Toxicity of dioxin-like compounds (DLCs), such as polychlorinated dibenzo-p-dioxins, dibenzofurans and biphenyls, is largely mediated via aryl hydrocarbon receptor (AhR) activation. AhR-mediated gene expression can be tissue-specific; however, the inducibility of AhR in the lungs, a major target of DLCs, remains poorly characterized. In this study, we developed relative effective potencies (REPs) for a series of DLCs in both rodent (MLE-12, RLE-6TN) and human (A549, BEAS-2B) lung and bronchial epithelial cell models, using expression of both canonical (CYP1A1, CYP1B1) and less well characterized (TIPARP, AHRR, ALDH3A1) AhR target genes. The use of rat, murine and human cell lines allowed us to determine both species-specific differences in sensitivity of responses to DLCs in lung cellular models and deviations from established WHO toxic equivalency factor values (TEF) values. Finally, expression of selected AhR target genes was determined in vivo, using lung tissues of female rats exposed to a single oral dose of DLCs and compared with the obtained in vitro data. All cell models were highly sensitive to DLCs, with murine MLE-12 cells being the most sensitive and human A549 cells being the least sensitive. Interestingly, we observed that four AhR target genes were more sensitive than CYP1A1 in lung cell models (CYP1B1, AHRR, TIPARP and/or ALDH3A1). We found some deviations, with strikingly low REPs for polychlorinated biphenyls PCBs 105, 167, 169 and 189 in rat RLE-6TN cells-derived REPs for a series of 20 DLCs evaluated in this study, as compared with WHO TEF values. For other DLCs, including PCBs 126, 118 and 156, REPs were generally in good accordance with WHO TEF values. This conclusion was supported by in vivo data obtained in rat lung tissue. However, we found that human lung REPs for 2,3,4,7,8-pentachlorodibenzofuran and PCB 126 were much lower than the respective rat lung REPs. Furthermore, PCBs 118 and 156 were almost inactive in these human cells. Our observations may have consequences for risk assessment. Given the differences observed between rat and human data sets, development of human-specific REP/TEFs, and the use of CYP1B1, AHRR, TIPARP and/or ALDH3A1 mRNA inducibility as sensitive endpoints, are recommended for assessment of relative effective potencies of DLCs.

• MeSH
• buňky A549 MeSH
• dioxiny toxicita   MeSH
• druhová specificita MeSH
• hlodavci MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• myši MeSH
• plíce účinky léků   metabolismus   patologie   MeSH
• potkani Sprague-Dawley MeSH
• testy akutní toxicity metody   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

This article deals with the issue of Relative Age Effect (RAE), which enables the exploration of differences and links between the expected and observed distribution of birth date of athletes based on their date of birth. It is expected that into the elite choice are chosen athletes, who were born in the beginning of the year. Therefore, athletes born in last months of year are disadvantaged. In this article, RAE was tes-ted by the means of chi-squared test in Goodness-of-fit test and Kolmogorov-Smirnov test. Afterwards, Cramer’s V was used for more accurate estimation of a potency of the association between expected and observed distribution. By the usage of methods previously mentioned it was found out that in selected sport clubs, the results of RAE are not statistically confirmed, however, different connections, which cannot be left unnoticed, were observed. In the conclusion, there is stated that even though it is not obvious on the fleeting glance, the junior category in more influenced by RAE than the senior category. This fact is as such affected also by the nature of shotgun shooting, it emphasizes overall physical condition and physique rather than separate physical and age details of a shooter.

