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Notes: The effect of two non-steroidal anti-inflammatory drugs, indomethacin and flurbiprofen, on the progression of periodontal disease was studied in 16 beagle dogs over a 12-month period. Standardized radiographs were used to measure the rate of bone loss. Following a 6-month pretreatment baseline period, 5 dogs were dosed daily with 1.0 mg/kg indomethacin, 5 dogs were dosed daily with 0.02 mg/kg flurbiprofen, and 6 dogs were dosed with empty gelatin capsules for a 6-month period. In the untreated control dogs, the rate of bone loss in the treatment period significantly increased from baseline. In contrast, the rate of bone loss significantly decreased from baseline in the flurbiprofen-treated dogs. In the indomethacin-treated dogs, rate of bone loss in the treatment period was not significantly different from baseline. The data indicate that both flurbiprofen and indomethacin inhibit alveolar bone loss in beagles compared to untreated controls. The data also indicate that with the dosages employed flurbiprofen is overall more effective.

Notes: The non-steroidal anti-inflammatory drug(NSAID) naproxen was studied in 11 beagle dogs over a 13-month period to determine its effect on the progression of periodontitis. Following a 6-month pretreatment period, 5 dogs received naproxen daily at a dosage of 2.0 mg/kg for 1 month, then 0.2 mg/kg for 6 months. Six control dogs received a gelatin capsule daily as placebo. Standardized radiographs were used to measure the rate of bone loss during the pretreatment and treatment periods. In the control dogs, the rate of bone loss was seen to increase during the treatment period although the increase was not statistically significant. In dogs treated daily with naproxen, the rate of bone loss in the treatment period was significantly less at 4 months of treatment; however, at 7 months the difference, though lower than pretreatment rate, was not significant. When the percent change in rate of bone loss during the overall 7-month treatment period was compared with pretreatment rate, the control dogs demonstrated a 38% increase in rate of bone loss during the treatment period contrasting with a 61% decrease in bone loss rate in naproxen-treated dogs. The data indicate that the non-steroidal anti-inflammatory drug naproxen can significantly inhibit alveolar bone loss in beagles. At 4 months of treatment the rate of bone loss in the naproxen-treated dogs was significantly less than pretreatment, but at 7 months of treatment the rate was no longer statistically significantly less than baseline. This probably reflects a dose response to naproxen treatment for, after 30 days of the treatment period, the naproxen dosage was reduced 10-fold due to tolerance by the beagle.

Notes: A single-blind investigation was designed to study the effects of piroxicam in preventing gingival inflammation and plaque formation in beagle dogs. Twelve 1-year-old beagles were brought to optimum oral hygiene and gingival health. Thereafter, they were fed a moist plaque-promoting diet and were divided into three groups. The first group received daily administration of 1.0 ml placebo gel (methylcellulose) painted on the teeth. The second group received 1.0 ml of gel containing 2 mg/ml piroxicam and the third group received 1.0 ml liquid containing 2 mg/ml of piroxicam. Placebo and test solutions were applied daily, and dogs were examined biweekly for evaluation of plaque accumulation, gingival inflammation, bleeding upon gentle probing and tooth staining. Data were analyzed using the Krushkal-Wallis test. Over the treatment period, plaque accumulation was substantial in all three groups and was not significantly different between the three groups. By week 2, the gingival index in the piroxicam-treated dogs was significantly lower than that of the placebo-treated group and remained so throughout the study, with the exception of wk 6 and 12 in the topical gel-treated group. Mean percent bleeding sites were also significantly less in the piroxicam-treated groups than in the control dogs. Staining of the teeth increased for all groups over the 16-wk treatment period. These data indicate that piroxicam can significantly inhibit the development of gingival inflammation in beagle dogs.

Notes: The effect of the non-steroidal anti-inflammatory drug, ibuprofen, on the progression of periodontal disease was studied in 22 beagle dogs over a 13-month period. Standardized radiographs were used to measure the rate of bone loss. Following a 6-month pretreatment baseline period. 6 dogs were treated daily with 4 mg/kg ibuprofen, 5 dogs were treated with 4 mg/kg ibuprofen in a sustained release preparation, 5 dogs were treated with 0.4 mg/kg ibuprofen and 6 untreated dogs served as controls. In the untreated control dogs the rate of bone loss in the treatment period did not change significantly from baseline, although the rate was increased. In both the 4.0 mg/kg and sustained release 4.0 mg/kg ibuprofen-treated dogs the rate of bone loss in the treatment period was significantly less than the pretreatment period rate. In the 0.4 mg/kg ibuprofen-treated dogs the rate of bone loss, although reduced, was not significantly less than the pretreatment rate. When the rate of bone loss in the control dogs was compared with the rate of bone loss in the ibuprofen-treated dogs, all three ibuprofen-treated groups of dogs had significantly less bone loss than the control dogs. The untreated control dogs lost 10 teeth during the treatment period, whereas the 4.0 mg/kg and 0.4 mg/kg ibuprofen-treated dogs lost 6 teeth and the sustained release 4.0 mg/kg ibuprofen-treated dogs lost 2 teeth during the treatment period. The data indicate that a propionic acid derivative, the non-steroidal anti-inflammatory drug, ibuprofen, can significantly inhibit alveolar bone loss in beagles. Sustained release ibuprofen. which gave consistently greater blood levels over 24 h, was overall more effective.

Notes: The effect of the non-steroidal anti-inflammatory drug flurbiprofen, topically applied, on the progression of periodontal disease was studied in 12 beagle dogs over a 13-month period. Standardized radiographs were used to measure the rate of bone loss. Following a 6-month pretreatment baseline period, 6 dogs were treated daily with 0.3 mg flurbiprofen gently applied to the gingival margin in 1 ml of gel vehicle. Six untreated dogs served as controls. In the untreated control dogs the rate of bone loss in the treatment period did not change significantly from baseline, although the rate was elevated by 38%. In contrast, the rate of bone loss significantly decreased by 71% from baseline in the flurbiprofen-treated dogs. The untreated control dogs lost 10 teeth during the treatment period whereas the topical flurbiprofen-treated dogs lost only 1 tooth. The data indicate that topical application of flurbiprofen in a gel vehicle significantly inhibits alveolar bone loss in beagles over a 7-month treatment period. The data also indicate that topical flurbiprofen is associated with the loss of considerably less teeth than in untreated control dogs over the 7-month treatment period.

Notes: This investigation focuses on the changes in the concentrations of cyclooxygenase (CO) products present within the crevicular fluid in naturally-progressing periodontitis in the beagle and the effects of various non-steroidal anti-inflammatory drugs (NSAIDs) on these metabolite levels and disease progression. Six groups of 5–6 beagles with periodontitis were followed for 6 months to determine the pretreatment rate of radiographic bone loss. At baseline, groups of animals were placed on soft chow to promote disease progression. Groups were treated with either placebo, three different formulations of systemic ibuprofen, systemic naproxen or topical flurbiprofen. During the 6-month treatment phase, crevicular fluid (CF) samples and radiographs were taken at regular intervals. Radioimmunoassay of CF samples from untreated animals demonstrated a steady increase in prostaglandin E2 (PGE 2) over baseline values. At 1 month, CF-PGE2 levels increased 2-fold over baseline and, by 6 months, had reached a 5- to 6-fold elevation. Crevicular fluid thromboxane B2 (CF-TxB2) levels rapidly reached a 4- to 5-fold peak over baseline at 1 month and subsequently dropped to a 2-fold elevation for the remainder of the study. The rate of bone loss (BLOSS) in untreated animals increased 38% during the 6-month period, as compared to baseline pretreatment BLOSS rates. Overall, there was a significant depression in the CF levels of both PGE2 and TxB2 in all NSAID-treated groups. All NSAID treatments significantly retarded BLOSS, ranging from 21.0–36.9% of the control BLOSS rate. The topical application of flurbiprofen was as effective in depressing CF levels of PGE2 and TxB2 as systemic or sustained release formulations of other NSAIDs. The data further substantiate the concept that much of the BLOSS that occurs in periodontal disease is mediated by products of the cyclooxygenase pathway. Furthermore, CO activation represents a major regulatory step in bone destruction and may thereby serve as an important site for pharmacological modulation.

Notes: The effect of zinc sulfadiazine (ZnSD) and silver sulfadiazine (AgSD) on developing plaque formation and gingivitis was studied in 12 beagle dogs over a 14-week period. Plaque and gingival indices were used to measure plaque formation and gingivitis. During a 2-wk baseline period each dog was brought to optimal gingival health with prophylaxis and tooth brushing. Thereafter, 4 dogs were treated twice daily with topical application of 3.0% zinc sulfadiazine; 4 dogs were treated with 2.0% silver sulfadiazine while 4 dogs treated with placebo gel served as controls over a 12-wk treatment period. At wk 2 of treatment, all three groups of dogs showed an increase in plaque build-up on their teeth from baseline. By wk 6, plaque accumulation on the teeth was significantly less in dogs treated with either ZnSD or AgSD compared to control dogs. At wk 2 of treatment, gingival inflammation was increased from baseline in all three groups. Thereafter, over the course of the 12-wk treatment period, gingival inflammation in the ZnSD and the AgSD treated dogs was significantly less than the placebo treated dogs. The data indicate that both ZnSD and AgSD inhibit developing plaque formation in beagles. This significant inhibition of plaque formation was accompanied by a significant reduction in gingival inflammation.

