Lymphocyte proliferation inhibitory factor (PIF) in alcoholic liver disease.
Lymphocyte proliferation inhibitory factor (PIF) was determined in the supernatants of PHA-stimulated lymphocytes from patients with alcoholic liver disease. PIF was assayed by determining inhibition of DNA synthesis in WI-38 human lung fibroblasts. A two-fold greater inhibition in thymidine incorporation into DNA by lung fibroblasts was observed in supernatants of PHA stimulated lymphocytes from patients with alcoholic hepatitis or active Laennec's cirrhosis as compared with that found in control subjects or patients with fatty liver. It is suggested that decreased liver cell regeneration seen in some patients with alcoholic hepatitis may be due to increased elaboration of PIF. (+info)
Antibodies against phospholipids and oxidized LDL in alcoholic patients.
Antiphospholipid antibodies (APA) are a generic term describing antibodies that recognize various phospholipids. Hepatocyte damage is a cardinal event in the course of alcoholic liver injury and autoantibodies against phospholipids could play an important role in this process. APA in alcoholic patients seem to reflect membrane lesions, impairment of immunological reactivity, liver disease progression and they correlate significantly with disease severity. LDL oxidation is supposed to be one of the most important pathogenic mechanisms of atherosclerosis and antibodies against oxidized low-density lipoprotein (oxLDL) are some kind of an epiphenomenon of this process. The scope of our study was to determine some autoantibodies (IgG-oxLDL and antiphospholipid antibodies) and their possible changes in alcoholic patients. We studied IgG-oxLDL and four APA - anticardiolipin antibodies (ACA), antiphosphatidylserine antibodies (APSA) antiphosphatidylethanolamine antibodies (APE) and antiphosphatidylcholine antibodies (APCA) in 35 alcoholic patients with mildly affected liver function at the beginning of the abuse treatment. The control group consisted of 60 healthy blood donors. In the studied group, we obtained positive results concerning total ACA in 17.1 % of alcoholic patients (8.3 % in the control group), 11.4 % IgG-ACA (6.7 %), 8.6 % IgM-ACA (3.3 %), 14.3 % total APE (6.7 %), 14.3 % total APCA (8.3 %) and 20 % total APSA (8.3 % in the control group). The IgG-oxLDL (406.4+/-52.5 vs 499.9+/-52.5 mU/ml) was not affected in alcoholic patients. We conclude that the autoantibodies against oxLDL are present in sera of alcoholics and healthy blood donors. Based on our results which revealed a wide range of IgG-oxLDL titres in the healthy population, this parameter does not appear to be very promising for the evaluation of the risk of atherosclerosis. Alcoholics with only mild affection of liver functions did not exhibit a significantly higher prevalence of all studied antiphospholipid antibodies (ACA, APSA, APE, APCA) which could lead to membrane lesions in these patients. (+info)
Involvement of cytochromes P-450 2E1 and 3A4 in the 5-hydroxylation of salicylate in humans.
Hydroxylation of salicylate into 2,3 and 2,5-dihydroxybenzoic acids (2,3-DHBA and 2,5-DHBA) by human liver microsomal preparations was investigated. Kinetic studies demonstrated that salicylate was 5-hydroxylated with two apparent Km: one high-affinity Km of 606 microM and one low-affinity Km greater than 2 mM. Liver microsomes prepared from 15 human samples catalyzed the formation of 2,5-DHBA at metabolic rate of 21.7 +/- 8.5 pmol/mg/min. The formation of 2, 3-DHBA was not P-450 dependent. Formation of 2,5-DHBA was inhibited by 36 +/- 14% following preincubation of microsomes with diethyldithiocarbamate, a mechanism-based selective inhibitor of P-450 2E1. Furthermore, the efficiency of inhibition was significantly correlated with four catalytic activities specific to P-450 2E1, whereas the residual activity was correlated with three P-450 3A4 catalytic activities. Troleandomycin, a mechanism-based inhibitor selective to P-450 3A4, inhibited by 30 +/- 12% the 5-hydroxylation of salicylate, and this inhibition was significantly correlated with nifedipine oxidation, specific to P-450 3A4. The capability of seven recombinant human P-450s to hydroxylate salicylate demonstrated that P-450 2E1 and 3A4 contributed to 2, 5-DHBA formation in approximately equal proportions. The Km values of recombinant P-450 2E1 and 3A4, 280 and 513 microM, respectively, are in the same range as the high-affinity Km measured with human liver microsomes. The plasmatic metabolic ratio 2,5-DHBA/salicylate, measured 2 h after ingestion of 1 g acetylsalicylate, was increased 3-fold in 12 alcoholic patients at the beginning of their withdrawal period versus 15 control subjects. These results confirm that P-450 2E1, inducible by ethanol, is involved in the 5-hydroxylation of salicylate in humans. Furthermore, this ratio was still increased by 2-fold 1 week after ethanol withdrawal. This finding suggests that P-450 3A4, known to be also inducible by alcoholic beverages, plays an important role in this increase, because P-450 2E1 returned to normal levels in less than 3 days after ethanol withdrawal. Finally, in vivo and in vitro data demonstrated that P-450 2E1 and P-450 3A4, both inducible by alcohols, catalyzed the 5-hydroxylation of salicylate. (+info)
The role of gamma-hydroxybutyric acid in the treatment of alcoholism: from animal to clinical studies.
Since its discovery nearly 40 years ago, gamma-hydroxybutyric acid (GHB) has attracted several waves of scientific interest due to new developments in the knowledge of its mechanisms of action and ideas for its potential use in clinical practice. Its effects have been claimed to treat different psychiatric conditions, but over time its use has become limited to a few specific situations (e.g. sedating patients in non-painful surgical procedures and narcolepsy). New interest in the drug derives from its potential use in the treatment of alcoholism. Recent studies demonstrated a marked effect of the substance in suppressing ethanol (ETOH) withdrawal symptoms and in reducing craving for alcohol, compared to other available drugs. However, GHB has to be given under very careful supervision because of its side-effects, including the risk of abuse and dependence and possible interference with the metabolic pathways of endogenous GHB and ETOH. This short review discusses these and related issues and we hope that it will stimulate further interest in GHB. (+info)
The impact of Alcohol and Alcoholism among substance abuse journals.
This article concerns the question of journal impact factor and other bibliometric indicators made available by the Institute for Scientific Information in their Journal Citation Report for 1996. The impact factors of journals within the subject category 'substance abuse' are listed along with total citations, immediacy indices, and cited half-lives. The relationship between cited and citing journals is discussed with the main focus on the data available for Alcohol and Alcoholism. Some of the problems and limitations of bibliometric measures of productivity are dealt with, especially when these are used to evaluate the work of individual scientists. Although bibliometric measures are easy to compute, they become difficult to interpret, such as when dealing with collaborative research and the problem posed by multiple authorship. The need to adjust impact factors and citation counts for the number of co-authors in a paper becomes important when credit has to be attributed to one individual from a multi-author paper. This is often necessary in connection with grant applications and when making decisions about academic promotion and tenure. The impact factor of Alcohol and Alcoholism has increased steadily over the past 5 years, even after adjusting for the number of self-citations, which resulted in an even greater increase in impact. However, the impact factors of substance abuse journals are generally low, compared with disciplines such as immunology, genetics, and biochemistry. Some suggestions are made for increasing the impact factors of substance abuse journals if this is considered necessary. But instead of paying attention to the impact factor of a journal, scientists should give more consideration to the speed and efficiency of the editorial handling of their manuscripts and particularly to the quality and timeliness of the peer review. (+info)
Enhancing the identification of excessive drinkers on medical wards: a 1-year follow-up study.
This paper describes a 1-year follow-up study examining whether hospital ward doctors and nurses continue to take quantitative alcohol histories and provide brief intervention to problem drinkers on general medical wards after the introduction of a simple protocol. Regular training in the use of this protocol was stipulated in the annual service contract between the Health Authority and the Hospital Trusts. Improvements in staff practice persisted at 1-year follow-up, although it fell from a peak at an earlier phase of the study. The positive role of state purchasers of health services in sustaining improvements in clinical practice is discussed. (+info)
Urban-rural comparisons of drink-driving behaviour among late teens: a preliminary investigation.
A preliminary study was conducted to examine the nature and extent of urban-rural differences in self-reported drinking and driving among youths in Western Australia. A total of 102 youths aged 17, 18 and 19 years were surveyed via a random street sampling technique about their alcohol consumption and drink-driving behaviour. Analyses indicated that urban youths had a significantly higher level of self-reported drink-driving behaviour than their rural counterparts. Males indicated a higher level of self-reported drink-driving behaviour than females. This article also provides a review and summary of youth drink-driving literature with special focus on urban-rural comparisons. (+info)
Alcohol consumption profile by time in middle-aged men: a longitudinal study based on three different diagnostic instruments.
This longitudinal study aimed at comparing aggregate measures of heavy or problem drinking and their variations across time among the same subjects. We examined middle-aged men participating in a health survey over a 5-year interval. Of the 133 consecutive men in the whole age group interviewed as 40-year-olds in 1989, 114 were reached and re-interviewed in 1994. Alcohol consumption was measured by self-report, Malmo-modified Michigan Alcoholism Screening Test (Mm-MAST), and serum carbohydrate-deficient transferrin (CDT). Self-reported alcohol consumption decreased with years (142 vs 105 g/week, P = 0.01), as did CDT (16.9 vs 14.4 U/l, P = 0.02), but there was no change in the Mm-MAST results. There was no significant difference in the number of heavy drinkers (either Mm-MAST score > or = 3, or by self-reported alcohol consumption > or = 280 g/week, or by CDT > or = 20 U/l) at 40 and 45 years of age (37 and 47% respectively). At the individual level, alcohol consumption both increased and decreased with age. At 45 years of age 5/114 (4%) of the men reported that they had increased their alcohol consumption by more than 80 g/week and 25/114 (22%) said that they had reduced their drinking by the same amount. The remaining 84 (74%) reported drinking the same amount as 5 years earlier (+/- 80 g/week). This indicates that alcohol drinking habits are not stable in middle age. Most heavy drinkers in both age groups were detected by Mm-MAST and this proportion increased with age while the proportion of positive self-reports and CDTs decreased. Thus, the social consequences, measured here by the Mm-MAST, may be more readily experienced with years even at smaller consumption levels. (+info)