Mario Aimetti

MET receptor is overexpressed but not mutated in oral squamous cell carcinomas.

Oral squamous cell carcinoma (SCC) is a neoplasm characterized by a high degree of local invasion and an elevated rate of metastasis to cervical lymph nodes. It has been shown that the Hepatocyte Growth Factor/Scatter Factor Receptor Met is constitutively activated in many human tumors of epithelial origin and that it plays a critical role to confer invasive properties to neoplastic cells. Most frequently, Met activation is due to receptor overexpression, but also point mutations in the tyrosine kinase domain can lead to deregulated activation. Here we show that in all the primary tumors examined this receptor is overexpressed. Direct sequencing of Met mRNAs failed to find any activating mutation in its intracellular domain. Moreover, in cell lines derived from squamous cell carcinomas, HGF‐induced activation of Met resulted in the acquisition of invasive properties. All together these data suggest that the MET oncogene is involved in progression of squamous cell carcinoma toward an invasive‐metastatic behavior.

Full-mouth disinfection and systemic antimicrobial therapy in generalized aggressive periodontitis: a randomized, placebo-controlled trial.

AIM The present investigation aimed to analyse clinical and microbiological effects of systemic administration of metronidazole and amoxicillin combined with the One-Stage-Full-Mouth-Disinfection protocol (OSFMD) in generalized aggressive periodontitis patients (G-AgP). MATERIALS AND METHODS Thirty-nine systemically healthy patients with G-AgP were consecutively included. The test group (n = 19) received amoxicillin-metronidazole combination (500 mg of each, three times a day for 7 days) and the OSFMD, the control group (n = 20) received the OSFMD and a placebo. In addition to clinical parameters subgingival plaque samples from moderate (4-5 mm) and deep (≥ 6 mm) pocket sites were analysed for the presence of Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola using polymerase chain reaction. RESULTS Both therapies led to a statistically significant decrease in clinical and microbiological parameters compared to baseline (p < 0.001). The most beneficial changes were observed in the test group which showed significantly greater improvements in probing depth and clinical attachment level and a lower prevalence of Aggregatibacter actinomycetemcomitans, Treponema denticola, and Tannerella forsythia compared to the control one (p < 0.05). CONCLUSIONS Systemic administration of metronidazole and amoxicillin as an adjunct to OSFMD therapy significantly improved clinical and microbiological outcomes in patients with G-AgP over a 6-month period.

Association among oral health, apical periodontitis, CD14 polymorphisms, and coronary heart disease in middle-aged adults.

INTRODUCTION There is evidence to suggest that an association exists between oral infections and coronary heart disease (CHD). Subjects presenting lesions of endodontic origin (LEOs) or pulpal inflammation had an increased risk of developing CHD. However, findings concerning systemic manifestations of apical periodontitis (AP) remain controversial. An association between CD14 gene polymorphisms and atherosclerosis-associated diseases has been shown, but there are no data regarding an association between CD14 polymorphism and AP. This study evaluated associations between clinical oral health status, CD14 polymorphisms, and CHD. METHODS A case-controlled clinical trial was designed to compare middle-aged adults with acute myocardial infarction or unstable angina (n = 51) within 12 months of the acute event defined as first manifestation with healthy controls (n = 49). Participants were matched for age, sex, and socioeconomic status. Indicators of oral disease and compliance were evaluated. CD14 polymorphisms were analyzed by restriction fragment length polymorphism-polymerase chain reaction. RESULTS CHD subjects had a higher prevalence of oral diseases and lower compliance to oral preventive strategies than healthy controls. Multivariate analysis showed a positive association between missing teeth (odds ratio [OR] = 1.37; 95% confidence interval [CI], 1.02-1.85), the number of LEOs (OR = 4.37; 95% CI, 1.69-11.28), chronic periodontitis (OR = 5.87; 95% CI, 1.17-29.4), and CHD. No statistically significant association emerged between the CD14 C(-260)T and the CD14 C(-159)T polymorphism, endodontic or periodontal disease, and CHD. CONCLUSIONS Chronic oral diseases may increase the risk of CHD and may be an unconventional risk factor for CHD.

