Lincomycin
Dotaz
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- MeSH
- infekce chirurgické rány farmakoterapie MeSH
- lidé MeSH
- linkomycin terapeutické užití MeSH
- Check Tag
- lidé MeSH
- MeSH
- antiinfekční látky farmakologie terapeutické užití MeSH
- antiprotozoální látky farmakologie terapeutické užití MeSH
- Eukaryota účinky léků MeSH
- finanční podpora výzkumu jako téma MeSH
- gramnegativní bakterie účinky léků MeSH
- grampozitivní bakterie účinky léků MeSH
- klindamycin farmakologie MeSH
- lidé MeSH
- linkomycin farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
In vitro byla sledována dynamika uvolňování neomycinu a linkomycinu ze sklokeramických materiálů BAS-0, BAS-HA a BAS-R ve formě drti. Po nasycení jednotlivými antibiotiky byly vzorky sklokeramiky převrstveny fibrinovým lepidlem a po jeho zatuhnutí pufrovaným fyziologickým roztokem. Ve vzorcích odebíraných ve stanovených intervalech po dobu 2 měsíců bylo stanoveno eluované množství ATB agarovou jamkovou metodou. Vylučování ATB ze sklokeramiky probíhalo ve 2 fázích, k zpomalení eluce docházelo většinou po 6 hodinách. Pri použiti kompožit došlo k dalšímu snížení rychlosti eluce ještě po 48 hodinách. Z celkového vyloučeného množství ATB bylo 50 % uvolněno u neomycinu za 2-4 hodiny, u linkomycinu za 6 hodin. Po 48 hodinách byla uvolňována už jen malá množství ATB, která však byla detekovatelná ještě i na konci sledovaného období. Celkové uvolněné množství ATB bylo ovlivněno typem použitého materiálu, event. v menší míře i jeho velikostí a v případě kompozit vzájemným poměrem jejich složek.
The dynamics of release of neomycin and lincomycin from glass-ceramľc materials BAS-0, BAS-HA ind BAS-R in the form of cullet was monitored in vitro. After the saturation by individual antibiotics the glass-ceramic samples were overlaid with fibrin glue and after it became solid they were covered with buffered physiological solution. In the samples taken at planned intervals in the course of 2 months eluted ATB quantity was determined by agar well method. Release of ATB from glass-ceramics proceeded in two phases, elution slowed down in most cases after 6 hours. With the use of composites there occurred another slowing down of the speed of elution after another 48 hours. Of the total eluted quantity of ATB 50 % was released in neomycine in 2-4 hours, in lincomycin in 6 hours. After 48 hours only small quantities of ATB were eluted, however, they were still detected at the end of the monitored period.The total released quantity of ATB was influenced by the type of the material used, or to a lesser extent, also by size of its particules and in case of composites by the proportion of their components.
- MeSH
- adheziva MeSH
- biokompatibilní materiály MeSH
- lidé MeSH
- linkomycin farmakokinetika terapeutické užití MeSH
- neomycin farmakokinetika terapeutické užití MeSH
- nosiče léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- srovnávací studie MeSH
The gene lmbB2 of the lincomycin biosynthetic gene cluster of Streptomyces lincolnensis ATCC 25466 was shown to code for an unusual tyrosine hydroxylating enzyme involved in the biosynthetic pathway of this clinically important antibiotic. LmbB2 was expressed in Escherichia coli, purified near to homogeneity and shown to convert tyrosine to 3,4-dihydroxyphenylalanine (DOPA). In contrast to the well-known tyrosine hydroxylases (EC 1.14.16.2) and tyrosinases (EC 1.14.18.1), LmbB2 was identified as a heme protein. Mass spectrometry and Soret band-excited Raman spectroscopy of LmbB2 showed that LmbB2 contains heme b as prosthetic group. The CO-reduced differential absorption spectra of LmbB2 showed that the coordination of Fe was different from that of cytochrome P450 enzymes. LmbB2 exhibits sequence similarity to Orf13 of the anthramycin biosynthetic gene cluster, which has recently been classified as a heme peroxidase. Tyrosine hydroxylating activity of LmbB2 yielding DOPA in the presence of (6R)-5,6,7,8-tetrahydro-L-biopterin (BH4) was also observed. Reaction mechanism of this unique heme peroxidases family is discussed. Also, tyrosine hydroxylation was confirmed as the first step of the amino acid branch of the lincomycin biosynthesis.
- MeSH
- antibakteriální látky biosyntéza MeSH
- bakteriální proteiny genetika metabolismus MeSH
- cirkulární dichroismus MeSH
- dihydroxyfenylalanin metabolismus MeSH
- Escherichia coli enzymologie genetika MeSH
- exprese genu MeSH
- hem chemie metabolismus MeSH
- hemoproteiny genetika metabolismus MeSH
- hydroxylace MeSH
- linkomycin biosyntéza MeSH
- multigenová rodina MeSH
- rekombinantní proteiny genetika metabolismus MeSH
- Streptomyces enzymologie genetika MeSH
- tyrosin-3-monooxygenasa genetika metabolismus MeSH
- tyrosin metabolismus MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- železo chemie metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The lincomycin biosynthetic gene lmbX was deleted in Streptomyces lincolnensis ATCC 25466, and deletion of this gene led to abolition of lincomycin production. The results of complementation experiments proved the blockage in the biosynthesis of lincomycin precursor 4-propyl-L-proline. Feeding this mutant strain with precursor derivatives resulted in production of 4'-butyl-4'-depropyllincomycin and 4'-pentyl-4'-depropyllincomycin in high titers and without lincomycin contamination. Moreover, 4'-pentyl-4'-depropyllincomycin was found to be more active than lincomycin against clinical Staphylococcus isolates with genes determining low-level lincosamide resistance.
- MeSH
- antibakteriální látky farmakologie chemie metabolismus MeSH
- bakteriální proteiny genetika metabolismus MeSH
- lidé MeSH
- linkomycin analogy a deriváty farmakologie chemie metabolismus MeSH
- mikrobiální testy citlivosti MeSH
- molekulární struktura MeSH
- prolin analogy a deriváty metabolismus MeSH
- stafylokokové infekce mikrobiologie MeSH
- Staphylococcus účinky léků MeSH
- Streptomyces genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
The biosynthetic pathway of the clinically important antibiotic lincomycin is not known in details. The precise knowledge of the lincomycin biosynthesis is a prerequisite for generation of improved derivatives by means of combinatorial genetics. Methods allowing determination of the key intermediates are very important tools of the pathway investigation. Two new high-performance liquid chromatography methods with fluorescence detection for determination of lincomycin precursors in fermentation broth of Streptomyces lincolnensis and its lincomycin nonproducing mutants were developed. The first one enables simultaneous analysis of methylthiolincosamide (MTL) and N-demethyllincomycin (NDL), whereas the second one is suitable for 4-propyl-L-proline (PPL) assay. Both methods are based on the pre-column derivatization: MTL and NDL with 4-chloro-7-nitrobenzofurazan; PPL with o-phthaldialdehyde. The methods were validated with lower limit of quantification values of 2.50, 3.75, and 3.75 microg ml(-1) for MTL, NDL, and PPL, respectively. The inter- and intra-day accuracies and precisions were all within 12%. Stability of oxidized and derivatized analytes was investigated.
- MeSH
- amidy analýza MeSH
- fermentace MeSH
- financování organizované MeSH
- fluorescence MeSH
- linkomycin analogy a deriváty biosyntéza MeSH
- molekulární struktura MeSH
- prolin analogy a deriváty analýza MeSH
- reprodukovatelnost výsledků MeSH
- Streptomyces metabolismus MeSH
- sulfhydrylové sloučeniny analýza MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
