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.

¿Nos enferman las preocupaciones? Una respuesta desde la Psiconeuroinmunoendocrinología / Do we get worried sick? An answer from the Psiconeuroinmunoendocrinology

La Psiconeuroinmunoendocrinología estudia la interacción entre los procesos psíquicos y los sistemas nervioso, endocrino e inmune y, de forma integradora, las interrelaciones del proceso salud-enfermedad. Diversas investigaciones muestran la estrecha relación entre el surgimiento y desarrollo de enfermedades somáticas con determinadas alteraciones psicológicas, entre ellas el estrés, la ansiedad y depresión. El objetivo de este trabajo es sistematizar los elementos teóricos que sustentan la interrelación entre la psiquis, el sistema nervioso, endocrino e inmune en el proceso salud - enfermedad y exponer las evidencias clínicas que sustentan su validez.

The Psychoneuroimmunoendocrinology studies the interaction between psychic processes and the Nervous, Endocrine and Immune systems and, in an integrative way, the health-disease process interrelationships. Several researches show the close relation between the somatic diseases emergence and development with certain psychological alterations, among them stress, anxiety and depression. This work is aimed at systematizing the theoretical elements which demonstrate the interrelation between the psyche, the Nervous System, Endocrine and Immune System in the health - illness process and to present the clinical evidences which support its validity.

Anti-NMDA (a-NMDAR) receptor encephalitis related to acute consumption of metamphetamine: Relevance of differential diagnosis. / Encefalitis antirreceptores (a-NMDAR) en un paciente con ingesta aguda de metanfetanima: importancia del diagnóstico diferencial.

A 19-year-old male came to the Emergency Room of our hospital due to an episode of dystonic movements and disorientation 4 days after consuming methamphetamine, which evolved to a catatonic frank syndrome and eventually to status epilepticus. Definitive diagnosis was anti-NMDA receptor encephalitis, an acute inflammation of the limbic area of autoimmune origin in which early diagnosis and treatment are key elements for the final outcome. In this case, initial normal tests and previous methamphetamine poisoning delayed diagnosis, because inhaled-methamphetamine poisoning causes similar clinical symptoms to anti-NMDA receptor encephalitis. Methamphetamine poisoning may have caused an immune response in the patient, bringing on the progress of the pathology.

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.

