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D J Padwick

Publications and source records attributed to D J Padwick.

5 recordsLinked to original sources

Human nocturnal blood melatonin and liver acetylation status.

The human dark phase melatonin concentrations exhibit a wide range of values. In an attempt to explain this variation, we measured 2250-2305 h melatonin levels by radioimmune assay in eleven fast and eleven slow acetylator phenotypes. No statistical difference between the two groups existed, suggesting therefore that such variations are not due to acetylator status. The study revealed a negative relationship between body weight or area and nocturnal melatonin concentration. No correlation was found between dark phase melatonin levels and age, anxiety, depression, or sleep rating.

Acetylation

Diurnal variation and melatonin induction of hepatic molybdenum hydroxylase activity in the guinea-pig.

The activities of the xenobiotic metabolizing enzymes, aldehyde oxidase and xanthine oxidase, were determined in partially purified fractions of adult guinea-pig liver at given times in the day or night. A marked circadian variation in aldehyde oxidase activity was observed with several substrates (phthalazine, phenanthridine, N-phenylquinolinium and 3,4-dihydro-4-hydroxy-3-methyl-2-quinazolinone). The main peak occurred at 0300 hr with minimum activity from 1200 to 1800 hr, the differences between rhythmic extremes being statistically significant (P less than 0.005). Xanthine oxidase activity also exhibited a daily rhythm but with a lower amplitude. Guinea-pig serum melatonin showed a synchronous circadian fluctuation with peak values at 0300 hr falling throughout the day to a minimum at 1800 hr. Exogenously administered melatonin caused a significant increase in aldehyde oxidase activity at 0900 and 1200 hr and in xanthine oxidase activity at 0900 hr. It was concluded that melatonin concentrations may be related to the circadian variation in liver molybdenum hydroxylase activity.

Aldehyde Oxidase

Effect of ibuprofen and indomethacin on human plasma melatonin.

Ibuprofen reduced human plasma melatonin (MT) after 2 h when administered orally (400 mg) at 2400 h. Increasing plasma concentrations correlated well with increasing inhibition of serum MT levels during this time. Maximum plasma ibuprofen coincided with minimum plasma MT in 3 out of 4 volunteers. Although two volunteers exhibited a partial recovery in MT levels, concentrations after 6 h were significantly less than 0600 h values in drug-free volunteers. Administration of ibuprofen (400 mg) at 1800 h delayed the nocturnal surge of plasma MT. When a slow release preparation of indomethacin (75 mg) was administered at 1800 h, the dark phase rise of plasma MT was completely prevented. Thus the longer acting cyclooxygenase inhibitor exhibited a longer lasting inhibition of plasma MT concentration.

Adult

Human post-mortem pineal enzyme activity.

The synthetic enzymes for melatonin production, serotonin-N-acetyltransferase (SNAT) and hydroxy-indole-O-methyltransferase (HIOMT) were measured in post-mortem pineal organs from eighty-eight men and women. The activity of each enzyme was correlated with age and sex. No difference was seen in either parameter when the maximum or minimum activities were measured in the death time periods of the diurnal rhythm established earlier. However, an annual bimodal rhythm was seen in HIOMT activity with maximal values occurring in January and July and minimum activities in March and October. The SNAT and HIOMT enzymes have previously been shown to be stable when measured in pineal organs held under the usual post-mortem conditions. Pineal HIOMT has also been measured in twenty-one psychotic individuals. Whilst the schizophrenic group showed significantly increased values, the schizophrenic-like group had normal values. The results were not affected by ante-mortem or post-mortem states or by drug treatment. Any clinical interpretation of pineal dysfunction in disease states need not, therefore, take into consideration age, or possible sex, but should be aware of the normal diurnal rhythm as well as the bimodal annual rhythm.

Acetylserotonin O-Methyltransferase