The novel antipsychotic cariprazine stabilizes gamma oscillations in rat hippocampal slices

Background and purpose: Gamma oscillations are fast rhythmic fluctuations of neuronal network activity ranging from 30 to 90 Hz that establish a precise temporal background for cognitive processes such as perception, sensory processing, learning, and memory. Alterations of gamma oscillations have been observed in schizophrenia and are suggested to play crucial roles in the generation of positive, negative, and cognitive symptoms of the disease. Experimental approach: In this study, we investigated the effects of the novel antipsychotic cariprazine, a D3 -preferring dopamine D3 /D2 receptor partial agonist, on cholinergically induced gamma oscillations in rat hippocampal slices from treatment-naïve and MK-801-treated rats, a model of acute first-episode schizophrenia. Key results: The D3 receptor-preferring agonist pramipexole effectively decreased the power of gamma oscillations, while the D3 receptor antagonist SB-277011 had no effect. In treatment-naïve animals, cariprazine did not modulate strong gamma oscillations but slightly improved the periodicity of non-saturated gamma activity. Cariprazine showed a clear partial agonistic profile at D3 receptors at the network level by potentiating the inhibitory effects when the D3 receptor tone was low and antagonizing the effects when the tone was high. In hippocampal slices of MK-801-treated rats, cariprazine allowed stabilization of the aberrant increase in gamma oscillation power and potentiated resynchronization of the oscillations. Conclusion and implications: Data from this study indicate that cariprazine stabilizes pathological hippocampal gamma oscillations, presumably by its partial agonistic profile. The results demonstrate in vitro gamma oscillations as predictive biomarkers to study the effects of antipsychotics preclinically at the network level

X-ray radiation from ions with K-shell vacancies

Abstract New types of space resolved X-ray spectra produced in light matter experiments with high intensity lasers have been investigated experimentally and theoretically. This type of spectra is characterised by the disappearance of distinct resonance line emission and the appearance of very broad emission structures due to the dielectronic satellite transitions associated to the resonance lines. Atomic data calculations have shown, that rather exotic states with K-shell vacancies are involved. For quantitative spectra interpretation we developed a model for dielectronic satellite accumulation (DSA-model) in cold dense optically thick plasmas which are tested by rigorous comparison with space resolved spectra from ns-lasers. In experiments with laser intensities up to 10 19 W/cm 2 focused into nitrogen gas targets, hollow ion configurations are observed by means of soft X-ray spectroscopy. It is shown that transitions in hollow ions can be used for plasma diagnostic. The determination of the electron temperature in the long lasting recombining regime is demonstrated. In Light-matter interaction experiments with extremely high contrast (up to 10 10 ) short pulse (400 fs) lasers electron densities of n e ≈3×10 23 cm −3 at temperatures between kT e =200–300 eV have been determined by means of spectral simulations developed previously for ns-laser produced plasmas. Expansion velocities are determined analysing asymmetric optically thick line emission. Further, the results are checked by observing the spectral windows involving the region about the He α -line and the region from the He β -line to the He-like continuum. Finally, plasmas of solid density are characteristic in experiments with heavy ion beams heating massive targets. We report the first spectroscopic investigations in plasmas of this type with results on solid neon heated by Ar-ions. A spectroscopic method for the determination of the electron temperature in extreme optically thick plasmas is developed

Evidence-based hydro- and balneotherapy in Hungary-a systematic review and meta-analysis

Balneotherapy is appreciated as a traditional treatment modality in medicine. Hungary is rich in thermal mineral waters. Balneotherapy has been in extensive use for centuries and its effects have been studied in detail. Here, we present a systematic review and meta-analysis of clinical trials conducted with Hungarian thermal mineral waters, the findings of which have been published by Hungarian authors in English. The 122 studies identified in different databases include 18 clinical trials. Five of these evaluated the effect of hydro- and balneotherapy on chronic low back pain, four on osteoarthritis of the knee, and two on osteoarthritis of the hand. One of the remaining seven trials evaluated balneotherapy in chronic inflammatory pelvic diseases, while six studies explored its effect on various laboratory parameters. Out of the 18 studies, 9 met the predefined criteria for meta-analysis. The results confirmed the beneficial effect of balneotherapy on pain with weight bearing and at rest in patients with degenerative joint and spinal diseases. A similar effect has been found in chronic pelvic inflammatory disease. The review also revealed that balneotherapy has some beneficial effects on antioxidant status, and on metabolic and inflammatory parameters. Based on the results, we conclude that balneotherapy with Hungarian thermal-mineral waters is an effective remedy for lower back pain, as well as for knee and hand osteoarthritis. © 2013 The Author(s)

Capsaicin-Induced Changes in LTP in the Lateral Amygdala Are Mediated by TRPV1

The transient receptor potential vanilloid type 1 (TRPV1) channel is a well recognized polymodal signal detector that is activated by painful stimuli such as capsaicin. Here, we show that TRPV1 is expressed in the lateral nucleus of the amygdala (LA). Despite the fact that the central amygdala displays the highest neuronal density, the highest density of TRPV1 labeled neurons was found within the nuclei of the basolateral complex of the amygdala. Capsaicin specifically changed the magnitude of long-term potentiation (LTP) in the LA in brain slices of mice depending on the anesthetic (ether, isoflurane) used before euthanasia. After ether anesthesia, capsaicin had a suppressive effect on LA-LTP both in patch clamp and in extracellular recordings. The capsaicin-induced reduction of LTP was completely blocked by the nitric oxide synthase (NOS) inhibitor L-NAME and was absent in neuronal NOS as well as in TRPV1 deficient mice. The specific antagonist of cannabinoid receptor type 1 (CB1), AM 251, was also able to reduce the inhibitory effect of capsaicin on LA-LTP, suggesting that stimulation of TRPV1 provokes the generation of anandamide in the brain which seems to inhibit NO synthesis. After isoflurane anesthesia before euthanasia capsaicin caused a TRPV1-mediated increase in the magnitude of LA-LTP. Therefore, our results also indicate that the appropriate choice of the anesthetics used is an important consideration when brain plasticity and the action of endovanilloids will be evaluated. In summary, our results demonstrate that TRPV1 may be involved in the amygdala control of learning mechanisms

EQ-5D in Central and Eastern Europe : 2000-2015

Objective: Cost per quality-adjusted life year data are required for reimbursement decisions in many Central and Eastern European (CEE) countries. EQ-5D is by far the most commonly used instrument to generate utility values in CEE. This study aims to systematically review the literature on EQ-5D from eight CEE countries. Methods: An electronic database search was performed up to July 1, 2015 to identify original EQ-5D studies from the countries of interest. We analysed the use of EQ-5D with respect to clinical areas, methodological rigor, population norms and value sets. Results: We identified 143 studies providing 152 country-specific results with a total sample size of 81,619: Austria (n=11), Bulgaria (n=6), Czech Republic (n=18), Hungary (n=47), Poland (n=51), Romania (n=2), Slovakia (n=3) and Slovenia (n=14). Cardiovascular (20%), neurologic (16%), musculoskeletal (15%) and endocrine/nutritional/metabolic diseases (14%) were the most frequently studied clinical areas. Overall 112 (78%) of the studies reported EQ VAS results and 86 (60%) EQ-5D index scores, of which 27 (31%) did not specify the applied tariff. Hungary, Poland and Slovenia have population norms. Poland and Slovenia also have a national value set. Conclusions: Increasing use of EQ-5D is observed throughout CEE. The spread of health technology assessment activities in countries seems to be reflected in the number of EQ-5D studies. However, improvement in informed use and methodological quality of reporting is needed. In jurisdictions where no national value set is available, in order to ensure comparability we recommend to apply the most frequently used UK tariff. Regional collaboration between CEE countries should be strengthened

Depth resolved comparative investigation of phase formation and stress build-up in cubic boron nitride films

Cubic boron nitride films have been deposited by means of ion beam assisted deposition (IBAD) and electron cyclotron resonance plasma CVD. Specially designed silicon cantilever substrates were used which allow precise stress measurements. After deposition, the films were etched back in steps of approximately 5-20 nm by Ar ions. After each step, the stress, the thickness and also FTIR spectra were measured. By this means, the stress distribution, the development of the c-BN content and also the thicknesses of the h-BN nucleation layer and the transition layer h-BN --> c-BN could be determined. Major differences were found between the two types of layers: IBAD films possess a nucleation layer with a thickness of 15-20 nm and a stress of approximately 3 GPa. After c-BN nucleation, a transition region of approximately 20 nm is observed in which the c-BN content rapidly increases to the final value, which can exceed 90%. However, the c-BN top layer possesses a high compressive stress with values up to 20 GPa. In contrast, for ECR films the transition from the h-BN nucleation layer to the c-BN top layer is much more gradual (nucleation layer thickness approx. 50 nm). Simultaneously, the c-BN content of the top layer is limited to approximately 70% while its stress is much lower (2-3 GPa). The reasons for these differences in phase formation and stress build-up are discussed in terms of the differences between the two techniques. (C) 2001 Elsevier Science B.V. All rights reserved.28th International Conference on Metallurgia; San Diego,CA; United States; 30 April 2001 through 30 May 2001.SCOPUS: ar.jinfo:eu-repo/semantics/publishe