University Karlova

Prague, Czech Republic

University Karlova

Prague, Czech Republic
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Elischer A.,Narodni Ustav Dusevniho Zdravi v Klecanech | Jurickova L.,Univerzita Palackeho | Bartos A.,Narodni Ustav Dusevniho Zdravi v Klecanech | Bartos A.,University Karlova
Prakticky Lekar | Year: 2017

This article presents a case study of a cognitively impaired geriatric patient, which has been diagnosed with Alzheimer's disease with a high degree of certainty. However, for 2.5-years following the diagnosis, a proper treatment plan had not been observed. Our aim is to show a case where the patient is treated by medication that isn't indicated for the given diagnosis (piracetam in this case). Additionally, we show certain questionable courses of treatment that physicians may encounter in practice. Our overall goal is to highlight the importance of early detection of cognitive impairment and starting an effective course of treatment for early-stage Alzheimer's disease immediately. Advanced dementia causing impaired ability to perform tasks of daily living, which develops in late-stage Alzheimer's disease, is a life-threatening condition in geriatric patients responding poorly to targeted medication and placing a great strain on caregivers.


Chilla S.N.M.,University of Mons | Zemek O.,University Karlova | Kotek J.,University Karlova | Boutry S.,University of Mons | And 12 more authors.
Bioorganic and Medicinal Chemistry | Year: 2017

A new facile synthetic strategy was developed to prepare bifunctional monophosphinic acid Ln-DOTA derivatives, Gd-DO2AGAPNBn and Gd- DO2AGAPABn. The relaxivities of the Gd-complexes are enhanced compared to Gd-DOTA. Monophosphinic acid arm of these Gd-complexes affords enhancement of inner sphere water exchange rate due to its steric bulkiness. The different functionalities of DO2AGAPNBn were appended in trans positions and are designed to conjugate identical or different vectors according to the potential applications. The conjugation of Gd-DO2AGAPABn with E3 peptide known to target apoptosis was successfully performed and in vivo MRI allowed cell death detection in a mouse model. © 2017 Elsevier Ltd


Nemethova A.,Ustav organicke Technology | Syslova K.,Ustav organicke Technology | Pelclova D.,University Karlova | Kacer P.,Ustav organicke Technology
Chemicke Listy | Year: 2012

The work deals with preparation and characterization of polymer immunoparticles used as a separation tool for biomarkers from biological fluids like urine, plasma etc. Polymer imunoparticles consist of antibodies immobilized in a polyvinyl alcohol and polyethylene glycol matrix. Prepared immunoparticles, containing monoclonal antibodies against 8-iso Prostaglandin F 2α, were used as a tool for a preliminary separation of 8-iso Prostaglandin F 2α (a marker of oxidative stress) from complex biological matrix (urine) before a highly specific and precise detection and quantification by LC-ESI-MS method. The developed method was characterized by high precision and accuracy. Functionality of the method was tested in a clinical study where urine concentration levels of 8-iso Prostaglandin F 2α in patients with diagnosis of asbestosis or silicosis (oxidative stress induced diseases) and control group were compared.


Lima L.M.P.,New University of Lisbon | Delgado R.,New University of Lisbon | Hermann P.,University Karlova | Sevcik R.,Masaryk University | And 6 more authors.
European Journal of Inorganic Chemistry | Year: 2012

The lanthanide (Ln 3+) complexes of three cyclen-based ligands containing three methylphosphonate pendant arms were studied, the ligands being 1,4,7,10-tetraazacyclododecane-1,4,7-triyltris(methylphosphonic acid) (H 6do3p), 3-[4,7,10-tris(phosphonomethyl)-1,4,7,10-tetraazacyclododec- 1-yl]propanoic acid (H 7do3p1pr), and 10-(3-hydroxypropyl)-1,4,7,10- tetraazacyclododecane-1,4,7-triyltris(methylphosphonic acid) (H 6do3p1ol). The three macrocyclic ligands form complexes of very high thermodynamic stability with all studied Ln 3+ ions. Kinetic studies showed that the acid-assisted dissociation of Ce 3+ complexes of these ligands is much faster than for the complex of the related ligand H 8dotp [1,4,7,10-tetraazacyclododecane-1,4,7,10- tetrayltetrakis(methylphosphonic acid)]. The number of water molecules coordinated to the Eu 3+ and Gd 3+ complexes was estimated to be < 1 for the do3p1ol ligand but ca. 1 for the other two ligands, as obtained by time-resolved luminescence spectroscopy and by 1H and 17O relaxometric measurements. The NMR spectroscopic data indicate the existence of a considerable contribution from second-sphere water molecules to the relaxivity of all the Gd 3+ complexes studied. The 1H and 31P NMR spectra of the Eu 3+, Yb 3+ and Lu 3+ complexes showed that the propionate arm in the [Ln(do3p1pr)] 4- complexes and the propanol arm in the [Ln(do3p1ol)] 3- complexes are not bound to the Ln 3+ ion. The [Ln(do3p)] 3- and [Ln(do3p1pr)] 4- complexes have a clear preference for the TSAP (twisted square antiprismatic) isomer, while both SAP (square antiprismatic) and TSAP isomers are present in solutions of the [Ln(do3p1ol)] 3- complexes. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Kerdjoudj R.,CNRS Laboratory of Subatomic Physics and Associated Technologies | Pniok M.,University Karlova | Alliot C.,ARRONAX GIP | Alliot C.,University of Nantes | And 5 more authors.
Dalton Transactions | Year: 2016

The complexation ability of DOTA analogs bearing one methylenephosphonic (DO3AP) or methylenephosphinic (DO3APPrA and DO3APABn) acid pendant arm toward scandium was evaluated. Stability constants of their scandium(iii) complexes were determined by potentiometry combined with 45Sc NMR spectroscopy. The stability constants of the monophosphinate analogues are somewhat lower than that of the Sc-DOTA complex. The phosphorus acid moiety interacts with trivalent scandium even in very acidic solutions forming out-of-cage complexes; the strong affinity of the phosphonate group to Sc(iii) precludes stability constant determination of the Sc-DO3AP complex. These results were compared with those obtained by the free-ion selective radiotracer extraction (FISRE) method which is suitable for trace concentrations. FISRE underestimated the stability constants but their relative order was preserved. Nonetheless, as this method is experimentally simple, it is suitable for a quick relative comparison of stability constant values under trace concentrations. Radiolabelling of the ligands with 44Sc was performed using the radioisotope from two sources, a 44Ti/44Sc generator and 44mSc/44Sc from a cyclotron. The best radiolabelling conditions for the ligands were pH = 4, 70 °C and 20 min which were, however, not superior to those of the parent DOTA. Nonetheless, in vitro behaviour of the Sc(iii) complexes in the presence of hydroxyapatite and rat serum showed sufficient stability of 44Sc complexes of these ligands for in vivo applications. PET images and ex vivo biodistribution of the 44Sc-DO3AP complex performed on healthy Wistar male rats showed no specific bone uptake and rapid clearance through urine. © The Royal Society of Chemistry 2016.


Drahos B.,University Karlova | Drahos B.,CNRS Center for Molecular Biophysics | Pniok M.,University Karlova | Havlickova J.,University Karlova | And 5 more authors.
Dalton Transactions | Year: 2011

A new class of macrocyclic ligands based on 1-oxa-4,7-diazacyclononane was synthesized and their Mn2+ complexes were investigated with respect to stability and relaxation properties. Each ligand has two pendant arms involving carboxylic (H2L1 - 1-oxa-4,7-diazacyclononane-4, 7-diacetic acid), phosphonic (H4L2 - 1-oxa-4,7- diazacyclononane-4,7-bis(methylenephosphonic acid)), phosphinic (H 2L3 - 1-oxa-4,7-diazacyclononane-4,7- bis(methylenephosphinic acid)) or phenylphosphinic (H2L4 - 1-oxa-4,7-diazacyclononane-4,7-bis[methylene(phenyl)phosphinic acid]) acid moieties. H2L3 and H2L4 were synthesized for the first time. The crystal structure of the Mn2+ complex with H2L4 confirmed a coordination number of 6 for Mn2+. The protonation constants of all ligands and the stability constants of their complexes with Mn2+ and some biologically or biomedically relevant metal ions were determined by potentiometry. The protonation sequence of H2L3 was followed by 1H and 31P NMR titration and the second protonation step was attributed to the second macrocyclic nitrogen atom. The potentiometric data revealed a relatively low thermodynamic stability of the Mn2+ complexes with all ligands investigated. For H2L3 and H2L 4, full Mn2+ complexation cannot be achieved even with 100% ligand excess. The transmetallation of MnL1 and MnL2 with Zn2+ was too fast to be followed at pH 6. Variable temperature 1H NMRD and 17O NMR measurements have been performed on MnL1 and MnL2 to provide information on water exchange and rotational dynamics. The 17O chemical shifts indicate hydration equilibrium between mono- and bishydrated species for MnL1, while MnL2 is monohydrated. The water exchange is considerably faster on MnL1 (kex 298 = 1.2 × 109 s-1) than on MnL2 (kex 298 = 1.2 × 107 s-1). Small endogenous anions (phosphate, carbonate, citrate) do not replace the coordinated water in either of the complexes, but they induce their slow decomposition. All Mn2+ complexes are stable toward air-oxidation. © The Royal Society of Chemistry 2011.

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