Effects of rosuvastatin on inducible nitric oxide synthase in rats with hyperlipidaemia and periodontitis.

BACKGROUND AND OBJECTIVE: Nitric oxide is a free radical that is synthesized from l-arginine by nitric oxide synthase (NOS). The level of inducible NOS (iNOS) in gingiva with periodontitis is higher than that in healthy gingiva. The aim of this study was to evaluate the effects of rosuvastatin administration on alveolar bone loss (ABL) and iNOS(+) cell counts in gingival tissues in rats with ligature-induced experimental periodontitis with/without hyperlipidaemia. MATERIAL AND METHODS: The rats were randomly divided into seven groups: Hy (cholesterol-added diet/water administration); HyP (cholesterol-added diet/periodontitis/water administration); HyPR (cholesterol-added diet/periodontitis/rosuvastatin administration); P (standard diet/periodontitis/water administration); PR (standard diet/periodontitis/rosuvastatin administration); C (standard diet/water administration); and R (standard diet/rosuvastatin administration). Experimental periodontitis was induced with silk ligatures, and rosuvastatin/water was administered to rats by oral gavage for the last 2 weeks of the 8-week study. After the rats were killed in week 8, histomorphometric and histological analyses were performed. Immunostained iNOS(+) cells were counted in the gingival samples and the Mann-Whitney U-test was used for statistical analysis. RESULTS: The experimental groups exhibited increases in total cholesterol and low-density lipoprotein, except for Groups C and R. The cholesterol-added diet induced ABL in Group Hy. Of the periodontitis groups, the lowest ABL was found in Group PR. While there was a significant difference in ABL between Groups P (0.82 ± 0.15 mm) and PR (0.70 ± 0.21 mm) receiving a standard diet (P < .05), no difference was observed between Groups HyP (0.77 ± 0.07 mm) and HyPR (0.76 ± 0.11 mm) receiving a cholesterol-added diet (P Ëƒ .05). Rosuvastatin significantly reduced expression of iNOS in Groups PR (18.40 ± 2.31%) and HyPR (24.00 ± 4.83%) compared with Group P (30.90 ± 2.42%; P < .001). However, a larger number of iNOS(+) cells was found in Group HyPR than in Group PR (P < .001). CONCLUSION: Administration of rosuvastatin reduced gingival iNOS expression in ligature-induced periodontitis with/without hyperlipidaemia. It also led to significant differences in ABL in rats with periodontitis, except when periodontitis was associated with hyperlipidaemia. These findings could provide an important contribution in further studies to evaluate the role of rosuvastatin as a host modulatory agent in the pathogenesis of periodontal diseases.

R202Q/M694V as novel MEFV gene mutations in chronic periodontitis and familial Mediterranean fever.

BACKGROUND AND OBJECTIVE: Familial Mediterranean fever (FMF) and chronic periodontitis are inflammatory diseases leading to an increase in the number of inflammasomes. To date, no published studies have reported on mutations in the Mediterranean fever (MEFV) gene in patients with chronic periodontitis, although the roles of MEFV gene mutations in FMF and FMF-associated amyloidosis (FMF-A) are well known. Therefore, the aim of this study was to evaluate the frequencies of MEFV gene mutations and serum amyloid A (SAA) and high-sensitivity C-reactive protein (hs-CRP) levels in patients with chronic periodontitis, FMF and FMF-A. MATERIAL AND METHODS: The study population included 122 patients with FMF and 128 subjects who were systemically healthy. Clinical periodontal parameters, including the plaque index, gingival index, probing pocket depth, clinical attachment level and percentage of bleeding on probing were recorded. Blood samples were obtained from patients with FMF and systemically healthy controls, and all mutations located on exons 2 and 10 of the MEFV gene were analyzed by DNA Sanger Sequencing, which is the gold standard. SAA and high-sensitive CRP levels were also assessed. RESULTS: Mean gingival index, percentage of bleeding on probing, probing pocket depth and clinical attachment level, and the levels of SAA and hs-CRP were higher in the FMF-A group than those in the FMF and control groups. The two most relevant mutations in patients with FMF were heterozygous M694V (46.2%), and heterozygous R202Q (32.7%). The frequencies of the homozygous M694V and R202Q mutations in the FMF-A group were 53.8% and 46.1%, respectively. The complex R202Q/M694V homozygous state led to an increased risk of chronic periodontitis (odds ratio: 3.6), and FMF-A (odds ratio: 7.6). CONCLUSION: This is the first study to report the R202Q mutation in patients with periodontitis. Furthermore, the MEFV gene-mediated inflammatory pathway increased serum acute phase reactants, and the changes in the R202Q and M694V could play a role in inflammatory-genetic diseases, such as FMF, FMF-associated amyloidosis and chronic periodontitis.

Gingival crevicular fluid tissue/blood vessel-type plasminogen activator and plasminogen activator inhibitor-2 levels in patients with rheumatoid arthritis: effects of nonsurgical periodontal therapy.

BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the effect of nonsurgical periodontal therapy on clinical parameters and gingival crevicular fluid levels of tissue/blood vessel-type plasminogen activator (t-PA) and plasminogen activator inhibitor-2 (PAI-2) in patients with periodontitis, with or without rheumatoid arthritis (RA). MATERIAL AND METHODS: Fifteen patients with RA and chronic periodontitis (RA-P), 15 systemically healthy patients with chronic periodontitis (H-P) and 15 periodontally and systemically healthy volunteers (C) were included in the study. Plaque index, gingival index, probing pocket depth, clinical attachment level, bleeding on probing, gingival crevicular fluid t-PA and PAI-2 levels, erythrocyte sedimentation rate, serum C-reactive protein and disease activity score were evaluated at baseline and 3 mo after mechanical nonsurgical periodontal therapy. RESULTS: All periodontal clinical parameters were significantly higher in the RA-P and H-P groups compared with the C group (p < 0.001) and decreased significantly after treatment (p < 0.001). Pretreatment t-PA levels were highest in the RA-P group and significantly decreased post-treatment (p = 0.047). Pre- and post-treatment PAI-2 levels were significantly lower in controls compared with both periodontitis groups (p < 0.05). Gingival crevicular fluid volume and the levels of t-PA and PAI-2 were significantly correlated. CONCLUSION: In patients with periodontitis and RA, nonsurgical periodontal therapy reduced the pretreatment gingival crevicular fluid t-PA levels, which were significantly correlated with gingival crevicular fluid PAI-2 levels. The significantly higher t-PA and PAI-2 gingival crevicular fluid levels in periodontal patients, regardless of systemic status, suggest that the plasminogen activating system plays a role in the disease process of periodontitis.

The effects of periodontal therapy on gingival crevicular fluid matrix metalloproteinase-8, interleukin-6 and prostaglandin E2 levels in patients with rheumatoid arthritis.

OBJECTIVE: The aim of this study was to evaluate the effects of non-surgical periodontal therapy on gingival crevicular fluid levels of matrix metalloproteinase-8 (MMP-8), interleukin-6 (IL-6) and prostaglandin E2 (PGE2 ) in patients with rheumatoid arthritis (RA) with periodontal disease. MATERIAL AND METHODS: Twenty-seven patients with gingivitis and periodontitis with RA, 26 patients with gingivitis and periodontitis that were systemically healthy and 13 periodontally and systemically healthy volunteers (control group) were included in this study. RA activity was assessed by disease activity score test. The clinical periodontal parameters, fasting venous blood and gingival crevicular fluid samples were obtained and gingival crevicular fluid MMP-8, IL-6 and PGE2 levels were evaluated at baseline and at 3 mo follow-up after non-surgical periodontal treatment. RESULTS: Gingival crevicular fluid MMP-8, PGE2 and IL-6 levels were higher in all groups than the control group. Following periodontal therapy, there were significant decreases in gingival crevicular fluid MMP-8, PGE2 and IL-6 levels from patients with RA with periodontitis (p < 0.05). Plaque index, gingival index and bleeding on probing were significantly correlated with IL-6 and PGE2 at baseline and at 3 mo follow-up after non-surgical periodontal treatment. CONCLUSION: Non-surgical periodontal therapy of patients with RA with periodontitis may provide beneficial effects on local inflammatory control via decreases in gingival crevicular fluid MMP-8, PGE2 and IL-6 levels.

