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Paragangliomas are slow-growing, extra-adrenal neuroendocrine tumors with rare intracranial presentation. Although benign, they can be locally aggressive tumors causing bone destruction and compression related symptoms. We report the case of a 19 years old, normotensive female who presented with headache and vertigo for the past six months. Her examination showed right-sided conductive hearing loss and signs of cranial nerve X, vagus nerve palsy. Neuroimaging revealed a lobulated, extra-axial mass measuring 5.4 x 4.2 x 6.8 cm in right cerebellopontine angle (CPA). Subtotal surgical resection was achievable. Histopathology was suggestive of benign, non-secretory paraganglioma. The diagnosis of primary CPA was reached after ruling out other sources of paraganglioma in abdomen, pelvis and thorax. Radiotherapy was advised on follow up visit with no new post-operative deficits seen. Primary CPA paraganglioma should be included in the list of differentials of CPA lesions. Surgical excision in the absence of preoperative embolization of paraganglioma can be successful. [ABSTRACT FROM AUTHOR]

The measurement of selected norepinephrine metabolites, such as 3,4-dihydroxyphenylglycol (DHPG), 3-methoxy-4-hydroxyphenylethylenglycol (MHPG), and vanillylmandelic acid (VMA), in biological matrices—including urine—is of great clinical importance for the diagnosis and monitoring of diseases. This fact has forced researchers to evaluate new analytical methodologies for their isolation and preconcentration from biological samples. In this study, the three most popular extraction techniques—liquid-liquid extraction (LLE), solid-phase extraction (SPE), and a new 3D-printed system for dispersive solid-phase extraction (3D-DSPE)—were investigated. Micellar electrokinetic chromatography (MEKC) with a diode array detector (DAD) at 200 nm wavelength was applied to the separation of analytes, allowing for the assessment of the extraction efficiency (R) and enrichment factor (EF) for the tested extraction types. The separation buffer (BGE) consisted of 5 mM sodium tetraborate decahydrate, 50 mM SDS, 15% (v/v) MeOH, 150 mM boric acid, and 1 mM of 1-hexyl-3-methylimidazolium chloride (the apparent pH of the BGE equaled 7.3). The EF for each extraction procedure was calculated with respect to standard mixtures of the analytes at the same concentration levels. The 3D-DSPE procedure, using DVB sorbent and acetone as the desorption solvent, proved to be the most effective approach for the simultaneous extraction and determination of the chosen compounds, achieving over 3-fold signal amplification for DHPG and MHPG and over 2-fold for VMA. Moreover, all extraction protocols used for the selected norepinephrine metabolites were estimated and discussed. It was also confirmed that the 3D-DSPE-MEKC approach could be considered an effective tool for sample pretreatment and separation of chosen endogenous analytes in urine samples. [ABSTRACT FROM AUTHOR]

Physical activity highly impacts the neuroendocrine system and hormonal secretion. Numerous variables, both those related to the individual, including genetics, age, sex, biological rhythms, nutritional status, level of training, intake of drugs or supplements, and previous or current pathologies, and those related to the physical activity in terms of type, intensity, and duration of exercise, or environmental conditions can shape the hormonal response to physical exercise. The aim of this review is to provide an overview of the effects of physical exercise on hormonal levels in the human body, focusing on changes in concentrations of hormones such as cortisol, testosterone, and insulin in response to different types and intensities of physical activity. Regular monitoring of hormonal responses in athletes could be a potential tool to design individual training programs and prevent overtraining syndrome. [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]

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]

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]

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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.

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.

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]

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]

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]

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]

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]

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]

(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]

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]

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]

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]

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]

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]

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]

Biogenic amines are signaling molecules with multiple roles in the central nervous system and in peripheral organs, including the gonads. A series of studies indicated that these molecules, their biosynthetic enzymes and their receptors are present in the testis and that they are involved in the regulation of male reproductive physiology and/or pathology. This mini-review aims to summarize the current knowledge in this field and to pinpoint existing research gaps. We suggest that the widespread clinical use of pharmacological agonists/antagonists of these signaling molecules, calls for new investigations in this area. They are necessary to evaluate the relevance of biogenic amines for human male fertility and infertility, as well as the potential value of at least one of them as an anti-aging compound in the testis. [ABSTRACT FROM AUTHOR]

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.

Background Amphiregulin (AREG) is a growth factor linked to cardioprotection and heart pathology during myocardial stress. Our aim was to investigate cardiac AREG expression, its potential as a postmortem hypothermia marker and its possible stress hormone dependency in different types of deaths.Materials and methods Heart RNA was isolated from hypothermic, cardiac and non-cardiac deaths. Relative AREG mRNA levels and urine stress hormone concentrations were measured by qPCR and enzyme-linked immunosorbent assays from eight different death cause groups. Receiver operating characteristic curve was used to evaluate a cut-off point for AREG expression as a hypothermia marker. Regulatory elements were predicted by PROMO.Results The AREG mRNA levels were significantly higher in hypothermic deaths than in most cardiac and non-cardiac deaths. AREG expression indicated hypothermic deaths with nearly 70% sensitivity and specificity. However, high expression levels were also detected in non-ischaemic deaths. The highest concentrations of adrenaline and cortisol were detected in hypothermic deaths, while the highest noradrenaline concentrations associated with atherosclerotic heart disease (AHD) deaths with acute myocardial infarction and trauma deaths. There were no significant correlations between stress hormones and AREG mRNA in hypothermic and non-cardiac deaths, whereas moderate-to-high associations were detected in cardiac deaths. Putative response elements for cortisol and catecholamines were found in AREG.Conclusions Severe hypothermia activates cardiac AREG expression practicable as a postmortem hypothermia marker. Cortisol and catecholamines may act as transcriptional modifiers of this gene, especially in long-term ischaemic heart disease. However, the exact role of these hormones in upregulation of AREG during hypothermia remains unclear.

Background and aim: The important role of catecholamines has been gradually emphasized in the pathogenesis of neurodegenerative process. As the most prevalent form of cognitive dysfunction, Alzheimer's disease (AD) and vascular dementia (VaD) have the distinct pathological features and pathogenic mechanisms, however, the differential involvement of central and peripheral catecholamines between AD and VaD was still unclear. Methods: Triple-transgenic AD (3 × Tg-AD) mice and chronic cerebral hypoperfusion (CCH) in rats induced by two-vessel occlusion (2VO) were used as the AD and VaD model in this study, respectively. The concentrations of catecholamines (dopamine, epinephrine and norepinephrine) and their metabolites (3-methoxytyramine, metanephrine and normetanephrine) in serum and five brain regions (hippocampus, cortex, corpus striatum, thalamus and pons) from 3 × Tg-AD mice and 2VO rats were quantitatively determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay. Results: High expression and distribution of hippocampal dopamine, and epinephrine and norepinephrine in the cortex and thalamus were found in the early 3 × Tg-AD model, whereas chronic cerebral hypoperfusion induced by 2VO mainly affected the central noradrenergic and noradrenergic system, but not dopaminergic system. The increased serum levels of catecholamines were investigated in the 2VO rats, but not in the 3 × Tg-AD mice. Conclusion: The differential expression and distribution of central catecholamines and their metabolites suggests the distinct catecholamines-related pathogenesis between AD and VaD. Peripheral catecholamine surge may be involved in the development of VaD, and the treatment strategy to prevent or reverse the effects of peripheral catecholamines may be protective for VaD.

Anastomosing hemangioma (AH) is an exceedingly rare benign vascular tumor, often mistaken for malignant neoplasms due to its histological features. First described in 2009, AH has been documented in various sites, including the kidney, liver, and adrenal gland. This report presents a 64-year-old man who, following a bicycle accident, underwent imaging that revealed a nodule suspicious for a paraganglioma in the right para-caval region. Despite the high radiotracer uptake on 68Ga-DOTANOC PET scan, which suggested paraganglioma, the patient remained asymptomatic and laboratory tests ruled out excessive catecholamine secretion. Surgical excision led to a diagnosis of AH, distinguished by its unique anastomosing vascular pattern and histological similarity to angiosarcoma. This case underlines the diagnostic challenges and potential for overtreatment of AH, highlighting the need for heightened awareness and careful histopathological and imaging evaluation to avoid misdiagnosis and ensure appropriate management. [ABSTRACT FROM AUTHOR]

The emergence of new tools to image neurotransmitters, neuromodulators, and neuropeptides has transformed our understanding of the role of neurochemistry in brain development and cognition, yet analysis of this new dimension of neurobiological information remains challenging. Here, we image dopamine modulation in striatal brain tissue slices with near-infrared catecholamine nanosensors (nIRCat) and implement machine learning to determine which features of dopamine modulation are unique to changes in stimulation strength, and to different neuroanatomical regions. We trained a support vector machine and a random forest classifier to decide whether the recordings were made from the dorsolateral striatum (DLS) versus the dorsomedial striatum (DMS) and find that machine learning is able to accurately distinguish dopamine release that occurs in DLS from that occurring in DMS in a manner unachievable with canonical statistical analysis. Furthermore, our analysis determines that dopamine modulatory signals including the number of unique dopamine release sites and peak dopamine released per stimulation event are most predictive of neuroanatomy. This is in light of integrated neuromodulator amount being the conventional metric used to monitor neuromodulation in animal studies. Lastly, our study finds that machine learning discrimination of different stimulation strengths or neuroanatomical regions is only possible in adult animals, suggesting a high degree of variability in dopamine modulatory kinetics during animal development. Our study highlights that machine learning could become a broadly utilized tool to differentiate between neuroanatomical regions or between neurotypical and disease states, with features not detectable by conventional statistical analysis.

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

Background: Post-induction hypotension (PIH) often occurs during general anesthesia induction. This study aimed to investigate blood catecholamine levels during induction of general anesthesia in patients with PIH undergoing laparoscopic cholecystectomy. Methods: This prospective study included 557 adult patients who underwent laparoscopic cholecystectomy under general anesthesia. PIH was defined as a greater than 20% decrease in systolic blood pressure from the pre-induction value, a systolic arterial pressure of less than 90 mmHg, or both. Plasma concentrations of epinephrine and norepinephrine during the induction of general anesthesia were determined using enzyme-linked immunosorbent assay. Multivariate logistic regression analysis evaluated the association between the clinical factors and PIH. Results: Of the 557 patients, 390 had PIH, and the remaining 167 were allocated to the non-PIH group. Changes in blood adrenaline, noradrenaline levels, or both were more pronounced in the PIH than in the non-PIH group (p<0.05). Age, body mass index, a history of hypertension, preoperative systolic blood pressure, and propofol or sufentanil dose were independent predictors of PIH. Conclusion: The changes of blood catecholamines in patients with more stable hemodynamics during the induction of general anesthesia are smaller than that in patients with post-induction hypotension. Trial registration: ChiCTR2200055549, 12/01/2022. [ABSTRACT FROM AUTHOR]

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 FROM AUTHOR]

Background/Objectives: Catecholamines are among those agents that are indispensable in modern intensive care medicine. The rapid availability of hygienically impeccable and correctly concentrated injectable solutions, e.g., for syringe pumps, is becoming more and more important. However, little research has been conducted regarding how the use of catecholamines is distributed in different wards and what options can be used to achieve optimal availability. Methods: In a retrospective monocentric study from 2019 to 2022, all continuously applied catecholamines in intensive care units (ICU) and intermediate care units (IMC) were investigated. The focus was on potential optimization by utilizing manufactured ready-to-administer solutions in the context of the economization of patient care. Results: Norepinephrine syringes represented 81% of all syringes administered, appearing to be the most frequently used on all wards. Production by the in-house pharmacy showed both financial advantages and an increase in patient safety compared to syringes produced at the bedside. Discussion: Increasing numbers of critically ill patients coupled with growing staff shortages and an increased awareness of safety requirements are driving the move towards ready-to-use and ready-to-administer solutions in critical care medicine. In-house manufacturing by hospital pharmacies can be a promising option to optimize processes and improve the economics of patient care. Conclusions: Individual calculations of the required catecholamine preparations with regard to possible economic advantages should be carried out in hospitals. In particular, in-house production of ready-to-use and ready-to-administer preparations could significantly increase patient safety and seems to be economically viable. [ABSTRACT FROM AUTHOR]

Methamphetamine (METH) exposure increases locomotor sensitization. However, no study has explored the occurrence of cardiovascular sensitization. The present study, carried out in mice, analyzed the following: (i) METH sensitization extending to systolic blood pressure (SBP); (ii) a potential correlation between ambulatory and cardiovascular sensitization; and (iii) morphological alterations within meso-striatal, meso-limbic and pontine catecholamine systems including c-fos expression. Locomotor activity, SBP and occurrence of morphological alterations of catecholaminergic neurons were assessed in C57Bl/6J mice following daily i.p. injections of either saline or METH (1, 2 or 5 mg/kg) for 5 consecutive days and following 6 days of withdrawal. Reiterated exposure to the lower doses of METH (1 mg/kg and 2 mg/kg) produced in mice locomotor sensitization without altering SBP. In contrast, repeated treatment with the highest dose of METH (5 mg/kg) produced sensitization of SBP in the absence of locomotor sensitization. No morphological alterations but increases in c-fos expression within neurons of locus coeruleus and nucleus accumbens were detected. The present data suggest that METH produces plastic changes that extend beyond the motor systems to alter autonomic regulation. This cardiovascular sensitization occurs independently of locomotor sensitization. The persistency of increased blood pressure may underlie specific mechanisms operating in producing hypertension. [ABSTRACT FROM AUTHOR]

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 < 0.001), left ventricular end‐diastolic pressure (LVEDP, 18.51 ± 8.35 vs. 23.09 ± 7.97 mmHg, P < 0.001), C‐reactive protein (26.14 ± 43.30 vs. 46.4 ± 68.6 mg/L, P = 0.006), leukocyte count (10.12 ± 4.29 vs. 15.05 ± 9.83/nL, P < 0.001), peak high‐sensitive Troponin T (hs‐TnT, 515.44 ± 672.15 vs. 711.40 ± 736.37 pg/mL, P = 0.005), reduced left ventricular ejection fraction (EF, 34.92 ± 8.94 vs. 31.35 ± 8.06%, P < 0.001), and elevated intrahospital mortality (2.3% vs. 12.1%, P = 0.002) in the high‐glucose group (Student's t‐test, Mann–Whitney U test, or chi‐squared test). Linear regression indicated a significant association of glucose with HR (P < 0.001), LVEDP (P = 0.014), hs‐TnT kinetics from admission to the next day (P < 0.001), hs‐TnT the day after admission (P < 0.001), as well as peak hsTnT (P < 0.001). Logistic regression revealed significant association of glucose with a composite intrahospital outcome including catecholamine use, respiratory support, and resuscitation [OR 1.010 (1.004–1.015), P = 0.001]. To further investigate the potential role of glucose in TTS pathophysiology experimentally, we utilized an in vivo murine model of epinephrine (EPI)‐driven reversible AHF. For this, male mice underwent therapeutic injection of insulin (INS, 1 IU/kg) or/and glucose (GLU, 0.5 g/kg) after EPI (2.5 mg/kg), both of which markedly improved mean EF (EPI 34.3% vs. EPI + INS + GLU 43.7%, P = 0.025) and significantly blunted mean hs‐TnT (EPI 14 393 pg/mL vs. EPI + INS 6864 pg/mL at 24 h, P = 0.039). Particularly, insulin additionally ameliorated myocardial pro‐inflammatory gene expression, suggesting an anti‐inflammatory effect of acute insulin therapy. Conclusions: Elevated initial plasma glucose was associated with adverse outcome‐relevant parameters in TTS and may present a surrogate parameter of heightened catecholaminergic drive. In mice, insulin‐ and glucose injection both improved EPI‐induced AHF and myocardial damage, indicating insulin resistance rather than detrimental effects of hyperglycaemia itself as the underlying cause. Future studies will investigate the role of HbA1c as a risk stratifier and of insulin‐based therapy in TTS. [ABSTRACT FROM AUTHOR]

Misophonia is a neurophysiological disorder with behavioral implications, is complex and multifactorial in origin, and is characterized by an atypical and disproportionate emotional response to specific sounds or associated visual stimuli. Triggers include human-generated sounds, mainly sounds related to feeding and breathing processes, and repetitive mechanical sounds. In response to the triggering stimulus, the patient experiences immediate, high-intensity, disproportionate physical and emotional reactions that affect their quality of life and social functioning. The symptoms of misophonia can occur at any age, but onset in childhood or adolescence is most common. Affected children live in a constant state of anxiety, suffer continuous physical and emotional discomfort, and are thus exposed to significant chronic stress. Chronic stress, especially during childhood, has consequences on the main biological systems through the dysregulation of the hypothalamic–pituitary–adrenal axis, including the gastrointestinal tract. Here, we provide arguments for a positive correlation between misophonic pathology and gastrointestinal symptoms, and this hypothesis may be the starting point for further longitudinal studies that could investigate the correlations between these childhood vulnerabilities caused by misophonia and their effect on the gastrointestinal system. Further research to study this hypothesis is essential to ensure correct and timely diagnosis and optimal psychological and pharmacological support. [ABSTRACT FROM AUTHOR]

Background: Pheochromocytoma is a rare catecholamine-producing tumour originating from adrenal chromaffin cells. Classic clinical presentation includes headache, diaphoresis and palpitation. Syncope is uncommon and may result from hypotension or arrhythmia. We report a case of neurally mediated syncope in pheochromocytoma associated with cardiac repolarization abnormalities, a unique presentation of the disease. Case presentation: This case report presents a 28 year-old woman, describing recurrent syncope usually preceded by prodromes such as headache, visual blurring, heart palpitations and psychomotor agitation. Firstly she was diagnosed with anxiety and depression, but there was no improvement of symptoms with psychiatric treatment. Previous Holter revealed long QT interval. Echocardiogram showed normal dimensions, preserved left ventricular function and no valvopathies. The patient was referred for a Head-up tilt test (HUTT) in order to investigate reflex syncope. The electrocardiogram (ECG) exhibited normal sinus rhythm and diffuse cardiac repolarisation abnormalities. HUTT was positive for vasodepressor type neurally mediated syncope and ECG showed U waves after a syncope episode. This electrocardiographic finding motivated further clinical investigation. The patient also described abdominal pain, increased abdominal volume, weight loss and blood pressure instability. Based on clinical history and ventricular repolarisation abnormalities uncovered by HUTT, pheochromocytoma was suspected. Urinary test was positive for catecholamines and the abdominal imaging revelead expansive lesion. She underwent surgery to remove the pheochromocytoma, confirmed by immunohistochemistry. Conclusions: After surgery she had no recurrency of symptoms, remaining asymptomatic after six years of follow-up, suggesting a cause-effect relationship between neurally mediated syncope and pheochromocytoma. [ABSTRACT FROM AUTHOR]

Introduction: The present study evaluated the effect of preslaughter stress intensities on the behavioral, physiological, blood biochemicals, and hormonal responses in goats. Methods: Twenty-seven intact male goats (Ardi breed, 10 months of age, 27 kg liveweight) were divided into three treatment groups viz., the control (C) group, ear pulling (EP) group, and leg pulling (LP) group. Various behavioral, physiological, blood biochemical and hormonal responses were recorded before and after handling. Results and Discussion: The EP and LP goats had a higher frequency and intensity of vocalization as compared to control goats. The preslaughter handling stress intensities had a significant effect on the before and after handling values of heart rate, respiration rate, rectal temperature, and ear temperature. Further, among groups, the glucose value increased significantly upon preslaughter handling as compared to the baseline value. The LP goats had significantly higher after-handling value for lactate dehydrogenase (LDH) as compared to the before-handling value. The catecholamines (adrenaline and noradrenaline) and β-endorphin concentrations increased significantly upon preslaughter handling. The higher physiological, behavioral, blood biochemical, and hormonal response indicated higher preslaughter stress in EP and LP goats. Both levels of intensity revealed unfavorable responses in goats that may adversely affect animal welfare and meat quality. Thus, to ensure minimal adverse effects on behavior, physiology, blood enzymes, and hormonal responses, it is recommended to follow animal welfare principles when implementing preslaughter handling practices. [ABSTRACT FROM AUTHOR]

Background: Ascorbic acid (AA), uric acid (UA), and dopamine (DA) play crucial roles in human metabolism. These substances coexist in biological fluids, and their levels are directly associated with various pathologies. A significant problem encountered in the direct and simultaneous electrochemical detection of AA, UA, and DA is that these species present very close oxidation potentials on most electrode materials, leading to an overlap in the voltammetric response. Aim: The main goal of this work was to determine the concentration of AA, UA, and DA in a natural water sample on a carbon nanotube paste electrode (CNTPE). Methods: All voltammetric measurements were performed on a µAutolab potentiostat/galvanostat (Metrohm) connected to an electrochemical cell of three electrodes: working, reference (Ag/AgCl, KCl3.0M), and auxiliary (platinum). The working electrode was handmade in our laboratory. The following proportions were used to prepare the paste: 50% CNT + 50% mineral oil and 65% CNT + 35% mineral oil. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were used for the electroanalytical study. Results: The linear ranges for the simultaneous determination of AA, DA, and UA by DPV were: 0.45 - 1.0 mM, 50 - 200 μM, and 10 - 90 μM, respectively. The LODs of the proposed method for AA, DA, and UA were: 7.97 mM; 8.57 μM, and 5.96 μM, respectively. The relative standard deviations (RSD) were 4.6, 2.8, and 1.6% for 0.45 mM of AA, 50 μM of DA, and 50 μM of UA. Discussion: The oxidation mechanism of: AA, UA, and DA is a process that involves two electrons and 2 protons. Electrochemical detection of DA in the presence of high levels of AA on carbon-based electrodes becomes difficult due to the catalytic oxidation of AA by DA. For the three molecules, AA, UA, and DA, it is observed that the oxidation peak currents increased with increasing concentration. Conclusions: CNTPE allowed the separation of the oxidation peaks of the ternary mixture of AA, UA, and DA by cyclic voltammetry and, when associated with DPV allowed the simultaneous quantitative determination of AA, UA, and DA. [ABSTRACT FROM AUTHOR]