salbutamol (Inspiryl Turbuhaler)

Contemporary bulk-fill restorative materials under simulated asthma inhalation therapy: a comparative assessment of surface stability.

Misilli Tuğba T, Yenidünya Özge Gizem ÖG, Çelik Enes E

To compare the surface stability of four contemporary bulk-fill restorative materials following simulated 21-day antiasthmatic inhalation therapy, and to investigate the relationships among the resulting surface changes. One hundred ninety-two disc-shaped specimens (8 × 2 mm) were prepared from four bulk-fill restorative materials: a nanofilled composite (Filtek One Bulk), an alkasite (Cention Forte), a giomer (Beautifil-Bulk) and a self-cure composite (Stela Capsule) (n = 8 per subgroup). Specimens were exposed once daily for 21 days via nebulizer to budesonide, fluticasone, salbutamol, budesonide + salbutamol, or fluticasone + salbutamol, while the control specimens were stored in artificial saliva. Changes in color (ΔE00), gloss, microhardness and surface roughness were assessed relative to baseline. Data were analyzed using two-way ANOVA or Kruskal-Wallis tests and Spearman correlations (α = 0.05). Restorative material and inhaler group significantly affected all four parameters (p < 0.05). Salbutamol caused significantly greater changes than budesonide, fluticasone and the control in every material; the combination regimens were intermediate, and budesonide and fluticasone generally did not differ. The self-cure composite was the least stable and the nanofilled composite the most stable (except for color); microhardness loss increased significantly in the order Filtek One Bulk < Beautifil-Bulk < Cention Forte < Stela Capsule. All four surface parameters were strongly and positively correlated (ρ = 0.79-0.94; p < 0.001). Simulated antiasthmatic inhaler exposure degraded the surface of all bulk-fill materials in a material-dependent manner, with salbutamol exerting the greatest effect. The nanofilled composite showed the highest resistance. For asthmatic patients, and especially frequent salbutamol users, a highly filled light-cured nanofilled composite appears preferable to a self-cure bulk-fill composite where surface durability is clinically important.

Native Mass Spectrometry Reveals Ligand-Specific Conformational Heterogeneity of the β1-Adrenergic Receptor Using Nanobody Probes.

Wang Yi-Quan YQ, Lian Guan-Ting GT, Chen Yi-An YA, Chen Rong R et al.

G protein-coupled receptors (GPCRs) are central physiological signal transducers and represent a primary class of therapeutic targets. While emerging evidence highlights a critical link between ligand-induced receptor conformations and pharmacological outcomes, the structural diversity dictating GPCR-G protein interface interactions remains incompletely understood. High-resolution structural studies reveal discrete, ligand-stabilized states, but these static snapshots do not fully capture the dynamic processes underlying GPCR activation and ligand efficacy. To address this, we established a native mass spectrometry (nMS) platform to probe ligand-induced conformational heterogeneity at the GPCR intracellular interface. Using the β1-adrenergic receptor (β1AR) as a model, we demonstrated a strong correlation between ligand efficacy and receptor complex formation with diverse active-state-specific nanobodies. Notably, leveraging the quantitative capacity of nMS, we uncovered distinct propensities of two highly similar nanobodies, Nb80 and Nb6B9, and showed that Nb6B9 engages weak-agonist-stabilized receptor states more effectively than Nb80. These interactions indicate that Nb6B9 recognizes ligand-specific conformations distinct from active states induced by full agonists. To gain structural insights, we utilized Nb6B9 chimeras with exchanged complementarity-determining regions (CDRs) and identified CDR1 and CDR3 as the primary drivers for ligand-specific recognition, implicating the involvement of receptor transmembrane motifs TM5 and TM6 in this conformational diversity. Finally, we demonstrated that nanobody-based nMS can distinguish receptor responses induced by the two salbutamol enantiomers, implying stereochemistry-dependent intracellular interface heterogeneity. Together, our study highlights the utility of nanobody-based nMS for evaluating the structural heterogeneity and dynamic landscapes of GPCRs.

Nebulized Magnesium Sulfate as an Adjunct to Standard Therapy in Infants with Acute Bronchiolitis: A Double Blind Randomized Controlled Trial.

Karimian Pegah P, Dehghani Mohammadabadi Fahimeh F, Charmduzi Forugh F, Khoshnezhad Ebrahimi Hamidreza H et al.

The evidence regarding the efficacy of magnesium sulfate (MgSO₄) in bronchiolitis is conflicting, and high-quality trials involving very young infants are limited. To compare the efficacy of nebulized magnesium sulfate, salbutamol, and 3% hypertonic saline against nebulized salbutamol and 3% hypertonic saline in infants aged 1-6 months who are admitted with a first episode of mild-to-moderate bronchiolitis. The primary outcomes were physiological parameters including oxygen saturation (SpO₂), respiratory rate (RR), and pulse rate (PR). Length of hospital stay (LOS), and Respiratory Distress Assessment Instrument (RDAI) score were evaluated as exploratory outcomes, along with escalation of care and adverse events. In this parallel, double-blind randomized controlled trial conducted from August 2022 to February 2023, 62 eligible infants were allocated (1:1) to receive three consecutive 20-minute nebulizations of salbutamol, MgSO₄, and 3% saline (intervention) or salbutamol and 3% saline (control), followed by identical doses every 6 hours for up to 72 hours. All caregivers, clinicians, and outcome assessors were blinded. Outcome assessments were performed at baseline (pre-intervention), 1 hour after the initial dose, and every 24 hours thereafter (± 2 hours) until discharge or 72 hours, whichever occurred first. LOS was defined as the duration (in hours) from randomization until predefined discharge criteria were met (SpO₂ ≥ 94% in room air for ≥ 12 hours, adequate oral intake, respiratory rate within age norms, RDAI ≤ 3). Among the 62 infants, 33 (53.2%) received triple-drug therapy, while 29 (46.8%) received standard dual therapy. The baseline characteristics were comparable, with a mean age as 3.6 ± 1.25 months and 56.5% male. The median Length of stay (LOS) was shorter in the MgSO₄ group (6.0 days, IQR 5-7) compared to the control group (7.0 days, IQR 6-9; P = 0.046, Mann-Whitney U). No significant differences were observed between groups for daily RDAI, RR, PR, or SpO₂ (repeated-measures ANOVA, P > 0.05). None of the infants required intensive care, mechanical ventilation, or experienced serious drug-related events. This double-blind randomized trial did not demonstrate a statistically significant effect on its prospectively registered primary outcomes (oxygen saturation, respiratory rate, heart rate). The observed difference in length of hospital stay (a secondary, unregistered outcome; median 6.0 vs. 7.0 days; unadjusted P = 0.046) did not reach statistical significance after Bonferroni correction for multiple comparisons (corrected threshold: P < 0.01) and should be regarded as exploratory and hypothesis-generating only. This trial should be interpreted as null and inconclusive. Adequately powered, prospectively registered confirmatory trials are necessary before any clinical recommendations can be made.

South Africa shifts away from salbutamol-only asthma relief.

Adepoju Paul P