8-Hydroxyquinolylnitrones as multifunctional ligands for the therapy of neurodegenerative diseases

We describe the development of quinolylnitrones (QNs) as multifunctional ligands inhibiting cholinesterases (ChEs: acetylcholinesterase and butyrylcholinesterase-hBChE) and monoamine oxidases (hMAO-A/B) for the therapy of neurodegenerative diseases. We identified QN 19, a simple, low molecular weight nitrone, that is readily synthesized from commercially available 8-hydroxyquinoline-2-carbaldehyde. Quinolylnitrone 19 has no typical pharmacophoric element to suggest ChE or MAO inhibition, yet unexpectedly showed potent inhibition of hBChE (IC50 = 1.06 ± 0.31 nmol/L) and hMAO-B (IC50 = 4.46 ± 0.18 μmol/L). The crystal structures of 19 with hBChE and hMAO-B provided the structural basis for potent binding, which was further studied by enzyme kinetics. Compound 19 acted as a free radical scavenger and biometal chelator, crossed the blood-brain barrier, was not cytotoxic, and showed neuroprotective properties in a 6-hydroxydopamine cell model of Parkinson's disease. In addition, in vivo studies showed the anti-amnesic effect of 19 in the scopolamine-induced mouse model of AD without adverse effects on motoric function and coordination. Importantly, chronic treatment of double transgenic APPswe-PS1δE9 mice with 19 reduced amyloid plaque load in the hippocampus and cortex of female mice, underscoring the disease-modifying effect of QN 19.

Protective effect of huperzine A on phenytoin induced cognition impairment: Behavioral and biochemical study

Phenytoin, a drug of choice for Epilepsy is also known for its adverse effects. The most common adverse effect due to phenytoin is cognition impairment. Cognition impairment is a serious problem in society as it debars the person's social life. Thus to overcome such a problem demand for a solution arises. Huperzine, sesquiterpene alkaloids having immense neuroprotective properties. Thus in this study, it was aimed to evaluate the effectiveness of huperzine on Phenytoin- induced Cognition Impairment. The protective effect of huperzine on phenytoin-induced cognition impairment was evaluated in rats. The effect of Huperzine on phenytoin-induced cognitive impairment was evaluated by behavioral, biochemical, and histopathological studies. The co-administration of huperzine with phenytoin showed significant results. The treatment of Huperzine with phenytoin resulted in significant improvement in learning and memory. The oxidative stress induced by Phenytoin was reversed by huperzine. A significant decrease in cholinesterase activity was also observed. The histopathology showed damaged neuronal cells in periventricular regions and cortex due to phenytoin which was altered by Huperzine. Thus, the present study demonstrates the protective effect of huperzine on phenytoin-induced cognition impairment.

Anticholinesterase activity of ß-carboline-1, 3, 5-triazine hybrids

Abstract The ß-carboline-1,3,5-triazine hydrochlorides 8-13 were evaluated in vitro against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The analysed compounds were selective to BuChE, with IC50 values in the range from 1.0-18.8 µM being obtained. The N-{2-[(4,6-dihydrazinyl-1,3,5-triazin-2-yl)amino]ethyl}-1-phenyl-ß-carboline-3-carboxamide (12) was the most potent compound and kinetic studies indicate that it acts as a competitive inhibitor of BuChE. Molecular docking studies show that 12 strongly interacts with the residues of His438 (residue of the catalytic triad) and Trp82 (residue of catalytic anionic site), confirming that this compound competes with the same binding site of the butyrylthiocholine

Deficiencia de butirilcolinesterasa: Una revisión narrativa de la literatura / Butirilcholinesterase Deficiency: A Narrative Review of Literature

RESUMEN La butirilcolinesterasa es una enzima que metaboliza relajantes neuromusculares despolarizantes como la succinilcolina, fármaco de elección para procedimientos que requieran parálisis muscular a corto plazo como facilitar la intubación endotraqueal en pacientes sometidos a procedimientos de emergencia. La deficiencia de butirilcolinesterasa se define como la reducción cuantitativa de dicha enzima y su actividad para hidrolizar moléculas, constituyéndose en la principal causa de bloqueo neuromuscular prolongado tras la administración de relajantes neuromusculares como la succinilcolina. Es una condición patológica que puede ser de origen hereditario o adquirido; siendo más común la deficiencia enzimática de origen genético y de carácter autosómico recesivo, la cual se presenta aproximadamente en una de cada 3200 a 5000 personas en todo el mundo. Su manifestación clínica se caracteriza por relajación muscular persistente, la cual puede producir insuficiencia respiratoria aguda. El diagnóstico debe estar orientado a la identificación de sus características clínicas, la cuantificación serológica y el monitoreo neuromuscular. Debido a que no existe cura para esta deficiencia, el manejo debe estar orientado a realizar ventilación mecánica del paciente hasta que el medicamento empleado se metabolice por completo. Este artículo tiene como objetivo realizar una revisión del estado del arte, describiendo su epidemiología, etiología, fisiopatología, manifestaciones clínicas y actualidades en su diagnóstico y tratamiento.

