Paddy cultivation is one of the widely planted crop in Malaysia. The growth of agricultural activity leads to the use of Organophosphate pesticide to protect the crop. This study is to determine the relationship between the levels of blood cholinesterase with the performance of motor coordination of children living in paddy farming area in Tanjung Karang, Selangor. This cross sectional study was conducted among 683 children from four schools in an agricultural area. Majority of the children have at a family member worked as farmer and was involved with pesticides. A set of questionnaire on the was given to the children to be filled by their parents. To measure their exposure to pesticide, blood cholinesterase levels were measured. Blood samples were taken through finger prick technique and were then analysed using LOVIBOND 412870 AF287. The children were administered with motor-coordination performance test using WHO Neurobehavioral Core Test Battery and McCarthy Learning Ability Scale. Young group children (6-85 years) showed a mean score of 56.66 in motor-coordination test while older group children (10-11)= years) scored a mean of 45.37. There was a significant relationship between blood cholinesterase level and motor coordination performance among the young-group children (r=0.215, p<0.001) and the older-group children (r=0.106, p=0.049). Based on the Linear Regression test results, total household income of family, and mode of transport used were found to have significant relationship with blood cholinesterase level of children in both groups. In addition, blood cholinesterase level and mothers’ occupation were found to have significant relationship with the motor-coordination performance of all children.
Organophosphate ; children ; blood cholinesterase ; motor-coordination

The introduction of musele relaxants was an epoch-making event in the development of clinical anesthesia and their use has hecome essential to anesthesia practice. Vecuronium, one of the newest muscle relaxant, has many advantages; it is rapid and short-acting, noncumulative, has minimal side reactions and is promptly antagonized by anticholinesterases was introduced recently our clinical anesthesia practice. Fortunately, domestic product of vecuronium as vecaron was introduced lately. Therefore, this study was performed to evaluate the effects of vecaron and as compare with vecuronium. The results were as follows: 1) Similar effects of muscle relaxation was observed in both group except the onset time of twitch depression was shorter in vecuronium group than vecaron group. 2) Blood pressure and heart rate was increased during intubation in groups. 3) Recovery index was slightly prolonged in vecuronium group than vecaron group but no significance was observed. However, this recovery index of vecuronium was slightly shorter than previous observations.
Anesthesia ; Blood Pressure ; Cholinesterase Inhibitors ; Depression ; Heart Rate ; Humans* ; Intubation ; Muscle Relaxation ; Vecuronium Bromide

OBJECTIVETo investigate the activity of ChE in rats poisoned by dimehypo and then treated with pralidoxime methylchloride or unithiol.

METHODRats were divided into control group (dimehypo); intervention groups [dimehypo plus pralidoxime methylchloride or dimehypo plus unithiol (sodium dimercaptopropanesulphonate)]. Rats were dosed with 4 different doses of dimehypo: 1/16, 1/8, 1/4 and 1/2 of LD50 respectively(the LD50 of dimehypo is 342 mg/kg). After being poisoned with dimehypo orally, rats were immediately injected intramuscularly with pralidoxime methylchloride or unithiol. The activity of ChE in blood was detected before and 1/2, 1, 2, 4 and 24 h after poisoning in dimehypo and intervention groups.

RESULTThe ChE activity of four dose subgroups at 1 h after poisoning were (1.04 +/- 0.21), (0.84 +/- 0.12), (0.71 +/- 0.12), (0.66 +/- 0.07) U/ml respectively; the ChE activity of pralidoxime methylchloride intervention groups were (1.01 +/- 0.18), (1.17 +/- 0.11), (1.01 +/- 0.04), (1.03 +/- 0.12) U/ml respectively; and the ChE activity of unithiol intervention groups were (1.15 +/- 0.15), (1.26 +/- 0.27), (1.08 +/- 0.08), (1.04 +/- 0.12) U/ml respectively. The inhibited ChE in blood was recovered by either treatment with pyraldoxime methylchloride or unithiol. These two drugs had similar effects of recovering the activity of ChE(P > 0.05), but at higher doses(1/4 and 1/2 of LD50) the effects of both were not so good.

CONCLUSIONPralidoxime methylchloride and unithiol could partly recover the activity of ChE inhibited by dimehypo.

Animals ; Antidotes ; pharmacology ; Cholinesterase Inhibitors ; poisoning ; Cholinesterases ; blood ; Dose-Response Relationship, Drug ; Insecticides ; poisoning ; Pralidoxime Compounds ; pharmacology ; Rats ; Unithiol ; pharmacology

OBJECTIVETo determine whether and to what degree the activity of cholinesterase(ChE) is inhibited by dimehypo at different doses of dimehypo [scientific name: 2-dimethylamine-1,3-bi(sodium hyposulfit)].

METHODRats were dosed with dimehypo or methamidophos orally, and were randomly divided into four subgroups according to the pesticide doses, which were 1/16, 1/8, 1/4 and 1/2 of LD50 respectively(the LD50 of dimethypo and methamidophos is 342 mg/kg and 20 mg/kg respectively). The activity of ChE in blood was determined before and 30 min, 1, 2, 4 and 24 h after exposure. The modified Ellman Method was employed to measure the activity of ChE.

RESULT1/16 LD50 dose of dimehypo did not affect the activity of ChE. When the dose increased, the activity of ChE decreased accordingly. 1/2 LD50 dose of dimehypo inhibited the activity of ChE by 35.9% compared with that of control group(P < 0.01). In rats dosed with methamidophos, even 1/16 LD50 dose inhibited the activity of ChE by 42.4% compared with that of control group. When the dose of methamidophos increased, the activity of ChE decreased accordingly. 1/2 LD50 dose of methamidophos inhibited the activity of ChE by 52.9%. The activity of ChE in the rats dosed with dimehypo at various doses was significantly lower than that in the rats dosed with corresponding doses of methamidophos(P < 0.01).

CONCLUSIONHigher doses of dimehypo may inhibit the activity of ChE. However, as compared with methamidophos, dimehypo is a weaker inhibitor of ChE.

Animals ; Cholinesterase Inhibitors ; toxicity ; Cholinesterases ; blood ; Dose-Response Relationship, Drug ; Insecticides ; toxicity ; Lethal Dose 50 ; Organothiophosphorus Compounds ; toxicity ; Rats

AIMTo establish chiral separation method for donepezil hydrochloride (E2020) enantiomers by capillary electrophoresis (CE) and determine the two enantiomers in plasma.

METHODSAlkalized plasma was extracted by isopropanol-n-hexane (3 : 97) and L-butefeina was used as the internal standard. Enantioresolution was achieved using 2.5% sulfated-beta-cyclodextrin as chiral selector in 25 mmol x L(-1) triethylammonium phosphate solution (pH 2.5) on the uncoated fused-silica capillary column (70 cm x 50 microm ID). The feasibility of the method to be used as quantitation of E2020 enantiomers in rabbit plasma was also investigated.

RESULTSE2020 enantiomers were separated at a baseline level under the above condition. The linearity of the response was evaluated in the concentration range from 0.1 to 5 mg x L(-1). The linear regression analysis obtained by plotting the peak area ratio (A(s)/A(i)) of the analyte to the internal standard versus the concentration (C) showed excellent correlation coefficient (r = 0.999 2 for R(-)-E2020, r = 0.999 7 for S(+)-E2020) and the equations were A(s)/A(i) = 0.024 2 + 0.289 2C and A(s)/A(i) = 0.010 8 + 0.273 7C, respectively. The low limit of detection was 0.05 mg x L(_1). The inter- and intra-day precision (RSD) were all less than 20% .

CONCLUSIONCompared with CSP by HPLC, the CE method is simple, reliable, inexpensive and suitable for studying the stereoseletive pharmacokinetics in rabbits.

