Evaluation of the presence of gingivitis as confounding factor in assessing inflammatory status in serum and saliva of dogs with diabetes mellitus.

The aim of this study was to evaluate the changes in the serum and salivary inflammatory markers induced by Diabetes mellitus (DM) in dogs and to assess the possible confounding effect of gingivitis. A panel of 13 cytokines was measured in the serum and saliva of dogs diagnosed with DM and compared with healthy dogs without gingivitis (control group 1; CG1) and dogs with gingivitis but otherwise healthy (control group 2; CG2). The results of the present study showed statistically significantly higher levels of IL-8, KC-like and MCP1 in the serum of dogs with DM compared to CG1 dogs. In the case of saliva, the DM group presented statistically higher GM-CSF, IL6, IL15, and MCP1 levels compared to CG1, and lower KC-like chemokine compared to CG2. Finally, gingivitis produced changes in saliva, with salivary levels of GM-CSF, IL-6, IL-7, IL-15, IP-10, KC-like, IL-10, IL-18, MCP1, TNFα being statistically significantly higher in the saliva of CG2 dogs compared to CG1. The results of the present study indicate that dogs with DM have altered cytokine levels in serum and saliva compared to healthy dogs. In addition, this study highlights the importance of taking oral health into account when determining cytokines in dogs, as gingivitis can significantly alter their concentrations. .

Potential role of salivary vitamin D antimicrobial peptide LL-37 and interleukins in severity of dental caries: an exvivo study.

INTRODUCTION: Vitamin D performs various functions as a hormone by promoting calcium absorption but plays a major role in innate immunity,cell differentiation, cell maturation through its genomic effects via vitamin D receptor. The immune response also plays a major role in tooth surface and supporting structure destruction and playing a major factor in high caries formation. The inflammatory cytokines are released has proinflammatory cytokines and stimulate cells in disease process. Therefore, in the present study we have evaluated the association of salivary vitamin D, LL-37, interleukins 6 and 17A in various levels of severity of dental caries. METHOD: Ethical approval was obtained (NU/CEC/2020/0339), 377 individuals reporting to department of conservative dentistry and endodontics, AB Shetty memorial institute of dental sciences were included based on inclusion criteria. The individuals were further divided into caries free(N = 105) and caries active(N = 272) based on their caries prevalence. The salivary were collected and evaluated for vitamin D, LL-37,IL-17A and IL-6.Results were statistically analysed with SPSS vs 22 (IBM Corp, USA). Normally distributed data were expressed as mean ± SD. Skewed data were expressed as median and interquartile range. To compare (mean) outcome measures between the two groups unpaired independent t-test was applied and for values in median IQR, Mann Whitney U test was used. All statistical analysis for P value were two-sided and significance was set to P ≤ 0.05. RESULTS: The study showed that, the salivary vitamin D statistically decreased with increasing severity of caries which showed that vitamin D plays an important role in prevention of caries. Antimicrobial peptide LL-37 was higher in caries free group but was not statistically significant, salivary IL-6 level was higher in caries active group but intergroup comparison did not show significant difference. Salivary IL-17A did not show statistically significant between caries active and caries free group. CONCLUSION: The salivary levels of vitamin D may play a vital role in prevalence of dental caries and its severity which can be a underlying cause in presence of other etiological factors.

Salivary levels of catalase, total antioxidant capacity and interleukin-1ß and oral health-related quality of life after matcha and green tea consumption for patients with gingivitis: A randomized clinical trial.

OBJECTIVES: To evaluate the changes in salivary levels of catalase (CAT), total antioxidant capacity (TAC) and IL-1ß (primary outcomes) as well as gingival health and oral health-related quality of life (OHRQOL) 1 month after the consumption of matcha and green tea in adult patients with gingivitis. METHODS: This study was a parallel randomized clinical trial. Forty gingivitis adult patients were randomly assigned to drink either matcha or green tea cup twice daily for a duration of 1 month. They were asked to keep their habitual oral hygiene measures. Plaque index (PI) and bleeding on probing (BOP) were recorded. In addition, saliva was collected at baseline and 1 month after tea consumption. Salivary levels of CAT, TAC and IL-1ß were determined by ELISA. Each participant was asked to fill OHIP-14 questionnaire before and after tea consumption. RESULTS: Following tea intake, 40.6% of the study sample had healthy gingiva. Both groups similarly showed reductions in PI (0.32 ± 0.11-0.22 ± 0.08) and BOP (0.24 ± 0.08-0.13 ± 0.07) scores after tea consumption. There was a significant difference between mean TAC before and after matcha tea consumption only. Non-significant reductions in salivary levels of CAT and IL-1ß were detected after tea consumption. OHRQOL of participants was improved after tea, both types, consumption. CONCLUSION: Despite study limitations, daily consumption of matcha and green tea might be beneficial as they potentially enhance OHRQOL of individuals with gingivitis and reduce the extent of gingivitis despite non-significant changes in salivary antioxidants and IL-1ß levels.

[Shaping approaches to standardization of oropharynx mucous membrane assessment of immunological parameters]. / Formirovanie podkhodov k standartizatsii issledovaniya immunologicheskikh parametrov slizistoi obolochki rotoglotki.

