Zoledronic acid at subtoxic dose extends osteoblastic stage span of primary human osteoblasts.

OBJECTIVE: This study aimed to check the effect of zoledronic acid (ZA) at subtoxic dose on human osteoblasts (HOs) in terms of cell viability, apoptosis occurrence, and differentiation induction. ZA belongs to the family of bisphosphonates (BPs), largely used in the clinical practice for the treatment of bone diseases, often associated with jaw osteonecrosis onset. Their pharmacological action consists in the direct block of the osteoclast-mediated bone resorption along with indirect action on osteoblasts. MATERIALS AND METHODS: HOs were treated choosing the highest limit concentration (10(-5) M) which does not induce toxic effects. Live/dead staining, flow cytometry, mitochondrial membrane potential assay, osteocalcin western blotting, gp38 RT-PCR, collagen type I, PGE2, and IL-6 ELISA assays were performed. RESULTS: Similar viability level between control and ZA-treated samples is found along with no significant increase of apoptotic and necrotic cells in ZA-treated sample. To establish if an early apoptotic pathway was triggered, Bax expression and mitochondrial membrane potential were evaluated finding a higher protein expression in control sample and a good integrity of mitochondrial membrane in both experimental points. Type I collagen secretion and alkaline phosphatase (ALP) activity appear increased in ZA-treated sample, osteocalcin expression level is reduced in ZA-treated cells, whereas no modifications of gp38 mRNA level are evidenced. No statistical differences are identified in PGE2 secretion level whereas IL-6 secretion is lower in ZA-treated HOs with respect to control ones. CONCLUSIONS: These results highlight that ZA, delaying the osteoblastic differentiation process versus the osteocytic lineage, strengthens its pharmacological activity enhancing bone density. CLINICAL RELEVANCE: The knowledge of ZA effects on osteoblasts at subtoxic dose allows to improve therapeutic protocols in order to strengthen drug pharmacological activity through a combined action on both osteoclastic and osteoblastic cells.

Traditional endodontic surgery versus modern technique: a 5-year controlled clinical trial.

In this study, we compared outcomes of traditional apicoectomy versus modern apicoectomy, by means of a controlled clinical trial with a 5-year follow-up. The study investigated 938 teeth in 843 patients. On the basis of the procedure performed, the teeth were grouped in 3 groups. Differences between the groups were the method of osteotomy (type of instruments used), type of preparation of retrograde cavity (different apicoectomy angles and instruments used for root-end preparation), and root-end filling material used (gray mineral trioxide aggregate or silver amalgam). Outcome (tooth healing) was estimated after 1 and 5 years, postoperatively. Clinical success rates after 1 year were 67% (306 teeth), 90% (186 teeth), and 94% (256 teeth) according to traditional apicoectomy (group 1), modern microsurgical apicoectomy using burns for osteotomy (group 2) or using piezo-osteotomy (group 3), respectively. After 1 year, group comparison results were statistically significant (P < 0.0001). Linear trend test was also statistically significant (P < 0.0001), pointing out larger healing from group 1 to group 3. After 5 years, teeth were classified into 2 groups on the basis of root-end filling material used. Clinical success was 90.8% (197 teeth) in the silver amalgam group versus 96% (309 teeth) in the mineral trioxide aggregate group (P < 0.00214). Multiple logistic regression analysis found that surgical technique was independently associated to tooth healing. In conclusion, modern apicoectomy resulted in a probability of success more than 5 times higher (odds ratio, 5.20 [95% confidence interval, 3.94-6.92]; P < 0.001) compared with the traditional technique.

Immediate function of partial fixed rehabilitation with axial and tilted implants having intrasinus insertion.

Implant-supported rehabilitation of the posterior maxilla could be challenging because hyperpneumatization of the maxillary sinus might reduce the bone height. In this study, the authors report preliminary results of a new treatment modality for the partial fixed rehabilitation of posterior maxilla with immediate function by using 1 anterior axial implant and 1 posterior tilted implant with intrasinus mesial insertion. From 2009 to 2011, 10 patients (6 women and 4 men) with missing upper premolars and molars were recruited and treated according to this protocol. Each patient received a partial fixed bridge supported by 1 axial anterior implant and 1 posterior implant placed with a 30-degree mesial inclination and intrasinus insertion. Autologous bone was positioned to fill the maxillary sinus cavity and to cover the exposed implant surface after elevation of the anterior sinus membrane. A prosthesis with immediate function was positioned within 3 hours, whereas a CAD/CAM final restoration was delivered 6 months later. Follow-ups at 6 and 12 months, and then annually, were scheduled. At each follow-up, plaque level and bleeding scores were assessed, and radiographic evaluation of marginal bone level change was performed at 1 year. The patients were followed up for a mean of 50 months (range, 42-57 mo). No implants were lost, and all prostheses were stable and functional, reporting 100% of implant and prosthetic success rates. After 1 year, bone loss had a mean (SD) of 1.0 (0.4) and 0.9 (0.5) mm for axial and tilted implants, respectively, with no statistically significant differences between them (P > 0.05). The preliminary results suggest that this approach could allow the rehabilitation of posterior maxilla with immediate function in case of reduced bone volume, representing an alternative technique to bone grafting, short implants, and zygomatic or pterygoid implants.

Ultrasonic versus drills implant site preparation: a histologic analysis in bovine ribs.

PURPOSE: Ultrasonic surgery is a recently developed system for cutting bone with microvibrations. The aim of the current study was a histologic comparison between conventional drills versus ultrasonic surgery devices in implant bed preparation. METHODS: Ten bovine ribs were used, and a total of 100 perforations were randomly performed: half (n = 50) (group A) of the perforations were done through conventional drills using a single cylindrical bur (Bone System, Milan, Italy), 13 mm in height and 2 mm in width at a speed of 400 rpm, and the other half (n = 50) (group B) using an ultrasonic device (Surgysonic; Esacrom, Imola Italy), mounted with a diamond-coated cylindrical tip. After implant sites' preparation, the ribs were immediately stored in 10% buffered formalin and processed to obtain thin ground sections. RESULTS: At higher magnification, microcracks at the interface were detected. In group A, they were numerous and showed a thickness and depth ranging from 20 to 120 µm and from 500 to 1000 µm, respectively. In group B, very few or no microcracks were present. Statistically significant differences were found in the microcracks density in the cortical bone but not in the cancellous bone. CONCLUSIONS: The findings from this study suggest that ultrasonic implant site preparation showed a higher performance in terms of accuracy and uniformity of the osteotomy cut, compared with conventional rotary instruments. Further studies should be conducted to understand whether a smooth, congruent implant bed able to retain fine bone structures may affect the early phases of bone healing and therefore improve osseointegration.

Hemostasis control in dental extractions in patients receiving oral anticoagulant therapy: an approach with calcium sulfate.

The aim of this study was to evaluate the use of calcium sulfate (CaS) as a hemostatic agent after tooth extraction in patients with anticoagulant drug therapy. A total of 30 patients undergoing anticoagulant therapy (22 women and 8 men) with a mean age of 54.6 years (SD = 9.2 years), needing dental extractions, were selected for this study. They were divided into 2 groups, control (group 1) and test (group 2), in a randomized way. In group 1 patients, the postextraction socket was managed with obliterative suture only. Group 2 patients were treated with CaS placed into the postextraction sockets. All the patients did not interrupt the anticoagulant therapy during the dental treatment. The healing pattern was found to be approximately similar in all treatment groups, showing significant improvement at each consecutive visit. However, a statistically significant difference in the adequate hemostasis was evident between groups 1 and 2 (P = 0.0056). The use of CaS helped to control the bleeding from inside the socket, producing instantly a very good hemostasis. Further studies are necessary to confirm the simplicity, possibilities, and limits of the proposed procedure.

Relationship between the surface energy and the histologic results of different titanium surfaces.

