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Papers by Alessandro Addis

Cancer Research, 2013

Background: CRM1 (XPO1) is the exclusive exportin mediating transport of most tumor suppressor pr... more Background: CRM1 (XPO1) is the exclusive exportin mediating transport of most tumor suppressor proteins (TSPs) including p53, pRb, FOXO, APC and p21 out of the nucleus, abrogating their function. Methods: We tested the effects of the potent, selective, clinical stage oral SINE compound KPT-330 in prostate cancer (PrCa) models. Male SCID mice orthotopically (intraprostatic) inoculated with the DU145 PrCa, known to produce highly metastatic tumors with visceral metastases. In parallel, male CD1-nu/nu mice were inoculated with intracardiac and intratibial injections of the aggressive/bone-derived PrCa PC3, known to produce prominent osteolytic bone lesions. The effects of SINEs KPT-330 and KPT-251 on metastatic spreading were determined. Results: We previously demonstrated that SINE CRM1 antagonists KPT330 and KPT251 have potent antitumor effects on PrCa both in vitro and in vivo. Here, we demonstrate that KPT-330 reduces intraprostatic DU145 tumor burden as well as the incidence of ma...

EP Europace, 2018

Methods and results: Seventy-nine patients (33% female, mean age 63612 years, mean LA-diameter 45... more Methods and results: Seventy-nine patients (33% female, mean age 63612 years, mean LA-diameter 456x7mm) with persistent AF underwent CB2-based PVI in three german EP centers. After successful PVI a bonus freeze was applied in 18/79 (23%) patients. In 22/79 (28%) patients a no-bonus freeze protocol was applied. In 39 (49%) patients a time-to-effect protocol was utilized. A total of 313 pulmonary veins (PV) were identified and 313/313 (100%) PVs were successfully isolated. A transient phrenic nerve palsy occurred in 1/79 (1.3%) patients. One patient (1.3%) suffered from a postprocedural pericardial effusion, not requiring pericardial drainage. No further major complications occurred in this cohort. Follow-up was based on outpatient clinic visits at 3, 6 and 12 months including Holter-ECGs and telephonic interviews. Recurrence was defined as a symptomatic and/or documented atrial arrhythmia episode >30 sec excluding a 3-month blanking period. Follow-up was available for 79/79 (100%) patients with a median follow-up duration of 15 months (interquartile range 12-32). A total of 44/79 (55.7%) patients remained in stable sinus rhythm. The time to recurrence was 12 months (interquartile range 6.5-17). Of 22/44 (50%) patients with arrhythmia recurrence, a second procedure using radiofrequency ablation was conducted. After a mean of 1.3þ/-0.5 procedures a total of 59/79 (74.7%) patients remained in stable sinus rhythm. Conclusions: The use of the CB2 for PVI in patients suffering from persistent AF results in a single procedural success rate of 55.7% and a multiple procedural success rate of 74.7% after a median follow-up duration of 15 months.

Polymer foams are among the most studied scaffold for tissue engineering. Among them, cross-linke... more Polymer foams are among the most studied scaffold for tissue engineering. Among them, cross-linked polyurethane foams (PUFs) with slow degradation rate can be used as scaffolds for soft tissue engineering or as matrices of porous composites containing inorganic salts for hard tissue engineering. The foaming process has been set up using polymeric MDI, 2% water as expanding agent and Fe-acetyl acetonate as catalyst. On the whole, two families of foams (EC and EF) were developed using two different polyether-polyol formulations, the EF-type being more hydrophilic and more flexible than the EC-one. In vitro cytocompatibility tests with different cell lines demonstrated the ability of these matrices to stimulate cell adhesion and proliferation. In this work we investigated the in vivo behaviour of both EC and EF PU foams in the rat animal model to evaluate the extent of inflammatory reaction and the biodegradation rate. Discs of the EC- and EF-type foams were implanted in the dorsal subcutaneous tissue of male rats up to 42 weeks, explanted and histologically inspected together with the surrounding tissues by haematoxylin and eosin staining. The obtained results indicated a good biocompatibility of both foam types, the evoked inflammatory response being physiological. In particular, for the EF-based foams, at the material/tissue interface neovascularization and formation of new peripheral nerves were noticed. Moreover, the EF PUFs seem to promote the formation of mesenchimal tissue that, under particular stimuli, could promote the regeneration of the intended tissue

