Aliskiren inhibits prorenin-induced human aortic smooth muscle cell migration

Background: In the present study, we investigated the potential effect of aliskiren on smooth muscle cell (SMC) migration in response to prorenin. Methods: Cultured human SMCs were incubated with angiotensinogen (ANG) (1.5 10-7M) and increasing concentrations of aliskiren (10-610-5M). After 24 h, SMC migration was assessed by Boydens chamber chemotactic assay using prorenin as chemotactic factor (10-8M). The effect of aliskiren on RhoA and Rac activity was also determined by G-LISA assay and the lamellipodia formation by rhodaminephalloidin staining. Changes in cell morphology were recorded in real-time using the iCelligence system. Results: Aliskiren determined, at 10-5M, a significant inhibition of SMC migration induced by prorenin (-66.418.1%; p > 0.05), while no significant effect was observed when PDGF-BB was utilized as chemotactic agent. Aliskiren also reduced Rac-GTP levels in response to prorenin (-54.2\ub15.4%) without affecting the RhoA-GTP levels. Finally, aliskiren inhibited both the lamellipodia formation and morphological changes induced by prorenin with no significant effect on PDGF-BB activity. Conclusions: Taken together, we provide the first evidence of the inhibitory action of aliskiren on SMC migration induced by prorenin

Modulation of the intrinsic neuronal excitability by multifunctional liposomes tailored for the treatment of alzheimer’s disease

Purpose: Nanotechnologies turned out to be promising in the development of diagnostic and therapeutic approaches toward neurodegenerative disorders. However, only a very scant number of nanodevices until now proved to be effective on preclinical animal models. Although specific tests in vivo are available to assess the potential toxicity of these nanodevices on cognitive functions, those to evaluate their biosafety in vitro on neurons are still to be improved. Materials and methods: We utilized the patch-clamp technique on primary cultures of cortical neural cells isolated from neonatal rats, aiming to evaluate their electrical properties after the incubation with liposomes (mApoE-PA-LIPs), previously proved able to cross the blood\u2013brain barrier and to be effective on mouse models of Alzheimer\u2019s disease (AD), both in the absence and in the presence of \u3b2-amyloid peptide oligomers. Results: Data show a high degree of biocompatibility, evaluated by lactate dehydrogenase (LDH) release and MTT assay, and the lack of cellular internalization. After the incubation with mApoE-PA-LIPs, neuronal membranes show an increase in the input resistance (from 724.14\ub176 M\u3a9 in untreated population to 886.06\ub186 M\u3a9 in the treated one), a reduction in the rheobase current (from 29.6\ub13 to 24.2\ub13 pA in untreated and treated, respectively), and an increase of the firing frequency, consistent with an ultimate increase in intrinsic excitability. Data obtained after co-incubation of mApoE-PA-LIPs with \u3b2-amyloid peptide oligomers suggest a retention of liposome efficacy. Conclusion: These data suggest the ability of liposomes to modulate neuronal electrical properties and are compatible with the previously demonstrated amelioration of cognitive functions induced by treatment of AD mice with liposomes. We conclude that this electrophysiological approach could represent a useful tool for nanomedicine to evaluate the effect of nanoparticles on intrinsic neuronal excitability

Il teatro ritrovato. Il santuario di Monte S. Nicola a Pietravairano (CE): la campagna di scavo dell’anno 2012

Campagna di scavo 2012 sul sito di Pietravairan