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.

Effect of ingesting yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 on influenza virus-bound salivary IgA in elderly residents of nursing homes: a randomized controlled trial.

Objective: The purpose of this study was to clarify the influence of consuming yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 (1073R-1-yogurt) on influenza virus-bound salivary immunoglobulin A (IgA) levels, in the elderly residents of nursing homes. Methods: A double-blind, parallel-group, randomized controlled trial was conducted with 96 elderly volunteers residing in 2 nursing homes. During the trial, participants consumed 100 g of 1073R-1-yogurt every morning for 12 weeks, whereas the control participants consumed yogurt fermented with a different Lactobacillus strain (control yogurt). Saliva was collected before the trial and after 4, 8 and 12 weeks of yogurt ingestion. Results: Our data indicated that consumption of 1073R-1-yogurt affected influenza A virus subtype H3N2-bound IgA levels in saliva (p = .001). In addition, saliva flow rate and total IgA levels increased in response to the yogurt intake period in both the 1073R-1 and control yogurt groups (p = .04). Conclusions: Our study suggests that continuous daily ingestion of 1073R-1-yogurt may help prevent infection with influenza A virus subtype H3N2 in elderly subjects with weakened immunity, by increasing the production of influenza A virus subtype of H3N2-bound salivary IgA.

Human ß-defensin-2 and interleukin-1ß expression in response to Porphyromonas gingivalis challenge in mice transplanted with periodontitic human gingiva.

Inter-individual variability in the host response contributes significantly to expression of periodontal disease. Thus, research into the human host response is considered important in the analysis of periodontal disease. Human ß-defensin-2 (hBD-2) is typically produced by epithelial tissues after stimulation with microorganisms and inflammatory mediators, and it contributes to the initial defense in the innate immune response. However, hBD-2 expression in response to infection has not been investigated in human gingival tissue with periodontitis. We examined the response to Porphyromonas gingivalis in an established in vivo model of human gingival grafts with various degrees of periodontitis. We also investigated the expression profile of interleukin-1ß (IL-1ß). Gingival tissues were collected from 40 patients with chronic periodontitis (21 with slight-to-moderate disease, 19 with severe disease) during tooth extraction or periodontal surgery. These tissues were transplanted subcutaneously into nu/nu mice. We used real-time PCR to compare the expression of hBD-2 and IL-1ß. In slight-to-moderate chronic periodontitis, hBD-2 expression was significantly higher in the stimulated group than in the non-stimulated group (p < 0.05), but there was no significant increase in the group with severe chronic periodontitis. IL-1ß expression did not differ between groups. Increased expression of hBD-2 and IL-1ß was associated with slight-to-moderate periodontitis (p < 0.05), and there was a significant relationship between decreased hBD-2 and IL-1ß expression and severe periodontitis (p < 0.05). The initial expression profile of hBD-2 in P. gingivalis infection differs according to the severity of periodontitis. In addition, changes in hBD-2 and IL-1ß expression may be important in the progression of periodontitis.

Intake of indigestible carbohydrates influences IgA response and polymeric Ig receptor expression in the rat submandibular gland.

Secretory IgA in the saliva is essential for protection from mucosally transmitted pathogens and maintaining homeostasis at mucosal surfaces of the oral cavity. Expression of submandibular gland polymeric Ig receptor (pIgR) is essential for IgA secretion. In the present study, we investigated the influence of indigestible carbohydrates on IgA production in the salivary gland and saliva. Five-week-old rats were fed a fibre-free diet (control), or a diet with 5 % (w/w) fructo-oligosaccharide (FOS) or a combination of 2·5 % (w/w) polydextrose (PDX) and 2·5 % (w/w) lactitol for 21-d. IgA concentrations in the caecal digesta, submandibular gland tissue, and saliva in the FOS and PDX+lactitol diet groups were significantly higher than those in the control group (P< 0·05). The increase in IgA in the submandibular gland tissue was confirmed using immunohistochemical analysis. However, the IgA concentrations of serum did not differ between the FOS or PDX+lactitol groups and the control group (P= 0·5). In the FOS and PDX+lactitol groups, the pIgR mRNA (pIgR/ß-actin) expression level in the submandibular gland tissue was significantly higher than that in the control group (P< 0·05). The present study suggests that indigestible carbohydrates play an important role in the increase in IgA concentrations in the submandibular gland tissue, saliva, and caecal digesta.

Associations between brain-derived neurotrophic factor and estradiol in women's saliva.

OBJECTIVE: The aim of this study was to assess the relationship between brain-derived neurotrophic factor (BDNF) and sex hormones (estradiol [E2] and progesterone), using saliva samples obtained from healthy women. METHODS: Forty female dental hygienist students were divided into groups according to being in the follicular phase or luteal phase. Saliva BDNF, E2, and progesterone levels were measured using a sandwich ELISA system. The correlation between these factors was analyzed using Spearman's index, and fluctuations of these levels in the whole menstrual cycle were investigated classifying the subjects by every 4 days according to the phase of their menstrual cycle. RESULTS: Saliva BDNF variations strongly correlated with saliva E2 levels in the follicular phase (r = 0.721, p = 0.000) and luteal phase (r = 0.770, p = 0.000). The correlation coefficient showing the relationship between progesterone and BDNF levels in the luteal phase (r = 0.371, p = 0.157) was lower than that in the follicular phase (r = 0.631, p = 0.001). Moreover, the fluctuation of BDNF levels in the menstrual cycle followed a similar pattern to that of E2. CONCLUSIONS: We found that saliva BDNF and E2 levels were closely related in healthy young women. In particular, for first time, that correlation was investigated throughout the menstrual cycle. Monitoring of saliva BDNF may yield insight into women's reproductive and mental health.

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.

Periodontal Tissue Healing After Autologous Tooth Transplantation: A Retrospective Analysis of Case Series.

PURPOSE: Tooth transplantation is a treatment that uses non-functional teeth to compensate for defects caused by tooth extractions. Surgical procedures have yielded high success rates in autologous tooth transplantation using a tooth with a complete root. This study aimed to evaluate periodontal tissue healing after transplantation of 14 molar teeth. MATERIALS AND METHODS: Fourteen individuals aged 28-53 years who underwent autologous transplantation of third molars with completely developed roots between December 2010 and March 2017 were included in the study. The donor tooth was carefully extracted, placed into the prepared transplant site, and stabilised with an orthodontic wire and 4-0 silk sutures for a few weeks. Endodontic treatment was performed after 3-4 weeks. To evaluate the periodontal tissue healing, clinical measurements of the probing pocket depth (PPD), clinical attachment level (CAL), and keratinised gingival width (KGW) were performed, along with radiographic examinations of bone defect fill (BDF) at baseline and at 6 and 12 months after surgery. Statistical analysis was performed using the Mann-Whitney U test. RESULTS: The changes in PPD and CAL at baseline, 6, and 12 months were statistically significant (P <0.05). KGW did not show a statistically significant decrease. The postoperative-BDF amount at 6 and 12 months was 2.2 ± 1.4 and 4.2 ± 1.4 mm, respectively. CONCLUSION: Periodontal tissue healing may occur in tooth autotransplantation even in the presence of complete root development in the donor tooth.

Effect of High Fat and Fructo-Oligosaccharide Consumption on Immunoglobulin A in Saliva and Salivary Glands in Rats.

Consumption of indigestible dietary fiber increases immunoglobulin A (IgA) levels in saliva. The purpose of this study is to clarify the synergistic effect of the intake of a high amount of fats and indigestible dietary fiber on IgA levels in saliva and submandibular glands (SMG). Seven-week-old Wistar rats were fed a low-fat (60 g/kg) fiberless diet, low-fat fructo-oligosaccharide (FOS, 30 g/kg) diet, high-fat (220 g/kg) fiberless diet, or high-fat FOS diet for 70 days. The IgA flow rate of saliva (IgA FR-saliva) was higher in the low-fat FOS group than in the other groups (p < 0.05). Furthermore, the concentration of tyrosine hydroxylase (a marker of sympathetic nerve activation) in the SMG was higher in the low-fat FOS group (p < 0.05) and positively correlated with the IgA FR-saliva (rs = 0.68. p < 0.0001. n = 32) in comparison to that in the other groups. These findings suggest that during low-fat FOS intake, salivary IgA levels may increase through sympathetic nerve activation.

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.

Effect of social isolation stress on saliva BDNF in rat.

Salivary glands produce various compounds, including brain-derived neurotrophic factor (BDNF), which serve as biomarkers of stress-related disorders. Social isolation-induced stress models a form of chronic mild stress that induces neurodegenerative changes in the brain and behavioral alterations. This study employed a rat model to determine whether social isolation stress affects BDNF levels in saliva. Male Sprague-Dawley rats were randomly allocated to social isolation stress (1 animal/cage) or control (3-4 animals/cage) groups and reared for 8 weeks. The concentration of BDNF was quantified in specific brain regions, blood, and saliva using enzyme-linked immunosorbent assay (ELISA). The levels of expression of Bdnf and tyrosine kinase B (TrkB) mRNA were quantified using reverse transcriptase-polymerase chain reaction. Behavioral alterations were analyzed using the open-field and elevated plus maze assays. The BDNF concentration was lower in the hippocampus, prefrontal cortex, blood, and saliva of the stress group than in those of the controls. Trkb expression in the hippocampus and prefrontal cortex was decreased by social isolation stress. Moreover, the social isolation stress group showed behavioral deficits in both tests. In conclusion, these findings indicate that social isolation stress may reduce the expression of BDNF protein in blood and saliva, thus providing a potentially valuable biomarker for diagnosis of stress-related disorders.

Continuous combined intake of polydextrose and lactitol stimulates cecal fermentation and salivary IgA secretion in rats.

