Epinephrine Concentrations Research Articles

Activatable NIR Fluorescence Probe for Epinephrine Detection and Bioimaging Based on Anionic Heptamethine Cyanine.

Epinephrine (EP) is an essential catecholamine in the human body. Currently, most EP detection methods are not suitable for in vivo detection due to material limitations. An organic small molecule fluorescent probe based on a chemical cascade reaction for the detection of EP was designed. Anionic heptamethine cyanine dye was selected as a fluorescent dye because of its NIR fluorescence emission with excellent biocompatibility. The secondary amine of EP nucleophilically attacks the carbonate of the probe with its stronger nucleophilicity and further undergoes intramolecular nucleophilic cyclization to release the fluorophore. Other substances containing only primary amines or no β-OH lack reaction competitiveness due to their weaker nucleophilicity or inability to undergo further cyclization. The fluorescence recovery of the probe was linearly related to the EP concentration of 2-75 μmol/L. The detection limit was 0.4 μmol/L. The recovery rate was 94.78-111.32%. Finally, we successfully achieved bioimaging of EP in living cells and EP analogue in nematodes.

Effects of Transportation on Blood Indices, Oxidative Stress, Rumen Fermentation Parameters and Rumen Microbiota in Goats.

The objective of this experiment was to delve into the impacts of transportation on goats. Sixteen healthy goats were selected as experimental animals; these goats were transported at a speed ranging from 35 to 45 km/h for 20 h. The changes in the physiological indexes, blood physiological indexes, biochemical indexes, rumen fermentation indexes, and rumen microbial structure composition of goats before and after transportation were measured. The results showed that after transportation, the contents of IgM, IgA, IgG, and Thyroxine decreased very significantly, while the contents of propionic acid, Hemoglobin and Epinephrine significantly increased, and the contents of VFA, acetic acid, butyric acid, isobutyric acid, isovaleric acid, LPS, IL-1β, IL-6, TNF-α, Major Acute Phase Protein, protein carbonyl, and cortisol increased very significantly. There was no significant difference in α-diversity and β-diversity, and the relative abundance of rumen microorganisms was not significantly different at either phylum or genus levels. The experimental findings revealed that continuous transportation for a duration of 20 h can induce a severe stress response in goats, leading to compromised immune function, diminished antioxidant capacity, escalated inflammatory response, and altered rumen fermentation indices. However, the experiment did not reveal any significant impact on the structure and composition of the rumen microbiota.

Influence of epinephrine reactivity to stress on meat quality in goats.

The magnitude of physiological responses to a stressor can vary among individual goats within a herd; however, whether these differences can differentially affect meat quality is not known. This study was conducted to determine the influence of the magnitude of epinephrine response (ER) to acute stress on muscle metabolome and meat quality in goats. Male Spanish goats (6 mo old) were transported for 180min. (N = 75 goats; 25 goats/d) to impose stress. Blood samples were obtained after transport for analysis of physiological responses. Goats were slaughtered using humane procedures and samples were collected for muscle metabolomics and meat quality analyses. The data obtained from blood and muscle/meat analysis were then categorized based on epinephrine concentrations into low (LE), medium (ME), and high (HE) ER groups (n = 12/ER group). The physiological and meat quality variables were analyzed as a Completely Randomized Design in SAS, and metabolomics data were analyzed using R software. Plasma glucose concentrations were significantly high in the HE group, low in the LE group, and intermediate in the ME group (P < 0.05). However, leukocyte counts and cortisol, norepinephrine, blood urea nitrogen, and creatine concentrations were not different among the ER groups. Muscle (Longissimus dorsi) glycogen concentrations (15min postmortem) were significantly higher (P < 0.05) in the ME and LE groups than in the HE group. However, postmortem Longissimus muscle pH and temperature (15min and 24h), 24h calpastatin and desmin levels, and rib chop color (L*, a*, and b*), cooking loss, and Warner-Bratzler shear force values were unaffected by ER. Targeted metabolomics analysis of Longissimus muscle (15min) revealed that diacyl phosphatidylcholines (C38:0; 40:6) and sphingomyelin (C20:2) were significantly different (P < 0.05) among the ER groups, with the concentrations of these metabolites being consistently high in the LE group. These differential muscle metabolite concentrations suggest that ER can influence biochemical pathways associated with cell membrane integrity and signaling. ER had a significant effect on dopamine concentrations, with the levels increasing with increasing levels of ER. The results indicate that differences in epinephrine reactivity can influence selected physiological responses and muscle metabolites; however, it does not significantly influence meat quality attributes.

