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

Under the catalysis of a variety of metabolic enzymes in vivo, such as UDP-glucuronyl transferases, cytochrome P450, carboxylesterase, sulfotransferase, butyrylcholinesterase, catechol-O-methyl transferase and 6-morphine dehydrogenase, the drugs perform glucuronidation, hydrolysis, oxidation, sulfonation and other reactions, then translate into active or inactive metabolites, which are excreted through urination, bile or the other pathways at last. Different drugs own their different metabolic pathways. This paper introduces the studies about the metabolism of drugs in human and animal in recent years, such as morphine-like drugs, amphetamine, ketamine, cannabis and cocaine, and reviews the research progress about the sites of metabolism, metabolic enzymes, metabolites and physiological activity of those drugs metabolic in vivo.
Alcohol Oxidoreductases/metabolism* ; Animals ; Carboxylesterase/metabolism* ; Catechol O-Methyltransferase/metabolism* ; Cholinesterases/metabolism* ; Cytochrome P-450 Enzyme System/metabolism* ; Glucuronosyltransferase/metabolism* ; Humans ; Illicit Drugs/metabolism* ; Oxidation-Reduction ; Sulfotransferases/metabolism*

BACKGROUND/AIMS: Gastric peristalsis begins in the orad corpus and propagates to the pylorus. Directionality of peristalsis depends upon orderly generation and propagation of electrical slow waves and a frequency gradient between proximal and distal pacemakers. We sought to understand how chronotropic agonists affect coupling between corpus and antrum. METHODS: Electrophysiological and imaging techniques were used to investigate regulation of gastric slow wave frequency by muscarinic agonists in mice. We also investigated the expression and role of cholinesterases in regulating slow wave frequency and motor patterns in the stomach. RESULTS: Both acetycholinesterase (Ache) and butyrylcholine esterase (Bche) are expressed in gastric muscles and AChE is localized to varicose processes of motor neurons. Inhibition of AChE in the absence of stimulation increased slow wave frequency in corpus and throughout muscle strips containing corpus and antrum. CCh caused depolarization and increased slow wave frequency. Stimulation of cholinergic neurons increased slow wave frequency but did not cause depolarization. Neostigmine (1 muM) increased slow wave frequency, but uncoupling between corpus and antrum was not detected. Motility mapping of contractile activity in gastric muscles showed similar effects of enteric nerve stimulation on the frequency and propagation of slow waves, but neostigmine (> 1 muM) caused aberrant contractile frequency and propagation and ectopic pacemaking. CONCLUSIONS: Our data show that slow wave uncoupling is difficult to assess with electrical recording from a single or double sites and suggest that efficient metabolism of ACh released from motor neurons is an extremely important regulator of slow wave frequency and propagation and gastric motility patterns.
Animals ; Cholinergic Neurons ; Cholinesterases* ; Metabolism ; Mice* ; Motor Neurons ; Muscarinic Agonists ; Muscle, Smooth ; Muscles ; Neostigmine ; Peristalsis ; Pylorus ; Stomach

The purpose of the present study was to investigate the effects of cornel iridoid glycoside (CIG) on the activity of cholinesterases in vitro, and to investigate the mechanism of CIG's treating Alzheimer's disease (AD). The sources of cholinesterases were prepared from human blood cells, rat brain homogenate and human blood plasma, respectively. The biochemical methods were used to detect the activity of acetylcholine esterase (AChE) and butyryl cholinesterase (BuChE) to investigate the influence of CIG on cholinesterases. The results showed that CIG inhibited the activity of AChE of human blood cells and rat brain homogenate, with the 50% inhibition rate (IC50) of 1.6 g . L-1 and 3.3 g . L-1, respectively; and the inhibition of AChE of CIG is reversible. CIG also inhibited the activity of BuChE of human blood plasma, with the IC50 of 2.9 g . L-1. In conclusion, CIG can inhibit the activity of AChE and BuChE in vitro, which may be one of the mechanisms of CIG to treat AD.
Acetylcholinesterase ; metabolism ; Animals ; Brain ; drug effects ; metabolism ; Cholinesterase Inhibitors ; pharmacology ; Cholinesterases ; metabolism ; Humans ; Iridoid Glycosides ; pharmacology ; Plasma ; enzymology ; Rats

OBJECTIVETo explore the effect of hemoperfusion(HP) about the patients of methamidophos poisoning.

METHODSOn the basis of comprehensive treatment,15 cases of severe acute methamidophos poisoning patients were treated with HP, Blood samples were collected at 7 time points, before and 5, 15, 30, 45, 60mins following the beginning and the end of hemoperfusion. Blood samples were used for measuring the concentration of methamidophos and perfusion devices were used for measuring the volume of methamidophos adsorbed by the device after hemoperfusion.

