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Nagy TL, Mikecs B, Lohinai ZM, Vág J. Dose-related effect of acetylcholine on human gingival blood flow. BMC Oral Health 2024; 24:1398. [PMID: 39551739 PMCID: PMC11571918 DOI: 10.1186/s12903-024-05169-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2024] [Accepted: 11/07/2024] [Indexed: 11/19/2024] Open
Abstract
BACKGROUND This study investigates the dose-response relationship of acetylcholine (ACh) on healthy human gingival blood flow (GBF). Understanding this dose-response relationship contributes to studying vasodilatory mechanisms in various pathological conditions. METHODS The study involved 22 young healthy men (21 - 32 years) to investigate the dose-response relationship of ACh on GBF. Semi-circular wells were created on the labial surface of the upper right second incisor (FDI #12) and upper left first incisor (FDI #21), including the gingival sulcus, for the application of drugs. ACh-chloride solutions at 0.1, 1, and 10 mg/mL were administered to the gingival sulcus of tooth FDI #12 with a Hamilton syringe. Physiological saline was applied on the contralateral side to FDI #21 as a control. The GBF was measured non-invasively by the laser speckle contrast imaging method in four 1mm high adjacent regions: coronal, midway1, midway2, and apical, and was expressed in a laser speckle perfusion unit (LSPU). After the baseline blood flow recording, ACh doses were applied sequentially, with washout periods in between. Data were statistically analyzed using a linear mixed model. RESULTS The GBF did not change on the saline site throughout the experiment. The GBF was significantly higher at the coronal region after all ACh doses (baseline: 218±31 LSPU, and 227±38 LSPU p < 0.05, 239±40 LSPU p < 0.001, 291±54 LSPU p < 0.001, respectively) compared to the saline. It was also elevated following 1 and 10 mg/mL at the midway1 (245±48 LSPU, p < 0.05, 293±65 LSPU p < 0.001). At midway2 and apical, only the 10 mg/mL dose was effective (285±71 LSPU, p < 0.001; 302±82 LSPU, p < 0.001). CONCLUSIONS Our findings suggest a dose-dependent vasodilation to ACh, emphasizing its role in human gingival microcirculation. Only the 10 mg/mL ACh could evoke remote vasodilation 3 mm from the application. The described method could facilitate the investigation of endothelium-dependent vasodilation in disorders affecting microcirculation, such as periodontitis or diabetes.
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Affiliation(s)
- Tamás László Nagy
- Department of Restorative Dentistry and Endodontics, Faculty of Dentistry, Semmelweis University, H-1088 Budapest, Szentkirályi utca 47, Budapest, Hungary
| | - Barbara Mikecs
- Department of Restorative Dentistry and Endodontics, Faculty of Dentistry, Semmelweis University, H-1088 Budapest, Szentkirályi utca 47, Budapest, Hungary
| | - Zsolt M Lohinai
- Department of Restorative Dentistry and Endodontics, Faculty of Dentistry, Semmelweis University, H-1088 Budapest, Szentkirályi utca 47, Budapest, Hungary
| | - János Vág
- Department of Restorative Dentistry and Endodontics, Faculty of Dentistry, Semmelweis University, H-1088 Budapest, Szentkirályi utca 47, Budapest, Hungary.
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Surlari Z, Ciurcanu OE, Budala DG, Butnaru O, Luchian I. An Update on the Interdisciplinary Dental Care Approach for Geriatric Diabetic Patients. Geriatrics (Basel) 2023; 8:114. [PMID: 38132485 PMCID: PMC10743251 DOI: 10.3390/geriatrics8060114] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 11/14/2023] [Accepted: 11/23/2023] [Indexed: 12/23/2023] Open
Abstract
Diabetes mellitus is a prevalent health issue escalating worldwide that gives rise to numerous problems. Periodontal disorders are recognized as the sixth consequence associated with diabetes mellitus. Research shows that dental health affects overall health, and this knowledge is changing the dental field. The correct choice of glucose goal levels and the optimal selection of glucose-lowering medications are determined by a comprehensive geriatric assessment, an estimate of life expectancy, and a rationale for therapy at regular intervals in elderly diabetics. This article provides an overview of the correlation between diabetes and oral health, with a specific emphasis on xerostomia, periodontal disease, and dental caries. Thus, dentists play a significant role within the allied health profession by contributing to the provision of oral care for those diagnosed with diabetes, with a special focus on geriatric patients.
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Affiliation(s)
- Zenovia Surlari
- Department of Fixed Prosthodontics, Faculty of Dental Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 16 Universității Street, 700115 Iasi, Romania;
| | - Oana Elena Ciurcanu
- Department of Dental Surgery, Grigore T. Popa University of Medicine and Pharmacy, Universitatii Street 16, 700115 Iasi, Romania;
| | - Dana Gabriela Budala
- Department of Implantology, Removable Prostheses, Dental Prostheses Technology, “Grigore T. Popa” University of Medicine and Pharmacy, 16 Universitătii Street, 700115 Iasi, Romania
| | - Oana Butnaru
- Department of Biophysics, Faculty of Dental Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, Romania;
| | - Ionut Luchian
- Department of Periodontology, Grigore T. Popa University of Medicine and Pharmacy, Universitatii Street 16, 700115 Iasi, Romania
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Chang YR, Cheng WC, Hsiao YC, Su GW, Lin SJ, Wei YS, Chou HC, Lin HP, Lin GY, Chan HL. Links between oral microbiome and insulin resistance: Involvement of MAP kinase signaling pathway. Biochimie 2023; 214:134-144. [PMID: 37442534 DOI: 10.1016/j.biochi.2023.06.013] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Revised: 06/29/2023] [Accepted: 06/30/2023] [Indexed: 07/15/2023]
Abstract
Oral dysbiosis contributes to periodontitis and has implications for systemic diseases. Diabetes mellitus is a common metabolic disorder characterized by impaired glucose regulation. AMP-activated protein kinase (AMPK) plays a vital role in regulating glucose uptake and glycogenesis in the liver. This study aimed to investigate the association between periodontal bacteria and diabetes mellitus. A clinical trial was conducted to explore the association between oral bacteria and hyperglycemia. Additionally, we elucidated the molecular mechanisms by which periodontal bacteria cause insulin resistance. In the clinical trial, we discovered significant alterations in the expression levels of Fusobacterium nucleatum (Fn) and Tannerella forsythia (Tf) in patients with diabetes compared with healthy controls. Furthermore, Fn and Tf levels positively correlated with fasting blood glucose and glycated hemoglobin (HbA1C) levels. Moreover, we explored and elucidated the molecular mechanism by which Fusobacterium nucleatum culture filtrate (FNCF) induces cytokine release via the Toll-like receptor 2 (TLR2) signaling pathway in human gingival epithelial Smulow-Glickman (S-G) cells. This study investigated the effects of cytokines on insulin resistance pathways in liver cells. The use of an extracellular signal-regulated kinase (ERK) inhibitor (U0126) demonstrated that FNCF regulates the insulin receptor substrate 1 and protein kinase B (IRS1/AKT) signaling pathway, which affects key proteins involved in hepatic glycogen synthesis, including glycogen synthase kinase-3 beta (GSK3β) and glycogen synthase (GS), ultimately leading to insulin resistance. These findings suggest that ERK plays a crucial role in hepatocyte insulin resistance.
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Affiliation(s)
- Yi-Ru Chang
- Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan; General Biologicals Corporation, Hsinchu, Taiwan
| | - Wen-Chi Cheng
- SDGs Teaching and Research Headquarters, Tzu Chi University, Hualien, Taiwan
| | - Ya-Chun Hsiao
- Department of Endocrinology and Metabolism, Hsinchu Mackay Memorial Hospital, Hsinchu, Taiwan
| | - Guan-Wei Su
- Dental Department of Hsinchu Mackay Memorial Hospital, Hsinchu, Taiwan
| | - Shan-Jen Lin
- Dental Department of Hsinchu Mackay Memorial Hospital, Hsinchu, Taiwan
| | - Yu-Shan Wei
- Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan
| | - Hsiu-Chuan Chou
- Institute of Analytical and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan
| | | | - Guan-Yu Lin
- Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan
| | - Hong-Lin Chan
- Department of Medical Science and Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu, Taiwan.
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4
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Exploring the Mechanisms and Association between Oral Microflora and Systemic Diseases. Diagnostics (Basel) 2022; 12:diagnostics12112800. [PMID: 36428859 PMCID: PMC9689323 DOI: 10.3390/diagnostics12112800] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Revised: 10/01/2022] [Accepted: 10/12/2022] [Indexed: 11/18/2022] Open
Abstract
The scope of dentistry is ever-changing and dynamic in all fields of dentistry including periodontal health and disease. Recent studies show that oral health and systemic health are interdependent, particularly in the way that poor oral hygiene and periodontal health affect the systemic health of an individual and vice versa. Periodontal diseases are multifactorial in nature in which the role of bacterial infections is inevitable. Furthermore, high-throughput sequencing technologies have shed light on the dysregulation of the growth of oral microbial flora and their environment, including those that are associated with periodontitis and other oral and non-oral diseases. Under such circumstances, it becomes important to explore oral microbiota and understand the effects of periodontal pathogens in the pathogenesis of systemic diseases. In addition, it may strengthen our view that a better understanding of oral microbial flora and proper examination of the oral cavity may aid in the early diagnosis and possible treatment of systemic diseases and conditions. This will eventually lead to providing better care to our patients. Therefore, in this research, we attempt to outline the periodontal pathophysiology along with the role of periodontal pathogens in some commonly encountered systemic conditions.
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5
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Vág J, Nagy TL, Mikecs B. Sex-related differences in endothelium-dependent vasodilation of human gingiva. BMC Oral Health 2022; 22:177. [PMID: 35562729 PMCID: PMC9107103 DOI: 10.1186/s12903-022-02186-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2021] [Accepted: 04/14/2022] [Indexed: 11/10/2022] Open
Abstract
Background Sex hormones influence circulation, periodontitis, and wound healing. The aim of the study was to compare the endothelium-dependent and independent vasodilation in human gingiva in men and women. Methods Gingival blood flow was evaluated in twelve male and twelve female subjects with healthy gingiva and no systemic conditions after acetylcholine or nitric oxide donor (NitroPOHL). Agonists were administered into the gingival sulcus at the right secondary incisor (test site). Regional gingival blood flow (GBF) was imaged by Laser Speckle Contrast Imager from the marginal gingiva to the mucogingival junction in four consecutive regions (coronal, midway1, midway2 and apical). Blood flow was expressed in Laser Speckle Perfusion Unit (LSPU). The absolute maximal blood flow change (Dmax), the area under the blood flow curve (AUC), and the time to peak (TTP) were calculated.
Results Males had higher baseline GBF than females (257 ± 18.2 vs. 225 ± 18.8 LSPU, p < 0.001). Acetylcholine and NitroPOHL significantly increased the GBF in all test regions. The Dmax after the acetylcholine was reduced apically compared to the coronal (90 ± 13 LSPU vs. 117 ± 7 LSPU, p < 0.01), but it was similar after NitroPOHL (78 ± 9 LSPU vs. 86 ± 6 LSPU, p = 0.398) in both sexes. The Dmax and AUC were higher, and the TTP was smaller in men in most regions after acetylcholine but not after NitroPOHL. Conclusion In the human gingiva, the endothelium-independent vasodilation propagates without attenuation in the line of the vascular supply in both sexes. At the same time, the endothelium-dependent ascending vasodilation attenuates similarly in men and women. However, men had more pronounced endothelium-dependent vasodilation than women. Therefore, it might contribute to the increased severity of periodontal disease in men. Trial registration The study was registered with ClinicalTrials.gov on 09.06.2021 (NCT04918563).
