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Biomedical subjects

D M Turner

Publications and source records attributed to D M Turner.

16 recordsLinked to original sources

Atherogenesis in the White Carneau pigeon. Further studies of the role of carbon monoxide and dietary cholesterol.

Two experiments are described. In the first, 3 pairs of groups of 20 female White Carneau pigeons were fed on diets containing 0.5%, 1% or 2% cholesterol. Birds in one group from each pair were exposed to 150 ppm carbon monoxide (CO) for 6 h on 5 days of each week for 52 weeks, sufficient to raise their carboxyhaemoglobin (COHb) levels to approximately 10%, while those in the other group were sham-exposed under similar conditions. In the second experiment, 3 groups of 40 female pigeons were each fed on a diet containing 1% cholesterol, one group being exposed to CO to give COHb levels of 20%, one to give COHb levels of 10% and one being sham exposed. In addition, 20 birds in the second experiment were fed on the 1% cholesterol diet but were neither exposed to CO nor sham-exposed. Cholesterol enriched diets caused mean plasma cholesterol values in each group to rise sharply within 4 weeks of starting them, but the levels reached were as high with diets containing 0.5% cholesterol as for diets containing 1% or 2% added cholesterol. Exposure to CO increased plasma and aortic cholesterol levels, though this increase was only statistically significant for aortic levels in the second experiment. In both experiments combined exposure to the 1% cholesterol diet and CO resulted in a significant decrease in aortic triglyceride content. The incidence and severity of coronary artery atherosclerosis was associated with increasing dietary cholesterol. It was also associated with exposure to CO in birds given 0.5% or 1%, but not 2%, dietary cholesterol; the increase in birds given 1% was related to the dose of CO. Possible mechanisms are discussed for this effect of CO, which is not found in normally fed birds.

Animals

Lung function in sisal ropemakers.

Lung function was measured by spirometry in 66 workers in a sisal ropemaking factory, and in their matched controls. The major atmospheric contaminant was the lubricant (or a component part thereof) used to soften the fibre. The concentration of airborne matter was generally less than 1 mug m--3. There was no difference in lung function between the two groups before the start of the working shift, that is, the mixture of softening lubricant and sisal caused no long-term effects. Although there was no change in lung function over the working shift in the group making sisal rope, the control group did show a significant increase in lung function over the same period. This suggests that an effect attributable to the lubricant and sisal dust did exist. In previous studies little mention has been made of the softeners used in the processing of sisal fibre. These additives may exert a significant effect on ventilatory capacity and may act in conjunction with sisal dust.

Adult

Smoking habits of blacks in industry.

A number of Black workers from a factory near Johannesburg were questioned about their smoking habits. Compared with an earlier study, a significantly greater number of younger workers now smoke-and mainly cigarettes. The roles played by the strong tobacco lobby and that of the Department of Health are considered.

Adolescent

Sick leave--honour or expediency?

Experience has shown that doctors tend to be overgenerous when awarding sick leave. Quite rightly their first consideration is their patient, but frequently too little thought is given to the overall effect that excessive absence because of illness may have have on the patient, on the company in which he works, and on the country as a whole. Economically, these effects may be profound. A tempered industrial viewpoint is put forward and South African law regarding sick leave is outlined. A plea is made to doctors to safeguard their sick leave notes, prescription pads or letterhead paper, to award sick leave on merit, giving legible sick leave notes containing the necessary information, and to the profession not to overlook the wider aspects of the matter.

Absenteeism

The effects of some tobacco smoke constituents on foreign compound metabolism in the cat and the rat.

The effects of chronic nicotine administration on its own metabolism have been studied in the cat and the rat. Nicotine administration caused an increase in the in vitro metabolism in the liver of both species and in cat kidney. Cotinine production from nicotine was enhanced in both species by pretreatment with nicotine. The magnitude of the increase in enzyme activity was relatively small but of the same order as that produced, in the rat, by phenobarbital treatment. 3-methylcholanthrene pretreatment stimulated rat liver nicotine metabolism but was without effect on cotinine production. Chronic exposure of rats to relatively low levels of carbon monoxide inhibited the in vitro aryl hydrocarbon hydroxylase activity but did not affect nicotine metabolism. The data are discussed in relation to the observed enzyme inductive effects of tobacco smoke.

Animals

The effect of intermittent carbon monoxide exposure on experimental atherosclerosis in the rabbit.

(1) Twenty-four female New Zealand White rabbits were fed commercial diet plus 2% cholesterol. Twelve of these animals were exposed to carbon monoxide for 4 hours per day, seven days per week for 10 weeks. The carbon monoxide exposure was such that the mean blood carboxy-haemoglobin was raised to approximately 20% during each exposure period. Twelve control animals breathed atmospheric air under the same conditions of confinement as the carbon monoxide-exposed group. (2) No significant differences in the plasma levels of cholesterol, triglycerides or glutamate oxalacetate transaminase were observed between the two groups during the experiment. (3) When the animals were sacrificed at the end of the experiment no significant differences were observed between the two groups in the aortic content of triglycerides, cholesterol or phospholipids. (4) The extent of coronary artery atherosclerosis was statistically significantly higher in the carbon monoxide group than in the control group. (5) Ultracentrifugal analysis of plasma lipoproteins revealed that there was significantly more cholesterol in the d less than l.006 fraction from the CO-exposed rabbits. (6) These findings, are discussed with particular reference to the claim that the causal agent in tobacco smoke associated arterial disease is carbon monoxide.

Animals

Absorption and metabolism of nicotine from cigarettes.

Eight men volunteers each smoked a single cirgarette containing 14C-nicotine and gave arterial blood samples during and for 50 minutes after smoking. The maximum concentration of nicotine in the arterial blood ranged from 31 to 41 mug/l in four regular cigarette smokers who inhaled. Two non-smokers achieved maximum levels of 2 and 4 mug/l. On a separate occasion two of the inhalers received 1 mg. 14C-nicotine in 10 divided doses injected intravenously. In both cases the peak arterial nicotine concentrations bore a similar relationship to the intravenous dose, as did the peak nicotine concentrations to the retained doses during smoking.

Absorption

Plasma triglyceride secretion in squirrel monkeys: effects of nicotine.

The acute effects of intravenous nicotine on the appearance of plasma triglycerides have been studied in anaesthetised squirrel monkeys given Triton-WR 1339. At both dose levels studied, 4 and 10 mug/kg/30 sec, nicotine caused a stimulation in the rate of accumulation of plasma glycerides, the larger dose producing the greater effect. Nicotine caused a transient elevation in plasma free fatty acids (FFA), also in proportion to the dose given. It is suggested the changes in plasma glycerides are due to enhanced hepatic secretion secondary to increased plasma FFA. The administration of Triton-WR 1339 caused a rapid and sustained fall in plasma cholesterol concentrations. This fall was similar to that observed in plasma Triton and evidence is presented to suggest that Triton and cholesterol are removed from the circulation by a similar mechanism. There was no effect of nicotine on plasma cholesterol. The implications of the effects of nicotine of plasma triglycerides in relation to coronary heart disease are discussed briefly.

Animals

Metabolism of nicotine by the isolated perfused dog lung.

1. Metabolism of [14C]nicotine has been studied in the isolated perfused dog lung. [14C]Nicotine, 50 mug every 30 s for 10 min administered via the pulmonary artery, undergoes first pass metabolism to a small extent. [14C]Cotinine was detected in the venous blood. Of the injected activity, 6 percent was in the lung at the end of experiment; 60 percent being present as [14C]nicotine and 20 percent as [14C]nicotine-1'-oxide. 2. When [14C]nicotine was administered in cigarette smoke a greater degree of metabolism was observed at first pass. Pyrolysis products of [14C]nicotine also were present in the venous blood. Lungs after smoke exposure contained 30 percent of administered radioactivity, with a substantial proportion of [14C]nicotine-1'-oxide. 3. Administration of [14C]nicotine-labelled smoke to lung preparations, on closed circuit, gave significant amounts of [14C]cotinine and other metabolites over a 2 h period. Lung tissue contained approx. 40 percent of injected dose, of which 25 percent only was [14C]nicotine. Large proportions of [14C]cotinine and [14C]nicotine-1'-oxide were present but 45 percent of the activity was present as other unidentified pyrolysis products. [14C]Demethyl cotinine was detected.

Animals

Influence of route of administration on metabolism of [14C]nicotine in four species.

1. The metabolism of [14C]nicotine has been studied in four species of animals, rabbit, rat, cat and squirrel monkey, after administration by different routes. 2. Intravenous injection of 4 mug/kg [14C]nicotine every 60 s for 1 h results in peak blood levels of approximately 100 ng/ml in all species but the rabbit. [14C]Cotinine levels in blood vary widely between species. 3. Subcutaneous injection of 0.4 mg/kg [14C]nicotine produces similar peak blood nicotine levels but the time course, for a given species, is different. 4. Intragastric instillation of 1 mg/kg [14C]nicotine to the cat and rabbit results in much lower levels of [14C]nicotine in blood and relatively high levels of [14C]cotinine. 5. Urinary excretion data indicate that, irrespective of route, the squirrel monkey excretes only a small proportion of the dose into urine during the period of experiment, of which the major proportion is [14C]nicotine. The cat, in contrast, excretes a relatively large proportion of the dose during the experimental period though only a minor proportion of the radioactivity is due to [14C]nicotine or [14C]cotinine. 6. All four species are potentially useful for model experiments with nicotine, though metabolism of nicotine by squirrel monkey is most similar to man.

Administration, Oral

The effect of tobacco smoke and some of its constitutents on triglyceride secretion in the squirrel monkey.

The acute effects of tobacco smoke and some of its constituents on plasma free fatty acid levels and on triglyceride secretion were studied in anaesthetized squirrel monkeys given Triton WR-1339. All the treatments raised plasma free fatty acids in the order high tar smoke greater than medium tar vapour phase = air:CO greater than medium tar smoke. Plasma triglyceride secretion in animals inhaling high tar smoke did not differ from controls. There was a transient rise in triglyceride secretion in animals inhaling vapour phase but the largest increase (after a significant delay) was in monkeys breathing air:CO. Maximal concentrations of blood carboxyhaemoglobin did not differ between the experimental groups. It is suggested that, under these experimental conditions, there are present in the particulate phase of tobacco smoke factors which inhibit hepatic triglyceride secretion.

Animals