The importance of mechanosensitive cell mediated prostaglandin and nitric oxide synthesis in the pathogenesis of apical periodontitis: comparative with chronic periodontitis.

OBJECTIVES: Mechano-sensitive odontoblast cells, which sense mechanical loading and various stresses in the tooth structure, synthesize early signaling molecules such as prostaglandin E2 (PGE2) and nitric oxide (NO) as an adaptive response. It is thought that these synthesized molecules can be used for the diagnosis and treatment of periodontal and periapical diseases. The aim of this study was to investigate the relationship between the severity of apical periodontitis (AP) and chronic periodontitis (CP) and serum (s) TNF-α, IL-10, PGE2 and NO levels, as well as PGE2 and NO levels in gingival crevicular fluid (GCF) samples. MATERIALS & METHODS: A total of 185 subjects were divided into three categories: AP group (n = 85), CP group (n = 50) and healthy control group (n = 50). The AP group was divided into 3 subgroups according to abscess scoring (AS-PAI 1, 2 and 3) based on the periapical index. The CP group was divided into 4 subgroups according to the periodontitis staging system (PSS1, 2,3 and 4). After recording the demographic and clinical characteristics of all participants, serum (s) and gingival crevicular fluid (GCF) samples were taken. TNF-α, IL-10, PGE2 and NO levels were measured in these samples. RESULTS: Unlike serum measurements (sTNF-α, sIL-10, sNO and sPGE2), GCF-NO and GCF-PGE levels of the AP group were significantly higher than the control group in relation to abscess formation (54.4 ± 56.3 vs. 22.5 ± 12.6 µmol/mL, p < 0.001 and 100 ± 98 vs. 41 ± 28 ng/L, p < 0.001, respectively). Confirming this, the GCF-NO and GCF-PGE levels of the AS-PAI 1 group, in which abscesses have not yet formed, were found to be lower than those in AS-PAI 2 and 3, which are characterized by abscess formation [(16.7(3.7-117.8), 32.9(11.8-212.8) and 36.9(4.3-251.6) µmol/mL, p = 0,0131; 46.0(31.4-120.0), 69.6(40.3-424.2) and 74.4(32.1-471.0) ng/L, p = 0,0020, respectively]. Consistent with the increase in PSS, the levels of sTNF [29.8 (8.2-105.5) vs. 16.7(6.3-37.9) pg/mL, p < 0.001], sIL-10 [542(106-1326) vs. 190(69-411) pg/mL, p < 0.001], sNO [182.1(36.3-437) vs. 57.0(15.9-196) µmol/mL, p < 0.001], sPGE2 [344(82-1298) vs. 100(35-1178) ng/L, p < 0.001], GCF-NO [58.9 ± 33.6 vs. 22.5 ± 12.6 ng/L, p < 0.001] and GCF-PGE2 [ 99(37-365) vs. 30(13-119), p < 0.001] in the CP group were higher than the control group. Comparison ROC analysis revealed that the GCF-PGE2 test had the best diagnostic value for both AP and CP (sensitivity: 94.1 and 88.0; specificity: 64.0 and 78.0, respectively; p < 0.001). CONCLUSIONS: GCF-PE2 and GCF-NO have high diagnostic value in the determination of AP and CP, and can be selected as targets to guide treatment. In addition, the measurements of PGE2 and NO in GCF can be used as an important predictor of pulpal necrosis leading to abscess in patients with AP. CLINICAL RELEVANCE: In this article, it is reported that syntheses of early signaling molecules such as PGE2 and NO can be used for the diagnosis and treatment target of periapical and periodontal infections.

Enterococcus faecalis Extracellular Vesicles Promote Apical Periodontitis.

Enterococcus faecalis is an important contributor to the persistence of chronic apical periodontitis. However, the mechanism by which E. faecalis infection in the root canals and dentinal tubules affects periapical tissue remains unclear. Bacterial extracellular vesicles (EVs) act as natural carriers of microbe-associated molecular patterns (MAMPs) and have recently attracted considerable attention. In this study, we investigated the role of EVs derived from E. faecalis in the pathogenesis of apical periodontitis. We observed that E. faecalis EVs can induce inflammatory bone destruction in the periapical areas of mice. Double-labeling immunofluorescence indicated that M1 macrophage infiltration was increased by E. faecalis EVs in apical lesions. Moreover, in vitro experiments demonstrated the internalization of E. faecalis EVs into macrophages. Macrophages tended to polarize toward the M1 profile after treatment with E. faecalis EVs. Pattern recognition receptors (PRRs) can recognize MAMPs of bacterial EVs and, in turn, trigger inflammatory responses. Thus, we performed further mechanistic exploration, which showed that E. faecalis EVs considerably increased the expression of NOD2, a cytoplasmic PRR, and that inhibition of NOD2 markedly reduced macrophage M1 polarization induced by E. faecalis EVs. RIPK2 ubiquitination is a major downstream of NOD2. We also observed increased RIPK2 ubiquitination in macrophages treated with E. faecalis EVs, and E. faecalis EV-induced macrophage M1 polarization was notably alleviated by the RIPK2 ubiquitination inhibitor. Our study revealed the potential for EVs to be considered a virulence factor of E. faecalis and found that E. faecalis EVs can promote macrophage M1 polarization via NOD2/RIPK2 signaling. To our knowledge, this is the first report to investigate apical periodontitis development from the perspective of bacterial vesicles and demonstrate the role and mechanism of E. faecalis EVs in macrophage polarization. This study expands our understanding of the pathogenic mechanism of E. faecalis and provides novel insights into the pathogenesis of apical periodontitis.

The Role of Macrophage Efferocytosis in the Pathogenesis of Apical Periodontitis.

Macrophages (Mφs) play a crucial role in the homeostasis of the periapical immune micro-environment caused by bacterial infection. Mφ efferocytosis has been demonstrated to promote the resolution of multiple infected diseases via accelerating Mφ polarization into M2 type. However, the Mφ efferocytosis-apical periodontitis (AP) relationship has not been elucidated yet. This study aimed to explore the role of Mφ efferocytosis in the pathogenesis of AP. Clinical specimens were collected to determine the involvement of Mφ efferocytosis in the periapical region via immunohistochemical and immunofluorescence staining. For a further understanding of the moderator effect of Mφ efferocytosis in the pathogenesis of AP, both an in vitro AP model and in vivo AP model were treated with ARA290, a Mφ efferocytosis agonist. Histological staining, micro-ct, flow cytometry, RT-PCR and Western blot analysis were performed to detect the inflammatory status, alveolar bone loss and related markers in AP models. The data showed that Mφ efferocytosis is observed in the periapical tissues and enhancing the Mφ efferocytosis ability could effectively promote AP resolution via facilitating M2 Mφ polarization. Collectively, our study demonstrates the functional importance of Mφ efferocytosis in AP pathology and highlights that accelerating Mφ efferocytosis via ARA290 could serve as an adjuvant therapeutic strategy for AP.

Metformin switches cell death modes to soothe the apical periodontitis via ZBP1.

Apical periodontitis (AP) is a disease caused by pathogenic microorganisms and featured with the degradation of periapical hard tissue. Our recent research showed the crucial role of Z-DNA binding protein 1 (ZBP1)-mediated necroptosis and apoptosis in the pathogenesis of AP. However, the specific regulatory mechanisms of ZBP1 in AP are not fully elucidated. It was found that metformin has a regulatory role in cell necroptosis and apoptosis. But whether and how metformin regulates necroptosis and apoptosis through the ZBP1 in the context of AP remains unknown. This study provided evidence that lipopolysaccharide (LPS) promotes the synthesis of left-handed Z-nucleic acids (Z-NA), which in turn activates ZBP1. Knockout of Zbp1 by CRISPR/Cas9 technology significantly reduced LPS-induced necroptosis and apoptosis in vitro. By using Zbp1-knockout mice, periapical bone destruction was alleviated. Moreover, type I interferon induced the expression of interferon-stimulated genes (ISGs), which serve as a major source of Z-NA. In addition, the RNA-editing enzyme Adenosine Deaminase RNA specific 1 (ADAR1) prevented the accumulation of endogenous Z-NA. Meanwhile, metformin suppressed the ZBP1-mediated necroptosis by inhibiting the expression of ZBP1 and the accumulation of ISGs. Metformin also promoted mitochondrial apoptosis, which is critical for the elimination of intracellular bacterial infection. The enhanced apoptosis further promoted the healing of infected apical bone tissues. In summary, these results demonstrated that the recognition of Z-NA by ZBP1 plays an important role in AP pathogenesis. Metformin suppressed ZBP1-mediated necroptosis and promoted apoptosis, thereby contributing to the soothing of inflammation and bone healing in AP.

Outcome of nonsurgical management of large cyst-like periapical lesions using a modified apical negative pressure irrigation system: a case series study.

OBJECTIVE: To assess the effectiveness of a self-constructed modified apical negative pressure irrigation (ANPI) system employing commonly used clinical instruments in nonsurgical root canal therapy (NSRCT) for large cyst-like periapical lesions (LCPLs). METHODS: From 2017 to 2022, 35 patients diagnosed with LCPLs (5-15 mm) via preoperative clinical and radiographic evaluations of endodontic origin underwent NSRCT combined with ANPI. These patients were subjected to postoperative clinical and radiographic follow-up at 3 months, 6 months, 1 year, 2 years, 3 years, and 4 years, with a CBCT scan specifically conducted at 6-month follow-up. Through the reconstruction of three-dimensional cone beam computed tomography (CBCT) data, an early prognosis was facilitated by monitoring changes in lesion volume. Various treatment predictors-including sex, type of treatment, lesion size, preoperative pain, jaw, type of teeth involved, sealer extrusion, and the number of root canals-were meticulously analyzed. The evaluation of post-treatment outcomes leveraged both clinical observations and radiographic data collected during the follow-up periods. The Kruskal‒Wallis test and one-way ANOVA were also conducted to determine the independent factors influencing treatment outcomes. A significance level of 5% was established. RESULTS: Thirty-five teeth from 35 patients with a median age of 28 years (range 24-34) were treated; the median follow-up duration was 19 months (range 12-26). The overall success rate was 91.4%, with a median lesion reduction of 77.0% (range 54.2-96.4%) at 6 months. Patients under 30 years of age exhibited a significantly greater success rate than older patients did (100.0% vs. 80.0%, p = 0.037). Other factors, such as sex, jaw, treatment type, preoperative pain, cyst size, tooth location, sealer extrusion, and the number of roots, did not significantly impact treatment outcomes. CONCLUSIONS: Despite limitations related to the observational case-series study design and relatively small sample size, our findings suggest that utilizing the ANPI in the NSRCT for LCPLs may hold promise. The notably higher success rate in patients younger than 30 years is worth noting.

Comparation of the effectiveness of conventional needle irrigation and photon-induced photoacoustic streaming with sodium hypochorite in the treatment of teeth with apical periodontitis: a randomized clinical trial.

Photon-initiated photoacoustic streaming (PIPS) with an Er: YAG laser has been introduced in root canal treatment to improve irrigation and facilitate the removal of bacteria in the root canal system. This study aimed to compare the antibacterial effectiveness of two different root canal irrigation techniques, conventional needle irrigation (CNI) and PIPS, using 1% sodium hypochlorite (NaOCl), in the treatment of teeth with apical periodontitis. Sixty patients with a total of sixty teeth affected by apical periodontitis were included in this study. The teeth underwent root canal therapy, and after mechanical instrumentation, they were randomly assigned to two groups (n = 30) based on the final irrigation protocol: CNI or PIPS with 1% NaOCl. Bacterial suspensions in the root canals were evaluated using Adenosine 5'-triphosphate (ATP) assay kit after mechanical instrumentation and after final irrigation. Then, a follow-up was conducted after 7 days. The results revealed that final irrigation significantly reduced ATP values in both the CNI and PIPS groups (P < 0.001). The ATP values after final irrigation was greater in the CNI group compared to the PIPS group (P < 0.001). After a 7-day follow-up, percussion tenderness and fistula were significantly resolved in both groups (P < 0.05). A multivariate linear regression model was used to identify the factors that influence post irrigation ATP values. The analysis demonstrated that pre-operative percussion tenderness (P = 0.006), the presence of a fistula (P < 0.001) and the method used in the final irrigation (P < 0.001) had a significant impact on the ATP value after final irrigation. These results indicate that employing PIPS with 1% NaOCl as the final irrigation protocol exhibited superior antibacterial effectiveness and has the potential to enhance clinical outcomes in the treatment of teeth afflicted with apical periodontitis.

Prevalência de periodontites apicais e classificação do índice do complexo periapical em brasileiros por meio de tomografia computadorizada de feixe cônico / Prevalence of apical periodontitis and classification of the periapical complex index in Brazilians using cone beam computed tomography

A Periodontite Apical (PA), por ser comumente assintomática, é considerada um achado radiográfico, frequentemente encontrada em pacientes que efetuam radiografias para início ou durante tratamentos odontológicos. Entretanto, tais radiografias apresentam limitações para identificar a real extensão e destruição óssea causada pela lesão. Por isso, é indicada a realização de Tomografia Computadorizada de Feixe Cônico (TCFC). O presente estudo tem como propósito avaliar a prevalência das PA, correlacioná-las de acordo com a idade, sexo, local afetado na estrutura óssea e classificá-las de acordo como parâmetro do índice do complexo apical apresentadas em uma amostra de brasileiros, através de imagens de TCFC do banco de dados do Laboratório de Análises e Processamento de Imagens (LAPI) da Faculdade de Odontologia da Universidade de São Paulo (FOUSP). Foram analisadas 250 TCFC, utilizando o software Ondemand 3D Dental. A PA mostrou-se com prevalência maior no sexo feminino (64,53%). Em relação à localização, 232 dentes possuiam PA na maxila sendo que 140 apresentavam tratamento endodôntico satisfatório (60,34%). Na mandíbula, 96 dentes com PA, 68 apresentavam tratamento endodôntico satisfatório (70,83%). O dente mais acometido na maxila foi o 16 e na mandíbula o 46. Na comparação por sexo e condições de dentes da maxila e mandíbula, houve diferença significativa do índice R0 do dente 17, e na presença de PA no dente 25. Na mandíbula houve diferenças significativas na ausência de tratamento endodôntico do dente 42, presença de PA e índices SRD. Na análise feita por faixas etárias, não houveram diferenças significantes estatisticamente. Concluiu-se que a TCFC proporciona precisão de diagnóstico e mensurações, além de oferecer maior segurança ao cirurgião dentista.

Prevalence of Apical Periodontitis in Patients with Autoimmune Liver Diseases on Immune Suppressants and Immune Modulators: A Cross-sectional Study.

INTRODUCTION: Autoimmune liver diseases (ALDs) are chronic conditions generated by an immune-mediated autoaggressive inflammatory reaction in genetically susceptible individuals. The purpose of this study was to evaluate the prevalence of apical periodontitis (AP) in patients suffering from ALDs undergoing treatment with the immune suppressants glucocorticoids, azathioprine, and/or ursodeoxycholic acid. METHODS: The ALD group included 46 patients (11 men and 35 women, average age = 57.9 ± 11.8 years) and 1186 teeth. The control group included 50 healthy patients not taking any medications (15 men and 35 women, average age = 58.6 ± 10.4 years) and 1251 teeth. Demographic data and medical, pharmacologic, and dental history were recorded. Dental and radiographic examinations were performed. The presence of AP; the periapical index score; decayed, missing, and filled teeth; quality of restoration, and root canal treatment were evaluated. The influence of the medications the patients were taking on the prevalence of AP was also tested. RESULTS: The prevalence of AP was significantly lower in ALDs than in the control group at the patient (P = .019) and tooth level (P = .014). Smoking and age were associated with a significant increase in AP in cases and controls (P = .045 and P = .001, respectively). In both groups, endodontically treated teeth showed a higher prevalence of AP. CONCLUSIONS: Considering the limitations because of the observational nature of the study, the patients affected by ALDs liver diseases and undergoing treatment with immune suppressors (often associated with immune modulators) were found to exhibit a lower prevalence of AP.

Endodontic Microsurgery With an Autonomous Robotic System: A Clinical Report.

INTRODUCTION: Endodontic microsurgery (EMS) requires minimally invasive osteotomy and accurate root-end resection, which can be challenging in many instances. Evidence suggests that autonomous robotic systems can significantly enhance the precision of dental implantation. The aim of this case report is to introduce a novel EMS technique that employs robot-guided osteotomy and root resection procedures. METHODS: A 59-year-old man was diagnosed with previously treated, symptomatic apical periodontitis in the mandibular left first molar. Patient data were used to integrate a digital model into preoperative planning software to design the surgical plan. The robotic system utilizes spatial alignment techniques for registration, guiding the robotic arm to autonomously perform a 3-mm osteotomy and root-end resection, based on the surgical plan. After completing the resection, the clinician confirmed the absence of cracks or root fractures and subsequently performed root-end preparation and filling under a microscope. RESULTS: To the best of our knowledge, this case marks the first use of autonomous robotic assistance in EMS. CONCLUSIONS: Utilizing an autonomous robotic system could enable precise apicoectomy in patients with intact cortical plates, thus facilitating successful EMS procedures. This has the potential to minimize errors caused by operator inexperience and mitigate the risks associated with excessive bone removal.

Experimental apical periodontitis alters salivary biochemical composition and induces local redox state disturbances in the salivary glands of male rats.

OBJECTIVES: The objective was to evaluate the effects of experimental apical periodontitis on the inflammatory, functional, biochemical, and redox parameters of the parotid and submandibular glands in rats. MATERIALS AND METHODS: Twenty 12-week-old male Wistar rats were randomly divided into two groups (n = 10): a control group and apical periodontitis group. After 28 days, the saliva was collected for salivary flow rate and biochemistry composition. Both glands were sampled for quantification of the tumor necrosis factor-alpha (TNF-α) and biochemical analyses of redox state. RESULTS: TNF-α concentrations were higher in both salivary glands adjacent to the periapical lesions in animals with apical periodontitis and also compared to the control group. The apical periodontitis group increased the salivary amylase, chloride, potassium, calcium, and phosphate. The total oxidant capacity increased in the parotid gland adjacent to the periapical lesions in the same rat and compared to the control group. Conversely, the total antioxidant capacity of the parotid glands on both sides in the apical periodontitis group was lower than that in the control group. Furthermore, glutathione peroxidase activity increased in the submandibular gland adjacent to the apical periodontitis group compared to the control group. CONCLUSIONS: Experimental apical periodontitis alters salivary biochemical composition, in addition to increasing inflammatory marker and inducing local disturbances in the redox state in the parotid and submandibular glands of male rats. CLINICAL RELEVANCE: Apical periodontitis could exacerbate the decline in oral health by triggering dysfunction in the salivary glands.

Revolutionizing Endodontics: Innovative Approaches for Treating Mature Teeth With Closed Apices and Apical Lesions: A Report of Two Cases.

INTRODUCTION: Modern tissue engineering strategies have elucidated the potential of regenerative endodontic treatment (RET) as an alternative for treating mature teeth. METHODS: Here, we report two cases in which cell-based RET (CB-RET) using encapsulated allogeneic umbilical cord mesenchymal stem cells (UC-MSCs) in a platelet-poor plasma (PPP)-based scaffold was used in two mature teeth with pulp necrosis and apical periodontitis. RESULTS: After 5 years of follow-up, the healing response was satisfactory in both cases, with evidence of pulp revitalization. CONCLUSIONS: This is the first study to report the success of an extended, 5-year follow-up for allogeneic CB-RET. This report presents an innovative and sustainable solution to challenging endodontic scenarios.

Dynamically guided transantral piezoelectric endodontic microsurgery: A case report with technical considerations.

AIM: Endodontic microsurgery (EMS) of maxillary molars may represent a complex challenge to the clinician due to the location of the roots and the proximity of the maxillary sinus floor. This report aimed to describe the simultaneous use of a computer-assisted dynamic navigation (C-ADN) system and piezoelectric bony-window osteotomy for the transantral microsurgical approach of a maxillary left first molar with adequate root canal filling and symptomatic apical periodontitis. SUMMARY: This case report highlights the importance of C-ADN to carry out a minimally invasive buccal surgical access to palatal roots affected by apical periodontitis and provides a practical example to help clinicians make treatment decisions based on the available evidence. Clinical and tomographic evaluations were performed before the surgical procedure and at 24-month follow-up. This case was treated using a C-ADN system fitted to a piezotome for the buccal approach of the buccal roots, maxillary sinus membrane lifting, and for transantral location, root-end resection, cavity preparation, and filling of the palatal root. The navigation system allowed to achieve an accurate apical canal terminus location and root-end filling of the three roots with a minimally invasive piezoelectric crypt approach. At the 24-month follow-up examination, the patient remains asymptomatic, with normal periapical structures, and regeneration of maxillary sinus walls. It was concluded that the combination of dynamic navigation with piezoelectric bony-window osteotomy offers enhanced accuracy, tissue preservation, diminished risk of iatrogenic complications, and could maximize success and survival rates in transantral EMS.

Reduced C-reactive protein levels after root canal treatment in clinically healthy young apical periodontitis individuals at cardiovascular risk. A prospective study.

AIM: To determine the systemic inflammatory burden, including hsCRP and its monomeric forms, in patients with apical lesions of endodontic origin treated with root canal treatment (RCT). METHODOLOGY: Prospective pre-/post-study. Apical periodontitis (AP) individuals aged 16-40 were included (N = 29). Individuals received RCT and were followed at 1 and 6 months. Fasting blood samples were obtained. Apical lesions of endodontic origin (ALEO) diameter (mm), and periapical index (PAI), were recorded. The serum concentrations of total hsCRP were determined by turbidimetry. Tumour necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, IL-1ß, and soluble (s) E-selectin were assessed by Multiplex assay. Additionally, mCRP forms were determined in the serum of AP patients with a baseline moderate to high cardiovascular risk based on hsCRP stratification (hsCRP ≥1 mg/L) by immunowestern blot (n = 15). Also, CRP isoforms were explored in ALEOs from AP individuals (n = 4). Data were analysed with StataV16. RESULTS: Periapical index and ALEO sizes were reduced at both follow-up visits after RCT (p < .05). Serum levels of TNF-α, IL-6, IL-10, IL-1ß, and sE-selectin did not show significant differences. CRP was borderline reduced at 1 month (p = .04); however, in AP individuals at cardiovascular risk (hsCRP ≥ 1 mg/L), hsCRP and its monomeric isoform significantly decreased at 1 and 6 months (p < .05). CONCLUSIONS: High-sensitivity CRP and mCRP are reduced after RCT in AP individuals at cardiovascular risk.

Allogeneic Bone Marrow Mesenchymal Stromal Cell Transplantation Induces Dentin Pulp Complex-like Formation in Immature Teeth with Pulp Necrosis and Apical Periodontitis.

INTRODUCTION: Dental pulp regeneration is challenging in endodontics. Cellular therapy is an alternative approach to induce dental pulp regeneration. Mesenchymal stromal cells (MSCs) have the capacity to induce dental pulp-like tissue formation. In this study, we evaluated the capacity of allogeneic bone marrow MSCs (BM-MSCs) to regenerate pulp following necrosis and apical periodontitis in children's permanent immature apex teeth. METHODS: Patients aged 8 to 12 years with pulp necrosis and apical periodontitis were evaluated. The study included 15 teeth (13 incisors and 2 molars) from 14 patients (8 boys and 6 girls). Radiographic evaluation showed periapical radiolucency and immature apex teeth. There was no response to cold or electric pulp testing. The root canal of each tooth was cleaned, shaped, and Ca(OH)2 used as an interappointment medication. Cryopreserved allogeneic BM-MSCs were thawed, expanded, incorporated into preclotted platelet-rich plasma, and implanted into the tooth's pulp cavity. They were sealed with bioceramic cement and composite. Sensibility, apical foramen, calcium deposits within the root canal, and resolution of periapical lesions were evaluated in each tooth over the following 12 months. RESULTS: Based on 9 variables established for dental pulp-like tissue regeneration, all MSC-treated teeth showed evidence of successful regeneration. Clinical and radiographic evaluation of the treated teeth showed periapical lesion healing, sensitivity to cold and electricity, decreased width of the apical foramen, and mineralization within the canal space. CONCLUSIONS: Transplantation of allogeneic MSCs induces the formation of dental pulp-like tissue in permanent immature apex teeth with pulp necrosis and apical periodontitis. Implant of MSCs constitutes a potential therapy in regenerative endodontics in pediatric dentistry. Future studies incorporating a larger sample size may confirm these results.

Bone Resorption in Apical Periodontitis Enhanced by Cigarette Smoke Inhalation: Histometric, Immunohistochemical, and Microtomographic Analysis in Rats.

INTRODUCTION: This study evaluated the effects of cigarette smoke inhalation (CSI) on apical periodontitis (AP) induced in rats by histometric, immunohistochemical, and microtomographic analysis. METHODS: A total of 32 male Wistar rats were divided into 4 experimental groups (n = 8): control, CSI, AP, and CSI + AP. Rats in the CSI and CSI + AP groups inhaled cigarette smoke by remaining inside a smoking chamber for 8 minutes 3 times a day for 50 days. After 20 days of smoke inhalation, rats in the AP and CSI + AP groups had the pulp of their first right lower molar exposed to induce AP. Blood was collected on day 50 to evaluate nicotine and serum cotinine levels. The animals' mandibles were removed for histologic processing to evaluate bone resorption by histometric, immunohistochemical (receptor activator of nuclear factor kappa B ligand/osteoprotegerin), and microtomographic analysis. The Student t test was applied. RESULTS: Histometric analysis showed a larger area of bone resorption (P < .05) and microtomographic analysis found greater resorption volume (P < .001) for the CSI + AP group compared with the AP group. The CSI + AP group presented a high RANKL immunostaining pattern compared with the AP group (P < .001). CONCLUSIONS: CSI increased bone resorption caused by AP.

Periapical bacterial disinfection is critical for dental pulp regenerative cell therapy in apical periodontitis in dogs.

BACKGROUND: Application of pulp regenerative cell therapy for mature teeth with periapical lesions is a critical clinical challenge. The bacterial infection in inaccessible location within the root canal system and in the periapical lesions could cause resistance and impediment, leading to limitations in successful therapy. Thus, the aim of this study was to examine the effect of residual bacteria on the outcome of pulp regeneration in mature teeth with apical periodontitis in dogs. METHODS: Periapical lesions were induced in 32 root canals of 4 dogs in two different models in severities, model A and model B. Model A (moderate infection): the canal exposed to the oral cavity for 2 weeks and then closed for 2 weeks. Model B (severe infection): the canal exposed to the oral cavity for 2 months and then closed for 5 months. All root canals were irrigated with 6% sodium hypochlorite, and 3% EDTA and further with 0.015% levofloxacin-containing nanobubbles, which was also used as an intracanal medicament. The aseptic conditions were examined by bacterial anaerobic culture and/or PCR analyses. The root canal treatment was repeated several times, and allogeneic dental pulp stem cells were transplanted into the root canals. The radiographic evaluation of periapical lesions was performed by cone-beam computed tomography before the first treatment, just after cell transplantation, and after 2 months and 6 months in both model A, model B, respectively. The animals were then sacrificed and the jaw blocks were harvested for histological and histobacteriological evaluations of pulp regeneration and periapical tissue healing. Furthermore, the DiI-labelled DPSCs were transplanted into the root canals after complete disinfection (n = 4) or without root canal treatment (n = 4) in the apical periodontitis model (model A) in one dog, and cell localization was compared 72 h after transplantation. RESULTS: In 8 out of 12 canals from model A, and 10 out of 15 canals from model B, pulp regeneration with good vascularization, innervation, and a significant reduction in the radiolucent area of the periapical lesions were observed. However, in the other 4 canals and 5 canals from model A and model B, respectively, no pulp tissue was regenerated, and inflammation in the periapical tissue, and external resorption or healed external resorption were detected. The presence of residual bacteria in the periapical tissues and severe inflammation were significantly associated with inhibition of regenerated pulp tissue in these 9 unsuccessful canals (P < 0.05, each) (OR = 0.075, each) analyzed by multiple logistic regression analysis. For cellular kinetics, transplanted cells remained in the disinfected root canals, while they were not detected in the infected root canals, suggesting their migration through the apical foramen under the influence of inflammation. CONCLUSIONS: A true pulp-dentin complex was regenerated in the root canal by the pulp regenerative therapy in mature teeth with apical lesions. The successful pulp regeneration was negatively associated both with residual bacteria and inflammation in the periapical tissue.

Outcome of curcumin-based photodynamic therapy in endodontic microsurgery: A case report.

INTRODUCTION: Persistent apical periodontitis after root canal treatment may require surgical retreatment when non-surgical options are ineffective or impractical due to anatomical challenges or iatrogenic errors. Endodontic microsurgery (EMS) is a precise technique that aims to overcome extraradicular biofilm and root morphology issues. Photodynamic therapy (PDT) is an emerging supplementary disinfection approach that utilizes a photosensitizer agent and light to eliminate microorganisms through oxidative reactions. REPORT: A 60-year-old male with persistent apical periodontitis in a left maxillary first molar underwent non-surgical root canal retreatment followed by surgical reintervention due to anatomical complexities. During surgery, PDT was performed using a novel curcumin-based photosensitizer agent. After the procedure, the tooth was retrofilled with bioceramic cement, and photobiomodulation was applied to enhance tissue healing. One year post-surgery, the patient exhibited complete periradicular repair and remained asymptomatic. DISCUSSION: EMS is considered a last resort to salvage an endodontically treated tooth and has shown moderate success rates. PDT has demonstrated promise in improving periapical healing and reducing microorganisms. In this case, curcumin, diluted with 2 % chlorhexidine gel, served as an effective photosensitizer agent with antimicrobial properties. Moreover, performing photobiomodulation aided in cell recovery and reduced postoperative discomfort. CONCLUSION: The proposed EMS treatment protocol with PDT using curcumin yielded positive outcomes in this case report. Further randomized clinical trials are necessary to assess the efficacy of this approach in EMS. Additionally, further research on curcumin-based photosensitizer agents encapsulated in nanoparticles and enhanced antimicrobial agents is recommended to refine this treatment protocol for routine use.

Association between apical periodontitis and secondary outcomes of atherosclerotic cardiovascular disease: A case-control study.

AIM: To evaluate the association between apical periodontitis (AP) and atherosclerotic cardiovascular disease (ASCDV). METHODOLOGY: A total of 65 periodontally and systemically healthy patients (age ≥ 40 years) were included in the study. Periapical status was assessed through dental examination and periapical radiographs; 33 subjects had AP (AP+), while 32 acted as control (AP-). Moreover, data regarding their periapical index (PAI) score and the Decayed, Missing, and Filled Teeth (DMFT) index were recorded. All subjects underwent echo-colour Doppler assessment of carotid intima-media thickness (CIMT), carotid plaques, degree of stenosis using the North American Symptomatic Carotid Surgery Trial (NASCET) method, maximum diameter of the abdominal aorta (maximum AA) and common iliac arteries (CIA) diameters. Furthermore, peripheral blood flow was also measured using the ankle-brachial index (ABI). Simple and multiple regression analyses were performed. RESULTS: Among AP+ patients, 57.58% disclosed at least one sign of subclinical carotid atherosclerosis. Multiple regression analysis identified AP as a significant risk indicator for carotid plaques [OR = 4.87 (1.27, 18.98; p = .021)] and marked carotid intima-media thickenings (OR = 14.58 [1.22, 176.15], p = .035). A significant association was established between AP and other cardiovascular (CV) variables (CIMT, NASCET, and maximum AA). On the contrary, a higher PAI score does not correlate to increased odds of carotid alterations, and the presence of AP did not prove any significant change in CIA and ABI. No significant correlation was established between DMFT and other variables. CONCLUSIONS: Results from the current study highlight that the presence of AP may be regarded as a risk indicator for ASCVD, with AP being associated with 5-fold increased odds of having carotid plaques and 15-fold increased odds of having marked carotid intima-media thickenings. Further studies should be conducted in order to verify whether AP treatment could be beneficial for ASCVD signs.

A novel simplified approach for endodontic retrograde surgery in short single-rooted teeth.

BACKGROUND: High technical thresholds, long operative times, and the need for expensive and specialized equipment impede the widespread adoption of endodontic microsurgery in many developing countries. This study aimed to compare the effects of a simplified, cost-effective, and time-efficient surgical approach involving orthograde obturation using biological ceramic material greater than 6 mm combined with apicoectomy for single-rooted teeth with short lengths with those of the conventional and current standard methods. MATERIALS AND METHODS: Forty-five premolars equally categorized into three groups: conventional surgery group, standard surgery group, and modified surgery group. A µCT scan was used to calculate the volume of voids. A micro-leakage test and scanning electron microscope (SEM) were performed to assess the sealing effect. Additionally, four cases of chronic periapical periodontitis in the anterior region were selected, and the patients received either the modified approach or the standard surgery for endodontic microsurgery. RESULTS: The volumes of voids in the apical 0-3 mm of the modified group and the standard group were comparable. The micro-leakage test and SEM examination demonstrated closely bonded fillings in the dentinal walls in both the modified surgery group and standard surgery group. The outcomes of the preliminary application of this modified procedure on patients were successful at the time of the follow-up cutoff. CONCLUSIONS: The modified surgery group exhibited similar root canal filling and apical sealing abilities with the standard procedure for single-rooted teeth with short lengths (< 20 mm). The preliminary application of this modified surgical procedure achieved favorable results.

Primary apical periodontitis correlates to elevated levels of interleukin-8 in a Swedish population: A report from the PAROKRANK study.

AIM: To explore associations between root filled teeth, primary and secondary apical periodontitis, and levels of inflammatory markers in blood from patients with a first myocardial infarction and matched controls. METHODOLOGY: Between May 2010 and February 2014, 805 patients with a first myocardial infarction and 805 controls, matched for sex, age, and postal code area, were recruited to the multicentre case-control study PAROKRANK (periodontitis and its relation to coronary artery disease). All participants underwent a physical and oral examination, as well as blood sampling. Using panoramic radiography, root filled teeth, primary apical periodontitis, and secondary apical periodontitis were assessed by three independent observers. Blood samples were analysed with enzyme-linked immunosorbent assay method for the following inflammatory markers: interleukin-1ß (IL-1ß), IL-2, IL-6, IL-8, IL-12p70, tumour necrosis factor-α, and high-sensitivity C-reactive protein (hsCRP). Additionally, white blood cell count and plasma-fibrinogen were analysed. Associations between endodontic variables and the levels of inflammatory markers were statistically analysed with Mann-Whitney U-test and Spearman correlation, adjusted for confounding effects of baseline factors (sex, age, myocardial infarction, current smoking, diabetes, family history of cardiovascular disease, education, marital status, and periodontal disease). RESULTS: Mean age of the cohort was 62 years, and 81% were males. Root fillings were present in 8.4% of the 39 978 examined teeth and were associated with higher levels of hsCRP, fibrinogen, and leukocyte count, but lower levels of IL-2 and IL-12p70. After adjusting for confounders, root filled teeth remained associated with higher levels of fibrinogen, but lower levels of IL-1ß, IL-2, IL-6, and IL-12p70. Primary apical periodontitis was found in 1.2% of non-root filled teeth and associated with higher levels of IL-8 (correlation 0.06, p = .025). Secondary apical periodontitis was found in 29.6% of root filled teeth but did not relate to the levels of any of the inflammatory markers. CONCLUSIONS: This study supports the notion that inflammation at the periapex is more than a local process and that systemic influences cannot be disregarded. Whether the observed alterations in plasma levels of inflammatory markers have any dismal effects on systemic health is presently unknown but, considering the present results, in demand of further investigation.