Effects of a cyclic NSAID regimen on levels of gingival crevicular fluid prostaglandin E2and Interleukin-1ß: A 6-month randomized controlled clinical trial.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used for inflammation control and pain relief. However, while the adjunct use of NSAIDs is avoided for periodontal therapy because of related side effects, cyclic administration of NSAIDs may reduce or eliminate these effects. We evaluated the effect of a cyclic diclofenac potassium (DP) regimen on clinical parameters and levels of prostaglandin E2 (PGE2) and interleukin-1ß (IL-1ß) in the gingival crevicular fluid (GCF) of individuals with periodontitis. MATERIALS AND METHODS: The study protocol was approved by the Ethics Committee (2000/071). Forty-one individuals with chronic periodontitis (33 men, 8 women) were divided into two groups (test and control) after initial periodontal therapy. During this 6-month, randomized, double-blind, placebo-controlled study, test (n = 28) and control (n = 13) groups were administered a cyclic regimen of DP (50 mg, twice daily) or placebo. Clinical measurements and GCF sample collections were made at baseline, 2, 4, and 6 months. GCF levels of PGE2and IL-1ß were determined using enzyme immunoassay and enzyme-linked immunoassay kits, respectively. RESULTS: At baseline, no significant differences existed between groups for plaque indices, gingival indices, bleeding on probing, probing depth (PD), or attachment levels (P > 0.05). Compared with the control group, cyclic regimen in the test group suppressed increased levels of PGE2found in GCF at the end of the study (P < 0.05). Significant differences for PD and relative attachment gain were also noted in favor of the test group (P < 0.05). CONCLUSIONS: These results suggest that a cyclic regimen of DP may be efficacious in the management of chronic periodontitis in adults.

Gingival crevicular fluid levels of monocyte chemoattractant protein-1 in patients with aggressive periodontitis.

OBJECTIVES: The purpose of this study was to investigate the gingival crevicular fluid (GCF) levels of monocyte chemoattractant protein (MCP)-1 in aggressive periodontitis (AgP) and whether GCF MCP-1 levels differ among localized (L) AgP and generalized (G) AgP. MATERIAL AND METHODS: A total of 160 subjects including 80 AgP and 80 age- and gender-matched periodontally healthy (H) controls were recruited in this cross-sectional study (NCT02927704). GCF samples were collected from 160 patients including 50 LAgP, 30 GAgP, and 80 H. Volume of GCF was measured by Periotron 8000® , and enzyme-linked immunosorbent assay was used to assess MCP-1 levels. RESULTS: Compared to H controls, all clinical parameters and total amounts (pg 30 s-1 ) of MCP-1 were significantly higher in subjects with LAgP and GAgP (P < 0.05). Although concentrations of GCF MCP-1 did not differ between LAgP and GAgP (P > 0.05), total amounts of MCP-1 were higher in GAgP than LAgP (P < 0.05). CONCLUSION: It can be concluded that the total amount of MCP-1 level in GCF may be a potential determinant in AgP subjects. Increased MCP-1 levels in line with the degree of periodontal destruction in GAgP patients reveal that MCP-1 can be used to understand the disease pathogenesis of LAgP and GAgP.

Effects of alpha-tocopherol on gingival expression of inducible nitric oxide synthase in the rats with experimental periodontitis and diabetes.

BACKGROUND: The aim of this study was to investigate effects of α-tocopherol and/or insulin on the number of gingival inducible nitric oxide synthase (iNOS) positive cells in rats with experimental periodontitis with or without streptozotocin (STZ)-induced diabetes. MATERIALS AND METHODS: A total of 60 Sprague-Dawley rats were divided into three groups: Group I: The group without diabetes; Group II: The group with STZ-induced diabetes; Group III: The group with STZ-induced diabetes receiving insulin therapy. All animals received anesthesia, and 3/0 silk suture was inserted around the mandibular molar teeth. All groups were divided into subgroups receiving saline (Groups IA, IIA, IIIA) and α-tocopherol injection (Groups IB, IIB, IIIB). After a period of 3 weeks, all rats were sacrificed, and the number of gingival iNOS positive cells was analyzed using image analysis software. RESULTS: Applying α-tocopherol suppressed the number of gingival iNOS positive cells in Groups IB, IIB, and IIIB compared to application of saline (Groups IA, IIA, and IIIA) (P < 0.05). Numbers of gingival iNOS positive cells were found to be similar in the Groups I and III (P > 0.05). CONCLUSIONS: Within limitations of the current study, this is the first study one may suggest that α-tocopherol may reduce oxidative damage in the gingiva of the rats with periodontitis with or without STZ-induced diabetes and increase effects of insulin.

Efficacy of treatment with a kinaesthetic ability training device on balance and mobility after stroke: a randomized controlled study.

OBJECTIVE: To investigate whether the addition of a kinaesthetic ability training device could enhance the effect of a conventional rehabilitation programme on balance and mobility in hemiparetic patients late after stroke. DESIGN: Randomized, controlled, assessor-blinded trial. SETTING: The rehabilitation ward of a university hospital. Thirty hemiparetic patients (mean age (SD) of 57.4 (8.1) years) late after stroke (mean time since stroke (SD) 545.2 (99.9) days) were assigned randomly to an experimental or a control group. INTERVENTIONS: The control group (n = 15) participated in a conventional rehabilitation programme. The experimental group (n = 15) participated in balance training with a kinaesthetic ability training device in addition to a conventional rehabilitation programme for four weeks, five days a week. OUTCOME MEASURES: Kinaesthetic ability training static and dynamic balance indices, balance and lower extremity subscores of the Fugl-Meyer Stroke Assessment Instrument (FMA), total motor and locomotor subitem scores of the Functional Independence Measure (FIM) were evaluated at baseline and after treatment. RESULTS: The experimental group had greater improvement in measures of balance including static (P = 0.045) and dynamic balance index (P = 0.001) and FMA balance score (P = 0.001) than the control group. No between-group differences were detected in subscore of FMA, total motor and locomotor subscores of FIM. There were significant improvements in balance subscores of FMA, static and dynamic balance indexes in the experimental group and in sub-item scores of FIM and lower extremity scores of FMA in both groups. CONCLUSION: Kinaesthetic ability training in addition to a conventional rehabilitation programme is effective in improving balance late after stroke. However, this improvement is not reflected in individual functional status.

Effects on the clinical indices and gingival crevicular fluid enzyme activities of the cyclical regimen of low-dose doxycycline therapy for adult periodontitis.

The purpose of this study was to determine the effect of cyclic regimen of low dose doxycycline (20 mg) or placebo therapy following scaling and root planing on clinical parameters and crevicular fluid alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase and elastase activities. Fifteen adults (13 males, 2 females) with moderate to advanced adult periodontitis were recruited for the study. The LDD-treated group (n = 8 subjects) self administered low dose doxycycline b.i.d. (20 mg, p.o.) from time (treatment) to 2 months and then no drug from 2 to 4 months and finally low-dose doxycycline b.i.d. from 4 to 6 months (i.e. "cyclical" regimen). The placebo-treated group (n = 7 subjects) was asked to take placebo capsules (containing inactive filler; i.e. starchflour) b.i.d. according to the same "cyclical" regimen. No differences were found between LDD- and placebo-treated groups regarding any of the clinical parameters and gingival crevicular fluid enzyme activities. The relative attachment gain was significantly improved in both groups. The "cyclical" regimen of low-dose doxycycline was not found to reduce alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase and elastase activities in gingival crevicular fluid of the adult periodontitis patients over a 6-month time period.

Implant-supported overdenture therapy: a 3- to 8-year prospective study.

Inflammatory changes in periimplant soft tissues and loss of alveolar bone can develop as in periodontal diseases. This clinical phenomena has been described as periimplantitis. Microorganisms such as Gram-negative anaerobic rods, spirochetes, and bacteroides that are seen in subgingival flora in periodontitis have also been found in sulcular microflora in periimplantitis. The purpose of this study was to evaluate periimplant tissue changes in totally edentulous patients who had implant-supported overdentures for 3 to 8 years (5-5.5 years) clinically from both a subjective and an objective point of view. The clinical parameters used in this study can be helpful in the evaluation of periimplant tissue health.

The effect of chronic stress on hepatic and gastric lipid peroxidation in long-term depletion of glutathione in rats.

The effect of chronic stress (immobilization and cold) on hepatic and gastric thiobarbituric acid reactive substances (TBARS) and vitamin C levels were investigated in rats having long-term depletion of glutathione (GSH) by applying buthionine sulfoximine (BSO). GSH and vitamin C levels decreased and TBARS levels increased in the liver and stomach of rats subjected to stress. Long-term BSO administration along with stress caused no additional changes in these parameters. These results may indicate that long-term glutathione depletion did not potentiate stress-induced hepatic and gastric lipid peroxidation.

Mitochondrial lipid peroxides and antioxidant enzymes in the liver following phorone-induced glutathione depletion.

The levels of lipid peroxidation product (malondialdehyde = MDA) and vitamin C and the activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were determined in the liver and its mitochondrial fraction, in the rats 2 and 18 hr after the injection of phorone, a glutathione (GSH) depleting agent. GSH levels decreased in liver homogenate and its mitochondrial fraction after 2 hr of phorone treatment, but these values returned to normal levels at 18 hr. In GSH depleted conditions, hepatic vitamin C levels increased, GSH-Px and SOD activities remained unchanged in mitochondrial and post-mitochondrial fractions. These results indicate that GSH depletion per se does not influence lipid peroxidation and GSH-Px and SOD activities in the liver and the mitochondrial fraction.

Evidence for oxidative stress in the hepatic mitochondria of bile duct ligated rats.

Lipid peroxidation increased both in the liver homogenates and in the hepatic mitochondrial fraction of bile duct ligated (BDL)-rats. Although mitochondrial superoxide dismutase (SOD) activity did not change in the liver, glutathione (GSH) levels and glutathione peroxidase (GSH-Px) activity decreased in hepatic mitochondrial fraction of BDL-rats as compared to sham-operated rats. In addition, GSH-Px and glutathione transferase (GST) activities decreased but SOD activity remained unchanged in the post-mitochondrial fraction of the liver from BDL-rats. However, erythrocyte lipid peroxide and GSH levels did not change in BDL-rats. In conclusion, our results show that the disturbance of oxidant-antioxidant balance especially in mitochondria may be responsible for cholestatic liver injury in BDL-rats.

Lipid peroxides, glutathione, gamma-glutamylcysteine synthetase and gamma-glutamyltranspeptidase activities in several tissues of rats following water-immersion stress.

The effects of water-immersion restraint (WIR) stress on lipid peroxide, glutathione (GSH), glutathione peroxidase (GSH-Px), gamma-glutamylcysteine synthetase (gamma-GCS) and gamma-glutamyltranspeptidase (gamma-GT) activities in several tissues of rats were investigated. Hepatic and intestinal lipid peroxide levels were increased significantly in the WIR stress group. In both tissues, GSH levels were significantly decreased and gamma-GCS activity was significantly increased. In addition, gamma-GT activities remained unchanged in both tissues following WIR stress. However, lipid peroxide and GSH levels did not change in the stomach and brain in the WIR stress group compared to the control group. These results suggest that lipid peroxidation, but not the depression of GSH synthesis and/or the increase of GSH breakdown may be a factor in hepatic and intestinal GSH reduction following WIR stress.

Hepatic gamma-glutamyl cysteine synthetase and gamma-glutamyl transpeptidase activities in galactosamine-treated rats.

Liver homogenate glutathione (GSH) content, lipid peroxide levels and the activities of GSH metabolizing enzymes were studied in rats after 24 hours of galactosamine (GalN) treatment. Lipid peroxide levels increased whereas hepatic GSH content was decreased significantly. On the other hand, hepatic gamma-glutamyl cysteine synthetase activity was unaffected by GalN administration but gamma-glutamyl transpeptidase activity increased.

Effect of depletion of glutathione by buthionine sulfoximine on lipid peroxidation in rats acutely treated with ethanol.

1. The effect of depletion of glutathione (GSH) by DL-buthionine-S,R-sulfoximine (BSO) on lipid peroxidation in rats acutely treated with ethanol was investigated. 2. BSO pretreatment has not been found to potentiate an increase in liver, brain and erythrocyte lipid peroxide levels.

Comparison of prolonged in vivo inhibitory activity of several potent bombesin (BN) antagonists on BN-stimulated amylase secretion in the rat.

New BN analogues designed to be competitive receptor antagonists at the BN/gastrin releasing peptide receptor(s) can exhibit diverse properties ranging from full antagonist, partial agonist or weak agonist activity, depending on the assay system and animal species employed. Here we evaluate the following 3 antagonists which have the most potent receptor affinities in several in vitro assay systems and are representative of 3 main classes of BN antagonists for their in vivo effects on pancreatic amylase secretion in the rat: [D-Cpa6,Phe14,psi 13-14]BN(6-14), [D-Phe6]BN(6-13) propylamide, and [D-Phe6]BN(6-13) methyl ester. After injection in the rat, the methyl ester was clearly the most potent antagonist and completely inhibited BN-stimulated amylase release at the 20 nmol/kg (IV bolus) for about 2 h. In contrast, the propylamide analogue at the 200 nmol/kg (IV bolus) dose produced incomplete inhibition of amylase release. Inhibition was transient and lasted for only about 1 h, possibly reflecting the significant agonist activity of this latter peptide in the rat pancreatic amylase secretion test in vitro. The psi-analogue, while being the longest acting analogue, was also incapable of lowering amylase to basal level at 50 times the BN dose, suggesting that it is a mixed agonist-antagonist in vivo as was also previously shown in vitro in the rat.

Galanin inhibits pancreatic amylase secretion in the pentobarbital-anesthetized rat.

The potent inhibitory effect of galanin on basal and pentagastrin-stimulated gastric acid secretion in vivo, and the presence of galanin-containing nerves in gastrointestinal tract and pancreas, suggested that this peptide may regulate the exocrine secretion of the GI system. Male rats were anesthetized with pentobarbital and the dose-dependent inhibitory effects of galanin on basal and stimulated pancreatic protein and amylase secretions were investigated in separate experiments. Galanin was administered intravenously in the following doses: 3, 6, 10, 15 and 20 micrograms/kg/h (0.93, 1.86, 3.1, 4.65 and 6.2 nmol/kg/h), and pancreatic secretions measured. The maximal effective dose of galanin (3.1 nmol/kg/h) on basal pancreatic secretions was found, and was used for evaluating the inhibitory effect of galanin on pancreatic protein and amylase secretions stimulated by bombesin, secretin and cholecystokinin. Galanin potently inhibited basal, bombesin-, secretin- and cholecystokinin-stimulated pancreatic protein and amylase secretion. Inhibitory effect of galanin was dose-dependent and biphasic.

Inhibitory effect of galanin on basal and pentagastrin-stimulated gastric acid secretion in rats.

The dose-dependent effects of galanin on basal and pentagastrin-stimulated gastric acid secretion in pentobarbital-anesthetized rats were examined. Intravenous infusion of galanin at doses of 0.31, 0.62, 1.25, 1.87, 3.11, and 6.22 nmol/kg-1/h-1 into pentagastrin-stimulated rats produced a diminution in gastric acid secretion which was maximal (54.7%) at the level of the 1.87 nmol/kg-1/h-1 dose. Furthermore, the effect was biphasic, since both lower and higher doses of peptide were less effective. At the optimum concentration of 1.87 nmol/kg-1/h-1 galanin also inhibited basal gastric acid secretion. We conclude that endogenous galanin might be involved in the physiologic regulation of gastric acid secretion.

The hepatic lipid peroxidation, copper and fibrosis in cholestatic rats.

Hepatic lipid peroxidation was shown to be stimulated in the livers of cholestatic rats with increased hydroxyproline levels. In another group, cholestatic rats were fed with a copper-supplemented diet to increase hepatic copper levels. Although liver copper concentrations increased about 16-fold in copper supplemented cholestatic rats compared to normally fed cholestatic rats, no change was observed either in hepatic lipid peroxidation or in hydroxyproline levels.