Comparative studies on the amino acid derivatives of indometacin

A series of amino acid derivatives of indometacin (IND) was investigated in regard to their protein binding and prostaglandin synthetase inhibition in vitro, and to acute toxicity, anti-inflammatory, antiedemic, analgesic actions, and the influence on the central nervous system in vivo. In biochemical tests the compounds were several times less potent than IND. They differed among themselves in the respect of toxicity, which was always much lower than that of IND. Out of eight compounds investigated N-IND-glycine (K1) and N-IND-epsilon-aminocaproic acid (K5) exerted more favorable antiedemic and analgesic action than IND did. Both the derivatives only weakly inhibited the cotton-pellet granuloma formation. K1 acted similarly to IND in the arthritis test. K1, K5 and IND similarly irritated the gastric mucosa. A modification of IND structure by introduction of glycine or epsilon-aminocaproic acid resulted in two new anti-inflammatory agents of more favorable therapeutic index in the antiedemic and analgesic action and of much lower toxicity than the reference compound.     

Cytogenetic examination of children with acute leukemia]

Cytogenetic examinations were carried out in 40 children with acute leukaemia. In 18 cases karyotype changes were demonstrated, in 8 cases the karyotype was normal, in 14 cases no cell division was obtained and these patients were excluded from further analysis. In the group with karyotype changes in most cases poor prognosis indices were found, including high number of blasts, extramedullary presence of leukaemic infiltrations and FAB L2 or L3. Chromosomal abnormalities included presence of aberrations in the form of translocation, mosaicism of karyotypes with nearly tetraploidy line, accessory marker chromosomes and other anomalies. In this group 8 children died (30% of all observed cases), while in the group without karyotype changes 2 children died (about 8%). In summary the authors stress the correlation between the presence of clinical prognostic factors (risk factors) and karyotype changes and worse prognosis in cases with chromosomal abnormalities. Attention is called to the great usefulness of cytogenetic examinations in the prognosis and treatment of leukaemias in children.     

Does damage of perivascular astrocytes in multiple sclerosis plaques participate in blood-brain barrier permeability?

In six young and two senile MS cases perivascular astrocytes within demyelination lesions were evaluated immunocytochemically. The peroxidase-antiperoxidase method of Sternberger et al. (1970) was used for visualization of glial fibrillary acidic protein (GFAP). In all cases very weak immunoreactivity of perivascular astrocytes was noted. Accumulation of perivascular glial fibers, and infrequently their fragmentation were observed both within active and old demyelination plaques. Clasmatodendrosis, Rosenthal's fibers and prominent regressive changes of astrocyte perikarya were found only in old plaques. A lack of immunoreactivity of perivascular astrocytes was noted within old demyelination lesions. The background of the latter was often immunonegative to GFAP. It is suggested that secondary damage of perivascular astrocytes influences vascular permeability within demyelination lesions including old plaques.     

Comparative studies on antidepressant action of alprazolam in different animal models

Alprazolam, a new benzodiazepine from triazolobenzodiazepine group, produced anxiolytic action in the conflict test with potency similar to that of diazepam. The myorelaxant activity of the drug was relatively weak. Unlike desipramine, alprazolam failed to reduce the immobility of rats in the forced swim test and was unable to prevent clonidine-induced hypothermia. Alprazolam, unlike desipramine, failed also to potentiate behavioral effect of noradrenaline injected into the hippocampus. Alprazolam after acute but not chronic administration antagonized the synchronizing effect of clonidine on EEG pattern. On the other hand, alprazolam similarly to tricyclic antidepressants, prevented the suppression of dominance behavior by clonidine in rats competing for food. The results indicate that alprazolam acts only weakly upon noradrenergic mechanisms related to depression and to antidepressant action of drugs.     

Malignant lymphoma of the eye

A case of primary malignant lymphoma of the eye in a 78-year-old woman is reported. A centroblastic non-Hodgkin lymphoma showed prominent involvement of the retina with massive serous retinal detachment. A review of the literature is given.