Plasma Cholinesterase Activity Research Articles

Prediction of Pralidoxime Dose in Patients with Organophosphate Poisoning Using Machine Learning Techniques

Background: Early and appropriate antidotal therapy is crucial for patients with organophosphate poisoning. Objectives: Given the lack of a comprehensive consensus on the optimal dose of pralidoxime for patients with organophosphate poisoning, this study aims to develop a machine learning-based prediction model to determine the individualized pralidoxime dose for these patients. Methods: The dataset was divided into training and test sets with a 70:30 ratio. Feature selection was conducted using Pearson’s correlation coefficient (filter approach) method. Both classification and regression were employed to develop the prediction model using the selected features. The performance of the developed models was evaluated using ten-fold cross-validation and various metrics, including sensitivity, specificity, accuracy, F1-score, and AUC. The models were implemented and assessed using the scikit-learn library in Python. Results: After applying exclusion criteria, data from 325 patients were utilized to train and test the machine-learning models. In the classification approach, the random forest method achieved superior performance with an AUC of 98.6. In the regression approach, the gradient boosting regressor, with an R2 value of 65.4, outperformed other algorithms. Feature selection revealed that muscular weakness, plasma cholinesterase activity, and blood urea nitrogen were the most significant predictors of pralidoxime dose in the classification model. In the regression model, the top predictors were age, HCO3-VBG, and atropine bolus. Many of the selected features coincide with those identified in previous studies, with muscular weakness being particularly significant in both models. Conclusions: The most effective algorithms could be employed to develop a clinical decision support system for personalized pralidoxime dosage prediction in patients with organophosphorus poisoning. However, the study is constrained by its small sample size, retrospective design, and the absence of an external validation cohort. Conducting a prospective multicenter study with a larger sample size is crucial to validate the findings of this study.

The role of mivacurium in contemporary anesthesiology: a narrative review

Background: Mivacurium is the shortest-acting non-depolarizing neuromuscular blocking agent (NMBA) with a rapid onset of action that is mainly used for short procedures. Despite the fact that mivacurium has a very favorable average 6-minute recovery index after its infusion in comparison to the approximately 15–30 minutes for atracurium, mivacurium is still not really popular among practicing anesthesiologists. Many new studies showing the potential further benefits of implementing mivacurium into daily practice are still being published. Aim of the Study: This study aimed to focus on spreading the common knowledge about the detailed pharmacokinetic and pharmacodynamic properties of mivacurium as a medication that has yet to be used widely by practicing anesthesiologists. Material and methods: The literature review was conducted using the common sources of original articles such as PubMed and Google Scholar from 1975 to September 2022. Results: Based on the literature review, we observed that Mivacurium at a dosage of 6μg produces a lower impact on hemodynamics, shorter intubation and extubation times, faster postoperative recovery, absence of the accumulation of neuromuscular blockade, higher safety, and no significant increase in allergic related adverse events in comparison with other NMBAs.Conclusions: Mivacurium is a muscle relaxant medication that is particularly suited for short-lasting surgical procedures. However, it is important to remember that existing mutations in the butyrylcholinesterase enzyme (BChE) may prolong the effect of the neuromuscular blockade due to significantly reducing plasma cholinesterase activity. Therefore, it is advised to stay cautious during its use as more research needs to be done to be able to thoroughly assess the potential advantages and disadvantages of mivacurium introduction in particular patients

Rationally Designed Functionalization of Single-Walled Carbon Nanotubes for Real-Time Monitoring of Cholinesterase Activity and Inhibition in Plasma.

