Takao Hirofuji

FGF-2 Stimulates Periodontal Regeneration Results of a Multi-center Randomized Clinical Trial

The efficacy of the local application of recombinant human fibroblast growth factor-2 (FGF-2) in periodontal regeneration has been investigated. In this study, a randomized, double-blind, placebo-controlled clinical trial was conducted in 253 adult patients with periodontitis. Modified Widman periodontal surgery was performed, during which 200 µL of the investigational formulation containing 0% (vehicle alone), 0.2%, 0.3%, or 0.4% FGF-2 was administered to 2- or 3-walled vertical bone defects. Each dose of FGF-2 showed significant superiority over vehicle alone (p < 0.01) for the percentage of bone fill at 36 wks after administration, and the percentage peaked in the 0.3% FGF-2 group. No significant differences among groups were observed in clinical attachment regained, scoring approximately 2 mm. No clinical safety problems, including an abnormal increase in alveolar bone or ankylosis, were identified. These results strongly suggest that topical application of FGF-2 can be efficacious in the regeneration of human periodontal tissue that has been destroyed by periodontitis.

Periodontal tissue regeneration using fibroblast growth factor -2:Randomized controlled phase II clinical trial

Background The options for medical use of signaling molecules as stimulators of tissue regeneration are currently limited. Preclinical evidence suggests that fibroblast growth factor (FGF)-2 can promote periodontal regeneration. This study aimed to clarify the activity of FGF-2 in stimulating regeneration of periodontal tissue lost by periodontitis and to evaluate the safety of such stimulation. Methodology/Principal Findings We used recombinant human FGF-2 with 3% hydroxypropylcellulose (HPC) as vehicle and conducted a randomized double-blinded controlled trial involving 13 facilities. Subjects comprised 74 patients displaying a 2- or 3-walled vertical bone defect as measured ≥3 mm apical to the bone crest. Patients were randomly assigned to 4 groups: Group P, given HPC with no FGF-2; Group L, given HPC containing 0.03% FGF-2; Group M, given HPC containing 0.1% FGF-2; and Group H, given HPC containing 0.3% FGF-2. Each patient underwent flap operation during which we administered 200 µL of the appropriate investigational drug to the bone defect. Before and for 36 weeks following administration, patients underwent periodontal tissue inspections and standardized radiography of the region under investigation. As a result, a significant difference (p = 0.021) in rate of increase in alveolar bone height was identified between Group P (23.92%) and Group H (58.62%) at 36 weeks. The linear increase in alveolar bone height at 36 weeks in Group P and H was 0.95 mm and 1.85 mm, respectively (p = 0.132). No serious adverse events attributable to the investigational drug were identified. Conclusions Although no statistically significant differences were noted for gains in clinical attachment level and alveolar bone gain for FGF-2 groups versus Group P, the significant difference in rate of increase in alveolar bone height (p = 0.021) between Groups P and H at 36 weeks suggests that some efficacy could be expected from FGF-2 in stimulating regeneration of periodontal tissue in patients with periodontitis. Trial Registration ClinicalTrials.gov NCT00514657

Effects of probiotic Lactobacillus salivarius WB21 on halitosis and oral health: an open-label pilot trial.

OBJECTIVE The objective of this study was to evaluate whether oral administration of lactobacilli alters the degree of halitosis and clinical conditions associated with halitosis. STUDY DESIGN Twenty patients with genuine halitosis were given 2.0 x 10(9)Lactobacillus salivarius WB21 and xylitol in tablet form daily. Oral malodor and clinical parameters were evaluated at the same time of day for each patient after 2 and 4 weeks. RESULTS All 20 patients were positive for L. salivarius DNA in their saliva at 2 weeks, although 12 patients were negative for this organism at baseline. Oral malodor parameters significantly decreased at 2 weeks in the subjects with physiologic halitosis. The scores of an organoleptic test and bleeding on probing significantly decreased at 4 weeks in the subjects with oral pathologic halitosis. CONCLUSIONS Oral administration of probiotic lactobacilli primarily improved physiologic halitosis and also showed beneficial effects on bleeding on probing from the periodontal pocket.

Detection of Helicobacter pylori DNA in the saliva of patients complaining of halitosis

Helicobacter pylori infection, which causes peptic ulcers and gastric cancer, is considered a possible cause of halitosis. Recently, the oral cavity was identified as a possible H. pylori reservoir, particularly in the presence of periodontal disease, which is a cause of halitosis. The purpose of this study was to evaluate by PCR the prevalence of oral H. pylori in the saliva of subjects complaining of halitosis. Samples were obtained from 326 non-dyspeptic subjects, comprising 251 subjects with actual malodour and 75 subjects without halitosis. DNA was extracted from the samples, and the presence of H. pylori and periodontopathic bacteria including Porphyromonas gingivalis, Treponema denticola and Prevotella intermedia was examined by PCR. H. pylori was detected in 21 (6.4 %) of 326 samples. The methyl mercaptan concentration and periodontal parameters including tooth mobility, periodontal pocket depth (PPD) and occult blood in the saliva were significantly greater in the H. pylori-positive subjects. Each of the periodontopathic bacteria was also detected at a significantly higher frequency in the H. pylori-positive subjects. Among those patients with a PPD of > or =5 mm and a tongue coating score of < or =2, no difference was observed in oral malodour levels between the H. pylori-positive and -negative subjects. However, the presence of occult blood in the saliva and the prevalence of Prevotella intermedia were significantly greater in the H. pylori-positive subjects. H. pylori was detected in 16 (15.7 %) of 102 subjects with periodontitis, suggesting that progression of periodontal pocket and inflammation may favour colonization by this species and that H. pylori infection may be indirectly associated with oral pathological halitosis following periodontitis.

Relationship between Oral Malodor and the Global Composition of Indigenous Bacterial Populations in Saliva

ABSTRACT Oral malodor develops mostly from the metabolic activities of indigenous bacterial populations within the oral cavity, but whether healthy or oral malodor-related patterns of the global bacterial composition exist remains unclear. In this study, the bacterial compositions in the saliva of 240 subjects complaining of oral malodor were divided into groups based on terminal-restriction fragment length polymorphism (T-RFLP) profiles using hierarchical cluster analysis, and the patterns of the microbial community composition of those exhibiting higher and lower malodor were explored. Four types of bacterial community compositions were detected (clusters I, II, III, and IV). Two parameters for measuring oral malodor intensity (the concentration of volatile sulfur compounds in mouth air and the organoleptic score) were noticeably lower in cluster I than in the other clusters. Using multivariate analysis, the differences in the levels of oral malodor were significant after adjustment for potential confounding factors such as total bacterial count, mean periodontal pocket depth, and tongue coating score (P < 0.001). Among the four clusters with different proportions of indigenous members, the T-RFLP profiles of cluster I were implicated as the bacterial populations with higher proportions of Streptococcus, Granulicatella, Rothia, and Treponema species than those of the other clusters. These results clearly correlate the global composition of indigenous bacterial populations with the severity of oral malodor.

Relationship between halitosis and psychologic status

OBJECTIVE To examine the psychosomatic aspects of patients complaining of halitosis. STUDY DESIGN Breath malodor in 165 patients was measured using an organoleptic test (OLT), sulfide monitoring, and gas chromatography. Clinical evaluation included oral examination, OLT, and volatile sulfur compound measurement. The psychologic condition of patients was assessed using the Cornell Medical Index (CMI). RESULTS Every item in the CMI questionnaire was negatively correlated with the OLT scores. Nine of 21 subjects (42.9%) diagnosed with pseudohalitosis and approximately 20% of subjects diagnosed with genuine halitosis were considered to be provisionally neurotic. Subjects with pseudohalitosis reported significantly higher physical scores, but not mental scores, than those with genuine halitosis. Subjects with physiologic halitosis showed significantly higher symptoms of depression than those with oral pathologic halitosis. CONCLUSION The psychologic condition of patients complaining of halitosis was associated with the actual degree of malodor and the clinical characteristics.

Differentiation-Inducing Factor-1 Alters Canonical Wnt Signaling and Suppresses Alkaline Phosphatase Expression in Osteoblast-Like Cell Lines

Because DIF‐1 has been shown to affect Wnt/β‐catenin signaling pathway, the effects of DIF‐1 on osteoblast‐like cell lines, SaOS‐2 and MC3T3‐E1, were examined. We found that DIF‐1 inhibited this pathway, resulting in the suppression of ALP promoter activity through the TCF/LEF binding site.

Discrimination of the oral microbiota associated with high hydrogen sulfide and methyl mercaptan production

Both hydrogen sulfide (H2S) and methyl mercaptan (CH3SH) are frequently detected in large amounts in malodorous mouth air. We investigated the bacterial composition of saliva of 30 subjects with severe oral malodor exhibiting extreme CH3SH/H2S ratios (high H2S but low CH3SH concentrations, n = 14; high CH3SH but low H2S concentrations, n = 16) and 13 subjects without malodor, using barcoded pyrosequencing analysis of the 16S rRNA gene. Phylogenetic community analysis with the UniFrac distance metric revealed a distinct bacterial community structure in each malodor group. The H2S group showed higher proportions of the genera Neisseria, Fusobacterium, Porphyromonas and SR1 than the other two groups, whereas the CH3SH group had higher proportions of the genera Prevotella, Veillonella, Atopobium, Megasphaera, and Selenomonas. Our results suggested that distinct bacterial populations in the oral microbiota are involved in production of high levels of H2S and CH3SH in the oral cavity.

Mixed Red-Complex Bacterial Infection in Periodontitis

The red complex, which includes Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia (formerly Bacteroides forsythus), are recognized as the most important pathogens in adult periodontal disease. These bacteria are usually found together in periodontal pockets, suggesting that they may cause destruction of the periodontal tissue in a cooperative manner. This article discusses the interspecies pathogenic interactions within the red complex.

Humoral Immune Responses to S-Layer-Like Proteins of Bacteroides forsythus

ABSTRACT Bacteroides forsythus is one of the important periodontopathic bacteria, and this microorganism is known to have an S-layer outside the outer membrane. The S-layer-like antigens were recently isolated from B. forsythus, and they were found to be 270- and 230-kDa proteins in the envelope fraction. In this study, these proteins were confirmed to be specific to B. forsythus by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and they were clearly recognized by sera from patients with adult and early-onset periodontitis in Western immmunoblot analysis. We compared the immunoglobulin G (IgG) responses against the purified S-layer-like antigen by enzyme-linked immunosorbent assay. IgG responses against this antigen were low in healthy control subjects, but they were significantly higher in subjects with adult and early-onset periodontitis. Together with the fact that the IgG responses against the crude extract of B. forsythus did not rise significantly in patients with periodontitis, S-layer-like proteins are considered to be specific antigens of B. forsythus and may play an important role in the progression of periodontitis.