Salbutamol Research Articles

Literature-based Comparative Study between Herbal and Synthetic Mucolytics

Abstract: Coughing and sneezing are the body’s reflexes to various acute and chronic respiratory illnesses like asthma, COPD, lung cancer, etc. : Mucus is a sticky, gelatinous material produced by the mucus gland to protect the airways. Mucolytics, antitussives and expectorants may help in treating hypersecretion of mucin that may lead to cough, cystic fibrosis, asthma, and COPD. Mucolytics if given along with the drugs like corticosteroids, albuterol sulphate, and levalbuterol HCl in asthma and for the management of COPD like corticosteroids and bronchodilators, may help in loosening the viscosity of the mucus and clearing it out. : Mucolytics can be synthetic or herbal in origin and work by one of the three processes, viz. enzymatic degradation, disulphide bond cleavage and calcium chelation. Mucolytics breaks down mucin structure and loosen the mucus, helping it to expel out from the body. Some examples of synthetic mucolytics are Bromhexine and N-acetylcysteine. Herbal mucolytics have traditionally been used for the treatment of cough by indigenous people of India. Malva sylvestris, Zizyphus vulgaris are some of the examples of herbal mucolytics.

Salbutamol ameliorates skeletal muscle wasting and inflammatory markers in streptozotocin (STZ)-induced diabetic rats

Diabetes accelerates muscle atrophy, leading to the deterioration of skeletal muscles. This study aimed to assess the potential of the β2-adrenoceptor agonist, salbutamol (SLB), to alleviate muscle atrophy in streptozotocin (STZ)-induced diabetic rats. Male Sprague Dawley rats were randomized into four groups (n=6): control, SLB, STZ (55 mg/kg, single i.p.), and STZ + SLB (6 mg/kg, orally for 4 weeks). After the final SLB dose, animals underwent tests to evaluate muscle strength and coordination, including forelimb grip strength, wire-hanging, actophotometer, rotarod, and footprint assessments. Rats were then sacrificed, and serum and gastrocnemius (GN) muscles were collected for further analysis. Serum evaluations included proinflammatory markers (tumor necrosis factor α, interleukin-1β, interleukin-6), muscle markers (creatine kinase, myostatin), testosterone, and lipidemic markers. Muscle oxidative stress (malonaldehyde, protein carbonyl), antioxidants (glutathione, catalase, superoxide dismutase), and histology were also performed. Additionally, 1H nuclear magnetic resonance serum profiling was conducted. SLB notably enhanced muscle grip strength, coordination, and antioxidant levels, while reduced proinflammatory markers and oxidative stress in STZ-induced diabetic rats. Reduced serum muscle biomarkers, increased testosterone, restored lipidemic levels, and improved muscle cellular architecture indicated SLB's positive effect on muscle condition in diabetic rats. Metabolomics profiling revealed that the STZ group significantly increased the phenylalanine-to-tyrosine ratio (PTR), lactate-to-pyruvate ratio (LPR), acetate, succinate, isobutyrate, and histidine. SLB administration restored these perturbed serum metabolites in the STZ-induced diabetic group. In conclusion, salbutamol significantly protected against skeletal muscle wasting in STZ-induced diabetic rats.

Acute Effects of Single Versus Combined Inhaled β2-Agonists Salbutamol and Formoterol on Time Trial Performance, Lung Function, Metabolic and Endocrine Variables

BackgroundHigh prevalence rates of β2-agonist use among athletes in competitive sports makes it tempting to speculate that illegitimate use of β2-agonists boosts performance. However, data regarding the potential performance-enhancing effects of inhaled β2-agonists and its underlying molecular basis are scarce.MethodsIn total, 24 competitive endurance athletes (12f/12m) participated in a clinical double-blinded balanced four-way block cross-over trial to investigate single versus combined effects of β2-agonists salbutamol (SAL) and formoterol (FOR), to evaluate the potential performance enhancement of SAL (1200 µg, Cyclocaps, Pb Pharma GmbH), FOR (36 µg, Sandoz, HEXAL AG) and SAL + FOR (1200 µg + 36 µg) compared to placebo (PLA, Gelatine capsules containing lactose monohydrate, Pharmacy of the University Hospital Ulm). Measurements included skeletal muscle gene and protein expression, endocrine regulation, urinary/serum β2-agonist concentrations, cardiac markers, cardiopulmonary and lung function testing and the 10-min time trial (TT) performance on a bicycle ergometer as outcome variables. Blood and urine samples were collected pre-, post-, 3 h post- and 24 h post-TT.ResultsMean power output during TT was not different between study arms. Treatment effects regarding lung function (p < 0.001), echocardiographic (left ventricular end-systolic volume p = 0.037; endocardial global longitudinal strain p < 0.001) and metabolic variables (e.g. NR4A2 and ATF3 pathway) were observed without any influence on performance. In female athletes, total serum β2-agonist concentrations for SAL and FOR were higher. Microarray muscle gene analysis showed a treatment effect for target genes in energy metabolism with strongest effect by SAL + FOR (NR4A2; p = 0.001). Of endocrine variables, follicle-stimulating hormone (3 h Post–Post-TT), luteinizing hormone (3 h Post–Pre-TT) and insulin (Post–Pre-TT) concentrations showed a treatment effect (all p < 0.05).ConclusionsNo endurance performance-enhancing effect for SAL, FOR or SAL + FOR within the permitted dosages compared to PLA was found despite an acute effect on lung and cardiac function as well as endocrine and metabolic variables in healthy participants. The impact of combined β2-agonists on performance and sex-specific thresholds on the molecular and cardiac level and their potential long-term performance enhancing or health effects have still to be determined.Trial registration: Registered at Eudra CT with the number: 2015-005598-19 (09.12.2015) and DRKS with number DRKS00010574 (16.11.2021, retrospectively registered).

Fluorescence immunoassay for simultaneous detection typical β-agonists in animal derived food using blue-green upconversion nanoparticles as labels

Common typical β-agonists mainly include ractopamine (RAC), salbutamol (SAL), and clenbuterol (CLB). In view of the harm to human health causes by the ingestion of animal derived food containing β-agonists, and a series of regulations have been issued to restrict the usage of β-agonists as growth promoters. In this work, a fluorescence immunoassay is developed for the simultaneous detection of typical β-agonists based on blue-green upconversion nanoparticles (UCNPs) combine with magnetic separation. Here, blue-green UCNPs act as a signal amplification source, and magnetic polystyrene microspheres (MPMs) act as an ideal separation medium. Based on a competitive form, capture probe competes (RAC-OVA@MPMs and SAL-OVA@MPMs) with targets to bind corresponding signal probe (anti-RAC antibody@NaYF4:Yb, Tm UCNPs and anti-SAL antibody@NaYF4:Yb, Er UCNPs). The fluorescence difference values of the competitive immune-complex obtained via magnetic separation at 483 nm and 550 nm are proportional to concentrations of RAC and SAL, respectively. The immunoassay has the wide detection linear range from 0.001 to 100 μg L−1, and the low limit of detection (LOD) is 5.04 × 10−4 μg L−1 for RAC, 1.97 × 10−4 μg L−1 for SAL, respectively. Meanwhile, use of antibody with same recognition ability for SAL and CLB makes that the fluorescence immunoassay can achieve simultaneous detection of three typical β-agonists (RAC, SAL, and CLB). This fluorescence immunoassay has good application value and practicability for simultaneous detection of typical β-agonists in animal derived food.

Salbutamol Attenuates Diabetic Skeletal Muscle Atrophy by Reducing Oxidative Stress, Myostatin/GDF-8, and Pro-Inflammatory Cytokines in Rats.

