• Konspekt
• Farmacie. Farmakologie
• NLK Obory
• farmacie a farmakologie

Magnetic nanoparticles of ε-Fe1.76 Ga0.24 O3 with the volume-weighted mean size of 17 nm were prepared by thermal treatment of a mesoporous silica template impregnated with metal nitrates and were coated with silica shell of four different thicknesses in the range 6-24 nm. The bare particles exhibited higher magnetization than the undoped compound, 22.4 Am2 kg-1 at 300 K, and were characterized by blocked state with the coercivity of 1.2 T at 300 K, being thus the very opposite of superparamagnetic iron oxides. The relaxometric study of the silica-coated samples at 0.47 T revealed promising properties for MRI, specifically, transverse relaxivity of 89-168 s-1 mmol(f.u.)-1 L depending on the shell thickness was observed. We investigated the effects of the silica-coated nanoparticles on human A549 and MCF-7 cells. Cell viability, proliferation, cell cycle distribution, and the arrangement of actin cytoskeleton were assessed, as well as formation and maturation of focal adhesions. Our study revealed that high concentrations of silica-coated particles with larger shell thicknesses of 16-24 nm interfere with the actin cytoskeletal networks, inducing thus morphological changes. Consequently, the focal adhesion areas were significantly decreased, resulting in impaired cell adhesion.

• MeSH
• buněčný cyklus účinky léků   MeSH
• buňky A549 MeSH
• cytoskelet účinky léků   metabolismus   MeSH
• galium chemie   farmakologie   MeSH
• lidé MeSH
• magnetické nanočástice oxidů železa chemie   MeSH
• MFC-7 buňky MeSH
• oxid křemičitý chemie   farmakologie   MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Železo je důležitý biogenní stopový prvek (ve formě hemu je obsaženo v hemoglobinu, myoglobinu či cytochromech, některé sloučeniny obsahují železo vázané na atom síry, např. akonitáza, uplatňuje se i v imunitním systému). Patří mezi přechodné kovy, a proto se může ve formě Fe2+ účastnit tzv. Fentonovy reakce, při které dochází ke vzniku nebezpečného a pro organismus toxického hydroxylového radikálu. Metabolismus železa proto musí být velmi přísně regulován – oxidací Fe2+ na Fe3+ ceruloplasminem a jeho inaktivací vazbou na specifi cké proteiny (transferrin, ferritin nebo laktoferrin) nebo jeho chelatací. Přebytečné železo nemůže být z organismu vyloučeno, proto je regulován především jeho příjem. Regulace metabolismu železa probíhá jak na buněčné, tak na systémové úrovni. Na buněčné úrovni je zapojen systém Iron regulation proteins (IRPs)-Iron responsive elements (IREs), který řídí tvorbu proteinů, které se v metabolismu železa uplatňují, a to ovlivněním transkripce, změnou stability mRNA pro daný protein i změnou translace daného proteinu. Na systémové úrovni se v metabolismu železa uplatňuje nedávno objevený peptid hepcidin produkovaný především v hepatocytech, který má v organismu charakter hormonu. Cílovou molekulou hepcidinu je pravděpodobně ferroportin – exportér železa z buňky. Výsledkem působení hepcidinu je snížený export železa z enterocytů duodena a z makrofágů a tedy i snížený přísun železa transferrinem erytroblastům. Tím dojde ke snížení erytropoezy a k anémii. Syntéza hepcidinu je regulována na úrovni transkripce (ovlivnění promotoru genu pro hepcidin a tedy tvorby mRNA). Jeho sekreci tlumí snížená zásoba železa, anémie a hypoxie, stimuluje ji nadbytek železa a především zánět (prostřednictvím IL-6). Zvýšená hladina hepcidinu při zánětu je tak důležitým faktorem pro vznik anémie chronických chorob.

