The effects of chronic dietary phenytoin on 5-HT and 5-HIAA levels in rats

Rats were given, by means of the diet, phenytoin (PHT) every day for either 4 (400–800 mg/kg) or 14 (400 mg/kg) weeks. Serum values of PHT in both cases were in the pharmacological range (10–15 μg/ml). An increase in brain 5-HIAA levels was noted after 4 but not 14 weeks of PHT administration. There was no change in brain 5-HT levels. In accordance with results in epileptic patients, it appears that under some circumstances, PHT can increase 5-HIAA levels, but the mechanism of this action is unknown.     

Hypoglycemic coma in chronic alcoholism]

The authors present two cases of chronic alcoholism in two female patients aged 41 and 52 years without diabetes mellitus, in whom hypoglycaemic coma occurred during the abstinence period. Hypoglycaemia in one patient occurred suddenly as a result of fasting within 24 hours following the last alcohol intake, whereas a severe hypoglycaemia in the second patient was developing progressively during 72 hours; patient did not eat much and the last meal took 24 hours before the onset of hypoglycaemic coma. Diagnosis of hypoglycaemic coma was suspected because as no alcohol or acetic acid smell were felt, no alcohol or methanol was detected in blood (tested only in one patient). Adrenergic reactions were not distinct (no excessive sweating, convulsions, tachycardia). The authors suggest, that a severe hypoglycaemia should be considered in patients suspected of alcoholism, and the treatment should start earlier with intravenous glucose administration.     

Relation between brain 5-HIAA levels and the release of serotonin into brain synapses

Our findings in experiments using reserpine, an amine releaser, and fluoxetine, a serotonin uptake blocker, indicate that the reuptake of serotonin from brain synapses precedes its transformation to 5-hydroxyindoleacetic acid (5-HIAA). Male rats were injected with reserpine or fluoxetine alone, or with fluoxetine one hour before reserpine; control animals received diluents. Reserpine lowered brain serotonin and raised brain 5-HIAA levels. Fluoxetine alone did not change serotonin levels but lowered 5-HIAA. Fluoxetine completely antagonized the reserpine-induced increase in 5-HIAA, and significantly enhanced its depletion of serotonin. In order to determine whether the ability of fluoxetine to block the rise in 5-HIAA after reserpine resulted from its effect on serotonin reuptake or from suppression of impulse flow along serotoninergic neurons, we also examined the effects of the drugs on serotonin metabolism in distal portions of acutely transected neurons (which, presumably, were no longer able to conduct impulses). No differences were noted between the responses of intact and lesioned serotoninergic neurons, indicating that fluoxetine's blockade of the rise in brain 5-HIAA results from its effect on serotonin reuptake.     

Disturbances in catecholamine metabolism during formation and development of chronic alcoholism]

There has been carried out an investigation dealing with catecholamines metabolism in the patients suffering from alcoholism in the first, second and third stage at the short-term remission. The first developed alcoholism stage was determined as a typical one for increasing the excretion with urine of DOPA, dopamine (DA), noradrenaline (NA) and adrenaline (A), as well as the blood levels of DA, NA and A. DA/NA rate evidences about an increased synthesis of NA with DA. The marked second alcoholism stage is characterized by an acute decrease of excreting with urine and blood levels of NA. Alongside with the latter. DA excretion with urine and its blood levels remained high. DA/NA rate indicates to the considerably low relative activity of NA with DA synthesis, both in relation to the control and to the developed first alcoholism stage. In the third alcoholism stage NA excretion with urine and its blood levels become lower relatively to the marked second stage. Simultaneously DA excretion with urine and its blood levels are lower than in the developed second stage, hower exceed the control values. DA/NA rate testifies the slight activation of NA and DA synthesis. The results obtained in the work indicate to the significant role of CA metabolism disturbances in the alcoholic dependence formation.     

5-HT and 5-HT-SO4, but not tryptophan or 5-HIAA levels in single feeding neurons track animal hunger state

Serotonin (5-HT) is an intrinsic modulator of neural network excitation states in gastropod molluscs. 5-HT and related indole metabolites were measured in single, well-characterized serotonergic neurons of the feeding motor network of the predatory sea-slug Pleurobranchaea californica . Indole amounts were compared between paired hungry and satiated animals. Levels of 5-HT and its metabolite 5-HT-SO₄ in the metacerebral giant neurons were observed in amounts approximately four-fold and two-fold, respectively, below unfed partners 24 h after a satiating meal. Intracellular levels of 5-hydroxyindole acetic acid and of free tryptophan did not differ significantly with hunger state. These data demonstrate that neurotransmitter levels and their metabolites can vary in goal-directed neural networks in a manner that follows internal state.     

Hematologic complications in acute alcoholism]

The authors investigated the relations between cell anomalies (vacuolation, increasing sideroblastosis) caused by the uptake of alcohol and the dynamics of haematopoesis in the bone-marrow of 33 alcoholists who had been admitted in a comatose condition and who were neither affected with anaemia nor with chronic hepatitis. In all cases a maturation arrest of erythropoetic and granulopoetic cell elements which was not in accordance with the number of immature vacuolated cells could be observed. 12 test persons showed increased sideroblastic indices and a slightly diminished medullary reticulocytosis. The majority showed a very active thrombocytopoesis contrasting with the normal or even diminished number of thrombocytes in the peripheral blood. The authors come to the conclusion that alcohol will cause a general metabolic damage of haematopoesis and at the same time it will produce a direct toxic effect on the bone-marrow cells (proerythroblasts, promyelocytes) and the peripheral blood (thrombocytes).     

Increased levels of gamma-glutamylamines in Huntington disease CSF

Transglutaminases (TGases) catalyze several reactions with protein substrates, including formation of γ-glutamyl-ε-lysine cross-links and γ-glutamylpolyamine residues. The resulting γ-glutamylamines are excised intact during proteolysis. TGase activity is altered in several diseases, highlighting the importance of in situ enzymatic determinations. Previous work showed that TGase activity (as measured by an in vitro assay) and free γ-glutamyl-ε-lysine levels are elevated in Huntington disease (HD) and that γ-glutamyl-ε-lysine is increased in HD CSF. Although free γ-glutamyl-ε-lysine was used in these studies as an index of in situ TGase activity, γ-glutamylpolyamines may also be diagnostic. We have devised methods for the simultaneous determination of four γ-glutamylamines in CSF: γ-glutamyl-ε-lysine, γ-glutamylspermidine, γ-glutamylputrescine, and bis-γ-glutamylputrescine and showed that all are present in normal human CSF at concentrations of ∼150, 670, 40, and 240 nM, respectively. The high γ-glutamylspermidine/γ-glutamylputrescine and γ-glutamylspermidine/bis-γ-glutamylputrescine ratios presumably reflect in part the large spermidine to putrescine mole ratio in human brain. We also showed that all four γ-glutamylamines are elevated in HD CSF. Our findings support the hypotheses that (i) γ-glutamylpolyamines are reflective of TGase activity in human brain, (ii) polyamination is an important post-translational modification of brain proteins, and (iii) TGase-catalyzed modification of proteins is increased in HD brain.