Type 2 diabetes is a metabolic disorder that leads to accelerated skeletal muscle atrophy. In this study, we aimed to evaluate the effect of salbutamol (SLB) on skeletal muscle atrophy in high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic rats. Male Sprague Dawley rats were divided into four groups (n = 6): control, SLB, HFD/STZ, and HFD/STZ + SLB (6 mg/kg orally for four weeks). After the last dose of SLB, rats were assessed for muscle grip strength and muscle coordination (wire-hanging, rotarod, footprint, and actophotometer tests). Body composition was analyzed in live rats. After that, animals were sacrificed, and serum and gastrocnemius (GN) muscles were collected. Endpoints include myofibrillar protein content, muscle oxidative stress and antioxidants, serum pro-inflammatory cytokines (interleukin-1β, interleukin-2, and interleukin-6), serum muscle markers (myostatin, creatine kinase, and testosterone), histopathology, and muscle 1H NMR metabolomics. Findings showed that SLB treatment significantly improved muscle strength and muscle coordination, as well as increased lean muscle mass in diabetic rats. Increased pro-inflammatory cytokines and muscle markers (myostatin, creatine kinase) indicate muscle deterioration in diabetic rats, while SLB intervention restored the same. Also, Feret's diameter and cross-sectional area of GN muscle were increased by SLB treatment, indicating the amelioration in diabetic rat muscle. Results of muscle metabolomics exhibit that SLB treatment resulted in the restoration of perturbed metabolites, including histidine-to-tyrosine, phenylalanine-to-tyrosine, and glutamate-to-glutamine ratios and succinate, sarcosine, and 3-hydroxybutyrate (3HB) in diabetic rats. These metabolites showed a pertinent role in muscle inflammation and oxidative stress in diabetic rats. In conclusion, findings showed that salbutamol could be explored as an intervention in diabetic-associated skeletal muscle atrophy.

Development of Nafion/single-walled carbon nanotube integrated arrays for the rapid detection of salbutamol doping.

Salbutamol (SAL), a drug originally intended for the treatment of bronchial and pulmonary diseases, has repeatedly been used for doping in competitive sports. Herein, an integrated array (NFCNT array) that prepared by template-assisted scalable filtration using Nafion-coated single-walled carbon nanotube (SWCNT) is presented for the rapid field detection of SAL. Spectroscopic and microscopic measurements were used to confirm the introduction of Nafion onto the surface of the array and to analyze the resulting morphological changes. The effects of Nafion addition on the resistance and electrochemical properties of the arrays (e.g., the electrochemically active area, charge-transfer resistance, and adsorption charge) are also discussed in depth. With an electrolyte/Nafion/SWCNT interface and moderate resistance, the NFCNT-4 array prepared containing 0.04wt% Nafion suspension exhibits the greatest voltammetric response to SAL. Subsequently, a possible mechanism for the oxidation of SAL was proposed, and a calibration curve in the range of 0.1-15 μM was established. Finally, the NFCNT-4 arrays were applied to the detection of SAL in human urine samples with satisfactory recoveries.

A computational study of droplet-spray formation from pressurized metered dose inhalers with applications to drug deposition in a human lung-airway model

Orally administered drugs using portable devices, such as pressurized metered dose inhalers (pMDIs), can alleviate the symptoms of various respiratory diseases. The basic non-isothermal fluid-particle dynamics of pMDIs have been simulated, including computer model validations and different inhalation techniques, using the Ventolin HFA from GlaxoSmithKline (UK) as a representative application. Specifically, the evolution of thermal droplet sprays has been realistically simulated and experimentally validated, employing the open-source computational fluid dynamics (CFD) toolbox OpenFOAM. The segmental droplet temperature results show elevated temperatures for higher inhalation flow rates because of stronger convective flow around the evaporating droplets. The general problems of high, wasteful oropharyngeal deposition and cold impacting droplets were tackled by devising a new ‘pulsed injection’ strategy in which the spray was broken into pulses with a time delay between them. This new methodology indicated up to a 20% increase in useful lung deposition beyond the oropharynx over conventional drug administration methods. In addition, compared to the conventional single injection approach, the segmental variations in temperature of the deposited aerosols show an increase in temperature of around 10% and 7% for the 30 LPM and 60 LPM cases up to segment 4 for pulsed injection. An increase of 23% and 13% for the 30 LPM and 60 LPM cases were observed for segments 5–7 for pulsed injection. Also, a reduction in inertia of the droplets at 30 LPM, where the spray was broken into eight pulses with 100 ms delay between them, resulted in higher residence times and an increase in temperature of over 35°C.Copyright © 2023 American Association for Aerosol Research

Iridium (IV) oxide-mediated microorganism nanozyme amplified immunochromatographic assay for dual-signal sensitive detection of salbutamol

Salbutamol (SAL) residues in edible animal tissues have various adverse effects on human health after digestion. Herein, we constructed an innovative functionalized microorganism nanozyme-mediated immunochromatographic assay for sensitive and accurate dual-colorimetric detection of SAL by introducing the Yeast@IrO 2 as bifunctional signal tag. The Yeast@IrO 2 was synthesized by self-assembling iridium (IV) oxide nanoparticles (IrO 2 NPs) on the surface of inactivated yeast cells, which showed high monodispersity, uniform shapes, preeminent biocompatibility and rapid antibodies labeling capacity. After reaction for 15 min, through further employing [3,3′,5,5’ Tetramethylbenzidine (TMB) and hydrogen peroxide (H 2 O 2 )] as substrate to trigger the color reaction, the developed biosensor performed with outstanding performance, including limit of detection (0.012 ng/mL), linearity (R 2 > 0.99) and selectivity. Concurrently, the visual limit of detection (0.2 μg/kg) and satisfactory recoveries (85.6%–103.9%) were obtained by monitoring SAL in pig liver and beef samples. Briefly, this work provided a universal platform for sensitive, precise and rapid detection of toxic and hazardous substances in food safety fields. • A microorganism nanozyme-mediated ICA was developed to detect salbutamol. • The Yeast@IrO 2 was designed by self-assembling IrO 2 NPs on inactivated yeast cells. • The Yeast@IrO 2 generated colorimetric- and catalytic-based dual signals. • The sensor showed lower detection limit (0.012 ng/mL) and broader detection range. • The sensor could be applied to the detection of SAL in beef and pig liver samples.

Combinatory in vitro effects of the β2-agonists salbutamol and formoterol in skeletal muscle cells

β2-agonists are used for the treatment of bronchoconstriction, but also abused in doping. Beside an ergogenic activity β2-agonists may have also anabolic activity. Therefore, we investigated the anabolic activity and associated molecular mechanisms of Salbutamol (SAL) and Formoterol (FOR) alone, as well as in combination in C2C12 myotubes. In differentiated C2C12 cells, dose-dependent effects of SAL and FOR (alone/in combination) on myotube diameter, myosin heavy chain (MHC) protein expression and the mRNA expression of genes involved in hypertrophy were analyzed. β2-adrenoceptor 2 (ADRB2), androgen receptor (AR) and estrogen receptor (ER) inhibitors, as well as dexamethasone (Dexa) were co-incubated with the β2-agonists and myotube diameter was determined. SAL and FOR treatment significantly induced hypertrophy and increased MHC expression and the mRNA expression of Igf1, mTOR, PIk3r1 and AMpKa2. In contrast to an ER inhibitor, the ADRB2 and AR inhibitors, as well as Dexa antagonized FOR and SAL induced hypertrophy. Combined treatment with SAL and FOR resulted in significant additive effects on myotube diameter and MHC expression. Future clinical studies are needed to prove this effect in humans and to evaluate this finding with respect to antidoping regulations.

Electron beam degradation of the cardiovascular drug salbutamol: Mechanisms and degradation pathways

With the increasing incidence and mortality of cardiovascular diseases, high consumption of the cardiovascular drug salbutamol (SAL) has made this compound an emerging pollutant in natural water and a challenge for traditional wastewater treatment. In this paper, an efficient advanced oxidation process was used to degrade SAL by electron beam (EB) irradiation. The results revealed that 100 mg L−1 of SAL could be nearly completely removed (95.1%) at 10 kGy and the degradation kinetic well followed pseudo first-order kinetic model. Different factors, including pH, inorganic ions and water matrix, had varying effects on the degradation of SAL owing to their important influence on the formation of reactive species in the aqueous solution. And it was found that eaq− played a major role in the degradation of SAL parent. Moreover, the addition of K2S2O8 (20 mM) increased the SAL mineralization rate from 2.9% to 64.2%, suggesting that oxidation free radicals could greatly improve the mineralization rate of SAL. Combining with the theoretical calculations and determined degradation by-products, four possible degradation pathways of SAL by EB irradiation were proposed, including H•, •OH and eaq− all participated in the degradation of SAL. Finally, toxicity evaluation suggested that the toxicity of SAL aqueous solution reduced after EB irradiation, indicating that it is an effective method to degrade SAL.

