Impact of N-acetylcysteine (NAC) and calcium hydroxide intracanal medications in primary endodontic infection: a randomized clinical trial.

OBJECTIVES: This RCT investigated the impact of N-acetylcysteine (NAC) and calcium hydroxide [Ca(OH)2] intracanal medications (ICMs) in primary endodontic infection with apical periodontitis (PEIAP). MATERIALS AND METHODS: Thirty-six teeth with PEIAP were randomly divided into groups according to the ICM: NAC, Ca(OH)2 + saline solution (SSL), and Ca(OH)2 + 2% chlorhexidine-gel (2% CHX-gel) (all, n = 12). Root canal samples (RCSs) were collected before (s1) and after instrumentation (s2) and after 14 days of ICM (s3). Chemomechanical preparation (CMP) was performed with a Reciproc file and 2.5% NaOCl. Checkerboard DNA-DNA hybridization was used to assess 40 target bacteria species. RESULTS: At s1, bacterial DNA was detected in 100% of RCSs (36/36). All 40 bacterial species were found in PEIAP. The mean number of species per RCS was 17.92 ± 13.18. The most frequent bacteria were S. mitis (65%), E. nodatum (63%), E. faecalis (63%), F. nucl sp vicentii (58%), T. forsythia (58%), and F. periodonticum (56%). CMP reduced the mean number of species per RCS to 6.8 ± 2.36 (p < 0.05). At s3, the intragroup analysis revealed a broader antimicrobial activity for Ca (OH)2 + 2% CHX-gel and NAC than Ca(OH)2 + SSL (p < 0.05). NAC eliminated 8/12 bacteria species resistant to both Ca (OH)2 ICMs, including P. micra, P. nigrescens, T. denticola, A. israelii, P. endodontalis, P. acnes, C. ochracea, and E. corrodens. CONCLUSIONS: Ca (OH)2 + 2% chlorhexidine gel (2% CHX gel) showed a greater bacterial elimination over the number of bacterial species; however, NAC eliminated 8/12 bacteria species resistant to both Ca (OH)2 ICMs (RBR-3xbnnn). CLINICAL RELEVANCE: The use of intracanal medication with a broad antimicrobial activity can optimize root canal disinfection. Ca(OH)2 + 2% CHX gel and NAC showed a broader antimicrobial activity than Ca(OH)2 + SSL against endodontic pathogens in primary root canal infection. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials (REBEC), No. RBR-3xbnnn.

Effects of Calcium Hydroxide Intracanal Medications on T Helper (Th1, Th2, Th9, Th17, and Tfh) and Regulatory T (Treg) Cell Cytokines in Apical Periodontitis: A CONSORT RCT.

INTRODUCTION: This Consolidated Standards of Reporting Trials randomized clinical trial investigated T helper (Th1, Th2, Th9, Th17, and Tfh) and regulatory T (Treg) cell-type cytokines and their networks in apical periodontitis (AP). We also assessed the effects of calcium hydroxide [Ca(OH)2] intracanal medications (ICMs) on helper T and Treg cell-type cytokines. METHODS: Twenty teeth with primary endodontic infection and apical periodontitis were randomly divided into two groups: Ca(OH)2 + saline solution (n = 10) and Ca (OH)2 + 2% chlorhexidine-gel (n = 10). Samples were collected from the periradicular tissue fluid (PTF) before (PTFs1) and after 14 days of ICMs (PTFs2). The Human High Sensitivity T Cell Panel was used to quantify target T-helper (Th)1: interelukin (IL)-2, IL-12, and interferon-gamma (IFN-γ); Th2: IL-4, IL-5, and IL-13; Th9: IL-9; Th17: IL-17; T follicular helper cells (Tfh): IL-21; and Treg-cell-type cytokine: IL-10. RESULTS: Th1-type cytokines were higher than Th2-type ones, at PTFs1. Positive (+) associations were found among all Th1-type cytokines and all Th2-type cytokines. There were negative (-) correlations between all Th1- and Th2-type cytokines. Size of radiolucent lesions and symptoms (tenderness to percussion and/or pain on palpation) were positively correlated with Th1-type cytokines, IL-17, and IL-21 but negatively correlated with Th2-type cytokines and IL-10 (all, P < .001). Both ICMs increased Th2-type cytokines and IL-10 (P < .05) and decreased Th1-type cytokines, IL-17, and IL-21 (P < .05), with no differences among them (P > .05). CONCLUSIONS: Complex T-cell cytokine networks are involved in AP. Both Ca(OH)2 ICMs effectively increased IL-4, IL-5, IL-10, and IL-13 and lowered IL-2, IL-12, IL-17, IL-21, and IFN-γ.

