Toxicology - Prof. RNDr. Jiří Patočka, DrSc

Biomedical aspects of chiral molecules
Popis: This article defines some of the terms used in chiral chemistry and some of the basic mechanistic issues that arise in stereochemistry in pharmacology. Attention is also drawn to the impact of stereochemistry on drug regulation and its significance for new drug development. The stereoselectivity of drugs is underpinned by the fact that the human body is essentially a chiral structure. The rationale for development of chiral drugs is the suggestion that single stereoisomer drugs would provide superior therapy by allowing reductions in dosage, reduced variability in metabolism and response, simpler dose-response relationships and improved tolerability.
Přidáno dne: 18.07. 2005 Kliknutí: 1794
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How does lithium mediate its therapeutic effects?
Popis: For the psychiatrist, lithium is an effective drug for both the treatment and prophylaxis of bipolar disorder. The molecular mechanisms underlying its therapeutic actions have not yet been fully explained. The effects of lithium on a number of enzymes and biological processes have been studied. Inositol monophosphatase and glycogen synthase kinase-3 (GSK-3) have been suggested as the relevant intracellular targets for lithium action. The discovery of the role of GSK-3, the Wnt signalling system, and the anti-apoptotic factor Bcl-2 has led to the suggestion that there could be a therapeutic use for lithium in neurodegenerative disorders, such as Alzheimer´s disease
Přidáno dne: 18.07. 2005 Kliknutí: 1708
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Inhibitory acetylcholinesterasy - od nervových plynů k léčivům Alzheimerovy choroby
Popis: Nervové plyny typu sarinu či somanu jsou silnými inhibitoty acetylcholinesterázy. Tento enzym je ale také cílovou biomakromolekulou mnoha léčiv používaných ke zmírnění kognitivního deficitu u Alzheimerovy choroby.
Přidáno dne: 23.05. 2006 Kliknutí: 1715 Hodnocení: 1 (Účastníků: 1)
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Inhibitory mikrotubulů
Popis: The review deals with current knowledge of microtubule inhibitors from different natural sources, which are a very variegated group of compounds with a strong effect on cytoskeletal functions. Their use is one of the most frequen therapeutic strategies in carcinoma treatment. Drugs like taxol or vinblastine are widely used, although they have some drawbacks. The discovery of new compounds, such as epothilones, halichondrins, lamellarins, didemnins, could overcome some of the problems occurring in application of the earlier drugs. In addition, these natural compounds are used as an outstanding scientific tool in physiological and biochemical experiments, serving as model structures for synthesis of new compounds with expected effects and better pharmacological properties, such as synthetic taxanes docetaxel, vindesin or vinorelbin.
Přidáno dne: 18.07. 2005 Kliknutí: 1606
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Oxime reactivation of acetylcholinesterase inhibited by toxic phosporus ester: In vitro kinetics and
Popis: Owing to the threat of organophosphate exposures, not only to pesticides but also to nerve agents, it is very important to know the whole process of organophosphates-inhibited acetylcholinesterase (AChE, EC 3.1.1.7) reactivation. Although current antidotes against organophosphorus intoxications consist also of prophylactics, AChE reactivators are still needed especially in the case of intoxications with high doses of organophosphates, for which prophylactic treatment is not effective. For this reason, new AChE reactivators are still being developed. Our work summarizes accurately the whole reactivation process, and offers some help for scientists who are interested in the area of AChE reactivation.
Přidáno dne: 18.07. 2005 Kliknutí: 1606
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Reactivation of organophosphate inhibited acetylcholinesterase
Popis: The relationship between the ability to reactivate acetylcholinesterase inhibited by organophosphorus compounds and the length of linking chain between two 4-hydroxyiminomethylpyridinium rings of acetylcholinesterase reactivators. a,w-bis(4-hydroxyiminomethylpyridinium) alkanes have been used as the tested acetylcholinesterase reactivators. These oximes differ in the number of methylene groups on the connecting chain. A three or four membered linking chain seems to be the ideal length for the satisfactory reactivation potency with the exception of reactivators of cyclosarin-inhibited acetylcholinesterase. In this case, the most efficacious acetylcholinesterase reactivator has one methylene group on the connecting chain.
Přidáno dne: 18.07. 2005 Kliknutí: 1716
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VLIV DÉLKY A TVARU SPOJOVACÍHO RETEZCE BISKVARTERNÍCH REAKTIVÁTORU
Popis: Antidotní prípravky urcené pro lécbu intoxikací nervove paralytickými látkami se skládají z anticholinergik (atropin) a reaktivátoru acetylcholinesterázy (AChE) (pralidoxim, obidoxim, methoxim nebo látka HI-6). Vzhledem k tomu, že v soucasnosti neexistuje univerzální reaktivátor schopný reaktivovat AChE inhibovanou všemi potenciálními nervove paralytickými látkami, vývoj nových úcinnejších reaktivátoru stále pokracuje. Za tímto úcelem je nutné znát, jak jednotlivé strukturní faktory reaktivátoru ovlivnují jejich reaktivacní schopnost. Mezi nejvíce diskutované faktory patrí prítomnost a pocet oximových skupin, prítomnost a pocet kvarterních dusíku, délka a tvar spojovacího retezce. V této práci bylo in vitro testováno jedenáct reaktivátoru AChE lišících se délkou a tvarem spojovacího retezce. Jako vhodný zástupce nervove paralytických látek byl použit sarin. Z výsledku vyplývá, že nejvyšší reaktivacní schopnosti bylo dosaženo u trimedoximu (54 %) a oximu K074 (54 %). Této reaktivacní schopnosti však bylo dosaženo v koncentracích nedosažitelných u cloveka v prubehu antidotní terapie (10-3 M). V terapeuticky relevantních koncentracích (10-5 M) se jevily jako nadejné oximy TO 047 (20 %) a TO 033 (28 %).
Přidáno dne: 08.08. 2006 Kliknutí: 1640
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