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1.
Biochim Biophys Acta Mol Basis Dis ; 1870(5): 167209, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38701955

ABSTRACT

FOLFOX is a combination of chemotherapeutic agents (5-fluorouracil, leucovorin, and oxaliplatin) and is used to treat advanced colorectal cancer (CRC) but induces various side effects. Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most critical side effects that compromise the quality of life of patients with CRC undergoing FOLFOX chemotherapy. This study aimed to evaluate circulating miRNA, cortisol and catecholamine as potential biomarkers that can predict FOLFOX-CIPN symptoms. High-throughput microRNA (miRNA) sequencing was performed on the RNA circulating in the plasma of eight patients with CRC who underwent FOLFOX chemotherapy. miRNA expression profiles were evaluated according to two groups: those who underwent ≤3 cycles and those who underwent ≥6 cycles of FOLFOX chemotherapy. The identified miRNAs were validated in 27 patients with CRC who underwent FOLFOX chemotherapy using quantitative reverse transcription polymerase chain reaction. Target genes were predicted using bioinformatics and functional analyses. Cortisol and catecholamine concentrations in peripheral plasma were measured using an enzyme-linked immunosorbent assay. miR-3184-5p was differentially expressed when miRNA expression was compared between the groups that underwent ≤3 and ≥6 cycles of FOLFOX chemotherapy. Cortisol levels were significantly higher in the group that underwent ≥6 cycles of FOLFOX chemotherapy than in the group that underwent ≤3 cycles. This study suggests that miR-3184-5p may be a potential marker for predicting CIPN.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Colorectal Neoplasms , Fluorouracil , Leucovorin , MicroRNAs , Organoplatinum Compounds , Peripheral Nervous System Diseases , Humans , Leucovorin/therapeutic use , Leucovorin/adverse effects , Peripheral Nervous System Diseases/chemically induced , Peripheral Nervous System Diseases/genetics , Peripheral Nervous System Diseases/blood , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/genetics , Colorectal Neoplasms/blood , Fluorouracil/adverse effects , Fluorouracil/therapeutic use , Male , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Female , Middle Aged , Organoplatinum Compounds/adverse effects , Organoplatinum Compounds/therapeutic use , MicroRNAs/blood , MicroRNAs/genetics , Aged , Hydrocortisone/blood , Biomarkers, Tumor/genetics , Biomarkers, Tumor/blood , Adult , Catecholamines/blood
2.
J Appl Physiol (1985) ; 136(5): 1040-1052, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38205550

ABSTRACT

Findings from a recent 70-day bedrest investigation suggested intermittent exercise testing in the control group may have served as a partial countermeasure for skeletal muscle size, function, and fiber-type shifts. The purpose of the current study was to investigate the metabolic and skeletal muscle molecular responses to the testing protocols. Eight males (29 ± 2 yr) completed muscle power (6 × 4 s; peak muscle power: 1,369 ± 86 W) and V̇o2max (13 ± 1 min; 3.2 ± 0.2 L/min) tests on specially designed supine cycle ergometers during two separate trials. Blood catecholamines and lactate were measured pre-, immediately post-, and 4-h postexercise. Muscle homogenate and muscle fiber-type-specific [myosin heavy chain (MHC) I and MHC IIa] mRNA levels of exercise markers (myostatin, IκBα, myogenin, MuRF-1, ABRA, RRAD, Fn14, PDK4) and MHC I, IIa, and IIx were measured from vastus lateralis muscle biopsies obtained pre- and 4-h postexercise. The muscle power test altered (P ≤ 0.05) norepinephrine (+124%), epinephrine (+145%), lactate (+300%), and muscle homogenate mRNA (IκBα, myogenin, MuRF-1, RRAD, Fn14). The V̇o2max test altered (P ≤ 0.05) norepinephrine (+1,394%), epinephrine (+1,412%), lactate (+736%), and muscle homogenate mRNA (myostatin, IκBα, myogenin, MuRF-1, ABRA, RRAD, Fn14, PDK4). In general, both tests influenced MHC IIa muscle fibers more than MHC I with respect to the number of genes that responded and the magnitude of response. Both tests also influenced MHC mRNA expression in a muscle fiber-type-specific manner. These findings provide unique insights into the adaptive response of skeletal muscle to small doses of exercise and could help shape exercise dosing for astronauts and Earth-based individuals.NEW & NOTEWORTHY Declines in skeletal muscle health are a concern for astronauts on long-duration spaceflights. The current findings add to the growing body of exercise countermeasures data, suggesting that small doses of specific exercise can be beneficial for certain aspects of skeletal muscle health. This information can be used in conjunction with other components of existing exercise programs for astronauts and might translate to other areas focused on skeletal muscle health (e.g., sports medicine, rehabilitation, aging).


Subject(s)
Exercise , Muscle, Skeletal , Space Flight , Humans , Male , Space Flight/methods , Adult , Muscle, Skeletal/metabolism , Muscle, Skeletal/physiology , Exercise/physiology , Myosin Heavy Chains/metabolism , Lactic Acid/blood , Lactic Acid/metabolism , RNA, Messenger/metabolism , Catecholamines/metabolism , Catecholamines/blood , Exercise Test/methods , Oxygen Consumption/physiology , Muscle Proteins/metabolism
3.
Diabetes ; 71(3): 538-553, 2022 03 01.
Article in English | MEDLINE | ID: mdl-34862200

ABSTRACT

Pancreastatin (PST), a chromogranin A-derived potent physiological dysglycemic peptide, regulates glucose/insulin homeostasis. We have identified a nonsynonymous functional PST variant (p.Gly297Ser; rs9658664) that occurs in a large section of human populations. Association analysis of this single nucleotide polymorphism with cardiovascular/metabolic disease states in Indian populations (n = 4,300 subjects) displays elevated plasma glucose, glycosylated hemoglobin, diastolic blood pressure, and catecholamines in Gly/Ser subjects as compared with wild-type individuals (Gly/Gly). Consistently, the 297Ser allele confers an increased risk (∼1.3-1.6-fold) for type 2 diabetes/hypertension/coronary artery disease/metabolic syndrome. In corroboration, the variant peptide (PST-297S) displays gain-of-potency in several cellular events relevant for cardiometabolic disorders (e.g., increased expression of gluconeogenic genes, increased catecholamine secretion, and greater inhibition of insulin-stimulated glucose uptake) than the wild-type peptide. Computational docking analysis and molecular dynamics simulations show higher affinity binding of PST-297S peptide with glucose-regulated protein 78 (GRP78) and insulin receptor than the wild-type peptide, providing a mechanistic basis for the enhanced activity of the variant peptide. In vitro binding assays validate these in silico predictions of PST peptides binding to GRP78 and insulin receptor. In conclusion, the PST 297Ser allele influences cardiovascular/metabolic phenotypes and emerges as a novel risk factor for type 2 diabetes/hypertension/coronary artery disease in human populations.


Subject(s)
Cardiovascular Diseases/genetics , Chromogranin A/genetics , Genetic Predisposition to Disease/genetics , Metabolic Diseases/genetics , Amino Acid Sequence , Animals , Catecholamines/blood , Cell Line , Cell Line, Tumor , Chromogranin A/chemistry , Chromogranin A/metabolism , Coronary Artery Disease/genetics , Diabetes Mellitus, Type 2/genetics , Endoplasmic Reticulum Chaperone BiP/metabolism , Genetic Association Studies/methods , Hep G2 Cells , Humans , Hypertension/genetics , India , Peptides/chemistry , Peptides/genetics , Peptides/metabolism , Polymorphism, Single Nucleotide/genetics , Rats , Receptor, Insulin/metabolism
4.
Eur J Pharmacol ; 914: 174668, 2022 Jan 05.
Article in English | MEDLINE | ID: mdl-34863997

ABSTRACT

BACKGROUND: Sepsis often results in acute lung injury (ALI). Dexmedetomidine (Dex) was reported to protect cells and organs due to its direct cellular effects. This study aims to investigate the role of vagus nerves on Dex induced lung protection in lipopolysaccharide (LPS)-induced ALI rats. METHODS: The bilateral cervical vagus nerve of male Sprague-Dawley rats was sectioned or just exposed as sham surgery. After LPS administration, Dex antagonist yohimbine (YOH) and/or Dex was injected intraperitoneally to rats with or without vagotomy. The severity of ALI was determined with survival curve analysis and lung pathological scores. The plasma concentrations of interleukin 1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), catecholamine and acetylcholine were measured with enzyme-linked immunosorbent assay. RESULTS: The median survival time of LPS-induced ALI rats was prolonged by Dex (22 h, 95% CI, [24.46, 92.20]) vs. 14 h, 95% CI, [14.60, 89.57] of the LPS control group, P < 0.05), and the ALI score was reduced by Dex (6.5, 95% CI, [5.23, 8.10] vs. 11.5, 95% CI, [10.23, 13.10] in the LPS group, P < 0.01). However, these protective effects were significantly decreased by either YOH administration or vagotomy. Dex decreased LPS-induced IL-1ß, TNF-α, and catecholamine but increased acetylcholine in blood serum; these effects of Dex was partially abolished by vagotomy. CONCLUSIONS: Our data suggested that Dex increased vagal nerve tone that partially contributed to its anti-inflammatory and lung-protective effects. The indirect anti-inflammation and direct cytoprotection of Dex are likely through high vagal nerve tone and α2-adrenoceptor activation, respectively.


Subject(s)
Acute Lung Injury , Dexmedetomidine/pharmacology , Lung , Sepsis/complications , Vagotomy/methods , Vagus Nerve/surgery , Acetylcholine/blood , Acute Lung Injury/etiology , Acute Lung Injury/metabolism , Acute Lung Injury/pathology , Adrenergic alpha-2 Receptor Agonists/pharmacology , Animals , Anti-Inflammatory Agents/pharmacology , Catecholamines/blood , Interleukin-1beta/blood , Lung/immunology , Lung/pathology , Protective Agents/pharmacology , Rats , Rats, Sprague-Dawley , Treatment Outcome , Tumor Necrosis Factor-alpha/blood
5.
Medicine (Baltimore) ; 100(46): e27888, 2021 Nov 19.
Article in English | MEDLINE | ID: mdl-34797335

ABSTRACT

RATIONALE: Paraganglioma (PGL), an extra-adrenal pheochromocytoma, is a rare tumor, especially in children. While hypersecretion of catecholamines causes the classic triad of headaches, palpitations, and profuse sweating, prompt diagnosis is still challenging. PATIENT CONCERNS: For 7 months, an 8-year-old boy complained of polyuria and weight loss, followed by proteinuria and headache for 1 month prior to admission. He was admitted to our hospital due to an afebrile seizure. DIAGNOSIS: His blood pressure remained markedly elevated even after cessation of the convulsion. Magnetic resonance imaging of the brain revealed posterior reversible encephalopathy syndrome. Abdominal computed tomography showed a mass lesion encasing the left renal artery, measuring 41 mm in length along its major axis. The plasma and urine levels of normetanephrine were elevated. Additionally, iodine-123-metaiodobenzylguanidine scintigraphy showed an abnormal uptake in the abdominal mass with no evidence of metastasis. Based on these findings, we tentatively diagnosed him with PGL. INTERVENTION: Substantial alpha- and beta-blocking procedures were performed, followed by a tumor resection and an extended left nephrectomy on day 31 of hospitalization. Pathological findings confirmed the diagnosis of PGL. OUTCOME: The postoperative course was uneventful, and his blood pressure normalized without the use of antihypertensive agents. Genetic testing revealed a known SDHB germline mutation. The same mutation was also detected on his father and paternal grandfather without any history of hypertension or malignant tumor. LESSON: It remains challenging to diagnose pheochromocytoma/paraganglioma (PPGL) promptly because PPGL can present with a variety of symptoms. Preceding symptoms of the presented case might be caused by PGL. Although PPGL is a rare disease, especially in children, it should be considered in differential diagnosis when various unexplained symptoms persist.


Subject(s)
Adrenal Gland Neoplasms , Catecholamines/blood , Paraganglioma/genetics , Pheochromocytoma , Posterior Leukoencephalopathy Syndrome , 3-Iodobenzylguanidine , Child , Headache/etiology , Humans , Male , Paraganglioma/diagnosis , Paraganglioma/surgery , Pheochromocytoma/diagnosis , Pheochromocytoma/genetics , Pheochromocytoma/surgery , Polyuria/etiology , Proteinuria/etiology , Radionuclide Imaging , Weight Loss
6.
Scand J Clin Lab Invest ; 81(7): 564-572, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34570657

ABSTRACT

BACKGROUND: Accurate diagnosis of pheochromocytoma and paraganglioma (PPGLs) is highly dependent on the detection of metanephrines and catecholamines. However, the systematic investigation on influencing factors including specimen (plasma or whole blood), anticoagulant, storage conditions, and interference factors need further confirmation. METHODS: Blood with heparin-lithium or EDTA-K2 were collected, stability of epinephrine (EPI), norepinephrine (NE), dopamine (DA), metanephrine (MN), normetanephrine (NMN), 3-methoxytyramine (3-MT) in whole blood and plasma at room temperature and 4 °C for different storage times, stability of plasma MN, NMN and 3-MT at -20 °C and -80 °C were investigated. Plasma with hemoglobin (1 g/L, 2 g/L, 3 g/L, 4 g/L, 6 g/L), TG (<5 mmol/L, 5-8 mmol/L, >8 mmol/L) were prepared. RESULTS: EPI, NE, DA were prone to degrade at room temperature, samples should be centrifuged at 4 °C. EPI and NE were stable in whole blood at 4 °C for 4 h and in plasma for 2 h. For MN, NMN, 3-MT, plasma can be stable at room temperature and 4 °C for at least 6 h, which is better than whole blood; there was no significant difference when stored at -20 °C and -80 °C for 7 days. Heparin-lithium had a slight advantage over EDTA-K2. EPI, NE, DA should not be performed when Hb > 1 g/L or TG > 5 mmol/L. MN, NMN, 3-MT should not be performed when Hb > 2 g/L, whereas TG had no interference. CONCLUSIONS: According to the actual clinical application scenario, this study provided a reliable basis for the accurate diagnosis of PPGLs.


Subject(s)
Adrenal Gland Neoplasms/diagnosis , Catecholamines/blood , Dopamine/analogs & derivatives , Metanephrine/blood , Paraganglioma/diagnosis , Pheochromocytoma/diagnosis , Adrenal Gland Neoplasms/blood , Anticoagulants/pharmacology , Dopamine/blood , Epinephrine/blood , Hemoglobins/analysis , Humans , Metabolome , Norepinephrine/blood , Normetanephrine/blood , Paraganglioma/blood , Pheochromocytoma/blood , Triglycerides/blood
7.
Gynecol Endocrinol ; 37(8): 753-757, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34060419

ABSTRACT

AIMS: To investigate the change of stress hormones, oxidative stress and insulin resistance (IR) in women with gestational diabetes mellitus (GDM) after supplement whey protein, in an attempt to gain insights into the prevention and treatment of GDM. MATERIALS AND METHODS: 60 GDM women were recruited in this study, and 30 women received a preload drink containing 20 g whey protein as group GDM-W, and the other 30 women received control flavoring drink as group GDM, and the trial lasted for 14 days. Plasma epinephrine (E), noradrenaline (NE), and cortisol were detected; we also determined levels of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH). Homeostasis model assessment of insulin resistance (HOMA-IR) was used to assess IR. RESULTS: In the GDM-W group, postprandial blood glucose was decreased significantly on 3, 5, 7, and 14 days (all p < .05), plasma 2 h insulin was increased by 7.2, 8.6, and 20.5% on days 5, 7, and 14 (p < .05, .05, .01). HOMA-IR was decreased significantly on day 14 (p < .05). MDA was decreased by 20.7% on day 14 (p < .01), and anti-oxidative enzymes' SOD was decreased by 13.4% on day 14 (p < .05) and GSH was decreased by 16.7 and 29.1% on days 7 and 14 (both p < .05). Stress hormones E and cortisol were decreased by 10.8 and 19.8%, respectively, on day 14 (p < .05). There was no significant difference in NE between the two groups within 14 days. CONCLUSIONS: Whey protein supplementation may improve hyperglycemia by alleviating stress disorder and oxidative stress injury in GDM women. This trial was registered at chictr.org.cn/as ChiCTR1800020413.


Subject(s)
Catecholamines/blood , Diabetes, Gestational/diet therapy , Hydrocortisone/blood , Hyperglycemia/drug therapy , Oxidative Stress/drug effects , Whey Proteins/administration & dosage , Adult , Blood Glucose/analysis , Diabetes, Gestational/blood , Diabetes, Gestational/physiopathology , Epinephrine/blood , Female , Gestational Age , Glutathione/blood , Humans , Insulin Resistance , Malondialdehyde/blood , Norepinephrine/blood , Pregnancy , Superoxide Dismutase/blood
8.
J Clin Endocrinol Metab ; 106(10): e4028-e4038, 2021 09 27.
Article in English | MEDLINE | ID: mdl-34089611

ABSTRACT

CONTEXT: Pheochromocytomas and paragangliomas (PCC/PGL) are neuroendocrine tumors with discrete catecholamine profiles that cause incompletely understood metabolic and physiologic changes. OBJECTIVE: The objective was to evaluate relationships between plasma catecholamines, body weight, and hemoglobin A1c (HbA1c). We hypothesized that individual catecholamines would correlate negatively with weight and glucose control. DESIGN: A retrospective cohort study was performed (1999-2020). Wilcoxon rank-sum tests compared nonparametric, continuous variables; mixed-effect linear modeling (MEM) evaluated relationships between catecholamines and weight or HbA1c. The median study duration was 54.2 months [interquartile range (IQR) 19.0-95.1]. SETTING: Tertiary academic hospital. PATIENTS: 360 patients were identified prospectively by referral to our center for management or surveillance of PCC/PGL. The median age was 59 years (IQR 45-67) and 56.4% (n = 203) were female. MAIN OUTCOME MEASURES: The primary and secondary outcomes were weight and HbA1c, respectively. RESULTS: On multivariable MEM, norepinephrine (P < 0.0005) negatively correlated with weight when all catecholamines and their derivatives were tried in the model, and normetanephrine (P < 0.0005) correlated when only metanephrines were included. In the surgical cohort (n = 272), normetanephrine decreased postoperatively and was inversely associated with weight (P < 0.0005). Elevated norepinephrine or normetanephrine at the study termination, indicative of metastatic and/or recurrent disease (MRD), correlated with weight loss. Norepinephrine and normetanephrine (P < 0.0005) directly correlated with HbA1c. CONCLUSION: Plasma norepinephrine and its metabolite directly correlate with HbA1c and inversely correlate with weight in PCC/PGL. After resection, declining normetanephrine levels correlate with improving HbA1c despite an increase in patient body weight. Persistently elevated catecholamines and decreasing weight are observed in MRD.


Subject(s)
Adrenal Gland Neoplasms , Body Weight/physiology , Catecholamines/blood , Diabetes Mellitus/epidemiology , Paraganglioma , Pheochromocytoma , Adrenal Gland Neoplasms/blood , Adrenal Gland Neoplasms/complications , Adrenal Gland Neoplasms/epidemiology , Aged , Cohort Studies , Diabetes Mellitus/blood , Diabetes Mellitus/etiology , Female , Glycated Hemoglobin/metabolism , Humans , Male , Middle Aged , Obesity/blood , Obesity/epidemiology , Obesity/etiology , Paraganglioma/blood , Paraganglioma/complications , Paraganglioma/epidemiology , Pheochromocytoma/blood , Pheochromocytoma/complications , Pheochromocytoma/epidemiology , Retrospective Studies , Risk Factors , United States/epidemiology
9.
J Endocrinol ; 249(3): 195-207, 2021 05 13.
Article in English | MEDLINE | ID: mdl-33994373

ABSTRACT

Fetuses with intrauterine growth restriction (IUGR) have high concentrations of catecholamines, which lowers the insulin secretion and glucose uptake. Here, we studied the effect of hypercatecholaminemia on glucose metabolism in sheep fetuses with placental insufficiency-induced IUGR. Norepinephrine concentrations are elevated throughout late gestation in IUGR fetuses but not in IUGR fetuses with a bilateral adrenal demedullation (IAD) at 0.65 of gestation. Euglycemic (EC) and hyperinsulinemic-euglycemic (HEC) clamps were performed in control, intact-IUGR, and IAD fetuses at 0.87 of gestation. Compared to controls, basal oxygen, glucose, and insulin concentrations were lower in IUGR groups. Norepinephrine concentrations were five-fold higher in IUGR fetuses than in IAD fetuses. During the EC, rates of glucose entry (GER, umbilical + exogenous), glucose utilization (GUR), and glucose oxidation (GOR) were greater in IUGR groups than in controls. In IUGR and IAD fetuses with euglycemia and euinsulinemia, glucose production rates (GPR) remained elevated. During the HEC, GER and GOR were not different among groups. In IUGR and IAD fetuses, GURs were 40% greater than in controls, which paralleled the sustained GPR despite hyperinsulinemia. Glucose-stimulated insulin concentrations were augmented in IAD fetuses compared to IUGR fetuses. Fetal weights were not different between IUGR groups but were less than controls. Regardless of norepinephrine concentrations, IUGR fetuses not only develop greater peripheral insulin sensitivity for glucose utilization but also develop hepatic insulin resistance because GPR was maintained and unaffected by euglycemia or hyperinsulinemia. These findings show that adaptation in glucose metabolism of IUGR fetuses are independent of catecholamines, which implicate that hypoxemia and hypoglycemia cause the metabolic responses.


Subject(s)
Catecholamines/metabolism , Fetal Growth Retardation/veterinary , Glucose/metabolism , Norepinephrine/metabolism , Adrenal Glands/pathology , Animals , Biological Transport , Blood Glucose , Catecholamines/blood , Female , Fetal Development , Fetus , Norepinephrine/blood , Placental Insufficiency/metabolism , Pregnancy , Sheep
10.
Biomolecules ; 11(3)2021 02 24.
Article in English | MEDLINE | ID: mdl-33668381

ABSTRACT

Syndecans (SDCs) are transmembrane proteins that are present on most cell types where they play a role in multiple physiological processes, including cell-matrix adhesion and inflammation. Growing evidence suggests that elevated levels of both shed SDC1 and SDC4 are associated with hypertension and cardiovascular diseases, but their relationships with cardiovascular risk factors in healthy individuals are unknown. The primary objective of this study was to investigate whether serum levels of SDC4 and SDC1 were associated with body composition, hemodynamic parameters, pro-inflammatory cytokine concentrations, and urinary noradrenaline and dopamine levels in healthy women (17 African American and 20 European American) between the ages of 20 and 40 years old. Univariate analyses revealed only a significant (p < 0.05) inverse correlation between serum SDC1 and body fat percentage. On the other hand, serum SDC4 was positively correlated with systolic blood pressure, diastolic blood pressure, and urinary levels of noradrenaline and dopamine. Serum SDC4 was also a significant predictor of systolic blood pressure in a multivariate regression model that included fat-free mass and urinary dopamine levels as significant independent variables. The result did not change even adjusting for race. Our findings indicate that SDC4 has an important role in the physiological regulation of blood pressure.


Subject(s)
Heparan Sulfate Proteoglycans/blood , Hypertension/blood , Adult , Body Composition/physiology , Catecholamines/blood , Dopamine/blood , Female , Humans , Norepinephrine/blood , Premenopause , Syndecan-4/blood , Young Adult
11.
Medicine (Baltimore) ; 100(11): e24984, 2021 Mar 19.
Article in English | MEDLINE | ID: mdl-33725969

ABSTRACT

INTRODUCTION: Pheochromocytoma (PHEO)-related cardiomyopathy is a rare condition in which release of a large amount of catecholamines leads to severe vasoconstriction, coronary vasospasm, myocardial ischemia, injury, and necrosis. Its clinical manifestations can be similar to those of acute coronary syndrome. PATIENT CONCERNS: A 63-year-old woman was diagnosed with acute non-ST segment elevation myocardial infarction following chest pain for 8 hours. The results of coronary angiography were normal. The patient developed dyspnea, cough with frothy pink sputum, paroxysmal sweating, arrhythmia, and blood pressure fluctuation, and was transferred to the intensive care unit for monitoring and treatment. DIAGNOSIS: PHEO, catecholamine cardiomyopathy (CICMP). INTERVENTION: After monitoring the pulse index continuous cardiac output and treatment with α and ß adrenergic receptor blockers for 18 days, laparoscopic resection of the left adrenal mass was performed. OUTCOMES: The patient's condition improved and she was discharged 31 days after admission. Outpatient follow-up examinations 1 month and 1 year later did not show recurrence. LESSONS: PHEO can cause CICMP, the manifestations of which are partly similar to those of takotsubo cardiomyopathy (TTC). Once the patient's condition stabilizes, surgery should be considered. Fluid management is necessary, and agents such as α and ß adrenergic receptor blockers should be administered.


Subject(s)
Adrenal Gland Neoplasms/complications , Cardiomyopathies/etiology , Non-ST Elevated Myocardial Infarction/etiology , Pheochromocytoma/complications , Acute Disease , Adrenal Gland Neoplasms/blood , Adrenal Gland Neoplasms/diagnosis , Cardiomyopathies/blood , Cardiomyopathies/diagnosis , Catecholamines/blood , Diagnosis, Differential , Female , Humans , Middle Aged , Non-ST Elevated Myocardial Infarction/diagnosis , Pheochromocytoma/blood , Pheochromocytoma/diagnosis
12.
Life Sci Space Res (Amst) ; 28: 66-73, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33612181

ABSTRACT

Deep-space missions may alter immune cell phenotype in the primary (e.g., thymus) and secondary (e.g., spleen) lymphoid organs contributing to the progression of a variety of diseases. In deep space missions, astronauts will be exposed to chronic low doses of HZE radiation while being in microgravity. Ground-based models of long-term uninterrupted exposures to HZE radiation are not yet available. To obtain insight in the effects of concurrent exposure to microgravity and chronic irradiation (CIR), mice received a cumulative dose of chronic 0.5 Gy gamma rays over one month ± simulated microgravity (SMG). To obtain insight in a dose rate effect, additional mice were exposed to single acute irradiation (AIR) at 0.5 Gy gamma rays. We measured proportions of immune cells relative to total number of live cells in the thymus and spleen, stress level markers in plasma, and change in body weight, food consumption, and water intake. CIR affected thymic CD3+/CD335+ natural killer T (NK-T) cells, CD25+ regulatory T (Treg) cells, CD27+/CD335- natural killer (NK1) cells and CD11c+/CD11b- dendritic cells (DCs) differently in mice subjected to SMG than in mice with normal loading. No such effects of CIR on SMG as compared to normal loading were observed in cell types from the spleen. Differences between CIR and AIR groups (both under normal loading) were found in thymic Treg and DCs. Food consumption, water intake, and body weight were less after coexposure than singular or no exposure. Compared to sham, all treatment groups exhibited elevated plasma levels of the stress marker catecholamines. These data suggest that microgravity and chronic irradiation may interact with each other to alter immune cell phenotypes in an organ-specific manner and appropriate strategies are required to reduce the health risk of crewmembers.


Subject(s)
Gamma Rays/adverse effects , Spleen/radiation effects , Thymus Gland/radiation effects , Weightlessness Simulation/adverse effects , Animals , Body Weight , Catecholamines/blood , Dose-Response Relationship, Radiation , Drinking , Energy Intake , Male , Mice, Inbred C57BL , Spleen/cytology , Spleen/immunology , Stress, Physiological , Thymus Gland/cytology , Thymus Gland/immunology
13.
Endocr Regul ; 55(1): 16-21, 2021 Jan 29.
Article in English | MEDLINE | ID: mdl-33600666

ABSTRACT

Objectives. Pheochromocytoma (PCC) is a neuroendocrine tumor derived from chromaffin tissue more frequently found in the adrenal medulla. Many discoveries over the last decade have significantly improved our understanding of PCC.Methods. We retrospectively reviewed all patients with a histological diagnosis of PCC at the Centro Hospitalar Universitario de Sao Joao, a tertiary and university hospital in Oporto, Portugal, between January 2009 and December 2017.Results. The study group included 33 patients. In most cases the diagnosis was suspected with more than half of patients presenting with hypertension and the third diagnosed during the work-up of an adrenal incidentaloma. About half of the patients was referred for genetic testing and 6 patients had a positive inherited susceptibility genetic pathogenic variant associated with classic cancer predisposition syndromes and also associated with newly described genes. In the incidentaloma group, genetic testing was performed in 3 (9%) patients with only 1 positive result. In the suspected group, 15 (45%) genetic tests were performed.Conclusions. In contrast to other studies, where only a minority of patients with PCC were referred for genetic counselling, in our study 54% of patients was referred for genetic testing. This study suggests that clinicians were correctly recognizing the need to refer young patients and patients with positive family history. However, opportunities for genetic testing are frequently missed due to low referral rates in patients with apparently sporadic PCC, particularly older than 30 years old. It is imperative that all the providers involved in the multidisciplinary care of patients with pheochromocytomas are aware of the genetic disorders associated with these unique tumors.


Subject(s)
Adrenal Gland Neoplasms/diagnosis , Adrenal Gland Neoplasms/genetics , Pheochromocytoma/diagnosis , Pheochromocytoma/genetics , Adult , Aged , Catecholamines/blood , Catecholamines/urine , Chromogranin A/blood , Female , Genetic Predisposition to Disease , Genetic Testing , Humans , Hypertension , Male , Middle Aged , Paraganglioma/diagnosis , Paraganglioma/genetics , Retrospective Studies
14.
J Am Coll Cardiol ; 77(7): 902-921, 2021 02 23.
Article in English | MEDLINE | ID: mdl-33602474

ABSTRACT

Takotsubo syndrome (TTS) has been a recognized clinical entity for 31 years, since its first description in 1990. TTS is now routinely diagnosed in patients who present with acute chest pain, electrocardiographic changes, troponin elevation, unobstructed coronary arteries, and a typical pattern of circumferential left ventricular wall motion abnormalities that usually involve the apical and midventricular myocardium. Increasing understanding of this intriguing syndrome stems from wider recognition, possible increasing frequency, and a rising number of publications focused on the pathophysiology in clinical and laboratory studies. A comprehensive understanding of TTS pathophysiology and evidence-based treatments are lacking, and specific and effective treatments are urgently required. This paper reviews the pathophysiology of this fascinating syndrome; what is known from both clinical and preclinical studies, including review of the evidence for microvascular dysfunction, myocardial beta-adrenergic signaling, inflammation, and electrophysiology; and where focused research needs to fill gaps in understanding TTS.


Subject(s)
Takotsubo Cardiomyopathy/physiopathology , Arrhythmias, Cardiac/physiopathology , Autonomic Nervous System/physiopathology , Catecholamines/blood , Coronary Circulation/physiology , Humans , Microcirculation/physiology , Myocarditis/diagnostic imaging , Myocarditis/physiopathology , Myocardium/metabolism , Myocytes, Cardiac/physiology , Sex Factors , Stress, Physiological/physiology , Stress, Psychological/physiopathology , Sympathetic Nervous System/physiology , Takotsubo Cardiomyopathy/blood
15.
Physiol Rep ; 9(3): e14718, 2021 02.
Article in English | MEDLINE | ID: mdl-33580902

ABSTRACT

BACKGROUND: Sympathetic activity causes changes in electrocardiogram (ECG) during cold exposure and the changes have been studied mostly during hypothermia and less during mild acute nonshivering cold exposure. Cold-induced sympathetic activity also activates brown adipose tissue (BAT) and increases arterial blood pressure (BP) and plasma catecholamine levels. We examined changes in ECG parameters during acute nonshivering cold exposure and their associations with markers of sympathetic activity during cold exposure: brachial blood pressure (BP), plasma catecholamine levels, and BAT activity measured by positron emission tomography (PET). METHODS AND RESULTS: Healthy subjects (M/F = 13/24, aged 20-55 years) were imaged with [15 O]H2 O (perfusion, N = 37) and [18 F]FTHA to measure plasma nonesterified fatty acid uptake (NEFA uptake, N = 37) during 2-h nonshivering cold exposure. 12-lead ECG (N = 37), plasma catecholamine levels (N = 17), and brachial BP (N = 31) were measured at rest in room temperature (RT) and re-measured after a 2-h nonshivering cold exposure. There were significant differences between RT and cold exposure in P axis (35.6 ± 26.4 vs. 50.8 ± 22.7 degrees, p = 0.005), PR interval (177.7 ± 24.6 ms vs.163.0 ± 28.7 ms, p = 0.001), QRS axis (42.1 ± 31.3 vs. 56.9 ± 24.1, p = 0.003), and QT (411.7 ± 25.5 ms vs. 434.5 ± 39.3 ms, p = 0.001). There was no significant change in HR, QRS duration, QTc, JTc, and T axis during cold exposure. Systolic BP (127.2 ± 15.7 vs. 131.8 ± 17.9 mmHg, p = 0.008), diastolic BP (81.7 ± 12.0 vs. 85.4 ± 13.0 mmHg, p = 0.02), and plasma noradrenaline level increased during cold exposure (1.97 ± 0.61 vs. 5.07 ± 1.32 µmol/L, p = 0.001). Cold-induced changes in ECG parameters did not correlate with changes in BAT activity, brachial BP, plasma catecholamines, or skin temperature. CONCLUSIONS: During short-term nonshivering cold exposure, there were increases in P axis, PR interval, QRS axis, and QT compared to RT in healthy adults. Cold-induced changes in ECG parameters did not correlate with BAT activity, brachial BP, or plasma catecholamine levels which were used as markers of cold-induced sympathetic activity.


Subject(s)
Adipose Tissue, Brown/innervation , Arterial Pressure , Brachial Artery/innervation , Catecholamines/blood , Cold Temperature , Electrocardiography , Healthy Volunteers , Heart Rate , Sympathetic Nervous System/physiology , Adaptation, Physiological , Adipose Tissue, Brown/diagnostic imaging , Adipose Tissue, Brown/metabolism , Adult , Female , Humans , Male , Middle Aged , Positron Emission Tomography Computed Tomography , Sympathetic Nervous System/metabolism , Time Factors , Young Adult
16.
Blood Press ; 30(3): 154-164, 2021 06.
Article in English | MEDLINE | ID: mdl-33399016

ABSTRACT

PURPOSE: Sympathetic nervous system (SNS) over-activity is associated with essential hypertension. Renal sympathetic denervation (RDN) possibly lowers office- and ambulatory blood pressure (BP) in patients with treatment-resistant hypertension (TRH). We aimed to assess the effect of RDN compared to drug adjustment on SNS activity among patients with TRH by measuring plasma catecholamines and heart rate variability (HRV) during stress tests. MATERIALS AND METHODS: Patients with TRH were randomised to RDN (n = 9) or Drug Adjustment (DA) (n = 10). We measured continuous HRV and beat-to-beat-BP using FinaPres® and obtained plasma catecholamines during standardised orthostatic- and cold-pressor stress tests (CPT) before- and six months after randomisation. RESULTS: CPT revealed no differences between groups at baseline in peak adrenaline concentration (69.3 pg/mL in the DA group vs. 70.0 pg/mL in the RDN group, p = 0.38) or adrenaline reactivity (Δ23.1 pg/mL in the DA group vs. Δ29.3 pg/mL in the RDN group, p = 0.40). After six months, adrenaline concentrations were statistically different between groups after one minute (66.9 pg/mL in the DA group vs. 55.3 pg/mL in the RDN group, p = 0.03), and six minutes (62.4 pg/mL in the DA group vs. 50.1 pg/mL in the RDN group, p = 0.03). There was a tendency of reduction in adrenaline reactivity after six months in the RDN group (Δ26.3 pg/mL at baseline vs. Δ12.8 pg/ml after six months, p = 0.08), while it increased in the DA group (Δ13.6 pg/mL at baseline vs. Δ19.9 pg/mL after six months, p = 0.53). We also found a difference in the Low Frequency band at baseline following the CPT (667µs2 in the DA group vs. 1628µs2 in the RDN group, p = 0.03) with a clear tendency of reduction in the RDN group to 743µs2 after six months (p = 0.07), compared to no change in the DA group (1052µs2,p = 0.39). CONCLUSION: Our data suggest that RDN reduces SNS activity after six months. This finding warrants investigation in a larger study. Clinical Trial Number registered at www.clinicaltrials.gov: NCT01673516.


Subject(s)
Autonomic Denervation , Catecholamines/blood , Essential Hypertension , Kidney , Sympathetic Nervous System , Aged , Essential Hypertension/blood , Essential Hypertension/physiopathology , Essential Hypertension/therapy , Exercise Test , Female , Humans , Kidney/innervation , Kidney/metabolism , Kidney/physiopathology , Male , Middle Aged , Norway , Sympathetic Nervous System/metabolism , Sympathetic Nervous System/physiopathology
17.
Acta Cardiol ; 76(4): 396-401, 2021 Jun.
Article in English | MEDLINE | ID: mdl-32223369

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.


Subject(s)
Aminobutyrates/therapeutic use , Angiotensin Receptor Antagonists/therapeutic use , Biphenyl Compounds/therapeutic use , Catecholamines/blood , Heart Failure , Valsartan/therapeutic use , Drug Combinations , Follow-Up Studies , Heart Failure/drug therapy , Humans , Stroke Volume , Treatment Outcome
18.
Med Sci Sports Exerc ; 53(5): 1056-1067, 2021 05 01.
Article in English | MEDLINE | ID: mdl-33065594

ABSTRACT

PURPOSE: The study aimed to determine the effect of diurnal versus nocturnal exercise on gastrointestinal integrity and functional responses, plasma lipopolysaccharide binding protein (LBP) and soluble CD14 (sCD14) concentrations (as indirect indicators of endotoxin responses), systemic inflammatory cytokine profile, gastrointestinal symptoms, and feeding tolerance. METHODS: Endurance runners (n = 16) completed 3 h of 60% V˙O2max (22.7°C, 45% relative humidity) running, on one occasion performed at 0900 h (400 lx; DAY) and on another occasion at 2100 h (2 lx; NIGHT). Blood samples were collected pre- and postexercise and during recovery to determine plasma concentrations of cortisol, catecholamines, claudin-3, I-FABP, LBP, and sCD14 and inflammatory cytokine profiles by ELISA. Orocecal transit time (OCTT) was determined by lactulose challenge test given at 150 min, with concomitant breath hydrogen (H2) and gastrointestinal symptom determination. RESULTS: Cortisol increased substantially pre- to postexercise on NIGHT (+182%) versus DAY (+4%) (trial-time, P = 0.046), with no epinephrine (+41%) and norepinephrine (+102%) trial differences. I-FABP, but not claudin-3, increased pre- to postexercise on both trials (mean = 2269 pg·mL-1, 95% confidence interval = 1351-3187, +143%) (main effect of time [MEOT], P < 0.001). sCD14 increased pre- to postexercise (trial-time, P = 0.045, +5.6%) and was greater on DAY, but LBP decreased (MEOT, P = 0.019, -11.2%) on both trials. No trial difference was observed for systemic cytokine profile (MEOT, P = 0.004). Breath H2 responses (P = 0.019) showed that OCTT was significantly delayed on NIGHT (>84 min, with n = 3 showing no breath H2 turning point by 180 min postexercise) compared with DAY (mean = 54 min, 95% confidence interval = 29-79). NIGHT resulted in greater total gastrointestinal symptoms (P = 0.009) compared with DAY. No difference in feeding tolerance markers was observed between trials. CONCLUSION: Nocturnal exercise instigates greater gastrointestinal functional perturbations and symptoms compared with diurnal exercise. However, there are no circadian differences to gastrointestinal integrity and systemic perturbations in response to the same exertional stress and controlled procedures.


Subject(s)
Gastrointestinal Tract/physiology , Lipopolysaccharide Receptors/blood , Physical Exertion/physiology , Running/physiology , Acute-Phase Proteins , Adult , Carrier Proteins/blood , Catecholamines/blood , Claudin-3/blood , Epinephrine/blood , Fatty Acid-Binding Proteins/blood , Female , Gastrointestinal Diseases/blood , Gastrointestinal Diseases/etiology , Gastrointestinal Transit/physiology , Hot Temperature , Humans , Hydrocortisone/blood , Inflammation Mediators/blood , Male , Membrane Glycoproteins/blood , Norepinephrine/blood , Oxygen Consumption , Physical Endurance/physiology , Time Factors
19.
Clin Biochem ; 87: 67-73, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33096053

ABSTRACT

OBJECTIVE: To verify a rapid and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the quantification of catecholamines and their metabolites, and to validate its efficiency for the diagnosis of phaeochromocytomas and paragangliomas (PPGLs). METHODS: Plasma samples were pretreated with solid-phase extraction, followed by a 3-min UPLC-MS/MS analysis to quantify epinephrine (E), norepinephrine (NE), dopamine (DA), metanephrine (MN), normetanephrine (NMN) and 3-methoxytyramine (3-MT), simultaneously. The UPLC-MS/MS method was comprehensively verified and its diagnostic efficiency on PPGLs was tested using 7 PPGLs and 408 non-PPGLs patient plasma samples. RESULTS: Using the developed method, the limit of detections (LODs) of the 6 analytes ranged from 0.0002 nmol/L (MN) to 0.0250 nmol/L (NE), while the lower limit of measuring intervals (LLMIs) ranged from 0.05 nmol/L (E, MN and NMN) to 0.10 nmol/L (NE and DA). The reportable ranges were 0.05-30.00 nmol/L for E, MN and NMN, 0.10-30.00 nmol/L for NE and DA, 1.00-300.00 pg/mL for 3-MT. No significant matrix effect was detected after correcting using internal standard. Besides, intra-day and inter-day precision were also within acceptance criteria with coefficient of variations (CVs) ≤ 15% and recoveries ranged from 95% to 115% for all the 6 analytes. The carryover effect was lower than 10%. Its diagnostic efficiency for PPGLs was significantly increased, the areas under the receiver operating characteristic (ROC) curves were increased from 68.7% to 89.1% (using E, NE and DA) to 75.2%-99.9% (using MN, NMN and 3-MT). CONCLUSION: This study verified a rapid UPLC-MS/MS method for the determination of catecholamines and their metabolites in human plasma. It showed high diagnostic efficiency and will serve as an important tool to avoid the risk for missing patients with PPGLs.


Subject(s)
Catecholamines/blood , Chromatography, Liquid/methods , Paraganglioma/diagnosis , Pheochromocytoma/diagnosis , Tandem Mass Spectrometry/methods , Adrenal Gland Neoplasms/blood , Adrenal Gland Neoplasms/diagnosis , Calibration , Dopamine/analogs & derivatives , Dopamine/metabolism , Female , Humans , Limit of Detection , Male , Metanephrine/metabolism , Norepinephrine/blood , Normetanephrine/metabolism , Paraganglioma/blood , Pheochromocytoma/blood , ROC Curve
20.
J Cell Mol Med ; 25(2): 1314-1318, 2021 01.
Article in English | MEDLINE | ID: mdl-33300293

ABSTRACT

The aim of this study is to evaluate whether the alterations in glucose metabolism and insulin resistance are mechanisms presented in cardiac remodelling induced by the toxicity of cigarette smoke. Male Wistar rats were assigned to the control group (C; n = 12) and the cigarette smoke-exposed group (exposed to cigarette smoke over 2 months) (CS; n = 12). Transthoracic echocardiography, blood pressure assessment, serum biochemical analyses for catecholamines and cotinine, energy metabolism enzymes activities assay; HOMA index (homeostatic model assessment); immunohistochemistry; and Western blot for proteins involved in energy metabolism were performed. The CS group presented concentric hypertrophy, systolic and diastolic dysfunction, and higher oxidative stress. It was observed changes in energy metabolism, characterized by a higher HOMA index, lower concentration of GLUT4 (glucose transporter 4) and lower 3-hydroxyl-CoA dehydrogenase activity, suggesting the presence of insulin resistance. Yet, the cardiac glycogen was depleted, phosphofructokinase (PFK) and lactate dehydrogenase (LDH) increased, with normal pyruvate dehydrogenase (PDH) activity. The activity of citrate synthase, mitochondrial complexes and ATP synthase (adenosine triphosphate synthase) decreased and the expression of Sirtuin 1 (SIRT1) increased. In conclusion, exposure to cigarette smoke induces cardiac remodelling and dysfunction. The mitochondrial dysfunction and heart damage induced by cigarette smoke exposure are associated with insulin resistance and glucose metabolism changes.


Subject(s)
Glucose/metabolism , Insulin Resistance , Smoking/adverse effects , Ventricular Remodeling , Animals , Catecholamines/blood , Cotinine/blood , Electrocardiography , Energy Metabolism , Male , Oxidative Stress , Rats, Wistar
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