Molecular evaluation of tissue proteins in vivo during controlled orthodontic movement.

Orthodontic tooth movement determines a biological response of all the tissues surrounding the teeth to which force is applied. The aim of this study is to evaluate which ideal orthodontic force, at the biological level, arouses an acute inflammatory response on periodontal tissues, and the duration of the force in order to establish an ideal experimental model of dental movement. The periodontal ligament and the alveolar bone change abruptly due to the biochemical adaptive response, resulting in a re-organization of the intracellular and the extracellular matrix. There is a modification of the local vascularization which stimulates a cascade production, synthesis and the release of arachidonic acid, metabolites, proteins, such as cytokines, and growth factors. Every dentist can control and should know the above-mentioned mechanism. Moreover, the production of proteins by modulating the direction and the intensity of the force can be changed but, above all, the duration.

Functional and molecular outcomes of the human masticatory muscles.

The masticatory muscles achieve a broad range of different activities such as chewing, sucking, swallowing, and speech. In order to accomplish these duties, masticatory muscles have a unique and heterogeneous structure and fiber composition, enabling them to produce their strength and contraction speed largely dependent on their motor units and myosin proteins that can change in response to genetic and environmental factors. Human masticatory muscles express unique myosin isoforms, including a combination of thick fibers, expressing myosin light chains (MyLC) and myosin class I and II heavy chains (MyHC) -IIA, -IIX, α-cardiac, embryonic and neonatal and thin fibers, respectively. In this review, we discuss the current knowledge regarding the importance of fiber-type diversity in masticatory muscles versus supra- and infrahyoid muscles, and versus limb and trunk muscles. We also highlight new information regarding the adaptive response and specific genetic variations of muscle fibers on the functional significance of the masticatory muscles, which influences craniofacial characteristics, malocclusions, or asymmetry. These findings may offer future possibilities for the prevention of craniofacial growth disturbances.

Immunometabolic biomarkers of inflammation in Behçet's disease: relationship with epidemiological profile, disease activity and therapeutic regimens.

Behcet's disease (BD) is a systemic inflammatory disease with a still unclear pathogenesis. Although several inflammatory molecules have been studied, current biomarkers are largely insensitive in BD and unable to predict disease progression and response to treatment. Our primary aim was to explore serum levels of soluble CD40 L (sCD40L), soluble intracellular adhesion molecule (sICAM-1), monocyte chemoattractant protein-1 (MCP-1), myeloperoxidase (MPO), leptin, resistin, osteoprotegerin (OPG), soluble type 1 tumour necrosis factor receptor (sTNFR), interleukin (IL)-6 and serum amyloid A (SAA) serum concentration in a cohort of 27 BD patients. The secondary aim was to evaluate potential correlations between the putative circulating biomarkers, demographic profile of patients, the status of disease activity, the specific organ involvement at the time of sample collection and different therapeutic regimens. Serum concentrations of sTNFR (P = 0·008), leptin (P = 0·0011), sCD40L (P < 0·0001) and IL-6 (P = 0·0154) were significantly higher in BD patients than in HC, while no difference was found in MCP-1, MPO and resistin serum levels. Moreover, we observed significantly higher sTNFR serum concentrations in BD patients presenting inactive disease than HC (P = 0·0108). A correlation between sTNFR and age was also found, with higher levels in patients over 40 years than HC (P = 0·0329). Although further research is warranted to elucidate the role of circulating biomarkers, some of that may contribute to the understanding of the physiopathology processes underlying BD activity and damage as well as to provide useful tools for prognostic purposes and a personalized treatment approach.

Oscillatory mTOR inhibition and Treg increase in kidney transplantation.

Intracellular metabolic pathways dependent upon the mammalian target of rapamycin (mTOR) play a key role in immune-tolerance control. In this study, we focused on long-term mTOR-dependent immune-modulating effects in kidney transplant recipients undergoing conversion from calcineurin inhibitors (CNI) to mTOR inhibitors (everolimus) in a 1-year follow-up. The conversion to everolimus is associated with a decrease of neutrophils and of CD8(+) T cells. In addition, we observed a reduced production of interferon (IFN)-γ by CD8(+) T cells and of interleukin (IL)-17 by CD4(+) T lymphocytes. An increase in CD4(+) CD25(+) forkhead box protein 3 (FoxP3)(+) [regulatory T cell [(Treg)] numbers was also seen. Treg increase correlated with a higher proliferation rate of this regulatory subpopulation when compared with the CD4(+) FoxP3(-) effector counterpart. Basal phosphorylation level of S6 kinase, a major mTOR-dependent molecular target, was substantially maintained in patients treated with everolimus. Moreover, oscillations in serum concentration of everolimus were associated with changes in basal and activation-dependent S6 kinase phosphorylation of CD4(+) and CD8(+) T cells. Indeed, T cell receptor (TCR) triggering was observed to induce significantly higher S6 kinase phosphorylation in the presence of lower everolimus serum concentrations. These results unveil the complex mTOR-dependent immune-metabolic network leading to long-term immune-modulation and might have relevance for novel therapeutic settings in kidney transplants.

Unilateral condylar hyperplasia: diagnosis, clinical aspects and operative treatment. A case report.

BACKGROUND: Condylar hyperplasia of the mandible is an uncommon idiopathic disorder of the jaw characterised by increased volume of the condyle, unilaterally or bilaterally, leading to facial asymmetry, mandibular deviation, malocclusion and articular dysfunction. CASE REPORT: The authors present one case of unilateral condylar hyperplasia of a 16-year-old patient affected by severe facial asymmetry. Conventional X-rays examinations, multislice spiral CT and bone SPECT were used for the final diagnosis of primary condyle hyperplasia. The patient was treated with a combined orthodontic and surgical approach. CONCLUSION: Treatment of condylar hyperplasia with a combined orthodontic and surgical approach including condylectomy yield good aesthetic and functional outcomes.

Anticoagulant therapy in patients undergoing dental interventions: a critical review of the literature and current perspectives.

Patients treated with oral anticoagulant therapy (OAT) represent an issue to the dentist, as an increasing number of people are using anticoagulant drugs for cardiovascular disease. The choice of an eventual suspension or continuation of anticoagulant therapy is important when considering an efficient management of the patient. Patients in anticoagulant therapy and requiring dental procedures sometimes represent therapeutic concerns especially concerning the suspension of the anticoagulant treatment. At the moment there is no consensus among international experts of a possible discontinuation of therapy before invasive dental procedures. In this paper, the authors try to focus on this topic through a critical review of the literature. Most of the studies suggest the continuation of the anticoagulant treatment with heparin before invasive oral surgical interventions. Based on the data of the literature, two rules must be adopted in clinical practice: 1) maintenance of anticoagulation related to the international normalized ratio (INR); 2) local application of antifibrinolytic agents to ensure a proper hemostatic process. Given the widespread use of anticoagulant drugs in cardiovascular disease, dentists must often face the problem of the therapy and, since there is no consensus on the management of these patients, the authors propose, after a thorough critical review of the literature, the implementation of a multiphase protocol of surgical approach to be implemented with safety in daily clinical practice.

Differential expression of transglutaminase genes in patients with chronic periodontitis.

OBJECTIVE: Gingival epithelium plays a key role in the protection of oral tissues from microbial challenge, especially during the periodontal disease. This study was aimed to evaluate levels of mRNA transcripts of different forms of transglutaminase in the human gingival tissues from patients with chronic periodontitis and relative controls. SUBJECTS AND METHODS: This study included 22 patients with chronic periodontitis (CP) and 22 healthy controls. For each patient, the values of probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP) were recorded. Gene expression of transglutaminase 1, transglutaminase 2, transglutaminase 3, and metalloprotease 2 was evaluated by real-time PCR, while that of Factor XIIIA and metalloprotease 9 by RT-PCR. RESULTS: The values of all the clinical parameters were significantly higher in the CP group than in the healthy control group (P < 0.05). In the CP group, the mRNA expression of transglutaminase 1 and transglutaminase 3 was significantly decreased in comparison with healthy control group. A slight nonsignificant changes of transglutaminase 2 gene expression were observed in samples from CP patients in comparison with controls. CONCLUSIONS: These observations suggest that transglutaminase gene expression may be modified in response to chronic injury in the damaged gingival and emphasizes the key role of these enzymes in gingival remodelling/healing and adaptive processes.