Bone production by human maxillary sinus mucosa cells

The Schneider membrane is the mucosa that covers the inner part of the maxillary sinus cavities. The free surface is a ciliated pseudostratified epithelium, while the deeper portion is a highly vascularized connective tissue. The stromal fraction, bordering the bony wall of the sinus, after tooth loss can exhibit increased osteoclastic activity resulting in resorption of the bone in the posterior maxilla. Goal of our study was to isolate and characterize mesenchymal progenitors in the Schneiders membrane connective net and to evaluate their self ability to differentiate toward osteoblastic lineage, in absence of osteoinductive factors and osteoconductive biomaterials of support. This should indicate that maxillary sinus membrane represents an useful an approachable source of MSCs for bone tissue engineering and cell therapy and owns the intrinsic capacity to restore maxillary bone after tooth loss without the needing of biomaterials. J. Cell. Physiol. 227: 3278–3281, 2012.

One-Stage Full-Mouth Disinfection as a Therapeutic Approach for Generalized Aggressive Periodontitis

BACKGROUND Data concerning treatment outcomes in patients with generalized aggressive periodontitis (GAgP) are limited. The aim of this study is to investigate 6-month clinical and microbiologic outcomes of the one-stage full-mouth disinfection (OSFMD) in the management of patients with GAgP. METHODS Twenty-seven patients with advanced GAgP were included in this prospective follow-up intervention study. Clinical and microbiologic parameters were collected at baseline and 3 and 6 months after the OSFMD. Patient-, tooth-, and site-level analyses were carried out. Subgingival samples from moderate (4 to 5 mm) and deep (≥6 mm) pocket sites were analyzed using a polymerase chain reaction for Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans), Prevotella intermedia, Porphyromonas gingivalis, Tannerella forsythia (previously T. forsythensis), and Treponema denticola. RESULTS The OSFMD resulted in significant improvements in all parameters. After 6 months, the whole-mouth probing depth (PD) decreased from 4.2 ± 1.1 mm to 2.8 ± 0.6 mm, and the clinical attachment level was reduced from 4.5 ± 1.2 mm to 3.4 ± 1.1 mm (P <0.001). When data were analyzed based on the frequency distribution of PD, the number of sites with PD ≥5 mm decreased by 61% from baseline values, and mean PD reductions of 1.5 and 2.5 mm were noted in moderate and deep pockets, respectively. At 6 months, percentages of moderate and deep sites free of pathogens were 40% and 27%, respectively. CONCLUSION The OSFMD may be a viable approach to deal with severe GAgP.

Osteogenic Potential of Human Oral‐Periosteal Cells (PCs) Isolated From Different Oral Origin: An In Vitro Study

The periosteum is a specialized connective tissue containing multipotent stem cells capable of bone formation. In this study, we aimed at demonstrating that human oral periosteal cells derived from three different oral sites (upper vestibule, lower vestibule, and hard palate) represent an innovative cell source for maxillo‐facial tissue engineering applications in terms of accessibility and self‐commitment towards osteogenic lineage. Periosteal cells (PCs) were isolated from patients with different ages (20–30 yy, 40–50 yy, 50–60 yy); we then analyzed the in vitro proliferation capacity and the bone self‐commitment of cell clones culturing them without any osteogenic supplement to support their differentiation. We found that oral PCs, independently of their origin and age of patients, are mesenchymal stem cells with stem cell characteristics (clonogenical and proliferative activity) and that, even in absence of any osteogenic induction, they undertake the osteoblast lineage after 45 days of culture. These results suggest that oral periosteal cells could replace mesenchymal cells from bone marrow in oral tissue‐engineering applications. J. Cell. Physiol. 231: 607–612, 2016.

Soft tissue and crestal bone changes around implants with platform-switched abutments placed nonsubmerged at subcrestal position: a 2-year clinical and radiographic evaluation.

PURPOSE To evaluate crestal bone changes around implants with platform-switched abutments placed 1 mm subcrestally in a prospective clinical investigation. MATERIALS AND METHODS Forty consecutive systemically healthy patients (mean age ± standard deviation [SD], 55.2 ± 8.7 years) with one or more missing teeth were consecutively treated with 1-mm subcrestally positioned, platform-switched, tapered, full treated implants restored with coded abutments. A total of 58 implants were placed. Final restorations were delivered 4 to 8 months after implant insertion. Digital standardized periapical radiographs using customized film holders were obtained at the time of implant insertion, and at 12 and 24 months after final prosthesis placement. Marginal peri-implant bone levels were measured at the mesial and distal surfaces of each implant using digital image software. RESULTS All implants osseointegrated and were clinically stable at the 2-year follow-up. The cumulative survival rate was 100%. From implant insertion to the 2-year follow-up, the mean bone loss was 0.32 ± 0.37 mm. No significant differences related to sex, implant site, and bone density were observed. The mean midbuccal and interproximal soft tissue margin positions were 1.13 ± 0.5 mm and 1.15 ± 0.6 mm coronal to the prosthetic finish line, respectively. CONCLUSION There is limited clinical information regarding the amount of marginal bone loss around two-piece platform-switched implants placed at subcrestal positions. Results of this study suggest that platform switching and subcrestal location of the implant-abutment interface may be effective in reducing bone loss and in preserving esthetics around dental implants.

