Biomedical subjects

T H Howell

Publications and source records attributed to T H Howell.

At least 19 recordsLinked to original sources

PubMed1992

Effects of NSAIDs on beagle crevicular cyclooxygenase metabolites and periodontal bone loss.

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 (PGE2) 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. Furthermore, CO activation represents a major regulatory step in bone destruction and may thereby serve as an important site for pharmacological modulation.

Administration, Oral↗

PubMed1991

Effect of the NSAID piroxicam, topically administered, on the development of gingivitis in beagle dogs.

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.

Administration, Topical↗

PubMed1991

Inhibition of alveolar bone loss in beagles with the NSAID naproxen.

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.

Alveolar Bone Loss↗

PubMed1991

The effects of short-term application of a combination of platelet-derived and insulin-like growth factors on periodontal wound healing.

Polypeptide growth factors are a class of potent natural biologic mediators which regulate many of the activities of wound healing including cell proliferation, migration, and metabolism. Platelet-derived growth factor (PDGF) and insulin-like growth factor-I (IGF-I) have been shown to regulate DNA and protein synthesis in bone cells in vitro and to interact synergistically to enhance soft tissue wound healing in vivo. We have hypothesized that the combination of PDGF and IGF-I may, therefore, enhance regeneration of both the soft and hard tissue components of the periodontium. To test this hypothesis we performed conventional periodontal surgery on all 4 quadrants of the mouth of 13 beagle dogs with naturally occurring periodontal disease. Following flap reflection, degranulation, and root planing, all premolar teeth in 2 quadrants of each dog received a combination of 3 micrograms of recombinant PDGF-B and IGF-I in a methylcellulose gel, while the premolar teeth in the contralateral quadrants received the gel alone. Teeth in 4 additional animals also received 125I-PDGF or 125I-IGF-I in the treated sites. The clearance rate of the 125I-labeled protein, changes in local bone metabolism, and amount of new bone and cementum with inserting collagen fibers were measured. The clearance studies revealed that the half-life of the factors at the site of application was 3.0 hours for IGF-I and to 4.2 hours for PDGF-B. Greater than 96% of the radio-labeled proteins was cleared by 96 hours and no radioactivity was detected 2 weeks after application. There was a significant (P less than 0.01) 2-fold increase in uptake of the bone-seeking radiopharmaceutical Technetium 99-MDP at 2 and 4 weeks in growth factor treated sites compared to controls, indicating that there was increased metabolic activity within the bone at these sites. Computer-aided histologic analyses of biopsies obtained at 2 and 5 weeks post-operatively revealed a significant (P less than 0.01), 5 to 10 fold increase in new bone and cementum in PDGF-B/IGF-I treated sites at both time points compared to controls receiving the placebo gel. The height and total area of new bone continued to increase from 2 to 5 weeks. The new bone underwent a normal maturation process as judged by histologic appearance. A physiologic periodontal ligament space was also formed between the new bone and new cementum. There was no increase in ankylosis in the treated sites.(ABSTRACT TRUNCATED AT 400 WORDS)

Alveolar Bone Loss↗

PubMed1991

Chemotherapeutic agents as adjuncts in the treatment of periodontal disease.

Periodontal disease is a broad term designating a number of infectious disease entities involving the supportive tooth structures. It has become clear that the various forms of periodontal disease are associated with specific groups of microorganisms. This evidence has led to treatment strategies that are primarily aimed at the suppression or elimination of specific periodontal pathogens. Until recently, surgical and mechanical intervention remained the principal methods for control of the multifactorial disease process. Recent advances in the development of chemotherapeutic agents have led to the increasing use of antimicrobials to suppress pathogenic flora. The use of antimetabolic agents to modulate host inflammatory response to the accumulation of bacterial plaque has also increased. Both types of chemotherapeutic agents can be used alone or in conjunction with traditional periodontal therapy to provide effective and predictable clinical improvement.

Anti-Bacterial Agents↗

PubMed1990

Sulfadiazines reduce gingivitis and plaque formation in beagle dogs.

