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Montagna M.,Laboratory of Clinical Pharmacokinetics | Montillo M.,Niguarda Hospital | Avanzini M.A.,Pediatric Hematology Oncology Unit | Tinelli C.,Clinical Epidemiology and Biometric Unit | And 7 more authors.
Haematologica | Year: 2011

Alemtuzumab serum levels and clinical response after subcutaneous administration (10 mg 3 times/week for six weeks) have been explored in 29 chronic lymphocytic leukemia patients receiving the monoclonal antibody as consolidation. Serum concentrations after each administration gradually increased during the first week and more markedly during weeks 2 and 3, approaching the steady-state at week 6. Absorption continued slowly through the tissues for about 2- 3 weeks after the last administration, starting to decrease thereafter. Difference between Responders and Non-responders was statistically significant: maximal concentration (Cmax) was 1.69 μg/mL vs. 0.44 μg/mL; concentration before subcutaneous administration (Cpre-dose) on day 15 was 0.7 vs. 0.21 μg/mL, area under curve (AUC0-12h) was 11.09 vs. 2.26 μg x h/mL for Responders and Non-responders, respectively. Higher systemic exposure to alemtuzumab correlated with a better clinical response and minimal residual disease. Results suggest that an adjusted schedule according to serum level could improve clinical outcome of patients receiving subcutaneous alemtuzumab. © 2011 Ferrata Storti Foundation.

Bozzini S.,Polytechnic of Milan | Bozzini S.,ETH Zurich | Petrini P.,Polytechnic of Milan | Tanzi M.C.,Polytechnic of Milan | And 5 more authors.
International Journal of Artificial Organs | Year: 2011

Purpose: Presently there is interest today in designing improved titanium surfaces capable of high bioactivity in order to promote strong anchorage of the bone surrounding implants while at the same time discouraging bioadhesion. Poly(ethylene glycol)-modified (PEG) alkane phosphate and OH-terminated alkane phosphates have been demonstrated to be spontaneously adsorbed onto titanium oxide surfaces and produce surfaces with different protein resistance in relation to the PEG surface density. This study aims to evaluate caries-associated Streptococcus mutans (S. mutans) adhesion and osteoblast proliferation while varying the PEG surface density of titanium surfaces. Methods: Bacterial adhesion was quantified by fluorescence microscopy and SAOS-2 human osteoblast proliferation was evaluated up to 7 days of culture in vitro. Metabolic activity of osteoblasts was measured by MTT test and the secretion of extracellular matrix proteins (osteopontin, osteocalcin and type I collagen) in culture medium was determined by immunoenzymatic assays. Results: As the PEG surface density increased, the bacterial adhesion considerably decreased when compared to uncoated titanium surfaces. The monomolecular coatings proved to be capable of supporting osteoblast proliferation with the greatest levels of metabolic activity at the highest PEG surface concentrations. Conclusions: These results are extremely promising for potential clinical application in implant uses where both reduction of bacteria adhesion and stimulation of bone formation are highly desirable. © 2011 Wichtig Editore.

Pre D.,University of Pavia | Ceccarelli G.,University of Pavia | Gastaldi G.,University of Pavia | Asti A.,University of Pavia | And 6 more authors.
Bone | Year: 2011

Several studies have demonstrated that tissue culture conditions influence the differentiation of human adipose-derived stem cells (hASCs). Recently, studies performed on SAOS-2 and bone marrow stromal cells (BMSCs) have shown the effectiveness of high frequency vibration treatment on cell differentiation to osteoblasts. The aim of this study was to evaluate the effects of low amplitude, high frequency vibrations on the differentiation of hASCs toward bone tissue. In view of this goal, hASCs were cultured in proliferative or osteogenic media and stimulated daily at 30. Hz for 45. min for 28. days. The state of calcification of the extracellular matrix was determined using the alizarin assay, while the expression of extracellular matrix and associated mRNA was determined by ELISA assays and quantitative RT-PCR (qRT-PCR). The results showed the osteogenic effect of high frequency vibration treatment in the early stages of hASC differentiation (after 14 and 21. days). On the contrary, no additional significant differences were observed after 28. days cell culture. Transmission Electron Microscopy (TEM) images performed on 21. day samples showed evidence of structured collagen fibers in the treated samples.All together, these results demonstrate the effectiveness of high frequency vibration treatment on hASC differentiation toward osteoblasts. © 2011 Elsevier Inc.

Giordano C.,Polytechnic of Milan | Saino E.,University of Pavia | Rimondini L.,University of Piemonte Orientale | Pedeferri M.P.,Polytechnic of Milan | And 4 more authors.
Colloids and Surfaces B: Biointerfaces | Year: 2011

Bacterial contamination of implanted devices is a common cause of their failure. The aim of the present study was to assess the capability of electrochemical procedures to: (a) promote the formation of anatase on the surface of commercially pure Grade 2 Ti and Ti Grade 5 (Ti6Al4V) alloy; (b) inhibit in vitro biofilm formation of Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus mutans and Porphyromonas gingivalis and oral plaque in vivo, (c) preserve favorable response of osteoblasts and fibroblasts to materials surfaces. Ti Grade 2 and Ti Grade 5 were respectively anodized at two different voltages: 90 and 130 V for pure titanium; 100 and 120 V for Ti6Al4V alloy. Surface characterization was performed by scanning electron microscopy (SEM) equipped with EDS probe, laser profilometry and X-ray diffractometry. Bacterial adhesion characterization was performed either in vitro and in vivo in patients. Osteoblast and fibroblast response was evaluated by metabolic activity assessment. The higher voltage applied in the anodization treatment of pure titanium (130 V) and Ti6Al4V alloy (120 V) surfaces, compared to the untreated pure titanium and Ti6Al4V and to lower voltage treatments, resulted in a greater decrease in bacterial attachment and biofilm formation in both in vitro and in vivo experiments. In contrast, the high voltage treatments were found to promote osteoblasts and fibroblasts proliferation. The observations indicated that the experimented high voltage anodization treatments may contribute to preserve the tissue integration and reduce bacteria colonization of titanium and titanium alloy for implantable applications. © 2011 Elsevier B.V.

Fortunati E.,University of Perugia | Armentano I.,University of Perugia | Iannoni A.,University of Perugia | Barbale M.,Novamont S.p.A | And 6 more authors.
Journal of Applied Polymer Science | Year: 2012

The aim of this work was to study the effect of the innovative combination of microcrystalline cellulose (MCC) and silver nanoparticles (Ag) on the poly (lactide acid) (PLA) composite properties, to modulate the PLA mechanical response and induce an antibacterial effect. The preparation and characterization of PLA-based composites with MCC and Ag nanoparticles by twin-screw extrusion followed by injection molding is reported. A film procedure was also performed to obtain PLA and PLA composite films with a thickness ranged between 20 and 60 Î. The analysis of disintegrability in composting conditions by means of visual, morphological, thermal, and chemical investigations was done to gain insights into the post-use degradation processes. Tensile test demonstrated the MCC reinforcing effect, while a bactericidal activity of silver-based composites against a Gram-negative bacteria (Escherichia coli) and a Gram-positive bacteria (Staphylococcus aureus) was detected at any time points and temperatures analyzed. Moreover, the disintegrability in composting showed that MCC is able to promote the degradation process. The combination of MCC and Ag nanoparticles in PLA polymer matrix offers promising perspectives to realize multifunctional ternary composites with good mechanical response and antibacterial effect, maintaining the optical transparency and the disintegrability, hence suitable for packaging applications. © 2011 Wiley Periodicals, Inc.

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