Inflammatory Response Mechanisms of the Dentine-Pulp Complex and the Periapical Tissues.

The macroscopic and microscopic anatomy of the oral cavity is complex and unique in the human body. Soft-tissue structures are in close interaction with mineralized bone, but also dentine, cementum and enamel of our teeth. These are exposed to intense mechanical and chemical stress as well as to dense microbiologic colonization. Teeth are susceptible to damage, most commonly to caries, where microorganisms from the oral cavity degrade the mineralized tissues of enamel and dentine and invade the soft connective tissue at the core, the dental pulp. However, the pulp is well-equipped to sense and fend off bacteria and their products and mounts various and intricate defense mechanisms. The front rank is formed by a layer of odontoblasts, which line the pulp chamber towards the dentine. These highly specialized cells not only form mineralized tissue but exert important functions as barrier cells. They recognize pathogens early in the process, secrete antibacterial compounds and neutralize bacterial toxins, initiate the immune response and alert other key players of the host defense. As bacteria get closer to the pulp, additional cell types of the pulp, including fibroblasts, stem and immune cells, but also vascular and neuronal networks, contribute with a variety of distinct defense mechanisms, and inflammatory response mechanisms are critical for tissue homeostasis. Still, without therapeutic intervention, a deep carious lesion may lead to tissue necrosis, which allows bacteria to populate the root canal system and invade the periradicular bone via the apical foramen at the root tip. The periodontal tissues and alveolar bone react to the insult with an inflammatory response, most commonly by the formation of an apical granuloma. Healing can occur after pathogen removal, which is achieved by disinfection and obturation of the pulp space by root canal treatment. This review highlights the various mechanisms of pathogen recognition and defense of dental pulp cells and periradicular tissues, explains the different cell types involved in the immune response and discusses the mechanisms of healing and repair, pointing out the close links between inflammation and regeneration as well as between inflammation and potential malignant transformation.

[The radicular cyst in the maxillary sinus encountered in the clinical otorhinolaryngological practice]. / Radikuliarnaia kista verkhnei cheliusti v praktike otorinolaringologa.

This article was designed to report the clinical case of the radicular cyst localized in the maxillary sinus of the 23 year-old man that had been detected before the surgical intervention was undertaken for its treatment. In the preceding visits of the patient to other medical settings, this condition was misinterpreted as a genuine (rhinogenic) cyst. It accounted for the choice of the inadequate surgical strategy for the management of this pathology. As a result, the patient experienced two relapse episodes of the disease. The thorough analysis of the patient's medical history and CT images of the sinus obtained during the 4 year follow up period allowed to establish the definitive diagnosis of odontogenic cyst of the upper jaw. The authors present a brief overview of the relevant scientific literature concerning etiology and pathogenesis as well as the methods of diagnostics and treatment of radicular cyst of the upper jaw.

Possible role of apoptosis in the pathogenesis and clinical evolution of radicular cyst: an immunohistochemical study.

AIM: To investigate whether the apoptotic cascade is activated through the extrinsic pathway in epithelial lining and connective tissue of radicular cysts. METHODOLOGY: Fifteen radicular cysts were fixed in formalin, embedded in paraffin wax and processed for immunohistochemistry to evaluate the expression of polyclonal antibodies against Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), DR5 and caspase-3. Immunocomplexes were treated with the secondary antibodies and finally detected using the avidin-biotin-peroxidase complex. Immunoreactivity was visualized by development with 3,3'-diaminobenzidine. Data were analysed using the Mann-Whitney U-test; P < 0.05 was considered significant. RESULTS: The three antibodies were detected in connective tissue fibroblasts of all radicular cysts; TRAIL and DR5 immunoexpression was significantly greater (P < 0.05) compared with that of caspase-3. The three antibodies were also expressed in almost all epithelial layers and in endothelial cells of newly formed vessels. CONCLUSION: The involvement of apoptosis in the pathogenesis of radicular cysts, demonstrated by the immunoexpression patterns of TRAIL, DR5 and caspase-3 in lining epithelium and connective tissue, may explain their bland clinical aggressiveness and slow, benign evolution.

Can traumatic occlusion cause endodontic problems? A case report.

Radicular cysts are commonly found odontogenic cysts in the jaws. The lesion is diagnosed mainly in young patients during the second decade of life. In the majority of cases, it is asymptomatic. This paper reports a rare case in which traumatic occlusion was identified as the etiology of a radicular cyst. Endodontic treatment was performed and the traumatic occlusion also was corrected. A six-month follow-up appointment found good healing of the periapical region.

Role of interleukin-1 in pathogenesis of radicular cyst.

BACKGROUND: Interleukin-1 (IL-1) is one of the cytokines produced by macrophages, monocytes and dentritc cells. Macrophages are present in apical granuloma and the wall of the radicular cyst. This cytokine causes the cyst expansion and is involved in proliferation of fibroblasts in the cyst wall and stimulate the fibroblasts to produce more prostaglandin. Radicular cyst is the most common cyst of the jaws which is usually associated with necrotic pulp of the tooth. The cyst formation requires proliferation of the epithelial rest cells of Malassez present in the periodontal ligament. Proliferation of epithelial rest cells of Malassez is an essential event in the Pathogenesis of radicular cyst. Objective of the study was to investigate the effect of IL-1 on epithelial cell proliferation which is an important factor in the pathogenesis of radicular cyst. METHODS: The cyst walls of 20 radicular cysts were removed and were cultured in vitro to grow the epithelial cells. The culture were rapidly contaminated and dominated by growth of fibroblasts. Therefore another cell line was used for the experiments. RESULTS: The result showed that proliferation was stimulated with increased in a biphasic manner with maximum stimulation at 1.25 nanog/ml, beyond this concentration proliferation was decreased. CONCLUSION: IL-1 had a proliferative effect on epithelial cells at low concentrations which may be playing a role in evoking an inflammatory reaction and stimulating the epithelial cell rests of Malassez to proliferate to form radicular cyst.

Histopathological profile of surgically removed persistent periapical radiolucent lesions of endodontic origin.

AIM: To determine the types of periapical lesions associated with root filled teeth with persistent periapical pathosis that required surgical treatment based on specific inclusion and exclusion criteria. METHODOLOGY: Periapical lesions from a consecutive clinical sample of 100 patients were examined histopathologically to determine a definitive diagnosis. RESULTS: Females were more represented (n = 56), the average age was 46.5 years and there were no age differences between gender or lesion type. A diagnosis of periapical granuloma was the most common finding with a similar number present in females (n = 40) and males (n = 37). A cyst was present in 18% of the cases with a majority of females (n = 12) represented in the sample. Evidence of foreign material, with an appearance consistent with endodontic sealer materials, was seen in 25 periapical granulomas, two cysts and one scar. Two periapical scars were seen, one had a history of apicectomy and amalgam root-end filling while the other was associated with extruded root filling material. CONCLUSIONS: By using defined clinical inclusion and exclusion criteria a predictable clinical diagnosis of a persistent periapical lesion due to endodontic origin can be reliably made. Periapical granulomas and cysts were the most common periapical lesions of endodontic origin associated with persistent periapical pathosis with the overall incidence of periapical cysts similar to previous studies. The presence of endodontic material in a high proportion of periapical lesions suggests a cause-effect association with the inference that clinicians should employ canal preparation techniques that limit apical extrusion of material.

Cytokine and chemokine levels in radicular and residual cyst fluids.

BACKGROUND: Cytokines were thought to play an important role for the expansion of odontogenic cysts. The purpose of this study was to evaluate the cytokine and chemokine levels of radicular and residual cyst fluids. METHODS: Cyst fluids were aspirated from 21 patients (11 radicular and 10 residual cysts) and the levels of interleukin-1 alpha (IL-1alpha), tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein-1 (MCP-1), and regulated upon activation normal T cell expressed and secreted (RANTES) were determined by ELISA using commercially available kits. RESULTS: Both radicular and residual cyst fluids contained IL-1alpha, TNF-alpha, MCP-1, and RANTES, concentrations of which were significantly higher in the radicular cyst fluids than those in the residual cysts (P < 0.001 for IL-1alpha, TNF-alpha, and RANTES; P < 0.01 for MCP-1). Compared to the other mediators, the concentration of IL-1alpha was found to be highest in both of the cyst fluids. In addition, positive correlations were found between IL-1alpha, TNF-alpha, MCP-1, and RANTES in radicular and residual cyst fluids. CONCLUSION: If the radicular cyst is inadvertently left behind following tooth extraction, some degree of inflammation may carry on. Residual cysts, although to a lesser extend than radicular cysts, have the potential to expand.

