الملخص
Stem cells are undifferentiated cells that can be distinguished from others by their ability to self-renew and to differentiate into new specific cell types. Mesenchymal stem cells (MSC) are adult stem cells that can be obtained from different sources, such as adipose tissue, bone marrow, dental pulp, and umbilical cord. They can either replicate, originating new identical cells, or differentiate into cells of mesodermal origin and from other germ layers. MSC have been studied as new tools for regenerative therapy. Although encouraging results have been demonstrated, MSC-based therapies still face a great barrier: the difficulty of isolating these cells from heterogeneous environments. MSC are currently characterized by immunolabelling through a set of multiple surface membrane markers, including CD29, CD73, CD90 and CD105, which are also expressed by other cell types. Hence, the present work aimed to identify new specific biomarkers for the characterization of human MSC using DNA aptamers produced by the SELEX (Systematic Evolution of Ligands by EXponential Enrichment) technique. Our results showed that MSC from different origins bound to DNA candidate aptamers, that is, DNA or RNA oligonucleotides selected from random libraries that bind specifically to biological targets. Aptamer-bound MSC could be isolated by fluorescenceactivated cell sorting (FACS) procedures, enhancing the induction of differentiation into specific phenotypes (chondrocytes, osteocytes and adipocytes) when compared to the whole MSC population. Flow cytometry analyses revealed that candidate aptamers bound to 50% of the MSC population from dental pulp and did not present significant binding rates to human fibroblasts or lymphocytes, both used as negative control. Moreover, immunofluorescence images and confocal analyses revealed staining of MSC by aptamers localized in the surfacemembrane of these cells. The results also showed internal staining of human monocytes by our investigated aptamers. A non-specific control aptamer (CNTR APT) obtained from the random pool was then utilized to compare the specificity of the aptamers bound to the analyzed non-apoptotic cells, showing no staining for MSC. However, 40% of the monocytes bound to the CNTR APT. Normalized data based on the cells bound to candidate aptamers compared to those bound to the CNTR APT, revealed a 10 to 16-fold higher binding rate for MSC against 2-fold for monocytes. Despite its low specificity, monocyte-aptamer binding occurs probably due to the expression of shared markers with MSC, since monocytes are derived from hematopoietic stem cells and are important for the immune system ability to internalize/phagocyte external molecules. Given that, we performed a pull-down assay followed by mass spectrometry analysis to detect which MSC-specific protein or other target epitope not coexpressed by monocytes or the CNTR APT would bind to the candidate aptamer. Distinguishing between MSC and monocyte epitopes is important, as both cells are involved in immunomodulatory effects after MSC transplantations. ADAM17 was found to be a target of the APT10, emerging as a possible biomarker of MSC, since its involvement in the inhibition of the TGF signaling cascade, which is responsible for the differentiation of MSC. Thus, MSC with a higher stemness profile should overexpress the protein ADAM17, which presents a catalytic site with affinity to APT10. Another target of Apt 10 is VAMP3, belonging to a transmembrane protein complex that is involved in endocytosis and exocytosis processes during immune and inflammatory responses. Overall, proteins identified as targets of APT10 may be cell surface MSC biomarkers, with importance for MSC-based cell and immune therapies
Células tronco são células indiferenciadas que podem ser distinguidas de outros tipos celulares por meio da habilidade de se auto renovarem e de se diferenciarem em novos tipos celulares. Células tronco mesenquimais (MSC) são células tronco adultas encontradas em diferentes tecidos como tecido adiposo, polpa de dente e cordão umbilical. Estas células podem se autodividir em células idênticas ou se diferenciarem em células de origem mesodermal. Estas células têm sido estudadas em novas aplicações que envolvem terapia regenerativas. Embora resultados encorajadores tenham sido demonstrados, terapias que utilizam MSC ainda encontram uma grande barreira: a dificuldade no isolamento destas células a partir de um ambiente heterogêneo. MSC são caracterizadas por populações positivas em ensaios de imunomarcação para os epítopos membranares CD29, CD73, CD90 e CD105, presentes também em outros tipos celulares. Assim, o presente trabalho tem o objetivo de identificar novos biomarcadores de MSC de origem humana, utilizando aptâmeros de DNA produzidos pela técnica SELEX (Systematic Evolution of Ligands by EXponential Enrichment) como ferramenta. Nossos resultados mostraram que MSC de diferentes origens ligam-se a aptâmeros (oligonucleotídeos de DNA ou RNA que atuam como ligantes específicos de alvos moleculares) de DNA candidatos que atuam no isolamento de MSC por meio da técnica FACS de separação celular, promovendo uma maior indução de diferenciação em células específicas (condrócitos, osteócitos e adipócitos) comparada com a população total de MSC. Análises de citometria de fluxo mostraram que os aptâmeros candidatos se ligam a 50% das MSC de polpa de dente e não apresentam taxa de ligação significante para fibroblastos e linfócitos de origem humana - utilizados como controles negativo. Além domais, imagens de imunofluorescência e confocal mostraram ligação na superfície da membrana de MSC e a marcação interna de monócitos a estes aptâmeros. Portanto, um aptâmero controle (CNTR APT) foi utilizado para comparar a especificidade dos aptâmeros ligados a células viáveis, mostrando a não ligação deste aptâmero a MSC. Porém, 40% da população de monócitos ligou-se ao CNTR APT. Uma normalização baseada na comparação entre as taxas de ligação entre células ligadas com aptâmeros candidatos e o aptâmero controle gerou uma taxa de especificidade entre 10-16 vezes maior para MSC contra 2,5 vezes para os monócitos. Deste modo, embora os resultados tenham mostrado uma taxa de ligação entre monócitos e aptâmeros, as MSC ligadas aos aptâmeros candidatos possuem uma maior taxa de especificidade devido a uma maior presença de antígenos que são expressos em ambas as células. Um ensaio de Pull Down seguido de espectrometria de massas foi utilizado para a identificação de biomarcadores que se ligariam aos aptâmeros candidatos, e que não seriam co-expressos por monócitos e por antígenos ligados ao aptâmero controle. Deste modo, a proteína ADAM17 foi identificada nas amostras de APT10 ligadas às MSC. Tal proteína está relacionada à inibição de uma cascata de sinalização da família de proteínas TGF, responsável pela diferenciação de MSC. Assim, MSC com maior potencial tronco deveriam expressar ADAM17 em maior quantidade. Tal proteína apresenta um sítio catalítico que demonstra interagir com o APT10, de acordo com predição Docking entre proteína e DNA. Foi identificada também, a proteína VAMP3, que pertence a um complexo proteico transmembranar responsável pelos processos de endocitose e exocitose, e que podem ter um papel importante na liberação de citocinas e outras moléculas relacionadas às respostas imune e inflamatórias. Deste modo, o APT10 identificou proteínas importantes que devem estar relacionas com a melhora de imunoterapias que utilizam MSC
الموضوعات
Stem Cells , Biomarkers/analysis , SELEX Aptamer Technique/instrumentation , Mesenchymal Stem Cells/classification , ADAM17 Protein/pharmacology , Patient Isolation , Mass Spectrometry/methods , Staining and Labeling/methods , Transplantation/adverse effects , Umbilical Cord , DNA/agonists , Transforming Growth Factors/agonists , Cell Separation/instrumentation , Cytokines/adverse effects , Adipocytes/metabolism , Chondrocytes/classification , Scientists for Health and Research for Development , Adult Stem Cells/classification , Fibroblasts/chemistry , Flow Cytometry/instrumentation , Germ Layers , Antigens/adverse effectsالملخص
Resumo A doença de Behçet constitui uma forma rara de vasculite sistêmica, que acomete de pequenos a grandes vasos. É caracterizada por manifestações mucocutâneas, pulmonares, cardiovasculares, gastrointestinais e neurológicas. Sua apresentação clínica é bastante ampla, variando de casos mais brandos a casos graves, com acometimento multissistêmico, caracteristicamente com exacerbações e remissões. Suas causas ainda são desconhecidas; entretanto, há evidências genéticas, ambientais e imunológicas, como a associação com o alelo HLA-B51. Todas essas, em conjunto, apontam para um processo imunopatológico anormal, com ativação de células da imunidade inata e adaptativa, como as células natural killer, neutrófilos e células T, que geram padrões de respostas e citocinas específicos capazes de gerar mediadores que podem lesionar e inflamar o sistema vascular, resultando em oclusões venosas, arteriais e/ou formação de aneurismas.
Abstract Behçet's disease is a rare form of systemic vasculitis that affects small to large vessels. It is characterized by mucocutaneous, pulmonary, cardiovascular, gastrointestinal, and neurological manifestations. Its clinical presentation is quite wide, ranging from milder cases to severe cases, with multisystemic involvement, characteristically with exacerbations and remissions. Its etiopathogenesis is still unclear, although there is evidence of genetic, environmental, and immunological factors, such as the association with the HLA-B51 allele. In conjunction, all of these point to an abnormal immunopathological process, with activation of cells of innate and adaptive immunity, such as NK cells, neutrophils, and T cells, which generate specific response patterns and cytokines capable of generating mediators that can damage and inflame blood vessels, resulting in venous and arterial occlusions and/or aneurysm formation.
الموضوعات
Humans , Behcet Syndrome/genetics , Behcet Syndrome/immunology , HLA-B51 Antigen/immunology , Behcet Syndrome/complications , Behcet Syndrome/etiology , Behcet Syndrome/drug therapy , Cytokines/adverse effectsالملخص
Abstract The COVID-19 outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global major concern. In this review, we addressed a theoretical model on immunopathogenesis associated with severe COVID-19, based on the current literature of SARS-CoV-2 and other epidemic pathogenic coronaviruses, such as SARS and MERS. Several studies have suggested that immune dysregulation and hyperinflammatory response induced by SARS-CoV-2 are more involved in disease severity than the virus itself. Immune dysregulation due to COVID-19 is characterized by delayed and impaired interferon response, lymphocyte exhaustion and cytokine storm that ultimately lead to diffuse lung tissue damage and posterior thrombotic phenomena. Considering there is a lack of clinical evidence provided by randomized clinical trials, the knowledge about SARS- CoV-2 disease pathogenesis and immune response is a cornerstone to develop rationale-based clinical therapeutic strategies. In this narrative review, the authors aimed to describe the immunopathogenesis of severe forms of COVID-19.(AU)
الموضوعات
Humans , Pneumonia, Viral/immunology , Coronavirus Infections/immunology , Betacoronavirus/drug effects , Thrombosis/etiology , Cytokines/adverse effectsالملخص
La brucelosis es una de las enfermedades zoonóticas más importantes a nivel mundial capaz de producir enfermedad crónica en los seres humanos. La localización osteoarticular es la presentación más común de la enfermedad activa en el hombre. Sin embargo, algunos de los mecanismos moleculares implicados en la enfermedad osteoarticular han comenzado a dilucidarse recientemente. Brucella abortus induce daño óseo a través de diversos mecanismos en los cuales están implicados TNF-α y RANKL. En estos procesos participan células inflamatorias que incluyen monocitos/macrófagos, neutrófilos, linfocitos T del tipo Th17 y linfocitos B. Además, B. abortus puede afectar directamente las células osteoarticulares. La bacteria inhibe la deposición de la matriz ósea por los osteoblastos y modifica el fenotipo de estas células para producir metaloproteinasas de matriz (MMPs) y la secreción de citoquinas que contribuyen a la degradación del hueso. Por otro lado, la infección por B. abortus induce un aumento en la osteoclastogénesis, lo que aumenta la resorción de la matriz ósea orgánica y mineral y contribuye al daño óseo. Dado que la patología inducida por Brucella afecta el tejido articular, se estudió el efecto de la infección sobre los sinoviocitos. Estos estudios revelaron que, además de inducir la activación de estas células para secretar quemoquinas, citoquinas proinflamatorias y MMPs, la infección inhibe la muerte por apoptosis de los sinoviocitos. Brucella es una bacteria intracelular que se replica en el retículo endoplásmico de los macrófagos. El análisis de los sinoviocitos infectados con B. abortus indicó que las bacterias también se multiplican en el retículo endoplasmático, lo que sugiere que la bacteria podría usar este tipo celular para la multiplicación intracelular durante la localización osteoarticular de la enfermedad. Los hallazgos presentados en esta revisión intentan responder a preguntas sobre los mediadores inflamatorios implicados en el daño osteoarticular causado por Brucella. (AU)
Brucellosis is one of the most important zoonotic diseases that can produce chronic disease in humans worldwide. Osteoarticular involvement is the most common presentation of human active disease. The molecular mechanisms implicated in bone damage have started to be elucidated. B. abortus induces bone damage through diverse mechanisms in which TNF-α and RANKL are implicated. These processes are driven by inflammatory cells, including monocytes/macrophages, neutrophils, Th17 lymphocytes and B cells. Also, Brucella abortus (B. abortus) can directly affect osteoarticular cells. The bacterium inhibits bone matrix deposition by osteoblast and modifies the phenotype of these cells to produce matrix methalloproteinases (MMPs) and cytokine secretion that contribute to bone matrix degradation. B. abortus also affects osteoclast increasing mineral and organic bone matrix resorption and contributing to bone damage. Since the pathology induced by Brucella species involves joint tissue, experiments conducted in sinoviocytes revealed that besides inducing the activation of these cells to secrete chemokines, proinflammatory cytokines and MMPS, the infection also inhibits sinoviocyte apoptosis. Brucella is an intracellular bacterium that replicate in the endoplasmic reticulum of macrophages. The analysis of B. abortus infected sinoviocytes indicated that bacteria also replicate in their reticulum suggesting that the bacterium could use this cell type for intracellular replication during the osteoarticular localization of the disease. The findings presented in this review try to answer key questions about the inflammatory mediators involved in osteoarticular damage caused by Brucella. (AU)
الموضوعات
Humans , Animals , Osteoarthritis/pathology , Brucella abortus/pathogenicity , Brucellosis/pathology , Osteoarthritis/immunology , Osteoblasts/pathology , Osteocytes/microbiology , Osteogenesis/immunology , Brucella abortus/immunology , Brucellosis/etiology , Brucellosis/immunology , B-Lymphocytes/pathology , Cytokines/adverse effects , Tumor Necrosis Factor-alpha/adverse effects , Matrix Metalloproteinases/chemical synthesis , RANK Ligand/adverse effects , Th17 Cells/pathology , Synoviocytes/immunology , Macrophages/pathology , Neutrophils/pathologyالملخص
Allergic asthma is a chronic, complex inflammatory disease of the airway. Despite extensive studies on the immunomodulation of T helper (Th) cell pathways (i.e., Th1 and Th2) in asthma, little is known about the effects of Th17 pathway modulation, particularly that involving peroxisome proliferator-activated receptors (PPARs). In response, two new thiazolidinedione derivatives-namely, LPSF-GQ-147 and LPSF-CR-35 were synthesized and evaluated for their immunomodulatory effects on Th17-related cytokines, including interferon γ (IFNγ), interleukin IL-6, IL-17, and IL-22 in the peripheral blood mononuclear cells of asthmatic children. Both compounds were nontoxic even at high concentrations (i.e., 100 µM). The LPSF-CR-35 compound significantly reduced the levels of IL-17A (p = .039) and IFNγ (p = .032) at 10 µM. For IL-22 and IL-6, significant reduction occurred at 100 µM (p = .039 and p = .02, respectively). Conversely, LPSF-GQ-147 did not significantly inhibit the production of the tested cytokines, the levels of all of which were more efficiently reduced by LPSF-CR-35 than methylprednisolone, the standard compound. Real-time polymerase chain reaction assay confirmed that LPSF-GQ-147 has significant PPARγ modulatory activity. Such data indicate that both LPSF-CR-35 and LPSF-GQ-147 are promising candidates as drugs for treating inflammation and asthma
الموضوعات
Animals , Male , Rats , Asthma/complications , Child , Thiazolidinediones/analysis , Cytokines/adverse effects , Th17 Cellsالملخص
INTRODUÇÃO: O vírus linfotrópico das células T humano tipo 1 (HTLV-1) é endêmico na Bahia e está associado com doenças graves, como a Paraparesia Espástica Tropical/Mielopatia associada ao HTLV-1 (HAM/TSP) e a Dermatite Infecciosa associada ao HTLV-1 (DIH). Escassos trabalhos tem sido reportados com a avaliação de citocinas e quimiocinas em indivíduos jovens infectados pelo HTLV-1 e não existem dados sobre a manifestação simultânea DIH e HAM/TSP na faixa infanto-juvenil. OBJETIVO: Avaliar as concentrações plasmáticas de citocinas e quimiocinas na infecção pelo HTLV-1 em indivíduos infanto-juvenis. MÉTODO: Foram incluídos 61 indivíduos portadores do HTLV-1 distribuídos nos grupos Portadores assintomáticos, pacientes com a DIH, pacientes com DIH/HAM/TSP, pacientes com a HAM/TSP e 20 indivíduos saudáveis sem a infecção pelo HTLV-1, todos na faixa infanto-juvenil. As concentrações plasmáticas foram comparadas através do método de Elisa e de Cytometric Bead Array (CBA)...
INTRODUCTION: The lymphotropic virus of cells T human type 1 (HTLV ) is endemic in Bahia and it is associated with serious diseases such as Tropical Spastic Paraparesis/associated myelopathy with HTLV-1 and Infectious Dermatitis associated with HTLV -1 (IDH). Very little work has been reported with the evaluation of cytokines and chemokines in the IDH and there has been no data on the manifestation simultaneous IDH and HAM/TSP in children and youth range. OBJECTIVE: To evaluate the plasma concentrations of cytokines and chemokines in HTLV-1 infection in children and young individuals. METHOD: We included 61 individuals HTLV-1 spread in groups Asymptomatic Carriers, patients with IDH, patients with IDH/HAM/TSP, patients with HAM/TSP and 20 healthy individuals without HTLV-1, all in children's range. Plasma concentrations were compared using the ELISA method and Cytometric Bead Array (CBA)...
الموضوعات
Humans , Cytokines/analysis , Cytokines/adverse effects , Cytokines/immunology , Cytokines/blood , Cytokines/chemical synthesis , Cytokines/ultrastructure , Lymphocytes , Lymphocytes/pathology , Human T-lymphotropic virus 1/isolation & purification , Human T-lymphotropic virus 1/pathogenicityالملخص
A artrite reumatoide (AR) é uma doença inflamatória crônica, caracterizada por inflamação das articulações e se manifesta por inchaço e incapacidade funcional das mesmas. A patologia da doença envolve a produção excessiva de radicais livres pelos neutrófilos ativados, podendo induzir à peroxidação lipídica nas membranas celulares o que leva ao aumento da inflamação. Nesse sentido, o selênio (principal fonte é a castanha-do-brasil) é um importante fator por diminuir a atividade dos hidroperóxidos por meio da ação da enzima antioxidante glutationa peroxidase (GPx). No entanto, estudos que avaliem a associação do estado nutricional relativo ao selênio em pacientes com AR com os biomarcadores do estresse oxidativo e de inflamação são escassos na literatura. Desse modo, a avaliação do efeito potencial in vivo da suplementação com castanha-do-brasil, como fonte de selênio, sobre os parâmetros descritos anteriormente e sua relação com o polimorfismo Pro198Leu no gene da GPx1, em pacientes com artrite reumatoide (AR), vêm a suprir essa lacuna. Inicialmente foi realizada a caracterização da castanha-do-brasil quanto à composição de macronutrientes e teor de selênio. O estudo em pacientes com artrite reumatoide foi de natureza longitudinal. Foram avaliados 46 pacientes com AR, com idade média de 55,2 ± 10,9 anos, atendidos no Setor de Reumatologia da Universidade Federal de São Paulo. O estudo foi dividido em duas fases: antes (T0) e após a suplementação (T1) com 1 nóz de castanha-do-brasil. Foi realizada a avaliação da composição corporal e do consumo alimentar. Além disso, foram avaliados parâmetros bioquímicos relativos ao status de selênio por espectrofotometria de absorção atômica por geração de hidretos; atividades da GPx e SOD com uso de kits comerciais; concentração da GPx1 por kits comerciais, sua expressão gênica (qRT-PCR) e genotipagem do Pro198Leu no referido gene por PCR em tempo real; determinação de 8-isoprostanos por kit comercial, assim como níveis circulantes de fibrinogênio, proteína C reativa, IL-6, IL-10, TNF-α, IL-1ß, IL-2, VCAM, ICAM, PAI-1 e sE-selectina pelo ensaio ELISA. O genótipo selvagem (Pro/Pro) foi observado em 57,63% das participantes; 35,59% para as heterozigotas para o alelo variante (Pro/Leu) e 6,78% apresentaram os dois alelos variantes. As pacientes com artrite reumatoide apresentaram baixa ingestão de selênio e, após a intervenção, o consumo aumentou significantemente. Em relação ao status de selênio, houve um aumento em sua concentração no plasma e eritrócitos após o período de intervenção com castanha-do-brasil, assim como na atividade da GPx, na concentração da GPx1 e em sua expressão gênica. Níveis urinários reduzidos de 8-isoprostano e nenhuma alteração quanto à capacidade antioxidante total plasmática e quanto aos marcadores inflamatórios foram observados após o período de intervenção. Por outro lado, houve um aumento nas concentrações séricas das moléculas de adesão celulares. Portanto, pode-se concluir que a suplementação com castanha-do-brasil mostrou-se efetiva em melhorar o estado nutricional relativo ao selênio dos pacientes e os marcadores de estresse oxidativo, todavia a ingestão de 350 µgSe/dia não foi suficiente para promover uma melhora do quadro inflamatório. Além disso, a presença do polimorfismo Pro198Leu modificou as respostas dos indivíduos CT e TT em relação à suplementação, sendo inferior à dos indivíduos CC
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint inflammation, manifested by swelling and joint impairment. These pathology involves excessive free radicals production by activated neutrophils leading to lipid peroxidation in cell membranes and increased inflammation. Accordingly, selenium (Brazil-nut as main source) is an important factor reducing hydroperoxides through the improvement of glutathione peroxidase (GPx) activity. However, studies evaluating their association with oxidative stress biomarkers and inflammation in RA patients are scarce. Thus, the assessment of the in vivo potential Brazil nut supplementation on the parameters described above and its relationship to the polymorphism Pro198Leu in GPx1 gene in patients with rheumatoid arthritis, come to fill this gap. First of all, we analysed macronutrients and selenium content in Brazil nut. This is a longitudinal study with 46 RA patients attending rheumatologic treatment at Federal University of São Paulo and whose mean age were 55.2 ± 10.9 years. The present study was carried out by two phases, before and after one Brazil ingestion. We evaluated selenium status by spectrophotometry absorption with hydride generation; body composition, SOD, GPx activites, GPx1 concentration and 8- isoprostane levels, using commercial Kits; gene expression by RT-PCR and genotyping using real time PCR. Besides, inflamatory biomarkers were performed (fibrinogen, C reactive protein, IL-6, IL-10, TNF-α, IL-1ß, IL-2, VCAM, ICAM, PAI-1 e sE-selectin by ELISA. The wild genotype (Pro/Pro) was observed in 57.63% of the participants, 35.59% were heterozygote for variant allele (Pro/Leu) and 6.78% had two variant alleles. Patients with rheumatoid arthritis had low selenium intake and after the intervention, consumption of this element increased significantly. Selenium status increased significantely after Brazil nut ingestion, as well as GPx activity, GPx1concentration and its gene expression. Reduced urinary levels of 8-isoprostane and no change for total plasma antioxidant capacity and markers for inflammation were observed after the intervention period. On the other hand, there was an increase in serum concentrations of cell adhesion molecules. Therefore, it can be concluded that Brazil-nut supplementation proved to be effective in improving selenium status and markers of oxidative stress in RA patients, however ingestion of 350 µgSe/day wasn't enough to ameliorate inflammation. Besides, the presence of Pro198Leu polymorphisms interfere in supllementation response in CT and TT groups, being less responsive than CC ones
الموضوعات
Humans , Male , Female , Polymorphism, Genetic , Arthritis, Rheumatoid/pathology , Selenium/administration & dosage , Cytokines/adverse effects , Oxidative Stress , Bertholletia/metabolism , Glutathione Peroxidase/adverse effects , Inflammation/classificationالملخص
Alzheimer's disease is the preeminent cause and commonest form of dementia. It is clinically characterized by a progressive descent in the cognitive function, which commences with deterioration in memory. The exact etiology and pathophysiologic mechanism of Alzheimer's disease is still not fully understood. However it is hypothesized that, neuroinflammation plays a critical role in the pathogenesis of Alzheimer's disease. Alzheimer's disease is marked by salient inflammatory features, characterized by microglial activation and escalation in the levels of pro-inflammatory cytokines in the affected regions. Studies have suggested a probable role of systemic infection conducing to inflammatory status of the central nervous system. Periodontitis is common oral infection affiliated with gram negative, anaerobic bacteria, capable of orchestrating localized and systemic infections in the subject. Periodontitis is known to elicit a "low grade systemic inflammation" by release of pro-inflammatory cytokines into systemic circulation. This review elucidates the possible role of periodontitis in exacerbating Alzheimer's disease. Periodontitis may bear the potential to affect the onset and progression of Alzheimer's disease. Periodontitis shares the two important features of Alzheimer's disease namely oxidative damage and inflammation, which are exhibited in the brain pathology of Alzheimer's disease. Periodontitis can be treated and hence it is a modifiable risk factor for Alzheimer's disease.
A doença de Alzheimer é uma proeminente causa e a forma mais comum de demência. Caracteriza-se clinicamente por uma progressiva diminuição da função cognitiva, que tem início com a deterioração da memória. A exata etiologia e o mecanismo fisiopatológico da doença de Alzheimer ainda não são totalmente compreendidos. No entanto, postula-se que a neuroinflamação desempenhe um papel crucial na patogênese da doença de Alzheimer. A doença de Alzheimer é caracterizada por importantes características inflamatórias, assinalada pela ativação microglial e escalada dos níveis de citocinas pró-inflamatórias nas regiões afetadas. Estudos têm sugerido um provável papel de infecção sistêmica imbuída de estado inflamatório do sistema nervoso central. Periodontite é uma infecção oral comum associada a germes Gram-negativos, anaeróbios, capaz de orquestrar infecções localizadas e sistêmicas no paciente. É conhecida por suscitar um "baixo grau de inflamação sistêmica" pela liberação de citocinas pró-inflamatórias na circulação sistêmica. Esta revisão elucida o possível papel da periodontite no agravamento da doença de Alzheimer e pode ter o potencial de afetar o início e a progressão da doença de Alzheimer. Periodontite partilha as duas importantes características da doença de Alzheimer: dano oxidativo e inflamação, que estão presentes na patologia do cérebro com doença de Alzheimer. Periodontite pode ser tratada e, portanto, é um fator de risco modificável para a doença de Alzheimer.
الموضوعات
Humans , Alzheimer Disease/etiology , Periodontitis/complications , Cytokines/adverse effects , Disease Progression , Inflammation/complications , Inflammation/microbiology , Risk Factorsالملخص
Os venenos escorpiônicos são compostos, entre outras substâncias , por neurotoxinas, polipeptídios básicos de baixo peso molecular que atuam sobre canais iônicos alterando a liberação de mediadoes químicos. O veneno do escorpião Tityus serrulatus tem sido extensamente estudado e muitas de suas toxinas já foram bem caracterizadas e sequenciadas. Entre as mais importantes se encontra a TsTX-I, uma toxina que se liga ao sítio 4 do canal de sódio, que já foi bem estudada quanto a seus periféricos, embora seus efeitos centrais sejam pouco conhecidos...
Scorpion venoms are composed mainly neurotoxins that are basic peptides with low molecular weight acting on ionic channels, mainly sodium channel, changing the release of chemical mediators. Crude venom of Tityus serrulatus scorpion as well its toxins, has already been extensively studied. Many of the venom toxins were well characterized and sequenced. TsTX- I is one of the most important toxin present in the the venom. This toxin actin by binding on site 4 of sodium channel, its peripherical effects have been well studied but its central effects are not well kmow...
الموضوعات
Animals , Rats , Cytokines/adverse effects , Cytokines/toxicity , Scorpion Venoms/adverse effects , Scorpion Venoms/toxicity , Epilepsy , Hippocampus , Toxicity/adverse effectsالملخص
NF-kappaB activation has been implicated as a key signaling mechanism for pancreatic beta-cell damage. Sulfuretin is one of the main flavonoids produced by Rhus verniciflua, which is reported to inhibit the inflammatory response by suppressing the NF-kappaB pathway. Therefore, we isolated sulfuretin from Rhus verniciflua and evaluated if sulfuretin could inhibit cytokine- or streptozotocin-induced beta-cell damage. Rat insulinoma RINm5F cells and isolated rat islets were treated with IL-1beta and IFN-gamma to induce cytotoxicity. Incubation of cells and islets with sulfuretin resulted in a significant reduction of cytokine-induced NF-kappaB activation and its downstream events, iNOS expression, and nitric oxide production. The cytotoxic effects of cytokines were completely abolished when cells or islets were pretreated with sulfuretin. The protective effect of sulfuretin was further demonstrated by normal insulin secretion of cytokine-treated islets in response to glucose. Treatment of mice with streptozotocin resulted in hyperglycemia and hypoinsulinemia, which was further evidenced by immunohistochemical staining of islets. However, the diabetogenic effects of streptozotocin were completely prevented when mice were pretreated with sulfuretin. The anti-diabetogenic effects of sulfuretin were also mediated by suppression of NF-kappaB activation. Collectively, these results indicate that sulfuretin may have therapeutic value in preventing beta-cell damage.
الموضوعات
Animals , Male , Mice , Rats , Benzofurans/pharmacology , Cell Line , Cytokines/adverse effects , Diabetes Mellitus, Experimental/drug therapy , Flavonoids/pharmacology , Hypoglycemic Agents/pharmacology , Insulin-Secreting Cells/drug effects , Mice, Inbred ICR , NF-kappa B/metabolism , Rats, Sprague-Dawley , Rhus/chemistryالملخص
Introdução: o efeito antinflamatório dosglicocorticóides tem implicações clínicas que interferem de forma decisiva na evolução de pacientes submetidosa procedimentos cirúrgicos. Objetivos: realizar uma revisão sobre o uso adequado de corticosteróides emcirurgia. Métodos: Foram coletados e analisados artigos referentes ao emprego de corticoterapia em pacientescríticos, bem como pacientes submetidos a procedimentos eletivos. Todos os artigos foram extraídos do banco de dados Medline.Discussão: Apesar de seusinúmeros efeitos colaterais, é clara na literatura a participação dos corticosteróides na modulação doprocesso inflamatório sistêmico durante uma situação de estresse. A administração de tais drogas durante oprocedimento cirúrgico deriva do seu emprego prévio em pacientes em sepse e cujo prognóstico sofreuconsiderado impacto após sua indicação em maior escala. Conclusões: Concluímos que o uso de corticosteróides nas doses e intervalos definidos promove benefícios a homeostasia dos pacientes submetidos aprocedimento cirúrgicos, bem como, evolução pósoperatória com menor morbidade .
Background: the anti-inflamatory effect of the glicocorticoids have clinical implication in the evolution of patients that go under surgical procedures. Objective: Review the appropriate use of glucocorticoids in surgery.Methods: articles focused in corticotherapy in critically illpatients as well as corticotherapy in patients that go under elective procedures were selected and analyzed. All the articles were selected from Medline data base. Discussion:Despite of its large number of collateral effect, its well defined in the literature the use of corticosteroids in themodulation of the systemic inflammatory process along a situation of stress. The administration of this drugs alongthe surgical procedure comes from its usage in patients with sepsis which prognosis suffered important impact after its indication in large scale. Conclusions: we concluded that the use of corticosteroids in doses and defined period of time has benefits in the homeo stasis of patients submitted to surgical procedures as well as a less morbidityin the postoperative time .
الموضوعات
Humans , Adrenal Cortex Hormones , Anti-Inflammatory Agents , Cytokines , General Surgery , General Surgery/statistics & numerical data , Cytokines/administration & dosage , Cytokines/antagonists & inhibitors , Cytokines/adverse effects , Cytokines/pharmacology , Cytokines/metabolism , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/antagonists & inhibitors , Adrenal Cortex Hormones/adverse effectsالموضوعات
Humans , Female , Animals , Mice , Killer Cells, Natural , Endometriosis/immunology , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/therapeutic use , Flow Cytometry/trends , Cytokines/adverse effects , Endometriosis/etiology , Endometriosis/physiopathology , Infertility, Female/etiology , Pentoxifylline/therapeutic use , T-Lymphocytes, Cytotoxic , T-Lymphocytes, Helper-Inducerالموضوعات
Animals , Mice , Acute-Phase Reaction , Chagas Disease/pathology , Edema/etiology , Cytokines/adverse effects , Cytokines/pharmacology , Miceالملخص
Prurito es un síntoma frecuente y predominante en varias patologías cutáneas, sistémicas y psicosomáticas. La patogénesis del prurito ha sido clásicamente relacionada a histamina. En esta revisión, se presenta la participación de otros mediadores inmunológicos y neuroendocrinos en su fisiopatología, cuya comprensión contribuye a un mejor enfrentamiento del paciente con prurito