Inflammation Of Periapical Tissues Research Articles

Ferroptosis of macrophages facilitates bone loss in apical periodontitis via NRF2/FSP1/ROS pathway

Apical periodontitis (AP) is an infectious disease that causes periapical tissue inflammation and bone destruction. Ferroptosis, a novel type of regulated cell death, is closely associated with inflammatory diseases and the regulation of bone homeostasis. However, the exact involvement of ferroptosis in the bone loss of AP is not fully understood. In this study, human periapical tissues were collected, and a mouse model was established to investigate the role of ferroptosis in AP. Colocalization staining revealed that ferroptosis in macrophages contributes to the inflammatory bone loss associated with AP. A cell model was constructed using RAW 264.7 cells stimulated with LPS to further explore the mechanism underlying ferroptosis in macrophages upon inflammatory conditions, which exhibited ferroptotic characteristics. Moreover, downregulation of NRF2 was observed in ferroptotic macrophages, while overexpression of NRF2 upregulated the level of FSP1, leading to a reduction in reactive oxygen species (ROS) in macrophages. Additionally, ferroptotic macrophages released TNF-α, which activated the p38 MAPK signaling pathway and further increased ROS accumulation in macrophages. In vitro co-culture experiments demonstrated that the osteogenic ability of mouse bone marrow stromal cells (BMSCs) was suppressed with the stimulation of TNF-α from ferroptotic macrophages. These findings suggest that the TNF-α autocrine-paracrine loop in ferroptotic macrophages can inhibit osteogenesis in BMSCs through the NRF2/FSP1/ROS signaling pathway, leading to bone loss in AP. This study highlights the potential therapeutic value of targeting ferroptosis in the treatment of inflammatory bone diseases.

Interradicular Canals in 213 Mandibular and 235 Maxillary Molars by Means of Micro–computed Tomographic Analysis: An Ex Vivo Study

IntroductionBacteria and/or toxin residuals in the furcation areas of mandibular and maxillary molars can be the cause of persistent periapical tissue inflammation before or after an endodontic treatment. MethodsThe objective of this ex vivo study was to investigate the frequency of interradicular canals and diverticula in first and second mandibular and first and second maxillary molars by means of micro–computed tomographic imaging. Five hundred thirteen extracted molars, 211 mandibular molars and 302 maxillary molars, were included in this investigation. The area between the pulp chamber floor (PCF) and the furcation area was examined, and the data obtained were evaluated with imaging software that generated the corresponding 3-dimensional images. The results were analyzed by means of descriptive statistics. ResultsInterradicular canals were observed in 2.8% and 0.3% of the mandibular and maxillary molars, respectively. The diverticula (blind-ended interradicular canals) originated either at the furcation area or at the PCF. The diverticula frequency observed in mandibular molars was 3.3% (PCF) and 4.3% (bifurcation). The maxillary molar diverticula frequency observed was 2.0% (trifurcation), with none of them originating at the PCF. Altogether (n = 513) diverticula originated more frequently from the PCF (59.1%) than from the furcation area (40.9%). ConclusionsAlthough interradicular canals as well as diverticula were observed in a relatively small number of the investigated molars, practitioners should always be aware of their existence because without an adequate chemical debridement/disinfection of the pulp chamber root canal system, successful endodontic treatment could be compromised in up to 10% of the cases.

Application of High-Frequency Conduction for Persistent Apical Periodontitis: A Case Report

