[ Indicators of thiamine content and energy homeostasis in alcoholic psychosis]. / Pokazateli obespechennosti tiaminom i 'energeticheskogo gomeostaza organizma pri alkogol'nyx psikhozakh.

In dynamics of acute alcoholic psychoses--delirium and hallucinosis-- considerable deficit of thiamine in the organisms of ill people that can not be compensated while desintoxicative treatment and signs of energy homeostasis changes and of deterioration of tissues reserves depending on the type of psychoses were determined. Pathogenic peculiarities of the revealed disorders were analysed, possible compensative mechanisms connected in particular with the rise of pyruvate utilization speed and activation of glyconeogenesis while leaving the psychotic state were considered.

[Alcoholic dementia and divalent ions: derangement of calcium-homeostasis].

We proposed a hypothesis of disintegrated Ca-homeostasis underlying chronic alcoholism from our clinical viewpoints, and we suggest that the clinical features of alcoholism result from hypocalcemia or hypocalcemia induced by hypomagnesemia. Since the alcoholism brings on the divergent symptoms and signs, various diagnoses are made even for one patient, such as hypertension, cardiomyopathy, hepatitis, pancreatitis, Parkinsonian syndrome, neuropathy, muscle atrophy, epilepsy and osteoporosis. We speculate that these pathological conditions could be interpreted unitarily and systematically by hypothesis of Ca-abnormality.

[One of the methods of treatment of affective disorders in patients with alcoholism]. / Ob odnom iz metodov lecheniia affektivnykh narushenii u bol'nykh alkogolizmom.

It has been demonstrated by a double blind placebo-controlled study that transcranial electric treatment (TET) by means of combination of direct current and pulse current and pulse current at a frequency of 70-80 Hz is an effective method of correcting affective disorders (anxiety, depressions) in patients suffering from alcoholism. The therapeutic effects of TET are coupled with changes in GABA and monoamine metabolism rather than in beta-endorphin as well as with a decrease of the latent period of the occurrence of alpha-rhythm after eyes closing.

Impaired water excretion and elevated plasma vasopressin in patients with alcohol-withdrawal symptoms.

Reports describing the fluid balance status of alcoholics in withdrawal are varied, and conflicting. We examined this question by recording values for a variety of parameters in response to a standard water load test. Compared with age and sex matched healthy volunteers (n = 14), alcoholics in withdrawal (n = 17) exhibited lower cumulative urine output (p = 0.0001), higher minimum urine osmolality (p = 0.0001), lower serum sodium (p = 0.0024 before loading) and elevated plasma arginine vasopressin levels (p = 0.0045 before loading). We believe that these findings are best explained by a resetting of osmoreceptors, a supposition in keeping with contemporary views on the pathogenesis of alcohol dependence and withdrawal. This additional evidence of an antidiuretic state in alcohol withdrawal leads us to question the practice of fluid supplementation in its management and we suggest that this policy be revised.

[Decrease in the concentration of leukocyte acetylation coenzyme associated with vitamin precursor deficiency in patients with alcoholic delirium]. / Umen'shenie soderzhaniia kofermenta atsetilirovaniia leikotsitov v sviazi s nedostatochnost'iu vitaminnogo predshestvennika u bol'nykh alkogol'nym deliriem.

Sixty-three patients with the typical variant of delirium tremens were examined. The results showed a marked reduction (by 8.7 times) in levels of coenzyme A (CoA) in leukocytes, which was indicative of deficiency of the coenzymic form of pantothenic acid (PA). Changes in CoA concentrations in leukocytes observed at the height of psychosis in patients with alcoholic delirium as compared to other parameters of PA metabolism have great significance for the assessment of vitamin metabolism. PA deficiency was more expressed in cases of long-standing and massive alcoholization which induces an earlier development of psychosis. CoA levels in leukocytes may be used as a parameter of detoxication processes in patients with delirium tremens. The data obtained are considered as indication for administration of PA drugs in combined detoxifying therapy of alcoholic psychoses.

Brain marker protein changes after short- and long-term ethanol intoxication and withdrawal in the rat.

The brain marker proteins, D1, D2, and D3, localised to neuronal membranes, and mitochondrial and cytoplasmic marker proteins (MM and CM), were studied during 1-6 days (short term) intragastrically-induced severe ethanol intoxication and during 1 month (long-term) ethanol intoxication established by a liquid diet regimen. The concentrations of the same brain proteins were also measured during withdrawal from the ethanol intoxication periods. Three categories of effect were encountered: decreased concentration of brain marker proteins during severe short-term intoxication the effect being most marked for D3, possibly indicating degradation of mature synapses; increased concentration of proteins D2 and MM during withdrawal, the D2 changes possibly indicating formation of new synapses; increased concentration of D1 protein and MM during long-term intoxication. We suggest that the changes in brain marker proteins reflect dynamic changes of subcellular neuronal structures which may form a part of the basis of functional tolerance to and physical dependence upon ethanol or the reversion of these states after withdrawal of ethanol.

[Concentration of protein substances in neurons of different areas of the cerebral cortex in alcoholic delirium]. / Soderzhanie belkovykh veshchestv v neironakh razlichnykh oblastei kory golovnogo mozga pri alkogol'nom delirii.

The brain was studied in 11 cases of delirium tremens. Cytochemistry of nuclear and cytoplasmic protein levels in the neurons of the frontal and parietal cortex and the hippocampus was analysed. The findings were compared with the results of examinations in the control group (cases of sudden death of mentally healthy people). Examination of the brain from patients with delirium tremens revealed heterogeneous changes: a statistically significant reduction of protein levels in the neuronal cytoplasm in the frontal and parietal cortex and a negligible elevation of protein levels in the cytoplasm of the hippocampal pyramidal neurons. A considerable increase in protein levels was found in the nuclei of the hippocampus whereas cytochemical alterations in neuronal nuclei in the frontal and parietal cortex were less pronounced. The functional importance of the results obtained is discussed.

The effect of acute alcohol withdrawal on the serum potassium and total body potassium in heavy drinkers.

In a group of 20 patients with heavy alcohol intake a relation was found between withdrawal symptoms and fall in serum potassium. Total body potassium (TBK) was measured in all subjects and was lower in the group of subjects who displayed symptoms than in the group who did not. The subgroup of the four most severe reactors had a mean TBK value significantly less than the 'non-reactor' group. The minimum serum potassium levels observed for all subjects in the four day period following alcohol withdrawal correlated with their TBK values. We suggest that the mechanism for the serum potassium fall might be overactivity of the Na-K pump caused by ethanol consumption. There was also an association between withdrawal reaction and abnormal liver function and a transient rise in serum phosphate in the more severely reacting subjects.

Delirium tremens and related clinical states: changes in calcium and inorganic phosphate concentrations in plasma and cerebrospinal fluid.

Calcium and inorganic phosphate were measured in blood and cerebrospinal fluid (CSF) in 11 patients during impending delirium tremens (grade 2) and in nine patients with fully developed delirium tremens (grade 3). The initial sampling of blood and CSF was performed at admission before treatment was initiated. The blood sampling was repeated daily until recovery and at this time a second lumbar puncture was also performed. In grade 3 patients the plasma calcium concentration showed a transient increase after admission; in grade 2 patients the plasma calcium concentration was also somewhat elevated. The changes in plasma calcium concentration after admission correlated significantly with the changes in blood alcohol concentration. In grade 3 patients the CSF calcium concentration decreased between admission and recovery, this possibly relating to an increased cerebral binding capacity in the post intoxication period. No statistically significant changes were seen in either of the diagnostic categories as far as plasma inorganic phosphate concentrations are concerned. CSF inorganic phosphate concentration decreased in a fashion correlated with CSF alcohol concentration and, finally, CSF inorganic phosphate at admission was somewhat lower in grade 3 patients as compared to grade 2, this possibly reflecting a more severe disturbance of cerebral metabolism in grade 3 patients. Essentially, grade 3 patients had lower CSF concentrations of both calcium and inorganic phosphate as compared to grade 2 patients and thus there may exist real differences in the metabolism of these two ions when a severe withdrawal reaction (grade 2) is compared to fully developed delirium tremens (grade 3).

[Changes in the content of dense substances in the cerebral cortical neurons in alcoholic delirium]. / Izmenenie soderzhaniia plotnykh veshchestv v neironakh kory golovnogo mozga pri alkogol'nom delirii.

An autopsy of ten patients with alcoholic delirium involved histochemical examination of the cerebral cortex neurons including quantitative determination of solid substances (proteins) and the study of the intensity of the reaction of RNA in the nucleus and cytoplasm. The content of solid substances was determined with the help of the interference microscope BINAM L-211. To perform visual evaluation of RNA levels, the sections of the cerebral tissue were stained by Einarson's method. The data obtained were compared with the results of the study of the control group (cases of sudden death in mentally normal subjects). Alcoholic delirium was associated with a statistically significant reduction in the content of solid substances (proteins) in the neuronal cytoplasm; a diminished intensity of response to RNA was also noted. Neuronal nuclei showed similar but less marked changes.

Clinical conditions and concentrations of MOPEG in the cerebrospinal fluid and urine of male alcoholic patients during withdrawal.

The levels of 3-methoxy-4-hydroxyphenylethyleneglycol (MOPEG), the major noradrenaline metabolite in the central nervous system, were analyzed in lumbar cerebrospinal fluid (CSF) and urine from 74 male alcohol addicts during acute withdrawal and after 1 week of abstinence. The values obtained were compared to those of 21 healthy male volunteers. Clinical conditions were rated on the sampling days. Concentrations of MOPEG were elevated during early withdrawal and the levels decreased during detoxication. This pattern was found in both the CSF and urine, irrespective of type of drug treatment during withdrawal. The clinical symptoms improved during withdrawal and, in the beginning, there were significant positive correlations between MOPEG levels in the CSF and sleeping problems, tremors, restlessness, visual hallucinations, and elevated muscle tension. Changes in MOPEG levels correlated to changes of mood. A significant correlation was also found between low MOPEG level and craving for alcohol. Few correlations were found between MOPEG levels in the urine and clinical symptoms. The results indicate an elevated noradrenergic transmitter turnover rate in the early phase of alcohol withdrawal and a connection between noradrenaline metabolism and several clinical conditions during alcohol withdrawal.

Effect of ethanol administration and withdrawal on GABA receptor binding in rat cerebral cortex.

Sodium independent GABA receptor binding was measured in synaptosomes prepared from cerebral cortex of rats made ethanol dependent by three daily ethanol administrations. In rats sacrificed 1 hour after the last ethanol dose there was a lower number of low affinity binding sites and lower affinity of the high affinity binding than in controls. The decreased affinity was present only in rats who showed symptoms of ethanol withdrawal during the course of ethanol administration. In rats sacrificed during ethanol withdrawal the affinity of the high affinity binding was lower than in controls and other binding characteristics were unchanged. This decreased binding was normalized by repeated Triton X-100 incubations indicating involvement of an endogenous inhibitor in this ethanol effect. Acute ethanol administration did not change GABA receptor binding.

Magnesium concentrations in blood and cerebrospinal fluid during delirium tremens.

Magnesium in plasma, erythrocytes, and cerebrospinal fluid (CSF) was measured immediately after hospital admission in 9 patients with delirium tremens (DT) and 11 patients with impending DT. Blood samples were taken daily during the acute state; a second lumbar puncture was performed when the patient's condition had improved. Plasma magnesium was low in patients with DT during the first days of the acute state and then spontaneously normalized. Normal plasma magnesium was consistently seen among patients with impending DT. Magnesium in erythrocytes and CSF was normal in both diagnostic categories. Patients with a high blood-alcohol concentration (BAC) at admission had a decreasing plasma magnesium, patients with a low BAC had a moderately increasing plasma magnesium, and patients with a BAC at nil had a more marked increase in plasma toms or with their duration. This finding, combined with the normal CSF magnesium and the lack of correlation between plasma and CSF magnesium, indicates that disturbances in magnesium metabolism do not play a role in the etiology or pathogenesis of DT; but it may be that disturbances in magnesium metabolism contribute to the development of alcoholic encephalopathy.

Comparative simultaneous measurement of cerebrospinal fluid 5-hydroxyindoleacetic acid and blood serotonin levels in delirium tremens and clozapine-induced delirious reaction.

Cerebrospinal fluid 5-hydroxyindoleacetic acid and total blood serotonin levels were measured simultaneously in 11 female patients with delirium tremens and nine schizophrenic women with clozapine-induced acute delirium. Both groups had significantly raised levels of 5HIAA in CSF and significantly reduced blood 5HT levels as compared with normal control subjects, symptom-free alcoholics, or clozapine-treated schizophrenics. The two delirious groups were not distinguishable from each other in respect of their CSF 5HIAA or blood 5HT values. After clinical recovery both values returned to normal levels.