Analisar as características do trabalho realizado por trabalhadores de Enfermagem atuantes na área hospitalar e a relação com a presença de Ansiedade, de Depressão e de Estresse, assim como, com o cortisol capilar. Método: Estudo descritivoanalítico, transversal, com abordagem quantitativa, desenvolvido no município de São Carlos (SP), com 164 profissionais da equipe de enfermagem da área hospitalar, entre eles auxiliares, técnicos de enfermagem e enfermeiros, que trabalhavam nos setores Unidade de Internação, Urgência e Emergência, Unidade de Terapia Intensiva Adulto, Unidade Coronariana e o Isolamento. Os dados foram coletados por meio de instrumento semiestruturado de autopreenchimento destinado a caracterizar a população e, também, por dois outros instrumentos: a Escala Hospitalar de Ansiedade e Depressão e a Escala para Avaliação do Estresse Percebido. Realizada a coleta de amostras de cabelos dos participantes por meio do kit Diasource específico para Cortisol ELISA (Enzyme-Linked Immunosorbent Assay - KAPDB290). A pesquisa foi previamente aprovada por Comitê de Ética em Pesquisa, protocolo CAAE: 55839216.5.0000.5393. A prevalência de depressão tomada como base para o cálculo amostral foi assumida como desconhecida, o valor de prevalência de 50%, que resulta em um tamanho amostral que contemple qualquer valor de P. O programa do cálculo amostral foi o R versão 3.1.2. Os testes estatísticos utilizados para a realização das análises foram o Pearson Chi-Square, Qui-quadrado, Coeficiente de Correlação de Spearman-?, Mann-Whitney e Kruskal Wallis. Resultados: Por meio das análises descritivas (n=164) constatou-se que a maioria dos entrevistados é constituída por técnicos de enfermagem (62,19%), do sexo feminino (80,49%), com idade entre 31 a 50 anos (57,93%), casados/com companheiro (44,51%), efetivos, atuando na profissão entre 0 a 10 anos (76,22%), trabalhando em unidades de internação (48,17%), no turno diurno (52,44%), aos finais de semana (93,9%), não tabagistas (81,7%) e nem consumidores de bebidas alcoólicas (60,4%). Em relação ao cortisol (n=161), 47,8% mostraram nível acima do normal; 23,8% apresentam estresse moderado, 20,1% estresse alto e 12,8% estresse muito alto; já 44,51% apresentaram Ansiedade e 24,39% Depressão. Segundo os testes estatísticos, os níveis de cortisol não influenciaram no Estresse percebido, pois não houve diferença no seu total, tanto para os trabalhadores que apresentam ou não Ansiedade. Não houve diferenças estatísticas entre os setores hospitalares das áreas críticas e não críticas e também nos níveis de Estresse, de Ansiedade e de Depressão entre as categorias de trabalhadores. Conclusão: As hipóteses foram parcialmente confirmadas, pois ocorreram alterações nos níveis do cortisol capilar, que estavam acima do recomendado. O estudo trouxe contribuições importantes relacionados ao biomarcador cortisol capilar, ao Estresse, à Ansiedade e à Depressão. Instituições hospitalares deveriam oferecer programas com intervenções na área ocupacional e medidas preventivas para amenizar alterações de saúde mental nos trabalhadores de enfermagem / Objective: To analyze the characteristics of the work performed by Nursing workers working in the hospital area and the relationship with the presence of Anxiety, Depression and Stress, as well as with capillary cortisol. Method: A cross-sectional descriptiveanalytical study with a quantitative approach developed in the city of São Carlos (SP), with 164 professionals from the nursing team of the hospital area, including auxiliaries, nursing technicians and nurses, who worked in the Inpatient, Urgency and Emergency, Adult Intensive Care Unit, Coronary Unit and Isolation. Data were collected through a semistructured auto-fill instrument to characterize the population and also by two other instruments: the Hospital Anxiety and Depression Scale and the Perceived Stress Assessment Scale. The participant\'s hair samples were collected using the Diasource specific kit for Cortisol ELISA (Enzyme-Linked Immunosorbent Assay - KAPDB290). The research was previously approved by the Research Ethics Committee, protocol CAAE: 55839216.5.0000.5393. The prevalence of depression taken as the basis for the sample calculation was assumed to be unknown, the prevalence value of 50%, which results in a sample size that contemplates any value of P. The program of the sample calculation was R version 3.1.2. The statistical tests used were the Pearson Chi-Square, Chi-square, Spearman-?, Mann-Whitney and Kruskal Wallis Correlation Coefficient. Results: Descriptive analyzes (n = 164) found that the majority of the interviewees were nursing technicians (62.19%), female (80.49%), aged 31-50 years (57.93%), married / with partner (44.51%), working in the profession between 0 and 10 years (76.22%), working in hospitalization units (48.17%), day shift (52.44%), at weekends (93.9%), non-smokers (81.7%) and consumers of alcoholic beverages (60.4%). In relation to cortisol (n = 161), 47.8% showed a level above normal; 23.8% had moderate stress, 20.1% had high stress and 12.8% had very high stress; and 44.51% presented Anxiety and 24.39% Depression. According to the statistical tests, the cortisol levels did not influence the perceived Stress, because there was no difference in its total, both for the workers that present or not Anxiety. There were no statistical differences between the hospital sectors of the critical and non-critical areas and also the levels of Stress, Anxiety and Depression among the categories of workers. Conclusion: The hypotheses were partially confirmed, as there were alterations in capillary cortisol levels, which were higher than recommended. The study brought important contributions related to the biomarker capillary cortisol, to Stress, Anxiety and Depression. Hospital institutions should offer programs with interventions in the occupational area and preventive measures to alleviate mental health changes in nursing workers

Stress activates a number of endocrine pathways that alter an animal's physiology in a manner which can result in undesirable meat quality. Animals frequently exhibit meat quality defects, including ecchymosis, at slaughter due to the stress of slaughter. This thesis explores how stress related hormones interact with adrenergic receptors to alter muscle and vascular physiology. Fallow deer were exposed to either a transciptional regulator (hydrocortisone), a beta adrenergic recptor agonist (clenbuterol) or a beta adrenergic receptor antagonist (propranolol). The administration of hydrocortisone resulted in a negative feed-back type reduction in circulating cortisol. Animals treated with propranolol and clenbuterol displayed less severe eccymosis. These results indicated that the beta 2 adrenergic receptor (B2AR) is important in controlling ecchymosis severity. B2AR was also found to be important in mediating vascular dynamics, growth and energy pathways. To investigate how adrenergic receptors alter skeletal muscle gene expression and meat quality, an in vivo wistar rat model was developed in conjunction with in vitro muscle cell (L6) experiments. Gene expression of B2AR, its associated kinase (BARK) and collagen type III, prolyl- 4-hydroxylase (P4Hy) was measured in rat muscle and L6 cells. Following exposure to clenbuterol and hydrocortisone, growth and meat quality were determined. The L6 experiments revealed that gene expression following exposure to hydrocortisone and B2AR ligands paralleled the in vivo rat changes in B2AR, BARK, collagen type III, and P4Hy gene expression. In both L6 and wistar rat models the B2AR and BARK genes are similarly expressed following clenbuterol exposure. Both rats and deer exposed to clenbuterol had significant increases in growth rate and a reduction of intramuscular fat. The B2AR therefore appears to be a major mediator of many interrelated events including energy distribution, growth and vascular response to stress. Habituating animals to stress stimuli may increase their coping ability and improve welfare and meat quality. / Doctor of Philosophy (PhD)

Cortisol, the principal glucocorticoid secreted from the adrenal glands, is essential for life. Healthy cortisol levels are maintained through negative feedback on the central nervous system (CNS) – pituitary stimulatory apparatus which regulates production of adrenocorticotropin (ACTH) and contains a light–entrained intrinsic CNS driven diurnal rhythm. Cortisol participates in a regulatory mechanism where inflammatory cytokines stimulate cortisol release and cortisol in turn suppresses cytokine release. The effects of cortisol in inflammatory states include elevating blood pressure and metabolic regulation. This thesis contains three exploratory studies examining circulating cortisolaemia using the best available methodologies (total and free cortisol and corticosteroid-binding globulin (CBG)) in clinical states characterized by immune activation/ inflammation and altered blood pressure. These clinical states include: (1) septic shock, (2) hypertensive disorders of pregnancy and (3) obesity-induced hypertension. Prior