Basis of acute pharyngitis pathogenesis is an inflammatory process at the entrance gate of the infection. Therefore, local immunity study proves to be the most informative. Difficulty in making that type of assessment is lack of generally accepted reference values and biological sampling techniques. OBJECTIVE: Validation of biological sampling techniques to study the parameters of local mucosal immunity in oropharynx acute inflammatory diseases. MATERIAL AND METHODS: 30 people with acute catarrhal pharyngitis with intoxication syndrome were examined. The sampling was carried out in 7 different ways. 1. Collect saliva samples using the passive drool collection method. 2. Collect saliva, using cotton swabs placed into the mouth for 3 minutes. 3. Cotton swabs wrapped around a metal probe was placed on palatine tonsils and lateral walls of the oropharynx. 4. Instead of a cotton swab, a disc of laboratory filter paper with a diameter of 0.7 cm was used. 5. Scrape by the mucous membrane of the palatine tonsils and lateral walls of the oropharynx were made with a cytobrush. 6. Using a cytobrush, scrapings were made from the mucous membrane of only the posterior pharyngeal wall, excluding the region of the palatine tonsils. 7. Using a cytobrush to make scrapings from the only palatine tonsils mucous membrane. RT-PCR was used to determine IL-1ß mRNA. RESULTS: Minimal IL-1ß mRNA values were detected in saliva collected by passive flow (0.095 [0; 3.45] units) and on a cotton swab (0.21 [0.1; 3.82] units). IL-1ß mRNA in the material collected by methods No. 3 and No. 4 on a cotton swab and a paper disk did not differ significantly from each other. Its level was higher than in saliva and lower than in scrapings. The maximum result was revealed with method No. 5 when simultaneously taking scrapings from the palatine tonsils and posterior pharyngeal wall mucous membrane (4.76 [0.92; 8.13] units). The expression of IL-1ß mRNA in the material obtained by methods No. 6 and No. 7 did not differ significantly from each other. CONCLUSION: Separated scrapings collecting from the palatine tonsils or posterior pharyngeal wall mucous membrane will allow assessing the inflammatory response autonomously in the lymphoid tissue and separately on the mucosa of the posterior pharyngeal wall. The mucosal scraping technique was the most effective for assessing cytokines in the oropharyngeal mucosal membrane.

Effect of scaling on levels of interleukin 1-beta and clinical periodontal parameters among e-cigarette users and non-smokers: A prospective study.

INTRODUCTION: This cohort study aimed to compare the effect of ultrasonic scaling on the expression of IL-1ß in the gingival crevicular fluid (GCF) among ENDS users and non-smokers (NS) with gingivitis. METHODS: Self-reported current electronic nicotine delivery system (ENDS) users and NS with generalized gingivitis were included in this study. All the patients underwent scaling at the baseline visit (T0). Clinical measures, periodontal parameters [probing depth (PD), plaque index (PI), and bleeding on probing (BOP)], and GCF IL-1ß were measured at T0, after 1 week (T1) and after 3 weeks (T2). Wilcoxon signed rank test was used to assess the changes in the periodontal measurements and IL-1ß levels at different time points and Mann-Whitney U Test was used to compare the two groups. RESULTS: A total of 38 individuals (18 NS and 20 ENDS users) participated in the study. The PD was significantly higher in ENDS users than in NS at baseline. However, the PI and BOP were similar in all groups at baseline. At T1, the PI was significantly lower for NS than for ENDS users (p=0.045). At T2, there were no significant differences in any of the parameters assessed between the two groups. For ENDS users, BOP was significantly lower at T1 than at baseline. For NS, the BOP at T1 and T2 and the PI at T1 were significantly lower than at baseline. There was no difference in the GCF IL-1ß levels in NS and ENDS users at baseline, T1, and T2. At T2, there was a significant reduction in IL-1ß (p<0.05) than at baseline in both groups. CONCLUSIONS: Both ENDS users and NS with gingivitis responded similarly to scaling. GCF IL-1ß levels were significantly higher at baseline (p<0.05) compared with their levels at T1 and T2 for both the groups. CLINICAL TRIAL REGISTRATION: The study was registered on the official website of ClinicalTrials.gov. IDENTIFIER: ID NCT05745324.

Mines of cytokine: A treasure trove in pulpal and periapical diseases.

Pulpitis is a special disease of dental pulp. It causes localized inflammation, due to various inflammatory mediators such as cytokines and chemokines. These inflammatory mediators are responsible for various reparative and resorptive processes in the dental pulp. The balance between these processes ultimately determines the viability of the tooth. Due to the important properties of various inflammatory markers, the correlation of cytokinin gene expression in various stages of inflammation becomes necessary to focus on. Several studies in the past have focused on the importance of such correlation to help in diagnostic applications. The nature of these inflammatory mediators can help us in diagnostic evaluation. Several attempts have been made to focus on these associations so that it can assist in making clinical decisions effectively. The data available are vast but are the most neglected topic. This review article briefly outlines and summarizes the importance of various inflammatory mediators such as cytokinin and chemokines in various pathways of pulpal and periapical inflammation in explanatory and diagrammatic forms. Knowledge gained about pulpal inflammatory response may aid in understanding the molecular level of inflammatory pulpal and periapical diseases, which shall modify our future diagnostic modalities. Several medicaments are used in the treatment of minimal to advanced dental caries which leads to periapical infections. Thorough understanding of these medicaments can resolve secondary infection and can improve the prognosis of the treated tooth.

Association of genetic polymorphism of interleukin 1-alpha and interleukin 1-beta with external apical root resorption in orthodontic patients.

OBJECTIVE: To assess the allele rs 1143634 in IL-1ß and rs1800587 in IL-1α in patients for orthodontically induced external apical root resorption (EARR). MATERIAL AND METHODS: Intra-oral periapical radiograph (IOPA) of maxillary incisors of 142 Patients were evaluated for resorption at two time points; before the start of fixed mechanotherapy (T1) and after one year of treatment (T2). The individuals with root resorption<2mm were categorized as a control group (group 1; n=90), and resorption>2mm were categorized as case group (group 2; n=52). Buccal swabs of all patients were taken and DNA could be isolated in 95 out of 142 samples (group 1 {n=58}, group 2 {n=37}), which were then screened for the selected two polymorphic targets to determine the nucleotide status of these targets. Tetra-primer ARMS PCR reactions were carried out using all 4 primers for each polymorphism. RESULTS: rs11800587 was not associated with risk of EARR in any inheritance model. Chi-square test for association of alleles with EARR revealed that rs1143634 was associated with the risk of EARR in an allelic model in such a way that A allele of this SNP increased the risk of EARR 4 folds [OR=4.375; P=0.016]. However, the adjusted level of significance using the Holm-Bonferroni method for rs1143634 was P<0.010 for A and G comparison rendering the results non-significant. CONCLUSION: SNP rs1143634 and SNP rs11800587 were not associated with risk of EARR in any inheritance model.

Er:YAG laser suppresses pro-inflammatory cytokines expression and inflammasome in human periodontal ligament fibroblasts with Porphyromonas gingivalis-lipopolysaccharide stimulation.

Background/purpose: Periodontitis is an inflammatory condition of the tooth-supporting structures triggered by the host's immune response towards the bacterial deposits around the teeth. It is well acknowledged that pro-inflammatory interleukin (IL)-6, IL-8, MCP-1 as well as the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, are the key modulators in the activation of this response. Erbium-doped yttrium-aluminium-garnet (Er:YAG) laser, a solid-state crystal laser have been commonly used in the treatment of periodontal diseases. However, little is understood about the molecular mechanism of the Er:YAG laser, especially in targeting the host immune response brought on by periodontal pathogens. Hence, the current study focused on the protective effects of Er:YAG laser on periodontitis in-vitro in terms of pro-inflammatory cytokines, chemokines and NLRP3 inflammasome expressions. Materials and methods: Human periodontal ligament fibroblast (PDLFs) were first stimulated with lipopolysaccharides (LPS) from P. gingivalis (Pg-LPS) to simulate periodontitis. Cells were then irradiated with Er:YAG laser of ascending energy densities (3.6-6.3 J/cm2), followed by cell proliferation and wound healing assay. Next, the effects of Er:YAG laser on the expressions of IL-6, IL-8, MCP-1, NLRP3, and cleaved GSDMD were examined. Results: Pg-LPS was found to reduce cell's proliferation rate and wound healing ability in PDLFs and these were rescued by Er:YAG laser irradiation. In addition, LPS stimuli resulted in a marked upregulation in the secretion of IL-6, IL-8 and MCP-1 as well as the mRNA and protein expression of NLRP3 and cleaved-GSDMD protein whereas Er:YAG laser suppressed the elicited phenomena. Conclusion: To our knowledge, this is the first study to look into the laser's implication on the NLRP3 inflammasome in periodontitis models. Our study reveals a crucial role of Er:YAG laser in ameliorating periodontitis in-vitro through the modulation of IL-6, IL-8, MCP-1 and the NLRP3 inflammasome and highlights that the control of the NLRP3 inflammasome may become a potential approach for periodontitis.

Burning Mouth Syndrome Treated with Low-Level Laser and Clonazepam: A Randomized, Single-Blind Clinical Trial.

OBJECTIVE: Burning mouth syndrome (BMS) is a chronic pain disorder characterized by intraoral burning or dysaesthetic sensation, with the absence of any identifiable lesions. Numerous treatments for BMS have been investigated, though without conclusive results. An analysis was conducted of the efficacy of treatment with a low-level diode laser and clonazepam in patients with BMS, and a study was carried out on the levels of different salivary biomarkers before and after treatment. MATERIAL AND METHODS: A randomized, single-blind clinical trial was carried out involving 89 patients divided into the following groups: group 1 (laser, The Helbo® Theralite Laser 3D Pocket Probe + clonazepam) (n = 20), group 2 (sham laser placebo) (n = 19), group 3 (laser) (n = 21) and group 4 (clonazepam) (n = 18). Symptom intensity was scored based on a visual analogue scale (VAS). Sialometry was performed before and after treatment, and the Xerostomia Inventory, Oral Health Impact Profile-14 (OHIP-14) and Mini-Nutritional Assessment (MNA) questionnaires were administered. The following markers were measured in saliva samples: interleukins (IL2, IL4, IL5, IL6, IL7, IL8, IL1ß, IL10, IL12, IL13, IL17, IL21 and IL23), proteins (MIP-3α, MIP-1α and MIP-1ß), GM-CSF, interferon gamma (IFNγ), interferon-inducible T-cell alpha chemoattractant (ITAC), fractalkine and tumor necrosis factor α (TNFα). RESULTS: A significant decrease in the VAS scores was observed after treatment in group 1 (laser + clonazepam) (p = 0.029) and group 3 (laser) (p = 0.005). In turn, group 3 (laser) showed a decrease in the salivary concentration of fractalkine (p = 0.025); interleukins IL12 (p = 0.048), IL17 (p = 0.020), IL21 (p = 0.008), IL7 (p = 0.001) and IL8 (p = 0.007); proteins MIP1α (p = 0.048) and MIP1ß (p = 0.047); and TNFα (p = 0.047) versus baseline. Following treatment, group 1 (laser + clonazepam) showed significant differences in IL21 (p = 0.045) and IL7 (p = 0.009) versus baseline, while group 4 (clonazepam) showed significant differences in IL13 (p = 0.036), IL2 (p = 0.020) and IL4 (p = 0.001). No significant differences were recorded in group 2 (sham laser placebo). CONCLUSIONS: The low-level diode laser is a good treatment option in BMS, resulting in a decrease in patient symptoms and in salivary biomarkers. However, standardization of the intervention protocols and laser intensity parameters is needed in order to draw more firm conclusions.

Expression of IL-1ß, IL-6, TNF-α, and a-MMP-8 in sites with healthy conditions and with periodontal and peri-implant diseases: A case-control study.

Background: This study evaluated the gingival crevicular fluid (GCF) and Peri- implant crevicular fluid (PICF) concentrations of interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and active metalloproteinase-8 (a-MMP-8) in sites with healthy conditions vs. sites affected by periodontitis (PER) and peri-implantitis (PIM). Methods: Periodontally healthy (PH) sites with PER, sites with peri-implant health (PIH), and sites with PIM were investigated intra-individually, according to the inclusion criteria of each group. Probing pocket depth (PPD), plaque index, gingival index, and the presence or absence of bleeding on probing (BoP) were evaluated. In GCF and PICF samples, IL-1ß, IL-6, and TNF-α were quantified by ELISA Duoset® kit in combination with Ultramark® micro-ELISA digital reader; a-MMP8 concentration was analyzed by a chairside test (Perio/ImplantSafe®) in combination with a digital reader (ORALyzer®). Results: The concentrations of IL-6 and IL-1ß, TNF-α, and a-MMP-8 were significantly higher in the PIM and PER sites compared to healthy sites (P<0.05). Significantly higher concentrations of IL-1ß and a-MMP-8 were found in PIM vs. PER sites (P<0.05), while the concentrations of IL-6 and TNF-α did not differ between the PIM and PER groups (P>0.05). Conclusion: aMMP-8, IL-6, IL-1ß, and TNF-α presented higher GCF/PICF concentrations in diseased periodontal and peri-implant sites. However, only the concentrations of IL-1ß and a-MMP-8 were significantly higher in PIM than in PER sites.

Epithelial responses and Candida albicans pathogenicity are enhanced in the presence of oral streptococci

Abstract Experimental models that consider host-pathogen interactions are relevant for improving knowledge about oral candidiasis. The aim of this study was to assess the epithelial immune responses, Candida penetration of cell monolayers, and virulence during mixed species culture infections. Single species cultures of Candida albicans and mixed cultures (C. albicans, Streptococcus mutans, and Streptococcus sanguinis) were used to infect monolayers of HaCaT and FaDu ATCC HTB-43 cells for 12 h. After infection, IL-18 and IL-34 gene expression was measured to assess epithelial cell immune responses, and lactate dehydrogenase (LDH) activity was measured as an indicator of cell damage. Microscopy determined C. albicans morphology and penetration of fungal cells through the keratinocyte monolayer. Monolayers devoid of infection served as controls. Data were analyzed by an ANOVA one-way test followed by Tukey's post-hoc test (α = 0.05). The results found that IL-18 and IL-34 gene expression and LDH activity were significantly (p < 0.05) upregulated for both cell lines exposed to mixed species cultures compared with C. albicans alone. Candida albicans yeast and hyphae were evident in C. albicans only infections. In contrast, monolayers infected by C. albicans, S. mutans, and S. sanguinis exhibited higher microbial invasion with several hyphal aggregates detected. The presence of streptococci in C. albicans infection enhances the virulence and pathogenicity of the fungus with associated increased immune responses and tissue damage. Extrapolation of these findings to oral infection would indicate the added potential benefit of managing bacterial components of biofilms during treatment.

Resumo O objetivo deste estudo foi avaliar a resposta epithelial imune, a colonização da Candida albicans em monocamadas celulares e sua virulência em resposta a infecções de culturas de biofilme multiespécie. Culturas de biofilme monoespécie de C. albicans e culturas mistas (C. albicans, Streptococcus mutans e Streptococcus sanguinis) foram utilizadas para infectar monocamadas de células HaCaT e FaDu por 12 h. Após a infecção, a expressão dos genes IL-18 e IL-34 foi medida para avaliar as respostas imunes das células epiteliais. A atividade da lactato desidrogenase (LDH) foi medida como um indicador de dano celular. A microscopia determinou a morfologia de C. albicans e a penetração das células fúngicas através da monocamada de queratinócitos. Monocamadas em que não houve infecção serviram como controles. Os dados foram analisados por um teste ANOVA one-way seguido pelo teste post-hoc de Tukey (α = 0,05). Os resultados demonstraram que a expressão gênica de IL-18 e IL-34 e a atividade de LDH foram (p < 0,05) reguladas positivamente para ambas as linhagens de células expostas a culturas de espécies mistas em comparação com C. albicans isoladamente. Leveduras de C.albicans e hifas foram evidentes em infecções apenas por C. albicans. Entretanto, monocamadas infectadas por C. albicans, S. mutans e S. sanguinis exibiram maior invasão microbiana com vários agregados de hifas detectados. Dessa maneira, a presença de estreptococos na infecção por C. albicans aumentou a virulência e a patogenicidade do fungo com respostas imunes aumentadas associadas a danos nos tecidos. A extrapolação desses achados para a infecção oral indicaria o potencial benéfico do controle dos componentes bacterianos em biofilmes durante a terapia da candidíase

Insights on the role of cytokines in carious lesions / Insights sobre o papel das citocinas em lesões cariosas

Objetivo: A resposta imune da dentina-polpa à patogênese da cárie ainda é pouco compreendida devido à complexa interação dos processos envolvidos. O objetivo desta revisão foi explorar o papel das citocinas e sua relevância na patogênese da cárie dental. Resultados: A cárie dentária pode resultar em uma resposta inflamatória do hospedeiro na polpa dental, caracterizada pelo acúmulo de células inflamatórias levando à liberação de citocinas inflamatórias como, Interleucina-4 (IL-4), Interleucina (IL-6), Interleucina-8 (IL-8) e fator de necrose tumoral­α(TNF-α). IL-4 parece estar correlacionada com a profundidade das lesões cariosas; IL-6 está fortemente correlacionada com a doença cárie e é considerada um potente biomarcador; IL-8 pode ser um potente biomarcador tanto para cárie quanto para outras alterações presentes na polpa e sua liberação está correlacionada com TNF-α e IL-6; TNF-α desempenha um papel importante não apenas na progressão da cárie, mas também em outros processos patológicos. Conclusao: Mediadores específicos têm um grande potencial para servir como biomarcadores quanto à presença e progressão da doença cárie, o que incita a necessidade de mais investigações nesse campo (AU).

Objectives: The dentin-pulp immune response to caries pathogenesis is still poorly understood due to the complex interplay of the involving processes. The aim of this review was to explore the role of cytokines and its relevance in the pathogenesis of dental caries. Results: Dental caries can result in a host inflammatory response in the dental pulp, characterized by the accumulation of inflammatory cells leading to the release of inflammatory cytokines such as Interleukin-4 (IL-4), Interleukin (IL-6), Interleukin-8 (IL-8) and Tumor necrosis factor­ α (TNF- α ). IL-4 seems to be correlated to the depth of carious lesions; IL-6 is strongly correlated to caries disease and is considered a potent biomarker; IL-8 can be a potent biomarker for both caries and other changes present in the pulp and, its release is correlated to TNF- α and IL-6; TNF-α plays an important role not only in caries progression, but also in other pathological processes. Conclusion: Specific mediators have a great potential to serve as biomarkers alluding to the presence and progress of caries disease, urging further investigations in the field (AU)

Granulocyte-macrophage colony-stimulating factor (GM-CSF) in subjects with different stages of periodontitis according to the new classification

Abstract Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a multifunctional cytokine that regulates inflammatory responses in various autoimmune and inflammatory disorders. Objective: The purpose of this study was to analyze the gingival crevicular fluid (GCF) for GM-CSF, interleukin-1 beta (IL-1β), and macrophage inflammatory protein-1 alpha (MIP-1α) levels in patients with stage I, stage II, stage III, and stage IV periodontitis (SI-P, SII-P, SIII-P, and SIV-P). Methodology: A total of 126 individuals were recruited for this study, including 21 periodontal healthy (PH), 21 gingivitis (G), 21 SI-P, 21 SII-P, 21 SIII-P, and 21 SIV-P patients. Plaque index (PI), gingival index (GI), presence of bleeding on probing (BOP), probing depth (PD), and attachment loss (AL) were used during the clinical periodontal assessment. GCF samples were obtained and analyzed by an enzyme-linked immunosorbent assay (ELISA). Results: GCF GM-CSF, MIP-1α, and IL-1β were significantly higher in SII-P and SIII-P groups than in PH, G, and SI-P groups (p<0.05). There was no significant difference among the PH, G, and SI-P groups in IL-1β, GM-CSF, and MIP-1α levels (p>0.05). Conclusions: These results show that GM-CSF expression was increased in SII-P, SIII-P, and SIV-P. Furthermore, GM-CSF levels may have some potential to discriminate between early and advanced stages of periodontitis.

Efectos de la terapia periodontal no quirúrgica sobre el control glucémico de la Diabetes Mellitus Tipo 2: Revisión de literatura / Effects of non-surgical periodontal therapy on glycemic control of Type 2 Diabetes Mellitus: A literature review

Resumen Objetivo: Conocer la relación entre la enfermedad periodontal y la diabetes mellitus tipo 2, en el control de la glucemia. Diseño y métodos de investigación: Se realizó una búsqueda bibliográfica utilizando una base de datos (PubMed) con restricción del idioma inglés, buscando las investigaciones más recientes y con el mayor número de sujetos de investigación. Resultados: Los artículos revisados coinciden en que el tratamiento de la enfermedad periodontal mejora el control glucémico en pacientes con diabetes mellitus tipo 2, con una disminución promedio de 0,69% en el nivel de hemoglobina glucosilada (HbA1c). Conclusiones: El tratamiento periodontal mejora el control de la glucemia en pacientes con Diabetes Mellitus Tipo 2, debido a que disminuye el estado de inflamación sistémica y por lo tanto, también la cantidad de células inflamatorias (como IL6 y TNF- α) que provocan alteraciones en la actividad de la insulina.

Abstract Objective: To know the relationship between periodontal disease and type 2 diabetes mellitus in the control of blood glucose. Design and research methods: A bibliographic search was conducted using a database (PubMed) with english language restriction, looking for the most recent research and with the largest number of research subjects. Results: The articles reviewed coincide in the treatment of periodontal disease improves glycemic control in patients with diabetes mellitus type 2, with an average of 0.69% in the level of glycosylated hemoglobin (HbA1c). Conclusions: Periodontal treatment improves glycemic control in patients with Type 2 Diabetes Mellitus, as well as the number of inflammatory cells (such as IL6 and TNF-α) that cause alterations in insulin activity.

Periodontal disease and inflammatory blood cytokines in patients with stable coronary artery disease

ABSTRACT Periodontal disease has been associated with elevations of blood cytokines involved in atherosclerosis in systemically healthy individuals, but little is known about this association in stable cardiovascular patients. The aim of this study was to assess the association between periodontal disease (exposure) and blood cytokine levels (outcomes) in a target population of patients with stable coronary artery disease (CAD). Material and Methods This cross-sectional study included 91 patients with stable CAD who had been under optimized cardiovascular care. Blood levels of IL-1β, IL-6, IL-8, IL-10, IFN-γ, and TNF-α were measured by Luminex technology. A full-mouth periodontal examination was conducted to record probing depth (PD) and clinical attachment (CA) loss. Multiple linear regression models, adjusting for gender, body mass index, oral hypoglycemic drugs, smoking, and occurre:nce of acute myocardial infarction were applied. Results CAD patients that experienced major events had higher concentrations of IFN-γ (median: 5.05 pg/mL vs. 3.01 pg/mL; p=0.01), IL-10 (median: 2.33 pg/mL vs. 1.01 pg/mL; p=0.03), and TNF-α (median: 9.17 pg/mL vs. 7.47 pg/mL; p=0.02). Higher numbers of teeth with at least 6 mm of CA loss (R2=0.07) and PD (R2=0.06) were significantly associated with higher IFN-γ log concentrations. Mean CA loss (R2=0.05) and PD (R2=0.06) were significantly related to IL-10 concentrations. Elevated concentrations of TNF-α were associated with higher mean CA loss (R2=0.07). Conclusion Periodontal disease is associated with increased systemic inflammation in stable cardiovascular patients. These findings provide additional evidence supporting the idea that periodontal disease can be a prognostic factor in cardiovascular patients.

Association of Interleukin-17 polymorphism (-197G/A) in chronic and localized aggressive periodontitis

Abstract Interleukin 17(IL-17) is a pro-inflammatory cytokine produced mainly by Th17 cells. The present study was undertaken to investigate a possible association between IL-17 A genetic polymorphism at (-197A/G) and susceptibility to chronic and localized aggressive periodontitis (LAgP) in an Indian population. The study was carried out on 105 subjects, which included 35 LAgP patients, 35 chronic periodontitis patients and 35 healthy controls. Blood samples were drawn from the subjects and analyzed for IL-17 genetic polymorphism at (-197A/G), by using the polymerase chain reaction-restriction fragment length polymorphism method. A statistically significant difference was seen in the genotype distribution among chronic periodontitis patients, LAgP patients and healthy subjects. There was a significant difference in the distribution of alleles among chronic periodontitis patients, LAgP patients and healthy subjects. The odds ratio for A allele versus G allele was 5.1 between chronic periodontitis patients and healthy controls, and 5.1 between LAgp patients and healthy controls. Our study concluded that IL-17 A gene polymorphism at (-197A/G) is linked to chronic periodontitis and LAgP in Indian population. The presence of allele A in the IL-17 gene polymorphism (-197A/G) can be considered a risk factor for chronic periodontitis and LAgP.

Efeitos da colagem do esporão lingual no microambiente periodontal e liberação de subprodutos de materiais resinosos no tratamento de mordida aberta anterior em crianças / Effects of lingual sporing collage on the periodontal micro-environment and release of by-products of resin materials on the treatment of anterior open bite in children

Introdução: O aparelho ortodôntico passivo esporão é um método utilizado em crianças para correção de mordida aberta anterior. Para realizar a fixação desses acessórios dentes é necessário a utilização de materiais resinosos que podem liberar subprodutos tóxicos como BisGMA e TEGDMA. Além disso, a movimentação dentária ortodôntica pode aumentar a concentração de interleucinas no fluido crevicular gengival (FCG). A liberação de subprodutos resinosos no tratamento de mordida aberta e o comportamento da expressão de interleucinas ainda não estão elucidados na literatura. Objetivo: (1) avaliar a expressão de citocinas no FCG em crianças com mordida aberta que receberam fixação de esporão como tratamento e (2) quantificar o BisGMA e TEGDMA na saliva desses pacientes; e (3) avaliar a migração e viabilidade de quetarinócitos humanos expostos à resina. Métodos: Foram selecionados pacientes da clínica da FO-UFMG que apresentaram mordida aberta anterior. A colagem dos esporões foi realizada e os excessos de resina foram removidos. Foram realizados exames clínico e periodontal nos incisivos superiores e inferiores, coletas do FCG (antes da colagem ­ baseline, 24 h e 7 d após) e saliva (baseline, 30 min, 24 h e 7 d após a colagem). As citocinas do FCG foram analisadas por meio do BD™ Cytometric Bead Array e as amostras de saliva, através do método de cromatografia líquida de alta eficiência. Para as análises in vitro, células imortalizadas HaCat foram tratadas com meio de cultura condicionados com incrementos do sistema resinoso em 3 diferentes diluições e posteriormente foram realizados os testes de viabilidade e migração celular. Resultados: O estudo in vivo demonstrou que houve aumento do sangramento gengival nos incisivos inferiores após 7d quando comparados ao baseline e que este índice estava maior nos dentes inferiores do que nos superiores. Em 24h e 7d após a fixação do esporão, os níveis de IL-8 nos incisivos superiores estavam aumentados. Em 7d, a concentração de IL-1ß foi aumentada em comparação ao baseline nos dois grupos de dentes. Comparando os incisivos superiores e inferiores, os níveis de IL-8, IL-1ß e IL-6 foram maiores nos superiores às 24h. A produção de citocinas pôde ser positivamente correlacionada com o aumento do volume do FCG. Houve aumento dos níveis de BisGMA e TEGDMA na saliva em 30min, com redução dos níveis em 24h e 7d. Os resultados in vitro demonstraram aumento da migração celular nos queratinóscitos expostos aos meios condicionados mesmo em baixas concentrações .Conclusão: Foi identificado que após a colagem do esporão lingual ocorreu o aumento na expressão de interleucinas no FCG. Além disso, foi possível identificar a liberação de subprodutos resinosos na saliva das crianças. Embora os mesmos possam interferir na migração celular, não há estudos que quantifiquem a exposição mínima capaz de induzir alterações no indivíduo. Sendo assim, os benefícios da colagem do esporão sobrepõem seus efeitos adversos

Introduction: The passive spur orthodontic appliance is a method used in children to correct anterior open bite. To fix these teeth accessories, it is necessary to use resinous materials that can release toxic by-products such as BisGMA and TEGDMA. In addition, orthodontic tooth movement can increase the concentration of interleukins in the gingival crevicular fluid (FCG). The release of resinous by-products in the treatment of open bite and the behavior of interleukin expression are not yet elucidated in the literature. Objective: (1) to evaluate the expression of cytokines in the FCG in children with open bite who received spur fixation as treatment and (2) to quantify the BisGMA and TEGDMA in the saliva of these patients; and (3) evaluate the migration and viability of human ketarinocytes exposed to the resin. Methods: Patients from the FO-UFMG clinic who presented anterior open bite were selected. The spurs were bonded and the excess resin was removed. Clinical and periodontal examinations were performed on the upper and lower incisors, collections of the FCG (before bonding - baseline, 24 h and 7 d after) and saliva (baseline, 30 min, 24 h and 7 d after bonding). The FCG cytokines were analyzed using the BD ™ Cytometric Bead Array and the saliva samples, using the high performance liquid chromatography method. For in vitro analysis, immortalized HaCat cells were treated with culture medium conditioned with increments of the resin system in 3 different dilutions and then the viability and cell migration tests were performed. Results: The in vivo study showed that there was an increase in gingival bleeding in the lower incisors after 7d when compared to the baseline and that this index was higher in the lower than in the upper teeth. At 24h and 7d after spur fixation, IL-8 levels in the upper incisors were increased. At 7d, the concentration of IL-1ß was increased compared to the baseline in the two groups of teeth. Comparing the upper and lower incisors, the levels of IL-8, IL-1ß and IL-6 were higher in those above 24h. Cytokine production could be positively correlated with increased FCG volume. There was an increase in the levels of BisGMA and TEGDMA in saliva in 30 minutes, with a reduction in levels in 24h and 7d. The in vitro results demonstrated an increase in cell migration in keratinocytes exposed to conditioned media even in low concentrations. Conclusion: It was identified that after the gluing of the tongue spur there was an increase in the expression of interleukins in the FCG. In addition, it was possible to identify the release of resinous by-products in children's saliva. Although they can interfere with cell migration, there are no studies that quantify the minimum exposure capable of inducing changes in the individual. Therefore, the benefits of spur bonding override its adverse effects.