ABSTRACT Butyrylcholinesterase is an enzyme that metabolizes depolarizing neuromuscular relaxants, such as succinylcholine, a chosen medication for procedures that require short-term muscular paralysis, to facilitate endotracheal intubation in patients undergoing emergency procedures, for example. Butyrylcholinesterase deficiency can be defined as a quantitative reduction of the enzyme and its activity to hydrolyze molecules, becoming the main cause of prolonged neuromuscular blockade after the administration of neuromuscular relaxants such as succinylcholine. It is a pathological condition that can be of either hereditary or acquired origin; being more common the enzymatic deficiency of genetic origin and of auto-somal recessive character, occurring in approximately one in 3,200 to 5,000 people worldwide. Its clinical manifestation is characterized by persistent muscle relaxation which can lead to acute respiratory failure. The diagnosis must be oriented to the identification of its clinical characteristics, serological quantification, and neuromuscular monitoring. Because a cure does not exist for this deficiency, management should be directed to mechanical ventilation of the patient, until the used drug is fully metabolized. This article aims to review the state of the art, describing its epidemiology, etiology, pathophysiology, clinical manifestations, and updates in its diagnosis and treatment.

Valores normais da atividade da colinesterase plasmática em anseriformes, com destaque para Alopochen aegyptiacus / Normal values of plasma cholinesterase activity in anseriformes, with emphasis on Alopochen aegyptiacus

A inibição da enzima colinesterase plasmática (BChE) pode ser utilizada como biomarcador para os efeitos da intoxicação por organofosforados e carbamatos. Nas aves, esta inibição ocorre de forma mais acentuada que nos mamíferos, porém poucos são os trabalhos publicados nestas espécies. O objetivo do estudo fo a dosagem da BChE em gansos-egípcios (Alopochen aegyptiacus) e nos anseriformes domésticos: gansos-domésticos (Anser anser domesticus) e marrecos (Anas platyrhynchos domesticus), para o estabelecimento de valores de referência normais. O trabalho possui ineditismo com relação à determinação desta enzima nos gansos-egípcios e domésticos. Os gansos e marrecos são mantidos em confinamento com fornecimento de alimentos e água ad libitum e em espaço adequado à sua manutenção no Instituto Adolfo Lutz (IAL), com a finalidade de fornecimento de sangue para a alimentação de triatomídeos do insetário de criação no Núcleo de Parasitoses Sistêmicas. Nos Alopochen aegyptiacus a média e o desvio padrão da BChE foram de 1.868 + 263,6 U/L, nos Anser anser domesticus 2.311 + 673,2 U/L e nos Anas platyrhynchos domesticus 4.290 + 86,11 U/L. (AU)

The inhibition of the plasma cholinesterase enzyme (BChE) can be used as a biomarker for the effects of intoxication by organophosphates and carbamates. In birds, this inhibition is more pronounced than in mammals, however there are few specific studies were conducted in this field. The aim of this study was to measure BChE in Egyptian geese (Alopochen aegyptiacus) and domestic anseriforms: domestic geese (Anser anser domesticus) and mallards (Anas platyrhynchos domesticus), not exposed to pesticides, for the establishment of normal values. The work is unprecedented regarding the determination of this enzyme in egyptian geese and domestic geese. Geese and mallards are kept in confinement with ad liditum food and water supply and in adequate space for their maintenance at the Adolfo Lutz Institute (IAL), for the purpose of supplying blood for the feeding of triatomines from the insectary of the Nucleus of Systemic Parasitoses. In Alopochen aegyptiacus the mean and standard deviation of BChE were 1,868 + 263,6 U/L, in Anser anser domesticus 2,311 + 673,2 U/L and in Anas platyrhynchos domesticus 4,290 + 86.11 U/L. (AU)

Ocotea daphnifolia: phytochemical investigation, in vitro dual cholinesterase inhibition, and molecular docking studies

