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Background: Studying biomarkers in children with temporomandibular disorders (TMD) such as epinephrine, norepinephrine, and dopamine may reveal factors like screen time or sleep loss that affect these biomarkers and predict TMD-related pain, offering new research opportunities., Aim: To determine the association between stress and catecholamines with myofascial pain and headache related to TMD in children., Design: Sixty-six 9- to 11-year-old children assisting at the clinics of Pediatric Dentistry of Universidad CES participated in the study. Myofascial pain and headache attributed to TMD were determined according to the Diagnostic Criteria for TMD (DC/TMD) Axis I. Stress was evaluated with the Perceived Stress Scale-Children (PSS-C), and a 24-h urine sample was analyzed using liquid chromatography to assay catecholamines. Single and multiple regression analyses were performed., Results: Children with a mean age of 10.3 years participated in the study. The mean score of stress was 29 ± 4. Perceived stress, dopamine, epinephrine, and norepinephrine were statistically significant predictors of myofascial pain and headache attributed to TMD in the single- and multiple variable logistic regression analyses., Conclusion: Stressful states and its biological biomarkers increase the probability of developing myofascial pain and headache attributed to TMD in children., (© 2024 BSPD, IAPD and John Wiley & Sons Ltd.)

Background: Amphiregulin (AREG) is a growth factor linked to cardioprotection and heart pathology during myocardial stress. Our aim was to investigate cardiac AREG expression, its potential as a postmortem hypothermia marker and its possible stress hormone dependency in different types of deaths., Materials and Methods: Heart RNA was isolated from hypothermic, cardiac and non-cardiac deaths. Relative AREG mRNA levels and urine stress hormone concentrations were measured by qPCR and enzyme-linked immunosorbent assays from eight different death cause groups. Receiver operating characteristic curve was used to evaluate a cut-off point for AREG expression as a hypothermia marker. Regulatory elements were predicted by PROMO., Results: The AREG mRNA levels were significantly higher in hypothermic deaths than in most cardiac and non-cardiac deaths. AREG expression indicated hypothermic deaths with nearly 70% sensitivity and specificity. However, high expression levels were also detected in non-ischaemic deaths. The highest concentrations of adrenaline and cortisol were detected in hypothermic deaths, while the highest noradrenaline concentrations associated with atherosclerotic heart disease (AHD) deaths with acute myocardial infarction and trauma deaths. There were no significant correlations between stress hormones and AREG mRNA in hypothermic and non-cardiac deaths, whereas moderate-to-high associations were detected in cardiac deaths. Putative response elements for cortisol and catecholamines were found in AREG ., Conclusions: Severe hypothermia activates cardiac AREG expression practicable as a postmortem hypothermia marker. Cortisol and catecholamines may act as transcriptional modifiers of this gene, especially in long-term ischaemic heart disease. However, the exact role of these hormones in upregulation of AREG during hypothermia remains unclear.

Objective: Mean arterial pressure (MAP) plays a significant role in regulating tissue perfusion and urine output (UO). The optimal MAP target in critically ill patients remains a subject of debate. We aimed to explore the relationship between MAP and UO., Design: A retrospective observational study., Setting: A general ICU in a tertiary medical center., Patients: All critically ill patients admitted to the ICU for more than 10 hours., Interventions: None., Measurements and Main Results: MAP values and hourly UO were collected in 5,207 patients. MAP levels were categorized into 10 groups of 5 mm Hg (from MAP < 60 mm Hg to MAP > 100 mg Hg), and 656,423 coupled hourly mean MAP and UO measurements were analyzed. Additionally, we compared the UO of individual patients in each MAP group with or without norepinephrine (NE) support or diuretics, as well as in patients with acute kidney injury (AKI).Hourly UO rose incrementally between MAP values of 65-100 mm Hg. Among 2,226 patients treated with NE infusion, mean UO was significantly lower in the MAP less than 60 mm Hg group (53.4 mL/hr; 95% CI, 49.3-57.5) compared with all other groups (p < 0.001), but no differences were found between groups of 75 less than or equal to MAP. Among 2500 patients with AKI, there was a linear increase in average UO from the MAP less than 60 mm Hg group (57.1 mL/hr; 95% CI, 54.2-60.0) to the group with MAP greater than or equal to 100 mm Hg (89.4 mL/hr; 95% CI, 85.7-93.1). When MAP was greater than or equal to 65 mm Hg, we observed a statistically significant trend of increased UO in periods without NE infusion., Conclusions: Our analysis revealed a linear correlation between MAP and UO within the range of 65-100 mm Hg, also observed in the subgroup of patients treated with NE or diuretics and in those with AKI. These findings highlight the importance of tissue perfusion to the maintenance of diuresis and achieving adequate fluid balance in critically ill patients., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine.)

Introduction and Objectives: Hepatorenal syndrome (HRS) is a serious complication of cirrhosis treated with various medications. We aim to evaluate terlipressin and albumin's effectiveness and safety compared to albumin and noradrenaline in adult hepatorenal disease patients., Materials and Methods: Clinical trials from four databases were included. Cochrane's approach for calculating bias risk was utilized. We rated the quality evaluation by Grading of Recommendations Assessment, Development, and Evaluation (GRADE). We included the following outcomes: serum creatinine (mg/dl), urine output (ml/24 h), mean arterial pressure (mmHg), reversal rate of HRS, mortality rate, blood plasma renin activity (ng/ml/h), plasma aldosterone concentration (pg/ml), urine sodium (mEq/l), and creatinine clearance (ml/min)., Results: Our analysis of nine clinical studies revealed that the noradrenaline group was associated with higher creatinine clearance (MD = 4.22 [0.40, 8.05]), (P = 0.03). There were no significant differences in serum creatinine levels (MD = 0.03 [-0.07, 0.13]), urinary sodium (MD = -1.02 [-5.15, 3.11]), urine output (MD = 32.75 [-93.94, 159.44]), mean arterial pressure (MD = 1.40 [-1.17, 3.96]), plasma renin activity (MD = 1.35 [-0.17, 2.87]), plasma aldosterone concentration (MD = 55.35 [-24.59, 135.29]), reversal rate of HRS (RR = 1.15 [0.96, 1.37]), or mortality rate (RR = 0.87 [0.74, 1.01]) between the two groups (p-values > 0.05)., Conclusions: Noradrenaline is a safe alternative medical therapy for HRS., Competing Interests: Declaration of interests None., (Copyright © 2024 Fundación Clínica Médica Sur, A.C. Published by Elsevier España, S.L.U. All rights reserved.)

Twenty-four-hour urine measurements play a crucial role in the diagnosis, follow-up and treatment of various diseases. There are different approaches to the collection of urine in patients who need to collect multiple urine samples at a time, especially in hospitals with heavy workloads. In this study, we compared the sodium, potassium, chloride, amylase, calcium, creatinine, phosphorus, microalbumin, protein, magnesium, urea, uric acid, adrenaline, noradrenaline, dopamine, metanephrine, normetanephrine, vanillylmandelic acid, 5-hydroxyindoleacetic acid and homovanillic acid results of 24-h urine samples analyzed immediately without acid addition, which we accepted as the reference and baseline measurement, with the results of the samples analyzed after waiting for 24 h without acid addition, analyzed immediately with acid addition and analyzed after waiting for 24 h with acid addition. Chloride, microalbumin, amylase and protein tests, which are recommended to be measured in the sample without preservatives, are affected by acid addition. Adrenaline, noradrenaline and dopamine, which are the tests recommended to be measured in acid-added urine are degraded in the samples without acid, and the levels of metanephrine and normetanephrine were not significantly degraded in the absence of preservatives.

