Correlation of fasting blood, salivary glucose and malondialdehyde in subjects with & without type 2 diabetes

Oxidative stress is identified as the common pathogenic factor that leads to insulin resistance in diabetics. Malondialdehyde is a product of lipid peroxidation. Aim: The aim of this study was to determine the variation in the Salivary malondialdehyde (MDA) among subjects with and without T2DM in comparison to the fasting blood and Salivary glucose. Methods: This study involved 29 healthy participants as Controls (group I) and 29 participants with Type 2 Diabetes Mellitus as Cases (group II). Salivary Glucose was analysed by glucose oxidase end-point assay. Thiobarbituric acid (TBA) assay method was considered for estimation of MDA in fasting saliva. Data was Statistically analysed using SPSS20. Parametric test was performed to analyse the data. Results: The correlation calculated between FBG with FSG level was found to be highly significant. A positive correlation between MDA levels with FBG was found. The relationship between FBG and FSG (r = 0.7815, p < 0.05), FBG and MDA (r =0.3678, p < 0.05) and FSG and MDA (r = 0.2869, p < 0.05) were found to be positively significant. Conclusion: Saliva as a unique body fluid can serve as a medium for biochemical analysis only in standard settings and with multiple measures to be used as a diagnostic tool in par with the gold standard serum. Salivary MDA levels can be considered as one of the oxidative stress markers in Type 2 Diabetic condition

Sensitivity and specificity of salivary pipecolic acid in head and neck squamous cell carcinoma

Aim: The aim of the present preliminary case-control study was to test the sensitivity and specificity of salivary pipecolic acid in predicting head and neck squamous cell carcinoma (HNSCC). Methods: High-performance liquid chromatography was used for the analysis of non-stimulated saliva samples from 40 individuals: 20 in the case group (recently diagnosed with untreated HNSCC) and 20 in the control group (individuals without cancer). Both groups included patients taking daily oral hypoglycemic drugs (comorbidity). The case and control groups were matched at a proportion of 1:1 for sex and comorbidity. Results: Mean salivary levels of pipecolic acid were 169.38 ng/ mL in the case group and 114.66 ng/mL in the control group (p<0.001). Individuals who took oral hypoglycemic drugs had higher levels of pipecolic acid in both the case and control groups (p<0.001). The receiver operating characteristic curve analysis revealed 90% sensitivity and 65% specificity for head and neck cancer, with an area under the curve of 0.838 between the case and control groups. Conclusions: Pipecolic acid had high sensitivity for the diagnosis of HNSCC but low specificity in the sample analyzed. Our findings suggest that salivary pipecolic acid levels are associated with glucose homeostasis. Studies with larger samples are required to evaluate the specificity of this metabolite

Unlocking the secrets of saliva: the promising potential of salivary biomarkers for evaluating crack use / Desvendando os segredos da saliva: o potencial promissor dos biomarcadores salivares para avaliar o uso de crack

The forthcoming letter will encompass the following highlights: Crack cocaine use involves smoking a highly addictive form of cocaine, which is a significant concern in Brazil, particularly in urban areas. This addiction is linked to various health problems, including cardiovascular issues, sexually transmitted infections (STIs) like AIDS and syphilis, tuberculosis, and a notable increase in mortality, largely due to violent causes. Furthermore, crack cocaine users are particularly vulnerable to dental caries, gingival inflammation, oral mucosa lesions, and xerostomia (AU)

A próxima carta incluirá os seguintes destaques: O uso de crack envolve fumar uma forma altamente viciante da cocaína, o que é uma preocupação significativa no Brasil, especialmente em áreas urbanas. Esta dependência está ligada a vários problemas de saúde, incluindo problemas cardiovasculares, infecções sexualmente transmissíveis (IST), como a AIDS e a sífilis, a tuberculose e um aumento notável da mortalidade, devido, em grande parte, a causas violentas. Além disso, os usuários de crack são particularmente vulneráveis a cáries dentárias, inflamação gengival, lesões na mucosa oral e xerostomia (AU)

Comparative Assessment of E-cadherin's Expression between the Metastatic and Non-metastatic Oral Squamous Cell Carcinoma: An Immunohistochemical Study

ABSTRACT Objective: To identify the clinicopathological correlation of E-cadherin expression in metastatic and non-metastatic oral squamous cell carcinoma (OSCC). Material and Methods: A total of 90 paraffin-embedded tissue sections of OSCC were retrieved from the registry. The total selected samples were 45 cases each from the primary lesions of metastatic and non-metastatic OSCC. One section was subjected to routine Hematoxylin and eosin stain and another to immunohistochemical analysis for E-cadherin expression. Results: A non-significant (p˃0.05) increased expression is seen in the non-metastatic group compared to the metastatic group, with predominantly membrane as the staining site in either group. However, the expression of E-cadherin did not reveal any statistically significant association with independent variables such as age, gender, and adverse habits of the patients (p>0.05). On the other hand, with respect to the histological differentiation of OSCC, a significant association (p<0.001) was observed with the well-differentiated type of metastatic OSCC. Conclusion: E-cadherin was useful to some extent in predicting regional metastasis. However, further studies using a panel of biomarkers with increased sample size may help us understand the process involved in metastasis.

Biomarcadores da homeostase redox em saliva e alterações nucleares no epitélio da mucosa jugal de indivíduos com diabetes mellitus tipo 2 e periodontite / Oxidative stress biomarkers in saliva and nucear changes in epithelial cells of indivudals with type e Diabetes Mellitus and periodontitis

O presente estudo é composto por dois capítulos, sendo o primeiro um artigo de revisão sistemática que abordou as evidências científicas para a diferença de biomarcadores do estresse oxidativo em indivíduos com diabetes mellitus tipo 2 com e sem periodontite. Foram incluídos 9 estudos na análise final, pesquisados através das seguintes bases de dados: PubMed, Scopus, Embase, Web of Science, Cochrane Library, Biblioteca Virtual da Saúde e por outras fontes. Os estudos relataram elevadas concentrações de agentes oxidantes e baixos níveis de antioxidantes em indivíduos com diabetes mellitus tipo 2 e periodontite quando comparados aos indivíduos sem periodontite. Considerando os poucos estudos encontrados, as falhas metodológicas, poucos marcadores estudados e ausência de homogeneidade na avaliação dos marcadores do balanço redox, bem como, a baixíssima certeza da evidência entre os estudos incluídos nesta revisão sistemática, não foi possível determinar se há ou não diferenças nos níveis de estresse oxidativo em indivíduos com diabetes mellitus tipo 2 associado ou não à periodontite e, portanto, estudos observacionais prospectivos e de intervenção são recomendados. O segundo capítulo é um artigo de pesquisa que retrata a periodontite e o diabetes mellitus tipo 2 como doenças com características de inflamação crônica e com estresse oxidativo permanentemente elevado, o que afeta o padrão de funcionamento do sistema imunológico e resulta em danos a importantes macromoléculas biológicas. Trata-se de um estudo observacional, que objetivou avaliar biomarcadores da homeostase redox em saliva e a presença de alterações nucleares em pacientes com periodontite com ou sem diabetes tipo 2 e em indivíduos periodontalmente e sistemicamente saudáveis. Um total de 60 participantes foram divididos igualmente em três grupos: diabetes tipo 2 com periodontite (DPE); sem diabetes com periodontite (PE); saudáveis sem doença periodontal (HC). Após as medições clínicas periodontais, as células epiteliais da mucosa jugal e a amostra de saliva foram coletadas. O dano ao DNA foi determinado pela contagem de micronúcleos e anormalidades nucleares em células epiteliais. Os níveis de estresse oxidativo foram determinados por glutationa reduzida (GSH), ácido úrico (UA), capacidade antioxidante total (TAC), substâncias reativas ao ácido tiobarbitúrico (TBARs) e proteínas totais. Os dados numéricos foram testados pelos testes de Mann-Whitney e Kruskal-Wallis, as variáveis numéricas pelo teste do qui-quadrado e as correlações pelo coeficiente de Spearman, regressões linear e logística foram realizadas, adotando o nível de significância de 5%. As frequências de micronúcleos, cariorrexia, cromatina condensada e células picnóticas, e dos biomarcadores GSH e UA foram significativamente maiores no grupo DPE seguido dos grupos PE e HC (p<0,05). Glicemia em jejum, hemoglobina glicada, frequência de micronúcleos (MN), anormalidades nucleares (NA - cariorrexia, cromatina condensada e células picnóticas), GSH e UA apresentaram de leve a moderada correlação positiva com os parâmetros de progressão da periodontite (p<0,05). A análise de regressão linear mostrou que GSH categorizada teve correlação com sangramento gengival (p = 0,002) e TBARs (p = 0,020) e UA com sangramento à sondagem (p = 0,001) e TAC (p = 0,001). A análise de regressão logística mostrou que os níveis categorizados de GSH tiveram correlação com sangramento à sondagem (OR = 1,121 [95% CI, 1,025-1,225]) e supuração (OR = 0,155 [95% CI, 0,029-0,838]). Portanto, as correlações positivas entre os parâmetros periodontais, MN, NA (cromatina condensada, células cariorréticas e picnóticas), e os parâmetros redox na saliva (GSH e UA) refletem piores condições periodontais e dos parâmetros do diabetes mellitus tipo 2. Os biomarcadores na saliva (GSH e UA) apresentaram um importante papel na detecção de alteração no funcionamento do balanço redox e dos danos nucleares em células epiteliais da mucosa jugal. (AU)

This study consists of two chapters, the first is a systematic review article which addressed the scientific evidence for the difference of oxidative stress biomarkers in individuals with type 2 diabetes mellitus with and without periodontitis. Nine studies were included in the final analysis, searched through the following databases: PubMed, Scopus, Embase, Web of Science, Cochrane Library, Virtual Health Library and other sources. The studies reported high concentrations of oxidizing agents and low antioxidants levels in individuals with type 2 diabetes mellitus and periodontitis when compared to with no periodontitis. Considering the few studies found, the methodological flaws, few markers studied and absence homogeneity in the evaluation of redox balance markers, as well as, the very low certainty of the evidence among included studies in this systematic review, it was not possible to determine whether there are or not differences in the oxidative stress levels in individuals with type 2 diabetes mellitus associated or no with periodontitis and further prospective observational and interventional studies are recommended. The second chapter is a research article that describe the periodontitis and type 2 diabetes mellitus as diseases with features of chronic inflammation and with oxidative stress permanently elevated which affects the pattern of functioning of the immune system and results in damage to important biological macromolecules. This is an observational study, which aimed to evaluate redox homeostasis biomarkers in saliva and the presence of nuclear changes in patients with periodontitis with and without type 2 diabetes and periodontally and systemically healthy individuals. A total of 60 participants were allotted into three groups equally: type 2 diabetes with periodontitis (DPE); non-diabetes with periodontitis (PE); healthy without periodontal disease (HC). After periodontal measurements, cheek epithelial cells and saliva samples were collected. DNA damage was determined by counting micronucleus and nuclear abnormalities in epithelial cells. Oxidative stress levels were determined by reduced glutathione (GSH), uric acid (UA), total antioxidant capacity, thiobarbituric acid reactive substances, and total proteins. Numeric data were tested by Mann-Whitney and Kruskal-Whallis tests, qualitative variables by chi-square test and correlations by the spearman coeficiente, and linear and logistic regression were performed, adopting the significance level of 5%. The frequencies of micronucleus (MN), karyorrhectic, condensed chromatin, pyknotic cells, GSH and UA were significantly higher in DPE group followed PE and HC groups (p<0.05). Fasting blood glucose, glycated hemoglobin, MN and nuclear abnormalities (NA) frequencies (karyorrhectic, condensed chromatin and pyknotic cells), GSH and UA showed a positive mild to moderate correlation with periodontitis progression parameters (p<0.05). Linear regression analysis showed that categorized GSH had correlation with gingival bleeding (p = 0.002) and TBARs (p = 0.020) and UA with bleeding on probing (p = 0.001) and TAC (p = 0.001). Logistic regression analysis showed that categorized GSH levels had correlation with bleeding on probing (OR = 1.121 [95% CI, 1.025-1.225]) and supuration (OR = 0.155 [95% CI, 0.029-0.838]). Therefore, positive correlations among periodontal parameters, MN, NA, and salivary oxidative stress biomarkers (GSH and UA) reflects worse periodontal conditions and of the type 2 diabetes mellitus parameters. Salivary biomarkers (GSH and UA) played an important role in the detection the functioning of the redox balance and nuclear damage in cheek epithelial cells. (AU)

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)

A influência dos cuidados periodontais sobre os biomarcadores inflamatórios de pacientes com COVID-19 / The influence of periodontal care on inflamatory biomarkers of patients with COVID-19

A infecção causada pelo novo coronavírus (SARS-CoV-2), denominada pela Organização Mundial de Saúde como COVID-19 é capaz de provocar complicações graves em seres humanos, tais como Síndrome Respiratória Aguda Grave (SRAG), tromboembolismo venoso, alterações cardiovasculares, lesões hepática e renal agudas, entre outras que podem levar à hospitalização e mortalidade do indivíduo. O mecanismo responsável por estas complicações seria uma suposta resposta hiperinflamatória do organismo que leva ao aumento de biomarcadores inflamatórios sanguíneos. Algumas condições de saúde como hipertensão arterial, diabetes, obesidade e doença renal crônica são apontadas como fatores de risco capazes de aumentar a morbidade da doença. Neste contexto, a literatura científica da atualidade sugere a associação entre a má qualidade de saúde bucal dos pacientes e o aparecimento destas doenças. Quadros infecciosos bucais como a doença periodontal crônica também são supostamente responsáveis por um aumento destes biomarcadores inflamatórios. Diante do exposto, o objetivo deste trabalho é avaliar, a partir de uma revisão da literatura disponível, o impacto dos cuidados de saúde bucal sobre os biomarcadores inflamatórios de pacientes portadores de COVID-19 hospitalizados.

The infection caused by the new coronavirus (SARS-CoV-2), called by the World Health Organization as COVID-19, is able to cause serious complications in humans, such as Severe Acute Respiratory Syndrome, venous thromboembolism, cardiovascular alterations, liver and kidney injuries, among others that can lead to hospitalization and mortality of the individual. The mechanism responsible for these complications would be a supposed hyperinflammatory response of the body that leads to an increase in blood inflammatory biomarkers. Some health conditions such as high blood pressure, diabetes, obesity and chronic kidney disease are identified as risk factors capable of increasing the morbidity of the disease. In this context, the current scientific literature suggests an association between the poor quality of oral health of patients and the onset of these diseases. Oral infectious conditions such as chronic periodontal disease are also supposedly responsible for an increase in these inflammatory biomarkers. The aim of this study is to evaluate, based on a review of the available literature, the impact of oral health care on inflammatory biomarkers in hospitalized patients with COVID-19.

A medicina periodontal no contexto da pandemia de COVID-19 e obesidade, e a importância da avaliação hepática em pacientes com periodontite / Periodontal Medicine in the context of the COVID-19 pandemic and obesity, and the importance of liver assessment in patients with periodontitis

A presente Tese teve como objetivo desenvolver um ensaio teórico sobre a importância da patogênese da COVID-19 na pesquisa em Medicina Periodontal, e realizar uma síntese das evidências científicas sobre a relação entre obesidade e periodontite, a importância da PCR enquanto biomarcador de impacto sistêmico da periodontite, e os efeitos da bacteremia e endotoxemia por patógenos periodontais e suas toxinas no fígado. Desenvolvemos uma pesquisa bibliográfica sistematizada e de delineamento misto, cujos objetivos foram explorados em estudos individuais apresentados em seis capítulos. Os resultados sugerem que a COVID- 19 e periodontite compartilham mecanismos de patogênese e fatores de risco que podem influenciar os estudos em Medicina Periodontal. Os efeitos da obesidade na periodontite parecem estar relacionados com o aumento de biomarcadores inflamatórios e complicações associadas às desordens no metabolismo da glicose. Existem evidências da associação entre obesidade e parâmetros clínicos periodontais, resistina e IL-1b no FCG, bem como de melhora da pressão arterial, colesterol total, LDL, triglicerídeos, HbA1c, resistência insulínica, PCR, IL- 1ß, TNF-α e C3 no sangue, quemerina, vaspina, omentina-1, visfatina, e 8-OHdG no FCG após o tratamento da periodontite. Alguns patógenos periodontais também reduziram em quantidade. As evidências atuais confirmam a redução de PCR após o tratamento da periodontite em pacientes com diabetes tipo 2, pré-hipertensão e hipertensão arterial, e insuficiência renal submetidos a hemodiálise e/ou diálise peritoneal. Além do aumento de PCR, o fígado desenvolve doença NAFL, NASH e fibrose avançada por ação direta de patógenos periodontais e LPS bacteriano, a partir da corrente sanguínea e do eixo boca-intestino-fígado. Casos graves de patologia hepática foram associados à bacteremia por patógenos bucais. Portanto, a obesidade e a avaliação hepática devem ser consideradas em novas pesquisas e na prática clínica em Medicina Periodontal. A evidência de associação entre a periodontite e níveis séricos de PCR reforça seu papel como biomarcador de risco sistêmico, e os efeitos da COVID-19 na patogênese das doenças periodontais e sistêmicas devem ser considerados. (AU)

This thesis aimed to develop a theoretical essay on the importance of the pathogenesis of COVID-19 in research in Periodontal Medicine, and to perform a synthesis of the scientific evidence on the relationship between obesity and periodontitis, the importance of CRP as a biomarker of the systemic impact of periodontitis. and the effects of bacteremia and endotoxemia by periodontal pathogens and their toxins on the liver. We developed a systematic literature search with a mixed design, whose objectives were explored in individual studies presented in six chapters. The results suggest that COVID-19 and periodontitis share pathogenesis mechanisms and risk factors that may influence studies in Periodontal Medicine. The effects of obesity on periodontitis seem to be related to the increase in inflammatory biomarkers and complications associated with disturbances in glucose metabolism. There is evidence of an association between obesity and periodontal clinical parameters, resistin and IL- 1b in GCF, as well as improvement in blood pressure, total cholesterol, LDL, triglycerides, HbA1c, insulin resistance, CRP, IL-1ß, TNF -α and Blood C3, chemerin, vaspin, omentin-1, visfatin and 8-OHdG in FCG after periodontitis treatment. Some periodontal pathogens were also reduced in quantity. Current evidence confirms the reduction of CRP after treatment of periodontitis in patients with type 2 diabetes, pre-hypertension and arterial hypertension and renal failure on hemodialysis and/or peritoneal dialysis. In addition to increased CRP, the liver develops NAFL disease, NASH and advanced fibrosis by the direct action of periodontal pathogens and bacterial LPS from the bloodstream and the mouth-gut-liver axis. Severe cases of liver pathology have been associated with bacteremia by oral pathogens. Therefore, obesity and liver assessment should be considered in new research and clinical practices in Periodontics. Evidence of an association between periodontitis and serum CRP levels reinforces its role as a biomarker of systemic risk, and the effects of COVID-19 on the pathogenesis of periodontal and systemic diseases should be considered. (AU)

Does oral lichen planus aggravate the state of periodontal disease? A systematic review and meta-analysis

OBJETIVO: O objetivo desta revisão sistemática e metanálise (SRM) foi avaliar as evidências entre a associação de líquen plano oral (OLP) e doença periodontal, avaliando os parâmetros clínicos periodontais e os níveis de biomarcadores. MATERIAIS E MÉTODOS: Esta revisão sistemática e meta-análise seguiu PRISMA e foi registrada no PROSPERO (CRD42020181513). Foram realizadas buscas em bases de dados de artigos publicados até junho de 2021. A metanálise foi realizada com as variáveis: índice de placa (PI), índice gengival (GI), profundidade de sondagem (PD) e perda de inserção clínica (CAL). A diferença média foi aplicada com intervalo de confiança de 95%. RESULTADOS: 6 artigos foram incluídos. A análise qualitativa mostrou que os níveis de biomarcadores (metaloproteinases de matriz, interleucinas e perfil microbiológico periodontal) estão aumentados em indivíduos com doença periodontal e líquen plano oral. Na metanálise, esses indivíduos também apresentaram aumentos em todos os parâmetros clínicos periodontais avaliados: GI­ gengivite 0,22 [0,14, 0,31] p< 0,0001 e periodontite 0,12 [0,06, 0,19] p=0,0003; PI­ gengivite 0,22 [0,12, 0,31] p< 0,0001 e periodontite 0,15 [0,08, 0,23] p< 0,0001; PD­ gengivite 0,27 [0,06; 0,48] p=0,0107 e periodontite 0,11 [0,01; 0,21] p=0,0299; e CA ­ periodontite 0,06 [0,01, 0,12] p=0,0176. CONCLUSÕES: Evidências sugerem uma relação significativa entre a gravidade da doença periodontal e a presença de líquen plano oral. RELEVÂNCIA CLÍNICA: Este SRM fornece informações sobre a interação entre OLP e a doença periodontal e orienta os médicos a tomar decisões baseadas em evidências e sugere recomendações para estudos adicionais de alta qualidade(AU)

BACKGROUND: The objective of this systematic review and meta-analysis (SRM) was to assess the evidence between the association of oral lichen planus (OLP) and periodontal disease, evaluating the periodontal clinical parameters and biomarkers levels. METHODS: This systematic review and meta-analysis followed PRISMA and was registered in PROSPERO (CRD42020181513). Searches were accomplished in databases for articles published until June 2021. The meta-analysis was performed with the variables: plaque index (PI), gingival index (GI), probing depth (PD), and clinical attachment loss (CAL). The mean difference was applied with a 95% confidence interval. RESULTS: 6 articles were included. Qualitative analysis showed the levels of biomarkers (matrix metalloproteinases, interleukins, and periodontal microbiological profile) are increased in subjects with periodontal disease and oral lichen planus. In the meta-analysis, these subjects also presented increases in all periodontal clinical parameters evaluated: GI­ gingivitis 0.22 [0.14, 0.31] p < 0.0001 and periodontitis 0.12 [0.06, 0.19] p =0.0003; PI­ gingivitis 0.22 [0.12, 0.31] p < 0.0001 and periodontitis 0.15 [0.08, 0.23] p < 0.0001; PD­ gingivitis 0.27 [0.06; 0.48] p=0.0107 and periodontitis 0.11 [0.01; 0.21] p=0.0299; and CA ­ periodontitis 0.06 [0.01, 0.12] p=0.0176. CONCLUSIONS: Evidence suggests a significant relationship between the severity of periodontal disease and the presence of oral lichen planus. CLINICAL RELEVANCE: This SRM provides information on the interaction between OLP and periodontal disease and guides clinicians to make evidence-based decisions and suggests recommendations for further high-quality studies(AU)

Salivary nitrite and systemic biomarkers in obese individuals with periodontitis submitted to FMD

Abstract The objective of this 9-month clinical study is to assess the impact of one-stage full-mouth disinfection (FMD) on salivary nitrite levels and systemic biomarkers and its correlation with total subgingival bacterial load in obese and non-obese patients with periodontitis. In total, 94 patients (55 obese and 39 non-obese) were initially evaluated, seven were lost during follow-up, resulting in 87 individuals at the end of the study. Outcomes were assessed at baseline, 3, 6, and 9 months post periodontal treatment by FMD. Salivary nitrite levels were determined using Griess reagent. Blood samples were collected to determine C-Reactive Protein (CRP), alkaline phosphatase and fasting blood glucose. Real-time PCR was used to determine the total subgingival bacterial load. FMD protocol resulted in increased salivary nitrite levels at 6- and 9-months post-treatment in the non-obese group (p<0.05). In obese individuals, FMD treatment led to an increase in salivary nitrite levels at 6 months (p<0.05); however, at 9 months, the nitrite levels returned to baseline levels. For both groups, the highest nitrite values were observed at 6 months. In addition, in both groups, FMD was associated with a decrease in biomarkers related to systemic inflammation and cardiovascular diseases, such as CRP (p<0.05) and alkaline phosphatase (p<0.05), and had no impact on the fasting blood glucose. This study demonstrates that obese patients with periodontitis present similar salivary nitrite levels when compared with non-obese individuals. FMD protocol resulted in increases in salivary nitrite levels and was associated with a positive impact on systemic biomarkers, regardless of obesity status.

Resumo O objetivo deste estudo clínico, é avaliar o impacto da desinfecção bucal completa (DBC) nos níveis de nitrito salivar e biomarcadores sistêmicos e sua correlação com a carga bacteriana subgengival total em pacientes obesos e não obesos com periodontite. No total, 94 pacientes (55 obesos e 39 não obesos) foram avaliados inicialmente, sete foram perdidos durante o estudo, resultando em 87 indivíduos ao final. Os resultados foram avaliados no início do estudo, 3, 6 e 9 meses após o tratamento periodontal por DBC. Os níveis de nitrito salivar foram determinados usando o reagente de Griess. Amostras de sangue foram coletadas para determinação da Proteína C Reativa (PCR), fosfatase alcalina e glicemia de jejum. A PCR em tempo real foi usada para determinar a carga bacteriana subgengival total. O protocolo de DBC resultou em níveis aumentados de nitrito salivar em 6 e 9 meses após o tratamento no grupo de não obesos (p <0,05). Em indivíduos obesos, o tratamento da DBC levou a um aumento nos níveis de nitrito salivar em 6 meses (p <0,05); no entanto, aos 9 meses, os níveis de nitrito voltaram aos níveis basais. Para ambos os grupos, os maiores valores de nitrito foram observados aos 6 meses. Além disso, em ambos os grupos, a DBC foi associada à diminuição dos biomarcadores relacionados à inflamação sistêmica e doenças cardiovasculares, como PCR (p <0,05) e fosfatase alcalina (p <0,05), e não teve impacto na glicemia de jejum. Este estudo demonstra que pacientes obesos com periodontite apresentam níveis de nitrito salivar semelhantes quando comparados a indivíduos não obesos. O protocolo de DBC resultou em aumentos nos níveis de nitrito salivar e foi associado a um impacto positivo nos biomarcadores sistêmicos, independentemente do status de obesidade.

Efeitos da terapia de reposição com testosterona e do chá mate (Ilex paraguariensis) nos parâmetros bioquímicos, funcionais e redox da saliva de ratos orquiectomizados / Effects of testosterone replacement therapy and mate tea (Ilex paraguariensis) on biochemical, functional and redox parameters of saliva in orchiectomized rats

Apesar dos efeitos já conhecidos da testosterona (T) e do chá mate (CM) [Ilex paraguariensis] no estado redox de diversos tecidos biológicos, pouco se sabe a respeito de seus efeitos na saliva. O objetivo foi avaliar os efeitos da terapia de reposição com testosterona (TRT) e do CM nos parâmetros bioquímicos, funcionais e redox da saliva de ratos orquiectomizados. Sessenta ratos Wistar (3 meses de idade) foram castrados bilateralmente ou sofreram cirurgia fictícia (SHAM) e distribuídos aleatoriamente em cinco grupos: SHAM, OQX, UT (castrados que receberam injeção única de undecanoato de testosterona 100 mg/kg, CM (castrados que receberam CM 20 mg/kg, via gavagem intragástrica, diariamente) e UT+CM. Todos os tratamentos começaram 4 semanas após a castração e duraram 4 semanas. Ao final do tratamento, a secreção salivar foi estimulada por pilocarpina para determinação da taxa de fluxo salivar (TFS), pH, capacidade tamponante (CTS), além da análise da composição bioquímica pela mensuração da proteína total (PT), amilase (AMI), eletrólitos e biomarcadores de estresse oxidativo. TFS, CTS, cálcio, fósforo, cloreto, capacidade antioxidante total (CAT), substâncias reativas ao ácido tiobarbitúrico (TBARS), proteína carbonilada (PC) aumentaram com a OQX, enquanto o conteúdo de PT e atividade da AMI na saliva decaíram no grupo OQX. Já o pH, sódio e potássio salivar não foram alterados. A administração de CM aumentou a TFS, cálcio, fósforo, cloreto, CAT e PC. Por outro lado, o grupo CM sofreu redução da PT, enquanto o pH, CTS, AMI, sódio, potássio e TBARS não sofreram nenhuma alteração em relação ao grupo SHAM. Os grupos UT e UT+CM não sofreram qualquer tipo de alteração em relação ao SHAM. TRT com UT restaurou os parâmetros bioquímicos, funcionais e redox da saliva em ratos castrados. CM não teve um efeito semelhante à T na função da glândula salivar, no entanto, pode ser considerada uma ferramenta para aliviar o estresse oxidativo salivar induzido pela OQX(AU)

Despite the known effects of testosterone (T) and mate tea (MT) on the redox state of different biological tissues, little is known about their effects on saliva. The objective was to evaluate the effects of testosterone replacement therapy (TRT) and MT [Ilex paraguariensis] on biochemical, functional, and redox parameters of saliva in orchiectomized rats (ORX). Sixty young adult male Wistar rats (3 months old) were either castrated bilaterally or underwent fictitious surgery (SHAM) and were distributed into 5 groups: SHAM, ORX, TU (castrated rats that received a single intramuscular injection of testosterone undecanoate 100 mg/kg body weight (BW), MT (castrated rats that received MT 20 mg/kg BW, via intragastric gavage, daily) and TU+MT. All treatments started 4 weeks after castration and lasted 4 weeks. At the end of treatment, pilocarpine-induced salivary secretion was collected for analyzing of salivary flow rate (SFR) and biochemistry composition by determination of total protein (TP), amylase (AMY), electrolyte and biomarkers of oxidative stress. TFS, salivary buffering capacity (CTS), calcium, phosphorus, chloride, total antioxidant capacity (CAT), thiobarbituric acid reactive substances (TBARS), protein carbonyl (PC) increased with ORX. While the PT content and AMI activity in saliva decreased in the OQX group. On the other hand, salivary pH, sodium and potassium were not altered. MT administration increased TFS, calcium, phosphorus, chloride, CAT and PC. On the other hand, the MT group suffered a reduction in PT, while the pH, CTS, AMI, sodium, potassium and TBARS did not change in relation to the SHAM group. The TU and TU+MT groups did not suffer any changes in relation to SHAM. TRT with long-acting TU restored the biochemical, functional, and redox parameters of saliva in orchiectomized rats. MT did not have a testosterone-like effect on salivary gland function, however, it could be considered a tool to alleviate the salivary oxidative stress induced by orchiectomy(AU)

Prevalence of Temporomandibular Disorders and its Correlation with Stress and Salivary Cortisol Levels among Students

ABSTRACT Objective: To evaluate the prevalence of temporomandibular disorders (TMD) in students and to evaluate if any relationship existed between the stress levels, salivary cortisol levels, and TMD. Material and Methods: A total of 348 students, 187 female, and 161 male students, participated in this cross-sectional study. Students were evaluated based on the Research Diagnostic Criteria for TMD. The stress levels were evaluated using the Perceived Stress Scale. The students were divided into the control and TMD groups. Salivary cortisol levels in the salivary samples were analyzed. Results: The prevalence rate of TMDs was 30.7% in the study population. Of the female students, 61% had TMD compared with 46% of male students. Muscle disorders were the most predominant disorder in 14.2% of the students with TMD. The TMD group showed significantly higher salivary cortisol and stress levels than the control group. The TMD group also showed a moderate positive correlation between cortisol and stress levels (p=0.01). Conclusion: The study showed a strong association between salivary cortisol levels, stress, and temporomandibular disorders. Salivary cortisol could be used as a prognostic biomarker for stress while assessing the severity of TMJ problems in stressed individuals.

Biomarcadores salivares do estresse oxidativo em crianças com cárie dentária: revisão sistemática e meta-análises / Salivary biomarkers of oxidative stress in children with dental caries: systematic review and meta-analysis

Objetivo. Avaliar a relação entre biomarcadores salivares de estresse oxidativo e cárie dentária em crianças. Métodos. Estudos realizados em crianças de até 12 anos comparando biomarcadores salivares de estresse oxidativo como malondialdeído (MDA), superóxido dismutase (SOD), ácido úrico, capacidade antioxidante total (TAC) e proteína total, considerando crianças com lesões de cárie dentária e sem cárie foram selecionados. Além disso, parâmetros salivares como fluxo salivar, pH, capacidade tampão e níveis de cálcio foram avaliados. Uma revisão sistemática da literatura foi realizada em 8 bases de dados. A diferença média padronizada (SMD) foi medida usando variância inversa como método estatístico e efeitos aleatórios como modelo de análise, correspondendo a um intervalo de confiança (IC) de 95%. Resultados. Os níveis de TAC foram maiores em crianças afetadas por cárie dentária em comparação com as sem cárie (grupo controle), independentemente da idade (SMD 2,66; IC 1,33; 3,98) ou sexo (SMD 0,98; IC 0,56; 1,39). Quando ajustados para proteína normalizada, os níveis de MDA foram menores no grupo de cárie dentária do que no grupo controle (SMD -16,5; IC - 29,02; -4,00), e os níveis de SOD foram maiores no grupo de cárie dentária (SMD 5,09; IC 0,01; 10,18). A concentração de proteína total na saliva de crianças com cárie dentária foi maior do que no grupo controle, independentemente da idade (SMD 0,98; IC 0,27; 1,69) ou sexo (SMD 0,77; IC 0,45; 1,10). Os parâmetros salivares avaliados apresentaram níveis mais baixos em crianças com cárie dentária (p< 0,05). Conclusões. Os níveis de biomarcadores de estresse oxidativo e parâmetros salivares estão alterados na saliva de crianças com cárie dentária(AU)

Objective. To assess the relationship between salivary biomarkers of oxidative stress and dental caries in children. Methods. Studies conducted in children up to 12 years old comparing salivary biomarkers of oxidative stress such as malondialdehyde (MDA), superoxide dismutase (SOD), uric acid, total antioxidant capacity (TAC), and total protein, considering children with dental caries lesions and caries-free ones were selected. In addition, salivary parameters such as salivary flow, pH, buffering capacity, and calcium levels were evaluated. A systematic literature review was carried out in 8 databases. The standardized mean difference (SMD) was measured using inverse variance as a statistical method and random effects as an analysis model, corresponding to a 95% confidence interval (CI). Results. The TAC levels were higher in children affected by dental caries compared to caries-free ones (control group), regardless of age (SMD 2.66; CI 1.33; 3.98), or gender (SMD 0.98; CI 0.56; 1.39). When adjusted for normalized protein, MDA levels were lower in the dental caries group than in the control group (SMD -16.51; CI -29.02; -4.00), and SOD levels were higher in the dental caries group (SMD 5.09; CI 0.01; 10.18). The total protein concentration in saliva of children with dental caries was higher than in the control group, regardless of age (SMD 0.98; CI 0.27; 1.69), or gender (SMD 0.77; CI 0.45; 1.10). The salivary parameters assessed had lower levels in children affected by dental caries (p<0.05). Conclusions. The levels of oxidative stress biomarkers and salivary parameters are altered in saliva of children with dental caries(AU)

Efeito do tratamento periodontal não cirúrgico em indivíduos com artrite reumatóide e periodontite: aspectos epidemiológicos, clínicos, microbiológicos e biomarcadores / Effect of non-surgical periodontal treatment in individuals with rheumatoid arthritis and periodontitis: epidemiological, clinical, microbiological and biomarkers aspects

Objetivos: Evidências atuais reconhece que a periodontite (PE) e a artrite reumatóide (AR) compartilham comuns fatores de risco e alguns caminhos fisiopatológicos semelhantes, como inflamação crônica induzida por citocinas pró-inflamatórias e destruição de tecidos conjuntivos e ósseos. Assim, esta tese apresenta quatro estudos da possível associação entre PE e AR com os seguintes objetivos: avaliar a condição periodontal, gravidade e extensão da periodontite e aspectos clínicos e epidemiológicos da sua associação com a AR. Investigar a influência do tratamento periodontal não cirúrgico (TPNS) sobre os parâmetros clínicos periodontais, níveis bacterianos de A. actinomycetemcomitans, P. gingivalis, T. forsythia, T dentícola e a atividade da AR (DAS28). Adicionalmente quantificar níveis sanguíneos e salivares dos biomarcadores RANKL, OPG, RANKL / OPG, Survivina, e anticorpos antipeptídeos citrulinados cíclicos (ACPAs) e anti-carbamiladas (Anti-CarP). Métodos: A amostra do estudo foi composta por um total de 471 indivíduos divididos aleatoriamente em grupos, de acordo com o objetivo de cada estudo. O ensaio clínico realizou as seguintes avaliações no início do estudo (T1) e 45 dias (T2) após TPNC: exames periodontais de boca completa, análise microbiológica por meio de qPCR em tempo real, avaliações do Disease Activity Score (DAS-28). Em adição, a quantificação de biomarcadores e anticorpos Anti-Carp e ACPAs realizada por meio de ELISA no soro/saliva. Resultados: O presente estudo reportou uma alta prevalência de PE em indivíduos com AR e uma importante associação entre ocorrência, gravidade e extensão da PE associadas à AR e ao tabagismo. O tratamento periodontal não cirúrgico foi eficaz em melhorar a condição cliníca periodontal, reduziu a presença dos patógenos periodontais avaliados e melhorou o quadro clínico da AR (redução dos escores de DAS-28). Adicionalmente, reduziu os níveis de survivina, RANKL e concentração de ACPAs e Anti-CarP. Conclusão: Nossos achados corroboram a robustez das evidências científicas da associação entre periodontite e AR. Assim, o controle da infecção periodontal em pacientes com AR e PE pode ser uma importante ferramenta terapêutica no controle da AR.

Objectives: Current evidence recognizes that periodontitis (PE) and rheumatoid arthritis (RA) share common risk factors and some similar pathophysiological pathways, such as chronic inflammation induced by pro-inflammatory cytokines and destruction of connective and bone tissues. Thus, this thesis presents four studies of the possible association between PE and RA with the following objectives: to assess the periodontal condition, severity and extent of periodontitis and the clinical and epidemiological aspects of its association with RA. To investigate the influence of non-surgical periodontal treatment (TPNS) on the periodontal clinical parameters, bacterial levels of A. actinomycetemcomitans, P. gingivalis, T. forsythia, T dentic and the activity of RA (DAS28). In addition to quantify blood and salivary levels of the biomarkers RANKL, OPG, RANKL / OPG, Survivina, and cyclic citrullinated anti-peptide antibodies (ACPAs) and anti-carbamylates (Anti-CarP). Methods: The study sample consisted of a total of 471 individuals randomly divided into groups, according to the objective of each study. The clinical trial performed the following assessments at baseline (T1) and 45 days (T2) after TPNC: periodontal examinations of full mouth, microbiological analysis using real-time qPCR, assessments of the Disease Activity Score (DAS-28). In addition, the quantification of biomarkers and Anti-Carp antibodies and ACPAs performed by ELISA in serum / saliva. Results: The present study reported a high prevalence of PE in individuals with RA and an important association between the occurrence, severity and extent of PE associated with RA and smoking. The non-surgical periodontal treatment was effective in improving the clinical periodontal condition, reduced the presence of the periodontal pathogens evaluated and improved the clinical picture of RA (reduced DAS-28 scores). Additionally, it reduced the levels of survivin, RANKL and concentration of ACPAs and Anti-CarP. Conclusion: Our findings corroborate the robustness of the scientific evidence on the association between periodontitis and RA. Thus, the control of periodontal infection in patients with RA and PE can be an important therapeutic tool in the control of RA.

Surrogate endpoints: when to use and when not to use? A critical appraisal of current evidences

Abstract Clinical research needs to formulate a question, which must be answered by obeying ethical precepts with well-defined inclusion/exclusion criteria and approval of the study on platforms of ethical appreciation and clinical trial records. In comparing the results or clinically relevant outcomes should be prioritized in the study of techniques, products, inputs, drugs and therapies. However, it is not always possible to use long study drawings, with many participants, and with many costs, then look for study designs with surrogate outcomes, usually a shorter path, with less sample size and considerably lower costs to the research, with shorter intervention time. Considering these outcomes as major challenges in clinical research, the premise of this work was to examine in relevant research platforms, studies on the feasibility of using surrogate endpoints for clinically relevant parameters in dentistry, with a critical evaluation of the advantages, disadvantages, and need for validation of substitute parameters for clinical studies. After a critical analysis of the results, it could be concluded that surrogate endpoints may have an important role in the initial process of developing new drugs, faster, with less sampling, and lower risk of side effects for the patient. Careful use of the surrogate endpoints is advised because, even if validated, they can provide ambiguous evidence and not be extrapolated to other populations, and may lead to bias due to the individual interpretation of each researcher. The use of unplanned surrogate outcomes that arise during the study requires a lot of caution.

Stress hormones promote DNA damage in human oral keratinocytes / Hormônios do estresse promovem dano no DNA de queratinócitos humanos de boca

O estresse crônico aumenta os níveis sistêmicos dos hormônios do estresse norepinefrina e cortisol. Assim como o carcinógeno específico do tabaco NNK (4- (metilnitrosamina)-1-(3-piridil)-1-butanona), estes hormônios podem induzir danos expressivos no DNA, o que contribui para o desenvolvimento do câncer. No entanto, é desconhecido se os hormônios do estresse possuem efeitos genotóxicos em queratinócitos de boca. Este estudo investigou os efeitos dos hormônios do estresse sobre o dano no DNA de uma linhagem celular de queratinócitos humanos de boca (NOK-SI). Células NOK-SI estimuladas com norepinefrina ou cortisol apresentaram maior dano no DNA que as células não tratadas. O dano induzido pela norepinefrina foi revertido pelo pré-tratamento das células com um beta-bloqueador. Células tratadas com NNK combinado à norepinefrina apresentaram níveis reduzidos das caspases 3 e 7. O cortisol também reduziu a atividade das enzimas pro-apoptóticas em relação às células não estimuladas. O dano no DNA promovido pelo NNK e cortisol e pela combinação de ambos levou ao acúmulo de γH2AX intracelular. Os efeitos causados pelo NNK e cortisol foram bloqueados com propranolol e com o antagonista do receptor de glicorcorticoide RU486, respectivamente. As quebras no DNA induzidas pela norepinefrina, na presença ou ausência de NNK, resultaram em maiores níveis celulares de 8OHdG. Este efeito também foi induzido via receptores beta-adrenérgicos. Os hormônios do estresse induzem danos no DNA de queratinócitos de boca e poderiam contribuir para a carcinogênese bucal(AU)

Chronic stress increases the systemic levels of stress hormones norepinephrine and cortisol. As well tobacco-specific carcinogen NNK (4-(methylnitrosamine)-1-(3- pyridyl)-1-butanone), they can induce expressive DNA damage contributing to the cancer development. However, it is unknown whether stress hormones have genotoxic effects in oral keratinocytes. This study investigated the effects of stress hormones on DNA damage in a human oral keratinocyte cell line (NOK-SI). NOK-SI cells stimulated with norepinephrine or cortisol showed higher DNA damage than untreated cells. Norepinephrine-induced DNA damage was reversed by pretreatment with beta-adrenergic blocker propranolol. Cells treated with NNK combined to norepinephrine displayed reduced levels of caspases 3 and 7. Cortisol also reduced the activity of pro-apoptotic enzymes. DNA damage promoted by NNK or cortisol and carcinogen combined to the hormone led to intracellular γH2AX accumulation. The effects caused by NNK and cortisol were abolished by propranolol and glucocorticoid receptor antagonist RU486, respectively. DNA breaks induced by norepinephrine in the presence or absence of NNK resulted in higher 8OHdG cellular levels. This effect was also induced through beta-adrenergic receptors. Stress hormones induce DNA damage of oral keratinocytes and could contribute to oral carcinogenesis(AU)

Preliminary findings on the possible role of B-lymphocyte stimulator (BLyS) on diabetes-related periodontitis

Abstract The possible role of B-cell growth and differentiation-related cytokines on the pathogenesis of diabetes-related periodontitis has not been addressed so far. The aim of this study was to evaluate the effects of diabetes mellitus (DM) on the gene expression of proliferation-inducing ligand (APRIL) and B-lymphocyte stimulator (BLyS), two major cytokines associated to survival, differentiation and maturation of B cells in biopsies from gingival tissue with periodontitis. Gingival biopsies were obtained from subjects with periodontitis (n = 17), with periodontitis and DM (n = 19) as well as from periodontally and systemically healthy controls (n = 10). Gene expressions for APRIL, BLyS, RANKL, OPG, TRAP and DC-STAMP were evaluated using qPCR. The expressions APRIL, BLyS, RANKL, OPG, TRAP and DC-STAMP were all higher in both periodontitis groups when compared to the control group (p < 0.05). Furthermore, the expressions of BLyS, TRAP and RANKL were significantly higher in the subjects with periodontitis and DM when compared to those with periodontitis alone (p < 0.05). The mRNA levels of BLyS correlated positively with RANKL in the subjects with periodontitis and DM (p < 0.05). BLyS is overexpressed in periodontitis tissues of subjects with type 2 DM, suggesting a possible role of this cytokine on the pathogenesis DM-related periodontitis.

Impacto do tratamento periodontal não cirúrgico nos níveis de biomarcadores do metabolismo ósseo na saliva / Non-surgical periodontal treatment impact on biomarkers levels of bone metabolism in saliva

O objetivo foi avaliar o efeito do tratamento periodontal não cirúrgico, após 1 ano, na expressão salivar dos marcadores do metabolismo ósseo: TNF-α, SOST, PTH, OPG, OPN, OC, Leptina, IL-6, IL-1ß e FGF-23; em pacientes com periodontite crônica generalizada. Participaram deste estudo 15 pacientes com periodontite crônica generalizada (idade média 56,0  DP 9,6 anos). Quinze pacientes com gengivite (idade média 39,7  DP 4,4 anos) foram utilizados como controles. Foram utilizados os seguintes parâmetros clínicos: profundidade de bolsa à sondagem (PBS); nível de inserção clínica (NIC); índice de placa visível (IPV); índice de sangramento gengival (ISG) e índice de sangramento à sondagem (ISS). Foi realizada a coleta de saliva não estimulada (1ml) e congelada à -70°C para posterior análise. Os pacientes de ambos os grupos receberam tratamento periodontal não cirúrgico. Todos os dados foram coletados em 3 visitas no grupo com periodontite (baseline, 6 meses e 1 ano); e em 2 visitas no grupo com gengivite (baseline e 1 ano). Os biomarcadores foram mensurados por meio de um imunoensaio multiplex. No grupo com periodontite, houve redução significativa dos parâmetros % PBS ≥ 6 (p<0,001) e % NIC ≥ 5 (p<0,001), nas visitas 6 meses e 1 ano. Para os dados clínicos do grupo com gengivite, houve diminuição significativa após 1 ano para: % placa (p=0,001), % sangramento marginal (p=0,001), % sangramento sondagem (p=0,001), PBS (média pac.) (p=0,020) e NIC (média pac.) (p=0,001). Após o tratamento no grupo com periodontite, observou-se redução significativa da IL-1ß, IL-6, Leptina e TNF-α, entre a visita baseline e 6 meses (p=0,006; p=0,050; p=0,047; p= 0,014; respectivamente). Entre o baseline e 1 ano, houve diferença significante para a IL-1ß (p=0,010) e OPG (p=0,050). Já a IL-6 e OPG, mostraram uma tendência a redução após 1 ano (p=0,074; p=0,063; respectivamente). No grupo com gengivite, não foram observadas diferenças significativas entre as visitas baseline e 1 ano para todos os biomarcadores. No grupo com periodontite, na visita 1 ano, observamos correlação negativa significativa da OPG com % sangramento sondagem ( τ-b = -0,524 / p=0,006); no grupo com gengivite, na visita baseline, observamos correlação positiva significativa da IL-6 com % placa (τ-b= 0,548 / p= 0,005). Já na visita 1 ano, a Leptina passou a se correlacionar de forma mais forte com % placa (τ-b=0,624 / p=0,010) e com % sangramento marginal (τ-b=0,751 / p= 0,001). Concluindo, a terapia periodontal não cirúrgica levou a uma melhora significativa dos parâmetros clínicos periodontais associada à uma redução significante nos níveis de TNF-α, Leptina e IL-1ß; e uma tendência à redução dos biomarcadores OPG e IL-6. Após 1 ano, verificamos que os níveis dos biomarcadores do grupo com periodontite se aproximaram aos valores do grupo com gengivite, sugerindo que o tratamento periodontal foi capaz de equalizar a resposta imunológica.

The aim of this study was to evaluate the effect of non-surgical periodontal therapy, after 1 year, on the salivar expression of bone metabolism markers: TNF-α, SOST, PTH, OPG, OPN, OC, Leptin, IL-6, IL-1ß and FGF-23; in patients with generalized chronic periodontitis. Fifteen patients with generalized chronic periodontitis (mean age 56.0 ± SD 9.6 years) were included in this study. Fifteen patients with gingivitis (mean age 39.7 ± SD 4.4 years) were used as controls. Clinical evaluation parameters including probing pocket depth (PD), clinical attachment level (CAL), visible plaque index (VPI), gingival index bleeding (GI) and bleeding on probing (BOP) were used. Non-stimulated whole saliva was collected (1ml) and frozen at -70°C for further analysis. Patients from both groups received non-surgical periodontal treatment. All data were collected in 3 visits in the group with periodontitis (baseline, 6 months and 1 year); and in 2 visits in the group with gingivitis (baseline and 1 year). The biomarkers expression were evaluated through multiplex technology. In the group with periodontitis, there was a significant reduction of the parameters % PD ≥ 6 (p <0,001) and % CAL ≥ 5 (p <0,001), at 6 months and 1 year visits. For the clinical data of the group with gingivitis, there was a significant decrease after 1 year for: plaque (p=0,001), sulcus bleeding (p=0,001), bleeding on probing (p=0,001), PD (p=0,020) and CAL (p=0,001). After treatment in the group with periodontitis, a significant reduction of IL-1ß, IL-6, Leptin and TNF-α was observed between baseline and 6 months visit (p=0,006; p=0,050; p=0,047; p=0,014; respectively). Between baseline and 1 year, there was significant difference for IL-1ß (p=0,010) and OPG (p=0,050). On the other hand, IL-6 and OPG showed a tendency to decrease after 1 year (p=0,074; p=0,063; respectively). In the group with gingivitis, no significant differences were observed between the baseline visits and 1 year for all biomarkers. In the group with periodontitis, at the 1-year visit, we observed a significant negative correlation of OPG with bleeding on probing (τ-b=-0,524 / p=0,006); in the group with gingivitis, at the baseline visit, we observed a significant positive correlation of IL-6 with plaque (τ-b=0,548 / p=0,005). At the 1-year visit, Leptin correlated more strongly with plaque (τ-b=0,624 / p=0,010) and with sulcus bleeding (τ-b=0,751 / p=0,001). In conclusion, non-surgical periodontal therapy led to a significant improvement in periodontal clinical parameters associated with a significant reduction in levels of TNF-α, Leptin and IL-1ß; the OPG and IL-6 showed a tendency to reduce. After 1 year, we observed that the biomarkers levels in the group with periodontitis approximate the values of the group with gingivitis, suggesting that the periodontal treatment was able to equalize the immune response.

The role of visfatin levels in gingival crevicular fluid as a potential biomarker in the relationship between obesity and periodontal disease

Abstract Objectives Visfatin is an adipokine that plays an important role in immune functions as a growth factor, enzyme, and pro-inflammatory mediator. We aimed to determine the levels of visfatin, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in gingival crevicular fluid (GCF) in both obese/non-obese patients, with/without generalized chronic periodontitis (GCP). Methodology Patients were categorized as obese (O) (n=31) or non-obese (nO) (n=19). Groups were divided into four subgroups according to periodontal conditions: (1) periodontally healthy without obesity (nO-Ctrl); (2) GCP without obesity (nO-CP); (3) periodontally healthy with obesity (O-Ctrl); and (4) GCP with obesity (O-CP). Demographic variables, anthropometric and laboratory data were recorded. Periodontal parameters were measured at baseline and 3rd months after either non-surgical periodontal treatment or calorie -restricted diet therapy. At the same time, GCF samples were taken from patients to analyze TNF-alpha, IL-6,and visfatin levels. Results Periodontal parameters were significantly higher in the O group than in the nO group (P<0.05). IL-6 levels were higher in the O group than in the nO group (P<0.001). The visfatin levels of the obese patients were reduceddecreased following the treatments (P<0.05). Cholesterol levels were higher in the O group than in the nO groups (P<0.05). IL-6 levels were higher in O-CP and O-Ctrl groups than in the nO-Ctrl group (P<0.05). Compared to the other groups, visfatin levels were significantly higher in the O-CP group but decreased following treatment (P<0.05). Conclusions Our findings suggest that visfatin and IL-6 levels in GCF are associated with the pathogenesis of obesity and periodontitis. Within the limits of this study, we considered that there might be an association between the lipid profile and periodontitis on systemically healthy individuals.

Clinical attachment loss and molecular profile of inflamed sites before treatment

Abstract Objective: To monitor early periodontal disease progression and to investigate clinical and molecular profile of inflamed sites by means of crevicular fluid and gingival biopsy analysis. Methodology: Eighty-one samples of twenty-seven periodontitis subjects and periodontally healthy individuals were collected for the study. Measurements of clinical parameters were recorded at day −15, baseline and 2 months after basic periodontal treatment aiming at monitoring early variations ofthe clinical attachment level. Saliva, crevicular fluid and gingival biopsies were harvested from clinically inflamed and non-inflamed sites from periodontal patients and from control sites of healthy patients for the assessment of IL-10, MMP-8, VEGF, RANKL, OPG and TGF-β1 protein and gene expression levels. Results: Baseline IL-10 protein levels from inflamed sites were higher in comparison to both non-inflamed and control sites (p<0.05). Higher expression of mRNA for IL-10, RANK-L, OPG, e TGF-β1 were also observed in inflamed sites at day −15 prior treatment (p<0.05). After the periodontal treatment and the resolution of inflammation, seventeen percent of evaluated sites still showed clinically detectable attachment loss without significant differences in the molecular profile. Conclusions: Clinical attachment loss is a negative event that may occur even after successful basic periodontal therapy, but it is small and limited to a small percentage of sites. Elevated inflammation markers of inflamed sites from disease patients reduced to the mean levels of those observed in healthy subjects after successful basic periodontal therapy. Significantly elevated both gene and protein levels of IL-10 in inflamed sites prior treatment confirms its modulatory role in the disease status.