Proliferation of epithelial cell rests, formation of apical cysts, and regression of apical cysts after periapical wound healing.

There is continuing controversy regarding the potential for inflammatory apical cysts to heal after nonsurgical endodontic therapy. Molecular cell biology may provide answers to a series of related questions. How are the epithelial cell rests of Malassez stimulated to proliferate? How are the apical cysts formed? How does the lining epithelium of apical cysts regress after endodontic therapy? Epithelial cell rests are induced to divide and proliferate by inflammatory mediators, proinflammatory cytokines, and growth factors released from host cells during periradicular inflammation. Quiescent epithelial cell rests can behave like restricted-potential stem cells if stimulated to proliferate. Formation of apical cysts is most likely caused by the merging of proliferating epithelial strands from all directions to form a three-dimensional ball mass. After endodontic therapy, epithelial cells in epithelial strands of periapical granulomas and the lining epithelium of apical cysts may stop proliferating because of a reduction in inflammatory mediators, proinflammatory cytokines, and growth factors. Epithelial cells will also regress because of activation of apoptosis or programmed cell death through deprivation of survival factors or by receiving death signals during periapical wound healing.

Complications following replantation of a primary incisor: a cautionary tale.

The replantation of avulsed primary incisors is contra-indicated. This case describes an 8-year-old child who six years previously had avulsed and had replanted a primary central incisor. At presentation, this tooth was retained, the permanent successor had failed to erupt and appearance of the adjacent lateral incisor was notably delayed. Investigation revealed a radicular cyst in relation to the replanted deciduous incisor together with severe displacement of the permanent tooth, which could not be saved.

Radicular cyst arising from a traumatized primary incisor: a case report of a rare complication that emphasizes the need for regular follow up.

Radicular cysts associated with the deciduous dentition are rare. The literature is sparse regarding cysts associated with primary incisor teeth, which is surprising given the frequency with which these teeth are traumatized. Most cases reported involve molar teeth associated with apical infection following on from caries. A case of a 3-year-old boy who developed a large radicular cyst associated with a previously traumatized upper primary incisor is reported.

Association between odontogenic infections and unilateral sinus opacification.

OBJECTIVES: Consideration of the causes of unilateral paranasal sinusitis, which frequently occurs in routine medical care and is often associated with odontogenic infection. STUDY DESIGN: Retrospective data analysis. METHODS: A review of the charts of all 190 patients treated for unilateral paranasal sinusitis at our department between 2005 and 2012 was carried out. All patients were diagnosed based on clinical signs, symptoms, and imaging findings, including computed tomography (CT), orthopantomography (OP), and other modalities. Patients were classified in three groups: patients with odontogenic infection involvement (Group A); patients without odontogenic infection involvement (Group B); and patients with inconclusive odontogenic infection involvement (Group C). RESULTS: The most common cause of unilateral paranasal sinusitis was odontogenic infection, as seen in 138 cases (72.6%), followed by chronic inflammation in 43 cases (22.6%). Among patients diagnosed with odontogenic infection, one patient was also diagnosed with coexistent polyps and mycosis. Based on CT, OP, EPT, and oral examination, final distribution was 138 patients (72.6%) in Group A, 32 (16.8%) in Group B, and 20 (10.5%) in Group C. CONCLUSIONS: Odontogenic infection involvement was implicated in approximately 70% cases of unilateral paranasal sinusitis. Odontogenic maxillary sinusitis can be difficult to diagnose, and consideration of imaging performed under various conditions is recommended. In order to determine the most appropriate treatment for unilateral paranasal sinusitis, whether such treatment will be surgery, dental treatment, conservative therapy, or other treatments, collaboration between concerned doctors is essential.

The structure of bovine periodontal ligament with special reference to the epithelial cell rests.

The aim of this study was to determine the structure of the bovine periodontal ligament, with special reference to epithelial cell rests (ECR) and their cytokeratin content. Periodontal ligament was obtained from bovine molar teeth and studied at both the light microscopic and electron microscopic levels. Cytokeratin content was determined using immunohistochemistry against a number of cytokeratin antibodies and specificity tested against bovine and human oral mucosa. Collagen fibril diameters and the area of a fiber bundle occupied by collagen were determined using a digital planimeter with a digitizing tablet. The majority of periodontal fibroblasts possessed considerable quantities of roughened endoplasmic reticulum, indicating rapid synthesis and secretion of collagen, but no intracellular collagen profiles were present. Endothelial cells showed Weibel-Palade bodies. Collagen fibril diameters showed a unimodal distribution with a mean collagen fibril diameter of 55.3 nm. The mean percentage area of the extracellular matrix occupied by collagen was 42%. Structurally, ECR were unusual in exhibiting large numbers of microvilli and conspicuous amounts of cytokeratin filaments. Bovine ECR showed a positive reaction to the pancytokeratin MNF116 (which reacts with the cytokeratins 5, 6, 8, 17, and probably 19), to PCK-26 (which reacts with the type II cytokeratins 1, 5, 6, and 8) and to cytokeratin 13. There was no reaction for cytokeratins 1, 4, 10, 11 and 18. Structurally, bovine periodontal ligament showed features common to other species. However, ECR in terms of both structure and cytokeratin content showed features indicative of important species differences which may have relevance when considering the etiology of radicular cysts.

Production of human-inducible nitric oxide synthase in radicular cysts.

To examine if nitric oxide (NO) is produced in radicular cysts, NO synthase (NOS) production was analyzed. Periapical tissues were removed from patients at the time of endodontic surgery. Frozen tissue sections were histologically evaluated with hematoxylin-eosin staining. Production of human-inducible NOS (iNOS) in apical cysts was then immunohistochemically examined. Immunoreactive human iNOS was widely distributed in epithelial cells, endothelial cells, fibroblasts, macrophages, or polymorphonuclear leukocytes. Remarkably, iNOS-positive cells were significantly present around blood vessels, and cells residing apart from the blood vessels showed weak or no iNOS production, suggesting that only cells around blood vessels could be stimulated for iNOS synthesis. These data demonstrated the possibility that several, but not all, cells could be stimulated to synthesize iNOS in inflamed tissues. In the presence of iNOS, NO can be produced spontaneously in periapical lesions and may play a crucial role in the regulation of chronic infection.

Incidence of periradicular pathoses in endodontic treatment failures.

Biopsy reports from 150 periradicular tissue specimens obtained from teeth refractory to nonsurgical endodontic therapy were reviewed. The specimens were submitted by postdoctoral dental students in the Department of Endodontics, and the biopsy reports were prepared by oral pathologists at the University of Texas Health Science Center at San Antonio. The study found that 59.3% of the periradicular lesions were granulomas, 22% cysts, 12% scars, and 6.7% other pathoses. The majority (56%) of endodontically treated cases which failed to heal were recognized within 2 yr after the completion of therapy. The most common location for surgical retreatment was the anterior maxilla, followed by the posterior maxilla, the posterior mandible, and the anterior mandible. The periapical granuloma was the predominant pathosis at each location.

The role of endotoxin and cytokines in the pathogenesis of odontogenic cysts.

Odontogenic cysts arise from tooth-forming epithelial residues. The stimulus for the formation of radicular cysts is thought to be endotoxin released from the infected necrotic tooth pulp. However, in keratocysts and follicular cysts, such a stimulus is not present. In order to investigate what drives the cyst epithelium to proliferate, explant media and fluids from 16 radicular cysts, eight keratocysts and seven follicular cysts and explant media from four specimens of non-inflamed gingival tissue were examined for the presence of endotoxin and cytokines. Cyst fluids were also cultured for 72 h in anaerobic and aerobic conditions to detect micro-organisms. Endotoxin from three different bacteria, cytokines [interleukin-(IL) 1 alpha, IL-1 beta and IL-6] as well as prostaglandin E2 (PGE2) were tested in an epithelial cell-proliferation assay. As the cyst epithelium is supported by a connective tissue capsule, the effect of fibroblast culture media on epithelial cell proliferation was also investigated. The results showed significantly higher concentrations of endotoxin in radicular cyst fluid than in the keratocyst or the follicular cyst. None of the cyst fluids contained micro-organisms. Immunoassays demonstrated the presence of IL-1 alpha and -6 in all fluids and explants tested; IL-1 beta was only found in the inflammatory radicular cysts. However, reverse transcriptase-polymerase chain reaction showed that mRNAs for IL-1 alpha, -1 beta and -6 were present in all cyst types. Proliferation studies indicated that endotoxin and the cytokines had a mitogenic effect on epithelia at low concentrations; PGE2 had very little effect at low concentrations, and had an inhibitory effect at high concentrations. Cyst fibroblast culture media had a mitogenic effect on the epithelia that was enhanced by the presence of endotoxin.

Odontogenic cysts related to pulpotomized deciduous molars: clinical features and treatment outcome.

OBJECTIVE: The purpose of this study was to assess the morbidity and outcomes associated with large cysts that developed in conjunction with pulpotomized deciduous molars. STUDY DESIGN: This retrospective study was based on the files of 18 patients who were referred to 2 oral surgery departments during a 10-year period (1986-1996). The inclusion criteria were large cyst lesions (>1 cm in diameter) and complete documentation. Data regarding symptoms at presentation, histologic and radiologic features, treatment modalities, morbidity, and outcomes were analyzed. RESULTS: An equal gender distribution of patients was found, as were a later development in males (12+/-2 years in boys, 9+/-2 years in girls) and a 5:1 ratio favoring the mandible over the maxilla. Treatment included enucleation (12 patients) and marsupialization (6 patients). The morbidity was high and included loss of permanent teeth (3 patients), extensive loss of alveolar bone (3 patients), use of flaps (2 patients), and adjuvant orthodontic treatment (9 patients). CONCLUSION: Failure of early detection and treatment of cysts that develop in conjunction with pulpotomized deciduous molars can cause considerable morbidity. Therefore, periodic clinical and radiologic follow-up until the eruption of succedaneous teeth is recommended.

Horizontal root fracture--an unusual complication.

Cystic change at the site of a root fracture is an unusual sequelae. A case report of such an occurrence in a horizontal root fracture involving the apical third of a permanent central incisor in a 22-year-old man is presented and management of these injuries is discussed in brief.

The periapical space--a dynamic interface.

The ultimate aim of endodontic treatment is to encourage the healing of apical periodontitis, or to prevent it from occurring if it was not present prior to treatment. Apical periodontitis is a general term used to describe an inflammatory response to irritation caused by the contents of a root canal system and it has several distinct forms. The most common is a granuloma but this can develop into other disease entities such as an abscess, a periapical pocket cyst or a true cyst, all of which present as radiolucencies. However, periapical radiolucencies may also be caused by extra-radicular infections, foreign body reactions and periapical scars, or they may be due to other tumours and cysts that have not originated from pulp disease. Practitioners must recognise and understand the different pathological entities and the dynamic interactions that occur in the periapical tissues in order to correctly diagnose and treat these conditions.

Suspension mechanism of subperiosteal implants in baboons.

It has been noted that overloading of an implant can lead to the premature loss of implants (Jones et al., 1979; Travis and Jones, 1986). An understanding of the mechanism by which subperiosteal implants support masticatory loads could lead to appropriate design changes for best utilization of this mechanism and thus increase the predictability of subperiosteal implants (James, 1983). This study attempts to analyze the suspension mechanism in implants recovered from a baboon after 10 years' use.

Development of periapical lesions.

The purpose of the present study was to follow the development of periapical lesions both radiographically and histologically in infected teeth with open and sealed root canals. The mandibular premolars from five adult monkeys were used in the experiment. Sealed infected teeth developed radiographic signs of periapical pathosis significantly earlier than unsealed teeth. Although, histological signs of pathology could be seen periapically at earlier observation periods, sealed teeth consistently developed these changes earlier than unsealed teeth. Furthermore, the histological periapical pathology differed somewhat between the two groups in that unsealed teeth showed a multi-focal diffuse pattern of spreading.