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Cellular Physiology and Biochemistry :... May 2024Adrenaline quickly inhibits the release of histamine from mast cells. Besides β2-adrenergic receptors, several in vitro studies also indicate the involvement of...
BACKGROUND/AIMS
Adrenaline quickly inhibits the release of histamine from mast cells. Besides β2-adrenergic receptors, several in vitro studies also indicate the involvement of α-adrenergic receptors in the process of exocytosis. Since exocytosis in mast cells can be detected electrophysiologically by the changes in the membrane capacitance (Cm), its continuous monitoring in the presence of drugs would determine their mast cell-stabilizing properties.
METHODS
Employing the whole-cell patch-clamp technique in rat peritoneal mast cells, we examined the effects of adrenaline on the degranulation of mast cells and the increase in the Cm during exocytosis. We also examined the degranulation of mast cells in the presence or absence of α-adrenergic receptor agonists or antagonists.
RESULTS
Adrenaline dose-dependently suppressed the GTP-γ-S-induced increase in the Cm and inhibited the degranulation from mast cells, which was almost completely erased in the presence of butoxamine, a β2-adrenergic receptor antagonist. Among α-adrenergic receptor agonists or antagonists, high dose prazosin, a selective α1-adrenergic receptor antagonist, significantly reduced the ratio of degranulating mast cells and suppressed the increase in the Cm. Additionally, prazosin augmented the inhibitory effects of adrenaline on the degranulation of mast cells.
CONCLUSION
This study provided electrophysiological evidence for the first time that adrenaline dose-dependently inhibited the process of exocytosis, confirming its usefulness as a potent mast cell-stabilizer. The pharmacological blockade of α1-adrenergic receptor by prazosin synergistically potentiated such mast cell-stabilizing property of adrenaline, which is primarily mediated by β2-adrenergic receptors.
Topics: Animals; Mast Cells; Epinephrine; Rats; Prazosin; Cell Degranulation; Male; Exocytosis; Patch-Clamp Techniques; Adrenergic alpha-1 Receptor Antagonists; Rats, Wistar
PubMed: 38852193
DOI: 10.33594/000000703 -
The Journal of Allergy and Clinical... Jun 2024
Topics: Humans; Anaphylaxis; Perioperative Period; Epinephrine; Drug Hypersensitivity
PubMed: 38851254
DOI: 10.1016/j.jaip.2024.03.044 -
Analytical Chemistry Jun 2024Epinephrine (EP) is an essential catecholamine in the human body. Currently, most EP detection methods are not suitable for in vivo detection due to material...
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.
Topics: Fluorescent Dyes; Humans; Epinephrine; Carbocyanines; Animals; Optical Imaging; Anions; Caenorhabditis elegans; Limit of Detection; Infrared Rays; HeLa Cells; Molecular Structure
PubMed: 38847356
DOI: 10.1021/acs.analchem.4c01309 -
International Journal of Cardiology Sep 2024no-reflow can complicate up to 25% of pPCI and is associated with significant morbidity and mortality. We aimed to compare the outcomes of intracoronary epinephrine and... (Comparative Study)
Comparative Study
BACKGROUND
no-reflow can complicate up to 25% of pPCI and is associated with significant morbidity and mortality. We aimed to compare the outcomes of intracoronary epinephrine and verapamil with intracoronary adenosine in the treatment of no-reflow after primary percutaneous coronary intervention (pPCI).
METHODS
108 STEMI patients had no-reflow during pPCI were assigned into four groups. Group 1, in which epinephrine and verapamil were injected through a well-cannulated guiding catheter. Group 2, in which same drugs were injected in the distal coronary bed through a microcatheter or perfusion catheter. Group 3, in which adenosine was injected through a guiding catheter. Group 4, in which adenosine was injected in distal coronary bed. Primary end point was the achievement of TIMI III flow and MBG II or III. Secondary end point was major adverse cardiovascular and cerebrovascular events (MACCEs) during hospital stay.
RESULTS
The study groups did not differ in their baseline characteristics. Primary end point was achieved in 15 (27.8%) patients in the guide-delivery arm compared with 34 (63%) patients in the local-delivery arm, p < 0.01. However, the primary end point did not differ between the epinephrine/verapamil group and the adenosine group (27 (50%) vs 22 (40.7%), p = 0.334). The secondary end points were similar between the study groups.
