Differential chemokine response of fibroblast subtypes to complement C1q.

BACKGROUND AND OBJECTIVE: The pathogenesis of periodontitis includes an inappropriate activation of the classical complement cascade (C') with accumulation of inflammatory C' products in fluids and tissues. Our hypothesis is that in vivo the C' product, C1q, may act as a regulatory component of the innate immune response of distinct matrix fibroblasts to the inflammatory environment. This study analyzed the C1q induction of pro-inflammatory cytokine secretion in fibroblast subtypes derived from distinct periodontal tissues, and identified a mechanism of the cell response. MATERIAL AND METHODS: Primary human gingival fibroblast, periodontal ligament fibroblast, and granulation tissue fibroblast cultures were treated for 24 h with C1q. Protein arrays assessed the secretory profile of constitutive and C1q-inducible pro-inflammatory cytokines, and enzyme-linked immunosorbent assays were used to quantify the kinetics of each inducible cytokine. RESULTS: Granulation tissue fibroblast cultures were unresponsive to C1q challenge. In contrast, periodontal ligament fibroblasts responded with a release of monocyte chemoattractant protein (MCP)-1, interleukin-6, interleukin-8, and macrophage inflammatory protein (MIP)-1beta higher than the basal level by 8.2-, 7.0-, 3.8-, and 7.2-fold, respectively. Human gingival fibroblast cultures increased secretion of these chemokines by 5.2-, 4.5-, 3.0-, and 9.8-fold, respectively. Inhibitor studies revealed that C1q-inducible release of chemokines by the human gingival fibroblast and periodontal ligament cultures was contingent upon p38 mitogen-activated protein kinase activity. CONCLUSION: The ability of C1q to stimulate secretion of pro-inflammatory chemokines depends upon which specific fibroblast subtype is involved. Targeting C1q-activated intracellular signaling pathways may be an effective means to inhibit the production of chemokines that promote inflammatory cell infiltration into gingival and periodontal ligament tissues.

The effectiveness of virtual reality for dental pain control: a case study.

The present study explored whether immersive virtual reality can serve as an effective non-pharmacologic analgesic for dental pain. Two patients (aged 51 and 56 years old) with adult periodontitis, a chronic, progressive inflammatory disease that affects gums, ligaments, and bones around the teeth, were studied in the treatment room of a periodontist. Each patient received periodontal scaling and root planing (scraping off/removing plaque deposits below the gum line, hereafter referred to as scaling) under three treatment conditions: (1) virtual reality distraction, (2) movie distraction, and (3) a no-distraction control condition. Condition order was randomized and counterbalanced. For each of the three treatment conditions, five visual analog pain scores for each treatment condition served as the dependent variables. On 0-10 labeled scales, both patients provided sensory and affective pain ratings, and subjective estimates of time spent thinking about his pain during the procedure. For patient 1, mean pain ratings were in the severe range while watching a movie (7.2), or no distraction (7.2) but in the mild pain range (1.2) during the VR condition. Patient 2 reported mild to moderate pain with no distraction (mean = 4.4), mild pain while watching the movie (3.3), and essentially no pain while in VR (0.6) during his periodontal scaling. Although the small sample size limits generalizability, we contend that virtual reality is a uniquely attention-grabbing medium capable of maximizing the amount of attention drawn away from the "real world," allowing patients to tolerate painful dental procedures. These preliminary results suggest that immersive VR merits more attention as a potentially viable adjunctive nonpharmacologic analgesia for procedural dental/periodontal pain. Virtual reality may also have analgesic potential for other painful procedures or pain populations. Practical implications are discussed.

Immunolocalization of platelet-derived growth factor A and B chains and PDGF-alpha and beta receptors in human gingival wounds.

Platelet-derived growth factor (PDGF) is a polypeptide growth factor which has been implicated as a major mitogen involved in wound healing. The PDGF appears to promote periodontal regeneration; however, its distribution in gingival tissues is not known and how it participates in gingival wound healing is unclear. Using highly specific antibodies we have studied the distribution of PDGF A and B chains and alpha- and beta-PDGF receptors in healing human gingival wounds. Wounds were created by making a 0.75 mm deep incision in the papilla and healthy gingiva and biopsies were obtained from the same site after 8 h and 1, 3, 7, 14 and 21 d. Frozen sections were immunostained with affinity purified antibodies. The results showed that both epithelium and fibrin clot manifested positive immunostaining for anti-PDGF-A and B-chain antibodies. Staining was present in unwounded and wounded epithelia, and in the fibrin clot it appeared to be more intense for the PDGF-A chain. Blood vessels in connective tissue were also positive while other areas were largely negative. No significant staining was detectable in healthy tissues for anti-PDGF-alpha or -beta receptor antibodies. However, the wound site began to manifest positive immunostaining fro anti-beta-receptor antibody after 3 d of healing, became maximal at 7 d, and then decreased. Our data indicate, but do not prove, that gingival epithelium may be a source of PDGF A and B chains and that the A chain may have a more prominent role to play during early stages of healing. Expression of PDGF beta-receptor appears later at the wound site, indicating that the PDGF B isomer may regulate later wound healing events.

Treatment of gingivitis and periodontitis. Research, Science and Therapy Committee of the American Academy of Periodontology.

This paper is one of three in a series prepared by the Research, Science and Therapy Committee of The American Academy of Periodontology and is intended for the information of the dental profession. It represents the position of the Academy regarding the current state of knowledge about treatment of gingivitis and periodontitis. The other papers are entitled The Etiology and Pathogenesis of Periodontal Diseases and Diagnosis of Periodontal Diseases.

Long-term evaluation of root-resected molars: a retrospective study.

Thirty-two consecutively treated patients were included in this study of 49 root-resected molars that were under regular recall of 3 to 6 months for a mean of 11.5 years (2 to 23 years). Treatment modalities for all patients were very similar. Endodontic treatment was conservatively performed prior to resection with maximum preservation of tooth structure. No threaded posts were used. Provisional restorations were in place prior to periodontal therapy (pocket reduction with or without osseous surgery). Most patients were treated with complete-mouth reconstructions. Ninety-two percent of all resected molars survived an average of 12 years. Teeth failed because of recurrent caries or for endodontic and strategic reasons. If proper treatment is rendered periodontically involved molars can be maintained for a long period of time and serve successfully as abutments in complete-mouth restorations. Great care must be taken throughout the whole process of case selection, reevaluation, and endodontic, periodontal, restorative, and maintenance therapies.

Effects of antibiotic treatment on clinical conditions with guided tissue regeneration: one-year results.

The one-year results of a regenerative procedure in patients treated with or without antibiotics are presented. Expanded polytetrafluoroethylene (ePTFE) was placed over mandibular molar Class II furcation invasions and retained for four weeks. The patients in group 1 received no antibiotics; patients in group 2 received amoxicillin/clavulanate potassium during the first 10 post-operative days. The initial differences in tested microorganisms and post-surgical inflammation indicated that the use of the antibiotic might enhance the long-term outcome. After one year, the reduction in mean probing depth of the furcation invasions was 2.0 +/- 1.2 mm for group 1 and 1.8 +/- 1.1 mm for group 2. An overall gain of 0.8 mm of clinical attachment was found. Twenty-two of the 24 sites were re-entered. Wide individual variations were found but the changes between pre-treatment and one-year data for any of 6 linear measurements of hard tissue landmarks did not differ between groups or between pre-treatment and re-entry. A combination of an overall loss of 0.4 mm alveolar bone at the crest and 0.3 mm gain of bone at the bottom of the furcation defects was found. Volumetric analysis indicated an average 32% bone fill for both groups, ranging from a decrease in defect volume by 84% (gain) to an increase of the size of the furcation invasion by 66% (loss). A decrease in defect volume > 30% was found at 7 sites from each group. The antibiotic may have controlled initial inflammation, but 12 months later it had no direct effect on bone regeneration or soft tissue attachment.

Effects of antibiotic treatment on clinical conditions and bacterial growth with guided tissue regeneration.

Mucogingival flaps were reflected over pairs of mandibular molar teeth with Class II furcation invasions. The dimensions of the furcations were measured. The teeth were debrided and an expanded polytetrafluoroethylene (e-PTFE) membrane was placed and retained over one furcation of each pair (test site) for 4 weeks. The second site served as a control. Eight patients (group 1) with 12 e-PTFE sites received no antibiotic. Seven patients (group 2) with 12 e-PTFE sites were administered amoxicillin/clavulanate potassium for 10 days. Paper-points were used to collect bacterial samples and clinical indices were recorded at baseline and weekly for 4 weeks. Paper-point samples and the e-PTFE collected at week 4 were sonicated and analyzed by DNA probes for seven putative pathogens. At baseline no parameter showed statistical differences between groups or sites. At week 1 significantly greater levels of Prevotella intermedia type I (P < 0.05) and Fusobacterium nucleatum (P < 0.01) were found in group 1. At week 4, paper-point samples from test sites (P < 0.05) and e-PTFE materials (P < 0.001) showed significantly higher presence of Bacteroides forsythus in group 1. No significant microbial changes were found for control sites over time or between groups. The total bacterial load at test sites over time increased similarly for patients administered or not administered the antibiotic. Clinical signs of inflammation were significantly greater in group 1 and associated with the presence of B. forsythus (P < 0.01).

Periodontal repair after surgical debridement with and without cartilage allografts.

The effect of a cartilage allograft on healing in intrabony defects treated by open flap curettage was investigated at 130 surgical sites in 4 patients. Thinned mucoperiosteal flaps were elevated and the intrabony defects were debrided. A stent with stainless steel pins was used to measure defect depth at fixed locations adjacent to the root surfaces. The bony defects treated ranged from 0-9 mm with a mean intraosseous depth of 2.4 mm. 62 sites received cartilage implants and 68 sites were treated by surgical debridement only. The flaps were readapted and sutured to the level of the alveolar crest. After 16 weeks the defects were remeasured. Both treatment methods resulted in a mean apical shift of -0.09 mm of the base of the defects that were less than 3 mm and a mean coronal shift of 0.9 mm in defects that were greater than 3.5 mm in depth. The repair in deeper lesions increased with the number of intrabony walls. Mean pocket depth at flap curettage sites was reduced from 5.4-3.3 mm (P less than 0.01) at 16 weeks. At sites receiving the cartilage, the mean pocket depth decreased from 5.6-3.6 mm (P less than 0.01). Pocket reduction resulted from a combination of surgical recession and a mean gain of 1 mm in clinical attachment (P less than 0.05 for flap curettage sites only). The cartilage implants provided no statistically significant advantage in either bony or soft tissue repair over flap debridement alone. Although bony repair is influenced by depth and configuration of the intrabony defects, significant gains in attachment and reductions in pocket depth may occur independently of changes at the base of the intrabony defects.

A longitudinal study of peridontal status comparing osseous recontouring with flap curettage. I. Results after 6 months.

The purpose this study was to test for short-term clinical differences in periodontal status after treatment with osseous recontouring and flap curettage in humans. Twelve systemically healthy patients with bilaterally similar marginal periodontal destruction received a standardized regime of presurgical therapy. The posterior segments of these patients were then treated with osseous recontouring and flap curettage. The investigators assigned the segments in one jaw at random to osseous recontouring and flap curettage, and then reversed the sides receiving surgical treatment in the opposing jaw. Postsurgical photographs and measurements for supragingival plaque, tooth mobility, gingival inflammation and periodontal attachment levels relative to the cemento-enamel junction were made for 6 months. Statistical analysis revealed that: (1) osseous recontouring and open flap curettage equally reduced plaque and gingival inflammation; (2) each surgical procedure equally increased attached gingiva; (3) pocket reduction achieved with osseous recontouring was maintained over 6 months, pockets recurring after open curettage; (4) open curettage did not induce bone regeneration; (5) osseous recontouring did not result in irreversible tooth mobility; (6) osseous recontouring resulted in a net loss of attachment; open curettage producing a net gain, especially in deeper pockets; and (7) both procedures improved periodontal health.

The effect of splinting on tooth mobility. (2) After osseous surgery.

The purpose of this study was to determine if fixed splinting of teeth with intraoral wire and acrylic splints had advantages with respect to tooth mobility, bone level and attachment level over unsplinted teeth following osseous surgery. Ten patients were chosen who exhibited bilaterally similar chronic destructive periodontitis and mobile teeth. One maxillary sextant was splinted, while the other was unsplinted. Both sextants functioned against an unsplinted mandibular arch. Following initial therapy, osseous surgery was performed in both maxillary sextants on the same day. Tooth mobility data was collected 1 week before and at 3, 6, 12, and 24 weeks following surgery. Levels of gingival attachment and bone were recorded before and 24 weeks after surgery. Splints were removed before measurements, then replaced, and the occlusion refined. Prophylaxes and oral hygiene instruction were repeated every 3 weeks throughout the study. For all categories of teeth and mobility examined, tooth mobility increased initially after surgery and subsequently decreased by 24 weeks to about presurgical values. The splinted and unsplinted segments reacted similarly throughout the study; splinting did not significantly reduce the mobility of individual teeth. Pre- and postsurgical bone and gingival attachment levels were also similar for the splinted and unsplinted segments.