Higher Norepinephrine Levels Research Articles

6891 Exclusive Normetanephrine Secreting Pheochromocytoma In A Young Male

Abstract Disclosure: E. Askar: None. H. Moran: None. IntroductionPheochromocytomas and paragangliomas arise from chromaffin cells and produce excessive catecholamines. Hypertension is their primary clinical symptom. they differ in their catecholamine secretory phenotype; paragangliomas typically secrete norepinephrine, while pheochromocytomas typically secrete epinephrine. Here, we present a case 21-year-old male with pheochromocytoma with elevated norepinephrine but normal epinephrine levels.Case presentationA 21 -year-old male with no past medical history presented with episodes of palpitations, sweating, and elevated blood pressure. He also reported abdominal pain. On admission, his blood pressure was 143/92 mmHg, pulse was 71/min, respiration was 16/min, and oxygen saturation was 100% in room air. The rest of physical exam was not significant. His electrolyte panel was normal. Computed tomography (CT) abdomen and pelvis with contrast was performed and showed a right adrenal mass measuring 4.9 x 4.0 x 6.5 cm which is predominantly hypoattenuating (approximately 30 Hounsfield units) with thick nodular rim of enhancement. Hormonal workup showed normal serum testosterone, DHEA-S, AM cortisol, ACTH, aldosterone, plasma metanephrine, and urine metanephrine, but profoundly high plasma normetanephrine 3641.6 (0.0-210.1) pg/mL. His 24-hour urinary normetanephrine was elevated at 14874 (80-440) ug/24hr, confirming a pheochromocytoma. The high norepinephrine level in the setting of normal epinephrine raised suspicion for Von Hippel Lindau (VHL). He was started on alpha and beta blockage and had laparoscopic removal of the right adrenal gland. The pathology report confirmed the diagnosis of pheochromocytoma confined to right adrenal. The patient was then referred for genetic testing. Conclusion: Pheochromocytoma can be a part of familial disorders, although being sporadic in nature most of the time. As demonstrated in our case, the hallmark of pheochromocytoma associated with VHL is nearly exclusive normetanephrine secretion and a high ratio of normetanephrine to metanephrine. Confirmation and testing of genes aid in proper monitoring and follow-up. The preferred course of treatment is radical resection. Presentation: 6/2/2024

Norepinephrine Reuptake Inhibition, an Emergent Treatment for Neurogenic Orthostatic Hypotension.

The NET (norepinephrine transporter) is situated in the prejunctional plasma membrane of noradrenergic neurons. It is responsible for >90% of the norepinephrine uptake that is released in the autonomic neuroeffector junction. Inhibitors of this cell membrane transporter, known as norepinephrine reuptake inhibitors (NRIs), are commercially available for the treatment of depression and attention deficit hyperactivity disorder. These agents increase norepinephrine levels, potentiating its action in preganglionic and postganglionic adrenergic neurons, the latter through activation of α-1 adrenoreceptors. Previous studies found that patients with neurogenic orthostatic hypotension can improve standing blood pressure and reduce symptoms of neurogenic orthostatic hypotension after a single administration of the selective NRI atomoxetine. This effect was primarily observed in patients with impaired central autonomic pathways with otherwise normal postganglionic sympathetic fibers, known as multiple system atrophy. Likewise, patients with normal or high norepinephrine levels may benefit from NRIs. The long-term efficacy of NRIs for the treatment of neurogenic orthostatic hypotension-related symptoms is currently under investigation. In summary, an in-depth understanding of the pathophysiology of neurogenic orthostatic hypotension resulted in the discovery of a new therapeutic pathway targeted by NRI.

The emotion paradox in the aging body and brain.

With age, parasympathetic activity decreases, while sympathetic activity increases. Thus, the typical older adult has low heart rate variability (HRV) and high noradrenaline levels. Younger adults with this physiological profile tend to be unhappy and stressed. Yet, with age, emotional experience tends to improve. Why does older adults' emotional well-being not suffer as their HRV decreases? To address this apparent paradox, I present the autonomic compensation model. In this model, failing organs, the initial phases of Alzheimer's pathology, and other age-related diseases trigger noradrenergic hyperactivity. To compensate, older brains increase autonomic regulatory activity in the pregenual prefrontal cortex (PFC). Age-related declines in nerve conduction reduce the ability of the pregenual PFC to reduce hyperactive noradrenergic activity and increase peripheral HRV. But these pregenual PFC autonomic compensation efforts have a significant impact in the brain, where they bias processing in favor of stimuli that tend to increase parasympathetic activity (e.g., stimuli that increase feelings of safety) and against stimuli that tend to increase sympathetic activity (e.g., threatening stimuli). In summary, the autonomic compensation model posits that age-related chronic sympathetic/noradrenergic hyperactivity stimulates regulatory attempts that have the side effect of enhancing emotional well-being.

