Faculty Profiles - MARUYAMA Takayuki

Papers - MARUYAMA Takayuki

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Effects of Trehalose on Halitosis: A Randomized Cross-Over Clinical Trial. International journal

Hisataka Miyai, Takaaki Tomofuji, Hirofumi Mizuno, Manabu Morita, Momoko Nakahara, Kota Kataoka, Ichiro Sumita, Yurika Uchida, Naoki Toyama, Aya Yokoi, Reiko Yamanaka-Kohno, Noriko Takeuchi, Takayuki Maruyama, Daisuke Ekuni

Healthcare (Basel, Switzerland) 13 ( 6 ) 2025.3

Language：English Publishing type：Research paper (scientific journal)

Background/Objectives: Halitosis is a condition characterized by an unpleasant malodor. Intra-oral halitosis is caused by volatile sulfur compounds (VSCs) and can be associated with oral dryness. Trehalose is one of the materials used to relieve oral dryness. The aim of the present study was to investigate the effect of trehalose on halitosis. Methods: This prospective, double-blinded, placebo-controlled, cross-over study enrolled volunteers from Okayama University Hospital. The participants were randomly divided into two groups, with one group receiving trehalose (a 10% trehalose solution) and the other receiving a placebo (distilled water) in a 1:1 allocation. The primary study outcome was the subjective organoleptic test. The secondary outcomes were the concentrations of the VSCs, which were measured using a portable gas chromatography device, and the oral moisture status, which was measured using an oral moisture meter. The planned sample size was 10 participants based on the previous study. Results: The final intention-to-treat analysis was performed using the data from 9 participants. After applying 10% trehalose as an oral spray, the organoleptic score decreased in a time-dependent manner. However, no significant differences were seen between the trehalose and placebo groups. In terms of secondary outcomes, the oral moisture levels increased immediately after the trehalose spray application, and significant differences in the amount of change from the baseline were seen between the trehalose and placebo groups (p = 0.047). No significant differences were seen in any of the other variables (p > 0.05). Conclusions: We could not identify any positive effects on halitosis from a one-time 10% trehalose application as an oral spray in this prospective, double-blinded, placebo-controlled, cross-over study. However, the trehalose application immediately improved the oral moisture levels and was useful for treating oral dryness.

DOI： 10.3390/healthcare13060619

Efficacy of Oral Intake of Hydrogen-Rich Jelly Intake on Gingival Inflammation: A Double-Blind, Placebo-Controlled and Exploratory Randomized Clinical Trial. International journal

Takayuki Maruyama, Eiji Takayama, Shinichi Tokuno, Manabu Morita, Daisuke Ekuni

Healthcare (Basel, Switzerland) 13 ( 5 ) 2025.3

Language：English Publishing type：Research paper (scientific journal)

Background/Objectives: Initiation and progression of periodontal disease include oxidative stress. Systemic application of antioxidants may provide clinical benefits against periodontal disease including gingivitis. Recently, a jelly containing a high concentration of hydrogen (40 ppm) was developed. We hypothesized that oral intake of this hydrogen-rich jelly may be safe and effective on gingivitis. This clinical trial was designed to investigate the safety and efficacy of oral intake of hydrogen-rich jelly against gingival inflammation. Methods: Participants with gingivitis were instructed to orally ingest 30 g of hydrogen-rich jelly (experimental group) or placebo jelly (control group) three times a day for 14 consecutive days. The primary outcome of this trial was the percentage of bleeding on probing (BOP) sites. Secondary outcomes were oral parameters, serum reactive oxygen metabolites, antioxidant capacity, oxidative index, concentrations of cytokine (interleukin [IL]-1β, IL-6, IL-10, IL-17, and tumor necrosis factor-alpha) in gingival crevicular fluid, and adverse events. For all parameters, Mann-Whitney U test was used for comparison between experimental and control groups. Analysis of covariance, controlling for baseline periodontal inflamed surface area, was performed to evaluate the association between the effect of the hydrogen-rich jelly and gingival inflammation. Results: In the experiment and control groups, the percentage of sites with BOP and PISA significantly decreased at the end of the experiment compared to the baseline. However, no significant differences were found between groups (p > 0.05). Conclusions: Administration of hydrogen-rich jelly for 14 days decreased gingival inflammation. However, no significant differences were identified compared to the control group.

DOI： 10.3390/healthcare13050577

Efficacy of Oral Intake of Hydrogen-Rich Jelly Intake on Gingival Inflammation: A Double-Blind, Placebo-Controlled and Exploratory Randomized Clinical Trial

Takayuki Maruyama, Eiji Takayama, Shinichi Tokuno, Manabu Morita, Daisuke Ekuni

Healthcare (Switzerland) 13 ( 5 ) 2025.3

Publishing type：Research paper (scientific journal)

Background/Objectives: Initiation and progression of periodontal disease include oxidative stress. Systemic application of antioxidants may provide clinical benefits against periodontal disease including gingivitis. Recently, a jelly containing a high concentration of hydrogen (40 ppm) was developed. We hypothesized that oral intake of this hydrogen-rich jelly may be safe and effective on gingivitis. This clinical trial was designed to investigate the safety and efficacy of oral intake of hydrogen-rich jelly against gingival inflammation. Methods: Participants with gingivitis were instructed to orally ingest 30 g of hydrogen-rich jelly (experimental group) or placebo jelly (control group) three times a day for 14 consecutive days. The primary outcome of this trial was the percentage of bleeding on probing (BOP) sites. Secondary outcomes were oral parameters, serum reactive oxygen metabolites, antioxidant capacity, oxidative index, concentrations of cytokine (interleukin [IL]-1β, IL-6, IL-10, IL-17, and tumor necrosis factor-alpha) in gingival crevicular fluid, and adverse events. For all parameters, Mann–Whitney U test was used for comparison between experimental and control groups. Analysis of covariance, controlling for baseline periodontal inflamed surface area, was performed to evaluate the association between the effect of the hydrogen-rich jelly and gingival inflammation. Results: In the experiment and control groups, the percentage of sites with BOP and PISA significantly decreased at the end of the experiment compared to the baseline. However, no significant differences were found between groups (p > 0.05). Conclusions: Administration of hydrogen-rich jelly for 14 days decreased gingival inflammation. However, no significant differences were identified compared to the control group.

DOI： 10.3390/healthcare13050577

Efficacy of Oral Intake of Hydrogen-Rich Jelly Intake on Gingival Inflammation: A Double-Blind, Placebo-Controlled and Exploratory Randomized Clinical Trial

Takayuki Maruyama, Eiji Takayama, Shinichi Tokuno, Manabu Morita, Daisuke Ekuni

HEALTHCARE 13 ( 5 ) 2025.3

Language：English Publishing type：Research paper (scientific journal) Publisher：MDPI

Background/Objectives: Initiation and progression of periodontal disease include oxidative stress. Systemic application of antioxidants may provide clinical benefits against periodontal disease including gingivitis. Recently, a jelly containing a high concentration of hydrogen (40 ppm) was developed. We hypothesized that oral intake of this hydrogen-rich jelly may be safe and effective on gingivitis. This clinical trial was designed to investigate the safety and efficacy of oral intake of hydrogen-rich jelly against gingival inflammation. Methods: Participants with gingivitis were instructed to orally ingest 30 g of hydrogen-rich jelly (experimental group) or placebo jelly (control group) three times a day for 14 consecutive days. The primary outcome of this trial was the percentage of bleeding on probing (BOP) sites. Secondary outcomes were oral parameters, serum reactive oxygen metabolites, antioxidant capacity, oxidative index, concentrations of cytokine (interleukin [IL]-1 beta, IL-6, IL-10, IL-17, and tumor necrosis factor-alpha) in gingival crevicular fluid, and adverse events. For all parameters, Mann-Whitney U test was used for comparison between experimental and control groups. Analysis of covariance, controlling for baseline periodontal inflamed surface area, was performed to evaluate the association between the effect of the hydrogen-rich jelly and gingival inflammation. Results: In the experiment and control groups, the percentage of sites with BOP and PISA significantly decreased at the end of the experiment compared to the baseline. However, no significant differences were found between groups (p > 0.05). Conclusions: Administration of hydrogen-rich jelly for 14 days decreased gingival inflammation. However, no significant differences were identified compared to the control group.

DOI： 10.3390/healthcare13050577

Relationship among cancer treatment, quality of life, and oral function in head and neck cancer survivors: A cross-sectional study. Reviewed International journal

Aya Yokoi, Takayuki Maruyama, Reiko Yamanaka, Noriko Takeuchi, Manabu Morita, Daisuke Ekuni

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 32 ( 12 ) 809 - 809 2024.11

Language：English Publishing type：Research paper (scientific journal)

PURPOSE: Treatment for head and neck cancer (HNC), such as surgery and chemoradiotherapy, can reduce oral function and affect quality of life (QoL). However, whether HNC treatment affects QoL via the decline of oral function remains unclear. This study aimed to investigate the relationship among cancer treatment, QoL, and actual oral function in HNC survivors. METHODS: A total of 100 HNC survivors who had completed definitive treatment for HNC at least 6 months prior to enrollment were enrolled in this cross-sectional study. QoL was evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 summary score. Oral diadochokinesis (ODK), tongue pressure, moisture level on the mucosal surface, and mouth opening were measured. Information on age, sex, tumor site, tumor stage, history of HNC treatment, height, body weight, and lifestyle were collected from medical records. Structural equation modeling (SEM) was conducted to analyze the indirect/direct associations among HNC treatment, QoL, and oral function. RESULTS: In total, 100 HNC survivors (58 males and 42 females; age range, 30-81 years, median, 67 years) were analyzed. Overall, 63 patients (63.0%) were diagnosed as oral cancer, 66 (66.0%) developed advanced cancer (stage 3/4), and 58 (58.0%) underwent reconstruction surgery in 100 HNC survivors. The SEM results supported the hypothesized structural model (root mean square error of approximation = 0.044, comparative fit index = 0.990, Tucker-Lewis index = 0.986). Surgery with neck dissection and reconstruction for advanced cancer had indirect effects on lower QoL via ODK and mouth opening. CONCLUSION: HNC treatment is indirectly associated with QoL via oral function in HNC survivors.

DOI： 10.1007/s00520-024-09015-y

Perioperative gum-chewing training prevents a decrease in tongue pressure after esophagectomy in thoracic esophageal cancer patients: a nonrandomized trial Reviewed

Reiko Yamanaka-Kohno, Yasuhiro Shirakawa, Aya Yokoi, Naoaki Maeda, Shunsuke Tanabe, Kazuhiro Noma, Kazuyoshi Shimizu, Toshiharu Mituhashi, Yoshihide Nakamura, Souto Nanba, Yurika Uchida, Takayuki Maruyama, Manabu Morita, Daisuke Ekuni

Scientific Reports 14 ( 1 ) 2024.10

Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media LLC

Abstract

Tongue pressure (TP) decreases significantly after esophagectomy in esophageal cancer patients (ECPs). Meanwhile, 2 weeks of gum-chewing training (GCT) significantly increased TP in healthy university students. We examined whether perioperative GCT would decrease the proportion of patients exhibiting a decline in TP at 2 weeks postoperatively, and prevent postoperative complications, in thoracic ECPs (TECPs). This was a single-center interventional study, and nonrandomized study with a historical control group (HCG). TECPs who underwent first-stage radical esophagectomy were recruited. Thirty-two patients of 40 in the gum-chewing group (GCG) were completed perioperative GCT in 3 times daily. Propensity score matching was performed with covariates related to TP including preoperative age, sex, body mass index, and the repetitive saliva swallowing test result, and yielded a matched cohort of 25 case pairs. Eleven GCG patients [44.0%] exhibited significantly lower TP at 2 weeks postoperatively than before esophagectomy was significantly fewer than that of 19 patients [76.0%] in the HCG. The median number of fever days (> 38 °C) in the 2 weeks after esophagectomy in the GCG was significantly fewer than those in the HCG. Perioperative GCT may prevent postoperative TP decline and postoperative dysphagia-related complications after esophagectomy.

