Acute urticaria is a condition characterized by the rapid onset of raised, itchy welts, often triggered by various factors. This report presents a case of acute urticaria that may be related to excessive intake of nicotine from smoking cessation lozenges. The patient had consumed a large amount of smoking cessation lozenges (containing nicotine) 3 days before the onset of symptoms, which was suspected to be caused by nicotine overdose. But, the association between nicotine overdose and acute urticaria is hypothetical and cannot be confirmed based on a single case. Following 10 days of treatment with intravenous methylprednisolone, pantoprazole, nebulized terbutaline and dexamethasone, and oral antihistamines, the patient improved significantly and was discharged.

Background/Objectives: Packing, flow, and aerosolization properties of a series of binary adhesive mixtures containing micronized or spray-dried drugs were investigated, and the relationships between these blend properties and the blend structure were studied. Methods: Micronized or spray-dried terbutaline sulfate and salbutamol sulfate were used as model drugs, and an α-lactose powder was used as the carrier. Binary mixtures with drug loads ranging from 2 to 20% were prepared. The bulk density, compressibility, permeability, and shearing properties of the carrier powder and mixtures were determined, along with the in vitro aerosolization propensity of the mixtures using two types of inhalers. Imaging of the mixtures was used to assess the blend structure. Conclusions: The particle engineering method gave differences in particle crystallinity and morphology. The development of the adhesive layer with drug load was broadly consistent with the blend state concept. Spray-dried particles, however, exhibited a higher propensity to localize within surface cavities on the carrier and produced a more voluminous enveloped adhesive layer. The spray-dried particles gave a higher bulk density, a lower Hausner ratio, comparable shear strength, and a lower angle of internal friction. Aerosolization performance, including metrics such as fine particle fraction (FPF), depended on inhaler design; nevertheless, for both inhalers, aerosolization behavior was influenced by blend state and physicochemical properties of the drug. At low drug loads, spray-dried particles dispersed to a lower degree, while at high drug loads, the dispersion performance of the two particle types converged. For example, at an intermediate drug load of 7.4%, the FPF was about 20% for the spray-dried drugs and about 30% for the micronized drugs using the Screenhaler device, while the corresponding FPF:s were about 25% and 50% for spray-dried drugs and 40% and 55% for crystalline drugs using the Monodose inhaler. Overall, the physical characteristics of the drug particles were found to influence the structural evolution of the blends, as well as their mechanical and aerosolization properties.

Sympathetic noradrenergic stimuli are transduced at the systemic and cellular level through multiple adrenergic receptor subtypes, the predominant of which is the β2-adrenoceptor (β2-AR). In female-specific hormone-sensitive cancers like breast cancer, the effects of adrenergic stimulation and altered hormone sensitivity on cancer cell survival signaling in the context of estrogen receptor (ER) status-dependent cellular responsiveness remain incompletely understood. ER-positive (MCF-7) and ER-negative (MDA-MB-231) breast cancer cell lines were cultured in vitro and treated with the β2-AR specific agonist terbutaline (10[- 6] M and 10[- 9] M) and non-selective β-AR antagonist propranolol (10[- 5]M) to examine their effects on proliferation by cell cycle analysis, expression of pro-angiogenic (VEGF-A, VEGF-C) and signaling (p-ERK, p-CREB) molecules by ELISA, nitric oxide (NO) production by Griess assay, and miRNA expression (miR-21, miR-191) by RT-qPCR. Terbutaline elicited distinct and opposing cellular responses depending on ER status, enhancing proliferation, VEGF-C expression, miR-191 levels, and p-ERK signaling in ER-positive MCF-7 cells, while attenuating proliferation, VEGF-C expression, miR-191 levels, and p-ERK signaling in ER-negative MDA-MB-231 cells. In contrast, p-CREB signaling was enhanced in both cell lines. VEGF-A expression was downregulated in both cell lines, whereas NO production and miR-21 expression were increased in an ER-independent manner, suggesting involvement of β-adrenergic signaling mechanisms beyond direct ER mediation. Propranolol significantly attenuated terbutaline-induced effects in both cell lines, with greater magnitude of inhibition observed in ER-positive cells. These findings demonstrate that β2-AR-mediated regulation of proliferation, angiogenic signaling, and epigenetic modulators in breast cancer cells is differentially modulated by ER status, likely through selective engagement of ERK- and CREB-dependent signaling pathways. While ER-dependent crosstalk contributes to divergent outcomes, ER-independent β-adrenergic mechanisms may also play a role, underscoring the complexity of adrenergic signaling in breast cancer progression.

Terbutaline hemisulfate (THS), a selective beta-2 agonist, is preferred as a bronchodilator for the treatment of asthma and bronchitis, as well as a tocolytic agent to delay labor in acute situations during premature birth. The use of beta-2 agonists above a certain dose is considered doping in sports competitions. Therefore, it is important that they be determined with high sensitivity and selectivity within a short analysis time. In this study, a SnO2 nanoparticle-modified carbon paste electrode was developed for the determination of THS. Cyclic voltammetry and differential pulse voltammetry were employed as electrochemical methods. The operating conditions of the developed SnO2 nanoparticle-modified carbon paste electrode (SnO2NP/CPE), including the scan rate, SnO2 nanoparticle content, and pH, were optimized. At the end of the experiments, the optimum operating conditions were determined to be a scan rate of 10 mV/s, 5% SnO2 nanoparticles, and 0.25 M acetate buffer at pH 4.0. The analytical parameters of SnO2NP/CPE were also determined. The linear range of the nanosensor was 2.0-50.0 μM, with a limit of detection of 0.55 μM and a limit of quantification of 1.8 μM. In the reproducibility and repeatability tests, the coefficients of variation for 30 μM THS, based on 10 measurements, were 2.58% and 3.30%, respectively. No significant interference from NaCl, glucose, urea, and uric acid was observed in the interference experiments. In contrast, ascorbic acid, dopamine, epinephrine, and citric acid showed slight interference. Comparing the sensor response obtained on the 14th day with the initial peak current value of the nanosensor revealed no change in the nanosensor response, indicating that the developed nanosensor has good storage stability. The developed nanosensor (SnO2NP/CPE) can be prepared easily and used directly for the determination of THS in samples without additional separation or extraction steps. It is considered suitable for the determination of THS because of its advantages, including good reproducibility and reliability, low cost, and a short response time.

Head and neck cancer (HNC) is characterized by substantial immune heterogeneity and limited availability of clinically actionable molecular targets. Here, we developed an integrative single-cell eQTL-driven multi-omics framework to identify immune cell-specific causal genes and prioritize drug-repurposing candidates for HNC.

Functionalized imine-linked covalent organic polymers (COPs) have attracted tremendous attention as adsorbent. At present, most imine-linked COPs are functionalized relying on benzene groups, limiting sufficient flexibility for grafting diverse functional groups. Herein, Ugi reaction is employed to flexibly anchor carboxylic acids and isonitriles with diverse molecular structures onto the imine bonds of COP skeletons. Considering that four illegal food additives, salbutamol, ractopamine, terbutaline and ribavirin, can specifically bind with boric acid, this work selects 4-carboxyphenylboronic acid and tert‑butyl isocyanate, yielding a boronate affinity imine-linked COP. The adsorption performance of the obtained adsorbent is investigated in detail. The as-prepared adsorbent exhibits excellent selectivity, and high adsorption capacities ranging from 119.6 to 385.3 μmol/g towards four analytes. Moreover, the developed dispersive solid-phase extraction (DSPE) combined with HPLC gives low limits of detection (0.21-0.38 μg/kg) and wide linear ranges (1.2-300.0 μg/kg) for the four targets in feed samples. These results confirm the excellent adsorption properties of the adsorbent and verify the feasibility of Ugi reaction for post-synthetic functionalization of COPs.

The adrenergic system is known for its ability to influence various physiological and metabolic processes; however, its involvement in thyroid function in non-mammalian vertebrates remains poorly explored. Adult male lizards were treated with β-adrenergic agonists (isoproterenol, terbutaline, and L-isopropylamino-3-(2-thiazoloxy)-2-propanol) and the α-adrenergic antagonist (phentolamine). The effects of β-adrenergic agonists and the α-adrenergic antagonist administered as single and repeated injections were evaluated on plasma TSH, thyroid hormones, hepatic 5'-T4 ORD (type II monodeiodinase) activity, hepatic thyroid hormone contents, blood glucose levels, and thyroid gland histology. β-adrenergic stimulation produced a dose-dependent decrease in plasma TSH, accompanied by significant increases in circulating T3 and T4 levels. These changes were associated with enhanced hepatic monodeiodinase activity, increased hepatic T3 content, reduced hepatic T4 levels, and histological features indicative of thyroid activation. Repeated administrations amplified these effects. In contrast, phentolamine treatment increased plasma TSH levels but reduced circulating and hepatic T3, increased hepatic T4, and tended to decrease deiodinase activity, indicating impaired peripheral thyroid hormone activation. Histological analysis showed reduced follicular synthetic activity, although colloid resorption vacuoles were still present. IPT treatment produced no significant effects. All treatments induced hyperglycaemia, with stronger responses after repeated administrations, suggesting coordinated regulation of thyroid function and energy metabolism by adrenergic pathways. The results demonstrate that β-adrenergic signaling promotes thyroid activation and peripheral hormone conversion, whereas α-adrenergic blockade disrupts thyroid hormone homeostasis. These findings highlight a key role of adrenergic mechanisms in the neuroendocrine and metabolic regulation of reptiles, supporting their importance in physiological adaptation to environmental variability.

Aggregation of α-synuclein is intricately linked to Parkinson's disease (PD), progressing through liquid-liquid phase separation (LLPS) to toxic protofibrils and mature amyloid fibrils. Identifying compounds that selectively modulate toxic aggregation intermediates without interfering with normal cellular phase separation is a critical therapeutic goal. This study investigated the impact of terbutaline, a β2-adrenergic agonist, on the liquid-liquid phase separation, aggregation behaviour, cytotoxicity and oxidative stress induced by WT α-SYN and its variants. Terbutaline did not affect the size or physical properties of α-SYN condensates or alter fibril formation, as evidenced by unchanged Th T fluorescence and fluorescence polarization values. However, it significantly reduced the number of condensates and total aggregates, particularly amorphous moiety, in a concentration-dependent manner. This selective inhibition did not influence survival of SH-SY5Y cells but significantly reduced α-SYN-induced superoxide generation in rat RBCs-by up to 26% for WT and 53% for CT α-SYN aggregates. Distinct changes were observed in the oligomers formed by WT α-SYN and CT α-SYN. Direct interaction of terbutaline with both WT α-SYN and CT α-SYN was confirmed by isothermal titration calorimetry, with a stronger binding affinity observed for the CT α-SYN. Transmission electron microscopy showed discrete morphological changes in aggregate structure with terbutaline, supporting a shift away from toxic polymorphs. These findings highlight terbutaline's role as a potential modulator of early aggregation toxicity, warranting further exploration into structurally related compounds for therapeutic development in synucleinopathies.

Despite its established role as a cornerstone of chemotherapy for solid tumors, 5-Fluorouracil (5-FU) clinical efficacy remains limited by chemoresistance and heterogeneous drug response. Traditional explanations have focused on intracellular metabolism and genetic determinants; however, increasing evidence identifies the plasma membrane as a critical regulatory interface controlling drug availability, signaling integration, and cell fate. Here, we propose a membrane-centered framework in which compartmentalized cAMP/PKA signaling, modulated by repurposed vasoregulatory agents-levosimendan, milrinone, and terbutaline-enhances 5-FU response by functionally remodeling the cancer cell membrane. This remodeling may influence lipid raft organization, ENT1/SLC29A1 transporter trafficking, and the balance between drug influx and efflux, increasing intracellular 5-FU bioavailability and overcoming membrane-mediated pseudo-resistance. In parallel, cAMP-dependent signaling may modulate redox homeostasis, mitochondria-associated membranes, and apoptotic threshold regulation, shifting the cellular response toward irreversible cell death. Importantly, this framework is reconciled with canonical resistance mechanisms-including TYMS upregulation, DPD overexpression, and MMR deficiency-positioning membrane phenotype as a functionally upstream regulatory layer. Differential sensitivity observed experimentally in bladder versus prostate cancer models supports the concept of integrated membrane phenotype biomarkers. Clinical translation requires rigorous pharmacokinetic-pharmacodynamic validation and cardiovascular safety assessment. Redefining the plasma membrane as a dynamic therapeutic interface may provide a rationale for drug repurposing, patient stratification, and personalized combination strategies.

An innovative high-energy collision dissociation (HCD) scheme was developed using a home-built high-precision quadrupole linear ion trap tandem mass spectrometer (Q-LIT). DC-biased enhanced high-energy collision dissociation (DCBE-HCD) achieves accurate collision and efficient fragmentation of gas-phase ions on the existing platform through coordinated regulation and timing programming of the RF electric field and segmented axial DC electric field, thereby overcoming the limitation of HCD relying on a dedicated "collision cell". Based on this, an ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for four β-agonists (cimaterol, clenbuterol, terbutaline, and hydroxymethyl clenbuterol) was established. Validation results showed excellent linearity for all analytes within the range of 0.5-50 μg/kg, with correlation coefficients ≥0.999. The limits of detection and quantification were 0.005-0.030 and 0.010-0.100 μg/kg, respectively. At spiking concentrations of 1, 20, and 40 μg/kg, recoveries were 98.26-103.85%. Intraday and interday precisions were 0.57-1.10 and 1.45-2.23%, each in turn. The evaluated method was applied to the Food Analysis Performance Assessment Scheme (FAPAS) "β-Agonists in Pork Muscle Proficiency Test". The detection results of Q-LIT were highly consistent with the joint assignment results of 53 laboratories, with z scores ranging from -0.4 to 0.1, fully meeting the criterion that "|z| ≤ 2 indicates satisfactory performance". These results demonstrated that the UPLC-MS/MS method constructed by DCBE-HCD passed the rigorous assessment of FAPAS, with its accuracy, reproducibility, and applicability all reaching internationally advanced levels, thereby providing a practical example for the application of domestic mass spectrometry in food safety supervision.

Uterine contractions cause hypoxic stress to human fetuses by repeatedly occluding maternal spiral arterioles which feed the placental bed and/or compressing the loops of the umbilical cord, interrupting blood flow through the umbilical vessels. For some fetuses, even such transient and repeated interruptions of oxygenation due to ongoing uterine contractions may increase the risk of decompensation in the "high priority" central organs (i.e. heart and the brain). The onset of anaerobic metabolism and resultant production of lactate in the central organs may lead to increased likelihood of fetal neurological injury and/or perinatal death. Therefore, an immediate relaxation of the myometrium by abolishing ongoing uterine contractions may help to rapidly restore oxygenation to fetal central organs. Such timely administration of acute tocolytics would help maintain aerobic metabolism in the high-priority fetal central organs, avoiding the onset of neurological injury and/or perinatal death. Commonly used acute tocolytics include beta-sympathomimetics, nitric oxide donors, oxytocin antagonists, which have different mechanisms of actions, and maternal side-effect profile. The indications include elimination of uterotonic-induced excessive uterine contractions to facilitate normalization of the fetal heart rate so as to allow continuation of labor in anticipation of vaginal birth and for rapidly improving the fetal condition immediately prior to an emergency cesarean section. The latter includes umbilical cord prolapse or chronic hypoxia when a delay in birth is anticipated. This review addresses the indications for acute tocolytics (why), the recommended timing of administration (when), ideal tocolytic (what), route of administration (how), side effects and contraindications (why-not). Based on current evidence, and pharmacokinetics, 250 mcg of subcutaneous terbutaline (or another beta-sympathomimetic such as intravenous fenoterol) is the recommended first line tocolytic, unless there are specific maternal contraindications. In the absence of maternal hypotension, 100 mg of intravenous glyceryl trinitrate (GTN) may be administered as an alternative. Acute tocolytics are not recommended to treat myometrial irritability observed in chorioamnionitis or in acute feto-maternal hemorrhage.