The objective of our in vitro study was to quantify the biochemical profile where the total polyphenol, flavonoid and phenolic acid content was determined. The antioxidant potential of microgreen extract from Trigonella foenum-graecum L., was measured molybdenum reducing power assay. Specifically, the study assessed parameters such as metabolic activity (AlamarBlueTM assay), membrane integrity (CFDA-AM assay), mitochondrial potential (JC-1 assay), as well as reactive oxygen species generation (NBT assay). In addition, the steroid hormone release in TM3 murine Leydig cells after 12 h and 24 h exposures were quantified by enzyme-linked immunosorbent assay. The gained results indicate the highest value in total flavonoid content (182.59+/-2.13 mg QE) determination, supported by a significant (108.25+/-1.27 mg TE) antioxidant activity. The effects on metabolic activity, cell membrane integrity, and mitochondrial membrane potential were found to be both time- and dose-dependent. Notably, a significant suppression in reactive oxygen species generation was confirmed at 150, 200 and 250 microg/ml after 24 h exposure. In addition, progesterone and testosterone release was stimulated up to 250 microg/ml dose of Trigonella, followed by a decline in both steroid production at 300 and 1000 microg/ml. Our results indicate, that Trigonella at lower experimental doses (up to 250 microg/ml) may positively affect majority of monitored cell parameters in TM3 Leydig cells. Overleaf, increasing experimental doses may negatively affect the intracellular parameters already after 12 h of in vitro exposure. Key words Microgreens, Trigonella foenum-graecum L., Fenugreek, Leydig cells, Male reproduction.

• MeSH
• antioxidancia farmakologie   MeSH
• buněčné linie MeSH
• fytonutrienty farmakologie   MeSH
• Leydigovy buňky * účinky léků   metabolismus   MeSH
• membránový potenciál mitochondrií účinky léků   MeSH
• myši MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• rostlinné extrakty * farmakologie   MeSH
• testosteron metabolismus   MeSH
• Trigonella * chemie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Schizophrenia is associated with numerous abnormalities, including imbalances in all hormonal axes, among which steroids play a major role. Steroidomic studies therefore represent a promising tool for early diagnosis and appropriate treatment of schizophrenia. A total of 51 adult male schizophrenics aged 27 (22, 34) years (shown as median with quartiles) and 16 healthy controls (HCs) aged 28 (25, 32) years were enrolled into this study. Our results showed the effective differentiation of men with schizophrenia from controls based on steroidomic profiles. We also found an altered metabolic pathway from pregnenolone and its sulfate (PREG/S) to cortisol in schizophrenics with several metabolic bottlenecks such as lower PREG levels due to increased PREG sulfation and/or suppressed PREGS desulfation and attenuated conversion of 17-hydroxy-PREG to 17-hydroxy-progesterone, as well as the results suggestive of suppressed CYP11B1 activity. In contrast, steroid molar ratios suggested two counterregulatory steps involving increased conversion of PREG/S to 17-hydroxy-PREG/S and decreased conversion of cortisol to cortisone, which may maintain unchanged basal cortisol levels but may not ensure a sufficient cortisol response to stress. Our data also indicated a trend to higher 7α-, 7β-, and 16α-hydroxylation that may counteract the autoimmune complications and proinflammatory processes accompanying schizophrenia. Finally, a possible suppression of HSD17B3 activity was suggested, resulting in decreased circulating testosterone levels with increased androstenedione levels.

• MeSH
• dospělí MeSH
• hydrokortison metabolismus   krev   MeSH
• lidé MeSH
• mladý dospělý MeSH
• pregnenolon metabolismus   krev   MeSH
• schizofrenie * metabolismus   MeSH
• steroidy metabolismus   MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Příručka se zaměřuje na metody různých laboratorních vyšetření a na porozumění jejich výsledkům. Určeno odborné i široké veřejnosti.; Přehledný, praktický a dobře srozumitelný průvodce po laboratorních vyšetřeních a hodnotách je určen široké čtenářské veřejnosti. Kniha je rozdělena do tří částí - v první části jsou stručně popsány běžné laboratorní metody a postupy při získávání a zpracování vzorků, je také ukázáno jak biochemická laboratoř funguje a jaké se při práci v ní mohou vyskytnout chyby a problémy. Hlavní část průvodce obsahuje abecedně řazené laboratorní hodnoty s různými odkazy a vysvětlivkami. Třetí část vysvětluje základní laboratorní a biochemické pojmy a běžně používané zkratky.

