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 ß-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.

A Biosensor for Simultaneous Detection of Epinephrine and Ascorbic Acid Based on Fe(III)-Polyhistidine-Functionalized Multi-Wall Carbon Nanotube Composites.

Epinephrine (EP) is a very important chemical transmitter in the transmission of nerve impulses in the central nervous system of mammals. Ascorbic acid (AA) is considered to be the most important extracellular fluid antioxidant and has important antioxidant properties in the cell. In this study, a series of transition metal-polyhistidine-carboxylated multi-wall carbon nanotube nanocomposites were synthesized, and their simultaneous catalytic effects on epinephrine and ascorbic acid were investigated. The results showed that nanocomposites based on iron ions had the highest catalytic activity. The prepared biosensor expressed high selectivity toward EP and AA with LOD values of 0.1 µΜ (AA) and 0.01 µΜ (EP), and sensitivity values of 4.18 µA mM-1 with a range of 0.001-5 mM (AA), 50.98 µA mM-1 with a range of 0.2-100 µM (EP), and 265.75 µA mM-1 with a range of 0.1-1.0 mM (EP). Moreover, it showed good stability, good repeatability and high selectivity in real sample detection. This work is a reference for the design of new electrochemical enzyme-free biosensors and the detection of biomarkers.

Catecholamine Derivatives: Natural Occurrence, Structural Diversity, and Biological Activity.

Catecholamines (CAs) are aromatic amines containing a 3,4-dihydroxyphenyl nucleus and an amine side chain. Representative CAs included the endogenous neurotransmitters epinephrine, norepinephrine, and dopamine. CAs and their derivatives are good resources for the development of sympathomimetic or central nervous system drugs, while they also provide ligands important for G-protein coupled receptor (GPCR) research. CAs are of broad interest in the fields of chemical, biological, medical, and material sciences due to their high adhesive capacities, chemical reactivities, metal-chelating abilities, redox activities, excellent biocompatibilities, and ease of degradability. Herein, we summarize CAs derivatives isolated and identified from microorganisms, plants, insects, and marine invertebrates in recent decades, alongside their wide range of reported biological activities. The aim of this review is to provide an overview of the structural and biological diversities of CAs, the regularity of their natural occurrences, and insights toward future research and development pertinent to this important class of naturally occurring compounds.

Discriminative and quantitative analysis of norepinephrine and epinephrine by surface-enhanced Raman spectroscopy with gold nanoparticle suspensions.

Surface-enhanced Raman spectroscopy (SERS) is a powerful analytical technique capable of increasing the Raman signal of an analyte using specific nanostructures. The close contact between those nanostructures, usually a suspension of nanoparticles, and the molecule of interest produces an important exaltation of the intensity of the Raman signal. Even if the exaltation leads to an improvement of Raman spectroscopy sensitivity, the complexity of the SERS signal and the numbers of parameters to be controlled allow the use of SERS for detection rather than quantification. The aim of this study was to develop a robust discriminative and quantitative analysis in accordance with pharmaceutical standards. In this present work, we develop a discriminative and quantitative analysis based on the previous optimized parameters obtained by the design of experiments fixed for norepinephrine (NOR) and extended to epinephrine (EPI) which are two neurotransmitters with very similar structures. Studying the short evolution of the Raman signal intensity over time coupled with chemometric tools allowed the identification of outliers and their removal from the data set. The discriminant analysis showed an excellent separation of EPI and NOR. The comparative analysis of the data showed the superiority of the multivariate analysis after logarithmic transformation. The quantitative analysis allowed the development of robust quantification models from several gold nanoparticle batches with limits of quantification of 32 µg/mL for NOR and below 20 µg/mL for EPI even though no Raman signal is observable for such concentrations. This study improves SERS analysis over ultrasensitive detection for discrimination and quantification using a handheld Raman spectrometer.

Ti3C2TxMXene/nitrogen-doped reduced graphene oxide composite: a high-performance electrochemical sensing platform for adrenaline detection.

Herein, Ti3C2TxMXene/N-doped reduced graphene oxide (MXene/N-rGO) composite was employed as the electrocatalyst to construct a new electrochemical sensing platform for the determination of adrenaline (AD). The MXene/N-rGO was synthesized via a facile one-step hydrothermal method, where ethylenediamine acted as a reducing agent and N source. The doped N in rGO served as a bridge between MXene and rGO through tight hydrogen bonds. Scanning electron microscopy showed that large numbers of MXenes with accordion-like morphology were distributed on the surface of the N-rGO. The MXene/N-rGO composite displayed a synergetic catalytic effect for oxidizing AD, originating from the unique catalytic activity of N-rGO and the large surface area and satisfactory conductivity of MXene. These characteristics of composite material led to a remarkable effect on signal amplification for the detection of AD, with a wide linear range from 10.0 nM to 90.0µM and a low detection limit of 3.0 nM based on a signal to noise ratio of 3. Moreover, the MXene/N-rGO electrode displayed good stability, repeatability, and reproducibility. Additionally, the proposed sensor was successfully applied for voltammetric sensing of AD in urine with recoveries from 97.75% to 103.0%.

True Picomolar Neurotransmitter Sensor Based on Open-Ended Carbon Nanotubes.

Neurotransmitters are important chemicals in human physiological systems for initiating neuronal signaling pathways and in various critical health illnesses. However, concentration of neurotransmitters in the human body is very low (nM or pM level) and it is extremely difficult to detect the fluctuation of their concentrations in patients using existing electrochemical biosensors. In this work, we report the performance of highly densified carbon nanotubes fiber (HD-CNTf) cross-sections called rods (diameter ∼ 69 µm, and length ∼ 40 µm) as an ultrasensitive platform for detection of common neurotransmitters. HD-CNTf rods microelectrodes have open-ended CNTs exposed at the interface with electrolytes and cells and display a low impedance value, i.e., 1050 Ω. Their fabrication starts with dry spun CNT fibers that are encapsulated in an insulating polymer to preserve their structure and alignment. Arrays of HD-CNTf rods microelectrodes were applied to detect neurotransmitters, i.e., dopamine (DA), serotonin (5-HT), epinephrine (Epn), and norepinephrine (Norepn), using square wave voltammetry (SWV) and cyclic voltammetry (CV). They demonstrate good linearity in a broad linear range (1 nM to 100 µM) with an excellent limit of detection, i.e., 32 pM, 31 pM, 64 pM, and 9 pM for DA, 5-HT, Epn, and Norepn, respectively. To demonstrate practical application of HD-CNTf rod arrays, detection of DA in human biological fluids and real time monitoring of DA release from living pheochromocytoma (PC12) cells were performed.

Estimation of available epinephrine dose in expired and discolored autoinjectors via quantitative smartphone imaging.

Epinephrine autoinjectors (EAIs) are important first aid medications for treating anaphylaxis. A 10-fold price increase over the past 12 years and evidence that expired EAIs may still contain significant doses of available epinephrine have motivated interest in the efficacy of expired EAIs as treatments of last resort. Degradation of expired EAIs, which can be caused by improper storage conditions, results in various degrees of discoloration of the epinephrine solution. Previous studies have determined that significant epinephrine remains available in expired EAIs, but these have only considered EAIs that show no discoloration. Here, we investigate the potential for colorimetric estimation of available epinephrine dose based on the degree of discoloration in expired EAIs. The correlation of available epinephrine dose and time since expiration date was poor (r = - 0.37), as determined by an industry standard UHPLC protocol. Visible absorbance of the samples integrated across the range 430-475 nm correlated well with available epinephrine dose (r = - 0.71). This wavelength corresponds to the blue channel of a typical smartphone camera Bayer filter. Smartphone camera images of the EAI solutions in various illumination conditions were analyzed to assign color indices representing the degree of discoloration. Color index of the samples showed similar correlation (|r| > 0.7) with available epinephrine dose as that of visible spectrophotometry. Smartphone imaging colorimetry is proposed as a potential point-of-use epinephrine dose estimator for expired and degraded EAIs. Graphical abstract.

Forced degradation studies of norepinephrine and epinephrine from dental anesthetics: Development of stability-indicating HPLC method and in silico toxicity evaluation.

Injectable solutions containing epinephrine (EPI) and norepinephrine (NE) are not stable, and their degradation is favored mainly by the oxidation of catechol moiety. As studies of these drugs under forced degradation conditions are scarce, herein, we report the identification of their degradation products (DP) in anesthetic formulations by the development of stability-indicating HPLC method. Finally, the risk assessment of the major degradation products was evaluated using in silico toxicity approach. HPLC method was developed to obtain a higher selectivity allowing adequate elution for both drugs and their DPs. The optimized conditions were developed using a C18 HPLC column, sodium 1-octanesulfonate, and methanol (80:20, v/v) as mobile phase, with a flow rate of 1.5 mL/min, UV detection at 199 nm. The analysis of standard solutions with these modifications resulted in greater retention time for EPI and NE, which allow the separation of these drugs from their respective DPs. Then, five DPs were identified and analyzed by in silico studies. Most of the DPs showed important alerts as hepatotoxicity and mutagenicity. To the best of our acknowledgment, this is the first report of a stability-indicating HPLC method that can be used with formulations containing catecholamines.

Tailoring the CeO2 morphology and its electrochemical reactivity for highly sensitive and selective determination of dopamine and epinephrine.

Four CeO2 nanomaterials with the morphologies of a nanoplate (CeO2-p), a nanocube (CeO2-c), a porous triangular microplate (CeO2-t), and of a porous hierarchical rod-stacked nanobundle (CeO2-b) were synthesized using a hydrothermal method. They were characterized by scanning and transmission electron microscopies, X-ray diffraction and X-ray photoelectron spectroscopy. Electrochemical characterizations reveal the tuning of their morphology and the presence of exposed crystal planes of CeO2 that can be realized by changing the alkali sources. Among these materials, the CeO2-b features the largest specific surface and lowest electron transfer resistance towards the redox probe Fe(CN)63-/4-. The best voltammetric response to dopamine and epinephrine is thus achieved by using the Nafion-CeO2-b coated electrode. A sensitive and selective method was developed that can voltammetrically detect dopamine (with a peak near 0.13 V vs. SCE), and epinephrine (with a peak near 0.25 V vs. SCE). The detection limits are 2.9 and 0.67 nM, respectively. Graphical abstractSchematic representation of morphology tailoring of CeO2 and electrochemical sensing of dopamine and epinephrine on these CeO2 samples with different morphologies.

ß-Adrenoceptor Activation in Breast MCF-10A Cells Induces a Pattern of Catecholamine Production Similar to that of Tumorigenic MCF-7 Cells.

Adrenaline, which participates in the neuroendocrine response that occurs during stress and perimenopause, may be tumorigenic. This exploratory study aimed at investigating whether non-tumorigenic and tumorigenic human breast epithelial cell lines are able to synthesize adrenaline. The study was carried out in non-tumorigenic (MCF-10A) and tumorigenic (MCF-7) human breast cell lines. Expression of enzymes involved in adrenaline synthesis was characterized by RT-qPCR, immunocytochemistry and western blot. Catecholamines and analogue compounds were quantified by HPLC-ECD. Functional assessment of the impact of drugs on cells' tumorigenic potential was assessed by determination of cell viability and clonogenic ability. Both MCF-10A and MCF-7 cells produce catecholamines, but the capacity to produce adrenaline is lower in MCF-10A cells. ß-adrenoceptor activation increases the capacity of MCF-10A cells to produce adrenaline and favor both cell viability and colony formation. It is concluded that exposure of human breast epithelial cells to ß-adrenoceptor agonists increases cell proliferation and the capacity to produce adrenaline, creating an autocrine potential to spread these adrenergic effects in a feed-forward loop. It is conceivable that these effects are related to tumorigenesis, bringing a new perspective to understand the claimed anticancer effects of propranolol and the increase in breast cancer incidence caused by stress or during perimenopause.

Amplified electrochemiluminescence signals promoted by the AIE-active moiety of D-A type polymer dots for biosensing.

Three-component conjugated polymers of a strong donor-acceptor (D-A) type could be synthesized by Pd-catalyzed Suzuki coupling polymerization reaction of 1,2-bis(4-bromophenyl)-1,2-diphenylethene (M-1) with 9-octyl-3,6-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9H-carbazole (M-2) and 4,6-bis((E)-4-bromostyryl)-2,2-difluoro-5-phenyl-2H-1l3,3,2l4-dioxaborinine (M-3). Among them, P-1 and P-2 with high TPE ratios at 0.95 and 0.9 showed obvious aggregation-induced emission (AIE) behavior; in contrast P-3 with a low TPE ratio at 0.8 showed an aggregation-caused quenching (ACQ) phenomenon. In particular, the three resulting polymer dots (P-1 to P-3 Pdots) exhibited a 200 mV lower electrochemiluminescence (ECL) potential due to their strong D-A electronic structure. Most importantly, the ECL signals of Pdots could be enhanced as high as 3 times by increasing their AIE-active TPE moiety ratios from 0.8 (P-3) to 0.95 (P-1) via the band gap emission process. Herein, P-1 Pdots with the strongest ECL signal were successfully used as ECL biosensors for the detection of catechol, epinephrine and dopamine with detection limits of 1, 7 and 3 nM, respectively. This work provides a new strategy for developing highly sensitive ECL biosensors by the smart structure design of the AIE-active Pdots.

Antidepressive Effects of Taraxacum Officinale in a Mouse Model of Depression Are Due to Inhibition of Corticosterone Levels and Modulation of Mitogen-Activated Protein Kinase Phosphatase-1 (Mkp-1) and Brain-Derived Neurotrophic Factor (Bdnf) Expression.

BACKGROUND Depression is a common disorder linked with high levels of chronicity, psycho-social and physical problems, and suicide. Here, we assessed the antidepressant effects of the hydromethanolic extract of Taraxacum officinale and investigated the underlying mechanism. MATERIAL AND METHODS Antidepressant effects were examined by use of the tail suspension test (TST). Concentrations of corticosterone, dopamine, noradrenaline, and adrenaline were examined by biochemical assays. The mRNA expression was assessed by quantitative RT-PCR. Phytochemical analysis was performed by LC/MS. RESULTS The results showed that the extract at the dosage of 50 and 100 mg/kg significantly (p<0.01) alleviated the TST-induced immobility in the mice, and the effects were comparable to the antidepressant drug Bupropion, which was used as the positive control. Investigation of the underlying mechanism revealed that the T. officinale extract exerts it effects by significantly (p<0.05) decreasing the levels of corticosterone and increasing the concentrations of dopamine, noradrenaline, and adrenaline. Further, the extract also increased the expression of brain-derived neurotrophic factor (Bdnf), which was associated with significant (p<0.05) decrease in the expression of mitogen-activated protein kinase phosphatase-1 (Mkp-1), indicative of the antidepressant potential of T. officinale. Finally, the active constituents of the extract, which include isoetin, hesperidin, naringenin, Kaempferol, sinapinic, and gallic acid, were also identified, which could potentially be responsible for its antidepressant effects. CONCLUSIONS In conclusion, T. officinale exerts significant antidepressant effects in a mouse model of depression by inhibition of corticosterone levels and modulation of Mkp-1 and Bdnf expression.

Fast Cyclic Square-Wave Voltammetry To Enhance Neurotransmitter Selectivity and Sensitivity.

Although fast-scan cyclic voltammetry (FSCV) has been widely used for in vivo neurochemical detection, the sensitivity and selectivity of the technique can be further improved. In this study, we develop fast cyclic square-wave voltammetry (FCSWV) as a novel voltammetric technique that combines large-amplitude cyclic square-wave voltammetry (CSWV) with background subtraction. A large-amplitude, square-shaped potential was applied to induce cycling through multiple redox reactions within a square pulse to increase sensitivity and selectivity when combined with a two-dimensional voltammogram. As a result, FCSWV was significantly more sensitive than FSCV ( n = 5 electrodes, two-way ANOVA, p = 0.0002). In addition, FCSWV could differentiate dopamine from other catecholamines (e.g., epinephrine and norepinephrine) and serotonin better than conventional FSCV. With the confirmation that FCSWV did not influence local neuronal activity, despite the large amplitude of the square waveform, it could monitor electrically induced phasic changes in dopamine release in rat striatum before and after injecting nomifensine, a dopamine reuptake inhibitor.

Neurotransmitters in hermatypic coral, Acropora spp., and its contribution to synchronous spawning during reproductive event.

Synchronous spawning as mass reproduction is well known to occur in many hermatypic corals, which is one of the mysterious life birth events. However, its contributing mechanism has not yet been clarified. This study placed focus on elucidating a neurotransmitter as endocrine signals that contribute to the synchronous spawning. First, the determination method of the neurotransmitters in coral was established by LC/MS in the selective ion mode together with a solid phase extraction method. As a result, the similar contents of the neurotransmitters for dopamine (DA), adrenaline (AD) and noradrenaline (NR) were detected in both the hermatypic corals of Acropora intermedia and Acropora digitifera. More interestingly, these neurotransmitters increased through the reproductive event during the synchronous spawning of A. intermedia, particularly, remarkable changes in the NR and DA were observed. In addition, hydrogen peroxide is known as the spawning stimulant and the metabolic by-product of the neurotransmitters, which was exposed to A. digitifera, then the neurotransmitters increased as well as those of the synchronization of spawning. All of the results suggested that the neurotransmitters contribute to the synchronous spawning in the hermatypic corals.

A novel fluorescent biosensor for adrenaline detection and tyrosinase inhibitor screening.

In this work, a novel simple fluorescent biosensor for the highly sensitive and selective detection of adrenaline was established. Firstly, water-soluble CuInS2 quantum dots (QDs) capped by L-Cys were synthesized via a hydrothermal synthesis method. Then, the positively charged adrenaline was assembled on the surface of CuInS2 QDs due to the electrostatic interactions and hydrogen bonding, which led to the formation of adrenaline-CuInS2 QD (Adr-CuInS2 QD) electrostatic complexes. Tyrosinase (TYR) can catalyze adrenaline to generate H2O2, and additionally oxidize the adrenaline to adrenaline quinone. Both the H2O2 and the adrenaline quinone can quench the fluorescence of the CuInS2 QDs through the electron transfer (ET) process. Thus, the determination of adrenaline could be facilely achieved by taking advantage of the fluorescence "turn off" feature of CuInS2 QDs. Under the optimum conditions, the fluorescence quenching ratio If/If0 (If and If0 were the fluorescence intensity of Adr-CuInS2 QDs in the presence and absence of TYR, respectively) was proportional to the logarithm of adrenaline concentration in the range of 1 × 10-8-1 × 10-4 mol L-1 with the detection limit of 3.6 nmol L-1. The feasibility of the proposed biosensor in real sample assay was also studied and satisfactory results were obtained. Significantly, the proposed fluorescent biosensor can also be utilized to screen TYR inhibitors. Graphical abstract Schematic illustration of the fluorescent biosensor for adrenaline detection (A) and tyrosinase inhibitor screening (B).

Comprehensive characterization of neurochemicals in three zebrafish chemical models of human acute organophosphorus poisoning using liquid chromatography-tandem mass spectrometry.

There is a growing interest in biological models to investigate the effect of neurotransmitter dysregulation on the structure and function of the central nervous system (CNS) at different stages of development. Zebrafish, a vertebrate model increasingly used in neurobiology and neurotoxicology, shares the common neurotransmitter systems with mammals, including glutamate, GABA, glycine, dopamine, norepinephrine, epinephrine, serotonin, acetylcholine, and histamine. In this study, we have evaluated the performance of liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the multiresidue determination of neurotransmitters and related metabolites. In a first step, ionization conditions were tested in positive electrospray mode and optimum fragmentation patterns were determined to optimize two selected reaction monitoring (SRM) transitions. Chromatographic conditions were optimized considering the chemical structure and chromatographic behavior of the analyzed compounds. The best performance was obtained with a Synergy Polar-RP column, which allowed the separation of the 38 compounds in 30 min. In addition, the performance of LC-MS/MS was studied in terms of linearity, sensitivity, intra- and inter-day precision, and overall robustness. The developed analytical method was able to quantify 27 of these neurochemicals in zebrafish chemical models for mild (P1), moderate (P2), and severe (P3) acute organophosphorus poisoning (OPP). The results show a general depression of synaptic-related neurochemicals, including the excitatory and inhibitory amino acids, as well as altered phospholipid metabolism, with specific neurochemical profiles associated to the different grades of severity. These results confirmed that the developed analytical method is a new tool for neurotoxicology research using the zebrafish model.

Expired Epinephrine Maintains Chemical Concentration and Sterility.

OBJECTIVES: Epinephrine shortages affect nearly all American emergency medical services (EMS) systems. Utilization of expired epinephrine could mitigate this situation in daily EMS operations. Concerns about using expired medications include sterility, potency, and potential harmful chemical decay byproducts. There are no cross-platform analyses of sterility and chemical purity of multiple samples of expired parenteral epinephrine. We hypothesized that epinephrine injections will remain sterile and will retain their active ingredient's content for more than 30 months past expiration. METHODS: Six parenteral epinephrine prefilled syringes, 1 mg/10 mL, with an expiration date of January 1, 2012 had been stored in the climate controlled setting of a hospital inpatient pharmacy where they remained until they were taken for chemical or microbial analysis 30 months after expiration. An unexpired parenteral epinephrine prefilled syringe content was used as a control. Contents of three separate syringes with expired content from the same lot and one control underwent ultra-high pressure liquid chromatography-mass spectrometry (UHPLC-MS) and nuclear magnetic resonance (NMR) to determine epinephrine content and stability. In parallel, contents of another three expired epinephrine syringes were analyzed for sterility by plating on aerobic, anaerobic, and fungal media in a hospital microbiology laboratory. The aerobic plates were checked for growth in 3 days, the anaerobic in 5 days, and the fungal in 28 days. RESULTS: UHPLC-MS and NMR showed that content of epinephrine present in the original sample remained unchanged compared to the control. There was no statistical difference in the UHPLC-MS and NMR signal amplitudes between the control and the expired samples. No chemical degradation byproducts were detected using NMR. There was no growth of any bacteria or fungus. CONCLUSION: Recurrent epinephrine shortages impact EMS and hospital operations in the United States. Individual administrators may be hesitant to authorize use of expired pharmaceuticals due to perceived potential complications or fear of litigation. This study shows that the original parenteral epinephrine remains sterile and detectably pure more than 2.5 years after expiration. Further study of the sterility and chemical integrity of expired medications that had been subjected to the conditions of EMS vehicles may be a future research endeavor based on the aforementioned paradigm.

Simultaneous voltammetric sensing of acetaminophen, epinephrine and melatonin using a carbon paste electrode modified with zinc ferrite nanoparticles.

A highly selective electrochemical sensor was fabricated based on a modified carbon paste electrode with zinc ferrite nanoparticles (ZnFe2O4 NPs). The nanocomposite has attractive properties such as high surface-to-volume ratio and good electrocatalytic activity towards the drugs acetaminophen (AC), epinephrine (EP), and melatonin (MT), best at working voltages of 0.35, 0.09 and 0.55 V (vs. Ag/AgCl), respectively. The linear ranges (and detection limits) are 6.5-135 (0.4) µmol L-1 for AC, 5-100 (0.7) µmol L-1 for EP, and 6.5-145 (3) µmol L-1 for MT. Graphical abstract A novel electrochemical sensor based on a modified carbon paste electrode with zinc ferrite nanoparticles (ZnFe2O4) for the simultaneous detection of the acetaminophen, epinephrine and melatonin was fabricated.

Epinephrine in irrigation fluid for visual clarity in arthroscopic shoulder surgery: a systematic review and meta-analysis.

PURPOSE: To investigate whether epinephrine in irrigation fluid improves visual clarity in arthroscopic shoulder surgery. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) that compared the surgical outcomes of patients who did and did not receive epinephrine during arthroscopic shoulder surgery. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase for relevant RCTs. We used the Cochrane Collaboration's tool to assess the risk of bias and adopted random-effects model meta-analysis to combine data. We used the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology to evaluate the overall quality of the body of the retrieved evidence. The primary outcome was visual clarity. The secondary outcomes were operative time, amount of irrigation fluid, the need for increased pump pressure, and adverse cardiovascular events. RESULTS: This study included three RCTs with a total of 238 participants (124 in the epinephrine group and 114 in the non-epinephrine group). The use of epinephrine in irrigation fluid for shoulder arthroscopy achieved better visual clarity (standardized mean difference, 1.01; 95% confidence interval [CI] 0.63 to 1.39; p < 0.0001) and less need for increased pump pressure (risk ratio, 0.40; 95% CI 0.25 to 0.64; p = 0.0001) compared to the non-epinephrine group. No significant differences were noted in operative time (mean difference - 5.08; 95% CI - 14.46 to 4.31; p = 0.29) and amount of irrigation fluid (mean difference - 1.04; 95% CI - 2.38 to 0.39; p = 0.12) between the two groups. No adverse events were recorded in any of the included trials. CONCLUSIONS: The current evidence shows that the use of epinephrine in arthroscopic shoulder surgery may improve visualization and does not appear to have any major disadvantages. LEVEL OF EVIDENCE: Level I.

[The hormonal indices of hypophysis-adrenal glands system in combatants during missions to "trouble spots".]

The officials of the Interior Ministry of Russia usually perform their duties in extreme and quite often emergency conditions. The hypophysis-adrenal glands system of regulation mainly contributes into supporting formation of mechanisms of compensation of these exposures. The purpose of study is to analyze alterations of content of adrenocorticotropic hormone, cortisol, adrenaline and noradrenaline in officials of the Interior Ministry sent on a mission to territories with local military conflict (the Northern Caucasus) to support public order. The study results demonstrated that during first two months of mission a significant increasing of level of analyzed hormones occurs. This is a proper reaction to changed conditions of environment. These alterations correspond to main propositions of the general adaptation syndrome theory. However, further observation in dynamics of mission established presence of signs of imbalance of secretion of hormones in hypophysis-adrenal glands system. The long-lasting conserving high content of both of adrenocorticotropic hormone and cortisol till the end of mission was established. At the same time, content of hormones of "fast response" to extreme factors of environment (adrenaline, noradrenaline) occurred to be as higher as at the beginning of mission. Such occurrences result in disorder of regulation of inter hormonal relationships that correspondingly is a factor of decreasing of vital stress resistance of organism. The main directions of organizational medical character are proposed within th framework of activities supporting resistance of organism to conditions of extreme impact of emergency situations and decreasing risk of development of pathological conditions.