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The purpose of this study was to determine the effect of exercise intensity on the proportion and rate of carbohydrate oxidation and glucoregulatory hormone responses during recovery from exercise. Six physically active participants completed 1 hr of low-intensity (LI; 50% lactate threshold) or moderate-intensity (MI; 100% lactate threshold) exercise on separate days following a randomized counterbalanced design. During exercise and for 6 hr of recovery, samples of expired air were collected to determine oxygen consumption, respiratory exchange ratio, energy expenditure, and substrate oxidation rates. Blood samples were also collected to measure glucoregulatory hormones (catecholamines, GH) and metabolites (glucose, free fatty acids, lactate, pH, and bicarbonate). During exercise, respiratory exchange ratio, energy expenditure, and the proportion and rate of carbohydrate (CHO) oxidation were higher during MI compared with LI. However, during recovery from MI, respiratory exchange ratio and the proportion and rate of CHO oxidation were lower than preexercise levels and corresponding LI. During exercise and early recovery, catecholamines and growth hormone were higher in MI than LI, and there was a trend for higher levels of free fatty acids in the early recovery from MI compared with LI. In summary, CHO oxidation during exercise increases with exercise intensity but there is a preference for CHO sparing (and fat oxidation) during recovery from MI exercise compared with LI exercise. This exercise intensity-dependent shift in substrate oxidation during recovery is explained, in part, by the pattern of change of key glucoregulatory hormones including catecholamines and growth hormone and plasma fatty acid concentrations. [ABSTRACT FROM AUTHOR]

Background/Objectives: The 28-day mortality rate for septic shock is high, necessitating rapid and effective empiric antimicrobial therapy. In this study, we investigate whether the rate of catecholamine dose reduction in septic shock can indicate bacterial susceptibility to initial antimicrobial therapy or not. Methods: This retrospective observational study involved 108 adult patients with bacteraemia and septic shock admitted to the intensive care unit of Nihon University Itabashi Hospital between January 2017 and December 2023. They were classified into the Susceptible or Resistant groups based on the bacteria's susceptibility to the initial empiric antimicrobial therapy. Catecholamine dosages were converted to norepinephrine equivalent (NEE) scores, with the time course from the peak to the end of administration measured at NEE reductions. Results: Of the 108 patients, 94 were in the Susceptible group and 14 in the Resistant group. The Susceptible group showed faster reductions in catecholamine doses: the time to reduce the dose from the maximum NEE to 25% was 19 vs. 49.5 h (p = 0.0057), and to 0%, it was 29 vs. 54 h (p = 0.0475). The time to reduce the dose from the maximum NEE to 75% was 8 vs. 12.5 h (p = 0.0733), and to 50% it was 13 vs. 21.5 h (p = 0.1081). Conclusions: In septic shock with bacteraemia, a faster catecholamine dose reduction indicates bacterial susceptibility to the initial empiric antibiotics. This reduction rate can serve as an early clinical indicator of the appropriate initial empiric therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Chemosaturation for inoperable liver tumors can improve survival but often causes circulatory problems during filtration, making management challenging. In a study of 66 cases from 2016 to 2024, two approaches were compared: group 1 used one type of vasoactive drug (norepinephrine) and colloids, while group 2 used two types of vasoactive drugs (norepinephrine, vasopressin) and balanced crystalloids instead of colloids. Group 2 showed higher heart rates and lower blood pressure during filtration, with a higher dose of vasoactive drugs. Group 1 had higher lactate levels and used more blood products, while group 2 showed lower platelet counts. Both approaches showed no peri-interventional mortality. High-dose vasoactive drug use including vasopressin and balanced crystalloids is sufficient to stabilize circulatory function during chemosaturation. Background: Hepatic chemosaturation for inoperable liver tumors is a palliative treatment option with a beneficial effect on survival. However, the procedure regularly leads to circulatory failure during the filtration phase, and hemodynamic management is challenging. Our study aimed to compare two different strategies for hemodynamic management during chemosaturation to develop hypotheses for improving patient care and reducing peri-interventional morbidity. Methods: We conducted a single-center retrospective cohort study including 66 procedures of chemosaturation between May 2016 and March 2024. Procedures were divided into two groups: group 1 was managed with norepinephrine as the only vasopressor and liberal use of hydroxyethyl starch (HES). Group 2 was managed with norepinephrine and vasopressin and the preferred use of balanced crystalloids. We compared these two groups with respect to hemodynamic parameters, laboratory values, and post-interventional complications. Results: The heart rate was highest and the mean arterial pressure (MAP) was lowest during the filtration phase in both groups (p = 0.868, p = 0.270). The vasoactive inotropic score (VIS) was significantly higher in group 2 during the filtration phase (31.5 vs. 89, p < 0.001). Group 1 received significantly more HES overall (1000 mL vs. 0 mL, p < 0.001). Lactate levels at admission to the ICU were higher in group 1 (22.9 vs. 14.45 mg/dL, p = 0.041). Platelet counts were lower in group 2 from directly after chemosaturation through day 2 (p = 0.022, p = 0.001, p = 0.032). The INR differed significantly directly after chemosaturation (1.13 vs. 1.26, p = 0.015). Overall, group 1 received significantly more blood products peri-interventionally. There were two bleedings and one ischemic stroke in the overall cohort. There was no peri-interventional mortality. Conclusions: Advanced hemodynamic management ensures low peri-interventional mortality and morbidity. High-dose vasopressors, including vasopressin and the preferred use of balanced crystalloids, are sufficient to stabilize circulatory function during chemosaturation. [ABSTRACT FROM AUTHOR]

Intraoperative hypotension is a common perioperative complication in pediatric anesthesia. Oscillometric blood pressure measurement is therefore an essential part of standard perioperative monitoring in pediatric anesthesia. The optimum measurement site is the upper arm. Attention must be paid to the correct cuff size. Blood pressure should be measured before induction. In children undergoing major surgery or in critically ill children, invasive blood pressure measurement is still the gold standard. Continuous noninvasive measurement methods could be an alternative in the future. Threshold values to define hypotension remain unknown, even in awake children. There are also little data on hypotension thresholds in the perioperative setting. The most reliable measurement parameter for estimating hypotension is the mean arterial pressure. The threshold values for intraoperative hypotension are 40 mm Hg in newborns, 45 mm Hg in infants, 50 mm Hg in young children and 65 mm Hg in adolescents. Treatment should be initiated at a deviation of 10% and intensified at a deviation of 20%. Bolus administration of isotonic balanced crystalloid solutions, vasopressors and/or catecholamines are used as treatment options. Consistent and rapid intervention in the event of hypotension appears to be crucial. So far there is no evidence as to whether this leads to an improvement in outcome parameters. [ABSTRACT FROM AUTHOR]

Aims: Dopamine beta‐hydroxylase (DβH) inhibitors, like zamicastat, hold promise for treating pulmonary arterial hypertension. This study aimed to validate the mechanism of action of zamicastat by studying its effect on the overdrive of the sympathetic nervous system (SNS). Methods: A single‐centre, prospective, double‐blind, randomized, placebo‐controlled, crossover study evaluated the effect of 400 mg zamicastat in 22 healthy male subjects. Cold pressor test (CPT) was performed at screening and each treatment period on Days −1 and 10. Plasma and 24 h‐urine levels of dopamine (DA), epinephrine (EPI) and norepinephrine (NE), and plasma DβH activity, were measured. Results: Compared to placebo, zamicastat showed a − 4.62 mmHg decrease in systolic blood pressure during the cold stimulus vs. rest phases on Day 10 of CPT (P =.020). Zamicastat decreased mean arterial pressure response to cold stimulus during CPT (−2.62 mmHg; P =.025). At Day 10, zamicastat significantly increased plasma DA, before CPT (12.63 ng/L; P =.040) and after CPT (19.22 ng/L; P =.001) as well as the estimated plasma EPI change from baseline after CPT (P =.040). Inhibition of plasma DβH activity ranged from 19.8% to 25.0%. At Day 10, significant reductions in 24‐h urinary excretion of EPI (P =.002) and NE (P =.001) were observed. Zamicastat Cτ geometric mean ± GSD ranged from 45.86 ± 1.46 ng/mL on Day 3 to 58.64 ± 1.52 ng/mL on Day 10, with moderate inter‐individual variability (CV: 32.6%–36.6%). Steady state was already achieved on Day 6. Conclusions: Our results demonstrated the effect of zamicastat on the overdrive sympathetic response to cold stimulus, confirming its potential as SNS modulator. [ABSTRACT FROM AUTHOR]

Background: Studying biomarkers in children with temporomandibular disorders (TMD) such as epinephrine, norepinephrine, and dopamine may reveal factors like screen time or sleep loss that affect these biomarkers and predict TMD‐related pain, offering new research opportunities. Aim: To determine the association between stress and catecholamines with myofascial pain and headache related to TMD in children. Design: Sixty‐six 9‐ to 11‐year‐old children assisting at the clinics of Pediatric Dentistry of Universidad CES participated in the study. Myofascial pain and headache attributed to TMD were determined according to the Diagnostic Criteria for TMD (DC/TMD) Axis I. Stress was evaluated with the Perceived Stress Scale—Children (PSS‐C), and a 24‐h urine sample was analyzed using liquid chromatography to assay catecholamines. Single and multiple regression analyses were performed. Results: Children with a mean age of 10.3 years participated in the study. The mean score of stress was 29 ± 4. Perceived stress, dopamine, epinephrine, and norepinephrine were statistically significant predictors of myofascial pain and headache attributed to TMD in the single‐ and multiple variable logistic regression analyses. Conclusion: Stressful states and its biological biomarkers increase the probability of developing myofascial pain and headache attributed to TMD in children. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusion Pheochromocytoma is a unique tumour with a variety of clinical presentations. Coined as ‘the great masquerader’, it can present with the classical triad of headache, sweating and tachycardia and sometimes in an acute hypertensive crisis. This paper describes the evolutionary history of the diagnosis of this condition.A literature review was conducted using Medline Database from 1900 to 2023 outlining the methods of diagnosis for pheochromocytoma.There have been diagnostic dilemmas and localization challenges of pheochromocytoma over the last century. From the first description of pheochromocytoma in 1886 to the first successful resection in 1926, there was poor recognition of its atypical symptoms and lack of reliable diagnostic tests. Over the next few decades, there were significant advances in screening and biochemical tests. Further understanding of catecholamine release and metabolic pathways led to the development of tests to identify end products of catecholamine metabolism in plasma and urine. Computed imaging however heralded significant improvement in surgical planning and management. The evolution of histopathological diagnosis with the use of immunostains and genetic testing has further contributed to the identification of malignant pheochromocytomas and an understanding of their behaviours.Significant advances in the biochemical and imaging have shaped our understanding of pathophysiology and management. These diagnostic advances have enabled early and accurate detection and localization of pheochromocytomas to enable prompt surgical management. [ABSTRACT FROM AUTHOR]

Cerebellum is a key-structure for the modulation of motor, cognitive, social and affective functions, contributing to automatic behaviours through interactions with the cerebral cortex, basal ganglia and spinal cord. The predictive mechanisms used by the cerebellum cover not only sensorimotor functions but also reward-related tasks. Cerebellar circuits appear to encode temporal difference error and reward prediction error. From a chemical standpoint, cerebellar catecholamines modulate the rate of cerebellar-based cognitive learning, and mediate cerebellar contributions during complex behaviours. Reward processing and its associated emotions are tuned by the cerebellum which operates as a controller of adaptive homeostatic processes based on interoceptive and exteroceptive inputs. Lobules VI-VII/areas of the vermis are candidate regions for the cortico-subcortical signaling pathways associated with loss aversion and reward sensitivity, together with other nodes of the limbic circuitry. There is growing evidence that the cerebellum works as a hub of regional dysconnectivity across all mood states and that mental disorders involve the cerebellar circuitry, including mood and addiction disorders, and impaired eating behaviors where the cerebellum might be involved in longer time scales of prediction as compared to motor operations. Cerebellar patients exhibit aberrant social behaviour, showing aberrant impulsivity/compulsivity. The cerebellum is a master-piece of reward mechanisms, together with the striatum, ventral tegmental area (VTA) and prefrontal cortex (PFC). Critically, studies on reward processing reinforce our view that a fundamental role of the cerebellum is to construct internal models, perform predictions on the impact of future behaviour and compare what is predicted and what actually occurs. [ABSTRACT FROM AUTHOR]

The complement system is critically involved in the pathogenesis of sepsis. In particular, complement anaphylatoxin C5a is generated in excess during sepsis, leading to cellular dysfunction. Recent studies have shown that excessive C5a impairs adrenomedullary catecholamine production release and induces apoptosis in adrenomedullary cells. Currently, the mechanisms by which C5a impacts adrenal cell function are poorly understood. The PC12 cell model was used to examine the cellular effects following treatment with recombinant rat C5a. The levels of caspase activation and cell death, protein kinase signaling pathway activation, and changes in inflammatory protein expression were examined following treatment with C5a. There was an increase in apoptosis of PC12 cells following treatment with high-dose C5a. Ten inflammatory proteins, primarily involved in apoptosis, cell survival, and cell proliferation, were upregulated following treatment with high-dose C5a. Five inflammatory proteins, involved primarily in chemotaxis and anti-inflammatory functions, were downregulated. The ERK/MAPK, p38/MAPK, JNK/MAPK, and AKT protein kinase signaling pathways were upregulated in a C5aR-dependent manner. These results demonstrate an apoptotic effect and cellular signaling effect of high-dose C5a. Taken together, the overall data suggest that high levels of C5a may play a role in C5aR-dependent apoptosis of adrenal medullary cells in sepsis. [ABSTRACT FROM AUTHOR]

Methamphetamine (METH) is a drug of abuse, which induces behavioral sensitization following repeated doses. Since METH alters blood pressure, in the present study we assessed whether systolic and diastolic blood pressure (SBP and DBP, respectively) are sensitized as well. In this context, we investigated whether alterations develop within A1/C1 neurons in the vasomotor center. C57Bl/6J male mice were administered METH (5 mg/kg, daily for 5 consecutive days). Blood pressure was measured by tail-cuff plethysmography. We found a sensitized response both to SBP and DBP, along with a significant decrease of catecholamine neurons within A1/C1 (both in the rostral and caudal ventrolateral medulla), while no changes were detected in glutamic acid decarboxylase. The decrease of catecholamine neurons was neither associated with the appearance of degeneration-related marker Fluoro-Jade B nor with altered expression of α-synuclein. Rather, it was associated with reduced free radicals and phospho-cJun and increased heat shock protein-70 and p62/sequestosome within A1/C1 cells. Blood pressure sensitization was not associated with altered arterial reactivity. These data indicate that reiterated METH administration may increase blood pressure persistently and may predispose to an increased cardiovascular response to METH. These data may be relevant to explain cardiovascular events following METH administration and stressful conditions. [ABSTRACT FROM AUTHOR]

Introduction: Pheochromocytomas and paragangliomas (PPGLs) typically secrete catecholamines and their metabolites (metanephrines [MN] and normetanephrine [NMN]). Catecholamines are synthesized by several enzymes: phenylalanine hydroxylase (encoded by PAH), tyrosine hydroxylase (TH), aromatic L‐amino acid decarboxylase (DDC), dopamine β‐hydroxylase (DBH), and phenylethanolamine N‐methyltransferase (PNMT). MN/NMN secretion varies between anatomical and molecular subgroups. The aim of this study was to assess the correlation between DNA methylation of catecholamine synthesis genes and MN/NMN secretion. Methods: Gene promoter methylation of PAH, TH, AADC, DBH, and PNMT were extracted and calculated based on publicly available data. Comparisons and correlation analysis were performed between MN ± NMN (MN/NMN), NMN only, and neither/unknown secretion patterns. Methylation levels and MN/NMN patterns were compared by three genetic alteration subgroups: pseudohypoxia (PH), kinase signaling (KS), and others. Results: A total of 178 cases were included. Methylation of PAH CpGs negatively correlated with probability for MN/NMN secretion (p <.05 for all CpGs) and positively with NMN‐only secretion. NMN‐only secreting tumors had significantly higher promoter methylation of PAH, DBH, and PNMT compared with MN/NMN‐secreting tumors. MN/NMN‐secreting PPGLs had mainly KS alterations (52.1%), whereas NMN‐only PPGLs had PH alterations (41.9%). PPGLs in the PH versus KS group had gene promoter hypermethylation of PAH (p =.002), DBH (p =.02), and PNMT (p =.003). Conclusions: Promoter methylation of genes encoding catecholamine synthesis enzymes is strongly and inversely correlated with MN/NMN patterns in PPGLs. KS and PH‐related tumors have distinct methylation patterns. These results imply that methylation is a key regulatory mechanism of catecholamine synthesis in PPGLs. This study aimed to assess a possible association between the genetic background of pheochromocytoma/paraganglioma (PPGL) and gene regulation of catecholamine synthesis enzymes. We found that kinase signaling‐related and pseudohypoxia‐related alterations have distinct methylation patterns, implying methylation as a key regulatory mechanism of catecholamine synthesis in PPGLs. [ABSTRACT FROM AUTHOR]