Ground-based adaptive horsemanship lessons for veterans with post-traumatic stress disorder: a randomized controlled pilot study.

Equine-assisted services (EAS) has received attention as a potential treatment strategy for post-traumatic stress disorder (PTSD), as existing literature indicates that symptoms may decrease following EAS. Relatively little is known about the mechanisms at play during lessons and if physiological measures are impacted. The objectives of this pilot study were to 1) explore the effects of adaptive horsemanship (AH) lessons on symptoms of PTSD, hormone concentrations, and social motor synchrony; 2) determine if physiological changes occur as veterans interact with horses; and 3) explore if the interaction between veteran and horse changes over the 8-week session. Veterans with PTSD were randomly assigned to control (CON, n = 3) or AH (n = 6) groups for an 8-week period (clinical trial; NCT04850573; clinicaltrials.gov). Veterans completed the PTSD Checklist (PCL-5) and Brief Symptom Inventory (BSI) at pre-, post-, and 2- and 6-month follow-up time points. They also completed a social motor synchrony test (pendulum swinging) and blood draw at pre- and post-time points. In weeks 1, 4, and 8, blood samples were drawn at 0 min, 3 min, 5 min, 25 min, and 30 min during the 30-min AH lessons. Veterans completed the Human-Animal Interaction Scale (HAIS) after each lesson. Blood samples were assayed for plasma cortisol, epinephrine, norepinephrine, and oxytocin. Data were analyzed with repeated measure ANOVAs. Changes in PTSD symptoms from pre- to post-time point were analyzed with paired t-tests. Changes in PCL-5 scores tended to differ (p = 0.0989), and global BSI scores differed (p = 0.0266) between AH (-11.5 ± 5.5, mean ± SE; -0.5 ± 0.2) and CON (5.3 ± 5.4; 0.4 ± 0.2) groups. Social motor synchrony and hormone concentrations did not differ between groups or time points (p > 0.05). Cortisol, norepinephrine, and oxytocin concentrations did not differ across sessions (p > 0.05). Epinephrine concentrations tended (p = 0.0744) to decrease from week 1 to 4 of sessions. HAIS scores increased (p ≥ 0.0437) in week 3 and remained elevated as compared to week 1. Participant recruitment was the greatest challenge. These preliminary results agree with the literature suggesting that EAS can reduce symptoms of PTSD.

A novel copper ion enhanced electrochemical DNA biosensor for the determination of epinephrine

A novel electrochemical biosensor was developed for the detection of epinephrine (EP) by immobilizing double-strand DNA (dsDNA) bound with copper ions on a gold electrode (Cu2+/dsDNA/MCH/AuE). The electrochemical behavior of EP at Cu2+/dsDNA/MCH/AuE was examined, and the results demonstrated a significant enhancement in the electrocatalytic oxidation peak current of EP due to the formation of a stable G-Cu(II)-G sandwich structure between Cu2+ and guanine at the modified electrode. The modification process of the electrode was characterized by scanning electron microscopy, infrared spectroscopy, electrochemical impedance spectroscopy, and differential pulse voltammetry. A study on the effect of pH in phosphate buffer solution on the electrochemical oxidation of EP indicated that the catalytic oxidation process was pH-dependent. A plot of catalytic current versus EP concentration exhibited a dual-linear relationship within two ranges: 1.0–12.5 μM and 12.5–1000.0 μM, with correlation coefficients of 0.995 and 0.997, respectively. The limit of detection was determined to be 47 nM (S/N = 3). According to the calculated Hill coefficient (0.99), it can be concluded that the electrocatalytic process followed the Michaelis-Menten kinetic mechanism. The maximum catalytic current Im was 25 μA, while the apparent Michaelis-Menten constant Km was 1.425 mM. These findings indicated excellent electrocatalytic activity of the modified electrode towards oxidation of EP. The developed biosensor successfully detected EP in spiked mouse serum as well as epinephrine hydrochloride injection with high selectivity, sensitivity, stability, and accuracy.

The Effect of Coffee Consumption on the Level of Adrenalin Blood Serum in the Periodontitis Model: An In Vivo Study

Background: Adrenalin was supposed to have an anti-inflammatory effect; hence adrenalin concentration in blood serum might be lower in inflammatory diseases. Coffee contains caffeine that is thought to have the potency to increase adrenalin secretion in inflammatory diseases. This study aimed to analyze the effect of coffee consumption on adrenalin blood levels in periodontitis rat model. Methods: This in vivo experimental study used the post-test-only control group design. Wistar male rats (Rattus novergicus) were divided into four groups (four rats/group) i.e. 1) Periodontitis (no coffee), 2) periodontitis + coffee, 3) Coffee (no periodontitis), 4) Control (no coffee, no periodontitis). The periodontitis rat model was made by injecting periodontitis bacteria Phorpyromonas gingivalis in the buccal mucosa of the lower molar tooth three times a week for 4 weeks. A single dose (0.6 mL d–1) of ground coffee infusion (equal to one cup per day for humans) was given to each rat in the coffee group, for 28 d. At the end of the study, all of the rats were sacrificed and blood was drawn intra-cardially. Blood serum adrenalin concentration was analyzed using Enzyme-linked immunosorbent assay (Elisa). Results: The Periodontitis group showed significantly lower serum adrenalin (p&lt; 0.05) than others. Coffee consumption in periodontitis rats affected a significantly higher adrenalin blood serum level (p &lt; 0.05). Conclusion: Coffee consumption could replenish the level of blood serum adrenalin which decreases in periodontitis. Further studies are needed to elucidate the modulation mechanism of coffee-adrenalin-inflammation.

Sublingual sufentanil does not decrease tolerance to progressive central hypovolemia

Hemorrhage is a leading cause of death in both civilian and battlefield settings. Since pain often accompanies a hemorrhagic insult, the administered pain medication must not interfere with critical autonomic responses beneficial to maintaining arterial blood pressure and thus organ perfusion. Sublingual sufentanil is currently available for administration on the battlefield, but its effect on hemorrhage tolerance is unknown. This study tested the hypothesis that sufentanil impairs tolerance to progressive central hypovolemia in awake humans. METHODS: 29 participants, 15 males and 14 females (aged: 29 ± 5, weight: 74 ± 8 kg, BMI: 25 ± 2 kg/m2) participated in this double-blinded, randomized, placebo-controlled trial. Following sublingual administration of sufentanil (30 μg) or placebo, participants completed a progressive lower-body negative pressure (LBNP) protocol starting at 40 mmHg that was further reduced by 10 mmHg every three minutes until presyncope. Presyncope was defined as: continued reports of feeling faint and/or nauseous, a rapid decline in blood pressure resulting in systolic blood pressure &lt;80 mmHg, and/or relative bradycardia accompanied by a narrowing of pulse pressure. Tolerance to LBNP, quantified as cumulative stress index (mmHg*min), was compared between sufentanil and placebo trials using a Wilcoxon Signed rank test. Arterial blood pressure, heart rate, and plasma catecholamine concentrations were compared using mixed effects models (LBNP stage x Drug). RESULTS: Tolerance to LBNP was not different between trials (sufentanil: 518 ± 203 vs. placebo: 594 ± 267, p = 0.495). Mean blood pressure decreased similarly between the two trials during LBNP (sufentanil: -23 ± 9 mmHg vs. placebo: -22 ± 10 mmHg, p&lt; 0.001), with no main effect of drug (p = 0.498) or interaction (p = 0.935). Increases in heart rate with LBNP were similar between the two trials (sufentanil: 44 ± 25 bpm vs. placebo: 52 ± 23 bpm, time: p &lt; 0.001) with no main effect of drug (p=0.626) or interaction (p = 0.424). Epinephrine (drug: p = 0.004, time: p &lt; 0.001, interaction: p = 0.031) and norepinephrine (drug: p = 0.017, time: p &lt; 0.001, interaction: p = 0.161), concentrations increased to LBNP, with post hoc analysis revealing that epinephrine concentrations were higher at LBNP 50 and presyncope (p ≤ 0.05) with sufentanil. CONCLUSION: These data demonstrate that sublingual sufentanil does not impair tolerance to simulated hemorrhage or alter the assessed mechanisms responsible for maintaining arterial blood pressure. W81XWH-22-C-0004. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

DOPAMINE-DEPENDENT FORM OF ARTERIAL HYPERTENSION IN PATIENTS WITH A HIGH DEGREE OF NUTRITIONAL-CONSTITUTIONAL OBESITY

Objective: Despite significant advances in the study of the pathogenesis, clinical picture and treatment of arterial hypertension (AH), the role of the dopaminergic system in obese patients remains insufficiently studied. Aim: To evaluate the effectiveness of the use of D2 receptor agonists in patients with arterial hypertension (AH) and nutritional-constitutional obesity (NCO) of the 3rd degree. Design and method: We examined 151 patients aged 30-60 years (65 men, 86 women) with AH and NCO. The control group (CG) consisted of 78 hypertensive patients. Daily monitoring of blood pressure (BP), body mass index (BMI), daily excretion of dopamine, plasma levels of aldosterone, prolactin, leptin, adrenaline, creatinine, lipid spectrum - obese patients were divided into two groups. In addition to basic antihypertensive therapy, patients 1 group (n=74) were prescribed bromocriptine (0.08 mg/kg in three doses), patients 2 group (n=71) – pramipexole (0.125 mg 3 times/day). Results: During the baseline examination, daily dopamine excretion in obese patients was 1.6 times lower (p&lt;0.001) than in control group patients. A negative correlation was found between dopamine excretion and BMI (r=-0.6; p&lt;0.001). In patients with hypertension and NCO, a basic examination revealed a significant (p&lt;0.001) increase in the plasma concentrations of prolactin (2.5 times), aldosterone (1.5 times), leptin (3.4 times) and adrenaline (by 1.3 times) compared to CG. Taking bromocriptine for 8 weeks in patients 1 group led to a decrease in blood pressure, BMI and plasma levels of prolactin and aldosterone. In 41.9% of patients 1 group with dopamine excretion levels less than 300 nmol/day, normalization of blood pressure was observed. In patients 2 group pramipexole was discontinued due to side effects. Conclusions: In the majority of patients with hypertension and NCO (58.1%), the main pathogenetic factor in increasing blood pressure is a low level of dopamine and a compensatory increase in prolactin, aldosterone, and adrenaline in plasma. The use of the D2-dopamine receptor agonist bromocriptine helps to normalize the daily excretion of dopamine, reduce the levels of prolactin, aldosterone and adrenaline, blood pressure and BMI. The use of pramipexole in patients with hypertension and NCO seems inappropriate

АНАЛИЗ АГРЕГАЦИИ ТРОМБОЦИТОВ У ПАЦИЕНТОВ С СИНДРОМОМ ДИАБЕТИЧЕСКОЙ СТОПЫ

Purpose. To analyze the aggregation function of platelets in patients with diabetic foot syndrome (DFS). Material and methods. Prospective clinical trial in which 31 patients participated have been conducted by us. To achieve this purpose, 2 groups have been formed: group 1 – patients with no history of diabetes (n=17); group 2 – patients with diabetes mellitus type 2 complicated by DFS (n=14). The studying of platelet aggregation was carried out once for first days after the admission of patients to the general somatic health care units, turbidimetric count method with an inductor: adenosine diphosphate (ADP) (concentrations of 0.3 mcg/ml, 0.6 mcg/ml, 1.25 mcg/ml and 2.5 mcg/ml were used), adrenaline (concentrations of 2.5 microns and 5.0 microns were used), collagen – 2 mg/ml. Results. In group 2 patients, the average platelet aggregation time, as well as in group 1, was lower than the reference values with an ADP inducer at a dose of 0.6 mcg/ml, 1.25 and 2.5 mcg/ml, and higher with adrenaline at a dose of 2.5 microns and with adrenaline at a dose of 5.0 microns. The degree of aggregation was lower than normal when used with all inducers except ADP 0.3 mcg/ml (normal), and the average platelet aggregation rate was lower with adrenaline. With the other inducers, platelet aggregation parameters were within the reference values. When adding inducers with all platelet aggregation parameters, significant differences were obtained between the two groups (p&lt;0.05), and only when using ADP at doses of 0.6 mcg/ml, 1.25 mcg/ml and 2.5 mcg/ml, no significant differences were obtained for the aggregation rate parameter (p&gt;0.05). Conclusion. In patients with DFS, compared with the people without diabetes mellitus type 2, the lowest degree of aggregation is noted with the use of ADP and adrenaline, the aggregation time is less with ADP, the aggregation rate is less with adrenaline and collagen 2 mg /ml. The degree of aggregation has increased with the use of collagen, and the aggregation time with adrenaline and collagen. The studying of platelet function is an important link in the laboratory control of spontaneous aggregation, which will limit the appearance of new vascular occlusions in patients with DFS.

Randomized trial of pharmacokinetic and pharmacodynamic effects of 13.2 mg intranasal epinephrine treatment in congestion

BackgroundNasal congestion could affect the absorption of an epinephrine nasal spray (ENS). ObjectiveTo compare the pharmacokinetics of 13.2 mg ENS with nasal congestion vs without congestion and vs intramuscular (IM) treatments. MethodsThis phase I, open-label, 4-period randomized crossover study enrolled 51 healthy adults with seasonal allergies into cohorts that received a single dose of 13.2 mg ENS (NDS1C; Bryn Pharma, Lebanon, New Jersey) administered as 2 consecutive sprays in either opposite nostrils (cohort 1) or the same nostril (cohort 2). Both cohorts received 13.2 mg ENS with and without nasal allergen challenge (NAC), 0.3 mg IM epinephrine by autoinjector, and 0.5 mg IM epinephrine by manual syringe (MS). ResultsThe ENS after NAC resulted in higher extent and peak exposures and more rapid time to maximum plasma concentration vs ENS without NAC and IM treatments. In cohort 1, the maximum observed baseline-adjusted epinephrine plasma concentration (pg/mL) of ENS with NAC, IM autoinjector, IM MS, or ENS without NAC was 458.0, 279.0, 364.2, and 270.1, respectively, and in cohort 2 was 436.3, 228.2, 322.3, and 250.8, respectively. The maximum observed baseline-adjusted epinephrine plasma concentration geometric mean ratio (90% CI) for ENS with NAC vs without NAC in cohort 1 was 170% (123%-234%), and in cohort 2 was 174% (115%-263%). In cohort 1, the time to maximum plasma concentration was 15, 21, 45, and 25 minutes, respectively, and in cohort 2 was 18, 20, 45, and 20 minutes, respectively (P < .01 for ENS with NAC vs IM MS). The postdose mean heart rate and blood pressure remained stable and relatively similar to predose values regardless of plasma epinephrine concentration. Mild nausea and headache were the most common adverse events with ENS. ConclusionThe 13.2 mg ENS with congestion exhibited enhanced absorption vs IM treatments and ENS without congestion and seemed to be well tolerated. There was no clinically impactful relationship between pharmacodynamic effects and plasma epinephrine concentration.

Influence of Jerusalem artichoke tuber as a prebiotic on the nutrient utilization, weaning stress indicators and immunocompetence of crossbred calves during the pre- and post-weaning phases

This study explored the potential prebiotic properties of pulverized Jerusalem artichoke tuber (JAP) in pre- and post-weaned calves. Accordingly, 24 fifteen-day-old calves were randomly assigned to four groups (n = 6). The groups received JAP supplementation at levels of 0 (CON), 1 (JAP1), 2 (JAP2), and 3 (JAP3) percent of dry matter intake (DMI) during the first 60 days of the 120-day experiment. Two 6-days digestion trials were conducted: one during the 4th week of the experiment (pre-wean), and the second during the tenth week (post-wean). Additionally, serum concentrations of cortisol and epinephrine were measured in both the pre- and post-weaning phases to assess the stress levels. Immunocompetence of the calves during both the stages was evaluated through lymphocyte proliferation response. In the pre-weaning phase, the calves supplemented with JAP had better (P < 0.05) protein intake and digestion compared to the control group. In the post-weaning phase, the JAP supplemented groups exhibited significantly (P < 0.05) improved digestibility coefficients for dry matter, organic matter, crude protein, ether extract, and neutral detergent fibre. Although cortisol levels didn't show significant differences (P > 0.05) between the groups during both pre-weaning and post-weaning stages, the post-weaning stage did reveal a significant reduction (P < 0.05) in epinephrine levels in JAP1 compared to the other groups. Additionally, JAP supplementation enhanced (P < 0.05) the calves' response to lymphocyte proliferation during the post-weaning phase. Considering the improved nutrient digestibility, enhanced systemic immunity, and reduced epinephrine levels observed in the JAP supplemented groups, our findings suggest that JAP may have promising potential as a prebiotic for calves.

Direct Umbilical Vein Injection of Epinephrine with Cut-Cord Milking in an Ovine Model of Neonatal Resuscitation.

An umbilical venous catheter (UVC) is the preferred route of epinephrine administration during neonatal resuscitation but requires specialized equipment, expertise, and time. Direct injection of epinephrine into the umbilical vein (UV) followed by milking a ~20 cm segment of cut umbilical cord to flush the epinephrine (DUV + UCM) will lead to a quicker administration and earlier return of spontaneous circulation (ROSC) compared with epinephrine given through a UVC. Eighteen near-term asphyxiated lambs were randomized to receive a low-UVC or DUV + UCM of epinephrine at 0.02 or 0.03 mg/kg doses. A total of 16/18 lambs achieved ROSC with a similar mean (±SEM) time to ROSC [DUV + UCM vs. low-UVC (4.67 ± 0.67 vs. 3.99 ± 0.58 min); p = 0.46]. Two out of ten lambs in the DUV + UCM group required UVC placement for additional epinephrine. The administration of the first dose of epinephrine was similar (DUV + UCM-2.97 ± 0.48 vs. UVC-4.23 ± 0.58 min; p = 0.12). Both methods yielded similar epinephrine concentrations (peak concentrations of 253 ± 63 and 328 ± 80 ng/mL for DUV + UCM and UVC EPI, respectively). DUV + UCM resulted in a ROSC success of 78% following the first epinephrine dose and showed similar epinephrine concentrations to UVC. Clinical studies evaluating DUV + UCM as an alternate route for epinephrine while intravenous access is being established are warranted.

Comparison of the effects of two concentrations of adrenaline (0.33 mg/l versus 1 mg/l) in the irrigation serum for arthroscopic shoulder surgery: protocol of a randomized controlled trial

Background: Controlling bleeding during arthroscopic shoulder surgery helps improve the clarity of the arthroscopic visual field. Adrenaline is considered an effective and safe method to reduce bleeding. Two doses of adrenaline (0.33 mg/l and 1 mg/l) have been evaluated in the literature, but never against each other. Methods: This prospective, double-blind, randomized controlled trial will study the clarity of the visual field using a numerical scale (NS) during rotator cuff surgery on 180 patients across 5 centres. The secondary objectives include: the duration of the operation, volume of saline used, increase in baseline pressure, number of arthropump hyperpressures, mean systolic blood pressure and heart rate, as well as sudden variability. Results: Among the 154 patients in the Clinical Trial Group, 70/154 (45%) continued to have proteinuria, while 84/154 (55%) had no proteinuria (remission) compared to 41 (28%) in remission and 104 (72%) with continued proteinuria in the Usual Care group (p&lt;0.001). Conclusions: This study aims to determine which of the two dosages previously studied in the literature (0.33 mg/l versus 1 mg/l) provides better clarity. Trial Registration Number: 2021-A02773-38.

Impedimetric sensor based on molecularly imprinted polythionine from deep eutectic solvent for epinephrine determination

Deep eutectic solvents have obtained growing interest in analytical chemistry due to opportunities related the green chemistry paradigm, i.e., substitution of organic solvents, application of nontoxic ingredients and minimal quantities of wastes formed in their synthesis and usage. In this work, the advantages of deep eutectic solvents were shown in the development of electrochemical sensor for epinephrine determination. Polythionine molecularly imprinted with epinephrine (PTNMIP) was electrodeposited from natural deep eutectic solvent (NADES) consisted of citric acid, glucose, and water in 1:1:6 molar ratio and tested with standard solutions of epinephrine, pharmaceutical preparations, and artificial samples of biological liquids. Only one drop (100 µL) of the monomer dissolved in NADES was applied for sensor preparation on the platform of screen-printed carbon electrode. Electropolymerization was performed by multiple scanning of the potential. The formation of molecular imprints was confirmed by scanning electron microscopy (SEM) and electrochemical impedance spectroscopy (EIS). After the template removal, the charge transfer resistance of the surface layer depended on the epinephrine concentration in the range from 100 nM to 316 µM (limit of detection 50 nM). Selectivity of the signal was confirmed against serotonin and norepinephrine commonly present in biological liquids. Sensor was successfully tested for the determination of epinephrine in spiked solutions mimicking influence of the plasma electrolytes, serum proteins, and in real saliva samples. The recoveries calculated for 10 μM epinephrine ranged from 98.3 to 102.6%. Insignificant influence of the additives and stabilizers present in medications was eliminated by sample dilution. Impedimetric sensor developed showed good opportunities for further application in clinical diagnostics, pharmacokinetics studies and medication manufacture control.

Exercise accelerates recruitment of CD8+ T cell to promotes anti-tumor immunity in lung cancer via epinephrine

Background and purposeIn recent years, there has been extensive research on the role of exercise as an adjunctive therapy for cancer. However, the potential mechanisms underlying the anti-tumor therapy of exercise in lung cancer remain to be fully elucidated. As such, our study aims to confirm whether exercise-induced elevation of epinephrine can accelerate CD8+ T cell recruitment through modulation of chemokines and thus ultimately inhibit tumor progression.MethodC57BL/6 mice were subcutaneously inoculated with Lewis lung cancer cells (LLCs) to establish a subcutaneous tumor model. The tumor mice were randomly divided into different groups to performed a moderate-intensity exercise program on a treadmill for 5 consecutive days a week, 45 min a day. The blood samples and tumor tissues were collected after exercise for IHC, RT-qPCR, ELISA and Western blot. In addition, another group of mice received daily epinephrine treatment for two weeks (0.05 mg/mL, 200 µL i.p.) (EPI, n = 8) to replicate the effects of exercise on tumors in vivo. Lewis lung cancer cells were treated with different concentrations of epinephrine (0, 5, 10, 20 µM) to detect the effect of epinephrine on chemokine levels via ELISA and RT-qPCR.ResultsThis study reveals that both pre- and post-cancer exercise effectively impede the tumor progression. Exercise led to an increase in EPI levels and the infiltration of CD8+ T cell into the lung tumor. Exercise-induced elevation of EPI is involved in the regulation of Ccl5 and Cxcl10 levels further leading to enhanced CD8+ T cell infiltration and ultimately inhibiting tumor progression.ConclusionExercise training enhance the anti-tumor immunity of lung cancer individuals. These findings will provide valuable insights for the future application of exercise therapy in clinical practice.

The inverted U-shaped relationship between epinephrine and pancreatic ductal adenocarcinoma patients' survival with compensation of lymphocyte.

The relationship between epinephrine and cancer can be dose-dependent in invivo study. Whether it is the same in human body still needs verification. We used frozen human pancreatic ductal adenocarcinoma (PDAC) tissues to detect epinephrine content and analyzed its relationship with survival using the K-M method and Cox regression. Disturbance of blood cell count and C-reactive protein and identification of related potent intermediary factors were also analyzed. K-M plot and Cox regression all showed the inverted U-shaped relationship between epinephrine and PDAC survival. Lymphocyte adjustment can increase the HRs of epinephrine for PDAC death by >10%. Epinephrine played an anti-tumor or pro-tumor effect depending on the specific concentration. Circulating lymphocyte count was elevated and might acted as a compensation pathway to reduce the pro-tumor effect of epinephrine to PDAC.

Proteomic and cardiac dysregulation by representative perfluoroalkyl acids of different chemical speciation during early embryogenesis of zebrafish

Perfluoroalkyl acids (PFAAs) of different chemical speciation were previously found to cause diverse toxicity. However, the toxicological mechanisms depending on chemical speciation are still largely unknown. In this follow-up study, zebrafish embryos were acutely exposed to only one concentration at 4.67 μM of the acid and salt of representative PFAAs, including perfluorooctanoic acid (PFOA), perfluorobutane carboxylic acid (PFBA), and perfluorobutanesulfonic acid (PFBS), till 96 h post-fertilization (hpf), aiming to gain more mechanistic insights. High-throughput proteomics found that PFAA acid and salt exerted discriminative effects on protein expression pattern. Bioinformatic analyses based on differentially expressed proteins underlined the developmental cardiotoxicity of PFOA acid with regard to cardiac muscle contraction, vascular smooth muscle contraction, adrenergic signaling in cardiomyocytes, and multiple terms related to myocardial contraction. PFOA salt and PFBS acid merely disrupted the cardiac muscle contraction pathway, while cardiac muscle cell differentiation was significantly enriched in PFBA acid-exposed zebrafish larvae. Consistently, under PFAA exposure, especially PFOA and PFBS acid forms, transcriptional levels of key genes for cardiogenesis and the concentrations of troponin and epinephrine associated with myocardial contraction were significantly dysregulated. Moreover, a transgenic line Tg (my17: GFP) expressing green fluorescent protein in myocardial cells was employed to visualize the histopathology of developing heart. PFOA acid concurrently caused multiple deficits in heart morphogenesis and function, which were characterized by the significant increase in sinus venosus and bulbus arteriosus distance (SV-BA distance), the induction of pericardial edema, and the decrease in heart rate, further confirming the stronger toxicity of PFOA acid than the salt counterpart on heart development. Overall, this study highlighted the developmental cardiotoxicity of PFAAs, with potency ranking PFOA > PFBS > PFBA. The acid forms of PFAAs induced stronger cardiac toxicity than their salt counterparts, providing an additional insight into the structure-toxicity relationship.

Behavioral and physiological responses of horses to ground-based adaptive horsemanship lessons for veterans with post-traumatic stress disorder (PTSD)

Little literature exists on horses in adaptive horsemanship (AH) despite concerns about their well-being. The study objective was to evaluate behavioral and physiological responses of horses to ground-based AH lessons for veterans with post-traumatic stress disorder (PTSD). Lessons were expected to alter horses’ hormone concentrations, behavior, and muscle activity. Geldings were assigned to AH (n=6; 20.3 ± 1.9 yrs., mean ± SE) or control (CON; stall in arena, n=6; 13.8 ± 1.7 yrs.) conditions for 8-week sessions based on current occupation (AH = equine-assisted services; CON = recreational riding). Plasma cortisol, epinephrine, norepinephrine, and oxytocin concentrations from samples at 0 (start of lesson), 3, 5, 25, and 30 (end) min were determined using assays validated in horses. Surface electromyography (sEMG) (masseter and brachiocephalic; Noraxon, Scottsdale, AZ, USA) and video were recorded continuously. Average rectified values (ARV) and median frequency (MF) were calculated (100 ms) after sEMG data were normalized, rectified, and filtered. The number, number of unique, and duration of stress related behaviors (ethogram) were recorded by three trained (ĸ ≥ 0.7) observers. Data were analyzed with repeated measures ANOVAs (significance P ≤ 0.05) with fixed effects of treatment, time point, week, and their interactions as appropriate and random effect of horse. CON horses had elevated cortisol concentrations (P = 0.0023) at 25 and 30 min. AH horses displayed fewer (P ≤ 0.0491) stress related and unique behaviors. CON horses were described as more (P < 0.0001) anxious, nervous, and stressed than AH horses (calm, comfortable, patient, and relaxed) in qualitative behavior analysis (22 observers). AH horses were less stressed than CON horses.

Patterned Au@Ag nanoarrays with electrically stimulated laccase-mimicking activity for dual-mode detection of epinephrine

Epinephrine (EP) is a crucial neurotransmitter in the central nervous system. However, an abnormal level of EP in biological fluids can lead to various diseases. Therefore, it is essential to rapidly and accurately detect EP content. Herein, electrically stimulated patterned Au@Ag nanoarrays with laccase-mimicking activity were designed for the dual-mode detection of EP concentration. The patterned Au@Ag nanoarrays exhibit excellent electrochemical properties and electrically stimulated laccase-mimicking activity. They provide sensitive electrochemical responses for detecting EP content. Simultaneously, the Au@Ag nanoarrays can catalyze the oxidation of EP, enabling its detection through a colorimetric process. This dual-mode approach achieves the detection of EP content over a wide linear range of 0.5–200 μM, with a low detection limit of 0.152 μM. Furthermore, the utility of these nanoarrays for sensing EP in human serum was evaluated. This work provides a convenient method using patterned nanozyme array for the visible, rapid and accurate detection of EP content. It provides the important implication for the development of portable and reliable on-site analytical instruments.

Cortisol as a cerebral cortex neurons apoptosis regulator in acute phase of ischemic stroke (clinical and pathological study)

In response to ischemic stroke (IS) a natural activation of the stress-realizing system occurs. The features of this activation influence the outcome of the acute period and the prognosis of recovery and can be adjusted. At the same time, the role of the stress-realizing system in the pathogenesis of IS is still unexplored.Objective: to investigate the effect of peripheral blood cortisol concentration on the regulation of apoptosis of neurons of the cerebral cortex in the acute phase of IS.Material and methods. A prospective clinical and pathological study was performed. It included 9 patients with IS in the left middle cerebral artery territory who were admitted to hospital and died in the hyperacute phase of IS and had no infectious complications, allergic reactions or oncological diseases and who did not undergo thrombolysis. The cerebral cortex was examined. Neuron-specific enolase (NSE), protein 53 (p53), caspase 3, caspase 8, Fas receptor (CD95), and Fas apoptotic inhibitory molecule 2 (FAIM2) were determined on the slices using an indirect immunoperoxidase immunohistochemical staining method. A total of 567 microscopic fields were analysed for the group of patients with IS and 63 fields for the control group (three people). Before death, the blood concentrations of sFas, sFasL, cortisol, adrenocorticotropic hormone, adrenaline and norepinephrine were determined by enzyme immunoassay (the control group consisted of 28 people).Results. Significant correlation was found between the proportion of casp3-positive neurons and the concentration of cortisol in peripheral blood in zones 2 (r=0.263; p&lt;0.01) and 3 (r=0.383; p&lt;0.01). In the 2nd zone, significant negative correlation was found with the concentrations of sFas (r=-0.177; p&lt;0.05) and sFasL (r=-0.164; p&lt;0.05); in the 3rd zone, significant positive correlation was found with the ratio of the concentrations of sFasL and sFas (r=0.240; p&lt;0.01). The proportion of Fas-positive neurons in the cerebral cortex correlated significantly with the concentration of the soluble form of this molecule (for the 1st zone – r=0.222, for the 2nd zone – r=0.438, for the 3rd zone – r=0.289; p&lt;0.01) and the ratio of the concentrations of sFasL and sFas (respectively: r=0.231, r=0.266 and r=0.281; p&lt;0.01) in the peripheral blood.Conclusion. Peripheral blood cortisol concentration is a factor that determines the regulation of apoptosis of neurons in the cerebral cortex in the acute phase of IS.