Red Blood Cell Cholinesterase Research Articles

Predicting outcome in organophosphorus poisoning using RBC cholinesterase and serum cholinesterase values: A hospital-based longitudinal study

Objectives: Organophosphorus (OP) poisoning is a leading cause of mortality due to self-harm in Asian countries, including India. Red blood cell cholinesterase (RBC-ChE) and serum cholinesterase (serum-ChE) levels are used for predicting outcomes. There is a paucity of literature studying the RBC-ChE levels in OP poisoning and comparing it with the serum-ChE levels. Materials and Methods: This is a longitudinal study assessing the outcome in OP poisoning patients using the RBC-ChE and serum-ChE levels. Both enzyme levels are compared and correlated for adult patients presenting within 24 hours of consumption of the OP compound. Sensitivity and specificity are measured. Statistical Analysis: Data were analyzed using SPSS v21. Results of descriptive statistics were expressed as mean T standard deviation (SD) for normally distributed data or median (interquartile range [IQR]) for skewed data for continuous variables and frequency (percentage) for categorical variables. Results: Of the 99 OP poisoning patients included, 20 patients did not survive, and 23 patients required ventilatory support. At admission, RBC-ChE (median, interquartile range [IQR]) was significantly different between survivors (45.2 [30.5–60] U/g Hb) and nonsurvivors (6.3 [4.2–13.4] U/g Hb), while serum-ChE (median, IQR) was not statistically different (p ¼ 0.061) between survivors (350 [247–670]) and nonsurvivors (290 [182–415.8]). Similarly, RBC-ChE was significantly different between patients requiring a ventilator and those not requiring a ventilator (6.8 vs. 44.2 U/g Hb), whereas the serum-ChE values measured on admission were not significantly different for patients requiring a ventilator versus those not requiring a ventilator (290 vs. 348 U/L; p ¼ 0.119). At the cutoff of 20 U/g Hb, RBC-ChE had 90.5% sensitivity and 91% specificity in predicting mortality. Kaplan–Meier survival showed the probability of survival decreased to nearly 50% if the time to reach the hospital was ≤4 hours. Conclusion: RBC-ChE was superior in predicting outcomes in OP poisoning patients compared with serum-ChE measured on the day of admission.

Organophosphate poisoning from inappropriate topical use of malathion pesticide: A case report

A 43-year-old male with no past medical history presented to our emergency department with vomiting, diarrhea, and abdominal pain of 3 h’ duration. Upon further questioning, he revealed that he had been applying malathion pesticide over his body for the past 3 days for self-diagnosed scabies. He was otherwise afebrile and hemodynamically stable, and the physical examination was unremarkable. The patient was diagnosed with organophosphate poisoning and treated symptomatically due to the lack of worrying cardiorespiratory or neurologic sequelae. He was subsequently admitted to the general ward, where his symptoms abated within 4 h. Serum and red blood cell cholinesterase tests sent on admission returned on day three and were significantly decreased (serum cholinesterase 2131 U/L, reference range 4700–12000 U/L; red blood cell cholinesterase 3365 U/L, reference range 7700–14600 U/L). He was discharged home well and stable on day 5 of admission, with outpatient psychiatric follow-up for likely delusional parasitosis.

Preliminary Toxicological Studies On 0, 0-diethyl, 0(2-isopropyl -6. Methyl - 4, Pyrimidinyl) Phosphorothioate (Diazinon) In Balami Sheep.

Toxicity studies of 0,0-diethyl-0-(2- isoprophyl-6-methyl-4-pyrimidinyl) phosphorothioate (DiazinonR) was carried out in the Balami breed of sheep. The agent was administered orally daily for one week at the rate of 20, 25 and 30mg/kg body weight to groups of sheep. The 30mg/kg dose produced transient clinical signs in the sheep. Diazinon inhibited plasma and red blood cell cholinesterase activity. The intensity of the inhibition was more with 30mg/kg dose and occurred as from day 3 and lasted till the end of the investigation 7 days post treatment. Leucocytosis was also observed with the 30mg/kg dose. There was no observable effect of the chemical on the RBC, Hb, and PCV values in sheep at the dosages used.

The Lower Levels of Serum and RBC Cholinesterase in Acute Opioid Poisoning

Background: Cholinesterase is an enzyme that plays a critical role in regulating neural transmission. Many factors may decrease the cholinesterase levels in serum and Red Blood Cells (RBCs). It is suggested that the use of opium may effectively change the levels of Cholinesterase in serum and RBCs. This study aimed to evaluate the serum and RBC levels of cholinesterase in patients who were acutely poisoned with opium. Methods: This cross-sectional study was conducted in 65 patients suffering from acute opium poisoning. The serum levels of cholinesterase were measured using an automated analyzer. The levels were also measured in RBCs, using a colorimetric method. Simultaneously, 65 patients served as the positive controls from among those poisoned with organophosphates. Results: The serum cholinesterase levels were lower than the normal range in 16.9% of patients poisoned with opium and in 76.9% of those poisoned with organophosphate agents (P<0.001). Similarly, the levels of RBC cholinesterase were lower than the normal range as found in 64.6% and 15.4% of patients poisoned acutely with opium (Group 1) and organophosphate (Group 2), respectively (P<0.001). Conclusion: Acute opium poisoning effectively reduced both the levels and activities of cholinesterase in the patients’ serum and RBCs significantly different from those noted in patients suffering from organophosphate toxicity.

Nerve conduction study as a diagnostic tool in atypical presentation of accidental organophosphorus poisoning

Poisoning with organophosphorus (OP) compounds is a worldwide phenomenon. However, atypical presentation of OP toxicity, particularly when there is a paucity of muscarinic manifestations, can be a diagnostic challenge. We report a patient with atypical symptoms where exposure to OP poison was not clearly determined. Motor nerve conduction studies done to rule out acute motor neuropathy revealed that a single supramaximal stimulus-evoked repetitive compound motor action potentials. As this finding is the earliest and most sensitive indicator of acetylcholine esterase inhibition, OP poisoning was suspected. Decreased plasma acetylcholinesterase levels confirmed the diagnosis. The patient recovered completely with treatment. Although the diagnostic hallmark of OP poisoning is a reduction in serum and red blood cell cholinesterase activity, clinicians should be alert to recognize evidence of neuromuscular transmission failure seen on nerve conduction study to diagnose atypical or concealed cases of OP poisoning.

The use of the Electrometric Method in Measuring the Activity of Cholinesterase in Local Female Buffalo in north of Iraq

The aim of present study, was desigen to measurement of cholinesterase (ChE) activity by electrometric method in normal blood of adult Female buffalo, Cholinesterase was used in red blood cells (RBCs)to determine the linear relationship between incubation time and cholinesterase activity. The change in pH of RBCs cells reaction mixture (0.21 to 0.47) agreed with increased incubation time of 10 - 50 minutes and the pH change red blood cells reaction mixture (0.31 to 0.46) was associated with increased incubation temperature of 25-40C. recorded the highest activity of natural ChE the change in pH / 40 C° minutes in the red blood cells (0.46), whole blood (0.42) and least in the blood plasma (0.076). To illustrate the accuracy of the way the coefficient of variation in red blood cells and blood plasma and the whole blood (1.65%, 6.97% and 4.12%), respectively, this was done using 0.1 ml acetylcholine iodide 7.5% as the basis of the combination interaction of the current study. Quinidine sulfate specifically inhibited pseudo ChE in the RBC and whole blood, and it was estimated to be (6.5%,16.7%), where as true ChE activity was (93.5%, 83.3%). Monocrotophos at concentration (0.5, 1 µM) and carbaryl at (5, 10 µM) significantly inhibited RBCs ChE in vitro. These results indicate that the used of modified electrometric method its simple, precise, efficient and have the validity for measurement of ChE activities in adult Female of buffalo.

Sarin Exposures in A Cohort of British Military Participants in Human Experimental Research at Porton Down 1945-1987.

The effects of exposure to chemical warfare agents in humans are topical. Porton Down is the UK's centre for research on chemical warfare where, since WWI, a programme of experiments involving ~30000 participants drawn from the UK armed services has been undertaken. Our aim is to report on exposures to nerve agents, particularly sarin, using detailed exposure data not explored in a previous analysis. In this paper, we have used existing data on exposures to servicemen who attended the human volunteer programme at Porton Down to examine exposures to nerve agents in general and to sarin in particular. Six principal nerve agents were tested on humans between 1945 and 1987. Of all 4299 nerve agent tests recorded, 3511 (82%) were with sarin, most commonly in an exposure chamber, with inhalation being the commonest exposure route (85%). Biological response to sarin exposure was expressed as percentage change in cholinesterase activity and, less commonly, change in pupil size. For red blood cell cholinesterase, median inhibition for inhalation tests was 41% (interquartile range 28-51%), with a maximum of 87%. For dermal exposures the maximum inhibition recorded was 99%. There was a clear association between increasing exposure to sarin and depression of cholinesterase activity but the strength and direction of the association varied by exposure route and the presence of chemical or physical protection. Pupil size decreased with increased exposure but this relationship was less clear when modifiers, such as atropine drops, were present. These results, drawn from high quality experimental data, offer a unique insight into the effects of these chemical agents on humans.