Vías de neuroinmunomodulación. Primera parte

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Summary: Inflammation is a normal response caused by physical stress like infection, injury and trauma; and processive or psychological stress like in psychiatric diseases such as major depression, schizophrenia and posttraumatic stress. The host responds with a complex series of immune, endocrine and nervous reactions to face the stressful stimuli named neuroendocrine immune interaction. These interactions help us to maintain the homeostasis under stressful stimuli. Stress is a physicochemical or emotional process that induces tension. This process promotes the release of proinflammatory cytokines, hormones such as the corticotrophin-release hormone (CRH) and cortisol, and a wide number of neurotransmitters that are together responsible for some behavioral alterations. Both systemic and psychological stress elicits an equivalent response in an organism. Particularly, the onset of inflammation is characterized by release of pro-inflammatory mediators including tumor necrosis factor (TNF)-α, interleukin (IL)-1, adhesion molecules, vasoactive mediators, and reactive oxygen species. The early release of pro-inflammatory cytokines by a widely variety of immune and no-immune cells has a pivotal role in triggering the local inflammatory response. Apart from their involvement in local inflammation, TNF-α and IL-1β are signal molecules for activation of brain derived neuroendocrine and immunomodulatory responses. Excessive production of cytokines, such as TNF-α and IL-1β however can be more injurious than the inciting event, initiating diffuse coagulation, tissue injury, hypotension, and death. The inflammatory response is balanced by anti-inflammatory molecules like the cytokines IL-10 and IL-4, soluble TNF receptors, IL-1 receptor antagonists, and transforming growth factor (TGF)-β. Neuroendocrine pathways, such as the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic division of the Autonomic Nervous System (SNS) control the inflammation process by triggering anti-inflammatory balancing mechanisms. The brain can monitor immune status and sense peripheral inflammation through two main pathways: neural and humoral. The neural mechanism relies upon activation of vagus nerve afferent sensory fibers that signal the brain that inflammation is occurring. Stressful stimuli activate vagal afferents either directly by cytokines released from dendritic cells, macrophages, and other vagal-associated immune cells, or indirectly through the chemoreceptive cells located in vagal paraganglia. The transmission of cytokine signals to the brain through the vagal sensory neurons depends upon the magnitude of the stressful challenge. Subdiaphragmatic vagotomy inhibits the stimulation of the HPA axis and noradrenaline (NA) release in hypothalamic nuclei in response to intraperitoneal administration of endotoxin or IL-1β. Intravenous endotoxin administration induces expression of the neural activation marker c-Fos in the brainstem medulla, regardless of the integrity of the vagus nerve. Vagotomy fails to suppress high dose endotoxininduced. IL-1β immunoreactivity in the brain and increases blood corticosterone levels. It is likely that the vagal afferent neural pathway plays a dominant role in mild to moderate peripheral inflammatory responses, whereas acute, robust inflammatory responses signal the brain primarily via humoral mechanisms. By other hand, humoral pathway are supported by a large body of evidence, especially in cases of systemic immune challenge; circulatory cytokines like IL-1 β and TNF-α can cross the blood-brain barrier and enter cerebrospinal fluid and the interstitial fluid spaces of the brain and spinal cord by a saturable carrier mediated mechanism that may function only at very high plasma cytokine concentrations. Cytokines also can bind to receptors at the surface of the endothelium of the brain capillaries and can enhance the synthesis and release of soluble mediators such as prostaglandins and nitric oxide, which diffuse into the brain parenchyma and modulate the activity of specific groups of neurons. It has been suggested that prostaglandins mediate fever and HPA axis activation. Cytokine-to-brain communication also may occur via circumventricular organs that lack normal blood-brain barrier function. Among the circumventricular organs, the AP (area postrema) appears to represent the best candidate for such a transduction site. The AP is located in the floor of the caudal fourth ventricle and dendrites of neurons in the NTS (nucleus tractus solitarius) and DMN (dorsal motor nucleus) penetrate both the AP and floor of the fourth ventricle. The close proximity of AP to NTS and RVM (rostral ventrolateral medulla) and the existing neural connections provide a way of signaling the SNS and HPA axis. Cytokine-induced production of prostaglandins within the AP, NTS, and RVM may activate the catecholamine projections to the PVN, resulting in subsequent HPA axis activation. This is one possible interaction between the neural and humoral mechanisms of immune to brain communication through which the brain mediates anti-inflammatory responses. Apart from their function in signaling the brain for immunomodulatory responses, cytokines play a multifunctional role in brain injury and neurodegenerative diseases. Restoration of homeostasis as a logical resolution of inflammation does not always occur. For instance, a lack of adequate inflammatory responses may result in increased susceptibility to infections or cancer. On the other hand, excessive responses are associated with autoimmune diseases, diabetes, sepsis, psychiatric diseases with an important inflammatory response like major depression or schizophrenia and other debilitating conditions. When control of local inflammatory responses is lost, pro-inflammatory mediators can spill into the circulation, resulting in systemic inflammation that may progress to shock, multiple organ failure, and death. A recent discovery, showed that a novel neuroimmunomodulatory pathway that interface the brain and the immune system, referred as to the autonomic cholinergic anti-inflammatory pathway, mediate inhibitory responses during inflammation possibly by recruiting central mechanisms that modulate systemic or peripheral inflammatory responses. Still unclear, this neural circuit has been implicated in promoting sort of psychotherapeutical activities such as hypnosis, meditation, prayer, biofeedback, including acupuncture, but this mechanims still remain elusive. The sympathetic and parasympathetic parts of the Autonomic Nervous System rarely operate alone; autonomic responses represent the interplay of both parts. A link between the parasympathetic part of the Autonomic Nervous System and immunoregulatory processes was suggested, when alleviation of T-lymphocyte cytotoxicity by muscarinic cholinergic stimulation was described. Communication between the immune, nervous, and endocrine systems is essential for host defense and involves a variety of mediators including cytokines, neurotransmitters, hormones, and humoral factors. The influence of the brain on immune function and the mechanisms involved in these interactions have been elucidated over the past 3 decades, however, two important questions arise when describing the brain-derived immunomodulation: How is the specific brain initially signaled by cytokines to trigger corresponding neural and neuroendocrine responses?; and: How is immunomodulation achieved through these mechanisms? This review outlines brain-related control mechanisms of immune function in the regulation of inflammation.