Milena Fini

Publications of Milena Fini

• Two hits are better than one: targeting both phosphatidylinositol 3-kinase and mammalian target of rapamycin as a therapeutic strategy for acute leukemia treatment.

  Authors: Alberto M Martelli, Francesca Chiarini, Camilla Evangelisti, Alessandra Cappellini, Francesca Buontempo, Daniela Bressanin, Milena Fini, James A McCubrey

  Oncotarget. 05/2012;

  Phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) are two key components of the PI3K/Akt/mTOR signaling pathway. This signal transduction cascade regulates a wide range ofPhosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) are two key components of the PI3K/Akt/mTOR signaling pathway. This signal transduction cascade regulates a wide range of physiological cell processes, that include differentiation, proliferation, apoptosis, autophagy, metabolism, motility, and exocytosis. However, constitutively active PI3K/Akt/mTOR signaling characterizes many types of tumors where it negatively influences response to therapeutic treatments. Hence, targeting PI3K/Akt/mTOR signaling with small molecule inhibitors may improve cancer patient outcome. The PI3K/Akt/mTOR signaling cascade is overactive in acute leukemias, where it correlates with enhanced drug-resistance and poor prognosis. The catalytic sites of PI3K and mTOR share a high degree of sequence homology. This feature has allowed the synthesis of ATP-competitive compounds targeting the catalytic site of both kinases. In preclinical models, dual PI3K/mTOR inhibitors displayed a much stronger cytotoxicity against acute leukemia cells than either PI3K inhibitors or allosteric mTOR inhibitors, such as rapamycin. At variance with rapamycin, dual PI3K/mTOR inhibitors targeted both mTOR complex 1 and mTOR complex 2, and inhibited the rapamycin-resistant phosphorylation of eukaryotic initiation factor 4E-binding protein 1, resulting in a marked inhibition of oncogenic protein translation. Therefore, they strongly reduced cell proliferation and induced an important apoptotic response. Here, we reviewed the evidence documenting that dual PI3K/mTOR inhibitors may represent a promising option for future targeted therapies of acute leukemia patients.

• Preliminary 2-Year Report on Treatment Outcomes for 6-mm-Long Implants in Posterior Atrophic Mandibles.

  Authors: Francesco Pieri, Nicolo Nicoli Aldini, Milena Fini, Claudio Marchetti, Giuseppe Corinaldesi

  The International journal of prosthodontics. 05/2012; 25(3):279-89.

  Purpose: The aim of this study was to prospectively evaluate clinical and radiographic outcomes of ultrashort implants (4-mm diameter, 6-mm length) supporting fixed partial dentures in severelyPurpose: The aim of this study was to prospectively evaluate clinical and radiographic outcomes of ultrashort implants (4-mm diameter, 6-mm length) supporting fixed partial dentures in severely atrophic posterior mandibles. Materials and Methods: Twenty-five patients with posterior edentulous mandibular spans and 7- to 8-mm residual bone heights above the mandibular canal were enrolled. In total, 61 submerged implants were placed and loaded 5 to 6 months later. Patients were followed for 2 years after prosthesis connection with clinical, radiographic, and resonance frequency analysis (RFA) examinations. Results: Two implants failed in one patient before loading; all other implants showed favorable clinical and radiographic findings throughout the observation period (2-year survival and success rate: 96.8%). Postoperative pain and swelling were negligible. Mean changes in marginal bone levels were stable (0.40 ± 0.23, 0.51 ± 0.38, and 0.60 ± 0.13 mm after 6 months and 1 and 2 years, respectively) and were unaffected by measured crown-to-implant ratios (range: 1.31 to 3.12). Mean RFA values increased significantly from implant placement (67.35 ± 6.67) to 2 years (72.91 ± 5.07, P < .0001). Prosthetic complications included two prosthesis decementations, three ceramic veneer chippings, and one prosthesis screw loosening. Conclusion: Within the limitations of the short follow-up period, the use of 6-mm-long implants was a predictable treatment method for patients with atrophic posterior mandibles and increased crown-to-implant ratios.

• TISSUE ENGINEERING FOR TOTAL MENISCAL SUBSTITUTION. Animal study in sheep model: results at 12 months.

