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.

Association of vitamin D in patients with periodontitis: A cross-sectional study.

BACKGROUND AND OBJECTIVE: Vitamin D has been considered to possess anti-inflammatory and antimicrobial activity, which may be a link for the known interaction of periodontitis (CP) and coronary heart disease (CHD). This study investigated the association between serum vitamin D levels and periodontitis in patients with CP and with CHD. Furthermore, the objective was to determine whether periodontitis and CHD had an impact on serum vitamin D levels. MATERIAL AND METHODS: Using a cross-sectional design, a total of 46 patients with CP, 45 patients with CHD, 45 patients with both CP and CHD, and 43 healthy patients were enrolled in the present study. RESULTS: Patients in the CP (17.4 ± 5.2 ng/mL) and in the CP + CHD (16.5 ± 5.6 ng/mL) group presented a significantly lower mean serum level of 25(OH)vitamin D compared to patients in the CHD (24.6 ± 3.7 ng/mL) and healthy control groups (29.9 ± 5.4 ng/mL) (P < .001). 25(OH)vitamin D levels were positively correlated with the number of teeth and negatively with C-reactive protein (CRP) and all periodontal parameters (P < .001). In all patients, there was a proportional increase of 25(OH)vitamin D levels with a progressive increase in number of teeth (P-trend <.001) while there were a proportional decrease in 25(OH)vitamin D levels with a progressive increase in clinical attachment level (CAL, P-trend = .001), probing depth (PD, P-trend = .006), and bleeding sites (BOP, P-trend <.001) levels. CONCLUSION: Patients with CP and CP + CHD presented significantly lower serum levels of vitamin D compared to CHD and healthy controls. Moreover, the presence of CP negatively influenced serum vitamin D levels.

Evaluation of salivary and serum asymmetric dimethylarginine (ADMA) levels in patients with periodontal and cardiovascular disease as subclinical marker of cardiovascular risk.

BACKGROUND: Asymmetric dimethylarginine (ADMA) plays a crucial role in endothelial function and maybe a link for the known interaction of periodontitis and coronary heart disease (CHD). In this pilot study, we compared the impact of gingival health, periodontitis (CP), CHD, or of both diseases (CP + CHD) on salivary and serum ADMA levels. METHODS: The clinical and periodontal characteristics, serum, and saliva samples were collected from 35 patients with CP, 33 patients with CHD, 35 patients with both CP + CHD, and 35 healthy subjects. Levels of ADMA and C-reactive protein (CRP) were assessed with a commercially available kit. RESULTS: The median (25% and 75% percentile) concentrations of salivary and serum ADMA were significantly higher in the CHD group [serum: 1.5 (1.2 to 1.8) µmol/L; salivary 1.3 (1 to 1.7) µmol/g protein, P < 0.01] and in the CP + CHD [serum: 1.8 (1.4 to 2.0) µmol/L; salivary 1.5 (1.2 to 1.7) µmol/g protein, P < 0.001] group compared to CP patients and controls. In univariate models, CP (P = 0.034), CHD (P < 0.001), and hs-CRP (P < 0.001) were significantly associated with serum ADMA, whereas in a multivariate model, hs-CRP remained a significant predictor of serum ADMA (P < 0.001). In a multivariate model, the significant predictors of salivary ADMA levels were hs-CRP (P < 0.001) and education socioeconomic status (P = 0.042). CONCLUSIONS: Patients with CHD and CP + CHD presented higher levels of salivary and serum ADMA compared to healthy subjects and CP patients. hs-CRP was a significant predictor of increased salivary and serum ADMA levels.

Human Dental Pulp Tissue during Orthodontic Tooth Movement: An Immunofluorescence Study.

The orthodontic tooth movement is the last step of several biological processes that take place after the application of external forces. During this process, dental pulp tissue is subjected to structural and protein expression modifications in order to maintain their integrity and functional morphology. The purpose of the present work was to perform an in vivo study, evaluating protein expression modifications in the human dental pulp of patients that have undergone orthodontic tooth movement due to pre-calibrated light force application for 30 days. Dental pulp samples were extracted from molars and premolars of the control group and after 7 and 30 days of treatment; the samples were then processed for immunofluorescence reactions using antibodies against fibronectin, collagen I and vascular endothelial growth factor (VEGF). Our results show that, after 7 days of treatment, all tested proteins change their pattern expression and will reset after 30 days. These data demonstrate that the dental pulp does not involve any irreversible iatrogenic alterations, supporting the efficacy and safety of using pre-calibrated force application to induce orthodontic tooth movement in clinical practice.

Prophylaxis of Acute Attacks with a Novel Short-term Protocol in Hereditary Angioedema Patients Requiring Periodontal Treatment.

PURPOSE: C1-inhibitor (C1-INH) related hereditary angioedema (C1-INH-HAE) is a rare pathological condition caused by a deficiency or a functional alteration of serum protein C1-INH. Clinical manifestations are represented by recurrent, potentially life-threatening episodes of cutaneous or mucosal oedema. The present study analysed the effectiveness of a specific short-term prophylaxis protocol for the management of C1-INH-HAE patients requiring chronic periodontitis treatment. MATERIALS AND METHODS: Ten consecutive C1-INH-HAE patients with mild to moderate chronic periodontitis were treated by non-surgical periodontal therapy with a full-mouth scaling approach (FMS) in two sessions 24 h apart. All patients underwent a short-term prophylaxis protocol of acute attacks based on the association of attenuated androgen (danazol), from 5 days before the first FMS session to 2 days after the second FMS session, and C1-INH concentrate given 1 h before the first FMS session. Patients were examined for periodontal changes over a 6-month period. RESULTS: None of patients developed complications or oedema up to 1 week postoperatively. Compared to baseline, scaling and root planing (SRP) treatment yielded, at 6 months, a statistically significant improvement in probing depth (PD) (baseline: 5.24 mm ± 0.85 mm vs 6 months: 2.96 ± 0.31 mm), clinical attachment level (CAL) (baseline: 5.46 ± 0.81 vs 6 months: 3.89 ± 0.38 mm), full-mouth bleeding score (FMBS) (baseline: 27.6 ± 2.2% vs 6 months: 18.5 ± 2.1%) and in full-mouth plaque score (FMPS) (baseline: 28.6 ± 2.4% vs 6 months: 21.66 ± 3.3%). CONCLUSIONS: This study showed the clinical effectiveness of the reported prophylaxis protocol in preventing acute attacks in HAE patients requiring non-surgical periodontal treatment, with no complications up to 1 week after FMS.

Association between periodontitis and glycosylated haemoglobin before diabetes onset: a cross-sectional study.

OBJECTIVES: The aim of the present cross-sectional study was to investigate the association between serum glycosylated haemoglobin (HbA1c) levels and periodontal status in patients with periodontitis (CP) and periodontally healthy controls. Furthermore, the objectives were to determine if the periodontitis influenced the serum HbA1c levels. MATERIALS AND METHODS: A total of 93 patients with CP and 95 periodontally healthy subjects were enrolled in the present study using a cross-sectional design. At baseline, patients were examined and characterized on a regular basis for blood serum parameters and non-fasting blood samples levels. In all patients, a full periodontal examination was performed and clinical attachment loss (CAL) was the primary outcome variable chosen. The spearman correlation, a stepwise multivariable linear regression, and Jonckheere-Terpstra tests were applied in order to assess the relationship between HbA1c levels and periodontitis. RESULTS: Patients in the CP group presented a significantly higher median serum level of HbA1c [40.9 (31.2; 45.6) mmol/mol)] compared to patients in the healthy control group [35.3 (29.6; 38.6) mmol/mol)] (p < 0.001). HbA1c levels were negatively correlated with the number of teeth and positively correlated with C-reactive protein levels and all periodontal parameters (p < 0.001). Moreover, there was a significant decrease in the number of teeth when HbA1c levels increased (P-trend < 0.001), while there was a significant increase in periodontal parameters (CAL, p = 0.002); PD, p = 0.008; BOP, p < 0.001) when levels of HbA1c increased. CONCLUSIONS: Patients with CP and undiagnosed diabetes presented significantly higher serum levels of HbA1c compared to periodontally healthy controls. Moreover, the presence of periodontitis was positively correlated with serum HbA1c levels before diabetes onset. CLINICAL RELEVANCE: HbA1c levels were positively correlated with the severity of periodontitis before diabetes onset.

