• Klíčová slova
• karboxymaltóza železa,
• MeSH
• anemie z nedostatku železa * farmakoterapie   MeSH
• chronická renální insuficience komplikace   MeSH
• hypofosfatemie etiologie   MeSH
• idiopatické střevní záněty komplikace   MeSH
• intravenózní podání * metody   MeSH
• lidé MeSH
• osteomalacie etiologie   MeSH
• pooperační komplikace farmakoterapie   MeSH
• poporodní období krev   účinky léků   MeSH
• silné menstruační krvácení farmakoterapie   MeSH
• srdeční selhání farmakoterapie   komplikace   MeSH
• železnaté sloučeniny * aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• Check Tag
• lidé MeSH

DNA three-way junctions (3WJ) represent one of the simplest supramolecular DNA structures arising as intermediates in homologous recombination in the absence of replication. They are also formed transiently during DNA replication. Here we examine the ability of Fe(II)-based metallohelices to act as DNA 3WJ binders and induce DNA damage in cells. We investigated the interaction of eight pairs of enantiomerically pure Fe(II) metallohelices with four different DNA junctions using biophysical and molecular biology methods. The results show that the metallohelices stabilize all types of tested DNA junctions, with the highest selectivity for the Y-shaped 3WJ and minimal selectivity for the 4WJ. The potential of the best stabilizer of DNA junctions and, at the same time, the most selective 3WJ binder investigated in this work to induce DNA damage was determined in human colon cancer HCT116 cells. These metallohelices proved to be efficient in killing cancer cells and triggering DNA damage that could yield therapeutic benefits.

• MeSH
• DNA * chemie   MeSH
• konformace nukleové kyseliny MeSH
• lidé MeSH
• nádory * genetika   MeSH
• poškození DNA MeSH
• železnaté sloučeniny MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Non-psychotropic cannabinoids (e.g., cannabidiol, cannabinol and cannabigerol) are contained in numerous alimentary and medicinal products. Therefore, predicting and studying their possible side effects, such as changes in DNA methylation, is an important task for assessing the safety of these products. Interference with TET enzymes by chelating ferrous ions can contribute to the altered methylation pattern. All tested cannabinoids displayed a strong affinity for Fe(II) ions. Cannabidiol and cannabinol exhibited potent inhibitory activities (IC50 = 4.8 and 6.27 μM, respectively) towards the TET1 protein, whereas cannabigerol had no effect on the enzyme activity. An in silico molecular docking study revealed marked binding potential within the catalytic cavity for CBD/CBN, but some affinity was also found for CBG, thus the total lack of activity remains unexplained. These results imply that cannabinoids could affect the activity of the TET1 protein not only due to their affinity for Fe(II) but also due to other types of interactions (e.g., hydrophobic interactions and hydrogen bonding).

• MeSH
• Cannabis * chemie   MeSH
• kanabidiol * chemie   farmakologie   MeSH
• kanabinoidy * farmakologie   MeSH
• kanabinol farmakologie   MeSH
• simulace molekulového dockingu MeSH
• železnaté sloučeniny MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The design of efficient and safe gene delivery vehicles remains a major challenge for the application of gene therapy. Of the many reported gene delivery systems, metal complexes with high affinity for nucleic acids are emerging as an attractive option. We have discovered that certain metallohelices-optically pure, self-assembling triple-stranded arrays of fully encapsulated Fe-act as nonviral DNA delivery vectors capable of mediating efficient gene transfection. They induce formation of globular DNA particles which protect the DNA from degradation by various restriction endonucleases, are of suitable size and electrostatic potential for efficient membrane transport and are successfully processed by cells. The activity is highly structure-dependent-compact and shorter metallohelix enantiomers are far less efficient than less compact and longer enantiomers.

• MeSH
• buněčné linie MeSH
• DNA chemie   ultrastruktura   MeSH
• exprese genu MeSH
• fluorescenční protilátková technika MeSH
• genetické vektory * chemie   ultrastruktura   MeSH
• kationty chemie   MeSH
• kovové nanočástice chemie   ultrastruktura   MeSH
• lidé MeSH
• mikroskopie atomárních sil metody   MeSH
• molekulární struktura MeSH
• průtoková cytometrie MeSH
• reportérové geny MeSH
• technika přenosu genů * MeSH
• transfekce MeSH
• viabilita buněk MeSH
• železnaté sloučeniny chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Chemotherapy plays an essential role in the management of cancer worldwide. However, it is a non-specific treatment limited by major drawbacks, thus identification and testing of new promising molecular structures representing potential drug candidates are urgently needed. In this work, ferrocene complexes as potential antitumor drugs that display cytotoxicity in low micromolar concentrations against ovarian cancer cells A2780 and SK-OV-3 were investigated to identify their mode of action. Their mechanism of cellular accumulation was studied using differential pulse voltammetry and inductively coupled plasma - mass spectrometry. Their mode of cell death induction was determined by changes in the mitochondrial membrane potential, production of reactive oxygen species and by Annexin V staining. Transferrin receptors were identified as key mediators of intracellular accumulation of ferrocenes and the extent of cellular uptake reflected the anticancer activity of individual compounds. Functional analysis revealed activation of intrinsic apoptosis as a dominant mechanism leading to regulated cell death induced in ovarian cancer cells by ferrocenes. Ferrocenes represent a group of promising sandwich organometallic complexes exerting cytotoxic activity. We suggest their application not only as standalone chemotherapeutics but also as modifying substituents of known drugs to improve their antitumor effects.

• MeSH
• antitumorózní látky farmakologie   terapeutické užití   MeSH
• apoptóza účinky léků   MeSH
• léky antitumorózní - screeningové testy MeSH
• lidé MeSH
• membránový potenciál mitochondrií účinky léků   MeSH
• metaloceny farmakologie   terapeutické užití   MeSH
• nádorové buněčné linie MeSH
• nádory vaječníků farmakoterapie   patologie   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• receptory transferinu metabolismus   MeSH
• železnaté sloučeniny farmakologie   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: Nanomaterials consist of particles smaller than 100 nm - nanoparticles (NPs). Their nano dimensions allow them to penetrate through various membranes and enter into the bloodstream and disseminate into different body organs. Massive expansion of nanotechnologies together with production of new nanoparticles which have not yet been in contact with living organisms may pose a potential health problem. It is therefore necessary to investigate the health impact of NPs after experimental exposure. Comparison of the effect of TiO2 and NPs Fe3O4 in Wistar rats at time intervals 1, 7, 14 and 28 days was performed by studying the cytotoxic effect in the isolated inflammatory cells from bronchoalveolar lavage (BAL). METHODS: Wistar rats were intravenously (i.v.) given a suspension of NPs TiO2 or Fe3O4 (coated by sodium oleate) via the tail vein. After time intervals of 1, 7, 14 and 28 days, we sacrificed the animals under anaesthesia, performed BAL and isolated the cells. The number of animals in the individual groups was 7-8. We examined the differential count of BAL cells (alveolar macrophages - AM, polymorphonuclear leukocytes - PMN, lymphocytes - Ly); viability and phagocytic activity of AM; the proportion of immature and polynuclear cells and enzymes - cathepsin D - CAT D, lactate dehydrogenase - LDH and acid phosphatase - ACP. RESULTS: We found that TiO2 NPs are relatively inert - without induction of inflammatory and cytotoxic response. Exposure to nanoparticles Fe3O4 induced - under the same experimental conditions - in comparison with the control and TiO2 a more extensive inflammatory and cytotoxic response, albeit only at 1, 7 and 14 days after injection. CONCLUSIONS: The results suggest that TiO2 and Fe3O4 nanoparticles used in our study were transferred from the bloodstream to the respiratory tract, but this effect was not observed at 28 days after i.v. injection, probably due to their removal from the respiratory tract.

• MeSH
• intravenózní podání MeSH
• kovové nanočástice aplikace a dávkování   toxicita   MeSH
• krysa rodu rattus MeSH
• nemoci dýchací soustavy chemicky indukované   MeSH
• oxid železnato-železitý aplikace a dávkování   toxicita   MeSH
• potkani Wistar MeSH
• titan aplikace a dávkování   toxicita   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Sideropenie a sideropenní anémie postihují nejméně polovinu pacientů trpících Crohnovou nemocí a ulcerózní kolitidou. Adekvátní substituce perorálním železem je součástí všeobecně akceptovaných doporučení u těchto nemocných. Nesnášenlivost a výskyt nežádoucích účinků při substituci perorálními preparáty obsahujícími anorganické železo je u nemocných s idiopatickými střevními záněty (IBD – inflammatory bowel disease) relativně častá. Metodika a výsledky: Soubor 43 pacientů s IBD ve fázi remise, trpících sideropenií (feritin < 30 µg/l) nebo lehkou sideropenní anémií (Hb 100–120, resp. 130 g/l). Pacienti užívali GlobiFer®forte s obsahem hemového i minerálního železa po dobu 12 týdnů. Medián koncentrace hemoglobinu se signifikantně zvýšil v porovnání s výchozí hodnotou 123,5 g/l v týdnu 0 na 133,5 g/l v týdnu 12 (p = 0,004) a medián středního objemu erytrocytu se zvýšil z 85,2 fL v týdnu 0 na 87,3 fL v týdnu 12 (p = 0,05). Výskyt mírných nežádoucích účinků byl zaznamenán pouze u jediného pacienta. Závěr: Hemové železo v preparátu GlobiFer®forte je velmi dobře snášeno IBD pacienty a vede k úpravě sideropenie nebo lehké sideropenní anémie.

Introduction: Sideropenia and sideropenic anemia occurring in more than a half of patients suffering from inflammatory bowel disease (IBD). The efficacy in replenishing of the iron storage or therapy of sideropenic anemia is part of the national guidelines for IBD population. Unfortunately, in IBD patients, therapy with inorganic iron preparations is associated with intolerance or side effects which occurred relatively often. Methods and results: A cohort of 43 IBD patients without inflammatory activity (31 with Crohn's disease and 12 with ulcerative colitis) with sideropenia (ferritin level < 30 µg /L) or mild sideropenic anemia (hemoglobin 100 g/L - 120 g/L) were recruited for 12 weeks therapy with GlobiFer® forte tablet containing heme iron and also inorganic iron. The median hemoglobin concentration significantly increased from week 0 to week 12 (123.5 g/L to 133.5 g/L) (P = 0.004) and median mean red cell corpuscular volume changed from 85.2 fL at week 0 to 87.3 fL at week 12 (P = 0.05). GlobiFer®forte was very well tolerated and side effects occurred only in one patient. Conclusion: The heme iron which is part of GlobiFer®forte was very well tolerated and this therapy led to the normalization of hemoglobin concentration and mean red cell volume at the end of the therapy.

• MeSH
• hypochromní anemie * farmakoterapie   MeSH
• idiopatické střevní záněty * komplikace   MeSH
• lidé MeSH
• pilotní projekty MeSH
• potravní doplňky MeSH
• železnaté sloučeniny aplikace a dávkování   metabolismus   terapeutické užití   MeSH
• Check Tag
• lidé MeSH

• Klíčová slova
• Globifer forte,
• MeSH
• anemie z nedostatku železa farmakoterapie   MeSH
• dietní železo aplikace a dávkování   metabolismus   MeSH
• hypochromní anemie farmakoterapie   MeSH
• idiopatické střevní záněty * komplikace   metabolismus   MeSH
• lidé MeSH
• vztahy mezi strukturou a aktivitou MeSH
• železnaté sloučeniny terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• novinové články MeSH

Two novel coordination compounds containing heterocyclic bidentate N,N-donor ligand 2-(furan-2-yl)-5-(pyridin-2-yl)-1,3,4-oxadiazole (fpo) were synthesized. A general formula for compounds originating from perchlorates of iron, cobalt, and fpo can be written as: [M(fpo)2(H2O)2](ClO4)2 (M = Fe(II) for (1) Co(II) for (2)). The characterization of compounds was performed by general physico-chemical methods-elemental analysis (EA), Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR) in case of organics, and single crystal X-ray diffraction (sXRD). Moreover, magneto-chemical properties were studied employing measurements in static field (DC) for 1 and X-band EPR (Electron paramagnetic resonance), direct current (DC), and alternating current (AC) magnetic measurements in case of 2. The analysis of DC magnetic properties revealed a high spin arrangement in 1, significant rhombicity for both complexes, and large magnetic anisotropy in 2 (D = -21.2 cm-1). Moreover, 2 showed field-induced slow relaxation of the magnetization (Ueff = 65.3 K). EPR spectroscopy and ab initio calculations (CASSCF/NEVPT2) confirmed the presence of easy axis anisotropy and the importance of the second coordination sphere.

• MeSH
• anizotropie MeSH
• elektronová paramagnetická rezonance MeSH
• furany chemie   MeSH
• kobalt chemie   MeSH
• komplexní sloučeniny chemie   MeSH
• krystalografie rentgenová MeSH
• magnetická rezonanční spektroskopie MeSH
• molekulární modely MeSH
• oxadiazoly chemie   MeSH
• spektroskopie infračervená s Fourierovou transformací MeSH
• spektroskopie Mossbauerova MeSH
• železnaté sloučeniny chemie   MeSH
• železo chemie   MeSH
• Publikační typ
• časopisecké články MeSH

Settled road dust was examined to detect the presence of non-airborne submicron and nano-sized iron-based particles and to characterize these particles. Samples were collected from a road surface near a busy road junction in the city of Ostrava, Czech Republic, once a month from March to October. The eight collected samples were subjected to a combination of experimental techniques including elemental analysis, Raman microspectroscopy, scanning electron microscopy (SEM) analysis, and magnetometry. The data thereby obtained confirmed the presence of non-agglomerated spherical nano-sized iron-based particles, with average sizes ranging from 2 down to 490 nm. There are several sources in road traffic which generate road dust particles, including exhaust and non-exhaust processes. Some of them (e.g., brake wear) produce iron as the dominant metallic element. Raman microspectroscopy revealed forms of iron (mainly as oxides, Fe2O3, and mixtures of Fe2O3 and Fe3O4). Moreover, Fe3O4 was also detected in samples of human tissues from the upper and lower respiratory tract. In view of the fact that no agglomeration of those particles was found by SEM, it is supposed that these particles may be easily resuspended and represent a risk to human health due to inhalation exposure, as proved by the detection of particles with similar morphology and phase composition in human tissues.

• MeSH
• dýchací soustava účinky léků   metabolismus   MeSH
• inhalační expozice analýza   MeSH
• lidé MeSH
• monitorování životního prostředí metody   MeSH
• oxid železnato-železitý analýza   MeSH
• prach analýza   MeSH
• velikost částic MeSH
• velkoměsta MeSH
• výfukové emise vozidel analýza   MeSH
• železité sloučeniny analýza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• velkoměsta MeSH