<p> Background: Corticosteroid medications have been researched extensively in oral surgery procedures for the proposed reduction in trismus, swelling, and pain. No consensus has been determined for the most efficacious type, timing, and dosage of medication thus far. In addition little is known about the usage of corticosteroids for periodontal and implant related procedures. The aims of this review are to help clinicians understand the usage of corticosteroid medications in various dental surgeries.</p><p> Methods: The PubMed-MEDLINE and the Cochrane-CENTRAL databases were searched through and up till June 2015 to identify appropriate studies regarding this aim. Appropriate studies were those reporting on the usage of corticosteroids related to its pathophysiology, surgical related outcomes, and patient related outcomes in dental procedures. Conclusions: The search yielded 256 unique papers after selection resulted in 12 publications that met the eligibility criteria. In general the usage of corticosteroids in third molar extractions improved post operatives outcomes related to edema, trismus, and a slight reduction in pain. However, It cannot be recommended to use corticosteroids for pain management. Due to the various types, routes, and dosages of corticosteroid used in studies, no specific drug, route, or dosage can be recommended by literature. The usage of corticosteroids for periodontal and implant related procedures has not been investigated. Further research is required to investigate the possible benefits of corticosteroids on reduction of surgical swelling in periodontal and implant related surgeries.</p>

Desmosomes and adherens junctions are intercellular junctions crucial for epithelial cell-cell adhesion and maintenance of normal tissue architecture. Desmoglein 3 (Dsg3), a member of the desmoglein sub-family, serves as an adhesion molecule in desmosomes. Its importance in cell-cell adhesion has been highlighted by the autoimmune blistering disease pemphigus vulgaris, where autoimmune antibodies directed against Dsg3 trigger a cascade of intracellular events, resulting in structural defects and blister formation in the skin and oral mucosa. In addition to its adhesive function, Dsg3 is also acknowledged to have other important roles in the regulation of cell proliferation and differentiation. Our group suggested that Dsg3 is involved in the regulation of keratinocyte stem cell differentiation, but the underlying mechanism(s) were unclear (Wan et al, 2003; Wan et al, 2007). We hypothesise that Dsg3 may be involved in the regulation of the E-cadherin-mediated cell adhesion and the reorganisation of actin cytoskeleton, which in turn contributes to differentiation programs and tissue morphogenesis. Thus, the aim of this study was to examine the interactions between Dsg3, E-cadherin and actin and to explore the underlying signalling pathways that are associated with these intercellular junctions. Using both a gain and loss of Dsg3 functional approaches, I demonstrate that Dsg3 is capable of interacting with E-cadherin and involved in the regulation of calcium-induced E-cadherin junction assembly and the activation of Src signalling pathway. Overexpression of Dsg3 increased E-cadherin/Src signalling with enhanced levels of Src and pSrc co-purified with E-cadherin. Knockdown of Dsg3 inhibited this pathway with reversed effect, suggesting that Dsg3 acts as an upstream regulator of Src signalling in the regulation of E-cadherin-mediated adherens junction formation. In addition, I show another novel function of Dsg3 in promoting actin dynamics through regulating Rac1 and Cdc42-GTPase activities, resulting in pronounced membrane protrusions and enhanced rate of actin turnover. Taken together, my work suggests that Dsg3 play an important signalling role in the assembly of E-cadherin-mediated cell adhesion and the dynamic of actin cytoskeleton.

The primary etiologic factor of periodontitis is bacterial plaque biofilm. Nevertheless, the factors that determine the progression of periodontitis are complex and poorly understood. Hence, the potential involvement of autoimmunity in the pathogenesis of periodontitis has been considered intermittently for years. The basic hypothesis for this PhD was that autoimmunity to native and/or posttranslationally modified periodontal extracellular matrix proteins is involved in the progression of periodontitis. Objectives The main objective of the study was to extend the understanding of periodontal disease pathogenesis beyond the common bacterial etiology and to address the hypothesis that periodontal disease is an auto-immune disease. This research will try to identify the exact neoepitope. Specific aims (i). To investigate the involvement of autoimmune reactivity towards native collagen type I (CI) and collagen type III (CIII), as well as CI and CIII posttranslationally modified by reactive oxygen specious (ROS) known to present in the inflamed tissue, ROS-CI and ROS-CIII, respectively. (ii). Develop human antibody fragment(s) specific to CI, ROS-CI, CIII and ROSCIII for diagnostic application. Methods Modification of CI or CIII was confirmed by SGS-PAGE, Capillary Electrophoresis and 3D-fluorescence. The presence of autoantibodies to ROS-CI and ROS-CIII in sera and saliva were then studied by ELISA and Western blotting using sera and saliva from individuals with Aggressive Periodontitis (AgP), Chronic Periodontitis (CP) and Gingivitis (G). Antibodies specific to ROS-CI and ROS-CIII were developed using phage display semi-synthetic human single chain fragment variable (scFv) libraries. Results Autoantibodies to native CI, native CIII, ROS-CI and ROS-CIII were observed exclusively in patients with AgP. Human antibody fragments specific to native and ROS-CI were developed and evaluated. Conclusions A. Autoimmune reactions to native and post-translationally modified self antigens may play a role specifically in the pathogenesis of AgP. B. Anti-ROS scFv specific to ROS-CI and ROS-CIII may have diagnostic future applications.

Aims: To investigate the relationship between oral health and obesity in adolescents attending Public and Private Schools in Sharjah City, United Arab Emirates. Methods: 1094 adolescents attending secondary school in Sharjah City were asked to participate in a randomised cross-sectional study, (QMREC2007/60). Two separate structured questionnaires were used to determine; 1. The demographic details, dietary habits, physical activity and oral hygiene practice from the adolescents and 2. Socio-economic and general health from their guardian. A two part clinical examination i) dental caries (WHO, 1997) and oral cleanliness (Pitts et al., 1997), ii) measurement of height and weight to calculate BMI was also carried out. Data analysis included descriptive, univariate and multiple regressions. Results: Full dataset on 803 adolescents was obtained and used for analysis. The study response rate of 93% resulted in 50 % male, 40% UAE nationals and 66% attending Private school. The mean DMFT was 3.19 (SD 2.9), 25% were caries free, mean BMI was 21 and 15% were obese. A significant association between DMFT and BMI was found (r=0,097, p=0.006), with each extra 10 point in BMI there was a 0.57 increase in DMFT. The DMFT predictive model confirmed significant association of father’s education (p<0.001), gender (p=0.008) and ethnicity (p=0.001). Positive significance of age (p<0.001), consumption of tea with sugar (p=0.024) and soft drinks (p<0.001), whereas three daily meals (p=0.009) and visiting the dentist (p=0.007) were protective. The BMI model confirmed positive significance of age (p<0.001), school fees (p=0.005), obesity in family (p<0.001) and soft drink consumption (p<0.001). Three daily meals (p=0.007) and increased drinking frequency of milk (p=0.026) were found to be protective. Conclusions: Analysis of the final model suggests that there is no clear relationship between obesity and dental caries, but that the consumption of soft drinks was a leading predictor for both diseases (obesity and dental caries).

Background: Oral pain has been reported to prevent successful tobacco cessation in Bangladeshi paan tobacco chewers. Aim: to investigate oral pain associated with paan tobacco chewing cessation. Objectives: to identify and assess the impact and association of predictors of oral pain with paan tobacco cessation. Methods: This prospective cohort study recruited UK resident adult Bangladeshi women. Socio-demographic, social capital, general and oral health condition, tobacco use, dependence and cessation data were analysed in four study groups; 1) oral pain at baseline, 2) continued oral pain 3) onset of oral pain during follow-up and 4) at study completion. Results: 150 participants (mean age 51, range 24-84 years) completed the study. Most (92%) were never employed, had no formal education (59%) and chewed both zarda and tobacco leaf (69%). Participants who chewed more paan tobacco (OR 2.270, 95% CI; 1.980-5.258), were anxious when going without paan tobacco (OR 1.908, 95% CI: 1.728-4.995) with dental calculus (OR 3.350, 95% CI; 1.716-15.680) and no completed formal education (OR 3.349, 95% CI; 1.395-8.039) reported baseline oral pain. Oral debris (OR 3.963, 95% CI; 1.045-15.031) and no completed formal education (OR 2.524, 95% CI; 1.866-7.359) predicted continued oral pain. Successful quitters at study completion (OR 4.213, 95% CI; 1.509-13.863) quitting with behavioural support alone (OR 2.932, 95% CI; 1.635-5.873) with tooth erosion (OR 3.880, 95% CI; 1.248-12.061) predicted onset of oral pain. Successful quitters (OR 2.497, 95% CI: 1.603-3.715) quitting with behavioural support alone (OR 2.139, 95% CI; 1.872-5.248) with filled teeth (OR 3.166, 95% CI; 1.826-12.134), tooth erosion (OR 2.849, 95% CI; 1.029-7.892) and living in a low status neighbourhood (OR 4.551, 95% CI; 1.068-19.398) predicted oral pain at study completion. Conclusions: Predictors of oral pain for all four study groups were multi-factorial, including lifestyle and behavioural factors, tobacco dependence and cessation, sociodemographics and oral clinical condition.

Primary cell culture is limited by the increase in cellular levels of p16INK4a in response to an in vitro culture environment and, in conjunction with telomere shortening following cell division, presents a barrier to cellular proliferation. The use of transformed cell lines is limited for studies wherein the aim is to generate data akin to an in vivo environment as commonly such cell lines achieve their immortal benefits by down regulating important tumour suppressive mechanisms and inhibiting cell cycle checkpoints. Normal Human Oral Keratinocyte (NHOK) cells expressing shp16+hTERT were generated and compared to NHOK cells expressing Bmi1 +hTERT using an optimized retroviral transduction protocol and compared simultaneously to an epidermal control. Population doubling assessment of cell lines revealed that shp16+hTERT was not sufficient to extend replicative lifespan in the absence of p53 whilst cell lifespan extension was observed not only in cells expressing Bmi1+hTERT, but also in cells transduced with Bmi1 alone. Upon characterization, cells showed expression of p53 and responsiveness to UVB-induced apoptosis as demonstrated by an increase in p53 expression. NHOKBmi1+hTERT displayed adaptability to serum free culture when weaned into keratinocyte serum free media (KSFM) and retained the ability to stratify into multiple layers when supported by feeders on polycarbonate membrane inserts. The cell line NHOKBmi1+hTERT will be beneficial for in vitro studies looking to utilise an alternative to transformed or spontaneously derived cell lines and holds potential for further development and optimization into a well characterized SSE in a user friendly, and reproducible system for the testing for oral products.

This thesis aimed to study the inter-relationship between the oral health status, aspects of the adaptive and innate immune response, and the oral microbiome of a well-defined cohort of Behçet’s syndrome (BS) patients. Methods Patients thought to have BS were referred to one of the two centres participating in this study (St Thomas’ Hospital and Royal London Hospital). Diagnosis was based on the International Study Group (ISG) criteria. Information about the frequency of the different symptoms of the disease along with the treatment protocol was collected on a data sheet and stored electronically in a database, in the period between January 2006 and August 2012. The data were then analysed at the end of the study period. The quality of life (QoL) and oral health status of BS patients in the UK was compared to those from Turkey. Furthermore, the oral health status of BS patients in the UK was compared to that of healthy control (HC) volunteers and recurrent aphthous stomatitis (RAS) patients. Saliva and oral swabs were cultured and purified to homogeneity and bacteria were identified by matrix-assisted laser desorption/ionisation-time of flight (MALDI-TOF). Salivary viral load and the serum immunoglobulin (Ig) G of the different herpes viruses were also examined. In order to determine whether there were differences in the innate response efficacy in BS patients, the expression of key molecular determinants of pathogen recognition was also analysed. Total ribonucleic acid (RNA) was purified from non-ulcerated buccal mucosal brush biopsies and analysed by real time polymerase chain reaction (qPCR) for the presence of toll-like receptor (TLR) 2 messenger RNA (mRNA) and TLR4 mRNA, and their splice variants. The functions of TLR2 and TLR4 were also investigated. Results In the investigated cohort of UK BS patients, all patients had a history of recurrent oral ulceration, 85.6% had dermatological lesions, 79.1% had rheumatological manifestations, 73.9% had genital ulceration, 68.6% had ocular involvement, 15% had neurological manifestations, and 10.5% had vascular involvement. The most frequent treatment was colchicine (54.2%), followed by topical corticosteroid therapy (53.6%) then azathioprine (43.8%). The QoL of BS patients from the UK and Turkey was affected to a similar extent. The Turkish BS patients had generally poorer oral health status in comparison to the UK BS patients. Nevertheless, the UK BS patients had also generally poorer oral health status in comparison to HC volunteers. The oral health status of the UK BS patients was comparable to those suffering from RAS. The oral mucosal and salivary microbial profile was variable between individuals in the same group and between individuals in different groups. The orally active BS patients’ oral mucosa showed the highest microbial community complexity and diversity compared to all the other investigated groups. Moreover, the BS patients had statistically higher salivary Epstein-Barr virus (EBV) shedding compared to HC volunteers, but not to RAS patients. Relapsed BS patients’ oral mucosa expressed higher levels of TLR2 and TLR4 mRNA. Investigation of the known splice variants of both receptors revealed that TLR2 mRNA variants b, d and e, and TLR4 variants 3 and 4 are significantly elevated in relapsed BS patients. A significant defect in the response to cognate agonists of TLR1/2 heterodimer and TLR4 was also observed in the whole BS patient cohort. Furthermore, BS patients expressed a lower cytomegalovirus (CMV) IgG level in comparison to all the investigated groups. Conclusion In conclusion, BS patients show higher levels of expression of some of the unusual splice variants of TLR2 and TLR4 mRNA, which might contribute to the observed functional defect in TLR1/2 heterodimer and TLR4. This defect in the key molecular determinants of pathogen recognition can lead to a failure in the adaptive immune responses’ modulation, resulting in the observed decrease in the expression of CMV IgG in BS patients and indeed the increase in susceptibility to oral infections. Furthermore, it is envisaged that the reported discrepancy in the oral microbiome of BS patients can be targeted in the future by probiotics to restore the balance of the oral microbial community, leading to better oral health which in turn will enable a better control of the BS immune response.

South Asians residing in the UK are known to be significantly different in terms of socio-economic and cultural influences from the UK population in general. They are at substantially higher risk of developing oral cancer (OSCC) and the potentially malignant disorder (PMD) oral submucous fibrosis (OSF). To overcome barriers to conventional health service use, a mobile dental unit was the base for screening within the South Asian community. Bilingual advocates ensured cultural acceptability and actively recruited high-risk individuals for screening as well as being involved at the secondary referral centre to facilitate attendance for definitive diagnosis of positive screened individuals. In total 1596 high-risk individuals were screened and 5.4% referred with suspicious lesions. No OSCC was detected in any positive screened individuals but PMDs were confirmed in 29%, with dysplasia (15%) and OSF (9%) the commonest lesions referred. Due to the complex presentation of OSCC the most appropriate gold standard screening outcome is the detection of individuals who cannot be discharged from long-term follow-up at the secondary referral centre. On this basis screening specificity was 99% and Positive Predictive Value (PPV) 79%. The low PPV was attributed to the high prevalence of complex oral mucosal lesions (46%) that cannot be definitively diagnosed as benign by visual examination alone, which indicates diagnostic aids are required for screening this high-risk population. 4 Compliance with referral for positive screened individuals was only 76% and immediate incisional biopsy of positive screened individuals would be needed to improve this. In addition to histological detection of dysplasia, molecular markers of disease could readily be investigated by immunohistochemistry and the expression of keratins are ideal candidates due to their responsiveness to pathological signalling and abnormal expression in oral (pre)cancer. Analysis of 28 fresh frozen OSF samples and 6 site-matched controls, using a panel of 22 monoclonal antibodies, revealed changes in keratin 17 expression which correlated with disease severity. A mobile dental unit staffed by suitably experienced dentists and cultural advocates and equipped for immediate histological diagnosis of positive screened individuals is required in order to undertake effective and ethical oral cancer screening in high-risk UK based South Asian populations.

This thesis is an exploration of various aspects of oral health in the early-modern period. It examines evidence taken from texts belonging to a range of genres including surgical manuals, botanical texts, midwifery manuals, poets and plays. Building on existing academic work relating to the history of dentistry and venereal disease, it aims to assimilate material from across science and the arts in order to gain a sense of what general social expectations were in relation to the condition of the teeth and palate, and how people suffering with a decline in oral health were advised, or what treatments were available to them either from a professional or in the home. It aims to challenge existing preconceptions that people living in this period displayed a negligent attitude towards the health of their teeth and oral hygiene. The thesis contains four chapters which each focus on a different aspect of oral health, though many themes recur across all four chapters. The first chapter investigates advice that was available in print, and therefore likely to be in public consciousness, to the early-modern individual in relation to maintaining their teeth. It then considers the portrayal of unattractive teeth and bad breath in early-modern literature. Chapter Two deals with early-modern explanations of what caused the toothache and how it could be remedied. Analysis of the depictions of toothache in various poetry and plays follows in order to explore how wider society made sense of medical thinking at the time. The palate becomes the sole focus of Chapter Three, which considers what specific health concerns posed a threat to the condition of the roof of the mouth, and what difficulties could arise for the individual whose palate has been damaged by disease or injury. The thesis concludes with a chapter which investigates the history of a congenital oral birth defect, the cleft lip and palate. The thesis was designed to allow each chapter to deal with a separate facet of oral health; they encompass in turn: oral hygiene, dental pain, the impact of disease on the palate and an exploration of an oral birth defect. An undercurrent of the thesis is to use a range of material to ascertain a realistic idea of what it was like for an individual to experience oral health difficulties in this period. It is therefore interested in how society perceived people who were experiencing problems with their oral health, and what could be done to improve their quality of life. The research presented here represents a contribution to the field of the history of oral health and aims to provoke further questions relating to the responsibility early-modern individuals took for their own oral health, and the specific situations in which intervention, either surgical or medicinal, was deemed necessary.