The aim of this study was to evaluate, through in vitro and in vivo studies, the existence of a relationship between surface energy, for wettability, and the clinical behavior of dental implants with different surfaces, one with a surface treated by sandblasting with titanium oxide microparticles followed by acid-etching treatment (experimental group) and another with a machined surface (control group). For the in vitro tests, a total of 30 titanium disks (15 disks for each group) were evaluated by scanning electron microscopy and dispersive energy spectroscopy and for surface roughness and wettability. For the in vivo tests, a total of 24 implants (12 implants for each group) were inserted in the tibiae of 6 rabbits and were removed after 30 and 60 days for histologic analysis. The results showed that the implants with the experimental surface presented a low wettability, and it also resulted in highly stimulated new bone formation in vivo, when compared with the control group dental implant. As for the bone formation, differences between the different surfaces seemed evident, both in quantity and in quality, as implants from the experimental group showed a higher new bone deposition than that from the control group. Thus, in vitro and in vivo tests demonstrated an excellent biologic response of the surfaces treated by sandblasting with microparticles of titanium oxide followed by acid etching.

Equine and porcine bone substitutes in maxillary sinus augmentation: a histological and immunohistochemical analysis of VEGF expression.

The aim of this work was to investigate the morphological structure and the expression of vascular endothelial growth factor (VEGF) after maxillary sinus augmentation through equine and porcine bone substitutes in humans. Ten patients showing edentulous posterior maxilla underwent maxillary sinus augmentation through particulate equine bone substitute and 10 patients through particulate porcine bone substitute. At the moment of implants insertion, 6 months after grafting, bone specimens were withdrawn and processed for morphological and immunohistochemical analyses. Notwithstanding the almost comparable clinical performances of both bone substitutes, histological results showed a better integration when an equine bone substitute was used compared to a porcine one. In particular, evident signs of particles resorption were observed in equine bone substitute group specimens compared to porcine ones. Immunohistochemical analysis showed a statistically significant increase of VEGF expression in equine compared to porcine bone substitute group specimens. These results showed both bone substitutes to achieve comparable clinical performance, indicating their successful use for bone regenerative procedures. However, in the same experimental time, equine group specimens showed evident resorption phenomena, whereas no or little signs of resorption were evident in the porcine group specimens. However, a more rapid and intense vascularization was achieved in equine bone substitute group, as demonstrated by immunohistochemical analysis for VEGF expression. Even if differences in vascularization significantly affect the clinical performance of a heterologous bone substitute, its ability to be resorbed is also very important in influencing long-term integration and long-term predictability of implant-prosthetic rehabilitation in regenerated sites.

Role of amniotic fluid mesenchymal cells engineered on MgHA/collagen-based scaffold allotransplanted on an experimental animal study of sinus augmentation.

OBJECTIVES: The present research has been performed to evaluate whether a commercial magnesium-enriched hydroxyapatite (MgHA)/collagen-based scaffold engineered with ovine amniotic fluid mesenchymal cells (oAFMC) could improve bone regeneration process in vivo. MATERIALS AND METHODS: Bilateral sinus augmentation was performed on eight adult sheep in order to compare the tissue regeneration process at 45 and 90 days after implantation of the oAFMC-engineered scaffold (Test Group) or of the scaffold alone (Ctr Group). The process of tissue remodeling was analyzed through histological, immunohistochemical, and morphometric analyses by calculating the proliferation index (PI) of oAFMC loaded on the scaffold, the total vascular area (VA), and vascular endothelial growth factor (VEGF) expression levels within the grafted area. RESULTS: MgHA/collagen-based scaffold showed high biocompatibility preserving the survival of oAFMC for 90 days in grafted sinuses. The use of oAFMC increased bone deposition and stimulated a more rapid angiogenic reaction, thus probably supporting the higher cell PI recorded in cell-treated sinuses. A significantly higher VEGF expression (Test vs. Ctr Group; p = 0.0004) and a larger total VA (p = 0.0006) were detected in the Test Group at 45 days after surgery. The PI was significantly higher (p = 0.027) at 45 days and became significantly lower at 90 days (p = 0.0007) in the Test Group sinuses, while the PI recorded in the Ctr Group continued to increase resulting to a significantly higher PI at day 90 (CTR day 45 vs. CTR day 90; p = 0.022). CONCLUSIONS: The osteoinductive effect of a biomimetic commercial scaffold may be significantly improved by the presence of oAFMC. CLINICAL RELEVANCE: The amniotic fluid mesenchymal cell (AFMC) may represent a novel, largely and easily accessible source of mesenchymal stem cells to develop cell-based therapy for maxillofacial surgery.

