Surface bioactivity has been under intensive study with reference to its use in medical implants. Our study is focused on coatings prepared from an electroactive material which can support bone cell adhesion. Until now, hydroxyapatite films have usually been utilized as a chemically-active surface agent. However, electrically-active films could set a new direction in hard tissue replacement. As a base for these films, it is necessary to prepare an intermediate film, which can serve as a suitable barrier against the possible diffusion of some allergens and toxic elements from the substrate. The intermediate film also improves the adaptation of the mechanical properties of the basic material to an electroactive film. The aim of our work was to select an implantable and biocompatible material for this intermediate film that is suitable for coating several widely-used materials, to check the possibility of preparing an electroactive film for use on a material of this type, and to characterize the structure and several mechanical properties of this intermediate film. TiNb was selected as the material for the intermediate film, because of its excellent chemical and mechanical properties. TiNb coatings were deposited by magnetron sputtering on various substrates, namely Ti, Ti6Al4V, stainless steel, and bulk TiNb (as standard), and important properties of the layers, e.g. surface morphology and surface roughness, crystalline structure, etc., were characterized by several methods (SEM, EBSD, X-ray diffraction, nanoindentation and roughness measurement). It was found that the structure and the mechanical properties of the TiNb layer depended significantly on the type of substrate. TiNb was then used as a substrate for depositing a ferroelectrically active material, e.g., BaTiO3, and the adhesion, viability and proliferation of human osteoblast-like Saos-2 cells on this system were studied. We found that the electroactive BaTiO3 film was not only non-cytotoxic (i.e. it did not affect the cell viability). It also enhanced the growth of Saos-2 cells in comparison with pure TiNb and with standard tissue culture polystyrene wells, and also in comparison with BaTiO3 films deposited on Ti, i.e. a material clinically used for implantation into the bone.

• MeSH
• adheziva MeSH
• difrakce rentgenového záření MeSH
• hydroxyapatit MeSH
• lidé MeSH
• osteoblasty MeSH
• povrchové vlastnosti MeSH
• protézy a implantáty MeSH
• slitiny chemie   MeSH
• testování materiálů MeSH
• titan MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Separation of biologically active peptides was performed on polybutadiene (PBD) and polystyrene (PS) reversed phases based on zirconium dioxide. ZrO2 as an alternative carrier to silicagel offers ion-exchange interactions, which are useful for separation of ionizable compounds. The parameters like buffer concentration and pH, the amount of organic modifier and temperature affected separation of nonapeptides. The retention characteristics (retention factor, resolution, peak symmetry, separation efficiency) were investigated. The systems consisting of acetonitrile and phosphate buffer of basic pH were found suitable for separation of vasopressin-related peptides.

• MeSH
• financování organizované MeSH
• oxidy chemie   MeSH
• peptidy analýza   MeSH
• vysokoúčinná kapalinová chromatografie přístrojové vybavení   MeSH
• zirkonium chemie   MeSH

Plectranthus (Lamiaceae), which-according to the latest systematic revision-includes three separate genera (Coleus, Plectranthus sensu stricto, and Equilabium), is a genus widely used in traditional medicine-mainly in the treatment of various ailments of the digestive tract, respiratory tract, and skin. Many species of Plectranthus s.l. have been shown to produce phenolic compounds and terpenes. Diterpenes, especially those of the abietane class, are the most studied group of secondary metabolites found in Plectranthus s.l., which is characterized by a significant structural diversity arising from the oxygenation and further rearrangement of the basic tricyclic abietane skeleton to a complete aromatization of the ring system. This review summarizes the known information on abietane diterpenes, showing their structures, sources, and biosynthesis. A classification of these compounds into nine groups, according to the arrangement of their ring C, is used. Royleanones, spirocoleons, and hydroquinones are the largest classes of abietane diterpenes, covering more than 70% of all the compounds reviewed.

• MeSH
• diterpeny abietanové chemie   MeSH
• diterpeny chemie   MeSH
• fytonutrienty chemie   izolace a purifikace   farmakologie   MeSH
• molekulární struktura MeSH
• Plectranthus chemie   MeSH
• rostlinné extrakty chemie   izolace a purifikace   farmakologie   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• přehledy MeSH

The non-dioxin-like environmental toxicant 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153), member of a group of persistent organic pollutants wide-spread throughout the environment, reduces gap junction intercellular communication (GJIC), an event possibly associated with tumor promotion. Since very few studies have investigated the signaling effectors and mode(s) of action of PCB153, and it is known that the gap junction (GJ) protein Cx43 can be regulated by the bioactive sphingolipid (SL) sphingosine 1-phosphate (S1P), this in vitro study mainly addresses whether SL metabolism is affected by PCB153 in rat liver epithelial WB-F344 cells. PCB153 treatment obtained significant changes in the S1P/ceramide (Cer) ratio, known to be crucial in determining cell fate. In particular, an increase in S1P at 30 min and a decrease of the bioactive lipid at 3 h were observed, whereas Cer level increased at 1 h and 24 h. Notably, a time-dependent modulation of sphingosine kinase (SphK), the enzyme responsible for S1P synthesis, and of its regulators, ERK1/2 and protein phosphatase PP2A, supports the involvement of these signaling effectors in PCB153 toxicity. Electrophysiological analyses, furthermore, indicated that the lipophilic environmental toxicant significantly reduced GJ biophysical properties, affecting both voltage-dependent (such as those formed by Cx43 and/or Cx32) and voltage-independent channels, thereby demonstrating that PCB153 may act differently on GJs formed by distinct Cx isoforms. SphK down-regulation alone induced GJIC impairment, and, when combined with PCB153, the acute effect on GJ suppression was additive. Moreover, after enzyme-specific gene silencing, the SphK1 isoform appears to be responsible for down-regulating Cx43 expression, while being the target of PCB153 at short-term exposure. In conclusion, we provide the first evidence of novel effectors in PCB153 toxic action in rat liver stem-like cells, leading us to consider SLs as potential markers for preventing GJIC deregulation and, thus, the tumorigenic action elicited by this environmental toxicant.

• MeSH
• dioxiny toxicita   MeSH
• elektrofyziologie metody   MeSH
• fosfotransferasy s alkoholovou skupinou jako akceptorem antagonisté a inhibitory   genetika   metabolismus   MeSH
• játra cytologie   účinky léků   MeSH
• konexin 43 metabolismus   MeSH
• krysa rodu rattus MeSH
• kultivované buňky MeSH
• lysofosfolipidy metabolismus   MeSH
• mezerový spoj účinky léků   fyziologie   MeSH
• mitogenem aktivovaná proteinkinasa 3 metabolismus   MeSH
• polychlorované bifenyly toxicita   MeSH
• proteinfosfatasa 2 genetika   metabolismus   MeSH
• sfingolipidy metabolismus   MeSH
• sfingosin analogy a deriváty   metabolismus   MeSH
• signální transdukce účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Komplexy kovov s biologickou aktivitou predstavujú perspektívnu a rýchle sa rozvíjajúcu oblasť farmakoterapie. Po prvej časti prehľadu o metalofarmakách venovanej antimikróbnym účinkom komplexov kovov a ich využitiu v diagnostike ochorení a druhej časti zaoberajúcej sa úlohou týchto zlúčenín v liečbe rakoviny sa táto tretia a záverečná časť prehľadu zameriava na vybrané ďalšie aplikácie kovov v terapii (predovšetkým na terapiu reumatoidnej artritídy, niektorých psychických ochorení, diabetu, ako aj na chelatačnú terapiu). Popri stručnom náčrte historického vývoja klinického využitia danej kategórie liečiv sú diskutované tiež ich chemické vlastnosti, toxicita, klinické aplikácie a mechanizmus účinku. Tento stručný prehľad má za cieľ poskytnúť základnú orientáciu v tejto problematike pre farmaceutov, chemikov a ostatných záujemcov o danú oblasť z radov odbornej verejnosti, ako aj motivovať k ďalšiemu štúdiu tejto atraktívnej oblasti farmaceutického výskumu.

Bioactive metal complexes represent a promising and rapidly evolving area of pharmacotherapy. After the first part of our survey on metallopharmaceuticals dealing with antimicrobial activity of metal complexes and their application in diagnostics and the second part dedicated to anticancer properties of these compounds, this third and last part of the review focuses on several other applications of metals in therapy (mainly on the therapy of rheumatoid arthritis, some mental diseases, diabetes, as well as on chelation therapy). Following a brief account of the historical development of clinical use of the respective category of drugs, their chemical properties, toxicity, clinical applications and mechanism of action are discussed. The aim of this brief survey is to provide basic outline of the area of metallopharmacy, aimed at specialists in pharmacy and chemistry as well as at the general educated public.

• Klíčová slova
• metalofarmaka,
• MeSH
• chelátová terapie metody   MeSH
• kovy * terapeutické užití   MeSH
• lidé MeSH
• lithium terapeutické užití   MeSH
• vanad terapeutické užití   MeSH
• zlato terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

Biodegradable polymer-based therapeutics have recently become essential drug delivery biomaterials for various bioactive compounds. Biodegradable and biocompatible polymer-based biomaterials fulfill the requirements of these therapeutics because they enable to obtain polymer biomaterials with optimized blood circulation, pharmacokinetics, biodegradability, and renal excretion. Herein, we describe an adaptable polymerization platform employed for the synthesis of long-circulating, stimulus-sensitive and biodegradable biomaterials, therapeutics, or theranostics. Four chain transfer agents (CTA) were designed and successfully synthesized for the reversible addition-fragmentation chain transfer polymerization, allowing the straightforward synthesis of hydrolytically biodegradable structures of block copolymers-based biomaterials. The controlled polymerization using the CTAs enables controlling the half-life of the hydrolytic degradation of polymer precursors in a wide range from 5 h to 21 days. Moreover, the antitumor drug pirarubicin (THP) was successfully conjugated to the polymer biomaterials via a pH-sensitive hydrazone bond for in vitro and in vivo experiments. Polymer conjugates demonstrated superior antitumor efficacy compared to basic linear polymer-based conjugates. Notably, the biodegradable systems, even though those with degradation in the order of hours were selected, increased the half-life of THP in the bloodstream almost two-fold. Indeed, the presented platform design enables the main chain-end specific attachment of targeting ligands or diagnostic molecules. The adaptable polymerization platform design allows tuning of the biodegradability rate, stimuli-sensitive drug bonding, and optimized pharmacokinetics to increase the therapy outcome and system targeting, thus allowing the preparation of targeted or theranostic polymer conjugates. STATEMENT OF SIGNIFICANCE: Biodegradable and biocompatible polymer-based biomaterials are recognized as potential future bioactive nanomedicines. To advance the development of such biomaterials, we developed polymerization platforms utilizing tailored chain transfer agents allowing the straightforward synthesis of hydrolytically degradable polymer biomaterials with tuned biodegradability from hours to several days. The platform allows for the synthesis of long-circulating, stimulus-sensitive and biodegradable biomaterial serving as drug carriers or theranostics. The therapeutic potential was validated by preparation of polymer biomaterials containing pirarubicin, anticancer drug, bound via pH sensitive bond and by showing prolonged blood circulation and increased antitumor activity while keeping the drug side effects low. This work paves the way for future development of biodegradable polymer biomaterials with advanced properties in drug delivery.

• MeSH
• biokompatibilní materiály farmakologie   chemie   MeSH
• doxorubicin * chemie   MeSH
• nosiče léků chemie   MeSH
• polymerizace MeSH
• polymery chemie   MeSH
• protinádorové látky * terapeutické užití   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Káva je jedným z najpopulárnejších a najčastejšie konzumovaných nápojov na svete vďaka svojim stimulačným účinkom na centrálny nervový systém, ale aj vďaka svojej chuti a aróme. Pražená káva je komplexná zmes viac ako 1 000 bioaktívnych zlúčenín. Kofeín a kyselina chlorogénová patria medzi základné a najznámejšie zložky v káve. Kofeín v jednej šálke kávy prejavuje svoj účinok prostredníctvom antagonizmu adenozínových receptorov, čiže sa naviaže na špecifické miesta v mozgových bunkách namiesto adenozínu, a tým oddiali nástup spánku. Nové epidemiologické štúdie a experimentálne výskumy naznačujú, že konzumácia kávy môže pomôcť predchádzať niekoľkým chronickým chorobám vrátane kardiovaskulárnych ochorení, diabetes mellitus 2. typu, degeneratívnych kognitívnych porúch a pravdepodobne má vplyv aj na výskyt nádorov hrubého čreva. Výsledky väčšiny prospektívnych kohortových štúdií o účinkoch kávy nepotvrdili fakt, že konzumácia kávy je spojená s významne zvýšeným rizikom kardiovaskulárnych ochorení. Existujú tiež dôkazy o tom, že káva bez kofeínu môže mať v niektorých ohľadoch podobné výhody ako bežná káva s obsahom kofeínu, čo naznačuje, že aj ďalšie zložky kávy prispievajú k ochrane nášho zdravia. U dospelých, ktorí konzumujú mierne množstvo kávy (3-4 šálky/deň poskytujúce 300-400 mg kofeínu denne), existuje málo dôkazov o zdravotných rizikách kávy.

Coffee is one of the most popular and most frequently consumed beverages in the world due to its stimulating effects on the central nervous system, but also due to its taste and aroma. Roasted coffee is a complex mixture of more than 1,000 bioactive compounds. Caffeine and chlorogenic acid are among the basic and most well-known components in coffee. Caffeine in one cup of coffee exerts its effect through antagonism of adenosine receptors, which binds to specific sites in brain cells instead of adenosine, thereby delaying the onset of sleep. New epidemiological studies and experimental research suggest that coffee consumption may help prevent several chronic diseases, including cardiovascular, diabetes mellitus type 2. degenerative cognitive disorders and colon cancer. The results of most prospective cohort studies on the effects of coffee have not confirmed the fact that coffee consumption is associated with a significantly increased risk of cardiovascular disease. There is also evidence that decaffeinated coffee may have similar benefits in some respects as regular coffee, suggesting that other coffee ingredients also help protect our health. In adults who consume moderate amounts of coffee (3-4 cups/day providing 300-400 mg/day of caffeine), there is little evidence of the health risks of coffee.

