Endocannabinoid system and periodontitis: mechanisms and therapeutic implications / Sistema endocanabinoide e periodontite: mecanismos e implicações terapêuticas

Introdução: A periodontite é um importante problema de saúde pública. Embora o princípio da terapia da periodontite esteja focado principalmente na remoção do biofilme dental e dos fatores associados, sua fisiopatologia registra diferentes eventos moleculares e inflamatórios relacionados ao sistema imunológico do hospedeiro, como a participação do sistema endocanabinoide. Objetivo: Esta revisão teve como objetivo explorar e elucidar os mecanismos e papéis do sistema endocanabinoide na fisiopatologia da periodontite e suas possibilidades para futuras terapias relacionadas. Material e método: Realizou-se uma busca eletrônica na plataforma PubMed por estudos envolvendo a ação do sistema endocanabinoide sobre a periodontite. Resultado: Dezenove estudos clínicos e pré-clínicos foram incluídos nesta revisão narrativa. Conclusão: Os receptores canabinoides tipo 1 e 2 são componentes integrais do sistema endocanabinoide e manifestam-se de várias formas nos tecidos periodontais. As ações e mecanismos através dos quais os receptores canabinoides são ativados em locais saudáveis ou inflamados continuam a ser o foco de investigações em curso. Além disso, os fitocanabinoides e canabinoides sintéticos apresentam potencial como tratamentos, com estudos pré-clínicos indicando benefícios na redução da inflamação e na facilitação da reparação dos tecidos.

Introduction: Periodontitis is a major public health problem. Although the principle of periodontitis therapy is mainly focused on removing dental biofilm and associated factors, its physiopathology enrolls different molecular and inflammatory events related to the host immune system, as the participation of the endocannabinoid system. Objective: This review aimed to explore and elucidate the mechanisms and roles of the endocannabinoid system on periodontitis physiopathology and its possibilities for future related therapies. Material and method: An electronic search was carried out on the PubMed platform for studies involving the action of the endocannabinoid system on periodontitis. Result: Nineteen clinical and preclinical studies were included in this narrative review. Conclusion: Cannabinoid receptors type 1 and 2 are integral components of the endocannabinoid system, manifesting in various forms in the periodontal tissues. The actions and mechanisms through which cannabinoid receptors are activated in healthy or inflamed sites remain the focus of ongoing investigations. Moreover, phytocannabinoids and synthetic cannabinoids show therapeutic potential, with pre-clinical studies indicating benefits in reducing inflammation and facilitating tissue repair

Lactobacillus helveticus Prevents Periodontitis Induced by Aggregatibacter actinomycetemcomitans in Rats by Regulating ß-Defensins.

Objective: To study the preventive effect of Lactobacillus helveticus (L. helveticus) on periodontitis induced by Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) in rats. Methods: Eighteen 8-week-old female rats were randomly divided into three groups: Sham group, Trehalose group, and L. helveticus SBT2171 (LH2171) group. We measured the distance of the cementoenamel junction-alveolar bone crest (CEJ-ABC) to evaluate alveolar bone resorption. Hematoxylin-eosin staining was used to observe the histopathological changes of rat hemimaxillary tissues. We detected the expression of ß-defensins, tumor necrosis factor-α (TNF-α), interleukin- (IL-) 1ß, and IL-6 and the number of A. actinomycetemcomitans in rat gingival tissues by quantitative reverse transcriptase polymerase chain reaction. The levels of IL-1ß, IL-6, and TNF-α in rat gingival tissues were also measured by enzyme-linked immunosorbent assay. Results: Compared with the Trehalose group, the distance of CEJ-ABC was prominently reduced and alveolar bone resorption was notably improved in the LH2171 group. And the infiltration of inflammatory cells in the hemimaxillary tissue decreased obviously, periodontal fibers were arranged neatly, connective tissue small blood vessels proliferated, and the number of A. actinomycetemcomitans reduced significantly in the LH2171 group. In addition, the mRNA expression and release of inflammatory factors in the gingival tissues in the LH2171 group were notably lower than those in the Trehalose group. On the 21st and 36th day, the expression of ß-defensins in the gingival tissue of the LH2171 group increased significantly. Conclusion: L. helveticus improves alveolar bone resorption and increases the expression of ß-defensins thereby inhibiting the number of A. actinomycetemcomitans and thus prevents periodontitis.

A novel fluorescent probe for detecting hydrogen sulfide in osteoblasts during lipopolysaccharide-mediated inflammation under periodontitis.

Periodontitis, one of the most common chronic inflammatory diseases, affects the quality of life. Osteogenesis plays an important role in the disease. There is a connection between hydrogen sulfide (H2S) and periodontitis, but according to the study has been published, the precise role of H2S in inflammation remains in doubt. The main reason for the lack of research is that H2S is an endogenous gasotransmitter, difficult to discern through testing. So, we synthesized a novel fluorescence probe which can detect H2S in vitro. By using the novel H2S fluorescence probe, we found that H2S changes in osteoblasts mainly by cystathionine-γ-lyase, and H2S increases under LPS stimulation. H2S could be a potential marker for diagnosis of inflammatory diseases of bone, and might help deepen studies of the changes of H2S level and promote the progression on the researches about pathogenesis of periodontitis.

Diabetes Mellitus and Periodontitis Share Intracellular Disorders as the Main Meeting Point.

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.

Association between Periodontitis and Carotid Artery Calcification: A Systematic Review and Meta-Analysis.

Recent studies have supported the relationship between periodontitis and carotid artery calcification (CAC), but still uncertain. This systematic review is aimed at evaluating the association between periodontitis and CAC. The search was conducted in four electronic databases: PubMed, EMBASE, Web of Science, and The Cochrane Library, supplemented by checking references of included articles and related review articles. Eligibility assessment and data extraction were conducted independently. The quality assessment and publication bias analysis were performed. The association between periodontitis and CAC was presented in odd ratio (OR) with 95% confidence interval (CI). Additional outcomes included the percentage of alveolar bone loss in CAC versus non-CAC. Twelve studies were included, and 10 were performed quantity analysis. Periodontitis with secure definition (OR = 2.02, 95%CI = 1.18 - 3.45) and insecure definition (OR = 10.78, 95%CI = 4.41 - 26.34) was associated with CAC. And a higher average percentage of alveolar bone loss (weighted mean difference = 10.84%; 95%CI = 6.40 - 15.48) was also observed in CAC patients compared to non-CAC patients. No significant publication bias was found. The results of this systematic review and meta-analysis revealed a significant relationship between periodontitis and CAC.

Guanabenz inhibits alveolar bone resorption in a rat model of periodontitis.

Increase of sympathetic activity has been known to exacerbate osteoporosis through promotion of bone resorption. However, it is largely unknown about involvement of sympathetic activity in exacerbation of periodontitis. In this study, we investigated whether α2-adrenergic receptor (α2-AR) agonist guanabenz which decreases sympathetic activity, attenuates alveolar bone resorption in rats having high sympathetic activity with periodontitis. Volumes of residual alveolar bone and attachment levels in periodontium were examined using micro-computed tomography and hematoxylin-eosin staining, respectively. Furthermore, osteoclast numbers per bone surface and osteoclast surface per bone surface were measured using tartrate-resistant acid phosphatase staining. To examine the suppressive effects of guanabenz on pro-inflammatory cytokines, expression levels of tyrosine hydroxylase (TH), TNF-α, IL1-ß, and IL-6 in periodontium were measured using immunohistostaining. Administration of guanabenz attenuated loss of alveolar bone and attachment levels in rats having high sympathetic activity. Furthermore, its administration suppressed osteoclast numbers in rats having high sympathetic activity. TH, TNF-α, IL-1ß, and IL-6 positive cells in periodontium in rats treated with guanabenz for 12 weeks, were lower than those in control rats having high sympathetic activity. This study demonstrated administration of α2-AR agonist guanabenz attenuates alveolar bone resorption through decrease of sympathetic activity in rats.

Quercetin Prevents Oxidative Stress-Induced Injury of Periodontal Ligament Cells and Alveolar Bone Loss in Periodontitis.