to the studies described here, little was know about cortisolaemia in these common pathological states. Septic shock is a life threatening condition that complicates severe infection and is characterized by systemic inflammation and refractory hypotension. High plasma total cortisol levels and attenuated responses to synthetic ACTH stimulation are associated with increased mortality. The use of corticosteroids in septic shock has been highly controversial for decades, however recent trials have reported haemodynamic and survival benefits associated with the use of physiologic steroid replacement in patients with relative adrenal insufficiency (RAI) – currently defined as a total cortisol increment of 248 nmol/L or less following ACTH (250 μg) stimulation. However, CBG and albumin levels fall by around 50% with an increase in plasma free cortisol in critical illness. Hence, total cortisol may not reflect the biologically active free (unbound) cortisol, suggesting that standard assays for plasma cortisol (which measure total plasma cortisol) underestimate HPA axis activity. In this study, we have showed that plasma free cortisol is a better guide to circulating glucocorticoid activity in systemic infection than total cortisol. We have also validated the use of Coolens’ method in estimating free cortisol in systemic infection, using plasma total cortisol and CBG measurements as plasma free cortisol is not performed in clinical laboratories. Free cortisol measurement allows better categorization of RAI and non-RAI groups with a free cortisol increment of 110 nmol/L as cut-off. Moreover, we have shown that survivors of RAI have normal adrenocortical function on follow-up testing suggesting a lack of functional adrenal reserve rather than adrenal damage during critical illness. Larger randomized controlled trials will be required to redefine RAI using free cortisol measurements and relate that to clinical outcomes and responses to corticosteroid therapy. Nitric oxide (NO) is normally produced in the endothelium by the constitutive form of the NO synthase and this physiologic production is important for blood pressure regulation and blood flow distribution. Studies have shown that an overproduction of NO by the inducible form of NO synthase (iNOS) may contribute to the hypotension, cardiodepression and vascular hyporeactivity in septic shock. Clinical studies of non-selective inhibitors of the L-arginine nitric oxide pathway showed increased mortality from cardiovascular complications. However, glucocorticoids, which improve vasopressor sensitivity, may act by partially suppressing NO synthesis through selective direct inhibition of iNOS, and suppression of inflammatory cytokine synthesis. Hence, plasma nitrate/ nitrite (NOx) levels may provide a titratable end point to individualize glucocorticoid therapy in sepsis. The NOx study in this thesis showed that cortisol (total and free), CBG and NOx correlated to illness severity. Free cortisol, and to a lesser extent total cortisol, but not NOx levels, predicted septic shock. NOx levels were characteristically stable within individuals but inter-individual differences were only partly accounted for by illness severity or renal dysfunction. NOx levels correlated weakly with cortisol, did not relate to the need for vasopressors and were not suppressed by hydrocortisone treatment. Thus, NOx is not a suitable target for glucocorticoid therapy in septic shock. Pregnancy is the only sustained physiologic state of hypercortisolism in humans. A large body of data suggests that excessive foetal and prenatal glucocorticoid exposure leads to reduced birth weight and adverse health in offspring such as elevated blood pressure and insulin resistance. Pre-eclampsia and gamete donor pregnancies are associated with immune activation, elevated inflammatory cytokines as well as elevated blood pressure. Prior to the study described in this thesis however, there was no prospective data on maternal cortisolaemia in these complicated pregnancies. My study has demonstrated for the first time that there was a substantial fall in plasma CBG levels in the last few weeks of gestation with a corresponding rise in free cortisol in normal pregnancy, a finding obscured for methodological reasons in past studies. This free cortisol elevation in late pregnancy may facilitate organ maturation in the foetus and perhaps prepare the mother for the metabolic demands of labour. In pre-eclampsia and gestational hypertension, plasma CBG, total and free cortisol levels were lower in late