Adrenergic Effects Research Articles

TDAH : quels sont les effets cardiovasculaires du méthylphénidate et quelles sont les conséquences éventuelles pour la pratique clinique ?

ContextMethylphenidate is the first-line pharmacological treatment for ADHD, and its prevalence continues to grow, with an increase of 116% over the last ten years in France. Its use in hospitals has been extended to neurologists, psychiatrists and pediatricians, and its prescription can be renewed by a general practitioner. Cardiovascular complications are rare, but life-threatening. Management practices currently vary widely from one medical center or doctor to another. ObjectivesReviewing the cardiovascular effects of methylphenidate in adults and children with ADHD, aiming to propose a practical management plan without intending to replace existing recommendations. MethodsThe subject under study aimed to answer the following PICO question “What are the cardiovascular consequences (outcomes) when using MPH (intervention) for an ADHD population (population) regardless of age”. We carried out systematic review of international reviews and meta-analyses, selected using the PRISMA methodology via the PubMed, Cochrane Library and Google Scholar databases. Their methodological quality was assessed using the AMSTAR-2 scale. Cardiovascular events considered were the adrenergic effects of MPH on the cardiovascular system, looking for changes in blood pressure and heart rate, and the serious cardiovascular effects represented by sudden death/arrhythmia, myocardial infarction and stroke. A total of 17 systematic reviews and meta-analyses met the eligibility criteria. ResultsOf the 734 articles found, twelve were finally selected. Four concerned a population of children, five a mixed population of adults and children and three a population of adults only. They included two systematic reviews and ten meta-analyses. Three reviews included cohort studies and nine included randomized controlled trials. Three clinical situations can be distinguished depending on the age of the patient and the length of exposure to methylphenidate. The first, on initiation of treatment, there was a marked by a short-term increase in blood pressure and heart rate. The second involves a patient under the age of 35 with short- to medium-term exposure to MPH. A persistent adrenergic effect tends to increase the risk of sudden death by 12% (if the resting heart rate increases by ten beats per minute). This risk is further increased if the patient has psychiatric comorbidities and their associated treatments, congenital heart disease and uses recreational substances. Finally, the last situation involves a patient exposed to MPH for several years and aged over 35, whose main risk is the onset of atheromatous disease with myocardial infarction and ventricular arrhythmia. In this case, a comprehensive approach is required, identifying risk factors and behavioral factors likely to exacerbate the risk of CV disease. ConclusionsThe short-term cardiovascular effects of MPH are well documented and statistically significant, with a moderate but significant increase in blood pressure (+2mmHg) and heart rate (+5bpm). Longer-term cardiovascular safety data are often lacking, leading to conflicting conclusions. Meta-analyses of cohort studies conclude that there is an increase in cardiovascular risk, while meta-analyses of randomized trials find no significant statistical association. This means that patients and their families need to be made aware of this lack of data. Personalized management based on age, duration of exposure to MPH and the clinical profile of patients as defined by cohort studies seems to us to be the most appropriate approach. In people under 35, the main risk is sudden death. In this population, it is important to identify any congenital heart disease and to look for psychiatric comorbidities, and by assessing the substance abuse. For people over 35, the main risk is coronary heart disease. In this case, a comprehensive approach is required, identifying risk factors and behavioral factors likely to exacerbate the risk of CV disease. Our daily practice is more in line with cohort studies including patients with co-morbidities associated with their ADHD, as well as a significant risk of having risky behaviors, depressive episodes, heart disease and prolonged exposure to MPH and other drugs. Prescribing MPH in this context is tricky, with a higher risk of cardiovascular events. Close clinical monitoring is therefore necessary, and specialist advice may be required.

Effect of Propranolol on Motor Cortex Excitability in Essential Tremor: An Exploratory Study.

