The approaches to matrix effects determination and reduction in ultra-high performance supercritical fluid chromatography with mass spectrometry detection have been evaluated in this study using different sample preparation methods and investigation of different calibration models. Five sample preparation methods, including protein precipitation, liquid-liquid extraction, supported liquid extraction, and solid phase extraction based on both "bind and elute" and "interferent removal" modes, were optimized with an emphasis on the matrix effects and recovery of 8 forms of vitamin E, including α-, β-, γ-, and δ-tocopherols and tocotrienols, from plasma. The matrix effect evaluation included the use and comparison of external and internal calibration using three models, i.e., least square with no transformation and no weighting (1/x0), with 1/x2 weighting, and with logarithmic transformation. The calibration model with logarithmic transformation provided the lowest %-errors and the best fits. Moreover, the type of the calibration model significantly affected not only the fit of the data but also the matrix effects when evaluating them based on the comparison of calibration curve slopes. Indeed, based on the used calibration model, the matrix effects calculated from calibration slopes ranged from +92% to - 72% for α-tocopherol and from -77% to +19% in the case of δ-tocotrienol. Thus, it was crucial to calculate the matrix effect by Matuszewski's post-extraction approach at six concentration levels. Indeed, a strong concentration dependence was observed for all optimized sample preparation methods, even if the stable isotopically labelled internal standards (SIL-IS) were used for compensation. The significant differences between individual concentration levels and compounds were observed, even when the tested calibration range covered only one order of magnitude. In methods with wider calibration ranges, the inappropriate use of calibration slope comparison instead of the post-extraction addition approach could result in false negative results of matrix effects. In the selected example of vitamin E, solid-phase extraction was the least affected by matrix effects when used in interferent removal mode, but supported liquid extraction resulted in the highest recoveries. We showed that the calibration model, the use of a SIL-IS, and the analyte concentration level played a crucial role in the matrix effects. Moreover, the matrix effects can significantly differ for compounds with similar physicochemical properties and close retention times. Thus, in all bioanalytical applications, where different analytes are typically determined in one analytical run, it is necessary to carefully select the data processing in addition to the method for the sample preparation, SIL-IS, and chromatography.

• MeSH
• extrakce na pevné fázi metody   MeSH
• hmotnostní spektrometrie * metody   MeSH
• kalibrace MeSH
• lidé MeSH
• superkritická fluidní chromatografie * metody   MeSH
• vitamin E * krev   analýza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Indikace vhodné terapie u pacientů s karcinomem plic je v dnešní době založena na precizní molekulární charakteristice jejich tumorů. Karcinom plic je jedním z nejlépe popsaných solidních nádorů. V současnosti jsou v rámci běžné klinické praxe již k dispozici metody, které dokážou poměrně rychle, přesně a i finančně relativně výhodně analyzovat desítky genů a umožnit tak vytvoření komplexní molekulární charakteristiky nádoru. Na základě toho je možné pacientovi ušít léčbu přesně na míru a dosáhnout tak i s metastatickým onemocněním dlouhodobého a kvalitního přežití. Nové technologie přinášejí stále více informací a převést je do nejlepšího klinického benefitu pro pacienta může být náročné. Zde nachází své uplatnění multidisciplinární přístup v podobě molekulárního tumor boardu. Jeho rolí je snaha o indikaci vhodné terapie na základě zjištěné genetické alterace. Dnes máme k dispozici desítky cílených preparátů a objevují se nové léčebné možnosti i u doposud neovlivnitelných genetických alterací.

Nowadays, selection of appropriate therapy in patients with lung cancer is based on comprehensive molecular characteristics of their tumors. On molecular level, lung cancer is one of the best described solid tumors. Currently, there are already methods in routine clinical practice that enable a relatively quick, accurate and cost-effective analysis of dozens of genes and thus make it possible to determine a complex molecular characteristic of a tumor. This creates new possibilities to tailor the treatment to the patients to achieve long-term survival with a good quality of life. New technologies bring more and more information and to transform it into the best clinical benefit for the patient can be challenging. This is a place for the multidisciplinary approach in the form of a molecular tumor board. Its role is to try to indicate appropriate therapy based on the identified genetic alteration. Today, dozens of targeted drugs are available and new treatment options are emerging even for genetic alterations, which until now seemed to be undruggable.