CONCLUSION
Local delivery of epinephrine, verapamil and adenosine in the distal coronary bed is more effective in achieving TIMI III flow with MBG II or III compared with their guide-delivery in patients who suffered no-reflow during pPCI. There was no difference between epinephrine/verapamil Vs. adenosine.
Topics: Humans; Verapamil; Male; Female; Adenosine; Epinephrine; Middle Aged; Percutaneous Coronary Intervention; No-Reflow Phenomenon; ST Elevation Myocardial Infarction; Aged; Vasodilator Agents; Treatment Outcome; Prospective Studies
PubMed: 38844092
DOI: 10.1016/j.ijcard.2024.132228 -
Food Research International (Ottawa,... Jul 2024Tropane alkaloids (TAs) are secondary metabolites from weeds that can contaminate cereals and vegetables during harvest. Due to their toxicity, the Regulation (EC)...
Tropane alkaloids (TAs) are secondary metabolites from weeds that can contaminate cereals and vegetables during harvest. Due to their toxicity, the Regulation (EC) 2023/915 sets maximum levels for atropine and scopolamine in cereal-based foods for infants containing millet, sorghum, buckwheat or their derived products. The aim of this study was to evaluate the effect of pH and temperature on the stability of TAs, as possible parameters in thermal processing to mitigate this chemical hazard in cereal-based infant food. The effect of pH (4 and 7) and temperature (80 °C and 100 °C) was assessed in buffer solutions. Also, treatment at 180 °C was performed in spiked and naturally incurred millet flour to assess the effect of high temperature, simulating cooking or drying, on the stability of TAs in the cereal matrix. The fate of 24 TAs was assessed by UHPLC-MS/MS. TAs showed high thermostability, although it was variable depending on the specific compound, pH, temperature and treatment time. In buffer solutions, higher degradation was found at 100 °C and pH 7. In spiked millet flour at 180 °C for 10 min, scopolamine and atropine contents decreased by 25 % and 22 %, similarly to other TAs which also showed a slow thermal degradation. Atropine, scopolamine, anisodamine, norscopolamine, scopine and scopoline were found in naturally contaminated millet flour. Interestingly, naturally incurred atropine was more thermostable than when spiked, showing a protective effect of the cereal matrix on TAs degradation. The present results highlight the need for an accurate monitorization of TAs in raw materials, as this chemical hazard may remain in infant cereal-based food even after intense thermal processing.
Topics: Edible Grain; Hydrogen-Ion Concentration; Infant Food; Tandem Mass Spectrometry; Food Contamination; Tropanes; Temperature; Alkaloids; Humans; Food Handling; Hot Temperature; Atropine; Infant; Chromatography, High Pressure Liquid
PubMed: 38823829
DOI: 10.1016/j.foodres.2024.114439 -
Biomedicine & Pharmacotherapy =... Jul 2024Therapeutic options for Alzheimer's disease are limited. Dual compounds targeting two pathways concurrently may enable enhanced effect. The study focuses on tacrine...
Therapeutic options for Alzheimer's disease are limited. Dual compounds targeting two pathways concurrently may enable enhanced effect. The study focuses on tacrine derivatives inhibiting acetylcholinesterase (AChE) and simultaneously N-methyl-D-aspartate (NMDA) receptors. Compounds with balanced inhibitory potencies for the target proteins (K1578 and K1599) or increased potency for AChE (K1592 and K1594) were studied to identify the most promising pro-cognitive compound. Their effects were studied in cholinergic (scopolamine-induced) and glutamatergic (MK-801-induced) rat models of cognitive deficits in the Morris water maze. Moreover, the impacts on locomotion in the open field and AChE activity in relevant brain structures were investigated. The effect of the most promising compound on NMDA receptors was explored by in vitro electrophysiology. The cholinergic antagonist scopolamine induced a deficit in memory acquisition, however, it was unaffected by the compounds, and a deficit in reversal learning that was alleviated by K1578 and K1599. K1578 and K1599 significantly inhibited AChE in the striatum, potentially explaining the behavioral observations. The glutamatergic antagonist dizocilpine (MK-801) induced a deficit in memory acquisition, which was alleviated by K1599. K1599 also mitigated the MK-801-induced hyperlocomotion in the open field. In vitro patch-clamp corroborated the K1599-associated NMDA receptor inhibitory effect. K1599 emerged as the most promising compound, demonstrating pro-cognitive efficacy in both models, consistent with intended dual effect. We conclude that tacrine has the potential for development of derivatives with dual in vivo effects. Our findings contributed to the elucidation of the structural and functional properties of tacrine derivatives associated with optimal in vivo pro-cognitive efficacy.
Topics: Animals; Tacrine; Cholinesterase Inhibitors; Receptors, N-Methyl-D-Aspartate; Male; Rats; Dizocilpine Maleate; Maze Learning; Cognition; Rats, Wistar; Acetylcholinesterase; Scopolamine; Excitatory Amino Acid Antagonists; Memory
PubMed: 38823278
DOI: 10.1016/j.biopha.2024.116821 -
Experimental Gerontology Aug 2024Chronic stress (CS) is critically involved in the Alzheimer's disease (AD) pathogenesis resulting in cognitive disturbance. Also, amyloid precursor protein (APP) related...
Quercetin ameliorates cognitive deficit, expression of amyloid precursor gene, and pro-inflammatory cytokines in an experimental models of Alzheimer's disease in Wistar rats.
Chronic stress (CS) is critically involved in the Alzheimer's disease (AD) pathogenesis resulting in cognitive disturbance. Also, amyloid precursor protein (APP) related gens, pro-inflammatory cytokines, and stress increases AD-related pathogenesis through increasing APP, all are important players in the development of AD. Herein, we explore the possible neuroprotective and anti-amnestic effect of quercetin (QUER) on cognitive deficits induced by scopolamine (SCOP) in stressed rats. Stress induction was performed by exposed of rats to 2-h chronic restraint stress for 10 days. Then rats were supplemented with QUER (25 mg/kg/day oral gavage, for 1 month). Ratswere submitted to intraperitoneal (i.p.) injection of SCOP (1 mg/kg) during the final 9 days of QUER supplementation to induce dementia like condition. Following the interventions, behavioral tests [elevated plus maze (EPM) and novel object recognition memory (NORM)] was examined to analysis the cognitive functions. Meanwhile, prefrontal cortex (PFC) and hippocampus of brain were used for gene expression and biochemical studies. Also, the plasma corticosterone (CORT) level was measured. We established that administration of QUER ameliorated the SCOP-related memory impairment. Also, QUER decreased stress related anxiety like behaviors in the EPM. QUER also altered the interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels in both PFC and hippocampus of SCOP treated rats in stress and non-stress conditions. We found that QUER increased APP and amyloid precursor-like protein 2 (APLP2) mRNA expression in both non-stress and stressed rats. Also, our findings imply that QUER suppress the effect of SCOP on cognitive functions. Moreover, decreased APP mRNA expression in the hippocampus were observed following pretreatment of rats with QUER in both stress and non-stress groups. Given that decreased amyloid beta (Aβ) expression in the hippocampus of stressed rats, it can be proposed that elevations in APP mRNA expression by QUER activates non-amyloidogenic pathways leading to reduction in Aβ levels. However, our findings indicate that QUER can be a therapeutic candidate, which exerts an anti-amnesic property against SCOP-induced memory decline. On the other hand, prior QUER administration in stress condition could be a promising approach against AD prevention.
Topics: Animals; Quercetin; Alzheimer Disease; Rats, Wistar; Male; Disease Models, Animal; Rats; Cytokines; Hippocampus; Amyloid beta-Protein Precursor; Stress, Psychological; Cognitive Dysfunction; Scopolamine; Neuroprotective Agents; Corticosterone; Prefrontal Cortex; Cognition
PubMed: 38821324
DOI: 10.1016/j.exger.2024.112466 -
Emergencias : Revista de La Sociedad... Jun 2024
Topics: Humans; Emergency Service, Hospital; Psychoses, Substance-Induced; Tropicamide
PubMed: 38818988
DOI: 10.55633/s3me/026.2023 -
BMC Cardiovascular Disorders May 2024Despite their continued use, the effectiveness and safety of vasopressors in post-cardiac arrest patients remain controversial. This study examined the efficacy of... (Meta-Analysis)
Meta-Analysis
BACKGROUND & OBJECTIVE
Despite their continued use, the effectiveness and safety of vasopressors in post-cardiac arrest patients remain controversial. This study examined the efficacy of various vasopressors in cardiac arrest patients in terms of clinical, morbidity, and mortality outcomes.
METHODS
A comprehensive literature search was performed using online databases (MeSH terms: MEDLINE (Ovid), CENTRAL (Cochrane Library), Embase (Ovid), CINAHL, Scopus, and Google Scholar) from 1997 to 2023 for relevant English language studies. The primary outcomes of interest for this study included short-term survival leading to death, return of spontaneous circulation (ROSC), survival to hospital discharge, neurological outcomes, survival to hospital admission, myocardial infarction, and incidence of arrhythmias.
RESULTS
In this meta-analysis, 26 studies, including 16 RCTs and ten non-RCTs, were evaluated. The focus was on the efficacy of epinephrine, vasopressin, methylprednisolone, dopamine, and their combinations in medical emergencies. Epinephrine treatment was associated with better odds of survival to hospital discharge (OR = 1.52, 95%CI [1.20, 1.94]; p < 0.001) and achieving ROSC (OR = 3.60, 95% CI [3.45, 3.76], P < 0.00001)) over placebo but not in other outcomes of interest such as short-term survival/ death at 28-30 days, survival to hospital admission, or neurological function. In addition, our analysis indicates non-superiority of vasopressin or epinephrine vasopressin-plus-epinephrine therapy over epinephrine monotherapy except for survival to hospital admission where the combinatorial therapy was associated with better outcome (0.76, 95%CI [0.64, 0.92]; p = 0.004). Similarly, we noted the non-superiority of vasopressin-plus-methylprednisolone versus placebo. Finally, while higher odds of survival to hospital discharge (OR = 3.35, 95%CI [1.81, 6.2]; p < 0.001) and ROSC (OR = 2.87, 95%CI [1.97, 4.19]; p < 0.001) favoring placebo over VSE therapy were observed, the risk of lethal arrhythmia was not statistically significant. There was insufficient literature to assess the effects of dopamine versus other treatment modalities meta-analytically.
CONCLUSION
This meta-analysis indicated that only epinephrine yielded superior outcomes among vasopressors than placebo, albeit limited to survival to hospital discharge and ROSC. Additionally, we demonstrate the non-superiority of vasopressin over epinephrine, although vasopressin could not be compared to placebo due to the paucity of data. The addition of vasopressin to epinephrine treatment only improved survival to hospital admission.
Topics: Humans; Vasoconstrictor Agents; Treatment Outcome; Out-of-Hospital Cardiac Arrest; Risk Factors; Return of Spontaneous Circulation; Male; Middle Aged; Female; Aged; Time Factors; Cardiopulmonary Resuscitation; Epinephrine; Recovery of Function; Risk Assessment; Vasopressins; Patient Discharge; Adult
PubMed: 38816786
DOI: 10.1186/s12872-024-03962-4 -
Scientific Reports May 2024Dietary trans 10, cis 12-conjugated linoleic acid (t10c12-CLA) is a potential candidate in anti-obesity trials. A transgenic mouse was previously successfully...
Dietary trans 10, cis 12-conjugated linoleic acid (t10c12-CLA) is a potential candidate in anti-obesity trials. A transgenic mouse was previously successfully established to determine the anti-obesity properties of t10c12-CLA in male mice that could produce endogenous t10c12-CLA. To test whether there is a different impact of t10c12-CLA on lipid metabolism in both sexes, this study investigated the adiposity and metabolic profiles of female Pai mice that exhibited a dose-dependent expression of foreign Pai gene and a shift of t10c12-CLA content in tested tissues. Compared to their gender-match wild-type littermates, Pai mice had no fat reduction but exhibited enhanced lipolysis and thermogenesis by phosphorylated hormone-sensitive lipase and up-regulating uncoupling proteins in brown adipose tissue. Simultaneously, Pai mice showed hepatic steatosis and hypertriglyceridemia by decreasing gene expression involved in lipid and glucose metabolism. Further investigations revealed that t10c10-CLA induced excessive prostaglandin E2, adrenaline, corticosterone, glucagon and inflammatory factors in a dose-dependent manner, resulting in less heat release and oxygen consumption in Pai mice. Moreover, fibroblast growth factor 21 overproduction only in monoallelic Pai/wt mice indicates that it was sensitive to low doses of t10c12-CLA. These results suggest that chronic t10c12-CLA has system-wide effects on female health via synergistic actions of various hormones.
Topics: Animals; Female; Fibroblast Growth Factors; Mice, Transgenic; Mice; Linoleic Acids, Conjugated; Corticosterone; Dinoprostone; Glucagon; Epinephrine; Thermogenesis; Male; Lipid Metabolism; Adipose Tissue, Brown; Fatty Liver; Lipolysis; Hypertriglyceridemia; Adiposity
PubMed: 38816541
DOI: 10.1038/s41598-024-63282-7