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Estrogens play the most important role in breast cancer oncogenesis. There are different methods used to decrease estrogen production and serum concentration: surgery, irradiation and drug-based method. In the current study 500 patients with localized surgically resectable breast cancer (infiltrative-edematous form included) or disseminated breast cancer with indication for ovarial function inhibition. The patients were divided into 3 groups. The first group consisted of 400 patients with prior endoscopic bilateral ovariectomy. The second group included 50 patients with prior ovarian irradiation, the third one included 50 patients after laparotomic ovarian resection. The results obtained show 100% effect of endoscopic ovariectomy resulted in disabled ovarian function, which is more effective, than ovarian irradiation (92%). Besides, the endoscopic method doesn't have negative effects characteristic for irradiation, such as involvement of non-target organs or restoration of hormone production. Endoscopic surgery was characterized by 10-fold decrease in complications rate compared to laparotomic operation (2.2% vs 24%). Besides, endoscopic intervention leads to much shorter inpatient treatment duration and demand for anesthetics and antibiotic treatment making it less costly, than more traditional methods of castration. Therefore, endoscopic ovarian resection is a safe and effective castration method in breast cancer patients.

The study of changes in the intracellular processes during differentiation of myoblasts into myotubules is of great importance for understanding several fundamental problems of cell biology. At first, this concerns the spatial organization of vacuolar apparatus that reflects the alterations in the properties of cell membranes, cytoskeleton elements and dynamics of vesicular transport in the course of differentiation. The distribution of acidic membrane organelles (lysosomes, late endosomes, Golgi cisternae) during the myotubule formation was revealed. It was shown that perinuclear localization of acidic organelles in myoblasts was replaced by diffuse distribution of these structures in the whole volume of myotubules. Using lipophilic fluorescent dyes, RH 414 and di-8-ANEPPS, the process of formation and dynamics of endocytic vesicles in myoblasts and myotubules was investigated. In the present work, semiconductive nanocrystals, quantum dots (QDs), conjugated with TAT-peptide, which belongs to cell-penetrating peptides, were used to characterize nonspecific endocytosis. It was shown that QDs--TAT complexes penetrate myoblasts but do not penetrate myotubules even after 24 h incubation, which might be connected with plasma membrane changes during the process of skeletal muscle differentiation.

Analysis of archival records on the activity of diurnal plane-tables from the region's weather stations revealed local radioactive fall-out in the near-Baikal areas from the nuclear weapon tests carried out at the Semipalatinsk testing site. Examination of mortality rates in the settlements exposed to the tests showed that the maximum rates of overall and lung malignancy mortalities were observed in 1960-1979; the mean radiation dose in the exposed settlements were estimated to be 580-850 MeV.

Using spectral scanning regime of Leica TCS SL confocal microscope, acridine orange (AO) fluorescence spectra in nuclei and cytoplasms of living myoblasts L6J1 and frog single muscle fibres have been studied. AO fluorescence spectra in salt solutions dependent on free AO concentrations and in AO complexes with DNA have also been obtained for comparison. Myoblasts nuclei fluoresced in green spectral region with maximum at approximately 530 nm (corresponding AO monomers fluorescence), nucleoli fluoresced most brightly. Nuclear chromatin fluoresced not uniformly in these cells. We saw similar to myoblasts AO emission in nucleoli and nuclei of frog single muscle fibres. The uniformed weak green fluorescence was observed for myoblast cytoplasm. As to the muscle fibres sarcoplasm, we saw also AO green fluorescence in A-discs. In myoblasts and muscle fibre cytoplasm we saw the fluorescent red, yellow and green granules which were acidic organelles. The comparison of AO fluorescence spectra in living cells with fluorescence spectra of different AO concentrations and complexes of AO with DNA in buffer solutions allows estimation of AO concentration in acidic granules which is of interest in the investigation of cellular organelles functions in the processes of intracellular transport, adaptation, apoptosis and a number of pathological conditions.

The problem of non-specific binding of quantum dots (QDs) with cells is very important but not fully understood taking into account the possible application of QDs in medical and fundamental studies. The interactions of untargeted CdSe/ZnS QDs with isolated frog muscle fibres, HeLa cells and J774 cells were investigated. The observations were performed on living cells using laser confocal microscopy (Leica TCS SL). The QDs covered with polyethylenglycol without any functional reactive groups with emission maximum at 565 nm were used in the study. This type of QDs is suggested to prevent an interaction of QDs with biological molecules. It has been shown that QDs do not enter HeLa cells, T-system and sarcoplasm of skeletal muscle fibres. However, during long-term incubation J774 cells can uptake QDs. The data obtained has demonstrated the diversity of interactions of untargeted QDs with different cell types and are important for understanding of the problems of non-selective uptake and cytotoxicity of QDs.

Medico-dosimetric register is an optimal model of epidemiological studies on evaluation of ionizing radiation effects. Regional medico-dosimetric register (RMDR) is a system of interrelating information blocks including data on Siberian Group of Chemical Enterprises (SGCE) personnel. At present SGCE personnel and Seversk residents RMDR database includes information on 138496 persons, 65538 of which are SGCE workers. SGCE personnel and Seversk residents RMDR is a scientific base for researches with the aim of evaluating long-term ionizing radiation effects in a "low" dose range. Information on mortality and morbidity rate as well as "thematic" registers of the main diseases potentiates in evaluating the spectrum of somatic stochastic effects and radiogenic risks in SGCE workers and Seversk residents as well as their offsprings. A practical significance of RMDR database is the formation of the main diseases "risk" groups depending on definite risk factors in certain groups that provides targeted diagnostic and preventive therapy both among high-dose establishments' workers and residents living near-by.

The changes of T-system and cellular acidic organelles during spreading (Zenker's) necrosis of frog skeletal muscle fibres have been investigated using laser confocal microscopy and several vital fluorescent dyes acridine orange, RH 414, DiOC6(3), rhodamine 123, fluorescein dextran. The formation of numerous vacuoles as a result of local T-system swelling is most characteristic for initial steps of Zenker's necrosis. Vacuoles can attain tens microns in length. They are located both near nuclear poles and between myofibres. Vacuoles maintain connections with the extracellular space up to the moment of contraction knot rejection, and under definite conditions (glycerol influx to fibre) vacuoles are reversible. They deform nuclei and sarcoplasmic reticulum cisternae. Cellular acidic organelles, accumulating acridine orange (lysosomes, late endosomes, Golgi apparatus cisternae) are situated in direct vicinity with normal and vacuolated T-system. The increase in acidic organelles number and size occur during the pathological process development, and tendency to vacuoles clusterization may be seen. Vacuolation of T-system during necrosis is not followed by vacuole content acidification. The role of cellular acidic organelles and of T-system vacuolation in the development of different muscle pathological changes is discussed.

A study was made of modulations of lysosome-phagosome fusion process and of fibrillar actin content in mouse peritoneal macrophages by an antitumor alkaloid sanguinarine and a derivative drug Ukrain. In addition, effects of these substances on in vitro polymerization of monomeric globular actin from rabbit muscle were investigated. Sanguinarine and Ukrain stimulated lysosome-phagosome fusion and increased the content of polymerized fibrillar form of actin in mouse macrophages. Effects of these substances were enhanced at their higher concentrations. Both sanguinarine and Ukrain induced in vitro polymerization of globular actin from rabbit muscle. A possible role of sanguinarine and Ukrain in changing vesicular membrane states during intracellular membrane interaction in lysosome-phagosome fusion process was discussed. The influence of these substances on actin polymerization and actin cytoskeleton rearrangement was evaluated. It could be supposed that sanguinarine and Ukrain may alter intracellular membrane transport.

By means of fluorescent and phase-contrast microscopy the distribution of acid membrane organelles in normal and vacuolated frog skeletal muscle fibers has been studied. The vacuolation of the T-system was produced by loading and subsequent removal of glycerol (80-110 mM), or it appeared as a result of Zenker's necrosis. Acridine orange (AO) was used as a marker for acid intracellular compartments. AO accumulated in granules localized near the nuclear poles (more seldom around the nucleus)' and in the intermyofibrillar spaces. Typically the AO granules make up short longitudinal chains or regular pairs, where the distances between neighboring granules are short-dated to sarcomere lengths. Almost all granules emit in red, but about one third of them simultaneously emit in green, which is characteristic of AO monomers. In the vicinity of necrotic boundary or under the influence of brefeldin A, a green component of fluorescence appears in most granules. Treatment with monensin leads to granule disappearance. Vacuoles accompanying the glycerol treatment or developing of necrosis do not accumulate AO and exert no effect on the localization of AO-granules. The nature of cellular organelles accumulating AO in skeletal muscle fibers is discussed.

Polyethylenimine (PEI) and cationic polypeptides complexed with plasmid DNA are the most efficient nonviral vectors for gene therapy. It is believed that endocytosis is the major pathway for cell entering by PEI/DNA or cationic peptides/DNA complexes. Effects of plasmid DNA complexed with PEI, poly-L-lysine (PLL), poly-D-lysine (PDL) and polyarginine (PA) on the phagosome-lysosome fusion (P-LF) were studied in murine peritoneal macrophages and J774 macrophages. Cationic polypeptide PLL can be hydrolysed by cellular peptidases, but its stereoisomer, PDL, cannot be split by these enzymes. PEI, PDL, and PA have been shown to inhibit P-LF. PLL showed a low effect on the P-LF. On the basis of these studies, we assume that lysosomotropic agents able to change functions of lysosomes in the cell may affect transfection efficiency and thus be used for gene therapy.

The paper reports a lethal outcome of recurrent myocardial infarction in a male patient who in 1996 survived a massive infarction of the right ventricle posterior wall resulting in formation of a giant petrificate with a softening in the center. Connective tissue growth and cardiomyocytic atrophy was histologically revealed in the surrounding tissue. The patient died in 1999 of the infarction of the anterior wall of the left ventricle.

The changes in cytosol Ca2+ concentration associated with the shrinkage of Arabidopsis cells induced by the inhibitor of Ca(2+)-ATPase, cyclopiazonic acid and the Ca2+ ionophore ionomycin were monitored using the fluorescence of Ca(2+)-sensitive probe chlortetracycline hydrochloride. It was found that these compounds elicited a substantial decrease in fluorescence intensity closely associated with Ca(2+)-release from the intracellular stores to the cytoplasm. The release of Ca2+ from the intracellular depots was accompanied by decrease of plant cell volume. Thapsigargin and 2,5'-ditert-butyl-1,4-benzohydroquinone (highly specific inhibitors of Ca(2+)-ATPase of endoplasmic reticulum) resulted in much weaker changes than cyclopiazonic acid did. It was also found with the help of the same technique that red light (lambda = 660 nm) illumination induced a similar Ca2+ release from the intracellular stores. Moreover, the amplitudes of light-induced fluorescence responses registered in mutant plants differing in the content of phytochrome A (phyAOX) and phytochrome B (phyBOX) were much higher than those registered in wild-type of Arabidopsis.

Effects of polyamine (PA) synthesis inhibitors--alpha-difluoromethylornithinchloride (DFMO) and alpha-methylornithinchloride (MO)--separately or in combination with the epidermal growth factor (EGF)--on lysosome-phagosome fusion (P-LF) and F-actin content in murine peritoneal macrophages were studied using fluorescent dye Acridine orange for lysosome labelling, FITC-phalloidin for F-actin, and yeast cells as a target. DFMO and MO significantly inhibited P-LF and decreased F-actin content in murine peritoneal macrophages. A combination of DFMO and MO with EGF failed to inhibit P-LF or to decrease F-actin content in these cells. The results obtained with DFMO and MO suggested new cellular targets of their effects. These results may be extended to cancer research to provide a rationale for clinical trials using combinations of EGF with DFMO or MO.

In free-living Amoeba proteus (strain B), acid phosphatase (AcP) was examined by disc-electrophoresis in polyacrylamide gel. The tartrate-sensitive amebian AcP was greatly inhibited by dithiothreitol and Cu2+, and only partly inhibited by sodium orthovanadate, ammonium molybdate, EDTA, disodium salt and Mg2+, Ca2+, Zn2+ and Mn2+. On the contrary, it appeared to be resistant to sulfhydryl reagents--4(hydroxymercury) benzoic acid, sodium salt and N-ethylmaleimide. Unlike the tartrate-sensitive enzyme, the tartrate-resistant AcP was greatly inhibited by EDTA and partly inhibited by dithiothreitol, Mg2+ and Cu2+ (Mn2+ > Cu2+), being activated by orthovanadate, molybdate, sulfhydryl reagents, Mg2+, Ca2+ and Zn2+. Both tartrate-sensitive and tartrate-resistant AcPs lack apparently free SH-groups necessary for their catalytic activities. Using 2-naphthyl phosphate as a substrate at pH 4.5, six AcP electromorphs were revealed in cytosol and sediment, four of these being most frequently localized in the former, and two in the latter. Two other AcP electromorphs were confined to the sediment only. Depending on the quantity of sedimented amoebae making a homogenate (0.5 or 2.0 cm3), that was added to Percoll solution, the lysosomal AcP fraction in polyacrylamide gel was represented by one or two tartrate-sensitive electromorphs. Therefore, tartrate-resistant AcP in A. proteus may be a lysosomal enzyme, while tartrate-resistant AcP may correspond to serine/threonine protein phosphatase.

Effect of DNA-intercalators ethidium bromide (EB, 0.005 and 0.015 mM) and dimidium bromide (DB, 0.005 and 0.010 mM) and antioxidative compounds acetylsalicylic acid (ASA, 0.05 and 0.50 mM) and beta-carotene (0.01, 0.02, 0.05 mM) on the phagosome-lysosome (P-L) fusion and F-actin content in murine peritoneal macrophages were studied. EB, DB, ASA and beta-carotene were found to stimulate P-L fusion and the effect depending on the concentration of compounds tested. The strongest influence as evoked by 0.5 mM of ASA and 0.05 mM of beta-carotene. The compounds tested enhanced the F-actin content in macrophages, especially by the action of beta-carotene (0.05 mM). The obtained data indicate a correlation between P-L fusion stimulation and F-actin content under the influence of compounds tested in murine peritoneal macropheages.

Common molecular and cellular targets for alkaloids sanguinarine and ellipticine, isolated from well-known antitumor plants (as well as from their various natural and synthetic derivatives), have been studied and described. Sanguinarine and ellipticine are characterized by significant biological activities including a high antitumor potential. Among the important targets of their action the following are to be noted. 1. DNA and other double helical polynucleotides. Due to the ability of DNA-intercalation sanguinarine, ellipticine and some of their derivatives can modify the double helical structures and topological forms of polynucleotides. The results of these modifications in intercalative complexes manifest themselves in the inhibition of numerous enzymatic reactions, dependent on the structures and topological forms of DNA and other polynucleotides. 2. ATP synthesis in mitochondria. Most of DNA-intercalators, including sanguinarine and ellipticine, belong to a group of penetrating (hydrophobic) cations, which are accumulated near the external side of inner mitochondrial membranes during the membrane energization. They neutralize negative charges, arising just as the inner mitochondrial membranes become energized. By this neutralization of membrane charges the ATP synthesis in inhibited and the oxidative phosphorylation renders to be uncoupled. All studied DNA-intercalators under certain conditions uncouple the mitochondrial oxidative phosphorylation. Apparent correlation between the agents' ability for DNA-intercalation and for mitochondrial ATP synthesis inhibition seems to be determined by the importance for both types of reactions of molecule hydrophobicity and positive charges. 3. Cholinesterase systems. Sanguinarine, ellipticine and some of their derivatives, like other DNA-intercalators studied, inhibit also the enzymatic activities of cholinesterase systems due to hydrophobicity and positive charges of their molecules. 4. Sanguinarine (and chelerythrine), are also capable of inhibiting the biological activity of SH-dependent enzymes and proteins. Due to the reactivity of iminium groups in sanguinarine and chelerythrine molecules with nucleophilic reagents, e.g. thiol groups of enzymes and other proteins, the activities of SH-enzymes and proteins are inhibited. In particular, sanguinarine and chelerythrine inhibit enzymatic activity of some SH-dependent ATPases, including membrane-bound cation-transport ATPases. The earlier accumulated experience of the application in medicine of plant saps and extracts containing these alkaloids, and of the treatment of many diseases (including benign and malignant tumors) by isolated alkaloids may be explained, to a certain extent, by the inhibition of activities of the above mentioned cellular targets. The selective toxicity of these alkaloids for the number of transformed cells can be explained in the same manner.

Effects of biologically active compounds bilirubin (BR, 0.1 and 0.2 mM), chelerythrine (CR, 0.1 and 0.5 mM) and farmorubicin (FR, 0.6 and 6.0 mM) on the phagosome-lysosome fusion (P-LF) were studied using fluorescent dye acridine orange for lysosomal labelling and yeast cells as a target. To investigate mechanisms of these effects, changes in fluidity of lysosomal membranes from murine liver were studied by measuring of fluorescence intensity, lifetime and polarization of the fluorescent membrane probes: DPH (1,6-diphenyl-1,3,5-hexatriene) and TMA-DPH [1-(4-triphenylamino)-6-phenyl-1,3,5-hexatriene] incorporated in isolated murine liver lysosomes. In order to characterize the induced cytoskeleton changes, the F-actin content in murine peritoneal macrophages was determined. It was found that all three compounds tested enhanced P-LF. Our results demonstrate that BR induces a decrease in DPH and TMA-DPH fluorescence polarization, FR increases DPH and TMA-DPH fluorescence polarization, and CR causes an increase in TMA-DPH fluorescence polarization in lysosomal membranes. All the three compounds increase F-actin content in peritoneal macrophages. Thus, the action of BR extended on P-LF is associated with increasing lysosomal membranes fluidity and cytoskeleton changes. The enhancement of P-LF under the action of FR and CR can be most likely explained by changes of cytoskeleton.

Processes of energy transduction were studied in isolated rat liver mitochondria, taken as a possible target for DNA intercalators, which differs from a usual one, associated with nucleic acid metabolism reactions. In the mitochondrial suspension, changes in respiration rates and latent ATPase activity in controlled state were defined in addition to a decrease in respiratory control index (V2/V1) and P/O ratio under the influence of DNA intercalators, benzophenanthridine alkaloid sanguinarine and acridine derivative APhMA. Within the range of examined sanguinarine and APhMA concentrations, the increase in respiration rate and activation of latent ATPase activity of mitochondrial suspension was first determined, with the maxima of these activities at 10(-4) M for both the agents. A further increase in sanguinarine and APhMA concentrations caused the inhibition of these reactions. Such dose-dependent shapes, with a maximum for the curves of mitochondrial respiration rate and ATPase activity "bell-shaped"), are typical for the majority of so far known uncouplers of oxidative phosphorylation in mitochondria. The fall of V2/V1 and P/O, under the influence of sanguinarine and APhMA, evidenced for the inhibition of ATP synthesis in mitochondria. The mechanism of uncoupling by sanguinarine and APhMA was supposed to differ from that by protonophores. It has been suggested that the uncoupling of oxidative phosphorylation by sanguinarine and APhMA was associated with the ability of these organic cations to neutralize negative charges near the external side of energized internal mitochondrial membranes. Correlation between the capacity for DNA intercalation and that for the energy transfer inhibition in mitochondria of these two agents is presumably based on the importance of positive charges and hydrophobic interactions, both for intercalation into polynucleotide double helices and for negative charges neutralization in energized mitochondrial membranes. Among DNA intercalators, so far examined, no agent has been established, which would not disturb the coupling of respiration and phosphorylation in mitochondria. However, there is no strong correlation for the agents between the ability to intercalate into DNA double helix and to disturb the energy transfer processes in mitochondria. Sanguinarine, which is more potent, as a DNA intercalator, than APhMA, is weaker than APhMA as an uncoupler of mitochondrial oxidative phosphorylation. For DNA-intercalation, the steric conformity between sizes of the intercalator molecule and of DNA base pairs is of great importance. On the other hand, for mitochondrial energy transfer disturbance, the agent ability to achieve sites of negative charges in the energized inner membranes is more significant.

It has been shown by electrophoresis that the earlier obtained thermoresistant sublines of the CHO-K1 cell line do not accumulate heat shock proteins when cultured at 37 degrees C. The thermostability of two lysosomal proteins--acid lipase and acid phosphatase--were higher in the thermoresistant cells than in the parental cells, whereas no differences in thermostability of galactosidase were found between heat resistant and parental lines. Thus, it is concluded that changes in the level of conformational flexibility of protein molecules may be one of the mechanisms of cell adaptation to growth at higher temperatures.

DNA intercalators include aromatic heterocyclic compounds of various chemical classes with profound biological activities. The flat molecules of these ligands intercalate between base pairs of DNA right-handed helix, lengthening and unwinding this structure at the intercalation sites. Lerman first postulated the intercalation model for complexes of native DNA with acridine derivatives. The structures of intercalative complexes were further confirmed by the X-ray diffraction method. Besides, other physico-chemical criteria of DNA intercalation are as following: the increase in the contour length of duplex DNA; unwinding of supercoils from natural supercoiled covalently closed duplex DNA; the increase in Tm of DNA in the complexes with ligands. The changes of spectral properties of bounded ligands are also observed for DNA-intercalating agents. Various experimental methods are based on changes in the properties of nucleic acid structures and ligands due to DNA intercalation, including the fluorescent determination of nucleic acid structures and quantities; fluorescent assays of activities of various enzymes involved in nucleic acid metabolism; chromosome identification according to their fluorescent banding patterns; separation of nucleic acid topological forms, and many other methods. The inhibition of reactions of DNA replication, transcription, topoisomerization and of enzymatic degradation by DNA intercalators represents an important consequence of DNA structure modification due to intercalation. Besides, as hydrophobic cations DNA intercalators uncouple the oxidative phosphorylation in mammalian cell mitochondria. There are some other protein and phospholipid targets for DNA-intercalators in vivo. The intracellular distribution of these agents appear to be a very complicated selective process. These data point to the importance of application of DNA intercalators in pharmacology.

Kinetics of sanguiritrine consumption by L cells of LSM substrain was studied in cell culture. About half of the drug used was absorbed by cells within 20 min. Sanguiritrine inhibited the lysosomal hydrolases (cathepsin D, beta-D-galactosidase and N-acetyl-beta-D-glucosaminidase) activity by 50% at concentration 2.10(-4) M. The drug a concentration 4.10(-4) M inhibited acid lipase by 55% and acid phosphatase by 58%.

Viral warts incidence and morbidity structure were analyzed basing on the records of consultations (a total of 30,518 subjects) and the results of purposeful check-ups of various patient populations (altogether 20,020 subjects) in the town of Tomsk. The incidence of viral warts was found to be much higher (12.94%) than it is acknowledged (2.82%). Age- and to a certain measure sex-specific predisposition to viral warts are known to exist. The condition is the most incident in subjects aged 20-29; in women the peak of the incidence is recorded in younger age than in men. Students rank first in the social structure of patients suffering from this condition, schoolchildren, second. Warts of the soles occur two times more frequently than vulgar warts. Children and adolescents more often have vulgar warts, particularly boys. Vulgar warts are the most incident in children aged 10-14, sole warts in those aged 20-29.

The fatty acid composition of the lipids synthesized de novo or during growth of the organism producing fusidic acid, Fusidium coccineum on complex media was studied. The content of the total extractable lipids in the mycelium did not exceed 10-11 per cent ty the biomass dry weight. Unsaturated fatty acids with 18 carbon atoms in the chain, mainly oleinic and linoleic acids and saturated fatty acids such as palmitic and stearic acids predominated. The ratio of the main fatty acids and the content of the minor acids were subject to strains and conditions of their cultivation. However, linoleic and oleinic acids predominated in all the lipids except the lipids from submerged cultures growing in the form of unusually large clots. Such lipids contained up to 60 per cent of palmitic acid.

The enzyme which catalyses template independent synthesis of polydeoxynucleotides from deoxynucleoside diphosphates was separated from E. coli DNA polymerase I by DEAE-cellulose chromatography followed by ultrafiltration through the M-50 Amicon filter. The ultrafiltration data indicate that the molecular weight of the enzyme is not higher than 50,000. The enzyme is not able to use deoxynucleoside triphosphates, ribonucleoside di- or triphosphates as substrates for the polymerization. The reaction of template independent polymerization proceeds with a lag period varying from 2 to 20 hours (for different preparations of enzyme) and is activated by Mg2+ (the optimal concentration 1-2 . 10(-3) M). The pH optimum of the reaction is at 8.5. The optimal concentration of deoxyribonucleoside diphosphates is 10(-3) M, and its increase strongly inhibits polymerization. The enzyme was supposed to be called deoxynucleoside diphosphate: olygonucleotide deoxynucleotidyltransferase (catalyzing polymerization without template). The presence of the enzyme in the preparations of E. coli DNA-polymerase I can explain the ability of the latter to catalyze the untemplated synthesis of poly dG : poly dC.

The increase of the contour length of the low molecular linear duplex DNA in the complex with an alkaloid sanguinarine has been evidenced by the viscometric method. The enzymatic hydrolysis of modified DNA by pancreatic deoxyribonuclease I and RNA synthesis of DNA by rat liver nuclear RNA polymerase were studied. Sanguinarine has been shown to inhibit the first stages of DNA hydrolysis. This alkaloid is a weaker inhibitor than ethidium bromide, a more potent inhibitor than actinomycin D and exerts an inhibiting effect similar to that of distamycin A. Sanguinarine also decreases the rate of the labelled precursor incorporation into the acid-insoluble fractions by nuclear RNA polymerase from rat liver. A 50% inhibition by sanguinarine was observed at the same alkaloid concentration as that of ethidium bromide.

Sanguinarine, a plant DNA-intercalator, is shown to inhibit the enzyme activity of the membrane-bound Ca2+-ATPase of rabbit skeletal muscle sarcoplasmic reticulum fragments. This inhibition could be interpreted by the well known ability of this alkaloid to interact with sulphydryl groups of the enzymes. Sanguinarine is a weaker inhibitor of this reaction than a sulphydryl group poison Ag+. The I50 is 3.10(-6) M for Ag+ and 7.10(-5) M for sanguinarine in the reaction medium with NO3- substituted for Cl-. In the standard reaction medium containing Cl-, the I50 for sanguinarine is 1.8.10(-4) M. In this case sanguinarine activates Ca2+-ATPase at low concentrations presumably because of uncoupling ATP hydrolysis from Ca2+ transport through membrane. Other agents studied are: DNA-intercalators--ethidium bromide, acriflavine, acridine orange; DNA-complexing antibiotics--actinomycin D, and olivomycin, alkaloids, quinine, morphine, berberine and an uncoupler of oxidative phosphorylation 2,4-dinitrophenol. These were found not to inhibit Ca2+-ATPase activity up to the concentrations of 10(-3)-10(-4) M.

The authors describe the treatment of 37 patients with condyloma acuminatum by an electron beam with a preset energy. The therapy has been highly effective. No complications or relapses have been recorded over a follow-up of 1.5-4 years.

The nature of the fine structure of the spores of fusidic acid-producing organism changed with an increase in the antibiotic activity of its strains. Impairments in the structure of the cell coating were observed. The surface layers of the spore wall became labile, they were capable of separating, destructive impairment in the electron solid structures were detected in the spore cytoplasm, such impairments resulted in autolysis of extended areas. The lability of the surface layers of the spore wall promoted contacts between the spore cell coatings. The increased adhesive properties of the spore coatings resulted in formation of the spore "heads" typical of sporulation in highly active strains. The latter were characterized by a marked increase in the number of the spores filled with lipids and devoid of the main cell organelles and having a changed structure of the spore wall. This explained the marked decrease in the viability of the conidia of the highly active strains of the organism producing fusidic acid.

The physiological and morphofunctional properties of the polyene-sensitive and resistant mutants of fungus producing fusidic acid were studied comparatively. The highly active nystatin resistant mutant was characterized by the decreased growth rates, lowered sporulation levels, retarded synthesis of nucleic acids and protein, lower respiration activity and higher mycelium lipid contents. The ultrastructural investigation of the polyene-resistant strain revealed the presence of lower numbers of ribosomes, membrane structures and mitochondria. Destructive changes in mitochondria and lipid masses in the hyphal cytoplasm were also observed.

The respiration of subline Leb-25 cells, resistant to ethidium bromide (EB, 25 g/ml), is 2.5 times slower than the respiration of parental L cells of mouse fibroblasts. The EB resistant cells have a normal level of ATP. Disturbances of mitochondrial functions can be observed such as a defect of the succinate dehydrogenase complex and the uncoupling of respiration and oxidative phosphorylation in mitochondria of Leb-25 cells.