Chronic Periodontal Inflammation Research Articles

Cellular senescence: A new perspective on the suppression of periodontitis (Review).

Cellular senescence, characterized by cell cycle arrest, can result in tissue dysfunction when senescent cells persist and accumulate. Periodontitis, a chronic inflammatory condition caused by the interaction between bacteria and the immune system of the host, primarily manifests as damage to periodontal tissues. Aging and inflammation are interlinked processes that exacerbate each other. The progression of localized chronic periodontal inflammation is often accelerated in conjunction with tissue and organ aging. The presence of senescent cells and release of inflammatory cytokines, immune modulators, growth factors and proteases that are associated with the senescence‑associated secretory phenotype contribute to the deterioration of periodontal tissues. The present review aimed to elucidate the mechanisms of cellular senescence and its potential impact on periodontitis, offering novel insights for modulating the inflammatory microenvironment of periodontal tissues.

Role of Nonalcoholic Fatty Liver Disease in Periodontitis: A Bidirectional Relationship.

Nonalcoholic fatty liver disease (NAFLD) and periodontitis share common risk factors such as obesity, insulin resistance (IR), and dyslipidemia, which contribute to systemic inflammation. It has been suggested that a bidirectional relationship exists between NAFLD and periodontitis, indicating that one condition may exacerbate the other. NAFLD is characterized by excessive fat deposition in the liver and is associated with low-grade chronic inflammation. There are several risk factors for the development of NAFLD, including gender, geriatric community, race, ethnicity, poor sleep quality and sleep deprivation, physical activity, nutritional status, dysbiosis gut microbiota, increased oxidative stress, overweight, obesity, higher body mass index (BMI), IR, type 2 diabetes mellitus(T2DM), metabolic syndrome (MetS), dyslipidemia (hypercholesterolemia), and sarcopenia (decreased skeletal muscle mass). This systemic inflammation can contribute to the progression of periodontitis by impairing immune responses and exacerbating the inflammatory processes in the periodontal tissues. Furthermore, individuals with NAFLD often exhibit altered lipid metabolism, which may affect oral microbiota composition, leading to dysbiosis and increased susceptibility to periodontal disease. Conversely, periodontitis has been linked to the progression of NAFLD through mechanisms involving systemic inflammation and oxidative stress. Chronic periodontal inflammation can release pro-inflammatory cytokines and bacterial toxins into the bloodstream, contributing to liver inflammation and exacerbating hepatic steatosis. Moreover, periodontitis-induced oxidative stress may promote hepatic lipid accumulation and IR, further aggravating NAFLD. The interplay between NAFLD and periodontitis underscores the importance of comprehensive management strategies targeting both conditions. Lifestyle modifications such as regular exercise, a healthy diet, and proper oral hygiene practices are crucial for preventing and managing these interconnected diseases. Additionally, interdisciplinary collaboration between hepatologists and periodontists is essential for optimizing patient care and improving outcomes in individuals with NAFLD and periodontitis.

Blood count, endocrine, immunologic, renal, and hepatic markers in a case-control animal study of induced periodontitis in female rodents.

Introduction: Periodontitis is a non-communicable chronic inflammatory disease with a systemic burden. Animal models of induced periodontitis help elucidate the mechanisms by which periodontal inflammation drives systemic effects. Studying this systemic involvement over longer follow-up periods may provide a strong foundation for future research on the association between diseases and periodontitis, particularly in female rats. Therefore, we aimed to compare blood, endocrine, immunologic, renal, and hepatic markers in a rat model of induced periodontitis in females with their control counterparts. Methods: Experimental periodontitis was induced in 20 female Wistar rats by the application and maintenance of silk ligatures on the upper molars. The rats were then assessed for macroscopical analysis, complete blood count, and biochemical, endocrine, and immunologic markers at 21, 28, 42, and 56days. Results: Chronic periodontal inflammation was observed after 42days of exposure to the ligatures. Additionally, it was also possible to notice significant systemic manifestations, such as the reduction of triiodothyronine and thyroxine levels, along with an increase in the expression of alkaline phosphatase, gamma-glutamyl transpeptidase, and lactate dehydrogenase. Discussion: The study's findings imply that certain changes can be underscored to highlight a reduced risk of conception. Notably, previous investigations have indicated that subfertile women exhibit lower levels of thyroid hormones and elevated lactate dehydrogenase expression. Despite the absence of preclinical data delineating a possible association between periodontitis and female infertility, the results of this study may prove to be a crucial contribution to both the scientific and medical fields.

The Role of Inflammatory Biomarkers of Crevicular Fluid Involved in Modulating of Immune Protection Mechanisms in Chronic Periodontitis

INTRODUCTION: Chronic periodontal inflammation is provoked by persistence of subgingival bacterial flora and is mediated through the production of proinflammatory cytokines that induce the innate immune reactions.
 АIM: To establish the interrelation of secretion of interleukin 1 and immune component of soluble CD14 co-receptor with the main periodontopathogenic microorganisms in patients with chronic generalized periodontitis.
 MATERIALS AND METHODS: A clinical and laboratory examination of patients with chronic generalized periodontitis (n = 100) and individuals with the intact parodontium (n = 63) was conducted. Molecular genetic studies (isolation of periodontal pathogens by polymerase chain reaction in real time), immune enzyme assay (isolation of interleukin 1 and soluble CD14 co-receptor) and statistical analysis of the data obtained were performed.
 RESULTS: The frequency of isolation of periodontopathogenic bacteria in patients with the diagnosis of chronic periodontitis was 96.4% (T. forsythia 81%, р 0.001; P. gingivalis 69%, р 0.001; Tr. denticola 63%, р = 0.054). In 25% of cases, C. Albicans (р 0.001), in 37% Pr. intermedia (р 0.001) and in 30% A. actinomycetemcomitans (р 0.001) were isolated. The average concentrations of soluble CD14 co-receptor were 2.13 [1.89; 2.76] pg/ml in the control group and 20.3 [17.3; 22.5] ng/ml in the group of patients with chronic periodontitis (р 0.001). Concentrations of interleukin 1 were 3.187 [2.356; 4.633] pg/ml in the control group and 33.68 [17.255; 56.915] pg/ml in the group of patients with chronic periodontitis (р 0.001).
 CONCLUSION: Inflammation of periodontal tissues is supported by the factors of aggression and toxins not only of known periodontal pathogens, but also by their associations, which leads to enhancement of virulence factors and increase in secretion of interleukin 1 and soluble CD14 co-receptor, which, in turn, causes destruction of alveolar bone.

THE PROLIFERATIVE ACTIVITY OF FIBROBLASTS OF GINGIVA IN ADULTS AT CHRONIC PERIODONTITIS

Periodontitis is a disease that progresses with age and contributes to the biological aging of the dentition. One of the reasons for this phenomenon is the aging of human gum fibroblasts. Low-intensity laser therapy stimulates the release of growth factors from fibroblasts and their division. The aim of the study was to determine the number, proliferative activity and apoptosis of gingival fibroblasts in people without signs of periodontal inflammation, with chronic periodontitis and after laser therapy. We used biopsy material obtained for periodontal, surgical, orthopedic and orthodontic indications under infiltration anesthesia in two age groups of patients aged 20–40 and 41–60 years. Cell markers Ki-67 and p53 were detected by immunohistochemical methods, the total number of gingival fibroblasts was estimated by staining with hematoxylin and eosin. The results of the conducted studies showed that the number of fibroblasts in the connective tissue lamina of the gums has age-related features. In young people from 20 to 40 years, the number of fibroblasts in gum preparations is 1,12 times higher than in people aged 41–60 years. Among the reasons for the decrease in the number of gingival fibroblasts is a decrease in their proliferative activity and activation of the proapoptotic p53 protein with age. Chronic periodontal inflammation leads to a significant increase in the number of fibroblasts, regardless of the age of the subjects. Fibroblast proliferation and p53 protein expression were more sensitive to microbial inflammation in patients aged 41 to 60 years compared to younger patients. Three-fold laser exposure had a differentiated modulating effect on the state of the gingival fibroblast population, depending on the age of the patients, the number of gingival fibroblasts was restored to the levels characteristic of healthy people, and this was observed only in the group of young patients. Thus, the number of fibroblasts in the human gingival connective tissue lamina changes with age, under conditions of inflammation and under the influence of a diode laser, which must be taken into account in dental practice.

Functional Dentition, Chronic Periodontal Disease and Frailty in Older Adults—A Narrative Review

The likelihood of experiencing the impact of chronic disease rises with age, and cumulative functional deficits over time increase the risk of frailty in older adults. The exact causes of frailty are not clear, and research is needed to identify appropriate intervention measures to reduce risk of developing frailty in old age. To review the evidence on the relationship between frailty, dental status and chronic periodontitis and to determine if improvements in oral health of older adults can contribute to reversal of frailty. The oral cavity is the entry point to the gastro-intestinal tract, and natural teeth facilitate efficient mastication of food prior to swallowing and subsequent digestion. The loss of natural teeth, which is gradual and cumulative over the life course, is associated with diminished nutritional intake, especially in older adults. Furthermore, chronic periodontitis has been postulated as a risk factor for frailty. The evidence supporting a strong relationship between oral health status and frailty is not clearcut. Cross sectional studies suggest an association with missing teeth and chronic periodontal inflammation. However, there are very few longitudinal studies and accordingly, it is not currently possible to claim a causal relationship. As yet, there is no evidence to suggest that improvements in oral health contribute to reversal of frailty. Longitudinal studies with robust designs are required to better inform the relationship across functional dentition, chronic periodontitis and frailty in older adults.

Diagnostic significance of TLR2 and TLR4 receptors on lymphoid cells as a marker of the progression of periodontal inflammation associated with key periodontal pathogenic species <i>F. alocis</i> and <i>P. gingivalis</i>

The aim of the work was to evaluate the diagnostic value of TLR2 and TLR4 expression on periodontal and peripheral blood lymphoid cells by immunofluorescence microscopy in patients with chronic periodontitis associated with key periodontal pathogenic species Filifactor alocis, Porphyromonas gingivalis.
 Materials and methods. The study included 150 patients 88 (59%) women and 62 (41%) men aged 18 to 73 years with chronic periodontitis in the acute phase (CP) and 32 people without signs of chronic periodontal inflammation. To confirm the diagnosis of periodontitis, the Multident-5 PCR kit was used (detection of P. gingivalis, Prevotella intermedia, Tannerella forsythia, Treponema denticola, Aggregatibacter actinomycetemcomitans), as well as rt-PCR for F. alocis and P. gingivalis in the contents of the periodontal pocket (NPF GenLab, Russia). To evaluate cells carrying CD282 and CD284 markers, gingival fluid flushes from the periodontal pocket with Hanks' solution were used. The isolated cells were stained with antibodies to CD282 markers (corresponding to TLR2 receptor) or CD284 (corresponding to TLR4 receptor) labeled with FITC, and fixed with paraformaldehyde for subsequent immunofluorescence microscopy.
 Results. The expression of TLR2 and TLR4 on peripheral blood and gingival fluid leukocytes was studied in individuals with healthy periodontitis and patients with chronic periodontitis associated with F. alocis, P. gingivalis. According to the results of PCR, the detection rate of F. alocis and P. gingivalis was 64 and 62.7%, respectively, which confirmed their dominance in the microbial association. It was found that the expression of TLR2 and TLR4 on peripheral blood lymphoid cells varied in humans. The possible diagnostic significance of this phenomenon in assessing the progression of chronic periodontitis is discussed.
 Conclusion. In patients with chronic periodontitis associated with the dominance of periodontopathogenic species F. alocis, P. gingivalis, the multidirectional expression of TLR2 and TLR4 on peripheral blood cells was observed, which may have diagnostic significance in assessing the progression of periodontal diseases.

Periodontal status in patients with Alzheimer’s disease: a scoping review

Periodontitis is the most common condition of chronic periodontal infection and inflammation in the elderly population. Periodontal disease can cause local inflammation that contributes to higher risk of systemic inflammatory disease. Current research suggests a possible link between periodontal disease and neurodegenerative disease, such as Alzheimer’s disease. The aim of the study is to provide a profile of the periodontal tissue status in people with Alzheimer’s disease. This scoping review followed Joanna Briggs Institute (JBI) guideline, and the searching was conducted using PubMed, Cochrane, and EBSCOHost databases during February 6th – February 7th, 2021 with keywords of periodontal disease, periodontitis, periodontal inflammation, Alzheimer’s disease and dementia. It also included MeSH terms of “periodontal disease” and “Alzheimer’s disease” if available. Additionally, snowballing technique was used to include more articles. The identification and writing process for this article followed the PRISMA-ScR framework. There were 60 articles included in this study. This scoping review shows a profile of general characteristics including decreased oral hygiene and periodontal tissue status showed by high score of plaque and calculus, gingival inflammation, high percentage of Clinical Attachment Loss (CAL), Bleeding on Probing (BOP) along with deterioration of cognitive function. There was a decreasing level of periodontal health along with the decline in cognitive function experienced by AD participants. However, further research is needed to see the mechanism of this relationship.

