dinoprost and Periodontitis

The purpose of the present study was to evaluate the effect of a relatively selective cyclooxygenase (COX)-2 inhibitor (nimesulide) and non-selective COX-1/COX-2 inhibitor (naproxen) used as an adjunct to non-surgical (scaling and root planing [SRP]) periodontal therapy in chronic periodontitis patients on the gingival tissue (GT) levels of prostaglandin (PG)E2 and PGF2alpha.. Thirty patients with chronic periodontitis were divided into 3 groups of 10 each. One group received 100 mg of nimesulide; one received 275 mg of naproxen sodium; and the third group received placebo tablets in a 2 x 1 regimen for 10 days as an adjunct to SRP. GT samples were obtained before drug intake and on day 10. Plaque index (PI) and papillary bleeding index (PBI) scores were recorded at baseline, day 10, and at 3 months; probing depth (PD) and clinical attachment level (CAL) were recorded at baseline and at 3 months. The levels of PGE2 were detected using an enzyme immunoassay (EIA), and the levels of PGF2alpha were analyzed by radioimmunoassay (RIA). Differences among and within the groups were assessed using non-parametric statistical analysis. Ten periodontally healthy individuals served as controls.. All 3 groups showed statistically significant reductions in PBI and PI on day 10 and at 3 months (P < 0.02), and in PD and CAL at 3 months (P < 0.02, P < 0.05, respectively). In the naproxen group, GT PGE2 levels exhibited a significant decrease (P < 0.05). However, the decrease of GT PGE2 levels in the nimesulide group was insignificant (P > 0.05), while a significant increase was observed in the placebo group (P < 0.05) on day 10. Both the nimesulide and naproxen groups showed a significant decrease (P<0.05) in PGF2alpha level, while the placebo group showed a significant increase (P<0.05).. Nimesulides, relatively selective COX-2 inhibitors, may have additional inhibitory effects on GT PGF2alpha levels in the first week following non-surgical periodontal treatment. However, nimesulide has an insignificant effect on reducing PGE2 levels in gingival tissue. The determination of GT levels of COX-1 and COX-2 enzymes as well as PGE2 and PGF2alpha in long-term studies may provide further support for the adjunctive use of selective COX-2 inhibitors in treatment of chronic periodontitis.

Topics: Adult; Chronic Disease; Cyclooxygenase 1; Cyclooxygenase Inhibitors; Dental Plaque Index; Dental Scaling; Dinoprost; Dinoprostone; Double-Blind Method; Female; Follow-Up Studies; Gingiva; Humans; Isoenzymes; Male; Matched-Pair Analysis; Membrane Proteins; Middle Aged; Naproxen; Periodontal Attachment Loss; Periodontal Index; Periodontal Pocket; Periodontitis; Placebos; Prostaglandin-Endoperoxide Synthases; Root Planing; Statistics as Topic; Statistics, Nonparametric; Sulfonamides

In a previous report, we demonstrated the inverse association of high serum 8-isoprostane levels, a marker for oxidative stress, with decreased serum IgG antibodies to oral bacteria. The association between increased serum IgG with increased plaque and periodontitis (increased probing depths) was attenuated by high systemic oxidative stress. Other investigations have reported a role for systemic oxidative stress as a stimulus of hepatic C-reactive protein (CRP) response. These observations led us to hypothesize that the reported relationship of periodontitis to elevated serum CRP, a systemic inflammatory marker, may be modified by oxidative stress and that the levels of serum antibodies to oral bacteria might be an intermediary explanatory variable linking the association of systemic oxidative stress, periodontal disease, and levels of CRP. This hypothesis was explored as a secondary analysis of the Dental ARIC (Atherosclerosis Risk in Communities) study using serum levels of CRP, serum IgG levels to 16 oral organisms, serum levels of 8-isoprostane, and periodontal status. The findings indicate periodontitis is associated with high CRP in the presence of elevated oxidative stress that serves to suppress the IgG response. Only within the highest 8-isoprostane quartile was periodontitis (pocket depth) associated with increased serum CRP levels (P = 0.0003). Increased serum IgG antibody levels to oral bacteria were associated with lowered serum CRP levels. Thus, systemic oxidative stress, which has been demonstrated to be associated with increased levels of CRP in other studies, appears to be associated with the suppression of bacterial-specific IgG levels, which in the presence of periodontal disease can result in an enhanced systemic CRP response. Conversely, individuals with increased serum IgG antibodies to plaque bacteria exhibit lowered serum CRP levels. These 2 factors, oxidative stress and the serum IgG response, appear to function in opposing directions to modify serum levels of CRP and the association with periodontitis.

Topics: Biofilms; C-Reactive Protein; Dinoprost; Female; Humans; Immunoglobulin G; Male; Middle Aged; Mouth; Oxidative Stress; Periodontitis; Prospective Studies

This study examined the reliability of assessing clinical periodontal measures on third molars, and the association between oral inflammation with periodontal pathology including third molars, and systemic inflammation including negative obstetric outcomes.. Reliability of third molar probing depth (PD) was assessed for 41 patients by trained examiners. The data for the association between oral inflammation with periodontal pathology and systemic outcomes were derived from an IRB-approved study, "Oral Conditions and Pregnancy." Full mouth periodontal exams including third molars were conducted at less than 24 weeks of pregnancy. Periodontal status, moderate/severe periodontal disease (15 or more sites PD > or =4 mm) was considered as a possible predictor of systemic inflammation and pre-term birth. The upper quartile of the extent of PD for third molars alone (PD > or =4 mm) also was considered as a possible exposure variable for the same outcomes. Chi-square and t tests were used to determine statistical significance (0.05). Significant predictor variables were included in multivariate models. Unconditional logistic multivariate models were used to derive odds ratios (OR) and 95% confidence intervals (CI).. Reliability of PD within 1 mm was excellent, and similar for third molars and non-third molars. Data from 1,020 obstetric patients were available for analysis. Eighteen percent of the patients delivered preterm, at less than 37 weeks. Having moderate/severe periodontal disease excluding third molars, was significantly associated with preterm birth (P = .008). Results were more significant if third molars were included (P = .0005). With multivariate models moderate/severe periodontal disease at enrollment including third molar PD, was associated with preterm birth (OR, 1.7; 95% CI, 1.1, 2.6). If only the extent of third molar PD was considered, odds also were increased for preterm birth (OR, 2.4; 95% CI, 1.1, 5.2). If only the extent of third molar PD was considered at enrollment, odds were increased for serum markers of systemic inflammation, elevated serum CRP, and oxidative stress, 8-isoPGF(2alpha).. Dental examiners could reliably assess clinical periodontal measures on third molars. Third molars should be included in studies of systemic outcomes associated with oral inflammation. Women of child-bearing age should be made aware of the systemic risks of oral inflammation with third molar periodontal pathology.

Topics: Adult; C-Reactive Protein; Dinoprost; Female; Humans; Logistic Models; Molar, Third; Odds Ratio; Periodontitis; Pregnancy; Premature Birth; Reproducibility of Results

Isoprostanes (IPs) are indicators of in-vivo oxidative stress, and have been successfully used as markers for chronic inflammatory processes. The presence of chronic periodontal disease and cigarette smoking has been individually linked to the development of atherosclerosis, yet data regarding oxidative stress in this context are not available yet. The aim of this study was to evaluate levels of the salivary prostaglandins (PGs) 8-epi-PGF(2alpha), 6-oxo-PGF(1alpha), thromboxane B(2) (TXB(2)) and PGF(2alpha) in association with periodontal disease status with and without additional cigarette smoking. We analyzed saliva samples from 121 adults, (aged 21-73 years, 90 non-smokers, 31 smokers) for levels of 8-epi-PGF(2alpha), 6-oxo-PGF(1alpha), TXB(2) and PGF(2alpha). On the basis of periodontal disease indices the periodontal status of each subject was assessed and outcomes were then correlated with smoking status and laboratory findings. Salivary 8-epi-PGF(2alpha) levels increased with deteriorating plaque index, and were significantly higher (115.5 +/- 23.5 pg/ml) in smoking individuals, when compared to non-smokers (70.2 +/- 20.4 pg/ml, p<0.0001). In addition, smokers showed higher TXB(2) and PGF(2alphas) and lower 6-oxo-PGF(1alpha) levels p<0.0001). Oxidative stress, as reflected by elevated salivary 8-epi-PGF(2alpha) levels, is associated with the extent of periodontal disease and is significantly aggravated by concomitant tobacco abuse. Chronic inflammation and smoking have been individually associated with the development of atherosclerosis. The results of this study indicate that: 1) salivary IPs can reliably assess the degree of oxidative stress, and: 2) smoking and periodontal disease are two modifiable cardiovascular risk factors, able to potentiate each other.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Dinoprost; Female; Humans; Isoprostanes; Male; Middle Aged; Multivariate Analysis; Oxidation-Reduction; Oxidative Stress; Periodontitis; Saliva; Smoking; Thromboxane B2

