Periodontitis is one of the most prevalent bacterial diseases affecting man with up to 90% of the global population affected. Its severe form can lead to the tooth loss in 10-15% of the population worldwide. The disease is caused by a dysbiosis of the local microbiota and one organism that contributes to this alteration in the bacterial population is Prophyromonas gingivalis. This organism possesses a range of virulence factors that appear to contribute to its growth and survival at a periodontal site amongst which is its ability to invade oral epithelial cells. Such an invasion strategy provides a means of evasion of host defence mechanisms, persistence at a site and the opportunity for dissemination to other sites in the mouth. However, previous studies have demonstrated that invasion of the mammalian cells in a population by P. gingivalis is heterogenous, with some cells becoming heavily invaded while others harbour no or only a few bacteria. An understanding of this heterogeneity may throw light on the mechanisms involved and we hypothesised that the phase of the host cell cycle may explain this phenomenon. In an attempt to study the factors influencing P. gingivalis invasion and the cell response to that invasion, a standard antibiotic protection assay was employed and an oral keratinocyte cell line, H357. The results showed that P. gingivalis NCTC 11834 invasion was significantly increased with increasing time of exposure to the cells and the cell density. This may reflect an increased host cell surface area available for bacterial attachment. No effect on invasion of P. gingivalis invasion was observed by the bacterial growth phase, H357 cell passage number or whether cells were pre-incubated with P. gingivalis lipopolysaccharide. Epithelial cells did, however, respond to the presence of P. gingivalis in a number of ways. For example, the mRNA expression of endothelin-1 and urokinase receptor were upregulated with increasing P. gingivalis infection time, suggesting that these proteins could act as inflammatory mediators and possibly as useful markers of the severity of periodontal disease or in the diagnosis and treatment of periodontitis. iii Secondly, in an attempt to investigate the reason for the observed heterogeneous P. gingivalis invasion of H357 cell populations, the effect of cell cycle phase on P. gingivalis invasion was investigated. H357 cells were synchronized by serum starvation. On re-introduction of serum, characterisation of cell cycle phase distribution was performed by flow cytometry following staining with propidium idodide (PI) or by immunofluorescence using bromodeoxyuridine (BrdU), which specifically identifies cells in S-phase. The effect of cell cycle phases on P. gingivalis invasion was measured using the antibiotic protection assay, immunofluorescence and flow cytometry and these were correlated with gene and surface expression of the urokinase receptor and the α5-integrin subunit, which is thought to mediate P. gingivalis invasion. Results showed that the percentage invasion was enhanced with increasing serum re-introduction time, and positively correlated with the number of cells in S-phase. In addition, flow cytometry data showed that the highest association of fluorescent P. gingivalis was with PI positive S-phase cells. Moreover, BrdU positive S-phase cells were 3 times more likely to be invaded and contained 10 times more P. gingivalis than cells in other phases. Also, α5-integrin was more highly expressed in cells in S-phase than other phases, which could explain the mechanism underlying this enhanced invasion. Data presented here have suggested that P. gingivalis targeting of cells in S- phase could, in vivo, allow preferential invasion of the junctional epithelial cells which turns over rapidly. The data presented in this thesis suggest that P. gingivalis invasion is greatly dependent on several factors attributed to the host, the bacteria itself, and to the environment which the bacteria reside in. The invasion occurs within a population of host cells in a heterogeneous fashion, and is dependent on the cell cycle phase, specifically S-phase. This novel finding, in addition to the previously reported mechanisms of P. gingivalis invasion, increases our understanding of this virulence trait and suggests that such a strategy is a highly organised process which the bacteria can follow to ensure its survival within the host. Furthermore, knowledge of these mechanisms could provide novel approaches to treatment of periodontal diseases.
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One of the key molecules in the conversion of sphingosine to sphingosine-1- phosphate is SPHK-1, also known as Sphingosine Kinase 1 (SPHK-1). Sphingosine-1-phosphate (S1P) is a lipid that acts as a signaling molecule and plays an essential role in inflammatory and immunomodulatory responses. S1P has recently been identified as a mediator and a biomarker in inflammatory bone diseases such as osteoporosis and inflammatory osteolysis based on the biological effects of S1P in osteoclastic and osteoblastic cells and immune cells. According to recent research, S1P may play a role in the pathogenesis of periodontitis, an inflammatory bone-destructive condition. This study assesses the salivary level SPHK-1 in periodontitis and its correlat
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Background: Pregnancy is a stressful state of increased inflammatory activity, and pregnancy – associated hormone changes can influence periodontal tissues, these inflammatory activity lead to production of inflammatory mediators. Interleukin 1 beta (IL-1β) is a potent pro-inflammatory cytokines that is consistently associated with periodontal diseases. This study was designed to determine the periodontal health status and detect the serum level of IL-1β in the healthy pregnant women at first, second and third trimester and compare it with healthy non pregnant women, and determine its correlation with different clinical periodontal parameters. M
... Show MoreThe oral cavity has the second major and most diverse microflora after the gut. Since it is the starting point of digestion; the oral microbiota is essential for maintaining oral and systemic health. Thus, this study aimed to find the bacterial isolates which act as a causative agent of periodontal diseases in Iraqi patients and their relation with some immune oral parameters. Saliva specimens and oral swabs of 91 patients (51) and control individuals (40) were collected in this study. The specimens of patients were collected from Al-Amirya and Almaamon Specialized Dental Centers in Baghdad for a period from November/2021 to February/2022. The microbiological results revealed, that the most prevalent bacterial isolates we
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ZM Al-Bahrani, Medico Legal Update, 2021
The systemic and resistant nature of metastatic castration-resistant prostate cancers (mCRPC) renders it largely incurable even after intensive multimodal therapy. Proliferation, survival, and epithelial-mesenchymal transition (EMT) are three fundamental events that are deeply linked to carcinogenesis. Hence, it is necessary to find a new combination of several therapies, targeting those vital mechanisms without causing side effects. Significant research works have shown differential low expression of the metabolic Farnesoid X receptor (FXR) in primary and metastatic prostate cancer suggesting their importance in prostate pathogenesis. Obticholic acid (INT 747), a potent FXR agonist is widely used in primary biliary chola
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Objective To investigate the accuracy of gingival crevicular fluid (GCF) E-cadherin and total antioxidant capacity (TAC) to discriminate periodontal health from disease. Subjects and Methods GCF samples were collected from participants with periodontal health (control), gingivitis, and periodontitis (n = 25 each group). The latter group was further subdivided according to stage (S) and grade. Periodontal parameters were recorded then levels of biomarkers were assayed using ELISA and antioxidant status by use of the Total Antioxidant Capacity Assay for E-cadherin and TAC, respectively. Results All periodontal parameters were significantly higher in periodontally diseased groups than controls. The GCF E-cadherin significantly increased
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This growing interest of the international scientific specialized commissions is due to the role that the audit committee can play, as one of companies’ governance tools, to increase the accuracy and transparency of the financial information disclosed by the companies, through its oversight role on the process of preparing financial reports, its supervision on the internal audit function within the companies, and supporting its independency, as well as coordinating the efforts between the internal control unites and the external auditor represented by the (Board of Supreme Audit) to clear the observations and irregularities in order to reduce the fraud cases.
This research was built on an applied sample of audit committee works
... Show MoreBackground: Relapse of previously moved teeth, is major clinical problem in orthodontics with respect to the goals of successful treatment. This study investigated the effect of orthodontic relapse on the proliferation of fibroblast and epithelial rests of Malassez cells in periodontal ligament of rat molars. Materials and Methods: Sixteen ten-week- old male Wister rats were randomly divided into four groups composed of four animals each: Group I received no orthodontic force (control). In both Group II and Group III, uniform standardized expansive springs were used for moving the maxillary first molars buccally for periods of one and three weeks respectively. The spring initially generated an average expansive force of 20 g on each side.
... Show MoreRheumatoid arthritis and periodontitis use analogous effector destructive procedures, in that the inflammatory cells and pro-inflammatory cytokines that drive chronic bone erosion in RA and chronic periodontal destruction in Periodontitis are alike. Periodontitis (PD) has appeared as a hazard factor in a number of health situations as rheumatoid arthritis (RA). To determine the effect of anti-tumor necrosis factor alpha biological treatment (methotrexate and Enbrel or infliximab) on periodontal status of patients having rheumatoid arthritis with periodontitis in comparison to those having periodontitis without rheumatoid arthritis and control healthy subjects and to determine the serum levels of anti-cyclic citrullinated peptide (ACCP) in t
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