Increased systemic levels of inflammatory mediators following one-stage full-mouth scaling and root planing.

BACKGROUND AND OBJECTIVE: Full-mouth scaling and root planing (FM-SRP) acts as a potent inflammatory stimulus immediately after treatment; however, systemic inflammation typically improves in the long term. The contribution of FM-SRP to systemic biological and acute-phase responses is largely unknown. The purpose of this prospective intervention study was to assess the systemic and local biological responses after FM-SRP. MATERIAL AND METHODS: Thirty-one patients with generalized moderate-to-severe chronic periodontitis received 1-stage FM-SRP. Measurement of clinical parameters and body temperature as well as collection of subgingival plaque, peripheral blood and gingival crevicular fluid was performed before and after treatment 2 or 3 times. Quantification of periodontopathic bacteria in the sulcus and measurement of corresponding serum IgG titers were performed. Systemic and local inflammatory markers such as endotoxin, high-sensitive C-reactive protein (hs-CRP) and 6 inflammatory cytokines were assessed using high-sensitivity assays. RESULTS: Compared to baseline values, FM-SRP resulted in a substantial improvement in clinical parameters (P < .05), lower bacterial counts (P < .01) and a significant decrease of IgG titers against Porphyromonas gingivalis (P < .001) 6 weeks after treatment. Comparing baseline parameters to those at 1 day post-treatment, there was a statistically significant elevation in body temperature (P = .007). In addition, a 5-fold increase in hs-CRP (P < .001), a remarkable increase in interferon-γ (P < .001) and a slight increase in interleukin (IL)-12p70 (P = .001) were detected in serum samples. In the gingival crevicular fluid, marked increases in hs-CRP (P < .001), IL-5 (P = .001), IL-6, IL-12p70 and tumor necrosis factor-α (P < .001 for the latter 3 markers) were noted 1 day after treatment. Endotoxin levels were below measurable limits for most time points. CONCLUSION: FM-SRP resulted in clinical and microbiological improvement 6 weeks post-treatment, but produced a moderate systemic acute-phase response including elevated inflammatory mediators 1 day post-treatment.

Associations among tooth loss, systemic inflammation and antibody titers to periodontal pathogens in Japanese patients with cardiovascular disease.

BACKGROUND AND OBJECTIVE: It is well known that there is a strong relationship between periodontitis and cardiovascular disease (CVD). Tooth loss reflects an end-stage condition of oral diseases, such as periodontitis. Infection with specific periodontal pathogens is known as a possible factor that influences development of CVD. The aim of this study was to assess the relationship between the number of residual teeth and systemic inflammatory conditions in patients with CVD. MATERIAL AND METHODS: We divided 364 patients with CVD into four groups, according to the number of residual teeth: (i) ≥20 teeth; (ii) 10-19 teeth; (iii) 1-9 teeth; and (iv) edentulous. We recorded medical history, blood data and periodontal conditions. Serum samples were obtained and their IgG titers against three major periodontal pathogens were measured. RESULTS: Smoking rate and the prevalence of diabetes mellitus were higher in edentulous patients and in subjects with a few teeth compared with patients with many teeth. The levels of C-reactive protein were higher in patients with 1-9 teeth than in those with 10-19 teeth and with ≥20 teeth. The level of Porphyromonas gingivalis IgG in the group with 10-19 teeth was statistically higher than that in the group with ≥20 teeth. The level of P. gingivalis IgG in the edentulous group tended to be lower than that in the other groups. CONCLUSION: The patients with 1-9 teeth had the highest level of C-reactive protein among the four groups, and the patients with 10-19 teeth had the highest level of IgG to periodontal bacteria. We conclude that the number of remaining teeth may be used to estimate the severity of systemic inflammation in patients with CVD.

Assessing the progression of chronic periodontitis using subgingival pathogen levels: a 24-month prospective multicenter cohort study.

BACKGROUND: The diagnosis of the progression of periodontitis presently depends on the use of clinical symptoms (such as attachment loss) and radiographic imaging. The aim of the multicenter study described here was to evaluate the diagnostic use of the bacterial content of subgingival plaque recovered from the deepest pockets in assessing disease progression in chronic periodontitis patients. METHODS: This study consisted of a 24-month investigation of a total of 163 patients with chronic periodontitis who received trimonthly follow-up care. Subgingival plaque from the deepest pockets was recovered and assessed for bacterial content of Porphyromonas gingivalis, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans using the modified Invader PLUS assay. The corresponding serum IgG titers were measured using ELISA. Changes in clinical parameters were evaluated over the course of 24 months. The sensitivity, specificity, and prediction values were calculated and used to determine cutoff points for prediction of the progression of chronic periodontitis. RESULTS: Of the 124 individuals who completed the 24-month monitoring phase, 62 exhibited progression of periodontitis, whereas 62 demonstrated stable disease. The P. gingivalis counts of subgingival plaque from the deepest pockets was significantly associated with the progression of periodontitis (p < 0.001, positive predictive value = 0.708). CONCLUSIONS: The P. gingivalis counts of subgingival plaque from the deepest pockets may be associated with the progression of periodontitis.

Salivary pathogen and serum antibody to assess the progression of chronic periodontitis: a 24-mo prospective multicenter cohort study.

BACKGROUND AND OBJECTIVE: A diagnosis of periodontitis progression is presently limited to clinical parameters such as attachment loss and radiographic imaging. The aim of this multicenter study was to monitor disease progression in patients with chronic periodontitis during a 24-mo follow-up program and to evaluate the amount of bacteria in saliva and corresponding IgG titers in serum for determining the diagnostic usefulness of each in indicating disease progression and stability. MATERIAL AND METHODS: A total of 163 patients with chronic periodontitis who received trimonthly follow-up care were observed for 24 mo. The clinical parameters and salivary content of Porphyromonas gingivalis, Prevotella intermedia and Aggregatibacter actinomycetemcomitans were assessed using the modified Invader PLUS assay, and the corresponding serum IgG titers were measured using ELISA. The changes through 24 mo were analyzed using cut-off values calculated for each factor. One-way ANOVA or Fisher's exact test was used to perform between-group comparison for the data collected. Diagnostic values were calculated using Fisher's exact test. RESULTS: Of the 124 individuals who completed the 24-mo monitoring phase, 62 exhibited periodontitis progression, whereas 62 demonstrated stable disease. Seven patients withdrew because of acute periodontal abscess. The ratio of P. gingivalis to total bacteria and the combination of P. gingivalis counts and IgG titers against P. gingivalis were significantly related to the progression of periodontitis. The combination of P. gingivalis ratio and P. gingivalis IgG titers was significantly associated with the progression of periodontitis (p = 0.001, sensitivity = 0.339, specificity = 0.790). CONCLUSIONS: It is suggested that the combination of P. gingivalis ratio in saliva and serum IgG titers against P. gingivalis may be associated with the progression of periodontitis.

Clinical significance of antibiotic therapy in guided tissue regeneration with a resorbable membrane.

This study was designed to evaluate the clinical significance of antibiotic therapy combined with guided tissue regeneration (GTR) therapy with a collagen membrane. The subjects were 20 adults diagnosed with periodontitis (20 intrabony periodontal defects). Ten patients were treated with GTR alone (control group) and the other 10 patients were treated with a combination of GTR and antibiotics (antibiotic group). In the antibiotic group, minocycline ointment was applied locally before GTR therapy, and doxycycline and amoxyline were systemically administered after GTR therapy. Clinical manifestations, the presence or absence of exposed membrane, and microbiological findings were assessed 1 month before, immediately after, and 2 weeks, 6 weeks, and 3 months after GTR therapy. The results showed no significant differences in reduction of probing depth, probing attachment gain (PAG), or the ratio of PAG to intraoperative depth of the intrabony defect (vertical relative attachment gain) between the antibiotic group and the control group before and 3 months after GTR therapy. A DNA probe test and specific enzymatic activity test revealed no significant differences in the improvement and the rate of bacterial negativity before, and 6 weeks and 3 months after, GTR therapy. These findings indicate that antibiotic therapy is not clinically beneficial when combined with GTR therapy with a collagen membrane.

Intra-pocket antibiotic therapy using resorbable and non-resorbable slow-release devices containing tetracycline.

Since it is a disease mainly caused by plaque--an aggregate of various bacteria--periodontal disease can be considered a local infection. Thus, it has seemed reasonable to utilize antibiotics to suppress the intrapocket bacteria, specifically or nonspecifically. When antibiotics are administered orally, however, massive doses over a prolonged period of time are needed to attain a therapeutic effect. This increases the risk of adverse reactions as well as developing resistant strains of bacteria. To overcome these problems, local drug delivery systems (LDDS) were devised to combat the local infection. However, the intrapocket antibiotic delivery systems have yet to be fully evaluated for clinical effectiveness; to prove the therapeutic effectiveness of locally administered antibiotics, the drug must reach the base of the periodontal pocket and the effective concentration of the antibiotic against the pathogenic bacteria must be maintained for a long time. This concise review presents with figures, tables, and a comprehensive list of references the many studies which have used the various tetracyclines as LDDS to treat periodontal disease.

The effect of root conditioning with minocycline HCl in removing endotoxin from the roots of periodontally-involved teeth.

Noting the acid-conditioning effect of minocycline on the root surface, we investigated the ability of minocycline to remove endotoxin on untreated, diseased cementum in vitro. Root surface specimens affected by periodontal disease were immersed in minocycline solution (10 mg/ml, 50 micrograms/ml, and 5 micrograms/ml) for 10 minutes, 1 day, 3 days, and 7 days, and endotoxin eluted was determined by the limulus amoebocyte lysate (LAL) assay. Specimens serving as controls were treated by immersion in pyrogen-free water, agitation, polishing, or exposure to citric acid (pH 1.0) for 3 minutes. When the period of immersion was the same, the root treatment with minocycline (10 mg/ml) yielded a significantly higher rate of neutralization of endotoxin than that with a 5 micrograms/ml or 50 micrograms/ml solution. However, the detoxifying effect of this method was less adequate than that of polishing or treatment with citric acid solution. There was variability in the effects of polishing among the teeth tested. To obtain the expected effect of the root treatment with minocycline solution; i.e., removal of the endotoxin, the combining of minocycline with a mechanical root preparation, such as polishing or root planing, seems to be effective.

Therapeutic effects of combined treatment using tetracycline-immobilized collagen film and root planing in periodontal furcation pockets.

46 upper and lower molars with furcation grade II involvement were selected from 16 patients with periodontal disease. The teeth were randomly allocated to the following groups according to treatment; (1) 4 consecutive administrations of tetracycline-immobilized cross-linked collagen film (TC film) at intervals of 1 week (TC group); (2) 1 root planing treatment (RP group); (3) combination treatment (TC + RP group); (4) no treatment (control group). The therapeutic effects of each treatment were compared both clinically and microbiologically. Records of plaque index, gingival index, bleeding on probing, probing depth, probing attachment level and microscopic counts were obtained at 0, 4, 6 and 8 weeks. The results showed marked decreases in probing depth and density of micro-organisms in both the RP and TC + RP groups. In particular, the TC + RP group was characterized by a decreased rate of bleeding on pocket probing and an increased probing attachment gain. The above findings demonstrated that root planning is effective in the treatment of furcation involvement and that the effects are enhanced by the local administration of TC films.

A critical review of the biologic rationale for guided tissue regeneration.

This review discusses the rationale for using guided tissue regeneration therapy. The review not only attempts to clarify the concept of selective tissue regeneration using non-resorbable and resorbable barriers, but to discuss differences in healing events after treatment with the two types of barriers together with their significance in periodontal therapy. At present, barrier membranes have potential clinical use in promoting periodontal tissue regeneration if patients to be so treated are selected appropriately. Research is still necessary to determine the critical period for guiding the ingrowth of new attachment forming cells and also to further clarify the concept of GTR involving the "wrong cell type" which inhibits periodontal tissue regeneration.

[Regeneration of the rat submandibular glands after duct ligation].

The cytomorphologic changes associated with acinar cell recovery in the rat submandibular glands were examined by light and electron microscopic observation and immunohistochemical test using anti-bromodeoxyuridine antibody. Ligation of excretory ducts caused morphological disorganization of the gland parenchyma, with resultant disappearance of the acini, dilation of the ducts, pronounced fibrosis and infiltration of the inflammatory cells. At seven days after obstruction, the acinar cells shrunk and destroyed partly. However, the intercalated duct cells and the myoepithelial cells were unaffected by ligation. Immunohistochemically, bromodeoxyuridine (BrdU) labeled cells existed scatteringly in the original ducts through the period of duct ligation and unligation studied. In the glands after recanalization following 7 days of the duct ligation, the duct-like structures were recognized a progressive increase. There structures were significantly developed in number from 7 to 14 days after the unligation. However, the BrdU-containing nuclei were not almost found in the duct-like structures. At twenty one days after the removal of the obstruction, the regeneration of acinar cells was striking. At 28 days, the acini were almost normal size. In the unligated glands at 21 and 28 days, a variable number of BrdU-positive cells was found in acini. At this stage, the constituent cells of the duct-like structures occurred many vacuoles and a decrease in their secretory granules was marked. These cells were transformed into intercalated duct cells. These results suggest that the constituent cells of the duct-like structures are altered for intercalated duct cells. The regeneration of acinar cells is the result of cell recovery, not the result of de novo cell differentiation.

Subgingival administration of tetracycline on a collagen film.