third trimester; and in IUGR, plasma CBG levels were suppressed from 28 weeks gestation until delivery but with no significant difference in plasma total and free cortisol. Women with assisted reproduction using donor gametes/ embryos had significantly lower plasma CBG, total and free cortisol levels even in those with normal pregnancy outcomes. Low CBG may be due to reduced synthesis or enhanced inflammation-driven degradation. Low maternal cortisol may be due to a lack of placental corticotropin-releasing hormone, or reduced maternal ACTH, driving cortisol production. This unanticipated maternal hypocortisolism in complicated pregnancies may trigger precocious activation of the foetal HPA axis and could have implications for postnatal and adult health. Speculatively, since excess prenatal GCs increase HPA axis activity, we proposed that maternal hypocortisolism may predispose to the hypocortisolaemic state characterized by fatigue, pain and stress sensitivity, in offspring. The third state of immune/ inflammatory activation associated with blood pressure dysregulation studied in this thesis is obesity. The epidemiologic relationship between obesity and hypertension is widely recognised. Central obesity in particular has been associated with exaggerated HPA responses to stimuli. Studies of severe dieting and starvation resulted in hypercortisolism and a significant decrease in CBG. The HPA axis and the renin-angiotensin-aldosterone system (RAAS) have been implicated in the pathophysiology of obesity-induced hypertension. However, there is little data on the effect of moderate weight loss (30% caloric restriction) on adrenocortical function, and the relation of adrenal hormones to altered blood pressure with weight loss. In this study, measures of HPA axis and RAAS and blood pressure monitoring were performed in twenty-five obese subjects before and after a 12-week diet program (6000kJ/day). Short-term, moderate weight loss (mean 8.5 kg) was associated with a small reduction in blood pressure (mean arterial pressure 6 mmHg) and significantly reduced levels of aldosterone and renin but not cortisol levels. These findings suggest that aldosterone may have an important role in the blood pressure reduction with weight loss via a renin mediated mechanism, perhaps involving renal sympathetic tone. In contrast to severe caloric restriction, HPA axis activation does not occur with moderate weight loss. This suggests a threshold effect of weight loss on the HPA axis where greater caloric restriction is required for HPA stimulation, or a counterbalancing of central and direct adrenal effects on HPA axis function. Overall, these three exploratory studies have provided novel data on HPA axis function in systemic infection, pregnancy and in diet-induced weight loss. Each study offers a basis for further studies of HPA axis function in these disorders. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1289330 / Thesis(Ph.D.)-- School of Medicine, 2007.

Do endocrine systems influence personality and social behavior? Although animal research has identified several hormone-behavior relationships and the mechanisms that give rise to them, much less is known about hormones and social functioning in humans. This dissertation used three large data sets to investigate whether testosterone and cortisol were related to variation in personality constructs (Study 1), leadership behaviors (Study 2), and economic decision making (Studies 3 and 4). Study 1 revealed that basal testosterone was negatively associated with conscientiousness, basal cortisol was negatively associated with extraversion but positively associated with social dominance orientation, and the interaction between testosterone and cortisol was associated with the implicit power motive. Study 2 found that the testosterone-cortisol interaction predicted leadership behaviors, and Study 3 showed that basal testosterone as well as change in cortisol predicted economic decisions in the Hawk-Dove Game. Finally, Study 4 demonstrated that aggression predicted decisions to punish unfair monetary offers in the Ultimatum and Third Party Punishment Games. Aggression was also related to women's changes in testosterone from before to after the games. Taken together, these studies provide important evidence that testosterone and cortisol are related to personality, leadership, and social decision making. More broadly, this dissertation lays the empirical foundation for further inquiry on the complex biological systems that regulate personality and social behavior.

There are a number of links between the endocrine system and the nervous system. In this study, the impact of ischemic stroke on the endocrine system was investigated. Elderly volunteers were studied because data regarding the influence of advanced age on endocrine parameters were lacking. Only small differences in pituitary-thyroid and pituitary-adrenal hormone axes were found between two groups of elderly patients, 60 and 80 years of age. The 80-year-old age group had a lower thyrotropin response to thyrotropin releasing hormone (TRH) and a decline in dopamine excretion. Patients with acute ischemic stroke showed a pronounced hypercortisolism studied by the dexamethasone test and urine free cortisol measurements. In multiple regression analyses, postdexamethasone cortisol levels were positively correlated to proximity of the lesion to the frontal pole of the brain and disorientation. Urine cortisol levels were predicted by limb paresis, disorientation and body temperature. High cortisol excretion was associated with a worse functional outcome. Norepinephrine excretion was correlated to urine cortisol levels and to motor impairment. Patients with acute stroke had elevated free thyroxin indices. A paradoxical growth hormone response to TRH was found in the majority of stroke patients. In a multiple regression model disorientation was negatively correlated to thyrotropin response after TRH and positively correlated to prolactin response. Growth hormone response to TRH was associated with extensive paresis. In a cohort study diabetic and non-diabetic patients were prospectively studied after an initial stroke. Diabetes mellitus adversely influenced survival, the risk for a recurrent stroke and myocardial infarction. / <p>S. 1-66: sammanfattning, s. 69-190: 6 uppsatser</p> / digitalisering@umu

Cortisol, the principal glucocorticoid secreted from the adrenal glands, is essential for life. Healthy cortisol levels are maintained through negative feedback on the central nervous system (CNS) – pituitary stimulatory apparatus which regulates production of adrenocorticotropin (ACTH) and contains a light–entrained intrinsic CNS driven diurnal rhythm. Cortisol participates in a regulatory mechanism where inflammatory cytokines stimulate cortisol release and cortisol in turn suppresses cytokine release. The effects of cortisol in inflammatory states include elevating blood pressure and metabolic regulation. This thesis contains three exploratory studies examining circulating cortisolaemia using the best available methodologies (total and free cortisol and corticosteroid-binding globulin (CBG)) in clinical states characterized by immune activation/ inflammation and altered blood pressure. These clinical states include: (1) septic shock, (2) hypertensive disorders of pregnancy and (3) obesity-induced hypertension. Prior to the studies described here, little was know about cortisolaemia in these common pathological states. Septic shock is a life threatening condition that complicates severe infection and is characterized by systemic inflammation and refractory hypotension. High plasma total cortisol levels and attenuated responses to synthetic ACTH stimulation are associated with increased mortality. The use of corticosteroids in septic shock has been highly controversial for decades, however recent trials have reported haemodynamic and survival benefits associated with the use of physiologic steroid replacement in patients with relative adrenal insufficiency (RAI) – currently defined as a total cortisol increment of 248 nmol/L or less following ACTH (250 μg) stimulation. However, CBG and albumin levels fall by around 50% with an increase in plasma free cortisol in critical illness. Hence, total cortisol may not reflect the biologically active free (unbound) cortisol, suggesting that standard assays for plasma cortisol (which measure total plasma cortisol) underestimate HPA axis activity. In this study, we have showed that plasma free cortisol is a better guide to circulating glucocorticoid activity in systemic infection than total cortisol. We have also validated the use of Coolens’ method in estimating free cortisol in systemic infection, using plasma total cortisol and CBG measurements as plasma free cortisol is not performed in clinical laboratories. Free cortisol measurement allows better categorization of RAI and non-RAI groups with a free cortisol increment of 110 nmol/L as cut-off. Moreover, we have shown that survivors of RAI have normal adrenocortical function on follow-up testing suggesting a lack of functional adrenal reserve rather than adrenal damage during critical illness. Larger randomized controlled trials will be required to redefine RAI using free cortisol measurements and relate that to clinical outcomes and responses to corticosteroid therapy. Nitric oxide (NO) is normally produced in the endothelium by the constitutive form of the NO synthase and this physiologic production is important for blood pressure regulation and blood flow distribution. Studies have shown that an overproduction of NO by the inducible form of NO synthase (iNOS) may contribute to the hypotension, cardiodepression and vascular hyporeactivity in septic shock. Clinical studies of non-selective inhibitors of the L-arginine nitric oxide pathway showed increased mortality from cardiovascular complications. However, glucocorticoids, which improve vasopressor sensitivity, may act by partially suppressing NO synthesis through selective direct inhibition of