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Background: Vagal nerve denervation during the heart transplant procedure results in higher resting heart rates in these recipients compared to the general population. Relative bradycardia (RB) is a common and often temporary post-operative complication that can be managed with agents like terbutaline; however, little data exist on the efficacy, safety, and necessity of long-term terbutaline use post-heart transplant., Methods: This was a single-center, retrospective, descriptive study conducted at a large academic medical center investigating oral terbutaline use for RB management in heart transplant recipients. Outcomes included time to and reason for terbutaline discontinuation post-transplant, adverse event rates, and permanent pacemaker (PPM) placement rates., Results: In the 229 patients included, the median (IQR) time to terbutaline initiation was 8 (5, 12) days post-heart transplant, with a median (IQR) time to discontinuation of 56 (20, 96) days from the first dose. In most cases, terbutaline was successfully tapered off outpatient due to the resolution of RB. Tachyarrhythmias occurred in 29 (12.7%) patients without long-term sequelae. At 3 months post-transplant, PPM had been placed for chronotropic support in 15 patients (6.6%) with a median time (IQR) to PPM placement of 24 (19, 77) days from transplant., Conclusion: This study's overall low PPM placement rate suggests that early sinus node dysfunction can be treated with pharmacotherapy without committing to a permanent device, and that terbutaline can be used safely in early post-heart transplant recipients. If patients require long-term chronotropic support, the risk-benefit of PPM placement versus continued terbutaline should be considered., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Frequent detection of terbutaline in wastewater highlights its potential risks to human health associated in the environment. Exposure to terbutaline through contaminated water sources or food chain have adverse effects to human health. This work emphasized on the removal of terbutaline from wastewater using adsorption technology. Mechanochemically synthesized [Cu(INA) 2 ] metal-organic frameworks (MOFs) and its magnetic composite ([Cu(INA) 2 ]-MOF@Fe 3 O 4 ) are designed with higher specific surface areas and tailored features to accommodate the molecular size and structure of terbutaline. Thus, batch experiment has been conducted using the [Cu(INA) 2 ]-MOF and [Cu(INA) 2 ]-MOF@Fe 3 O 4 for the terbutaline adsorption. The adsorption efficiency achieved by the MOFs was 91.8% and 99.3% for the Cu(INA) 2 ]-MOF and [Cu(INA) 2 ]-MOF@Fe 3 O 4 respectively. The optimum for the adsorption study included terbutaline concentration of 40 mg/L, adsorbent dose of 5 mg/L, pH of 11, temperature of 25 °C and equilibrium time of 40 min. The kinetics and isotherms have been described by pseudo-second order and Langmuir models, while the thermodynamics revealed the exothermic and spontaneous nature of the process. The promising performance of the MOFs is manifested on the ease of regeneration and reusability, achieving adsorption efficiency of 85.0% and 94.7% by the Cu(INA) 2 ]-MOF and [Cu(INA) 2 ]-MOF@Fe 3 O 4 , respectively at five consecutive cycles. The higher performance of the MOFs demonstrates their excellent potentialities for the terbutaline adsorption from the aqueous solution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Pediatric critical asthma, or formerly known as status asthmaticus, is a common pediatric condition encountered in emergency departments, hospital wards, and pediatric intensive care units. Systemic corticosteroids and inhaled bronchodilators are evidence-based, initial treatments for patients with pediatric critical asthma. If clinical symptoms do not improve, pediatric practitioners often prescribe adjunctive medications including inhaled anticholinergics, intravenous ketamine, intravenous magnesium, intravenous short acting beta 2 agonists, and intravenous methylxanthines (such as aminophylline). In this narrative review, we will summarize the current evidence and present the research gaps related to these therapies in the pediatric population., (Copyright © 2024 by Daedalus Enterprises.)

Recently, the diagnosis of autism spectrum disorder (ASD) has increased from 1 in 150 to every 1 in 36 children in the United States, warranting a need for novel prevention and therapeutic strategies. Broad-spectrum cannabidiol oil, free from delta-9-tetrahydrocannabinol, the psychoactive component of cannabis, may be one such therapeutic. It has a high safety profile and is frequently used as a complementary and integrative intervention by persons experiencing symptoms of anxiety, stress, and inflammation. Using a neurodevelopmental rat model of ASD (based on neuroinflammation induced by stress and terbutaline exposure during pre- and postnatal development), we sought to prevent the development of ASD-like behaviors in male offspring by administering broad-spectrum cannabidiol oil to dams throughout pregnancy (10 mg/kg, i.p., daily, embryonic days 3-16). To assess an ASD-like phenotype in the offspring, we used three behavioral measures relevant to three core ASD symptoms: 1) social communication (time spent vocalizing when alone); 2) repetitive behavior (marbles buried during a marble burying test); and 3) social interaction (time spent interacting with a novel conspecific during the three-chamber social interaction test). Broad-spectrum cannabidiol oil given during pregnancy decreased scores for all three ASD-related behavioral responses, resulting in an overall significant prevention of the ASD-like phenotype. These findings highlight the potential of broad-spectrum cannabidiol oil as a complementary and integrative approach for prevention of stressor-induced sequelae relevant to development of an ASD-like phenotype., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Objective: To describe the clinical course and treatment of 3 dogs with peripheral vasopressor extravasation., Case Series Summary: Although vasopressor extravasation (VE) is a well-documented complication in human medicine, literature describing VE and its management in veterinary patients is sparse. VE increases patient morbidity by causing local tissue injury and necrosis. The gold standard treatment for VE, phentolamine, has been periodically limited in supply in human medicine and is not consistently available for use in veterinary medicine. An alternative protocol proposed for use in people with VE combines topical nitroglycerin application with subcutaneous terbutaline infiltration. In this report, a treatment protocol utilizing these therapies was used to treat 3 dogs with VE and secondary tissue injury., New or Unique Information Provided: This report describes 3 cases of VE-induced tissue injury in dogs. In addition, this report describes the use of perivascular terbutaline infiltration and topical nitroglycerin application as therapeutic management for VE in dogs., (© 2024 The Authors. Journal of Veterinary Emergency and Critical Care published by Wiley Periodicals LLC on behalf of Veterinary Emergency and Critical Care Society.)

Background: An improper host immune response to Mycoplasma pneumoniae generates excessive inflammation, which leads to the impairment of pulmonary ventilation function (PVF). Azithromycin plus inhaled terbutaline has been used in the treatment of Mycoplasma pneumoniae pneumonia (MPP) in children with impaired pulmonary function, but previous randomized controlled trials (RCTs) showed inconsistent efficacy and safety. This study is aimed to firstly provide a systematic review of the combined therapy., Methods: This study was registered at the International Prospective Register of Systematic Reviews (PROSPERO CRD42023452139). A PRISMA-compliant systematic review and meta-analysis was performed. Six English and four Chinese databases were comprehensively searched up to June, 2023. RCTs of azithromycin sequential therapy plus inhaled terbutaline were selected. The revised Cochrane risk of bias tool for randomized trials (RoB2) was used to evaluate the methodological quality of all studies, and meta-analysis was performed using Stata 15.0 with planned subgroup and sensitivity analyses. Publication bias was evaluated by a funnel plot and the Harbord' test. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation recommendations., Results: A total of 1,938 pediatric patients from 20 RCTs were eventually included. The results of meta-analysis showed that combined therapy was able to significantly increase total effectiveness rate (RR = 1.20, 95%CI 1.15 to 1.25), forced expiratory volume in one second (SMD = 1.14, 95%CIs, 0.98 to 1.29), the ratio of forced expiratory volume in one second/forced vital capacity (SMD = 2.16, 95%CIs, 1.46 to 2.86), peak expiratory flow (SMD = 1.17, 95%CIs, 0.91 to 1.43). The combined therapy was associated with a 23% increased risk of adverse reactions compared to azithromycin therapy alone, but no significant differences were found. Harbord regression showed no publication bias (P = 0.148). The overall quality of the evidence ranged from moderate to very low., Conclusions: This first systematic review and meta-analysis suggested that azithromycin sequential therapy plus inhaled terbutaline was safe and beneficial for children with MPP. In addition, the combined therapy represented significant improvement of PVF. Due to lack of high-quality evidence, our results should be confirmed by adequately powered RCTs in the future., (© 2024. The Author(s).)

Background: Myelomeningocele (MMC) is a neural tube defect disease. Antenatal repair of fetal MMC is an alternative to postnatal repair. Many agents can be used as tocolytics during the in utero fetal repair such as β2-agonists and oxytocin receptor antagonists, with possible maternal and fetal repercussions. This study aims to compare maternal arterial blood gas analysis between terbutaline or atosiban, as tocolytic agents, during intrauterine MMC repair., Methods: Retrospective cohort study. Patients were divided into two groups depending on the main tocolytic agent used during intrauterine MMC repair: atosiban (16) or terbutaline (9). Maternal arterial blood gas samples were analyzed on three moments: post induction (baseline, before the start of tocolysis), before extubation, and two hours after the end of the surgery., Results: Twenty-five patients were included and assessed. Before extubation, the terbutaline group showed lower arterial pH (7.347 ± 0.05 vs. 7.396 ± 0.02 for atosiban, p = 0.006) and higher arterial lactate (28.33 ± 12.76 mg.dL -1 vs. 13.06 ± 6.35 mg.dL -1 , for atosiban, p = 0.001) levels., Conclusions: Patients who received terbutaline had more acidosis and higher levels of lactate, compared to those who received atosiban, during intrauterine fetal MMC repair., Competing Interests: Conflicts of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Sociedade Brasileira de Anestesiologia. Published by Elsevier España S.L.U. All rights reserved.)

Quantitative 1 H-NMR became an increasingly important issue in pharmaceutical analytical chemistry. This study used NMR spectroscopy to assay the bronchodilator drug terbutaline sulfate and its pro-drug bambuterol hydrochloride in pure form and pharmaceutical preparations. The technique proceeded using deuterium oxide (D 2 O) as an 1 H-NMR solvent and phloroglucinol anhydrous as an internal standard (IS). Comparatively, to the phloroglucinol signal at 5.9 ppm, the resulting quantitative signals of the studied drugs were corrected. The terbutaline singlet signal at 6.3 ppm was chosen for quantification, while the bambuterol quantitative singlet signal was at 2.9 ppm. The two drugs were rectilinear over the concentration range of 1.0-16.0 mg/mL. LOD values were 0.19 and 0.21 mg/mL while LOQ values were 0.58 and 0.64 mg/mL for terbutaline and bambuterol respectively. The developed method has been validated according to the International Conference of Harmonization (ICH) regarding linearity, accuracy, precision, specificity, and robustness. A greenness profile assessment was applied, and the method proved to be green. The method enables the assay of the two drugs in pure drug and pharmaceutical preparations. The method also enables the assay of the two drugs in the presence of each other; thus, it is considered a stability-indicating method where terbutaline is an acid degradation product of bambuterol., (© 2024. The Author(s).)

Physicochemical properties (drug release, peel strength, adhesion, and stiffness) of Hokunalin ® Tape (Hokunalin) and 13 generic transdermal bronchodilator patches containing tulobuterol were characterized and evaluated for comparison. Drug-release studies evaluating sustained release behavior demonstrated better performance by the drug Hokunalin, than the generics MED, YP, Sawai, and Teikoku. Hokunalin yield a 16.2% release 1 hour after initiation, 30.1% at 3 hours, 50.0% at 8 hours. In comparison, the generics MED, YP, Sawai, and Teikoku showed an intermediate release behavior to that of Hokunalin, with more than 80% release after 8 hours. A 90-degree peel adhesion test for tape peel strength demonstrated that the generic MED (4.99 N), YP (3.26 N), Sawai (4.17 N), and Teikoku (4.37 N) tapes yielded significantly higher values compared to Hokunalin (2.66 N). Probe tack tests, evaluating adhesive strength, yielded significantly higher values for the generics HMT (4.89 N)and Towa (4.25 N) compared to Hokunalin (3.66 N). Furthermore, for the stiffness-softness test, a significantly higher value was obtained for each generic yielded compared to Hokunalin (3.7-degree). These factors are important components of product qualities that affect treatment efficacy, including "ease of application" and other usability factors.

Objectives: Children with status asthmaticus refractory to first-line therapies of systemic corticosteroids and inhaled beta-agonists often receive additional treatments. Because there are no national guidelines on the use of asthma therapies in the PICU, we sought to evaluate institutional variability in the use of adjunctive asthma treatments and associations with length of stay (LOS) and PICU use., Design: Multicenter retrospective cohort study., Setting: Administrative data from the Pediatric Health Information Systems (PHIS) database., Patients: All inpatients 2-18 years old were admitted to a PHIS hospital between 2013 and 2021 with a diagnostic code for asthma., Interventions: None., Measurements and Main Results: This study included 213,506 inpatient encounters for asthma, of which 29,026 patient encounters included care in a PICU from 39 institutions. Among these PICU encounters, large variability was seen across institutions in both the number of adjunctive asthma therapies used per encounter (min: 0.6, median: 1.7, max: 2.5, p < 0.01) and types of adjunctive asthma therapies (aminophylline, ipratropium, magnesium, epinephrine, and terbutaline) used. The center-level median hospital LOS ranged from 1 (interquartile range [IQR]: 1, 3) to 4 (3, 6) days. Among all the 213,506 inpatient encounters for asthma, the range of asthma admissions that resulted in PICU admission varied between centers from 5.2% to 47.3%. The average number of adjunctive therapies used per institution was not significantly associated with hospital LOS ( p = 0.81) nor the percentage of encounters with PICU admission ( p = 0.47)., Conclusions: Use of adjunctive therapies for status asthmaticus varies widely among large children's hospitals and was not associated with hospital LOS or the percentage of encounters with PICU admission. Wide variance presents an opportunity for standardizing care with evidence-based guidelines to optimize outcomes and decrease adverse treatment effects and hospital costs., Competing Interests: Dr. Shein received funding from Ceribell and Hill Ward Henderson. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)

Objective: To assess the therapeutic efficacy of acupuncture in combination with Chinese herbs for treatment of horses affected with anhidrosis., Animals: 44 horses affected with anhidrosis for up to 3 years' duration were enrolled. Inclusion required both compatible clinical signs and results of a quantitative intradermal terbutaline sweat test., Methods: Study horses were randomly allocated into 2 groups. Group 1 (n = 19) was treated with daily Chinese herbs and 4 weekly acupuncture sessions. Group 2 (n = 25) was given daily hay powder as a placebo and 4 weekly sham acupuncture sessions. Horses were tested by quantitative intradermal terbutaline sweat test within 2 days after treatment completion and again 4 weeks following treatment., Results: Terbutaline-induced sweat responses (mg) were not different between groups within 2 days and 4 weeks after treatment. Two days after treatment, ratios of sweat responses (compared to baseline) were higher (P < .05) in the treatment group compared to the placebo group at terbutaline concentrations of 1.0, 100, and 1,000 µg/mL. The number of horses responding to treatment was higher in the treatment group (5/19 [26%]), compared to horses in the placebo group (1/25 [4%]) for 1 of 5 terbutaline concentrations 2 days (10 µg/mL) or 4 weeks (0.1 µg/mL) after treatment., Clinical Relevance: Ratios of sweat responses were higher in treatment horses 2 days after treatment, compared to baseline, but not 4 weeks later. The efficacy of a traditional Chinese veterinary medicine protocol for anhidrosis treatment with acupuncture and Chinese herbs was low but higher in treated horses compared with placebo.

