Cytarabine (Ara-C) is a synthetic isomer of cytidine that differs from cytidine and deoxycytidine only in the sugar. The use of arabinose instead of deoxyribose hinders the formation of phosphodiester linkages between pentoses, preventing the DNA chain from elongation and interrupting the DNA synthesis. The minor structural alteration (the inversion of hydroxyl at the 2' positions of the sugar) leads to change of the biological activity from anti-depressant and DNA/RNA block builder to powerful anti-cancer.
View Article and Find Full Text PDFObjectives: Assessment of myocardial strain by feature tracking magnetic resonance imaging (FT-MRI) in human fetuses with and without congenital heart disease (CHD) using cardiac Doppler ultrasound (DUS) gating.
Methods: A total of 43 human fetuses (gestational age 28-41 weeks) underwent dynamic cardiac MRI at 3 T. Cine balanced steady-state free-precession imaging was performed using fetal cardiac DUS gating.
Favipiravir (6-fluoro-3-hydroxypyrazine-2-carboxamide, FPV), an active pharmaceutical component of the drug discovered and registered in March 2014 in Japan under the name Avigan, with an indication for pandemic influenza, has been studied. The study of this compound was prompted by the idea that effective processes of recognition and binding of FPV to the nucleic acid are affected predominantly by the propensity to form intra- and intermolecular interactions. Three nuclear quadrupole resonance experimental techniques, namely H-N cross-relaxation, multiple frequency sweeps, and two-frequency irradiation, followed by solid-state computational modelling (density functional theory supplemented by the quantum theory of atoms in molecules, 3D Hirshfeld Surfaces, and reduced density gradient) approaches were applied.
View Article and Find Full Text PDFObjective: To describe clinical characteristics associated with immunotherapy in patients with new-onset refractory status epilepticus (NORSE) and assess its timing and effect on outcomes at hospital discharge after six and 12 months of follow-up. Our secondary aim was to apply the cryptogenic NORSE (C-NORSE) score to subjects in order to evaluate its utility in identifying C-NORSE in our cohort.
Methods: This was a retrospective single university hospital cohort study (2004-2021) of adults and children with NORSE.
The impact of repetitive magnetic stimulation (rTMS) on cortex varies with stimulation parameters, so it would be useful to develop a biomarker to rapidly judge effects on cortical activity, including regions other than motor cortex. This study evaluated rTMS-evoked EEG potentials (TEP) after 1 Hz of motor cortex stimulation. New features are controls for baseline amplitude and comparison to control groups of sham stimulation.
View Article and Find Full Text PDFObjective: Vinpocetine has been shown to enhance memory in animal models, with possible cognitive benefit in humans. The present study sought to demonstrate if vinpocetine can enhance cognition in healthy volunteers or patients with epilepsy. In addition, we compare blood levels of vinpocetine and its active metabolite (apovincaminic acid; AVA) in humans and animals to further characterize factors related to possible therapeutic benefit.
View Article and Find Full Text PDFSystems with short hydrogen bonds (H-bonds) are notoriously difficult to describe even using cutting edge experimental techniques supported by advanced computational protocols. One of the most challenging issues is the highly dislocated H-bonded proton, which is typically smeared over a large area, featuring complex dynamics governed by pronounced nuclear quantum effects. Thus, in combination with experimental results, these systems offer a rich platform for the benchmarking of various computational approaches and methods.
View Article and Find Full Text PDFA nonenzymatic dynamic kinetic resolution of acyclic and cyclic benzylic alcohols is reported. The approach merges rapid transition-metal-catalyzed alcohol racemization and enantioselective Cu-H-catalyzed dehydrogenative Si-O coupling of alcohols and hydrosilanes. The catalytic processes are orthogonal, and the racemization catalyst does not promote any background reactions such as the racemization of the silyl ether and its unselective formation.
View Article and Find Full Text PDFBackground And Objectives: Most people agree that cognitive capabilities are an integral component of wisdom and its development. However, a question that has received less attention is whether people view maintaining cognitive capabilities as a necessary prerequisite for maintaining wisdom.
Research Design And Methods: This study used a mixed-methods approach to evaluate people's views about the relationship between age-related cognitive declines, Alzheimer's disease (AD), and wisdom.
Four polymorphic forms of carbamazepine have been simultaneously investigated by H NMR and N NQR. The results show that the proton spin-lattice relaxation time and the N NQR spectra can be used to differentiate between various polymorphic forms. Spontaneous transformations from Form II to Form III and from Form IV to Form III have been investigated through their influence on the N NQR spectrum and the proton NMR signal and spin-lattice relaxation.
View Article and Find Full Text PDFA modification of Slusher-Hahn's double resonance technique is described and experimentally tested. It is based on application of multiple frequency sweeps and can be used for a rapid location of nuclear quadrupole resonance (NQR) frequencies. The resolution of the present technique is relatively low but, when the NQR frequencies are located, it is easy to use either the Slusher-Hahn's technique or pulse NQR to determine the NQR frequencies with a higher precision.
View Article and Find Full Text PDFPeople with epilepsy are at increased risk for neuropsychological dysfunction due to multiple factors, of which the most amendable are antiseizure medications (ASMs). Antiseizure medication effectiveness is frequently determined by tolerability. In this study, we compared the neuropsychological effects of eslicarbazepine acetate (ESL) and carbamazepine immediate-release (CBZ) using a randomized, double-blind, crossover design in healthy volunteers with a 2-week titration and 4-week maintenance phase in each treatment arm (CBZ = 400 mg BID and ESL = 800 mg qAM).
View Article and Find Full Text PDFThe non-enzymatic kinetic resolution of racemic mixtures of alcohols by silylation had been unknown before the turn of the century. This stands in stark contrast to established acylation techniques. The same applies to the related desymmetrization of diols.
View Article and Find Full Text PDFIn terms of drug disposal and metabolism SDR21C1 (carbonyl reductase 1; CBR1) exerts an assorted substrate spectrum among a large variety of clinically relevant substances. Additionally, this short-chain dehydrogenase/reductase is extensively expressed in most tissues of the human body, thus underpinning its role in xenobiotic metabolism. Reduction of the chemotherapeutic daunorubicin (DAUN) to daunorubicinol (DAUNol) is a prominent example of its metabolic properties in terms of chemoresistance and cardiotoxicity.
View Article and Find Full Text PDFJ Nucl Med Technol
June 2019
Nuclear medicine technologists (NMTs) have multiple opportunities to advance their careers beyond an entry-level NMT. Many careers that NMTs can obtain require additional skills, education, or qualifications. Participating in professional development (PD) opportunities is necessary to acquire the skills necessary for career advancement.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
February 2019
A broad range of tertiary propargylic alcohols were kinetically resolved by catalyst-controlled enantioselective silylation. This non-enzymatic kinetic resolution is catalyzed by a Cu-H species and makes use of the commercially available precatalyst MesCu/(R,R)-Ph-BPE and a simple hydrosilane as the resolving reagent. Both alkyl,aryl- as well as dialkyl-substituted propargylic alcohols participate, and especially high selectivity factors are achieved when the alkyne terminus carries a TIPS group, which also enables facile post-functionalization in this position (s up to 207).
View Article and Find Full Text PDFPhys Chem Chem Phys
December 2018
The position of protons in hydrogen bonds is often uncertain to some degree, as the technique most often used for structure determination, X-ray diffraction, is sensitive to electron density, which is not particularly abundant around protons. In hydrogen bonds, protons introduce an additional problem: the potential for proton motion is inherently anharmonic and thus requires the consideration of nuclear quantum effects (NQEs). Here, we demonstrate that 14N NQR spectroscopy is able to rather accurately determine proton positions in N-HN bonds, in certain cases with an accuracy comparable to that of X-ray and neutron diffraction at room temperature.
View Article and Find Full Text PDFHop-derived compounds have been subjected to numerous biomedical studies investigating their impact on a wide range of pathologies. Isomerised bitter acids (isoadhumulone, isocohumulone and isohumulone) from hops, used in the brewing process of beer, are known to inhibit members of the aldo-keto-reductase superfamily. Aldo-keto-reductase 1B10 (AKR1B10) is upregulated in various types of cancer and has been reported to promote carcinogenesis.
View Article and Find Full Text PDFJ Gerontol B Psychol Sci Soc Sci
April 2019
Objectives: As people get older, they show a relative preference to remember positive information over negative information. In two experiments, we tested whether the positivity of older adults' memory is affected by stereotype threat about age-related cognitive declines. We also tested whether highlighting a positive aging stereotype (older adults are wise) would inoculate older adults from stereotype threat's adverse effects.
View Article and Find Full Text PDFXanthohumol (XN), a prenylated chalcone unique to hops (Humulus lupulus) and two derived prenylflavanones, isoxanthohumol (IX) and 8-prenylnaringenin (8-PN) gained increasing attention as potential anti-diabetic and cancer preventive compounds. Two enzymes of the aldo-keto reductase (AKR) superfamily are notable pharmacological targets in cancer therapy (AKR1B10) and in the treatment of diabetic complications (AKR1B1). Our results show that XN, IX and 8-PN are potent uncompetitive, tight-binding inhibitors of human aldose reductase AKR1B1 (K = 15.
View Article and Find Full Text PDFSolid State Nucl Magn Reson
September 2016
Here we describe a method for the extraction of (14)N quadrupole parameters from a (1)H-(14)N cross-relaxation spectrum by fitting the lineshapes of the (14)N quadrupole transitions. The procedures used typically to fit quadrupole lineshapes are not directly applicable to fit the (1)H-(14)N cross-relaxation spectrum, because the presence of proton homonuclear dipolar interaction broadens the lineshapes considerably and prevents a reliable determination of Cq and η from a single lineshape. Instead, one must fit two or even three lineshapes originating from the same nitrogen site simultaneously.
View Article and Find Full Text PDFThe polymorphism of anhydrous caffeine (1,3,7-trimethylxanthine; 1,3,7-trimethyl-1H-purine-2,6-(3H,7H)-dione) has been studied by (1)H-(14)N NMR-NQR (Nuclear Magnetic Resonance-Nuclear Quadrupole Resonance) double resonance and pure (14)N NQR (Nuclear Quadrupole Resonance) followed by computational modelling (Density Functional Theory, supplemented Quantum Theory of Atoms in Molecules with Reduced Density Gradient) in solid state. For two stable (phase II, form β) and metastable (phase I, form α) polymorphs the complete NQR spectra consisting of 12 lines were recorded. The assignment of signals detected in experiment to particular nitrogen sites was verified with the help of DFT.
View Article and Find Full Text PDFThe clinical application of anthracyclines, like daunorubicin and doxorubicin, is limited by two factors: dose-related cardiotoxicity and drug resistance. Both have been linked to reductive metabolism of the parent drug to their metabolites daunorubicinol and doxorubicinol, respectively. These metabolites show significantly less anti-neoplastic properties as their parent drugs and accumulate in cardiac tissue leading to chronic cardiotoxicity.
View Article and Find Full Text PDFThree experimental techniques (1)H-(14)N NQDR, (13)C CP/MAS NMR and X-ray and Density Functional Theory (GGA/BLYP with PBC) and Hirshfeld surfaces were applied for the structure-activity oriented studies of two phyto-antioxidants and anticarcinogens: indole-3-carbinol, I3C, and 3,3'-diindolylmethane, DIM, (its bioactive metabolite). One set of (14)N NQR frequencies for DIM (2.310, 2.
View Article and Find Full Text PDF