A multi-residue UHPLC-MS/MS analytical method, previously developed for monitoring 52 pharmaceuticals in drinking water, was used to analyse these pharmaceuticals in wastewater originating from healthcare facilities in the Czech Republic. Furthermore, the methodology was expanded to include the evaluation of the effectiveness of drug removal in Czech wastewater treatment plants (WWTPs). Of the 18 wastewater samples analysed by the validated UHPLC-MS/MS, each sample contained at least one quantifiable analyte. This study reveals the prevalence of several different drugs; mean concentrations of 702 μg L-1 of iomeprol, 48.8 μg L-1 of iopromide, 29.9 μg L-1 of gabapentin, 42.0 μg L-1 of caffeine and 82.5 μg L-1 of paracetamol were present. An analysis of 20 samples from ten WWTPs revealed different removal efficiencies for different analytes. Paracetamol was present in the inflow samples of all ten WWTPs and its removal efficiency was 100%. Analytes such as caffeine, ketoprofen, naproxen or atenolol showed high removal efficiencies exceeding 80%. On the other hand, pharmaceuticals like furosemide, metoprolol, iomeprol, zolpidem and tramadol showed lower removal efficiencies. Four pharmaceuticals exhibited higher concentrations in WWTP effluents than in the influents, resulting in negative removal efficiencies: warfarin at -9.5%, indomethacin at -53%, trimethoprim at -54% and metronidazole at -110%. These comprehensive findings contribute valuable insights to the pharmaceutical landscape of wastewater from healthcare facilities and the varied removal efficiencies of Czech WWTPs, which together with the already published literature, gives a more complete picture of the burden on the aquatic environment.

• MeSH
• jopamidol analogy a deriváty   MeSH
• kofein MeSH
• kosmetické přípravky * MeSH
• léčivé přípravky MeSH
• lidé MeSH
• odpadní voda MeSH
• paracetamol * MeSH
• tandemová hmotnostní spektrometrie MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Cíle: Stanovit hodnotu náklonu subjektivní vizuální vertikály (SVV) u zdravých dobrovolníků a u pacientů s periferním vestibulárním syndromem pomocí speciálně upraveného kbelíku (SVV bucket test). Zhodnotit interindividuální opakovatelnost vyšetření u pacientů otoneurologické poradny. Metodika: Srovnáním výsledků měření lékaře a sestry u 153 pacientů otoneurologické poradny jsme hodnotili interindividuální reprodukovatelnost této metody. Dále byly porovnány výsledky 38 zdravých dobrovolníků a 42 pacientů s periferní vestibulární lézí. Výsledky: Zjistili jsme dobrou reprodukovatelnost vyšetření. Průměrná výchylka SVV u zdravých dobrovolníků byla většinou do 1°, nepřesáhla 2°. Při vyšetření pacientů s periferní vestibulární lézí byly zjištěny statisticky signifikantně větší výchylky subjektivní vizuální vertikály než u zdravých dobrovolníků (p <0,001). Výchylka se u pacientů v čase snižovala. Závěr: Vyšetření subjektivní vizuální vertikály pomocí upraveného kbelíku je levné, rychlé a reprodukovatelné. U zdravých osob nepřesahuje výchylka SVV 2°. U pacientů s akutní jednostrannou vestibulopatií je ve většině případů vyšší, ukazuje stranu léze, výchylka se snižuje v čase.

Objectives: To determine the tilt of subjective visual vertical (SVV) in healthy volunteers and in patients with peripheral vestibular syndrome by SVV bucket test. Evaluate the interindividual repeatability of the examination in patients of otoneurological clinic. Methodology: The results of SVV bucket test of 38 healthy volunteers and 42 patients with peripheral vestibulopathy were compared. We evaluated the interrater variability of the method by comparing the results of measurements of a doctor and a nurse in 153 patients of otoneurological clinic. Results: The average SVV in healthy volunteers was mostly less than 1°, not more than 2°. Significantly greater tilt of subjective visual verticals was observed in patients with peripheral vestibular lesion (p < 0.001). The tilt decreased over time. We found a good interindividual reproducibility of the examination. Conclusion: Examination of subjective visual vertical by the SVV bucket method is inexpensive, fast and repeatable. In healthy subjects, the tilt of SVV does not exceed 2°. It is higher in most patients with acute unilateral vestibulopathy, shows the side of the lesion, and decreases over time.

