Anti-inflammatory effect of salt water and chlorhexidine 0.12% mouthrinse after periodontal surgery: a randomized prospective clinical study.

OBJECTIVES: The purpose of this study was to compare the anti-inflammatory efficacy of sodium chloride- and a 0.12% chlorhexidine mouth rinses in patients undergoing minimal invasive periodontal surgery. MATERIALS AND METHODS: Forty-seven patients with a diagnosis of periodontitis and indication for access flap procedure were randomly selected. Group A: a sodium chloride (salt)water-based mouth rinse (test group) or group B: a 0.12% chlorhexidine mouth rinse (control group) administered after surgery. Gingival Index (GI) were evaluated in the whole mouth and in the surgical site at baseline (T1), a week later (T2), and 12 weeks (T3) after the treatment. Total MMP activity was measured in GCF using a commercial kit and plate reader. Medians of total MMP activity and GI were compared for time intervals T1 vs. T2, T1 vs. T3, and T2 vs T3 using Friedman tests and Wilcoxon signed rank tests, and were also compared between test and control using Mann-WhitneyU tests at each timepoint. RESULTS: The average GI values showed significant differences between baseline and T2 (p = 0.0005) and baseline and T3 (p = 0.003) in the test group. CONCLUSION: The sodium chloride-mouth rinse use after periodontal surgery seems to have similar anti-inflammatory properties as CHX mouth rinse and can be used regularly postoperatively after periodontal surgical procedures. CLINICAL RELEVANCE: The use of salt water mouthwash showed an anti-inflammatory effect similar to CHX 0.12% after minimal invasive periodontal surgery. Salt water mouthwash is accessible to the world population and can contribute on the healing process after periodontal surgery.

Efficacy of a Novel Pleiotropic MMP-Inhibitor, CMC2.24, in a Long-Term Diabetes Rat Model with Severe Hyperglycemia-Induced Oral Bone Loss.

Purpose: CMC2.24, a novel 4-(phenylaminocarbonyl)-chemically-modified-curcumin, is a pleiotropic MMP-Inhibitor of various inflammatory/collagenolytic diseases including periodontitis. This compound has demonstrated efficacy in host modulation therapy along with improved resolution of inflammation in various study models. The objective of current study is to determine the efficacy of CMC2.24 in reducing the severity of diabetes, and its long-term role as an MMP-inhibitor, in a rat model. Methods: Twenty-one adult male Sprague-Dawley rats were randomly distributed into three groups: Normal (N), Diabetic (D) and Diabetic+CMC2.24 (D+2.24). All three groups were orally administered vehicle: carboxymethylcellulose alone (N, D), or CMC2.24 (D+2.24; 30mg/kg/day). Blood was collected at 2-months and 4-months' time-point. At completion, gingival tissue and peritoneal washes were collected/analyzed, and jaws examined for alveolar bone loss by micro-CT. Additionally, sodium hypochlorite(NaClO)-activation of human-recombinant (rh) MMP-9 and its inhibition by treatment with 10µM CMC2.24, Doxycycline, and Curcumin were evaluated. Results: CMC2.24 significantly reduced the levels of lower-molecular-weight active-MMP-9 in plasma. Similar trend of reduced active-MMP-9 was also observed in cell-free peritoneal and pooled gingival extracts. Thus, treatment substantially decreased conversion of pro- to actively destructive proteinase. Normalization of the pro-inflammatory cytokine (IL-1ß, resolvin-RvD1), and diabetes-induced osteoporosis was observed in presence of CMCM2.24. CMC2.24 also exhibited significant anti-oxidant activity by inhibiting the activation of MMP-9 to a lower-molecular-weight (82kDa) pathologically active form. All these systemic and local effects were observed in the absence of reduction in severity of hyperglycemia. Conclusion: CMC2.24 reduced activation of pathologic active-MMP-9, normalized diabetic osteoporosis, and promoted resolution of inflammation but had no effect on the hyperglycemia in diabetic rats. This study also highlights the role of MMP-9 as an early/sensitive biomarker in the absence of change in any other biochemical parameter. CMC2.24 also inhibited significant activation of pro-MMP-9 by NaOCl (oxidant) adding to known mechanisms by which this compound treats collagenolytic/inflammatory diseases including periodontitis.

Clinical and Radiographic Evaluation of a Novel Triangular Implant Neck Design: A Case Series.

The objective of this study was to evaluate the clinical and radiographic behavior of a novel triangular neck implant configuration in partially edentulous patients. Sixteen patients with a mean age of 58.3 years, were rehabilitated with 25 implants inserted in the healed sites of the maxilla and mandible; implant diameter was Ø3.3 and 3.9 mm. Clinical and radiographic measurements were first performed at prosthesis delivery that served as baseline; they were further evaluated after a mean period of 15.6 months. The interproximal peri-implant bone levels were the primary outcome; the mesial and distal data were recorded and a mean value was calculated. Secondary outcomes included peri-implant probing depth (PPD) and bleeding on probing (BoP). The paired t-test was used to compare the radiographic and clinical outcomes between baseline and follow-up. The mean bone levels at the mesial and distal aspects at baseline were 0.45 (0.47) and 0.57 (0.69), respectively; at follow-up they were 0.59 (0.42) and 0.78 (0.59), respectively. The differences were not statistically significant. Similarly, no significant differences were found for the clinical parameters. Within the limitations of the present study, it could be concluded that this new triangular neck bone level implant macro-design was used successfully to treat partially edentulous patients. Larger controlled clinical studies are warranted to confirm the present radiographic and clinical findings.