Comparison of bone mineral density in the jaws of patients with and without chronic periodontitis.

OBJECTIVES: Although several studies have addressed the relationship between systemic bone mineral status and the severity of periodontitis, there is little knowledge of the relationship between periodontal disease and locally detected bone mineral density. The aim of this study was to compare the mandibular bone mineral density of patients with chronic periodontitis with that of periodontally healthy subjects. METHODS: 48 systemically healthy subjects were included in the study and underwent a periodontal examination to determine their status. 24 subjects were periodontally healthy and the other 24 had moderate or severe chronic periodontitis. The mandibular bone mineral density of the subjects was determined by dual energy X-ray absorptiometry. The region of interest on the body of the mandible was independently determined on the dual energy absorptiometry radiographs, and a computer calculated the bone mineral density of these regions. RESULTS: The mandibular bone mineral density of the subjects with periodontitis was significantly lower than that of the periodontally healthy subjects (p < 0.01). There were significant negative correlations between the mandibular bone mineral density values and parameters related to the amount of periodontal destruction. CONCLUSIONS: Low bone mineral density in the jaw may be associated with chronic periodontitis.

Proinflammatory cytokine levels in hyperlipidemic patients with periodontitis after periodontal treatment.

OBJECTIVE: The aim of this study was to evaluate the effects of periodontal treatment on serum and gingival crevicular fluid (GCF) proinflammatory cytokine levels in hyperlipidemic patients with periodontitis. MATERIALS AND METHODS: Fifty-two patients with hyperlipidemia and periodontitis and 28 systemically healthy controls with periodontitis (C) were included in the study. Hyperlipidemic groups were divided into two groups as suggested diet (HD) and prescribed statin (HS). The clinical periodontal parameters, fasting venous blood, and GCF samples were obtained, and serum tumor necrosis factor-alpha (TNF-α), interleukin (IL) 1-beta, and IL-6 levels were evaluated at baseline and at 3 months follow-up (3MFU) after the completion of the non-surgical periodontal treatment that included scaling and root planning. RESULTS: Percentage of bleeding on probing was significantly higher in the HS group than both the HD and C groups. In the HD and HS groups, there were significant decreases in serum IL-6 and GCF TNF-α levels between the 3MFU and baseline. A significant decrease was also found in GCF IL-6 at the end of the study period in the HS group. CONCLUSION: The combination of the periodontal therapy and antilipemic treatment may provide beneficial effects on the metabolic and inflammatory control of hyperlipidemia.

Short-term effects of periodontal therapy as an adjunct to anti-lipemic treatment.

OBJECTIVE: This study was conducted to assess the effect of improved periodontal health following periodontal treatment on metabolic lipid control of patients on anti-lipemic treatment. MATERIALS AND METHODS: The study population consisted of 20 patients aged 34-62 years with diagnoses of hyperlipidemia and chronic periodontitis. All patients used statin to treat their elevated levels of low-density lipoprotein cholesterol. Blood samples were obtained for measurement of serum lipids, fasting plasma glucose, and high sensitive C-reactive protein. Periodontal parameters, including plaque index, gingival index, probing pocket depth, clinical attachment level, and percentage of bleeding on probing, were evaluated. All parameters were assessed in each subject at baseline, after 3 months as a control (at the time of periodontal treatment), and 3 months after the non-surgical periodontal treatment that included scaling and root planning. RESULTS: All lipid parameters decreased after the periodontal treatment, but only the decreases in total cholesterol and low-density lipoprotein cholesterol levels reached statistical significance compared to baseline (P = 0.002 and P = 0.003, respectively). CONCLUSION: Improved periodontal health may influence metabolic control of hyperlipidemia and could be considered as an adjunct to the standard measures of hyperlipidemic patient care.