Iron is an important biogenic trace element (in the heme-form is contained in the hemoglobin, myoglobin or cytochromes, some compounds contain iron bound to sulphur atom (aconitase), iron also plays an important role in the immune system). Iron belongs to transition elements and thereby it can be involved in its ferrous form in Fenton reaction, which generates dangerous and toxic hydroxyl radical. Hence metabolism of iron must be strictly regulated – by ceruloplasmin oxidation of Fe2+ on Fe3+ and by inactivation of Fe2+ by its bond to specifi c proteins (transferrin, ferritin or lactoferrin) or its chelation. Iron excess cannot be eliminated thereby especially its uptake is regulated. Iron metabolism is regulated both on cellular and systemic level. System Iron regulation proteins (IRPs) – Iron responsive elements (IREs) participates on cellular level. It controls the production of proteins involved in iron metabolism by interference of transcription, change in mRNA stability and change in translation. Recently discovered peptide hepcidin produced especially in hepatocytes participates on systemic level. The target molecule for hepcidin is probably ferroportin – iron cell exporter. The impact of hepcidin is the decrease of iron uptake from duodenal enterocytes and macrophages and thereby the decrease of iron distribution in transferrin-form to erythroblasts. The result of hepcidin action is the decrease of erythropoiesis and anemia. The hepcidin synthesis is regulated on transcription level (hepcidin gene promotor and production of mRNA is infl uenced). Hepcidin synthesis is decreased by low iron store, anemia and hypoxia, increased by high iron stores and especially in the state of infl ammation (through IL-6). The higher level of hepcidin during infl ammatory state is one of the important factors in anemia of chronic disease genesis.

• MeSH
• anemie z nedostatku železa imunologie   metabolismus   MeSH
• biologický transport MeSH
• erytrocyty metabolismus   MeSH
• financování organizované MeSH
• hepatocyty metabolismus   MeSH
• kationické antimikrobiální peptidy krev   MeSH
• kostní dřeň metabolismus   MeSH
• lidé MeSH
• receptory transferinu MeSH
• transferin metabolismus   MeSH
• železo metabolismus   MeSH
• Check Tag
• lidé MeSH

Byla purifikována a charakterizována protease stabilni v organických rozpoštědlech. Její molekulová hmotnost byla stanovena pomocí SDS-PAGE a SEC na 26 kDa. Purifikovaná proteasa měla nejvyšší aktivitu při 70°C a její pH optimum bylo velmi široké (5,0 – 12.0). Po ošetření 5 mM EDTA a β-mercaptoethanolem zůstával enzym aktivní. Proteasa měla po hodinové inkubaci při 30°C v přítomnosti 20, 40 a 60 % (v/v) organických rozpouštědel, jako jsou například DMSO, DMF, aceton, ethanol, iso-propanol a toluen vyšší aktivitu a stabilitu. Proteolytická aktivita byla v přítomnosti Mn2+ iontů prokazatelně vyšší a v přítomnosti 5, 10 a 15 mM Pb2+, Zn2+, K+, Fe2+, Co2+, Cd2+, Mg2+, Ca2+, Fe3+ iontů po dobu 1h při 30°C si zachovávala více než 90 % aktivity.

In the present research, stable in organic solvent protease from a new thermophilic actinomycete isolate, was purified and characterized. The approximate molecular mass of 26 kDa was determined by SDS-PAGE and SEC. The purified protease showed maximum activity at 70°C and exhibited broad pH optimum (5.0 – 12.0). After treatment with 5 mM EDTA and β-mercaptoethanol the enzyme remained fully active. The protease showed an increased activity and stability in the presence of 20, 40 and 60 % (v/v) organic solvents such as DMSO, DMF, acetone, ethanol, iso-propanol and toluene when incubated for 1h at 30°C. The proteolytic activity was significantly enhanced in presence of Mn2+ and remained more than 90 % active in the presence of 5, 10 and 15 mM Pb2+, Zn2+, K+, Fe2+, Co2+, Cd2+, Mg2+, Ca2+, Fe3+ ions for 1h at 30°C. The kinetic constants were also determined.

