Soft Tissue Stability around Single Implants Inserted to Replace Maxillary Lateral Incisors: A 3D Evaluation.

Purpose. To evaluate the soft tissue stability around single implants inserted to replace maxillary lateral incisors, using an innovative 3D method. Methods. We have used reverse-engineering software for the superimposition of 3D surface models of the dentogingival structures, obtained from intraoral scans of the same patients taken at the delivery of the final crown (S1) and 2 years later (S2). The assessment of soft tissues changes was performed via calculation of the Euclidean surface distances between the 3D models, after the superimposition of S2 on S1; colour maps were used for quantification of changes. Results. Twenty patients (8 males, 12 females) were selected, 10 with a failing/nonrestorable lateral incisor (test group: immediate placement in postextraction socket) and 10 with a missing lateral incisor (control group: conventional placement in healed ridge). Each patient received one immediately loaded implant (Anyridge®, Megagen, Gyeongbuk, South Korea). The superimposition of the 3D surface models taken at different times (S2 over S1) revealed a mean (±SD) reduction of 0.057 mm (±0.025) and 0.037 mm (±0.020) for test and control patients, respectively. This difference was not statistically significant (p = 0.069). Conclusions. The superimposition of the 3D surface models revealed an excellent peri-implant soft tissue stability in both groups of patients, with minimal changes registered along time.

CDKL5 knockout leads to altered inhibitory transmission in the cerebellum of adult mice.

Mutations in the X-linked cyclin-dependent kinase-like 5 gene (CDKL5) are associated to severe neurodevelopmental alterations including motor symptoms. In order to elucidate the neurobiological substrate of motor symptoms in CDKL5 syndrome, we investigated the motor function, GABA and glutamate pathways in the cerebellum of CDKL5 knockout female mice. Behavioural data indicate that CDKL5-KO mice displayed impaired motor coordination on the Rotarod test, and altered steps, as measured by the gait analysis using the CatWalk test. A higher reduction in spontaneous GABA efflux, than that in glutamate, was observed in CDKL5-KO mouse cerebellar synaptosomes, leading to a significant increase of spontaneous glutamate/GABA efflux ratio in these animals. On the contrary, there were no differences between groups in K(+) -evoked GABA and glutamate efflux. The anatomical analysis of cerebellar excitatory and inhibitory pathways showed a selective defect of the GABA-related marker GAD67 in the molecular layer in CDKL5-KO mice, while the glutamatergic marker VGLUT1 was unchanged in the same area. Fine cerebellar structural abnormalities such as a reduction of the inhibitory basket 'net' estimated volume and an increase of the pinceau estimated volume were also observed in CDKL5-KO mice. Finally, the BDNF mRNA expression level in the cerebellum, but not in the hippocampus, was reduced compared with WT animals. These data suggest that CDKL5 deletion during development more markedly impairs the establishment of a correct GABAergic cerebellar network than that of glutamatergic one, leading to the behavioural symptoms associated with CDKL5 mutation.

Direct metal laser sintering titanium dental implants: a review of the current literature.

Statement of Problem. Direct metal laser sintering (DMLS) is a technology that allows fabrication of complex-shaped objects from powder-based materials, according to a three-dimensional (3D) computer model. With DMLS, it is possible to fabricate titanium dental implants with an inherently porous surface, a key property required of implantation devices. Objective. The aim of this review was to evaluate the evidence for the reliability of DMLS titanium dental implants and their clinical and histologic/histomorphometric outcomes, as well as their mechanical properties. Materials and Methods. Electronic database searches were performed. Inclusion criteria were clinical and radiographic studies, histologic/histomorphometric studies in humans and animals, mechanical evaluations, and in vitro cell culture studies on DMLS titanium implants. Meta-analysis could be performed only for randomized controlled trials (RCTs); to evaluate the methodological quality of observational human studies, the Newcastle-Ottawa scale (NOS) was used. Results. Twenty-seven studies were included in this review. No RCTs were found, and meta-analysis could not be performed. The outcomes of observational human studies were assessed using the NOS: these studies showed medium methodological quality. Conclusions. Several studies have demonstrated the potential for the use of DMLS titanium implants. However, further studies that demonstrate the benefits of DMLS implants over conventional implants are needed.

Intrusive luxation of primary upper incisors and sequelae on permanent successors: a clinical follow-up study.

AIM: The purpose of this report is to evaluate the epidemiological aspects of intrusion that occur against upper incisors in primary dentition, to determine the statistic correlation of developmental disturbances to permanent teeth in relation to age of children at the time of trauma. MATERIALS AND METHODS: A retrospective study was performed based on radiographic and clinical data of 34 intruded incisors in 30 patients aged between 12 and 60 months. Baseline data were collected in a questionnaire designed following the guidelines of the IADT-Italy. The descriptive statistical analysis between the different variables was performed with the Chi-squared test and the level of significance was set at 5%. The following parameters were considered: gender, age of patient at the time of injury, emergency treatment, clinical signs (vitality, mobility, spontaneous pain, colour change), presence of complications, degree of spontaneous re-eruption and possible developmental disorders to the following tooth. RESULTS: Intrusive luxation is not statistically related to gender. During the first 6-month follow-ups, 20 incisors belonging to 12 subjects aged between 12-24 months at the time of intrusion exhibited pulpal necrosis. The highest rate of total spontaneous re-eruption occurred in incisors intruded at 12-24 months. The likelihood of spontaneous re-eruption decreased with the child's age. A significant correlation between mobility at clinical follow-up and developmental disorders in permanent teeth was found, whereas a statistical correlation between age of patient at the time of trauma and sequelae was not pointed out, even if 17 primary incisors intruded at 12-24 months did not develop an arrest of root formation. CONCLUSION: The most traumatic intrusions in primary dentition occurs between 12 and 24 months of age, the most common cause being fall while walking. Intruded incisors with moderate mobility developed enamel hypoplasia and ectopic eruption. There was no significant correlation between age at the time of intrusion and type of subsequent developmental disturbances.

Influence of biological matrix and artificial electrospun scaffolds on proliferation, differentiation and trophic factor synthesis of rat embryonic stem cells.

Two-dimensional vs three-dimensional culture conditions, such as the presence of extracellular matrix components, could deeply influence the cell fate and properties. In this paper we investigated proliferation, differentiation, survival, apoptosis, growth and neurotrophic factor synthesis of rat embryonic stem cells (RESCs) cultured in 2D and 3D conditions generated using Cultrex® Basement Membrane Extract (BME) and in poly-(L-lactic acid) (PLLA) electrospun sub-micrometric fibres. It is demonstrated that, in the absence of other instructive stimuli, growth, differentiation and paracrine activity of RESCs are directly affected by the different microenvironment provided by the scaffold. In particular, RESCs grown on an electrospun PLLA scaffolds coated or not with BME have a higher proliferation rate, higher production of bioactive nerve growth factor (NGF) and vascular endothelial growth factor (VEGF) compared to standard 2D conditions, lasting for at least 2 weeks. Due to the high mechanical flexibility of PLLA electrospun scaffolds, the PLLA/stem cell culture system offers an interesting potential for implantable neural repair devices.

Custom-made, selective laser sintering (SLS) blade implants as a non-conventional solution for the prosthetic rehabilitation of extremely atrophied posterior mandible.

