Pierre C. Baehni

Porphyromonas gingivalis Gingipain-R Enhances Interleukin-8 but Decreases Gamma Interferon-Inducible Protein 10 Production by Human Gingival Fibroblasts in Response to T-Cell Contact

ABSTRACT Proteases produced by Porphyromonas gingivalis, an oral pathogen, are considered important virulence factors and may affect the responses of cells equipped with proteinase-activated receptors. The aim of this study was to investigate the effect of the arginine-specific cysteine protease gingipain-R produced by P. gingivalis on chemokine production by human gingival fibroblasts (HGF) and the effect of gingipain-R treatment on the subsequent contact-dependent activation of HGF by T cells. HGF incubated in the presence of purified 47-kDa gingipain-R showed increased levels of interleukin-8 (IL-8) mRNA. Cyclooxygenase-2 (COX-2) mRNA was also induced. Further exposure of HGF to activated T cells resulted in the dose- and time-dependent enhancement of IL-8 transcription and release. T-cell membrane-bound tumor necrosis factor (TNF) was the ligand inducing IL-8 production by HGF, since TNF neutralization abrogated HGF responses to T-cell contact. The enhanced IL-8 release was due, at least in part, to prostaglandin-E2production, which was mostly blocked by indomethacin. Gingipain-R proteolytic activity was required since heat inactivation, specific synthetic protease inhibitors, and the natural substrate competitor histatin 5 abrogated its effects. The enhanced production of IL-8 in response to T-cell contact was specific since monocyte chemotactic protein-1 (MCP-1) production was unaffected while interferon-gamma-inducible protein-10 (IP-10) was inhibited. The sum of these activities may result in the recruitment of differential cell types to sites of inflammation since IL-8 preferentially recruits neutrophils and IP-10 attracts activated T cells and may be relevant to the pathogenesis of periodontitis.

Current status in oral fluoride pharmacokinetics and implications for the prophylaxis against dental caries

Fluoride plays a central role in the prevention of dental caries. There is evidence that its effect is mainly topical and that continuous presence of fluoride ions in low concentration at the plaque/enamel interface is essential. The present paper reviews the most important aspects of fluoride kinetics in the oral cavity and discusses their implications on preventive approaches to dental caries. As a continuous presence of fluoride ions in saliva is important for an optimum prophylactic effect, new formulations capable of delivering low levels of fluoride over prolonged periods of time have been developed. These systems consist either of intra-oral devices, or of restorative materials into which fluoride has been incorporated. Among all the preparations investigated, bioadhesive tablets and membrane-controlled reservoirs are the most promising.

Development and applications of injectable poly(ortho esters) for pain control and periodontal treatment.

Poly(ortho esters) with a low glass transition temperature are semi-solid materials so that therapeutic agents can be incorporated at room temperature, without the use of solvents, by a simple mixing procedure. When molecular weights are limited to < 5 kDa, such materials are directly injectable using a needle size no larger than 22 gauge. Somewhat hydrophilic polymers can be produced by using the diketene acetal 3,9-diethylidene-2,4,8,10-tetraoxaspiro[5.5]undecane and triethylene glycol (TEG), while hydrophobic materials can be produced by using the diketene acetal and 1,10-decanediol. Molecular weight can be reproducibly controlled by using an excess of the diol, or by use of an alcohol that acts as a chain-stopper. Erosion rates can be controlled by varying the amount of latent acid incorporated into the polymer backbone. Toxicology studies using the TEG polymer have been completed and have shown that the polymer is non-toxic. Toxicology studies using the decanediol polymer are underway. Development studies using the TEG polymer aimed at providing a sustained delivery of an analgesic agent to control post-surgical pain are under development and human clinical trials using the decanediol polymer for the treatment of periodontitis are also underway.

Bioerodible Injectable Poly(ortho ester) for Tetracycline Controlled Delivery to Periodontal Pockets: Preliminary Trial in Humans

The semisolid consistency of poly(ortho esters) (POEs) containing tetracycline free base allows direct injection in the periodontal pocket and shows sustained and almost constant in vitro release in phosphate buffer, pH 7.4 at 37°C, for up to 14 days. Total polymer degradation concomitant with drug release was obtained. Formulations containing 10% or 20% (wt/wt) tetracycline were evaluated in a panel of 12 patients suffering from severe and recurrent periodontitis. In the first trial including 6 patients, single-rooted teeth and molar teeth with furcations were treated immediately after scaling and root planing. Patients tolerated both formulations well, experienced no pain during application, and showed no signs of irritation or discomfort during the observation period. However, retention of the formulation was minimal in this first study. An improved clinical protocol followed in the second study (stopping bleeding after scaling and root planning) prolonged the retention of the formulations in the inflamed periodontal pockets. For up to 11 days, tetracycline concentrations in the gingival crevicular fluid were higher than the minimum inhibitory concentration of tetracycline against most periodontal pathogens.

Caries prevalence and associated predisposing conditions in recently hospitalized elderly persons

The prevalence of caries and caries risk factors was studied among 120 consecutively hospitalized elderly persons. Coronal caries was recorded using the WHO criteria, and active and inactive root caries in accordance with Fejerskov et al. The CPITN was used to evaluate the periodontal state and plaque accumulation in accordance with Löe & Silness. Of the 1212 teeth examined 5% had active coronal caries (2% inactive), 14% active root caries (2% inactive), and 10% fillings with recurrent caries. No relationship was found between caries prevalence, degree of dependence, number of medicaments, age, and gender. Patients with psychiatric diseases had increased caries prevalence (P < 0.01), and lower caries prevalence was associated with frequent tooth brushing (P < 0.05). At the tooth level root caries was associated with high plaque scores (P < 0.001), degree of gingival recession (P < 0.001), presence of coronal caries (P < 0.001), and increased pocket depth (P < 0.01). The results strongly indicate that oral hygiene measures should be introduced immediately after hospitalization of these patients.

Salivary fluoride concentrations following applications of bioadhesive tablets and mouthrinses

Presence of elevated fluoride concentration in saliva is important for the prevention of caries. In the present study, we developed an intra-oral bioadhesive tablet aimed at delivering F(-) in the mouth over a prolonged period of time. Various tablet formulations were tested in vivo for their tolerance and adhesiveness. Two formulations were selected for further studies on salivary fluoride clearance. For comparison, mouthrinses with increasing F(-) concentrations were also examined. Results indicate that a bioadhesive tablet located on the upper gingiva is able to sustain salivary F(-) concentrations for about 10h without major side effects. Mouthrinses with high F(-) concentration were able to prolong salivary fluoride retention for more than 6h.

Association between early preterm birth and periodontitis according to USA and European consensus definitions

Objective: Prospective case–control study assessing the association between maternal periodontitis according to the recently issued USA and European consensus definitions and early preterm delivery (<35 weeks gestation). Cases were women delivering between 22 and 346/7 weeks of gestation (n = 84) and controls were women delivering at term (≥37 weeks) (n = 345). Methods: Periodontal examination at the immediate postpartum period identified periodontitis according to both consensus definitions. A multivariate logistic model was used to assess the association between early preterm delivery and the presence of periodontitis adjusted for confounders. Results: All women had periodontitis by the European consensus definitions. When using the USA definitions, more cases had severe periodontitis than controls (34.5% vs. 17.72%); p = 0.003. After adjustment for main confounders, the association between severe (OR: 2.38; 95% CI: 1.36–4.14) periodontitis and early preterm delivery persisted. The only other independent factor associated with early preterm delivery was vaginal bleeding during pregnancy. Conclusions: Early preterm delivery is associated with periodontitis when the USA consensus definitions are used. The European definitions revealed inadequate for the study population because of the lack of discrimination power.