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We present a method to modify carbon fiber microelectrodes (CFME) with porous carbon nanofibers (PCFs) to improve detection and to investigate the impact of porous geometry for dopamine detection with fast-scan cyclic voltammetry (FSCV). PCFs were fabricated by electrospinning, carbonizing, and pyrolyzing poly-(acrylonitrile)-b-poly-(methyl methacrylate) (PAN-b-PMMA) block copolymer nanofiber frameworks. Commonly, porous nanofibers are used for energy storage applications, but we present an application of these materials for biosensing, which has not been previously studied. This modification impacted the topology and enhanced redox cycling at the surface. PCF modifications increased the oxidative current for dopamine (2.0 ± 0.1)-fold (n = 33) with significant increases in detection sensitivity. PCFs are known to have more edge plane sites which we speculate lead to the 2-fold increase in electroactive surface area. Capacitive current changes were negligible, providing evidence that improvements in detection are due to faradaic processes at the electrode. The ΔEp for dopamine decreased significantly at modified CFMEs. Only a 2.2 ± 2.2% change in dopamine current was observed after repeated measurements and only 10.5 ± 2.8% after 4 h, demonstrating the stability of the modification over time. We show significant improvements in norepinephrine, ascorbic acid, adenosine, serotonin, and hydrogen peroxide detection. Lastly, we demonstrate that the modified electrodes can detect endogenous, unstimulated release of dopamine in living slices of rat striatum. Overall, we provide evidence that porous nanostructures significantly improve neurochemical detection with FSCV and echo the necessity for investigating the extent to which geometry impacts electrochemical detection. [ABSTRACT FROM AUTHOR]

The second-generation antipsychotic drugs are widely used in the field of psychiatry, for an expanding number of different conditions. While their clinical efficacy remains indispensable, many of the drugs can cause severe metabolic side-effects, resulting in an increased risk of developing cardiometabolic disorders. The physiological basis of these side-effects remains an ongoing area of investigation. In the present study, we examined the potential role of peripheral catecholamines in antipsychotic-induced glucose intolerance. Adult female rats were acutely treated with either the first-generation antipsychotic drug haloperidol (0.1, 0.5 or 1 mg/kg) or the second-generation drugs risperidone (0.25, 1.0 or 2.5 mg/kg), olanzapine (1.5, 7.5 or 15 mg/kg) or clozapine (2, 10 or 20 mg/kg) or vehicle. Fasting glucose levels were measured and then animals were subjected to the intraperitoneal glucose tolerance test. Levels of peripheral norepinephrine, epinephrine and dopamine were concurrently measured in the same animals 75, 105 and 135 min after drug treatment. All antipsychotics caused glucose intolerance, with strongest effects by clozapine > olanzapine > risperidone > haloperidol. Plasma catecholamines were also increased by drug treatment, with greatest effects for norepinephrine and epinephrine caused by clozapine > risperidone > olanzapine > haloperidol. Importantly, there were strong and statistically significant associations between norepinephrine/epinephrine levels and glucose intolerance for all drugs. These findings confirm that increases in peripheral catecholamines co-occur in animals that exhibit antipsychotic-induced glucose intolerance, and these effects are strongly associated with each other, providing further evidence for elevated catecholamines as a substrate for antipsychotic metabolic side-effects. [ABSTRACT FROM AUTHOR]

This is the first part of a scientific statement from the Heart Failure Association (HFA) of the European Society of Cardiology focused upon the pathophysiology of Takotsubo syndrome and is complimentary to the previous HFA position statement on Takotsubo syndrome which focused upon clinical management. In part 1 we provide an overview of the pathophysiology of Takotsubo syndrome and fundamental questions to consider. We then review and discuss the central role of catecholamines and the sympathetic nervous system in the pathophysiology, and the direct effects of high surges in catecholamines upon myocardial biology including β‐adrenergic receptor signalling, G‐protein coupled receptor kinases, cardiomyocyte calcium physiology, myofilament physiology, cardiomyocyte gene expression, myocardial electrophysiology and arrhythmogenicity, myocardial inflammation, metabolism and energetics. The integrated effects upon ventricular haemodynamics are discussed and integrated into the pathophysiological model. [ABSTRACT FROM AUTHOR]

Renal α2-adrenoceptors have been reported to play a role in the regulation of urinary output, renin secretion, and water and sodium excretion in the kidneys. However, the distribution of α2-adrenoceptor subtypes in the kidneys remains unclear. In this study, we aimed to investigate the localization of α2-adrenoceptor subtypes in rat kidneys using 8-week-old Sprague–Dawley rats. Immunofluorescence imaging revealed that both α2A- and α2B-adrenoceptors were expressed in the basolateral, but not apical, membrane of the epithelial cells of the proximal tubules. We also found that α2A- and α2B-adrenoceptors were not expressed in the glomeruli, collecting ducts, or the descending limb of the loop of Henle and vasa recta. In contrast, α2C-adrenoceptors were found to be localized in the glomeruli and lumen of the cortical and medullary collecting ducts. These results suggest that noradrenaline may act on the basement membrane of the proximal tubules through α2A- and α2B-adrenoceptors. Moreover, noradrenaline may be involved in the regulation of glomerular filtration and proteinuria through the induction of morphological changes in mesangial cells and podocytes via α2C-adrenoceptors. In the collecting ducts, urinary noradrenaline may regulate morphological changes of the microvilli through α2C-adrenoceptors. Our findings provide an immunohistochemical basis for understanding the cellular targets of α2-adrenergic regulation in the kidneys. This may be used to devise therapeutic strategies targeting α2-adrenoceptors. [ABSTRACT FROM AUTHOR]

Phaeochromocytomas/paragangliomas (PPGL) are rare tumours that can cause cardiovascular complications following the secretion of catecholamines. We present a young female presented with heart failure with reduced ejection fraction as a result of norepinephrine secreting para‐aortic paraganglioma and improvement of heart failure sign and symptoms and left ventricular ejection fraction following tumour resection. [ABSTRACT FROM AUTHOR]

The aim of this study was to observe the effects of remifentanil on organ damage and energy metabolism in lipopolysaccharide (LPS)-induced septic rats. A total of 45 clean-grade male Wistar rats (weight 270-320 g) were randomly divided into three groups: a control group, an LPS group, and an LPS with remifentanil treatment (LPS+REM) group. After 6 hours of modeling, the levels of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in lung and kidney tissues of rats in each group were detected by ELISA. The activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in lung and kidney tissues were determined, and the content of lactic acid, pyruvate and epinephrine in heart and kidney tissues were detected. Reverse transcription polymerase chain reaction and the Western blot test were used to detect the expression of pyruvate dehydrogenase kinase 4 (PDK4) in the myocardial tissue. We found that remifentanil treatment inhibited the levels of IL-6, TNF-α, and MDA in the lung and kidneys 6 h after the administration of LPS and increased the level of SOD activity. Treatment with remifentanil reduced the expression of lactic acid, pyruvate, and epinephrine in the heart and kidney tissues and attenuated the expression of PDK4 messenger RNA and PDK4 protein in the myocardial tissue. We concluded that remifentanil mignt inhibit the release of tissue inflammatory factors, regulate the body's energy metabolism, and ultimately protect the sepsis tissue damage caused by LPS. [ABSTRACT FROM AUTHOR]