Histological evaluation of fresh frozen bone integration at different experimental times.

The aim of this work was to investigate, through histological evaluation, the in vivo behavior of fresh frozen bone (FFB) used as particulate bone substitute in intraoral regenerative procedures. A total of 10 patients (group 1) received particulate FFB graft for bone regeneration in postextractive sockets, and 10 (group 2) underwent maxillary sinus augmentation by using the same bone substitute as filling. Fresh frozen bone was supplied from the Tissue Bank of the Veneto Region, Treviso Section.Healing was uneventful for all the patients and was monitored by periodical radiographs. Patients were scheduled for implant insertion according to the radiographic aspect. However, the mean healing time for group 1 was 45 days, whereas for group 2 patients, it was 100 days. At the moment of implant insertion, bone specimens were collected at the site of implant placement, from both groups and processed for histological analysis.Histological analysis after hematoxylin-eosin staining obtained from group 1 patients showed the presence of newly formed bone tissue, still well distinguishable from the grafted bone substitute. In samples from group 2 patients, a better integration could be recognized associated with active bone remodeling phenomena.These results showed a good integration of the considered FFB graft within the host tissue both at 45 and 100 days after grafting, displaying this biomaterial as suitable for preimplant regenerative procedures.

A comparison of bovine bone and hydroxyapatite scaffolds during initial bone regeneration: an in vitro evaluation.

OBJECTIVES: To evaluate the different behavior of 3-dimensional biomaterial scaffolds-Bovine Bone (BB; Bio-Oss) and Hydroxyapatite (HA; ENGIpore)-during initial bone healing and development. MATERIALS AND METHODS: Human dental papilla stem cells (hDPaSCs) were selected with FACsorter cytofluorimetric analysis, cultured with osteogenic medium, and analyzed with Alizarin red stained after differentiation. The obtained osteoblast-like cells (OCs) were cultured with BB and HA. alkaline phosphatase (ALP), OC, MEPE, and runt-related transcription factor 2 (RUNX2) expression markers were investigated performing Western blot and reverse transcription-polymerase chain reaction (RT-PCR) analysis. After 40 days, samples were analyzed by light and electron microscopy. RESULTS: All the samples showed high in vitro biocompatibility and qualitative differences of OCs adhesion. RT-PCR and Western blot data exhibited similar marker rate, but ALP, OC, MEPE, and RUNX2expression, during initial healing and bone regeneration phase, was higher and faster in human dental papilla onto BB than in HA scaffolds. In biomaterials growth, RUNX2 seems to play an important role as a key regulator in human OCs from dental papilla bone development. CONCLUSION: Different surface BB scaffold characteristics seem to play a critical role in OCs differentiation showing different time of bone regeneration morphological characteristics as well as higher and faster levels of all observed markers.

Group IV phospholipase A(2)alpha controls the formation of inter-cisternal continuities involved in intra-Golgi transport.

The organization of intra-Golgi trafficking and the nature of the transport intermediates involved (e.g., vesicles, tubules, or tubular continuities) remain incompletely understood. It was recently shown that successive cisternae in the Golgi stack are interconnected by membrane tubules that form during the arrival of transport carriers from the endoplasmic reticulum. Here, we examine the mechanisms of generation and the function of these tubules. In principle, tubule formation might depend on several protein- and/or lipid-based mechanisms. Among the latter, we have studied the phospholipase A(2) (PLA(2))-mediated generation of wedge-shaped lysolipids, with the resulting local positive membrane curvature. We show that the arrival of cargo at the Golgi complex induces the recruitment of Group IVA Ca(2+)-dependent, cytosolic PLA(2) (cPLA(2)alpha) onto the Golgi complex itself, and that this cPLA(2)alpha is required for the formation of the traffic-dependent intercisternal tubules and for intra-Golgi transport. In contrast, silencing of cPLA(2)alpha has no inhibitory effects on peri-Golgi vesicles. These findings identify cPLA(2)alpha as the first component of the machinery that is responsible for the formation of intercisternal tubular continuities and support a role for these continuities in transport through the Golgi complex.

Stemness characteristics and osteogenic potential of sheep amniotic epithelial cells.

We set out to characterize stemness properties and osteogenic potential of sheep AEC (amniotic epithelial cells). AEC were isolated from 3-month-old fetuses and expanded in vitro for 12 passages. The morphology, surface markers, stemness markers and osteogenic differentiation were inspected after 1, 6 and 12 passages of expansion, with an average doubling time of 24 h. AEC clearly expressed the stemness markers Oct-3/4 (octamer-binding protein-3/4), Nanog, Sox2 and TERT (telomerase reverse transcriptase) and displayed low levels of global DNA methylation. Culture had moderate effects on cell conditions; some adhesion molecules progressively disappeared from the cell surface, and the expression of Sox2 and TERT was slightly reduced while Nanog increased. No changes occurred in the levels of DNA methylation. Cells organized in 3D spheroids were used for IVD (in vitro differentiation). Within these structures the cells developed a complex intercellular organization that involved extensive intercellular coupling despite continuous cell migration. Marked deposition of calcein in the ECM (extracellular matrix), increased ALP (alkaline phosphatase) activity, expression of bone-related genes (osteocalcin) and the matrix mineralization shown by Alizarin Red staining demonstrate that AEC can undergo rapid and extensive osteogenic differentiation. AEC introduced in experimental bone lesions survived in the site of implantation for 45 days and supported consistent bone neoformation, thus showing promising potential applications in osteogenic regenerative medicine.

The role of inducible nitric oxide synthase and haem oxygenase 1 in growth and development of dental tissue'.

In this study, the activity of the antioxidant enzyme network was assessed spectrophotometrically in samples of dental pulp and dental papilla taken from third-molar gem extracts. The production of nitric oxide by the conversion of l-(2,3,4,5)-[3H] arginine to l-(3H) citrulline, the activity of haem oxygenase 1 (HO-1) through bilirubin synthesis and the expression of inducible nitric oxide synthase (iNOS), HO-1 proteins and messenger RNA by Western blot and reverse-transcribed polymerase chain reaction were also tested. The objective of this study was to evaluate the role of two proteins, iNOS and HO-1, which are upregulated by a condition of oxidative stress present during dental tissue differentiation and development. This is fundamental for guaranteeing proper homeostasis favouring a physiological tissue growth. The results revealed an over-expression of iNOS and HO-1 in the papilla, compared with that in the pulp, mediated by the nuclear factor kappa B transcription factor activated by the reactive oxygen species that acts as scavengers for the superoxide radicals. HO-1, a metabolically active enzyme in the papilla, but not in the pulp, seems to inhibit the iNOS enzyme by a crosstalk between the two proteins. We suggest that the probable mechanism through which this happens is the interaction of HO-1 with haem, a cofactor dimer indispensible for iNOS, and the subsequent suppression of its metabolic activity.

Immunohistochemical analysis of matrix metalloproteinase-9, vascular endothelial growth factor, bone sialoprotein and i-nitric oxide synthase in calvaria vs. iliac crest bone grafts.

OBJECTIVES: The aim of this study was to investigate, in parallel to clinical and histological modifications, the expression of specific proteins involved in different extraoral autologous bone grafts integration in humans. MATERIAL AND METHODS: Patients needing oral rehabilitation of posterior maxilla, with inadequate bone volume for implant placement, received bone grafts from calvaria (Group 1) and iliac crest (Group 2), respectively. From five patients from each group, with a total of 10 subjects, bone biopsy specimens were collected at two different experimental time points: at bone blocks withdrawal for grafting (T0), from donor sites, and after 4 months, from reconstructed sites. Samples were processed for light microscope and immunohistochemical analyses to evaluate MMP9, VEGF, BSP, iNOS expression. RESULTS: Morphological analysis of T0 calvaria evidenced areas of extracellular matrix, uniformly stained and organized in concentric mineralized lamellae edging few vascular canals, while T0 iliac crest showed greater cellularity compared to calvaria, with rare mineralized areas, surrounding wide bone marrow lacunae. In T1, Group 1 samples showed large areas of extracellular matrix, uniformly stained, at the same time as Group 2 samples disclosed few areas of mineralized tissue. Although no significant differences were found in proteins expression among calvaria and iliac crest T0 samples, MMP9, VEGF and BSP expression at T1 were discovered higher in Group 1 samples than in Group 2 ones, while iNOS expression increased in Group 2 samples compared to the others. In any group, molecules expression increased passing from T0 to T1. CONCLUSION: These findings suggested that, even though clinically both extraoral sources of autologous bone could be considered suitable for grafting in case of large oral rehabilitation, some differences might be detected microscopically and biologically. Calvaria bone graft seemed to enhance not only the quantity of bone tissue at the defect site, but also its quality, better than iliac crest bone do. Then, while both grafts appeared to promote a suitable neoangiogenesis, as showed by morphological analysis and by MMP9 and VEGF expression, in terms of new bone formation and lack of occurrence of inflammatory events, calvaria could be considered a more suitable donor site for bone grafts.

Five-year prospective clinical study of posterior three-unit zirconia-based fixed dental prostheses.

This prospective clinical trial aimed at evaluating the clinical performance of three-unit posterior zirconia fixed dental prostheses (FDPs) after 5 years of clinical function. Thirty-seven patients received 48 three-unit zirconia-based FDPs. The restorations replaced either a premolar or a molar. Specific inclusion criteria were needed. Tooth preparation was standardized. Computer-aided design/computer-assisted manufacturing frameworks with a 9-mm(2) cross section of the connector and a 0.6-mm minimum thickness of the retainer were made. The restorations were luted with resin cement. The patients were recalled after 1, 6, 12, 24, 36, 48, and 60 months. The survival and success of the ceramics and zirconia were evaluated. The technical and aesthetic outcomes were examined using the United States Public Health Service criteria. The biologic outcomes were analyzed at abutment and contralateral teeth. Descriptive statistics were performed. All FDPs completed the study, resulting in 100% cumulative survival rate and 91.9% and 95.4% cumulative success rates for patients wearing one and two FDPs, respectively. No losses of retention were recorded. Forty-two restorations were rated alpha in all measured parameters. A minor chipping of the ceramics was detected in three restorations. No significant differences between the periodontal parameters of the test and control teeth were observed. Five-year clinical results proved that three-unit posterior zirconia-based FDPs were successful in the medium term for both function and aesthetic. Zirconia can be considered a promising substitute of metal frameworks for the fabrication of short-span posterior prostheses.

The prognosis of myofascial pain syndrome (MPS) during a fixed orthodontic treatment.

Among treatments in the literature for myofascial pain syndrome (MPS), the most reliable therapies in dentistry are spray and stretch, and, although less frequently used, anesthetic injection. Adult MPS subjects are often treated using fixed orthodontic therapy for resolution of malocclusion. There is no clarity in the literature on the prognosis of MPS during orthodontic therapy. The purpose of this study was to analyze the prognosis of MPS during orthodontic treatment of subjects with malocclusion, initially diagnosed as having MPS. The analysis covered the medical records of 91 young adult Caucasians scheduled for orthodontic treatment for various malocclusions. Thirty-seven of the patients were initially diagnosed as also having MPS (T0). Thirty patients began the orthodontic treatment and were recalled for a re-evaluation of MPS after dental alignment and dental class correction was achieved (T1). A wait-and-see strategy was applied in seven subjects who were included as the control subjects. They received no treatment for MPS. At T1, a statistically significant decrease was observed in the study group in the presence of any clicking or creaking noises from the jaw joint, a significant jaw joint and jaw muscle pain reduction, and a quality of life improvement. Among patients who were depressed at the beginning of treatment, the majority felt better at the follow-up evaluation. On muscular palpation, a statistically significant decrease was found on the visual analogic scale value of the middle fibers of the temporalis muscle, temporalis tendon, clavicular and sternal division of the sternocleidomastoid muscle, masseter muscles, and posterior cervical muscles. The temporalis and the masseter muscles showed a significant decrease in the number of subjects with trigger points (TrPs) in all areas in the study group, after treatment. The digastric and sternocleidomastoid muscles also showed a significant reduction in the number of subjects with TrPs. Subjects with MPS and malocclusion were treated using a fixed orthodontic treatment. They showed improvement, although no resolution, in the signs and symptoms of MPS, compared with the untreated control group.

Implant therapy in irradiated patients.

In this multicenter study, submerged implants were prospectively followed to evaluate their long-term prognosis in irradiated patients. In a total of 77 patients treated for oral or neck cancer, 188 implants were consecutively placed. After a healing period, the successfully integrated implants were restored with 69 removable and 38 fixed restorations. The implants cumulative survival and success rates were evaluated over a period of at least 36 months. In addition, cumulative success rates were calculated for implant subgroups divided per implant site (mandible or maxilla), radiation dosage, and the time interval between the last irradiation and implant placement. During the healing period, 20 implants did not successfully integrate, whereas 168 implants were classified as success (including both survival and success rates). The analysis of implant subgroups showed slightly more favorable cumulative success rate for mandibular implants (98.4%) compared with maxillary implants (57.1%) and clearly better success rate for a radiation dosage minor of 50-Gy doses. A time greater than 12 months as interval between last irradiation and implant placement seems not to promote better clinical results.

Long-term evaluation of maxillary reconstruction by iliac bone graft.

The aim of this study was to analyze histologic and immunohistochemical modifications taking place in maxillary sites reconstructed by iliac crest bone grafts, 4 months (T1) and 10 years (T2) after grafting, in comparison to native iliac crest bone (T0).By light microscopy, T1 samples showed well-organized osteoblasts and extracellular matrix (ECM), and surrounding areas of connective tissue where a discrete number of blood vessels can be distinguished. Samples obtained from reconstructed areas after a long period of follow-up (T2) were characterized by uniform mineralized ECM with cavities containing osteocytes, whereas T0 samples disclosed both mineralized matrix and bone marrow. Matrix metalloproteinase 2 (MMP-2), vascular endothelial growth factor (VEGF), inducible nitric oxide synthase (iNOS), and bone sialoprotein (BSP) expressions were investigated by immunohistochemical analysis. Both MMP-2 and VEGF showed significantly increased expression in T1, with respect to T0, and lowered in T2. Otherwise, BSP expression, which was elevated in native iliac crest bone (T0), was deeply decreased in T1 and T2 samples. Moreover, changes in iNOS expression and in apoptotic cell nuclei percentages (TUNEL analysis) seemed to have a similar trend, increasing in T1 and lowering in T2.After a period of 4 months, iliac crest bone graft-reconstructed sites show mineralizing nuclei not strongly represented, as suggested by BSP lower expression, whereas new blood vessel proliferation and active remodeling phenomena are developing. After a long period from the grafting (T2), BSP expression decreases along with MMP-2, VEGF, and iNOS, suggesting the presence of only weak arrangement phenomena of the graft.

Genetics of syndromic and nonsyndromic cleft lip and palate.

Cleft of the lip with or without cleft palate (CL/P) represents one of the commonest congenital malformations in Western countries. Based on their association with specific malformative patterns or their presence as isolated defects, CL/P can be classified as syndromic and nonsyndromic, respectively. Both forms of CL/P are characterized by a strong genetic component. Syndromic forms are in many cases due to chromosomal aberrations or monogenic diseases. Among these, the Van der Woude syndrome, caused by mutation of the IRF6 gene, represents the commonest form of syndromic CL/P, accounting for about 2% of all cases. On the other hand, nonsyndromic CL/P is a multifactorial disease derived by the interaction between genetic and environmental factors. In recent years, great efforts have been made to identify the genes involved in the susceptibility to nonsyndromic CL/P and to disclose their relationship with specific environmental risk factors, to get information about the pathogenic mechanism leading to the malformation. In this article, we will review the most recent findings about the genes involved in the pathogenesis of syndromic and nonsyndromic CL/P, to provide information about the opportunity in the future to use specific genetic testing for the identification of at-risk mothers and the prevention of the disease based on a personalized approach.

Rapid expansion of the palate with a new surgical technique.

After briefly reviewing the literature concerning palatal expansion, a new technique combining surgical and medical orthodontic treatment is described. The technique, which entails detaching the nasal septum, is particularly appropriate in oral-breathing patients. Sixty-one patients (aged 10-32 years) were included in the study. The technique, which has low morbidity, gave good short- and long-term results.