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Biomedical subjects

D E Hall

Publications and source records attributed to D E Hall.

At least 55 records · Page 3Linked to original sources
PubMed1983

Immune responses to chlorpromazine in rats. Detection and relation to hepatotoxicity.

It has frequently been suggested that the jaundice which occurs in a small percentage of human patients following treatment with chlorpromazine is due to a hypersensitivity reaction. It has, however, proved impossible to obtain an animal model for this condition. We now show that oral administration of chlorpromazine at 25 mg/kg per day to Wistar albino rats results in formation of both humoral and secretory antibodies to chlorpromazine. We also demonstrate that the severity of the hepatic changes observed in chlorpromazine-fed animals (periportal glycogen loss and centrilobular fatty change) is enhanced by preimmunization of the rats via the gut-associated lymphoid tissue with a chlorpramizine-protein conjugate. There was, however, no correlation between the titre of either serum or biliary antibodies in individual animals and the degree of liver damage. Our results therefore suggest than an immune mechanism is indeed implicated in chlorpromazine toxicity but show clearly that toxic symptoms are not a simple consequence of the formation of anti-chlorpromazine antibodies.

Animals↗
PubMed1983

A comparison of the protective effects of N-acetyl-cysteine and S-carboxymethylcysteine against paracetamol-induced hepatotoxicity.

The protective effect of the sulphur-containing amino acids N-acetyl-cysteine and S-carboxymethylcysteine against paracetamol-induced hepatotoxicity was evaluated in the hamster by biochemical and histological methods. Of the animals receiving paracetamol alone 25% died within 24 h following administration. All surviving animals showed acute hepatocellular injury and marked loss of cytochrome P-450 and hepatic mixed-function oxidase activities. Simultaneous administration of N-acetylcysteine decreased the mortality rate, partly prevented the paracetamol-induced liver damage and partly restored enzyme activities. Simultaneous administration of S-carboxymethylcysteine with paracetamol afforded no protection. Kidneys from all animals were histologically normal. Human liver microsomes and liver microsomes from 3-methylcholanthrene-pretreated hamsters metabolished paracetamol to intermediate(s) that bind covalently to microsomal proteins. The rate of covalent binding was inhibited markedly by N-acetylcysteine and to a lesser extent by S-carboxylmethylcysteine.

Acetaminophen↗
PubMed1983

Interorgan metabolism of amino acids in streptozotocin-diabetic ketoacidotic rat.

Amino acid concentrations in whole blood, liver, kidney, skeletal muscle, and brain were measured and arteriovenous differences calculated for head, hindlimb, kidney, gut, and liver in control and streptozotocin-diabetic rats. In the control rats, glutamine was released by muscle and utilized by intestine, intestine released citrulline and alanine, liver removed alanine, and the kidneys removed glycine and produced serine. In diabetic rats, the major changes from the pattern of fluxes seen in the normal rat were the release of many amino acids from muscle, with glutamine and alanine predominating, and the uptake of these amino acids by the liver. Glutamine removal by the intestine was suppressed in diabetes, but a large renal uptake of glutamine was evident. Branched-chain amino acids were removed by the diabetic brain, and consequently, brain levels of a number of large neutral amino acids were decreased in diabetes.

Amino Acids↗
PubMed1982

Effect of 1,3-diaminopropan-2-o1, an inhibitor of ornithine decarboxylase, on the metabolic response of liver to insulin.

The effect of diaminopropanol, an inhibitor of polyamine synthesis, on the metabolic response of liver to insulin was studied in streptozotocin-diabetic rats. Insulin elicited a prompt and very marked increase in ornithine and S-adenosylmethionine decarboxylase activities and in putrescine concentration. Pretreatment of rats with diaminopropanol prevented the increase in the decarboxylases and resulted in decreased spermidine and spermine content of liver. The insulin-induced increase in glycogen content was depressed by 50% and the increase in the rate of lipogenesis in vivo was completely prevented by prior injection of diaminopropanol. These studies implicate altered polyamine metabolism in the metabolic response of liver of streptozotocin-diabetic rats to insulin.

Adenosylmethionine Decarboxylase↗
PubMed1981

Lumbosacral skin lesions as markers of occult spinal dysraphism.

Early treatment of occult spinal dysraphism may prevent progressive neurological deficits. However, diagnosis is often delayed until the onset of irreversible neurological damage. A review of data from the literature and patients at Johns Hopkins Hospital suggests that lumbosacral skin abnormalities such as tufts of hair, hemangiomas, lipomas, skin tags, or pigmented nevi should alert the physician to search for occult spinal dysraphism. In the asymptomatic patient with a skin lesion, roentgenography of the lumbosacral spine is a useful screening procedure for identifying treatable underlying problems.

Adolescent↗
PubMed1980

Polyamine and amino acid content, and activity of polyamine-synthesizing decarboxylases, in liver of streptozotocin-induced diabetic and insulin-treated diabetic rats.

