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Dantrolene is an HDL-associated paraoxonase-1 activator with immunosuppressive and atheroprotective properties.
Biochim Biophys Acta Mol Cell Biol Lipids
January 2025
Institute of Biosciences and Applications, National Center for Scientific Research "Demokritos", Agia Paraskevi, Athens, Greece. Electronic address:
Human paraoxonase 1 (PON1), an enzyme bound to high-density lipoprotein (HDL), hydrolyzes oxidized lipids and contributes to HDL atheroprotective functions. Decreased serum paraoxonase and arylesterase activities of PON1 have been reported in patients at increased atherosclerosis risk, such as rheumatoid arthritis patients, and associated with arthritis severity and cardiovascular risk. Agents that can modulate PON1 activity and HDL-mediated effects have not been discovered.
View Article and Find Full Text PDFEco-sustainable chromatographic method for the determination of favipiravir and nitazoxanide for COVID-19: application to human plasma.
BMC Chem
January 2025
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Nile Valley University (NVU), El Fayoum, 63518, Egypt.
Coronavirus disease 2019 (COVID-19), an extremely contagious illness, has posed enormous challenges to healthcare systems around the world. Although the evidence on COVID-19 management is growing, antiviral medication is still the first line of treatment. Therefore, it is critical that effective, safe, and tolerable antivirals be available to treat early COVID-19 and stop its progression.
View Article and Find Full Text PDFDantrolene inhibition of ryanodine receptor 1 carrying the severe malignant hyperthermia mutation Y522S visualized by cryo-EM.
Structure
December 2024
Department of Physiology and Biophysics, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA. Electronic address:
Mutations in the skeletal isoform of the ryanodine receptor 1 (RyR1) pose grave risks during anesthesia or treatment with succinylcholine muscle relaxants. These can trigger a potentially lethal malignant hyperthermia (MH) episode via intracellular calcium increase mainly from RyR1 channel leakage. Dantrolene is the only known treatment option to prevent death.
View Article and Find Full Text PDFAn hiPSC-CM approach for electrophysiological phenotyping of a patient-specific case of short-coupled TdP.
Stem Cell Res Ther
December 2024
Department of Medical Physiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Introduction: A healthy young woman, age 26 without prior cardiac complications, experienced an out-of-hospital cardiac arrest caused by ventricular fibrillation (VF), which coincided with a fever. Comprehensive diagnostics including echo, CMR, exercise testing, and genetic sequencing, did not identify any potential cause. This led to the diagnosis of idiopathic VF and installment of an implantable cardioverter defibrillator, which six months later appropriately intervened another VF episode under conditions comparable to the first event.
View Article and Find Full Text PDFDiagnostic Challenges in Malignant Hyperthermia and Anesthesia-Induced Rhabdomyolysis: A Case Study.
Am J Case Rep
December 2024
Department of Surgery, Medical University of Sofia, University Hospital "Queen Giovanna - ISUL", Sofia, Bulgaria.
BACKGROUND Malignant hyperthermia (MH) and anesthesia-induced rhabdomyolysis (AIR) are rare, yet life-threatening complications that need prompt therapeutic actions and logistic preparedness for treatment success. Both conditions are triggered by general anesthetics, particularly volatiles and depolarizing muscle relaxants. In comparison with MH, which is an inherited pharmacogenomic disease of calcium channel receptor subpopulation and arises only after trigger exposure, AIR has been described mostly in patients with muscular dystrophies.
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