• MeSH
• Actinobacteria * enzymologie   izolace a purifikace   růst a vývoj   MeSH
• kultivační média MeSH
• proteasy * fyziologie   izolace a purifikace   MeSH
• proteolýza MeSH
• rozpouštědla * aplikace a dávkování   MeSH
• teplota MeSH
• Publikační typ
• práce podpořená grantem MeSH

Coprecipitation of FeCl2 and FeCl3 with aqueous ammonia was used to prepare iron oxide nanoparticles dispersible in aqueous medium. Oxidation of the particles with sodium hypochlorite then yielded maghemite (γ-Fe2 O3 ) nanoparticles which were coated with two types of coating -d-mannose or poly(l-lysine) (PLL) as confirmed by FTIR analysis. The particles were <10 nm according to transmission electron microscopy. Their hydrodynamic particle size was ∼180 nm (by dynamic light scattering). The d-mannose-, PLL-coated, and neat γ-Fe2 O3 particles as well as commercial Resovist® were used to label rat macrophages. The viability and contrast properties of labeled macrophages were compared. PLL-coated γ-Fe2 O3 nanoparticles were found optimal. The labeled macrophages were injected to rats monitored in vivo by magnetic resonance imaging up to 48 h. Transport of macrophages labeled with PLL-γ-Fe2 O3 nanoparticles in rats was confirmed. Tracking of macrophages using the developed particles can be used for monitoring of inflammations and cell migration in cell therapy.

• MeSH
• buněčný tracking metody   MeSH
• kontrastní látky * chemie   farmakologie   MeSH
• krysa rodu rattus MeSH
• magnetická rezonanční tomografie metody   MeSH
• makrofágy radiografie   MeSH
• nanočástice chemie   MeSH
• polylysin * chemie   farmakologie   MeSH
• velikost částic MeSH
• železité sloučeniny * chemie   farmakologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Článek hodnotí dlouhodobé změny červeného krevního obrazu u elitní běžkyně. V průběhu 5 let bylo odebráno 29 krevních vzorků z kubitální žíly, u nichž byly hodnoceny a sledovány jednotlivé parametry červeného krevního obrazu. Všechny vzorky byly zpracovány ve specializované hematologické laboratoři. Všechny parametry byly statisticky zpracovány. Probandka měla diagnostikovanou sideropenickou anémii a byla pod pravidelnou suplementací železa vy výši 100 mg Fe2+ denně po celou dobu sledování. Kromě hodnoty sérové železa žádná z komponent nepřekročila referenční meze. Setrvalý mírný vzestup jsme zjistili u sérového železa, feritinu, střední koncentrace hemoglobinu v erytrocytu a naopak mírný pokles u celkového počtu erytrocytů, středního objemu erytrocytu a hematokritu. Na rozdíl od literatury jsme nezjistili typickou běžeckou makrocytózu, kterou popisuje Eichner (2001), ani nepotvrdili jednoznačnou korelaci mezi hladinou sérového železa a feritinem, které uvádí Falon (2004). Sérové Fe a Hb sezónně kolísaly, s maximem v zimním přípravném období a poklesem v závěru závodního období, respektive předzávodním období u hemoglobinu.

Case study elite female endurance runner is focused on changes in red blood count in long-term training load. In the course of five years, 29 blood samples were taken from the cubical vein in which individual components of the red blood cell were monitored. All samples were processing in a specialized haematology laboratory. All blood components were statistically analysed. Proband has diagnostic sideropenic anaemia and iron was supplemented with approximately 100 mg of Fe2+ per day throughout the monitoring period. In addition to serum iron, none of the components moved beyond the reference values. A slight upward trend was observed in serum iron, ferritin, haemoglobin and mean haemoglobin concentration in the erythrocyte in the observed period, a slight decrease in erythrocyte count, mean red blood cell count and haematocrit. We have not confirmed elite runners running macrocytosis, which reports Eichner (2001), even higher levels of ferritin in the female runners (Fallon, 2004). Seasonal analysis showed a higher seasonality for serum iron, lower for haemoglobin. The highest value is achieved in the prepare-winter period, when does an aerobic workout.

