Prevalence of apical periodontitis and non-retention of root-filled teeth in hypertensive patients: Systematic review and meta-analysis.

BACKGROUND: Several studies have suggested a relationship between AP, as well as the loss of root-filled teeth (RFT), and hypertension (HTN). OBJECTIVES: The aims of this systematic review and meta-analysis were to investigate the prevalence of AP, and non-retention of RFT, in hypertensive patients. METHODS: A search was performed in PubMed/MEDLINE, Web of Science, Scopus and EMBASE. The inclusion criteria established were studies published until February 2023, comparing hypertensive subjects with controls, assessing the prevalence of AP and/or providing data on the prevalence of non-retained RFT. Meta-analysis was performed using the RevMan (analyst) tool to determine the pooled prevalence of AP and loss of RFT. Risk of bias was assessed using the Cochrane Risk-of-Bias tool. The quality of evidence was assessed by GRADE. RESULTS: The search strategy identified 454 articles, and only eight met the inclusion criteria. Six studies had analysed the association between AP and HTN and two studies had analysed the association between non-retention of RFT and HTN. Meta-analysis showed and overall OR = 1.71 (95% CI = 0.92-3.16; p = .09) for the prevalence of AP among patients with HTN. The prevalence of non-retention of RFT among patients with HTN has an overall OR = 1.78 (95% CI = 1.60-1.98; p = .000001). The risk of bias in the individual studies was low or moderate, and the quality of the overall evidence has shown a level of certainty very low. DISCUSSION: There is no association between the prevalence of AP and HTN. In addition, hypertensive patients have significantly increased odds of losing RFT. Given the high prevalence of hypertension, it is very common to perform root canal treatments on hypertensive patients. It is imperative to communicate this heightened risk to patients and recommend periodic monitoring of oral health and hypertension, paying special attention to this subset of patients. REGISTRATION: PROSPERO CRD42022302385.

Final irrigation with bioglass solution in regenerative endodontic procedure induces tissue formation inside the root canals, collagen maturation, proliferation cell and presence of osteocalcin.

AIM: To evaluate the influence of an experimental solution of cobalt-doped F18 bioactive glass (F18Co) on tissue repair following regenerative endodontic procedure (REP) in rat molars. METHODOLOGY: The F18Co solution was prepared at a ratio of 1:5 F18Co powder to distilled water. The right or left upper first molars of 12 Wistar rats were used, where the pulps were exposed, removed, and irrigated with 2.5% sodium hypochlorite (NaOCl), followed by 17% ethylenediaminetetraacetic acid (EDTA) (5 min each). Subsequently, the molars were divided into two groups (n = 6): REP-SS and REP-F18Co, where they received a final irrigation (5 min) with saline solution (SS) or F18Co solution, respectively. Then, intracanal bleeding was induced, and the tooth was sealed. Untreated molars were used as controls (n = 3). At 21 days, the rats were euthanized, and the specimens were processed for analysis of mineralized tissue and soft tissue formation inside the root canal using haematoxylin-eosin. The presence and maturation of collagen were evaluated by Masson's trichrome and picrosirius red staining. Immunolabelling analyses of proliferating cell nuclear antigen (PCNA) and osteocalcin (OCN) were performed. The data were submitted to the Mann-Whitney U-test (p < .05). RESULTS: There was a similar formation of mineralized tissue in thickness and length in REP-SS and REP-F18Co groups (p > .05). Regarding the presence of newly formed soft tissue, most specimens of the REP-F18Co had tissue formation up to the cervical third of the canal, whilst the REP-SS specimens showed formation up to the middle third (p < .05), and there was higher maturation of collagen in REP-F18Co (p < .05). The number of PCNA-positive cells found in the apical third of the root canal was significantly higher in the F18Co group, as well as the OCN immunolabelling, which was severe in most specimens of REP-F18Co, and low in most specimens of REP-SS. CONCLUSION: The final irrigation with F18Co bioactive glass solution in REP did not influence mineralized tissue formation but induced soft tissue formation inside the root canals, with higher collagen maturation, and an increase in PCNA-positive cells and OCN immunolabelling.

Influence of dental bleaching on the pulp tissue: A systematic review of in vivo studies.

BACKGROUND: Although several studies indicate the harmful effects of bleaching on pulp tissue, the demand for this procedure using high concentrations of hydrogen peroxide (HP) is high. OBJECTIVES: To investigate the influence of bleaching on the pulp tissue. METHODS: Electronic searches were conducted (PubMed/MEDLINE, Scopus, Cochrane Library and grey literature) until February 2021. Only in vivo studies that evaluated the effects of HP and/or carbamide peroxide (CP) bleaching gels on the inflammatory response in the pulp tissue compared with a non-bleached group were included. Risk of bias was performed according to a modified Methodological Index for Non-Randomized Studies scale for human studies and the Systematic Review Centre for Laboratory Animal Experimentation's RoB tool for animal studies. Meta-analysis was unfeasible. RESULTS: Of the 1311 studies, 30 were eligible. Of these, 18 studies evaluated the inflammatory response in animal models. All these studies reported a moderate-to-strong inflammatory response in the superficial regions of pulp, characterized by cell disorganization and necrotic areas, particularly during the initial periods following exposure to 35%-38% HP, for 30-40 min. In the evaluation of human teeth across 11 studies, seven investigated inflammatory responses, with five observing significant inflammation in the pulp of bleached teeth. In terms of tertiary dentine deposition, 11 out of 12 studies noted its occurrence after bleaching with 35%-38% HP in long-term assessments. Additionally, three studies reported significant levels of osteocalcin/osteopontin at 2 or 10 days post-treatment. Other studies indicated an increase in pro-inflammatory cytokines ranging from immediately up to 10 days after bleaching. Studies using humans' teeth had a low risk of bias, whereas animal studies had a high risk of bias. DISCUSSION: Despite the heterogeneity in bleaching protocols among studies, High-concentrations of HP shows the potential to induce significant pulp damage. CONCLUSIONS: High-concentrations of bleaching gel increases inflammatory response and necrosis in the pulp tissue at short periods after bleaching, mainly in rat molars and in human incisors, in addition to greater hard tissue deposition over time. However, further well-described histological studies with long-term follow-up are encouraged due to the methodological limitations of these studies. REGISTRATION: PROSPERO (CRD42021230937).

A systematic review and meta-analysis on the effects of phototherapy on postoperative pain in conventional endodontic reintervention.

OBJECTIVES: This systematic review and meta-analysis (SRM) aimed to evaluate the efficacy of laser phototherapy (LPT) on the reduction in postoperative pain (PP) of endodontic origin after conventional/non-surgical reintervention of root canals. METHODS: This SRM was registered with PROSPERO (CRD42021243500) and followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. Meta-analysis was conducted using R software with the "META" package, the mean difference (MD) measure of effect was calculated, and the fixed effect model was applied with a 95% confidence interval (CI). The Cochrane collaboration scale was used to assess the risk of bias and the GRADE tool to assess the quality of evidence. RESULTS: Initially, 1028 articles were found, and five articles were included. Most studies were classified as "low" risk of bias. Of the five clinical studies, four showed a significant decrease in PP after endodontic reintervention in the LPT groups compared to the control group, especially in the first four days after the intervention. In symptomatic teeth with multiple roots, LPT led to less PP at 24 h (MD -0.52 [-1.03; -0.02] p = .04). However, no significant difference between the groups was found at 48 and 72 h (p > .05). The certainty of the evidence was classified as low. CONCLUSION: Despite the limitations of this SRM, LPT was shown to be a promising alternative for reducing and controlling PP in conventional endodontic reintervention. CLINICAL SIGNIFICANCE: The use of LPT in endodontic reintervention may be a safe and promising alternative to clinically efficacious agent for use in the management of PP in this procedure.

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.

Effect of ELVAX polymer subgingival implants with echistatin on extracted and reimplanted rats' teeth.

To investigate the effect of ELVAX polymer subgingival implants incorporated with echistatin peptide on incisor reimplanted tooth in rats. Forty-two male Wistars rats were divided into two groups: echistatin-treated rats (E) and control rats (C). The animals had their right maxillary incisors extracted and treated according to the International Association of Dental Traumatology replantation protocol. The extra-alveolar dry period was 30 and 60 min, and the post-surgical experimental periods were 15, 60, and 90 days. The samples were stained with H&E and analyzed for the presence of an inflammatory response, incidence of resorptions, and dental ankylosis. Results were statistically analyzed (p < 0.05). The presence of inflammatory resorption was significantly higher in group C at 30 and 60 min extra-alveolar time, in the 15-day postoperative period as compared with the E group (p < 0.05). Dental ankylosis was significantly more prevalent in group E in 30 min extra-alveolar time and 15 days postoperative period (p < 0.05). However, in 60 min extra-alveolar time and 60 days postoperative period, dental ankylosis was more prevalent in C group (p < 0.05). The use of ELVAX subgingival implants with echistatin demonstrated therapeutic potential in preventing the experimental resorption process after replantation of maxillary incisors in rats.

Increase Toll-like receptors 2 and 4 in apical periodontitis of rats with chronic liver disease.

The aim of this study was to evaluate the influence of liver fibrosis (LF) on the expression of Toll-like receptors (TLR) 2 and 4 in apical periodontitis (AP) in Wistar rats. Forty Wistar rats were allocated in the following groups (n = 10): C-control; AP-apical periodontitis; LF-liver fibrosis; AP + LF-rats with AP and LF. LF and AP were induced by established methodologies. Histological, bacteriological, and immunohistochemical analyses were performed according to pre-established scores. For comparisons between AP and AP + LF groups, the Mann-Whitney test was used (P < .05). The livers of the LF and AP + LF groups showed generalized portal inflammatory infiltrate and collagen fibers confirming the presence of LF. Histopathological analysis in the maxilla of the AP + LF group showed areas of necrosis comprising the entire dental pulp and periapical tissue surrounded by a more intense inflammatory infiltrate than observed in the AP group (P = 0.032). A significant number of specimens in the AP + LF group showed microorganisms beyond the apical foramen adhered to the extraradicular biofilm, demonstrating greater invasion compared to the AP group (P = .008). Immunohistochemical analysis showed a large number of cells immunoreactive for TLR2 and TLR4 in the AP + LF group, compared to the AP group (P < 0.05). Liver fibrosis favors the inflammation and contamination of microorganisms in apical periodontitis and triggers the expression of TLR2 and TLR4, modulating innate immunity response in periapical lesions.

Influence of bioceramic sealers on dentinal tubule penetration and antimicrobial effectiveness: a systematic review and meta-analysis of in vitro studies.

The aim of this systematic review and meta-analysis (SRM) was to evaluate whether bioceramic sealers have better penetration capacity in dentinal tubules and antimicrobial activity when compared to AH Plus® sealer. This SRM was recorded in the Open Science Framework database and followed the guidelines of the PRISMA 2020. Five databases were searched by two independent reviewers. Only in vitro studies that evaluated the effects of bioceramic sealers on dentinal tubule penetration and antimicrobial activity outcomes compared to AH Plus® sealer were included. Meta-analysis was conducted using R software, using the effect measure of the standardized mean difference (SMD) and inverse variance method. A modified Joanna Briggs Institute's Checklist was used for the risk of bias assessment. A total of 1486 studies were identified, and only 54 studies that fulfilled our eligibility criteria were included in this review. There was no statistical difference between the sealers evaluated for dentinal tubule penetration, in the thirds evaluated: coronal SMD 0.58 [0.14; 1.31], p = 0.12; middle SMD 0.07 [0.54; 0.39], p = 0.75; and apical SMD 0.08 [0.73; 0.56], p = 0.80. Both sealers demonstrated similar antimicrobial action (SMD [3.42; 5.32], p = 0.67 and SMD 0.67 [1.89; 0.55], p = 0.28). The studies presented a low risk of bias. Based on the in vitro studies included and according to the limitations of the present review, the data suggest that bioceramic and AH Plus® sealers present similar penetration capacity in dentinal tubules and antimicrobial effect, making them suitable materials to be considered in clinical practice.

Influence of systemic antibiotic therapy on the development and progression of induced apical periodontitis in Wistar rats.

The aim of this study was to investigate the influence of systemic antibiotic therapy on the development and progression of induced apical periodontitis (AP) in Wistar rats. Fifty-six rats were submitted to pulp exposure of the lower left first molar for the induction of AP. On the same day, intraperitoneal antibiotic therapy was administered once a day, for 15 days, until euthanasia. The groups were formed according to the different treatments (n = 8): C-control; GEN-treated with gentamicin (10 mg/Kg); AC-treated with amoxicillin (100 mg/Kg); MZ-treated with metronidazole (40 mg/Kg); AMP-treated with ampicillin (100 mg/Kg); AMC group-treated with amoxicillin + clavulanic acid (100 mg/kg); CLI-treated with clindamycin (60 mg/kg). After euthanasia, the jaws were collected and processed for (1) histological and histometric analysis using hematoxylin and eosin staining, (2) analysis of collagen fibers using Picrosirius Red staining and (3) bacteriological analysis using Brown-Brenn staining. The data were analyzed statistically (p < 0.05). AP induction was confirmed in all groups. The AMC group had the lower intensity of inflammatory infiltrate (p = 0.028) and less periapical bone resorption compared to control (p = 0.006). Regarding collagen maturation, PSR staining revealed a predominance of mature collagen fibers in all groups. The AC and AMC groups had the lower amount of mature fibers and the highest amount of immature fibers, compared to all other groups (p < 0.001). All groups showed bacterial contamination; however, the AC and AMC groups showed a lower extent of bacterial contamination compared to the control (p < 0.001). It can be concluded that systemic antibiotic therapy influences the development and progression of induced AP.

TNFSF13B rs9514828 gene polymorphism and soluble B cell activating factor levels: Association with apical periodontitis.

AIM: The aim of this case-control study was to evaluate the association between the TNFSF13B rs9514828 (-871 C > T) polymorphism and soluble BAFF (sBAFF) in apical periodontitis (AP) patients. METHODOLOGY: Two hundred and sixty one healthy subjects (HS) and 158 patients with AP classified as: 46 acute apical abscess (AAA), 81 primary AP (pAP) and 31 secondary AP (sAP) patients were included. Genomic DNA (gDNA) was extracted from peripheral blood cells according to the salting out method. The TNFSF13B rs9514828 (NC_000013.11:g.108269025C > T) were identified using polymerase chain reaction (PCR) followed by restriction fragment length polymorphisms (RFLP). Serum sBAFF levels were measured by ELISA test. The chi-squared or Fisher's exact test was performed. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated to evaluate the risk of AP associated with the rs9514828. The Mann-Whitney U test and Kruskal-Wallis analysis were used for non-normally distributed data. Differences were considered significant with a p-value <.05. RESULTS: No differences in the genotype/allele frequencies were shown between HS and patients with AAA. However, the TT genotype (OR = 2.68, 95% CI: 1.10-6.53; p = .025) and T allele (OR = 1.46, 95% CI: 1.00-2.12; p = .045) were associated with increased risk of pAP. In contrast, the minor allele T significantly decreased the risk of sAP (OR = 0.49, 95% CI: 0.024-0.99; p = .043). sBAFF serum levels were increased in AAA and pAP compared with HS (p < .01 and p = .021, respectively). The AAA patients had higher sBAFF serum levels than pAP (p = .034) and sAP (p < .01). CONCLUSIONS: These results suggest that the TNFSF13B rs9514828 (-871 C > T) polymorphism is associated with pAP susceptibility and that BAFF is a cytokine that might be involved in acute and chronic AP. The future exploration of the rs9514828 polymorphism in other AP cohorts is recommended.

Inflammatory profile of apical periodontitis exacerbated by cigarette smoke inhalation: Histological and immunohistochemical analysis in rats.

AIM: The aim of this study was to evaluate the effects of cigarette smoke inhalation (CSI) on inflammation, pro-inflammatory mediators and haematological parameters in rats with induced apical periodontitis (AP). METHODOLOGY: Thirty-two 3-month-old male Wistar rats were divided into four experimental groups (n = 8): C-Control; S-rats with CSI; AP-rats with AP; and SAP-rats with CSI + AP. Animals in groups S and SAP inhaled cigarette smoke by remaining inside a smoking chamber for 8 min, three times daily, for 50 days. After 20 days of smoke inhalation, animals in AP and SAP groups had the pulps of the lower right first molar exposed to oral environment for 30 days to induce AP. In these subsequent 30 days, animals in group S and SAP continued with CSI. On Day 50, animals were euthanized and mandibles were histologically processed to assess inflammatory infiltrate, immunohistochemical interleukins (IL-1ß, IL-6 and TNF-α), and blood samples collected for laboratory analysis. The Mann-Whitney test was performed for non-parametric data and the pairwise analyses of Student's t-test for parametric data, with a significance level of p < .050. RESULTS: Inflammatory infiltrate was moderate in AP group and more severe in the SAP (p = .010). The interleukins IL-6, IL-1ß and TNF-α were higher in SAP group (p < .001) when compared to the AP group. A greater number of red blood cells (p = .010), haemoglobin (p = .007) and neutrophils (p = .014) were observed in the SAP group in comparison with the AP group. CONCLUSION: Cigarette smoke inhalation induced a more severe inflammatory infiltrate, with increased levels of pro-inflammatory cytokines and changes in haematological parameters in rats with induced AP. Thus, CSI aggravated AP, exacerbating the inflammatory response.

Influence of ethylenediaminetetraacetic acid irrigation on the regenerative endodontic procedure in an immature rat molar model.

AIM: To analyse the influence of ethylenediaminetetraacetic acid (EDTA) on the repair process in immature rat molars after a regenerative endodontic procedure (REP). METHODOLOGY: The lower first molars of 12 4-week-old Wistar rats underwent pulpectomy in the mesial root and were divided into the following groups: sodium hypochlorite (NaOCl; n = 6) - the mesial canals were irrigated with 2.5% NaOCl for 5 min, and NaOCl-EDTA (n = 6) - the canals were irrigated with 2.5% NaOCl, followed by 17% EDTA for 5 min each. After evoking bleeding using a size 10 K-file, the cavities were sealed. Three molars on the untreated side were randomly used as control (control-15 d; n = 3), and three molars from the other three rats untreated were used as immediate control (n = 3). After 15 days (NaOCl, NaOCl-EDTA and control-15 d groups) or immediately (control-immediate), the animals were euthanized, and the teeth were subjected to histologic evaluation of tissue regeneration and presence of collagen fibres. Mann-Whitney U-test was used (p < .05). RESULTS: The experimental groups had newly formed cementum-like tissue and increased root length and thickness. Half of the specimens in NaOCl-EDTA group showed apical foramen closure, whilst the NaOCl group had partial apical closure. The experimental groups showed inflammatory infiltrate extending mainly to the medium third of the root canal. These parameters were similar between experimental groups (p > .05). Newly formed connective tissue in the pulp space was significantly higher in the NaOCl-EDTA group than in NaOCl group (p < .05). Regarding the collagen fibres, the NaOCl-EDTA group had more collagen fibres in the root tip, but there was no significant difference compared to NaOCl group, and both groups showed greater amount of immature fibres in this area; in the centre of the apical third of root canal, there was equivalence between mature and immature fibres from both groups (p > .05). CONCLUSIONS: Ethylenediaminetetraacetic acid irrigation improved newly formed intracanal connective tissue after REP in immature molars of rats; however, EDTA did not influence cementum-like tissue formation, apical closure, inflammatory infiltrate and maturation of collagen fibres.

Effects of cigarette smoke inhalation on the immune-inflammatory profile of experimental apical periodontitis in rats.

OBJECTIVE: To evaluate the effects of cigarette smoke inhalation on the immune-inflammatory profile of experimental apical periodontitis in rats. METHODOLOGY: In total, 32 male Wistar rats were divided into four groups (n = 8): AP-induced apical periodontitis; S-cigarette smoke inhalation; APS-induced AP and cigarette smoke inhalation; and C (control)-neither AP nor cigarette smoke inhalation. To induce cigarette smoke inhalation, the animals were kept in a chamber filled with tobacco smoke for 8 min thrice a day for 50 days. AP was induced 20 days after inhalation initiation by exposing their coronary pulp to their oral environment for 30 days. After animals were euthanized, their right hemimaxillae were removed for histopathological, semi-quantitative and immunohistochemical (F4/80, CD206 and iNOS) analyses. RESULTS: Quantitative data showed a moderate number of inflammatory infiltrates in AP and an intense number in APS (p < .05). Comparing F4/80+ cells showed no statistically significant differences among groups, but we found more CD206+ cells in AP than in C and S (p > .05). INOS+ immunostaining showed a significant increase in AP and APS, when compared with C and S (p < .05). APS had more iNOS+ cells than AP (p < .05). CONCLUSION: Cigarette smoke inhalation worsened AP, leading to a predominantly pro- inflammatory profile in our experimental model.

Melatonin decreases plasma TNF-α and improves nonenzymatic antioxidant defence and insulin sensitivity in rats with apical periodontitis fed a high-fat diet.

AIM: To analyse the effects of melatonin (ME) treatment on oxidative stress and insulin resistance (IR) in rats with apical periodontitis (AP) fed a high-fat diet (HFD). METHODOLOGY: Eighty 60-day-old rats were divided into eight groups: control (CN), AP, HFD with AP (HFDAP), control with ME (CNME), AP with ME (APME), HFD with ME (HFDME) and HFD with AP+ME (HFDAPME). The animals from the HFD groups were fed a HFD throughout the experimental period. On day 7, the animals from the AP groups were subjected to experimental AP, and after 70 days, the ME groups were treated for 30 days. Glycaemia, insulinaemia, homeostatic model assessment for IR index, tumour necrosis factor-α (TNF-α), and interleukin-6 were analysed in plasma using biochemical tests and enzyme-linked immunosorbent assay. Thiobarbituric acid-reactive substances (TBARS), carbonyl protein (CP), superoxide dismutase (SOD), catalase, glutathione peroxidase, glutathione (GSH) and total antioxidant capacity (ferric reducing antioxidant power [FRAP]) were analysed in the gastrocnemius muscle. RESULTS: (1) Association of AP and HDF exacerbated IR, and ME treatment improved this alteration; (2) AP and HFD and their association showed increased TNF-α, and ME reversed it; (3) TBARS increased in the AP and HFDAP groups, and ME reversed only in the group with the association of disease and diet; (4) CP increased in all HFD groups and improved in the ME groups; (5) GSH activity decreased in all experimental groups, and ME increased this parameter only in the CN and AP groups; (6) FRAP did not change between the groups, but ME treatment increased its activity in the AP and HFD groups; (7) ME increased SOD in the CN and AP groups. CONCLUSION: Apical periodontitis and HFD promoted IR, and the association of AP with diet promoted IR exacerbation; this resistance might have been caused by an increase in TNF-α. AP promoted more intense changes in lipid oxidative damage than in protein oxidative damage. In non-enzymatic antioxidant defence, it was observed that both AP and HFD and their association promoted a decrease in GSH levels. Overall, ME treatment reversed changes such as oxidative stress and IR.

Early life stress exacerbates bone resorption and inhibits anxiety-like behaviour induced by apical periodontitis in rats.

AIM: To evaluate the influence of the early life stress (ELS) on the severity of the apical periodontitis (AP) in Wistar rats. METHODOLOGY: Forty male Wistar rats were divided into four groups (n = 10): Control rats; AP-rats with AP; ELS-rats subject to ELS; AP + ELS-rats exposed to ELS and subject to AP. ELS was induced by maternal separation (MS) for a period of 3 h for 21 consecutive days. AP was induced via pulp exposure of the first and second right maxillary molars to the oral environment for 40 days. Three days before euthanasia, all rats underwent behavioural analysis to measure anxiety levels by elevated zero maze. Then, the rats were euthanized and the maxillas were removed to assess the occurrence and severity of AP. The periapical region was evaluated for the intensity of the inflammatory infiltrate and the extent of bone loss. The Mann-Whitney test was performed for nonparametric data, and the Tukey's or Student's t-test was performed for parametric data (p < .05). RESULTS: The intensity of the inflammatory infiltrate was significantly larger in the AP + ELS group when compared with AP group (p < .05). The AP + ELS group exhibited significantly greater alveolar bone loss, with a periapical lesion size of 103.5 ± 29.88, compared with 72.3 ± 22.28 in the AP group (p < .05). Rats with AP displayed higher anxiety-like behaviour in relation to the control group (p < .05). However, exposure to ELS abolished the AP-induced increased anxiety-like 'behaviour' throughout, since that rats from AP + ELS group attended more the open arms than non-stressed rats with AP (p < .05). CONCLUSION: Early life stress is predictive of the severity of AP exacerbating the inflammatory process and increasing periapical bone resorption.

Antimicrobial effectiveness of ultrasonic irrigation in root canal treatment: a systematic review of randomized clinical trials and meta-analysis.

OBJECTIVE: The objective of this systematic review and meta-analysis (SRM) was to answer the question as to whether the use of ultrasonic irrigation (UI) results in better antimicrobial activity in root canal disinfection compared to conventional irrigation (CI). METHODS: A literature search was performed in the main scientific databases, carried out until October 2021. The eligibility criteria were randomized clinical trials (RCTs). Two meta-analyses were conducted using R software with the "META" package. The mean difference (MD) and odds ratio (OR) measure of effect were calculated. The fixed effect model was applied with a 95% confidence interval. The Cochrane collaboration scale was used to assess risk of bias and the GRADE tool to assess the quality of evidence. RESULTS: A total of 1782 records were screened, and 12 studies meeting the criteria were included in this review. A low risk of bias was observed for most domains, except allocation concealment that was considered unclear. The certainty of evidence was classified as moderate in the OR meta-analyses and low in the MD meta-analyses. Ultrasonic irrigation resulted in a better antimicrobial effect in both meta-analyses, MD 1.42 [1.60; 1.23] p < 0.0001, I2 = 80%; and OR 3.86 [1.98; 7.53] p< 0.0001, I2 = 28.7%. CONCLUSION: Within the limitations of this SRM, UI presented better antimicrobial efficacy than CI. CLINICAL RELEVANCE: UI should be used by clinicians as it promotes better antimicrobial efficacy in patients undergoing endodontic treatment.

Interleukin-6, tumor necrosis factor-α, and CD5 immunolabeling of new experimental endodontic sealer and repair material.

The aim of this study was to evaluate the biocompatibility and immunoinflammatory response of the Sealepox and Sealepox-RP, based on interleukin (IL)-6, tumor necrosis factor (TNF)-α, and CD5 immunolabelling. The ProRoot MTA (PRMTA) was used for comparison. Polyethylene tubes (1.0-mm internal, 1.6-mm external diameter, and 10.0-mm length; ISO 10993) with or without (control) materials were randomly implanted in the dorsum of 35 rats (4 per rat). After 7, 15, 30, 60, and 90 days (n = 7), the tubes were removed for histological and immunohistochemical analysis. The Kruskal-Wallis and Dunn's test for non-parametric data and, ANOVA and Tukey test for parametric data were used (P < 0.05). Hematoxylin and eosin staining revealed that the concentration of inflammatory cells decreased over time with no differences between groups in all periods (P > 0.05). Regarding IL-6 immunostaining, there was no difference at 7 days (P > 0.05); all groups decreased over time, being faster for the PRMTA group and also, with no differences between groups in the last period (P > 0.05). For TNF-α, at 7 days there was no difference between groups (P > 0.05); there was an increase at 15 days for PRMTA and, at 30 and 60 days, for PRMTA and Sealepox compared to the control (P < 0.05). At 90 days, Sealepox RP showed the lowest immunostaining being similar to the control (P > 0.05). Regarding CD5 cells, at 7 days, there was high immunostaining for PRMTA compared to the control (P < 0.05); and significant reduction over time with difference for all groups at 30 and 60 days. (P < 0.05); Sealepox was similar to the control in all periods (P > 0.05). Sealepox RP showed the highest immunostaining at 15 days, being different from the control and PRMTA (P < 0.05); in the other periods it was similar to the control (P > 0.05). It can be concluded that Sealepox and Sealepox-RP were biocompatible and demonstrated similar immunoinflammatory response regarding IL-6, TNF-α, and CD5 compared to PRMTA.

Postoperative pain after root canal filling with bioceramic sealers: a systematic review and meta-analysis of randomized clinical trials.

The aim of this systematic review and meta-analysis (SRM) was to assess postoperative pain (PP) after endodontic treatment with bioceramic root canal sealer compared to AH Plus® sealer. This SRM was carried out in accordance with the items on the PRISMA 2020 checklist and Cochrane guidelines and registered in PROSPERO (CRD42021259283). Only randomized clinical trials (RCTs) were included. Meta-analysis was conducted using R software, the standardized means difference (SMD) measure of effect was calculated for quantitative variables, and the odds ratio (OR) for binary variables. The Cochrane tool (RoB 2.0) was used to assess the risk of bias, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the quality of evidence. Qualitative and quantitative analysis included 18 and 17 studies, respectively. For quantitative variables, the bioceramic root canal sealer presented less occurrence of postoperative pain than the AH Plus® sealer in 24 h (SMD - 0.17 [- 0.34; - 0.01], p = 0.0340). For binary variables, there was no difference observed between the sealers evaluated, except for sealer extrusion where the bioceramic group had lower post-filling material extrusion (OR 0.52 [0.32; 0.84], p = 0.007). Regarding the risk of bias analysis, low risk was observed for most domains, except allocation that was considered unclear, while the certainty of evidence ranged from moderate to low. The results showed that bioceramics sealers reduced postoperative endodontic pain only after 24 h and showed less sealer extrusion compared to the AH Plus® sealer. However, more robust and standardized clinical trials are needed to confirm the results with less heterogeneity and higher quality of evidence.

Melatonin decreases IRF-3 protein expression in the gastrocnemius muscle, reduces IL-1ß and LPS plasma concentrations, and improves the lipid profile in rats with apical periodontitis fed on a high-fat diet.

To evaluate the effects of melatonin (MEL) on the expression of toll-like receptor-4 (TLR4); myeloid differentiation primary response protein-88 (MyD88); TIR-domain-containing adapter-inducing interferon-ß (TRIF); IFN regulatory-factor-3 (IRF-3); nuclear factor kappa-B (NF-κB); plasma concentrations of interleukin-1ß (IL-1ß) and lipopolysaccharide (LPS); and lipid profile of rats with apical periodontitis (AP) fed on a high-fat diet (HFD). Eighty 60-day-old rats were divided into eight groups: control, AP, HFD, HFDAP, CNMEL, APMEL, HFDMEL and HFDAPMEL. HFD groups were fed on a HFD for 107 days. On day 7, experimental AP was induced in the AP groups, and after 70 days, MEL (5 mg/kg) was administered to the MEL groups for 30 days. Plasma concentrations of LPS and IL-1ß were analyzed using enzyme-linked immunosorbent assay, and the lipid profile was analyzed using biochemical tests. The expression of proteins involved in the TLR4 pathway (TLR4, MyD88, TRIF, IRF-3 and NF-κB) in the gastrocnemius muscle (GM) was evaluated using western blotting and qRT-PCR. Treatment with MEL decreased IRF-3 protein expression in GM and IL-1ß plasma concentration in the APMEL and HFDMEL groups. Reduction in LPS plasma concentration was reported only in the HFDMEL group. Additionally, a decrease in LDL and an increase in HDL were observed in the HFDMEL and HFDAPMEL groups. Treatment with MEL exhibited anti-inflammatory and anti-hyperlipidemic effects attributed to HFD and AP by reducing the plasma concentrations of IL-1ß and LPS in addition to reducing IRF-3 protein expression in the GM, which is associated with the production of inflammatory cytokines.

Melatonin as an adjunctive treatment on dental procedures: A systematic review.

The systematic review tried to answer the following question: Does the melatonin administered systemically or topically ameliorate patients involved with oral health conditions or dental procedures? The systematic review has been registered in the PROSPERO (2021CRD42021095959). Eligibility criteria included only randomized controlled clinical trials (RCTs) with at least 10 participants that compared patients that received melatonin as a treatment before and/or after their oral intervention topically or systemically, with control patients. A search was performed in PubMed/MEDLINE, Web of Science, Cochrane Library, and Academic Google databases for articles up to February 2021. The Cochrane risk-of-bias tool for randomized clinical trials was used and revealed that the studies included presented low risk of bias for the majority of criteria assessed. It was selected 25 articles, of which only six did not demonstrate positive effects and three presented null effects with the use of melatonin. Melatonin has improved the inflammatory response in periodontal disease, dental surgeries, and mucositis of head and neck oncologic irradiated patients. In addition, it showed anxiolytic potential in patients that were submitted to dental procedures. In conclusion, melatonin favored the treatment of oral changes when used topically and systemically.