Abnormal heart rate variability and atrial fibrillation after aortic surgery / Variabilidade anormal da frequência cardíaca e fibrilação atrial após cirurgia aórtica

Introduction: Complete denervation of transplanted heart exerts protective effect against postoperative atrial fibrillation; various degrees of autonomic denervation appear also after transection of ascending aorta during surgery for aortic aneurysm. Objective: This study aimed to evaluate if the level of cardiac denervation obtained by resection of ascending aorta could exert any effect on postoperative atrial fibrillation incidence. Methods: We retrospectively analysed the clinical records of 67 patients submitted to graft replacement of ascending aorta (group A) and 132 with aortic valve replacement (group B); all episodes of postoperative atrial fibrillation occurred during the 1-month follow-up have been reported. Heart Rate Variability parameters were obtained from a 24-h Holter recording; clinical, echocardiographic and treatment data were also evaluated. Results: Overall, 45% of patients (group A 43%, group B 46%) presented at least one episode of postoperative atrial fibrillation. Older age (but not gender, abnormal glucose tolerance, ejection fraction, left atrial diameter) was correlated with incidence of postoperative atrial fibrillation. Only among a subgroup of patients with aortic transection and signs of greater autonomic derangement (heart rate variability parameters below the median and mean heart rate over the 75th percentile), possibly indicating more profound autonomic denervation, a lower incidence of postoperative atrial fibrillation was observed (22% vs. 54%). Conclusion: Transection of ascending aorta for repair of an aortic aneurysm did not confer any significant protective effect from postoperative atrial fibrillation in comparison to patients with intact ascending aorta. It could be speculated that a limited and heterogeneous cardiac denervation was produced by the intervention, creating an eletrophysiological substrate for the high incidence of postoperative atrial fibrillation observed. .

Introdução: Denervação completa do coração transplantado exerce efeito protetor contra a fibrilação atrial no pós-operatório; vários graus de denervação autonômica aparecem também após a transecção da aorta ascendente durante a cirurgia de aneurisma da aorta. Objetivo: Este estudo teve como objetivo avaliar se o nível de denervação cardíaca obtida por ressecção da aorta ascendente poderia exercer algum efeito sobre a incidência de fibrilação atrial no pós-operatório. Métodos: Foram analisados retrospectivamente os prontuários de 67 pacientes submetidos a enxerto de substituição de aorta torácica (grupo A) e 132 com a substituição da valva aórtica (grupo B). Foram relatados todos os episódios de fibrilação atrial pós-operatória ocorridos durante 1 mês de seguimento. Parâmetros de variabilidade da frequência cardíaca foram obtidos a partir de 24 h de gravação do Holter; dados clínicos, ecocardiográficos e de tratamento também foram avaliados. Resultados: No geral, 45% dos pacientes (grupo A 43%, grupo B 46%) apresentaram pelo menos um episódio de fibrilação atrial no pós-operatório. Idade mais avançada (mas não gênero, tolerância à glicose anormal, fração de ejeção, diâmetro do átrio esquerdo) foi correlacionada com a incidência de fibrilação atrial pós-operatória. Apenas em um subgrupo de pacientes com transecção aórtica e sinais de maior desarranjo autonômico (parâmetros de variabilidade da frequência cardíaca abaixo da mediana e a média de frequência cardíaca acima do percentil 75), indicando possivelmente denervação autonômica mais profunda, foi observada menor incidência de fibrilação atrial pós-operatória (22% vs. 54%). Conclusão: Transecção da aorta ascendente para correção de um aneurisma da aorta não confere qualquer efeito protetor significativo de fibrilação atrial no pós-operatório em comparação com pacientes com aorta ascendente intacta. Pode-se especular que uma denervação cardíaca limitada e heterogênea foi produzida pela ...

Slow axoplasmic transport under scrutiny

The origin of axoplasmic proteins is central for the biology of axons. For over fifty years axons have been considered unable to synthesize proteins and that cell bodies supply them with proteins by a slow transport mechanism. To allow for prolonged transport times, proteins were assumed to be stable, i.e., not degraded in axons. These are now textbook notions that configure the slow transport model (STM). The aim of this article is to cast doubts on the validity of STM, as a step toward gaining more understanding about the supply of axoplasmic proteins. First, the stability of axonal proteins claimed by STM has been disproved by experimental evidence. Moreover, the evidence for protein synthesis in axons indicates that the repertoire is extensive and the amount sizeable, which disproves the notion that axons are unable to synthesize proteins and that cell bodies supply most axonal proteins. In turn, axoplasmic protein synthesis gives rise to the metabolic model (MM). We point out a few inconsistencies in STM that MM redresses. Although both models address the supply of proteins to axons, so far they have had no crosstalk. Since proteins underlie every conceivable cellular function, it is necessary to re-evaluate in-depth the origin of axonal proteins. We hope this will shape a novel understanding of the biology of axons, with impact on development and maintenance of axons, nerve repair, axonopathies and plasticity, to mention a few fields.

El plomo inhibe la corriente activada por protones (ASIC) en las neuronas de los ganglios dorsales / Lead inhibits proton gated currents (ASIC) in dorsal root ganglion neurons

Antecedentes. Los canales iónicos ASIC (del inglés Acid Sensing Ion Channel) son canales iónicos activados por reducciones transitorias en el pH extracelular. Pese a no conocerse con exactitud su mecanismo, la activación ocurre por medio de la unión de protones al dominio extracelular del canal y es modulada por iones calcio y zinc. Objetivo. El hecho de que los cationes divalentes modifiquen el funcionamiento del canal nos llevó a preguntar si el plomo, otro catión divalente, sería capaz de alterar el funcionamiento de los ASIC. Métodos y resultados. Mediante el uso de la técnica de fijación de voltaje en configuración de célula completa en las neuronas de los ganglios de la raíz dorsal de la rata, encontramos que el plomo inhibe la corriente ASIC en forma dependiente de la concentración. Conclusiones. Estos resultados contribuyen a definir los mecanismos de activación de los canales ASIC y a explicar algunos de los mecanismos tóxicos del plomo en el organismo.

BACKGROUND: Acid sensing ion channels (ASIC) are ionic channels activated by transient pH reductions in the ext raceilularenvi ronment. Although the activation mechanism is not fully elucidated, it is clear that the channel is activated by proton binding to its extraceilular domain, a process that is modulated by calcium and zinc. OBJECTIVE: The fact that divalent cations are able to modify ASIC operation, lead us to consider if lead, anotherdivalent cation and widely distributed neurotoxicant, is also capable to affect ASIC function. METHODS: For this purpose, we recordedASiC currents in rat dorsal root ganglion neurons using the whole cell patch-clamp technique. RESULTS: The results indicated that lead inhibits ASIC currents in a concentration -dependent fashion. CONCLUSIONS: These results contribute to the understanding of the activation mechanism of ASIC and to explain some of the toxic mechanisms of lead in the organism.

The extracellular matrix provides directional cues for neuronal migration during cerebellar development

Normal central nervous system development relies on accurate intrinsic cellular programs as well as on extrinsic informative cues provided by extracellular molecules. Migration of neuronal progenitors from defined proliferative zones to their final location is a key event during embryonic and postnatal development. Extracellular matrix components play important roles in these processes, and interactions between neurons and extracellular matrix are fundamental for the normal development of the central nervous system. Guidance cues are provided by extracellular factors that orient neuronal migration. During cerebellar development, the extracellular matrix molecules laminin and fibronectin give support to neuronal precursor migration, while other molecules such as reelin, tenascin, and netrin orient their migration. Reelin and tenascin are extracellular matrix components that attract or repel neuronal precursors and axons during development through interaction with membrane receptors, and netrin associates with laminin and heparan sulfate proteoglycans, and binds to the extracellular matrix receptor integrins present on the neuronal surface. Altogether, the dynamic changes in the composition and distribution of extracellular matrix components provide external cues that direct neurons leaving their birthplaces to reach their correct final location. Understanding the molecular mechanisms that orient neurons to reach precisely their final location during development is fundamental to understand how neuronal misplacement leads to neurological diseases and eventually to find ways to treat them.

An acid-sensing ion channel that detects ischemic pain

Ischemic pain occurs when there is insufficient blood flow for the metabolic needs of an organ. The pain of a heart attack is the prototypical example. Multiple compounds released from ischemic muscle likely contribute to this pain by acting on sensory neurons that innervate muscle. One such compound is lactic acid. Here, we show that ASIC3 (acid-sensing ion channel #3) has the appropriate expression pattern and physical properties to be the detector of this lactic acid. In rats, it is expressed only in sensory neurons and then only on a minority (40 percent) of these. Nevertheless, it is expressed at extremely high levels on virtually all dorsal root ganglion sensory neurons that innervate the heart. It is extraordinarily sensitive to protons (Hill slope 4, half-activating pH 6.7), allowing it to readily respond to the small changes in extracellular pH (from 7.4 to 7.0) that occur during muscle ischemia. Moreover, both extracellular lactate and extracellular ATP increase the sensitivity of ASIC3 to protons. This final property makes ASIC3 a "coincidence detector" of three molecules that appear during ischemia, thereby allowing it to better detect acidosis caused by ischemia than other forms of systemic acidosis such as hypercapnia.

Las neurotrofinas / Neutrophins

Los factores neurotróficos han sido estudiados principalmente en relación con sus funciones en la regulación de los mecanismos moleculares que permiten la supervivencia y diferenciación de poblaciones neuronales específicas durante el desarrollo embrionario. En los últimos años se ha encontrado un creciente número de evidencia experimentales que demuestran las aportaciones fisiológicas de las neurotrofinas a la vida adulta de la neurona, entre las cuales destacan su papel en la plasticidad neuronal, en el mantenimiento de la memoria, en la estimulación de la síntesis y en la liberación de neurotransmisiones y neuropéptidos, y como un mecanismo de protección neuronal ante el daño degenerativo, que incluye el restablecimiento de los axones y de las dendritas, y el mantenimiento de la homeostasis celular. En este trabajo se presentan desde el descubrimiento del Factor de Crecimiento Neuronal hasta los más recientes trabajos de investigación que incluyen todas las neurotrofinas conocidas hasta la fecha. Se hace hincapié en el papel que desempeñan las neurotrofinas con diversas patologías, con el propósito de ofrecer un espectro general de este creciente campo de investigación en la neurobiología contemporánea

Ultimos avances en el síndrome de fragilidad del cromosoma X / Last advances in fragile X chromosome syndrome

The Fragile X syndrome is one of the most frequent forms of mental retardation. The responsible mutation is an unstable repetitive sequence. Since the mutation's discovery, the knowledge about the gene, its protein, function, expression, laboratory detection, phenotype-genotype relationship and risk of expansion, has enormously increased. This work pretends to review the recent advances in this syndrome in all its aspects.