DOI： 10.1038/s41598-024-74090-4

Other Link： https://www.nature.com/articles/s41598-024-74090-4

口腔内のPorphyromonas gingivalis菌数と血清中抗ジンジパイン抗体価の関連性

中村彪雅, 下津尭子, 安居良太, 大廣義幸, 安田多賀子, 丸山貴之, 畑中加珠, 江國大輔, 高柴正悟

臨床化学 53 ( Suppl.1 ) 211 - 211 2024.7

Effect of Antimicrobial Photodynamic Therapy on the Tongue Dorsum on Reducing Halitosis and the Duration of the Effect: A Randomized Clinical Trial. Reviewed International journal

Takayuki Maruyama, Daisuke Ekuni, Aya Yokoi, Junichiro Nagasaki, Nanami Sawada, Manabu Morita

Healthcare (Basel, Switzerland) 12 ( 10 ) 2024.5

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

Antimicrobial photodynamic therapy (PDT) is a treatment that is gaining popularity in modern clinical medicine. However, little is known about the effect of PDT alone on reducing oral halitosis and the duration of the effect. This trial examined the effect of PDT on the tongue dorsum on reducing oral halitosis and the duration of the effect. This study was approved by the Ethics Committee of Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, and Okayama University Hospital (CRB20-015), and it was registered in the Japan Registry of Clinical Trials (jRCTs061200060). Twenty-two participants were randomly assigned to two groups: an intervention group and control group. PDT was performed in the intervention group using red laser emission and methylene blue gel on the middle and posterior area of the tongue dorsum. The concentration of volatile sulfur compounds, bacterial count on the tongue dorsum, probing pocket depth, bleeding on probing, and simplified oral debris index score were determined before and 1 week after PDT. The Mann-Whitney U test was used to assess the significance of the differences in each parameter between the two groups. We found that the hydrogen sulfide concentration and bacterial count on the tongue dorsum were decreased in the intervention group, but there was no statistically significant difference between the two groups. These results indicated that performing only PDT on the tongue dorsum may not contribute to reducing halitosis.

DOI： 10.3390/healthcare12100980

歯周状態と唾液エクソソーム中miRNAとの関係横断研究

澤田ななみ, 福原大樹, 角田伊知郎, 中原桃子, 外山直樹, 横井彩, 竹内倫子, 丸山貴之, 江國大輔

口腔衛生学会雑誌 74 ( 増刊 ) 141 - 141 2024.4

マウスモデルにおける歯周病と糖尿病がアルツハイマー病に与える影響

中原桃子, 福原大樹, Mohammad Nurhamim, Zhang Yixuan, 丸山貴之, 江國大輔

口腔衛生学会雑誌 74 ( 増刊 ) 153 - 153 2024.4

サルコペニアと口腔機能との関連(横断研究)

稲田さくら, 竹内倫子, 澤田ななみ, 外山直樹, 横井彩, 丸山貴之, 角田伊知郎, 福原大樹, 森田学, 江國大輔

口腔衛生学会雑誌 74 ( 1 ) 60 - 60 2024.1

Effects of Bacillus subtilis on periodontitis in a mouse model(タイトル和訳中)

Zhang Yixuan, Mohammad Nurhamim, 中原桃子, 福原大樹, 丸山貴之, 江國大輔

岡山歯学会雑誌 42 ( 2 ) 76 - 76 2023.12

口腔支持療法により外来放射線治療を完遂できた口腔癌3症例

武田斉子, 有村友紀, 田村庄平, 中辻和樹, 三上彩可, 松崎秀信, 丸山貴之, 横井彩, 天野克比古, 水川展吉, 飯田征二

日本口腔ケア学会雑誌 17 ( 3 ) 242 - 242 2023.4

大学生における歯周病発症と受動喫煙を含む危険因子との関係コホート研究

内田悠理香, 江國大輔, 竹内倫子, 丸山貴之, 横井彩, 福原大樹, 福原瑶子, 外山直樹, 澤田ななみ, 中島千穂, 中原桃子, 角田伊知郎, 森田学

口腔衛生学会雑誌 73 ( 増刊 ) 149 - 149 2023.4

大学生における主観的口腔健康評価の傾向と,口腔健康状態および口腔保健行動との関連性

中原桃子, 外山直樹, 江國大輔, 竹内倫子, 丸山貴之, 横井彩, 福原大樹, 澤田ななみ, 中島千穂, 森田学

岡山歯学会雑誌 41 ( 2 ) 61 - 61 2022.12

The Impact of Oral Health Behaviors, Health Belief Model, and Absolute Risk Aversion on the Willingness of Japanese University Students to Undergo Regular Dental Check-Ups: A Cross-Sectional Study Reviewed International journal

Ichiro Sumita, Naoki Toyama, Daisuke Ekuni, Takayuki Maruyama, Aya Yokoi, Daiki Fukuhara, Yoko Uchida-Fukuhara, Momoko Nakahara, Manabu Morita

International Journal of Environmental Research and Public Health 19 ( 21 ) 13920 - 13920 2022.10

Language：English Publishing type：Research paper (scientific journal) Publisher：MDPI AG

Oral health behaviors, risk aversion, and the health belief model are associated with health behaviors. However, there have been few studies that investigated the association between these factors and the willingness to undergo regular dental check-ups. The purpose of this cross-sectional study was to investigate the associations between the willingness of Japanese university students to undergo regular dental check-ups and oral health behaviors, the health belief model, and absolute risk aversion. An analysis was conducted with the cooperation of questionnaire respondents (n = 748) who underwent dental check-ups at Okayama University. The students answered questionnaires on oral health behaviors, the health belief model, absolute risk aversion, and willingness to undergo regular dental check-ups. The logistic regression analysis showed significant positive associations (p < 0.05) between oral health behaviors (use of the inter-dental brush and the dental floss) and the health belief model with the willingness to undergo regular dental check-ups. However, there was no significant association with absolute risk aversion (p > 0.05). These results suggest that willingness to undergo regular dental check-ups was associated with oral health behaviors and the health belief model, but not with absolute risk aversion.

DOI： 10.3390/ijerph192113920

Trends in Self-Rated Oral Health and Its Associations with Oral Health Status and Oral Health Behaviors in Japanese University Students: A Cross-Sectional Study from 2011 to 2019. Reviewed International journal

Momoko Nakahara, Naoki Toyama, Daisuke Ekuni, Noriko Takeuchi, Takayuki Maruyama, Aya Yokoi, Daiki Fukuhara, Nanami Sawada, Yukiho Nakashima, Manabu Morita

International journal of environmental research and public health 19 ( 20 ) 2022.10

Language：English Publishing type：Research paper (scientific journal)

Self-rated oral health (SROH) is a valid, comprehensive indicator of oral health status. The purpose of this cross-sectional study was to analyze how oral health behaviors and clinical oral status were associated with SROH and how they had changed over the course of nine years in Japanese university students. Data were obtained from 17,996 students who underwent oral examinations and completed self-questionnaires from 2011 to 2019. Oral status was assessed using the decayed and filled teeth scores, bleeding on probing (BOP), probing pocket depth, the Oral Hygiene Index-Simplified (OHI-S), oral health behaviors, and related factors. SROH improved from 2011 to 2019. The logistic regression model showed that university students who were female and had a high daily frequency of tooth brushing, no BOP, no decayed teeth, no filled teeth, and a low OHI-S score and were significantly more likely to report very good, good, or fair SROH. An interaction effect was observed between survey year and regular dental check-ups (year × regular dental check-ups). The improvement trend in SROH might be associated with changes in oral health behaviors and oral health status.

DOI： 10.3390/ijerph192013580

Relationship between Psychological Stress Determined by Voice Analysis and Periodontal Status: A Cohort Study. Reviewed International journal

Takayuki Maruyama, Daisuke Ekuni, Masakazu Higuchi, Eiji Takayama, Shinichi Tokuno, Manabu Morita

International journal of environmental research and public health 19 ( 15 ) 2022.8

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

In modern society, evaluation and management of psychological stress may be important for the prevention of periodontal disease. The purpose of this study was to examine the relationship between psychological stress (vitality and mental activity) evaluated by Mind Monitoring System (MIMOSYS) and periodontal status. Forty students of Okayama University underwent the oral examination and self-reported questionnaire on the first day (baseline) and the 14th day (follow-up). Voice recording was performed every day with the MIMOSYS app during the whole study period. The participants completed the Patient Health Questionnaire (PHQ)-9 and Beck Depression Inventory (BDI) at baseline and at follow-up. Spearman's rank correlation coefficient was used to determine the significance of correlations among variables. The PHQ-9 and BDI scores were negatively correlated with vitality in the morning. Change in vitality in the morning was significantly correlated with changes in periodontal inflammation. Mental activity was significantly correlated with change in mean probing pocket depth. This result shows that measurement of psychological stress using a voice-based tool to assess mental health may contribute to the early detection of periodontal disease.

DOI： 10.3390/ijerph19159489

Association between serum miRNAs and gingival gene expression in an obese rat model Reviewed

Takayuki Maruyama, Terumasa Kobayashi, Yoshio Sugiura, Toshiki Yoneda, Daisuke Ekuni, Manabu Morita

Journal of Periodontal Research 57 ( 3 ) 502 - 509 2022.6

Authorship：Lead author Publishing type：Research paper (scientific journal)

Introduction: Recent studies have reported a relationship between periodontitis and obesity; however, the mechanisms of obesity’s effects on periodontitis are not well understood. On the other hand, microRNAs (miRNAs) are known to play key roles in the post-transcriptional regulation gene expression by suppressing translation and protein synthesis. We examined the association between obesity-related miRNAs and gene expression in gingival tissue using miRNA–messenger RNA (mRNA) pairing analysis in an obese rat model. Methods: Sixteen male Wistar rats aged 8 weeks old were divided into two groups: the control group was fed a normal powdered food for 8 weeks, and the obesity group was fed a high-fat diet for 8 weeks. Distance from the cement–enamel junction to the alveolar bone crest of the first molars was measured. miRNA microarray analysis was performed on samples of serum and gingival tissue; the resulting data were used to calculate fold changes in miRNA levels in the obesity group relative to the control group, and miRNA–mRNA pairing analysis was performed to identify mRNAs potentially targeted by miRNAs of interest. Results: Alveolar bone loss in the obesity group exceeded that in the control group (p =.017). miRNA–mRNA pairing analysis identified an association between 4 miRNAs (miR-759, miR-9a-3p, miR-203b-3p, and miR-878) that were differentially expressed in the obesity and control groups and 7 genes (Ly86, Arid5b, Rgs18, Mlana, P2ry13, Kif1b, and Myt1) expressed in gingival tissue. Conclusion: This study revealed that several miRNAs play an important role in the mechanism of periodontal disease progression induced by the obesity.

