Recombinant human fibroblast growth factor and autogenous bone for periodontal regeneration: Alone or in combination? A randomized clinical trial.

AIM: To compare the outcomes of therapy using recombinant human fibroblast growth factor (rhFGF)-2 combined with autologous bone grafting (ABG) therapy with those of rhFGF-2 alone and ABG alone in the treatment of periodontal intraosseous defects. METHODS: Periodontal intraosseous defects were randomized to receive rhFGF-2 therapy + ABG, rhFGF-2 therapy alone, or ABG alone. Periodontal examination and periapical radiography were performed preoperatively and at 3, 6, and 12 months postoperatively. RESULTS: At the 12 months follow-up, all three groups showed significant improvement in the clinical attachment level (CAL): 5.6 ± 1.6, 5.8 ± 1.7, and 5.2 ± 1.6 mm in the rhFGF-2 + ABG, rhFGF-2 alone, and ABG alone groups, respectively, with no significant inter-group differences (p < .05). rhFGF-2 therapy (alone or in combination) resulted in greater bone defect filling (BDF) (2.3 ± 1.2 mm and 2.6 ± 1.9 mm, respectively) than ABG therapy alone (1.2 ± 1.2 mm). Gingival recession was lesser in the ABG alone (1.2 ± 1.1 mm) and rhFGF-2 + ABG groups (1.4 ± 0.8 mm) than in the rhFGF-2 alone group (2.2 ± 1.2 mm). CONCLUSION: The results of this study showed that at 12 months postoperatively, all treatments resulted in statistically significant clinical improvements compared to the baseline. From these results, it can be concluded that rhFGF-2 promotes hard tissue regeneration in intraosseous defects.

Associations between Periodontal Status and Liver Function in the Japanese Population: A Cross-Sectional Study.

A relationship between periodontitis and liver function has been suggested. Indeed, patients with severe periodontal disease have been found to be more prone to liver dysfunction. The periodontal inflammatory surface area (PISA) has been shown to be a useful indicator of periodontal and systemic diseases. However, little information is available regarding whether the PISA is associated with liver function markers, such as gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). This study aimed to clarify relationship between liver function markers, AST, ALT, and GGT, and PISA level in a cross-sectional study. The subjects were recruited between 2018 and 2021 at the Medical and Dental Collaboration Center of Kanagawa Dental College Hospital. A periodontal clinical examination was performed, and the PISA was calculated. Peripheral blood samples were collected, and serum levels of liver function markers were measured. The levels of liver function markers were examined in different values of PISA. Participants with high PISA scores were more likely to have increased GGT levels while AST and ALT were not changed with PISA. Increased GGT was found in 10.8% and 29.4% (p = 0.0056), increased AST in 48.2% and 52.9% (p = 0.62), and increased ALT in 35.2% and 47.0% (p = 0.20) among <300 mm2 and ≧300 mm2 PISA groups, respectively. It was found that males with a PISA of 300 mm2 or higher had an elevated level of serum GGT. In conclusion, elevated GGT was found in the high PISA group, particularly in males, while AST and ALT did not differ by PISA.

Influence of Meal Sequence and Number of Teeth Present on Nutrient Intake Status: A Cross-Sectional Study.

Intake of fiber, as well as protein, and lipid preloading help to control postprandial glycemic elevation in people with type 2 diabetes and in healthy individuals. However, there are few studies on the awareness of meal sequence and nutrient intake status that consider oral conditions. This cross-sectional study aimed to determine the effects of meal sequences on nutrient intake status and whether these relationships were related to the number of teeth present. The subjects were recruited from the Medical and Dental Collaboration Center of Kanagawa Dental University Hospital between 2018 and 2021. Medical and dental examinations were performed, and a questionnaire was used to determine whether the diet consisted of vegetables, meat or fish, and carbohydrates in that order. Nutrient intake status was assessed using the brief-type self-administered diet history questionnaire. Data were collected from 238 participants. The group with awareness of meal sequence ingested increased nutrients such as n-3 fatty acids, total dietary fiber, calcium, and vitamin C. Saturated fatty acid intake increased in those with fewer teeth, while it was not significantly related to meal sequence. In conclusion, our results showed that meal sequence was associated with nutrient intake status. In addition, the intake of saturated fatty acids increased when many teeth were lost, regardless of meal sequence.

Development of a Japanese Version of the Formula for Calculating Periodontal Inflamed Surface Area: A Simulation Study.

The periodontal inflamed surface area (PISA) is a useful indicator of periodontal status. However, its formula was based on a meta-analysis involving five countries, and racial differences in tooth root morphology could have affected the calculations. This study aimed to develop a Japanese version of the PISA and compare it with the original version. The formulas reported by a previous Japanese study calculating the amount of remaining periodontal ligament from clinical attachment measurements were used to calculate the PISA. A simulation was performed to compare the Japanese version with the original version by inputting probing pocket depth (PPD) from 1 to10 mm and by using clinical data. The PISA values in the Japanese version were larger and smaller than those in the original version for PPDs of 1-5 mm and 6-10 mm, respectively. The PISA values for the clinical data from the Japanese version were significantly higher than those from the original version. Both versions of the PISA values correlated equally well with body mass index. The Japanese version of the PISA can be used to assess the amount of inflamed periodontal tissue resulting from periodontitis in Japanese populations, taking into account racial heterogeneity in root morphologies.

A cross-sectional study assessing the relationship between non-alcoholic fatty liver disease and periodontal disease.

The risk factors for non-alcoholic fatty liver disease (NAFLD) progression are not completely known. Porphyromonas gingivalis infection is a risk factor for systemic diseases. We investigated the association of P. gingivalis infection with the risk of non-alcoholic steatohepatitis progression. Here, hematological tests, periodontal examination, and saliva collection were performed for 164 patients with NAFLD. P. gingivalis was identified in saliva using polymerase chain reaction. Hepatic steatosis and stiffness were evaluated using vibration-controlled transient elastography (VCTE) and magnetic resonance imaging. In patients with NAFLD, P. gingivalis positivity (P. gingivalis ratio ≥ 0.01%) in saliva correlated with liver stiffness determined using magnetic resonance elastography (MRE; p < 0.0001). A P. gingivalis ratio of 0.01% corresponds to 100,000 cells/mL and indicates the proportion of P. gingivalis in the total number of bacteria in the oral cavity. Patients with NAFLD and advanced fibrosis on MRE showed significantly elevated endotoxin activity; those who had > 10 periodontal pockets with depths ≥ 4 mm had significantly increased hepatic stiffness on both VCTE and MRE.

Periodontal Treatment and Usual Care for Nonalcoholic Fatty Liver Disease: A Multicenter, Randomized Controlled Trial.

INTRODUCTION: Periodontal disease is associated with nonalcoholic fatty liver disease (NAFLD). We evaluated periodontal treatment efficacy in patients with NAFLD and periodontal disease. METHODS: This multicenter, 2-arm, randomized study recruited adult patients with NAFLD and periodontitis, alanine aminotransferase levels ≥40 U/L, and equivalent steatosis grade ≥1. Forty eligible patients (18 men and 22 women) were randomly assigned to 2 groups (scaling and root planning [SRP; n = 20] and tooth brushing [n = 20] groups) stratified by age and sex. The primary and secondary endpoints were changes in alanine aminotransferase levels and serum Porphyromonas gingivalis IgG antibody titers from baseline to 12 weeks, respectively. Efficacy analysis was performed using an intention-to-treat approach ( t test). This trial was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000022079). RESULTS: We observed a significantly higher decrease in absolute alanine aminotransferase levels and P. gingivalis IgG antibody titers in the SRP group than in the tooth brushing group (-12 vs 1 U/L; mean difference [δ], -12; 95% confidence interval [CI], -20 to -5; P = 0.002). The decrease in P. gingivalis IgG antibody titer was significantly higher in the SRP group than in the tooth brushing group (FDC381, -1.6 [2.5]; δ, -1.6; 95% CI, -2.7 to -0.4; P = 0.0092; SU63, -1.7 [2.0]; δ, -1.7; 95% CI, -2.7 to -0.7). No life-threatening events or treatment-related deaths occurred. DISCUSSION: Periodontal treatment induced significant short-term and mid-term reductions in liver enzyme levels and antibody titers. Further research is warranted to clearly define SRP efficacy and tolerability in patients with NAFLD and periodontitis.

Prospective Longitudinal Changes in the Periodontal Inflamed Surface Area Following Active Periodontal Treatment for Chronic Periodontitis.

Periodontal disease is a chronic inflammatory disease of the periodontal tissue. The periodontal inflamed surface area (PISA) is a proposed index for quantifying the inflammatory burden resulting from periodontitis lesions. This study aimed to investigate longitudinal changes in the periodontal status as evaluated by the PISA following the active periodontal treatment. To elucidate the prognostic factors of PISA, mixed-effect modeling was performed for clinical parameters, tooth-type, and levels of periodontal pathogens as independent variables. One-hundred-twenty-five patients with chronic periodontitis who completed the active periodontal treatment were followed-up for 24 months, with evaluations conducted at 6-month intervals. Five-times repeated measures of mean PISA values were 130+/-173, 161+/-276, 184+/-320, 175+/-417, and 209+/-469 mm2. Changes in clinical parameters and salivary and subgingival periodontal pathogens were analyzed by mixed-effect modeling. Plaque index, clinical attachment level, and salivary levels of Porphyromonas gingivalis were associated with changes in PISA at the patient- and tooth-level. Subgingival levels of P. gingivalis and Prevotella intermedia were associated with changes in PISA at the sample site. For most patients, changes in PISA were within 10% of baseline during the 24-month follow-up. However, an increase in the number of bleeding sites in a tooth with a deep periodontal pocket increased the PISA value exponentially.

Estimation of the Periodontal Inflamed Surface Area by Simple Oral Examination.

The periodontal inflamed surface area (PISA) is a useful index for clinical and epidemiological assessments, since it can represent the inflammation status of patients in one contentious variable. However, calculation of the PISA is difficult, requiring six point probing depth measurements with or without bleeding on probing on 28 teeth, followed by data input in a calculation program. More simple methods are essential for screening periodontal disease or in epidemiological studies. In this study, we tried to establish a convenient partial examination method to estimate PISA. Cross-sectional data of 254 subjects who completed active periodontal therapy were analyzed. Teeth that represent the PISA value were selected by an item response theory approach. The maxillary second molar, first premolar, and lateral incisor and the mandibular second molar and lateral incisor were selected. The sum of the PISAs of these teeth was significantly correlated with the patient's PISA (R2 = 0.938). More simply, the sum of the maximum values of probing pocket depth with bleeding for these teeth were also significantly correlated with the patient's PISA (R2 = 0.6457). The simple model presented in this study may be useful to estimate PISA.

Association of Periodontal Status, Number of Teeth, and Obesity: A Cross-Sectional Study in Japan.

Recent reports have shown an association between obesity and periodontitis, but the precise relationship between these conditions has yet to be clarified. The purpose of this study was to compare the status of periodontitis, tooth loss, and obesity. Participants comprised 235 patients at the Center for Medical and Dental Collaboration in Kanagawa Dental University Hospital between 2018 and 2020. Clinical examinations such as blood testing, body composition analysis, periodontal measurement, assessment of chewing ability, salivary testing, and oral malodor analysis were performed. Periodontal inflamed surface area (PISA) was significantly associated with the number of teeth and body mass index (BMI). The number of teeth was negatively associated with age, but positively with chewing ability. Chewing ability was associated negatively with age, and positively with high-sensitivity C-reactive protein (hsCRP). The level of methyl-mercaptan in breath and protein and leukocyte scores from salivary testing were positively associated with PISA. The rate of insufficient chewing ability was increased in subjects with hemoglobin (Hb)A1c ≥ 7%. The high PISA group showed increased hsCRP. BMI as an obesity marker was positively associated with PISA, indicating periodontal inflammation. Chewing ability was related to serum markers such as HbA1c and hsCRP.

Low education is associated with poor periodontal status in patients with type 2 diabetes mellitus: A cross-sectional study.