An immunofluorescence study on VEGF and extracellular matrix proteins in human periodontal ligament during tooth movement.

The periodontal ligament (PDL) is a highly vascularized connective tissue surrounding the root of a tooth. In particular, the PDL is continuously exposed to mechanical stresses during the phases of mastication, and it provides physical, sensory, and trophic functions. It is known that the application of orthodontic force creates a change in periodontal structures. In fact, these forces generate a pressure on the ligament that closes the vessels. The aim of this study is to observe the modifications of vascular endothelial growth factor (VEGF) in the PDL and extracellular matrix proteins after application of a pre-calibrated and constant orthodontic force at different phases of treatment. We used a 50-g NiTi coiled spring and in vivo samples of PDL of maxillary and mandibular premolars of patients subjected to orthodontic treatment. These teeth were extracted at 1, 7, 14, 21, and 30 days, respectively, by application of force. The extraction of the PDL was effectuated by scarifying the radicular surface on the pressure and tension sides. The mechanical stress induced by the application of force caused an increase in the reactive type of metabolism of extracellular matrix proteins and modulation of neoangiogenesis until restoration.

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.

Effectiveness of Low-Level Laser Therapy during Tooth Movement: A Randomized Clinical Trial.

The present study evaluated the effects of low-level laser therapy (LLLT) by means of a diode laser in accelerating orthodontic tooth movement (OTM). After extraction of the first upper premolars for orthodontic purpose, 82 maxillary canines which needed distalization were analyzed in 41 enrolled patients (21 males, 20 females, mean age 13.4 ± 2.1 years). On all experimental sites, an orthodontic force of 50/N was applied by a nickel-titanium (NiTi) closed coil spring (G&H, Franklin, IN, USA) in order to obtain the space closure. Using a split mouth randomized design, the test side was treated using a diode laser (Wiser Laser Doctor Smile, Brendola, Italy) operating at 810 nm wavelength in continuous wave mode at both the buccal and palatal side on three points/side (distal, medial and mesial) (1 W output power, continuous wave of 66.7 J/cm2, energy density of 8 J) at baseline and at 3, 7, and 14 days and every 15 days until the space closed. On the control side, the opposite selected canine was treated only using orthodontic traction. The primary outcome chosen was the overall time needed to complete the levelling and closing space, measured on a study cast. The secondary outcome chosen was the evaluation of pain levels related to tooth traction, using a Visual Analogue Scale (VAS), recorded at 3, 7, and 14 days after treatments. The mean space closures of the maxillary canines were comparable between groups [Test, 4.56 mm (95% CI 3.9-4.8); Control, 4.49 mm (95% CI 3.8-4.7), p = 0.456]. The laser group yielded less mean time [84.35 ± 12.34 days (95% CI 79.3-86)] to accomplish space closure compared to the control group [97.49 ± 11.44 days (91.7-102.3)] (p < 0.001). The test side showed a significant reduction in the average range of dental pain at 3 [Test, 5.41 (95% CI 5.1-5.6); Control, 7.23 (95% CI 6.9-7.6), p < 0.001], 7 [Test, 4.12 (95% CI 3.8-4.7); Control, 5.79 (95% CI 5.4-5.8), p < 0.001], and at 14 days [Test, 2.31 (95% CI 1.8-2.3); Control, 3.84 (95% CI 3.3-4.2), p < 0.001] after treatment (p < 0.001). This study demonstrates that the use of LLLT therapy was effective in accelerating tooth movement and reducing pain levels related to OTM.

The impact of temporomandibular joint arthritis on functional disability and global health in patients with juvenile idiopathic arthritis.

