Preferred Reporting Items for Diagnostic Accuracy Studies in Endodontics (PRIDASE) guidelines: a development protocol.

Diagnostic accuracy studies play an important role in informing clinical practice and patient management, by evaluating the ability of diagnostic testing and imaging to identify the presence or absence of a disease or condition. These studies compare the relative diagnostic strength of the test or device with a reference standard, therefore, guiding clinical decisions on the reliability of the test, the need for further tests, and whether to monitor or treat a particular condition. Inadequate and incomplete reporting of diagnostic accuracy studies can disguise methodological deficiencies and ultimately result in study bias and the inability to translate research findings into daily clinical practice. The Preferred Reporting Items for Diagnostic Accuracy Studies in Endodontics (PRIDASE) guidelines are being developed in order to improve the accuracy, transparency, completeness and reproducibility of diagnostic accuracy studies in the speciality of Endodontology. The aim of this paper is to report the process used to develop the PRIDASE guidelines based on a well-established consensus process. The project leaders (PD, VN) formed a steering committee of nine members (PD, VN, PA, AF, DR, SP, CK, MP, HD) to oversee and manage the project. The PRIDASE steering committee will develop the initial draft of the PRIDASE guidelines by adapting and modifying the Standards for Reporting of Diagnostic Accuracy Studies (STARD) 2015 guidelines, adding new items related specifically to the nature of Endodontics and incorporate the Clinical and Laboratory Images in Publication (CLIP) principles. The initial guidelines will consist of a series of domains and individual items and will be validated by the members of a PRIDASE Delphi Group (PDG) consisting of a minimum of 30 individuals who will evaluate independently the individual items based on two parameters: 'clarity' using a dichotomous scoring (yes/no) and 'suitability' for inclusion using a 9-point Likert Scale. The scores awarded by each member and any suggestions for improvement will be shared with the PDG to inform an iterative process that will result in a series of items that are clear and suitable for inclusion in the new PRIDASE guidelines. Once the PDG has completed its work, the steering committee will create a PRIDASE Meeting Group (PMG) of 20 individuals from around the world. Members of the PDG will be eligible to be the part of PMG. The draft guidelines and flowchart approved by the PDG will then be presented for further validation and agreement by the PMG. As a result of these discussions, the PRIDASE guidelines will be finalized and then disseminated to relevant stakeholders through publications and via the Preferred Reporting Items for study Designs in Endodontology (PRIDE) website (http://pride-endodonticguidelines.org). Periodic updates to the PRIDASE guidelines will be made based on feedback from stakeholders and end-users.

Association between diabetes and the outcome of root canal treatment in adults: an umbrella review.

BACKGROUND: Diabetes mellitus is the most common metabolic disorder amongst dental patients. The association between the diabetes and the outcome of root canal treatment is unclear. AIM: To conduct an umbrella review to determine whether there is an association between diabetes and the outcome of root canal treatment. DATA SOURCE: The protocol of the review was developed and registered in the PROSPERO database (CRD42019141684). Four electronic databases (PubMed, EBSCHOhost, Cochrane and Scopus databases) were used to perform a literature search until July 2019. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS: Systematic reviews with or without meta-analyses published in English assessing any outcomes of root canal treatment comparing diabetic and nondiabetic patients were included. Two reviewers were involved independently in study selection, data extraction and appraising the reviews that were included. Disagreements were resolved with the help of a third reviewer. STUDY APPRAISAL AND SYNTHESIS METHODS: The quality of the reviews was assessed using the AMSTAR tool (A measurement tool to assess systematic reviews), with 11 items. Each AMSTAR item was given a score of 1 if the criterion was met, or 0 if the criterion was not met or the information was unclear. RESULTS: Four systematic reviews were included. The AMSTAR score for the reviews ranged from 5 to 7, out of a maximum score of 11, and all the systematic reviews were classified as 'medium' quality. LIMITATIONS: Only two systematic reviews included a meta-analysis. Only systematic reviews published in English were included. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Diabetes mellitus is associated with the outcome of root canal treatment and can be considered as a preoperative prognostic factor.

Preferred Reporting items for OBservational studies in Endodontics (PROBE) guidelines: a development protocol.

Observational studies have a significant role in establishing the prevalence and incidence of diseases in populations, as well as determining the benefits and risks associated with health-related interventions. Observational studies principally encompass cohort, case-control, case series and cross-sectional designs. Inadequate reporting of observational studies is likely to have a negative impact on decision-making in day-to-day clinical practice; however, no reporting guidelines have been published for observational studies in Endodontics. The aim of this project is to develop reporting guidelines for authors when creating manuscripts describing observational studies in the field of Endodontology in an attempt to improve the quality of publications. The new guidelines for observational studies will be named: 'Preferred Reporting items for OBservational studies in Endodontics (PROBE)'. A steering committee was formed by the project leaders (PD, VN) to develop the guidelines through a five-phase consensus process. The steering committee will review and adapt items from the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) statement and the Clinical and Laboratory Images in Publications (CLIP) principles, as well as identify new items that add value to Endodontics. The steering committee will create a PROBE Delphi Group (PDG), consisting of 30 members across the globe to review and refine the draft checklist items and flowchart. The items will be assessed by the PDG on a nine-point Likert scale for relevance and inclusion. The agreed items will then be discussed by a PROBE Face-to-Face meeting group (PFMG) made up of 20 individuals to further refine the guidelines. After receiving feedback from the PFMG, the steering committee will pilot and finalize the guidelines. The approved PROBE guidelines will be disseminated through publication in relevant journals, and be presented at national and international conferences. The PROBE checklist and flowchart will be available and downloadable from the Preferred Reporting Items for study Designs in Endodontics (PRIDE) website: www.pride-endodonticguidelines.org. The PROBE steering committee encourages clinicians, researchers, editors and peer reviewers to provide feedback on the PROBE guidelines to inform the steering group when the guidelines are updated.

Effectiveness of full Pulpotomy compared with Root canal treatment in managing teeth with signs and symptOms indicative of irreversible pulpitis: a protocol for prospectiVE meta-analysis of individual participant data of linked randomised clinical trials (PROVE).

BACKGROUND: Full pulpotomy has been proposed as an alternative to root canal treatment in teeth with signs and symptoms indicative of irreversible pulpitis (IRP), but the evidence is limited, relying on underpowered studies with a high risk of bias. The aim of this study is to conduct a prospective meta-analysis (PMA) of individual participant data of a series of individual randomised trials to provide robust evidence on the clinical and cost-effectiveness of pulpotomy compared with root canal treatment. METHODS: Individual participant data will be obtained from a series of randomised trials designed and conducted by a consortium of multi-national investigators with an interest in vital pulp treatment. These individualised trials will be conducted using a specified protocol, defined outcomes, and outcome measures. Ten parallel-group randomised trials currently being conducted in 10 countries will provide data from more than 500 participants. The primary outcome is a composite measure defined as (1) the absence of pain indicative of IRP, (2) the absence of signs and symptoms indicative of acute or chronic apical periodontitis, and (3) the absence of radiographic evidence of failure including radiolucency or resorption. Individual participant data will be obtained, assessed, and checked for quality by two independent reviewers prior to the PMA. Pooled estimates on treatment effects will be generated using a 2-stage meta-analysis approach. The first stage involves a standard regression analysis in each trial to produce aggregate data on treatment effect estimates followed by an inverse variance weighted meta-analysis to combine these aggregate data and produce summary statistics and forest plots. Cost-effectiveness analysis based on the composite outcome will be undertaken as a process evaluation to evaluate treatment fidelity and acceptability by patients and dentists. RESULTS: The research question and trial protocol were developed and approved by investigators in all 10 sites. All sites use shared resources including study protocols, data collection forms, participant information leaflets, and consent forms in order to improve flow, consistency, and reproducibility. Each site obtained its own Institutional Review Board approval, and trials were registered in appropriate open access platforms. Patient recruitment has started in most sites, as of July 2023. DISCUSSION: PMA offers a rigorous, flexible, and efficient methodology to answer this important research question and provide results with improved generalisability and external validity compared with traditional trials and retrospective meta-analyses. The results of this study will have implications for both the delivery of clinical practice and structured clinical guidelines' development. TRIAL REGISTRATION: PROSPERO CRD42023446809. Registered on 08 February 2023.

The microbial challenge to pulp regeneration.

Pulp regeneration is considered in cases where the dental pulp has been destroyed because of microbial irritation. Diverse oral and food-borne micro-organisms are able to invade the pulp space, form biofilm on canal walls, and infiltrate dentinal tubules. Prior to pulp regeneration procedures, the pulp space and dentinal walls need to be sufficiently disinfected to allow for and promote regeneration. The necessary level of disinfection is likely higher than that accepted for traditional endodontic therapy, because in traditional techniques the mere lowering of bacterial loads and prevention of bacterial access to periapical tissues is conducive to healing. Moreover, several of the non-specific antimicrobials used in traditional endodontic therapy may cause significant changes in remaining dentin that interfere with its inherent potential to mediate regeneration. Non-specific antimicrobials also suppress all microbial taxa, which may allow residual virulent micro-organisms to preferentially repopulate the pulp space. Therefore, it is important for endodontic pathogens to be studied by molecular methods that allow for a broad depth of coverage. It is then essential to determine the most effective protocols to disinfect the pulp space, with minimal disruption of remaining dentin. These protocols include the topical use of effective antibiotics, including newer agents that have demonstrated efficacy against endodontic pathogens.

Vertical fracture of root filled teeth restored with posts: the effects of patient age and dentine thickness.

AIM: To determine whether patient age contributed to the fracture resistance of teeth subjected to root canal treatment and post placement. METHODOLOGY: Forty-five single-rooted, single-canal human teeth were mounted, instrumented, obturated and prepared for a post. The teeth were divided into young (18 < or = age < or = 35) and old (60 < or = age) groups and subjected to cyclic loading until fracture; those reaching 200,000 cycles without undergoing failure were then subjected to static loading to fracture. Statistical differences between groups were examined using one-way anovas, and correlations were identified using Pearson's r; significance was established at P < or = 0.05. RESULTS: There was no significant difference between the two age groups in terms of the number of cycles to fracture (P > 0.05) or the load to fracture (P > 0.05). However, there was a significant correlation (P < or = 0.05) between the root fracture resistance and individual age, indicating that the susceptibility to root fracture increases significantly with increasing patient age. Also, the dentine thickness of roots that fractured was significantly less than those that did not (P = 0.04). CONCLUSION: Vertical root fracture of teeth receiving root canal treatment with posts is more likely to occur in the teeth of older patients (60+) and particularly in those with low dentine thickness.

Proteomic analysis of endodontic infections by liquid chromatography-tandem mass spectrometry.

INTRODUCTION: Endodontic infections are very prevalent and have a polymicrobial etiology characterized by complex interrelationships between endodontic microorganisms and the host defenses. Proteomic analysis of endodontic infections can provide global insights into the invasion, pathogenicity mechanisms, and multifactorial interactions existing between root canal bacteria and the host in the initiation and progression of apical periodontitis. The purpose of this study was to apply proteomic techniques such as liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the identification of proteins of bacterial origin present in endodontic infections. METHODS: Endodontic specimens were aseptically obtained from seven patients with root canal infections. Protein mixtures were subjected to tryptic in-solution digestion and analysed by reverse-phase nano-LC-MS/MS followed by a database search. RESULTS: Proteins, mainly of cell wall or membrane origin, from endodontic bacteria especially Enterococcus faecalis, Enterococcus faecium, Porphyromonas gingivalis, Fusobacterium nucleatum, and Treponema denticola were identified from all the samples tested. Identified proteins included adhesins, autolysins, proteases, virulence factors, and antibiotic-resistance proteins. CONCLUSIONS: LC-MS/MS offers a sensitive analytical platform to study the disease processes in the root canal environment. The array of proteins expressed in endodontic infections reflects the complex microbial presence and highlights the bacterial species involved in the inflammatory process.

Effect of Residual Bacteria on the Outcome of Pulp Regeneration In Vivo.

It is not known to what extent residual infection may interfere with the success of pulp regeneration procedures. The aim of this study was to determine, radiographically and histologically, the effect of residual bacteria on the outcome of pulp regeneration mediated by a tissue-engineered construct as compared with traditional revascularization. Periapical lesions were induced in 24 canine teeth of 6 ferrets. After disinfection with 1.25% NaOCl and triple antibiotic paste, ferret dental pulp stem cells, encapsulated in a hydrogel scaffold, were injected into half the experimental teeth. The other half were treated with the traditional revascularization protocol with a blood clot scaffold. After 3 mo, block sections of the canine teeth were imaged radiographically and processed for histologic and histobacteriologic analyses. Associations between variables of interest were evaluated through mixed effects regression models. There were no significant differences between the 2 experimental groups in radiographic root development ( P > 0.05). There was a significant association between the presence of persistent periapical radiolucency and root wall thickness ( P = 0.02). There was also no significant difference in histologic findings between the 2 experimental groups ( P > 0.05). The presence of residual bacteria was significantly associated with lack of radiographic growth ( P < 0.001). The amount of dentin-associated mineralized tissue formed in teeth with residual bacteria was significantly less than in teeth with no residual bacteria ( P < 0.001). Residual bacteria have a critical negative effect on the outcome of regenerative endodontic procedures.

IL-1 alpha and TNF-alpha expression in early periapical lesions of normal and immunodeficient mice.

T-helper and B-lymphocytes may contribute to mechanisms that result in bone-resorptive cytokine production in periapical lesion. Mice with severe combined immunodeficiency (scid) lack functional B- and T-cell immunity. The purpose of this study was to investigate the progression of pulp necrosis and the histomorphometric features of periapical lesions in scid vs. normal mice. The expression of the bone-resorptive cytokines IL-1 alpha and TNF-alpha was also investigated. Sixteen five-week-old homozygous scid mice and 14 normal BALB/cJ mice were used. The pulps of mandibular first molars were exposed for 1, 2, 3, or 4 weeks. Blocks of tissue containing the mandibular teeth and supporting structures were processed for both light microscopic examination and immunohistochemical staining for IL-1 alpha dna TNF-alpha. Central sections were randomized, their images were blindly digitized into a computer, and the areas of the lesions surrounding the distal root apices were measured. The cells that stained positively for the cytokines in the same area of adjacent sections were counted. Pulp necrosis progressed at similar rates in teeth from both strains. A progressive and significant increase in the periapical lesion size in both strains was observed. The scid mice lesions were significantly smaller than the controls at only the three-week period. There was heavy cytokine staining in periapical lesions from both strains, especially in areas that contained a mixed inflammatory infiltrate or fibroblasts. The number of positively staining cells was proportional to the lesion size. Therefore, pulpal and periapical pathosis were independent of the presence of functional T- and B-cells in this model.

Effect of using electronic apex locators on selected endodontic treatment parameters.

The purpose of this study was to determine the effect of using electronic apex locators on the number of radiographs taken and the adequacy in length of the final obturation. Patients in an undergraduate student endodontics clinic participated in the study. The working length (WL) was estimated by the authors for all cases (36 teeth; 58 canals), using both a preoperative standardized radiograph and an electronic measurement. The students were then asked to place WL files to one of the estimates (electronic or radiographic; chosen by random assignment) and take a WL radiograph. Neither the students nor their instructors knew which method was chosen for the estimates. Once treatment was completed, the total number of working radiographs was counted. The number of cases with acceptable (0 to 2 mm short of the apex) or unacceptable obturation was also blindly registered. An electronic estimate of the WL improved length quality of the final obturation, compared with a radiographic estimate. The number of working radiographs taken was less in the electronic apex locator group in anterior and premolar teeth, but not in molars.

An in vitro comparison of five root canal length measuring instruments.

Several new root canal length measuring instruments (RCLMI) have recently been introduced claiming superiority over older systems. The purpose of this study was to compare five models of these instruments with respect to their accuracy under a given set of specified conditions. The five RCLMI tested were: the, Exact-a-pex, the Endocater, the Neosono-D, the Apex Finder, and the Sono-Explorer, Mark III. The conditions tested were the accuracy of the instruments in determining the working length, the consistency of measurement following canal instrumentation and with conductive gutta-percha points in place, and the operation of the RCLMI in the presence of fluids frequently found in root canals during endodontic treatment. An in vitro model was used to test these instruments. A set of 20 teeth was tested using the conditions specified above. All data were compared using the mean difference from the actual canal length of the teeth. The results indicated that there were no significant differences among measurements derived from the five instruments, under the specified conditions. There was a slight variation of the measurements by all instruments when they were used following instrumentation and with the use of conductive gutta-percha points. When fluids were present in the canals, the reliability of the RCLMI depended on the electrical conductivity of the fluid tested. The poorest results were obtained when either sodium hypochlorite or blood were present in the canals.

Accuracy of the Endex with variations in canal irrigants and foramen size.

Several electronic apex locators (EALs) are currently available. The manufacturer of a new device, the Endex, claims that it is accurate regardless of canal conditions. This study compared the accuracy of the Endex with that of the Exact-a-pex, the Sono-Explorer Mark III, and the Neosono-D SE as to the effects of fluids in the canal and variation in foramen size. Sixty extracted single-canaled teeth were divided into two groups (narrow and wide foramina), depending on whether the apical foramina permitted the tip of a #30 K file to pass through. An in vitro model was used, in which teeth were fitted in test tubes with the roots immersed in 1% agar in phosphate-buffered saline. Root canal lengths were measured in dry canals, then with ethanol, Xylocaine, and sodium hypochlorite in the canals by each electronic apex locator. These lengths were compared with those of the actual root canal lengths. No significant differences were noted among the instruments in dry canals regardless of the foramen size. The endex was generally superior to the other instruments examined in canals containing conductive fluids, especially where the apical foramen was widened.

Healing of induced periapical lesions in ferret canines.

A previous study showed that the ferret canine is an appropriate model for inducing periapical lesions. Ferret canines were used in this study to study changes in periapical lesions after root canal treatment (RCT). After periapical pathosis was induced in the maxillary and mandibular canines of six ferrets, RCT was performed on three of the four canines in each animal. Each ferret received periodic intraperitoneal injections of Procion red dye. Two animals were killed at each of 4, 8, and 12 wk after RCT. Apices and surrounding lesions were evaluated radiographically, histologically, and by fluorescent microscopy. Periapical radiolucencies increased in size during induction but showed no changes after RCT. Lesions in untreated teeth showed features of granulomatous inflammation, mainly the presence of macrophages and lymphocytes. After RCT, there was histological evidence of healing in the form of cementum deposition, increased vascularity, and increased fibroblastic and osteoblastic activity. Fluorescent staining showed cementum deposition of variable thickness in the treated specimens.

Clinical evaluation of five electronic root canal length measuring instruments.

A previous in vitro study has shown high accuracy, but no clinically significant differences in a group of five electronic root canal length measuring instruments. The purpose of this study was to evaluate and compare the performance of the same group of instruments under clinical conditions and to correlate their accuracy to radiographic estimates of canal length. Five electronic root canal length measuring instruments were used to measure the working length to the "apex" in 20 single-rooted teeth scheduled for extraction. After extraction, the actual canal length was measured visually to a point just within the apical foramen. This length was compared with instrument length as determined electronically. The accuracy of the instruments in determining canal measurement within +/- 0.5 mm from the apical foramen varied from 55 to 75%. The differences between the instruments were not statistically significant. On average, all of the instruments except for the Endocater gave canal length measurements that were beyond the apical foramen. The variability of the measurements, which was comparable to that of estimates of canal length from preoperative radiographs, indicated that radiographic verification of the working length is still desirable.

Penicillin as a supplement in resolving the localized acute apical abscess.

PROBLEM: Antibiotics are often prescribed indiscriminately to treat endodontic emergencies. OBJECTIVES: This study examined (1) the effect of penicillin supplementation on reduction of symptoms and (2) the course of recovery of localized acute apical abscess after emergency treatment. STUDY DESIGN: Patients with pulp necrosis and periapical pain and/or localized swelling were considered. Those eligible did not have any signs of spreading infections. Patients received appropriate local treatment, and a double-blind protocol was used to randomly assign them to one of three groups: penicillin VK group, placebo group, or neither medication group. All received ibuprofen 600 mg four times daily for 24 hours. Patients entered their pre- and postoperative pain and swelling experience on a visual analog scale for up to 72 hours. RESULTS: Resolution was fairly rapid in most patients. Statistical analysis of the scores of 32 respondents revealed no significant differences (at p < 0.05) between the three groups in course of recovery or symptoms at any time period. CONCLUSIONS: Patients with localized periapical pain or swelling generally recovered quickly with local treatment. The data did not show a demonstrable benefit from penicillin supplementation.

Effects of enamel matrix derivative on gene expression of primary osteoblasts.

OBJECTIVE: The aim of this study was to investigate the effects of enamel matrix derivative (EMD) on gene expression of collagen alpha1 (I), osteocalcin, prostaglandin G/H synthase 2 (PGHS-2), interleukin-6, and insulin-like growth factor I in primary mouse osteoblasts. STUDY DESIGN: Primary osteoblasts were digested from 6- to 8-day-old mouse calvaria. Cells were divided into 4 groups and cultured for 24, 48, and 72 hours with a serum-free modified Eagle medium as negative control, modified Eagle medium with 25 microg/mL EMD, modified Eagle medium with 100 microg/mL EMD, and modified Eagle medium plus 10% fetal bovine serum as positive control. Gene expression was determined by Northern blot and reverse transcription polymerase chain reaction analysis. RESULT: EMD enhanced collagen I, interleukin-6, and PGHS-2 expression and did not stimulate the expression of osteocalcin and IGF-I. CONCLUSION: These results indicate that EMD might regulate certain gene expression during periodontal tissue regeneration.

Effectiveness of an endodontic diagnosis computer simulation program.

The effectiveness of a recently developed endodontic diagnosis computer simulation program was examined. Third-year dental students (n = 90) in three successive academic classes were given a pre-test in endodontic diagnosis before any endodontic instruction, and then received ten lectures on diagnostic techniques, endodontic pathology, and radiographic interpretation. The students were subsequently divided into three equal groups not differing statistically on their pre-test results. The first group used an endodontic computer simulation program containing fifteen patient simulations for one hour. The second group had a small-group seminar aiming to cover the same material as in the computer program in the same time period. The third group (control) had no further instruction. The three groups then took a post-test to evaluate their diagnostic knowledge in endodontics. The improvement of scores from pre- to post-test in the three groups were statistically different (p = 0.018). The simulation group students improved significantly more than the seminar group (p = 0.05) and the Control Group (p = 0.0024). Difference in improvement between the seminar group and the control group was not statistically significant (p = 0.20). Students were able to cover more cases on average using the simulation program than were covered in the seminar (t-test, p < 0.0001).

Analyzing endodontic infections by deep coverage pyrosequencing.

Bacterial diversity in endodontic infections has not been sufficiently studied. The use of modern pyrosequencing technology should allow for more comprehensive analysis than traditional Sanger sequencing. This study investigated bacterial diversity in endodontic infections through taxonomic classification based on 16S rRNA gene sequences generated by 454 GS-FLX pyrosequencing and conventional Sanger capillary sequencing technologies. Sequencings were performed on 7 specimens from endodontic infections. On average, 47 vs. 28,590 sequences were obtained per sample for Sanger sequencing vs. pyrosequencing, representing a 600-fold difference in "depth-of-coverage". Based on Ribosomal Database Project (RDP II) Classifier analysis, pyrosequencing identified 179 bacterial genera in 13 phyla, which was significantly more than Sanger sequencing. The phylum Bacteroidetes was the most prevalent bacterial phylum. These results indicate that bacterial communities in endodontic infections are more diverse than previously demonstrated. In addition, deep-coverage pyrosequencing of the 16S rRNA gene revealed low-abundance micro-organisms with potential clinical implications.

Periapical lesion progression and cytokine expression in an LPS hyporesponsive model.

AIM: The purpose of this study was to compare periapical lesion progression and the expression of the bone modulating cytokines IL-1alpha, TNF-alpha, IL-4, IL-6 and IL-11 in periapical lesions of normal and C3H/HeJ (LPS hyporesponsive) mice. METHODOLOGY: Pulps of both mandibular first molars from C3H/HeJ and BALB/c (normal) mice were exposed and inoculated with normal mouse oral microorganisms for 2, 4, 6, and 8 weeks. After euthanasia, specimens were prepared for histological examination. A quantitative evaluation of the lesional area and immunohistochemical stain counts was performed. RESULTS: There were no statistically significant differences in progression of periapical lesions for both mouse strains with time (two-factor ANOVA, P > 0.05). The immunohistochemical staining revealed no overall differences between the two strains in levels of expression of the cytokines (P > 0.05). IL-11 expression did not change from control levels in BALB/c mice, but correlated with the expression of IL-6 and IL-4 in C3H/HeJ mice. CONCLUSION: Responsiveness to LPS may not be significant in the pathogenesis of periapical lesions and in cytokine expression within the lesions, when the lesions are induced by non-specific oral flora.