OBJECTIVES: Cardiovascular disease remains the most common cause of death in patients with type 2 diabetes mellitus. Because periodontitis is a risk factor of cardiovascular disease, identification of risk factors of periodontitis is valuable to control periodontitis effectively. The purpose of this study was to examine the association of education and household income with periodontal status in patients with type 2 diabetes mellitus. METHODS: Participants were 2,436 patients (59.8% male, aged 29-93 years) with type 2 diabetes mellitus from 27 medical clinics. Participants' medical records and information about education, household income, general health status, and health behaviors were collected. Periodontal status was assessed in a nearby dental office. Multiple linear regression analyses and ordered logistic regression analyses were conducted to examine the association of periodontal parameters with education and household income after adjusting for age, sex, general health status, and health behaviors. RESULTS: Multiple linear regression analysis showed that mean probing pocket depth was not significantly associated with education and household income. Ordered logistic regression analyses showed statistically significant odds ratios (ORs) of junior high school (reference: university) for the tertiles of the percentage of sites with bleeding on probing (OR: 1.42; 95% confidence interval [CI]: 1.11-1.81), percentage of mobile teeth (OR: 1.58; 95% CI: 1.24-2.03), and number of teeth present (OR: 0.51; 95% CI: 0.39-0.65), and statistically significant odds ratios of high school (reference: university) for the tertiles of the percentage of mobile teeth (OR: 1.27; 95% CI: 1.06-1.51) and number of teeth present (OR: 0.74; 95% CI: 0.62-0.88), but not household income. CONCLUSIONS: These results suggest that low education is one of the important predictors of poor periodontal status in patients with type 2 diabetes mellitus. It is important to provide targeted interventions including periodontal education in junior high school.

Optimal Examination Sites for Periodontal Disease Evaluation: Applying the Item Response Theory Graded Response Model.

Periodontal examination data have a complex structure. For epidemiological studies, mass screenings, and public health use, a simple index that represents the periodontal condition is necessary. Periodontal indices for partial examination of selected teeth have been developed. However, the selected teeth vary between indices, and a justification for the selection of examination teeth has not been presented. We applied a graded response model based on the item response theory to select optimal examination teeth and sites that represent periodontal conditions. Data were obtained from 254 patients who participated in a multicenter follow-up study. Baseline data were obtained from initial follow-up. Optimal examination sites were selected using item information calculated by graded response modeling. Twelve sites-maxillary 2nd premolar (palatal-medial), 1st premolar (palatal-distal), canine (palatal-medial), lateral incisor (palatal-central), central incisor (palatal-distal) and mandibular 1st premolar (lingual, medial)-were selected. Mean values for clinical attachment level, probing pocket depth, and bleeding on probing by full mouth examinations were used for objective variables. Measuring the clinical parameters of these sites can predict the results of full mouth examination. For calculating the periodontal index by partial oral examination, a justification for the selection of examination sites is essential. This study presents an evidence-based partial examination methodology and its modeling.

Effect of Periodontal Disease on Diabetic Retinopathy in Type 2 Diabetic Patients: A Cross-sectional Pilot Study.

Both periodontal disease and diabetes are common chronic inflammatory diseases. One of the major problems with type 2 diabetes is that unregulated blood glucose levels damage the vascular endothelium and cause complications. A bidirectional relationship between periodontal disease and diabetic complications has been reported previously. However, whether periodontal disease affects the presence of diabetic complications has not been clarified. Therefore, we examined the effect of the periodontal disease status on diabetic complications in patients with type 2 diabetes. Periodontal doctors examined the periodontal disease status of 104 type 2 diabetic patients who visited a private diabetes medical clinic once a month between 2016 and 2018. The subject's diabetic status was obtained from their medical records. Bayesian network analysis showed that bleeding on probing directly influenced the presence of diabetic retinopathy in type 2 diabetes patients. In addition, bleeding on probing was higher in the diabetic retinopathy group (n = 36) than in the group without diabetic retinopathy (n = 68, p = 0.006, Welch's t-test). Bleeding on probing represents gingival inflammation, which might affect the presence of diabetic retinopathy in type 2 diabetes patients who regularly visit diabetic clinics.

