In a Canine Model of Septic Shock, Cardiomyopathy Occurs Independent of Catecholamine Surges and Cardiac Microvascular Ischemia.

BACKGROUND: High levels of catecholamines are cardiotoxic and associated with stress-induced cardiomyopathies. Using a septic shock model that reproduces the reversible cardiomyopathy seen over 10 days associated with human septic shock, we investigated the effects of catecholamines on microcirculatory perfusion and cardiac dysfunction. METHODS AND RESULTS: Purpose-bred beagles received intrabronchial Staphylococcus aureus (n=30) or saline (n=6). The septic animals were than randomized to epinephrine (1 µg/kg per minute, n=15) or saline (n=15) infusions from 4 to 44 hours. Serial cardiac magnetic resonance imaging, catecholamine levels, and troponins were collected over 92 hours. Serial adenosine-stress perfusion cardiac magnetic resonance imaging was performed on septic animals randomized to receive saline (n=8 out of 15) or epinephrine (n=8 out of 15). High-dose sedation was given to suppress endogenous catecholamine release. Despite catecholamine levels largely remaining within the normal range throughout, by 48 hours, septic animals receiving saline versus nonseptic animals still developed significant worsening of left ventricular ejection fraction, circumferential strain, and ventricular-aortic coupling. In septic animals that received epinephrine versus saline infusions, plasma epinephrine levels increased 800-fold, but epinephrine produced no significant further worsening of left ventricular ejection fraction, circumferential strain, or ventricular-aortic coupling. Septic animals receiving saline had a significant increase in microcirculatory reserve without troponin elevations. Septic animals receiving epinephrine had decreased edema, blunted microcirculatory perfusion, and elevated troponin levels that persisted for hours after the epinephrine infusion stopped. CONCLUSIONS: Cardiac dysfunction during sepsis is not primarily due to elevated endogenous or exogenous catecholamines nor due to decreased microvascular perfusion-induced ischemia. However, epinephrine itself has potentially harmful long-lasting ischemic effects during sepsis including impaired cardiac microvascular perfusion that persists after stopping the infusion.

Roles and Mechanisms of Dopamine Receptor Signaling in Catecholamine Excess Induced Endothelial Dysfunctions.

Endothelial dysfunction may contribute to pathogenesis of Takotsubo cardiomyopathy, but mechanism underlying endothelial dysfunction in the setting of catecholamine excess has not been clarified. The study reports that D1/D5 dopamine receptor signaling and small conductance calcium-activated potassium channels contribute to high concentration catecholamine induced endothelial cell dysfunction. For mimicking catecholamine excess, 100 µM epinephrine (Epi) was used to treat human cardiac microvascular endothelial cells. Patch clamp, FACS, ELISA, PCR, western blot and immunostaining analyses were performed in the study. Epi enhanced small conductance calcium-activated potassium channel current (ISK1-3) without influencing the channel expression and the effect was attenuated by D1/D5 receptor blocker. D1/D5 agonists mimicked the Epi effect, suggesting involvement of D1/D5 receptors in Epi effects. The enhancement of ISK1-3 caused by D1/D5 activation involved roles of PKA, ROS and NADPH oxidases. Activation of D1/D5 and SK1-3 channels caused a hyperpolarization, reduced NO production and increased ROS production. The NO reduction was membrane potential independent, while ROS production was increased by the hyperpolarization. ROS (H2O2) suppressed NO production. The study demonstrates that high concentration catecholamine can activate D1/D5 and SK1-3 channels through NADPH-ROS and PKA signaling and reduce NO production, which may facilitate vasoconstriction in the setting of catecholamine excess.

A New BODIPY-Based Receptor for the Fluorescent Sensing of Catecholamines.

The human body synthesizes catecholamine neurotransmitters, such as dopamine and noradrenaline. Monitoring the levels of these molecules is crucial for the prevention of important diseases, such as Alzheimer's, schizophrenia, Parkinson's, Huntington's, attention-deficit hyperactivity disorder, and paragangliomas. Here, we have synthesized, characterized, and functionalized the BODIPY core with picolylamine (BDPy-pico) in order to create a sensor capable of detecting these biomarkers. The sensing properties of the BDPy-pico probe in solution were studied using fluorescence titrations and supported by DFT studies. Catecholamine sensing was also performed in the solid state by a simple strip test, using an optical fiber as the detector of emissions. In addition, the selectivity and recovery of the sensor were assessed, suggesting the possibility of using this receptor to detect dopamine and norepinephrine in human saliva.

Catecholaminergic Modulation of Metacontrol Is Reflected by Changes in Aperiodic EEG Activity.

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

Novel Schiff's base-assisted synthesis of metal-ligand nanostructures for multi-functional applications: Detection of catecholamines/antibiotics, removal of tetracycline, and antifungal treatment against plant pathogens.

The development of nanozymes (NZ) for the simultaneous detection of multiple target chemicals is gaining paramount attention in the field of food and health sciences, and waste management industries. Nanozymes (NZ) effectively compensate for the environmental vulnerability of natural enzymes. Considering the development gap of NZ with diverse applications, we synthesized versatile Schiff's base ligands following a facile route and readily available starting reagents (glutaraldehyde, aminopyridines). DPDI, one of the synthesized ligands, readily reacted with transition metal ions (Cu+2, Ag+1, Zn+2 in specific) under ambient conditions, yielding the corresponding nanoparticles/MOF. The structures of ligands and their products were confirmed using various analytical techniques. The enzymatic efficacy of DPDI-Cu (km 0.25 mM=, Vmax = 10.75 µM/sec) surpassed Tremetese versicolor laccase efficacy (km 0. 5 mM=, Vmax = 2.15 µM/sec). Additionally, DPDI-Cu proved resilient to changing pH, temperature, ionic strength, organic solvent, and storage time compared to laccase and provided reusability. DPDI-Cu proved promising for colorimetric detection of dopamine, epinephrine, catechol, tetracycline, and quercetin. The mechanism of oxidative detection of TC was studied through LC/MS analysis. DPDI-Cu-bentonite composite efficiently adsorbed tetracycline with maximum Langmuir adsorption of 208 mg/g. Moreover, DPDI/Cu and DPDI-Ag nanoparticles possessed antifungal activity exhibiting a minimum inhibitory concentration of 400 µg/mL and 3.12 µg/mL against Aspergillus flavus. Florescent dye tracking and SEM/TEM analysis confirmed that DPDI-Ag caused disruption of the plasma membrane and triggered ROS generation and apoptosis-like death in fungal cells. The DPDI-Ag coating treatment of wheat seeds confirmed the non-phytotoxicity of Ag-NPs.

Catecholamines-based myocardial injury after acute ischemic stroke and effects of Naoxintong capsule therapy.