We report the case of a 39-year-old male with Persistent Apical Periodontitis (PAP) caused by infection in an uninstrumented area, wherein conventional chemical root canal treatment is not possible, which was sterilized via highfrequency conduction. He underwent root canal filling after multiple endodontic treatments for tooth #4. As symptoms recurred, he was referred to our department with the chief complaint of dull pain during mastication. Present symptoms were percussion pain of the tooth, buccal mucosa swelling at the apical portion, and grade 1 mobility. Radiography revealed inadequate root canal filling. A radiolucent image 5×6 mm in diameter and with an unclear boundary was observed around the apex. External root resorption was mainly observed in the apical foramen, with a crown root ratio of approximately 1:1. Using 6% sodium hypochlorite under dental microscopy, chemomechanical root canal preparation was performed. Passive ultrasonic irrigation and calcium hydroxide application were conducted three times; however, periapical tissue inflammation did not subside. Therefore, the patient was diagnosed with PAP, and the uninstrumented area was sterilized via high-frequency conduction. High-frequency currents were applied to the apex, root surface, and periapical lesion at 500 kHz and 90 V; periapical tissue inflammation resolved after 2 weeks. Subsequently, the root canal was filled. Follow-up radiography revealed a bone regeneration-like image at 2 months. Bone defects healed at 11 months. Although surgical endodontic therapy is conventionally performed in PAP patients, high-frequency conduction could be a minimally invasive nonsurgical endodontic treatment option for uninstrumented areas in PAP patients.

Dental Caries-A Huge Challenge for Public Health

The problem of caries disease has become one of the major challenges for public health in countries around the world, while becoming one of the most worrying health phenomena in the world. It is obvious that caries is a pathological process of local nature, leading to decalcification of enamel and dentin, decomposition of hard tooth tissues and, consequently, formation of a cavity, but also a serious risk factor for other diseases. Many studies have shown a significant relationship between periapical tissue inflammation and cardiovascular disease [1-3], diabetes [4,5] and systemic oxidative stress [6].

An update of knowledge on the regulatory role of Treg cells in apical periodontitis.

Apical periodontitis (AP) is a prevalent infectious and inflammatory disorder that involves inflammation of periapical tissues and the disintegration of alveolar bone. AP may eventually lead to tooth loss if not timely treated. This disease is caused by pathogenic bacteria in the necrotic pulps and root canals, thereby triggering responses from the innate and adaptive immune system of the periapical tissues. Regulatory T (Treg) cells play a major role in maintaining immune homoeostasis and immunological self-tolerance; however, these only account for roughly 5%-10% of human peripheral CD4+ T cells. Several studies have examined the possible role and underlying mechanism of Treg cells in different inflammatory and autoimmune disorders to facilitate the development of novel treatments for these diseases. Recent studies have indicated that Treg cells may gather at the sites of infection, thus limiting the generation of immune responses and bone resorption in the periapical area. This review will summarize studies regarding the presence and regulatory role of Treg cells in AP.

Dental assessment of odontogenic maxillary sinusitis, aided by Cone Beam Computed Tomography.

To identify tooth diseases as potential causative factors in the development of maxillary sinus lesions, with the aid of clinical examination combined with Cone Beam Computed Tomography (CBCT), in the patients with persistent sinus-like ailments, unresponsive to routine treatment offered by otolaryngologists. In 44 patients with suspected odontogenic maxillary sinusitis, a dental examination with tooth vitality test was carried out, in conjunction with CBCT. The study involved 29 women and 15 men (age range 19-69 years, mean age 43 (SD = 13.9) years). In 15 (34.1%) patients the odontogenic lesions were encountered in maxillary sinuses. A total of 33 causative teeth were identified, of which 13 (39%) were after root canal treatment (RCT). Only one of the teeth had a properly reconstructed crown, and only one tooth had the root canals properly filled-in. Most frequently, the lesions in the sinuses were attributed to the inflammation of periapical tissues; the first molar having been established as the most common causative tooth. A detailed dental examination, pursued in conjunction with CBCT analysis, allow to diagnose odontogenic maxillary lesions. The incidence of long-term ailments originating in the maxillary sinuses should prompt a detailed assessment of the teeth, especially those after RCT.

Light-Activated Zirconium(IV) Phthalocyanine Derivatives Linked to Graphite Oxide Flakes and Discussion on Their Antibacterial Activity

In search of an effective antibacterial agent that is useful in photodynamic therapy, new derivatives of zirconium(IV) phthalocyanine (ZrPc) complexes were obtained and linked to graphite oxide flakes. In the syntheses of ZrPc derivatives, two bis-axially substituted ligands with terminal amino group and different lengths of linear carbon chain (C4 in 4-aminobutyric acid or C11 in 11-aminoundecanoic acid) were used. The optical properties (absorption and photoluminescence spectra) of ZrPcs and the composites were examined. Broadband red–near-infrared lamp was tested as an external stimulus to activate ZrPcs and the composites. Optical techniques were used to show generation of singlet oxygen during irradiation. Considering the application of graphite oxide-based materials as bacteriostatic photosensitive additives for endodontic treatment of periapical tissue inflammation, the antibacterial activity was determined on one Escherichia coli strain isolated directly from an infected root canal of a human tooth and one strain with silver and antibiotic resistance. Looking at the obtained results, modified levels of activity toward different bacterial strains are discussed.

BioRoot RCS Extracts Modulate the Early Mechanisms of Periodontal Inflammation and Regeneration

IntroductionThe balance between periapical tissue inflammation and regeneration after the removal of necrotic/infected tissues is pivotal in determining the success of endodontic treatment. This study was designed to investigate the effect of silicate-based root canal sealer BioRoot RCS (BRCS; Septodont, Saint-Maur-des-Fossés, France) on modulating the inflammatory mechanisms and early steps of regeneration initiated by human periodontal ligament (PDL) fibroblasts. MethodsSamples of BRCS and Pulp Canal Sealer (PCS; SybronEndo, Orange, CA) were incubated in culture medium to obtain material extracts. To simulate bacterial infection and endodontic sealer use, PDL fibroblasts were stimulated with lipopolysaccharides and cultured with material extracts. The secretion of proinflammatory cytokine (interleukin 6) and growth factor (transforming growth factor beta 1) were quantified by enzyme-linked immunosorbent assay. Inflammatory cell recruitment sequence was investigated using a human inflammatory monocytic cell line (THP-1) that can be activated into macrophage-like cells. The adhesion of THP-1 to endothelial cells (human umbilical vein endothelial cells) was studied using fluorescent THP-1, their migration using Boyden chambers, and their activation into macrophage-like cells using a cell adhesion assay. The proliferation of PDL fibroblasts was quantified by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, whereas the migration of PDL stem cells was investigated using Boyden chambers after immunofluorescence and reverse transcription polymerase chain reaction characterization. ResultsInterleukin 6 secretion decreased with BRCS, whereas it increased with PCS. Transforming growth factor beta 1 secretion significantly increased only with BRCS. The material extracts did not affect THP-1 adhesion to human umbilical vein endothelial cells, but only BRCS inhibited their migration. Moreover, activation of THP-1 decreased with BRCS and to a lesser extent with PCS. Finally, BRCS increased PDL fibroblast proliferation without affecting PDL stem cell migration. By contrast, PCS decreased PDL fibroblast proliferation and PDL stem cell migration. ConclusionsThis work shows that the endodontic sealers modulate the PDL inflammatory and regeneration potentials in vitro. It demonstrates that BRCS has anti-inflammatory effects and the potential to promote tissue regeneration.

The Presence and involvement of interleukin-17 in apical periodontitis.

Apical periodontitis (AP) is a chronic inflammatory disease characterized by periapical tissue inflammation and destruction of the associated alveolar bone. It is caused by microbial infections within the root canal and the resultant host immune responses in the periapical tissues. The proinflammatory cytokine interleukin (IL)-17 has been shown to play an important role in many inflammatory diseases. There is increasing evidence of the presence of IL-17 in AP, which might be associated with disease pathogenesis. Moreover, several animal studies indicate the potential role of IL-17 in periapical inflammation and the resultant bone resorption in AP. This article reviews recent studies regarding the collective invitro, invivo and clinical evidence of the presence and involvement of IL-17 in AP. A search related to IL-17 in apical periodontitis was conducted on PubMed, EMBASE and Web of Science databases using keywords and controlled vocabulary. Two independent reviewers first screened titles and abstracts and then the full texts that were included. A total of 25 papers were identified, of the 25 included articles, 7 involved laboratory studies on cell cultures, 11 involved animal experimentations, and 7 were observational studies using human clinical samples. In conclusion, evidence for the presence of IL-17 in AP from human and animal models is clear. However, there is relatively little information currently available that would highlight the specific role of IL-17 in AP.

