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AIM: To evaluate the role of regulatory T lymphocytes (Tregs) in the presence or absence of the synthetic ligand Pam3Cys during the progression of periapical lesion in wild-type (WT) and toll-like receptor 2 knockout (TLR2KO) mice. METHODOLOGY: A total of 130 C57BL/6 male WT and TLR2KO mice were allocated into control (n = 5) and experimental (periapical lesion induction) (n = 10) groups. In specific groups (WT+Pam3cys and TLR2KO+Pam3cys), the synthetic ligand Pam3cys was administered intraperitoneally every 7 days, according to the experimental period (14, 21 and 42 days). At the end of those periods, the animals were euthanized, and the mandible and the spleen were submitted to histotechnical processing. Mandible histological sections were analysed by haematoxylin and eosin, TRAP histoenzymology and immunohistochemistry (FOXP3, RANK, RANKL and OPG). Spleen sections were analysed by immunohistochemistry (FOXP3). RESULTS: The inflammatory infiltrate and bone resorption were more intense in the TLR2KO group compared to the WT group. The animals that received the Pam3cys had smaller periapical lesions when compared to the animals that did not receive the ligand (p < .05). TLR2KO animals showed a significant increase in the number of osteoclasts when compared to TLR2KO+Pam3cys group (p < .05). At 21 days, the WT+Pam3cys group had a lower number of osteoclasts when compared to the WT animals (p = .02). FOXP3 expression was more intense in the WT+Pam3cys groups when compared to the WT animals in the 42 days (p = .03). In the spleen analysis, the WT+Pam3cys group also had a higher expression of FOXP3 when compared to the WT animals at 14 and 42 days (p = .02). Concerning RANKL, there was a reduction in staining in the KOTLR2+Pam3cys groups at 21 and 42 days (p = .03) and a higher binding ratio between RANK/RANKL in animals that did not receive the ligand. CONCLUSION: Administration of the Pam3cys increased the proliferation of Tregs, showed by FOXP3 expression and prevented the progression of the periapical lesion in WT mice. On the other hand, in the TLR2KO animals, Treg expression was lower with larger areas of periapical lesions. Finally, systemic administration of the Pam3cys in KO animals was able to limit the deleterious effects of the absence of the TLR2 receptor.
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Osteoclastos , Receptor Toll-Like 2 , Ratones , Masculino , Animales , Osteoclastos/metabolismo , Receptor Toll-Like 2/metabolismo , Ligandos , Ratones Endogámicos C57BL , Ligando RANK/farmacología , Ligando RANK/metabolismo , Factores de Transcripción Forkhead/metabolismo , Ratones NoqueadosRESUMEN
OBJECTIVE: To evaluate the effects of NLRP3 inflammasome inhibition or knockout in experimental apical periodontitis (AP) induced in mice. METHODS: The experimental AP was induced by pulpal exposure. To evaluate NLRP3-specific inhibitor medication (MCC950), WT mice received intraperitoneal injections, while the control received PBS (n = 10). In addition, to evaluate NLRP3 knockout, 35 wild-type (WT) and 35 NLRP3-/- mice were divided into a control group (without pulpal exposure, n = 5) and three experimental groups: after 2, 14 and 42 days after pulpal exposure (n = 10). Microscopic and molecular analyzes were carried out using a significance level of 5%. RESULTS: Exposure to MCC950 did not affect the periapical lesion size after 14 days (P = 0.584). However, exposed mice had a lower expression of IL-1ß, IL-18 and caspase-1 (P = 0.010, 0.016 and 0.002, respectively). Moreover, NLRP3-/- mice showed a smaller periapical lesion after 14 and 42 days (P = 0.023 and 0.031, respectively), as well as a lower expression of IL-1ß after 42 days (P < 0.001), of IL-18 and caspase-1 after 14 (P < 0.001 and 0.035, respectively) and 42 days (P = 0.002 and 0.002, respectively). NLRP3-/- mice also showed a lower mRNA for Il-1ß, Il-18 and Casp1 after 2 (P = 0.002, 0.036 and 0.001, respectively) and 14 days (P = 0.002, 0.002 and 0.001, respectively). CONCLUSIONS: NLRP3 inflammasome inhibition or knockout can attenuate the inflammatory events that result in the periapical lesion (AP) formation after pulpal exposure in mice. CLINICAL RELEVANCE: The NLRP3 inflammasome may be a therapeutic target for AP, and new approaches may verify the impact of its inhibition (through intracanal medications or filling materials) on the bone repair process and treatment success.
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Modelos Animales de Enfermedad , Indenos , Inflamasomas , Ratones Noqueados , Proteína con Dominio Pirina 3 de la Familia NLR , Periodontitis Periapical , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Ratones , Inflamasomas/metabolismo , Sulfonamidas/farmacología , Furanos/farmacología , Caspasa 1/metabolismo , Interleucina-1beta/metabolismo , Sulfonas/farmacología , Ratones Endogámicos C57BL , MasculinoRESUMEN
BACKGROUND: The conicity of the root canals of primary teeth is an important measure for endodontic therapies. However, determining this conicity depends on the methods employed, which requires further investigation. AIM: The aim of this study was to determine the conicity of the root canals of the upper and lower primary second molars using nanotomography (nCT). DESIGN: An in vitro study was performed using nine primary second molars, both upper and lower, subjected to nCT. Comparisons between the diameters of root canals were performed between the thirds (cervical-D0, middle-D5, and apical-D7). The conicity (%) was determined for each root canal from cervical to apical. Data were statistically analyzed with a significance level of 5%. RESULTS: The conicity ranged from 2% to 8% for the upper primary second molars. Significant differences in root canal diameter between the thirds (D0, D5, and D7 points) were observed in the mesio- and distobuccal roots (p < .05), but not in the palatal roots (p > .05). For the lower primary second molars, the conicity ranged from 2% to 17%, as well as significant differences in root canal diameter between the thirds (D0, D5, and D7 points) were observed in all roots (distal, mesiobuccal, and mesiolingual; p < .05). CONCLUSION: The conicity of the upper primary second molars was different from that of the lower ones, which showed a greater variability.
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AIM: To investigate if there was an association between genetic polymorphisms in tumour necrosis factor (TNF)-⺠and its receptors TNFRSF1A and TNFRSF1B with persistent apical periodontitis (PAP) in Brazilian subjects. METHODOLOGY: Patients who had pulpal necrosis and apical periodontitis at the time of treatment, with at least 1-year of follow-up after non-surgical root canal treatment were recalled. Three hundred and seventy eight subjects were included, 150 subjects with signs/symptoms of PAP and 228 subjects with root canal-treated teeth exhibiting healthy perirradicular tissues (healed). Genomic DNA was extracted from saliva and used for TNF-⺠(rs1800629), TNFRSF1A (rs1800693) and TNFRSF1B (rs1061622) genotyping by real-time PCR. Genotypes and alleles frequencies were evaluated by c2 or Fisher's exact tests and odds ratios were implemented (α = 5%). RESULTS: The genetic polymorphism in TNF-α (rs1800629) was associated as a protective factor for the development of PAP (p < .05), once subjects who presented at least one allele A (AA+AG X GG), had a higher chance to lesion repair (p < .05). The polymorphisms rs1800693 and rs1061622 in TNF receptors (TNFRSF1A and TNFRSF1B, respectively) were not associated with the development of PAP (p > .05). CONCLUSIONS: The observed results demonstrate that polymorphism in TNF-α but not in its receptors is associated with PAP.
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Polimorfismo Genético , Factor de Necrosis Tumoral alfa , Humanos , Factor de Necrosis Tumoral alfa/genética , BrasilRESUMEN
Parasitemia and inflammatory markers are cross-sectionally associated with chronic Chagas cardiomyopathy (CCC) among patients with Trypanosoma cruzi. However, the prospective association of the parasite load and host immune response-related characteristics with CCC (that is, progressors) among T. cruzi seropositive individuals has only been partially defined. In a cohort of T. cruzi seropositive patients in Montes Claros and São Paulo, Brazil who were followed over 10 years, we identified the association of a baseline T. cruzi parasite load and systemic markers of inflammation with a decline in cardiac function and/or the presence of cardiac congestion 10 years later. The progressors (n = 21) were individuals with a significant decline in the left ventricular ejection fraction and/or elevated markers of cardiac congestion after 10 years. The controls (n = 31) had normal markers of cardiac function and congestion at the baseline and at the follow-up. They were matched with the progressors on age, sex, and genetic ancestry. The progressors had higher mean parasite loads at the baseline than the controls (18.3 vs. 0.605 DNA parasite equivalents/20 mL, p < 0.05). Of the 384 inflammation-related proteins analyzed, 47 differed significantly at a false discovery rate- (FDR-) corrected p < 0.05 between the groups. There were 44 of these 47 proteins that were significantly higher in the controls compared to in the progressors, including the immune activation markers CCL21, CXCL12, and HCLS1 and several of the tumor necrosis factor superfamily of proteins. Among the individuals who were seropositive for T. cruzi at the baseline and who were followed over 10 years, those with incident CCC at the 10-year marker had a comparatively higher baseline of T. cruzi parasitemia and lower baseline markers of immune activation and chemotaxis. These findings generate the hypothesis that the early impairment of pathogen-killing immune responses predisposes individuals to CCC, which merits further study.
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Enfermedad de Chagas , Parásitos , Trypanosoma cruzi , Humanos , Animales , Trypanosoma cruzi/genética , Brasil/epidemiología , Parasitemia , Volumen Sistólico , Función Ventricular Izquierda , ADN , InflamaciónRESUMEN
BACKGROUND: To investigate if 5-LO selective inhibitor (MK-886) could be used for systemic treatment of experimentally induced apical periodontitis in a mouse model. METHODS: Twenty-four C57BL/6 mice were used. After coronal opening, a solution containing Escherichia coli LPS (1.0 µg/µL) was inoculated into the root canals of the lower and upper right first molars (n = 72 teeth). After 30 days apical periodontitis was established, and the animals were treated with MK-886 (5 mg/kg), a 5-LO inhibitor, for 7 and 14 days. The tissues were removed for histopathological and histometric analyses, evaluation of osteoclast number and gene expression for receptor activator of nuclear factor kappa-B (Tnfrsf11a), receptor activator of nuclear factor kappa-B ligand (Tnfsf11), osteoprotegerin (Tnfrsf11b), tartrate-resistant acid phosphatase (Acp5), matrix metalloproteinase-9 (Mmp9), cathepsin K (Ctsk) and calcitonin receptor (Calcr). Statistical data analysis was performed using Kruskal Wallis followed by Dunn's tests (α = 0.05). RESULTS: Administration of MK-886 for 7 days exerted no effect on apical periodontitis progression compared to LPS inoculation without treatment (p = 0.3549), while treatment for 14 days exacerbated bone loss (p < 0.0001). Administration of MK-886 enhanced osteoclastogenesis signaling and osteoclast formation within 7 days (p = 0.0005), but exerted no effect at 14 days (p > 0.9999). After 7 days of treatment, MK-886 induced mRNA expression for Acp5 (p = 0.0001), Calcr (p = 0.0003), Mmp9 (p = 0.0005) and Ctsk (p = 0.0008), however no effect in those gene expression was observed after 14 days (p > 0.05). CONCLUSION: Systemic treatment with MK-886 exacerbated LPS-induced apical periodontitis in a mouse model.
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Metaloproteinasa 9 de la Matriz , Periodontitis Periapical , Ratones , Animales , Araquidonato 5-Lipooxigenasa/metabolismo , Lipopolisacáridos/farmacología , Ratones Endogámicos C57BL , Periodontitis Periapical/metabolismo , OsteoclastosRESUMEN
AIM: The aim of this study was to evaluate the IFI16 and IFN-α/ß receptors expression during the genesis and development of experimental apical periodontitis (AP) in mice teeth. METHODOLOGY: Apical periodontitis was induced in the lower first molars of 40 C57BL/6 mice. They were divided according to the experimental periods 2, 7, 14, 21 and 42 days (n = 8 per group). Five animals were used as a control group (without AP). Specimens were submitted to histological processing for description of the inflammatory process, immunostaining for the presence/absence and localization of IFI16 and IFN-α/ß receptors (qualitative and semi-quantitative analysis) and tartrate-resistant acid phosphatase (TRAP) histoenzimology. RESULTS: The results showed a gradual development of AP over the experimental times. The expression of IFI16 was noticeably more exacerbated in the experimental early period (day 2) whilst the lowest expression was observed in the control group (p = .02). For IFN-α/ß receptors, a higher intensity staining was observed 42 days after AP induction, that was statistically different from the control group (p = .02). In addition, the number of TRAP-positive cells was higher on the later periods (days 21 and 42; p < .001). CONCLUSION: IFI16 protein expression was highest during the early periods after AP induction in mice teeth, whilst IFN-α/ß receptor expression was highest after AP became established.
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Interferón gamma , Proteínas Nucleares/metabolismo , Periodontitis Periapical , Fosfoproteínas/metabolismo , Receptor de Interferón alfa y beta/metabolismo , Animales , Ratones , Ratones Endogámicos C57BL , Diente Molar/patología , Osteoclastos/metabolismo , Periodontitis Periapical/patologíaRESUMEN
Different types of brackets seem to influence the disruption of the oral microbial environment. Therefore, the aim of this study was to evaluate the influence of self-ligating brackets on the gingival crevicular fluid levels of the putative periodontal pathogens Aggregatibacter actinomycetemcomitans sorotype a (Aaa), Tannerella forsythia, Fusobacterium nucleatum, and Porphyromonas gingivalis. Sixty samples of crevicular fluid of twenty patients (11 boys and 9 girls) were analysed at baseline (T0) and after 30 (T1) and 60 (T2) days of bonding of the self-ligating (In-Ovation®R, Dentsply, GAC or SmartClip™, 3 M Unitek, Monrovia, CA, USA) and of one conventional bracket (Gemini™, 3 M Unitek, Monrovia, CA, USA) used with elastomeric ligatures. Total DNA from samples was extracted using CTAB-DNA precipitation method and Real-time PCR was performed to analyse bacterial level. Non-parametric Friedman and Wilcoxon tests were used for data analysis (p value of < 0.05). F. nucleatum presented a different level among the different brackets at T1 (p = 0.025), the highest level in the Gemini™ bracket when compared to the SmartClip™ bracket (p = 0.043). P. ginigvalis levels increased in the In-Ovation®R (p = 0.028) at T1. The subgingival levels of bacterial species associated with periodontal disease P. ginigvalis increased in the self-ligating brackets In-Ovation®R.Clinical Relevance: Some kinds of brackets could provide more retentive sites than others, and it seems to modulate the subgingival microbiota, since, in this study, we could observe the increase of the species associated with periodontal disease. Preventive protocols should be adopted in the use of self-ligating brackets.
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Soportes Ortodóncicos , Enfermedades Periodontales , Aggregatibacter actinomycetemcomitans , Femenino , Líquido del Surco Gingival , Humanos , Masculino , Soportes Ortodóncicos/microbiología , Porphyromonas gingivalisRESUMEN
The oral cavity is one of the environments on the human body with the highest concentrations of microorganisms that coexist harmoniously and maintain homeostasis related to oral health. Several local factors can shift the microbiome to a pathogenic state of dysbiosis. Existing treatments for infections caused by changes in the oral cavity aim to control biofilm dysbiosis and restore microbial balance. Studies have used probiotics as treatments for oral diseases, due to their ability to reduce the pathogenicity of the microbiota and immunoinflammatory changes. This review investigates the role of the probiotic Bifidobacterium animalis subsp. lactis (B. lactis) HN019 in oral health, and its mechanism of action in pre-clinical and clinical studies. This probiotic strain is a lactic acid bacterium that is safe for human consumption. It mediates bacterial co-aggregation with pathogens and modulates the immune response. Studies using B. lactis HN019 in periodontitis and peri-implant mucositis have shown it to be a potential adjuvant treatment with beneficial microbiological and immunological effects. Studies evaluating its oral effects and mechanism of action show that this probiotic strain has the potential to be used in several dental applications because of its benefit to the host.
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Bifidobacterium animalis , Periodontitis , Probióticos , Bacterias , Biopelículas , Disbiosis/terapia , Humanos , Periodontitis/terapia , Probióticos/farmacologíaRESUMEN
BACKGROUND: Leukotriene B4 (LTB4) is a potent lipid mediator that stimulate the immune response. Because dental pulp inflammation and dentin repair are intrinsically related responses, the aim of this research was to investigate the potential of LTB4 in inducing differentiation of dental pulp stem cells. METHODS: Microspheres (MS) loaded with LTB4 were prepared using an oil emulsion solvent extraction evaporation process and sterility, characterization, efficiency of LTB4 encapsulation and in vitro LTB4 release assay were investigated. Mouse dental pulp stem cells (OD-21) were stimulated with soluble LTB4 or MS loaded with LTB4 (0.01 and 0.1 µM). Cytotoxicity and cell viability was determined by lactate dehydrogenase and methylthiazol tetrazolium assays. Gene expression were measured by quantitative reverse transcription polymerase chain reaction after 3, 6, 24, 48 and 72 h. Mineralized nodule formation was assessed after 28 days of OD-21 cell stimulation with LTB4 in mineralized media or not. Groups were compared using one-way ANOVA test followed by Dunnett's post-test (α = 0.05). RESULTS: Treatment with LTB4 or MS loaded with LTB4 (0.01 and 0.1 µm-µM) were not cytotoxic to OD-21 cells. Treatment with LTB4 modulated the expression of the Ibsp (integrin binding sialoprotein) and Runx2 (runt-related transcription factor 2) genes differently depending on the experimental period analyzed. Interestingly LTB4 loaded in microspheres (0.1 µM) allowed long term dental pulp cell differentiation and biomineralization. CONCLUSION: LTB4, soluble or loaded in MS, were not cytotoxic and modulated the expression of the Ibsp and Runx2 genes in cultured OD-21 cells. When LTB4 was incorporated into MS, odontoblast differentiation and mineralization was induced in long term culture.
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Pulpa Dental , Leucotrieno B4 , Animales , Biomineralización , Diferenciación Celular , Células Cultivadas , Proteínas de la Matriz Extracelular/genética , Humanos , Leucotrieno B4/metabolismo , Leucotrieno B4/farmacología , Ratones , Microesferas , Odontoblastos/metabolismo , Células Madre/metabolismoRESUMEN
OBJECTIVE: Identify the potential for and risk factors of SARS-CoV-2 vertical transmission. METHODS: Symptomatic pregnant women with COVID-19 diagnosis in whom PCR for SARS-CoV-2 was performed at delivery using maternal serum and at least one of the biological samples: cord blood (CB), amniotic fluid (AF), colostrum and/or oropharyngeal swab (OPS) of the neonate. The association of parameters with maternal, AF and/or CB positivity and the influence of SARS-CoV-2 positivity in AF and/or CB on neonatal outcomes were investigated. RESULTS: Overall 73.4% (80/109) were admitted in hospital due to COVID-19, 22.9% needed intensive care and there were four maternal deaths. Positive RT-PCR for SARS-CoV-2 was observed in 14.7% of maternal blood, 13.9% of AF, 6.7% of CB, 2.1% of colostrum and 3.7% of OPS samples. The interval between COVID-19 symptoms and delivery was inversely associated with SARS-CoV-2 positivity in the maternal blood (p = 0.002) and in the AF and/or CB (p = 0.049). Maternal viremia was associated with positivity for SARS-CoV-2 in AF and/or CB (p = 0.001). SARS-CoV-2 positivity in the compartments was not associated with neonatal outcomes. CONCLUSION: Vertical transmission is possible in pregnant women with COVID-19 and a shorter interval between maternal symptoms and delivery is an influencing factor.
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COVID-19/transmisión , Transmisión Vertical de Enfermedad Infecciosa/estadística & datos numéricos , Complicaciones Infecciosas del Embarazo/virología , SARS-CoV-2/aislamiento & purificación , Adulto , Líquido Amniótico/virología , Brasil/epidemiología , COVID-19/mortalidad , COVID-19/virología , Calostro/virología , Femenino , Humanos , Recién Nacido , Masculino , Embarazo , Complicaciones Infecciosas del Embarazo/mortalidad , Estudios Prospectivos , Adulto JovenRESUMEN
OBJECTIVES: The aim of this study was to investigate the inflammatory infiltrate, osteoclast formation, and expression of MMP-9 during the healing phase following root canal treatment in teeth with apical periodontitis. MATERIALS AND METHODS: Apical periodontitis was induced in dogs teeth, and root canal treatment was performed in a single visit or using calcium hydroxide as intracanal medication. One hundred and eighty days following treatment the presence of inflammation was examined, and the tissues were stained to detect osteoclasts by means of a tartrate resistant alkaline phosphatase (TRAP) assay. Synthesis of MMP-9 was detected using Western blotting and immunohistochemistry. RESULTS: Teeth with apical periodontitis that had root canal therapy performed in a single visit presented a higher synthesis of MMP-9 compared with root canal treatment using calcium hydroxide. Treatment with calcium hydroxide resulted in a reduced amount of inflammatory cells and MMP-9 positive cells. Osteoclast formation, the number of MMP-9 positive osteoclasts and cementocytes, was reduced following root canal treatment, regardless of the root canal treatment protocol used. CONCLUSION: Root canal treatment reduced the amount of inflammatory cells and osteoclasts in periapical area. The use of calcium hydroxide as intracanal medication resulted in a lower synthesis of MMP-9, though the number of osteoclasts and MMP-9 positive osteoclasts were similar between the groups. CLINICAL RELEVANCE: Periapical bone repair following root canal treatment is impacted by therapy performed either in single visit or using calcium hydroxide dressing measured by inflammatory cell recruitment, osteoclast formation, and MMP-9 synthesis.
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Periodontitis Periapical , Materiales de Obturación del Conducto Radicular , Animales , Hidróxido de Calcio/farmacología , Cavidad Pulpar , Perros , Inflamación , Metaloproteinasa 9 de la Matriz , Osteoclastos , Periodontitis Periapical/tratamiento farmacológico , Irrigantes del Conducto Radicular , Tratamiento del Conducto RadicularRESUMEN
OBJECTIVES: To answer the questions: (1) Does reducing estrogen levels influence the microbial composition of the oral cavity? (2) Does the presence of periapical lesion (PL) cause changes in the oral microbiota? (3) Since estrogen deficiency alters the oral microbiota, can this be one of the factors that contribute to the increase of the PL? MATERIALS AND METHODS: Thirty-six rats were divided into four groups: sham (control), ovariectomy (OVX), control with PL (Sham + PL), and OVX + PL. After 9 weeks of OVX, the lower first molars were submitted to PL induction. After 21 days, the microbiological collection of the oral cavity was performed, and the animals were euthanized. The contents were evaluated by the checkerboard DNA-DNA hybridization method, to verify the prevalence of 40 bacterial species (divided into 7 microbial complexes). The blocks containing the lower first molars were submitted to histotechnical processing and staining with hematoxylin and eosin (HE), for the measurement of the periapical lesion area. The results were submitted to ANOVA and Kruskal-Wallis tests and Tukey and Dunn post-tests, with a significance level of 5%. RESULTS: In conditions of estrogen deficiency, there was alteration of the oral microbiota. The OVX groups had a higher amount of bacteria compared to the SHAM group in most of the microbial complexes (p < 0.001). The animals in the control group (with or without lesion) did not present a statistically significant difference (p > 0.001) in any of the microbial complexes. The PLs in OVX animals were significantly higher compared to SHAM animals (p < 0.001). CONCLUSIONS: Hypoestrogenicity conditions interfere in the oral microbiota by increasing the amount of bacteria in the saliva and influencing the progression of periapical lesions. CLINICAL RELEVANCE: This inedited study shows that deficiency of estrogen leads to alteration of the oral microbiota.
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Microbiota , Animales , Estrógenos , Femenino , Humanos , Diente Molar , Boca , Ovariectomía , Ratas , SalivaRESUMEN
OBJECTIVES: The objective of this study was to evaluate the effect of non-steroidal anti-inflammatory drugs (NSAIDs) in controlling pulpal and periapical inflammation in vivo as a potential coadjutant systemic therapy for pulpitis. MATERIALS AND METHODS: A suspension containing E. coli lipopolysaccharide (LPS; 1.0 µg/µL) was inoculated into the pulp chamber of the first molars of C57BL/6 mice (n = 72), and the animals were treated daily with indomethacin or celecoxib throughout the experimental periods. After 7, 14, 21, and 28 days, the tissues were removed for histopathological, histoenzymology, histometric, and immunohistochemical evaluation. RESULTS: Inoculation of LPS into the pulp chamber induced the synthesis of the enzyme cyclooxygenase-2 (COX-2) in dental pulp and periapical region. Indomethacin and celecoxib treatment changed the profile of inflammatory cells recruited to dental pulp and to the periapex, which was characterized by a higher mononuclear cell infiltrate, compared to LPS inoculation alone which recruited a higher amount of polymorphonuclear neutrophils. Administration of indomethacin for 28 days resulted in the development of apical periodontitis and increased osteoclast recruitment, unlike celecoxib. CONCLUSIONS: NSAIDs indomethacin and celecoxib changed the recruitment of inflammatory cells to a mononuclear profile upon inoculation of LPS into the pup chamber, but indomethacin enhanced periapical bone loss whereas celecoxib did not. CLINICAL RELEVANCE: Celecoxib, a selective COX-2 inhibitor, can change the profile of inflammatory cells recruited to the dental pulp challenged with LPS and might a be potential systemic coadjutant for treatment of pulpitis.
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Lipopolisacáridos , Preparaciones Farmacéuticas , Animales , Antiinflamatorios no Esteroideos/farmacología , Escherichia coli , Inflamación , Ratones , Ratones Endogámicos C57BLRESUMEN
OBJECTIVES: To evaluate denosumab, a human monoclonal antibody that mimics the effects of osteoprotegerin in bone metabolism, as a topical treatment of root surface to be used prior to delayed tooth replantation. MATERIALS AND METHODS: Thirty-six rats' right incisors were used. Teeth were extracted and divided into: delayed replantation without root surface treatment (control); delayed replantation with root surface treatment with denosumab 60 mg/mL and 30 mg/mL, respectively, for 10 min both experimentals groups. After that, the root canals were filled with calcium hydroxide and replanted. After 15 and 60 days, the animals were euthanized, and the samples were collected and processed for microscopic analysis. Histological sections were performed, and stained with HE to describe the dental characteristics, measure ankylosis, replacement resorption, and dental resorption by conventional microscopy. Also, was performed Brown & Brenn staining and immunohistochemistry for RANKL, OPG, and periostin. RESULTS: Denosumab 60 mg/mL reducted ankylosis (p < 0.0001), replacement resorption (p < 0.0001), and tooth resorption, 60 days after replantation, compared to untreated replanted teeth (p < 0.005). Lower bacterial contamination in root surface in the denosumab treatment groups was found, regardless of the concentration used (p < 0.001). Also, denosumab treatment inhibited the expression of RANKL without modulating OPG. Periostin was observed in periodontal ligament of replanted tooth, although this labelling was absent in the ankylosis areas, in both experimental periods. CONCLUSION: Treatment of the root surface with denosumab at 60 mg/mL of rat teeth before delayed replantation reduced dental root resorption compared with the untreated teeth after 60 days. CLINICAL RELEVANCE: Survival of a replanted tooth has been a challenge in clinical practice. The use of a medication, such as denosumab, to limit dental root resorption represents an important therapeutical approach.
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Resorción Radicular , Anquilosis del Diente , Animales , Incisivo , Ligamento Periodontal , Ratas , Resorción Radicular/prevención & control , Reimplante Dental , Raíz del DienteRESUMEN
OBJECTIVE: To verify the association between 25(OH)D level and polymorphisms in the vitamin D receptor gene (VDR) with the disturbance in the dental development and eruption. DESIGN: A total of 183 children from two datasets were evaluated. The first dataset was a case-control (15:15) designed to assess if persistent primary tooth (PPT) is associate with serum 25(OH)D level and with genetic polymorphisms in VDR. The second dataset of genomic DNA samples from 54 children with delayed tooth eruption (DTE) and 99 controls were analysed to verify if genetic polymorphisms in VDR (rs2228570 and rs739837) are associated with DTE. The 25(OH)D and the genotyping/allele distribution were analysed using the T-test and chi-square test, respectively. RESULTS: The level of 25(OH)D in the PPT group (24.9 ± 6.4 mg/mL) was significantly lower than the control (30.0 ± 7.0 mg/mL) (p=.047). Our data show that children with 25(OH)D deficiency are more likely to present PPT (OR = 2.36; 95%CI: 1.51, 3.70). The rs739837 and rs2228570 polymorphisms were not associated with DTE (OR = 1.44; 95%CI: 0.87, 2.39 and OR = 0.80; 95%CI: 0.45, 1.44, respectively). CONCLUSIONS: Vitamin D deficiency is a risk factor for PPT.
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Erupción Dental , Deficiencia de Vitamina D , Niño , Humanos , Polimorfismo Genético , Factores de Riesgo , Erupción Dental/genética , Diente PrimarioRESUMEN
INTRODUCTION: The objective of this study was to evaluate in vitro and in vivo bacterial endotoxin (LPS) adhesion in polyurethane and silicone esthetic elastomeric orthodontic ligatures. The null hypotheses tested were: (1) there is no LPS adhesion in esthetic elastomeric orthodontic ligatures; and (2) there is no difference in the LPS adhesion between different brands of these ligatures. METHODS: For the in vitro study, 4 types of esthetic elastomeric ligatures were used (Sani-Ties and Sili-Ties [Dentsply GAC, Islandia, NY;] and Mini Single Case Ligature Stick and Synergy low-friction ligatures [Rocky Mountain Orthodontics, Denver, Colo]), contaminated or not with endotoxin solution. Replicas of twisted wire and cast stainless steel ligatures were used as control. For the in vivo study, 10 male and 10 female patients, aged 15-30 years, received the same 4 types of ligatures, 1 of each inserted in the maxillary and mandibular canines, randomly. Twenty-one days later, the ligatures were removed, and endotoxin quantification was performed using the Limulus amebocyte lysate test. Data were analyzed (α = 0.05) using the Kruskal-Wallis test and Dunn's posttest or analysis of variance and Tukey's posttest. RESULTS: GAC silicone group had the lowest median contamination (1.15 endotoxin units/mL; P <0.0001) in vitro. In the in vivo study, the GAC silicone group had the lowest mean contamination (0.577 endotoxin units/mL; P <0.001). In both studies, the other groups did not present a significant difference when compared with each other (P >0.05). CONCLUSIONS: LPS exhibited an affinity for all the tested polyurethane and silicone elastomeric ligatures. GAC silicone ligatures presented with lower amounts of LPS attached to their surfaces. Thus, both null hypotheses were rejected.
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Soportes Ortodóncicos , Adolescente , Adulto , Elastómeros , Endotoxinas , Estética Dental , Femenino , Fricción , Humanos , Masculino , Ensayo de Materiales , Diseño de Aparato Ortodóncico , Alambres para Ortodoncia , Acero Inoxidable , Adulto JovenRESUMEN
Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia commonly affecting children with frequent somatic mutations in MAPK pathway genes including BRAFV600E and MAP2K1. Some studies suggest that LCH cells can recruit and modulate inflammatory cells, which could provide reciprocal survival signals. To characterize the immune profile of infiltrating inflammatory cells, and to clarify their participation in LCH pathogenesis, a detailed immunohistochemical analysis was performed. Fifteen (10 children, 5 adults) LCH cases were assessed through macrophage (CD68 and CD163), mature dendritic cell (mDC; CD83 and CD208), regulatory T cell (Treg; CD4, CD25 and FOXP3) and cytotoxic lymphocyte (CL; CD56, CD57, perforin and granzyme B) immunomarkers. Moreover, lymphocytic and LCH markers were also analysed. All cases were S100, CD1a, CD207 and CD4-positive. Bcl-2 and cyclin D1 expression was observed in 13 of 15 cases. In the immune microenvironment, M2-polarized macrophages and Tregs were the predominant cell populations, followed by significantly (P < .005) smaller levels of mDCs and CLs. Additionally, the number of CD3 + cells was significantly higher than that of CD20 + cells. In the CD3 + cell population, there were a significantly higher number of CD4 + cells than CD8 + cells. While there were no differences when comparing the paediatric and adult populations, FOXP3 + cells were significantly higher in patients with multisystem involvement and treated with chemotherapy, than single-site cases and those without chemotherapy. Our results suggest that M2-polarized macrophages and Treg infiltration can promote LCH development and survival, probably through pro-tumoral, immunosuppressive and/or cytokine-mediated mechanisms. This work highlights the need for further exploration of immune-targeted therapy for LCH.
Asunto(s)
Histiocitosis de Células de Langerhans/metabolismo , Células de Langerhans/fisiología , Macrófagos/metabolismo , Linfocitos T Reguladores/metabolismo , Adulto , Antígenos CD/metabolismo , Diferenciación Celular , Microambiente Celular , Niño , Preescolar , Citocinas/metabolismo , Células Dendríticas/metabolismo , Femenino , Factores de Transcripción Forkhead/metabolismo , Humanos , Inmunohistoquímica/métodos , Lactante , Macrófagos/inmunología , Masculino , Linfocitos T Citotóxicos/metabolismo , Linfocitos T Reguladores/inmunología , Células Th2/inmunologíaRESUMEN
OBJECTIVES: To evaluate the in vitro effects of radiotherapy (RT) on the morphological surface of the enamel and dentin and to determine the best adhesive system and most appropriate time to restore teeth in head and neck cancer patients. METHODS: Sixty third molars were cut into 120 enamel fragments and 120 dentin fragments and divided into four groups (n = 30): G1 (control): nonirradiated, only restorative procedure; G2: restorative procedure immediately before RT; G3: restorative procedure immediately after RT; and G4: restorative procedure 6 months after RT. Each group was divided into two subgroups: Adper™ Single Bond 2 (SB) and Clearfill SE Bond (CL) based on the material used. After RT and restorative procedures, the specimens were subjected to confocal microscopy and shear bond strength test. Data were analyzed using a two-way ANOVA followed by Tukey's test at a significance level of 5%. RESULTS: Morphological changes were observed in both substrates after a cumulative dose of 40 Gy, and after 60 Gy, the changes were more evident in both substrates. CL had the highest strength values in both substrates (p < 0.05), and G2 had the lowest strength values for the enamel and dentin (p < 0.05). CONCLUSIONS: Based on the in vitro study results, we can conclude that RT substantially changes the morphological surface of enamel and dentin and impairs the bond strength. The Clearfill system yielded better results than Adper Single Bond 2, and restoring teeth before RT resulted in the worst results in both substrates.
Asunto(s)
Adhesivos/efectos de la radiación , Esmalte Dental/efectos de la radiación , Recubrimientos Dentinarios/efectos de la radiación , Dentina/efectos de la radiación , Neoplasias de Cabeza y Cuello/radioterapia , Bisfenol A Glicidil Metacrilato/efectos de la radiación , Resinas Compuestas/efectos de la radiación , Recubrimiento Dental Adhesivo , Dentición Permanente , Neoplasias de Cabeza y Cuello/patología , Humanos , Ensayo de Materiales , Diente Molar/efectos de la radiación , Dosis de Radiación , Distribución Aleatoria , Cementos de Resina/efectos de la radiación , Resistencia al Corte/efectos de la radiación , Fracturas de los Dientes/etiología , Fracturas de los Dientes/patologíaRESUMEN
AIM: To assess the efficacy of treatment using a minimally invasive approach (selective removal of carious tissue, restoration and preventive strategies) in immature permanent molars with MIH. DESIGN: A total of 281 patients, aged 6-8 years, with carious lesions (ICDAS 5-6), severe MIH, and incomplete root formation (one tooth/patient) were included. After clinical and radiographic examinations, selective carious tissue removal was performed, and the teeth received interim restoration for 6 months and were then restored with composite resin. Clinical and radiographic follow-up was undertaken, 6, 12, 18, and 24 months. A protocol of preventive oral care measures was established and repeated at each follow-up, including diet counselling, oral hygiene instruction, dental plaque control, and topical application of fluoride varnish containing CPP-ACP. All clinical procedures and evaluations were done by a single operator. RESULTS: Clinical and radiographic success was observed 24 months after treatment in 96.8% of the cases. Failures were due to enamel fracture at restoration margins, resulting in pulpitis and absence of apex closure. CONCLUSION: Selective removal of carious tissue, interim, and subsequently definitive restoration, combined with home and professional preventive measures, maintained marginal integrity of restorations in immature permanent molars with severe MIH, confirmed by pulp vitality and occurrence of apexogenesis.