Abstract Increased sympathetic nervous system (SNS) activity leads to increased risk of cardiovascular morbidity and mortality. This study investigated whether there were sex differences in SNS activity among Chinese patients with hypertension. Ethnic Chinese non‐diabetic hypertensive patients aged 20–50 years were enrolled in Taiwan. A total of 970 hypertensive patients (41.0 ± 7.2 years) completed the study, 664 men and 306 women. They received comprehensive evaluations including office blood pressure (BP) measurement, 24‐h ambulatory BP monitoring, and 24‐h urine sampling assayed for catecholamine excretion. Compared to women, men were younger, had higher body mass index (BMI), office systolic BP (SBP), office diastolic BP (DBP), 24‐h ambulatory BP, and 24‐h urine catecholamine excretion. In men, 24‐h urine total catecholamine levels were correlated with 24‐h SBP (r = 0.103, p = .008) and 24‐h DBP (r = 0.083, p = .033). In women, however, there was no correlation between 24‐h urine total catecholamine levels and 24‐h ambulatory BP. Multivariate linear regression indicated that being male (β = 1.65, 95% confidence interval [CI] 0.01–3.29, p = .048) and 24‐h urine total catecholamine (β = 5.03, 95% CI 0.62–9.44, p = .025) were both independently associated with 24‐h SBP; being male was independently associated with 24‐h DBP (β = 3.55, 95% CI 2.26–4.85, p

Thanks to its simplicity, versatility, and secondary reactivity, dopamine self-polymerized coatings (pDA) have been widely used in surface modification of biomaterials, but the limitation in secondary molecular grafting and the high roughness restrain their application in some special scenarios. Therefore, some other catecholamine coatings analog to pDA have attracted more and more attention, including the smoother poly-norepinephrine coating (pNE), and the poly-levodopa coating (pLD) containing additional carboxyl groups. However, the lack of a systematic comparison of the properties, especially the biological properties of the above three catecholamine coatings, makes it difficult to give a guiding opinion on the application scenarios of different coatings. Herein, we systematically studied the physical, chemical, and biological properties of the three catecholamine coatings, and explored the feasibility of their application for the modification of biomaterials, especially cardiovascular materials. Among them, the pDA coating was the roughest, with the largest amount of amino and phenolic hydroxyl groups for molecule grafting, and induced the strongest platelet adhesion and activation. The pLD coating was the thinnest and most hydrophilic but triggered the strongest inflammatory response. The pNE coating was the smoothest, with the best hemocompatibility and histocompatibility, and with the strongest cell selectivity of promoting the proliferation of endothelial cells while inhibiting the proliferation of smooth muscle cells. To sum up, the pNE coating may be a better choice for the surface modification of cardiovascular materials, especially those for vascular stents and grafts, but it is still not widely recognized.

Abstract Post cardiac arrest syndrome is associated with high morbidity and mortality, which is related not only to a poor neurological outcome but also to respiratory and cardiovascular dysfunctions. The control of gas exchange, and in particular oxygenation and carbon dioxide levels, is fundamental in mechanically ventilated patients after resuscitation, as arterial blood gases derangement might have important effects on the cerebral blood flow and systemic physiology. In particular, the pathophysiological role of carbon dioxide (CO2) levels is strongly underestimated, as its alterations quickly affect also the changes of intracellular pH, and consequently influence metabolic energy and oxygen demand. Hypo/hypercapnia, as well as mechanical ventilation during and after resuscitation, can affect CO2 levels and trigger a dangerous pathophysiological vicious circle related to the relationship between pH, cellular demand, and catecholamine levels. The developing hypocapnia can nullify the beneficial effects of the hypothermia. The aim of this review was to describe the pathophysiology and clinical consequences of arterial blood gases and pH after cardiac arrest. According to our findings, the optimal ventilator strategies in post cardiac arrest patients are not fully understood, and oxygen and carbon dioxide targets should take in consideration a complex pattern of pathophysiological factors. Further studies are warranted to define the optimal settings of mechanical ventilation in patients after cardiac arrest.

Cardiotoxicity remains the most common reason for failure during drug development. Recently, the zebrafish (Danio rerio) model has emerged for the evaluation of drug-dependent cardiotoxicity and for the identification of cardioprotective molecules. However, it remains unknown how closely the zebrafish-based results may be translated to humans. To tackle this issue, we established embryonic zebrafish models of doxorubicin-, adrenaline- and terfenadine-induced cardiotoxicity with unified dosing regimen which eventually enabled head-to-head comparison of the drugs. Subsequently, we determined whether human cardioprotective medications – dexrazoxane, metoprolol, carvedilol and valsartan – are able to manage heart dysfunction in zebrafish. Our results indicated that doxorubicin, adrenaline and terfenadine elicited overt signs of cardiotoxicity in fish, and we further showed that the blockade of the renin-angiotensin system and, to a lesser extent, β-adrenergic system, ameliorated the heart disease in zebrafish. From the drug development standpoint, our work opens the possibility to determine the cardiovascular properties of tested compounds using the rapid and affordable zebrafish model.

Pheochromocytoma is a rare catecholamine-secreting tumor with highly variable clinical presentations. We herein report a patient who presented to the emergency department with precordia pain, elevated myocardial enzymes, T-wave inversions on electrocardiogram and segmental ventricular wall motion abnormalities on echocardiography, which is normally managed as suspected acute coronary syndrome (ACS). However, the urgent coronary angiography showed normal coronary arteries. During his hospital stay, a sudden increase in blood pressure allowed us to suspect a pheochromocytoma, which was confirmed by elevated levels of catecholamines and by the finding of a right adrenal mass on magnetic resonance imaging. The tumor was successfully excised and the patient is now asymptomatic. This case illustrates that pheochromocytoma can present as a mimic of ACS but this is often difficult to diagnose at first glance and often misleads clinicians into making an incorrect diagnosis. In addition, clinicians should be familiar with clinical manifestations of pheochromocytoma, which can help raise clinical suspicion and facilitate the early diagnosis and treatment of pheochromocytoma.

Head and neck paragangliomas (HNPGLs) are neuroendocrine tumors. They arise from the parasympathetic ganglia and can be either sporadic or due to hereditary syndromes (up to 40%). Most HNPGLs do not produce significant amounts of catecholamines. We report a case of a giant paraganglioma of the skull base with an unusually severe presentation secondary to excessive release of norepinephrine, with a good outcome considering the severity of disease. A 39-year-old Caucasian woman with no prior medical history was found unconscious and emaciated in her home. In the intensive care unit (ICU) the patient was treated for multi-organ failure with multiple complications and difficulties in stabilizing her blood pressure with values up to 246/146 mmHg. She was hospitalized in the ICU for 72 days and on the 31st day clinical assessment revealed jugular foramen syndrome and paralysis of the right n. facialis. A brain MRI confirmed a right-sided tumor of the skull base of 93.553 cm3. Blood tests showed high amounts of normetanephrine (35.1-45.4 nmol/L, ref G, p.C189G) and PTEN (c.834C>G, p.F278L) missense mutation in tumor DNA. The patient made a remarkable recovery except for neurological deficits after intensive multidisciplinary treatment and rehabilitation. This case demonstrates the necessity for an early tertiary center approach with a multidisciplinary expert team and highlights the efficacy of the correct treatment with alpha-blockade.

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

Severe traumatic injury results in a cascade of systemic changes which negatively affect normal erythropoiesis. Immediately after injury, acute blood loss leads to anemia, however, patients can remain anemic for as long as 6 months after injury. Research on the underlying mechanisms of such alterations of erythropoiesis after trauma has focused on the prolonged hypercatecholaminemia seen after trauma. Supraphysiologic elevation of catecholamines leads to an inhibitive effect on erythropoiesis. There is evidence to show that alleviation of the neuroendocrine stress response following trauma reduces these inhibitory effects. Both beta blockade and alpha-2 adrenergic receptor stimulation have demonstrated increased growth of hematopoietic progenitor cells as well as increased pro-erythropoietic cytokines after trauma. This review will describe prior research on the neuroendocrine stress response after trauma and its consequences on erythropoiesis, which offer insight into underlying mechanisms of prolonged anemia postinjury. We will then discuss the beneficial effects of adrenergic modulation to improve erythropoiesis following injury and propose future directions for the field.

Ganglioneuromas (GNs) are benign tumors that originate from neural crest cells, composed mainly of mature ganglion cells. These tumors, which are usually hormonally silent, tend to be discovered incidentally on imaging tests and occur along the paravertebral sympathetic chain, from the neck to the pelvis and occasionally in the adrenal medulla. Rarely, GNs secrete catecholamines.1 Adrenal GNs occur most frequently in the fourth and fifth decades of life, whereas GNs of the retroperitoneum and posterior mediastinum are usually encountered in younger adults.2 Adrenal GNs are commonly hormonally silent and asymptomatic; even when the lesion is of substantial size.3 We report an incidentally detected asymptomatic case of an adrenal ganglioneuroma with mildly elevated urinary catecholamine levels in an elderly male. After preoperative alpha blockade, the patient underwent open right adrenalectomy. Upon microscopic examination, the right adrenal mass proved to be a ganglioneuroma, maturing type and the immunohistochemistry examination showed immunoreactivity to synaptophysin, chromogranin, and CD 56, while S100 was strongly positive at the Schwannian stroma. Following resection, catecholamine levels normalized, confirming the resected right adrenal ganglioneuroma as the source of the catecholamine excess. This case represents a rare presentation of catecholamine-secreting adrenal ganglioneuroma in the elderly.

Background Obesity is an established risk factor for hypertension. Although obesity‐induced gut barrier breach leads to the leakage of various microbiota‐derived products into host circulation and distal organs, the roles of microbiota in mediating the development of obesity‐associated adrenomedullary disorders and hypertension have not been elucidated. We seek to explore the impacts of microbial DNA enrichment on inducing obesity‐related adrenomedullary abnormalities and hypertension. Methods and Results Obesity was accompanied by remarkable bacterial DNA accumulation and elevated inflammation in the adrenal glands. Gut microbial DNA containing extracellular vesicles (mEVs) were readily leaked into the bloodstream and infiltrated into the adrenal glands in obese mice, causing microbial DNA enrichment. In lean wild‐type mice, adrenal macrophages expressed CRIg (complement receptor of the immunoglobulin superfamily) that efficiently blocks the infiltration of gut mEVs. In contrast, the adrenal CRIg+ cell population was greatly decreased in obese mice. In lean CRIg−/− or C3−/− (complement component 3) mice intravenously injected with gut mEVs, adrenal microbial DNA accumulation elevated adrenal inflammation and norepinephrine secretion, concomitant with hypertension. In addition, microbial DNA promoted inflammatory responses and norepinephrine production in rat pheochromocytoma PC12 cells treated with gut mEVs. Depletion of microbial DNA cargo markedly blunted the effects of gut mEVs. We also validated that activation of cGAS (cyclic GMP‐AMP synthase)/STING (cyclic GMP–AMP receptor stimulator of interferon genes) signaling is required for the ability of microbial DNA to trigger adrenomedullary dysfunctions in both in vivo and in vitro experiments. Restoring CRIg+ cells in obese mice decreased microbial DNA abundance, inflammation, and hypertension. Conclusions The leakage of gut mEVs leads to adrenal enrichment of microbial DNA that are pathogenic to induce obesity‐associated adrenomedullary abnormalities and hypertension. Recovering the CRIg+ macrophage population attenuates obesity‐induced adrenomedullary disorders.

The second-generation antipsychotic drugs are widely used in the field of psychiatry, for an expanding number of different conditions. While their clinical efficacy remains indispensable, many of the drugs can cause severe metabolic side-effects, resulting in an increased risk of developing cardiometabolic disorders. The physiological basis of these side-effects remains an ongoing area of investigation. In the present study, we examined the potential role of peripheral catecholamines in antipsychotic-induced glucose intolerance. Adult female rats were acutely treated with either the first-generation antipsychotic drug haloperidol (0.1, 0.5 or 1 mg/kg) or the second-generation drugs risperidone (0.25, 1.0 or 2.5 mg/kg), olanzapine (1.5, 7.5 or 15 mg/kg) or clozapine (2, 10 or 20 mg/kg) or vehicle. Fasting glucose levels were measured and then animals were subjected to the intraperitoneal glucose tolerance test. Levels of peripheral norepinephrine, epinephrine and dopamine were concurrently measured in the same animals 75, 105 and 135 min after drug treatment. All antipsychotics caused glucose intolerance, with strongest effects by clozapine > olanzapine > risperidone > haloperidol. Plasma catecholamines were also increased by drug treatment, with greatest effects for norepinephrine and epinephrine caused by clozapine > risperidone > olanzapine > haloperidol. Importantly, there were strong and statistically significant associations between norepinephrine/epinephrine levels and glucose intolerance for all drugs. These findings confirm that increases in peripheral catecholamines co-occur in animals that exhibit antipsychotic-induced glucose intolerance, and these effects are strongly associated with each other, providing further evidence for elevated catecholamines as a substrate for antipsychotic metabolic side-effects.

Catecholamine release increases in dogs with pheochromocytomas and in situations of stress. Although plasma catecholamines degrade rapidly, their metabolites, normetanephrine (NME) and metanephrine (ME), are stable in acidified urine. Our aim was to verify a human urine ELISA kit for the quantification of NME and ME in canine urine and to determine the effects on metabolite stability of sampling time (morning or midday) and day (ordinary or day spent in a clinic). We analyzed 179 urine samples from 17 healthy dogs. For NME, the mean intra-assay CV was 6.0% for all samples and 4.3% for the canine control; inter-assay CVs were 3.3, 3.8, and 12% for high and low concentration human urine positive controls supplied in the ELISA kit and a positive canine control, respectively; spike-recovery was 90–101%. For ME, mean intra-assay CV was 6.5% for samples and 9.0% for the canine control; inter-assay CVs were 12.7, 7.2, and 22.5% for high and low concentration human urine positive controls supplied in the ELISA kit and a positive canine control, respectively; spike-recovery was 85–89%. Dilution recovery was unsatisfactory for both metabolites. Based on our verification results, NME was selected for remaining analyses. We found no effect on NME concentrations of acidification or room temperature storage for up to 24 h. The NME:creatinine ratio was higher after the first of 3 clinic days compared to the same morning (111.2 ± 5.5 vs. 82.9 ± 5.3; p < 0.0001), but not on the other days. NME verification results were generally superior to ME. Dilution studies were unsatisfactory for both metabolites. Given that NME was stable without acidification at room temperature, urine samples can be collected at home. The clinic environment can cause higher NME:creatinine ratios, especially in unaccustomed dogs. [ABSTRACT FROM AUTHOR]