• MeSH
• cílená molekulární terapie metody   MeSH
• diagnostické techniky molekulární metody   MeSH
• individualizovaná medicína metody   MeSH
• lidé MeSH
• nádory plic * diagnóza   terapie   MeSH
• nemalobuněčný karcinom plic * diagnóza   terapie   MeSH
• protokoly protinádorové léčby MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

The remarkably diverse affinity of alginate (ALG) macromolecules for polyvalent metal ions makes cross-linked alginate gels an outstanding biomaterial. Surprisingly, however, very little is known about their interactions and structural transformations in physiological environments. To bridge this gap, we prepared a set of ALG gels cross-linked by various ions and monitored their structural changes at different media simulating gastric and intestinal fluids and cellular environments. For these studies, we used multinuclear solid-state NMR (ss-NMR) spectroscopy, which revealed a range of competitive ion-exchange and interconversion reactions, the rate of which strongly depended on the nature of the cross-linking metal ions. Depending on the environment, ALG chains adopted different forms, such as acidic (hydro)gels stabilized by strong hydrogen bonds, and/or weakly cross-linked Na/H-gels. Simultaneously, the exchanged polyvalent ions extensively interacted with the environment even forming in some cases insoluble phosphate microdomains directly deposited in the ALG bead matrix. The extent of the transformations and incorporation of secondary phases into the alginate beads followed the size and electronegativity of the cross-linking ions. Overall, the applied combination of various macroscopic and biological tests with multinuclear ss-NMR revealed a complex pathway of alginate beads transformations in physiological environments.

• MeSH
• algináty chemie   farmakologie   MeSH
• biokompatibilní materiály chemie   farmakologie   MeSH
• buněčné mikroprostředí účinky léků   MeSH
• gely chemie   farmakologie   MeSH
• kovy chemie   MeSH
• lidé MeSH
• magnetická rezonanční spektroskopie MeSH
• reagencia zkříženě vázaná chemie   farmakologie   MeSH
• vodíková vazba účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• alergologie a imunologie MeSH
• imunitní systém MeSH
• Publikační typ
• učebnice MeSH

• Konspekt
• Patologie. Klinická medicína
• Učební osnovy. Vyučovací předměty. Učebnice
• NLK Obory
• alergologie a imunologie

ISCO using activated sodium persulphate is a widely used technology for treating chlorinated solvent source zones. In sensitive areas, however, high groundwater sulphate concentrations following treatment may be a drawback. In situ biogeochemical transformation, a technology that degrades contaminants via reduced iron minerals formed by microbial activity, offers a potential solution for such sites, the bioreduction of sulphate and production of iron sulphides that abiotically degrade chlorinated ethenes acting as a secondary technology following ISCO. This study assesses this approach in the field using hydrochemical and molecular tools, solid phase analysis and geochemical modelling. Following a neutralisation and bioaugmentation, favourable conditions for iron- and sulphate-reducers were created, resulting in a remarkable increase in their relative abundance. The abundance of dechlorinating bacteria (Dehalococcoides mccartyi, Dehalobacter sp. and Desulfitobacterium spp.) remained low throughout this process. The activity of iron- and sulphate-reducers was further stimulated through application of magnetite plus starch and microiron plus starch, resulting in an increase in ferrous iron concentration (from

• MeSH
• chemické látky znečišťující vodu analýza   metabolismus   MeSH
• chlor metabolismus   MeSH
• Chloroflexi metabolismus   MeSH
• čištění vody metody   MeSH
• Desulfitobacterium metabolismus   MeSH
• ethyleny metabolismus   MeSH
• halogenace MeSH
• oxidace-redukce MeSH
• Peptococcaceae metabolismus   MeSH
• podzemní voda analýza   chemie   mikrobiologie   MeSH
• regenerace a remediace životního prostředí metody   MeSH
• rozpouštědla metabolismus   MeSH
• sírany metabolismus   MeSH
• sloučeniny sodíku MeSH
• tetrachlorethylen analýza   metabolismus   MeSH
• trichlorethylen analýza   metabolismus   MeSH
• železo metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

Current studies reveal that the biomineralization of U(VI) by anaerobes normally produces nano-sized U(IV) minerals that can easily re-migrate/re-oxidize, while the biomineralization of U(VI) by aerobes has been constrained because the general mechanism has not yet been fully characterized. The biomineralization of U(VI) by Bacillus cereus 12-2 was investigated in this work. The maximum biosorption capability of intact cells was 448.68 mg U/g biomass (dry weight) at pH 5, while a decrease over 60% was induced when phosphate, amino, and especially carboxyl groups were shielded. X-ray diffraction, electron microscopy, and tracing the concentration of soluble intracellular U(VI) demonstrated that extracellular amorphous uranium particles can directly enter cells as solid, and about 10 nm-sized (NH4)(UO2)PO4·3H2O was formed subsequently. It was also revealed that the biosorption capability was not affected by a high uranium concentration, while biomineralization was inhibited, suggesting that a high concentration of heavy metals may inhibit the enzyme activity involved in biomineralization. Besides, U(VI) could trigger the overexpression of proteins with a molecular weight of 22 kD, including various phosphatases, kinases, and other enzymes that are related to metabolism and stimulus response, which may contribute to the intracellular transformation of U(VI) compounds from amorphous to crystalline phase. Taken together, the immobilization of U(VI) by B. cereus 12-2 contains two major steps: (1) fast immobilization of U(VI) on the cell surface as amorphous compounds, in which the carboxyl groups served as the predominant coordination functional groups and (2) transport of amorphous particles to cells directly and enzyme-related formation of uramphite.

• MeSH
• Bacillus cereus chemie   MeSH
• difrakce rentgenového záření metody   MeSH
• minerály chemie   MeSH
• uran chemie   MeSH
• Publikační typ
• časopisecké články MeSH

Gangliogliom patří do skupiny vzácných smíšených glioneurálních nádorů, které vykazují diferenciaci jak gliových buněk, tak neuronů (zralých ale dysmorfních). Podle některých teorií vznikají z prekurzorových kmenových buněk, kdy gliové elementy mohou maligně transformovat. Typicky se jedná o low grade gliom obsahující zřetelné gangliocytární elementy. Makroskopicky je nádor lokalizován obvykle povrchově a často expanduje do kortexu, obsahuje solidní i cystickou porci, kalcifikace, zřídka hemoragie a nekrózy. Mikroskopicky se jedná o směs dysplastických neuronálních buněk a gliálních elementů, nejčastěji astrocytů, které tvoří proliferující buňky tohoto tumoru. Biologické chování gangliogliomu je většinou méně agresivní než u „čistých“ gliových tumorů. Velmi vzácně gangliogliom progreduje do high grade gliálního tumoru vlivem dodatečných genetických alterací. Agresivní formy připomínají morfologicky maligní gliomy, ale imunohistochemicky je průkazná i neuronální diferenciace nádorových buněk. Gangliogliom v zobrazení magnetickou rezonancí je kortikálně uložená léze s dvěma typickými obrazy. Onkologická léčba anaplastického gangliogliomu není standardizována. Pro klinickou praxi jsou v literatuře dostupné pouze limitované informace o účinnosti onkologické terapie.

Ganglioglioma belongs to the group of rare mixed glioneural tumors, that grow from glial cells and neurons (mature but dysmorfic).According to some theories they arise from precursor stem cells, where glial cells can be malignantly transformed. Typicallyganglioglioma is a low grade glioma containing distinct gangliocytic elements. Macroscopically the tumor is localized on thesurface of the brain and often expands to the cortex; it contains both solid and cystic portions, calcifications, rarely hemorrhageand necrosis. Microscopically ganglioglioma consists of a mixture of dysplastic neuronal cells and glial cells, most commonlyastrocytes, which forms the proliferative pool of neoplastic tumor cells. The biological behaviour of ganglioglioma is generallyless aggressive compared to the „pure“ glial tumors. Rarely ganglioglioma progresses to the high grade glial tumor due to theadditional genetic alterations. Aggressive forms resemble morphologically malignant gliomas, but immunohistochemically alsosignificant neuronal differentiation of tumor cells is present. Ganglioglioma is the cortical lesion with two typical images in MRimaging. The oncological treatment of anaplastic ganglioglioma has no standard. Only limited informations about the effectivenessof the oncological therapy are available in the literature for clinicians.

• MeSH
• gangliogliom * diagnostické zobrazování   diagnóza   terapie   MeSH
• histologické techniky metody   MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• mladý dospělý MeSH
• mutace genetika   MeSH
• protokoly protinádorové léčby MeSH
• radiochirurgie metody   MeSH
• radioterapie metody   MeSH
• recidiva MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Procyanidins, contained in many products abundant in human diet, exhibit high biological activity. However, this activity has not been fully explained at cellular and molecular levels. In this study, we determine the mechanism of interaction of procyanidin B3 with model lipid membrane. This mechanism was established on the basis of changes induced by B3 in the physical properties of lipid bilayer. The changes were investigated using steady state and time-resolved fluorescence, DSC, and FTIR. We show that procyanidin B3 causes changes in the arrangement of the polar heads of lipids, order of their acyl chains and the main lipid phase transition temperature. Furthermore, its presence in the membrane leads to a reduction in membrane dipole potential. Procyanidin B3 is anchored to membrane via hydrogen bonds formed between its OH groups and the PO2- and CO groups of lipids, causing changes in both hydrophilic and hydrophobic regions of the membrane.

• MeSH
• 2-naftylamin analogy a deriváty   chemie   MeSH
• biflavonoidy chemie   MeSH
• diferenciální skenovací kalorimetrie MeSH
• dihydropyridiny chemie   MeSH
• dimyristoylfosfatidylcholin chemie   MeSH
• fluorescenční spektrometrie MeSH
• hydrofobní a hydrofilní interakce MeSH
• katechin chemie   MeSH
• laurany chemie   MeSH
• lipidové dvojvrstvy chemie   MeSH
• proantokyanidiny chemie   MeSH
• spektroskopie infračervená s Fourierovou transformací MeSH
• teplota MeSH
• termodynamika MeSH
• vodíková vazba MeSH
• změna skupenství MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Commercially available antibacterial semisolid preparations intended for topical application provide only short-term drug release. A sustained kinetics is possible by exploitation of a biodegradable polymer carrier. The purpose of this work is to formulate a mucoadhesive system with aciclovir (ACV) based on a solid molecular dispersion of this drug in poly(lactic-co-glycolic acid) branched on tripenterythritol (PLGA/T). The ACV incorporation into PLGA/T was carried out either by solvent method, or melting method, or plasticization method using various plasticizers. The drug-polymer miscibility, plasticizer efficiency and content of residual solvent were found out employing DSC. Viscosity was measured at the shear rate range from 0.10 to 10.00 s(-1) at three temperatures and data were analyzed by Newtonian model. The mucoadhesive properties were ascertained in the tensile test on a mucin substrate. The amount of ACV released was carried out in a wash-off dissolution test. The DSC results indicate a transformation of crystalline form of ACV into an amorphous dissolved in branched polyester carrier, and absence of methyl formate residuals in formulation. All the tested plasticizers are efficient at Tg depression and viscosity decrease. The non-conventional ethyl pyruvate possessing supportive anti-inflammatory activity was evaluated as the most suitable plasticizer. The ACV release was strongly dependent on the ethyl pyruvate concentration and lasted from 1 to 10 days. The formulated PLGA/T system with ACV exhibits increased adhesion to mucosal hydrophilic surfaces and prolonged ACV release controllable by degradation process and viscosity parameters.

• MeSH
• acyklovir aplikace a dávkování   chemie   MeSH
• biokompatibilní materiály chemie   MeSH
• časové faktory MeSH
• hydrofobní a hydrofilní interakce MeSH
• kyselina mléčná chemie   MeSH
• kyselina polyglykolová chemie   MeSH
• léky s prodlouženým účinkem MeSH
• povrchové vlastnosti MeSH
• uvolňování léčiv MeSH
• velikost částic MeSH
• změkčovadla aplikace a dávkování   chemie   MeSH
• Publikační typ
• časopisecké články MeSH

A series of anionic heavy lanthanide complexes, involving the N-salicylideneglycinato(2-) Schiff base ligand (salgly) and having the general formula K[Ln(salgly)₂(H₂O)₂]∙H₂O (1-6), where Ln stands for Gd, Tb, Dy, Ho, Er and Tm, was prepared using the one-pot template synthesis. The complexes were thoroughly characterized by elemental and Thermogravimetric/Differential Thermal Analyses (TG/DTA), Fourier Transform Infrared Spectroscopy (FT-IR), and photoluminescence spectroscopies, electrospray-ionization mass spectrometry, and their magnetic properties were studied by temperature-dependent dc magnetic measurements using the superconducting quantum interference device (SQUID). The X-ray structure of the terbium(III) complex (2), representing the unique structure between the lanthanide complexes of N-salicylideneamino acids, was determined. The results of spectral and structural studies revealed the isostructural nature of the prepared complexes, in which the lanthanide ion is octacoordinated by two O,N,O-donor salgly ligands and two aqua ligands. The analysis of magnetic data confirmed that the complexes behave as paramagnets obeying the Curie law. The results of photoluminescence spectral studies of the complexes showed the different origin in their luminescent properties between the solid state and solution. An antenna effect of the Schiff base ligand was observed in a powder form of the complex only, while it acts as a fluorophore in a solution.

• MeSH
• chemické modely MeSH
• fotochemické procesy MeSH
• glycin chemie   MeSH
• hmotnostní spektrometrie s elektrosprejovou ionizací MeSH
• komplexní sloučeniny chemie   MeSH
• krystalografie rentgenová MeSH
• kyselina salicylová chemie   MeSH
• lanthanoidy chemie   MeSH
• ligandy MeSH
• luminescentní proteiny chemie   MeSH
• luminiscence MeSH
• magnetismus MeSH
• prášky, zásypy, pudry MeSH
• spektroskopie infračervená s Fourierovou transformací MeSH
• teplota MeSH
• termogravimetrie MeSH
• vodíková vazba MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH