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1.
J Am Heart Assoc ; 13(8): e033740, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38597139

ABSTRACT

BACKGROUND: Periodontitis has not been recognized as a modifiable risk factor for atrial fibrillation (AF). This prospective nonrandomized study investigated whether periodontal treatment improves the AF ablation outcome. METHODS AND RESULTS: We prospectively enrolled 288 AF patients scheduled to undergo initial radiofrequency catheter ablation. Each patient underwent periodontal inflamed surface area (PISA; a quantitative index of periodontal inflammation) measurement. All eligible patients were recommended to receive periodontal treatment within the blanking period, and 97 consented. During the mean follow-up period of 507±256 days, 70 (24%) AF recurrences were documented. Patients who exhibited AF recurrences had a higher PISA than those who did not (456.8±403.5 versus 277.7±259.0 mm2, P=0.001). These patients were categorized into high-PISA (>615 mm2) and low-PISA (<615 mm2) groups according to the receiver operating characteristic analysis for AF recurrence (area under the curve, 0.611; sensitivity, 39%; specificity, 89%). A high PISA, as well as female sex, AF duration, and left atrial volume, were the statistically significant predicter for AF recurrence (hazard ratio [HR], 2.308 [95% CI, 1.234-4.315]; P=0.009). In patients with a high PISA, those who underwent periodontal treatment showed significantly fewer AF recurrences (P=0.01, log-rank test). The adjusted HR of periodontal treatment for AF recurrence was 0.393 (95% CI, 0.215-0.719; P=0.002). CONCLUSIONS: Periodontitis may serve as a modifiable risk factor for AF. PISA is a hallmark of AF recurrence, and periodontal treatment improves the AF ablation outcome, especially for those with poor periodontal condition.


Subject(s)
Atrial Fibrillation , Catheter Ablation , Periodontitis , Humans , Female , Atrial Fibrillation/diagnosis , Atrial Fibrillation/surgery , Atrial Fibrillation/etiology , Prospective Studies , Heart Atria , Catheter Ablation/adverse effects , Recurrence , Treatment Outcome
2.
Oral Dis ; 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38656694

ABSTRACT

OBJECTIVE: To investigate the production of leucine-rich α-2-glycoprotein-1 (LRG1) in periodontitis patients and its effectiveness as a new diagnostic marker for periodontitis. SUBJECTS AND METHODS: In vitro experiments were conducted to analyze LRG1 mRNA expression in human gingival epithelial cells and fibroblasts via quantitative real-time PCR. In vivo experiments were conducted to analyze LRG1 localization in periodontitis patients. The correlation between the serum LRG1 levels and alveolar bone resorption in the mouse periodontitis model was also investigated. RESULTS: A positive correlation existed between the periodontal inflamed surface area and serum LRG1 levels (Spearman's rank correlation coefficient: 0.60). LRG1 mRNA expression in human gingival epithelial cells and fibroblasts was upregulated by Porphyromonas gingivalis stimulation or tumor necrosis factor-α stimulation. Interleukin-6 in human gingival epithelial cells and fibroblasts induced the production of LRG1 and transforming growth factor-ß. LRG1 levels in the periodontal tissue and serum in the periodontitis model were higher than those in control mice. LRG1 local administration resulted in alveolar bone resorption, whereas the administration of interleukin-6R antibody inhibited bone resorption. CONCLUSIONS: LRG1 levels in serum and periodontal tissue are upregulated in periodontitis and are implicated in periodontal tissue destruction through interleukin-6 production.

3.
Biomedicines ; 10(12)2022 Dec 01.
Article in English | MEDLINE | ID: mdl-36551860

ABSTRACT

Periodontal disease is predominantly caused by the pathogenic bacterium Porphyromonas gingivalis that produces inflammation-inducing factors in the host. Eucommia ulmoides is a plant native to China that has been reported to reduce blood pressure, promote weight loss, and exhibit anti-inflammatory effects. Geniposidic acid (GPA) is the major component of E. ulmoides. Herein, we investigated the effects of GPA on P. gingivalis-induced periodontitis by measuring the inflammatory responses in human gingival epithelial cells (HGECs) after P. gingivalis stimulation and GPA addition in a P. gingivalis-induced periodontitis mouse model. We found that GPA addition suppressed interleukin (IL)-6 mRNA induction (33.8% suppression), IL-6 production (69.2% suppression), toll-like receptor (TLR) 2 induction, and mitogen-activated protein kinase (MAPK) phosphorylation in HGECs stimulated by P. gingivalis. Inoculation of mice with GPA inhibited P. gingivalis-induced alveolar bone resorption (25.6% suppression) by suppressing IL-6 and TLR2 production in the serum and gingiva. GPA suppressed osteoclast differentiation of bone marrow cells induced by M-CSF and sRANKL in mice (56.7% suppression). GPA also suppressed the mRNA expression of OSCAR, NFATc1, c-Fos, cathepsin K, and DC-STAMP. In summary, GPA exerts an anti-inflammatory effect on periodontal tissue and may be effective in preventing periodontal disease.