Background: T helper 17 (Th17) cells produce IL-17A cytokine and can exacerbate autoimmune diseases and asthma. The β2 adrenergic receptor is a g protein-coupled receptor that induces cAMP second messenger pathways. We tested the hypothesis that terbutaline, a β2-adrenergic receptor-specific agonist, promotes IL-17 secretion by memory Th17 cells in a cAMP and PKA-dependent manner., Methods: Venous peripheral blood mononuclear cells (PBMC) from healthy human participants were activated with anti-CD3 and anti-CD28 antibodies. Secreted IL-17A was measured by enzyme linked immunosorbent assay, intracellular IL-17A, and RORγ were measured using flow cytometry, and RORC by qPCR. Memory CD3 + CD4 + CD45RA - CD45RO + T cells were obtained by immunomagnetic negative selection and activated with tri-antibody complex CD3/CD28/CD2. Secreted IL-17A, intracellular IL-17A, RORC were measured, and phosphorylated-serine133-CREB was measured by western blotting memory Th cells., Results: Terbutaline increased IL-17A (p < 0.001), IL-17A + cells (p < 0.05), and RORC in activated PBMC and memory Th cells. The PKA inhibitors H89 (p < 0.001) and Rp-cAMP (p < 0.01) abrogated the effects of terbutaline on IL-17A secretion in PBMC and memory T cells. Rolipram increased IL-17A (p < 0.01) to a similar extent as terbutaline. P-Ser133-CREB was increased by terbutaline (p < 0.05) in memory T cells., Conclusion: Terbutaline augments memory Th17 cells in lymphocytes from healthy participants. This could exacerbate autoimmune diseases or asthma, in cases where Th17 cells are considered to be pro-inflammatory., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Peripheral administration of norepinephrine is restricted due to the association of extravasation with tissue necrosis., Method: Scoping review with the objective of describing the adverse effects related to the administration of norepinephrine through short peripheral venous access and the characteristics of drug administration in patients hospitalized in ICU, surgery, and emergency services., Results: 12 studies with heterogeneous characteristics by size and type of population were included. The proportion of complications associated with peripheral norepinephrine administration was less than 12% in observational studies and it was less than 2% in those that used doses less than 0.13μg/kg/min, and concentrations less than 22.3μg/mL. The main associated complication was extravasation and there were no cases of tissue necrosis at the venipuncture site, some extravasation cases were treated with phentolamine, terbutaline or topical nitroglycerin. The drug administration time ranged between 1 and 528hours with a weighted mean of 2.78h., Conclusion: The main adverse effect was extravasation, no additional complications occurred, phentolamine and terbutaline seem to be useful, and its availability is a necessity. It is essential for the nursing staff to carry out a close assessment and comprehensive care in patients receiving norepinephrine by peripheral route., (Copyright © 2022 The Author(s). Published by Elsevier España, S.L.U. All rights reserved.)

Silver nanoparticles (AgNPs) were found to significantly quench the fluorescence of bambuterol hydrochloride (BAM) and its active metabolite terbutaline sulfate (TER). The intrinsic fluorescence intensity of each of BAM (at 264/292 nm) and TER (at 276/306 nm) decreased by the gradual addition of AgNPs. Quenching of the steady state fluorescence of BAM and TER probably resulted from the energy transfer to the photo-excited state of AgNPs. The estimated Stern-Volmer quenching constant at several temperature settings proved that the quenching mechanism of the two drugs was dynamic quenching in case of BAM while it was static quenching in case of TER. The number of binding sites, binding constants, and corresponding thermodynamic parameters depending on the interaction system were estimated at 293, 313, and 333 °K and the results obtained were interpreted., (© 2023. The Author(s).)

Systemic capillary leak syndrome is a rare derangement of endothelial function characterised by extravasation of plasma and proteins into the interstitial space. Primary capillary leak syndrome is a rare, episodic medical illness of unknown molecular pathology while secondary capillary leak syndrome may be precipitated by any number of inflammatory and infectious syndromes. Decompression sickness, a disorder of depressurisation, has been identified as a very rare trigger. We present a structured case report of systemic capillary leak syndrome secondary to decompression sickness following deep diving, informing physicians of this potential complication. No pharmacological therapy has substantial evidence in the treatment of acute systemic capillary leak syndrome. By review of current recommendations for acute management, we also emphasise an observed positive response to judicious fluid resuscitation and an oral cyclic AMP-elevating agent (ie, terbutaline)., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

A Japanese man experienced three episodes of hypovolemic shock and was diagnosed with systemic capillary leak syndrome (SCLS). He developed SCLS exacerbation 2 days after receiving a second dose of the Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine, 1 year after the third episode. After fluid therapy and albumin administration, we initiated terbutaline and theophylline prophylaxis for SCLS. A literature review revealed that SCLS attacks often occur 1-2 days after the second COVID-19 vaccination. Patients with a history of SCLS should avoid COVID-19 vaccination and be carefully monitored for 1-2 days if they receive the vaccine.

Four clinically healthy red wolves ( Canis rufus ) developed hyperkalemia during routine anesthetic procedures. All cases were anesthetized using a combination of dexmedetomidine (10-24 mcg/kg), ketamine (2-3 mg/kg), and either midazolam (0.25-0.5 mg/kg) or butorphanol (0.2-0.48 mg/kg). Additional anesthetics were given to effect. Total anesthetic time ranged from 60 to 420 min. Three out of four cases were treated using terbutaline (0.01 mg/kg SC), which successfully resolved the hyperkalemia. No bradyarrhythmias were seen in any cases where electrocardiography (ECG) was monitored (3/4). All cases recovered from anesthesia, with one prolonged recovery. All animals are clinically healthy at the time of writing. Factors including anesthetic duration, the use of α-2 agonists, hyperthermia, and genetics are discussed as possible triggers for hyperkalemia. Serial blood gases, with electrolyte measurements, are recommended during anesthesia of red wolves, particularly when anesthetic time may be prolonged or the patient suffers from hyperthermia. Terbutaline appears to be a successful treatment should hyperkalemia arise.

An analytical method combining high-throughput automatic solid-phase extraction with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed to determine 16 antibiotics (macrolides, tetracyclines, quinolones, and sulfonamides) and 4 β -agonists (terbutaline, salbutamol, ractopamine, and clenbuterol) in human urine samples. After thawing at room temperature, 1 mL of urine was sampled and the internal standard was added, followed by the addition of 200 μL ammonium acetate buffer and 20 μL β -glucuronidase, and the mixture was incubated at 37 ℃ overnight. Automatic solid-phase extraction was used to extract the target compounds from the urine samples, and the recoveries were compared using different solid-phase extraction 96-well plates (PRiME MCX, Sep-Pak C 18 , PRiME HLB), types and volumes of rinse solutions and eluents. Satisfactory recoveries of the 20 target compounds were obtained using the Oasis PRiME HLB 96-well plate, with 1.5 mL 10% (v/v) methanol aqueous solution and 2.0 mL methanol as the rinse solution and eluent, respectively. The eluent was concentrated under nitrogen gas at 45 ℃, and the recoveries of the target compounds were compared under different conditions (completely or almost dry, drying to 1 mL, and adding water as a protective agent), and the recovery rate was optimal when water was added as a protective agent. In this study, two types of analytical columns (ACQUITY BEH C 18 and ACQUITY HSS T 3 ) and different gradient elution procedures and mobile phases were compared. The optimal chromatographic effect was realized using an HSS T 3 column (100 mm×3.0 mm, 1.8 μm) and 0.1% (v/v) formic acid aqueous solution-0.1% (v/v) formic acid in acetonitrile as the mobile phase in gradient elution at a flow rate of 0.3 mL/min. Comparing the peaks observed using different proportions of methanol aqueous solution and the initial mobile phase as the injection solvent revealed that 30% (v/v) methanol aqueous solution was the optimal solution in terms of peak shape and signal-to-noise ratio. MS was conducted using positive electrospray ionization (ESI + ) in multiple reaction monitoring (MRM) mode, and the MS parameters were optimized, including the curtain (CUR) and collision gases (CAD). The standard curve obtained using this method exhibited a good linearity (correlation coefficient>0.997), and the respective limits of detection and quantification were 0.02-0.12 ng/mL and 0.06-0.41 ng/mL. At spiked levels of 0.25, 2.5, and 12.5 ng/mL, the recoveries were in the range of 81.7%-120.0% (except that of tetracycline), the intra- and inter-day RSDs ( n =6) were 1.1%-11.0% and 1.2%-13.0%, respectively. Azithromycin, trimethoprim, terbutaline, salbutamol, ractopamine, and clenbuterol displayed moderate matrix effects, but all targets exhibited weak matrix effects after correction using the isotope internal standard. To evaluate the accuracy of this method, BCR-503 (containing salbutamol and clenbuterol) and internal quality control samples were used and the concentrations of salbutamol and clenbuterol were within the reference ranges. Additionally, the mean concentrations of the 20 target compounds of two different internal quality control samples after 7 measurements were in the ranges of 0.44-0.59 ng/mL (0.5 ng/mL) and 1.72-2.16 ng/mL (2.0 ng/mL), respectively, which were satisfactory. In this study, the analytical method employed automatic sample pretreatment with a 96-well solid-phase extraction plate, and the detection efficiency was considerably improved. This method displays the advantages of simple operation, ideal recovery, a high sensitivity and weak matrix effect, which satisfies the requirements for the simultaneous determination of 16 antibiotics and 4 β -agonists in human urine samples. This study provides a crucial method for use in monitoring antibiotics and β -agonists in human urine and studying their exposure characteristics and health risks.

Extravasation is the leakage of intravenous solutions into surrounding tissues, which can be influenced by drug properties, infusion techniques, and patient-related risk factors. Although peripheral administration of vesicants may increase the risk of extravasation injuries, the time and resources required for central venous catheter placement may delay administration of time-sensitive therapies. Recent literature gathered from the growing use of peripheral vasopressors and hypertonic sodium suggests low risk of harm for initiating these emergent therapies peripherally, which may prevent delays and improve patient outcomes. Physiochemical causes of tissue injury include vasoconstriction, pH-mediated, osmolar-mediated, and cytotoxic mechanisms of extravasation injuries. Acidic agents, such as promethazine, amiodarone, and vancomycin, may cause edema, sloughing, and necrosis secondary to cellular desiccation. Alternatively, basic agents, such as phenytoin and acyclovir, may be more caustic due to deeper tissue penetration of the dissociated hydroxide ions. Osmotically active agents cause cellular damage as a result of osmotic shifts across cellular membranes in addition to agent-specific toxicities, such as calcium-induced vasoconstriction and calcifications or arginine-induced leakage of potassium causing apoptosis. A new category has been proposed to identify absorption-refractory mechanisms of injury in which agents such as propofol and lipids may persist in the extravasated space and cause necrosis or compartment syndrome. Pharmacological antidotes may be useful in select extravasations but requires prompt recognition and frequently complex administration strategies. Historically, intradermal phentolamine has been the preferred agent for vasopressor extravasations, but frequent supply shortages have led to the emergence of terbutaline, a β 2 -agonist, as an acceptable alternative treatment option. For hyperosmolar and pH-related mechanisms of injuries, hyaluronidase is most commonly used to facilitate absorption and dispersion of injected agents. However, extravasation management is largely supportive and requires a protocolized multidisciplinary approach for early detection, treatment, and timely surgical referral when required to minimize adverse events., (© 2023 Pharmacotherapy Publications, Inc.)

Background: Recent research in our laboratory shows that CD4+ T cells express the β2 adrenergic receptor (β2-AR), and the sympathetic neurotransmitter norepinephrine regulates the function of T cells via β2-AR signaling. However, the immunoregulatory effect of β2-AR and its related mechanisms on rheumatoid arthritis is unknown., Objective: To explore the effects of β2-AR in collagen-induced arthritis (CIA) on the imbalance of T helper (Th) 17/ regulatory T (Treg) cells., Methods: In DBA1/J mice, collagen type II was injected intradermally at the tail base to prepare the CIA model. The specific β2-AR agonist, terbutaline (TBL), was administered intraperitoneally beginning on day 31 and continuing until day 47 after primary vaccination, twice a day. Magnetic beads were used to sort CD3+ T cells subsets from spleen tissues., Results: In vivo, β2-AR agonist TBL alleviated arthritis symptoms in the CIA mice including histopathology of the ankle joints, four limbs' arthritis score, the thickness of ankle joints, and rear paws. After TBL treatment, in the ankle joints, the levels of proinflammatory factors (IL-17/22) notably decreased and the levels of immunosuppressive factors (IL-10/TGF-β) significantly increased. In vitro, ROR-γt protein expression, Th17 cell number, mRNA expression and the releasing of IL-17/22 from CD3+ T cells reduced following TBL administration. Moreover, TBL enhanced the anti-inflammatory responses of Treg cells., Conclusion: These results suggest that β2-AR activation exerts anti-inflammatory effects through the amelioration of Th17/Treg imbalance in the CIA disease.