Enzymes play a pivotal role in regulating numerous bodily functions. Thus, there is a growing need for developing sensors enabling real-time monitoring of enzymatic activity and inhibition. The activity and inhibition of cholinesterase (CHE) enzymes in blood plasma are fluorometrically monitored using near-infrared (NIR) fluorescent single-walled carbon nanotubes (SWCNTs) as probes, strategically functionalized with myristoylcholine (MC)- the substrate of CHE. A significant decrease in the fluorescence intensity of MC-suspended SWCNTs upon interaction with CHE is observed, attributed to the hydrolysis of the MC corona phase of the SWCNTs by CHE. Complementary measurements for quantifying choline, the product of MC hydrolysis, reveal a correlation between the fluorescence intensity decrease and the amount of released choline, rendering the SWCNTs optical sensors with real-time feedback in the NIR biologically transparent spectral range. Moreover, when synthetic and naturally abundant inhibitors inhibit the CHE enzymes present in blood plasma, no significant modulations of the MC-SWCNT fluorescence are observed, allowing effective detection of CHE inhibition. The rationally designed SWCNT sensors platform for monitoring of enzymatic activity and inhibition in clinically relevant samples is envisioned to not only advance the field of clinical diagnostics but also deepen further understanding of enzyme-related processes in complex biological fluids.

In vitro Effects of Propofol and Bupivacaine on Pregnant Women’s Plasma Cholinesterase Activity and Malondialdehyde Level

Background: Propofol and bupivacaine are commonly used anesthetics for cesarean section (CS), and they might modulate plasma cholinesterase (ChE) activity and oxidative stress during the last stage of pregnancy. This study aimed to assess the in vitro effects of propofol and bupivacaine on plasma ChE activity and malondialdehyde (MDA) levels in pregnant women before undergoing elective CS. Methods: The plasma samples of 20 women set for elective CS were pooled for the in vitro determination of the effects of propofol and bupivacaine separately on plasma ChE activity (10 minutes of incubation with different concentrations at 37ºC) and the MDA level after the in vitro exposure of plasma samples containing different anesthetic concentrations to H2O2 (100 µM, incubated for 1 hour at 37ºC). Results: Bupivacaine at 1.1 and 2.2 µM significantly inhibited plasma ChE in vitro in a concentration-dependent manner by 13% and 20%, respectively. Propofol at 25 and 50 µM did not affect plasma ChE. A unique finding in this study was that both propofol and bupivacaine revealed an antioxidant effect, as both propofol at concentrations of 25, 50, and 100 µM and bupivacaine at 1.1, 2.2, and 4.4 µM reduced the MDA level in a concentration-dependent manner in vitro after the incubation of plasma samples with H2O2 as a source of oxidant. Conclusions: The in vitro findings suggest that bupivacaine exerts anti-ChE activity that should be taken into consideration in CS anesthesia, and both propofol and bupivacaine possess antioxidant properties that need additional clinical studies.

Adverse neurobehavioral changes with reduced blood and brain cholinesterase activities in mice treated with statins.

Pleiotropic effects of hypolipidemic statins with behavioral outcomes have been suggested in humans and laboratory animals. There is limited information on the neurobehavioral effects of statins in mice. The aim of the present study was to examine changes in neurobehavioral performance and cholinesterase (ChE) activity in mice after high doses of three commonly used statins (atorvastatin, simvastatin, and rosuvastatin). Two hours after vehicle (control) or statin dosing at 250, 500, 750, or 1000 mg/kg orally, each mouse was subjected to 5 min open-field activity, negative geotaxis at an angle of 45°/60 s, 5 min head pocking, and forced swimming endurance. Plasma, erythrocyte, and brain ChE activities were determined spectrophotometrically 2 and 24 h after oral dosing of statins at 500 and 1000 mg/kg. The statins variably, but dose-dependently and significantly (p < 0.05) delayed the latency to move in the open-field arena, decreased locomotion and rearing, reduced head pocking, and delayed negative geotaxis performance. However, statins significantly increased the duration of forced swimming and decreased the duration of immobility in the swimming tank. Statins significantly and dose-dependently decreased plasma, erythrocyte, and brain ChE activity 2 and 24 h after dosing. Plasma and brain ChE activities recovered by 5%-32.9% and 5.7%-14.4% 24 h later from the 2 h ChE values, respectively. High doses of statins differentially modulate neurobehavioral outcomes in mice in association with reduced plasma, erythrocyte, and brain ChE activity. Plasma or erythrocyte ChE may be used for biomonitoring of the adverse/therapeutic effects of statins.

Plasma Cholinesterase Activity in Patients With Rheumatoid Arthritis and Toxoplasmosis.

Background and objective Rheumatoid arthritis (RA) is a chronic autoimmune disease causing synovium inflammation and functional impairment. Toxoplasmosis is an intracellular zoonotic parasitic infection anda risk factor in immunosuppressed diseases including RA. The involvement of the cholinergic mechanism is not clear when both diseases exist in combination. This study aimed to examine plasma cholinesterase (ChE) activity in patients suffering from RA with concomitant toxoplasmosis, taking into account the enzyme susceptibility to in vitro inhibitory challenge with the organophosphate dichlorvos in RA patients. Methods This was a case-control study involving 88 RA patients and 61 healthy controls of both genders.The RA patients were allocated into three groups. The first group received no therapy (n=14), the second group received conventional anti-arthritis therapy (n=49), and the third group received conventional+biologic therapy(n=25). Plasma ChE activity was determined by an electrometric method. Plasma samples were screened for Toxoplasmagondii (T. gondii)infection, using ELISAT. gondii antibodies IgG andIgM.In vitro inhibition of plasma ChE activitywas assessed by incubating the samples with dichlorvos at0.25 and 0.5 μM.The time-dependent dichlorvos (0.25 μM)-induced plasma ChE inhibition and its kinetics weredetermined. Results The RA patients comprised 76 (86.4%) females and 12 males (13.6%), whereas healthy controls included 22 (36.1%) females and 39 (63.9%) males. The rates of toxoplasmosis IgG positivity in controls and RA patients were 26.2% and 39.8%, respectively. Plasma ChE activity in patients with RA was significantly higher than that in the control group, by 16%. Plasma ChE values of RA patients with conventional therapy and conventional + biologic therapy were higher than that of the control group, by 18% and 27%, respectively. Odds and risk ratios of elevated plasma ChE activity (20%) in RA patients with therapyindicated that high plasma ChE activity among RA patients with therapyis a risk factor. The plasma ChE activity of T. gondii IgG-positive RA patients was not significantly different from that of theIgG-negative ones. Dichlorvos at 0.25 and 0.5 μM significantly inhibited in vitro plasma ChE activity incontrols and RA patients. The rates of plasma ChE inhibition by dichlorvos were lower in the RA groups with conventional therapyin comparison with those in the control group (77% vs. 91%). Examining the dichlorvos time-dependent ChE inhibition kinetics, RA groups showed increases in the half-life of inhibition by 23.6% to 32.7% and the total inhibition time by 23.5% to 32.5%, together with decreases in the inhibition rate constant by 19% to 24.5%, an indication of reduced inhibition rate of plasma ChE activity compared to that of the control group. Conclusions The autoimmune nature of RA and its chronicity might have contributed to the increase in plasma ChE activity among the patients. This increase in enzyme activity could be a risk factor in RA patients undergoing conventional therapy alone or in combination with biologic therapy; however, the clinical significance of such a condition remains obscure at present. The in vitro inhibition of plasma ChE activity in RA patients suggests reduced susceptibility of the enzyme to ChE inhibition by dichlorvos. Toxoplasmosis was not a risk factor when plasma ChE activity was taken into account among RA patients.

Association of Reduced Maternal Plasma Cholinesterase Activity With Preeclampsia: A Meta-Analysis.

Blood butyrylcholinesterase (BChE) activity has been found to decrease during pregnancy and reportedly decrease even more in preeclampsia (PE). The purpose of the present meta-analysis was to answer a specific question of whether BChE activity (in the plasma, serum, or whole blood) is reduced in pregnant women suffering from PE compared to those with normal pregnancy. The meta-analysis included 15 studies with 20 records of BChE activity in 608 women compared to 569 healthy pregnant (control) ones. The studies were subjected to quality assessment using the Newcastle-Ottawa Scale (NOS). Using the Meta-Essentials software program 1.5, the one-group random effects model and forest plot revealed that the percentage of BChE activity in pregnant women with PE was 84.84% of the control value, with a standard error of 4.09 and 95% C.I. of 76.28, 93.41, indicating a significant 15.16% reduction in BChE activity in comparison to healthy pregnancy. No significant heterogeneity was seen in the analyzed data and the funnel plot did show publication bias. Subgroup (mild, severe, and unclassified PE) forest plot analysis revealed that the % BChE activities in PE compared to respective healthy pregnancies were 96.28%, 97.08%, and 76.62%, respectively with no heterogeneity. The median NOS score of the 15 studies included in the meta-analysis was 7, ranging from 5 to 8 (medium to high quality), and the forest plot showed an effect size of 0.735. This meta-analysis shows that BChE activity is reduced in PE compared with normal pregnancyand its value as a biomarker warrants further clinical studies.

The Influence of Exposure to Pesticides on Plasma Cholinesterase Levels and Hepatic, and Renal Functions among Farmers in Khan Yunis Governorate, Palestine

Background: An increase in acute intoxication signs/symptoms indicates a serious public health problem among farmers who use organophosphate (OP) pesticides. This study aimed to assess the health effects of OP pesticides on farm workers who deal with pesticides in Khan Yunis Governorate, Palestine. Methods: A comparative cross-sectional study started in March and finished in September 2021 on a total of 120 randomly selected farmers, out of them 60 subjects that used pesticides (cases group) for six months or more. The other 60 were not exposed to pesticides (controls group), aged between 20-50 years old. Sociodemographic data, health-related data, and working-related data habits of the study population were taken by interview questionnaire. Biochemical evaluations were carried out. Collected data were analyzed using SPSS 22. Results: The prevalence of abnormal plasma cholinesterase (PChE) activity among the cases group due to chemical poisoning was significantly higher as compared to those in the control group (p ≤ 0.05). The case group has higher levels of serum liver enzymes (AST, ALT, &amp; ALP) when compared with the control group (p ≤ 0.05 for all). The kidney function indicators (creatinine and urea) were significantly higher among the cases group as compared to the control group (p ≤ 0.05 for all). The occurrence of headaches is associated with abnormal PCHE activity among farmers who on pesticides. Conclusion: The decrease in PCHE activity and increase in serum AST, ALT, ALP, urea &amp; creatinine that were observed among farmers who were on pesticides-using in the current study indicate the adverse and toxic effects of pesticides on the liver and kidney functions among them, so these observations should be of interest to health and environmental policymakers in Palestine.

Simple and rapid colorimetric method for determination of erythrocyte and plasma cholinesterase activities and comparison with the standard Ellman’s method

Simple and rapid colorimetric method for determination of erythrocyte and plasma cholinesterase activities and comparison with the standard Ellman’s method

Differential effects of statins on plasma and brain cholinesterase activities in chicks

Statins used to treat dyslipidemia may differentially modulate cholinesterase (ChE) activity impacting neuronal function. This study examines the effects of three statins (atorvastatin, fluvastatin, and simvastatin) on plasma and brain ChE activities and cholesterol levels in a chick model of 7-14 days old. Chicks were dosed orally with single doses of each statin at 50, 100, and 200mg/kg or repeated doses at 100mg/kg/day for 14 consecutive days. Plasma and whole brain ChE activities were measured electrometrically, whereas cholesterol levels were measured using a commercial colourimetric kit. In vitro ChE inhibition by the statins was initiated at 37°C for 10 mins. Data were statistically analysed using analysis of variance followed by the least significant difference test. Atorvastatin and fluvastatin did not significantly affect plasma ChE activities 2 hours after the oral administration, whereas simvastatin at 100 and 200mg/kg significantly increased (28% and 16%, respectively) plasma ChE activity. Repeated oral doses of the statins did not significantly affect plasma ChE activity. However, only simvastatin significantly decreased whole brain ChE activity by 33%. Repeated treatments with the three statins significantly reduced cholesterol levels in the plasma but not in the whole brain. The three statins inhibited in vitro plasma and whole brain ChE activities by 10-33% and 8-43%, respectively. The results suggested that the statins differentially modulated ChE activity in vivo and in vitro in chicks. Additional in vivo studies are warranted on statin effects on ChE activity in different brain regions of animal models.