The treatment of severely atrophied posterior mandibles with standard-diameter root-form implants may present a challenge. Bone reconstructive surgery represents the treatment of choice; however, it may not be accepted by some patients for economic reasons or due to higher morbidity. Computer-aided design/computer-aided manufacturing (CAD/CAM) technologies have recently opened new frontiers in biomedical applications. Selective laser sintering (SLS) is a CAD/CAM technique that allows the fabrication of complex three-dimensional (3D) structures created by computer-generated image-based design techniques. The aim of this study is to present a protocol for the manufacture and clinical use of custom-made SLS titanium blade implants as a non-conventional therapeutic treatment for the prosthetic rehabilitation of extremely atrophied posterior mandibles. Computed tomography datasets of five patients were transferred to a specific reconstruction software, where a 3D projection of the atrophied mandible was obtained, and custom-made endosseous blade implants were designed. The custom-made implants were fabricated with SLS technique, placed in the extremely atrophied posterior (<4 mm width) mandible, and immediately restored with fixed partial restorations. After 2 years of loading, all implants were in function, showing a good esthetic integration. Blade implants can be fabricated on an individual basis as a custom-designed device. This non-conventional approach may represent an option for restoring the atrophied posterior mandible of elderly patients.

Maxillary sinus augmentation using computer-aided design/computer-aided manufacturing (CAD/CAM) technology.

BACKGROUND: Maxillary sinus augmentation is a common method for increasing bone height for insertion of dental implants. In most cases, the graft is manually cut into a roughly appropriate shape by visual estimation during the operation; accordingly, the shape of the graft depends considerably on the experience of the surgeon. We have developed a computer-aided design/computer-aided manufacturing (CAD/CAM) technique to generate custom-made block grafts for sinus augmentation, and a customized cutting guide to precisely position the lateral wall and facilitate membrane elevation, using cone-beam computed tomography (CBCT). METHODS: Custom-made blocks of hydroxyapatite (HA) were preoperatively cut to the required shape, based on a three-dimensional (3D) simulation, using CAD/CAM technology. The custom-made HA blocks were used for sinus augmentation. RESULTS: Five patients underwent bilateral sinus elevation with custom-made HA blocks. Six months later, implants were placed. Two years after placement, all implants were in function. No clinical or prosthetic complications were encountered. CONCLUSIONS: We present a CAD/CAM technique for the fabrication of custom-made block grafts for sinus augmentation.

A novel root analogue dental implant using CT scan and CAD/CAM: selective laser melting technology.

Direct laser metal forming (DLMF) is a new technique which allows solids with complex geometry to be produced by annealing metal powder microparticles in a focused laser beam, according to a computer-generated three-dimensional (3D) model. For dental implants, the fabrication process involves the laser-induced fusion of titanium microparticles, in order to build, layer by layer, the desired object. Modern computed tomography (CT) acquisition and 3D image conversion, combined with the DLMF process, allows the fabrication of custom-made, root-analogue implants (RAI), perfect copies of the radicular units that need replacing. This report demonstrates the successful clinical use of a custom-made, root-analogue DLMF implant. CT images of the residual non-restorable root of a right maxillary premolar were acquired and modified with specific software into a 3D model. From this model, a custom-made, root-analogue, DLMF implant was fabricated. Immediately after tooth extraction, the root-analogue implant was placed in the extraction socket and restored with a single crown. At the 1-year follow-up examination, the custom-made implant showed almost perfect functional and aesthetic integration. The possibility of fabricating custom-made, root-analogue DLMF implants opens new interesting perspectives for immediate placement of dental implants.

P2X2 purinoreceptor protein in hypothalamic neurons associated with the regulation of food intake.

