Untargeted metabolite profiling using high-resolution mass spectrometry coupled with liquid chromatography (LC-HRMS), followed by data analysis with the Compound Discoverer 2.0™ software, was used to study the metabolism of imatinib in humans with chronic myeloid leukemia. Plasma samples from control (drug-free) and patient (treated with imatinib) groups were analyzed in full-scan mode and the unknown ions occurring only in the patient group were then, as potential imatinib metabolites, subjected to multi-stage fragmentation in order to elucidate their structure. The application of an untargeted approach, as described in this study, enabled the detection of 24 novel structurally unexpected metabolites. Several sulphur-containing compounds, probably originating after the reaction of reactive intermediates of imatinib with endogenous glutathione, were found and annotated as cysteine and cystine adducts. In the proposed mechanism, the cysteine adducts were formed after the rearrangement of piperazine moiety to imidazoline. On the contrary, in vivo S-N exchange occurred in the case of the cystine adducts. In addition, N-O exchange was observed in the collision cell in the course of the fragmentation of the cystine adducts. The presence of sulphur in the cysteine and cystine conjugates was proved by means of ultra-high resolution measurements using Orbitrap Elite. The detection of metabolites derived from glutathione might improve knowledge about the disposition of imatinib towards bioactivation and help to improve understanding of the mechanism of its hepatotoxicity or nephrotoxicity in humans.
- MeSH
- antitumorózní látky krev metabolismus moč MeSH
- chromatografie kapalinová MeSH
- cystein metabolismus MeSH
- cystin metabolismus MeSH
- imatinib mesylát krev metabolismus moč MeSH
- inhibitory proteinkinas krev metabolismus moč MeSH
- lidé MeSH
- síra krev metabolismus moč MeSH
- tandemová hmotnostní spektrometrie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- citráty terapeutické užití MeSH
- cystin genetika metabolismus škodlivé účinky MeSH
- cystinurie * genetika moč patofyziologie MeSH
- dítě MeSH
- lidé MeSH
- mikrocefalie MeSH
- pití MeSH
- poruchy růstu MeSH
- svalová hypotonie MeSH
- urolitiáza epidemiologie etiologie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
A model small-scale field experiment was set up to investigate selenium (Se) uptake by four different varieties of broccoli plants, as well as the effect of Se foliar application on the uptake of essential elements for plants calcium (Ca), copper (Cu), iron (Fe), potassium (K), magnesium (Mg), manganese (Mn), phosphorus (P), sulfur (S), and zinc (Zn). Foliar application of sodium selenate (Na2SeO4) was carried out at two rates (25 and 50 g Se/ha), and an untreated control variant was included. Analyses of individual parts of broccoli were performed, whereby it was found that Se in the plant accumulates mainly in the flower heads and slightly less in the leaves, stems, and roots, regardless of the Se rate and broccoli variety. In most cases, there was a statistically significant increase of Se content in all parts of the plant, while there was no confirmed systematic influence of the addition of Se on the changing intake of other monitored elements. Selenization of broccoli leads to an effective increase in the Se content at a rate of 25 g/ha, whereas the higher rate did not result in a substantial increase of Se content compared to the lower rate in all varieties. Therefore, the rate of 25 g/ha can be recommended as effective to produce broccoli with an increased Se content suitable for consumption. Moreover, Se application resulted in an adequate increase of the main organic compounds of Se, such as selenocystine (SeCys2), selenomethionine (SeMet), and Se-methylselenocysteine (Se-MeSeCys).
- MeSH
- biologický transport MeSH
- Brassica účinky léků metabolismus MeSH
- cystin analogy a deriváty izolace a purifikace metabolismus MeSH
- kationty dvojmocné metabolismus MeSH
- kationty jednomocné metabolismus MeSH
- kořeny rostlin účinky léků metabolismus MeSH
- květy účinky léků metabolismus MeSH
- listy rostlin účinky léků metabolismus MeSH
- organoselenové sloučeniny izolace a purifikace metabolismus MeSH
- selenocystein analogy a deriváty izolace a purifikace metabolismus MeSH
- selenomethionin izolace a purifikace metabolismus MeSH
- sloučeniny selenu izolace a purifikace metabolismus farmakologie MeSH
- spektrofotometrie atomová MeSH
- stonky rostlin účinky léků metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Článek pojednává o současných trendech metafylaxe urolitiázy, laboratorních vyšetřeních krve a moči určených k prevenci recidivy močových kamenů. Podrobněji jsou rozebrány dietní a léková opatření (obecná a specifická), jakožto i nejčastější metabolické poruchy spojené s tvorbou jednotlivých typů konkrementů.
The article deals with the current trends in the metaphylaxis of urolithiasis and laboratory blood and urine tests intended to prevent the recurrence of urinary stones. Dietary and medical measures (general and specific) as well as the most common metabolic disorders associated with the formation of particular types of concrements are discussed in more detail.
- MeSH
- antibakteriální látky terapeutické užití MeSH
- citráty terapeutické užití MeSH
- cystin metabolismus škodlivé účinky účinky léků MeSH
- dietoterapie metody využití MeSH
- farmakoterapie * metody využití MeSH
- hyperkalciurie etiologie prevence a kontrola terapie MeSH
- hyperoxalurie etiologie prevence a kontrola terapie MeSH
- kaménky diagnóza etiologie terapie MeSH
- kaptopril terapeutické užití MeSH
- klinické laboratorní techniky metody využití MeSH
- kyselina močová izolace a purifikace MeSH
- lidé MeSH
- metabolické nemoci diagnóza etiologie terapie MeSH
- methionin terapeutické užití MeSH
- močové kameny diagnóza etiologie terapie MeSH
- oxaláty MeSH
- urolitiáza * diagnóza prevence a kontrola terapie MeSH
- urologické chirurgické výkony * metody využití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Cysteine dioxygenase (CDO) is involved in regulation of intracellular cysteine levels by catabolising the cysteine to sulphite and sulphate. In keratinolytic fungi, sulphite is actively excreted to reduce disulphide bridges in keratin before its enzymatic degradation. The pathogenicity role of CDO was confirmed in cysteine-hypersensitive and growth-defective ΔCdo mutant of Arthroderma benhamiae on hair and nails. We analysed the CDO expression regulation in T. mentagrophytes (anamorph of A. benhamiae) mycelia by determining the Cdo mRNA and CDO protein levels and by analysing the proportion of two molecular forms of CDO in response to l-cystine exposure. Cdo mRNA levels in mycelia lysates were detected by reverse-transcription real-time polymerase chain reaction and CDO protein by western blot using mouse CDO-specific hyperimmune serum. The Cdo mRNA level increased gradually 2.5-4.5 h after exposure of the mycelium to l-cystine. The CDO protein, detected as two bands of different mobility, appeared earlier in comparison to mRNA (1 h) and culminated after 24 h. More mobile form prevailed after 4.5 h. The comparison of the dynamics in the Cdo mRNA and CDO protein levels indicates that T. mentagrophytes responds to l-cystine by increased transcription and apparently decreased degradation of the CDO and by changing towards higher mobility molecular form, similar to previous reports describing mammalian analogue.
- MeSH
- cysteindioxygenasa genetika metabolismus MeSH
- cystin metabolismus MeSH
- fungální proteiny genetika metabolismus MeSH
- lidé MeSH
- mycelium enzymologie genetika růst a vývoj metabolismus MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- regulace genové exprese enzymů * MeSH
- tinea mikrobiologie MeSH
- Trichophyton enzymologie genetika růst a vývoj fyziologie MeSH
- upregulace MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- chemický průmysl MeSH
- cystin analýza metabolismus MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- nehty chemie MeSH
- pracovní expozice MeSH
- rostliny chemie MeSH
- vanad moč MeSH
- vlasy, chlupy chemie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- srovnávací studie MeSH