• Klíčová slova
• SVV bucket test,
• MeSH
• deformace percepce MeSH
• diagnostické techniky a postupy přístrojové vybavení   MeSH
• klinická studie jako téma MeSH
• lidé MeSH
• vestibulární aparát MeSH
• vnímání prostoru * MeSH
• zraková percepce MeSH
• Check Tag
• lidé MeSH

The aim of this study was to trace the dynamic changes of methicillin-resistant Staphylococcus aureus (MRSA) lineages in the local hospital in both the national and international context. We describe genotypic and phenotypic characterization of 62 non-duplicate MRSA isolates collected during 2010-2016 at University Hospital in Hradec Kralove, Czech Republic. The isolates were characterized by multilocus sequence typing (MLST), spa typing, and staphylococcal cassette chromosome mec typing (SCCmec typing). Eight different genotypes were described; ST225-t003-II (32/62, 52%), ST5-t002-II (13/62, 22%), and ST225-t014-II (12/62, 21%) were constantly detected over the 7-year follow-up period. The genotypes ST225-t151-II, ST225-t1282-II, ST225-t1623-II, ST78-t2832-II, and ST225-t8799-II occurred only once in the period reported. The majority of the strains, represented by ST225, belonged to clonal complex 5 (CC5).

• MeSH
• antibakteriální látky farmakologie   MeSH
• bakteriemie epidemiologie   mikrobiologie   MeSH
• dítě MeSH
• dospělí MeSH
• fenotyp MeSH
• genotyp MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• methicilin rezistentní Staphylococcus aureus klasifikace   účinky léků   izolace a purifikace   MeSH
• mikrobiální testy citlivosti MeSH
• mladiství MeSH
• mladý dospělý MeSH
• multilokusová sekvenční typizace MeSH
• nemocnice univerzitní MeSH
• předškolní dítě MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stafylokokové infekce epidemiologie   MeSH
• techniky typizace bakterií MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Glioblastoma multiforme (GBM) represents approximately 60% of all brain tumors in adults. This malignancy shows a high biological and genetic heterogeneity associated with exceptional aggressiveness, leading to a poor survival of patients. This review provides a summary of the basic biology of GBM cells with emphasis on cell cycle and cytoskeletal apparatus of these cells, in particular microtubules. Their involvement in the important oncosuppressive process called mitotic catastrophe will next be discussed along with select examples of microtubule-targeting agents, which are currently explored in this respect such as benzimidazole carbamate compounds. Select microtubule-targeting agents, in particular benzimidazole carbamates, induce G2/M cell cycle arrest and mitotic catastrophe in tumor cells including GBM, resulting in phenotypically variable cell fates such as mitotic death or mitotic slippage with subsequent cell demise or permanent arrest leading to senescence. Their effect is coupled with low toxicity in normal cells and not developed chemoresistance. Given the lack of efficient cytostatics or modern molecular target-specific compounds in the treatment of GBM, drugs inducing mitotic catastrophe might offer a new, efficient alternative to the existing clinical management of this at present incurable malignancy.

• MeSH
• glioblastom * metabolismus   mortalita   terapie   MeSH
• kontrolní body fáze G2 buněčného cyklu * MeSH
• kontrolní body M fáze buněčného cyklu * MeSH
• lidé MeSH
• mitóza * MeSH
• nádory mozku * metabolismus   mortalita   patologie   terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

INTRODUCTION: Moderate and high levels of anticardiolipin antibodies (aCL), especially in the setting of the antiphospholipid syndrome, are associated with adverse obstetric outcomes. However, the clinical relevance of low aCL levels (<40 MPL/GPL units) is still a matter of debate. The aim of the study was to evaluate obstetric outcomes in pregnancies with low immunoglobulin M (IgM) and/or immunoglobulin G (IgG) aCL positivity. The association between low aCL positivity and maternal baseline characteristics was also studied. MATERIAL AND METHODS: The retrospective monocentric cohort study of prospectively collected data involved a total 3047 singleton pregnancies that underwent the first-trimester screening involving an aCL test and delivered on site. Obstetric outcomes were compared between the low-titer aCL group (IgM ≥7 MPL units and <40 MPL units and/or IgG ≥10 GPL units and <40 GPL units) and the aCL negative group (IgM <7 MPL units and IgG <10 GPL units, reference group). In addition, obstetric outcomes were evaluated with regard to the antibody isotype: IgM-positive group (IgM <40 MPL units, IgG negative) and IgG-positive group (IgG <40 GPL units, IgM negative or <40 MPL units). RESULTS: Overall, the occurrence of pregnancy-related complications was significantly higher (27.91% vs. 19.32%, p = 0.034) in the low-titer aCL group. Concerning the antibody isotype, a higher rate of pregnancy-related complications was observed in the IgG-positive group (54.55% vs. 19.32%, p = 0.001), but not in the IgM-positive group (22.43% vs. 19.32%, p = 0.454). The stillbirth rate did not reach statistical significance. Low-titer aCL pregnancies were more frequently of advanced maternal age (p < 0.001), suffered from autoimmune diseases (p < 0.001), chronic hypertension (p = 0.040), and hereditary thrombophilia (p = 0.040). In addition, they had more often a positive history of stillbirth (p < 0.001), underwent conception via assisted reproductive technologies (p < 0.001), were administered low-dose aspirin (p < 0.001), low-molecular-weight heparin (p = 0.018) and immunomodulatory drugs (p < 0.001), and delivered earlier (p = 0.018). CONCLUSIONS: Even low aCL levels are associated with a higher incidence of pregnancy-related complications, but only in the case of IgG antibody isotype presence. Screening for aCL in the first trimester has some prognostic value, but further studies are needed to determine whether its potential implementation into routine clinical practice would improve antenatal care.

• MeSH
• antifosfolipidový syndrom krev   MeSH
• antikardiolipinové protilátky * krev   MeSH
• dospělí MeSH
• imunoglobulin G krev   MeSH
• imunoglobulin M krev   MeSH
• kohortové studie MeSH
• komplikace těhotenství * krev   imunologie   epidemiologie   MeSH
• lidé MeSH
• retrospektivní studie MeSH
• těhotenství MeSH
• výsledek těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Riociguat is novel antihypertensive drug for treatment of pulmonary hypertension. As such, it is still being tested in many clinical and pharmacokinetic trials. Existing methods that determine serum riociguat and desmethylriociguat (DMR) are based solely on liquid chromatography with mass spectrometry. Therefore, we present a novel capillary electrophoresis with mass spectrometry method (CE-MS) for their determination in human serum as alternative method for ongoing trials. Complete resolution of both analytes was achieved by means of pH optimization of ammonium formate background electrolytes that are fully compatible with ESI/MS detection. Simple liquid-liquid extraction was used as sample pretreatment. The calibration dependence of the method was linear (in the range of 10-1000 ng/mL), with adequate accuracy (90.1-114.9%) and precision (13.4%). LOD and LOQ were arbitrarily set at 10 ng/mL for both analytes. Clinical applicability was validated using serum samples from patients treated with riociguat in pharmacokinetic study and the results corresponded with reference HPLC-MS/MS values. Capillary electrophoresis proved to be sensitive and selective tool for the analysis of riociguat and DMR.

• MeSH
• elektroforéza kapilární metody   MeSH
• elektrolyty MeSH
• extrakce kapalina-kapalina MeSH
• hmotnostní spektrometrie s elektrosprejovou ionizací metody   MeSH
• lidé MeSH
• limita detekce MeSH
• lineární modely MeSH
• pyrazoly krev   chemie   izolace a purifikace   farmakokinetika   MeSH
• pyrimidiny krev   chemie   izolace a purifikace   farmakokinetika   MeSH
• reprodukovatelnost výsledků MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Mental activity in sleep often involves visual and auditory content. Chemosensory (olfactory and gustatory) experiences are less common and underexplored. The aim of the study was to identify olfaction-related factors that may affect the occurrence of chemosensory dream content. Specifically, we investigated the effects of all-night exposure to an ambient odour, participants' appraisal of their current olfactory environment, their general propensity to notice odours and act on them (i.e., odour awareness), and their olfactory acuity. Sixty pre-screened healthy young adults underwent olfactory assessment, completed a measure of odour awareness, and spent three nights in weekly intervals in a sleep laboratory. The purpose of the first visit was to adapt to the experimental setting. On the second visit, half of them were exposed to the smell of vanillin or thioglycolic acid and the other half to an odourless control condition. On the third visit, they received control or stimulation in a balanced order. On each visit, data were collected twice: once from the first rapid eye movement (REM) stage that occurred after 3 a.m., and then shortly before getting up, usually from a non-REM stage. Participants were asked to report the presence of sensory dream content and to assess their current olfactory environment. Neither exposure, nor participants' assessments of the ambient odour, or olfactory acuity affected reports of chemosensory dream content but they were more frequent in individuals with greater odour awareness. This finding may have implications for treatment when such experiences become unwanted or bothersome.

• Publikační typ
• časopisecké články MeSH

Adiponectin has several beneficial properties, namely, on the level of glucose metabolism, but paradoxically, its high concentrations were associated with increased mortality. We aimed to clarify the impact of high serum adiponectin on mortality and morbidity in patients with stable coronary artery heart disease (CAD). A total of 973 patients after myocardial infarction and/or coronary revascularization were followed in a prospective cohort study. All-cause and cardiovascular (CV) death, non-fatal cardiovascular events, and hospitalizations for heart failure (HF) were registered as outcomes. High serum adiponectin levels (≥8.58 ng/ml, i. e., above median) were independently associated with increased risk of 5-year all-cause, CV mortality or HF [with HRR 1.57 (95% CI: 1.07-2.30), 1.74 (95% CI: 1.08-2.81) or 1.94 (95% CI: 1.20-3.12), respectively] when adjusted just for conventional risk factors. However, its significance disappeared if brain natriuretic peptide (BNP) was included in a regression model. In line with this, we observed strong collinearity of adiponectin and BNP. Additionally, major adverse cardiovascular event (i. e., CV death, non-fatal myocardial infarction or stroke, coronary revascularization) incidence risk was not associated with high adiponectin. In conclusion, the observed inverse association between adiponectin concentrations and mortality risk seems to be attributable to concomitantly increased BNP, rather than high adiponectin being a causal factor.

• MeSH
• adiponektin krev   MeSH
• biologické markery krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• morbidita MeSH
• následné studie MeSH
• nemoci koronárních tepen krev   epidemiologie   genetika   mortalita   MeSH
• prognóza MeSH
• prospektivní studie MeSH
• průřezové studie MeSH
• rizikové faktory MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Cannabis/cannabinoids are widely used for recreational and therapy purposes, but their risks are largely disregarded. However, cannabinoid-associated use disorders and dependence are alarmingly increasing and an effective treatment is lacking. Recently, the growth hormone secretagogue receptor (GHSR1A) antagonism was proposed as a promising mechanism for drug addiction therapy. However, the role of GHS-R1A and its endogenous ligand ghrelin in cannabinoid abuse remains unclear. Therefore, the aim of our study was to investigate whether the GHS-R1A antagonist JMV2959 could reduce the tetrahydrocannabinol (THC)-induced conditioned place preference (CPP) and behavioral stimulation, the WIN55,212-2 intravenous self-administration (IVSA), and the tendency to relapse. Following an ongoing WIN55,212-2 self-administration, JMV2959 3 mg/kg was administered intraperitoneally 20 min before three consequent daily 120-min IVSA sessions under a fixed ratio FR1, which significantly reduced the number of the active lever-pressing, the number of infusions, and the cannabinoid intake. Pretreatment with JMV2959 suggested reduction of the WIN55,212-2-seeking/relapse-like behavior tested in rats on the twelfth day of the forced abstinence period. On the contrary, pretreatment with ghrelin significantly increased the cannabinoid IVSA as well as enhanced the relapse-like behavior. Co-administration of ghrelin with JMV2959 abolished/reduced the significant efficacy of the GHS-R1A antagonist in the cannabinoid IVSA. Pretreatment with JMV2959 significantly and dose-dependently reduced the manifestation of THC-induced CPP. The THC-CPP development was reduced after the simultaneous administration of JMV2959 with THC during conditioning. JMV2959 also significantly reduced the THC-induced behavioral stimulation in the LABORAS cage. Our findings suggest that GHS-R1A importantly participates in the rewarding/reinforcing effects of cannabinoids.

• MeSH
• autoaplikace MeSH
• chování zvířat účinky léků   MeSH
• glycin analogy a deriváty   farmakologie   MeSH
• intravenózní podání MeSH
• kanabinoidy aplikace a dávkování   farmakologie   MeSH
• krysa rodu rattus MeSH
• operantní podmiňování účinky léků   MeSH
• podmiňování (psychologie) účinky léků   MeSH
• posilování (psychologie) MeSH
• potkani Wistar MeSH
• receptory ghrelinu antagonisté a inhibitory   MeSH
• triazoly farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

The dietary intake of flavonoids seems to be inversely related to cardiovascular mortality. The consumption of isoflavonoids is increasing in the general population, especially due to the use of food supplements and a variety of isoflavonoid-rich foods. However, detailed studies on the vascular influence of individual pure isoflavonoids are mostly missing. For this study, 16 isoflavonoids were initially screened for their vasorelaxant properties on rat aortas. The 2 most potent of them, biochanin A and glycitein, were further tested for the mechanism of action on porcine coronary arteries. They both induced an endothelium independent vascular relaxation, with EC50 below 6 and 17 µM, respectively. Biochanin A, but not glycitein, was able to block the vasoconstriction caused by KCl, CaCl2, serotonin, and U46619 in a dose-dependent manner. Another series of experiments suggested that the major mechanism of action of biochanin A was the inhibition of L-type calcium channels. Moreover, biochanin A in relatively small concentrations (2 - 4 µM) interfered with the cGMP, but not cAMP, pathway in isolated coronary arteries. These results indicate that some isoflavonoids, in particular biochanin A, are able to have vasodilatory effects in micromolar concentrations, which is of potential clinical interest for the management of cardiovascular pathologies.

• MeSH
• cévní endotel MeSH
• genistein MeSH
• isoflavony * MeSH
• koronární cévy MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• prasata MeSH
• vápník MeSH
• vápníkové kanály * MeSH
• vazodilatace MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH