Orientational Coherent Effects of High-Energy Particles in a LiNbO3 Crystal.

A bent lithium niobate strip was exposed to a 400-GeV/c proton beam at the external lines of CERN Super Proton Synchrotron to probe its capabilities versus coherent interactions of the particles with the crystal such as channeling and volume reflection. Lithium niobate (LiNbO3) exhibits an interplanar electric field comparable to that of Silicon (Si) and remarkable piezoelectric properties, which could be exploited for the realization of piezo-actuated devices for the control of high-energy particle beams. In contrast to Si and germanium (Ge), LiNbO3 shows an intriguing effect; in spite of a low channeling efficiency (3%), the volume reflection maintains a high deflection efficiency (83%). Such discrepancy was ascribed to the high concentration (10(4) per cm2) of dislocations in our sample, which was obtained from a commercial wafer. Indeed, it has been theoretically shown that a channeling efficiency comparable with that of Si or Ge would be attained with a crystal at low defect concentration (less than ten per cm2). To better understand the role of dislocations on volume reflection, we have worked out computer simulation via dynecharm++ Monte Carlo code to study the effect of dislocations on volume reflection. The results of the simulations agree with experimental records, demonstrating that volume reflection is more robust than channeling in the presence of dislocations.

Medical cannabis vs. synthetic cannabinoids: What does the future hold?

The medical use of cannabis has an intricate therapeutic history that finds its roots in ancient China (∼2700 BC). The main psychoactive component of cannabis, Δ(9) -tetrahydrocannabinol (Δ(9) -THC), was discovered in 1964. This was a significant breakthrough, as it allowed the generation of synthetic analogs of Δ(9) -THC, the discovery of cannabinoid receptors, and the generation of synthetic small molecules. Despite this, today there is still a paucity of drugs that target the cannabinoid system.

Cannabidiolic acid prevents vomiting in Suncus murinus and nausea-induced behaviour in rats by enhancing 5-HT1A receptor activation.

BACKGROUND AND PURPOSE: To evaluate the ability of cannabidiolic acid (CBDA) to reduce nausea and vomiting and enhance 5-HT(1A) receptor activation in animal models. EXPERIMENTAL APPROACH: We investigated the effect of CBDA on (i) lithium chloride (LiCl)-induced conditioned gaping to a flavour (nausea-induced behaviour) or a context (model of anticipatory nausea) in rats; (ii) saccharin palatability in rats; (iii) motion-, LiCl- or cisplatin-induced vomiting in house musk shrews (Suncus murinus); and (iv) rat brainstem 5-HT(1A) receptor activation by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and mouse whole brain CB(1) receptor activation by CP55940, using [³5S]GTPγS-binding assays. KEY RESULTS: In shrews, CBDA (0.1 and/or 0.5 mg·kg⁻¹ i.p.) reduced toxin- and motion-induced vomiting, and increased the onset latency of the first motion-induced emetic episode. In rats, CBDA (0.01 and 0.1 mg·kg⁻¹ i.p.) suppressed LiCl- and context-induced conditioned gaping, effects that were blocked by the 5-HT(1A) receptor antagonist, WAY100635 (0.1 mg·kg⁻¹ i.p.), and, at 0.01 mg·kg⁻¹ i.p., enhanced saccharin palatability. CBDA-induced suppression of LiCl-induced conditioned gaping was unaffected by the CB1 receptor antagonist, SR141716A (1 mg·kg⁻¹ i.p.). In vitro, CBDA (0.1-100 nM) increased the E(max) of 8-OH-DPAT. CONCLUSIONS AND IMPLICATIONS: Compared with cannabidiol, CBDA displays significantly greater potency at inhibiting vomiting in shrews and nausea in rats, and at enhancing 5-HT(1A) receptor activation, an action that accounts for its ability to attenuate conditioned gaping in rats. Consequently, CBDA shows promise as a treatment for nausea and vomiting, including anticipatory nausea for which no specific therapy is currently available.

Cannabidiol, a non-psychotropic component of cannabis, attenuates vomiting and nausea-like behaviour via indirect agonism of 5-HT(1A) somatodendritic autoreceptors in the dorsal raphe nucleus.

BACKGROUND AND PURPOSE: To evaluate the hypothesis that activation of somatodendritic 5-HT(1A) autoreceptors in the dorsal raphe nucleus (DRN) produces the anti-emetic/anti-nausea effects of cannabidiol (CBD), a primary non-psychoactive cannabinoid found in cannabis. EXPERIMENTAL APPROACH: The potential of systemic and intra-DRN administration of 5-HT(1A) receptor antagonists, WAY100135 or WAY100635, to prevent the anti-emetic effect of CBD in shrews (Suncus murinus) and the anti-nausea-like effects of CBD (conditioned gaping) in rats were evaluated. Also, the ability of intra-DRN administration of CBD to produce anti-nausea-like effects (and reversal by systemic WAY100635) was assessed. In vitro studies evaluated the potential of CBD to directly target 5-HT(1A) receptors and to modify the ability of the 5-HT(1A) agonist, 8-OH-DPAT, to stimulate [(35) S]GTPγS binding in rat brainstem membranes. KEY RESULTS: CBD suppressed nicotine-, lithium chloride (LiCl)- and cisplatin (20 mg·kg(-1) , but not 40 mg·kg(-1) )-induced vomiting in the S. murinus and LiCl-induced conditioned gaping in rats. Anti-emetic and anti-nausea-like effects of CBD were suppressed by WAY100135 and the latter by WAY100635. When administered to the DRN: (i) WAY100635 reversed anti-nausea-like effects of systemic CBD, and (ii) CBD suppressed nausea-like effects, an effect that was reversed by systemic WAY100635. CBD also displayed significant potency (in a bell-shaped dose-response curve) at enhancing the ability of 8-OH-DPAT to stimulate [(35) S]GTPγS binding to rat brainstem membranes in vitro. Systemically administered CBD and 8-OH-DPAT synergistically suppressed LiCl-induced conditioned gaping. CONCLUSIONS AND IMPLICATIONS: These results suggest that CBD produced its anti-emetic/anti-nausea effects by indirect activation of the somatodendritic 5-HT(1A) autoreceptors in the DRN. LINKED ARTICLES: This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7.

Observation of multiple volume reflection of ultrarelativistic protons by a sequence of several bent silicon crystals.

The interactions of 400 GeV protons with different sequences of bent silicon crystals have been investigated at the H8 beam line of the CERN Super Proton Synchrotron. The multiple volume reflection of the proton beam has been studied in detail on a five-crystal reflector measuring an angular beam deflection theta = 52.96 +/- 0.14 microrad. The efficiency was found larger than 80% for an angular acceptance at the reflector entrance of 70 microrad, with a maximal efficiency value of epsilon = 0.90 +/- 0.01 +/- 0.03.

Volume reflection dependence of 400 GeV/c protons on the bent crystal curvature.

The trend of volume reflection parameters (deflection angle and efficiency) in a bent (110) silicon crystal has been investigated as a function of the crystal curvature with 400 GeV/c protons on the H8 beam line at the CERN Super Proton Synchrotron. This Letter describes the analysis performed at six different curvatures showing that the optimal radius for volume reflection is approximately 10 times greater than the critical radius for channeling. A strong scattering of the beam by the planar potential is also observed for a bend radius close to the critical one.

Setting the conditions for efficient, robust and reproducible generation of functionally active neurons from adult subventricular zone-derived neural stem cells.

Although new culture conditions enable homogeneous and long-term propagation of radial glia-like neural stem (NS) cells in monolayer and serum-free conditions, the efficiency of the conversion of NS cells into terminally differentiated, functionally mature neurons is relatively limited and poorly characterized. We demonstrate that NS cells derived from adult mouse subventricular zone robustly develop properties of mature neurons when exposed to an optimized neuronal differentiation protocol. A high degree of cell viability was preserved. At 22 days in vitro, most cells (65%) were microtubule-associated protein 2(+) and coexpressed gamma-aminobutyric acid (GABA), GAD67, calbindin and parvalbumin. Nearly all neurons exhibited sodium, potassium and calcium currents, and 70% of them fired action potentials. These neurons expressed functional GABA(A) receptors, whereas activable kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-D-aspartic acid receptors were present in approximately 80, 30 and 2% of cells, respectively. Antigenic and functional properties were efficiently and reliably reproduced across experiments and cell passages (up to 68). This is the first report showing a consistent and reproducible generation of large amounts of neurons from long-term passaged adult neural stem cells. Remarkably, the neuronal progeny carries a defined set of antigenic, biochemical and functional characteristics that make this system suitable for studies of NS cell biology as well as for genetic and chemical screenings.