Continual monitoring of the reactivation effect of oximes on blood acetylcholinesterase in the rats poisoned with organophosphates.

Acetylcholinesterase activity in rat blood was continuously monitored following O-ethyl-S-(2-dimethylaminoethyl)-methylphosphonothioate intoxication (p.o.) alone and in combination with atropine and the reactivators trimedoxime, obidoxime and methoxime. Decrease of acetylcholinesterase activity was not influenced by atropine alone but following treatment with a combination of atropine with the reactivators mentioned, an increase (reactivation) of the blood enzyme was demonstrated. This increase was highest for the combination atropine-trimedoxime and the lowest for the combination atropine-obidoxime.

Capillary zone electrophoretic determination of some drugs against Alzheimer's disease.

A new capillary zone electrophoresis (CZE) method for the determination of tacrine (THA), 7-methoxytacrine (7-MTHA) and their basic metabolites (THAm, 7-MTHAm) in pharmaceutical and biological samples (urine and serum) was developed. Separation of all compounds by CZE was carried out using a 46.6 cm untreated fused-silica capillary applying 20 kV separation voltage using 50 mM phosphate buffer of pH 2.8 for THA and THAm and of pH 7.8 for 7-MTHA and 7-MTHAm as background electrolyte (BGE). Detection was carried out at 240 nm (THA and THAm) and 248 nm (7-MTHA and 7-MTHAm). THA and THAm were separated in less than 4 min while 7-MTHA and 7-MTHAm were separated in less than 7 min. The detection limits (SIN = 3) obtained were 3 ppb for THA and 4 ppb for 7-MTHA in aqueous solutions; 50 ppb for THA and 47 ppb for 7-MTHA for the determination in urine (diluted 1:10); 52 ppb for THA and 56 ppb for 7-MTHA, in deproteinized serum samples. The methods are suitable for therapeutic drug monitoring of the drugs.

Fluoride plus aluminum: useful tools in laboratory investigations, but messengers of false information.

Aluminofluoride complexes (AlF(x)) form spontaneously in aqueous solutions containing fluoride and traces of aluminum ions and appear to act as phosphate analogs. These complexes have become widely utilized in laboratory investigations of various guanine nucleotide-binding proteins. Reflecting on many laboratory studies, a new mechanism of fluoride and aluminum action on the cellular level is being suggested. The long-term synergistic effects of these ions in living environment and their hidden danger for human health are not yet fully recognized.

Acute toxicities of 2-dialkylaminoalkyl-(dialkylamido)-fluoro-phosphates.

Toxicities expressed as LD50 values of 2-dialkylaminoalkyl-(dialkylamido)-fluorophosphates for rats and mice (i.m. administration) were determined. Rats were more sensitive to these compounds than mice: LD50 values varied from 17 (rats) to 1222 (mice) micrograms/kg. LD50 values at different routes of administration (i.v., i.m., s.c., p.o. and p.c.) for one derivative of this group, 2-dimethylaminoethyl-(dimethylamido)-fluorophosphate, were determined. Depending on the route of administration, LD50 values varied from 11 (i.v.) to 190 (p.o.) micrograms/kg for rats and from 27.6 (i.v.) to 222 (p.o.) micrograms/kg for mice, respectively. Percutaneous toxicity in rats only (LD50 = 1366 micrograms/kg) was determined.

Effect of 7-methoxytacrine and L-carnitine on the activity of choline acetyltransferase.

Changes of choline acetyltransferase (ChAT) activity in the hippocampus and the basal ganglia were studied in rats treated i.p. with L-carnitine (CRT) and 7-methoxytacrine (7-MEOTA) (i.m.) separately or 3-days treated with L-carnitine and then with one administration of 7-MEOTA. Both compounds increased ChAT activity when administered separately. 3-day treatment of CRT followed by administration of 7-MEOTA normalized ChAT activity.

Determination of drugs used as anti-Parkinson's disease drugs in urine and serum by capillary electrophoresis.

A new capillary electrophoresis method to determine simultaneously eight of the most important anti-Parkinson's disease compounds has been developed. The generic names of the drugs studied are benactyzine (BA), trihexyphenidyl (TP), fenpiverin (FP), diphemin (DF), scopolamine (BL), adiphenine (TS), diethylaminoethylester 1-phenylcyclopentane-1-carboxylate (EKK), and diethylaminoethylester tetramethoxydiphenylacetate (EKO). An untreated fused-silica capillary tube (75 microns i.d., 57 cm total length, 49.5 cm length to the detector) was used with detection at 190 nm. The optimal separation conditions were 50 mM phosphate buffer (pH 2.7) with 7 mM-beta-cyclodextrin, electrokinetic injection for 15 sec at 5 kV, temperature 25 degrees C, and 15-20 kV separation voltage. Complete separation of all compounds was achieved in less than 16 min. The procedure was applied for the determination in urine and serum. The limits of detection (LOD, S/N = 3) for serum were 209 (FP), 234 (EKO), 168 (DF), 182 (BA), 168 (TP), 220 (BL), 174 (TS), and 163 (EKK) ppb. The method can be used for the therapeutic drug monitoring of these central active cholinolytics in clinical laboratories.

Chemical agents and chemical terrorism.

Chemical terrorism is a new threat to the security of mankind, which scale essentially exceeds the impact of use of the most modem firearms. At present time all over the world threats from different radical elements to use radioactive materials, potent poisonous substances and pathogenic microorganisms for terrorist purposes became more frequent. High-toxic chemical substances can fall in terrorist hands through wide range of sources. Potentially misused types of chemical compounds are discussed in this article.

Huperzine A--an interesting anticholinesterase compound from the Chinese herbal medicine.

Huperzine A, alkaloid from the Chinese herbal medicine Qian Ceng Ta, which is prepared from the moss Huperzia serrata, has been used in China for centuries to treat fever and inflammation. Huperzine A is a strong inhibitor of cholinesterases with high selectivity to acetylcholinesterase and in China is developed as therapeutic against Alzheimer's disease. May be that huperzine A will be better than other centrally active anticholinesterases in treating this neurodegenerative disorder. Huperzine A appears to have additional pharmacological properties that make it an attractive candidate therapy for clinical trials.

Central cholinergic nervous system and cholinergic agents.

Central cholinergic nervous system play important role in many physiological and behavioral functions in humans. The activity of the cholinergic nervous system depends upon the production and fate of acetylcholine and all compounds influenced its biosynthesis, storage, release, hydrolysis, interaction with different subtypes of cholinergic receptors, etc., there are very important drugs and therapeutics. This paper summarizes current views on many compounds which can interact with different parts of central cholinergic nervous system.

Anti-inflammatory triterpenoids from mysterious mushroom Ganoderma lucidum and their potential possibility in modern medicine.

Ganoderma lucidum, a mushroom long used in the East for a broad range of disorders, contains numerous pharmacologically active compounds. Very important of them are highly oxygenated anti-inflammatory triterpenes, which are the aim of this mini-review.

The toxins of Cyanobacteria.

Cyanobacteria, formerly called "blue-green algae", are simple, primitive photosynthetic microorganism wide occurrence in fresh, brackish and salt waters. Forty different genera of Cyanobacteria are known and many of them are producers of potent toxins responsible for a wide array of human illnesses, aquatic mammal and bird morbidity and mortality, and extensive fish kills. These cyanotoxins act as neurotoxins or hepatotoxins and are structurally and functionally diverse, and many are derived from unique biosynthetic pathways. All known cyanotoxins and their chemical and toxicological characteristics are presented in this article.

The most important microtubule natural inhibitors.

Natural microtubule inhibitors represent chemically very variegated family of structures with strong effect on cytoskeletal functions and the use of them is one of the most frequent therapeutic strategies for carcinoma treatment. The survey of the most important natural microtubule inhibitors is summarized in this paper.

Natural polyamines and their biological consequence in mammals.

The polyamines (putrescine, cadaverine, agmatine, spermidine and spermine), wide-spread in all organisms, have been shown to play a role in regulation of growth and differentiation of virtually all types of cells. Their role in many physiological and pathophysiological processes have been studied very intensively during the last two decades. Inhibitors of polyamine biosynthesis have potential clinical uses as antitumor and antiparasitic agents. The brief summary with regard to their biological consequences in mammals is discussed in this paper.

3-Nitropropionic acid and similar nitrotoxins.

3-Nitropropionic acid as well as 3-nitro-1-propanol and its beta-D-glucopyranoside (miserotoxin) are the plant and fungal toxins reported to interrupt mitochondrial electron transport resulting in cellular energy deficit. These nitrotoxins induce neurological degeneration in ruminants and humans. 3-Nitropropionic acid-intoxicated rats serve as the animal model for Huntington's disease.

[Toxins from the aspect of international control programs]. / Toxiny z pohledu mezinárodních kontrolních rezimu.

Toxins, chemical substances produced by practically all forms of life, represent a chemically broad group of compounds. Many of them are very toxic for human and represent a serious jeopardy because they may be misused through chemical warfare or terrorist attacks. This danger has been increasing recently because toxins are more and more available due to modern synthetic methods and application of genetic engineering. Therefore the international community adopted multilateral conventions and control regimes, which regulate handling with toxins. These fundamentals are implemented into the Czech system of law too.

Novel acetylcholinesterase reactivator K112 and its cholinergic properties.

The oxime reactivator K112 is a member of the new group of xylene linker-containing AChE reactivators. Its cholinergic properties could be of importance at OP poisoning and are not related to the AChE reactivation that has been studied. It has been found that, despite of reactivating potency, this compound has additional effects. These cholinergic effects include a weak inhibition of AChE (IC(50)=43.8 ± 4.88 µM), inhibition of binding to the porcine muscarinic M2 receptor (IC(50)=4.36 µM) and finally, the inhibition of HACU (68.4 ± 9.9%), a key regulatory step in the synthesis of ACh. The inhibition of the binding of (3H)-HC-3 (64.7 ± 4.7%) and the influence on the membrane fluidity have also been observed. Blocking properties of K112 on the muscarinic receptors have been revealed in the in vitro experiment (rat urinary bladder) and in the in vivo experiment (rat heart BPM) as well. All these cholinergic properties could significantly contribute to the antidotal effect of K112 at the poisoning by the organophosphates.