• Klíčová slova
• střelba,
• MeSH
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• sportovci * statistika a číselné údaje   MeSH
• střelné zbraně MeSH
• věkové faktory * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Geografické názvy
• Česká republika MeSH

INTRODUCTION: The emergence and spread of antibiotic resistance among pathogenic bacteria drives the search for alternative antimicrobial therapies. Bacteriocins represent a potential alternative to antibiotic treatment. In contrast to antibiotics, bacteriocins are peptides or proteins that have relatively narrow spectra of antibacterial activities and are produced by a wide range of bacterial species. Bacteriocins of Escherichia coli are historically classified as microcins and colicins, and, until now, more than 30 different bacteriocin types have been identified and characterized. AREAS COVERED: We performed bibliographical searches of online databases to review the literature regarding bacteriocins produced by E. coli with respect to their occurrence, bacteriocin role in bacterial colonization and pathogenicity, and application of their antimicrobial effect. EXPERT OPINION: The potential use of bacteriocins for applications in human and animal medicine and the food industry includes (i) the use of bacteriocin-producing probiotic strains, (ii) recombinant production in plants and application in food, and (iii) application of purified bacteriocins.

• MeSH
• antibakteriální látky biosyntéza   izolace a purifikace   farmakologie   MeSH
• bakteriociny biosyntéza   izolace a purifikace   farmakologie   MeSH
• Escherichia coli metabolismus   MeSH
• koliciny biosyntéza   izolace a purifikace   farmakologie   MeSH
• lidé MeSH
• probiotika farmakologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

The neuroprotective effects of a newly developed oxime K203 and currently available oximes (obidoxime, HI-6) in combination with atropine in rats poisoned with sarin were studied. The sarin-induced neurotoxicity was monitored using a functional observatory battery at 2 hr after sarin challenge. The results indicate that the potency of a novel bispyridinium oxime K203 to counteract sarin-induced neurotoxicity is relatively low and roughly corresponds to the neuroprotective efficacy of obidoxime. Among tested oximes, the oxime HI-6 seems to be significanlty more efficacious to counteract acute neurotoxicity of sarin than commonly used obidoxime and a newly developed oxime K203. Thus, the oxime K203 does not provide any beneficial effect for the antidotal treatment of acute poisoning with sarin in comparison with the oxime HI-6 that should be considered to be the best oxime for antidotal treatment of acute sarin poisonings.

• MeSH
• antagonisté muskarinových receptorů terapeutické užití   MeSH
• antidota škodlivé účinky   terapeutické užití   MeSH
• atropin terapeutické užití   MeSH
• autonomní nervový systém účinky léků   patofyziologie   MeSH
• chemické bojové látky chemie   toxicita   MeSH
• cholinesterasové inhibitory chemie   toxicita   MeSH
• kombinovaná farmakoterapie MeSH
• krysa rodu rattus MeSH
• LD50 MeSH
• neurony účinky léků   MeSH
• neurotoxické syndromy farmakoterapie   patofyziologie   MeSH
• obidoxim chlorid škodlivé účinky   terapeutické užití   MeSH
• oximy škodlivé účinky   terapeutické užití   MeSH
• potkani Wistar MeSH
• psychomotorický výkon účinky léků   MeSH
• pyridinové sloučeniny škodlivé účinky   terapeutické užití   MeSH
• reaktivátory cholinesterasy škodlivé účinky   terapeutické užití   MeSH
• sarin antagonisté a inhibitory   toxicita   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Geografické názvy
• Česká republika MeSH

BACKGROUND: Guidelines suggest that "upstream" P2Y12 receptor antagonists should be considered in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). HYPOTHESIS: Early use of ticagrelor in patients managed with an invasive strategy would be more effective than clopidogrel because of its more rapid onset of action and greater potency. METHODS: In the PLATO trial, 6792 NSTE-ACS patients were randomized to ticagrelor or clopidogrel (started prior to angiography) and underwent angiography within 72 hours of randomization. We compared efficacy and safety outcomes of ticagrelor vs clopidogrel as a function of "early" (<3h) vs "late" (≥3h) time to angiography. Adjusted Cox proportional hazards models evaluated interaction between randomized treatment and time from randomization to angiography on subsequent outcomes. RESULTS: Overall, a benefit of ticagrelor vs clopidogrel for cardiovascular death/myocardial infarction/stroke was seen at day 7 (hazard ratio [HR]: 0.67, P = 0.002), day 30 (HR: 0.81, P = 0.042), and 1 year (HR: 0.80, P = 0.0045). There were no significant interactions in the <3h vs ≥3h groups at any timepoint. For major bleeding, overall there was no significant increase (HR: 1.04, 95% confidence interval: 0.85-1.27); but there was a significant interaction with no difference between ticagrelor and clopidogrel in the early group (HR: 0.79), but higher bleeding risk with ticagrelor in the late angiography group, at 7 days (HR: 1.51, Pint = 0.002). Patterns were similar at 30 days and 1 year. CONCLUSIONS: The benefit of ticagrelor over clopidogrel was consistent in those undergoing early and late angiography, supporting upstream use of ticagrelor.

• MeSH
• adenosin aplikace a dávkování   analogy a deriváty   MeSH
• akutní koronární syndrom diagnóza   patofyziologie   terapie   MeSH
• antagonisté purinergních receptorů P2Y aplikace a dávkování   MeSH
• časové faktory MeSH
• dvojitá slepá metoda MeSH
• elektrokardiografie účinky léků   MeSH
• inhibitory agregace trombocytů aplikace a dávkování   MeSH
• koronární angiografie MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• revaskularizace myokardu * MeSH
• senioři MeSH
• tiklopidin aplikace a dávkování   analogy a deriváty   MeSH
• výsledek terapie MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

• MeSH
• algoritmy MeSH
• cytogenetické vyšetření MeSH
• látky znečišťující vzduch v pracovním prostředí MeSH
• lidé MeSH
• lymfocyty chemie   MeSH
• nádory prevence a kontrola   MeSH
• nemoc MeSH
• pracovní expozice MeSH
• pracovní lékařství zákonodárství a právo   MeSH
• riziko MeSH
• testy genotoxicity MeSH
• testy karcinogenity MeSH
• xenobiotika metabolismus   MeSH
• Check Tag
• lidé MeSH

AKR1C3 (also known as 17beta-hydroxysteroid dehydrogenase type 5 or 3alpha-hydroxysteroid dehydrogenase type 2) functions as a 3-keto, 17-keto and 20-ketosteroid reductase and as a 3alpha-, 17beta- and 20alpha-hydroxysteroid oxidase. Relatively high mRNA expression of AKR1C3 was found in human prostate and mammary gland where it is implicated in regulating ligand access to the androgen and estrogen receptor, respectively. AKR1C3 is an interesting target for the development of agents for treating hormone-dependent forms of cancer like prostate cancer, breast cancer, and endometrial cancer. However, only a few clinically promising and selective inhibitors have been reported so far. Very potent inhibitors of AKR1C3 are the non-steroidal anti-inflammatory drugs, e.g. indomethacin or flufenamic acid. Also dietary phytoestrogens such as coumestrol, quercetin, and biochanin were reported to inhibit the enzyme in low micromolar concentrations. In this study, some dietary flavonoids and other phenolic compounds were tested for their ability to specifically inhibit AKR1C3. Carbonyl reduction of the anticancer drug oracin, which is a very good substrate for AKR1C3 and which could be well monitored by a sensitive HPLC system with fluorescence detection, was employed to determine the inhibitory potency of the compounds. Our results reveal that AKR1C3 could be potentially un-competitively inhibited by 2'-hydroxyflavanone, whose IC(50) value of 300nM is clinically promising. Moreover, since the inhibition is selective towards AKR1C3, 2'-hydroxyflavanone could be useful for treating or preventing hormone-dependent malignancies like prostate and breast cancer.

• MeSH
• 3-hydroxysteroid dehydrogenasy antagonisté a inhibitory   genetika   izolace a purifikace   metabolismus   MeSH
• dieta MeSH
• DNA primery MeSH
• financování organizované MeSH
• flavonoidy aplikace a dávkování   farmakologie   MeSH
• fluorescenční spektrometrie MeSH
• hydroxyprostaglandindehydrogenasy antagonisté a inhibitory   genetika   izolace a purifikace   metabolismus   MeSH
• klonování DNA MeSH
• lidé MeSH
• rekombinantní proteiny antagonisté a inhibitory   genetika   izolace a purifikace   metabolismus   MeSH
• sekvence nukleotidů MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Check Tag
• lidé MeSH

Compounds with estrogenic potencies and their adverse effects in surface waters have received much attention. Both anthropogenic and natural compounds contribute to overall estrogenic activity in freshwaters. Recently, estrogenic potencies were also found to be associated with cyanobacteria and their blooms in surface waters. The present study developed and compared the solid phase extraction and LC-MS/MS analytical approaches for determination of phytoestrogens (8 flavonoids - biochanin A, coumestrol, daidzein, equol, formononetin, genistein, naringenin, apigenin - and 5 sterols - ergosterol, β-sitosterol, stigmasterol, campesterol, brassicasterol) and cholesterol in water. The method was used for analyses of samples collected in stagnant water bodies dominated by different cyanobacterial species. Concentrations of individual flavonoids ranged from below the limit of detection to 3.58 ng/L. Sterols were present in higher amounts up to 2.25 μg/L. Biological potencies of these phytoestrogens in vitro were characterized using the hERα-HeLa-9903 cell line. The relative estrogenic potencies (compared to model estrogen - 17β-estradiol) of flavonoids ranged from 2.25E-05 to 1.26E-03 with coumestrol being the most potent. None of the sterols elicited estrogenic response in the used bioassay. Estrogenic activity was detected in collected field water samples (maximum effect corresponding to 2.07 ng/L of 17β-estradiol equivalents, transcriptional assay). At maximum phytoestrogens accounted for only 1.56 pg/L of 17β-estradiol equivalents, contributing maximally 8.5% of the total estrogenicity of the water samples. Other compounds therefore, most likely of anthropogenic origin such as steroid estrogens, are probably the major drivers of total estrogenic effects in these surface waters.

• MeSH
• chemické látky znečišťující vodu analýza   MeSH
• cholestadienoly MeSH
• cholesterol analogy a deriváty   MeSH
• estradiol analýza   MeSH
• estrogeny analýza   MeSH
• estron analýza   MeSH
• fytoestrogeny analýza   MeSH
• fytosteroly MeSH
• genistein analýza   MeSH
• HeLa buňky MeSH
• isoflavony analýza   MeSH
• lidé MeSH
• receptory pro estrogeny metabolismus   MeSH
• sinice účinky léků   metabolismus   MeSH
• sitosteroly analýza   MeSH
• sladká voda MeSH
• steroly analýza   MeSH
• tandemová hmotnostní spektrometrie MeSH
• voda MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The evidence to date on the relation between the risk of venous thromboembolic disease (VTE) and antipsychotic agents derives primarily from observational and case history studies. While an increased risk of VTE has been associated with first-generation low-potency antipsychotic agents, particularly clozapine, there appears to be a growing number of reports on the occurrence of this adverse reaction during the use of second-generation antipsychotics, such as risperidone and olanzapine. The highest risk of pathological blood clotting emerges during the first 3 months after initiation of treatment with the product. Potential etiopathogenetic factors leading to VTE during treatment with antipsychotic agents include sedation, obesity, elevation of antiphospholipid antibodies, increased platelet activation and aggregation, hyperhomocysteinemia, and hyperprolactinemia. Diagnoses of schizophrenia and/or bipolar affective disorder, as well as hospitalization or stress with sympathetic activation and elevation of catecholamine levels, have been reported as known prothrombogenic factors. The present article contains the new version of the guideline for the prevention of VTE in psychiatric patients with limited mobility. Further prospective studies are necessary to elucidate the biological mechanisms of the relations between antipsychotic agents and VTE.

• MeSH
• antipsychotika škodlivé účinky   MeSH
• lidé MeSH
• psychotické poruchy farmakoterapie   MeSH
• riziko MeSH
• žilní tromboembolie chemicky indukované   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH