Miroslav Pohanka

..0005 s(-1). The half time (t(1/2)) of complex dissociation was 146 s. The achieved data appoint at fact that AChE could allow to distribute aflatoxins in body instead acting as a scavenger. Analytical impact of study is discussed, too...

..This review is focused on novel trends within such biosensors as a result of the known platform...

..The oxidative stress provoked by HI-6 and K628 was found to be significant on probability level P = 0.05. The others reactivators did not affect antioxidant levels...

..This review intends to summarize basic information about these bacterial agents. Military aspects of their pathogenesis and the detection techniques suitable for field use are discussed...

..Our study shows that biosensor technology could be used as a quick and cheap tool for testing of promising AChE inhibitors (AD drug candidates)...

..The pathogenesis of tularemia is still not fully understood. The main pathway is associated with proliferation in macrophages after activation by reactive oxygen species in phagosomes...

..The achieved limit of detection was 5 x 10(-8)M for paraoxon-ethyl and 5 x 10(-9)M for sarin and VX. Dipsticks were found stable for at least one month. Suitability of these dipsticks for routine assay is discussed...

..The last section tries to estimate future trends in research on biological warfare agents...

..Practical impact of described method is discussed...

..The principle of oxime reactivator function and a novel insight into AChE activity regulation and oxidative stress is discussed...

..The proposed method limit of detection was 2.45 nM, responding to 3.46 pg of methamidophos detected absolutely when we consider the sample volume...

..Repeatability of the developed method is discussed; the signal obtained from three different biosensors was 12.9+/-0.4 Hz for the sample containing 10(8) CFU/mL...

..The most surprising facts were found when the highest dose of 80 mg kg(-1) body weight of sulfur mustard was applied. While antioxidants were significantly increased, oxidants were decreased on an extensive scale...

..The purpose of the present study was to compare the response of these two rodents to a wild Francisella tularensis subsp. holarctica strain infection...

..The aim of the present study was to investigate biochemical and oxidative stress responses to experimental F. tularensis infection in European brown hares, an important source of human tularemia infections...

..Effects on liver, kidney and spleen were milder. We discuss ambivalent action of huperzine in the body and judge the huperzine action owing to recently reported experiments...

..The SAR was stated from obtained data. The former receptor studies were reported and discussed. The further in vivo studies were recommended in the view of OP pre-exposure treatment...

..Two newly prepared compounds were also chosen for docking studies that confirmed apparent π-π or π-cationic interactions aside the cholinesterases catalytic sites. The SAR findings were discussed...

..Consequently, the docking results confirmed the apparent π-π or π-cationic interactions with the key amino acid residues of hAChE and the binding of the chosen compound at the enzyme catalytic site...

..At a concentration of 10(-5) M, which is more common for human use, only methylchlorpyrifos-inhibited AChE was reactivated...

..Blood samples were collected before HI-6 application and after 30, 60, and 120 min. The overall HI-6 impact on organism is discussed...

..The SAR features concerning the non-oxime part of the reactivator molecule are also discussed...

..Three novel compounds showed promising results towards hAChE better to THA or 7-MEOTA. Three compounds resulted as potent inhibitors of hBChE. The SAR findings highlighted the C(6)-C(7)N-alkyl chains for cholinesterase inhibition...

..The structure-activity relationship (SAR) study confirmed the apparent influence of the xylene linkage and carbamoyl moiety on the reactivation ability and toxicity of the agents...

..HI-6 potential to produce nephropathy is hypothesized. The achieved conclusions were quite surprising and showed a complex impact of HI-6 on the body...

..As huperzine is a promising compound for AD treatment, our study was aimed at evaluating its pertinent implications in oxidative stress...

..In the case of cyclosarin- and soman-inhibited AChE, oxime K027 did not reach sufficient reactivation potency...

..Oximes can react - except their reactivating effect on cholinesterases - directly with cholinoreceptors. HI-6 is an oxime that may have an inhibitory effect on the muscarinic receptors, too...

..Though there is evidence of beneficial effects of melatonin, the substance was not investigated in greater details associated with specific regulation of oxidative stress in organs and tissues...

..The hepatotoxicity can be decreased by alternative ways of drug administration avoiding thus the first pass effect. The present study is aimed to investigate the influence of intramuscularly administrated tacrine on oxidative stress...

..Due to this, experiments on human tissue should be conducted after in vitro and in vivo tests on animals to eliminate such important failures of promising oximes...

..In case of BuChE reactivation, two compounds (K053 and K068) achieved similar results as obidoxime...

..There was also an observed lowering of reactivation efficacy when butyrylcholinesterase was exposed to trichlorfon for a longer time interval...

..The demonstrated effects of tularemia-induced pathology had a more extensive impact on the liver than on the spleen...

..However, the present experiments were carried out in order to assess the antioxidant effect of HI-6 in irradiated animals...

..The kinetics assay confirmed non-competitive inhibition of AChE by two best newly prepared compounds...

..Significant OS, depletion of low-molecular-mass antioxidants, increase in caspase activity, and some other processes related to SM action were determined. Moreover, we infer a principal role of OS in the tested organs...

..Additionally, HPLC technique was established to distinguish each prepared pyridinium analogue. This study represents universal method for preparation and identification of quaternary pyridinium detergents...

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..It is also needed by the fact that clinical findings considering this oxime are controversial...

..Hence, these oximes may be worthy of future development for the treatment of nerve agent intoxications, especially, with lipophilic agents such as soman and cyclosarin...

..Cerebral cortex tissues had decreased AChE and increased caspase 3 activities as well as the FRAP level. Owing to the novel findings, suitability of metrifonate for AD therapy is discussed...

..The research for drugs for Alzheimer's disease needs to focus on inhibitors that reduce the deposition of amyloid plaques, but do not initiate AChE expression...

..Cholinesterase inhibitors are substances, either natural or man-made that interfere with the break-down of ACh and prolong its action. Hence their relevance to toxicology and pharmacology...

..The best results were obtained using obidoxime where reactivation was near to 80%. Suitability of photometric microplates for following of reactivation procedures is discussed...

..The carbonyl levels were significantly increased due to SM, and the carbonylation was slowed due to melatonin intake. In conclusion, melatonin seems to be a prospective compound in reducing SM toxicity impact in the rat...

..The data also appoints at difficulty in antioxidant therapy as prophylaxis to the oxidative stress related toxins exposure and ambivalent modulation of oxidative stress...

..The minimal cholinesterase activity essential to survival is around 10%, when compared with the initial state. No changes in levels of low moleculary weight antioxidants were observed...

..This chapter briefly introduces the separate groups of chemical warfare agents together with their members and the potential therapy that should be applied in case someone is intoxicated by these agents...

..Partial protection of brain ChE against tabun inhibition was observed after administration of trimedoxime (acetylcholinesterase 20%; butyrylcholinesterase 30%) and obidoxime (acetylcholinesterase 12%; butyrylcholinesterase 16%)...

..Values for newly synthesized oximes were less than 10% for K206, K269 and K203...

..The most potent reactivators of inhibited BChE were K033, obidoxime, K117, bis-3-PA, K075, K074 and K127. The reactivation efficacy of tested oximes was lower in case of leptophos-oxon inhibited BChE...

..In this review, some strategies convenient for biosensor construction are presented. Solutions for cholinesterase immobilization and output signal monitoring are presented as the basic presumptions for successful biosensor construction...

..The methods employed in the study were advantageous in minimal sample volume consumption and fast acquisition of results...

..Administration of AChE inhibitors to the individuals suffering from tularemia is contra-indicatory. Drugs based on AChE inhibition should be restricted when tularemia or disease with a similar pathogenesis is suspected...

..Nevertheless, fast, sensitive, simple, portable, and low-cost devices are difficult to find. Application of biosensors appears to be a possible method to meet this need for mycotoxins assay...

..Owing to the significant role of cholinergic anti-inflammatory pathways in neuro-immunomodulation, we decided to examine the effect of galantamine on tularemia-infected BALB/c mice...

..Thus it can be advantageously used for accurate measurement of AChE activity. Suitability of assay for butyrylcholinesterase activity assessment is also discussed...

..R.S.D. of measurements was 2.3% for NMS and 2.4% for IMS, respectively. The developed method allows to indicate the presence of anti-tularemic antibodies shortly (1-3 days) after infection, one analysis is completed in 10min...

..All methods were verified using pooled human plasma samples and tested for potential interferents. 2,6-dichloroindophenol acetate is recommended as suitable substrate for BChE assay in clinical diagnostics...