Chronic memantine administration prevents ouabain-induced hyperactivity in mice via maintenance of Na+, K+-ATPase activity in the hippocampus.

We have previously reported that mice received intracerebroventricular injection of ouabain, an inhibitor of Na+, K+-ATPase, exhibited hyperactivity via overactivation of glutamatergic neurons. Here we investigated the effects of memantine, a blocker of N-methyl-d-aspartate receptors, on ouabain-induced hyperactivity. In mice that received ouabain injection, chronic memantine administration prevented the hyperactivity and the decrease in the Na+, K+-ATPase activity in the hippocampus. Memantine also protected neurons without affecting glial activation in the hippocampus of these mice. Our results suggest that memantine improves hyperactivity via the maintenance of Na+, K+-ATPase activity and neurons in the hippocampus in this mouse model.

Open-shell character and second hyperpolarizabilities of one-dimensional chromium(II) chains: size dependence and bond-length alternation effect.

Using the long-range corrected spin-unrestricted density functional theory (LC-UBLYP) method, we have investigated the longitudinal third-order nonlinear optical (NLO) properties, i.e., the second hyperpolarizabilities γ of open-shell singlet one-dimensional (1D) extended metal atom chain (EMAC) systems, chromium(II) chains Cr(II)2n (n = 1-4), with different metal-metal bond lengths from the viewpoint of the open-shell character dependences of each d orbital contribution (dσ, dπ, dδ) to γ and of the chain-length dependence of γ. It turns out that the chain length dependences of the open-shell characters of dπ and dδ orbitals at any metal-metal bond length are negligible, while the dσ open-shell character decreases as a function of chain length. The systems display bell-shaped behaviors of γ as a function of the metal-metal bond length, in which the γ values attain maxima for intermediate dσ open-shell character. The maximum γ value (γmax) exhibits remarkable enhancement as a function of chain length. It is also found that the bond length alternation (BLA) significantly affects the γ values and their chain-length dependences. The present results provide the guiding principles for designing transition-metal complexes with open-shell singlet 1D metallic chains exhibiting large third-order optical nonlinearity.

Development and evaluation of a new intraoral voice assist device called the voice retriever.

Objective: Patients lose their voice after laryngectomy for laryngeal cancer or aspiration prevention surgery for severe dysphagia. To assist such patients, we developed and verified the utility of a novel vocalization method using a device termed the voice retriever (VR), in which the sound source is placed in the mouth. Methods: We investigated the effectiveness of the VR in patients. The VR consists of a mouthpiece with a built-in speaker and a dedicated application that serves as the sound source. We compared the speech intelligibility and naturalness in normal participants using VR and an electrolarynx (EL) for the first time as well as the voice-related quality of life (V-RQOL) in patients with dysphonia before and after using the VR. Results: The VR produced significantly higher 100-syllable test scores as well as fluency, amount of additional noise, intonation, intelligibility and overall long reading test ratings in the first-time VR and EL users. Furthermore, the VR use significantly improved the V-RQOL of participants with dysphonia. Conclusion: Compared to EL, VR allows more effective speech improvement in participants without experience using an alternative vocalization method and improves the V-RQOL in patients with dysphonia. Level of Evidence: Step 4.

Enhancement of the third-order nonlinear optical properties in open-shell singlet transition-metal dinuclear systems: effects of the group, of the period, and of the charge of the metal atom.

Metal-metal multiply bonded complexes in their singlet state have been predicted to form a novel class of "σ-dominant" third-order nonlinear optical compounds based on the results of dichromium(II) and dimolybdenum(II) systems (H. Fukui et al. J. Phys. Chem. Lett.2011, 2, 2063) whose second hyperpolarizabilities (γ) are enhanced by the contribution of the dσ electrons with an intermediate diradical character. In this study, using the spin-unrestricted coupled-cluster method with singles and doubles as well as with perturbative triples, we investigate the dependences of γ on the group and on the period of the transition metals as well as on their atomic charges in several open-shell singlet dimetallic systems. A significant enhancement of γ is observed in those dimetallic systems composed of (i) transition metals with a small group number, (ii) transition metals with a large periodic number, and (iii) transition metals with a small positive charge. From the decomposition of the γ values into the contributions of dσ, dπ, and dδ electrons, the γ enhancements are shown to originate from the dσ contribution, because it corresponds to the intermediate diradical character region. Furthermore, the amplitude of dσ contribution turns out to be related to the size of the d(z(2)) atomic orbital of the transition metal, which accounts for the dependence of γ on the group, on the period, and on the charge of the metal atoms. These dependences provide a guideline for an effective molecular design of highly efficient third-order nonlinear optical (NLO) systems based on the metal-metal bonded systems.

Thermal luminescence spectra of polyamides and their Maillard reaction with reducing sugars.

