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Biomedical subjects

D H Williamson

Publications and source records attributed to D H Williamson.

At least 19 recordsLinked to original sources
PubMed1992

Hepatic blood flow and metabolism in severe falciparum malaria: clearance of intravenously administered galactose.

1. Hypoglycaemia and lactic acidosis are important manifestations of severe falciparum malaria. To investigate hepatic gluconeogenesis in acute falciparum malaria, liver blood flow and galactose clearance were estimated in seven adult patients with moderately severe infection and seven patients with severe infection (three of whom died later). Nine patients were restudied in convalescence. 2. Liver blood flow, determined from the plasma clearance of Indocyanine Green, was lower in acute illness than in convalescence [16.1 (7.0) versus 23.9 (7.2) ml min-1 kg-1, mean (SD)], but this difference was not statistically significant (P = 0.15). There was a significant inverse correlation between admission venous plasma lactate concentrations and the liver blood flow estimated from the clearance of Indocyanine Green (rs = 0.71, P = 0.004). 3. The plasma clearance of galactose after intravenous injection was similar in the acute [15.4 (4.90) ml min-1 kg-1] and convalescent study [12.8 (2.1) ml min-1 kg-1]. The ratio of galactose clearance to Indocyanine Green clearance was significantly higher in acute disease [1.41 (0.51)] than in convalescence [0.70 (0.34)], largely because of the elevated ratios in severely ill patients [1.48 (0.50)]. 4. The rise in blood glucose concentration after galactose administration was significantly higher during acute illness [1.48 (0.72) mmol/l] than in convalescence [0.67 (0.41) mmol/l, P = 0.022], but the insulin response was similar, indicating reduced tissue insulin sensitivity. There was no significant change in the plasma concentrations of other metabolites (lactate, pyruvate, alanine and triacylglycerol) in either study. 5. These results suggest that the segment of the glycolytic pathway between galactose and glucose is unimpaired in patients with severe falciparum malaria.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1992

Acute administration of tumour necrosis factor-alpha or interleukin-1-alpha does not mimic the hypoketonaemia associated with sepsis and inflammatory stress in the rat.

1. Administration of tumour necrosis factor (cachectin) and of interleukin-1-alpha increased the plasma level of nonesterified fatty acids in fed rats, and in the case of interleukin-1-alpha the blood glycerol level was also increased, suggesting stimulation of adipose tissue lipolysis. There were parallel increases in the plasma level of triacylglycerols. Neither cytokine had significant effects on blood or liver total ketone body (acetoacetate plus 3-hydroxybutyrate) concentrations. 2. In starved rats, the higher plasma non-esterified fatty acid concentration was not increased further by the cytokines. The plasma triacylglycerol level was increased, although the absolute change was less than in fed rats. The ketonaemia associated with starvation tended to be increased by the cytokines, but this was only significant in the case of interleukin-1-alpha. Parallel changes occurred in hepatic ketone bodies. 3. It is concluded that tumour necrosis factor-alpha and interleukin-1-alpha are not responsible for the hypoketonaemia associated with sepsis or other inflammatory states.

Animals↗
PubMed1992

Platelet-activating factor causes hypoketonaemia in starved rats.

1. The aim of this work was to examine whether platelet-activating factor could mimic the hypoketonaemia seen in septic and endotoxic experimental animals. Platelet-activating factor was administered either by the intraperitoneal (high dose) or intravenous (jugular vein, low dose) routes. 2. Intraperitoneal injection of platelet-activating factor (25 micrograms/kg body weight) decreased the blood ketone body concentration (acetoacetate plus 3-hydroxybutyrate) transiently (30 min after injection) in starved rats. Continuous intravenous infusion of platelet-activating factor (40 ng min-1 kg-1 for 5 h) caused comparable hypoketonaemia. 3. The hepatic acetoacetate concentration also decreased transiently after injection of platelet-activating factor and there was an increase in the 3-hydroxybutyrate/acetoacetate ratio. The hepatic ATP concentration decreased at 15 and 30 min after injection of platelet-activating factor. Infusion of platelet-activating factor caused a similar decrease in hepatic ketone body concentration, but no significant change in the 3-hydroxybutyrate/acetoacetate ratio or adenine nucleotide concentrations. 4. Platelet-activating factor administered by infusion, but not by injection, decreased the plasma non-esterified fatty acid concentration. The plasma glycerol concentration also decreased after infusion of platelet-activating factor, suggesting decreased lipolysis in adipose tissue. 5. Changes in plasma insulin concentration or white adipose tissue blood flow did not appear to contribute to the decrease in the plasma non-esterified fatty acid concentration after infusion of platelet-activating factor. However, there was a significant decrease in blood flow to interscapular brown adipose tissue in both the infused and injected groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1979

Interactions in vivo between oxidation of non-esterified fatty acids and gluconeogenesis in the newborn rat.

Metabolic interactions between fatty acid oxidation and gluconeogenesis were investigated in vivo in 16h-old newborn rats under various nutritional states. As the newborn rat has no white adipose tissue, starvation from birth induces a low rate of hepatic fatty acid oxidation. Hepatic gluconeogenesis in inhibited in the starved newborn rat when compared with the suckling rat, which receives fatty acids through the milk, at the steps catalysed by pyruvate carboxylase and glyceraldehyde 3-phosphate dehydrogenase. These inhibitions are rapidly reversed by triacylglycerol feeding. Inhibition of fatty acid oxidation by pent-4-enoate in the suckling animal mimics the effect of starvation on the pattern of hepatic gluconeogenic metabolites. It is concluded that, in the newborn rat in vivo, hepatic fatty acids oxidation can increase the gluconeogenic flux by providing the acetyl-CoA necessary for the reaction catalysed by pyruvate carboxylase and the reducing equivalents (NADH) to displace the reversible reaction catalysed by glyceraldehyde 3-phosphate dehydrogenase in the direction of gluconeogenesis.

Animals↗
PubMed1979

Alterations in the rate of lipogenesis in vivo in maternal liver and adipose tissue on premature weaning of lactating rats: a possible regulatory role of prolactin.

Removal of pups for 24 h from rats at peak lactation decreased 3H2O incorporation into lipid in vivo in mammary gland by 95%, whereas it was increased in liver (77%) and adipose tissue (330%). These increases were prevented by administration of prolactin. Plasma insulin increased 3-fold on weaning and this was partially prevented by prolactin.

Adipose Tissue↗
PubMed1979

Regulation of ketogenesis during the suckling-weanling transition in the rat. Studies with isolated hepatocytes.

The rates of ketogenesis from endogenous substrates, butyrate or oleate, have been measured in isolated hepatocytes from suckling and weanling rats. Ketogenesis from endogenous substrate and from oleate decreased on weaning, whereas the rate from butyrate remained unchanged. It is concluded that the major site of regulation of ketogenesis during this period of development involves the disposal of long-chain fatty acyl-CoA between the esterification and beta-oxidation pathways. Modulators of lipogenesis [dihydroxyacetone and 5-(tetradecyloxy)-2-furoic acid] did not alter the rate of ketogenesis in hepatocytes from suckling rats, and it is suggested that this is due to the low rate of lipogenesis in these cells. Hepatocytes from fed weanling rats have a high rate of lipogenesis and evidence is presented for a reciprocal relationship between ketogenesis and lipogenesis, and ketogenesis, and esterification in these cells. Dibutyryl cyclic AMP stimulated ketogenesis from oleate in hepatocytes from fed weanling rats, even in the presence of an inhibitor of lipogenesis [5-(tetradecyloxy)-2-furoic acid], but not in cells from suckling rats. It is suggested that cyclic AMP may act via inhibition of esterification and that in hepatocytes from suckling rats ketogenesis is already maximally stimulated by the high basal concentrations of cyclic AMP [Beaudry, Chiasson & Exton (1977) Am. J. Physiol. 233, E175--E180].

Animals↗
PubMed1979

Changes in blood glucose and plasma insulin after intravenous galactose in human injury.

1. The increase in blood glucose after intravenous galactose was measured at 6--8 h and 14 days after hip replacement (14 patients) and accidental injury (14 patients). 2. After hip replacement there was a greater rise of glucose after galactose on the day of the operation than on recovery, despite basal hyperglycaemia. This earlier period was also associated with inappropriately low insulin concentrations for the prevailing glucose concentration, and hyperketonaemia (13 out 14 patients). 3. After accidental injury patients with initial hyperketonaemia (nine out of 14) also had a greater rise of blood glucose after galactose than on recovery and had relative insulin deficiency; in contrast those who were initially normoketonaemic (five out of 14) showed a rise in glucose comparable with that after recovery and basal insulin concentrations more appropriate to the existing glucose concentration. 4. It is concluded that in most subjects after injury hepatic glucose release after galactose administration is not suppressed despite hyperglycaemia.

Adolescent↗
PubMed1978

The development of ketogenesis at birth in the rat.

In the suckling newborn rat, blood ketone bodies begin to increase slowly 4h after birth and then rise sharply between 12 and 16h, whereas the major increase in plasma non-esterified fatty acids and liver carnitine occurs during the first 2h of life, parallel with the onset of suckling. In the starved newborn rat, which shows no increase in liver carnitine unless it is fed with a carnitine solution, the developmental pattern of the ketogenic capacity (tested by feeding a triacylglycerol emulsion, which increases plasma non-esterified fatty acids by 3-fold) is the same as in the suckling animal. This suggests that the increases in plasma non-esterified fatty acids and liver carnitine seen 2h after birth in the suckling animal are not the predominant factors inducing the switch-on of ketogenesis. Injection of butyrate to starved newborn pups resulted in a pattern of blood ketone bodies which was similar to that found after administration of triacylglycerols, but, at all time points studied, the hyperketonaemia was more pronounced with butyrate. It is suggested that, even if the entry of long-chain fatty acids into the mitochondria is a rate-limiting step, it is not the only factor controlling ketogenesis after birth in the rat. As in the adult rat, there is a reciprocal correlation between the liver glycogen content and the concentration of ketone bodies in the blood.

Animals↗
PubMed1978

Utlization of D-3-hydroxy[3-14C]butyrate for lipogenesis in vivo in lactating rat mammary gland.

Incorporation of D-3-hydroxy[3-14C]butyrate into lipid in vivo suggests that lactating mammary gland is a major site of ketone-body utilization. The incorporation decreases in short-term insulin deficiency (2h) and on starvation (24h), but increases again on refeeding (2h). The activity of cytosolic acetoacetyl-CoA synthetase parallels the changes in nutritional state, but is not affected by short-term insulin deficiency.

Acetyl-CoA C-Acetyltransferase↗
PubMed1978

Evidence for a reciprocal relationship between lipogenesis and ketogenesis in hepatocytes from fed virgin and lactating rats.

Lipogenesis is increased in hepatocytes from fed lactating rats compared with virgin rats. Inhibition of lipogenesis with 5-(tetradecyloxy)-2-furoic acid resulted in increased ketogenesis from endogenous substrate, but not from oleate. Dihydroxyacetone increased ketogenesis from endogenous substrate, but not from oleate. Dihydroxyacetone increased lipogenesis and esterification of [1--14C]oleate and decreased ketogenesis; these changes were reversed by the inhibitor. The reciprocal relationship between lipogenesis and ketogenesis in hepatocytes from fed rats may be due to alterations in [malonyl-CoA] [McGarry, Mannaerts & Foster (1977) J. Clin. Invest. 60, 265--270; Cook, King & Veech (1978) J. Biol. Chem. 253, 2529--2531], but this mechanism is not considered to be sufficient to explain the increased ketogenesis in starvation completely.

Animals↗
PubMed1978

Evidence for the participation of aspartate aminotransferase in hepatic glucose synthesis in the suckling newborn rat.

Inhibition of liver aspartate aminotransferase by L-2-amino-4-methoxy-trans-3-butenoic acid in the suckling newborn rat causes a decrease in all gluconeogenic precursors from phosphoenolpyruvate to glucose and an accumulation of lactate but not of pyruvate. This suggests that the aspartate shuttle is operative and confirms the quantitative importance of lactate as a gluconeogenic precursor at this time during development.

Alanine↗
PubMed1978

Evidence for a role of insulin in the regulation of lipogenesis in lactating rat mammary gland. Measurements of lipogenesis in vivo and plasma hormone concentrations in response to starvation and refeeding.

Fatty acid synthesis in the mammary gland of lactating rats in vivo was 5-fold higher than in the liver. Starvation decreased fatty acid synthesis in the gland 50-fold, whereas refeeding for 2h completely reversed this change. The plasma insulin concentration decreased 2-fold in starvation and was restored to the fed-rat value on refeeding. Glucagon and prolactin concentrations did not always change in parallel with lipogenesis, suggesting that insulin may be a regulator of this process in the gland.

Animals↗
PubMed1978

An alkaline sucrose gradient analysis of the mechanism of nuclear DNA synthesis in the yeast Saccharomyces cerevisiae.

Using alkaline sucrose gradients the mechanism of DNA synthesis has been investigated in both log-phase and synchronised cultures of the yeast Saccharomyces cerevisiae. DNA synthesis proceeds via a heterogeneous population of single-stranded intermediates between 7 and 60 x 10(6) daltons in size. The size of these molecules and a comparison of their behaviour in log-phase and synchronised cultures suggests they are nascent or completed replicons. The progressive increase in molecular weight of these intermediates during S in synchronous cultures was used as a measure of the rate of DNA synthesis per single strand. During the first half of the period of DNA synthesis in the culture, the observed rate of elongation was 0.82 x 10(6) daltons/min. Later in S, an apparent increase in rate was detected, but this may have reflected the joining of completed replicons. In our gradients the pattern of DNA synthesis in the cell cycle mutants cdc2 and 6, thought to make incomplete or faulty DNA at the restrictive temperature (Hartwell, 1974), closely resembled that of the wild-type.

Cell Cycle↗