This study aimed to evaluate the anticholinesterase activities of extracts and fractions of Ocotea daphnifolia in vitro and characterize its constituents. The effects of hexane, ethyl acetate, and ethanolic extracts on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activity were determined with a spectrophotometry assay. All extracts inhibited cholinesterase activity, and the ethanolic extract (2 mg/mL) exhibited the highest inhibition of both enzymes (99.7% for BuChE and 82.4% for AChE). The ethanolic extract was fractionated by column chromatography resulting in 14 fractions that were also screened for their anticholinesterase effects. Fraction 9 (2 mg/mL) showed the highest activity, inhibiting AChE and BuChE by 71.8% and 90.2%, respectively. This fraction was analyzed by high-performance liquid chromatography high-resolution mass spectrometry which allowed the characterization of seven glycosylated flavonoids (containing kaempferol and quercetin nucleus) and one alkaloid (reticuline). In order to better understand the enzyme-inhibitor interaction of the reticuline toward cholinesterase, molecular modeling studies were performed. Reticuline targeted the catalytic activity site of the enzymes. Ocotea daphnifolia exhibits a dual cholinesterase inhibitory activity and displays the same pattern of intermolecular interactions as described in the literature. The alkaloid reticuline can be considered as an important bioactive constituent of this plant.

Influence of galantamine in the inflammatory process and tissular lesions caused by Trypanosoma cruzi QM2 strain

Abstract INTRODUCTION: Trypanosoma cruzi infection triggers an inflammatory process with exacerbated production of cytokines that stimulate inflammatory and anti-inflammatory signals, including the efferent anti-inflammatory signal known as the anti-inflammatory cholinergic pathway. Thus, the use of anticholinesterase drugs, such as galantamine, could minimize the inflammatory process caused by this disease. METHODS For the study at 30, 60, and 90 days, 120 Swiss mice were divided into three groups. Each group was subdivided into four subgroups: uninfected/untreated (CTRL), uninfected/treated (GAL), infected/untreated (INF), and infected/treated (GAL/INF). The infected groups were inoculated intraperitoneally with 0.1 ml of mouse blood containing 5 × 104 trypomastigote forms of the T. cruzi QM2 strain. The galantamine-treated groups received 5 mg/kg of galantamine orally, through pipetting. From each subgroup, the parameters of parasitemia, histopathological analysis, butyrylcholinesterase activity (BuChE), and functional study of the colon were evaluated. RESULTS: BuChE performance was observed when AChE was suppressed, with increased activity in the GAL/INF group similar to the INF group on the 30th day post infection, thus corroborating the absence of a significant difference in parasitic curves and histopathological analysis. CONCLUSIONS: The presence of an inflammatory process and nests of amastigotes, as well as evidence of reactivity to ACh and NOR, suggest that galantamine did not interfere with the colonic inflammatory response or even in colonic tissue parasitism at this stage of Chagas disease.

Donepezil: A review of the recent structural modifications and their impact on anti-Alzheimer activity

Alzheimer disease (AD) is characterized by a low level of acetylcholine, beta-amyloid (Aβ) aggregation and oxidative stress. Donepezil is the core medicine used for the treatment of AD. Various structural modifications of donepezil have been carried out. Benzylpiperidine part of donepezil has been replaced with benzylpyridine, pyridyl methylpiperidine, benzylpiperazine, pyrimidyl piperazine. These derived molecules showed promising activities as anti-Alzheimer agents. Replacement of indanone part by other heterocyclic rings such as pyridine resulted in the formation of compounds which exhibited monoamine oxidase (MAO) as well as acetylcholinesterase (AChE) inhibition. Propargylamine containing derivatives displayed AChE as well as MAO inhibition properties. Attachment of donepezil with natural compounds like ferulic acid, flavonoids, and curcumin showed antioxidant activities in addition to inhibition of the AChE. Benzylpiperidine and benzylpiperazine have also been combined with condensed heterocyclic rings and these compounds displayed promising anti-Alzheimer properties. This review highlights the important structural modifications of donepezil and their influence on biological activities as anti-Alzheimer agents.

In vitro screening for acetylcholinesterase and butyrylcholinesterase inhibition and antimicrobial activity of chia seeds (Salvia hispanica)

BACKGROUND: Chia seeds are gaining increasing interest among food producers and consumers because of their prohealth properties. RESULTS: The aim of this work was to evaluate the potential of chia seeds to act as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors. The highest inhibitory activity against AChE and BChE was observed for colored seed ethanol extracts. A positive correlation was found between the presence of quercetin and isoquercetin as well as protocatechuic, hydroxybenzoic, and coumaric acids and the activity of extracts as AChE and BChE inhibitors. It has also been shown that grain fragmentation affects the increase in the activity of seeds against cholinesterases (ChE). Furthermore, seeds have been shown to be a source of substances that inhibit microbial growth. CONCLUSIONS: It was found that the chia seed extracts are rich in polyphenols and inhibit the activity of ChEs; therefore, their use can be considered in further research in the field of treatment and prevention of neurodegenerative diseases.

In vitro Antioxidant and Cholinesterase Inhibitory Activities of Methanolic Extract of Grewia nervosa L. (Family: Tiliaceae) Leaf

Aims: The methanolic extract of Grewia nervosa L. leaves belongs to the family of Tiliaceae. The purpose of this study was to evaluate total phenolics, total flavonoids, total proanthocyanidins, total antioxidant capacity, iron reducing power capacity, free radical scavenging activity, hydroxyl radical scavenging activity, Lipid peroxidation inhibition activity, anti-acetylcholinestrase activity, anti-butyrylcholinestrase activity, metal chelating activity, total flavonols, nitric oxide radical scavenging activity and phytochemical screening. Place and Duration of Study: The study was carried out between April 2015 to June 2015 in the Department of Pharmacy, Southeast University, Dhaka, Bangladesh. Methodology: Antioxidant activity and neuroprotective activities were determined by several standard methods. Phytochemical screening was done by characteristic colour changes or colour precipitate using standard phytochemical reaction methods. Results: The anti-acetylcholinesterase activity of different extracts of G. nervosa was assessed by a slightly modified Ellman coupled enzyme assay. IC50 of the crude extract and its fractions petroleum ether fraction (PEF), chloroform fraction (CLF), ethyl acetate fraction (EAF) and aqueous fraction (AQF) was found to be 17.07 µg/ml, 15.08 µg/ml, 135.57 µg/ml, 274.78 µg/ml respectively. In butyrylcholinesterase inhibitory assay, the lowest activity was found in PTEF with IC50 value 15.79 and the highest activity was found in CLF with IC50 value 7.55. The crude methanol extract and its different fractions showed considerable total antioxidant activity and reducing capacity. In DPPH scavenging assay and hydroxyl radical scavenging assay, the crude methanol extract showed 79.54% and 89.54% scavenging having IC50 of 11.36 and 15.06 μg/ml respectively. Among the fractions, ethyl acetate exhibited the highest DPPH scavenging activity with IC50 of 14.98 μg/ml, while the petroleum ether fraction exhibited the lowest activity with IC50 of 553.09 μg/ml. In hydroxyl radical scavenging activity aqueous fraction exhibited the highest scavenging activity with IC50 of 14.84 μg/ml, while petroleum ether fraction exhibited the lowest activity with IC50 of 33.39 μg/ml. In the lipid peroxidation assay, crude methanol extract showed significant inhibition of peroxidation at all concentrations, with IC50 of 54.41 μg/ml. Among the fractions, ethyl acetate fraction demonstrated the highest activity with IC50 of 33.46 μg/ml. Conclusion: Observing the in-vitro studies, it can be concluded that the methanolic extract of G. nervosa leaves could be used in different diseases because of its effective pharmacological properties. So, further studies are recommended to isolate the exact compounds responsible for this activity and their efficacy needs to be tested.

Evaluation of Antioxidant and Cholinesterase Inhibitory Activities of Hoya parasitica Variegata - An In-vitro Study

Aim: Oxidative stress is responsible for the development of different neurological disorders such as Alzheimer’s disease (AD). In the present study, Hoya parasitica variegata belonging to the family Apocynaceae was evaluated for its cholinesterase inhibitory and antioxidant activities with an objective of searching a new natural source to treat different neurological disorders. Study Design: The methanolic extract of H. parasitica was subjected for in-vitro evaluation which included antioxidant and cholinesterase inhibitory activities. Place and Duration of Study: Department of Pharmacy, Southeast University, Banani, Dhaka-1213, Bangladesh, from July to December 2016. Methodology: The cholinesterase inhibitory and antioxidant activities were assessed by total phenol content, flavonoid content, total antioxidant, iron reducing power capacity, DPPH and hydroxyl radical scavenging capacity, lipid peroxidation inhibition, metal chelating activity as well as acetylcholinestrase (AChE) and butyrylcholinestrase (BChE) inhibitory activities. Results: Total phenolic and flavonoid content of the extract were 53.31 mg of gallic acid and 129.88 mg of quercetin equivalent respectively. The methanolic extract of H. parasitica (MEHP) showed considerable total antioxidant activity and reducing capacity. In DPPH and hydroxyl radical scavenging assay, the MEHP showed IC50 of 485 μg/mL and 39.65 μg/mL respectively. In lipid peroxidation inhibition activity MEHP showed IC50 value of 857.63 μg/mL and exhibited metal chelating activity with IC50 value 961.21 μg/mL. The MEHP represented inhibition of bovine brain acetylcholinesterase and human blood butyrylcholinesterase and the IC50 value was 269.5 μg/mL and 343.14 μg/mL respectively. Conclusion: The results obtained from present study revealed that MEHP has considerable amount of antioxidant activity as well as anti-acetylcholinesterase and anti-butyrylcholinesterase activity suggesting its potential use in different neurological disorders such as AD.

Deficiencia de butirilcolinesterasa identificada después de la administración de succinilcolina. Reporte del caso / Butyrylcholinesterase deficiency identified after succinylcholine administration. Case report

RESUMEN La función principal de la enzima butirilcolinesterasa es hidrolizar ésteres exógenos como los que están presentes en el relajante neuromuscular succinilcolina, que se utiliza con frecuencia en procedimientos quirúrgicos de corta duración. Se considera que la herencia de butirilcolinesterasa atípica o deficiencia de butirilcolinesterasa es un rasgo autosómico recesivo que se presenta aproximadamente en una de cada 3200 a 5000 personas. Dicha deficiencia puede tener consecuencias graves en pacientes anestesiados con dicho relajante porque en ocasiones causa prolongación de la parálisis o apnea posoperatoria. Se presenta el caso de una paciente de 73 años admitida al servicio de cirugía para una tiroidectomía subtotal. Finalizada la intervención, no emergió espontáneamente del anestésico, presentó signos de relajación con mal esfuerzo inspiratorio y sin recuperar la respuesta neuromuscular; por ello se procedió a revertir con neostigmina, previa aplicación de atropina. La reversión falló por lo que fue trasladada a la unidad de cuidados intensivos. En los exámenes se halló reducido el nivel de colinesterasa sérica, lo que indicó una deficiencia de butirilcolinesterasa compatible con sus síntomas. Tal situación está descrita en la literatura médica.

SUMMARY The main function of the enzyme butyrylcholinesterase is to hydrolyze exogenous esters such as those present in the neuromuscular blocking agent succinylcholine, which is frequently used in short surgical procedures. Inheritance of atypical butyrylcholinesterase or butyrylcholinesterase deficiency is considered an autosomal recessive characteristic and occurs worldwide in approximately one out of 3200 to 5000 people. Such deficiency may have serious consequences for patients anesthetized with that relaxant because sometimes it causes an extension of paralysis or postoperative apnea. We report the case of a 73-year-old woman submitted to subtotal thyroidectomy. After surgery, she did not spontaneously emerge from anesthesia, had signs of relaxation with poor inspiratory effort, and no recovery of neuromuscular response. After application of atropine, reversal was attempted with neostigmine, but it failed, and she was transferred to the ICU. Laboratory results revealed a reduced level of serum cholinesterase indicating a deficiency in butyrylcholinesterase consistent with her symptoms. Such situation has been described in medical literature.

Phytochemical composition of Caesalpinia crista extract as potential source for inhibiting cholinesterase and β-amyloid aggregation: Significance to Alzheimer's disease

Objective: To screen plant extract fractions and elucidate the components present in Caesalpinia crista (C. crista) leaves for cholinergic and anti-amyloidogenic activities for the treatment of Alzheimer's diseases. Methods: This work has been carried out to study the action of C. crista extracts from nonpolar to polar solvents toward inhibition of oxidative stress, cholinergic and amyloidosis. The antioxidant activity was studied using DPPH total antioxidant assay; cholinergic assay by Ellman's method and anti-amyloidogenic assay by thioflavin-T fluorescence and transmission electron microscopy. Results: The quantification of polyphenols was carried out following C. crista methanolic extract (CCMeOH) HPLC fingerprinting, along with LC-MS and elucidated by MS LAMPS database. GC-MS of CCMeOH was screened for potential moieties. In vitro experimental results showed that the CCMeOH was potential extract that exhibited active inhibition of antioxidant property, cholinergic enzymes acetylcholinesterase and butyrylcholinesterase. For anti-amyloidogenic evaluations, among all the extracts, the CCMeOH was found to have the potential toward inhibiting the oligomers, fibrillation of Aβ

Phytochemical composition of Caesalpinia crista extract as potential source for inhibiting cholinesterase and β-amyloid aggregation: Significance to Alzheimer's disease

