Eugene C. Dinovo

Ethanol-induced conformational changes in rat brain microsomal membranes

Abstract The conformation of membrane-bound proteins was monitored by the reaction of sulfhydryl (SH) groups with N -ethyl maleimide (NEM) and 5,5′-dithiobis (2-nitrobenzoic acid) (DTNB). Brain microsomes isolated from rats chronically imbibing a 10% (v/v) ethanol solution were found to contain 12–16 per cent more DTNB-reactive SH groups than similarly isolated controls. [ 3 H]NEM reacted with 32 per cent more SH groups in the microsomes obtained from ethanol-treated rats than controls. Since no change in the protein composition was evident from disc electrophoresis, and no significant differences in the total number of SH groups was present between the two samples, these findings suggest a conformational change in the microsomal membrane. Microsomes isolated from ethanol-naive animals, when treated with ethanol in vitro , showed a dose-dependent decrease in DTNB-reactive SH groups. The results indicate that the neural membrane may exist in different morphological states during acute and chronic exposure to ethanol.

Alterations of fast-reacting sulfhydryl groups of rat brain microsomes by ethanol

Abstract Brain microsomes isolated from rats chronically imbibing 10% ethanol contained 12–16% more 5,5′-dithiobis-(2-nitrobenzoic acid) (DTNB) fast-reacting sulfhydryl (SH) groups than microsomes from control animals. (3H)N-ethylmaleimide was also shown to react with more SH groups in the microsomes of ethanol imbibing rats than the controls. No changes were found in the total SH groups or in the disc gel electrophoresis protein banding profiles between the two fractions. However, the acute exposure of microsomes from ethanol-naive animals to ethanol resulted in a dose-dependent decrease in DTNB-reactive SH groups. These findings were interpreted as arising from time-dependdent conformational changes in the membrane due to the presence of ethanol or compensatory response to such changes.

A Review of Psychoactive Drug-Involved Deaths in Nine Major United States Cities

Detailed psychosocial and biomedical data were collected in 2,000 psychoactive drug-involved deaths occurring from 1972 through 1974 in nine large cities in the United States. The cases were selected representatively by the medical examiners or coroners in each city. Also, proficiency studies were carried out of the toxicological laboratories associated with these nine cooperating data collection centers. There were striking intercity psychosocial and biomedical differences in these psychoactive drug-involved deaths. These differences were based not simply in demographic regional population differences but also on the kinds of psychoactive drugs used as well as the role of the drug in contributing to death and whether the death was a result of an accident, suicide, homicide, or unknown intent. Also, a lack of uniformity was demonstrated in the quality control of the toxicological laboratories associated with the offices of these nine medical examiners or coroners, which suggests varying degrees of accuracy in resulting medicolegal diagnoses. Hence national programs of drug abuse deterrence or prevention and treatment should deal specifically with the variety of psychoactive drug-involved deaths occurring in different urban areas rather than approaching these problems globally as if they were uniform and homogeneous, and our toxicological proficiency studies accentuate the importance of mandatory quality control studies for all toxicological laboratories in the United States.