Biomedical subjects
Publications and source records attributed to R Bickerstaffe.
A woman who had lost two babies, each pregnancy being complicated by eclampsia, and one pregnancy resulting in renal failure; was treated in her fourth pregnancy with heparin and dipyridamole from early pregnancy. A successful outcome of this pregnancy is reported.
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Ewes bearing twins were starved for 10 days during the last month of gestation to induce ovine pregnancy toxaemia (OPT). Glucose turnover was measured by a primed continuous infusion of [U-14C]- and [6-3H]glucose at the end of 10 days of starvation (non-susceptible), or earlier when ewes became recumbent with OPT (susceptible). All ewes were slaughtered at the end of the infusion and hepatocytes were prepared in order to measure glucose production from different substrates. Many of the ewes had dead foetuses when slaughtered. Glucose production rates by hepatocytes with the substrates propionate, lactate or alanine were significantly less from the susceptible ewes than were those from non-susceptible ewes. These low rates were not stimulated by incubation with glucagon (10(-8) M), glutamine or glycerol. Rates of glucose turnover and of hepatic glucose production from all substrates were higher for ewes with dead than with live foetuses. The data support the hypothesis that pathogenesis of OPT is related to an impairment of hepatic gluconeogenesis, and further suggest that, in starved pregnant ewes, maternal glucose production may be restrained in the presence of a live foetus.
The kinetics of glucose cycling in 24 ewes bearing twins were studied 1 month before term by bolus injections of [6-3H]- and [U-14C]glucose. The function representing glucose carbon recycling was determined by deconvolution of the [3H]glucose from the [14C]glucose decay curves in plasma by using the SAAM and CONSAM programs, and a model for kinetics of glucose cycling was developed. The [3H]glucose data were fitted by four compartments, and an additional three compartments were required to explain recycling. The results show that labelled carbon was still recycling to plasma 2 days after the injection of tracer. By contrast, a similar analysis on a non-pregnant sheep, with data taken from the literature, showed that no more material was recycled after 1 day. It appears that a larger fraction (20 v. 5%) of the carbon 6 of glucose recycles in pregnant than in non-pregnant sheep. This presumably reflects the metabolism by the feto-placental unit and the increased rate of glucose metabolism during pregnancy.
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Plasma lipoproteins from normal patients with hyperlipidaemia were separated by electrophoresis and analytical ultracentrifugation and the lipoprotein patterns classified. Electrophoresis suffered from being only qualitative but it was quick, relatively inexpensive and, in combination with plasma cholesterol and triglyceride levels, it classified the majority of plasma samples. Classification was not always definite and more difficult when only electrophoresis or plasma cholesterol and triglyceride levels were used. Analytical ultracentrifugation resolved and quantitated the lipoproteins satisfactorily and all the samples were classified. This method was indispensible for definitive analysis of borderline and difficult cases but the cost of the equipment precludes its use in routine clinical practice.
Intravenous glucose tolerance tests were undertaken on fed twin-pregnant ewes at about 120 days of gestation by injecting 0.4 g glucose per kilogram of live weight, then measuring glucose and insulin concentrations in plasma over the next 2 h. An insulin resistance index was calculated from the product of T1/2 for glucose disappearance and the plasma insulin concentrations integrated over time. Approximately 10 days later, the ewes were starved to induce ovine pregnancy toxaemia. During this period, the course of the hypoglycaemia and ketonaemia were followed by measuring metabolite concentrations in jugular blood samples obtained every 2-3 days. The existence of dehydration, acid-base imbalance and renal failure was also determined from packed cell volumes, serum CO2 content and serum concentrations of urea, creatinine and inorganic phosphate. Ewes that became recumbent and moribund with the disease were classified as susceptible whereas those asymptomatic after 10 days were classified as non-susceptible. Seven susceptible ewes had significantly higher insulin resistance indices (2043 +/- 670 s.d.) than did six non-susceptible ewes (1261 +/- 433 s.d.). It was concluded that poor control of glucose homeostasis may be an important predisposing factor in pathogenesis of the disease.
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The relative importance of chylomicrons (Sf greater than 400) and very low density lipoproteins (Sf 20--400) in transporting lipids in lymph was investigated in surgically prepared adult sheep and pre-ruminant lambs fed low fat diets or infused intraduodenally with corn oil. The concentration of triacylglycerol in the intestinal lymph of sheep and lambs was increased from 520 and 925 mg/100 ml to 2326 and 2367 mg/100 ml respectively when corn oil was infused into the duodenum and the ratio of triacylglycerol to phospholipid changed from 3.7 and 5.5 to 9.5 and 9.7 respectively. The flow of lymph also increased. Electron microscopy and analytical and preparative ultracentrifugation showed that lymph lipoproteins from sheep and lambs fed low fat diets consisted mainly of lipoproteins 50 nm in diameter and that very low density lipoproteins (Sf 20--400) contirbuted up to 75% of the Sf greater than 20 lipoproteins. There were no lipoproteins with diameters above 150 nm. Infusion of corn oil into the duodenum of sheep and lambs increased the diameters of lymph lipoproteins. Most were 80--100 nm in diameter but substantial numbers above 150 and up to 400 mn were observed. The maximum contribution of very low density lipoproteins (Sf 20--400) to lipoproteins of Sf greater than 20 was 27--30%. The above findings demonstrate that the size of intestinal lymph lipoprotein particles increases with the amount of lipid absorbed from the small intestines and that the transport of lymph lipids, in ruminants, is similar to that previously found in rats, rabbits and man.
The lipoproteins of density less than 1.063 g/ml of cholesterol-fed rabbits were subjected to analytical ultracentrifugation. In many rabbits two peaks were found in the very low density (Sf greater than 20) portion of the lipoprotein spectrum. They were isolated by preparative ultracentrifugation and analysed. The smaller particles (remnant chylomicrons) had a peak Sf of 37, mean diameter of 36 nm, mean density of 1.00 g/ml, and their chemical composition agreed closely with previous reports. The larger particles had a peak Sf of 270, mean diameter of 80 nm, mean density of 0.97 g/ml and a high (80%) cholesterol ester and low (4%) triglyceride content. The fatty acid composition of the cholesterol esters, phospholipids and triglycerides was similar in both fractions. It is proposed that these large lipoprotein particles are also remnant chylomicrons. Possible reasons are presented to explain the presence of this second peak in the very low density lipoprotein spectrum.
(1) The arterio-venous difference technique, previously used to measure mammary substrate uptake with cows and goats, was used to measure amino acid uptake by the mammary gland of the lactating Merino ewe. Possession of a single large superficial epigastric vein by the Merino ewe makes the Merino breed the most suitable for this type of study. (2) A method was developed enabling hourly measurement of milk yield without causing undue stress. Milk yield was essentially constant over a 7-8 h period. (3) Mammary extraction of most non-essential amino acids was low relative to output in milk protein and showed a greater variability with time than that found for the essential amino acids. There was a significant mammary extraction of ornithine and citrulline, neither amino acid being found in ovine milk protein. (4) Of the essential amino acids valine, isoleucine, leucine and arginine were taken up in excess of their requirement for milk protein synthesis. (5) On the basis of the extent of mammary extraction, methionine, lysine and leucine were first-, second- and third-limiting to the rate of milk protein synthesis. (6) Despite fluctuations in arterial amino acid concentrations the arterio-venous differences of the essential amino acids were relatively constant over a 7-8 h period. (7) The pattern of mammary amino acid uptake in the ewe is contrasted with that found in similar studies carried out with the lactating cow and goat.
(1) The validity of using the arterio-venous concentration difference of methionine to calculate mammary blood flow in the ewe, on the basis of the Fick principle, is discussed. (2) Calculation of mammary blood flow in the lactating Merino ewe indicated that blood flow per unit weight of tissue and the ratio of blood flow : milk yield were approximately twice that found in the lactating cow and goat. (3) Calculated mammary blood flow in Merino ewes was used in conjunction with glucose arterio-venous difference to determine mammary glucose uptake. Glucose uptake per unit weight of tissue in the ewe was almost double that found in the cow and goat. The ratio of mammary glucose uptake to lactose output was also higher in the ewe than that found in the cow and goat. The utilization of glucose by the mammary gland of the ewe is discussed in relation to the possible greater requirement for NADPH and glycerol for milk fat synthesis in this species.
1. Surgically prepared lactating goats were used to obtain quantitative information on the biohydrogenation and absorption of dietary fat, and on the mammary uptake and transfer into milk fat of the complex mixture of cis- and trans-isomers of octadecenoate that arise during ruminal biohydrogenation. 2. About 90% of dietary linolenate, linoleate and oleate was hydrogenated in the rumen, and the availability to the animals of the essential fatty acid, linoleate, represented only 0.5-1.5% of the total dietary energy. 3. The intra-ruminal administration of (14)C-labelled linolenate and linoleate showed that these acids were not absorbed from the rumen, in agreement with previous work. 4. No selectivity was observed in the metabolism of the geometrical and positional isomers of octadecenoate: their rates of absorption from the small intestine, transfer into lymph, uptake by the mammary gland and appearance in milk fat were similar. 5. The desaturase activity of intestinal epithelium was demonstrated by the appearance in lymph of [1-(14)C]oleate after the addition of [1-(14)C]stearate to the small intestine.
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