Correlation of Pseudocholinesterase Level with Clinical, Biochemical Parameters Including Cardiac Profile and the Outcome in Organophosphorus Poisoning.

BACKGROUND: Poisoning is a significant health hazard and a leading cause of morbidity and mortality worldwide. India, being a predominantly agrarian country, routinely employs organophosphate (OP) pesticides in farming, and they are readily available "over the counter." OPs exert their toxicity by interfering with the normal function of acetylcholine, an essential neurotransmitter throughout the autonomic and central nervous systems. Due to the limited availability of facilities and resources in health-care systems, and economically restraining patients, it is necessary to rely more on clinical features to assess the severity of poisoning and manage the condition properly. METHODOLOGY: It was a hospital-based prospective observational study that included patients aged >13 years in a tertiary care hospital. All patients were clinically evaluated based on their history and examination. The diagnosis was made based on characteristic clinical manifestations or evidence of exposure to organophosphorus compounds (corroborative evidence such as empty containers and the odor of gastric aspirates). Clinical severity was assessed and categorized according to the Peradeniya Organophosphorus Poisoning Scale (POP scale). A score of 0-3 is considered mild poisoning, 4-7 as moderate poisoning, and 8-11 as severe poisoning. RESULTS: Out of the 50 patients enrolled in the study, 17 (34.00%) were aged <20 years, 19 (38%) were in the 20-30 years age group, and 14 (28%) were aged >30 years. Ingestion is the only mode of exposure to poisoning. None of the patients had history of contact or inhalational exposure. Of the 50 cases, 12 (24.0%) were in the mild category, 26 (52.0%) in the moderate category, and 12 (24%) in the severe category on the POP grading. A comparison of the mean serum pseudocholinesterase, troponin-T, and pro-BNP levels with severity was performed. In mild OP poisoning, the mean serum PChE level was 2766.58 ± 1120.44; in moderate, it was 1969.35 ± 1330.07, and in severe, it was 701.83 ± 961.17. Pseudocholinesterase levels decreased progressively with increasing clinical severity from mild-to-severe cases, and this association was statistically significant (P < 0.001). Two-dimensional echocardiography screening done in all patients did not show any significant abnormalities. CONCLUSION: This study shows that serum PCE is reduced in OP poisoning and correlates with the clinical severity grading done by the POP scale and is also associated with an increase in the duration of intensive care unit stay. No significant evidence of direct cardiac injury was observed in this study. A low Glasgow Coma Scale score and an increased respiratory rate at presentation are associated with poor outcomes.

Résumé Contexte:L'empoisonnement est un risque important pour la santé et une cause principale de morbidité et de mortalité dans le monde. L'Inde, étant principalement pays agraire, utilise régulièrement des pesticides organophosphotés (OP) dans l'agriculture, et ils sont facilement disponibles «en vente libre¼. OPS exerce leur toxicité en interférant avec la fonction normale de l'acétylcholine, un neurotransmetteur essentiel à travers l'autonomie et le centre systèmes nerveux. En raison de la disponibilité limitée des installations et des ressources dans les systèmes de soins de santé, et de la contention économique des patients, il est nécessaire pour s'appuyer davantage sur les caractéristiques cliniques pour évaluer la gravité de l'empoisonnement et gérer correctement la condition.Méthodologie:c'était un Étude d'observation prospective basée à l'hôpital qui comprenait des patients âgés de> 13 ans dans un hôpital de soins tertiaires. Tous les patients étaient cliniquement évalué en fonction de leur histoire et de leur examen. Le diagnostic a été posé sur la base de manifestations cliniques caractéristiques ou de preuves de Exposition aux composés organophosphores (preuves corroborantes telles que les conteneurs vides et l'odeur des aspirations gastriques). Gravité clinique a été évalué et classé selon l'échelle d'empoisonnement de Peradeniya organophosphorus (échelle pop). Un score de 0 à 3 est considéré comme doux Empoisonnement, 4­7 comme empoisonnement modéré et 8-11 comme empoisonnement sévère.Résultats:Sur les 50 patients inscrits à l'étude, 17 (34,00%) étaient âgés de <20 ans, 19 ans (38%) dans le groupe d'âge de 20 à 30 ans et 14 (28%) étaient âgés de> 30 ans. L'ingestion est le seul mode d'exposition à empoisonnement. Aucun des patients n'avait des antécédents de contact ou d'inhalation. Sur les 50 cas, 12 (24,0%) étaient dans la catégorie légère, 26 (52,0%) Dans la catégorie modérée, et 12 (24%) dans la catégorie sévère sur le classement POP. Une comparaison de la pseudocholinestérase sérique moyenne, Les niveaux de troponine - T et pro-BNP avec gravité ont été réalisés. Dans l'empoisonnement à l'op léger, le taux de PCHE sérique moyen était de 2766,58 ± 1120,44; dans Modéré, c'était 1969.35 ± 1330,07, et en sévère, il était de 701,83 ± 961,17. Les niveaux de pseudocholinestérase ont diminué progressivement avec l'augmentation Gravité clinique des cas légers à sévère, et cette association était statistiquement significative ( P <0,001). Échocardiographie bidimensionnelle Le dépistage effectué chez tous les patients n'a montré aucune anomalie significative.Conclusion:cette étude montre que le PCE sérique est réduit en op empoisonnement et corréler avec le classement de gravité clinique effectué par l'échelle POP et est également associé à une augmentation de la durée de séjour de l'unité de soins intensifs. Aucune preuve significative de lésion cardiaque directe n'a été observée dans cette étude. Un score d'échelle de coma à faible Glasgow et un Une fréquence respiratoire accrue à la présentation est associée à de mauvais résultats.