The effect of zinc sulfadiazine (ZnSD) and silver sulfadiazine (AgSD) on reducing plaque formation and gingivitis was studied in 12 beagle dogs over a 14-week period. 12 beagle dogs were scaled, root planed and pumiced to bring them to a similar level of gingival health, prior to placing them on a diet of Purina Dog Chow softened with canned gravy and molasses to promote the build-up of plaque and the initiation of gingivitis. At the end of 8 weeks, the dogs were determined to have substantial bacterial plaque accumulation and apparent gingivitis. Thereafter, 4 dogs were treated 2 x daily with topical applications of 3% zinc sulfadiazine; 4 dogs were treated with 2% silver sulfadiazine while 4 dogs were treated with placebo gel serving as control over a 14-week treatment period. By week 2, the zinc and silver sulfadiazine dogs showed a significant decrease in gingival index which was maintained throughout the study. Additionally, by week 2, the % of sites with bleeding was also seen to decrease significantly in the experimental groups. The plaque index remained consistent in all 3 groups until week 6 when the 2 experimental groups indicated significant decrease in plaque accumulation as compared to controls. Probing depths were also seen to decrease significantly in the experimental groups after 10 weeks of therapy. The mean stain index was similar in all 3 groups of dogs throughout the study. Data indicate that both zinc and silver sulfadiazine inhibit plaque formation and reduce existing gingivitis in beagle dogs.

Administration, Topical↗

PubMed1990

Sulfadiazines prevent plaque formation and gingivitis in beagles.

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.

Administration, Topical↗

PubMed1989

A combination of platelet-derived and insulin-like growth factors enhances periodontal regeneration.

The combination of platelet-derived growth factor (PDGF) and insulin-like growth factor one (IGF-1) has previously been shown to enhance repair of soft tissue wounds. Here we report initial observations following application of PDGF and IGF-1 to periodontitis-affected teeth in beagle dogs. 1 micrograms of PDGF and IGF-1 in an aqueous gel was applied to the root surfaces of test teeth following open flap debridement. Control sites received the gel alone. Block biopsies of the teeth and surrounding bone were taken 2 weeks after treatment. Histologic analyses of control specimens revealed a long junctional epithelial attachment, and no new bone or cementum formation. In contrast, growth factor treated sites exhibited significant amounts of new bone and cementum formation. A nearly continuous layer of osteoblasts lined the newly formed bone, and there was a dense cellular "front" at the coronal extent of the new bone. These preliminary results suggest that in vivo application of the combination of PDGF and IGF-1 may enhance regeneration of the periodontal structures.

Alveolar Process↗

PubMed1989

Altering the progression of human alveolar bone loss with the non-steroidal anti-inflammatory drug flurbiprofen.

The treatment of human periodontal diseases relies on mechanical and antimicrobial suppression of the etiologic bacteria. The ability to alter the progression of periodontitis by additionally blocking host pathways involved in the destructive process is an area of current research. Prostaglandins and other metabolites of arachidonic acid are believed to be important host mediators of the bone resorption of diseases such as periodontitis. We have previously examined the effect of inhibitors of prostaglandin production, non-steroidal anti-inflammatory drugs (NSAIDs), on inhibiting alveolar bone loss in beagles. The present study was designed to examine the effect of the NSAID, flurbiprofen, on slowing the radiographic loss of alveolar bone in the human. Fifty-six individuals with radiographic evidence of alveolar bone loss were recruited for study. Forty-four patients remained in the study for the data analysis of loss of alveolar bone. Following a 6 month baseline pretreatment period to measure the radiographic progression of bone loss, half of the patients were administered flurbiprofen, 50 mg. b.i.d., while half were administered a placebo. All patients received a subgingival scaling and pumice by a hygienist every 6 months. The rate of alveolar bone loss in a 2 year treatment period was compared to the baseline 6 month pretreatment period within and between patient groups. Throughout the study, teeth exhibiting obvious loss of bone were exited from study and treated with conventional mechanical therapy. At the end of the pretreatment period both patient groups had a similar mean rate of alveolar bone loss.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1988