PURPOSE: Emerging evidence has indicated that oxidative stress (OS) contributes to periodontitis. Periodontal ligament cells (PDLCs) are important for the regeneration of periodontal tissue. Quercetin, which is extracted from fruits and vegetables, has strong antioxidant capabilities. However, whether and how quercetin affects oxidative damage in PDLCs during periodontitis remains unknown. The aim of this study was to assess the effects of quercetin on oxidative damage in PDLCs and alveolar bone loss in periodontitis and underlying mechanisms. MATERIALS AND METHODS: The tissue block culture method was used to extract human PDLCs (hPDLCs). First, a cell counting kit 8 (CCK-8) assay was used to identify the optimal concentrations of hydrogen peroxide (H2O2) and quercetin. Subsequently, a 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA) probe, RT-qPCR, Western blotting and other methods were used to explore the effects of quercetin on OS in hPDLCs and the underlying mechanism. Finally, quercetin was administered to mice with periodontitis through gavage, and the effect of quercetin on the level of OS and alveolar bone resorption in these mice was observed by immunofluorescence, microcomputed tomography (micro-CT), hematoxylin and eosin staining (H&E) staining and so on. RESULTS: Quercetin at 5 µM strongly activated NF-E2-related factor 2 (NRF2) signaling, alleviated oxidative damage and enhanced the antioxidant capacity of hPDLCs. In addition, quercetin reduced cellular senescence and protected the osteogenic ability of hPDLCs. Finally, quercetin activated NRF2 signaling in the periodontal ligaments, reduced the OS level of mice with periodontitis, and slowed the absorption of alveolar bone in vivo. CONCLUSION: Quercetin can increase the antioxidant capacity of PDLCs and reduce OS damage by activating the NRF2 signaling pathway, which alleviates alveolar bone loss in periodontitis.

Periodontal Inflamed Surface Area Mediates the Link between Homocysteine and Blood Pressure.

Here, we assess the association between homocysteine (Hcy) serum levels and periodontal status in a large representative sample of the National Health and Nutrition Examination Survey (NHANES). Using the 2001-2002 and 2003-2004 NHANES databases, participants with a periodontal examination, medical self-reported data, blood pressure (BP) and blood samples to determine complete blood count, C-reactive protein (CRP) and Hcy levels. We then calculated the periodontal inflamed surface area (PISA) and the periodontal epithelial surface area (PESA). Multivariable regression analysis explored the association between Hcy, periodontal measures and BP. Mediation analysis was performed to understand the effect of PISA and PESA in the link between Hcy and BP. 4021 participants fulfilled the inclusion criteria. Hcy levels showed significant correlations with systolic BP, diastolic BP, PISA, PESA and age. PESA showed to be significantly associated with Hcy both for the crude and adjusted models (p < 0.01), but not PISA (p > 0.05). In the association of Hcy with systolic BP, PISA significantly mediated 17.4% and PESA 0.9%. In the association of Hcy with diastolic BP, PISA significantly mediated 16.3% and PESA 47.2%. In conclusion, Hcy and periodontitis are associated. Further, both PISA and PESA significantly mediated the association of Hcy with systolic BP and diastolic BP. Future studies shall deepen the mechanisms by which Hcy levels increase in a clinical situation of periodontitis.

Remote Ischemic Preconditioning Protects Against Endothelial Dysfunction in a Human Model of Systemic Inflammation: A Randomized Clinical Trial.

OBJECTIVE: Inflammation, oxidative stress, and endothelial dysfunction are known to contribute to ischemia-reperfusion injury. Remote ischemic preconditioning (RIPC) protects from endothelial dysfunction and the damage induced by ischemiareperfusion. Using intensive periodontal treatment (IPT), an established human model of acute systemic inflammation, we investigated whether RIPC prevents endothelial dysfunction and modulates systemic levels of inflammation and oxidative stress. APPROACH AND RESULTS: Forty-nine participants with periodontitis were randomly allocated to receive either 3 cycles of ischemia-reperfusion on the upper limb (N=24, RIPC) or a sham procedure (N=25, control) before IPT. Endothelial function assessed by flow-mediated dilatation of the brachial artery, inflammatory cytokines, markers of vascular injury, and oxidative stress were evaluated at baseline, day 1, and day 7 after IPT. Twenty-four hours post-IPT, the RIPC group had lower levels of IL-10 (interleukin-10) and IL-12 (interleukin-12) compared with the control group (P<0.05). RIPC attenuated the IPTinduced increase in IL-1ß (interleukin-1ß), E-selectin, sICAM-3 (soluble intercellular adhesion molecule 3), and sTM (soluble thrombomodulin) levels between the baseline and day 1 (P for interaction <0.1). Conversely, oxidative stress was differentially increased at day1 in the RIPC group compared with the control group (P for interaction <0.1). This was accompanied by a better flow-mediated dilatation (mean difference 1.75% [95% CI, 0.428­3.07], P=0.011). After 7 days from IPT, most of the inflammatory markers, endothelial-dependent and -independent vasodilation, were similar between groups. CONCLUSIONS: RIPC prevented acute endothelial dysfunction by modulation of inflammation and oxidation processes in patients with periodontitis following exposure to an acute inflammatory stimulus. REGISTRATION: URL: https://clinicaltrials.gov/ct2/show/NCT03072342; Unique identifier: NCT03072342.