• MeSH
• dospělí MeSH
• ferritiny krev   MeSH
• hematologické testy metody   MeSH
• krevní obraz MeSH
• lidé MeSH
• maratonský běh * MeSH
• sideroblastická anemie farmakoterapie   MeSH
• tělesná námaha fyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH

The use of knowledge from technetium radiochemistry (even from nuclear medicine applications) allows us to select an sorbent for 99mTc radionuclide sorption, which is hydroxyapatite. Using radioisotope indication, the 99mTcO4- sorption process on synthetic hydroxyapatite was studied by the batch method in the presence of SnCl2 and FeSO4 reducing agents. The complexing organic ligands' effect on the 99mTcO4- sorption under reducing conditions was investigated. In the presence of Sn2+ ions without the addition of organic ligand, the sorption percentage reached above 90% independently of the environment. In the presence of Fe2+ ions without the addition of organic ligand, the sorption of 99mTcO4- was significantly lower and was at approximately 6%, depending on the concentration of Fe2+ ions in solution. The effect of complexing organic ligands on the 99mTcO4- sorption on hydroxyapatite from the aqueous solution, acetate buffer and phosphate buffer decreases in the following order for Sn2+: oxalic acid > ethylenediaminetetraacetic acid > ascorbic acid. In the presence of Fe2+ ions without organic ligands, the sorption reached up to 15% depending on the composition of the solution. The addition of oxalic acid and ascorbic acid increased the sorption up to 80%. The ethylenediaminetetraacetic acid had no significant effect on the sorption of technetium on hydroxyapatite.

• MeSH
• 99mTc-technecistan sodný * MeSH
• adsorpce MeSH
• EDTA MeSH
• hydroxyapatit chemie   MeSH
• indikátory a reagencie MeSH
• kyselina oxalová MeSH
• ligandy MeSH
• technecium * analýza   MeSH
• voda MeSH
• Publikační typ
• časopisecké články MeSH

The duration of in-situ generation of iron corrosion products (FeCPs) prior the remediation process (so called "aging" of metallic iron (Fe0)), was found as the key parameter affecting the efficiency of Fe0 for water remediation. Batch experiments were performed in buffered solutions (pH 4.0, 4.7 and 5.5) and under oxic conditions (presence of dissolved oxygen) using Zn2+ as probe contaminant. The time-dependent (0-16 d) concentration changes of aqueous Fe2+ and Zn2+ were monitored using differential pulse polarography (DPP). During the time of pre-corrosion varying from 0 to 6 d, an "induction period" of the corrosion occurs in the first one - 2 h when no Fe2+ ion is released in the solution. After this period, Fe2+ was identified in solution and its concentration progressively increases up to 6 h, then starts to decrease and after 6 d nearly disappears. Experiments with Zn2+ reveal that the most efficient Fe0 remediation occurs after 6 h of pre-corrosion. This coherence thus proves that the presence, the amount and the age of FeCPs ("degree" of corrosion) significantly impact the removal efficiency of Zn2+ in Fe0/H2O systems. The present study severely refute the wording 'reactivity loss' and states that progress in designing sustainable Fe0/H2O systems will not be achieved before the role of "active" FeCPs is clarified.

• MeSH
• chemické látky znečišťující vodu analýza   chemie   MeSH
• elektrochemie metody   MeSH
• koroze MeSH
• železnaté sloučeniny chemie   MeSH
• Publikační typ
• časopisecké články MeSH

With the aim to develop a new anticancer agent, we prepared poly[N-(2-hydroxypropyl)methacrylamide-co-methyl 2-methacrylamidoacetate] [P(HP-MMAA)], which was reacted with hydrazine to poly[N-(2-hydroxypropyl)methacrylamide-co-N-(2-hydrazinyl-2-oxoethyl)methacrylamide] [P(HP-MAH)] to conjugate doxorubicin (Dox) via hydrazone bond. The resulting P(HP-MAH)-Dox conjugate was used as a coating of magnetic γ-Fe2 O3 nanoparticles obtained by the coprecipitation method. In vitro toxicity of various concentrations of Dox, P(HP-MAH)-Dox, and γ-Fe2 O3 @P(HP-MAH)-Dox nanoparticles was determined on somatic healthy cells (human bone marrow stromal cells hMSC), human glioblastoma line (GaMG), and primary human glioblastoma (GBM) cells isolated from GBM patients both at a short and prolonged exposition time (up to 7 days). Due to hydrolysis of the hydrazone bond in acid milieu of tumor cells and Dox release, the γ-Fe2 O3 @P(HP-MAH)-Dox nanoparticles significantly decreased the GaMG and GBM cell growth compared to free Dox and P(HP-MAH)-Dox in low concentration (10 nM), whereas in hMSCs it remained without effect. γ-F2 O3 @PHP nanoparticles alone did not affect the viability of any of the tested cells.

• MeSH
• akrylamidy chemie   MeSH
• doxorubicin chemie   metabolismus   farmakologie   MeSH
• glioblastom patologie   MeSH
• lidé MeSH
• magnetické nanočástice chemie   MeSH
• nádorové buněčné linie MeSH
• nosiče léků chemie   MeSH
• polymery chemie   MeSH
• proliferace buněk MeSH
• protinádorové látky chemie   metabolismus   farmakologie   MeSH
• regulace genové exprese u nádorů účinky léků   MeSH
• uvolňování léčiv MeSH
• viabilita buněk účinky léků   MeSH
• železité sloučeniny chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Maghemite (γ-Fe2O3) nanoparticles were obtained by coprecipitation of ferrous and ferric salts in an alkaline medium followed by oxidation; the nanoparticles were coated with poly(N,N-dimethylacrylamide) (PDMA) and characterized by transmission electron microscopy, attenuated total reflection (ATR) Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering, thermogravimetric and elemental analyses, and magnetic measurements in terms of particle morphology, size, polydispersity, amount of coating, and magnetization, respectively. The effects of α-tocopherol (Toc) and its phenolic (Toc-6-OH) and acetate (Toc-6-Ac) derivatives on Fe2+ release from γ-Fe2O3@PDMA, as well as from γ-Fe2O3 and CuFe2O4 nanoparticles (controls), were examined in vitro using 1,10-phenanthroline. The presence of tocopherols enhanced spontaneous Fe2+ release from nanoparticles, with Toc-6-OH exhibiting more activity than neat Toc. All of the nanoparticles tested were found to initiate blood lipid oxidation in a concentration-dependent manner, as determined by analysis of 2-thiobarbituric acid reactive species. Wistar rats with Walker-256 carcinosarcoma (a model of mammary gland carcinosarcoma) received Toc-6-Ac, magnetic nanoparticles, or their combination per os, and the antitumor activity of each treatment was determined in vivo. γ-Fe2O3@PDMA nanoparticles exhibited increased antitumor activity compared to both commercial CuFe2O4 particles and the antitumor drug doxorubicin. Moreover, increased antitumor activity was observed after combined administration of γ-Fe2O3@PDMA nanoparticles and Toc-6-Ac; however, levels of bilirubin, aspartate aminotransferase, and white bloods normalized and did not differ from those of the intact controls. The antitumor activity of the γ-Fe2O3 nanoparticles strongly correlated with Fe2+ release from the nanoparticles but not with nanoparticle-initiated lipid peroxidation in vitro.

• MeSH
• akrylamidy chemie   MeSH
• alfa-tokoferol aplikace a dávkování   chemie   MeSH
• experimentální nádory mléčných žláz farmakoterapie   MeSH
• karcinosarkom farmakoterapie   MeSH
• lékové transportní systémy metody   MeSH
• magnetické nanočástice aplikace a dávkování   chemie   MeSH
• potkani Wistar MeSH
• spektroskopie infračervená s Fourierovou transformací MeSH
• transmisní elektronová mikroskopie MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• železité sloučeniny chemie   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH