Adrenaline Research Articles

Laccase-Conjugated Nanostructured ZnFe2O4/rGO-Modified Electrode-Based Interfaces for Electrochemical Impedance Monitoring of Adrenaline: A Promising Biosensor for Management of Neurodegenerative Disorders.

A propitious biosensor for adrenaline (AD) detection in bovine serum albumin (BSA) real samples, which can be used for diagnosis and treatment of neurodegenerative disorders, is reported here. The biosensor consists of a La/ZF/rGO/ITO bioelectrode, which is fabricated by electrophoretic deposition of zinc ferrite/reduced graphene oxide (ZF/rGO) nanohybrid followed by drop casting of laccase (La) enzymes. The material characterization and electrochemical studies revealed that the ZF/rGO nanohybrid enhanced the electroactive surface and facilitated direct electron transfer between the electrode and electrolyte interface, resulting in enhanced electrocatalytic performance. The cyclic voltammetry and electrochemical impedance spectroscopy results asserted that the ZF/rGO nanohybrid decreased the charge-transfer resistance (Rct) and increased the surface adsorption, leading to a high diffusion coefficient (D) of 0.192 cm2/s. The biosensor exhibited a high sensitivity of 0.71 Ω/μM cm2, a good linear range (0.1 to 140 μM with R2 = 0.98), and a low limit of detection (LOD) is 12.5 μM, demonstrating the synergic effect of ZF and rGO in the La/ZF/rGO/ITO bioelectrode with AD. The biosensor also exhibited high selectivity and stability (55 days) in the presence of interfering substances and in BSA samples, with a recovery percentage close to 100 ± 5% RSD, indicating its potential biosensing applications for real-world applications in disease diagnostics, monitoring, and treatment.

Possible Regulation of P-Glycoprotein Function by Adrenergic Agonists II: Study with Isolated Rat Jejunal Sheets and Caco-2 Cell monolayers

To clarify the regulation of drug absorption by the enteric nervous system, we investigated how adrenergic agonists (adrenaline (ADR), clonidine (CLO), dobutamine (DOB)) and dibutyryl cAMP (DBcAMP) affected P-glycoprotein (P-gp) function by utilizing isolated rat jejunal sheets and Caco-2 cell monolayers. ADR and CLO significantly decreased the secretory transport (Papptotal) of rhodamine-123 and tended to decrease the transport via P-gp (PappP−gp) and passive transport (Papppassive). In contrast, DBcAMP significantly increased and DOB tended to increase Papptotal and both tended to increase PappP−gpand Papppassive. Changes in P-gp expression on brush border membrane by adrenergic agonists and DBcAMP were significantly correlated with PappP−gp, while P-gp expression was not changed in whole cell homogenates, suggesting that the trafficking of P-gp would be responsible for its functional changes. Papppassive was inversely correlated with transmucosal or transepithelial electrical resistance, indicating that adrenergic agonists affected the paracellular permeability. Adrenergic agonists also changed cAMP levels, which were significantly correlated with PappP−gp. Furthermore, protein kinase A (PKA) or PKC inhibitor significantly decreased PappP−gp in Caco-2 cell monolayers, suggesting that they would partly contribute to the changes in P-gp activity. In conclusion, adrenergic agonists regulated P-gp function and paracellular permeability, which would be caused via adrenoceptor stimulation.

Cortisol and epinephrine alter the adipose functions and the mobilization of PCBs in adipose tissue slices from elephant seal

Marine mammals are exposed to increasing intensities of anthropogenic stressors such as acoustic disturbance and contaminants. Correlative studies have suggested concerning shifts in behavioral and physiological status of stress-exposed individuals, which could alter the health and survival of marine mammal populations. However, functional studies of the effects of multiple stressors on marine mammals are lacking. To fill in this gap, we recently developed an ex vivo approach of precision-cut adipose tissue slices (PCATS) to study the impact of stressors on the function of an essential endocrine organ: the adipose tissue. In the present study, we investigated the impact of hormones associated with the stress response on adipose tissue from northern elephant seals (Mirounga angustirostris). Blubber biopsies were collected from 17 weaned northern elephant seal pups, separated into inner and outer layers, dissected into PCATS, and cultured for 48 hours. To mimic prolonged and short-term exposure to physiological stress, PCATS were treated with 2 µM cortisol (CORT) for the entire 48 hours or 100 nM epinephrine (EPI) for the last 12 hours of culture, respectively. Hormones were applied individually or in combination. CORT and EPI exhibited an interacting, blubber layer-dependent, effect on adipose tissue biology, as quantified by gene expression in PCATS, and release of glycerol, free fatty acids, leptin and polychlorinated biphenyls into culture media. EPI stimulated a higher rate of lipolysis than CORT in PCATS from both blubber layers. The combination of CORT and EPI upregulated the expression of adipose triglyceride lipase in inner blubber PCATS and downregulated hormone-sensitive lipase in outer blubber-derived PCATS. Expression of the leptin gene and secretion of the leptin adipokine were both decreased by EPI, while addition of CORT attenuated this effect in inner blubber PCATS only. CORT also increased the expression of the antioxidant enzyme glutathione peroxidase 3 in PCATS from both blubber layers. Polychlorinated biphenyls exhibited selective and limited mobilization from PCATS treated with stress hormones, highlighting the lipophilic properties of these toxic compounds. This study showed that physiological stress can impact several essential functions of marine mammal blubber, such as lipolysis and adipokine production.