Liberação de componentes orgânicos e resposta periodontal em relação a um sistema restaurador resinoso Bulk-fill: estudo in vitro / Liberação de componentes orgânicos e resposta inflamatória frente a um sistema restaurador resinoso bulk-fill: estudo in vivo / Release Of Organic Components and Inflammatory Response to a Bulk-Fill Resin Results System: In Vivo Study

A maioria das resinas compostas apresenta metacrilatos como principais monômeros em sua composição. A liberação de monômeros de metacrilato, associada aos produtos de polimerização, tem sido considerada como fonte de uma série de reações biológicas como toxicidade ou reações pulpares. Os objetivos deste estudo foram avaliar o desempenho clínico de restaurações em LCNC com resina composta considerando-se também a presença de citocinas IL-1ß e IL-6 no fluido crevicular gengival e a liberação de componentes resinosos para a saliva. Utilizou-se o sistema restaurador FL-Bond II, (sistema adesivo) / Beautifil Bulk (resina composta restauradora). Foi feito um estudo clínico longitudinal in vivo, no qual foram selecionados pacientes que apresentavam uma lesão cervical não cariosa com necessidade restauradora. Dentes anteriores e posteriores com LCNC e sensibilidade foram designados como grupo experimental e o dente correspondente como grupo controle. Previamente ao tratamento, houve avaliação periodontal, coleta de saliva e de fluido crevicular gengival (FCG). As restaurações foram confeccionadas e, após 10 minutos, 7 dias, 1 mês e 6 meses foi realizada avaliação clínica das mesmas de acordo com o critério Federal Dentist International (FDI) e da resposta periodontal. Adicionalmente, em todos estes períodos de avaliação houve coleta de saliva e de fluido crevicular. As amostras de saliva foram analisadas por LC-EM a fim de identificar eventual presença dos monômeros Bis-GMA e TEGDMA. As amostras de fluido crevicular foram analisadas utilizando-se método ELISA para identificação e quantificação de interleucinas. Para realizar as comparações inter e intragrupo dos parâmetros clínicos foi utilizado o teste de McNemar para as variáveis categóricas e o teste de Wilcoxon para as variáveis numéricas. Para comparar a classificação do critério FDI entre os tempos foi utilizado o teste de Stuart-Maxwell. Para a análise da saliva, os dados de quantidade de monômeros liberados ao longo do tempo foram submetidos ao teste t de Student e a relação com quantidade total liberada foram correlacionados com o número de restaurações e com o volume total coletado de cada restauração por meio da Correlação de Pearson. O desempenho clínico das restaurações de LCNCs de um sistema restaurador resinoso bulk- fill por meio dos critérios FDI foi considerado satisfatório ao longo de 6 meses. Os parâmetros clínicos periodontais Sangramento a Sondagem, Ìndice Gengival e Profundidade de Sondagem foram mais pronunciados em torno dos dentes restaurados. O material restaurador resinoso bulk-fill não causou alteração estatisticamente significante no volume de FCG e as citocinas ao redor de dentes restaurados na amostra avaliada. Não detectou-se Bis-GMA nas amostras de saliva coletadas antes, 01 e 06 meses após. A liberação de TEGDMA média antes da restauração foi estatisticamente menor do que após 10 minutos. Os resultados do presente estudo sugerem que a restauração do LCNC pode afetar os parâmetros clínicos periodontais, porém não foi capaz de afetar a liberação de citocinas e o volume de FCG. A liberação de Bis-GMA não foi considerada significante ao longo de 6 meses, entretanto a liberação de TEGDMA foi expressiva apenas 10 minutos após a execução da restauração.

Most composite resins present methacrylates as the main monomers of their composition. In composite resins, the release of methacrylate monomers, associated with the polymerization products, has been considered as the source of a series of biological reactions such as toxicity or pulp reactions. The objectives of this study were to evaluate the clinical performance of NCCL restorations with composite resin, to determine also the presence of IL-1ß and IL-6 cytokines in the gingival crevicular fluid (GCF) and the release of resinous components to saliva. The FL-Bond II restorative system (adhesive system) / Beautifil Bulk (restorative composite resin) was used. A longitudinal clinical study was performed in vivo, where patients with a non-carious cervical lesion with a restorative need were selected. Anterior and posterior teeth with NCCL and sensitivity were designated as experimental group and the corresponding tooth as control group. Prior to the treatment, were performed periodontal evaluation, collection of saliva and gingival crevicular fluid. The lesions were restored and, after 10 minutes, 7 days, 1 month and 6 months, there was a clinical evaluation of the restorations according to the FDI criteria and the periodontal response were made. Additionally, in all of these evaluation periods there was collection of saliva and crevicular fluid were colleted. Saliva samples were analyzed by LC-MS in order to identify the possible presence of monomers. Crevicular fluid samples were analyzed using the ELISA method for identification and quantification of interleukins. To perform intra- and inter group comparisons of clinical parameters, the McNemar test for categorical variables and the Wilcoxon test for numerical variables were used. To compare the classification of the FDI criterion between the times, the Stuart-Maxwell test was used. For the analysis of saliva, the data of quantity of monomers released over time were submitted to Student's t-test and the relation with total amount released were correlated with the number of restorations and with the total volume collected from each restoration by means of Pearson's Correlation. The clinical performance of NCCL restorations of a bulk-fill resin restorative system by FDI criteria was considered satisfactory over 6 months. Considering the periodontal response of the surrounding tissue to the NCCL restorations, it was observed that periodontal clinical parameters Bleeding on Probing, Gingival Index and Prohibing on Depth were more pronounced around the restored teeth. The bulk-fill resin restorative material did not cause statistically significant changes in the volume of GCF and in the IL-1ß and IL-6 cytokines around restored teeth in the evaluated sample. No Bis-GMA was detected in the saliva samples collected before, 01 and 06 months after. For the Bis-GMA, there was no statistical difference between the analyzed periods. The mean TEGDMA release before the restoration was statistically lower than after 10 minutes. The results of the present study suggest that NCCL restoration may affect periodontal clinical parameters, but it was not able to affect the release of cytokines and the volume of GCF. The release of Bis-GMA was not considered significant over 6 months. However, the release of TEGDMA was significant only 10 minutes after the restoration was performed.

O papel das citocinas na peri-implantite ­ revisão narrativa da literatura / The role of cytokines on peri-implantitis ­ a narrative literature review

O objetivo desta revisão da literatura narrativa foi tentar fornecer um melhor entendimento sobre o papel das citocinas encontradas no fluido peri-crevicular (FCPI) e associadas à peri-implantite (PI). As citocinas são mediadores inespecíficos da resposta inflamatória, com atividades quimiotáticas, efeito direto antiviral, ou ação citotóxica, detectadas por exames como o ELISA e o multiplex. Na comparação entre sítios peri-implantares sadios e doentes, citocinas como a IL4, IL-6, IL-8, IL-10, IL-12, IL-17, IL-1ß, TNF-α e a tríade RANKL/RANK/OPG podem ser vistas, entretanto, algumas vezes não associadas significativamente (com correlações positivas ou negativas) aos valores de sangramento a sondagem, nível de inserção clínica ou profundidade de bolsa. A evidência científica atual com número reduzido de estudos prospectivos não sustenta se as citocinas do FCPI podem ser utilizadas como um método diagnóstico eficaz no monitoramento longitudinal dos tecidos peri-implantares. Ainda, não existem testes disponíveis na clínica diária, tampouco uma citocina específica é usada como biomarcador no diagnóstico precoce da PI.

This narrative literature review attempts to provide a better understanding on the role of cytokines at the peri-implant crevicular fl uid (PICF) and associated to peri-implantitis (PI). Cytokines are unspecific mediators of the inflammatory response, with chemotaxis, antiviral, and cytotoxic actions, detected by ELISA or multiplex methods. Regarding healthy and affected peri-implant sites, factors such as IL4, IL-6, IL-8, IL-10, IL-12, IL-17, IL-1ß, TNF-α, and the RANKL/RANK/OPG triad can be seen, but sometimes not statistically associated (positive or negative relationships) to bleeding on probing, clinical attachment level, or pocket depth values. The contemporary scientific evidence with its reduced number of prospective studies does not support that the cytokines found at the PICF can be used as an efficient diagnostic method for long-term peri-implant tissue monitoring. In addition, no tests are available for routine clinical use and no single cytokine is used as a biomarker for early PI diagnosis.

Análise dos níveis das interleucinas tipo 10 e 1β após aplicação da pasta de iodofórmio na região peri-implantar: estudo piloto / Interleukins 10 and 1β levels in peri-implant region after using iodoform paste in periimplant region: a pilot study

O dano tecidual que leva a perda do implante dentário está intimamente relacionado à resposta inflamatória local. A utilização de medicamentos tópicos tem sido estudada como forma de controlar essa resposta inflamatória, evitando assim perda óssea após o período de osseointegração. Objetivo: avaliar os níveis de IL-10 e IL-1β no fluido crevicular peri-implantar após utilização de uma pasta à base de iodofórmio em humanos. Material e métodos: vinte regiões em 3 pacientes foram divididas em dois grupos: grupo A (reabertura dos implantes e instalação do cicatrizador) e grupo B (reabertura do implante e instalação do cicatrizador juntamente com uma pasta de iodofórmio). Quinze dias após a exposição dos implantes, amostras do fluido crevicular peri-implantar (FCPI) foram obtidas, utilizando filtro de papel absorvente inserido ao sulco peri-implantar, durante 30 s, após a remoção do cicatrizador. Os níveis de IL-10 e IL-1β nas amostras foram determinados por ELISA utilizando o kit DuoSet ELISA Development System DY217B. Após o Teste de Shapiro-Wilk, o teste de Tukey foi utilizado para determinar o valor de p na avaliação das diferenças entre os grupos, com nível de significância de 0,05. Resultados: não houve diferença significativa entre as concentrações de IL-10 nos dois grupos (p=0.34). No entanto, diferença significativa foi evidenciada entre os grupos A e B em relação aos níveis de IL-1β (p=0.03). O grupo B mostrou significativa menor concentração de IL-1β comparado ao grupo A. Conclusão: a pasta de iodofórmio é capaz de diminuir a resposta pró-inflamatória orquestrada pela IL-1β em um curto período de tempo

The tissue damage around dental implant is strictly related to inflammatory response. The use of local drugs has been studied as a tempt of controlling this response in order to avoid the bone loss after osseointegration period. Aim: to evaluate the interleukins 10 and 1β levels in peri-implant crevicular fluid after using iodoform paste in humans. Material and methods: twenty regions, in 03 patients, were divided in 2 groups; group A (implant exposure and healing insertion) and group B (implant exposure and healing/ iodoform paste insertion). Fifteen days after exposure, samples from peri-implant crevicular fluid were collected. ELISA technique determined the interleukins 10 and 1β levels by using DuoSet ELISA Development System DY217B kit. Tukey test analysed differences between groups, considering 0.05 significant level. Results: no difference was observed between groups considering interleukin 10 levels (p=0.34). however, significant differente was observed considering the interleukin 1β levels (p=0.03). Group B showed significant smaller IL-1β level than group A. Conclusion: iodoform paste is able to decrease the pro-inflammatory response conduct by interleukin 1β.