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Biomedical subjects

L B Wingard

Publications and source records attributed to L B Wingard.

At least 37 records · Page 2Linked to original sources
PubMed1983

Immobilized adriamycin: a tool for separating cell surface from intracellular mechanisms.

Pharmacologic agents may exert their biological activity at the level of the cell membrane. Of particular interest is the anticancer agent adriamycin. This drug has previously been considered to act by intercalation with nuclear DNA, but recent evidence suggests the possibility that the cell surface membrane may represent an alternative target. To test this hypothesis, adriamycin was attached to insoluble supports, and conditions suggesting that the drug was actively cytotoxic without entering cells were demonstrated.

Animals↗
PubMed1983

Immobilized enzyme electrodes for glucose determination for the artificial pancreas.

Immobilized enzymes are useful in the development of techniques for analytical chemistry measurements, primarily because of the specificity of enzymes for given substrates. In the case of glucose an in vivo assay is needed for closed loop operation of an artificial pancreas insulin delivery system. Several enzymatic methods are available for in vitro determinations of glucose, but only two or three of these methods hold any promise of adaptation for in vivo use. The most promising enzymatic approaches include the use of immobilized glucose oxidase in conjunction with 1) an oxygen electrode to give an amperometric output or 2) a reference electrode to give a potentiometric output. The use of glucose oxidase or other D-glucose-specific enzymes in conjunction with sensitive thermistors to measure the heat of reaction may also be a feasible method. The two most promising approaches are described in terms of their feasibility for continuous measurement of blood glucose levels in vivo without the necessity of withdrawing body fluids for the assay.

Blood Glucose↗
PubMed1980

Pancuronium in caesarean section and its placental transfer.

Pancuronium bromide was used in 49 patients undergoing repeat elective Caesarean section. In 26 patients who received only pancuronium 0.1 mg kg-1, pancuronium was detected in all umbilical venous or arterial samples (0.12 micrograms ml-1). In 23 other patiets who received suxamethonium 1.0 mg kg-1 followed by pancuronium 0.05 mg kg-1, pancuronium was detected in fetal blood 2 min after injection; the concentration of pancuronium in umbilical venous or arterial samples in 14 subjects was 0.08 micrograms ml-1, and less than 0.05 micrograms ml-1 in nine subjects. There was no evidence that such concentrations of pancuronium were detrimental to the fetus. The use of suxamethonium before pancuronium resulted in reduction of pancuronium dosage, induction-delivery time, and fetal concentrations of pancuronium, and was associated with better condition of the neonate.

Adult↗
PubMed1979

Effects of physostigmine, scopolamine, and mecamylamine on the sleeping time induced by ketamine in the rat.

Male Sprague-Dawley rats weighing 116--241 g were injected i.p. with ketamine hydrochloride, 80 mg per kilo of body weight. Immediately after loss of righting reflex, scopolamine, physostigmine, and mecamylamine were administered i.p. to different groups of rats. Control animals received sterile saline by the same route. The ketamine-induced sleeping time was significantly prolonged by physostigmine and scopolamine, but not by mecamylamine. After the delayed injection of physostigmine, the ketamine sleeping time was longer. These results, although too preliminary for a mechanistic interpretation, suggest that multiple neurotransmitter systems, probably including the cholinergic system, are involved in the mechanism of action of ketamine-induced narcosis.

Animals↗
PubMed1979

Immobilized enzyme electrodes for the potentiometric measurement of glucose concentration: immobilization techniques and materials.

Glucose oxidase, catalase, and bovine serum albumin were co-immobilized with glutaraldehyde around a platinum screen or around a single platinum-iridium wire. The potential difference between this dual enzyme electrode and a Ag/AgCL reference electrode was proportional to the logarithm of the glucose concentration over the range from 10 to about 150 mg glucose per 100 ml in buffered solution at pH 7.4 and 37 degrees C. The enzyme electrode responded in serum only if coated with a semipermeable film, such as cellulose acetate, to exclude serum macromolecules. The potentiometric results were similar to those obtained with the two enzymes co-immobilized in polyacrylamide gel around a platinum screen or with only one of the enzymes, glucose oxidase, covalently coupled to a platinum screen. The results so far suggest that glucose for development of a continuous in vivo glucose sensor.

