Changes in the Biomarkers of Oxidative/Nitrosative Stress and Endothelial Dysfunction Are Associated with Cardiovascular Risk in Periodontitis Patients.

Patients with cardiovascular disease (CVD) and periodontitis (PT) show shared risk factors as result of the altered molecular mechanisms associated with pathological conditions. The aim of our study was to evaluate if the plasma biomarkers associated with endothelial dysfunction may also be related to alterations in the inflammatory status in peripheral blood mononuclear cells (PBMC). Patients with PT, coronary heart disease (CHD), or both diseases as well as controls were enrolled. Plasma levels of coenzyme Q10 (CoQ10), 3-nitrotyrosine (NT), and asymmetric dimethylarginine (ADMA) were assessed using HPLC. mRNA levels of caspase-1 (CASP1), NLR family pyrin domain containing 3 (NLRP3), and tumor necrosis factor-α (TNF-α) in PBMC from the recruited subjects were quantified using real-time PCR. Patients with PT + CHD showed lower CoQ10 plasma levels and increased concentrations of NT in comparison to healthy subjects. ADMA levels were higher in CHD and PT + CHD patients compared to controls. Transcript levels of CASP1, NLRP3, and TNF-α were up-regulated in PBMC from all patient groups when compared to healthy subjects. Our results suggest a possible causal link between oxidative stress, high levels of NT and ADMA, and inflammasome activation, which may be involved in the endothelial inflammatory dysfunction leading to the pathogenesis and progression of CHD in PT patients.

Baicalin-Induced Autophagy Preserved LPS-Stimulated Intestinal Cells from Inflammation and Alterations of Paracellular Permeability.

Several studies have demonstrated a relevant role of intestinal epithelial cells in the immune response and in chronic inflammatory conditions, including ulcers, colitis, and Crohn's disease. Baicalin (BA), extracted from the root of Scutellaria baicalensis, has various beneficial healthy effects, including anti-inflammatory activity. However, few studies have evaluated BA effects on autophagic signaling in epithelial cell response to inflammatory stimuli. To explore possible beneficial effects of BA, HT-29 cells were exposed to lipopolysaccharide (LPS), in presence or absence of BA, for 4 h. We evaluated mRNA levels of autophagy-related genes and cytokines, triggering inflammatory response. Furthermore, the expression of claudin 1, involved in the regulation of paracellular permeability was analyzed. BA treatment repressed LPS-induced expression of TNF-α and IL-1ß. The down-regulation of autophagy-related genes induced by LPS was counteracted by cell pretreatment with BA. Under these conditions, BA reduced the NF-κB activation caused by LPS. Also, BA restored mRNA and protein levels of claudin 1, which were reduced by LPS. In conclusion, in intestinal epithelial cells BA regulates the NF-κB activation and modulates both autophagic and inflammatory processes, leading to an improvement of paracellular permeability. These results suggest that the anti-inflammatory effects of BA can be associated to the regulation of autophagic flux.

Comparison of Effectiveness of Etoricoxib and Diclofenac on Pain and Perioperative Sequelae After Surgical Avulsion of Mandibular Third Molars: A Randomized, Controlled, Clinical Trial.

OBJECTIVE: The objective of this analysis was to compare the efficacy of etoricoxib and diclofenac in the management of perioperative sequelae following impacted mandibular third molar surgery. MATERIALS AND METHODS: Ninety-seven patients who needed surgical avulsion of an impacted mandibular third molar were chosen for the study. All patients were randomly allocated to receive one of the following treatments, twice a day for 5 days after surgery: placebo (n=33), diclofenac (n=32), or etoricoxib (n=32). The primary outcome evaluated was postoperative pain, recorded by each patient and evaluated using the Visual Analogue Scale score. The secondary outcomes chosen were, compared with preoperative ones, changes in postoperative swelling and maximum mouth opening. RESULTS: Compared with placebo, treatment with etoricoxib and diclofenac demonstrated an enhancement in the primary outcome. Furthermore, when compared with the other groups, patients who had undergone etoricoxib presented a significant median reduction in postoperative pain at 2 hours (P<0.001), 12 hours (P=0.025), and at 48 hours (P=0.018) after surgery. Moreover, the linear regression analysis showed that diclofenac and etoricoxib determined a significant influence on Visual Analogue Scale at 2, 6, 12, 24, 48 hours and at 10 days after surgery. There were no differences in swelling and maximum mouth opening values between groups. DISCUSSION: This study demonstrated that both treatments were effective. However, treatment with etoricoxib showed a greater reduction in the incidence and severity of postoperative pain following third molar surgery compared with diclofenac and placebo.

Efficacy of a drug composed of herbal extracts on postoperative discomfort after surgical removal of impacted mandibular third molar: a randomized, triple-blind, controlled clinical trial.

OBJECTIVES: This study investigated and compared the effectiveness of a phytotherapeutic drug composed of herbal extracts on postsurgical discomfort after mandibular third molar surgery. MATERIALS AND METHODS: Eighty-two patients requiring the surgical removal of a mandibular third molar were randomly assigned to receive placebo (group 1), ibuprofen (group 2), and a phytotherapeutic drug (composed of baicalin, 190 mg; bromelain, 50 mg; escin, 30 mg) (group 3). Drugs were administered after tooth extraction twice a day for 5 days. The primary outcome, pain, was evaluated using a visual analogue scale at 2 h, 6 h, 12 h, 24 h, 48 h, and 7 and 10 days after surgery. The secondary outcomes were the changes in maximum mouth opening and facial contours (mm) between baseline and at 24 h, 72 h, and 7 and 10 days after surgery. RESULTS: Compared to the baseline, all treatments demonstrated an improvement in the primary and secondary outcomes. Moreover, compared to groups 1 and 2, patients in group 3 yielded a significant reduction of the postoperative pain score at 12 h (p < 0.001), 24 h (p = 0.010), and 48 h (p = 0.048) after surgery. The mean reduction of the swelling and trismus was similar between groups. CONCLUSIONS: The results of this study suggest that a postoperative administration of a phytotherapeutic drug was found to be effective in postoperative pain management after the surgical removal of impacted mandibular third molars. CLINICAL RELEVANCE: The phytotherapeutic drug composed of herbal extract determined a decrease in the severity of postoperative pain compared to ibuprofen and placebo.

Clinical Efficacy and Patient Perceptions of Pyogenic Granuloma Excision Using Diode Laser Versus Conventional Surgical Techniques.

The use of laser in oral surgery and periodontology is a matter of debate, mainly because of the lack of consensual therapeutic protocols. The aim of this study was to evaluate the surgical advantages of diode laser versus traditional surgery with a cold blade for the surgical excision of pyogenic granuloma (PG). Twenty-one patients (10 males, 11 females, aged 19-66 years; mean age: 46.5 years), requiring PG excision, were enrolled in the study. Through a randomized clinical trial design, all patients were randomly subjected to PG surgical excision with either diode laser or cold blade. Parameters analyzed were the speed of incision, time of intervention, intraoperative bleeding, number of stitches, and patient compliance. Histologic examination was performed before and after surgical excision of the lesions. Patients compiled a subjective evaluation questionnaire. Both treatments were successful in surgical excision of PG. However, the mean speed of incision was significantly reduced in diode laser group (0.61 ±â€Š0.29 mm/s) compared with cold blade group (1.47 ±â€Š1.23 mm/s) (P < 0.05). The mean lengths of time for the whole surgical intervention were significantly lower in diode laser group (221.15 ±â€Š220.89 s) compared with cold blade group (316.10 ±â€Š248.69 s) (P < 0.05). Moreover, diode laser induced a reduced intrasurgical bleeding, and a better gingival healing compared with cold blade surgical treatment. This study demonstrated that the use of diode laser showed additional advantages compared with cold blade in terms of less postoperative discomfort and pain for surgical removal of PG.

Implantology and Periodontal Disease: The Panacea to Problem Solving?

INTRODUCTION: The specialty of periodontology has changed dramatically in recent years. With the long-standing goal of retaining teeth in a functional and esthetical state, the periodontology has developed a high level of expertise in the regeneration of bone and connective tissues that support the teeth. However, periodontists have also joined maxillofacial surgeons as the primary providers of implant surgery. METHODS: The tremendous innovations of periodontists induced also by the marketplace resulted in predictable periodontal treatment outcomes for most patients by the implants led to a dramatically different marketplace in which many patients with periodontitis can be treated by the implants rather than the traditional periodontal treatment. RESULTS: The aim of this article is to focus on the innovator's dilemma for periodontists today is that key elements of our rewarding contributions to dentistry in recent decades are unlikely to be part of a strong and rewarding future for the profession. CONCLUSIONS: With the intriguing role of the personalized medicine approach that integrates genomic and clinical information to predict a possible predisposition, we do not suggest a reduced role for periodontists in dental implant surgery but rather a more prominent role in complex cases to achieve surgical implant needs and proper reconstruction and long-term maintenance of the patient's health.

The Effects of Diode Laser Therapy as an Adjunct to Scaling and Root Planing in the Treatment of Aggressive Periodontitis: A 1-Year Randomized Controlled Clinical Trial.

OBJECTIVE: The aim of this study was to investigate and compare the clinical, microbial, and inflammatory effects of a diode laser as an adjunct to scaling and root planing (SRP) versus SRP alone for the treatment of generalized aggressive periodontitis (GAgP). METHODS: Using a split-mouth design, 31 patients with GAgP were enrolled in the study. The maxillary right and left quadrants were randomly assigned to SRP+diode laser or SRP alone. Patients were examined on a regular basis for clinical, microbiological, and inflammatory mediator changes over a 1-year period. Clinical attachment level (CAL) was the primary outcome variable chosen. In addition, subgingival biofilm samples and gingival crevicular fluid (GCF) inflammatory mediators were analyzed at each follow-up session. RESULTS: Compared to baseline, both treatments demonstrated an improvement in periodontal parameters at 1 year. However, SRP+diode laser produced a significant improvement in probing depth (PD; 2.56 ± 0.44 vs. 3.36 ± 0.51 mm, p < 0.05) and CAL (3.47 ± 0.25 vs. 4.11 ± 0.26 mm, p < 0.05) values compared to SRP alone. Similarly, in the SRP+diode laser group, the bacteria of orange complex group were significantly reduced at 30 and 60 days compared to SRP alone. Moreover, SRP+diode laser determined a reduction in mean GCF level of interleukin (IL)-1ß and IL-1ß/IL-10 ratio at 15 and 30 days compared to SRP alone (p < 0.05). CONCLUSIONS: At 1 year, SRP+diode laser yielded a significant reduction in some clinical parameters, while microbial and inflammatory mediator changes were not significantly reduced compared to SRP alone.

Association Between Odontoma and Impacted Teeth.

Odontoma is considered to be the most common odontogenic tumor of the oral cavity. Most odontomas are asymptomatic and are discovered during routine radiographic investigations and can cause disturbances in the eruption of the teeth, most commonly delayed eruption or deflection. By a retrospective study design, demographic and clinical data regarding patients who presented odontomas from year 1995 to 2015 were obtained in order and the influence of active therapy on the dentition and on the treatment of impacted teeth was analyzed. Forty-five patients (mean age 14.2 years) with 29 complex and 16 compound odontomas were included in this retrospective study. Initial symptoms were delayed eruption of permanent teeth (n = 25), pain (n = 6), swellings (n = 4), and no symptoms (n = 10); 31 patients were discovered by incidence, all of them via panoramic radiographs. The mandible/maxilla ratio was about 2:1 (31/15). Thirty-two out of 45 odontomas were in close proximity of at least 1 tooth (n = 21 at incisive). A total of 12 teeth were extracted (complex: n = 8; compound: n = 4). Of the nonextracted teeth, 33 teeth were displaced and retained. Of those, 29 teeth were aligned through orthodontic-surgical approach and 4 teeth erupted spontaneously after surgery during the follow-up period. An early detection of odontoma is more likely an accidental radiological finding, hence the need for routine radiographic analysis should be emphasized. Early diagnosis of odontomas in primary dentition is crucial in order to prevent later complications, such as impaction or failure of eruption of teeth.

Influence of MTHFR Genetic Background on p16 and MGMT Methylation in Oral Squamous Cell Cancer.

Genetic polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) enzyme may influence DNA methylation. Alterations in DNA methylation patterns of genes involved in the regulation of the cell cycle, DNA repair, cell adherence and metastasis process are known to contribute to cancer development. In this study, the influence of the MTHFR C677T and A1298C gene polymorphisms on global DNA methylation and site-specific methylation on p16 and O6-methylguanine-DNA methyltransferase (MGMT) gene promoters was investigated in patients with oral squamous cell cancer (OSCC). To this aim, methylation studies were carried out by using genomic DNA isolated from saliva samples of 58 OSCC patients and 90 healthy controls. The frequency of the CT/AC and TT/AA genotypes was significantly higher in patients than in controls. Whereas no difference in global DNA methylation levels was observed between patients and controls, a higher frequency of methylation at both p16 and MGMT gene promoters was detected in patients compared with controls. A significant association between MTHFR gene polymorphisms and p16 and MGMT gene promoter methylation was found. The frequency of p16 and MGMT methylation was around 60% in patients with either the CT/AC or TT/AA genotype. Our results suggest that hypermethylation of cancer-related genes may be affected by MTHFR polymorphisms.

A New Approach for the Treatment of Lateral Periodontal Cysts with an 810-nm Diode Laser.

The aim of this study was to test whether the combination of diode laser therapy and surgical treatment for a lateral periodontal cyst (LPC) would result in greater clinical improvement compared with surgery alone. A total of 18 patients with LPCs were assessed for eligibility for this study. At baseline, each patient was randomly allocated to one of two regimens: diode laser plus surgery (test group) or traditional surgical treatment alone (control group). Healing parameters were assessed at 7 to 21 days to monitor short-term complications, and periodontal parameters were assessed at 3, 6, and 12 months to evaluate long-term healing. The test group demonstrated highly significant differences in both the short-term and long-term parameters compared with the control group. This study showed that diode laser treatment results in a shorter wound-healing period and could be considered valuable for the surgical treatment of LPCs.

Reliability and efficacy of palifermin in prevention and management of oral mucositis in patients with acute lymphoblastic leukemia: a randomized, double-blind controlled clinical trial.

BACKGROUND: Myeloablative and hematopoietic stem cells transplantation therapy (HSCT) often acts as side-effect to oral mucositis (OM) with no effective treatment. This randomized-controlled trial analyzed the efficacy of palifermin, administered as a dose during HSCT therapy, as primary prophylaxis on pediatric patients with acute lymphoblastic leukemia (ALL). METHODS: In this study forty-six patients (9-15 years) with B-cell acute lymphoblastic leukemia (B-ALL) were analyzed. The patients underwent allogenic HSCT conditioned by myeloablative regimen. Subsequently to randomization, patients in the palifermin group were assigned to receive palifermin, 60 mg/kg, intravenously as a single dose 3 days before and after transplant conditioning regimen cycle. The patients in the Control group received only a placebo treatment. Maximum severity of OM, incidence and duration of ulcerative OM, incidence and duration of severe OM limitations were evaluated. RESULTS: A statistically significant reduction in the incidence of OM up to grade 3 in the palifermin group compared to the control group was discovered. There was also a reduction, confirmed at 60 days, in the degree of severity of mucositis in the palifermin group, with an average of 1.54 grade in the palifermin group, and of 2.16 in the Control group and in the use of opioid analgesics. CONCLUSIONS: This study indicates that a single dose of palifermin used as primary prophylaxis during HSTC therapy can prevent severe OM in pediatric patients with ALL and used as secondary prophylaxis can prevent the recurrence of severe OM in high-risk patients with previous mucosal injury and improves the quality of life in pediatric patients with ALL.

Efficacy and effects of palifermin for the treatment of oral mucositis in patients affected by acute lymphoblastic leukemia.

This randomized-controlled trial studied the efficacy of palifermin, administered as a dose during hematopoietic stem cell transplant (HSCT) therapy, as primary prophylaxis on pediatric patients with acute lymphoblastic leukemia in order to reduce oral mucositis (OM). Patients in the palifermin group were randomly assigned to receive palifermin, 60 µg/kg, intravenously as a single dose 3 days before and 0, +1, and +2 post autologous HSCT infusion. The patients in the control group received only a placebo treatment. OM-related assessments were the WHO oral-toxicity scale and the patient-reported outcomes. There was a statistically significant reduction in the incidence of OM grade 3 and 4 in the palifermin group compared to the control group. There was also a reduction in the degree of severity of OM in the palifermin group (1.65 grade respect to 2.33 in the control group). Palifermin could prevent the recurrence of severe OM and improve the quality of life in patients with acute lymphoblastic leukemia (ALL).

Transglutaminase 2 up-regulation is associated with RANKL/OPG pathway in cultured HPDL cells and THP-1-differentiated macrophages.

Recent evidence emphasized that transglutaminase 2 (TG2), a protein cross-linking enzyme, may play a role in the early phase of inflammation. High levels of TG2 have been associated with the constitutive activation of nuclear factor-kappa B (NF-κB) that is considered the main regulator of inflammation. In this context, the receptor activator of NF-kappa B ligand (RANKL) and receptor activator of NF-κB have extensive functions in the regulation of cytokine secretion associated with different pathological conditions. The human periodontal ligament (HPDL) cells, which express and secrete osteoprotegerin (OPG) and RANKL, represent an useful "ex vivo" model for monitoring cell response in inflammatory microenvironments, such as periodontitis-dependent tissue response. Thus, we evaluated TG2 expression and alterations in RANKL/OPG ratio occurring in cultured HPDL cells. The HPDL cells were obtained from patients with chronic periodontitis (CP) and healthy subjects. We observed the up-regulation of some inflammatory markers, such as IL-6, TNF-α, and HMGB-1, and at the same time an increase in TG2 mRNA levels in HPDL cells from CP patients compared with healthy subjects. We found a positive correlation between RANKL/OPG ratio and TG2 mRNA levels in HPDL cells from CP patients. In the parallel experiments, we demonstrated that TG2 inhibition reduced RANKL expression in both HPDL cells from CP patients and monocytes differentiated to macrophages by tetradecanoyl phorbol acetate treatment. Given the RANKL key role in NF-κB pathway and the observed up-regulation of pro-inflammatory cytokines, our data suggest that TG2 may be involved in molecular mechanisms of inflammatory response occurring in periodontal disease.

Influence of bracket-slot design on the forces released by superelastic nickel-titanium alignment wires in different deflection configurations.

OBJECTIVE: To evaluate how different bracket-slot design characteristics affect the forces released by superelastic nickel-titanium (NiTi) alignment wires at different amounts of wire deflection. MATERIALS AND METHODS: A three-bracket bending and a classic-three point bending testing apparatus were used to investigate the load-deflection properties of one superelastic 0.014-inch NiTi alignment wire in different experimental conditions. The selected NiTi archwire was tested in association with three bracket systems: (1) conventional twin brackets with a 0.018-inch slot, (2) a self-ligating bracket with a 0.018-inch slot, and (3) a self-ligating bracket with a 0.022-inch slot. Wire specimens were deflected at 2 mm and 4 mm. RESULTS: Use of a 0.018-inch slot bracket system, in comparison with use of a 0.022-inch system, increases the force exerted by the superelastic NiTi wires at a 2-mm deflection. Use of a self-ligating bracket system increases the force released by NiTi wires in comparison with the conventional ligated bracket system. NiTi wires deflected to a different maximum deflection (2 mm and 4 mm) release different forces at the same unloading data point (1.5 mm). CONCLUSION: Bracket design, type of experimental test, and amount of wire deflection significantly affected the amount of forces released by superelastic NiTi wires (P<.05). This phenomenon offers clinicians the possibility to manipulate the wire's load during alignment.

Load-deflection characteristics of superelastic and thermal nickel-titanium wires.

