Subetadex-α-methyl (SBX-Me), a modified, polyanionic cyclodextrin scaffold, has been evaluated for its utilization as a medical countermeasure (MCM) to neutralize the effects of fentanyl and related opioids. Initial toxicity assays demonstrate that SBX-Me has a nontoxic profile, comparable to the FDA-approved cyclodextrin-based drug Sugammadex. Pharmacokinetic analysis showed rapid clearance of SBX-Me with an elimination half-life of ∼7.
View Article and Find Full Text PDFTher Adv Musculoskelet Dis
July 2023
Background: Patients with idiopathic inflammatory myopathies (IIMs) are at risk of reduced bone mineral density (BMD).
Objectives: To compare the prevalence of reduced BMD between patients with IIMs and controls and to determine its risk factors.
Design: This was a single-center case-control study.
Transgenerational epigenetic inheritance (TEI) allows the transmission of information through the germline without changing the genome sequence, through factors such as non-coding RNAs and chromatin modifications. The phenomenon of RNA interference (RNAi) inheritance in the nematode Caenorhabditis elegans is an effective model to investigate TEI that takes advantage of this model organism's short life cycle, self-propagation, and transparency. In RNAi inheritance, exposure of animals to RNAi leads to gene silencing and altered chromatin signatures at the target locus that persist for multiple generations in the absence of the initial trigger.
View Article and Find Full Text PDFA patient-reported history of penicillin allergy is a common label with a prevalence of about 10%. However, as many as 95% of patients reporting a penicillin allergy do not have a true immunoglobin-E (IgE)-mediated allergic reaction. Unfortunately, penicillin allergy mislabeling is problematic, leading to inappropriate antibiotic use and negative consequences, such as adverse drug events, suboptimal outcomes, and increased costs.
View Article and Find Full Text PDFThe ability of the cyclodextrin-oxime construct 6-OxP-CD to bind and degrade the nerve agents Cyclosarin (GF), Soman (GD) and S-[2-[Di(propan-2-yl)amino]ethyl] O-ethyl methylphosphonothioate (VX) has been studied using 31P-nuclear magnetic resonance (NMR) under physiological conditions. While 6-OxP-CD was found to degrade GF instantaneously under these conditions, it was found to form an inclusion complex with GD and significantly improve its degradation (t1/2 ~ 2 hrs) relative over background (t1/2 ~ 22 hrs). Consequently, effective formation of the 6-OxP-CD:GD inclusion complex results in the immediate neutralization of GD and thus preventing it from inhibiting its biological target.
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