PAR-2 Regulates Dental Pulp Inflammation Associated with Caries

Protease-activated receptors (PARs) are G-protein-coupled receptors that are activated enzymatically by proteolysis of an N-terminal domain. The cleavage and activation of PARs by serine proteases represent a novel mechanism by which such enzymes could influence the host inflammatory response. The aim of this study was to determine whether PAR-2 expression and activation were increased in dental caries. Using immunohistochemistry, we showed PAR-2 to be localized to pulp cells subjacent to caries lesions, but minimally expressed by healthy pulp tissue. Trypsin and the PAR-2 agonist (PAR2-AP) activated PAR-2 in an in vitro functional assay. Endogenous molecules present in pulp cell lysates from carious teeth specifically activated PAR-2, but those from healthy teeth failed to do so. The activation of PAR-2 in vitro was shown to increase the expression of the pro-inflammatory mediator cyclo-oxygenase-2 (COX-2), providing a mechanism whereby PAR-2 could modulate pulpal inflammation.

Caries incidence following tooth replacement for partially dentate elders

Objective: To compare caries incidence following two different tooth replacement strategies for partially dentate older patients; namely functionally orientated treatment according to the principles of the Shortened Dental Arch (SDA) and conventional treatment using Removable Partial Dentures (RPDs). Method:A randomised controlled clinical trial (RCT) was conducted of partially dentate patients aged 65 years and older. Patients were randomly allocated to two different treatment groups: the RPD group and the SDA group. Each member of the RPD group was restored to complete arches with cobalt-chromium RPDs used to replace missing teeth. Patients in the SDA group were restored to a shortened arch of 10 occluding pairs of natural and replacement teeth using adhesive bridgework. All of the operative treatment was completed by a single operator. Caries incidence was measured over a 2-year period following treatment intervention and recorded using the International Caries and Detection System (ICDAS). Result:In total, 89 patients completed the RCT (45 SDAs and 44 RPDs). Patients in the RPD group recorded a significantly higher incidence of new carious lesions (p<0.001) and recurrent carious lesions (p<0.001) compared to the SDA group. A mixed model of covariance (ANCOVA) revealed that treatment group (p<0.001) and co-morbidity (p<0.001) were significant predictors of caries incidence. Conclusion:Two years after provision of prosthodontic treatment there was a significantly higher incidence of new and recurrent caries lesions in subjects provided with RPDs compared with SDA treatment. This will have a significant impact on the ongoing maintenance costs for these two treatment groups.

Caries and the older patient

Ageing of the population, together with prolonged retention of teeth, has brought new challenges to dentistry. Whereas in the past oral care for the elderly was restricted to provision of dentures, older patients are now presenting with dental caries and failed restorations. These problems may have an impact on their general health and quality of life. Poor oral hygiene, xerostomia and diet are among the risk factors for caries in older patients and need to be addressed in order to achieve control of the disease. Carious lesions can be treated conservatively in many cases or may need surgical management.

CLINICAL RELEVANCE: Caries is an oral health issue among older patients and can result in tooth loss. Oral health has a great impact on general health and quality of life of elderly people.

Protease activated receptor 2 expression and functionality in caries

Introduction: Protease activated receptors (PARs) are G-protein-coupled transmembrane receptors that are expressed on many cell types and implicated in various inflammatory processes in vivo. The induction of PAR2 as a result of the inflammatory response associated with dental caries remains to be determined. Objectives: The aim was to localise the expression of PAR2 in human dental pulp from carious teeth and to confirm receptor functionality using an in vitro assay. Methods: Dental pulp sections from decalcified carious teeth were examined by immunocytochemsitry. Membrane preparations from cultured pulp fibroblasts were subject to SDS-PAGE and immunoblotting to confirm fibroblast-associated immunoreactivity. The functionality of PAR2 on dental pulp fibroblasts was studied using calcium imaging in the presence of several potential activators including a PAR2 agonist (PAR2-AP), trypsin and pulpal enzymes from a carious tooth. Results: Immunocytochemistry revealed intense PAR2 immunoreactivity on pulpal fibroblasts subjacent to carious lesions but not in surrounding regions of the dental pulp. Pulp specimens from a dental injury model showed no expression of PAR2, suggesting its expression was related to cellular changes associated with ongoing caries. The localisation of PAR2 staining to pulpal fibroblasts in carious teeth was confirmed by Western blotting which revealed PAR2 immunoreactive bands in membrane fractions prepared from pulp fibroblasts. In functional studies, challenge of cultured pupal fibroblasts with PAR2-AP, trypsin and an extract of proteolytic enzymes from a carious dental pulp, showed specific activation of PAR2. Conclusions: This work demonstrates that PAR2 is functional and inducible in human dental pulp fibroblasts in response to caries and that endogenous pulpal enzymes can activate PAR2.

The prevalence of caries in patients referred for orthodontic assessment in Northern Ireland – A retrospective study

Objectives: To determine the prevalence of untreated carious lesions in permanent teeth in patients (under the age of 18) referred for an orthodontic assessment in specialist practice. In addition, the figures shall be compared with national data for Northern Ireland (as outlined in the recent Child Dental Health Survey 2013)
The Gold standard would be that 100% of patients would be caries free upon presentation.

Methods: The clinical records and radiographs (OPT of quality grading 1 or 2) of 337 patients were reviewed. This encompassed patients who had an orthodontic assessment carried out in specialist practice over a 6 month period (following referral from their general dental practitioner)

Results: A total of 337 patient records were examined. Of these, 149 were male (44.2%) and 188 were female (55.8%), with an age range of 7-17 years at the time of new patient assessment. It was found that 36 patients (10.7%) had evidence (clinical and/or radiographic) of active and untreated dental caries. Of those affected, 14 were male and 22 were female.
Breaking the data down in terms of age, we can also get some indication as to how this cohort compares with national data for Northern Ireland :⃰

7-10 years (Mean = 9.3) = 14.3% caries (versus NI average of 6% for 8 year olds)
11-13 years (Mean = 12.1) = 10.1% caries, (versus NI average of 16% for 12 year olds)
14-17 years (Mean = 15.2) = 9.1% caries (versus NI average of 15% for 15 year olds)

⃰using the diagnostic threshold “Decay into dentine (visual dentine caries excluded)”


Conclusion: In this sample group, a total of 10.7% of patients (9.4% of males, 11.7% of females) presented with evidence of undiagnosed caries upon being assessed as a new patient in specialist orthodontic practice. Hence, the gold standard was not met.

Evaluation of a Water-soluble Bioadhesive Patch for Photodynamic Therapy of Vulval Lesions

An innovative bioadhesive patch intended primarily as a vulval drug delivery system and, specifically, as a means to deliver photosensitisers, or their prodrugs, for photodynamic purposes is described. The patch was formulated with a copolymer of methyl vinyl ether and maleic anhydride (PMVE/MA) as a bioadhesive matrix and poly(vinyl chloride) as a drug-impervious backing layer. Adhesive strength to neonate porcine skin, as a model substrate, was evaluated using peel and tensile testing measurements. Acceptabilities of non-drug loaded patches were appraised using human volunteers and visual-analogue scoring devices. An optimal formulation, with water uptake and peel strengths appropriate for vulval drug delivery, was cast from a 20% (w/w) PMVE/MA solution and adhered with a strength of approximately 1.7 N cm-2. Patient evaluation demonstrated comfort and firm attachment for up to 4 h in mobile patients. Aminolevulinic acid, a commonly used photosensitiser, was formulated into the candidate formulation and applied to vulval intraepithelial neoplastic lesions. Fluorescence under ultraviolet illumination revealed protoporphyrin synthesis. The patch achieves the extended application times obligatory in topical photodynamic therapy of vulval lesions, thereby contributing to potential methods for the eradication of neoplastic lesions in the lower female reproductive tract.

Anterior thalmic lesions stop immediate early gene activation in selective laminae of the retrosplenial cortex: evidence of covert pathology in rats

Lesions involving the anterior thalamic nuclei stopped immediate early gene (IEG) activity in specific regions of the rat retrosplenial cortex, even though there were no apparent cytoarchitectonic changes. Discrete anterior thalamic lesions were made either by excitotoxin (Experiment 1) or radiofrequency (Experiment 2) and, following recovery, the rats foraged in a radial-arm maze in a novel room. Measurements made 6-12 weeks postsurgery showed that, in comparison with surgical controls, the thalamic lesions produced the same, selective patterns of Fos changes irrespective of method. Granular (caudal granular cortex and rostral granular cortex), but not dysgranular (dysgranular cortex), retrosplenial cortex showed a striking loss of Fos-positive cells. While a loss of between 79 and 89% of Fos-positive cells was found in the superficial laminae, the deeper layers appeared normal. In Experiments 3 and 4, rats 9-10 months postsurgery were placed in an activity box for 30 min. Anterior thalamic lesions (Experiment 3) led to a pronounced IEG decrease of both Fos and zif268 throughout the retrosplenial cortex that now included the dysgranular area. These IEG losses were found even though the same regions appeared normal using standard histological techniques. Lesions of the postrhinal cortex (Experiment 4) did not bring about a loss of retrosplenial IEG activity even though this region is also reciprocally connected with the retrosplenial cortex. This selective effect of anterior thalamic damage upon retrosplenial activity may both amplify the disruptive effects of anterior thalamic lesions and help to explain the posterior cingulate hypoactivity found in Alzheimer's disease.

Changes in fos expression in the rat brain after unilateral lesions of the anterior thalamic nuclei

Activity of the immediate early gene c-fos was compared across hemispheres in rats with unilateral anterior thalamic lesions. Fos protein was quantified after rats performed a spatial working memory test in the radial-arm maze, a task that is sensitive to bilateral lesions of the anterior thalamic nuclei. Unilateral anterior thalamic lesions produced evidence of a widespread hippocampal hypoactivity, as there were significant reductions in Fos counts in a range of regions within the ipsilateral hippocampal formation (rostral CA1, rostral dentate gyrus, 'dorsal' hippocampus, presubiculum and postsubiculum). A decrease in Fos levels was also found in the rostral and caudal retrosplenial cortex but not in the parahippocampal cortices or anterior cingulate cortices. The Fos changes seem most closely linked to sites that are also required for successful task performance, supporting the notion that the anterior thalamus, retrosplenial cortex and hippocampus form key components of an interdependent neuronal network involved in spatial mnemonic processing.