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Biomedical subjects

W D Paton

Publications and source records attributed to W D Paton.

At least 37 records · Page 2Linked to original sources
PubMed1979

The effects of some hydrophobic gases on the pulmonary surfactant system.

1. Decompression from exposures to raised ambient pressure of sulphur hexafluoride, carbon tetrafluoride, hexafluoro-ethane and nitrous oxide results in the formation of dense foam and pulmonary oedema. 2. The degree of pulmonary oedema produced is dependent on the exposure pressure, although the exposure time required is short in comparison to tissue saturation times. 3. The effect is not prevented by atropine, ephedrine or hydrocortisone. 4. The effect is also produced in vitro by saturated solutions of halothane, chloroform and ether. 5. It is suggested that the mechanism of action is physical with physico-chemical factor involved being a differential partition of these gases within the surfactant: membrane complex.

Animals↗
PubMed1979

The effects of high pressure helium and nitrogen on the release of acetylcholine from the guinea-pig ileum.

1 The effects of high pressures of helium and of nitrogen on acetylcholine release were tested using the guinea-pig ileum as a model preparation. A superfusion system was designed in which this tissue could be maintained under physiological conditions in a high pressure chamber.2 Helium, at a pressure of 136 atm slightly increased the spontaneous output of acetylcholine but produced no significant changes at 68 atm (136 atm is close to the lethal pressure for small mammals).3 The acetylcholine release evoked by electrical stimulation or by 55 mM potassium was not altered by 136 atm of helium. Effects on tetrodotoxin-treated tissues were not consistent.4 Nitrogen, which in contrast to helium possesses general anaesthetic properties, caused considerable increases in spontaneous and in electrically evoked acetylcholine output at pressures which produce anaesthesia. These increases were not changed when helium was used to increase the total pressure to 136 atm, although this reverses the general anaesthetic actions of nitrogen in vivo.5 The increases in rate of acetylcholine release produced by nitrogen were observed in tetrodotoxintreated tissues and in tissues from reserpine-treated animals. In a calcium-free medium the increases were considerably smaller.6 The conclusions from these results are that while high pressures of helium caused little or no change in acetylcholine release rates, nitrogen produced large changes, which were not due to effects on axonal conduction. The effect of nitrogen is not apparently related to its general anaesthetic actions. Differences such as these in transmitter release would be likely to contribute to the differing physiological effects of these two gases.

Acetylcholine↗
PubMed1979

The effects of inert gases and other general anaesthetics on the release of acetylcholine from the guinea-pig ileum.

1 The actions of a range of general anaesthetic agents on the rates of release of acetylcholine from the guinea-pig ileum were tested, by means of a superfusion system designed to maintain the tissues under physiological conditions in a high pressure chamber.2 Anaesthetic pressures of nitrous oxide, nitrogen, argon, sulphur hexafluoride and carbon tetrafluoride caused increases in acetylcholine ouput but the concentrations required did not parallel their general anaesthetic potencies. The changes were not altered by the application of a pressure of helium which reverses their general anaesthetic actions in vivo.3 Urethane (50.5 mM and 101 mM, but not 16.8 mM) decreased acetylcholine release rates and this effect was not reversed by helium pressure.4 Octanol (1.0 mM, but not 0.124 mM or 0.496 mM) decreased the acetylcholine output. This action was not reversed by helium pressure. The lack of effect on acetylcholine release from tetrodotoxin-treated tissues suggested that the changes were produced by blockade of action potential conduction.5 Phenobarbitone (0.4 mM but not 0.2 mM) also decreased acetylcholine output. Although the concentrations required were lower than those which have been previously shown to block axonal conduction, no changes were seen in tetrodotoxin-treated tissues. The decreases were less when helium pressure was applied than at atmospheric pressure but full pressure reversal, as occurs in vivo, was not seen.6 The effects on acetylcholine output exerted by the anaesthetics studied did not reflect their general anaesthetic action in the concentrations required, the direction of the changes produced or in the response to helium pressure. They represent specific actions which are likely to contribute to the individual differences which are seen between the physiological actions of the anaesthetics in vivo.

Acetylcholine↗
PubMed1979

Ultrasonic imaging system for the study of decompression-induced gas bubbles.

An high-resolution pulse echo ultrasonic imaging system has been developed to study decompression-induced gas bubbles. It was considered necessary that the system be capable of detecting gas bubbles with a diameter of 10 micrometer and up and be able to monitor the growth of these bubbles. In addition the system needed to be capable of distinguishing separate gas bubbles from within an area containing a number of bubbles and allowing their position to be accurately located. The current system is capable of detecting bubbles as small as 10 micrometer and of resolving bubbles separated by 0.8 mm in azimuth and 0.4 mm in range, and these values correspond to the maximum accuracy of location. Finally, it has been shown that the technique is extremely unlikely to induce any bubble formation by means of cavitation or thermal mechanisms. It is concluded that the system represents a powerful method for studying the factors controlling bubble formation.

Decompression↗
PubMed1978

The effects of delta1-tetrahydrocannabinol on mammary gland growth, enzyme activity and plasma prolactin levels in the mouse.

DELTA1-tetrahydrocannabinol (delta1-THC), a highly lipid soluble and active principle of cannabis, was injected each day (25 mg/kg) s.c. in mice from the estimated 13th day of pregnancy. Delta1-THC-treated mice showed no increase in the wet weight or DNA content of their mammary glands during the period of investigation from before parturition until the 12th day post-partum. A marked increase in mammary-gland lipoprotein lipase activity w,s found in control mice at parturition and this was suppressed by delta1-THC. Prolactin rose to a peak level in plasma earlier in lactation in the control mice than in the delta1-THC-treated mice. This delayed rise in plasma prolactin due to delta1-THC may account for the depression of mammary gland growth and development by the drug and for the delay in the appearance of high activities of lipoprotein lipase until later in lactation.

Animals↗
PubMed1978

Potency of mixtures of general anaesthetic agents.

The anaesthetic potencies of binary mixtures of the gases argon (Ar), nitrous oxide (N2O) and sulphur hexafluoride (SF6) have been measured using mice. The mixtures SF6-N2O and N2O-Ar showed additive behaviour, whereas the constituents of the mixture SF6-Ar were non-additive, having a smaller total potency than expected. Further experiments on this mixture with Italian Great Newts and on the carbon tetrafluoride mixtures CF4-Ar and CF4-SF6 with mice suggested that the anomalous potencies may arise from specific pulmonary effects associated with the breathing of SF6 accompanied by a high pressure of some other gas.

Anesthesia, Inhalation↗
PubMed1978

Identification of six substituted 4''-hydroxy-metabolites of of delta1-tetrahydrocannabinol in mouse liver.

4''-Hydroxylation is shown to be a major metabolic route for delta1-tetrahydrocannabinol (delta1-THC) in the mouse. Metabolites were extracted from the livers of mice treated with delta1-THC and examined by combined gas chromatography-mass spectrometry. The 7-hydroxy-6alpha,7-dihydroxy-, 6-oxo- and 7-hydroxy-6-oxo- derivatives of 4''-hydroxy-delta1-THC together with the 4''-hydroxy- and 4'',6alpha-dihydroxy-derivatives of delta1-THC-7-oic acid were identified. Only the diol, 4'',7-dihydroxy-delta1-THC has been reported previously.

Animals↗
PubMed1977

In vivo metabolism of cannabinol by the mouse and rat and a comparison with a metabolism of delta 1-tetrahydrocannabinol and cannabidiol.

The in vivo liver metabolism of cannabinol has been studied in the mouse and rat by combined gas chromatography and mass spectrometry. Cannabinol glucuronide was the major metabolite of cannabinol in the mouse and was accompanied by relatively large amounts of 7-hydroxycannabinol, cannabinol-7-oic acid and their corresponding glucuronide conjugates. Lower concentrations of glucuronides were found in the rat. Two series of disubstituted metabolites were found containing either a 7-hydroxyl or a 7-carboxylic acid group and a second hydroxyl group in the 1 inch-4 inch positions of the sidechain. These were of low concentration in the mouse but higher in the rat; 1 inch-hydroxy metabolites were particularly abundant in the latter species. Also found in the rat livers were small amounts of sidechain monohydroxy metabolites and larger quantities of 4 inches, 5 inches-bisnorcannabinol-3 inches-oic acid; these were absent in the mouse. The metabolites were identified using the trimethylsilyl (TMS), [2H9] TMS and methyl ester-TMS derivatives, and by reduction of acid metabolites with lithium aluminium deuteride to the corresponding alcohols.

Animals↗
PubMed1977

Identification of di- and tri-substituted hydroxy and ketone metabolites of delta1-tetrahydrocannabinol in mouse liver.

In vivo liver metabolites of delta1-tetrahydrocannabinol (delta1-THC) were examined with a gas chromatograph--mass spectrometer--computer system as trimethylsilyl (TMS), [2H9]TMS and methyloxime-TMS derivatives. In addition to the reported monohydroxy, acid, and hydroxyacid metabolites, the following multiply substituted metabolites were identified: 2'',7-, 3'', 7-, and 6beta,7-dihydroxy-delta1-THC; 2'',6alpha,7-, and 3'',6alpha,7-trihydroxy-delta1-THC; 2''-, 3''-, and 7-hydroxy-6-oxo-delta1-THC, and 2'',7- and 3'',7-dihydroxy-6-oxo-delta1-THC. The ketones and hydroxyacids were reduced to common alcohols with lithium aluminium deuteride and the number of deuterium atoms in the product was used to distinguish the metabolic alcohols from those produced by reduction.

Animals↗
PubMed1977

Identification of glucuronides as in vivo liver conjugates of seven cannabinoids and some of their hydroxy and acid metabolites.

Glucuronide conjugates of cannabidiol (CBD), 7-hydroxy-CBD, propyl-CBD, cannabinol (CBN), 7-hydroxy-CBN, CBN-7-oic acid, propyl CBN and cannabichromene have been identified as major metabolites of CBD, CBN and their propyl homologues and of cannabichromene in mouse liver. Trace amounts of the glucuronide conjugates of delta1- and delta1(6)-tetrahydrocannabinol (THC) were also detected. Identification was made by combined gas-liquid chromatographic and mass spectrometric studies of the trimethylsilyl (TMS), d9-TMS and methyl ester-TMS derivatives of the glucuronides and the TMS derivatives of the product of the reduction of the metabolites with lithium aluminium deuteride.

Animals↗
PubMed1976

Pressure antagonism of anaesthetic-induced conduction failure in frog peripheral nerve.

Experiments to investigate pressure-induced antagonism of the effects of general anaesthetics in isolated peripheral nerve from the frog are described. The doses of four gaseous general anaesthetic agents required to reduce electrically evoked action potentials by 50% (mean +/- SEM) were nitrous oxide 490 +/- 40.4 kPa, ethylene 665 +/- 212 kPa, dichlorodifluoromethane 108 +/- 17.2 kPa and cyclopropane 70 +/- 5 kPa. The combination of high pressure and the anaesthetic agent partially or completely restored the action potential amplitudes for the gaseous and some of the volatile agents (chloroform, diethyl ether, helothane). However, reversal of the effects of other volatile agents (ethanol, butanol), sodium pentobarbitone and two local anaesthetic agents (procaine, dibucaine) did not occur. The pressures used to effect a reversal were less than anticipated. This apparent inconsistency with the critical volume hypothesis for anaesthesia is discussed.

Anesthesia, Inhalation↗