Clinical and biochemical evaluation of oral irrigation in patients with peri-implant mucositis: a randomized clinical trial.

OBJECTIVE: This randomized clinical trial aimed to compare the efficacy of an oral irrigator and an interdental brush in patients with peri-implant mucositis clinically and biochemically at different time points (at baseline and at the 2nd, 4th, and 12th weeks). MATERIALS AND METHODS: Forty-five patients with at least one implant with peri-implant mucositis were included in the present study (n = 45). The patients were divided into three groups: oral irrigator + toothbrush (OI group, n = 15), interdental brush + toothbrush (IB group, n = 15), and toothbrush only (control) (C group, n = 15). The modified plaque index (mPlI), modified sulcus bleeding index (mSBI), probing pocket depth (PPD), probing attachment level (PAL), and bleeding on probing (BOP) were recorded at baseline and at the 2nd, 4th, and 12th weeks. The levels of interleukin 1 beta (IL-1ß), transforming growth factor-beta (TGF-ß), tissue-type plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1) were also determined in the peri-implant crevicular fluid samples biochemically. RESULTS: The mSBI and t-PA at the 2nd week (p = 0.003; p = 0.003); the mPlI, mSBI, BOP, t-PA, and PAI-1 at the 4th week (p < 0.05; p < 0.001; p < 0.001; p = 0.015; p = 0.011); and the mPlI, mSBI, IL-1ß, t-PA, and PAI-1 at the 12th week (p < 0.05; p < 0.001; p = 0.013; p < 0.001; p = 0.002) were significantly lower in the OI group compared with those in the C group. Meanwhile, PAI-1 at the 2nd week, mSBI at the 4th week, and t-PA at the 12th week were significantly lower in the OI group compared with those in the IB group (p < 0.001; p = 0.011; p = 0.003). At the 2nd, 4th, and 12th weeks, all other parameters were not statistically different in the three groups. CONCLUSION: The clinical indexes (such as mSBI and BOP) that play an important role in the diagnosis of peri-implant mucositis showed the lowest means (although limited) in the OI group at all evaluation time points. Moreover, when the clinical and biochemistry results were interpreted altogether, it became apparent that the OI group exhibited similar or more effective results than the IB group in resolving peri-implant mucositis. In light of the foregoing, this study concluded that the use of an oral irrigator can be as effective as an interdental brush in interdental cleaning. CLINICAL RELEVANCE: In this study, it is suggested that the regular use of an oral irrigator along with a toothbrush could be an appropriate alternative to other oral hygiene products such as dental floss and interdental brush for the management of peri-implant mucositis by preventing the accumulation of dental plaque (NCT03844035).

Nonsurgical Periodontal Therapy Reduces Salivary and Gingival Crevicular Fluid YKL-40 and IL-6 Levels in Chronic Periodontitis.

PURPOSE: A novel acute-phase protein, YKL-40, is known as an inflammation-associated glycoprotein. YKL-40 is shown to be linked to inflammation, endothelial dysfunction and tissue remodeling secreted by various cells and is also considered to be stimulated by cytokines such as interleukin-6 (IL-6). The present study aimed to investigate YKL-40 and IL-6 levels in saliva and gingival crevicular fluid (GCF) of patients with chronic periodontitis (CP) after non-surgical periodontal therapy for the first time. MATERIALS AND METHODS: Twenty-six CP patients and 26 periodontally healthy individuals were enrolled. Clinical measurements were recorded; saliva and GCF samples were obtained at baseline and 1 and 3 months after non-surgical periodontal therapy. Levels of YKL-40 and IL-6 in saliva and GCF were analysed by ELISA. RESULTS: Salivary and GCF YKL-40 and IL-6 levels were found to be statistically significantly higher in CP patients compared to healthy controls at baseline (p < 0.001). At 1 and 3 months after the completion of treatment, both YKL-40 and IL-6 levels in saliva and GCF had statistically significantly decreased compared with baseline values in CP patients (p < 0.001). On the other hand, no statistically significant difference was observed between 1 and 3 months in terms of salivary and GCF YKL-40 and IL-6 levels or any of the clinical findings (p > 0.016). CONCLUSION: Salivary and GCF YKL-40 levels may be useful to evaluate resolution of periodontal inflammation. Within the limits of this study, YKL-40 acute-phase protein might be a potential biomarker for detection of periodontitis and monitoring the response to periodontal therapy.

Histopathological and biochemical evaluation of paeoniflorin administration in an experimental periodontitis model.

The purpose of this study was to evaluate the effects of administered Paeoniflorin (Pae) on periodontal tissues within an experimental periodontitis model. Forty male Wistar rats were used in this study and experimental periodontitis was created in all rats except in the control group (n = 10, first group). In the periodontitis group, experimental periodontitis was created but no other application was performed (n = 10, second group). In the other groups created experimental periodontitis, systemic Pae (n = 10, third group) or saline (n = 10, fourth group) was applied. A biochemical analysis of the gingival vascular endothelial growth factor (VEGF) levels and a histomorphometric analysis (measurements of the area of alveolar bone, alveolar bone resorption, and attachment loss) were performed. In the Pae group, the area of the alveolar bone was increased, while alveolar bone resorption and attachment loss decreased. Gingival VEGF levels increased in all groups that created experimental periodontitis and the greatest increase seen in the Pae group. Histomorphometric and biochemical analyses in this study suggest that Pae has a curative effect on periodontal tissues. However, additional studies are needed to confirm these results.

Assessment of MMP-1, MMP-8 and TIMP-2 in experimental periodontitis treated with kaempferol.

PURPOSE: The objective of this study was to investigate the effect of a dietary flavonoid, kaempferol, which has been shown to possess antiallergic, anti-inflammatory, anticarcinogenic, and antioxidant activities on the periodontium by histomorphometric analysis and on gingival tissue matrix metalloproteinase-1 (MMP-1), MMP-8, and tissue inhibitor of metalloproteinase-2 (TIMP-2) by biochemical analysis of rats after experimental periodontitis induction. METHODS: Sixty Wistar rats were randomly divided into six groups of ten rats each, and silk ligatures were placed around the cervical area of the mandibular first molars for 15 days, except in the healthy control rats. In the experimental periodontitis groups, systemic kaempferol (10 mg/kg/2d) and saline were administered by oral gavage at two different periods (with and without the presence of dental biofilm) to all rats except for the ten non-medicated rats. Alveolar bone area, alveolar bone level, and attachment level were determined by histomorphometric analysis, and gingival tissue levels of MMP-1, MMP-8, and TIMP-2 were detected by biochemical analysis. RESULTS: Significantly greater bone area and significantly less alveolar bone and attachment loss were observed in the kaempferol application groups compared to the control groups (P<0.05). In addition, gingival tissue MMP-1 and -8 levels were significantly lower in the kaempferol application groups compared to the control groups and the periodontitis group (P<0.001). There were no statistically significant differences in TIMP-2 levels between the kaempferol and saline application groups (P>0.05). CONCLUSIONS: Kaempferol application may be useful in decreasing alveolar bone resorption, attachment loss, and MMP-1 and -8 production in experimental periodontitis.

Analysis of YKL-40 acute-phase protein and interleukin-6 levels in periodontal disease.

BACKGROUND: YKL-40, a new acute-phase protein, is shown to be elevated in inflammatory diseases, such as rheumatoid arthritis, type 2 diabetes mellitus, and coronary artery diseases. However, there is no data indicating a relationship between YKL-40 and periodontal disease. Interleukin-6 (IL-6) is the major regulator of acute-phase protein synthesis and one of the most studied inflammatory markers in periodontal disease. The purpose of the present study is to evaluate YKL-40 and IL-6 levels in gingival crevicular fluid (GCF) and serum of patients with periodontal disease and healthy individuals. METHODS: Periodontally healthy individuals (n = 15), patients with gingivitis (n = 15), and patients with severe chronic periodontitis (CP) (n = 15) without any systemic disease were included in the study. Clinical measurements were recorded; GCF and blood samples were obtained from each participant. GCF and serum YKL-40 and IL-6 levels were analyzed by enzyme-linked immunosorbent assay. Statistical analysis was performed by parametric and non-parametric tests. RESULTS: Total amounts of YKL-40 and IL-6 in GCF as well as serum YKL-40 and IL-6 levels were significantly higher in patients with gingivitis and CP compared with healthy controls (P <0.01). YKL-40 levels in GCF and serum as well as serum IL-6 levels were significantly higher in patients with CP compared with patients with gingivitis (P <0.01). CONCLUSIONS: YKL-40 levels in GCF as well as serum YKL-40 and IL-6 levels increased from gingivitis to periodontitis. Within the limits of the present study, the YKL-40 molecule might be a potential novel inflammatory marker of periodontal disease.

Assessment of vascular endothelial growth factor and matrix metalloproteinase-9 in the periodontium of rats treated with atorvastatin.

BACKGROUND: The aim of this study is to examine, for the first time, the role of systemic and local atorvastatin application on periodontium using histomorphometric and immunohistochemical analysis during and after experimental periodontitis induction with or without the presence of microbial dental biofilm. METHODS: One hundred ten male Wistar rats were used. Silk ligatures were placed around the cervical area of the mandibular first molars; rats in the healthy control group received no ligatures (n = 10). In experimental periodontitis groups (n = 90), systemic and local atorvastatin and saline were administered in three different periods; the control periodontitis group (n = 10) received no treatment. Histomorphometric analysis, which included alveolar bone area, alveolar bone level, and attachment loss, and immunohistochemical analysis, which included immunoreactivity of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9, were performed after the rats were sacrificed at the end of the experimental procedure. RESULTS: There was a greater increase in alveolar bone area and VEGF immunoreactivity, as well as a greater decrease in alveolar bone and attachment loss and MMP-9 immunoreactivity, with systemic and local atorvastatin application during and after induction of experimental periodontitis. Local atorvastatin application showed better results on periodontium with regard to alveolar bone findings. CONCLUSIONS: Systemic and local atorvastatin application showed beneficial effects on periodontium during and after induction of experimental periodontitis. Within the limits of this study, it can be concluded that atorvastatin, which is used for hypercholesterolemia treatment, can also be used as a protective and therapeutic agent for periodontal disease.

Effects of tacrolimus and nifedipine, alone or in combination, on gingival tissues.

BACKGROUND: The aim of this study is to compare gingival changes induced by short- and long-term tacrolimus and nifedipine administration, alone or in combination, and evaluate the expression levels of tumor suppressor phosphatase and tensin homolog (PTEN) in drug-induced gingival overgrowth. METHODS: Eighty rats were equally divided into eight groups: 1) tacrolimus for 8 weeks; 2) nifedipine for 8 weeks; 3) tacrolimus and nifedipine for 8 weeks; 4) 8-week control; 5) tacrolimus for 24 weeks; 6) nifedipine for 24 weeks; 7) tacrolimus and nifedipine for 24 weeks; and 8) 24-week control. Histomorphometric analyses included measurements of epithelial thickness, connective tissue thickness, and height. Stereologic analyses included measurements of volumetric densities of fibroblasts (Vf), collagen fibers (Vcf), and blood vessels (Vbv). In addition, PTEN expression was analyzed using immunohistochemistry. RESULTS: Epithelial thickness and connective tissue thickness were significantly increased in groups 5, 6, and 7 compared to group 8 (P <0.05), whereas connective tissue height was significantly increased in groups 5 and 7 (P <0.001). Vf and Vcf were significantly increased in group 7 compared to group 8 (P <0.001). PTEN immunoreactivity was significantly decreased in all experimental groups compared to the control groups (P <0.05). CONCLUSIONS: Results suggest that duration of drug administration is a more important risk factor than drug combination. The results include a potentially new insight about PTEN's role in the etiology of drug-induced gingival overgrowth.

Comparison of mesenchymal stem cells and autogenous cortical bone graft in the treatment of class II furcation defects in dogs.

The purpose of this study was to compare the effectiveness of mesenchymal stem cells (MSCs) with platelet-rich plasma (PRP) as scaffold and autogenous cortical bone (ACB) graft with and without PRP in the regenerative treatment of class II furcation defects in dogs. The mandibular second, third, and fourth premolars (P2, P3, P4) and maxillary P3 and P4 of both sides in three dogs were selected for experimentation. Class II furcation defects (5 mm in height and 2 mm in depth) were surgically created. Five weeks after the first operation, scaling + root planning (group 1), PRP (group 2), ACB (group 3), combination of ACB/PRP (group 4), and combination of MSCs/PRP (group 5) treatments were performed during open flap debridement. The percentage of cementum and alveolar bone formation was evaluated by histomorphometric analysis after a healing period of 8 weeks. There was new cementum along with periodontal ligament and coronal growth of alveolar bone in all groups. Cementum formation was significantly higher in groups 3, 4, and 5 compared to the control group (P < 0.05) with no significant difference between groups 2, 3, 4, and 5. Alveolar bone formation was similar in all groups (P > 0.05). It can be concluded that periodontal regeneration with complete filling of class II furcation defects with cementum, alveolar bone, and periodontal ligament is obtained 8 weeks after ACB, ACB/PRP, and MSCs/PRP treatments; however, efficacy of none is higher than another.

Vascular endothelial growth factor expression levels of gingiva in gingivitis and periodontitis patients with/without diabetes mellitus.

OBJECTIVE AND DESIGN: The aim of this study was to determine vascular endothelial growth factor (VEGF) mRNA expression levels in gingival tissues of gingivitis and periodontitis patients with diabetes mellitus and those without. The hypothesis tested is that expression of VEGF, considered the effective cytokine in the relationship between diabetes and periodontal disease, is differentially affected in gingivitis and periodontitis patients with or without diabetes mellitus compared to healthy controls. METHODS: Forty-five subjects were evaluated in five groups; individuals with gingivitis (group 1; n = 10), individuals with periodontitis (group 2; n = 10), individuals with gingivitis + type II diabetes (group 3; n = 10), individuals with periodontitis + type II diabetes (group 4; n = 10), and individuals without periodontal and systemic disease (group 5; n = 5). VEGF mRNA levels in gingival tissues were measured by quantitative real-time PCR using Lightcycler. RESULTS: Expression of VEGF mRNA was detected in all groups. There was no significant difference in expression levels of VEGF mRNA between groups (P > 0.05). CONCLUSIONS: VEGF expression is probably related to both maintenance of periodontal health and periodontal tissue destruction. It can be concluded that systemic condition in type II diabetes mellitus under good metabolic control does not seem to have additional effects on gingival tissue VEGF mRNA levels in gingivitis and periodontitis patients.

Influence of different suturing techniques on periodontal health of the adjacent second molars after extraction of impacted mandibular third molars.

OBJECTIVE: The objective of this randomized controlled trial was to compare the effects of different suturing techniques (simple loop suture vs. anchor suture) on the periodontal health of the adjacent second molars after impacted mandibular third molar extraction. STUDY DESIGN: Fifteen patients with bilaterally identical impacted mandibular third molars were used. Using split-mouth design, flaps were closed with either anchor suture technique or simple loop suture technique after the extraction of third molars. Postoperative examination included probing pocket depth (PPD) and clinical attachment level (CAL) measured at the distal surface of the second molars before surgery and 6 months after surgery. RESULTS: The PPD and CAL in the distal surfaces of the second molars were significantly higher after 6 months in the simple suture group (P = .001), whereas no differences were found in the anchor suture group (P > .05). Intergroup comparisons showed that the 6-month PPD and CAL values of the distal surfaces were significantly higher in the simple suture group compared with the anchor suture group (P = .015). CONCLUSION: The results suggest that anchor suture might be a better technique to use to maintain healthy periodontium and to prevent periodontal problems after the extraction of impacted third molars.

Effects of risedronate on alveolar bone loss and angiogenesis: a stereologic study in rats.

BACKGROUND: The present study was designed to evaluate the effects of risedronate, one of the most potent bisphosphonates, on alveolar bone resorption and angiogenesis in rats with experimental periodontitis to identify dose-response curves and treatment durations that can be therapeutic for periodontal therapy versus those associated with osteonecrosis of the jaws. METHODS: Thirty-five rats, 25 with experimental periodontitis (groups 1 through 5) and 10 with healthy periodontium (groups 6 and 7), were divided into seven equal groups: group 1 received no treatment; groups 2 and 3 received risedronate, 0.1 and 1 mg/kg, respectively, for 3 weeks; groups 4 and 5 received risedronate, 0.1 and 1 mg/kg, respectively, for 8 weeks; and groups 6 and 7 received 0.9% NaCl for 3 and 8 weeks, respectively. Animals in groups 2 through 7 were administered treatment 5 days per week. After histologic processing, histomorphometric and stereologic analyses were carried out to estimate the number of blood vessels (NBV) and the volumetric densities of bone (Vb), marrow (Vm), osteoblasts (Vob), and osteoclasts (Voc). RESULTS: A total of 0.1 and 1 mg/kg risedronate for 3 weeks (groups 2 and 3) significantly increased Vb and Vob and decreased Vm more prominently in group 2 (P <0.001), whereas 1 mg/kg risedronate for 8 weeks (group 5) induced no significant improvement in these parameters compared to group 1 (P >0.05). No significant decrease in Voc was found in drug-administered groups compared to group 1 (P >0.05). A significant decrease in NBV (P <0.01) and positive correlation between NBV and Vb (r(2) = 0.941; P = 0.006) were found only in group 5. CONCLUSION: A short duration of risedronate administration may be useful in inhibiting bone resorption in periodontitis, whereas excessive dosages of the drug administered in longer durations can lead to impairment of bone formation and angiogenesis.

The expression of vascular endothelial growth factor in a rat model at destruction and healing stages of periodontal disease.

BACKGROUND: The major role of vascular endothelial growth factor (VEGF), an angiogenic mediator, in promoting the progression or the healing of periodontal disease is still unclear. The aim of this study was to evaluate the VEGF expression in the destruction and healing stages of periodontal disease and to investigate the association between VEGF expression and vascularization with regard to the number and diameters of blood vessels. METHODS: Thirty rats were distributed equally into two test groups and a control group. Experimental periodontal disease was induced in the test groups by silk ligatures, which were kept in position for 40 days. On the 40th day, ligatures were removed from the healing group, whereas ligatures were left in position in the destruction group. On the 60th day, rats were sacrificed; histomorphometric and biochemical analyses were carried out to determine the number and diameters of blood vessels and the assessment of VEGF concentration by enzyme-linked immunosorbent assay, respectively. RESULTS: There was a statistically significant increase in the number of blood vessels in the healing group and in the diameters of blood vessels in the destruction group compared to the control group (P <0.001). In vivo VEGF expressions were highest in the healing group (P <0.001) and correlated significantly with the number of blood vessels (r(2) = 0.814; P = 0.001). CONCLUSION: VEGF expression may be related more to the healing stage of periodontal disease than to the destruction stage of the lesion.

Levels of gingival tissue platelet activating factor after conventional and regenerative periodontal surgery.

