In vivo and in vitro research on the biological effects of deuterium-depleted water: 1. Influence of deuterium-depleted water on cultured cell growth.

Deuterium depleted-water (DDW) is a new available tool for decreasing deuterium concentration in the environment of cells in culture. Several types of established cell lines, both normal and neoplastic were grown in culture media dissolved with DDW and compared with the same strains, in the same amounts, grown in media dissolved with normal distilled water. Naive mice splenocytes were grown, under stimulation with proliferation triggers, like bacterial lipopolysaccharide (LPS) and Concanavalin A (ConA) in the same conditions. The growth and proliferation were estimated using the MTT assay. Both established cell types and explanted splenocytes in the DDW-media had a significantly higher growth rate than cell cultured in normal media. In an attempt to identify the membrane mechanisms involved in the growth stimulation by DDW, the membrane proton transporters Na+/H+ antiporter and H+/K+ATP-ase were inhibited with their selective blockers amiloride and respectively lansoprazole. The results, however incomplete, point towards a lack of involvement of the Na+/H+ antiporter and a possible implication of the H+/K+ATP-ase.

[Synthesis of new mandelic acid derivatives with preservative action. Synthesis and acute toxicity study]. / Sinteza unor noi derivati ai acidului mandelic cu actiune conservanta. Sinteza si studiul toxicitatii acute.

Starting from the antiseptic action of DL mandelic acid, there were synthesized a series of esters of the mandelic acid, esters which could have preservative action. This study present the synthesis, structure validation and the acute toxicity study, for the new synthesized compounds. The esters were obtained by acylating 4-hydroxybenzoic acid propyl, ethyl, methyl esters and salicylic acid with the DL mandelic chloride (that was protected initially by the hydroxylic group). The structure of the synthesized compounds was confirmed by quantitative elemental analysis and RMN 1H spectral measurements. The acute toxicity was determined for two of the esters, who proved to had a preservative action (previously studied) and indicated that these esters have a small toxicity.

[An experimental study of tolerance to benzodiazepines]. / Cercetare experimentala a tolerantei la unele benzodiazepine.

The intention of the study was to demonstrate the appearance of the tolerance phenomenon after repeated administration of three of the most used benzodazepines (BDZ): Diazepam, Alprazolam and Oxazepam using three pharmacological tests, which monitored the neuromotor coordination, the myorelaxing and the anxiolitic effect. For each drug were used 3 doses, in geometrical progression, beginning with the partial dose, extrapolated from human to mouse according to the body surface. The treatment was made once a day, during 4 days. The appearance of tolerance was noticed, meaning an approximately 4-fold decrease of the sedative effect after the repeated administration of the 3 BDZ for all doses used. No tolerance was shown for the anxiolytic and myorelaxing effects, with the exception of alprazolam, which induced tolerance also for the myorelaxing effect. Our study has shown that repeated administration of BDZ might have different consequences on their pharmacological spectrum. The study indirectly explains the success of Alprazolam in therapy. This is due to the fact that small doses have approximately the some efficiency as the big ones in unique administration, decreasing the abuse potential. The rapid onset of the tolerance for the sedative and myorelaxing effect recommends its long-term administration in anxiolytic therapy.