Thermal luminescence (TL) spectra of polyamides were measured with a Fourier-transform chemiluminescence spectrometer to elucidate the emission mechanism. A TL band of ε-polylysine with a peak at 542 nm observed at 403 K was assigned to the emission due to the interaction of the -CO-NH- group with oxygen molecules by comparison with nylon-6, polyglycine, and polyalanine. When the sample was kept at 453 K, the intensity of the TL band decreased and the wavelength of the peak shifted to 602 nm, which was assigned to the emission due to the interaction of the NH2 group on the side chain with oxygen molecules by comparison with monomeric lysine. A weak emission with a peak at 668 nm was assigned to the advanced glycosylation end products (AGEs) yielded by the Maillard reaction with a catalytic amount of water. To understand this reaction and to examine the TL emission of AGEs, we measured TL spectra of mixtures of polylysine and reducing sugars such as glucose, maltose, lactose, and dextrin. The minimum temperature for TL emission, wavelength of the peak and the relative intensities of the TL emission were found to depend on the size of the sugars.

Anti-neuroinflammatory activities of extract and polymethoxyflavonoids from immature fruit peels of Citrus 'Hebesu'.

Chronic neuroinflammation is reported to be associated in the progression of many neurodegenerative diseases and there is an increasing interest for the natural products as neuroprotective and anti-neuroinflammatory agents. In present research, we evaluated the potential inhibitory effects of extract, fractions, and isolated compounds from Citrus 'Hebesu' on lipopolysaccharide (LPS)-induced inflammatory responses using BV-2 murine microglial cells. The dried methanol extract (CH) was suspended in water and partitioned with hexane and ethyl acetate to give hexane soluble (CHH), ethyl acetate soluble (CHE), and water soluble (CHW) fractions. The extract (CH) and fractions CHH and CHE inhibited the expression of mRNA encoding pro-inflammatory cytokine interleukin (IL)-1ß. CHE and CHH were further purified by various column chromatographic methods to obtain hesperidin (1), tangeretin (2), 5-hydroxy-6,7,8,3',4'-pentamethoxyflavone (3), 3,5,6,7,8,3',4'-heptamethoxyflavone (4), nobiletin (5), 3,4,5-trimethoxy-trans-cinnamic alcohol (6), and meranzin hydrate (7). Among them, three polymethoxyflavonoids, 3, 4, and 5 significantly inhibited the expression of IL-1ß mRNA. PRACTICAL APPLICATIONS: Citrus 'Hebesu' is a local cultivar in Hyuga City, Miyazaki prefecture, Japan and its immature fruits are consumed with different food recipes. Till now, there is no detailed study on the chemical constituents and anti-neuroinflammatory activity of this cultivar. In this study, seven compounds were isolated from the peels of immature fruits. Methanol extract, hexane, and ethyl acetate fractions and three polymethoxyflavonoids showed a significant inhibitory activity against expression of IL-1ß mRNA. Consumption of peels of Citrus 'Hebesu' might play important role in the prevention and treatment of neurodegenerative diseases, however, detailed mechanism based in vivo studies are necessary in future for providing more scientific evidences.

Gas flux cyclic regime at an open vent magmatic column inferred from seismic and acoustic records.

On August 7, 2014, a new effusive vent opened on the northern flank of Stromboli. A characteristic pattern was observed in both seismic and infrasonic signal amplitudes prior to this effusive eruption. The pattern consisted of the repeating cycle: (1) quiet phase, (2) puffing phase, and (3) explosion phase. Correlation between seismic and infrasound signal suggests that pulses in the puffing phase were caused by repetitive bursts of small gas pockets at the central crater, while the explosion phase coincided with an explosion at the central crater. We show that degassing of the magma column occurred in cycles of increasing gas flux, which controlled the transition from a bubbly flow (puffing phase), to a slug flow (explosion phase) gas regime. The quiet phase was characterized by a constant time length of 150 s, indicating that the gas rose in the magma column as well-organized waves of gas layers. These cycles represent cyclic changes of the gas flux regime in the shallow magma column, associated with increases in the magma-gas supply input rate before the effusive eruption.

Na+, K+-ATPase inhibition causes hyperactivity and impulsivity in mice via dopamine D2 receptor-mediated mechanism.

Hyperactivity and impulsivity are common symptoms in several psychiatric disorders. Although dysfunction of Na+, K+-ATPase has been reported to be associated with the psychiatric disorders, it is not clear whether inhibition of Na+, K+-ATPase causes behavioral effects, including hyperactivity and impulsivity, in mice. Here, we evaluated the effect of intracerebroventricular (icv) injection of ouabain, an inhibitor of Na+, K+-ATPase, on hyperactivity and impulsivity in mice. At seven days after icv injection, ouabain-injected mice displayed the increase in the distance traveled in the open field arena in the open field test and the increase in the number of head-dipping behavior in the cliff avoidance test. Chlorpromazine or haloperidol, typical antipsychotics, reduced the hyperactivity and impulsivity in ouabain-injected mice. On the other hand, neither lithium carbonate nor valproate, established mood-stabilizing drugs, improved hyperactivity and impulsivity in our mouse model. Furthermore, ouabain-injected mice exhibited the increase in the number of c-fos-positive cells in the nucleus accumbens and the prefrontal cortex but not in the ventral tegmental area, which was reduced by haloperidol. These results suggest that the dysfunction of Na+, K+-ATPase causes hyperactivity and impulsivity via hyperactivation of dopamine D2 receptor-mediated signaling pathway, causing disturbed neuronal circuits in mice.