Lack of cholinergic features in healthcare workers caring for a patient with organophosphate poisoning

Introduction Controversy exists with regard to risk of secondary exposure of health care workers caring for patients who have ingested an organophosphate insecticide. We aim to report clinical effects of staff members caring for an organophosphate poisoned patient. Incident A 76-year-old male presented to the Emergency Department exhibiting a cholinergic toxidrome requiring atropine, intubation and mechanical ventilation. Methods We undertook a retrospective chart review of any Emergency Department presentations for medical assessment in relation to the incident and conducted telephone interviews of any healthcare workers who did not present but were deemed to be closely involved with patient care. We collected data including age, gender, symptoms reported and plasma cholinesterase activity measurement. Results We collected data from 13 individuals, of whom nine presented for medical assessment, including the patient’s spouse. Five additional staff members were interviewed, having been identified via Emergency Department rostering documentation. The 13 healthcare workers comprised five nurses, four paramedics and four doctors. Dizziness and nausea were reported in two and the patient’s spouse reported one episode of vomiting. Of the nine patients who had plasma cholinesterase activity measured, none were below the laboratory reference range, including those who experienced symptoms. Conclusions We found no clinical nor biochemical evidence of toxicity in healthcare workers caring for a critically ill patient with organophosphate ingestion. These findings are consistent with previously published guidelines advocating standard/Level D personal protective equipment. We believe that emergency departments should not be closed as a safety measure.

Occupational Evaluation of Federal Highway Police Officers Exposed to Cholinesterase Inhibiting Insecticides.

The aim of this study is to evaluate the effects of occupational exposure of federal highway police (PRF) officers to cholinesterase-inhibiting insecticides. We evaluate erythrocyte and plasma cholinesterase activity, pulse rate, systolic and diastolic pressure, and clinical evaluation through the Mini-Mental State Examination and the Diagnostic and Statistical Manual of Mental Disorders , Fifth Edition . All PRF officers evaluated were male, between 22 and 49 years of age. Pulse rate of the subjects were statistically superior in the post-exposure moment when compared with pre-exposure moment. Inhibition of acetylcholinesterase and butyrylcholinesterase was significant in the post-exposure moment when compared with pre-exposure moment. The results of the present work show that there are significant biochemical changes, which can be the beginning of serious deleterious effects to the health of PRF officers.

Changes in blood oxidative stress biomarker and cholinesterase activity after general vs spinal anesthesia for elective cesarean sections

Background &amp; Objective: There is an increased ratio of cesarean sections (CS) compared to normal deliveries the world over. Both general and regional anesthetic techniques are in practice for CS. Limited information is available on the determination of blood cholinesterase (ChE) activity in conjunction with oxidative stress biomarkers after the CS. The purpose of the present study was to determine and compare the plasma and erythrocyte ChE activity as well as malondialdehyde (MDA) level and total antioxidant status in pregnant women before anesthesia and after the use of general anesthesia (GA) or spinal anesthesia (SA) for elective CS.&#x0D; Methodology: A pre-post study was conducted on 102 full-term pregnant women, who underwent elective CS in four hospitals at Duhok (Iraq) from January 2022 to July 2022. GA with propofol and SA with bupivacaine 0.5% were administered to 52 and 50 women, respectively. Maternal blood samples before anesthesia and after the completion of operation were assayed for the ChE activity in the plasma and erythrocytes, and plasma oxidative stress biomarkers malondialdehyde and total antioxidant status.&#x0D; Results: Plasma ChE activity significantly decreased in the GA and SA groups after the cesarean-deliveries compared to the corresponding pre-anesthetic values. The plasma MDA level in both GA and SA groups, but not the total antioxidant status, was significantly reduced. Estimation of the odds ratio and the relative risk indicated that a risk factor is associated with the reduced plasma ChE activity in women after the CS when the general anesthetic propofol is used.&#x0D; Conclusion: Both general anesthesia with propofol and spinal anesthesia with bupivacaine inhibited plasma cholinesterase activity and reduced oxidative stress biomarker malondialdehyde after the cesarean sections.&#x0D; Abbreviations: CS - Cesarean section; ChE: Cholinesterase; EChE: Erythrocyte Cholinesterase; MDA: Malondialdehyde; OS: Oxidative Stress; PChE: Plasma ChE; TAS: Total Antioxidant Status.&#x0D; Key words: Anesthesia, Spinal; Cesarean section; General anesthesia; Malondialdehyde; Oxidative stress&#x0D; Citation: Karam RS, Mohammad FK. Changes in blood oxidative stress biomarker and cholinesterase activity after general vs spinal anesthesia for elective cesarean sections. Anaesth. pain intensive care 2023;27(3):396−404; DOI: 10.35975/apic.v27i3.2244&#x0D; Received: March 23, 2023; Reviewed: May 06, 2023; Accepted: May 09, 2023

In vitro Inhibition of Human Plasma and Erythrocyte Cholinesterases by a Selected Drugs (Enzymes Inhibitors)

The inhibitory effect for human plasma and erythrocyte cholinesterase activity by six drugs already known as an enzyme inhibitors (Cimetidine, Ciprofloxacin, Donepezil, Sildenafil, Erythromycin, and Chlorpheniramine) was tested in vitro. The affinity toward the cholinesterase system was evaluated by using different concentrations of the investigated drugs. The cholinesterase activities were determined by using the modified electrometric method. Each drug showed different ability to inhibit cholinesterase activity depending on its concentration and its selectivity to the either plasma or erythrocyte cholinesterase; only Donepezil and Chlorpheniramine showed higher inhibitory effect. Ciprofloxacin showed moderate inhibition of cholinesterase but still statistically insignificant. Cimetidine, Sildenafil and Erythromycin showed little inhibitory activity although they have a good inhibitory effect on the liver enzyme system Cytochrome P450 (CYP450 ).

Plasma cholinesterase activity: A benchmark for rapid detection of pesticide poisoning in an avian scavenger

Poisoning due to exposure to organophosphate and carbamate pesticides is a common threat for many wildlife species, especially for scavengers such as vultures. The Griffon vulture population (Gyps fulvus), for instance, is deteriorating in the Eastern Mediterranean, and is considered to be critically endangered in Israel, where 48 out of 107 (45 %) known injury/mortality cases in 2010–2021 were caused by poisoning. Lack of specific clinical indications, together with levels of organophosphate or carbamate pesticides too low to detect, challenge the ability to diagnose and treat such poisoning events. The activity of cholinesterase (ChE) in plasma has the potential to serve as an effective biomarker for monitoring exposure to anticholinesterase pesticides in live vultures. Yet, the applicability of this approach has been limited by intra- and inter-species variations in ChE basal levels. The present study aims to provide a benchmark for ChE activity levels in healthy Griffons and their intra-species variation. Blood samples from free-roaming (n = 231) and captive (n = 63) Griffons were collected during routine monitoring, and ChE levels were determined using a colorimetric method. We established that the ChE in the plasma of Griffons reflects mostly acetylcholinesterase as the dominant form. ChE levels in healthy Griffons are 0.601 ± 0.011 U/ml (mean ± SE), while Griffons with suspected or confirmed pesticide poisoning display much lower levels of ChE activity (typically <0.3 U/ml). We also characterized the age dependence of ChE activity, as well as differences among groups from different locations or origins. Our study provides a rapid diagnostic tool for the detection of exposure to organophosphate and carbamate pesticides that should facilitate the lifesaving treatment and the conservation of this species. Moreover, our protocols can be adapted to other species and geographical areas, addressing pesticide poisoning worldwide and contributing to the protection of endangered species and their ecological functions (e.g. sanitation by scavengers).

The relation of autonomic biomarkers to the patient's outcome with acute coronary syndrome

Objectives: This study aimed to evaluate the neurohormonal activity in patients with acute coronary syndrome and their relation to clinical outcomes by measuring plasma chromogranin A and plasma and RBC cholinesterase activity. Methods: In this case-control study, cardiac and neurohormonal parameters were compared between fifty-one patients with acute coronary syndrome admitted to the cardiac center in Azadi teaching Hospital in Duhok-Iraq, and thirty comparable gender and age-healthy subjects. Results: A significant increase in sympathetic activity was reported in patients with the acute coronary syndrome, reflected by the rise in the plasma chromogranin A compared to the control group (994.47 vs. 1203.95 ng/L, respectively, P&lt;0.05). Meanwhile, cardiac troponin was significantly elevated in those patients compared to healthy subjects (0.17 vs. 4.82 ng/ml, respectively). However, the parasympathetic biomarkers (plasma and RBC cholinesterase activity) did not differ substantially between patients and healthy controls (0.83 vs. 0.92, P &gt; 0.05 and 1.36 vs. 1.37, P&gt;0.05, respectively). Serum troponin I was more valid than chromogranin A in differentiating acute coronary syndrome from healthy subjects. The area under the curve for troponin I was (0.989) compared to ( 0.724) for chromogranin A. Furthermore, plasma chromogranin A but not plasma and RBC cholinesterase activity was significantly increased in fatal cases compared to nonfatal patients (1166.68 vs. 3435.64 ng/L). Conclusion: Plasma chromogranin A was less effective than troponin I in detecting acute coronary cases; however, it can be helpful as a prognostic marker in those patients. Parasympathetic biomarkers were not appreciable in diagnosing and detecting risky patients.

Prediction of acute organophosphate poisoning severity using machine learning techniques

Poisoning with organophosphate compounds is a significant public health risk, especially in developing countries. Considering the importance of early and accurate prediction of organophosphate poisoning prognosis, the aim of this study was to develop a machine learning-based prediction model to predict the severity of organophosphate poisoning. The data of patients with organophosphate poisoning were retrospectively extracted and split into training and test sets in a ratio of 70:30. The feature selection was done by least absolute shrinkage and selection operator method. Selected features were fed into five machine learning techniques, including Histogram Boosting Gradient, eXtreme Gradient Boosting, K-Nearest Neighborhood, Support Vector Machine (SVM) (kernel = linear), and Random Forest. The Scikit-learn library in Python programming language was used to implement the models. Finally, the performance of developed models was measured using ten-fold cross-validation methods and some evaluation criteria with 95 % confidence intervals. A total of 1237 patients were used to train and test the machine learning models. According to the criteria determining severe organophosphate poisoning, 732 patients were assigned to group 1 (patients with mild to moderate poisoning) and 505 patients were assigned to group 2 (patients with severe poisoning). With an AUC value of 0.907 (95 % CI 0.89–0.92), the model developed using XGBoost outperformed other models. Feature importance evaluation found that venous blood gas-pH, white blood cells, and plasma cholinesterase activity were the top three variables that contribute the most to the prediction performance of the prognosis in patients with organophosphate poisoning. XGBoost model yield an accuracy of 90.1 % (95 % CI 0.891–0.918), specificity of 91.4 % (95 % CI 0.90–0.92), a sensitivity of 89.5 % (95 % CI 0.87–0.91), F-measure of 91.2 % (95 % CI 0.90–0.921), and Kappa statistic of 91.2 % (95 % CI 0.90–0.92). The machine learning-based prediction models can accurately predict the severity of organophosphate poisoning. Based on feature selection techniques, the most important predictors of organophosphate poisoning were VBG-pH, white blood cell count, plasma cholinesterase activity, VBG-BE, and age. The best algorithm with the highest predictive performance was the XGBoost classifier.

Occurrence of butyrylcholinesterase polymorphisms in patients undergoing surgery in Slovakia.

Post-operative residual curarization is a persisting problem, characterized by muscle fatigue, exhaustion or paresis, caused by the use of neuromuscular blocking agents with prolonged postoperative effect. Genetically, determined changes in cholinesterase activity can be a major reason for persistent muscle blockade after administration of muscle relaxants. Regarding the subsistence of polymorphisms in the plasma cholinesterase gene causing change in enzyme activity and metabolism of applied drugs, we investigated the frequency of two polymorphisms known to reduce its activity significantly in patients undergoing surgery. Primary results show a relatively high occurrence of plasma cholinesterase K risk allele (18.75%). Characterization of the lacking information about genetic background of changes in plasma cholinesterase activity within Slovakia may allow for easier decision-making in clinical practice when selecting alternative neuromuscular blocking and also reversal agents.

Blood cholinesterase activities and oxidative stress status among farmworkers using pesticides in Duhok, KRG, Iraq

Background: The use of pesticides by farmworkers poses considerable health risks. This study was undertaken to examine plasma and erythrocyte cholinesterase activities, plasma oxidative biomarkers malondialdehyde (MDA), and total antioxidant status (TAS) among farmworkers using different pesticide products in Duhok, northern of Iraq. Methods: This is a case-control study conducted between November 2021 to July 2022 on 92 male farmworkers who were exposed to pesticides in comparison with 44 non-exposed male subjects (control). The availability and uses of pesticides were obtained from 19 agrochemical shops and the farmworkers exposed to pesticides. Demographic data of pesticide-exposed farmworkers and their practice of pesticide applications were recorded. Plasma and erythrocyte cholinesterase activities and plasma MDA and TAS levels were determined in both groups. Results: The farmworkers had a significant 10.0% increase in plasma MDA level, with no significant changes in blood cholinesterase activities or the TAS level. Odds and risk ratios of reduced plasma cholinesterase activity (20.0%) suggested an association of health risks in pesticide-exposed farmworkers. Most of the pesticide products (278) in use were insecticides (47.0%), which comprised mainly 26.0% pyrethroids and 3.0-7.0% anticholinesterase insecticides, among others. The majority of the farmworkers (51%) were merely aware of the general target use of the pesticide, and 75% had an exposure history of &gt; 5 years. Pesticide application was mostly (50.0%) manual, and 54.0% used insufficient personal protection equipment; 32.0% ate and drank at work, 48.0% practiced disposal of empty pesticide containers by burning and/or burying them, whereas 25.0% dumped the containers indiscriminately, and 25% disposed them at garbage sites openly. Conclusion: The farmworkers, with only a marginal increase in oxidative stress biomarker MDA, did not suffer from significant reductions in blood cholinesterase activities, although odds and risk ratios of reduced plasma cholinesterase activity suggested a health risk. Implementation of a national program is needed to measure pre-exposure blood cholinesterase activities in farmworkers.

Recognition and Assessment of Antidotal Effects of Diphenhydramine against Acute Carbaryl Insecticide Poisoning in a Chick Model

Diphenhydramine antagonizes poisoning produced by cholinesterase (ChE) inhibiting insecticides. This study examines the effects of diphenhydramine against acute poisoning induced by the carbamate insecticide carbaryl in a chick model. The effects of diphenhydramine on the 24 h median Lethal Dose (LD50), and acute toxicity of carbaryl were assessed in chicks (7-15 days old). The plasma and whole brain ChE activities were measured electrometrically in vitro and in vivo. Diphenhydramine at 10mg/Kg Body wt. administered intramuscularly 15 min before carbaryl dosing increased the oral LD50 value of carbaryl (207 mg/Kg Body wt.) by 62%. Carbaryl at 250 mg/Kg Body wt. has orally produced toxidrome of cholinergic poisoning with 100% lethality in 24 h. Diphenhydramine (10mg/ Kg Body wt.) used 15 min before carbaryl (250mg/Kg Body wt., orally) was the most effective dose (vs 5 and 20mg/Kg Body wt.) in delaying carbaryl-toxicity and increasing survivals in chicks. The intramuscular median effective dose (ED50) of diphenhydramine which prevented 24 h carbaryl-death in chicks was 8.6mg/ Kg Body wt. The antidotal response to diphenhydramine was similar to that of the standard antidote atropine sulfate. Diphenhydramine at 10mg/Kg Body wt., given immediately after carbaryl (200mg/Kg Body wt.), reduced the percentages of plasma and whole brain ChE inhibitions in vivo by 12- and 13%, respectively. Carbaryl (10μmol/L) in vitro inhibited ChE activities in the plasma and brain by 53 and 77%, respectively; these inhibitions were reduced by 13- and 14%, respectively, when diphenhydramine (10μmol/L) was added to in vitro reactions. Diphenhydramine exerted antidotal action against a model of acute and lethal carbaryl intoxication in chicks.