Biomedical subjects

D C Rees

Publications and source records attributed to D C Rees.

169 records · Page 10Linked to original sources

PubMedDate not supplied

Effects of carbon monoxide in combination with behaviorally active drugs on fixed-ratio performance in the mouse.

The effects of carbon monoxide (3.75, 7.5, 15 and 30 ml/kg, IP) alone and in combination with ethanol (1.1 g/kg), nicotine (1.1 mg/kg), caffeine (36.1 mg/kg), chlorpromazine (2.2 mg/kg), diazepam (10 mg/kg), pentobarbital (23.1 mg/kg), d-amphetamine (1.4 mg/kg) or morphine (13.3 mg/kg) were evaluated in mice. Animals were trained to lever press under a fixed-ratio 32 schedule of water reinforcement. Response rates following CO-drug combinations were compared with the expected additive effects determined by the sum of the effects of each agent administered alone. CO (15 and 30 ml/kg) in combination with ethanol produced supra-additive effects. CO-chlorpromazine and CO-d-amphetamine combinations often produced greater than additive response-rate suppression, although differences from additivity did not reach statistical significance. The effects on response rates following CO in combination with nicotine, caffeine, diazepam, pentobarbital, or morphine were additive. These results suggest that concurrent use of therapeutic or abused drugs and CO exposure may place an individual at higher risk for behavioral toxicity.

Animals↗

PubMedDate not supplied

Scientific and regulatory issues relevant to assessing risk for developmental neurotoxicity: an overview.

The effects of chemical exposure on the developing nervous system have been documented in both humans and animals for a variety of agents. However, the comparability of these effects has not been carefully evaluated to determine the predictability of animal models to adverse effects in humans. A workshop sponsored by the U.S. Environmental Protection Agency (EPA) and the National Institute on Drug Abuse was held on April 11-13, 1989, to address the Qualitative and Quantitative Comparability of Human and Animal Developmental Neurotoxicity. Invited experts were asked to review the human and animal data on several agents that are known to cause developmental neurotoxicity in humans, including lead, methylmercury, selected abused agents, anticonvulsants, polychlorinated biphenyls (PCBs), ethanol and X-irradiation, and to make quantitative comparisons on a specific end point basis as well as on a functional category basis. In addition, they were asked to make quantitative comparisons when adequate dose-effect data were available. The data also were evaluated in the context of the proposed EPA developmental neurotoxicity testing battery to determine whether or not the battery would adequately detect the effects of each agent. Finally, four work groups were asked to reach consensus on issues relating to: 1) comparability of end points across species for developmental neurotoxicity; 2) testing methods in developmental neurotoxicity for use in human risk assessment; 3) weight-of-evidence and quantitative evaluation of data from developmental neurotoxicity studies; and 4) triggers for developmental neurotoxicity testing.

Animals↗

PubMedDate not supplied

Workshop on the qualitative and quantitative comparability of human and animal developmental neurotoxicity: summary and implications.

The Workshop on the Qualitative and Quantitative Comparability of Human and Animal Developmental Neurotoxicity was convened by the U.S. Environmental Protection Agency (EPA) and the National Institute on Drug Abuse to address issues related to when testing should be required, what test methodologies should be required, and how the data should be interpreted and applied to the risk assessment process. The background material for Work Group discussions included presentations made at the Workshop by invited experts summarizing qualitative and quantitative human and experimental animal data on specific chemicals or classes of chemicals and EPA's proposed developmental neurotoxicity testing protocol. This overview: 1) summarizes the qualitative comparisons presented at the Workshop and attempts to make some quantitative comparisons of findings across mammalian species following exposure to developmental neurotoxicants, 2) brings the common themes that were discussed among the Work Groups together into a regulatory perspective, 3) provides a status report on EPA's developmental neurotoxicity protocol, and 4) identifies research needs in the development of test methodologies and improvement of risk assessments for developmental neurotoxicants.

Animals↗

PubMedDate not supplied

Discriminative stimulus properties of toluene in the rat.

Rats were trained to discriminate toluene (100 mg/kg, IP) from vehicle in a two-lever operant task. Acquisition of the discrimination required a range of 85-219 training days. Injections of either methohexital (0.5-10 mg/kg) or oxazepam (0.5-20 mg/kg) produced toluene-lever responding in a dose-dependent fashion in most animals. The discriminative stimulus properties of toluene were not found to generalize to chlorpromazine (0.3-10 mg/kg). These results are consistent with those obtained in the mouse and provide further evidence that toluene has stimulus properties similar to those of CNS depressant drugs. These results further suggest that toluene may have drug abuse potential of the CNS depressant type.

Animals↗

PubMedDate not supplied

Solid phase synthesis of tertiary amines on amide REM resins: Grignard and metal hydride compatible resins.

Four new amide REM resins (AM REM 2-5) are described, and their use is illustrated for the synthesis of tertiary amines 6-9 and 13-16. Amide REM resins 4 and 5, which have a phenyl ring attached to the amide nitrogen, are found to give superior product yields and purities, and the resins are stable to a wider range of reagents and conditions compared to REM resin 1.

Amides↗

PubMedDate not supplied

Hemoglobin F and hemoglobin E/beta-thalassemia.

Hemoglobin (Hb) F levels are high and variable in Hb E/beta-thalassemia, ranging from 10% to 80%. The high levels are secondary to expansion of the erythron with ineffective erythropoiesis and selection in favor of cells able to make more gamma-globin. The variability in levels reflects the complex processes involved in Hb F production. Important determinants include age, alpha-thalassemia, and genetic determinants of gamma-chain synthesis. Overall, percentage of Hb F correlates with total hemoglobin levels and decreases steadily with age. alpha-thalassemia is associated with a lower percentage of Hb F levels but a higher total hemoglobin level in Hb E/beta-thalassemia.

Adult↗

PubMedDate not supplied

Acute effects of some volatile nitrites on motor performance and lethality in mice.

Mice were examined for effects on lethality and motor performance on an inverted screen test following inhalation exposure to isoamyl, n-butyl and isobutyl nitrite. All three nitrites produced concentration-related effects on both measures, with EC50s for motor performance only about one-half of the LC50s for lethality. Isoamyl and isobutyl nitrite were equally potent on both lethality and motor performance measures, whereas n-butyl nitrite was significantly more potent than isoamyl and isobutyl for lethality. Slope estimates of the concentration-effect curves for lethality were significantly greater than those of the motor performance measure. The steepness of the concentration-effect curves and low LC50/EC50 ratios relative to abused organic solvents suggest that behaviorally active concentrations of volatile nitrites may put users at risk to other health consequences.

Aerosols↗