The purpose of this study was to evaluate the duration of therapeutic effect after administration of the collagen film immobilized tetracycline (TC film). TC film or tetracycline non-immobilized placebo film was applied one time to the periodontal pocket (greater than or equal to 4 mm) of five periodontitis patients (20 teeth). The clinical and microbiological effects are summarized as follows: The group that received TC film continued to show significantly low values for bleeding upon probing the pocket depth for 3 and 4 weeks, respectively, after administration, but there was no significant difference in the plaque index or gingival index when compared with the group that received a placebo film. In the TC film group, the density of microorganisms and the proportion of motile rods and spirochetes were also significantly decreased 3 weeks after administration. These findings suggest that topically administered TC film remains both clinically and bacteriologically effective for 2 to 3 weeks.

Effects of atelocollagen on the wound healing reaction following palatal gingivectomy in rats.

Collagen membrane preparations have been manufactured with the aim of enhancing wound healing following periodontal surgery. After cross-linking by various processing methods (with ultraviolet radiation or hexamethylenediisocyanate) and to various extents, atelocollagen membranes were applied into dissection sites within palatal gingival tissue. Applied atelocollagen was histopathologically compared with applied lyophilized porcine dermis (LPD) and controls in rats, with regard to the time course of healing. The atelocollagen-applied group showed more satisfactory regeneration of the epithelium and connective tissue in an artificially created gingival defect than did the control group or the LPD-applied group. Epithelial downgrowth along the root surface was significantly suppressed by the use of atelocollagen. In addition, the post-operative inflammatory reaction and foreign body giant cell reaction subsided rapidly after surgery in the atelocollgen-applied group. Our results show that the use of atelocollagen membrane in periodontal wounds should be the method of choice.

Clinical effects of local application of collagen film-immobilized tetracycline.

Tetracycline-containing cross-linked collagen film (TC film), or tetracycline-free placebo film, were locally applied 4 times, at 1-week intervals, to 33 teeth with periodontal pockets larger than 4 mm, in 11 patients with periodontal disease. The clinical and microbiological effects are summarized, as follows. In the group treated with the TC film, (1) the clinical indices were significantly decreased at the 4th and 7th weeks in comparison with those at the beginning of treatment. In particular, this group showed a significant decrease in the incidence of bleeding as compared with the placebo group at the 4th week. (2) Total counts of bacteria in the periodontal pockets showed an obvious tendency to decrease with time. The proportion of black-pigmented bacteroides was significantly decreased at the 4th and 7th weeks when compared with the pretreatment value. The extent of decrease in the proportion of spirochetes at both the 4th and 7th weeks was significant compared with the placebo group and the pretreatment value.

The effect of various concentrations of collagen barrier on periodontal wound healing.

Collagen membrane preparations were manufactured with the aim of enhancing wound healing following periodontal surgery. In order to clarify effects of different concentrations of collagen on wound healing, a basic study was performed. Solutions containing 0.5%, 1.0%, and 1.3% atelocollagen were treated with hexamethylenediisocyanate (HMDIC) for cross-linking, and collagen membranes were prepared with each solution. Periodontal flap surgery was performed on the palatal gingiva beside the maxillary first molar teeth in rats. The root surface of the tooth was exposed and curretted. Then, a piece of atelocollagen membrane was implanted. The healing of the wound was studied histologically and the following findings were made. (1) Apical migration of the junctional epithelium occurred within 2 weeks postoperatively. (2) The implantation of atelocollagen membrane significantly reduced the apical migration. (3) The apical migration of the epithelium did not vary with collagen concentration.

[Application of local drug delivery system to periodontal therapy. 4. Comparison of the therapeutic effects of administration of a TC film or root debridement on human periodontal disease].

In 8 patients with periodontal diseases under good supragingival plaque control, 22 test teeth each having a pocket not more than 4 mm deep were treated respectively with 3 consecutive administrations of tetracycline immobilized cross-linked collagen film (TC film) at intervals of 1 week, with onceroot planing and with both of these. The therapeutic effects were compared both clinically and micro biologically. The results revealed improvements in clinical symptoms such as reduction in the depth of the pocket, bleeding on pocket probing and the like for each treatment group in 6-12 weeks. The second and third groups also showed remarked gingival recession. Further more, the density of intrapocket microorganisms showed a remarked decrease up to the 8th week for each treatment group and the population of spirochetes showed a decrease up to the 6th week for the first treatment group and up to the 8th-12th week for the second and third treatment group. The results show that both local application of the TC film and root planing are effective in periodontal treatment, but not the combined treatment.