Assotiation of testosterone levels and oxidative stress activity with 10-year survival in men with cardiac resynchronization therapy

Aim. To investigate the association of testosterone levels (TES) and oxidative stress activity with 10-year survival in men with cardiac resynchronization therapy (CRT).Methods. 86 men with CRT (59.0±9.8 years; 66.3% ischemic cardiomyopathy) were divided into 4 groups: Gr.1 (n=19) TES<median level (16.4nmol/l) + myeloperoxidase (MPO) < median level (32.5 ng/mL); Gr.2 (n=18) TES<median level + MPO>median level; Gr.3 (n=23) TES> medians + MPO < median level; Gr.4 (n=26) TES > median level + MPO > median level. Echocardiography parameters, incidence of ventricular extrasystole, TES in plasma, estradiol, progesterone, dehydroepiandrosterone sulfate, norepinephrine, MPO, NT-proBNP, matrix metalloproteinase, tissue inhibitor of metalloproteinase were assessed. Prognostic level of NT-proBNP was assessed by ROC analysis; 10-year survival was measured by Kaplan-Meier method, factors associated with it were evaluated using Cox regression.Results. The majority of patients were NYHA II and NYHA III for Gr. 3 and Gr.4 respectively (р3-4=0,010). At baseline: there was no difference in echocardiography parameters, levels of NT-proBNP, MPO, steroids, matrix metalloproteinase between groups; tissue inhibitor of metalloproteinase was higher in Gr.2 and Gr.4; the highest norepinephrine levels was in Gr.4. Follow-up: reverse cardiac remodeling was associated with NT-proBNP decreasing and was registered in Gr.4 and Gr. 3. The level of MPO was decreased in Gr.3, Gr.4., and was the highest in Gr.4. The level of estradiol was increased in Gr.1; There were no difference in hormone levels in Gr.2. TES, dehydroepiandrosterone sulfate was increased, but progesterone was decreased in Gr.3 and in Gr.4. The norepinephrine`s levels were increased in all groups. The number of ventricular extrastimuli was increased in Gr.4. Predictive level of NT-proBNP was 756.0 pg/ml (AUC=0.685; p=0.003; sensitivity: 64%, specificity: 68%). The 10-year survival rate was 15.4%; 33.5%; 76.3%; 24.4% for Gr. 1-4 respectively (Log Rank test: Gr.1-2=0.378; Gr.1-3<0.001; Gr.1-4=0.070; Gr.2-3=0.009; Gr.2-4=0.772; Gr.3-4=0.010). The survivance was higher in patients with the best CRT response time (p=0.004), the level of NT-proBNP>756.0 pg/ml (p=0.001) in Gr.1, Gr.2; the best CRT response time (p=0.001), left ventricular ejection fraction (p=0.046), MPO>median (p=0.041), amiodarone administration (0.008) in Gr. 3, Gr. 4.Conclusion. CRT modulates steroidogenesis. Increase of TES and dehydroepiandrosterone sulfate with lower oxidative stress activity is associated with greater reverse cardiac remodeling and better 10-year survival rate. The higher level of TES and simultaneously MPO more than 32.5 pg/ml were related to less reverse cardiac remodeling, higher rate of amiodarone administration by 5.2 times, increasment of ventricular arrhythmias rate and higher relative risk of death by 4.2 times. Relationship between 10-year survival rate and period of best CRT response indicates less physiological nature of forceful modulating effects of CRT.

