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Biomedical subjects

L Ebringer

Publications and source records attributed to L Ebringer.

At least 37 records · Page 2Linked to original sources

[Successful modification of human intestinal microflora with oral administration of lactic acid bacteria].

Lactic acid bacteria in food can transiently colonize the intestine and exert health beneficial (probiotic) effects. These include: 1. Lactose digestion, improvement of diarrheal disorders (including traveller's diarrhea), prophylaxis of intestinal and urogenital infections--as a result of formation or reconstruction of a balanced indigenous microflora. 2. Inhibition of the mutagenicity of the intestinal contents and reduction of the incidence of intestinal tumours. 3. Immunomodulatory effects resulting in the improved host resistance. 4. Depression of the serum cholesterol level. The most of these effects were observed in a group of adult subjects administered daily by a lyophilized Enterococcus faecium M-74 in the form of waffles (Dr. Ebi) during nine weeks of a double blind placebo controlled clinical trial. The bacterium temporarily colonized the host intestine and its secretion in stool persisted for six weeks after the last dose. The mean activities of beta-D-glucuronidase in stools of subjects given waffles containing enterococci were reduced comparing to stools of placebo subjects. After six weeks of daily eating the waffles with enterococci, an increased production of superoxide and other reactive oxygen intermediates by peripheral neutrophils was observed. The increase corresponded in time with an elevated formation of IgG by peripheral blood mononuclear cells after polyclonal activation with mitogenes. Higher activities of myeloperoxidase and elastase in peripheral neutrophils were also ascertained during eating of waffles containing of E. faecium M-74. Hence, intake of E. faecium M-74 in the form of waffles may have an significant immunostimulatory effect on both phagocytosis performed by neutrophils and antibody production. (Tab. 6, Ref. 29.)

Administration, Oral↗

The effect of flavonoids on ofloxacin-induced mutagenicity in Euglena gracilis.

The antimutagenicity of 14 naturally occurring flavonoids (20 mumol/l) on ofloxacin (43 mumol/l and 86 mumol/l)-induced bleaching (mutagenicity) was studied in Euglena gracilis. The flavonoids chrysin, techtochrysin, chrysin-5-methylether galangin, galangin-5-methylether, pinocembrin and pinobanksin possess considerable antimutagenic properties against ofloxacin-induced bleaching of E. gracilis. Apigenin and isalpinin had only weak antimutagenic potency. Pinobanksin-5-methylether and pinobanksin-3-acetate showed very weak or no antimutagenic effect. However, kempferol, quercetin-3-methylether and quercetin-3,3'-dimethylether showed co-mutagenic or no antimutagenic effect depending on the concentration of ofloxacin. Two possible modes of action of the flavonoids on ofloxacin-induced bleaching of E. gracilis are discussed.

Animals↗

Biological activity of new aza analogues of quinolones.

A series of novel derivatives of 4H-pyrido[1,2-]pyrimidine, 1,4-dihydro-4-oxo-1,5-naphthyridine and 1,4-dihydro-4-oxo-1,6-naphthyridine were prepared and their biological activity was compared with that of nalidixic acid. The in vitro antibacterial activity of the tested compounds was lower than that of nalidixic acid except for two agents, 1b and 2c, with a higher activity against Enterococcus faecalis. The compounds were tested for their ability to cure four plasmids from two species of Enterobacteriaceae. The derivatives eliminated three plasmids (pKM101, pBR322, F'lac) at one-half or one-quarter of the minimal inhibitory concentration. Plasmid RP4 was unaffected by the treatment. None of these compounds showed better antichloroplast activity than nalidixic acid.

Animals↗

Influence of tetracyclines or cetylpyridinium bromide on activity of fluoroquinolones in Euglena gracilis.

To verify the hypothesis that the fluoroquinolone inhibitors of DNA gyrase generate some oxidant species and subsequently free radicals, the effects of simultaneous action of fluoroquinolones (ofloxacin, fleroxacin) and tetracyclines (tetracycline, doxycycline, thiatetracycline) or cetylpyridinium bromide as possible antioxidants on the flagellate Euglena gracilis were examined. Chloroplasts due to their bacterial character were injured and subsequently eliminated by fluoroquinolone. The loss of chloroplasts was accompanied by bleaching of originally green euglena cells. Tetracyclines, as well as cetylpyridinium bromide, decreased the euglena bleaching caused by ofloxacin or fleroxacin. The bleaching induced by ofloxacin or fleroxacin was most effectively inhibited by thiatetracycline and cetylpyridinium bromide. Control treating of cells with tetracyclines or cetylpyridinium bromide alone did not exert any bleaching effect. In vitro weak but significant interactions between examined substances were established as well.

Animals↗

Antimutagens reduce ofloxacin-induced bleaching in Euglena gracilis.

The genotoxic effect of ofloxacin was significantly decreased by standard antimutagens (sodium selenite, ascorbic acid, butylated hydroxyanisole and butylated hydroxytoluene) in the unicellular flagellate Euglena gracilis. The antiofloxacin activity of sodium selenite was also documented by a bacterial test in which the repair-proficient strain Salmonella typhimurium TA102 was used.

Animals↗

Tetracycline reduces fluoroquinolones-induced bleaching of Euglena gracilis.

Inhibitory activity of tetracycline against ofloxacin- and fleroxacin-induced bleaching of green and etiolated Euglena gracilis was examined. Tetracycline hydrochloride in concentrations of 83-2079 microM in the light partially inhibited the bleaching activity of 83 microM ofloxacin and of 162 microM fleroxacin. In the dark, the TC inhibition of the fluoroquinolones-induced bleaching activity was most obvious, the white colony counts were all decreased. The total inhibition of bleaching was observed in 43 microM ofloxacin and 81 microM fleroxacin both in light and darkness. Cell growth was not significantly influenced by ofloxacin, fleroxacin and tetracycline in the light or darkness. Cell growth was not significantly influenced by ofloxacin, fleroxacin and tetracycline in the light or darkness. Inhibition of ofloxacin-induced Euglena bleaching by tetracycline was more effective in etiolated cells. TC at 0-416 microM did not influence the growth of ofloxacin (2.15 microM)-induced Salmonella typhimurium revertants.

Animals↗

Hypocholesterolemic and immunostimulatory effects of orally applied Enterococcus faecium M-74 in man.

Lyophilized Enterococcus faecium M-74 was administered to 12 adult subjects in a daily oral dose of 5 x 10(9) bacteria for six weeks. The bacterium temporarily colonized the host intestine and its excretion with stool persisted for five weeks after the last does. The mean levels of serum cholesterol and LDL showed a a biphasic effect--an elevation followed by a sharp decrease (on day 64 of investigation). The decrease corresponded in time with a significant increase in the ability to reduce iodonitrotetrazolium and superoxide production by peripheral neutrophils incubated with zymosan or phorbol myristate acetate, and also with an elevated production of IgG by peripheral blood mononuclear cells. Hence, intake of E. faecium may have a hypocholesterolemic and immunostimulatory effect. It was also demonstrated that E. faecium significantly reduced the average activity of beta-D-glucuronidase in stools.

Adjuvants, Immunologic↗

Antimutagenicity in Euglena gracilis.

The genotoxic effect of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and furadantine (Fu) was significantly decreased by standard antimutagens (ascorbic acid, alpha-tocopherol, chlorophyllin and sodium selenite) in the unicellular flagellate Euglena gracilis. The effects of these compounds were verified also by a bacterial test in which three strains of Salmonella typhimurium, TA97, TA100, and TA102, were used. The above compounds were antimutagenic in strains of bacteria used, except for chlorophyllin which had no effect on strain TA102.

Animals↗

Elimination of plasmid pKM101 from Salmonella typhimurium by monoammonium salts.

The frequency of elimination of plasmid pKM101 from Salmonella typhimurium TA92 exposed to the action of 1-alkyl-1-ethylpiperidinium bromides and N-alkyl-N-[5-(benzoyloxy)-3-oxapentyl]-N,N-dimethylammonium bromides was non-linear in the homologous series. Change in the length of the alkyl chain markedly affected the elimination properties of the piperidine derivatives but had no effect on the elimination of benzoyl derivatives. Piperidines exhibited a weaker elimination capacity than the benzoyl derivatives. The most potent eliminator was the octylbenzoyl derivative, which causes the elimination of the plasmid in 80-85% cells.

Bromides↗

Influence of ofloxacin on chloroplasts and mitochondria in Euglena gracilis.

Ofloxacin (CAS 83380-47-6), a representative of new quinolones, which exerts inhibitory activity against DNA gyrase in bacteria, damages both semiautonomous organelles in Euglena gracilis: chloroplasts and partly mitochondria. The action of ofloxacin on these organelles was analysed by transmission electron microscopy. The first symptoms of ofloxacin treatment were mass aberrations of chloroplasts with subsequent diluting out of these pathological organelles from the cells, so giving rise to the heterotrophic mutants. The loss of chloroplasts is hereditary. Changes in ultrastructure of mitochondria were observed too. Cup-like (in sections ring-like) mitochondria represented the most frequent abnormalities of these organelles induced by the drug. After repeated subcultivations on ofloxacin-free media the number of damaged mitochondria gradually decreased to the normal.

Animals↗

Ofloxacin induces cytoplasmic respiration-deficient mutants in yeast Saccharomyces cerevisiae.

Ofloxacin, a new quinolone with potent antibacterial activity, was also found to be effective against yeast. At relatively high concentrations, and at mild alkaline pH, ofloxacin inhibited the growth of yeast cells in medium containing glucose, and prevented growth on glycerol, as carbon and energy source. The cells growing in the presence of ofloxacin exhibited abberrantly budded forms, lost their viability and many of them converted to cytoplasmic respiration-deficient mutants. Induction of mutants was also observed under non-growing conditions. The petite clones analysed exhibited suppressiveness and contained different fragments of the wild-type mitochondrial genome.

Cell Division↗

Elimination of plasmids pKM 101 and F'lac from Salmonella typhimurium and Escherichia coli by bisammonium salt. The effect of outer membrane pattern.

Plasmid-curing activity of N,N'-bis(decyldimethyl)-1,6-hexanediammonium dibromide, BDHD, was tested on six different plasmids in E. coli and plasmid pKM 101 in S. typhimurium. BDHD eliminated the F'lac plasmid from E. coli cells only with a low efficiency. Plasmid pKM 101 was eliminated from S. typhimurium cells significantly and this effect was dependent on an outer membrane pattern. A deep-rough mutant of S. typhimurium is completely resistant to curing activity of BDHD, while part-rough and smooth cells are susceptible to it. In contrast to pKM 101, a cryptic plasmid being present in S. typhimurium cells was not eliminated by BDHD. The curing activity of sodium dodecyl sulfate, acridine orange, crystal violet, and promethazine was also affected by the outer membrane pattern of S. typhimurium cells.

Cell Membrane↗

Interaction of drugs with extranuclear genetic elements and its consequences.

Bacterial ancestry of mitochondria and plastids is now generally accepted. Both organelles contain their own DNA and transcription-translation apparatus of a prokaryotic type. Due to this fact these systems carry bacteria-like properties. Thus organellar DNA and ribosomes are essentially different from nuclear DNA and cytoplasmic ribosomes in physical as well as in functional respects. Due to the bacterial character of both types of organelles they are susceptible to various antibacterial chemicals. Inhibitors of bacterial protein synthesis inhibit mitochondrial (plastidial) biogenesis. Therefore the cellular content of mitochondria (plastids)-made proteins decreases during cytoplasmic turnover or cell division in the presence of these drugs. Such drug activity consequently leads to a reduced capacity for oxidative phosphorylation or photosynthesis. Organellar genomes are less stable and more sensitive to mutagenesis as compared to nuclear genome. It means also that genotoxic agents induce various disorders of mitochondrial (plastidial) functions. Impairments in the respiratory chain are associated with structural as well as functional abnormalities of mitochondria. These are clinically expressed mostly in tissues with a high demand for ATP: brain, heart, skeletal muscle, and retina. On the other hand, some antibacterial inhibitors of mitochondrial biogenesis (e.g., tetracyclines) inhibit selectively tumor cell proliferation. Therefore they may be considered for use in anticancer therapy. The article summarizes the response of mitochondria and plastids in various organisms to drugs and environmental xenobiotics. Various model organisms suitable for detection of xenobiotic effect on mitochondria (plastids) are presented as well as the possible consequences of such interaction.

Animals↗

Different effect of hyperthermia and heat shock on the action of quinolone drugs versus some mutagens against chloroplasts of Euglena gracilis.

Hyperthermia (37 degrees C permanently) and heat shock (42 degrees C for 10 min, and then 27 degrees C) retarded the elimination of chloroplasts from the flagellate Euglena gracilis induced by quinolone antibacterial chemotherapeutics (OA, NA, Cnx, Ofx, Cpfx, Enx, Nfx) in comparison with their action at 27 degrees C. In the case of OA, NA, and Cnx those hyperthermic conditions completely blocked their action against chloroplasts. On the other hand, both temperature regimes accelerated the antichloroplast activity of the mutagens/carcinogens nitrosoguanidine and furylfuramide.

Animals↗

Injured mitochondria in cells of Euglena gracilis after DNA gyrase inhibitors treatment.

Five quinolone (ofloxacin, cinoxacin, enoxacin, ciprofloxacin, oxolinic acid) and one non-quinolone (coumermycin A1) inhibitors of prokaryotic DNA gyrase used in clinical practice for treatment of bacterial infections were experimentally examinated. As model organism the flagellate Euglena gracilis was used. Ultrastructural changes in chloroplasts and mitochondria caused by inhibitors were quantitavely evaluated. Simultaneously in all cases injury and hereditary loss of chloroplasts (bleaching) were observed in the cells. In some samples about 45% of cup-shaped mitochondria cumulated in the cytoplasm. In damaged mitochondria some degenerative signs were seen, but after the last subcultivation on drug-free media the number of injured mitochondria in the bleached cells yielded to the normal value.

4-Quinolones↗

Quinolones and coumarins eliminate chloroplasts from Euglena gracilis.

Quinolones and coumarins were potent eliminators of chloroplasts from Euglena gracilis. There was a remarkable similarity between antichloroplastic and antibacterial activities of DNA gyrase inhibitors. Quinolones produced 100% chloroplast-free cells in concentrations which do not affect cell viability. Optimal conditions were exponential growth, continuous illumination, and neutral or slightly alkaline pH. Coumarins were more toxic than quinolones. Among the quinolones, ofloxacin was the most potent in eliminating chloroplasts. Among the coumarins, coumermycin A1 was the most potent. New quinolones and coumermycin A1 were able to induce the complete inability of originally green cells to form green colonies after 24 h of drug exposure, while clorobiocin and novobiocin required several days of exposure. Darkness, heat shock (42 degrees C, 10 min), or simultaneous treatment with chloramphenicol or rifampin decreased the potency of DNA gyrase inhibitors for producing chloroplast-free cells. Remarkably, in cells in which division was blocked by three different methods (resting medium, hyperthermic conditions [37 degrees C], or addition of cycloheximide), new quinolones and coumermycin A1 nevertheless eliminated chloroplasts. The antichloroplastic activity of DNA gyrase inhibitors is additional data suggesting an evolutionary relationship between chloroplasts and eubacteria.

4-Quinolones↗