[Methodological approaches to the experimental investigation of dermotropic drugs].

Methodological approaches to preclinical evaluation of the efficiency of potential dermotropic preparations are proposed on the basis of original investigations and an analysis of published data. At the first stage of the preclinical investigation of preparations for external application, it is necessary to estimate their acute toxicity, allergenic activity, and local irritation effect in addition to studying the specific activity.

[Effect of histones on a change in the enzymatic activity of Escherichia coli and Staphylococcus aureus cells]. / Vliianie gistonov na izmenenie fermentativnoi aktivnosti kletok Escherichia coli i Staphylococcus aureus.

Histones have been found to interfere with the permeability of the cellular membranes of Escherichia coli and Staphylococcus aureus, this resulting in the liberation of 14C-amino acids, the UV-absorbing endogenous material, and the products of RNA degradation. Histones, particularly arginine-rich fractions, stimulated the RNAase activity of the bacteria. Histones inhibited the phosphatase activity of E. coli and stimulated that of Staphylococcus aureus. The ATPase activity of the cells increased upon contact with histones. These enzyme systems are presumed to be components of a mechanism whose activity increases upon the action on the cells of factors interfering with the permeability of the membranes so that low-molecular-weight compounds are liberated from the cells. It is possible that the RNAase, ATPase and phosphatase systems repair the pool of low-molecular-weight compounds, thus contributing to the survival of the bacteria.

[Effect of novoimanine on the cellular permeability indices of staphylococci]. / Vliianie novoimanina na nekotorye pokazateli kletochnoi pronitsaemosti stafilokokkov.

Novoimanine is an antibacterial drug from Hypericum perforatum L. When used in the bacteriostatic concentration, i.e. 0.5 gamma/ml, it induced release of potassium ions from the cells of Staphylococcus aureus 209P and had no effect on release of the UV-absorbing compounds and 14C-amino acids. In addition, incubation of the cells with novoimanine (2.5--50 gamma/ml) provided "preservation" in them of the earlier absorbed 14C-amino acids, while in the control cells their level decreased. In a concentration of 100 gamma/ml novoimanine stimulated activity of ATP-ase and alkaline phosphatase by 34 and 37-57 per cent respectively. Histones F1 and F3 of the calf thymus induced an intensive release of 14C-amino acids from the cells of staphylococci and increased the activity of ATP-ase by 6-10 times. The data of the study suggested that the effect of novoimanine on the cytoplasmic membrane was limited and different from that on the polycationic antibacterial agents.

[Effect of thymus histones on the RNAase, ATPase and phosphatase activity of staphylococcal cells]. / Vliianie gistonov timusa na RNK-aznuiu, ATF-aznuiu i fosfataznuiu aktivnost' kletok stafilokokkov.

It was shown that the representatives of different strains of Staphylococcus genus were characterized by a differential histone sensitivity. The membrane permeability increased in case of the bacterial contact with histones, and the degrading of the sum total cell RNA occurred in the contact of bacteria with histones. The RNA-ase, phosphatase, and the ATP-ase activity increased in the cells after their treatment with histones. The extent of expression of all these processes in the representatives of different strains correlated with their sensitivity to individual histone fractions. The problem that all the phenomena described indicated both the inhibitory effect of histones and some metabolic changes (permitting the cells to preserve their viability under unfavourable conditions) is discussed.

[Combination of novoimanine with antibiotics with a different mechanism of action]. / Sochetanie novoimanina s antibiotikami razlichnogo mekhanizma deistviia

Ampicillin, kanamycin, fusidic acid and rifocin significantly increased the effect of novoimanin on Staph. aureus 209. Histon F1 and spectinomycin did not influence the effect of novoimanin. Inefficiency of novoimanin combination with histon F1 provided a supposition that their effect may be directed to the same cell structures and most probably to the membranes. This was confirmed by the data of electron microscopy. The most effective combinations were recommended for the studies on their possible clinical use.

[Effect of histones on cell permeability, protein and RNA synthesis and RNA stability in Aerobacter cloaceae]. / Vliianie gistonov na kletochnuiu pronitsaemost', sintez belka, RNK i stabil'nost' RNK u Aerobacter cloaceae

The histones of calf thymus were found to change the permeability of the cells of Aerobacter cloaceae, without producing any noticeable effect on their viability. Concomitant depolymerization of the cellular RNA indicates destruction of the ribosomes. The increased synthesis of RNA in interpreted as a manifestation of reparatory processes. Protein synthesis, virtually unaffected in the resting cells, was inhibited to some extent in the growing culture treated with histones. Some considerations concerning the mode of action of histones at the intracellular level are presented.