Association between periodontitis and vascular endothelial function using noninvasive medical device-A pilot study.

The present study aimed to assess the relationship between periodontal condition and endothelial function using a noninvasive device. Many recent studies have reported associations between periodontitis and cardiovascular diseases. Endothelial dysfunction is the first step of atherosclerosis, but information on the association between periodontal disease and endothelial dysfunction remains limited. Thirty-three subjects were recruited from among patients at a private medical clinic. We examined vascular endothelial function using a noninvasive medical device and periodontal measurements including probing pocket depth, attachment level, tooth mobility, and oral cleaning condition. Subjects were divided into two groups according to endothelial function score. Tooth mobility and number of lost teeth were increased in the group with endothelial dysfunction. A greater frequency of elderly subjects and altered hemoglobin A1c levels were seen in the endothelial dysfunction group. On multiple logistic regression analysis, increased tooth mobility was independently associated with endothelial dysfunction. Increased tooth mobility, a major periodontal parameter, appears related to endothelial dysfunction.

Inhibitory effect of omega-3 fatty acids on alveolar bone resorption and osteoclast differentiation.

In this study, a Porphyromonas gingivalis (P.g.)-infected mouse periodontitis model was used to investigate the effect of omega-3 fatty acid intake on differentiation and maturation of cultured osteoclast. Four-week-old C57BL/6JJcl mice were divided into four groups according to the diets they were fed from the beginning of the experiment (i.e., food containing omega-3 or omega-6 fatty acids) and whether they were orally administered P.g. Thirty-three days after beginning the experiment, bone marrow cells were sampled from the femoral bone of mice from each group and differentiated into osteoclasts; the effects of the ingestion of different fatty acids were subsequently investigated. There was no statistical interaction between the different fatty acids and P.g. infection on the number of osteoclasts (P = 0.6). However, the fatty acid type affected the number of osteoclasts in mice (P = 0.0013), with the omega-3 groups demonstrating lower osteoclast numbers than the omega-6 groups. Furthermore, the addition of resolvin E1 (RvE1), which is an omega-3 fatty acid-derived lipid mediator, suppressed the differentiation of mouse cultured osteoclasts (P < 0.0001). Therefore, the ingestion of omega-3 fatty acids may suppress osteoclast differentiation while inhibiting bone resorption and tissue destruction due to periodontitis.

Efficacy and safety of PERIOdontal treatment versus usual care for Nonalcoholic liver disease: protocol of the PERION multicenter, two-arm, open-label, randomized trial.

BACKGROUND: We report the first protocol for a multicenter, randomized comparison study to compare the efficacies of periodontal scaling and root-planing treatment against that of tooth-brushing treatment for nonalcoholic fatty liver disease (NAFLD) (PERION: PERIOdontal treatment for NAFLD). Nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD, which can progress to cirrhosis and hepatocellular carcinoma. Increased endotoxemia is associated with the progression of NAFLD. Periodontal bacteria possess endotoxins; Porphyromonas gingivalis is well-known as a major pathogenic bacterium in periodontitis, and serum antibody levels for P. gingivalis are high in patients with periodontitis. Several reports have indicated that P. gingivalis is related to NAFLD. This study aims to investigate the effect of periodontal treatment for liver damage, P. gingivalis infection, and endotoxemia on patients with NAFLD. METHODS: We will include adult patients (20-85 years old) with NAFLD, alanine aminotransferase (ALT) ≥ 40 IU/L, and equivalent steatosis grade ≥ 1 (target sample size, n = 40 patients; planned number of patients with outcome data, n = 32). Participants will be randomly assigned to one of two groups: a scaling and root-planing group or tooth-brushing as the usual group. The primary outcome will be the change in ALT levels from baseline to 12 weeks; the key secondary outcome will be the change in the serum immunoglobulin G (IgG) antibody titer for P. gingivalis at 12 weeks. DISCUSSION: This study should determine whether periodontal treatment decreases liver damage, P. gingivalis infection, and endotoxemia in patients with NAFLD. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN) Clinical Trials Registry, ID: UMIN000022079.