Urinary catecholamines (CAs) have been examined for the screening of pheochromocytomas. The decision to perform screening is based on symptoms suggesting secondary hypertension or hyperactivities of the sympathetic nervous system. To elucidate the usefulness of urinary fractions and ratios of CAs, 79 patients in whom 24-h excretions of urinary CAs including adrenaline (AD), noradrenaline (NA) and dopamine (DA) had been examined from 2015 until 2020 were retrospectively analyzed. There were no significant differences in urinary CA levels between two age groups, gender groups and two BMI groups. Patients with histories of preexisting hypertension and diabetes showed significantly higher levels of urinary NA excretion, and the urinary ratio of NA/DA was also increased in the patients with a history of hypertension. Heart rate (HR) was significantly correlated with the urinary ratio of NA/DA. Serum free thyroxine (FT4) concentration and ratio of FT4/thyrotropin (TSH) were correlated with the level of urinary AD. The levels of TSH and FT4/TSH showed negative and positive correlations, respectively, with the urinary NA/DA ratio. Thus, increases of HR are related to the enhanced conversion of DA to NA and increased thyroid hormones are involved in the increase in urinary AD and the conversion of DA to NA. History of lifestyle-related diseases and changes of HR and thyroid functions need to be considered for the evaluation of urinary CAs and their ratios.

Short sleep duration and poor sleep quality are associated with cardiovascular risk, and sympathetic nervous system (SNS) dysfunction appears to be a key contributor. The present review will characterize sympathetic function across several sleep disorders and insufficiencies in humans, including sleep deprivation, insomnia, narcolepsy, and obstructive sleep apnea (OSA). We will focus on direct assessments of sympathetic activation, e.g., plasma norepinephrine and muscle sympathetic nerve activity, but include heart rate variability (HRV) when direct assessments are lacking. The review also highlights sex as a key biological variable. Experimental models of total sleep deprivation and sleep restriction are converging to support several epidemiological studies reporting an association between short sleep duration and hypertension, especially in women. A systemic increase of SNS activity via plasma norepinephrine is present with insomnia and has also been confirmed with direct, regionally specific evidence from microneurographic studies. Narcolepsy is characterized by autonomic dysfunction via both HRV and microneurographic studies but with opposing conclusions regarding SNS activation. Robust sympathoexcitation is well documented in OSA and is related to baroreflex and chemoreflex dysfunction. Treatment of OSA with continuous positive airway pressure results in sympathoinhibition. In summary, sleep disorders and insufficiencies are often characterized by sympathoexcitation and/or sympathetic/baroreflex dysfunction, with several studies suggesting women may be at heightened risk.

Pheochromocytoma (Pheo) is a tumor derived from chromaffin cells. It can be studied using 18F-dihydroxyphenylalanine (DOPA)-positron emission tomography (PET) due to its overexpression of L-type amino acid transporters (LAT1 and LAT2). The oncogenic pathways involved are still poorly understood. This study examined the relationship between 18 F-DOPA-PET uptake and LAT1 expression, and we explored the role of miR-375 and putative target genes. A consecutive series of 58 Pheo patients were retrospectively analyzed, performing 18 F-DOPA-PET in 32/58 patients. Real-time quantitative PCR was used to assess the expression of LAT1, LAT2, phenylethanolamine N-methyltransferase (PNMT), miR-375, and the major components of the Hippo and Wingless/Integrated pathways. Principal germline mutations associated with hereditary Pheo were also studied. Pheo tissues had significantly higher LAT1, LAT2, and PNMT mRNA levels than normal adrenal tissues. MiR-375 was strongly overexpressed. Yes-associated protein 1 and tankyrase 1 were upregulated, while beta-catenin, axin2, monocarboxylate transporter 8, and Frizzled 8 were downregulated. A positive relationship was found between 18 F-DOPA-PET SUV mean and LAT1 gene expression and for 24 h-urinary norepinephrine and LAT1. This is the first experimental evidence of 18 F-DOPA uptake correlating with LAT1 overexpression. We also demonstrated miR-375 overexpression and downregulated (Wnt) signaling and identified the Hippo pathway as a new potentially oncogenic feature of Pheo.

Objective: Women living with HIV (WLWH) experience psychosocial stress related to social-structural vulnerabilities. To investigate neuroendocrine pathways linking stress and increased cardiovascular disease risk among WLWH, we evaluated associations between psychosocial stress (i.e., perceived stress, posttraumatic stress, and experiences of race- and gender-based harassment) and a composite neuroendocrine biomarker index among WLWH and women without HIV., Methods: In 2019-2020, Women's Interagency HIV Study participants in Washington, DC completed a questionnaire and provided blood and 12-hour overnight urine samples for testing of serum dehydroepiandrosterone sulfate (DHEA-S) and urinary free cortisol, epinephrine, and norepinephrine. Psychosocial stress was measured using the Perceived Stress Scale, PTSD Checklist-Civilian Version, and Racialized Sexual Harassment Scale. Latent profile analysis was used to classify participants into low (38%), moderate (44%), and high (18%) stress groups. Composite biomarker index scores between 0-4 were assigned based on participants' number of neuroendocrine biomarkers in high-risk quartiles (≥75th percentile for cortisol, epinephrine, and norepinephrine and ≤25th percentile for DHEA-S). We evaluated associations between latent profile and composite biomarker index values using multivariable linear regression, adjusting for socio-demographic, behavioral, metabolic, and HIV-related factors., Results: Among 90 women, 62% were WLWH, 53% were non-Hispanic Black, and median age was 55 years. In full multivariable models, there was no statistically significant association between psychosocial stress and composite biomarker index values among all women independent of HIV status. High (vs. low) psychosocial stress was positively associated with higher mean composite biomarker index values among all monoracial Black women (adjusted β = 1.32; 95% CI: 0.20-2.43), Black WLWH (adjusted β = 1.93; 95% CI: 0.02-3.83) and Black HIV-negative women (adjusted β = 2.54; 95% CI: 0.41-4.67)., Conclusions: Despite a null association in the overall sample, greater psychosocial stress was positively associated with higher neuroendocrine biomarker concentrations among Black women, highlighting a plausible mechanism by which psychosocial stress could contribute to cardiovascular disease risk., Competing Interests: One of the authors [ML] is currently affiliated with a commercial entity, Westat. Data collection and analysis for this study occurred prior to his current affiliation with Westat, while he was affiliated with The George Washington University. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

[Figure: see text].

A hydrogel based on titanium dioxide/MXene with polyvinyl alcohol/graphene oxide (TiO 2 /MXene-PVA/GO) composite was successfully formulated and applied to modify a screen-printed carbon electrode (SPCE) for urinary norepinephrine (NE) detection. The characterization confirmed that a nanocomposite hydrogel structure of TiO 2 /MXene-PVA/GO was formed. The as-prepared hydrogel substantially enhanced the sensor performances due to electrocatalytic activity of TiO 2 , high conductivity of MXene, and auto-sample preconcentration via PVA/GO hydrogel. The electrochemical behavior of NE was investigated by cyclic voltammetry and amperometry. Under optimized conditions, the TiO 2 /MXene-PVA/GO hydrogel/SPCE response due to the oxidation of NE at +0.4 V (vs. Ag|AgCl) is proportional to the concentration of NE over 0.01 to 1.00 μM (R 2  = 0.9968) and 1.00 to 60.0 μM (R 2  = 0.9936) ranges with a detection limit (3σ) of 6 nM without interferent effect from common interferences in urine. Furthermore, this sensor was employed for urinary NE determination and validated by high performance liquid chromatography (HPLC) with a UV detector at 280 nm; the average recovery was found to be 97.6 to 102%, with a relative standard deviation (RSD) less than 4.9%. This device was sensitive enough to evaluate an early stage of neurological disorder via detecting clinically relevant NE level. Eventually, it was integrated with pantyliners which could be a potential wearable sensor in the near future., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

For correct and reliable experimental in vivo assessment of antistress effect of various bioactive substances, appropriate biomodels reproducing stress and organism response to stress in laboratory animals should be chosen. We chose treadmill test for simulating exhaustive physical load and forced immobilization accompanied by disorders of physiological and psychological condition. Verification of the models used indicates their wide applicability for testing certain biological manifestations under reproduced stress exposure., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Genetic approach using rat congenic lines between SHRSP/Izm and WKY/Izm identified stromal interaction molecule 1 ( Stim1 ), an essential component of store-operated Ca 2+ entry (SOCE), as a promising candidate gene responsible for the exaggerated sympathetic response to stress in SHRSP. Since SHRSP has a nonsense mutation in Stim1 resulting in the expression of a truncated form of STIM1 that caused reduction of SOCE activity in primary cultured cerebral astrocytes, we created SHRSP/Izm knocked-in with the wild-type Stim1 (KI SHRSP) by the CRISPR/Cas9 method to investigate whether the functional recovery of STIM1 would mitigate sympatho-excitation to stress in vivo in SHRSP. No potential off-target nucleotide substitutions/deletions/insertions were found in KI SHRSP. Western blotting and fluorescent Ca 2+ imaging of astrocytes confirmed wild-type STIM1 expression and restored SOCE activity in astrocytes from KI SHRSP, respectively. Blood pressure (BP) measured by the tail-cuff method at 12, 16, and 20 weeks of age did not significantly differ between SHRSP and KI SHRSP, while the heart rate of KI SHRSP at 16 and 20 weeks of age was significantly lower than that of age-matched SHRSP. Unexpectedly, the sympathetic response to stress (evaluated with urinary excretion of norepinephrine under cold stress and BP elevation under cold/restraint stress) did not significantly differ between SHRSP and KI SHRSP. The present results indicated that the functional deficit of STIM1 was not a genetic determinant of the exaggerated sympathetic response to stress in SHRSP and that it would be necessary to explore other candidates within the congenic fragment on chromosome 1.

Background: Experiences of discrimination are a risk factor for subsequent cardiovascular disease. However, there is a lack of longitudinal research examining associations between discrimination and urinary catecholamines. This is surprising given the likely mediating role of sympathetic nervous system dysregulation in the association between psychosocial stress and cardiovascular morbidity., Purpose: The current study examined the 3 year longitudinal association between experiences of discrimination and urinary catecholamines., Methods: The sample included 149 college students (mean age at baseline = 18.8, standard deviation = 0.96; 45% Black/African American; 55% White/European American). Concentrations of epinephrine and norepinephrine-urinary catecholamines with established links to psychosocial stress exposure and subsequent morbidity-were determined from 12 hr overnight samples., Results: Results indicated that experiences of discrimination were associated with increases in both epinephrine (β = .284, standard error [SE] = .117, p = .015) and norepinephrine (β = .306, SE = .114, p = .001). These longitudinal associations persisted after adjusting for negative affect, depression, and rejection sensitivity and did not vary as a function of race/ethnicity., Conclusions: Results suggest that examination of overnight urinary catecholamines as a biological mediator of associations between experiences of discrimination and cardiovascular morbidity is warranted., (© Society of Behavioral Medicine 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Multiple stressors, including 24-h-shifts characterise the working environment of physicians, influencing well-being, health and performance. We aimed to evaluate the effect of the stressor 24-h-shift on the adrenal medullary and sympathoneural system in physicians with the hypothesis that shift work might have different impacts on both systems. Twenty-two physicians collected two 12-h-urine samples ("daytime" and "nighttime") during a 24-h shift ("on-duty") and on a free weekend ("off-duty"), respectively. Urinary excretion rates per m 2 body surface area were assessed for the catecholamines epinephrine, norepinephrine and their respective free O-methylated metabolites metanephrine and normetanephrine by LC-MS/MS-analysis. The stressor provoked differential responses of epinephrine and norepinephrine. Epinephrine excretion rates showed significant increases from off to on duty. The largest proportional change (off-duty to on-duty) for epinephrine was observed for nighttime (205%), the increase for daytime was 84%. An increase in norepinephrine from off to on duty was only visible for nighttime collections. For the catecholamine metabolites, normetanephrine paralleled norepinephrine and exhibited an increase in excretion from off to on duty during nighttime collections of 53% whereas there was no change during daytime collections (3%). In conclusion: Whilst the 24-h-shift-work stressor in physicians activates the sympatho-adrenomedullary system, represented by epinephrine, the sympathoneural response through norepinephrine reflects mainly an ambulatory position during working hours., (Copyright © 2020 Boettcher, Sommer, Peitzsch, Zimmer, Eisenhofer and Wudy.)

Background: Interindividual variability in 24-hour energy expenditure (24EE) during energy-balance conditions is mainly determined by differences in body composition and demographic factors. Previous studies suggested that 24EE might also be influenced by sympathetic nervous system activity via catecholamine (norepinephrine, epinephrine) secretion. Therefore, we analyzed the association between catecholamines and energy expenditure in 202 individuals from a heterogeneous population of mixed ethnicities., Methods: Participants (n = 202, 33% female, 14% black, 32% white, 41% Native American, 11% Hispanic, age: 36.9 ± 10.3 y [mean ± SD], percentage body fat: 30.3 ± 9.4) resided in a whole-room calorimeter over 24 hours during carefully controlled energy-balance conditions to measure 24EE and its components: sleeping metabolic rate (SMR), awake-fed thermogenesis (AFT), and spontaneous physical activity (SPA). Urine samples were collected, and 24-h urinary epinephrine and norepinephrine excretion rates were assessed by high-performance liquid chromatography., Results: Both catecholamines were associated with 24EE and SMR (norepinephrine: +27 and +19 kcal/d per 10 μg/24h; epinephrine: +18 and +10 kcal/d per 1 μg/24h) in separate analyses after adjustment for age, sex, ethnicity, fat mass, fat-free mass, calorimeter room, temperature, and physical activity. In a multivariate model including both norepinephrine and epinephrine, only norepinephrine was independently associated with both 24EE and SMR (both P < .008), whereas epinephrine became insignificant. Neither epinephrine nor norepinephrine were associated with adjusted AFT (both P = .37) but epinephrine was associated with adjusted SPA (+0.5% per 1 μg/24h)., Conclusions: Our data provide compelling evidence that sympathetic nervous system activity, mediated via norepinephrine, is a determinant of human energy expenditure during nonstressed, eucaloric conditions., (Published by Oxford University Press on behalf of the Endocrine Society 2020.)

Competing Interests: Declaration of competing interest We declare that the manuscript is original, has not been published before and is not currently being considered for publication elsewhere; moreover, it does not contain material whose publication requires the permission from third parties. So, we specify that there are no duplicate publication problems, financial or other relationships that could give rise to conflicts of interest. We confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. We further confirm that the order of authors listed in the manuscript has been approved by all of us. The authors submitting the present study have also obtained required approval for submission from authorized principal in their own organization. Finally, as we believe that color art is necessary to the presentation of our work, we declare to be prepared to pay the substantial costs associated with color art reproduction.

Catecholamine neurotransmitters, specifically, dopamine (DA), epinephrine (EP), and norepinephrine (NE), are known as substantial indicators of various neurological diseases. Developing rapid detection methods capable of simultaneously screening their concentrations is highly desired for early clinical diagnosis of such diseases. To this aim, we have designed an optical sensor array using three fluorescent dyes with distinct emission bands and have monitored variations in their emission profiles upon the addition of DA, EP, and NE in the presence of gold ions. Because of the different reducing power of catecholamines, differently sized gold nanoparticles (GNPs) with different levels of aggregation were generated, resulting in different amounts of spectral overlap between the absorption band of the in situ generated plasmonic GNPs and the emission bands of the fluorescent dyes. These energy-transfer-based fingerprint profiles were used to discriminate the neurotransmitters by applying pattern recognition methods including linear discriminant analysis (LDA) and artificial neural networks (ANN) and to determine their concentration using multiple linear regression (MLR). Our proposed array also showed a good performance in the discrimination of DA, EP, and NE in complex biological media such as human urine.

