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.

Influence of Apical Periodontitis on Stress Oxidative Parameters in Diabetic Rats

Introduction

In this study, we investigated if apical periodontitis (AP) associated with diabetes influenced the levels of endogenous antioxidants, the total antioxidant capacity (TAC), and the oxidant parameter in the serum of Wistar rats.

Immunoexpression of Interleukin 17 in Apical Periodontitis Lesions

Introduction

Interleukin (IL)-17 expression has been detected in apical periodontitis lesions, but its role in the disease process remains unclear. The present study compared the expression of IL-17 in periradicular cysts and granulomas and evaluated the association of this cytokine with clinical and radiographic findings.

Methods

Apical periodontitis lesions (18 cysts and 20 granulomas) were obtained from 38 patients subjected to periradicular surgery. Some clinical, radiographic, and cone-beam computed tomographic features were recorded. Silanized slides containing paraffin sections were used for the immunohistochemical reactions using anti–IL-17 antibody. Image analysis was performed using an optical microscope, and each sample was divided into 5 high-power fields, which were evaluated for the expression of IL-17 in the epithelium and connective tissues. Results were evaluated for correlations with the lesion size and the occurrence of symptoms and sinus tract.

Results

Expression of IL-17 was significantly higher in cysts than in granulomas (P = .02). Among the periradicular cysts, a thin epithelium showed significantly increased labeling for IL-17 when compared with a hyperplastic epithelium (P = .003). IL-17 expression was usually associated with focal accumulations of polymorphonuclear leukocytes. No association of IL-17 expression with symptoms, sinus tract, or lesion size was observed (P > .05).

Conclusions

The present study reinforces the notion that IL-17 may take part in the pathogenesis of apical periodontitis lesions. A role in the exacerbation of chronic inflammation and cyst formation is suspected. Further studies are required to shed light on the specific functions of IL-17 in periradicular inflammatory processes.     

Overlapping Protective and Destructive Regulatory Pathways in Apical Periodontitis

Introduction

Protective and destructive immunoreactions take place simultaneously in apical periodontitis. However, the same reactions defending the periapical area from infection-derived damage may also result in host tissue injury.

Methods

The inflammatory reaction of the periapical tissues is self-limited. Regeneration of the injured tooth-supporting structures may follow elimination of the causative microbial irritation.

Results

Recent experimental and clinical observations have identified important interplay between positive and negative regulatory pathways. A network of stimulatory and inhibitory feedback loops may influence the intensity of the defense and inflammatory responses and the balance between bone resorption and regeneration, resulting in lesion expansion or healing of apical periodontitis.

Conclusions

We critically discuss research data on regulatory mechanisms that control the activity of host effector cells and signaling molecules during interactions with pathogenic microbes.     

Immunoexpression of Interleukin 17, 6, and 1 Beta in Primary Chronic Apical Periodontitis in Smokers and Nonsmokers

IntroductionThe purpose of this study was to compare the immunoexpression of biomarkers interleukin (IL)-17, IL-6, and IL-1β in primary chronic apical periodontitis in smokers and nonsmokers.MethodsTeeth with primary chronic apical periodontitis indicated for extraction in 16 cigarette smokers and 16 nonsmokers were selected. Silanized sections of tissue were used for immunohistochemical analysis after being stained with hematoxylin-eosin for histopathologic categorization. Subsequently, the images were analyzed with an optical microscope, and each slide was subdivided into 5 high-magnification fields, with scores (0–2) being assigned according to the amount of staining for each antibody.ResultsThe qualitative analysis of IL-17 cytokine expression showed no focal expression in 5.8%, weak to moderate expression in 17.6%, and strong expression in 76.4% of the smokers and no focal expression in 78.5% and weak to moderate expression in 21.4% of the nonsmokers. IL-6 expression was negative to focal in 13.3%, weak to moderate in 53.3%, and strong in 33.3% of the smokers and negative to focal in 33.3%, weak to moderate in 25%, and strong in 41.6% of the nonsmokers. IL-1β expression was weak to moderate in 87.5% and negative to focal expression in 12.5% of the smokers and negative to focal expression in 100% of the nonsmokers. Quantitative evaluation of the data using the Mann-Whitney U test showed a significant difference in the immunoexpression of IL-17 (P < .0001) and IL-1β (P < .0001) and no significant difference in the immunoexpression of IL-6 (P = .46) between the 2 groups (P < .05).ConclusionsThe cytokines IL-17 and IL-1β were more highly expressed in smokers than nonsmokers, whereas IL-6 expression was similar in the 2 groups.     

