SulT
Dotaz
Zobrazit nápovědu
1 CD-ROM
Neuroactive steroids (dehydroepiandrosterone, pregnenolone) and their sulfates act as modulators of glutamate and gamma-aminobutyrate type A receptors in the brain The physiological ratio of these neuromodulators is maintained by two enzymes present in the brain, namely, steroid sulfatase (STS) and steroid sulfuryl transferase (SULT). Following previous determination of their activities in monkey brains, their activities were evaluated in human brain tumors. Radioimmunoassay and GC-MS were used for determination of products. Both enzyme activities were measured in the 55 most frequent human brain tumors (glioblastomas, pituitary adenomas, meningiomas, astrocytomas). Significant differences were found in STS activity among investigated types of tumors except the pair of pituitary adenomas-glioblastomas, while significant differences were found in SULT activity among investigated types of tumors. Spontaneous tendency to form clusters was revealed when both enzyme activities were taken as coordinates. Clustering indicated an individual metabolic behavior of glioblastomas and 72.7% of pituitary adenomas. Astrocytomas, meningiomas and remaining 27.3% pituitary adenomas showed similarities in both enzymes' activities. Differences in STS and SULT activity did not depend on the sex or age of subjects.
- MeSH
- adenom enzymologie MeSH
- astrocytom enzymologie MeSH
- dospělí MeSH
- financování organizované MeSH
- gliosarkom enzymologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- meningeální nádory enzymologie MeSH
- meningeom enzymologie MeSH
- nádory hypofýzy enzymologie MeSH
- nádory mozku enzymologie MeSH
- plynová chromatografie s hmotnostně spektrometrickou detekcí MeSH
- radioimunoanalýza MeSH
- steryl-sulfatasa analýza metabolismus MeSH
- sulfotransferasy analýza metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
2,3-Dehydrosilybin A and 2,3-dehydrosilybin B are a pair of enantiomers formed by the oxidation of the natural flavonolignans silybin A and silybin B, respectively. However, the antioxidant activity of 2,3-dehydrosilybin molecules is much stronger than that of their precursors. Here, we investigated the biotransformation of pure 2,3-dehydrosilybin A and 2,3-dehydrosilybin B in isolated human hepatocytes, and we also aimed to identify human UDP-glucuronosyltransferases (UGTs) and sulfotransferases (SULTs) with activity toward their respective enantiomers. After incubation with hepatocytes, both 2,3-dehydrosilybin A and 2,3-dehydrosilybin B were converted to hydroxyl derivatives, methylated hydroxyl derivatives, methyl derivatives, sulfates, and glucuronides. The products of direct conjugations predominated over those of oxidative metabolism, and glucuronides were the most abundant metabolites. Furthermore, we found that recombinant human UGTs 1A1, 1A3, 1A7, 1A8, 1A9, and 1A10 were capable of catalyzing the glucuronidation of both 2,3-dehydrosilybin A and 2,3-dehydrosilybin B. UGTs 1A1 and 1A7 showed the highest activity toward 2,3-dehydrosilybin A, and UGT1A9 showed the highest activity toward 2,3-dehydrosilybin B. The sulfation of 2,3-dehydrosilybin A and B was catalyzed by SULTs 1A1*1, 1A1*2, 1A2, 1A3, 1B1, 1C2, 1C4, and 1E1, of which SULT1A3 exhibited the highest activity toward both enantiomers. We conclude that 2,3-dehydrosilybin A and B are preferentially metabolized by conjugation reactions, and that several human UGT and SULT enzymes may play a role in these conjugations.
- Publikační typ
- časopisecké články MeSH
Natural phenolic compounds are known to be metabolized by phase II metabolic reactions. In this study, we examined the in vitro sulfation of the main constituents of silymarin, an herbal remedy produced from the fruits of the milk thistle. The study focused on major flavonolignan constituents, including silybin A, silybin B, isosilybin A, isosilybin B, silychristin, and silydianin, as well as the flavonoid taxifolin. Using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS), individual flavonolignans and taxifolin were found to be sulfated by human liver and human intestinal cytosols. Moreover, experiments with recombinant enzymes revealed that human sulfotransferases (SULTs) 1A1*1, 1A1*2, 1A2, 1A3, 1B1, 1C4, and 1E1 catalyzed the sulfation of all of the tested compounds, with the exception of silydianin, which was not sulfated by SULT1B1 and SULT1C4. The sulfation products detected were monosulfates, of which some of the major ones were identified as silybin A 20-O-sulfate, silybin B 20-O-sulfate, and isosilybin A 20-O-sulfate. Further, we also observed the sulfation of the tested compounds when they were tested in the silymarin mixture. Sulfates of flavonolignans and of taxifolin were produced by incubating silymarin with all of the above SULT enzymes, with human liver and intestinal cytosols, and also with human hepatocytes, even though the spectrum and amount of the sulfates varied among the metabolic models. Considering our results and the expression patterns of human sulfotransferases in metabolic tissues, we conclude that flavonolignans and taxifolin can potentially undergo both intestinal and hepatic sulfation, and that SULTs 1A1, 1A3, 1B1, and 1E1 could be involved in the biotransformation of the constituents of silymarin.
- Publikační typ
- časopisecké články MeSH
3-Nitrobenzanthrone (3-NBA) is a suspected human carcinogen identified in diesel exhaust and air pollution. This article reviews the results of our laboratories showing which of the phase I and II enzymes are responsible for 3-NBA genotoxicity, participating in activation of 3-NBA and its human metabolite, 3-aminobenzanthrone (3-ABA), to species generating DNA adducts. Among the phase I enzymes, the most of the activation of 3-NBA in vitro is attributable to cytosolic NAD(P)H:quinone oxidoreductase (NQO1), while N,O-acetyltransferase (NAT), NAT2, followed by NAT1, sulfotransferase (SULT), SULT1A1 and, to a lesser extent, SULT1A2 are the major phase II enzymes activating 3- NBA. To evaluate the importance of hepatic cytosolic enzymes in relation to microsomal NADPH:cytochrome P450 (CYP) oxidoreductase (POR) in the activation of 3-NBA in vivo, we treated hepatic POR-null and wild-type C57BL/6 mice with 3-NBA or 3-ABA. The results indicate that 3-NBA is predominantly activated by cytosolic nitroreductases such as NQO1 rather than microsomal POR. In the case of 3-ABA, CYP1A1/2 enzymes are essential for the oxidative activation of 3-ABA in liver. However, cells in the extrahepatic organs have the metabolic capacity to activate 3-ABA to form DNA adducts, independently from CYP-mediated oxidation in the liver. Peroxidases such as prostaglandin H synthase, lactoperoxidase, myeloperoxidase, abundant in several extrahepatic tissues, generate DNA adducts, which are formed in vivo by 3-ABA or 3-NBA. The results suggest that both CYPs and peroxidases may play an important role in metabolism of 3-ABA to reactive species forming DNA adducts, participating in genotoxicity of this compound and its parental counterpart, 3-NBA.
- MeSH
- adukty DNA MeSH
- aktivace enzymů MeSH
- benz(a)anthraceny toxicita MeSH
- jaterní mikrozomy metabolismus MeSH
- karcinogeny životního prostředí toxicita MeSH
- látky znečišťující životní prostředí toxicita MeSH
- lidé MeSH
- peroxidasy metabolismus MeSH
- systém (enzymů) cytochromů P-450 metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
... Steiner unb bie tritií 13 -- ^runbíagen ber Steinernen Se^re 15 ber $efcí)id)te ber miffenícřjaftinen SUlet ...
64 stran ; 21 cm
- MeSH
- duševní procesy MeSH
- filozofie MeSH
- náboženství MeSH
- okultismus MeSH
- spiritualita MeSH
- Publikační typ
- monografie MeSH
- Konspekt
- Psychologie
- NLK Obory
- psychologie, klinická psychologie
Častí uživatelé (návštěvníci) zdravotnické péče jsou malá část pacientské populace, jejichž frekvence a způ¬sob konzultací se jeví jako nepřiměřené a obtížné. Podstata jejich zvláštního zdravotního chování vyplývá z koexistence tělesných a psychosociálních problémů z nedávné nebo vzdálené minulosti. Často je u nich přítomna některá úzkostná nebo depresivní porucha, jejíž odléčení způsob konzultací upravuje. Časté uží¬vání se zpravidla týká více míst ve zdravotnickém i sociálním systému. Znalost problému může snížit nega¬tivní emoce, které tito pacienti ve zdravotnických zařízeních vyvolávají.
Frequent users of health care are only a fraction of the patient population, the frequency and mode of con-sulting prove to be out of proportion and annoying. The nature of their healthwise behavior follows from the coexistence of body and psycho-social problems in their recent or more remote past. Often, there is pre-sent some anxious or depressive disturbance, the curing of which is effected by consultations. There are fre¬quent visits to a number of healthcare as well as sociál care systems. Knowledge of the problém can dimi-nish negative reactions that such patients evoke in healthcare facilities.
Ankylozující spondylitida (AS) představuje zánětlivé revmatické onemocnění postihující axiální skelet, které je charakterizováno zánětli-vou bolestí zad a strukturálními změnami axiálního skeletu zachycenými zobrazovacími metodami. Tyto změny mohou vést ve svém dů-sledku k poškození páteře s následnými funkčními změnami. Včasná diagnóza spojená s adekvátní léčbou a režimovými opatřeními vede k dosažení remise, či alespoň nízké aktivity onemocnění. Sekukinumab je plně humánní monoklonální protilátka inhibující interleukin 17, která prokázala dobrou klinickou účinnost v programu klinických studií MEASURE a je nyní využívána nejen v terapii ankylozující spondylitidy a psoriatické artritidy.
Ankylosing spondylitis (AS) is an inflammatory rheumatic disease that affects axial skeleton characterized by inflammatory back pain and structural changes of the axial skeleton that can be seen using imagining techniques. These changes may lead to spine damage with re-sulting functional changes. Timely diagnosis together with adequate treatment and regime adjustments leads to remission, or at least to low disease activity. Secukinumab is fully human monoclonal antibody inhibiting interleukine 17 that exhibited good clinical efficacy in the program of MEASURE clinical studies and is currently used not only in the therapy of ankylosing spondylitis and psoriatic arthritis.
- Klíčová slova
- Sekukinumab,
- MeSH
- ankylózující spondylitida * diagnóza farmakoterapie terapie MeSH
- biologická terapie MeSH
- humanizované monoklonální protilátky terapeutické užití MeSH
- lidé MeSH
- mladý dospělý MeSH
- receptory interleukinu-17 antagonisté a inhibitory terapeutické užití MeSH
- Check Tag
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
We studied the surface properties and cytocompatibil-ity of a grafted biopolymer, poly(3-hydroxybutyrate) (P3HB). P3HB was exposed to an inert argon plasma dis-charge, then grafted by 1,1 '-biphenyl-4,4 '-dithiol (BFD) and finally grafted by golden nanoparticles (nanospheres and nanorods). The surface properties were studied using multiple methods – goniometry, atomic force microscopy and X-ray photoelectron spectroscopy. Cytocompatibility was determined in vitro by studying adhesion, prolifera-tion and viability of vascular smooth muscle cells (VSMCs) from the aorta of Rattus norvegicus. The cyto-compatibility was compared for pristine, modified P3HB and standard tissue culture polystyrene (TCPS). Our re-sults show that surface morphology and wettability are affected by both plasma discharge and nanoparticles graft-ing. These changes suggest that the adhesion and prolifera-tion of VSMCs is enhanced more on the plasma modified and grafted substrate.
Efekt profylaktické opakované lokální aplikace chlorhexidinového laku byl prověřován v longitudinální studii trvající v průměru 20 měsíců. Studie byla provedena na souboru dětí ve věku 14–17 let s vysokou kazivostí (KPE zubů §§§ 5). V půlročních intervalech byl lokálně aplikován chlorhexidinový lak CERVITEC (Vivadent) a pacienti vyšetřovaní klinicky a mikro- biologicky (slinné hladiny S. mutans a laktobacilů). Výsledky ukázaly, že opakovaná aplikace chlorhexidinového laku signifikantně snižuje přírůstek zubního kazu a pozitivně ovlivňuje stav gingivy a množství povlaku ve srovnání s nálezy u kontrolní skupiny dětí bez aplikace chlor- hexidinu. Screeningové testy pro mikrobiologické vyšetřování kariogenních mikroorganismů ve slinách nemají reprodukovatelnou a dostatečnou prediktivní vypovídací schopnost. Lokální antibakteriální profylaxe kazu pomocí laku obsahujících chlorhexidin se jeví jako účinná a bezpečná metoda vhodná jako doplněk ústní hygieny a fluoridové prevence u jedinců se zvýšeným rizikem kazu.
The effect of repeated topical application of chlorhexidine (CLX)-containing varnish was evaluated in a three-year-clinical trial. The study was conducted on a group of children (aged 14–17) with high caries experience (DMFT §§§ 5). The CLX containing varnish CERVITEC (Vivadent) was applied in six-month-time intervals and patients were repeatedly examined clinically and bacteriologically (salivary mutans streptococci and lactobacilli). Re- sults showed that repeated application of CERVITEC varnish significantly decreased caries increment and improved gingival status and oral hygiene when compared with findings in the control group without CLX application. Screening evaluation of salivary levels of cariogennic bacteria did not reveal reproducible and sufficient predictive value. The topical antibacterial prophylaxis of caries by the CLX containing varnish is an effective and safe method suitable as an adjunct means to oral hygiene and fluoride prevention in individuals at higher risk of dental caries.
- MeSH
- chlorhexidin aplikace a dávkování terapeutické užití MeSH
- dítě MeSH
- finanční podpora výzkumu jako téma MeSH
- lidé MeSH
- longitudinální studie MeSH
- náchylnost k zubnímu kazu MeSH
- orální zdraví MeSH
- Streptococcus mutans MeSH
- zubní kaz diagnóza farmakoterapie prevence a kontrola MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- přehledy MeSH
- srovnávací studie MeSH
