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Biomedical subjects

T J French

Publications and source records attributed to T J French.

At least 37 records · Page 2Linked to original sources

Control of tissue carnitine contents: effects of partial hepatectomy and liver regeneration on carnitine concentrations in liver and extrahepatic tissues of the rat.

The liver is the sole site of carnitine biosynthesis in the rat. However, the first 24 h after the surgical removal of two-thirds of the liver mass are not associated with depletion of carnitine either in the liver remnant or in a number of extrahepatic tissues with relatively short turnover times of carnitine (less than 24 h; heart, spleen, kidney). Dietary carnitine was not supplied. The results suggest that the capacity of the remnant liver for carnitine biosynthesis is sufficient to maintain tissue carnitine contents. Liver regeneration influenced the relative proportions of hepatic free and acylated carnitines in a manner compatible with changes in fat disposition in the proliferating tissue.

Animals↗

Effects of dexamethasone on carnitine metabolism in liver and extrahepatic tissues.

The in vivo effects of dexamethasone administration on liver and extrahepatic tissue carnitine concentrations were assessed in 48-h-starved rats. In heart and kidney, but not in liver, dexamethasone significantly increased total carnitine concentration. Acute (2.5 h) treatment with 2-tetradecylglycidate (TDG), a specific inhibitor of carnitine palmitoyl transferase 1, not only increased total hepatic carnitine concentrations, but also permitted an effect of dexamethasone (a further increase in hepatic carnitine concentration). The results are discussed in terms of acute (substrate-mediated) and chronic (hormonal) control of carnitine turnover.

Animals↗

Carnitine metabolism in livers and hearts of 48h-starved rats: the contribution of fat and carbohydrate to acylcarnitine formation.

The work investigated the effects of administration of 2-tetradecylglycidate (TDG), an inhibitor of mitochondrial long-chain fatty acid oxidation, alone or in combination with glucose, on concentrations of free and acylated carnitine in livers and hearts of 48 h-starved rats. The only significant effect of TDG in the heart was to decrease [short-chain acylcarnitine]. This demonstrates that in heart, fat oxidation is linked to the formation of short-chain acylcarnitine. Cardiac [short-chain acylcarnitine] was not significantly decreased by TDG if the rats were also administered glucose, suggesting that acyl CoA derived from glucose may be used for short-chain acylcarnitine formation in TDG-treated rats. TDG significantly decreased in [free carnitine]. No changes in [short-chain acylcarnitine] were observed. This indicates that formation of short-chain acylcarnitine in liver is not determined by the rates of fat oxidation. It was calculated that at least 63% of the acyl-groups esterified to carnitine were generated by intramitochondrial beta-oxidation. The effects of glucose and TDG on hepatic concentrations of free and long-chain acylcarnitine were additive, suggesting that extramitochondrial fat oxidation can contribute to acylcarnitine formation in liver.

Animals↗

A modified cows' milk formula suitable for low birthweight infants.

Low birthweight babies fed standard modified cows' milk formulae are at risk from the high fluid intake needed for adequate nutrition, and very preterm babies often develop late hyponatraemia if the sodium intake fails to match large renal losses. A new cows' milk formula (Cow and Gate Prematalac) provides 120 kcal, 3.6 g protein, 7.5 g fat, and 4 mmol sodium in 150 ml. Ten low birthweight babies were fed the new formula at 150 ml/kg a day and compared with 12 similar babies fed a standard modified cows' milk formula (Wyeth SMA Gold Cap) at 180 ml/kg a day. All the babies grew at intrauterine rates and there was no difference in clinical course. None fed the new formula developed hypernatraemia, oedema, or dehydration and none fed the standard formula developed hyponatraemia. The Prematalac group safely excreted the increased osmotic load and had a higher urinary sodium concentration which should protect less mature preterm infants from late hyponatraemia.

Animals↗

Sideroblastic anaemia associated with iron overload treated by repeated phlebotomy.

Iron overload with prominent skin pigmentation and hepatic parenchymal siderosis is reported in a patient with refractory sideroblastic anaemia. Failure to reverse the sideroblastic changes or the anaemia with conventional therapy prompted us to use a graded phlebotomy programme. The rising haemoglobin level in spite of repeated venesections is support for this approach in selected patients with this diagnosis.

Aged↗

The effect of vasopressin upon the excretion of calcium by the sheep.

Vasopressin (140 muU/min) was infused intravenously into 12 conscious merino ewes for 2 hr. Urine flow rate and free water clearance were consistently reduced. There was no effect upon renal plasma flow, glomerular filtration rate or the rate of excretion of sodium, potassium, magnesium, chloride or phosphate. Although all animals received 75 mmol calcium chloride into the rumen on the previous day, five commenced the experiment with calcium excretion rates of less than 1 mumol/min. In these, vasopressin further decreased calcium excretion. In seven animals with calcium excretion rates between 2 and 20 mumol/min vasopressin had no effect upon either total calcium or free ionized calcium excretion rate.

Animals↗

The acute effects of intravenous infusion of parathyroid hormone on urine, plasma and saliva in the sheep.

Following an intravenous loading injection of 75 U.S.P. Units of Para-Thor-Mone (Eli Lilly and Co), seven conscious, non-pregnant, non-lactating Merino ewes were infused with a maintenance dose of the hormone at a rate of 4-75 U.S.P. units/min for 2 hr. The classical hypercalcaemia and hypophosphataemia of the non-ruminant was observed, but the hypercalcaemi- was only small. Plasma potassium concentration decreases, while there were no changes in plasma sodium, chloride or mangesium. The classical phosphaturic effect of the hormone was not observed, only trace amounts of phosphate being exreted throughout the experiment. Urinary excretion of calcium and magnesium decreased, urine flow and urinary excretion of sodium, potassium, chloride, bicarbonate and urine pH increased. Glomerular filtration rate was unaffected, but renal plasma flow increased. The concentration and secretion rate of salivary phosphate increased markedly. Changes in the other important salivary electrolytes (sodium, potassium, chloride, bicarbonate and hydrogen ion) also occurred, but it was difficult to separate primary from secondary effects of the hormone. Saliva flow rate increased transiently following hormone injection, but the effect was not sustained by the maintenance infusion.

Animals↗

Changes in renal haemodynamics and electrolyte excretion during acute hyperkalemia in conscious adrenalectomized sheep.

The p-aminohippurate (PAH) clearance, inulin clearance and the excretion of electrolytes by 10 adrenalectomized sheep were measured before, during and after the infusion of 0-43 M-KCl at 2 ml./min for 2 hr. The PAH clearance increased as the plasma potassium concentration increased up to approximately 6-0 m-mole/l. Further increases in plasma potassium were associated with a progressive return of the PAH clearance to or below the pre-infusion levels. At its maximum the PAH clearance was 1-228 +/- 0-032 (S.E. of mean) times the pre-infusion levels. The inulin clearance increased to reach a mazimum coincident with or subsequent to the maximum PAH clearance. The maximum level of inulin clearance during the hyperkalaemia was 1-158 +/- 0-020 times the pre-infusion clearance. The increments in the clearance of potassium and of bicarbonate rose rapidly to exceed the increment in inulin clearance during the hyperkalaemia in all experiments. The increments in the clearance of sodium and of chloride exceeded the increment in inulin clearance in more than half the experiments. It was concluded that although hyperkalaemia was associated with increased glomerular filtration much of the increased excretion of sodium, chloride and bicarbonate was derived from depressed tubular reabsorption of the ions. When the infusion experiments were repeated on the same animals the sheep demonstrated an improved ability to control the rise in plasma potassium concentration which was similar to potassium adaptation described in other species. There were no apparent differences between sheep maintained on 1-5 mg and 5 mg deoxycorticosterone acetate daily in their adaptation to potassium loading and the effect was tentatively attributed to the level of steroid maintenance being chronically high. The toxicity of hyperkalaemia was not lessened by this adaptation to potassium loading.

Adrenalectomy↗