An Analysis of Prehospital Pediatric Medication Dosing Errors after Implementation of a State-Wide EMS Pediatric Drug Dosing Reference

Background Medication dosing errors are common in prehospital pediatric patients. Prior work has shown the overall medication error rate by emergency medical services (EMS) in Michigan was 34.7%. To reduce these errors, the state of Michigan implemented a pediatric dosing reference in 2014 listing medication doses and volume to be administered. Objective To examine changes in pediatric dosing errors by EMS in Michigan after implementation of the pediatric dosing reference. Methods We conducted a retrospective review of the Michigan Emergency Medical Services Information System of children ≤ 12 years of age from June 2016–May 2017 treated by 16 EMS agencies. Agencies were a mix of public, private, third-service, and fire-based. A dosing error was defined as >20% deviation from the weight-appropriate dose listed on the pediatric dosing reference. Descriptive statistics with confidence intervals and standard deviations are reported. Results During the study period, there were 9,247 pediatric encounters, of whom 727 (7.9%) received medications and are included in the study. There were 1078 medication administrations, with 380 dosing errors (35.2% [95% CI 25.3–48.4]). The highest error rates were for dextrose 50% (3/4 or 75% [95% CI 32.57–100.0]) and glucagon (3/4 or 75% [95% CI 32.57–100.0]). The next highest proportions of incorrect doses were opioids: intranasal fentanyl (11/16 or 68.8% [95% CI 46.04–91.46]) and intravenous fentanyl (89/130 or 68.5% [95% CI 60.47–76.45]). Morphine had a much lower error rate (24/51 or 47.1% [95% CI 33.36–60.76]). Midazolam had the third highest error rate, for intravenous (27/50 or 54.0% [95% CI (40.19–67.81]) and intramuscular (25/68 or 36.8% [95% CI 40.19–67.81]) routes. Epinephrine 1 mg/10 ml had an incorrect dosage rate of 35/119 (29.4% [95% CI 20.64–36.99]). Asthma medications had the lowest rate of incorrect dosing (albuterol sulfate 9/247 or 3.6% [95% CI 1.31–5.98]). Conclusions Medications administered to prehospital pediatric patients continue to demonstrate dosing errors despite pediatric dosing reference implementation. Although there have been improvements in error rates in asthma medications, the overall error rate has increased. Continued work to build patient safety strategies to reduce pediatric medication dosing errors by EMS is needed.

The Utility of Spirometry in Assessment of Presumptive Diagnosis of Bronchial Asthma in a Nigerian Tertiary Hospital

Context: Spirometry with reversibility testing is the gold standard for definitive diagnosis of bronchial asthma. However, even in those with established bronchial asthma reversibility test result may subsequently become negative. Spirometry results may also be normal during exacerbation-free intervals. Aims: This study assessed the role of spirometry in diagnostic evaluation of bronchial asthma and determined the ventilatory patterns of patients with presumptive diagnosis of bronchial asthma using spirometry and the proportion of those who showed positive reversibility test. Patients and Methods: This was a retrospective study carried out at a teaching hospital in Nigeria. This was an audit of consecutive patients with presumptive diagnosis of asthma referred for spirometry between January 2013 and June 2015. Spirometer with disposable mouthpieces, stadiometer, and salbutamol inhalers were used. The statistical analysis was done with Statistical Package for the Social Sciences version 20. Results: Eighty-nine participants did spirometry of whom 28 (31.5%) had additional postbronchodilator testing. Fifty (56.3%) participants were females (mean age of 42.17 ± 15.48 years). Normal, obstructive, restrictive, and mixed ventilatory patterns were found in 39 (43.8%), 31 (34.8%), 10 (11.2%), and 9 (10.1%) participants, respectively. Positive reversibility test result occurred in 15 (53.6%) participants, 9/19 obstructive (47.4%), and 6/9 mixed patterns (66.7%). Conclusion: Only a few patients with presumptive diagnosis of asthma were confirmed by spirometry. Spirometry is useful in asthma diagnosis, but clinicians should be aware of its limitations in diagnostic assessment. Although asthma is typically associated with obstructive spirometry, other spirometry patterns can occur.

A SERS/electrochemical dual-signal readout immunosensor using highly-ordered Au/Ag bimetallic cavity array as the substrate for simultaneous detection of three β-adrenergic agonists

A surface-enhanced Raman scattering (SERS)/electrochemical dual-signal readout immunosensor was developed for simultaneous detection of β-adrenergic agonists salbutamol (SAL), ractopamine (RAC) and phenylethanolamine A (PA). The highly-ordered gold/silver bimetallic cavity array (BMCA) was prepared by electrodepositing Au/Ag nanoparticles to the interstice of highly ordered close-packed polystyrene templates. After electrochemical and SERS characterization, the BMCA was used as the substrate for constructing SERS/electrochemical dual-signal readout immunosensor. 3,3′,5,5′-tetramethylbenzidine (TMB), methylene blue (MB) and Nile blue (NB) were selected as the dual-signal reporters, and hybridization chain reaction (HCR) was used as the signal amplifier. The immunoprobe was prepared by absorption of the antibody (Ab) and constructing HCR system embedded with electro/SERS reporter on Au nanoparticles (NPs). After competitive immuno-reaction between coating antigen and analyte for limited Ab on immunoprobe, the SERS/electrochemical dual-signals on BMCA were measured for quantitatively detecting SAL, RAC and PA simultaneously. SAL, RAC and PA were detected in concentration range of 1 pg mL−1 to 100 ng mL−1 with LOD of 0.8, 0.4, and 1.3 pg mL−1, respectively. The applicability of the proposed immunosensor in spiked pork liver samples was verified by the recovery of 95.0%–108.5% with RSD of 6.9%–10.7%. It was proven that the immunosensor was able to detect multiple β-adrenergic agonists with high sensitivity, specificity, accuracy and precision. The immunosensor can be used as a platform for the determination of other small molecular compounds in biological, food and environmental analytical fields.

Using Filters to Estimate Regional Lung Deposition with Pressurized Metered Dose Inhalers.

To evaluate the suitability of a recently proposed apparatus that uses filters to directly fractionate the in vitro lung dose into regional deposition estimates for use with pressurized metered dose inhaler (pMDI) devices as a less resource intensive alternative to cascade impaction. Using three commercially available pMDI devices (Asmanex HFA, Ventolin HFA, QVAR), regional deposition estimates were measured directly using the filter-based apparatus (FBA). Regional deposition estimates were also generated for the same inhalers by performing cascade impaction measurements and inputting the results to an in silico regional deposition model. Regional deposition for each inhaler was evaluated at an inhalation flow rate of 30 and 60 L/min. Total recovery of active pharmaceutical ingredient and extrathoracic deposition was independent of method used. The regional deposition estimates provided by each method were similar and captured the same trends. The direct measurement of estimated regional deposition is possible when using the FBA. This method is far less resource intensive than existing methods and so may be useful both for comparison of generic alternatives and the development of innovative products.

A potential sensor for assessing thorium (IV) based on Albuterol sulfate fluorescence enhancement: A density functional theory (DFT) study

• Introducing a new fluorescent sensor for assessing Th(IV) in environmental samples. • Fluorescence mechanism was discussed. • HOMO and LUMO energy levels has been calculated by DFT. This study introduces a potential fluorescence sensor for assessing thorium (Th(IV)) in aquatic environments. In the presence of Th(IV), Albuterol Sulfate ( ABS ) 4-[2-( tert -butylamino)-1-hydroxyethyl]-2-(hydroxymethyl)phenol; sulfuric acid exhibits significant fluorescence enhancement at 600 nm. The current ABS ligand sensor shows wide linear range from 6.0 × 10 −8 – 2.5 × 10 −7 mol/L and pH range of 4–6. Interestingly, when all evaluated interference ions coexisted, the change in fluorescence emission intensity of ABS -Th complex was roughly 2.3 %. The binding mode is studied and indicating a 2:1 complex formation between ABS ligand and Th (IV). Density functional theory (DFT) has been utilized to examine the interaction characteristics between the present ABS ligand sensor and Th(IV) and to compute the geometric configuration of the ABS and ABS -Th through the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energy levels. The interaction properties exhibit considerable effect on the HOMO and LUMO properties of the complexes, as well as a fluorescence enhancement that could be attributable to the heavy atom effect of Th (IV). The ABS sensor shows remarkable features and provides good performance compared to some of the optical sensors, making it a potential new fluorescence sensor for Th(IV) assessment.