Catalase↗
PubMed1979

Modified fluorometric quantitation of pancuronium bromide and metabolites in human maternal and umbilical serums.

The procedure for pancuronium bromid ion-pair extraction into chloroform using rose bengal and subsequent fluorometric measurement was modified by changing the extraction pH and eliminating phenol, ethanol, and acetone to give easier operation and enhanced fluorescence stability. Precision, accuracy, and sensitivty were evaluated over 0.14-0.82 microgram/ml (CV = 14; relative error = 9%) and 0.05-0.17 microgram/ml (CV = 19; relative error = 21%). Following a dose of 0.1 ml/kg for cesarean section in humans, the mean maternal arterial and umbilical venous serum concentrations of pancuronium bromide and metabolites were 0.52 and 0.12 microgram/ml, respectively, at delivery (mean of 13 min after injection).

Female↗
PubMed1979

Immobilization of neuraminidase and its potential application in the modification of cell surfaces.

Vibrio cholerae neuraminidase was immobilized on the inside of 1.0 mm inner diameter nylon tubing with retention of enzyme activity, when assayed at 37 degrees C and pH 5.5 with mucin as substrate. The stabilities of the immobilized and soluble enzymes were similar for up to 3 hr at 37 degrees C. Preliminary data indicated that immobilized neuraminidase will release sialic acid from the surface of leukemic AKR mouse thymus and spleen lymphocytes; however, the level of immobilized enzyme activity needs to be increased for practical applications. With this improvement immobilized neuraminidase could become a novel preparation for carrying out cell surface modifications with minimal enzyme contamination of the cell.

Animals↗
PubMed1978

Pharmacokinetics of warfarin enantiomers: a search for intrasubject correlations.

The total body clearance of single doses of R(+)-, S(-)-, and racemic warfarin and the plasma concentration-anticoagulant effect curves for these drugs were determined in 10 healthy men, 21 to 51 yr old. This information was used to calculate the steady-state dose required to decrease prothrombin complex activity to about 30% of normal. This dose (mean +/- SD in mg/70 kg/day) is 17.8 +/- 9.3 for R(+)-warfarin, 6.63 +/- 2.19 for S(-)-warfarin, and 9.4 +/- 1.7 for racemic warfarin. There is a correlation between the maintenance doses of racemic and S(-)-warfarin (r = 0.89, p less than 0.01) but not between those of racemic and R(+)-warfarin (r = 0.30, NS). According to these calculations, the maintenance dose of racemic warfarin required by an individual patient may be a useful predictor of maintenance dose of S(-)-warfarin which will produce a comparable degree of anticoagulation. No such predictability is evident with respect to R(+)-warfarin. The slopes of the log plasma concentration-anticoagulant effect curves for R(+)-and S(-)-warfarin differ significantly. Therefore, the potency ratio of these enantiomers is dose-and concentration-dependent.

Adult↗
PubMed1978

Comparative pharmacokinetics of coumarin anticoagulants XXXV: Examination of possible pharmacokinetic interaction between (R)-(+)- and (S)-(--)-warfarin in humans.

The elimination kinetics and anticoagulant effect produced by single 1.5-mg/kg doses of (R)-(+(-, (S)-(--)-, and racemic warfarin were determined in 10 healthy men. The results obtained in experiments with the individual enantiomers were used to predict the elimination kinetics and anticoagulant effect of racemic warfarin, assuming that there is no interaction between the two enantiomers. These predictions were compared to experimental results, and no significant differences were observed. This finding suggests that there are no pronounced pharmacokinetic or pharmacodynamic interactions between single large doses of (R)-(+)- and (S)-(--)-warfarin in humans.

Adult↗
PubMed1978

Kinetics of methotrexate uptake by human tumor cells from routine pathological samples.

The kinetics of cell uptake of methotrexate were measured in vitro using primary human tumor cells from malignant pleural effusions, leukemic cells from leukopheresis samples, and normal tonsillar lymphocytes. The results were consistent with either passive diffusion or carrier mediated uptake kinetics, with the latter applicable only under conditions where the extracellular concentration of methotrexate was smaller than the drug-transport receptor binding constant. The intial rates of uptake for the same cell type differed signicantly between patients; however no differences in uptake rates were noted between cell types. All three sources of cells proved suitable for uptake studies. The results suggest that the variation in response in normally methotrexate responsive neoplasms, such as leukemia or lymphoma, may be due to between-patient differences in the cellular rates of methotrexate uptake.

Adolescent↗
PubMed1977

Effect of warfarin on the kinetics of the vitamin K-dependent clotting factors in rats.

The objectives of this study were to compare the time course of activities and rates of synthesis of activities for the separate clotting factors II, VII, IX, and X and to relate the rate of synthesis of activity of each factor to the plasma concentration of warfarin in individual rats after acute and chronic dosing with warfarin. Sequences of blood samples were obtained from each rat for 50 to 70 hours after an acute dose of warfarin or for 120 hours after a chronic loading dose plus 12-hour maintenance doses of warfarin and assayed for factor activities and warfarin concentration. The half-lives for degradation of factor activities ranged from 2.6 to 9.0 hours for the four factors. During periods of changing warfarin concentration (acute dosing) factor VII and X activities and rates of synthesis of activity showed large rapid changes, while factors II and IX responded more slowly. As the warfarin concentration diminished, the factor X rate of synthesis of activity appeared to exceed predrug values in all rats. During chronic dosing with warfarin the factor II activity and rate of synthesis of activity was depressed the most. The percent depression of the rate of synthesis of activity for each factor was related linearly to the logarithm of the plasma concentration of warfarin for the range 0 to 80% depression with acute dosing. However, this relationship was not suitable to explain the apparent overshoot in factor X rate of synthesis of activity.

Animals↗
PubMed1976

Pharmacokinetics of succinylcholine in infants, children, and adults.

The elimination of succinylcholine appears to follow first-order kinetics with a linear relationship between intensity of effect and logarithm of the dose. Determination of the time-course of neuromuscular blockade following succinylcholine in infants and children allowed us to compare the rate of recovery and elimination rate constant with those determined by others in adults. The rate of recovery was independent of dose for each age group. The rate of recovery was faster in children than in infants; the rate of recovery of infants was faster than that of adults. The elimination rate constant for infants was similar to that of children; for both the infants and children the rate constants appeared dissimilar from those of adults.

Adult↗
PubMed1976

Pharmacodynamics of tubocurarine in humans.

The pharmacodynamics of neuromuscular transmission, following blockade by a single i.v. dose of tubocurarine (dtc) in humans, were simulated from experimental serum dtc concentration versus time data and serum dtc concentration versus percentage recovery data. Good agreement was obtained between the simulated and experimental time course of recovery at five different therapeutic doses. The initial apparent volume of distribution (Vapp) of dtc was approximately the same as the serum volume and appeared to increase with the size of the dose. These results were consistent with the suggestion that a greater fraction of the dose of dtc was distributed in non-vascular spaces or bound to tissue at larger doses. A pharmacodynamic working model using an average Vapp of 2848 ml simulated times up to 40% recovery within 15-20% error for doses of dtc of 0.30 mg/kg or less.

Dose-Response Relationship, Drug↗
PubMed1975

Effect of bilirubin on the distribution, elimination and anticoagulant action of dicumarol in Gunn rats-1-2 (38547).

Jaundiced Gunn rats were found to have a significantly larger apparent volume of distribution and higher rate constant for elimination of dicumarol than their nonjaundiced littermates. Anticoagulant effect-log plasma dicumarol concentration lines were parallel in the two groups of animals, with the line for the jaundiced rats shifted to a lower concentration range. In vitro studies showed that bilirubin can displace dicumarol from serum protein binding sites. There are indications of a genetic influence on the distribution and anticoagulant effect of dicumarol in Gunn rats.

Animals↗