  Authors: Elizaveta Kon, Giuseppe Filardo, Matilde Tschon, Milena Fini, Gianluca Giavaresi, Leonardo Marchesini Reggiani, Catharina Chiari, Stefan Nehrer, Ivan Martin, Donald Salter, Luigi Ambrosio, Maurilio Marcacci

  Tissue engineering. Part A. 04/2012;

  The aim of the study was to investigate the use of a hyaluronic acid/polycaprolactone material for meniscal tissue engineering and to evaluate the tissue regeneration after the augmentation of theThe aim of the study was to investigate the use of a hyaluronic acid/polycaprolactone material for meniscal tissue engineering and to evaluate the tissue regeneration after the augmentation of the implant with expanded autologous chondrocytes. Eighteen skeletally mature sheep were treated. The animals were divided in three groups: cell-free scaffold, scaffold seeded with autologous chondrocytes and meniscectomy alone. The implant was sutured to the capsule and to the meniscal ligament. At 12 months gross assessment, histology and histomorphometry were used to assess meniscus implant, knee joint and osteoarthritis development. All implants showed excellent capsular ingrowth at the periphery. Implant gross assessment showed significant differences between cell-seeded and cell-free groups (p=0.011). The histological analysis indicated a cellular colonization throughout the implanted constructs. Avascular cartilaginous tissue formation was significantly more frequent in the cell-seeded constructs. Joint gross assessment showed that sheep treated with scaffold implantation achieved a significant higher score than those who underwent meniscectomy (p<0.0005), and OARSI score showed that osteoarthritic changes were significantly less in the cell-seeded group than in meniscectomy group (p=0.047), even though results were not significantly superior to those of the cell-free scaffold. Seeding of the scaffold with autologous chondrocytes increases its tissue regeneration capacity, providing a better fibrocartilaginous tissue formation. The study suggests the potential of the novel hyaluronic acid/polycaprolactone scaffold for total meniscal substitution, although this approach has to be further improved before being applied into clinical practice.

• EARLY TERM EFFECT OF ADULT CHONDROCYTE TRANSPLANTATION IN AN OSTEOARTHRITIS ANIMAL MODEL.

  Authors: Giovanna Desando, Carola Cavallo, Matilde Tschon, Gianluca Giavaresi, Lucia Martini, Milena Fini, Roberto Giardino, Andrea Facchini, Brunella Grigolo

  Tissue engineering. Part A. 03/2012;

  Abstract In this study, we investigated the efficacy of the transplantation of autologous articular chondrocytes seeded onto a hyaluronan based scaffold, known as Hyaff®-11, on the treatment of earlyAbstract In this study, we investigated the efficacy of the transplantation of autologous articular chondrocytes seeded onto a hyaluronan based scaffold, known as Hyaff®-11, on the treatment of early cartilage lesions in a rabbit osteoarthritis (OA) model. The hypothesis of the study was that this treatment could enhance cartilage repair after OA induction. OA was induced surgically by Anterior Cruciate Ligament Transection (ACLT) in thirty rabbits. Animals were divided in three groups, according to treatment: group 1:ACLT; group 2: Chondrocytes+Hyaff®-11; group 3: Hyaff®-11 alone. Animals were euthanized respectively at 3 and 6 months after the treatment. Histomorphometrical analyses were performed by means of FI, CT and SBT evaluations. Histological appearance was scored according to Modified Kraus' Mankin and OARSI scores. Immunohistochemical analyses were carried out for type I and II collagens, MMP-1 and MMP-3. Comparison between groups and follow-up for each outcome was performed with general linear model with Sidak correction. Histomorphometrical evaluations at 3 and 6 months demonstrated that OA lesions significantly worse followed by Hyaff®-11 treatment, whereas Chondrocytes+ Hyaff®-11 treatment had the best overall subjective grade. Overall raw histological scores demonstrated a significant improvement with chondro-HA treatment at 3 months compared to HA in cartilage repair processes. Immunohistochemical analyses displayed a strong positivity for type II collagen in Chondrocytes+ Hyaff®-11group from 3 months compared to HA group. No staining was observed in MMP-3 expression in this group at any experimental point. The use of Chondrocytes+ Hyaff®-11 for the treatment of early OA lesions produced, already at 3 months, a repair tissue showing better macroscopic, histological and immunohistochemical results than those observed after Hyaff®-11 treatment. Thus, the transplantation of Chondrocytes+ Hyaff®-11 would seem to be advocated in the very early stage of the OA disease when a precocious action is mandatory.

• Rehabilitation of the Atrophic Posterior Maxilla Using Short Implants or Sinus Augmentation with Simultaneous Standard-Length Implant Placement: A 3-Year Randomized Clinical Trial.

