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1.
Cell Tissue Res ; 387(2): 261-274, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34816282

RESUMO

Circadian rhythms are those variations in behavioral and molecular processes of organisms that follow roughly 24 h cycles in the absence of any external cue. The hypothalamic suprachiasmatic nucleus (SCN) harbors the principal brain pacemaker driving circadian rhythms. The epithalamic habenula (Hb) contains a self-sustained circadian clock functionally coupled to the SCN. Anatomically, the Hb projects to the midbrain dopamine (DA) and serotonin (5-HT) systems, and it receives inputs from the forebrain, midbrain, and brainstem. The SCN is set by internal signals such as 5-HT or melatonin from the raphe nuclei and pineal gland, respectively. However, how the Hb clock is set by internal cues is not well characterized. Hence, in the present study, we determined whether DA, noradrenaline (NA), 5-HT, and the neuropeptides orexin (ORX) and vasopressin influence the Hb circadian clock. Using PER2::Luciferase transgenic mice, we found that the amplitude of the PER2 protein circadian oscillations from Hb explants was strongly affected by DA and NA. Importantly, these effects were dose-and region (rostral vs. caudal) dependent for NA, with a main effect in the caudal part of the Hb. Furthermore, ORX also induced a significant change in the amplitude of PER2 protein oscillations in the caudal Hb. In conclusion, catecholaminergic (DA, NA) and ORXergic transmission impacts the clock properties of the Hb clock likely contributing to the circadian regulation of motivated behaviors. Accordingly, pathological conditions that lead in alterations of catecholamine or ORX activity (drug intake, compulsive feeding) might affect the Hb clock and conduct to circadian disturbances.


Assuntos
Relógios Circadianos , Habenula , Animais , Catecolaminas/metabolismo , Ritmo Circadiano , Habenula/metabolismo , Camundongos , Camundongos Transgênicos , Proteínas Circadianas Period/genética , Proteínas Circadianas Period/metabolismo , Núcleo Supraquiasmático/metabolismo
2.
Med Sci Monit ; 28: e936114, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35422455

RESUMO

BACKGROUND Pancreatoduodenectomy is an extensive procedure with a very high risk of complications. Appropriate intraoperative fluid therapy is a subject of ongoing debate. The aim of this retrospective study was to analyze the relationship between selected preoperative parameters, intraoperative fluid therapy, and catecholamines administration during pancreatoduodenectomy. MATERIAL AND METHODS From 2011 through 2017, among pancreatoduodenectomies performed at a single university hospital, 192 patients met the inclusion criteria of the study: 105 (54.7%) males and 87 (45.3%) females with a mean age of 60.06 (±11.63) years. Correlations were assessed between sex, age, body mass index (BMI), selected comorbidities, surgery duration, American Society of Anesthesiologists (ASA) Physical Status (PS) scale, preoperative endoscopic retrograde cholangiopancreatography (ERCP) and intraoperative catecholamine administration, intraoperative fluid supply, red blood cell (RBC) concentrate and fresh frozen plasma (FFP) supply, blood loss, and diuresis. RESULTS A need for catecholamines has been shown to be more frequent in smokers (P=0.01), patients with cardiovascular comorbidities (P=0.037), high ASA PS scores (P=0.003), and preoperative ERCP (P=0.011). The need for intraoperative transfusion of RBC concentrate was more frequent in smokers (P=0.005). Surgical time was significantly longer in males (P=0.014). Among females, liberal intraoperative fluid therapy (>7.9 ml/kg/h) was more frequent in patients with thyroid comorbidities (P=0.003). CONCLUSIONS The findings of this retrospective study demonstrate the influence of comorbidities, ASA PS class, and catecholamine use on fluid therapy during pancreatoduodenectomy.


Assuntos
Transfusão de Sangue , Pancreaticoduodenectomia , Catecolaminas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Retrospectivos
3.
Blood Press ; 31(1): 71-79, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35465794

