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.

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.

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.

Periodontitis, cardiovascular disease and pregnancy outcome--focal infection revisited?

Over the last two decades there has been a renewed interest around the possible effects of periodontal disease on both cardiovascular health and pregnancy outcome (among other diseases), a topic which has interested science for hundreds of years. These have led to a range of studies, workshops and consensus documents being published, with corresponding coverage in general and professional media. In this article the authors summarise the history and supporting theories behind such associations, whether clinical studies have been able to confirm these and what this might mean for general practitioners who are questioned on this topic by patients.

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.

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.

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.

NEUROPEPTIDES AND NEUROGENIC MECHANISMS IN ORAL AND PERIODONTAL INFLAMMATION.

It is generally accepted that the nervous system contributes to the pathophysiology of peripheral inflammation, and a neurogenic component has been implicated in many inflammatory diseases, including periodontitis. Neurogenic inflammation should be regarded as a protective mechanism, which forms the first line of defense and protects tissue integrity. However, severe or prolonged noxious stimulation may result in the inflammatory response mediating injury rather than facilitating repair. This review focuses on the accumulating evidence suggesting that neuropeptides have a pivotal role in the complex cascade of chemical activity associated with periodontal inflammation. An overview of neuropeptide synthesis and release introduces the role of neuropeptides and their interactions with other inflammatory factors, which ultimately lead to neurogenic inflammation. The biological effects of the neuropeptides substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), and neuropeptide Y (NPY) are summarized, and evidence for their involvement in the localized inflammatory lesions which characterize periodontitis is presented. In this context, the role of CGRP in bone metabolism is described in more detail. Recent research highlighting the role of the nervous system in suppressing pain and inflammation is also discussed.

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.

Quantitative analysis of substance P, neurokinin A and calcitonin gene-related peptide in pulp tissue from painful and healthy human teeth.

AIM: The purpose of this study was to investigate the levels of substance P (SP), neurokinin A (NKA) and calcitonin gene-related peptide (CGRP) in painful and healthy human dental pulps. METHODOLOGY: Forty-six samples of pulp tissue were collected from extracted or endodontically treated painful teeth and 20 from clinically healthy teeth extracted for orthodontic reasons. All pulp samples were boiled in 0.5 m acetic acid for 10 min, centrifuged and the supernatant collected. SP, NKA and CGRP levels were measured using radioimmunoassay. RESULTS: Substance P and CGRP were present in all samples and NKA was detected in 96% of the pulps. CGRP was present in much higher concentrations than SP and NKA in both painful and non-painful teeth. The painful teeth had significantly higher concentrations of SP (P = 0.02), NKA (P < 0.001) and CGRP (P = 0.03) than non-painful teeth. The concentration of CGRP was significantly higher in the pulps of smokers compared with non-smokers (P = 0.02). CONCLUSIONS: Elevated levels of these neuropeptides in pulps from painful teeth indicate that they may play an important role in the process of pulpal inflammation and pain. Further investigation of the association between these neuropeptides and pulpal status may help to improve our understanding of pulpal inflammation and dental pain.

Quantitative analysis of MRP-8 in gingival crevicular fluid in periodontal health and disease using microbore HPLC.

BACKGROUND: The protein components of GCF can be separated by reverse-phase microbore HPLC on a C18 column with detection on the basis of 214 nm absorbance. A single major symmetrical protein peak eluting with a retention time of 26 min (50% acetonitrile) was evident in gingival crevicular fluid (GCF) from periodontitis patients but not in healthy GCF. This protein was identified as human MRP-8 by N-terminal amino acid sequencing and liquid chromatography quadropole mass spectrometry. AIMS: To quantify the amount of MRP-8 detectable in GCF from individual healthy, gingivitis and periodontitis affected sites and to study the relationship, if any, between the levels of this responsive protein and periodontal health and disease. METHODS: GCF was sampled (30 s) from healthy, gingivitis, and periodontitis sites in peridontitis subjects (n=15) and from controls (n=5) with clinically healthy gingiva and no periodontitis. Purified MRP-8 was sequenced by Edmann degradation and the phenylthiohydantoin (PTH) amino acid yield determined (by comparison of peak area with external PTH amino acid standards). This value was subsequently used to calculate the relative amount of protein in the peak eluting with a retention time of 26.0 min (MRP-8) in individual GCF chromatograms. RESULTS: Higher levels of MRP-8 were detected in inflammatory sites: periodontitis 457.0 (281.0) ng; gingivitis 413.5 (394.5) ng compared with periodontally healthy sites in diseased subjects 14.6 (14.3) ng and in controls 18.6 (18.5) ng, p=0.003. There was at least 20-fold more MRP-8 in the inflammatory compared with the healthy sites studied. CONCLUSIONS: The preliminary data indicate that MRP-8 is present in GCF, with significantly greater amounts present at diseased than healthy sites. A systematic study of the relationship of this protein to periodontal disease could prove useful in further clarifying whether MRP-8 could be a reliable GCF biomarker of gingivitis and periodontitis.

Pre-treatment conceptions of periodontal disease and treatment in periodontal referrals.

BACKGROUND: Patients preconceptions of periodontal therapy have not been extensively studied and are poorly understood. AIMS: To register specific anxieties and preconceptions held by patients referred for specialist periodontal treatment and to investigate the risks such patients were prepared to take of progressive periodontal problems before deciding that periodontal treatment was necessary. MATERIALS AND METHODS: 79 patients referred for specialist treatment completed a structured questionnaire. Participants completed visual analogue scales to quantify the risks which they were prepared to take of various symptoms of periodontal disease before they believed treatment was essential. RESULTS: The majority (71%) had anxieties about pending treatment with the main concern being pain. Those who had sought information prior to treatment mainly did so from close relatives. The majority of patients opted to take no or a very low (<20%) risk of any periodontal problems and, therefore, were supportive of treatment. The loss of many teeth due to periodontal disease was the least acceptable outcome followed by tooth mobility. Patients were prepared to accept a significantly higher risk of bleeding on brushing (p<0.0001) than any of the other outcomes investigated. Females recorded substantially lower risk scores than males particularly in relation to developing recession or tooth mobility in the absence of treatment. Patients who were worried about experiencing pain during treatment recorded lower risk scores than those who had no anxiety regarding pain. CONCLUSION: It is concluded that the Norwegian periodontal referrals studied were prepared to take very low risks of further periodontal symptoms despite high levels of anxiety and evidence of a lack of knowledge regarding periodontal treatment.

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.

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.

Identification of MRP-8 (calgranulin A) as a major responsive protein in chronic periodontitis.

The purpose of the study was to analyse how the protein composition of the inflammatory exudate associated with chronic periodontitis differed from the exudate in periodontal health. Gingival crevicular fluid (GCF) was collected from sites with chronic periodontal inflammation and from non-diseased sites in healthy control subjects. Microbore HPLC analysis revealed one major difference in GCF protein profiles between healthy controls and periodontitis patients. The protein enhanced in periodontitis patients was identified as migration inhibitory factor-related protein-8 (MRP-8) by a combination of N-terminal amino acid sequencing, mass spectrometry, and SDS-PAGE. Together, these data demonstrate, for the first time, the presence of monomeric MRP-8 in an inflammatory exudate. Whether monomeric MRP-8 is a unique feature of chronic periodontal inflammation is not yet clear, but the chemotactic properties of this peptide support a functional role for MRP-8 in periodontal inflammation.

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.

Carboxypeptidase-mediated metabolism of calcitonin gene-related peptide in human gingival crevicular fluid--a rôle in periodontal inflammation?

BACKGROUND: Metabolism by peptidases plays an important rôle in modulating the levels of biologically-active neuropeptides. The metabolism of the anti-inflammatory neuropeptide calcitonin gene-related peptide (GCRP), but not the pro-inflammatory neuropeptides substance P (SP) and neurokinin A (NKA) by components of the gingival crevicular fluid (GCF), could potentiate the inflammatory process in periodontitis. AIMS: To characterise the extracellular hydrolysis of CGRP as a mechanism for the selective inactivation of this neuropeptide in GCF from periodontitis sites. METHODS: Samples of GCF from periodontitis patients and periodontally-healthy subjects were incubated with synthetic human SP, NKA or CGRP. Reaction between the GCF constituents and synthetic peptides was allowed to progress from 0-180 min. Results of neuropeptide metabolism at each time were analysed by matrix-assisted laser desorption/ionisation mass spectrometry. RESULTS: There was no evidence of metabolism of SP, NKA or CGRP by constituents of healthy GCF. Metabolism of synthetic SP and NKA was minimal even after extensive incubation with periodontitis GCF. However, loss of carboxy-terminal amino acids was evident after only 1 min incubation with periodontitis GCF. The pattern of CGRP metabolism, which proceeded from the C-terminus, indicated that the neuropeptide was degraded by a carboxypeptidase. After 180 min, there was extensive carboxypeptidase degradation of CGRP to an 11 amino acid peptide. CONCLUSIONS: It is concluded that carboxypeptidase activity in GCF from periodontitis patients is responsible for rapid breakdown of CGRP but not SP or NKA. The rapid action of this carboxypeptidase on the anti-inflammatory neuropeptide CGRP is suggestive of a pathophysiological rôle for the enzyme in selectively degrading CGRP, thereby potentiating periodontal inflammation.

Changes in substance P and neurokinin A in gingival crevicular fluid in response to periodontal treatment.

BACKGROUND: The study of periodontitis provides a unique model for assessing the involvement of neuropeptides in inflammatory disease. AIM: To investigate the effects of periodontal treatment, resulting in a return to periodontal health, on the levels of substance P (SP) and neurokinin A (NKA) in gingival crevicular fluid (GCF). METHOD: We completed a cause of non-surgical treatment for 8 subjects with periodontitis (6 females 2 males, mean age 45.1, range 38-67 years) started a course of non-surgical periodontal treatment. Clinical indices were measured at 2 periodontitis sites at the initial visit and at 8 weeks after the completion of treatment in each subject. A 30-s sample of GCF was collected from each test site using perio paper strips. Each strip was placed into 500 microl of ice cold 0.1 M PBS, pH 7.4, vortex mixed for 30 s, and then stored at -70 degrees C until analysed by radioimmunoassay. RESULTS: The clinical condition of all test sites improved as a result of the periodontal treatment. The levels (pg/30 s sample) of SP fell from 56.3 (SD 66.0) at the initial visit to 4.2 (3.1) after treatment, p=0.017. The concentration (pg/microl) of SP in GCF fell from 140.6 (175.6) to 24.2 (11.1), p=0.036. The levels of NKA fell from 30.5 (17.1) to 10.6 (4.9), p=0.012 whereas the concentration changed little from 85.4 (43.5) to 61.6 (15.1), p=0.41. CONCLUSION: The reduction in inflammation resulting from effective periodontal treatment is associated with a reduction in the levels of tachykinins in gingival crevicular fluid.

The calcium channel blocker used with cyclosporin has an effect on gingival overgrowth.

BACKGROUND/AIMS: To investigate whether the choice of calcium channel blocker, used in conjunction with cyclosporin A, affected the prevalence of gingival overgrowth. METHOD: A cohort of 135 renal transplant recipients who had been medicated with cyclosporin A in combination with either nifedipine (89) or amlodipine (46) since transplant, took part in the study. The inclusion criteria were that eligible subjects had been in receipt of a kidney transplant for at least 12 months, had at least 10 teeth and had not received specialist periodontal treatment. The age, gender, current drug regimen and dosage were recorded for each participant and alginate impressions taken of both arches. The presence and severity of gingival overgrowth were scored from plaster models. RESULTS: A higher proportion (72%) of the amlodipine group were categorised as having gingival overgrowth compared with only 53% of the nifedipine group, chi square=4.5, p<0.05. Logistic regression analysis was used to explore the relationship between the presence or absence of gingival overgrowth (dependent variable) and age, gender, time since transplant, dose of cyclosporin A, centre in which the patient was treated, and the calcium channel blocker used (independent variables). Independent predictors of gingival overgrowth in this multivariate analysis were whether the individual was treated with amlodipine or nifedipine (p=0.01) and whether the individual was young or old (p=0.01). Within the multivariate analysis, the odds ratio for amlodipine to be associated with gingival overgrowth compared with nifedipine was 3.0 (confidence interval 1.3-6.9). CONCLUSIONS: The prevalence of gingival overgrowth in renal transplant recipients maintained on cyclosporin A and nifedipine is lower than those treated with cyclosporin A and amlodipine.