Анализ содержания катехоламинов и параметров липидного обмена у аборигенного и местного европеоидного населения Арктической зоны Российской Федерации

The study of fat metabolism and the levels of sympathoadrenal hormones in the indigenous population of the Arctic presently changing their lifestyle from nomadic to sedentary is undoubtedly of practical interest. The purpose of this article was to conduct a comparative analysis of the content of catecholamines, triglycerides and saturated fatty acids in the inhabitants of the Arctic zone of the Russian Federation, depending on their lifestyle (nomadic indigenous people, sedentary indigenous people, and local Russian population), age and sex. Materials and methods. The study involved 472 subjects: men and women of the first (men: 22–35 years old; women: 21–35 years old) and second (men: 36–60 years old; women: 36–55 years old) periods of adulthood, leading different lifestyles. The following were determined in the blood serum: triglyceride concentrations using the enzymatic method; level of saturated fatty acids (ƩSFA) using gas-liquid chromatography, followed by а calculation of the content of short-, medium- and long-chain saturated fatty acids (ƩSCFA, ƩMCFA, ƩLCFA). Urine levels of adrenaline and noradrenaline were determined by means of fluorimetry. Results. Regardless of their lifestyle, adult subjects, primarily women, showed high adrenaline values, low triglyceride concentrations and elevated ƩSFA. Correlation analysis established a negative association of adrenaline with ƩLCFA and ƩSFA in sedentary indigenous women aged 21–35 years and with ƩMCFA in those aged 36–55 years. In local Russian women aged 36–55 years, on the contrary, a positive association of noradrenaline with ƩSCFA, ƩMCFA, ƩLCFA and ƩSFA was found. No statistically significant correlations were identified in nomadic indigenous women. Unlike women, men had a correlation between adrenaline content and ƩMCFA only among local Russians: negative in 22–35-year-olds and positive in 36–60-year-olds with high noradrenaline levels. On the one hand, low triglyceride values and elevated ƩSFA among residents of the Arctic zone of the Russian Federation maintain the energy homeostasis of the body. On the other hand, they lead to overweight and obesity, which increases the risk of new-onset metabolic dysfunction-associated diseases, especially in women.

Multi-Organ Increase in Norepinephrine Levels after Central Leptin Administration and Diet-Induced Obesity.

Autonomic innervation is important to regulate homeostasis in every organ of the body. The sympathetic nervous system controls several organs associated with metabolism and reproduction, including adipose tissue, the liver, and the ovaries. The sympathetic nervous system is controlled within the central nervous system by neurons located in the hypothalamus, which in turn are regulated by hormones like leptin. Leptin action in the hypothalamus leads to increased sympathetic activity in the adipose tissue. In this short report, we propose that leptin action in the brain also controls the sympathetic innervation of other organs like the liver and the ovary. We performed two experiments: We performed an intracerebroventricular (ICV) injection of leptin and measured norepinephrine levels in several organs, and we used a validated model of overnutrition and obesity to evaluate whether an increase in leptin levels coexists with high levels of norepinephrine in the liver and ovaries. Norepinephrine was measured by ELISA in adipose tissue and by HPLC-EC in other tissues. Leptin was measured by ELISA. We found that the ICV injection of leptin increases norepinephrine levels in several organs, including the liver and ovaries. Also, we found that diet-induced obesity leads to an increase in leptin levels while inducing an increase in norepinephrine levels in the liver and ovaries. Finally, since hyperactivity of the sympathetic nervous system is observed both in non-alcoholic fatty liver disease and polycystic ovary syndrome, we think that an increase in norepinephrine levels induced by hyperleptinemia could be involved in the pathogenesis of both diseases.

High Norepinephrine State Induces Growth of Colorectal Cancer Cells via ADP-Ribosyltransferase 1 in Type 2 Diabetes Mellitus.

Patients with type 2 diabetes mellitus have a higher susceptibility for colorectal cancer and poorer prognosis, but the mechanism is still unknown. Here, we investigated the effect of ADP-ribosyltransferase 1 (ART1) on the growth of colorectal cancer in an animal model of diabetes with high norepinephrine status, as well as the potential mechanism. We evaluated the size and weight of transplanted CT26 cell tumors with different ART1 expression levels in a mouse model of diabetes, as well as the survival time. CCK8 and flow cytometry were used to evaluate the growth of CT26 cells in vitro. Western blot was performed to analyze differentially expressed proteins in the ART1-modulated pathway. High levels of norepinephrine and ART1 favored the proliferation of CT26 cells in vitro and in vivo. Moreover, inhibition of norepinephrine-dependent proliferation was observed in ART1-silenced CT26 cells compared to those with normal ART1 expression. Following reduction of the serum norepinephrine level by surgery, the size and weight of transplanted CT26 cell tumors was significantly reduced compared to non-operated and sham-operated mice. Furthermore, the expression of ART1, mTOR, STAT3, and p-AKT protein in the tumor tissue of diabetic mice was higher than in non-diabetic mice. Following reduction of the norepinephrine level by renal denervation (RD), expression of the proliferation-related proteins mTOR, STAT3, p-AKT protein decreased, but no change was seen for ART1 expression. At the same concentration of norepinephrine, ART1 induced the expression of p-AKT, mTOR, STAT3, CyclinD1 and c-myc in CT26 cells in vitro. We conclude that faster growth of colorectal cancer in high norepinephrine conditions requires the expression of ART1, and that high ART1 expression may be a novel target for the treatment of diabetes-associated colorectal cancer.

Blunted Glucocorticoid Responsiveness to Stress Causes Behavioral and Biological Alterations That Lead to Posttraumatic Stress Disorder Vulnerability

BackgroundUnderstanding why only a subset of trauma-exposed individuals develop posttraumatic stress disorder is critical for advancing clinical strategies. A few behavioral (deficits in fear extinction) and biological (blunted glucocorticoid levels, small hippocampal size, and rapid-eye-movement sleep [REMS] disturbances) traits have been identified as potential vulnerability factors. However, whether and to what extent these traits are interrelated and whether one of them could causally engender the others are not known. MethodsIn a genetically selected rat model of reduced corticosterone responsiveness to stress, we explored posttraumatic stress disorder–related biobehavioral traits using ex vivo magnetic resonance imaging, cued fear conditioning, and polysomnographic recordings combined with in vivo photometric measurements. ResultsWe showed that genetic selection for blunted glucocorticoid responsiveness led to a correlated multitrait response, including impaired fear extinction (observed in males but not in females), small hippocampal volume, and REMS disturbances, supporting their interrelatedness. Fear extinction deficits and concomitant disruptions in REMS could be normalized through postextinction corticosterone administration, causally implicating glucocorticoid deficiency in two core posttraumatic stress disorder–related risk factors and manifestations. Furthermore, reduced REMS was accompanied by higher norepinephrine levels in the hippocampal dentate gyrus that were also reversed by postextinction corticosterone treatment. ConclusionsOur results indicate a predominant role for glucocorticoid deficiency over the contribution of reduced hippocampal volume in engendering both REMS alterations and associated deficits in fear extinction consolidation, and they causally implicate blunted glucocorticoids in sustaining neurophysiological disturbances that lead to fear extinction deficits.

Observed Causal Relationship Between Eczema and Inflammatory Bowel Diseases

Over the past 27 years in my functional medicine clinical practice, I have had 10 or more patients present with chronic and acute cases of eczema. After taking a thorough history, ordering blood tests and food intolerance panels, all of them were positive for signs and symptoms of intestinal permeability and positive IgA markers to predominantly; gliadin, agglutinins and casein, as well as a plethora of other food proteins, due to the nature of molecular mimicry. After placing patients on an antigen free food plan for 3-6 months, prescribing demulcent herbals, L-glutamine, anti-inflammatory supplements, and counseling them on stress reducing strategies, there was a resolution of the eczema and a healing of the intestinal lining. There is a misconception in traditional allopathic medicine that the problem resides at the dermis, where the symptomatology is observed and expressed. However, the skin is just a reflection and extension of the inflammatory cascade occurring at the intestinal lining which leads to the erosion of the tight junctions of the microvilli, which causes intestinal permeability [1,2]. These erosions open the door to undigested proteins which end up in the enteric blood vessels, subsequently triggering white blood cells to tag these proteins with antibodies. These proteins are almost identical to body tissues (molecular mimicry) , leading to autoimmune reactivity. Eczema is a direct expression of this immune system response and loss of oral and self-tolerance. The road to healing the tight junctions begins with an elimination food plan that excludes all the proteins which have become antigens. I have found it necessary to prescribe demulcent herbs such as; slippery elm, aloe vera gel, marshmallow root, deglycyrrhizinated licorice, rhubarb, immunoglobulin compounds, turmeric, vitamin D3/K2, glutathione, resveratrol and omega 3’s, as well as counseling patients on stress reduction strategies, given that production of high levels of cortisol and norepinephrine contribute to erosion of tight junctions [3]. The more a patient unburdens their body from causative factors, the faster the transformation and quicker the necessary scaffolding is built, to provide significant symptom relief and restoration of functional physiological processes that render a vital healthy human being, who is capable of developing immune and chemical tolerance to living in this “modern” hectic world. We live in a world where we spend 80% of our daily lives running from the “tyrannical lion(ness)” inside our busy monkey minds. In “flight or fight mode”, we are running tons of adrenaline epinephrine, norepinephrine, putting out fires, disasters, unknowns, daily to-do lists, answering phone calls, typing on the computer, driving around freeways, and encountering angry, impatient beings along the way. We are also near-constantly bombarded by lights, sounds, smells, EMF’s, microwaves, 4G and now the 5G radiation grid, toxins, infections, and stressors of all kinds [4]. Taking time to counter these daunting and relentless “flight or fight” drivers is imperative if we are to survive as beings and as a collective species. Stimulating your parasympathetic nervous system is a MUST when leading patients towards successful restoration of health and wellness.

