O hormônio tireoidiano (HT) é essencial para o desenvolvimento, maturação e metabolismo ósseos, enquanto que o sistema nervoso simpático (SNS) é, também, um potente regulador do remodelamento ósseo. Demonstrou-se que SNS regula negativamente a massa óssea, agindo via receptores ?2-adrenérgicos (?2-AR), expressos em osteoblastos. O nosso grupo demonstrou que os receptores ?2 adrenérgicos (?2-AR) também medeiam ações do SNS no esqueleto e que são expressos em osteoblastos, osteócitos, condrócitos e osteoclastos. Considerando-se que o HT interage com o SNS para regular uma série de processos fisiológicos, e que o excesso de HT e a ativação do SNS causam perda de massa óssea, levantamos a hipótese de que há interação entre o HT com o SNS para regular a massa óssea. Estudos do nosso grupo vêm sustentando essa hipótese, uma vez que camundongos com inativação gênica dos receptores beta2-AR apresentam resistência à osteopenia induzida por doses tóxicas de HT. Considerando-se, ainda, que a interação do HT com o SNS em vários tecidos e/ou órgãos depende da sinalização beta2 adrenérgica, o presente estudo teve como objetivo avaliar se a interação do HT com o SNS para regular a morfofisiologia óssea envolve o beta2-AR. Para tanto, estudamos o efeito de 10x e 20x a dose fisiológica de triiodotironina (3,5ug ou 7.0ug de T3/100g de massa corporal/dia, respectivamente), por 90 dias, na microaquitetura óssea e em parâmetros biomecânicos do fêmur de camundongos com inativação gênica do beta2-AR (beta2-AR-/-), e nos seus respectivos Selvagens (Selv), os camundongos da linhagem FVB. Como esperado, o tratamento com T3 promoveu efeitos deletérios na microarquitetura trabecular das fêmeas Selv, enquanto alguns desses efeitos foram mais brandos ou inexistentes nos animais beta2-AR-/-, revelando resistência do osso trabecular dos animais knockout (KO) aos efeitos deletérios da tireotoxicose. Em contraste, a microarquitetura femoral dos camundongos machos beta2-AR-/- se mostrou mais sensível aos efeitos deletérios da tireotoxicose, em relação aos respectivos Selv. Quanto ao osso cortical femoral, vimos que o tratamento com T3 aumentou o perímetro endosteal e a área medular nos animais Selv machos e fêmeas, mas não nos animais beta2-AR-/-, o que sugere que o T3 promove reabsorção óssea endosteal no osso cortical, em um mecanismo que depende da via de sinalização do beta2-AR. Vimos, ainda, que o tratamento com T3 causou reduções significativas na carga máxima, tenacidade, rigidez e resiliência do fêmur dos camundongos fêmeas Selv. Em contraste, nenhum desses parâmetros biomecânicos foi afetado pelo tratamento com T3 no fêmur das fêmeas KO, evidenciando, mais uma vez, uma resistência desses animais aos efeitos deletérios da tireotoxicose no tecido ósseo. Por outro lado, os camundongos machos Selv e KO se mostraram resistentes aos efeitos deletérios do tratamento com T3 sobre os parâmetros biomecânicos do fêmur, sugerindo a participação de fatores sexuais na interação do HT com o SNS para regular a morfofisiologia óssea. Em conjunto, os achados do presente estudo corroboram a hipótese de que o HT interage com o SNS através da via dos receptores beta2 adrenérgicos para regular a morfofisiologia óssea, especialmente em fêmeas e no osso cortical / Thyroid hormone (TH) is essential for bone development, maturation and metabolism, while the sympathetic nervous system (SNS) is also a potent regulator of bone remodeling. SNS has been shown to negatively regulate bone mass, acting via beta2-adrenergic (beta2-AR) receptors expressed in osteoblasts. Our group demonstrated that alpha2-adrenergic (alpha2-AR) receptors also mediate SNS actions in the skeleton and are expressed in osteoblasts, osteocytes, chondrocytes and osteoclasts. Considering that TH interacts with the SNS to regulate a series of physiological processes, and that the excess of TH and the activation of the SNS cause loss of bone mass, we hypothesize that there is interaction between TH and the SNS to regulate the bone mass. Studies of our group have supported this hypothesis, since mice with gene inactivation of alpha2-AR present resistance to the osteopenia induced by toxic doses of TH. Considering that the TH-SNS interaction in various tissues and/or organs depends on beta2-adrenergic signaling, the