• MeSH
• diabetes mellitus 2. typu etiologie   MeSH
• káva * škodlivé účinky   MeSH
• kofein škodlivé účinky   MeSH
• lidé MeSH
• nádory etiologie   MeSH
• Parkinsonova nemoc etiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

In the present work, we developed a novel needleless emulsion electrospinning technique that improves the production rate of the core/shell production process. The nanofibres are based on poly-ε-caprolactone (PCL) as a continuous phase combined with a droplet phase based on Pluronic F-68 (PF-68). The PCL-PF-68 nanofibres show a time-regulated release of active molecules. Needleless emulsion electrospinning was used to encapsulate a diverse set of compounds to the core phase [i.e. 5-(4,6-dichlorotriazinyl) aminofluorescein -PF-68, horseradish peroxidase, Tetramethylrhodamine-dextran, insulin growth factor-I, transforming growth factor-β and basic fibroblast growth factor]. In addition, the PF-68 facilitates the preservation of the bioactivity of delivered proteins. The system's potential was highlighted by an improvement in the metabolic activity and proliferation of mesenchymal stem cells. The developed system has the potential to deliver susceptible molecules in tissue-engineering applications.

• MeSH
• biokompatibilní materiály farmakologie   MeSH
• dextrany chemie   MeSH
• emulze chemie   MeSH
• jehly MeSH
• kolagen typ II metabolismus   MeSH
• křenová peroxidasa metabolismus   MeSH
• mezenchymální kmenové buňky cytologie   účinky léků   metabolismus   MeSH
• mezibuněčné signální peptidy a proteiny farmakologie   MeSH
• miniaturní prasata MeSH
• nanovlákna chemie   ultrastruktura   MeSH
• poloxamer chemie   MeSH
• polyestery chemie   MeSH
• prasata MeSH
• proteiny aplikace a dávkování   MeSH
• rhodaminy chemie   MeSH
• tkáňové inženýrství metody   MeSH
• tkáňové podpůrné struktury chemie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• Klíčová slova
• elektroforéza kapilární,

• Konspekt
• Biochemie. Molekulární biologie. Biofyzika
• NLK Obory
• fyzika, biofyzika
• biomedicínské inženýrství

Dexrazoxane (DEX) is the only clinically used drug effective against anthracycline-induced cardiotoxicity and extravasation injury. However, the mechanism of its cardioprotective action still remains elusive. This paucity of comprehensive data is at least partially caused by the analytical difficulties associated with selective and sensitive simultaneous determination of the parent drug and its putative active metabolite ADR-925 in the relevant biological material. The aim of this study was to develop and validate the first LC-MS/MS method for simultaneous determination of DEX and ADR-925 in the isolated rat neonatal ventricular cardiomyocytes (NVCMs) and the cell culture medium. The analysis was performed on a Synergi Polar-RP column using the gradient profile of the mobile phase composed of 2mM ammonium formate and methanol. Electrospray ionization and ion trap mass analyzer were used as ionization and detection techniques, respectively. NVCMs were precipitated with methanol and the cell culture medium samples were diluted with the same solvent prior the LC-MS/MS analysis. The method was validated within the range of 4-80pmol/10(6) NVCMs and 7-70pmol/10(6) NVCMs for DEX and ADR-925, respectively, and at the concentrations of 8-100μM for both compounds in the culture cell medium. The practical applicability of this method was confirmed by the pilot analysis of NVCMs and the corresponding cell medium samples from relevant in vitro experiment. Hence, the LC-MS/MS method developed in this study represents a modern analytical tool suitable for investigation of DEX bioactivation inside the cardiomyocytes. In addition, the basic utility of the method for the analysis of DEX and ADR-925 in plasma samples was proved in a pilot experiment.

• MeSH
• chromatografie kapalinová metody   MeSH
• ethylendiaminy farmakokinetika   MeSH
• glycin analogy a deriváty   farmakokinetika   MeSH
• hmotnostní spektrometrie s elektrosprejovou ionizací metody   MeSH
• kardiomyocyty metabolismus   MeSH
• kardiovaskulární látky farmakokinetika   MeSH
• králíci MeSH
• krysa rodu rattus MeSH
• kultivované buňky MeSH
• novorozená zvířata MeSH
• pilotní projekty MeSH
• potkani Wistar MeSH
• razoxan farmakokinetika   MeSH
• senzitivita a specificita MeSH
• tandemová hmotnostní spektrometrie metody   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• validační studie MeSH