Association of urinary albumin excretion with periodontal parameters in patients with type 2 diabetes mellitus: a cross-sectional study.

BACKGROUND: Our previous pilot study using patients with type 2 diabetes mellitus in one medical clinic showed an association of urinary albumin excretion, a marker of generalized vascular dysfunction and kidney damage, with periodontitis. The purpose of this study was to confirm the association by increasing the number of patients and medical clinics. METHODS: Participants were 2302 patients (59.9% males, aged 29-93 years) with type 2 diabetes mellitus from 25 medical clinics. Their medical records and information about socioeconomic status and health behavior were collected. Periodontal status was assessed in a nearby dental office. Multiple linear regression analyses were conducted to examine the association of log-transformed urinary albumin-to-creatinine ratio with periodontal parameters after adjusting for sociodemographic status, general health conditions, and health behaviors. The analyses were performed in all subjects and subjects with normoalbuminuria only. RESULTS: Multiple linear regression analysis showed that mean probing pocket depth (beta: 0.062), percentage of sites with probing pocket depth of 4 mm or deeper (beta: 0.068), percentage of mobile teeth (beta: 0.055), and severity of periodontitis (beta: 0.049) were significantly (p < 0.05) correlated with log-transformed urinary albumin-to-creatinine ratio after adjusting for possible confounders in all subjects. However, no significant associations between urinary albumin-to-creatinine ratio and periodontal parameters were observed in subjects with normoalbuminuria only. CONCLUSIONS: These results suggest that periodontitis is associated with urinary albumin excretion in patients with type 2 diabetes mellitus. Collaboration between medical and dental healthcare providers is needed for treatment of diabetes and periodontitis.

Albuminuria, C-reactive protein, and socioeconomic factors are associated with periodontal status in subjects with type 2 diabetes.

Diabetes and periodontitis may increase risk of cardiovascular disease. Whether albuminuria, C-reactive protein (CRP), and socioeconomic factors, known as cardiovascular risks in subjects with poorly controlled diabetes, are independently associated with periodontal status in well-controlled diabetes remains to be elucidated. In 503 subjects with type 2 diabetes, the cross-sectional associations of clinical and socioeconomic factors with periodontal parameters were investigated. Periodontal parameters on all teeth included the probing pocket depth at 6 sites per tooth, bleeding on probing, the plaque score, tooth mobility, and the number of teeth. The subjects had a mean HbA1c value of 6.85% and a median CRP value of 0.06 mg/dL, and 27.9% of the subjects had albuminuria. Albuminuria and CRP values had significant associations with several periodontal parameters, whereas other variables including HbA1c did not. Subjects with albuminuria had significantly higher HbA1c, CRP, and % sites of pocket depth ≥ 4 mm than subjects with normoalbuminuria; additionally, those with high CRP (≥ median) had significantly higher body mass index, HbA1c, % sites of pocket depth ≥ 4 mm, and plaque score than those with low CRP. In multiple linear regression analysis, albuminuria, CRP, education, smoking, and dental attendance exhibited significant associations with periodontal parameters, independent of the effect of age, sex, body mass index, and diabetes therapy. Albuminuria, CRP, education, smoking, and dental attendance were independently associated with periodontal parameters even in subjects with a mean of HbA1c of 6.85%, implying the importance of these factors for the prevention of cardiovascular disease.

Increased Heart Failure Prevalence in Patients with a High Antibody Level Against Periodontal Pathogen.

The aim of this study was to assess whether a specific cardiovascular disease was related to an increased antibody level against a periodontal pathogen.A strong association between cardiovascular disease and periodontitis was shown, however, the causal relationship was not proven. Increased inflammatory reaction of patients with periodontitis was a possible factor, which connected periodontal infection and vascular diseases.We assessed medical history, blood data, and periodontal conditions in patients with cardiovascular diseases. Serum IgG antibody titers against major periodontal pathogens and existence of salivary periodontal bacteria were analyzed.In total, 348 subjects were enrolled in this study. The patients who exhibited 10,000 counts/mL or more of salivary Porphyromonas gingivalis were divided into two groups according to the antibody level of the pathogen. Patients with a high antibody level against Porphyromonas gingivalis exhibited a high rate of heart failure compared to the low antibody group. Mean probing pocket depth and clinical attachment level significantly increased in the high antibody group. We found that the high anti-Porphyromonas gingivalis antibody group also experienced enhanced antibody levels against other periodontal bacteria.An increased heart failure prevalence was found in patients with a high antibody level against a major periodontal pathogen, Porphyromonas gingivalis.

