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Biomedical subjects

G H McIntosh

Publications and source records attributed to G H McIntosh.

At least 55 records · Page 3Linked to original sources

A comparison of mitochondrial respiration and membrane lipid composition in the rat and marmoset following dietary lipid supplementation.

Rats and marmosets were fed different lipid supplemented diets and the phospholipid fatty acid composition and the respiration rate of liver and heart mitochondria were determined. For both species, diets of differing lipid saturation had little effect on the ratio of saturated to unsaturated fatty acids in the mitochondrial membranes, however the omega 6/omega 3 unsaturated fatty acid ratio was significantly altered by diets of different lipid saturation. In comparison to animals fed low fat diets, mitochondrial respiration in the marmoset was reduced by high fat diets irrespective of the dietary level of lipid saturation. This effect of high fat diets on mitochondrial respiration was not observed for the rat.

Animals↗

Alterations in the dopaminergic system and behaviour in rats reared on iodine-deficient diets.

Male rats raised on an iodine-deficient diet were found to be retarded in growth rate, to have lowered body temperature, and to have poorer memory retention of a passive avoidance task than rats raised on a similar diet but with adequate iodine concentration. In addition, the iodine deficient rats showed increased locomotor activity and sniffing frequency after the dopamine agonist, apomorphine; while their operant performance was inhibited to a greater degree after apomorphine. However, the hypothermic effects of apomorphine were comparable in both iodine-deficient and normal rats. At sacrifice the iodine-deficient rats were found to have significantly depressed thyroxine levels (less than 10% of normal), significantly elevated TSH levels (greater than 700% of normal), and a significantly greater concentration of dopamine receptors in the striatum (28% increase). Thus, rats raised on iodine-deficient diets have considerable behavioural and physiological alterations, including an increased concentration of dopamine receptors.

Animals↗

Ultrastructural detection of the onset of pituitary thyrotroph sensitivity to lowered thyroid hormone concentrations in the fetal sheep.

The goitrogen methylthiouracil was administered orally to pregnant ewes of known gestational ages to induce hypothyroidism in both mother and fetus. Developing pituitary thyrotrophic cells were studied using electron microscopy to detect the earliest gestational age at which morphological changes occurred in response to lowered plasma thyroid hormone concentrations. At 50 days of gestation, the pituitaries of fetuses exposed to the goitrogen were indistinguishable from untreated control glands. However, at 58 days and subsequent ages, "thyroidectomy' cells were observed in pituitaries of all hypothyroid fetuses. These findings indicate that fetal sheep pituitary thyrotrophs are sensitive to lowered thyroid hormone concentrations by 58 days of gestation, suggesting that thyroid-thyrotroph interaction exists at this early stage of development.

Animals↗

Gated blood-pool studies of cardiac function in the rat and marmoset.

To develop a sensitive, relatively noninvasive method for monitoring cardiac function in small laboratory animals, equilibrium gated blood-pool imaging (with Tc-99m RBC) was adapted for use in an inbred strain of laboratory rats of 400-470 g body weight and in marmosets of 320-400 g body weight. A 2-mm pinhole collimator was fitted to the gamma camera to produce a distinct image of the left ventricle following intravenous injection of 5 mCi of pertechnetate. Reproducible and consistent data for heart rate, left-ventricular ejection fraction, and peak ejection rate were obtained from studies on 13 male rats and five marmosets maintained on constant diets. An intravenous injection of 0.4 microgram of isoprenaline led to predictable increases in heart rate, left-ventricular ejection fraction, and peak ejection rate, and provided evidence of the sensitivity of the method in monitoring heart function in small laboratory animals.

Animals↗

Development of a marmoset colony in Australia.

A breeding nucleus of 15 pairs of Callithrix jacchus jacchus was imported from an established colony in the United Kingdom in 1978, and these have now multiplied to 137 animals. Good reproductive efficiency and growth rates have occurred in this colony, with minimal problems from diseases of nutritional or infectious origin. One episode of cessation of breeding and abortions was attributed to excessive noise and disturbance of the normal routine.

Animal Husbandry↗

A physiologic role for the esterified cholesterol transfer protein: in vivo studies in rabbits and pigs.

The observation that pig plasma is deficient in esterified cholesterol transfer activity has been exploited in an attempt to establish an in vivo role for the esterified cholesterol transfer protein. The plasma high density lipoproteins (HDL) of pigs and also of rabbits (a species known to possess an active esterified cholesterol transfer protein) were labeled with 3H in the esterified cholesterol moiety and with 125I in the apoprotein moieties and reinjected into the respective species. In both rabbits and pigs, the removal of 125I from the recipient HDL fraction was parallel to that from the whole plasma, with negligible 125I appearing in other plasma lipoprotein fractions. In the pig, the removal of esterified 3H-cholesterol from the recipient HLD was very similar to that of 125I; there was only minimal appearance in other lipoproteins. In the rabbit, however, there was a major in vivo transfer of esterified 3H-cholesterol from HDL to other fractions. It has been concluded that an active esterified cholesterol transfer protein is probably necessary to achieve the in vivo transfer of esterified cholesterol from HDL to other plasma lipoproteins.

Animals↗

Iodine deficiency and brain development in the rat.

An assessment was made of the influence of low-iodine diet on somatic and brain development at birth (day 0) and 21 days postnatally in the rat. The rat mothers were proven to be iodine-deficient by assay of plasma thyroxine and thyroid stimulating hormone prior to mating, an at 21 days postnatally, when maternal thyroids were removed, weighed and stored for subsequent iodine analysis, along with those of the offspring. There were no significant differences in body weight or brain weight of the offspring at birth, or in the content of DNA or protein. However, at 21 days there was a significant reduction in body weight (21.7%) and whole brain weight (7.9%, P less than 0.2) which was associated with a significant fall n cholesterol content (12.4%, P less than 0.05) and protein level (9.6 %, P less than 0.01), while DNA was not significantly affected (6%). The greatest reduction in weight was seen in the cerebellum. The thyroids in these rats were double normal size, showed follicular cell hypertrophy and absence of colloid histologically, and contained 8% of the iodine content of controls. It is concluded that iodine deficiency retards both somatic and brain development, the change in the latter case being expressed as a reduction in cell size in the cerebral hemispheres and cerebellum, along with reduced myelination throughout the brain.

Animals↗

The Kangaroo Island strain of pig in biomedical research.

The feral pig from Kangaroo Island, South Australia, has descended from British breeds released onto the Island by early explorers approximately 180 years ago. It has developed into a smaller pig than the modern commercial equivalent, with distinctive and reproducible physical characteristics and a physiology which appears to bestow on it some advantages in terms of fitness and vigour. It has adapted easily to laboratory and intensive piggery conditions where it has reproduced satisfactorily. It has a higher erythrocyte count and PCV than the equivalent Large White and a lower white blood cell count. Plasma Na, K and glucose were significantly higher and HCO3 urea and creatinine lower in the Kangaroo Island strain. It represents a useful strain of pig for biomedical research, approaching in size the miniature pigs used overseas. A useful approach to routine bleeding of pigs is described.

Animals↗

Low-iodine diet for producing iodine deficiency in rats.

A low-iodine diet has been prepared for rats, using locally available low-iodine ingredients. On analysis it has been shown to consistently contain 15-20 ng iodine/g. When fed to growing female rats, this diet produced severe iodine deficiency while not significantly affecting growth or reproduction. The deficiency was manifested by a fall in daily urinary iodine excretion (to less than 1 microgram/day) and a seven-fold increase in thyroid uptake (131I) observable within 3 months. Levels of plasma thyroxine (T4) and thyroid stimulating hormone (TSH) continued to change for 4-5 months, T4 falling from 69.9 to 7.5 nmol/l and TSH increasing seven-fold from a control value of 364 to 2406 ng/ml. Goitre was present in all iodine-deficient rats and iodine content in the thyroid was 10% of the control value.

Animal Feed↗

Production of severe iodine deficiency in sheep using a prepared low-iodine diet.

Extensive tests on dietary materials suitable for ingestion by sheep have led to the preparation of an appropriate diet which, when fed to the sheep, caused severe iodine deficiency. The deficiency was manifested by daily urinary excretion values which fell to levels of less than 20 micrograms iodine and by thyroxine (T4) and triiodothyronine (T3) concentrations in blood plasma which were reduced from more than 90 and 1.80 nmol/l to the low levels of less than 2.58 and 0.31 nmol/l respectively. The values were attained 5 months after feeding the low-iodine diet. Goitre was present in most of the animals and the reductions in T4 and T3 values were accompanied by increased concentrations of plasma thyroid stimulating hormone (TSH) from less than 8.6 to more than 68 ng/ml. Samples of wool removed from selected areas of the sheep showed that the iodine-deficient diet also caused a reduction in the growth of wool.

Animals↗

Experimental oxalate urolith formation in rats.

Urinary calculi composed of calcium oxalate were produced in male hooded Wistar rats fed a vitamin B6 deficient diet over 16 weeks. This basic diet was modified by doubling the phosphate content or loading with vitamin C or D3 in three treatment groups. The number of rats developing oxalate stones was not altered by the addition of vitamin D3 or phosphate, but there was a significant increase in total weight of stone formed and histological evidence of extensive renal damage in rats on the high vitamin D3 diet. The addition of vitamin C to the vitamin B6 deficient rats resulted in a reduction in the number of rats with uroliths and a fall in urinary oxalate excretion, while similarly loaded vitamin B6 supplemented controls were free of oxalate calculi. It is concluded that the oxalate urolithiasis induced by vitamin B6 deficiency was exacerbated by added vitamin D3 and reduced by vitamin C.

Animals↗

Urolithiasis in animals.

Urolithiasis is a disease of multifactorial origin. Prominent amongst the causes of disease outbreaks are nutritional factors. Alteration of diet is probably one of the most effective means of prevention, depending of course on the nature of the uroliths formed. In this regard analysis of the stones formed is an essential prelude to understanding, adequately treating the disease and preventing its recurrence.

Animals↗

The influence of parathyroidectomy upon calcium and phosphate homeostasis in adult sheep.

The absorption and secretion of Ca and PO4 were measured with the use of radioactive isotopes in 4 adult sheep before and after parathyroidectomy. Secretion of Ca and PO4 into the stomach and intestines was measured separately. Parathyroidectomy resulted in a negative balance for Ca and PO4 and an accompanying fall in plasma Ca and PO4 concentrations. In the case of PO4 this response was attributed primarily to a reduced intestinal absorption, but for Ca increases in urinary excretion and intestinal secretion also contributed significantly. Secretion of PO4 to the stomach was reduced but endogenous PO4 excretion in the faeces was unchanged which indicated a reduced reabsorption of secreted PO4 by the intestines.

Animals↗

Production of endogenous acetate by the liver in lactating ewes.

The production of endogenous acetate by the liver has been investigated in lactating ewes using animals with indwelling arterial, and portal and hepatic venous cannulae. The capacity of the liver to produce acetate from acetyl-CoA in vitro has also been examined using homogenates prepared from liver biopsy samples. Mean arterial, portal and hepatic venous blood acetate concentrations in four ewes at 4 weeks lactation were 0.40, 1.00 and 1.46 mM respectively. The mean exogenous and endogenous acetate production rates were 56 and 54 mmol/h respectively, giving a total of 110 MMOL/h. The mean portal-hepatic venous difference in free fatty acid concentration was 81 muM. Converting this uptake of free fatty acids by the liver (based on palmitate as a standard) to 2-carbon equivalents, the acetate produced accounted for 70% of the fatty acids taken up. The correlation coefficient (r2) between uptake of free fatty acids and production of acetate by the liver was 0.83 (P less than 0.01). Calculation of the net acetate production in vivo gave a mean value for the production of acetate of 0.75 nmol/min. Calculation of the in vitro enzymic capacity of the liver to produce acetate from acetyl-CoA gave a mean of 0.94 mmol/min. These results indicate that enzymic production of acetate from acetyl-CoA, via carnitine acetyltransferase and acetylcarnitine hydrolase (see Costa and Snoswell 1975a), can adequately account for the substantial production of acetate by the liver in lactating ewes.

Acetates↗

An isotopic study of oxalate excretion in sheep.

Intravenously injected 14C labelled oxalate was rapidly removed from the blood stream via the kidney in 2 sheep, 75% being cleared within 8 h. Mean daily urinary oxalate excretions over 5 days were 21-2 and 27-5 mg and the derived plasma oxalate concentrations were 52-6 and 74-4 mug/100 ml, respectively. Oxalate was both filtered and secreted by the renal tubule with oxalate/inulin ratios varying from 1-11 to 1-57 in 6 normal sheep. A large increase in calcium excretion induced by calcium borogluconate infusion over 5 days was accompanied by a small but consistent increase in urinary oxalate excretion relative to calcium. Oxalate in blood was to be found mainly in the plasma, there being a small (8%) proporation within erythrocytes. This is lower than that reported for man, and yet in its excretion of oxalate via the kidney the sheep appears to closely resemble man and dog.

Animals↗