Endogenous Epinephrine Research Articles

Presynaptic Adrenoceptors.

Presynaptic α2-adrenoceptors are localized on axon terminals of many noradrenergic and non-noradrenergic neurons in the peripheral and central nervous systems. Their activation by exogenous agonists leads to inhibition of the exocytotic release of noradrenaline and other transmitters from the neurons. Most often, the α2A-receptor subtype is involved in this inhibition. The chain of molecular events between receptor occupation and inhibition of the exocytotic release of transmitters has been determined. Physiologically released endogenous noradrenaline elicits retrograde autoinhibition of its own release. Some clonidine-like α2-receptor agonists have been used to treat hypertension. Dexmedetomidine is used for prolonged sedation in the intensive care; It also has a strong analgesic effect. The α2-receptor antagonist mirtazapine increases the noradrenaline concentration in the synaptic cleft by interrupting physiological autoinhibion of release. It belongs to the most effective antidepressive drugs. β2-Adrenoceptors are also localized on axon terminals in the peripheral and central nervous systems. Their activation leads to enhanced transmitter release, however, they are not activated by endogenous adrenaline.

Rare Event of Anaphylaxis Reaction in a Rabies Post-Exposure Prophylaxis Vaccine: A Case Report

Background. One of the most fatal infectious illnesses, rabies can result in severe symptoms in humans and almost 100% fatality if patients don't receive prompt and sufficient PEP (Post Exposure Prophylaxis). Despite the rarity of allergic responses following rabies immunization, vaccines that protect against infectious illnesses can cause anaphylaxis. Determine if the patient will respond quickly to therapy, pass away in a matter of minutes, or recover on their own as a result of endogenous adrenaline, angiotensin II, and endothelin I secretion. The care of children suffering from anaphylactic shock will be the main topic of this case report. Case Presentation. A six-year-old male patient was admitted to emergency department with shortness of breath, swelling of the whole face and body, gasping for air, and cyanosis of lips, hands, and feet. Previously, the patient was bitten by a dog on the front and right side of his neck 90 minutes prior. He was sent to the community health care facility and administered PEP immediately. It was administered in two ampules without any direct adverse reactions were seen in the following 30-minute observation. Neither previous illnesses nor allergies were reported by his parents. When the patient arrived in emergency room, cyanosis was evident, and he was agitated. Airway was secured using head tilt and chin lift. Oxygen saturation was 60%, thus was given 10 liters/minutes oxygen. He was then given an intramuscular injection of 1:1000 0.3 mg epinephrine and fluid challenge of 300 cc ringer’s lactate solution. Upon reassessing, his vitals sign was not getting better. He had cardiac arrest, resuscitated, but to no avail. Conclusion. During the treatment of rabies, anaphylaxis reactions were inevitable. Post procedure monitoring and emergency management of anaphylaxis reactions must always be prepared to prevent a fatal adverse reaction. Adequate preparation for both equipment and medical personnel is necessary to produce a better outcome. Keywords: Anaphylaxis, Rabies, Post-Exposure Prophylaxis, Vaccine, Children, Case Report

Allosteric modulator potentiates β2AR agonist-promoted bronchoprotection in asthma models.

Asthma is a chronic inflammatory disease associated with episodic airway narrowing. Inhaled β2-adrenergic receptor (β2AR) agonists (β2-agonists) promote - with limited efficacy - bronchodilation in asthma. All β2-agonists are canonical orthosteric ligands that bind the same site as endogenous epinephrine. We recently isolated a β2AR-selective positive allosteric modulator (PAM), compound-6 (Cmpd-6), which binds outside of the orthosteric site and modulates orthosteric ligand functions. With the emerging therapeutic potential of G-protein coupled receptor allosteric ligands, we investigated the impact of Cmpd-6 on β2AR-mediated bronchoprotection. Consistent with our findings using human β2ARs, Cmpd-6 allosterically potentiated β2-agonist binding to guinea pig β2ARs and downstream signaling of β2ARs. In contrast, Cmpd-6 had no such effect on murine β2ARs, which lack a crucial amino acid in the Cmpd-6 allosteric binding site. Importantly, Cmpd-6 enhanced β2 agonist-mediated bronchoprotection against methacholine-induced bronchoconstriction in guinea pig lung slices, but - in line with the binding studies - not in mice. Moreover, Cmpd-6 robustly potentiated β2 agonist-mediated bronchoprotection against allergen-induced airway constriction in lung slices obtained from a guinea pig model of allergic asthma. Cmpd-6 similarly enhanced β2 agonist-mediated bronchoprotection against methacholine-induced bronchoconstriction in human lung slices. Our results highlight the potential of β2AR-selective PAMs in the treatment of airway narrowing in asthma and other obstructive respiratory diseases.