Biological responses following one-stage full-mouth scaling and root planing with and without azithromycin: Multicenter randomized trial.

BACKGROUND AND OBJECTIVE: Full-mouth scaling and root planing (FM-SRP) increases the systemic levels of inflammatory mediators via early inflammation but may be inhibited using an antimicrobial agent. This prospective intervention study evaluates the biological response and clinical effects of FM-SRP with and without systemically administered azithromycin (AZM). MATERIALS AND METHODS: A multicenter parallel randomized controlled and open-label trial. A central randomization center used computer-generated tables to allocate treatments. Sixty-three patients with moderate to severe generalized periodontitis (New American Academy of Periodontology Classification: Stage3 or 4, Grade B) were randomly assigned to receive FM-SRP with AZM (test group, n = 32) or FM-SRP without AZM (control group, n = 31). Clinical parameters and body temperature were measured, and subgingival plaque, peripheral blood, and gingival crevicular fluid were collected before and after treatment. Periodontopathic bacteria and IgG titers were measured by gingival crevicular fluid and peripheral blood. High-sensitivity assays were used to analyze systemic and local inflammatory markers, such as endotoxin, high-sensitive CRP (hs-CRP), and six inflammatory cytokines. Follow-up 6 weeks. RESULTS: The total number of bacteria and the number of Porphyromonas gingivalis and Prevotella intermedia were significantly lower in the test group after FM-SRP. IgG titers for P gingivalis significantly decreased after FM-SRP with AZM, and the body temperature increased significantly after FM-SRP without AZM. In the control group, serum hs-CRP, IFN-γ, IL-12p70, and IL-6 were significantly increased one day after treatment, but subsequently decreased below the original numerical value. In the test group, only hs-CRP showed a significant increase. CONCLUSIONS: FM-SRP resulted in similar improvements in clinical parameters with and without the use of AZM. Inflammatory mediators showed no difference between the two groups after FM-SRP treatment. The use of AZM was effective in preventing the elevation of body temperature after FM-SRP.

Inhibitory effects of azithromycin on the adherence ability of Porphyromonas gingivalis.

BACKGROUND: Porphyromonas gingivalis is a major pathogen and has a high detection rate in periodontal disease. Fimbriae and hemagglutinin are expressed by P. gingivalis, and these play an important role in the adherence of the bacteria to periodontal tissue and biofilm formation. The aim of this study was to investigate the effects of sub-minimal inhibitory concentrations (sub-MICs) of azithromycin on the adherence of P. gingivalis, focusing on the inhibition of fimbriae expression and hemagglutinin activity. METHODS: P. gingivalis ATCC 33277 were incubated anaerobically with sub-MICs of azithromycin at 37°C by gentle shaking for 18 hours. The bacterial cells were harvested, washed twice with phosphate-buffered saline (PBS), and the proteins analyzed by 12% sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and western blotting. Adherence assay and hemagglutinin activity tests were done with the same culture. RESULTS: The results of SDS-PAGE indicated that the sub-MICs of azithromycin inhibited 41-kDa fimbrial protein expression and hemagglutinin activities. The disappearance of 41-kDa fimbrial protein expression and long fimbriae in 0.4 µg/mL, 0.2 µg/mL, and 0.1 µg/mL of azithromycin was confirmed by western blotting and transmission electron microscopy. The adherence of P. gingivalis to human gingival epithelial cells was reduced by sub-MICs of azithromycin compared with the adherence levels without antibiotic. CONCLUSIONS: These results suggest that sub-MICs of azithromycin may reduce the adherence of P. gingivalis to host cells, by inhibiting production of fimbriae and hemagglutinin activities. Therefore, azithromycin can be used as a biofilm treatment of periodontal disease caused by P. gingivalis.