Allan D. Thomson

The influence of brain acetaldehyde on oxidative status, dopamine metabolism and visual discrimination task

The toxic effect of acetaldehyde on brain oxidative capacity and dopamine metabolism has been investigated in rat brains after a single intraperitoneal injection of acetaldehyde (5 mmol/kg) and the results compared with those from chronically ethanol fed rats. Acetaldehyde was present in rat brain 120 hr after a single dose of acetaldehyde, confirming that it is able to cross the blood-brain barrier. Brain catalase increased significantly after acetaldehyde or chronic ethanol administration although there were no other significant changes in the total brain activity of superoxide dismutase, glutathione peroxidase or glutathione reductase. Dopamine turnover was increased in both experimental groups. The acute dose of acetaldehyde reduced the ability of the rats to relearn a computer visual discrimination task.

PLASMA VITAMIN E STATUS IN CHRONIC ALCOHOLIC PATIENTS

Plasma vitamin E (alpha-tocopherol) concentrations were estimated by high performance liquid chromatography (HPLC) in 50 consecutively admitted chronic alcoholics (M = 44;F = 6;mean age +/- S.D. = 42.94 +/- 10.97;age range = 28-70 years) on admission and in 25 of them it was repeated during abstinence (6th day) while undergoing conventional detoxification therapy with polyvitamins (except vitamin E) and hypno-sedative drugs. Thirty percent of the patients were found to be deficient on admission and while on routine hospital diet during therapy, 20% of the patients were still deficient. It is, therefore, suggested that chronic alcoholics should be treated routinely with vitamin E along with other polyvitamins during detoxification in alcoholic units.

THYROID STATUS IN CHRONIC ALCOHOLICS

Serum thyroxine (T4), triiodothyronine (T3) and thyrotrophin (TSH) were measured by radioimmunoassay in 39 chronic alcoholics on admission. Two patients had a reduced circulating serum T4 and eight showed a low serum T3 level but basal TSH was not raised in any of the 39 patients. Interestingly, low T4 and T3 levels returned to normal after abstinence and high protein and vitamin supplemented diet for one week. It is clear from our observations that a normo- or hypo- rather than a hypermetabolic or hyperthyroid state is more common in drinking chronic alcoholics. Ethanol-induced low T3 syndrome has also been described and a mechanism of its pathogenesis is suggested.

Changes in plasma amino acid patterns in chronic alcoholic patients during ethanol withdrawal syndrome: Their clinical implications

Changes or imbalances in plasma amino acid patterns during withdrawal from ethanol were recorded in six randomly selected male chronic alcoholic patients (age range 23-47 years). Duration of drinking ranged from 4-15 years and their average daily amount of ethanol intake was more than 100G. Plasma amino acids (taurine, threonine, serine, glutamate, glutamine, proline, glycine, alanine, cysteine, valine, methionine, isoleucine, leucine, tyrosine, phenylalanine, histidine, tryptophan, ornithine, lysine and arginine) were estimated by autoanalyzer in all patients on admission before starting conventional detoxification therapy for ethanol withdrawal syndrome, and during therapy on day 3 and day 6. On admission, there was a statistically significant rise in the plasma levels of almost all aminoacids, particularly glutamate, glutamine, phenylalanine, proline, glycine, methionine, cysteine, lysine, tyrosine, valine, isoleucine, leucine, serine, threonine, alanine and arginine (in comparison to those of normal controls) in five out of six patients. During the following six days of treatment and total abstinence, the pattern of plasma aminoacid levels did not change significantly despite considerable clinical improvement. Plasma tryptophan levels were undetectable in all patients on admission, day 3 and also on day 6 except in one patient with lesser amount and shorter duration of drinking, the levels just returned to within normal range only on day 6. Plasma levels of histidine and taurine were found to be slightly lower than normal.

Plasma urea and creatinine status in chronic alcoholics

Plasma urea and creatinine concentrations were estimated by Auto-Analyzer in 128 chronic alcoholics (103 males, 25 females; mean age +/- SD = 42.73 +/- 6.53; age range 20-60 years). Plasma levels of both urea (mean +/- SD = 3.46 +/- 1.31; normal range 2.0-6.5 mmol/l) and creatinine (mean +/- SD = 87.86 +/- 15.45; normal range 60-120 mumol/l) were found to be within normal limits. It is concluded from our observations that chronic ethanol ingestion per se is not nephrotoxic. The kidney seems to be the only vital organ generally spared in chronic alcoholics without advanced alcoholic liver disease or hepato-renal syndrome.

The effect of naftidrofuryl on ethanol-induced liver damage in chronic alcoholic patients

A prospective double-blind placebo-controlled trial of intramuscular Naftidrofuryl was carried out on 32 randomly selected hospitalized male alcoholic patients with clinical, biochemical and histological evidence of hepatic damage. Seventeen patients received the drug (40 mg in 5 ml i.m. three times daily for 6 days) and 15 patients received a placebo (5 ml in normal saline i.m. three times daily for 6 days). The drug was well tolerated and there were no adverse side-effects. Naftidrofuryl significantly improved the physiological function of the liver cells as reflected by indocyanine green (ICG) clearance by the liver (t = 2.61; p less than or equal to 0.02) and also caused a larger fall in raised serum levels of gamma glutamyl transpeptidase (GGT) than did the placebo injections. Overall clinical improvement (e.g. appetite, body weight, reduced liver size, general sense of well-being) was more clearly evident in patients of the treated group than in those of the placebo group. Naftidrofuryl, therefore, appears to be of benefit in ethanol-induced liver damage and more extensive long-term trials are suggested in patients with alcoholic liver disease (ALD).

Serum zinc, magnesium and calcium status in the Wernicke-Korsakoff syndrome

The Wemicke-Korsakoff Syndrome is a rare but extremely disabling noninfective neuro-psychiatric complication of chronic alcoholism, which is clinically characterized by dementia, disorientation, ataxia, confabulation, ophthalmoplegia, depression, agitation, peripheral neuropathy, etc. It may be due to deficiency of thiamine (Vitamin B,) [l] and magnesium ions have been reported to be necessary for the utilization of thiamine [ 21. Secondly, zinc has been suggested to have a possible role in the pathogenesis of dementia [3]. Thirdly, cholinergic system seems to be involved in the biochemical pathology of dementia [4] and calcium ions are involved in the release of the neurotransmitter acetylcholine [ 51. In view of these observations, this paper reports on the serum status of zinc, magnesium and calcium in fifteen patients with Wemicke-Korsakoff Syndrome.