RESULTS15 patients live in 12 cases, 3 cases of death. HP (former) blood Cholinesterase vigor were 662.60 + 632.05, HP (after) blood cholinesterase vigor were 2577.52 + 920.38 IU/L; The difference of blood Cholinesterase vigor between the before and after HP was statistically significant (P < 0.01). The patients' methamidophos concentration of blood when HP treated 45, 60, 120 min were respectively (851 + 672), (680 + 529), (587 + 520) microg /ml, there were significantly lower than that the patients' methamidophos concentration of blood who were before HP (1659 + 1105) microg/ml, a statistically significant difference (P < 0.01).

CONCLUSIONHP can be cut down obviously methamidophos poisoning patients serum concentrations of toxic, the experimental method directly prove the clinical application of carbon HP can really adsorption methamidophos.

Adult ; Cholinesterases ; metabolism ; Female ; Hemoperfusion ; methods ; Humans ; Insecticides ; poisoning ; Male ; Middle Aged ; Organothiophosphorus Compounds ; poisoning ; Treatment Outcome ; Young Adult

OBJECTIVETo investigate the effect of exogenous glial cell line-derived neurotrophic factor (GDNF) infused into the cavitas subarachnoidealis on cornu anterius medullae spinalis motor neurons after sciatic nerve axotomy.

METHODSForty-eight healthy SD rats were divided into 2 groups randomly: GDNF group and NS group. The left sciatic nerve in rats were cut off. And then 0.9% saline (6 microl) and GDNF solution (6 microl) were injected into cavitas subarachnoidealis at L4-L6 in NS group and GDNF group,respectively. The rats were sacrificed on postoperative 1, 2, 4 and 8 weeks respectively. Their specimen of L4-L6 spinal cord were taken at different time and sectioned. The HE staining, Nissl staining and cholinesterase (ChE) staining in motor neurons were used for counting of motor neurons.

RESULTSIn GDNF group the number of motor neurons in cornu anterius medullae spinalis and the ChE activity were higher than that of NS group.

CONCLUSIONThe exogenous GDNF infused into the cavitas subarachnoidealis are supposed to protect the degenerated spinal motor neuron from death after sciatic nerve injury.

Animals ; Axotomy ; Cholinesterases ; metabolism ; Glial Cell Line-Derived Neurotrophic Factor ; pharmacology ; Male ; Motor Neurons ; drug effects ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sciatic Nerve ; cytology ; drug effects ; metabolism ; Spinal Cord ; cytology ; drug effects ; metabolism ; surgery

OBJECTIVETo study the pathological changes of blood glucose, serum lipid, insulin resistance, liver function, liver cell denaturalization of total glucosides of paeony on nonalcoholic fatty liver rats caused by insulin resistance and discuss the acting mechanism.

METHODAdult SD rats were maintained on high-fat-sugar-salt diet for 56 days. In the 57th day, their fasting blood glucose (FBG) and 2-hours blood glucose after oral glucose tolerance test (OGTT-2 hBG) were mensurated, according to which and the weight the rats were divided randomly into nonalcoholic fatty liver model group, metformin group (0.2 g x kg(-1)) and total glucosides of paeony group (high dosage 0.15 g x kg(-1), low dosage 0.05 g x kg(-1)). All the rats were still administered the same diet and given different drugs by intragastric administration for 28 days. In the 29th day, all of them were killed and the blood was sampled to measure the levels of blood glucose [FBG, OGTT-2 hBG, fasting insulin (Fins)] and serum lipid [free fatty acids (FFA), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C)], then the HOMA insulin resistance index (HOMA-IRI, fasting glucosexinsulin) and insulin sensitivity index (ISI) were counted. The activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), cholinesterase (ChE), superoxide dismutase (SOD) and the contents of malondialdehyde (MDA) were measured also. Livers were weighed and collected to be observed the pathological changes.

RESULTCompared with normal group, in nonalcoholic fatty liver model group the levels of Fins and IRI were increased obviously (P < 0.01), ISI were decreased (P < 0.01), FFA, TG, TC, LDL-C were increased (P < 0.01), HDL-C were decreased (P < 0.05); the content of MDA were increased (P < 0.05), the activities of SOD were decreased (P < 0.01); AST, ALT and ChE were increased (P < 0.05, or P < 0.01), the pathological changes of liver fat were severe (P < 0.01). In glucosides of paeony group and metformin group, hyperinsulinaemia and insulin resistence were resisted (P < 0.05, or P < 0.01); the levels of FFA, TG, TC, LDL-C were decreased and HDL-C were increased (P < 0.05, or P < 0.01); the activities of AST, ALT, ChE were decreased (P < 0.05, or P < 0.01) and SOD were increased (P < 0.01). The contents of MDA were decreased (P < 0.05). The levels of FBG and 2 hBG in metformin group were decreased but in total glucosides of paeony group were not decreased obviously.