1. Concentrations of polyamines, amino acids, glycogen, nucleic acids and protein, and activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase, were measured in livers from control, streptozotocin-diabetic and insulin-treated diabetic rats. 2. Total DNA per liver and protein per mg of DNA were unaffected by diabetes, whereas RNA per mg of DNA and glycogen per g of liver were decreased. Insulin treatment of diabetic rats induced both hypertrophy and hyperplasia, as indicated by an increase in all four of these constituents to or above control values. 3. Spermidine content was increased in the livers of diabetic rats, despite the decrease in RNA, but it was further increased by insulin treatment. Spermine content was decreased by diabetes, but was unchanged by insulin treatment. Thus the ratio spermidine/spermine in the adult diabetic rat was more typical of that seen in younger rats, whereas insulin treatment resulted in a ratio similar to that seen in rapidly growing tissues. 4. Ornithine decarboxylase activity was variable in the diabetic rat, showing a positive correlation with endogenous ornithine concentrations. This correlation was not seen in control or insulin-treated rats. Insulin caused a significant increase in ornithine decarboxylase activity relative to control or diabetic rats. 5. S-Adenosylmethionine decarboxylase activity was increased approx. 2-fold by diabetes and was not further affected by insulin. 6. Hepatic concentrations of the glucogenic amino acids, alanine, glutamine and glycine were decreased by diabetes. Their concentrations and that of glutamate were increased by injection of insulin. Concentrations of ornithine, proline, leucine, isoleucine and valine were increased in livers of diabetic rats and were decreased by insulin. Diabetes caused a decrease in hepatic concentration of serine, threonine, lysine and histidine. Insulin had no effect on serine, lysine and histidine, but caused a further fall in the concentration of threonine.

Amino Acids↗
PubMed1979

The effect of megadose ascorbate on some haemopoietic factors in the young guinea pig.

The effect of oral administration of megadoses of ascorbate was studied on some haemopoietic factors in young apparently normal guinea pigs. Supplementation of 150 mg of the vitamin for 7 days resulted in significantly increased haematocrit value and haemoglobin concentration. Total and unsaturated iron binding capacity were also increased in association with elevated plasma iron concentration. The difference of these results from the control animals, however, was not statistically significant. The improved haematological status in guinea pigs by ascorbate treatment could be attributed to haemoconcentration rather than to an effect of iron metabolism.

Animals↗
PubMed1978

Polyamine metabolism in liver of young rats.

Rat liver undergoes a phase of rapid growth during weaning. We followed the changes in polyamine metabolism occurring during this period of natural growth, and compared them with changes in DNA and RNA accumulation. There was a 2.5-fold increase in the number of cells per liver between suckling (18--19 days old) and weaning (30--32 days old) rats. Ornithine decarboxylase activity increased from the low value in 18-day-old rat pups and remained significantly higher (approx. 5--10-fold) than that in adult rats from day 21 to day 34. Putrescine-dependent S-adenosylmethionine decarboxylase activity was slightly but significantly increased during most of this period. Spermidine and RNA concentrations fluctuated in concert, whereas spermine content per cell doubled during the period from day 23 to day 30.

Adenosylmethionine Decarboxylase↗
PubMed1978

Analysis of spermidine and spermine in rat liver. Effect of hypophysectomy on polyamine concentrations.

A simple, rapid, reproducible assay for tissue polyamines using a standard unmodified amino-acid analyzer is described. This technique will allow accurate measurement of the polyamines from as little as 10 mg of liver in less than 1 h. We have used this method to establish the optimum conditions for the extraction of polyamines from liver and to study the effects of hypophysectomy on polyamine content of rat liver. Hypophysectomy caused a fall in RNA, protein, putresine, and spermidine content prevented the normal increase in spermine in rat liver seen with increasing age.

Aging↗
PubMed1976

Arteriovenous differences for amino acids and lactate across kidneys of normal and acidotic rats.

1. Arteriovenous differences fro amino acids across kidneys of normal and chronically acidotic rats were measured. Glutamine was the only amino acid extracted in increased amounts in acidosis. There was a considerable production of serine by kidneys from both normal and acidotic rats. 2. The arterial blood concentration of glutamine was significantly decreased in acidotic animals. 3. The glutamine extracted by kidneys of acidotic rats was largely and probably exclusively derived from the plasma. 4. The blood lactate concentration was unchanged in acidosis, as was the uptake of lactate by the kidney.

Acidosis↗
PubMed1976

Prophylaxis in haemophilia: a double-blind controlled trial.

A double-blind controlled trial of prophylactic factor VIII therapy has been carried out on nine severe haemophiliacs at the Lord Mayor Treloar College. Infusions were given once weekly and calculated to give a post-infusion plasma concentration of at least 0.25 I.U./ml of factor VIII. This regime reduced the overall bleeding frequency by 15%. The bleeding frequency in the first 3 days post-infusion was reduced by 66%. A moderate overall reduction in morbidity was also achieved. It is calculated that to reduce the incidence of bleeding in severe haemophiliacs by 15% would require a 73% increased usage of therapeutic materials. More than twice this amount of material is likely to be needed to reduce the bleeding frequency of the same group by 66%.

Adolescent↗