Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development

Mood stabilising drugs such as lithium (LiCl) and valproic acid (VPA) are the first line agents for treating conditions such as Bipolar disorder and Epilepsy. However, these drugs have potential developmental effects that are not fully understood. This study explores the use of a simple human neurosphere-based in vitro model to characterise the pharmacological and toxicological effects of LiCl and VPA using gene expression changes linked to phenotypic alterations in cells. Treatment with VPA and LiCl resulted in the differential expression of 331 and 164 genes respectively. In the subset of VPA targeted genes, 114 were downregulated whilst 217 genes were upregulated. In the subset of LiCl targeted genes, 73 were downregulated and 91 were upregulated. Gene ontology (GO) term enrichment analysis was used to highlight the most relevant GO terms associated with a given gene list following toxin exposure. In addition, in order to phenotypically anchor the gene expression data, changes in the heterogeneity of cell subtype populations and cell cycle phase were monitored using flow cytometry. Whilst LiCl exposure did not significantly alter the proportion of cells expressing markers for stem cells/undifferentiated cells (Oct4, SSEA4), neurons (Neurofilament M), astrocytes (GFAP) or cell cycle phase, the drug caused a 1.4-fold increase in total cell number. In contrast, exposure to VPA resulted in significant upregulation of Oct4, SSEA, Neurofilament M and GFAP with significant decreases in both G2/M phase cells and cell number. This neurosphere model might provide the basis of a human-based cellular approach for the regulatory exploration of developmental impact of potential toxic chemicals.

QT interval prolongation related to psychoactive drug treatment:a comparison of monotherapy versus polytherapy

Background - Several antipsychotic agents are known to prolong the QT interval in a dose dependent manner. Corrected QT interval (QTc) exceeding a threshold value of 450 ms may be associated with an increased risk of life threatening arrhythmias. Antipsychotic agents are often given in combination with other psychotropic drugs, such as antidepressants, that may also contribute to QT prolongation. This observational study compares the effects observed on QT interval between antipsychotic monotherapy and psychoactive polytherapy, which included an additional antidepressant or lithium treatment. Method - We examined two groups of hospitalized women with Schizophrenia, Bipolar Disorder and Schizoaffective Disorder in a naturalistic setting. Group 1 was composed of nineteen hospitalized women treated with antipsychotic monotherapy (either haloperidol, olanzapine, risperidone or clozapine) and Group 2 was composed of nineteen hospitalized women treated with an antipsychotic (either haloperidol, olanzapine, risperidone or quetiapine) with an additional antidepressant (citalopram, escitalopram, sertraline, paroxetine, fluvoxamine, mirtazapine, venlafaxine or clomipramine) or lithium. An Electrocardiogram (ECG) was carried out before the beginning of the treatment for both groups and at a second time after four days of therapy at full dosage, when blood was also drawn for determination of serum levels of the antipsychotic. Statistical analysis included repeated measures ANOVA, Fisher Exact Test and Indipendent T Test. Results - Mean QTc intervals significantly increased in Group 2 (24 ± 21 ms) however this was not the case in Group 1 (-1 ± 30 ms) (Repeated measures ANOVA p < 0,01). Furthermore we found a significant difference in the number of patients who exceeded the threshold of borderline QTc interval value (450 ms) between the two groups, with seven patients in Group 2 (38%) compared to one patient in Group 1 (7%) (Fisher Exact Text, p < 0,05). Conclusions - No significant prolongation of the QT interval was found following monotherapy with an antipsychotic agent, while combination of these drugs with antidepressants caused a significant QT prolongation. Careful monitoring of the QT interval is suggested in patients taking a combined treatment of antipsychotic and antidepressant agents.

A multidisciplinary lithium clinic:the pharmacist's role

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Waveguide fabrication in lithium-niobo-phosphate glasses by high repetition rate femtosecond laser:route to non-equilibrium material’s states

We study waveguide fabrication in lithium-niobo-phosphate glass, aiming at a practical method of single-stage fabrication of nonlinear integrated-optics devices. We observed chemical transformations or material redistribution during the course of high repetition rate femtosecond laser inscription. We believe that the laser-induced ultrafast heating and cooling followed by elements diffusion on a microscopic scale opens the way toward the engineering non-equilibrium sates of matter and thus can further enhance Refractive Index (RI) contrasts by virtue of changing glass composition in and around the fs tracks. © 2014 Optical Society of America.

