Astragaloside IV alleviates stroke-triggered early brain injury by modulating neuroinflammation and ferroptosis via the Nrf2/HO-1 signaling pathway

Purpose: Stroke is an acute cerebrovascular disease. Astragaloside IV (AS-IV) is an active ingredient extracted from Astragalus membranaceus with an established therapeutic effect on central nervous system diseases. This study examined the neuroprotective properties and possible mechanisms of AS-IV in stroke-triggered early brain injury (EBI) in a rat transient middle cerebral artery occlusion (MCAO) model. Methods: The neurological scores and brain water content were analyzed. 2,3,5-triphenyl tetrazolium chloride (TTC) staining was utilized to determine the infarct volume, neuroinflammatory cytokine levels, and ferroptosis-related genes and proteins, and neuronal damage and molecular mechanisms were evaluated by terminal deoxynucleotidyl transferase dutp nickend labeling (TUNEL) staining, western blotting, and real-time polymerase chain reaction. Results: AS-IV administration decreased the infarct volume, brain edema, neurological deficits, and inflammatory cytokines TNF-α, interleukin-1ß (IL-1ß), IL-6, and NF-κB, increased the levels of SLC7A11 and glutathione peroxidase 4 (GPX4), decreased lipid reactive oxygen species (ROS) levels, and prevented neuronal ferroptosis. Meanwhile, AS-IV triggered the Nrf2/HO-1 signaling pathway and alleviated ferroptosis due to the induction of stroke. Conclusion: Hence, the findings of this research illustrate that AS-IV administration can improve delayed ischemic neurological deficits and decrease neuronal death by modulating nuroinflammation and ferroptosis via the Nrf2/HO-1 signaling pathway.

Neuro-immune interactions in respiratory diseases / 生理学报

The nervous system and the immune system are relatively independent but interactional, and neuro-immune regulation is very important for the respiratory system to resist external harmful stimuli and to maintain homeostasis. Neuro-immune interaction is involved in the occurrence and development of respiratory diseases, and is essential for monitoring and modulating inflammation and tissue repair. This article summaries the neuro-immune regulation of respiratory system and discusses its role in respiratory diseases, aiming to provide a theoretical basis for further understanding the crosstalk between the nervous and immune systems, to explore the underlying mechanism in respiratory diseases, and to provide new thoughts for the prevention and treatment of respiratory diseases.

Psychoneuroimmunology and oncology nursing: a theoretical study / Psiconeuroinmunología y la enfermería oncológica: estudio teórico / Psiconeuroimunologia e a enfermagem oncológica: estudo teórico

ABSTRACT Objective: To discuss the evolution of research in cancer psychoneuroimmunology, the advances in the management of neuropsychological symptom clusters and their interface with mid-range theories, and practical applications in Nursing. Method: This is a theoretical-reflective study anchored in recent literature, as well as in the critical analysis of the authors. Results: This is a promising field of investigation, which emphasizes the complexity and interaction of symptoms, the interrelationships among them, the factors influencing them, and their consequences. Subsidized by mid-range theories in Nursing, such as the Theory of Unpleasant Symptoms and the Theory of Symptom Management, analyses of these interrelationships support Oncology Nursing diagnoses and interventions. Conclusion: An innovative approach is proposed to qualify Oncology Nursing care based on the integration of recent advances in cancer psychoneuroimmunology, Nursing mid-range theories, and practical tools such as health coaching. The approach proposed may strengthen clinical nursing practice in the management of neuropsychological symptom clusters in oncology and shall be integrated into decision-making during cancer treatment, favoring person-centered care.

RESUMEN Objetivo: Discutir la evolución de las investigaciones en psiconeuroinmunología del cáncer, los avances en el manejo de los clusters de síntomas neuropsicológicos y su interface con teorías de rango medio y aplicaciones prácticas por la Enfermería. Método: Estudio teórico-reflexivo ancorado en literatura reciente, así como en el análisis crítico de los autores. Resultados: Este es un campo promisor de investigación, que tiene énfasis en la complejidad y la interacción de los síntomas, las interrelaciones entre ellos, los factores que los influyen y sus consecuencias. Subsidiadas por teorías de rango medio en Enfermería, como la Teoría de los Síntomas Desagradables y la Teoría del Manejo de Síntomas, análisis de estas interrelaciones corroboran los diagnósticos y las intervenciones de Enfermería en Oncología. Consideraciones Finales: Se ha propuesto un abordaje innovador para calificar el cuidado de Enfermería Oncológica a partir de la integración de avances recientes en psiconeuroinmunología del cáncer, teorías de rango medio de Enfermería y herramientas prácticas como coaching de salud. El abordaje propuesto puede fortalecer la práctica clínica de Enfermería en la gestión de los clusters de síntomas neuropsicológicos en oncología y debe ser integrado en las acciones y decisiones durante el tratamiento oncológico que favorezcan el cuidado centrado en las personas.

