A glândula pineal de mamíferos não é uma estrutura oscilatória autônoma, exigindo a liberação de noradrenalina (Nor) na fase escura para que a melatonina seja circadianamente produzida. Na cultura padrão de glândula pineal, o órgão não expressa ritmicidade funcional e para mimetizar o padrão fisiológico de liberação de Nor, desenvolvemos a cultura temporizada com Nor. Logo, o objetivo desse trabalho foi investigar a manutenção do ritmo de expressão dos genes relógio pela cultura temporizada, e qual a via noradrenérgica envolvida. Para os estudos in vitro, realizaram-se culturas dos grupos: controle (sem Nor), agudo (cultura padrão) e temporizado (12h com Nor/12h sem Nor). Além disso, à cultura temporizada se adicionou Prasozin e/ou Propranolol. Analisou-se expressão dos genes relógio, atividade da enzima AANAT e conteúdo de melatonina no meio de cultura. No grupo temporizado, observou-se a manutenção da ritmicidade dos genes analisados, diferente do observado nos grupos controle, agudo e temporizado tratado com bloqueadores, além do aumento da atividade enzimática da AANAT e aumento do conteúdo de melatonina. Em suma, a cultura temporizada com Nor se mostra importante para evitar a arritmicidade encontrada na cultura padrão de glândula pineal. / The mammals pineal gland is not an autonomous oscillator, the circadian melatonin synthesis requires the release of norepinephrine (NE) on the dark phase. In standard pineal gland culture, the glands do not express any functional rhythmicity. To mimic the physiological pattern of NE release in the pineal gland culture, we developed a synchronized culture with NE. We aimed to investigate the maintenance of circadian clock genes expression within rat pineal gland under acute and synchronized culture and the noradrenergic pathway involved. In in vitro experiments, culture glands were under: control (without NE), acute (standard culture) and synchronized (12h with NE/12h without NE) conditions. Furthermore, in the synchronized group were added Prasozin and/or Propranolol. We investigated clock genes expression, AANAT activity and melatonin content. The synchronized culture was able to maintain the rhythmic clock genes expression, which didn´t occur in control, acute and synchronized treated with blockers groups, and was able to improve AANAT activity and melatonin synthesis. In conclusion, synchronized culture method showed as a useful approach to avoid disruption of rhythmic variations found in the standard culture.

Introdução: O choque séptico é complicação frequente e grave nos pacientes com câncer. Representa uma das principais causas de admissão em Unidade de Terapia Intensiva (UTI), com taxa de mortalidade em torno de 40% a 60%. O tratamento com vasopressor é parte fundamental do suporte hemodinâmico do paciente com choque séptico, sendo a norepinefrina o fármaco mais utilizado. Entretanto, aproximadamente 40% dos pacientes apresentam choque refratário a esse fármaco e vários eventos adversos são descritos, dentre eles vasoconstricção excessiva, redução do fluxo sanguíneo para os tecidos, distúrbios metabólicos e desequilíbrio imunológico. A vasopressina é um vasopressor não catecolaminérgico, que vem demonstrando ser eficiente vasopressor adjuvante no choque séptico. O objetivo desse estudo é avaliar se a vasopressina é superior à norepinefrina na mortalidade em 28 dias de pacientes com câncer e choque séptico. Métodos: Estudo unicêntrico, prospectivo, randomizado e duplo cego. Foram incluídos no estudo 250 pacientes com câncer e choque séptico no período de 20 de julho de 2013 a 6 de julho de 2016. Os pacientes foram randomizados para receber vasopressina (0,01 U/minuto a 0,06 U/minuto) ou norepinefrina (0,1 ug/kg/min a 1,0 ug/kg/min) como vasopressor no choque. A infusão dos fármacos foi titulada para manter a pressão arterial média (PAM) alvo ( >= 65 mmHg) após randomização. O desfecho primário foi