iNOS, and suppression of inflammatory cytokine synthesis. Hence, plasma nitrate/ nitrite (NOx) levels may provide a titratable end point to individualize glucocorticoid therapy in sepsis. The NOx study in this thesis showed that cortisol (total and free), CBG and NOx correlated to illness severity. Free cortisol, and to a lesser extent total cortisol, but not NOx levels, predicted septic shock. NOx levels were characteristically stable within individuals but inter-individual differences were only partly accounted for by illness severity or renal dysfunction. NOx levels correlated weakly with cortisol, did not relate to the need for vasopressors and were not suppressed by hydrocortisone treatment. Thus, NOx is not a suitable target for glucocorticoid therapy in septic shock. Pregnancy is the only sustained physiologic state of hypercortisolism in humans. A large body of data suggests that excessive foetal and prenatal glucocorticoid exposure leads to reduced birth weight and adverse health in offspring such as elevated blood pressure and insulin resistance. Pre-eclampsia and gamete donor pregnancies are associated with immune activation, elevated inflammatory cytokines as well as elevated blood pressure. Prior to the study described in this thesis however, there was no prospective data on maternal cortisolaemia in these complicated pregnancies. My study has demonstrated for the first time that there was a substantial fall in plasma CBG levels in the last few weeks of gestation with a corresponding rise in free cortisol in normal pregnancy, a finding obscured for methodological reasons in past studies. This free cortisol elevation in late pregnancy may facilitate organ maturation in the foetus and perhaps prepare the mother for the metabolic demands of labour. In pre-eclampsia and gestational hypertension, plasma CBG, total and free cortisol levels were lower in late third trimester; and in IUGR, plasma CBG levels were suppressed from 28 weeks gestation until delivery but with no significant difference in plasma total and free cortisol. Women with assisted reproduction using donor gametes/ embryos had significantly lower plasma CBG, total and free cortisol levels even in those with normal pregnancy outcomes. Low CBG may be due to reduced synthesis or enhanced inflammation-driven degradation. Low maternal cortisol may be due to a lack of placental corticotropin-releasing hormone, or reduced maternal ACTH, driving cortisol production. This unanticipated maternal hypocortisolism in complicated pregnancies may trigger precocious activation of the foetal HPA axis and could have implications for postnatal and adult health. Speculatively, since excess prenatal GCs increase HPA axis activity, we proposed that maternal hypocortisolism may predispose to the hypocortisolaemic state characterized by fatigue, pain and stress sensitivity, in offspring. The third state of immune/ inflammatory activation associated with blood pressure dysregulation studied in this thesis is obesity. The epidemiologic relationship between obesity and hypertension is widely recognised. Central obesity in particular has been associated with exaggerated HPA responses to stimuli. Studies of severe dieting and starvation resulted in hypercortisolism and a significant decrease in CBG. The HPA axis and the renin-angiotensin-aldosterone system (RAAS) have been implicated in the pathophysiology of obesity-induced hypertension. However, there is little data on the effect of moderate weight loss (30% caloric restriction) on adrenocortical function, and the relation of adrenal hormones to altered blood pressure with weight loss. In this study, measures of HPA axis and RAAS and blood pressure monitoring were performed in twenty-five obese subjects before and after a 12-week diet program (6000kJ/day). Short-term, moderate weight loss (mean 8.5 kg) was associated with a small reduction in blood pressure (mean arterial pressure 6 mmHg) and significantly reduced levels of aldosterone and renin but not cortisol levels. These findings suggest that aldosterone may have an important role in the blood pressure reduction with weight loss via a renin mediated mechanism, perhaps involving renal sympathetic tone. In contrast to severe caloric restriction, HPA axis activation does not occur with moderate weight loss. This suggests a threshold effect of weight loss on the HPA axis where greater caloric restriction is required for HPA stimulation, or a counterbalancing of central and direct adrenal effects on HPA axis function. Overall, these three exploratory studies have provided novel data on HPA axis function in systemic infection, pregnancy and in diet-induced weight loss. Each study offers a basis for further studies of HPA axis function in these disorders. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1289330 / Thesis(Ph.D.)-- School of Medicine, 2007.

Thèse (Ph.D.)--Université Laval, 2007. / Anglais ou français ; avec des résumés en anglais et en français. Bibliogr.: f. 213-237. Publié aussi en version électronique dans la Collection Mémoires et thèses électroniques.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 5 uppsatser.

Thesis (Ph. D.)--University of Oklahoma. / Includes bibliographical references.

The aim of this thesis was to measure the kinetics of photochemical degradation of hydrocortisone in heterogeneous photocatalytic reaction on immobilized TiO2 and in homogeneous photocatalytic reaction with Fe(III) using UV-VIS and HPLC for measuring the degradation kinetics.