Purpose: Pheochromocytoma is a rare neuroendocrine tumor. Despite the low incidence, these tumors are of indisputable importance. This study aimed to analyze the management of pheochromocytoma in a referral center, with an emphasis on the minimally invasive adrenalectomy, which is the preferred therapeutic approach. Methods: A retrospective analysis was performed on a cohort of patients diagnosed with pheochromocytoma who underwent adrenalectomy between January 2013 and December 2022. Clinical data including demographics, timelines, symptomatology, comorbidities, biochemical markers, genetic testing, surgical details, and follow-up outcomes, were collected and analyzed. Results: The cohort included 44 patients, predominantly women (52.27%), with a median age of 53.39 years (range 13–83). Most of patients exhibited paroxysmal symptoms suggesting catecholamine excess. Documented hypertension was the most frequent (86.36%), along with glucose anomalies (40.01%) and anxiety disorder (31.82%). Genetic testing was performed in 36 (81.81%) patients and 14 (38.88%) revealed a positive result, predominantly RET pathogenic variant. Laparoscopic surgery was performed in 34 (79.07%) patients, showing significantly shorter operative time (2.5 h vs. 4.25 h, t-test p < 0,001) and fewer complications (23.53% vs 77.78%, p = 0.008). Postoperative complications occurred in 36.36% of the patients, mostly mild (grade I, 56.25%), with no mortality. SDHB pathogenic variant correlated with both recurrent and metastatic disease (p = 0.006). One-year follow-up reported 9.09% recurrence and 6.82% metastasis. Conclusions: Adrenalectomy demonstrated a high safety and effectiveness. This study exhibited a higher rate of genetic testing referral than other studies. Despite past advances, there is still a need for further studies to establish protocols and evaluate new techniques. [ABSTRACT FROM AUTHOR]

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Responses occurring during intervals of operant tasks have been subdivided as interim, facultative, and terminal, depending on the time between response onset and reward. Although interval responses, also known as adjunctive responses, have been described in pigeons, rats, mice, monkeys, and humans, most experiments have been conducted in rats. We review the neurochemical basis of interval responses and examine the hypothesis that these responses modulate operant performance. Preliminary experiments indicate the involvement of biogenic amines, acetylcholine, and GABA during interval responding associated with operant tasks. In particular, catecholaminergic deafferentation of the basal ganglia modulated interval responses as did the peripheral injection of catecholamine reuptake blockers. Under the influence of amphetamine, interval responding may either increase or decrease, so that a wide range of responses must be selected to gauge drug effects. In non-drugged pigeons and rats, the expression of interval responses facilitates operant training. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and fibromyalgia (FM) are comorbid disorders with overlapping symptoms. Research highlights autonomic dysfunction compared to healthy individuals, particularly involving the sympathetic branch. While past reviews focused on neurophysiological assessments, this systematic review summarises biological adrenergic markers, offering deeper insights into the observed sympathetic dysfunction in ME/CFS and FM aiming to identify targetable pathophysiological mechanisms.A systematic search was performed on PubMed, Web of Science, Embase and Scopus. Studies investigating peripheral biological markers of adrenergic function in patients with ME/CFS or FM compared to healthy controls at baseline were included. Meta‐analyses were performed using R statistical software.This meta‐analysis of 37 studies, encompassing 543 ME/CFS patients and 651 FM patients, compared with 747 and 447 healthy controls, respectively, revealed elevated adrenaline (SMD = .49 [.31–.67]; Z = 5.29, p < .01) and β1 adrenergic receptor expression (SMD = .79 [.06–1.52]; Z = 2.13; p = .03) in blood of ME/CFS patients at rest. Additionally, patients with ME/CFS had a greater increase in the expression of α2A adrenergic receptor (AR, SMD = .57 [.18–.97]; Z = 2.85, p < .01), β2 AR (SMD = .41 [.02–.81]; Z = 2.04; p = .04) and COMT (SMD = .42 [.03–.81]; Z = 2.11; p = .03) after exercise and an increased response of noradrenaline to an orthostatic test (SMD = .11 [−.47 to −.70]; Z = 2.10; p = .04), both found in blood. FM patients showed no significant differences at baseline but exhibited a diminished adrenaline response to exercise (SMD = −.79 [−1.27 to −.30]; Z = −3.14; p < .01).This systematic review and meta‐analysis revealed adrenergic dysfunction mainly in patients with ME/CFS. Higher baseline adrenaline levels and atypical responses to exercise in ME/CFS indicate that sympathetic dysfunction, underscored by adrenergic abnormalities, is more involved in the pathophysiology of ME/CFS rather than FM. [ABSTRACT FROM AUTHOR]

Hypertensive crises in pediatric patients are rare conditions. However, determining their precise prevalence is more challenging than in adults due to the heterogeneity in the definition itself. These crises frequently occur without a prior diagnosis of hypertension and may indicate an underlying cause of secondary hypertension, including pheochromocytoma/paraganglioma (PPGL). The mechanisms of hypertensive crises in the pediatric population with PPGL are directly related to different types of catecholamine excess. Noradrenergic tumors typically present with sustained hypertension due to their predominant action on a1-adrenoceptors in the vasculature. Conversely, adrenergic tumors, through epinephrine binding to b2-adrenoceptors in addition to stimulation of a1- and a2-adrenoceptors, more frequently cause paroxysmal hypertension. Furthermore, the biochemical phenotype also reflects the tumor localization and the presence of a genetic mutation. Recent evidence suggests that more than 80% of PPGL in pediatric cases have a hereditary background. PPGL susceptibility mutations are categorized into three clusters; mutations in cluster 1 are more frequently associated with a noradrenergic phenotype, whereas those in cluster 2 are associated with an adrenergic phenotype. Consequently, the treatment of hypertensive crises in pediatric patients with PPGL, reflecting the underlying pathophysiology, requires first-line therapy with alpha-blockers, potentially in combination with beta-blockers only in the case of tachyarrhythmia after adequate alpha-blockade. The route of administration for treatment depends on the context, such as intraoperative or pre-surgical settings, and whether it presents as a hypertensive emergency (elevated blood pressure with acute target organ damage), where intravenous administration of antihypertensive drugs is mandatory. Conversely, in cases of hypertensive urgency, if children can tolerate oral therapy, intravenous administration may initially be avoided. However, managing these cases is complex and requires careful consideration of the selection and timing of therapy administration, particularly in pediatric patients. Therefore, facing these conditions in tertiary care centers through interdisciplinary collaboration is advisable to optimize therapeutic outcomes. [ABSTRACT FROM AUTHOR]

Objective To explore the role of catecholamine and its intermediate metabolites in the development of neurogenic pulmonary edema in the intensive care unit (ICU). Methods Clinical data were collected from 32 patients diagnosed with neurogenic pulmonary edema in the ICU between January 2020 and December 2023, forming the study group. Another 32 ICU patients from the same period who did not develop neurogenic pulmonary edema were selected as the control group. A retrospective analysis was conducted on the clinical data of both groups, comparing differences in blood gas indices, hemodynamic parameters, relevant laboratory indicators, inflammatory factors, and levels of cate-cholamines and their intermediate metabolites. Results Compared to the control group, the study group showed significant increases in partial pressure of carbon dioxide in arterial blood (PaCO2), fraction of inspiration O2(FiO2), artery alveolar oxygen partial pressure gradient (AaDO2), respiratory rate (RR), pulmonary artery wedge pressure (PAWP), interleukin-6 (IL-6), tumor necrosis factor (TNF-α), total catecholamines, epinephrine, metanephrine, normetanephrine, and norepinephrine, while partial pressure of oxygen in arterial blood (PaO2), arterial oxygen saturation (SaO2), arterial/alreolar oxygen tension ratio (a/APO2), PaO2/FiO2, and interferony (IFN - γ) were significantly decreased (P<0.05). No significant difference was observed in central venous pressure (CVP) levels between the groups (P>0.05). Correlation analysis indicated that epinephrine, norepinephrine, metanephrine, total catecholamines, and normetanephrine were positively correlated with PaCO2, FiO2, and AaDO2, and negatively correlated with PaO2, SaO2, a/APO2, and PaO2/FiO2(P<0.05). Conclusion Catecholamines and their intermediate metabolites are signifi- cantly elevated in ICU patients with neurogenic pulmonary edema and are correlated with blood gas indices, playing an important role in the occurrence and progression of the disease. [ABSTRACT FROM AUTHOR]

Background/Aim: Preeclampsia, a significant cause of maternal morbidity and mortality, is linked to increased cardiovascular risks. Catestatin regulates cardiovascular function which indicates its usefulness in understanding pathophysiology of preeclampsia and its severity. Aim of this study was to evaluate association of catestatin in preeclamptic women and control non preeclamptic women and assess its association with presence and severity of preeclampsia. Methods: A case-control study at Al-Zahraa Teaching Hospital, Iraq, performed from January to December 2023 involved 90 pregnant women: 30 with severe preeclampsia, 30 with mild preeclampsia and 30 healthy controls. Inclusion criteria were preeclamptic pregnant women at 27-40 weeks of gestation and age ranging from 20-40 years and similar non-eclamptic controls. Exclusions were smokers, chronic drug users and those with chronic illnesses. Data collection included general and clinical information, BMI, vital signs, examinations and laboratory tests including serum catestatin. Results: Catestatin levels varied significantly among severe preeclampsia, mild preeclampsia and control groups. Average catestatin level in severe preeclampsia group was markedly lower at 29.01 ng/mL, compared to 43.67 ng/mL in mild preeclampsia and 59.96 ng/mL in controls. The diagnostic performance of catestatin for severe preeclampsia was notable, with a cutoff point of ≤ 37.165 ng/mL, sensitivity of 80 % and specificity of 83.3 %, highlighting its potential as a critical biomarker in preeclampsia evaluation. Conclusion: Catestatin level was significantly lower in sever preeclampsia compared to mild and control group, which may indicate its association with preeclampsia. Lower catestatin in sever preeclampsia suggest its inverse relation with preeclampsia severity. [ABSTRACT FROM AUTHOR]

Background: Catecholamine-induced cardiomyopathy is an uncommon complication of pheochromocytoma. Pheochromocytoma is a rare tumor that predominantly occurs in adults, making catecholamine-induced cardiomyopathy secondary to pheochromocytoma in children an exceedingly rare presentation. Treatment typically consists of medical management followed by surgical resection. Mechanical support, typically salvage therapy with extracorporeal membrane oxygenation, has been used in adult patients with cardiogenic shock and after cardiac arrest, but to our knowledge, the use of mechanical support has not been described in pediatric patients. Case Report: A 16-year-old female presented with cardiogenic shock resulting from catecholamine-induced cardiomyopathy secondary to pheochromocytoma. She was treated with a percutaneous left ventricular assist device to allow myocardial recovery while medical therapy was optimized. Given the early initiation, the patient's myocardial recovery was prompt, and only 3 days of device support were required. She was discharged in good condition and subsequently underwent uncomplicated laparoscopic resection of the tumor a few weeks later. Conclusion: In pediatric patients with catecholamine-induced cardiomyopathy secondary to pheochromocytoma, aggressive measures of support--including mechanical support and infrequently used options such as percutaneous left ventricular assist devices--should be considered early in treatment to maintain adequate cardiac output, avoid cardiac arrest, and allow for prompt myocardial recovery. [ABSTRACT FROM AUTHOR]

Dynamins are large GTPases whose primary function is not only to catalyze membrane scission during endocytosis but also to modulate other cellular processes, such as actin polymerization and vesicle trafficking. Recently, we reported that centronuclear myopathy associated dynamin‐2 mutations, p.A618T, and p.S619L, impair Ca2+‐induced exocytosis of the glucose transporter GLUT4 containing vesicles in immortalized human myoblasts. As exocytosis and endocytosis occur within rapid timescales, here we applied high‐temporal resolution techniques, such as patch‐clamp capacitance measurements and carbon‐fiber amperometry to assess the effects of these mutations on these two cellular processes, using bovine chromaffin cells as a study model. We found that the expression of any of these dynamin‐2 mutants inhibits a dynamin and F‐actin‐dependent form of fast endocytosis triggered by single action potential stimulus, as well as inhibits a slow compensatory endocytosis induced by 500 ms square depolarization. Both dynamin‐2 mutants further reduced the exocytosis induced by 500 ms depolarizations, and the frequency of release events and the recruitment of neuropeptide Y (NPY)‐labeled vesicles to the cell cortex after stimulation of nicotinic acetylcholine receptors with 1,1‐dimethyl‐4‐phenyl piperazine iodide (DMPP). They also provoked a significant decrease in the Ca2+‐induced formation of new actin filaments in permeabilized chromaffin cells. In summary, our results indicate that the centronuclear myopathy (CNM)‐linked p.A618T and p.S619L mutations in dynamin‐2 affect exocytosis and endocytosis, being the disruption of F‐actin dynamics a possible explanation for these results. These impaired cellular processes might underlie the pathogenic mechanisms associated with these mutations. [ABSTRACT FROM AUTHOR]

The sympathoadrenal system plays an essential role in forming the body's response to the action of stimuli of various natures and intensities. The content of deposited catecholamines in peripheral blood erythrocytes is one of the most accessible parameters for an adequate description of the functional activity of the sympathoadrenal system in humans and rats. The aim of the work is to assess the accumulation of catecholamines in erythrocytes of sea ruffs Scorpaena porcus L. at various pollution levels in the bays of Sevastopol. The phenomenon of accumulation of catecholamines in erythrocytes of the peripheral blood of fish is revealed. The concentration of erythrocytes with deposited catecholamines was higher in fish from polluted bays. In 2006, fish from Alexander Bay exhibited a significantly higher erythrocyte content of deposited catecholamines (36.04%) compared to those from the background area (28.19%) and Quarantine Bay (30.74%) (P < 0.01). Similar levels were observed between Quarantine Bay and the coast of Balaklava. In 2007, fish from Alexander Bay maintained a high erythrocyte catecholamine content (35.2%), while those from Quarantine Bay exhibited a lower level (23.8%) (P ≤ 0.01). In 2008, the erythrocyte catecholamine content in Quarantine Bay was six times higher than that observed in fish from Martynov Bay. These findings underscore the variability in catecholamine concentrations among fish populations inhabiting different coastal regions, suggesting potential environmental influences on stress responses.. [ABSTRACT FROM AUTHOR]

The article discusses the California poppy (Eschscholzia californica), a prominent wildflower in western North America recognized for its vibrant flowers and significant role in Indigenous healing traditions, as well as its status as the state flower of California. Topics include its cultural significance among Native Americans, its medicinal uses and cultivation, and its historical introduction to Europe and the connection to California's identity. 4o mini.

Catecholamine-induced cardiomyopathy (CCM) is an entity associated with increased levels of catecholamines causing subendocardial and papillary muscle cardiomyocyte degeneration and necrosis. In 2020, 49 autopsies from early rabbit deaths in a colony used for medical device biocompatibility studies were submitted for microscopic examination. Of the 49 rabbits, 26 had histologic changes consistent with CCM. No common stressor for CCM was determined in affected rabbits. Animals were generally male, were 12–16-wk-old, and were found dead or had bloating, lethargy, and/or diarrhea. Those observed with clinical signs were euthanized and autopsied per the organization's standard operating procedures. Heart lesions consisted of various degrees of apical subendocardial myocardial degeneration and necrosis. Common non-cardiac lesions included pulmonary congestion and edema, hepatic congestion and centrilobular hepatocellular degeneration, and/or variable intestinal submucosal edema. [ABSTRACT FROM AUTHOR]

Background Phaeochromocytoma multisystem crisis (PMC) is characterized by labile blood pressures (extremes of hypo- and/or hypertension) and multiorgan failure as a result of catecholamine excess. Initial stabilization requires pharmacological and/or mechanical circulatory support, followed by the institution of antihypertensives to correct the underlying pathophysiology. Case summary A previously well 40-year-old male developed a sudden onset of breathlessness. On presentation, he was in shock with multiorgan failure. He required intubation, mechanical ventilation, dual inotropic support, and renal replacement therapy. Bedside echocardiogram showed a severely impaired left ventricular ejection fraction (LVEF) of 25%. Coronary angiography revealed normal coronary arteries. In view of raised inflammatory markers and transaminitis, a computed tomography abdomen/pelvis was performed. An incidental left adrenal mass was found. Further work-ups revealed raised plasma metanephrine and normetanephrine, 24-h urine epinephrine, and norepinephrine. A cardiac magnetic resonance (CMR) showed myocardial inflammation and reverse Takotsubo pattern of regional wall motion abnormality (RWMA). The diagnosis of cardiogenic shock and stress cardiomyopathy secondary to PMC was made. He was subsequently initiated on α- and β-blockers and goal-directed medical therapy for heart failure. A 68Ga-DOTATATE scan showed avid tracer uptake of the left phaeochromocytoma. An interval CMR 3 weeks from presentation showed near normalization of the LVEF and RWMA. He underwent a successful laparoscopic left adrenalectomy and was antihypertensive-free since. Discussion The clinical suspicion for PMC as the cause of cardiogenic shock requires astute clinical judgement, while the management requires an understanding of the underlying pathophysiology that calls for multidisciplinary inputs. [ABSTRACT FROM AUTHOR]

Paragangliomas are rare extra-adrenal neuroendocrine tumors originating from chromaffin tissue that present a diagnostic and therapeutic challenge due to their diverse clinical manifestations and low incidence. While these tumors often manifest as catecholamine-secreting functional tumors, their clinical presentation can vary, leading to delayed diagnosis and challenging management. This study presents the case of a 22-year-old patient with cardiac paraganglioma who initially presented with angina-like symptoms, highlighting the importance of considering this rare condition in young individuals with nonspecific complaints. Diagnostic imaging, including transthoracic echocardiography, CT angiography, and MRI, played a crucial role in identifying the tumor's location and vascularization. Surgical excision, including pulmonary artery graft and CABG, was the primary management approach, which was accompanied by intraoperative complications that later led to CCU admission, followed by postoperative complications, ultimately leading to the patient's death. This case highlights the significance of early recognition and management of complications following a surgical approach to treat paragangliomas. [ABSTRACT FROM AUTHOR]

