OBJECTIVE: Epidemiological research has shown that air pollution is associated with cardiovascular events, but little is known about short-term effects on blood pressure (BP) and heart rate (HR) in Serbian population. The present study assessed the short-term association between black smoke (BS) and sulphur dioxide (SO2) levels in urban air and the daily values of blood pressure and heart rate in 98 healthy nonsmoking female volunteers. METHODS: Generalized regression model was fitted controlling for temperature, relative humidity, air pressure, season, and the day of the week. RESULTS: There was no association between short-term air pollution exposure and BP and HR, the exposure showed a tendency toward a decrease of diastolic BP and HR, but with no statistical significance. CONCLUSION: The present findings did not support the conclusion that current levels of ambient BS and SO2 may have an effect on blood pressure and heart rate in women.

• MeSH
• časové faktory MeSH
• kouř analýza   MeSH
• krevní tlak fyziologie   MeSH
• lidé MeSH
• oxid siřičitý analýza   MeSH
• srdeční frekvence fyziologie   MeSH
• velkoměsta MeSH
• vystavení vlivu životního prostředí škodlivé účinky   statistika a číselné údaje   MeSH
• znečištění ovzduší škodlivé účinky   analýza   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Srbsko MeSH
• velkoměsta MeSH

Ambient ionization mass spectrometry allows for analysis of samples in their natural state, i.e., with no sample pre-treatment. It can be viewed as a fast, simple, and economical analysis, but its main disadvantages include a lower analytical performance due to the presence of complex sample matrix and the lack of chromatographic separation prior to the introduction of the sample into the mass spectrometer. Here we present an application of two ambient ionization mass spectrometry techniques, i.e., Desorption Atmospheric Pressure Photoionization and Dielectric Barrier Discharge Ionization, for the analysis of known Selective Androgen Receptor Modulators, which represent common compounds of abuse in professional and semiprofessional sport. Eight real samples of illegal food supplements, seized by the local law enforcement, were used to test the performance of the ambient mass spectrometry and the results were validated against a newly developed targeted LC-UV-MS/MS method performed in multiple reaction monitoring mode with an external calibration for each analyte. In order to decide whether or not the compound can be declared as present, we proposed a system of rules for the interpretation of the obtained spectra. The criteria are based on mass spectrum matching (5-10 ppm accuracy from the theoretical exact mass and a correct isotopic pattern), duration of the mass signal (three or five consecutive scans, depending on the instrumentation used), and intensity above the background noise (threefold increase in intensity and absolute intensity above 5E4 or 1E5, depending on the instrumentation). When applying these criteria, good agreement was found between the tested methods. Ambient ionization techniques were effective at detecting SARMs at pharmacologically relevant doses, i.e., approximately above 1 mg per capsule, although they may fail to detect lower levels or isomeric species. It is demonstrated that when adhering to a set of clear and consistent rules, ambient mass spectrometry can be employed as a qualitative technique for the screening of illegal SARMs with sufficient confidence and without the necessity to perform a regular LC-MS analysis.

• MeSH
• androgenní receptory * metabolismus   MeSH
• antagonisté androgenních receptorů analýza   MeSH
• chromatografie kapalinová metody   MeSH
• doping ve sportu prevence a kontrola   MeSH
• hmotnostní spektrometrie metody   MeSH
• lidé MeSH
• odhalování abúzu drog metody   MeSH
• potravní doplňky analýza   MeSH
• tandemová hmotnostní spektrometrie metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

