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BoNT/Action beyond neurons.
Toxicon
January 2025
National Research Council of Italy, Institute of Biochemistry and Cell Biology, 00015, Monterotondo, RM, Italy. Electronic address:
Botulinum neurotoxin type A (BoNT/A) has expanded its therapeutic uses beyond neuromuscular disorders to include treatments for various pain syndromes and neurological conditions. Originally recognized for blocking acetylcholine release at neuromuscular junctions, BoNT/A's effects extend to both peripheral and central nervous systems. Its ability to undergo retrograde transport allows BoNT/A to modulate synaptic transmission and reduce pain centrally, influencing neurotransmitter systems beyond muscle control.
View Article and Find Full Text PDFSafety and efficacy of satralizumab in patients with generalised myasthenia gravis (LUMINESCE): a randomised, double-blind, multicentre, placebo-controlled phase 3 trial.
Lancet Neurol
February 2025
Department of Neurology, International University of Health and Welfare, Narita, Japan.
Background: Evidence from preclinical studies suggests that IL-6 signalling has the potential to modulate immunopathogenic mechanisms upstream of autoantibody effector mechanisms in patients with generalised myasthenia gravis. We aimed to assess the safety and efficacy of satralizumab, a humanised monoclonal antibody targeting the IL-6 receptor, in patients with generalised myasthenia gravis.
Methods: LUMINESCE was a randomised, double-blind, placebo-controlled, multicentre, phase 3 study at 105 sites, including hospitals and clinics, globally.
Comparison of the Effects of Sugammadex Recommended Dose (2 mg/kg) and Fixed Dose of 200 mg on the Reversal of Moderate Neuromuscular Block and Recovery Profile in Adult Patients.
Medicina (Kaunas)
January 2025
Department of Anaesthesiology and Pain Medicine, Konyang University Hospital, Konyang University Myunggok Medical Research Institute, Konyang University College of Medicine, Daejeon 35365, Republic of Korea.
: Neuromuscular blocking agents are essential to ensure optimal surgical conditions during general anesthesia. Sugammadex, a selective binding agent, is widely used to reverse neuromuscular blockade. While weight-based dosing (2 mg/kg for moderate blockade) is recommended, many clinicians administer a fixed dose of 200 mg in clinical practice, potentially leading to overdosing.
View Article and Find Full Text PDFQnox index for quantification of intraoperative nociception and analgesia: a prospective single-centre validation study.
Br J Anaesth
January 2025
Department of Anaesthesiology, Peking University First Hospital, Beijing, China; Outcomes Research Consortium, Cleveland, OH, USA.
Background: The Qnox index is a novel monitor to quantify intraoperative nociception based on an electroencephalographic algorithm. We evaluated the ability of the Qnox index to discriminate noxious from non-noxious stimuli, respond to stimuli, and discriminate different levels of analgesia in patients under propofol anaesthesia with neuromuscular block.
Methods: Qnox was compared with heart rate and mean arterial pressure with five designated stimuli: tetanic stimulations without (tetanic 1) and with sufentanil (tetanic 2), skin incision, tracheal intubation, and a non-noxious period.
Discovery of an Ultralong-acting Nondepolarizing Neuromuscular Blocker That Displays Short Onset Time and On-Demand Rapid Reversal by a Biocompatible Antagonist.
J Med Chem
January 2025
Department of Chemistry, Fudan University, 2205 Songhu Road, Shanghai 200438, China.
The combination of ultralong-acting neuromuscular block and subsequent on-demand rapid reversal may provide prolonged surgeries with improved conditions by omitting continuous or repetitive blocker administration, enabling a more stable and predictable hemodynamic profile and eliminating residual block. For this target, we prepared 19 imidazolium-incorporated tetracationic macrocycles. In vivo studies with rats revealed that one macrocycle (IMC-14) displays extremely high blocking activity.
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