CONCLUSIONTotal glucosides of paeony may protect liver function and modulate serum lipid for the fatty liver rats caused by insulin resistance, and its action mechanism may be concerned with enhancing insulin sensitivity and antioxidative ability, decreasing serum lipid.

Alanine Transaminase ; metabolism ; Animals ; Aspartate Aminotransferases ; metabolism ; Blood Glucose ; drug effects ; Cholesterol, LDL ; blood ; Cholinesterases ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Enzyme Activation ; drug effects ; Fatty Liver ; drug therapy ; prevention & control ; Female ; Glucose Tolerance Test ; Glucosides ; chemistry ; pharmacology ; therapeutic use ; Insulin Resistance ; Lipids ; blood ; Liver ; drug effects ; metabolism ; pathology ; Male ; Malondialdehyde ; metabolism ; Paeonia ; chemistry ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism

OBJECTIVETo observe the effect of huperzine A on cerebral cholinergic system in elderly patients during recovery from general anesthesia.

METHODSThirty elderly patients undergoing elective surgery under general anesthesia were randomized in a double-blind manner into group I (n=15) to receive huperzine A (0.3 mg/2 ml) and group II (n=15) with normal saline (2 ml) given intravenously. Huperzine A or normal saline was administered 30 min before completion of the operation, and acetylcholine (Ach) concentration in the cerebral spinal fluid (CSF) of the patients was determined using high-performance liquid chromatography with electrochemical detector (HPLC-ECD) and the activity of cholinesterase inhibitors (ChE) evaluated with automatic biochemistry analyzer before general anesthesia induction (T1) and 5 h after operation completion (T2).

RESULTSIn both the groups, Ach concentration in the CSF were lower at T2 than that at T1 (P<0.01), and at T2, CSF Ach concentration was significantly higher in group I than in group II (P<0.01); in group I, the activity of CSF ChE at T2 was lower than that at T1 (P<0.01), and also lower than at T2 in group II (P<0.01).

CONCLUSIONHuperzine A can inhibit cholinesterase to increase Ach, which has a positive effect on cerebral cholinergic system in elderly patients during recovery from general anesthesia.

Acetylcholine ; cerebrospinal fluid ; Aged ; Alkaloids ; Anesthesia Recovery Period ; Anesthesia, General ; Brain ; drug effects ; metabolism ; Cholinesterase Inhibitors ; therapeutic use ; Cholinesterases ; cerebrospinal fluid ; Chromatography, High Pressure Liquid ; Double-Blind Method ; Electrochemistry ; Female ; Humans ; Intraoperative Period ; Male ; Sesquiterpenes ; therapeutic use

A modified electrometric method was described and validated for measurement of plasma and erythrocyte cholinesterase activities in 6~18 months old goats. The enzymatic reaction mixture contained 3 ml distilled water, 3 ml barbital-phosphate buffer (pH 8.1), 0.2 ml plasma or erythrocytes and 0.1 ml acetylthiocholine iodide (7.5%) as a substrate. The mixture was incubated at 37 degrees C for 40 minutes. The pH of the reaction mixture was determined by a pH meter before and after the incubation. The initial pH was measured before the substrate addition. The enzyme activity was expressed as deltapH/40 min. The coefficients of variation of the described method in measuring plasma and erythrocyte cholinesterase activities were 4 and 2%, respectively. Preliminary reference values (n = 14) of the mean cholinesterase activity (deltapH/40 min) and 95% confidence interval in the plasma were 0.194 and 0.184~ 0.204, respectively, and those of the erythrocytes were 0.416 and 0.396~0.436, respectively. The pseudocholinesterase activity of the plasma cholinesterase was 63.5% as determined by quinidine sulfate inhibition. The organophosphorus insecticides dichlorvos and diazinon at 0.5~4 micrometer and the carbamate insecticide carbaryl at 5~20 micrometer in the reaction mixture significantly inhibited plasma (13.7~85.5%) and erythrocyte (16.4~71.9%) cholinesterases in vitro in a concentration-dependent manner. The results suggest that the described electrometric method is simple, precise and efficient in measuring blood cholinesterase activity in goats.
Acid-Base Equilibrium/physiology ; Animals ; Carbaryl/pharmacology ; Cholinesterase Inhibitors/pharmacology ; Cholinesterases/*blood/drug effects ; Diazinon/pharmacology ; Dichlorvos/pharmacology ; Enzyme Activation/drug effects/physiology ; Erythrocytes/metabolism ; Goats/*blood ; Plasma/metabolism