leukotriene-b4 and Gingival-Hemorrhage

Inflammatory and anti-inflammatory mediators may play a significant role in patients with gingivitis. The purpose of this study was to assess the short-term effects of the systemic administration of two different concentrations of aspirin (81 and 325 mg/day, by mouth) on clinical periodontal parameters and gingival crevicular fluid (GCF) levels of 15-epi-lipoxin A4 (15-epi-LXA4), lipoxin A4, leukotriene B4 (LTB4), prostaglandin E2 (PGE2), and interleukin (IL)-6 and -1beta in a sample of naturally occurring gingivitis patients.. At day 0, after initial screening for entry, baseline periodontal parameters, including bleeding on probing (BOP), periodontal probing depths (PDs), and plaque index (PI) were measured, and GCF was sampled from 12 intrasulcular sites with filter paper strips for the measurement of six types of inflammatory and anti-inflammatory mediators using competitive enzyme immunoassay and enzyme-linked immunosorbent assay (prevalues). Forty-seven subjects were assigned randomly to one of three treatment groups: placebo (15 subjects); aspirin, 81 mg (16 subjects); and aspirin, 325 mg (16 subjects) once daily. On day 7, subjects were recalled for the measurement of periodontal parameters and collection of GCF samples for the measurement of six types of mediators (postvalues).. Changes in inflammatory and anti-inflammatory mediator levels were not statistically significant for any of the three treatment groups. However, when pre- and postvalues were compared in the subjects receiving aspirin, 325 mg, there was a negative trend in the relationship between 15-epi-LXA4 and PGE2, whereas the relationship between LTB4 and PGE2 was not as strong. This might indicate that the subjects responding to aspirin-mediated PGE2 suppression effects produced higher 15-epi-LXA4 in GCF than non-responders. No statistically significant differences in PD and PI between pre- and postvalues were found for any of the three treatment groups. However, the results demonstrated a significant increase in BOP when aspirin, 325 mg was compared to placebo (P <0.001) and aspirin, 81 mg (P = 0.001).. Aspirin can have an affect on BOP in naturally occurring gingivitis patients. Although most of the inflammatory mediators did not show significantly detectable changes after aspirin treatment for 7 days, the trend of aspirin-associated increases of 15-epi-LXA4 implied that this recently discovered aspirin-dependent eicosanoid may be associated with the increased incidence of BOP observed in the subjects who received aspirin therapy.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Dental Plaque Index; Dinoprostone; Female; Gingival Crevicular Fluid; Gingival Hemorrhage; Gingivitis; Humans; Inflammation Mediators; Interleukin-1beta; Interleukin-6; Leukotriene B4; Lipoxins; Male; Periodontal Pocket; Placebos

Polyunsaturated fatty acids have the potential to attenuate inflammation by the synthesis of mediators of the 15-lipoxygenase pathways, which show opposite effects to the pro-inflammatory arachidonic acid metabolites such as leukotriene B4 (LTB4).. The aim of this clinical study was to evaluate the effects of topical application of n-6 or n-6 polyunsaturated fatty acids in patients with experimental gingivitis.. In each subject, similar teeth served as experimental and control over a 21-day non-hygiene phase and a 9-day resolving phase. Efficacy assessment was based on the bleeding on probing frequency (BOP) and the gingivocrevicular fluid volume (GCF). GCF was determined by inserting a filter paper strip for 30 s and measurements were performed on a Periotron 8000. The LTB4 concentration was analyzed by reversed-phase high-pressure liquid chromatography.. After 21 days of plaque growth, the BOP, GCF and LTB4 levels were significantly increased in all groups, with no differences between the control and experimental side. Rinsing of an area with established gingivitis for a 9-day period significantly reduced the GCF in the n-6 group (71.9 (18.7) versus 47.4 (11.4) Periotron Units, median (inter quartile range)).. The topical application of n-6 or n-6 fatty acids failed to inhibit the development of experimental gingivitis. Rinsing with n-6 fatty acids could reduce the level of GCF in established experimental gingivitis.