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Affiliation(s)
- János Vág
- Department of Conservative Dentistry, Faculty of Dentistry, Semmelweis University, Szentkirályi utca 47, Budapest, 1088, Hungary.
| | - Tamás László Nagy
- Department of Conservative Dentistry, Faculty of Dentistry, Semmelweis University, Szentkirályi utca 47, Budapest, 1088, Hungary
| | - Barbara Mikecs
- Department of Conservative Dentistry, Faculty of Dentistry, Semmelweis University, Szentkirályi utca 47, Budapest, 1088, Hungary
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Celik D, Kantarci A. Vascular Changes and Hypoxia in Periodontal Disease as a Link to Systemic Complications. Pathogens 2021; 10:1280. [PMID: 34684229 PMCID: PMC8541389 DOI: 10.3390/pathogens10101280] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Revised: 09/27/2021] [Accepted: 10/02/2021] [Indexed: 12/13/2022] Open
Abstract
The hypoxic microenvironment caused by oral pathogens is the most important cause of the disruption of dynamic hemostasis between the oral microbiome and the immune system. Periodontal infection exacerbates the inflammatory response with increased hypoxia and causes vascular changes. The chronicity of inflammation becomes systemic as a link between oral and systemic diseases. The vascular network plays a central role in controlling infection and regulating the immune response. In this review, we focus on the local and systemic vascular network change mechanisms of periodontal inflammation and the pathological processes of inflammatory diseases. Understanding how the vascular network influences the pathology of periodontal diseases and the systemic complication associated with this pathology is essential for the discovery of both local and systemic proactive control mechanisms.
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Affiliation(s)
- Dilek Celik
- Immunology Division, Health Sciences Institute, Trakya University, Edirne 22100, Turkey;
| | - Alpdogan Kantarci
- Forsyth Institute, Cambridge, MA 02142, USA
- School of Dental Medicine, Harvard University, Boston, MA 02142, USA
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Sabharwal A, Stellrecht E, Scannapieco FA. Associations between dental caries and systemic diseases: a scoping review. BMC Oral Health 2021; 21:472. [PMID: 34563194 PMCID: PMC8466895 DOI: 10.1186/s12903-021-01803-w] [Citation(s) in RCA: 56] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Accepted: 09/01/2021] [Indexed: 11/25/2022] Open
Abstract
BACKGROUND The objective of this study was to evaluate and present evidence from animal and human clinical studies on associations between dental caries and systemic diseases, and to suggest potential mechanisms that might explain such associations. METHODS An electronic search was conducted of PubMed, Embase and Cochrane Central Register of Controlled Trials for articles published from 2010 to 2020 in the English language. From the initial search, 404 full-text studies were assessed for eligibility. After excluding studies for technical and study limitations, a total of 67 studies were included in the summary tables and additional studies were included in the review to support evidence. RESULTS Few systemic disease and conditions were found to be clinically meaningfully associated with caries experience. Best evidence from human and animal studies described association between metabolic diseases and dental caries. Several interesting animal studies were noted that could generate clinical hypotheses and further investigations in rodent models for cardiovascular injury and hyperglycemia. Inadequate data was found to suggest any modifications to current clinical practice or prevention guidelines. CONCLUSIONS Limited clinical evidence was found connecting several systemic diseases and dental caries. Inadequate data was found to suggest any modifications to current clinical practice or prevention guidelines. CLINICAL SIGNIFICANCE Understanding of associations between dental caries and systemic diseases play a crucial role in the treatment planning and education of the dental patient.
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Affiliation(s)
- Amarpreet Sabharwal
- Division of Periodontics, Schulich School of Medicine and Dentistry, DSB 0156A, Western University, 1151 Richmond St., London, ON N6A 5C1 Canada
- Department of Periodontics and Endodontics, School of Dental Medicine, University at Buffalo, 3435 Main St., Buffalo, NY 14214 USA
| | - Elizabeth Stellrecht
- Health Sciences Library University at Buffalo, 3435 Main St., Buffalo, NY 14214 USA
| | - Frank A. Scannapieco
- Department of Oral Biology, School of Dental Medicine, University at Buffalo, 3435 Main St, Buffalo, NY 14214 USA
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8
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Portes J, Bullón B, Quiles JL, Battino M, Bullón P. Diabetes Mellitus and Periodontitis Share Intracellular Disorders as the Main Meeting Point. Cells 2021; 10:cells10092411. [PMID: 34572060 PMCID: PMC8467361 DOI: 10.3390/cells10092411] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 09/09/2021] [Accepted: 09/11/2021] [Indexed: 12/15/2022] Open
Abstract
Diabetes and periodontitis are two of the most prevalent diseases worldwide that negatively impact the quality of life of the individual suffering from them. They are part of the chronic inflammatory disease group or, as recently mentioned, non-communicable diseases, with inflammation being the meeting point among them. Inflammation hitherto includes vascular and tissue changes, but new technologies provide data at the intracellular level that could explain how the cells respond to the aggression more clearly. This review aims to emphasize the molecular pathophysiological mechanisms in patients with type 2 diabetes mellitus and periodontitis, which are marked by different impaired central regulators including mitochondrial dysfunction, impaired immune system and autophagy pathways, oxidative stress, and the crosstalk between adenosine monophosphate-activated protein kinase (AMPK) and the renin-angiotensin system (RAS). All of them are the shared background behind both diseases that could explain its relationship. These should be taken in consideration if we would like to improve the treatment outcomes. Currently, the main treatment strategies in diabetes try to reduce glycemia index as the most important aspect, and in periodontitis try to reduce the presence of oral bacteria. We propose to add to the therapeutic guidelines the handling of all the intracellular disorders to try to obtain better treatment success.
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Affiliation(s)
- Juliana Portes
- Department of Periodontology, Dental School, University of Seville, C/Avicena, s/n, 41009 Seville, Spain; (J.P.); (B.B.)
| | - Beatriz Bullón
- Department of Periodontology, Dental School, University of Seville, C/Avicena, s/n, 41009 Seville, Spain; (J.P.); (B.B.)
| | - José Luis Quiles
- Biomedical Research Center (CIBM), Department of Physiology, University Campus of Cartuja, Institute of Nutrition and Food Technology “José Mataix Verdú”, University of Granada, 18071 Granada, Spain;
- Research Group on Foods, Nutritional Biochemistry and Health, Universidad Europea del Atlántico, C/Isabel Torres, 21, 39011 Santander, Spain
| | - Maurizio Battino
- Department of Clinical Sciences, Faculty of Medicine, Università Politecnica delle Marche. Via Tronto 10A, 60126 Torrette di Ancona, Italy;
- International Research Center for Food Nutrition and Safety, Jiangsu University, 301 Xuefu Rd, Zhenjiang 212013, China
| | - Pedro Bullón
- Department of Periodontology, Dental School, University of Seville, C/Avicena, s/n, 41009 Seville, Spain; (J.P.); (B.B.)
- Correspondence:
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El-Baz AM, Shata A, Hassan HM, El-Sokkary MMA, Khodir AE. The therapeutic role of lactobacillus and montelukast in combination with metformin in diabetes mellitus complications through modulation of gut microbiota and suppression of oxidative stress. Int Immunopharmacol 2021; 96:107757. [PMID: 33991997 DOI: 10.1016/j.intimp.2021.107757] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Revised: 04/22/2021] [Accepted: 05/01/2021] [Indexed: 12/25/2022]
Abstract
Male reproductive dysfunction is one of the overlooked findings of diabetes mellitus (DM) that deserves greater scientific attention. This study is designed to explore the therapeutic potential of metformin and montelukast, in combination with Lactobacillus, for modulation of intestinal flora and suppression of oxidative stress in testicular and liver damage in diabetic male rats. A DM model was induced by streptozotocin (STZ)which caused functional, biochemical, and inflammatory injuries to the testicular and liver tissues. The experimental panel included nine rat groups: normal control, normal control plus metformin, normal control plus montelukast, DM control, DM plus montelukast, DM plus a combination of metformin and Lactobacillus, DM plus a combination of montelukast and Lactobacillus, and DM plus a combination of metformin and montelukast. In parallel, clinical evaluation of microscopic examination scoring, and hepatic and testicular injuries, were evaluated. Biochemical markers including glucose level, lipid profile, inflammatory markers (tumor necrosis factor- (TNF-α) and interleukin-17 (IL-17), Caspase-3, and Bax proteins expressions were measured. The change in the microbiota abundance was investigated using conventional and real-time PCR. The current study revealed a significant difference in the relative abundance of microbiota, where DM is associated with an enormous increase of Bacteroides spp., Clostridium spp., E. coli, and Fusobacterium spp., and a significant decrease in Bifidobacteria spp., and Lactobacillus spp., in contrast with normal control. Metformin and montelukast, in combination with Lactobacillus, significantly reversed the testicular and liver damage caused by STZ. Moreover, the drugs significantly reduced the oxidative, inflammatory, and apoptotic activities induced by STZ.
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Affiliation(s)
- Ahmed M El-Baz
- Microbiology and Biotechnology department, Faculty of pharmacy, Delta University for Science and Technology, Gamasa 11152, Egypt.
| | - Ahmed Shata
- Clinical pharmacology department, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt; Clinical Pharmacy department, Faculty of pharmacy, Delta University for Science and Technology, Gamasa 11152, Egypt
| | - Hanan M Hassan
- Pharmacology and biochemistry department, Faculty of pharmacy, Delta University for Science and Technology, Gamasa 11152, Egypt
| | - Mohamed M A El-Sokkary
- Microbiology department, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt
| | - Ahmed E Khodir
- Pharmacology department, Faculty of pharmacy, Horus University-Egypt, New Damietta 34518, Egypt
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Yamamoto R, Amano K, Takahashi SW, To M, Takahashi S, Matsuo M. Changes in the microcirculation in periodontal tissue due to experimental peri-implantitis. J Oral Biosci 2021; 63:153-160. [PMID: 33746071 DOI: 10.1016/j.job.2021.03.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 03/04/2021] [Accepted: 02/20/2021] [Indexed: 01/24/2023]
Abstract
OBJECTIVES Peri-implantitis causes dislodgement of dental implants due to inflammation in the peri-implant tissue. The microcirculation in the periodontal tissue undergoes morphological and physiological changes due to inflammation. The immune mechanism of peri-implantitis differs from that of periodontitis. In this study, we examined the changes in the microcirculation in the peri-implant tissue with experimentally induced inflammation, using morphological and physiological techniques. METHODS Six beagle dogs were used in the experiment. After extracting both mandibular premolars, three titanium screw implants were inserted on each side of the mandibular jaw. Dental floss was placed on the right side for 90 days in the study group but not in the control group. Microvascular resin cast models were created, and morphological changes were observed using scanning electron microscopy. Periodontal blood flow was measured using laser Doppler flowmetry. RESULTS Ninety days after induction of inflammation, bone resorption was observed around the implant body. Osseointegration was impaired, and a gap at the implant-bone interface was observed. The resin cast models showed that inflamed gingival blood vessels had invaded the bone marrow through the resorbed apical margin of the alveolar bone. Analysis of the physiological data obtained using laser Doppler flowmetry showed a significant increase in blood flow around the implants with experimentally induced inflammation. CONCLUSIONS Significant morphological and physiological changes occur in the gingival microcirculation of peri-implant tissue due to inflammation. Evaluating the vasculature and blood flow in the tissue surrounding the site of peri-implantitis may be helpful for pathologic analysis in clinical settings.
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Affiliation(s)
- Reiko Yamamoto
- Department of Oral Science, Kanagawa Dental University, Graduate School of Dentistry, Japan
| | - Kaori Amano
- Department of Oral Science, Kanagawa Dental University, Graduate School of Dentistry, Japan
| | - Satoko-Wada Takahashi
- Department of Oral Science, Kanagawa Dental University, Graduate School of Dentistry, Japan
| | - Masahiro To
- Department of Oral Science, Kanagawa Dental University, Graduate School of Dentistry, Japan
| | - Shunsuke Takahashi
- Department of Oral Science, Kanagawa Dental University, Graduate School of Dentistry, Japan
| | - Masato Matsuo
- Department of Oral Science, Kanagawa Dental University, Graduate School of Dentistry, Japan.
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11
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Yamamoto Y, Morozumi T, Hirata T, Takahashi T, Fuchida S, Toyoda M, Nakajima S, Minabe M. Effect of Periodontal Disease on Diabetic Retinopathy in Type 2 Diabetic Patients: A Cross-sectional Pilot Study. J Clin Med 2020; 9:E3234. [PMID: 33050355 PMCID: PMC7600038 DOI: 10.3390/jcm9103234] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Revised: 10/06/2020] [Accepted: 10/07/2020] [Indexed: 11/16/2022] Open
Abstract
Both periodontal disease and diabetes are common chronic inflammatory diseases. One of the major problems with type 2 diabetes is that unregulated blood glucose levels damage the vascular endothelium and cause complications. A bidirectional relationship between periodontal disease and diabetic complications has been reported previously. However, whether periodontal disease affects the presence of diabetic complications has not been clarified. Therefore, we examined the effect of the periodontal disease status on diabetic complications in patients with type 2 diabetes. Periodontal doctors examined the periodontal disease status of 104 type 2 diabetic patients who visited a private diabetes medical clinic once a month between 2016 and 2018. The subject's diabetic status was obtained from their medical records. Bayesian network analysis showed that bleeding on probing directly influenced the presence of diabetic retinopathy in type 2 diabetes patients. In addition, bleeding on probing was higher in the diabetic retinopathy group (n = 36) than in the group without diabetic retinopathy (n = 68, p = 0.006, Welch's t-test). Bleeding on probing represents gingival inflammation, which might affect the presence of diabetic retinopathy in type 2 diabetes patients who regularly visit diabetic clinics.
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Affiliation(s)
- Yuko Yamamoto
- Department of Dental Hygiene, Kanagawa Dental University, Junior College, 82 Inaoka, Yokosuka 2388580, Kanagawa, Japan;
| | - Toshiya Morozumi
- Division of Periodontology, Department of Oral Interdisciplinary Medicine, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka, Yokosuka 2388580, Kanagawa, Japan; (T.H.); (M.M.)
| | - Takahisa Hirata
- Division of Periodontology, Department of Oral Interdisciplinary Medicine, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka, Yokosuka 2388580, Kanagawa, Japan; (T.H.); (M.M.)
| | - Toru Takahashi
- Department of Health and Nutrition, Faculty of Human Health, Kanazawa Gakuin University, 10 Sue-machi, Kanazawa 9201392, Ishikawa, Japan;
| | - Shinya Fuchida
- Department of Disaster Medicine and Dental Sociology, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka, Yokosuka 2388580, Kanagawa, Japan;
| | - Masami Toyoda
- Nakajima Internal Medicine Clinic, 1-17 Yonegahamadori, Yokosuka 2380011, Kanagawa, Japan; (M.T.); (S.N.)
| | - Shigeru Nakajima
- Nakajima Internal Medicine Clinic, 1-17 Yonegahamadori, Yokosuka 2380011, Kanagawa, Japan; (M.T.); (S.N.)
| | - Masato Minabe
- Division of Periodontology, Department of Oral Interdisciplinary Medicine, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka, Yokosuka 2388580, Kanagawa, Japan; (T.H.); (M.M.)
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12
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Kuraji R, Wu YH, Hashimoto S, Mishiro S, Maeda Y, Miyashita Y, Ito H, Miwa Y, Sunohara M, Kapila Y, Numabe Y. Temporal and dynamic changes in gingival blood flow during progression of ligature-induced periodontitis. Oral Dis 2020; 26:1292-1301. [PMID: 32153097 DOI: 10.1111/odi.13328] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2019] [Revised: 02/13/2020] [Accepted: 03/04/2020] [Indexed: 12/16/2022]
Abstract
OBJECTIVES To evaluate temporal changes in gingival blood flow (GBF) during progression of periodontitis in rats using a laser Doppler flowmeter (LDF) approach and to characterize morphological and biochemical features in the periodontium associated with GBF. MATERIALS AND METHODS Forty-two Wistar rats were divided into a ligature-induced periodontitis group and a control group. To induce periodontitis, ligatures were tied around maxillary first molars bilaterally. GBF was measured in palatal gingiva at pretreatment and following ligature placement after 30 min, 1, 3, 7, 14, 21, and 28 days using LDF with a non-contact probe. Bone loss and gene expression in gingival tissues were assessed using micro-computed tomography (μCT) and quantitative polymerase chain reaction (PCR), respectively. Immunostaining for vascular endothelial growth factor (VEGF) in the maxilla was also histologically evaluated. RESULTS GBF in the ligature group increased significantly compared with the control group 30 min after ligation. However, on days 3 and 7, GBF decreased in the ligature group. Also, after day 10, there was no difference in GBF between groups. The levels of alveolar bone loss, gene expression (interleukin-6, cluster of differentiation-31, VEGF-A, and lymphatic vessel endothelial hyaluronan receptor-1), and immunostained VEGF-positive vessels correlated well with changes in GBF. CONCLUSION PROGRESSION OF PERIODONTITIS: In rats was associated with a triphasic pattern of GBF, consisting of a short initial increase, followed by a rapid decrease, and then a gradual plateau phase.
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Affiliation(s)
- Ryutaro Kuraji
- Department of Life Science Dentistry, The Nippon Dental University, Tokyo, Japan
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
- Department of Orofacial Sciences, School of Dentistry, University of California San Francisco, San Francisco, CA, USA
| | - Ya-Hsin Wu
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
- Department of periodontology, China medical University Hospital, Taichung City, Taiwan
| | | | - Saki Mishiro
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
| | - Yuuki Maeda
- Department of General Dentistry, The Nippon Dental University Hospital, Tokyo, Japan
| | - Yukihiro Miyashita
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
| | - Hiroshi Ito
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
| | - Yoko Miwa
- Department of Anatomy, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
| | - Masataka Sunohara
- Department of Anatomy, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
| | - Yvonne Kapila
- Department of Orofacial Sciences, School of Dentistry, University of California San Francisco, San Francisco, CA, USA
| | - Yukihiro Numabe
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Tokyo, Tokyo, Japan
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13
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Vicente A, Bravo-González LA, Navarro JA, Buendía AJ, Camacho-Alonso F. Effects of diabetes on oxidative stress, periodontal ligament fiber orientation, and matrix metalloproteinase 8 and 9 expressions during orthodontic tooth movement. Clin Oral Investig 2020; 25:1383-1394. [PMID: 32643088 DOI: 10.1007/s00784-020-03446-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Accepted: 07/03/2020] [Indexed: 12/26/2022]
Abstract
OBJECTIVES To evaluate the influence of diabetes on oxidative stress, periodontal ligament (PDL) orientation, and matrix metalloproteinase (MMP) 8 and 9 expressions during orthodontic tooth movement in a rat model. MATERIALS AND METHODS An orthodontic appliance was placed in 60 Sprague-Dawley rats divided into three groups: normoglycemics (n = 20) and two streptozotocin-induced diabetic groups, one untreated (n = 20) and one insulin-treated (n = 20). At 24, 48, and 72 h and 1 week, rats were sacrificed. At each time point, myeloperoxidase (MPO) and malondialdehyde (MDA) were quantified by spectrophotometry, tooth movement was evaluated by micro-CT analysis, and hematoxylin and eosin staining was used to evaluate PDL fiber orientation and immunohistochemistry staining with semi-quantitative H-score analysis of MMP-8 and MMP-9 was performed.. RESULTS At 24 h, MPO activity was significantly higher in untreated-diabetics than normoglycemics. At 24 and 48 h, the MDA level in untreated-diabetic rats was significantly higher than in normoglycemics and insulin-treated animals. At 72 h and 1 week, PDL fibers were oriented significantly more irregularly in untreated-diabetics than in normoglycemics. At all time points, MMP-8 and MMP-9 expressions were significantly higher in both diabetic groups than in the normoglycemic group. After the second day, tooth movement was significantly greater in untreated-diabetics than in the insulin-treated and normoglycemic groups. CONCLUSIONS Mechanical stress in untreated-diabetic rats produces more inflammatory response, oxidative stress, tooth movement, PDL disorganization, and MMP-8 and MMP-9 expressions than among normoglycemics. Insulin reverses these effects, favoring the reorganization of periodontal ligament. CLINICAL RELEVANCE Our results suggest that the application of orthodontic force in diabetic patients would increase inflammation and delay periodontal restructuring. Insulin would partly reverse this situation although glycemic decompensation episodes may occur. For these reasons, the periods between fixed orthodontic appliance activations should be of sufficient duration to allow adequate tissue recovery.
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Affiliation(s)
- Ascensión Vicente
- Unit of Orthodontics, University Dental Clinic, Faculty of Medicine, University of Murcia, Murcia, Spain
| | | | - J A Navarro
- Department of Histology and Pathological Anatomy, University of Murcia, Murcia, Spain
| | - A J Buendía
- Department of Histology and Pathological Anatomy, University of Murcia, Murcia, Spain
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14
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Komatsu T, Kobayashi K, Morimoto Y, Helmerhorst E, Oppenheim F, Chang-Il Lee M. Direct evaluation of the antioxidant properties of salivary proline-rich proteins. J Clin Biochem Nutr 2020; 67:131-136. [PMID: 33041509 PMCID: PMC7533858 DOI: 10.3164/jcbn.19-75] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2019] [Accepted: 11/10/2019] [Indexed: 01/20/2023] Open
Abstract
Proline-rich proteins are associated with the formation of an acquired protein layer overlying the tooth enamel surface. Previous studies have described the antioxidant activity of salivary histatin against the hydroxyl radical from Fenton’s reaction, acting as the critical reactive oxygen species. However, the role of proline-rich proteins in mitigating the oxidative stress caused by reactive oxygen species in the oral cavity remains unclear. In this study, we investigated the antioxidant effects of proline-rich proteins 2 on direct reactive oxygen species using electron spin resonance spectroscopy. For the first time, we demonstrated that proline-rich proteins 2 exhibits antioxidant activity directly against the hydroxyl radical produced by hydrogen peroxide with ultraviolet. Considering that identical results were obtained when assaying 30 residues of proline-rich proteins 2, the direct antioxidant effects against the hydroxyl radical by proline-rich proteins 2 may be related to these specific 30 residues.
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Affiliation(s)
- Tomoko Komatsu
- Division of Dentistry for the Special Patient, Department of Critical Care Medicine and Dentistry, Kanagawa Dental University Graduate School of Dental Medicine, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan.,Yokosuka-Shonan Disaster Oral Health Research Center & Oxidative Stress/ESR Laboratories, Kanagawa Dental University Graduate School of Dental Medicine, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Kyo Kobayashi
- Yokosuka-Shonan Disaster Oral Health Research Center & Oxidative Stress/ESR Laboratories, Kanagawa Dental University Graduate School of Dental Medicine, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Yoshinari Morimoto
- Department of Critical Care Medicine and Dentistry, Kanagawa Dental University Graduate School of Dental Medicine, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Eva Helmerhorst
- Department of Molecular and Cell Biology, Boston University Henry M. Goldman School of Dental Medicine, Albany street, Boston, MA 02118, USA
| | - Frank Oppenheim
- Department of Molecular and Cell Biology, Boston University Henry M. Goldman School of Dental Medicine, Albany street, Boston, MA 02118, USA
| | - Masaichi Chang-Il Lee
- Yokosuka-Shonan Disaster Oral Health Research Center & Oxidative Stress/ESR Laboratories, Kanagawa Dental University Graduate School of Dental Medicine, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
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15
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Wada-Takahashi S, Hidaka KI, Yoshino F, Yoshida A, Tou M, Matsuo M, Takahashi SS. Effect of physical stimulation (gingival massage) on age-related changes in gingival microcirculation. PLoS One 2020; 15:e0233288. [PMID: 32433681 PMCID: PMC7239467 DOI: 10.1371/journal.pone.0233288] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2019] [Accepted: 05/03/2020] [Indexed: 11/18/2022] Open
Abstract
The decline in circulatory function with aging may be alleviated by a combination of gingival massage (physical stimulation) and mechanical cleaning. Several studies have reported the systemic effect of physical stimulation on various parts of the body, including its therapeutic effect on pain in the neck and shoulders that becomes evident with age, and improvement in blood circulation. In contrast, few studies have reported on the changes in gingival microcirculation induced by gingival massage, while no previous study has evaluated the effect of gingival microcirculation on age-related changes in the hemodynamics of the oral cavity. This study aimed to investigate how gingival massage affects age-related changes in gingival microcirculation. Male Wistar rats (7-week, 6-month and 1-year old) were prepared for a gingival massage group and a control group. Mechanical stimulation was applied on the maxillary molar gingiva for 5 seconds twice a week for 4 weeks. Subsequently, gingival reactive hyperemia was measured using a laser Doppler flowmeter. In addition, morphological analyses were also performed by hematoxylin and eosin and Indian ink staining and a vascular resin cast model. Base Flow, maximum response (Peak), and time required for the maximum response to halve (T1/2) were reduced in 1-year-old rats compared with the other age groups. In the mechanical stimulated group, T1/2 was increased in 7-week, 6-month, and 1-year-old rats, and total blood flow (Mass) was increased in 6-month and 1-year-old rats. In addition, clear blood vessel networks and loop-like revascularization were only observed in the mechanical stimulated group. Changes in age-related decline in gingival microcirculatory function and vascular construction were reported in this study, and the results suggested that gingival massage activates both the functional and morphological aspects of gingival microcirculation and may be effective for maintaining oral health.
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Affiliation(s)
- Satoko Wada-Takahashi
- Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, Yokosuka, Kanagawa, Japan
- * E-mail: (SWT); (SST)
| | - Ko-ichi Hidaka
- Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, Yokosuka, Kanagawa, Japan
| | - Fumihiko Yoshino
- Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, Yokosuka, Kanagawa, Japan
| | - Ayaka Yoshida
- Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, Yokosuka, Kanagawa, Japan
| | - Masahiro Tou
- Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, Yokosuka, Kanagawa, Japan
| | - Masato Matsuo
- Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, Yokosuka, Kanagawa, Japan
| | - Shun-suke Takahashi
- Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, Yokosuka, Kanagawa, Japan
- * E-mail: (SWT); (SST)
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16
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Barakat KI, Elborolosy SA. Does diabetes mellitus affect the parotid ductal system? A sialendoscopic evaluation. Oral Surg Oral Med Oral Pathol Oral Radiol 2020; 129:e243-e248. [PMID: 32111580 DOI: 10.1016/j.oooo.2019.09.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2019] [Revised: 09/02/2019] [Accepted: 09/08/2019] [Indexed: 10/26/2022]
Abstract
OBJECTIVE The aim of this study was to assess the existence of ductal changes in diabetics using sialendoscopy. STUDY DESIGN Twenty patients and 10 volunteers received bilateral parotid diagnostic sialendoscopy. Group I included 10 patients with uncontrolled diabetes (UCD); group II, 10 patients with controlled diabetes (CD); and group III, 10 nondiabetic controls (CG). Expected ductal changes were examined in 3 proposed distinct zones. A χ2 test was used to compare groups. RESULTS Ductal pathologic conditions were significantly higher in diabetic patients in all zones. Abnormalities were classified as stenosis, hyperemia, or others. In UCD, stenosis percentage was 55%, 90%, and 100% in zones 1, 2, and 3, respectively, compared with 30%, 40%, and 55% in CD and 5%, 5%, and 0% in CG (P < .01). Hyperemic changes in UCD were 90%, 90%, and 40% compared with 50%, 50%, and 20% in CD (P < .01) and 0% in CG. Comparing zones in UCD and CD indicated that stenosis increased significantly toward the proximal end, whereas hyperemia prevailed toward the distal end. CONCLUSIONS Significant ductal abnormalities were detected in the parotids of UCD and CD patients compared with CG. Ductal changes were higher in UCD compared with CD.
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Affiliation(s)
- Khaled Ibrahim Barakat
- Professor and Head of Oral and Maxillofacial Surgery Department, Faculty of Dentistry, Minia University, Minia, Egypt; General Manager of Cranio-Maxillofacial Surgery Unit, Faculty of Dentistry, Minia University, Minia, Egypt; Director of Shifa Oral and Maxillofacial Surgery Center, Cairo, Egypt.
| | - Samir Ali Elborolosy
- Lecturer, Oral and Maxillofacial Surgery Department Faculty of Dentistry, Beni Suef University, Beni Suef, Egypt
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17
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Sun Z, Xiong C, Teh SW, Lim JCW, Kumar S, Thilakavathy K. Mechanisms of Oral Bacterial Virulence Factors in Pancreatic Cancer. Front Cell Infect Microbiol 2019; 9:412. [PMID: 31867287 PMCID: PMC6904357 DOI: 10.3389/fcimb.2019.00412] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2019] [Accepted: 11/19/2019] [Indexed: 12/19/2022] Open
Abstract
Pancreatic cancer is a highly lethal disease, and most patients remain asymptomatic until the disease enters advanced stages. There is lack of knowledge in the pathogenesis, effective prevention and early diagnosis of pancreatic cancer. Recently, bacteria were found in pancreatic tissue that has been considered sterile before. The distribution of flora in pancreatic cancer tissue was reported to be different from normal pancreatic tissue. These abnormally distributed bacteria may be the risk factors for inducing pancreatic cancer. Therefore, studies on combined effect of multi-bacterial and multi-virulence factors may add to the knowledge of pancreatic cancer pathogenesis and aid in designing new preventive and therapeutic strategies. In this review, we outlined three oral bacteria associated with pancreatic cancer and their virulence factors linked with cancer.
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Affiliation(s)
- Zhong Sun
- Department of Biomedical Science, Universiti Putra Malaysia, Serdang, Malaysia
| | - ChengLong Xiong
- Department of Public Health Microbiology, School of Public Health, Fudan University, Shanghai, China
| | - Seoh Wei Teh
- Department of Medical Microbiology and Parasitology, Universiti Putra Malaysia, Serdang, Malaysia
| | - Jonathan Chee Woei Lim
- Pharmacotherapeutics Unit, Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia
| | - Suresh Kumar
- Department of Medical Microbiology and Parasitology, Universiti Putra Malaysia, Serdang, Malaysia.,Genetics and Regenerative Medicine Research Centre, Universiti Putra Malaysia, Serdang, Malaysia.,UPM-MAKNA Cancer Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Malaysia
| | - Karuppiah Thilakavathy
- Department of Biomedical Science, Universiti Putra Malaysia, Serdang, Malaysia.,Genetics and Regenerative Medicine Research Centre, Universiti Putra Malaysia, Serdang, Malaysia
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18
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Komatsu T, Kobayashi K, Helmerhorst E, Oppenheim F, Chang-Il Lee M. Direct assessment of the antioxidant property of salivary histatin. J Clin Biochem Nutr 2019; 65:217-222. [PMID: 31777423 PMCID: PMC6877405 DOI: 10.3164/jcbn.19-53] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2019] [Accepted: 08/17/2019] [Indexed: 11/22/2022] Open
Abstract
Histatin, a salivary protein, affects oral homeostasis through preservation of tooth integrity and protection against caries and fungal infections. However, the effects of histatin in the generation of oxidative stress induced by reactive oxygen species and in the oral cavity remain unclear. In this study, the effects of histatin on direct reactive oxygen species scavenging activity were examined using electron spin resonance. We demonstrated, for the first time, that histatin exhibits antioxidant activity against hydroxyl radicals generated by Fenton's reaction by metal chelation or binding. The direct antioxidant effects of histatin, along with its antimicrobial activity, may be important in the oral protection of salivary proteins.
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Affiliation(s)
- Tomoko Komatsu
- Division of Dentistry for the Special Patient, Department of Critical Care Medicine and Dentistry, Kanagawa Dental University Graduate School of Dental Medicine, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan.,Yokosuka-Shonan Disaster Oral Health Research Center & Oxidative Stress/ESR Laboratories, Kanagawa Dental University Graduate School of Dental Medicine, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Kyo Kobayashi
- Yokosuka-Shonan Disaster Oral Health Research Center & Oxidative Stress/ESR Laboratories, Kanagawa Dental University Graduate School of Dental Medicine, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Eva Helmerhorst
- Department of Molecular and Cell Biology, Boston University Henry M. Goldman School of Dental Medicine, Albany street, Boston, MA 02118, USA
| | - Frank Oppenheim
- Department of Molecular and Cell Biology, Boston University Henry M. Goldman School of Dental Medicine, Albany street, Boston, MA 02118, USA
| | - Masaichi Chang-Il Lee
- Yokosuka-Shonan Disaster Oral Health Research Center & Oxidative Stress/ESR Laboratories, Kanagawa Dental University Graduate School of Dental Medicine, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
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19
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Meghil MM, Tawfik OK, Elashiry M, Rajendran M, Arce RM, Fulton DJ, Schoenlein PV, Cutler CW. Disruption of Immune Homeostasis in Human Dendritic Cells via Regulation of Autophagy and Apoptosis by Porphyromonas gingivalis. Front Immunol 2019; 10:2286. [PMID: 31608069 PMCID: PMC6769118 DOI: 10.3389/fimmu.2019.02286] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Accepted: 09/10/2019] [Indexed: 12/11/2022] Open
Abstract
As fundamental processes of immune homeostasis, autophagy, and apoptosis must be maintained to mitigate risk of chronic inflammation and autoimmune diseases. Periodontitis is a chronic inflammatory disease characterized by oral microbial dysbiosis, and dysregulation of dendritic cell (DC) and T cell responses. The aim of this study was to elucidate the underlying mechanisms by which the oral microbe Porphyromonas gingivalis (P. gingivalis) manipulates dendritic cell signaling to perturb both autophagy and apoptosis. Using a combination of Western blotting, flow cytometry, qRT-PCR and immunofluorescence analysis, we show a pivotal role for the minor (Mfa1) fimbriae of P. gingivalis in nuclear/cytoplasmic shuttling of Akt and FOXO1 in human monocyte-derived DCs. Mfa1-induced Akt nuclear localization and activation ultimately induced mTOR. Activation of the Akt/mTOR axis downregulated intracellular LC3II, also known as Atg8, required for autophagosome formation and maturation. Use of allosteric panAkt inhibitor MK2206 and mTOR inhibitor rapamycin confirmed the role of Akt/mTOR signaling in autophagy inhibition by P. gingivalis in DCs. Interestingly, this pathway was also linked to induction of the anti-apoptotic protein Bcl2, decreased caspase-3 cleavage and decreased expression of pro-apoptotic proteins Bax and Bim, thus promoting longevity of host DCs. Addition of ABT-199 peptide to disrupt the interaction of antiapoptotic Bcl2 and its proapoptotic partners BAK/BAX restored apoptotic death to P. gingivalis-infected DC cells. In summary, we have identified the underlying mechanism by which P. gingivalis promotes its own survival and that of its host DCs.
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Affiliation(s)
- Mohamed M Meghil
- Department of Periodontics, Dental College of Georgia at Augusta University, Augusta, GA, United States.,Department of Oral Biology and Diagnostic Sciences, Dental College of Georgia at Augusta University, Augusta, GA, United States
| | - Omnia K Tawfik
- Department of Periodontics, Dental College of Georgia at Augusta University, Augusta, GA, United States
| | - Mahmoud Elashiry
- Department of Periodontics, Dental College of Georgia at Augusta University, Augusta, GA, United States.,Department of Oral Biology and Diagnostic Sciences, Dental College of Georgia at Augusta University, Augusta, GA, United States
| | - Mythilypriya Rajendran
- Department of Periodontics, Dental College of Georgia at Augusta University, Augusta, GA, United States
| | - Roger M Arce
- Department of Periodontics, Dental College of Georgia at Augusta University, Augusta, GA, United States
| | - David J Fulton
- Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, GA, United States
| | - Patricia V Schoenlein
- Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, GA, United States
| | - Christopher W Cutler
- Department of Periodontics, Dental College of Georgia at Augusta University, Augusta, GA, United States
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20
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Association between periodontal pathogens and systemic disease. Biomed J 2019; 42:27-35. [PMID: 30987702 PMCID: PMC6468093 DOI: 10.1016/j.bj.2018.12.001] [Citation(s) in RCA: 419] [Impact Index Per Article: 69.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2018] [Revised: 11/22/2018] [Accepted: 12/04/2018] [Indexed: 12/13/2022] Open
Abstract
A growing body of literature suggests that there is a link between periodontitis and systemic diseases. These diseases include cardiovascular disease, gastrointestinal and colorectal cancer, diabetes and insulin resistance, and Alzheimer's disease, as well as respiratory tract infection and adverse pregnancy outcomes. The presence of periodontal pathogens and their metabolic by-products in the mouth may in fact modulate the immune response beyond the oral cavity, thus promoting the development of systemic conditions. A cause-and-effect relationship has not been established yet for most of the diseases, and the mediators of the association are still being identified. A better understanding of the systemic effects of oral microorganisms will contribute to the goal of using the oral cavity to diagnose and possibly treat non-oral systemic disease.
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21
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Fazekas R, Molnár E, Lohinai Z, Dinya E, Tóth Z, Windisch P, Vág J. Functional characterization of collaterals in the human gingiva by laser speckle contrast imaging. Microcirculation 2019; 25:e12446. [PMID: 29457306 DOI: 10.1111/micc.12446] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2017] [Accepted: 02/13/2018] [Indexed: 11/30/2022]
Abstract
OBJECTIVE The rate of blood flow between the various areas of the gingiva in resting position and under challenge is unknown. In this study, the LSCI method was used to map spatial and temporal changes in gingival blood flow after transient compression. METHODS Horizontal, vertical, and papilla base compressions were applied on the attached gingiva in 21 healthy patients (13 women, 8 men). LSCI was used to determine dynamic changes in regional blood flow during a five-second occlusion interval and subsequent reperfusion for twenty minutes. RESULTS Resting blood flow in the attached gingiva apical to the papillae was higher as compared to that in the midbuccal area of the teeth. During short-term horizontal compression, ischemia was greater coronal than apical to the occlusion line. Postocclusive hyperemia was observed not only in the regions affected by ischemia but encompassed a wider area. Hyperemic response was more pronounced and prolonged in male than in female patients. CONCLUSIONS Blood flow in the attached gingiva shows spatial differences. Our findings corroborate the apicocoronal orientation of blood circulation. Periodontal and papillary collaterals may have little role in the blood supply of the adjacent attached gingiva under physiological conditions.
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Affiliation(s)
- Réka Fazekas
- Department of Conservative Dentistry, Faculty of Dentistry, Semmelweis University, Budapest, Hungary
| | - Eszter Molnár
- Department of Conservative Dentistry, Faculty of Dentistry, Semmelweis University, Budapest, Hungary
| | - Zsolt Lohinai
- Department of Conservative Dentistry, Faculty of Dentistry, Semmelweis University, Budapest, Hungary
| | - Elek Dinya
- Institute of Digital Health Sciences, Faculty of Health and Public Services, Semmelweis University, Budapest, Hungary
| | - Zsuzsanna Tóth
- Department of Conservative Dentistry, Faculty of Dentistry, Semmelweis University, Budapest, Hungary
| | - Péter Windisch
- Department of Periodontology, Faculty of Dentistry, Semmelweis University, Budapest, Hungary
| | - János Vág
- Department of Conservative Dentistry, Faculty of Dentistry, Semmelweis University, Budapest, Hungary
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22
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Verhulst MJL, Loos BG, Gerdes VEA, Teeuw WJ. Evaluating All Potential Oral Complications of Diabetes Mellitus. Front Endocrinol (Lausanne) 2019; 10:56. [PMID: 30962800 PMCID: PMC6439528 DOI: 10.3389/fendo.2019.00056] [Citation(s) in RCA: 137] [Impact Index Per Article: 22.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2018] [Accepted: 01/22/2019] [Indexed: 12/13/2022] Open
Abstract
Diabetes mellitus (DM) is associated with several microvascular and macrovascular complications, such as retinopathy, nephropathy, neuropathy, and cardiovascular diseases. The pathogenesis of these complications is complex, and involves metabolic and hemodynamic disturbances, including hyperglycemia, insulin resistance, dyslipidemia, hypertension, and immune dysfunction. These disturbances initiate several damaging processes, such as increased reactive oxygen species (ROS) production, inflammation, and ischemia. These processes mainly exert their damaging effect on endothelial and nerve cells, hence the susceptibility of densely vascularized and innervated sites, such as the eyes, kidneys, and nerves. Since the oral cavity is also highly vascularized and innervated, oral complications can be expected as well. The relationship between DM and oral diseases has received considerable attention in the past few decades. However, most studies only focus on periodontitis, and still approach DM from the limited perspective of elevated blood glucose levels only. In this review, we will assess other potential oral complications as well, including: dental caries, dry mouth, oral mucosal lesions, oral cancer, taste disturbances, temporomandibular disorders, burning mouth syndrome, apical periodontitis, and peri-implant diseases. Each oral complication will be briefly introduced, followed by an assessment of the literature studying epidemiological associations with DM. We will also elaborate on pathogenic mechanisms that might explain associations between DM and oral complications. To do so, we aim to expand our perspective of DM by not only considering elevated blood glucose levels, but also including literature about the other important pathogenic mechanisms, such as insulin resistance, dyslipidemia, hypertension, and immune dysfunction.
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Affiliation(s)
- Martijn J. L. Verhulst
- Department of Periodontology, Academic Centre for Dentistry Amsterdam, University of Amsterdam and Vrije Universiteit, Amsterdam, Netherlands
- *Correspondence: Martijn J. L. Verhulst
| | - Bruno G. Loos
- Department of Periodontology, Academic Centre for Dentistry Amsterdam, University of Amsterdam and Vrije Universiteit, Amsterdam, Netherlands
| | - Victor E. A. Gerdes
- Department of Vascular Medicine, Amsterdam UMC, Amsterdam, Netherlands
- Department of Internal Medicine, Spaarne Gasthuis, Hoofddorp, Netherlands
| | - Wijnand J. Teeuw
- Department of Periodontology, Academic Centre for Dentistry Amsterdam, University of Amsterdam and Vrije Universiteit, Amsterdam, Netherlands
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Molnár E, Fazekas R, Lohinai Z, Tóth Z, Vág J. Assessment of the test-retest reliability of human gingival blood flow measurements by Laser Speckle Contrast Imaging in a healthy cohort. Microcirculation 2018; 25. [PMID: 28976050 DOI: 10.1111/micc.12420] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2017] [Accepted: 09/26/2017] [Indexed: 12/23/2022]
Abstract
OBJECTIVE The reliability of gingival blood flow measured by Laser Speckle Contrast Imaging is unknown. Our aim was to investigate the effect of factors inherent in oral mucosa measurement on intra-day and inter-day reliability. METHODS Gingival blood flow was measured in seventy healthy subjects. First, measurements were obtained by varying the incidence angle of imaging, using a lip retractor. Second, 3 snapshots were taken with closure of the mouth in-between, and lips were retracted by a dental mirror. These were repeated 1 week later. Third, snapshots were taken either by direct view or using a mirror. Reliability was assessed based on coefficient of variation. RESULTS Unlike retraction of the lips and the mirror, the incidence angle had an effect on mean blood flow. The coefficient of variation within a subject was 6.4% with the mouth constantly open. With retraction, the intra-session, and the inter-day coefficient of variation were 8.3% and 10.5%, respectively. The coefficient of variation was 11.9% by alternating direct and indirect imaging. CONCLUSIONS Laser Speckle Contrast Imaging has good short- and long-term reliability regardless of lip retraction or an indirect view. This technique seems to be appropriate for the long-term clinical non-invasive follow-up of gingival microcirculation.
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Affiliation(s)
- Eszter Molnár
- Department of Conservative Dentistry, Faculty of Dentistry, Semmelweis University, Budapest, Hungary
| | - Réka Fazekas
- Department of Conservative Dentistry, Faculty of Dentistry, Semmelweis University, Budapest, Hungary
| | - Zsolt Lohinai
- Department of Conservative Dentistry, Faculty of Dentistry, Semmelweis University, Budapest, Hungary
| | - Zsuzsanna Tóth
- Department of Conservative Dentistry, Faculty of Dentistry, Semmelweis University, Budapest, Hungary
| | - János Vág
- Department of Conservative Dentistry, Faculty of Dentistry, Semmelweis University, Budapest, Hungary
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Suzuki M, Toyama T, Watanabe K, Sasaki H, Sugiyama S, Yoshino F, Yoshida A, Takahashi SS, Wada-Takahashi S, Matsuo M, Todoki K, Hamada N. Ameliorating Effects of Jixueteng in a Mouse Model of Porphyromonas gingivalis-Induced Periodontitis: Analysis Based on Gingival Microcirculatory System. Nat Prod Commun 2018. [DOI: 10.1177/1934578x1801301230] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Jixueteng, the dried stem of Spatholobus suberectus Dunn (Leguminosae), is a traditional Chinese herbal medicine that promotes blood circulation and can be used to treat blood stasis. In this study, we aimed to investigate the potential of Jixueteng as a preventive and therapeutic drug for periodontitis. We investigated the inhibitory effects of Jixueteng on Porphyromonas gingivalis ( P. gingivalis)-induced gingival circulatory disturbances in mice. Seventy-two male C57BL/6N mice (4-week-old) were randomly divided into the following four groups of 12 mice each. Group 1 served as the P. gingivalis noninfected control (control group). Group 2 was administered Jixueteng extract in drinking water to P. gingivalis noninfected control mice. Group 3 was infected orally with P. gingivalis; and group 4 was administered Jixueteng extract in drinking water and then infected with P. gingivalis. To evaluate the effect of Jixueteng on gingival microcirculation systems, we examined gingival blood flow (GBF) in oral microcirculation in vivo in a mouse model of periodontitis. Gingival reactive hyperemia (GRH) was determined using laser Doppler flowmetry. GRH was elicited by the release of occlusive gingival compression by the laser Doppler probe (diameter 1.0 mm) for 1 min. GRH was estimated by basal blood flow, maximum response (Peak), the time taken for the maximum response to fall to one half (T1/2) and increased total amount of blood flow (Mass). Furthermore, to determine the effect of an oral application of P. gingivalis and/or Jixueteng on GBF and gingival microvessel ultrastructure, morphological analysis of gingival microvessels was performed by using a vascular resin cast model. Administration of Jixueteng to P. gingivalis-infected animals significantly reduced GRH, especially T1/2 and Mass, compared to that in P. gingivalis-infected animals. Alternatively, in the morphological analysis, reduction of the gingival capillary network which resulted from P. gingivalis-infection was improved by Jixueteng administration. Since Jixueteng ameliorates P. gingivalis infection-induced gingival circulatory disturbance, it may be useful in the treatment of P. gingivalis-induced periodontitis.
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Affiliation(s)
- Mitsuo Suzuki
- Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Toshizo Toyama
- Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Kiyoko Watanabe
- Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Haruka Sasaki
- Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Shuta Sugiyama
- Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Fumihiko Yoshino
- Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Ayaka Yoshida
- Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Shun-suke Takahashi
- Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Satoko Wada-Takahashi
- Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Masato Matsuo
- Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Kazuo Todoki
- Department of Health Science, School of Nursing, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Nobushiro Hamada
- Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
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Carter CJ, France J, Crean S, Singhrao SK. The Porphyromonas gingivalis/Host Interactome Shows Enrichment in GWASdb Genes Related to Alzheimer's Disease, Diabetes and Cardiovascular Diseases. Front Aging Neurosci 2017; 9:408. [PMID: 29311898 PMCID: PMC5732932 DOI: 10.3389/fnagi.2017.00408] [Citation(s) in RCA: 58] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2017] [Accepted: 11/27/2017] [Indexed: 12/13/2022] Open
Abstract
Periodontal disease is of established etiology in which polymicrobial synergistic ecology has become dysbiotic under the influence of Porphyromonas gingivalis. Following breakdown of the host's protective oral tissue barriers, P. gingivalis migrates to developing inflammatory pathologies that associate with Alzheimer's disease (AD). Periodontal disease is a risk factor for cardiovascular disorders (CVD), type II diabetes mellitus (T2DM), AD and other chronic diseases, whilst T2DM exacerbates periodontitis. This study analyzed the relationship between the P. gingivalis/host interactome and the genes identified in genome-wide association studies (GWAS) for the aforementioned conditions using data from GWASdb (P < 1E-03) and, in some cases, from the NCBI/EBI GWAS database (P < 1E-05). Gene expression data from periodontitis or P. gingivalis microarray was compared to microarray datasets from the AD hippocampus and/or from carotid artery plaques. The results demonstrated that the host genes of the P. gingivalis interactome were significantly enriched in genes deposited in GWASdb genes related to cognitive disorders, AD and dementia, and its co-morbid conditions T2DM, obesity, and CVD. The P. gingivalis/host interactome was also enriched in GWAS genes from the more stringent NCBI-EBI database for AD, atherosclerosis and T2DM. The misregulated genes in periodontitis tissue or P. gingivalis infected macrophages also matched those in the AD hippocampus or atherosclerotic plaques. Together, these data suggest important gene/environment interactions between P. gingivalis and susceptibility genes or gene expression changes in conditions where periodontal disease is a contributory factor.
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Affiliation(s)
| | - James France
- Dementia and Neurodegenerative Diseases Research Group, Faculty of Clinical and Biomedical Sciences, School of Dentistry, University of Central Lancashire, Preston, United Kingdom
| | - StJohn Crean
- Dementia and Neurodegenerative Diseases Research Group, Faculty of Clinical and Biomedical Sciences, School of Dentistry, University of Central Lancashire, Preston, United Kingdom
| | - Sim K Singhrao
- Dementia and Neurodegenerative Diseases Research Group, Faculty of Clinical and Biomedical Sciences, School of Dentistry, University of Central Lancashire, Preston, United Kingdom
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Yoshida A, Sasaki H, Toyama T, Araki M, Fujioka J, Tsukiyama K, Hamada N, Yoshino F. Antimicrobial effect of blue light using Porphyromonas gingivalis pigment. Sci Rep 2017; 7:5225. [PMID: 28701797 PMCID: PMC5507902 DOI: 10.1038/s41598-017-05706-1] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2017] [Accepted: 06/09/2017] [Indexed: 01/07/2023] Open
Abstract
The development of antibiotics cannot keep up with the speed of resistance acquired by microorganisms. Recently, the development of antimicrobial photodynamic therapy (aPDT) has been a necessary antimicrobial strategy against antibiotic resistance. Among the wide variety of bacteria found in the oral flora, Porphyromonas gingivalis (P. gingivalis) is one of the etiological agents of periodontal disease. aPDT has been studied for periodontal disease, but has risks of cytotoxicity to normal stained tissue. In this study, we performed aPDT using protoporphyrin IX (PpIX), an intracellular pigment of P. gingivalis, without an external photosensitizer. We confirmed singlet oxygen generation by PpIX in a blue-light irradiation intensity-dependent manner. We discovered that blue-light irradiation on P. gingivalis is potentially bactericidal. The sterilization mechanism seems to be oxidative DNA damage in bacterial cells. Although it is said that no resistant bacteria will emerge using aPDT, the conventional method relies on an added photosensitizer dye. PpIX in P. gingivalis is used in energy production, so aPDT applied to PpIX of P. gingivalis should limit the appearance of resistant bacteria. This approach not only has potential as an effective treatment for new periodontal diseases, but also offers potential antibacterial treatment for multiple drug resistant bacteria.
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Affiliation(s)
- Ayaka Yoshida
- Division of Photomedical Dentistry, Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa, 238-8580, Japan
| | - Haruka Sasaki
- Division of Microbiology, Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa, 238-8580, Japan
| | - Toshizo Toyama
- Division of Microbiology, Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa, 238-8580, Japan
| | - Mitsunori Araki
- Department of Chemistry, Faculty of Science Division I, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo, 162-8601, Japan
| | - Jun Fujioka
- Department of Chemistry, Faculty of Science Division I, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo, 162-8601, Japan
| | - Koichi Tsukiyama
- Department of Chemistry, Faculty of Science Division I, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo, 162-8601, Japan
| | - Nobushiro Hamada
- Division of Microbiology, Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa, 238-8580, Japan
| | - Fumihiko Yoshino
- Division of Photomedical Dentistry, Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa, 238-8580, Japan.
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Ogino T, Ueda T, Ogami K, Koike T, Sakurai K. Effects of chewing rate and reactive hyperemia on blood flow in denture-supporting mucosa during simulated chewing. J Prosthodont Res 2017; 61:54-60. [DOI: 10.1016/j.jpor.2016.04.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2015] [Revised: 03/25/2016] [Accepted: 04/02/2016] [Indexed: 10/21/2022]
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Knight ET, Liu J, Seymour GJ, Faggion CM, Cullinan MP. Risk factors that may modify the innate and adaptive immune responses in periodontal diseases. Periodontol 2000 2016; 71:22-51. [DOI: 10.1111/prd.12110] [Citation(s) in RCA: 91] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/16/2015] [Indexed: 12/31/2022]
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Shimizu Y, Sato S. In vitro study on regeneration of periodontal tissue microvasculature using human dedifferentiated fat cells. J Periodontol 2016; 86:129-36. [PMID: 25102139 DOI: 10.1902/jop.2014.140045] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
BACKGROUND Human dedifferentiated fat cells (HDFATs) may be a new cell type suitable for regenerative therapies. The aim of this study is to assess the potential of HDFATs for vascular regeneration of periodontal tissue. To do this, HDFATs and human gingival endothelial cells (HGECs) were cocultivated, and vascular regeneration was examined in vitro. METHODS HDFATs were isolated from subcutaneous adipose tissue, and HGECs were isolated from gingival cells using anti-cluster of differentiation 31 antibody-coated magnetic beads. HDFATs were cocultured with HGECs in microvascular endothelial cell growth medium-2 (EGM-2MV) for 7 days. Expression of endothelial cell (EC) markers, the formation of capillary-like tubes, and the expression of pericyte markers were determined. RESULTS HDFATs, cultured in EGM-2MV or cocultured with HGECs, expressed EC markers. HDFATs in both conditions initiated tube formation within 5 hours of seeding and formed extensive capillary-like structures within 12 hours. These structures disintegrated within 24 hours when cells were cultured in EGM-2MV alone, whereas cocultured HDFATs maintained tubes for >24 hours. Cocultured HDFATs significantly increased expression of pericyte markers, a cell type associated with microvasculature. CONCLUSION HDFATs possess the ability to express EC markers, and coculture with HGECs promotes differentiation into pericytes involved in the maturation and stabilization of the microvasculature.
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Affiliation(s)
- Yutaka Shimizu
- Department of Periodontology, The Nippon Dental University School of Life Dentistry at Niigata, Niigata, Japan
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30
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Funaki S, Tokutomi F, Wada-Takahashi S, Yoshino F, Yoshida A, Maehata Y, Miyamoto C, Toyama T, Sato T, Hamada N, Lee MCI, Takahashi SS. Porphyromonas gingivalis infection modifies oral microcirculation and aortic vascular function in the stroke-prone spontaneously hypertensive rat (SHRSP). Microb Pathog 2016; 92:36-42. [DOI: 10.1016/j.micpath.2015.12.009] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2015] [Revised: 12/15/2015] [Accepted: 12/22/2015] [Indexed: 02/03/2023]
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Gurav AN. Management of diabolical diabetes mellitus and periodontitis nexus: Are we doing enough? World J Diabetes 2016; 7:50-66. [PMID: 26962409 PMCID: PMC4766246 DOI: 10.4239/wjd.v7.i4.50] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/10/2015] [Revised: 10/16/2015] [Accepted: 01/19/2016] [Indexed: 02/05/2023] Open
Abstract
Periodontitis is the commonest oral disease affecting population worldwide. This disease is notorious for the devastation of tooth supporting structures, ensuing in the loss of dentition. The etiology for this disease is bacterial biofilm, which accumulates on the teeth as dental plaque. In addition to the biofilm microorganisms, other factors such as environmental, systemic and genetic are also responsible in progression of periodontitis. Diabetes mellitus (DM) is metabolic disorder which has an impact on the global health. DM plays a crucial role in the pathogenesis of periodontitis. Periodontitis is declared as the “sixth” major complication of DM. Evidence based literature has depicted an enhanced incidence and severity of periodontitis in subjects with DM. A “two way” relationship has been purported between periodontitis and DM. Mutual management of both conditions is necessary. Periodontal therapy (PT) may assist to diminish the progression of DM and improve glycemic control. Various advanced technological facilities may be utilized for the purpose of patient education and disease management. The present paper clarifies the etio-pathogenesis of periodontitis, establishing it as a complication of DM and elaborating the various mechanisms involved in the pathogenesis. The role of PT in amelioration of DM and application of digital communication will be discussed. Overall, it is judicious to create an increased patient cognizance of the periodontitis-DM relationship. Conjunctive efforts must be undertaken by the medical and oral health care professionals for the management of periodontitis affected DM patients.
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Matsuo M, Okudera T, Takahashi SS, Wada-Takahashi S, Maeda S, Iimura A. Microcirculation alterations in experimentally induced gingivitis in dogs. Anat Sci Int 2016; 92:112-117. [PMID: 26830431 DOI: 10.1007/s12565-015-0324-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2015] [Accepted: 12/18/2015] [Indexed: 11/24/2022]
Abstract
The present study aimed to morphologically examine the gingival microvascular network using a microvascular resin cast (MRC) technique, and to investigate how inflammatory disease functionally affects gingival microcirculation using laser Doppler flowmetry (LDF). We used four beagle dogs with healthy periodontal tissue as experimental animals. To cause periodontal inflammation, dental floss was placed around the cervical neck portions of the right premolars. The unmanipulated left premolars served as controls, and received plaque control every 7 days. After 90 days, gingivitis was induced in the experimental side, while the control side maintained healthy gingiva. To perform morphological examinations, we used an MRC method involving the injection of low-viscosity synthetic resin into the blood vessels, leading to peripheral soft-tissue dissolution and permitting observation of the bone, teeth, and vascular cast. Gingival blood flow was estimated using an LDF meter. The control gingival vasculature showed hairpin-loop-like networks along the tooth surface. The blood vessels had diameters of 20-40 μm and were regularly arranged around the cervical portion. On the other hand, the vasculature in the experimental group was twisted and gathered into spiral forms, with blood vessels that had uneven surfaces and smaller diameters of 8-10 μm. LDF revealed reduced gingival blood flow in the group with experimentally induced gingivitis compared to controls. The actual measurements of gingival blood flow by LDF were in agreement with the alterations that would be expected based on the gingivitis-induced morphological alterations observed with the MRC technique.
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Affiliation(s)
- Masato Matsuo
- Division of Dental Anatomy, Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa, 238-8580, Japan.
| | - Toshimitsu Okudera
- Division of Dental Anatomy, Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa, 238-8580, Japan
| | - Shun-Suke Takahashi
- Division of Circulation Control for Dentistry, Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa, 238-8580, Japan
| | - Satoko Wada-Takahashi
- Division of Circulation Control for Dentistry, Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa, 238-8580, Japan
| | - Shingo Maeda
- Division of Dental Anatomy, Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa, 238-8580, Japan
| | - Akira Iimura
- Division of Dental Anatomy, Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa, 238-8580, Japan
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Saita M, Kaneko J, Sato T, Takahashi SS, Wada-Takahashi S, Kawamata R, Sakurai T, Lee MCI, Hamada N, Kimoto K, Nagasaki Y. Novel antioxidative nanotherapeutics in a rat periodontitis model: Reactive oxygen species scavenging by redox injectable gel suppresses alveolar bone resorption. Biomaterials 2016; 76:292-301. [DOI: 10.1016/j.biomaterials.2015.10.077] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2015] [Revised: 10/26/2015] [Accepted: 10/29/2015] [Indexed: 01/12/2023]
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Tanaka Y, Toyama T, Wada-Takahashi S, Sasaki H, Miyamoto C, Maehata Y, Yoshino F, Yoshida A, Takahashi SS, Watanabe K, Lee MCI, Todoki K, Hamada N. Protective effects of (6R)-5,6,7,8-tetrahydro-l-biopterin on local ischemia/reperfusion-induced suppression of reactive hyperemia in rat gingiva. J Clin Biochem Nutr 2015; 58:69-75. [PMID: 26798200 PMCID: PMC4706094 DOI: 10.3164/jcbn.15-69] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2015] [Accepted: 08/10/2015] [Indexed: 12/20/2022] Open
Abstract
We herein investigated the regulatory mechanism in the circulation responsible for rat gingival reactive hyperemia (RH) associated with ischemia/reperfusion (I/R). RH was analyzed using a laser Doppler flowmeter. RH and I/R were elicited by gingival compression and release with a laser Doppler probe. RH increased in a time-dependent manner when the duration of compression was between 30 s and 20 min. This increase was significantly suppressed by Nω-nitro-l-arginine-methyl-ester (l-NAME), 7-nitroindazole (7-NI), and 2,4-diamino-6-hydroxypyrimidine (DAHP). However, RH was markedly inhibited following 60 min of compression. This inhibition was significantly decreased by treatments with superoxide dismutase (SOD), (6R)-5,6,7,8-tetrahydro-l-biopterin (BH4), and sepiapterin. The luminescent intensity of superoxide anion (O2•−)-induced 2-methyl-6-(4-methoxyphenyl)-3,7-dihydroimidazo-[1,2-a] pyrazine-3-one (MCLA) was markedly decreased by SOD and BH4, but only slightly by sepiapterin. BH4 significantly decreased O2•− scavenging activity in a time-dependent manner. These results suggested that nitric oxide (NO) secreted by the nitrergic nerve played a role in regulating local circulation in rat gingiva. This NO-related regulation of local circulation was temporarily inhibited in the gingiva by the I/R treatment. The decrease observed in the production of NO, which was caused by suppression of NO synthase (NOS) activity subsequent to depletion of the NOS co-factor BH4 by O2•−, played a partial role in this inhibition.
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Affiliation(s)
- Yusaku Tanaka
- Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Toshizo Toyama
- Division of Microbiology, Department of Infection Control, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Satoko Wada-Takahashi
- Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Haruka Sasaki
- Division of Microbiology, Department of Infection Control, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Chihiro Miyamoto
- Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Yojiro Maehata
- Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Fumihiko Yoshino
- Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Ayaka Yoshida
- Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Shun-Suke Takahashi
- Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Kiyoko Watanabe
- Division of Microbiology, Department of Infection Control, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Masaichi-Chang-Il Lee
- Yokosuka-Shonan Disaster Health Emergency Research Center & ESR Laboratories, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Kazuo Todoki
- Department of Health Science, School of Nursing, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Nobushiro Hamada
- Division of Microbiology, Department of Infection Control, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-cho, Yokosuka, Kanagawa 238-8580, Japan
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Muniz FWMG, Nogueira SB, Mendes FLV, Rösing CK, Moreira MMSM, de Andrade GM, Carvalho RDS. The impact of antioxidant agents complimentary to periodontal therapy on oxidative stress and periodontal outcomes: A systematic review. Arch Oral Biol 2015; 60:1203-14. [DOI: 10.1016/j.archoralbio.2015.05.007] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2015] [Revised: 05/18/2015] [Accepted: 05/19/2015] [Indexed: 11/29/2022]
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Gangula P, Ravella K, Chukkapalli S, Rivera M, Srinivasan S, Hale A, Channon K, Southerland J, Kesavalu L. Polybacterial Periodontal Pathogens Alter Vascular and Gut BH4/nNOS/NRF2-Phase II Enzyme Expression. PLoS One 2015; 10:e0129885. [PMID: 26111153 PMCID: PMC4482323 DOI: 10.1371/journal.pone.0129885] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2015] [Accepted: 05/14/2015] [Indexed: 02/06/2023] Open
Abstract
Periodontal disease is a highly prevalent chronic inflammatory disease and is associated with complex microbial infection in the subgingival cavity. Recently, American Heart Association supported a century old association between periodontal disease and atherosclerotic vascular disease. We have recently shown that polybacterial periodontal infection led to aortic atherosclerosis and modulation of lipid profiles; however the underlying mechanism(s) has not been yet demonstrated. Altered nitric oxide (NO) synthesis and tetrahydrobiopterin (BH4), a cofactor for nitric oxide synthases (NOS) has long been shown to be associated with vascular dysfunction and gastrointestinal motility disorders. We sought to examine the mechanism of periodontal infection leading to altered vascular and gastrointestinal smooth muscle relaxation, focusing on the BH4/nNOS pathways. In addition, we also have investigated how the antioxidant system (NRF2-Phase II enzyme expression) in vascular and GI specimens is altered by oral infection. Eight week old male ApoEnull mice were either sham-infected or infected orally for 16 weeks with a mixture of major periodontal bacteria Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia to induce experimental periodontitis. Serum, vascular (mesenteric), stomach, and colon specimens were collected at the end of periodontal pathogen infection. Bacterial infection induced significant (p<0.05) reductions in the levels of BH4,in ratio of BH4:BH2+B and also in nitric oxide levels compared to sham-infected controls. In addition, we identified a significant (p<0.05) reduction in eNOS dimerization, nNOS dimerization and protein expression of BH4 biosynthesis enzymes; GCH-1, DHFR and NRF2 & Phase II enzymes in infected mice versus controls in both mesenteric artery and colon tissues. However, we found no differences in nNOS/BH4 protein expression in stomach tissues of infected and sham-infected mice. This suggests that a polybacterial infection can cause significant changes in the vascular and colonic BH4/nNOS/NRF2 pathways which might lead to impaired vascular relaxation and colonic motility.
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Affiliation(s)
- Pandu Gangula
- Department of Physiology, Meharry Medical College, Nashville, TN, United States of America
- School of Dentistry, Meharry Medical College, Nashville, TN, United States of America
| | - Kalpana Ravella
- Department of Physiology, Meharry Medical College, Nashville, TN, United States of America
| | - Sasanka Chukkapalli
- Department of Periodontology, College of Dentistry, University of Florida, Gainesville, Florida, United States of America
| | - Mercedes Rivera
- Department of Periodontology, College of Dentistry, University of Florida, Gainesville, Florida, United States of America
| | - Shanthi Srinivasan
- Department of Medicine, Division of Digestive Diseases, Emory University, Atlanta, Georgia, United States of America
| | - Ashley Hale
- Department of Cardiovascular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
| | - Keith Channon
- Department of Cardiovascular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom
| | - Janet Southerland
- School of Dentistry, Meharry Medical College, Nashville, TN, United States of America
| | - Lakshmyya Kesavalu
- Department of Periodontology, College of Dentistry, University of Florida, Gainesville, Florida, United States of America
- Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, Florida, United States of America
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Tokutomi F, Wada-Takahashi S, Sugiyama S, Toyama T, Sato T, Hamada N, Tsukinoki K, Takahashi SS, Lee MCI. Porphyromonas gingivalis-induced alveolar bone loss is accelerated in the stroke-prone spontaneously hypertensive rat. Arch Oral Biol 2015; 60:911-8. [DOI: 10.1016/j.archoralbio.2015.02.012] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2014] [Revised: 11/27/2014] [Accepted: 02/13/2015] [Indexed: 02/05/2023]
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Shimada S, Todoki K, Omori Y, Toyama T, Matsuo M, Wada-Takahashi S, Takahashi SS, Lee MCI. Contribution of nitrergic nerve in canine gingival reactive hyperemia. J Clin Biochem Nutr 2015; 56:98-104. [PMID: 25759514 PMCID: PMC4345180 DOI: 10.3164/jcbn.14-71] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2014] [Accepted: 08/19/2014] [Indexed: 11/22/2022] Open
Abstract
Reactive hyperemia reflects a compensatory vasodilation response of the local vasculature in ischemic tissue. The purpose of this study is to clarify the mechanism of regulation of this response in gingival circulation by using pharmacological analysis of reactive hyperemia and histochemical analysis of gingival tissue. Application of pressure to the gingiva was used to create temporary ischemia, and gingival blood flow was measured after pressure release. Reactive hyperemia increased in proportion to the duration of pressure. Systemic hemodynamics remained unaffected by the stimulus; therefore, the gingival reactive hyperemia reflected a local adjustment in circulation. Gingival reactive hyperemia was significantly suppressed by nitric oxide (NO) synthase inhibitors, especially the neural NO synthase-selective antagonist 7-nitroindazole, but not by anticholinergic drugs, β-blockers, or antihistaminergic drugs. Moreover, immunohistochemical staining for neural NO synthase and histochemical staining for NADPH diaphorase activity were both positive in the gingival perivascular region. These histochemical and pharmacological analyses show that reactive hyperemia following pressure release is mediated by NO-induced vasodilation. Furthermore, histochemical analysis strongly suggests that NO originates from nitrergic nerves. Therefore, NO may play an important role in the neural regulation of local circulation in gingival tissue ischemia.
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Affiliation(s)
- Shigeru Shimada
- Department of Oral Science, Kanagawa Dental University, 82 Inaoka-Cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Kazuo Todoki
- Department of Nursing, Junior College, Kanagawa Dental University, 82 Inaoka-Cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Yoichi Omori
- Department of Oral Science, Kanagawa Dental University, 82 Inaoka-Cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Toshizo Toyama
- Department of Infection Control, Division of Microbiology, Kanagawa Dental University, 82 Inaoka-Cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Masato Matsuo
- Department of Tissue-Engineering, Institute for Frontier Oral Science, Kanagawa Dental University, 82 Inaoka-Cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Satoko Wada-Takahashi
- Department of Oral Science, Kanagawa Dental University, 82 Inaoka-Cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Shun-Suke Takahashi
- Department of Oral Science, Kanagawa Dental University, 82 Inaoka-Cho, Yokosuka, Kanagawa 238-8580, Japan
| | - Masaichi-Chang-Il Lee
- Yokosuka-Shonan Disaster Health Emergency Research Center & ESR Laboratories, Graduate School of Dentistry, Kanagawa Dental University, 82 Inaoka-Cho, Yokosuka, Kanagawa 238-8580, Japan
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Peer A, Khamaisi M. Diabetes as a risk factor for medication-related osteonecrosis of the jaw. J Dent Res 2014; 94:252-60. [PMID: 25477311 DOI: 10.1177/0022034514560768] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Medication-related osteonecrosis of the jaw (MRONJ) is a severe devastating complication for which the exact pathogenesis is not completely understood. Multiple systemic and local factors may contribute to the development of MRONJ. A growing body of evidence supports diabetes mellitus (DM) as an important risk factor for this complication; however, the exact mechanism by which DM may promote MRONJ has yet to be determined. The current review elucidates the role of DM in the pathogenesis of MRONJ and the mechanisms by which DM may increase the risk for MRONJ. Factors related to DM pathogenesis and treatment may contribute to poor bone quality through multiple damaged pathways, including microvascular ischemia, endothelial cell dysfunction, reduced remodeling of bone, and increased apoptosis of osteoblasts and osteocytes. In addition, DM induces changes in immune cell function and promotes inflammation. This increases the risk for chronic infection in the settings of cancer and its treatment, as well as antiresorptive medication exposure, thus raising the risk of developing MRONJ. A genetic predisposition for MRONJ, coupled with CYP 450 gene alterations, has been suggested to affect the degradation of medications for DM such as thiazolidinediones and may further increase the risk for MRONJ.
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Affiliation(s)
- A Peer
- Department of Oncology, Rambam Medical Center, Technion, Haifa, Israel
| | - M Khamaisi
- Institute of Endocrinology, Diabetes & Metabolism and Department of Internal Medicine C, Rambam Medical Center & RB Rappaport Faculty of Medicine, Technion, Haifa, Israel
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Lee MCI. [Oxidative stress and periodontal disease--periodontal disease as a life-related disease and vascular disease]. Nihon Yakurigaku Zasshi 2014; 144:281-286. [PMID: 25492364 DOI: 10.1254/fpj.144.281] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/04/2023]
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Comparative analysis of the blood flow values of patients with type 2 diabetes mellitus presenting with chronic periodontitis, patients with chronic periodontitis only and healthy individuals. W INDIAN MED J 2014; 63:359-63. [PMID: 25429482 DOI: 10.7727/wimj.2013.174] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2013] [Accepted: 10/29/2013] [Indexed: 11/18/2022]
Abstract
OBJECTIVES Laser Doppler flowmetry (LDF) is a non-invasive technique used for various reasons in medicine and dentistry. There are many reports of vascular and microcirculatory changes in patients with diabetes mellitus. The aim of the study was to assess the gingival blood flow (GBF) measurements in patients with chronic periodontitis (Group 1), patients with chronic periodontitis and Type 2 diabetes mellitus (Group 2) and healthy controls (Group 3). METHODS Forty-eight individuals were included in the study and divided into three groups. Gingival blood flow measurements were taken from 16 points in the upper vestibular aspect of six anterior teeth using LDF probe. In addition, plaque index (PI), gingival index (GI), probing depth (PD) and attachment loss (AL) were registered to determine the periodontal status. RESULTS Results showed a significant correlation (p < 0.05) in clinical indices and GBF among the groups. Moreover, in Group 1, there was a correlation between GI and AL and between PD and AL. In Group 2, a correlation was observed between PI and AL and between GI and GBF. CONCLUSION The results revealed an increase in GBF value in the chronic periodontitis group with Type 2 diabetes mellitus compared with the group with chronic periodontitis only. Diabetes can also affect GBF due to the nature of the disease, which affects the microcirculatory status.
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Mizuno M, Miyazawa K, Tabuchi M, Tanaka M, Yoshizako M, Yamane C, Torii Y, Maeda H, Goto S. A New Experimental Mouse Model of Periodontitis Using an Orthodontic Ligature Wire. J HARD TISSUE BIOL 2014. [DOI: 10.2485/jhtb.23.255] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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Alteration of the redox state with reactive oxygen species for 5-fluorouracil-induced oral mucositis in hamsters. PLoS One 2013; 8:e82834. [PMID: 24376587 PMCID: PMC3869731 DOI: 10.1371/journal.pone.0082834] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2013] [Accepted: 10/29/2013] [Indexed: 01/27/2023] Open
Abstract
Oral mucositis is often induced in patients receiving cancer chemotherapy treatment. It has been reported that oral mucositis can reduce quality of life, as well as increasing the incidence of mortality. The participation of reactive oxygen species (ROS) in the pathogenesis of oral mucositis is well known, but no report has actually demonstrated the presence of ROS. Thus, the purpose of this study was thus to demonstrate the involvement of ROS and the alteration of the redox state in oral mucositis using an in vivo L-band electron spin resonance (ESR) technique. An oral mucositis animal model induced by treatment of 5-fluorouracil with 10% acetic acid in hamster cheek pouch was used. Lipid peroxidation was measured as the level of malondialdehyde determined by the thiobarbituric acid reaction. The rate constants of the signal decay of nitroxyl compounds using in vivo L-band ESR were calculated from the signal decay curves. Firstly, we established the oral mucositis animal model induced by treatment of 5-fluorouracil with acetic acid in hamster cheek pouch. An increased level of lipid peroxidation in oral mucositis was found by measuring malondialdehyde using isolated hamster cheek pouch ulcer. In addition, as a result of in vivo L-band ESR measurements using our model animals, the decay rate constants of carbamoyl-PROXYL, which is a reagent for detecting the redox balance in tissue, were decreased. These results suggest that a redox imbalance might occur by excessive generation of ROS at an early stage of oral mucositis and the consumption of large quantities of antioxidants including glutathione in the locality of oral mucositis. These findings support the presence of ROS involved in the pathogenesis of oral mucositis with anti-cancer therapy, and is useful for the development of novel therapies drugs for oral mucositis.
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Chandra RV, Srinivas G, Reddy AA, Reddy BH, Reddy C, Nagarajan S, Naveen A. Locally delivered antioxidant gel as an adjunct to nonsurgical therapy improves measures of oxidative stress and periodontal disease. J Periodontal Implant Sci 2013; 43:121-9. [PMID: 23837126 PMCID: PMC3701833 DOI: 10.5051/jpis.2013.43.3.121] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2013] [Accepted: 06/04/2013] [Indexed: 12/14/2022] Open
Abstract
Purpose The present study has two aims; firstly, it attempts to verify the presence of oxidative stress by estimating the reactive oxygen species (ROS) levels in periodontal pockets ≥5 mm as compared to controls. The second aim is to evaluate the effect of lycopene as a locally delivered antioxidant gel on periodontal health and on the gingival crevicular fluid (GCF) levels of 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative injury. Methods Thirty-one subjects participated in this study. In the pretreatment phase, the ROS levels in pockets ≥5 mm were measured by flow cytometry. Three sites in each subject were randomly assigned into each of the following experimental groups: sham group, only scaling and root planing (SRP) was done; placebo group, local delivery of placebo gel after SRP; and lycopene group, local delivery of lycopene gel after SRP. Clinical parameters included recording site-specific measures of GCF 8-OHdG, plaque, gingivitis, probing depth, and clinical attachment level. Results The gel, when delivered to the sites with oxidative stress, was effective in increasing clinical attachment and in reducing gingival inflammation, probing depth, and 8-OHdG levels as compared to the placebo and sham sites. Conclusions From this trial conducted over a period of 6 months, it was found that locally delivered lycopene seems to be effective in reducing the measures of oxidative stress and periodontal disease.
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