Urinary Excretion Of Epinephrine Research Articles

Psychosocial Stressors in Psychosomatic Cardiology

The definition of a psychosocial stressor and reactions to it is discussed in relation to individual and environmental factors. The relation of this model to psychophysiological stress reactions and regeneration, as well as its significance for cardiovascular diseases, is described. Three classes of psychosocial stressors (life changes, work conditions, and family conflicts) are then described in relation to cardiovascular illness and risk factors. Particular emphasis is on longitudinal studies of patients. Heart contractility and urinary adrenaline excretion are discussed in detail. Epidemiological data on psychosocial stressors and cardiovascular disease outcomes (mainly myocardial infarction) are also discussed.

LPIN1 is a new target gene for essential hypertension.

We previously showed Lipin1 (LPIN1) to be a candidate gene for essential hypertension by genome-wide association studies. LPIN1 encodes the Lipin 1 protein, which contributes to the maintenance of lipid metabolism and glucose homeostasis. However, little is known about the association between LPIN1 and blood pressure (BP). We evaluated the BP of LPIN1-deficient [fatty liver dystrophy (fld)] mice and explored related mechanisms. Fld mice have very low expression of LPIN1 and exhibit fatty liver, hypertriglyceridemia, insulin resistance and peripheral neuropathy. Fld mice had significantly elevated SBP and heart rate (HR) throughout the day as measured by a radiotelemetric method. Diurnal variation of SBP and HR was also absent in fld mice. Furthermore, urinary excretion of adrenaline and noradrenaline by fld mice was significantly higher compared with that of control mice. The BP response of fld mice to clonidine (a centrally acting α2-adrenergic receptor agonist) was greater than that of control mice. However, levels of Angiotensinogen and Renin 1 mRNA and urinary nitric oxide excretion were comparable between the two groups. The decrease in SBP at 8 weeks after fat grafting surgery was significantly greater in the transplant group compared with the sham operated group. The elevated BP in fld mice may result from activation of the sympathetic nervous system through decreased levels of adipose cytokines. These results indicate that LPIN1 plays a crucial role in blood pressure regulation and that LPIN1 is a new target gene for essential hypertension.

Metastatic pheochromocytoma and paraganglioma: signs and symptoms related to catecholamine secretion

BackgroundThe presence or future development of metastatic pheochromocytomas or paragangliomas (mPPGLs) can be difficult to diagnose or predict at initial presentation. Since production of catecholamines from mPPGLs is different from non-metastatic tumors (non-mPPGLs), this study aimed to clarify whether presenting catecholamine-related signs and symptoms (cSS) might also differ.MethodsThe study included 249 patients, 43 with mPPGL and 206 with non-mPPGL. Clinical data at the time of biochemical diagnosis (i.e. at entry into the study) were used to generate a cumulative score of cSS for each patient.ResultsPatients with mPPGL were significantly younger (43.3 ± 14 vs. 48.9 ± 16.1 years) and included a lower proportion of females (39.5% vs. 60.7%) than patients with non-mPPGLs. Frequencies of signs and symptoms did not differ between the two groups. Patients with mPPGLs had lower (P < 0.001) urinary excretion of epinephrine (3.5 (IQR, 1.9—6.5) µg/day) than those with non-mPPGLs (19.1 (IQR, 4.3—70.2) µg/day). There was no difference in urinary excretion of norepinephrine. In patients with mPPGLs a high cSS score was associated with high urinary excretion of norepinephrine and normetanephrine. In contrast, in patients with non-mPPGLs, a high cSS was associated with high urinary excretion of epinephrine and metanephrine.ConclusionAlthough presenting signs and symptoms were associated with production of norepinephrine in patients with mPPGLs and of epinephrine in patients with non-mPPGLs, there were no differences in signs and symptoms between the two groups. Therefore, consideration of signs and symptoms does not appear helpful for distinguishing patients with and without mPPGLs.

A food ingredient containing phytoecdysteroids and polyphenols from quinoa grain: technology and physiological and biochemical evaluation in vivo

An effective technological approach to produce adaptogenic microingredients is to concentrate plant biologically active substances via sorption on various matrices. The aim was to develop and evaluate in vivo the phytoecdysteroids and flavonoids concentrate extracted from quinoa grain and sorbed on the coagulated chicken egg protein. The consecutive extraction of phytoecdysteroids and flavonoids was conducted followed by sorption on the protein. The in vivo experiment was performed during 37 days using Wistar male rats. The developed concentrate was added into the diet of experimental animals in the dose 0.59±0.02 g/100 g of diet. As a stress model we used daily 40-min immobilization and exhaustive 3-hour immobilization at the end of the experiment. Urinary catecholamines content was determined, blood corticosterone, malon dialdehyde, glutathione reductase and superoxide dismutase content was determined. Phytoecdysteroids and flavonoids were concentrated 20 and 80 times respectively compared to the initial raw materials. The concentrate consumption neutralized negative effect of immobilization stress on anxiety level of Wistar rats. The significant decrease in urinary excretion of adrenaline and noradrenaline shows the pronounced adaptogenic effect of the concentrate, whereas phytoecdysteroids and flavonoids act as prostressors activating body antioxidant protection system, what is substantiated by significantly increased blood superoxide dismutase level of experimental animals.

Pathogenetic treatment of patients with hypertension depending on the level of sympathоadrenal system activity

Purpose of the study. Recently, new opportunities to optimize clinical efficacy and tolerability of treatment of patients with essential hypertension appeared. Determination of the indicators of increased activity of the sympathetic nervous system (SNS) in practice could contribute to differentiated treatment of patients with hypertension. Comparative estimation of influence of complex treatment with bisoprolol or amlodipine on the SNS activity parameters in patients with arterial hypertension (AH) of II stage.&#x0D; Materials and methods. 121 patients (men and women) with documented II stage AH were examined clinically. Concentrations of adrenaline, noradrenaline, dopamine and DOPA in urine were evaluated by spectrochromatography, endotheliumdependent vasodilation was studied using complex rheographic ReoCom Professional (HAI-Medicom, Ukraine). Patients were divided into 2 groups: if concentration of noradrenalin in urine exceeds healthy subjects levels more than on 20% – patients were added to basic treatment (enalapril, atorvastatin, aspirin) bisoprolol, if concentration of noradrenalin in urine exceeds healthy subjects levels less than on 20% – we added amlodipine. Statistic analysis was done on Apache OpenOffice (version 4.1) and PSPP (version 0.7.9).&#x0D; Results. The study showed that after treatment there was significant decrease of adrenalin, noradrenalin in 1st group . Increase of DOPA levels was higher in 1st group (Δ% = +46,5 [30,0; 55,4]% vs Δ% = +8,8 [–2,1 ; 16,0]%, (p &lt; 0,05).). Trends in daily urinary excretion of adrenaline (–44,8%) and norepinephrine (–33,7%) showed the impact of effective Δ-blocker on the activity of pressor systems. DOPA excretion was increased significantly in both groups which can indirectly indicate hemodynamic load reduction in hypertensive patients. When choosing the individual antihypertensive treatment in patients with arterial hypertension, if excretion of noradrenalin is increased it is rationally to add adjuvant therapy with β-blockers.&#x0D; Conclusion. The results of our research can be applied into the practice of general practitioner as recommendations for individual selection of antihypertensive treatment depending on the activity of sympathetic nervous system.

Activation of the Sympathetic Nervous System Promotes Blood Pressure Salt-Sensitivity in C57BL6/J Mice.

Global salt intake averages >8 g/person per day, over twice the limit advocated by the American Heart Association. Dietary salt excess leads to hypertension, and this partly mediates its poor health outcomes. In ≈30% of people, the hypertensive response to salt is exaggerated. This salt-sensitivity increases cardiovascular risk. Mechanistic cardiovascular research relies heavily on rodent models and the C57BL6/J mouse is the most widely used reference strain. We examined the effects of high salt intake on blood pressure, renal, and vascular function in the most commonly used and commercially available C57BL6/J mouse strain. Changing from control (0.3% Na+) to high salt (3% Na+) diet increased systolic blood pressure in male mice by ≈10 mm Hg within 4 days of dietary switch. This hypertensive response was maintained over the 3-week study period. Returning to control diet gradually reduced blood pressure back to baseline. High-salt diet caused a rapid and sustained downregulation in mRNA encoding renal NHE3 (sodium-hydrogen-exchanger 3) and EnaC (epithelial sodium channel), although we did not observe a suppression in aldosterone until ≈7 days. During the development of salt-sensitivity, the acute pressure natriuresis relationship was augmented and neutral sodium balance was maintained throughout. High-salt diet increased ex vivo sensitivity of the renal artery to phenylephrine and increased urinary excretion of adrenaline, but not noradrenaline. The acute blood pressure-depressor effect of hexamethonium, a ganglionic blocker, was enhanced by high salt. Salt-sensitivity in commercially sourced C57BL6/J mice is attributable to sympathetic overactivity, increased adrenaline, and enhanced vascular sensitivity to alpha-adrenoreceptor activation and not sodium retention or attenuation of the acute pressure natriuresis response.

A long-term perspective on cardiovascular job stress research.

This review provides perspectives on cardiovascular occupational stress research since the 1960s until now. The author argues for closer links between basic science and clinical follow‐up examinations of patients. In an excellent way urinary excretion of adrenaline and noradrenaline during wake hours mirrors day to day or week to week variations in sympathomedullary activity which could be related to variations in the patient's and cardiovascular and psychosocial situation. Modern methods for following variations over time in heart contractility should also be related to the patients' psychosocial situation. In addition the author argues for more extensive use of the increasing knowledge regarding regeneration and vagal activity in relation to variations in job conditions and development or prevention of cardiovascular disease.

Affective disorders on the&#x0D; background of hypothyroidism.

Introduction. Affective disorders are the most common psychopathological symptoms of hypothyroidism. Hypothyroidism greatly reduces the effectiveness of antidepressants and replacement L-thyroxine therapy is not enough to eliminate the anxiety and depressive disorders in hypothyroidism. Aim. The purpose of the research is study of psychosomatic and somatopsychical relationships in hypothyroidism and depression. Material and methods. Four hundred and six patients (78 men and 328 women) with affective disorders aged 51,3 ± 4,7 years were examined. The concentration of thyroid-stimulating hormone (TSH), thyroxine (T4), cortisol, adrenocorticotropic hormone (ACTH) in the blood, urinary excretion of norepinephrine and epinephrine was determined. Severity of depression was estimated by the Hamilton Depression Rating Scale (HDRS), alexithymia level - by the Toronto alexithymia scale (TAS-26). Results. In euthyroid patients TSH level was 2,7 ± 0,13 mU/l, in hypothyroid - 14,1 ± 1,21 mU / l (p&lt;0.001), T4 level was 14,4 ± 1,36 and 7.1±1.16 pmol/l, respectively (p&lt;0.001). Depressive disorders were revealed in 374 patients (92.1%), other affective disorders - in 32 patients (7.9%). Hypothyroid patients had more pronounced depression by the Hamilton Rating Scale for Depression and a higher average score by TAS-26 as compared to euthyroid patients (17,8 ± 2,1 vs 15,3 ± 1,9 points, p=0.001and 79,9 ± 4,6 vs. 71,1 ± 4,4 points; p&lt;0.001 respectively). TSH level has a direct correlation with severity of depression (R=0,62; р&lt;0,001). Severe depression was observed in hypothyroid patients more often than in euthyroid patients (9.5% vs. 5.0%; р=0,029). Patients with affective disorders and hypothyroidism have a higher cortisol level and lower ACTH level than euthyroid patients (503±12.1 vs. 420±10.9 nmol/l; р&lt;0.001 and 12.9±3.07 vs. 15.3±3.4; р&lt;0.001 respectively). Urinary excretion of epinephrine and norepinephrine in hypothyroid patients was higher than that in euthyroid patients: 37,8 ± 2,18 vs. 31,1 ± 2,06 nmol (p&lt;0.001) and 39,2 ± 2,14 vs. 33,4 ± 2,1 nmol (p&lt;0.001), respectively. Conclusions. Prevalence of hypothyroidism among patients with affective disorders is higher than in the general population. The severity of the depression has a direct correlation with TSH. Activity of the sympathetic division of the autonomic nervous system is higher in patients with hypothyroidism than in patients with euthyroidism.

