A connectivity mapping approach predicted acetylsalicylic acid (aspirin) to induce osteo/odontogenic differentiation of dental pulp cells.

AIM: To use connectivity mapping, a bioinformatics approach, to identify compounds that could induce odontogenic differentiation of dental pulp cells (DPCs) and to experimentally validate this effect. A subsidiary aim was to investigate the anti-inflammatory effect of any identified compound. METHODOLOGY: The Gene Expression Omnibus (GEO) database was searched for microarray data sets assessing odontogenic differentiation of human DPCs. An odontogenic gene expression signature was generated by differential expression analysis. The statistical significant connectivity map (ssCMap) method was used to identify compounds with a highly correlating gene expression pattern. DPCs were treated with the compound identified, and osteo/odontogenic differentiation was assessed by Alizarin red staining, alkaline phosphatase activity and expression of osteo/odontogenic genes ALPL, RUNX2, COL1A1, DSPP, DMP1 and SPP1 by RT-PCR. The anti-inflammatory effect of the compound was assessed using an ex vivo pulpitis model, and cytokine levels were measured with multiplex assay. Means were compared using the t-test or ANOVA followed by a Bonferroni post hoc test with the level of significance set at P ≤ 0.05. RESULTS: The GEO database search identified a specific gene expression signature for osteo/odontogenic differentiation. Analysis using ssCMap found that acetylsalicylic acid [(ASA)/aspirin] was the drug with the strongest correlation with that gene signature. The treatment of DPCs with 0.05 mmol L-1 ASA showed increased alkaline phosphatase activity (P < 0.001), mineralization (P < 0.05), and increased the expression of the osteo/odontogenic genes, DMP1 and DSPP (P < 0.05). Low concentration (0.05 mmol L-1 ) ASA reduced inflammatory cytokines IL-6 (P < 0.001), CCL21 (P < 0.05) and MMP-9 (P < 0.05) in an ex vivo pulpitis model. CONCLUSIONS: Connectivity mapping, a web-based informatics method, was successfully used to identify aspirin as a candidate drug that could modulate the differentiation of DPCs. Aspirin was shown to induce odontogenic differentiation in DPCs in vitro and this, together with its anti-inflammatory effects, makes it a potential candidate for vital pulp therapies.

Matrix metalloproteinase-8 activity in gingival crevicular fluid: development of a novel assay.

BACKGROUND AND OBJECTIVE: The matrix metalloproteinases (MMPs) play a role in regulating turnover and metabolism of connective tissues in health but they have also been implicated in a wide variety of pathological conditions, including periodontal disease. MMP-8 has been extensively studied in periodontal health and disease using ELISA, although this technique is limited by its inability to determine enzyme activity. The aim was to develop an assay specifically to measure MMP-8 activity and to demonstrate its use in the analysis of gingival crevicular fluid samples. MATERIAL AND METHODS: A specific antibody was used to coat black 96-well microtitre plates to capture MMP-8 selectively. The activity of bound MMP-8 was measured using a fluorogenic substrate. Gingival crevicular fluid samples, from healthy and periodontally diseased sites, were collected using PerioPaper strips and tested for MMP-8 activity. RESULTS: Significantly higher MMP-8 activity was demonstrated in gingival crevicular fluid from periodontally diseased sites compared with healthy sites that exhibited basal or no MMP-8 activity. No cross-reactivity with other MMPs was noted. CONCLUSION: We show, for the first time, that MMP-8 activity can be specifically detected and quantified in gingival crevicular fluid samples. Measurement of MMP-8 activity could prove to be useful in monitoring periodontal disease progression.

Neuropeptide Y Y1 receptor in human dental pulp cells of noncarious and carious teeth.

AIM: To determine the distribution of the NPY Y1 receptor in carious and noncarious human dental pulp tissue using immunohistochemistry. A subsidiary aim was to confirm the presence of the NPY Y1 protein product in membrane fractions of dental pulp tissue from carious and noncarious teeth using western blotting. METHODOLOGY: Twenty two dental pulp samples were collected from carious and noncarious extracted teeth. Ten samples were processed for immunohistochemistry using a specific antibody to the NPY Y1 receptor. Twelve samples were used to obtain membrane extracts which were electrophoresed, blotted onto nitrocellulose and probed with NPY Y1 receptor antibody. Kruskal-Wallis one-way analysis of variance was employed to test for overall statistical differences between NPY Y1 levels in noncarious, moderately carious and grossly carious teeth. RESULTS: Neuropeptide Y Y1 receptor immunoreactivity was detected on the walls of blood vessels in pulp tissue from noncarious teeth. In carious teeth NPY Y1 immunoreactivity was observed on nerve fibres, blood vessels and inflammatory cells. Western blotting indicated the presence and confirmed the variability of NPY Y1 receptor protein expression in solubilised membrane preparations of human dental pulp tissue from carious and noncarious teeth. CONCLUSIONS: Neuropeptide Y Y1 is expressed in human dental pulp tissue with evidence of increased expression in carious compared with noncarious teeth, suggesting a role for NPY Y1 in modulation of caries induced pulpal inflammation.

Putative periodontal pathogens in the subgingival plaque of Sudanese subjects with aggressive periodontitis.

BACKGROUND AND OBJECTIVES: There has been limited study of the bacterial species associated with aggressive periodontitis (AgP) in high-risk populations in Africa. The aim of this study was to investigate and quantify the presence of four putative periodontal pathogens in the subgingival plaque of Sudanese subjects with AgP. A secondary aim was to investigate the effect of varying the detection threshold on the reported prevalence of the bacterial species investigated. MATERIALS AND METHODS: Subgingival plaque samples were collected from AgP cases (n=73) and healthy controls (n=71). Bacterial DNA was extracted and analyzed by quantitative polymerase chain reaction for the detection and quantification of four putative periodontal pathogens: Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Treponema denticola and Tannerella forsythia. RESULTS: At the lowest detection threshold (>101 cells), P. gingivalis (p<0.0001) was more prevalent in AgP cases than controls. T. forsythia and T. denticola had a high prevalence (>70%) in AgP cases at all detection levels. While T. forsythia was significantly more frequently identified in AgP than in controls at all detection thresholds, this was only the case for T. denticola at the intermediate threshold (>102 cells). A. actinomycetemcomitans was identified less frequently than the other bacterial species with no difference in its prevalence between AgP cases and controls. CONCLUSION: The prevalence of the putative periodontal pathogens investigated varied considerably in Sudanese subjects with AgP and in periodontally healthy controls depending on the detection thresholds applied. T. forsythia was identified as having the strongest association with AgP.

Detection of individual human neutrophil alpha-defensins (human neutrophil peptides 1, 2 and 3) in unfractionated gingival crevicular fluid--a MALDI-MS approach.

The role of antimicrobial peptides is particularly important in the oral cavity where there is constant challenge by microorganisms. The alpha-defensins are a group of cationic peptides that comprise 30-50% of the total protein in azurophilic granules of human neutrophils. They include the human neutrophil peptides (HNP) 1, 2 and 3 which have almost identical amino acid sequences but differ in their biological activities. The amino acid sequence similarities of the defensins have made it difficult to unequivocally determine the presence of individual defensins using antibody-based techniques. However, by virtue of their cationic nature we postulated that the defensins would fly particularly well in mass spectrometry and that this characteristic would allow facile identification of individual HNPs in unfractionated gingival crevicular fluid (GCF) from periodontitis patients and healthy controls. Although there was variability in levels of defensins detected in periodontal health and disease, HNP-1 was always identified as the major peak in the triad and HNP-3 as the minor peak, lending support to the hypothesis that HNP-2 may arise by post-translational proteoyltic cleavage of HNP-3 rather than HNP-1. The finding that the defensins were more abundant in a higher proportion of the healthy sites studied could be linked to a more intact defensin barrier in periodontal health.

The efficacy of the selective serotonin reuptake inhibitors for social anxiety disorder (social phobia): a meta-analysis of randomized controlled trials.

This article reviews all available studies on the use of selective serotonin reuptake inhibitors (SSRIs) for the pharmacotherapy of social anxiety disorder. Using the search methods laid out by the Cochrane Collaboration, 25 published reports of SSRI effectiveness for social anxiety disorder were identified, of which eight were randomized, double-blind, placebo-controlled trials (RCTs). The odds ratios of responder status ('much improved' or 'very much improved' on the Clinical Global Impression Scale) for SSRI versus placebo varied between 2.1 and 26.2. In no RCT was the lower confidence limit less than 1. The number needed to treat varied from 1.6 to 4.2. The number of patients who responded to drug was approximately twice the number who responded to placebo. Comparing the change in mean Liebowitz Social Anxiety Scale score in patients treated with drug versus those treated with placebo, the effect sizes of the RCTs varied from 0.3 to 2.2. In four RCTs the effect size was 'large', in one 'moderate' and in two 'small'. Furthermore, response rates and effect sizes for SSRIs were larger than those seen in trials of the reversible monoamine oxidase inhibitors (RIMAs). It may be concluded with a high degree of confidence that SSRI treatment for social anxiety disorder is effective, both in reducing total levels of social anxiety and in improving patients' overall clinical condition.

Selective serotonin reuptake inhibitors in the treatment of post-traumatic stress disorder: a meta-analysis of randomized controlled trials.

Advances in the neurobiology of post-traumatic stress disorder (PTSD) and the availability of modern psychotropics have led to renewed interest in the pharmacotherapy of this disorder. In this paper we focus on trials of the selective serotonin reuptake inhibitors (SSRIs) in PTSD. Studies of the pharmacotherapy of PTSD were identified using methods developed by the Cochrane collaboration. Although a range of open trials of different SSRIs in PTSD show promise, there are few controlled pharmacotherapy studies in this disorder. Nevertheless, pharmacotherapy for PTSD appears to have reasonably robust effects, with odds ratios for responder status, defined as 'much improved' or 'very much improved' on the Clinical Global Impression Scale (CGI), on drug versus placebo varying from 2.2 to 5.6 in randomized controlled trials of different agents. The SSRIs appear both safe and effective for this indication. Additional research with these agents is necessary to clarify many questions, including predictors of response, duration of treatment, comparison with other agents, and integration with psychotherapy. In the interim, however, the SSRIs can be recommended as a first-line medication for the treatment of PTSD.

Cigarette smoking and periodontal destruction in young adults.

The relationship between cigarette smoking and periodontal destruction was assessed in young adults. Eighty-two regular dental attenders (21 current cigarette smokers, 61 non-smokers) aged between 20 and 33 years were examined. The smokers consumed on average 15.4 (+/- 7.3) cigarettes per day and had smoked for an average of 11.8 (+/- 7) years. Cigarette smokers had almost the same levels of plaque as non-smokers but had more proximal surfaces with subgingival calculus (P < 0.01) and which bled on probing (P < 0.05). Smokers had significantly more pockets > or = 4 mm (14.6 +/- 19.9) than non-smokers (5.8 +/- 7.9), P < 0.01. Only 2 (10%) of the smokers and 1 (2%) of the non-smokers had deep pocketing (> or = 6 mm). Smokers had significantly more sites (21.8 +/- 24.9) with periodontal attachment loss of > or = 2 mm than non-smokers (9.3 +/- 12.2), P < 0.01. Severe loss of periodontal attachment (> or = 6 mm) was present in 4 (19%) of smokers compared with 2 (3%) of non smokers. In total 4 (19%) of the smokers had "established periodontitis" compared with 1 (2%) of the non-smokers. The odds ratio for the presence of "established periodontitis" and smoking was 14.1 (confidence interval 1.5 to 132.9). It is concluded that cigarette smoking was a major environmental factor associated with accelerated periodontal destruction in this selected group of young adult regular dental attenders.

Smoking and patterns of bone loss in early-onset periodontitis.

BACKGROUND: The aims of this study were to investigate the extent and distribution of bone loss in subjects with early-onset periodontitis (EOP) referred for periodontal care and to study the relationship between smoking and EOP. METHODS: A total of 71 consecutive referrals (21 male, 50 female) under 35 years old, who were otherwise healthy, with a clinical diagnosis of severe periodontitis were recruited for the study. Bone loss was measured from available radiographs using a Schei ruler to identify 2 patterns of destruction: localized (LEOP) in 41 (58%) and generalized early-onset periodontitis (GEOP) in 30 (42%) subjects. RESULTS: The study population had a mean of 25.0 (SD 2.4) teeth, excluding third molars, and mean bone loss of 28.7% (SD 13.0). Bone loss was more severe in the maxilla, 30.9% (SD 13.8) compared with 26.6% (SD 14.0) in the lower arch. More than one-third (36%) of the teeth examined had at least 30% bone loss. Mean smoking experience was 9.2 pack years (SD 5.6), and 39 (55%) of the EOP subjects smoked. Smokers had significantly more maxillary bone loss than non-smokers. A much higher proportion of GEOP (70%) currently smoked compared with 44% of LEOP, P = 0.029. CONCLUSIONS: It is concluded that young adults with early-onset forms of periodontitis often have advanced periodontal destruction before they are referred for specialist care. In addition, there was a relationship between smoking and severe bone destruction in subjects with EOP, particularly those with generalized disease.

The effects of culture environment on the response of human gingival fibroblasts to cyclosporin A.

In contrast to monolayer cell culture, the use of a 3-dimensional culture system creates an environment which is more physiologically comparable to conditions in vivo. This study aimed to investigate the effects of culture environment on growth and protein biosynthesis by 6 human gingival fibroblast cell lines exposed to cyclosporin A (CsA). Fibroblasts were grown both in monolayer culture on plastic and embedded within collagen gel. Cyclosporin A was added to cultures at a range of concentrations between 10(-5) and 10(-9) g/ml. Under both culture conditions CsA had little effect on cell growth at low concentrations but at the highest concentration of 10(-5) g/ml, there was a significant inhibitory effect on growth (P < 0.05). Protein production was not significantly affected by CsA in either culture system. Total collagen production appeared to be inhibited at high concentrations of CsA when cells were grown on plastic but remained unaffected when the cells were grown in collagen gel. Total protein and collagen production per cell in collagen gel was substantially greater compared with cells grown on plastic. We conclude that under the conditions of this investigation CsA did not directly stimulate growth or matrix-synthesis by normal human gingival fibroblasts cultured in 3-dimensional collagen gel or as monolayers on plastic.

Cyclosporin A regulates interleukin-1beta and interleukin-6 expression in gingiva: implications for gingival overgrowth.

BACKGROUND: Gingival overgrowth is a common side effect following the administration of cyclosporin A (CsA); however, the cellular mechanisms remain poorly understood. CsA's immunosuppressant properties involve the regulation of synthesis and cellular response to cytokines. A CsA-induced alteration in the cytokine profile within gingival tissue could provide a mechanism for gingival hyperplasia. The aim of this study was to investigate the effects of CsA on the production of 2 cytokines - interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) - by both gingival fibroblasts and peripheral blood mononuclear cells (PBMC). METHODS: Cells were stimulated for 24 hours in the presence of CsA over a concentration range of 100 to 2,000 ng/ml and the resultant cytokine production determined by ELISA. In addition, levels of both cytokines within normal, inflamed, and overgrown gingival tissue were determined. RESULTS: CsA inhibited IL-6 production by gingival fibroblasts in a dose-dependent manner. In contrast, at a concentration of 2,000 ng/ml, CsA stimulated IL-6 production by PBMC (P <0.05). Fibroblasts derived from overgrown gingiva produced significantly higher levels of IL-6 than their normal counterparts (P <0.05). CsA inhibited IL-1beta production by PBMC over the whole concentration range (P <0.05). IL-1beta was not found in measurable quantities in any of the fibroblast cultures. Levels of IL-6 extracted from overgrown gingival tissue were significantly higher than in inflamed or normal tissue. In contrast IL-1beta levels in overgrown tissue were not statistically significantly greater than those in inflamed tissue. CONCLUSIONS: These results show that CsA does regulate cytokine expression in gingival tissue. This effect may play an important role in the pathogenesis of CsA-induced gingival overgrowth.

The influence of transforming growth factor-beta1 gene polymorphisms on the severity of gingival overgrowth associated with concomitant use of cyclosporin A and a calcium channel blocker.

BACKGROUND: The purpose of this study was to determine whether the prevalence and severity of gingival overgrowth in renal transplant recipients concomitantly treated with cyclosporin and a calcium channel blocker was associated with functional polymorphisms within the signal sequence of the transforming growth factor-(TGF)beta1 gene. METHODS: The extent and severity of gingival overgrowth for 164 renal transplant recipients immunosuppressed with cyclosporin A and concomitantly taking a calcium channel blocker since transplant were entered into the study (86 in Manchester, 78 in Belfast). Two biallelic polymorphisms of the TGF-beta1 gene were studied at position +869, codon 10 (leucine to proline substitution), and position +915, codon 25 (arginine to proline substitution). RESULTS: Subjects who were homozygous for proline at codon 10 had significantly higher overgrowth scores than those who were heterozygous (P= 0.03) or homozygous for leucine (P= 0.01). Subjects who were heterozygous (arginine/proline) at codon 25 had a significantly higher (P= 0.04) gingival overgrowth score than those who were homozygous for arginine. Logistic regression analysis indicated that for codon 25 independent predictors of severe gingival overgrowth were the heterozygous arginine/proline genotype (P= 0.009) and whether the individual was young (P= 0.05). CONCLUSIONS: Polymorphisms in the TGF-beta1 gene influence the expression of gingival overgrowth in renal transplant recipients concomitantly treated with cyclosporin and a calcium channel blocker. The polymorphism in the TGF-beta1 gene at codon 25 represented an independent genetic determinant of severe gingival overgrowth in the susceptible subjects studied.

Extraction and radioimmunoassay quantitation of neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP) from human dental pulp tissue.

The measurement of neuropeptides in complex biological tissue samples requires efficient and appropriate extraction methods so that immunoreactivity is retained for subsequent radioimmunoassay detection. Since neuropeptides differ in their molecular mass, charge and hydrophobicity, no single method will suffice for the optimal extraction of various neuropeptides. In this study, dental pulp tissue was obtained from 30 human non-carious teeth. Of the three different neuropeptide extraction methods employed, boiling in acetic acid in the presence of protease inhibitors yielded the highest levels of neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP). High pressure liquid chromatography (HPLC) analysis of dental pulp tissue verified the authenticity of the neuropeptides extracted.

A comparison of four extraction methods for substance P, neurokinin A and calcitonin gene-related peptide from human dental pulp tissue.

Measuring neuropeptides in biological tissues by radioimmunoassay requires efficient extraction that maintains their immunoreactivity. Many different methods for extraction have been described, but there is little information on optimal extraction methods for individual neuropeptides from human dental pulp tissue. The aim was therefore to identify an effective extraction procedure for three pulpal neuropeptides; substance P, neurokinin A and calcitonin gene-related peptide. Tissue was obtained from 20 pulps taken from teeth freshly extracted for orthodontic reasons. The pulp samples were divided into four equal groups and different extraction methods were used for each group. Boiling whole pulp in acetic acid gave the highest overall yield and, in addition, offered an easy and rapid means of pulp tissue processing. The use of protease inhibitors did not increase the recovery of the immunoreactive neuropeptides but did provide the best combination of maximal recoveries and minimal variability. These results should be useful for planning the extraction of these neuropeptides from human pulp tissue in future studies.

Knowledge, attitudes and behaviour in relation to dental health of adults in Belfast, Northern Ireland.

The aim was to investigate the knowledge, attitudes and behaviour related to dental health of adults living in two neighbouring areas in Belfast, Northern Ireland. 81 adults aged 30 yr or over from two neighbouring residential areas in South Belfast completed a structured interview. The responses of those who retained natural teeth were very different from those who were edentulous. Those in the higher socioeconomic status groups had clearer knowledge, more positive attitudes and more appropriate behaviour related to dental health than those in lower socioeconomic status groups. The differences between the residents of the two areas were less obvious than those noted between the different socioeconomic status groups. It was concluded that the results revealed misconceptions amongst adults in Northern Ireland regarding the causes of dental disease and how it might be prevented both in themselves and in their children.

Overhanging amalgam restorations in young adults attending a periodontal department.

An important factor affecting plaque retention is the presence of amalgam restorations which are poorly contoured at the gingival margin. The aim of the study was to investigate the occurrence and effects of overhanging amalgam restorations in young adults. One hundred patients, aged 20-29 years, referred to the Periodontal Department, School of Dentistry, Belfast were investigated. Bitewing radiographs were used to examine the restorative status of the approximal surfaces of premolar and permanent molar teeth, excluding third molars. Fifty-seven per cent of the patients investigated had at least one amalgam overhang and 27 per cent had three or more overhangs visible on the radiographs. One hundred and seventy-eight (25 per cent) of the restored approximal surfaces had detectable amalgam overhangs. The mean bone level-amelocemental junction (ACJ) distance related to the approximal surfaces with overhangs was 1.77 (s.d. 1.0) mm and 37 (32 per cent) of these surfaces had bone levels which were greater than 2 mm from the ACJ. The mean bone level-ACJ distance for the other approximal surfaces of the teeth with overhangs was 1.63 (s.d. 1.2) mm. The mean bone level-ACJ distance for matching control surfaces on contralateral teeth was 1.86 (s.d. 1.2) mm. It was concluded that overhanging amalgam restorations were common in the restorations of young adults (20-29 years old) referred for periodontal treatment but were not associated with increased levels of bone destruction.

The clinical performance of cantilevered resin-bonded bridgework.

OBJECTIVES: The technique of resin-bonded bridgework is a well-accepted clinical technique to replace missing teeth. This study assesses the clinical performance of cantilevered resin-bonded bridgework provided in a university teaching hospital environment. METHODS: One-hundred and twelve patients who had a total of 142 cantilevered bridges were either examined or completed a questionnaire regarding their bridgework. The following data were recorded for each resin-bonded bridge: gender of patient, age at bridge cementation, date of initial cementation, tooth replaced, abutment(s) involved, and grade of clinician responsible for the provision of the bridge. Details of the incidence of debonding with date(s) and the subsequent treatment in relation to the debonded resin-bonded bridge were recorded. The subjects examined indicated their degree of satisfaction with their bridgework on a visual analogue scale. RESULTS: There were 112 patients with a total of 142 bridges, 116 (82%) maxillary and 26 (18%) mandibular. The mean length of clinical service was 36.2 months (s.d. 17.2 months). Only single pontics were included in the bridges, with almost half (49%) replacing a lateral incisor. Of the cantilever resin-bonded bridges studied, 88% remained bonded over the period of the study. A success rate of 94% is reported. CONCLUSION: This study confirms the clinical success of cantilever resin-bonded bridges particularly in the replacement of maxillary lateral incisors, maxillary premolar and permanent mandibular teeth.

Performance of 400 adhesive bridges fitted in a restorative dentistry department.

The purpose was to present a descriptive report of the clinical performance of adhesive bridges fitted in a university department of restorative dentistry. The case records of 400 consecutive adhesive bridges fitted between November 1984 and June 1989 in the School of Clinical Dentistry, Queen's University, Belfast were reviewed. The majority of the bridges (66 per cent) were of a fixed-fixed Maryland design; the remainder were Maryland cantilevers (18 per cent), hybrids, i.e. Maryland cantilevers which slotted into conventional units (8 per cent), and Rochette bridges (6 per cent). The mean duration of clinical service at review was 2.7 years. One hundred (25 per cent) of the bridges debonded on at least one occasion. Of the bridges which debonded the average number of debonds was 1.7, with the first debond happening on average 10.7 months after placement (range 1-42 months). Fifty-seven (14 per cent) debonded on one occasion only; 25 (6 per cent) debonded twice and 18 (5 per cent) debonded on three or four occasions. The length of clinical service was a significant factor in relation to debonding. A lower proportion of posterior than anterior bridges debonded and cantilevered and hybrid designs performed well. It is concluded that this investigation confirms the efficacy of resin-bonded bridgework used to replace both anterior and posterior teeth.

Dental anxiety and the absorption of orally administered erythromycin stearate.

Erythromycin stearate is an acid labile antibiotic, therefore fear and apprehension, which are known to affect gastric motility, may produce erratic absorption resulting in lower serum levels. The mean (SD) serum erythromycin concentration 75 minutes after a 1.5 gm oral dose of erythromycin stearate to 45 patients was 8.7 (4.8) mg/L and ranged widely from 0.4 to 20.5 mg/L. The serum concentration of erythromycin was below therapeutic levels (1.0 mg/L) in two patients. No significant association was found between anxiety and serum levels of erythromycin when age, gender, and gastric distress were taken into account. It is concluded that dental anxiety may indirectly influence the uptake of oral erythromycin stearate; but this relationship is complex, and there is no evidence from this study that increased dental anxiety decreases the uptake of the drug.

Occlusal considerations in periodontics.

Periodontal disease does not directly affect the occluding surfaces of teeth, consequently some may find a section on periodontics a surprising inclusion. Trauma from the occlusion, however, has been linked with periodontal disease for many years. Karolyi published his pioneering paper, in 1901 'Beobachtungen uber Pyorrhoea alveolaris' (occlusal stress and 'alveolar pyorrhoea'). (1) However, despite extensive research over many decades, the role of occlusion in the aetiology and pathogenesis of inflammatory periodontitis is still not completely understood.