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[Effect of prodigiozan on the course of candidiasis of the oral mucosa clinically and in an experiment].

The effect of various doses of prodigiozan on Candida infection was studied under experimental and clinical conditions. Hamsters and guinea pigs were used in the experiments. Prodigiozan was administered intramuscularly to the hamsters in doses of 100 gamma/kg of the body weight 1 hour before the infection and intracutaneously to the guinea pigs in doses of 50 gamma/kg 2 days before the infection. The results showed that the drug accelerated the recovery of the animals. In complex therapy of a group of 22 patients with candidosis of the mouth mucosa of various localization prodigiozan was administered thrice in doses of 50 gamma/kg. This provided faster elimination of the pathological process.

Animals↗

[Effect of several antibiotics and their combination with prodigiozan on Y. pestis EV, engulfed by macrophages].

The effect of various antibiotics, such as streptomycin, gentamicin, ampicillin, benzylpenicillin, tetracycline, chlortetracycline and levomycetin on the plague bacteria (strain Y. pestis EV) located inside the cells was studied. Peritoneal macrophages of albino mice with aceptic inflammation of the abdominal cavity caused by intraperitoneal administration of 2 ml of sterile meat-peptone broth were used in the experiments. The ratio of the macrophages and microbes was 1 : 50. A part of the mice were treated with prodigiozan 24 hours before taking the exudate. The preparations of the macrophages of albino mice with the microbes absorbed by them served as the control. The effect of the antibiotics and their combinations with prodigiozan was stimated by the coefficient of multiplication suppression against the control. The observations were made in dynamics. The studies showed that the macrophage activity of the mice treated with prodigiozan after exposure to the antibiotics was reliably higher than that in the control and digestion of the microbes located inside the cells started earlier, providing more complete phagocytosis.

Ampicillin↗

Characterization of the new immunosuppressive drug undecylprodigiosin in human lymphocytes: retinoblastoma protein, cyclin-dependent kinase-2, and cyclin-dependent kinase-4 as molecular targets.

Undecylprodigiosin (UP) is the first described member of a family of related compounds showing immunosuppressive activity. We have investigated the biological effect and mechanism of action of UP in human lymphocytes. We show that UP blocks the proliferation of purified peripheral human T and B lymphocytes with an IC50 of 3 to 8 ng/ml and following stimulation by all mitogens used, with no effect on cell death. At the concentrations active on fresh lymphocytes, UP has no significant effect on the proliferation of different leukemic cell lines. UP blocks T cell activation in mid to late G1 phase and before entry into S phase, as shown by analysis of the cell cycle and of the expression of c-myc, IL-2, transferrin receptor, and B-myb. UP inhibits only partially the expression of IL-2R, suggesting that the major target of UP is localized downstream from the interaction between IL-2 and its receptor. The expression of cell cycle genes was investigated. The phosphorylation of the retinoblastoma protein was completely blocked by UP, an event alone sufficient to explain the block of S phase entry and the inhibition of proliferation. The induction of cyclin D2 and the decrease in p27 were not inhibited by UP, whereas the induction of cyclin E, cyclin A, cyclin-dependent kinase-2, and cyclin-dependent kinase-4 was strongly inhibited, potentially explaining the inhibition of retinoblastoma protein phosphorylation. These data clearly show that the site of action of UP is different from that of both cyclosporin A and rapamycin, and that this new class of compounds may, therefore, be good candidates for combined therapy.

CDC2-CDC28 Kinases↗