Publications by authors named "B Svobodova"
The current pharmacological pretreatment and medical treatment of nerve agent poisoning is an insufficiently addressed medical task. The prophylactic efficacy of a novel compound acting dually as an acetylcholinesterase inhibitor and NMDA receptor antagonist (K1959) and the therapeutic efficacy of a novel NMDA receptor antagonist (K2060) were evaluated in the NMRI mice model of nerve agent poisoning by tabun, soman and sarin. Their added value to the standard antidotal treatment (a combination of oxime reactivator and atropine) was also analyzed.
View Article and Find Full Text PDFA novel patient group with chronic pulmonary fibrosis is emerging post COVID-19. To identify patients at risk of developing post-COVID-19 lung fibrosis, we here aimed to identify systemic proteins that overlap with fibrotic markers identified in patients with idiopathic pulmonary fibrosis (IPF) and may predict COVID-19-induced lung fibrosis. Ninety-two proteins were measured in plasma samples from hospitalized patients with moderate and severe COVID-19 in Sweden, before the introduction of the vaccination program, as well as from healthy individuals.
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- Tacrine (THA) has been phased out due to safety concerns but is still used as a framework in drug development for its effectiveness against multiple targets, although its potential for liver toxicity is a major concern.
- Researchers developed 30 new derivatives focusing on minimizing hepatotoxicity while maintaining anticholinesterase properties and targeting specific NMDA receptor subtypes, leading to the identification of two promising candidates, I-52 and II-52.
- Compound I-52 was highlighted as a lead candidate, demonstrating minimal toxicity, favorable neuroprotective effects in behavioral tests, and lower hepatotoxicity compared to traditional THA-based drugs.
Article Synopsis
- - Tacrine, an Alzheimer's drug, was withdrawn in 2013 due to liver toxicity linked to its metabolite, 7-OH-tacrine, which interacts with liver proteins.
- - The study evaluated various animal and human models to understand tacrine's metabolism and found that while animal models weren't fully accurate, 3D cultures of primary human hepatocytes were the best for simulating human reactions.
- - Interestingly, 7-OH-tacrine turned out to be the least toxic variant, challenging previous assumptions about its harmful effects and suggesting potential for safer tacrine derivatives through chemical modifications.
Alzheimer's disease (AD) is a complex disease with an unknown etiology. Available treatments, limited to cholinesterase inhibitors and -methyl-d-aspartate receptor (NMDAR) antagonists, provide symptomatic relief only. As single-target therapies have not proven effective, rational specific-targeted combination into a single molecule represents a more promising approach for treating AD, and is expected to yield greater benefits in alleviating symptoms and slowing disease progression.
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