Sympathetic Neuronal Activation Triggers Myeloid Progenitor Proliferation and Differentiation.

There is a growing body of research on the neural control of immunity and inflammation. However, it is not known whether the nervous system can regulate the production of inflammatory myeloid cells from hematopoietic progenitor cells in disease conditions. Myeloid cell numbers in diabetic patients were strongly correlated with plasma concentrations of norepinephrine, suggesting the role of sympathetic neuronal activation in myeloid cell production. The spleens of diabetic patients and mice contained higher numbers of tyrosine hydroxylase (TH)-expressing leukocytes that produced catecholamines. Granulocyte macrophage progenitors (GMPs) expressed the ß2 adrenergic receptor, a target of catecholamines. Ablation of splenic sympathetic neuronal signaling using surgical, chemical, and genetic approaches diminished GMP proliferation and myeloid cell development. Finally, mice lacking TH-producing leukocytes had reduced GMP proliferation, resulting in diminished myelopoiesis. Taken together, our study demonstrates that catecholamines produced by leukocytes and sympathetic nerve termini promote GMP proliferation and myeloid cell development.

Natural photoredox catalysts promote light-driven lytic polysaccharide monooxygenase reactions and enzymatic turnover of biomass.

Lytic polysaccharide monooxygenases (LPMOs) catalyze oxidative cleavage of crystalline polysaccharides such as cellulose and chitin and are important for biomass conversion in the biosphere as well as in biorefineries. The target polysaccharides of LPMOs naturally occur in copolymeric structures such as plant cell walls and insect cuticles that are rich in phenolic compounds, which contribute rigidity and stiffness to these materials. Since these phenolics may be photoactive and since LPMO action depends on reducing equivalents, we hypothesized that LPMOs may enable light-driven biomass conversion. Here, we show that redox compounds naturally present in shed insect exoskeletons enable harvesting of light energy to drive LPMO reactions and thus biomass conversion. The primary underlying mechanism is that irradiation of exoskeletons with visible light leads to the generation of H2O2, which fuels LPMO peroxygenase reactions. Experiments with a cellulose model substrate show that the impact of light depends on both light and exoskeleton dosage and that light-driven LPMO activity is inhibited by a competing H2O2-consuming enzyme. Degradation experiments with the chitin-rich exoskeletons themselves show that solubilization of chitin by a chitin-active LPMO is promoted by light. The fact that LPMO reactions, and likely reactions catalyzed by other biomass-converting redox enzymes, are fueled by light-driven abiotic reactions in nature provides an enzyme-based explanation for the known impact of visible light on biomass conversion.

Spatial contextual recognition memory updating is modulated by dopamine release in the dorsal hippocampus from the locus coeruleus.

Detecting novelty is critical to consolidate declarative memories, such as spatial contextual recognition memory. It has been shown that stored memories, when retrieved, are susceptible to modification, incorporating new information through an updating process. Catecholamine release in the hippocampal CA1 region consolidates an object location memory (OLM). This work hypothesized that spatial contextual memory updating could be changed by decreasing catecholamine release in the hippocampal CA1 terminals from the locus coeruleus (LC). In a mouse model expressing Cre-recombinase under the control of the tyrosine hydroxylase (TH) promoter, memory updating was impaired by photoinhibition of the CA1 catecholaminergic terminals from the LC (LC-CA1) but not from the ventral tegmental area (VTA-CA1). In vivo microdialysis confirmed that the extracellular concentration of both dopamine (DA) and noradrenaline (NA) decreased after photoinhibition of the LC-CA1 terminals (but not VTA-CA1) during the OLM update session. Furthermore, DA D1/D5 and beta-adrenergic receptor antagonists disrupted behavior, but only the former impaired memory updating. Finally, photoinhibition of LC-CA1 terminals suppressed long-term potentiation (LTP) induction in Schaffer's collaterals as a plausible mechanism for memory updating. These data will help understand the underpinning mechanisms of DA in spatial contextual memory updating.

An 840 kb distant upstream enhancer is a crucial regulator of catecholamine-dependent expression of the Bdnf gene in astrocytes.

Brain-derived neurotrophic factor (BDNF) plays a fundamental role in the developing and adult nervous system, contributing to neuronal survival, differentiation, and synaptic plasticity. Dysregulation of BDNF synthesis, secretion or signaling has been associated with many neurodevelopmental, neuropsychiatric, and neurodegenerative disorders. Although the transcriptional regulation of the Bdnf gene has been extensively studied in neurons, less is known about the regulation and function of BDNF in non-neuronal cells. The most abundant type of non-neuronal cells in the brain, astrocytes, express BDNF in response to catecholamines. However, genetic elements responsible for this regulation have not been identified. Here, we investigated four potential Bdnf enhancer regions and based on reporter gene assays, CRISPR/Cas9 engineering and CAPTURE-3C-sequencing we conclude that a region 840 kb upstream of the Bdnf gene regulates catecholamine-dependent expression of Bdnf in rodent astrocytes. We also provide evidence that this regulation is mediated by CREB and AP1 family transcription factors. This is the first report of an enhancer coordinating the transcription of Bdnf gene in non-neuronal cells.

Role of epigenetic regulation on catecholamine synthesis in pheochromocytoma and paraganglioma.

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

Plasma epinephrine and norepinephrine responses to extreme heat exposures in young and older adults.

Hyperthermia is known as a hyperadrenergic state, yet there is a lack of data on the sympathetic responses to ambient heat stress in humans. Therefore, we investigated the plasma epinephrine and norepinephrine concentrations of healthy young and older adults exposed to 3-hours of very-hot and dry and hot-humid heat, both with accompanying activities of daily living. We hypothesized that older adults, compared to young adults, would have augmented increases in epinephrine and norepinephrine concentrations secondary to increased thermal strain. Young (n=20) and older (n=18) participants underwent two 3-hour heat exposures on different days: very hot and dry (47°C and 15% RH) and hot and humid (41°C and 40% RH). To mimic heat generation comparable to activities of daily living, participants performed seven 5-minute bouts of light cycling (~3 METS) dispersed throughout the heat exposure. We measured plasma concentrations of epinephrine and norepinephrine at baseline, end, and 2hrs post-heat exposure. There was a group-wide increase in epinephrine from baseline to the end of the heat exposure (Δ19±27 pg/mL; p<0.001) in the hot and humid but not the very hot and dry condition (Δ6±19 pg/mL; p=0. 10 ). There were group-wide decreases in norepinephrine concentrations from baseline to the end of the heat exposure in both the very hot and dry (Δ-131±169 pg/mL; p<0.001) and the hot and humid (Δ-138±157 pg/mL; p<0.001) conditions, with both returning to near baseline at 2hrs post-exposure. These data suggest that ambient heating with accompanying bouts of light intermittent exercise may lead to decreases in circulating concentrations of norepinephrine.

The expression of Catsup in the hindgut is essential for zinc homeostasis in Drosophila melanogaster.

Zinc excretion is crucial for zinc homeostasis. However, the mechanism of zinc excretion has not been well characterized. Zinc homeostasis in Drosophila seems well conserved to mammals. In this study, we screened all members of the zinc transporters ZnT (SLC30) and Zip (SLC39) for their potential roles in Drosophila hindgut, an insect organ that belongs to the excretory system. The results indicated that Catecholamines up (Catsup, CG10449), a ZIP member localized to the Golgi, is responsible for zinc homeostasis in the hindgut of Drosophila hindgut-specific knockdown of Catsup leads to a developmental arrest in the larval stage, which could be rescued well by human ZIP7. Further study suggested that Catsup RNAi in the hindgut reduced zinc levels in the excretory system (containing the Malpighian tubule and hindgut) but exhibited systemic zinc overload. Besides, more calculi were observed in the Malpighian tubules of Catsup RNAi flies. The developmental arrest and calculi in the Malpighian tubules of hindgut-specific Catsup RNAi flies could be rescued by dietary zinc restriction but hypersensitivity to zinc. These results will help us understand the fundamental process of zinc excretion in higher eukaryotes.

Consensus Paper: Cerebellum and Reward.

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

Impact of L-theanine and L-tyrosine on markers of stress and cognitive performance in response to a virtual reality based active shooter training drill.

Ingestion of L-theanine and L-tyrosine has been shown to reduce salivary stress biomarkers and improve aspects of cognitive performance in response to stress. However, there have been no studies to concurrently examine the impact of both L-theanine and L-tyrosine ingestion during a mental stress challenge (MSC) involving a brief cognitive challenge and a virtual reality based active shooter training drill. Thus, the purpose of this study was to determine the impact of ingestion of L-theanine and L-tyrosine on markers of stress and cognitive performance in response to a virtual reality active shooter drill and cognitive challenge. The cognitive challenge involved a Stroop challenge and mental arithmetic. Eighty subjects (age = 21 ± 2.6 yrs; male = 46; female = 34) were randomly assigned L-tyrosine (n = 28; 2000 mg), L-theanine (n = 25; 200 mg), or placebo (n = 27) prior to MSC exposure. Saliva samples, state-anxiety inventory (SAI) scales, and heart rate (HR) were collected before and after exposure to the MSC. Saliva was analyzed for stress markers α-amylase (sAA) and secretory immunoglobulin A (SIgA). The MSC resulted in significant increases in sAA, SIgA, HR, and SAI. Ingestion of L-theanine and L-tyrosine did not impact markers of stress. However, the L-tyrosine treatment demonstrated significantly lower missed responses compared to the placebo treatment group during the Stroop challenge. These data demonstrate that ingestion of L-theanine or L-tyrosine does not impact markers of stress in response to a MSC but may impact cognitive performance. This study was pre-registered as a clinical trial ("Impact of supplements on stress markers": NCT05592561).

Effect of zamicastat on blood pressure and heart rate response to cold pressor test: A double-blind, randomized, placebo-controlled study in healthy subjects.

AIMS: Dopamine beta-hydroxylase (DßH) 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 DßH 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 DßH 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.

Blasting off: persistent hypertension in a child with neuroblastoma.

Hypertension in children with neuroblastoma is uncommon and can be difficult to control due to the potential for multiple underlying causes. We present the case of a pediatric patient with high-grade neuroblastoma which was complicated by hypertensive emergency. The patient had imaging suggestive of renal artery compression, as well as significantly elevated normetaphrine levels. Multiple anti-hypertensive agents, including an angiotensin converting enzyme inhibitor, α- and ß-adrenergic receptor blockers, and a tyrosine hydroxylase inhibitor, were initiated prior to tumor excision. While her blood pressure improved during the post-operative period, she continued to require multiple antihypertensive medications due to residual tumor burden. In this report, we highlight the importance of careful, multidisciplinary management to avoid peri-operative complications in patients with catecholamine-producing tumors.

Signaling Ligand Heterogeneities in the Peduncle Complex of the Cephalopod Mollusc Octopus bimaculoides.

INTRODUCTION: The octopus peduncle complex is an agglomeration of neural structures with remarkably diverse functional roles. The complex rests on the optic tract, between the optic lobe and the central brain, and comprises the peduncle lobe proper, the olfactory lobe, and the optic gland. The peduncle lobe regulates visuomotor behaviors, the optic glands control sexual maturation and maternal death, and the olfactory lobe is thought to receive input from the olfactory organ. Recent transcriptomic and metabolomic studies have identified candidate peptide and steroid ligands in the Octopus bimaculoides optic gland. METHODS: With gene expression for these ligands and their biosynthetic enzymes, we show that optic gland neurochemistry extends beyond the traditional optic gland secretory tissue and into lobular territories. RESULTS: A key finding is that the classically defined olfactory lobe is itself a heterogeneous territory and includes steroidogenic territories that overlap with cells expressing molluscan neuropeptides and the synthetic enzyme dopamine beta-hydroxylase. CONCLUSION: Our study reveals the neurochemical landscape of the octopus peduncle complex, highlighting the unexpected overlap between traditionally defined regions.

Infiltrating macrophages amplify doxorubicin-induced cardiac damage: role of catecholamines.

BACKGROUND: The functional contribution of non-myocyte cardiac cells, such as inflammatory cells, in the setup of heart failure in response to doxorubicin (Dox) is recently becoming of growing interest. OBJECTIVES: The study aims to evaluate the role of macrophages in cardiac damage elicited by Dox treatment. METHODS: C57BL/6 mice were treated with one intraperitoneal injection of Dox (20 mg/kg) and followed up for 5 days by cardiac ultrasounds (CUS), histological, and flow cytometry evaluations. We also tested the impact of Dox in macrophage-depleted mice. Rat cardiomyoblasts were directly treated with Dox (D-Dox) or with a conditioned medium from cultured murine macrophages treated with Dox (M-Dox). RESULTS: In response to Dox, macrophage infiltration preceded cardiac damage. Macrophage depletion prevents Dox-induced damage, suggesting a key role of these cells in promoting cardiotoxicity. To evaluate the crosstalk between macrophages and cardiac cells in response to DOX, we compared the effects of D-Dox and M-Dox in vitro. Cell vitality was lower in cardiomyoblasts and apoptosis was higher in response to M-Dox compared with D-Dox. These events were linked to p53-induced mitochondria morphology, function, and autophagy alterations. We identify a mechanistic role of catecholamines released by Dox-activated macrophages that lead to mitochondrial apoptosis of cardiac cells through ß-AR stimulation. CONCLUSIONS: Our data indicate that crosstalk between macrophages and cardiac cells participates in cardiac damage in response to Dox.

Effect of propranolol on temporomandibular joint pain in repeatedly stressed rats.

Stress substantially increases the risk of developing painful temporomandibular disorders (TMDs) by influencing the release of endogenous catecholamines. Propranolol, an antagonist of ß-adrenergic receptors, has shown potential in alleviating TMD-associated pain, particularly when the level of catecholamines is elevated. The aim of this study was to explore whether intra-articular propranolol administration is effective in diminishing temporomandibular joint (TMJ) pain during repeated stress situations. Additionally, we investigated the effect of repeated stress on the expression of genes encoding ß-adrenoceptors in the trigeminal ganglion. In the present study, rats were exposed to a stress protocol induced by sound, then to the administration of formalin in the TMJ (to elicit a nociceptive response), followed immediately afterward by different doses of propranolol, after which the analgesic response to propranolol was evaluated. We also assessed the levels of beta-1 and beta-2 adrenergic receptor mRNAs (Adrb1 and Adrb2, respectively) using reverse transcription-quantitative PCR (RT-qPCR). Our findings revealed that propranolol administration reduces formalin-induced TMJ nociception more effectively in stressed rats than in non-stressed rats. Furthermore, repeated stress decreases the expression of the Adrb2 gene within the trigeminal ganglion. The findings of this study are noteworthy as they suggest that individuals with a chronic stress history might find potential benefits from ß-blockers in TMD treatment.

Preparation of branched polyethyleneimine-assisted boronic acid-functionalized magnetic MXene for the enrichment of catecholamines in urine samples.

Herein, a magnetic borate-functionalized MXene composite with multiple boronic affinity sites was fabricated by embedding Fe3 O4 nanoparticles with 4-formylphenylboronic acid functionalized Ti3 C2 Tx nanosheets and served as sorbent for the simultaneous extraction of catecholamines (CAs) in urine samples. The morphology and structure of the magnetic materials were investigated using scanning microscopy, vibrating sample magnetometer, X-ray photoelectron spectrometer, and X-ray diffraction. The introduction of polyethyleneimine can amplify the bonded boronic acid groups, thereby effectively improving the adsorption capacities for CAs based on the multiple interactions of boronic affinity, hydrogen bonding, and metal coordination. The adsorption performance was investigated using the kinetics and isotherms models, and the main parameters that influence the extraction efficiency were optimized. Under the most favorable magnetic solid-phase extraction condition, a sensitive method for the analysis of CAs in urine samples was developed by combining magnetic solid-phase extraction conditions with high-performance liquid chromatography detection. The findings illustrated that the proposed approach possessed a wide linearity range of 0.05-250 ng/mL with an acceptable correlation coefficient (R2  ≥ 0.9984) and detection limits of 0.010-0.015 ng/mL for the target CAs. The research not only provides a notable composite with multiple boronic affinity sites but also offers an effective and feasible measure for the detection of CAs in biological samples.

ß-adrenergic stimulation after rewarming does not mitigate hypothermia-induced contractile dysfunction in rat cardiomyocytes.

Victims of severe accidental hypothermia are frequently treated with catecholamines to counteract the hemodynamic instability associated with hypothermia-induced cardiac contractile dysfunction. However, we previously reported that the inotropic effects of epinephrine are diminished after hypothermia and rewarming (H/R) in an intact animal model. Thus, the goal of this study was to investigate the effects of Epi treatment on excitation-contraction coupling in isolated rat cardiomyocytes after H/R. In adult male rats, cardiomyocytes isolated from the left ventricle were electrically stimulated at 0.5 Hz and evoked cytosolic [Ca2+] and contractile responses (sarcomere length shortening) were measured. In initial experiments, the effects of varying concentrations of epinephrine on evoked cytosolic [Ca2+] and contractile responses at 37 °C were measured. In a second series of experiments, cardiomyocytes were cooled from 37 °C to 15 °C, maintained at 15 °C for 2 h, then rewarmed to 37 °C (H/R protocol). Immediately after rewarming, the effects of epinephrine treatment on evoked cytosolic [Ca2+] and contractile responses of cardiomyocytes were determined. At 37 °C, epinephrine treatment increased both cytosolic [Ca2+] and contractile responses of cardiomyocytes in a concentration-dependent manner peaking at 25-50 nM. The evoked contractile response of cardiomyocytes after H/R was reduced while the cytosolic [Ca2+] response was slightly elevated. The diminished contractile response of cardiomyocytes after H/R was not mitigated by epinephrine (25 nM) and epinephrine treatment reduced the exponential time decay constant (Tau), but did not increase the cytosolic [Ca2+] response. We conclude that epinephrine treatment does not mitigate H/R-induced contractile dysfunction in cardiomyocytes.

Effects of noise exposure on stress hormone changes during task performance in young Korean men: quasi-experimental study.

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

Norepinephrine versus epinephrine for hemodynamic support in post-cardiac arrest shock: A systematic review.

PURPOSE: The preferred vasopressor in post-cardiac arrest shock has not been established with robust clinical outcomes data. Our goal was to perform a systematic review and meta-analysis comparing rates of in-hospital mortality, refractory shock, and hemodynamic parameters in post-cardiac arrest patients who received either norepinephrine or epinephrine as primary vasopressor support. METHODS: We conducted a search of PubMed, Cochrane Library, and CINAHL from 2000 to 2022. Included studies were prospective, retrospective, or published abstracts comparing norepinephrine and epinephrine in adults with post-cardiac arrest shock or with cardiogenic shock and extractable post-cardiac arrest data. The primary outcome of interest was in-hospital mortality. Other outcomes included incidence of arrhythmias or refractory shock. RESULTS: The database search returned 2646 studies. Two studies involving 853 participants were included in the systematic review. The proposed meta-analysis was deferred due to low yield. Crude incidence of in-hospital mortality was numerically higher in the epinephrine group compared with norepinephrine in both studies, but only statistically significant in one. Risk of bias was moderate to severe for in-hospital mortality. Additional outcomes were reported differently between studies, minimizing direct comparison. CONCLUSION: The vasopressor with the best mortality and hemodynamic outcomes in post-cardiac arrest shock remains unclear. Randomized studies are crucial to remedy this.

An LC-MS/MS method for the simultaneous determination of 6-cyanodopamine, 6-nitrodopamine, 6-nitrodopa, 6-nitroadrenaline and 6-bromodopamine in human plasma and its clinical application in patients with chronic kidney disease.

The aim of this study was to develop a high-performance liquid chromatography-tandem mass spectrometry method for the determination of 6-cyanodopamine, 6-nitrodopamine, 6-nitrodopa, 6-nitroadrenaline and 6-bromodopamine in human plasma samples. Strata-X 33 µm solid-phase extraction cartridges were used for the extraction of the catecholamines from human plasma samples. The catecholamines were separated in a 150 × 3 mm Shim-pack GIST C18-AQ column with 3 µm particle size, placed in an oven at 40°C and perfused with 82% mobile phase A (acetonitrile-H2O; 90:10, v/v) + 0.4% acetic acid and 18% mobile phase B (deionized H2O) + 0.2% formic acid at a flow rate of 340 µl/min in isocratic mode. The injected volume was 4 µl and the run lasted 4 min. The method was linear from 0.1 to 20 ng/ml and the lower limit of quantification was 0.1 ng/ml for all analytes. The method was applied to evaluate the plasma levels of catecholamines in plasma of patients with chronic kidney disease and allowed the detection for the first time of circulating levels of the novel catecholamines 6-bromodopamine and 6-cyanodopamine.

[Paragangliomas of the head and neck]. / Paragangliome im Kopf-Hals-Bereich.

Paragangliomas represent a heterogeneous group of rare neuroendocrine tumors with marked variability in symptoms and disease course. Due to the close proximity to neurovascular structures, paragangliomas of the head and neck region can cause a variety of symptoms. To this day, there are no reliable prognostic factors that can predict a potentially malignant course. All patients with newly diagnosed paragangliomas should undergo an early diagnostic workup and regular follow-up examinations in specialized centers. While radical resection was previously regarded as standard treatment for paragangliomas, radiotherapy and active surveillance (watch-and-scan strategy) have become equally important over the years. Low-threshold techniques for molecular pathology analysis of the mutation-specific behavior of paragangliomas are nowadays available.