In memory of Yurii Vasil'evich Kopaev Alferov, Zhores I; Andreev, Aleksandr F; Aseev, Aleksandr L ...
Physics Uspekhi,
05/2013, Letnik:
56, Številka:
5
Journal Article
In memory of Gelii Frolovich Zharkov Andreev, Aleksandr F; Bolotovskiĭ, Boris M; Vasil'ev, Mikhail A ...
Physics Uspekhi,
11/2004, Letnik:
47, Številka:
11
Journal Article
Schizophrenia is a chronic, complex and heterogeneous mental disorder, with pathological features of disrupted neuronal excitability and plasticity within limbic structures of the brain. These ...pathological features manifest behaviorally as positive symptoms (including hallucinations, delusions and thought disorder), negative symptoms (such as social withdrawal, apathy and emotional blunting) and other psychopathological symptoms (such as psychomotor retardation, lack of insight, poor attention and impulse control). Altered glutamate neurotransmission has for decades been linked to schizophrenia, but all commonly prescribed antipsychotics act on dopamine receptors. LY404039 is a selective agonist for metabotropic glutamate 2/3 (mGlu2/3) receptors and has shown antipsychotic potential in animal studies. With data from rodents, we provide new evidence that mGlu2/3 receptor agonists work by a distinct mechanism different from that of olanzapine. To clinically test this mechanism, an oral prodrug of LY404039 (LY2140023) was evaluated in schizophrenic patients with olanzapine as an active control in a randomized, three-armed, double-blind, placebo-controlled study. Treatment with LY2140023, like treatment with olanzapine, was safe and well-tolerated; treated patients showed statistically significant improvements in both positive and negative symptoms of schizophrenia compared to placebo (P < 0.001 at week 4). Notably, patients treated with LY2140023 did not differ from placebo-treated patients with respect to prolactin elevation, extrapyramidal symptoms or weight gain. These data suggest that mGlu2/3 receptor agonists have antipsychotic properties and may provide a new alternative for the treatment of schizophrenia.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Purinergic P2X7 receptors (P2X7) have now been proven to play an important role and represent an important therapeutic target in many pathological conditions including neurodegeneration. Here, we ...investigated the impact of peptides on purinergic signaling in Neuro-2a cells through the P2X7 subtype in in vitro models. We have found that a number of recombinant peptides, analogs of sea anemone Kunitz-type peptides, are able to influence the action of high concentrations of ATP and thereby reduce the toxic effects of ATP. The influx of calcium, as well as the fluorescent dye YO-PRO-1, was significantly suppressed by the studied peptides. Immunofluorescence experiments confirmed that the peptides reduce the P2X7 expression level in neuronal Neuro-2a cells. Two selected active peptides, HCRG1 and HCGS1.10, were found to specifically interact with the extracellular domain of P2X7 and formed stable complexes with the receptor in surface plasmon resonance experiments. The molecular docking approach allowed us to establish the putative binding sites of the most active HCRG1 peptide on the extracellular domain of the P2X7 homotrimer and propose a mechanism for regulating its function. Thus, our work demonstrates the ability of the Kunitz-type peptides to prevent neuronal death by affecting signaling through the P2X7 receptor.
The crystal structure of the first-synthesized compound EuErCuS3 was determined from X-ray powder diffraction data: orthorhombic crystal system, space group Pnma, structural type Eu2CuS3: ...a = 10.1005(2) Å, b = 3.91255(4)Å, c = 12.8480(2) Å; V = 507.737(14) Å3, Z = 4, and ρx = 6.266 g/cm3. The temperatures and enthalpies of reversible polymorphic transitions and incongruent melting of the compound were determined by DSC: Tα↔β = 1524 K, ΔНα↔β = 2.3 ± 0.2 kJ∙mol−1; Tβ↔γ = 1575 K, ΔНβ↔γ = 0.7 ± 0.1 kJ∙mol−1; Tγ↔δ = 1602 K; ΔНγ↔δ = 1.3 ± 0.1 kJ∙mol−1 and Tcr = 1735 ± 10 K, ΔНcr = −3.5 ± 0.3 kJ∙mol−1. IR spectra were recorded in the range from 50 to 400 cm−1. The compound was found to be IR-transparent in the range 4000–400 cm−1. The compound was characterized by Raman spectroscopy. The observed spectra featured both Raman lines and luminescence. Ab initio calculations of the EuErCuS3 crystal structure and phonon spectrum were performed, the frequencies and types of fundamental modes were determined, and the involvement of constituent ions in the IR and Raman modes was assessed from an analysis of the ab initio displacement vectors. The vibrational spectra were interpreted. EuErCuS3 manifests a ferrimagnetic transition at 4.8 K. Its microhardness is 2850 MPa. The obtained data can serve as the basis for predicting the properties of EuLnCuS3 compounds. Valence states for Eu (2+) and Er (3+) are proved both by the XRD and optical methods. Optical band gap was found to be 1.934 eV from diffuse reflectance spectrum.
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•The EuLnCuS3 compound exhibit ferrimagnetic properties at low temperature.•The polymorphic transitions for EuLnCuS3 are identified at high temperature.•EuErCuS3 is a wide-gap semiconductor.•Valence purity of Eu2+ is proved via both XRD and optical techniques•The ab initio calculation of the Raman and infrared spectra of EuErCuS3, made for Pnma symmetry, agrees well with experiment.