Efficacy of orthopedic treatment with protraction facemask on skeletal Class III malocclusion: a systematic review and meta-analysis.

The objective of this systematic review was to estimate the efficacy of protraction facemask on the correction of Class III malocclusion in the short term. A systematic review of articles was performed using different electronic databases (PubMed, Ovid, Cochrane Central Register of Controlled Trials, Web of Science, LILACS, and Google Scholar). Search terms comprised 'orthopedic treatment' and 'Class III malocclusion'. The selection criteria were set in order to include in this review only randomized clinical trials (RCTs) performed treating with facemask Class III growing patients. Studies' selection, data extraction, and risk of bias's assessment were executed independently by two authors using pre-defined data forms. All pooled analyses of data were based on random effects models. A pre-specified subgroup analysis was planned to evaluate the effect of preliminary rapid palatal expansion on facemask efficacy. Three RCTs met our inclusion criteria. In total, data from 155 patients (92 treated and 63 controls) were collected. The treated group showed the following significant changes: ANB° +3.66° [95%CI (2.58, 4.74)]; SNA° +2.10 [95%CI (1.14, 3.06)]; SNB° -1.54 [95%CI (-2.13, -0.95)]; SN-palatal plane -0.82° [95%CI (-1.62, -0.02)]; and SN-mandibular plane +1.51 [95%CI (0.61, 2.41)]. Heterogeneity varied from low to moderate (mean I(2) value: 41.4 ± 20.8). Facemask is effective correcting Class III malocclusion in the short term. The skeletal modifications induced by facemask are forward displacement of maxilla, backward displacement of mandible, clockwise rotation of the mandibular plane, and counterclockwise rotation of the maxillary plane.

Temporomandibular joint involvement in a cohort of patients with Juvenile Idiopatic Arthritis and evaluation of the effect induced by functional orthodontic appliance: clinical and radiographic investigation.

AIM: The aim of the study was to assess possible correlations between the clinical parameters of temporomandibular joint (TMJ) arthritis and pathologic MRI findings of the TMJ in patients affected by juvenile idiopathic arthritis (JIA), and the effect of a functional orthodontic therapy on the evolution of TMJ disorders. MATERIALS AND METHODS: A prospective clinical and nuclear magnetic resonance (NMR) investigation was conducted on a sample of 53 patients (41 female, 12 male) with JIA, treated for 24 months with an Andresen appliance. The involvement of TMJ was defined by clinical and radiological signs. NMR assessments were performed in closed and maximum opening mouth position before (T0) and at the end of functional orthodontic therapy (T1). RESULTS: Fifteen patients showed physical and radiologic TMJ abnormalities. Changes were not uniformly distributed among the different JIA subtypes. Patients with poliarticular JIA (≥5 peripheral joints affected) showed more destructive bony changes. No correlation existed between clinical symptoms and NMR alterations. Approximately one half of the patients experienced significant improvement of the TMJ and muscular pain using the Andresen appliance. CONCLUSION: The prevalence of TMJ involvement in patients suffering of JIA, and the improvement of TMJ and muscular pain associated with the use of functional appliance found in the present study, suggest an alert for TMJ dysfunction in patients with JIA and demonstrate the utility of functional orthodontic therapy in preventing the morbidities associated with TMJ arthritis in JIA.

Dento-skeletal effects of mixed palatal expansion evaluated by postero-anterior cephalometric analysis.

AIM: The aim of this study was to evaluate the dento-skeletal effects of mixed palatal expansion (MPE) on growing patients with a uni- or bilateral posterior crossbite and mild-to-moderate crowding as compared to untreated growing individuals using postero- anterior (PA) cephalometric analysis. MATERIALS AND METHODS: A group of 24 patients (18 girls and 6 boys) treated with a Hyrax- type device was compared to an untreated matched control group at T0 (8.6 yrs ± 2.01) and T1 (10 yrs ± 2.00) using PA cephalograms. The cephalometric analysis included eight bilateral skeletal and dental landmarks. The groups were compared using independent sample t-test to estimate dento-skeletal effects on PA cephalograms. RESULTS: The treated group showed significant changes for the maxillary width (P<0.001) and upper molar width (P<0.001) when compared to those of the control group. CONCLUSION: MPE may effectively increase transverse dimensions and correct posterior crossbites.

Differences in craniofacial characteristics in Southern Italian children from Naples: a retrospective study by cephalometric analysis.

AIM: The present cross-sectional survey was performed to determine cephalometric standards in a large sample (n. 1071) of children from Southern Italy (Naples). MATERIALS AND METHODS: 1071 lateral cephalograms of healthy children, between 8 to 12 years, with various types of occlusion, all with no history of orthodontic treatment before cephalometric analysis were examined. Seven angular and three linear length measurements (SNA, SNB, ANB, SN^GoMe, PN^Pal I^SN, i^GoMe), and three ratios were included. Descriptive statistics, including the mean, standard deviation, and maximum and minimum, values was computed for each cephalometric variable. RESULTS: Changes in angular and linear parameters during the observation period occurred mostly between the ages of 10 and 12 years. The three ratios varied from age and were not characterised by a progressive rise in mean values. Se-N/Go-Pg was greater in 11-year-old boys (p <0.05) and 12-year-old boys (p <0.01); the cranio-maxillary index Se-N/PNS-A1 was greater in 9-year-old girls (p <0.05), whereas the maxilla-mandibular index PNS-A1/Go-Pg was greater in 9-year-old boys (p <0.01). CONCLUSION: The findings provided useful reference cephalometric normative measures for the 8-to-12-year-old Southern Italian children population. Significant differences between boys and girls in the length of the anterior cranial base and ratio were reported.

Transverse changes determined by rapid and slow maxillary expansion--a low-dose CT-based randomized controlled trial.

OBJECTIVES: To compare transverse skeletal changes produced by rapid (RME) and slow (SME) maxillary expansion using low-dose computed tomography. The null hypothesis was that SME and RME are equally effective in producing skeletal maxillary expansion in patients with posterior crossbite. SETTING AND SAMPLE POPULATION: This study was carried out at the Department of Oral Sciences, University of Naples Federico II, Italy. Twelve patients (seven males, five females, mean age ± SD: 10.3 ± 2.5 years) were allocated to the SME group and 14 patients (six males, eight females, mean age ± SD: 9.7 ± 1.5 years) to the RME group. MATERIALS AND METHODS: All patients received a two-band palatal expander and were randomly allocated to either RME or SME. Low-dose computed tomography was used to identify skeletal and dental landmarks and to measure transverse maxillary changes with treatment. RESULTS: A significant increase in skeletal transverse diameters was found in both SME and RME groups (anterior expansion = 2.2 ± 1.4 mm, posterior expansion = 2.2 ± 0.9 mm, pterygoid expansion = 0.9 ± 0.8 mm). No significant differences were found between groups at anterior (SME = 1.9 ± 1.3 mm; RME = 2.5 ± 1.5 mm) or posterior (SME = 1.9 ± 1.0 mm; RME = 2.4 ± 0.9 mm) locations, while a statistically significant difference was measured at the pterygoid processes (SME = 0.6 ± 0.6 mm; RME = 1.2 ± 0.9 mm, p = 0.04), which was not clinically relevant. CONCLUSION: Rapid maxillary expansion is not more effective than SME in expanding the maxilla in patients with posterior crossbite.

A proportional correlation index for space analysis in mixed dentition derived from an Italian population sample.

AIM: The aim of this study was to establish a specific proportional correlation method for space analysis in mixed dentition applicable to the Italian population. MATERIALS AND METHODS: A retrospective analysis was performed on 300 plaster models taken from Italian subjects, 156 females and 144 males, aged between 12 and 25 years, visited at the Department of Orthodontic and Paediatric Dentistry of the University of Messina. RESULTS: The variance analysis (ANOVA) showed a high correlation between the dimension of the mesio-distal diameters of the four mandibular incisor and those of the upper canine and premolars. The correlation coefficient showed the existence of a directly proportional, positive intra- dependence between the two groups. DISCUSSION: The correlation tables used in the present study appear to be much more accurate if applied to groups of patients with similar ethnic backgrounds, thus explaining the differences between the various prediction indexes found in previous publications. CONCLUSION: This study highlights the need to develop specific values to fit the features of the different ethnic groups.

Class II malocclusion division 1: a new classification method by cephalometric analysis.

AIM: The purpose of this study was to analyse the craniofacial and dentofacial skeletal characteristics in untreated subjects with Class II, division 1 malocclusion by mandibular retrusion and to identify different types and their prevalence. MATERIALS AND METHODS: In 152 subjects with Class II, division 1 malocclusion by mandibular retrusion, the differences were determined by lateral cephalograms analysis of variance and chi-square test, respectively. P<0.05 was considered significant. Seven types of mandibular retrusion were identified: three pure, dimensional, rotational and positional, and four mixed. RESULTS: All patients showed significant inter-group differences with P between 0.005 and 0.001. The dimensional type was the most common (28.9%) and the rotational-positional type was the rarest (5.9%). The pure dimensional type had the shortest mandibular body; the pure rotational type had larger SN/GoMe and the lowest AOBO; the pure positional type presented the flattest cranial base, high AOBO. In the mixed types, dento-skeletal features changed depending on how the main types assorted. CONCLUSIONS: Identifying the type of mandibular retrusion is important for differential diagnosis in clinical practice and research.

Incidence and distribution of deciduous molar ankylosis, a longitudinal study.

AIM: To study incidence and distribution of deciduous molar ankylosis. MATERIALS AND METHODS: study design: longitudinal retrospective study. A total of 512 consecutive subjects (aged 5 to 15 years) were examined at the Orthodontics and Paediatric Dentistry Department of the Genoa University School of Dentistry; for each subject an ortopantomography x-ray was taken. RESULTS: Thirty-four children were affected by deciduous molars ankylosis (6.6%). A statistically significant difference was revealed between the distributions: the lower deciduous molars were ankylosed more frequently than the upper ones (P < 0.001); the second deciduous molars were ankylosed more frequently than the first molars (P < 0.001). No statistical significance was found between sex and number of infraoccluded teeth (P = 0.74). CONCLUSION: This study found an incidence of deciduous molar ankylosis of about 6.6%; the lower deciduous molars and second deciduous molars were ankylosed more frequently (P < 0.001).

Genetic basis of non syndromic hypodontia: a DNA investigation performed on three couples of monozygotic twins about PAX9 mutation.

INTRODUCTION: Hypodontia, agenesis of one or of more teeth, is a common developmental dental anomaly. To date, over 200 candidate genes have been demonstrated to be active in tooth development. The genes Pax9 plays an important role in the initial stage of odontogenesis. Mutations of Pax9 are associated with autosomal dominant forms of oligodontia, the agenesis of more than six teeth and occasionally of premolars (MIM 604625) in humans. The aim of the present study was to screen the candidate gene causing the non syndromic hypodontia, with agenesis of upper third molars and upper lateral incisors, in three couples of twins. MATERIALS AND METHODS: Peripheral blood samples taken for routine laboratory investigations were used for genotyping. Total genomic DNA was extracted from the buffy coat of 1 ml of EDTA blood samples using phenol-chloroform and the salting out procedure. RESULTS: The insC mutation (nt793, exon4) was observed in the sequencing results by the use of the primers hPAX9ex4F and hPAX9ex4R. InsC raises a frameshift mutation that introduces a nonsense codon so the mRNA activity results impaired. CONCLUSION: In this work, it is described how the same mutation is responsible for a form of dental agenesis--less severe in the number of missing teeth--leading to hypodontia instead of oligodontia. Therefore, it is possible that mutations of the same gene cause different phenotypes; so we can presume that some modifier genes moderate the effect of the first mutation.

Effect of interferon on growth and division cycle of Friend erythroleukemic murine cells in vitro.