DOI： 10.1111/jre.12979

コロナ禍前とコロナ禍における大学生の睡眠時ブラキシズムの検討(横断研究)

江國大輔, 丸山貴之, 横井彩, 福原大樹, 外山直樹, 澤田ななみ, 中原桃子, 角田伊知郎, 森田学

口腔衛生学会雑誌 72 ( 増刊 ) 79 - 79 2022.4

周術期のガム咀嚼トレーニングは胸部食道がん患者の咀嚼能力を維持・向上させる

山中玲子, 白川靖博, 横井彩, 中村吉秀, 難波奏人, 田辺俊介, 野間和広, 清水一好, 内田悠理香, 吉冨愛子, 丸山貴之, 江國大輔, 森田学

口腔衛生学会雑誌 72 ( 増刊 ) 101 - 101 2022.4

舌背への光線力学療法による口臭の改善効果の検討ランダム化比較試験

長崎潤一郎, 丸山貴之, 横井彩, 江國大輔, 澤田ななみ, 森田学

口腔衛生学会雑誌 72 ( 増刊 ) 81 - 81 2022.4

大学病院における口腔ケア岡山大学病院頭頸部がんセンターにおける顎骨再建後のインプラントと口腔ケアの重要性

水川展吉, 武田斉子, 木股敬裕, 松本洋, 安藤瑞生, 丸山貴之, 佐々木禎子, 田中祐貴, 上田明広, 飯田征二

日本口腔ケア学会雑誌 16 ( 3 ) 83 - 83 2022.4

家庭での毎日の受動喫煙曝露は大学生の歯周病と関係する(横断研究)

江國大輔, 竹内倫子, 丸山貴之, 横井彩, 福原大樹, 外山直樹, イスラム・モハマド・モニルル, 澤田ななみ, 中原桃子, 中島千穂, 出口純也, 福原瑶子, 森田学

口腔衛生学会雑誌 72 ( 1 ) 54 - 54 2022.1

岡山大学新入生の口腔健康状態および主観的口腔健康評価の9年間の変化

中原桃子, 外山直樹, 江國大輔, 竹内倫子, 丸山貴之, 横井彩, 福原大樹, イスラム・モハマド・モニルル, 澤田ななみ, 中島千穂, 出口純也, 森田学

口腔衛生学会雑誌 72 ( 1 ) 54 - 54 2022.1

Detection of Salivary miRNAs That Predict Chronic Periodontitis Progression: A Cohort Study. Reviewed International journal

Kohei Fujimori, Toshiki Yoneda, Takaaki Tomofuji, Daisuke Ekuni, Tetsuji Azuma, Takayuki Maruyama, Yoshio Sugiura, Manabu Morita

International journal of environmental research and public health 18 ( 15 ) 2021.7

Language：English Publishing type：Research paper (scientific journal)

The aim of this two-year cohort study was to investigate salivary microRNAs (miRNAs) that predict periodontitis progression. A total of 120 patients who underwent supportive periodontal therapy were recruited. Unstimulated whole saliva was collected at baseline. Two years later, 44 patients were followed up (median age, 67.1 years) and divided into two groups: progression group (n = 22), with one or more sites with clinical attachment level (CAL) progression (>3 mm compared with baseline) or tooth extraction due to periodontitis progression; and the control group (n = 22), which did not exhibit CAL progression. In the microarray analysis of salivary miRNAs, hsa-miR-5571-5p, hsa-miR-17-3p, hsa-let-7f-5p, hsa-miR-4724-3p, hsa-miR-99a-5p, hsa-miR-200a-3p, hsa-miR-28-5p, hsa-miR-320d, and hsa-miR-31-5p showed fold change values <0.5 or ≥2.0 in the progression group compared with the control group (p < 0.05). On receiver operating characteristic curve analysis, areas under the curves of hsa-miR-5571-5p, hsa-let-7f-5p, hsa-miR-99a-5p, hsa-miR-28-5p, and hsa-miR-320d were >0.7, indicating fair discrimination power. The expressions of salivary hsa-miR-5571-5p, hsa-let-7f-5p, hsa-miR-99a-5p, hsa-miR-28-5p, and hsa-miR-320d were associated with periodontitis progression in patients with chronic periodontitis. These salivary miRNAs may be new biomarkers for progression of periodontitis, and monitoring them may contribute to new diagnostics and precision medicine for periodontitis.

DOI： 10.3390/ijerph18158010

Parafunctional masseter muscle activity during waking is related to periodontitis progression: A pilot prospective cohort study. Reviewed International journal

Daisuke Ekuni, Seiya Kato, Shigehisa Kawakami, Takayuki Maruyama, Kota Kataoka, Yoko Uchida-Fukuhara, Daiki Fukuhara, Naoki Toyama, Aya Yokoi, Md Monirul Islam, Subrina Binta Khair, Naoki Kodama, Manabu Morita

Journal of clinical periodontology 48 ( 6 ) 785 - 794 2021.6

Language：English Publishing type：Research paper (scientific journal) Publisher：Wiley

AIM: The purpose of this pilot prospective cohort study was to investigate the effects of parafunctional masseter muscle activity on periodontitis progression among patients receiving supporting periodontal therapy (SPT). MATERIALS AND METHODS: We collected data of patients treated at Okayama University Hospital from August 2014 to September 2018. The progression group was defined as patients with ≥2 teeth demonstrating a longitudinal loss of proximal attachment of ≥3 mm during the 3-year study period and/or at least one tooth extraction due to periodontitis progression. Surface electromyography of masseter muscles at baseline was continuously recorded while patients were awake and asleep. RESULTS: We analysed 48 patients (36 females) aged 66.8 ± 9.1 years (mean ± SD). The rate of parafunctional masseter muscle activity during waking hours and sleeping hours at baseline was 60.4% and 52.1%, respectively. Cox's proportional hazards regression model showed that the incidence of periodontitis progression was significantly associated with number of teeth present (p = 0.001) and parafunctional masseter muscle activity during waking hours (p = 0.041). CONCLUSION: Our results suggest that parafunctional masseter muscle activity during waking hours is a risk factor for periodontitis progression among patients receiving SPT.

DOI： 10.1111/jcpe.13432

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/jcpe.13432

噛みたばこ習慣のあるミャンマーでの口腔がん検診

水川展吉, Swe Swe Win, 加藤昌, 丸山貴之, 山近英樹, 木股敬裕, 飯田征二

頭頸部癌 47 ( 2 ) 244 - 244 2021.5

「口臭による日常生活への支障」に関連する要因

佐保輝, 横井彩, 丸山貴之, 竹内倫子, 江國大輔, 森田学

日本口臭学会会誌 12 ( 1 ) 11 - 17 2021.5

Language：Japanese Publisher：日本口臭学会

本調査の目的は、自己記入式質問票の「社会生活への支障」「家庭生活への支障」「行動制限」「自身の口臭が原因による他人の嫌がる態度やジェスチャー」の4項目を「口臭による日常生活への支障」と定義しその実態を把握すること、および、「口臭による日常生活への支障」と関連する要因について検討することである。2018年1月から2020年1月までの間に岡山大学病院口臭専門外来を受診した全患者32名(男性12名、女性20名、平均年齢53.2±16.2歳)を対象とした。オーラルクロマ(NISSHAエフアイエス株式会社、大阪)を用い、口腔内の揮発性硫黄化合物の濃度を測定した。自己記入式の質問票を用いて、上記4項目のほかに年齢、性別、口臭を意識するようになったきっかけ、口臭を意識した時期、頻回の歯磨き・うがい薬の使用・舌磨きによる口臭対策、医療者への相談経験を調査した。なお、口臭による日常生活への支障については、「社会生活への支障」「家庭生活への支障」「行動制限」「自身の口臭が原因による他人の嫌がる態度やジェスチャー」の各質問に対する回答【はい(1点)/いいえ(0点)】をもとに、合計スコア0〜4点で評価した。各質問項目との関連についてSpearmanの順位相関係数とカイ二重検定を用いて検討した。有意水準は5%とした。その結果、本調査で定義した「口臭による日常生活への支障」を有する患者が87.5%存在した。その支障の程度が大きい者は、長期にわたって口臭を意識しており、医療者への相談や複数の口臭対策を行っていた。一方で、実際の口腔内の揮発性硫黄化合物の濃度は有意に低いことが明らかになった。本調査結果は、口臭専門外来における新たな視点を提供する可能性がある。(著者抄録)

「口臭による日常生活への支障」に関連する要因

佐保輝, 横井彩, 丸山貴之, 竹内倫子, 江國大輔, 森田学

日本口臭学会会誌 12 ( 1 ) 49 - 50 2021.5

岡山大学病院頭頸部がんセンターにおける頭頸部がん支持療法に関する臨床実習教育の取り組みについて

丸山貴之, 横井彩, 中原桃子, 佐々木禎子, 梶谷明子, 藤代万由, 中本美保, 吉田陽子, 森田学, 三浦留美, 山中玲子, 水川展吉, 浅海淳一, 安藤瑞生, 木股敬裕

日本口腔ケア学会雑誌 15 ( 3 ) 186 - 186 2021.4

ヘルスリテラシーとリスク選好が定期的な歯科健診への受診意志に与える影響

角田伊知郎, 森田学, 江國大輔, 丸山貴之, 片岡広太, 横井彩, 福原大樹, 福原瑶子, 外山直樹, 中原桃子

口腔衛生学会雑誌 71 ( 増刊 ) 88 - 88 2021.4

頭頸部がん治療による口腔機能・QOLへの影響縦断研究

横井彩, 丸山貴之, 中原桃子, 山中玲子, 江國大輔, 森田学

口腔衛生学会雑誌 71 ( 増刊 ) 116 - 116 2021.4

岡山大学病院頭頸部がんセンターにおけるエピシル使用経験について

武田斉子, 水川展吉, 田村庄平, 岡田亜由美, 中田靖章, 横井彩, 丸山貴之, 松崎秀信, 松崎久美子, 藤代万由, 佐々木禎子, 山中玲子, 安藤瑞生, 木股敬裕, 浅海淳一, 飯田征二

日本口腔ケア学会雑誌 15 ( 3 ) 172 - 172 2021.4

Effects of Coffee Intake on Oxidative Stress During Aging-related Alterations in Periodontal Tissue Reviewed

TERUMASA KOBAYASHI, TAKAYUKI MARUYAMA, TOSHIKI YONEDA, HISATAKA MIYAI, TETSUJI AZUMA, TAKAAKI TOMOFUJI, DAISUKE EKUNI, MANABU MORITA

In Vivo 34 ( 2 ) 615 - 622 2020.3

慢性歯周炎患者の歯周状態の悪化に関連する唾液中miRNAの探索コホート研究

藤森浩平, 米田俊樹, 杉浦嘉雄, 丸山貴之, 江國大輔, 東哲司, 友藤孝明, 森田学

口腔衛生学会雑誌 70 ( 増刊 ) 158 - 158 2020.3

Detection of Serum miRNAs Affecting Liver Apoptosis in a Periodontitis Rat Model Reviewed

YOSHIO SUGIURA, TOSHIKI YONEDA, KOHEI FUJIMORI, TAKAYUKI MARUYAMA, HISATAKA MIYAI, TERUMASA KOBAYASHI, DAISUKE EKUNI, TAKAAKI TOMOFUJI, MANABU MORITA

In Vivo 34 ( 1 ) 117 - 123 2020.1

Relationship between acetaldehyde concentration in mouth air and characteristics of microbiota of tongue dorsum in Japanese healthy adults: a cross-sectional study. Reviewed International journal

Aya Yokoi, Daisuke Ekuni, Hironobu Hata, Mayu Yamane-Takeuchi, Takayuki Maruyama, Reiko Yamanaka, Manabu Morita

Journal of applied oral science : revista FOB 27 e20180635 2019.6

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: Acetaldehyde, associated with consumption of alcoholic beverages, is known to be a carcinogen and to be related to the tongue dorsum. The aim of this study was to investigate the relationship between acetaldehyde concentration in mouth air and bacterial characteristics on the tongue dorsum. METHODOLOGY: Thirty-nine healthy volunteers participated in the study. Acetaldehyde concentrations in mouth air were evaluated by a high-sensitivity semiconductor gas sensor. A 16S rRNA gene sequencing technique was used to compare microbiomes between two groups, focusing on the six samples with the highest acetaldehyde concentrations (HG) and the six samples with lowest acetaldehyde concentrations (LG). RESULTS: Acetaldehyde concentration increased in correlation with the increase in bacterial count (p=0.048). The number of species observed in the oral microbiome of the HG was higher than that in the oral microbiome of the LG (p=0.011). The relative abundances of Gemella sanguinis, Veillonella parvula and Neisseria flavescens in the oral microbiome of the HG were higher than those in the oral microbiome of the LG (p<0.05). CONCLUSION: Acetaldehyde concentration in mouth air was associated with bacterial count, diversity of microbiome, and relative abundance of G. sanguinis, V. parvula, and N. flavescens.

DOI： 10.1590/1678-7757-2018-0635

Serum microRNAs and chronic periodontitis: A case-control study. Reviewed International journal

Toshiki Yoneda, Takaaki Tomofuji, Daisuke Ekuni, Tetsuji Azuma, Takayuki Maruyama, Kohei Fujimori, Yoshio Sugiura, Manabu Morita

Archives of oral biology 101 57 - 63 2019.5

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: An association is present between periodontitis and rates of expression of certain microRNAs (miRNAs) in periodontal tissue. However, the association between periodontitis and miRNA levels in human serum is unknown. We performed a case-control study in patients with chronic periodontitis to investigate serum miRNA levels. DESIGN: We enrolled 30 healthy patients without periodontitis and 30 patients with chronic periodontitis. Participants underwent clinical examination, case selection, and a blood draw from the antecubital vein. Serum miRNA profiles were compared in samples from participants with and without chronic periodontitis using microarray and real-time PCR. RESULTS: Microarray demonstrated seven miRNAs that were expressed <1/1.5 or >1.5 in the control group compared to the periodontitis group (p < 0.05). Real-time PCR showed that hsa-miR-664a-3p, hsa-miR-501-5p, and hsa-miR-21-3p were higher in the periodontitis group than the control group (p < 0.05). CONCLUSION: Hsa-miR-664a-3p, hsa-miR-501-5p, and hsa-miR-21-3p are candidate serum biomarkers for chronic periodontitis.

DOI： 10.1016/j.archoralbio.2019.03.009

Detection of Salivary miRNAs Reflecting Chronic Periodontitis: A Pilot Study. Reviewed International journal

Kohei Fujimori, Toshiki Yoneda, Takaaki Tomofuji, Daisuke Ekuni, Tetsuji Azuma, Takayuki Maruyama, Hirofumi Mizuno, Yoshio Sugiura, Manabu Morita

Molecules (Basel, Switzerland) 24 ( 6 ) 2019.3

Language：English Publishing type：Research paper (scientific journal)

The purpose of this cross-sectional pilot study was to find salivary microRNAs (miRNAs) reflecting periodontal condition in chronic periodontitis. One hundred and twenty chronic periodontitis patients (mean age, 68.4 years) participated in the study, from whom unstimulated whole saliva was collected. A multiphase study was conducted to explore salivary miRNAs as biomarkers of periodontitis. At first, a polymerase chain reaction (PCR) array was performed to compare salivary miRNAs profiles in no and mild (no/mild) and severe periodontitis patients. Next, the relative expression of salivary miRNAs on individual samples was assessed by real-time reverse transcription-PCR. The numbers (%) of patients were 26 (21.6%, no/mild), 58 (48.3%, moderate) and 36 (30.0%, severe), respectively. Among 84 miRNAs, only the relative expression of hsa-miR-381-3p in the severe periodontitis group was significantly higher than that of the no/mild periodontitis group (p < 0.05). Among the 120 patients, there was also a significant correlation between the relative expression of hsa-miR-381-3p and the mean probing pocket depth (PPD) (r = 0.181, p < 0.05). Salivary hsa-miR-381-3p was correlated with periodontitis condition in chronic periodontitis patients.

DOI： 10.3390/molecules24061034

Relationship Between Renal Dysfunction and Oral Mucositis in Patients Undergoing Concurrent Chemoradiotherapy for Pharyngeal Cancer: A Retrospective Cohort Study. Reviewed

Mizuno H, Miyai H, Yokoi A, Kobayashi T, Inabu C, Maruyama T, Ekuni D, Mizukawa N, Kariya S, Nishizaki K, Kimata Y, Morita M

In vivo (Athens, Greece) 33 ( 1 ) 183 - 189 2019.1

New oral hygiene care regimen reduces postoperative oral bacteria count and number of days with elevated fever in ICU patients with esophageal cancer. Reviewed

Hirofumi Mizuno, Shinsuke Mizutani, Daisuke Ekuni, Ayano Tabata-Taniguchi, Takayuki Maruyama, Aya Yokoi, Chie Omori, Kazuyoshi Shimizu, Hiroshi Morimatsu, Yasuhiro Shirakawa, Manabu Morita

Journal of oral science 60 ( 4 ) 536 - 543 2018.12

Language：English Publishing type：Research paper (scientific journal)

Using a controlled pre/post study design, we investigated the effects of professional mechanical cleaning of the oral cavity with benzethonium chloride, interdental brushes, and hydrogen peroxide on the number of oral bacteria and postoperative complications among esophageal cancer patients in an intensive care unit. Before surgery, 44 patients with esophageal cancer were recruited at Okayama Hospital from January through August 2015. The control group (n = 23) received routine oral hygiene care in the intensive care unit. The intervention group (n = 21) received intensive interdental cleaning with benzethonium chloride solution and tongue cleaning with hydrogen peroxide. The number of oral bacteria on the tongue surface and plaque index were significantly lower in the intervention group than in the control group on postoperative days 1 and 2 (P < 0.05). Additionally, the number of days with elevated fever during a 1-week period was significantly lower in the intervention group than in the control group (P = 0.037). As compared with routine oral hygiene, a new oral hygiene regimen comprising benzethonium chloride, interdental brushes, and hydrogen peroxide significantly reduced the number of oral bacteria and days with elevated fever in patients with esophageal cancer.

DOI： 10.2334/josnusd.17-0381

The effects of non-surgical periodontal treatment on glycemic control, oxidative stress balance and quality of life in patients with type 2 diabetes: A randomized clinical trial. Reviewed International journal

Hirofumi Mizuno, Daisuke Ekuni, Takayuki Maruyama, Kota Kataoka, Toshiki Yoneda, Daiki Fukuhara, Yoshio Sugiura, Takaaki Tomofuji, Jun Wada, Manabu Morita

PloS one 12 ( 11 ) e0188171 2017.11

Language：English Publishing type：Research paper (scientific journal) Publisher：PUBLIC LIBRARY SCIENCE

Aim
The purpose of this study was to investigate the effects of non-surgical periodontal treatment on hemoglobinA1c (HbA1c) levels, oxidative stress balance and quality of life (QOL) in patients with type 2 diabetes mellitus (T2DM) compared to no periodontal treatment (simple oral hygiene instructions only).
Methods
The design was a 6-month, single-masked, single center, randomized clinical trial. Patients had both T2DM and chronic periodontitis. Forty participants were enrolled between April 2014 and March 2016 at the Nephrology, Diabetology and Endocrinology Department of Okayama University Hospital. The periodontal treatment group (n = 20) received non-surgical periodontal therapy, including scaling and root planing plus oral hygiene instructions, and consecutive supportive periodontal therapy at 3 and 6 months. The control group (n = 17) received only oral hygiene instructions without treatment during the experimental period. The primary study outcome was the change in HbA1c levels from baseline to 3 months. Secondary outcomes included changes in oxidative stress balance (Oxidative-INDEX), the Diabetes Therapy-Related QOL and clinical periodontal parameters from baseline to 3 months and baseline to 6 months.
Results
Changes in HbA1c in the periodontal treatment group were not significantly different with those in the control group at 3 and 6 months. Systemic oxidative stress balance and QOL significantly improved in the periodontal treatment group compared to the control group at 3 months. In the subgroup analysis (moderately poor control of diabetes), the decrease in HbA1c levels in the periodontal treatment group was greater than that in the control group at 3 months but not significant.
Conclusions
In T2DM patients, non-surgical periodontal treatment improved systemic oxidative stress balance and QOL, but did not decrease HbA1c levels at 3 months follow-up.

DOI： 10.1371/journal.pone.0188171

Topical application of ointment containing 0.5% green tea catechins suppresses tongue oxidative stress in 5-fluorouracil administered rats. Reviewed International journal

Hisataka Miyai, Takayuki Maruyama, Takaaki Tomofuji, Toshiki Yoneda, Tetsuji Azuma, Hirofumi Mizuno, Yoshio Sugiura, Terumasa Kobayashi, Daisuke Ekuni, Manabu Morita

Archives of oral biology 82 247 - 255 2017.10

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal) Publisher：PERGAMON-ELSEVIER SCIENCE LTD

Objective: The purpose of this study was to investigate the preventive effects of topical application of green tea catechins on tongue oxidative stress induced by 5-fluorouracil (5-FU) administration in rats.
Design: Male Wistar rats (n = 28, 8 weeks old) were divided into four groups of seven rats each: a negative control group (saline administration and application of ointment without green tea catechins), a positive control group (5-FU administration and application of ointment without green tea catechins), and two experimental groups (5-FU administration and application of ointment containing 0.1% or 0.5% green tea catechins). Topical application of each ointment to the ventral surface of the tongue was performed once a day for 5 days. The level of 8-hydroxydeoxyguanosine (8-OHdG) was determined to evaluate oxidative stress. Fluorescence staining was also performed to confirm nuclear factor erythroid 2-related factor 2 (Nrf2) translocation to the nucleus.
Results: After the experimental period, the ratios of 8-OHdG-positive cells in the ventral tongue tissue were higher in the positive control group than in the negative control group (P < 0.05). On the other hand, those in the 0.5% green tea catechin group, but not in the 0.1% green tea catechin group, were lower than the positive control group (P < 0.05). In addition, Nrf2 translocation to the nucleus was greater in the 0.5% green tea catechin group than in the positive control group (P < 0.05).
Conclusions: Topical application of ointment containing 0.5% green tea catechins could prevent tongue oxidative stress in 5-FU administered rats, via up-regulation of the Nrf2 signaling pathway.

