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Biomedical subjects

R C Fishlock

Publications and source records attributed to R C Fishlock.

9 recordsLinked to original sources
PubMed1989

An animal model of systemic carnitine deficiency produced by haemodialysis of sheep.

1. Sheep, which had previously been surgically prepared with cannulae in various vessels to monitor substrate and metabolite exchanges across all the major organs, were connected to a haemodialysis machine and their blood was dialysed at an average rate of 6.23 ml/min/kg body weight. 2. Dialysis for 4 hr reduced the blood free carnitine concentrations to approx. 50% of the initial values and the concentrations returned to the initial values after 18 hr recovery. 3. Carnitine balance studies showed that approx. twice the amount of carnitine lost from the blood during dialysis passed into the dialysate indicating that carnitine was also lost from the extracellular fluid. 4. The average blood concentration of short-chain acylcarnitines did not vary significantly during dialysis or during the recovery phase. However, an output of short-chain acylcarnitines by the liver at 3 and 18 hr recovery and an uptake by the hind-body at 18 hr recovery was observed. 5. These results suggest that haemodialysis of sheep provides a useful model of systemic carnitine deficiency and suggest that treatment with acetylcarnitine or propionylcarnitine could be an efficient means of supplying carnitine in carnitine replacement therapy.

Animals↗
PubMed1989

Partial purification and properties of the isozymes of S-adenosylmethionine synthetase from sheep liver.

Three forms of AdoMet synthetase were separated from sheep liver. The apparent molecular weights of the native isozymes were 122,000, 62,400 and 70,800 for the alpha-, beta 1- and beta 2-form, respectively and beta 1 was the predominant form. The alpha-form exhibited negative cooperativity with [S] 0.5 values of 31 microM for methionine and 62 microM for ATP; while the two beta-forms exhibited positive cooperativity with [S]0.5 values for methionine of 82 microM and 70 microM and those for ATP of 572 microM and 505 microM for the beta 1- and beta 2-form, respectively. Dimethylsulfoxide markedly stimulated the activities of the two beta-forms at low methionine concentrations. However, at high methionine levels, it inhibited the activity of the beta 2-form but not that of the beta 1-form. The effect of dimethylsulfoxide on the alpha-form was not significant. AdoMet was inhibitory at high concentrations. However, it had a slight stimulatory effect on the two beta-forms at low concentrations when methionine level was also low. These results suggest that AdoMet synthetase is a regulatory enzyme and the reaction rate in vivo can be directly influenced by substrate and product concentrations.

Animals↗
PubMed1988

Determination of creatinine in whole blood, plasma, and urine by high-performance liquid chromatography.

A sensitive method for the specific determination of creatinine in whole blood, plasma, and urine with high precision and accuracy is described. Samples were deproteinized by addition of acetonitrile and analyzed by high-performance liquid chromatography using a cation-exchange column with a mobile phase of 9% acetonitrile in 40 mM ammonium phosphate (pH 4.0). The recoveries of creatinine added to blood and plasma were almost complete, ranging from 99 to 101%. The coefficients of variation were very small, 1.6% for blood and plasma and 1.5% for urine. Samples can be assayed in 11-min intervals subsequent to the initial injection. As little as 2 microliter of blood or plasma or 0.02 microliter of urine is sufficient for chromatographic analysis. The present method was successfully used for the accurate measurement of small arterial-venous differences of creatinine concentrations in blood across body organs and showed that in the sheep creatinine is produced in the muscles and is excreted by the kidneys. The method is also suitable for routine analysis of creatinine in clinical laboratories.

Animals↗
PubMed1988

Quantitative study on creatine metabolism in sheep tissues.

Creatine metabolism was quantitated in sheep tissues by measurement of the amount of creatine and creatinine flowing into and out of various tissues using multi-catheterized sheep. The results showed that sheep derived no creatine from the digestive tract. The total renal clearance of creatine plus creatinine was about 18 mmoles per day. Daily creatine synthesis in the sheep was some 15 mmoles, of which 80% occurred in the liver. There was a daily uptake of about 5.4 mmoles of creatine and an output of 7.8 mmoles of creatinine by the hindlimbs of the sheep. This difference suggests that the skeletal muscle may be able to synthesize a significant amount of creatine. However, creatine metabolism in the heart, lung and brain was much less active.

Animals↗
PubMed1984

Dependence on blood acetate concentration of the metabolic effects of ethanol in perfused rat liver.

In livers from fed rats perfused with recirculating blood, infusion of ethanol produced an inhibition of ketogenesis followed by substantially increased production. Perfusate lactate concentrations fell markedly following the increase in ketone body formation. In these experiments perfusate acetate rose continuously, reaching a concentration of 10 mM at 70 min, while in a control liver concentrations remained very low. During non-recirculating perfusion with 3 mM acetate there was output of lactate, whereas at 10 mM acetate ketogenesis was greatly stimulated and there was net lactate uptake. These data support the concept that there is a concentration of acetate in the region of 5 mM, below which it competes with lactate for lipogenesis. Above this level acetate may penetrate the mitochondrion and stimulate ketogenesis and gluconeogenesis. Effects of ethanol in vitro may depend on the concentrations of acetate attained in the experimental system.

Acetates↗
PubMed1984

Sources of error in determinations of carnitine and acylcarnitine in plasma.

Radioactive and nonradioactive L-carnitine and acyl-L-carnitine were used to evaluate the washing procedures used during the determination of free, total, short-chain, and long-chain acylcarnitine in human and sheep plasma. The volume of fluid trapped by the protein precipitated by perchloric acid is approximately 24% of the total fluid volume and thus contains 24% of free carnitine and short-chain acylcarnitine. Washing twice with distilled water removes about 25% of the long-chain acylcarnitine along with the trapped free carnitine and short-chain acylcarnitines. Washing the pellet twice with a 60 g/L solution of perchloric acid completely removes the trapped free carnitine and short-chain acylcarnitine but does not remove the bound long-chain acylcarnitines. Thus washing with perchloric acid is essential for accurate measurement of long-chain acylcarnitines in plasma samples.

Acetylcarnitine↗
PubMedDate not supplied

Carnitine deficiency with hyperbilirubinemia, generalized skeletal muscle weakness and reactive hypoglycemia in a patient on long-term total parenteral nutrition: treatment with intravenous L-carnitine.

Low levels of plasma carnitine and reduced urinary carnitine excretion with persistently elevated plasma bilirubin levels, reactive hypoglycemia and generalized skeletal muscle weakness are described in a patient requiring long-term total parenteral nutrition (TPN). Intravenous administration of L-carnitine at 400 mg/day for 7 days and subsequently a maintenance dose of 60 mg/day corrected the plasma carnitine deficiency and reactive hypoglycemia and was associated with a return to normal plasma bilirubin levels and a restoration of skeletal muscle strength.

Adult↗
PubMedDate not supplied

Carnitine balance and effects of intravenous L-carnitine in two patients receiving long-term total parenteral nutrition.

Two patients requiring total parenteral nutrition for 34 and 39 months, had plasma and urinary carnitine assays and plasma lipid assays performed before and during intravenous administration of 400 mg (2500 mumol) of L-carnitine for 7 days, followed by 40 mg (240 mumol) daily continuously. One patient had generalized lethargy and weakness which resolved within the first 5 days of carnitine administration. The plasma-free carnitine levels in this patient rose significantly. The other patient was asymptomatic and while there was no significant change in the plasma-free carnitine levels during carnitine administration, this patient remained in positive carnitine balance throughout the study. There were no significant changes in plasma lipid levels in either patient. In adult patients requiring long-term total parenteral nutrition who are otherwise normal, intravenous L-carnitine may be required to supplement the patients endogenous carnitine production.

Adult↗