STUDY OF THE INFLUENCE OF BACTERIAL LYSATE ON INDICATORS OF LYSOSOMAL PHOSPHATASE ACTIVITY IN EXPERIMENTAL PERIODONTITIS IN RATS

Introduction. One of the stages of the pathophysiological study of the parameters of mineral metabolism of alkaline (ALP) and acidic (AP) phosphatases – enzymes of bone tissue of osteoblast and osteoblast membranes in experimental periodontitis against the background of the use of bacterial lysate Respibron® was carried out. Materials and methods. Experimental periodontitis in rats was in the modification of O.I. Sukmansky. There were rats with experimental periodontitis and rats treated by Respibron (10 mg/kg 1 time per day) or Imudon for 30 days. Determination of alkaline (ALP) and acidic (AP) phosphatases activity (pH 4.8 and 10.5) was performed according to the methodological recommendations of AP Levitsky et al. Discussion of results. It was found that by the end of the 90-day period of the experiment, a statistically stable course of chronic damage to the periodontium was observed in terms of ALP and AP, which exceeded the intact ones by 1.93 and 1.4 times, respectively, which reflects the hypoergic state of chronic periodontal inflammation. A powerful corrective effect of the drugs Respibron® and Imudon® on markers of osteoblast and osteoblast activity in experimental periodontitis has been proven. Established a stimulating effect on osteoregeneration Respibron® in the hypoergic course of the inflammatory process. The therapeutic effect of Respibron® is more expressive and powerful compared to Imudon®. Conclusions.The results obtained make it possible to continue the study of the course of experimental periodontitis in order to establish the mechanisms of development, protection, and restoration of tissues under the conditions of the pharmacological correction Respibron®.

STUDY OF THE INFLUENCE OF BACTERIAL LYSATE ON INDICATORS OF LYSOSOMAL PHOSPHATASE ACTIVITY IN EXPERIMENTAL PERIODONTITIS IN RATS

Introduction. One of the stages of the pathophysiological study of the parameters of mineral metabolism of alkaline (ALP) and acidic (AP) phosphatases – enzymes of bone tissue of osteoblast and osteoblast membranes in experimental periodontitis against the background of the use of bacterial lysate Respibron® was carried out. Materials and methods. Experimental periodontitis in rats was in the modification of O.I. Sukmansky. There were rats with experimental periodontitis and rats treated by Respibron (10 mg/kg 1 time per day) or Imudon for 30 days. Determination of alkaline (ALP) and acidic (AP) phosphatases activity (pH 4.8 and 10.5) was performed according to the methodological recommendations of AP Levitsky et al. Discussion of results. It was found that by the end of the 90-day period of the experiment, a statistically stable course of chronic damage to the periodontium was observed in terms of ALP and AP, which exceeded the intact ones by 1.93 and 1.4 times, respectively, which reflects the hypoergic state of chronic periodontal inflammation. A powerful corrective effect of the drugs Respibron® and Imudon® on markers of osteoblast and osteoblast activity in experimental periodontitis has been proven. Established a stimulating effect on osteoregeneration Respibron® in the hypoergic course of the inflammatory process. The therapeutic effect of Respibron® is more expressive and powerful compared to Imudon®. Conclusions.The results obtained make it possible to continue the study of the course of experimental periodontitis in order to establish the mechanisms of development, protection, and restoration of tissues under the conditions of the pharmacological correction Respibron®.

Maintaining homeostatic control of periodontal bone tissue.

Alveolar bone is a unique osseous tissue due to the proximity of dental plaque biofilms. Periodontal health and homeostasis are mediated by a balanced host immune response to these polymicrobial biofilms. Dysbiotic shifts within dental plaque biofilms can drive a proinflammatory immune response state in the periodontal epithelial and gingival connective tissues, which leads to paracrine signaling to subjacent bone cells. Sustained chronic periodontal inflammation disrupts "coupled" osteoclast-osteoblast actions, which ultimately result in alveolar bone destruction. This chapter will provide an overview of alveolar bone physiology and will highlight why the oral microbiota is a critical regulator of alveolar bone remodeling. The ecology of dental plaque biofilms will be discussed in the context that periodontitis is a polymicrobial disruption of host homeostasis. The pathogenesis of periodontal bone loss will be explained from both a historical and current perspective, providing the opportunity to revisit the role of fibrosis in alveolar bone destruction. Periodontal immune cell interactions with bone cells will be reviewed based on our current understanding of osteoimmunological mechanisms influencing alveolar bone remodeling. Lastly, probiotic and prebiotic interventions in the oral microbiota will be evaluated as potential noninvasive therapies to support alveolar bone homeostasis and prevent periodontal bone loss.

Omega-3 Polyunsaturated Fatty Acids EPA and DHA as an Adjunct to Non-Surgical Treatment of Periodontitis: A Randomized Clinical Trial.

Periodontitis is a chronic multifactorial inflammatory disease that leads to the loss of supportive tissues around the teeth with gradual deterioration of masticatory function and esthetics, resulting eventually in the decrease of the life quality. Host immune response triggered by bacterial biofilm is responsible for the chronic periodontal inflammation and ongoing tissue loss. Omega-3 polyunsaturated fatty acids (PUFA) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anti-inflammatory properties, thus may be used for the treatment of chronic inflammatory diseases. In this study, we aimed to evaluate the effect of dietary supplementation with omega-3 PUFA in the patients with stage III and IV periodontitis. Thirty otherwise healthy patients were treated with scaling and root planning (SRP). In the test group (n = 16), patients were additionally supplemented with 2.6 g of EPA and 1.8 g of DHA. In the control group (n = 14), patients received only SRP. Periodontal examination was performed at baseline and three months following initial therapy. Salivary samples were taken twice at baseline and at the end of the experiment. We found that there was a statistically significant reduction in the bleeding on probing (BOP) and improvement of clinical attachment loss (CAL) at three months in the test group compared to the control group. Moreover, a statistically significant higher percentage of closed pockets (probing depth ≤ 4 mm without BOP) was achieved in the test group vs. control group after three months of treatment. Accordingly, the levels of pro-inflammatory cytokines/chemokines interleukin (IL)-8 and IL-17 were markedly lower, while the level of anti-inflammatory IL-10 was significantly higher in the salivary samples of the patients supplemented with omega-3 PUFA at three months in comparison to the patients treated with SRP alone. Our findings demonstrate that dietary intervention with high-dose of omega-3 PUFA during non-surgical therapy may have potential benefits in the management of periodontitis.

Expression of human and Porphyromonas gingivalis glutaminyl cyclases in periodontitis and rheumatoid arthritis–A pilot study

ObjectivesHuman glutaminyl cyclases (QC and isoQC) play an important role in maintaining inflammatory conditions. Meanwhile a glutaminyl cyclase synthesized by Porphyromonas gingivalis (PgQC), a key pathogen in developing periodontitis and a potential link of periodontitis with rheumatoid arthritis (RA), was discovered. This study was aimed to determine the expression of QC, isoQC and PgQC in patients with chronic periodontitis (CP) and RA. DesignThirty volunteers were enrolled in a pilot study and divided into 3 groups (healthy, CP and RA individuals). Blood samples, biofilm and gingival crevicular fluid (GCF) were analysed for mRNA expression of QC, isoQC and P. gingivalis QC. Major bacteria being associated with periodontal disease were quantified in subgingival biofilm and protein levels for monocyte chemoattractant protein (MCP)-1, MCP-3 and interleukin (IL)-1β) were determined in the GCF. Expression of PgQC on the mRNA and protein levels was assessed in two P. gingivalis strains. ResultsPgQC is expressed in P. gingivalis strains and the protein seems to be located mainly in peri-plasmatic space. mRNA expression of QC was significantly increased in the peripheral blood from RA patients vs. healthy subjects and CP patients (p = 0.013 and p = 0.003, respectively). In GCF of RA patients, QC mRNA was detected more frequently than in healthy controls (p = 0.043). In these samples IL-1β levels were also elevated compared to GCF from periodontally healthy individuals (p = 0.003). PgQC was detected in eight out of the 13 P. gingivalis positive biofilm samples. ConclusionActivity of QC may play a supportive role in maintaining chronic periodontal inflammation and destruction in RA. PgQC is expressed in vivo but further research is needed to evaluate biological importance of this enzyme and if it constitutes a potential target in periodontal antimicrobial therapy.

Association of Elevated C-Reactive Protein with Severe Periodontitis in Hypertensive Patients in Lagos, Nigeria: A Pilot Study.

Background:Epidemiological studies have shown that individuals with chronic periodontitis have a significantly higher risk of developing cardiovascular complications, which might be attributed to the increased production of inflammatory cytokines initiated by the complex microbiota in dental biofilm.Aim:The study aims to evaluate the association between chronic periodontitis and C-reactive protein (CRP) levels in a group of hypertensive individuals in Nigeria.Materials and Methods:The investigator enrolled 50 hypertensive patients with chronic periodontitis into the study from the medical outpatient clinic of a teaching hospital in Lagos, Nigeria. Full-mouth periodontal examination was done to assess the participant's periodontal status, with probing depths and clinical attachment levels of six sites on all teeth. The investigator defined periodontitis as at least one interproximal site with probing depth ≥4 mm. Classification of participants into three groups was done based on their severity of periodontitis; mild (n = 16), moderate (n = 27), and severe (n = 7) periodontitis. Their CRP serum levels were measured, and the association with the severity of periodontitis was determined. P was found to be ≤ 0.05.Results:The median CRP levels were 1.0 (0.6, 2.2), 2.4 (1.1, 4.8), and 4.1 mg/L (3.3, 9.4) for mild, moderate, and severe chronic periodontitis, respectively. The association between the serum CRP levels and severity of periodontitis was statistically significant (P = 0.006).Conclusion:There was an association of elevated serum CRP level with increased severity of chronic periodontitis in hypertensive individuals. This preliminary finding among Nigerians suggests that chronic periodontal inflammation may contribute to systemic inflammatory burden in hypertensive patients.

歯科における炭酸ガスレーザー

Currently,the carbon dioxide gas laser approved in the dental field is only at the wavelength of 10,600 nm. The application to the actual oral cavity condition can be applied to the actual oral pathology by abscess incision, chronic periodontal inflammation, evaporation for aesthetic improvement of pigmented gingiva, frenectomy, tumor resection, secondary surgery after implantation of dental implant, gingival fenestration of difficulty eruptive tooth, application to stomatitis, gingivectomy, evaporation of defective granulation tissue, evaporation of inflammatory edematous gingival hyperplasia tissue, treatment for hypersensitivity of teeth. Some of them are introduced.

Potential anti-inflammatory activity of selected plants from Asteraceae family in in vitro models

Plants from the Asteraceae family are traditionally used for treating inflammation-associated diseases, such as atherosclerosis, diabetes mellitus, bowel diseases (IBD; Crohn's disease and ulcerative colitis), asthma, chronic obstructive pulmonary disease (COPD), skin diseases and periodontal inflammation [1]. These diseases are closely associated with an excessive inflammatory response of stimulated neutrophils [2]. That is why selected extracts were examined for their effect on pro-inflammatory functions of stimulated neutrophils such as: reactive oxygen species (ROS), interleukin 8 (IL-8), tumor necrosis factor alpha (TNFα) and adhesion molecules.

Chronic Inflammation and Carcinogenesis – Emerging Role of Chronic Inflammatory Periodontal Disease

With exponential increase in the number of cases of cancers worldwide in recent past, it is imperative to enhance our understanding about the etiologic and risk factors associated with this seriously morbid condition. Increasing attention has been focussed on chronic infections and inflammatory diseases, implicating a role in carcinogenesis, particularly in developing countries. Periodontal disease is a bacterially induced chronic inflammatory process that affects tooth supporting connective tissue and alveolar bone in the oral cavity, potentially leading to tooth loss. The concept of these diseases as localized entities affecting only the teeth and supporting apparatus has been revised lately, in the light of mounting evidence of periodontal infection’s influence on chronic inflammatory disease states. Periodontal disease has been linked to several systemic conditions like cardiovascular diseases, diabetes mellitus, adverse pregnancy outcomes, obesity and cancers, yet underlying mechanisms are still elucidating. The focus of this review article will be an in depth discussion of the role of chronic inflammation, particularly chronic periodontal inflammation in causation or association of human cancers and discussion of possible biological mechanisms involved.

Inhibition of pre-existing natural periodontitis in non-human primates by a locally administered peptide inhibitor of complement C3.

Human periodontitis is associated with overactivation of complement, which is triggered by different mechanisms converging on C3, the central hub of the system. We assessed whether the C3 inhibitor Cp40 inhibits naturally occurring periodontitis in non-human primates (NHPs). Non-human primates with chronic periodontitis were intra-gingivally injected with Cp40 either once (5 animals) or three times (10 animals) weekly for 6weeks followed by a 6-week follow-up period. Clinical periodontal examinations and collection of gingival crevicular fluid and biopsies of gingiva and bone were performed at baseline and during the study. A one-way repeated-measures anova was used for data analysis. Whether administered once or three times weekly, Cp40 caused a significant reduction in clinical indices that measure periodontal inflammation (gingival index and bleeding on probing), tissue destruction (probing pocket depth and clinical attachment level) or tooth mobility. These clinical changes were associated with significantly reduced levels of pro-inflammatory mediators and decreased numbers of osteoclasts in bone biopsies. The protective effects of Cp40 persisted, albeit at reduced efficacy, for at least 6weeks following drug discontinuation. Cp40 inhibits pre-existing chronic periodontal inflammation and osteoclastogenesis in NHPs, suggesting a novel adjunctive anti-inflammatory therapy for treating human periodontitis.

Cellular microenvironment and collagen destruction during periodont inflammation

Background. The association between periodontitis and collagen damage with immune cells is an actual problem. Periodontitis is a bacterially induced exacerbation of chronic process and chronic inflammatory disease that destroys teeth supporting connective tissue. Bacteria initiate periodontitis and destruction of the alveolar periodontal connective tissue. Objectives. Immune cells location between damaged collagen fibers remains obscure and this is the purpose of the current study. Results. We have determined five variants of immune cells microenvironment: nodular, trabecular, diffuse, mixed. We have observed five types of collagen structures destruction in exacerbation of chronic process and chronic periodontal inflammation. They are characterized by swelling, pulping and insignificant necrosis. Conclusion. Connective tissue has signs of swelling and destruction during inflammation; edema is observed between collagen fibers. Collagen fiber damage during periodontitis is caused by neutrophils. Widespread edema of collagen fibers increasing of depth cells infiltration during chronic inflammation. Nodular type of immune cells microenvironment is observed during outcome of chronic inflammation. Trabecular type of immune cells microenvironment is observed during exacerbation of chronic process. Diffuse type of immune cells microenvironment is observed during chronic inflammation process.

Rac-Null Leukocytes Are Associated with Increased Inflammation-Mediated Alveolar Bone Loss

Periodontitis is characterized by altered host-biofilm interactions that result in irreversible inflammation-mediated alveolar bone loss. Genetic and epigenetic factors that predispose to ineffective control of biofilm composition and maintenance of tissue homeostasis are not fully understood. We elucidated how leukocytes affect the course of periodontitis in Rac-null mice. Mouse models of acute gingivitis and periodontitis were used to assess the early inflammatory response and patterns of chronicity leading to loss of alveolar bone due to inflammation in Rac-null mice. Leukocyte margination was differentially impaired in these mice during attachment in conditional Rac1-null (granulocyte/monocyte lineage) mice and during rolling and attachment in Rac2-null (all blood cells) mice. Inflammatory responses to subgingival ligatures, assessed by changes in peripheral blood differential leukocyte numbers, were altered in Rac-null compared with wild-type mice. In response to persistent subgingival ligature-mediated challenge, Rac-null mice had increased loss of alveolar bone with patterns of resorption characteristic of aggressive forms of periodontitis. These findings were partially explained by higher osteoclastic coverage of the bone-periodontal ligament interface in Rac-null compared with wild-type mice. In conclusion, this study demonstrates that leukocyte defects, such asdecreased endothelial margination and tissue recruitment, are rate-limiting steps in the periodontal inflammatory process that lead to more aggressive forms of periodontitis.