Rapid electrochemical detection of epinephrine in human serum based on polydopamine-wrapped cerium oxide nanocomposite

Here, we report the development of a polydopamine (PDA) and CeO2 nanoparticle (NP) based electrochemical biosensor for the investigation of epinephrine (EP). PDA was decorated on CeO2 NPs through a simple mussel-inspired self-polymerization technique to produce a PDA@CeO2 nanocomposite, which is later dispersed on the surface of a working electrode. The optical, structural, morphological, and vibrational analysis of the nanocomposite is determined via UV–vis, XRD, SEM, and Raman techniques respectively. The electrocatalytic performance of PDA@CeO2/GCE was examined by using various electrochemical methods such as CV, DPV, and EIS. The fabricated PDA@CeO2-modified electrode shows good electrocatalytic activity to detect EP with high sensitivity and specificity. The electrochemical efficacy of PDA@CeO2/GCE is enhanced by its large specific surface area, high electrical conductivity, and enhanced active sites. Owing to excellent characteristics, the fabricated electrode has a lower detection limit of 8.37 μM in a wide linear range between 10 μM and 200 μM for EP detection. The PDA@CeO2/GCE performed exceptionally well in terms of selectivity, and repeatability. The analysis of EP in spiked human serum samples yielded consistent results with high sensitivity in a wide detection range between 20 μM and 100 μM with a detection limit of 14.79 μM. The recovery % of spiked serum samples fall between 97 and 105 % which indicates the practical utility of the proposed biosensor in real settings. Thus, the PDA@CeO2 nanocomposite is highly effective and has the potential to be utilized in a variety of applications due to its unique properties.

Bidirectional regulation effect of rhubarb as laxative and astringent by metabolomics studies

Ethnopharmacological relevanceRhubarb, a prominent traditional Chinese medicine, has been employed as a potent laxative for centuries and garnered particular popularity among the youth owing to its notable efficacy in weight management. Historical records indicated that rhubarb initially exhibited robust laxative properties, but extended and consistent usage may lead to an astringent response in the later stage of long-term use. In contrast, steamed pieces of rhubarb (SR), preparing through the process of steaming with wine, have demonstrated a gentle laxative effect with no reported adverse effects. Aim of the studyOur study was designed to explore the intricate mechanisms underlying laxative and astringent properties of rhubarb through metabolomics research. Materials and methodsIn this investigation, we employed a serum metabolomics approach utilizing the UPLC-Q-Extractive-Orbitrap-MS method to delve into the contrasting laxative and astringent effects of rhubarb, as well as to unravel the mechanisms of underpinning its bidirectional regulatory influence. To commence, we assessed alterations in Evacuation Index (EI) values, intestinal hormone levels, and colon histopathology in mice to gauge rhubarb's laxative and astringent effects. Subsequently, metabolomics methodology was employed for cluster analysis through Principal Component Analysis (PCA) and biomarker identification via Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA). Then, we delved into the distinctions in characteristic biomarkers, metabolic pathways, their association with pathological changes, and correlation heatmap for biomarkers between raw pieces of rhubarb (RR) and SR to gain insights into the potential mechanisms behind rhubarb's bidirectional regulatory effects. ResultsOur findings revealed that RR exhibited a laxative effect in the early stage and transitioned to an astringent effect in the later stage, as indicated by the EI values. In contrast, SR consistently demonstrated a mild laxative effect. Biochemical indexes and histopathological assessments unveiled that RR triggered its astringent effect by inhibiting secretion of motilin (MTL), promoting secretion of vasoactive intestinal peptide (VIP) and epinephrine (EPI), and inducing onset of inflammation. Furthermore, serum metabolomics analysis identified 59 discriminative biomarkers modulated by RR and SR. Through comprehensive analysis, we elucidated the in vivo transformation relationships among multiple endogenous metabolites. Notably, our results underscored the down-regulation of certain phosphatidylcholines (PCs), amino acids, acylcarnitines, and up-regulation of lysophosphatidylcholines (LysoPCs) played pivotal roles in the onset of gut dysfunction, intestinal inflammation, gut barrier damage, and gastrointestinal motility disorder upon prolonging RR administration, ultimately contributing to its astringent effect. Additionally, our correlation analysis elucidated that anthraquinones, stilbenes, and phenylbutanones were the pharmacodynamic material basis responsible for inducing the astringent effect of RR. ConclusionThis study provides valuable insights into the bidirectional regulatory effects of rhubarb and sheds light on its underlying mechanisms through a comprehensive metabolomics approach.

