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Biomedical subjects

G H McIntosh

Publications and source records attributed to G H McIntosh.

At least 37 records · Page 2Linked to original sources
PubMed1990

Effect of a high fat/cholesterol diet with or without eicosapentaenoic acid on plasma lipids, lipoproteins and lipid transfer protein activity in the marmoset.

Marmosets fed a diet supplemented with 0.2% cholesterol and 10% sheep fat (by weight) developed hypercholesterolemia with a 4-fold increase in plasma cholesterol (4.28 +/- 0.57-16.38 +/- 4.22 mmol/l, mean +/- SD, P less than 0.001). This was due mainly to a 5-fold increase in the intermediate density lipoprotein (IDL) and low density lipoprotein (LDL) fraction (d = 1.006-1.063 g/ml). The proportion of plasma cholesterol in high density lipoproteins (HDL) decreased from 56% to 25% although HDL cholesterol increased from 2.40 +/- 0.42 to 4.09 +/- 0.92 mmol/l (P less than 0.001), and HDL particle radius increased from 5.10 +/- 0.18 nm to 6.06 +/- 0.73 nm (P less than 0.05). Plasma lipid transfer protein (LTP) activity increased 2.5-fold in whole plasma and 2-fold in lipoprotein-deficient plasma. The atherogenic lipoprotein profile was attenuated by adding 0.8% eicosapentaenoic acid (EPA, 20:5 n - 3, as the ethyl ester) to the atherogenic diet. Plasma cholesterol increased only 55% to 6.64 +/- 2.55 mmol/l with only an 80% increase in lipoproteins in the d = 1.006-1.063 g/ml fraction and a more favourable proportion of plasma cholesterol in HDL (44%) than without EPA. LTP activity was reduced to 1.7-fold above control in whole plasma by addition of EPA to the atherogenic diet. There was a positive correlation between plasma cholesterol and LTP activity in whole plasma (r = 0.89, P less than 0.001) and in lipoprotein-deficient plasma (r = 0.67, P less than 0.001). EPA therefore attenuated some of the adverse effects of a 0.2% cholesterol, 10% sheep fat diet on plasma lipids and lipoproteins and induced a less atherogenic profile.

Animals↗
PubMed1989

Measurement of aspirin concentrations in portal and systemic blood in pigs: effect on platelet aggregation, thromboxane and prostacyclin production.

Low doses of enteric-coated aspirin were administered orally to pigs. Plasma aspirin concentrations measured in blood obtained simultaneously from permanent catheters in a systemic artery and portal vein for 6 hours after dosage showed a large variation in the plasma aspirin concentration: time profile between pigs. After 50 mg single dose the ratio of the arterial: portal area under the plasma concentration versus time curve (AUC) was 0.63 +/- 0.08 (mean +/- SE, n = 6). In three pigs which received all three dosage regimens, the arterial: portal AUC ratios were 0.48 +/- 0.05 after 50 mg single dose, 0.52 +/- 0.02 after 100 mg single dose and 0.47 +/- 0.02 after 100 mg daily for 1 week. Platelet aggregation in response to sodium arachidonate (1.65 mM) was completely abolished after chronic aspirin administration of 100 mg daily. Thromboxane production (pg/10(6) platelets) induced by this stimulus decreased from 536 +/- 117 before aspirin to 57 +/- 14 after aspirin (mean +/- SE, n = 4; p = 0.03). Aortic prostacyclin synthesis, measured as 6-keto PGF1 alpha (ng/disc after 10 min incubation), was 1.66 +/- 0.28 (mean +/- SE, n = 4) in untreated pigs and 0.95 +/- 0.25 (n = 5) in treated pigs (p = 0.07). Results from this study support the idea that a difference between aspirin concentrations in the portal and systemic circulations can be achieved. Whether this can be translated into a clinically useful differential effect on the vessel wall compared to the platelet remains to be determined.

Animals↗
PubMed1989

Malnutrition in aboriginal children at Yalata, South Australia.

Comparative studies of body weight, height, intracellular water representing cell mass, and age, and plasma concentrations of albumin, vitamins, trace elements and iron stores in Aboriginal children aged 6 to 13.5 years, from two rural Aboriginal settlements and one rural Caucasian school (Hawker) provided evidence of significant deficits in one of the Aboriginal settlements (Yalata). Yalata Aboriginal children had lower body weights and heights for age and lower intracellular water values. Plasma albumin, zinc, iron, alpha-tocopherol, beta-carotene and retinol concentrations were lower relative to the normally grown Aboriginal children at Nepabunna. The latter children did not differ from rural Caucasian children for the parameters studied. The reasons for this poorer growth at Yalata may reside in poor nutrition, or repeated bowel infection in postnatal life leading to malabsorption, or both. Limited observational evidence suggests that Giardiasis has a high prevalence at Yalata, and it has been shown elsewhere that Giardiasis is capable of inducing malabsorption with resulting nutritional deficiencies.

Adolescent↗
PubMed1988

Effect of iodine deficiency on craniofacial growth in young common marmosets (Callithrix jacchus).

The effects of iodine deficiency on general and craniofacial growth were determined in young common marmosets. Examinations, including direct measurement, cephalometric radiology, and dental examination, were performed at three-month intervals from birth to 1 year on a cross-sectional sample of three groups of marmosets. The groups were those on a normal diet, n = 50; an iodine-deficient diet during gestation and for 1 year postnatally, n = 26; and an iodine-deficient diet only during gestation (returned to a normal diet at 1 month after birth), n = 18. The iodine-deficient animals were smaller in all dimensions, compared with controls, but they did not have typical cretin facies. Animals that were iodine deficient during gestation but subsequently fed a normal diet were small initially but displayed compensatory growth, so that by 1 year they were nearly normal in size.

Age Factors↗
PubMed1988

Hypocholesterolaemic effects of dietary propionate: studies in whole animals and perfused rat liver.

In adult male rats fed a non-purified diet supplemented with 5% sodium propionate, plasma cholesterol concentrations were significantly depressed. Although liver cholesterol was increased by feeding propionate, rates of hepatic cholesterol and fatty acid synthesis were unchanged. Tissue concentrations and rates of synthesis of cholesterol were also unaffected by dietary propionate in stomach, small intestine and caecum. Concentrations of propionate in hepatic portal venous plasma were raised by feeding the supplemented diet but the increase was low in comparison to the dietary intake. Examination of the gut contents revealed concentrations of total volatile fatty acids (VFA) of 19 mumol/ml in the stomach contents of control rats and 148 mumol/ml (of which propionate contributed 116 mumol/ml) in those fed the supplemented diet. Duodenal and ileal concentrations of VFA were very low and were only slightly raised in the propionate-fed rats while caecal VFA were the same in both groups with a combined mean of 159 mumol/ml. These data indicate that in the rat, the absorption of dietary propionate appears to occur in the stomach. In pigs fed a standard ration hepatic portal venous VFA remained low for the first 4 h after feeding but then rose with the onset of large bowel fermentation. Feeding the diet supplemented with propionate caused hepatic portal venous plasma concentrations to rise by approximately 0.4 mumol/ml. This increase was apparent 30 min after feeding and was sustained for 3 h but subsequently there was no difference to controls. As in the rat, the absorption of dietary propionate appeared to occur in the upper gastrointestinal tract. The transport of propionate via the porcine hepatic portal vein also appeared insufficient to account for the dietary intake and suggests metabolism of the acid by the upper gastrointestinal tract. Further studies with perfused livers from fed rats indicated that propionate at a concentration of 1 mumol/ml did not alter cholesterol synthesis but that inhibition occurred at 18 mumol of propionate/ml. It appears that a redistribution of cholesterol from the plasma to the liver, rather than inhibition of hepatic and intestinal cholesterol synthesis, is responsible for the hypocholesterolaemic effects of dietary propionate. Because the absorption and transport of dietary propionate appears to follow a time course which differs considerably to that of the acid produced by the large bowel microflora, we conclude also that VFA produced by such fermentation would not seem to be responsible for the hypocholesterolaemic effects of certain water-soluble plant fibres.

Animals↗
PubMed1987

Radionuclide angiographic study of the influence of dietary lipid supplements on cardiac function in the marmoset (Callithrix jacchus).

Radionuclide angiography was used to examine the influence of dietary fat on cardiac function in the common marmoset monkey (Callithrix jacchus jacchus) under barbiturate anaesthesia. Animals were fed for 6-8 months with a low fat (4.5%) reference diet or the same diet supplemented (12%) with sunflower seed oil or sheep fat. Although there was a tendency towards increased heart rate, left ventricular ejection fraction, peak ejection rate, and peak filling rate in both fat supplemented groups, significant increases in heart rate (+50%), peak ejection rate (+71%), and peak filling rate (+84%) were found with sheep fat supplementation, whereas only the vegetable oil supplement produced a significant improvement in left ventricular ejection fraction (+23%). There were no differences in resting blood pressure, and the main consequence of dietary fat supplementation was a major increase in apparent cardiac oxygen consumption (+58%) with the sheet fat diet, as determined by the pressure-rate index. Infusion of isoprenaline hydrochloride (0.2 microgram.kg-1.min-1) increased all indices of cardiac function towards common maxima. There were no differences in either the depth or duration of anaesthesia between dietary groups. It therefore is unlikely that this contributed to any of the observed dietary induced differences in cardiac function. It is suggested that dietary saturated animal fat increased cardiac work and oxygen consumption at rest to the extent that functional reserve to respond to stress was significantly diminished. Feeding a linoleic acid rich polyunsaturated vegetable oil supplement was, however, accompanied by evidence of some improvement in left ventricular ejection fraction.

Animals↗
PubMed1987

The influence of linoleate and vitamin E from sunflower seed oil on platelet function and prostaglandin production in the common marmoset monkey.

Vitamin E and linoleate, both of which are found in high concentrations in sunflower seed oil, were examined independently for their influence on general and blood-vascular parameters in vitamin E-deficient common marmosets. A vitamin E-deficient diet (-E, 4 micrograms/g) was supplemented with either 40 micrograms/g vitamin E (+E), vitamin E stripped sunflower oil (+10% SSO-E), or SSO (+10% SSO w/w) in a 2 x 2 factorial designed experiment, and the diets fed for 9 months to 4 even groups of common marmosets. Vitamin E deficiency was associated in marmosets with a loss of skeletal muscle mass and of body weight, enhanced peroxidative haemolysis of erythrocytes, increased white blood cell counts, and in the SSO-E group a relative neutrophilia. Platelet reactivity was increased with vitamin E deficiency, and to a greater degree with the SSO-E group. Aortic prostacyclin production was significantly increased by the addition of vitamin E, linoleate and both as SSO to the deficient diet, the effects being additive. Fatty acid changes associated with the different treatments reflected the influence of high linoleate and vitamin E treatments. The platelet and aortic arachidonate value in the SSO-E group showed the lowest and most variable value, and this was associated with greatest platelet aggregability. An adequate vitamin E intake is essential for stabilising high PUFA diets and biomembranes and enhancing the protective role of prostacyclin in blood vessels against thrombogenesis.

Animals↗
PubMed1987

The occurrence of cardiac lipidosis and necrotic lesions in the hearts of rats following long-term feeding of different lipid supplemented diets.

The effects of "long-term" feeding of different lipid supplemented diets (12% added fat, w/w) on the incidence of lipidosis or the severity of necrosis was examined in the cardiac muscle of male Hooded Wistar rats, after at least 12 months on the diets. The effects of supplementation with either n-6 polyunsaturated fatty acids (PUFA's) added as sunflower seed oil (the SSO diet), or one enriched with n-3 PUFA's added as a low cholesterol, low vitamin (A & D) fish oil preparation obtained from eviscerated Southern Bluefin Tuna (the TFO diet) were compared to those found in the hearts of rats fed either a relatively low fat commercially available stock diet (REF) which contained 4% (w/w) of mixed fats of animal, vegetable and marine origin, or after this stock diet had been supplemented to the same extent by the addition of 12% (i.e. 12:88 g) sheep kidney (perirenal) fat, the SF diet. Extensive cardiac lipidosis was seen after feeding either the TFO or the SF diets, but was not observed in the hearts of experimental rats from either the SSO or REF fed groups. Conversely, in these mature animals, grade 1 necrotic lesions were uniformally found in the cardiac muscles of all rats examined, but neither their incidence nor severity could be attributed to any dietary effect. These necrotic lesions are therefore more probably a reflection of the age of the animals at the time of sacrifice, rather than to any of the dietary supplements employed. Some evidence of "Yellow Fat" disease was found by the presence of lipofuscin pigmentation in the storage fat of rats receiving n-3 PUFA's (the TFO diet) but was not observed in any other dietary group nor in the livers or kidneys of any animals. This extent of storage fat pigmentation was not associated with any retardation of growth in this dietary group.

Adipose Tissue↗
PubMed1986

Mitochondrial membrane fatty acid composition in the marmoset monkey following dietary lipid supplementation.

Diets supplemented with high levels of saturated fatty acids derived from sheep kidney (perirenal) fat or unsaturated fatty acids derived from sunflowerseed oil were fed to marmoset monkeys for 22 wk. The effect of such diets on plasma, red blood cell phospholipids, and liver, heart, kidney and brain mitochondrial phospholipid fatty acids was determined. Despite large differences in the level and type of lipid present in the experimental diets, there was little effect on the proportion of saturated to unsaturated fatty acids in the phospholipids of the membranes examined. The diets did, however, alter the proportion of the various classes of polyunsaturated fatty acids in the membrane phospholipids, with the sunflowerseed oil diet elevating and the sheep kidney fat diet reducing the n-6/n-3 unsaturated fatty acid ratio, relative to a low (mixed fat) reference diet. This change occurred in all membranes except brain, in which only a small response to altered dietary lipid intake was observed. Elevation of dietary linoleic acid led to an increase in membrane linoleic acid and a marked decrease in membrane arachidonic acid, such that the membranes from animals fed the sunflowerseed oil diet exhibited the lowest proportion of arachidonic acid. In this latter respect, the response of the marmoset monkey to dietary lipid supplementation differs markedly from the rat. Our inability to alter significantly membrane lipid saturation/unsaturation supports the notion that a homeostatic mechanism is in some way responsible for buffering membranes from the effects of significant changes in the nature of the dietary lipid intake.

Animals↗
PubMed1986

The effect of maternal thyroidectomy prior to conception on foetal brain development in sheep.

Merino ewes were surgically thyroidectomized, and mated 6 weeks later when their plasma thyroxine (T4) levels were negligible. Their foetuses were delivered by hysterotomy at 52, 71, 84, 98, 125, 140 days gestation or at term (150 days). Despite the very low levels of T4 in maternal plasma, the concentrations of T4 in foetal plasma were not significantly different after 71 days gestation from those of foetuses of sham-operated (control) ewes. Foetal brain and body weights, however, were reduced from 71 days compared to those of foetuses of sham-operated ewes. The foetal brain weights but not the body weights were restored to normal from 125 days to term. In addition to the weights, cell number (DNA) and cell size (protein:DNA ratio) appeared to be normal in the neonatal brain at parturition and this was confirmed by histological examination of the brains. Thus lack of maternal thyroid hormones in early pregnancy may cause a reduction in brain and body growth in the foetus which, in the case of the brain, appears to be restored to normal after the onset of foetal thyroid function.

Animals↗
PubMed1986

Thermotropic interaction of vitamin E with dimyristoyl and dipalmitoyl phosphatidylcholine liposomes.

The effect of vitamin E on the thermal behavior of two saturated phosphatidylcholines was investigated by differential scanning calorimetry. For dimyristoyl and dipalmitoyl phosphatidylcholines, the addition of vitamin E at concentrations of 1, 5 and 10 mol% vitamin E, resulted in a lowering of the phase transition temperature and a broadening of the temperature range of the phase transition indicating an increase in the fluidity of the phospholipids. Taken together with other physical studies on the effect of vitamin E on (unsaturated) phospholipids, these results indicate that vitamin E could influence the physical properties of membrane phospholipids in addition to its known antioxidant role. The likelihood of this interaction would be enhanced if vitamin E was not randomly distributed in biological membranes but rather was located in domains where its local concentration, relative to phospholipids, was elevated.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1985

The influence of dietary fats on plasma lipids, blood pressure and coagulation indices in the rat.

Male Hooded Wistar rats were fed a commercial rat diet supplemented 12% by weight with sheep fat, sunflower seed oil and fish oil (tuna) over a period of 8 months. The influence of these diets on plasma fatty acids, triglycerides and cholesterol, blood pressure, body weight and coagulation indices was assessed. The sheep fat (SF)-fed rats showed a significant increase in body weight over the reference group (C) of 18%, and systolic blood pressure increased by 9.4%, whereas other dietary groups were not significantly affected. The fish oil (TFO)-fed rats showed a significant lowering of plasma cholesterol (-16.6%) and triglyceride (-47%) relative to the reference group, while the sunflower seed oil (SSO) group showed only a lowered plasma triglyceride (-32%). Plasma fatty acids in general reflected closely the dietary fatty acids, with some exceptions. Coagulation indices provided a consistent picture of an increased tendency to thrombosis in SF-fed rats and a significantly reduced tendency in the TFO-fed rats relative to reference rats. Fish oil rich in 20:5 and 22:6 omega 3 long-chain polyunsaturated fatty acids and low in cholesterol appears to have advantages in terms of reducing those parameters identified as risk factors for coronary heart disease in man. Sheep fat supplements rich in saturated fatty acids produce the opposite trend.

Animals↗
PubMed1985

Changes in fatty acid composition of the cardiac phospholipids of the cotton-eared marmoset (Callithrix jacchus) after feeding different lipid supplements.

After feeding marmosets different lipid supplements for 6 months, the distribution of phospholipid classes and the fatty acid composition of phosphatidylcholine (PC), phosphatidylethanolamine (PE) and diphosphatidylglycerol (DPG) were determined in their cardiac membranes. Supplementing the diet with linoleic-acid-rich sunflower seed oil raised the level of 18:2,n-6 in both PC and PE, but did not change the level significantly in DPG. When 18:2,n-6 was increased, the level of arachidonic acid (20:4,n-6) was significantly decreased in PC and PE. No arachidonic acid was present in DPG. Supplementing the diet with mutton fat did not markedly increase the level of saturated fats, nor did it markedly reduce the level of arachidonic acid in any phospholipid component. No dietary treatment altered the distribution of the major phospholipid classes.

Animals↗
PubMed1985

Effects of wheat bran and porridge oats on hepatic portal venous volatile fatty acids in the pig.

Adult male pigs (40-60 kg of body weight) of the Kangaroo Island strain were surgically implanted with chronic indwelling hepatic portal venous cannulae. After a 24-hour fast the animals were given meals containing 500 g of either wheat bran or porridge oats and 200 g of sucrose and 2 litres of milk. With both cereal preparations plasma volatile fatty acids rose in the hepatic portal vein but the increase was significantly greater with wheat bran. Omission of sucrose and milk did not alter the response to porridge oats but diminished the response to wheat bran. These changes in plasma volatile fatty acids were unaffected by prior cooking of the cereals with hot water. With all test meals acetate and propionate were the major acids found, with butyrate contributing less than 8% of the total. This compositional profile was also found when the pigs were fed a commercial ration. The absence of butyrate differed from observations in the rat and reflected low concentrations of this acid in large bowel digesta. The difference in the response of the concentration of volatile fatty acids to feeding porridge oats and wheat bran in the pig was also the reverse of that found in the rat. These species differences may be of significance in relation to the choice of animal models for human fibre metabolism.

Animals↗
PubMed1985

Haematological characteristics of the common marmoset (Callithrix jacchus jacchus).

Blood cell indices and parameters of haemostasis were studied in the common marmoset. The majority of the results were similar to those found in man. Differences from man were that the prothrombin time was shorter in the marmoset, higher concentrations of aggregating stimuli were required to cause platelet aggregation, and marmoset platelets did not aggregate under the influence of adrenalin. There was sexual dimorphism evident in the data for fibrinogen concentration and for platelet count, both of which were higher in females than in males. Marmoset platelets were very similar in ultrastructure to those of man.

Animals↗