Acetylcholinesterase reactivators (oximes) are compounds used for antidotal treatment in case of organophosphorus poisoning. The dissociation constants (pK(a1)) of ten standard or promising acetylcholinesterase reactivators were determined by ultraviolet absorption spectrometry. Two methods of spectra measurement (UV-vis spectrometry, FIA/UV-vis) were applied and compared. The soft and hard models for calculation of pK(a1) values were performed. The pK(a1) values were recommended in the range 7.00-8.35, where at least 10% of oximate anion is available for organophosphate reactivation. All tested oximes were found to have pK(a1) in this range. The FIA/UV-vis method provided rapid sample throughput, low sample consumption, high sensitivity and precision compared to standard UV-vis method. The hard calculation model was proposed as more accurate for pK(a1) calculation.
- MeSH
- acetylcholinesterasa analýza chemie MeSH
- chemie farmaceutická metody normy MeSH
- oximy analýza chemie MeSH
- reaktivátory cholinesterázy analýza chemie MeSH
- spektrofotometrie ultrafialová metody normy MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- validační studie MeSH
Poisoning from chemical warfare agents (CWAs) such as sarin is associated with neuronal degeneration. This damage is thought to result from glutamatergic excitotoxicity such as seen following kainic acid induced seizures. In order to search for novel neuroprotectants it is necessary to select good mouse models for susceptibility to nerve agent-induced seizures and the resulting neurodegeneration. The mouse strains tested (C57BL/6, ICR, DBA/2, SW, and FVB/N, Harlan Laboratory) had widely different sensitivity to sarin as shown by differences in the dose required resulting in 50% mortality, LD50. Differences also were observed among the strains in Fluoro-Jade C staining with the C57BL/6 and DBA having little to no staining when euthanized at 7 days whereas the other strains did. Differences in acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activity were found among the strains as well. The ICR strain was excluded from the FOB and weight data due to difficulty getting a consistent LD50. Weight loss and FOB scores were similar for all strains. All strains had inhibited AChE activity after sarin exposure and exhibited inhibition of CNS BuChE after sarin exposure but only ICR and SW reached significance.
- MeSH
- acetylcholinesterasa analýza krev MeSH
- butyrylcholinesterasa analýza krev MeSH
- chemické bojové látky otrava MeSH
- cholinesterasové inhibitory aplikace a dávkování otrava MeSH
- chování zvířat účinky léků MeSH
- degenerace nervu * chemicky indukované patologie MeSH
- druhová specificita MeSH
- hmotnostní úbytek účinky léků MeSH
- inbrední kmeny myší * MeSH
- LD50 MeSH
- myši inbrední C57BL MeSH
- myši inbrední DBA MeSH
- myši inbrední ICR MeSH
- myši MeSH
- neurony patologie účinky léků MeSH
- otrava organofosfáty MeSH
- pohybová aktivita účinky léků MeSH
- sarin * aplikace a dávkování otrava MeSH
- tělesná hmotnost účinky léků MeSH
- záchvaty chemicky indukované patologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
- srovnávací studie MeSH
Flow injection analysis (FIA) is an analytical method where the reaction mixture is injected into flow of liquid. The reaction product is monitored by a suitable detector such as ultraviolet/visible (UV/VIS) spectrophotometric or electrochemical detector. Mass spectrometric detectors (MS) are coming to be a standard equipment of analytical laboratories in the present time. This work is focused on application of FIA-MS instrumentation for monitoring of Ellman's reaction where both reactants (acetylthiocholine and 5,5’-dithiobis-2-nitrobenzoic acid, DTNB) and the reaction product (5-mercapto-2-nitrobenzoic acid) are monitored. This reaction is usually used for monitoring of acetylcholinesterase and butyrylcholinesterase. Due to its simplicity, the developed method is generally applicable for monitoring of enzymatic reactions of cholinesterases. The main advantage of this method is high selectivity and reduction of influence of compounds, which are reacting with DTNB, resulting in a color product of Ellman's reaction.
Illegal poisoning of wildlife and domestic animals is a worldwide issue. The carbamates primarily used as pesticides are often misused for such a purpose. In this study, 181 birds, mammals and baits were analysed over the period 2004-2009 for possible intoxication by carbamates. Intoxication by carbamate carbofuran was diagnosed in 89 cases, and in another 19 cases (nine Wild Boars and 10 Bisons) intoxication with another carbamate-methomyl - was proven. Incidental ingestion of the marten bait was the main cause of intoxication. Although the distribution of carbofuran was prohibited in 2007, no decline in the number of intoxicated animals in the following two years was detected. New cases of intoxication by carbofuran are anticipated in the future until all remaining stock is expended.
- MeSH
- acetylcholinesterasa analýza MeSH
- cholinesterasové inhibitory otrava škodlivé účinky toxicita MeSH
- chromatografie plynová MeSH
- financování organizované MeSH
- gastrointestinální obsah chemie MeSH
- histologické techniky MeSH
- játra chemie MeSH
- karbamáty otrava MeSH
- karbofuran otrava MeSH
- methomyl otrava MeSH
- organofosforové sloučeniny otrava toxicita MeSH
- otrava epidemiologie veterinární MeSH
- pesticidy otrava toxicita MeSH
- příčina smrti MeSH
- ptáci MeSH
- retrospektivní studie MeSH
- rezidua pesticidů analýza MeSH
- savci MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
V pokusech na samcích potkana byl sledován vliv farmakologické profylaxe Panpalem (pyridostig-min v kombinaci s benaktyzinem a trihexyfenidylem) na aktivitu enzymu acetylcholinesterázav plné krvi, bránici a vybraných částech mozku (frontální kúra, pontomedulární oblasti, hipokam-pus, mozeček) v 1. a 3. hodině neléčené a léčené (oxim HI-6 s atropinem) intoxikace organofosfo-rovým insekticidem fosdrinem. Zatímco v CNS nedošlo vlivem Panpalu ke statisticky významnýmzměnám aktivity acetylcholinesterázy v průběhu neléčené i léčené intoxikace fosdrinem, v krvia bránici Panpal výrazně prohloubil fosdrinem vyvolanou inhibici aktivity acetycholinesterázya navíc snížil reaktivační efekt oximu HI-6. Tyto údaje svědčí o důležitosti kombinace v profylaxiužívaného reverzibilního inhibitoru acetylcholinesterázy pyridostigminu s anticholinergiky, kteréby mohly eliminovat důsledky pyridostigminem vyvolaného poklesu aktivity enzymu na periferii.
In experiments on male rats the paper investigated the effect of pharmacological prophylaxis withPanpal (pyridostigmine in combination with benactyzine and trihexyphenidyl) on the activity ofacetylcholinesterase in the whole blood, diaphragm, and selected parts of the brain (frontal cortex,pontomedular region, hippocampus, cerebellum) at hour 1 and 3 of untreated and treated (oximeHI-6 with atropine) intoxication with the organophosphorous insecticide phosdrine. Whereas in theCNS Panpal did not produce statistically significant changes in the activity of acetylcholinesterasein the course of untreated and treated phosdrine intoxication, in the blood and diaphragm Panpalmarkedly intensified phosdrine-induced inhibition of the acetylcholinesterase activity and, inaddition, decreased the reactivating effect of the oxime HI-6. The data give evidence of theimportance of the combination of the prophylactically used reversible acetylcholinesterase inhibitorpyridostigmine with anticholinergics, which could eliminate the consequences of a pyridostigmine--induced decrease in the activity of the enzyme in the periphery.
- MeSH
- acetylcholinesterasa analýza účinky léků MeSH
- benaktyzin MeSH
- insekticidy antagonisté a inhibitory otrava MeSH
- krysa rodu rattus MeSH
- organofosforové sloučeniny antagonisté a inhibitory otrava MeSH
- pyridostigmin-bromid MeSH
- reaktivátory cholinesterázy farmakologie chemie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH
- MeSH
- acetylcholinesterasa analýza antagonisté a inhibitory MeSH
- acetyltransferasy analýza MeSH
- cholinergní antagonisté MeSH
- karnitin fyziologie MeSH
- krysa rodu rattus MeSH
- mozek enzymologie MeSH
- takrin farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH
