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Biomedical subjects

D Couri

Publications and source records attributed to D Couri.

At least 55 records · Page 3Linked to original sources
PubMed1979

The pharmacodynamics of 4-(p-chlorophenylthio)butanol (W-2719) in humans.

4-(p-Chlorophenylthio)butanol (W-2719) is absorbed, metabolized and excreted when administered orally to human volunteers. The butyrate (W-2718) and the acetate (W-2683) metabolites were found in plasma with W-2683 being the major biotransformation product and detectable seven days after administration with an apparent half-life of 33.2 h. p-Chlorothiophenol appeared to be the major biotransformation product in urine and was detectable through day 6. As in plasma, the other major biotransformation product was W-2683, which was again detectable through day 7 and had a t 1/2 in urine of 40.8 h. The minor metabolite found in urine was W-2718. No W-2719 was found in either plasma or urine after oral administration.

Adult↗
PubMed1978

The effect of 2-hexanone and 2-hexanone metabolites on pupillomotor activity and growth.

Neurotoxic agents such as MBK (2-hexanone) and MBK metabolites were fed in drinking water to guinea pigs. Effects of these solvents on locomotor activity were studied. Dynamic pupillometry indicated that MBK, 2,5-hexanedione and 2-hexanol decreased pupillary response throughout the first five weeks; by the 24th week, all treatment groups showed a greatly impaired pupillary response. From biotransformation studies, it is possible that the 2-hexanol effect on pupillary response may be attributed to its conversion to MBK and/or 2,5-hexanedione. Each of the solvents increased body weight, but decreased locomotor activity. The pupillary changes reported here may serve as an index of solvent exposure in the work environment, if such measurements were to be conducted on workers.

Animals↗
PubMed1978

Biotransformation of n-hexane and methyl n-butyl ketone in guinea pigs and mice.

Peripheral neuropathies caused by exposures to the industrial solvents n-hexane and MBK exhibit strinkingly similar characteristics. In in vivo studies, the metabolites of MBK and n-hexane identified in blood and urine of guinea pigs were 2-hexanol (partly as glucuronide in urine); and 2,5-hexanedione which was detected only in MBK treated groups. Phenobarbital pretreatment increased 2-hexanol urinary excretion in both solvent treatment groups. In in vitro studies, hepatic reduction of MBK required the cytosol fraction to form 2-hexanol; whereas the oxidation of MBK and n-hexane required the microsomal fraction to form 2,5-hexanedione and 2-hexanol, respectively. The in vivo and in vitro biotransformation of MBK and n-hexane to a common metabolite (2-hexanol) suggests that the neurotoxic action of these solvents may be metabolite related.

Animals↗
PubMed1978

Polyneuropathy from inhalation of N2O cartridges through a whipped-cream dispenser.

A generalized toxic polyneuropathy was identified in a 23-year-old woman after excessive intentional inhalation of compressed N2O delivery from cartridges through a whipped-cream dispenser. The chronology of the patient's N2O abuse correlated clearly with two episodes of recurrent polyneuropathy. The toxic effects were limited to the nervous system, primarily involving the peripheral nerves, although some signs suggested a possible effect on the cerebellum or its connections. The findings on sural nerve biopsy were nonspecific, characterized principally by axonal degeneration. Gas chromatographic analysis of the N2O cartridges dispensed through the whipped-cream canister revealed an exposure to N2O and 26 other compounds. Three of these, trichloroethylene, toluene, and phenol, are known neurotoxins.

Adult↗
PubMed1978

The effects of different levels of selenium administered to rats in drinking water on distribution and glutathione peroxidase.

Studies were conducted in an attempt to define a biochemical index of selenium toxicity rather than weight loss, liver disease and death. Rats, maintained on selenium deficient diets, received in drinking water various levels of selenium as Na2SeO3(0.1, 1.0, 1.5, 2.0 ppm). Changes in selenium dependent glutathione peroxidase (GSH-Px) activities and specific activities (nCi75Se/ug Se) were determined in liver, kidney and plasma at baseline and two and ten weeks after repletion. In intial selenium deficient rats, GSH-Px activities were markedly depressed and specific activities elevated as compared to 0.1 ppm controls. After two weeks, liver and plasma GSH-Px activiities increased, and plasma, liver and kidney specific activities decreased in a concentration dependent manner. In kidney, there were no differences in enzyme activity at either two or ten weeks. At ten weeks, liver GSH-Px activities continued to increase in the 1.0 ppm group, but were depressed at both the 1.5 and 2.0 ppm levels. Specific activities were also depressed in liver and excretion was not increased at these levels. This suggests a biochemical toxicity in liver at levels above 1.0 ppm after ten weeks, prior to the onset of gross pathological changes.

Animals↗
PubMed1977

Alterations of fast axoplasmic transport in experimental methyl n-butyl ketone neuropathy.

Methyl n-butyl ketone (MBK) is known to produce a giant axonal neuropathy in man and experimental animals characterized pathologically by a gradual increase in the number of neurofilaments which become associated with focal areas of axonal swelling and thinning of the myelin sheath. Fast axoplasmic transport was studied in rats exposed to MBK. In 10 severely paralyzed rats exposed to MBK there was a significant impediment of fast axoplasmic transport following dorsal root ganglion injections (x +/- S.D. = 283.2 +/- 20.34 mm/day) compared to normal controls (417.6 +/- 23.78 mm/day). In rats undergoing injections into the ventral horn of the spinal cord there was a gradual impairment of the mean down flow rate for transport of [3H]leucine which correlated with the severity of the MBK induced neuropathy. Quantitative morphological determinations showed that the total number of neurotubules per unit cross-sectional myelin area and the number of neurotubules associated with mitochondria in swollen axons was unchanged from normal. The total number of mitochondria in randomly sampled axons varied significantly from controls but the absolute number of mitochondria associated with neurotubules was unchanged from normal. The results of these studies suggest that the impediment of fast axoplasmic transport may be related to the increased neurofilaments producing focal areas of axonal blockage.

Animals↗
PubMed1976

Toxicity and metabolism of methyl n-butyl ketone.

MEK (2-butanone) when combined with MBK (2-hexanone) markedly enhanced MBK neurotoxicity. MBK in rat plasma after exposure to MBK/MEK increased with time. Metabolites of MBK identified in blood and urine of rats and guinea pigs were 2-hexanol and 2,5-hexanedione.

Animals↗
PubMed1974

Toxic polyneuropathy produced by methyl N-butyl ketone.

A polyneuropathy affecting a large number of workers was recently observed at a plant producing plastic-coated and color-printed fabrics. Epidemiological data suggested strongly that methyl N-butyl ketone (MBK) was responsible for the outbreak. This hypothesis is now supported by the development of a peripheral neuropathy in chickens, rats, and cats exposed to MBK at atmospheric concentrations of 200 to 600 parts per million, 24 hours per day, 7 days per week. Although the animals were exposed continuously and the affected workers were exposed intermittently, the averages of the total number of hours of exposure for development of the peripheral neutropathy in the animals and workers were remarkably close.

Animals↗