present study aimed to evaluate whether the interaction of TH with the SNS to regulate the bone morphophysiology involves beta2- AR. Therefore, we studied the effect of 10x and 20x the physiological dose of triiodothyronine (3.5ug or 7.0ug of T3/100g body mass/day, respectively), for 90 days, in the bone microarchitecture and biomechanical parameters of the femur mice with beta2-AR gene inactivation (beta2-AR-/-), and of their respective Wild-type (WT) controls, the FVB lineage mice. As expected, T3 treatment promoted deleterious effects on the trabecular microarchitecture of the WT females, while some of these effects were milder or nonexistent in beta2-AR-/- animals, revealing trabecular bone resistance of knockout (KO) animals to the deleterious effects of thyrotoxicosis. In contrast, the femoral microarchitecture of the male beta2-AR-/- mice was more sensitive to the deleterious effects of thyrotoxicosis, in relation to the respective WT animals. Regarding to the femoral cortical bone, we saw that T3 treatment increased the endosteal perimeter and the medullary area both male and female WT animals, but not in the beta2-AR-/- mice, suggesting that T3 promotes endosteal bone resorption in the cortical bone, in a mechanism that depends on the alpha2-AR signaling pathway. We also found that treatment with T3 caused significant reductions in the maximum load, tenacity, stiffness and resilience of femurs of the WT female mice. In contrast, none of these biomechanical parameters was affected by T3 treatment in the KO females, demonstrating again resistance of these animals to the deleterious effects of thyrotoxicosis on bone tissue. On the other hand, WT and KO male mice were resistant to the deleterious effects of T3 treatment on the biomechanical parameters of the femur, suggesting the participation of sexual factors in the interaction of HT with the SNS to regulate bone morphophysiology. Taken together, the findings of the present study corroborate the hypothesis that TH interacts with the SNS through the beta2 adrenergic receptor pathway to regulate bone morphophysiology, especially in females and cortical bone

Obesity-associated metabolic disorders are amongst the most prevalent causes of death worldwide. Understanding how obesity leads to the development of the Metabolic Syndrome (MetS) and cardiovascular disease (CVD) will enable the development of novel therapies that dissociate obesity from its cardiometabolic complications. Our laboratory views the functional capacity of white adipose tissue (WAT), the organ designed for safe lipid storage, as a key factor in the development of MetS and CVD. At a genetically-defined stage of the aberrant WAT expansion that occurs during obesity, adipocytes undergo a functional failure, resulting in an impaired control of serum free fatty acid (FFA) concentration. In such setting, FFAs and their metabolic derivatives accumulate in other organs, where they cause lipotoxicity, leading to the development of insulin resistance and CVD. We therefore aim to understand the pathophysiological mechanisms that induce adipocyte dysfunction. The past two decades of research have established the immune system as an important regulator of WAT function. The number of adipose tissue macrophages (ATMs), the most abundant immune cell type in WAT, increases during obesity, resulting in WAT inflammation. Multiple genetic and pharmacological intervention studies of murine models of obesity have assigned a causal link between ATM pro-inflammatory activation and WAT dysfunction. However, while the propagation of inflammation in ATMs during obesity has been extensively studied, factors triggering ATM inflammatory activation are less clear. Recently, our lab has observed lipid accumulation in the ATMs isolated from obese mice. Lipid-laden ATMs were pro-inflammatory, leading us to hypothesise that aberrant lipid build-up in macrophages triggers WAT inflammation during obesity. This thesis expands on the initial findings from our lab and describes two novel mechanisms that potentially contribute to lipid-induced inflammatory activation of ATMs. In chapter 3, the role of de novo phosphatidylcholine (PC) synthesis pathway during lipotoxicity in macrophages is addressed. The first part of the chapter demonstrates that lipotoxic environment increased de novo PC synthesis rate in bone marrow-derived macrophages (BMDMs) and ATMs, and that loss of rate-limiting enzyme in de novo PC synthesis pathway, CTP:phosphocholine cytidylyltransferase a (CCTa) diminished saturated FFA-induced inflammation in BMDMs. In the second part, I show that macrophage-specific CCTa deletion did not impact on the development of WAT inflammation or systemic insulin resistance, but had a minor benefitial effect on hepatic gene transcription during obesity. Chapter 4 develops on recent observations of interactions between sympathetic nerves and macrophages in WAT. In the first part of the chapter, I demonstrate that stimulating B2-adrenergic receptor (B2AR), the main receptor for sympathetic neurotransmitter norepinephrine in macrophages, enhanced intracellular triglyceride storage by up-regulating diacylglycerol O-acyltransferase 1 (Dgat1) gene expression in BMDMs. The second part of the chapter shows that macrophage-specific B2AR deletion did not modulate systemic glucose and lipid metabolism during obesity, but mice lacking B2ARs in macrophages demonstrated augmented hepatic glucose production on a chow diet. Furthermore, systemic B2AR blockade or macrophage-specific B2AR deletion in mice did not affect the thermogenic response to cold exposure. Chapter 5 includes the characterisation of B2AR stimulation-induced changes to the global cellular proteome of BMDMs, and a subsequent validation of the role of candidate transcription factors in regulating B2AR agonism-induced gene expression in BMDMs.

Introdução. Apneia obstrutiva do sono (AOS) provoca alterações autonômicas, tais como, hipersensibilidade quimiorreflexa e diminuição da sensibilidade barorreflexa e metaborreflexa muscular que contribuem para a hiperativação simpática em indivíduos que sofrem desse distúrbio. O objetivo desse estudo foi avaliar o efeito do treinamento físico no controle metaborreflexo da atividade nervosa simpática muscular (ANSM) em indivíduos com apneia obstrutiva do sono. Métodos. Todos os indivíduos triados para este estudo foram submetidos à polissonografia noturna convencional e avaliação da capacidade cardiorrespiratória em esforço. Quarenta e um adultos sedentários com AOS moderada e severa foram aleatoriamente divididos em grupo não-treinado (AOSNT, n=21) e treinado (AOST, n=20). A ANSM foi avaliada pela técnica microneurografia, o fluxo sanguíneo muscular (FSM) por pletismografia de oclusão venosa, a frequência cardíaca (FC) pelo eletrocardiograma e a pressão arterial (PA) método oscilométrico automático. Todas as variáveis fisiológicas foram avaliadas simultaneamente durante quatro minutos de repouso, seguido de três minutos de exercício isométrico de preensão manual a 30% da contração voluntária máxima, seguido por dois minutos de oclusão circulatória pós-exercício (OCPE) do segmento corporal previamente exercitado. A ativação seletiva do controle metaborrelfexo foi calculada pela diferença da ANSM do primeiro e segundo minutos da OCPE e a média da ANSM no repouso. Resultados. Os grupos foram semelhantes em gênero, idade, parâmetros antropométricos, parâmetros neurovasculares, parâmetros hemodinâmicos e parâmetros do sono. O treinamento físico reduziu a ANSM e aumentou o FSM no repouso. O treinamento físico diminuiu significativamente os níveis de ANSM e aumentou a resposta de FSM durante o exercício isométrico de preensão manual. O treinamento físico não alterou as respostas de frequência cardíaca e de PA durante o exercício isométrico. Em relação à sensibilidade metaborreflexa, o treinamento físico aumentou significativamente as respostas da ANSM no 1º minuto de OCPE. Não foram observadas diferenças significativas no FSM, FC e PA após o treinamento físico. Conclusões. O treinamento físico aumenta a sensibilidade metaborreflexa muscular em indivíduos com AOS, o que pode contribuir, pelo menos em parte, para a melhora no controle neurovascular durante o exercício nesses pacientes / Introduction. Obstructive sleep apnea (OSA) causes autonomic dysfunction, such as, chemoreflex hypersensitivity and baroreflex impairment and muscle metaboreflex decrease, which contribute to sympathetic overactivity in subjects who suffer from this disturbance. The purpose of this study was evaluated the effect of exercise training on muscle metaboreflex control of muscle sympathetic nerve activity (MSNA) in subjects with OSA. Methods. All individuals selected for this study underwent overnight polysomnography and cardiopulmonary exercise testing. Forty-one untrained adults with moderate to severe OSA were randomly divided into non-trained (AOSNT, n=21) and trained (AOST, n=20) groups. MSNA was assessed by microneurography technique, muscle blood flow (FBF) by venous occlusion plethysmography, heart rate (HR) by electrocardiography and blood pressure (BP) by noninvasively automated oscillometric device. All physiological variables were simultaneously assessed for 4 minutes at rest, followed by three minutes of isometric handgrip exercise at 30% of maximal voluntary contraction, followed by two minutes of postexercise regional circulatory arrest (PECA). Muscle metaboreflex sensitivity was calculated as the difference in MSNA at first and second minute of PECA and MSNA at rest period. Results. AOSNT and AOST groups were similarly in gender, age, anthropometric, neurovascular, hemodynamic and sleep parameters. Exercise training reduced MSNA and increased FBF. Exercise training significantly reduced MSNA levels and increased FBF responses during isometric handgrip exercise. Regarding the metaboreflex sensitivity, exercise training significantly increased MSNA response at 1st minute of PECA. There were no significantly difference in FBF, HR and BP after exercise training. Conclusions. Exercise training increases muscle metaboreflex sensitivity in patients with OSA, which seems to contribute, at least in part, to the improvement in neurovascular control during exercise in these patients

Les anomalies du système nerveux sympathique (SNS) contribuent au développement de certaines pathologies cardiovasculaires comme l'insuffisance cardiaque (IC) et les cardiomyopathies de stress. Ces anomalies impliquent une activation persistante, défavorable du SNS dans l'IC et une activation sympathique épisodique dans les cardiomyopathies de stress. Le rôle du SNS au cours des cardiopathies valvulaires reste quand à lui encore mal connu. Notre travail de thèse avait pour objectif d'analyser par microneurographie l'activité du SNS et sa modulation par les arcs réflexes physiologiques, au cours de l'IC avec ou sans comorbidités (notamment l'anémie, l'insuffisance rénale) ainsi qu'au cours des cardiomyopathies de stress et de la sténose aortique. L'hyperactivité du SNS participe à l'initiation et à la progression de l'IC et constitue un marqueur pronostique mais aussi une cible thérapeutique. Les mécanismes fondamentaux qui sous-tendent l'activation du SNS au cours de l'IC restent encore incertains. Une hypothèse engloberait une diminution des réflexes inhibiteurs, comme le baroréflexe artériel périphérique et une augmentation des réflexes excitateurs, comme le chémoréflexe artériel périphérique. Avec notre premier travail nous rapportons que l'augmentation de l'activité du chémoréflexe périphérique diminue directement la fonction du baroréflexe artériel chez les patients IC et que cette interaction contribue à l'hyperactivité sympathique. Notre équipe avait déjà démontré qu'au cours de l'IC, l'insuffisance rénale (IR) et l'anémie contribuent à l'augmentation de l'activité du SNS. Bien que la dysfonction rénale et l'anémie aient été largement étudiées séparément dans l'IC, des données épidémiologiques suggèrent également que l'IR peut coexister avec l'anémie chez les patients atteints d'IC dans ce qu'on désigne par le "syndrome d'anémie cardio-rénale". Nous avons démontré que ce syndrome au cours de l'IC est associé à une hyperactivité sympathique médiée à la fois par une activation tonique du chémoréflexe périphérique et une atténuation du baroréflexe artériel. Le syndrome du Tako Tsubo est une cardiomyopathie de stress caractérisée par une insuffisance ventriculaire gauche aiguë réversible. La physiopathologie exacte reste inconnue, mais l'hyperactivation sympathique semble jouer un rôle fondamental. Nous avons démontré par microneurographie la présence d'une hyperactivation du SNS dans la phase subaiguë de la maladie associée à une altération du baroréflexe périphérique. La sténose aortique (SA) est, dans les pays développés, la plus fréquente de toutes les maladies cardiaques valvulaires. Le remplacement valvulaire aortique transcathéter (TAVI) est une option thérapeutique émergente chez les patients avec une SA sévère symptomatique à haut risque chirurgical. La SA est associée à une morbi-mortalité cardiovasculaire accrue. Nous avons souhaité apprécier si au cours de la SA il existait une hyperactivité du SNS qui pouvait contribuer à expliquer le pronostic réservé des patients et être la cible du TAVI. Nous avons montré que les patients atteints de SA ont une activité du SNS augmentée et qui est associée à une diminution du gain du baroréflexe périphérique. Le TAVI normalise ces paramètres. Au total, ce travail de thèse a permis d'identifier de nouveaux mécanismes contribuant à l'hyperactivité du tonus sympathique au cours de l'insuffisance cardiaque, de la sténose aortique et de la cardiomyopathie du Tako Tsubo. L'hyperactivité du SNS jouant un rôle critique dans l'insuffisance cardiaque, la connaissance des mécanismes physiopathologiques qui la sous-tendent pourrait permettre l'identification et/ou la validation de nouvelles stratégies pour son traitement. / Sympathetic nervous system (SNS) abnormalities contribute to the development of some cardiovascular diseases such as heart failure (HF) and stress cardiomyopathies. These abnormalities involve persistent, adverse activation of SNS in HF and episodic sympathetic activation in stress cardiomyopathies. Less is still known about the role of SNS in valvular heart diseases. Our PhD work had as a purpose to analyse, by microneurography, the activity of SNS and its modulation by physiological reflex arcs, during HF, with and without comorbidities (including anemia and kidney failure), in stress cardiomyopathies and during aortic stenosis. SNS hyperactivity participates in the initiation and progression of HF being also a prognostic marker and a therapeutic target. The fundamental mechanisms underlying the activation of SNS in HF remain uncertain. One hypothesis would include a decrease in inhibitory reflexes activity, such as peripheral arterial baroreflex and an increase in excitatory reflexes activity, such as peripheral arterial chemoreflex. With our first work we report that the increased activity of peripheral chemoreflex directly decreases the arterial baroreflex function in HF patients and that this interaction contributes to sympathetic hyperactivity. Our team had already shown that during HF, renal dysfunction and anemia contribute to the increased activity of SNS. Although renal dysfunction and anemia have been widely studied separately in HF, epidemiological data also suggest that renal impairment can coexist with anemia in HF patients in the so called "cardio-renal anemia syndrome". We demonstrated that this syndrome during HF is associated with elevated sympathetic activity mediated by both tonic peripheral chemoreflex activation and arterial baroreflex impairment.The Tako Tsubo (TTC) is a stress cardiomyopathy characterized by acute reversible left ventricular failure. The exact pathophysiology remains unknown but sympathetic hyperactivation seems to play a fundamental role. We reported by microneurography the presence of SNS hyperactivation in the subacute phase of the disease associated with impairment in arterial baroreflex.In developed countries, aortic stenosis (AS) is the most prevalent of all valvular heart diseases. Transcatheter aortic valve implantation (TAVI) is an emerging therapeutic option in symptomatic patients with severe AS at high surgical risk. AS is associated with increased cardiovascular morbidity and mortality. We wanted to assess whether in AS sympathetic hyperactivity existed that could help to explain the poor prognosis of these patients and be the target of TAVI. We have shown that AS patients have an increased SNS activity that is associated with reduced peripheral baroreflex gain. The TAVI normalizes these parameters.On the whole this PhD work identified new mechanisms that contribute to SNS hyperactivity in heart failure, aortic stenosis and Tako Tsubo cardiomyopathy. Since SNS hyperactivity plays a critical role in heart failure, knowledge of the pathophysiological mechanisms that underlie it could allow identification and/or validation of new strategies for its treatment.

Thesis (Ph.D. (Electronical Engineering))--North-West University, Potchefstroom Campus, 2008.

Subjects participating in magnetic resonance imaging (MRI) examinations regularly report anxiety and stress related reactions. This may result in impaired data quality and premature termination of scans. Moreover, cognitive functions and neural substrates can be altered by stress. While prior studies investigated pre–post scan differences in stress reactions only, the present study provides an in-depth analysis of mood changes and hormonal fluctuations during the time course of a typical fMRI session. Thirty-nine subjects participated in the study. Subjective mood, salivary alpha-amylase (sAA) and cortisol were assessed at six time points during the lab visit. Associations between hormonal data and neural correlates of a visual detection task were observed using a region of interest approach applied to the thalamic region. Mood and hormonal levels changed significantly during the experiment. Subjects were most nervous immediately after entering the scanner. SAA was significantly elevated after MRI preparation. A subgroup of n = 5 (12.8%) subjects showed pronounced cortisol responses exceeding 2.5 nmol/l. Preliminary fMRI data revealed an association between sAA levels and left thalamic activity during the first half of the experiment that disappeared during the second half. No significant correlation between cortisol and thalamic activity was observed. Results indicate that an fMRI experiment may elicit subjective and neuroendocrine stress reactions that can influence functional activation patterns.

The central nervous system is largely responsible for receiving sensory information from the environment and determining motor output. Yet, centrally-derived behavior and sensation depends on the optimal maintenance of the cells, tissues, and organs that feed and support these functions. Most of visceral regulation occurs without conscious oversight, making the spinal cord a key site for integration and control. How the spinal cord modulates output to our organs, or sensory information from them, is poorly understood. The overall aim of this dissertation was to better understand spinal processing of both visceral sensory information to and sympathetic output from the spinal cord. I first established and validated a HB9-GFP transgenic mouse model that unambiguously identified sympathetic preganglionic neurons (SPNs), the spinal output neurons for the sympathetic nervous system. Using this model, I investigated the electrophysiological similarities and diversity of SPNs, and compared their active and passive membrane properties to those in other animal models. My results indicate that while many of the same characteristics are shared, SPNs are a heterogeneous group that can be differentiated based on their electrophysiological properties. Since descending monoaminergic pathways have particularly dense projections to sympathetic regions of the spinal cord, I next examined the modulatory role that the monoamines have on spinal sympathetic output. While each neuromodulator tested had a unique signature of action, serotonin and norepinephrine appeared to increase the excitability of individual SPNs, while dopamine had more mixed actions. Since many autonomic reflexes are integrated by the spinal cord, I also questioned whether these reflexes would be similarly modulated. I therefore developed a novel in vitro spinal cord and sympathetic chain preparation, which allowed for the investigation of visceral afferent-mediated reflexes and their neuromodulation by monoamines. This preparation exposed a dichotomy of action, where sympathetic and somatic motor output is generally enhanced by the monoamines, but reflexes mediated by visceral input are depressed. Utilizing the spinal cord and sympathetic chain preparation, I also investigated how the spinal cord modulates visceral sensory information. One of the most powerful means of selectively inhibiting afferent information from reaching the spinal cord is presynaptic inhibition. I hypothesized that both spinal visceral afferents and descending monoaminergic systems would depress transmission of visceral afferents to the spinal cord. My results demonstrated that activity in spinal visceral afferents can lead to spinally generated presynaptic inhibition, and that in addition to depressing synaptic transmission to the spinal cord, the monoamines also depress the intrinsic circuitry that generates this activity-dependent presynaptic inhibition. Taken together, my results indicate that descending monoaminergic pathways act to limit the amount of visceral sensory information reaching the central nervous system and increase sympathetic output, resulting in an uncoupling of output from visceral sensory input and transitioning to a feed-forward, sympathetically dominant control strategy. This combination offers complex modulatory strategies for descending systems.

The rapid growth of biotechnology has promoted industries to harness the market in the field of human energy systems. A growing literature of research has linked human energy systems to weight loss, major diseases or illnesses. In our modern society, the general public is exposed to everyday stress, which often results in the development of chronic stress. Therefore, stress becomes an important area of medicine. It has been postulated that suppressing these physiological responses may help in disease prevention. Consequently, there is an urge for defining a model integrating stress with the human energy model. Over the past decades, a large amount of research has been put forward in defining the physiological responses or changes when an individual experiences psychological or environmental changes such as interpersonal dysfunction, traumatic experiences and diseases. Interestingly, it reveals that blood glucose fluctuation tends to be the end product of most psychological or physiological stressors. The blood glucose system is one of the major subsystems of the complete metabolic fuel system in humans. In this study, an empirical model and procedure for the derivation of the model due to various psychological influences on the human energy system are presented. This study can be divided into two main sections. An overview of a previously developed unit (ets: equivalent teaspoon sugar) for blood glucose quantification is given in the first section. Stress quantification methods are derived in the second section and a link between these methods and ets is drawn. A verification study of the derived model is also presented in the second section. Stress can be divided into physiological stress and psychological stress. Between the two types of stress, a generalised model based on studies of physiological stress has been drawn and accepted by the public. However, the generalised model does not account for psychological stress. Evidence shows that depending on the specific nature of a stressful circumstance, it can cause different activations of central circuits leading to the release of different neurotransmitters. However, these neurotransmitters have a common effect of increasing blood glucose concentrations. A substantial amount of literature shows that, when stress involves mental effort, epinephrine (EPI) is the main endocrine response. However, stress that does not require mental effort mainly induces cortisol release. The response models for different types of stress were derived using these relations. Furthermore, it is known that prolonged stress may lead to the development of disease. Several studies have used this observation and associated chronic stress with the relative risk factor of cardiovascular disease (CVD). Previously, different quartiles of risk factors for CVD have been related to blood glucose energy and ets expenditure. This link was further utilised to quantify chronic stress in this study. Increases in either of the two endocrine concentrations have been shown to raise the blood glucose level. In order to demonstrate the benefits of applying the ets concept, the cortisol and epinephrine responses were further quantified using the new glucose quantification method, the equivalent teaspoon sugar (ets) concept. The models derived in this study were verified against measured data. The models reveal a strong agreement with the measured data and therefore support the feasibility of these quantification methods. In conclusion, a link does exist between blood glucose energy and stress, and the highly accurate models derived for this association may serve as an adjunct tool for glycaemic control and stress management. / Thesis (Ph.D. (Electronical Engineering))--North-West University, Potchefstroom Campus, 2008.