Variable response of cholinesterase activities following human exposure to different types of organophosphates.

We investigated the red blood cell (RBC) acetylcholinesterase (AChE) activities and butyrylcholinesterase (BChE) activities at presentation to the emergency department (ED) and at 24 h after presentation following poisoning by dichlorvos, fenitrothion, or ethyl p-nitrophenol thio-benzene phosphonate (EPN). Although the patients from different groups had similar characteristics at presentation such as time interval from ingestion to presentation to the ED and the amount of organophosphate ingested, the dichlorvos group had significantly lower BChE levels than the fenitrothion group and lower RBC cholinesterase activity than the EPN group. Patients poisoned with EPN or dichlorvos had significantly higher inhibition of BChE activities from baseline than RBC AChE activities at presentation. Twenty four hours after administration of pralidoxime, RBC AChE activities had increased in patients in the dichlorvos and EPN groups, while RBC AChE activities had slightly decreased in the fenitrothion group. BChE activities increased significantly in the dichlorvos group but decreased in the EPN group. The recovery patterns of RBC AChE and BChE activities did not match in any particular individual. This study showed that the patterns of inhibition and recovery of the activities of two cholinesterases after treatment are highly variable according to the organophosphate and in different individuals.

RBC acetyl cholinesterase: A poor man's early diagnostic biomarker for familial alzheimer's and Parkinson's disease dementia.

Objective:Analysis of red blood cell acetyl cholinesterase (AChE) in a familial Alzheimer's diseases (AD) Parkinson's disease dementia (PDD) and their first generation.Setting:General hospital, Mahad district, Raigad.Patients and Methods:Clinically diagnosed patients of AD and PDD and their asymptomatic relatives. Their blood was collected in EDTA tube and transferred to laboratory at Mumbai.Result:Median red blood cell (RBC) cholinesterase levels amongst PDD, their first generation asymptomatic relatives, familial AD, asymptomatic relatives of AD, healthy controls, farmers exposed to pesticides (positive control) and other neurological condition without dementia (hypertension with TIA 1, sub-dural hematoma 2, hypothyroid 1, non-familial unilateral parkinsonism without dementia 3, writers cramps 2, hyponitremia 1 and cerebral palsy with non-fluent aphasia 1). Median values of RBC AChE were 19086.78 U/L, 15666.05 U/L, 9013.11 U/L, 7806.19 U/L, 14334.57 U/L, 9785.05 U/L and 13162.60 U/L, respectively. As compared to controls, RBC AChE levels were statistically significant among PDD (P = 0.004) and significantly lowered among familial AD patients (P = 0.010), relatives of patients (P = 0.010).Interpretations:Below the normal RBC AChE level is a potential biomarker in asymptomatic relatives of familial AD patients. RBC AChE is raised than normal level in patients suffering from PDD, where AChE inhibitors are helpful. However, RBC AChE level below the normal where AChE inhibitor may not be effective.

Derivation of human Biomonitoring Guidance Values for chlorpyrifos using a physiologically based pharmacokinetic and pharmacodynamic model of cholinesterase inhibition

A number of biomonitoring surveys have been performed for chlorpyrifos (CPF) and its metabolite (3,5,6-trichloro-2-pyridinol, TCPy); however, there is no available guidance on how to interpret these data in a health risk assessment context. To address this gap, Biomonitoring Guidance Values (BGVs) are developed using a physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model. The PBPK/PD model is used to predict the impact of age and human variability on the relationship between an early marker of cholinesterase (ChE) inhibition in the peripheral and central nervous systems [10% red blood cell (RBC) ChE inhibition] and levels of systemic biomarkers. Since the PBPK/PD model characterizes variation of sensitivity to CPF in humans, interspecies and intraspecies uncertainty factors are not needed. Derived BGVs represent the concentration of blood CPF and urinary TCPy associated with 95% of the population having less than or equal to 10% RBC ChE inhibition. Blood BGV values for CPF in adults and infants are 6100ng/L and 4200ng/L, respectively. Urinary TCPy BGVs for adults and infants are 2100μg/L and 520μg/L, respectively. The reported biomonitoring data are more than 150-fold lower than the BGVs suggesting that current US population exposures to CPF are well below levels associated with any adverse health effect.

Physiological and neurobehavioral effects of cholinesterase inhibition in healthy adults

IntroductionBased on common pharmacodynamic mechanisms, recent efforts to develop second generation alternatives for organophosphate (OP) prophylaxis have expanded to include cholinesterase (ChE) inhibiting compounds traditionally approved for use in the treatment of Alzheimer’s disease (AD). The primary purpose of this study was to determine the extent to which low-dose huperzine A, galantamine, or donepezil selectively inhibited acetylcholinesterase (AChE) versus butyrylcholinesterase (BChE) activity in healthy adults and whether such inhibition impacted neurobehavioral performance. MethodsIn addition to hourly red blood cell cholinesterase sampling, neurobehavioral function was assessed before and after a single oral dose of huperzine A (100 or 200μg), galantamine (4 or 8mg), donepezil (2.5 or 5mg), or placebo (n=12 subjects per drug/dose). ResultsCompared to placebo, both dosages of huperzine A and galantamine inhibited circulating AChE but not BChE. With the exception of huperzine A (200μg), which maintained declarative recall performance across sessions, compounds did not improve neurobehavioral performance. Some aspects of neurobehavioral performance correlated with AChE activity, although associations may have reflected time of day effects. DiscussionAlthough huperzine A and galantamine significantly inhibited AChE (and likely increased central acetylcholine levels), neither compound improved neurobehavioral performance. The latter was likely due to ceiling effects in this young, healthy test population. Under conditions of reduced cholinergic activity (e.g., Alzheimer's disease), AChE inhibition (and corresponding maintenance of cholinergic tone) could potentially maintain/augment some aspects of neurobehavioral function.

A human life-stage physiologically based pharmacokinetic and pharmacodynamic model for chlorpyrifos: Development and validation

Sensitivity to some chemicals in animals and humans are known to vary with age. Age-related changes in sensitivity to chlorpyrifos have been reported in animal models. A life-stage physiologically based pharmacokinetic and pharmacodynamic (PBPK/PD) model was developed to predict disposition of chlorpyrifos and its metabolites, chlorpyrifos-oxon (the ultimate toxicant) and 3,5,6-trichloro-2-pyridinol (TCPy), as well as B-esterase inhibition by chlorpyrifos-oxon in humans. In this model, previously measured age-dependent metabolism of chlorpyrifos and chlorpyrifos-oxon were integrated into age-related descriptions of human anatomy and physiology. The life-stage PBPK/PD model was calibrated and tested against controlled adult human exposure studies. Simulations suggest age-dependent pharmacokinetics and response may exist. At oral doses ⩾0.6mg/kg of chlorpyrifos (100- to 1000-fold higher than environmental exposure levels), 6months old children are predicted to have higher levels of chlorpyrifos-oxon in blood and higher levels of red blood cell cholinesterase inhibition compared to adults from equivalent doses. At lower doses more relevant to environmental exposures, simulations predict that adults will have slightly higher levels of chlorpyrifos-oxon in blood and greater cholinesterase inhibition. This model provides a computational framework for age-comparative simulations that can be utilized to predict chlorpyrifos disposition and biological response over various postnatal life stages.

Pesticide Exposure in Children

Pesticides are a collective term for a wide array of chemicals intended to kill unwanted insects, plants, molds, and rodents. Food, water, and treatment in the home, yard, and school are all potential sources of children's exposure. Exposures to pesticides may be overt or subacute, and effects range from acute to chronic toxicity. In 2008, pesticides were the ninth most common substance reported to poison control centers, and approximately 45% of all reports of pesticide poisoning were for children. Organophosphate and carbamate poisoning are perhaps the most widely known acute poisoning syndromes, can be diagnosed by depressed red blood cell cholinesterase levels, and have available antidotal therapy. However, numerous other pesticides that may cause acute toxicity, such as pyrethroid and neonicotinoid insecticides, herbicides, fungicides, and rodenticides, also have specific toxic effects; recognition of these effects may help identify acute exposures. Evidence is increasingly emerging about chronic health implications from both acute and chronic exposure. A growing body of epidemiological evidence demonstrates associations between parental use of pesticides, particularly insecticides, with acute lymphocytic leukemia and brain tumors. Prenatal, household, and occupational exposures (maternal and paternal) appear to be the largest risks. Prospective cohort studies link early-life exposure to organophosphates and organochlorine pesticides (primarily DDT) with adverse effects on neurodevelopment and behavior. Among the findings associated with increased pesticide levels are poorer mental development by using the Bayley index and increased scores on measures assessing pervasive developmental disorder, inattention, and attention-deficit/hyperactivity disorder. Related animal toxicology studies provide supportive biological plausibility for these findings. Additional data suggest that there may also be an association between parental pesticide use and adverse birth outcomes including physical birth defects, low birth weight, and fetal death, although the data are less robust than for cancer and neurodevelopmental effects. Children's exposures to pesticides should be limited as much as possible.

Monocrotophos poisoning through contaminated millet flour

Several episodes of mass poisoning by organophosphates (OPs) have been reported from the developing countries. The diagnosis of OP-poisoning is mainly based on the characteristic clinical features and history of exposure to a known OP compound. Estimation of serum and red blood cell (RBC) cholinesterase activities are helpful in confirming the diagnosis. However, there is controversy regarding a definite relationship between serum cholinesterase activity and the severity of clinical manifestations and prognosis. This report describes an episode of mass monocrotophos poisoning that occurred due to accidental ingestion of monocrotophos-contaminated millet (so-called bavta) flour involving eight severely poisoned persons. Clinical presentation included severe abdominal pain, diarrhoea, vomiting, pupil narrowing, and difficulty breathing. On hospital admission, plasma cholinesterase (PChE) and especially RBC acetylcholinesterase (AChE) activities correlated well with clinical symptoms presented by the patients. This case study highlights the need for clinicians to be aware of OP-pesticide poisoning from food sources and the need to look for depressed PChE and AChE activities that may point to OP exposure, so that OP-poisoning can be identified immediately and patients can receive specific treatment, rather than general treatment for food poisoning.

Effect of aqueous extract of Crocus sativus L. (saffron) stigma against subacute effect of diazinon on specific biomarkers in rats

In this study, the effect of aqueous extract of Crocus sativus L. (saffron) stigma was studied against subacute toxicity of diazinon (DZN) on specific biochemical markers in rats. Vitamin E (200 IU/kg) and the aqueous extract of saffron at doses 50, 100 and 200 mg/kg were injected intraperitoneally three times per week alone or with DZN (20 mg/kg/day, orally) for 4 weeks. Red blood cell (RBC) cholinesterase activity was inhibited by DZN and this effect was not affected by vitamin E or saffron plus DZN. The levels of serum tumor necrosis factor-α (inflammation marker), direct 8-iso-prostaglandin F(2α) (oxidative stress marker) and soluble protein-100 β (S100β, neuronal damage marker) were increased significantly by DZN. The saffron extract inhibited the effect of DZN on these biomarkers levels. However, vitamin E was able to only reduce 8-iso-prostaglandin F(2α) and S100β levels. This study showed that the aqueous extract of saffron prevents DZN-induced rise of several specific inflammation, oxidative stress and neuronal damage biomarkers.

Impact of Chemical Proportions on the Acute Neurotoxicity of a Mixture of Seven Carbamates in Preweanling and Adult Rats

Statistical design and environmental relevance are important aspects of studies of chemical mixtures, such as pesticides. We used a dose-additivity model to test experimentally the default assumptions of dose additivity for two mixtures of seven N-methylcarbamates (carbaryl, carbofuran, formetanate, methomyl, methiocarb, oxamyl, and propoxur). The best-fitting models were selected for the single-chemical dose-response data and used to develop a combined prediction model, which was then compared with the experimental mixture data. We evaluated behavioral (motor activity) and cholinesterase (ChE)-inhibitory (brain, red blood cells) outcomes at the time of peak acute effects following oral gavage in adult and preweanling (17 days old) Long-Evans male rats. The mixtures varied only in their mixing ratios. In the relative potency mixture, proportions of each carbamate were set at equitoxic component doses. A California environmental mixture was based on the 2005 sales of each carbamate in California. In adult rats, the relative potency mixture showed dose additivity for red blood cell ChE and motor activity, and brain ChE inhibition showed a modest greater-than additive (synergistic) response, but only at a middle dose. In rat pups, the relative potency mixture was either dose-additive (brain ChE inhibition, motor activity) or slightly less-than additive (red blood cell ChE inhibition). On the other hand, at both ages, the environmental mixture showed greater-than additive responses on all three endpoints, with significant deviations from predicted at most to all doses tested. Thus, we observed different interactive properties for different mixing ratios of these chemicals. These approaches for studying pesticide mixtures can improve evaluations of potential toxicity under varying experimental conditions that may mimic human exposures.

Comparison of the Ability of Pyridinium Aldoximes to Reactivate Human Red Blood Cell Acetylcholinesterases Inhibited by ethyl- and methyl-paraoxon

Oximes are acetylcholinesterase reactivators of use in poisoning with organophosphorus inhibitors of cholinesterase (OPIChE: (organophosphates and organophosphonates). They are clinically used as an adjunct to atropine in such exposure. Clinical experience with oximes is, however, disappointing. This paper reviews available data concerning the ability of established and new oximes to reactivate cholinesterases inhibited by two differently substituted prototypical organophosphates: ethyl- and methyl-paraoxon. The intrinsic toxicity of oximes is quantified in vitro by measuring the concentration required to inhibit red blood cell (RBC) cholinesterase activity by 50% (IC50). Reactivation ability is assessed in vitro via the IC50 shift graph. The slope of the shift graph (tan α) is used to quantify the magnitude of the protective effect (nM IC50 increase per µM reactivator). The ranking of reactivating potencies of the examined oximes determined with methyl-paraoxon as an inhibitor is essentially the same as the ranking obtained using ethyl-paraoxon as an inhibitor. In the in vitro model used, the presence of ethyl versus methyl substituents does not seem to significantly alter the ability of the examined oximes to reactivate the esterase. In vitro derived results were subsequently validated in vivo in rats using ethyl-paraoxon and methyl-paraoxon as cholinesterase inhibitors and various oximes as reactivators. Mortality data were compared and hazard ratios calculated using Cox proportional hazards model. Overall, the ability of in vitro testing (tan α determinations) to predict in vivo protection by oximes is limited. Keywords: Cholinesterase, DFP, Ethyl-paraoxon, Methyl-paraoxon, Organophosphate, Oxime, Treatment, benzodiazepines, oral pyridostigmine, organophosphorus

Assessment of exposure to sarin in military veterans at Porton Down

ObjectivesMortality and cancer incidence was recently examined in a cohort of >18 000 veterans of tests at Porton Down, 1941–89. Here we describe exposures to the nerve agent, sarin, and...

Transdermal delivery of physostigmine. A pretreatment against organophosphate poisoning.

Physostigmine absorption through isolated human skin and inhibition of plasma and red blood cell cholinesterases in guinea-pigs have been measured to assess the feasibility of its transdermal delivery as a pretreatment for organophosphate poisoning. Penetration of radiolabelled physostigmine across human epidermis was measured in-vitro using glass diffusion cells and optimization of physostigmine delivery was achieved by changes in vehicle formulation and use of penetration enhancers. Two-component vehicles consisting of propionic acid/isopropyl myristate (50:50) and propionic acid/oleic acid (50:50) produced the highest transdermal delivery of physostigmine. A comparison of formulations containing propionic acid alone with propionic acid plus oleic acid when applied to guinea-pigs, showed that inclusion of oleic acid allowed the amount of physostigmine and the size of the transdermal patch to be substantially reduced, whilst maintaining effective delivery rates. The formulation containing oleic acid was not irritant to guinea-pigs when applied to the skin for 48 h. It is concluded that a mixture of propionic acid and oleic acid containing physostigmine is a good candidate for transdermal delivery of physostigmine as a pretreatment for organophosphate poisoning.

Carbamoylated Enzyme Reversal as a Means of Predicting Pyridostigmine Protection Against Soman

The inhibition of human and mammalian red blood cell (RBC) cholinesterase (AChE) in whole blood in the presence of added pyridostigmine has been examined. After the addition of pyridostigmine to animal and human blood, red cells were separated from plasma at varying intervals and their enzyme activity measured. An apparent rate constant (ke) was derived for the reaction sequence in which carbamate is released from AChE inhibited by pyridostigmine. The constant is a complex of the rates of decarbamoylation and reinhibition of AChE in the blood sample. Rate constants were also determined for the spontaneous reactivation (ks) of carbamoylated AChE in the species studied. Values of Ks were greater than Ke in corresponding species but varied little between species. Pretreatment of animals with pyridostigmine is known to be an effective therapy against organophosphorus compounds, including soman. The ranking of ke values in mammalian blood was the same as that for the protection against soman in animals: monkey greater than guinea-pig greater than rabbit greater than rat (ke = 0.15, 0.07, 0.05, 0.02 h-1, respectively). Since ke for human blood (0.20 h-1) was greater than that of monkey, pyridostigmine pretreatment would be expected to be an effective prophylaxis for soman in humans.