Dokument, který se zaměřuje na plánování lepšího systému vzdělávání v Česku pomocí různých strategií. Určeno odborné veřejnosti.

• MeSH
• dějiny 21. století MeSH
• odborná způsobilost MeSH
• řízení kvality MeSH
• sociologické faktory MeSH
• strategické plánování MeSH
• veřejná politika MeSH
• výchova a vzdělávání MeSH
• Check Tag
• dějiny 21. století MeSH
• Geografické názvy
• Česká republika MeSH

• Konspekt
• Vzdělávací a výchovná politika
• NLK Obory
• pedagogika
• politologie, politika, zdravotní politika
• sociologie
• NLK Publikační typ
• dokumenty
• brožury

1. The underlying microbial metabolic activity toward xenobiotics is among the least explored factors contributing to the inter-individual variability in drug response. 2. Here, we analyzed the effect of microbiota on a non-steroidal anti-inflammatory drug nabumetone. 3. First, we cultivated the drug with the selected gut commensal and probiotic bacteria under both aerobic and anaerobic conditions and analyzed its metabolites by high-performance liquid chromatography (HPLC) with UV detection. To analyze the effect of microbiota on nabumetone pharmacokinetics in vivo, we administered a single oral dose of nabumetone to rodents with intentionally altered gut microbiome - either rats treated for three days with the antibiotic imipenem or to germ-free mice. Plasma levels of its main active metabolite 6 methoxy-2-naphthylacetic acid (6-MNA) were analyzed at pre-specified time intervals using HPLC with UV/fluorescence detection. 4. We found that nabumetone is metabolized by bacteria to its non-active metabolites and that this effect is stronger under anaerobic conditions. Although in vivo, none of the pharmacokinetic parameters of 6-MNA was significantly altered, there was a clear trend towards an increase of the AUC, Cmax and t1/2 in rats with reduced microbiota and germ-free mice.

• MeSH
• anaerobióza MeSH
• antibakteriální látky farmakologie   MeSH
• antiflogistika nesteroidní metabolismus   farmakokinetika   MeSH
• biologická dostupnost MeSH
• imipenem farmakologie   MeSH
• kyseliny naftalenoctové metabolismus   farmakokinetika   MeSH
• myši inbrední BALB C MeSH
• nabumeton metabolismus   farmakokinetika   MeSH
• organismy bez specifických patogenů MeSH
• potkani Wistar MeSH
• střevní mikroflóra účinky léků   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• audiovizuální média MeSH
• časopisecké články MeSH

P-glycoprotein (P-gp) is a membrane-bound transporter encoded by Mdr1a/Abcb1a and Mdr1b/Abcb1b genes in rodents involved in the efflux of cytotoxic chemicals and metabolites from cells. Modulation of its activity influences P-gp-mediated drug delivery and drug-drug interaction (DDI). In the current study, we tested the effects of fenofibrate on P-gp mRNA and protein content in non-obese model of metabolic syndrome. Males hereditary hypertriglyceridemic rats (HHTg) were fed standard laboratory diet (STD) (Controls) supplemented with micronized fenofibrate in lower (25 mg/kg b. wt./day) or in higher (100 mg/kg b. wt./day) dose for 4 weeks. Liver was used for the subsequent mRNA and protein content analysis. Fenofibrate in lower dose decreased hepatic Mdr1a by 75% and Mdr1b by 85%, while fenofibrate in higher dose decreased Mdr1a by 90% and Mdr1b by 92%. P-gp protein content in the liver was decreased by 74% in rat treated with fenofibrate at lower dose and by 88% in rats using fenofibrate at higher dose. These findings demonstrate for the first time that fenofibrate decreases both mRNA and protein amount of P-gp and suggest that fenofibrate could affect bioavailability and interaction of drugs used to treat dyslipidemia-induced metabolic disorders.

• Publikační typ
• časopisecké články MeSH

BACKGROUND AND OBJECTIVES: The probiotic bacterium Escherichia coli strain Nissle 1917 has previously been shown to alter the pharmacokinetics of amiodarone. The aim of this study was to determine whether the probiotic bacterium Lactobacillus casei produces similar alterations in amiodarone disposition. METHODS: A suspension of live probiotic bacteria L. casei strain DN-114 001 (1.5 × 10(9) CFU/dose; probiotic pre-treated group) or a saline solution (control group) was administered directly into the stomach of male Wistar rats (N = 30 in each group) by oral gavage daily for 7 consecutive days. On the eighth day, all rats (N = 60) were given a single oral dose of an amiodarone hydrochloride suspension (model drug; 50 mg/kg). The concentrations of amiodarone and of its main metabolite N-desethylamiodarone were determined in rat plasma by high-performance liquid chromatography. RESULTS: Comparison of the pharmacokinetics of amiodarone in the control group and probiotic pre-treated group revealed that the peak plasma concentration of amiodarone was delayed by >2 h in the probiotic pre-treated group. The plasma level of N-desethylamiodarone was unchanged in the probiotic pre-medicated group and its pharmacokinetic parameters were not altered. CONCLUSIONS: The slower absorption of amiodarone in the probiotic pre-treated rats compared to the control ones and the unchanged pharmacokinetics of its main metabolite suggest that the probiotic strain of L. casei DN-114 001 has probably no clinical consequences as the difference was not statistically significant.

• MeSH
• amiodaron aplikace a dávkování   krev   farmakokinetika   MeSH
• aplikace orální MeSH
• krysa rodu rattus MeSH
• Lactobacillus casei * MeSH
• probiotika aplikace a dávkování   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

1. To compare the effectiveness of different drug forms of silymarin: standardized extract of silymarin (SS), micronized silymarin (MS) and silymarin in the form of phytosome (PS) on dyslipidemia and liver fat accumulation in a model of metabolic syndrome, in non-obese hereditary hypertriglyceridemic rats. The second aim of this study was to slightly uncover the silymarin action on enzymes and proteins involved in cholesterol metabolism and excretion. 2. Silymarin administered to hereditary hypertriglyceridemic rats as dietary supplements (1%) for 4 weeks significantly lowered the plasma levels of triglycerides, total cholesterol and markedly increased HDL cholesterol level. Western blot analyses showed significant increase in the protein expression of CYP7A1 and CYP4A and increase in protein expression of selected ABC transporters. Silymarin in the form of phytosome and micronized silymarin were more effective forms of silymarin. 3. These findings suggest that silymarin may favorably affect the metabolism of cholesterol and triglycerides in rats with metabolic syndrome. Raising HDL levels suggests potentially important anti-atherogenic effect of silymarin. The changes in expression of cytochromes P450 and ABC transporters involved in cholesterol metabolism and excretion could be partially responsible for the hypolipidemic effect of silymarin.

• MeSH
• ABC transportéry metabolismus   MeSH
• biologická dostupnost MeSH
• cholesterol-7-alfa-hydroxylasa metabolismus   MeSH
• cytochrom P450 CYP4A metabolismus   MeSH
• dyslipidemie krev   komplikace   farmakoterapie   MeSH
• játra účinky léků   enzymologie   MeSH
• lipidy krev   MeSH
• metabolický syndrom krev   komplikace   farmakoterapie   MeSH
• potkani Wistar MeSH
• silymarin farmakologie   terapeutické užití   MeSH
• western blotting MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The exposure of human cells to oxidative stress leads to the oxidation of biomolecules such as lipids, proteins and nuclei acids. In this study, the oxidation of lipids, proteins and DNA was studied after the addition of hydrogen peroxide and Fenton reagent to cell suspension containing human leukemic monocyte lymphoma cell line U937. EPR spin-trapping data showed that the addition of hydrogen peroxide to the cell suspension formed hydroxyl radical via Fenton reaction mediated by endogenous metals. The malondialdehyde HPLC analysis showed no lipid peroxidation after the addition of hydrogen peroxide, whereas the Fenton reagent caused significant lipid peroxidation. The formation of protein carbonyls monitored by dot blot immunoassay and the DNA fragmentation measured by comet assay occurred after the addition of both hydrogen peroxide and Fenton reagent. Oxidative damage of biomolecules leads to the formation of singlet oxygen as conformed by EPR spin-trapping spectroscopy and the green fluorescence of singlet oxygen sensor green detected by confocal laser scanning microscopy. It is proposed here that singlet oxygen is formed by the decomposition of high-energy intermediates such as dioxetane or tetroxide formed by oxidative damage of biomolecules.

• MeSH
• elektronová paramagnetická rezonance MeSH
• hydroxylový radikál toxicita   MeSH
• karbonylace proteinů účinky léků   MeSH
• kometový test MeSH
• konfokální mikroskopie MeSH
• leukemie metabolismus   patologie   MeSH
• lidé MeSH
• malondialdehyd analýza   MeSH
• nádorové buněčné linie MeSH
• oxidační stres účinky léků   MeSH
• peroxid vodíku toxicita   MeSH
• peroxidace lipidů účinky léků   MeSH
• singletový kyslík metabolismus   MeSH
• viabilita buněk účinky léků   MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• železo toxicita   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVES: The aim of this study was to investigate whether rosuvastatin affects expression and activity of rat CYP2C6. This cytochrome P450 is considered to be a counterpart of human CYP2C9, which metabolizes many drugs, including diclofenac, ibuprofen or warfarin. DESIGN: Male hereditary hypertriglyceridemic (HHTg) rats were fed standard laboratory diet (STD) or high cholesterol diet (HCD: STD + 1% of cholesterol w/w + 10% of lard fat w/w) for 21 days. A third group of rats were fed high a cholesterol diet with rosuvastatin added (0.03% w/w). Expression of CYP2C6 was measured in liver samples using real-time PCR (mRNA level) and Western blotting (protein level). Formation of diclofenac metabolites (typical enzyme activity of CYP2C6) was analyzed using HPLC with UV detection. RESULTS: Administration of rosuvastatin to HHTg rats resulted in significantly increased mRNA expression and enzyme activity in HCD-fed animals; changes of CYP2C6 protein were non-significant. These results suggest that CYP2C6 expression and activity are positively affected by rosuvastatin in hereditary hypertriglyceridemic rats after intake of HCD. CONCLUSION: The results presented open the possibility that in humans, rosuvastatin may affect the metabolism of many drugs by influencing expression and activity of CYP2C6 (counterpart of human CYP2C9). Further studies are needed to elucidate the effects of this statin on CYP2C9 in humans.

• MeSH
• aromatické hydroxylasy antagonisté a inhibitory   metabolismus   MeSH
• cholesterol dietní farmakologie   MeSH
• fluorbenzeny farmakologie   MeSH
• genetická transkripce účinky léků   MeSH
• hyperlipoproteinemie typ IV farmakoterapie   genetika   metabolismus   MeSH
• jaterní mikrozomy účinky léků   enzymologie   MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• messenger RNA metabolismus   MeSH
• mutantní kmeny potkanů MeSH
• potkani Wistar MeSH
• pyrimidiny farmakologie   MeSH
• regulace genové exprese enzymů účinky léků   MeSH
• statiny farmakologie   MeSH
• steroid-21-hydroxylasa antagonisté a inhibitory   genetika   metabolismus   MeSH
• sulfonamidy farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: The aim of the study was to find whether probiotic Lactobacillus casei influences the expression or the activity of cytochromes P450 (CYP) and whether it has an influence on the level of CYP mRNA in male rats. DESIGN: Live bacterial suspension of L. casei was administered orally (gavage) to healthy male Wistar rats daily for 7 days. Control group of rats was treated with the saline solution. Sections of the duodenum, jejunum, ileum, caecum and colon were dissected from each experimental animal. In all individual samples, the expression of selected CYPs was determined by Western blotting. The levels of expression of CYPs were also evaluated by mRNA using the real-time PCR method. RESULTS: There were changes observed in the expression of CYP enzymes and in the CYP mRNA levels along the intestine after application of L. casei. The expression of CYP1A1 enzyme was found to be decreased in the proximal part of the jejunum and colon, CYP1A1 mRNA level was decreased in the distal part of the jejunum, ileum and caecum. Thus, the changes in CYP1A1 protein or mRNA were observed along the intestine of male rats. Similarly, a decreased expression of the caecal CYP2E1 mRNA and of the duodenal CYP3A9 mRNA after treatment of rats with L. casei was found. CONCLUSION: Probiotic L. casei might be able to contribute to prevention against colorectal cancer by decreasing levels of certain forms of xenobiotic-metabolizing enzymes; moreover, in general, there is a possibility of interactions with concomitantly taken pharmacotherapeutic agents.

• MeSH
• aktivace enzymů účinky léků   MeSH
• aromatické hydroxylasy genetika   metabolismus   MeSH
• cytochrom P-450 CYP2E1 genetika   metabolismus   MeSH
• cytochrom P-450 CYP3A genetika   metabolismus   MeSH
• cytochromy genetika   metabolismus   MeSH
• játra účinky léků   metabolismus   mikrobiologie   MeSH
• krysa rodu rattus MeSH
• Lactobacillus casei fyziologie   MeSH
• messenger RNA metabolismus   MeSH
• potkani Wistar MeSH
• probiotika farmakologie   MeSH
• regulace genové exprese enzymů účinky léků   MeSH
• steroid-16-alfa-hydroxylasa genetika   metabolismus   MeSH
• steroid-21-hydroxylasa genetika   metabolismus   MeSH
• střeva účinky léků   metabolismus   mikrobiologie   MeSH
• systém (enzymů) cytochromů P-450 genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH

• Publikační typ
• abstrakty MeSH