Cholinesterases/genetics* ; Dimethoate/analogs & derivatives* ; Humans ; Occupational Exposure/adverse effects* ; Polymorphism, Genetic ; Telomere

Alzheimer's disease is a chronic neurodegenerative disorder with no curative treatment. The commercially available drugs, which target acetylcholinesterase, are not satisfactory. The aim of this study was to investigate the cholinesterase inhibitory activity of Solenostemma argel aerial part. Eight compounds were isolated and identified by NMR: kaempferol-3-O-glucopyranoside (1), kaempferol (2), kaempferol-3-glucopyranosyl(1→6)rhamnopyranose (3) p-hydroxybenzoic acid (4), dehydrovomifoliol (5), 14,15-dihydroxypregn-4-ene-3,20-dione (6), 14,15-dihydroxy-pregn-4-ene-3,20-dione-15β-D-glucopyranoside (7) and solargin I (8). Two of them (compounds 2 and 3) could inhibit over 50 % of butyrylcholinesterase activity at 100 µM. Compound (2) displayed the highest inhibitory effect against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with a slight selectivity towards the latter. Molecular docking studies supported the in vitro results and revealed that (2) had made several hydrogen and π-π stacking interactions which could explain the compound potency to inhibit AChE and BChE.
Acetylcholinesterase ; Alzheimer Disease ; Butyrylcholinesterase ; Cholinesterases ; Hydrogen ; In Vitro Techniques ; Neurodegenerative Diseases

BACKGROUND: The reversal of a neuromuscular blockade has typically been achieved with a cholinesterase inhibitor and the concomitant use of an anticholinergic agent, and this remains a popular method. Since the introduction of sugammadex in the market, its use has been increasing because of the rapid recovery from a neuromuscular blockade achieved by rocuronium. The occurrence of anaphylaxis or an anaphylactic reaction resulting from sugammadex is rare and has been reported sparsely. Thus, one may not recognize the possibility of sugammadex-induced hypersensitivity when sudden life-threatening hypotension occurs, especially without skin manifestations during the emergence of anesthesia. This may delay treatment and increase morbidity. CASE: We report a case of a sugammadex-related hypersensitivity reaction which manifested as pure cardiovascular collapse during the emergence of anesthesia. CONCLUSIONS: We emphasize that vigilance should be paid for at least five minutes following sugammadex administration in daily clinical practice.
Anaphylaxis ; Anesthesia ; Cholinesterases ; Hypersensitivity ; Hypotension ; Methods ; Neuromuscular Blockade ; Skin Manifestations

OBJECTIVE: In severe organophosphate (OP) poisoning, administration of atropine via continuous intravenous infusion is typically considered. To date, there have been no studies on predicting successful atropine discontinuation through plasma cholinesterase (PChE) and serum lactate levels, which are monitored during critical care in severe acute OP poisoning. Therefore, we retrospectively evaluated the usefulness of serum lactate and PChE as predictors of successful discontinuation of atropine infusion. METHODS: This retrospective observational study was performed on consecutive adult patients treated for severe acute OP poisoning between March 2011 and December 2016. We sequentially evaluated serum lactate and PChE levels on emergency department arrival and before a discontinuation trial of atropine infusion. Discontinuation of atropine intravenous infusion was attempted in patients after clearance of respiratory secretions and cessation of bronchoconstriction. Discontinuation of atropine infusion attempts were divided into successful and failed trials. RESULTS: A total of 95 trials were conducted in 62 patients. Serum lactate levels before trials were significantly different between patients with successful and failed trials. The area under the curve for prediction of successful atropine discontinuation using serum lactate levels before trial discontinuation were 0.742 (95% confidence interval, 0.638 to 0.846). PChE level was not significantly different between two groups. CONCLUSION: Serum lactate levels before the discontinuation trial of atropine infusion served to predict successful discontinuation in severe acute OP poisoning.
Adult ; Atropine* ; Bronchoconstriction ; Cholinesterases ; Critical Care ; Emergency Service, Hospital ; Humans ; Infusions, Intravenous ; Lactic Acid* ; Observational Study ; Organophosphate Poisoning* ; Plasma ; Poisoning ; Prognosis ; Retrospective Studies

PURPOSE: Organophosphates, commonly used in agricultural pesticides, pose high risks and incidences of poisoning. In the present study, we investigated the relative risk and clinical severity, including laboratory results, of non-oral route poisoning (NORP) patients, compared to oral route poisoning (ORP) patients. MATERIALS AND METHODS: A single institutional toxicology database registry was utilized to gain information on clinical laboratory results on organophosphate poisoning patients who visited the emergency department (ED) between January 2000 and October 2016. Clinical outcomes, such as mortality and complication rates, were compared using 1:2 propensity score matching in the total cohort. RESULTS: Among a total of 273 patients in our study, 34 experienced NORP. After 1:2 propensity score matching, rates of respiratory complications and mortality were higher in the ORP group than in the NORP group. However, there was no difference in hospitalization time and time spent in the intensive care unit between the two groups. Compared with ORP patients after matching, the relative risk of mortality in NORP patients was 0.34, and the risk of respiratory distress was 0.47. The mean level of pseudocholinesterase was significantly higher in the NORP group than in the ORP group, while recovery rates were similar between the two groups. CONCLUSION: Although the majority of NORP patients were admitted to the ED with unintentional poisoning and the relative risk of NORP was lower than that for ORP, we concluded that NORP is as critical as ORP. Considerable medical observation and intensive therapeutic approaches are also needed for NORP patients.
Cholinesterases ; Cohort Studies ; Emergency Service, Hospital ; Hospitalization ; Humans ; Incidence ; Intensive Care Units ; Mortality ; Organophosphate Poisoning* ; Organophosphates ; Pesticides ; Poisoning* ; Propensity Score ; Pseudocholinesterase ; Toxicology

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.
Butyrylcholinesterase ; Catalytic Domain ; Cholinesterase Inhibitors ; Cholinesterases ; Computer Simulation ; Drug Design ; Garcinia ; Hydrogen Bonding ; In Vitro Techniques ; Quercetin ; Xanthones

The three flavone glycosides, 4′-O-methylisoscutellarein 7-O-(6‴-O-acetyl)-β-D-allopyranosyl(1→2)-β-D-glucopyranoside (1), isoscutellarein 7-O-(6‴-O-acetyl)-β-D-allopyranosyl(1→2)-β-D-glucopyranoside (3), and isoscutellarein 7-O-β-D-allopyranosyl(1→2)-β-D-glucopyranoside (4) in addition to a flavonol glycoside, kaempferol 3-O-β-D-glucopyranoside (astragalin, 2), were isolated from Stachys japonica (Lamiaceae). In cholinesterase inhibition assay, compound 1 significantly inhibited aceylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities (IC₅₀s, 39.94 µg/ml for AChE and 86.98 µg/ml for BChE). The content of isolated compounds were evaluated in this plant extract by HPLC analysis. Our experimental results suggest that the flavonoid glycosides of S. japonica could prevent the memory impairment of Alzheimer's disease.
Alzheimer Disease ; Butyrylcholinesterase ; Cholinesterases ; Chromatography, High Pressure Liquid ; Glycosides ; Lamiaceae ; Memory ; Plants ; Stachys

Pneumatosis cystoides intestinalis and portomesenteric venous gas are uncommon radiological findings, but are found commonly in cases of bowel ischemia, or as a result of various non-ischemic conditions. A 72-year-old man visited an emergency center with altered mental status 2 hours after ingestion of an unknown pesticide. On physical examination, he showed the characteristic hydrocarbon or garlic-like odor, miotic pupils with no response to light, rhinorrhea, shallow respiration, bronchorrhea, and sweating over his face, chest and abdomen. Laboratory results revealed decreased serum cholinesterase, as well as elevated amylase and lipase level. We made the clinical diagnosis of organophosphate poisoning in this patient based on the clinical features, duration of symptoms and signs, and level of serum cholinesterase. Activated charcoal, fluid, and antidotes were administered after gastric lavage. A computerized tomography scan of the abdomen with intravenous contrast showed acute pancreatitis, poor enhancement of the small bowel, pneumatosis cystoides intestinalis, portomesenteric venous gas and ascites. Emergent laparotomy could not be performed because of his poor physical condition and refusal of treatment by his family. The possible mechanisms were believed to be direct intestinal mucosal damage by pancreatic enzymes and secondary mucosal disruption due to bowel ischemia caused by shock and the use of inotropics. Physicians should be warned about the possibility of pneumatosis cystoides intestinalis and portomesenteric venous gas as a complication of pancreatitis following anticholinesterase poisoning.
Abdomen ; Aged ; Amylases ; Antidotes ; Ascites ; Charcoal ; Cholinesterases ; Diagnosis ; Eating ; Emergencies ; Gastric Lavage ; Humans ; Ischemia ; Laparotomy ; Lipase ; Odors ; Organophosphate Poisoning ; Pancreatitis ; Physical Examination ; Pneumatosis Cystoides Intestinalis ; Poisoning* ; Pupil ; Respiration ; Shock ; Sweat ; Sweating ; Thorax ; Treatment Refusal

Neuromuscular blockade plays an important role in the safe management of patient airways, surgical field improvement, and respiratory care. Rapid-sequence induction of anesthesia is indispensable to emergency surgery and obstetric anesthesia, and its purpose is to obtain a stable airway, adequate depth of anesthesia, and appropriate respiration within a short period of time without causing irritation or damage to the patient. There has been a continued search for new neuromuscular blocking drugs (NMBDs) with a rapid onset of action. Factors that affect the onset time include the potency of the NMBDs, the rate of NMBDs reaching the effect site, the onset time by dose control, metabolism and elimination of NMBDs, buffered diffusion to the effect site, nicotinic acetylcholine receptor subunit affinity, drugs that affect acetylcholine (ACh) production and release at the neuromuscular junction, drugs that inhibit plasma cholinesterase, presynaptic receptors responsible for ACh release at the neuromuscular junction, anesthetics or drugs that affect muscle contractility, site and methods for monitoring neuromuscular function, individual variability, and coexisting disease. NMBDs with rapid onset without major adverse events are expected in the next few years, and the development of lower potency NMBDs will continue. Anesthesiologists should be aware of the use of NMBDs in the management of anesthesia. The choice of NMBD and determination of the appropriate dosage to modulate neuromuscular blockade characteristics such as onset time and duration of neuromuscular blockade should be considered along with factors that affect the effects of the NMBDs. In this review, we discuss the factors that affect the onset time of NMBDs.
Acetylcholine ; Anesthesia ; Anesthesia, Obstetrical ; Anesthetics ; Cholinesterases ; Diffusion ; Drug Interactions ; Emergencies ; Humans ; Metabolism ; Neuromuscular Blockade* ; Neuromuscular Blocking Agents* ; Neuromuscular Junction ; Neuromuscular Monitoring ; Pharmacokinetics ; Plasma ; Receptors, Nicotinic ; Receptors, Presynaptic ; Respiration

OBJECTIVETo observe the effect of sodium bicarbonate combined with ulinastatin on cholinesterase activity for patients with acute phoxim pesticide poisoning.

METHODSA total of 67 eligible patients with acute phoxim pesticide poisoning, Who were admitted to the emeryency department of hospital from March 2011 to February 2014, Acording to different treatments au patients were randomly divided into the conventional treatment group (n=34) and the sodium bicarbonate+ulinastatin group (n=35) . The conventional treatment group were given thorough gastric lavage with water, the sodium bicarbonate + ulinastatin group were given gastric lavage with 2% sodium bicarbonate solution. Both groups were given such treatments as catharsis, administration of oxygen, fluid infusion, diuresis, and antidotes such as atropine and pralidoxime methylchloride. On the basis of comprehensive treatment, people in the sodium bicarbonate+ulinastatin group were given 5% sodium bicarbonate injection and ulinastatin. The clinical effect of the two groups were compared.

RESULTSThe serum cholinesterase activity of the sodium bicarbonate+ulinastatin group was significantly higher than the conventional treatment group from the 5th day, and the difference was statistically significant (P<0.05) . The total atropine dosage, total pralidoxime methylchloride dosage and hospitalization days were better than the conventional treatment group, and the differences were statistically significant (P<0.05) . The difference in the time of atropinization between the two groups was not statistically significant (P>0.05) . The results of arterial blood pH, HCO3- of the sodium bicarbonate + ulinastatin group were higher than the conventional treatment group, and the difference of HCO3- at the 10th day was statistically significant (P<0.05) .

CONCLUSIONSSodium bicarbonate combined with ulinastatin can improve the therapeutic effect and reduce complications in the treatment of acute phoxim pesticide poisoning, and have beneficial effects on the recovery of cholinesterase activity.

Atropine ; therapeutic use ; Cholinesterases ; metabolism ; Glycoproteins ; therapeutic use ; Humans ; Organophosphate Poisoning ; drug therapy ; Organothiophosphorus Compounds ; poisoning ; Pesticides ; poisoning ; Pralidoxime Compounds ; therapeutic use ; Sodium Bicarbonate ; therapeutic use