Cross Talk between Apical Periodontitis and Metabolic Disorders: Experimental Evidence on the Role of Intestinal Adipokines and Akkermansia muciniphila

IntroductionInfection and dysbiosis present a close relationship with metabolic diseases although the influence of apical periodontitis (AP) in this context needs further investigation. This study evaluated the influence of AP in a rat model of metabolic syndrome induced by 10% fructose supplementation. MethodsMale Wistar rats were used. Animals that received a high-fructose diet (HFD, n = 30) or filtered water (control, n = 30) were subdivided into the following groups:(1) without induction of AP (no AP, n = 10 each),(2) with AP induction 2 weeks before euthanasia (AP 14 days, n = 10 each), and(3) with AP induction 4 weeks before euthanasia (AP 28 days, n = 10 each). ResultsHFD triggered metabolic syndrome, as indicated by the induction of overweight and hyperglycemia, besides polydipsia, regardless of the AP induction. Serum or intestinal tumor necrosis factor, interleukin 1 beta, and interleukin 6 levels were undetectable, regardless of the experimental group. Serum leptin and adiponectin levels were significantly elevated in the HFD group without AP induction. The intestinal levels of leptin were significantly increased in the groups with 28 days of AP induction despite HFD. A significant elevation of liver glutathione levels was observed in animals submitted to HFD and AP for 14 days. AP induction (14 or 28 days) led to pulp and periapical tissue inflammation without any influence of HFD. Either HFD or AP induction led to dysbiosis, as indicated by a significant reduction of fecal A. muciniphila expression. ConclusionsWe provide novel evidence that AP can have systemic impacts on metabolic disorders, likely by modulating intestinal metabolism and microbiota.

Inflammation of periapical tissues of the teeth, complicated by a fistula of the cheek skin

Inflammation of the periapical tissue may lead to the development of complications involving cooperation between many medical specialists. The cutaneous fistula is a rare complication of chronic alveolus inflammation being diagnostic and therapeutic challenge due to unspecific symptoms. The correct diagnostic protocol may influence correct diagnosis, localization of the primary site of inflammation and the appropriate treatment.

Microbial community in persistent apical periodontitis: a 16S rRNA gene clone library analysis.

To characterize the microbial composition of persistent periapical lesions of root filled teeth using a molecular genetics approach. Apical lesion samples were collected from 12 patients (23-80years old) who visited the Kyushu University Hospital for apicectomy with persistent periapical lesions associated with root filled teeth. DNA was directly extracted from each sample and the microbial composition was comprehensively analysed using clone library analysis of the 16S rRNA gene. Enterococcus faecalis, Candida albicans and specific fimA genotypes of Porphyromonas gingivalis were confirmed using polymerase chain reaction (PCR) analysis with specific primers. Bacteria were detected in all samples, and the dominant findings were P.gingivalis (19.9%), Fusobacterium nucleatum (11.2%) and Propionibacterium acnes (9%). Bacterial diversity was greater in symptomatic lesions than in asymptomatic ones. In addition, the following bacteria or bacterial combinations were characteristic to symptomatic lesions: Prevotella spp., Treponema spp., Peptostreptococcaceae sp. HOT-113, Olsenella uli, Slackia exigua, Selemonas infelix, P.gingivalis with type IV fimA, and a combination of P.gingivalis, F.nucleatum, and Peptostreptococcaceae sp. HOT-113 and predominance of Streptococcus spp. On the other hand, neither Enterococcus faecalis nor C. albicans were detected in any of the samples. Whilst a diverse bacterial species were observed in the persistent apical lesions, some characteristic patterns of bacterial community were found in the symptomatic lesions. The diverse variation of community indicates that bacterial combinations as a community may cause persistent inflammation in periapical tissues rather than specific bacterial species.

Root Canal System Analysis with a Group of First Permanent Molars of Upper and Lower Jaw

Abstract A progressive bacteria invasion on tooth tissues leads to pulp inflammation, microabscesses of the pulp, destruction and in consequence inflammation of periapical tissues. Therefore the aim of endodontic treatment is three dimensional debridement of a root canal from the vent in pulp chamber to the physiological narrowing. Therefore the aim of the study is analysis of root canal configuration, number of canals, presence of lateral canals and canal delta with the group of first permanent molars. At the same time the accuracy of the radiological examination (x-ray images) is estimated due to comprehension of X-ray images performed before teeth preparation with root canal system and after observation of transversal cuts by means of light microscopy and microtomography. This establishment is presented through the differences in conventional radiological image and clinical assessment.

The use of physiotherapy in the regeneration of periapical bone structures of the teeth, prepared to load the prosthetic

The aim of this work was to investigate whether the use of magnetoledotherapy will accelerate the elimination of osteolytic lesions of the dental periapical area, and provide for prosthetic treatment. What impact on time of healing does the inflammatory change location, type of treatment or patient's age have? 69 patients underwent the examination. The problem of osteolytic lesions in the course of protracted or protracted acute dental periapical tissue inflammation was determined. Patients were divided into two research groups: group L - treated with magnetoledotherapy and group K - treated without the support of magnetoledotherapy. In the first group we applied the electromagnetic field, generated using the Viofor JPS Clinic apparatus. Our studies have confirmed the effectiveness of magnetoledotherapy in the accelerated decommissioning of the osteolytic lesion. This provides evidence of the appropriateness of this method in the treatment of protracted dental periapical tissue inflammation, in teeth qualified for prosthetic load. Magnetostimulation combined with LED energy is an adjunctive procedure, adopted in order to eliminate osteolytic inflammatory changes of dental periapical tissues. It can be used in all age groups with the same good result. After applying magnetoledotherapy, in the course of the dental periapical tissue repair process of tooth treated endodontically for the first time as well as reendodontically, no differences were found. This shows the opportunity of using magnetoledotherapy in all cases of protracted periapical tissue inflammation.

Th1 and Th2-like Protein Balance in Human Inflammatory Radicular Cysts and Periapical Granulomas

IntroductionChronic dental periapical lesions result from chronic inflammation of periapical tissues caused by continuous antigenic stimulation from infected root canals. Recent findings have suggested that T helper (Th) 1 and Th2-like cytokines are important in the pathogenesis of chronic periapical inflammatory diseases. However, the mechanisms regulating these immunoinflammatory pathways have not been fully elucidated. Thus, the aim of this study was to evaluate interleukin (IL)-4, IL-12, and interferon γ (IFN-γ) protein levels in human radicular cysts and periapical granulomas. MethodsArchived samples of cysts (n = 52) and granulomas (n = 27) were sectioned and submitted to immunohistochemistry to evaluate the tissue expression of IL-4, IL-12, and IFN-γ. The data were analyzed using the Mann-Whitney U test (P < .05). ResultsAn increased expression of IFN-γ was observed in radicular cysts. IL-4 expression was stronger in periapical granulomas than in radicular cysts. IL-12 was not detected in any of the samples. ConclusionsOur study showed that IFN-γ protein levels are increased in radicular cysts, whereas IL-4 expression is stronger in samples of periapical granulomas. Further studies are necessary to elucidate the signaling pathways mediated by these cytokines and to facilitate the development of more effective periapical disease management strategies.

The role of intracanal medication in root canal treatment.

The role of intracanal medication as a root canal dressing is re-examined. In pulpectomy and some root canal treatments, where the root canal contains vital pulp tissue, it is doubtful whether a routine intracanal medicament is needed. In infected root canals, intracanal medication has been advocated for many purposes. An intracanal medicament is used to: (i) eliminate any remaining bacteria after canal instrumentation; (ii) reduce inflammation of periapical tissues and pulp remnants; (iii) render canal contents inert and neutralize tissue debris; (iv) act as a barrier against leakage from the temporary filling; (v) help to dry persistently wet canals. However, most of the indications for intracanal medicaments are questionable. Intracanal medicaments should only be used for root canal disinfection as part of controlled asepsis in infected root canals, and their role is secondary to cleaning and shaping of the root canal. Thorough canal debridement and adequate canal preparation are more pertinent, and their importance is emphasized. Bacteriological sampling may be necessary if a tooth does not respond to treatment, to help in the choice of intracanal medicament.