Purines such as ATP act as extracellular messengers through specific purinergic receptors. Three different classes of purinergic receptors have been identified and termed P1, P2X and P2Y. The purinergic receptor subunit P2X2 is a ligand-gated ion channel that is widely expressed by neurons in the central nervous system. The aim of this study was to study the cellular localization and to identify the chemical phenotypes of ionotropic P2X2 receptor (P2X2R)-containing neurons in the rat mediobasal hypothalamus by immunohistochemistry using three different P2X2R antisera, with special reference to neurons that influence food intake and body weight. P2X2R immunoreactivity was mainly observed in cell bodies and neural extensions located in the ventromedial part of the hypothalamic arcuate nucleus, a subregion of the nucleus with a weak blood-brain barrier (BBB). At the subcellular level, P2X2R immunoreactivity was located to the periphery of individual cells, likely representing the plasma membrane. Many P2X2R-immunoreactive cell bodies in the arcuate nucleus contained the orexigenic peptides neuropeptide Y (NPY) and agouti-related protein (AgRP), and the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD). In contrast, P2X2R immunoreactive cell bodies of the arcuate nucles only occasionally contained the anorexigenic peptides α-melanocyte-stimulating hormone (α-MSH) or cocaine- and amphetamine-regulated transcript (CART), or the opioid peptide dynorphin (DYN). There was no evidence for colocalization of P2X2R with somatostatin or neuronal nitric oxide synthase (nNOS) in neurons of the arcuate nucleus. In the parvocellular part of the paraventricular nucleus, P2X2R was demonstrated in some corticotropin-releasing hormone (CRH), thyrotropin-releasing hormone (TRH) and CART-containing neurons. In some cell bodies of the lateral hypothalamic area P2X2R was colocalized with DYN. The presence of P2X2R immunoreactivity in primarily orexigenic NPY/AgRP/GABA-containing neurons of the arcuate nucleus suggests that extracellular ATP has a regulatory action on this neuronal population located in a strategic position of the brain.

Divergent effects of joyful and anxiety-provoking music on endothelial vasoreactivity.

OBJECTIVE: To evaluate the extent to which music may affect endothelial function. In previous research, a link between music and physiologic parameters such as heart rate and blood pressure has been observed. METHODS: Randomized four-phase crossover and counterbalanced trial in ten healthy, nonsmoking volunteers (70% male; mean age, 35.6 years) that included self-selections of music evoking joy or provoking anxiety. Two additional phases included watching video clips to induce laughter and listening to audio tapes to promote relaxation. To minimize emotional desensitization, subjects were asked to refrain from using self-selected tapes and images for at least 2 weeks before the assigned study phase. Endothelial function was assessed by brachial artery flow-mediated dilation (FMD) and measured as percent diameter change after an overnight fast. After baseline FMD measurements, subjects were randomized to a 30-minute phase of the testing stimulus followed by poststudy FMD; they returned a minimum of 1 week later for the subsequent task. A total of 160 FMD measurements were obtained. RESULTS: Compared with baseline, music that evoked joy was associated with increases in mean upper arm FMD (2.7% absolute increase; p < .001), whereas reductions in FMD were observed after listening to music that elicited anxiety (0.6% absolute decrease; p = .005 difference between joyful and anxiety-provoking music). Self-selected joyful music was associated with increased FMD to a magnitude previously observed with aerobic activity or statin therapy. CONCLUSION: Listening to joyful music may be an adjunctive life-style intervention for the promotion of vascular health.

Prospective clinical evaluation of 1920 Morse taper connection implants: results after 4 years of functional loading.

PURPOSE: This study evaluated the survival rate and the clinical, radiographic and prosthetic success of 1920 Morse taper connection implants. MATERIAL AND METHODS: One thousand nine hundred and twenty Morse taper connection implants were inserted in 689 consecutive patients, from January 2003 until December 2006. Implants were clinically and radiographically evaluated at 12, 24, 36 and 48 months after insertion (mean follow-up per implant: 25.42 months). Modified plaque index (mPI), modified sulcus bleeding index, probing depth (PD) and the distance between implant shoulder and first crestal bone-implant contact (DIB) were measured in mm. Success criteria included the absence of suppuration and clinically detectable implant mobility, PD<5 mm, DIB<1.5 mm after 12 months of functional loading and not exceeding 0.2 mm for each following year, the absence of recurrent prosthetic complications at the implant-abutment interface. Prosthetic restorations were fixed partial prostheses (364 units), single crowns (SCs: 307 units), fixed full-arch prostheses (53 units) and overdentures (67 units). RESULTS: The overall cumulative implant survival rate was 97.56% (96.12% in the maxilla and 98.91% in the mandible). The cumulative implant success rate was 96.61% (95.25% in the maxilla and 98.64% in the mandible). Only a few prosthetic complications were reported (0.65% of loosening at implant-abutment interface in SCs). CONCLUSION: The use of Morse taper connection implants represents a successful procedure for the rehabilitation of partially and completely edentulous arches. The absence of an implant-abutment interface (microgap) is associated with minimal crestal bone loss. The high mechanical stability significantly reduces prosthetic complications.

Direct laser metal sintering as a new approach to fabrication of an isoelastic functionally graded material for manufacture of porous titanium dental implants.

OBJECTIVES: This work focuses on a titanium alloy implants incorporating a gradient of porosity, from the inner core to the outer surface, obtained by laser sintering of metal powder. Surface appearance, microstructure, composition, mechanical properties and fractography were evaluated. METHODS: All the specimens were prepared by a selective laser sintering procedure using a Ti-6Al-4V alloy powder with a particle size of 1-10 microm. The morphological and chemical analyses were performed by SEM and energy dispersive X-ray spectroscopy. The flexure strength was determined by a three-point bend test using a universal testing machine. The surface roughness was investigated using a confocal scanning laser microscope. The surface roughness variation was statistically evaluated by use of a Chi square test. A p value of <0.05 was considered statistically significant. RESULTS: The original surface microstructure consisted of roughly spherical particles, diameter range 5-50 microm. After exposure to hydrofluoric acid some of these were removed and the microsphere diameter then ranged from 5.1 microm to 26.8 microm. Following an organic acid treatment, particles were replaced by grooves 14.6-152.5 microm in width and 21.4-102.4 microm depth. The metal core consisted of columnar beta grains with alpha and beta laths within the grains. The alloy was composed of 90.08% Ti, 5.67% Al and 4.25% V. The Young's modulus of the inner core material was 104+/-7.7 GPa; while that of the outer porous material was 77+/-3.5 GPa. The fracture face showed a dimpled appearance typical of ductile fracture. SIGNIFICANCE: In conclusion, laser metal sintering proved to be an efficient means of construction of dental implants with a functionally graded material which is better adapted to the elastic properties of the bone. Such implants should minimize stress shielding effects and improve long-term performance.

A new EGFR inhibitor induces apoptosis in colon cancer cells.

The use of agents targeting EGFR represents a new frontier in colon cancer therapy. Among these, mAbs and EGFR tyrosine kinase inhibitors seemed to be the most promising. However they have demonstrated scarce utility in therapy, the former being effective only at toxic doses, the latter resulting inefficient in colon cancer. This paper presents studies on a new EGFR inhibitor, FR18, a molecule containing the same naphthoquinone core as shikonin, an agent with great anti-tumor potential. In HT29, a human colon carcinoma cell line, flow cytometry, immunoprecipitation, and Western blot analysis, confocal spectral microscopy have demonstrated that FR18 is active at concentrations as low as 10 nM, inhibits EGF binding to EGFR while leaving unperturbed the receptor kinase activity. At concentration ranging from 30 nM to 5 microM, it activates apoptosis. FR18 seems therefore to have possible therapeutic applications in colon cancer.

Removal torque values of titanium implants inserted into bone defects filled with hydroxyapatite: a histologic and histomorphometric analysis in rabbit.

The successful clinical use of implants with microrough titanium surfaces has paved the way for the further development of surface topographies to promote enhanced peri-implant bone apposition during the early stages of bone regeneration. The aim of this study is to determine the torque resistance of the implant-bone interface of plasma sprayed titanium endosseous implants placed in the rabbit tibia in three different situations. Hydroxyapatite (HA) particles with a size ranging from 250 to 450 microm were used in the present study to fill out 6 mm bony defects created in rabbit tibia. Fourteen mature New Zealand white male rabbits, weighing about 2.5 Kg., were used in this study. The test sites were filled with HA and the non-grafted sites were used as control. A total of 28 bone defects (14 without HA and 14 with HA.) were created. Implants with plasma-spray surface were subsequently inserted. Six additional rabbits were used; in these animals no bone defects were created. The implant sites were divided into three groups: 1) implants inserted in the tibia without bone defects; 2) implants inserted in the tibia with bone defects not filled with HA; 3) implants inserted in the tibia with bone defects filled with HA particles. The purpose of this study is to measure reverse-torque in three different situations of clinically similar implant geometry in the articulation of rabbits. The null hypothesis stated that there is a difference in reversal torque between the bone regeneration with HA, native bone and bone defect without bone regeneration. Additionally, comparison between these 6-month data and the 3-month data from a previous study led to the following conclusions: a significant difference exists in the removed torque for the TPS implants in the bone regenerated by HA and native bone; increase in removal torque values was seen for the implant inserted in bone regenerated by HA compared to the implant nated in bone without biomaterials. In conclusion, bone regenerated with biomaterials possesses different mechanical characteristics to native bone.

