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EN
N-Methyl-W-D-fructosyl amphotericin B methyl ester (MFAME) is a semisynthetic de­rivative of the antifungal antibiotic amphotericin B (AMB). In contrast to the parent antibiotic, the derivative is characterised by low toxicity to mammalian cells and good solubility in water of its salts. Comparative studies on biological properties of free MFAME, AMB and their liposomal formulations were performed. To obtain liposomal forms, the antibiotics were incorporated into small unilamellar vesicles composed of dimyristoyl phos- phatidylcholine (DMPC) and DMPC: cholesterol or ergosterol, 8:2 molar ratio. The effectivity of the liposomal and free forms of AMB and MFAME were compared by de­termination of fungistatic and fungicidal activity against Candida albicans ATCC 10261, potassium release from erythrocytes, and haemolysis. The results obtained indicate that in contrast to AMB, incorporation of MFAME into liposomes did not further improve its selective toxicity. Studies on the antagonistic effect of ergosterol and cholesterol on the antifungal ac­tivity of the antibiotics indicated that sterol interference was definitely less pro­nounced in the case of MFAME than in the case of AMB.
PL
Przedstawiono wyniki doświadczalnych badań procesu wzbogacania oleju rybnego w kwasy omega-3 metodą aminopropylowej ekstrakcji kolumnowej na złożu stałym. Najlepsze efekty uzyskano, gdy stosunek masy wolnych kwasów tłuszczowych do masy wypełnienia wynosił 1,5:100 i 3:100 (stężenie PUFA ok. 97%, EPA + DHA ok. 85%, odzysk ok. 90%). Kilkakrotne przepuszczenie oleju przez tę samą kolumienkę nie miało wpływu na stężenie kwasów EPA i DHA, natomiast znacznie zmniejszało zużycie jej wypełnienia. Efektywność procesu zatężania przy zastosowaniu metod ekstrakcji do fazy stałej i kompleksowania mocznikiem była zbliżona i wyższa niż efektywność przy zastosowaniu krystalizacji niskotemperaturowej.
EN
Polyunsatd. fatty acids contained in cod liver oil (initial conch. 39.04%) were concd. by extn. to solid phase (aminopropyl columns, acids-to-packing mass ratio 0.6:100 to 12:100), lowtemp. crystn. and complexation with urea to the final concn. 97.79%, 70.47% and 97.07%, resp. Docosahexaenoic and eicosapentaenoic acids were the main components of the concentrates. The no. of passings of the oil through the extn. column (up to 6) did not influence the conch. Efficiency.
EN
N3-(4-Methoxyfumaroyl)-L-2,3-diaminopropanoic acid (FMDP) and 2-amino-2- deoxy-D-glucitol-6-phosphate (ADGP) are strong inhibitors of the essential fungal en­zyme, glucosamine-6-phosphate synthase, but their antifungal activity is poor, due to slow penetration of these agents through the cytoplasmic membrane. In the present studies we have exploited the possibility of enhancement of ADGP and FMDP antifungal activity by improving their transport properties. It has been found that membrane-permeabilising polyene macrolides amphotericin B (AMB) and its .N-methyl-^-fructosyl methyl ester derivative (MF-AME), at subinhibitory concentra­tions, facilitate diffusion of ADGP through the fungal cell membrane, thus allowing a decrease of its minimal inhibitory concentration (MIC). Synergistic effects have been observed for combinations of ADGP with AMB or MF-AME. Fractional inhibitory con­centration (FIC) indexes, determined against a number of Candida spp., have been in the 0.18-0.81 range. Weak antifungal synergistic effects have been found for combi­nations of FMDP with AMB or MF-AME.ADGP can be easily encapsulated into unilamellar lipid vesicles. Liposomal preparations of ADGP demonstrated stronger antifungal activity against some fungal strains than free ADGP.
EN
N-Methyl-N-D-fructosyl-amphotericin B methyl ester (MFAME) is a new derivative of amphotericin B, which is characterised by low toxicity to mammalian cells and good solubility in water of its salts. The antifungal activity and effects of MFAME towards Candida albicans and Saccharomyces cerevisiae multidrug resistant MDR(+) and sensitive MDR(-) strains was compared with those of parent compound. The results obtained indicate that MDR(+) S. cerevisiae was sensitive to MFAME as well as to AMB. MFAME exhibited the same effects on fungal cells studied as parent antibiotic. The two antibiotics, depending on the dose applied induced cell stimulation, K+ efflux, and/or had a toxic effect.
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