Ammodaucus leucotrichus Acts as an Antihypertensive and Vasorelaxant Agent Through sGC and Prostaglandin Synthesis Pathways.

Ammodaucus leucotrichus is a medicinal plant used in traditional medicine to treat various ailments, including hypertension. The study aimed to determine the antihypertensive activity of Ammodaucus leucotrichus. The study aimed to investigate the antihypertensive and vasorelaxant activities of the aqueous extract of Ammodaucus leucotrichus fruits (ALAE) in rats. ALAE was prepared to study its antihypertensive effect in L-NAME (Nω-L-arginine methyl ester)-induced hypertensive rats and its vasorelaxant activity in isolated thoracic aortas of rats. The acute and subchronic effects of ALAE on systolic, diastolic, mean arterial pressure, and heart rate (HR) were evaluated after oral administration of ALAE (60 and 100 mg/kg body weight) for 6 h for the acute experiment and over 7 days for the subchronic test. Isolated thoracic aortic rings were prepared to examine the vasorelaxant action of ALAE. Several common pharmacological agents were used to test potential pathways implicated in vasorelaxant action. The results showed that ALAE reduced blood pressure parameters (systolic, mean, and diastolic blood pressure) in L-NAME-induced hypertension rats after repeated oral treatment over seven days without affecting normotensive rats. Furthermore, in thoracic aortic rings pre-contracted with epinephrine (EP) (10 μM) or KCl (80 mM), ALAE (0.250-1.625 mg/ml) showed a vasorelaxant effect. In isolated rat thoracic aortas, blockage of soluble guanylyl cyslase with blue methylene (P < 0.01) partially decreased this vasorelaxant effect. In addition, blockage of the prostaglandin synthesis pathway with indomethacin (P<0.05) also reduced the vasorelaxant activity of ALAE. Pretreatment of aortic rings with glibenclamide, propanolol, L-NAME, MLN-4760, or nifedipine did not affect ALAE-induced vasorelaxation. Ammodaucus leucotrichus is a prescient medicinal plant, able to act as an antihypertensive agent. Moreover, the results suggest that the extract increased cGMP in NO-independent manner.

A graphitized carbon@boron carbide-mediated laccase-based amperometric biosensor for epinephrine detection

The development of novel electron transfer mediator is important for laccase-based electrochemical biosensors. Here, graphitized carbon coated boron carbide (GC@B4C) was first used as the mediator to transfer electrons from laccase (Lac) to nickel foam (NF) electrode. The GC shell of GC@B4C particles was characterized and confirmed by HRTEM, XRD and Raman spectroscopy. The fabricated Lac/GC@B4C/NF electrode was applied for amperometric detection of epinephrine (EP). Detection results indicated Lac/GC@B4C/NF electrode has wide linear range (0.1 µM-2.6 mM), low detection limit (40 nM), high sensitivity (76.05 µA mM−1), strong anti-interference ability and favorable stability for EP detection. This work opened up the use of nonmetallic carbide as the mediator for enzyme-based electrochemical biosensors.

Interference-free multimodal biosensing of adrenaline over other neurotransmitters: Role of 2-iminomethylenephenylboronic acid as the signal transduction unit of fluorescence and impedance

Aberrant levels of the neurotransmitters adrenaline (AD), noradrenaline (NA), and dopamine (DA) are linked to various diseases. Therefore, interference-free biosensing of neurotransmitters has become an important area of research. However, structural similarity (presence of diol/amine functionalities), small size, and neutral charge of the catecholamines add complexity to designing recognition systems and make the detection non-specific. Herein, we report a recognition unit 2-iminomethylenephenylboronic acid (2-IMPBA), which appears to be a remarkable transduction unit for the tailor-made development of biosensors for interference-free detection of the neurotransmitter AD via multiple techniques. Integrating a signaling unit 4-methylbenzothiazole-2-amine to 2- formylphenylboronic acid (2-FPBA), yielded a novel fluorosensor, which showed 38- fold fluorescence enhancement selectively with AD without any competition from other bioanalytes, including NA and DA. The attachment of 2-FPBA on the homemade plastic chip electrode surface afforded an impedimetric sensor that detects AD in the picomolar range without any challenge from its competitors. Both optical and electrochemical sensors have been tested for AD measurement in human plasma samples. We are not aware of any report describing the selective discrimination of AD from NA or other biomolecules commonly found in humanbiofluids.

Identification of Subjective Fatigue accompanied by Hypertension in Female Workers Making Tiles in Indonesia: A Cross-Sectional Survey

Introduction: The home industry has production process activities that are carried out manually. The release of the hormone adrenaline increases blood pressure through an increase in heart rate and arterial contractions, thereby accelerating the feeling of tiredness. As a result, female workers risk getting tired faster than men. Fatigue can lead to a decrease in productivity, poor quality of work, negatively affect the safety of workers, and increase the risk of work accidents. It aims to analyze the risk factors for subjective fatigue in female workers who have hypertension. Methods: This type of quantitative research with a cross-sectional design. Respondents were 278 female hypertension workers at the Karangasem Village Tile Making Home Industry Center, Wirosari District, Grobogan, Indonesia. Data analysis using Chi-square with the SPSS 21. Results: Of a total of 278 female workers, most were married (85.3%), did not smoke (98.9%), did not consume alcohol (96%), worked longer than 8 hours (93.5%), worked more than five years (80.9%), heavy workload (80.6%). Subjective fatigue factors related such as alcohol consumption habits (0.019), exercise habits (0.000), body mass index (0.000), working period (0.000), and workload (0.000). Meanwhile, other risk factors were not related, age (0.315), marital status (0.744), education level (0.811), smoking habits (0.236), disease history (0.762), length of work (0.530), type of work (0.393) and work stress (0.451). Conclusion: Risk factors that have a relationship with subjective fatigue are workload, BMI, alcohol consumption habits, exercise habits, and length of service

The Role of Adrenaline, Noradrenaline, and Cortisol in the Pathogenesis of the Analgesic Potency, Duration, and Neurotoxic Effect of Meperidine.

Background and Objectives: The purpose of the study was to investigate the role of adrenaline (ADR), noradrenaline (NDR), and cortisol in the pathogenesis of the analgesic potency, duration, and epilepsy-like toxic effect of meperidine. Materials and Methods: The experimental animals were separated into 11 groups of six rats. In the meperidine (MPD) and metyrosine + meperidine (MMPD) groups, paw pain thresholds were measured before and after the treatment between the first and sixth hours (one hour apart). In addition, ADR and NDR analyses were performed before and after the treatment, between the first and fourth hours (one hour apart). For the epilepsy experiment, caffeine, caffeine + meperidine, and caffeine + meperidine + metyrapone groups were created, and the treatment was applied for 1 day or 7 days. Groups were created in which caffeine was used at both 150 mg/kg and 300 mg/kg. Epileptic seizures were observed in epilepsy groups, latent periods were determined, and serum cortisol levels were measured. Results: In the MPD group, pain thresholds increased only at the first and second hours compared to pre-treatment, while ADR increased at the third hour, leading to a decrease in pain thresholds. In the MMPD group, the increase in paw pain thresholds at 1 and 6 h was accompanied by a decrease in ADR and NDR. In the caffeine (150 mg/kg) + meperidine group, 1-day treatment did not cause epileptic seizures, while seizures were observed and cortisol levels increased in the group in which treatment continued for 7 days. When cortisol levels were compared between the group in which caffeine (300 mg/kg) + meperidine + metyrapone was used for 7 days and the animals receiving caffeine (300 mg/kg) + metyrapone for 7 days, it was found that cortisol levels decreased and the latent period decreased. Conclusions: The current study showed that if serum ADR and cortisol levels are kept at normal levels, a longer-lasting and stronger analgesic effect can be achieved with meperidine, and epileptic seizures can be prevented.

Synthesis of 2D VO2 Nanosheets for the Dual Optical Sensor Method by Colorimetric and Fluorometric Sensing of Catecholamines.

For the first time, we report a dual optical sensor method (DOSM) using novel 2D VO2 nanosheets to act as fluorometric and colorimetric sensors to perform quantitative analysis of epinephrine (EP) and dopamine (DA). The wide color spectrum of the 2D vanadium oxidation series and specifically metastable blue 2D VO2 nanosheets were used to develop a DOSM biosensor. DA and EP are the major catecholamines in the human body that play vital roles as neurotransmitters and stress-responsive hormones of the endocrine system, respectively. Accurate and selective detection of these biomolecules can assist in the diagnosis of many neuroendocrine system-related diseases. The newly synthesized 2D VO2 nanosheet sensor showed bluish-green fluorescence as the first-ever fluorescence from 2D VO2 nanosheets. This sensor showed dual-function sensing toward EP by a dominant color change and fluorescence quenching. It is capable of individually detecting and quantifying both EP and DA with high selectivity and sensitivity by using both colorimetry and fluorometry simultaneously, with the detection limits of 1.07 and 5.54 μM for colorimetric analysis, respectively, and 48.07 and 3.98 μM for fluorescence analysis, respectively. The DOSM sensor was directly applied to real urine samples and gained satisfactory recovery above 90% by means of spiked concentrations. This study has opened a new platform using the DOSM and the vanadium oxidation spectrum in a much more effective way for biosensing. The fluorescence capabilities of this metal oxide can be further applied to many sensor applications based on both fluorescence and colorimetric detection.

SAT329 Case Series Of Patients With FGFR-1 Related Pheochromocytoma With A Focus On Biochemical And Imaging Signatures

Abstract Disclosure: S. Jhawar: None. J. Del Rivero: None. K. Pacak: None. Introduction: Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare neuroendocrine tumors arising from chromaffin cells of adrenal gland and neural crest, respectively. 40% of cases are associated with germline mutations and 30-40% somatic driver mutations. Here, we present two patients with PCC who were found to have somatic FGFR1 mutation. FGFR signaling is involved in regulation of tissue repair, angiogenesis, and inflammation. Patient 1: A 70-year-old female with a history of resistant hypertension, episodic palpitations and sweating presented with diffuse abdominal pain and chest tightness. She was noted to have a blood pressure of 220/160 mm Hg. CT scan showed a 4.2 x 3.9 cm left adrenal mass, suspicious for malignancy and a &amp;lt;1 cm retroperitoneal mass. Blood work revealed elevated plasma normetanephrine (NM) 3543 pg/mL (normal 0- 145) and metanephrine (MN) 871 pg/mL (normal 0-62). 18F-FDG PET/CT showed a left adrenal mass without abnormal FDG activity. 68Ga-DOTATATE PET/CT was compatible with left PCC (SUVmax 28). 18F-DOPA PET/CT showed left PCC and a small retroperitoneal PGL. Two weeks after initiating phenoxybenzamine, she underwent total left adrenalectomy. Pathology was consistent with PCC. Molecular testing revealed FGFR1 pathogenic somatic mutation (c.1638C&amp;gt;G p.Asn546Lys). Patient 2: A 73-year-old male with known left renal cell carcinoma presented to our institution for management of recurrent right PCC. He was found to have a 3.8 cm right adrenal incidentaloma eight years ago and elevated plasma NM 6.3 nmol/L (normal &amp;lt;0.9), MN 1.5 nmol/L (normal &amp;lt;0.5). He underwent total right adrenalectomy, and the diagnosis of PCC was confirmed on histopathology. Two years later, he developed a 5.1 x 4.7 cm nodular mass in the right adrenal fossa and a &amp;lt;1 cm liver lesion on CT scan. The adrenal lesion showed intense avidity on 68Ga-DOTATATE PET/CT and 18F-DOPA PET/CT and mild avidity on 18FDG-PET/CT. 18F-DOPA PET/CT also showed avidity towards the liver lesion. He was started on doxazosin and underwent laparoscopic right adrenalectomy. Pathology demonstrated PCC. Whole exome sequencing of the tumor showed pathogenic FGFR1 mutation (c.1638C&amp;gt;G, p.Asn546Lys). Discussion: Activating FGFR1 mutations are associated with sporadic PCC. The biochemical phenotype of our patients showed higher levels of NM than MN. The imaging profile revealed that 18F-DOPA PET/CT was more sensitive than 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT as it showed avidity towards other extra-adrenal lesions. Further studies in larger cohorts are needed to enhance understanding of pathogenesis, biochemical and imaging phenotype, which will help tailor the treatment and potential development of novel targeted therapies. Presentation: Saturday, June 17, 2023

FRI204 A Rare Case Of Cushing Syndrome In Pregnancy: Diagnosis And Therapeutic Challenges

Abstract Disclosure: Z. Cardona: None. E.D. Szmuilowicz: None. Introduction: Cushing’s syndrome (CS) rarely occurs during pregnancy, and diagnosis of Cushing’s syndrome in pregnancy is challenging due to physiologic changes during gestation. CS is associated with severe maternal and fetal complications. Clinical Case: A 36-year-old woman presented at 21 weeks gestational age with a known adrenal nodule admitted for evaluation of HTN, bilateral lower extremity edema, transaminitis, hyperglycemia, and acute hypoxemic respiratory failure. Reported proximal muscle weakness, facial swelling, anxiety, depression, perspiration, and headaches associated with HTN. Physical exam notable for mild supraclavicular fat deposition, chest and neck plethora, hypertrichosis, and bruising. CT abdomen pelvis revealed a 2.3-cm left adrenal nodule measuring 30 Hounsfield units. Biochemical evaluation included a plasma renin activity of 0.719 ng/mL/h [ref range: 0.167-5.380 ng/mL/h], aldosterone &amp;lt;1.0 ng/dL [ref range: 0.167-5.380 ng/dL], potassium 2.6 mEq/dL, free plasma metanephrines (MN) &amp;lt; 25 pg/mL [ref range: &amp;lt; or = 57 pg/mL], free normetanephrines (NMN) &amp;lt; 25 pg/mL [ref range: &amp;lt; or = 148 pg/mL, total free MN and NMN &amp;lt; 25 [ref range: &amp;lt; or = 205 pg/mL]. 24-hour urine free cortisol (UFC) was markedly elevated at 1854.1 mcg/24h [ref range: 3.1-50.0 mcg/24h], repeat 2186.2 mcg/24h, ACTH: 1.5 pg/mL [ref range: 7.2-63.6 pg/mL], confirming a diagnosis of ACTH-independent CS. Her case was complicated due to the adrenal nodule location. Patients with left adrenal nodules are at risk of developing inferior vena cava (IVC) syndrome during left adrenalectomies, especially in the third trimester, due to compression exerted by the uterus while lying on the right side during the procedure. She underwent an uncomplicated laparoscopic left adrenalectomy. Was started on hydrocortisone (HC) following surgery. There was concern for transient neonatal adrenal insufficiency at delivery. Measuring adrenal insufficiency in utero is challenging; however, estriol could serve as a surrogate marker of fetal adrenal function. Her estriol was normal, possibly indicating intact fetal adrenal activity. She had an uncomplicated vaginal delivery with no signs of adrenal insufficiency in her baby. Interestingly, she had a severely low alkaline phosphatase (ALP) which completely normalized soon after adrenalectomy. Clinical Lesson: This case depicts the challenges in managing CS in pregnancy and its repercussions regarding maternal, fetal, and delivery outcomes. Additionally, it highlights the importance of implementing a multidisciplinary approach, including obstetricians, endocrinologists, endocrine surgeons, and pediatricians, to ensure the optimization of therapeutic strategies. Presentation: Friday, June 16, 2023

Neurotransmitter Assay for In Vivo Nerve Signal Detection Using Bismuth Immobilized on a Carbon Nanotube Paste Electrode.

Voltammetric analysis of the neurotransmitter epinephrine (EP) was performed using bismuth immobilized on a carbon nanotube paste electrode (BCE), whose properties were compared with those of a carbon nanotube paste electrode (CE). BCE was found to be more efficient in detecting EP. The analytical parameters used were 0.3 V square-wave (SW) stripping voltammetric amplitude, 400 Hz frequency, -0.8 V initial potential, and 0.015 V increment potential. The optimized conditions were applied to an assay of a carp's front fin. A BCE was inserted into a carp's front fin muscle, and a stimulus was given every 50 s. This circuit is easy to use and does not require much analytical preparation time. The working electrode is miniscule, and its detection limit is very low. The in vivo muscle's chronoamperometric nerve currents were analyzed. These results have potential for applications in medical diagnostics, pharmaceuticals, interface controllers, and other fields.

Efficacy of Flavonoid Apigenin on Hemodynamic indices, Baroreflex Function, Cardiac and Kidney Remodeling and Vasoactive-Inflammatory Biomarkers in Experimental Renal Hypertension

The hypothesis stated here that, the long-term prevention by natural flavonoid phenolic compound, for example apigenin (Apg), improves baroreflex sensitivity and vascular resistance and occurs beneficial action for attenuation the renal hypertension (RH). One-kidney, 1-clip rats (1K1C) were treated with Apg for 2 weeks after 1 week of surgical intervention. At the end of the study in the control RH group the blood pressure (BP) increased on average by 43.5%, decreased in heart period (HP) by 9.8%, cardiochronotropic (vagal) component of baroreflex sensitivity (BRS) by 50%, and adrenergic component by 34%. Thus, in 1K1C experimental model of hypertension, provides switching to parasympathetic component and accompanied with proportionally nearly two-fold increase in epinephrine (EPN) and norepinephrine (NE) without changes in EPN/NE ratio. Morphometric changes in the kidney and heart confirmed the development of kidney and cardiac hypertrophy and renal functioning disturbances (blood urea nitrogen (BUN) increased in more than two-fold) and markers of sodium reabsorption in proximal tubule, total trans-EETs, decreased in 1.6-fold. The pronounced increased proinflammatory cytokines, interleukin 1b (IL1 b), endothelin -1 (ET-1) and tumor necrosis factor (TNF)-a confirmed the formation of “sterile inflammation” which strengthening by the nearly two-fold decreasing in the level of anti-inflammatory (vasodilatory) mediators, prostaglandin E2 (PGE2). Preventive long-term regime treatment with Apg (5mg/kg i.p./daily) in RH rats significantly decreased BP by 18.6%, increased parasympathetic component of BRS by 38.5% without marked altered its sympathetic component. Such deremodeling in BRS sensitivity associated with significant decreased in heart and kidney hypertrophy and functional activity of kidney, normalization of BUN and total EETs, reducing in circulating plasma level of catecholamines, and markedly attenuated progression of inflammation, decreased of proinflammatory levels of cytokines. Thus, Apg provides preventive beneficial pluripotent action in RH rats by exerting antihypertensive, cardio- and renoprotective effects and attenuation of “sterile inflammation”.

Effects of dietary tryptophan supplementation on rectal temperature, humoral immunity, and cecal microflora composition of heat-stressed broilers.

This trial aimed to determine the effects of tryptophan (Trp) on the rectal temperature, hormone, humoral immunity, and cecal microflora composition in broiler chickens under heat stress (HS). One hundred and eighty 18 days-old female Arbor Acres broilers were randomly divided into three treatment groups, with six replicates of ten birds in each replicate. The broilers were either raised under thermoneutral conditions (TN, 23 ± 1°C) or subjected to heat stress (34 ± 1°C for 8 h daily). The TN group received a basal diet, and another two heat-stressed groups were fed the basal diet (HS) or the basal diet supplemented with 0.18% Trp (HS + 0.18% Trp) for 21 consecutive days. The basal diet contained 0.18% Trp. Results revealed that HS increased the rectal temperature, serum epinephrine (EPI), and corticotropin-releasing hormone (CRH) concentrations (p < 0.05), reduced the bursal index, the levels of serum immunoglobulin A (IgA), IgG, IgM, and serotonin (5-HT) as well as the relative abundance of Actinobacteria in cecum (p < 0.05) compared with the TN group. Dietary supplementation of Trp decreased the rectal temperature, serum dopamine (DA), EPI, and the levels of CRH and L-kynurenine (p < 0.05), increased the bursal index, the levels of serum IgA, IgM, and 5-HT as well as the relative abundance of Ruminococcus torques group in cecum of heat-stressed broilers (p < 0.05) compared to HS group. In conclusion, dietary Trp supplementation decreased rectal temperature, improved cecal microbiota community and Trp metabolism, and enhanced humoral immunity of heat-stressed broilers.

Electro-sensitive detection of adrenaline and paracetamol at SrF/MWCNT modified carbon paste electrode

Strontium ferrate nanoparticles (SrF/NPs) were synthesised using the co-precipitation method in this study, and the process was examined using spectroscopic techniques from the scanning electron microscope (SEM), energy dispersive spectroscopy (EDS), and X-ray diffraction (XRD). Multi-walled carbon nanotube (MWCNT) and strontium ferrite nanoparticle (SrF/NP) were combined with carbon paste to modify the carbon paste electrode (CPE). The SrF/MWCNT/MCPE has greater electrocatalytic activity and sensitivity towards the detection of paracetamol (PA) in the presence of adrenaline (AD), as shown by electrochemical characterization utilising cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The limits of detection for PA and AD were determined to be 6.4 µM and 5.8 µM, respectively, while the limits of quantification were found to be 20 µM for PA and 18.1 µM for AD using CV methods. The development of a selective simultaneous study for PA, AD, and FA (folic acid) was made possible by effective separation at BCPE and MCPE, DPV techniques confirmed that there is no interference between binary analytes, and the proposed MCPE identifies the PA tablet sample with successful recovery.

Bioinspired CuZn-N/C Single-Atom Nanozyme with High Substrate Specificity for Selective Online Monitoring of Epinephrine in Living Brain.

Though many elegant laccase mimics have emerged, these mimics generally have no substrate selectivity as well as low activity, making it difficult to fulfill the demand for monitoring in physiological conditions. Herein, inspired by the Cu-N ligand structure in the active site of natural laccase, we revealed that a carbon nanomaterial with atomically dispersed Cu and Zn atoms (CuZn-N/C) and a well-defined ligand structure could function as an effective laccase mimic for selectively catalyzing epinephrine (EP) oxidation. Catalytic activity of the CuZn-N/C nanozyme was superior to those of Cu-N/C and Zn-N/C and featured a Km value nearly 3-fold lower than that of natural laccase, which indicated that CuZn-N/C has a better affinity for EP. Density functional theory (DFT) revealed the mechanism of the superior catalytic ability of dual-metal CuZn-N/C as follows: (1) the exact distance of the two metal atoms in the CuZn-N/C catalyst makes it suitable for adsorption of the EP molecule, and the CuZn-N/C catalyst can offer the second hydrogen bond that stabilizes the adsorption; (2) molecular orbitals and density of states indicate that the strong interaction between the EP molecule and CuZn-N/C is important for EP catalytic oxidization. Furthermore, a sensitive and selective online optical detection platform (OODP) is constructed for determining EP with a low limit of detection (LOD) of 0.235 μM and a linear range of 0.2-20 μM. The system allows real-time measurement of EP release in the rat brain in vivo following ischemia with dexmedetomidine administration. This work not only provides an idea of designing efficient laccase mimics but also builds a promising chemical platform for better understanding EP-related drug action for ischemic cerebrovascular illnesses and opens up possibilities to explore brain function.

Sympathetic nervous system responses to acute psychosocial stress in male physicians with clinical burnout

BackgroundOccupational burnout has been associated with an increased risk of cardiovascular disease, with sympathetic nervous system (SNS) dysfunction as one explanation. This study examined the effects of burnout on responses of SNS activity measures to acute psychosocial stress in male physicians, a population at risk for burnout. MethodsStudy participants were 60 male physicians, 30 with clinical burnout, assessed with the Maslach Burnout Inventory, and 30 without burnout (controls). All participants underwent the 15-min Trier Social Stress Test. Heart rate, blood pressure, salivary alpha-amylase, and plasma levels of epinephrine (EPI) and norepinephrine were assessed pre-stress, immediately post-stress, and 15 min and 45 min post-stress. ResultsPhysicians with burnout and controls differed in EPI changes over time, controlling for age, job stress and anxiety symptoms (F (3,147) = 5.18, p = .002 for 'Time by Group' interaction; η2p = .096). Burnout was associated with a smaller increase in EPI from pre-stress to immediately post-stress (r(54) = −.40, p = .004). The emotional exhaustion dimension of burnout was a significant driver of this effect. The area under the curve with respect to increase in EPI was also smaller in the burnout group (F (1,49) = 6.06, p = .017, η2p = .110). Group differences were not significant for the other SNS activity measures. ConclusionsBurnout may be linked to dysfunction of the sympathoadrenal medullary (SAM) system, when exposed to acute psychosocial stress. In keeping with the allostatic load concept, an insufficient SAM stress response in burnout could potentially contribute to cardiovascular disease.

Catechol oxidase nanozyme based colorimetric sensors array for highly selective distinction among multiple catecholamines

In order to effectively monitor multiple catecholamine (CA) neurotransmitters with extreme similar structures, a rapid, sensitive and selective detection strategy has become an urgent problem to be solved. In this paper, a novel colorimetric sensors array based on CuNCs protected by various ligands such as tannic acid, ascorbic acid and polymethylacrylic acid (CuNCs@TA, CuNCs@AA and CuNCs@PMAA) was constructed. All of these CuNCs could mimic catechol oxidase to selective catalyze catechol-type analogues (such as CAs) to corresponding quinones along with color changes. Furthermore, experiments and theory calculations demonstrated that Cr6+-modification on the surface of CuNCs facilitated the steady-state kinetics of enzymatic activity. Based on these CuNCs as sensing probes, this sensors array can quickly detect different CAs (such as epinephrine (EP), including dopamine (DA), norepinephrine (NE) and l-dopa) with similar structures. When those analogues were added to the CuNC-based colorimetric array sensors, different absorbance changes were produced at 485 nm. Linear discriminant analysis (LDA) showed that the tri-probe colorimetric array sensors could recognize and distinguish these analogues, and corresponding binary and ternary mixtures could be well categorized. The value of Factor 1 of an array with varied CA concentrations had a good linear correlation, and the detection limit (LOD) was as low as 10−8∼10−9 mol/L. Four CA analogues in real samples were identified by CuNCs-based colorimetric array sensors. This work provides a fast and convenient experimental basis for monitoring the complex structure CAs neurotransmitters.