Immunoglobulin A (IgA), which plays an important role in infection defense, is upregulated in the large intestine and oral cavity through dietary fiber intake. However, the mechanism underlying salivary IgA increase through dietary fiber intake remains unknown. This study investigated time-dependent effects of non-absorbable polydextrose (PDX) and lactitol intake on salivary IgA secretion and cecal fermentation. Five-week-old rats were fed a fiber-free diet with or without 25 g/kg PDX and 25 g/kg lactitol for 1, 4, and 8 weeks. Compared to control, those who ingested PDX and lactitol had higher salivary IgA flow rates per weight of submandibular gland tissue at 4 and 8 weeks (P < 0.05), greater cecal weight and digesta at 1, 4, and 8 weeks (P < 0.05), and lower concentrations of short chain fatty acids (SCFAs) in cecal digesta (P = 0.0003). These findings suggest that the consumption of PDX and lactitol may upregulate salivary IgA secretion possibly by stimulating absorption of SCFAs produced by cecal fermentation. Thus, continuous ingestion of PDX and lactitol for up to 4 weeks could increase salivary IgA and promote immune defense against pathogen invasion through the oral route.

Grinding patterns in migraine patients with sleep bruxism: a case-controlled study.

OBJECTIVES: Details on grinding patterns and types of contact during sleep bruxism in association with migraine headache have not yet been elucidated. This study compared the characteristics of sleep bruxism between patients with migraine and controls. METHODS: The study included 80 female patients who had been diagnosed with migraine and 52 women with no history of migraine. Grinding patterns were measured using the BruxChecker® (Scheu Dental, Iserlohn, Germany). RESULTS: There was a significant difference between the two groups in the distribution of grinding patterns at the laterotrusive side (p < 0.001). When the anterior teeth and premolar and molar regions in the two groups were compared, the proportion of the grinding area at all sites was significantly larger in the migraine group than in the control group (p < 0.001). DISCUSSION: The BruxChecker® showed that there was substantial grinding over a large area among migraine patients, particularly in the molar region.

Features of occlusal state in female Japanese patients with migraine: a case-controlled study.

OBJECTIVES: The prevalence rate of migraines is 8.4%; it is mostly diagnosed in women at 20s to 40s, and is known to cause major physical and mental disruption to daily life. This study was conducted on women aged between their 20s and 40s, in order to investigate the possible differences in the features of the occlusal state between a migraine and a non-migraine (control) group. METHODS: Age-matched female patients with migraine (n = 60) diagnosed by headache specialists and healthy controls (n = 57) were enrolled. Dental casts were used to evaluate some features. RESULTS: The maxillary and mandibular dentition casts from the migraine group showed significantly characteristic findings in their Angle's classification, overjet, and deviation in the anterior tooth midline, compared to the control group. DISCUSSION: The results relating occlusal state to both tension-related headaches and migraines, which have different pathogeneses, suggest the possibility of dental intervention to improve the symptoms of primary headaches.

The Salivary IgA Flow Rate Is Increased by High Concentrations of Short-Chain Fatty Acids in the Cecum of Rats Ingesting Fructooligosaccharides.

Salivary immunoglobulin A (IgA) serves as a major effector in mucosal immunity by preventing submucosal invasion of pathogens. However, the mechanism by which consumption of fermentable fibers increases IgA in saliva was not fully elucidated. This study investigated the effects of fructooligosaccharides (FOS) intake and time after feeding on IgA levels in the saliva and cecal digesta and on the concentration of short-chain fatty acids (SCFA) in the cecum in rats. Five-week-old rats were fed a fiber-free diet or a diet with 50 g/kg FOS for zero, one, four, and eight weeks. Ingestion of FOS at one and eight weeks led to a higher IgA flow rate of saliva per weight of submandibular gland tissue (p < 0.05), which positively correlated with the concentration of SCFA in the cecal digesta (rs = 0.86, p = 0.0006, n = 12), but showed no correlation with the concentration of IgA in the cecal digesta (rs = 0.15, p = 0.3, n = 48). These results suggested that ingestion of FOS increased salivary IgA secretion through high levels of SCFA in the large intestine, which was produced by fermentation of FOS. Thus, continuously ingesting FOS for more than one week could increase secretion of salivary IgA.

Induction of ß-Defensin Expression by Porphyromonas gingivalis-Infected Human Gingival Graft Transplanted in nu/nu Mouse Subdermis.

It is important to understand the onset of periodontal disease in terms of bacterial infection and host factors. Host-bacteria interactions can be elicited in human cultured cells and animal models, but these models provide only limited biological information about human host reactions against bacterial attacks. Development of an in vivo model using human gingival tissue is needed. We established an in vivo model using nu/nu mice and evaluated host defense following bacterial infection in human gingiva. Human gingival samples were collected from periodontitis patients and transplanted in nu/nu mouse subdermis. After 2 weeks, human characteristics were confirmed by positive immunohistochemical reactions for human-specific markers. We used this model to investigate human ß-defensin-2 (hBD-2), an antimicrobial peptide that contributes to initial defense against bacterial invasion. Using real-time polymerase chain reaction, in situ hybridization, and immunohistochemistry, we investigated whether hBD-2 expression was induced in human gingiva as a response to Porphyromonas gingivalis as a periodontal pathogen. Two hours after infection with bacteria, we detected increased expression of hBD-2 mRNA, which was localized in the epithelium of human gingiva. Using our in vivo model, we concluded that increased hBD-2 may play an important role in early defense from bacterial infection in human gingival epithelium.