Terbutaline is used for the management of bronchospasm associated with asthma, bronchitis, emphysema, and chronic obstructive pulmonary disease. A systematic review would be beneficial to assess the impact of routes of administration, stereoisomerism, disease states, smoking, age, exercise, and chronobiology on pharmacokinetics (PK) of terbutaline in humans. PubMed and Google Scholar databases were searched to screen all the relevant articles consisting of at least one of the PK parameters after administration of oral, inhaled, and intravenous (IV) terbutaline in humans. Oral studies of terbutaline depicted a linear relationship between plasma concentration (C p ) and the administered dose. The IV studies demonstrated multi-exponential behavior for disposition and renal clearance. Higher systemic availability was observed with inhaled as compared to oral route, and chrono-pharmacokinetic behavior was notable. Time to reach maximum plasma concentration (T max ) was prolonged, and maximum plasma concentration (C max ) was lowered after exercise. The primary route of excretion in chronic kidney disease (CKD) patients is reported to be nonrenal. In pregnant women, the C p of terbutaline is lowered and clearance is increased. The addition of theophylline to terbutaline did not affect the PK of terbutaline; hence, both can be used without dose adjustment. This review summarizes all the available PK parameters of terbutaline, and it may be helpful for researchers in the development and evaluation of PK models as well as in designing optimal dosage regimens in different clinical conditions., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Several technical features influencing bronchodilator delivery were evaluated using different vaping drug delivery systems (VDDS)., Methods: Terbutaline in powder form, combined with 1, 3- propanediol used as e-liquid was tested at different concentrations (1 and 2.5 mg/mL), power levels (15 W and 30 W), and set applied resistances (0.15 to 1.5 O) to compare the efficiency of three VDDS (GS AIR2, GS TANK, CUBIS). Samples were collected with a Glass Twin Impinger (GTI). A High Performance Liquid Chromatography (HPLC) was used for drug quantification. The Next Generation Impactor (NGI) measured particle size distribution. Results were also considered with a clinical jet nebulizer (Cirrus TM 2, 2 mL of terbutaline at 2.5 mg/mL)., Results: GS AIR2 with resistance = 1.5 O; power = 15 W, and [Terbutaline] = 2.5 mg/mL represents the optimal VDDS conditions to deliver a respirable dose of 20.05 ± 4.2 µg/puff with a mass median aerodynamic diameter (MMAD) of 1.41 ± 0.03 µm. Thus, 52 puffs were required (lasting approximately 15 min of vaping) to reach similar respirable dose and MMAD compared to nebulization., Conclusion: We proved that several crucial VDDS technical parameters govern the performance of respiratory bronchodilator delivery including the resistance, power level and atomizer design., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: Current treatments for blast-induced lung injury are limited to supportive procedures including mechanical ventilation. The study aimed to investigate the role of post-trauma-induced oedema generation in the function of time and trauma intensity and the probable role of beta 2-adrenergic receptors (β2-ARs) agonists on pulmonary oedema. The study is conducted using an ex vivo model after an experimental in vivo blast-induced thorax trauma in rats. Methods: Rats were randomised and divided into two groups, blast and sham. The blast group were anaesthetised and exposed to the blast wave (3.16 ± 0.43 bar) at a distance of 3.5 cm from the thorax level. The rats were sacrificed 10 min after the blast, the lungs explanted and treated with terbutaline, formoterol, propranolol or amiloride to assess the involvement of sodium transport. Other groups of rats were exposed to distances of 5 and 7 cm from the thorax to reduce the intensity of the injury. Further, one group of rats was studied after 180 min and one after 360 min after a 3.5 cm blast injury. Sham controls were exposed to identical procedures except for receiving blast overpressure. Results: Lung injury and oedema generation depended on time after injury and injury intensity. Perfusion with amiloride resulted in a further increase in oedema formation as indicated by weight gain (p < 0.001), diminished tidal volume (Tv) (p < 0.001), and increased airway resistance (p < 0.001). Formoterol caused a significant increase in the Tv (p < 0.001) and a significant decrease in the airway resistance (p < 0.01), while the lung weight was not influenced. Trauma-related oedema was significantly reduced by terbutaline in terms of lung weight gain (p < 0.01), Tv (p < 0.001), and airway resistance (p < 0.01) compared to control blast-injured lungs. Terbutaline-induced effects were completely blocked by the β-receptor antagonist propranolol (p < 0.05). Similarly, amiloride, which was added to terbutaline perfusion, reversed terbutaline-induced weight gain reduction (p < 0.05). Conclusions: β2-adrenoceptor stimulation had a beneficial impact by amiloride-dependent sodium and therefore, fluid transport mechanisms on the short-term ex vivo oedema generation in a trauma-induced in vivo lung injury of rats.

Objective: This study aimed to evaluate the effectiveness of intrapartum acute tocolysis for nonreassuring fetal heart rate tracing in decreasing the incidence of cesarean delivery. Secondary outcomes included modes of delivery other than cesarean delivery, successful acute tocolysis, time-to-delivery interval, and short-term perinatal outcomes., Data Sources: Searches were performed in MEDLINE/PubMed, Embase, Scopus, the Cochrane Central Register of Controlled Trials and Reviews, ClinicalTrials.gov, and the International Clinical Trials Registry Platform from the inception of each database until February 2022., Study Eligibility Criteria: Selection criteria included randomized controlled trials of laboring patients with singleton gestations randomized to receive intrapartum acute tocolysis for nonreassuring fetal heart rate tracing, as defined by the original trial., Methods: All analyses were done using an intention-to-treat approach, evaluating women according to the treatment group to which they were randomly allocated in the original trials. A frequentist network-meta-analysis was performed., Results: Four randomized clinical trials were eligible, including 605 patients with nonreassuring fetal heart rate tracing and singleton gestations at gestational ages >32 weeks. The cesarean delivery rate was similar among patients managed with different types of acute tocolysis. Acute tocolysis, compared with emergency delivery, was associated with improved neonatal acid-base status (notably decreasing the prevalence of base deficit >12 mmol/L [beta-2 agonists odds ratio, 0.61; 95% confidence interval, 0.37-0.99] and the rate of neonatal intensive care unit admission [beta-2 agonists odds ratio, 0.42; 95% confidence interval, 0.22-0.78]) and with an increase in the time-to-delivery interval (beta-2 agonists mean difference, 17.62 minutes; 95% confidence interval, 15.66-19.58); there was no reduction of cesarean delivery rate, showing an increased rate with atosiban and beta-2 agonists., Conclusion: The cesarean delivery rate was not reduced by acute tocolysis when used for nonreassuring fetal heart rate tracing during labor. Acute tocolysis is associated with improved short-term fetal outcomes and safely increases the time-to-delivery interval., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Terbutaline is mainly metabolized by sulfoconjugation stereoselectively, favoring its (S)-(+) enantiomer. Reported chiral separations of Terbutaline enantiomers were achieved by various chromatographic methods. However, the simultaneous enantioseparation of Terbutaline and the monosulfate conjugate metabolites was never reported. This study aims at shedding light on the influential factors and interactions leading to successful enantioseparation of Terbutaline and its monosulfate conjugate pairs by Supercritical Fluid Chromatography (SFC) for the first time within a Quality by Design framework using Design of Experiments. The effect of molarity of mobile phase additive, mobile phase flow rate, column temperature and back pressure were evaluated. Compared to previous reports, the response surface interestingly revealed the favorability of high temperature and high flow rate up to 2.25 ml/min for resolution of the two pairs of enantiomers on polysaccharide chiral stationary phase CHIRALPAK IC. In addition, a switch in the elution order of Terbutaline and the sulfate conjugate peak pairs was observed upon elimination of the mobile phase additive where the sulfate conjugate underwent intra-molecular ionic interactions and the change in elution order was only due to TER behavior. The multifactorial interactions would not have been detected with the common one-factor-at-a-time approach during method development, demonstrating the superiority and importance of the Analytical Quality by Design frame in enantioseparation., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Chiral covalent organic frameworks (CCOFs) have recently exhibited particularly promising potential as effective chiral stationary phases (CSPs) for open tubular capillary electrochromatography (OT-CEC) enantioseparation. However, it remains difficult to synthesis of CCOFs and preparation of CCOFs coated capillary under mild reaction conditions. In this work, we designed and fabricated a CCOF (CB-DA-COF) with high chemical stability and high specific surface area at room temperature. Then, through one-step in situ growth method, the chiral CB-DA-COF coated capillary was fabricated at room temperature for the first time. This method requires neither pre-modification to the capillary by organic molecular building units nor harsh reaction conditions, and the preparation time of the CCOF coating was significantly shortened (within 2 h). This chiral CB-DA-COF coated capillary showed excellent enantioseparation ability and stability. Under optimal conditions, rapid enantioseparation (within 5 min) could be achieved for six enantiomers including terbutaline, propranolol, phenylephrine, verapamil, norepinephrine and isoprenaline. And, no significant change was observed in enantioseparation efficiency after over 200 runs. The relative standard deviations (RSDs) of the analyte's migration time for intra-day, inter-day and column-to-column were within the range of 0.8-3.5% (n = 5), 1.5-4.7% (n = 3) and 4.3-8.3% (n = 3), respectively. In addition, the enantioseparation mechanism was studied, which indicated that binding energy between of enantiomers and chiral site were the main factors for enantioseparation., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest or personal relationships that could have appeared to influence the work reported here., (Copyright © 2022. Published by Elsevier B.V.)

Acute lung injury (ALI), characterized by an acute onset of severe hypoxemia, is a common and devastating syndrome usually triggered by lipopolysaccharide (LPS) infection from bacteria. This study is intended to explore whether terbutaline can alleviate LPS-induced human pulmonary microvascular endothelial cell (HPMVEC) injury through cAMP/Epac signaling. LPS was utilized to induce ALI in HPMVECs, and after exposure of LPS-induced HPMVECs to terbutaline, the cellular functions including cell viability and apoptosis were measured by cell counting kit-8 and terminal deoxynucleotidyl transferase dUTP nick-end labeling. The protein expression related to cAMP/Epac signaling, apoptosis, and that of tight junction and inflammatory factors were evaluated at the same time. The effects of terbutaline on cellular functions were confirmed again after the addition of antagonists of cAMP and Epac, respectively. The levels of both cAMP and Epac reduced by LPS was concentration-dependently increased by terbutaline. The apoptosis and endothelial cell permeability damage of LPS-induced HPMVECs were enhanced after the addition of KT-5720 and ESI-09. The beneficial effects of terbutaline on alleviating the inflammation and apoptosis in HPMVECs injured by LPS are mediated by cAMP/Epac signaling, and this evidence would demonstrate the potential of terbutaline in the treatment of ALI., (© 2021 Wiley Periodicals LLC.)

Myasthenia gravis (MG) is the most extensively studied antibody-mediated disease in humans. Substantial progress has been made in the treatment of MG in the last century, resulting in a change of its natural course from a disease with poor prognosis with a high mortality rate in the early 20th century to a treatable condition with a large proportion of patients attaining very good disease control. This review summarizes the current treatment options for MG, including non-immunosuppressive and immunosuppressive treatments, as well as thymectomy and targeted immunomodulatory drugs.

The aim of this study is to develop a portable wireless intelligent nanosensor (PWIN) for rapid cost-effective on-site determination of terbutaline (TRA) residue in meat products outdoors in comparison with traditional nanosensor and high-performance liquid chromatography (HPLC). The layer-by-layer sandwiched nanohybrid fabricated by platinum-palladium nanoparticles, carboxylated graphene and graphene-like molybdenum disulfide displayed a wide linear range of 0.55-14.9 μmol/L using the portable potentiostat with smartphone, and the result was almost close to the linear range (0.4-14 μmol/L) using the traditional potentiostat with desktop computer for TRA. The limit of detections were identified as 0.44 μmol/L and 0.18 μmol/L, respectively. PWIN displayed satisfactory recovery (91%-98.43%) of TRA in samples by the standard addition method and in comparison with both traditional sensor (93.79%-98%) and HPLC (93.4%-98.6%), revealing that PWIN for rapid cost-effective on-site analysis in the food safety field is feasible., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: The performance of new-generation high-power electronic nicotine delivery system (ENDS) for the administration of inhaled terbutaline was assessed., Methods: The formulation of e-liquid was carried out using terbutaline in combination with 1, 3- propanediol. Several terbutaline concentrations (from 0.3125 to 2.500 mg / mL) and power levels (from 15 to 35 W) were assessed using a box type ENDS. The respirable drug dose was determined using a Glass Twin Impinger and quantified by liquid chromatography coupled with a UV-detector. The Next Generation Impactor and the Dekati Low Pressure Impactor were used to measure the aerosol particle size distribution in drug mass. The results were compared with a jet nebulizer (Cirrus TM 2) similar to the usual clinical conditions (2 mL at [terbutaline] of 2.5 mg / mL)., Results: The optimal conditions to maximize terbutaline delivery using ENDS are a drug concentration at 1 mg/mL, and a power level at 30 W, to reach a respirable dose of 8.73 ± 0.90 µg/puff. By contrast, during a 5 min nebulization, the respirable dose of terbutaline was 1040 ± 33 µg whatever the cascade impactors and the aerosol devices used. The mass median aerodynamic diameter (MMAD) remains similar for jet nebulizer and ENDS in the 1.74-2.07 µm range., Conclusion: Compared to the jet nebulizer, a same respirable dose of terbutaline at the same range of aerosol size distribution was delivered by ENDS if 120 puffs were performed. The ENDS can be considered as an alternative aerosol device for terbutaline delivery., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

For the first time it is demonstrated that zeolitic imidazolate framework-8 electrospun nanofibers (ZIF-8 NF) could serve as electrochemiluminescence (ECL) accelerator for the facile detection of terbutaline residual. A novel ECL sensor for the determination of terbutaline was fabricated based on ZIF-8 NF. The ZIF-8 NF were successfully prepared according to electrospinning and in-situ growth method. First, chitosan was modified on the surface of the electrode, and then the ZIF-8 NF was modified onto the upper layer of the chitosan. Taking advantages of chitosan and ZIF-8 NF in conductivity and electrocatalysis, the modified electrode presents obvious ECL phenomenon in 0.2 M PBS solution (pH 10.0) containing 0.025 M luminol. After the addition of terbutaline, ECL intensity decreased significantly, and the decreasing value showed a linear relationship with the logarithm of terbutaline concentration. The linear range was from 2.0 × 10 -10 to 2.0 × 10 -5  M, and the detection limit was 1.41 × 10 -11  M (3σ/m). The method had high sensitivity, good stability, and good applicability to actual pork samples., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

In this research, reduced graphene oxide (RGO) which is a form of graphene oxide (GO) was formed through a reduction process using a "green agent" called Ascorbic acid (AA). RGO was then modified on the surface of the glassy carbon electrode (GCE) to generate RGO/GCE (an advanced electrode). The RGO/GCE was then used to detect Terbutaline (TB) in urine samples of volunteer athletes (n = 5) using well-known spectrophotometric analyses including X-ray diffraction analysis (XRD), Fourier-transform infrared spectroscopy (FT-IR), ultraviolet-visible Spectroscopy (UV-Vis), and Raman and electrochemical methods using voltammetric analyses such as differential pulse anodic stripping voltammetry (DP-ASV) and cyclic voltammetry (CV). Comparing various analysis methods using RGO/GCE to detect TB in human urine samples, voltammetric analysis specifically DP-ASV demonstrated higher sensitivity and selectivity in detecting TB than spectrophotometric analyses. Thus, in this study, several factors that would affect the voltammetric signals such as pH and interferents were evaluated and the electroactive surface area was also calculated. Our findings indicated that the RGO/GCE showed excellent repeatability, reproducibility, and long-term stability suggesting that TB could be detected more effectively using RGO/GCE than bare GCE. The detection limit of 0.0052 μM achieved in this study indicated that RGO/GCE can effectively detect TB in human urine while demonstrating reasonable selectivity and sensitivity., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The long-term use of adrenergic medication in treating various conditions, such as asthma, increases the chances of bone fracture. Dynamic mechanical loading at a specific time is a method for improving bone quality and promoting healing. Therefore, we hypothesized that precisely controlling the mechanical environment can contribute to the alleviation of the negative effects of chronic treatment with the common asthma drug terbutaline, which is a β2-adrenergic receptor agonist that facilitates bone homeostasis and defect repair through its anabolic effect on osteogenic cells. Our in vitro results showed that terbutaline can directly inhibit osteogenesis by impairing osteogenic differentiation and mineralization. Chronic treatment in vivo was simulated by administering terbutaline to C57BL/6J mice for 4 weeks before bone defect surgery and mechanical loading. We utilized a stabilized tibial defect model, which allowed the application of anabolic mechanical loading. During homeostasis, chronic terbutaline treatment reduced the bone formation rate, the fracture toughness of long bones, and the concentrations of bone formation markers in the sera. During defect repair, terbutaline decreased the bone volume, type H vessel, and total blood vessel volume. Terbutaline treatment reduced the number of osteogenic cells. Periostin, which was secreted mainly by Prrx1+ osteoprogenitors and F4/80+ macrophages, was inhibited by treating the bone defect with terbutaline. Interestingly, controlled mechanical loading facilitated the recovery of bone volume and periostin expression and the number of osteogenic cells within the defect. In conclusion, mechanical loading can rescue negative effects on new bone accrual and repair induced by chronic terbutaline treatment., (© 2021 Federation of American Societies for Experimental Biology.)

Objective: Hypersympathetic activity is prominent in rheumatoid arthritis, and major life stressors precede onset in ~80% of patients. These findings and others support a link between stress, the sympathetic nervous system and disease onset and progression. Here, we extend previous research by evaluating how selective peripherally acting α/β 2 -adrenergic drugs affect joint destruction in adjuvant-induced arthritis., Methods: Complete Freund's adjuvant induced inflammatory arthritis in male Lewis rats. Controls received no treatment. Arthritic rats then received vehicle or twice-daily treatment with the α-adrenergic antagonist, phentolamine (0.5 mg/day) and the β 2 -adrenergic agonist, terbutaline (1200 µg/day, collectively named SH1293) from day (D) of disease onset (D12) through acute (D21) and severe disease (D28). Disease progression was assessed in the hind limbs using dorsoplantar widths, X-ray analysis, micro-computed tomography, and routine histology on D14, D21, and D28 post-immunization., Results: On D21, SH1293 significantly attenuated arthritis in the hind limbs, based on reduced lymphocytic infiltration, preservation of cartilage, and bone volume. Pannus formation and sympathetic nerve loss were not affected by SH1293. Bone area and osteoclast number revealed high- and low-treatment-responding groups. In high-responding rats, treatment with SH1293 significantly preserved bone area and decreased osteoclast number, data that correlated with drug-mediated joint preservation. SH1293 suppressed abnormal bone formation based on reduced production of osteophytes. On D28, the arthritic sparing effects of SH1293 on lymphocytic infiltration, cartilage and bone sparing were maintained at the expense of bone marrow adipocity. However, sympathetic nerves were retracted from the talocrural joint., Conclusion and Significance: Our findings support a significant delay in early arthritis progression by treatment with SH1293. Targeting sympathetic neurotransmission may provide a strategy to slow disease progression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bellinger, Wood, Wergedal and Lorton.)

Objectives: This study focused on patients with chronic obstructive pulmonary disease (COPD) and aimed at investigating the effect of terbutaline plus doxofylline on their pulmonary function and quality of life., Methods: Ninety COPD patients were divided by using a random number table into a control group (administration of doxofylline) and experimental group (administration of terbutaline combined with doxofylline), with 45 patients in each group. The therapeutic efficacy, pre- and post-treatment pulmonary function and the quality of life were compared between the control and experimental groups., Results: After treatment, patients in the experimental group had lower levels of interleukin-8, tumor necrosis factor α and C-reactive protein (all P<0.001), higher forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEVl/FVC (all P<0.001), and lower total score of COPD assessment test (P<0.05) compared with the control group., Conclusion: Terbutaline combined with doxofylline for the treatment of COPD patients can efficiently decrease inflammatory factor levels, and bring them better pulmonary function and quality of life., Competing Interests: None., (AJTR Copyright © 2021.)

Background: To investigate the efficacy of glucocorticoid and terbutaline in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD)., Methods: 248 patients with AECOPD were assigned into two groups, 124 patients in the control group were only given terbutaline treatment, while 124 patients in the experimental group were treated with glucocorticoid and terbutaline. The effect on lung function and blood gas indexes were compared between the two groups., Results: The total effective rate of the treatment with glucocorticoid and terbutaline was higher than that of control group (P < 0.05). After treatment, the pulmonary function indexes such as FEV 1 , FVC and PaO 2 levels in the two groups were significantly higher than those before treatment, PaCO 2 levels were significantly lower than that before the treatment (P < 0.05)., Conclusions: The combined use of glucocorticoid and terbutaline could effectively improve the lung function and blood gas indexes. It's of great significance to promote the rehabilitation of patients with AECOPD, and it provides insights for future clinical practice., Competing Interests: None., (AJTR Copyright © 2021.)

Milling may cause undesired changes in crystal topology, due to exposure of new facets, their corresponding functional groups and surface amorphization. This study investigated effect of milling induced surface amorphous content and chemical environment on moisture sorption behavior of a model hydrophilic drug, Terbutaline Sulphate (TBS). A Dynamic Vapor Sorption (DVS) based analytical method was developed to detect amorphous content, with LOD and LOQ of 0.41% and 1.24%w/w, respectively. The calibration curve gave a linear regression of 0.999 in a concentration range of 0-16.36%w/w amorphous content plotted against surface area normalized % weight change, due to moisture sorption. TBS was milled using air jet mill at 8 Bars for 3 cycles (D 90 - 3.46µm) and analyzed using the validated DVS method prior to and post conditioning. The moisture sorption was higher in case of milled unconditioned TBS. Molecular Dynamics Simulation (MDS) was performed to identify the cause for increased moisture sorption due to altered surface environment or amorphous content. The results implied that the new planes and functional groups exposed on milling had negligible contribution to moisture sorption and the higher moisture sorption in milled unconditioned TBS was due to surface amorphization. Conditioning under elevated humidity recrystallized the milling-induced surface amorphous content and led to decreased moisture sorption in milled conditioned TBS., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objective: This research aimed to investigate the clinical efficacy of aerosol inhalation of ambroxol hydrochloride combined with terbutaline on children with severe pneumonia, and to evaluate its influence on their immune function and inflammatory level., Methods: Totally 113 severe pneumonia children were included. Thereinto, 55 children in the control group (CG) were treated with terbutaline aerosol inhalation, while 58 in the research group (RG) were given ambroxol hydrochloride on the basis of the CG. Their symptom alleviating time, blood gas parameters, adverse reactions during treatment, clinical efficacy, immune function and inflammatory factors were compared., Results: The time of fever clearance time, disappearance of cough and pulmonary rates, chest shadow absorption and hospitalization of children in the RG were shorter than those in the CG. The combined treatment did not increase additional adverse reactions; instead, its effective rate was markedly higher than that in the CG. Further research found that after treatment, the arterial partial pressure of oxygen (PaO 2 ), oxygenation index (OI), CD4+ and CD4+/CD8+, and interleukin-10 (IL-10) levels were dramatically increased, while the arterial partial pressure of carbon dioxide (PaCO 2 ), C-reactive protein (CRP), interleukin-6 (IL-6), interleukin-17 (IL-17) and CD8+ levels were obviously increased. In addition, these indexes of children in the RG were obviously better than those in the CG., Conclusion: Aerosol inhalation of ambroxol hydrochloride combined with terbutaline has a remarkable clinical efficacy on children with severe pneumonia, which can improve their immune function and reduce inflammatory reaction., Competing Interests: None., (AJTR Copyright © 2021.)

Aim: To determine if a policy recommending administration of terbutaline prior to emergency caesarean section improved arterial umbilical cord pH., Materials and Methods: This was a prospective audit between February 2018 and June 2019 among women who underwent a category one or two caesarean section. Neonatal cord gas results and perinatal outcomes were compared before and after the introduction of a policy recommending subcutaneous terbutaline prior to emergency caesarean section., Results: Among 423 women in the pre-policy change cohort and 253 post-policy change, there was no difference in arterial cord pH (median pH = 7.24 before the policy and median pH = 7.24 after the policy was introduced, P = 0.88). There was no statistically significant difference in any perinatal outcome, apart from the median arterial cord lactate which was higher in the post-treatment group (4.2 mmol/L vs 3.9 mmol/L, P = 0.006). Maternal heart rate was higher (median 110 vs 95, P < 0.0001) in the post-treatment group. Breastfeeding was more common in the post-treatment group (99% vs 95%, P = 0.005). There was no difference in estimated blood loss or rate of post-partum haemorrhage. A post hoc analysis according to treatment received, limited to caesarean section when the indication was suspected fetal compromise, demonstrated that among women who received terbutaline the rate of low pH (<7.1) was 3.8% (5/130) when terbutaline was given, compared with 6.6% (18/272) when terbutaline was not given (χ 2 1  = 1.3, P = 0.26)., Conclusion: Changing our labour ward policy to recommending terbutaline prior to all category one and category two caesarean sections did not change arterial cord pH., (© 2020 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.)

Obesity is a chronic low-grade inflammatory condition, and β2-adrenergic agonists as well as exercise have been proposed as anti-inflammatory strategies in obesity, so it is critical to accurately determine the effects of β2-adrenergic stimulation, especially when combined with other non-pharmacological therapies. The aim of this investigation was to determine the effect of β2-adrenergic activation on the inflammatory profile and phenotype of macrophages, and whether these effects could be affected by obesity and exercise in this condition. High-fat diet-induced obese and lean C57BL/6J mice were allocated to sedentary or exercised groups. The inflammatory profiles and phenotypes of their peritoneal macrophages were assessed by flow cytometry in the presence or absence of the selective β2-adrenergic receptor agonist terbutaline. β2-adrenergic activation caused global phenotypic anti-inflammatory effects in lean and obese sedentary mice, which were more drastic (also including anti-inflammatory effects on the cytokine profile) in obese animals. In exercised lean and obese animals, this anti-inflammatory effect is weaker and only evident by decreased iNOS and IL-8 expression, without changes in the anti-inflammatory markers. Therefore, β2-adrenergic activation leads to anti-inflammatory effects, but these effects are modulated by obesity in sedentary conditions, as well as by regular exercise; but not by obesity in trained conditions.

The design of experiments (DoE) is one of the quality-by-design tools valued in analytical method development, not only for cost reduction and time effectiveness, but also for enabling analytical method control and understanding via a systematic workflow, leading to analytical methods with built-in quality. This work aimed at using DoE to enhance method understanding for a developed UHPLC enantioseparation of terbutaline (TER), a model chiral drug, and to define quality assurance parameters associated with using chiral mobile phase additives (CMPA). Within a response surface methodology workflow, the effect of different factors on both chiral resolution and retention was screened and optimized using Plackett-Burman and central composite designs, respectively, followed by multivariate mathematical modeling. This study was able to delimit method robustness and elucidate enantiorecognition mechanisms involved in interactions of TER with the chiral modifiers. Among many CMPAs, successful TER enantioresolution was achieved using hydroxypropyl β-cyclodextrin (HP-β-CD) added to the mobile phase as 5.4 mM HP-β-CD in 52.25 mM ammonium acetate. Yet, limited method robustness was observed upon switching between the different tested CMPA, concluding that quality can only be assured with specific minimal pre-run conditioning time with the CMPA, namely 16-column volume (60 min at 0.1 mL/min). For enantiorecognition understanding, computational molecular modeling revealed hydrogen bonding as the main binding interaction, in addition to dipole-dipole inside the CD cavity for the R enantiomer, while the S enantiomer was less interactive.

Recently, the β 2 -adrenoceptor agonist terbutaline was shown to have α 1 -adrenolytic activity in mouse isolated pulmonary arteries in vitro and to lower pulmonary artery pressure in anaesthetised mice. The aim of our study was to determine the α 1 -adrenoceptor antagonist activity of terbutaline and its structurally close resorcinol, orciprenaline, in rat isolated small mesenteric arteries set up for myography. Their α 1 -adrenoceptor antagonist potency was then compared with their potency as β 2 -adrenoceptor agonists. Concentration-response curves to methoxamine were competitively antagonised by terbutaline (30-300 μM) or orciprenaline (30-300 μM) with a pK B of 4.70 ± 0.09 or 4.79 ± 0.17, respectively. Both terbutaline and orciprenaline fulfilled the criteria for simple, silent competitive antagonism. Terbutaline (30-300 μM) had no effect on endothelin-1 concentration-contraction curves. Our findings suggest that after oral dosing of terbutaline, the maximum plasma levels would NOT reach levels to show α 1 -adrenoceptor antagonist activity. In conclusion, our work has provided additional quantitative evidence that terbutaline and orciprenaline are weak competitive α 1 -adrenoceptor antagonists, but this additional property is probably not therapeutically important in the clinical treatment of asthma or pulmonary artery hypertension with these more potent β 2 -adrenoceptor agonists., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The major goal of this study was to determine the affinity pattern of the terbutaline (TB) enantiomers toward α-, β-, γ-, and heptakis(2,3-di-O-acetyl)-β-cyclodextrins and using NMR spectroscopy for the understanding of the fine mechanisms of interaction between the cyclodextrins (CD) and TB enantiomers. It was shown once again that CE in combination with NMR spectroscopy represents a sensitive tool to study the affinity patterns and structure of CD complexes with chiral guests. Opposite affinity patterns of TB enantiomers toward native α- and β-CDs were associated with significant differences between the structure of the related complexes in solution. In particular, the complex between TB enantiomers and α-CD was of the external type, whereas an inclusion complex was formed between TB enantiomers and β-CD. One of the possible structures of the complex between TB and heptakis(2,3-di-O-acetyl)-β-CD (HDA-β-CD) was quite similar to that of TB and β-CD, although the chiral recognition pattern and enantioselectivity of TB complexation with these two CDs were very different., (© 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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.