Submitted by Celso Magalhaes (celsomagalhaes@ufrrj.br) on 2018-09-12T18:08:44Z No. of bitstreams: 1 2017 - Julia Dias Villas Boas.pdf: 1378660 bytes, checksum: 2a1537e1b92056b0327c8e50b73feb34 (MD5) / Made available in DSpace on 2018-09-12T18:08:44Z (GMT). No. of bitstreams: 1 2017 - Julia Dias Villas Boas.pdf: 1378660 bytes, checksum: 2a1537e1b92056b0327c8e50b73feb34 (MD5) Previous issue date: 2017-04-28 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico - CNPq / The horse has a natural predisposition for the sport, however, its use in competitions can result in stress related problems that impair its sporting performance and especially its health. In this way it is fundamental not only to understand how the different risk and resilience factors to different stressors influence the response to stress, but also to develop strategies that can prevent or minimize the deleterious effects of stress. In this sense, acupuncture is an ancient technique of Traditional Chinese Medicine that has been used in the treatment and prevention of stress-related diseases. The present study proposed the use of two models of stress: one physical (physical exercise) and another psychological (startle model) to verify the reactivity to the stress of athletes horses. In addition, it was also evaluated if horses of different sporting modalities present different psychological stress responses and if acupuncture can alter the responses to physical stress. In the experiment 1, 16 Thoroughbred race horses were submitted to a exercise in the field of high intensity and short duration (12 m / s, 4 min). The RR intervals for analysis of the Heart Rate Variability were acquired through the Polar Equine ? heart rate monitor and blood samples were collected before and immediately after 2h, 4h, 6h, and 24h after exercise. The exercise promoted autonomic alterations in the sympatho-vagal balance since it significantly increased the low frequency component (LF), the heart rate and the LF / HF ratio, and decreased the high frequency component (HF) (p <0.01). There was an increase in hematocrit, plasma proteins, glucose and plasma lactate immediately after exercise (p <0.001). There was an increase (p <0.01) in serum cortisol values after 30 minutes, returning to baseline values after 60 min. However, no significant difference was observed in plasma cytokines IL-1? and IL-6 between moments after exercise and baseline. In experiment 2, horses of the experimental group 1 after exercise were randomly divided into two groups: CTL (C2): Control (without manipulation) and ACUP (C2)): animals submitted to weekly sessions of acupuncture at points VG1, C7, VG20 and B52 for 10 weeks. After the treatment period the animals repeated the same exercise and the same parameters were analyzed. Acupuncture reduced the LF / HF ratio, promoting a faster recovery of the animals, showing no influence on the other parameters analyzed. In the experiment 3, 24 equines were used, from three equestrian modes: Polo (PSI) (n = 9), Dressage (Brazilian Horse Riding) (n = 6) and Endurance (n=6) were subjected to the experimental model of startling through the abrupt opening of an umbrella. The results showed that endurance horses presented a significantly less intense startle-induced autonomic response than Polo and Dressage horses (lower LF / HF ratio at the time of the jump), paradoxically Enduro horses have cortisol levels in response in response to the startle than Polo horses. However, there was no difference between the modalities in the behavioral response after the startle, and Polo horses had significantly higher baseline levels of cortisol than the other modalities and did not change their cortisol levels in response to stress. Thus, we can conclude that 1) the exercise in the field of high intensity and short duration promoted adaptive changes characteristic of stress, being able to be used in studies of reactivity to stress in race horses; 2) acupuncture has a modulating effect on the stress-induced autonomic response in athletic horses, and 3) the equestrian modalities of Dressage, Polo and Endurance present different stress reactivity / O cavalo tem uma predisposi??o natural para o esporte, no entanto, o seu uso em competi??es pode resultar em problemas relacionados ao estresse que prejudicam seu desempenho esportivo e principalmente a sua sa?de. Desta forma ? fundamental n?o apenas entender como os diferentes fatores de risco e de resili?ncia a diferentes estressores influenciam a resposta ao estresse, como tamb?m desenvolver estrat?gias que possam prevenir ou minimizar os efeitos delet?rios do estresse. Neste sentido a acupuntura ? uma t?cnica milenar da Medicina Tradicional Chinesa que tem sido utilizada no tratamento e preven??es de doen?as relacionadas ao estresse. O presente estudo prop?s o uso de dois modelos de estresse: um f?sico (exerc?cio f?sico) e outro psicol?gico (modelo de sobressalto) para verificar a reatividade ao estresse de cavalos atletas. Al?m disso, tamb?m foi avaliado se cavalos de diferentes modalidades esportivas apresentam respostas ao estresse de psicol?gico distintas e se acupuntura pode alterar as respostas ao estresse f?sico. No experimento 1, 16 equinos de corrida da ra?a Puro Sangue Ingl?s foram submetidos ao exerc?cio a campo de alta intensidade e curta dura??o (12 m/s, 4min). Os intervalos RR para an?lise da Variabilidade da Frequencia Card?aca foram adquiridos atrav?s do frequenc?metro card?aco Polar Equine? e as amostras de sangue foram coletadas antes e, imediatamente, 2h, 4h, 6h, e 24h ap?s o exerc?cio. O exerc?cio promoveu altera??es auton?micas no balan?o simpato-vagal uma vez que aumentou significativamente o componente de baixa frequ?ncia (LF), a frequ?ncia card?aca e a raz?o LF/HF e diminuiu o componente de alta frequ?ncia (HF) (p < 0.01). Houve aumento do hemat?crito, das prote?nas plasm?ticas, glicose e lactato plasm?tico imediatamente ap?s o exerc?cio (p < 0.001). Houve aumento (p<0.01) nos valores s?ricos de cortisol ap?s 30 minutos, retornando aos valores basais ap?s 60min. No entanto, n?o foi observado diferen?a significativa nas citocinas plasm?ticas IL-1? e IL-6 entre os momentos ap?s exerc?cio e o momento basal. No experimento 2: os equinos do experimento 1 ap?s o exerc?cio foram aleatoriamente divididos em dois grupos: CTL (C2): Controle (sem manipula??o) e ACUP (C2)ACUP (C2): animais submetidos a sess?es semanais de acupuntura nos pontos VG1, C7, VG20 e B52 durante 10 semanas. Ap?s o per?odo de tratamento os animais repetiram o mesmo exerc?cio e foram analisados os mesmos par?metros. A acupuntura reduziu a raz?o LF/HF, promovendo uma recupera??o mais r?pida dos animais n?o apresentando influ?ncia nos demais par?metros analisados. No experimento 3, foram utilizados 24 equinos, pertencentes a tr?s modalidades equetres: P?lo (ra?a PSI) (n=9), Adestramento (ra?a Brasileiro de Hipismo) (n=6) e Enduro (Puro Sangue ?rabe) (n=9) submetidos ao modelo experimental de sobressalto atrav?s da abertura abrupta de um guarda-chuva. Os resultados mostraram que cavalos de enduro apresentaram resposta auton?mica induzida pelo sobressalto significativamente menos intensa que cavalos de Polo e Adestramento (menor raz?o LF/HF no momento do sobressalto), paradoxalmente cavalos de Enduro possuem n?veis de cortisol em resposta ao sobressalto mais altos que cavalos de Polo. N?o houve diferen?a entre as modalidades na resposta comportamental ap?s o sobressalto, no entanto cavalos de P?lo apresentam n?veis basais de cortisol significativamente mais altos que as demais modalidades e n?o variaram seus n?veis de cortisol em resposta ao estresse. Dessa forma, podemos concluir que 1) o exerc?cio a campo de alta intensidade e curta dura??o promoveu altera??es adaptativas caracter?stica de estresse, podendo ser utilizado em estudos de reatividade ao estresse em cavalos de corrida; 2) a acupuntura tem um efeito modulador da resposta auton?mica induzida pelo estresse em cavalos atletas e 3) as modalidades equestres de Adestramento, Polo e enduro apresentam reatividade ao estresse distintas

The aim of this thesis was to validate the use of infrared thermography (IRT) to non-invasively measure stress and/or pain in cattle. The main approach was to measure changes in heat emitted from superficial capillaries around the eye (referred to as eye temperature) in response to various aversive husbandry procedures used routinely on farms. In addition, various exogenous challenges were given to investigate the role of the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS) in regulating the eye temperature response. No evidence was found to support the hypothesis that an increase in eye temperature was due to HPA activity in cattle. A rapid drop in eye temperature occurred immediately after disbudding, an electric prod, startling and shouting. It is suggested that this was caused by the redirection of blood from the capillary beds via sympathetically-mediated vasoconstriction. Therefore, the role of the ANS was tested by measuring eye temperature, heart rate variability (HRV) and plasma catecholamine responses simultaneously. Somatic pain from disbudding and initial responses to surgical castration included a synchronised drop in eye temperature, increases in catecholamines and changes in HRV indicative of increased sympathetic activity. The role of the sympathetic nervous system was further confirmed by a drop in eye temperature that occurred following an epinephrine challenge. In contrast, deeper visceral pain from castration caused a more marked increase in eye temperature and changes in HRV indicative of increased parasympathetic tone. The underlying mechanism driving the increase in eye temperature is unknown; however, it is possible that it may be caused by vasodilation due to increased parasympathetic activity. These differences in ANS responses to different procedures, detected by IRT and HRV, may be due to the nature of the pain and the relative fear associated with the procedure. In summary, this research showed that during stress or pain, the heat emitted from superficial capillaries around the eye changes as blood flow is regulated under ANS control and these changes can be quantified using IRT. A combination of IRT and HRV is a non-invasive way to measure ANS activity and assess acute welfare impacts of husbandry practices in cattle. Further research using pharmacological inhibition and stimulation of the ANS activity would be beneficial to fully understand the underlying regulatory mechanisms of the eye temperature and HRV responses in cattle and other species during stress and/or pain. The full capability of IRT and HRV for detection of disease and emotional states and the effects of different intensities of pain, individual traits and previous experience also deserve attention.

研究目的 失眠的過度激發假說是目前最廣為接受的失眠病因之一，失眠者通常可觀察到具有身心過度激發的狀態，其中認知神經過度激發假說更由中樞神經的角度探討失眠者的過度激發現象，且已有許多證據支持此觀點。然而過度激發因素在失眠病程上的影響仍不明確，不論在前置因子或是持續因子的層面，激發因素皆經常被提及與討論。本研究以未失眠但具有高睡眠脆弱特質之族群作為研究對象，企圖模擬失眠者在失眠初發之前的狀態，另加入睡前及早晨的自主神經系統與主觀激發狀態之測量，比較其與低睡眠脆弱特質組在有無壓力誘發狀態下，兩組的睡眠中訊息處理程度、睡前及早晨的自主神經系統激發程度與主觀激發狀態，藉以了解（1）壓力是否會引發個體進入較高的主、客觀激發狀態；(2)睡眠脆弱特質在不同的激發程度下，是否會對於個體的睡前、睡眠中及早晨的激發程度造成影響，以初步推論激發狀態因素在失眠病程中所扮演之角色。 方法 以壓力下失眠反應量表（Ford Insomnia Response to Stress Test, FIRST）區分出高睡眠脆弱特質組（HV）13位（6男、7女）、低睡眠脆弱特質組（LV）14位（6男、8女），年齡為19-32歲之健康成人。每位受試者均需在睡眠實驗室進行3個夜晚之夜間睡眠記錄，包含第一晚的PSG測量以排除個案有其他睡眠疾患，並讓受試者習慣實驗環境；第二晚及第三晚則交互平衡操弄基礎情境或壓力情境，在壓力情境下，受試者被告知將進行即席演講，需在睡前抽出演講題目，並於隔天早晨喚醒後10分鐘內發表一篇內容充實、呼應主題之演說，隨後測量心跳變異率（heart rate variability，HRV）、平均心跳間距（r-r interval，RRI）、主觀身心激發狀態（Pre sleep arousal scale，PSAS）等主客觀激發程度，入睡後進行整夜的ERP（事件相關電位[Event-related potential，ERP]）測量，誘發ERPs之實驗流程以oddball典範為主，並於早晨起床後再次進行HRV、RRI及PSAS之測量。 結果 以2（組別）x 2（情境）之混和設計二因子變異數分析比較各組在不同情境下的主客觀激發程度指標是否有所不同。結果顯示壓力確實能引發受試者進入較高的主客觀激發狀態，包含睡前及早晨有較快的平均心跳速率、較高的主觀身心激發程度，而在NREM睡眠中可發現HV在有壓力的情境下，對外界的訊息處理程度顯著較LV組增加，包含較快的N1與較慢的N350出現，但HV在壓力下亦有較快的P2與較強的P900，顯示對外界訊息的抑制功能上升，且隨著睡眠更深，進入慢波睡眠時，P2及P900亦顯著較LV強，表現出更多的抑制外界訊息能力。 結論 本研究探討睡眠脆弱特質在不同激發狀態下對於睡眠的影響，結果顯示壓力能引發個體較高的激發狀態，然而在未失眠族群中，高睡眠脆弱特質對於認知激發狀態下的睡眠中訊息處理程度雖有提高，但可發現高睡眠脆弱特質組亦有較高的抑制外界訊息能力，而不致於使得激發狀態過度影響其睡眠，此結果部分支持失眠的認知神經過度激發假說，過度激發因素可能在持續因子的部分影響性較大，造成個體產生對睡眠的抱怨。另一方面，本研究結果亦彰顯失眠的高危險群的及早介入預防之重要性。 / Introduction: Conditioned hyperarousal has been theorized to be a major etiological factor in chronic insomnia patients. It has been suggested that insomniacs showed more arousal than non-insomniacs in many psychological and physiological measures, including enhanced information processing during sleep as measured by NREM ERPs. However, the role of hyperarousal on the course of development of insomnia remained unclear, it has been considered as a predisposing trait and/or perpetuating factor in the cause of insomnia. The present study compared arousal levels around sleep onset, during sleep and in the morning between non-insomniac individuals with low and high vulnerability to stress-related sleep disturbance, as high vulnerable individuals were proposed to be predisposed to chronic insomnia. The objectives of the study are therefore to investigate: 1) the effect of an acute stressor on arousal level prior, after, and during sleep, and 2) the differences in stress reactivity between individual with high and low vulnerability to stress-related sleep disturbances. Method: Fourteen healthy individuals scoring low (LV) and thirteen healthy individuals scoring high (HV) on the Ford Insomnia Response to Stress Test (FIRST) were studied. All subjects had to sleep in the lab for three nights: a screening/ adaptation night, then a baseline night and a stress night. The sequences of the later two nights were counterbalanced across subjects. During the stress night, subjects were informed that they would be required to give a speech immediately after waking up. Heart rate variability (HRV), r-r interval (RRI) of EKG and subjective arousal level (Pre sleep arousal scale, [PSAS]) was accessed before lights off and in the morning. Then sleep ERP was recorded during the night. An odd-ball paradigm was conducted to evoke ERPs throughout the night. Result: Mixed two-way ANOVAs were used to compare the differences between vulnerabilities and conditions. Both HV ans LV showed higher subjective arousal level and smaller RRI under the stress condition than the baseline condition. During NREM sleep, HV showed increased information processing under stress condition than LV as shown by faster N1, slower N350. Also, HV showed increased inhibition under stress condition than LV, with faster P2 and higher P900. Stronger P2 and P900 were also observed in HV when reached slow-wave sleep stage, comparing to LV. Conclusion: Both groups showed more arousal under stress condition than baseline condition, indicating an acute stress can lead to a higher arousal level. Moreover, high vulnerable individuals showed increased information processing during NREM sleep than low vulnerable individuals, but also showed more inhibition to prevent sleep from being disturbed by external stimulus. The results suggest that increased information processing in reacting to stress may be a predisposing trait for sleep disturbances. However, sleep may be protected by a compensatory inhibitory process in those who have not developed a long-term insomnia.

<p>Anemia is common in patients with chronic kidney disease (CDK), contributes to reduced Quality of Life (QoL) and is associated with cardiovascular disease, morbidity and mortality. Epoetin raises hemoglobin (Hb) and increases QoL and physical exercise capacity. Because of concerns about safety and economics, current anemia treatment with epoetin aims to achieve subnormal Hb (110-120 g/l). Normalization of Hb may be of additional benefit regarding QoL and cardiovascular effects. The present study examines the effects of Hb normalization with epoetin on safety variables, QoL, graft function after kidney transplantation, dialysis adequacy, hemorheology, hemodynamics and cardiac autonomic function in CKD patients. </p><p>In a randomized, multicenter study comprising 416 pre-dialysis and dialysis patients no difference was observed between patients treated to a normal or a subnormal Hb level on mortality, thrombovascular events, serious adverse events, vascular access thrombosis and residual renal function. QoL was enhanced in a subgroup of hemodialysis patients. Pretransplant epoetin treatment directed toward normal Hb levels did not result in worse graft function during 6 postoperative months. Dialysis adequacy was reduced in a subgroup of hemodialysis patients after normalization of Hb. The blood flow properties of pre-dialysis patients were altered. The hemorheological investigation demonstrated that Hb normalization caused a parallel increase in hematocrit and blood viscosity without other hemorheological changes. While the total peripheral resistance index increased, the cardiac index (CI) decreased. In a separate study cardiac autonomic function, measured by heart rate variability, was decreased in pre-dialysis patients. It was improved, but not fully normalized, by Hb normalization. </p><p>On the basis of this study, Hb normalization with epoetin appears to be safe and increases QoL in hemodialysis patients though may result in lower dialysis adequacy and increased blood pressure. A reduction in CI and improved cardiac autonomic function indicate a positive effect on cardiovascular function.</p>

Sleep is a basic need as important as physical fitness and good nutrition. Without enough sleep, we will create a sleep debt and experience sleepiness. Sleepiness can be defined as the inability to stay awake, a condition that has become a health problem in our 24-hour-7-day-a-week society. Estimates suggest that up to one-third of the population suffers from excessive sleepiness. Among other interactions, sleepiness affects our performance, increasing the risk of being involved in accidents. A considerable portion of work related accidents and injuries are related to sleepiness resulting in large costs for the individuals and society. Professional drivers are one example of workers who are at risk of sleepiness related accidents. Up to 40% of heavy truck accidents could be related to sleepiness. A better knowledge about reliable indicators and predictors of sleepiness is important in preventing sleepiness related accidents. This thesis investigates both objective and subjective indicators of sleepiness, how these relate to each other, and how their pattern changes over time. The indicators investigated were electroencephalography, heart rate variability, simple reaction time, head movement, and subjective ratings of sleepiness (Study I-IV). In Study V, a questionnaire study was conducted with professional drivers in northern Sweden. This study mainly deals with predictors of sleepiness. When subjects were sleep deprived both objective and subjective ratings indicated a rapid increase in sleepiness during the first hour of the test followed by a levelling off. This change in pattern was evident for all the indicators except heart rate and heart rate variability. On the other hand, HRV was correlated with the increase of EEG parameters during the post-test sleep period. The changes in pattern of the indicators included in the thesis are analysed in the perspective of temporal patterns and relationships. Of the tested indicators, a subjective rating of sleepiness with CR-10 was considered to be the most reliable indicator of sleepiness. Of the investigated predictors of sleepiness, prior sleep habits were found to be strongly associated to sleepiness and the sleepiness related symptoms while driving. The influences of driving conditions and individual characteristics on sleepiness while driving were lower. A multidisciplinary approach when investigating and implementing indicators and predictors of sleepiness is important. In addition to their actual relations to the development of sleepiness, factors such as technical and practical limitations, work, and individual and situational needs must be taken into account.

There is a significant comorbidity between anxiety/depression and functional gastrointestinal syndromes, such as irritable bowel syndrome (IBS) and functional dyspepsia. The pathophysiological link between emotions and the gut is not known. A model of an emotional motor system (EMS) which reacts to interoceptive and exteroceptive stress has been proposed. EMS consists of specific brain structures including anterior cingulate cortex (ACC), amygdala, hippocampus and hypothalamus and mediates their communication to the rest of the body (including the gastrointestinal tract) through the hypothalamus-pituitary-adrenal (HPA) axis, the autonomic nervous system (ANS) and by a pain modulation system. The aim of this thesis was to test the EMS model by studying the relationship between symptoms of anxiety and depression and IBS-like symptoms in patients with recurrent unipolar depression, in patients with IBS and in a sample of a normal Swedish population. The peripheral limb of EMS (ANS, HPA axis and the pain modulations system) was tested in patients with IBS and control subjects. Spectral heart rate variability was used to investigate ANS function in patients with refractory IBS and in healthy controls. The HPA axis function was tested by a weight adjusted low dose dexamethasone suppression test in control subjects. The influence of catecholamine degradation on pain modulation was tested by analyzing val158met catechol-o-methyl transferase (COMT) polymorphism in patients with IBS and in control subjects. We found a significant relationship between symptoms of anxiety/depression and IBS-like symptoms in patients with recurrent unipolar depression, in patients with IBS and in a sample of the normal population. Interestingly, patients with recurrent unipolar depression in remission had no more IBS-like symptoms than controls, indicating that the gastrointestinal symptoms may resolve when depression is treated to remission. Patients with IBS have an increased mid-frequency power in rest and in supine position (after tilt test) compared to healthy controls indicating an increased sympathetic ANS drive. The symptoms of diarrhea and early satiety has in the litterature been associated to the stimulation of corticotropin releasing hormone (CRH) receptors and was also in our study related to HPA axis function tested by a low dose dexamethasone test. Interestingly both hypo- and hyperfunction of the HPA axis was related to these symptoms in control subjects. The val158met COMT polymorphism was associated to IBS-like symptoms. Control subjects with IBS-like symptoms (defined by the upper quartile in total GSRS-IBS score) had a higher frequency of the met/met and a significantly lower frequency of the val/met genotype. Also patients with IBS tended to have a lower frequency of the heterozygous val/met genotype so we conclude that this genotype may be protective against IBS/IBS like symptoms. In addition, the val/val genotype in patients with IBS was associated to diarrhea symptoms. Conclusions: Our results support the model of an emotional motor system in the genesis of functional gastrointestinal symptoms by the finding of the association of IBS-like symptoms and mood disturbances, and by finding alterations in the peripheral limbs of EMS (ANS, HPA axis and catecholamines) in subjects with IBS and IBS-like symptoms.

Although musculoskeletal disorders (MSDs) and other health complaints are an occupational problem for ambulance personnel, there is a lack of knowledge regarding work-related factors associated with MSDs and other health complaints. The overall aim of this thesis was to investigate the relationships between occupational demands, individual characteristics and health-related outcomes among ambulance personnel. A random sample of 234 female and 953 male ambulance personnel participated in a national questionnaire survey on work-related factors, and musculoskeletal and other health complaints. Physical demands was associated with activity limitation due to neck-shoulder and low-back complaints among the female personnel. Among the male personnel, physical demands was associated with low-back complaints and activity limitation due to low-back complaints. Psychological demands was significantly associated with neck-shoulder complaints, sleeping problems, headache and stomach symptoms among both female and male ambulance personnel. Worry about work conditions was associated with musculoskeletal disorders and sleeping problems, headache and stomach symptoms. A local sample of 26 ambulance personnel was followed during a 24-hour work shift and for the next two work-free days. Subjective stress- and energy levels, and cortisol levels were measured at regular intervals, and heart rate was registered continuously by electrocardiogram (ECG). Autonomic reactivity to standardized tests before (pre-work) and at the end of the work shift (post-work) was also investigated. For the whole group, baseline values of heart rate were higher pre-work than post-work, but autonomic reactivity did not differ. Increased reactivity to the mental test, modest deviation in heart rate variability (HRV) pattern during the late night hours at work and higher morning cortisol values during work than during leisure time were observed in personnel with many health complaints, but not among their co-workers without or with few complaints. Ambulance personnel with many health complaints also reported higher psychological demands and tended to be more worried about work conditions. Heart rate (HR), lactate level (LL) and perceived exertion (RPE) were investigated in 17 female and 48 male ambulance personnel during a simulated standardized work task “carry a loaded stretcher”. The ambulance personnel had to carry the loaded stretcher (920 N) up and down three flights of stairs twice. The high physiological strain (HR, LL, RPE) for the male, and near or at maximal strain for the female ambulance personnel, implied the importance to identify what kind of physical capacity is most important for ambulance personnel. Therefore, the explained variance of developed fatigue by tests of cardiorespiratory capacity, muscular strength and endurance, and coordination was investigated. The results showed that VO2max and isometric back endurance were important predictors for development of fatigue when carrying a loaded stretcher. The influence of body size on the relationships between maximal strength and functional performance was investigated in a methodological study. The results confirm that the assessment of physical performance could be confounded by the body weight. Therefore, the models for explaining development of fatigue when carrying the loaded stretcher were adjusted for height and weight. Including height in the models significantly increased the explained variance of accumulated lactate among female, but not among male personnel. Lactate levels were higher among short compared to tall female personnel. Weight had no effect on any of the models. In conclusion, the national survey showed that self-reported physical demands was a risk factor of having MSDs, and that self-reported psychological demands and worry about work were important risk factors of having MSDs and other health complaints. Stress monitoring of ambulance personnel during work and leisure time showed that physiological and subjective stress markers did not show any differences between the 24-hour ambulance work shift and leisure time afterwards. However, ambulance personnel with many health complaints had certain physiological changes during the work shift in comparison with the next two work-free days. The physiological and subjective responses during carrying a loaded stretcher, especially among the female ambulance personnel, showed that female and male ambulance personnel could be exposed to internal exposures at different levels when performing the same work task. A better understanding of the relationships between occupational demands and health-related outcomes require further studies on age- and gender matched groups in long-term perspective studies.

Anemia is common in patients with chronic kidney disease (CDK), contributes to reduced Quality of Life (QoL) and is associated with cardiovascular disease, morbidity and mortality. Epoetin raises hemoglobin (Hb) and increases QoL and physical exercise capacity. Because of concerns about safety and economics, current anemia treatment with epoetin aims to achieve subnormal Hb (110-120 g/l). Normalization of Hb may be of additional benefit regarding QoL and cardiovascular effects. The present study examines the effects of Hb normalization with epoetin on safety variables, QoL, graft function after kidney transplantation, dialysis adequacy, hemorheology, hemodynamics and cardiac autonomic function in CKD patients. In a randomized, multicenter study comprising 416 pre-dialysis and dialysis patients no difference was observed between patients treated to a normal or a subnormal Hb level on mortality, thrombovascular events, serious adverse events, vascular access thrombosis and residual renal function. QoL was enhanced in a subgroup of hemodialysis patients. Pretransplant epoetin treatment directed toward normal Hb levels did not result in worse graft function during 6 postoperative months. Dialysis adequacy was reduced in a subgroup of hemodialysis patients after normalization of Hb. The blood flow properties of pre-dialysis patients were altered. The hemorheological investigation demonstrated that Hb normalization caused a parallel increase in hematocrit and blood viscosity without other hemorheological changes. While the total peripheral resistance index increased, the cardiac index (CI) decreased. In a separate study cardiac autonomic function, measured by heart rate variability, was decreased in pre-dialysis patients. It was improved, but not fully normalized, by Hb normalization. On the basis of this study, Hb normalization with epoetin appears to be safe and increases QoL in hemodialysis patients though may result in lower dialysis adequacy and increased blood pressure. A reduction in CI and improved cardiac autonomic function indicate a positive effect on cardiovascular function.

Epidemiological studies have shown strong and consistent associations between exposure to air pollution and increases in morbidity and mortality. Key air pollutants that have been identified include fine particulate matter (PM) and ozone (O3), both major contributors to smog. However, there is a lack of understanding of the mechanisms involved and the relative contributions of individual pollutants. A controlled human exposure facility was used to carry out inhalation studies of concentrated ambient fine particles (CAP), O3, CAP+O3 and filtered air following a randomized design. Exposures were 2 hrs in duration at rest. Subjects included mild asthmatics and non-asthmatics. This thesis focuses on acute cardiovascular responses including blood pressure (BP), brachial artery reactivity (flow-mediated dilatation [FMD]) and markers of systemic inflammation (blood neutrophils and interleukin [IL]-6). Results showed that for CAP-containing exposures (CAP, CAP+O3) there were small but significant transient increases in diastolic BP (DBP) during exposures. Furthermore, neutrophils and IL-6 increased 1 - 3 hrs after and FMD decreased 20 hrs after CAP-containing exposures. Responses to O3 were smaller, comparable to filtered air. The data suggests that adverse responses were mainly driven by PM. The DBP increase was rapid-developing and quick to dissipate, which points to an autonomic irritant response. The magnitude of the DBP increase was strongly negatively associated with the high frequency component of heart rate variability, suggesting parasympathetic withdrawal as a mechanism. In comparison, IL-6, neutrophil and FMD responses were slower to develop, indicative of an inflammatory mechanism. An intriguing finding was that IL-6 increased 3 hrs after CAP, but not after CAP+O3. Further investigation revealed that exposure to CAP+O3 in some individuals may trigger a reflex inhibition of inspiration, decreasing their tidal volume and inhaled pollutant dose, leading to a reduction in systemic IL-6, a potential protective mechanism. Together the findings support the epidemiological evidence of adverse fine PM health effects. Many questions remain to be answered about the health effects of air pollution including a better understanding of how inhaled pollutants result in cardiovascular effects. It is hoped that the insights gained from this thesis will advance the understanding of air pollution health effects.

Epidemiological studies have shown strong and consistent associations between exposure to air pollution and increases in morbidity and mortality. Key air pollutants that have been identified include fine particulate matter (PM) and ozone (O3), both major contributors to smog. However, there is a lack of understanding of the mechanisms involved and the relative contributions of individual pollutants. A controlled human exposure facility was used to carry out inhalation studies of concentrated ambient fine particles (CAP), O3, CAP+O3 and filtered air following a randomized design. Exposures were 2 hrs in duration at rest. Subjects included mild asthmatics and non-asthmatics. This thesis focuses on acute cardiovascular responses including blood pressure (BP), brachial artery reactivity (flow-mediated dilatation [FMD]) and markers of systemic inflammation (blood neutrophils and interleukin [IL]-6). Results showed that for CAP-containing exposures (CAP, CAP+O3) there were small but significant transient increases in diastolic BP (DBP) during exposures. Furthermore, neutrophils and IL-6 increased 1 - 3 hrs after and FMD decreased 20 hrs after CAP-containing exposures. Responses to O3 were smaller, comparable to filtered air. The data suggests that adverse responses were mainly driven by PM. The DBP increase was rapid-developing and quick to dissipate, which points to an autonomic irritant response. The magnitude of the DBP increase was strongly negatively associated with the high frequency component of heart rate variability, suggesting parasympathetic withdrawal as a mechanism. In comparison, IL-6, neutrophil and FMD responses were slower to develop, indicative of an inflammatory mechanism. An intriguing finding was that IL-6 increased 3 hrs after CAP, but not after CAP+O3. Further investigation revealed that exposure to CAP+O3 in some individuals may trigger a reflex inhibition of inspiration, decreasing their tidal volume and inhaled pollutant dose, leading to a reduction in systemic IL-6, a potential protective mechanism. Together the findings support the epidemiological evidence of adverse fine PM health effects. Many questions remain to be answered about the health effects of air pollution including a better understanding of how inhaled pollutants result in cardiovascular effects. It is hoped that the insights gained from this thesis will advance the understanding of air pollution health effects.