Interleukin-1 receptor signaling rather than that of tumor necrosis factor is critical in protecting the host from the severe consequences of a polymicrobe anaerobic infection.
Infection of the dental pulp leads to an osteolytic lesion that results from a polymicrobial infection consisting largely of pathogenic anaerobes. Infection causes significant morbidity and mortality mediated by bacterial factors and in some cases by the up-regulation of inflammatory cytokines. The inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor (TNF), in particular, play a complex and central role in the responses to microbial pathogens. However, relatively little is known about the significance of these cytokines in protecting the host from focal polymicrobial anaerobic infections. To establish the relative importance of IL-1 and TNF in mediating the response to a mixed anaerobic infection, we inoculated the dental pulp of mice with six anaerobic pathogens containing functional deletions of receptors to IL-1 (IL-1R1(-/-)), TNF (TNFRp55(-/-)-p75(-/-)), or both (TNFRp55(-/-)-IL-1RI(-/-)). The results indicate that IL-1 receptor signaling and TNF receptor signaling both play similarly important roles in protecting the host from local tissue damage. However, IL-1 receptor signaling is considerably more important than TNF receptor signaling in preventing the spread of infection into surrounding fascial planes, since IL-1R1(-/-) but not TNFRp55(-/-)-p75(-/-) mice exhibited significantly higher morbidity and mortality. Moreover, all of the fatal infections occurred in male mice, suggesting the importance of gender differences in limiting the impact of these infections. (+info)
Developing an index of restorative dental treatment need.
The process undertaken to establish an initial pilot index for restorative dental treatment is described. Following consultation with a wide range of clinicians and others, an outline framework for the index was developed and comprised three main components: 1. Patient identified need for treatment: the data from the patient perceived need questionnaire were inconclusive; 2. Complexity of treatment (assessed by clinicians): this was found to be a practical tool capable of being used by a range of dentists. A booklet has been produced which describes the process of using the scoring system; 3. Priority for treatment (assessed by clinicians): three levels of priority were identified; the highest priority was assigned to patients with inherited or developmental defects that justify complex care (eg clefts of the lip and palate). The initial development of the index has had some success in a difficult area. The treatment complexity component is the most developed and may allow both referrers and commissioners of specialist restorative dentistry to determine appropriate use of skilled clinicians' expertise. (+info)
Molecular identification of microorganisms from endodontic infections.
A relatively wide range of bacteria have been isolated from root canals using standard culture techniques. However, only 50% of the bacteria in the oral cavity are cultivable (S. S. Socransky et al., Arch. Oral Biol. 8:278-280, 1963); hence, bacterial diversity in endodontic infections is underestimated. This study used a PCR-based 16S rRNA gene assay, followed by cloning and sequencing of 16S rRNA amplicons from a small subset of samples to assess the diversity of bacteria present in infected root canals. A total of 41 clinical samples from 15 de novo and 26 refractory cases of endodontic infections were assessed. Of these samples, 44% were positive by culture and 68% were positive by PCR. Eight samples were selected for further analysis. Of these, the two de novo cases yielded sequences related to those of the genera Enterococcus, Lactobacillus, Propionibacterium, and Streptococcus and two clones were related to previously uncultivated bacteria, while the sinus-associated, de novo case yielded sequences related to those of the genera Lactobacillus, Pantoea, Prevotella, and Selenomonas. The five refractory cases produced clones which were related to the genera Capnocytophaga, Cytophaga, Dialister, Eubacterium, Fusobacterium, Gemella, Mogibacterium, Peptostreptococcus, Prevotella, Propionibacterium, Selenomonas, Solobacterium, Streptococcus, and Veillonella and two clones representing previously uncultivated bacteria. The phylogenetic positions of several clones associated with the Clostridiaceae and Sporomusa subgroups of the Firmicutes grouping are also shown. This study demonstrates that molecular techniques can detect the presence of bacteria in endodontic infections when culture techniques yield a negative result and can be used to identify a wider range of endodontic-infection-related bacteria including the presence of previously unidentified or unculturable bacteria. (+info)
Diabetes mellitus as a modulating factor of endodontic infections.
Diabetes mellitus is a chronic disease with serious health consequences. The association between diabetes and periodontal disease is well documented. However, the progression and healing of endodontic infections in diabetic patients has not been adequately studied. In this review, diabetes mellitus is explored as a potential modulating factor of endodontic pathosis. Recent data on the relationship between the clinical presentation of pulpal and periradicular disease, as well as the outcome of endodontic treatment in diabetic and nondiabetic patients, are presented. Diabetics who present for endodontic treatment, particularly those with periradicular pathosis, may have increased perioperative symptoms. Cases with preoperative periradicular lesions are less likely to be determined successful two years or longer postoperatively if the patient reports a history of diabetes. Studies examining the pathogenesis of periradicular lesions in mouse models with uncontrolled type 1 diabetes suggest that the lesion size may be increased and the animals have increased serious sequelae. Preliminary findings suggest that some bacterial species may be more prevalent in necrotic pulp of diabetic than nondiabetic patients. More studies are needed to further explore the microbiology of endodontic infections and to determine effective treatment strategies in both diabetic and nondiabetic patients. (+info)
Vitality of the dentin-pulp complex in health and disease: growth factors as key mediators.
The vitality of the dentin-pulp complex, both during tissue homeostasis and after injury, is dependent on pulp cell activity and the signalling processes, which regulate the behavior of these cells. Research, particularly over the last ten to fifteen years, has led to a better understanding of the molecular control of cellular behavior. Growth factors play a pivotal role in signalling the events of tissue formation and repair in the dentin-pulp complex. Sequestration of growth factors in the dentin matrix during tissue formation provides a pool of these molecules, which may be released during injury and contribute to signalling of reparative events. Therapeutic intervention with recombinant growth factors also provides possibilities for control of cell activity during repair. Harnessing both endogenous and exogenous sources of growth factors can provide exciting opportunities for novel biological approaches to dental tissue repair and the blueprint for tissue engineering of the tooth. These approaches offer significant potential for improved clinical management of dental disease and maintenance of tooth vitality. (+info)
Gamma interferon (IFN-gamma) and IFN-gamma-inducing cytokines interleukin-12 (IL-12) and IL-18 do not augment infection-stimulated bone resorption in vivo.
Periapical granulomas are induced by bacterial infection of the dental pulp and result in destruction of the surrounding alveolar bone. In previous studies we have reported that the bone resorption in this model is primarily mediated by macrophage-expressed interleukin-1 (IL-1). The expression and activity of IL-1 is in turn modulated by a network of Th1 and Th2 regulatory cytokines. In the present study, the functional roles of the Th1 cytokine gamma interferon (IFN-gamma) and IFN-gamma-inducing cytokines IL-12 and IL-18 were determined in a murine model of periapical bone destruction. IL-12-/-, IL-18-/-, and IFN-gamma-/- mice were subjected to surgical pulp exposure and infection with a mixture of four endodontic pathogens, and bone destruction was determined by microcomputed tomography on day 21. The results indicated that all IL-12-/-, IL-18-/-, and IFN-gamma-/- mice had similar infection-stimulated bone resorption in vivo as wild-type control mice. Mice infused with recombinant IL-12 also had resorption similar to controls. IFN-gamma-/- mice exhibited significant elevations in IL-6, IL-10, IL-12, and tumor necrosis factor alpha in lesions compared to wild-type mice, but these modulations had no net effect on IL-1alpha levels. Recombinant IL-12, IL-18, and IFN-gamma individually failed to consistently modulate macrophage IL-1alpha production in vitro. We conclude that, at least individually, endogenous IL-12, IL-18, and IFN-gamma do not have a significant effect on the pathogenesis of infection-stimulated bone resorption in vivo, suggesting possible functional redundancy in proinflammatory pathways. (+info)
Virulence factors of Enterococcus faecalis: relationship to endodontic disease.
Enterococcus faecalis is a micro-organism that can survive extreme challenges. Its pathogenicity ranges from life-threatening diseases in compromised individuals to less severe conditions, such as infection of obturated root canals with chronic apical periodontitis. In the latter situation, the infecting organisms are partly shielded from the defense mechanisms of the body. In this article, we review the virulence factors of E. faecalis that may be related to endodontic infection and the periradicular inflammatory response. The most-cited virulence factors are aggregation substance, surface adhesins, sex pheromones, lipoteichoic acid, extracellular superoxide production, the lytic enzymes gelatinase and hyaluronidase, and the toxin cytolysin. Each of them may be associated with various stages of an endodontic infection as well as with periapical inflammation. While some products of the bacterium may be directly linked to damage of the periradicular tissues, a large part of the tissue damage is probably mediated by the host response to the bacterium and its products. (+info)
Uncultivated phylotypes and newly named species associated with primary and persistent endodontic infections.
Endodontic infections have been traditionally studied by culture methods, but recent reports showing that over 50% of the oral microbiota is still uncultivable (B. J. Paster et al., J. Bacteriol. 183:3770-3783, 2001) raise the possibility that many endodontic pathogens remain unknown. This study intended to investigate the prevalence of several uncultivated oral phylotypes, as well as newly named species in primary or persistent endodontic infections associated with chronic periradicular diseases. Samples were taken from the root canals of 21 untreated teeth and 22 root-filled teeth, all of them with radiographic evidence of periradicular bone destruction. Genomic DNA was isolated directly from each sample, and 16S rRNA gene-based nested or heminested PCR assays were used to determine the presence of 13 species or phylotypes of bacteria. Species-specific primers had already been validated in the literature or were developed by aligning closely related 16S rRNA gene sequences. Species specificity for each primer pair was confirmed by running PCRs against a panel of several oral bacteria and by sequencing DNA from representative positive samples. All species or phylotypes were detected in at least one case of primary infections. The most prevalent species or phylotypes found in primary infections were Dialister invisus (81%), Synergistes oral clone BA121 (33%), and Olsenella uli (33%). Of the target bacteria, only these three species were detected in persistent infections. Detection of uncultivated phylotypes and newly named species in infected root canals suggests that there are previously unrecognized bacteria that may play a role in the pathogenesis of periradicular diseases. (+info)