mortalidade em 28 dias. Os desfechos secundários foram mortalidade em 90 dias, dias vivo e livres de ventilação mecânica, de vasopressores, e de terapia de substituição renal, e avaliação de disfunções orgânicas conforme o Sequential Organ Failure Assessment (SOFA) 24 horas e 96 horas após a randomização. Resultados: Foram elegíveis 1116 pacientes, sendo 250 pacientes incluídos no estudo e randomizados para vasopressina (n = 125) ou para norepinefrina (n = 125). Não houve perdas ou violação de protocolo. Não houve diferença na mortalidade em 28 dias (56,8% no grupo vasopressina vs. 52,8% no grupo norepinefrina, p = 0,525). A mortalidade em 90 dias também não foi diferente nos grupos, respectivamente nos grupos vasopressina e norepinefrina (72,0% vs. 75,2%, p = 0,566). Não houve diferença entre os grupos vasopressina e norepinefrina em relação aos dias vivos e livres de ventilação mecânica [20 (6-28) vs. 22 (7-28), p = 0,748], de dias livres de vasopressores [10 (1-23) vs. 12 (1-24), p = 0,669], e dias livres de terapia de substituição renal [20 (7- 28) vs. 21 (7-28), p = 0,819]. O escore SOFA não foi diferente entre os grupos vasopressina e norepinefrina 24 horas após a randomização [8 (5-11) vs. 7 (5-10), p = 0,425] e 96 horas após [7 (2-12) vs. 7 (3-12), p = 0,825]. Conclusão: A vasopressina não é superior à norepinefrina na mortalidade em 28 dias de pacientes com câncer e choque séptico / Background: Septic shock is a frequent complication in cancer patients. It is one of the most common admission causes in the intensive care unit (ICU), with mortality rates of 40% to 60%. Patients with septic shock often need the use of vasopressors for hemodynamic support and norepinephrine is the most used medication in this setting. However, 40% of patients have shock that is refractory to norepinephrine and lots of adverse effects are described, including excessive vasoconstriction, reduced blood flow to tissues and cells, and metabolic and immunologic disorders. Vasopressin is commonly used as an adjunct to catecholamines to support blood pressure in refractory septic shock. We hypothesized that the use of vasopressin would be more effective on the treatment of septic shock in cancer patients than norepinephrine, decreasing 28-day mortality. Methods: In this prospective and randomized, double-blind trial, we assigned patients who had cancer and septic shock to receive either vasopressin (0.01 U/minute to 0.06 U/minute) or norepinephrine (10 ?g/minute to 60 ?g/minute) in addition to open-label vasopressors. All vasopressor infusions were titrated and tapered according to protocols in order to maintain a target mean arterial pressure of 65 mmHg. The primary endpoint was 28-day mortality. Secondary outcomes included 90-day mortality, days alive and free of mechanical ventilation, free of vasopressors and renal replacement therapy, and SOFA 24 h and 96h after randomization. Results: 1116 patients were eligible to the study. 250 patients were included on the study and underwent randomization: 125 patients received vasopressin and 125, norepinephrine. There was no difference between groups in 28-day mortality (56.8% in vasopressin group vs. 52.8% in norepinephrine group, p = 0.525). In addition, 90-day mortality was not different between vasopressin and norepinephrine groups (72% vs. 75.2%, p = 0.566). There was also no difference between vasopressin and norepinephrine groups in days alive and free of mechanical ventilation [20 (6- 28) vs. 22 (7-28), p = 0.748], free of vasopressors [10 (1-23) vs. 12 (1-24), p = 0.669], and renal replacement therapy [20 (7-28) vs. 21 (7-28), p = 0.819]. SOFA score was not different between vasopressin and norepinephrine groups after 24 h [8 (5-11) vs. 7 (5-10), p = 0.425] and after 96h [7 (2-12) vs. 7 (3-12), p = 0.825]. Conclusion: Vasopressin is not superior to norepinephrine in 28-day mortality rate in cancer patients with septic shock

by Ng Ka On. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1995. / Includes bibliographical references (leaves 100-122). / Abstract --- p.i / Acknowledgement --- p.vi / Chapter 1. --- Introduction / Chapter 1.1 --- Testicular vasculature --- p.1 / Chapter 1.1.1 --- Structural organization --- p.1 / Chapter 1.1.2 --- Peculiar structural organization pertinent to the Consideration of function --- p.3 / Chapter 1.2 --- Importance of the blood flow to testicular function --- p.6 / Chapter 1.3 --- Measurement of testicular blood flow --- p.8 / Chapter 1.4 --- Control of testicular blood flow --- p.16 / Chapter 1.5 --- Adrenergic control in the testis --- p.18 / Chapter 1.5.1 --- Adrenergic innervation and source of catecholamines --- p.18 / Chapter 1.5.2 --- Regulation of testicular function --- p.20 / Chapter 1.5.3 --- Effect on testicular blood flow --- p.22 / Chapter 1.6 --- Serotonergic control in the testis --- p.23 / Chapter 1.6.1 --- Serotonergic innervation and source of serotonin --- p.23 / Chapter 1.6.2 --- Regulation of testicular function --- p.24 / Chapter 1.6.3 --- Effect on testicular blood flow --- p.25 / Chapter 1.7 --- Cholinergic control in the testis --- p.26 / Chapter 1.7.1 --- Cholinergic innervation and source of acetylcholine --- p.26 / Chapter 1.7.2 --- Regulation of testicular function --- p.28 / Chapter 1.7.3 --- Effect on testicular blood flow --- p.29 / Chapter 1.8 --- Aims of the study --- p.30 / Chapter 2. --- Materials and methods / Chapter 2.1 --- Animals --- p.31 / Chapter 2.2 --- Drugs and chemicals --- p.32 / Chapter 2.3 --- In vivo videomicroscopy method --- p.33 / Chapter 2.4 --- Hydrogen gas clearance method --- p.37 / Chapter 2.5 --- Data and statistical analyses --- p.45 / Chapter 3. --- Results / Chapter 3.1 --- Adrenergic control --- p.46 / Chapter 3.1.1 --- Response of the testicular subcapsular artery to adrenergic agonists and antagonists --- p.46 / Chapter 3.1.2 --- Effect of adrenergic agonists on testicular capillary blood flow --- p.57 / Chapter 3.2 --- Serotonergic control --- p.60 / Chapter 3.2.1 --- Response of the testicular subcapsular artery to serotonergic agonists and antagonists --- p.60 / Chapter 3.2.2 --- Effect of serotonergic agonists on testicular capillary blood flow --- p.69 / Chapter 3.3 --- Cholinergic control --- p.76 / Chapter 3.3.1 --- Response of the testicular subcapsular artery to serotonergic agonists and antagonists --- p.76 / Chapter 3.3.2 --- Effect of serotonergic agonists on testicular capillary blood flow --- p.79 / Chapter 4. --- Discussion / Chapter 4.1 --- Adrenergic control --- p.86 / Chapter 4.2 --- Serotonergic control --- p.90 / Chapter 4.3 --- Cholinergic control --- p.96 / Chapter 4.4 --- General discussion --- p.98 / Chapter 5. --- References --- p.100

by Perpetua E. Tan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1996. / Includes bibliographical references (leaves 149-157). / Abstract --- p.9 / Acknowledgments --- p.12 / List of abbreviations --- p.13 / List of Tables --- p.16 / List of Figures --- p.19 / Chapter CHAPTER 1 --- INTRODUCTION --- p.21 / Chapter CHAPTER 2 --- LITERATURE REVIEWS CATECHOLAMINES: NORADRENALINE AND ADRENALINE --- p.25 / Chapter 2.1 --- History --- p.25 / Chapter 2.2 --- Origin of plasma catecholamines --- p.25 / Chapter 2.3 --- Kinetics of entry and removal --- p.28 / Chapter 2.4 --- Levels present in plasma --- p.30 / Chapter 2.5 --- Some factors affecting plasma CA levels --- p.31 / Chapter 2.5.1 --- Effects of age --- p.31 / Chapter 2.5.2 --- Postural change --- p.32 / Chapter 2.5.3 --- Exercise --- p.32 / Chapter 2.5.4 --- Temperature change --- p.32 / Chapter 2.5.5 --- Stress --- p.33 / Chapter 2.5.6 --- Pregnancy --- p.34 / Chapter 2.5.7 --- Disease --- p.35 / Chapter 2.6 --- Actions in the body --- p.35 / Chapter 2.6.1 --- Plasma endogenous catecholamines --- p.35 / Chapter 2.6.2 --- Plasma exogenous catecholamines and medicine --- p.36 / Chapter 2.6.2.1 --- Clinical uses --- p.36 / Chapter 2.6.2.2 --- Effects --- p.37 / Chapter 2.6.2.3 --- Side effects --- p.38 / Chapter 2.7 --- Binding of catecholamines in plasma --- p.38 / Chapter 2.8 --- Measurement of catecholamines in plasma --- p.38 / Chapter 2.8.1 --- Chemistry --- p.38 / Chapter 2.8.2 --- Extraction and purification --- p.39 / Chapter 2.8.3 --- Biological methods --- p.40 / Chapter 2.8.4 --- Colorimetry --- p.41 / Chapter 2.8.5 --- Radioimmunoassay and radioenzymatic assay --- p.41 / Chapter 2.8.6 --- Enzyme-linked immunoassay --- p.42 / Chapter 2.8.7 --- Gas chromatography --- p.42 / Chapter 2.8.8 --- Liquid chromatography --- p.42 / Chapter 2.8.8.1 --- Fluorometry --- p.43 / Chapter 2.8.8.2 --- Electrochemical detection --- p.43 / Chapter 2.9 --- Plasma protein binding of basic drugs --- p.44 / Chapter 2.9.1 --- Binding to albumin --- p.45 / Chapter 2.9.2 --- Binding to alpha-1-acid-glycoprotein --- p.45 / Chapter 2.9.3 --- Binding to other proteins --- p.45 / Chapter 2.9.4 --- Factors affecting drug binding --- p.46 / Chapter 2.9.4.1 --- Pregnancy --- p.46 / Chapter 2.9.4.2 --- Age --- p.46 / Chapter 2.9.4.3 --- Disease states --- p.46 / Chapter 2.9.5 --- Separation procedures to reveal and follow drug protein binding --- p.47 / Chapter 2.9.5.1 --- Equilibrium dialysis --- p.47 / Chapter 2.9.5.2 --- Ultrafiltration --- p.48 / Chapter 2.9.5.3 --- Ultracentrifugation --- p.48 / Chapter 2.9.5.4 --- Gel Filtration --- p.48 / Chapter CHAPTER 3 --- ANALYTICAL TECHNIQUE : PLASMA CATECHOLAMINE ANALYSIS --- p.49 / Chapter 3.1 --- HPLC determination with coulometric detection of catecholamines --- p.49 / Chapter 3.1.1 --- Introduction --- p.49 / Chapter 3.1.2 --- Basic equipment --- p.49 / Chapter 3.1.3 --- Mobile phase preparation --- p.50 / Chapter 3.1.3.1 --- Reagent A (Citrate-acetate-EDTA buffer) --- p.50 / Chapter 3.1.3.2 --- Reagent B (ion pairing reagent) --- p.50 / Chapter 3.1.3.3 --- Mobile phase mixture --- p.50 / Chapter 3.1.4 --- Detector settings --- p.51 / Chapter 3.1.5 --- Sample collection and storage --- p.51 / Chapter 3.2 --- Reagents and solutions --- p.52 / Chapter 3.2.1 --- Acid-washed alumina --- p.52 / Chapter 3.2.2 --- Tris buffer solution --- p.53 / Chapter 3.2.3 --- Washing solution --- p.53 / Chapter 3.2.4 --- Acetic acid solution --- p.53 / Chapter 3.2.5 --- EDTA-HC1 solution --- p.53 / Chapter 3.2.6 --- Citric acid solution --- p.53 / Chapter 3.2.7 --- Stock solutions --- p.54 / Chapter 3.2.7.1 --- Catecholamine standards --- p.54 / Chapter 3.2.7.2 --- Dihydroxybenzylamine (Internal) standard --- p.54 / Chapter 3.2.8 --- Stripped fresh frozen plasma --- p.54 / Chapter 3.2.9 --- Sorensen's phosphate buffer containing 0.6% NaCl --- p.55 / Chapter 3.2.10 --- Control standards --- p.55 / Chapter 3.3 --- Voltammogram of catecholamines and internal standard used --- p.55 / Chapter 3.4 --- Maintenance of the HPLC-Coulometric detector system --- p.56 / Chapter 3.5 --- Optimization of the extraction method --- p.58 / Chapter 3.5.1 --- Amount of alumina for adsorption of CA --- p.58 / Chapter 3.5.2 --- pH of tris buffer for maximum uptake of CA onto alumina --- p.58 / Chapter 3.5.3 --- Optimum time for maximum uptake of CA onto alumina --- p.59 / Chapter 3.5.4 --- Optimum time for maximum desorption of CA into acid solution --- p.59 / Chapter 3.5.5 --- Optimum volume of acid solution for maximum desorption of CA --- p.60 / Chapter 3.6 --- Validation of the method --- p.60 / Chapter 3.6.1 --- Linearity --- p.60 / Chapter 3.6.2 --- Recovery --- p.61 / Chapter 3.6.3 --- Reproducibility --- p.62 / Chapter 3.6.4 --- Stability --- p.62 / Chapter 3.7 --- Results --- p.63 / Chapter 3.8 --- Discussion --- p.79 / Chapter CHAPTER 4 --- CLINICAL APPLICATIONS OF THE CATECHOLAMINE ASSAY --- p.84 / Chapter 4.1 --- Introduction --- p.84 / Chapter 4.1.1 --- Applications of catecholamines assay in clinical science --- p.84 / Chapter 4.2 --- : PLASMA CATECHOLAMINES AFTER INDUCTION OF ANAESTHESIA AT CAESARIAN SECTION --- p.84 / Chapter 4.2.1 --- Introduction --- p.84 / Chapter 4.2.2 --- Patients and methods --- p.86 / Chapter 4.2.3 --- Blood sampling and storage --- p.87 / Chapter 4.2.4 --- Statistics used --- p.87 / Chapter 4.2.5 --- Results --- p.88 / Chapter 4.2.6 --- Discussion --- p.99 / Chapter 4.3 --- EPINEPHRINE INFILTRATION IN SINUS SURGERY --- p.101 / Chapter 4.3.1 --- Introduction --- p.101 / Chapter 4.3.2 --- Patients and methods --- p.102 / Chapter 4.3.3 --- Blood sampling and storage --- p.103 / Chapter 4.3.4 --- Results --- p.104 / Chapter 4.3.5 --- Discussion --- p.108 / Chapter CHAPTER 5 --- ANALYTICAL TECHNIQUE: PLASMA PROTEIN BINDING OF CATECHOLAMINES --- p.110 / Chapter 5.1 --- Equilibrium dialysis for protein binding of drugs --- p.110 / Chapter 5.1.1 --- Introduction --- p.110 / Chapter 5.1.2 --- Dialyzing apparatus --- p.110 / Chapter 5.1.3 --- Sample collection and storage --- p.111 / Chapter 5.1.4 --- Reagents and solutions --- p.111 / Chapter 5.1.4.1 --- Ascorbic acid --- p.111 / Chapter 5.1.4.2 --- Glutathione --- p.111 / Chapter 5.1.4.3 --- Sodium metabisulfite --- p.111 / Chapter 5.1.4.4 --- Dialysis buffer --- p.111 / Chapter 5.1.5 --- Dialysis membrane --- p.112 / Chapter 5.1.6 --- Equilibrium dialysis --- p.112 / Chapter 5.2 --- Optimization of the binding parameters --- p.113 / Chapter 5.2.1 --- Types of preservatives for stability of catecholamines during dialysis --- p.113 / Chapter 5.2.2 --- Dialysis buffer --- p.114 / Chapter 5.2.3 --- Dialysis time and volume of sample --- p.114 / Chapter 5.2.4 --- Dialysis membrane --- p.115 / Chapter 5.2.5 --- Catecholamines concentration for dialysis --- p.114 / Chapter 5.3 --- Total protein analysis- Lowry Method --- p.115 / Chapter 5.3.1 --- Reagents and solutions --- p.116 / Chapter 5.3.1.1 --- Reagent A (Alkaline copper reagent) --- p.116 / Chapter 5.3.1.2 --- Reagent B (Folin-Ciocalteus phenol reagent with water) --- p.116 / Chapter 5.3.2 --- Stock standard and controls --- p.116 / Chapter 5.3.2.1 --- Human serum albumin standard --- p.116 / Chapter 5.3.2.2 --- Controls --- p.116 / Chapter 5.3.3 --- Procedure --- p.116 / Chapter 5.4 --- Results --- p.117 / Chapter 5.5 --- Discussion --- p.126 / Chapter CHAPTER 6 --- CONCLUSIONS --- p.130 / APPENDIX --- p.134 / CHEMICALS AND REAGENTS --- p.146 / REFERENCES --- p.149

Emotional events are often better preserved in memory than events without an emotional component. Emotional stimuli benefit from capturing and holding the attention of a perceiver to a higher degree than more emotion-neutral stimuli. Arousal associated with experiencing emotionally valenced stimuli or situations affects every major stage in creating, maintaining and retrieving lasting memories. Presented in this thesis were models delineating the behavioral and neurological mechanisms that might explain arousal-induced effects on subsequent memory outcome. Based on a study of relevant literature, findings were presented in this thesis that highlight amygdala activation as crucial for the enhancement of memory generally associated with emotional arousal. The amygdala modulates processing in other areas of the brain involved in memory. Heightened levels of norepinephrine, stemming from sympathetic nervous system activation, underlies observable arousal-induced memory effects and seem to be a crucial component in enabling glucocorticoid augmentation of memory. Arousal seems to further amplify the biased competition between stimuli that favors the neural representation of motivationally relevant stimuli and stimuli of a sensory salient nature. The aim of this thesis was to outline the impact of emotional arousal on different stages of memory processing, including processes for memory formation, strengthening of memory traces, and eventual subsequent retrieval.

The stress response is an evolutionarily conserved mechanism critical for survival that requires orchestration of different systems in the body. Corticotropin-releasing hormone (CRH) neurons of the hypothalamic paraventricular nucleus (PVN) represent the final common pathway leading to HPA axis activation in response to stress. Noradrenergic inputs to CRH neurons in the PVN provide a powerful drive to activate the HPA axis. Previous anatomical studies have shown that noradrenergic afferents synapse directly on CRH neurons, but electrophysiological analyses indicate that the noradrenergic activation of CRH neurons is mediated primarily by the stimulation of presynaptic glutamatergic neurons. Here, using whole cell patch clamp recordings in identified CRH neurons, I demonstrate that norepinephrine (NE) stimulates excitatory synaptic inputs by activating postsynaptic α1 adrenergic receptors in CRH neurons and inducing the release of the retrograde messenger nitric oxide, which drives upstream glutamate neurons to elicit spike-dependent synaptic glutamate release onto the CRH neurons. Notably, the NE effect is dependent on ATP transmission and astrocytic function, suggesting that astrocytes serve as an intermediary in the retrograde activation of glutamateregic synaptic inputs to the CRH neurons. In addition, I also show that the NE-induced excitation of CRH neurons is stress-status sensitive and corticosterone dependent, in that stress-induced corticosterone causes internalization of membrane α1 adrenergic receptors to desensitize the CRH neurons to NE. Taken together, my findings provide evidence that NE excites CRH neurons in a stress state-dependent manner by a retrograde NO stimulation of local glutamate circuits that is dependent on glial activation. This retrograde trans-neuronal-glial regulation of excitatory synaptic inputs to CRH neurons by NE provides a mechanism for the NE activation of the HPA axis in the early stage of stress response. The stress-/corticosterone-induced desensitization of CRH neurons to NE modulation by the internalization of α1 adrenergic receptors confers a stress state-dependent resistance of the CRH neurons to repeated noradrenergic activation, which provides a mechanism for the negative feedback regulation of the CRH neurons and the HPA axis by stress and glucocorticoids, and a means to restore neuroendocrine homeostasis after stress exposure. / acase@tulane.edu

Low-load repetitive work (LLRW) and mental load are important risk factors for the development of workrelated muscle pain. The link between these risk factors and the development of pain is still not understood, but stimulation of chemo-sensitive receptors in the muscle probably plays an important role. It has been suggested that sensitising substances may accumulate in the muscle during LLRW, especially when combined with mental load. The overall purpose of this thesis was to try to shed some light on the effects of LLRW on the concentration of sensitising substances (glutamate, prostaglandin E2 (PGE2), norepinephrine (NE)) and on metabolism (lactate, pyruvate and oxygenation) in the trapezius muscle of healthy controls (CON) and subjects with trapezius myalgia (TM). A first step was to investigate whether females with TM exhibit higher absolute concentrations of glutamate and PGE2 in the affected muscle during rest. Using Microdialysis (MD) females with TM and asymptomatic controls were studied during four hours of rest. [Glutamate] and [PGE2] during rest did not differ between groups. A second step was to investigate, in a simulated occupational setting, the effects of LLRW on the concentration of sensitising substances and metabolism in the trapezius muscle of TM and CON, and whether increased work duration resulted in a progressive effect. Asymptomatic females were studied during baseline rest, 30 versus 60 min work and recovery, using MD and near infrared spectroscopy (NIRS). Subjects with TM were studied during baseline rest, 30 min work and recovery. [Glutamate] and [lactate] increased in response to work, but not progressively with increased work duration. [Glutamate] was at all time points significantly lower in TM. [PGE2]and oxygenation remained unchanged during work for CON, while for TM oxygenation decreased significantly during work. In TM [pyruvate] increased during both work and recovery, and a significant interaction between groups was found for [pyruvate] during recovery; while moderately increased in CON it increased progressively in TM. The effects of LLRW with and without superimposed mental load on intramuscular [NE], muscle activity and oxygen saturation in the trapezius were also investigated and compared. Using MD, electromyography and NIRS, healthy females were studied on two occasions; during 30 min LLRW and during 30 min LLRW with superimposed mental load. During work [NE], and muscle activity, were increased, while oxygenation decreased, but no differences between occasions. However, recovery of [NE] to baseline was slower after LLRW with superimposed mental load. The findings of the present thesis suggest: (i) no inflammation, or increased interstitial [glutamate] in TM; (ii) LLRW causes an increased anaerobic metabolism in both TM and CON; (iii) no effect of work duration was found; (iv) a significant difference in the effects of LLRW on the interstitial milieu of the trapezius muscle in TM as compared to CON; (v) LLRW causes a significant increase in [NE], but superimposed mental load does not cause a further increase; (vi) LLRW with a superimposed mental load may result in a slower recovery to baseline [NE] as compared with LLRW alone.

Electroconvulsive therapy (ECT) effectively treats depression by administration of repeated seizure-inducing electrical stimuli. Sprague-Dawley rats were administered 6 electroconvulsive shocks (ECS) over 2 weeks, and in vivo single unit extracellular electrophysiological activity was recorded after 48 hours. Overall firing activity in the locus coeruleus and ventral tegmental area was unchanged, suggesting the therapeutic efficacy of ECT may not be attributed to increased norepinephrine and dopamine release. There were more spontaneously active neurons in the substantia nigra pars compacta (SNc), indicating greater dopamine tone in the nigrostriatal motor pathway, which may contribute to alleviation of psychomotor retardation. In the facial motor nucleus (FMN), locally administered norepinephrine, but not serotonin, facilitated greater glutamate-induced firing, which may contribute to improved facial motricity. Current results indicate that repeated ECS enhances postsynaptic norepinephrine neurotransmission in the FMN and SNc dopamine neurotransmission, which could represent the mechanism behind the alleviation of depressive symptoms including psychomotor retardation.

Neurons in the Locus coeruleus (LC) play an important role in the central CO2 chemosensitivity. However, the molecular mechanisms for neuronal CO2 chemosensitivity remain unclear. To demonstrate the expression of pH/CO2 sensitive ion channels, we screened the inward rectifier K+ channels (Kir) and transient receptor protein (TRP) channels, as parallel studies in this lab suggested that certain Kir and TRP channels are involved in neuronal responses to high levels of CO2. Our results showed that several members of the Kir and TRP channel families were robustly expressed in the LC neurons at the mRNA level. Of particular interest are TRPC5, Kir4.1 and Kir5.1 channels that are all pH-sensitive. The rich expression of various pH-sensitive Kir and TRP channels suggests that these ion channels are likely to play a role in the chemosensitivity of LC neurons.

Electroconvulsive therapy (ECT) effectively treats depression by administration of repeated seizure-inducing electrical stimuli. Sprague-Dawley rats were administered 6 electroconvulsive shocks (ECS) over 2 weeks, and in vivo single unit extracellular electrophysiological activity was recorded after 48 hours. Overall firing activity in the locus coeruleus and ventral tegmental area was unchanged, suggesting the therapeutic efficacy of ECT may not be attributed to increased norepinephrine and dopamine release. There were more spontaneously active neurons in the substantia nigra pars compacta (SNc), indicating greater dopamine tone in the nigrostriatal motor pathway, which may contribute to alleviation of psychomotor retardation. In the facial motor nucleus (FMN), locally administered norepinephrine, but not serotonin, facilitated greater glutamate-induced firing, which may contribute to improved facial motricity. Current results indicate that repeated ECS enhances postsynaptic norepinephrine neurotransmission in the FMN and SNc dopamine neurotransmission, which could represent the mechanism behind the alleviation of depressive symptoms including psychomotor retardation.