Efficacy of Nd:YAG laser-assisted periodontal therapy for the management of periodontitis: A double-blind split-mouth randomized controlled clinical trial.

BACKGROUND: This study aimed to explore the efficacy of Nd:YAG laser-assisted periodontal therapy for management of patients with stage II-IV periodontitis. METHODS: Patients who presented with residual periodontal pockets were enrolled. After non-surgical periodontal therapy (NSPT), test sites received Nd:YAG laser (first entrance to pocket: 3 W, 100 µs, 20 Hz; second entrance: 4 W, 600 µs, 20 Hz) and control sites received placebo (laser off). Periodontal probing depth (PPD), clinical attachment level (CAL), gingival recession (GR), bleeding on probing (BOP), and plaque index (PI) were recorded at baseline and 1, 2, 3, 4 and 6-month visits. RESULTS: Twenty patients completed the 6-month period. Significant reductions in PPD, CAL, BOP, and PI values and a significant increase in GR at all follow-up visits compared to the baseline (all P < 0.001) were revealed in both groups. Test sites showed significantly greater improvement in PPD (P = 0.0002) and greater increase in GR (P < 0.0001) compared to the control sites at 6-month visit. There was no difference between two groups regarding CAL gain through the study period (P = 0.23). CONCLUSION: NSPT+Nd:YAG laser with the current protocol results in greater PPD reduction compared to NSPT alone. However, this reduction is likely because of greater GR rather than attachment gain. Therefore, the adjunction of Nd:YAG laser (with the current setting) to the NSPT for the treatment of residual periodontal pockets did not ameliorate the clinical outcomes (ClinicalTrials.gov ID: NCT03365167).

Therapeutic potential of a novel semi-synthetic-sulfated-polysaccharide to suppress inflammatory mediators in P. gingivalis LPS stimulated human monocytes/macrophages.

BACKGROUND: Chronic periodontitis is associated with an increased risk for systemic conditions such as cardiovascular disease, diabetes, and osteoporosis. During chronic periodontitis, endotoxin (lipopolysaccharide, LPS) produced by P. gingivalis provokes monocyte accumulation and differentiation into macrophages and increased secretion of pro-inflammatory cytokines and matrix metalloproteases (MMPs). While normal levels of MMPs are important in cellular function, increased levels of cytokines and MMPs can cause connective tissue destruction. RESULTS: In the current study, we investigated the therapeutic capability of a novel semi-synthetic sulfated polysaccharide (SAGE) on the production of cytokines and MMPs by cultured human mononuclear cells and macrophages stimulated with endotoxin LPS produced by P. gingivalis, a periodontally-relevant cell culture model. Our research demonstrated SAGE inhibited the LPS induced synthesis of inflammatory mediators including TNF-α, IL-1ß, PGE2, and MMP-9 in this periodontal-relevant cell culture model. In addition, TLR-2 and TLR-4 levels were also reduced with the SAGE treatment. CONCLUSIONS: The therapeutic potential of this novel semi-synthetic sulfated polysaccharide compound may help to prevent tissue damage and bone loss in patients with periodontal disease or other inflammatory diseases.

Chemically-Modified Curcumin 2.24: A Novel Systemic Therapy for Natural Periodontitis in Dogs.

PURPOSE: To determine the effect of a pleiotropic MMP-inhibitor, a novel chemically-modified curcumin 2.24 (CMC2.24), on the clinical and biological measures of naturally-occurring periodontitis in the beagle dog. METHODS: Eight adult female dogs with generalized periodontitis were distributed into two groups: Placebo and Treatment (n=4/group). After a 1-hr full-mouth scaling and root planing (SRP) at time 0, placebo or CMC2.24 (10mg/kg) capsules were orally administered once/day for 3 months. Various clinical periodontal parameters (e.g., pocket depth, gingival index) were measured at different time periods (0, 1, 2 and 3 months), and gingival crevicular fluid (GCF) samples and gingival tissue biopsies (3-month) were analyzed for cytokines, MMPs and cell-signaling molecules. Standardized radiographs were taken at 0 and 3-month; in addition, peripheral blood monocytes/macrophages from these dogs at 3-month were cultured and analyzed for the pro-, activated-, and total-forms of both MMP-2 and MMP-9. RESULTS: CMC2.24 treatment significantly reduced gingival inflammation (gingival index, GCF flow), pocket depth (PD), and the numbers of pockets (PD≥4mm), compared to placebo. CMC2.24 also significantly reduced MMP-9 and MMP-2 (primarily in the activated-form) in gingival tissue, alveolar bone loss, and reduced GCF IL-1ß. Cell-signaling molecules, TLR-2 (but not TLR-4) and p38 MAPK, responded to CMC2.24 in a pattern consistent with reductions in inflammation and collagenolysis. In culture, CMC2.24 had no effect on pro-MMP-9 but essentially completely blocked the conversion of pro- to activated-MMP-9 in systemic blood-derived monocytes/macrophages from these dogs. CONCLUSION: In the beagle dog model of natural periodontitis, orally administered CMC2.24 (a novel triketonic phenylaminocarbonyl-curcumin) significantly decreased clinical measures of periodontitis as well as pro-inflammatory cytokines, MMPs, and cell-signaling molecules. These and previous studies, using other in vitro and in vivo models, support the clinical potential of CMC2.24 as a novel adjunct to SRP in the treatment of chronic periodontitis.