Endodontic Microbial Communities in Apical Periodontitis

IntroductionApical periodontitis (AP) represents an inflammatory condition of peri-radicular tissues due to invasion and colonization of bacteria in the root canals. Primary apical periodontitis (PAP) is associated with untreated necrotic root canal and can be efficiently treated with endodontic treatment to remove bacteria. Persistent/secondary apical periodontitis (SAP) is a perpetual periapical lesion due to unsuccessfully treated root canals after an initial apparent healing of the tooth. The aim of the study was evaluating the microbial communities associated with root canals using Nanopore sequencing.MethodsSeventeen samples from the root canals of 15 patients with AP were Polymerase Chain Reaction-amplified for 16s ribosomal DNA gene and sequenced. Information regarding the presence or absence of AP symptoms, PAP and SAP, and periapical index of patients were recorded.ResultsFirmicutes, Bacteroidetes, and Actinobacteria were the most abundant phyla detected and Phocaeicola, Pseudomonas, Rothia, and Prevotella were the most prominent genera. In samples of patients with AP symptoms, the most frequent detected genera were Cutibacterium, Lactobacillus, Pseudomonas, Dialister, Prevotella, and Staphylococcus. In PAP samples, the most represented genera were Cutibacterium, Lactobacillus, Pseudomonas, and Prevotella, whilst in SAP cases were Cutibacterium, Prevotella, Atopobium, Capnocytophaga, Fusobacterium, Pseudomonas, Solobacterium, and Streptococcus.ConclusionsThe results provide additional information on the microbiota of root-canals. These data evidence the complexity of the microbiota and the relationship with many clinical and endodontic conditions. Future studies must evaluate these conditions and identify their role in inducing bone damage and local and systemic disease, aiming to better elucidate the relationship between microbes and endodontic pathologies.     

An Overview on Biologic Medications and Their Possible Role in Apical Periodontitis

Introduction

Apical periodontitis (AP) is the expression of a deficient balance between infection and the host immune response.

Methods

If reducing the bacterial load from the root canal and preventing its reinfection may lead to clinical success, then the integrity of the nonspecific immune system has a relevant influence on the outcome of endodontic treatment.

Results

Compromised immune systems and/or genetic alterations of the host's response may as well play an important role on the development, progression, and healing of AP. Thus, immunomodulatory drugs might have the potential to influence both the severity of AP and the outcome of endodontic treatment. Biologic medications are a new class of drugs of monoclonal antibodies or fusion proteins that include fragments of a peculiar cytokine receptor. Specific inflammatory molecules or cells, such as tumor necrosis factor, interleukins, and T or B cells, are the selective targets of these drugs. They modulate the altered immune response and perform an important role in the short-term treatment of chronic inflammatory diseases such as rheumatoid arthritis, refractory Crohn disease, or ulcerative colitis. Despite the clinical positive outcomes and their widespread use, the consequences of administering biologic medications on the development of the dental diseases have not been adequately investigated.

Conclusions

The aim of this review was to give an overview of biologic medications, their composition, their mechanisms of action, and their possible implications on endodontic and other dental diseases.     

Ovariectomy Exacerbates Apical Periodontitis in Rats with an Increase in Expression of Proinflammatory Cytokines and Matrix Metalloproteinases

Introduction

The aim of this study was to evaluate the gene expression of proinflammatory cytokines, matrix metalloproteinases (MMPs), and cathepsin K in apical periodontitis (AP) and the volume of lesions in ovariectomized and sham-operated rats.

Prevalence of Ciliated Epithelium in Apical Periodontitis Lesions

Introduction

This article reports on the morphologic features and the frequency of ciliated epithelium in apical cysts and discusses its origin.

Methods

The study material consisted of 167 human apical periodontitis lesions obtained consecutively from patients presenting for treatment during a period of 12 years in a dental practice operated by one of the authors. All of the lesions were obtained still attached to the root apices of teeth with untreated (93 lesions) or treated canals (74 lesions). The former were obtained by extraction and the latter by extraction or apical surgery. Specimens were processed for histopathologic and histobacteriologic analyses. Lesions were classified, and the type of epithelium, if present, was recorded.

Results

Of the lesions analyzed, 49 (29%) were diagnosed as cysts. Of these, 26 (53%) were found in untreated teeth, and 23 (47%) related to root canal–treated teeth. Ciliated columnar epithelium was observed partially or completely lining the cyst wall in 4 cysts, and all of them occurred in untreated maxillary molars. Three of these lesions were categorized as pocket cysts, and the other was a true cyst.

Conclusions

Ciliated columnar epithelium-lined cysts corresponded to approximately 2% of the apical periodontitis lesions and 8% of the cysts of endodontic origin in the population studied. This epithelium is highly likely to have a sinus origin in the majority of cases. However, the possibility of prosoplasia or upgraded differentiation into ciliated epithelium from the typical cystic lining squamous epithelium may also be considered.     

Genetic Polymorphisms in RANK and RANKL are Associated with Persistent Apical Periodontitis

Introduction

The outcome of root canal treatment has been reported as intimately related to the host response. Genetic polymorphisms might be associated with apical periodontitis repair. The aim of this study was to evaluate the association between receptor activator of nuclear factor kappa B (RANK), receptor activator of nuclear factor kappa B ligand (RANKL), and osteoprotegerin (OPG) genetic polymorphisms with persistent apical periodontitis (PAP) in Brazilian subjects.

Stem Cell Marker Expression in Persistent Apical Periodontitis

Introduction

This study evaluated the expression of CD90 (mesenchymal stem cell) and Sox2 (progenitor stem cell) markers in persistent apical periodontitis (PAP) (n = 16) and primary periapical lesions (PPLs) (n = 10).

Effects of Melatonin on Oxidative Stress Index and Alveolar Bone Loss in Diabetic Rats With Periodontitis

Background: The aim of this study is to evaluate the effects of systemic melatonin treatment on serum oxidative stress index (OSI) and alveolar bone loss (ABL) in rats with diabetes mellitus (DM) and periodontitis. Methods: Seventy Sprague Dawley rats were divided into control, experimentally induced periodontitis (EP), DM, EP‐DM, EP and melatonin treatment (EP‐MEL), DM and melatonin treatment (DMMEL), and EP‐DM‐MEL groups. DM was induced by alloxan, after which periodontitis was induced by ligature for 4 weeks. After removal of the ligature, the rats in the melatonin groups (EP‐MEL, DM‐MEL, and EP‐DM‐MEL) were treated with a single dose of melatonin (10 mg/body weight) every day for 14 consecutive days. At the end of the study, all of the rats were euthanized, and intracardiac blood samples and mandible tissues were obtained for biochemical and histologic analyses. Serum levels of total oxidant status/total antioxidant status and OSI were measured. In addition, neutrophil and osteoclast densities and myeloperoxidase activities were determined in gingival tissue homogenates, and ABL was evaluated with histometric measurements. Results: Melatonin treatment significantly reduced fasting plasma glucose levels in the rats with DM. In addition, reduced OSI and ABL levels were detected in the EP‐MEL and DM‐MEL groups; the reductions in the EP‐DM‐MEL group were found to be more prominent. Melatonin also significantly decreased the increased myeloperoxidase activities and osteoclast and neutrophil densities in the EP, DM, and EP‐DM groups. Conclusion: It is revealed in this experimental study that melatonin significantly inhibited hyperglycemia‐induced oxidative stress and ABL through antiDM and antioxidant effects in rats with DM and periodontitis.     

Periapical and endodontic status of type 2 diabetic patients in Catalonia, Spain: a cross-sectional study

Introduction

The aim of this study was to investigate radiographically the prevalence of apical periodontitis (AP) and endodontic treatment in a sample of adult type II diabetic patients and control subjects.

Methods

In a cross-sectional study, the radiographic records of 50 adult patients reporting a history of well-controlled type 2 diabetes mellitus (DM) (study group) and 50 age- and sex-matched subjects who reported no history of DM (control group) were examined. Periapical status of all teeth was assessed using the periapical index score.

Results

The average number of teeth per patient in the diabetic and control groups was 21.9 and 24.6 teeth, respectively (P = .012). AP in one or more teeth was found in 37 diabetic patients (74%) and in 21 control subjects (42%) (odds ratio = 3.9, P = .002). One or more root-filled teeth were found in 35 (70%) and 25 (50%) of diabetic and control subjects, respectively (odds ratio = 2.3, P = .043). Among diabetic patients with root-filled teeth, 16 (46%) had AP affecting at least one treated tooth. Among controls with root-filled teeth, 6 (24%) had AP affecting at least one treated tooth (P > .05). Adjusting for teeth number, multivariate logistic regression analysis showed that periapical status (odds ratio = 3.3, P = .0071) and the number of root-filled teeth (odds ratio = 1.7; P = .0035) were significantly associated with diabetic status.

Conclusions

The results showed that in adult patients, type 2 DM is significantly associated with an increased prevalence of AP and endodontic treatment.     

Accuracy of Cone-beam Computed Tomography and Periapical Radiography in Apical Periodontitis Diagnosis

Introduction

This study aimed to investigate the correlation and the agreement between periapical radiography (PR) and cone-beam computed tomography (CBCT) correlating to histologic findings in the diagnosis of apical periodontitis (AP).

