adozione di forme organizzative che meglio si adattino al cambiamento ed emerge il ruolo decisivo di intermediari che facilitino le relazioni e il trasferimento di competenze tecnologiche e manageriali. Che cosa significa questo in concreto? Significa stabilire i compiti dei vari nodi della rete sulla base dell’inventario esplicito dei tipi di intelligenze in gioco, concordando a priori la finalizzazione che si darà alla rete stessa. Il libro, dopo aver discusso le caratteristiche e i confini dei sistemi di innovazione, illustra il ruolo dei vari nodi, le imprese, i centri di ricerca, le istituzioni, con particolare riferimento ai fornitori di servizi pubblici locali e alle attività brevettuali. Il territorio di riferimento per lo studio è l’Abruzzo, dove da tre anni è stato fondato il Polo di innovazione ICT, con il compito specifico di sostenere il sistema locale di innovazione.

OBJECTIVE: The appropriateness of the 1-in-X numerical format to convey quantitative medical probabilities is currently under discussion because of its distortive effect on subjective probability assessment. Previous research, however, always asked participants to imagine a hypothetical scenario. The aim of the present research is to support the existence of the 1-in-X effect in a real setting: when pregnant women have to evaluate their personal risk of Down syndrome according to their maternal age. METHOD: During the first prenatal visit, pregnant women were asked to evaluate their own risk of having a child with Down syndrome according to their age, when such risk was presented either in the 1-in-X or in the N-in-NX format. Then, they were asked to assess their risk of having a child with Down syndrome. RESULTS: Results showed a systematic higher risk assessment when pregnant women were presented with the 1-in-X format (mean = 3.57, standard deviation = 1.4) than with the N-in-NX format (mean = 3.03, standard deviation = 1.4), P = 0.007. Whereas the effect was shown to be not moderated by a differential comprehension of the two numerical formats, women with a low educational level and those who were at their first pregnancy were shown to be significantly more vulnerable. CONCLUSION: The present findings corroborate the existence of the 1-in-X effect in a real-world setting, showing that, in pregnant women, the 1-in-X format actually elicits a higher perceived risk of Down syndrome, compared with the N-in-NX format.

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inflammation; pneumonia; citokine

Background: We tested the hypothesis that acetyl-Lcarnitine (ALC) may have a protective and a curative role in chemotherapy-induced hyperalgesia in vivo, in animal models of cisplatin-, paclitaxel- and vincristine-induced neuropathy. In addition, the possible interaction between ALC and vincristine antineoplastic action was assessed. Materials and Methods: Chemotherapy-induced peripheral neuropathy (CIPN) was induced in different groups of rats. The effect of ALC was evaluated both when its administration was started together with the administration of anticancer drugs ("preventive" protocol) and when ALC administration was started later on during treatment ("curative" protocol). Results: The ALC treatment significantly prevented the lowering of the mechanical nociceptive threshold when the administration started concomitantly and, respectively, with cisplatin, paclitaxel and vincristine as compared to each drug alone. Furthermore, when ALC administration was started later on during treatment, at well-established neuropathy, ALC was able to restore the mechanical nociceptive threshold within a few days. Finally, experiments indicated that ALC does not interfere with the antitumor effects of vincristine. Conclusion: Considering the absence of any satisfactory treatment currently available for CIPN in a clinical setting, these are important observations, opening up the possibility of using ALC to treat a wide range of patients who have undergone chemotherapy and developed sensory peripheral neuropathy.