Objective: To investigate the effects of continuous pyridostigmine infusion on immobilization-induced muscle weakness. Critical illness often results in immobilization of limb and respiratory muscles, leading to muscle atrophy and up-regulation of nicotinic acetylcholine receptors. Pyridostigmine reversibly blocks acetylcholinesterase and has the potential to improve neuromuscular transmission and decrease acetylcholine receptor number.
Design: Prospective, randomized, controlled experimental study.
Setting: Animal laboratory, university hospital.
Subjects: Male Sprague-Dawley rats.
Interventions: A total of 40 rats were immobilized in one hind limb by pinning knee and ankle joints. Rats received either continuous pyridostigmine (15 mg.kg.day) or saline subcutaneously via implanted osmotic pumps.
Measurements And Main Results: After 7 days and 14 days of immobilization, neuromuscular function, atracurium pharmacodynamics, and expression of acetylcholine receptors were evaluated. At 7 days and 14 days after immobilization, muscle force decreased in all untreated groups, whereas effective doses for paralysis with atracurium and acetylcholine receptor number in the tibialis were significantly increased. Pyridostigmine-treated rats showed a significantly improved muscle force and muscle mass in the immobilized limb. This was associated with an attenuation of acetylcholine receptor up-regulation in the respective leg. At this time, the dose-response curve for atracurium on the immobilized side was shifted to the left in the pyridostigmine group. After 14 days, muscle tension was still less depressed with pyridostigmine infusion, and resistance to the effects of atracurium was still attenuated. However, there were no differences in acetylcholine receptor expression between the immobilized sides of both groups.
Conclusions: Continuous pyridostigmine infusion improves muscle weakness after 7 days and 14 days of immobilization. The up-regulation of acetylcholine receptors and the concomitant resistance to atracurium is attenuated in animals treated with pyridostigmine after 7 days of immobilization.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1097/CCM.0b013e3181c31297 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Microfluidic Cultures of Basal Forebrain Cholinergic Neurons for Assessing Retrograde Cell Death by Live Imaging.
Bio Protoc
January 2025
Department of Biological Sciences, Rutgers University, Newark, NJ, USA.
Neurons are highly polarized cells, with axons that may innervate distant target regions. In the brain, basal forebrain cholinergic neurons (BFCNs) possess extensive axons that project to several target regions such as the cortex, hippocampus, and amygdala, and may be exposed to a specific microenvironment in their axon targets that may have retrograde effects on neuronal health. Interestingly, BFCNs express the pan-neurotrophin receptor p75NTR throughout life while also concomitantly co-expressing all Trk receptors, making them capable of responding to both mature and precursor neurotrophins to promote survival or apoptosis, respectively.
View Article and Find Full Text PDFThe stoichiometry of the α4β2 neuronal nicotinic acetylcholine receptors determines the pharmacological properties of the neonicotinoids, and recently introduced butenolide and sulfoximine.
Neurotoxicology
January 2025
Laboratoire Physiologie, Ecologie and Environnement (P2E), Université d'Orléans, UR 1207, USC-INRAE 1328, 1 rue de Chartres, 45067 Orléans, France; Institut Universitaire de France (IUF), 1 rue Descartes 75005 Paris, France. Electronic address:
Although neonicotinoids were considered safe for mammals for many decades, recent research has proven that these insecticides can alter cholinergic functions by interacting with neuronal nicotinic acetylcholine (ACh) receptors (nAChRs). One such receptor is the heteromeric α4β2 nAChR, which exists under two different stoichiometries: high sensitivity and low sensitivity α4β2 nAChRs. To replace these insecticides, new classes of insecticides have been developed, such as, sulfoximine, sulfoxaflor, and the butanolide, flupyradifurone.
View Article and Find Full Text PDFSeasonal variation in myasthenia gravis incidence.
J Neuroimmunol
January 2025
Neurology Unit, University Hospital of Sassari, Sassari, Italy. Electronic address:
Introduction: Environmental factors may contribute to myasthenia gravis (MG) development, sometimes with seasonal patterns of exposure. However, whether seasonality has an impact on MG incidence remains unclear. We aimed to investigate the association between seasonality and MG onset.
View Article and Find Full Text PDFNegative Symptoms in Schizophrenia: An Update on Research Assessment and the Current and Upcoming Treatment Landscape.
CNS Drugs
January 2025
New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY, 10032, USA.
Article Synopsis
- The negative symptoms of schizophrenia, like lack of emotion and motivation, are hard to treat and significantly impact daily functioning.
- This review highlights current research on treatment options for these symptoms, categorizing them into different types and evaluating various assessment scales.
- Although no treatments are conclusively proven as the best for these symptoms, some off-label and investigational medications show promise, including cariprazine and memantine, and further research is needed to explore new therapeutic possibilities.
Efgartigimod efficacy and safety in refractory myasthenia gravis: UK's first real-world experience.
J Neurol Neurosurg Psychiatry
January 2025
Department for Neuromuscular Disease, National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
Background: We report our experience of patients with generalised myasthenia gravis (gMG) treated with efgartigimod, an neonatal Fc receptor antagonist, under the Early Access to Medicine Scheme (EAMS) in the UK.
Methods: Data from all UK patients treated with efgartigimod under the EAMS July 2022 to July 2023 were collected retrospectively. Efgartigimod was administered as per the ADAPT protocol (consisting of a treatment cycle of four infusions at weekly intervals with further cycles given according to clinical need).
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!