OBJECTIVES: The objective of the study was to evaluate the impact of temporomandibular joint (TMJ) arthritis on the functional disability and quality of life in patients affected by juvenile idiopathic arthritis (JIA). MATERIALS AND METHODS: Sixty-two consecutive patients with JIA with or without TMJ arthritis and 35 healthy control subjects were enrolled in the study. The demographic data, disease activity and clinical characteristics were obtained from all patients. The functional disability was assessed using the Italian version of the Childhood Health Assessment Questionnaire (C-HAQ). The oral health-related quality of life (OHRQoL) was assessed using the Child Perception Questionnaire (CPQ11-14). Possible determining factors of TMJ arthritis comprised demographic, disease characteristics and scores derived from questionnaires that were assessed by a uni and multivariable logistic regression analysis. RESULTS: Compared with patients without TMJs arthritis, JIA patients with TMJ arthritis presented higher functional disability. The multivariable logistic regression analysis performed showed that female subjects (OR = 1.5, P = 0.041), with a JIA duration over 3.9 years (OR = 2.7, P = 0.033) and presenting higher C-HAQ and CPQ11-14 scores (OR = 2.7, P = 0.012 and OR = 2.9, P = 0.015, respectively) were the greatest determining factors for TMJ arthritis. CONCLUSIONS: JIA patients with TMJ arthritis presented higher functional disability and lower OHRQoL scores compared with JIA patients without TMJ arthritis. TMJ arthritis was strongly associated with JIA duration and activity, especially in female patients.

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.

Interdisciplinary approach for a patient with unilateral cleft lip and palate.

The oral rehabilitation of patients with cleft lip and palate is a challenge. The aim of this case report was to underline the importance of a sequential interdisciplinary approach to correct functional problems and improve facial esthetics for a patient with unilateral cleft lip and palate. Few clinical reports have described this treatment in a teenager. The patient, a girl, age 12.6 years, had a complete right cleft lip and palate with a Class II molar tendency and a full Class II canine relationship on the right side, and a full Class II molar relationship with a canine Class I on the left side. Transposed, impacted, and anomalously shaped teeth and crowding added to the patient's problems. Treatment included maxillary expansion and maxillary and mandibular extractions. An interdisciplinary approach was necessary to achieve proper occlusion and better esthetics.

Histologic Evaluation of Soft and Hard Tissue Healing Following Alveolar Ridge Preservation with Deproteinized Bovine Bone Mineral Covered with Xenogenic Collagen Matrix.

The purpose of this study was to histologically evaluate new bone formation and dimensional soft tissue changes of two different healing protocols (16 weeks and 32 weeks) using deproteinized bovine bone mineral (DBBM) covered with collagen matrix (CM) for alveolar ridge preservation in the anterior esthetic zone prior to dental implant placement. Compared to baseline, both treatments yielded statistically significant differences in several clinical parameters and in the microarchitecture of the native bone and in the newly formed bone in the augmented sites. However, the protocol at 32 weeks determined greater new vital bone formation and fewer dimensional tissue changes.

The effects of a desiccant agent in the treatment of chronic periodontitis: a randomized, controlled clinical trial.

OBJECTIVE: Chemotherapeutic agents have been widely used as adjuncts for the treatment of chronic periodontitis (CP). This study investigated and compared a desiccant agent as an adjunct to scaling and root planing (SRP) versus SRP alone for the treatment of CP. MATERIALS AND METHODS: Thirty-six patients with CP were studied. Using a split-mouth design, the maxillary right and left quadrants were randomly assigned to SRP plus desiccant (Hybenx® EPIEN Medical, Inc. St. Paul, MN, USA) 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. In addition, the red complex bacteria and gingival crevicular fluid (GCF) inflammatory mediators were monitored. RESULTS: Compared to baseline, both treatments demonstrated an improvement in periodontal parameters. Compared to SRP alone, SRP plus desiccant yielded a significant improvement in probing depth (PD) (SRP: 2.23 ± 0.31 mm vs. desiccant: 3.25 ± 0.57 mm, p < 0.05), CAL (SRP: 3.16 ± 0.29 mm vs. desiccant: 4.21 ± 0.34 mm, p < 0.05 mm) and bleeding on probing (BOP) (SRP: 4.56 ± 1.5% vs. desiccant: 34.23 ± 4.2%, p < 0.001) at 12 months. Similarly, in the SRP plus desiccant group, the bacteria of the red complex were significantly reduced (p < 0.05); and the level of inflammatory mediators was significantly reduced (p < 0.003) compared to SRP alone. CONCLUSIONS: SRP plus the desiccant resulted in a greater reduction in clinical, microbial and inflammatory mediators compared to SRP alone. CLINICAL RELEVANCE: Desiccant, when combined to SRP, was demonstrated as a significant approach to control the levels of certain periodontal pathogens, inflammatory mediators in patients with CP.