The Effect of Lasers on the Healing of Periapical Lesion: A Systematic Review.

Introduction: Endodontic treatment of teeth with periapical lesions presents more clinical difficulty. Various lasers in several methods are used in endodontics, and most of them are utilized as an adjunctive protocol in order to reduce the bacterial load of the root canal system. Improved disinfection plays a crucial role in enhanced and accelerated healing of periapical lesions. This review aims to summarize studies assessing the effect of lasers on periapical lesion healing. Methods: PubMed/MEDLINE, Scopus, Embase, and Web of Science (ISI) online databases were searched, with no publication year or status restriction, for relevant articles on April 2023. Clinical studies evaluating the effect of laser application on the periapical lesion of patients using radiographic assessment were considered eligible for inclusion. Results: Eight studies were included after carefully screening the obtained articles, first by their title and abstract and then by their full texts. Diode (4), Er, Cr: YSGG (3), and Nd: YAG (1) lasers were used with output powers that varied from 0.75 to 2 watts. Photodynamic therapy was employed in two studies, and in other studies, the root canal system was directly irradiated. Irradiation of the root canal system was adjunctive to standard preparation in all studies. The healing of the teeth treated with lasers was not inferior to those conventionally treated. In all of the included studies, laser application outperformed the standard cleaning and shaping protocol; however, this improved or faster healing was not statistically significant in most studies. Conclusion: Lasers might expedite and improve the healing process of periapical lesions. Since lasers enhance the quality of cleaning of the root canal system, it is hard to point out the exact mechanism of it. Further investigations are needed to realize the effectiveness of this treatment modality and to discover the underlying biological concepts.

Human Periapical Odontogenic Granulomas: Aspects of Microvessel Density (MVD), Heterogeneity of Blood Vessels and Mast Cells Density (MCD).

Periapical odontogenic granulomas are among the most encountered pathology that involve the alveolar bone, with severe consequences such as bone resorption, the presence of inflammatory infiltrate and the formation of abnormal vascularization. The present study aimed to quantify the existence of the microvessel density (MVD), mast cell density (MCD) and heterogeneity of the encountered blood vessels. A total of 37 patients diagnosed with odontogenic periapical granulomas were included, and the gender distribution, age and localization of the pathological lesions was assessed. After the surgical removal of the periapical odontogenic granuloma, the collected tissue was fixed in 10% buffered formalin. Primary processing, morphological analysis and immunohistochemical staining was performed in order to characterize the altered tissue. The results outlined the presence of a high number of mast cells, especially in the area of the inflamed tissue; the high heterogeneity of the blood vessels; and increased MVD with positive CD34. The conclusions of the study focus on the key role of the mast cells and their implication in the initiation and development of the angiogenesis process, triggering the inflammatory response of the host. Nevertheless, periapical odontogenic granulomas develop as an inflammatory response to the interaction between the host's immune system and microbial invasion.

Interleukin 17 expression in periapical lesions from elderly patients.

OBJECTIVE: To compare the expression of IL-17 in periapical lesions (cysts and granulomas) among elderly individuals and adults. We selected 20 periapical lesions of the elderly (12 granulomas and eight cysts) and 20 periapical lesions of adults (12 granulomas and eight cysts). MATERIALS AND METHODS: Immunohistochemistry was performed using a specific antibody for IL-17. The slides were subdivided into five high magnification fields and then the images were observed through an optical microscope. According to the number of positive markings for the antibody, grades were given, ranging from 0 to 2. RESULTS: The results demonstrate that there was no statistical difference when comparing the expression of IL-17 between cysts and granulomas of both groups (study group: cysts 0.7 ± 0.21 × granulomas 0.96 ± 0.58, p = .61; control group: cysts 0.37 ± 0.16 × granulomas 0.31 ± 0.23, p = .27). The comparison between adult (control group) and elderly patients (study group) showed a statistical difference both in cysts (study group: 0.7 ± 0.21 × control group: 0.37 ± 0.16, p = .007) and in granulomas (study group: 0.96 ± 0.58 × control group: 0.31 ± 0.23, p = .0009), in which elderly patients had a higher expression of interleukin 17, in relation to adult patients. CONCLUSION: We concluded that elderly patients have a higher expression of IL-17 in both cysts and granulomas, when compared to adult patients.

Frequency and Types of Periapical Radiographic Lesions Associated With Pulpitis in a Tertiary Care Hospital.