Objectives: The aim of this study was to investigate the effect of repeated binge drinking and moderate alcohol consumption in young adults on arterial stiffness and sympathetic activity., Methods: We enrolled 49 healthy young adults, free of cardiovascular diseases (25 men; age: 23.5 ± 0.4 years; BMI: 23.4 ± 0.4 kg/m; mean ± S.E). Individuals included were those with a history of repeated binge drinking (>2 years duration; n = 20), drank at moderate levels (MODs, >5 years duration; n = 16) and abstained from alcohol (last 2-3 years; n = 13). Arterial stiffness was assessed using carotid to femoral pulse wave velocity (cfPWV) and sympathetic activity was assessed using 24-h urinary norepinephrine levels. Also measured was aortic SBP and augmentation index (AIx), a measure of wave reflection., Results: Binge drinkers and MODs had higher cfPWV than alcohol abstainers (0.6 and 0.5 m/s, respectively; P ≤ 0.04). In addition, binge drinkers had higher urinary norepinephrine levels than MODs and alcohol abstainers (P < 0.05). Higher cfPWV were correlated with higher norepinephrine levels (r = 0.35. P = 0.02). Aortic SBP (P = 0.2) and AIx (P = 0.96) were similar among binge drinkers, MODs and alcohol abstainers., Conclusion: Our findings suggest that repeated exposure to alcohol, regardless of drinking pattern, may increase aortic arterial stiffness in healthy young adults. In addition, sympathetic activation, reflected by increased 24-h urinary norepinephrine levels, may contribute to alcohol-induced arterial stiffening in young adults.

Many patients with obstructive sleep apnea (OSA), but not all, have a reduction in blood pressure (BP) with positive airway pressure (PAP) treatment. Our objective was to determine whether the BP response following PAP treatment is related to obesity. A total of 188 adults with OSA underwent 24-hour BP monitoring and 24-hour urinary norepinephrine collection at baseline. Obesity was assessed by waist circumference, body mass index, and abdominal visceral fat volume. Participants adherent to PAP treatment were reassessed after 4 months. Primary outcomes were 24-hour mean arterial pressure (MAP) and 24-hour urinary norepinephrine level. Obstructive sleep apnea participants had a significant reduction in 24-hour MAP following PAP treatment (-1.22 [95% CI: -2.38, -0.06] mm Hg; P = .039). No significant correlations were present with any of the 3 obesity measures for BP or urinary norepinephrine measures at baseline in all OSA participants or for changes in BP measures in participants adherent to PAP treatment. Changes in BP measures following treatment were not correlated with baseline or change in urinary norepinephrine. Similar results were obtained when BP or urinary norepinephrine measures were compared between participants dichotomized using the sex-specific median of each obesity measure. Greater reductions in urinary norepinephrine were correlated with higher waist circumference (rho = -0.21, P = .037), with a greater decrease from baseline in obese compared to non-obese participants (-6.26 [-8.82, -3.69] vs -2.14 [-4.63, 0.35] ng/mg creatinine; P = .027). The results indicate that the BP response to PAP treatment in adults with OSA is not related to obesity or urinary norepinephrine levels., (©2019 Wiley Periodicals, Inc.)

Objectives: Increased sympathetic activity is proposed to be a mechanism of high blood pressure in children born small for gestational age. Ambulatory blood pressure monitoring is a form of blood pressure measurement that can detect high blood pressure outside the hospital in patients with normal office blood pressure. This condition is called masked hypertension. There are limited data on association between ambulatory blood pressure and urinary catecholamines during exposure to stress in children born small for gestational age., Methods: Nineteen children born small for gestational age and 17 healthy controls ages 6-14 years old were included. Demographic data and office blood pressure were collected. Urinary catecholamines were collected before and after exposure to stress including mathematical test and venipuncture. Afterwards, ambulatory blood pressure monitoring was performed to obtain 24-hour blood pressure profiles., Results: All children had normal office blood pressure but ambulatory blood pressure monitoring revealed masked hypertension in six children born small for gestational age (32%) and two controls (11.7%). After stress, median percentage of increase in urine norepinephrine levels was greater in children born small for gestational age with masked hypertension than that of children born small for gestational age without masked hypertension (9.2 vs. -13.2 μg/g creatinine, P = 0.05). There was no increase in urine norepinephrine levels in controls with masked hypertension. Among children born small for gestational age, awake SBP z-scores had significant positive correlations with pre- and post-stress urinary dopamine levels (r = 0.530, P = 0.02 and r = 0.597, P = 0.007, respectively)., Conclusion: Masked hypertension is not uncommon in children born small for gestational age. After stress, urinary norepinephrine levels were increased in children born small for gestational age with masked hypertension.

Background: Whether the reduction of heart rate with ivabradine (IVA) could affect sympathetic activation and cardiac innervation in heart failure (HF) remains unknown., Purpose: The present study assessed the chronic effects of IVA and β-blocker on the systemic and local sympathetic nervous systems of hypertensive animals with HF., Methods and Results: The Dahl salt-sensitive rats received chronic IVA, bisoprolol (BIS), or placebo (CTL) therapy. The survival of the animal models with IVA and BIS significantly improved (median; 19.7 in IVA and 19.7 in BIS vs 17.0 weeks in CTL, P < .001). A similar decrease in 24-hour heart rate (mean; 305 in IVA and 329 in BIS vs 388 beats/min in CTL, P < .001) without effect on blood pressure, and an improvement in the left ventricular dysfunction (mean fractional shortening; 56.7% in IVA and 47.8% in BIS vs 39.0% in CTL, P < .001) were observed in the animals with IVA and BIS. However, a negative inotropic effect was only observed in the animals with BIS. Excessive urinary noradrenaline excretion in animals with CTL was only suppressed with the use of IVA (mean; 1.35 μg/d in IVA and 1.95 μg/d in BIS vs 2.27 μg/d in CTL, P = .002). In contrast, atrial noradrenaline and acetylcholine depletion in the animals with CTL improved and the tyrosine hydroxylase expression in the both atria were restored with the use of both IVA and BIS., Conclusions: IVA therapy improved the survival of hypertensive animals with HF. Furthermore, it was associated with the amelioration of systemic sympathetic activation and cardiac sympathetic and parasympathetic nerve innervations. Chronic β-blocker therapy with negative inotropic effects had beneficial effects only on cardiac innervations.

In this work, a facile and label-free ratiometric sensor is constructed for selective determination of norepinephrine (NE) by coupling second-order scattering (SOS) and fluorescence, two different and independent optical signals. Herein, polyethyleneimine (PEI) dilute solution medium shows an intensive SOS signal without any fluorescence response. Interestingly, NE can be selectively induced by PEI to emit bright fluorescence, and meanwhile causes an observable decrease in the SOS signal due to the interactions between NE and PEI. The simultaneous variation of the two independent signals can be used for ratiometric sensing of NE. Under the optimal conditions, the resultant ratiometric sensor displays high sensitivity and selectivity toward NE by simultaneously monitoring fluorescence and SOS signals with the same excitation wavelength. The proposed sensor exhibits a good linear relationship versus NE concentration in the range of 10.0 nM-45.0 μM with a detection limit of 2.0 nM (S/N = 3) and has been successfully applied to the determination of NE in real samples without the use of any extra reagent. The combination of fluorescence and SOS signals provides a new scheme for ratiometric sensor design, greatly simplifying experimental procedure and effectively enhancing detection accuracy. Moreover, the proposed analytical strategy further broadens the application of dilute solutions of polymers in research into optical sensor and green analytical chemistry. Graphical abstract.

Background: Autonomic nervous system effects have been hypothesized as a mechanism of air pollutant health effects, though scant prior epidemiologic research has examined the association between air pollutants and catecholamines., Objectives: To examine the association of long-term air pollutants with three urinary catecholamines: dopamine (DA), epinephrine (EPI), and norepinephrine (NE). As a secondary aim, we also examined the association between short-term (or acute) exposure to fine particulate matter [particulate matter with aerodynamic diameter [Formula: see text] ([Formula: see text])] and those catecholamines., Methods: We used data from the Multi-Ethnic Study of Atherosclerosis (MESA) and two of its ancillary studies, the MESA Air Pollution Study and the MESA Stress Study, to provide exposure and outcome data. DA, EPI, and NE from urine samples were collected from 2004 to 2006 from 1,002 participants in the New York, New York, and Los Angeles, California, study sites. Spatiotemporal models incorporated cohort-specific monitoring and estimated annual average pollutant concentrations ([Formula: see text], [Formula: see text], [Formula: see text] and black carbon) at participants' homes the year prior to urine collection. Secondarily, short-term [Formula: see text] was evaluated (day of, day prior, and 2- to 5-d lags prior to urine collection). Several covariates were considered confounders (age, race, sex, site, socioeconomic status, cardiovascular disease risk factors, psychosocial stressors, and medication use) in linear regression models., Results: A [Formula: see text] higher annual [Formula: see text] concentration was associated with 6.3% higher mean EPI level [95% confidence interval (CI): 0.3%, 12.6%]. A 2-[Formula: see text] higher annual ambient [Formula: see text] concentration was associated with 9.1% higher mean EPI (95% CI: 3.2%, 15.3%) and 4.4% higher DA level (95% CI: 1%, 7.9%). [Formula: see text], black carbon, and short-term [Formula: see text] exposures were not significantly associated with any of the catecholamines., Conclusions: We found an association between EPI and long-term concentrations of [Formula: see text] and [Formula: see text] and an association between DA and long-term ambient [Formula: see text]. These novel findings provide modest support for the hypothesis that air pollutant exposures are related to sympathetic nervous system activation. https://doi.org/10.1289/EHP3286.

Glucose intolerance is often observed in patients with pheochromocytoma. However, it remains controversial issue that glucose intolerance on pheochromocytoma is caused by impaired insulin secretion and/or by increased insulin resistance. We aimed to reveal the mechanism of glucose intolerance on pheochromocytoma with regard to the type and amount of catecholamines released. We evaluated 12 individuals diagnosed with pheochromocytoma and who underwent surgery to remove it. We examined glycemic parameters before and after surgery and investigated the association between the change of parameters of insulin secretion (homeostasis model assessment of β-cell function (HOMA-β)), insulin resistance (homeostasis model assessment of insulin resistance (HOMA-IR)) and that of urinary levels of metanephrine/normetanephrine before and after surgery. Overall, fasting plasma glucose, glycated hemoglobin (HbA1c), HOMA-β, and HOMA-IR were improved significantly after surgery. Regression analysis showed that the improvement in HOMA-β from before to after surgery was significantly positively associated with an improvement in urinary levels of metanephrine from before to after surgery and showed a significantly negative association with improvement in urinary levels of normetanephrine from before to after surgery. The improvement in HOMA-IR from before to after surgery was significantly positively associated with an improvement in urinary levels of normetanephrine from before to after surgery. Our results showed that pheochromocytoma extirpation improved glycemic parameters. Furthermore, the different effects elicited by excess amounts of adrenaline and noradrenaline on glucose intolerance were demonstrated.

Background: The pressor effect of L-threo-3,4-dihydroxyphenylserine (L-DOPS, droxidopa, Northera™) results from conversion of L-DOPS to norepinephrine (NE) in cells expressing L-aromatic-amino-acid decarboxylase (LAAAD). After L-DOPS administration the increase in systemic plasma NE is too small to explain the increase in blood pressure. Renal proximal tubular cells abundantly express LAAAD. Since NE generated locally in the kidneys could contribute to the pressor effect of L-DOPS, in this study we assessed renal conversion of L-DOPS to NE., Methods: Ten patients who were taking L-DOPS for symptomatic orthostatic hypotension had blood and urine sampled about 2 h after the last L-DOPS dose. L-DOPS and NE were assayed by alumina extraction followed by liquid chromatography with electrochemical detection. Data were compared in patients off vs. on levodopa/carbidopa., Results: In patients off levodopa/carbidopa the ratio of NE/L-DOPS in urine averaged 63 times that in plasma (p = 0.0009 by t test applied to log-transformed data). In marked contrast, in the three patients on levodopa/carbidopa the ratio of NE/L-DOPS in urine did not differ from that in plasma., Conclusion: There is extensive renal production of NE from L-DOPS. Carbidopa seems to attenuate the conversion of L-DOPS to NE in the kidneys. Further research is needed to assess whether the proposed paracrine effect of L-DOPS in the kidneys contributes to the systemic pressor response.

Objectives: To determine the incidence and preoperative risk factors of post-excisional hypoglycemia in patients undergoing pheochromocytoma resection., Methods: Patients who underwent surgical resection of pheochromocytoma at a single institution were retrospectively enrolled in the present study. The primary end-point was the development of post-excisional hypoglycemia; that is, a serum glucose level <70 mg/dL. The serum levels of immunoreactive insulin and glucose levels during the preoperative oral glucose-tolerance test and surgery were analyzed to elucidate the mechanism of hypoglycemia., Results: A total of 49 patients underwent surgical resection of pheochromocytoma, of which 21 patients (43%) developed post-excisional hypoglycemia. The incidence of hypoglycemia was not statistically different between patients with adrenal tumors and those with extra-adrenal tumors (18/41 [44%] vs 3/8 [38%], respectively, P = 0.73). There was no difference in the immunoreactive insulin/glucose ratio during the preoperative oral glucose-tolerance test between patients with and those without post-excisional hypoglycemia. The intraoperative immunoreactive insulin/glucose ratio was significantly higher in patients with hypoglycemia than in those without hypoglycemia. A higher 24-h urinary epinephrine level, but not norepinephrine level, was a predictive factor for post-excisional hypoglycemia., Conclusions: Post-excisional hypoglycemia is a frequent complication of pheochromocytoma resection, irrespective of the tumor location, and might be common in patients with epinephrine-predominant tumors. All patients undergoing resection of adrenal and extra-adrenal pheochromocytoma require intensive monitoring of serum glucose levels during and after surgery., (© 2018 The Japanese Urological Association.)

Introduction: Hypertension, particularly in black populations, is often accompanied by augmented sympathetic nervous system activity and suppressed renin activity, indicative of possible blood pressure (BP) dysregulation. The potential role of the interrelationship between the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system in the context of low-renin conditions is unclear. We therefore explored whether surrogate measures of sympathetic activity [noradrenaline, 24-hour heart rate (HR) and percentage (%) dipping of night-time HR] relate to renin, aldosterone and aldosterone-to-renin ratio (ARR) in black and white South Africans., Methods: We included black (n = 127) and white (n = 179) males and females aged 20-63 years. We measured 24-hour BP and HR, and calculated night-time dipping. We determined renin and aldosterone levels in plasma and calculated ARR. Noradrenaline and creatinine levels were determined in urine and the noradrenaline:creatinine ratio was calculated., Results: More blacks had low renin levels (80.3%) compared to whites (58.7%) (p < 0.001). In univariate and after multivariate analyses the following significant associations were evident in only the black group: HR dipping was associated negatively with aldosterone level (β = -0.18, p = 0.024) and ARR (β = -0.20, p = 0.011), while 24-hour HR was associated positively with renin level (β = 0.20, p = 0.024). Additionally, there was a borderline significant positive association between noradrenaline:creatinine ratio and aldosterone level (β = 0.19, p = 0.051)., Conclusions: The observed associations between surrogate measures of sympathetic nervous system activity and components of the RAAS in the black group suggest that the adverse effects of aldosterone and its ratio to renin on the cardiovascular system may be coupled to the effects of the sympathetic nervous system.

Herbal medicines, acupuncture and moxibustion are often used for unidentified complaints. It is well known that catecholamine secreted by the sympatho-adrenal medullary system primarily functions to increase cardiac output and raise glucose levels in the blood during acute stress. In the present study, the effects of yokukansankachimpihange (YKSKCH, a Kampo medicine) on urinary catecholamine in mice that were repeatedly stressed by restraining were examined. Restraint stress (240 min/d×3 d×3 cycles, daytime: 12:00-16:00) induced a marked increase in noradrenaline (NA) and adrenaline (A) levels in the urine. Oral administration of YKSKCH (750 mg/kg of body weight) significantly inhibited the increase in urinary NA and A levels in mice after repeated restraint stress. In addition, the NA/dopamine (physical stress) and A/dopamine (mental stress) ratios were lower in the 750 mg/kg YKSKCH-treated group than in the control group. The tail suspension test was also performed and locomotor activity was investigated. Oral administration of YKSKCH at 750 mg/kg significantly reduced the immobility time, which was longer in mice after repeated restraint stress. Furthermore, oral administration of YKSKCH at 750 mg/kg increased locomotor activity, which was lower in mice after repeated restraint stress. These results suggest that YKSKCH has positive effects on mental and physical stress after repeated restraint stress, without reducing locomotor activity.

Owing to its dual role as a hormone and neurotransmitter, norepinephrine (NE) detection is of great significance to biomedical diagnosis. In the present work, we have explored intense green fluorescence of poly (norepinephrine) (PNE) nanoparticles synthesized by oxidizing NE in alkaline condition, in combination with red fluorescent bovine serum albumin-stabilized gold nanoclusters (BSA-AuNCs) for naked-eye detection of NE. The effect of sodium hydroxide on the emission behavior of NE was studied. The surface morphology and optical properties of PNE nanoparticles were characterized by UV-Vis, fluorescence, FTIR, Transmission Electron Microscopy (TEM) and Dynamic Light Scattering (DLS) techniques. For ratiometric sensing of NE, red fluorescent BSA-AuNCs were served as an internal reference while NE delivered a new emission peak at 527 nm, resulting in a wide distinguishable color change from strong red into red, pink, orange, and green under a UV lamp. The ratiometric approach was demonstrated to be highly sensitive and selective for NE detection against even structurally similar biomolecules with a detection limit of 49 nmol L -1 . Furthermore, the proposed method was successfully applied to determine NE in urine samples., (Copyright © 2018 Elsevier B.V. All rights reserved.)

In sleep apnea syndrome (SAS), chronic intermittent hypoxia (CIH) is believed to activate the sympathetic nerve system, and is thus involved in cardiovascular diseases (CVD). However, since patients with SAS are often already obese, and have diabetes and/or hypertension (HT), the effects of CIH alone on sympathetic nerve activation and its impacts on CVD are largely unknown. We, therefore, examined the effects of CIH on sympathetic nerve activation in non-obese mice to determine whether renal sympathetic nerve denervation (RD) could ameliorate CIH-mediated cardiovascular effects. Male C57BL/6 (WT) mice were exposed to normal (FiO 2 21%) or CIH (10% O 2 , 12 times/h, 8 h/day) conditions for 4 weeks with or without RD treatment. Increased urinary norepinephrine (NE), 8-OHdG, and angiotensinogen levels and elevated serum asymmetric dimethyl arginine levels were observed in the CIH model. Concomitant with these changes, blood pressure levels were significantly elevated by CIH treatment. However, these deleterious effects by CIH were completely blocked by RD treatment. The present study demonstrated that CIH-mediated renal sympathetic nerve activation is involved in increased systemic oxidative stress, endothelial dysfunction, and renin-angiotensin system activation, thereby contributing to the development of HT and CVD, thus could be an important therapeutic target in patients with SAS.

Carbon nanomaterials possess superb properties and have contributed considerably to the advancement of integrated point-of-care chemical and biological sensing devices. Graphene has been widely researched as a signal transducing and sensing material. Here, a grass-like laser-scribed graphene (LSG) was synthesized by direct laser induction on common polyimide plastics. The resulting LSG grass was employed as a disposable electrochemical sensor for the detection of three neurotransmitters, dopamine (DA), epinephrine (EP), and norepinephrine (NE), and in the presence of uric acid and ascorbic acid as potential interferants, using differential pulse voltammetry and cyclic voltammetry. The LSG grass sensor achieved sensitivities of 0.243, 0.067, and 0.110 μA μM -1 for DA, EP, and NE, respectively, whereas the limits of detection were 0.43, 1.1, and 1.3 μM, respectively. The selectivity of LSG grass was excellent for competing biomarkers with high structural similarity (EP vs NE and EP vs DA). The exceptional performance of LSG grass for DA, EP, and NE detection holds a promising future for carbon nanomaterial sensors with unique surface morphologies.

Fixating on the present moment rather than considering future consequences of behavior is considered to be a hallmark of drug addiction. As an example, cigarette smokers devalue delayed consequences to a greater extent than nonsmokers, and former smokers devalue delayed consequences more than nonsmokers, but less than current smokers. Further, cigarette smokers have higher norepinephrine levels than nonsmokers, which is indicative of poor future health outcomes. It is unclear how duration of cigarette smoking may impact these associations. The current secondary analysis of publicly available data investigated whether extent of future thinking is associated with smoking duration, as well as norepinephrine level, in a large national US sample (N = 985) of current, former, and never smokers. Individuals scoring lower on future thinking tended to smoke for longer durations and had higher norepinephrine levels relative to individuals scoring higher on future thinking. In addition, duration of cigarette abstinence interacted significantly with future thinking and smoking duration for former smokers. Specifically, the mediation relationship between future thinking, smoking duration, and norepinephrine level for former smokers was strongest at shorter durations of cigarette abstinence and decreased as a function of increasing duration of cigarette abstinence. Overall, results from this study suggest the potential importance of implementing smoking cessation treatments as early as possible for smokers and support future thinking as a potential therapeutic target for smoking cessation treatment., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Norepinephrine is secreted under conditions of stress in humans. The ability of bacteria to sense mammalian hormone may have a role in propagation of infection. The present study investigated the effect of norepinephrine on in vitro growth of uropathogenic E. coli (UPEC) and the effect of silodosin on norepinephrine-induced changes. The spot urine samples were collected from 56 individuals (14 diabetic patients with UTI, 14 diabetic without UTI, 14 non-diabetic UTI and 14 healthy volunteer controls) for the measurement of urinary norepinephrine concentrations. The concentration of norepinephrine, as found in urine of human subjects, was reproduced in artificial urine medium to study the growth of UPEC. The norepinephrine concentration showing maximum growth response was selected to study the effect of silodosin on the growth inhibition of UPEC. Result showed significantly elevated urinary norepinephrine in diabetic patients with and without UTI and also in nondiabetic UTI groups. The norepinephrine concentration equivalent to that in diabetic UTI patients enhanced the growth of UPEC. Furthermore, silodosin (0.32 μM) inhibited the growth of the UPEC., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Classically, pheochromocytomas and paragangliomas result in hypertension secondary to an excess release of catecholamines. However, when the tumor arises near the renal hilum, hypertension may also be secondary to renal artery stenosis, which can occur via several purported mechanisms. We describe an unusual case of a hereditary, extra-adrenal pheochromocytoma causing right lower pole renal artery pseudostenosis, pertinent radiologic signs, relevant surgical findings, and subsequent resolution after extirpative surgery., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aims: To inform research on the etiology and prevention of substance use among rural African American youth by (a) identifying developmental trajectory classes of cannabis use and heavy drinking across adolescence and young adulthood and (b) examining associations between trajectory class membership and multi-level assessments of risk factors., Design: A prospective study spanning 9 years with assessments of cannabis use and heavy drinking, the catecholamines epinephrine and norepinephrine, perceived stress and psychosocial risk factors., Setting: Rural communities in the southeastern United States., Participants: African American youth (n = 518)., Measurements: Participants were assessed for cannabis use and heavy drinking at seven assessments beginning at 16 years of age and continuing to 25 years of age. At age 19, participants provided overnight urine voids that were assayed for catecholamines, a biological marker of life stress resulting from sympathetic nervous system activation. At ages 16 and 19, participants provided information on malleable psychosocial risk factors., Findings: Latent class growth models revealed three distinct trajectory classes for cannabis use and for heavy drinking. Higher levels of circulating stress hormones and perceived stress were associated with classes reporting greater substance use over time (all Ps < 0.05). A composite of selected risk factors discriminated class membership (all Ps < 0.05). Trajectory classes characterized by rapid usage increases in early adulthood exhibited the greatest increase in deviant peer affiliations between ages 16 and 19 years., Conclusions: Rural African American youth's cannabis use and heavy drinking across adolescence and young adulthood demonstrate distinct developmental courses; a small number of risk factors and measures of biological and perceived stress differentiate class membership prognostically. Variability over time in these measures, specifically an increase in deviant peer affiliation, may help to account for steep increases in young adulthood., (© 2018 Society for the Study of Addiction.)

Context: Night games are a regular occurrence for team-sport athletes, yet sleep complaints following night competitions are common. The mechanisms responsible for reported sleep difficulty in athletes are not understood., Methods: An observational crossover design investigating a night netball game and a time-matched rest day in 12 netball athletes was conducted to ascertain differences in physiological (core temperature), psychometric (state and trait), and neuroendocrine (adrenaline, noradrenaline, and cortisol) responses., Results: Following the night game, athletes experienced reduced sleep durations, lower sleep efficiency, early awakenings, and poorer subjective sleep ratings compared with the rest day. No differences were found between core temperature, state psychometric measures, and cortisol at bedtime. Adrenaline and noradrenaline concentrations were elevated compared with the time-matched rest day prior to (26.92 [15.88] vs 12.90 [5.71] and 232.6 [148.1] vs 97.83 [36.43] nmol/L, respectively) and following the night game (18.67 [13.26] vs 11.92 [4.56] and 234.1 [137.2] vs 88.58 [54.08] nmol/L, respectively); however, the concentrations did not correlate to the sleep variables (duration, efficiency, and sleep-onset latency). A correlation (r s  = -.611) between sleep efficiency and hyperarousal (trait psychometric measure) was found., Conclusions: Athletes experienced poor sleep following a night game. Furthermore, results suggest that athletes who have a tendency toward a high trait arousal may be more susceptible to sleep complaints following a night game. These data expand knowledge and refute frequently hypothesized explanations for poor sleep following night competition. The results may also help support staff and coaches target strategies for individual athletes at a higher risk of sleep complaints.

Rationale: Paraganglioma is rare in children and most pheochromocytomas originate in the adrenal gland., Patient Concerns: The clinical characteristics, diagnosis, and managements in a 9-year-old boy who presented with vomiting and occasional headache with a blood pressure of 210/170 mm Hg was retrospectively reviewed. CT scan of the chest revealed a 7 × 5-cm-sized soft tissue mass in the left paraspinal area. Biochemical reports revealed elevated levels of serum norepinephrine, urine norepinephrine, urine dopamine, and serum neuron specific enolase., Diagnoses: The immunohistochemical studies suggested that the tumor was a paraganglioma of the posterior mediastinum., Interventions: The patient underwent mass resection with thoracotomy. Before operation, the patient was prepared by orally administering captopril, propranolol hydrochloride, and phenoxybenzamine. Body fluid volume was also prepared by vein and mouth in 3 days., Outcomes: The patient was followed up postoperatively for 1 year without recurrence., Lessons: We should be highly vigilant the pediatric tumor of the posterior mediastinum with vomiting and headache as the first clinical manifestation.

Context: In healthy adults with detectable cold-induced brown adipose tissue activation (CIBA), the relationships between sympathetic nervous system (SNS) or thyroid activity during energy balance (EBL) with CIBA and body composition change are undetermined., Objective: To investigate the relationships between CIBA and thermoneutral catecholamines and thyroid hormones measured during EBL and to determine if CIBA, catecholamines, or thyroid hormones predict body composition changes., Design, Setting, Participants, and Interventions: Twelve healthy volunteers (seven male and five female) with positive CIBA [>2 standardized uptake value (g/mL)] had 24-hour energy expenditure (24hEE) assessed during EBL via whole-room indirect calorimetry while residing on a clinical research unit. Positron emission tomography/computed tomography scans were performed after exposure to 16°C for 2 hours to quantify CIBA., Main Outcome Measures: CIBA, 24hEE during EBL, and thermoneutrality with concomitant measurement of urinary catecholamines and plasma free T3 and free T4. Body composition at baseline and 6 months by dual-energy X-ray absorptiometry., Results: Lower urinary norepinephrine and free T4 were associated with higher CIBA (r = -0.65, P = 0.03; and r = -0.75, P < 0.01, respectively), but CIBA was not associated with 24hEE at thermoneutrality (P = 0.77). Lower CIBA (β = -3.5 kg/standardized uptake value; P < 0.01) predicted fat mass gain, whereas higher urinary norepinephrine and free T4 predicted future fat mass gain at 6 months (β = 3.0 kg per twofold difference in norepinephrine, P = 0.03; and β = 1.2 kg per 0.1-ng/dL difference in free T4, P = 0.03, respectively)., Conclusion: Lower SNS and free thyroid measurements at baseline indicate a greater capacity for CIBA, which may be predictive against fat mass gain.

In the hypothalamic arcuate nucleus (ARC), orexigenic agouti-related peptide (AgRP) neurons regulate feeding behavior and energy homeostasis. The 3-phosphoinositide-dependent protein kinase-1 (PDK1) in AgRP neurons serves as a major signaling molecule for leptin and insulin, the hormones regulating feeding behavior, energy homeostasis and circulation. However, it is unclear whether PDK1 in AGRP neurons is also involved in regulation of blood pressure. This study explored it by generating and analyzing AgRP neuron-specific PDK1 knockout (Agrp-Pdk1 flox/flox ) mice and effect of high salt diet on blood pressure in KO and WT mice was analyzed. Under high salt diet feeding, systolic blood pressure (SBP) of Agrp-Pdk1 flox/flox mice was significantly elevated compared to Agrp-Cre mice. When the high salt diet was switched to control low salt diet, SBP of Agrp-Pdk1 flox/flox mice returned to the basal level observed in Agrp-Cre mice within 1 week. In Agrp-Pdk1 flox/flox mice, urinary noradrenalin excretion and NUCB2 mRNA expression in hypothalamic paraventricular nucleus (PVN) were markedly upregulated. Moreover, silencing of NUCB2 in the PVN counteracted the rises in urinary noradrenalin excretions and SBP. These results demonstrate a novel role of PDK1 in AgRP neurons to counteract the high salt diet-induced hypertension by preventing hyperactivation of PVN nesfatin-1 neurons., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Preterm labor is an urgent medical-social and demographic issue at the present stage. A considerable number of factors affects the course of pregnancy and its outcome, their effect is realized at the level of the central nervous system through numerical metabolic interactions, where monoaminergic systems play an important role. Objective - to study the features of the sympathoadrenal system state by determining the excretion level of DOPHA, dopamine, norepinephrine and epinephrine in women's daily urine with different periods of abortion. 227 pregnant women who were admitted to the Kharkiv perinatal center have been examined, 190 of them had clinical signs of premature delivery in the gestation period of 23-36 weeks. Formation of clinical groups was carried out depending on the pregnancy term in the form of premature and timely delivery. Diagnosis of preterm labor was carried out in the presence of abdominal pain syndrome and structural changes in the cervix. Consequently, pregnancy compensatory and adaptive mechanisms are complex of neurohumoral process, which are realized through monoaminergic systems and a significant factor in its interruption is their destabilization. Reducing of sympathoadrenal system activity and reserve capacity in pregnant women may be a pathogenetic factor in the development of preterm labor. Therefore determination of the imbalance initial manifestations in the catecholamines exchange may possibly prevent the loss of pregnancy in the early stages.

Introduction : Major Depressive Disorder (MDD) is a common psychiatric disorder. Currently, there is no objective, cost-effective and non-invasive method to measure biological markers related to the pathogenesis of MDD. Previous studies primarily focused on urinary metabolite markers which are not proximal to the pathogenesis of MDD. Herein, we compare urinary monoamines, steroid hormones and the derived ratios amongst MDD when compared to healthy controls. Methods : Morning urine samples of medicated patients suffering from MDD ( n = 47) and healthy controls ( n = 41) were collected. Enzyme-linked immunosorbent assay (ELISA) was performed to measure five biomarkers: cortisol, dopamine, noradrenaline, serotonin and sulphate derivative of dehydroepiandrosterone (DHEAS). The mean urinary levels and derived ratios of monoamines and steroid hormones were compared between patients and controls to identify potential biomarkers. The receiver operative characteristic curve (ROC) analysis was conducted to evaluate the diagnostic performance of potential biomarkers. Results : Medicated patients with MDD showed significantly higher spot urine ratio of DHEAS/serotonin (1.56 vs. 1.19, p = 0.004) and lower ratio of serotonin/dopamine (599.71 vs. 888.60, p = 0.008) than healthy controls. A spot urine serotonin/dopamine ratio cut-off of >667.38 had a sensitivity of 73.2% and specificity of 51.1%. Conclusions : Our results suggest that spot urine serotonin/dopamine ratio can be used as an objective diagnostic method for adults with MDD.

Introduction: Resting energy expenditure (REE) increases after an intense exercise; however, little is known concerning mechanisms., Purpose: The purpose of this study was to determine effects of a single bout of moderate-intensity continuous (MIC) aerobic exercise, or high-intensity interval (HII) exercise on REE under energy balance conditions., Methods: Thirty-three untrained premenopausal women were evaluated at baseline, after 8-16 wk of training, 22 h after either MIC (50% peak V˙O2) or HII (84% peak V˙O2). Participants were in a room calorimeter during and after the exercise challenge. Food intake was adjusted to obtain energy balance across 23 h. REE was measured after 22 h after all conditions. Twenty-three-hour urine norepinephrine concentration and serum creatine kinase activity (CrKact) were obtained. Muscle biopsies were obtained in a subset of 15 participants to examine muscle mitochondrial state 2, 3, and 4 fat oxidation., Results: REE was increased 22 h after MIC (64 ± 119 kcal) and HII (103 ± 137 kcal). Markers of muscle damage (CrKact) increased after HII (9.6 ± 25.5 U·L) and MIC (22.2 ± 22.8 U·L), whereas sympathetic tone (urine norepinephrine) increased after HII (1.1 ± 10.6 ng·mg). Uncoupled phosphorylation (states 2 and 4) fat oxidation were related to REE (r = 0.65 and r = 0.55, respectively); however, neither state 2 nor state 4 fat oxidation increased after MIC or HII. REE was not increased after 8 wk of aerobic training when exercise was restrained for 60 h., Conclusions: Under energy balance conditions, REE increased 22 h after both moderate-intensity and high-intensity exercise. Exercise-induced muscle damage/repair and increased sympathetic tone may contribute to increased REE, whereas uncoupled phosphorylation does not. These results suggest that moderate- to high-intensity exercise may be valuable for increasing energy expenditure for at least 22 h after the exercise.

Background: Glucocorticoids influence the synthesis and metabolism of catecholamines (epinephrine and norepinephrine) and metanephrines (metanephrine and normetanephrine). The aim of this study was to measure urinary catecholamines and metanephrines in dogs with hypercortisolism before and during trilostane therapy. Urine samples were collected during initial work up and during therapy with trilostane in 14 dogs with hypercortisolism and in 25 healthy dogs. Epinephrine, norepinephrine, metanephrine and normetanephrine were measured using high-pressure liquid chromatography and expressed as ratios to urinary creatinine concentration., Results: Untreated dogs with hypercortisolism had significantly higher epinephrine, norepinephrine, and normetanephrine:creatinine ratios compared to healthy dogs. During trilostane therapy, urinary catecholamines and their metabolites did not decrease significantly. However, dogs with low post-ACTH cortisol concentrations during trilostane therapy had less increased epinephrine, norepinephrine and normetanephrine:creatinine ratios compared to healthy dogs. There was no correlation of urinary catecholamines and their metabolites with baseline or post-ACTH cortisol or endogenous ACTH concentrations during trilostane therapy., Conclusion: Influences between steroid hormones and catecholamines seem to occur, as dogs with hypercortisolism have significantly higher urinary epinephrine, norepinephrine, and normetanephrine:creatinine ratios. Once-daily trilostane therapy does not lead to a significant decrease in catecholamines and their metabolites. Trilostane-treated dogs still have increased urinary epinephrine, norepinephrine and normetanephrine:creatinine ratios during trilostane therapy.

Background: Adaptive servoventilation (ASV) is a new therapeutic modality to treat sleep-disordered breathing (SDB) especially for central sleep apnoea associated with Cheyne-Stokes respiration, whereas the role of ASV in SDB patients with heart failure (HF) is controversial. The purpose of this study was to evaluate the effects of ASV on these patients through a meta-analysis of published data., Methods: A comprehensive literature search was performed to identify studies focused on ASV through databases, including PubMed, Medline, Embase, Cochrane Library and Web of science from 1950 to 2014. Parallel randomised controlled trials which compared ASV to other controls in HF and SDB patients with extractable data were meet our inclusion criteria. Random effects meta-analysis models were applied using RevMan 5.2., Results: Seven studies involving 301 patients were recruited in the meta-analysis. The weighted mean difference in apnoea hyponea index (-17.73 events/h, 95% CI, -21.85 to -2.94) and left ventricular ejection fraction (MD: 4.68, 95% CI, 2.74-6.63) both favored ASV compared to control conditions. The urinary noradrenaline level (MD: -32.18, 95%CI: -44.07 to -20.09) was decreased, while the exercise capacity measured by 6-min walk distance (MD: 41.26, 95% CI, 17.06-65.45) was improved after ASV treatment. Whereas neither left ventricular end-diastolic diameter (LVEDD) nor Epworth sleepiness-scale score (ESS) significantly changed after ASV therapy., Conclusions: ASV is superior to other therapy, as it can result in good consequences for patients with SDB and improve their prognosis in cardiac function. Further studies will still be needed to assess the benefit of it., (© 2015 John Wiley & Sons Ltd.)

Background: Hypertension is a major cause of heart failure. Excessive sympathoexcitation in patients with heart failure leads to poor prognosis. Since carotid body denervation (CBD) has been shown to reduce sympathetic nerve activity in animal models of hypertension and heart failure, we examined if bilateral CBD attenuates the progression of hypertensive heart failure and improves survival., Methods: We randomly allocated Dahl salt-sensitive rats fed a high-salt diet from 6 weeks of age into CBD (n = 31) and sham-operation (SHAM; n = 50) groups, and conducted CBD or SHAM at 7 weeks of age. We examined the time course of 24-hour urinary norepinephrine (uNE) excretion, blood pressure (BP) and the percent fractional shortening assessed by echocardiography, and estimated the pressure-natriuresis relationship at 14 weeks of age. Finally, we assessed hemodynamics, histological findings, and survival at 16 weeks of age., Results: Compared to SHAM, CBD significantly reduced 24-hour uNE at 12, 14, and 16 weeks of age, shifted the pressure-natriuresis relationship leftward without changing its slope, and attenuated the increase in BP. CBD preserved percent fractional shortening (34.2 ± 1.2 vs. 29.1 ± 1.3%, P < 0.01) and lowered left ventricular end-diastolic pressure (5.0 ± 0.9 vs. 9.0 ± 1.4 mm Hg, P < 0.05). Furthermore, CBD significantly attenuated myocardial hypertrophy (P < 0.01) and fibrosis (P < 0.01). Consequently, CBD markedly improved survival (relative risk reduction: 64.8%)., Conclusions: CBD attenuated the progression of hypertension and worsening of heart failure possibly through sympathoinhibition, and markedly improved survival in a rat model of hypertensive heart failure., (© American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC) remains an elusive disease with the cause for the pain unclear. BPS/IC patients present increased sympathetic activity and high levels of urinary noradrenaline. At the experimental level, it has been shown that chronic adrenergic stimulation produces pain and bladder changes through an alpha 1A adrenoceptor mediated mechanism. Water avoidance stress (WAS) in rodents reproduces signs of nociception and bladder changes seen in BPS/IC patients. In this study, we explore the possible role of alpha 1A adrenoceptor in bladder pain and morphological changes. WAS was induced in a group of female Wistar rats. A separate WAS group received 0.2 mg/kg day silodosin (WAS + S). Lower abdominal pain was determined by performing sensitivity to Von Frey filaments. Bladder reflex activity was determined by cystometry in anaesthetised animals. Urine was collected for noradrenaline quantification by HPLC. Bladders were harvested and stained with Haematoxylin-eosin (to analyse urothelial morphology and to determine the disruption of surface umbrella cells) or with Toluidine Blue 0.1% to analyse mast cell infiltration. WAS increased urinary noradrenaline level and bladder frequency and decreased mechanical pain threshold, which was reversed by silodosin. WAS induced lymphocytic and mast cells infiltration in the mucosa and mild urothelial disruption, which was absent in WAS + S group. Alpha 1A adrenoceptor stimulation has an important role in the appearance of bladder pain in rats. Since BPS/IC patients present high levels of noradrenaline, alpha 1A stimulation may be an additional trigger for bladder dysfunction presented by these patients. Further studies will determine the clinical relevance of this finding in the treatment of BPS/IC patients.