RESUMO Objetivo: Discutir a evolução das pesquisas em psiconeuroimunologia do câncer, os avanços no manejo dos clusters de sintomas neuropsicológicos e sua interface com teorias de médio alcance e aplicações práticas pela Enfermagem. Método: Estudo teórico-reflexivo ancorado em literatura recente, bem como na análise crítica dos autores. Resultados: Este é um campo promissor de investigação, que enfatiza a complexidade e a interação dos sintomas, as inter-relações entre os mesmos, os fatores que os influenciam e suas consequências. Subsidiadas por teorias de médio alcance em Enfermagem, como a Teoria dos Sintomas Desagradáveis e a Teoria de Gerenciamento de Sintomas, análises destas inter-relações corroboram os diagnósticos e as intervenções de Enfermagem em Oncologia. Conclusão: Propõe-se uma abordagem inovadora para qualificar o cuidado de Enfermagem Oncológica a partir da integração de avanços recentes em psiconeuroimunologia do câncer, teorias de médio alcance de Enfermagem, e ferramentas práticas como coaching de saúde. A abordagem proposta pode fortalecer a prática clínica da Enfermagem no manejo dos clusters de sintomas neuropsicológicos em oncologia e deve ser integrada na tomada de decisões durante o tratamento oncológico, favorecendo o cuidado centrado na pessoa.

Cholinergic anti-inflammatory pathway and its role in treatment of sepsis / 中南大学学报(医学版)

The cholinergic anti-inflammatory pathway (CAP) is a neuro-immunomodulatory pathway,in which acetylcholine (ACh) released by the interaction of vagal nerves with α7 nicotinic acetylcholine receptor (α7nAChR),which prevents the synthesis and release of pro-inflammatory cytokines and ultimately regulates the local or systemic inflammatory response in a feedback manner. It has been shown that there are many possible effective treatments for sepsis, including vagus nerve stimulation by physical therapy, drugs such as acetylcholine receptor agonist and ultrasound therapy.

Cholinergic anti-inflammatory pathway plays negative regulatory role in early inflammatory and immune responses in septic rats / 南方医科大学学报

OBJECTIVE@#To investigate the role of cholinergic anti-inflammatory pathway (CAP) in neuro-regulation of inflammatory and immune response in the early stage of sepsis.@*METHODS@#Sixty-four SD rats were randomly divided into control Group (=8) with normal feeding without any treatment; sham operation group (=8) with laparotomy but without cecal ligation and puncture (CLP), followed by intraperitoneal injection 50 mg/kg piperacillin 3 times a day for 3 consecutive days; and sepsis group (=48) with CLP-induced sepsis. The rat models of sepsis were randomized into model groups (=16) with intraperitoneal injection of piperacillin (50 mg/kg) and normal saline (1 mL/100 g) for 3 times a day for 3 days; GTS-21 group (=16) with additional intraperitoneal injection of 4 mg/kg GTS-21 (once a day for 3 days); and methyllycaconitine (MLA) group (=16) with intraperitoneal injection of MLA (4.8 mg/kg) in addition to piperacillin (once a day for 3 days). Murine Sepsis Score (MSS) of the rats and short-range HRV analysis were recorded. Three days later, the rats were sacrificed and serum levels of TNF-α, IL-1α, IL-10, IL-6, HMGB1, and sCD14 were measured with ELISA. The percentages of CD4CD25 Treg and TH17 lymphocytes and their ratios were measured using flow cytometry.@*RESULTS@#Compared with the control rats, the septic rats had significantly increased MSS scores and lowered HRV indexes (SDNN, RMSSD, HF, SD1, and SD2; < 0.05); treatment with GTS-21 significantly decreased while MLA increased MSS scores ( < 0.05), but neither of them obviously affected HRV of the rats. Serum levels TNF-α, IL-1α, IL-10, IL-6, HMGB1, and sCD14 and the percentages of CD4CD25 Treg and TH17-positive lymphocytes were significantly higher and Treg/TH17 ratio was significantly lower in the septic rats compared with those in the control group ( < 0.05); treatment with GTS-21 significantly decreased the levels of serum levels of TNF-α, IL-1α, IL-6, HMGB1, and sCD14 and TH17 lymphocyte percentage ( < 0.05), whereas MLA treatment significantly increased serum levels of TNF-α, IL-1α, IL-10, IL-6, HMGB1, and sCD14 and the percentages of CD4 CD25 Treg and TH17-positive lymphocytes and decreased Treg/TH17 ratio in the septic rats ( < 0.05).@*CONCLUSIONS@#CAP plays negative regulatory role in early inflammatory and immune response to sepsis, and some of the HRV indicators can well reflect the regulatory effect of CAP on inflammation and immunity in the septic rats.

What does immunology have to do with brain development and neuropsychiatric disorders?

Introduction: Neural development is an enormously complex and dynamic process. From very early in brain development 'immune cells' play a key role in a number of processes including the formation and refinement of neural circuits, as well as sexual differentiation. There is a growing body of evidence that the immune system also plays an important role in the pathobiology of several neurodevelopmental and neuropsychiatric disorders. Objective: The goal of this article is to review the currently available data concerning the role of the 'immune system' in normal brain development, as well as its role in the pathobiology of neurodevelopmental and neuropsychiatric disorders. Methodology: We conducted a traditional literature search using PubMed and recent special issues of journals to locate relevant review articles. Results: The cellular and molecular processes that make up our 'immune system' are crucial to normal brain development and the formation and maintenance of neural circuits. It is also increasingly evident that the immune system and neuroinflammation play important roles in the pathobiology of at least a subset of individuals with Autism Spectrum Disorder (ASD), schizophrenia, obsessive-compulsive disorder, Tourette syndrome and mood disorders, such as depression, as well as autoimmune and neurodegenerative disorders. Emerging evidence also points to the importance of the 'gut-brain axis' and an individual's microbiome, which can impact an individual's somatic and mental well-being. Conclusions: There are multidirectional interconnections across multiple biological systems in our brains and bodies that are mediated in part by the immune system. At present, however, the 'promise' of this field remains greater than the 'deliverables'. Time will tell whether novel interventions will be developed that will make a positive difference in the care of our patients. It is also possible that valid biomarkers will emerge that will guide a more personalized approach to treatment.

Introdução: O desenvolvimento neural é um processo extremamente complexo e dinâmico. Tao pronto se inicia o desenvolvimento do cérebro, as "células imunológicas" desempenham um papel fundamental em vários processos, incluindo a formação e aperfeiçoamento de circuitos neurais, bem como a diferenciação sexual. Há um crescente corpo de evidências de que o sistema imunológico também desempenha um papel importante na fisiopatologia de diversos transtornos neurodesenvolvimentais e neuropsiquiátricos. Objetivo: O objetivo deste artigo é revisar os dados atualmente disponíveis sobre o papel do "sistema imunológico" em relação ao desenvolvimento normal do cérebro, bem como a fisiopatogenia dos transtornos de neurodesenvolvimento e neuropsiquiátricos. Metodologia: Foi realizada uma pesquisa bibliográfica tradicional para localizar artigos de revisão relevantes. Resultados: Os processos celulares e moleculares que compõem o nosso "sistema imunológico" são cruciais para o desenvolvimento normal do cérebro e a formação e manutenção de circuitos neurais. É cada vez mais evidente que o sistema imunológico e neuroinflamação desempenham papéis importantes na etiopatogenia de pelo menos um subconjunto de indivíduos com autismo, esquizofrenia, transtorno obsessivo-compulsivo, síndrome de Tourette, depressão e transtornos do humor, bem como distúrbios autoimunes e neurodegenerativos. Evidências emergentes também apontam para a importância do eixo intestino-cerebral e do microbioma de um indivíduo em relação à sua saúde e bem-estar somático e mental. Conclusões: Existem interconexões multidirecionais entre múltiplos sistemas biológicos em nossos cérebros e corpos que são mediados em parte pelo sistema imunológico. No momento, no entanto, a "promessa" desse campo continua sendo maior do que os "resultados finais". O tempo dirá se novas intervenções serão desenvolvidas que farão uma diferença positiva no cuidado de nossos pacientes. Também é possível que surjam biomarcadores válidos que orientarão uma abordagem mais personalizada ao tratamento.

Anxiolytic properties of compounds that counteract oxidative stress, neuroinflammation, and glutamatergic dysfunction: a review

Objective: Anxiety disorders are highly prevalent and the efficacy of the available anxiolytic drugs is less than desired. Adverse effects also compromise patient quality of life and adherence to treatment. Accumulating evidence shows that the pathophysiology of anxiety and related disorders is multifactorial, involving oxidative stress, neuroinflammation, and glutamatergic dysfunction. The aim of this review was to evaluate data from animal studies and clinical trials showing the anxiolytic effects of agents whose mechanisms of action target these multiple domains. Methods: The PubMed database was searched for multitarget agents that had been evaluated in animal models of anxiety, as well as randomized double-blind placebo-controlled clinical trials of anxiety and/or anxiety related disorders. Results: The main multitarget agents that have shown consistent anxiolytic effects in various animal models of anxiety, as well in clinical trials, are agomelatine, N-acetylcysteine (NAC), and omega-3 fatty acids. Data from clinical trials are preliminary at best, but reveal good safety profiles and tolerance to adverse effects. Conclusion: Agomelatine, NAC and omega-3 fatty acids show beneficial effects in clinical conditions where mainstream treatments are ineffective. These three multitarget agents are considered promising candidates for innovative, effective, and better-tolerated anxiolytics.

Antibody Index in neuroimmunoepidemiological studies

The evaluation of the neuroimmunoepidemiological response from the reibergram allows the determination of the specific antibody index for a determined etiological agent. This evaluation has served to know the behavior of the neuroimmune response in pediatric patients to different herpesviruses, evaluate the effectiveness of vaccination campaigns and find a response that helps in the diagnosis of various processes that affect this system(AU)

Human neuroimmune response against angiostrongylus cantonensis

Introduction: Angiostrongylus cantonensis is a zoonotic pathogen that causes human angiostrongyliasis; its main clinical manifestation is eosinophilic meningitis. It was reported in Cuba for the first time in America. Objective: To review the main immunological findings about the human neuroimmune response against this parasite. Methods: This paper is based on a review of the papers mainly from Cuban authors published in the last 10 years about the human neuroimmune response against this helmint. This information becomes more relevant after the introduction of the African giant snail Lissachatina fulica in Cuba in 2014. Results: The humoral immune response is based on the immunoglobulin intrathecal synthesis. When the third-stage larvae go to the central nervous system at the first lumbar puncture there are no major immunoglobulin synthesis. One week later an immune intrathecal response is done by a two-class major immunoglobulin class mainly IgG+ IgA Intrathecal activation of complement is evident of intrathecal synthesis of major immunoglobulins during this disease. The activation of complement system components in cerebrospinal fluid is relevant to the understanding of this tropical disease, which is emerging in the Western hemisphere. Intrathecal synthesis of at least one of the major immunoglobulins and a wide spectrum of patterns may be observed. Although intrathecal synthesis of C3c and IgE is always present, C4 intrathecal synthesis does not occur in every patient. The diversity of intrathecal synthesis and activation of the different complement pathways enables their division into three variant groups. In each one could be finding the activation of one or several complement pathways including the participation of MBL, MASP-2 and ficolins as part of the lectin pathway complement activation. Conclusion: The neuroimmune response against Angiostrongylus cantonensis eosinophilic meningoencephalitis is an example of the host-parasite interaction(AU)

A neuroimunomodulação na síndrome metabólica: a participação dos receptores do tipo Toll 4 / Neuroimmunomodulation in metabolic syndrome: the participation of Toll 4 receptors

A síndrome metabólica (SM) é definida como um estado pró-inflamatório de baixo grau, no qual fatores metabólicos e cardiovasculares anormais aumentam o risco de desenvolver doença cardiovascular e neuroinflamação. Eventos como o acúmulo de tecido adiposo visceral, aumento das concentrações plasmáticas de ácidos graxos livres, hipóxia tecidual e hiperatividade simpática na SM, podem contribuir para a ativação direta ou indireta dos receptores do tipo Toll (TLR), especificamente o TLR-4, considerado como um receptor envolvido em todos os componentes desta síndrome. A ativação da resposta imune inata, via TLR4 pode contribuir para este estado de inflamação crônica e pode estar relacionada com a neuroinflamação e neurodegeneração observadas na SM. Neste estudo, investigamos o papel dos receptores TLR4 na microcirculação cerebral e no desempenho cognitivo de camundongos com SM induzida por dieta hiperlipídica (HFD). O modelo de SM induzido por HFD em camundongos acarreta em alterações metabólicas, hemodinâmicas e microcirculatórias evidenciadas pela rarefação capilar, aumento do rolamento e adesão de leucócitos em vênulas pós-capilares e disfunção endotelial, que estão diretamente relacionadas ao declínio cognitivo e neuroinflamação

O mesmo modelo de SM reproduzido em camundongos que possuem uma mutação genética, que os torna deficientes para o TLR4, não gera tais alterações. Também demonstramos que a substituição da dieta hiperlipídica pela dieta normolipídica é capaz de reverter as alterações inflamatórias na microcirculação cerebral e este efeito, possivelmente, está relacionado a menor ativação do TLR4. Ainda verificamos que a ingestão de HFD por uma semana não é capaz de induzir alterações microcirculatórias e inflamatórias cerebrais nos animais controles e mutantes para o TLR4-HFD. Portanto, nossos resultados demonstram que o TLR4 está envolvido na disfunção microvascular e neuroinflamação associada à SM induzida por HFD e, possivelmente, desempenham um papel causal no desenvolvimento do declínio cognitivo. (AU)

Characteristics of the traditional Liu-Wei-Di-Huang prescription reassessed in modern pharmacology / 中国天然药物

Liu-Wei-Di-Huang (LW) is a Yin nourishing and kidney tonifying prescription in traditional Chinese medicine with promising pharmacological characteristics that can be further exploited and developed in modern medicine. We provide a comprehensive and detailed literature report on the clinical and experimental pharmacology of LW, including its quality control parameters, phytochemistry, pharmacokinetics, and toxicology. Our literature review indicates that the LW prescription possesses a unique combination of pharmacological characteristics that can be safely used for treating very different diseases. Quality control and pharmacokinetic parameters of LW are mostly based on its major bioactive phytochemical constituents. We postulate that modulating or rebalancing the neuroendocrine immunomodulation network in the body is the underlying mechanism of the multiple pharmacological activities displayed by LW.

Estrés, psiconeuroendocrinoinmunología y enfermedades reumatológicas. Actualización del tema / Stress, Psychoneuroendocrinoimmunology and rheumatological diseases. Actualization of this topic

El estrés se define como el estado de alarma de los organismos ante diversos desafíos. La Psiconeuroendocrinoinmunología es una ciencia que integra la psiquis, el sistema nervioso, endocrino e inmune; y estudia las múltiples y complejas interrelaciones entre ellos lo cual permite tratar de manera integral el proceso salud-enfermedad. La alteración del equilibrio entre la psiquis y los sistemas mencionados puede ocasionar daños al organismo como es el caso de algunas enfermedades reumatológicas(AU)

Stress is defined as the state of alarm of living beings in case of various challenges. Psycho-neuro-endocrine-immunology is a science that integrates the psyche with the nervous, endocrine and immune systems. It studies the multiple and complex interrelations among them, which allows us to deal comprehensively with the health-disease process. The alteration if the balance between the psyche and the aforementioned systems can cause damage to the organism, as in the case of some rheumatologic diseases(AU)

Gluten and Neuroimmunology. Rare association with Myasthenia Gravis and Literature Review

SUMMARY As the celiac disease (CD), the non-celiac gluten sensitivity (NCGS) has also been associated with several autoimmune manifestations. It is rarely associated with myasthenia gravis (MG). This paper shall introduce the case of a young female patient, initially presenting a peripheral neuropathy framework. During clinical and neurological follow-up, she began to present symptoms of various immune-mediated morbidities. Diseases related to gluten represent a clinical spectrum of manifestations with a trigger in common, the ingestion of gluten. CD is the most well-known and serious disease of the spectrum, also called gluten-sensitive enteropathy. The NCGS is diagnosed from clinical evidence of improvement in symptoms followed by a Gluten Free Diet (GFD) in patients without signs of enteropathy in duodenal biopsy. There are indications that, although rare, with a prevalence of 1 in 5000, myasthenia gravis (MG) may occur more often when CD is also present. Between 13 to 22% of the patients with MG have a second autoimmune disorder. However, it is often associated with dermatomyositis or polymyositis, lupus erythematosussystemic lupus erythematosus, Addison's disease, Guillain-Barré syndrome and juvenile rheumatoid arthritis. Thus, the symptoms of neuromuscular junction involvement may give a diagnostic evidence of this rare association.

Etiopatogenia de la hemorragia digestiva alta no variceal, respuesta inflamatoria y Helicobacterpylori / Etiopathogeny of the non-variceal high digestive hemorrhage, inflammatory answer and Helicobacter pylori

RESUMEN La infección por la bacteria Helicobacter pylori ocurre a nivel mundial, aunque es más frecuente en países en vías de desarrollo y en comunidades en condiciones socioeconómicas pobres, donde existe hacinamiento o migración de regiones de prevalencia alta. La infección ocurre principalmente durante la infancia y se incrementa con la edad. Se realizó una revisión exhaustiva donde se explican de manera explícita los mecanismos que desencadenan la respuesta inflamatoria una vez que la bacteria coloniza el estómago, que incluye dos etapas: la primera caracterizada por la llegada y penetración del microorganismo al moco gástrico, donde se asienta y se multiplica y la segunda etapa caracterizada por una amplificación de esta respuesta inflamatoria. El conocimiento de estos mecanismos etiopatogénicos no sólo ayuda a la erradicación de la bacteria, sino que contribuye a la regulación del sistema neuroinmune antes, durante y después del daño tisular, para lograr una regeneración tisular adecuada, mejorar la capacidad funcional del órgano sangrante e impedir la evolución tórpida de la enfermedad (AU).

ABSTRACT The infection by Helicobacter pylori occurs worldwide, although it is more frequent in developing countries and in communities with poor socioeconomic conditions, where there is overcrowding or migration from regions of high prevalence. The infection occurs mainly during the childhood and increases with age. An exhaustive review was carried out where the mechanisms unchaining the inflammatory answer after the bacteria colonizes the stomach are explained in an explicit way. It has two stages: the first one is characterized by the microorganism arrival and penetration to the gastric mucus, where it settles and multiplies, and the second stage characterized by an amplification of the inflammatory answer. The knowledge of these etiopathogenic mechanisms does not only help the eradication of the bacteria but also contributes to the regulation of the neuroimmune system before, during and after tissue damage, for reaching an adequate tissue regeneration, improving the functional capacity of the bleeding organ, and preventing the disease torpid evolution (AU).

Atopic dermatitis: allergic dermatitis or neuroimmune dermatitis?

Abstract: Advances in knowledge of neurocellulars relations have provided new directions in the understanding and treatment of numerous conditions, including atopic dermatitis. It is known that emotional, physical, chemical or biological stimuli can generate more accentuated responses in atopic patients than in non-atopic individuals; however, the complex network of control covered by these influences, especially by neuropeptides and neurotrophins, and their genetic relations, still keep secrets to be revealed. Itching and airway hyperresponsiveness, the main aspects of atopy, are associated with disruption of the neurosensory network activity. Increased epidermal innervation and production of neurotrophins, neuropeptides, cytokines and proteases, in addition to their relations with the sensory receptors in an epidermis with poor lipid mantle, are the aspects currently covered for understanding atopic dermatitis.

La teoría de la neuroinmunomodulación en enfermedades neurodegenerativas: nuevas evidencias científicas / Neuroinmmunomodulation in neurodegenerative diseases: new scientific evidence

Microglial cells play a major role in the innate immunity of the central nervous system. Alterations in the normal cross-talks between microglia and brain neuronal cells may lead to serious disturbances and neurodegenerative diseases. We have postulated that neuroinflammatory processes are a critical factor triggering the pathological cascade leading to neuronal degeneration. In our neuroimmunomodulation theory, external or internal damage signals activate microglial cells, producing cytotoxic factors that induce neuronal degeneration. These factors activate protein-kinases, that lead to tau hyperphosphorylation, and its consequent oligomerization. The tau aggregates released into the extracellular medium favor a positive feedback mechanism that determines neurodegeneration. Nowadays, natural components with a string anti-inflammatory activity and that cross the blood brain barrier appears as candidates for prevention and treatment of degenerative brain disorders such as Alzheimers'disease.

Las células microgliales juegan un papel importante en la inmunidad innata del sistema nervioso central. Las alteraciones en la normal diafonía celular, entre microglias y células neuronales cerebrales, pueden conducir a graves disturbios y enfermedades neurodegenerativas. En este contexto, hemos postulado que los procesos neuroinflamatorios son un factor crítico a desencadenar la cascada patológica que conduce a la degeneración neuronal. En nuestra teoría Neuroinmunomoduladora, señales de daños externos o internos activan las células microgliales, favoreciendo la producción de factores citotóxicos que inducen la degeneración neuronal. Estos factores activan la proteína-quinasas, que conducen a la hiperfosforilación de la proteína tau, y su consecuente oligomerización. Estos agregados de tau liberados al medio extracelular, al activar a la célula microglial, provocarían un mecanismo de retroalimentación positiva favoreciendo la neurodegeneración. Hoy en día, compuestos de origen natural con una fuerte actividad anti-inflamatoria, capaces de cruzar la barrera hematoencefálica del cerebro, aparecen como candidatos para la prevención y el tratamiento de trastornos neurodegenerativos tales como la enfermedad de Alzheimer.

Interações imunoendócrinas na migração de linfócitos na doença de chagas humana crônica: relação com a cardiopatia / immunendocrine interactions on lymphocyte migration in chronic human chagas disease: relationship to cardiopathy

A doença de Chagas permanece sendo um grave problema de saúde pública nas Américas. Na fisiopatologia da doença, é observada uma intensa resposta imune, com alta produção de citocinas inflamatórias e quimiocinas que contribuem para o tráfego de células ativadas para tecidos alvo. Este evento de migração celular pode estar relacionado à formação de cardiopatia chagásica nos indivíduos infectados. Um desequilíbrio na produção hormonal do eixo Hipotálamo-Pituitária-Adrenal (HPA) foi observado em pacientes chagásicos, e, esse processo pode influenciar o sistema imune e possivelmente a gênese da cardiopatia. Nesse estudo, foi avaliada a resposta migratória de células T de pacientes chagásicos com diferentes formas de cardiopatia, correlacionando esses eventos com a produção de cortisol e DHEA ocorrida na fase crônica da doença. Primeiramente foi observado que TNF, IL-6, IFN-gama, IL-17, IL-10 e TGF-beta são mais expressas de acordo com a gravidade da cardiopatia. Em paralelo a esse aumento de citocinas foi observado um desequilíbrio hormonal no eixo HPA com diminuição do hormônio DHEA sérico e aumento da razão Cortisol/DHEA circulantes. Além disso, foi observado um aumento da resposta migratória de células T, com fenótipo ativado (HLADR+/VLA-4+) sobre fibronectina, CXCL12 e TNF-alfa, e também combinados a um pré tratamento de DHEA e Cortisol destas células. Estes resultados indicam que distúrbios neuroendócrinos, correlacionados a um perfil inflamatório sistêmico, podem contribuir para aumentar o potencial migratório de células T aos sítios inflamatórios, incluindo tecido cardíaco, estando envolvidos na cardiopatia relatada na doença...