The administration of appropriate doses of interferon to cultures of Friend leukemia cells causes a pronounced inhibition of cell growth. Several lines of evidence indicate that this effect is due to interferon itself, rather than to unknown contaminants of interferon preparations. Autoradiograph analysis of growth parameters of Friend leukemia cells during treatment with interferon demonstrates that the rate of entry into the S phase, the percent decline of unlabeled mitoses, and the mitotic indexes are significantly lower in interferon-treated cell cultures than in control untreated cultures when tritiated thymidine was added 12 h after the administration of interferon. These data indicate that fractions of interferon-treated cell population are delayed in both G1 and in G2 phases of the cell cycle. This was confirmed by exact measurements of the length of the various phases of the cycle. The interferon-induced inhibition of growth of Friend leukemia cells is reversible after removal of the compound. Autoradiograph data obtained from control cultures and from cultures previously treated with interferon that had been washed free of interferon and reseeded in interferon-free medium, demonstrate that during the first 12 h after removal of interferon, a large majority of the cells previously treated with interferon had a deranged flow into the S phase, a high number of unlabeled mitoses, and a low mitotic index. These data provide further evidence for the above-mentioned prolongations of G1 and G2 phases of the cell cycle. All growth parameters tested reverted to normal values within 12 h after washing out interferon.

Myotonic dystrophy and craniofacial morphology: clinical and instrumental study.

AIM: The aim of this study is to assess if, and to what extent, myotonic dystrophy can affect the craniofacial growth pattern. MATERIALS AND METHODS: The research was conducted on a sample of 27 patients with Steinert's myotonic dystrophy (study group). Each subject underwent a clinical examination with impression-taking and intra- and extraoral photographs. A latero-lateral projection teleradiography in the mirror position was also taken and a cephalometric examination was performed. The assessed values were compared with those obtained from a group of healthy subjects (control group). RESULTS: Statistical analysis of the data obtained from the myotonic patients who developed the disease during the growth phase revealed alterations in the transversal plane and, to an even greater extent, the vertical one, with a high frequency of anterior open bite. Discussion and conclusions Regarding the pathogenesis of these types of skeletal dysplasias, the authors hypothesise a posterior rotation growth pattern, resulting from gravitational force prevailing over the deficit of the elevator muscles.

Evaluation of the efficacy of celecoxib and ibuprofen on postoperative pain, swelling, and mouth opening after surgical removal of impacted third molars: a randomized, controlled clinical trial.

The objective of this study was to compare the efficacy of celecoxib and ibuprofen in reducing postoperative sequelae following the surgical removal of impacted mandibular third molars. Ninety-eight subjects who needed surgical extraction of an impacted mandibular third molar were selected for the study. All subjects were randomly allocated to receive one of the following treatments twice a day for 5days after surgery: placebo (n=32), ibuprofen (n=33), or celecoxib (n=33). The primary outcome chosen was postoperative pain, which was evaluated using the visual analogue scale (VAS) score recorded by each patient. The secondary outcomes chosen were changes in postoperative swelling and maximum mouth opening values compared to preoperative ones. Compared to placebo, treatment with celecoxib and ibuprofen resulted in improvements in the primary outcome. Furthermore, when compared to the other groups, patients in the celecoxib group showed a significant reduction in postoperative pain scores at 6h (P<0.001), 12h (P=0.011), and 24h (P=0.041) after surgery. Regarding swelling and maximum mouth opening values, there were no significant differences between the groups at each follow-up session. This study demonstrated that treatment with celecoxib decreased the incidence and severity of postoperative pain following third molar surgery compared to ibuprofen and placebo.

Glatiramer Acetate modulates ion channels expression and calcium homeostasis in B cell of patients with relapsing-remitting multiple sclerosis.

To investigate the effects of Glatiramer Acetate (GA) on B cells by an integrated computational and experimental approach. GA is an immunomodulatory drug approved for the treatment of multiple sclerosis (MS). GA effect on B cells is yet to be fully elucidated. We compared transcriptional profiles of B cells from treatment-naïve relapsing remitting MS patients, treated or not with GA for 6 hours in vitro, and of B cells before and after six months of GA administration in vivo. Microarrays were analyzed with two different computational approaches, one for functional analysis of pathways (Gene Set Enrichment Analysis) and one for the identification of new drug targets (Mode-of-action by Network Analysis). GA modulates the expression of genes involved in immune response and apoptosis. A differential expression of genes encoding ion channels, mostly regulating Ca2+ homeostasis in endoplasmic reticulum (ER) was also observed. Microfluorimetric analysis confirmed this finding, showing a specific GA effect on ER Ca2+ concentration. Our findings unveils a GA regulatory effect on the immune response by influencing B cell phenotype and function. In particular, our results highlight a new functional role for GA in modulating Ca2+ homeostasis in these cells.