Compliance to a Standardized Protocol for Stock Albuterol Medication among School Staff.

A stock inhaler program provided access to rescue medication (albuterol sulfate) for school children. School staff were provided with a standardized protocol for medication administration. We hypothesized licensed nurses were more likely to report compliant events compared to unlicensed school staff. Stock inhaler events were defined as either compliant or non-compliant. A school protocol compliance score was calculated using the total number of compliant events divided by the total number of all events. The protocol for administration indicated 4 puffs for mild respiratory distress and 8 puffs for severe respiratory distress; therefore, events were defined as compliant if the dose of medication was divisible by 4. A Cragg Poisson hurdle regression was used to examine the association between compliance score and school staff experience. One-hundred fifty-two schools reported 999 stock inhaler events. Of these events, 28% were compliant and 72% of events were non-compliant. After controlling for school organizational type, grades served, and school size, school staff experience was not predictive of protocol compliance. Future efforts should focus on improving protocol compliance among licensed nurses and unlicensed school staff.

Effect of inhaled albuterol on whole blood potassium concentrations in dogs.

Albuterol by inhalation (IH) is a common treatment for hyperkalemia in humans but its effect on blood potassium concentrations in dogs is unknown. Determine whether albuterol (IH) decreases blood potassium concentrations in healthy normokalemic dogs and if effects are dose-dependent. Ten healthy dogs. Prospective, crossover experimental study. Albuterol sulfate was administered at a low-dose (90 μg) in phase I and, 7 days later, high-dose (450 μg) in phase II. Blood potassium and glucose concentrations (measured via blood gas analyzer) and heart rates were obtained at baseline and then 3, 5, 10, 15, 30, 60, 90, 120, 180, and 360 minutes after inhaler actuation. Blood potassium concentrations decreased rapidly after albuterol delivery with a significant reduction compared to baseline within 30 minutes in both phases (P=.05). The potassium nadir concentration of phase I occurred at 60 minutes (mean, SD; 4.07 mmol/L, 0.4) and was significantly decreased from baseline, (4.30 mmol/L, 0.3; t(9)=2.40, P=.04). The potassium nadir concentration of phase II occurred at 30 minutes (mean, SD; 3.96 mmol/L, 0.39) and was also significantly decreased from baseline, (4.33 mmol/L, 0.4; t(9)=2.22, P=.05). The potassium nadir concentration decreased by 0.1 mmol/L for each 10μg/kg increase in dose of albuterol (P=.01). Five dogs had ≥1 hyperglycemic measurement (ie, >112 mg/dL). No median heart rate was tachycardic nor was any mean blood glucose concentration hyperglycemic at any time point. Albuterol IH decreases blood potassium concentrations in a dose-dependent manner without clinically meaningful alterations to heart rate or blood glucose concentrations in healthy dogs. The mean decrease in potassium concentration at the high-dose of albuterol was modest (0.38 mmol/L).

Isoprenaline and salbutamol inhibit pyroptosis and promote mitochondrial biogenesis in arthritic chondrocytes by downregulating β-arrestin and GRK2.

Rheumatoid arthritis and osteoarthritis overlap many molecular mechanisms of cartilage destruction. Wear and tear in cartilage is chondrocyte-mediated, where chondrocytes act both as effector and target cells. In current study, role of β2-AR was studied in chondrocytes both in vitro and in vivo. High grade inflammation in vitro and in vivo disease models led to decline in anti-inflammatory β2-AR signaling and use of β2-AR agonist attenuated arthritis symptoms. Detailed analysis in chondrocytes revealed that Isoprenaline (ISO) and Salbutamol (SBT) increased cell viability and relative Bcl-2 expression, meanwhile, decreased proteins levels of TNF-α, IL-6 and IL-8 in arthritic chondrocytes when compared with control, respectively. SBT preserved physiological concentration of antioxidant enzymes (CAT, POD, SOD and GSH) in cartilage homogenates and ISO inhibited IL-1β-mediated genotoxicity in arthritic chondrocytes. Moreover, β2-AR agonist increased mitochondrial biogenesis and proteoglycan biosynthesis by upregulating the gene expression of PGC1-α, NRF2 and COL2A1, Acan, respectively. ISO and SBT inhibited extracellular matrix (ECM) degradation by downregulating the gene expression of MMP1, MMP3, MMP9 and ADAMTS5 in vitro and in vivo study. In mechanism, β2-AR agonists decreased β-arrestin and GRK2 pathway, and as a result mice receiving SBT did not exhibit severe disease. Hence our data suggest β2-AR agonist administered at disease onset can inhibit receptor internalization by downregulating the expression of β-arrestin and GRK2 in chondrocytes.

Intermittent Tiotropium Bromide for Episodic Wheezing: A Randomized Trial.

Options to treat and prevent episodic wheezing in children are scarce. Our objective was to assess the efficacy of intermittent tiotropium bromide treatment in early childhood episodic wheezing. This 48-week, randomized, open-label, controlled, parallel-group trial was conducted at 4 hospitals in Finland. Children aged 6 to 35 months with 2 to 4 physician-confirmed episodes of wheeze and/or shortness of breath were considered eligible. Study participants were randomly allocated to receive 1 of 3 treatments: once-daily tiotropium bromide 5 µg for 7 to 14 days during respiratory tract infections and as-needed albuterol sulfate 0.2 mg (n = 27), twice-daily fluticasone propionate 125 µg for 7 to 14 days during respiratory tract infections and as-needed albuterol sulfate 0.2 mg (n = 25), or as-needed albuterol sulfate 0.2 mg alone (n = 28). The primary outcome was efficacy, assessed as intention-to-treat by comparing the proportion of episode-free days (the days lacking symptoms or treatments) between the treatment groups. The proportion of episode-free days was higher in those receiving intermittent tiotropium bromide (median 97% [interquartile range, 93% to 99%]) than in those receiving intermittent fluticasone propionate (87% [78% to 93%], P = .002), or with as-needed albuterol sulfate alone (88% [79% to 95%], P = .003). Adjustment with allergic sensitization, the baseline number of physician-confirmed episodes of wheeze and/or shortness of breath, or short-course glucocorticoid treatment in the 2 weeks before the enrollment, did not affect the result. Intervention-related adverse events were not seen. Intermittent tiotropium bromide treatment may be an effective alternative to current therapies for episodic wheezing. Before implementation of use, further research on safety and efficacy is indicated.

Sensitive and simultaneous detection of ractopamine and salbutamol using multiplex lateral flow immunoassay based on polyethyleneimine-mediated SiO2@QDs nanocomposites: Comparison and application

The abuse of illegal additives poses a severe threat to human health. As such, it is of great significance to develop a simple, rapid and high-throughput analysis method for ensuring food safety from source to terminal. Herein, we proposed a multiplex fluorescent lateral flow immunoassay (LFIA) using the nanoassembly of silicon dioxide (SiO2) and quantum dots (QDs) as the advanced signal probe that can simultaneously detect ractopamine (RAC) and salbutamol (SAL) in swine urine and pork samples, and compared with other four conventional labels. The core–shell SiO2@QDs nanocomposites with strong luminescence, high stability, and abundant surface carboxyl groups were conjugated with antibodies to form high-performance SiO2@QDs immunoprobes, which improve the sensitivity and reliability of the LFIA. The developed SiO2@QDs-based LFIA achieved simultaneous detection of RAC and SAL in one strip within 13 min, with the limit of detection at 0.007 ng/mL and 0.032 ng/mL, respectively. The sensitivity of SiO2@QDs was superior to gold nanoparticles (AuNPs) and fluorescent microspheres (FMs), and exhibited comparative sensitivity with time-resolved microspheres (TRFMs), while overcoming the shortcomings of QDs that tend to aggregate. The recoveries in spiked swine urine and pork samples ranged from 73.7 to 111.0% with relative standard deviations between 4.7% and 15.5%. Good correlations were observed between the SiO2@QDs-based LFIA and commercial enzyme-linked immunosorbent assay for RAC (R2 = 0.936) and SAL (R2 = 0.979) detection. Briefly, the proposed method could be a promising screening on-site tool for convenient, rapid and sensitive detection of multiple illegal additives residues from the source to the terminal in food safety.