Merkel Cells and Permanent Disesthesia in the Oral Mucosa After Soft Tissue Grafts

Connective tissue grafts are routinely procedures in the treatment of gingival defects. The clinical success of the gingival tissue graft procedures anyway should ensure not only the aesthetic integration between the tissues but also the physiological activity of the graft in terms of sensitivity and immunity because the skin and the mucosae constitute the first natural aspecific borders against pathogens. The aim of this paper was to investigate nervous net recovery after connective graft procedure, in relation with sensorial alteration in the injured area. Results showed that there is a close link among the number of Merkel cells and the alteration of sensations. Merkel cells can be found isolated standing in the basal layer, supposed to have neuroendocrine functions in the epithelia or in larger group not associated with nerves; when found in association with nerves they are named Merkel complexes, acting as slow adapter mechanical receptor. Our data can be explained in two ways: Merkel cells increase as a consequence of tissue injury, a sort of “SOS cells” that secrete neuroendocrine signals to guide tissue healing; as an alternative the presence of the Merkel cells could be read as a derailment of tissue regeneration with the stop of cellular differentiation in the direction of an abnormal proliferation, a sort of mad stem cell. J. Cell. Physiol. 224:205–209, 2010

A novel image processing technique for three-dimensional volumetric analysis of severely resorbed alveolar sockets with cone beam computed tomography

BACKGROUND The aim of this study was to present and validate a novel procedure for the quantitative volumetric assessment of extraction sockets that combines cone-beam computed tomography (CBCT) and image processing techniques. METHODS The CBCT dataset of 9 severely resorbed extraction sockets was analyzed by means of two image processing software, Image J and Mimics, using manual and automated segmentation techniques. They were also applied on 5-mm spherical aluminum markers of known volume and on a polyvinyl chloride model of one alveolar socket scanned with Micro-CT to test the accuracy. RESULTS Statistical differences in alveolar socket volume were found between the different methods of volumetric analysis (P<0.0001). The automated segmentation using Mimics was the most reliable and accurate method with a relative error of 1.5%, considerably smaller than the error of 7% and of 10% introduced by the manual method using Mimics and by the automated method using ImageJ. CONCLUSIONS The currently proposed automated segmentation protocol for the three-dimensional rendering of alveolar sockets showed more accurate results, excellent inter-observer similarity and increased user friendliness. The clinical application of this method enables a three-dimensional evaluation of extraction socket healing after the reconstructive procedures and during the follow-up visits.

Osseous resective surgery with and without fibre retention technique in the treatment of shallow intrabony defects: a split‐mouth randomized clinical trial

AIM The aim of this split-mouth clinical trial was to compare the effectiveness of Apically Positioned Flap with Fibre Retention Osseous Resective Surgery (FibReORS) or Osseous Resective Surgery (ORS) in the treatment of periodontal pockets associated with intrabony defects ≤ 3 mm at posterior natural teeth. MATERIALS AND METHODS Twenty-six posterior sextants requiring osseous resective surgery were selected in 13 chronic periodontitis patients: 13 sextants were randomly assigned to ORS and 13 to FibReORS. Clinical evaluation of probing depth (PD), gingival recession and clinical attachment level was performed at baseline, 6 and 12 months postoperatively. Periapical radiographs were taken prior and after surgical treatment, at 6- and 12-month follow-up. RESULTS Ostectomy amounted to 1.0 ± 0.3 mm in the ORS group and to 0.4 ± 0.2 mm in the FibReORS group. At 12-month examination PD changes did not significantly differ between the experimental groups. ORS group showed significantly (p < 0.001) greater clinical attachment loss (2.2 ± 1.0 mm versus 1.0 ± 0.6 mm), radiographic bone resorption (0.43 ± 0.08 mm versus 0.13 ± 0.09 mm) and post-operative patient discomfort compared to FibReORS. CONCLUSION FibReORS resulted in similar PD reduction, but less ostectomy, clinical attachment loss and patient morbidity compared to ORS.