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1.
Sci Rep ; 11(1): 16687, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404888

RESUMO

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.


Assuntos
Acetilcolinesterase/sangue , Anestesia Geral , Butirilcolinesterase/sangue , Doenças Vasculares/cirurgia , Adulto , Idoso , Feminino , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Vasculares/sangue
2.
Molecules ; 26(13)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206601

RESUMO

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.


Assuntos
Butirilcolinesterase/sangue , Agentes Neurotóxicos , Organofosfatos , Plasma , Biomarcadores/sangue , Inibidores da Colinesterase/farmacocinética , Inibidores da Colinesterase/toxicidade , Humanos , Agentes Neurotóxicos/farmacocinética , Agentes Neurotóxicos/toxicidade , Organofosfatos/farmacocinética , Organofosfatos/toxicidade
3.
Toxicology ; 452: 152719, 2021 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-33592259

RESUMO

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.


Assuntos
Butirilcolinesterase/sangue , Inibidores da Colinesterase/toxicidade , Agentes Neurotóxicos/toxicidade , Organofosfatos/toxicidade , Oximas/farmacologia , Compostos de Piridínio/farmacologia , Animais , Cobaias , Humanos , Oximas/química , Compostos de Piridínio/química , Ratos
4.
Chem Biol Interact ; 338: 109287, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33129804

RESUMO

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.


Assuntos
Acetilcolinesterase/sangue , Encéfalo/enzimologia , Encéfalo/patologia , Butirilcolinesterase/sangue , Dano ao DNA , Neonicotinoides/administração & dosagem , Nitrocompostos/administração & dosagem , Estresse Oxidativo , Acetilcolinesterase/metabolismo , Administração Oral , Animais , Biomarcadores/metabolismo , Peso Corporal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Butirilcolinesterase/metabolismo , Catalase/metabolismo , Ensaio Cometa , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo
5.
Nat Prod Res ; 35(10): 1722-1726, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-31215236

RESUMO

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).


Assuntos
Antibacterianos/farmacologia , Antioxidantes/farmacologia , Inibidores da Colinesterase/farmacologia , Linaria/química , Acetilcolinesterase/metabolismo , Argélia , Animais , Antioxidantes/química , Butirilcolinesterase/sangue , Inibidores da Colinesterase/química , Electrophorus , Cavalos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Staphylococcus aureus/efeitos dos fármacos
6.
Environ Toxicol Pharmacol ; 82: 103558, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33307127

RESUMO

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.


Assuntos
Bufo marinus , Poluentes da Água/toxicidade , Animais , Apoptose , Biomarcadores/sangue , Butirilcolinesterase/sangue , Eritrócitos/efeitos dos fármacos , Feminino , Glutationa Transferase/sangue , Masculino , Malondialdeído/sangue , México , Sintase do Porfobilinogênio/sangue , Rios
7.
J Cancer Res Ther ; 16(Supplement): S39-S42, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33380649

RESUMO

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.


Assuntos
Biomarcadores Tumorais/sangue , Butirilcolinesterase/sangue , Neoplasias Bucais/diagnóstico , Recidiva Local de Neoplasia/epidemiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Adulto , Biomarcadores Tumorais/economia , Butirilcolinesterase/economia , Estudos de Casos e Controles , Intervalo Livre de Doença , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/patologia , Mucosa Bucal/efeitos da radiação , Mucosa Bucal/cirurgia , Neoplasias Bucais/sangue , Neoplasias Bucais/mortalidade , Neoplasias Bucais/terapia , Período Pós-Operatório , Período Pré-Operatório , Prognóstico , Radioterapia Adjuvante , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia
8.
Anal Chem ; 92(21): 14806-14813, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33058681

RESUMO

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.


Assuntos
Técnicas Biossensoriais/instrumentação , Butirilcolinesterase/metabolismo , Ferrocianetos/química , Ferro/química , Compostos Organometálicos/química , Testes Imediatos , Temperatura , Butirilcolinesterase/sangue , Humanos , Limite de Detecção
9.
Chem Biol Interact ; 330: 109225, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32795450

RESUMO

Two types of cholinesterases (ChEs) are present in mammalian blood and tissues: acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). While AChE regulates neurotransmission by hydrolyzing acetylcholine at the postsynaptic membranes and neuromuscular junctions, BChE in plasma has been suggested to be involved in detoxifying toxic compounds. This study was undertaken to establish the identity of circulating ChE activity in plasmas from domestic animals (bovine, ovine, caprine, porcine and equine) by assessing sensitivity to AChE-specific inhibitors (BW284c51 and edrophonium) and BChE-specific inhibitors (dibucaine, ethopropazine and Iso-OMPA) as well as binding to anti-FBS AChE monoclonal antibodies (MAbs). Based on the inhibition of ChE activity by ChE-specific inhibitors, it was determined that bovine, ovine and caprine plasma predominantly contain AChE, while porcine and equine plasma contain BChE. Three of the anti-FBS AChE MAbs, 4E5, 5E8 and 6H9, inhibited 85-98% of enzyme activity in bovine, ovine and caprine plasma, confirming that the esterase in these plasmas was AChE. These MAbs did not bind to purified recombinant human or mouse AChE, demonstrating that these MAbs were specific for AChEs from ruminant species. These MAbs did not inhibit the activity of purified human BChE, or ChE activity in porcine and equine plasma, confirming that the ChE in these plasmas was BChE. Taken together, these results demonstrate that anti-FBS AChE MAbs can serve as useful tools for distinguishing between AChEs from ruminant and non-ruminant species and BChEs.


Assuntos
Acetilcolinesterase/imunologia , Anticorpos Monoclonais/sangue , Butirilcolinesterase/imunologia , Acetilcolinesterase/sangue , Animais , Animais Domésticos/imunologia , Butirilcolinesterase/sangue , Bovinos , Inibidores da Colinesterase/metabolismo , Inibidores da Colinesterase/farmacologia , Sangue Fetal/imunologia , Humanos , Camundongos , Ruminantes/imunologia
10.
Analyst ; 145(12): 4305-4313, 2020 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-32478771

RESUMO

An increasing number of patients are living with Alzheimer's disease (AD); thus, the need for a method to detect AD early and sensitively has become urgent, and the demand for an intelligent analytical platform is growing year by year. Abnormal levels of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are known to be indicative of AD. In this work, a novel conjugated polythiophene (CP) compound was successfully combined with CdTe quantum dots (QDs) to improve their selectivity and sensitivity. The QDs successfully enabled the detection of low concentrations of AChE by turning on the fluorescence of the CdTe/CP via the interaction between CP and thiocholine produced by ATCh hydrolysis and aggregation induced emission enhancement (AIEE). Under optimal conditions, we reached a low detection limit of 0.14 U L-1, which is 7.9 times lower than that of pristine QDs. More importantly, an efficient, inexpensive, and disposable paper-based platform, which allows the efficient visual detection of AChE activity via the color variation of CdTe/CP, was designed. Moreover, the accuracy of the method was demonstrated by conducting a recovery test in human serum, in which the recoveries reached 107% and 110%, proving that CdTe/CP has considerable potential to be used for analyzing real biological samples. The advantages of this method are its simplicity, fast detection capability, affordability, and the fact that it can be used for on-site detection of AChE activity. Furthermore, it has certain guiding significance for detecting AD.


Assuntos
Acetilcolinesterase/sangue , Butirilcolinesterase/sangue , Ensaios Enzimáticos/métodos , Papel , Pontos Quânticos/química , Compostos de Cádmio/química , Ensaios Enzimáticos/instrumentação , Humanos , Dispositivos Lab-On-A-Chip , Limite de Detecção , Masculino , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodos , Polímeros/síntese química , Polímeros/química , Telúrio/química , Tiofenos/síntese química , Tiofenos/química
11.
Arch Toxicol ; 94(6): 2239-2247, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32303803

RESUMO

Suicidal ingestion of organophosphorus (OP) or carbamate (CM) compounds challenges health care systems worldwide, particularly in Southeast Asia. The diagnosis and treatment of OP or CM poisoning is traditionally based on the clinical appearance of the typical cholinergic toxidrome, e.g. miosis, salivation and bradycardia. Yet, clinical signs might be inconclusive or even misleading. A current case report highlights the importance of enzymatic assays to provide rapid information and support clinicians in diagnosis and rational clinical decision making. Furthermore, the differentiation between OP and CM poisoning seems important, as an oxime therapy will most probably not provide benefit in CM poisoning, but-as every pharmaceutical product-it might result in adverse effects. The early identification of the causing agent and the amount taken up in the body are helpful in planning of the therapeutic regimen including experimental strategies, e.g. the use of human blood products to facilitate scavenging of the toxic agent. Furthermore, the analysis of biotransformation products and antidote levels provides additional insights into the pathophysiology of OP or CM poisoning. In conclusion, cholinesterase activities and modern analytical methods help to provide a more effective treatment and a thorough understanding of individual cases of OP or CM poisoning.


Assuntos
Acetilcolinesterase/sangue , Butirilcolinesterase/sangue , Inibidores da Colinesterase/envenenamento , Ensaios Enzimáticos Clínicos , Intoxicação por Organofosfatos/diagnóstico , Idoso de 80 Anos ou mais , Antídotos/uso terapêutico , Atropina/uso terapêutico , Biomarcadores/sangue , Reativadores da Colinesterase/uso terapêutico , Tomada de Decisão Clínica , Diagnóstico Diferencial , Proteínas Ligadas por GPI/sangue , Humanos , Antagonistas Muscarínicos/uso terapêutico , Cloreto de Obidoxima/uso terapêutico , Intoxicação por Organofosfatos/sangue , Intoxicação por Organofosfatos/tratamento farmacológico , Valor Preditivo dos Testes , Tentativa de Suicídio , Resultado do Tratamento
12.
Neurotoxicology ; 77: 216-230, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32006538

RESUMO

Chronic occupational exposure to organophosphorus pesticides (OPs) is consistently associated with deficits on behavioral tests when compared to unexposed comparison groups. However, a dose-response relationship has yet to be established, leading some to doubt an association between occupational OP exposure and behavioral deficits. Pesticide application teams in Egypt who are primarily exposed to one OP, chlorpyrifos (CPF), were recruited into a field assessment. Trail Making A and the more challenging Trail Making B tests were administered to 54 engineers (who supervise the pesticide application process, usually from the side of the field), 59 technicians (who guide the pesticide applicators in the field), 31 applicators (who mix and apply pesticides using knapsack sprayers), and 150 controls (who did not work in the fields) at two different times during the OP application season as well as immediately after applications had ended and 1.5 months later. All participants were males since only males work on pesticide application teams in Egypt. Urinary levels of 3,5,6-trichloro-2-pyridinol (TCPy), a specific metabolite of CPF, confirmed the pattern of lower to higher CPF exposures from engineers to technicians to applicators, and these were all greater than urinary metabolite levels in controls. A consistent relationship between job title and performance speed on the behavioral task was observed: Controls had the best (fastest) performance on Trail Making A and B tests throughout the application season, and applicators had significantly slower performance than engineers on Trail Making A (p = 0.015) and B (p = 0.003). However, individual urinary TCPy, blood acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) levels did not predict individual performance. This study identifies a dose-related effect based on job title, which serves as a surrogate for chronic exposure in that differing job titles exhibit varying group exposure levels. The results establish that chronic occupational exposure to chlorpyrifos is neurotoxic and suggest that the classic biomarkers of recent CPF exposure are not predictive of chronic exposure effects.


Assuntos
Atenção/efeitos dos fármacos , Clorpirifos/toxicidade , Função Executiva/efeitos dos fármacos , Exposição Ocupacional/efeitos adversos , Praguicidas/toxicidade , Acetilcolinesterase/sangue , Butirilcolinesterase/sangue , Egito , Humanos , Masculino , Testes Neuropsicológicos , Piridonas/urina
13.
Parasitol Int ; 76: 102066, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32006676

RESUMO

Trypanosoma cruzi infection triggers an intense production of pro-inflammatory cytokines mediated by T helper 1 lymphocytes, inducing the anti-inflammatory reflex of acetylcholine (ACh). The ACh concentration modulation is associated to the two major esterases, the acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). AChE H353N protein polymorphism is related to low Chagas chronic disease prognostic. In order to evaluate the correlation of plasmatic BuChE concentration and the presence of AChE H353N polymorphism in Chagas disease patients and healthy individuals, we studied two groups of individuals, one of 61 Chagas disease patients and another of 74 healthy individuals. Plasma concentration of BuChE was measured by the chemiluminescent method and AChE H353N polymorphism was investigated by PCR-RFLP and sequencing of the respective encoding AChE gene fragment. The BuChE concentration was statistically higher in Chagas disease patients, with no AChE genotype significant influence. AChE genotypes YT*A/YT*A, YT*A/YT*B and YT*B/YT*B, respectively, were expressed in 53 (86.88%), 7 (11.46%) and one (1.64%) chagasic patients, and in 68 (91.89%), 6 (8.10%) and none healthy individuals. BuChE activity may represent an important marker for chronic Chagas disease inflammatory process and prognostic. Lower BuChE concentration correlated with AChE YT*B allele, although without statistical power.


Assuntos
Acetilcolinesterase/genética , Butirilcolinesterase/sangue , Doença de Chagas/enzimologia , Inflamação , Polimorfismo Genético , Adulto , Idoso , Alelos , Biomarcadores/sangue , Doença de Chagas/genética , Doença Crônica , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem
14.
BMJ Open ; 10(1): e031212, 2020 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-31941763

RESUMO

OBJECTIVES: Postoperative delirium (POD) is a common complication after elective cardiac surgery. Recent evidence indicates that a disruption in the normal activity of the cholinergic system may be associated with delirium. DESIGN: Prospective observational study. SETTING: Single-centre at a European academic hospital. PRIMARY AND SECONDARY OUTCOME MEASURES: In our study the enzyme activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were determined preoperatively as well as on the first and second postoperative day. The confusion assessment method for the intensive care unit was used to screen patients for the presence of POD. RESULTS: A total of 114 patients were included in the study. POD was associated with a decrease in BChE activity on postoperative day 1 (p=0.03). In addition, patients who developed POD, had significantly lower preoperative AChE activity than patients without POD (p<0.01). Multivariate analysis identified a preoperatively decreased AChE activity (OR 3.1; 95% CI 1.14 to 8.46), anticholinergic treatment (OR 5.09; 95% CI 1.51 to 17.23), elevated European System for Cardiac Operative Risk Evaluation (OR 3.68; 95% CI 1.04 to 12.99) and age (OR 3.02; 95% CI 1.06 to 8.62) to be independently associated with the development of POD. CONCLUSIONS: We conclude that a reduction in the acetylcholine hydrolysing enzyme activity in patients undergoing cardiac surgery may correlate with the development of POD.


Assuntos
Butirilcolinesterase/sangue , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Delírio/enzimologia , Complicações Pós-Operatórias/enzimologia , Idoso , Biomarcadores/sangue , Delírio/epidemiologia , Delírio/etiologia , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Fatores de Risco
15.
Biotechnol Bioeng ; 117(1): 157-166, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31544955

RESUMO

Chinese hamster ovary (CHO) cells typically produce glycoproteins with N-glycans terminating in α-2,3 sialylation. Human cells produce glycoproteins that include α-2,3 and α-2,6 sialic acids. To examine the impact of altering protein sialylation on pharmacokinetic properties, recombinant human butyrylcholinesterase (BChE) was produced in CHO cells by knocking out the α-2,3 sialyltransferase genes followed by overexpression of the α-2,6 sialyltransferase (26BChE) enzyme. The N-glycan composition of 26BChE was compared to BChE with α-2,3 sialylation (23BChE) derived from wild-type CHO cells. Both 23BChE and 26BChE exhibited comparable antennarity distributions with bi-antennary di-sialylated glycans representing the most abundant glycoform. CD-1 mice were intravenously injected with the 23BChE or 26BChE, and residual BChE activities from blood collected at various time points for pharmacokinetic analyses. Although 23BChE contained a slightly lower initial sialylation level compared to 26BChE, the molecule exhibited higher residual activity between 5 and 24 hr postinjection. Pharmacokinetic analyses indicated that 23BChE exhibited an increase in area under the curve and a lower volume of distribution at steady state than that of 26BChE. These findings suggest that the type of sialylation linkage may play a significant role in the pharmacokinetic behavior of a biotherapeutic when tested in in vivo animal models.


Assuntos
Butirilcolinesterase/química , Butirilcolinesterase/farmacocinética , Ácido N-Acetilneuramínico/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/farmacocinética , Animais , Butirilcolinesterase/sangue , Butirilcolinesterase/genética , Células CHO , Cricetinae , Cricetulus , Humanos , Camundongos , Proteínas Recombinantes/sangue , Proteínas Recombinantes/genética
16.
Biochem Pharmacol ; 171: 113670, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31628910

RESUMO

Human butyrylcholinesterase (E.C. 3.1.1.8) purified from blood plasma has previously been shown to provide protection against up to five and a half times the median lethal dose of an organophosphorus nerve agent in several animal models. In this study the stoichiometric nature of the protection afforded by human butyrylcholinesterase against organophosphorus nerve agents was investigated in guinea pigs. Animals were administered human butyrylcholinesterase (26.15 mg/kg ≡ 308 nmol/kg) by the intravascular or intramuscular route. Animals were subsequently dosed with either soman or VX in accordance with a stage-wise adaptive dose design to estimate the modified median lethal dose in treated animals. Human butyrylcholinesterase (308 nmol/kg) increased the median lethal dose of soman from 154 nmol/kg to 770 nmol/kg. Comparing the molar ratio of agent molecules to enzyme active sites yielded a stoichiometric protective ratio of 2:1 for soman, likely related to the similar stereoselectivity the enzyme has compared to the toxic target, acetylcholinesterase. In contrast, human butyrylcholinesterase (308 nmol/kg) increased the median lethal dose of VX from 30 nmol/kg to 312 nmol/kg, resulting in a stoichiometric protective ratio of only 1:1, suggesting a lack of stereoselectivity for this agent.


Assuntos
Butirilcolinesterase/administração & dosagem , Substâncias para a Guerra Química/envenenamento , Agentes Neurotóxicos/envenenamento , Envenenamento/prevenção & controle , Animais , Área Sob a Curva , Butirilcolinesterase/sangue , Butirilcolinesterase/química , Substâncias para a Guerra Química/química , Cobaias , Humanos , Injeções Intramusculares , Injeções Intravenosas , Dose Letal Mediana , Masculino , Taxa de Depuração Metabólica , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacocinética , Compostos Organotiofosforados/química , Compostos Organotiofosforados/envenenamento , Soman/química , Soman/envenenamento , Estereoisomerismo
17.
J Environ Sci Health B ; 55(4): 355-360, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31868080

RESUMO

The aim of this study was to evaluate the DNA damage in soybean growers during two agricultural periods of a crop season (high and low exposure) and a control group, as well as butyrylcholinesterase (BChE) activity during these exposure periods in order to estimate the degree of BChE inhibition for the exposed group. DNA damage in peripheral whole blood was evaluated by the comet assay and plasma BChE activity was accessed as a measure of exposure to cholinesterase inhibitors. None of the soybean growers reported using full Personal Protective Equipment (PPE). BChE was lower in high exposure period than in low exposure period and DNA damage index was significantly increased in the high exposure period than in the low exposure period. In addition, DNA damage in both exposure periods was higher than control group. No correlation was found between exposure time and DNA damage and BChE activity. However, negative correlation was observed between DNA damage in high and low exposure periods. The results indicate that soybean growers are exposed to cholinesterase inhibitors and to pesticides mixtures with genotoxic potential.


