Inter-strain variability in aldehyde oxidase activity in the mouse.

Aldehyde oxidase (AO) is a cytosolic enzyme expressed predominantly in the liver. AO is involved in the metabolism of many xenobiotics of pharmacological and toxicological importance including antivirals (famciclovir), antimalarials (quinine) and anticancer drugs (5-fluoro-2-pyrimidine and methotrexate). The aim of this study was to characterize AO activity in different strains of mice using two different substrates. AO activity in the cytosolic fraction was characterized using the metabolism of N-[2-(dimethylamino)ethyl]acridine-4-carboxamide (DACA), a novel antitumor drug, to form DACA-9(10H)-acridone (quantified by HPLC with fluorescence detection) and benzaldehyde to form benzoic acid (quantified spectrophotometrically). Characterization of mouse AO activity with DACA showed 15-fold variation in K(m), 10-fold variation in apparent V(max) and twofold differences in intrinsic clearance. Nude mice and C129/C57 had the highest intrinsic clearance (0.66 and 0.l53 ml/min per mg protein, respectively). Nude mice cleared DACA faster than nude tumor bearing mice by a factor of 2. Male Swiss CD had higher intrinsic clearance than female Swiss CD (0.36 and 0.28 ml/min per mg protein). A similar pattern of enzyme activity was observed with benzaldehyde; however, the extent of variation was less than that found with DACA. In conclusion, our results show that there are both strain and gender differences in AO activity. These differences are better detected by DACA. Furthermore, these results suggest caution when extrapolating the data obtained from mouse AO studies to humans.

Individual variation in hepatic aldehyde oxidase activity.

Aldehyde oxidase (AO) is a molybdo-flavo enzyme expressed predominantly in the liver, lung, and kidney. AO plays a major role in oxidation of aldehydes, as well as oxidation of various N-heterocyclic compounds of pharmacological and toxicological importance including antiviral (famciclovir), antimalarial (quinine), antitumour (methotrexate), and nicotine. The aim of this study was to investigate cytosolic aldehyde oxidase activity in human liver. Cytosolic AO was characterised using both the metabolism of N-[(2-dimethylamino)ethyl] acridine-4-carboxamide (DACA) and benzaldehyde to form DACA-9(10H)-acridone (quantified by HPLC with fluorescence detection) and benzoic acid (quantified spectrophotometrically). Thirteen livers (10 female, 3 male) were examined. The intrinsic clearance (Vmax/Km) of DACA varied 18-fold (0.03-0.50 m/min/mg). Vmax ranged from 0.20-3.10 nmol/ min/mg, and Km ranged from 3.5-14.2 microM. In the same specimens, the intrinsic clearance for benzaldehyde varied 5-fold (0.40-1.8 ml/min/mg). Vmax ranged from 3.60-12.6 nmol/min/mg and Km ranged from 3.6-14.6 microM. Furthermore, there were no differences in AO activity between male and female human livers, nor was there any relationship to age of donor (range 29-73 years), smoking status, or disease status. In conclusion, our results showed that there are variations in AO activity in human liver. These variations in aldehyde oxidase activity might reflect individual variations or they might be due to AO stability during processing and storage.

Long-term effects of nitrous oxide anaesthesia on laboratory and clinical parameters in elderly Omani patients: a randomized double-blind study.

AIMS: This study examined the long-term effects of nitrous oxide anaesthesia on serum levels of cobalamin and folate, red cell folate levels and haematological parameters, and neurological status in elderly Omani patients. METHODS: Sixty-nine consecutive patients undergoing ophthalmic surgery were randomly and double-blind assigned to nitrous oxide or propofol anaesthesia. They met the following entry criteria: age 55 years or above, no major organ failure, no clinical signs or symptoms of cobalamin or folate deficiency, mean cell volume (MCV)

Peripheral polyneuropathy due to chronic use of topical ammoniated mercury.

BACKGROUND: Despite their potentially disastrous side effects, topical mercury salts can still be found as ingredients in some over-the-counter preparations or local remedies. CASE REPORT: Peripheral polyneuropathy as a result of chronic ammoniated mercury poisoning was studied and followed over 2 years. A 36-year-old man developed peripheral polyneuropathy following chronic perianal use of an ammoniated mercury ointment. Highly elevated blood and urine mercury levels were found. Sural nerve biopsy showed mixed axonal degeneration-demyelination. There was progressive improvement of his symptoms over 2 years but neurophysiological examination revealed incomplete recovery. CONCLUSION: The availability of safer drugs should result in a complete ban of these dangerous compounds.