Comparison of GentleWave system and passive ultrasonic irrigation with minimally invasive and conventional instrumentation against LPS in infected root canals.

This study compared the effectiveness of GentleWave system (GWS) and passive ultrasonic irrigation (PUI) in removing lipopolysaccharides (LPS) from infected root canals after minimally invasive (MIT) and conventional instrumentation (CIT) techniques. Sixty first premolars with two roots were inoculated with fluorescent LPS conjugate (Alexa Fluor 594). Of those, twelve were dentin pretreated, inoculated with fluorescent LPS conjugate, and submitted to confocal laser scanning microscopy (CLSM) to validate the LPS-infection model. Forty-eight teeth were randomly divided into treatment groups: GWS + MIT, GWS + CIT, PUI + MIT, and PUI + CIT (all, n = 12). Teeth were instrumented with Vortex Blue rotary file size 15/0.04 for MIT and 35/0.04 for CIT. Samples were collected before (s1) and after a root canal procedure (s2) and after cryogenically ground the teeth (s3) for intraradicular LPS analysis. LPS were quantified with LAL assay (KQCL test). GWS + MIT and GWS + CIT were the most effective protocols against LPS, with no difference between them (p > 0.05). PUI + CIT was more effective than PUI + MIT (p < 0.05) but less effective than GWS + MIT and GWS + CIT. GWS was the most effective protocol against LPS in infected root canals using MIT and CIT techniques.

Clinical influence of calcium hydroxide intracanal medications on matrix metalloproteinases and tissue inhibitors of metalloproteinases in apical periodontitis.

OBJECTIVES: This study investigated the influence of calcium hydroxide intracanal medications on the levels of metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in apical periodontitis (AP). MATERIALS AND METHODS: Twenty primarily infected root canals with AP were randomly divided into two groups: Ca(OH)2 + sterile saline solution (SSL) group and Ca(OH)2 + 2% chlorhexidine gel (CHX gel) group. We collected samples from the periradicular tissue fluid (PTF) before (s1) and after 14 days of intracanal medication (s2). MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 were measured by ELISA assay. RESULTS: MMP-1, MMP-2, MMP-9, TIMP-1, and TIMP-2 were detected in all PTF samples at s1 and s2 (20/20). At s1, MMP-2 and MMP-9 were detected at higher levels than MMP-1 (p < .05). Higher levels of TIMP-1 than TIMP-2 were found in AP (p < .05). Additionally, we detected higher MMP-1, MMP-2, and MMP-9 over TIMP-1 and TIMP-2 levels in AP (p < .05). At s2, Ca(OH)2 + SSL was as effective as Ca(OH)2 + 2% CHX gel in lowering the levels of MMP-1, MMP-2, and MMP-9 after 14 days of intracanal medication, with no significant difference between them (p > .05). Both Ca(OH) 2 intracanal medications had no significant impact on the levels of TIMP-1 and TIMP-2 (both p > .05). At s2, TIMP-1 levels were higher than TIMP-2 (p < .05). Moreover, there were positive correlations between the levels of MMP-1 and TIMP-1 and MMP-1 and TIMP-2 (p < .05). CONCLUSIONS: Calcium hydroxide medications effectively lowered the levels of MMP-1, MMP-2, and MMP-9 in periapical tissues after 14 days of treatment, with no difference between them. Moreover, the calcium hydroxide intracanal medications tested here had no impact in TIMP-1 and TIMP-2 in periapical tissues. CLINICAL RELEVANCE: MMPs and TIMPs play an essential role in the degradation of the extracellular matrix. The imbalance MMPs and TIMPs can cause periapical tissue destruction. Therefore, the reestablishment of the balance between activated MMPs and TIMPs with root canal therapy is essential to restore tissue homeostasis.

Comparison of the effectiveness of single- and multiple-sessions disinfection protocols against endotoxins in root canal infections: systematic review and meta-analysis.

This systematic review (SR) addressed the following common clinical question: What is more effective in reducing or eliminating endotoxin in endodontic infections-single or multiple-session treatments using calcium hydroxide medications? Literature searches of Medline/PubMed, Embase, Cochrane Library, Scielo, Science Direct, Web of Knowledge, Scopus, and Google Scholar databases. Two reviewers independently assessed the eligibility for inclusion, extracted data, and evaluated the quality of the studies using the risk of bias tools. Electronic searches resulted in 358 articles, of which 32 studies were included for full-text assessment, and nine were included in this review. Meta-analysis pooling all the nine studies revealed lower levels of endotoxin for multiple-session treatment (P < 0.001). The sub-group analysis indicated no difference between single-session and 7 days of Ca(OH)2 medication (SMD - 0.32; P = 0.22). However, 14-days (I2 = 80.5%, P < 0.001) and 30-days (I2 = 78.9%, P < 0.01) of Ca(OH)2 medication was more effective than single-session treatment (both, p < 0.001). Overall, Overall, this SR provides evidence to support that multiple-session disinfection protocols with the placement of Ca(OH)2 medications are more effective in reducing the levels of endotoxin from root canal infections compared to single-session when applied for 14 and 30 days.

Does supplemental photodynamic therapy optimize the disinfection of bacteria and endotoxins in one-visit and two-visit root canal therapy? A randomized clinical trial.

AIM: To evaluate the effectiveness of supplemental photodynamic therapy (PDT) in optimizing the removal of bacteria and endotoxins from primarily infected root canals after one-visit and two-visit treatments. METHODOLOGY: Twenty-four primarily infected root canals with apical periodontitis were selected and randomly divided into one-visit (n=12) and two-visit treatment groups (n=12). Chemo-mechanical preparation (CMP) was performed by using the single-file reciprocating technique+2.5% NaOCL and a final rinse with 17% EDTA. The photosensitizer agent (methylene blue 0.1mg/mL) was applied to root canals for 60s before application of laser with a potency of 60mW and energy density of 129J/cm2 for 120s after CMP in the one-visit treatment and after 14-day inter-appointment medication with Ca(OH)2+Saline solution (SSL) in the two-visit treatment. Samples were collected before and after root canal procedures. Endotoxins were quantified by chromogenic limulus amebocyte lysate assay. Culture techniques were used to determine bacterial colony-forming unit counts. RESULTS: Bacteria and endotoxins were detected in 100% of the initial samples, with median values of 1.97×105 CFU/mL and 24.983EU/mL, respectively. The CMP using single-file reciprocating technique was effective in the reduction of bacteria and endotoxins (All, p<0.05). The supplemental PDT was effective in reducing bacterial load in the one-visit (p<0.05) but not in the two-visit treatment after use of Ca(OH)2 medication for 14days (p>0.05). In the two-visit group, after 14days of inter-appointment medication with Ca(OH)2, a significant reduction in the median levels of endotoxins was found in comparison to CMP alone (from 1.041 to 0.094EU/mL) (p<0.05). Despite the type of treatment, the supplemental PDT was not effective against endotoxins (p>0.05). CONCLUSIONS: The photodynamic therapy optimized the disinfection of bacteria from root canals in one-visit but not for two visit treatment modality with the accomplishment of calcium hydroxide medication. Despite the type of treatment, the supplemental PDT was not effective against endotoxins.