The Role of Alcohol, LPS Toxicity, and ALDH2 in Dental Bony Defects.

It is estimated that 560 million people carry an East Asian-specific ALDH2*2 dominant-negative mutation which leads to enzyme inactivation. This common ALDH2 polymorphism has a significant association with osteoporosis. We hypothesized that the ALDH2*2 mutation in conjunction with periodontal Porphyromonas gingivalis bacterial infection and alcohol drinking had an inhibitory effect on osteoblasts and bone regeneration. We examined the prospective association of ALDH2 activity with the proliferation and mineralization potential of human osteoblasts in vitro. The ALDH2 knockdown experiments showed that the ALDH2 knockdown osteoblasts lost their proliferation and mineralization capability. To mimic dental bacterial infection, we compared the dental bony defects in wild-type mice and ALDH2*2 knockin mice after injection with purified lipopolysaccharides (LPS), derived from P. gingivalis which is a bacterial species known to cause periodontitis. Micro-computed tomography (micro-CT) scan results indicated that bone regeneration was significantly affected in the ALDH2*2 knockin mice with about 20% more dental bony defects after LPS injection than the wild-type mice. Moreover, the ALDH2*2 knockin mutant mice had decreased osteoblast growth and more dental bone loss in the upper left jaw region after LPS injection. In conclusion, these results indicated that the ALDH2*2 mutation with alcohol drinking and chronic exposure to dental bacterial-derived toxin increased the risk of dental bone loss.

Association between number of teeth and Alzheimer's disease using the National Database of Health Insurance Claims and Specific Health Checkups of Japan.

Associations of numbers of teeth present and of missing teeth with Alzheimer's disease were cross-sectionally analyzed using the National Database of Health Insurance Claims and Specific Health Checkups of Japan. Dental care claims data of patients aged 60 years or older diagnosed with periodontitis (n = 4,009,345) or missing teeth (n = 662,182) were used to obtain information about the numbers of teeth present and of missing teeth, respectively, and they were combined with medical care claims data including the diagnosis of Alzheimer's disease. Numbers of teeth present and of missing teeth excluding third molars were calculated using the dental formula in the claims for periodontitis and missing teeth, respectively, and categorized into three groups each. Percentages of subjects treated for Alzheimer's disease with 20-28, 10-19, and 1-9 teeth present were 1.95%, 3.87%, and 6.86%, respectively, in patients diagnosed as having periodontitis, and those treated for Alzheimer's disease with 1-13, 14-27, and 28 missing teeth were 2.67%, 5.51%, and 8.70%, respectively, in patients diagnosed as having missing teeth. Logistic regression models using treatment for Alzheimer's disease as an outcome variable and adjusting for age and sex showed that odds ratios (95% confidence intervals) for patients with 10-19 and 1-9 teeth (reference: 20-28 teeth) were 1.11 (1.10-1.13) and 1.34 (1.32-1.37), respectively, (p<0.001), in patients diagnosed as having periodontitis, and odds ratios (95% confidence intervals) for patients with 14-27 missing teeth and 28 missing teeth (reference: 1-13 missing teeth) were 1.40 (1.36-1.44) and 1.81 (1.74-1.89), respectively, (p<0.001), in patients diagnosed as having missing teeth. In conclusion, the results of the present study using Japanese dental claims data showed that older people visiting dental offices with fewer teeth present and a greater number of missing teeth are more likely to have Alzheimer's disease.

Association Between Periodontitis and Blood Pressure Highlighted in Systemically Healthy Individuals: Results From a Nested Case-Control Study.

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Adrenal incidentaloma as a novel independent predictive factor for periodontitis.

PURPOSE: There are no data regarding periodontal derangements in patients with adrenal incidentalomas (AI). We assessed the frequency and severity of periodontitis in patients with AI [non-functioning adrenal incidentaloma (NFAI) and possible autonomous cortisol secretion (ACS)] and compared with individuals with normal adrenal. METHODS: A cross-sectional study evaluated thirty-five individuals with AI and 26 controls. NFAI and possible ACS diagnosis was based on the current guidelines: NFAI [cortisol levels after 1 mg dexamethasone suppression test (1 mg-DST) ≤ 1.8 µg/dL (≤ 50 nmol/L)]; possible ACS [cortisol levels after 1 mg-DST 1.9-5.0 µg/dL (51-138 nmol/L)]. Sociodemographic data were collected, and a full-mouth periodontal evaluation was performed. RESULTS: There was no significant difference between groups regarding age, sex, income, ethnicity, education level, smoking, body mass index, dysglycemia, and arterial hypertension. Patients with AI exhibited worse periodontal conditions than controls for the following periodontal clinical parameters: mean percentage of probing pocket depth (PPD) and clinical attachment level (CAL) ≥ 5 mm (p < 0.001 and p = 0.006, respectively). Patients with NFAI and possible ACS showed higher gingival bleeding index (p = 0.014), bleeding on probing (p < 0.001), and CAL (p < 0.001) means compared to controls. The frequencies of periodontitis were 72.7% in patients with NFAI, 84.6% in possible ACS, and 30.8% in controls (p = 0.001). Periodontitis was more severe in patients with possible ACS than NFAI and controls. Patients with NFAI and possible ACS exhibited odds ratio for periodontitis of 4.9 (p = 0.016) and 8.6 (p = 0.02), respectively. CONCLUSION: Patients with AI have higher frequency and severity of periodontitis than controls. The presence of AI was an independent predictive factor for periodontitis.

Asarylaldehyde enhances osteogenic differentiation of human periodontal ligament stem cells through the ERK/p38 MAPK signaling pathway.

Periodontitis is an inflammatory disease that affects tooth-supporting tissues. Chronic inflammation can progress to periodontitis, which results in loss of alveolar bone. Asarylaldehyde is a potential substance for bone metabolism present in natural compounds. Here, we propose the application of asarylaldehyde in the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) to prevent bone loss. We investigated the effect of asarylaldehyde on hPDLSCs together with bone differentiation media in vitro. The osteogenic differentiation effect was observed after treatment of hPDLSCs with several concentrations of asarylaldehyde. After 21 days, osteogenic cells were identified by mineralization. We also observed that asarylaldehyde increased the mRNA expression of osteoblast-specific markers in hPDLSCs. Interestingly, asarylaldehyde regulated the levels of alkaline phosphatase (ALP) transcriptional activity through the p38/extracellular-signal-regulated kinase (ERK) signaling pathway. Notably, asarylaldehyde induced hPDLSCs to promote osteogenic differentiation. These results suggest that asarylaldehyde plays a key role in the osteogenic differentiation of hPDLSCs. Asarylaldehyde may be a good candidate for the application of natural compounds in future in periodontal regeneration.

Effects of periodontitis on postoperative pneumonia in patients with lung and esophageal cancer.

BACKGROUND: Few studies have been conducted on the relationship between chronic periodontitis and postoperative pneumonia (POP) in patients with lung and esophageal cancer. Furthermore, it remains controversial as to whether improving the periodontal condition of patients with lung and esophageal cancer before surgery reduces the incidence of POP. This retrospective study was conducted to assess the effects of periodontal therapy in patients with lung and esophageal cancer to prevent POP. METHODS: A total of 265 patients with lung or esophageal cancer complicated with chronic periodontitis who underwent open thoracotomy between July 2015 and June 2019 were selected and given the choice of being in the experimental or control group. A total of 141 participants in the experimental group received periodontal therapy, and 124 participants in the control group did not receive periodontal therapy. All clinical data of participants in both groups were retrospectively studied to determine the incidence of POP on the 30th day after discharge from hospital. RESULTS: Eight patients in the experimental and six in the control group, respectively, were excluded from the study. It was found that four of the 133 patients suffered from POP in the experimental group (incidence: 3.01%). A total of 18 of 118 patients in the control group had a pulmonary infection (incidence: 15.25%). POP incidence in the experimental group was significantly lower than that in the control group, and in the level analysis of different types of periodontitis, surgical methods, and diseases (p < 0.05). CONCLUSIONS: Periodontal treatment is associated with a lower incidence of POP following lung and esophageal cancer surgery. Improving the periodontal condition of patients helps prevent POP. The presence of periodontitis is an important predisposing factor for POP in patients after open thoracotomy. Periodontal examination and therapy are recommended before the surgical treatment of lung or esophageal cancer.

Baicalein inhibits inflammatory response and promotes osteogenic activity in periodontal ligament cells challenged with lipopolysaccharides.

BACKGROUND: Periodontitis is a chronic infection initiated by oral bacterial and their virulence factors, yet the severity of periodontitis is largely determined by the dysregulated host immuno-inflammatory response. Baicalein is a flavonoid extracted from Scutellaria baicalensis with promising anti-inflammatory properties. This study aims to clarify the anti-inflammatory and osteogenic effects of baicalein in periodontal ligament cells (PDLCs) treated with lipopolysaccharides (LPS). METHODS: Human PDLCs were incubated with baicalein (0-100 µM) for 2 h prior to LPS challenge for 24 h. MTT analysis was adopted to assess the cytoxicity of baicalein. The mRNA and protein expression of inflammatory and osteogenic markers were measured by real-time polymerase chain reaction (PCR), western blot and enzyme-linked immunosorbent assay (ELISA) as appropriate. Alkaline phosphatase (ALP) and Alizarin red S (ARS) staining were performed to evaluate the osteogenic differentiation of PDLCs. The expression of Wnt/ß-catenin and mitogen-activated protein kinase (MAPK) signaling related proteins was assessed by western blot. RESULTS: MTT results showed that baicalein up to 100 µM had no cytotoxicity on PDLCs. Baicalein significantly attenuated the inflammatory factors induced by LPS, including interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), matrix metalloprotein-1 (MMP-1), MMP-2 and monocyte chemoattractant protein 1 (MCP-1) at both mRNA and protein level. Moreover, MAPK signaling (ERK, JNK and p38) was significantly inhibited by baicalein, which may account for the mitigated inflammatory response. Next, we found that baicalein effectively restored the osteogenic differentiation of LPS-treated PDLCs, as shown by the increased ALP and ARS staining. Accordingly, the protein and gene expression of osteogenic markers, namely runt-related transcription factor 2 (RUNX2), collagen-I, and osterix were markedly upregulated. Importantly, baicalein could function as the Wnt/ß-catenin signaling activator, which may lead to the increased osteoblastic differentiation of PDLCs. CONCLUSIONS: With the limitation of the study, we provide in vitro evidence that baicalein ameliorates inflammatory response and restores osteogenesis in PDLCs challenged with LPS, indicating its potential use as the host response modulator for the management of periodontitis.

Effect of periodontal treatment on the glomerular filtration rate, reduction of inflammatory markers and mortality in patients with chronic kidney disease: A systematic review.

AIM: To assess the effect of periodontal treatment (PT) on glomerular filtration rate (GFR), systemic inflammation, or mortality in patients with chronic kidney disease (CKD). METHODS: A literature search was performed on PubMed and Web of Science databases on articles published until December 2019. The PRISMA guidelines were used throughout the manuscript. RESULTS: Of the total studies found, only 18 met the inclusion criteria; four retrospective and 14 prospective studies (including 3 randomized controlled trials-RCT). After PT, 3 studies investigated GFR, 2 found significant improvement; 11 (including 2 RCTs) investigated C-reactive protein levels, 9 found a significant improvement (including the 2 RCTs); 5 (including 3 RCTs) investigated Interleukine-6 level, 4 found a significant improvement (including 2 RCTs) and 2 studies evaluated mortality, one (retrospective study) found a significant difference. CONCLUSIONS: Within the limitations of the present study, PT seems to improve CKD status, especially by reducing the systemic inflammation. Further RCTs are needed to confirm the results and specifically assess the influence of different types of PT in CKD patients. Taking into consideration the ability of PT to prevent further tooth loss and denutrition, early management of periodontitis is extremely important in patients with impaired renal function.