Topics: Administration, Topical; Adult; Analysis of Variance; Case-Control Studies; Chromatography, High Pressure Liquid; Double-Blind Method; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Fatty Acids, Unsaturated; Female; Fish Oils; Gingival Crevicular Fluid; Gingival Hemorrhage; Gingivitis; Humans; Leukotriene B4; Male; Matched-Pair Analysis; Mouthwashes; Normal Distribution; Statistics, Nonparametric; Triglycerides

The anti-inflammatory effect of n-3 PUFA on the gingivae has already been demonstrated in animal models. The aim of this double-blind, randomized pilot study versus placebo is to evaluate this action in human experimentally-induced gingivitis. For 14 days (D0-D14), 37 healthy volunteers practised intensive oral hygiene, then abstained from brushing their teeth for 21 days (D14 to D35). On D28, the patients were randomized into 2 groups: 18 received the drug (fish oil: 30% n-3 PUFA) and 19 received the placebo (olive oil containing only 1% of n-3 PUFA) at a daily dosage of 6 g (i.e., 1.8 g of n-3 PUFA) 3x for 8 days (D28-D35). The plaque (PI), gingival (GI) and papillary bleeding (PBI) indices were measured on D14, D28 and D35. On D28 and D35, 10 volunteers underwent removal of an inter-dental vestibular papilla, between the 1st and the 2nd superior premolars, to measure out arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA). A gingival biopsy was also taken in another 11 patients, to assay prostaglandin E2 (PGE2) and leukotriene B4 (LTB4). The clinical results of the trial demonstrated, in particular, a significant reduction of GI in the treated group (p < 0.05, Student t-test), but no significant difference between the groups. The biochemical results showed that EPA, DHA and DPA were found in the cells sampled, at higher levels in the subjects taking the drug, with a significant difference for EPA between the 2 groups (p < 0.05, Student t-test). The levels of AA, PGE2 and LTB4 are reduced in the experimental group and increased in the control group, with no significant difference. The LTB4 levels decreased but this difference just failed to reach significance (p = 0.09. Student t-test). This human experimental gingivitis study demonstrated that n-3 PUFA induced a tendency towards reduced inflammation but it was not possible to conclude significant efficacy.

Topics: Adolescent; Adult; Anti-Inflammatory Agents; Arachidonic Acids; Dental Plaque Index; Dinoprostone; Disease Models, Animal; Docosahexaenoic Acids; Double-Blind Method; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Female; Fish Oils; Gingiva; Gingival Hemorrhage; Gingivitis; Humans; Leukotriene B4; Male; Olive Oil; Periodontal Index; Pilot Projects; Placebos; Plant Oils

The aim was to study the levels of prostaglandin E2 (PGE2), leukotriene B4 (LTB4), and matrix metalloproteinase-9 (MMP-9) in gingival crevicular fluid (GCF) from Down syndrome patients exhibiting gingival inflammation. The levels of PGE2, LTB4, and MMP-9 were determined in GCF from 18 Down syndrome patients and from 14 controls matched with respect to age and degree of gingival inflammation. Probing depth (PD) and gingival inflammation, assessed by bleeding on probing (BOP), were determined around all teeth. In each patient, GCF was collected from 6 sites (16m, 26m, 36m, 46m, 41m, 11d) using periopaper, and the volume was determined using Peritron 8000. The PGE2 and LTB4 levels were determined using RIA kits and MMP-9 level using ELISA kits. The degree of gingival inflammation, expressed as mean value of BOP (%) as well as the volume of GCF, was similar between Down syndrome patients and controls. The mean levels of PGE2, LTB4, and MMP-9 were significantly (P<0.05) higher in GCF from Down syndrome patients compared to controls. When comparing the two groups, the correlation coefficients for LTB4 to BOP and PD, respectively, as well as for MMP-9 to BOP significantly differed between Down syndrome and controls (P<0.05). The study supports the concept of an altered host response in periodontal tissue in Down syndrome subjects.

Topics: Adolescent; Adult; Analysis of Variance; Case-Control Studies; Child; Dinoprostone; Down Syndrome; Gingival Crevicular Fluid; Gingival Hemorrhage; Gingival Pocket; Gingivitis; Humans; Leukotriene B4; Linear Models; Matrix Metalloproteinase 9; Periodontal Index

Cyclosporine A (CsA) is a potent immunosuppressant effectively used to prevent organ transplant rejection and also to treat several systemic diseases. CsA-induced gingival overgrowth (CsA GO) is the most widely seen side effect of this drug; its pathogenesis is not completely understood. The aim of the present study was to identify the role of leukotriene B4 (LTB4) and platelet activating factor (PAF) in the pathogenesis of CsA GO.. LTB4 and PAF levels were detected in gingival crevicular fluid (GCF) samples from renal transplant patients receiving CsA therapy and exhibiting CsA GO, from patients with gingivitis and from periodontally healthy subjects. Plaque index, papilla bleeding index, and hyperplastic index were recorded at each study site. GCF samples and clinical data were obtained from: 2 sites exhibiting CsA GO (CsA GO+) and 2 sites not exhibiting CsA GO (CsA GO-) in each CsA-treated patient; 2 diseased sites in each patient with gingivitis; and 2 healthy sites in each subject with clinically healthy periodontium. LTB4 was extracted from the samples by solid-phase method using C18 cartridge and purified by high-performance liquid chromatographic (HPLC) method and analyzed by radioimmunoassay (RIA). PAF was extracted from GCF samples passing through amberlit resin columns, purified by HPLC, and analyzed by RIA.. Total amounts of LTB4 and PAF in GCF were higher in CsA GO+ sites compared to the healthy sites from healthy controls. However, the amount of LTB4 and PAF elevation in CsA GO+ sites was not significantly higher than those in diseased sites. Clinical degrees of gingival inflammation were also similar between CsA GO+ and diseased sites. LTB4 and PAF total amounts in GCF were higher in CsA GO+ sites compared to CsA GO- sites in the same subjects, but this difference just failed to reach significance. Similar findings were obtained with concentration data.. The results of this study indicate that CsA therapy does not have a significant effect on GCF LTB4 and PAF levels and that gingival inflammation seems to be the main reason for their elevation. In CsA-treated patients, alterations in LTB4 and PAF levels might play a role in CsA GO through some asyet unknown mechanism. To our knowledge, this is the first report describing the levels of lipid mediators in GCF of CsA-treated patients. We assume that further studies will contribute to the understanding of the pathogenesis of CsA-induced gingival overgrowth.

Topics: Adolescent; Adult; Chromatography, High Pressure Liquid; Cyclosporine; Dental Plaque Index; Female; Gingival Crevicular Fluid; Gingival Hemorrhage; Gingival Hyperplasia; Gingival Overgrowth; Gingivitis; Humans; Immunosuppressive Agents; Kidney Transplantation; Leukotriene B4; Male; Periodontium; Platelet Activating Factor; Radioimmunoassay

Ketoprofen creams were evaluated for the treatment of periodontal disease in a placebo-controlled, double-blind study in the rhesus monkeys, Macaca mulatta. Two formulations containing ketoprofen (1%), with or without vitamin E, were evaluated against appropriate controls (8 monkeys per group). Two weeks prior to treatment, the animals received prophylaxis on only the left side of the mouth (spontaneous model). Selected teeth on the right side of the mouth were ligated (ligature model). The creams were administered to the gingiva once daily at a standard dose of 1.8 ml per monkey for 6 months. Clinical assessments were made 2 wk before initiation, at baseline and 1, 2, 3 and 6 months post-treatment. The clinical parameters included plaque formation, gingival redness, edema, bleeding on probing and Ramfjord Attachment Level measurements (RAL). Radiographs were taken at 2 wk before initiation, baseline and at 3 and 6 months post-treatment. Digital, subtraction radiography was used to measure vertical linear bone loss along the interproximal root surfaces of the left and right mandibular first molars. Gingival crevicular fluid (GCF) was collected for biochemical assays on PGE2, TxB2, LTB4, IL-1 beta and TNF alpha. There were no significant differences among groups with respect to gingival indices. Radiographic data demonstrated significant positive effects on bone activity in both groups treated with ketoprofen formulations with improvement over time in the ligature model (0.01 < or = p < or = 0.04). The placebo group exhibited bone loss of 1.96 +/- 0.48 and 1.40 +/- 0.56 mm per site at 3 and 6 months, respectively. The group treated with ketoprofen cream showed an apparent bone gain of 0.28 +/- 0.41 and 0.78 +/- 0.47 mm per site at 3 and 6 months, respectively. The group treated with ketoprofen cream containing vitamin E showed a mean bone loss of 0.41-0.48 mm per site at 3 months with improvement to an apparent bone gain of 0.31 +/- 0.44 mm per site at 6 months. The biochemical data demonstrated early and significant suppression of GCF-LTB4 by both ketoprofen formulations at 1 month, which preceded the significant suppression of GCF-PGE2 at 2 and 3 months in the ligature model (p < 0.003) and at 2 to 6 months in the spontaneous model (p < 0.02). We conclude that ketoprofen at 1% level in suitable topical vehicles can effectively inhibit GCF-LTB4 and GCF-PGE2 and positively alter alveolar bone activity in the ligature-induced model of periodontitis in the m

Topics: Administration, Topical; Alveolar Bone Loss; Animals; Anti-Inflammatory Agents, Non-Steroidal; Dental Plaque; Dinoprostone; Double-Blind Method; Edema; Emollients; Female; Follow-Up Studies; Gingival Crevicular Fluid; Gingival Hemorrhage; Gingivitis; Interleukin-1; Ketoprofen; Leukotriene B4; Macaca mulatta; Male; Molar; Periodontal Attachment Loss; Periodontitis; Placebos; Radiographic Image Enhancement; Random Allocation; Subtraction Technique; Thromboxane B2; Tumor Necrosis Factor-alpha; Vitamin E