Moderate drinking and health. Implications of recent evidence.

Objective: To address three questions (Is moderate drinking good for health? Should people drink to prevent heart disease? What is moderate drinking?) and to examine and compare two recent Canadian guidelines on low-risk drinking in the context of counseling patients.

Data Sources: English-language data sources were searched, particularly peer-reviewed health and social science literature and recent expert reports.

Study Selection: Studies and reports were selected for their scientific merit and direct relevance to the three questions addressed and to the formulation of guidelines on low-risk drinking.

Overview of studies on drinking patterns and consequences.

Research on selected consequences of alcohol use are reviewed in terms of how alcohol use is measured and reported in research designs common to that area of study. In addition, evidence of the probable underlying mechanisms by which alcohol leads to the various consequences is examined, particularly in relation to the aspects of drinking pattern which are theoretically most relevant to the outcome. There is considerable variation in the degree to which research in these areas stresses pattern of drinking (as opposed to average amount consumed or total dose).

On the emerging paradigm of drinking patterns and their social and health consequences.

Recent epidemiological and social studies have increasingly pointed to the importance of drinking patterns in explaining consequences of alcohol consumption. This paper presents recommendations for research in the area based on the presentations and discussions of the first "International Conference on Social and Health Effects of Different Drinking Patterns" held in Toronto in November 1995. In particular, the social dimension in pattern research, and the relationship between patterns of drinking and casualties as well as social harm, are stressed.

Lead potentiates iron-induced formation of reactive oxygen species.

There are reports that lead may promote free-radical initiated events in biological tissue. However, there are also reports on the inability of lead salts to stimulate the production of reactive oxygen species in isolated systems. Furthermore, there is no well understood rationale as to why lead should exhibit pronounced pro-oxidant properties.

Prevention of ethanol-induced changes in reactive oxygen parameters by alpha-tocopherol.

Rats were given a 200 mg/kg body weight daily dose of alpha-tocopherol by i.p. injection for 15 days.

Determinants of suggestions for alcohol treatment.

Entry to treatment is often precipitated by suggestions or pressure from relatives or friends, but we know little of the circumstances in which suggestions to cut down on drinking include advice to seek professional help. In 1993, 1034 Ontario adults were asked in a random digit dialling telephone survey if they had said something to a friend or relative about their drinking, or suggested they cut down. About 35% had said something within the last year, and 15% had taken the further step of suggesting they seek professional help or helping them get assistance.

Effect of an NMDA receptor antagonist and a ganglioside GM1 derivative upon ethanol-induced modification of parameters of oxidative stress in several brain regions.

Dietary administration of ethanol to rats for 2 weeks was able to depress levels of glutathione (GSH) and Cu/Zn superoxide dismutase (SOD) in several brain regions. This was indicative of the generation of excess levels of reactive oxygen in treated animals. The potentially protective effect of both an NMDA receptor blocker (MK-801) and an internally esterified derivative of ganglioside GM1 (AGF2) upon ethanol-induced changes in these indices of oxidative stress, was studied.

Dietary α-tocopherol content modulates responses to moderate ethanol consumption.

Rats were fed with diets containing differing amounts of α-tocopherol for 21 days. For the latter 14 days of this period, one half of the rats also received ethanol (7% v/v) in the drinking water. Treatments did not alter the rate of weight gain between groups.

The promotion of iron-induced generation of reactive oxygen species in nerve tissue by aluminum.

Aluminum is suspected to play a role in several neurological disorders. Reactive oxygen species (ROS) lead to oxidative stress, which is thought to be a possible mechanism for neurological damage. Interactions between aluminum and iron, a known promoter of prooxidant events, were studied in cerebral tissues using a fluorescent probe to measure rates of generation of ROS.

Stimulation of synaptosomal free radical production by fatty acids: relation to esterification and to degree of unsaturation.

The ability of three fatty acids and their respective ethyl esters, to promote generation of reactive oxygen species (ROS), was compared in a preparation of rat brain synaptosomes. Arachidonic but not palmitic or linoleic acids promoted ROS generation. Ethyl esterification of each fatty acid significantly enhanced ROS production and also levels of lipid peroxidaton.

Excitotoxins, aging, and environmental neurotoxins: implications for understanding human neurodegenerative diseases.

We are an aging society and current demographic trends point to a likely increase in age-related neurodegenerative diseases. The aged population may have a number of unique risk factors that result in a predisposition to neuronal damage from environmental neurotoxins. This symposium addressed the involvement of excitatory amino acids as final common mediators of neuronal death associated with various types of neurotoxic insult.

The risk of harm to oneself from drinking, Canada 1989.

In a national sample of 11,634 Canadians aged 15 years and above, risk curves for harm to six life-areas from one's own drinking and for assault by another drinker rose steadily with the respondent's volume of alcohol consumption. While drinking five or more drinks on an occasion at least once a month substantially raised the risk at a given volume of drinking, the risk rose with volume even among those not regularly drinking five or more drinks. These relationships remained in logistic regressions which controlled for gender, age and educational level.

The relation of oxidative stress and hyperexcitation to neurological disease.

The expression of a considerable range of neurological diseases is thought to involve two pathological states, namely, the production of excessive amounts of reactive oxygen species and neuronal hyperactivity. These events may represent an outcome of general vulnerable features of nervous tissue. Since they are associated with many unrelated diseases, the phenomena may be considered the final common pathways of a range of metabolic defects.

Cerebral membranes isolated from rats consuming ethanol or gestationally exposed to ethanol have increased susceptibility to modulation by ethanol.

The actions of ethanol on membrane fluidity were examined. All assays were carried out using fluorescence techniques in the P2 fraction of crude synaptosomes isolated from rat brain. Subchronic treatment of rats with ethanol revealed a significant increase in order at the membrane interior.

Inhibition of plasma membrane and mitochondrial transmembrane potentials by ethanol.

The actions of ethanol and its primary oxidative metabolite, acetaldehyde, on plasma membrane and mitochondrial transmembrane potentials were examined in rat brain using fluorescence techniques. Subchronic treatment of adult rats with ethanol resulted in a significant depolarization of both the plasma and mitochondrial membranes when the mean blood ethanol level of the rats was 59 +/- 11 mM (mean +/- SEM, n = 6). Acute dosing of animals (4.

Regional selectivity in ethanol-induced pro-oxidant events within the brain.

Several biochemical parameters that reflect the presence of excess levels of reactive oxygen species were modulated in the brains of rats exposed acutely or subchronically to ethanol. These parameters included depression of cytosolic glutathione (GSH) concentration and of glutamine synthetase levels. However, using these indices, there was a significant difference in susceptibility to ethanol in different brain regions.

Changes in markers of oxidative status in brain, liver and kidney of young and aged rats following exposure to aromatic white spirit.

Levels of glutathione and activity of glutamine synthetase were assayed in organs of rats following inhalation of a heterogeneous solvent mixture containing both aliphatic and aromatic hydrocarbons. This mixture was administered for 3 weeks (6 h daily) at two levels in the inhaled air (400 and 800 ppm) to young adult (5-month-old) and aged (14-month-old) rats. Depression of levels of glutamine synthetase in the P2 fraction of kidney was observed, which was more severe in aged than young adult rats.

The effect of metal ions on free radical formation in lung and brain of rats.

The influence of 14 metal ions on free radical (FR) formation in subcellular systems of lung mitochondria and brain synaptosomes (cortex and cerebellum) of rats was investigated. Iron and manganese showed a highly significant increase in FR formation in lung, whereas other investigated metal ions showed relatively slight, insignificant decreases in FR. The significant enhancement effects of iron and manganese increased with their content in the media.

Detecting, preventing, and managing patients' alcohol problems.

Objective: To examine Canadian family physicians' attitudes, beliefs, and practices regarding alcohol use and alcohol-related problems among their patients.

Design: A self-administered questionnaire mailed to a random sample of 2883 family physicians. The survey was conducted using a modified Dillman method.

Effect of ethanol treatment on indices of cumulative oxidative stress.

The effect of ethanol exposure upon several parameters relating to oxidative stress has been examined in brain and liver. A single administration of either acetaldehyde or ethanol was able to enhance rates of generation of reactive oxygen species in liver but this effect was not apparent in the cerebral cortex. Glutamine synthetase is especially sensitive to inactivation by free radicals and evidence for cumulative oxidative damage to this enzyme was found in liver and to a lesser extent in cerebral cortex.

Contribution of hepatic cytochrome P450 systems to the generation of reactive oxygen species.

The rate of generation of reactive oxygen species (ROS) in hepatic microsomes was assayed using a fluorescent probe. This rate was stimulated in a manner proportional to the concentration of NADPH present. NADH could not be substituted for NADPH, and an inhibitor of mixed-function oxidases (SKF 525A) blocked stimulation by NADPH.

Effects of ethanol treatment upon sources of reactive oxygen species in brain and liver.

Sources of reactive oxygen species (ROS) generation have been compared in microsomal and mitochondrial fractions of brain and liver from ethanol-treated and control rats. Rates of ROS generation were quantitated with the fluorescent probe precursor, 2'7'-dihydrochloroflurescin diacetate, whose validity has been previously established. The production of active pro-oxidant species was measured in the presence of various selective inhibitors of enzymes potentially able to contribute to oxidative events.

Immunogenicity of synthetic HIV-1 gp120 V3-loop peptide-conjugate immunogens.

A successful prophylactic human immunodeficiency virus type 1 (HIV-1) vaccine must elicit an immune response that will prevent establishment of the persistent viral infection. The only response shown to be effective in this regard is virus-neutralizing antibody directed against the viral gp120 hypervariable V3-loop region. Conjugate immunogens, containing cyclic peptides representing the V3 determinant covalently bound to a carrier protein, were capable of eliciting virus-neutralizing antibodies.