Blood concentrations of brain natriuretic peptide (Nt-pro-BNP) and the regulation of hemodynamic reactions in healthy adult Arctic residents

BACKGROUND: In previous studies, we have observed that the levels of Nt-pro-BNP in healthy individuals are lower than among patients with coronary heart disease and hypertension. Additionally, Nt-pro-BNP concentration increases with age. Interestingly, Arctic residents have higher levels of Nt-pro-BNP compared to those living in other northern territories.
 AIM: To study the role of Nt-pro-BNP in the regulation of hemodynamic reactions in adults residing in the Arctic.
 MATERIALS AND METHODS: In total, 111 healthy adults (66 women and 45 men) aged 4655 years living and working on Svalbard, and in the Murmansk region comprised the study group. The comparison group included 118 healthy adults of the same age from the Arkhangelsk region (59 women and 59 men). Peripheral venous blood samples were taken. Hemogram and concentrations of CD3+, CD4+, CD8+, CD10+, CD16+, CD19+, CD23+, CD25+, CD71+ lymphocytes were studied by an indirect immunoperoxidase reaction and a flow cytometry. Blood concentrations of Nt-pro-BNP, endothelin-1, total NO, endogenous NO2, nitrate NO3, cortisol, norepinephrine, epinephrine were assessed using enzyme immunoassay. Data were presented as means and standard errors of the mean (Mm). Depending on the distribution, unpaired t-tests or MannWhitney U-tests were used for all comparisons.
 RESULTS: Blood concentration of Nt-pro-BNP was higher in the Arctic residents compared with those living in Arkhangelsk. Elevated concentrations of Nt-pro-BNP in the Arctic residents were associated with higher levels of norepinephrine and cortisol and lower concentrations of epinephrine and endothelin-1. Moreover, we observed a re-distribution of lymphocytes and monocytes from the circulating to the marginal pool. These features of the hemodynamic reaction were more pronounced among the Arctic residents and among women in all settings.
 CONCLUSION: The effect of natriuretic peptide is associated with simultaneous activation of the concurrent activation of norepinephrine and cortisol secretion, which poses a risk of disrupting the body's mechanisms for maintaining a narrow range of osmolarity in the internal environment.

Genetic Study in Pheochromocytoma: Is It Possible to Stratify the Risk of Hereditary Pheochromocytoma?

Introduction: It is estimated that 30–40% of patients with apparently sporadic pheochromocytomas (PHEOs) have an inherited predisposition syndrome. The aim of our study was to develop a predictive model of hereditary PHEO based on the clinical, hormonal, and radiological features present at the diagnosis of patients with PHEOs. Methods: A retrospective multicenter cohort study of patients with PHEOs with available genetic study from 18 tertiary hospitals. Clinical, biochemical, and radiological features were used to build a multivariate logistic regression model. The estimation of all possible equations was used to select the model with the best diagnostic accuracy (lower Akaike index). Results: A total of 245 patients were included: 169 (69.0%) patients with sporadic PHEOs and 76 (31%) with hereditary PHEOs. The parsimonious predictive model with the highest diagnostic accuracy for the prediction of hereditary PHEO combined the variables age, non-cardiovascular disease, urinary norepinephrine levels, and tumor size. The area under the ROC curve of this model was 0.800 (0.705–0.887). Based on the predictive model, the probability of hereditary PHEO in patients older than 60 years with cardiovascular disease, high levels of urinary norepinephrine and unilateral PHEOs >60 mm was <2%. And if the age was above 80 years, lower than 1%. The probability of sporadic PHEO linearly increased with age (MH Test for linear Trend: χ2 (1) = 30.05; p < 0.001). Conclusion: In certain populations such as old patients with cardiovascular disease, with high levels of urinary norepinephrine and large tumors in which the probability of hereditary PHEO is very low, genetic testing could be avoided in the absence of specific suspicion.

Acute and protocol-dependent effects of aerobic exercise on neurobiochemical indices and neuropsychological performance of working memory

This study aimed to clarify the effects of high-intensity interval exercise (HIIE) and moderate-intensity continuous exercise (MICE) protocols on peripheral neurotransmitters and on the neuropsychological performance of working memory and to explore underlying correlations. In a randomised cross-over trial, twenty-two adults in late middle age or older completed a single session of HIIE, MICE, or a control condition (rest) in counterbalanced order with a 7-day washout. Neuropsychological indices of working memory and neurotransmitter (norepinephrine, dopamine, and serotonin) levels were measured at baseline and after an intense bout of either HIIE or MICE, or an intervention without exercise. Analyses of the results revealed no significant effect of HIIE on the neurotransmitters, but significantly high levels of norepinephrine and serotonin were induced by MICE. In terms of neuropsychological performance, a single session of HIIE and MICE shortened the participants' reaction times (RTs), whereas only MICE caused a significant increase in accuracy rates (ARs). Significant correlations were found between the changes in norepinephrine levels and ARs/RTs before and after the HIIE and MICE interventions, respectively. The results of this study suggest that an intense MICE protocol triggers higher norepinephrine and serotonin levels than HIIE does. The possible neurobiochemical factor (i.e., norepinephrine) underlying the HIIE/MICE-induced neuropsychological benefits (i.e., improved ARs and RTs) for working memory encoding and maintenance appears to be protocol-dependent. Systematic and prolonged investigations are required to further understand the effects/mechanisms specific to each exercise protocol in order to optimize the benefits of aerobic exercise interventions for long-term neurobiochemical and neuropsychological health.

Abstract 13157: Workplace Culture and Biomarkers of Sympathetic Activation

Workplace environment can impact health, but most research has focused on toxic chemicals. Recently, workplace culture—experiences, values, and behaviors unique to a workplace—is studied for its impact on overall health risk; however, connections with robust biologic markers of health remain to be established. Therefore, we examine associations between work environment and urinary levels of catecholamines and their metabolites as biomarkers of sympathetic activation. In 2018-19, we recruited participants (n=219) from an ongoing CV risk cohort to investigate workplace culture, overall well-being, and stress. Participants completed 7 questionnaires. Clean catch urine samples were used to measure catecholamines and their metabolites. To estimate associations between work and health scales and log or logit-transformed outcomes we used Pearson correlation and linear regression models adjusting for demographics and creatinine. Participants reporting higher well-being had lower levels of dopamine (DA) ( r = -0.28), serotonin (5HT) ( r = -0.17), and 3-methoxytyramine (3MT) ( r = -0.31), a product of dopamine breakdown. Participants reporting a more engaged workplace had lower levels of DA ( r = -0.20) and 3MT ( r = -0.22). Those reporting more positive workplace culture had lower levels of DA ( r = -0.17) and 3MT ( r = -0.26) and higher levels of norepinephrine ( r = 0.19) and 5-hydroxyindole-3-acetic acid (HIAA) ( r = 0.22). When participants identified more workplace isolation, they had higher levels of DA ( r = 0.19) and 3MT ( r = 0.19). Positive workplace culture was correlated with lower levels of DA ( r = -0.22) and 3MT ( r = -0.28) and higher levels of HIAA ( r = 0.22) and homovanillic acid ( r = 0.20). Given high correlations between catecholamines, we used 3MT for linear regression. In fully adjusted models we found in more positive work cultures, levels of 3MT remained significantly lower (β = -0.065 ±0.025, p = 0.01), accounting for 23% of the variance, and a significant positive association between workplace isolation and 3MT (β= 0.064 ±0.030, p = 0.04), accounting for 22% of the variance with 3MT, which may reflect greater dopamine degradation. These findings suggest an important relationship between how we work and sympathetic nervous system activity.

Mutational Profile and Potential Molecular Therapeutic Targets of Pheochromocytoma.