El objetivo de este estudio histologico era evaluar la osteointegracion de los implantes de titan... more El objetivo de este estudio histologico era evaluar la osteointegracion de los implantes de titanio cuyas superficies fueron tratadas con diferentes metodos en cerdos enanos.Se evaluaron seis superficies diferentes: SLA-Ti5 (aleacion de titanio, arenado utilizando oxido de aluminio y grabado utilizando acido nitrico y fluoridico); SLA-Ti4 (titanio comercialmente puro (CP)-Ti, arenado utilizando particulas grandes de arenilla de oxido de aluminio ademas de grabado acido con acido clorhidrico/sulfurico); HA (CP-Ti, arenado utilizando hidroxiapatita ademas de grabado con acido nitrico); DAE (aleacion de titanio, doble acido grabador utilizando acido fluorhidrico ademas de acido clorhidrico y sulfurico); ASD-Ti5 (aleacion de titanio, sedimentacion anodica provocada); ASD-Ti4 (CP-Ti, sedimentacion anodica provocada). Se utilizo un escaner microscopico electronico para evaluar la superficie microtopografica. Se detecto la composicion de los elementos de la superficie mediante EDS (espectr...

Journal of the Pancreas, 2007

Neurocritical Care, 2016

Background Therapeutic hypothermia (i.e., temperature management) is an effective option for impr... more Background Therapeutic hypothermia (i.e., temperature management) is an effective option for improving survival and neurological outcome after cardiac arrest and is potentially useful for the care of the critically ill neurological patient. We analyzed the feasibility of a device to control the temperature of the brain by controlling the temperature of the blood flowing through the neck. Methods A lumped parameter dynamic model, with onedimensional heat transfer, was used to predict cooling effects and to test experimental hypotheses. The cooling system consisted of a flexible collar and was tested on 4 adult sheep, in which brain and body temperatures were invasively monitored for the duration of the experiment. Results Model-based simulations predicted a lowering of the temperature of the brain and the body following the onset of cooling, with a rate of 0.4°C/h for the brain and 0.2°C/h for the body. The experimental findings showed comparable cooling rates in the two body compartments, with temperature reductions of 0.6 (0.2)°C/h for the brain and 0.6 (0.2)°C/h for the body. For a 70 kg adult human subject, we predict a temperature reduction of 0.64°C/h for the brain and 0.43°C/h for the body. Conclusions This work demonstrates the feasibility of using a non-invasive method to induce brain hypothermia using a portable collar. This device demonstrated an optimal safety profile and represents a potentially useful method for the administration of mild hypothermia and temperature control (i.e., treatment of hyperpyrexia) in cardiac arrest and critically ill neurologic patients.

Silk fibroin (SF) is the inner component of the silk fiber spun by Bombyx mori silkworm. It is co... more Silk fibroin (SF) is the inner component of the silk fiber spun by Bombyx mori silkworm. It is considered a valuable material for biotechnology and biomedical applications due to its unique properties including biocompatibility, oxygen and water vapor permeability, biodegradability, and minimal inflammatory reaction. Sericin, which constitutes the outer layer of the fiber, was recently studied by several authors who underlined its antioxidant, antibacterial and anti-inflammatory properties, its protective action for serum deprived cells, being moreover considered a triggering molecule for apatite deposition. Fibroin and sericin can be processed to obtain powders, films, gels, filaments, etc., so making different materials that can tailored to the requirements of the specific application. These processes induce structural transitions and morphological changes that have a great influence on the physical and biological properties of the resulting materials. In this work two different SF-based hydrogels (100% SF and 90/10SF-Ser) and a pure fibroin sponge were compared in an in vivo critical size defect study in order to evaluate their bone regeneration capability

Rivista della Stazione …, 2006

Résumé/Abstract This study is a first step to evaluate the properties of the new bioactive glass ... more Résumé/Abstract This study is a first step to evaluate the properties of the new bioactive glass Crystal Bio Tech both as a bulk and a macroporous material. Both types of glass have been used to repair a 10 mm defect in six rabbit limbs and the implants have been ...

International Journal of Stem cell Research & Therapy, 2017

Regeneration of atrophied alveolar bone prior to insertion of dental implants is a major challeng... more Regeneration of atrophied alveolar bone prior to insertion of dental implants is a major challenge for oral and maxillofacial surgery. It has been reported that Bone Marrow (BM) derived Mesenchymal Stromal Cells (MSC) retain therapeutic potential for bone regeneration.

EuroIntervention, 2016

Interventional closure of post-myocardial infarction ventricular septal defects (VSD) is an alter... more Interventional closure of post-myocardial infarction ventricular septal defects (VSD) is an alternative treatment option to surgical repair. However, only limited evidence exists concerning the interventional closure of a VSD. This review seeks to establish an overview of the existing literature and to carry out a systematic analysis of the success rate and clinical outcome of this procedure. Methods and results: We conducted a comprehensive systematic literature search to evaluate the existing evidence of percutaneous device closure of post-infarction VSD. Patient series with fewer than five reported cases were excluded. In total, 13 series were identified, with an overall inclusion of 273 patients. Mean patient age was 70 years. Cardiogenic shock was present in 48% of cases at the time of intervention. Device closure within the first 14 days (acute phase) after VSD detection was performed in 42% of cases. Technical success rate was high (>75%). Successful device implantation rate was 89%. Overall inhospital/30-day mortality was 32%. Major complications included device embolisation, ventricular perforation and arrhythmias. Conclusions: Percutaneous device closure of post-myocardial infarction VSD is a valuable alternative to surgical repair, with the advantage of immediate shunt reduction to prevent haemodynamic deterioration. A high rate of technically successful percutaneous procedures can be achieved; however, the mortality rate remains high, especially in cardiogenic shock patients.

The evaluation of both qualitative and quantitative osteointegration is essential to determine bo... more The evaluation of both qualitative and quantitative osteointegration is essential to determine bone scaffolds ability to repair defects and its real biofunctionality. Bone densitometry is considered as a good tool for noninvasively monitoring of healing process. In literature, there are few works about bone density differences between human and most employed animal models, and also on differences between animals with various skeletal development. The aim of this study was to collect normal bone mineral density (BMD) values about tibia in different animal models, because tibia was regarded as the most common experimental implant site

Journal of Cardiovascular Electrophysiology, 2022

El objetivo de este estudio fue evaluar las fases tempranas de consolidacion osea alrededor de do... more El objetivo de este estudio fue evaluar las fases tempranas de consolidacion osea alrededor de dos superficies de implantes diferentes. Para ello se utilizaron 4 cerdos minipig. Los implantes con una superficie rugosa de titanio (IT! arenado/grabado al acido y Branemark TiUnite) se colocaron en los maxilares de los animales y se programo su sacrificio para obtener tiempos de consolidacion de 3 dias y de 1, 2, 3, 4, 5, 6 y 7 semanas. El analisis histologico revelo un patron similar en las fases de consolidacion osea alrededor de ambos tipos de implantes entre los 3 dias y las 7 semanas. Este patron consistio en la sustitucion del coagulo sanguineo y las particulas oseas por un tejido conjuntivo provisional durante las primeras semanas y posteriormente por tejido mineralizado y espacios medulares. Ambas superficies rugosas permitieron que se produjera la «osteo genesis por contacto».