Animals ; Cholinesterase Inhibitors ; analysis ; blood ; chemistry ; Electrophoresis, Capillary ; methods ; Female ; Indans ; analysis ; blood ; chemistry ; Male ; Piperidines ; analysis ; blood ; chemistry ; Rabbits ; Stereoisomerism ; beta-Cyclodextrins

AIMTo establish a sensitive and specific liquid chromatography-mass spectrometry (time-of-flight) [LC-MS (TOF)] method for the determination of donepezil in human plasma after an oral administration of 5 mg donepezil hydrochloride tablet.

METHODSAlkalized plasma was extracted with isopropanol-n-hexane (3:97) and loratadine was used as internal standard. Solutes were separated on a C18 column with a mobile phase of methanol-acetate buffer (pH 4.0) (80:20). Detection was performed on a time-of-flight mass spectrometry equipped with an ESI interface and operated in positive-ionization mode. Donepezil quantitation was realized by computing the peak area ratio (donepezil-loratadine) (donepezil m/z 380[M + H]+ and loratadine m/z 383[M + H]+) and comparing them with calibration curve (r = 0.9998).

RESULTSThe linear calibration curve was obtained in the concentration range of 0.1-15 micrograms.L-1. The detection limit of donepezil was 0.1 microgram.L-1. The average recovery was more than 90%. The intra- and inter-run precision was measured to be below 15% of RSD.

CONCLUSIONThe method is sensitive, simple and rapid, so, it can meet the need of the studies on the pharmacokinetics and bioavailability of donepezil.

Cholinesterase Inhibitors ; blood ; pharmacokinetics ; Chromatography, High Pressure Liquid ; methods ; Humans ; Indans ; blood ; pharmacokinetics ; Mass Spectrometry ; methods ; Piperidines ; blood ; pharmacokinetics ; Spectrometry, Mass, Electrospray Ionization

BACKGROUNDThe nervous system, through the vagus nerve and its neurotransmitter acetylcholine, can down-regulate the systemic inflammation in vivo, and recently, a role of brain cholinergic mechanisms in activating this cholinergic anti-inflammatory pathway has been indicated. Galanthamine is a cholinesterase inhibitor and one of the centrally acting cholinergic agents available in clinic. This study aimed to evaluate the effect of galanthamine on circulating tumor necrosis factor alpha (TNF-alpha) in rats with lipopolysaccharide-induced peritonitis and the possible role of the vagus nerve in the action of galanthamine.

METHODSRat models of lipopolysaccharide-induced peritonitis and bilateral cervical vagotomy were produced. In the experiment 1, the rats were randomly divided into control group, peritonitis group, and peritonitis groups treated with three dosages of galanthamine. In the experiment 2, the rats were randomly divided into sham group, sham plus peritonitis group, sham plus peritonitis group treated with galanthamine, vagotomy plus peritonitis group, and vagotomy plus peritonitis group treated with galanthamine. The levels of plasma TNF-alpha were determined in every group.

RESULTSThe level of circulating TNF-alpha was significantly increased in rats after intraperitoneal injection of endotoxin. Galanthamine treatment decreased the level of circulating TNF-alpha in rats with lipopolysaccharide-induced peritonitis, and there was significant difference compared with rats with lipopolysaccharide-induced peritonitis without treatment. The 3 mg/kg dosage of galanthamine had the most significant inhibition on circulating TNF-alpha level at all the three tested doses. Galanthamine obviously decreased the TNF-alpha level in rats with lipopolysaccharide-induced peritonitis with sham operation, but could not decrease the TNF-alpha level in rats with lipopolysaccharide-induced peritonitis with vagotomy.

CONCLUSIONCholinesterase inhibitor galanthamine has an inhibitory effect on TNF-alpha release in rats with lipopolysaccharide-induced peritonitis, and the vagus nerve plays a role in the process of the action of galanthamine.

Animals ; Cholinesterase Inhibitors ; therapeutic use ; Galantamine ; therapeutic use ; Lipopolysaccharides ; toxicity ; Male ; Peritonitis ; blood ; chemically induced ; drug therapy ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo study the new method of monitoring and clearing organophosphate in blood during single or mixed organophosphate(OP) poisoning.

METHOD(1) Mixed equal volumes of blood of OP poisoned rat and healthy rat, then determine whole blood cholinesterase (ChE) activity. The descending range of ChE activity represents the level of residual OP in blood. (2) Poisoned rats by single or mixed OP pesticides were injected with 5% NaHCO3 15 ml/kg intraperitoneally, then the level of OP in blood was detected.

RESULTS(1) The monitoring results of blood residual OP by gas chromatography were similar to that by "Mixes blood method", which showed significant difference(P < 0.05) from that before OP administration. (2) NaHCO3 injection could not improve the toxic symptoms and whole blood or brain ChE inhibition in 10 CP poisoned rats, blood residual OP level was also not affected, but lung pathological changes by OP such as interstitial inflammation and oedema showed some relief.

CONCLUSIONThe monitoring of blood ChE by "mixed blood method" may reflect the general level of the blood residual OP within the range of exposure dose. The effect of NaHCO3 was not satisfactory, but it may improve OP-induced lung pathological changes.

Animals ; Cholinesterase Inhibitors ; poisoning ; Cholinesterases ; blood ; Chromatography, Gas ; Insecticides ; poisoning ; Lung ; pathology ; Organophosphate Poisoning ; Organophosphorus Compounds ; blood ; Rats ; Sodium Bicarbonate ; pharmacology

Blood Platelets/*drug effects ; Blood Platelets/enzymology ; Cholinesterase Inhibitors/*adverse effects ; Models, Animal ; Movement/*physiology ; Platelet Aggregation/*drug effects ; Pyridostigmine Bromide/*adverse effects ; Work/*physiology

BACKGROUND: There have been some conflicting reports showing that muscle relaxants and anticholinesterases affect the level of the bispectral index (BIS). The purpose of this study was to investigate whether pyridostigmine affects the level of the BIS during recovery from sevoflurane anesthesia. METHODS: Fifty-two adult patients scheduled for laparoscopic cholecystectomy and laparoscopic appendectomy. Anesthesia was induced with thiopental 4 mg/kg and rocuronium 0.6 mg/kg. The lung was mechanically ventilated with 1-3 vol% sevoflurane, 50% oxygen and 50% nitrous oxide. After a specimen was removed, the sevoflurane concentration was maintained at 1.5 vol%. When skin closure began, sevoflurane was stopped; however, 50% oxygen and 50% nitrous oxide were maintained. The patients then received either (1) a group that received an injection of glycopyrrolate 0.04 mg/kg and pyridostigmine 0.2 mg/kg (reverse (R) group, n = 26) or (2) a group that received normal saline (control (C) group, n = 26). Group assignment was random. Pyridostigmine, a reversible cholinesterase inhibitor, is a parasympathomimetic. End-tidal sevoflurane concentration, train of four (TOF) ratio, bispectral index (BIS), blood pressure and heart rate were measured from the end of the operation to 15 min after inject of pyridostigmine or placebo. RESULTS: There were no significant between group differences in the time dependent decrease in end-tidal sevoflurane concentration (P = 0.0642). There were significant differences between the two groups for the time course for increases in the TOF value (P < 0.0001). There were significant differences between the two groups for the time course for increases in the BIS value (P = 0.0107). There were no significant differences in the mean BIS value up to 10 minutes after administering drug, but 15 minutes after administrating the reverse drug or the control drug, the BIS value showed significantly different BIS values: 68.2 +/- 6.2 (Group R) and 63.2 +/- 6.2 (Group C) (P = 0.0058). CONCLUSIONS: The finding that pyridostigmine increases TOF and BIS suggests that pyridostigmine may enhance recovery during recovery from sevoflurane anesthesia.
Adult ; Androstanols ; Anesthesia ; Appendectomy ; Blood Pressure ; Cholecystectomy, Laparoscopic ; Cholinesterase Inhibitors ; Cholinesterases ; Glycopyrrolate ; Heart Rate ; Humans ; Lung ; Methyl Ethers ; Muscles ; Nitrous Oxide ; Oxygen ; Pyridostigmine Bromide ; Skin ; Thiopental