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Only 50% of hypertensive patients receive an appropriate treatment to normalize blood pressure (BP). Although monotherapy is often adequate in normalizing BP, it is sometimes necessary to start with combination therapy. The aim of the study was to evaluate the efficacy of nebivolol alone and in association with hydrochlorothiazide (HCT) in reducing BP in hypertensive patients with new-onset, mild-to-moderate hypertension, and to assess the effect of combination therapy on glucose and lipid metabolism. At enrollment, patients underwent a full cardiovascular and metabolic evaluation. Patients were then prescribed nebivolol (5 mg/day). After 1 month, in those patients whose BP was not normalized, HCT 12.5 mg was added and increased further to 25 mg after 1 month in those whose BP still was not normalized. All patients were assessed at monthly intervals for a further 5 months. We enrolled 233 treatment-naive patients. After the first month of treatment with nebivolol, 70% of patients had normalized BP. The addition of HCT increased responder rates to 94%. An improvement in glucose metabolism was noted with nebivolol alone (at 1 month, the reduction in Homeostasis Model Assessment of Insulin Resistance [HOMA-IR] was 26% and remained stable at 6 months); the adjunct of HCT blunted the reduction in HOMA-IR. No significant changes on lipid profile were noted with nebivolol, either alone or in combination therapy. Nebivolol is effective in mild-to-moderate hypertension and associated with favorable metabolic effects. The addition of HCT optimizes BP control in a high number of patients resistant to monotherapy without a negative impact on patients' glucose and lipid profile.


Cardinale A.,IRCCS San Raffaele Pisana | Biocca S.,University of Rome Tor Vergata
International Journal of Cell Biology | Year: 2013

Prion diseases or transmissible spongiform encephalopathies (TSE) are a group of neurodegenerative and infectious disorders characterized by the conversion of a normal cellular protein PrPC into a pathological abnormally folded form, termed PrPSc. There are neither available therapies nor diagnostic tools for an early identification of individuals affected by these diseases. New gene-based antibody strategies are emerging as valuable therapeutic tools. Among these, intrabodies are chimeric molecules composed by recombinant antibody fragments fused to intracellular trafficking sequences, aimed at inhibiting, in vivo, the function of specific therapeutic targets. The advantage of intrabodies is that they can be selected against a precise epitope of target proteins, including protein-protein interaction sites and cytotoxic conformers (i.e., oligomeric and fibrillar assemblies). Herein, we address and discuss in vitro and in vivo applications of intrabodies in prion diseases, focussing on their therapeutic potential. © 2013 Alessio Cardinale and Silvia Biocca.


Shewan L.G.,Monash University | Shewan L.G.,University of Warwick | Rosano G.,IRCCS San Raffaele Pisana | Henein M.,Umea University | And 2 more authors.
International Journal of Cardiology | Year: 2014

All authors of manuscripts in the International Journal of Cardiology family of journals: The International Journal of Cardiology, IJC Heart & Vessels and IJC Metabolic & Endocrine are required to make a binding statement that they as authors adhere to the following principles:That the corresponding author has the approval of all other listed authors for the submission and publication of all versions of the manuscript, that all authors have made a significant independent contribution and that no one who justifies being an author has been omitted from authorshipThat the work has not been published nor is under consideration for publication elsewhere other than in oral, poster or abstract format, and that appropriate attribution and citation is given for any material reproduced from any other source including the authors' prior publicationsThat the material in the manuscript has been acquired according to modern ethical standards and has been approved by the legally appropriate ethical committee(s)That all material conflicts of interest have been declared including the use of paid medical writers and their funding source.That the manuscript will be maintained on the servers of the journals and held to be a valid publication by the journals only as long as all statements in these principles remain true, and that the authors have a duty to notify the journal editors immediately if any of the statements above ceases to be true withdrawn. © 2013 Elsevier Ireland Ltd.


Sale P.,IRCCS San Raffaele Pisana | Franceschini M.,IRCCS San Raffaele Pisana
European Journal of Physical and Rehabilitation Medicine | Year: 2012

Mirror neurons are a specific class of neurons that are activated and discharge both during observation of the same or similar motor act performed by another individual and during the execution of a motor act. Different studies based on non invasive neuroelectrophysiological assessment or functional brain imaging techniques have demonstrated the presence of the mirror neuron and their mechanism in humans. Various authors have demonstrated that in the human these networks are activated when individuals learn motor actions via execution (as in traditional motor learning), imitation, observation (as in observational learning) and motor imagery. Activation of these brain areas (inferior parietal lobe and the ventral premotor cortex, as well as the caudal part of the inferior frontal gyrus [IFG]) following observation or motor imagery may thereby facilitate subsequent movement execution by directly matching the observed or imagined action to the internal simulation of that action. It is therefore believed that this multi-sensory actionobservation system enables individuals to (re) learn impaired motor functions through the activation of these internal action-related representations. In humans, the mirror mechanism is also located in various brain segment: in Broca's area, which is involved in language processing and speech production and not only in centres that mediate voluntary movement, but also in cortical areas that mediate visceromotor emotion-related behaviours. On basis of this finding, during the last 10 years various studies were carry out regarding the clinical use of action observation for motor rehabilitation of sub-acute and chronic stroke patients.


Stocchi F.,IRCCS San Raffaele Pisana | Olanow C.W.,IRCCS San Raffaele Pisana | Olanow C.W.,Mount Sinai School of Medicine
Movement Disorders | Year: 2013

A neuroprotective or disease-modifying therapy that can slow or stop disease progression and prevent the development of intolerable disability is the major unmet medical need in the treatment of Parkinson's disease (PD). Many putative neuroprotective agents have been identified in the laboratory, but none has been unequivocally demonstrated to provide disease-modifying effects in PD patients, even when clinical trials are positive. Obstacles to defining a neuroprotective therapy in PD include: (1) uncertainty about the cause of PD and precisely what to target, (2) a reliable animal model in which to test putative neuroprotective agents that accurately predicts results in PD patients, (3) insight about which dose to employ in clinical trials and which patient group to study, (4) a clinical trial design that reliably differentiates disease-modifying and symptomatic effects and that is acceptable to regulatory authorities, and (5) the cost and time of the development program. Advances have been made in each of these areas, thereby increasing the prospects of developing a neuroprotective or disease-modifying therapy in the not-too-distant future. These issues are reviewed in the present article. © 2013 Movement Disorder Society.

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