Biomedical subjects

P N Trennery

Publications and source records attributed to P N Trennery.

5 recordsLinked to original sources

PubMed1990

Screening procedure for assessment of ototoxicity in the common marmoset.

Detection of drug-induced ototoxicity in safety evaluation studies of novel chemical entities is rarely attempted. Where such examinations are included, they usually rely on reflex testing. The Brainstem Auditory Evoked Response can be measured with the use of externally positioned electrodes, and it monitors electrophysiologic responses to sound from the cochlear nerve and associated structures of the 8th cranial nerve. These responses have been reproducibly measured in sedated marmosets and the method shown to be a sensitive detector of hearing loss caused by loop diuretics or aminoglycoside antibiotics. additionally, where hearing damage is reversible, recovery can also be monitored. It is proposed that where a sensitive marker for ototoxicity is considered necessary as part of a multifaceted study investigating in vivo drug safety, this procedure may prove advantageous over existing methods.

Animals↗

PubMed1987

Local myotoxicity of ketamine hydrochloride in the marmoset.

An investigation of raised plasma aspartate aminotransferase (AST) in marmosets after intramuscular ketamine injection suggested a local myotoxicity. This was confirmed by a range of histopathological findings from myofibrillar striation loss to necrosis. In addition to the elevations in AST levels, creatine kinase and the lactate dehydrogenase-5 isoenzyme levels were elevated. It was further demonstrated that, although the physical properties of the injectable solution (pH, osmolality) and to a lesser extent the injection procedure itself caused slight changes in plasma enzyme levels, the ketamine was predominantly responsible for the lesion. No hepatic interactions were seen. This effect should be taken into consideration when this anaesthetic is used in the marmoset if the primary objectives of the experiment entail routine blood analyses.

Animals↗

PubMed1985

The influence of an experimental liver cirrhosis upon the metabolism of diazepam and imipramine hydrochloride in the rat.

When either diazepam or imipramine hydrochloride was administered orally to rats with thioacetamide-induced hepatic cirrhosis, the biliary and faecal elimination of metabolites was significantly decreased compared with that in normal animals. However, renal excretion of metabolites of diazepam or imipramine was increased in the liver-damaged rats. Experiments in vitro showed that liver homogenates from cirrhotic rats metabolized diazepam or imipramine hydrochloride in qualitatively and quantitatively similar ways to those from normal rats. Clearance of radioactivity from the blood following i.v. administration of either diazepam or imipramine hydrochloride was prolonged in animals with experimental cirrhosis.

Animals↗

PubMed1983

Early changes in thioacetamide-induced liver damage.

Plasma amino acids, serum enzymes, liver glutathione and the hepatic lipid peroxidation capacity of the rat were investigated in acute thioacetamide toxicity. These were examined in parallel with the earliest pathological changes shown by electron microscopy. Plasma arginine levels were significantly lowered 3 h after dosing thioacetamide and by 9 h were indistinguishable. This finding correlates with other workers demonstrating urea cycle damage in alcohol and carbon tetrachloride damaged rat liver. Depressed arginine plasma levels were detectable before any of the biochemical or pathological processes co-examined and as such may prove useful as a sensitive in vivo method for detection of acute liver damage.

Acetamides↗

PubMed1983

The metabolism of thioacetanilide in the rat.

The metabolism and acute toxicity of thioacetanilide was studied in the rat. Following intragastric dosage (100 mg/kg), over 90% dose was excreted in urine, predominantly as conjugated metabolites: less than 7% was recovered in the faeces, consisting of unchanged thioacetanilide. N-Acetyl-4-aminophenol sulphate was the major urinary metabolite, with smaller amounts of conjugated 4-hydroxythioacetanilide and unmetabolized thioacetanilide. Biliary excretion amounted to only 3.4% and was N-acetyl-4-aminophenol glucuronide. Although desulphuration was a major metabolic pathway in the rat, no hepatic toxicity (shown by serum enzymes, plasma bilirubin, hepatic glutathione and cytochrome P-450 levels) occurred up to doses of 500 mg/kg. Combination of rapid 4-hydroxylation, absence of sulphoxide formation, and the structural tautomerism exhibited by thioacetanilide may be, in part, responsible for these findings.

Acetanilides↗