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Aim: Pheochromocytomas are neuroendocrine tumors originating from chromaffin cells. The aim of the current study is to review the clinical, laboratory, and imaging findings of pheochromocytoma. Material and Method: Clinical, laboratory, and radiological data of a total of 19 patients diagnosed with pheochromocytoma between 2009-2019 were evaluated retrospectively. Results: Of the 19 patients diagnosed with pheochromocytoma, 13 were female, and 6 were male, and the mean age of 44.1±11.3 years. Hypertension was present in 18 patients, of which 8 were newly diagnosed. It was found that thyroid pathologies were most common after hypertension in patients with pheochromocytoma. The most common symptom after high blood pressure was sweating and headache. All patients had vitamin D deficiency or insufficiency. In 94.1% of patients, the level of normetanephrine observed was found to be elevated. 11 were right-sided, 5 were left-sided, and the remaining 3 were bilateral. The lesion size was less than 4 cm in 36.8%, between 4-6 cm in 42.1%, and greater than 6 cm in 21.1%. Conclusion: In the current study showed that pheochromocytoma has a nonspecific and variable clinic feature. In patients with suspected pheochromocytoma, 24-hour urine normetanephrine and metanephrine levels should be requested as a screening test, especially during attacks, and surgical treatment should be performed after the mass is localized with imaging methods. [ABSTRACT FROM AUTHOR]

Summary: Our human observational study showed that elevated arginine vasopressin levels by heavy exercise, not catecholamines, were associated with elevated serum tartrate-resistant acid phosphatase 5b (TRACP-5b). The increase in serum calcium was positively associated with percent changes of TRACP-5b, implying the involvement of bone resorption in the pathogenesis of exercise-induced hypercalcemia. Introduction: It remains unclear whether enhanced bone resorption explains exercise-induced hypercalcemia. An experimental study demonstrated that arginine vasopressin (AVP) stimulated osteoclast activity. Methods: We conducted a prospective observational study, enrolling 65 trained healthy male officers of the Japan Self-Defense Forces (34 and 31 in waves 1 and 2, respectively). Before and after a 5-h heavy exercise, we collected laboratory data including bone markers, symptoms, and ionized calcium (iCa; wave 2 only). As blood calcium levels change after exercise, we estimated calcium (corrected calcium) levels immediately after the exercise using the correlation between blood calcium and time from the end of exercise in another cohort. Results: Body weight decreased by 6.9% after the exercise. Corrected post-exercise serum total calcium (tCa) and iCa levels were significantly higher than pre-exercise levels, and 18% of participants showed hypercalcemia defined as corrected tCa >10.4 mg/dL or iCa >1.30 mmol/L. Serum tartrate-resistant acid phosphatase 5b (TRACP-5b), plasma three fractions of catecholamines, and AVP elevated significantly (median 14.3 pg/mL), while procollagen type 1 N-terminal propeptide and whole parathyroid hormone showed significant decreases. Corrected tCa increase showed a non-linear positive association with percent changes of TRACP-5b (%ΔTRACP-5b) even after adjustment for confounders. In addition, %ΔTRACP-5b was not associated with catecholamines, but with post-exercise AVP levels after adjustment for pre-exercise TRACP-5b. Symptoms of nausea or vomiting (observed in 20%) were positively associated with corrected post-exercise iCa after adjustment for post-exercise blood pH. Conclusion: AVP elevation may explain bone resorption and the following hypercalcemia in the setting of heavy exercise. [ABSTRACT FROM AUTHOR]

We examined potential changes in catecholamine plasma levels and cortisol serum levels in 29 patients with treatment-resistant Major Depressive Disorder (MDD) during a course of electroconvulsive therapy (ECT). Blood samples were taken at three different time points: directly before (T1) and 15 min after (T2) the first ECT, and directly before the last one (T3). Patients responding to ECT had a significant decrease of the intraindividual epinephrine plasma level when both first time points (Δ T1-T2) were compared (χ2 (1) = 10.05, p = 0.002). This finding encourages further investigation in the understanding of the catecholamine-metabolism including its release and uptake in patients with treatment-resistant MDD receiving ECT. [ABSTRACT FROM AUTHOR]

Objective: Several guidelines recommend oral administration of nimodipine as vasospasm prophylaxis after aneurysmal subarachnoid hemorrhage (SAH). However, in clinical practice, the drug is administered orally and intravenously (i.v.), depending on clinical conditions and local treatment regimens. We have therefore investigated the safety and clinical effects of switching from i.v. to oral nimodipine therapy. Methods: Patients with aneurysmal SAH between January 2014 and April 2018 and initial i.v. nimodipine therapy, which was subsequently switched to oral administration, were included in this retrospective study. Transcranial Doppler sonography (TCD) of the vessels of the anterior circulation was performed daily. The occurrence of vasospasm and infarction during the overall course of the treatment was recorded. Statistical level of significance was set to p < 0.05. Results: A total of 133 patients (mean age 55.8 years, 65% female) initially received nimodipine i.v. after aneurysmal SAH, which was subsequently switched to oral administration after a mean of 12 days. There were no significant increases in mean flow velocities on TCD after the switch from i.v. to oral nimodipine administration regarding the anterior cerebral artery. For the middle cerebral artery, an increase from 62.36 to 71.78 cm/sec could only be detected in the subgroup of patients with infarction. There was no clustering of complicating events such as new-onset vasospasm or infarction during or after the switch. Conclusions: Our results do not point to any safety concerns when switching nimodipine from initial i.v. to oral administration. Switching was neither associated with clinically relevant increases in TCD velocities nor other relevant adverse events. [ABSTRACT FROM AUTHOR]

The brain influences liver metabolism through many neuroendocrine and autonomic mechanisms that have evolved to protect the organism against starvation and hypoglycemia. Unfortunately, this effective way of preventing death has become dysregulated in modern obesogenic environments, although the pathophysiological mechanisms behind metabolic dyshomeostasis are still unclear. In this Mini-Review, we provide our thoughts regarding obesity and type 2 diabetes as diseases of the autonomic nervous system. We discuss the pathophysiological mechanisms that alter the autonomic brain-liver communication in these diseases, and how they could represent important targets to prevent or treat metabolic dysfunctions. We discuss how sympathetic hyperactivity to the liver may represent an early event in the progression of metabolic diseases and could progressively lead to hepatic neuropathy. We hope that this discussion will inspire and help to frame a model based on better understanding of the chronology of autonomic dysfunctions in the liver, enabling the application of the right strategy at the right time. [ABSTRACT FROM AUTHOR]

Ganglioneuroma, which arise from neural crest cells, typically occurs in adolescents and young adults. Most ganglioneuromas are clinically asymptomatic and hormonally silent, therefore may be diagnosed incidentally during imaging studies. Ganglioneuroma containing fat (lipomatous ganglioneuroma) is a rare variant of ganglioneuroma that is histologically characterized by a mature adipocytic component admixed with a conventional ganglioneuroma. Herein, we report the case of adrenal lipomatous ganglioneuroma with elevated urinary catecholamine level.

Objective To investigate the effect of stress hormones on cell cycle re-entry of G0 phase in mouse H22 hepatocarcinoma cells. Methods Flow cytometry antibody staining with CD44 and CD133 was used to determine the presence of cancer stem cells in H22 cells. In vitro, after treatment of H22 cells with stress hormone corticosterone (CORT), epinephrine (EPI) and norepinephrine (NE) for 48 h, the proportion changes of cells in G0 phase and cell cycle distribution were detected by Ki-67 and PI flow cytometry staining. The hormone receptor antagonists were used to verify the receptor subtypes that mediated the cell cycle re-entry of G0 phase cells. Results The proportion of cancer stem cells (CD44+CD133+) in H22 cells was 0.80%±0.15%. Compared with control group, the portion of G0 phase cells was unchanged after corticosterone treatment, but was decreased by 62.50% and 53.00% respectively after EPI and NE treatment. Meanwhile, the total cells, proportion of G2/M and S phase cells were increased compared to control group. The protein expression of Skp2 was increased and p27kip1 decreased significantly after EPI and NE treatment(P＜0.05). In addition, α1-adrenergic receptor antagonists terazosin and prazosin blocked the G0 phase cells cycle re-entry effect of EPI and NE. The protein expression of Skp2 was decreased and p27kip1 was increased significantly after prazosin treatment compared to EPI or NE group(P＜0.05). Conclusions Catecholamine stress hormones mediate the cell cycle re-entry of G0 phase cells in mouse H22 hepatocarcinoma cells by activating α1-adrenergic receptor,the mechanism of which may be associated with the Skp2 over-expression and the degradation of p27kip1 protein.

Dyana Sarvasti,1 Isabella Lalenoh,2 Emanoel Oepangat,2 Budhi Setianto Purwowiyoto,3 Anwar Santoso,3 Rochmad Romdoni4 1Department of Internal Medicine, Faculty of Medicine Widya Mandala Catholic University, Surabaya, Indonesia; 2Department of Cardiology, Siloam Hospital TB Simatupang, Jakarta, Indonesia; 3Department of Cardiology and Vascular Medicine, Faculty of Medicine University of Indonesia National Cardiovascular Center Harapan Kita, Jakarta, Indonesia; 4Department of Cardiology and Vascular Medicine, Faculty of Medicine Airlangga University - Dr. Soetomo District General Hospital, Surabaya, IndonesiaCorrespondence: Dyana SarvastiDepartment of Internal Medicine, Faculty of Medicine Widya Mandala Catholic University Jl, Raya Kalisari Selatan No. 1 Tower A, Lt. 6, Pakuwon City, Surabaya 60112, IndonesiaTel +628563000696Email dyana_sarvasti@yahoo.comPurpose: Our study aimed at determining and comparing the mechanism of cardiovascular protection variables in moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) in patients with stable coronary heart disease (CHD) after coronary stenting.Participants and Methods: This experimental study used the same subject and cross-over design, involving eleven stable CHD patients after coronary stenting. These were randomly divided into two groups; MICT for 29 minutes at 50– 60% heart rate reserve and HIIT with 4x4 minute intervals at 60– 80% heart rate reserve, each followed by three minutes of active recovery at 40– 50% heart rate reserve. These were conducted three times a week for two weeks. The participants’ levels of adrenaline, noradrenaline, endothelial nitric oxide synthase (eNOS), extracellular superoxide dismutase (EC-SOD) activity assayed, and flow-mediated dilatation (FMD) were examined before and after treatments were completed.Results: The HIIT significantly increased the levels of noradrenaline and eNOS compared with MICT (p< 0.05). Also, HIIT was better in maintaining EC-SOD activity and FMD compared with MICT (p< 0.05). Through the noradrenalin pathway, HIIT had a direct and significant effect on eNOS and FMD (p< 0.05) but MICT, through the noradrenaline pathways, had a direct and significant effect on eNOS (p< 0.05), and through the EC-SOD activity pathways had a direct and significant effect on FMD (p< 0.05). MICT reduced EC-SOD activity and also decreased the FMD value.Conclusion: HIIT is superior to MICT in increasing cardiovascular protection by increasing the concentrations of noradrenalin and eNOS, maintaining EC-SOD activity, and FMD in stable CHD patients after coronary stenting.Keywords: coronary heart disease, high-intensity interval training, catecholamine, eNOS, SOD, FMD

Renalase is predominantly expressed in the kidney, where it plays a role in catecholamine metabolism and blood pressure regulation. Moderate‐intensity exercise (MEX) has been shown to increase the concentration of renalase in the blood and to reduce renal function in humans. Moreover, such exercise was also reported to increase catecholamine levels. Here, we examined renalase concentration in the blood and renalase expression levels in different organs after MEX in rats. Twelve male Wistar rats were made to run on a treadmill (MEX group) for 60 min at 20 m·min−1, after resting for 15 min. The control group rats were euthanized after resting on the treadmill. Tissue and blood samples were analyzed using western blotting, real‐time RT‐PCR and ELISA. Overall, the concentrations of renalase in the blood were significantly higher in the MEX group than that in the control group. Renalase expression was decreased in the kidney after 60 min of exercise, whereas the expression of renalase mRNA and protein in the extensor digitorum longus and plantaris muscles, respectively, increased after exercise. However, the expression of renalase in the other tissues examined did not change after acute exercise. In conclusion, we report that MEX for 60 min increases both renalase concentration in the blood and its expression in skeletal muscle.

We investigated changes in the basic parameter of physiological stress such as catecholamine and heart rate, blood pressure during the ascent of one-day Mt. Fuji hiking via the Fujinomiya Trail. Six Japanese healthy young adult males (age: 21 ± 1 years) volunteered to hike Mt. Fuji (altitude: 3,776 m) located in Shizuoka Prefecture in August 2014. The weather was fine. Heart rate (HR), arterial oxygen saturation (SpO2), blood pressure (SBP/DBP), double product (DP), urinary adrenaline (AD) · urinary noradrenaline (NA) and creatinine (Cr) were measured at a point near sea level (Pre: altitude 9 m) and during the ascent. HR, AD/Cr, NA/Cr and DP at the summit were significantly higher and SpO2 was significantly lower than those of Pre and 5th Station (altitude: 2,400 m). AD/Cr and NA/Cr at the 5th Station were significantly higher than those of Pre (values at starting point near sea level). There was no significant change in SBP and DBP. As a significant positive correlation between changes in the indices of catecholamine (AD/Cr, NA/Cr) and HR, DP was observed during the ascent of one-day Mt. Fuji hiking (p

Abstract Background Catecholamines are the first-line vasopressors used in patients with septic shock. However, the search for novel drug candidates is still of great importance due to the development of adrenergic hyposensitivity accompanied by a decrease in catecholamine activity. Terlipressin (TP) is a synthetic vasopressin analogue used in the management of patients with septic shock. In the current study, we aimed to compare the effects of TP and catecholamine infusion in treating septic shock patients. Methods A systematic review and meta-analysis was conducted by searching articles published in PUBMED, EMBASE, and the Cochrane Central Register of Controlled Trials between inception and July 2018. We only selected randomized controlled trials evaluating the use of TP and catecholamine in adult patients with septic shock. The primary outcome was overall mortality. The secondary outcomes were the ICU length of stay, haemodynamic changes, tissue perfusion, renal function, and adverse events. Results A total of 9 studies with 850 participants were included in the analysis. Overall, no significant difference in mortality was observed between the TP and catecholamine groups (risk ratio(RR), 0.85 (0.70 to 1.03); P = 0.09). In patients

Gang Fang, Lizhi Niu, Jibing Chen Fuda Cancer Hospital of Jinan University, Guangzhou 510665, People’s Republic of ChinaCorrespondence: Jibing ChenFuda Cancer Hospital of Jinan University, No. 2 Of Tangdexi Road, Tianhe District, Guangzhou 510665, People’s Republic of ChinaEmail jibingchen398@163.comBackground and objective: When irreversible electroporation (IRE) ablation of abdominal tumors, procedural hypertension often occurs, which often affects the progress of the ablation. Until now, there is no reasonable explanation for this phenomenon. The objective of this research was to explore the cause and solution of procedural hypertension in percutaneous IRE.Methods: In this study, the treatment data of 4 consecutive groups of patients were used to confirm the cause of intraoperative hypertension and then verify the solution. A total of 155 patients with procedural hypertension were screened based on their medical records of pancreatic or hepatic IRE treatment. Procedural hypertension was monitored in 21 new patients, the correlation between serum catecholamines and hypertension was recorded and evaluated using regression analysis. Forty new patients were divided into two groups (distance from needle tip to adrenal gland, < 2 cm vs ≥ 2 cm), and the blood pressure was recorded and compared with two-way ANOVA. Eleven patients with ablative distance < 2 cm were treated in advance with phentolamine to observe for the occurrence of procedural hypertension.Results: Of the 21 re-enrolled patients with ablation of the pancreas and liver tumors, 9 developed intraoperative hypertension with significantly elevated serum catecholamines levels, epinephrine, norepinephrine and dopamine are all positively associated with hypertension, with P values were 0.0003, 0.0253, and 0.0015, respectively. For the two groups with different needle-insertion distances, hypertension in the < 2 cm group was more significant than that in the other group (for procedural hypertension, P< 0.01; for heart rate, P< 0.05), which was considered as a high-risk group. The occurrence of intraoperative hypertension could be completely prevented by using phentolamine prior to treatment.Conclusion: Hypertension occurs frequently during hepatic and pancreatic IRE because of the damage of adrenal gland. The safe distance of ablation probe for the adrenal gland was 2 cm. For high-risk patients, early drug prevention works well. Keywords: irreversible electroporation, abdominal tumor, procedural hypertension, adrenal gland, catecholamine, risky distance

Background and Aims: Surgery for pheochromocytoma (PCC) can cause excessive catecholamine release with severe hypertension. Alpha blockade is the mainstay of preoperative management. The aim of this study was to evaluate the efficacy and tolerance of intra-venous (IV) urapidil, a competitive short acting α1 receptor antagonist, in the prevention of peri-operative hemodynamic instability of patients with PCC. Material and Methods: This retrospective observational study included 75 patients (79 PCC) for PCC removal surgery from 2001 to 2017 at the Bordeaux University Hospital. They received, 3 days before surgery, continuous intravenous infusion of urapidil with stepwise increase to the maximum tolerated dose. Urapidil was maintained during the procedure and stopped after clamping the adrenal vein. Plasma catecholamine concentrations were measured during surgery. Hypertensive peaks (SAP >160 mmHg) and tachycardia >100 beats/min were treated with boluses of nicardipine 2 mg and esmolol 0.5 mg/kg. Results: We recorded 20/79 (25%) cases with systolic arterial pressure (SAP) >180 mmHg. Only 11/79 (14%) had hypotension with SAP

Recent reports indicate that Parkinson's disease (PD) involves specific functional abnormalities in residual neurons – decreased vesicular sequestration of cytoplasmic catecholamines via the vesicular monoamine transporter (VMAT) and decreased aldehyde dehydrogenase (ALDH) activity. This double hit builds up the autotoxic metabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL), the focus of the catecholaldehyde hypothesis for the pathogenesis of PD. An animal model is needed that reproduces this abnormal catecholamine neurochemical pattern. Adult rats received subcutaneous vehicle or the mitochondrial complex 1 inhibitor rotenone (2 mg/kg/day via a minipump) for 10 days. Locomotor activity was recorded, and striatal tissue sampled for catechol contents and catechol ratios that indicate the above abnormalities. Compared to vehicle, rotenone reduced locomotor activity (P=0.002), decreased tissue dopamine concentrations (P=0.00001), reduced indices of vesicular sequestration (3,4-dihydroxyphenylacetic acid (DOPAC)/dopamine) and ALDH activity (DOPAC/DOPAL) (P=0.0025, P=0.036), and increased DOPAL levels (P=0.04). The rat rotenone model involves functional abnormalities in catecholaminergic neurons that replicate the pattern found in PD putamen. These include a vesicular storage defect, decreased ALDH activity and DOPAL build-up. The rat rotenone model provides a suitable in vivo platform for studying the catecholaldehyde hypothesis.

Abstract Background Neurofibromatosis type 1 has a higher prevalence of pheochromocytoma and paraganglioma than the general population: 1.0–5.7% versus 0.2–0.6%. Currently, there are no generally accepted guidelines for screening for pheochromocytoma and paragangliomas in asymptomatic patients with neurofibromatosis type 1. Case presentation Severe hypertension developed during anesthesia induction in our patient, a 44-year-old Chinese man with neurofibromatosis type 1. We screened for catecholamine level after glioma resection, and the patient was diagnosed with combined pheochromocytoma and paraganglioma. Conclusions A delay in diagnosis or lack of a diagnosis in pheochromocytoma and paraganglioma may increase the perioperative morbidity and mortality risk due to excess catecholamine secretion. Therefore, routine pheochromocytoma and paraganglioma screening preoperatively in patients with neurofibromatosis type 1 is very important.

Abstract Despite interesting and unique pharmacological properties, levosimendan has not proven a clear superiority to placebo in the patient populations that have been enrolled in the various recent multicenter randomized controlled trials. However, the pharmacodynamic effects of levosimendan are still considered potentially very useful in a number of specific situations. Patients with decompensated heart failure requiring inotropic support and receiving beta-blockers represent the most widely accepted indication. Repeated infusions of levosimendan are increasingly used to facilitate weaning from dobutamine and avoid prolonged hospitalizations in patients with end-stage heart failure, awaiting heart transplantation or left ventricular assist device implantation. New trials are under way to confirm or refute the potential usefulness of levosimendan to facilitate weaning from veno-arterial ECMO, to treat cardiogenic shock due to left or right ventricular failure because the current evidence is mostly retrospective and requires confirmation with better-designed studies. Takotsubo syndrome may represent an ideal target for this non-adrenergic inotrope, but this statement also relies on expert opinion. There is no benefit from levosimendan in patients with septic shock. The two large trials evaluating the prophylactic administration of levosimendan (pharmacological preconditioning) in cardiac surgical patients with poor left ventricular ejection fraction could not show a significant reduction in their composite endpoints reflecting low cardiac output syndrome with respect to placebo. However, the subgroup of those who underwent isolated CABG appeared to have a reduction in mortality. A new study will be required to confirm this exploratory finding. Levosimendan remains a potentially useful inodilator agent in a number of specific situations due to its unique pharmacological properties. More studies are needed to provide a higher level of proof regarding these indications.

Pheochromocytoma multisystem crisis (PMC) is a potentially lethal emergency due to catecholamine secretion. The condition manifests as severe hypertension to intractable cardiogenic shock and has a high mortality rate. This study explored the efficacy and safety of applying chlorpromazine on PMC patients. The study included seven patients (median age, 42 years; range, 14–57 years) diagnosed with pheochromocytoma. Four consecutive PMC patients were admitted to our critical care unit between 2016 and 2020 due to abdominal or waist pain, nausea, and vomiting. Their blood pressure (BP) fluctuated between 200–330/120–200 and 40–70/30–50 mmHg. Chlorpromazine (25 or 50 mg) was injected intramuscularly, followed by continuous intravenous infusion (2–8 mg/h). The patients' BP decreased to 100–150/60–100 mmHg within 1–3 h and stabilized within 3–5 days. Two weeks later, surgical tumor resection was successfully performed in all four patients. Similar clinical outcomes were also obtained in three patients with sporadic PMC reported in the literature who received chlorpromazine treatment, which reduced their BP readings from >200/100 mmHg to 120/70 mmHg. Our observations, combined with sporadic reports, showed that chlorpromazine efficiently controlled PMC. Thus, future studies on the use of chlorpromazine are warranted.

Chronic stress is common among cancer patients due to the psychological, operative, or pharmaceutical stressors at the time of diagnosis or during the treatment of cancers. The continuous activations of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS), as results of chronic stress, have been demonstrated to take part in several cancer-promoting processes, such as tumorigenesis, progression, metastasis, and multi-drug resistance, by altering the tumor microenvironment (TME). Stressed TME is generally characterized by the increased proportion of cancer-promoting cells and cytokines, the reduction and malfunction of immune-supportive cells and cytokines, augmented angiogenesis, enhanced epithelial-mesenchymal transition, and damaged extracellular matrix. For the negative effects that these alterations can cause in terms of the efficacies of anti-cancer treatments and prognosis of patients, supplementary pharmacological or psychotherapeutic strategies targeting HPA, SNS, or psychological stress may be effective in improving the prognosis of cancer patients. Here, we review the characteristics and mechanisms of TME alterations under chronic stress, their influences on anti-cancer therapies, and accessory interventions and therapies for stressed cancer patients.

Tyramine (TRM) is a biogenic catecholamine neurotransmitter, which can trigger migraines and hypertension. TRM accumulated in foods is reduced and detected using additive cyclodextrins (CDs) while their association characteristics remain unclear. Here, single-crystal X-ray diffraction and density functional theory (DFT) calculation have been performed, demonstrating the elusive pseudopolymorphs in β-CD inclusion complexes with TRM base/HCl, β-CD·0.5TRM·7.6H 2 O ( 1 ) and β-CD·TRM HCl·4H 2 O ( 2 ) and the rare α-CD·0.5(TRM HCl)·10H 2 O ( 3 ) exclusion complex. Both 1 and 2 share the common inclusion mode with similar TRM structures in the round and elliptical β-CD cavities, belong to the monoclinic space group P 2 1 , and have similar herringbone packing structures. Furthermore, 3 differs from 2 , as the smaller twofold symmetry-related, round α-CD prefers an exclusion complex with the twofold disordered TRM-H + sites. In the orthorhombic P 2 1 2 1 2 lattice, α-CDs are packed in a channel-type structure, where the column-like cavity is occupied by disordered water sites. DFT results indicate that β-CD remains elliptical to suitably accommodate TRM, yielding an energetically favorable inclusion complex, which is significantly contributed by the β-CD deformation, and the inclusion complex of α-CD with the TRM aminoethyl side chain is also energetically favorable compared to the exclusion mode. This study suggests the CD implications for food safety and drug/bioactive formulation and delivery.

Background: It is extremely essential to accurately differentiate pheochromocytoma from Adrenal incidentalomas (AIs) before operation, especially biochemical tests were inconclusive. We aimed to evaluate the value of magnetic resonance imaging (MRI) features to differentiate pheochromocytomas among adrenal tumors, among which the consequences of biochemical screening tests of catecholamines and/or catecholamine metabolites are positive., Methods: With institutional review board approval, this study retrospectively compared 35 pheochromocytoma (PHEO) patients with 27 non-pheochromocytoma(non-PHEO) patients between January 2022 to September 2023, among which the consequences of biochemical screening tests of catecholamines and/or catecholamine metabolites are positive. T test was used for the independent continuous data and the chi-square test was used for categorical variables. Univariate and multivariate logistic regression were applied to find the independent variate of the features to differentiate PHEO from non-PHEO and ROC analysis was applied to evaluate the diagnostic value of the independent variate., Results: We found that the T2-weighted (T2W) signal intensity in patients with pheochromocytoma was higher than other adrenal tumors, with greatly significant (p < 0.001). T2W signal intensity ratio (T2W nodule-to-muscle SI ratio) was an independent risk factor for the differential diagnosis of adrenal PHEOs from non-PHEOs. This feature alone had 91.4% sensitivity and 81.5% specificity to rule out pheochromocytoma based on optimal threshold, with an area under the receiver operating characteristics curve (AUC‑ROC) of 0.910(95% C I: 0.833-0.987)., Conclusion: Our study confirms that T2W signal intensity ratio can differentiate PHEO from non-PHEO, among which the consequences of biochemical screening tests of catecholamines and/or catecholamine metabolites are positive., (© 2024. The Author(s).)

Motilin (MLN) is a peptide hormone originally isolated from the mucosa of the porcine intestine. Its orthologs have been identified in various vertebrates. Although MLN regulates gastrointestinal motility in tetrapods from amphibians to mammals, recent studies indicate that MLN is not involved in the regulation of isolated intestinal motility in zebrafish, at least in vitro. To determine the unknown function of MLN in teleosts, we examined the expression of MLN and the MLN receptor (MLNR) at the cellular level in Japanese medaka (Oryzias latipes). Quantitative PCR revealed that mln mRNA was limitedly expressed in the gut, whereas mlnr mRNA was not detected in the gut but was expressed in the brain and kidney. By in situ hybridization and immunohistochemistry, mlnr mRNA was detected in the dopaminergic neurons of the area postrema in the brain and the noradrenaline-producing cells in the interrenal gland of the kidney. Furthermore, we observed efferent projections of mlnr-expressing dopaminergic neurons in the lobus vagi (XL) and nucleus motorius nervi vagi (NXm) of the medulla oblongata by establishing a transgenic medaka expressing the enhanced green fluorescence protein driven by the mlnr promoter. The expression of dopamine receptor mRNAs in the XL and cholinergic neurons in NXm was confirmed by in situ hybridization. These results indicate novel sites of MLN activity other than the gastrointestinal tract. MLN may exert central and peripheral actions through the regulation of catecholamine release in medaka., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Beta-adrenergic receptors (βARs) are G protein-coupled receptors (GPCRs) that mediate catecholamine hormone-induced stress responses, such as elevation of heart rate. Besides those that are plasma membrane-bound, endomembrane βARs are also signaling competent. Dysregulation of βAR pathways underlies severe pathological conditions. Emerging evidence indicates pathological molecular signatures in deeper endomembrane βARs signaling, likely contributing to conditions such as cardiomyocyte hypertrophy and apoptosis. However, the lack of approaches to control endomembrane β1ARs has impeded linking signaling with pathology. Informed by the β1AR-catecholamine interactions, we engineered an efficient photolabile proligand (OptoIso) to trigger βAR signaling exclusively in endomembrane regions using blue light stimulation. Not only does OptoIso undergo blue light deprotection in seconds, but also efficiently enters cells and allows examination of G protein heterotrimer activation exclusively at endomembranes. OptoIso also allows optical activation of plasma membrane βAR signaling in selected single cells with native fidelity, which can be reversed by terminating blue light. Thus, OptoIso will be a valuable experimental tool to elicit spatial and temporal control of βAR signaling in user-defined endomembrane or plasma membrane regions in unmodified cells with native fidelity., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest concerning the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Previous studies have suggested that long-term β-blocker therapy before sepsis is associated with reduced mortality. Sepsis-associated coagulopathy (SAC) remains a common complication in patients with sepsis and is associated with increased mortality. Adrenergic pathways are involved in the regulation of the coagulation system. Pre-existing long-term β-blocker therapy may have potentially beneficial effects on SAC and has yet to be well characterized. We aimed to assess the potential association between pre-existing long-term β-blocker therapy and the outcomes of patients with SAC. Materials and Methods: This study retrospectively screened the clinical data of adult patients with SAC admitted to the Intensive Care Unit (ICU) and respiratory ICU between May 2020 and October 2022. Patients with SAC who took any β-blocker for at least one year were considered pre-existing long-term β-blocker therapy. All enrolled patients were followed up for 28 days or until death. Results: Among the 228 SAC patients, 48 received long-term β-blocker therapy before septic episodes. Pre-existing long-term β-blocker therapy was associated with reduced vasopressor requirements and a decreased 28-day mortality (log-rank test: p = 0.041). In particular, long-term β-blocker therapy was related to substantially lower D-dimer levels and a trend of improved activated partial thromboplastin time in patients with SAC during initial ICU admission. Multivariable regression analysis showed that long-term β-blocker therapy was significantly and independently associated with a 28-day mortality among patients with SAC (adjusted odds ratio, 0.55; 95% confidence interval, (0.32–0.94); p = 0.030). Conclusions: Pre-existing long-term β-blocker therapy might be associated with reduced vasopressor requirements and a decreased 28-day mortality among patients with SAC, providing evidence for the protective effect of β-blockers against SAC in managing sepsis.

While polydopamine (PDA) possesses the surface-independent adhesion property of mussel-binding proteins, significant differences exist between them. Particularly, PDA's short and rigid backbone differs from the long and flexible protein sequence of mussel-binding proteins. Given that adhesion relies on achieving a conformal contact with large surface coverage, PDA has drawbacks as an adhesive. In our study, we investigated the roles of each building block of PDA to build a better understanding of their binding mechanisms. Initially, we anticipated that catecholamine oligomers form specific binding with substrates. However, our study showed that the universal adhesion of PDA is initiated by the solubility limit of growing oligomers by forming agglomerates, complemented by multiple binding modes of catechol. Notably, in the absence of amines, poly(catechol) either remained in solution or formed minor suspensions without any surface coating, underscoring the essential role of amines in the adhesion process by facilitating insoluble aggregate formation. To substantiate our findings, we induced poly(catechol) aggregation using quaternized poly(4-vinylpyridine) (qPVP), leading to subsequent surface adhesion upon agglomerate formation.

Aims: Adequate animal models are necessary to understand human conditions, such as takotsubo syndrome (TS) characterized by the heart's transient regional wall motion abnormalities. This study aims to develop a reproducible, low-mortality TS model that closely mimics the human condition and addresses the limitations of existing models., Methods and Results: We conducted six experiments using 309 Sprague Dawley rats, each approximately 300 g and aged 7-8 weeks. Initially, we replicated an established model using intraperitoneal isoprenaline injections. Subsequent experiments varied the doses and infusion durations of intravenous isoprenaline and assessed the effects of sex, strain, and breeder on the development of reversible akinetic segments. High-resolution echocardiography monitored the regional wall motion over 30 days to correlate with histological changes. Increasing the isoprenaline dose and the infusion time significantly enhanced akinesia ( P < 0.01), resulting in pronounced apical ballooning observed in three-dimensional imaging. Akinesia peaked at 6 h post-infusion, with recovery observed at 24 h; most rats recovered from akinetic segments within 48-72 h. Optimizing the mode of administration, dose, and duration achieved a TS-like phenotype in 90% of cases, with a 16.7% mortality rate. Histological examinations confirmed that myocardial injury occurred, independent of apical ballooning., Conclusion: This study presents a refined TS model that reliably replicates the syndrome's key features, including morphological and electrocardiographic changes, demonstrating its transient nature with high fidelity and reduced mortality. The model's reproducibility, evidenced by consistent results across trials, suggests its potential for broader application pending further validation., Competing Interests: Conflict of interest: none declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Purpose: Vasovagal syncope (VVS) and psychogenic pseudosyncope (PPS) can be difficult to distinguish, given their similar clinical presentations. This study was conducted to explore the clinical value of catecholamine levels in the differential diagnosis of VVS and PPS in children., Methods: This retrospective case-control study was conducted with data from children with VVS and PPS who underwent head-up tilt tests (HUTTs) at the Children's Hospital of Hebei Province between March 2021 and March 2023. The data collected were baseline clinical characteristics, HUTT results, serum catecholamine levels in the supine and upright positions, and 24 h urinary catecholamine concentrations. These variables were compared between the VVS and PPS groups., Results: From 328 potentially eligible cases, 54 (16.46%) cases of VVS and 24 (7.32%) cases of PPS were included in the analysis. No significant difference in age, sex, body mass index, or syncope frequency was observed between the VVS and PPS groups. The main predisposing factors for syncope were body position changes in the VSS group (83.33%) and emotional changes in the PPS group (41.67%). The episode duration was significantly shorter in the VSS group than in the PPS group (4.01 ± 1.20 vs. 24.06 ± 5.56 min, p  < 0.05). The recovery time was also shorter in the VVS group than in the PPS group (1.91 ± 0.85 vs. 8.62 ± 2.55 min, p  < 0.05). Relative to patients with PPS, those with VVS had significantly higher serum epinephrine (EP) levels in the upright position [199.35 (102.88, 575.00) vs. 147.40 (103.55, 227.25), p  < 0.05] and lower serum epinephrine levels in the supine position [72.70 (42.92, 122.85) vs. 114.50 (66.57, 227.50), p  < 0.05]., Conclusions: Serum EP levels have potential value in the differential diagnosis of VVS and PPS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Wang, Ma, Jin, Li and Sun.)

In eutocic labor, the autonomic nervous system is dominated by the parasympathetic system, which ensures optimal blood flow to the uterus and placenta. This study is focused on the detection of the quantitative presence of catecholamine (C) neurofibers in the internal uterine orifice (IUO) and in the lower uterine segment (LUS) of the pregnant uterus, which could play a role in labor and delivery. A total of 102 women were enrolled before their submission to a scheduled cesarean section (CS); patients showed a singleton fetus in a cephalic presentation outside labor. During CS, surgeons sampled two serial consecutive full-thickness sections 5 mm in depth (including the myometrial layer) on the LUS and two randomly selected samples of 5 mm depth from the IUO of the cervix. All histological samples were studied to quantify the distribution of A nerve fibers. The authors demonstrated a significant and notably higher concentration of A fibers in the IUO (46 ± 4.8) than in the LUS (21 ± 2.6), showing that the pregnant cervix has a greater concentration of A neurofibers than the at-term LUS. Pregnant women's mechanosensitive pacemakers can operate normally when the body is in a physiological state, which permits normal uterine contractions and eutocic delivery. The increased frequency of C neurofibers in the cervix may influence the smooth muscle cell bundles' activation, which could cause an aberrant mechano-sensitive pacemaker activation-deactivation cycle. Stressful circumstances (anxiety, tension, fetal head position) cause the sympathetic nervous system to become more active, working through these nerve fibers in the gravid cervix. They might interfere with the mechano-sensitive pacemakers, slowing down the uterine contractions and cervix ripening, which could result in dystocic labor.