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Biomedical subjects

W G Anderson

Publications and source records attributed to W G Anderson.

34 records · Page 2Linked to original sources
PubMed1981

N-Aralkyl substitution of 2-amino-5,6- and -6,7-dihydroxy-1,2,3,4-tetrahydronaphthalenes. 1. Cardiac and pressor/depressor activities.

Amino substitution o rigid forms of dopamine [2-amino-5,6-dihydroxy-1,2,3,4-tetrahydronaphthalene (A-5,6-DTN) and 2-amino-6,7-dihydroxy-1,2,3,4-tetrahydronaphthalene (A-6,7-DTN)] with aralkyl functionalities was carried out to investigate the role of such structural modifications upon cardiac inotropic/chronotropic and blood pressure activity. Derivatives of A-5,6-DTN were strong vasodepressor agents devoid action was associated with the dihydroxyphenyl-1-methylethyl derivative, which was also an inotropic selective compound. The amino substituent of dobutamine was ineffective in reducing peripheral vascular action when combined with the rigid forms of dopamine. It was also ineffective in imparting inotropic selectivity when combined with A-5,6-DTN. An analysis of these observations in light of existing structure-activity relationships of aminoaralkyl substitution of other catecholamine structure is presented.

Animals↗
PubMed1981

Reproducibility of leucocyte migration from agarose microdroplets.

The 18-hour migration of leucocytes from 31 healthy persons was measured in 33 experiments by the agarose microdroplet method using 15-26 replicate droplets in separate culture wells in each experiment. A comparison of the measurement of the migration of leucocytes by a formula derived from two diameters of the droplets and by planimetry of the projected image of droplets, demonstrated the same wide range of coefficients of variation for the two methods and therefore no important difference in their accuracy. In using a ratio, the migration index, to express the size of differences between experimental groups of cultures, the correct choice of cut-off value demands knowledge of the distribution of that ratio amongst cultures no inhibited by the inclusion of "antigen" or other agent. This could not be ascertained from the observed data because of the practical limitation on the number of samples obtainable in each test. A computer simulation of the sampling process was used to determine this distribution and to evaluate statistical cut-off points. The size of the sample required for conventional degrees of accuracy is shown to vary according to the size of the mean migration area and its standard deviation in unstimulated control cultures. In the study 25/33 (76%) experiments would have been adequately assessed if 30 replicates had been used in every case; if 5 replicates had been used only 2/33 (6%) experiments would have been controlled. In the literature upon leucocyte migration, only 3 or 4 replicates of the control and test cultures are generally described and a cut-off migration index of 0.8 is usually accepted arbitrarily. Our observations indicate that this is an inefficient way of assessing data in such a variable system.

Adolescent↗
PubMed1981

Variability of in vitro migration of human leucocytes.

A comparison of the capillary method (CM) and the agarose microdroplet method (AMM), using the same materials, for measurement of human leucocyte migration in vitro yielded similar large degrees of variability. Between fifteen and twenty-six replicate cultures were established for each method in fourteen subjects The range of the coefficients of variation were .7-28.8% (CM) and 7.2-19.3% AMM). Most of 115 publications reviewed describe only three or four replicates. Their results relating to host responses in the fields of cancer, tissue transplantation and several chronic diseases should be interpreted with regard to the variability of the system. The use of human leucocyte migration in vitro for any purpose should incorporate more stringent statistical control of sample size than has been customary. The use of two standard statistical formulae is proposed as this control.

Cell Migration Inhibition↗
PubMed1979

Conformational analogues of dopamine. Synthesis and pharmacological activity of (E)- and (Z)-2-(3,4-dihydroxyphenyl)cyclopropylamine hydrochlorides.

(E)- and (Z)-(+/-)-2-(3,4-dihydroxyphenyl)cyclopropylamine hydrochlorides were synthesized as part of a program to assess the importance of conformational isomerism with respect to the various peripheral biological actions of dopamine. Although neither of the compounds possessed dopaminergic activity in the canine renal blood-flow model, both agents were weak alpha-adrenergic agonists and exhibited cardiostimulatory properties similar to dopamine. The E isomer was apprxoximately 5 times more potent than the Z isomer in its alpha-adrenergic activity and approximately 15 times as potent in its cardiac effects. Possible reasons for the lack of renal dopaminergic activity exhibited by the E isomer are presented.

Adrenergic alpha-Agonists↗
PubMed1976

Ozone exposure modifies prostaglandin biosynthesis in perfused rat lungs.

Exposure of perfused rat lungs to 3.0 ppm of ozone produced a rapid onset of edema and an increased resistance to inflation. Both the Km and Vmax of the enzymic conversion of arachidonic acid to prostaglandins were decreased by ozone exposure suggesting an uncompetitive inhibition of prostaglandin synthetase by O3. Reduced glutathione failed to prevent the inhibition of prostaglandin synthesis by O3.

Air↗
PubMed1975

Kinetic measurements of the release of prostaglandins from perfused rat lungs.

Prostaglandins released from isolated ventilated and perfused rat lungs were measured by a simple modification of the Vane technique using the rat stomach fundus as a continuous bioassay tissue. Exogenously supplied arachidonic acid was converted mainly to PGF2alpha which was determined by bioassay. A novel method for mixing a stream of inhibitors with the perfusate was used to determine PGF2alpha in the presence of substrate amounts of arachidonic acid. Using this system the apparent Km for PGF2alpha production with arachidonic acid as the substrate was found to be 1.90 X 10(-4)M, while the Ki for aspirin was found to 2.47 X 10(-4)M. These kinetic parameters are close to those reported for cell free systems and subcellular fractions suggesting that both substrate and inhibitor have ready access to the site of prostaglandin synthesis. The method appears to be generally useful to determine the effect of drugs and environment factors on the release of prostaglandins by the lung.

Animals↗
PubMed1975

Antagonism of the uterotonic action of oxytocin in vitro.

Cumulative concentration-effect curves of oxytocin alone and with various antagonists were obtained in vitro on uteri from estrogen-treated rats. Graded concentrations of salbutamol, isoproterenol, papaverine, theophylline, thioglycollate, and MgCl2 produced a decrease in the maximal effect of oxytocin and a shift of the concentration-effect curves to the right. Salbutamol and isoproterenol appeared to act as functional antagonists of oxytocin in which agonist and antagonist each interacted with its own specific receptor to produce a decreased combined effect on a common effector. Antagonism by papaverine or theophylline was increased by prior or simultaneous treatment with salbutamol, isoproterenol, epinephrine, or norepinephrine. The potentiation had a rapid onset, was partially blocked by propranolol, persisted for at least 85 minutes following washout of salbutamol, and was not due to a residual effect of salbutamol. This interaction could result from phosphodiesterase inhibition by papaverine and the accumulation of higher levels of cyclic 3',5'-adenosine monophosphate brought about by adenyl cyclase activation with the sympathomimetic amines.

Albuterol↗
PubMed1975

Interaction between halothane and propranolol on oxytocin-induced uterine contractions.

Halothane and other volatile anesthetics were found to relax uteri maximally contracted by oxytocin and to enhance the relaxant effect of propranolol and other agents (tetracaine, quinidine and chlorpromazine) with local anesthetic properties. Concentration-effect curves for inhibition by propranolol or tetracaine were shifted to the left by halothane. Methoxyflurane, chloroform and diethyl ether also increased the effect of propranolol. The tissue/medium ratio for propranolol was increased by halothane. The uptake of propranolol was saturable and was decreased at 2.5 degrees C, suggesting an active transport mechanism. The increased uptake of propranolol in the presence of halothane was probably insufficient to account for the synergism noted. Inhibition by propranolol and tetracaine was inversely related to the concentration of calcium in the medium. The inhibitory effect of propranolol, tetracaine, quinidine and chlorpromazine appeared to be related to their ability to inhibit calcium transport.

Anesthetics↗
PubMedDate not supplied

Beta-blocking potency of mepindolol and pindolol against isoproterenol-induced inotropic and chronotropic responses in guinea pig atria.

The beta-blocking potencies of mepindolol and pindolol were determined in guinea pig right atria (heart rate) and paced left atria (contractile force) in vitro. Neither agent showed selectivity for blocking rate responses induced by isoproterenol. The pA2 (95% confidence interval) values determined for mepindolol against rate and force responses induced by isoproterenol were 9.96 (9.91-10.01) and 9.52 (9.44-9.60), respectively, and for pindolol, 9.20 (9.15-9.25) and 8.85 (8.76-8.94). Mepindolol was approximately 6.5 times as potent as pindolol. The present evidence does not support the hypothesis of subpopulations of beta-receptors subserving inotropic and chronotropic responses.

Adrenergic beta-Antagonists↗