Epinephrine and norepinephrine are widely used to treat cardiovascular collapse during resuscitation with lipid emulsions in the treatment of drug toxicity including local or non-local anesthetics. The effect of the lipid emulsion Intralipid on the vasoconstriction induced by epinephrine or norepinephrine is, however, still unknown. In this study, the interaction of epinephrine and norepinephrine with the intravenous Intralipid emulsion was investigated by capillary electromigration techniques. Capillary electrokinetic chromatography was performed to determine the distribution coefficients by running the analytes under different experimental conditions (temperature, ionic strength, and pH) through a capillary filled with the background electrolyte containing Intralipid emulsion. In addition, the binding constants of the epinephrine and norepinephrine complexes with Intralipid emulsion were determined based on the effective electrophoretic mobility data obtained by electrokinetic chromatography at a wide concentration range of Intralipid emulsion. The obtained binding constants, as well as the distribution coefficients determined by electrokinetic chromatography, confirm that epinephrine and norepinephrine are hydrophilic compounds and that they are minimally distributed into the Intralipid emulsion. Therefore, their application as drugs for vasoconstriction upon Intralipid emulsion treatment is well motivated.
- Keywords
- Intralipid, binding constant, distribution coefficient, electrokinetic chromatography, lipid emulsion,
- MeSH
- Epinephrine * chemistry MeSH
- Chromatography, Micellar Electrokinetic Capillary * MeSH
- Emulsions chemistry MeSH
- Phospholipids * chemistry MeSH
- Hydrogen-Ion Concentration MeSH
- Norepinephrine * chemistry MeSH
- Soybean Oil MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Epinephrine * MeSH
- Emulsions MeSH
- Phospholipids * MeSH
- Norepinephrine * MeSH
- Soybean Oil MeSH
- soybean oil, phospholipid emulsion MeSH Browser
Surgical operations are intricate and invasive procedures that require continuous monitoring of the patient's biochemical profile. Point-of-care testing would allow healthcare professionals to identify abnormalities and make the necessary interventions to minimize the risk of complications and ensure patient safety. To this end, we report the development of a disposable and compact fully 3D-printed electrochemical cell incorporated into a medical scalpel (Lab-on-a-Scalpel), aiming to promote on-site (electro)chemical analysis in the operating theater. This multifunctional device minimizes the number of instruments needed during surgery and can be fabricated on-demand by using a desktop-sized 3D printer at a very low cost. The performance of the Lab-on-a-Scalpel sensing device was evaluated over various electrochemical techniques (cyclic voltammetry, amperometry, and differential pulse voltammetry) and different setups (stirring, drop-volume analysis, polarization potentials, etc.) for the determination of epinephrine. Results showed attractive analytical figures-of-merit, with the limit of detection (LOD) reaching 0.13 μM, and high accuracy in recovery studies conducted on artificial blood samples. Our findings suggest that Lab-on-a-Scalpel is a valuable tool that enables near-patient diagnostics with a minimum sample volume and holds promise to become an essential tool for robotic-assisted surgery.
- MeSH
- Printing, Three-Dimensional * MeSH
- Epinephrine * analysis blood MeSH
- Electrochemical Techniques * instrumentation MeSH
- Lab-On-A-Chip Devices * MeSH
- Humans MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Epinephrine * MeSH
G protein-coupled estrogen receptor 1 (GPER-1) has gained recognition for its role in conferring cardioprotection. However, the extent to which GPER-1 exerts equally important effects in both sexes remains unclear. The study found similar expressions of GPER-1 in rat heart apex in both sexes. In male rats, administering epinephrine (Epi) at a dose of 31.36 microg/100 g resulted in a rapid decline in cardiac function, accompanied by a sharp increase in bax/bcl-2 levels. In contrast, female rats did not display significant changes in cardiac function under the same conditions. Additionally, compared to the injection of Epi alone (at a dose of 15.68 microg/100 g), the administration of G15 (GPER-1 antagonist) further decreased cardiac function in both male and female rats. However, it only increased mortality and lung coefficient in male rats. Conversely, G1 (GPER-1 agonist) administration improved cardiac function in both sexes. Notably, the apex of the male heart exhibited lower levels of inhibitory G protein (Galphai). Furthermore, female and male rats treated with Epi displayed elevated phosphorylated protein kinase B (p-Akt). Compared to their respective Epi groups, the administration of G15 increased p-Akt levels in female rat hearts but decreased them in male rat hearts. Conversely, the administration of G1 decreased p-Akt levels in females but rapidly increased them in male rats. Our study uncovers the vital role of GPER-1 in protecting against stress-induced heart injuries in a sex-specific manner. These findings hold immense potential for advancing targeted cardiac therapies and enhancing outcomes for both females and males.
- MeSH
- Epinephrine MeSH
- Stress, Physiological physiology MeSH
- Rats MeSH
- Sex Characteristics MeSH
- Rats, Sprague-Dawley * MeSH
- Proto-Oncogene Proteins c-akt * metabolism MeSH
- Receptors, Estrogen metabolism MeSH
- Receptors, G-Protein-Coupled * metabolism MeSH
- Sex Factors MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Epinephrine MeSH
- Gper1 protein, rat MeSH Browser
- Proto-Oncogene Proteins c-akt * MeSH
- Receptors, Estrogen MeSH
- Receptors, G-Protein-Coupled * MeSH
BACKGROUND: Adrenaline-producing tumors are mostly characterized by a sudden release of catecholamines with episodic symptoms. Noradrenergic ones are usually less symptomatic and characterized by a continuous overproduction of catecholamines that are released into the bloodstream. Their effects on the cardiovascular system can thus be different. The aim of this study was to determine the prevalence of cardiovascular complications by catecholamine phenotype. METHODS: We retrospectively analyzed data on the prevalence of cardiovascular events in 341 consecutive patients with pheochromocytoma and paraganglioma treated from 1995 to 2023. Biochemical catecholamine phenotype was determined based on plasma or urinary catecholamines and metanephrines. RESULTS: According to the phenotype, 153 patients had noradrenergic pheochromocytoma and paraganglioma and 188 had adrenergic pheochromocytoma and paraganglioma. In the whole sample, the incidence of serious cardiovascular complications was 28% (95 patients), with no difference between the phenotypes or sexes. The noradrenergic phenotype had significantly more atherosclerotic complications (composite end point of type 1 myocardial infarction and symptomatic peripheral artery disease; odds ratio, 3.58 [95% CI, 1.59-8.83]; P=0.003), while the adrenergic phenotype more often had type 2 myocardial infarction and takotsubo-like cardiomyopathy (OR, 0.24 [95% CI, 0.09-0.57]; P=0.002). These changes remained even after adjustment for conventional risk factors of atherosclerosis. CONCLUSIONS: We found a 28% incidence of cardiovascular complications in a consecutive group of patients with pheochromocytoma and paraganglioma. Patients presenting with a noradrenergic phenotype have a higher incidence of atherosclerotic complications, while the adrenergic phenotype is associated with a higher incidence of acute myocardial damage due to takotsubo-like cardiomyopathy.
- Keywords
- blood pressure, catecholamines, myocardial infarction, paraganglioma, pheochromocytoma,
- MeSH
- Adrenergic Agents MeSH
- Atherosclerosis * complications MeSH
- Phenotype MeSH
- Pheochromocytoma * diagnosis MeSH
- Myocardial Infarction * MeSH
- Cardiomyopathies * MeSH
- Catecholamines MeSH
- Humans MeSH
- Metanephrine MeSH
- Adrenal Gland Neoplasms * pathology MeSH
- Paraganglioma * complications MeSH
- Retrospective Studies MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Adrenergic Agents MeSH
- Catecholamines MeSH
- Metanephrine MeSH
A carbon-carbon linkage is created when a methyl group is implanted on dUMP, thus resulting in the formation of dTMP by thymidylate synthase. The methyl group is deleted by aromatase when androgens are converted to estrogens. The methyl group is rearranged with the help of vitamin B12 in the isomerization of methylmalonyl-CoA to succinyl-CoA. S-adenosylmethionine (SAM) serves as the universal methyl donor involved in the biosynthesis of adrenaline and creatine(phosphate). It also interferes with the 5'-mRNA capping and the degradation of catecholamines (i.e. adrenaline, noradrenaline). Cholesterol could be viewed as a conglomeration of methyl groups. Finally, as part of valine, two methyl functions participate in the origin of one of the most frequent hereditary diseases on earth, sickle cell anemia.
- Keywords
- Adrenaline, Aromatase, Capping of mRNA, Catecholamines, Cholesterol biosynthesis, Creatine(phosphate), Isomerization, Methylmalonyl-CoA -> succinyl-CoA, S-adenosylmethionine (SAM), Sickle cell anemia, Thymidylate synthase, Vitamin B(12),
- MeSH
- Epinephrine MeSH
- Cholesterol * MeSH
- Vitamin B 12 * metabolism MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
- Names of Substances
- Epinephrine MeSH
- Cholesterol * MeSH
- Vitamin B 12 * MeSH
Methoxamine (Mox) is a well-known α1-adrenoceptor agonist, clinically used as a longer-acting analogue of epinephrine. 1R,2S-Mox (NRL001) has been also undergoing clinical testing to increase the canal resting pressure in patients with bowel incontinence. Here we show, that Mox hydrochloride acts as an inhibitor of base excision repair (BER). The effect is mediated by the inhibition of apurinic/apyrimidinic endonuclease APE1. We link this observation to our previous report showing the biologically relevant effect of Mox on BER - prevention of converting oxidative DNA base damage to double-stranded breaks. We demonstrate that its effect is weaker, but still significant when compared to a known BER inhibitor methoxyamine (MX). We further determined Mox's relative IC 50 at 19 mmol L-1, demonstrating a significant effect of Mox on APE1 activity in clinically relevant concentrations.
- Keywords
- apurinic/apyrimidinic endonuclease APE1, base excision repair, methoxamine, α1-adrenoceptor agonist,
- MeSH
- Epinephrine * MeSH
- Receptors, Adrenergic MeSH
- Endonucleases MeSH
- Humans MeSH
- Methoxamine MeSH
- DNA Repair * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Epinephrine * MeSH
- Receptors, Adrenergic MeSH
- Endonucleases MeSH
- Methoxamine MeSH
INTRODUCTION: The analysis of urinary catecholamine metabolites is a cornerstone of neuroblastoma diagnostics. Currently, there is no consensus regarding the sampling method, and variable combinations of catecholamine metabolites are being used. We investigated if spot urine samples can be reliably used for analysis of a panel of catecholamine metabolites for the diagnosis of neuroblastoma. METHODS: Twenty-four-hour urine or spot urine samples were collected from patients with and without neuroblastoma at diagnosis. Homovanillic acid (HVA), vanillylmandelic acid (VMA), dopamine, 3-methoxytyramine, norepinephrine, normetanephrine, epinephrine and metanephrine were measured by high-performance liquid chromatography coupled with fluorescence detection (HPLC-FD) and/or ultra-performance liquid chromatography coupled with electrospray tandem mass spectrometry (UPLC-MS/MS). RESULTS: Catecholamine metabolite levels were measured in urine samples of 400 neuroblastoma patients (24-hour urine, n = 234; spot urine, n = 166) and 571 controls (all spot urine). Excretion levels of catecholamine metabolites and the diagnostic sensitivity for each metabolite were similar in 24-hour urine and spot urine samples (p > .08 and >.27 for all metabolites). The area under the receiver-operating-characteristic curve (AUC) of the panel containing all eight catecholamine metabolites was significantly higher compared to that of only HVA and VMA (AUC = 0.952 vs. 0.920, p = .02). No differences were observed in metabolite levels between the two analysis methods. CONCLUSION: Catecholamine metabolites in spot urine and 24-hour urine resulted in similar diagnostic sensitivities. The Catecholamine Working Group recommends the implementation of spot urine as standard of care. The panel of eight catecholamine metabolites has superior diagnostic accuracy over VMA and HVA.
- Keywords
- catecholamine metabolites, diagnostic sensitivity, metanephrines, neuroblastoma, tandem mass spectrometry, urine collection,
- MeSH
- Chromatography, Liquid methods MeSH
- Homovanillic Acid urine MeSH
- Vanilmandelic Acid urine MeSH
- Humans MeSH
- Metanephrine urine MeSH
- Neuroblastoma * diagnosis MeSH
- Tandem Mass Spectrometry * methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 3-methoxy-4-hydroxymandelic acid MeSH Browser
- Homovanillic Acid MeSH
- Vanilmandelic Acid MeSH
- Metanephrine MeSH
BACKGROUND: Oral squamous cell carcinoma (OSCC) severely affects the quality of life and the 5-year survival rate is low. Exploring the potential miRNA-mRNA regulatory network and analyzing hub genes and clinical data can provide a theoretical basis for further elucidating the pathogenesis of OSCC. METHODS: The miRNA expression datasets of GSE113956 and GSE124566 and mRNA expression datasets of GSE31056, GSE37991 and GSE13601 were obtained from the Gene Expression Omnibus databases. The differentially expressed miRNAs (DEMs) and mRNAs (DEGs) were screened using GEO2R. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by DAVID database. The PPI network was established through STRING database and the hub genes were preliminarily screened out by Cytoscape software. After identifying the hub genes in the TCGA database, we predicted the potential DEM transcription factors, constructed a miRNA-mRNA regulatory network, and analyzed the relationship between the hub genes and clinical data. RESULTS: A total of 28 DEMs and 764 DEGs were screened out, which were composed of 285 up-regulated genes and 479 down-regulated genes. Enrichment analysis showed that up-regulation of DEGs were mainly enriched in extracellular matrix organization and cancer-related pathway, while down-regulation of DEGs were mainly enriched in muscular system process and adrenaline signal transduction. After preliminary screening by PPI network and identification in TCGA, the up-regulated FN1, COL1A1, COL1A2, AURKA, CCNB1, CCNA2, SPP1, CDC6, and down-regulated ACTN2, TTN, IGF1, CAV3, MYL2, DMD, LDB3, CSRP3, ACTA1, PPARG were identified as hub genes. The miRNA-mRNA regulation network showed that hsa-miR-513b was the DEM with the most regulation, and COL1A1 was the DEG with the most regulation. In addition, CDC6, AURKA, CCNB1 and CCNA2 were related to overall survival and tumor differentiation. CONCLUSIONS: The regulatory relationship of hsa-miR-513b/ CDC6, CCNB1, CCNA2 and the regulatory relationship of hsa-miR-342-5p /AURKA were not only verified in the miRNA-mRNA regulatory network but also related to overall survival and tumor differentiation. These results indicated that they participated in the cellular regulatory process, and provided a molecular mechanism model for the study of pathogenesis.
- Keywords
- bioinformatics, oral squamous cell carcinoma (OSCC), regulatory network,
- MeSH
- Epinephrine MeSH
- Aurora Kinase A genetics metabolism MeSH
- Squamous Cell Carcinoma of Head and Neck * genetics MeSH
- Gene Regulatory Networks MeSH
- Quality of Life MeSH
- Humans MeSH
- RNA, Messenger genetics metabolism MeSH
- MicroRNAs * genetics MeSH
- Mouth Neoplasms * genetics MeSH
- PPAR gamma genetics metabolism MeSH
- Gene Expression Regulation, Neoplastic MeSH
- Gene Expression Profiling MeSH
- Transcription Factors genetics MeSH
- Computational Biology methods MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Epinephrine MeSH
- Aurora Kinase A MeSH
- RNA, Messenger MeSH
- MicroRNAs * MeSH
- PPAR gamma MeSH
- Transcription Factors MeSH
Older adults, especially men and/or those with diabetes, hypertension, and/or obesity, are prone to severe COVID-19. In some countries, older adults, particularly those residing in nursing homes, have been prioritized to receive COVID-19 vaccines due to high risk of death. In very rare instances, the COVID-19 vaccines can induce anaphylaxis, and the management of anaphylaxis in older people should be considered carefully. An ARIA-EAACI-EuGMS (Allergic Rhinitis and its Impact on Asthma, European Academy of Allergy and Clinical Immunology, and European Geriatric Medicine Society) Working Group has proposed some recommendations for older adults receiving the COVID-19 vaccines. Anaphylaxis to COVID-19 vaccines is extremely rare (from 1 per 100,000 to 5 per million injections). Symptoms are similar in younger and older adults but they tend to be more severe in the older patients. Adrenaline is the mainstay treatment and should be readily available. A flowchart is proposed to manage anaphylaxis in the older patients.
- Keywords
- COVID-19 vaccines, adrenaline, anaphylaxis, older (adults/people),
- MeSH
- Epinephrine MeSH
- Anaphylaxis * etiology prevention & control MeSH
- COVID-19 * MeSH
- Humans MeSH
- SARS-CoV-2 MeSH
- Aged MeSH
- COVID-19 Vaccines MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Epinephrine MeSH
- COVID-19 Vaccines MeSH
The study investigated the effects of sperm sorting, capacitation treatment and co-cultivation on sexed bovine in vitro embryo production. The effect of treatment and co-culture on production of embryos of the preferred sex from unsorted sperm was also studied. Sperm from five breeding bulls was used for fertilization of mature oocytes as follows: Experiment 1, sorted and unsorted sperm (bulls A-E) treated only with heparin in standard co-cultures; Experiment 2, sorted sperm (bulls A-E) treated with heparin-PHE (penicillamine, hypotaurine, and epinephrine) or heparin-caffeine in drop co-cultures; and Experiment 3, unsorted sperm (bull E) treated with either heparin-PHE or heparin-caffeine in both standard and drop co-cultures. In all bulls, treatment with heparin resulted in significantly (p < .05) reduced cleavage and blastocyst rates from sorted sperm, as compared with those from unsorted sperm. In bulls A, B, D and E, treatment of sorted sperm with heparin-PHE in drops significantly increased the blastocyst rate (p < .05). In unsorted sperm of bull E, heparin-PHE treatment in drops resulted in the XX/XY sex ratio inverse to that obtained by heparin-caffeine treatment in standard co-cultures (32.3%/67.7% and 66.7%/33.3%, respectively). In conclusion, the treatment of sorted sperm with heparin-PHE in modified drop co-cultures can be recommended for production of in vitro sexed embryos. The use of unsorted sperm for production of embryos of the preferred sex by selected capacitation treatment and co-culture can be the method of choice in bulls with low IVF yields from sorted sperm.
- Keywords
- IVF, breeding bulls, capacitation treatment, sexed embryos, sorting, sperm,
- MeSH
- Epinephrine pharmacology MeSH
- Fertilization in Vitro methods veterinary MeSH
- Heparin pharmacology MeSH
- Coculture Techniques methods veterinary MeSH
- Embryo Culture Techniques veterinary MeSH
- Oocytes MeSH
- Penicillamine pharmacology MeSH
- Sex Preselection methods veterinary MeSH
- Cattle MeSH
- Spermatozoa drug effects MeSH
- Taurine analogs & derivatives pharmacology MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Cattle MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Epinephrine MeSH
- Heparin MeSH
- hypotaurine MeSH Browser
- Penicillamine MeSH
- Taurine MeSH