RATIONALE: Hyphenation of atmospheric pressure chemical ionization (APCI) mass spectrometry with capillary and micro high-performance liquid chromatography (HPLC) is attractive for many applications, but reliable ion sources dedicated to these conditions are still missing. There are a number of aspects to consider when designing such an ion source, including the susceptibility of the ionization processes to ambient conditions. Here we discuss the importance of ion source housing for APCI at low flow rates. METHODS: Selected compounds dissolved in various solvents were used to study ionization reactions at 10 μL/min flow rate. APCI spectra were generated using the Ion Max-S source (Thermo Fisher Scientific) operated with or without the ion source housing. RESULTS: The APCI spectra of most compounds measured in the open and enclosed ion sources were markedly different. The differences were explained by water and oxygen molecules that entered the plasma region of the open ion source. Water tended to suppress charge transfer processes while oxygen diminished electron capture reactions and prevented the formation of acetonitrile-related radical cations useful for localizing double bonds in lipids. The effects associated with the ion source housing were significantly less important for compounds that are easy to protonate or deprotonate. CONCLUSIONS: The use of ion source housing prevented alternative ionization channels leading to unwanted or unexpected ions. Compared with the conventional flow rate mode (1 mL/min), the effects of ambient air components were significantly higher at 10 μL/min, emphasizing the need for ion source housing in APCI sources dedicated to low flow rates.

• Publikační typ
• časopisecké články MeSH

Bakteriálne infekcie kože a mäkkých tkanív zahŕňajú rozsiahlu problematiku a predstavujú najčastejšie vyskytujúce sa infekcie vo všetkých vekových skupinách. Obvykle ide o infekcie zmiešané vyvolané anaeróbnymi, mikroaerofilnými, fakultatívne anaeróbnymi a aeróbnymi baktériami. Pri patogenéze je možné v ložisku infekcie pozorovať prítomnosť aeróbnych baktérií, ktoré produktmi svojho metabolizmu a redukciou koncentrácie kyslíka umožnia pomnoženie striktne anaeróbnym patogénom. Úspešná terapia infekcií mäkkých tkanív je závislá od adekvátneho chirurgického prístupu, vhodnou antimikrobiálnou terapiou a adjuvantnej terapie infekcie mäkkých tkanív pomocou hyperbarickej oxygenoterapie (HBOT), t. j. dýchanie 100% kyslíka pod zvýšeným tlakom. V súčasnosti, aj napriek dostatočným empirickým znalostiam o benefitoch využitia HBOT pri liečbe infekcií mäkkých tkanív, neexistuje vhodný model pre detailnejšie štúdium interakcií organizmu a patogénov. Cieľom tohto projektu je vývoj in vitro modelu vhodného pre štúdium mechanizmov účinku antibiotík v kombinácii s HBOT, ako aj optimalizáciu používaných liečebných postupov.

Bacterial soft tissue infections represent the most common infections. Usually, they are caused by anaerobic, microaerophilic, facultative anaerobic and aerobic bacteria. In pathogenesis, a tissue is initially colonized by aerobic bacteria, which create a suitable environment for secondary colonization of anaerobic bacterial strains. Successful therapy of soft tissues infections consist of appropriate surgery treatment, targeted anti-microbial therapy and application of hyperbaric oxygen therapy (HBOT), i.e. breathing of pure oxygen under elevated ambient pressure. Nowadays, despite a lot of positive clinical evidence of HBOT in soft tissue infection treatment, no valid experimental model is established. The aim of our project was the development of an experimental model to study host-pathogen interaction during HBOT.

• MeSH
• antibakteriální látky * terapeutické užití   MeSH
• Bacteria klasifikace   účinky léků   MeSH
• bakteriální infekce farmakoterapie   terapie   MeSH
• hyperbarická oxygenace * MeSH
• infekce měkkých tkání * klasifikace   mikrobiologie   terapie   MeSH
• kombinovaná terapie MeSH
• lidé MeSH
• techniky in vitro MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

Vývoj inhibitorů SGLT2 (známých také jako glifloziny) navazoval na řadu dekád fyziologických výzkumů renálních funkcí, a zejména na identifikaci transportních molekul SGLT (sodium‑glucose cotransporter) ve tkáni ledvin v roce 1992. Ač byly inhibitory SGLT2 původně vyvíjeny jako antidiabetika, inhibice sodíko‑glukózového kotransportéru 2 přináší široké spektrum účinků na funkci ledvin, na homeostázu objemu plazmy i na celkový energetický metabolismus těla. U nemocných s diabetem 2. typu je při podávání inhibitorů SGLT2 snížení glykemie proporcionální výši původní hyperglykemie a glomerulární filtraci této glukózy. V klinických studiích byl při podávání inhibitorů SGLT2 pozorován pokles hodnoty HbA1c v rozsahu 7–10 mmol/l vs. placebo nezávisle na přidružené antidiabetické léčbě. Léčba inhibitory SGLT2 byla ve většině studií spojena s poklesem tělesné hmotnosti o 2–3 kg za šest měsíců podávání, což je podmíněno ztrátou tukové tkáně, a to i tuku v játrech a tuku viscerálního. Na úrovni ledvin vede léčba inhibitory SGLT2 k poklesu intraglomerulárního tlaku, který je společným jmenovatelem snížení progrese albuminurie a zpomalení poklesu renálních funkcí u léčených osob ve srovnání s placebem. Použití inhibitorů SGLT2 je spojeno i s poklesem systolického (o 4–6 mm Hg) i diastolického (o 1–2 mm Hg) tlaku, nicméně inhibitory SGLT‑2 zaujaly odbornou veřejnost především svou schopností snížit výskyt kardiovaskulárních příhod, zejména srdečního selhání. Výsledky metaanalýzy kardiovaskulárních studií s inhibitory SGLT2 svědčí o jejich mimořádném a statisticky „spolehlivém“ účinku na snížení počtu hospitalizací pro srdeční selhání (o 31 %) a na omezení progrese renálního postižení (o 45 %). Účinek inhibitorů SGLT‑2 na sdružený ukazatel manifestace aterosklerózy (IM, CMP a úmrtí z kardiovaskulárních příčin) se projevil signifikantním snížením o 11 %. Při léčbě inhibitory SGLT2 je nutné počítat s možností vzniku mykotických infekcí genitálu a s nízkým rizikem diabetické ketoacidózy. Při adekvátních opatřeních lze riziko těchto nežádoucích účinků snížit a v celkovém kontextu jasně převažují přínosy léčby, které v mezinárodních i národních doporučeních „posunuly” inhibitory SGLT2 na pozici druhé léčebné volby po metforminu u osob trpících diabetem 2. typu a kardiovaskulárním onemocněním (především srdečním selháním) nebo chronickým onemocněním ledvin.

Development of the SGLT2 inhibitor class (known also as the gliflozins) followed after several decades of physiologic research of renal functions and especially after the identification of transporter molecules (sodium‑glucose contransporter) in renal tissue in 1992. Although SGLT2 inhibitors were primarily developed as glucose‑lowering agents, inhibition of sodium‑glucose contransporter brings about pleiotropic effects on renal functions, plasma volume homeostasis and metabolic processes across the entire body. SGLT2 inhibitor therapy in type 2 diabetes reduces plasma glucose levels proprortional to the ambient glucose concentration and the glomerular filtration of this glucose. In clinical trials, SGLT2 inhibitors are associated with a reduction in HbA1c by 7–10 mmol/L vs. placebo, regardless of background therapy. Most studies assessing SGLT2 inhibitors treatment reported loss of 2–3 kg body weight over the initial 6 months of therapy, including reductions in steatosis and visceral adipose tissue. Looking into renal functions SGLT2 are associated with reduction of intraglomerular pressure that is a common denominator of reduced progression of albuminuria and slower decline in renal function when compared with placebo. Use of SGLT2 inhibitors cause lowering of systolic and diastolic blood pressure by 4–6 mmHg and 1–2 mmHg respectively, nevertheless SGLT2 inhibitors drew attention of scientific community especially by unprecedented reductions of cardiovascular events, particularly hospitalisation for heart failure. Results of meta‑analysis of cardiovascular outcome trials with SGLT2 inhibitors showed their greatest and most consistent effect on reducing the relative risk of hospitalisation for heart failure (31%) and of progression of renal disease (45%). Their effect on the composite atherosclerotic outcome of myocardial infarction, stroke or cardiovascular death was significant 11% reduction in relative risk. During treatment with SGLT2 inhibitors one should take into account possibility of development of genital mycotic infections or diabetic ketoacidosis. It is important that adequate measures can reduce the risk of these side effects and in overall assesment benefits clearly prevail risks of treatment. International and national Czech guidelines consider SGLT2 inhibitors as a suitable second agent add‑on metformin therapy in patients with type 2 diabetes and cardiovascular disease (particularly heart failure) or chronic kidney disease.

• MeSH
• amputace statistika a číselné údaje   MeSH
• diabetes mellitus 2. typu * farmakoterapie   MeSH
• fraktury kostí epidemiologie   chemicky indukované   MeSH
• glifloziny aplikace a dávkování   farmakokinetika   farmakologie   MeSH
• hodnoty glomerulární filtrace účinky léků   MeSH
• hypoglykemika MeSH
• kardiovaskulární nemoci prevence a kontrola   MeSH
• krevní tlak účinky léků   MeSH
• lidé MeSH
• nežádoucí účinky léčiv epidemiologie   etiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Among other side effects, administration of anticancer agents is accompanied by manifestations of gastrointestinal toxicity and disturbances of antioxidant balance. The monitoring of these toxic effects in clinical practice is impeded by a dearth of reliable laboratory methods. Therefore, a simple and rapid reversed-phase high-performance liquid chromatography procedure for selective and sensitive determination of retinol, a-tocopherol, and retinyl esters (retinyl-palmitate and retinyl-stearate) in blood serum has been developed and presented in this study. A Series 200 LC HPLC instrument from Perkin Elmer (Norwalk, USA) with diode-array detector (DAD) was used for the analysis. Separations of retinol, alpha-tocopherol, retinyl-palmitate, and retinyl-stearate were performed using a Chromolith Performance RP-18e, 100 x 4.6 mm monolithic column from Merck (Darmstadt, Germany). Gradient elution was used at a flow rate of 3 mL/min; the mobile phase was methanol-water (95:5, v/v) for 0-2.1 min and methanol-2-propanol (60:40, v/v) for 2.1-4.9 min. The total time of analysis was 6 min. The injection volume was 20 microL and the analysis was performed at ambient temperature. Detection of retinol, alpha-tocopherol, and retinyl esters was carried out at 325, 295, and 330 nm, respectively. For practical assessment of the method, the vitamin A absorption test was performed on seven healthy controls as well as on six patients with non-small cell lung carcinoma or head and neck carcinoma previously treated by chemotherapy and/or radiotherapy, six patients with rectal carcinoma before chemoradiotherapy, four patients with gastrointestinal stromal tumor (GIST) before treatment with imatinib, and a breast cancer patient with chemotherapy-induced diarrhea. Present data demonstrate the feasibility of large scale HPLC determination of vitamin E, vitamin A, and retinyl esters in human serum using a silica monolithic column, and this method may represent a valuable aid in the laboratory monitoring of the toxicity of anticancer therapy.

• MeSH
• absorpce MeSH
• časové faktory MeSH
• chromatografie metody   MeSH
• estery * analýza   krev   MeSH
• gastrointestinální stromální tumory farmakoterapie   MeSH
• kalibrace MeSH
• lidé MeSH
• monitorování léčiv * metody   MeSH
• piperaziny farmakologie   škodlivé účinky   MeSH
• protinádorové látky * farmakologie   škodlivé účinky   MeSH
• průjem chemicky indukované   MeSH
• pyrimidiny farmakologie   škodlivé účinky   MeSH
• reprodukovatelnost výsledků MeSH
• vitamin A * MeSH
• vysokoúčinná kapalinová chromatografie metody   přístrojové vybavení   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

A sensitive and accurate method utilizing ultrahigh performance liquid chromatography (U-HPLC) coupled to high resolution mass spectrometry based on orbitrap technology (orbitrapMS) for the analysis of nine 3-chloropropane-1,2-diol (3-MCPD) diesters in vegetable oils was developed. To remove the interfering triacylglycerols that induce strong matrix effects, a clean-up step on silica gel column was used. The quantitative analysis was performed with the use of deuterium-labeled internal standards. The lowest calibration levels estimated for the respective analytes ranged from 2 to 5 μg kg(-1). Good recovery values (89-120%) and repeatability (RSD 5-9%) was obtained at spiking levels of 2 and 10 mg kg(-1). As an alternative, a novel ambient desorption ionization technique, direct analysis in real time (DART), hyphenated with orbitrapMS, was employed for no separation, high-throughput, semi-quantitative screening of 3-MCPD diesters in samples obtained by chromatographic fractionation. Additionally, the levels of 3-MCPD diesters measured in reallife vegetable oil samples (palm oil, sunflower oil, rapeseed oil) using both methods are reported. Relatively good agreement of the data generated by U-HPLC-orbitrapMS and DART-orbitrapMS were observed. With regard to a low ionization yield achieved for 3-MCPD monoesters, the methods presented in this paper were not yet applicable for the analysis of these contaminants at the naturally occurring levels.

• MeSH
• estery analýza   MeSH
• glycerol analogy a deriváty   analýza   MeSH
• hmotnostní spektrometrie metody   MeSH
• oleje rostlin analýza   MeSH
• vysokoúčinná kapalinová chromatografie metody   MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH

The objective of the presented study was to develop and optimize a simple, high-throughput method for the control of 32 mycotoxins (Fusarium and Alternaria toxins, aflatoxins, ergot alkaloids, ochratoxins, and sterigmatocystin) in beer. Due to the broad range of their physicochemical properties, the sample preparation step was simplified as much as possible to avoid analyte losses. The addition of acetonitrile to beer samples enabled precipitation of abundant matrix components. The clean-up efficiency was controlled by ambient mass spectrometry employing a direct analysis in real time (DART) ion source. For determination of analytes, ultra-high-performance liquid chromatography hyphenated with high-resolution mass spectrometry utilizing an orbitrap (U-HPLC-orbitrapMS) or time-of-flight (TOFMS) technology was used. Because of significantly better detection capabilities of the orbitrap technology, the U-HPLC-orbitrapMS method was chosen as a determinative step and fully validated. To compensate matrix effects, matrix-matched calibration was employed. The lowest calibration levels for most of the target mycotoxins ranged from 1 to 8  µg  L(-1) beer and the recoveries of analytes were in range from 86 to 124%.

• MeSH
• acetonitrily chemie   MeSH
• Fusarium MeSH
• hmotnostní spektrometrie metody   MeSH
• kalibrace MeSH
• mykotoxiny analýza   izolace a purifikace   MeSH
• pivo analýza   MeSH
• reprodukovatelnost výsledků MeSH
• rychlé screeningové testy MeSH
• senzitivita a specificita MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• benzofurany MeSH
• dioxiny MeSH
• pracovní expozice MeSH
• vystavení vlivu životního prostředí MeSH

• Konspekt
• Veřejné zdraví a hygiena
• NLK Obory
• environmentální vědy
• NLK Publikační typ
• publikace WHO

• MeSH
• olovo škodlivé účinky   MeSH
• vystavení vlivu životního prostředí MeSH

• Konspekt
• Veřejné zdraví a hygiena
• NLK Obory
• environmentální vědy
• environmentální vědy
• NLK Publikační typ
• publikace WHO