Sideropenie a sideropenní anémie postihují nejméně polovinu pacientů trpících Crohnovou nemocí a ulcerózní kolitidou. Adekvátní substituce perorálním železem je součástí všeobecně akceptovaných doporučení u těchto nemocných. Nesnášenlivost a výskyt nežádoucích účinků při substituci perorálními preparáty obsahujícími anorganické železo je u nemocných s idiopatickými střevními záněty (IBD – inflammatory bowel disease) relativně častá. Metodika a výsledky: Soubor 43 pacientů s IBD ve fázi remise, trpících sideropenií (feritin < 30 µg/l) nebo lehkou sideropenní anémií (Hb 100–120, resp. 130 g/l). Pacienti užívali GlobiFer®forte s obsahem hemového i minerálního železa po dobu 12 týdnů. Medián koncentrace hemoglobinu se signifikantně zvýšil v porovnání s výchozí hodnotou 123,5 g/l v týdnu 0 na 133,5 g/l v týdnu 12 (p = 0,004) a medián středního objemu erytrocytu se zvýšil z 85,2 fL v týdnu 0 na 87,3 fL v týdnu 12 (p = 0,05). Výskyt mírných nežádoucích účinků byl zaznamenán pouze u jediného pacienta. Závěr: Hemové železo v preparátu GlobiFer®forte je velmi dobře snášeno IBD pacienty a vede k úpravě sideropenie nebo lehké sideropenní anémie.
Introduction: Sideropenia and sideropenic anemia occurring in more than a half of patients suffering from inflammatory bowel disease (IBD). The efficacy in replenishing of the iron storage or therapy of sideropenic anemia is part of the national guidelines for IBD population. Unfortunately, in IBD patients, therapy with inorganic iron preparations is associated with intolerance or side effects which occurred relatively often. Methods and results: A cohort of 43 IBD patients without inflammatory activity (31 with Crohn's disease and 12 with ulcerative colitis) with sideropenia (ferritin level < 30 µg /L) or mild sideropenic anemia (hemoglobin 100 g/L - 120 g/L) were recruited for 12 weeks therapy with GlobiFer® forte tablet containing heme iron and also inorganic iron. The median hemoglobin concentration significantly increased from week 0 to week 12 (123.5 g/L to 133.5 g/L) (P = 0.004) and median mean red cell corpuscular volume changed from 85.2 fL at week 0 to 87.3 fL at week 12 (P = 0.05). GlobiFer®forte was very well tolerated and side effects occurred only in one patient. Conclusion: The heme iron which is part of GlobiFer®forte was very well tolerated and this therapy led to the normalization of hemoglobin concentration and mean red cell volume at the end of the therapy.
- Klíčová slova
- GlobiFer forte,
- MeSH
- anemie z nedostatku železa farmakoterapie MeSH
- dietní železo aplikace a dávkování farmakologie metabolismus MeSH
- lidé MeSH
- potravní doplňky MeSH
- těhotenství MeSH
- železnaté sloučeniny farmakologie metabolismus MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- novinové články MeSH
OBJECTIVES: Cytochromes P450 (CYPs) are heme enzymes oxygenating a broad range of substrates. Their activity is dependent on the presence of a suitable electron donor (eukaryotic NADPH:CYP oxidoreductase or cytochrome b5). The Escherichia naturally contain no CYPs and no NADPH:CYP oxidoreductase, however it was reported that some CYPs heterologously expressed in E. coli may exist in the ferrous form. A small bacterial flavoprotein, flavodoxin is considered to be responsible for reduction some of these CYPs. METHODS: The reduction state of several human CYPs expressed in the intact living E. coli cells was examined. In addition, molecular dynamics and steered molecular dynamics simulations were performed to predict and compare affinity of flavodoxin toward selected CYPs. RESULTS: We determined the reduction state of five human CYPs heterologously expressed in E. coli. The computationally predicted stabilities of CYP-flavodoxin complexes correlate with the percentage of reduced CYPs in bacterial cells. The mean electron transfer distance within optimized complexes was also related to the percentage of reduced CYPs. CONCLUSION: Depending on the resting state, the CYPs heterologously expressed in E. coli could be divided into two groups; CYP2C8, 2C9, 3A4 are in E. coli present mainly in the oxidized form; while CYP1A1, 1A2, 2A6, 2A13, 2B6, 2D6 are found predominantly in the reduced form. We found a significant correlation between the stability of CYP-flavodoxin complexes and the percentage of reduced CYPs in bacteria. Hence, the naturally expressed flavodoxin is probably responsible for reduction of a larger group of human CYPs in bacterial cells.
- MeSH
- aromatické hydroxylasy metabolismus MeSH
- cytochrom P-450 CYP1A1 metabolismus MeSH
- cytochrom P-450 CYP1A2 metabolismus MeSH
- cytochrom P-450 CYP2D6 metabolismus MeSH
- cytochrom P-450 CYP3A metabolismus MeSH
- cytochrom P450 CYP2A6 metabolismus MeSH
- cytochrom P450 CYP2B6 metabolismus MeSH
- cytochrom P450 CYP2C8 metabolismus MeSH
- cytochrom P450 CYP2C9 metabolismus MeSH
- Escherichia coli MeSH
- flavodoxin metabolismus MeSH
- geneticky modifikované organismy MeSH
- lidé MeSH
- NADPH-cytochrom c-reduktasa metabolismus MeSH
- oxidace-redukce MeSH
- systém (enzymů) cytochromů P-450 metabolismus MeSH
- železité sloučeniny metabolismus MeSH
- železnaté sloučeniny metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
In contrast to iron-oxidizing Acidithiobacillus ferrooxidans, A. ferrooxidans from a stationary phase elemental sulfur-oxidizing culture exhibited a lag phase in pyrite oxidation, which is similar to its behaviour during ferrous iron oxidation. The ability of elemental sulfur-oxidizing A. ferrooxidans to immediately oxidize ferrous iron or pyrite without a lag phase was only observed in bacteria obtained from growing cultures with elemental sulfur. However, these cultures that shifted to ferrous iron oxidation showed a low rate of ferrous iron oxidation while no growth was observed. Two-dimensional gel electrophoresis was used for a quantitative proteomic analysis of the adaptation process when bacteria were switched from elemental sulfur to ferrous iron. A comparison of total cell lysates revealed 39 proteins whose increase or decrease in abundance was related to this phenotypic switching. However, only a few proteins were closely related to iron and sulfur metabolism. Reverse-transcription quantitative PCR was used to further characterize the bacterial adaptation process. The expression profiles of selected genes primarily involved in the ferrous iron oxidation indicated that phenotypic switching is a complex process that includes the activation of genes encoding a membrane protein, maturation proteins, electron transport proteins and their regulators.
- MeSH
- 2D gelová elektroforéza MeSH
- Acidithiobacillus růst a vývoj metabolismus fyziologie MeSH
- bakteriální proteiny biosyntéza MeSH
- fyziologická adaptace MeSH
- genetická transkripce MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- metabolické sítě a dráhy genetika MeSH
- oxidace-redukce MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- proteom analýza MeSH
- regulace genové exprese * MeSH
- síra metabolismus MeSH
- stanovení celkové genové exprese MeSH
- sulfidy metabolismus MeSH
- železnaté sloučeniny metabolismus MeSH
- železo metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The bloodstream form of Trypanosoma brucei acquires iron from transferrin by receptor-mediated endocytosis. However, it is unknown how procyclic forms that cannot bind transferrin acquire iron. Here, we show that the procyclic form of T. brucei efficiently takes up iron from ferric complexes via a reductive mechanism and that iron obtained using this mechanism is transported to, and used in, the mitochondria. The affinity of the transport system is comparable to that of Saccharomyces cerevisiae , with an apparent K(m) of 0.85 μM.
- MeSH
- elektroforéza v polyakrylamidovém gelu MeSH
- FMN-reduktasa metabolismus MeSH
- interakce hostitele a parazita MeSH
- mitochondrie metabolismus MeSH
- oxidace-redukce MeSH
- Trypanosoma brucei brucei metabolismus MeSH
- železité sloučeniny metabolismus MeSH
- železnaté sloučeniny metabolismus MeSH
- železo metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The conventional stoichiometry of the oxidation of elemental sulfur by ferric iron in Acidithiobacillus ferrooxidans was not in agreement with our experimental data in terms of ferrous iron and proton formation. Reaction modelling under the actual conditions of bacterial activity resulted in a different stoichiometry, where additional iron species participate in the process to affect the number of released protons. The suggested reaction equation may more accurately predict the intensity of environmental acidification during the anaerobic bioprocess.
- MeSH
- Acidithiobacillus metabolismus MeSH
- anaerobióza MeSH
- energetický metabolismus MeSH
- oxidace-redukce MeSH
- síra metabolismus MeSH
- železité sloučeniny metabolismus MeSH
- železnaté sloučeniny metabolismus MeSH
- železo metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Elemental sulfur oxidation by ferric iron in Acidithiobacillus ferrooxidans was investigated. The apparent Michaelis constant for ferric iron was 18.6 mM. An absence of anaerobic ferric iron reduction ability was observed in bacteria maintained on elemental sulfur for an extended period of time. Upon transition from ferrous iron to elemental sulfur medium, the cells exhibited similar kinetic characteristics of ferric iron reduction under anaerobic conditions to those of cells that were originally maintained on ferrous iron. Nevertheless, a total loss of anaerobic ferric iron reduction ability after the sixth passage in elemental sulfur medium was demonstrated. The first proteomic screening of total cell lysates of anaerobically incubated bacteria resulted in the detection of 1599 protein spots in the master two-dimensional electrophoresis gel. A set of 59 more abundant and 49 less abundant protein spots that changed their protein abundances in an anaerobiosis-dependent manner was identified and compared to iron- and sulfur-grown cells, respectively. Proteomic analysis detected a significant increase in abundance under anoxic conditions of electron transporters, such as rusticyanin and cytochrome c(552), involved in the ferrous iron oxidation pathway. Therefore we suggest the incorporation of rus-operon encoded proteins in the anaerobic respiration pathway. Two sulfur metabolism proteins were identified, pyridine nucleotide-disulfide oxidoreductase and sulfide-quinone reductase. The important transcription regulator, ferric uptake regulation protein, was anaerobically more abundant. The anaerobic expression of several proteins involved in cell envelope formation indicated a gradual adaptation to elemental sulfur oxidation.
- MeSH
- 2D gelová elektroforéza MeSH
- Acidithiobacillus metabolismus MeSH
- anaerobióza MeSH
- bakteriální proteiny analýza MeSH
- fyziologická adaptace MeSH
- kinetika MeSH
- oxidace-redukce MeSH
- proteomika MeSH
- síra metabolismus MeSH
- tandemová hmotnostní spektrometrie MeSH
- železité sloučeniny metabolismus MeSH
- železnaté sloučeniny metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Klíčová slova
- deficit glukoso-6-fosfát dehydrogenázy, pulsní symetrie, chloritan sodný,
- MeSH
- diagnostické techniky a postupy MeSH
- dospělí MeSH
- hemoglobiny genetika metabolismus MeSH
- hemolýza genetika účinky léků MeSH
- klinický obraz nemoci MeSH
- lidé MeSH
- methemoglobinemie diagnóza etiologie terapie MeSH
- nedostatek glukóza-6-fosfátdehydrogenázy metabolismus MeSH
- oxymetrie metody využití MeSH
- poruchy metabolismu železa etiologie komplikace MeSH
- sloučeniny chloru metabolismus škodlivé účinky MeSH
- urgentní zdravotnické služby využití MeSH
- železité sloučeniny metabolismus škodlivé účinky MeSH
- železnaté sloučeniny metabolismus škodlivé účinky MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
The effect of illumination and molecular oxygen on the redox and the redox potential changes of cytochrome b(559) (cyt b(559)) has been studied in Tris-treated spinach photosystem II (PSII) membranes. It has been demonstrated that the illumination of Tris-treated PSII membranes induced the conversion of the intermediate-potential (IP) to the reduced high-potential (HP(Fe2+)) form of cyt b(559), whereas the removal of molecular oxygen resulted in the conversion of the IP form to the oxidized high-potential (HP(Fe3+)) form of cyt b(559). Light-induced conversion of cyt b(559) from the IP to the HP form was completely inhibited above pH 8 or by the modification of histidine ligand that prevents its protonation. Interestingly, no effect of high pH or histidine modification was observed during the conversion of the IP to the HP form of cyt b(559) after the removal of molecular oxygen. These results indicate that conversion from the IP to the HP form of cyt b(559) proceeds via different mechanisms. Under illumination, conversion of the IP to the HP form of cyt b(559) depends primarily on the protonation of the histidine residue, whereas under anaerobic conditions, the conversion of the IP to the HP form of cyt b(559) is driven by higher hydrophobicity of the environment around the heme iron resulting from the absence of molecular oxygen.
- MeSH
- chemické modely MeSH
- cytochromy typu b chemie metabolismus MeSH
- fotosystém II - proteinový komplex chemie metabolismus MeSH
- histidin chemie metabolismus MeSH
- koncentrace vodíkových iontů MeSH
- kyslík metabolismus farmakologie MeSH
- oxidace-redukce účinky léků účinky záření MeSH
- potenciometrie MeSH
- rostlinné proteiny chemie metabolismus MeSH
- spektrofotometrie MeSH
- Spinacia oleracea metabolismus MeSH
- světlo MeSH
- tromethamin chemie farmakologie MeSH
- tylakoidy účinky léků metabolismus účinky záření MeSH
- železité sloučeniny chemie metabolismus MeSH
- železnaté sloučeniny chemie metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