A Programmable Microfluidic Paper-Based Analytical Device for Simultaneous Colorimetric and Photothermal Visual Sensing of Multiple Enzyme Activities.

New strategies for the simultaneous and portable detection of multiple enzyme activities are highly desirable for clinical diagnosis and home care. However, the methods developed thus far generally suffer from high costs, cumbersome procedures, and heavy reliance on large-scale instruments. To satisfy the actual requirements of rapid, accurate, and on-site detection of multiple enzyme activities, we report herein a smartphone-assisted programmable microfluidic paper-based analytical device (µPAD) that utilizes colorimetric and photothermal signals for simultaneous, accurate, and visual quantitative detection of alkaline phosphatase (ALP) and butyrylcholinesterase (BChE). Specifically, the operation of this µPAD sensing platform is based on two sequential steps. Cobalt-doped mesoporous cerium oxide (Co-m-CeO2) with remarkable peroxidase-like activities under neutral conditions first catalytically decomposes H2O2 for effectively converting colorless 3,3',5,5'-tetramethylbenzidine (TMB) into blue oxidized TMB (oxTMB). The subsequent addition of ALP or BChE to their respective substrates produces a reducing substance that can somewhat inhibit the oxTMB transformation for compromised colorimetric and photothermal signals of oxTMB. Notably, these two-step bioenzyme-nanozyme cascade reactions strongly support the straightforward and excellent processability of this platform, which exhibit lower detection limits for ALP and BChE with a detection limit for BChE an order of magnitude lower than those of the other reported paper-based detection methods. The practicability and efficiency of this platform are further demonstrated through the analysis of clinical serum samples. This innovative platform exhibits great potential as a facile yet robust approach for simultaneous, accurate, and on-site visual detection of multiple enzyme activities in authentic samples.

Mass spectrometry detection of organophosphorus pesticide adducts on butyrylcholinesterase and albumin.

This study established a method to prepare and detect OPs adducts on butyrylcholinesterase (BChE) and human serum albumin (HSA). OPs (methyl paraoxon, ethyl paraoxon, methyl parathion, parathion) were incubated with BChE or HSA in vitro, and the adducts of OPs-BChE or OPs-HSA were prepared and qualitatively analyzed by ultra-performance liquid chromatography data-dependent high-resolution tandem mass spectrometry (UPLC-ddHRMS/MS). The amounts of BChE and HSA in the incubating systems were varied and the resulting amounts of the adducts were determined using linear regression. OPs-BChE in the blood were isolated by immunomagnetic separation (IMS), and then digested into the OPs-nonapeptide adduct by pepsin. The proteins in the remaining blood plasma were precipitated and digested by pronase to OPs-tyrosines(OPs-Tyr), which were quantified by UPLC-ddHRMS/MS. 4 OPs-nonapeptides and 4 OPs-Tyr adducts were obtained through the process above. The relative mass deviation of incubated adducts between the actual and theoretical exact masses was less than 10 ppm, and further confirmed by fragmentation mass spectra analysis. Calibration curves were linear for all adducts with a coefficient of determination value (R2) ≥0.995. The limits of detection (LOD) and limits of quantification (LOQ) for adducts detected by MS ranged from 0.05 to 1.0 ng/mL, and from 0.1 to 2.0 ng/mL, respectively. The recovery percentages for adducts ranged from 76.1 % to 107.1 %, matrix effects ranged from 83.4 % to 102.1 %. The inter-day and intra-day precision were 6.1-10.1 % and 6.9-12.9 % for adducts. This study provides a new reference method for the detection of organophosphorus pesticide poisoning. In addition, two blood samples with organophosphorus poisoning were tested by the designed method, and the corresponding adducts were detected in both samples.

Serum Organophosphorus compound levels as a surrogate marker for severity assessment and management in Acute Organophosphorus Poisoning - A novel approach.

Organophosphorus (OP) compounds are the most extensively used pesticides' class worldwide; cause most self­poisoning deaths especially in India. Thus, it is utmost important for early identification and aggressive management of OP poisoning from the clinical perspective to prevent serious complications by using sophisticated LC-MS/MS approach. This was a prospective study involving 103 patients of OP cases admitted to Karnataka Institute of Medical Sciences from June 2022 to May 2023, based on the inclusion and exclusion criteria patients were subjected to study. On admission, venous blood was collected from patient with Malathion and Profenofos OP poisoning history and subjected to serum biomarker and to LC-MS/MS analysis. Out of the 103 patients, 68 patients consumed Profenofos (66%) and 35 patients consumed Malathion (34%). Pseudocholinesterase levels among the of OP cases revealed that the 33 patients had mild toxicity, 40 patients had moderate toxicity and 30 patients had severe toxicity of OP poisoning. Subsequently LC-MS/MS analysis showed that the results obtained are not in correlation with indirect serum marker pseudocholinesterase levels. On the other side, LC-MS/MS results are in correlation with the clinical outcome of the patients with respect to morbidity and mortality. Thus, LC-MS/MS approach to assess the OP levels in patients could be used as potential diagnostic and prognostic marker for the absolute quantification of OP compounds compared to indirect OP levels estimation.

Ratiometric fluorescence and colorimetric strategies for assessing activity of butyrylcholinesterase in human serum using g-C3N4 nanosheets, silver ion and o-phenylenediamine.

Ratiometric fluorescence and colorimetric strategies for detecting activity of butyrylcholinesterase (BChE) in human serum were developed by using g-C3N4 nanosheets, silver ion (Ag+) and o-phenylenediamine (OPD) as chromogenic agents. The oxidation-reduction reaction of OPD and Ag+ generates 2,3-diaminophenazine (oxOPD). Under exciation at 370 nm, g-C3N4 nanosheets and oxOPD emit fluorescence at 440 nm (F440) and 560 nm (F560), respectively. Additionally, oxOPD exhibits quenching ability towards g-C3N4 nanosheets via photoinduced electron transfer (PET) process. Thiocholine (TCh), as a product of BChE-catalyzed hydrolysis reaction of butylthiocholine iodide (BTCh), can coordinate with Ag+ intensively, and consequently diminish the amount of free Ag+ in the testing system. Less amount of free Ag+ leads to less production of oxOPD, resulting in less fluorescence quenching towards g-C3N4 nanosheets as well as less fluorescence emission of oxOPD. Therefore, by using g-C3N4 nanosheets and oxOPD as fluorescence indicators, the intensity ratio of their fluorescence (F440/F560) was calculated and employed to evaluate the activity of BChE. Similarly, the color variation of oxOPD indicated by the absorbance at 420 nm (ΔA420) was monitored for the same purpose. These strategies were validated to be sensitive and selective for detecting BChE activity in human serum, with limits of detection (LODs) of 0.1 U L-1 for ratiometric fluorescence mode and 0.7 U L-1 for colorimetric mode.

Depressive symptoms and suicide attempts among farmers exposed to pesticides.

Pesticides safeguard crop health but may diminish cholinesterase activity in farmers, potentially leading to psychiatric disorders like depression and suicide attempts. This study, with 453 participants (225 pesticide-exposed farmers, 228 non-farmers) in Almería, Spain, aimed to investigate the presence of depressive symptoms and suicide attempts, the decrease acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity, and their relationship with pesticide exposure in farmers. Depressive symptoms were evaluated using the Spanish adaptation of the Beck Depression Inventory, and blood samples were analyzed for AChE and BChE activity. Farmers showed significantly increased risk of moderate/severe depression and suicide attempts compared to non-farmers (OR = 2.18; p = 0.001), with highest risks observed among mancozeb users (OR = 2.76; p = 0.001 for depression) and malathion users (OR = 3.50; p = 0.001 for suicide attempts). Findings emphasize elevated depression and suicide risks among pesticide-exposed farmers, particularly associated with chlorpyrifos, mancozeb, and malathion exposure.

Human Plasma Butyrylcholinesterase Hydrolyzes Atropine: Kinetic and Molecular Modeling Studies.

The participation of butyrylcholinesterase (BChE) in the degradation of atropine has been recurrently addressed for more than 70 years. However, no conclusive answer has been provided for the human enzyme so far. In the present work, a steady-state kinetic analysis performed by spectrophotometry showed that highly purified human plasma BChE tetramer slowly hydrolyzes atropine at pH 7.0 and 25 °C. The affinity of atropine for the enzyme is weak, and the observed kinetic rates versus the atropine concentration was of the first order: the maximum atropine concentration in essays was much less than Km. Thus, the bimolecular rate constant was found to be kcat/Km = 7.7 × 104 M-1 min-1. Rough estimates of catalytic parameters provided slow kcat < 40 min-1 and high Km = 0.3-3.3 mM. Then, using a specific organophosphoryl agent, echothiophate, the time-dependent irreversible inhibition profiles of BChE for hydrolysis of atropine and the standard substrate butyrylthiocholine (BTC) were investigated. This established that both substrates are hydrolyzed at the same site, i.e., S198, as for all substrates of this enzyme. Lastly, molecular docking provided evidence that both atropine isomers bind to the active center of BChE. However, free energy perturbations yielded by the Bennett Acceptance Ratio method suggest that the L-atropine isomer is the most reactive enantiomer. In conclusion, the results provided evidence that plasma BChE slowly hydrolyzes atropine but should have no significant role in its metabolism under current conditions of medical use and even under administration of the highest possible doses of this antimuscarinic drug.

Baseline physiological data from anesthetized pigs in a VX intoxication model.

Over the past fifty years, swine models have been used for organophosphorus intoxication studies. Among these studies and others on the swine model in general, some physiological data, especially cholinesterase activity highly impacted by organophosphorus compounds like nerve agent VX, still need to be completed. To support and compare our model to others, we have published the experimental protocol, the physiological values of 31 juvenile anesthetized pigs, and the 6 h-follow-up of six supplementary anesthetized control animals and 7 VX-intoxicated pigs. We reported hemodynamics and respiratory parameters, blood levels in several biochemical parameters, blood gas, and complete blood count and compared them to the literature. We also focused on tissue and blood cholinesterase activities and detailed them for acetylcholinesterase and butyrylcholinesterase. After establishing a broad physiological data set consistent with the literature, we reported several cardio-respiratory parameters that seem more affected by an organophosphate intoxication, like heart rate, arterial blood pressure, cardiac output, and respiratory rate. Within the blood, oxygen saturation (SpO2), lactatemia, base excess, and glycemia can also be measured and associated with the other parameters to evaluate the life-threatening status. This swine model is currently used to develop and evaluate medical countermeasures against organophosphate nerve agent intoxications.

Pseudocholinesterase as a Biomarker for Untreated Wilson's Disease.

The aim of this study was to demonstrate that pseudocholinesterase (CHE) serum level is a useful diagnostic biomarker for untreated Wilson's disease (WD). Between 2013 and 2019, about 75 patients were referred to the outpatient department of the University of Düsseldorf with suspected Wilson's disease. In 31 patients with suspected Wilson's disease (WD-SUS-group), WD was excluded by means of investigations other than analysis of blood and urine. A total of 27 parameters of blood and urine in these 31 patients were compared to those of 20 de novo patients with manifest WD (WD-DEF-group), which parameter showed the highest significance level of difference between the WD-DEF-group and the WD-SUS-group. Thereafter, receiver operating characteristics (ROC-curves) were analyzed to evaluate which parameter showed the largest area under the curve (AUC) to detect WD. Finally, a logistic regression analysis was performed to analyze which combination of parameters allowed the best classification of the 51 patients either into the WD-DEF-group or into the WD-SUS-group. CHE showed the highest significance level for a difference between the WD-DEF- and WD-SUS-group, had the highest AUC, and, in combination with ceruloplasmin, allowed 100% correct classification. Without CHE, no other combination of parameters reached this level of correct classification. After the initiation of treatment, which regularly results in an improvement in CHE, the high diagnostic accuracy of this biomarker was lost. Cholinesterase turns out to be an excellent biomarker for differentiation between untreated de novo patients with manifest WD and heterozygotic gene carriers.

Pesticide toxicity assessment and geographic information system (GIS) application in small-scale rice farming operations, Thailand.

The objectives of the study were to evaluate the impact of pesticide exposure on farmer health during non-active rice farming and active rice farming periods and present the change in the individual cholinesterase activities (%reduction) on the geographic information system (GIS) mapping in Nakhon Ratchasima Province, Thailand. Acetyl- and butyryl-cholinesterase (AChE and BuChE) activities were monitored during both study periods using Test-mate ChE (Model 400). The location of paddy fields was specified using Garmin geographic positioning system MAP 62s. Fifty-eight farmers who participated in this study had an average age of 49.2 ± 6.9 years. Higher prevalence of all health symptoms was observed among farmer participants during the active rice farming period comparing to the non-active rice farming period (p < 0.01). Furthermore, farmers had significantly lower activities of AChE and BuChE during the active rice farming period comparing to the non-active rice farming period (p < 0.01). Our findings indicate that the GIS mapping indicate that the cases with a significant enzyme inhibition have dispersed across the agricultural and the nearby residential areas. This, investigation can be used to promote safer use of pesticides among farmers and mitigate pesticide exposure among residents living in close proximity to a rice field.

Point-of-care testing of butyrylcholinesterase activity through modulating the photothermal effect of cuprous oxide nanoparticles.

Butyrylcholinesterase (BChE) is an important indicator for clinical diagnosis of liver dysfunction, organophosphate toxicity, and poststroke dementia. Point-of-care testing (POCT) of BChE activity is still a challenge, which is a critical requirement for the modern clinical diagnose. A portable photothermal BChE assay is proposed through modulating the photothermal effects of Cu2O nanoparticles. BChE can catalyze the decomposition of butyrylcholine, producing thiocholine, which further reduce and coordinate with CuO on surface of Cu2O nanoparticle. This leads to higher efficiency of formation of Cu9S8 nanoparticles, through the reaction between Cu2O nanoparticle and NaHS, together with the promotion of photothermal conversion efficiency from 3.1 to 59.0%, under the excitation of 1064 nm laser radiation. An excellent linear relationship between the temperature change and the logarithm of BChE concentration is obtained in the range 1.0 to 7.5 U/mL, with a limit of detection of 0.076 U/mL. In addition, the portable photothermal assay shows strong detection robustness, which endows the accurate detection of BChE in human serum, together with the screening and quantification of organophosphorus pesticides. Such a simple, sensitive, and robust assay shows great potential for the applications to clinical BChE detection and brings a new horizon for the development of temperature based POCT.

Cholinesterase activity in serum during general anesthesia in patients with or without vascular disease.

Maintaining hemodynamic stability during the induction and maintenance of anesthesia is one of the challenges of the anesthesiologist. Patients with vascular disease are at increased risk of instability due to imbalance between the sympathetic and parasympathetic parts of the autonomic nervous system, a balance accessible by serum cholinesterase activity. We aim to characterize the dynamics of cholinesterase activity in patients undergoing general anesthesia (GA) and surgery. This was a prospective study of 57 patients undergoing ambulatory or vascular surgery under GA. Cholinesterase activity was measured before the induction of anesthesia, after 15 min and at the end of surgery by calculating the capacity of serum acetylcholinesterase (AChE) and butyrylcholinesterase to hydrolyze AcetylThioCholine. Data on atherosclerotic disease, anesthesia management were analyzed. Both AChE and total cholinergic status (CS) decreased significantly after GA induction at 15 min and even more so by the end of surgery. Vascular surgery patients had lower baseline cholinesterase activity compared to ambulatory surgery patients. Patients requiring intraoperative administration of phenylephrine for hemodynamic support (21.1%) had a significantly lower level of AChE and CS compared to untreated patients. Our findings serve as a mirror to the sympathetic/parasympathetic imbalance during GA, with a marked decrease in the parasympathetic tone. The data of a subgroup analysis show a correlation between low cholinesterase activity and an increase in the need for hemodynamic support.

Identification and Study of Biomarkers from Novichok-Inhibited Butyrylcholinesterase in Human Plasma.

To identify biomarkers of ethyl (1-(diethylamino)ethylidene)phosphoramidofluoridate (A234)- or methyl (1-(diethylamino)ethylidene)phosphoramidofluoridate (A232)-inhibited butyrylcholinesterase (BChE), we investigated nonapeptide adducts containing the active site serine, which plays a key role in enzyme activity, using LC-MS/HRMS. Biomarkers were acquired as expected, and they exhibited a significant amount of fragment ions from the inhibiting agent itself, in contrast to the MS2 spectra of conventional nerve agents. These biomarkers had a higher abundance of [M+2H]2+ ions than [M+H]+ ions, making doubly charged ions more suitable for trace analysis.

Reactivation of organophosphate-inhibited serum butyrylcholinesterase by novel substituted phenoxyalkyl pyridinium oximes and traditional oximes.

Organophosphorus compounds (OPs) include nerve agents and insecticides that potently inhibit acetylcholinesterase (AChE), an essential enzyme found throughout the nervous system. High exposure levels to OPs lead to seizures, cardiac arrest, and death if left untreated. Oximes are a critical piece to the therapeutic regimen which remove the OP from the inhibited AChE and restore normal cholinergic function. The current oximes 2-PAM, MMB-4, TMB-4, HI-6, and obidoxime (OBD) have two drawbacks: lack of broad spectrum protection against multiple OP structures and poor brain penetration to protect against OP central neurotoxicity. An alternative strategy to enhance therapy is reactivation of serum butyrylcholinesterase (BChE). BChE is stoichiometrically inhibited by OPs with no apparent toxic result. Inhibition of BChE in the serum followed by reactivation could create a pseudo-catalytic scavenger allowing numerous regenerations of BChE to detoxify circulating OP molecules before they can reach target AChE. BChE in serum from rats, guinea pigs or humans was screened for the reactivation potential of our novel substituted phenoxyalkyl pyridinium oximes, plus 2-PAM, MMB-4, TMB-4, HI-6, and OBD (100µM) in vitro after inhibition by highly relevant surrogates of sarin, VX, and cyclosarin, and also DFP, and the insecticidal active metabolites paraoxon, phorate-oxon, and phorate-oxon sulfoxide. Novel oxime 15 demonstrated significant broad spectrum reactivation of OP-inhibited rat serum BChE while novel oxime 20 demonstrated significant broad spectrum reactivation of OP-inhibited human serum BChE. All tested oximes were poor reactivators of OP-inhibited guinea pig serum BChE. The bis-pyridinium oximes were poor BChE reactivators overall. BChE reactivation may be an additional mechanism to attenuate OP toxicity and contribute to therapeutic efficacy.

Effect of pesticide exposure on total antioxidant capacity and biochemical parameters in Brazilian soybean farmers.

Farmers represent a population highly vulnerable to the toxic effects of pesticide exposure. Antioxidant capacity and biochemical parameters have been used as biomarkers of occupational exposure to pesticides. The aim of this study was to evaluate hepatic and renal parameters as well as butyrylcholinesterase (BChE) activity and ferric-reducing ability of plasma (FRAP) considering high and low exposure periods in soybean farmers in southern Brazil. The exposed group consisted of 50 soybean farmers. Two control groups were used, composed by 35 (Novo Hamburgo control group) and 28 (Sertão control group) subjects not exposed to pesticides. Farmers blood samples were collected during the high and low pesticide exposure periods. BChE, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), urea, and creatinine levels were determined. The FRAP assay was carried out to evaluate the antioxidant potential in the exposed group. Considering the exposed group, significantly lower BChE and increased AST activity were observed during high pesticide exposure period as well as higher FRAP, urea and creatinine levels; however, ALT and GGT did not differ between the two periods. When compared with the control groups, only urea and creatinine were higher in the exposed group. The present results indicate that occupational exposure to mixtures of pesticides might elicit adverse effects at the biochemical level. In addition, the study highlights the importance in considering periods of a same crop season with different degree of pesticide exposure during biologic monitoring of these biochemical parameters.

Chemical composition, in vitro antioxidant, anticholinesterase and antibacterial activities of Linaria scariosa Desf.

The study was performed on the dichloromethane (DCM), ethyl acetate (EAc) and n-butanol (Bu) fractions (F) obtained from the 80% ethanol extract of Linaria scariosa Desf. aerial parts, collected in the North Eastern region of Algeria. Remarkable total phenolic and flavonoid contents were obtained, mainly for EAcF. These results were in accordance with the antioxidant activity of EAcF against DPPH, ABTS, CUPRAC and reducing power tests. DCMF and BuF exhibited significant cholinesterase activity inhibition of BChE and AChE. Moreover, EAcF displayed only moderate antibacterial activities, especially against S. aureus. The biological results were correlated to the chemical components, deduced by both GC-MS analysis of the fractions and the isolation of hemipholin, pectolinarigenin, antirride, antirrinoside, pectolinarin and linariosise, some of which known to exhibit potent effects on the tested biological activities. The study provides the first biological and chemical investigation on Linaria scariosa Desf (unresolved name).

Nondestructive biomarkers in giant toad (Rhinella marina) to assess the effect of complex mixture of pollutants in Coatzacoalcos River, Mexico.

In this study, we evaluated the usefulness of nondestructive biomarkers approach in giant toads (Rhinella marina). We obtained blood samples and the residual condition index of toads from rural and industrial zones from Coatzacoalcos River, Mexico (COA). In the blood samples, we determined the activity of enzymes, lipid peroxidation, and the presence of cell death (apoptosis). We found that the activity of the enzyme delta-aminolevulinic dehydratase was lower. Still, the glutathione s-transferase activity and the percentage of apoptosis in erythrocytes were higher in the toads of COA than laboratory toads. Meanwhile, some biomarkers in toads showed differences when compared between Industrial and Rural zones. These results and correlations between biomarkers showed how the response changed in the toads living near the industrial zones. We demonstrate that a nondestructive biomarkers approach can be useful in environmental studies with anuran amphibians.

Effects of low-level imidacloprid oral exposure on cholinesterase activity, oxidative stress responses, and primary DNA damage in the blood and brain of male Wistar rats.

Imidacloprid is a neonicotinoid insecticide that acts selectively as an agonist on insect nicotinic acetylcholine receptors. It is used for crop protection worldwide, as well as for non-agricultural uses. Imidacloprid systemic accumulation in food is an important source of imidacloprid exposure. Due to the undisputable need for investigations of imidacloprid toxicity in non-target species, we evaluated the effects of a 28-day oral exposure to low doses of imidacloprid (0.06 mg/kg b. w./day, 0.8 mg/kg b. w./day and 2.25 mg/kg b. w./day) on cholinesterase activity, oxidative stress responses and primary DNA damage in the blood and brain tissue of male Wistar rats. Exposure to imidacloprid did not cause significant changes in total cholinesterase, acetylcholinesterase and butyrylcholinesterase activities in plasma and brain tissue. Reactive oxygen species levels and lipid peroxidation increased significantly in the plasma of rats treated with the lowest dose of imidacloprid. Activities of glutathione-peroxidase in plasma and brain and superoxide dismutase in erythrocytes increased significantly at the highest applied dose. High performance liquid chromatography with UV diode array detector revealed the presence of imidacloprid in the plasma of all the treated animals and in the brain of the animals treated with the two higher doses. The alkaline comet assay results showed significant peripheral blood leukocyte damage at the lowest dose of imidacloprid and dose-dependent brain cell DNA damage. Oral 28-day exposure to low doses of imidacloprid in rats resulted in detectable levels of imidacloprid in plasma and brain tissue that directly induced DNA damage, particularly in brain tissue, with slight changes in plasma oxidative stress parameters.

Butyrylcholinesterase: An economical marker of disease activity in oral squamous cell carcinoma before and after therapy.

INTRODUCTION: Biomarkers which can predict disease progression and serve as prognostic indicators are necessary for better management of oral cancer. Studies have shown that Cholinesterase plays an important role in cellular proliferation, differentiation and may have a possible involvement in tumor growth. AIM AND OBJECTIVE: The present study is aimed to determine the utility of serum Butyrylcholinesterase (BChe) levels as a marker for progression of oral squamous cell carcinoma (OSCC) in relation to the grade of the tumor and to determine if any variation occurred in the levels of BChe before and after therapy. MATERIALS AND METHODS: A total of 120 patients were included in the study and divided into two groups as Group A-30 patients (healthy individuals) and Group B-90 cases of histopathologically diagnosed OSCC. The blood sample was collected before surgery, re-collected after the completion of radiotherapy (i.e., 3 and 6 months postsurgery) and analyzed biochemically for the concentration of BCh. STATISTICAL ANALYSIS: Paired t-test, ANOVA, and post hoc test (Bonferroni) were used for determining the statistical significance. RESULTS: BChe levels were lower in OSCC (2940.32-1405.50 u/l when compared with controls (11149.60-11243.07 unit/l) and this difference was statistically significant. Postoperatively at 3 months, the serum BChe levels of OSCC patients increased almost two-fold compared to the preoperative values, and this difference was also statistically significant (P = 0.000) After 6 months, these levels further increased but did not reach those of controls. CONCLUSION: BChe can be used as an inexpensive, easy to use, noninvasive biomarker for the evaluation of disease-free survival in OSCC patients.

In Situ Generation of Prussian Blue by MIL-53 (Fe) for Point-of-Care Testing of Butyrylcholinesterase Activity Using a Portable High-Throughput Photothermal Device.

Butyrylcholinesterase (BuChE), the primary source of serum cholinesterase activity, is an indispensable biochemical marker for clinical diagnosis of liver function and organophosphorus poisoning. The requirement for bulky and expensive instruments represents a huge hindrance for point-of-care testing (POCT) of BuChE, especially in resource-limited settings. Herein, an easy-operated, economic, and portable photothermal (PT) biosensing platform for high-throughput BuChE detection was rationally designed. BuChE could "light up" the PT signal through in situ generation of Prussian blue (PB) by MIL-53 (Fe), which allowed us to translate biological signals into temperature signals. Such temperature change signals could be monitored at high throughput (six samples for a single measurement) by a miniature self-made integrated PT device via combining separable 96-well plates, a three-dimensional (3D) printed sample bracket, 808 nm lasers, and thermometers, satisfying the requirement for rapid on-site detection in a large batch with low cost. In addition, the large specific surface area, 3D network structure, and high porosity of MIL-53 (Fe) offered a beneficial platform for its reaction with enzymatic hydrolysate, resulting in high sensing sensitivity and low detection limit (0.3 U L-1), which was at least 20 000 times lower than the normal human serum BuChE activity. This facile, affordable, and broad applicability PT sensing platform provides a beneficial reference for the rational design of other disease diagnostic approaches suitable for POCT.