Assuntos
Butirilcolinesterase/sangue , Dano ao DNA , Fazendeiros , Exposição Ocupacional/análise , Praguicidas/toxicidade , Soja , Adulto , Agricultura , Brasil , Estudos de Casos e Controles , Inibidores da Colinesterase/toxicidade , Ensaio Cometa , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
18.
Vet Clin Pathol ; 48(4): 740-747, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31789474

RESUMO

BACKGROUND: Sepsis is a complex syndrome that involves an increased oxidative stress status and dysregulation of cholinergic neurotransmission. Paraoxonase-1 (PON-1) and butyrylcholinesterase (BChE) activities have been identified as significant biomarkers to monitor such disorders in human septic patients. OBJECTIVE: We aimed to determine the diagnostic and prognostic value of PON-1 and BChE vs other traditional acute-phase proteins such as albumin (ALB) and C-reactive protein (CRP) in septic dogs. METHODS: This prospective observational study included 20 dogs with a diagnosis of sepsis, 27 with low-grade systemic inflammation (LGSI), and 10 healthy dogs that served as controls. Plasma samples were obtained from all dogs for analysis on admission, and then every 24-48 hours until discharge or death in the septic group. RESULTS: Dogs with sepsis had lower PON-1 activity compared with dogs in the LGSI group (1.1 ± 0.10 vs 1.6 ± 0.08 U/mL, P = .002), but no differences in BChE activity were detected between the groups. PON-1, ALB, and CRP could successfully discriminate healthy animals from those with sepsis looking at the area under the curve (AUC) of the receiver operator characteristics curves (ROCs), which were 0.828, 0.903 and 1.000, respectively. Finally, although no differences were found among the groups for PON-1 or BChE activity, the nonsurvivor septic dogs had higher CRP (P = .002), lower ALB (P = .025) levels, and tended to have lower PON-1 (P = .082) activities than the survivors at patient death or discharge. CONCLUSION: Septic dogs showed lower plasma PON-1 and higher BChE activities, but only PON-1 activity correlated with disease severity. Further studies are warranted to describe the usefulness of these new biomarkers of sepsis progression and recovery in dogs.


Assuntos
Proteínas de Fase Aguda/metabolismo , Arildialquilfosfatase/sangue , Butirilcolinesterase/sangue , Doenças do Cão/sangue , Sepse/veterinária , Animais , Biomarcadores/sangue , Doenças do Cão/diagnóstico , Cães , Feminino , Inflamação/sangue , Inflamação/veterinária , Masculino , Prognóstico , Estudos Prospectivos , Sepse/sangue , Sepse/diagnóstico
19.
Anal Chem ; 91(24): 15866-15872, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31756075

RESUMO

The combination of gold nanoclusters (AuNCs) and nanomaterial-based quencher creates an innovative method for sensors design. In this work, we report a fluorescent sensing platform for sensitive detection of butyrylcholinesterase (BChE). The fluorescence of AuNCs can be quenched by iron oxyhydroxide (FeOOH) nanomaterials. In the presence of BChE and acetylthiocholine (ATCh), nano-FeOOH can be effectively decomposed by the enzymatic hydrolysate (thiocholine), leading to the recovery of AuNCs fluorescence. The Au/FeOOH exhibits the highest fluorescence quenching efficiency compared with other transition metal oxyhydroxide-based sensing systems, e.g., Au/CoOOH and Au/NiOOH. The corresponding fluorescence recovery efficiency is also the best for Au/FeOOH. The large surface area of nanomaterials and thin nanostructure provide a favorable platform for the reaction of enzymatic hydrolysate and eventually improve the high sensitivity of the probe. A linear detection range for BChE is achieved within 5-100 ng mL-1 along with a detection limit of 4 ng mL-1. By taking advantage of the high sensitivity, the Au/FeOOH was successfully used for BChE quantification in 2 µL of finger blood.


Assuntos
Butirilcolinesterase/análise , Compostos Férricos/química , Ouro/química , Nanopartículas Metálicas/química , Espectrometria de Fluorescência/métodos , Butirilcolinesterase/sangue , Humanos , Limite de Detecção , Nanoestruturas/química , Reprodutibilidade dos Testes
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