4.
Int Immunopharmacol ; 68: 30-38, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30599445

ABSTRACT

Diabetic patients are at an increased risk of developing severe and progressive periodontitis. Periodontal disease also increases the severity of diabetes by enhancing insulin resistance. Therefore, the regulation of periodontal inflammation in diabetic patients may contribute to the control of both diseases. Glycyrrhizic acid exerts anti-inflammatory effects by inhibiting high mobility group box 1 (HMGB1). HMGB1, one of the ligands of the receptor for advanced glycation end products (RAGE), is a damage-associated molecular pattern and induces inflammatory cytokine production. In the present study, we examined the effects of glycyrrhizic acid on ligature- and Porphyromonas gulae infection-induced periodontitis as well as the involvement of the HMGB1-RAGE axis in diabetic model mice. The molars of diabetic model mice, established by feeding HFD32 to KK/TaJcl mice, were subjected to silk thread ligation and P. gulae was then intraorally applied in the presence or absence of glycyrrhizic acid given topically. The topical application of glycyrrhizic acid suppressed ligature/P. gulae-induced increases in interleukin (IL)-6 and tumor necrosis factor (TNF)-α at the mRNA level in the gingiva and at the protein level in serum. Furthermore, glycyrrhizic acid suppressed ligature/P. gulae-induced increases in serum amyloid A (SAA) in serum and fasting blood glucose levels. It also suppressed ligature/P. gulae-induced increases of HMGB1 and RAGE at the mRNA level in the gingiva and at the protein level in serum. A mouse anti-HMGB1-neutralizing antibody inhibited increases in serum glucose levels. In conclusion, topical treatments with glycyrrhizic acid may suppress periodontal and systemic inflammation and reduce blood glucose levels through the HMGB1-RAGE axis in diabetic mice.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Bacteroidaceae Infections/drug therapy , Diabetes Mellitus, Experimental/drug therapy , Glycyrrhizic Acid/therapeutic use , Hypoglycemic Agents/therapeutic use , Periodontitis/drug therapy , Porphyromonas , Animals , Anti-Inflammatory Agents/pharmacology , Bacteroidaceae Infections/immunology , Bacteroidaceae Infections/pathology , Blood Glucose/drug effects , Cells, Cultured , Cytokines/genetics , Cytokines/immunology , Diabetes Mellitus, Experimental/immunology , Diabetes Mellitus, Experimental/pathology , Fibroblasts/drug effects , Fibroblasts/immunology , Gingiva/immunology , Gingiva/pathology , Glycyrrhizic Acid/pharmacology , HMGB1 Protein/genetics , Hypoglycemic Agents/pharmacology , Male , Mice , Periodontitis/immunology , Periodontitis/pathology
5.
Jpn Dent Sci Rev ; 54(2): 66-75, 2018 May.
Article in English | MEDLINE | ID: mdl-29755617

ABSTRACT

Periodontal disease is a bacterial biofilm-associated inflammatory disease that has been implicated in many systemic diseases. A new preventive method for periodontal disease needs to be developed in order to promote the health of the elderly in a super-aged society. The gingival epithelium plays an important role as a mechanical barrier against bacterial invasion and a part of the innate immune response to infectious inflammation in periodontal tissue. The disorganization of cell-cell interactions and subsequent inflammation contribute to the initiation of periodontal disease. These make us consider that regulation of host defensive functions, epithelial barrier and neutrophil activity, may become novel preventive methods for periodontal inflammation. Based on this concept, we have found that several agents regulate the barrier function of gingival epithelial cells and suppress the accumulation of neutrophils in the gingival epithelium. We herein introduce the actions of irsogladine maleate, azithromycin, amphotericin B, and Houttuynia cordata (dokudami in Japanese), which is commonly used in traditional medicine, on the epithelial barrier and neutrophil migration in gingival epithelial cells in vivo and in vitro, in order to provide support for the clinical application of these agents to the prevention of periodontal inflammation.

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