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Biomedical subjects

J E Bright

Publications and source records attributed to J E Bright.

30 records · Page 2Linked to original sources

Kinetics of methaemoglobin production. (2). Kinetics of the cyanide antidote p-aminopropiophenone during oral administration.

The kinetics of methaemoglobin production by orally administered p-aminopropiophenone (PAPP) was studied by using a kinetic model previously developed to describe methaemoglobinaemia consequent on intravenous injection of PAPP. Both ISIS, a simulation package, and NONLIN, a non-linear least-squares regression analysis program, were used to analyse the data. Some modification of the model was necessary to describe oral profiles and 40-50% of the administered PAPP appeared to be being metabolized at first pass to a non-active metabolite.

Administration, Oral↗

The induction of methaemoglobin by p-aminophenones.

Four aminophenones were administered to dogs. Orally p-aminopropiophenone (PAPP) was the most effective methaemoglobin former, while p-aminoheptanoylphenone (PAHpP) was the least effective. p-Aminovalerylphenone (PAVP) and p-aminohexanoylphenone (PAHP) were of intermediate efficacy. With oral PAPP, PAVP and PAHP there was no clear cut relationship between acyl chain length and the timing of peak mean methaemoglobin levels. When PAPP or PAHP were administered intravenously the latter produced lower and later peak methaemoglobin levels than the former.

Animals↗

A model for the induction of moderate levels of methaemoglobinaemia in man using 4-dimethylaminophenol.

The induction of moderate levels of methaemoglobin by 4-dimethylaminophenol (DMAP) was studied in human and dog blood in vitro and in dogs in vivo. Although the rate of formation of methaemoglobin following intravenous injection into dogs was similar to that following addition of DMAP to dog blood in vitro, in the latter case levels fell more slowly. Addition of DMAP at the same concentrations in vitro resulted in more rapid oxidation of haemoglobin and higher peak levels of methaemoglobin in dog blood than in human blood. It was concluded that the rate of formation of methaemoglobin as well as the activity of methaemoglobin reductase must be considered when extrapolating data from the dog to man.

Aminophenols↗

Acute oral toxicity of 4-dimethylaminophenol to the gastrointestinal tract, liver and kidney of the rat.

Single oral doses up to 25 mg/kg body weight of methaemoglobin-inducing cyanide antidote, 4-dimethylaminophenol (DMAP) did not result in any gross or histological abnormality in the gastrointestinal tract, liver and kidneys of rats killed up to 24 h after the dose. In animals kept for 7 days after the dose to abnormality was observed in the organs examined or in blood samples taken during the course of the experiment.

Aminophenols↗

Comparison of kinetic and end-point microdensitometry for the direct quantitative histochemical assessment of cytochrome oxidase activity.

Cytochrome oxidase activity has been assessed by a method of kinetic microdensitometry which involves applying tissue sections to gel films containing phenylamine substrates and measuring the rate of azine dye production by continuously recording the rate of change in extinction. Optimum conditions for the technique were defined, and the results compared with those obtained by conventional end-point microdensitometry in which sections are incubated in histochemical substrate solutions and azine dye production estimated by a single measurement of extinction at the end of the incubation period. When compared with biochemically-determined enzyme activity, kinetic microdensitometry gave a better index of the proportionate activity of cytochrome oxidase in various normal tissues than did end-point microdensitometry. In addition, the degree of inhibition of cytochrome oxidase activity in tissues removed from cyanide-poisoned animals was assessed more reliably by kinetic microdensitometry than by end-point measurements. With end-point microdensitometry, the reaction is non-linear over the comparatively long incubation times required and there is also a spontaneous reactivation of cyanide-inhibited cytochrome oxidase during incubation and thus a progressively increased rate of substrate utilization. In contrast, with kinetic microdensitometry the initial linear reaction rate is measured before significant reactivation occurs. Kinetic microdensitometry can be used for direct dynamic quantitation of enzyme activity in tissues or cells; it may be a valuable technique for quantitative histochemical confirmation or extension of biochemical studies; and it appears to be a reliable direct quantitative histochemical method for investigating in vivo inhibition of enzyme activity, where spontaneous reactivation of the enzyme-inhibitor complex may occur.

Animals↗