Modulating the sEH/EETs Axis Restrains Specialized Proresolving Mediator Impairment and Regulates T Cell Imbalance in Experimental Periodontitis.

Epoxyeicosatrienoic acids (EETs) and other epoxy fatty acids are short-acting lipids involved in resolution of inflammation. Their short half-life, due to its metabolism by soluble epoxide hydrolase (sEH), limits their effects. Specialized proresolving mediators (SPMs) are endogenous regulatory lipids insufficiently synthesized in uncontrolled and chronic inflammation. Using an experimental periodontitis model, we pharmacologically inhibited sEH, examining its impact on T cell activation and systemic SPM production. In humans, we analyzed sEH in the gingival tissue of periodontitis patients. Mice were treated with sEH inhibitor (sEHi) and/or EETs before ligature placement and treated for 14 d. Bone parameters were assessed by microcomputed tomography and methylene blue staining. Blood plasma metabololipidomics were carried out to quantify SPM levels. We also determined T cell activation by reverse transcription-quantitative PCR and flow cytometry in cervical lymph nodes. Human gingival samples were collected to analyze sEH using ELISA and electrophoresis. Data reveal that pharmacological sEHi abrogated bone resorption and preserved bone architecture. Metabololipidomics revealed that sEHi enhances lipoxin A4, lipoxin B4, resolvin E2, and resolvin D6. An increased percentage of regulatory T cells over Th17 was noted in sEHi-treated mice. Lastly, inflamed human gingival tissues presented higher levels and expression of sEH than did healthy gingivae, being positively correlated with periodontitis severity. Our findings indicate that sEHi preserves bone architecture and stimulates SPM production, associated with regulatory actions on T cells favoring resolution of inflammation. Because sEH is enhanced in human gingivae from patients with periodontitis and connected with disease severity, inhibition may prove to be an attractive target for managing osteolytic inflammatory diseases.

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

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.

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.

Relação entre função cognitiva e capacidade funcional em idosos institucionalizados de Caxias do Sul/RS / Relationship between cognitive function and functional capacity in institutionalized elderly of Caxias do Sul/RS

O envelhecimento normal engloba um declínio gradual nas funções cognitivas, dependentes de processos neurológicos quese alteram com a idade. O declínio que acompanha o idoso tem início e progressão extremamente variáveis, e a perda de memória aparece como uma das funções mais acometidas. O objetivo deste estudo foi caracterizar uma população de idosos institucionalizados de Caxias do Sul/RS quanto ao seu estado cognitivo, às atividades comuns de vida diária, à mobilidade e à autonomia funcional a fim de identificar possível associação existente entre déficit cognitivo e prejuízo motor decorrentes da institucionalização destes sujeitos e vice-versa. Participaram deste estudo 67 sujeitos (77,59 ± 8 anos),os quais foram submetidos ao teste cognitivo Mini-Exame do Estado Mental (MEEM). Mobilidade para membros superiores e inferiores,e as atividades de vida diária foram avaliadas através do Índice de Katz. Não foi encontrada correlação estatisticamente significativa entre MEEM e idade, gênero, escolaridade e mobilidade de membros inferiores (r = 0,02, p > 0,05, Pearson). Uma associação foi detectada entre o desempenho dos idosos no teste para mobilidade dos membros superiores e o teste cognitivo MEEM (p = 0,01 e r= 0,251 Pearson). Os idosos demonstraram um déficit significativo na realização das tarefas banho, vestuário e transferência através do Índice de Katz. Portanto, podemos concluir através deste estudo que as alterações cognitivas detectadas através do MEEM não tiveram associação com o desempenho dos idosos nos testes de mobilidade para membros inferiores. Entretanto, verificou-se uma associação significativa entre o desempenho dos idosos no teste de capacidade funcional para membros superiores e o teste cognitivo avaliado através do MEEM.

Normal aging involves a gradual decline in cognitive abilitieswhich are dependent on neurological processes that change withage. The decline accompanying the elderly is extremely variable inrelation to initiation and progression, and memory loss is one of themost affected functions. The aim of this study was to characterize a population of institutionalized elderly people of the city of Caxias do Sul/RS concerning their cognitive state, common activitiesof daily living, mobility and functional autonomy, in order toidentify possible association between cognitive deficit and motor impairment as a result of institutionalization of these subjects and vice-versa. Sixty-seven subjects (77.59 ± 8 years old) participated onthis study, and underwent cognitive testing using the Mini-MentalState Examination (MMSE). Mobility of upper and lower limbsand activities of daily life were evaluated using the Katz Index. Nostatistically significant correlation was found between MMSE withage, gender, education and mobility of lower limbs (r = 0.02, p >0.05, Pearson). Association was detected between the performance of the elderly in the mobility test of the upper limbs and cognitivetest MMSE (p = 0.01 e r = 0.251 Pearson). The Katz Index showed that the elderly had a significant deficit in performing the following tasks: bathing, clothing and transfer. Therefore, we conclude thatthe cognitive impairments of these elderly people, detected via theMMSE, did not have any association with their performance in thetest of lower limbs mobility. How ever, it was found a significant association between the performance of the elderly in the upperlimbs functional capacity test and the assessment of cognitive function using the MMSE