BACKGROUND: Myocardial injury (MI) after acute ischemic stroke (AIS) poses a significant threat to patient prognosis. However, effective intervention strategies are currently lacking. PURPOSE: To elucidate the mechanism of MI after AIS and effects of Naoxintong capsule (NXT) therapy. METHOD: In vivo, after a rat model of middle cerebral artery occlusion (MCAO)-induced MI was established and assessed. NXT was administered prophylactically to evaluate its pharmacodynamic effects and mechanisms. In vitro, a noradrenaline (NA)-induced damage cell model was constructed. Subsequently, the NXT was applied to the cell models to examine its cardioprotective effects and potential mechanisms. RESULTS: The in vivo findings revealed that following MCAO, there was a notable upregulation of TH expression in the rat brain, which subsequently triggered an increase in serum levels of various biomarkers, including AD, NA, AST, cTnT, CK-MB, and NT-proBNP. Histological analysis employing H&E staining and TUNEL assay disclosed significant pathological alterations and an escalation in apoptotic activity within the myocardial tissue. The myocardial tissue exhibited elevated levels of MDA alongside diminished CAT activity. Additionally, a marked increase in the Bax/Bcl-2 ratio, Cytochrome C release, and Caspase-3 activation was observed, all of which are indicative of heightened apoptotic activity. Administration of the NXT intervention successfully attenuated TH expression in the brains of rats subjected to MCAO, consequently leading to a reduction in circulating levels of catecholamines (CAs). NXT also exhibited significant efficacy at ameliorating cardiac oxidative stress and reducing apoptosis. In vitro, stimulation with NA led to an increase in ROS levels and calcium ion concentration in H9c2 cardiomyocytes. However, the administration of NXT has been found to effectively alleviate these adverse effects, thereby protecting H9c2 cardiomyocytes from the deleterious consequences of oxidative stress and calcium dyshomeostasis. CONCLUSION: Overall, this study has demonstrated that increased CAs synthesis in the brain after AIS in experimental rats led to a surge in circulating CAs, ultimately leading to MI. NXT can alleviate MI due to cerebral ischemia by increasing improving brain catecholamine synthesis, cardiac oxidative stress, and apoptosis.

Effect of sex on chronic stress induced alterations in hindbrain catecholaminergic system and autonomic dysfunction resulting in gastrointestinal dysmotility.

It has been reported that the clinical symptoms of functional dyspepsia (FD) exacerbate upon stress while the gender-related factors have been incompletely understood. This study aims to investigate the role of sex in chronic heterotypic stress (CHS)-induced autonomic and gastric motor dysfunction. For CHS, the rats were exposed to the combination of different stressors for 7 consecutive days. Subsequently, electrocardiography was recorded in anesthetized rats to evaluate heart rate variability (HRV) for the determination of autonomic outflow and sympathovagal balance. Solid gastric emptying (GE) was measured in control and CHS-loaded male and female rats. The immunoreactivities of catecholaminergic cell marker tyrosine hydroxylase (TH), choline acetyltransferase (ChAT), corticotropin releasing factor (CRF), and estrogen receptor (ER-α/ß) were evaluated in medullary and pontine brainstem sections by immunohistochemistry. Compared with the controls, CHS significantly delayed GE in males but not in females. There was no significant sex-related difference in parasympathetic indicator HF under either control or CHS conditions. Sympathetic indicator LF was significantly higher in control females compared to the males. The higher sympathetic output in females was found to be attenuated upon CHS; in contrast, the elevated sympathetic output was detected in CHS-loaded males. No sex- or stress-related effect was observed on ChAT immunoreactivity in the dorsal motor nucleus of N.vagus (DMV). In males, greater number of TH-ir cells was observed in the caudal locus coeruleus (LC), while they were more densely detected in the rostral LC of females. Regardless of sex, CHS elevated immunoreactivity of TH throughout the LC. Under basal conditions, greater number of TH-ir cells was detected in the rostral ventrolateral medulla (RVLM) of females. In contrast, CHS remarkably increased the number of TH-ir cells in the RVLM of males which was found to be decreased in females. There was no sex-related alteration in TH immunoreactivity in the nucleus tractus solitarius (NTS) of control rats, while CHS affected both sexes in a similar manner. Compared with females, CRF immunoreactivity was prominently observed in control males, while both of which were stimulated by CHS. ER-α/ß was found to be co-expressed with TH in the NTS and LC which exhibit no alteration related to either sex or stress status. These results indicate a sexual dimorphism in the catecholaminergic and the CRF system in brainstem which might be involved in the CHS-induced autonomic and visceral dysfunction occurred in males.

Vagal predominance correlates with mood state changes of winter-over expeditioners during prolonged Antarctic residence.