PurposePheochromocytoma/paraganglioma (PCC/PGL; collectively known as PPGL) can be driven by germline and somatic mutations in susceptibility genes. We aimed to investigate the mutation profile and clinical features of pathogenic genes in highly genetically heterogeneous PPGL and to preliminary explore molecular therapeutic targets in PPGL.MethodsWe established a panel of 260 genes, including susceptibility genes of PPGL and other important tumorigenic genes to sequence 107 PPGL tissues.ResultsOverall, 608 genomic mutations were identified in 107 PPGL tissues. Almost 57% of PPGL tissue samples exhibited pathogenic mutations, and the most frequently mutated gene was SDHB (15/107, 14%). SDHB and HRAS were the most commonly mutated genes in germline-mutated PPGL (25/107, 23%) and nongermline-mutated PPGL (36/107, 34%), respectively. In addition, novel pathogenic mutations were detected in sporadic PPGL. PPGL with mutations in the hypoxia pathway had an earlier onset and higher norepinephrine level than those in the kinase pathway. Receptor tyrosine kinase (RTK; 22%, 24/107), mitogen-activated protein kinase (MAPK; 14%, 15/107), and tyrosine kinase (TK; 2%, 2/107) pathways were the most frequently mutated pathways in PPGL.ConclusionOur results provided the genetic mutation profile in PPGL tissues. Genetic mutations in PPGL were mainly concentrated in the RTK, TK, and MAPK pathways, suggesting potential molecular therapeutic targets for PPGL.

Management of Medication-Induced Psychiatric Disorders.

Management of Medication-Induced Psychiatric Disorders.

Treadmill running alleviates adipose tissue browning and lipolysis in rats with heart failure.

This study observed the effects of treadmill running on adipose tissue browning and lipolysis in rats with induced heart failure and elucidated the possible mechanism. Rats underwent abdominal aortic constriction as a model of heart failure. Cardiac function was detected by echocardiography. We detected serum levels of norepinephrine and interleukin 6, cardiac atrial natriuretic peptide and brain natriuretic peptide and marker genes of browning, white adipose tissue (WAT), and lipolysis in adipose tissue. Rats with heart failure showed typical symptoms such as increased heart weight and mRNA levels of atrial natriuretic peptide and brain natriuretic peptide and decreased left ventricular ejection fraction. Exercise partially improved left ventricular diastolic function and significantly decreased atrial natriuretic peptide expression. Rats with heart failure showed significantly reduced body weight and ratios of muscle and fat weight to body weight. Exercise significantly increased body weight and the ratio of muscle weight to body weight. Heart failure stimulated the expression of proliferator-activated receptor-gamma coactivator-1-alpha and uncoupling protein 1 in epididymal WAT, inguinal WAT, and brown adipose tissue but decreased that of adiponectin and leptin in inguinal WAT. Lipolysis, characterized by high adipose triglyceride lipase and hormone-sensitive lipase expression, was activated in all adipose tissues. Exercise reduced browning and lipolysis in adipose tissues. Rats with heart failure had abnormally high levels of serum norepinephrine and interleukin 6, which could be suppressed by exercise. Exercise may improve cardiac cachexia and inhibit the browning and lipolysis of adipose tissue by downregulating sympathetic nervous system activity and inflammation.

A commentary of “Stress turns hair white”: 10 remarkable discoveries from 2020 in Nature

This was the “News & Views” story in the journal Nature that was most popular online in 2020. The relative contribution of stress to greying of the hair is not known. Hair color is determined by melanocyte cells derived from melanocyte stem cells (MeSCs) located in a part of the hair follicle called the bulge. This paper, published in Nature in January 2020, was authored by Ya-Chieh Hsu's research group at Harvard University, with Bing Zhang as the first author [1]. Zhang et al. report that noradrenaline - a neurotransmitter molecule involved in the “fight or flight” response to stress — is released from neurons of the sympathetic nervous system. MeSC proliferation and differentiation increase markedly under extreme stress or on exposure to a high level of noradrenaline, resulting in a mass migration of melanocytes away from the bulge and leaving no remaining stem cells to replace them,① thus causing greying. This work by Zhang et al. provides a better understanding of how stress influences other stem cells as well as clues for finding ways to stop and reverse the effects of stress.①①Original source in Chinese: Ji Hu, Stress turns hair white, Bulletin of National Natural Science Foundation of China. 35 (2) (2021) 247-248

Effects of Short-Term Golden Root Extract (Rhodiola rosea) Supplementation on Resistance Exercise Performance.

The purpose of this study was to examine the effects of short-term Golden Root Extract (GRE; Rhodiola rosea) supplementation on blood lactate, catecholamines, and performance during repeated bench press exercise. Resistance-trained males (n = 10) participated in this study. In a double-blinded, crossover, counterbalanced study design, participants supplemented with either 1500 mg/day of GRE or placebo (PL; gluten-free cornstarch) for 3 days prior to experimentation. An additional 500 mg dose was ingested 30 min prior to exercise testing. During each exercise trial, participants completed 2 repetitions of bench press at 75% of one-repetition maximum (1RM) as explosively as possible. A linear position transducer was used to measure mean concentric velocity. After 5 min of rest, participants completed 3 sets × repetitions to failure (RTF) at 75% 1RM separated by 2 min of rest between each set. A capillary blood sample was obtained pre- (PRE) and immediately post- (POST) exercise to measure blood concentrations lactate (LA), epinephrine (EPI), and norepinephrine (NE). Mean concentric velocity was significantly higher with GRE when compared to PL (p = 0.046). However, total RTF were significantly lower with GRE versus PL (p < 0.001). Regardless of treatment, LA was significantly higher Post versus Pre (p < 0.001), but GRE resulted in greater Post values compared to PL (p = 0.049). EPI and NE increased in both conditions Pre to Post (p < 0.001). However, Pre NE was significantly higher with GRE versus PL (p = 0.008). Findings indicate that short-term GRE supplementation increases mean bench press velocity but decreases bench press repetition volume. Furthermore, GRE resulted in higher NE levels and blood lactate following exercise. Thus, supplementing with GRE may enhance explosive resistance training performance but may also impair upper body strength-endurance.

Norepinephrine Enhances Aerobic Glycolysis and May Act as a Predictive Factor for Immunotherapy in Gastric Cancer.

Methods Monoamine neurotransmitters were detected in gastric cancer tissue and paired normal tissue, and The Cancer Genome Atlas was used to identify differentially expressed norepinephrine-degrading and synthetic enzymes. Quantitative real-time PCR and the Seahorse assay were used to determine the effect of norepinephrine on gastric cancer cell glycolysis. MAOA expression in cancer tissues was analyzed by immunohistochemistry and was compared with the patient SUVmax value of PET-CT and other clinicopathological characteristics. Results The norepinephrine levels were markedly high in gastric cancer tissue, while the norepinephrine-degrading enzymes MAOA and MAOB showed low expression. High norepinephrine levels were associated with activated glycolysis. The MAOA or MAOB expression levels in tumor tissue were closely correlated with the patient SUV max values of PET-CT and immunotherapy evaluation indices, such as PD-L1 and the microsatellite status. Conclusions Norepinephrine shows relatively higher expression in gastric cancer tissue than in normal tissue, and its expression level is associated with the glycolysis levels in patients. The norepinephrine-degrading enzymes MAOA and MAOB have significant expression differences in cancer and normal tissue, and their missing or low expression may predict immune therapy outcomes for gastric cancer patients. High norepinephrine levels with metabolic abnormalities may be more suitable for metabolic targeted therapy or immunotherapy.

A High Level of Noradrenaline in Serum is Related to Depressive Symptoms in Early Pregnancy

Prenatal depression is a common disease, and it is an important risk factor for depression of postpartum and the diseases of newborn. However, this diagnosis of disease was deeply dependent on questionnaires evaluation by psychologists. The methods of evaluating and monitoring depression in the clinical laboratory are very limited. We dynamically determined serum cytokines (GM-CSF, Il-1[Formula: see text], Il-2, Il-3, Il-4, Il-5, Il-6, Il-10, Il-12, Il-17, TNF-[Formula: see text] and IFN-[Formula: see text]) and catecholamine (CA) hormone (adrenaline (AD) noradrenaline (NA) and dopamine (DA)) to screen valuable markers evaluating depression in pregnancy. A higher rate of anxiety in pregnant women was 73.58% (78/106) during early pregnancy, compared with it in middle pregnancy. A higher rate of depression in pregnant women was 31.73% (33/104) compared with it during early pregnancy. During early pregnancy, there were no significant differences in cytokine, AD and DA between healthy pregnant women, anxious and depressed pregnant women. But the severely depressed pregnant women had a high level of NA ([Formula: see text][Formula: see text]pg/mL versus [Formula: see text][Formula: see text]pg/mL, [Formula: see text]) during early pregnancy. The depressed pregnant women with vaginal bleeding were at a high-level NA. During middle pregnancy, IL-1[Formula: see text] ([Formula: see text]), IL-6 ([Formula: see text]) and IL-10 levels ([Formula: see text]) were significantly higher in depressed women than in healthy women. There was no significant difference in CA hormones between healthy women and depressed women. Our study showed that levels of cytokines and CA hormones kept shifting during the pregnancy process. A continuous high level of NA in serum might be related to depression during early pregnancy and might have a possibility of inducing vaginal bleeding.