The aim of this study was to investigate the mechanical properties of superelastic and thermal nickel-titanium (NiTi) archwires for correct selection of orthodontic wires. Seven different NiTi wires of two different sizes (0.014 and 0.016 inches), commonly used during the alignment phase, were tested. A three-point bending test was carried out to evaluate the load-deflection characteristics. The archwires were subjected to bending at a constant temperature of 37°C and deflections of 2 and 4 mm. Analysis of variance showed that thermal NiTi wires exerted significantly lower working forces than superelastic wires of the same size in all experimental tests (P < 0.05). Wire size had a significant effect on the forces produced: with an increase in archwire dimension, the released strength increased for both thermal and superelastic wires. Superelastic wires showed, at a deflection of 2 mm, narrow and steep hysteresis curves in comparison with the corresponding thermal wires, which presented a wide interval between loading and unloading forces. During unloading at 4 mm of deflection, all wires showed curves with a wider plateau when compared with 2 mm deflection. Such a difference for the superelastic wires was caused by the martensite stress induced at higher deformation levels. A comprehensive understanding of mechanical characteristics of orthodontic wires is essential and selection should be undertaken in accordance with the behaviour of the different wires. It is also necessary to take into account the biomechanics used. In low-friction mechanics, thermal NiTi wires are to be preferred to superelastic wires, during the alignment phase due to their lower working forces. In conventional straightwire mechanics, a low force archwire would be unable to overcome the resistance to sliding.

Immunohistochemical analysis of TGF-ß1 and VEGF in gingival and periodontal tissues: a role of these biomarkers in the pathogenesis of scleroderma and periodontal disease.

Periodontal disease is characterized by inflammation and bone loss. The balance between inflammatory mediators and their counter-regulatory molecules may be fundamental for determining the outcome of the immune pathology of periodontal disease. Transforming growth factor-ß (TGF-ß) and vascular endothelial growth factor (VEGF) represent a family of polypeptide proteins involved in the inflammation and regulation of immune responses, especially in rheumatic disease. The relationship between these growth factors and periodontitis has resulted in a new field of osteoimmunology and provides a context for better understanding the pathogenesis of periodontal disease. Therefore, the aim of this study was to compare the protein expression profile of these inflammatory mediators in 90 patients divided in three groups: healthy control, chronic periodontitis and in rheumatic disease, scleroderma. The findings presented here highlight that biomarkers, such as TGF-ß1 and VEGF, play a key role in the evolution of the immune response, which in turn influences the outcome of disease establishment.

Biomonitoring of DNA damage in peripheral blood lymphocytes of subjects with dental restorative fillings.

Dental fillings provide a major iatrogenic exposure to xenobiotic compounds due to the high prevalence of surface restorations in developed countries. Experimental data suggest that both amalgams, which contain mercury, and resin-based dental materials cause an impairment of the cellular pro- and anti-oxidant redox balance. The aim of this study was to assess the potential genotoxicity of dental restorative compounds in peripheral blood lymphocytes of young exposed subjects compared with controls. The study examined, by use of the comet assay, 68 carefully selected subjects taking into account the major known confounding factors. In the 44 exposed subjects, the mean numbers of restored surfaces was 3.0 and 3.8 in males and females, respectively. Tail length, percentage of DNA in the tail, tail moment or Olive tail moment were twofold higher in the exposed group than in unexposed controls, with significant differences. No significant difference was observed between amalgam and composite fillings. Furthermore, as shown by multivariate analysis, the association between dental fillings and DNA damage was enhanced by the number of fillings and by the exposure time. Among the lifestyle variables, a moderate physical activity showed a protective effect, being inversely correlated to the DNA damage parameters evaluated. On the whole, the use of DNA-migration allowed us to detect for the first time the potential adverse impact on human health of both kinds of dental filling constituents, the amalgams and the methacrylates. The main mechanism underlying the genotoxicity of dental restorative materials of various nature may be ascribed to the ability of both amalgams and methacrylates to trigger the generation of cellular reactive oxygen species, able to cause oxidative DNA lesions.