Chagas disease remains a serious public health problem in the Americas. In thepathophysiology of disease, it is observed an intense immune response with highexpression of inflammatory cytokines and chemokines that contribute to activated Tcells traffic, that target the inflamed tissue. These cell migration events may berelated to the formation of Chagas heart disease in infected individuals. Animbalance in hormone production of the Hypothalamus-Pituitary-Adrenal axis (HPA)was observed in patients with Chagas disease, and this process could influence theimmune system, including, cardiopathy formation. In this study, T cells migratoryresponse from chagasic patients with different forms of cardiopathy was performed tocorrelate these events with cortisol and DHEA production in the chronic phase of thedisease. Firstly, it was observed that inflammatory cytokines, such as TNF, IL-6, IFN-gama, IL-17, IL-10 e TGF-beta were expressed in terms of disease severity. In parallel withcytokine enhancement, it was observed a hormonal imbalance in the HPA axis,where a decrease in hormone DHEA resulted in increased cortisol ratio / circulatingDHEA. In addition, there was an increase in migratory response of T cells with anactivated phenotype (HLADR+/VLA-4+) over fibronectin, CXCL12 and TNF-alpha, andalso a combined pre treatment of DHEA and cortisol. These results indicate thatneuroendocrine disorders correlated to a systemic inflammatory profile, can increasemigration potential of T cells to inflammatory sites, including heart tissue and thusbeing involved in heart disease...

Características definidoras da Resposta Disfuncional ao Desmame Ventilatório como indicadores de acurácia do desmame ventilatório / Defining characteristics of the Dysfunctional Ventilatory Weaning Response as indicators of accuracy of ventilatory weaning / Características definitorias de la Respuesta Disfuncional al Destete Ventilatorio como indicadores de precisión del destete ventilatorio

Objetivou-se avaliar as características definidoras do diagnóstico Resposta Disfuncional do Desmame Ventilatório, como indicadores de acurácia das tentativas de desmame. Estudo observacional de 38 eventos de tentativa de desmame ventilatório em pacientes adultos internados em terapia intensiva. Para as características definidoras foram calculadas: sensibilidade, especificidade, valores preditivos positivos e negativos, acurácia ou sensibilidade, razão de verossimilhança e razão de chances diagnóstica. Também foram consideradas as medianas do número de características definidoras nos eventos de sucesso e insucesso. Foram consideradas acuradas: agitação, deterioração nos gases sanguíneos arteriais em relação aos parâmetros basais, uso moderado da musculatura acessória da respiração, aumento da frequência respiratória em relação aos parâmetros basais e frequência respiratória aumentada de forma significativa em relação aos parâmetros basais. Houve diferença estatística nas medianas do número de características definidoras observadas. Conclui-se que a característica definidora e o número delas influenciariam o sucesso da decisão sobre o desmame.

The study aimed to analyze the defining characteristics of the Dysfunctional Ventilatory Weaning Response as an indicator of the accuracy of ventilatory weaning. Observational study of 38 events of ventilatory weaning in adult patients admitted to intensive care. For the defining characteristics, it was calculated: sensitivity, specificity, positive and negative predictive values, accuracy or efficiency, likelihood ratio positive and negative, and diagnostic odds ratio. It was also considered the median number of defining characteristics in the event of success and failure. It was considered accurate: agitation, deterioration in arterial blood gases from baseline parameters, moderate use of accessory muscles of respiration, increased respiratory rate from baseline parameters and respiratory rate increases significantly with respect to baseline parameters. There was statistical difference in the median number of defining characteristics observed. It was concluded that the defining characteristic and the number of them would influence the success of the weaning decision.

El estudio tuvo como objetivo evaluar las características que definen el diagnóstico de Respuesta Disfuncional al Destete Ventilatorio como indicador de la exactitud del destete ventilatorio. Estudio observacional de 38 eventos de destete ventilatorio en pacientes adultos ingresados en cuidados intensivos. Para las características definitorias se calcularon: sensibilidad, especificidad, valores predictivos positivos y negativos, precisión o sensibilidad, cocientes de probabilidad y odds ratio diagnóstica. Fueran consideradas las medianas del número de características definitorias en casos de éxito o de fracaso. Se consideraron precisas: agitación, deterioro de los parámetros de gases en sangre arterial desde la línea de base, uso moderado de los músculos accesorios de la respiración, aumento de la frecuencia respiratoria a partir de parámetros de línea de base y frecuencia respiratoria aumentada significativamente en comparación con los parámetros de línea de base. Hubo diferencia estadísticamente significativa en la mediana del número de características definitorias observadas. Se concluye que la característica definitoria y el número de ellas influyen en el éxito de la decisión sobre el destete ventilatorio.

Perfil sérico de melatonina, citocinas e cortisol em gestantes com pré-eclâmpsia / Serum profile of melatonin, cytokines and cortisol in pregnant women with preeclampsia

A pré-eclâmpsia (PE) é a maior causa de mortalidade e morbidade materna e perinatal. Sua etiologia permanece desconhecida, o que torna impossível a realização de prevenção primária dessa doença. O entendimento do perfil de substâncias que estão alteradas na PE é de relevância para poder atuar preventivamente. Considerando que vários hormônios envolvidos na resposta imunológica participam da fisiopatologia da PE e que, como demonstrado recentemente, a melatonina tem papel relevante na fisiopatologia da inflamação aguda, nossa hipótese seria que este hormônio poderia também atuar fisiopatologia da PE. OBJETIVOS: avaliar o perfil de citocinas e hormônios no soro de pacientes com PE para estabelecer se o eixo imune-pineal estaria ativado nesta doença. MÉTODOS: Realizamos estudo prospectivo caso-controle, no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, no período de Outubro de 2010 a Outubro de 2013. O grupo experimental foi formado por pacientes com PE pura no momento do diagnóstico (sem medicação anti-hipertensiva inicial por 24h). Gestantes saudáveis e normotensas, pareadas por idade materna, idade gestacional e paridade, foram selecionadas como controles. Citocinas (TNF, IL-8, IL-6, IL-1beta, IL-4, IFN-y , VEGF , IL-10, IL-12p40, IL-17 e IL-2), cortisol, níveis séricos de melatonina pela manhã (08h-11h) e à noite (23h- 01h), assim como os níveis de 6-sulfatoximelatonina (6-SMT) nos diferentes períodos do dia (bl1:12h-18h, bl2:18h-24h,bl3:24h-06h,bl4:06-12h) foram avaliados por MULTIPLEX e ELISA. A diferença entre os grupos foi avaliada por Two-way ANOVA seguido de pós teste de Bonferroni. Foi considerada significativamente diferente quando a probabilidade da hipótese nula foi rejeitada (p < 0,05). A correlação entre parâmetros foi avaliada por regressão linear simples e teste de Pearson. RESULTADOS: De um total de 31 pacientes inicialmente avaliadas, 14 gestantes com PE e 12 controles foram incluídas. As características das...

Preeclampsia (PE) is a major cause of maternal and perinatal mortality and morbidity. Since its etiology remains unknown, it is impossible to have a primary prevention of the disease. The understanding of the substance profiles that are altered in PE is important to prevent the disease. Considering that many hormones involved in immune response are involved in the physiopathology of PE and that melatonin has a relevant role in the acute inflammatory process, our hypothesis is that this hormone would also be involved in the physiopathology of PE. OBJECTIVES: To analyze the serum profile of cytokines and hormones in pregnant women with PE in order to evaluate if the immune-pineal axis is activated in this disease. METHODS: A prospective case-control study was conducted at the Clinical Hospital USP between October 2010 and October 2013. Only patients with pure PE at the moment of diagnosis (without anti-hypertensive medication for the initial 24h after diagnosis) were included. Normotensive healthy pregnant women that were matched by maternal age, gestational age and parity were included as controls. Cytokines (IL-6, IL-1b, IL-8, TNF and IFNy), cortisol and serum melatonin levels in the morning (08h-11h) and at night (23h-01h), as well as 6-sulfatoximelatonin (6-SMT) levels in different periods of the day (bl1:12h- 18h, bl2:18h-24h, bl3:24h-06h, bl4:06-12h) were measured by MULTIPLEX and ELISA. Differences between groups were analyzed using two-way ANOVA followed by Bonferronis's test. Statistical difference was considered when the null hypothesis was rejected (p < 0.05). Correlations between parameters were analyzed using linear regression and Pearson test. RESULTS: From a total of 31 patients initially evaluated, 14 patients with PE and 12 controls were included. Demographics such as maternal age, parity, gestational age at the dosages, body-mass index were similar in both groups (p > 0.05). TNF and IL-8 levels were higher in the...