  Authors: Francesco Pieri, Nicolò Nicoli Aldini, Milena Fini, Claudio Marchetti, Giuseppe Corinaldesi

  Clinical implant dentistry and related research. 03/2012;

  Purpose: To evaluate whether 6-mm-long implants (test group) could be a suitable alternative to standard-length implants (≥11 mm; control group) placed simultaneously with a sinus augmentation forPurpose: To evaluate whether 6-mm-long implants (test group) could be a suitable alternative to standard-length implants (≥11 mm; control group) placed simultaneously with a sinus augmentation for the treatment of atrophic posterior maxillae. Materials and Methods: In total, 68 patients having 6 to 7 mm of residual bone height and at least 6 mm thickness below the sinus were randomly allocated to the two treatment groups. Two or three implants were placed in each patient and submerged for 4 months. Outcome measures were implant failures, complications, operation time, postoperative pain and swelling, soft tissue parameters, marginal bone levels, and implant stability quotient (ISQ) values. Patients were followed for 3 years after loading. Results: Two dropouts occurred, one in each group. Three of 73 control implants and one of 71 test implants failed. At 3 years, mean marginal bone loss was 0.57 ± 0.82 mm in the control group versus 0.45 ± 0.34 mm in the test group. No significant difference was observed between groups in terms of implant failures, prosthetic complications, soft tissue parameters, marginal bone loss, or ISQ values. However, the control procedure required significantly longer operation times and led to more surgical complications, pain, and swelling, compared with the test procedure. Conclusions: Both techniques showed similar clinical and radiographic outcomes at 3 years, but the short implants provided advantages in terms of reduced surgical time and invasiveness.

• New PMMA-based composites for preparing spacer devices in prosthetic infections.

  Authors: Gianluca Giavaresi, Elisa Bertazzoni Minelli, Maria Sartori, Anna Benini, Annapaola Parrilli, Maria Cristina Maltarello, Francesca Salamanna, Paola Torricelli, Roberto Giardino, Milena Fini

  Journal of materials science. Materials in medicine. 02/2012;

  Even though the systemic antibiotic therapy is usually applied after prosthetic infections surgical treatments, it is unable to reach the infection site in sufficient concentrations to eradicateEven though the systemic antibiotic therapy is usually applied after prosthetic infections surgical treatments, it is unable to reach the infection site in sufficient concentrations to eradicate bacteria. Delivering antibiotics locally with the use of custom made device (spacer or nail coating) might eradicate or reduce the infection and the risk of recolonization, providing a very high concentration of antibiotic. PMMA-based (Mendec Spine(®)) composites with BaSO(4) were enriched with β-tricalcium phosphate (Porosectan-TCP) or only a slightly higher BaSO(4) concentration (Porosectan-BaSO(4)) to obtain higher porosity. The aim of the study was to evaluate: (i) drug absorption capability and drug release kinetics in vitro soaking them with a combined solution of gentamicin and vancomycin, (ii) their in vitro and in vivo biocompatibility, and finally, (iii) they were tested preliminarily in an experimental model of bone infection. The simultaneous presence of β-TCP and BaSO(4) resulted in the formation of a texture of interconnecting channels with different diameters, from a few microns to several hundred microns, which totally filled the material. The porosity, determined by microcomputed tomography, was significantly higher in both tested plain composites (Porosectan-TCP: +17.3%; Porosectan-BaSO(4): +7.5%) in comparison to control composite material (Mendec Spine(®)). The kinetics of antibiotic release from composites was rapid and complete, producing high drug concentrations for a short period of time. Both composites showed a good level of biocompatibility. The osteomyelitic model confirmed that both composites, soaked in antibiotic solution, were able to cure bone infection. These composites could be useful for preparing devices for prosthetic joint infections treatment also allowing the use of antibiotics solution at required concentrations.

• Conjugation of hydroxyapatite nanocrystals with human immunoglobulin G for nanomedical applications.

  Authors: Michele Iafisco, Elena Varoni, Michele Di Foggia, Stefano Pietronave, Milena Fini, Norberto Roveri, Lia Rimondini, Maria Prat

  Colloids and surfaces. B, Biointerfaces. 02/2012; 90:1-7.