Methods

One hundred thirty-four premolar root canals from 10 dogs were treated after AP induction. Four months later, the animals were killed, and standard digital PRs were obtained. The area of AP was measured by using ImageJ software. CBCT (i-CAT) images from each arch were obtained, and AP area and volume were measured by using Osiri-X software. The apical inflammatory infiltrate was evaluated under light microscopy. The correlation between imaging methods was evaluated by using the Pearson coefficient. The Bland-Altman method was used to assess the agreement between PR and CBCT data. The Spearman coefficient was used to correlate the imaging data and histologic findings.

Results

Despite a strong correlation between PR and CBCT areas, the agreement limits were very broad (95% limits of agreement, 0.19–1.08). PR only measured, on average, 63% of CBCT values. Although there was a strong correlation between PR area and CBCT volume, the Bland-Altman method suggests that the larger the CBCT volume, the more underestimated the PR value. When APs had a volume smaller than 6 mm³, the PR estimation of CBCT data was unpredictable. A positive correlation was found for PR area, CBCT area, CBCT volume, and histology data.

Conclusions

The diagnosis of AP based on PR data is clinically limited, and it should not be used for scientific investigations.     

MMP-7 and TIMP-1, New Targets in Predicting Poor Wound Healing in Apical Periodontitis

Introduction

Matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs) are strongly associated with tissue destruction because of inflammation. In this study, we investigated the expression of MMPs and TIMPs messenger RNA and protein levels in apical periodontitis lesions.

Methods

Tissue samples from patients presenting clinical signs of chronic apical abscess (CAA) or asymptomatic apical periodontitis (AAP) were collected postoperatively and used for gene expression analysis of MMP-2, -3, -7, -9, -14, -16, and -25; TIMP-1; and TIMP-2 in real-time polymerase chain reaction. Immunohistochemistry was also performed to detect the expression of MMP-7 and TIMP-1 proteins. Lastly, U-937 cells were induced to terminal differentiation into macrophages, infected with purified Escherichia coli lipopolysaccharide, and assessed for the expression of MMP-7 and TIMP-1 using immunocytochemistry and confocal microscopy.

Results

Significantly higher messenger RNA levels were found for all genes in AAP and CAA samples when compared with healthy control samples (P < .001). AAP cases exhibited significantly higher TIMP-1 when compared with CAA cases, whereas CAA cases showed higher MMP-2, MMP-7, and MMP-9 messenger RNA levels (P < .05). We also detected positive the expression of MMP-7 and TIMP-1 proteins in the tissue samples. The expression of both MMP-7 and TIMP-1 were increased in lipopolysaccharide-stimulated cells compared with nonstimulated cells and appear to colocalize in the Golgi apparatus.

Conclusions

MMPs appear to have an influential role in CAA cases in which ongoing tissue destruction is observed. TIMPs are preferentially associated with AAP, perhaps as a subsequent defense mechanism against excessive destruction. Taken together, our findings implicate MMP and TIMP molecules in the dynamics of inflammatory periapical lesion development.     

Elevated Cytokine Levels in Gingival Crevicular Fluid of Teeth with Apical Periodontitis

IntroductionBiomarkers assayed from gingival crevicular fluid (GCF) are a potential tool for endodontic diagnosis and for monitoring treatment response. This cross-sectional study measured cytokines in GCF from teeth with apical periodontitis and evaluated their relationship with preoperative pain and other clinical findings.MethodsParticipants presenting for root-end resection surgery due to apical periodontitis diagnosis (n = 56) underwent standardized clinical testing and completed preoperative questionnaires. GCF from diseased and control teeth were collected, processed, and analyzed. Mann-Whitney U and Wilcoxon tests were used to examine the cytokine levels in diseased compared to healthy control teeth. We also assessed the relationship of cytokine levels with clinical findings.ResultsInterleukins (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon-γ, and tumor necrosis factor-⍺ (TNF-⍺) were detected in GCF. TNF-⍺ levels were significantly higher in GCF collected from diseased versus control teeth (P = .02) and increased IL-1β levels in diseased teeth were detected (P = .06). Lower IL-10 levels were observed in teeth with a sinus tract and/or swelling compared to teeth without a sinus tract and/or swelling (P = .08). Cytokine levels did not clearly relate to the presence of pain.ConclusionsElevated levels of proinflammatory cytokines, including TNF-⍺ and IL1- β, were detected in GCF from diseased teeth compared to the healthy controls. Additional studies are needed to further investigate the utility of these biomarkers for objectively evaluating periradicular pathology.