The hypothesis, a relationship between gingival tissue platelet activating factor (PAF) levels and healing after periodontal surgery, was tested by measuring PAF levels in gingival tissues collected from sites that had undergone flap surgery and guided tissue regeneration (GTR) or flap surgery alone. Using a split-mouth design, 20 intrabony defects were randomly assigned to treatment with flap surgery and GTR (group 1) or with flap surgery alone (group 2). Gingival tissue samples were obtained at surgery (baseline) and at 6-month follow-up evaluation visit. One half of each sample was used for analysis of PAF levels by high-performance liquid chromatography, and the other half of the sample was used for histomorphometric analysis that included measurements of number and diameter of blood vessels. PAF levels and diameter of blood vessels were significantly decreased (p < 0.01), and the number of blood vessels was significantly increased (p < 0.05) in both groups after 6 months compared to the baseline values. Postoperative number of blood vessels were significantly higher in group 1 (p < 0.05), whereas there was no significant difference in postoperative PAF levels between the two groups (p > 0.05). Based on the reported results, it is suggested that a decrease in gingival PAF levels might be found after conventional and regenerative periodontal surgery.

Comparison of the proliferative activity in gingival epithelium after surgical treatments of intrabony defects with bioactive glass and bioabsorbable membrane.

Guided tissue regeneration is based on preventing the more rapidly proliferating epithelium from growing into the periodontal defect after surgical procedures incorporating barrier membranes. The aim of this study was to compare the proliferative activity of gingival epithelium using proliferating cell nuclear antigen (PCNA) as a marker of cell proliferation after surgical treatments with bioactive glass graft material and bioabsorbable membrane. Using split mouth design, 20 intrabony defects were randomly assigned treatments with bioactive glass (BG group) or bioabsorbable membrane (BM group). Gingival biopsies were taken at preoperative and postoperative 12 weeks. After histological processing, the number of the inflammatory cells was measured in hematoxylin and eosin-stained sections; PCNA expression was determined in immunohistochemically-stained sections. At postoperative 12 weeks, the number of the inflammatory cells was significantly decreased (p < 0.01), PCNA expression was significantly increased (p < 0.001) in both treatment groups compared to baseline data. There was no significant difference in PCNA expression between baseline values of two groups (p > 0.05), while at postoperative 12 weeks, increase in BG group was significantly greater than that in BM group (p < 0.001). These results suggest that epithelial cell proliferation is more prominent after treatment of intrabony defects with bioactive glass compared to the treatment with bioabsorbable membrane.

Increased expression of vascular endothelial growth factor in cyclosporin A-induced gingival overgrowth in rats.

BACKGROUND: Gingival overgrowth is a side effect associated with cyclosporin A (CsA) therapy. The lesion is characterized by increased epithelial thickness, enlargement of connective tissue, and increased vascularization. The aim of this experimental study was to examine the role of vascular endothelial growth factor (VEGF) in the pathogenesis of CsA-induced gingival overgrowth. METHODS: Twenty male Wistar rats were divided into two groups of 10 animals each. For the development of gingival overgrowth, one group received CsA therapy subcutaneously in a daily dose of 10 mg/kg for 60 days, and the other group was used as a control. At the end of the experimental period, rats were subsequently decapitated, and the mandibles with the surrounding gingiva and soft tissue were removed. Half of each sample was used for histomorphometric analysis, and the other half was used for biochemical analysis. Histomorphometric analysis included the measurements of the number and diameter of blood vessel profiles under a microscope, and biochemical analysis included the assessment of VEGF concentration by enzyme-linked immunosorbent assay (ELISA). RESULTS: The histomorphometric findings showed that the number of blood vessel profiles increased in the CsA group compared to the control group (P <0.001), although the increase in the diameter of blood vessel profiles was not significant (P >0.05). The biochemical findings showed that in vivo VEGF expression was higher in the CsA group compared to the control group (P <0.001). CONCLUSION: The results of this study suggest that increased VEGF expression may be associated with the pathogenesis of CsA-induced gingival overgrowth.