In vitro and in vivo acetylcholinesterase-inhibiting effect of new classes of organophosphorus compounds

1999 ◽  
Vol 18 (2) ◽  
pp. 241-246 ◽  
Author(s):  
Murat Ozmen ◽  
Sadiye Sener ◽  
Ahmet Mete ◽  
Hasan Kucukbay
Keyword(s):  
Organophosphorus Compounds ◽  
Inhibiting Effect

scholarly journals A phosphorylation site in brain and the delayed neurotoxic effect of some organophosphorus compounds

1969 ◽  
Vol 111 (4) ◽  
pp. 487-495 ◽  
Author(s):  
M K Johnson
Keyword(s):  
Organophosphorus Compounds ◽  
Specific Binding ◽  
Phosphorylation Site ◽  
Test System ◽  
Binding Activity ◽  
Specific Component ◽  
Esterase Inhibitors ◽  
Brain And Spinal Cord

1. It is proposed that part of a neurotoxic dose of di-isopropyl phosphorofluoridate will be covalently bound in vivo to a specific component in the brain and spinal cord as the initial biochemical event in the genesis of the lesion. 2. A test system in vitro was devised that removes many di-isopropyl phosphorofluoridate-binding sites and indicates that the specific component may be a protein present in brain at a concentration comparable with that of the cholinesterases. 3. The site was found to be present and capable of binding di-isopropyl phosphorofluoridate in vitro in brain samples taken from either normal hens or those dosed with organophosphorus esterase inhibitors that are not neurotoxic. 4. Very little of the specific binding activity was found in brain samples from hens pre-dosed with a variety of neurotoxic organophosphorus compounds. 5. A solubilized preparation of the active brain component was obtained, suitable for further purification and study.

Desflurane Inhibits Hypoxic Pulmonary Vasoconstriction in Isolated Rabbit Lungs

1995 ◽  
Vol 83 (3) ◽  
pp. 552-556. ◽  
Author(s):  
Stephan A. Loer ◽  
Thomas W. L. Scheeren ◽  
Jorg Tarnow
Keyword(s):  
Minimum Alveolar Concentration ◽  
Pulmonary Arterial Pressure ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Constant Flow ◽  
Inhibiting Effect ◽  
Pulmonary Vasoconstriction ◽  
Pulmonary Arterial ◽  
Inspiratory Oxygen

Background Inhalational anesthetics inhibit hypoxic pulmonary vasoconstriction (HPV) in vivo and in vitro with a half-maximum inhibiting effect (ED50) within concentrations applied for general anesthesia. Because it is unknown whether desflurane acts likewise, we studied its effect on HPV in isolated blood-perfused rabbit lungs and compared its ED50 with that of halothane. Methods Isolated blood-perfused rabbit lungs were randomly allocated to treatment with either desflurane (n = 6) or halothane (n = 6). HPV, defined as an increase in pulmonary arterial pressure (PAP) at constant flow, was elicited by decreasing inspiratory oxygen concentration from 20% to 3% for 4 min. This effect was determined without (control HPV) and with increasing concentrations of the anesthetics (fraction of inspired carbon dioxide kept constant at 4.8 +/- 0.2%, perfusate temperature at 37 degrees C, and blood flow at 100 ml.min-1). Results Before exposure to the anesthetics, PAP increased by 8.6 +/- 1.9 cmH2O for all lungs within 4 min of hypoxia (control PAP for all lungs 19.6 +/- 2.5 cmH2O). Desflurane decreased this effect in a concentration-dependent fashion with an ED50 of 14.5%, compared with that of halothane, with an ED50 of 1.7%. Conclusions Assuming that 1 minimum alveolar concentration (MAC) values of desflurane and halothane for rabbits are 8.9% and 1.39%, respectively, this study yields ED50 values for the inhibition of HPV of approximately 1.6 MAC for desflurane and 1.2 MAC for halothane (P not statistically significant).

scholarly journals The Effect of Bialaphos on Ammonium-Assimilation and Photosynthesis I. Effect on the Enzymes of Ammonium-Assimilation

1989 ◽  
Vol 44 (1-2) ◽  
pp. 97-102 ◽  
Author(s):  
Aloysius Wild ◽  
Christine Ziegler
Keyword(s):  
Glutamine Synthetase ◽  
Glutamate Dehydrogenase ◽  
Ammonium Assimilation ◽  
Inhibiting Effect ◽  
Whole Plants ◽  
Leaf Homogenate