OBJECTIVE: Winter-over expeditioners in Antarctica are challenged by various environmental and psycho-social stress factors, which may induce psychophysiological changes. The autonomic nervous system (ANS) plays a crucial role in the adaptation process under stress. However, the relationship between ANS activity and the mood states of expeditioners remains largely unexplored. This study aims to uncover the pattern of ANS adjustment under extreme Antarctic environments and provide new insights into the correlations between ANS activity and mood state changes, which may provide scientific data for medical interventions. METHODS: Fourteen expeditioners at Zhongshan Station participated in this study. The study was conducted during four representative periods: pre-Antarctica, Antarctica-1 (pre-winter), Antarctica-2 (winter), and Antarctica-3 (summer). The heart rate variability (HRV) of the expeditioners was continuously measured for 24 hours to evaluate ANS activity. Plasma levels of catecholamines were tested by ELISA. Mood states were assessed by the Profile of Mood States (POMS) scale. RESULTS: HRV analysis showed a disturbance of ANS during winter and summer periods. For frequency domain parameters, very low frequency (VLF), low frequency (LF), high frequency (HF), and total power (TP) significantly increased during the second half of the mission. Especially, LF/HF ratio decreased during summer, indicating the predominance of vagal tone. Results of the time domain analysis showed increased heart rate variability during the austral winter and summer. Plasma epinephrine (E) significantly increased during residence in Antarctica. Compared with pre-Antarctica, the vigor, depression, and anger scores of the expeditioners decreased significantly during the austral summer. Notably, the depression score showed a moderate positive correlation with LF/HF, while weak negative correlations with other HRV indicators, including TP, VLF, and LF. Anger score showed a moderate positive correlation with LF/HF and weak negative correlations with the average normal-to-normal (NN) interval, and the root mean square of differences between adjacent RR intervals (RMSSD). Plasma E level weakly correlated with the average NN interval. CONCLUSION: Prolonged residence in Antarctica increased the ANS activities and shifted the cardiac autonomic modulation towards vagal predominance. The alteration of HRV correlated with mood states and plasma epinephrine levels.

Diagnostic performance of magnetic resonance imaging features to differentiate adrenal pheochromocytoma from adrenal tumors with positive biochemical testing results.

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 (AUC­ROC) 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.

Pharmacological Elevation of Catecholamine Levels Improves Perceptual Decisions, But Not Metacognitive Insight.

Perceptual decisions are often accompanied by a feeling of decision confidence. Where the parietal cortex is known for its crucial role in shaping such perceptual decisions, metacognitive evaluations are thought to additionally rely on the (pre)frontal cortex. Because of this supposed neural differentiation between these processes, perceptual and metacognitive decisions may be divergently affected by changes in internal (e.g., attention, arousal) and external (e.g., task and environmental demands) factors. Although intriguing, causal evidence for this hypothesis remains scarce. Here, we investigated the causal effect of two neuromodulatory systems on behavioral and neural measures of perceptual and metacognitive decision-making. Specifically, we pharmacologically elevated levels of catecholamines (with atomoxetine) and acetylcholine (with donepezil) in healthy adult human participants performing a visual discrimination task in which we gauged decision confidence, while electroencephalography was measured. Where cholinergic effects were not robust, catecholaminergic enhancement improved perceptual sensitivity, while at the same time leaving metacognitive sensitivity unaffected. Neurally, catecholaminergic elevation did not affect sensory representations of task-relevant visual stimuli but instead enhanced well-known decision signals measured over the centroparietal cortex, reflecting the accumulation of sensory evidence over time. Crucially, catecholaminergic enhancement concurrently impoverished neural markers measured over the frontal cortex linked to the formation of metacognitive evaluations. Enhanced catecholaminergic neuromodulation thus improves perceptual but not metacognitive decision-making.

Localization of Catecholaminergic Neurofibers in Pregnant Cervix as a Possible Myometrial Pacemaker.

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.

Association between serum catecholamine levels and VNTR polymorphism in the promoter region of the monoamine oxidase A gene in forensic autopsy cases.

Monoamine oxidase A (MAOA) catalyzes oxidative deamination of catecholamines. A functional variable number tandem repeat (VNTR) polymorphism in the promoter region of the MAOA gene has been previously reported. In the present study, we measured serum adrenaline (Adr), noradrenaline (Nad), and dopamine (DA) levels in 90 male and 34 female Japanese autopsy cases in which amphetamines or psychotropic drugs were not detected.We examined the frequencies of MAOA-uVNTR alleles in these cases and investigated the effects of the MAOA-uVNTR polymorphism on serum Adr, Nad, and DA levels. Evaluation indicated no significant association between MAOA-uVNTR polymorphism and serum Adr, Nad, or DA levels in males, although a significant association between MAOA-uVNTR polymorphism and serum Adr and DA levels were observed in females. Females with the 3/3 genotype had higher serum Adr and DA levels than those with a 4-repeat allele (3/4 and 4/4 genotypes) (p = 0.048 and 0.020, respectively). There was no significant association between MAOA-uVNTR polymorphism and serum Nad levels in females. The present study indicates that MAOA-uVNTR polymorphism influences serum Adr and DA levels only in females.

Propranolol Alleviates Cardiac Injury After Acute Catecholamine Infusion Through p38-MAPK Pathways.

ABSTRACT: Hypercatecholaminergic conditions are known to cause heart failure and cardiac fibrosis when severe. Although previous investigations have studied the effects of beta-blockade in experimental models of catecholaminergic states, the detailed benefits of beta-blockade in more realistic models of hyper-adrenergic states were less clear. In this study, we examined acute cardiac changes in rats with hyperacute catecholamine-induced heart failure with and without propranolol treatment. Male Sprague-Dawley rats (n = 12) underwent a 6-hour infusion of epinephrine and norepinephrine alone, with an additional propranolol bolus (1 mg/kg) at hour 1 (n = 6). Cardiac tissues were examined after 6 hours. Cardiac immunohistochemistry revealed significantly decreased expression of phosphorylated p-38 (left ventricle, P = 0.021; right ventricle, P = 0.021), with upregulation of reactive oxidative species and other profibrosis proteins, after catecholamine infusion alone. After 1 propranolol 1 mg/kg bolus, the levels of phosphorylated-p38 returned to levels comparable with sham (left ventricle, P = 0.021; right ventricle, P = 0.043), with additional findings including downregulation of the apoptotic pathway and profibrotic proteins. We conclude that catecholamine-induced heart failure exerts damage through the p-38 mitogen-activated protein kinase pathway and demonstrates profibrotic changes mediated by matrix metalloproteinase 9, alpha-smooth muscle actin, and fibroblast growth factor 23. Changes in these pathways attenuated acute catecholamine-induced heart failure after propranolol bolus 1 mg/kg. We conclude that propranolol bolus at 1 mg/kg is able to mediate the effects of catecholamine excess through the p-38 mitogen-activated protein kinase pathway, profibrosis, and extrinsic apoptosis pathway.

Catecholamine induces endothelial dysfunction via Angiotensin II and intermediate conductance calcium activated potassium channel.

