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Biomedical subjects

Jiri Patocka

Publications and source records attributed to Jiri Patocka.

4 recordsLinked to original sources

Tests with Daphnia magna: a new approach to prescreen toxicity of newly synthesized acetylcholinesterase reactivators.

Reactivators of phosphorylated acetylcholinesterase (oximes) are substances used as a human antidotal therapy for organophosphate poisoning. The objective of our study was to examine if juveniles of freshwater microcrustacean Daphnia magna could be employed as test animals in early screen toxicity tests of those substances as a first step for further experiments with daphnids intoxicated by organophosphates. For this purpose, seven different oximes were investigated. It was found that toxicity of all tested oximes increased with time. Mono-quaternary oximes were approximately ten fold (EC50, 14.9 mg.l(-1)) more toxic in 24 hour tests and five fold (EC50 was 79.46 mg.l(-1)) more toxic in 48 hour tests than bis-quaternary oximes. Tests with daphnids were shown to be easy to carry out at low cost and provided valuable results which could be used as a starting point for further research.

Acetylcholinesterase↗

Effect of humanin analogues on experimentally induced impairment of spatial memory in rats.

Humanin and its analogues have been shown to protect cells against death induced by various Alzheimer's disease genes and amyloid-beta-peptides in vitro: the analogue [Gly14]-humanin has also been shown to be potent in reversing learning and memory impairment induced by scopolamine in mice in vivo. It is important to validate these results by using other behavioral methods. In this study, the effect of [Gly14]-humanin and des-Leu-PAGA, another analogue (0.2 micromol kg(-1), i.p.) on the 3-quinuclidinyl benzilate-induced (2 mg kg(-1), i.p.) impairment of spatial memory in the multiple T-maze in rats has been evaluated. Both peptides reversed the impairment of spatial memory. These results indicate the potential of humanin analogues in modulation of the cholinergic system.

Amino Acid Sequence↗

Anthrax vaccines.

Anthrax, an uncommon disease in humans, is caused by a large bacterium, Bacillus anthracis. The risk of inhalation infection is the main indication for anthrax vaccination. Pre-exposure vaccination is provided by an acellular vaccine (anthrax vaccine adsorbed or AVA), which contains anthrax toxin elements and results in protective immunity after 3 to 6 doses. Anthrax vaccine precipitated (AVP) is administered at primovaccination in 3 doses with a booster dose after 6 months. To evoke and maintain protective immunity, it is necessary to administer a booster dose once at 12 months. In Russia, live spore vaccine (STI) has been used in a two-dose schedule. Current anthrax vaccines show considerable local and general reactogenicity (erythema, induration, soreness, fever). Serious adverse reactions occur in about 1% of vaccinations. New second-generation vaccines in current research programs include recombinant live vaccines and recombinant sub-unit vaccines.

Adverse Drug Reaction Reporting Systems↗

Determination of physostigmine and pyridostigmine in pharmaceutical formulations by capillary electrophoresis.

Physostigmine (PHY) and pyridostigmine (PYR) are two important anticholinesterase compounds with several clinical uses. Recently, PHY has been investigated for the treatment of senile dementia in Alzheimer's disease. However, both PHY and PYR have gained importance as antidotes for anticholinergic drugs. In military medicine, PYR is used as a prophylactic against nerve gas poisoning and was used in Saudi Arabia during the Gulf War in 1991. A new capillary zone electrophoresis (CZE) method for the rapid determination of PHY and PYR in pharmaceutical preparations has been developed. An untreated fused-silica capillary tube (75 microm i.d., 44 cm total length, 36.5 cm length to the detector) was employed with detection at 200 and 270 nm for PHY and PYR, respectively. The optimal separation conditions for PHY were: 50 mM boric acid-HCl buffer (pH 3.25) with 30 mM NaClO4, electrokinetic injection for 5 sec at -5 kV, temperature 25 degrees C, and separation voltage 15 kV. The optimal separation conditions for PYR were: 20 mM phosphate buffer (pH 7), electrokinetic injection for 20 sec at -10 kV, temperature 25 degrees C, and separation voltage 15 kV. The limits of detection (LOD, S/N = 3) were 70 and 60 ppb for PHY and PYR, respectively. The method can be used for the monitoring of possible main degradation products in tablets of military antidote formulations.

Chemistry, Pharmaceutical↗