Physical and chemical aspects of a new porous hydroxyapatite.

The new engineered porous hydroxyapatite (EP-HA) described in this paper seems to be suitable as a bone substitute. Its physico-chemical characteristics and morphology are similar to those of natural bone. Study of its histological behaviour in humans revealed bone formation within and around the porous hydroxyapatite that is markedly resorbed.

Body fat distribution and flow-mediated endothelium-dependent vasodilation in older men.

OBJECTIVE: Recent studies indicate that abdominal fat accumulation, in particular intra-abdominal fat, is related to impaired endothelial function in young healthy volunteers. The aim of this study was to examine whether the distribution of body fat depots is related to impaired endothelial function in older men. METHODS: Cross-sectional sample of 38 older (68+/-1 y) sedentary (VO(2max)=2.4+/-0.1 l/min) men. Flow-mediated endothelial dependent vasodilation (EDD) was assessed in the brachial artery in response to reactive hyperemia using high-resolution ultrasound. Abdominal subcutaneous and visceral fat depots were assessed by computed tomography scan (CT-scan) at the L(4)-L(5) region in the supine position. Percentage body fat was assessed via dual-energy X-ray absorptiometry (DEXA). RESULTS: Flow-mediated percentage change in brachial artery was 7.6+/-0.7%, suggesting an impaired flow-mediated EDD. Using simple linear regression analysis, there were no statistically significant relationship observed between flow-mediated EDD and the indices of total and abdominal adiposity (percentage body fat=29.3+/-0.9%, r=-0.11; total abdominal fat area=465+/-23 cm(2), r=-0.1; intra-abdominal fat area=200+/-14 cm(2), r=-0.14; subcutaneous fat area=265+/-13 cm(2), r=-0.05; BMI=29.3+/-0.9 kg/m(2), r=-0.07; and waist to hip ratio=0.98+/-0.01, r=-0.20). CONCLUSION: These findings suggest that in older sedentary men there is no clear correlation between adiposity and body fat distribution and impairment of flow-mediated endothelium dependent vasodilation.

Single tooth replacement by Morse taper connection implants: a retrospective study of 80 implants.

The goal of this study was to provide data relative to the use of a new implant system (Mac System, Cabon, Milan, Italy) with a Morse taper implant-abutment connection for single implant restorations. The implant system is composed of an endosseous screw made of commercially pure titanium grade 2, while the abutment is titanium alloy (Ti-6Al-4V). A total of 80 single implants were placed in 69 patients (36 women and 33 men, mean age 42 years, range 16 to 61). All patients gave their informed consent and received a thorough clinical and radiographic examination. Smokers and diabetics were excluded from the study. Three implants were placed in areas of previous tooth impaction, 5 were placed in posttraumatic edentulous areas, 2 were used in situations involving tooth agenesis, and 60 replaced teeth lost because of caries or periodontal disease. All patients were edentulous for at least 1 year prior to treatment. The implants received a definitive prosthesis and had been in function for a mean period of 3.5 years. At second-stage surgery, 2 implants were removed because of lack of osseointegration. After 2 years of loading, 1 implant showed evidence of peri-implantitis and was removed. In addition, 2 fractured abutments and 1 loosened abutment were observed. Few mechanical or infectious complications were seen, and this may have been the result of high stability of the conical connection.