Will the new CB1 cannabinoid receptor antagonist SR-147778 have advantages over rimonabant?

Obesity and alcoholism are two common modern-day diseases. The cannabinoid CB, receptor antagonist rimonabant is in Phase III clinical trial for the treatment of obesity with preliminary results showing that it decreases appetite and body weight. Animal studies have shown that rimonabant is effective in the treatment of alcoholism. SR-147778 is a new potent and selective CB1 receptor antagonist. In animals, SR-147778 has been shown to inhibit CB1 receptor-mediated hypothermia, analgesia and slowing of gastrointestinal transit. In rats trained to drink sucrose, the oral administration of SR-147778 3 mg/kg, before the presentation of sucrose, decreased the consumption of sucrose. SR-147778 3 mg/kg also reduced spontaneous feeding in rats deprived of food and also in non-deprived rats. In Sardinian alcohol-preferring (sP) rats, in the alcohol-naive state, SR-147778 slowed the development of a preference for alcohol. in alcohol-experienced sP rats SR-147778 (2.5, 5 and 10 mg/kg p.o.) reduced the alcohol intake. When alcohol-experienced sP rats are deprived of alcohol for 15 days, there is a large intake of alcohol on reintroduction of alcohol, and this response was almost abolished by treatment with SR-147778. From the preclinical studies published to date, there is no obvious major point of difference between rimonabant and SR-147778, and both are promising agents for the treatment of obesity and alcoholism.

Behavioral Profile of the Novel Cannabinoid Agonist AM4054

Although cannabinoid drugs have been used for thousands of years both recreationally and therapeutically, little has been known about their mechanisms of action until recently. Since the discovery of the endogenous cannabinoid CB1 receptor in 1988, the behavioral profile of cannabinoid receptor ligands has been much more thoroughly defined. Cannabinoid CB1 agonists have been shown to produce a variety of behavioral effects including suppression of locomotion, catalepsy, hypothermia, and analgesia. Research has also demonstrated that these behavioral effects can be inhibited by CB1 receptor antagonists including SR 141716 and AM 251. Although behavioral indicators of anxiety including thigmotaxis have been observed in several different paradigms, there is inconclusive and often times contradictory evidence to define the role of anxiety in CB1 receptor activation. The present study addressed the behavioral profile of AM 4054, a novel full agonist at the CB1 receptor, as well as the ability of the CB1 antagonist AM 251 to reverse these effects. To further identify and expand research on the suppression of locomotion and induction of thigmotaxis with the administration of a CB1 agonist, experiment 1 was conducted in the open field. In this experiment, each rat (n=40) was randomly assigned one of the five treatments: vehicle, 0.16, 0.32, 0.64, or 1.25 mg/kg AM 4054. After a 30 minute pre-treatment, each subject was tested in the open field for 18 minutes. Results indicated that AM 4054 produced a dose-related suppression of locomotion as well as the subtle presence of thigmotaxis in two out of four doses. In experiment 2, subjects (n=40) received either vehicle or 2.0 or 4.0 mg/kg AM 251 60 minutes prior to testing. After 30 minutes, the subjects were given either a 0.3 mg/kg dose of AM 4054 or vehicle. After a total pretreatment duration of 60 minutes, the animals were tested on a battery of tasks including an 18 minute session in locomotor boxes. Experiment 2 was a continuation of a previous study conducted in the same lab, which confirmed the effects of AM 4054 on this tetrad of tasks as being consistent with other cannabinoid agonists. In this experiment the effects of AM 4054 were reversed by the administration of the CB1 antagonist AM 251. Past studies have shown that AM 4054 is a highly potent drug with behavioral actions similar to other cannabinoid CB1 agonists. Furthermore, AM 4054 can be a useful drug in future studies, and has potential therapeutic value for the treatment of various conditions.

Analytical procedures for determining Pb and Sr isotopic compositions in water samples by ID-TIMS

Few articles deal with lead and strontium isotopic analysis of water samples. The aim of this study was to define the chemical procedures for Pb and Sr isotopic analyses of groundwater samples from an urban sedimentary aquifer. Thirty lead and fourteen strontium isotopic analyses were performed to test different analytical procedures. Pb and Sr isotopic ratios as well as Sr concentration did not vary using different chemical procedures. However, the Pb concentrations were very dependent on the different procedures. Therefore, the choice of the best analytical procedure was based on the Pb results, which indicated a higher reproducibility from samples that had been filtered and acidified before the evaporation, had their residues totally dissolved, and were purified by ion chromatography using the Biorad® column. Our results showed no changes in Pb ratios with the storage time.

Logarithmic contribution to the electrical resistivity in (Ru(1-x)Ir(x))Sr(2)GdCu(2)O(8) compounds

A systematic study of magnetoresistance and dc magnetization was conducted in polycrystalline (Ru(1-x)Ir(x))Sr(2)GdCu(2)O(8) [(Ru,Ir)-1212] compounds, for 0 <= x <= 0.15. We found that a deviation from linearity in the normal-state electrical resistivity (rho) curves for temperatures below the magnetic transition temperature T(M) < 130 K can be properly described by a logarithmic term. The prefactor C(x, H) of this anomalous ln T contribution to rho(T) increases linearly with the Ir concentration, and diminishes rapidly with increasing applied magnetic field up to H approximate to 4 T, merging with the C(0,H) curve at higher magnetic fields. Correlation with magnetic susceptibility measurements supports a scenario of local perturbations in the orientation of Ru moments induced in the neighborhood of the Ir ions, therefore acting as scattering centers. The linear dependence of the prefactor C(x,H=0) and the superconducting transition temperature T(SC) on x points to a common source for the resistivity anomaly and the reduction in T(SC), suggesting that the CuO(2) and RuO(2) layers are not decoupled.

Transport Barkhausen-like noise in uniaxially pressed Bi(1.65)Pb(0.35)Sr(2)Ca(2)Cu(3)O(10+delta) ceramic samples

We report on the detection of the transport Barkhausen-like noise (TBN) in polycrystalline samples of Bi(1.65)Pb(0.35)Sr(2)Ca(2) Cu(3)O(10+delta) (Bi-2223) which were subjected to different uniaxial compacting pressures. The transport Barkhausen-like noise was measured when the sample was subjected to an ac triangular-shape magnetic field (f similar to 1 Hz) with maximum amplitude B(max) approximate to 5.5 mT, in order to avoid the flux penetration within the superconducting grains. Analysis of the TBN signal, measured for several values of excitation current density, indicated that the applied magnetic field in which the noise signal first appears, B(a)(t(i)), is closely related to the magnetic-flux pinning capability of the material. The combined results are consistent with the existence of three different superconducting levels within the samples: (i) the superconducting grains; (ii) the superconducting clusters; and (iii) the weak-links. We finally argue that TBN measurements constitute a powerful tool for probing features of the intergranular transport properties in polycrystalline samples of high-T(c) superconductors. (C) 2010 Elsevier B.V. All rights reserved.

Experimental and theoretical study of transport properties in uniaxially pressed (Bi, Pb)(2)Sr(2)Ca(2)Cu(3)O(10+delta) ceramic samples

Experimental and theoretical studies on the magnetic field dependence of the electrical resistance R(B(a)) and the transport noise (TN) in polycrystalline high-T(c) superconductors subjected to different uniaxial compacting pressures were conducted. X-ray diffraction rocking curves were performed in different surfaces of the samples in order to investigated the degree of texture The results indicated an improvement of the degree of texture with increasing the uniaxial compacting pressure In theoretical simulations of the data, the polycrystalline superconductors were described as a series-parallel array of Josephson devices The intergranular magnetic field is described within the framework of the intragranular flux-trapping model and the distribution of the grain-boundary angles is assumed to follow the Rayleigh statistical function The proposed model describes well the experimental magnetoresistance R(B(a)) data We have found that the behavior of the R(B(a)) curves changes appreciably when different uniaxially compacting pressures are applied to the sample and such a changes are reproduced by the model when different grain-boundary angles distributions are used In addition, changes in the R(B(a)) dependence have their counterparts in the experimental transport noise signals (C) 2009 Elsevier B.V. All rights reserved

Deconvolving the delta O-18 seawater component from subseasonal coral delta O-18 and Sr/Ca at Rarotonga in the southwestern subtropical Pacific for the period 1726 to 1997

To reconstruct oceanographic variations in the subtropical South Pacific, 271-year long subseasonal time series of Sr/Ca and delta(18)O were generated from a coral growing at Rarotonga (21.5degreesS, 159.5degreesW). In this case, coral Sr/Ca appears to be an excellent proxy for sea surface temperature (SST) and coral delta(18)O is a function of both SST and seawater delta(18)O composition (delta(18)O(sw)). Here, we focus on extracting the delta(18)O(sw) signal from these proxy records. A method is presented assuming that coral Sr/Ca is solely a function of SST and that coral delta(18)O is a function of both SST and delta(18)O(sw). This method separates the effects of delta(18)O(sw) from SST by breaking the instantaneous changes of coral delta(18)O into separate contributions by instantaneous SST and delta(18)O(sw) changes, respectively. The results show that on average delta(18)O(sw) at Rarotonga explains similar to39% of the variance in delta(18)O and that variations in SST explains the remaining similar to61% of delta(18)O variance. Reconstructed delta(18)O(sw) shows systematic increases in summer months (December-February) consistent with the regional pattern of variations in precipitation and evaporation. The delta(18)O(sw) also shows a positive linear correlation with satellite-derived estimated salinity for the period 1980 to 1997 (r = 0.72). This linear correlation between reconstructed delta(18)O(sw) and salinity makes it possible to use the reconstructed delta(18)O(sw) to estimate the past interannual and decadal salinity changes in this region. Comparisons of coral delta(18)O and delta(18)O(sw) at Rarotonga with the Pacific decadal oscillation index suggest that the decadal and interdecadal salinity and SST variability at Rarotonga appears to be related to basin-scale decadal variability in the Pacific. Copyright (C) 2002 Elsevier Science Ltd.

Luminescent and morphological study of Sr(2)CeO(4) blue phosphor prepared from oxalate precursors

Luminescent and morphological studies of Sr(2)CeO(4) blue phosphor prepared from cerium-doped strontium oxalate precursor are reported Powder samples were prepared from 5 and 25 mol% Ce(3+)-doped strontium oxalate as well as from a mechanical mixture of strontium oxalate and cerium oxalate at a 4 1 ratio respectively All the samples were characterized by XRD IR PLS and SEM The luminescent and structural properties of the Sr(2)CeO(4) material are little affected by the SrCO(3) remaining from precursors The Sr(2)CeO(4) material consists in one-dimensional chains of edge-sharing CeO(6) octahedra that are linked together by Sr(2+) ions The carbonate ion might be associated with oxygen ions of the linear chain and also with the oxygen atoms located in the equatorial position which consequently affects the charge transfer bands between O(2-) and Ce(4+). As observed by SEM, the morphological changes are related to each kind of precursor and thermal treatment along with irregular powder particles within the size range 05-2 mu m (c) 2010 Elsevier B V All rights reserved

Arginine methylation analysis of the splicing-associated SR protein SFRS9/SRP30C

The human SFRS9/SRp30c belongs to the SR family of splicing regulators. Despite evidence that members of this protein family may be targeted by arginine methylation, this has yet to be experimentally addressed. In this study, we found that SFRS9 is a target for PRMT1-mediated arginine methylation in vitro, and that it is immunoprecipitated from HEK-293 lysates by antibodies that recognize both mono- and dimethylated arginines. We further observed that upon treatment with the methylation inhibitor Adox, the fluorescent EGFP-SFRS9 re-localizes to dot-like structures in the cell nucleus. In subsequent confocal analyses, we found that EGFP-SFRS9 localizes to nucleoli in Adox-treated cells. Our findings indicate the importance of arginine methylation for the subnuclear localization of SFRS9.

Determination of eutectic solidification mode in Sr-modified hypoeutectic Al-Si alloys by EBSD

The effect of eutectic modification by strontium on nucleation and growth of the eutectic in hypoeutectic Al-Si foundry alloys has been investigated by electron back-scattering diffraction (EBSD) mapping. Specimens were prepared from three hypoeutectic AlSi base alloys with 5, 7 and 10 mass%Si and with different strontium contents up to 740 ppm for modification of eutectic silicon. By comparing the orientation of the aluminium in the eutectic to that of the surrounding primary aluminium dendrites? the growth mode of the eutectic could be determined. The mapping results indicate that the eutectic grew from the primary phase in unmodified alloys. When the eutectic was modified by strontium, eutectic grains nucleated separately from the primary dendrites. However, in alloys with high strontium levels, the eutectic again grew from the primary phase. These observed effects of strontium additions on the eutectic solidification mode are independent of silicon content in the range between 5 and 10 mass%Si.

Mantle source heterogeneity, magma generation and magmatic evolution at Terceira Island (Azoresarchipelago): Constraints from elemental and isotopic (Sr, Nd, Hf, and Pb) data

This work addresses the present-day (<100 ka) mantle heterogeneity in the Azores region through the study of two active volcanic systems from Terceira Island. Our study shows that mantle heterogeneities are detectable even when "coeval" volcanic systems (Santa Barbara and Fissural) erupted less than 10 km away. These volcanic systems, respectively, reflect the influence of the Terceira and D. Joao de Castro Bank end-members defined by Beier et at (2008) for the Terceira Rift Santa Barbara magmas are interpreted to be the result of mixing between a HIMU-type component, carried to the upper mantle by the Azores plume, and the regional depleted MORB magmas/source. Fissural lavas are characterized by higher Ba/Nb and Nb/U ratios and less radiogenic Pb-206/Pb-204, Nd-143/Nd-144 and Hf-176/Hf-177, requiring the small contribution of delaminated sub-continental lithospheric mantle residing in the upper mantle. Published noble gas data on lavas from both volcanic systems also indicate the presence of a relatively undegassed component, which is interpreted as inherited from a lower mantle reservoir sampled by the ascending Azores plume. As inferred from trace and major elements, melting began in the garnet stability field, while magma extraction occurred within the spinel zone. The intra-volcanic system's chemical heterogeneity is mainly explained by variable proportions of the above-mentioned local end-members and by crystal fractionation processes. (C) 2011 Elsevier By. All rights reserved.