Endothelial dysfunction contributes to the pathogenesis of Takotsubo syndrome (TTS). However, the exact mechanism underlying endothelial dysfunction in the setting of TTS has not been completely clarified. This study aims to investigate the roles of angiotensin II (Ang II) and intermediate-conductance Ca2+-activated K+ (SK4) channels in catecholamine-induced endothelial dysfunction. Human cardiac microvascular endothelial cells (HCMECs) were exposed to 100 µM epinephrine (Epi), mimicking the setting of TTS. Epi treatment increased the ET-1 concentration and reduced NO levels in HCMECs. Importantly, the effects of Epi were found to be mitigated in the presence of Ang II receptor blockers. Furthermore, Ang II mimicked Epi effects on ET-1 and NO production. Additionally, Ang II inhibited tube formation and increased cell apoptosis. The effects of Ang II could be reversed by an SK4 activator NS309 and mimicked by an SK4 channel blocker TRAM-34. Ang II also inhibited the SK4 channel current (ISK4) without affecting its expression level. Ang II could depolarize the cell membrane potential. Ang II promoted ROS release and reduced protein kinase A (PKA) expression. A ROS blocker prevented Ang II effect on ISK4. The PKA activator Sp-8-Br-cAMPS increased SK4 channel currents. Epinephrine enhanced the activity of ACE by activating the α1 receptor/Gq/PKC signal pathway, thereby promoting the secretion of Ang II. The study suggested that high-level catecholamine can increase Ang II release from endothelial cells by α1 receptors/Gq/PKC signal pathway. Ang II can inhibit SK4 channel current by increasing ROS generation and reducing PKA expression, thereby contributing to endothelial dysfunction.

Tyrosinase deficiency impairs social novelty preference in mice.

OBJECTIVE: Tyrosinase is a rate-limiting enzyme for the biosynthesis of melanin pigment in peripheral tissues, such as skin and the retina. We recently reported the expression and enzymatic activity of tyrosinase as well as its protective effects against oxidative stress-induced protein damage in the mouse brain. The functional role of tyrosinase in the central nervous system, however, remains largely unknown. In the present study, we investigated the involvement of tyrosinase in social behavior in mice. METHODS: Pigmented C57BL/10JMsHir (B10) and tyrosinase-deficient albino B10.C- Tyr c /Hir (B10-c) mice were subjected to the three-chamber sociability test to assess sociability and social novelty preference. In addition, we measured the mRNA expression of genes involved in catecholamine metabolism in the hippocampus by real-time quantitative PCR analysis. RESULTS: The results obtained showed that tyrosinase deficiency impaired social novelty preference, but not sociability in mice. We also found that the hippocampal expression of genes involved in catecholamine metabolism, such as monoamine oxidase A and catechol-O-methyltransferase , were significantly decreased in tyrosinase-deficient B10-c mice. CONCLUSION: These results suggest that tyrosinase activity is functionally involved in the phenotypic expression of social behavior, particularly social novelty preference, in mice. The present study will advance our understanding of the functional role of tyrosinase in the central nervous system.

Automated online solid-phase extraction-tandem mass spectrometry detection for simultaneous analysis of acidic and alkaline catecholamines and their metabolites in human urine.

Metabolic dysregulation of catecholamines (CAs) is implicated in various human diseases. Simultaneously analyzing these acidic and alkaline CAs and their metabolites poses a significant challenge for clinical detection. This study introduces an efficient method employing automated online solid-phase extraction coupled with tandem mass spectrometry (aoSPE-MS/MS). The method employs weak cation exchange (WCX) and mixed-mode anion exchange (MAX) adsorbents to fabricate an on-line solid-phase extraction (SPE) column, along with an automated injection and multi-valve switching capabilities. The setup allows for automated extraction and analysis of urine samples in 15 minutes while retaining a wide range of acidic and basic CAs and their metabolites. The applicability of this method was demonstrated by optimising the adsorbent dosage volume, extraction solvent, and extraction rate. The limits of detection (LODs) and limits of quantitation (LOQs) for the 8 CAs and their metabolites were determined using the aoSPE-MS/MS approach, with ranges of 0.0625 ∼ 62.5 ng/mL and 0.125 ∼ 125 ng/mL, respectively. Additionally, assessments were made on the linearity, accuracy, and precision within and between batches, as well as matrix and ionic effects, and spiked recoveries. The study discovered that the aoSPE-MS/MS technique simplifies operation, increases efficiency, saves time, and has low detection and quantification limits when detecting a wide range of acid and alkaline CAs and their metabolites in urine. The study successfully demonstrated the high-throughput and automated detection of the 8 CAs and their metabolites with varying acidity and alkalinity in human urine samples. This method is expected to be a potential powerful tool for clinical detection.