Objective: To screen plant extract fractions and elucidate the components present in Caesalpinia crista (C. crista) leaves for cholinergic and anti-amyloidogenic activities for the treatment of Alzheimer's diseases.Methods: This work has been carried out to study the action of C. crista extracts from nonpolar to polar solvents toward inhibition of oxidative stress, cholinergic and amyloidosis. The antioxidant activity was studied using DPPH total antioxidant assay; cholinergic assay by Ellman's method and anti-amyloidogenic assay by thioflavin-T fluorescence and transmission electron microscopy.Results: The quantification of polyphenols was carried out following C. crista methanolic extract (CCMeOH) HPLC fingerprinting, along with LC-MS and elucidated by MS LAMPS database. GC-MS of CCMeOH was screened for potential moieties.In vitro experimental results showed that the CCMeOH was potential extract that exhibited active inhibition of antioxidant property, cholinergic enzymes acetylcholinesterase and butyrylcholinesterase. For anti-amyloidogenic evaluations, among all the extracts, the CCMeOH was found to have the potential toward inhibiting the oligomers, fibrillation of Aβ42 with good defibrillation of amyloid cascading properties.Conclusions:These results are also supported by the presence of polyphenols as the active ingredients. Multi-potent target drug therapy is a promising option in treating the Alzheimer's diseases. Methanolic extract of C. crista shows potential activity against cholinergic enzymes, Aβ42 aggregation with antioxidant activity.

Garcinexanthone G, a Selective Butyrylcholinesterase Inhibitor from the Stem Bark of Garcinia atroviridis

The present study was undertaken to investigate the isolated compounds from the stem bark of Garcinia atroviridis as potential cholinesterase inhibitors and the ligand-enzyme interactions of selected bioactive compounds in silico. The in vitro cholinesterase results showed that quercetin (3) was the most active AChE inhibitor (12.65 ± 1.57 µg/ml) while garcinexanthone G (6) was the most active BChE inhibitor (18.86 ± 2.41 µg/ml). It is noteworthy to note that compound 6 was a selective inhibitor with the selectivity index of 11.82. Molecular insight from docking interaction further substantiate that orientation of compound 6 in the catalytic site which enhanced its binding affinity as compared to other xanthones. The nature of protein-ligand interactions of compound 6 is mainly hydrogen bonding, and the hydroxyl group of compound 6 at C-10 is vital in BChE inhibition activity. Therefore, compound 6 is a notable lead for further drug design and development of BChE selective inhibitor.

Effects of energetic restriction diet on butyrylcholinesterase in obese women from southern Brazil - A longitudinal study

Objective Butyrylcholinesterase (BChE) activity has been associated with obesity, lipid concentrations, and CHE2 locus phenotypes. This, the aim of this study was to evaluate the effects of an energetic restriction diet intervention on anthropometrical and biochemical variables and on absolute and relative BChE activity in CHE2 C5+ and CHE2 C5- individuals. Subjects and methods One hundred eleven premenopausal obese women from Southern Brazil participated in an energetic restriction diet intervention (deficit of 2500 kJ/day) for 8 weeks. Their anthropometric and biochemical parameters were evaluated before and after the intervention. Plasma BChE activity was measured, and BChE bands in plasma and CHE2 locus phenotypes were detected by electrophoresis. Results The dietetic intervention decreased anthropometric and biochemical parameters as well as absolute BChE activity and relative activity of the G4 band. The CHE2 C5+ phenotype presented a different effect when compared with the CHE2 C5- phenotype. The CHE2 C5+ phenotype showed an effect in absolute BChE activity and in the relative activity of the G4 form, maintaining higher BChE activity regardless of the metabolic changes. Conclusion In our study, 8 weeks was not sufficient time to lower the body mass index to normal, but it was enough to significantly reduce the absolute BChE activity, which became similar to the levels in nonobese individuals. CHE2 C5+ individuals were resistant to the decrease in BChE activity compared to CHE2 C5- individuals. This shows that the diet did not affect the CHE2 and G4 fraction complex and that the products of the CHE2 locus in association with BChE have a role in energy metabolism, maintaining high levels of enzymatic activity even after dietary intervention.

Actividad de butirilcolinesterasa y micronúcleos en trabajadores agrícolas expuestos a mezclas de plaguicidas / Butyrylcholinesterase activity and micronuclei in agricultural workers exposed to pesticide mixtures

Los plaguicidas son xenobióticos de gran utilidad para el control de las plagas y su uso es una realidad para obtener mayor rendimiento en los cultivos. Sin embargo, tienen el riesgo de producir toxicidad, por lo que es necesario el monitoreo biológico de los trabajadores expuestos a estas sustancias. El objetivo de este estudio fue evaluar la actividad de la butirilcolinesterasa (BCh) y la presencia de micronúcleos (MN) en trabajadores expuestos a mezclas de plaguicidas en el municipio Urdaneta, estado Lara. Participaron 82 individuos de sexo masculino, 41 expuestos (GE) y 41 no expuestos (GNE), la determinación de la butirilcolinesterasa se realizó en muestras de sangre, y la de micronúcleos en muestras epiteliales de la mucosa bucal. Los resultados fueron presentados empleando estadísticos descriptivos, frecuencias absolutas y porcentajes, utilizando el paquete libre PAST v.2.04. Los valores de actividad de BCh en el GE (3528,75+/- 1162,45U/L) mostraron diferencias estadísticamente significativas (P<0,001) en relación al GNE (5764,41+/-1641,43U/L). La frecuencia de MN presentó mayor mediana en el GE respecto al GNE (3,09 vs 0,73) con una diferencia significativa (P<0,001). Al asociar el tiempo de exposición con la actividad de BCh y la frecuencia de MN, se presentó una correlación negativa con la actividad de BCh y una correlación positiva con los MN, estadísticamente significativas P<0,001 y P<0,05. Los hallazgos obtenidos reflejan que los plaguicidas fueron utilizados en forma de mezclas siendo los más usados: organofosforados, carbamatos y piretroides produciendo modificaciones en los valores de actividad de BCh y la frecuencia de MN en individuos expuestos a plaguicidas(AU)

Pesticides are xenobiotics, useful in controlling pests and their use ileads to greater crop yields. However, they carry a risk of toxicity so biological monitoring of exposed workers is necessary. The aim of this study was to evaluate the cholinesterase activity and the presence of micronuclei in workers exposed to pesticide mixtures in the town of Urdaneta, Lara. Eighty-two workers participated, 41 exposed (EG) and 41 nonexposed (NEG), all of whome were male. Blood samples were obtained for the determination of butyrylcholinesterase (BCh); buccal mucosal epithelial samples were obtained for micronuclei (MN) sampline. The results were presented as descriptive statistics, absolute frequencies and percentages, using the PAST v.2.04 a free online software package. The BCh activity values in the EG (3528.75+/-1162.45U/L) showed statistically significant differences (P<0.001) in relation to the UEG (5764.41 +/- 1641.43U/L). Median MN frequency was highest in the EG compared to UEG (3.09vs 0.73), a significant difference (P<0.001). By associating exposure time with BCh activity and MN frequency, a negative correlation was found with BCh activity and a positive correlation with MN, both statistically significant (P<0.001 and P<0.05, respectively). The results suggested pesticide mixtures were the most often used: organophosphates, carbamates and pyrethroids produced changes in the activity values of BCh and the frequency of MN in individuals exposed to pesticides(AU)

Sesquiterpenoids from the heartwood of Juniperu s chinensis

A new sesquiterpenoid, 11-hydroxy-valenc-1(10),3(4)-dien-2-one (3), two chemically synthesized but first isolate from nature, 3-oxocedran-8β-ol (1) and valenc-1(10),3(4),11(12)-trien-2-one (2) along with four known compounds, sugiol (4), (+)-nootkatone (5), 11-hydroxy-valenc-1(10)-en-2-one (6), and clovandiol (7), were isolated from the heartwood of Juniperus chinensis. All chemical structures were elucidated using extensive spectroscopic analysis including 1D and 2D NMR spectroscopy. Valenc-1(10),3(4),11(12)-trien-2-one (2) exhibited significant inhibitory activity against butyrylcholinesterase with an IC₅₀ value of 68.45 µM.

Biomarcadores inflamatórios e de estresse oxidativo em cadelas submetidas à ovário-histerectomia videoassistida ou convencional / Inflammation and oxidative stress indicators in bitches submitted to laparoscopic-assisted or conventional ovariohysterectomy

A videocirurgia é atualmente uma das principais ferramentas operatórias, com vantagens que incluem menor estresse, incisões e dor pós-operatória quando comparada aos procedimentos abertos. Objetivou-se comparar o processo inflamatório e o estresse oxidativo resultantes das técnicas de ovário-histerectomia (OVH) convencional e videoassistida, com dois portais em cadelas, por meio de hemograma, avaliação de acetilcolinesterase, butirilcolinesterase, catalase e malondialdeído séricos, imediatamente antes da operação e duas, seis, 12, 24, 48 e 72 horas após a cirurgia. Observou-se menor estresse cirúrgico nas pacientes operadas pela técnica videoassistida, e sugere-se que a técnica convencional possa implicar peroxidação lipídica, mesmo com o uso de anti-inflamatório.(AU)

Videosurgery is currently a very important surgical tool with several benefits over the open surgery, including less surgical stress, shorter incisions and less postoperative pain. The purpose of this study was to compare the inflammatory process and oxidative stress between conventional and two-port laparoscopic-assisted ovariohisterectomy (OVH) in bitches. Complete blood counting, serum acetylcholinesterase, butyrylcholinesterase, catalase and malondialdehyde were assessed on the baseline and at two, six, 12, 24, 48 and 72 hours after surgery. The patients submitted to the videoassisted technique presented lower inflammatory response. There are suggestions that the conventional technique promotes lipid peroxidation, even with the use of anti-inflammatories.(AU)

Laboratory genetic-based reference values for cholinesterase activity in a Colombian population: A step forward in personalized diagnostics / Valores de referencia basados en el contexto genético de la actividad enzimática de la colinesterasa en una población colombiana: un paso hacia el diagnóstico personalizado

Introduction: The determination of cholinesterase (ChE) activity has been commonly applied in the biomonitoring of exposure to organophosphate and carbamate pesticides. However, ChE activity is influenced by genetic factors. Integrating genotype and phenotype information in clinical laboratory tests would increase the accuracy of the reference values in well-defined populations. Objective: To establish genetic-based reference values for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activity in a Colombian population. Materials and methods: A total of 397 healthy adults from Bucaramanga were included in the study. AChE and BChE activities were measured in blood samples by potentiometry and spectrophotometry, respectively. Genotyping for ACHE rs17880573 and BCHE rs1803274 was performed using the TaqMan allelic discrimination assay. The statistical analyses to obtain the reference values were performed with the MedCalc® software. Results: Allele frequencies were 10.58% for rs17880573 A and 8.82% for rs1803274 A. People with genotypes rs1803274 AA and AG showed a reduction of 20.69% and 10.92% respectively in mean BChE activity compared to people with genotype GG. No significant differences were identified in AChE activity between rs17880573 alleles or genotypes. In the overall sample, the corresponding reference values were as follows: for AChE activity, 0.62-0.98 D pH/h and for BChE activity, 4796.3-10321.1 U/L for people carrying the allele rs1803274A and 5768.2-11180.4 U/L for people carrying the genotype rs1803274 GG. Conclusion: We strongly recommend using these genetic-based reference values for ChE enzymes in our well-defined population in daily clinical practice.

Introducción. La determinación de la actividad enzimática de la colinesterasa se utiliza comúnmente en la vigilancia biológica de la exposición a pesticidas organofosforados y carbamatos. Sin embargo, los factores genéticos afectan la actividad de la colinesterasa, por lo que la integración de la información sobre genotipos y fenotipos en las pruebas de laboratorio clínico, incrementaría la precisión de los valores de referencia. Objetivo. Establecer los valores de referencia basados en el contexto genético para la actividad enzimática de la acetilcolinesterasa (AChE) y la butirilcolinesterasa (BChE), en una población colombiana. Materiales y métodos. Se incluyeron 397 adultos sanos. La actividad de la acetilcolinesterasa y la de la butirilcolinesterasa, se determinaron en muestras de sangre por potenciometría y espectrofotometría, respectivamente. Los genotipos de los ACHE rs17880573 y BCHE rs1803274 se obtuvieron mediante el ensayo TaqMan y los valores de referencia se estimaron con el programa MedCalc®. Resultados. La frecuencia alélica fue de 10,58 % para rs17880573 A y de 8,82 % para rs1803274 A. Las personas con los genotipos rs1803274 AA y AG, mostraron una reducción en el promedio de la actividad de la butirilcolinesterasa de 20,69 % y de 10,92 %, respectivamente, comparados con aquellas con el genotipo GG. No se encontraron diferencias significativas en la actividad de la acetilcolinesterasa con respecto a los alelos y genotipos del rs17880573. Los valores de referencia determinados para esta población fueron de 0,62-0,98 D pH/h para acetilcolinesterasa y de 4796,3-10321,1 U/L para butirilcolinesterasa, en las personas portadoras del alelo rs1803274 A, y de 5768,2-11180,4 U/L, en las portadoras del genotipo rs1803274 GG. Conclusión. Se recomienda el uso de estos valores de referencia basados en el contexto genético para las colinesterasas, en la práctica clínica diaria en esta población.