Notes: The effect of two non-steroidal anti-inflammatory drugs, indomethacin and flurbiprofen, on the progression of alveolar bone loss and on the crevicular fluid (CF) levels of four arachidonic acid metabolites was compared in 16 beagle dogs over a 12-month period. Standardized radiographs were used to measure the rate of bone loss. Radioimmunoassay was used to measure CF levels of PGE2, PGF2α, TxB2 and 6K-PGF1α. Following a 6-month pretreatment baseline period, 5 dogs were dosed daily with 1.0 mg/kg indomethacin, 5 dogs were dosed daily with 0.02 mg/kg flurbiprofen, and 6 dogs were dosed with empty gelatin capsules for a 6-month period. With the administration of either indomethacin or flurbiprofen. the CF levels of PGE2, PGF2α, and TxB2 were similarly significantly decreased; 6K-PGF1α levels were not altered. Indomethacin and flurbiprofen did not have a similar effect on reducing the rate of alveolar bone loss. Flurbiprofen significantly decreased rate of bone loss from baseline whereas indomethacin did not. The data indicate that indomethacin and flurbiprofen inhibit CF arachidonic acid metabolite levels in a similar manner, but not rate of bone loss. The data suggest that flurbiprofen's striking effect on inhibiting rate of bone loss cannot be solely attributed to simple cyclooxygenase inhibition with a reduction in CF prostaglandin levels.

Notes: There is increasing interest in how pathways of tissue destruction around dental implants are similar as for teeth and how these pathways can be modulated to slow loss of supporting bone. The purposes of this study were to develop a short-term animal model to study the effect of the nonsteroidal anti-inflammatory drug flurbiprofen, on slowing the rate of induced peri-implant bone resorption. A total of 20 cylindrical titanium implants were placed in 2 beagle dogs using a low-trauma surgical technique. During the 3-month healing period without functional loading of the implants, daily oral hygiene was performed to maintain a Gingival Index of 0 to 0.5. At completion of the healing period, a baseline evaluation was performed which included the uptake of the bone-seeking radiopharmaceutical (BSRU)99mtechnetium-tin-diphosphonate (99mTc-Sn-MDP) in peri-implant bone and standardized radiographs. Peri-implantitis was induced with 4-O silk ligatures, cessation of oral hygiene and soft diet. One beagle was given 0.02 mgikg of flurbiprofen by mouth; the other received a placebo. BSRU and radiographic height of bone were remeasured to calculate the rate of bone loss during the 60-day treatment period. The percent rate of bone loss during the study period was calculated from the radiographs using a computer-assisted method. The radiopharmaceutical uptake for the flurbiprofen-treated implants remained unchanged. However, BSRU for placebo-treated implants was significantly increased from baseline. Radiographic measurements of bone height revealed that the mean rate of bone loss around implants in the flurbiprofen-treated dog (0.066±0.351%/month) was significantly lower than the rate around implants in the placebo-treated dogs (5.729±0.384%/month) over the 60-day treatment period. These data indicate that peri-implant bone loss can be rapidly induced and measured in the beagle and that flurbiprofen. administered orally, can significantly decrease the rate of induced peri-implant bone loss.

Notes: Abstract The aim of this study was to evaluate the effect of nisin, an antimicrobial peptide, on the development of plaque and gingivitis in beagle dogs when compared with 0.12% chlorhexidine and a placebo. 16 female beagle dogs 1 year of age were brought to optimum gingival health by scaling, root planing and polishing. At the conclusion of the pretreatment phase, the dogs were divided into 4 groups for the application of the test agents and were placed on a plaque promoting diet of Purina Dog Chow softened with water. Test agents included 100 μg/ml nisin and 300 μg/ml nisin formulated in a vehicle containing 1 mM NaEDTA; negative control comprised of exactly the same formulation but omitting nisin; and 0.12% chlorhexidine as Peridex®. Throughout the treatment period, formulations were applied 2 × daily to premolar teeth in each quadrant for 1 min using a Monojet syringe. The development of plaque and gingivitis was monitored at 15, 27, 39, 53, 74 and 88 days during the treatment phase using standard measurements of gingival index, plaque index, stain index and bleeding to probing. Throughout the treatment phase, plaque accumulation increased in all groups, but the rate of plaque build-up was less in groups treated with either nisin or chlorhexidine formulations compared with the placebo treated group. The gingival index of dogs in all groups increased throughout the study period. However, from day 27 onward, the groups receiving nisin had lower gingival index scores than did the placebo group. At day 39 and onward, the chlorhexidine group had significantly lower gingival index scores than the placebo group. All groups demonstrated an increased in % Weeding sites. However, from day 27 onward, the 300, μg/ml nisin group and from day 39 the 100 μg/ml group, had significantly fewer % bleeding sites than the placebo group. An evaluation of the staining intensity index revealed that staining for the chlorhexidine-treated group was significantly greater than that of placebo and nisin at days 27, 74 and 88. In conclusion, nisin is an antimicrobial agent and is effective in the reduction of plaque build-up and gingivitis in the beagle dogs.