DOI： 10.1016/j.archoralbio.2017.06.025

Expression of Salivary miR-203a-3p Was Related with Oral Health-Related Quality of Life in Healthy Volunteers. Reviewed International journal

Terumasa Kobayashi, Takaaki Tomofuji, Tatsuya Machida, Toshiki Yoneda, Daisuke Ekuni, Tetsuji Azuma, Takayuki Maruyama, Akiko Hirose, Manabu Morita

International journal of molecular sciences 18 ( 6 ) 2017.6

Language：English Publishing type：Research paper (scientific journal) Publisher：MDPI AG

Oral health-related quality of life (OHRQoL) is a multidimensional construct that involves subjective evaluation of an individual's oral health. Although it is difficult to evaluate OHRQoL biologically, recently, it has been reported that circulating microRNAs (miRNAs) in several body fluids could reflect various health conditions. The aim of this pilot study was to investigate whether salivary miRNAs expression differs according to OHRQoL in healthy volunteers. Forty-six volunteers (median age, 23.0 years) were recruited, and their OHRQoL was assessed using the Japanese version of the Oral Health Impact Profile (OHIP-J). Then, we compared salivary microRNA profiles of the high-OHRQoL group (<= 25th percentile score of OHIP-J) and the low-OHRQoL group (>= 75th percentile score of OHIP-J) using the polymerase chain reaction (PCR) array and the quantitative real-time PCR. There were no significant differences between the two groups in terms of oral health status. In the PCR array, miR-203a-3p and miR-30b-5p were significantly more expressed in the low-OHRQoL group (p < 0.05). Quantitative real-time PCR assay also showed that miR-203a-3p was more highly expressed in the low-OHRQoL group than in the high-OHRQoL group (p < 0.05). These observations suggest that expression of salivary miR-203a-3p was related with OHRQoL in healthy volunteers.

DOI： 10.3390/ijms18061263

Association between periodontitis and prognosis of pancreatobiliary tract cancer: A pilot study. Reviewed International journal

Takayuki Maruyama, Takaaki Tomofuji, Tatsuya Machida, Hironari Kato, Koichiro Tsutsumi, Daisuke Uchida, Akinobu Takaki, Toshiki Yoneda, Hisataka Miyai, Hirofumi Mizuno, Daisuke Ekuni, Hiroyuki Okada, Manabu Morita

Molecular and clinical oncology 6 ( 5 ) 683 - 687 2017.5

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)

Several studies have indicated that periodontitis is a risk factor for cancer. However, the association between periodontitis and the prognosis of pancreatobiliary tract cancer remains unclear. The aim of this pilot study was to investigate the association between periodontitis and prognosis of pancreatobiliary tract cancer. A total of 22 patients diagnosed with pancreatobiliary tract cancer were analyzed. Oral health status, including severity of periodontitis, general health status and biochemical serum markers were evaluated. The Kaplan-Meier method and Cox proportional hazards model were used to assess factors affecting the prognosis of pancreatobiliary tract cancer. The Kaplan-Meier analysis demonstrated that low body mass index, high concentration of serum C-reactive protein (CRP) and severe periodontitis were significant prognostic factors for survival rate. The Cox proportional hazards model revealed that serum carbohydrate antigen 19-9 concentration [hazard ratio (HR)=1.002; 95% confidence interval (CI): 1.000-1.004] and serum CRP concentration (HR=2.57; 95% CI: 1.15-5.74) were significantly associated with the prognosis of pancreatobiliary tract cancer. In addition, cancer patients with severe periodontitis had higher serum CRP concentrations compared with those without severe periodontitis. Therefore, severe periodontitis indirectly affected the prognosis of pancreatobiliary tract cancer through promoting systemic inflammation.

DOI： 10.3892/mco.2017.1220

The Serum Oxidative/Anti-oxidative Stress Balance Becomes Dysregulated in Patients with Non-alcoholic Steatohepatitis Associated with Hepatocellular Carcinoma. Reviewed

Yasuyuki Shimomura, Akinobu Takaki, Nozomu Wada, Tetsuya Yasunaka, Fusao Ikeda, Takayuki Maruyama, Naofumi Tamaki, Daisuke Uchida, Hideki Onishi, Kenji Kuwaki, Shinichiro Nakamura, Kazuhiro Nouso, Yasuhiro Miyake, Kazuko Koike, Takaaki Tomofuji, Manabu Morita, Kazuhide Yamamoto, Hiroyuki Okada

Internal medicine (Tokyo, Japan) 56 ( 3 ) 243 - 251 2017

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN SOC INTERNAL MEDICINE

Objective Oxidative stress is associated with the progression of chronic liver disease. Non-alcoholic fatty liver disease (NAFLD) is also an oxidative stress-related disease. However, the oxidative/anti-oxidative balance has not been fully characterized in NAFLD. The objective of the present study was to investigate the balance between oxidative stress and the anti-oxidative activity in NAFLD, including non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC).
Patients We recruited 69 patients with histologically proven NAFLD without HCC (NAFLD; n=58), and with NASH-related HCC (NASH-HCC; n=11). The 58 NAFLD patients included patients with non-alcoholic fatty liver (NAFL; n=14) and NASH (n=44).
Methods The serum levels of reactive oxygen metabolites (ROM) and anti-oxidative markers (OXY) were determined and then used to calculate the oxidative index. The correlations among such factors as ROM, OXY, oxidative index, and clinical characteristics were investigated.
Results In NAFLD, ROM positively correlated with the body mass index (BMI), hemoglobin A1c (HbA1c), C-reactive protein (CRP), and the histological grade or inflammatory scores, while only high HbA1c and CRP levels were significant factors that correlated with a higher ROM according to a multivariate analysis. OXY positively correlated with the platelet counts, albumin, and creatinine levels, while negatively correlating with age. However, it improved after treatment intervention. The oxidative index positively correlated with BMI, CRP, and HbA1c. The NASH-HCC patients exhibited a lower OXY than the NASH patients, probably due to the effects of aging.
Conclusion Oxidative stress correlated with the levels of NASH activity markers, while the anti-oxidative function was preserved in younger patients as well as in patients with a well-preserved liver function. The NASH-HCC patients tended to be older and exhibited a diminished anti-oxidative function.

DOI： 10.2169/internalmedicine.56.7002

miR‑1246 and miR‑4644 in salivary exosome as potential biomarkers for pancreatobiliary tract cancer. Reviewed International journal

Tatsuya Machida, Takaaki Tomofuji, Takayuki Maruyama, Toshiki Yoneda, Daisuke Ekuni, Tetsuji Azuma, Hisataka Miyai, Hirofumi Mizuno, Hironari Kato, Koichiro Tsutsumi, Daisuke Uchida, Akinobu Takaki, Hiroyuki Okada, Manabu Morita

Oncology reports 36 ( 4 ) 2375 - 81 2016.10

Language：English Publishing type：Research paper (scientific journal) Publisher：SPANDIDOS PUBL LTD

Pancreatobiliary tract cancer is a highly fatal cancer. Detection of pancreatobiliary tract cancer is difficult because it lacks typical clinical symptoms and because of its anatomical location. Biomarker discovery is therefore important to detect pancreatobiliary tract cancer in its early stage. A study demonstrated that expression levels of miR-1246, miR-3976, miR-4306, and miR-4644 in serum exosomes were higher in pancreatic cancer patients than these levels in healthy control participants. Supposing that microRNA (miRNA) expression profiles in saliva are similar to those in serum, four miRNAs (miR-1246, miR-3976, miR-4306, and miR-4644) in salivary exosomes may also be useful for detection of pancreatobiliary tract cancer. In this study, it was examined whether these miRNAs could be used as biomarkers for pancreatobiliary tract cancer. Twelve pancreatobiliary tract cancer patients and 13 healthy control participants were analyzed as a cancer and a control group, respectively. Unstimulated whole saliva was collected, salivary exosomes were isolated, and total RNA was extracted. Using quantitative real-time PCR (RT-qPCR), the relative expression ratios of miR-1246 and miR-4644 were significantly higher in the cancer group than these ratios in the control group. Receiver operating characteristic (ROC) curves were constructed to analyze the discrimination power of these miRNAs. For miR-1246, the results yielded an area under the curve (AUC) of 0.814 (P=0.008). For miR-4644, the results yielded an AUC of 0.763 (P=0.026). For the combination of miR-1246 and miR-4644, the results yielded an increased AUC of 0.833 (P=0.005). This pilot study suggests that miR-1246 and miR-4644 in salivary exosomes could be candidate biomarkers for pancreatobiliary tract cancer.

DOI： 10.3892/or.2016.5021

Oxidative stress balance is dysregulated and represents an additional target for treating cholangiocarcinoma. Reviewed International journal

Daisuke Uchida, Akinobu Takaki, Hisashi Ishikawa, Yasuko Tomono, Hironari Kato, Koichiro Tsutsumi, Naofumi Tamaki, Takayuki Maruyama, Takaaki Tomofuji, Ryuichiro Tsuzaki, Tetsuya Yasunaka, Kazuko Koike, Hiroshi Matsushita, Fusao Ikeda, Yasuhiro Miyake, Hidenori Shiraha, Kazuhiro Nouso, Ryuichi Yoshida, Yuzo Umeda, Susumu Shinoura, Takahito Yagi, Toshiyoshi Fujiwara, Manabu Morita, Masaki Fukushima, Kazuhide Yamamoto, Hiroyuki Okada

Free radical research 50 ( 7 ) 732 - 43 2016.7

Language：English Publishing type：Research paper (scientific journal) Publisher：TAYLOR & FRANCIS LTD

Background: Pancreatico-biliary malignancies exhibit similar characteristics, including obesity-related features and poor prognosis, and require new treatment strategies. Oxidative stress is known to induce DNA damage and carcinogenesis, and its reduction is viewed as being favorable. However, it also has anti-infection and anti-cancer functions that need to be maintained. To reveal the effect of oxidative stress on cancer progression, we evaluated oxidative stress and anti-oxidative balance in pancreatic cancer (PC) and cholangiocarcinoma (CC) patients, as well as the effect of add-on antioxidant treatment to chemotherapy in a mouse cholangiocarcinoma model.
Methods: We recruited 84 CC and 80 PC patients who were admitted to our hospital. Serum levels of reactive oxygen metabolites (ROM) and the anti-oxidative OXY-adsorbent test were determined and the balance of these tests was defined as an oxidative index. A diabetic mouse-based cholangiocarcinoma model was utilized to evaluate the effects of add-on antioxidant therapy on cholangiocarcinoma chemotherapy.
Results: Serum ROM was higher and anti-oxidant OXY was lower in CC patients with poor outcomes. These parameters were not significantly different in PC patients. In mice, vitamin E administration induced antioxidant hemeoxygenase (HO)-1 protein expression in cancer tissue, while the number of stem-like cells increased. L-carnitine administration improved intestinal microbiome and biliary acid balance, upregulated the hepatic mitochondrial membrane uptake related gene Cpt1 in non-cancerous tissue, and did not alter stem-like cell numbers.
Conclusion: Oxidative stress balance was dysregulated in cholangiocarcinoma with poor outcome. The mitochondrial function-supporting agent L-carnitine is a good candidate to control oxidative stress conditions.