Objective This cross-sectional study aimed to determine the frequency and types of periapical radiographic lesions (PARLs) associated with pulpitis in patients visiting a tertiary care hospital. Methodology A sample of patients diagnosed with pulpitis, aged 18 years or older, was recruited following a convenient sampling technique. Clinical examinations were conducted to confirm the diagnosis, and radiographic evaluations, including periapical (PA), occlusal, orthopantomogram (OPG), and cone beam computed tomography (CBCT) radiographs were obtained. The radiographs were evaluated for the presence of PA lesions, and the type, size, and location of the lesions were documented. Data were analyzed using IBM SPSS Statistics for Windows, Version 25.0 (IBM Corp., Armonk, NY, USA). Results A total of 120 patients (equal gender ratio) with a mean age of 32.6 ± 6.39 years participated in the study. PA views were the most frequently performed radiographic view (86.7%), followed by occlusal views (8.3%). The most prevalent radiographic lesion was the widening of the periodontal ligament (PDL) space (34.2%), followed by PA granuloma (17.5%) and PA cyst (10.8%). The most frequently encountered diagnosis was pulpitis (51.7%), followed by irreversible pulpitis with apical periodontitis (25.8%). Education level, swelling, pus discharge, medicine history, and tooth wear showed statistically significant associations (P ≤ 0.05) with the variables under investigation. Conclusions The most common lesions observed were widening of the PDL space, PA granuloma, and PA cyst. The findings contribute to the local epidemiological and clinical data, enriching the existing database. Understanding the prevalence and characteristics of PA lesions associated with pulpitis can aid in accurate diagnosis and treatment planning for patients with pulpal pathologies.

Periapical foreign body findings - histological and radiological comparison.

OBJECTIVE: This study aimed to clarify the perceptibility of periapical foreign materials in imaging compared with histopathology. We hypothesized that dentoalveolar imaging is sufficient to detect periapical foreign bodies. MATERIAL AND METHODS: Radiological and histopathological records of patients diagnosed with periapical granuloma or radicular cyst from 2000 to 2013 were evaluated retrospectively. Patients with histologically verified foreign bodies were included in the study and their pathological samples and radiological images were reviewed. The outcome variable was radiologically detectable foreign material. The predictor variables were histopathological diagnosis, type of inflammation, type and number of foreign bodies, imaging modality, and site of foreign material. RESULTS: Compared to the histopathological diagnosis of foreign bodies as the gold standard, the level of radiologic detectability was mild. Histologically verified foreign material could be detected by imaging in 32/59 (53.5%) patients. Histological diagnosis, type of inflammation, type or number of foreign bodies, imaging modality or site of foreign material had no association with radiological detectability (p > 0.05). CONCLUSIONS: According to our results, histopathology is a more accurate diagnostic tool than radiology in periapical foreign bodies or foreign body reactions. Clinicians should keep in mind the limitations of imaging when setting the diagnosis and planning treatment.

Immunohistochemical evaluation of cyclooxygenase-2 and mast cell density in periapical lesions.

AIM: Periapical granuloma (PG) and cyst (PC) are formed as a protective response consequent to pulpal infection leaching through the apical foramen and lateral canals. Various inflammatory mediators like mast cells and cyclooxygenase (COX)-2 are involved in this intricate process. This pilot study aimed to evaluate and compare the immunoexpression of tryptase and COX-2 in periapical granuloma and periapical cyst, and also correlate them with intensity of inflammatory infiltrate and thickness of cystic epithelial lining. METHODOLOGY: An observational and cross-sectional study was conducted on paraffin-embedded tissue sections of 50 PGs and 50 PCs submitted for morphological and immunohistochemical analysis using anti-tryptase and anti-COX-2 antibodies. The mean number of mast cells (total, granulated and degranulated), mean COX-2 expression and inflammatory score was calculated. The data obtained were analysed using Mann Whitney U, Student's T, Chi-square and Spearman correlation test (p < .05). RESULTS: The inflammatory score, total mast cells and COX-2 expression were similar in PGs and PCs (p = .352, .339 and .352) however, the degranulated mast cells were highly significant in PC while granulated mast cells were highly significant in PG respectively (p < .001 in both). Although a non-significant correlation existed between COX-2 and total mast cells in both groups but, total mast cells were significantly correlated with epithelial thickness in PC (p = .029). CONCLUSIONS: Mast cells and cyclooxygenase-2 proved to be independent inflammatory markers in periapical lesions. Further studies should be planned on mast cell and COX-2 inhibitors as treatment modalities of periapical lesions.

Hypercitrullination and anti-citrullinated protein antibodies in chronic apical periodontitis, a laboratory investigation. Does autoimmunity contribute to the pathogenesis?

AIM: The presence of Gram-negative anaerobic bacteria, in particular, Porphyromonas gingivalis (P. gingivalis) in periapical granulomas predicts the generation of citrullinated proteins in the lesion. Citrullination of proteins may lead to the formation of anti-citrullinated autoantibodies (ACPA-s) initiating the formation of an autoimmune loop which may contribute to the perpetuation of inflammatory reactions and tissue damage in chronic apical periodontitis. The objective of this study was to demonstrate the formation of citrullinated proteins in chronic apical periodontitis and whether they can act as autoantigens. METHODOLOGY: Twenty-five periapical granulomas (n = 25) were investigated in the study. Healthy periodontal tissue samples served as normal control tissue (n = 6). The peptidyl-citrulline level was determined with the dot blot method. ACPA levels were analysed using anti-citrullinated cyclic peptide (anti-CCP) EDIA kit. Differences between periapical granuloma and control samples were assessed using Mann-Whitney U tests. p Values <.05 were considered as statistically significant. RESULTS: Protein concentrations, peptidyl-citrulline levels and anti-CCP ratios were compared between periapical granuloma and healthy control groups. Multiple linear regression analysis revealed significant (p = .042) hypercitrullination in periapical granuloma samples. Moreover, there was a significant difference in the ACPA ratios between periapical granuloma (2.03 ± 0.30) and healthy control (0.63 ± 0.17) groups (p = .01). Seventeen of 25 periapical granuloma samples (17/25; 68%), whereas one out of six control samples (1/6; 17%) were shown to be positive for the presence of ACPA. CONCLUSIONS: This is the first study detecting the presence of citrullinated peptides and APCA in periapical granuloma, suggesting the contribution of autoimmune reactions in the pathogenesis and perpetuation of chronic apical periodontitis.

The Potential Immunomodulatory Roles of Semaphorin 4D in Human Periapical Lesions.

INTRODUCTION: Semaphorin 4D (SEMA4D) is an important immunoregulator in the development of inflammatory diseases. Currently, the role of SEMA4D in human apical periodontitis remains unclear. This study aims to investigate the expression of SEMA4D and its potential immunomodulatory roles in apical periodontitis. METHODS: A total of 31 periapical tissues and 6 healthy gingival tissues were used in this experiment. Hematoxylin-eosin staining, immunohistochemical staining, and multiplex immunofluorescence staining were performed for histologic examination and immunochemical analysis. For data processing, the number of SEMA4D+, CD4+, CD8+, and CD20+ cells was analyzed by QuPath. In addition, the colocalization of SEMA4D with CD4, CD8, and CD20 was detected. RESULTS: Radicular cysts (RCs) (n = 18) and periapical granulomas (PGs) (n = 13) were identified by histologic evaluation. The number of SEMA4D+ cells in PGs was significantly greater than that in RCs (P < .05). T-cell and B-cell infiltration did not differ significantly between RCs and PGs. An increased number of CD20+ cells was observed in both types of apical periodontitis compared to CD8+ cells and CD4+ cells. Additionally, the presence of SEMA4D/CD4 and SEMA4D/CD20 double-positive cells was also markedly higher in PGs than in RCs. CONCLUSION: The expression of SEMA4D and related immune cells showed different characteristics between RCs and PGs. The disparate expression patterns indicated the possible different pathologic states of the 2 types of periapical lesions. This study provides a new perspective on the description of the comprehensive microenvironment of periapical lesions.

A Comparative Evaluation of Digital Radiography and Ultrasound Imaging to Detect Periapical Lesions in the Oral Cavity.

Purpose This study evaluates the efficacy of digital radiography and ultrasound (USG) for the distinction between periapical cysts and granulomas, determines the nature and extent of the periapical lesion, visualizes the lumen of the lesion, assesses its size, content, and vascularity. Material and Methods Thirty patients, ages 18 to 40, with well-defined periapical radiolucencies on maxillary or mandibular teeth, indicated for the extraction or periapical surgery, underwent digital radiography examination using the paralleling technique, followed by USG examination. A sonologist evaluated the lesions' size, echogenicity, and vascular content. The diagnosis was compared to histopathological examinations of tissues obtained through extraction or periapical surgery. Results The diagnostic value of USG compared to the histopathological diagnosis of the periapical cyst was greater than that of the radiographic diagnosis, with an ultrasonographic diagnostic sensitivity (SN) value of 60% and a radiographic diagnostic SN value of 40%, respectively. The diagnostic value of USG imaging against the histopathological diagnosis of periapical granuloma was slightly lower than that of digital radiography, with an SN value of 72.2% for USG and 83.33% for digital radiography. However, the specificity (SP) value and precision of USG imaging were superior to those of digital radiographic diagnosis. USG imaging and radiographic diagnosis had 58.33% and 50% SP values, respectively. In cases of periapical abscess, the diagnostic values of USG against histopathological diagnosis were lower than those of radiographic diagnosis, which had an SN value of 100%. Conclusion USG with color doppler is a more effective tool than digital radiography for diagnosing periapical lesions. The echo structure of the lesions and the presence of vascularity on USG with color doppler correlated with histopathology better than the radiological diagnosis.

Imunoexpressão de ING 4, VEGF e NF-κB em lesões periapicais inflamatórias / Immunoexpression of ING 4, VEGF and NF-κB in inflammatory periapical lesions

As lesões periapicais inflamatórias (LPIs) são condições patológicas decorrentes de infecções de origem odontogênica, principalmente representadas pelos granulomas periapicais (GPs) e cistos radiculares (CRs). Sua patogênese está associada a mecanismos imunológicos e angiogênicos. O presente estudo, do tipo retrospectivo, teve como objetivo analisar, de forma semiquantitativa, a expressão imuno-histoquímica de ING-4, VEGF e NF-κB em LPIs, e correlacionar o padrão de expressão dessas proteínas. A amostra consistiu de 26 GPs, 17 CRs e 19 cistos radiculares residuais (CRRs). Foram avaliados espessura epitelial e infiltrado inflamatório, e a associação desses achados com o padrão de expressão das proteínas ING-4, VEGF e NF-κB nas LPIs selecionadas. Para a realização da análise estatística, foram utilizados os testes de qui-quadrado, Kruskal-Wallis, Mann-Whitney e correlação de Spearman (p < 0,05). O infiltrado inflamatório exibiu maior intensidade no GP, seguido pelo CR, e por último, o CRR (p < 0,05). Apesar de não haver associação estatisticamente significativa ao associar a expressão de ING-4 nas células inflamatórias do tecido conjuntivo ou cápsula fibrosa entre os grupos de LPIs, o GP e CR evidenciaram, através da média de postos, maior expressão dessa proteína. Não foi evidenciada associação estatisticamente significativa de ING-4 com a intensidade do infiltrado inflamatório. A imunoexpressão de VEGF no núcleo das células inflamatórias do tecido conjuntivo ou cápsula fibrosa exibem associação significativa com as LPIs, que ocorre maior expressão dessa proteína nos cistos (p= 0,002). A maior expressão de NF-κB foi evidenciada nos casos de GPs, tanto a nível nuclear quanto citoplasmático das células inflamatórias (p = 0,005; p = 0,002). Não houve associação estatisticamente significativa quando comparada a expressão de NF-κB entre os cistos, mas a mediana da expressão dessa proteína foi maior para os CRs. Na cápsula fibrosa, a imunoexpressão nuclear e citoplasmática de NF-κB nas células inflamatórias foi superior nas lesões periapicais com intenso infiltrado inflamatório (p < 0,001). Portanto, sugere-se que ING-4, VEGF e NF-κB participam do desenvolvimento das LPIs, e apesar de ocorrer relação diretamente proporcional entre a expressão dessas proteínas, ING-4 não exerceu atividade reguladora na inflamação associada a essas lesões (AU).

