Nalazite se na CroRIS probnoj okolini. Ovdje evidentirani podaci neće biti pohranjeni u Informacijskom sustavu znanosti RH. Ako je ovo greška, CroRIS produkcijskoj okolini moguće je pristupi putem poveznice www.croris.hr
izvor podataka: crosbi

Novel (bio)molecules for new organophosphate intoxication treatments (CROSBI ID 614701)

Prilog sa skupa u zborniku | sažetak izlaganja sa skupa | domaća recenzija

Radić, Zoran ; Sit, Rakesh K. ; Žunec, Suzana ; Maček Hrvat, Nikolina ; Kovarik, Zrinka ; Fokin, Valery V. ; Taylor, Palmer Novel (bio)molecules for new organophosphate intoxication treatments // Book of Abstracts of the Congress of the Croatian Society of Biochemistry and Molecular Biology "The Interplay of Biomolecules", HDBMB 2014 / Katalinić, M. ; Kovarik, Z. (ur.). Zagreb: The Croatian Society of Biochemistry and Molecular Biology, 2014. str. 46-x

Podaci o odgovornosti

Radić, Zoran ; Sit, Rakesh K. ; Žunec, Suzana ; Maček Hrvat, Nikolina ; Kovarik, Zrinka ; Fokin, Valery V. ; Taylor, Palmer

engleski

Novel (bio)molecules for new organophosphate intoxication treatments

Persistent occurrence of potentially fatal human intoxications by pesticide and nerve agent organophosphates (OPs) is at present insufficiently counteracted by combined intramuscularly (i.m.) or intravenously (i.v.) administered therapy of atropine with nucleophilic pyridinium aldoxime acetylcholinesterase (AChE) reactivators. Therapeutic efficacy of pralidoxime (2PAM), obidoxime, and HI-6, the most commonly used reactivator aldoximes, is low in cases of massive OP pesticide or nerve agent exposure due to constant AChE reinhibition by the excess circulating OP. Those oximes do not penetrate Blood Brain Barrier, because of their charge, and can not reactivate OP-inhibited brain AChE. Finally, their bioavailability is generally low, and clearance is rapid, restricting useful administration modes to i.m. or i.v, inconvenient for rapid treatment of larger number of exposed individuals and populations. Owing to discovery and structure-activity refinements of several novel biologically active molecules, we were able, in recent years, to develop several alternative and complementary therapeutic approaches to treatment of OP intoxication. Our uncharged acetamide oxime RS194B shows low intrinsic toxicity, BBB penetration, and high bioavailability and efficacy upon oral administration. Our imidazole aldoxime RS2-33A efficiently reactivates intrinsic, tissue butyrylcholinesterase inhibited by OPs promoting in situ hydrolytic breakdown and removal of offending OPs in the exposed tissue. Finally, combined administration of our aging resistant AChE mutant with suitable novel oxime reactivator provides a useful means of hydrolytic clearing of fast aging nerve agent Soman from the exposed circulation. This research was supported by the CounterACT Program, National Institutes of Health Office of the Director (NIH OD), and the National Institute of Neurological Disorders and Stroke (NINDS), Grant Numbers U01 NS058046, R21NS072086 and R21NS084904.

alternative and complementary therapeutic approaches; oxime; RS194B; BBB penetration; bioavailability; RS2-33A

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

nije evidentirano

Podaci o prilogu

46-x.

2014.

objavljeno

Podaci o matičnoj publikaciji

Book of Abstracts of the Congress of the Croatian Society of Biochemistry and Molecular Biology "The Interplay of Biomolecules", HDBMB 2014

Katalinić, M. ; Kovarik, Z.

Zagreb: The Croatian Society of Biochemistry and Molecular Biology

978-953-95551-5-1

Podaci o skupu

The Congress of the Croatian Society of Biochemistry and Molecular Biology "The Interplay of Biomolecules", HDBMB 2014

pozvano predavanje

24.09.2014-27.09.2014

Zadar, Hrvatska

Povezanost rada

Kemija