DOI： 10.3109/10715762.2016.1172071

MicroRNAs as serum biomarkers for periodontitis. Reviewed International journal

Takaaki Tomofuji, Toshiki Yoneda, Tatsuya Machida, Daisuke Ekuni, Tetsuji Azuma, Kota Kataoka, Takayuki Maruyama, Manabu Morita

Journal of clinical periodontology 43 ( 5 ) 418 - 25 2016.5

Language：English Publishing type：Research paper (scientific journal) Publisher：WILEY-BLACKWELL

Aim: Studies demonstrated that periodontitis modulates microRNA (miRNAs) expression rates in periodontal tissue. However, the relationship between periodontitis and miRNAs profile in circulation remains unclear. In this study, we investigated the effects of periodontitis on serum miRNAs profile in a rat model.
Material and Methods: Male Wistar rats (n=32, 8weeks old) were divided into four groups of eight rats each. The control groups received no treatment for 2 or 4weeks. In the other two groups, periodontitis was ligature induced for 2 or 4weeks. Serum miRNAs expression profiles of each group were compared.
Results: Ligation around teeth induced periodontal inflammation at 2weeks and periodontal tissue destruction at 4weeks. Microarray results showed that 25 miRNAs were expressed with a <0.5 or >2 difference between the control and periodontitis groups at 4weeks. Results of real-time PCR revealed that the periodontitis group up-regulated expression rates of serum miR-207 and miR-495 at 2weeks, and miR-376b-3p at 4weeks (p<0.05).
Conclusion: Serum miRNAs (miR-207, miR-495, and miR-376b-3p) could be valuable biomarkers for periodontitis.

DOI： 10.1111/jcpe.12536

MicroRNAs in Salivary Exosome as Potential Biomarkers of Aging. Reviewed International journal

Tatsuya Machida, Takaaki Tomofuji, Daisuke Ekuni, Takayuki Maruyama, Toshiki Yoneda, Yuya Kawabata, Hirofumi Mizuno, Hisataka Miyai, Muneyoshi Kunitomo, Manabu Morita

International journal of molecular sciences 16 ( 9 ) 21294 - 309 2015.9

Language：English Publishing type：Research paper (scientific journal) Publisher：MDPI AG

The aim of this study was to examine whether salivary exosomal miRNAs could be identified as aging biomarkers. Fifteen young healthy volunteers (median age, 21.0 years) and 13 old individuals (median age, 66.0 years) were recruited. Unstimulated whole saliva was collected, salivary exosomes were isolated, and total RNA was extracted. In a microarray, 242 miRNAs were commonly detected in these two mixed samples. Based on the cut-off values of 2- or 0.5-fold changes (FC) and regulatory power for aging process, six candidate miRNAs (miR-24-3p, miR-371a-5p, miR-3175, miR-3162-5p, miR-671-5p, and miR-4667-5p) were selected. After comparing each total RNA obtained by the 15 young and 13 old individuals to validate the FC values using quantitative real-time PCR, miR-24-3p was identified as a novel candidate aging biomarker. This pilot study suggested that salivary exosomal miRNAs could be identified as candidate aging biomarkers. To confirm whether miR-24-3p in salivary exosomes are suitable biomarkers of aging, further validation research is required.

DOI： 10.3390/ijms160921294

Drinking Hydrogen-Rich Water Has Additive Effects on Non-Surgical Periodontal Treatment of Improving Periodontitis: A Pilot Study. Reviewed International journal

Tetsuji Azuma, Mayu Yamane, Daisuke Ekuni, Yuya Kawabata, Kota Kataoka, Kenta Kasuyama, Takayuki Maruyama, Takaaki Tomofuji, Manabu Morita

Antioxidants (Basel, Switzerland) 4 ( 3 ) 513 - 22 2015.7

Language：English Publishing type：Research paper (scientific journal) Publisher：MDPI AG

Oxidative stress is involved in the pathogenesis of periodontitis. A reduction of oxidative stress by drinking hydrogen-rich water (HW) might be beneficial to periodontal health. In this pilot study, we compared the effects of non-surgical periodontal treatment with or without drinking HW on periodontitis. Thirteen patients (3 women, 10 men) with periodontitis were divided into two groups: The control group (n = 6) or the HW group (n = 7). In the HW group, participants consumed HW 4-5 times/day for eight weeks. At two to four weeks, all participants received non-surgical periodontal treatment. Oral examinations were performed at baseline, two, four and eight weeks, and serum was obtained at these time points to evaluate oxidative stress. At baseline, there were no significant differences in periodontal status between the control and HW groups. The HW group showed greater improvements in probing pocket depth and clinical attachment level than the control group at two, four and eight weeks (p < 0.05). The HW group also exhibited an increased serum level of total antioxidant capacity at four weeks, compared to baseline (p < 0.05). Drinking HW enhanced the effects of non-surgical periodontal treatment, thus improving periodontitis.

DOI： 10.3390/antiox4030513

Relationship between acetaldehyde concentration in mouth air and tongue coating volume Reviewed

Aya Yokoi, Takayuki Maruyama, Reiko Yamanaka, Daisuke Ekuni, Takaaki Tomofuji, Haruhiko Kashiwazaki, Yutaka Yamazaki, Manabu Morita

JOURNAL OF APPLIED ORAL SCIENCE 23 ( 1 ) 64 - 70 2015.1

Language：English Publishing type：Research paper (scientific journal) Publisher：UNIV SAO PAULO FAC ODONTOLOGIA BAURU

Objective: Acetaldehyde is the first metabolite of ethanol and is produced in the epithelium by mucosal ALDH, while higher levels are derived from microbial oxidation of ethanol by oral microflora such as Candida species. However, it is uncertain whether acetaldehyde concentration in human breath is related to oral condition or local production of acetaldehyde by oral microflora. The aim of this pilot study was to investigate the relationship between physiological acetaldehyde concentration and oral condition in healthy volunteers. Material and Methods: Sixty-five volunteers (51 males and 14 females, aged from 20 to 87 years old) participated in the present study. Acetaldehyde concentration in mouth air was measured using a portable monitor. Oral examination, detection of oral Candida species and assessment of alcohol sensitivity were performed. Results: Acetaldehyde concentration [median (25%, 75%)] in mouth air was 170.7 (73.5, 306.3) ppb. Acetaldehyde concentration in participants with a tongue coating status score of 3 was significantly higher than in those with a score of 1 (p<0.017). After removing tongue coating, acetaldehyde concentration decreased significantly (p<0.05). Acetaldehyde concentration was not correlated with other clinical parameters, presence of Candida species, smoking status or alcohol sensitivity. Conclusion: Physiological acetaldehyde concentration in mouth air was associated with tongue coating volume.

DOI： 10.1590/1678-775720140223

Serum Oxidative/anti-oxidative Stress Balance Is Dysregulated in Potentially Pulmonary Hypertensive Patients with Liver Cirrhosis: A Case Control Study. Reviewed

Masako Terao, Akinobu Takaki, Takayuki Maruyama, Hiroki Oe, Tetsuya Yasunaka, Naofumi Tamaki, Kazufumi Nakamura, Takaaki Tomofuji, Takahito Yagi, Hiroshi Sadamori, Yuzo Umeda, Susumu Shinoura, Ryuichi Yoshida, Kazuhiro Nouso, Daisuke Ekuni, Kazuko Koike, Fusao Ikeda, Hidenori Shiraha, Manabu Morita, Hiroshi Ito, Toshiyoshi Fujiwara, Kazuhide Yamamoto

Internal medicine (Tokyo, Japan) 54 ( 22 ) 2815 - 26 2015

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN SOC INTERNAL MEDICINE

Objective Hepatopulmonary syndrome (HPS) is characterized by vascular dilatation and hyperdynamic circulation, while portopulmonary hypertension (POPH) is characterized by vasoconstriction with fibrous obliteration of the vascular bed. Vasoactive molecules such as nitric oxide (NO) are candidate factors for cirrhotic complications associated with these diseases. However, oxidative stress balance is not well characterized in HPS and POPH. The present objective is to investigate the oxidative stress and anti-oxidative stress balance and NO pathway balance in patients with potential HPS and POPH.
Methods We recruited patients with decompensated cirrhosis (n = 69) admitted to our hospital as liver transplantation candidates. Patients exhibiting partial pressure of oxygen lower than 80 mmHg and alveolararterial oxygen gradient (AaDO(2)) >= 15 mmHg were categorized as potentially having HPS (23 of 69 patients). Patients exhibiting a tricuspid regurgitation pressure gradient >= 25 mmHg were categorized as potentially having POPH (29 of 61 patients). Serum reactive oxygen metabolites were measured and anti-oxidative OXY-adsorbent test (OXY) were performed, and the balance of these tests was defined as the oxidative index. The correlation between these values and the clinical characteristics of the patients were assessed in a cross-sectional study.
Results Potential HPS patients exhibited no correlation with oxidative stress markers. Potential POPH patients exhibited lower OXY (p = 0.037) and higher oxidative index values (p = 0.001). Additionally, the vascular NO synthase enzyme inhibiting protein, asymmetric dimethylarginine, was higher in potential POPH patients (p = 0.049). The potential POPH patients exhibited elevated AaDO(2), suggesting the presence of pulmonary shunting.
Conclusion Potential POPH patients exhibited elevated oxidative stress with decreased anti-oxidative function accompanied by inhibited NO production. Anti-oxidants represent a candidate treatment for potential POPH patients.

DOI： 10.2169/internalmedicine.54.4889

Severe periodontitis is inversely associated with coffee consumption in the maintenance phase of periodontal treatment. Reviewed International journal

Tatsuya Machida, Takaaki Tomofuji, Daisuke Ekuni, Tetsuji Azuma, Noriko Takeuchi, Takayuki Maruyama, Shinsuke Mizutani, Kota Kataoka, Yuya Kawabata, Manabu Morita

Nutrients 6 ( 10 ) 4476 - 90 2014.10

Language：English Publishing type：Research paper (scientific journal) Publisher：MDPI AG

This cross-sectional study addressed the relationship between coffee consumption and periodontitis in patients during the maintenance phase of periodontal treatment. A total of 414 periodontitis patients in the maintenance phase of periodontal treatment completed a questionnaire including items related to coffee intake and underwent periodontal examination. Logistic regression analysis showed that presence of moderate/severe periodontitis was correlated with presence of hypertension (Odds Ratio (OR) = 1.99, p < 0.05), smoking (former, OR = 5.63, p < 0.01; current, OR = 6.81, p = 0.076), number of teeth present (OR = 0.89, p < 0.001), plaque control record >= 20% (OR = 1.88, p < 0.05), and duration of maintenance phase (OR = 1.07, p < 0.01). On the other hand, presence of severe periodontitis was correlated with smoking (former, OR = 1.35, p = 0.501; current, OR = 3.98, p < 0.05), coffee consumption (>= 1 cup/day, OR = 0.55, p < 0.05), number of teeth present (OR = 0.95, p < 0.05), and bleeding on probing >= 20% (OR = 3.67, p < 0.001). There appears to be an inverse association between coffee consumption (>= 1 cup/day) and prevalence of severe periodontitis in the maintenance phase of periodontal treatment.

DOI： 10.3390/nu6104476

アルコール摂取後のブラッシング行動と歯周病の活動性との関連

水谷慎介, 江國大輔, 友藤孝明, 山根真由, 東哲司, 丸山貴之, 町田達哉, 米田俊樹, 片岡広太, 佐久本雅美, 川端勇也, 大森智栄, 森田学

口腔衛生学会雑誌 64 ( 2 ) 173 - 173 2014.4

Occlusion and Weight Change in a Patient After Esophagectomy: Success Derived from Restoration of Occlusal Support Reviewed

Reiko Yamanaka, Yoshihiko Soga, Mami Minakuchi, Kumiko Nawachi, Takayuki Maruyama, Takuo Kuboki, Manabu Morita

INTERNATIONAL JOURNAL OF PROSTHODONTICS 26 ( 6 ) 574 - 576 2013.11

Language：English Publishing type：Research paper (scientific journal) Publisher：QUINTESSENCE PUBLISHING CO INC

Occlusal support may be an important factor affecting nutritional support after major surgery. This report presents a patient who gained body weight after receiving a new prosthesis. The patient was an 82-year-old man with thoracic esophageal carcinoma. He did not have occlusal support because of multiple caries lesions. His body weight slowly increased after surgery, but almost stopped in the period of 54 to 68 days after surgery. After treatment with dentures (day 72 postsurgery), body weight gain was observed again, although his medical treatment had not changed. An appropriate prosthesis could contribute to perioperative nutrition support and may lead to earlier recovery after surgery.

DOI： 10.11607/ijp.3622

Serum oxidative-anti-oxidative stress balance is dysregulated in patients with hepatitis C virus-related hepatocellular carcinoma. Reviewed International journal

Mamoru Nishimura, Akinobu Takaki, Naofumi Tamaki, Takayuki Maruyama, Hideki Onishi, Sayo Kobayashi, Kazuhiro Nouso, Tetsuya Yasunaka, Kazuko Koike, Hiroaki Hagihara, Kenji Kuwaki, Shinichiro Nakamura, Fusao Ikeda, Yoshiaki Iwasaki, Takaaki Tomofuji, Manabu Morita, Kazuhide Yamamoto

Hepatology research : the official journal of the Japan Society of Hepatology 43 ( 10 ) 1078 - 92 2013.10

Language：English Publishing type：Research paper (scientific journal)

Aim: Oxidative stress is associated with progression of chronic liver disease (CLD). This association is best established in chronic hepatitis C. However, the anti-oxidative state is not well characterized. The objective of the present study was to investigate the balance of oxidative and anti-oxidative stress in CLD patients. Methods: We recruited a study population of 208 patients, including healthy volunteers (HV
n=15), patients with hepatitis B virus (HBV)-related CLD without or with hepatocellular carcinoma (HBV-non-HCC, n=25, and HBV-HCC, n=50, respectively), and patients with hepatitis C virus (HCV)-related CLD without or with HCC (HCV-non-HCC, n=49, and HCV-HCC, n=69, respectively). Serum levels of reactive oxygen metabolites (ROM) and anti-oxidative markers (OXY-adsorbent test
OXY) were determined, and the balance of these values was used as the oxidative index. Correlations among ROM, OXY, oxidative index and clinical characteristics were investigated. Results: Patients with CLD exhibited elevated ROM and oxidative index compared to HV. Among patients with CLD, HCV positive status correlated with increased ROM. In CLD, HCV-HCC patients exhibited the highest ROM levels. Among HCV-related CLD patients, lower OXY correlated with HCC positive status, but was recovered by eradication of HCC. In HCV-HCC, lower OXY correlated with high PT-INR. Conclusion: HCV positive CLD patients displayed higher oxidative stress and HCV-HCC patients displayed lower anti-oxidative state. Anti-oxidative state depression was associated with liver reservoir-related data in HCV-HCC and could be reversed with HCC eradication. © 2012 The Japan Society of Hepatology.

DOI： 10.1111/hepr.12048

Relationship between serum albumin concentration and periodontal condition in patients with head and neck cancer. Reviewed International journal

Takayuki Maruyama, Reiko Yamanaka, Aya Yokoi, Daisuke Ekuni, Takaaki Tomofuji, Nobuyoshi Mizukawa, Tomoo Onoda, Motoharu Eguchi, Manabu Morita

Journal of periodontology 83 ( 9 ) 1110 - 5 2012.9

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：AMER ACAD PERIODONTOLOGY

Background: Serum albumin concentration is known to be an independent predictor of survival in head and neck cancer. The previous studies suggested relationships between serum albumin concentration and oral health status in populations without serious systemic disorders. However, these relationships remain unclear in patients with head and neck cancer. The purpose of this study is to investigate the relationship between serum albumin concentration and oral health status in patients with head and neck cancer.
Methods: Fifty individuals diagnosed with primary head and neck cancer, 25 individuals with normal serum albumin concentration (>= 3.85 g/dL), and 25 age- and sex-matched individuals with lower serum albumin concentration (<3.85 g/dL) were analyzed. General status, including cancer stage, body mass index, drinking and smoking habits, and biochemical serum markers, were evaluated. Oral health status, including periodontal condition and occlusion tooth pairs, were also evaluated.
Results: Mean clinical attachment level (CAL) and C-reactive protein in the lower serum albumin concentration group were greater than those in the normal serum albumin concentration group (P = 0.009 and P = 0.002, respectively). However, there were no significant differences in any other oral and/or serum parameters between the two serum albumin groups. A logistic regression model showed that mean CAL was significantly associated with high or low levels of serum albumin concentration (odds ratio = 9.752; 95% confidence interval = 1.702 to 55.861; P = 0.011).
Conclusions: This study suggests an association between periodontal disease and serum albumin concentration in patients with head and neck cancer. Longitudinal studies are necessary to examine the causal relationship between serum albumin concentration and periodontal condition. J Periodontol 2012;83:1110-1115.

DOI： 10.1902/jop.2011.110536

Relationships between periodontal inflammation, lipid peroxide and oxidative damage of multiple organs in rats. Reviewed

Takaaki Tomofuji, Daisuke Ekuni, Koichiro Irie, Tetsuji Azuma, Naofumi Tamaki, Takayuki Maruyama, Tatsuo Yamamoto, Tatsuo Watanabe, Manabu Morita

Biomedical research (Tokyo, Japan) 32 ( 5 ) 343 - 9 2011.10

Language：English Publishing type：Research paper (scientific journal) Publisher：BIOMEDICAL RESEARCH PRESS LTD

Gingival response to periodontal inflammation generates excessive lipid peroxide and such a condition may augment systemic health through increased circulating lipid peroxide. The purpose of the present study was to investigate whether the generation of lipid peroxide in periodontal inflammation could induce tissue injury in the liver, heart, kidney and brain using a rat model. Twelve Wistar rats (8 week-old male) were divided into 2 groups: the periodontal inflammation group, receiving topical application of lipopolysaccharide and proteases to the gingival sulcus for 4 weeks, and the control group using instead pyrogen-free water. After blood samples were collected, specimens from the brain, heart, liver and kidney were resected to determine the concentration of 8-hydroxydeoxyguanosine (an indicator of oxidative DNA damage). Gingival and serum levels for hexanoyl-lysine were measured to evaluate lipid peroxide. Administration of lipopolysaccharide and proteases induced periodontal inflammation, with increasing gingival and serum levels of hexanoyl-lysine. The level of 8-hydroxydeoxyguanosine increased 2.27, 2.01, 1.49 and 1.40 times in mitochondrial DNA from the liver, heart, kidney and brain of rats with periodontal inflammation, respectively. The results reveal that excessive production of lipid peroxide following periodontal inflammation is involved in oxidative DNA damage of the brain, heart, liver and kidney.

Supplementation of green tea catechins in dentifrices suppresses gingival oxidative stress and periodontal inflammation. Reviewed International journal

Takayuki Maruyama, Takaaki Tomofuji, Yasumasa Endo, Koichiro Irie, Tetsuji Azuma, Daisuke Ekuni, Naofumi Tamaki, Tatsuo Yamamoto, Manabu Morita

Archives of oral biology 56 ( 1 ) 48 - 53 2011.1

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：PERGAMON-ELSEVIER SCIENCE LTD

Objective: This study examined the effects of a dentifrice containing green tea catechins on gingival oxidative stress and periodontal inflammation using a rat model.
Design: Twenty-four male Wister rats were randomly divided into four groups. The first group (Control group) received no treatment for 8 weeks. Periodontal inflammation was induced in the second group for 8 weeks. Periodontal inflammation was induced in the last two groups for 8 weeks and dentifrices with or without green tea catechins were topically applied to the gingival sulcus daily for 4 weeks prior to the end of the experimental period. Results: Rats that had experimental periodontal inflammation showed apical migration of the junctional epithelium, alveolar bone loss and inflammatory cell infiltration in the connective tissue subjacent to the junctional epithelium at 8 weeks, whilst the control group showed no pathologic changes. Topical application of a green tea catechin-containing dentifrice reduced inflammatory cell infiltration in the periodontal lesions to a greater degree than the control dentifrice at 8 weeks. The gingiva in which green tea catechin-containing dentifrice was applied also showed a lower level of expression of hexanoyl-lysine (a marker of lipid peroxidation), nitrotyrosine (a marker of oxidative protein damage), and tumour necrosis factor-a (an indicator of pro-inflammatory cytokines) at 8 weeks compared to gingiva in which the control dentifrice was applied.
Conclusions: Adding green tea catechins to a dentifrice may contribute to prevention of periodontal inflammation by decreasing gingival oxidative stress and expression of pro-inflammatory cytokines. (C) 2010 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.archoralbio.2010.08.015

Effects of improvement in periodontal inflammation by toothbrushing on serum lipopolysaccharide concentration and liver injury in rats. Reviewed International journal

Takaaki Tomofuji, Daisuke Ekuni, Toshihiro Sanbe, Tetsuji Azuma, Naofumi Tamaki, Koichiro Irie, Takayuki Maruyama, Tatsuo Yamamoto, Tatsuo Watanabe, Mutsumi Miyauchi, Takashi Takata

Acta odontologica Scandinavica 67 ( 4 ) 200 - 5 2009.7

Language：English Publishing type：Research paper (scientific journal) Publisher：TAYLOR & FRANCIS LTD

Objective. Periodontitis increases the serum lipopolysaccharide level, contributing to liver injury. Toothbrushing improves periodontitis and may also affect serum lipopolysaccharide concentration and periodontitis-induced liver injury. The purpose of the present study was to examine whether the improvement in periodontal inflammation by toothbrushing clinically affects the serum lipopolysaccharide level and hepatic pathological changes in rat periodontitis. Material and methods. Thirty male Wistar rats were divided into 5 groups, 2 groups receiving topical application of pyrogen-free water to the gingival sulcus for 4 or 8 weeks. The next 2 groups received topical application of lipopolysaccharide and proteases for 4 or 8 weeks. The last group received topical application of lipopolysaccharide and proteases for 8 weeks, and the palatal gingiva was brushed with a powered toothbrush once a day for 4 weeks prior to the end of the experimental period. Results. Topical application of lipopolysaccharide and proteases induced not only periodontal inflammation but also an elevation in the serum lipopolysaccharide concentration, with increasing hepatic inflammation, steatosis and 8-hydroxydeoxyguanosine levels in a time-dependent mariner. The rats that received gingival stimulation showed decreased polymorphonuclear leukocyte infiltration and collagen loss levels in the periodontal lesions. Furthermore, this group also showed a decrease in serum lipopolysaccharide concentration and hepatic inflammation, steatosis and 8-hydroxydeoxyguanosine levels, compared with the group receiving no treatment. Conclusions. Toothbrushing promoted healing of periodontal lesions, decreased serum lipopolysaccharide concentration and suppressed liver injury in a rat periodontitis model.

