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Biomedical subjects

D J Morton

Publications and source records attributed to D J Morton.

At least 73 records · Page 4Linked to original sources
PubMed1988

Effectiveness of a therapeutic drug monitoring service as an aid to the control of canine seizures.

The results presented were derived from an anticonvulsant monitoring service, provided for two years to practising veterinary surgeons, in which samples of serum were taken from dogs treated with either primidone or phenobarbitone. Of the 19 patients assessed, 13 were controlled after the recommended changes in dose had been made. Of the six patients not completely controlled after changes in dose, four had a much lower incidence of seizures but two did not respond to treatment in spite of having high serum phenobarbitone levels. There were large variations between the doses of anticonvulsant drugs required to reach therapeutic serum levels; these variations underlined the value of routine monitoring for improving the control of canine seizures.

Animals↗
PubMed1988

Specificity of a colorimetric paracetamol assay technique for use in cases of overdose.

A simple, economical colorimetric procedure for the determination of Paracetamol in serum or plasma (50-450 micrograms/ml) is described. Using the described method it is possible to quantify Paracetamol concentrations within 25 min which makes the technique ideal for use in an emergency-suspected overdose situation. A total of 178 drug/drug combination products were examined for possible interference with the method and of these, eight were shown to interfere significantly with the quantitative assay. However, in all cases it would be possible to correct for the interference to arrive at a semi-quantitative value for Paracetamol concentration by using the absorbance and by comparing the visible colour of the test sample with the Paracetamol standards.

Acetaminophen↗
PubMed1987

Both hydroxy- and methoxyindoles modify basal temperature in the rat.

The various pineal gland tryptophan metabolites were administered to male rats intraperitoneally (100 micrograms/kg) and rectal temperatures were recorded. Of the compounds tested, hydroxytryptophan, N-acetylserotonin, hydroxytryptophol, and their corresponding methoxyindoles all caused a marked hypothermia, indicating that several indolic products may be involved in thermoregulation. Although the brain penetration of indoles is poor, a central site of action would be most likely, although peripheral actions cannot be excluded. The mechanism of induction of hypothermia may involve peptides, the pituitary-thyroid axis, the adrenal gland, or a combination of these. These results may suggest that the pineal gland integrates environmental cues to act in concert with physiological thermostats in the fine tuning of thermoregulation.

Animals↗
PubMed1987

Production of methoxyindoles in vitro from methoxytryptophan by rat pineal gland.

Pineal glands were incubated in the presence of [3H] methoxytryptophan with and without methoxamine, epinephrine, and norepinephrine. The beta-adrenoceptor-stimulated pineal glands were capable of converting methoxytryptophan to methoxytryptamine, melatonin, methoxyindole acetic acid, and methoxytryptophol, albeit in small quantities. Only methoxyindole acetic acid was detectable after incubation of unstimulated and alpha-adrenergic-agonist-treated pineal glands. These results support the proposal that melatonin can be formed from methoxytryptophan although this is a minor synthetic pathway, and the classic pathway from serotonin via N-acetylserotonin should be considered to be responsible for the majority of pineal melatonin production.

Animals↗
PubMed1987

Effect of various cations on the activity of pineal gland N-acetyltransferase (EC 2.3.1.5) and hydroxyindole-O-methyl transferase (EC 2.1.1.4) in vitro.

The effect of various cations on activity of hydroxyindole-O-methyltransferase (HIOMT) and N-acetyltransferase (NAT) from pineal gland was studied. Copper inhibited both enzymes while calcium and magnesium inhibited HIOMT; the mechanisms of these inhibitions are unknown at this stage. Calcium, magnesium, potassium, and sodium initially stimulated NAT activity, and as the cation concentration increased inhibitory activity was observed. These differential effects on NAT activity may in some way be involved in pineal regulation of cation levels.

Acetylserotonin O-Methyltransferase↗
PubMed1987

Mechanism of inhibition of bovine pineal gland hydroxyindole-O-methyltransferase (EC 2.1.1.4) by divalent cations.

The effect of inhibitory cations on hydroxyindole-O-methyltransferase (HIOMT) was investigated in order to elucidate the mechanisms involved. Copper inhibition of HIOMT can be classified as partial, classic noncompetitive inhibition with respect to S-adenosyl methionine and as partial, mixed noncompetitive inhibition with respect to N-acetylserotonin. Binding of copper to the enzyme impaired but did not prevent catalysis, and the difference in inhibitory pattern observed with both substrates may be due to the obligatory order of substrate binding to HIOMT. Calcium and magnesium were uncompetitive inhibitors of HIOMT with respect to both substrates and binding of these cations to the enzyme prevents catalysis. The cations presumably bind to HIOMT in the vicinity of the catalytic site and in some way prevent or impair the catalytic process, possibly by interfering with substrate binding to the enzyme, interfering with methyl transfer or product release after catalysis, or a combination of these effects. The different inhibitory patterns observed may result from differences in molecular size or outer electron shell valence of the cations.

Acetylserotonin O-Methyltransferase↗
PubMed1987

Hydroxyindole-O-methyltransferase catalyses production of methoxyindoles in rat pineal gland dependent on the concentration of hydroxy precursors and their affinity for the enzyme.

Indole metabolites were separated by thin-layer chromatography following organ culture of rat pineal glands with tritiated tryptophan. Methoxyindole production was shown to differ substantially from results obtained when pineal glands were incubated with radiolabelled serotonin. The correlation between hydroxy- and corresponding methoxyindoles was, however, remarkably similar to previous results, and indicated that in the pineal gland, it is probable that production of methoxyindoles is dependent on the concentration of the various hydroxyindoles and their relative affinities for hydroxyindole-O-methyltransferase. It is also probable that although several forms of the enzyme may exist in the pineal gland, the catalytic sites are homogeneous in their activity.

5-Hydroxytryptophan↗
PubMed1986

Effect of anticonvulsant drugs in vivo on rat pineal N-acetyltransferase (EC 2.3.1.5) and hydroxyindole-O-methyltransferase (EC 2.1.1.4).

The effect of anticonvulsant drugs on daytime and nighttime N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) levels was investigated. Some of the drugs caused a significant reduction in daytime NAT and HIOMT levels, possibly owing to beta-receptor blockade although other mechanisms cannot be excluded. Sulthiame caused an increase in daytime NAT levels, and this may represent a compensatory mechanism by the pineal gland to allow normal melatonin production. None of the drugs affected nocturnal HIOMT levels, and only phenobarbitone affected NAT levels, apparently causing a shift in the nocturnal peak later in the dark phase.

Acetylserotonin O-Methyltransferase↗
PubMed1986

Methoxyindole production by the pineal gland appears to be dependent on the concentration of hydroxy precursors and their affinity for hydroxyindole-O-methyltransferase.

Various pineal gland indole metabolites were separated by thin-layer chromatography after organ culture with tritiated serotonin. The amounts of methoxyindoles produced were remarkably constant and female rats in oestrus appeared to produce greater amounts than male rats. The results show a correlation between methylation and the concentration and affinity of the various hydroxyindoles for hydroxyindole-O-methyltransferase.

Acetylserotonin O-Methyltransferase↗