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.

The lifetime direct cost of periodontal treatment:A case study from a norwegian specialist practice

Background: Successful periodontal treatment requires a commitment to regular lifelong maintenance and may be perceived by patients to be costly. This study calculates the total lifetime cost of periodontal treatment in the setting of a specialist periodontal practice and investigates the cost implications of choosing not to proceed with such treatment. Methods: Data from patients treated in a specialist practice in Norway were used to calculate the total lifetime cost of periodontal treatment that included baseline periodontal treatment, regular maintenance, retreatment, and replacing teeth lost during maintenance. Incremental costs for alternative strategies based on opting to forego periodontal treatment or maintenance and to replace any teeth lost with either bridgework or implants were calculated. Results: Patients who completed baseline periodontal treatment but did not have any additional maintenance or retreatment could replace only three teeth with bridgework or two teeth with implants before the cost of replacing additional teeth would exceed the cost of lifetime periodontal treatment. Patients who did not have any periodontal treatment could replace ≤4 teeth with bridgework or implants before a replacement strategy became more expensive. Conclusions: Within the limits of the assumptions made, periodontal treatment in a Norwegian specialist periodontal practice is cost-effective when compared to an approach that relies on opting to replace teeth lost as a result of progressive periodontitis with fixed restorations. In particular, patients who have initial comprehensive periodontal treatment but do not subsequently comply with maintenance could, on average, replace ≤3 teeth with bridgework or two teeth with implants before this approach would exceed the direct cost of lifetime periodontal treatment in the setting of the specialist practice studied. © 2012 American Academy of Periodontology.

Incorporating Severity and Risk as Factors to the Fardal Cost-Effectiveness Model to Create a Cost-Benefit Model for Periodontal Treatment

Background: A previously described economic model was based on average values for patients diagnosed with chronic periodontitis (CP). However, tooth loss varies among treated patients and factors for tooth loss include CP severity and risk. The model was refined to incorporate CP severity and risk to determine the cost of treating a specific level of CP severity and risk that is associated with the benefit of tooth preservation.

Methods: A population that received and another that did not receive periodontal treatment were used to determine treatment costs and tooth loss. The number of teeth preserved was the difference of the number of teeth lost between the two populations. The cost of periodontal treatment was divided by the number of teeth preserved for combinations of CP severity and risk.

Results: The cost of periodontal treatment divided by the number of teeth preserved ranged from (US) $ 1,405 to $ 4,895 for high or moderate risk combined with any severity of CP and was more than $ 8,639 for low risk combined with mild CP. The cost of a three-unit bridge was $ 3,416, and the cost of a single-tooth replacement was $ 4,787.

Conclusion: Periodontal treatment could be justified on the sole basis of tooth preservation when CP risk is moderate or high regardless of disease severity.

Periodontal Manifestations of Chronic Atypical Neutrophilic Dermatosis With Lipodystrophy and Elevated Temperature (CANDLE) Syndrome in an 11 Year Old Patient

Introduction: Chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) is an auto inflammatory syndrome caused by an autosomal recessive gene mutation. This very rare syndrome has been reported in only 14 patients worldwide. A number of clinical signs have been reported including joint contractures, muscle atrophy, microcytic anaemia, and panniculitis-induced childhood lipodystrophy. Further symptoms include recurrent fevers, purpuric skin lesions, periorbital erythema and failure to thrive. This is the first reported case of periodontal manifestations associated with CANDLE syndrome. 
Case Presentation: An 11 year old boy was referred to Cork University Dental School and Hospital with evidence of severe periodontal destruction. The patient’s medical condition was managed in Great Ormond Street Children’s Hospital, London. The patient’s dental management included initial treatment to remove teeth of hopeless prognosis followed by prosthodontic rehabilitation using removable partial dentures. This was followed by further non-surgical periodontal treatment and maintenance. In the long term, the potential definitive restorative options, including dental implants, will be evaluated in discussion with the patient’s medical team.
Conclusion: Periodontitis as a manifestation of systemic disease is one of seven categories of periodontitis as defined by the American Academy of Periodontology 1999 classification system. A number of systemic diseases have been associated with advanced periodontal destruction including Diabetes Mellitus, Leukaemia and Papillon-Lefevre Syndrome. In the case described, treatment necessitated a multidisciplinary approach with input from medical and dental specialities for a young patient with severe periodontal destruction associated with CANDLE syndrome.

LL-37 quantification in gingival crevicular fluid (GCF) from periodontitis patients

Background: LL-37, an anti-microbial peptide belonging to the cathelicidin family, derives its name from two N-terminal leucine residues and the 37 amino acids comprising the peptide. LL-37 is the only known cathelicidin to exist in humans. It exhibits both anti-bacterial and immunomodulatory properties. Objectives: In the current study, LL-37 was quantified in GCF from periodontitis patients. Previous studies have relied on qualitative results from Western blotting to detect LL-37 in GCF. This study aims to quantitatively determine LL-37 levels in GCF. Methods: GCF and bacterial plaque samples, pre- and post non-surgical periodontal treatment, were collected from 4 sites in 12 patients presenting with advanced periodontitis. Plaque samples were analysed by QPCR for the presence or absence of the periodontopathic bacterium Porphyromonas gingivalis (P. gingivalis). The concentrations of LL-37 in patient samples pre- and post-treatment were deduced by indirect enzyme linked immunosorbent assay (ELISA). Results: Concentrations of LL-37 in samples varied between a minimum and maximum of 1 and 40 ng/ml. LL-37 levels were shown, pre-treatment, to be higher in deep pockets (6-9 mm) compared with shallower pockets (3-5 mm) and highest in those sites which were positive for P. gingivalis. Non-surgical therapy resulted in a significant improvement in clinical indices while expression levels of P. gingivalis were reduced. Following treatment, LL-37 levels in GCF decreased from an average of 6.5 ± 1 - 5.8 ± 1.2 ng/ml. The most interesting observation however was the reduction in LL-37 levels, from an average of 7 ± 1.3 – 2.5 ± 1.1 ng/ml in those sites where P. gingivalis infection was eradicated post-treatment. Conclusions: LL-37 levels are increased at sites showing advanced periodontal disease, reduce following treatment and appear to be linked to the presence of P. gingivalis. This study will further our knowledge of host defence in chronic diseases such as periodontitis.

LL-37 Degradation by GCF: A Role for Porphyromonas gingivalis Proteinases?

Background: LL-37, composed of 37 amino acid residues, is an innate host defence peptide of the cathelicidin family. It is expressed by neutrophils, monocytes and epithelial cells and exhibits both anti-bacterial and immunomodulatory properties. LL-37 is however prone to proteolytic degradation by proteinases, thus potentially limiting its inherent host defence properties in the inflammatory milieu. Objectives: The present study was designed to determine whether LL-37 was degraded by components of gingival crevicular fluid (GCF) from healthy subjects or those with periodontitis. In addition, we aimed to deduce whether degradation of the peptide was accelerated in GCF samples which were determined to be positive for the periodontopathic bacterium Porphyromonas gingivalis. Methods: GCF and bacterial plaque samples, pre- and post non-surgical periodontal treatment, were collected from 4 individual sites in patients presenting with advanced periodontitis. In healthy subjects, GCF samples only were collected. Plaque samples were analysed by QPCR for the presence or absence of P. gingivalis. Pooled GCF samples from healthy sites; periodontitis sites which were P. gingivalis negative (Pg-); or periodontitis sites which were P. gingivalis positive (Pg+), were incubated with synthetic LL-37 for 0 – 180 min. The degradation products were then analysed by matrix-assisted laser desorption/ionisation time of flight mass spectrometry (MALDI-TOF MS). Results: LL-37 was not degraded when incubated with GCF from healthy subjects. In contrast, LL-37 was degraded after 30 min when incubated with Pg- GCF. However degradation of LL-37 was apparent after only 2 min incubation with Pg+ GCF and the parent molecule was almost completely degraded after 30 min. Conclusions: The rapid degradation of LL-37, particularly in Pg+ sites, highlights the limited role which this host defence peptide may play in the presence of biologically active proteinases. It also underscores a potent virulence mechanism of P. gingivalis used to circumvent innate host responses.

Tooth loss and implant outcomes in patients refractory to treatment in a periodontal practice

Aim: The aim of this study was to investigate the factors associated with continued significant tooth loss due to periodontal reasons during maintenance following periodontal therapy in a specialist periodontal practice in Norway.
Material and Methods: A case-control design was used. Refractory cases were patients who lost multiple teeth during a maintenance period of 13.4 (range 8-19) years following definitive periodontal treatment in a specialist practice. Controls were age- and gender-matched maintenance patients from the same practice. Characteristics and treatment outcomes were assessed, and all teeth classified as being lost due to periodontal disease during follow-up were identified. The use of implants in refractory cases and any complications relating to such a treatment were recorded.
Results: Only 27 (2.2%) patients who received periodontal treatment between 1986 and 1998 in a specialist practice met the criteria for inclusion in the refractory to treatment group. Each refractory subject lost 10.4 (range 4-16) teeth, which represented 50% of the teeth present at baseline. The rate of tooth loss in the refractory group was 0.78 teeth per year, which was 35 times greater than that in the control group. Multivariate analysis indicated that being in the refractory group was predicted by heavy smoking (p=0.026), being stressed (p=0.016) or having a family history of periodontitis (p=0.002). Implants were placed in 14 of the refractory patients and nine (64%) of these lost at least one implant. In total, 17 (25%) of the implants placed in the refractory group were lost during the study period.
Conclusions: A small number of periodontal maintenance patients are refractive to treatment and go on to experience significant tooth loss. These subjects also have a high level of implant complications and failure. Heavy smoking, stress and a family history of periodontal disease were identified as factors associated with a refractory outcome.

Caseinolytic activity in gingival crevicular fluid from periodontitis patients

Introduction: Protease activity is essential for the progression of periodontal disease and several studies have shown that gingival crevicular fluid (GCF) proteases are associated with the attachment loss and bone destruction associated with periodontial disease. In addition to measuring protease levels using ELISA, it is also important to consider enzyme activity which can be measured using appropriate substrates. Aim: The aim of this work was to measure the proteolyitc activity in gingival crevicular fluid (GCF) from periodontitis patients using zymography and a fluorogenic protease substrate. Materials and Methods: Twenty four GCF samples were collected from patients with established periodontitis who had not received any periodontal treatment in the previous six months. A strip of perio-paper was inserted into the gingival crevice until light resistance was felt. After 30 seconds the perio-paper was removed and placed into 500 ul ice cold 0.01M sodium phosphate buffer, pH 7.2, containing 0.15M sodium chloride, vortex mixed for 30 seconds and stored at -80°C until required. GCF samples (10 ul) were electrophoresed on 4-16% Blue casein zymogram gels at 125V constant voltage for 90 min. Following electrophoresis the gel was washed in renaturation buffer for 30 min and then placed in developing buffer overnight. Areas of protease activity appeared as clear bands against a blue background. The total caseinolytic activity of each GCF sample was measured using a fluorescent assay with resorufin-labelled casein as the substrate. Results: The results showed that both casein zymography and fluorogenic assay methods were suitable for analysing caseinolytic activity in GCF samples from periodontitis patients. Caseinolytic activity was variable in the periodontitis samples studied and may reflect the episodic nature of the disease. Conclusion: Casein zymography and fluorogenic assay methods may be useful in future attempts to measure active episodes of periodontal disease.

Formulation and characterisation of tetracycline-containing bioadhesive polymer networks designed for the treatment of periodontal disease.

This study described the drug release, rheological (dynamic and flow) and textural/mechanical properties of a series of formulations composed of 15% w/w polymethylvinylether-co-maleic anhydride (PMVE-MA), 0-9% w/w polyvinylpyrrolidone (PVP) and containing 1-5% w/w tetracycline hydrochloride, designed for the treatment of periodontal disease. All formulations exhibited pseudoplastic flow with minimal thixotropy. Increasing the concentration of PVP sequentially increased the zero-rate viscosity (derived from the Cross model) and the hardness and compressibility of the formulations (derived from texture profile analysis). These affects may be accredited to increased polymer entanglement and, in light of the observed synergy between the two polymers with respect to their textural and rheological properties, interaction between PVP and PMVE-MA. Increasing the concentration of PVP increased the storage and loss moduli yet decreased the loss tangent of all formulations, indicative of increased elastic behaviour. Synergy between the two polymers with respect to their viscoelastic properties was observed. Increased adhesiveness, associated with increased concentrations of PVP was ascribed to the increasing bioadhesion and tack of the formulations. The effect of increasing drug concentration on the rheological and textural properties was dependent on PVP concentration. At lower concentrations (0, 3% w/w) no effect was observed whereas, in the presence of 9% w/w PVP, increasing drug concentration increased formulation elasticity, zero rate viscosity, hardness and compressibility. These observations were ascribed to the greater mass of suspended drug in formulations containing the highest concentration of PVP. Drug release from formulations containing 6 and 9% PVP (and 5% w/w drug) was prolonged and swelling/diffusion controlled. Based on the drug release, rheological and textural properties, it is suggested that the formulation containing 15% w/w PMVE-MA, 6% w/w PVP and tetracycline hydrochloride (5% w/w) may be useful for the treatment of periodontal disease.