scholarly journals Inhibition of the CXCL9-CXCR3 axis suppresses the progression of experimental apical periodontitis by blocking macrophage migration and activation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tatsuya Hasegawa ◽  
V. Venkata Suresh ◽  
Yoshio Yahata ◽  
Masato Nakano ◽  
Shigeto Suzuki ◽  
...  

AbstractApical periodontitis (AP) is an acute or chronic inflammatory disease caused by complex interactions between infected root canal and host immune system. It results in the induction of inflammatory mediators such as chemokines and cytokines leading to periapical tissue destruction. To understand the molecular pathogenesis of AP, we have investigated inflammatory-related genes that regulate AP development. We found here that macrophage-derived CXCL9, which acts through CXCR3, is recruited by progressed AP. The inhibition of CXCL9 by a CXCR3 antagonist reduced the lesion size in a mouse AP model with decreasing IL-1β, IL-6 and TNFα expression. The treatment of peritoneal macrophages with CXCL9 and LPS induced the transmigration and upregulation of osteoclastogenic cytokines such as IL-1β, IL-6 and matrix metalloprotease 2, a marker of activated macrophages. This suggests that the CXCL9-CXCR3 axis plays a crucial role in the development of AP, mediated by the migration and activation of macrophages for periapical tissue destruction. Our data thus show that CXCL9 regulates the functions of macrophages which contribute to AP pathogenesis, and that blocking CXCL9 suppresses AP progression. Knowledge of the principal factors involved in the progression of AP, and the identification of related inflammatory markers, may help to establish new therapeutic strategies.

2010 ◽  
Vol 9 (1) ◽  
pp. 63
Author(s):  
Indrya Kirana Mattulada

Bacteria and their products play a fundamental role in the initiation, propagation andpersistence of pulpal and periradicular diseases. Consequently one of the major goalsof endodontic treament is to eliminate all bacteria from the root canal space.Elimination of microorganism from infected root canal is a complicated task.Numerous measures have been described to reduce the numbers of root canalmicroorganism, including the use of various instrumentation techniques, irrigationregimens, and intracanal medication. In endodontic treatment, there are severalmedicament used traditionally. They are phenolic, aldehyde, halogen, calciumhydroxide, and antibiotic. The aim of this paper is to discuss about indication,contraindication and effect of each medicament.


2016 ◽  
Vol 113 (3) ◽  
pp. 722-727 ◽  
Author(s):  
Duraisamy Ponnusamy ◽  
Elena V. Kozlova ◽  
Jian Sha ◽  
Tatiana E. Erova ◽  
Sasha R. Azar ◽  
...  

Necrotizing fasciitis (NF) caused by flesh-eating bacteria is associated with high case fatality. In an earlier study, we reported infection of an immunocompetent individual with multiple strains of Aeromonas hydrophila (NF1–NF4), the latter three constituted a clonal group whereas NF1 was phylogenetically distinct. To understand the complex interactions of these strains in NF pathophysiology, a mouse model was used, whereby either single or mixed A. hydrophila strains were injected intramuscularly. NF2, which harbors exotoxin A (exoA) gene, was highly virulent when injected alone, but its virulence was attenuated in the presence of NF1 (exoA-minus). NF1 alone, although not lethal to animals, became highly virulent when combined with NF2, its virulence augmented by cis-exoA expression when injected alone in mice. Based on metagenomics and microbiological analyses, it was found that, in mixed infection, NF1 selectively disseminated to mouse peripheral organs, whereas the other strains (NF2, NF3, and NF4) were confined to the injection site and eventually cleared. In vitro studies showed NF2 to be more effectively phagocytized and killed by macrophages than NF1. NF1 inhibited growth of NF2 on solid media, but ExoA of NF2 augmented virulence of NF1 and the presence of NF1 facilitated clearance of NF2 from animals either by enhanced priming of host immune system or direct killing via a contact-dependent mechanism.


2015 ◽  
Vol 17 (2) ◽  
pp. 43
Author(s):  
Rodolfo Zeledón DDS, Esp ◽  
Carolina Ballestero DDS, Esp ◽  
Erick Hernández DDS. Esp ◽  
Tatiana Ramírez DDS, MSD ◽  
Marianela Benavides DDS, Esp ◽  
...  

The objective of this clinical study was to evaluate by polymerase chain reaction (PCR) the antimicrobial efficacy and the outcome of an endodontic protocol treatment (EPT) performed by under-graduated dental students on infected root canals associated with periapical lesions. Fifty-six patients attending for treatment of pulp necrosis and apical periodontitis were included. A specific EPT approach was performed and DNA extracts were taken at the baseline (S1), after a disinfection-neutralization procedure (S2), post-chemomechanical preparation (S3) and after Intracanal medication (S4) for the presence of specific bacteria. The outcome of the EPT was assessed radiographically using the Periapical Index-system (PAI) after 18-month follow-up. An intergroup evaluation shows that when comparing S1 to S3, S1 to S4, S2 to S3, and S2 to S4, the presence of bacteria were significantly reduced (P < 0.05). Finally, S4 was not significantly reduced when compared with S3 (P > 0.05). The most prevalent species in their respect order were Actinomyces Israelii > Enterococcus Faecalis > Fusobacterium Nucleatum/Prevotella Nigrescens > Phorphyromonas Endodontalis. After the 18-month follow-up, the overall success rate of root canal – treated teeth was of 88% (PAI 1 or 2). This In Vivo study demonstrated that EPT significantly reduced the number of cases with positive results for the studied bacteria, showing a profound positive impact in the outcome of endodontic treatment of teeth diagnosed with Pulp Necrosis and Apical Periodontitis. 


2018 ◽  
Vol 6 (2) ◽  
pp. 389-396 ◽  
Author(s):  
Nexhmije Ajeti ◽  
Teuta Pustina-Krasniqi ◽  
Sonja Apostolska ◽  
Edit Xhajanka

OBJECTIVES: During the treatment of chronic apical periodontitis and pulp necrosis the main role is to irrigate the root canal.AIM: The aim of this in vivo study was to irrigate with 0.9% NaCl (Natrium Chloride), 2.5 % NaOCl (Sodium Hypochlorite Solution, Sigma Aldrich - Germany) and 2% CHX (Chlorhexidine Digluconate Solution, Sigma Aldrich - Spain) combined with Gaseous Ozone (Prozone WH, Austria).MATERIAL AND METHODS: This study was realised in the University Dentistry Clinical Centre of Kosovo (UDCCK), respectively in the Department of Endodontic and Dental Pathology, Dental Branch, Faculty of Medicine, Prishtina, Kosovo. The 40 subjects involved in this study belonged to both genders, in age between 15 -65 years. The sample selection was randomised. The retroalveolar radiography for each patient was taken in the suspected tooth. As a therapeutic plan the authors decided to disinfect the root canal with the irrigants, as follows: 2.5 % NaOCl, 2 % CHX and gaseous ozone.RESULTS: The statistical analyses were based on Kruskal - Vallis test, X - test, DF = 3, r < 0.01. In the isolated average number of the aerobe and anaerobe bacteria colonies, when gaseous ozone was used, there was the significant statistical difference.CONCLUSIONS: When gaseous ozone was combined with irrigants 0.9%, 2.5 % NaOCl and 2% CHX, it was concluded that the number of colonies of aerobic and anaerobic bacteria was reduced.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Sheela B. Abraham ◽  
Farah al Marzooq ◽  
Wan Harun Himratul-Aznita ◽  
Hany Mohamed Aly Ahmed ◽  
Lakshman Perera Samaranayake

Abstract Background There is limited data on the prevalence of Candida species in infected root canal systems of human teeth. We attempted to investigate the prevalence, genotype, virulence and the antifungal susceptibility of Candida albicans isolated from infected root canals of patients with primary and post-treatment infections in a UAE population. Methods Microbiological samples from 71 subjects with infected root canals were aseptically collected, and cultured on Sabouraud dextrose agar, and C. albicans was identified using multiplex polymerase chain reaction, and the isolates were further subtyped using ABC genotyping system. Their relative virulence was compared using further four archival samples of endodontic origin from another geographical region, and four more salivary isolates, as controls. The virulence attributes compared were biofilm formation, and production of phospholipase and haemolysin, and the susceptibility to nystatin, amphotericin B, ketoconazole, and fluoconazole was also tested. Results 4 out of 71 samples (5.6%) yielded Candida species. On analysis of variance among the groups, the intracanal isolates, mainly Genotype A, possessed a high degree of phospholipase and haemolysin activity (p < 0.05). The UAE and Finland isolates were stronger biofilm formers and had superior phospholipase production capacity compared with the salivary isolates. All isolates were sensitive to the antifungal chemicals used. The salivary isolates were more sensitive to fluoconazole compared to other groups (p < 0.05). Conclusion The prevalence of C. albicans in infected root canals of patients attending a dental hospital in UAE is low. The strains isolated were good biofilm formers, possessed strong phospholipase and haemolysin activity and were mostly of the genotype A. The fact that the root canal isolates possessed significant hydrolase activity, imply that they are equipped with virulence attributes necessary for survival within a harsh intracanal ecosystem.


2019 ◽  
Vol 133 (10) ◽  
pp. 1185-1196 ◽  
Author(s):  
Siroon Bekkering ◽  
Albert P. Limawan ◽  
Maria U. Nguyen ◽  
Lisa K. Widiasmoko ◽  
Hui Lu ◽  
...  

Abstract Atherosclerosis is a chronic inflammatory disease that has its origins in early life. Postnatal inflammation exacerbates atherosclerosis, but the possible effect of intrauterine inflammation is largely unexplored. Exposure to inflammation in utero is common, especially in infants born preterm, who have increased cardiovascular risk in adulthood. We hypothesised that exposure to inflammation before birth would accelerate the development of atherosclerosis, with the most severe atherosclerosis following exposure to both pre- and postnatal inflammation. Here we studied the effect of prenatal and postnatal inflammation on the development of atherosclerosis by combining established techniques for modelling histological chorioamnionitis and atherosclerosis using apolipoprotein E (ApoE) knockout mice. A single intra-amniotic (IA) injection of lipopolysaccharide (LPS) caused intrauterine inflammation, and increased atherosclerosis at 13 weeks of postnatal age. In mice exposed to postnatal LPS, chorioamnionitis modulated subsequent responses; atherosclerotic lesion size, number and severity were greatest for mice exposed to both intrauterine and postnatal inflammation, with a concomitant decrease in collagen content and increased inflammation of the atherosclerotic plaque. In conclusion, pre- and postnatal inflammation have additive and deleterious effects on the development of atherosclerosis in ApoE knockout mice. The findings are particularly relevant to preterm human infants, whose gestations are frequently complicated by chorioamnionitis and who are particularly susceptible to repeated postnatal infections. Human and mechanistic studies are warranted to guide preventative strategies.


2015 ◽  
Vol 56 (3) ◽  
pp. 169-175 ◽  
Author(s):  
Masataka Suehara ◽  
Yosuke Sano ◽  
Ryo Sako ◽  
Natsuko Aida ◽  
Rie Fujii ◽  
...  

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