Changes in blood catecholamines during induction of general anesthesia in patients with post-induction hypotension undergoing laparoscopic cholecystectomy: A single-center prospective cohort study.

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

Effect of age on amplitude of circulating catecholamine's change of healthy cyclic mares.

Catecholamines (CATs) are neurotransmitters and allostatic hormones whose plasma concentrations are physiologically modified in various species such as human, rats, mice and donkeys, with advancing age. However, currently these mechanisms are less well elucidated in horses and more specifically in mares. The hypothesis of this study was that, as in afore mentioned species, the CATs could experience physiological changes with advancing age. The objective of this study was to evaluate the concentrations of adrenaline (A), noradrenaline (NA), dopamine (DA), and serotonin (5-HT) in mares of different ages. Blood samples were drawn from 56 non-pregnant Spanish Purebred mares belonging to four different age groups: 6 to 9 years, 10 to 12 years, 13 to 16 years and > 16 years. The concentrations of A, NA, DA, and 5-HT were determined by competition EIA-Technical 3-CAt EIA, specifically validated for horses. Mares aged > 16 years showed lower A, DA, and 5-HT but higher NA concentrations than 6-9, 10-12, and 13-16 years (p < 0.05). Mares of 13-16 years showed lower A and higher NA than 6-9 and 10-12 years (p < 0.05). A and NA (r=-0.72; p < 0.05), and NA and 5-HT (r=-0.67; p < 0.05) were negatively correlated, and A and 5-HT (r = 0.74; p < 0.05) were positively correlated. Advanced age leads to a predominance of sympathetic nervous activity and lower serotonergic activity in non-pregnant mares.

Epithelium-derived 6-nitrodopamine modulates noradrenaline-induced contractions in human seminal vesicles.

AIMS: To evaluate the basal release of 6-nitrodopamine (6-ND) from human isolated seminal vesicles (HISV) and to characterize its action and origin. MAIN METHODS: Left HISV obtained from patients undergoing prostatectomy surgery was suspended in a 3-mL organ bath containing warmed (37 °C) and gassed (95%O2:5%CO2) Krebs-Henseleit's solution (KHS) with ascorbic acid. An aliquot of 2 mL of the supernatant was used to quantify catecholamines by LC-MS/MS. For functional studies, concentration-responses curves to catecholamines were obtained, and pEC50 and Emax values were calculated. Detection of tyrosine hydroxylase and S100 protein were also carried out by both immunohistochemistry and fluorescence in-situ hybridization assays (FISH). KEY FINDINGS: Basal release of 6-ND was higher than the other catecholamines (14.76 ± 14.54, 4.99 ± 6.92, 3.72 ± 4.35 and 5.13 ± 5.76 nM for 6-ND, noradrenaline, adrenaline, and dopamine, respectively). In contrast to the other catecholamines, the basal release of 6-ND was not affected by the sodium current (Nav) channel inhibitor tetrodotoxin (1 µM; 10.4 ± 8.9 and 10.4 ± 7.9 nM, before and after tetrodotoxin, respectively). All the catecholamines produced concentration-dependent HISV contractions (pEC50 4.1 ± 0.2, 4.9 ± 0.3, 5.0 ± 0.3, and 3.9 ± 0.8 for 6-ND, noradrenaline, adrenaline, and dopamine, respectively), but 6-ND was 10-times less potent than noradrenaline and adrenaline. However, preincubation with very low concentration of 6-ND (10-8 M, 30 min) produced significant leftward shifts of the concentration-response curves to noradrenaline. Immunohistochemical and FISH assays identified tyrosine hydroxylase in tissue epithelium of HISV strips. SIGNIFICANCE: Epithelium-derived 6-ND is the major catecholamine released from human isolated seminal vesicles and that modulates smooth muscle contractility by potentiating noradrenaline-induced contractions.