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Biomedical subjects

D Kadar

Publications and source records attributed to D Kadar.

34 records · Page 2Linked to original sources
PubMed1978

Enzyme induction following a single dose of amobarbital in dogs.

The elimination of amobarbital in dogs was investigated by injecting various doses of amobarbital into a given animal. At low doses (3 mg/kg) serum levels declined in a first-order fashion. Superficially, at high doses (20 mg/kg) the relationship between serum concentration and time could be quantitatively characterized by simple one-compartment saturable kinetics. Indeed, qualitatively, saturation of the amobarbital-metabolizing enzymes was indicated by a shallower initial slope of the semilogarithmic concentration--time profile at the high than at the low dose. However, in addition, an acute enzyme induction phenomenon was observed which was indicated by a shorter terminal half-life of amobarbital at the high dose than after the low dose and also by a shortening in antipyrine half-life.

Amobarbital↗
PubMed1978

Seasonal variation of aryl hydrocarbon hydroxylase inducibility in human lymphocytes in culture.

The aryl hydrocarbon hydroxylase (AHH) inducibility in lymphocytes from peripheral blood of 92 healthy young subjects was tested during a period of 8 months (November - June). The average AHH inducibility was found to be higher from March to June than from November to February, indicating a seasonal variation. Various other features of lymphocytes in culture also appeared to change with the season.

Adult↗
PubMed1977

A case of deficiency of N-hydroxylation of amobarbital.

It has been shown recently that the overall metabolism of amobarbital in man is essentially under genetic control. The drug normally undergoes two hydroxylation reactions, leading to 3'-hydroxyamobarbital (C-OH) and N-hydroxyamobarbital (N-OH). This paper describes a sibship in which two mothers who are identical twins show a gross deficiency on N-OH elimination in urine. The whole set of sibship data suggests that this deficiency represents a recessive trait controlled by a single pair of allelic autosomal genes which regulate N-OH formation. Several methodical approaches to assess an individual's capacity for N-OH formation are illustrated. There was no evidence of compensatory or concordant regulation of the two hydroxylation reactions. The case of this family illustrates that the functional lack of a biotransformation reaction is almost certain to be overlooked if one measures only the disappearance of a multimetabolized drug and not the appearance of metabolites.

Adolescent↗
PubMed1975

A sudden death associated with the use of sodium nitroprusside for induction of hypotension during anaesthesia.

A death from cyanide poisoning during operation was attributable to the use of approximately 400 mg (10 mg per Kg) sodium nitroprusside as an hypotensive agent. Autopsy cyanide levels of 0.5 mg per cent in blood and 0.3 mg per cent in urine and thiocyanate levels too low to measure in either, suggest an abnormality of cyanide metabolism. The lethal dose of sodium nitroprusside appears to be 7 mg per Kg. A safe regimen would be 3.5 mg per Kg as the anticipated total dose for the period of hypotension. Patients resistant to the full hypotensive effects of sodium nitroprusside, or unable to maintain the level of hypotension, or requiring more than 3.5 mg per Kg to achieve the required effect for the anticipated time, may accumulate toxic levels of cyanide in the blood. Patients with Leber's optic atrophy, tobacco amblyopia and possibly those with other nerve atrophies should not receive sodium nitroprusside or any other cyanide precursor.

Adolescent↗
PubMed1975

Sodium nitroprusside in children: Observations on metabolism during normal and abnormal responses.

Three different responses to sodium nitroprusside as a hypotensive agent during anaesthesia in children are described. A constant high dose (greater than 3 mg/Kg) response to, abnormal resistance to and tachyphylaxis to the drug are recognised and are dangerous and potentially lethal. They are probably related to abnormalities of cyanide-thiocyanate metabolism resulting in cyanide accumulation. The abnormal responses produce metabolic acidosis, an increase in mixed venous oxygen tension and a decrease in arterial mixed venous oxygen content difference. Tachyphylaxis may be due to depletion of endogenous thiosulphate and was reversible by sodium thiosulphate therapy (150 mgm/Kg) in two cases in which it was used.

Adolescent↗
PubMedDate not supplied

In vitro studies of human liver alcohol dehydrogenase variants using a variety of substrates.

Alcohol dehydrogenase (ADH) is genetically polymorphic, and large differences in allele frequencies exist between the major human races. Genetic variants at the ADH2 gene locus include the beta 2-ADH ("atypical" ADH) present in 85% of Orientals and the beta 1-ADH ("normal" ADH) present in 85 to 95% of whites. Although the presence of one or the other of these ADH variants does not significantly affect the rate of ethanol oxidation in the living subject, it may affect that of other substrates. The overall objective of this work was to screen in vitro for ADH substrates which might be differentially metabolized by these ADH2variants in living subjects. In an in vitro screening method using autopsy livers at pH 8.5, the formation or disappearance of NADH at 340 nm was measured before and after exposure to 4-methylpyrazole, an ADH-specific competitive inhibitor. The screening test revealed three new substrates and suggested that alcohol substrates fall into two groups. The majority of substrates belonged to a group which was oxidized at a significantly lower rate by the beta 2-ADH as compared to the beta 1-ADH, but this was not the case for a small group which included ethanol. Subsequent kinetic studies of selected alcohols tended to indicate a uniqueness of ethanol kinetics in that both KM and Vmax favored its oxidation by beta 2-ADH rather than by the beta 1 variant. None of the other seven tested alcohols showed a similar differential. Also, reduction of aldehydes and ketones tended to be moderately slower by beta 2- than by beta 1-ADH.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

The fate of [7-3H]isoproterenol in cats after intravenous administration.

The fate of intravenously administered [7-3H]isoproterenol was investigated in cats. Ten minutes after injection the concentration of 3H was highest in the heart, lungs, adrenals, and kidneys, but after 5 hr most of the radioactivity was found in the liver. The concentration of the unchanged drug in the serum declined in a biphasic manner with half-lives of 2.1--2.5 min for the first phase, and 58--77 min for the second phase. The drug was rapidly metabolized to 3-O-methylisoproterenol (MISP) and then conjugated. In 5 hr 44--55% of the administered 3H was excreted in the urine, 2--2.5% as unchanged drug, 21--41% as MISP, and 12--22% as conjugated MISP. Conjugated MISP was also found in the bile. The results indicate that the rate of formation of MISP in cats is much faster than its rate of conjugation and excretion.

Animals↗