Reperfusion cardiac injury. The role of microvascular obstruction

Microvascular obstruction (MVO) of coronary arteries increases the mortality rate and major adverse cardiac events in patients with acute myocardial infarction (AMI) and percutaneous coronary intervention (PCI). According to preliminary data platelets, inflammation, Ca2+ overload, neuropeptide Y, and endothelin-1 could be involved in the pathogenesis of MVO. Many questions related to the pathogenesis of MVO remain unanswered. The role of endothelial cell damage in the formation of MVO in patients with AMI and PCI is unknown. It is unclear whether nitric oxide (NO) production reduces or decreases sensitivity of smooth muscle cells of coronary arteries to NO in patients with MVO. It was obtained only indirect evidence on the involvement of inflammation in the development of MVO. The role of ROS in the pathogenesis of MVO is not studied. The role of necroptosis and pyroptosis in the pathogenesis of MVO in patients with AMI and PCI is also not studied.The significance of thromboxane A, vasopressin, angiotensin II, and prostacyclin in the formation of MVO is unknown before. It was not obtained conclusive evidence on the involvement of coronary artery spasm in the development of MVO. Correlation analysis of the neuropeptide Y, endothelin-1 levels and the MVO size in patients with AMI and PCI was not performed. It is not clear whether endogenous adrenaline exacerbates MVO or, conversely, prevents MVO.

Sympathetic innervation and endogenous catecholamines in neuromuscular preparations of muscles of different functional profiles

Influence of the sympathetic nervous system on the work of skeletal muscles contractile apparatus is now beyond doubt. However, until recently there was no evidence that the endings of sympathetic nerves can be located in close proximity to the neuromuscular synapses, and there is also no reliable data on how much endogenous adrenaline and noradrenaline can be contained near the synaptic contact in skeletal muscles. In this research, using fluorescent analysis, immunohistochemical and enzyme immunoassays the isolated neuromuscular preparations of three skeletal muscles of different functional profiles and containing different types of muscle fibers were examined. Close contact between the sympathetic and motor cholinergic nerve endings and the presence of tyrosine hydroxylase in this area were demonstrated. Concentrations of endogenous adrenaline and noradrenaline in the solution perfusing the neuromuscular preparation were determined under different modes of its functioning. The effects of α and β adrenoreceptor blockers on the processes of acetylcholine quantal secretion from the motor nerve endings were compared. The data obtained provide evidence for the presence of endogenous catecholamines in the neuromuscular junction region and their role in the modulation of the synaptic function.

Sympathetic Innervation and Endogenous Catecholamines in Neuromuscular Preparations of Muscles with Different Functional Profiles

Influence of the sympathetic nervous system on the work of skeletal muscles contractile apparatus is now beyond doubt. However, until recently there was no evidence that the endings of sympathetic nerves can be located in close proximity to the neuromuscular synapses, and there is also no reliable data on how much endogenous adrenaline and noradrenaline can be contained near the synaptic contact in skeletal muscles. In this research, using fluorescent analysis, immunohistochemical and enzyme immunoassays the isolated neuromuscular preparations of three skeletal muscles of different functional profiles and containing different types of muscle fibers were examined. Close contact between the sympathetic and motor cholinergic nerve endings and the presence of tyrosine hydroxylase in this area were demonstrated. Concentrations of endogenous adrenaline and noradrenaline in the solution perfusing the neuromuscular preparation were determined under different modes of its functioning. The effects of α and β adrenoreceptor blockers on the processes of acetylcholine quantal secretion from the motor nerve endings were compared. The data obtained provide evidence for the presence of endogenous catecholamines in the neuromuscular junction region and their role in modulation of the synaptic function.

How to reduce endogenous adrenaline synthesis in patients with a dysfunctional renal medulla using an APZ-BMZ-DXM combination therapy - a preliminary report

How to reduce endogenous adrenaline synthesis in patients with a dysfunctional renal medulla using an APZ-BMZ-DXM combination therapy - a preliminary report

How to reduce endogenous adrenaline synthesis in patients with a dysfunctional renal medulla by APZ-BMZ-DXM combination therapy - a preliminary report

How to reduce endogenous adrenaline synthesis in patients with a dysfunctional renal medulla by APZ-BMZ-DXM combination therapy - a preliminary report

How to reduce endogenous adrenaline synthesis in patients with a dysfunctional renal medulla by APZ-BMZ-DXM combination therapy - a preliminary report

How to reduce endogenous adrenaline synthesis in patients with a dysfunctional renal medulla by APZ-BMZ-DXM combination therapy - a preliminary report

Эффекты кардиотоксинов кобры на папиллярной мышце и сердце крысы, перфузируемом по Лангендорфу, не связаны с выбросом адреналина

In a study of the effects of cobra cardiotoxins on myocardial tissue, both right ventricular (papillary muscle) and left ventricular contractility (isovolumic recording of left ventricular pulse pressure during Langendorff perfusion of the heart) were assessed. In papillary muscle, both toxins, at a concentration of 5 μg/mL, caused short-term increases in contractility to 200±25% and 171±15% for CTX-1 and CTX-2, respectively, at the point of maximum effect. At the same time, for CTX-1 and CTX-2, the time to peak tension (TPT) increased from 104±2 to 111±2 and from 96±2 to 104±5 ms, the relaxation time to 50%(TR50%) from 64±4 to 70±6 and from 64±6 to 69±7 ms, and the relaxation time to 95%(TR95%) from 163±10 to 190±22 and from 148±16 to 155±20 ms, respectively. This significantly differs from the positive inotropic effect of the β-adrenomimetic isoproterenol (170±31%), which causes acceleration of TPT from 106±5 to 89±4 ms, TR50% from 58±6 to 43±4 ms, and TR95% from 145±15 to 90±14 ms. When the whole heart was exposed to cardiotoxins, an increase in contractility was also observed, followed by its suppression and contracture, in contrast to isoproterenol, which caused a steady increase in contractility coupled with an increase in heart rate. Pretreatment of papillary muscles with the β-blocker propranolol 
 (10 μM) did not prevent the development of cardiotoxin effects, but completely blocked the effects of isoproterenol. Our data indicate that the temporary increase in contractility under the action of cardiotoxins is not associated with the release of endogenous adrenaline, but rather is caused by changes in calcium homeostasis in cardiomyocytes.

Sufentanil: a risk factor for lactic acidosis in patients after heart valve surgery

BackgroundsHyperlactatemia is a common metabolic disorder after cardiac surgery with cardiopulmonary bypass. Epinephrine use has been identified as a potential cause of increased lactate levels after cardiac surgery. Stress can lead to an increase in catecholamines, mainly epinephrine, in the body. Exogenous epinephrine causes hyperlactatemia, whereas endogenous epinephrine released by stress may have the same effect. Opioids are the most effective anesthetics to suppress the stress response in the body. The authors sought to provide evidence through a retrospective data analysis that helps investigate the relationship between intraoperative opioid dosage and postoperative lactic acidosis after cardiac surgery.MethodsThe clinical data of 215 patients who underwent valvular heart surgery with cardiopulmonary bypass from July 2016 to July 2019 were analyzed retrospectively. Blood lactate levels were measured at 0.1 h, 2 h, 4 h, and 8 h after surgery. Patients with continuous increases in lactate levels and lactate levels exceeding 5 mmol/L at two or more time points were included in the lactic acidosis group, whereas the other patients were included in the control group. First, univariate correlation analysis was used to identify parameters that were significantly different between the two groups, and then multivariate regression analysis was conducted to elucidate the independent risk factors for lactic acidosis. Fifty-one pairs of patients were screened by propensity score matching analysis (PSM). Then, lactic acid levels at four time points in both groups were analyzed by repeated measures ANOVA.Resultshe EF (heart ejection fraction) (OR = 0.94, P = 0.003), aortic occlusion time (OR = 10.17, P < 0.001) and relative infusion rate (OR = 2.23, P = 0.01) of sufentanil was an independent risk factor for lactic acidosis after valvular heart surgery. The patients were further divided into two groups with the mean sufentanil infusion rate as the reference point. The data were filtered with PSM (Propensity Score Matching). Lactic acid values in both groups peaked at 4 h after surgery and then declined. The rate of lactic acid decline was significantly faster in the group with a higher sufentanil dosage than in the lower group. The difference was statistically significant (P < 0.05). There was also a significant difference in lactic acid levels at the four time points (0.1 h, 2 h, 4 h and 8 h after surgery) in both groups (P < 0.001).ConclusionThe inadequate intraoperative infusion rate of sufentanil is an independent risk factor for lactic acidosis after heart valve surgery. The possibility of lactic acidosis caused by this factor after cardiac surgery should be considered, which is helpful for postoperative patient management.

Stress hormones kinetics in ventricular fibrillation cardiac arrest and resuscitation: Translational and therapeutic implications.

Knowing the kinetics of endogenous stress hormones during cardiac arrest and cardiopulmonary resuscitation (CRP) will help to optimize personalized physiology-guided treatment. The aim of this study was to examine the dynamic changes in stress hormones in a swine model of ventricular fibrillation (VF) cardiac arrest. Ventricular fibrillation was induced in 10 healthy Landrace/Large White piglets, which were subsequently left untreated for 8 min. All animals were resuscitated according to the 2015 European Resuscitation Council guidelines. The concentration of adrenalin, noradrenalin, and cortisol was measured at baseline and at the 4th and 8th minute of VF-cardiac arrest, as well as at 30-min, 60-min, 24 h and 48 h post-ROSC. By the end of the 4th min of VF, the animals of the ROSC group exhibited significantly higher adrenaline levels compared to those of the no-ROSC group (7264 pg/ml vs. 1648 pg/ml, p = 0.03). Noradrenaline was higher in the ROSC group at the 4th min of VF (3021 pg/ml vs. 1626 pg/ml, p = 0.02). Cortisol levels in the ROSC group were significantly lower by the end of the 8th min of VF [16.25 ng/ml vs. 92.82 ng/ml, p = 0.03]. With a cut-off point of 5970 pg/ml, adrenaline at the 4th min of VF exhibited 100% sensitivity and 80% specificity for predicting ROSC. Higher endogenous adrenaline and lower endogenous cortisol levels were associated with ROSC.

Pharmacokinetics of Single Dose Lidocaine and Epinephrine Following Iontophoresis of the Tympanic Membrane in a Double-Blinded Randomized Trial.

Objective:To evaluate local and systemic safety of bilateral iontophoretic administration of lidocaine with epinephrine or lidocaine alone to the tympanic membrane (TM).Study Design:A randomized, double-blind, two-arm study was conducted at a single center. Healthy adults were randomized to bilateral iontophoretic treatment with 2% lidocaine, 1:100,000 epinephrine, or 2% lidocaine (control). Otoscopy, cranial nerve examination, tympanometry, and audiometry safety evaluations were conducted before and 3-days post-procedure. Systemic safety was evaluated via analysis of vital signs taken before and up to 120 minutes post-iontophoresis, and blood samples collected before and up to 230 minutes post-iontophoresis.Results:Twenty-five subjects were treated with bilateral iontophoresis of either lidocaine and epinephrine (n = 15 subjects) or lidocaine alone (n = 10). Mean plasma epinephrine concentrations for both groups remained within the normal range for endogenous epinephrine. Mean plasma concentrations of lidocaine were not statistically different between groups, ranging from 0.245 to 2.28 ng/ml after administration of lidocaine with epinephrine (immediate post-iontophoresis to 230 min post-iontophoresis), compared with 1.35 to 2.14 ng/ml after administration of lidocaine alone. The presence of epinephrine slowed the systemic absorption of lidocaine. Lidocaine levels (Cmax 2.24 ng/ml) were approximately 2000-fold lower than the threshold for minor lidocaine toxicity. No device-, procedure- or drug-related adverse events were reported.Conclusion:The local and systemic safety of bilateral iontophoretic delivery of 2% lidocaine, 1:100,000 epinephrine to the TM was demonstrated by low plasma levels of drug and absence of both serious and non-serious device-, procedure-, or drug-related adverse events.

Boronic acid-modified polyhedral oligomeric silsesquioxanes on polydopamine-coated magnetized graphene oxide for selective and high-capacity extraction of the catecholamines epinephrine, dopamine and isoprenaline.

Amino-functionalized polyhedral oligomeric silsesquioxanes (POSS-8NH2) were covalently bound to the surface of polydopamine-coated magnetized graphene oxide. It was then reacted with 4-formylphenylboronic acid to prepare a "cubic boronic acid"-bonded magnetic graphene oxide adsorbent. The new adsorbent exhibits better selectivity and much higher adsorption capacity for ortho-phenols over adsorbents where small boronic ligands are directly bound to the surface of the material. It is shown to enable selective and faster enrichment of the catecholamines epinephrine (EP), dopamine (DA) and isoprenaline (IP) with high selectivity over many potential interferents that can occur in urine. The analytes were then quantified by HPLC with fluorometric detection. Under optimal conditions, response is linear (R2 ≥ 0.9907), limits of detection are low (0.54-2.3ng·mL-1), and reproducibility is acceptable (inter- and intra-day assay RSDs of≤10.9%). The method was successfully applied to the determination of endogenous EP and DA and exogenous IP in urine samples. Graphical abstractSchematic of boronic acid (BA)-modified polyhedral oligomeric silsesquioxanes (POSS) on polydopamine-coated magnetized graphene oxide (magGO). The material (magGO@POSS-BA) has good selectivity and higher adsorption capacity to ortho-phenols and can be applied to enrich the catecholamines in urine.

Analysis of endogenous epinephrine and norepinephrine enantiomers in rat plasma and application to a stereoselective pharmacokinetics

Epinephrine and norepinephrine are a class of chiral endogenous catecholamines, which are known as major neurotransmitters. This work described a new LC–MS/MS method coupled with pre-column derivatization, enabling the simultaneous enantiomeric separation of epinephrine and norepinephrine in rat plasma. After protein precipitation procedure, the samples were derivatized with (S)-N-(4-nitrophenoxycarbonyl) phenylalanine methoxyethyl ester, [(S)-NIFE]. The derivatives resolved with good baseline separation on an ACQUITY UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 μm) with mobile phase composed of methanol with 0.2% formic acid in water at a flow rate of 0.2 mL/min. Analysis was performed by multiple reaction monitoring in positive ionization mode. The linear ranges were 1.0–500 ng/mL for epinephrine enantiomers and 1.5–750 ng/mL for norepinephrine enantiomers. The lower limits of quantification for epinephrine and norepinephrine enantiomers were 1.0 and 1.5 ng/mL, respectively. The intra-day and inter-day precision were all less than 10.7% and accuracy ranged from 96.0 to 101.5%. Recoveries for all the analytes were more than 80.3%. The proposed method was successfully applied to simultaneously determine endogenous epinephrine and norepinephrine enantiomers in rat plasma. l-epinephrine and l-norepinephrine were sensitively and accurately quantified while both the d-enantiomers were not detected. Additionally, epinephrine enantiomers were analyzed for stereoselective pharmacokinetics in rats after intravenous administration of racemic epinephrine for the first time. The pharmacokinetic results indicated that the disposition of epinephrine enantiomers was stereoselective and chiral inversion did not occur in rats.

Cardiovascular effects of intravenous colforsin in normal and acute respiratory acidosis canine models: A dose-response study

In acidosis, catecholamines are attenuated, and higher doses are often required to improve cardiovascular function. Colforsin activates adenylate cyclase in cardiomyocytes without beta-adrenoceptor. Here, six beagles were administered colforsin or dobutamine four times during eucapnia (partial pressure of arterial carbon dioxide 35–40 mm Hg; normal) and hypercapnia (ibid 90–110 mm Hg; acidosis) conditions. The latter was induced by CO2 inhalation. Anesthesia was induced with propofol and maintained with isoflurane. Cardiovascular function was measured by thermodilution and a Swan-Ganz catheter at baseline and 60 min after 0.3 μg/kg/min (low), 0.6 μg/kg/min (middle), and 1.2 μg/kg/min (high) colforsin administration. The median pH was 7.38 [range 7.33–7.42] and 7.01 [range 6.96–7.08] at baseline in the Normal and Acidosis conditions, respectively. Endogenous adrenaline and noradrenaline levels at baseline were significantly (P < 0.05) higher in the Acidosis than in the Normal condition. Colforsin induced cardiovascular effects similar to those caused by dobutamine. Colforsin increased cardiac output in the Normal condition (baseline: 3.9 ± 0.2 L/kg/m2 [mean ± standard error], low: 5.2 ± 0.4 L/kg/min2, middle: 7.0 ± 0.4 L/kg/m2, high: 9.4 ± 0.2 L/kg/m2; P < 0.001) and Acidosis condition (baseline: 6.1 ± 0.3 L/kg/m2, low: 6.2 ± 0.2 L/kg/m2, middle: 7.2 ± 0.2 L/kg/m2, high: 8.3 ± 0.2 L/kg/m2; P < 0.001). Colforsin significantly increased heart rate and decreased systemic vascular resistance compared to values at baseline. Both drugs increased pulmonary artery pressure, but colforsin (high: 13.3 ± 0.6 mmHg in Normal and 20.1 ± 0.2 mmHg in Acidosis) may have lower clinical impact on the pulmonary artery than dobutamine (high: 19.7 ± 0.6 in Normal and 26.7 ± 0.5 in Acidosis). Interaction between both drugs and experimental conditions was observed in terms of cardiovascular function, which were similarly attenuated with colforsin and dobutamine under acute respiratory acidosis.

Cystic Fibrosis Transmembrane Conductance Regulator Genotype, Not Circulating Catecholamines, Influences Cardiovascular Function in Patients with Cystic Fibrosis.

Background:Cystic fibrosis (CF) is a genetic disease affecting multiple organ systems of the body and is characterized by mutation in the gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR). Previous work has shown that a single dose of aβ-agonist increases cardiac output (Q) and stroke volume (SV) and decreases systemic vascular resistance (SVR) in healthy subjects. This effect is attenuated in patients with CF; however, the mechanism is unknown. Potential explanations for this decreased cardiovascular response to a β-agonist in CF include inherent cardiovascular deficits secondary to the CFTR mutation, receptor desensitization from prolonged β-agonist use as part of clinical care, or inhibited drug delivery to the bloodstream due to mucus buildup in the lungs. This study sought to determine the effects of endogenous epinephrine (EPI) and norepinephrine (NE) on cardiovascular function in CF and to evaluate the relationship between cardiovascular function and CFTR F508del mutation.Methods:A total of 19 patients with CF and 31 healthy control subjects completed an assessment of Q (C2H2 rebreathing), SV (calculated from Q and heart rate [HR]), Q and SV indexed to body surface area (BSA, QI, and SVI, respectively), SVR (through assessment of Q and mean arterial blood pressure [MAP]), and HR (from 12-lead electrocardiogram [ECG]) at rest along with plasma measures of EPI and NE. We compared subjects by variables of cardiovascular function relative to EPI and NE, and also based on genetic variants of the F508del mutation (homozygous deletion for F508del, heterozygous deletion for F508del, or no deletion of F508del).Results:Cystic fibrosis patients demonstrated significantly lower BSA (CF = 1.71 ± 0.05 m2 vs healthy = 1.84 ± 0.04 m2, P = .03) and SVI (CF = 30.6 ± 2.5 mL/beat/m2 vs healthy = 39.9 ± 2.5 mL/beat/m2, P = .02) when compared with healthy subjects. Cystic fibrosis patients also demonstrated lower Q (CF = 4.58 ± 0.36 L/min vs healthy = 5.71 ± 0.32 L/min, P = .03) and SV (CF = 54 ± 5.5 mL/beat vs healthy = 73.3 ± 4.5 mL/beat, P = .01), and a higher HR (CF = 93.2 ± 3.9 bpm vs healthy = 80.5 ± 2.7 bpm, P < .01) and SVR (CF = 2082 ± 156 dynes*s/cm−5 vs healthy = 1616 ± 74 dynes*s/cm−5, P = .01) compared with healthy subjects. Furthermore, CF patients demonstrated a lower SV (P < .01) corrected for NE when compared with healthy subjects. No significant differences were seen in HR or Q relative to NE, or SVR relative to EPI. Differences were seen in SV (F(2,14) = 7.982, P < .01) and SV index (F(2,14) = 2.913, P = .08) when patients with CF were stratified according to F508del mutation (number of deletions).Conclusions:Individuals with CF have lower cardiac and peripheral hemodynamic function parameters at rest. Furthermore, these results suggest that impairment in cardiovascular function is likely the result of F508del CFTR genotype, rather than receptor desensitization or inhibited drug delivery.

Effect of Vitamin C and Vitamin B1 Combination on Mortality of Sepsis and Septic Shock Patients in Intensive Care Unit

Effect of Vitamin C and Vitamin B1 Combination on Mortality of Sepsis and Septic Shock Patients in Intensive Care Unit Andriamuri Primaputra Lubis, Adhrie Sugiarto, Amir S Madjid Abstract Introduction: Vitamin C is known as antioxidant and an important co-factor for endogenous adrenaline synthesis while vitamin B1 is known for its effect on lactate clearance which helps sepsis and septic shock condition. This study was conducted to investigate the effect of vitamin C and B1 combination on 28-day mortality in sepsis and septic shock patients. Methods: This is an open-label randomized controlled trial at tertiary hospital between July until September 2019. Inclusion criteria were patients aged 18-60 years diagnosed with sepsis and/or septic shock. Exclusion criteria were “do not resuscitate” status and on immunosuppressive medications. Thirty-one patients were divided into intervention group (n=15) and control group (n=16). Intervention group received 1.5 g vitamin C every 6 hours and 200 mg vitamin B1 every 12 hours through 3 days. Control group received 200 mg vitamin B1 every 12 hours for 3 days. The 28-day mortality was documented after the administration. This study used chi-square continuity correction as statistical analysis. Results: The relative risk for survival rate in 28-day mortality was 1.30 times higher for intervention group compared to control group (CI 95% 0.76 – 2.21 p=0.53). The mortality risk in 28 days was also lower in intervention group compared to control group (RR=0.61 CI95% 0.22 – 1.66 p=0.53). Conclusion: combination of vitamin C and B1 was able to lower the risk of 28-day mortality although the result wasnot statistically significant. Full Text: PDF DOI: 10.15640/ijhs.v7n4a2

Epinephrine in Anaphylaxis: Preclinical Study of Pharmacokinetics after Sublingual Administration of Taste-Masked Tablets for Potential Pediatric Use

Epinephrine is a life-saving treatment in anaphylaxis. In community settings, a first-aid dose of epinephrine is injected from an auto-injector (EAI). Needle phobia highly contributes to EAI underuse, leading to fatalities—especially in children. A novel rapidly-disintegrating sublingual tablet (RDST) of epinephrine was developed in our laboratory as a potential alternative dosage form. The aim of this study was to evaluate the sublingual bioavailability of epinephrine 30 mg as a potential pediatric dose incorporated in our novel taste-masked RDST in comparison with intramuscular (IM) epinephrine 0.15 mg from EAI, the recommended and only available dosage form for children in community settings. We studied the rate and extent of epinephrine absorption in our validated rabbit model (n = 5) using a cross-over design. The positive control was IM epinephrine 0.15 mg from an EpiPen Jr®. The negative control was a placebo RDST. Tablets were placed under the tongue for 2 min. Blood samples were collected at frequent intervals and epinephrine concentrations were measured using HPLC with electrochemical detection. The mean ± SEM maximum plasma concentration (Cmax) of 16.7 ± 1.9 ng/mL at peak time (Tmax) of 21 min after sublingual epinephrine 30 mg did not differ significantly (p > 0.05) from the Cmax of 18.8 ± 1.9 ng/mL at a Tmax of 36 min after IM epinephrine 0.15 mg. The Cmax of both doses was significantly higher than the Cmax of 7.5 ± 1.7 ng/mL of endogenous epinephrine after placebo. These taste-masked RDSTs containing a 30 mg dose of epinephrine have the potential to be used as an easy-to-carry, palatable, non-invasive treatment for anaphylactic episodes for children in community settings.

β-Blockers, heart disease and COPD: current controversies and uncertainties

Treating people with cardiovascular disease and COPD causes significant clinician anxiety. β-Blockers save lives in people with heart disease, specifically postinfarction and heart failure. COPD and heart disease frequently coexist...