DOI： 10.1080/00016350902794818

Vitamin C intake attenuates the degree of experimental atherosclerosis induced by periodontitis in the rat by decreasing oxidative stress. Reviewed International journal

Daisuke Ekuni, Takaaki Tomofuji, Toshihiro Sanbe, Koichiro Irie, Tetsuji Azuma, Takayuki Maruyama, Naofumi Tamaki, Jun Murakami, Susumu Kokeguchi, Tatsuo Yamamoto

Archives of oral biology 54 ( 5 ) 495 - 502 2009.5

Language：English Publishing type：Research paper (scientific journal) Publisher：PERGAMON-ELSEVIER SCIENCE LTD

Objective: Periodontitis has been causally linked to cardiovascular disease, which is mediated through the oxidative stress induced by periodontitis. Since vitamin C has been suggested to limit oxidative damage, we hypothesized that vitamin C intake may reduce endothelial oxidative stress induced by periodontitis in the aorta. The aim of this study was to investigate the effects of vitamin C intake on the initiation of atherosclerosis in a ligature-induced rat periodontitis model.
Design: Eighteen 8-week-old-male Wistar rats were divided into three groups of six rats and all rats received daily fresh water and powdered food through out the 6-week study. In the vitamin C and periodontitis groups, periodontitis was ligature-induced for the first 4 weeks. In the vitamin C group, rats were given distilled water containing 1 g/L vitamin C for the 2 weeks after removing the ligature.
Results: In the periodontitis group, there was lipid deposition in the descending aorta and significant increases of serum level of hexanoyl-lysine (HEL), and aortic levels of nitrotyrosine expression, HEL expression and 8-hydroxydeoxyguanosine (8-OHdG) compared to the control group. Vitamin C intake significantly increased plasma vitamin C level and GSH:GSSG ratio (178% and 123%, respectively), and decreased level of serum HEL and aortic levels of nitrotyrosine, HEL and 8-OHdG (23%, 87%, 84%, and 38%, respectively).
Conclusions: These results suggest that vitamin C intake attenuates the degree of experimental atherosclerosis induced by periodontitis in the rat by decreasing oxidative stress. (C) 2009 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.archoralbio.2009.02.006

Validity of a questionnaire for periodontitis screening of Japanese employees. Reviewed International journal

Tatsuo Yamamoto, Reiko Koyama, Naofumi Tamaki, Takayuki Maruyama, Takaaki Tomofuji, Daisuke Ekuni, Reiko Yamanaka, Tetsuji Azuma, Manabu Morita

Journal of occupational health 51 ( 2 ) 137 - 43 2009.3

Language：English Publishing type：Research paper (scientific journal) Publisher：JAPAN SOC OCCUPATIONAL HEALTH

Validity of a Questionnaire for Periodontitis Screening of Japanese Employees: Tatsuo YAMAMOTO, et al. Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences-Objectives: Workplaces are suitable for screening for periodontal disease effectively. However, the majority of workplaces do not have a screening program. One possible reason may be that pocket probing, which is commonly used for the screening, needs qualified examiners and is time-consuming. In this study, the validity of a self-reported questionnaire was assessed for screening of periodontitis in 50- to 59-yr-old male employees in Japan. Methods: A total of 250 people were asked to complete a self-administered questionnaire regarding signs and symptoms of periodontal disease, and experience of periodontal treatment, followed by a clinical examination by a dentist. Subjects with at least one tooth having a clinical attachment loss of 7 mm or more were defined as periodontitis patients. Results: Thirteen percent of the subjects were diagnosed as having periodontitis. Logistic regression selected 4 questions, "Are you a current or past smoker?", "Have your gums bled recently?", "Do you think that you can see more roots of teeth than in the past?", and "Have you ever been told that you need periodontal or gum treatment?" as potential predictors of periodontitis. When subjects with at least 3 "yes" responses to the 4 questions were separated from the others, the subjects with periodontitis were separated most effectively (showing the highest sensitivity + specificity: 1.524) from those without. The area under the receiver operating characteristic curve was 0.81. Conclusions: These results suggest that the self-reported questions are useful for screening of periodontitis in 50- to 59-yr-old Japanese workers.

DOI： 10.1539/joh.l8108

Effects of vitamin C intake on gingival oxidative stress in rat periodontitis. Reviewed International journal

Takaaki Tomofuji, Daisuke Ekuni, Toshihiro Sanbe, Koichiro Irie, Tetsuji Azuma, Takayuki Maruyama, Naofumi Tamaki, Jun Murakami, Susumu Kokeguchi, Tatsuo Yamamoto

Free radical biology & medicine 46 ( 2 ) 163 - 8 2009.1

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

Increased levels of oxidative stress due to excessive production of reactive oxygen species are involved in the pathogenesis of periodontitis. Studies Suggest a negative association between plasma vitamin C level and the severity of periodontitis. We hypothesized that increases in plasma vitamin C levels after vitamin C intake might clinically reduce gingival oxidative stress in a rat periodontitis model. A ligature was placed around rat mandibular molars for 4 weeks to induce periodontitis, and the rats were then given drinking water with or without 1 g/L vitamin C for 2 weeks after the ligature was removed. The periodontitis-induced rats showed a 149% increase in 8-hydroxydeoxyguanosine level and a 40% decrease in reduced:oxidized glutathione ratio in gingival tissue. Vitamin C intake induced a 175% increase in plasma vitamin C level, resulting in an improvement in the gingival 8-hydroxydeoxyguanosine level (decreased) and in the reduced:oxidized glutathione ratio (increased). Furthermore, in ligature-induced periodontitis lesions, gene expression encoding inflammation, including interleukin-1 alpha and interleukin-1 beta, was more than twofold down-regulated by vitamin C intake. The results suggest that systemic administration of vitamin C could be clinically beneficial in improving periodontitis-induced oxidative stress by down-regulating inflammatory gene expression. (C) 2008 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.freeradbiomed.2008.09.040

Oxidative damage of rat liver induced by ligature-induced periodontitis and chronic ethanol consumption. Reviewed International journal

Takaaki Tomofuji, Toshihiro Sanbe, Daisuke Ekuni, Tetsuji Azuma, Koichiro Irie, Takayuki Maruyama, Naofumi Tamaki, Tatsuo Yamamoto

Archives of oral biology 53 ( 12 ) 1113 - 8 2008.12

Language：English Publishing type：Research paper (scientific journal) Publisher：PERGAMON-ELSEVIER SCIENCE LTD

Objective: oxidative stress plays a central role in the initiation and progression of liver disease. Chronic ethanol consumption induces oxidative damage of the liver. Using a rat model, we previously showed that chronic administration of lipopolysaccharide and proteases to gingival sulcus induced both periodontal inflammation and liver injury. Periodontitis and ethanol consumption may have an additional effect on hepatic oxidative damage. The present study investigated the effects of periodontitis on ethanol-induced oxidative damage of the liver using a rat model.
Design: Male Wistar rats were divided into four groups (six rats/group). During the experimental period of eight weeks, two groups were fed an ethanol-containing liquid diet, and two groups were on a pair-fed control diet. Four weeks prior to the end of the experimental period, one group from each dietary treatment was ligated to induce periodontitis, while the other group was left unligated. In order to evaluate hepatic oxidative damage, the level of hexanoyl-lysine and the ratio of reduced form glutathione/oxidized form glutathione (GSH/GSSG) was determined. The concentration of blood hexanoyl-lysine was also measured as an index of circulating lipid peroxide.
Results: Ligature-induced periodontitis increased plasma levels of hexanoyl-lysine. in the liver, periodontitis decreased the CSH/GSSG ratio, and the combination of periodontitis and ethanol consumption induced a significant increase in hexanoyl-lysine level compared to ethanol consumption alone.
Conclusion: In the rat model, ligature-induced periodontitis increased plasma lipid peroxide, decreased the hepatic GSH/GSSG ratio and augmented ethanol-induced lipid peroxidation in the liver. (C) 2008 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.archoralbio.2008.05.015

Relationship between periodontal condition and plasma reactive oxygen metabolites in patients in the maintenance phase of periodontal treatment. Reviewed International journal

Naofumi Tamaki, Takaaki Tomofuji, Takayuki Maruyama, Daisuke Ekuni, Reiko Yamanaka, Noriko Takeuchi, Tatsuo Yamamoto

Journal of periodontology 79 ( 11 ) 2136 - 42 2008.11

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER ACAD PERIODONTOLOGY

Background: The relationship between systemic antioxidative status and periodontal condition has been investigated in epidemiologic studies. However, little literature is available with regard to the correlation between systemic reactive oxygen species and periodontal condition. The purpose of this cross-sectional study was to investigate the relationship between plasma reactive oxygen metabolites (ROM) and periodontal condition in patients in the maintenance phase of periodontal treatment.
Methods: Eighty-one subjects (mean age: 57.4 years) who had entered a periodontal maintenance program were examined for probing depth (PD) and clinical attachment level (CAL). Plasma levels of ROM and biologic antioxidant potential (BAP) were determined with a free radical electric evaluator.
Results: The plasma level of ROM was positively correlated to mean CAL (r = 0.281; P = 0.011) and percentage of teeth with CAL A mm (r = 0.236; P = 0.034), but not mean PD (r = 0.196; P = 0.080). Logistic regression analysis showed that subjects with ROM levels >400 Carratelli units (CARR U) had significantly higher mean CAL compared to subjects with ROM >400 CARR U after adjusting for age, gender, and the number of teeth present (P = 0.011). However, the plasma level of BAP was not significantly correlated with the periodontal parameters.
Conclusions: A positive association was found between plasma oxidative status and CAL in patients in the maintenance phase of periodontal therapy. A systemic increase in oxidative stress may influence the rate of progression of periodontal disease. J Periodontol 2008; 79:2136-2142.

DOI： 10.1902/jop.2008.080082

Effects of Ethanol Consumption on Periodontal Inflammation in Rats Reviewed

K. Irie, T. Tomofuji, N. Tamaki, T. Sanbe, D. Ekuni, T. Azuma, T. Maruyama, T. Yamamoto

Journal of Dental Research 87 ( 5 ) 456 - 460 2008.5

Relationship between periodontal status and levels of oxidative stress and antioxidant potential in plasma

Maruyama Takayuki, Tamaki Naofumi, Tomofuji Takaaki, Ekuni Daisuke, Yamanaka Reiko, Takeuchi Noriko, Yamamoto Tatsuo

Program and Abstracts of Annual Meeting of the Japanese Society of Periodontology 2008 52 - 52 2008

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