Opioids in the immune system: from experimental studies to clinical practice

SUMMARY INTRODUCTION: Opioids interact with both innate and adaptive immune systems and have direct effects on opioid receptors located on immune cells. Research on this topic has provided evidence of the opioid influence on the immune response associated with surgical stress. The immunological effects of opioids are currently being investigated, particularly whether they influence the outcome of surgery or the underlying disease regarding important aspects like infection or cancer progression. This review addresses background research related to the influence of the opioid receptor on the immune system, the immunosuppressive effect associated with major opioids during the perioperative period, and their clinical relevance. The objective of the study was to review the effects of opioids on the immune system. Methods: A search strategy was conducted in PubMed, Embase, and the Cochrane databases using the terms "immunosuppression," "immune system," "surgical procedures," "analgesics," "opioids" and "perioperative care." Results: The immunosuppressive effect of opioids was identified over 30 years ago. They include signaling and acting directly through immune cells, including B and T lymphocytes, NK cells, monocytes, and macrophages, as well as activating the downstream pathways of the hypothalamic-pituitary-adrenal (HPA) axis leading to the production of immunosuppressive glucocorticoids in the peripheral and sympathetic nervous system.

RESUMO INTRODUÇÃO: Os opioides interagem com ambos os sistemas imunes, inato e adaptativo, através de efeitos diretos sobre os receptores dos opioides localizados nas células imunes. As pesquisas neste assunto têm fornecido evidência da influência dos opioides sobre a resposta imune associada ao estresse cirúrgico. Os efeitos imunológicos dos opioides estão sendo pesquisados na atualidade, principalmente se eles determinam o resultado da cirurgia ou doença consequente devido a fatos importantes como infecção ou progressão do câncer. Essa revisão tem como alvo ver antecedentes em pesquisa relativa à influência dos receptores dos opioides no sistema imunológico, o efeito imunossupressor associado com opioides maiores durante o período peri-operatório e sua importância clínica. O objectivo da pesquisa foi revisar os efeitos dos opioides no sistema imunológico. MÉTODOS: Uma estrategia de procura foi dirigida na mídia PubMed, e no cadastro de Embase e The Cochrane, usando os termos "imunosuppressão", "sistema imunológico", "procedimentos cirúrgicos", "analgésicos", "opioides" e "cuidado peri-operatório". RESULTADOS: O efeito imunosuppressor dos opioides foi identificado há mais de 30 anos. Os efeitos imunosupressores incluem sinalização e ação diretamente através das células imunes, mesmo com os linfócitos B e T, células NK, monócitos e macrófagos, também como ativando as vias de corrente do eixo hipotálamo- hipófise- adrenal (HPA) levando à produção de glucocorticoides imunossupresores no sistema nervoso periférico e simpático.

Efectos de múltiples exposiciones a sevoflurano a dosis sub-CAM en la neuroapoptosis y la función cognitiva en el periodo neonatal / Effects of multiple exposures to sevoflurane at sub-MAC doses on neuroapoptosis and cognitive function during the neonatal period

Introducción: Recientes estudios han sugerido que los niños con múltiples exposiciones anestésicas tienen un mayor riesgo de deterioro neurocognitivo. Objetivo: Analizar los efectos neurodegenerativos a nivel histológico, cognitivo y del comportamiento posterior a exposiciones repetidas al sevoflurano a dosis inferiores a la concentración alveolar minina en ratas neonatales. Métodos: Se expusieron ratas Wistar de 5-7 días durante una hora a sevoflurano al 2,3%; una, 2 o 3 veces con intervalos de 24 h entre exposición. Posteriormente se determinó el efecto del anestésico en la neuroapoptosis mediante marcación inmunohistoquímica con caspasa-3, Fox-3 y CD95. El aprendizaje fue evaluado con el laberinto acuático de Morris, y el comportamiento relacionado a ansiedad, con laberinto elevado en cruz. Resultados: En todos los grupos experimentales se evidenció apoptosis neuronal medida por caspasa-3, siendo más marcada en el grupo de sevoflurano y en grupos de primera exposición. En laberinto elevado en cruz se encontró un tiempo total de permanencia en brazos abiertos (t test p = 0,113) estadísticamente no significativo con respecto al grupo control. En el laberinto acuático de Morris se encontró diferencia estadísticamente significativa (t test p < 0,001) cuando se compara el tiempo de realización de la prueba con respecto al grupo control. Conclusiones: La exposición a sevoflurano en ratas neonatales durante periodos cortos y repetidos induce muerte neuronal posiblemente por apoptosis a través de la activación de caspasa-3. Como consecuencia produce déficit de aprendizaje, principalmente en la adquisición de memoria espacial.

Introduction: Recent studies have suggested that children who are exposed multiple times to anesthesia have an increased risk of neurocognitive impairment. Objective: To analyze at a histological level the neurodegenerative, cognitive and behavioral effects following repeated exposures to sevoflurane at doses below the minimum alveolar concentration in neonatal rats. Methods: Wistar rats were exposed to 2.3% sevoflurane, one, two or three times for 1 h, in the course of 5-7 days, with 24-h intervals between each exposure. The neuroapoptotic effect of the anesthetic agent was subsequently determined using immunohistochemical labeling with caspase-3, Fox-3 and CD95. Learning was assessed with the Morris Water Maze, and the anxiety-related behavior was assessed with the Elevated Plus-Maze. Results: Every experimental group showed evidence of neuronal apoptosis measured withcaspase-3; however, the apoptosis was more evident in the sevoflurane group and in the first exposure groups. The total time spent in the open arms of the Elevated Plus-Maze (t test p = 0.113) was not statistically significant as compared to the control group. When comparing the test time vs. the control group, the Morris Water Maze showed a statistically significant difference (t test p < 0.001). Conclusions: Sevoflurane exposure of neonate rats for short and repeated time intervals induces neuronal death probably due to apoptosis, through caspase-3 activation. This results in learning deficit, particularly in terms of spatial memory acquisition.

Morfología dental en dentición mixta: correlación de tres rasgos morfológicos en dientes temporales y permanentes de escolares de Cali, Colombia / Mixed dentition Morphology characteristics: a correlation between 3 non-metric dental traits in temporal and permanent dentition in scholars from Cali - Colombia

Objetivo: Determinar la correlación entre la frecuencia y la variabilidad de tres rasgos morfológicos dentales coronales (cúspide de Carabelli, protostilido y patrón cúspideo) entre los dientes temporales (um2/ lm2) y permanentes (UM1/LM1), con el fin de establecer la posible correlación de con su expresión o manifestación clínica. Materiales y Métodos: En modelos de yeso obtenidos de impresiones tomadas a 100 escolares de ambos sexos, estudiantes de tres colegios de Cali-Colombia, que presentaban dentición mixta con primeros molares permanentes y segundos molares temporales presentes en boca y pertenecían a un grupo de población mestiza, se realizó un estudio descriptivo cuantitativo para caracterizar la morfología dental mediante el sistema de placas ASU y los Métodos de Grine y de Sciulli. Resultados: La alta prevalencia de las formas del surco y de la fosa de la Cúspide de Carabelli, la alta frecuencia del protostílido en grado 1 (foramen secum) y el comportamiento de la expresión del patrón cuspídeo, evidenciaron que la población objeto de estudio ha recibido influencia de los complejos dentales mongoloide y caucasoide. Se hizo indudable la correspondencia en las formas de manifestación en ambas denticiones, y se observó simetría bilateral y que no se presenta dimorfismo sexual en los rasgos morfológicos dentales estudiados.

Objectives: Determine the correlation of the frequency and variability of three Non-metric dental crown traits (Carabellicusp, protostylid and molar pattern cusp) between deciduous (um2/lm2) and permanent (UM1/LM1) teeth in mixed-dentition subjects. Materials and methods: A descriptive study was conducted to determine the dental morphology in mixed dentition stage of young subjects. The Arizona State University Dental Anthropology System ASUDAS and Grind and Sciulli Methods were used as reference to compare frequency of dental traits in dental casts of 100 young individuals racially mixed. Results: A high expression of furrows and pits of the Carabelli cusp, a high frequency of protostylid in degree 1 (foramen secum) and a expression of molar pattern cusp, revealed that the studied population received influences of the Mongoloid and Caucasoid dental complexes. Correspondence on the traits expression among temporal and permanent dentition was also confirmed. Bilateral symmetry and sexual dimorphism in the analyzed non-metric dental crown traits were found.