1.2-μm semiconductor disk laser frequency doubled with periodically poled lithium tantalate crystal

In this letter, we demonstrate an optically pumped semiconductor disk laser frequency doubled with a periodically poled lithium tantalate crystal. Crystals with various lengths were tested for intracavity frequency conversion. The semiconductor disk laser exploited GaInNAs-based active region with GaAsAlAs distributed Bragg mirror to produce emission at 1.2- μm wavelength. The frequency doubled power up to 760 mW at the wavelength of 610 nm was achieved with a 2-mm-long crystal. © 2010 IEEE.

Periodically poled lithium tantalate crystals for efficient SHG generation

In this paper, we investigate SHG efficiency dependency on crystal length. Four periodically-poled MgSLT crystals (PPMgSLT) of 2, 4, 11 and 25 mm in length were used, for intracavity frequency doubling of an optically-pumped GalnNAs semiconductor disk laser.

Intracavity generation of 610nm light by periodically poled near-stoichiometric lithium tantalate

Intracavity frequency doubling of an optically pumped GaInNAs semiconductor disk laser by a periodically poled near-stoichiometric lithium tantalate crystal has been investigated. Stable second-harmonic generation at 610nm has been achieved with an output power of 730mW, limited only by the spectral acceptance range and Fresnel losses of the crystal. Spectral tuning of 8nm was realised with a Fabry-Pérot etalon. © The Institution of Engineering and Technology.

Design and fabrication of micro-structured waveguides in lithium niobate

We review our recent work on the numerical design and optimisation of buried, micro-structured waveguides (WGs) that can be formed in a lithium niobate (LiNbO3) crystal by the method of direct femtosecond laser inscription. We also report on the possibility of fabricating such WGs using a high-repetition-rate, chirped-pulse oscillator system. Refractive index contrasts as high as -0.0127 have been achieved for individual modification tracks. The results pave the way for developing micro-structured WGs with low-loss operation across a wide spectral range, extending into the mid-infrared region up to the end of the transparency range of the host material. © 2014 IEEE.

Control of the properties of micro-structured waveguides in lithium niobate crystal

We study numerically depressed-cladding, buried waveguides that can be formed in a lithium niobate crystal by femtosecond laser writing. We demonstrate that the guiding properties can be controlled by the waveguide structural characteristics.

Optimisation of micro-structured waveguides in lithium niobate (z-cut)

We present an optimization procedure to improve the propagation properties of the depressed cladding, buried micro-structured waveguides formed in a z-cut lithium niobate (LN) crystal by high repetition rate femtosecond (fs) laser writing. It is shown that the propagation wavelength for which the confinement losses of ordinary (O) and extraordinary ordinary (E) polarizations are below 1 dB/cm can be optimized beyond 3 micro meter for hexagonal WG structures with seven rings of tracks.

Optimization of micro-structured waveguides in lithium niobate

We describe how the guiding properties of buried, micro-structured waveguides that can be formed in a lithium niobate crystal by direct femtosecond laser writing can be optimized for low-loss operation in the mid-infrared region beyond 3 μm.

Improved lithium storage properties of electrospun TiO2 with tunable morphology:from porous anatase to necklace rutile

Three-dimensional TiO2 with tunable morphology and crystalline phase was successfully prepared by the electrospinning technique and subsequent annealing. Porous-shaped anatase TiO2, cluster-shaped anatase TiO2, hierarchical-shaped rutile (minor) TiO2 and nano-necklace rutile (major) TiO2 were achieved at 500, 600, 700 and 800°C, respectively. The mechanism of the formation of these tailored morphologies and crystallinity was investigated. Lithium insertion properties were evaluated by galvanostatic and potentiostatic modes in half-cell configurations. By combining the large surface area, open mesoporosity and stable crystalline phase, the porous-shaped anatase TiO2 exhibited the highest capacity, best rate and cycling performance among the four samples. The present results demonstrated the usefulness of three-dimensional TiO 2 as an anode for lithium storage with improved electrode performance. © 2013 The Royal Society of Chemistry.