Abstract In this investigation, the effect of bialaphos (phosphinothricyl-alanyl-alanine) on the enzymes involved in NH4+-assimilation - glutamine synthetase, glutamine-2-oxoglutarate aminotransferase, glutamate dehydrogenase - is examined and compared to the effect of phosphinothricin (glufosinate) on the same enzymes. Bialaphos was given to whole plants (in vivo) and to leaf homogenate (in vitro). The investigation showed that bialaphos has an inhibiting effect on glutamine synthetase in vivo, but not in vitro. In contrast to this, phosphinothricin inhibits glutamine synthetase in vitro as well as in vivo. It was found that bialaphos, similar to phosphinothricin, does not inhibit glutamine-2-oxoglutarate aminotransferase and glutamate dehydrogenase in vivo or in vitro. Only at bialaphos concentrations exceeding 10 mM, there is an inhibition of glutamate dehydrogenase in vitro. Using radioactive [3H]bialaphos (phosphinothricyl-3H-alanyl-alanine) it could be demonstrated that in the plant, bialaphos is split into phosphinothricin and alanine. The phosphinothricin released is probably the active herbicide component. Consequently, the herbicidal effects of phosphinothricin and bialaphos are the same.

Test systems for in vivo and in vitro estimation of the risk and development of delayed neurotoxicity caused by organophosphorus compounds

2007 ◽  
Vol 41 (10) ◽  
pp. 516-518
Author(s):  
O. A. Khodakovskaya ◽  
N. A. Vodolazskaya ◽  
L. D. Glukhova ◽  
S. I. Timofeeva ◽  
S. I. Dvoretskaya ◽  
...  
Keyword(s):  
Organophosphorus Compounds ◽  
Delayed Neurotoxicity ◽  
Test Systems

scholarly journals THE ACTION OF SULFONAMIDES ON THE RESPIRATION OF BACTERIA AND YEAST

1942 ◽  
Vol 25 (6) ◽  
pp. 805-817 ◽  
Author(s):  
M. G. Sevag ◽  
M. Shelburne ◽  
Stuart Mudd
Keyword(s):  
Structural Similarity ◽  
Inhibitory Effect ◽  
Brewer’S Yeast ◽  
Respiratory Enzymes ◽  
Staph Aureus ◽  
E Coli ◽  
Brewer's Yeast ◽  
Inhibiting Effect

The inhibiting effects of sulfonamide drugs and their derivatives on the anaerobic decarboxylation of pyruvic acid by Staphylococcus aureus, Escherichia coli, baker's and brewer's yeast, and a carboxylase preparation from brewer's yeast have been investigated. These drugs are: sulfanilamide, sulfapyridine, sulfadiazine, sulfamethyldiazine, sulfathiazole, sulfamethylthiazole, sulfanilamido-5-ethyl-4-thiazolone, 2-aminopyrimidine, 2-aminothiazole, and 2-aminopyridine. The sulfathiazole ring appears to exercise decidedly greater specific inhibiting effect on the carboxylases of Staph. aureus and E. coli. The inhibiting effect on yeast carboxylase is non-differentiable among all the substances tried, except sulfamethyldiazine which is completely ineffective on the carboxylases of the organisms studied. The specific inhibitory effect of sulfathiazole on the carboxylases of Staph. aureus and E. coli in comparison to sulfanilamide, sulfapyridine, and sulfadiazine is in harmony with in vivo and in vitro experimental results of other investigators. The results of the present investigation appear to support the hypothesis (1) that sulfonamides exert their bacteriostatic action through chemical affinity for the carrier proteins of certain respiratory enzymes of the bacterial cell, and that this affinity may in part be related to structural similarity between components of the drugs and the corresponding respiratory coenzymes.

Brain Reaggregate Cultures in Neurotoxicological Investigations: Studies with Cholinergic Neurotoxins

1989 ◽  
Vol 16 (3) ◽  
pp. 221-230
Author(s):  
Christopher K. Atterwill
Keyword(s):  
Monolayer Culture ◽  
Organophosphorus Compounds ◽  
Whole Brain ◽  
Cholinergic Lesions ◽  
Low Concentrations ◽  
Testing Potential ◽  
Stepwise Procedure ◽  
Cholinergic Neurones

The number of neurotoxicants which produce ‘lesions’ in organotypic brain reaggregate cultures in vitro, which correlate with known in vivo actions, is growing. With respect to cholinergic neurones, this includes kainic acid, organophosphorus compounds and, in our hands, ethylcholine mustard aziridinium (ECMA) and aluminium. We have demonstrated that in vitro exposure to low concentrations of ECMA (12.5μM) produces a two-stage lesion in rat whole-brain reaggregate cultures, corresponding to initial direct inhibition of choline acetyltransferase (ChAT), followed by a later loss of cholinergic neurones. Higher concentrations of ECMA (25–50μM) are more generally cytotoxic and also cause lesions in non-cholinergic cerebellar granule neurones in monolayer culture. Aluminium (0.1–0.01mM) similarly reduces ChAT activity in rat whole-brain reaggregate cultures. Both agents may be useful in providing brain cholinergic lesions in vitro analagous to those occurring in types of dementia in vivo. The use of brain reaggregates in a ‘stepwise’ procedure for testing potential neurotoxicants is also described.

scholarly journals A conjugate of pyridine-4-aldoxime and atropine as a potential antidote against organophosphorus compounds poisoning.

2011 ◽  
Vol 58 (2) ◽  
Author(s):  
Jasna Lovrić ◽  
Suzana Berend ◽  
Ana Lucić Vrdoljak ◽  
Božica Radić ◽  
Maja Katalinić ◽  
...  
Keyword(s):  
Therapeutic Effect ◽  
Organophosphorus Compounds ◽  
Human Lymphocytes ◽  
Human Erythrocytes ◽  
Antidotal Activity

A conjugate of pyridine-4-aldoxime and atropine (ATR-4-OX) was synthesized and its antidotal efficiency was tested in vitro on tabun- or paraoxon-inhibited acetylcholinesterase (AChE) of human erythrocytes as well as in vivo using soman-, tabun- or paraoxon-poisoned mice. Its genotoxic profile was assessed on human lymphocytes in vitro and was found acceptable for further research. ATR-4-OX showed very weak antidotal activity, inadequate for soman or tabun poisoning. Conversely, it was effective against paraoxon poisoning both in vitro and in vivo. All animals treated with 5 % or 25 % LD(50) doses of the new oxime survived after administration of 10.0 or 16.0 LD(50) doses of paraoxon, respectively. Based on the persistence of toxicity symptoms in mice, the atropine moiety had questionable effects in attenuating such symptoms. It appears that ATR-4-OX has a therapeutic effect related to the reactivation of phosphylated AChE, but not to receptor antagonization.

Bispyridinium Oximes As Antidotal Treatment of Cyclosarin Poisoning—In Vitro and In Vivo Testing

2005 ◽  
Vol 24 (6) ◽  
pp. 399-402 ◽  
Author(s):  
Lucie Bartosova ◽  
Kamil Kuca ◽  
Daniel Jun ◽  
Gabriela Kunesova
Keyword(s):  
Rat Brain ◽  
Organophosphorus Compounds ◽  
Brain Homogenate ◽  
Chemical Structures ◽  
Hi 6 ◽  
In Vivo Testing ◽  
Acetylcholinesterase Enzyme ◽  
Enzyme Source

The mechanism of intoxication with organophosphorus compounds, including highly toxic nerve agents and less toxic pesticides, is based on the formation of irreversibly inhibited acetylcholinesterase, which causes cumulation of neuromediator acetylcholine in synaptic clefts and subsequent overstimulation of cholinergic receptors, that is followed by a generalized cholinergic crisis. Nerve agent poisoning is conventionally treated using a combination of a cholinolytic (atropine mostly) to counteract the accumulation of acetylcholine and acetylcholinesterase reactivators (pralidoxime or obidoxime) to reactivate inhibited acetylcholinesterase. In this study of cyclosarin poisoning treatment, oximes of different chemical structures (obidoxime, HI-6, BI-6, and HS-6) were tested in vitro on rat brain acetylcholinesterase (enzyme source: rat brain homogenate), and afterwards, they were tested in vivo in equimolar doses, in mice and rats. The HI-6 oxime appeared to be the most effective oxime in vitro and in vivo.

A comparison of the decontamination efficacy of foam-making blends based on cationic and nonionic tensides against organophosphorus compounds determinedin vitro and in vivo

2003 ◽  
Vol 22 (9) ◽  
pp. 507-514 ◽  
Author(s):  
J Cabal ◽  
J Kassa ◽  
J Severa
Keyword(s):  
Hydrogen Peroxide ◽  
Field Condition ◽  
Benzalkonium Chloride ◽  
Organophosphorus Compounds ◽  
Antagonistic Effects ◽  
In Vitro Methods ◽  
The Stability ◽  
And Control

The ability of foam-making blends to decontaminate the skin exposed to organophosphorus compounds was tested. The appropriate composition and rheological features (stability, grade of foaming) of tested blends were evaluated by in vitro methods and their ability to remove the contaminants from hard surface and to transform the contaminants into nontoxic compounds was evaluated byin vivo methods. The blends containing cationic and nonionic tensides as well as alkalized hydrogen peroxide seem to be the most efficacious to decontaminate the skin exposed to organophosphorus compounds according to the literature data. The composition of tested blends was optimized because particular components often have antagonistic effects. Cationic tensides support the reactivity of the blend and control the grade of foaming. Nonionic tensides control the stability of the foams but also react as retardants of the reactivity of the foams. Hydrogen peroxide is a real reacting component when it is transformed into hydrogen peroxide anion. It also acts as buffer if pH is higher than 11. Our in vivo results confirm that Desam OX (34 and 68%) and the foam-making blend containing benzalkonium chloride / Althosan MB (8%), Slovasol 2510 (2%) and hydrogen peroxide (3%) alkalized at pH 12 seem to be the most efficacious to remove contaminants (soman, VX) from the skin and transform them into nontoxic compounds. Therefore they could be used for primary decontamination of chemical casualties contaminated with nerve agents in the field condition.

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