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Biomedical subjects

Y J Kao

Publications and source records attributed to Y J Kao.

16 recordsLinked to original sources
PubMed1990

Dose-dependent effect of metoclopramide on cholinesterases and suxamethonium metabolism.

In obstetric patients undergoing postpartum tubal ligation, we found that metoclopramide produced dose-dependent prolongation of suxamethonium-induced neuromuscular block. Mean block times after suxamethonium 1 mg kg-1 were 8.0 min, 9.83 min and 12.45 min for control and metoclopramide 10 mg and metoclopramide 20 mg groups, respectively. A laboratory study was therefore conducted on the inhibition of human plasma cholinesterase (PCHE) and erythrocyte acetylcholinesterase (ACHE) activity by varying concentrations of metoclopramide using acetylthiocholine as substrate. PCHE showed a greater sensitivity to inhibition by metoclopramide; the concentration of metoclopramide producing 50% inhibition of activity (I50) was 3.16 x 10(-7) mol litre-1, which is within the therapeutic range. ACHE was less sensitive to inhibition by metoclopramide (I50 2.24 x 10(-5) mol litre-1). Analysis of enzyme kinetics at varying substrate concentrations revealed that metoclopramide produced a potent non-competitive, dose-dependent inhibition of both ACHE and PCHE. The inhibition constant, Ki, was 1.88 x 10(-7) mol litre-1 for PCHE and 9.5 x 10(-8) mol litre-1 for ACHE. As metoclopramide is a potent inhibitor of PCHE, interactions might be expected to occur between metoclopramide and drugs that require PCHE for biotransformation, such as suxamethonium and ester local anaesthetics.

Cholinesterase Inhibitors↗
PubMed1990

Loss of consciousness after emergence from anaesthesia. A case of suspected micturition syncope.

A case of postanaesthesia micturition syncope with respiratory arrest is described. If syncope occurs, the temporary myocardial ischaemia and cerebral hypoperfusion may increase anaesthetic risk in the marginally compensated patient. The loss of airway protection during the syncopal period is also a cause of concern. We recommend the use of an indwelling bladder catheter during any prolonged surgical procedure.

Anesthesia Recovery Period↗
PubMed1989

Neuromuscular block by suxamethonium following treatment with histamine type 2 antagonists or metoclopramide.

We have examined the effect of preoperative i.v. administration of three different histamine type 2 (H2) antagonists (cimetidine 400 mg, ranitidine 80 mg and famotidine 20 mg) or metoclopramide 10 mg i.v. on the duration of neuromuscular block produced by an intubating dose (1 mg kg-1) of suxamethonium. The study was conducted blindly in 70 post partum patients, weighing between 45 and 120 kg, scheduled for tubal ligation. The duration of neuromuscular block following suxamethonium was measured from a chart recording of train-of-four (TOF) electromyographic responses. The time from onset of 95% block to 25% recovery ("block time") was not significantly different between the groups receiving cimetidine (A), ranitidine (B), famotidine (C), and control (E). However, there was prolongation of neuromuscular block in patients receiving suxamethonium and metoclopramide (D).

Clinical Trials as Topic↗
PubMed1989

Prolongation of succinylcholine block by metoclopramide.

Laboratory and clinical evidence of the inhibition of plasma cholinesterase by metoclopramide was demonstrated. When succinylcholine is used as the substrate and the product choline assayed by choline oxidase-peroxidase-quinone dye colorimetry, the rate of the choline production as optical density change was reduced to 50% by 19.5 X 10(-6) M metoclopramide at 20 degrees C. Prolongation of neuromuscular blockade produced by concurrent administration of succinylcholine and metoclopramide was studied in 22 patients aged between 18 and 40 years undergoing elective gynecological surgery. EMG activity in the adductor pollicis muscle was recorded in response to a train-of-four (TOF) stimulus delivered every 10 s. Patients were randomly divided into two groups: A and B. In both groups, anesthesia was induced with thiopental and maintained with sufentanil and nitrous oxide. Tracheal intubation followed intravenous succinylcholine. Intraoperatively, after returning of neuromuscular function, patients in both groups received 20 mg succinylcholine for the determination of duration of neuromuscular blockade. Time from 95% suppression of baseline twitch following a 20 mg increment of succinylcholine until recovery to 25% of control activity was determined. Thereafter, in group A, patients receive metoclopramide (10 mg iv) followed by succinylcholine 20 mg iv, and patients in group B received succinylcholine 20 mg iv alone. Recovery times were again measured and found to be prolonged in patients receiving metoclopramide compared with those not receiving metoclopramide (P less than 0.05). Metoclopramide has no intrinsic neuromuscular blocking activity, but its ability to inhibit plasma cholinesterase probably is the mechanism by which it prolongs succinylcholine block. Reducing the dose of succinylcholine may be appropriate when metoclopramide is given concurrently.

