Mutant of Bungarus fasciatus acetylcholinesterase with low affinity and low hydrolase activity toward organophosphorus esters. (1/6)

Enzymes hydrolysing highly toxic organophosphate esters (OPs) are promising alternatives to pharmacological countermeasures against OPs poisoning. Bungarus fasciatus acetylcholinesterase (BfAChE) was engineered to acquire organophosphate hydrolase (OPase) activity by reproducing the features of the human butyrylcholinesterase G117H mutant, the first mutant designed to hydrolyse OPs. The modification consisted of a triple mutation on the (122)GFYS(125) peptide segment, resulting in (122)HFQT(125). This substitution introduced a nucleophilic histidine above the oxyanion hole, and made space in that region. The mutant did not show inhibition by excess acetylthiocholine up to 80 mM. The k(cat)/K(m) ratio with acetylthiocholine was 4 orders of magnitude lower than that of wild-type AChE. Interestingly, due to low affinity, the G122H/Y124Q/S125T mutant was resistant to sub-millimolar concentrations of OPs. Moreover, it had hydrolysing activity with paraoxon, echothiophate, and diisopropyl phosphofluoridate (DFP). DFP was characterised as a slow-binding substrate. This mutant is the first mutant of AChE capable of hydrolysing organophosphates. However, the overall OPase efficiency was greatly decreased compared to G117H butyrylcholinesterase.  (+info)

Cycloheximide and disulfoton are positive in the photoclastogencity assay but do not absorb UV irradiation: another example of pseudophotoclastogenicity? (2/6)

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Clinical observation and comparison of the effectiveness of several oxime cholinesterase reactivators. (3/6)

After passing toxicity and experimental therapeutic tests, four oxime cholinesterase reactivators [PAM (pyridine aldoxime methiodide), PAC (pralidoxime, pyridine aldoxime methylchloride), TMB4 (trimedoxime), and DMO4 (obidoxime, Toxogonin, LuH6)] were compared in clinical trials. All of them proved capable of restoring erythrocyte cholinesterase activity and relieving symptoms and signs of organophosphate insecticide poisoning. Mildly and moderately poisoned patients can be treated by several injections of any one of these drugs alone, but severe cases need the synergistic action of atropine, as well as treatments for two to three consecutive days. Although response to treatment is stronger with TMB4 and DMO4, they are not recommended for routine treatment because of their dangerous adverse side effects.  (+info)

Prevention of acute parathion and demeton poisoning in farmers around Shanghai. (4/6)

After the occurrence of poisoning episodes among commune members who handled the insecticides parathion and demeton during the first few years of application in the early 1960s, a series of surveys was conducted and comprehensive regulatory actions were adopted. The surveys showed that the cause of most of the poisoning cases was percutaneous absorption of toxicant as a consequence of skin contamination during careless operating. As a result of a comprehensive program carried out by large numbers of administrators, health workers, and commune members, the incidence of intoxication quickly declined, starting in 1965, to a negligible level and has remained so to the present, even though parathion and demeton use has increased greatly. It is suggested that the experience obtained might be helpful to other areas in the People's Republic of China and in some developing countries.  (+info)

Response of the rat ileum, uterus and vas deferens to carbachol and acetylcholine following repeated daily administration of a cholinesterase inhibitor. (5/6)

1. Daily i.p. administration, for eight days, of the cholinesterase inhibitor disulfoton to rats produced mild to moderate signs of intoxication (tremors, incontinence and diarrhoea) but no deaths.2. Segments of ileum taken from the treated rats were subsensitive to carbachol but the vas deferens and the uterus did not exhibit any change in sensitivity to carbachol.3. The sensitivity to acetylcholine was increased in the ileum and vas deferens but not in the uterus.4. Acetylcholinesterase activity was 60-70% inhibited in all three tissues.  (+info)

Histopathological study of canine optic nerve retina treated by organophosphate pesticide. (6/6)

The fine structure of pathological changes was examined in the optic nerve and retina of beagle dogs after oral administration by capsule of the organophosphate pesticide ethylthiometon for 2 years. The optic nerve was invariably affected, and the number of myelinated axons markedly reduced. These were substituted for by delicate processes of astrocytes. Changes in the retina were mild and mainly seen in the peripapillary pigment epithelial cells and in the Muller cells of the peripheral retina. These histopathologic findings indicate that long-term administration of ethylthiometon involved both the optic nerce and selected portions of the retina.  (+info)