Abstract The objective of this investigation was to assess the impact of elevated catecholamine concentrations, induced through cold-water hand immersion, on the oxygen consumption (V̇O2) kinetics during intense exercise, and to contrast this effect with that of the priming effect. Ten active participants underwent three 8-minute constant work rate exercises (CWR) at ∆25%, with one CWR preceded by hand cooling (2 min at 0 °C, HC) and two consecutive CWR to induced priming effect on the second bout (SB). Pulmonary gas exchange and blood samples were analyzed to measure levels of epinephrine (E) and norepinephrine (NE). Results demonstrated a significant increase in the primary phase amplitude of V̇O2 kinetics in response to both hand HC (33.9 mL.min−1.kg−1; CI [32.2;35.7], p

IntroductionCatecholamine vasopressors such as norepinephrine are the standard drugs used to maintain mean arterial pressure during liver transplantation. At high doses, catecholamines may impair organ perfusion. Angiotensin II is a peptide vasoconstrictor that may improve renal perfusion pressure and glomerular filtration rate, a haemodynamic profile that could reduce acute kidney injury. Angiotensin II is approved for vasodilatory shock but has not been rigorously evaluated for treatment of hypotension during liver transplantation. The objective is to assess the efficacy of angiotensin II as a second-line vasopressor infusion during liver transplantation. This trial will establish the efficacy of angiotensin II in decreasing the dose of norepinephrine to maintain adequate blood pressure. Completion of this study will allow design of a follow-up, multicentre trial powered to detect a reduction of organ injury in liver transplantation.Methods and analysisThis is a double-blind, randomised clinical trial. Eligible subjects are adults with a Model for End-Stage Liver Disease Sodium Score ≥25 undergoing deceased donor liver transplantation. Subjects are randomised 1:1 to receive angiotensin II or saline placebo as the second-line vasopressor infusion. The study drug infusion is initiated on reaching a norepinephrine dose of 0.05 µg kg-1 min-1 and titrated per protocol. The primary outcome is the dose of norepinephrine required to maintain a mean arterial pressure ≥65 mm Hg. Secondary outcomes include vasopressin or epinephrine requirement and duration of hypotension. Safety outcomes include incidence of thromboembolism within 48 hours of the end of surgery and severe hypertension. An intention-to-treat analysis will be performed for all randomised subjects receiving the study drug. The total dose of norepinephrine will be compared between the two arms by a one-tailed Mann-Whitney U test.Ethics and disseminationThe trial protocol was approved by the local Institutional Review Board (#20-30948). Results will be posted on ClinicalTrials.gov and published in a peer-reviewed journal.Trial registration numberClinicalTrials.govNCT04901169.

In obesity, CD11c+ innate immune cells are recruited to adipose tissue and create an inflammatory state that causes both insulin and catecholamine resistance. We found that ablation of Gnas, the gene that encodes Gαs, in CD11c expressing cells protects mice from obesity, glucose intolerance, and insulin resistance. Transplantation studies showed that the lean phenotype was conferred by bone marrow-derived cells and did not require adaptive immunity. Loss of cAMP signaling was associated with increased adipose tissue norepinephrine and cAMP signaling, and prevention of catecholamine resistance. The adipose tissue had reduced expression of catecholamine transport and degradation enzymes, suggesting that the elevated norepinephrine resulted from decreased catabolism. Collectively, our results identified an important role for cAMP signaling in CD11c+ innate immune cells in whole-body metabolism by controlling norepinephrine levels in white adipose tissue, modulating catecholamine-induced lipolysis and increasing thermogenesis, which, together, created a lean phenotype.Article highlightsWe undertook this study to understand how immune cells communicate with adipocytes, specifically, whether cAMP signaling in the immune cell and the adipocyte are connected. We identified a reciprocal interaction between CD11c+ innate immune cells and adipocytes in which high cAMP signaling in the immune cell compartment induces low cAMP signaling in adipocytes and vice versa. This interaction regulates lipolysis in adipocytes and inflammation in immune cells, resulting in either a lean, obesity-resistant, and insulin-sensitive phenotype, or an obese, insulin-resistant phenotype.

Purpose: to develop a model of the early stage of retinal neurodegeneration via an intravitreal injection of the dopaminergic neurotoxin. Material and methods. The experiment was carried out on 20 Chinchilla rabbits. The experimental groups received intravitreal injection of 0.1 ml of 6-hydroxydopamine (6-OHDA) in NaCl 0.9 % with 0.5 % ascorbate, containing 0.25 or 0.5 mg 6-OHDA. The control group received injections of 0.1 ml of NaCl-ascorbate solution without neurotoxin. On the 7th and the 14th days after the injection, intraocular pressure (IOP), pupillary light reaction and ocular blood flow were estimated and the fundus was examined. On the 7th day after an injection of 0.25 mg 6-OHDA, we used ELISA to measure dopamine concentration in retinal homogenates, while on the 14th day after an injection of 0.5 mg 6-OHDA, the concentrations of dopamine, norepinephrine, TNF-a and endothelin-1 were measured by the same method. Results. On the 7th day after a 0,25 mg injection of neurotoxine, we revealed a decrease of dopamine in the retina (0.043 ± 0.130 pg/mg protein compared with 0.10 ± 0,03 pg/mg protein in the controls, р < 0.01). On the 14th day, dopamine and norepinephrine levels showed a fourfold increase (р < 0.05). An injection of 0.5 mg of 6-OHDA caused a threefold increase of dopamine (р < 0.05) and a fivefold increase of norepinephrine (р < 0.01) concentration in comparison with the controls. On the 14th day, endotheline-1 level was 65 % higher than in the controls after a 0.25 mg 6-OHDA injection (р < 0.01) and 45 % higher after a 0,5 mg injection (р

Background: Due to the high prevalence of hypertension in patients with autosomal dominant polycystic kidney disease (ADPKD) and advanced chronic kidney disease, diagnosing secondary hypertension poses challenges. We present a rare case of pheochromocytoma in an ADPKD patient to highlight the diagnostic difficulties in identifying secondary hypertension due to pheochromocytoma/paraganglioma (PPGL) in end-stage renal disease (ESRD) patients. Case Report: A 48-year-old female with ADPKD and ESRD experienced recurrent hypertensive crises (up to 220/135 mmHg) accompanied by palpitations and tremors that recurred over the past 2 years. Introduction of a betablocker to the antihypertensive therapy aggravated her symptoms. The initial documentation of elevated urinary metanephrines was interpreted as false positive finding due to renal failure. Subsequent measurements of free plasma metanephrines revealed significant elevations raising suspicion of PPGL. Magnetic resonance imaging identified a 29 mm right adrenal mass. The patient underwent right adrenalectomy resulting in resolution of the hypertensive crises. Discussion: The diagnosis of PPGLs can present significant challenges and is further complicated in ESRD due to nonspecific clinical symptoms and diagnostic pitfalls. Less than 20 PPGL cases have been reported in patients with ESRD. The intolerance of beta-blocker therapy, as well as the use of a scoring system for the likelihood of PPGL should have raised suspicion. Conclusion: PPGL should be considered in all patients with uncontrolled hypertension and beta-blockers intolerance, even in the presence of other etiologic mechanisms such as ESRD. Measuring free plasma metanephrines provides the most reliable biochemical screening in the context of impaired renal function.

The aim of this study was to explore the impact of anesthetic drugs currently used to perform lower digestive endoscopy on serum concentrations of inflammation markers and catecholamines. We selected 120 patients and divided them into three lots of 40 patients each: L1, in which no anesthetics were used; L2, in which propofol was used; and L3, in which propofol combined with fentanyl was used. All patients had serum concentrations of adrenaline/epinephrine (EPI), noradrenaline/norepinephrine (NE), tumor necrosis factor alpha (TNF-α), interleukin-4 (IL-4), IL-6, IL-8, and IL-10, taken at three time points: at the beginning of the endoscopic procedure (T0), 15 min after (T1), and 2 h after the end of the endoscopic procedure (T2). The results of the research showed changes in the levels of catecholamines and interleukins (ILs) at T0, with an increased response in L1 above the mean recorded in L2 and L3 (p < 0.001). At T1, increased values were recorded in all lots; values were significantly higher in L1. At T2, the values recorded in L3 were significantly lower than the values in L2 (student T, p < 0.001) and L1, in which the level of these markers continued to increase, reaching double values compared to T0 (student T, p < 0.001). In L2 at T1, the dose of propofol correlated much better with NE, EPI, and well-known cytokines. Our results show that propofol combined with fentanyl can significantly inhibit the activation of systemic immune and neuroendocrine response during painless lower digestive endoscopy.

Abstract Aims Takotsubo syndrome (TTS) is an acute heart failure (AHF) syndrome mimicking the symptoms of acute myocardial infarction. Impaired outcome has been shown, making risk stratification and novel therapeutic concepts a necessity. We hypothesized insulin resistance with elevated plasma glucose and potentially myocardial glucose deprivation to contribute to the pathogenesis of TTS and investigated the therapeutic benefit of insulin in vivo. Methods and results First, we retrospectively analysed patient data of n = 265 TTS cases (85.7% female, mean age 71.1 ± 14.1 years) with documented initial plasma glucose from the Department of Cardiology of the University Hospital Heidelberg in Germany (May 2011 to May 2021). Median split of the study population according to glucose levels (≤123 mg/dL vs. >123 mg/dL) yielded significantly elevated mean heart rate (80.75 ± 18.96 vs. 90.01 ± 22.19 b.p.m., P

Introduction: Smoking elevates catecholamines that increase the risk for cardiovascular disease. Sparse evidence exists about the effects of e-cigarettes and catecholamines. Higher levels of catecholamines could trigger the increased heart rate, blood pressure, and decreased vascular function reported with the use of e-cigarettes. We investigated the difference in urinary catecholamines and their metabolites before and after the use of an e-cigarette containing nicotine or cigarettes compared to no tobacco use. Methods: In our observational cohort exposure study, healthy adults aged 21– 45 years who were currently using e-cigarettes, cigarettes, or had never used tobacco, participated in an acute exposure visit using their most common tobacco product. Urine was collected before, 1, and 2 hours after a 3-second puff every 30 seconds for 10 minutes on an e-cigarette or straw or use of 1 cigarette. Urinary catecholamines and their metabolites were measured by ultra-high-performance liquid chromatography. Participants (n=323) were grouped by the product used at the visit. We compared levels of creatinine normalized log-transformed urinary catecholamines and their metabolites across groups using Dunn's test following a Kruskal-Wallis test in unadjusted and demographically adjusted models. Results: Prior to use, individuals who used cigarettes (n=70) had lower urinary metabolites from epinephrine, serotonin, and norepinephrine. No differences were seen in those who used e-cigarettes (n=171) and those who did not use tobacco (n=82). In fully adjusted models, 1 h after the use of a combustible or e-cigarette, log-transformed urinary metabolites from norepinephrine (β=1.22; 95% CI: 0.39– 2.05, p=0.004 and β=1.06; 95% CI: 0.39–1.74, p=0.002), dopamine (β=0.37; 95% CI: 0.24–0.5, p<0.001 and β=0.15; 95% CI: 0.05–0.26, p<0.001), and epinephrine (β=1.89; 95% CI: 0.51–3.27, p=0.008 and β=1.49; 95% CI: 0.38–2.61, p=0.009) were elevated. In fully adjusted models, combustible cigarette use was associated with elevated urinary norepinephrine (β=0.46; 95% CI: 0.13–0.81, p=0.007) and dopamine (β=0.19; 95% CI: 0.06–0.31, p=0.003) 1 h after use. Conclusions: We found that the use of both e-cigarettes and cigarettes was associated with elevated urinary catecholamines or their metabolites. Catecholamines could be useful as a biomarker of harm for tobacco use and considered by tobacco regulatory scientists in future research. [ABSTRACT FROM AUTHOR]

Psychological stress is associated with numerous deleterious health effects. Accumulating evidence suggests acute exercise reduces stress reactivity. As stressors activate a wide array of psychological and physiological systems it is imperative stress responses are examined through a multidimensional lens. Moreover, it seems prudent to consider whether stress responses are influenced by exercise intervention characteristics such as modality, duration, intensity, timing, as well as participant fitness/physical activity levels. The current review therefore examined the role of acute exercise on stress reactivity through a multidimensional approach, as well as whether exercise intervention characteristics and participant fitness/physical activity levels may moderate these effects. Stress reactivity was assessed via heart rate, blood pressure, cortisol, catecholamines, and self-report. A systematic search following PRISMA guidelines of five databases was updated in November 2022. Reviewed studies met the following criteria: English language, participants aged ≥ 18, use of acute exercise, use of a validated stress-inducing task, and assessment(s) of stress reactivity. Thirty-one studies (1386 participants) were included. Acute exercise resulted in reliable reductions to blood pressure and cortisol. Acute exercise yielded mostly negligible effects on heart rate reactivity and negligible effects on self-report measures. As for exercise intervention characteristics, intensity-dependent effects were present, such that higher intensities yielded larger reductions to reactivity measures, while limited evidence was present for duration, modality, and timing-dependent effects. Regarding participant fitness/physical activity levels, the effects on stress reactivity were mixed. Future work should standardize the definitions and assessment time points of stress reactivity, as well as investigate the interaction between physiological and psychological stress responses in real-world contexts. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a second most common neurodegenerative disorder characterized by the selective and progressive degeneration of dopaminergic neurons in substantia nigra pars compacta. Rotenone is a neurotoxin which selectively degenerate dopaminergic neurons in striatum, leading to cause PD like symptoms. Rotenone was administered at a dose of 1.5 mg/kg, i.p. from day 1 to day 40. Treatment with doxycycline (50 and 100 mg/kg, p.o), tocopherol (5 mg and 10 mg/kg, p.o) alone, doxycycline (50 mg/kg, p.o) in combination with tocopherol (10 mg/kg, p.o), and ropinirole (0.5 mg/kg, i.p.) was given for 40 days 1 h prior to administration of rotenone. All behavioral parameters were analyzed on weekly basis. On day 41, animals were sacrificed and the striatum region was isolated for neurotransmitters estimation (dopamine, serotonin, norepinephrine, GABA and glutamate), biochemical analysis (GSH, nitrite, LPO, mitochondrial complexes I and IV), inflammatory markers estimation (IL-6, IL-1β and TNF-α) and activity of MAO-A, MAO-B. Doxycycline and tocopherol in combination significantly attenuated behavioral, neurotransmitters and biochemical alterations induced by rotenone in experimental rats as compared to alone treatment with DOX and TOCO. Similarly, DOX and TOCO combination significantly reduced the level of inflammatory markers, prevented the biochemical changes, decreased MAO-A and MAO-B and improved complex-I, complex-IV, cAMP levels significantly. The current study revealed that a combination of doxycycline with tocopherol contributed to the prevention of PD like symptoms in rats by antioxidant, anti-inflammatory, MAO inhibitory and neuromodulatory mechanisms. [ABSTRACT FROM AUTHOR]

(1) Background: Physical activity may cause an imbalance in the major functions of the human body. This study aimed to investigate the effects of endurance running training on the parameters of the antioxidant defense system (SOD, CAT, GPx, GR, GSH), LPO (malondialdehyde, MDA), and stress hormones (A, NA) in young healthy, previously untrained men. (2) Methods: The training program was as follows: 8 weeks of running, three times per week; the duration of a single session was 30–70 min, the intensity was twice a week in the so-called extensive endurance zone, and once a week in the anaerobic threshold zone. Blood samples were collected from the subjects, before and after the running program. (3) Results: The training program resulted in a significant increase in maximal oxygen consumption (p < 0.001). The activities of SOD, GPx, and GR also increased significantly (p < 0.05, p < 0.01, and p < 0.05, respectively), while CAT activity and GSH and MDA concentrations remained unchanged. The concentration of A decreased (p < 0.05), while the NA concentration increased significantly (p < 0.05). SOD, GPx, GR, and NA positively correlated with VO2max (p < 0.05, p < 0.001, p < 0.01, p < 0.05, respectively), while a negative correlation was detected between A and VO2max (p < 0.05). (4) Conclusions: These results indicate that there is no persistent oxidative stress in response to the applied 8-week running program, probably due to exercise-induced protective alterations in the antioxidant defense system. Furthermore, adaptations occurred at the hormonal level, making the organism more ready for a new challenge. [ABSTRACT FROM AUTHOR]

Hyperthermia is known as a hyperadrenergic state, yet there is a lack of data on the sympathetic responses to ambient heat stress in humans. Therefore, we investigated the plasma epinephrine and norepinephrine concentrations of healthy young and older adults exposed to 3 h of very hot and dry, as well as hot and humid, heat, both with accompanying activities of daily living. We hypothesized that older adults, compared with young adults, would have augmented increases in epinephrine and norepinephrine concentrations secondary to increased thermal strain. Young (n = 20) and older (n = 18) participants underwent two 3-h heat exposures on different days: very hot and dry [47°C and 15% relative humidity (RH)] and hot and humid (41°C and 40% RH). To mimic heat generation comparable to activities of daily living, participants performed seven 5-min bouts of light cycling (approximately 3 METS) dispersed throughout the heat exposure. We measured plasma concentrations of epinephrine and norepinephrine at baseline, end, and 2-h postheat exposure. There was a group-wide increase in epinephrine from baseline to the end of the heat exposure (Δ19 ± 27 pg/mL; P < 0.001) in the hot and humid condition, but not in the very hot and dry condition (Δ6 ± 19 pg/mL; P = 0.10). There were group-wide decreases in norepinephrine concentrations from baseline to the end of the heat exposure in both the very hot and dry (Δ-131 ± 169 pg/mL; P < 0.001) and the hot and humid (Δ-138 ± 157 pg/mL; P < 0.001) conditions, with both returning to near baseline at 2-h postexposure. These data suggest that ambient heating with accompanying bouts of light intermittent exercise may lead to decreases in circulating concentrations of norepinephrine. NEW & NOTEWORTHY: Herein we present plasma epinephrine and norepinephrine concentrations to 3 h of very hot and dry, as well as hot and humid, heat exposures with accompanying activities of daily living in young and older participants. We found 1) increased plasma concentrations of epinephrine in young and older adults following the hot and humid, but not the very hot and dry exposures and 2) decreased concentrations of norepinephrine in both groups following exposure to both conditions. [ABSTRACT FROM AUTHOR]

