Search

1. Mefloquine, a phospholipid interacting antimalarial drug, inhibits Ca2+ stimulated phospholipid dependent protein kinase from rat spleen by interfering with the activation process. 2. The type of inhibition was found to be competitive with respect to phosphatidylserine; the apparent Ki-value was determined to be 60 microM.

A potent inhibition of arginyl-tRNA-synthetase from Dirofilaria immitis by N-[4-(4'nitroanilino)-phenyl]-S-(beta-carboxylethyl)-dith iocarbamic acid-ester (CGP 8065) is demonstrated, which indicates the charging of amino acids to tRNA as a possible target for the chemotherapeutic attack by this filaricidal compound. CGP 8065 competes with ATP; the inhibition constant was determined to be 13 micrograms ml-1 (34 microM). The Michaelis constants for arginine and ATP were found to be 5 microM and 0.4 mM, respectively. The inhibition of arginyl-tRNA-synthetase by CGP 8065 was shown to be specific for D. immitis; the isofunctional enzymes from Ascaris suum and rat liver were not affected.

Dolichol kinase, a rate limiting enzyme for the supply with dolichyl monophosphate as glycosyl carrier lipid, was demonstrated in Plasmodium falciparum. The enzyme was found to be associated with the pellet fraction and to depend on cytidine triphosphate as phosphoryl donor. The apparent Km values of the plasmodial enzyme were determined to be 0.8 mM for cytidine triphosphate and 17 micrograms ml-1 for dolichol. In the presence of 0.5 mM mefloquine, the inhibition of enzyme activity was found to be about 50%.

Two cyclic AMP-binding proteins, not identical with regulatory subunits of protein kinases, have been isolated from Trypanosoma gambiense. The cyclic AMP receptors were separated by gel chromatography on the basis of their molecular weights. The binding constants of the high and the low molecular weight receptors for cyclic AMP were determined to be 0.4 muM and 0.6 muM, respectively. Cyclic IMP and cyclic GMP compete with cyclic AMP for the binding sites of both receptors. The cyclic AMP binding of the low molecular weight receptor was competitively inhibitied by adenine derivatives. The binding capacity of the high molecular weight receptor was enhanced about two-fold by proteolytic modification with trypsin.

Plasma 17-OH corticosteroid levels were determined before stimulation and at various intervals after stimulation in these limbic sites in patients in whom implanted electrodes had been placed during evaluation for surgical treatment of psychomotor epilepsy. Stimulation of the amygdala was followed by an elevation of plasma 17-hydroxycorticosteroids. Hippocampal stimulation resulted in a decreased corticosteroid level, followed in two instances by a secondary elevation.

In a preliminary study of 52 patients with cerebral vascular disease, clinical and electroencephalographic evaluations were compared. Most of the patients were in the sixth and seventh decade of life and had had symptoms of cerebral vascular disease for over a year. Seventeen of the patients had clinical evidence of intermittent cerebral ischemia. When routine electroencephalographic techniques were used, 47 per cent of the records were within normal limits. Twenty patients with cerebral vascular disease, eight of whom had clinical cerebral vascular insufficiency, were studied during posturally induced hypotension. No activation was detected in any of these 20 patients. It would appear that other methods of activation, including tilt-table studies, and serial recordings should be further explored and evaluated in these disorders if more clinically useful information is to be gained.

Temporal lobe epilepsy appears to be of increasing concern to psychiatrists, pediatricians and lawyers as an explanation for some aspects of behavior. There is a high incidence of structural abnormality associated with temporal lobe epilepsy, the most common being mesial temporal sclerosis. Depth electrode studies have shown that the most common focus for the clinical seizure is in the hippocampus or hippocampal gyrus. The first line of treatment continues to be attempt at control with anticonvulsant agents. Surgical treatment can be offered, in many instances, when drug therapy has failed.