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1.
Flight hormones as therapeutic target for novel Coronavirus infectious disease.
Ouyang, SH, Su, H, He, JP, Li, XX, Lu, DM
European review for medical and pharmacological sciences. 2021;(5):2415-2417
Abstract
Coronavirus Disease 2019 (COVID-19) pandemic has made more awful effect on wellbeing and economy worldwide on an extraordinary scale. Angiotensin I Converting Enzyme 2 (ACE2), the principal receptor of SARS-CoV2, has been found to be communicated with Dopa decarboxylase in unwinding the connection of catecholamines with COVID-19 infection. Cardiovascular (CV) sickness, diabetes, hypertension, and related conditions cause significant risks during the current situation and the affected people are under basic observation around the world. The hypertension and diabetes are related with alterations in the degrees of catecholamines associated with renal gland. The naive form of renal dopaminergic framework is related with the expanded reabsorption of sodium resulting in downregulation of the ACE2 expression. Catecholamine biosynthesis is managed by counter-controlling angiotensin type 1R (AT1R) and angiotensin type 2R (AT2R), incitement of AT2 lessens catecholamine biosynthesis by means of a diminishing in cGMP levels likewise incitement of AT1 initiate catecholamine biosynthesis. This audit sums up the conceivable contribution of catecholamines in intense COVID-19 contamination and furthermore featured possible restorative adequacy of catecholamine flagging pathways against the incessant SARS-CoV-2.
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No modulation of postprandial metabolism by transcutaneous auricular vagus nerve stimulation: a cross-over study in 15 healthy men.
Vosseler, A, Zhao, D, Fritsche, L, Lehmann, R, Kantartzis, K, Small, DM, Peter, A, Häring, HU, Birkenfeld, AL, Fritsche, A, et al
Scientific reports. 2020;(1):20466
Abstract
Experimental evidence suggests a crucial role of the autonomic nervous system in whole body metabolism with major regulatory effects of the parasympathetic branch in postprandial adaptation. However, the relative contribution of this mechanism is still not fully clear in humans. We therefore compared the effects of transcutaneous auricular vagus nerve stimulation (taVNS, Cerbomed Nemos) with sham stimulation during an oral glucose tolerance test in a randomized, single-blind, cross-over design in 15 healthy lean men. Stimulation was performed for 150 min, 30 min before and during the entire oral glucose tolerance test with stimulation cycles of 30 s of on-phase and 30 s of off-phase and a 25 Hz impulse. Heart rate variability and plasma catecholamine levels were assessed as proxies of autonomic tone in the periphery. Neither analyzed heart rate variability parameters nor plasma catecholamine levels were significantly different between the two conditions. Plasma glucose, insulin sensitivity and insulin secretion were also comparable between conditions. Thus, the applied taVNS device or protocol was unable to achieve significant effects on autonomic innervation in peripheral organs. Accordingly, glucose metabolism remained unaltered. Therefore, alternative approaches are necessary to investigate the importance of the autonomic nervous system in postprandial human metabolism.
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Pheochromocytoma and paraganglioma: clinical feature-based disease probability in relation to catecholamine biochemistry and reason for disease suspicion.
Geroula, A, Deutschbein, T, Langton, K, Masjkur, J, Pamporaki, C, Peitzsch, M, Fliedner, S, Timmers, HJLM, Bornstein, SR, Beuschlein, F, et al
European journal of endocrinology. 2019;(4):409-420
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Abstract
OBJECTIVE Hypertension and symptoms of catecholamine excess are features of pheochromocytomas and paragangliomas (PPGLs). This prospective observational cohort study assessed whether differences in presenting features in patients tested for PPGLs might assist establishing likelihood of disease. DESIGN AND METHODS Patients were tested for PPGLs because of signs and symptoms, an incidental mass on imaging or routine surveillance due to previous history or hereditary risk. Patients with (n = 245) compared to without (n = 1820) PPGLs were identified on follow-up. Differences in presenting features were then examined to assess the probability of disease and relationships to catecholamine excess. RESULTS Hyperhidrosis, palpitations, pallor, tremor and nausea were 30-90% more prevalent (P < 0.001) among patients with than without PPGLs, whereas headache, flushing and other symptoms showed little or no differences. Although heart rates were higher (P < 0.0001) in patients with than without PPGLs, blood pressures were not higher and were positively correlated to BMI, which was lower (P < 0.0001) in patients with than without PPGLs. From these differences in clinical features, a score system was established that indicated a 5.8-fold higher probability of PPGLs in patients with high than low scores. Higher scores among patients with PPGLs were associated, independently of tumor size, with higher biochemical indices of catecholamine excess. CONCLUSIONS This study identifies a complex of five signs and symptoms combined with lower BMI and elevated heart rate as key features in patients with PPGLs. Prevalences of these features, which reflect variable tumoral catecholamine production, may be used to triage patients according to likelihood of disease.
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Catecholamine-Dependent β-Adrenergic Signaling in a Pluripotent Stem Cell Model of Takotsubo Cardiomyopathy.
Borchert, T, Hübscher, D, Guessoum, CI, Lam, TD, Ghadri, JR, Schellinger, IN, Tiburcy, M, Liaw, NY, Li, Y, Haas, J, et al
Journal of the American College of Cardiology. 2017;(8):975-991
Abstract
BACKGROUND Takotsubo syndrome (TTS) is characterized by an acute left ventricular dysfunction and is associated with life-threating complications in the acute phase. The underlying disease mechanism in TTS is still unknown. A genetic basis has been suggested to be involved in the pathogenesis. OBJECTIVES The aims of the study were to establish an in vitro induced pluripotent stem cell (iPSC) model of TTS, to test the hypothesis of altered β-adrenergic signaling in TTS iPSC-cardiomyocytes (CMs), and to explore whether genetic susceptibility underlies the pathophysiology of TTS. METHODS Somatic cells of patients with TTS and control subjects were reprogrammed to iPSCs and differentiated into CMs. Three-month-old CMs were subjected to catecholamine stimulation to simulate neurohumoral overstimulation. We investigated β-adrenergic signaling and TTS cardiomyocyte function. RESULTS Enhanced β-adrenergic signaling in TTS-iPSC-CMs under catecholamine-induced stress increased expression of the cardiac stress marker NR4A1; cyclic adenosine monophosphate levels; and cyclic adenosine monophosphate-dependent protein kinase A-mediated hyperphosphorylation of RYR2-S2808, PLN-S16, TNI-S23/24, and Cav1.2-S1928, and leads to a reduced calcium time to transient 50% decay. These cellular catecholamine-dependent responses were mainly mediated by β1-adrenoceptor signaling in TTS. Engineered heart muscles from TTS-iPSC-CMs showed an impaired force of contraction and a higher sensitivity to isoprenaline-stimulated inotropy compared with control subjects. In addition, altered electrical activity and increased lipid accumulation were detected in catecholamine-treated TTS-iPSC-CMs, and were confirmed by differentially expressed lipid transporters CD36 and CPT1C. Furthermore, we uncovered genetic variants in different key regulators of cardiac function. CONCLUSIONS Enhanced β-adrenergic signaling and higher sensitivity to catecholamine-induced toxicity were identified as mechanisms associated with the TTS phenotype. (International Takotsubo Registry [InterTAK Registry] [InterTAK]; NCT01947621).
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Blood Pressure Profile and Hypertensive Organ Damage in COPD Patients and Matched Controls. The RETAPOC Study.
Golpe, R, Mateos-Colino, A, Testa-Fernández, A, Pena-Seijo, M, Rodríguez-Enríquez, M, González-Juanatey, C, Martín-Vázquez, FJ, Pose-Reino, A, Domínguez-Pin, N, Garnacho-Gayarre, N, et al
PloS one. 2016;(6):e0157932
Abstract
BACKGROUND Several studies suggest that there is a pathogenic link between chronic obstructive pulmonary disease (COPD) and cardiovascular diseases. On the other hand, increased sympathetic tone has been described in several respiratory diseases. Our objective was to determine whether hypertension mediated by sympathetic overactivity is a mechanism that explains the association between COPD and cardiovascular diseases. METHODS Prospective nested case-control observational study; 67 COPD patients were matched 1:1 by sex and age to controls with smoking history. 24 hour-blood pressure monitoring, urinary catecholamines and their metabolites measurement, echocardiography, carotid ultrasound examination, nocturnal oximetry and retinography were performed. FINDINGS classic cardiovascular risk factors and comorbidities were similarly distributed between cases and controls. No significant differences for blood pressure variables (difference for mean systolic blood pressure: -0·13 mmHg; 95% CI: -4·48,4·20; p = 0·94; similar results for all blood presssure variables) or catecholamines values were found between both groups. There was a tendency for lower left ventricle ejection fraction in the COPD cases, that approached statistical significance (64·8 ± 7·4 vs 67·1 ± 6·2, p = 0·05). There were no differences in the retinal arteriovenous ratio, the carotid intima-media thickness, or the number of carotid plaques, between cases and controls. Fibrinogen values were higher in the COPD group (378·4 ± 69·6 vs 352·2 ± 45·6 mg/dL, p = 0·01) and mean nocturnal oxygen saturation values were lower for COPD patients (89·0 ± 4·07 vs 92·3 ± 2·2%, p < 0·0001). INTERPRETATION Hypertension induced by sympathetic overactivity does not seem to be a mechanism that could explain the association between COPD and cardiovascular disease.
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Impact of early enteral versus parenteral nutrition on mortality in patients requiring mechanical ventilation and catecholamines: study protocol for a randomized controlled trial (NUTRIREA-2).
Brisard, L, Le Gouge, A, Lascarrou, JB, Dupont, H, Asfar, P, Sirodot, M, Piton, G, Bui, HN, Gontier, O, Hssain, AA, et al
Trials. 2014;:507
Abstract
BACKGROUND Nutritional support is crucial to the management of patients receiving invasive mechanical ventilation (IMV) and the most commonly prescribed treatment in intensive care units (ICUs). International guidelines consistently indicate that enteral nutrition (EN) should be preferred over parenteral nutrition (PN) whenever possible and started as early as possible. However, no adequately designed study has evaluated whether a specific nutritional modality is associated with decreased mortality. The primary goal of this trial is to assess the hypothesis that early first-line EN, as compared to early first-line PN, decreases day 28 all-cause mortality in patients receiving IMV and vasoactive drugs for shock. METHODS/DESIGN The NUTRIREA-2 study is a multicenter, open-label, parallel-group, randomized controlled trial comparing early PN versus early EN in critically ill patients requiring IMV for an expected duration of at least 48 hours, combined with vasoactive drugs, for shock. Patients will be allocated at random to first-line PN for at least 72 hours or to first-line EN. In both groups, nutritional support will be started within 24 hours after IMV initiation. Calorie targets will be 20 to 25 kcal/kg/day during the first week, then 25 to 30 kcal/kg/day thereafter. Patients receiving PN may be switched to EN after at least 72 hours in the event of shock resolution (no vasoactive drugs for 24 consecutive hours and arterial lactic acid level below 2 mmol/L). On day 7, all patients receiving PN and having no contraindications to EN will be switched to EN. In both groups, supplemental PN may be added to EN after day 7 in patients with persistent intolerance to EN and inadequate calorie intake. We plan to recruit 2,854 patients at 44 participating ICUs. DISCUSSION The NUTRIREA-2 study is the first large randomized controlled trial designed to assess the hypothesis that early EN improves survival compared to early PN in ICU patients. Enrollment started on 22 March 2013 and is expected to end in November 2015. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01802099 (registered 27 February 2013).
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Clinical features and pharmacotherapy of childhood monoamine neurotransmitter disorders.
Ng, J, Heales, SJ, Kurian, MA
Paediatric drugs. 2014;(4):275-91
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Abstract
Childhood neurotransmitter disorders are increasingly recognised as an expanding group of inherited neurometabolic syndromes. They are caused by disturbance in synthesis, metabolism, and homeostasis of the monoamine neurotransmitters, including the catecholamines (dopamine, norepinephrine, and epinephrine) and serotonin. Disturbances in monoamine neurotransmission will lead to neurological symptoms that often overlap with clinical features of other childhood neurological disorders (such as hypoxic ischaemic encephalopathy, cerebral palsy, other movement disorders, and paroxysmal conditions); consequently, neurotransmitter disorders are frequently misdiagnosed. The diagnosis of neurotransmitter disorders is made through detailed clinical assessment, analysis of cerebrospinal fluid neurotransmitters, and further supportive diagnostic investigations. Early and accurate diagnosis of neurotransmitter disorders is important, as many are amenable to therapeutic intervention. The principles of treatment for monoamine neurotransmitter disorders are mainly directly derived from understanding these metabolic pathways. In disorders characterized by enzyme deficiency, we aim to increase monoamine substrate availability, boost enzyme co-factor levels, reduce monoamine breakdown, and replace depleted levels of monoamines with pharmacological analogs as clinically indicated. Most monoamine neurotransmitter disorders lead to reduced levels of central dopamine and/or serotonin. Complete amelioration of motor symptoms is achievable in some disorders, such as Segawa's syndrome, and, in other conditions, significant improvement in quality of life can be attained with pharmacotherapy. In this review, we provide an overview of the clinical features and current treatment strategies for childhood monoamine neurotransmitter disorders.
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Arrhythmias, elicited by catecholamines and serotonin, vanish in human chronic atrial fibrillation.
Christ, T, Rozmaritsa, N, Engel, A, Berk, E, Knaut, M, Metzner, K, Canteras, M, Ravens, U, Kaumann, A
Proceedings of the National Academy of Sciences of the United States of America. 2014;(30):11193-8
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Atrial fibrillation (AF) is the most common heart rhythm disorder. Transient postoperative AF can be elicited by high sympathetic nervous system activity. Catecholamines and serotonin cause arrhythmias in atrial trabeculae from patients with sinus rhythm (SR), but whether these arrhythmias occur in patients with chronic AF is unknown. We compared the incidence of arrhythmic contractions caused by norepinephrine, epinephrine, serotonin, and forskolin in atrial trabeculae from patients with SR and patients with AF. In the patients with AF, arrhythmias were markedly reduced for the agonists and abolished for forskolin, whereas maximum inotropic responses were markedly blunted only for serotonin. Serotonin and forskolin produced spontaneous diastolic Ca(2+) releases in atrial myocytes from the patients with SR that were abolished or reduced in myocytes from the patients with AF. For matching L-type Ca(2+)-current (ICa,L) responses, serotonin required and produced ∼ 100-fold less cAMP/PKA at the Ca(2+) channel domain compared with the catecholamines and forskolin. Norepinephrine-evoked ICa,L responses were decreased by inhibition of Ca(2+)/calmodulin-dependent kinase II (CaMKII) in myocytes from patients with SR, but not in those from patients with AF. Agonist-evoked phosphorylation by CaMKII at phospholamban (Thr-17), but not of ryanodine2 (Ser-2814), was reduced in trabeculae from patients with AF. The decreased CaMKII activity may contribute to the blunting of agonist-evoked arrhythmias in the atrial myocardium of patients with AF.
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Pheochromocytoma and markers of oxidative stress.
Turková, H, Petrák, O, Skrha, J, Widimský, J, Zelinka, T
Physiological research. 2013;(3):331-5
Abstract
High levels of catecholamines in pheochromocytoma (PHEO) are associated with risk of cardiovascular complications. In this study, we looked for potential differences in markers of oxidative stress - vitamin C, superoxide dismutase (SOD) and malondialdehyde (MDA) in PHEO before and after the operation. We studied 18 subjects with PHEO who were examined before and approximately one year after the successful tumor removal (free of disease). All subjects had elevated urinary epinephrine and/or norepinephrine levels before the operation. Vitamin C levels increased significantly after the operation from 61+/-27 to 77+/-20 micromol/l (P=0.02), and MDA decreased significantly after the tumor removal from 2.6+/-0.4 to 2.0+/-0.6 micromol/l (P=0.01). However, no changes were found in SOD activity before and after the operation. In conclusion, increased catecholamine production in PHEO is accompanied by decreased levels of vitamin C and increased levels of MDA which may indicate the activation of oxidative stress in PHEO. Successful operation was associated with lowering of oxidative stress by using both biomarkers. On the contrary, no changes in SOD activity before and after the tumor removal were noted.
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Involvement of catecholaminergic medullary pathways in cardiovascular responses to acute changes in circulating volume.
Cravo, SL, Lopes, OU, Pedrino, GR
Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas. 2011;(9):877-82
Abstract
Water deprivation and hypernatremia are major challenges for water and sodium homeostasis. Cellular integrity requires maintenance of water and sodium concentration within narrow limits. This regulation is obtained through engagement of multiple mechanisms and neural pathways that regulate the volume and composition of the extracellular fluid. The purpose of this short review is to summarize the literature on central neural mechanisms underlying cardiovascular, hormonal and autonomic responses to circulating volume changes, and some of the findings obtained in the last 12 years by our laboratory. We review data on neural pathways that start with afferents in the carotid body that project to medullary relays in the nucleus tractus solitarii and caudal ventrolateral medulla, which in turn project to the median preoptic nucleus in the forebrain. We also review data suggesting that noradrenergic A1 cells in the caudal ventrolateral medulla represent an essential link in neural pathways controlling extracellular fluid volume and renal sodium excretion. Finally, recent data from our laboratory suggest that these structures may also be involved in the beneficial effects of intravenous infusion of hypertonic saline on recovery from hemorrhagic shock.