While the dopaminergic system is important for cognitive processes, it is also sensitive to the influence of physical activity (PA). We summarize current evidence on whether PA-related changes in the human dopaminergic system are associated with alterations in cognitive performance, discuss recent advances, and highlight challenges and opportunities for future research. [ABSTRACT FROM AUTHOR]

High voltage‐gated Ca2+ channels (HVCCs) shape the electrical activity and control hormone release in most endocrine cells. HVCCs are multi‐subunit protein complexes formed by the pore‐forming α1 and the auxiliary β, α2δ and γ subunits. Four genes code for the α2δ isoforms. At the mRNA level, mouse chromaffin cells (MCCs) express predominantly the CACNA2D1 gene coding for the α2δ‐1 isoform. Here we show that α2δ‐1 deletion led to ∼60% reduced HVCC Ca2+ influx with slower inactivation kinetics. Pharmacological dissection showed that HVCC composition remained similar in α2δ‐1−/− MCCs compared to wild‐type (WT), demonstrating that α2δ‐1 exerts similar functional effects on all HVCC isoforms. Consistent with reduced HVCC Ca2+ influx, α2δ‐1−/− MCCs showed reduced spontaneous electrical activity with action potentials (APs) having a shorter half‐maximal duration caused by faster rising and decay slopes. However, the induced electrical activity showed opposite effects with α2δ‐1−/− MCCs displaying significantly higher AP frequency in the tonic firing mode as well as an increase in the number of cells firing AP bursts compared to WT. This gain‐of‐function phenotype was caused by reduced functional activation of Ca2+‐dependent K+ currents. Additionally, despite the reduced HVCC Ca2+ influx, the intracellular Ca2+ transients and vesicle exocytosis or endocytosis were unaltered in α2δ‐1−/− MCCs compared to WT during sustained stimulation. In conclusion, our study shows that α2δ‐1 genetic deletion reduces Ca2+ influx in cultured MCCs but leads to a paradoxical increase in catecholamine secretion due to increased excitability. Key points: Deletion of the α2δ‐1 high voltage‐gated Ca2+ channel (HVCC) subunit reduces mouse chromaffin cell (MCC) Ca2+ influx by ∼60% but causes a paradoxical increase in induced excitability.MCC intracellular Ca2+ transients are unaffected by the reduced HVCC Ca2+ influx.Deletion of α2δ‐1 reduces the immediately releasable pool vesicle exocytosis but has no effect on catecholamine (CA) release in response to sustained stimuli.The increased electrical activity and CA release from MCCs might contribute to the previously reported cardiovascular phenotype of patients carrying α2δ‐1 loss‐of‐function mutations. [ABSTRACT FROM AUTHOR]

Expanding on earlier observations, we show that many melanin materials, in vitro synthesized from a wide range of precursors, can be fractionated into a dark-colored precipitate and a near-colorless, dispersible fraction. The dispersible fractions exhibited absorbance in the UVA and UVB range of the electromagnetic spectrum, but none in the visible range. In addition, fluorescent properties were associated with all dispersible fractions obtained. FT-IR spectroscopic analyses were performed to compare both types of fractions. Overall, it appears that some of the properties associated with melanin (UV absorbance, fluorescence) may not necessarily reside in the dark-colored portion of melanin, but in a colorless fraction of the material. It remains to be seen whether any of these in vitro observations have any relevance in vivo. However, we raise the possibility that the presence of a colorless fraction within melanin materials and their associated properties may have received inadequate attention. Given the important association between melanin, UV protection, and skin cancer, it is worthwhile to consider this additional aspect of melanin chemistry. [ABSTRACT FROM AUTHOR]

Numerous studies have suggested that noise exposure might be associated with changes in stress hormone levels. However, quantitative evidence for these effects in humans is rare and remains controversial. This study aimed to investigate the acute effects of exposure to noise and its different levels on stress hormone changes in task performance. Quasi-experimental noise exposure environment was established for 90 male university student volunteers in their twenties, and each was exposed to different noise levels during task performance. The stress hormones tested included cortisol, adrenocorticotropic hormone (ACTH), adrenaline, and noradrenaline. A one-way ANOVA was performed to investigate differences in hormone levels measured in the three groups according to the noise exposure levels (35, 45, or 75 dB). Analysis of covariance (ANCOVA) was used to adjust for confounding factors that might affect hormone levels. After adjusting for confounders, significant exposure-dependent differences were found in hormone levels in salivary cortisol, serum cortisol, serum ACTH, and serum adrenaline. The amount of hormonal increase in 75 dB exposure group compared to 35 or 45 dB groups was detected. Similar results were also seen in the rate of change analysis. Our findings indicate that short-term noise exposure during task performance elevates stress hormone levels. Further, the extent of stress hormone alterations varies with noise exposure levels. Changes in hormone levels are an objective measure that may be used to identify health effects and stress responses in various noise environments. [ABSTRACT FROM AUTHOR]

One element, potassium, can be identified as the connecting link in the research of Czech neurophysiologist Prof. František Vyskočil. It accompanied him from the first student experiments on the frog muscle (Solandt effect) via sodium-potassium pump and quantum and non-quantum release of neurotransmitters (e.g. acetylcholine) to the most appreciated work on the reversible leakage of K+ from brain neurons during the Leao´s spreading cortical depression, often preceding migraine. He used a wide range of methods at the systemic, cellular and genetic levels. The electrophysiology and biochemistry of nerve-muscle contacts and synapses in the muscles and brain led to a range of interesting findings and discoveries on normal, denervated and hibernating laboratory mammals and in tissue cultures. Among others, he co-discovered the facilitating effects of catecholamines (adrenaline in particular) by end-plate synchronization of individual evoked quanta. This helps to understand the general effectiveness of nerve-muscle performance during actual stress. After the transition of the Czech Republic to capitalism, together with Dr. Josef Zicha from our Institute, he was an avid promoter of scientometry as an objective system of estimating a scientist´s success in basic research (journal Vesmír, 69: 644-645, 1990 in Czech). [ABSTRACT FROM AUTHOR]

Background: "Metacontrol" describes the ability to maintain an optimal balance between cognitive control styles that are either more persistent or more flexible. Recent studies have shown a link between metacontrol and aperiodic EEG patterns. The present study aimed to gain more insight into the neurobiological underpinnings of metacontrol by using methylphenidate (MPH), a compound known to increase postsynaptic catecholamine levels and modulate cortical noise. Methods: In a double-blind, randomized, placebo-controlled study design, we investigated the effect of MPH (0.5 mg/kg) on aperiodic EEG activity during a flanker task in a sample of n = 25 neurotypical adults. To quantify cortical noise, we employed the fitting oscillations and one over f algorithm. Results: Compared with placebo, MPH increased the aperiodic exponent, suggesting that it reduces cortical noise in 2 ways. First, it did so in a state-like fashion, as the main effect of the drug was visible and significant in both pre-trial and within-trial periods. Second, the electrode-specific analyses showed that the drug also affects specific processes by dampening the downregulation of noise in conditions requiring more control. Conclusions: Our findings suggest that the aperiodic exponent provides a neural marker of metacontrol states and changes therein. Further, we propose that the effectiveness of medications targeting catecholaminergic signaling can be evaluated by studying changes of cortical noise, fostering the idea of using the quantification of cortical noise as an indicator in pharmacological treatment. [ABSTRACT FROM AUTHOR]

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Introduction: The purpose was to study the indicators of physical development of primary-school-aged children with intellectual disability by observing the type of autonomic nervous regulation and their levels of catecholamines and serotonin. Methods: A total of 168 primary school age children were examined, of which 54 had intellectual disability. The autonomic nervous system was assessed using cardiointervalography; anthropometric parameters were applied in accordance with recommendations. The contents of serotonin and catecholamines in blood plasma and lymphocytes were assessed using enzyme immunoassay and luminescent histochemical methods. Results and conclusions: Delayed physical and mental development in children with intellectual disability were associated with low serotonin levels in this group of children. The optimal option for the physical development of children with intellectual disability is a sympathetic type of autonomic nervous regulation, while negative-type vagotonic nervous regulation was associated with the maximum delay in physical development. The hypersympathetic type of nervous regulation was accompanied by minimal changes in physical development, despite the hormonal imbalance in the ratio of catecholamines and serotonin. The level of the neurotransmitter serotonin is a prognostic marker of the physical development of children of primary school age. The total amount of catecholamines and serotonin in blood plasma has a direct relationship with the amount of these neurotransmitters in blood lymphocytes; the more hormones in plasma, the more of them in lymphocytes. Therefore, the determination of the contents of catecholamines and serotonin in lymphocytes can be used as a model for studying neurotransmitters in humans. [ABSTRACT FROM AUTHOR]