The rapid growth of biotechnology has promoted industries to harness the market in the field of human energy systems. A growing literature of research has linked human energy systems to weight loss, major diseases or illnesses. In our modern society, the general public is exposed to everyday stress, which often results in the development of chronic stress. Therefore, stress becomes an important area of medicine. It has been postulated that suppressing these physiological responses may help in disease prevention. Consequently, there is an urge for defining a model integrating stress with the human energy model. Over the past decades, a large amount of research has been put forward in defining the physiological responses or changes when an individual experiences psychological or environmental changes such as interpersonal dysfunction, traumatic experiences and diseases. Interestingly, it reveals that blood glucose fluctuation tends to be the end product of most psychological or physiological stressors. The blood glucose system is one of the major subsystems of the complete metabolic fuel system in humans. In this study, an empirical model and procedure for the derivation of the model due to various psychological influences on the human energy system are presented. This study can be divided into two main sections. An overview of a previously developed unit (ets: equivalent teaspoon sugar) for blood glucose quantification is given in the first section. Stress quantification methods are derived in the second section and a link between these methods and ets is drawn. A verification study of the derived model is also presented in the second section. Stress can be divided into physiological stress and psychological stress. Between the two types of stress, a generalised model based on studies of physiological stress has been drawn and accepted by the public. However, the generalised model does not account for psychological stress. Evidence shows that depending on the specific nature of a stressful circumstance, it can cause different activations of central circuits leading to the release of different neurotransmitters. However, these neurotransmitters have a common effect of increasing blood glucose concentrations. A substantial amount of literature shows that, when stress involves mental effort, epinephrine (EPI) is the main endocrine response. However, stress that does not require mental effort mainly induces cortisol release. The response models for different types of stress were derived using these relations. Furthermore, it is known that prolonged stress may lead to the development of disease. Several studies have used this observation and associated chronic stress with the relative risk factor of cardiovascular disease (CVD). Previously, different quartiles of risk factors for CVD have been related to blood glucose energy and ets expenditure. This link was further utilised to quantify chronic stress in this study. Increases in either of the two endocrine concentrations have been shown to raise the blood glucose level. In order to demonstrate the benefits of applying the ets concept, the cortisol and epinephrine responses were further quantified using the new glucose quantification method, the equivalent teaspoon sugar (ets) concept. The models derived in this study were verified against measured data. The models reveal a strong agreement with the measured data and therefore support the feasibility of these quantification methods. In conclusion, a link does exist between blood glucose energy and stress, and the highly accurate models derived for this association may serve as an adjunct tool for glycaemic control and stress management. / Thesis (Ph.D. (Electronical Engineering))--North-West University, Potchefstroom Campus, 2008.

Ziel dieser Studie war die Messung der Symphatikusaktivität als Indikator einer Stressreaktion bei handchirurgischen Eingriffen. Zwei Gruppen á 23 Patienten (Alter [Jahre] ITN 21-76(51) axPlex 27-66(52) p=0,73; BMI ITN 18,2-40,3(26,4) axPlex 20,9-34,9(25,5) p=0,97), die sich in ultraschallgesteuerter axillärer Plexusblockade (axPlex) oder Allgemeinanästhesie (ITN) einer Operation unterziehen mussten, wurden nach Genehmigung durch die Ethikkommission untersucht. Ausschlusskriterien waren ein Alter < 18 Jahre oder > 80 Jahre, eine ASA-Klassifikation > III, sowie eine Kontraindikation gegen die verwendeten Medikamente oder Narkosenformen. Die Symphatikusaktivität wurde anhand des Hautwiderstands (ESG® 1001, Ingenieurbüro Dr.Janitzki, Altenbeken, Germany) gemessen. Die Herzfrequenz (HF), der non invasive Blutdruck und die Hauttemperatur wurden erfasst. Die Messung umfasste sieben Zeitpunkte (T-Ausgangswert, T-Narkosebeginn, T-Blutsperre, T-Schnitt, T-OP-Ende, T-Aufwachraum, T-Normalstation). Die Narkosetiefe der ITN wurde mit BIS® (40-60) überwacht. Die Analyse zeigte signifikante Unterschiede zwischen beiden Gruppen. In Bezug auf die Sympathikusaktivität konnte kein Unterschied zwischen beiden Gruppen gefunden werden.