Domenico Ciavarella

Biomarkers of Periodontal Tissue Remodeling during Orthodontic Tooth Movement in Mice and Men: Overview and Clinical Relevance

Biologically active substances are expressed by cells within the periodontium in response to mechanical stimuli from orthodontic appliances. Several possible biomarkers representing biological modifications during specific phenomena as simile-inflammatory process, bone resorption and formation, periodontal ligament changes, and vascular and neural responses are proposed. Citations to potentially published trials were conducted by searching PubMed, Cochrane databases, and scientific textbooks. Additionally, hand searching and contact with experts in the area were undertaken to identify potentially relevant published and unpublished studies. Selection criteria were as follows: animal models involving only mice and rats undergoing orthodontic treatment; collection of gingival crevicular fluid (GCF) as a noninvasively procedure for humans; no other simultaneous treatment that could affect experimental orthodontic movement. The data suggest that knowledge of the remodeling process occurring in periodontal tissues during orthodontic and orthopedic therapies may be a clinical usefulness procedure leading to proper choice of mechanical stress to improve and to shorten the period of treatment, avoiding adverse consequences. The relevance for clinicians of evaluating the rate of some substances as valid biomarkers of periodontal effects during orthodontic movement, by means of two models of study, mice and men, is underlined.

Effect of desquamative gingivitis on periodontal status: a pilot study.

OBJECTIVE Desquamative gingivitis (DG) represents the gingival manifestation associated with several mucocutaneous disorders and systemic conditions. Little is known of whether or not DG could influence the onset or progression of plaque-related periodontitis. In this study, the potential impact of DG on plaque-related attachment loss and pocket formation has been evaluated. METHODS A cross-sectional evaluation of 12 patients with DG [eight oral lichen planus (OLP), four mucous membrane pemphigoid (MMP)], never treated for DG lesions or plaque-related periodontitis, was carried out. Probing depth (PD), clinical attachment loss (CAL), full-mouth plaque (FMPS), and bleeding (FMBS) scores were evaluated at six sites per tooth. Clinical parameters of sites with DG lesions were compared with that of DG unaffected sites. RESULTS Median PD and CAL, as well as FMPS and FMBS, were not significantly different (P > 0.05 Mann-Whitney test) for both OLP and MMP patients. However, a negative association between DG lesions and PD < 4 mm (OLP: OR = 0.26; MMP: OR = 0.47), and a positive association with PD 4-6 mm (OLP: OR = 3.76; MMP: OR = 2.68) and with PD > 6 mm (only for OLP: OR = 3.83) were found to be significant. CONCLUSIONS The potential interference between DG lesions and periodontitis needs further prospective investigation; nonetheless, a higher level of attention might be prudent.

Prognostic value analysis of urokinase-type plasminogen activator receptor in oral squamous cell carcinoma: an immunohistochemical study.

BackgroundOral squamous cell carcinoma (OSCC) represents the most common oral malignancy. Despite recent advances in therapy, up to 50% of the cases have relapse and/or metastasis. There is therefore a strong need for the identification of new biological markers able to predict the clinical behaviour of these lesions in order to improve quality of life and overall survival. Among tumour progression biomarkers, already known for their involvement in other neoplasia, a crucial role is ascribed to the urokinase-type plasminogen activator receptor (uPAR), which plays a multiple role in extracellular proteolysis, cell migration and tissue remodelling not only as a receptor for the zymogen pro-uPA but also as a component for cell adhesion and as a chemoattractant. The purpose of this study was to gain information on the expression of uPAR in OSCC and to verify whether this molecule can have a role as a prognostic/predictive marker for this neoplasia.MethodsIn a retrospective study, a cohort of 189 OSCC patients was investigated for uPAR expression and its cellular localization by immunohistochemistry. As standard controls, 8 normal oral mucosal tissues free of malignancy, obtained from patients with no evidence or history of oral cavity tumours, were similarly investigated. After grouping for uPAR expression, OSCCs were statistically analyzed for the variables age, gender, histological grading (G), tumour size, recurrence, TNM staging and overall survival rate.ResultsIn our immunohistochemical study, 74 cases (39.1%) of OSCC showed a mostly cytoplasmic positivity for uPAR, whereas 115 were negative. uPAR expression correlated with tumour differentiation grade and prognosis: percentage of positive cases was the greatest in G3 (70.4%) and patients positives for uPAR expression had an expectation of life lower than those for uPAR negatives.ConclusionThe results obtained in this study suggest a role of uPAR as a potential biomarker useful to identify higher risk subgroups of OSCC patients.

Inhibiting proliferation in KB cancer cells by RNA interference-mediated knockdown of nicotinamide N-methyltransferase expression.