Introduction: Digitalization in medicine is steadily increasing. Complex treatments, scarce personnel resources and a high level of documentation are a constant burden on healthcare systems. The balancing between correct manual documentation in the digital records and limited staff resources is rarely successful. The aim of this study is to evaluate the adherence between documentation and lack of documentation in the treatment of critical care patients. Material and Methods: For the evaluation, data from the hospital information system (HIS) of several intensive care units (ICU) were examined in conjunction with data collected from a checklist. All boluses of sedatives, analgesics and catecholamines were documented paper based across all shifts and all weekdays and compared with corresponding digital data from the HIS (2019–2022) of previous years. Results: 939 complete digital patient records revealed a massive under-documentation of the medication administration compared to that applied according to the checklist. Only 12% of all administered catecholamines, 11% of α2-agonists, 33% of propofol, 92% of midazolam and 46% of opioids were found in the digital recordings. In comparison, the effect was more pronounced on weekdays compared to weekends. In addition, the highest documentation gap was found in the comparison of early shifts. Comparing neurosurgical vs. internal vs. anesthesiologic ICUs there was a highly significant difference between anesthesiologic ICUs compared with other disciplines (p < 0.0001). Discussion: Our data shows that there is a remarkable documentation gap and incongruence in the area of applied boli. Automated documentation by connecting syringe pumps that enter data directly into the HIS can not only reduce the workload, but also lead to comprehensive and legally required documentation of all administered medication. [ABSTRACT FROM AUTHOR]

Background: Trauma and emergency surgery are major causes of morbidity and mortality. The objective of this study was to determine whether serum levels of epinephrine and norepinephrine are associated with aging and mortality. Methods: This was a prospective observational cohort study conducted in a surgical critical care unit. We included 90 patients who were admitted for postoperative care, because of major trauma, or both. We collected demographic and clinical variables, as well as serum levels of epinephrine and norepinephrine. Results: For patients in the > 60-year age group, the use of vasoactive drugs was found to be associated with an undetectable epinephrine level (OR [95% CI] = 6.36 [1.12, 36.08]), p = 0.05). For the patients with undetectable epinephrine levels, the in-hospital mortality was higher among those with a norepinephrine level ≥ 2006.5 pg/mL (OR [95% CI] = 4.00 [1.27, 12.58]), p = 0.03). Conclusions: There is an association between age and mortality. Undetectable serum epinephrine, which is more common in older patients, could contribute to poor outcomes. The use of epinephrine might improve the clinical prognosis in older surgical patients with shock. [ABSTRACT FROM AUTHOR]

Objective • This study seeks to assess the functional status and central fatigue state of athletes in the Shanghai women’s volleyball team during the training phase of the 2021 Shaanxi National Games. Employing a comprehensive methodology involving functional status assessment and catecholamine index analysis, the research aims to establish a scientific foundation for preparing for the 2025 National Games. Additionally, it aims to provide valuable insights for preventing excessive fatigue and promoting the rational elimination of fatigue. Methods • (1) Participants: Twelve adult female volleyball players from Shanghai participated in the study. The average age of the participants was 26.23±3.39 years, and they had an average training period of 11.92±3.73 years. (2) Training Period: The study spanned a duration of 21 consecutive weeks, during which the training regimen was divided into eight distinct stages based on specific content and tasks. (3) Testing Procedures: Various tests were conducted at specific intervals throughout the training period. These included assessments performed at the conclusion of each upper training stage and the Metamorphosis stage. Additionally, comprehensive testing was carried out before and after both the preliminaries and championship matches of the National Games. Fasting elbow venous blood samples were collected for assessing functional status indicators, including Hemoglobin (HGB), Blood Urea Nitrogen (BUN), Creatine Kinase (CK), Serum Ferritin (SF), Testosterone (T), Cortisol (C), Testosterone/Cortisol ratio (T/C). Moreover, blood catecholamine indicators (Dopamine (DA), Norepinephrine (NE), Epinephrine (E) were analyzed before the National Games, at the end of Metamorphosis stage 2, and at the conclusion of upper phase 3. (4)Data Analysis: The collected data underwent rigorous statistical processing using SPSS 25.0 statistical software package and Microsoft Excel software. This comprehensive analysis was essential for deriving meaningful conclusions and identifying significant patterns in the athletes’ functional status and central fatigue states. Results •(1) HGB, T, and T/C showed the same trend throughout the whole period. The upper phase 1 drops significantly to the lowest value and the Metamorphosis stage increases. The training stage 2 fell again, but the decline was less than the training stage 1, and the Metamorphosis stage 2 increased significantly, and there was a significant difference between the basic value and the training stages (P < .05). Testosterone increased significantly to the maximum before the final of the National Games, and there was a significant difference between the baseline and the prematch (P < .05). (2) At the end of the training stage, DA, and E decreased significantly, and there was no significant difference in NE decline. During the preliminaries of the National Games, DA, NE, and E all declined, but there was no significant difference. In the championship stage, DA, NE, and E both increased, but only NE was significantly different from the Metamorphosis stage and the championship (P < .05). Conclusion • (1) Performance Enhancement: Recognizing and addressing performance dips in the training stage through targeted adjustments can optimize athlete performance. Athletes exhibit improved competitiveness during actual games, indicating the effectiveness of tailored interventions (2) Strategic Fatigue Management: Distinguishing between body and central fatigue is vital. Monitoring sensitive markers like blood dopamine and adrenaline in the training stage enables timely fatigue management. Understanding the relationship between blood testosterone and dopamine offers insights into energy levels and mental resilience, aiding in effective training strategies. (3) Efficient Evaluation Tools: Hemoglobin and blood testosterone serve as efficient markers for evaluating athletes’ states. Regular assessment of these indicators allows for proactive adjustments in training, preventing excessive fatigue and promoting overall well-being. [ABSTRACT FROM AUTHOR]

Introduction: Prognosis and management of patients with intermediate-risk pulmonary embolism (PE) is challenging. We investigated whether stroke volume may be used to identify the subset of this population at increased risk of clinical deterioration or PE-related death. Our secondary objective was to compare echocardiographic measurements of patients who received escalated interventions vs anticoagulation monotherapy. Methods: We selected patients with intermediate-risk PE, who had comprehensive echocardiography within 18 hours of PE diagnosis and before any escalated interventions, from a PE registry populated by 11 emergency departments. Echocardiographers measured right ventricle (RV) size, tricuspid annular plane systolic excursion (TAPSE), and stroke volume (SV) using velocity time integral (VTI) by left ventricular (LV) outflow tract Doppler or two-dimensional method of discs (MOD). The primary outcome was a composite of PE-related death, cardiac arrest, catecholamine administration for sustained hypotension, or emergency respiratory intervention during the index hospitalization. Secondary outcome was escalated intervention with reperfusion or extracorporeal membrane oxygenation therapy. Results: Of 370 intermediate-risk PE patients (mean age 64.0 ± 15.5 years, 38.1% male), 39 (10.5%) had the primary outcome. These 39 patients had lower mean SV regardless of measurement method than those without the primary outcome: SV MOD 36.2 vs 49.9 milliliters (mL), P < 0.001; SV Doppler 41.7 vs 57.2 mL, P = 0.003; VTI 13.6 vs 17.9 centimeters [cm], P = 0.003. Patients with primary outcome also had lower mean TAPSE than those without (1.54 vs 1.81 cm, P = 0.003). Multivariable models, selecting SV as predictor, had area under the receiver operating curve of 0.8 and Brier score 0.08. The best echocardiographic predictor of our primary outcome was SV MOD (odds ratio 0.72 [0.53, 0.94], P = 0.02). Patients who received escalated interventions had significantly lower SV or surrogate measurements, greater RV dilatation, and lower RV systolic function than patients who received anticoagulation monotherapy. Low stroke volume was a predictor of clinical deterioration and PE-related death. Low SV may be used to identify a subset of intermediate-risk PE patients, who are higher risk (intermediate-high risk), and for whom escalated interventions should be considered. [ABSTRACT FROM AUTHOR]

Neuroblastoma is a common pediatric tumor arising from the post-ganglionic sympathetic nervous system and is associated with hypertension in 25% of cases. We describe an unusual case of labile, multi-drug resistant hypertension associated with chemotherapy administration for neuroblastoma and provide potential management strategies in this scenario. We report the case of a 4-year-old female with a history of headaches who presented with hypertensive emergency and evidence of end-organ damage, including posterior reversible encephalopathy syndrome, acute cerebral infarct, concentric left ventricular hypertrophy, and growth failure secondary to a large, abdominal catecholamine-secreting neuroblastoma, which compressed the kidney vasculature and inferior vena cava. She was classified as intermediate risk according to Children's Oncology Group criteria and underwent chemotherapy, complicated by labile hypertension, followed by surgical resection. Vigilance in monitoring and treatment of hypertension is recommended during chemotherapy for neuroblastoma due to the potential catecholamine release in the setting of tumor lysis. [ABSTRACT FROM AUTHOR]