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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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Effect of Sacubitril/Valsartan on circulating catecholamine levels during a 6-month follow-up in heart failure patients. Timeo Danaos et dona ferentes?
Chalikias, G, Kikas, P, Thomaidis, A, Rigopoulos, P, Pistola, A, Lantzouraki, A, Zisimopoulos, A, Tziakas, D
Acta cardiologica. 2021;(4):396-401
Abstract
We assessed the effect of Sacubitril/Valsartan on circulating catecholamine levels in patients with HF in an observational cohort study. We included 108 consecutive HF patients attending our HF Outpatients Clinic who were eligible to Sacubitril/Valsartan according to the PARADIGM-HF inclusion and exclusion criteria. We furthermore included 58 stable HF patients under optimal medical therapy as a control group. Norepinephrine and epinephrine were measured with immunoradiometric assays at baseline, at 3- and at 6-month time follow-up. Compared to baseline levels there was no change at three months in epinephrine (p = 0.177) or norepinephrine (p = 0.815) concentrations. At 6 months norepinephrine remained unchanged (p = 0.359). However, at 6 months we observed a significant increase in epinephrine levels compared to baseline [66 pg/mL (37-93) vs 38 pg/mL (18-74), p < 0.001]. In the control group no change was observed in epinephrine levels compared to baseline (p = 0.838). This study is the first to report on the effect of the new drug Sacubitril/Valsartan on circulating catecholamine levels in HF patients. Our data show a significant increase in epinephrine levels during a 6 month follow up in stable HF patients.
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3.
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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4.
Low back pain in athletes can be controlled with acupuncture by a catecholaminergic pathway: clinical trial.
Arriaga-Pizano, L, Gómez-Jiménez, DC, Flores-Mejía, LA, Pérez-Cervera, Y, Solórzano-Mata, CJ, López-Macías, C, Isibasi, A, Torres-Rosas, R
Acupuncture in medicine : journal of the British Medical Acupuncture Society. 2020;(6):388-395
Abstract
BACKGROUND Activation of the sympathetic nervous system attenuates inflammation via catecholamines. Recent evidence has shown that electroacupuncture (EA) activates neuronal networks involved in the release of dopamine and norepinephrine that control systemic inflammation. In muscle, catecholamines are related to cyclic adenosine monophosphate (cAMP). This signaling molecule has been implicated in recovery from sustained contractile activity, which may induce muscular pain, such as that which occurs during low back pain (LBP). OBJECTIVE Our aim was to evaluate the effects of EA used for the control of LBP on the activation of the sympathetic nervous system in a randomized controlled clinical trial in athletes. METHODS Two groups of athletes with acute or chronic low back pain were studied. EA, sham EA and pharmacological treatment (diclofenac sodium) were evaluated. The outcome measures included a pain score represented by a visual analogue scale (VAS) and serum levels of catecholamines quantified by enzyme-linked immunosorbent assay. In addition, blood was collected into chilled heparin tubes, placed in 96-well cell culture plates and incubated with an equal volume of Roswell Park Memorial Institute (RPMI) medium, with lipopolysaccharide (LPS) alone or with catecholamines. Tumor necrosis factor (TNF)-α levels in the supernatants were analyzed. RESULTS The results indicated that the initial pain ratings did not differ between the groups analyzed. EA induced epinephrine secretion but not norepinephrine or dopamine secretion. Although EA and pharmacological treatment did not differ in terms of pain relief, in vitro epinephrine and norepinephrine reduced TNF-α production in response to LPS stimuli. CONCLUSION EA activates the sympathetic nervous system and induces the release of epinephrine, which could ameliorate inflammation and protect muscular tissue in addition to relieving pain.
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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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Structural studies on inhibitory mechanisms of antibiotic, corticosteroid and catecholamine molecules on lactoperoxidase.
Sheikh, IA, Jiffri, EH, Ashraf, GM, Kamal, MA, Beg, MA
Life sciences. 2018;:412-419
Abstract
AIM: Lactoperoxidase (LPO) is an essential protein with broad spectrum antimicrobial activity present in mammalian milk. It imparts immunity to infants against wide range of pathogenic infections. Several in vitro studies have shown inhibition of LPO activity by pharmaceutical compounds including commonly used antibiotics such as ampicillin and gentamicin, and molecules like prednisolone, norepinephrine, etc. Prescription of such drugs to lactating mothers might have adverse health effects on infants. The aim of our study was the elucidation of the structural aspects of the inhibitory mechanism of ampicillin, gentamicin, amoxicillin, prednisolone and norepinephrine on LPO. MATERIAL AND METHODS Three dimensional structure of camel LPO (cLPO) was developed using homology modeling and used for in silico experimental studies. The Schrödinger induced fit docking along with binding affinity estimation experiments were performed. The cLPO and Ligands were prepared using Protein Preparation Wizard and Ligprep modules available in Schrodinger suite. For estimating Binding affinity Prime Molecular Mechanics with Generalized Born and Surface Area (MMGB-SA) module was used. KEY RESULTS The five drug ligands formed three to five hydrogen bonding interactions with cLPO. Amino acids Arg-231, Asp-232, Ser-370, Arg-371 and Glu-374 of cLPO were crucial for these interactions. The binding affinity values for gentamicin were highest and for norepinephrine were the lowest. SIGNIFICANCE This study concludes that the five drug molecules show potential ability to inhibit the LPO activity. Further, a very high sequence similarity of cLPO with human LPO imparts high significance to these conclusions in relation to human health especially in new born infants.
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THE PHYSIOLOGY BEHIND DIABETES MELLITUS IN PATIENTS WITH PHEOCHROMOCYTOMA: A REVIEW OF THE LITERATURE.
Mesmar, B, Poola-Kella, S, Malek, R
Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists. 2017;(8):999-1005
Abstract
OBJECTIVE This paper reviews the physiologic mechanisms responsible for glucose intolerance and diabetes mellitus in patients with pheochromocytoma. METHODS Google Scholar and PubMed were searched using the following key words: "diabetes," "pheochromocytoma," "adrenoreceptors," and "hyperglycemia." All the articles that were retrieved and reviewed were in the English language. RESULTS Glucose intolerance and diabetes mellitus, resulting from high circulating levels of catecholamines, are mainly the product of compromised insulin secretion from the β-cells in the pancreas, decreased glucose uptake in the peripheral tissues, and increased insulin resistance. CONCLUSION As pheochromocytomas mainly present with cardiovascular and autonomic hyperfunctioning, it is important to understand the metabolic disorders associated with this rare disease. Hyperglycemia is an associated metabolic abnormality which can drastically improve after tumor resection, and significant downscaling of anti-hyperglycemic therapy is often required. ABBREVIATIONS GLUT4 = glucose transporter type 4 HbA1c = hemoglobin A1c IL = interleukin OGTT = oral glucose tolerance test.
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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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Coronary artery disease and lunar catecholamine cardiomyopathy.
Rowe, WJ
International journal of cardiology. 2017;:42-46
Abstract
Show how lunar catecholamine cardiomyopathy alone, exemplified by Neil Armstrong's single space walk, prior to exposure to inhalation of fine particulate matter, can trigger " Neil Armstrong Syndrome" or by Irwin with coronary, possibly hypertensive heart disease, and catecholamine cardiomyopathy. With space flight, invariably magnesium ion deficits, catecholamine elevations, vicious cycles. Design Use lunar heart rates while configuring rover to show severe tachycardia component of the syndrome. Use Irwin's stress test-" cyanotic fingernails" to support Apollo 15 Space Syndrome. Use Irwin's autobiography to compensate for often incomplete data. Results Paper shows that both Irwin as well as Armstrong meet criteria of my 2nd. Space Syndrome: severe thirst, severe shortness of breath, severe tachycardia, the latter, corrected by replenishing plasma volume. Conclusions Irwin, with a history of hypertension prior to the Apollo 15 mission and classical angina during Earth reentry, may have had coronary as well as hypertensive heart disease whereas there was no evidence that Armstrong had these conditions prior or during his mission. However both, on return to Earth, had abnormal stress tests.
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Hormonal and Metabolic Responses to a Single Bout of Resistance Exercise in Prader-Willi Syndrome
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Rubin, DA, Clark, SJ, Haqq, AM, Castner, DM, Ng, J, Judelson, DA
Hormone research in paediatrics. 2017;(3):153-161
Abstract
BACKGROUND Prader-Willi syndrome (PWS) is characterized by excessive adiposity. Excess adiposity negatively affects hormonal and metabolic responses to aerobic exercise. This study determined whether PWS and/or adiposity affected hormonal and metabolic responses to resistance exercise. METHODS Eleven children with PWS (11.4 ± 3.1 years, 43.9 ± 7.5% body fat), 12 lean children (9.3 ± 1.4 years, 18.3 ± 4.9% body fat), and 13 obese children (9.6 ± 1.3 years, 40.3 ± 5.2% body fat) participated. The children stepped onto an elevated platform while wearing a weighted vest for 6 sets of 10 repetitions per leg (sets separated by 1 min of rest). For the children with PWS, the platform height was 23.0 cm and vest load was computed as (20% of stature × 50% of lean body mass)/23.0 cm. For the controls, the platform height was 20% of the stature and vest load 50% of the lean body mass. Blood samples were obtained before, immediately after, and during recovery from exercise (+15, +30, and +60 min). RESULTS All groups had similar catecholamine, insulin, and glucagon responses. The groups showed no major differences in glucose and lactate levels. The PWS children demonstrated earlier increases in fatty acids during recovery and higher glycerol and ketone levels than the controls. CONCLUSION The PWS children demonstrated largely intact hormonal, glycolytic, and lipolytic responses to lower-body resistance exercise. In PWS, elevated ketone levels suggest an incomplete fat oxidation.
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