  Inorganic nanosized drug carriers are a promising field in nanomedicine applied to cancer. Their conjugation with antibodies combines the properties of the nanoparticles themselves with the specificInorganic nanosized drug carriers are a promising field in nanomedicine applied to cancer. Their conjugation with antibodies combines the properties of the nanoparticles themselves with the specific and selective recognition ability of the antibodies to antigens. Biomimetic carbonate-hydroxyapatite (HA) nanoparticles were synthesized and fully characterized; human IgGs, used as model antibodies, were coupled to these nanocrystals. The maximum loading amount, the interaction modelling, the preferential orientation and the secondary structure modifications were evaluated using theoretical models (Langmuir, Freundlich and Langmuir-Freundlich) spectroscopic (UV-Vis, Raman), calorimetric (TGA), and immunochemical techniques (ELISA, Western Blot). HA nanoparticles of about 30 nm adsorbed human IgGs, in a dose-dependent, saturable and stable manner with micromolar affinity and adsorption capability around 2.3 mg/m(2). Adsorption isotherm could be described by Langmuir-Freundlich model, and was due to both energetically homogeneous and heterogeneous binding sites on HA surface, mainly of electrostatic nature. Binding did not induce secondary structure modification of IgGs. A preferential IgG end-on orientation with the involvement of IgG Fc moiety in the adsorption seems most probable due to the steric hindrance of their Fab domains. Biomimetic HA nanocrystals are suitable substrates to produce nanoparticles which can be functionalized with antibodies for efficient targeted drug delivery to tumours.

• The effect of zoledronate-hydroxyapatite nanocomposites on osteoclasts and osteoblast-like cells in vitro.

  Authors: Elisa Boanini, Paola Torricelli, Massimo Gazzano, Milena Fini, Adriana Bigi

  Biomaterials. 01/2012; 33(2):722-30.

  This study demonstrates that zoledronate containing hydroxyapatite nanocrystals (HA-ZOL) can be synthesized as a single crystalline phase up to a zoledronate content of about 7 wt% by directThis study demonstrates that zoledronate containing hydroxyapatite nanocrystals (HA-ZOL) can be synthesized as a single crystalline phase up to a zoledronate content of about 7 wt% by direct synthesis in aqueous solution, at variance with what previously found for alendronate-hydroxyapatite nanocrystals (HA-AL). On increasing zoledronate incorporation, the length of the coherent crystalline domains and the crystal dimensions of hydroxyapatite decrease, whereas the specific surface area increases. Full profile fitting of the powder X-ray diffraction patterns does not indicate major structural modifications, but an increase of the hydroxyapatite unit cell, on increasing zoledronate content. These data, together with a structural similarity between hydroxyapatite and calcium zoledronate, suggest a preferential interaction between zoledronate and the hydroxyapatite faces parallel to the c-axis direction. Osteoblast-like MG-63 cells and human osteoclasts were cultured on HA-ZOL nanocrystals and as a comparison on HA-AL nanocrystals containing almost the same (about 7 wt%) bisphosphonate amount. The beneficial influence of bisphosphonates on osteoblast proliferation and differentiation is enhanced when the tests are performed in co-cultures. Similarly, the reduction of osteoclast proliferation and the increase of Caspase 3 production are dramatically enhanced in co-cultures, which highlight an even greater influence of HA-ZOL than HA-AL on osteoclast apoptosis.

• Long-term Results following a Cranial Hydroxyapatite Prosthesis implantation in a large Skull Defect Model.

  Authors: Lucia Martini, Guido Staffa, Gianluca Giavaresi, Francesca Salamanna, Annapaola Parrilli, Elena Serchi, Daniele Pressato, Elena Arcangeli, Milena Fini

  Plastic and reconstructive surgery. 12/2011;

  BACKGROUND:: A large skull defect may occur after different events such as trauma, tumour resection, vascular injuries etc. There is still some doubt about the best material to use forBACKGROUND:: A large skull defect may occur after different events such as trauma, tumour resection, vascular injuries etc. There is still some doubt about the best material to use for reconstruction. Hydroxyapatite ceramic is one of the materials in use and its biocompatibility and osteoconductivity are well established. OBJECT:: This study evaluated the interaction of a commercial hydroxyapatite custom-made prosthesis implanted in a large skull defect, to assess its osteointegration and its habitability with new formed bone over time. METHODS:: Ten sheep underwent craniectomy and reconstruction of the skull defect with a porous hydroxyapatite cranial prosthesis. The animals were divided into two groups: Group A was sacrificed after 6 months and Group B after 12 months. At the end of the experimental times each implant was evaluated macroscopically, radiologically and analyzed by micro-CT, histology, histomorphometry and microhardness techniques. RESULTS:: During the study no adverse events occurred and there was no evidence of inflammation or negative tissue reactions. Histology and histomorphometry showed new bone formation inside the implant at both experimental times; newly formed bone had increased significantly (p <0.05) by over 300% between 6 and 12 months. 3D micro-CT analysis showed new bone formation and material remodeling. Microhardness analysis indicated that the mineralization process and the mechanical properties of newly formed bone were not altered. CONCLUSIONS:: The hydroxyapatite prosthesis showed its osteoconductivity and good biocompatibility. A low rate of fibrous tissue formation and a high rate of bony regeneration was found.

• Magnesium and strontium doped octacalcium phosphate thin films by matrix assisted pulsed laser evaporation.

  Authors: Elisa Boanini, Paola Torricelli, Milena Fini, Felix Sima, Natalia Serban, Ion N Mihailescu, Adriana Bigi

  Journal of inorganic biochemistry. 11/2011; 107(1):65-72.

  Octacalcium phosphate (OCP) is a promising alternative to hydroxyapatite as biomaterial for hard tissue repair. In this study we successfully applied Matrix Assisted Pulsed Laser Evaporation (MAPLE)Octacalcium phosphate (OCP) is a promising alternative to hydroxyapatite as biomaterial for hard tissue repair. In this study we successfully applied Matrix Assisted Pulsed Laser Evaporation (MAPLE) to deposit Mg and Sr doped OCP (MgOCP and SrOCP), as well as OCP, thin films on titanium substrates. OCP, Mg-substituted and Sr-substituted OCP were synthesized in aqueous medium, then were suspended in deionised water, frozen at liquid nitrogen temperature and used as targets for MAPLE experiments. The depositions were carried out using a KrF* excimer laser source (λ=248 nm, τ(FWHM)=25 ns) in mild conditions of temperature and pressure. The results of X-ray diffraction, infrared spectroscopy, scanning electron microscopy and energy dispersive spectroscopy investigations revealed that the OCP thin films are deposited in the form of cauliflower-like aggregates and droplets, as well as crystal fragments, with a homogeneous distribution of magnesium and strontium on the surface of the coatings. Human osteoblast-like MG-63 cells were cultured on the different biomaterials up to 14days. MgOCP and SrOCP coatings promote osteoblast proliferation and differentiation with respect to OCP. Under these experimental conditions, the production of procollagen-type I, transforming growth factor-β1, alkaline phosphatase and osteocalcin indicated that the level of differentiation of the cells grown on the different coatings increased in the order OCP<MgOCP<SrOCP.

• Effect of pulsed electromagnetic field exposure on adenosine receptors in rat brain.

  Authors: Katia Varani, Fabrizio Vincenzi, Martina Targa, Carmen Corciulo, Milena Fini, Stefania Setti, Ruggero Cadossi, Pier Andrea Borea

  Bioelectromagnetics. 10/2011;

  Different effects of pulsed electromagnetic field (PEMF) exposure on brain tissue have been described in pre-clinical models and in clinical settings. Nevertheless, the mechanism of action and theDifferent effects of pulsed electromagnetic field (PEMF) exposure on brain tissue have been described in pre-clinical models and in clinical settings. Nevertheless, the mechanism of action and the possible interaction with membrane receptors such as adenosine receptors (ARs) has not been investigated. The present study focused on the effect of PEMFs on A(1) and A(2A) ARs in the rat cerebral cortex and cortical neurons. Affinity and density of ARs were evaluated by means of saturation binding experiments while mRNA expression was investigated through retro-transcription polymerase chain reaction (RT-PCR). PEMF treatment of the intact rat cerebral cortex or cortical neurons at 1.5 mT mediated a transient and significant increase in A(2A) ARs after 4 h (2.0-fold increase) and 6 h (1.4- and 1.8-fold increase, respectively) of exposure. In addition, PEMF treatment of the rat cerebral cortex and rat cortical neurons at 3 mT upregulated A(2A) ARs after 2 h (2.0- and 2.2-fold increase, respectively) and 4 h (1.6- and 1.9-fold increase, respectively). The treatment of rat cortex membranes with PEMFs at 1.5 and 3 mT induced an increase in A(2A) AR density after 2 h (1.9- and 2.2-fold increase, respectively) and was constant at all incubation times investigated. In rat cortical neurons, mRNA levels of A(1) and A(2A) ARs were not affected by PEMF exposure for the times and intensities used. These results suggest that PEMF treatment has different biological effects in whole organs or cells in comparison with isolated membranes. Bioelectromagnetics. © 2011 Wiley Periodicals, Inc.

• Heparin-like heparan sulfate from rabbit cartilage.

  Authors: Alessandro Parra, Noemi Veraldi, Manuela Locatelli, Milena Fini, Lucia Martini, Giangiacomo Torri, Luca Sangiorgi, Antonella Bisio

  Glycobiology. 09/2011; 22(2):248-57.

  Glycosaminoglycans were extracted from both young rabbit growth plate (GRP) and articular (ART) cartilage tissues and enzymatically treated to selectively eliminate chondroitin sulfates andGlycosaminoglycans were extracted from both young rabbit growth plate (GRP) and articular (ART) cartilage tissues and enzymatically treated to selectively eliminate chondroitin sulfates and hyaluronic acid. The procedure avoided any fractionation step that could enrich the extract with over- or under-sulfated species. Isolated heparan sulfate (HS) was characterized by mono- and bidimensional nuclear magnetic resonance (NMR) spectroscopy to quantify their specific structural features and/or by mass spectrometry to establish the disaccharide composition. Both GRP and ART HSs, despite differing in their yield (GRP at least 100 times greater than ART), exhibited a surprisingly high degree of sulfation. Quantitative two-dimensional heteronuclear single-quantum coherence-NMR analysis of GRP HS revealed unusually high N-sulfated glucosamine and 2-O-sulfated iduronic acid contents, similar to heparin. The unique pentasaccharide sequence of the binding site for antithrombin was also detected in a significant amount. High-performance liquid chromatography mass spectrometry analysis of the enzymatic digests with a cocktail of heparin lyases of both cartilaginous HSs confirmed the NMR results. As well as the discovery of an unusual HS structure in the two different types of rabbit cartilage, the feasibility of the analytical method adopted here has been demonstrated within this study. Such a method can be used to isolate and analyze HS from both normal and pathologic tissues. Characterization of healthy and pathological HS structures will contribute to improve the understanding of diseases related to malfunctions of HS biosynthesis and/or metabolism.

• Nuclear phosphoinositides and their roles in cell biology and disease.

  Authors: Alberto M Martelli, Andrea Ognibene, Francesca Buontempo, Milena Fini, Daniela Bressanin, Kaoru Goto, James A McCubrey, Lucio Cocco, Camilla Evangelisti

  Critical reviews in biochemistry and molecular biology. 09/2011; 46(5):436-57.

  Since the late 1980s, a growing body of evidence has documented that phosphoinositides and their metabolizing enzymes, which regulate a large variety of cellular functions both in the cytoplasm andSince the late 1980s, a growing body of evidence has documented that phosphoinositides and their metabolizing enzymes, which regulate a large variety of cellular functions both in the cytoplasm and at the plasma membrane, are present also within the nucleus, where they are involved in processes such as cell proliferation, differentiation, and survival. Remarkably, nuclear phosphoinositide metabolism operates independently from that present elsewhere in the cell. Although nuclear phosphoinositides generate second messengers such as diacylglycerol and inositol 1,4,5 trisphosphate, it is becoming increasingly clear that they may act by themselves to influence chromatin structure, gene expression, DNA repair, and mRNA export. The understanding of the biological roles played by phosphoinositides is supported by the recent acquisitions demonstrating the presence in the nuclear compartment of several proteins harboring phosphoinositide-binding domains. Some of these proteins have functional roles in RNA splicing/processing and chromatin assembly. Moreover, recent evidence shows that nuclear phospholipase Cβ1 (a key phosphoinositide metabolizing enzyme) could somehow be involved in the myelodysplastic syndrome, i.e. a hematopoietic disorder that frequently evolves into an acute leukemia. This review aims to highlight the most significant and updated findings about phosphoinositide metabolism in the nucleus under both physiological and pathological conditions.

• Harmful lifestyles on orthopedic implantation surgery: a descriptive review on alcohol and tobacco use.

  Authors: Milena Fini, Gianluca Giavaresi, Francesca Salamanna, Francesca Veronesi, Lucia Martini, Monica De Mattei, Matilde Tschon

  Journal of bone and mineral metabolism. 09/2011; 29(6):633-44.

  Alcohol abuse and smoking habits have adverse effects on bone health and are a risk factor for osteoporosis, fractures and impaired fracture repair. Osteointegration processes around implantedAlcohol abuse and smoking habits have adverse effects on bone health and are a risk factor for osteoporosis, fractures and impaired fracture repair. Osteointegration processes around implanted biomaterials involve a coordinated cascade of complex events that are very similar to those occurring during fracture repair and require a suitable microenvironment and the coordinated action of cells and signal molecules. Therefore, diseases and harmful lifestyles that impair the normal bone healing process can reduce the success of implant surgery and may negatively influence the osteointegration of prostheses and implant devices for fracture fixation such as screws, nails and plates. Understanding the effects of harmful lifestyles on bone implant osteointegration is important for successful implant therapy, orthopedic reconstructive surgery and tissue-engineered-based therapies. However, the mechanisms by which smoking and alcoholism affect bone metabolism, bone mass and the balance of bone resorption and formation, also in the presence of an orthopedic implant, are not completely understood and remain inadequately elucidated. This review aims to analyze in vitro and in vivo studies regarding orthopedic implant integration in the presence of tobacco smoking and alcohol consumption with a focus on pathophysiology and local or systemic mechanisms of action on bone.

• Microbiological and pharmacological tests on new antibiotic-loaded PMMA-based composites for the treatment of osteomyelitis.

  Authors: Gianluca Giavaresi, Elisa Bertazzoni Minelli, Maria Sartori, Anna Benini, Tommaso Della Bora, Vittorio Sambri, Paolo Gaibani, Veronica Borsari, Francesca Salamanna, Lucia Martini, Nicolò Nicoli Aldini, Milena Fini

  Journal of orthopaedic research : official publication of the Orthopaedic Research Society. 08/2011; 30(3):348-55.

  Local antibiotic diffusion in rabbit femurs from two new PMMA-based and nail-shaped composites, enriched with β-tricalcium phosphate (P-TCP) and BaSO(4) or only with BaSO(4) (P-BaSO(4) ), and soakedLocal antibiotic diffusion in rabbit femurs from two new PMMA-based and nail-shaped composites, enriched with β-tricalcium phosphate (P-TCP) and BaSO(4) or only with BaSO(4) (P-BaSO(4) ), and soaked in a solution of gentamicin (G) and vancomycin (V) was studied. Nails were implanted into the intramedullary cavity of healthy and osteomyelitic femurs to study the resolution of infection and to quantify the antibiotic penetration into bone by microbiological, pharmacological, and histological tests. A significant progression of osteomyelitis was recorded 7 weeks after MRSA inoculation, whereas no bacteria were found in animals treated with antibiotic-loaded nails as confirmed by microbiology and histology (Smeltzer score). The release of both antibiotics from composites was high and prompt both in healthy and infected bone; the amount of V was higher than that of G in all bone samples. Antibiotics of both composites were still present in bone 3 weeks after nail implantation. The P-BaSO4 composite released a lower amount of antibiotics than did P-TCP. The G-V combination in vivo exerted a synergistic bactericidal effect, which was confirmed by microbiological, histological, and clinical results (no infection). These new porous PMMA composites, soaked in G-V solution in the operating room, might be an effective and useful drug delivery system for osteomyelitis treatment.

• Reply to comments of Carmona et al. to the article: Regenerative medicine for the treatment of musculoskeletal overuse injuries in competition horses.

  Authors: Paola Torricelli, Giuseppe Filardo, Elizaveta Kon, Milena Fini

  International orthopaedics. 07/2011;

• Immediate Fixed Implant Rehabilitation of the Atrophic Edentulous Maxilla after Bilateral Sinus Floor Augmentation: A 12-Month Pilot Study.

  Authors: Francesco Pieri, Nicolò Nicoli Aldini, Milena Fini, Claudio Marchetti, Giuseppe Corinaldesi

  Clinical implant dentistry and related research. 07/2011;

  Purposes: The aims of this study were to evaluate a surgical/prosthetic protocol for the immediate rehabilitation of the augmented edentulous maxilla, and to compare the outcomes of implants placedPurposes: The aims of this study were to evaluate a surgical/prosthetic protocol for the immediate rehabilitation of the augmented edentulous maxilla, and to compare the outcomes of implants placed in grafted (test group) versus native (control group) sites in the same patients. Materials and Methods: Twenty patients were included in the study. Each patient was treated with a bilateral sinus augmentation procedure using a 50:50 composite graft of autogenous mandibular bone and bovine hydroxyapatite. Four to 5 months later, 155 implants (90 test and 65 control) were placed and restored with screw-retained fixed definitive prostheses supported by titanium frameworks within 1 week. All patients were followed for 1 year. Implant stability quotient (ISQ) measurements and radiographic evaluation of the marginal bone resorption (MBR) were performed. Results: Two test implants failed in two patients, giving a cumulative 1-year success rate of 98.7%; the prostheses success rate was 100%. Insertion torque and ISQ values for test implants were significantly lower than those for control implants (unpaired t-test, p < .0001). The mean MBR around control and test implants at the 1-year evaluation were similar (0.47 ± 0.25 mm and 0.43 ± 0.21 mm, respectively). Conclusions: The combination of implants placed in sinus-grafted and native sites can be immediately loaded with a fixed full-arch prosthesis and yield short-term successful outcomes.

• Human dermal matrix scaffold augmentation for large and massive rotator cuff repairs: preliminary clinical and MRI results at 1-year follow-up.

  Authors: Roberto Rotini, Alessandro Marinelli, Enrico Guerra, Graziano Bettelli, Alessandro Castagna, Milena Fini, Elena Bondioli, Maurizio Busacca

  Musculoskeletal surgery. 06/2011; 95 Suppl 1:S13-23.

  The high incidence of recurrent tendon tears after repair of massive cuff lesions is prompting the research of materials aimed at mechanically or biologically reinforcing the tendon. Among theThe high incidence of recurrent tendon tears after repair of massive cuff lesions is prompting the research of materials aimed at mechanically or biologically reinforcing the tendon. Among the materials studied upto now, the extracellular matrix (ECM) scaffolds of human origin have proved to be the safest and most efficient, but the current laws about grafts and transplants preclude their use in Europe. In order to overcome this condition in 2006, we started a project regarding the production of an ECM scaffold of human origin which could be implanted in Europe too. In 2009, the clinical study began with the implantation of dermal matrix scaffolds in 7 middle-aged patients affected with large/massive cuff lesions and tendon degeneration. Out of 5 cases, followed for at least 1 year in which the scaffold was employed as an augmentation device, there were 3 patients with complete healing, 1 partial re-tear, and 1 total recurrence. The absence of adverse inflammatory or septic complications allows to continue this line of research with a prospective controlled study in order to define the real advantages and correct indications offered by scaffold application.

• In vivo preclinical evaluation of the influence of osteoporosis on the anchorage of different pedicle screw designs.

  Authors: Gianluca Giavaresi, Milena Fini, Roberto Giardino, Francesca Salamanna, Maria Sartori, Veronica Borsari, Silvia Spriano, Chiara M Bellini, Marco Brayda-Bruno

  European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. 05/2011; 20(8):1289-96.

  We investigate the anchorage of pedicle screws with different surface treatments in osteoporotic bone. Eight ewes were divided into two groups of four animals each: four sheep underwent bilateralWe investigate the anchorage of pedicle screws with different surface treatments in osteoporotic bone. Eight ewes were divided into two groups of four animals each: four sheep underwent bilateral ovariectomy (OVX Group), whereas the operation was simulated in the remaining group (SHAM Group). Eighteen months after the first operation, the Dynesys(®) System was fitted to the sheep using pedicle screws with three different surface treatments: untreated, rough blasted (uncoated) and bioactive coated (bioactive). Uncoated screws showed a significantly higher bone ingrowth value compared with the untreated screws in the OVX group (9.3%, p < 0.005) and a significantly lower bone ingrowth value in the SHAM group (-11.0%, p < 0.05). Furthermore, the bioactive pedicle screws had a significant lower bone ingrowth value than the untreated screws in the SHAM group (-12.1%, p < 0.05). These results suggest that both tested surface treatments of pedicular screws may provide an advantage in terms of bone quality and osseointegration, when implanted in osteoporotic vertebrae.

• Pietro Loreta and his contribution to surgery in the 19th century.

  Authors: Nicolò Nicoli Aldini, Milena Fini, Roberto Giardino

  The American surgeon. 03/2011; 77(3):290-6.

  Pietro Loreta (1831 to 1889), head of surgery at the University of Bologna, Italy, is at present a little-known name. However, in the field of surgery in the second half of the 19th century, hisPietro Loreta (1831 to 1889), head of surgery at the University of Bologna, Italy, is at present a little-known name. However, in the field of surgery in the second half of the 19th century, his contributions to various areas, especially that of bladder stone treatment and gastric surgery, aroused great interest also at the international level. This survey focuses on both of these subjects that are particularly indicative of Loreta's activity. While he was trying to improve the operation of perineal cystotomy, which was about to be abandoned, he was faced with the new frontier of gastrointestinal tract surgery. Surgery was in rapid transformation, and the practice of a general surgeon still encompassed the domains of different surgical specialties, which would develop individually afterward. Loreta was a pupil of the outstanding surgeon Francesco Rizzoli and some of his pupils such as Alessandro Codivilla and Bartolo Nigrisoli became heads of surgery. His attitude of caution, that he recommended in his writings, is more remarkable considering his problematic nature and might be the most significant and original trait of Loreta's personality.