Adult↗
PubMed1986

Transfer of cholesterol and a fluorescent cholesterol analog, 3'-pyrenylmethyl-23,24-dinor-5-cholen-22-oate-3 beta-ol, between human plasma high density lipoproteins.

A fluorescent cholesterol analog, 3'-pyrenylmethyl-23,24-dinor-5-cholen-22-oate-3 beta-ol (PMCA), has been synthesized as a spectroscopic probe of cholesterol function. The substrate activity of PMCA, about two-thirds that of cholesterol, with lecithin:cholesterol acyltransferase indicates that PMCA is a reasonable cholesterol analog and that the orientation of the substituted sterol in the phospholipid interface is similar to that of cholesterol. The fluorescence properties of PMCA are similar to those of other pyrene-containing compounds that exhibit concentration-dependent excimer fluorescence. The rate of transfer of [3H]PMCA between HDL is about six times faster than cholesterol. These results indicate that the analog will be useful in studies of cholesterol function.

Cholesterol↗
PubMed1979

Reconstituted low density lipoprotein: a vehicle for the delivery of hydrophobic fluorescent probes to cells.

Previous studies have shown that the cholesteryl ester core of plasma low density lipoprotein (LDL) can be extracted with heptane and replaced with a variety of hydrophobic molecules. In the present report we use this reconstitution technique to incorporate two fluorescent probes, 3-pyrenemethyl-23, 24-dinor-5-cholen-22-oate-3 beta-yl oleate (PMCA oleate) and dioleyl fluorescein, into heptane-extracted LDL. Both fluorescent lipoprotein preparations were shown to be useful probes for visualizing the receptor-mediated endocytosis of LDL in cultured human fibroblasts. When normal fibroblasts were incubated at 37 degrees C with either of the fluorescent LDL preparations, fluorescent granules accumulated in the perinuclear region of the cell. In contrast, fibroblasts from patients with the homozygous form of familial hypercholesterolemia (FH) that lack functional LDL receptors did not accumulate visible fluorescent granules when incubated with the fluorescent reconstituted LDL. A fluorescence-activated cell sorter was used to quantify the fluorescence intensity of individual cells that had been incubated with LDL reconstituted with dioleyl fluorescein. With this technique a population of normal fibroblasts could be distinguished from a population of FH fibroblasts. The current studies demonstrate the feasibility of using fluorescent reconstituted LDL in conjunction with the cell sorter to isolate mutant cells lacking functional LDL receptors.

Cells, Cultured↗
PubMed1978

Human kidney alanine aminopeptidase: physical and kinetic properties of a sialic acid containing glycoprotein.

Human kidney alanine aminopeptidase has been purified to apparent homogeneity as judged by electrophoresis and sedimentation in the analytical ultracentrifuge. Amino acid analyses indicate that the enzyme is high in tryptophan content and low in cysteine content. The enzyme contains sialic acid, hexoses, and glucosamine, which make up 21% of its dry weight. In dilute buffer, the enzyme exhibits a molecular weight near 236 000, but in denaturing solvents the enzyme exhibits a molecular weight near 119 500. Zinc analyses by atomic absorption demonstrate 1 mol of zinc for 113 500 +/- 6900 g of protein. The zinc is firmly bound, since exhaustive dialysis against chelating agents does not remove the zinc or inactivate the enzyme. The enzyme is stimulated by Co2+ 1.65-fold, but, in contrast to the enzyme-zinc complex, the enzyme-cobalt complex dissociates upon dialysis. Kinetic studies with a series of aminoacyl-beta-napthylamides indicated that the highest kcat value was obtained for L-alanyl-beta-naphthylamide (8.43 X 10(3)s-1), whereas the lowest Km value was obtained for L-methionyl-beta-naphthylamide (1.4 X 10(-5) M).

Alanine↗