Inflammatory periapical lesions (IPLs) are pathological conditions resulting from infections of odontogenic origin, being mainly represented by periapical granulomas (PGs) and radicular cysts (RCs). Its pathogenesis is associated with immunological and angiogenic mechanisms. This retrospective study, semi-quantitative and comparative aimed to analyze the immunohistochemical expression of ING-4, VEGF and NF-κB in IPLs, and to correlate the pattern of expression of these proteins. The sample consisted of 26 were PGs, 17 RCs and 19 residual radicular cysts (RRCs). Epithelial thickness and inflammatory infiltrate were evaluated, and the correlation of these findings with the expression pattern of ING-4, VEGF and NF-κB proteins in selected IPLs. To perform the statistical analysis, the chi-square, Kruskal-Wallis, Mann-Whitney and Spearman correlation tests were used (p < 0.05). The inflammatory infiltrate exhibited greater intensity in the PG, followed by the RC, and finally, the RRC (p < 0.05). Although there was no statistically significant association when associating the expression of ING-4 in inflammatory cells of the connective tissue or fibrous capsule the groups of IPLs, the PG and RC showed higher expression of this protein. There was no statistically significant association between ING-4 and the intensity of the inflammatory infiltrate. Immunoexpression of VEGF in the nucleus of inflammatory cells in the connective tissue or fibrous capsule shows a significant association with IPLs, in which there is greater expression of this protein occurring in cysts (p= 0,002). The highest expression of NF-κB was evidenced in cases of PGs, both at the nuclear and cytoplasmic level of inflammatory cells (p=0,005; p= 0,002). There was no statistically significant association when comparing the expression of NF-κB between the cysts, but the median expression of this protein was expression was higher for the RCs. In the fibrous capsule, nuclear and cytoplasmic NF-κB immunoexpression in inflammatory cells was higher in periapical lesions with intense inflammatory infiltrate (p<0.001). Therefore, it is suggested that ING-4, VEGF and NF-κB participate in the etiopathogenesis of IPLs, and that there is a directly proportional relationship between the expression of these proteins. ING-4 did not exert regulatory activity in the inflammation associated with these lesions (AU).

Prevalence of Nonendodontic Diagnoses in Periapical Biopsies: A 6-year Institutional Experience.

INTRODUCTION: The purpose of this study was to identify nonendodontic periapical lesions (NPLs) mimicking endodontic pathosis, which are most frequently encountered by clinicians. METHODS: A retrospective study was conducted on biopsies obtained from 2015-2020 at Texas A&M College of Dentistry's oral pathology laboratory. The online database was screened for cases submitted as suspected endodontic pathology using specific key words. Histologic diagnoses were collected to determine the prevalence of NPLs that were originally thought to be of endodontic origin. The frequency and percentage of endodontic pathology and NPLs were documented. RESULTS: Among 6704 biopsies clinically diagnosed as endodontic lesions, 190 (2.8%) were histopathologically diagnosed as NPLs. The most frequent NPLs were odontogenic keratocytes' (n = 70, 36.8%), cemento-osseous dysplasia (n = 27, 14.2%), and dentigerous cysts (n = 22, 11.6%). Of all NPLs, 3.7% were malignant neoplasms, with the most common diagnosis being squamous cell carcinoma. Of 6514 endodontic histologic diagnoses, the prevalence of periapical granulomas and cysts was 60.2% (n = 3924) and 39.1% (n = 2549), respectively. CONCLUSIONS: Although most endodontic submissions are likely to be histologically diagnosed as periapical granulomas or cysts, the clinician should be aware that a small portion of these lesions may be nonendodontic in origin and possibly neoplastic in nature. Histopathologic evaluation of biopsied specimens is critical to achieve a proper diagnosis to ensure the appropriate management of patients.

Evaluation of ultrasonography as a diagnostic tool in the management of periapical cysts and granulomas: A clinical study.

Purpose: The aim of this study was, firstly, to determine the concordance of ultrasonographic and histopathological diagnoses in patients in whom apical resection was already indicated. Secondly, this study aimed to determine whether lesions were periapical granulomas or cysts, and to compare them after root canal treatment using ultrasonography and periapical radiographs. Materials and Methods: In the first stage of the study, ultrasonographic and histopathologic diagnoses of 10 lesions were compared. Secondly, the periapical radiographs and ultrasonographic images of 44 lesions were measured. The presence of internal vascularity was determined by ultrasonographic color and power Doppler modes. Follow-up examinations of healing after root canal treatment were performed using ultrasonography and periapical radiographs, and these modalities were compared. Results: In the periapical granuloma and cyst groups, the measurement values decreased for all variables. There was no significant difference in the dimensional changes of lesions between the 2 groups, and ultrasonography and periapical radiographs were compatible. The pre-diagnoses were compared with histopathological diagnoses and were found to be compatible. Conclusion: The ultrasonographic color and power Doppler techniques could be an effective method for diagnosing periapical lesions as cysts or granulomas. After root canal treatment of granulomas and cysts, the dimensional shrinkage and healing patterns appear to be similar. Ultrasonography and periapical radiographs were consistent in terms of dimensional comparisons, and ultrasonography may be an alternative method for follow-up of the healing of periapical lesions.

Interplay of collagen and mast cells in periapical granulomas and periapical cysts: a comparative polarizing microscopic and immunohistochemical study.

Objectives: This pilot study aimed to establish the interrelationship between collagen and mast cells in periapical granulomas and periapical cysts. Materials and Methods: An observational cross-sectional study was conducted on the paraffin-embedded tissue sections of 68 specimens (34 periapical granulomas and 34 periapical cysts). The specimens were stained with picrosirius to observe collagen fiber birefringence and anti-tryptase antibody to evaluate the mast cell count immunohistochemically. The mean number and birefringence of collagen fibers, as well as the mean number of mast cells (total, granulated, and degranulated), and the mean inflammatory cell density were calculated. The data obtained were analyzed using the Kruskal Wallis test, Mann Whitney U test, and Spearman correlation test (p < 0.05). Results: The mean number of thick collagen fibers was higher in periapical cysts, while that of thin fibers was higher in granulomas (p = 0.00). Cysts emitted orange-yellow to red birefringence, whereas periapical granulomas had predominantly green fibers (p = 0.00). The mean inflammatory cell density was comparable in all groups (p = 0.129). The number of total, degranulated, and granulated mast cells exhibited significant results (p = 0.00) in both groups. Thick cyst fibers showed significant inverse correlations with inflammation and degranulated mast cells (p = 0.041, 0.04 respectively). Conclusions: Mast cells and inflammatory cells influenced the nature of collagen fiber formation and its birefringence. This finding may assist in the prediction of the nature, pathogenesis, and biological behavior of periapical lesions.

ALDH1 expression and potential clinical implications in chronic inflammatory periapical lesions

Abstract: Aldehyde dehydrogenase 1 (ALDH-1) is a marker of stem cells in a variety of diseases, but its role in individuals with chronic inflammatory periapical lesions remains unknown. The aim of this study was to investigate the presence of cells with a stem cell profile based on the immunoexpression of ALDH-1 in periapical granulomas (PGs) and radicular cysts (RCs). A total of 51 cases of periapical lesions (25 PGs and 26 RCs) were subjected to immunohistochemical study. The anti-ALDH-1 antibody was applied using the immunoperoxidase technique. An immunoexpression score (intensity vs. percentage of cells) was used, with the cases being classified as low expression (score: 0 to 4) and high expression (score: 6 to 9). The Chi-square test was used with a 5% level of significance. Immunoexpression of ALDH-1 was detected in all cases of PGs and RCs. In PG cases, the expression was diffuse in connective tissue cells, with most cases exhibiting high expression (n = 18; 69.2%), while in RC cases the expression revealed focal distribution in cells of the capsule and epithelial cells of the cystic lining, with most cases classified as low expression (n = 18; 72%). Significant differences in the expression scores of ALDH-1 were observed in PGs (p = 0.003). The variable expression of ALDH-1 suggests the presence of cells with stem cell profiles in PGs and RCs. These findings suggest that periapical tissues infiltrated by chronic inflammation can recruit important cells for the repair or evolution of periapical lesions.

Baseline MMP expression in periapical granuloma and its relationship with periapical wound healing after surgical endodontic treatment.

BACKGROUND: Matrix metalloproteinases (MMPs) catalyzes the degradation of the extracellular matrix components and have a major role in many physiological processes including wound healing. In the current study, we examined the correlation of baseline MMPs 1, 2, 7, and 9 expressions with periapical wound healing after surgical endodontic treatment. METHODS: 27 patients aged between 15 and 57 years presenting with chronic apical periodontitis or chronic apical abscess of an anterior tooth with previously attempted or failed root canal treatment were included in this study. During surgical endodontic treatment, tissue from the periapical lesion sample was collected and used for gross histopathological analysis as well as mRNA expression analysis of MMPs 1, 2, 7, and 9. Patients were recalled for follow-up after 6  months to evaluate the healing status both clinically and radiographically and healing was correlated with baseline MMP expression. RESULTS: Out of 27 patients, healing was observed in 15 patients at the end of 6 months, and in 21 patients after 12 months.. Six patients showed no healing even after 12 months. Analysis of baseline MMP 1, 2, 7, and 9 expression levels with healing status showed the mean relative expression of MMP2 and MMP9 to be considerably increased in the non-healing group as compared to the healing group. CONCLUSION: Overexpression of MMP2 and MMP9 may be considered as a potential prognostic biomarker for periapical wound healing after surgical endodontic treatment. However, further studies are desirable to establish its precise relationship with periapical wound healing.

