Endogenous angiotensinergic system in neurons of rat and human trigeminal ganglia

To clarify the role of Angiotensin II (Ang II) in the sensory system and especially in the trigeminal ganglia, we studied the expression of angiotensinogen (Ang-N)-, renin-, angiotensin converting enzyme (ACE)- and cathepsin D-mRNA, and the presence of Ang II and substance P in the rat and human trigeminal ganglia. The rat trigeminal ganglia expressed substantial amounts of Ang-N- and ACE mRNA as determined by quantitative real time PCR. Renin mRNA was untraceable in rat samples. Cathepsin D was detected in the rat trigeminal ganglia indicating the possibility of existence of pathways alternative to renin for Ang I formation. In situ hybridization in rat trigeminal ganglia revealed expression of Ang-N mRNA in the cytoplasm of numerous neurons. By using immunocytochemistry, a number of neurons and their processes in both the rat and human trigeminal ganglia were stained for Ang II. Post in situ hybridization immunocytochemistry reveals that in the rat trigeminal ganglia some, but not all Ang-N mRNA-positive neurons marked for Ang II. In some neurons Substance P was found colocalized with Ang II. Angiotensins from rat trigeminal ganglia were quantitated by radioimmunoassay with and without prior separation by high performance liquid chromatography. Immunoreactive angiotensin II (ir-Ang II) was consistently present and the sum of true Ang II (1-8) octapeptide and its specifically measured metabolites were found to account for it. Radioimmunological and immunocytochemical evidence of ir-Ang II in neuronal tissue is compatible with Ang II as a neurotransmitter. In conclusion, these results suggest that Ang II could be produced locally in the neurons of rat trigeminal ganglia. The localization and colocalization of neuronal Ang II with Substance P in the trigeminal ganglia neurons may be the basis for a participation and function of Ang II in the regulation of nociception and migraine pathology.

Effects of chronic baroreceptor stimulation on the autonomic cardiovascular regulation in patients with drug-resistant arterial hypertension

In patients with drug-resistant hypertension, chronic electric stimulation of the carotid baroreflex is an investigational therapy for blood pressure reduction. We hypothesized that changes in cardiac autonomic regulation can be demonstrated in response to chronic baroreceptor stimulation, and we analyzed the correlation with blood pressure changes. Twenty-one patients with drug-resistant hypertension were prospectively included in a substudy of the Device Based Therapy in Hypertension Trial. Heart rate variability and heart rate turbulence were analyzed using 24-hour ECG. Recordings were obtained 1 month after device implantation with the stimulator off and after 3 months of chronic electric stimulation (stimulator on). Chronic baroreceptor stimulation decreased office blood pressure from 185+/-31/109+/-24 mm Hg to 154+/-23/95+/-16 mm Hg (P<0.0001/P=0.002). Mean heart rate decreased from 81+/-11 to 76+/-10 beats per minute(-1) (P=0.001). Heart rate variability frequency-domain parameters assessed using fast Fourier transformation (FFT; ratio of low frequency:high frequency: 2.78 versus 2.24 for off versus on; P<0.001) were significantly changed during stimulation of the carotid baroreceptor, and heart rate turbulence onset was significantly decreased (turbulence onset: -0.002 versus -0.015 for off versus on; P=0.004). In conclusion, chronic baroreceptor stimulation causes sustained changes in heart rate variability and heart rate turbulence that are consistent with inhibition of sympathetic activity and increase of parasympathetic activity in patients with drug-resistant systemic hypertension; these changes correlate with blood pressure reduction. Whether the autonomic modulation has favorable cardiovascular effects beyond blood pressure control should be investigated in further studies.

Cystic adventitial degeneration: ectopic ganglia from adjacent joint capsules

Cystic adventitial degeneration is a rare non-atherosclerotic cause of peripheral arterial occlusive disease, mainly seen in young men without other evidence of vascular disease. Diagnosis will be established by clinical findings and by ultrasound or angiography and can be treated by excision or enucleation of the affected arterial segment or by percutaneous ultrasound-guided aspiration. However, the etiology of adventitial cysts remains unknown. We report a case of cystic adventitial degeneration showing a connection between the joint capsule and the adventitial cyst, supporting the theory that cystic adventitial degeneration may represent ectopic ganglia from adjacent joint capsules.

Autonomic and cardiovascular effects of acute high altitude exposure after myocardial infarction and in normal volunteers

High sympathetic tone creates a significant risk for ventricular arrhythmias and sudden death, which can especially affect patients after a myocardial infarction (MI) when exercising in a hypoxic environment.

A three-dimensional histological atlas of the human basal ganglia. II. Atlas deformation strategy and evaluation in deep brain stimulation for Parkinson disease

OBJECT: The localization of any given target in the brain has become a challenging issue because of the increased use of deep brain stimulation to treat Parkinson disease, dystonia, and nonmotor diseases (for example, Tourette syndrome, obsessive compulsive disorders, and depression). The aim of this study was to develop an automated method of adapting an atlas of the human basal ganglia to the brains of individual patients. METHODS: Magnetic resonance images of the brain specimen were obtained before extraction from the skull and histological processing. Adaptation of the atlas to individual patient anatomy was performed by reshaping the atlas MR images to the images obtained in the individual patient using a hierarchical registration applied to a region of interest centered on the basal ganglia, and then applying the reshaping matrix to the atlas surfaces. RESULTS: Results were evaluated by direct visual inspection of the structures visible on MR images and atlas anatomy, by comparison with electrophysiological intraoperative data, and with previous atlas studies in patients with Parkinson disease. The method was both robust and accurate, never failing to provide an anatomically reliable atlas to patient registration. The registration obtained did not exceed a 1-mm mismatch with the electrophysiological signatures in the region of the subthalamic nucleus. CONCLUSIONS: This registration method applied to the basal ganglia atlas forms a powerful and reliable method for determining deep brain stimulation targets within the basal ganglia of individual patients.

Autonomic stress responses elicited by watching a live broadcast soccer game: a pilot study

Aim: Increased rates of hospitalization due to cardiovascular events have been reported during phases of World Soccer Championships (WSC). The purpose of this pilot study was to explore acute psychological and physiological effects of watching a live broadcast soccer game during the WSC 2006. Methods: Seven male supporters (age: M=24; SD=2.7) of the Swiss National Soccer Team watched a game of their team in a controlled laboratory setting. Heart rate (HR), heart rate variability (HRV), salivary cortisol, alpha-amylase (sAA), and testosterone concentrations, as well as several mood ratings were captured repeatedly before, during, and after the game. Results: Subjects reported feeling stressed, and HR and sAA activity showed an increase during the game. In contrast, HRV, cortisol and testosterone were unaffected. Conclusion: Watching a sports competition seems to specifically affect the sympathetic nervous system, which can be measured by sensitive electrocardiographic and salivary markers.

Autonomic disturbances and cardiovascular reflexes in idiopathic Parkinson's disease

A total of 22 patients suffering from idiopathic Parkinson's disease and 20 age-matched volunteers were questioned about autonomic disturbances and all underwent four non-invasive tests examining cardiovascular reflexes. Significantly more autonomic disturbances were reported by the patients than by the controls. Resting blood pressure was significantly decreased in patients taking dopamine agonists, whereas it was normal in those patients who only received levodopa and anticholinergics. Resting heart rate and resting beat-to-beat variation were normal in the patients, as were the blood pressure response to standing and the postural heart rate response. No pathological response to the Valsalva manoeuvre could be detected. On the other hand, the heart rate variation evoked by deep breathing as well as the blood pressure response and the heart rate response to sustained isometric exercise were significantly diminished in the patients with idiopathic Parkinson's disease. These findings indicate a central disturbance of cardiovascular reflex control, whereas the corresponding peripheral pathways seem to be normal.

Visual avoidance in phobia: particularities in neural activity, autonomic responding, and cognitive risk evaluations.

We investigated the neural mechanisms and the autonomic and cognitive responses associated with visual avoidance behavior in spider phobia. Spider phobic and control participants imagined visiting different forest locations with the possibility of encountering spiders, snakes, or birds (neutral reference category). In each experimental trial, participants saw a picture of a forest location followed by a picture of a spider, snake, or bird, and then rated their personal risk of encountering these animals in this context, as well as their fear. The greater the visual avoidance of spiders that a phobic participant demonstrated (as measured by eye tracking), the higher were her autonomic arousal and neural activity in the amygdala, orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and precuneus at picture onset. Visual avoidance of spiders in phobics also went hand in hand with subsequently reduced cognitive risk of encounters. Control participants, in contrast, displayed a positive relationship between gaze duration toward spiders, on the one hand, and autonomic responding, as well as OFC, ACC, and precuneus activity, on the other hand. In addition, they showed reduced encounter risk estimates when they looked longer at the animal pictures. Our data are consistent with the idea that one reason for phobics to avoid phobic information may be grounded in heightened activity in the fear circuit, which signals potential threat. Because of the absence of alternative efficient regulation strategies, visual avoidance may then function to down-regulate cognitive risk evaluations for threatening information about the phobic stimuli. Control participants, in contrast, may be characterized by a different coping style, whereby paying visual attention to potentially threatening information may help them to actively down-regulate cognitive evaluations of risk.

Autonomic angiotensinergic fibres in the human heart with an efferent sympathetic cophenotype

AIM The autonomic innervation of the heart consists of sympathetic and parasympathetic nerve fibres, and fibres of the intrinsic ganglionated plexus with noradrenaline and acytylcholine as principal neurotransmitters. The fibres co-release neuropeptides to modulate intracardiac neurotransmission by specific presynaptic and postsynaptic receptors. The coexpression of angiotensin II in sympathetic fibres of the human heart and its role are not known so far. METHODS Autopsy specimens of human hearts were studied (n=3; ventricles). Using immunocytological methods, cryostat sections were stained by a murine monoclonal antibody (4B3) directed against angiotensin II and co-stained by polyclonal antibodies against tyrosine hydroxylase, a catecholaminergic marker. Visualisation of the antibodies was by confocal light microscopy or laser scanning microscopy. RESULTS Angiotensin II-positive autonomic fibres with and without a catecholaminergic cophenotype (hydroxylase-positive) were found in all parts of the human ventricles. In the epicardium, the fibres were grouped in larger bundles of up to 100 and more fibres. They followed the preformed anatomic septa and epicardial vessels towards the myocardium and endocardium where the bundles dissolved and the individual fibres spread between myocytes and within the endocardium. Generally, angiotensinergic fibres showed no synaptic enlargements or only a few if they were also catecholaminergic. The exclusively catechalominergic fibres were characterised by multiple beaded synapses. CONCLUSION The autonomic innervation of the human heart contains angiotensinergic fibres with a sympathetic efferent phenotype and exclusively angiotensinergic fibers representing probably afferents. Angiotensinergic neurotransmission may modulate intracardiac sympathetic and parasympathetic activity and thereby influence cardiac and circulatory function.

An Aspect-Oriented Approach for Supporting Autonomic Reconfiguration of Software Architecture

The increasing complexity of current software systems is encouraging the development of self-managed software architectures, i.e. systems capable of reconfiguring their structure at runtime to fulfil a set of goals. Several approaches have covered different aspects of their development, but some issues remain open, such as the maintainability or the scalability of self-management subsystems. Centralized approaches, like self-adaptive architectures, offer good maintenance properties but do not scale well for large systems. On the contrary, decentralized approaches, like self-organising architectures, offer good scalability but are not maintainable: reconfiguration specifications are spread and often tangled with functional specifications. In order to address these issues, this paper presents an aspect-oriented autonomic reconfiguration approach where: (1) each subsystem is provided with self-management properties so it can evolve itself and the components that it is composed of; (2) self-management concerns are isolated and encapsulated into aspects, thus improving its reuse and maintenance. Povzetek: Predstavljen je pristop s samo-preoblikovanjem programske arhitekture.

An autonomic framework for enhancing the quality of data grid services

Data grid services have been used to deal with the increasing needs of applications in terms of data volume and throughput. The large scale, heterogeneity and dynamism of grid environments often make management and tuning of these data services very complex. Furthermore, current high-performance I/O approaches are characterized by their high complexity and specific features that usually require specialized administrator skills. Autonomic computing can help manage this complexity. The present paper describes an autonomic subsystem intended to provide self-management features aimed at efficiently reducing the I/O problem in a grid environment, thereby enhancing the quality of service (QoS) of data access and storage services in the grid. Our proposal takes into account that data produced in an I/O system is not usually immediately required. Therefore, performance improvements are related not only to current but also to any future I/O access, as the actual data access usually occurs later on. Nevertheless, the exact time of the next I/O operations is unknown. Thus, our approach proposes a long-term prediction designed to forecast the future workload of grid components. This enables the autonomic subsystem to determine the optimal data placement to improve both current and future I/O operations.

The change in diastolic blood pressure during autonomic blockade is associated with T50 and error signal in young and older women

Cambios en la presión arterial tras un beta-bloqueante.

A proposal for a modular and application-aware autonomic manager of private cloud infrastructures

Recientemente, el paradigma de la computación en la nube ha recibido mucho interés por parte tanto de la industria como del mundo académico. Las infraestructuras cloud públicas están posibilitando nuevos modelos de negocio y ayudando a reducir costes. Sin embargo, una compañía podría desear ubicar sus datos y servicios en sus propias instalaciones, o tener que atenerse a leyes de protección de datos. Estas circunstancias hacen a las infraestructuras cloud privadas ciertamente deseables, ya sea para complementar a las públicas o para sustituirlas por completo. Por desgracia, las carencias en materia de estándares han impedido que las soluciones para la gestión de infraestructuras privadas se hayan desarrollado adecuadamente. Además, la multitud de opciones disponibles ha creado en los clientes el miedo a depender de una tecnología concreta (technology lock-in). Una de las causas de este problema es la falta de alineación entre la investigación académica y los productos comerciales, ya que aquella está centrada en el estudio de escenarios idealizados sin correspondencia con el mundo real, mientras que éstos consisten en soluciones desarrolladas sin tener en cuenta cómo van a encajar con los estándares más comunes o sin preocuparse de hacer públicos sus resultados. Con objeto de resolver este problema, propongo un sistema de gestión modular para infraestructuras cloud privadas enfocado en tratar con las aplicaciones en lugar de centrarse únicamente en los recursos hardware. Este sistema de gestión sigue el paradigma de la computación autónoma y está diseñado en torno a un modelo de información sencillo, desarrollado para ser compatible con los estándares más comunes. Este modelo divide el entorno en dos vistas, que sirven para separar aquello que debe preocupar a cada actor involucrado del resto de información, pero al mismo tiempo permitiendo relacionar el entorno físico con las máquinas virtuales que se despliegan encima de él. En dicho modelo, las aplicaciones cloud están divididas en tres tipos genéricos (Servicios, Trabajos de Big Data y Reservas de Instancias), para que así el sistema de gestión pueda sacar partido de las características propias de cada tipo. El modelo de información está complementado por un conjunto de acciones de gestión atómicas, reversibles e independientes, que determinan las operaciones que se pueden llevar a cabo sobre el entorno y que es usado para hacer posible la escalabilidad en el entorno. También describo un motor de gestión encargado de, a partir del estado del entorno y usando el ya mencionado conjunto de acciones, la colocación de recursos. Está dividido en dos niveles: la capa de Gestores de Aplicación, encargada de tratar sólo con las aplicaciones; y la capa del Gestor de Infraestructura, responsable de los recursos físicos. Dicho motor de gestión obedece un ciclo de vida con dos fases, para así modelar mejor el comportamiento de una infraestructura real. El problema de la colocación de recursos es atacado durante una de las fases (la de consolidación) por un resolutor de programación entera, y durante la otra (la online) por un heurístico hecho ex-profeso. Varias pruebas han demostrado que este acercamiento combinado es superior a otras estrategias. Para terminar, el sistema de gestión está acoplado a arquitecturas de monitorización y de actuadores. Aquella estando encargada de recolectar información del entorno, y ésta siendo modular en su diseño y capaz de conectarse con varias tecnologías y ofrecer varios modos de acceso. ABSTRACT The cloud computing paradigm has raised in popularity within the industry and the academia. Public cloud infrastructures are enabling new business models and helping to reduce costs. However, the desire to host company’s data and services on premises, and the need to abide to data protection laws, make private cloud infrastructures desirable, either to complement or even fully substitute public oferings. Unfortunately, a lack of standardization has precluded private infrastructure management solutions to be developed to a certain level, and a myriad of diferent options have induced the fear of lock-in in customers. One of the causes of this problem is the misalignment between academic research and industry ofering, with the former focusing in studying idealized scenarios dissimilar from real-world situations, and the latter developing solutions without taking care about how they f t with common standards, or even not disseminating their results. With the aim to solve this problem I propose a modular management system for private cloud infrastructures that is focused on the applications instead of just the hardware resources. This management system follows the autonomic system paradigm, and is designed around a simple information model developed to be compatible with common standards. This model splits the environment in two views that serve to separate the concerns of the stakeholders while at the same time enabling the traceability between the physical environment and the virtual machines deployed onto it. In it, cloud applications are classifed in three broad types (Services, Big Data Jobs and Instance Reservations), in order for the management system to take advantage of each type’s features. The information model is paired with a set of atomic, reversible and independent management actions which determine the operations that can be performed over the environment and is used to realize the cloud environment’s scalability. From the environment’s state and using the aforementioned set of actions, I also describe a management engine tasked with the resource placement. It is divided in two tiers: the Application Managers layer, concerned just with applications; and the Infrastructure Manager layer, responsible of the actual physical resources. This management engine follows a lifecycle with two phases, to better model the behavior of a real infrastructure. The placement problem is tackled during one phase (consolidation) by using an integer programming solver, and during the other (online) with a custom heuristic. Tests have demonstrated that this combined approach is superior to other strategies. Finally, the management system is paired with monitoring and actuators architectures. The former able to collect the necessary information from the environment, and the later modular in design and capable of interfacing with several technologies and ofering several access interfaces.