The enzyme Nicotinamide N-methyltransferase (NNMT) catalyzes the methylation of nicotinamide and other pyridines, playing a pivotal role in the biotransformation and detoxification of many drugs and xenobiotic compounds. Several tumours have been associated with abnormal NNMT expression, however its role in tumour development remains largely unknown. In this study we investigated expression levels of Nicotinamide N-methyltransferase in a cancer cell line and we evaluated the effect of shRNA-mediated silencing of NNMT on cell proliferation. Cancer cells were examined for NNMT expression by semiquantitative RT-PCR and Western blot analysis. A HPLC-based catalytic assay was performed to assess enzyme activity. Cells were transfected with four shRNA plasmids against NNMT and control cells were treated with transfection reagent only (mock). The efficiency of gene silencing was detected by Real-Time PCR and Western blot analysis. MTT cell proliferation assay and the soft agar colony formation assay were then applied to investigate the functional changes in cancerous cell. NNMT mRNA was detected in cancer cells, showing a very high expression level. In keeping with the results of RT-PCR analysis, the protein level and NNMT enzyme activity were particularly high in KB cells. ShRNA vectors targeted against NNMT efficiently suppressed gene expression, showing inhibition observed at both the mRNA and protein levels. Down-regulation of NNMT significantly inhibited cell proliferation and decreased colony formation ability on soft agar. The present data support the hypothesis that the enzyme plays a role in tumour expansion and its inhibition could represent a possible molecular approach to the treatment of cancer.

Aging and Oral Health: Effects in Hard and Soft Tissues

Changing demographics, including an increase in life expectancy and the growing numbers of elderly has recently focused attention on the need for geriatric dental care. Ageing affects oral tissues in addition to other parts of the human body, and oral health (including oral mucosa, lips, teeth and associated structures, and their functional activity) is an integral component of general health; indeed, oral disease can cause pain, difficulty in speaking, mastication, swallowing, maintaining a balanced diet, not to mention aesthetical considerations and facial alterations leading to anxiety and depression. The World Health Organization recommends the adoption of certain strategies for improving the oral health of the elderly, including the management and maintenance of oral conditions which are necessary for re-establishing effective masticatory function. Oral health is often neglected in the elderly, and oral diseases associated with aging are complex, adversely affecting the quality of life. Although oral health problems are not usually associated with death, oral cancers result in nearly 8,000 deaths each year, and more than half of these occur at an age of 65 years plus. This report, which is dedicated to geriatric physicians, geriatric dentistry and specialists in oral medicine reviews age-related oral changes in elderly patients and efforts to summarize the effects of aging in hard and soft oral tissues.

β- and γ-catenin expression in oral dysplasia

Cell-cell and cell-matrix interactions regulate important cellular functions; they involve a number of specialised molecules and the corresponding receptors, among which a key role is played by cadherins and the associated catenins. Deregulation of these molecules has been associated with tumour progression in many human malignancies. While catenins expression has been extensively studied in many human cancers, including oral carcinoma (OSCC), less is known about their expression in oral epithelial dysplasia. The objective of this study was to evaluate the expression of these proteins in a large group of displastic lesions of the oral mucosa and their relation with subsequent malignant transformation. Expression of beta- and gamma-catenin was investigated by immunohistochemistry using specific monoclonal antibodies in 49 cases of oral epithelial dysplasia and 10 samples of normal oral mucosa. The presence and absence of beta- and gamma-catenin staining was expressed differently in relation to dysplasia grade; while the degree of dysplasia became more severe, we observed a statistically significant loss and/or reduction of catenins expression, the loss of the exclusive membranous expression and a cytoplasmic delocalisation. Progression to OSCC occurred in 10 out of our 49 cases (20.4%); all of them, except one, showed a concurrent and concordantly located beta- and gamma-catenin staining even, if no statistically significant differences were found between cases progressed to invasive OSCC or not. Catenins physiology alterations may be involved in the transformation process; however, the role of catenins expression as possible prognostic markers in precancerous oral lesions seems to be limited. Nonetheless, further studies on larger series of samples are necessary in order to clarify the role of catenins expression in oral carcinogenesis from both a biological and clinical point of view.

LANGERHANS CELL HISTIOCYTOSIS: ORAL/PERIODONTAL INVOLVEMENT IN ADULT PATIENTS

OBJECTIVE Langerhans cell histiocytosis (LCH) is a clonal proliferative multisystem disease. Although bone and mucosae have been classified as non-risk organs, their involvement may increase the risk of disease progression. Oral and periodontal lesions are burdened with a significant impairment of quality of life for associated signs, symptoms and loss of function. Most of information regards paediatric disease; the disease in adults has received limited attention. SUBJECTS AND METHODS A total of 31 adult patients affected by immuno-histopathology confirmed LCH have been prospectively examined; attention was paid to the occurrence and characterization of oral lesions. RESULTS Twelve patients developed oral lesions. Posterior regions of jawbones were always affected; the involvement of anterior regions was not constant. Unifocal oral involvement was significantly associated with multisystemic disease while multifocal lesions were associated with unisystemic disease. Oral disease presented with soft tissue ulcers (50% of cases), gingival bleeding (66.7%), pain (83.4%), periodontal damage (50%), tooth mobility (16.7%), non-healing extraction socket (8.3%); 41.6% of patients complained of negative outcomes on quality of life. Oral lesions were easily handled with local measures. CONCLUSIONS Posterior regions require attention; single oral lesions may be part of multisystemic disease; oral and periodontal lesions may be early signs of disease reactivation.

Changes in pharyngeal aerobic microflora in oral breathers after palatal rapid expansion

BackgroundThe purpose of this study was to investigate in oral breathing children the qualitative and quantitative effects on aerobic and facultatively anaerobic oropharyngeal microflora of respiratory function improved by rapid palatal expansion (RPE).MethodsIn an open clinical trial, we studied 50 oral breathers, aged 8 to 14 years and suffering from both maxillary constriction and posterior cross-bite. At baseline, patients were examined by a single otorhinolaryngologist (ENT), confirming nasal obstruction in all subjects by posterior rhino-manometric test. Patients were evaluated three times by oropharyngeal swabs:1) at baseline (T = 0); 2) after palatal spreading out (T = 1); and 3) at the end of RPE treatment (T = 2). With regard to the microbiological aspect, the most common and potentially pathogenic oral microrganisms (i.e. Streptococcus pyogenes, Diplococcus pneumoniae, Staphylococcus aureus, Haemophilus spp, Branhamella catarrhalis, Klebsiella pneumoniae, Candida albicans) were specifically detected in proper culture plates, isolated colonies were identified by means of biochemical tests and counted by calibrated loop. The data were analyzed by means of the following tests: Chi-square test, Fishers exact test and Wilcoxons test.ResultsAfter the use of RME there was a statistically significant decrease of Staphylococcus aureus stock at CFU/mLat T1(P = 0.0005; Z = -3,455 by Wilcoxon Rank test) and T2 (P < 0.0001; Z = -4,512 by Wilcoxon Rank test) vs T0. No significant changes were found for the other examined microrganisms.ConclusionOur data suggest that RPE therapy in oral breathers may strongly reduce the pathogenic aerobic and facultatively anaerobic microflora in the oral pharynx after a normalization of the upper airways function, and may reduce the risk of respiratory infections.

Immediate placement and temporization of implants: three- to five-year retrospective results.

The immediate placement of dental implants in esthetic areas is a primary challenge for modern implantology. The underlying treatment goal is to preserve the natural periodontal architecture; in recent years, however, a concurrent goal has been to reduce the period between implant placement in the fresh extraction socket and delivery of the definitive restoration, but adequate long-term data are still lacking on the efficacy of this technique. A 3- to 5-year retrospective analysis of 282 dental implants immediately placed into extraction sockets, and temporized with nonoccluding provisional prostheses has been undertaken. All recorded outcomes and complications, as well as a proposed protocol for management of immediate function, are discussed.

Condylar Position Indicator and T-Scan system II in clinical evaluation of temporomandibular intracapsular disease

INTRODUCTION The pathogenesis of temporomandibular joint intracapsular disease (TMJI) is multifactorial and its diagnosis is not easy. In this work authors show two types of clinical analysis: the Condylar Position Indicator (CPI) and T-Scan 2 system. MATERIAL AND METHODS Twenty patients (mean age of 24.5 years) with TMJI problem and 10 healthy matched subjects (mean age: 25.4 years) were selected. Analysis of TMJI was performed on each patient by means of Condylar Position Indicator (CPI) and T-Scan System II tests. RESULTS Eight patients presented vertical symmetrical condylar distraction greater than healthy subjects (P-value<0.001). T-Scan showed a difference of Percentage of Force (POF) not greater than 5%. Seven patients showed sagittal shift greater than healthy subject (P-value<0.001). T-Scan records showed a difference of POF greater than 5%. Five non-healthy subjects presented sagittal, vertical, transverse shift greater than healthy subjects (P-value<0.001). T-Scan records show a difference of POF greater than 5%. CONCLUSION In this work authors present a new method of analysis. CPI indicates discrepancy of the condyle position in CO from CR and T-Scan allows the operator to study all teeth contacts and occlusal forces taking place during dynamic jaw movement.