Microbiological and Clinical Effects of Sitafloxacin and Azithromycin in Periodontitis Patients Receiving Supportive Periodontal Therapy.

Sitafloxacin (STFX) is a newly developed quinolone that has robust antimicrobial activity against periodontopathic bacteria. We previously reported that oral administration of STFX during supportive periodontal therapy was as effective as conventional mechanical debridement under local anesthesia microbiologically and clinically for 3 months. The aim of the present study was to examine the short-term and long-term microbiological and clinical effects of systemic STFX and azithromycin (AZM) on active periodontal pockets during supportive periodontal therapy. Fifty-one patients receiving supportive periodontal therapy were randomly allocated to the STFX group (200 mg/day of STFX for 5 days) or the AZM group (500 mg/day of AZM for 3 days). The microbiological and clinical parameters were examined until 12 months after the systemic administration of each drug. The concentration of each drug in periodontal pockets and the antimicrobial susceptibility of clinical isolates were also analyzed. The proportions of red complex bacteria, i.e., Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia, which are the representative periodontopathic bacteria, were significantly reduced at 1 month and remained lower at 12 months than those at baseline in both the STFX and AZM groups. Clinical parameters were significantly improved over the 12-month period in both groups. An increase in the MIC of AZM against clinical isolates was observed in the AZM group. These results indicate that monotherapy with systemic STFX and AZM might be an alternative treatment during supportive periodontal therapy in patients for whom invasive mechanical treatment is inappropriate. (This study has been registered with the University Hospital Medical Information Network-Clinical Trials Registry [UMIN-CTR] under registration number UMIN000007834.).

Effects of systemic sitafloxacin on periodontal infection control in elderly patients.

OBJECTIVE: To evaluate the microbiological and clinical effects of the systemic administration of sitafloxacin (STFX) on periodontal pockets in elderly patients receiving supportive periodontal therapy (SPT). BACKGROUND: Periodontitis is a risk factor for atherosclerosis. Better periodontal health contributes to reduce atherosclerosis-related diseases in elderly population. MATERIALS AND METHODS: Forty-four patients undergoing SPT were randomly assigned to two groups: a test group took 100 mg/day of STFX for five consecutive days, or a control group received scaling and root planing (SRP) under local anaesthesia. Microbiological and clinical parameters were examined at baseline and at 1 and 3 months after therapy. RESULTS: The presence of Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia was significantly reduced at 1 month after treatment in both groups. The median reductions of the bacteria between the baseline and 1 month were 3.08 and 2.54% in the STFX- and SRP-treated groups, respectively. Both treatments significantly decreased the probing depth at 1 and 3 months compared to the baseline. CONCLUSION: The systemic administration of STFX is effective at improving periodontal health during SPT and could be an alternative to SRP for elderly patients who cannot undergo anaesthesia or are at risk of tissue injury.

Elevated expression of IL-17 and IL-12 genes in chronic inflammatory periodontal disease.

BACKGROUND: A number of different theories have been postulated to explain the progression of gingivitis to periodontitis in the context of the Th1/Th2 paradigm. However, no consistent results have been obtained. Th17, a new T-cell subset producing IL-17, which is implicated in many aspect of inflammatory tissue destruction, overcomes many of the discrepant findings in the studies related to the Th1/Th2 hypothesis. We compared the gene expression profile of Th17-related molecules in gingivitis and periodontitis lesions showing distinct clinical entities. METHODS: Gingival tissue samples were obtained from 23 gingivitis and 24 periodontitis tissues. The gene expression was measured by using quantitative real-time PCR for IL-17A, IL-17F, CCR4, CCR6, IL-12 p35 and IL-23 p19. The difference of gene expressions between gingivitis and periodontitis was analyzed by Mann-Whitney U-test. Correlations between each gene expression were also analyzed. RESULTS: The expression level of IL-17A was higher than that of IL-17F and a significant difference in expression between gingivitis and periodontitis was observed only for IL-17A. CCR4 and CCR6 tended to be higher in periodontitis compared with gingivitis, although the differences were not statistically significant. Whereas the gene expression of IL-12 p35 was significantly higher in periodontitis compared with gingivitis, that of IL-23 p19 was not different between the two diseases. CONCLUSION: This study demonstrates the elevated expression of IL-17 and IL-12 in periodontitis, i.e., the tissue destruction form of periodontal diseases, as compared with gingivitis, and provides new insight into the T-cell mediated immunopathogenesis of periodontal disease.

Single-strand conformation polymorphism analysis for the diagnosis of T-cell clonality in periodontal disease.

T cells recognize antigens via the T-cell receptor (TCR). Diversity in antigen recognition by T cells is generated in part by the recombination of V, (D), J, and C segments of the TCR. It is further enhanced by the N region, in addition to non-germline-encoded nucleotides at the V-(D)-J junction. It is generally believed that each T cell bears a distinct clonotype of TCR and that each clonotype is responsible for an antigen-specific T-cell response. T-cell clonal expansion has been detected in the peripheral blood or the disease-affected sites in patients with infections, autoimmune diseases, malignancy, and post-transplantation complications. Since antigen stimulation of T cells induces the proliferation of specific T cells, clonal T-cell expansion is considered to be a result of an antigen-specific immune response. For the analysis of such antigen-specific T cells, it is common to use their specific antigens if they are known. However, there are many diseases, such as periodontal diseases, in which there are a number of putative pathogenic antigens involved. In these circumstances, the detection of clonally expanded T cells is an effective method to evaluate whether antigen-specific immune responses are involved, since only a few clonally expanded T cells are detected in healthy individuals. In addition, the characterization of any clonally expanded T cells that are detected would further promote the understanding of the disease mechanisms. By using single-strand conformation polymorphism (SSCP) analysis, we demonstrated that oligoclonal T-cell accumulation was present in periodontitis lesions, in contrast to a heterogeneous T-cell population in the peripheral blood. SSCP is a powerful tool for analyzing specific T-cell responses both in vitro and in vivo.

Accumulation of human heat shock protein 60-reactive T cells in the gingival tissues of periodontitis patients.

Heat shock protein 60s (hsp60) are remarkably immunogenic, and both T-cell and antibody responses to hsp60 have been reported in various inflammatory conditions. To clarify the role of hsp60 in T-cell responses in periodontitis, we examined the proliferative response of peripheral blood mononuclear cells (PBMC), as well as the cytokine profile and T-cell clonality, for periodontitis patients and controls following stimulation with recombinant human hsp60 and Porphyromonas gingivalis GroEL. To confirm the infiltration of hsp60-reactive T-cell clones into periodontitis lesions, nucleotide sequences within complementarity-determining region 3 of the T-cell receptor (TCR) beta-chain were compared between hsp60-reactive peripheral blood T cells and periodontitis lesion-infiltrating T cells. Periodontitis patients demonstrated significantly higher proliferative responses of PBMC to human hsp60, but not to P. gingivalis GroEL, than control subjects. The response was inhibited by anti-major histocompatibility complex class II antibodies. Analysis of the nucleotide sequences of the TCR demonstrated that human hsp60-reactive T-cell clones and periodontitis lesion-infiltrating T cells have the same receptors, suggesting that hsp60-reactive T cells accumulate in periodontitis lesions. Analysis of the cytokine profile demonstrated that hsp60-reactive PBMC produced significant levels of gamma interferon (IFN-gamma) in periodontitis patients, whereas P. gingivalis GroEL did not induce any skewing toward a type1 or type2 cytokine profile. In control subjects no significant expression of IFN-gamma or interleukin 4 was induced. These results suggest that periodontitis patients have human hsp60-reactive T cells with a type 1 cytokine profile in their peripheral blood T-cell pools.