RESUMO

BACKGROUND: The Covid-19 pandemic necessitated a decrease in non-Covid-19 related diagnostic and therapeutic procedures in many countries. We explored the impact on tertiary hypertension care. METHODS: We conducted an electronic survey regarding 6 key procedures in hypertension care within the Excellence Center network of the European Society of Hypertension. RESULTS: Overall, 54 Excellence Centers from 18 European and 3 non-European countries participated. From 2019 to 2020, there were significant decreases in the median number per centre of ambulatory blood pressure monitorings (ABPM: 544/289 for 2019/2020), duplex ultrasound of renal arteries (Duplex RA: 88.5/55), computed tomographic/magnetic resonance imaging angiography of renal arteries (CT/MRI RA: 66/19.5), percutaneous angioplasties of renal arteries (PTA RA: 5/1), laboratory tests for catecholamines (116/67.5) and for renin/aldosterone (146/83.5) (p < 0.001 for all comparisons, respectively). While reductions in all assessed diagnostic and therapeutic procedures were observed in all annual 3-months periods in the comparisons between 2019 and 2020, the most pronounced reduction occurred between April and June 2020, which was the period of the first wave and the first lockdown in most affected countries. In this period, the median reductions in 2020, as compared to 2019, were 50.7% (ABPM), 47.1% (Duplex RA), 50% (CT/MRI RA), 57.1% (PTA RA), 46.9% (catecholamines) and 41.0% (renin/aldosterone), respectively. Overall differences in reduction between 3-month time intervals were statistically highly significant. CONCLUSION: Diagnostic and therapeutic procedures related to hypertension were dramatically reduced during the first year of the Covid-19 pandemic, with the largest reduction during the first lockdown. The long-term consequences regarding blood pressure control and, ultimately, cardiovascular events remain to be investigated.


Assuntos
COVID-19 , Hipertensão , Aldosterona , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial/métodos , COVID-19/epidemiologia , Catecolaminas , Controle de Doenças Transmissíveis , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Pandemias , Renina
4.
Toxins (Basel) ; 14(4)2022 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-35448863

RESUMO

Gambierol inhibits voltage-gated K+ (KV) channels in various excitable and non-excitable cells. The purpose of this work was to study the effects of gambierol on single rat fetal (F19-F20) adrenomedullary cultured chromaffin cells. These excitable cells have different types of KV channels and release catecholamines. Perforated whole-cell voltage-clamp recordings revealed that gambierol (100 nM) blocked only a fraction of the total outward K+ current and slowed the kinetics of K+ current activation. The use of selective channel blockers disclosed that gambierol did not affect calcium-activated K+ (KCa) and ATP-sensitive K+ (KATP) channels. The gambierol concentration necessary to inhibit 50% of the K+ current-component sensitive to the polyether (IC50) was 5.8 nM. Simultaneous whole-cell current-clamp and single-cell amperometry recordings revealed that gambierol did not modify the membrane potential following 11s depolarizing current-steps, in both quiescent and active cells displaying repetitive firing of action potentials, and it did not increase the number of exocytotic catecholamine release events, with respect to controls. The subsequent addition of apamin and iberiotoxin, which selectively block the KCa channels, both depolarized the membrane and enhanced by 2.7 and 3.5-fold the exocytotic event frequency in quiescent and active cells, respectively. These results highlight the important modulatory role played by KCa channels in the control of exocytosis from fetal (F19-F20) adrenomedullary chromaffin cells.


Assuntos
Células Cromafins , Ciguatoxinas , Trifosfato de Adenosina/farmacologia , Animais , Cálcio/farmacologia , Catecolaminas/farmacologia , Células Cultivadas , Ciguatoxinas/farmacologia , Potássio , Ratos
5.
J Assoc Physicians India ; 70(4): 11-12, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35443409

RESUMO

ICH is one of the most serious neurological emergency which can result in high mortality which may be related to catecholamine release. We aim to evaluate serum catecholamine levels in acute ICH and correlate their levels with clinical parameters of stress and outcome. MATERIAL: Consecutive patients with CT proven ICH within 7 days of ictus were included and their clinical finding, SIRS Parameters, GCS, NIH score, laboratory parameters (ESR, CRP) were evaluated. Serum Catecholamine (DA, NE, E) levels were measured by LCMS. The patients were followed up at discharge and one month, the outcome was defined by mortality and 1 month modified Rankin scale (good 0-2, poor >2). OBSERVATION: There were 31 patients of acute ICH. Patients were admitted 1 to 2 days after ictus. Among the patients 19 were male and 12 were female.Their age ranged from 31 to 86 with mean 53.3+- 16.7. History of hypertension was present in 27.3% of patients. Their average GCS was median 12 (6.0, 15.0) and NIHSS was 12.5 (8.5, 22) Their average ESR was 30 (13,56) and average CRP was 1.8 (1.1, 5.9). Almost all pateints had raised SIRS parameters. There was an increase in levels of Dopamine (63.2 pg/ml), Epinephrine (73.5 pg/ml) and Norepinephrine (390pg/ml) on admission as compared to their levels 1 week after ictus or on discharge (Dopamine 35.6, Epinephrine 52.1, and Norepinephrine 241 pg/ml). CONCLUSION: CA surge is common in ICH pateints and it correlates with severity and outcome of patient. 6 pateints died in the hospital 72 % of patients had poor outcome. Catecholamine levels were higher in poor outcome patients.


Assuntos
Dopamina , Acidente Vascular Cerebral , Catecolaminas , Hemorragia Cerebral , Epinefrina , Feminino , Humanos , Masculino , Norepinefrina , Prognóstico , Síndrome de Resposta Inflamatória Sistêmica
6.
Transl Psychiatry ; 12(1): 151, 2022 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-35397615

RESUMO

Noradrenergic and dopaminergic neurons are involved in cognitive functions, relate to behavioral and psychological symptoms in dementia and are affected in Alzheimer's disease (AD). Amyloid plaques (A), neurofibrillary tangles (T) and neurodegeneration (N) hallmarks the AD neuropathology. Today, the AT(N) pathophysiology can be assessed through biomarkers. Previous studies report cerebrospinal fluid (CSF) catecholamine concentrations in AD patients without biomarker refinement. We explored if CSF catecholamines relate to AD clinical presentation or neuropathology as reflected by CSF biomarkers. CSF catecholamines were analyzed in AD patients at the mild cognitive impairment (MCI; n = 54) or dementia stage (n = 240) and in cognitively unimpaired (n = 113). CSF biomarkers determined AT status and indicated synaptic damage (neurogranin). The AD patients (n = 294) had higher CSF noradrenaline and adrenaline concentrations, but lower dopamine concentrations compared to the cognitively unimpaired (n = 113). AD patients in the MCI and dementia stage of the disease had similar CSF catecholamine concentrations. In the CSF neurogranin positively associated with noradrenaline and adrenaline but not with dopamine. Adjusted regression analyses including AT status, CSF neurogranin, age, gender, and APOEε4 status verified the findings. In restricted analyses comparing A+T+ patients to A-T- cognitively unimpaired, the findings for CSF adrenaline remained significant (p < 0.001) but not for CSF noradrenaline (p = 0.07) and CSF dopamine (p = 0.33). There were no differences between A+T+ and A-T- cognitively unimpaired. Thus, we find alterations in CSF catecholamines in symptomatic AD and the CSF adrenergic transmitters to increase simultaneously with synaptic damage as indexed by CSF neurogranin.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/complicações , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Catecolaminas , Disfunção Cognitiva/complicações , Dopamina , Epinefrina , Humanos , Neurogranina/líquido cefalorraquidiano , Norepinefrina , Fragmentos de Peptídeos/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidiano
7.
Mikrochim Acta ; 189(5): 180, 2022 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-35391571

RESUMO

Dopamine (DA), epinephrine (EP), and norepinephrine (NEP) are the main catecholamine of clinical interest, as they play crucial roles in the regulation of nervous and cardiovascular systems and are involved in some brain behaviors, such as stress, panic, anxiety, and depression. Therefore, there is an urgent need for a reliable sensing device able to provide their continuous monitoring in a minimally invasive manner. In this work, the first highly nanoporous gold (h-nPG) microneedle-based sensor is presented for continuous monitoring of catecholamine in interstitial fluid (ISF). The h-nPG microneedle-based gold electrode was prepared by a simple electrochemical self-templating method that involves two steps, gold electrodeposition and hydrogen bubbling at the electrode surface, realized by sweeping the potential between + 0.8 V and 0 V vs Ag/AgCl for 25 scans in a 10 mM HAuCl4 solution containing 2.5 M NH4Cl, and successively applying a fixed potential of - 2 V vs Ag/AgCl for 60 s. The resulting microneedle-based h-nPG sensor displays an interference-free total catecholamine detection expressed as NEP concentration, with a very low LOD of 100 nM, excellent sensitivity and stability, and fast response time (< 4 s). The performance of the h-nPG microneedle array sensor was successively assessed in artificial ISF and in a hydrogel skin model at typical physiological concentrations.


Assuntos
Ouro , Nanoporos , Catecolaminas , Eletrodos , Agulhas
8.
Circulation ; 145(13): 1002-1019, 2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35344411

RESUMO

Takotsubo syndrome is a condition characterized by acute transient left ventricular systolic dysfunction, which at presentation can be challenging to distinguish from acute myocardial infarction. Although previously thought to be a benign, self-limiting condition, recent studies have confirmed that patients with takotsubo syndrome have persistent subtle ongoing cardiac dysfunction, and many continue to have limiting symptoms despite restoration of left ventricular ejection fraction. Moreover, these patients have a substantial burden of morbidity and mortality, as well, with high rates of subsequent major adverse cardiovascular events that approach those of patients with acute coronary syndrome. The mechanisms behind this condition remain elusive. Despite substantial research, the medical community continues to have an incomplete understanding of its underlying pathogenesis and pathophysiology. Catecholamine-induced myocardial injury is the most established and well-known theory, but this does not explain all the clinical features and presentations of the condition, and numerous other pathways and abnormalities are emerging. Because of the poor understanding of its underlying pathophysiology, there is a lack of evidence-based interventions to treat the acute episode, to avoid recurrences, and to prevent major adverse cardiovascular events. This highlights the need for further research to gain a better understanding of the underlying pathophysiology to inform appropriate randomized controlled trials of interventions targeting the causative pathways. Only then can evidence-based management strategies be established to improve clinical outcomes of this potentially lethal condition.


Assuntos
Infarto do Miocárdio , Cardiomiopatia de Takotsubo , Catecolaminas , Humanos , Infarto do Miocárdio/diagnóstico , Volume Sistólico , Cardiomiopatia de Takotsubo/diagnóstico , Cardiomiopatia de Takotsubo/terapia , Função Ventricular Esquerda
9.
Transl Neurodegener ; 11(1): 15, 2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-35260194

RESUMO

BACKGROUND: Parkinson's disease (PD) is characterized by intra-neuronal deposition of the protein α-synuclein (α-syn) and by deficiencies of the catecholamines dopamine and norepinephrine (NE) in the brain and heart. Accumulation of α-syn in sympathetic noradrenergic nerves may provide a useful PD biomarker; however, whether α-syn buildup is pathophysiological has been unclear. If it were, one would expect associations of intra-neuronal α-syn deposition with catecholaminergic denervation and with decreased NE contents in the same samples. METHODS: We assayed immunoreactive α-syn and tyrosine hydroxylase (TH, a marker of catecholaminergic innervation) concurrently with catecholamines in coded post-mortem scalp skin, submandibular gland (SMG), and apical left ventricular myocardial tissue samples from 14 patients with autopsy-proven PD and 12 age-matched control subjects who did not have a neurodegenerative disease. RESULTS: The PD group had increased α-syn in sympathetic noradrenergically innervated arrector pili muscles (5.7 times control, P < 0.0001), SMG (35 times control, P = 0.0011), and myocardium (11 times control, P = 0.0011). Myocardial TH in the PD group was decreased by 65% compared to the control group (P = 0.0008), whereas the groups did not differ in TH in either arrector pili muscles or SMG. Similarly, myocardial NE was decreased by 92% in the PD group (P < 0.0001), but the groups did not differ in NE in either scalp skin or SMG. CONCLUSIONS: PD entails increased α-syn in skin, SMG, and myocardial tissues. In skin and SMG, augmented α-syn deposition in sympathetic nerves does not seem to be pathogenic. The pathophysiological significance of intra-neuronal α-syn deposition appears to be organ-selective and prominent in the heart.


Assuntos
Doenças Neurodegenerativas , Doença de Parkinson , alfa-Sinucleína/metabolismo , Autopsia , Biomarcadores , Catecolaminas , Humanos , Norepinefrina , Doença de Parkinson/metabolismo
10.
Neuron ; 110(9): 1450-1467, 2022 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-35316661

RESUMO

It is well established that stress has a major impact on memory, driven by the concerted action of various stress mediators on the brain. Recent years, however, have seen considerable advances in our understanding of the cellular, neural network, and cognitive mechanisms through which stress alters memory. These novel insights highlight the intricate interplay of multiple stress mediators, including-beyond corticosteroids, catecholamines, and peptides-for instance, endocannabinoids, which results in time-dependent shifts in large-scale neural networks. Such stress-induced network shifts enable highly specific memories of the stressful experience in the long run at the cost of transient impairments in mnemonic flexibility during and shortly after a stressful event. Based on these recent discoveries, we provide a new integrative framework that links the cellular, systems, and cognitive mechanisms underlying acute stress effects on memory processes and points to potential targets for treating aberrant memory in stress-related mental disorders.


Assuntos
Encéfalo , Memória , Catecolaminas , Humanos
11.
Viruses ; 14(3)2022 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-35336971

RESUMO

Previously, the association between the catecholamine biosynthetic enzyme L-Dopa decarboxylase (DDC) and Dengue virus (DV) replication was demonstrated in liver cells and was found to be mediated at least by the interaction between DDC and phosphoinositide 3-kinase (PI3K). Here, we show that biogenic amines production and uptake impede DV replication in hepatocytes and monocytes, while the virus reduces catecholamine biosynthesis, metabolism, and transport. To examine how catecholamine biosynthesis/metabolism influences DV, first, we verified the role of DDC by altering DDC expression. DDC silencing enhanced virus replication, but not translation, attenuated the negative effect of DDC substrates on the virus and reduced the infection related cell death. Then, the role of the downstream steps of the catecholamine biosynthesis/metabolism was analyzed by chemical inhibition of the respective enzymes, application of their substrates and/or their products; moreover, reserpine, the inhibitor of the vesicular monoamine transporter 2 (VMAT2), was used to examine the role of uptake/storage of catecholamines on DV. Apart from the role of each enzyme/transporter, these studies revealed that the dopamine uptake, and not the dopamine-signaling, is responsible for the negative effect on DV. Accordingly, all treatments expected to enhance the accumulation of catecholamines in the cell cytosol suppressed DV replication. This was verified by the use of chemical inducers of catecholamine biosynthesis. Last, the cellular redox alterations due to catecholamine oxidation were not related with the inhibition of DV replication. In turn, DV apart from its negative impact on DDC, inhibits tyrosine hydroxylase, dopamine beta-hydroxylase, monoamine oxidase, and VMAT2 expression.


Assuntos
Dengue , Dopamina , Catecolaminas/metabolismo , Dopamina/metabolismo , Hepatócitos/metabolismo , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Replicação Viral
12.
J Am Chem Soc ; 144(10): 4310-4314, 2022 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-35254807

RESUMO

Hofmeister effects have often been ignored in living organisms, although they affect the activity and functions of biological molecules. Herein, amperometry has been applied to show that the vesicular content, dynamics of exocytosis and vesicles opening, depend on the anionic species treatment. Compared to 100 µM Cl- treated chromaffin cells, a similar number of catecholamine molecules is released after chaotropic anions (ClO4- and SCN-) treatment, even though the vesicular catecholamine content significantly increases, suggesting a lower release fraction. In addition, there are opposite effects on the dynamics of vesicles release (shorter duration) and vesicle opening (longer duration) for chaotropic anions treated cells. Our results show anion-dependent vesicle release, vesicle opening, and vesicular content, providing understanding of the pharmacological and pathological processes induced by inorganic ions.


Assuntos
Células Cromafins , Exocitose , Ânions , Catecolaminas , Células Cromafins/fisiologia , Exocitose/fisiologia
13.
Proc Natl Acad Sci U S A ; 119(10): e2118227119, 2022 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-35238645

RESUMO

SignificanceHost-emitted stress hormones significantly influence the growth and behavior of various bacterial species; however, their cellular targets have so far remained elusive. Here, we used customized probes and quantitative proteomics to identify the target of epinephrine and the α-adrenoceptor agonist phenylephrine in live cells of the aquatic pathogen Vibrio campbellii. Consequently, we have discovered the coupling protein CheW, which is in the center of the chemotaxis signaling network, as a target of both molecules. We not only demonstrate direct ligand binding to CheW but also elucidate how this affects chemotactic control. These findings are pivotal for further research on hormone-specific effects on bacterial behavior.


Assuntos
Proteínas de Bactérias/metabolismo , Catecolaminas/fisiologia , Fatores Quimiotáticos/fisiologia , Quimiotaxia/fisiologia , Vibrio/fisiologia , Catecóis/química , Fatores Quimiotáticos/metabolismo , Ferro/análise , Sondas Moleculares/química , Ligação Proteica , Proteômica/métodos , Transdução de Sinais
14.
Int J Mol Sci ; 23(6)2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-35328583

RESUMO

Disruption to endothelial cell homeostasis results in an extensive variety of human pathologies that are particularly relevant to major trauma. Circulating catecholamines, such as adrenaline and noradrenaline, activate endothelial adrenergic receptors triggering a potent response in endothelial function. The regulation of the endothelial cell metabolism is distinct and profoundly important to endothelium homeostasis. However, a precise catalogue of the metabolic alterations caused by sustained high catecholamine levels that results in endothelial dysfunction is still underexplored. Here, we uncover a set of up to 46 metabolites that exhibit a dose-response relationship to adrenaline-noradrenaline equimolar treatment. The identified metabolites align with the glutathione-ascorbate cycle and the nitric oxide biosynthesis pathway. Certain key metabolites, such as arginine and reduced glutathione, displayed a differential response to treatment in early (4 h) compared to late (24 h) stages of sustained stimulation, indicative of homeostatic metabolic feedback loops. Furthermore, we quantified an increase in the glucose consumption and aerobic respiration in endothelial cells upon catecholamine stimulation. Our results indicate that oxidative stress and nitric oxide metabolic pathways are downstream consequences of endothelial cell stimulation with sustained high levels of catecholamines. A precise understanding of the metabolic response in endothelial cells to pathological levels of catecholamines will facilitate the identification of more efficient clinical interventions in trauma patients.


Assuntos
Catecolaminas , Óxido Nítrico , Permeabilidade Capilar , Catecolaminas/metabolismo , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Epinefrina/metabolismo , Epinefrina/farmacologia , Humanos , Óxido Nítrico/metabolismo , Norepinefrina/metabolismo , Norepinefrina/farmacologia
15.
Front Endocrinol (Lausanne) ; 13: 853878, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35355563

RESUMO

Objective: To investigate possible predictive factors of catecholamine-induced cardiomyopathy in pheochromocytoma and paraganglioma (CICMPP) patients. Methods: In all, 50 CICMPP patients and 152 pheochromocytoma and paraganglioma (PPGL) patients without CICMPP who were treated in our institution between August 2012 and April 2018 were included in this retrospective study to assess predictors of CICMPP. Results: Patients with CICMPP reported younger onset age, more clinical symptoms and signs, more family history of hypertension, and higher maximum systolic, diastolic, and mean BP and maximum HR. Medical evaluation also showed higher level of blood hematocrit, blood glucose, 24-h urine catecholamines, larger diameter of the tumor and more comorbidities, von Hippel-Lindau syndromes, and metastatic tumors in these patients. Multivariable analysis identified maximum resting HR over 115 beats/min (OR 10.05, 95% CI 3.71-27.20), maximum resting systolic BP over 180 mmHg (OR 7.17, 95% CI 2.22-23.23), blood glucose over 8.0 mmol/L (OR 6.52, 95% CI 2.25-18.86), more than 3 symptoms and signs (OR 6.05, 95% CI 1.86-19.64), and onset age under 40 years (OR 3.74, 95% CI 1.37-10.20) as independent predictors of CICMPP. Female sex (OR 5.06, 95% CI 1.19-21.54), complaint of chest pain (OR 5.84, 95% CI 1.27-26.90), and extra-adrenal tumor (OR 8.64, 95% CI 1.82-40.94) were independent predictors of Takotsubo cardiomyopathy in CICMPP. Conclusion: Maximum resting HR ≥115 beats/min, maximum resting systolic BP ≥180 mmHg, blood glucose ≥8.0 mmol/L, number of symptoms and signs ≥3, and onset age ≤40 years were found to be predictive factors for CICMPP.


Assuntos
Neoplasias das Glândulas Suprarrenais , Cardiomiopatias , Paraganglioma , Feocromocitoma , Neoplasias das Glândulas Suprarrenais/patologia , Adulto , Catecolaminas , Feminino , Humanos , Paraganglioma/complicações , Paraganglioma/patologia , Feocromocitoma/patologia , Estudos Retrospectivos
16.
J Pharm Biomed Anal ; 213: 114697, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35272126

RESUMO

Catecholamines and their metabolites act as neurotransmitters in the brain and are important for nervous system function. In the current work, a highly selective and sensitive UPLC-MS/MS assay was developed for quantitation of six catecholamines and their metabolites, including dopamine, norepinephrine, serotonin, 3,4-dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindolacetic acid from rat and mouse striatum as pharmacodynamic biomarkers to support neuroscience and pharmaceutical research. A fit-for-purpose strategy for method development, assay qualification and study support were adopted for this assay. A surrogate matrix (brain homogenizing solution absent of targeted analytes) was used for preparation of calibration samples and certain levels of quality control samples to avoid interference from endogenous baselines. Homogenized rodent striatum was derivatized by dansyl chloride to enhance the sensitivity, followed by liquid-liquid extraction with ethyl acetate in 96-well plate format. The lower limit of quantitation (LLOQ) was 0.2 ng/mL in tissue homogenate, equivalent to 3.2 pg/mg in brain tissue, which could be further reduced to ten times lower by changing the re-dissolving and injecting volume in the last sample purification step. Acceptable accuracy, precision, linearity, specificity, recovery, and matrix effect was obtained. Bench-top stability (2 h), freeze-thaw stability (3 cycles at -20 °C), and - 80 °C storage stability (up to 51 days) in both tissue homogenate and surrogate matrix along with autosampler stability (60 h at 4°C) all met acceptance criteria. This assay was successfully applied to measure the six analytes in striatum from mice treated with the neurotoxin 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), an animal model of Parkinsonism for which dosing protocols can vary widely, and further confirmed the metabolic pathway of neurotoxicity by the quantification of catecholamine metabolites. Our study is the first detailed the step-by-step recovery and pointed out the key factors for the assay to simultaneously quantify these six neurotransmitters in rodent striatum with superior sensitivity.


Assuntos
Catecolaminas , Espectrometria de Massas em Tandem , Animais , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida/métodos , Camundongos , Neurotransmissores , Ratos , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos
17.
Cells ; 11(6)2022 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-35326472

RESUMO

Over the last few years, the number of research publications about the role of catecholamines (epinephrine, norepinephrine, and dopamine) in the development of liver diseases such as liver fibrosis, fatty liver diseases, or liver cancers is constantly increasing. However, the mechanisms involved in these effects are not well understood. In this review, we first recapitulate the way the liver is in contact with catecholamines and consider liver implications in their metabolism. A focus on the expression of the adrenergic and dopaminergic receptors by the liver cells is also discussed. Involvement of catecholamines in physiological (glucose metabolism, lipids metabolism, and liver regeneration) and pathophysiological (impact on drug-metabolizing enzymes expression, liver dysfunction during sepsis, fibrosis development, or liver fatty diseases and liver cancers) processes are then discussed. This review highlights the importance of understanding the mechanisms through which catecholamines influence liver functions in order to draw benefit from the adrenergic and dopaminergic antagonists currently marketed. Indeed, as these molecules are well-known drugs, their use as therapies or adjuvant treatments in several liver diseases could be facilitated.


Assuntos
Catecolaminas , Neoplasias Hepáticas , Adrenérgicos , Humanos , Norepinefrina
18.
Endocr Relat Cancer ; 29(5): 267-272, 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35258481

RESUMO

The release of excessive amounts of catecholamine by pheochromocytoma-paragangliomas (PPGL) can lead to life-threatening catecholamine-induced cardiomyopathy (CIC). Single-nucleotide polymorphisms of the beta1 and alpha-2c adrenergic receptors alter myocyte receptor function and enhanced norepinephrine release. We tested the hypothesis that such genetic variations may impact the risk of developing CIC in the context of PPGL. Thirty-one patients with PPGL, including nine with a history of CIC, were analyzed for alpha-2-adrenergic receptors: ADRA2C, beta-1 and beta-2 adrenergic receptors: ADRB1 and ADRB2 genotyping. CIC was defined either by a history of heart failure or cardiogenic shock associated with dilated or Takotsubo cardiomyopathy. Subjects were genotyped for ADRA2C (rs61767072 for del322_325), ADRB1 (rs1801252 for Ser49Gly and rs1801253 for Arg389Gly) and ADRB2 (rs1042713 for Arg16Gly and rs1042714 for Gln27Glu). Single-locus analysis revealed that variant in ADRA2C (alpha 2CDel322-325) was more common among patients with CIC than among controls (allele frequency, 0.44 vs 0.05; P< 0.001). The lack of alpha 2CDel322-325 polymorphism has a negative predictive value of 95% for the onset of CIC. In a replication cohort including 26 patients with PPGL whom eight have developed a CIC, the association between Alpha 2CDel322-325 and CIC was confirmed (allele frequency, 0.33 vs 0.; P= 0.0001). In conclusion, Alpha 2CDel322-325 through the identification of patients at low risk of developing CIC can help physicians to better determine the most appropriate therapeutic approach, notably in patients at high risk of surgical complications.


Assuntos
Neoplasias das Glândulas Suprarrenais , Cardiomiopatias , Paraganglioma , Feocromocitoma , Receptores Adrenérgicos alfa 2 , Receptores Adrenérgicos beta 1 , Receptores Adrenérgicos beta 2 , Neoplasias das Glândulas Suprarrenais/genética , Biomarcadores , Catecolaminas , Genótipo , Humanos , Feocromocitoma/genética , Polimorfismo de Nucleotídeo Único , Receptores Adrenérgicos alfa 2/genética , Receptores Adrenérgicos beta 1/genética , Receptores Adrenérgicos beta 2/genética
19.
J Neurosci ; 42(15): 3080-3095, 2022 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-35241492

RESUMO

ClC-3, ClC-4, and ClC-5 are electrogenic chloride/proton exchangers that can be found in endosomal compartments of mammalian cells. Although the association with genetic diseases and the severe phenotype of knock-out animals illustrate their physiological importance, the cellular functions of these proteins have remained insufficiently understood. We here study the role of two Clcn3 splice variants, ClC-3b and ClC-3c, in granular exocytosis and catecholamine accumulation of adrenal chromaffin cells using a combination of high-resolution capacitance measurements, amperometry, protein expression/gene knock out/down, rescue experiments, and confocal microscopy. We demonstrate that ClC-3c resides in immature as well as in mature secretory granules, where it regulates catecholamine accumulation and contributes to the establishment of the readily releasable pool of secretory vesicles. The lysosomal splice variant ClC-3b contributes to vesicle priming only with low efficiency and leaves the vesicular catecholamine content unaltered. The related Cl-/H+ antiporter ClC-5 undergoes age-dependent downregulation in wild-type conditions. Its upregulation in Clcn3 -/- cells partially rescues the exocytotic mutant defect. Our study demonstrates how different CLC transporters with similar transport functions, but distinct localizations can contribute to vesicle functions in the regulated secretory pathway of granule secretion in chromaffin cells.SIGNIFICANCE STATEMENT Cl-/H+ exchangers are expressed along the endosomal/lysosomal system of mammalian cells; however, their exact subcellular functions have remained insufficiently understood. We used chromaffin cells, a system extensively used to understand presynaptic mechanisms of synaptic transmission, to define the role of CLC exchangers in neurosecretion. Disruption of ClC-3 impairs catecholamine accumulation and secretory vesicle priming. There are multiple ClC-3 splice variants, and only expression of one, ClC-3c, in double Cl-/H+ exchanger-deficient cells fully rescues the WT phenotype. Another splice variant, ClC-3b, is present in lysosomes and is not necessary for catecholamine secretion. The distinct functions of ClC-3c and ClC-3b illustrate the impact of expressing multiple CLC transporters with similar transport functions and separate localizations in different endosomal compartments.


Assuntos
Células Cromafins , Prótons , Animais , Catecolaminas/metabolismo , Cloretos/metabolismo , Células Cromafins/metabolismo , Exocitose/fisiologia , Mamíferos , Camundongos , Camundongos Knockout , Vesículas Secretórias/metabolismo
20.
Dokl Biochem Biophys ; 502(1): 36-39, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35275304

RESUMO

The  effect  of  adrenaline  in  various  concentrations  and  dopamine  at  a  concentration  of 10-10 mol/mL on the behavior of Paramecium caudatum was studied. It is shown that adrenaline reduces motor activity and changes the movement strategy of these protozoans; a dose-dependent behavioral response on the drug concentration was observed. This effect can be explained by the presence of adrenaline receptors located on the surface of the cell membrane. To study the direct effect of adrenaline on alpha and beta adrenergic receptors, the effect of non-selective adrenoblockers nicergoline and timolol is considered in this paper. At the same time, dopamine at a concentration of 10-10 mol/mL does not have a significant effect on the nature and magnitude of motor activity during the entire registration time, since this organism does not have receptors for this mediator. The proposed method makes it possible to quickly and objectively assess the nature of the effects of various pharmaceuticals acting on the catecholamine system.


Assuntos
Paramecium caudatum , Catecolaminas , Epinefrina/farmacologia , Células Eucarióticas , Preparações Farmacêuticas
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