Effect of Beta-Adrenergic Agonist Gynipral on the Radical Activity of Neutrophils in the Blood of Women at Different Stages of Reproduction

In recent years, the idea about the physiological significance of neutrophils, including during pregnancy and childbirth, has evolved significantly. There is an opinion that in the course of pregnancy, the activity of non-specific cellular immunity increases, which, in addition to performing a protective function, forms a mode of contractile activity of the uterus that is optimal for child-bearing. In obstetric practice, in order to reduce uterine hypertonicity in the treatment of miscarriage, β-adrenergic agonists are widely used. However, many aspects of their influence on the mother and the foetus remain insufficiently studied. The aim of this paper was to study the effect of Gynipral (selective β2-adrenergic agonist) on the intensity of latex-induced respiratory burst of venous blood neutrophils in women at different stages of reproduction. Using the chemiluminescence method, we showed for the first time that Gynipral, depending on the stage of reproduction, has multidirectional effect on the latex-induced radical activity of neutrophils in the venous blood of women in vitro. At a low level of radical reaction of neutrophils to latex (in the follicular phase of the cycle, during pregnancy and, which is especially important, during childbirth), Gynipral enhances the oxidative activity of cells; at a high level of radical reaction of neutrophils (during the luteal phase of the cycle and after childbirth), Gynipral inhibits it. It can be assumed that in women, catecholamines (adrenaline) during pregnancy through β2- and/or β3-adrenergic receptors increase the ability of neutrophils to produce activated forms of oxygen, while after delivery they reduce this ability. Such changes in receptor activation may be associated with the phenomenon of switching of β-adrenergic receptor coupling from Gs protein to Gi protein, which is important for regulatory mechanisms. For citation: Polezhaeva T.V., Paturova I.G., Zaytseva O.O., Solomina O.N., Khudyakov A.N., Sergushkina M.I., Dmitrieva S.L., Tsirkin V.I. Effect of Beta-Adrenergic Agonist Gynipral on the Radical Activity of Neutrophils in the Blood of Women at Different Stages of Reproduction. Journal of Medical and Biological Research, 2021, vol. 9, no. 2, pp. 171–181. DOI: 10.37482/2687-1491-Z055

Epidemiology of premature birth and details of medical evacuation in the Tyva Republic and Altai Territory

The aim of the research is to assess the epidemiology of premature birth and measures for organizing medical evacuation of patients from agricultural regions in vast territory of the Tyva Republic and Altay Territory for the period 2015-2019. Material and methods. Th e statistical reports data on the work of obstetric service in the Tyva Republic and Altay Territory for the period 2015-2019 are analyzed. Th e frequency, structure, dynamics of premature birth, features of organizing medical evacuation have been studied. Th e analysis of the information received was carried out using absolute, relative and intensive fi gures. Th e statistical signifi cance of the temporal dynamics of data was assessed using regression analysis with calculation of determination coefficient. Results. The analysis showed that premature birth frequency in two agricultural regions with a vast territory and diff erent nationalities in the Tyva Republic and Altay Territory over the past 5 years has no tendency to decrease (2019 – 6.2 % and 7.1 %, respectively) and the data are comparable with an average Russian indicator (2018 - 6.0 %). Distribution of PB by clinical phenotype and gestational age in the studied territories does not diff er and correspond to global indicators. Th e share of very early premature births (22-27 weeks of gestation) is not more than 7 %. A distinctive feature of Altai Territory in comparison with the Tyva Republic is a rarer (p <0.001) obstetric delivery of patients with PB in obstetric hospitals, level III (63.3 % and 96.8 %, respectively), which is associated with high frequency of late PB (53.1 %) and suffi cient capacity of medical organizations, level II. During medical evacuation in the regions, beta-adrenergic agonist ginipral (95 %) was used for acute tocolysis. Conclusion. Organization of medical evacuation in the Tyva Republic is characterized by more frequent use of air ambulance for patient transportation to obstetric hospital, level III, which is explainable by 7 times lower population density compared to Altay Territory with the same schemes of acute tocolysis.

Drugs used in wheeze associated respiratory infection among children in tertiary care teaching hospital

Background: This study was done to study the drugs used in wheeze associated lower respiratory infected paediatric patients in tertiary care teaching hospital.Methods: Sample size was calculated as 78 and patients were selected based on the inclusion and exclusion criteria. The study was a prospective observational study and conducted in Department of Pediatrics, Rajah Muthiah Medical College and Hospital (RMMCH), Annamalai University.Results: Our study shows that male children (63%) are affected with more than female children (37%). The most frequently prescribed drugs are antibiotics (96%), antipyretics (63%), expectorants and antitussives (54%) followed by beta adrenergic agonist (46%), beta adrenergic agonist with anticholinergic combination (14%) corticosteroids (18%). Our study also shows wheeze associated lower respiratory infection (WALRI) in children were significantly associated with bacterial infections (72%).Conclusions: Our study concluded that antibiotics and antipyretics are the most commonly prescribed drugs for WALRI followed by expectorants and antitussives, beta adrenergic agonist, corticosteroids, beta adrenergic agonist with anticholinergic combination. Most of the treatment strategies are adopted from Standard Treatment Guidelines (STG) and World Health Organisation (WHO). The average number of prescribed drugs per encounter was more than that of WHO standards. The percentage of encounters in which an antibiotics and injections was higher than the ideal WHO standards it leads to anti-microbial resistance and costly forms of drug therapy.

Author Correction: The Beta-adrenergic agonist, Ractopamine, increases skeletal muscle expression of Asparagine Synthetase as part of an integrated stress response gene program

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

P6279Mitochondria targeted catalase overexpression protects against beta-adrenergic receptor mediated cardiac remodeling in mice

Background Beta-adrenergic receptor signaling is widely recognized as a fundamental component in the pathogenesis of chronic heart failure. However, the mechanisms behind beta-adrenergic receptor-mediated remodeling in cardiomyocytes and the myocardium are not fully understood. Oxidative stress has been proposed as a central pathophysiological mediator in cardiovascular disease and heart failure. The triggers and sources of oxidative stress in heart failure remain unclear. In this study we use mice with mitochondria-targeted overexpression of the antioxidant enzyme catalase (mCAT) to link beta-adrenergic receptor-mediated stress to mitochondrial reactive oxidative species (ROS) and the progression of heart failure. Hypothesis Mitochondrial ROS, induced by beta-adrenergic receptor-activation, is a mediator in the progression of the heart failure phenotype. Methods mCAT and wild type mice (n=10) were administered the non-selective beta-adrenergic agonist Isoprotenerol (Iso; 50mg/kg/day) through subcutaneous osmotic pumps for 3 weeks. Hearts were taken for biochemistry (western blotting, qPCR). Cardiomyocytes were isolated and loaded with Fluo-3 AM to study intracellular Ca2+ transients and fractional shortening using confocal line scan microscopy. All experiments were performed in accordance with the Stockholm ethical committee for animal research. Results and conclusions The WT mice displayed an increased heart/body weight ratio following chronic Iso administration. In contrast, mCAT mice displayed resistance to Iso-induced cardiac hypertrophy (p<0.05). Furthermore, chronic Iso exposure in WT mice induced increased ROS-dependent post-translational protein modifications, impaired cardiomyocyte Ca2+ handling and reduced contractility in isolated cardiomyocytes (p<0.05). Cardiomyocytes from mCAT mice did not display the deleterious effects of chronic Iso exposure on cardiomyocyte Ca2+ and contractility. Our study demonstrates that beta-adrenergic receptor stimulation-induced remodeling of the heart, which is similar to what is seen in heart failure, can be prevented by overexpressing catalase in the mitochondria. This indicates an important role of mitochondrial ROS in the link between adrenergic signaling and the development of cardiomyopathy and heart failure. Acknowledgement/Funding Hjärtlungfonden

Quantification of ractopamine residues on and in beef digestive tract tissues

Ractopamine hydrochloride is a commercial beta-adrenergic agonist commonly used as a dietary supplement in cattle production for improved feed efficiency and growth promotion. Currently, regulatory target tissues (as approved in the New Animal Drug Application with Food and Drug Administration) for ractopamine residue testing are muscle and liver. However, other tissues have recently been subjected to testing in some export markets for U.S. beef, a clear disregard for scientific maximum residue limits associated with specific tissues. The overall goal of this study was to develop and validate an LC-MS/MS assay to determine whether detectable and quantifiable levels of ractopamine in digestive tract-derived edible offal items (i.e., abomasum, omasum, small intestine, and reticulum) of cattle resulted from tissue residues or residual ingesta contamination of exposed surfaces of tissues (rinsates). Tissue samples and corresponding rinsates from 10 animals were analyzed for parent and total ractopamine (tissue samples only). The lower limit of quantitation was between 0.03 and 0.66 ppb depending on the tissue type, and all tissue and rinsate samples tested had quantifiable concentrations of ractopamine. The highest concentrations of tissue-specific ractopamine metabolism (represented by higher total vs. parent ractopamine levels) were observed in liver and small intestine. Contamination from residual ingesta (represented by detectable ractopamine in rinsate samples) was only detected in small intestine, with a measured mean concentration of 19.72 ppb (±12.24 ppb). Taken together, these results underscore the importance of the production process and suggest that improvements may be needed to reduce the likelihood of contamination from residual ractopamine in digestive tract-derived edible offal tissues for market.

Ephedrine Analysis in Real Urine Sample via Solvent Bar Microextraction Technique Coupled with HPLC-UV and Chemometrics

Background: Ephedrine, an alpha/beta-adrenergic agonist, is one of the most common doping agents not only among athletes but also the ordinary people, therefore its detection at low trace levels with a sensitive and cost effective method has become a priority to investigate many analytical methods. Objective: In this work, solvent bar microextraction followed by high-performance liquid chromatography (HPLC-UV) was used for extraction and determination of ephedrine at low trace levels from urine samples at optimum condition. Methods: In this study, a designed experiment was carried out using solvent bar microextraction technique, which has been proved to be a green method. This method requires three phases consisting of a donor phase with an alkaline pH, an acceptor phase with an acidic pH, and organic solvent to impregnate the pores of the hollow fiber. The obtained results were used for estimating the optimum ranges for each parameter, analyzing the effect of different parameters, simultaneously. Results: Under optimized circumstances, the preconcentration factor was 129. The calibration curves represented good linearity for urine sample with coefficient estimations higher than 0.9991. The limit of detection and quantitation for ephedrine were 16.7 µg L-1 and 50 µg L-1, respectively. The relative standard deviations of analysis were 3.5% within a day (n=3) and 4.1% between days (n=9). Conclusion: According to the results and previous studies, it can be concluded that the preconcentration factor for ephedrine was the best result ever reported considering selectivity and cost-effectiveness.