Relação entre a doença periodontal e a doença de Alzheimer - Revisão da Literatura / Relationship between periodontal disease and Alzheimer disease ­ literature review

O objetivo do presente estudo foi revisar a literatura para buscar evidências na associação entre a doença de Alzheimer e a Periodontite. A metodologia usada resultou numa busca às bases de dados PubMed/MEDLINE, Cochrane Library e Web of Science, através dos artigos publicados entre o período de maio de 2000 a maio de 2022. A doença de Alzheimer (DA) é classificada como uma condição neurodegenerativa, um grupo heterogêneo de doenças caracterizadas pela perda lenta e progressiva de uma ou mais funções do sistema nervoso. A doença periodontal (DP) é uma doença infecciosa e inflamatória que causa principalmente destruição óssea alveolar e perda dentária e estima-se que entre 20 e 50% da população geral possa sofrer de DP, dos quais 15-20% apresentam formas graves. A inflamação desempenha um papel crítico no aparecimento e progressão de ambas as doenças. A conclusão desta revisão é que a literatura estudada mostra que os patógenos periodontais e as citocinas pró-inflamatórias contribuíram para a progressão do processo neurodegenerativo da doença de Alzheimer. Porém, são necessários mais estudos clínicos controlados randomizados para a confirmação da relação causal desta associação.

The aim of this study was to review the literature to look for evidence in the association between Alzheimer's disease and Periodontitis. The methodology used resulted in a search of the PubMed/MEDLINE, Cochrane Library and Web of Science databases, through the articles published between May 2000 and May 2022. Alzheimer's disease (AD) is classified as a neurodegenerative condition, a heterogeneous group of diseases characterized by the slow and progressive loss of one or more functions of the nervous system. Periodontal disease (PD) is an infectious and inflammatory disease that mainly causes alveolar bone destruction and tooth loss and it is estimated that between 20 and 50% of the general population may suffer from PD, of which 15-20% present severe forms. Inflammation plays a critical role in the onset and progression of both diseases. The conclusion of this review is that the literature studied shows that periodontal pathogens and pro-inflammatory cytokines contributed to the progression of the neurodegenerative process of Alzheimer's disease. However, more randomized controlled clinical trials are needed to confirm the causal relationship of this association.

Associação entre marcadores inflamatórios e o padrão locomotor durante a ultrapassagem de obstáculos em idosos / Association between inflammatory markers and locomotor pattern during obstacle avoidance in older adults

Resumo Objetivo investigar a associação dos biomarcadores inflamatórios na tarefa de ultrapassagem de obstáculos com diferentes níveis de complexidade manipulados pela característica do obstáculo (sólido e frágil) em idosos. Método 17 idosos (≥60 anos) foram avaliados em dois momentos: 1) Análise do padrão locomotor durante a ultrapassagem de obstáculo em duas condições (sólido e frágil). As variáveis estudadas, para membros de abordagem e suporte foram: velocidade, comprimento, largura e duração da passada, distância horizontal pé-obstáculo, distância horizontal obstáculo-pé, distância vertical pé-obstáculo e Máxima elevação do pé. 2) A análise dos biomarcadores interleucina 6 (IL-6) e proteína C Reativa (PCR) foi realizada por meio de coleta de sanguínea. A análise de regressão linear múltipla foi realizada para verificar associação entre o padrão locomotor e os biomarcadores inflamatórios (IL-6 e PCR) com nível de significância de p≤0,05. Resultados A análise de regressão mostrou que a Interleucina 6 apresentou associação com as seguintes variáveis: 1) largura da passada na condição obstáculo sólido, 2) máxima elevação do pé (membro de suporte) para ultrapassagem do obstáculo frágil, 3) distância horizontal pé-obstáculo (membro de abordagem) na condição de obstáculo sólido, 4) máxima elevação do pé (membro de abordagem) para ultrapassagem do obstáculo frágil, 5) máxima elevação do pé (membro de abordagem) para ultrapassagem do obstáculo sólido. A PCR apresentou associação com a variável Distância Horizontal Pé-Obstáculo (membro de abordagem) apenas para a condição de obstáculo frágil. Conclusão Os biomarcadores inflamatórios apresentam uma associação com o comportamento locomotor em idosos, independente da condição de fragilidade do obstáculo.

Abstract Objective to investigate the association of inflammatory biomarkers on the locomotor pattern during obstacle avoidance with different levels of complexity manipulated by the characteristic of the obstacle (solid and fragile) in older adults. Method 17 older adults (≥60 years old) were evaluated in two moments: 1) Analysis of the locomotor pattern during obstacle crossing in two conditions (solid and fragile). The variables studied for trailing and leading limbs were: speed, length, width and duration of the stride, horizontal foot-obstacle distance, horizontal obstacle-foot distance, vertical foot-obstacle distance and Maximum foot elevation. 2) Blood collection, for analysis of the inflammatory biomarkers Interleukin 6 (IL6) and C-Reactive Protein (CRP). Multiple linear regression analysis was performed to verify association between locomotor pattern and inflammatory biomarkers (IL6 and CRP) with a significance level of p≤0.05. Results The regression analysis showed that Interleukin 6 was associated with the following variables: 1) stride width in the solid obstacle condition, 2) maximum foot elevation (leading limb) to avoidance the fragile obstacle, 3) horizontal foot-obstacle distance (trailing limb) in solid obstacle condition, 4) maximum foot elevation (trailing limb) to avoidance the fragile obstacle, 5) maximum foot elevation (trailing limb) to avoidance the solid obstacle. C-Reactive Protein was associated with the horizontal foot-obstacle distance (trailing limb) only for the fragile obstacle condition. Conclusion Inflammatory biomarkers are associated with the locomotor pattern in older adults, regardless of the fragility of the obstacle.

Biomarcadores inflamatorios en líquido sinovial de trastornos intraarticulares de la articulación temporomandibular. Revisión sistemática / Inflammatory biomarkers in synovial fluid of intra-articular disorders of the temporomandibular joint. Systematic review

RESUMEN Objetivo: Determinar los biomarcadores inflamatorios del líquido sinovial (LS) de pacientes adultos con trastornos intraarticulares (TI) de la articulación temporomandibular (ATM) y su capacidad diagnóstica. Métodos: Se realizó búsqueda electrónica/manual de artículos (2010-2019) en paralelo por dos investigadores. La calidad de los estudios, se determinó por medio de CONSORT y STROBE y el sesgo según criterios Cochrane RoB 2 en ensayos clínicos aleatorizados y Escala Newcastle-Ottawa en estudios observacionales. Se estudiaron pacientes con TI de la ATM y determinación de biomarcadores del LS. Resultados: De 264 artículos encontrados, 6 cumplieron los criterios inclusión-exclusión, incluyendo 262 pacientes, [OA=153, 93 con desplazamientos discales (DD) y 16 con OA+DD]. Todas las muestras fueron obtenidas por artrocentesis y detectadas por ELISA. Se determinaron 19 biomarcadores en pacientes con OA; 9 en DD y 2 en diagnosticados con OA+DD. El incremento de biomarcadores en el LS de la ATM se asocia con TI. Conclusión: Los biomarcadores detectados con mayor frecuencia en LS de pacientes con TI de ATM fueron IL-1β, IL-6 y TNF-α y en segunda frecuencia TGF-β1, MMP-3 e IFN-γ. Dada la inconsistencia de los protocolos utilizados la evidencia fue débil, imposibilitando asociar biomarcadores con diagnóstico de TI determinado, ni efectuar análisis estadístico.

ABSTRACT: Objective: To determine the evidence of inflammatory biomarkers present in the synovial fluid (SF) of adult patients with intra-articular disorders (ID) of the temporomandibular joint (TMJ) and their diagnostic ability. Methods: Electronic/manual search of articles (2010-2019) was performed. Data were extracted in duplicate. The quality of the studies was determined by CONSORT, STROBE and risk of bias was determined by Cochrane RoB 2 and Newcastle-Ottawa Scale. The populations studied were patients with TMJ ID and with studies of SF biomarkers. Results: Out of 264 articles found, 6 met the inclusion-exclusion criteria, including 262 patients, 93 with disc displacements (DD) and 16 with OA+DD. All samples were obtained by arthrocentesis and detected by ELISA. Nineteen biomarkers were evaluated in patients with OA, 9 in patients with DD and 2 in those diagnosed with OA+DD. Increased inflammatory biomarkers in the SF of TMJ are associated with ID. Conclusion: The most frequent biomarkers detected in SF of patients with TMJ ID were IL-1β, IL-6 and TNF-α and in second frequency TGF-β1, MMP-3 and IFN-γ. Given the inconsistency of the protocols used, the evidence was weak, making it impossible to associate biomarkers with a given IT diagnosis, or to perform statistical analysis.

Inflammatory Markers in the Staging of Bipolar Disorder: A Systematic Review of the Literature / Marcadores inflamatorios en la estadificación del trastorno bipolar: una revisión sistemática de la literatura

ABSTRACT Background: Previous studies suggest that inflammatory molecules play an important role in the pathophysiology of Bipolar Disorder (BD). The evidence suggests that BD may present a progressive course. Therefore there are theories that postulate the relationship between progression and stages of the disease with distinct peripheral biomarkers. Objective: The aim of this study was to carry out a systematic review of the literature of studies about the association between peripheral inflammatory markers and clinical variables related with staging in BD patients. Methods: We conducted a systematic review using electronic databases: PubMed, SciELO, LiLACS and PsycINFO. Keywords were divided into inflammatory markers and, BD and staging. Studies involving euthymic BD patients, studies evaluating peripheral biomarkers and studies correlating these with clinical variables related to neuroprogression or stage of BD were included. Results: We present and discuss the methods and findings of ten articles. The inflammatory markers were measured with different techniques and show some contradictories results. The TNF superfamily and inflammatory cytokines may have a relationship with the neuroprogression of the disease. Conclusions: This study suggests that TNF and ILs could play a role in neuroprogression. However, longitudinal studies are needed to clarify the relationship between factors associated with neuroprogression.

RESUMEN Introducción: Estudios previos indican que las moléculas inflamatorias tienen un papel importante en la fisiopatología del trastorno bipolar (TB). La evidencia apunta a que el TB puede presentar un curso progresivo. Por lo tanto, existen teorías que han postulado una relación entre la progresión y los estadios de la enfermedad con diferentes biomarcadores Revisión sistemática periféricos. Objetivo: El objetivo de este estudio es realizar una revisión sistemática de la literatura de los estudios sobre la asociación entre los marcadores inflamatorios periféricos y las variables clínicas relacionadas con la estadificación en los pacientes con TB. Métodos: Se llevó a cabo una revisión sistemática usando las bases de datos electrónicas PubMed, SciELO, LiLACS y PsycINFO. Las palabras clave se dividieron en marcadores inflamatorios y TB y estadificación. Se incluyeron estudios que evaluaron a pacientes con TB en fase de eutimia, estudios que evaluaron biomarcadores periféricos y estudios que correlacionaron dichos marcadores con las variables clínicas relacionadas con la neuroprogresión o estadificación del TB. Resultados: Se presentan y se discuten los métodos y los hallazgos de 10 artículos. Los marcadores inflamatorios se determinaron con diferentes técnicas y mostraron resultados contradictorios. La super familia del factor de necrosis tumoral y las citocinas inflamatorias podrían tener una relación con la neuroprogresión de la enfermedad. Conclusiones: El presente estudio indica que el factor de necrosis tumoral y las intereucinas pueden tener un papel en la neuroprogresión del TB. Sin embargo, se requieren estudios longitudinales con el fin de clarificar la relación entre los factores asociados con la neuro-progresión.

Inflammatory Markers in the Staging of Bipolar Disorder: A Systematic Review of the Literature.

BACKGROUND: Previous studies suggest that inflammatory molecules play an important role in the pathophysiology of Bipolar Disorder (BD). The evidence suggests that BD may present a progressive course. Therefore there are theories that postulate the relationship between progression and stages of the disease with distinct peripheral biomarkers. OBJECTIVE: The aim of this study was to carry out a systematic review of the literature of studies about the association between peripheral inflammatory markers and clinical variables related with staging in BD patients. METHODS: We conducted a systematic review using electronic databases: PubMed, SciELO, LiLACS and PsycINFO. Keywords were divided into inflammatory markers and, BD and staging. Studies involving euthymic BD patients, studies evaluating peripheral biomarkers and studies correlating these with clinical variables related to neuroprogression or stage of BD were included. RESULTS: We present and discuss the methods and findings of ten articles. The inflammatory markers were measured with different techniques and show some contradictories results. The TNF superfamily and inflammatory cytokines may have a relationship with the neuroprogression of the disease. CONCLUSIONS: This study suggests that TNF and ILs could play a role in neuroprogression. However, longitudinal studies are needed to clarify the relationship between factors associated with neuroprogression.

Quercetin inhibits chronic stress-induced myocardial infarction in rats / La quercetina inhibe el infarto al miocardio inducido por estrés crónico en ratas

RESUMEN: Reportamos recientemente que el estrés crónico súbito (ECS) induce disfunción ventricular izquierda (DVI) en ratas, la que fue inhibida por la quercetina un agente cardioprotector. En base de estos hallazgos y debido a que la mayoría de los pacientes con infarto de miocardio (IM) pueden desarrollar DVI e insuficiencia cardíaca, se buscó producir un modelo animal de IM y DVI en ratas, utilizando este modelo para probar la hipótesis de que la quercetina puede prevenir la inducción potencial de IM por ECS. Las ratas fueron expuestas a ECS usando una variedad de factores de estrés de quercetina (50 mg / kg de peso corporal / día) durante 21 días. Se registró la presión sanguínea y el electrocardiograma (ECG) en todos los grupos de ratas junto con el examen de homogeneizados de tejido del ventrículo izquierdo (VI) y secciones para confirmar la producción del modelo animal. Asociamos los recientes hallazgos sobre el papel de la apoptosis en la patología de DVI y, finalmente, IM. Las mediciones de la presión arterial y la grabación de ECG confirmaron el desarrollo de hipertensión sistémica y del IM en el grupo modelo de ratas expuestas a ECS. Además, la tinción histológica confirmó que el daño del VI se produjo en el mismo grupo. Tambien se obervó un aumento del gen proapoptótico Bax y de los biomarcadores inflamatorios, TNF-α e IL-6. El tratamiento simultáneo con quercetina redujo la presión sanguínea y evitó sustancialmente el IM, bloqueando el aumento del segmento ST en el ECG. Por lo tanto, el IM inducido por ECS en ratas asociado con el aumento de los biomarcadores de lesión tisular, fueron impedidos por la quercetina, lo que concuerda con nuestros hallazgos recientes de un posible papel terapéutico de la quercetina en la disfunción cardíaca inducida por ECS.

SUMMARY: We recently reported that chronic unpredictable stress (CUS) induced left ventricular dysfunction (LVD) in rats, which was inhibited by the cardioprotective agent quercetin. Based on these findings and because majority of patients with myocardial infarction (MI) can develop LVD and heart failure, we sought to produce an animal model of MI and LVD in rats and use this model to test the hypothesis that quercetin is able to prevent the potential MI induction by CUS. Rats were exposed to CUS using a variety of stressors in the presence and absence of quercetin (50 mg/kg body weight/day) for 21 days. Blood pressure and electrocardiogram (ECG) were recorded in all rat groups together with the examination of left ventricle (LV) tissue homogenates and sections to confirm the production of the animal model. We further extend on our recent findings on the role of apoptosis in the pathology of LVD and eventually MI. Blood pressure measurements and ECG recording confirmed the development of systemic hypertension and MI in the model group of rats exposed to CUS. In addition, histological staining confirmed that LV damages occurred in the same group. Furthermore, the proapoptotic gene Bax and the inflammatory biomarkers, TNF-α and IL-6 were augmented in LV homogenates by CUS. Simultaneous quercetin treatment lowered blood pressure and substantially prevented MI since it blocked the elevation of ST segment on the ECG and maintained a normal ECG reading. Quercetin suppressed the expression of Bax RNA messages, and significantly (p<0.05) blocked CUS-induced TNF-α and IL-6 upregulation. Thus, CUS induced MI in rats associated with augmentation of tissue injury biomarkers were prevented by quercetin, which further endorses our recent findings of a potential therapeutic role for quercetin in CUS induced cardiac dysfunction.