Periodontitis and alzheimer's disease

BACKGROUND: Alzheimer's disease (AD), the main cause of dementia in the adult population, is characterized by a progressive loss of cognitive function. It is considered that neuroinflammation plays a fundamental role in its onset and progression. The bacteria present in the disbiotic microbiome generated during the course of periodontitis (PE) are capable of inducing a systemic inflammatory response, exacerbating the production of proinflammatory mediators that have the potential to spread to the systemic circulation. MATERIAL AND METHODS: A literature review was made using the databases Scielo, PubMed, EBSCO and key words "Alzheimer disease", "Periodontitis", "Neurodegeneration", "Inflammation mediators", "Elderly". RESULTS: Several hypotheses point to similar pathophysiological pathways in the establishment of AD and PE, sharing cellular and molecular proinflammatory characteristics. In periodontitis, locally produced cytokines and pro-inflammatory products spread from the ulcerated periodontal pocket into the systemic circulation, or around the trigeminal nerve terminals, which allows the passage of bacteria or their products to the brain. This fact leads to the formation of plaques of amyloid peptide and intraneuronal neurofibrillar tangles (NFTs) that activate the glial cells producing a significant increase in proinflammatory cytokines in the affected regions that lead to a loss of neuronal synapses and neurodegeneration, contributing to the progression of AD. CONCLUSIONS: This review of the literature contributes to the understanding of the pathological pathways shared by both diseases such as oxidative damage and inflammation. There is not enough evidence to determine an association between this two pathologies, so it is considered necessary to conduct studies for determine if periodontitis is capable of inducing or exacerbating the neuroinflammation that will trigger AD

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Caloric restriction prevents alveolar bone loss in the experimental periodontitis in obese rats.

AIMS: It has been shown that periodontitis, can be modified by systemic changes, including behavioral factors, such as diet. Caloric restriction is one of the dietary therapeutic strategies indicated for obesity. It is associated with several benefits, among them, modulation of the inflammatory response. The aim of this study was to verify whether caloric restriction in obese rats changes the progression of experimental ligature-induced periodontitis. MATERIALS AND METHODS: Forty-eight Wistar rats were used for 24 weeks and initially fed with cafeteria diet during 12 weeks. The animals were divided into four groups according to the caloric restriction and experimental periodontitis. The cotton thread was placed around the mandibular first molars, for 15 days, before the end of the experiment. Rats submitted to caloric restriction received, from the 13th week of the experimental protocol, 70% of the food intake compared to the ad libitum animals of other study of the our research group. Alveolar bone loss was assessed using macroscopic morphometric analysis. Analyzes of clinical periodontal measures, biometrics, serum biomarkers and biochemical parameters were performed. KEY FINDINGS: Caloric restriction decreased the alveolar bone loss in the periodontitis group when compared to the group that received a cafeteria diet with periodontitis. Moreover, the results demonstrate the improvement in the glycemic profile, without prejudice to bone tissue biomarkers. SIGNIFICANCE: Based on the results, caloric restriction reduces the progression of alveolar bone loss in rats with experimental periodontitis, in addition to presenting benefits in biometric data, decreasing both glycemic profile and clinical periodontal measures.

Mandibular biomechanical behavior of rats submitted to chronic intermittent or continuous hypoxia and periodontitis.

BACKGROUND: The aim of this study was to investigate the effects of exposure to continuous (CH) and intermittent (IH) hypoxia on biomechanical properties of the mandible and periodontal tissue of animals submitted to experimental periodontitis (EP) when applying loads in a hypoxic environment. METHODS: Adult female Wistar rats were exposed during 90 days to IH or CH (simulated high altitude of 4200 m above sea level). Fourteen days prior to the euthanasia, EP was induced to half of the animals of each group. RESULTS: Only in the rats with EP, IH decreased the maximum capacity of the mandible to withstand load and the limit of elastic load. Indicators of intrinsic properties of the bone material were significantly reduced by both types of hypoxia in rats with EP. Hypoxia enhanced the alveolar bone loss induced by EP in the buccal side of the mandible, without showing additional effects in lingual or interradicular bone. Hypoxia increased prostaglandin E2 content in gingival tissue of healthy animals and further elevated the E2 levels increased by EP. CONCLUSIONS: When periodontitis is present, hypoxic stress induces a decrease in mineral properties that ultimately affects the ability of the mandible to resist load, mainly during intermittent exposure to hypoxia. These effects on bone may be related to the higher levels of prostaglandin E2 reached in the surrounding gingival tissue. The findings of this study may stimulate strategies to prevent unwanted effects of hypoxia on periodontal tissues.