Etiología, fisiopatología y tratamiento de la periodontitis apical. Revisión de la literatura / Etiology, pathophysiology and treatment of apical periodontitis. Literature review

La periodontitis apical (PA) es una inflamación y destrucción de los tejidos periapicales comúnmente causada por bacterias como resultado de caries o traumatismos dentales. Aunque los mecanismos de defensa del huésped están activados, la acción bacteriana provoca la destrucción apical. Se ha identificado la microbiota relacionada con esta patología en el interior del conducto radicular. Enterococcus faecalis es un coco grampositivo presente en casos clínicos persistentes de PA. Un tratamiento de conducto puede eliminar los agentes infecciosos. Sin embargo, si la PA persiste, se puede considerar un retratamiento del conducto radicular o una apicectomía. Aunque el diagnóstico definitivo de PA se logra mediante un examen histopatológico, los estudios de investigación confirman que es más probable que la tomografía computarizada de haz cónico detecte PA que la radiografía periapical (RP). El objetivo de esta revisión de la literatura es describir la etiología, índice periapical, clasificación de la periodontitis apical: aguda y crónica, así como pruebas diagnósticas adicionales y alternativas de tratamiento para su abordaje clínico. (AU)

Apical Periodontitis (AP) is an inflammation and destruction of the periapical tissues commonly caused by bacteria as a result of dental caries or trauma. Although the host's defense mechanisms are activated, the bacterial action causes apical destruction. The microbiota related to this pathology has been identified inside the root canal of teeth. Enterococcus faecalis is a gram-positive cocci present in persistent clinical cases of AP. A root canal treatment can eliminate the infectious agents. However, if AP persists, a root canal retreatment or an apicoectomy can be considered. Although the definitive diagnosis of AP is achieved by histopathological examination, research studies confirm that cone beam computed tomography is more likely to detect AP than periapical radiography (RP). The objective of this literature review is to describe the etiology, periapical index, apical periodontitis classification: acute and chronic, as well as additional diagnostic test and treatment alternatives for its clinical approach. (AU)

Effects of 5-lipoxygenase gene disruption on inflammation, osteoclastogenesis and bone resorption in polymicrobial apical periodontitis.

OBJECTIVES: To investigate the regulation of inflammatory and osteoclastogenic signaling by 5-lipoxygenase (5-LO) in apical periodontitis induced by oral contamination of dental root canals in mice. DESIGN: Apical periodontitis was induced in 5-lipoxygenase enzyme knockout (129-Alox5tm1Fun) and 129 wild-type mice (n = 96) by exposure of the dental root canal to the oral cavity. After 7, 14, 21, and 28 days, the animals were euthanized and the tissues removed (n = 12 teeth per period) for histopathological and histometric analyses (hematoxylin and eosin [HE]), evaluation of osteoclastogenic activity (tartrate-resistant acid phosphatase enzyme [TRAP]), and determination of inflammatory and osteoclastogenic signaling (qRT-PCR). RESULTS: Oral contamination of dental root canals induced recruitment of neutrophils and osteoclasts to the periodontal ligament, resulting in bone resorption. Absence of 5-LO did not impair neutrophil recruitment while osteoclastic formation was increased. Nonetheless, early bone resorption progressed similarly to lesions in wild-type animals. Interestingly, in the absence of 5-LO, the synthesis of mRNAs for cytokines, chemokines, and their receptors was significantly reduced while that of regulators of osteoclastogenesis (RANK, RANKL, and OPG) was increased in comparison with the corresponding levels in wild-type animals. CONCLUSIONS: The 5-LO pathway plays a role in the stimulation of inflammatory mediator synthesis and inhibition of osteoclastogenesis in apical periodontitis in mice. However, the paradoxical inflammatory-osteoclastogenic signaling did not impair inflammatory cell recruitment and bone resorption during early development of the disease.

The influence of adrenergic blockade in rats with apical periodontitis under chronic stress conditions.

OBJECTIVE: To investigate the influence of chronic stress and adrenergic blockade in a rat model of apical periodontitis. METHODS: Thirty-two Wistar rats were submitted to an animal model of periapical lesion and randomly divided into 4 groups (n = 8): no stress (NS); stress + saline solution (SS); stress + ß-adrenergic blocker (Sß); stress + α-adrenergic blocker (Sα). The SS, Sß and Sα groups were submitted to an animal model of chronic stress for 28 days and received daily injections of saline solution, propranolol (ß adrenergic blocker) and phentolamine (α adrenergic blocker), respectively. After 28 days the animals were euthanized and the following analyses were carried out: a) serum corticosterone levels through Radioimmunoassay; b) measurement of serum levels of IL-1B, IL-6, IL-10 and IL-17 by enzyme-linked immunosorbent assay (ELISA); c) volume of periapical bone resorption by micro-computed tomography; d) histomorphometric analysis by staining with hematoxylin and eosin; e) expression of ß-AR, α-AR, receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) by immunohistochemistry; f) tartrate-resistant acid phosphatase (TRAP) staining; g) ex-vivo cytokine release followed by the stimulation with LPS in superfusion system, by ELISA. RESULTS: SS group displayed significantly higher corticosterone levels than NS group (non-stressed). Higher IL-1ß serum level was observed in the NS group (p < .05); compared to all stressed groups. Other cytokines were present in similar amounts in the serum of all groups. All groups presented similar periapical lesions. All groups presented moderate inflammatory infiltrate, without statistically significant differences between them. No differences were observed regarding ß-AR, α-AR, Rank-L and OPG expression. The number of TRAP-positive cells was significantly decreased in the groups that received daily injections of adrenergic blockers. The IL-1ß release followed LPS stimulation was significantly suppressed when the superfusion media contained propranolol (p < .05). Perfusion containing phentolamine induced a greater release of IL-10. TGF-ß was significantly suppressed by phentolamine perfusion in the NS group (p < .05). CONCLUSIONS: Chronic stress can significantly change the inflammatory cytokines release. Rank-L/OPG system and periapical lesion volume were not affected following the current method applied. The administration of adrenergic blockers was not able to modulate the inflammatory response but presented effectivity in reducing the number of osteoclasts in the periapical region.

JAK2-STAT3 signaling pathway is involved in rat periapical lesions induced by Enterococcus faecalis.

OBJECTIVES: This study aimed to investigate the role of JAK2-STAT3 (Janus kinase 2/signal transducer and activator of transcription 3) in periapical disease caused by Enterococcus faecalis, as well as the correlation between lipoteichoic acid (LTA) in E. faecalis and the activity of the JAK2-STAT3 signaling pathway and osteoclast formation. MATERIALS AND METHODS: A rat model of periapical periodontitis induced by E. faecalis was established. Periapical bone resorption was confirmed by HE staining. The expression of JAK2, p-JAK2, STAT3, and p-STAT3 was assessed with immunohistochemical staining. Osteoclasts were observed through enzyme histochemical staining. LTA acted on mouse osteoclast precursor cells (RAW264.7 cells); a JAK2 inhibitor (AG490) was used to inhibit the JAK2-STAT3 pathway in RAW264.7 cells. The expression of proteins in the JAK2-STAT3 pathway and TRAP (tartrate resistant acid phosphatase) in RAW264.7 cells was also detected. RESULTS: Rat periapical periodontitis was successfully established and bone resorption peaked at day 21. The expression of critical components in the JAK2-STAT3 pathway increased with the progression of inflammation. LTA promoted the differentiation of RAW264.7 cells into osteoclasts. NFATc1 was highly expressed and was inhibited by AG490. CONCLUSIONS: JAK2-STAT3 signaling pathway plays an important role in the process of periapical bone resorption and osteoclastogenesis.

Endothelial Dysfunction Marker Variation in Young Adults with Chronic Apical Periodontitis before and after Endodontic Treatment.

INTRODUCTION: Cardiovascular diseases are the leading cause of mortality worldwide. Apical periodontitis (AP) has been associated with an increased risk of cardiovascular diseases. A correlation has been shown between chronic AP and endothelial dysfunction (ED), but there is no evidence to indicate ED improves after endodontic treatment in patients with periapical lesions. The aim of this study was to investigate vascular and molecular markers of early ED before and after root canal treatment in young adults with chronic AP. METHODS: Twenty control subjects and 21 patients with AP were assessed at baseline. The AP patients were also evaluated 2 and 12 months post-treatment. Endothelial flow reserve was assessed via an endothelial function test, and enzyme-linked immunosorbent assays were used to evaluate plasma levels of proinflammatory cytokines interleukin (IL)-1, IL-6, and tumor necrosis factor alpha; vasoconstrictor ED marker endothelin (ET)-1; circulating endothelial adhesion markers intercellular adhesion molecule 1 (ICAM-1)/CD54 and soluble vascular cellular adhesion molecule (sVCAM)-1/CD106; soluble CD14; and the endothelial leukocyte adhesion molecule (E-selectin). RESULTS: AP was associated with increased serum levels of ET-1, ICAM-1, E-selectin, IL-1, and sCD14, suggesting early vascular ED, with no macroscopic evidence of a reduction in endothelial flow reserve. Root canal treatment ameliorated inflammation and early ED, lowering plasma levels of IL-1, sCD14, ET-1, ICAM-1/CD54, and E-selectin to those of control subjects. CONCLUSIONS: Our findings suggest that AP may drive early vascular ED and that the endodontic therapy of AP ameliorates early ED.

Notch Signaling Pathway in Apical Periodontitis: Correlation with Bone Resorption Regulators and Proinflammatory Cytokines.

INTRODUCTION: The exact mechanisms of periapical bone resorption have not been fully elucidated. This study aimed to analyze the expression of Notch signaling molecules (Notch2, Jagged1, and Hey1) and proinflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin [IL]-1ß, and IL-6) in human apical periodontitis lesions with different receptor activator of nuclear factor kappa B ligand (RANKL)/osteoprotegerin (OPG) ratios and determine their potential correlation. METHODS: The study group consisted of 50 periapical lesions collected in conjunction with apicoectomy. The relative gene expression of the investigated molecules (Notch2, Jagged1, Hey1, RANKL, OPG, TNF-α, IL-1ß, and IL-6) in all tissue samples was analyzed using reverse transcriptase real-time polymerase chain reaction. The Student t test, Mann-Whitney U test, and Spearman correlation were used for statistical analysis. RESULTS: Based on the RANKL/OPG ratio, periapical lesions were either RANKL predominant (RANKL > OPG, n = 33) or OPG predominant (RANKL < OPG, n = 17). Symptomatic lesions occurred more frequently in RANKL-predominant compared with OPG-predominant lesions (24 vs 7, P = .029). Notch2, Jagged1, Hey1, and TNF-α were significantly overexpressed in lesions with predominant RANKL compared with lesions with predominant OPG (P = .001, P = .001, P = .027, and P = .016, respectively). Significant correlations were observed between the investigated genes in periapical lesions. CONCLUSIONS: Notch signaling appeared to be activated in periapical inflammation. An increase in Notch2, Jagged1, Hey1, and TNF-α expression in RANKL-predominant periapical lesions corroborates their joined involvement in extensive periapical bone resorption.

Ultrasonic Irrigant Activation during Root Canal Treatment: A Systematic Review.

INTRODUCTION: The aim of this study was to systematically review the evidence on the cleaning and disinfection of root canals and the healing of apical periodontitis when ultrasonic irrigant activation is applied during primary root canal treatment of mature permanent teeth compared with syringe irrigation. METHODS: An electronic search was conducted of the Cochrane Library, Embase, LILACS, PubMed, SciELO, and Scopus databases using both free-text key words and controlled vocabulary. Additional studies were sought through hand searching of endodontic journals and textbooks. The retrieved studies were screened by 2 reviewers according to predefined criteria. The included studies were critically appraised, and the extracted data were arranged in tables. RESULTS: The electronic and hand search retrieved 1966 titles. Three clinical studies and 45 in vitro studies were included in this review. Ultrasonic activation did not improve the healing rate of apical periodontitis compared with syringe irrigation after primary root canal treatment of teeth with a single root canal. Conflicting results were reported by the in vitro microbiological studies. Ultrasonic activation was more effective than syringe irrigation in the removal of pulp tissue remnants and hard tissue debris based on both clinical and in vitro studies. Ultrasonic activation groups were possibly favored in 13 studies, whereas syringe irrigation groups may have been favored in 3 studies. CONCLUSIONS: The level of the available evidence was low, so no strong clinical recommendations could be formulated. Future studies should focus on the antimicrobial effect and healing of apical periodontitis in teeth with multiple root canals.

Conditioned fear stress increases bone resorption in apical periodontitislesions in Wistar male rats.

OBJECTIVE: Because the impact of conditioned fear stress on apical bone resorption is unknown, the aim of the current studywas to use a rat model to evaluate the impact of conditioned fear stress on the bone resorption of inflammatory apical periodontitis lesions. METHODS: Twenty-five animals were divided into two groups. They underwent a surgical procedure in the first left lower molar tooth to expose the dental pulp and induce inflammatory apical periodontitis lesions through the retention of contamination (bacterial infection) during a 56-day period. The animals in the case group were stressed daily by using electrical stimuli (1.10 mA), whereas the animals in the control group were absent from the stressful stimuli (shocks). The open field test was performed to validate the stress methodology. The jaws were removed and collected for histological and radiographic analyses. RESULTS: Stressed animals presented increased levels of bone loss and inflammatory cells in the root apex in comparison with the control group (P = 0.0001). However, no radiographic differences were observed between the groups (P > 0.05). CONCLUSIONS: Our results demonstrated that conditioned fear stress could modify a periapical lesion by increasing the size of bone loss there. Conditioned fear stress also increased the total number of inflammatory cells compared with the control group. Studies evaluating the impact of conditioned fear stress on human periapical inflammatory lesions should be encouraged.

Comprehensive Characterization of 2 Immature Teeth Treated with Regenerative Endodontic Procedures.

INTRODUCTION: Regeneration of the pulp-dentin complex is the penultimate goal of regenerative endodontic procedures (REPs). Histological outcomes have demonstrated reparative tissue formation in human teeth extracted post-REPs. However, lack of accurate characterization has precluded identification of the true nature of tissues formed post-REP. METHODS: Here, we present 2 case reports of tooth #29 and #9 treated with REPs and demonstrate their clinical, radiographic, and histological outcomes. RESULTS: Clinical outcomes revealed healing of apical periodontitis in both teeth and re-establishment of vitality responses in tooth #29. Moreover, radiographic assessments using 2D and 3D-volumetric analyses demonstrate considerable increase in root development for both teeth. Further, histological outcomes evaluated using Hematoxylin and Eosin and immunohistochemical staining demonstrates presence of vascular and lymphatic structures as well as immune cell markers indicative of regeneration of an immunocompetent pulp. Lastly, examination of hard tissue deposition shows dentin-like tissue in parts of tooth #29 demonstrating for the first time, regeneration of a pulp-dentin complex post-REP. CONCLUSIONS: Collectively, this is the first study demonstrating recapitulation of several tissues commonly found as part of a pulp-dentin complex in teeth treated with REPs.

Healing of Apical Periodontitis in Patients with Inflammatory Bowel Diseases and under Anti-tumor Necrosis Factor Alpha Therapy.

INTRODUCTION: We evaluated healing after nonsurgical primary/secondary endodontic treatment of apical periodontitis (AP) in patients with inflammatory bowel diseases (IBDs) treated with anti-tumor necrosis factor alpha biologic medications (BMs). METHODS: Nineteen patients with 22 teeth affected by AP from the gastroenterology unit of the hospital with IBDs under treatment with BMs formed the study group (the IBD group). Fourteen patients with 22 teeth with AP, matched by age and sex, without systemic diseases and not taking medications formed the control group. Teeth underwent primary or secondary root canal treatments and clinical and radiographic follow-up every 3 months for 24 months. The periapical index score was recorded, and 2 trained and calibrated endodontists evaluated and compared radiographs (weighted kappa values, κ = 0.8). The Mann-Whitney, t, chi-square, Fisher, and Bruner-Langer tests and analysis of variance-type statistics were used as appropriate. RESULTS: The recall rate was 100%. All teeth in the IBD patients and 81% in the control patients healed (P = .108). Initial healing was appreciable at 3 months in the IBD group and 6 months in the control group (P = .174). Overall healing was reached at 6 and 10.5 months in the IBD and control groups, respectively (P = .106). At any time of the experiment, teeth in the IBD patients showed a higher probability of healing (P < .05). Both groups exhibited a similar decrement of the periapical index (P = .291), more significant for the IBD at the 3-month follow-up (P < .05). The 2 BMs used showed a similar trend of healing (P = .628). CONCLUSIONS: The treatment of AP in patients taking BMs had no complications; furthermore, it was associated with faster healing than the controls. These results support the possible therapeutic aid of BMs in treating AP.

Endodontic medicine: interrelationships among apical periodontitis, systemic disorders, and tissue responses of dental materials.

Endodontic medicine, which addresses the bidirectional relationship between endodontic infections and systemic diseases, has gained prominence in the field of endodontics. There is much evidence showing that while systemic disease may influence the pathogenesis of endodontic infection, endodontic infection can also cause systemic alterations. These alterations include more severe bone resorption and inflammation in the periapical area as well as enhanced systemic disease symptoms. Similarly, many reports have described the impact of systemic diseases on the tissue responses to dental materials. Conversely, the local use of dental materials may show systemic effects in the form of altered production of biomarkers. Thus, studies to better understand the mechanisms related to those connections are extremely important. In this context, the objective of this review was to analyze and discuss the current literature regarding the connections among these three factors-systemic diseases, endodontic infection, and endodontic dental materials-and determine how these connections may interfere in the systemic health status and the endodontic treatment outcomes, which are represented by periapical wound healing.

Assessment of Regaining Pulp Sensibility in Mature Necrotic Teeth Using a Modified Revascularization Technique with Platelet-rich Fibrin: A Clinical Study.

INTRODUCTION: The aim of the present study was to evaluate the possibility of regaining pulp sensibility in mature necrotic teeth using modified regenerative endodontic procedures by inducing bleeding in root canals and using platelet-rich fibrin (PRF). METHODS: Fifteen patients with necrotic pulp with symptomatic or asymptomatic apical periodontitis were included. At the first visit, the tooth was anesthetized, and an access cavity was performed. Mechanical preparation of root canals was performed using the standardized technique reaching apical canal preparation to K-file size #60-80. Double antibiotic paste was injected into the canal, and the cavity was temporarily sealed using glass ionomer cement. Three weeks from the first visit, regenerative endodontic procedures were performed by inducing bleeding, and a freshly prepared PRF membrane was placed in the canal. White mineral trioxide aggregate was placed directly over the PRF matrix, and the tooth was restored with a glass ionomer cement base and resin composite restoration. The electric pulp test was used to record if the teeth included in the study regained sensibility or not every 3 to 12 months follow-up. Readings at different times were compared as categoric qualitative data using the chi-square test and compared as means and standard deviations using the analysis of variance test. RESULTS: Readings of tooth sensibility revealed a highly significant difference (P < .0001) between baseline and the 12-month follow-up period. CONCLUSIONS: The presence of sensibility is indicative of the formation of vital pulplike tissue. Reestablishing real pulp tissue after regenerative endodontic treatment is debatable and still needs high level of evidence with large-scale investigations.

Healing of Apical Periodontitis after Nonsurgical Root Canal Treatment: The Role of Statin Intake.

INTRODUCTION: Numerous previously undocumented factors may influence the healing of apical periodontitis (AP). The aim of this cohort study was to analyze the association between statin medication intake during the follow-up period and healing of AP. METHODS: Patients who self-reported being on statins during nonsurgical root canal treatment or retreatment and patients who reported never taking statins were included. All patients who received treatment on a tooth with periapical radiolucency in the postgraduate endodontics clinic at the University of Maryland School of Dentistry (2011-2014) were invited for follow-up 2 to 5 years after treatment. Healing was determined using the periapical index (PAI). Two calibrated endodontists assessed outcomes blinded to the statin intake. The association of statin intake and healing of endodontic treatment (ie, healed [PAI 1-2]/not healed [PAI 3-5]) was analyzed using the Fisher exact test. Logistic regression analysis was used to explore the association between statin intake and treatment outcome, controlling for the following confounding variables: diabetes mellitus, cardiovascular disease, and smoking, with confidence intervals set at 95%. RESULTS: A total of 60 cases were included in the final analysis, including 30 patients taking statins and 30 patients not taking statins as the control. The Fisher exact test showed significantly higher healing at the 2-year or greater follow-up in patients taking statins compared with controls (93.0% vs 70%; Fisher exact test, P = .02). CONCLUSIONS: The results of this study show a significant association between long-term statin intake and healing of AP after nonsurgical root canal treatment.

[Effect of exogenous stem cells from apical papillae in the pulp revascularization treatment for the immature permanent tooth with periapical periodontitis].

Objective: To evaluate the effect of exogenous stem cells from apical papillae (SCAP) in the pulp revascularization treatment for the immature permanent tooth with periapical periodontitis in animal model. Methods: After the SCAP were isolated and cultured from the Beagle dogs, stem cell properties of these cells were characterized by analyzing their colony-forming ability, the expression of mesenchymal stem cell markers and the multidifferentiation characteristics including osteogenic, adipogenic, and chondrogenic potentials. Models of young permanent tooth with periapical periodontitis were established in dogs and the infection in each of the model tooth was eliminated by root canal irrigation and intracanal medication. After that, all of the model teeth were randomly divided into 4 groups: Group 1: normal developing teeth with no treatment applied;Group 2: teeth that periapical tissues were irritated to induce blood flowing into the root canals;Group 3: teeth that peripheral blood was delivered into the root canals;Group 4: teeth that SCAP were resuspended in peripheral blood and delivered into the root canals. In Group 2-4, firm coronal seal was performed after revascularization procedure and radiographs were taken periodically in order to observe the development of roots. After a 12-week-period, alveolar samples were collected and observed histologically. Results: The isolated SCAP showed clonogenic ability and multilineage differentiation ability including osteogenic, adipogenic and chondrogenic potentials. These cells also expressed the mesenchymal stem cell markers such as STRO-1 and CD146, while no cytokeratin was detected. The thickening of canal wall was observed radiographically 12 weeks after procedures of infection control and revascularization. Histologically, the newly formed tissues on the inner canal wall were found bone lacuna like structure in Group 2 and 3, and the new tissue formed in the Group 3 seemed easy to separate from the canal wall. The newly formed tissues in Group 4 were much thicker compare to those in the Group 2 and 3, and the dentine tubule like structure instead of bone lacuna was noticed although the orientation of these tubules were various. Conclusions: SCAP seem to play an important role in the tissue regeneration procedure when infection is well controlled in young permanent teeth with periapical periodontitis. It is difficult to achieve real tissue regeneration due to the lack of endogenous SCAP in apical area, therefore delivering adequate exogenous SCAP isolated and cultured in vitro could be a promising approach to overcome the challenge.

Endodontic medicine: interrelationships among apical periodontitis, systemic disorders, and tissue responses of dental materials

Abstract: Endodontic medicine, which addresses the bidirectional relationship between endodontic infections and systemic diseases, has gained prominence in the field of endodontics. There is much evidence showing that while systemic disease may influence the pathogenesis of endodontic infection, endodontic infection can also cause systemic alterations. These alterations include more severe bone resorption and inflammation in the periapical area as well as enhanced systemic disease symptoms. Similarly, many reports have described the impact of systemic diseases on the tissue responses to dental materials. Conversely, the local use of dental materials may show systemic effects in the form of altered production of biomarkers. Thus, studies to better understand the mechanisms related to those connections are extremely important. In this context, the objective of this review was to analyze and discuss the current literature regarding the connections among these three factors—systemic diseases, endodontic infection, and endodontic dental materials—and determine how these connections may interfere in the systemic health status and the endodontic treatment outcomes, which are represented by periapical wound healing.

Healing of Apical Periodontitis after Nonsurgical Treatment in Patients with Type 2 Diabetes.

INTRODUCTION: The purpose of this prospective study was to compare the success of primary root canal treatment between type 2 diabetic and nondiabetic patients and to investigate the effect of periapical healing on glycated hemoglobin (HbA1c) in type 2 diabetic patients with apical periodontitis. METHODS: Sixty mandibular molars with necrotic pulps and apical radiolucency (size ≥ 2 mm × 2 mm) were included in the study. Based on the HbA1c levels, patients were divided into 2 groups: type 2 diabetic (HbA1c ≥6.5%) and nondiabetic (HbA1c <6.5%). Forty-six teeth were evaluated at the 12-month follow-up time period. The primary outcome measure was the change in apical bone density as determined by the periapical index. RESULTS: Both the diabetic and nondiabetic group depicted a significant reduction in the periapical score after endodontic treatment at the 12-month follow-up (P < .05). Significantly less periapical healing was observed in the diabetic group (43%) compared with the nondiabetic group (80%) at the 12-month follow-up (P < .05). HbA1c levels in the diabetic group increased at each follow-up after endodontic treatment. CONCLUSIONS: Diabetes mellitus may have a negative impact on the outcome of endodontic treatment in terms of periapical healing. Nonsurgical endodontic treatment did not improve HbA1c levels in patients with type 2 diabetes.

Association between chronic oral inflammatory burden and physical fitness in males: a cross-sectional observational study.

AIM: To evaluate the association between chronic oral inflammatory burden (OIB) - as the combination of periodontal and endodontic disease load - and physical fitness. METHODOLOGY: One hundred and twelve nonsmoker male police officers who performed a standardized physical fitness test (PFT) were analysed. Participants underwent oral clinical and periapical radiographic examinations. Periodontal disease was assessed by probing depth (PD) and clinical attachment loss (AL). For radiographic analysis, both apical periodontitis (AP) and root canal treatment (RCT) variables were analysed. Endodontic Burden (EB) was calculated merging the total number of teeth with AP and/or RCT per individual. OIB was calculated combining EB and AL. The outcome of physical fitness was dichotomized according to whether the highest PFT score was 'achieved' or 'not-achieved'. Multivariable logistic regression models were adjusted for age, body mass index and frequency of daily exercise. RESULTS: There was no significant association between AP, RCT and EB with physical fitness whereas PD, AL and OIB were significantly associated with low physical fitness (P < 0.05). Multivariate regression analysis revealed that individuals with OIB = EB ≥ 3 and AL ≥ 4 mm had a 81% lower chance of reaching the highest PFT score (OR = 0.19, 95%CI = 0.04-0.87, P = 0.03) compared to individuals with EB < 3 and and no AL ≥ 4 mm. Individuals with unfavourable periodontal parameters but with low EB (OIB = EB < 3 & AL ≥ 4 mm) showed no significant differences on the chance to reach the highest PFT score compared to participants with favourable periodontal status and low EB (OIB = EB < 3 & no AL ≥ 4 mm). CONCLUSIONS: The OIB - higher levels of EB in periodontal patients - was independently associated with poor physical fitness in males.

Post-instrumentation pain after the use of either Mtwo or the SAF system: a randomized controlled clinical trial.

AIM: This randomized controlled trial compared the incidence of post-instrumentation pain associated with Mtwo rotary NiTi files and the self-adjusting file system following canal shaping and cleaning. METHODOLOGY: Following sample size estimation, a total of 130 patients were randomized into two groups based on selection criteria [group Mtwo and group SAF (self-adjusting file)]. Root canal treatment was carried out in two appointments. The teeth were endodontically treated with the appropriate allotted systems following the similar clinical parameters. Patients were asked to rate the intensity of pre-instrumentation and post-instrumentation pain (at 2, 4, 6, 8, 24, 48 h) using the VAS score. The Kruskal-Wallis test was carried out for the overall comparisons of the two systems. The Friedman test was used to compare between time-points with each system. Subgroup analyses for independent variables (gender, pulp status and diagnosis) used the Mann-Whitney test and Wilcoxon signed ranks test (P < 0.05). RESULTS: No significant difference was found between the two groups with respect to post-instrumentation pain. Teeth with pulpal necrosis had significant pain at 8 h compared with teeth with vital pulps (P = 0.04). Teeth with vital pulps in the SAF group had significantly less post-instrumentation pain compared with those in the Mtwo group at 6 h (P = 0.042). Patients who had teeth with nonvital pulps in the SAF group experienced more post-instrumentation pain at 8 h (P = 0.017) and 24 h (P = 0.005). CONCLUSION: The incidence of post-instrumentation pain at different time intervals in patients undergoing root canal treatment was similar for both the self-adjusting file and Mtwo file systems.

Decreased Expression of Semaphorin3A/Neuropilin-1 Signaling Axis in Apical Periodontitis.

Apical periodontitis (AP) is a chronic infection of endodontic origin accompanied with bone destruction around the apical region. Semaphorin3A (Sema3A) and neuropilin-1 (Nrp1) are regarded as a pair of immune regulators in bone metabolism. In this study, we firstly investigated the expression pattern of Sema3A/Nrp1 in apical periodontitis and its correlation with bone destruction. Using rat animal model, we analysed the level of mandibular bone destruction and the expression of Sema3A/Nrp1 on days 0, 7, 14, 21, 28, and 35 after pulp exposure. In addition, clinical samples from apical periodontitis patients were obtained to analyse the expression of Sema3A/Nrp1. These results indicated that the bone destruction level expanded from days 7 to 35. The number of positive cells and level of mRNA expression of Sema3A/Nrp1 were significantly decreased from days 7 to 35, with a negative correlation with bone destruction. Moreover, expression of Sema3A/Nrp1 in the AP group was reduced compared to the control group of clinical samples. In conclusion, decreased expression of Sema3A/Nrp1 was observed in periapical lesions and is potentially involved in the bone resorption of the periapical area, suggesting that Sema3A/Nrp1 may contribute to the pathological development of apical periodontitis.

Regenerative Characteristics of Apical Papilla-derived Cells from Immature Teeth with Pulpal and Periapical Pathosis.

INTRODUCTION: The purpose of this study was to ascertain the regenerative characteristics of apical papilla-derived cells (APDCs) from immature teeth with pulpal and periapical pathosis and thus to provide proof-of-principle evidence for further regenerative endodontic research. METHODS: Pulpal and periapical pathosis was induced in immature permanent double-rooted premolars of beagles, which were randomly assigned to experimental treatment groups: group AO (n = 14), pulp disruption and access left open; group PS (n = 14), supragingival plaque suspension-soaked cotton pellet was introduced, and access was sealed; and control (n = 7), untreated. The teeth were extracted at 2- and 4-week periods after experimental treatments. APDCs were cultured from the extracted teeth, and their cellular proliferation, differentiation characteristics, and stemness were assessed. The data were statistically analyzed. RESULTS: After 4 weeks of intentional pulpal and periapical pathosis induction period, all teeth in group PS showed features of apical periodontitis with necrotic pulp, and their APDCs showed significantly increased proliferation rate and osteogenic/odontogenic differentiation capabilities (P < .05). The stemness was maintained in all APDCs, although the stem cell population was smaller in group PS at 2-week period when the inflammatory responses were most fulminant (P < .05). CONCLUSIONS: The APDCs from immature teeth retained the regenerative characteristics with the differences according to their pulpal and periapical pathosis. The results of this study partly provide the evidence for regenerative endodontic research.