Comparative Metabolomics Reveals the Microenvironment of Common T-Helper Cells and Differential Immune Cells Linked to Unique Periapical Lesions.

Periapical abscesses, radicular cysts, and periapical granulomas are the most frequently identified pathological lesions in the alveolar bone. While little is known about the initiation and progression of these conditions, the metabolic environment and the related immunological behaviors were examined for the first time to model the development of each pathological condition. Metabolites were extracted from each lesion and profiled using gas chromatography-mass spectrometry in comparison with healthy pulp tissue. The metabolites were clustered and linked to their related immune cell fractions. Clusters I and J in the periapical abscess upregulated the expression of MMP-9, IL-8, CYP4F3, and VEGF, while clusters L and M were related to lipophagy and apoptosis in radicular cyst, and cluster P in periapical granuloma, which contains L-(+)-lactic acid and ethylene glycol, was related to granuloma formation. Oleic acid, 17-octadecynoic acid, 1-nonadecene, and L-(+)-lactic acid were significantly the highest unique metabolites in healthy pulp tissue, periapical abscess, radicular cyst, and periapical granuloma, respectively. The correlated enriched metabolic pathways were identified, and the related active genes were predicted. Glutamatergic synapse (16-20),-hydroxyeicosatetraenoic acids, lipophagy, and retinoid X receptor coupled with vitamin D receptor were the most significantly enriched pathways in healthy control, abscess, cyst, and granuloma, respectively. Compared with the healthy control, significant upregulation in the gene expression of CYP4F3, VEGF, IL-8, TLR2 (P < 0.0001), and MMP-9 (P < 0.001) was found in the abscesses. While IL-12A was significantly upregulated in cysts (P < 0.01), IL-17A represents the highest significantly upregulated gene in granulomas (P < 0.0001). From the predicted active genes, CIBERSORT suggested the presence of natural killer cells, dendritic cells, pro-inflammatory M1 macrophages, and anti-inflammatory M2 macrophages in different proportions. In addition, the single nucleotide polymorphisms related to IL-10, IL-12A, and IL-17D genes were shown to be associated with periapical lesions and other oral lesions. Collectively, the unique metabolism and related immune response shape up an environment that initiates and maintains the existence and progression of these oral lesions, suggesting an important role in diagnosis and effective targeted therapy.

Association between Cone-Beam Computed Tomography and Histological and Immunohistochemical Features in Periapical Lesions Correlated with Thickened Maxillary Sinus Mucosa.

Background and Objectives: Odontogenic sinusitis is a frequently underestimated pathology with fewer symptoms in patients with periapical lesions, periodontal disease, or iatrogenic foreign bodies in the maxillary sinus. The aim of our study was to determine the correlation between maxillary sinusitis and periapical lesions using cone-beam computed tomography (CBCT) imaging and histological and immunohistochemical investigations. Materials and Methods: A total of 1450 initial patients diagnosed with maxillary sinusitis in the Ear-Nose-Throat (ENT) Department, University of Medicine and Pharmacy "Grigore T. Popa" Iasi, Romania, were treated with anti-inflammatory drugs. Of these, 629 still had unresolved symptomatology and were later referred to the Dental Medicine departments for further investigations. Only 50 subjects with periapical lesions in the premolar/molar maxillary area were included in the present study. All the periapical lesions were observed on CBCT and classified using the Periapical Status Index (PSI) and the mean maxillary sinus mucosa thicknesses (MSMT). The enrolled patients underwent surgical procedures with the excision of periapical lesions. The excised samples were submitted to the histological and immunohistochemical investigations. Results: The 50 patients presented periapical lesions of their maxillary teeth in 328 dental units. There was a higher prevalence of periapical lesions in men than in women (chi-square test). We observed a significant difference between the mean MSMT of individuals with periapical lesions compared to those without (p < 0.01). Mean MSMT was 1.23 mm for teeth without periapical lesions and 3.95 mm for teeth with periapical lesions. The histopathological study identified 50% cases with periapical granulomas, 10% cases with periapical granulomas with cystic potential, and 40% cases as periapical cysts. Immunohistochemical stainings showed that CD4+ helper and CD8+ cytotoxic T lymphocytes, along with CD20+ B lymphocytes and CD68+ macrophages, were diffusely distributed in all periapical cysts and in some periapical granulomas, but CD79α+ plasma cells characterized especially periapical granulomas. Conclusions: The current study observed a significant correlation between CBCT maxillary mucosa thickness and type of periapical lesion. Chronic inflammatory lympho-histiocytic infiltrate predominates in periapical lesions, supporting the idea that lesion progression is determined by a humoral-type (CD20+ and CD79α+ B lymphocytes) but also by a cellular-type (CD4+ and CD8+ T lymphocyte population) immune mechanism.

Detección y cuantificación de células plasmáticas (plasmocitos) en granulomas periapicales inducidos experimentalmente en ratas / Detection and quantification of plasma cells in experimentally induced rat periapical granulomas

Objetivo: En los granulomas periapicales, los plasmocitos (PL) participan activamente mediante la liberación de inmunoglobulinas. El propósito de este ensayo fue identificar y contar el número de PL en diferentes períodos de tiempo en lesiones periapicales experimentales en ratas. Materiales y métodos: Mediante la exposición al medio oral de la pulpa de los primeros molares inferiores izquierdos, se indujeron granulomas periapicales en ratas a las que previamente se les suministró anestesia. La pulpa de los primeros molares inferiores derechos no fue expuesta, y estos dientes se utilizaron como control. Los animales fueron eutanasiados a los 10, 30 y 60 días de la exposición. Los maxilares inferiores fueron removidos, y los primeros molares, junto con los tejidos circundantes, se procesaron para su estudio histológico. Se obtuvieron secciones semiseriadas, posteriormente coloreadas con verde de metilo-pironina (VMP). Cada tres secciones, las tres siguientes fueron coloreadas con hematoxilina y eosina (H-E). Los controles también fueron coloreados con H-E. Resultados: Todos los especímenes experimentales coloreados con H-E revelaron la presencia de granulomas periapicales. Luego de la exposición pulpar, el número de PL que reaccionó positivamente al VMP se incrementó de manera progresiva desde el día 10 hasta los días 30 y 60. A pesar de que a los 60 días el número de PL fue ligeramente menor que a los 30 días, no hubo diferencias estadísticamente significativas entre estos dos períodos. Los especímenes del grupo control coloreados con H-E mostraron que los tejidos periapicales se encontraban dentro de los parámetros normales en todos los períodos de observación. Conclusiones: Los resultados de este estudio revelaron que el número de plasmocitos VMP positivos se incrementa progresivamente en función del tiempo transcurrido pero se estabiliza al finalizar el experimento. También sugieren que el empleo de la coloración de VMP es un procedimiento adecuado para la identificación y la cuantificación de plasmocitos en los granulomas periapicales inducidos experimentalmente en ratas (AU)

Aim: Plasma cells (PL) release immunoglobulin in periapical lesions. The purpose of this assay was to identify and count the number of plasmocytes observed in periapical lesions in rats. Materials and methods: By exposing the pulp of the lower left first molars to the oral environment, periapical granulomas were induced in rats previously anesthetized. The pulp of right mandibular first molars was not exposed and these teeth were used as negative controls. The animals were euthanized at 10, 30 and 60 days after pup exposure. The mandibles were removed and specimens of the molar teeth along with the surrounding tissues were prepared for histology. Semi serial sections of the left first molar were stained with methyl green pyronine (MGP). Every three sections, the following three sections were stained with hematoxilyn and eosin (H-E). Negative control samples were stained with H-E. Results: All the H-E stained experimental samples revealed the presence of periapical granulomas. After pulp exposure, the number of PL increased from day 10 to 30 and 60. In the 60-day samples the number of PL was slightly less than that of the 30-day samples, with no statistically significant difference. The H-E stained control samples showed normal periapical tissues in all observation periods. Conclusions: The results of this study revealed that the number of VMP positive PL, increased progressively with time but it was stabilized at the end of the experiment. In addition, the results suggest that the use of VMP stain is a suitable procedure for the identification and counting of PL in experimentally induced periapical granulomas in rats (AU)