The present study was planned to evaluate the individual and combined effects of selective cyclooxygenase-2 (COX-2) inhibitor, celecoxib, and omega-3 fatty acid on the gingival tissue levels of prostaglandin E2 (PGE2), prostaglandin F2alpha (PGF2alpha), leukotriene B4 (LTB4), and platelet activating factor (PAF) in endotoxin-induced periodontitis in rats.. Experimental periodontitis was induced by repeated injection of Escherichia coli endotoxin (LPS). Forty-four adult male Sprague-Dawley rats were divided into five study groups: saline control, LPS, celecoxib, omega-3 fatty acid, and combination celecoxib and omega-3 fatty acid. Celecoxib and omega-3 fatty acid were given either as a single agent or as a combination therapy during 14 days of the study period. At the end of the 2-week protocol, the rats were sacrificed, the gingival tissues were dissected and extracted, and the extracts were analyzed for PGE2, PGF2alpha, and LTB4 levels by enzyme immunoassay and for PAF levels by radioimmunoassay. The defleshed jaws were analyzed morphometrically for alveolar bone loss. Data were evaluated statistically by using parametric tests.. LPS injection resulted in significantly more bone loss than the saline controls (P<0.05) and significant elevations in the gingival tissue levels of all the analyzed mediators except PGF2alpha. Individual administration of celecoxib revealed significant reductions in PGE2 and PAF levels (P <0.05), while omega-3 fatty acid provided significant reduction in PGE2, PGF2alpha, and LTB4 levels compared to the LPS group (P <0.05). Combined administration of celecoxib and omega-3 fatty acid exhibited significantly lower values than those of the LPS group in all the analyzed membrane phospholipid mediators (P <0.05), which approximated the levels in the saline control group (P>0.05).. The results of the present study indicate that celecoxib and omega-3 fatty acid, when used individually, show a rather partial effect on the control of the analyzed mediators, but when combined they show a synergic effect and provide significant reductions in the gingival tissue levels of PGE2, PGF2alpha, LTB4, and PAF in LPS-induced experimental periodontitis. These findings may pioneer further clinical human studies investigating the possible place of celecoxib and omega-3 fatty acid in periodontal treatment.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Celecoxib; Cyclooxygenase Inhibitors; Dinoprost; Dinoprostone; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Endotoxins; Fatty Acids, Omega-3; Leukotriene B4; Male; Periodontitis; Platelet Activating Factor; Pyrazoles; Rats; Rats, Sprague-Dawley; Sulfonamides

Doxycycline has been widely used in periodontal treatment for its antimicrobial and anti-enzymatic effects. Recently, bisphosphonates have been shown to inhibit alveolar bone resorption. The aim of the present study was to evaluate the effects of doxycycline and the bisphosphonate alendronate on the gingival tissue levels of prostaglandin E2 (PGE2), prostaglandin F2alpha (PGF2alpha), leukotriene B4 (LTB4), and platelet-activating factor (PAF) in endotoxin-induced periodontal breakdown in rats.. Experimental periodontitis was induced by repeated injection of Escherichia coli endotoxin (LPS) and 44 adult male Sprague-Dawley rats were divided into five study groups as follows: LPS, doxycycline + LPS, alendronate + LPS, doxycycline + alendronate + LPS, and saline control. Doxycycline and alendronate were given either as a single agent or as a combination therapy during the 7-day study period. At the end of the 1-week protocol, the rats were sacrificed, the gingival tissues were dissected and extracted, and the extracts were analyzed for PGE2, PGF2alpha, LTB4, and PAF levels. The defleshed jaws were analyzed morphometrically for alveolar bone loss. Data were evaluated statistically by using parametric tests.. Alveolar bone loss measurements revealed significantly higher values in LPS, doxycycline + LPS, alendronate + LPS, and doxycycline + alendronate + LPS groups in comparison to the saline control group (P <0.05). Combined administration of doxycycline and alendronate exhibited the most prominent inhibition on gingival tissue levels of PGE2 and PGF2alpha (P<0.05). Doxycycline + alendronate + LPS group also significantly reduced LTB4 and PAF levels, although doxycycline provided the most reduction in the levels of these mediators (P <0.05).. Alendronate and/or doxycycline may provide significant inhibition of the major inflammatory mediators of periodontal tissue destruction, and combined administration of these agents may provide beneficial effects in periodontal treatment. However, this hypothesis must be further verified by clinical human trials before introducing its use in dental practice.

Topics: Alendronate; Alveolar Bone Loss; Animals; Anti-Bacterial Agents; Dinoprost; Dinoprostone; Doxycycline; Drug Therapy, Combination; Endotoxins; Gingiva; Leukotriene B4; Male; Periodontitis; Platelet Activating Factor; Rats; Rats, Sprague-Dawley

The aim of the present study was 1) to evaluate the possible effects of therapeutic usage of omega-3 fatty acid on the gingival tissue levels of prostaglandin E2 (PGE2), prostaglandin F2alpha (PGF2alpha), platelet activating factor (PAF), and leukotriene B4 (LTB4) in endotoxin-induced periodontitis in rats and 2) to investigate whether prophylactic usage provides any additional benefits to therapeutic doses of omega-3 fatty acid.. Experimental periodontitis was induced by repeated injection of Escherichia coli lipopolysaccharide (LPS). Thirty-six adult male Sprague-Dawley rats were divided into four study groups: 1) saline controls; 2) LPS; 3) therapeutic omega-3 fatty acid (TO3); and 4) prophylactic plus therapeutic omega-3 fatty acid (P + TO3) groups. In TO3 group, omega-3 fatty acid was given for 15 days following induction of experimental periodontitis. In P + TO3 group, omega-3 fatty acid was started 15 days before baseline, and then periodontitis was induced at baseline and omega-3 fatty acid was continued for 15 days after baseline. On day 15 after baseline, all rats were anesthetized and sacrificed. PGE2, PGF2alpha, and LTB4 levels in gingival tissue samples were analyzed by enzyme immunoassay and PAF levels were analyzed by radioimmonoassay. Data were evaluated statistically by using parametric tests.. LPS injection resulted in significant amount of bone loss (P<0.05). Neither therapeutic nor prophylactic plus therapeutic administration of omega-3 fatty acid with the doses and duration of therapy used in the present study was effective in preventing endotoxin-induced alveolar bone loss. TO3 group exhibited significant decreases in the gingival tissue levels of PGE2, PGF2alpha, LTB4, and PAF compared to the LPS group (P<0.05). PGE2 and PGF2alpha levels in TO3 group were similar to those of the saline group (P>0.05), while LTB4 and PAF levels were statistically higher than the saline group (P<0.05). Prophylactic plus therapeutic usage of omega-3 fatty acid provided similar levels of all these mediators to those of the saline controls (P>0.05).. Therapeutic omega-3 fatty acid significantly reduced the gingival tissue levels of PGE2, PGF2alpha, LTB4, and PAF in experimental periodontitis. Furthermore, prophylactic usage of omega-3 fatty acid provided additional beneficial effects to the therapeutic administration by decreasing the gingival tissue levels of these mediators to levels of healthy tissue. These findings should be verified by longitudinal clinical trials investigating clinical and biochemical periodontal parameters to better define the possible role of omega-3 fatty acids in periodontal treatment.

Topics: Alveolar Bone Loss; Analysis of Variance; Animals; Dinoprost; Dinoprostone; Endotoxins; Fatty Acids, Omega-3; Gingiva; Immunoenzyme Techniques; Inflammation Mediators; Leukotriene B4; Male; Periodontitis; Platelet Activating Factor; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Statistics, Nonparametric

Topics: 6-Ketoprostaglandin F1 alpha; Arachidonic Acid; Arachidonic Acids; Chromatography, Gel; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Dinoprost; Dinoprostone; Epoprostenol; Humans; Periodontal Pocket; Periodontitis; Prostaglandins; Prostaglandins E; Prostaglandins F; Thromboxane A2

This study was undertaken to determine the ability of inflamed and normal gingival tissues to synthesize prostaglandins (PGs) from the precursor arachidonic acid. Thirteen samples of inflamed human gingival tissue and six samples of normal human gingival tissue were studied. The inflammation was characterized histologically. After incubation of the tissue with [14C]arachidonate, PG metabolites were separated by thin-layer chromatography and identified by comparison with co-chromatographed standards. Inflamed gingival tissue synthesized significantly larger amounts, compared to normal tissue, of 6-keto-PGF1 alpha (P less than 0.05), thromboxane B2 (P less than 0.01), PGD2 (P less than 0.05), and PGA2 (P less than 0.001). Some unidentified metabolites, possibly lipoxygenase products were detected in significantly (P less than 0.001) larger amounts in inflamed than in normal tissue.

Topics: 6-Ketoprostaglandin F1 alpha; Arachidonic Acid; Arachidonic Acids; Carbon Radioisotopes; Dinoprost; Dinoprostone; Gingiva; Gingivitis; Humans; Periodontitis; Prostaglandin D2; Prostaglandins; Prostaglandins A; Prostaglandins D; Prostaglandins E; Prostaglandins F; Thromboxane B2

Topics: Alveolar Process; Animals; Dinoprost; Dogs; Gingivitis; Nucleotides, Cyclic; Periodontitis; Prostaglandins E; Prostaglandins F