Emotional stress and stress-regulating systems indicators in children and adolescents from the Joint forces operation zone

Objective — to assess indicators of stress-regulating systems in children of school age from the Joint forces operation (JFO) zone, depending on the presence or absence of stress.Materials and methods. 129 children and adolescents of both sexes aged 7 to 17 years from the JFO zone, including 54 migrant peers, have been examined by us. We researched the state of stress-realizing (cortisol, TBA-active products, diene conjugates, adrenaline, noradrenaline) and stress-limiting (serotonin, melatonin, reduced glutathione, glutathione peroxidase (GPO), superoxide dismutase) systems.Results and discussion. In presence of stress there is a verifiable increase of cortisol concentration in children and adolescents from the JFO zone and in migrants, when compared to adolescents without stress. We have identified in adolescent migrants a decrease of GPO activity and an increase of melatonin level in presence of stress. In absence of stress there is in adolescents from the JFO zone a noted decrease in level of urinary excretion of adrenaline. In migrants we have identified a reverse tendency.Conclusions. In children and adolescents from the JFO zone and in migrants we have established differences in nature of changes in stress-regulating systems, which point to pathogenic peculiarities in development of mechanisms of adaptation to undergone stress.

The effects of age and ethnicity on the circadian variation of catecholamines and cortisol in employed women

BackgroundWomen employed outside the home in urban settings must adapt to changing circadian microenvironments. The pattern and extent of vasoactive hormone responses to these changes may depend upon age and ethnic background. The purpose of this study was to evaluate the effects of age and ethnicity on the circadian variation of urinary norepinephrine, epinephrine, and cortisol excretion across work, home and sleep microenvironments.MethodsThe subjects of the study were 95 women (38 European-American, age = 35.4 ± 7.4; 28 African-American, age = 33.4 ± 7.9; 12 Asian-American, age = 36.7 ± 9.3 and 17 Hispanic-American age = 31.6 ± 10.9) employed as secretaries, lab technicians or office supervisors in New York City. Variation in the hormones across the microenvironments was evaluated using repeated measures ANCOVA with age group (18–29.9; 30–39.9; 40–49.9) and ethnicity as fixed factors.ResultsThe results show that for norepinephrine and epinephrine, work excretion rates are substantially higher than sleep rates (p < .001), and for epinephrine home rates were higher than sleep rates (p < .001). Work and sleep cortisol excretion rates were also significantly higher than the rate at home, consistent with cortisol’s circadian rhythm. (p < .002). Women in their twenties had substantially lower norepinephrine excretion rates than women over 30 (p < .04). There were also ethnic differences in norepinephrine (p < .04) and epinephrine (p = .11) output with Asian-American women having the lowest and African-American women having the highest rates. This variation is likely related to the ethnic variation in weight. There was no significant variation in cortisol excretion with age or ethnicity.ConclusionThe circadian rates of norepinephrine excretion differ by age and that of both catecholamines differ by ethnicity among women working outside the home. It is speculated that the age variation in norepinephrine may contribute to the development of vasomotor symptoms.

Diurnal variations of heart rate, urine flow and catecholamine excretion in subjects wearing clothing that provides different thermal insulation

This study investigated the effects of clothing providing different Clo values upon the circadian rhythm of sympathetic nervous activity, as inferred from urinary catecholamine excretion and heart rate, in a thermoneutral environment. Seven health female subjects were studied for 37.5 h, from 21:00 h on the first day to 10:30 h on the third day, in an isolated climatic chamber controlled at 23.8 ± 0.2 °C and 60 ± 5% RH. Light intensity was 500 lux from 06:30 to 19:30 h, 100 lux from 19:30 to 22:30 h and 0 lux from 22:30 to 06:30 h. Subjects were tested while wearing two different types of clothing: Type L, offering 1.048 Clo of thermal insulation and with the subjects’ extremities covered; and Type H, 0.744 Clo of thermal insulation and the subjects’ extremities exposed. Urine samples were collected every 4 h, their volumes were measured and they were later assayed for their contents of adrenaline and noradrenaline; the mean heart rate for each of these 4-h periods was also calculated. The daily profiles of the variables were assessed by ANOVA, which indicated that the amplitudes and phases of the daily rhythms differed between the clothing types. This result was examined in more detail by assessing the profiles by single and group cosinor analysis (period = 24 h). All four physiological variables showed clear and statistically significant group cosinor rhythms with both types of clothing. The mean amplitudes of urine flow, the excretion rate of urinary adrenaline and heart rate were greater when wearing Type H rather than Type L clothing (p = 0.01 for urine flow and heart rate; p = 0.072 for rate of excretion of adrenaline). Also, the acrophase of the rate of urinary adrenaline excretion was earlier in all subjects wearing Type H rather than Type L clothing (p = 0.048), and the acrophases of urine flow and urinary noradrenaline excretion rate were earlier in six and five of the subjects, respectively. These results show that clothing which is worn in an environment of moderate temperature (23.8 °C) and which offers a lower Clo value (especially if the distal extremities are exposed) might induce an increase in amplitude and/or an advance of acrophase in circadian rhythms of urine flow, excretion of urinary catecholamines and heart rate. It is suggested that these rhythmic changes, which imply changes in the daily profile of sympathetic nervous system activity, might be important when daily thermoregulation and comfort in response to the type of clothing being worn in daily life are considered.

Circadian misalignment increases cardiovascular disease risk factors in humans

Shift work is a risk factor for hypertension, inflammation, and cardiovascular disease. This increased risk cannot be fully explained by classic risk factors. One of the key features of shift workers is that their behavioral and environmental cycles are typically misaligned relative to their endogenous circadian system. However, there is little information on the impact of acute circadian misalignment on cardiovascular disease risk in humans. Here we show-by using two 8-d laboratory protocols-that short-term circadian misalignment (12-h inverted behavioral and environmental cycles for three days) adversely affects cardiovascular risk factors in healthy adults. Circadian misalignment increased 24-h systolic blood pressure (SBP) and diastolic blood pressure (DBP) by 3.0 mmHg and 1.5 mmHg, respectively. These results were primarily explained by an increase in blood pressure during sleep opportunities (SBP, +5.6 mmHg; DBP, +1.9 mmHg) and, to a lesser extent, by raised blood pressure during wake periods (SBP, +1.6 mmHg; DBP, +1.4 mmHg). Circadian misalignment decreased wake cardiac vagal modulation by 8-15%, as determined by heart rate variability analysis, and decreased 24-h urinary epinephrine excretion rate by 7%, without a significant effect on 24-h urinary norepinephrine excretion rate. Circadian misalignment increased 24-h serum interleukin-6, C-reactive protein, resistin, and tumor necrosis factor-α levels by 3-29%. We demonstrate that circadian misalignment per se increases blood pressure and inflammatory markers. Our findings may help explain why shift work increases hypertension, inflammation, and cardiovascular disease risk.

Effects of softness of bedding materials upon overnight excretion of urinary catecholamines and sleep quality in warm environmental conditions

The purpose of this study was to investigate whether, when subjects were living in a moderately warm environment: (1) the softness of clothing worn during the daytime could influence the subjects’ preference in the evening for the softness of clothing and a face towel; and (2) the softness of bedding materials could modulate their nocturnal body temperature, overnight urinary catecholamine excretion, and sleep quality. Six females were tested during the luteal phase of their menstrual cycles. The experiment was conducted over three consecutive days and nights in a climatic chamber controlled at 28 ± 0.2 °C and 50% RH during the evening (from 19:30 to 21:30 h) and at 29 ± 0.2 °C and 50% RH during the sleep period (from 22:30 to 07:00 h). The first night was for adaptation to the experimental chamber. Five different sets of clothing and bedding were used; these were identical except for the softness/hardness of the materials used (due to treatment with fabric softener or starch), and material softness decreased in the order: Type A (softest) > Type B > Type C > Type D > Type E (hardest). There were two phases to the experiment, conducted in random order. In one phase, subjects wore “soft type” (Type B) T-shirt and shorts in the daytime and, in the other phase, “hard type” (Type D/E) T-shirt and shorts. In both phases, subjects were asked at 21:30 h to select a T-shirt and a face towel which they felt would be most comfortable to use. At night, they slept on bedding (a mattress cover, a pillowcase and a covering blanket) which was of the same degree of softness as the T-shirt and shorts that had been worn in the daytime in that phase. Rectal temperature, skin temperatures at seven sites, and body movement were measured during sleep, an overnight urine sample was taken for measurement of urinary excretion of adrenaline and noradrenaline, and subjective sleep quality was assessed on being woken the following morning. The main results were as follows: (1) T-shirt preference in the evening showed large inter-individual variation but did not differ significantly between the two phases (when “hard type” or “soft type” clothing had been worn during the daytime). The preferred texture of the face towel was softer than that of the T-shirt, the difference in softness between the chosen face towel and T-shirt being significant (p < 0.05 and p < 0.10, respectively, when having worn “soft type” and “hard type” clothing in the daytime). (2) Rectal temperature and mean skin temperature were not significantly different when sleeping with “soft type” (Type B) and “hard type” (Type D/E) bedding materials. (3) Overnight secretions of urinary adrenaline and noradrenaline were significantly less with “soft type” than “hard type” (p < 0.01 and p < 0.05 for adrenaline and noradrenaline, respectively) bedding. (4) When sleeping with “soft type” bedding materials, five out of the six subjects showed less body movements during the sleep period and reported that they had slept better. These results suggest that, in a moderately warm environment, bedding materials with a softer texture might be more comfortable to the subject (due to less tactile stimulation of the skin, which results in neurophysiological relaxation) and provide them with better sleep quality.

Increased Nitrogen Retention after Trans-Operative Intravenous Amino Acid and Glucose Infusion, without Changes in Urinary Amino Acid, Adrenaline and Plasma Urea or Glucose

Objective: Nutritional deficiencies are associated with increased morbidity and mortality during and after surgery. The present study evaluated nitrogen retention after transoperative intravenous infusion of amino acids and glucose. Design: Prospective study. Setting: Large community hospital. Patients: 18 randomly chosen patients undergoing medium or major surgeries. Interventions and Measurements: The experimental design included a 12-hour period before surgery (P1), a trans-operative period of 6 hours (P2), an early postoperative period (P3, 18 hours), and a late postoperative period (P4, 24 hours). Urinary amino acid and nitrogen were analyzed from P1 through P4. Group I, nine patients, received Ringer’s lactate solution with 5% glucose, and Group II, another nine patients, received a 6.6% amino acid and 16.6% glucose solution over a 6-hour trans-operative period (P2) starting from the anesthesia procedures. All surgical procedures lasted a maximum of 3 hours. Results: There was no statistically significant difference in urinary amino acid or adrenaline excretion between P1 and P4 in either group. Nitrogen excretion values were also similar for both groups, i.e., 0.39 ± 0.16 and 0.39 ± 0.28 g/hour, respectively. The nitrogen balance showed greater nitrogen retention (﹣0.25 ± 0.24 g/hour) in the group receiving the amino acid infusion compared to the group receiving Ringer’s lactate solution (﹣0.59 ± 0.26 g/hour) (P < 0.05). Blood plasma urea nitrogen and glycaemia did not increase at the end of the study (P4 period) in either group. Conclusion: These data indicate that trans-operative infusion of glucose and amino acids can be beneficial for patients submitted to surgical stress in terms of nitrogen retention.

Deep brain stimulation for obsessive–compulsive disorder is associated with cortisol changes

Deep brain stimulation (DBS) is an effective treatment for obsessive-compulsive disorder (OCD), but its mechanism of action is largely unknown. Since DBS may induce rapid symptomatic changes and the pathophysiology of OCD has been linked to the hypothalamic-pituitary-adrenal (HPA) axis, we set out to study whether DBS affects the HPA axis in OCD patients. We compared a stimulation ON and OFF condition with a one-week interval in 16 therapy-refractory OCD patients, treated with DBS for at least one year, targeted at the nucleus accumbens (NAc). We measured changes in 24-h urinary excretion of free cortisol (UFC), adrenaline and noradrenaline and changes in obsessive-compulsive (Y-BOCS), depressive (HAM-D) and anxiety (HAM-A) symptom scores. Median UFC levels increased with 53% in the OFF condition (from 93 to 143nmol/24h, p=0.12). There were no changes in urinary adrenaline or noradrenaline excretion. The increase in Y-BOCS (39%), and HAM-D (78%) scores correlated strongly with increased UFC levels in the OFF condition. Our findings indicate that symptom changes following DBS for OCD patients are associated with changes in UFC levels.

Preliminary Study of Urinary Catecholamines in Hypertension

Introduction: Clinical manifestations in some patients suffering from essential hypertension are suggestive of sympathetic nor adrenaline (NAD) d e - termination is that the increased activity of the. Sympathetic nervous system in hypertension, if any, .is associated with a greater release of NAD. Into the blood, followed by an increase in its metabolism and excretion. Taking into the view of this controversy in results preliminary investigations of the level of catecholamines in hypertensive patients, have been taken. Material and Methods: Collection of 24 hr. urine specimen was done at pH 4 to inhibit the oxidation of catecholamines by using approximately 5 ml of H2S04 of 3 mol/Lit. This acidified urine was refrigerated at 4°C for the storage purposes and analysed when required. After 20—30 minutes the fluorescence of the resulting products was read with JASCO-550 Spectrofluormeter, at 385 mu(excitantion) and 485 mu(emission) wavelength for nor-adrenaline and at 410 mu(excitation) and 490 mu(emission) for adrenaline. Results : During this study, 20 hypertensive patients and 10 nor ostensive subjects were evaluated for the catecholamine contents in urine. The data of these subjects is given in Table-i (hypertensives) and Table-2) (normotensives). Other parameters such as age, systolic and diastolic blood pressure when corr pared in hypert ensive patients with normotensive subjects except age other two parameters were found satisfically significant (< .001 and < .01 respectively). Discussion: In present studies when CA ‘s were compared between hypertensive patients and normotensive subjects, the mean value of CA’s in normotensives was found more than hypertensive patients, though it was not satistically significant (Table-3). These findings confirmed the results of D’Amelio, et al. (1978). They reported “no significant differences were noted in urinary excretion of adrenaline and noradrenaline in standardized basal conditions among normal and hypertensive (essential and renovascular) patients. It seems that if there would have not been in any medication the values of CAS might have been higher in hypertensive patients than controls.

Urinary Excretion of Epinephrine and Dopamine Correlates with Efficiency of G-CSF Mobilized Stem Cells in Patients with Al Amyloidosis

Urinary Excretion of Epinephrine and Dopamine Correlates with Efficiency of G-CSF Mobilized Stem Cells in Patients with Al Amyloidosis

Urinary Excretion of Epinephrine and Dopamine Correlates with Efficiency of G-CSF Mobilized Stem Cells in Patients with AL Amyloidosis

Abstract 316 Introduction:Hematopoietic stem cell migration out of the bone marrow is essential for effective and successful stem cell transplantation. Sympathetic nervous system signaling has been shown to regulate hematopoietic stem cell egress from bone marrow. Ablation of adrenergic neurotransmission in animal models indicates that norepinephrine signaling controls granulocyte colony stimulating factor (G-CSF) -induced osteoblast suppression, CXCL-12 (or stromal derived factor-1 (SDF-1)) down regulation and hematopoietic progenitor cell mobilization (Katayama Y, et al. Cell 2006). In addition, β adrenergic agonists and antagonists enhance and reduce stem cell mobilization, respectively. High dose therapy and stem cell rescue following G-CSF mobilization is a standard approach to the treatment of patients with light chain (AL) amyloidosis. In patients with AL amyloidosis, we prospectively studied the relationship between catecholamine levels and the efficiency of stem cell collection. Methods: In AL amyloidosis patients enrolled on a phase II clinical trial using G-CSF mobilization and high dose melphalan conditioning, 24 h urine samples were collected and analyzed for epinephrine, norepinephrine and dopamine excretion before G-CSF administration and after stem cell collection was completed. Statistical analysis included the Spearman Rank Coefficient (r), Wilcoxon Rank Sum test and Signed rank test. Results: In 39 patients with AL Amyloidosis collected on study, median CD34+ cells collected per kg was 8.3 × 106 (IQR 5,12.3) in a median of 2 (IQR 2,3) collections. The median number of CD34+ cells infused on day 0 was 4.7 × 106 (IQR 3.8, 6) per kg and time to neutrophil engraftment (ANC > 500 × 2 days) was 9 (IQR 9, 11) days. Baseline urinary excretion of epinephrine and dopamine correlated with total number of CD34+ cells per kg collected (r = 0.33, P = 0.005; and r = 0.47, P = 0.05, respectively). An optimal collection outcome defined as > 5 × 106CD34+ cells in 2 collections was achieved by 25/39 patients and was associated with higher baseline epinephrine (median 7 versus 4mcg/24h, P = 0.02) and dopamine (median 220 versus 156mcg/24h, P = 0.05) but not norepinephrine levels. When comparing baseline and post collection catecholamine levels, only dopamine values changed significantly from before to after stem cell collection (P = <0.0001). Patients with renal involvement as the only site of disease (N= 16) collected greater total CD34+ stem cells per kg (median 11.4 versus 6, P = 0.002) than patients with other sites or more than one site of disease (N=23). There was no correlation between the number of stem cells infused and the time to engraftment. Conclusion: Consistent with the notion that the sympathetic nervous system regulates the egress of progenitor cells from their niche, we found that baseline epinephrine and dopamine excretion is associated with greater total and more efficiently collected CD34+ stem cells following G-CSF mobilization in patients with AL amyloidosis. In mouse models G-CSF-induced mobilization requires peripheral adrenergic signals and reduces norepinephrine in the bone (Katayama Y, et al. Cell 2006). Reduced dopamine excretion following G-CSF administration in this study may indicate that circulating catecholamines may provide a marker for the overall sympathetic tone that could predict mobilization efficiency in humans. Further, this study supports other results on the role of dopamine in progenitor migration (Spiegel A, et al. Nat Immunol. 2007) and suggests an important role of dopamine in G-CSF-induced mobilization in patients with AL amyloidosis. Together, these data suggest that modulation of the sympathetic nervous system to enhance hematopoietic stem cell mobilization should be explored and that approaches such as the one we describe may guide G-CSF mobilization with respect to the need for Plerixafor. Disclosures:No relevant conflicts of interest to declare.

Effects of Skin Pressure from Compression Legwear on Resting Salivary Cortisol and Urinary Catecholamines Excretion in Women

The benefits of compression legwear (CL) have been demonstrated in the improvement of vascular function and venous return of the lower extremities, but their effect on autonomic nervous system (ANS) activities and human stress response remain controversial. To investigate the possible effects of CLs on ANS activities and in inducing stress on the human body. Resting salivary cortisol and urinary catecholamine (adrenaline and noradrenaline) excretions were examined in 12 healthy women. The effects of different skin pressure levels exerted by CL were studied by conducting a 4-hour prolonged standing and sitting wear trial with intermittent sampling of the aforementioned biochemical parameters. No statistically significant differences in resting salivary cortisol and urinary catecholamines were found between control and different clothing pressure conditions (light, mild, moderate, and strong), although the secretion of salivary cortisol (SSC) showed a significant decrease during the 180minutes of the testing period that was maintained up to 10minutes after the CL was removed for the studied pressure conditions. Urinary excretion of adrenaline and noradrenaline decreased with increasing pressure levels and was lower in response to higher clothing pressure when tested in the afternoon. Constant pressure exerted by CL did not cause any stimulation of the sympathetic nervous system. The prolonged wearing of CL while standing or sitting did not induce any stress on the human body, suggesting that CL can be safely used in the treatment of patients with venous disorders of the lower extremities.

Plasma chromogranin A levels are increased in a small portion of patients with hereditary head and neck paragangliomas

The majority of patients with head and neck paragangliomas (HNPGL) have biochemically silent tumours. Chromogranin A (CgA) is a tumour marker for neuroendocrine tumours. To assess the role of CgA as a tumour marker in patients with hereditary HNPGL. We included 95 consecutive patients with hereditary HNPGL for screening of plasma CgA levels and catecholamine excess by measurement of 24-h urinary excretion of (nor)metanephrine, (nor)adrenaline, VMA, dopamine and 3-methoxytyramine. In all patients with catecholamine excess, abdominal/intrathoracic paragangliomas were excluded by (123) I-MIBG scintigraphy, MRI and/or CT. Plasma CgA levels were increased in only 15 of 95 patients (16%). Thirty-three of the 95 patients (35%) had increased urinary excretion rates of catecholamines. Six of these 33 patients (18%) had increased plasma CgA levels. Nine of the 62 patients (15%) with a biochemically silent tumour, i.e. no increased urinary excretion of catecholamines or their metabolites, had increased CgA levels. Increased plasma CgA levels were positively correlated with urinary excretion rates of noradrenaline (r = 0·68, P = 0·005) and normetanephrine (r = 0·68, P = 0·005). There was a positive correlation between maximal HNPGL diameter and plasma CgA levels in the 57 patients with a single HNPGL (r = 0·57, P = 0·001). Plasma CgA levels are increased in only a small portion of patients with hereditary HNPGL and have limited additional value to the combination of radiological and routine biochemical assessment of patients with HNPGL. Increased plasma CgA levels are associated with increased noradrenergic activity and tumour size in patients with a single HNPGL.