• MeSH
• klinické laboratorní techniky * MeSH
• referenční hodnoty MeSH
• zkreslení výsledků (epidemiologie) MeSH
• Publikační typ
• populární práce MeSH
• příručky MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• chemie, klinická chemie

BACKGROUND: Causative genetic variants cannot yet be found for many disorders with a clear heritable component, including chronic fatigue disorders like myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). These conditions may involve genes in difficult-to-align genomic regions that are refractory to short read approaches. Structural variants in these regions can be particularly hard to detect or define with short reads, yet may account for a significant number of cases. Long read sequencing can overcome these difficulties but so far little data is available regarding the specific analytical challenges inherent in such regions, which need to be taken into account to ensure that variants are correctly identified. Research into chronic fatigue disorders faces the additional challenge that the heterogeneous patient populations likely encompass multiple aetiologies with overlapping symptoms, rather than a single disease entity, such that each individual abnormality may lack statistical significance within a larger sample. Better delineation of patient subgroups is needed to target research and treatment. METHODS: We use nanopore sequencing in a case of unexplained severe fatigue to identify and fully characterise a large inversion in a highly homologous region spanning the AKR1C gene locus, which was indicated but could not be resolved by short-read sequencing. We then use GC-MS/MS serum steroid analysis to investigate the functional consequences. RESULTS: Several commonly used bioinformatics tools are confounded by the homology but a combined approach including visual inspection allows the variant to be accurately resolved. The DNA inversion appears to increase the expression of AKR1C2 while limiting AKR1C1 activity, resulting in a relative increase of inhibitory GABAergic neurosteroids and impaired progesterone metabolism which could suppress neuronal activity and interfere with cellular function in a wide range of tissues. CONCLUSIONS: This study provides an example of how long read sequencing can improve diagnostic yield in research and clinical care, and highlights some of the analytical challenges presented by regions containing tandem arrays of genes. It also proposes a novel gene associated with a novel disease aetiology that may be an underlying cause of complex chronic fatigue. It reveals biomarkers that could now be assessed in a larger cohort, potentially identifying a subset of patients who might respond to treatments suggested by the aetiology.

• MeSH
• biologické markery MeSH
• hydroxysteroiddehydrogenasy MeSH
• lidé MeSH
• syndrom chronické únavy * MeSH
• tandemová hmotnostní spektrometrie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Estrogen receptor alpha (ER) is a key biomarker for breast cancer, and the presence or absence of ER in breast and other hormone-dependent cancers decides treatment regimens and patient prognosis. ER is activated after ligand binding - typically by steroid. 2682 steroid compounds were used in a molecular docking study to identify novel ligands for ER and to predict compounds that may show anticancer activity. The effect of the most promising compounds was determined by a novel luciferase reporter assay. Two compounds, 7 and 12, showing ER inhibitory activity comparable to clinical inhibitors such as tamoxifen or fulvestrant were selected. We propose that the inhibitory effect of compounds 7 and 12 on ER is related to the presence of a double bond in their D-ring, which may protect against ER activation by reducing the electron density of the keto group, or may undergo metabolism leading to an active compound. Western blotting revealed that compound 12 decreased the level of ER in the breast cancer cell line MCF7, which was associated with reduced expression of both isoforms of the progesterone receptor, a well-known downstream target of ER. However, compound 12 has a different mechanism of action from fulvestrant. Furthermore, we found that compound 12 interferes with mitochondrial functions, probably by disrupting the electron transport chain, leading to induction of the intrinsic apoptotic pathway even in ER-negative breast cancer cells. In conclusion, the combination of computational and experimental methods shown here represents a rapid approach to determine the activity of compounds towards ER. Our data will not only contribute to research focused on the regulation of ER activity but may also be useful for the further development of novel steroid receptor-targeted drugs applicable in clinical practice.

• MeSH
• alfa receptor estrogenů genetika   metabolismus   MeSH
• estradiol farmakologie   terapeutické užití   MeSH
• estron * farmakologie   MeSH
• fulvestrant farmakologie   terapeutické užití   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádory prsu * farmakoterapie   metabolismus   MeSH
• receptory pro estrogeny metabolismus   MeSH
• simulace molekulového dockingu MeSH
• tamoxifen farmakologie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Epidemiological studies suggest an association between Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM). This study aimed to investigate the pathophysiological markers of AD vs. T2DM for each sex separately and propose models that would distinguish control, AD, T2DM, and AD-T2DM comorbidity groups. AD and T2DM differed in levels of some circulating steroids (measured mostly by GC-MS) and in other observed characteristics, such as markers of obesity, glucose metabolism, and liver function tests. Regarding steroid metabolism, AD patients (both sexes) had significantly higher sex hormone binding globulin (SHBG), cortisol, and 17-hydroxy progesterone, and lower estradiol and 5α-androstane-3α,17β-diol, compared to T2DM patients. However, compared to healthy controls, changes in the steroid spectrum (especially increases in levels of steroids from the C21 group, including their 5α/β-reduced forms, androstenedione, etc.) were similar in patients with AD and patients with T2DM, though more expressed in diabetics. It can be assumed that many of these steroids are involved in counter-regulatory protective mechanisms that mitigate the development and progression of AD and T2DM. In conclusion, our results demonstrated the ability to effectively differentiate AD, T2DM, and controls in both men and women, distinguish the two pathologies from each other, and differentiate patients with AD and T2DM comorbidities.

• MeSH
• Alzheimerova nemoc * metabolismus   MeSH
• androstendion MeSH
• diabetes mellitus 2. typu * diagnóza   epidemiologie   MeSH
• komorbidita MeSH
• lidé MeSH
• steroidy metabolismus   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Kromě rizika selhání antikoncepce, které hrozí u eslikarbazepinu, felbamátu, fenobarbitalu, fenytoinu, karbamazepinu, oxcarbazepinu, perampanelu, primidonu, rufinamidu a vyšších hladin topiramátu, má klinický význam rovněž vliv antikoncepce na hladinu lamotriginu a případně topiramátu. Estrogenní komponenta výrazně snižuje hladinu lamotriginu s nutností navýšit dávky. V týdnu bez antikoncepce pak stoupá riziko nežádoucích účinků spojených s vysokou hladinou lamotriginu. Podání čistě progestinové antikoncepce při léčbě lamotriginem může způsobit selhání antikoncepce z důvodu mírného zvýšení clearance progestinu. Vliv na hormonální antikoncepci nemají klonazepam, etosuximid, gabapentin, kys. valproová, lacosamid, levetiracetam, pregabalin, retigabin, tiagabin, vigabatrin, zonisamid. Nebylo hodnoceno a nepředpokládá se u klobazamu. U stiripentolu a sulthiamu je předpokládán vzestup hladiny kontraceptiva a možná potřeba redukce dávky.

The metabolism of contraceptives is enhanced and thereby contraceptive failure might occur in combination with carbamazepine, eslicarbazepine, felbamate, phenobarbital, phenytoin, oxcarbazepine, perampanel, primidone, rufinamide or higher levels of topiramate. Estrogen component considerably declines lamotrigine level with the necessity to increase the dose. Lamotrigine concentrations consequently significantly increase during the hormonal contraceptive washout week and may be associated with intermittent lamotrigine-related toxicity. Lamotrigine produces a modest reduction in the progesterone level which might result in contraceptive failure in patients using the progesterone-only pill. The metabolism of hormonal contraceptives is no affected with: clonazepam, ethosuximide, gabapentin, lacosamide, levetiracetam, pregabalin, retigabine, tiagabine, vigabatrin, valproic acid, zonisamid. The effect has not been evaluated in clobazam. A pharmacokinetic interaction would not be anticipated. It is not known whether stiripentol or sulthiame affect hormonal contraception, but they can increase plasma level of hormonal contraceptives and thus necessitate lower doses to be prescribed.

• MeSH
• antikonvulziva * farmakologie   MeSH
• hormonální antikoncepce MeSH
• kontraceptiva hormonální farmakologie   MeSH
• lamotrigin farmakologie   MeSH
• léková kontraindikace MeSH
• lékové interakce * MeSH
• lidé MeSH
• topiramat farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

The aim of this in vitro study was to examine the dose-dependent effects of iron as a potential endocrine disruptor in relation to the release of sexual steroid hormones by a human adrenocortical carcinoma (NCI-H295R) cell line. The cells were exposed to different concentrations (3.90, 62.50, 250, 500, 1000 μM) of FeSO4.7H2O and compared with the control group (culture medium without FeSO4.7H2O). Cell viability was measured by the metabolic activity assay. Quantification of sexual steroid production was performed by enzyme-linked immunosorbent assay. Following 48 h culture of the cells in the presence of FeSO4.7H2O, significantly (P < 0.001) increased production of progesterone was observed at the lowest concentration (3.90 μM) of FeSO4.7H2O, whereas the lowest release of progesterone by NCIH295R cells was noted after addition of 1000 μM of FeSO4.7H2O, which did not elicit cytotoxic action (P > 0.05). Testosterone production was substantially increased at the concentrations ≤ 62.50 μM of FeSO4.7H2O. Lower levels of testosterone were recorded in the groups with higher concentrations (≥ 250 μM) of FeSO4.7H2O (P > 0.05). The presented data suggest that iron has no endocrine disruptive effect on the release of sexual steroid hormones, but its toxicity may be reflected at other points of the steroidogenesis pathway.

• MeSH
• adrenokortikální karcinom * MeSH
• adrenokortikální nádory * MeSH
• buněčné kultury MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• železo MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Vysokoškolská učebnice, která se zaměřuje na lékařskou biochemii.; Dvoudílný učební text je určen pro studující biochemie na lékařských fakultách, kde tento předmět navazuje na kurz chemie. Obsahuje celkový přehled metabolismu, kapitoly o dýchacím řetězci a aerobní fosforylaci následované výkladem o citrátovém cyklu, dále pak popis katabolických a anabolických přeměn jednotlivých živin a stavebních látek v organismu. Znalosti základních přeměn jsou poté aplikovány na jednotlivé tkáně v organismu. Učebnice lékařské biochemie přináší také detailní informace o hormonech. Při přípravě druhého vydání byl text revidován a doplněn. Některé části byly upraveny tak, aby více akcentovaly vztahy mezi jednotlivými metabolickými přeměnami. Zvláštní pozornost byla věnována regulaci fyziologických dějů, nově je zařazena kapitola o tukové tkáni a jejím metabolismu.

• MeSH
• biochemie MeSH
• klinická chemie MeSH

• Konspekt
• Biochemie. Molekulární biologie. Biofyzika
• Učební osnovy. Vyučovací předměty. Učebnice
• NLK Obory
• biochemie
• chemie, klinická chemie
• NLK Publikační typ
• učebnice vysokých škol

Publikace se zaměřuje na diagnostiku a léčbu nemocí endokrinního systému. Určeno odborné veřejnosti.; Přehled pro lékaře, kteří nejsou endokrinology či diabetology, o možných endokrinologických onemocněních.

• MeSH
• diagnostické techniky endokrinologické MeSH
• nemoci endokrinního systému diagnóza   terapie   MeSH
• Publikační typ
• monografie MeSH

• Konspekt
• Fyziologie člověka a srovnávací fyziologie
• NLK Obory
• endokrinologie