Essential tremor, the world's most prevalent movement disorder, lacks a clear understanding of its pathophysiology. Propranolol, a non-specific beta-blocker capable of crossing the blood-brain barrier, is a primary choice for essential tremor treatment. While its tremor-reducing effects are generally attributed to peripheral actions, various uses hint at central adrenergic effects. Nevertheless, propranolol's precise impact on the central nervous system in essential tremor subjects remains unexplored. In this study, we employed transcranial magnetic stimulation to assess the influence of propranolol on the excitability of the primary motor cortex (M1) in patients with essential tremor, compared to an age- and sex-matched control group. Cortical excitability parameters were measured following placebo and propranolol administration, encompassing resting and active motor thresholds, motor evoked potential characteristics, cortical silent period, and the input/output curve. Distinct effects were observed across the two cortical hemispheres. Essential tremor patients displayed inhibition of the left M1 cortex and heightened excitability in the right M1 cortex four hours after propranolol administration, but not following placebo. These findings suggest potential differential noradrenergic excitatory and inhibitory modulation. However, comprehensive understanding necessitates further investigations, including left-handed participants and more diverse essential tremor subpopulations. This study underscores the need for continued exploration to unravel propranolol's complex effects on motor cortex excitability in essential tremor.

Adrenergic effect on women's blood neutrophil oxidative activity the first day after delivery.

Recent studies have described a significant role for neutrophils in reproductive processes and their participation in the preparation of the cervix for childbirth and the activation of labor, in the postpartum involution of the uterus, and in the occurrence of preeclampsia. This study aimed to assess the formation of free radicals by neutrophils in the blood of women on the first day after childbirth and to characterize the adrenergic effect on this process. Venous blood samples from 100 female volunteers aged 26-32 years who had 2 or 3 full-term deliveries were collected and analyzed. Various adrenergic compounds were considered (agonists alphaand betaadrenoreceptors, adrenoblockers). The intensity of the respiratory burst of neutrophils and the effect of adrenergic substances on them were assessed with latex-induced luminol-dependent chemiluminescence. Neutrophil activity depends on the stage of the woman's reproductive process: it decreases during pregnancy, reaches the lowest values during childbirth, and increases significantly in the first hours after childbirth. On the first day after childbirth, alpha-1-adrenergic receptors are highly active in neutrophils, through which NADP-H-oxidase is activated and activated oxygen species are formed. At the same time, alphaor beta-agonists inhibit the radical activity of cells. Latex-induced oxidative burst of female blood neutrophils correlates with the stage of the reproductive process. Stressful conditions in the postpartum period can suppress the ability of neutrophils to release reactive oxygen species, which increases the risk of postpartum infections.

Effect of adrenaline concentration in tumescence solution on intraoperative hemodynamics of liposuction patients: A randomized triple-blind trial

ABSTRACT Background Epinephrine in liposuction solution mediated vasoconstriction thus decrease in adrenergic side effects, local anesthetic toxicity, and bleeding. The optimum safe adrenaline concentration was not well investigated. Aim This study aimed to compare between adrenaline 1 mg/L and 2 mg/L in tumescent fluid concerning hemodynamics during abdominal liposuction operations. Methods Forty cases scheduled for liposuction for abdomen and flanks and body were involved in this randomized, triple-blind, controlled trial. Cases were randomized equally into two groups. Group A (low adrenaline concentration group): received 1 mg per liter of epinephrine. Group B (high adrenaline concentration group): received 2 mg per liter of epinephrine. Results Intraoperative heart rate and mean arterial blood pressure at base line were insignificantly different between both groups (p value > 0.05) while at 30, 60, 90, and end of surgery were significantly higher in group B group as opposed to group A (p value < 0.05). Incidence of sinus tachycardia and PVCs were significantly higher in group B than group A (P < 0.05), while surgeon satisfaction was comparable between both groups (p value > 0.05). Conclusions In liposuction procedures, the safest adrenaline concentration is 1 mg/L as evidenced by hemodynamics stability and surgeon satisfaction thus even in high volume liposuction, the adrenaline concentration should not exceed 1 mg/L and should be handled to cover the used crystalloid solution.

Evaluation of the α&lt;sub&gt;2&lt;/sub&gt;-adrenergic Agonist Mafedine Effects on White Outbred Mouse Behaviour Following Acute Administration

Introduction. α2-adrenergic agonists are not only used as antihypertensive and sedative agents, but are also of interest as potential medications for the treatment of neurological disorders. Previous research has shown a compound from this class, 6-oxo-1-phenyl-2-(phenylamino)-1,6-dihydropyrimidine-4-ol (mafedine), to exert strong neuroprotection under experimental conditions. Despite its long record of development, the effects of mafedine on animal behavioural characteristics remain unknown.Aim. This work was aimed at evaluating the effects of mafedine sodium at three doses (1, 10, or 50 mg/kg) on white outbred mouse behavior in three tests: Open Field, Elevated Plus Maze, and Light/Dark Box.Materials and methods. Experiments were carried out on 60 white outbred male mice weighing 20–22 g, randomized into 4 groups (n = 15): 1) control (0,9 % saline); 2) mafedine (1 mg/kg); 3) mafedine (10 mg/kg); 4) mafedine (50 mg/kg). All agents were administered via single intraperitoneal injections 20 min before testing. Animal behavior was assessed using the Open Field, Elevated Plus Maze, and Light/Dark Box tests following conventional protocols with group reassignment between tests and an inter-test time interval of at least 2 days. Statistical analysis was carried out using the Prism 8.0.2 software package.Results and discussion. At 1 or 10 mg/kg, mafedine did not affect animal behaviour in either of the tests. At 50 mg/kg, it produced an anxiolytic effect, as indicated by the decrease in the anxiety index values for the Elevated Plus Maze test as well as the increase in peeking out frequency in the Light/Dark Box test, compared to respective control values.Сonclusion. Mafedine sodium salt at doses between 1 and 50 mg/kg was shown to produce no adverse effect on mouse behaviour, indicating a good safety profile of the compound. The discovered anxiolytic effect of mafedine at the highest dose validates its further research not only as a neuroprotector, but also as an anti-anxiety agent.

New therapeutic strategy targeting regulation of the SERCA2 complex protects from myocardial ischemia-reperfusion injury

Abstract 7 million people suffer every year from myocardial infarction. There is significant unmet medical need for cardioprotection during MI treatment. The beta-adrenergic receptor/cyclic AMP/protein kinase A (PKA) signalling pathway regulates heart rate and contractility. Activation of cAMP-dependent PKA causes phospholamban (PLB) phosphorylation and its ability to inhibit sarcoplasmic reticulum calcium ATPase (SERCA) is lost. Discrete control of PLB phosphorylation is facilitated by the A-kinase anchoring protein (AKAP) 18g/d, which holds PKA and PLB in close proximity. We are developing a novel drug candidate, named 13M, with a highly selective mechanism of action in cardioprotection currently in pre-clinical phase. Our drug candidate disrupts the AKAP18g/d-PLB protein-protein interaction (PPI) as this may protect from ischemia reperfusion injury (IRI). We used AlphaScreen assay to screen a library of 79,000 small molecular compounds for compounds that disrupted the AKAP18δ-PLB PPI. Following secondary and tertiary screens of sub-libraries, the resulting hits were further characterized and similarity searches carried out to delineate a compound structure for further derivatization. Newly synthesized compounds were further tested in a cell-line based assay to determine compound toxicity. A combination of biochemistry, electrophysiology and heart function experiments demonstrated that the compounds exclusively block the adrenergic effect on SERCA2 without affecting its basal activity. A 40% reduction in infarction size and improved long term cardiac function was observed in an animal disease model for ischemia-reperfusion injury.

Comparative study of Heart Rate variability in pregnant women living in conditions of High-mountain Hypoxia of the Pamirs and the steppe zone of Central Kazakhstan

A comparative analysis of the main indicators of heart rate variability was carried out in 72 women aged 25-35 with a normal course of pregnancy, 90-30 days and 10-5 days before delivery, living in different geographical areas: high-mountainous region of Tajikistan (Pamir, Murghab village, 3600-4200m above sea level) and the steppe region of Central Kazakhstan (546m above sea level). The mechanism of compensatory-adaptive reactions, which is not typical for other regions, was revealed in pregnant women living in conditions of high-altitude hypoxia. In women living in the territory of Central Kazakhstan, at 90-30 days before delivery, pregnancy proceeded against the background of increased activity of the sympathetic division of the autonomic nervous system (SD of ANS). Recovery of heart rate variability (HRV) began 10–5 days before term birth, which is the result of a decrease in the effectiveness of adrenergic effects and an increase in the effectiveness of M-cholinergic effects on heart rate, according to some authors1,2. These changes in HRV can be successfully used as a biological marker of a mother’s readiness for childbirth, taking into account the availability and safety of the HRV method. In Pamir women, an increase in the activity of the parasympathetic division (PD) of ANS was noted 90-30 days before childbirth, and persisted until delivery. Starting from the third trimester of pregnancy, the dynamics of the values of such parameters as AMo (amplitude mode), ARI (autonomic rhythm index), RMSD (root mean square deviation), VR (variation range) showed a optimal functional state of regulatory systems before childbirth. This was also evidenced by the value of the stress index, which was in the range of 194-197 units. This mechanism of regulation in the conditions of high-altitude hypoxia ensures the normal development of the fetus and the mobilization of the functional reserves of newborns during childbirth and after birth.

Ephedramine therapeutic effectiveness for allergic rhinitis treatment: a double blind placebo controlled trial

Background : Allergic rhinitis is a common allergic disease worldwide. To date therewas no curable treatment. Study design: Double blind placebo controlled clinicaltrial. Patients and Methods: Ephedramine was evaluated as treatment for allergicrhinitis. One hundred and twenty subjects were included in the study. The patientswas divided into two groups (A) and (B), given either placebo or ephedramine(acombination of pseudoephedrine HCl 60mg plus chlorpheneramine maleate 2.5mg). The drug was given twice daily for subsequent four weeks. Patients withallergic rhinitis and associated conditions were involved in the study. Results: Ourpatients demonstrate a very well response to ephedramine; 44.8% had completeremission from congestion at the end of trial while 78.8% had remission fromRhinorrhoea, 71.1% remitted from sneezing and 80.4% had complete remission frompruritus. The corresponding values in placebo group were 31.5%, 31.5%, 17.8% and31.4% respectively. Side effects of ephedramine include headache (32.7%), dizziness(27.7%), and dry mouth (21.8%). The same above side effects were reported inplacebo group, but with lower frequency. Conclusion: Ephedramine was effective astreatment for allergic rhinitis and associated conditions with non significant sideeffects and minimized antihistamine effect of chlorpheneramine maleate by -adrenergic effect of pseudoephedrine.

Research Progress in Pathogenesis of Hypertension in Acute Intermittent Porphyria

Acute intermittent porphyria (AIP) has complicated clinical manifestations and is often accompanied by hypertension.AIP may cause hypertension through adrenergic effect,heme deficiency,inflammation,inappropriate secretion of antidiuretic hormone,toxicity of delta-aminolevulinic acid(ALA,aporphyrin precursor),and elevated serum glucose level.The prevention and treatment strategies for AIP accompanied with hypertension mainly include the controlling of porphyria attacks,application of antihypertensive drugs,lifestyle intervention,and management of latent AIP patients.

Abstract P1044: A Drug-Like Activity Of Polydopamine Nanoparticles Mediates Cardiomyocyte Bio-Modulation And Maturation

Introduction: Bio-active nanomaterials are being extensively explored for various biomedical and tissue engineering applications. Polydopamine nanoparticles (PDA-NPs) is a self-assemble polymer derived from dopamine which has demonstrated anti-inflammatory potential by modulating immune cells. The use of PDA-NPs as bio-active nanomaterial for cardiac tissue repair/regeneration warrants further exploration. Hypothesis: We hypothesize that the polydopamine nanoparticles could modulate cardiomyocyte activity due to the presence of catechol moieties and may alter the gene expression and promote maturation of cardiomyocyte. Results: The PDA-NPs were fabricated by oxidative polymerization of dopamine monomers which resulted in formation of spherical nanoparticles. These nanoparticles were in the range of 100- 200 nm as evident from SEM and TEM imaging. The FTIR analysis of PDA-NPs revealed the characteristic peaks confirming the presence of quinone and catechol groups. These functional groups play important role in surface adhesion, thus imparting adhesive properties to PDA-NPs. The PDA-NPs were exposed to human iPSC-derived cardiomyocytes (HiPSC-CMs) and their real-time activity was monitored by using MEA. An instantaneous change in the beat period of cardiomyocytes was observed in a dose dependent manner. Moreover, a significant shortening in field potential duration was also seen, these finding suggest that the PDA-NPs stimulates the cardiomyocytes through catechol groups thereby exhibiting strong adrenergic effect. These finding demonstrates that PDA-NPs could significantly modulate the contractility of cardiomyocytes and could be used for enhancing cardiac contractility. Furthermore, prolonged incubation of PDA-NPs showed accumulation in the perinuclear region as revealed by fluorescence imaging. The influence of intracellular accumulation of PDA-NPs on gene expression was assessed by qRT-PCR. A significant increase in MYL2/MYL7 ratio, GJA5 and TNNI3 was noted, demonstrating the maturation of cardiomyocytes. Conclusion: Overall, the treatment of hiPSC-CMs cardiomyocytes with PDA-NPs shows dual response, primarily by modulating the contractility in a dose dependent manner and secondary by promoting maturation.

Cerebellar Hemorrhage Presented as Torsades de Pointes

&lt;p&gt;A 67-year-old female with a history of hypertension was presented to the emergency department with headache and vomiting. She fell into a coma soon after her arrival and had a cardiac arrest. Cardiopulmonary resuscitation was immediately performed, and epinephrine was given every 3 min. Her initial rhythm was pulseless electrical activity,which later developed into Torsades de Pointes (TdP). However, TdP was misinterpreted as ventricular fibrillation (VF).Amiodarone was given for sustained wide QRS complex arrhythmia. After the return of spontaneous circulation (ROSC),a brain computed tomography scan showed a cerebellar haemorrhage. It may be difficult to distinguish TdP from VF during resuscitation since electrocardiographic artefacts could mislead health care providers. In this case, TdP may be related to catecholamine-induced cardiac injury, brain stem compression or adrenergic effects of epinephrine.Furthermore, this case report emphasises the importance of brain computed tomography for patients who suddenly collapsed in emergency departments; even a lethal arrhythmia was initially noted.&lt;/p&gt; &lt;p&gt;&amp;nbsp;&lt;/p&gt;

Музична терапія в лікуванні хвороби Альцгеймера

Стаття являє собою огляд досліджень, присвячених застосуванню музичної терапії у комплексному лікуванні хвороби Альцгеймера. Аналізуються результати наукових досліджень, опублікованих за останні 5 років у журналах, що індексуються у науково-дослідних базах Scopus, Web of Science, MedLine та PubMed. Аналіз свідчить, що музична терапія позитивно впливає на когнітивні функції пацієнтів із деменцією завдяки здатності стимулювати нейропластичність мозку і холінергічну активність вегетативної нервової системи, посилювати кровообіг головного мозку, ослабляти стрес і патологічні адренергічні впливи. Музична терапія є ефективним та безпечним методом покращення пам’яті, ослаблення депресії, тривоги та ажитації в осіб з хворобою Альцгеймера. Широке використання методу у практичній діяльності неврологічної служби буде сприяти підвищенню ефективності лікування хвороби Альцгеймера.

Hemodynamic Impact of Drug Interactions With Epinephrine and Antipsychotics Under General Anesthesia With Propofol.

Antipsychotic drugs exhibit α-1 adrenergic receptor-blocking activity. When epinephrine and antipsychotic drugs are administered in combination, β-2 adrenergic effects are thought to predominate and induce hypotension. This study aimed to assess hemodynamic parameters in patients regularly taking antipsychotics who were administered epinephrine-containing lidocaine under general anesthesia in a dental setting. Thirty patients taking typical and/or atypical antipsychotics and scheduled for dental procedures under general anesthesia were enrolled. Five minutes after tracheal intubation, baseline systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and percutaneous oxygen saturation (SpO2) measurements were taken. The SBP, DBP, HR, and SpO2 measurements were repeated 2, 4, 6, 8, and 10 minutes after the injection of 1.8 mL of 2% lidocaine (36 mg) with 1:80,000 epinephrine (22.5 mcg) via buccal infiltration. Differences between the baseline measurements and those of each time point were analyzed using Dunnett test, and no statistically significant changes were observed. Our findings demonstrate that the use of epinephrine at a clinically relevant dose of 22.5 mcg for dental treatment under general anesthesia is unlikely to affect the hemodynamic parameters of patients taking antipsychotic medications.

Metabolic resuscitation in pediatric sepsis: a narrative review.

Sepsis, defined as infection with associated organ dysfunction, accounts for most childhood deaths due to infection globally. Evidence for the optimal support of children with septic shock refractory to the initial sepsis management bundle remains minimal. There is an urgent need for more effective interventions. Administration of hydrocortisone in children with septic shock might fasten shock resolution, and has been shown to dampen the systemic host immune response, augment adrenergic effects, and support the stress response. Ascorbic acid (vitamin C) is one of the most powerful naturally occurring antioxidants and has beneficial effects on multiple pathways which are severely deranged during septic shock. A regimen combining hydrocortisone, ascorbic acid, and thiamine termed “metabolic resuscitation” or “HAT therapy” has been tested in large trials in critically ill adults with sepsis with conflicting results. Available information on intravenous ascorbic acid indicates an excellent safety profile even at very high doses both in adults and children. Given the pharmacological properties and beneficial effects shown both in vitro and in animal studies, and its safety profile, ascorbic acid either as a single therapy or as part of HAT treatment represents a promising candidate for future pediatric sepsis treatments. While pediatric age groups may be more susceptible to ascorbic acid deficiency during sepsis, there is a lack of high-quality trial data on HAT therapy in this age group. A single centre retrospective study identified potential for mortality benefit in children with septic shock, and the results from a randomized controlled pilot trial are being awaited. It is imperative for pediatric research on ascorbic acid and HAT in children with sepsis to critically investigate key questions related to pharmacology, dosing, timing, feasibility, safety, effects on short- and long-term outcomes, and generalisability in view of the global burden of sepsis.

Гиперактивный мочевой пузырь – особенности патогенеза и выбора медикаментозной терапии

The information about the founders of studies of the bladder function in our country, the features of the nervous and humoral regulation of the lower urinary tract activity, the cholinergic and adrenergic effects of mediators are presented in the article in the form of a clinical lecture. The pathogenetic features of detrusor dysfunction in overactive bladder and the principles of choosing drug therapy are described. Special attention is paid to the comparative characteristics of modern M-anticholinergics.

Adrenoceptors Modulate Cholinergic Synaptic Transmission at the Neuromuscular Junction.

Adrenoceptor activators and blockers are widely used clinically for the treatment of cardiovascular and pulmonary disorders. More recently, adrenergic agents have also been used to treat neurodegenerative diseases. Recent studies indicate a location of sympathetic varicosities in close proximity to neuromuscular junctions. The pressing question is whether there could be any effects of endo- or exogenous catecholamines on cholinergic neuromuscular transmission. It was shown that the pharmacological stimulation of adrenoceptors, as well as sympathectomy, can affect both acetylcholine release from motor nerve terminals and the functioning of postsynaptic acetylcholine receptors. In this review, we discuss the recent data regarding the effects of adrenergic drugs on neurotransmission at the neuromuscular junction. The elucidation of the molecular mechanisms by which the clinically relevant adrenomimetics and adrenoblockers regulate quantal acetylcholine release from the presynaptic nerve terminals and postsynaptic sensitivity may help in the design of highly effective and well-tolerated sympathomimetics for treating a number of neurodegenerative diseases accompanied by synaptic defects.

Adrenergic Storm Induced Warburg Effect in COVID-19

At present, there is no treatment option available for COVID-19 condition and most importantly the underlying pathophysiology in COVID-19 is not known. In this article, I had given a viewpoint that explains the underlying pathophysiology in COVID-19 and based on it proposed treatment options for COVID-19. I propose that the adrenergic storm-induced Warburg effect (aerobic glycolysis) may be the underlying mechanism in the COVID-19 condition. I propose alpha1 adrenergic blockers in the early phase and beta-adrenergic blockers in the late phase of COVID-19 to inhibit the adrenergic storm and reverse the Warburg effect in COVID-19 condition.

Synephrine in dietary supplements and specialized foodstuffs: biological activity, safety and methods of analysis

Synephrine is a natural protoalkaloid of the bitter orange Citrus aurantium L., it has structural similarity to ephedrine and adrenaline. Synephrine in the form of bitter orange extract is widely used as an ingredient of dietary supplements (DS) and specialized foodstuffs (SF) intended for weight loss and fitness improvement. Along with thermogenic and lipolytic effects, synephrine can cause cardiovascular side effects, especially when combined with caffeine and physical activity. This aspect is important, insofar as the main consumers of weight loss products are overweight people who are at risk of developing cardiovascular diseases. The aim of the research is a hygienic assessment of the usage of bitter orange extract and synephrine in DS and SF, which includes an analysis of approaches to technical regulation in the Russian Federation and abroad, a review of data on biological activity, safety, types of adulteration and methods for the determination of citrus protoalkaloids. Results. The adrenergic effect of bitter orange is caused by the presence of R-(-)-psynephrine, making up about 90% or more of the total protoalkaloids. Dry bitter orange fruit extracts, standardized to synephrine content, which can vary from 4 to 98%, are used in the production of DS and SF. Synephrine is a weak adrenergic agonist, acting primarily through β3-adrenergic receptors, stimulating lipolysis. Because of insufficient safety data, the consumption of synephrine is regulated in the Russian Federation and abroad. The upper permissible level of synephrine consumption in the Russian Federation is 30 mg per day. Various cases of adulteration of DS and SF for weight loss and sport nutrition have been revealed: undeclared addition of synephrine in the form of bitter orange extract, addition of synthetic synephrine, its isomers or analogs. The main method for the determination of synephrine and other biogenic amines in DS and SF is high performance liquid chromatography with ultraviolet and/or mass detection. Conclusion. The data presented in the review confirm the feasibility of developing an official method for determination of main protoalkaloids and monitoring of DS and SF for the content of synephrine and other citrus protoalkaloids on its basis.

Comparison of Combined Nebulization of Salbutamol-Ipratropium Bromide with Salbutamol Alone in Children with Mild and Moderate Acute Asthma

ntroduction: The β2 agonists are potent bronchodilators but their repeated and high doses are related to adrenergic side effects. While ipratropium bromide, an anticholinergic bronchodilator has less adverse effects.&#x0D; Objective: To compare the efficacy of combined nebulization of salbutamol-ipratropium bromide with salbutamol alone in children with mild and moderate acute asthma.&#x0D; Materials and Methods: This randomised control trial was done on 80 children aged 5 to 12 years who presented with mild to moderate acute asthma in the emergency department of Children Hospital of Pakistan Institute of Medical Sciences (PIMS) from July 2014 to June 2016 and randomized into 2 groups. In the experimental group each child received 2 nebulizations of combined salbutamol (5mg) and ipratropium Bromide (0.25mg) at presentation and 20 minutes later. Similarly, each child of the control group received 2 nebulizations of 5mg Salbutamol and 2 ml of Normal saline. Asthma clinical score (ACS) was assessed at baseline and then after every 20 minutes up to one hour after the presentation.&#x0D; Results: In the experimental group, the mean + SD ACS at presentation and 60 minutes were 3.50±1.8 and 3.45±1.7 respectively with mean + SD change in ACS of 0.05 ± 0.1. In the control group, the mean + SD ACS at presentation and 60 minutes were 3.70 ± 1.2 and 3.60 ± 1.9, respectively with mean + SD change in ACS of 0.1 ± 0.7. This difference in mean + SD change in ACS between 2 groups was not statistically significant (P=0.6560).&#x0D; Conclusion: There is no statistically significant benefit of adding ipratropium bromide with salbutamol nebulization as compared to salbutamol alone for the management of children with mild to moderate asthma attacks.

β2 Adrenergic Regulation of the Phagocytic and Microbicide Capacity of Circulating Monocytes: Influence of Obesity and Exercise.

Obese individuals present anomalous immune/inflammatory responses with dysregulations in neuroendocrine responses and immune/stress feedback mechanisms. In this context, exercise and β2 adrenergic activation present monocyte-mediated anti-inflammatory effects that are modulated by obesity. However, these anti-inflammatory effects could immunocompromise the monocyte-mediated innate response against a pathogen challenge. Thus, the objective of this work was to evaluate the effect of obesity, and exercise in this condition, on the β2 adrenergic regulation of the phagocytic and microbicide capacity of circulating monocytes. C57BL/6J mice were allocated to different sedentary or exercised, lean or obese groups. Obese mice showed a lower monocyte-mediated innate response than that of lean mice. Globally, selective β2 adrenergic receptor agonist terbutaline decreased the innate response of monocytes from lean and obese sedentary animals, whereas exercise stimulated it. Exercise modulates β2 adrenergic regulation of the innate response in lean and obese animals, with a global stimulatory or neutral effect, thus abolishing the inhibitory effect of terbutaline occurring in sedentary animals. These effects cannot be explained only by changes in the surface expression of toll-like receptors. Therefore, in general, terbutaline does not hinder the effects of regular exercise, but regular exercise does abolish the effects of terbutaline in sedentary individuals.