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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.

We have previously developed quinolone-3-carboxamides with the aim of obtaining new ligands for both cannabinoid receptors, CB1 and CB2. Our preliminary screening led to the identification of cannabinoid receptor ligands characterized by high affinity and, in some cases, also selectivity for CB(2) receptors. Specifically, three compounds, 1, 2 and 3 showed high affinity for CB2 as well as high selectivity over CB1 receptors. In addition, the activity shown by 1 against the formalin-induced nocifensive response in mice, reported in our previous paper, suggests that quinolone-3-carboxamides possess anti-nociceptive properties. In the present work, we have performed functional in vitro bioassays with the aim of investigating the functional activity in the [35S]GTPgammaS binding assay of the other two compounds that, like 1, behave as CB2 selective ligands, and their potential analgesic actions in vivo. We found that both 2 and 3 behave in vitro as CB2 inverse agonists and are able to decrease nociceptive behaviour in the late phase of the formalin test only at the highest dose tested, although, at lower doses, they prevent the anti-nociceptive effects of a selective CB2 partial agonist in the formalin test. These results identify in 2 and 3 two novel, potent and selective CB2 antagonists/inverse agonists and confirm previous reports in the literature that, in addition to agonists at cannabinoid CB2 receptors, also inverse agonists/antagonists at these receptors show promise as anti-inflammatory agents.

Background and Objective: Milk production and cheese industries need to balance the genetic progress in milk yield and protein content with the need for improving milk coagulation properties and workability. Our objective was to determine how rapidly and to what extent Milk Clotting Properties (MCP) could be improved by using Embryo Transfer (ET) to increase the frequency of the κ-casein BB genotype and reducing A and E variants in an Italian Holstein herd with a low prevalence of the favorable genotype. Materials and Methods: In a herd of 352 cows, with a relatively low distribution of the favorable κ-casein BB genotype (11.0%) and poor milk clotting properties, κ-casein BB animals were superovulated (36 out of 39) and bred with SexedULTRA™ sex-sorted semen of κ-casein BB bulls in order to improve milk workability and cheese yield. Forty-five embryo transfer sessions yielded 203 embryos, 108 pregnancies and 98 females, of which 89 calved and entered the first lactation. Results: Milk composition and coagulation properties differed significantly among the groups considered (p

Contents The objective was to compare embryo yield and quality in lactating dairy cows superovulated (SO) with varying amounts of gonadotropins and FSH:LH ratios and inseminated with SexedULTRA (TM) sex-sorted semen. The SO treatments (n = 77) involved 3 protocols: groups F700 and F1000 were given total doses of 700 and 1,000 IU of Folltropin (FSH:LH ratio 49:1), respectively, whereas group F700P300 was given 700 IU of Folltropin + 300 IU of Pluset (FSH:LH ratio 1:1). Cows were artificially inseminated 3 times over a 10-hr interval with frozen-thawed SexedULTRA (TM) sex-sorted semen (total of 10 x 10(6) sex-sorted sperm), starting 18 hr after onset of oestrus, with embryos/ova recovered 7 d after oestrus. Total number of recovered structures and transferable embryos were lower (p < 0.05) in F700 (4.7 +/- 3.0 and 1.9 +/- 1.7, respectively; mean +/- SD) compared to F1000 (8.1 +/- 3.8 and 4.4 +/- 2.6) and F700P300 (8.5 +/- 6.4 and 4.5 +/- 3.3). Percentage of cows ovulating >50% of follicles >= 0.8 cm in diameter was lower (p < 0.05) in F700 (35.5%) than in F1000 (82.4%) and F700P300 (73.1%). Percentage of unfertilized oocytes was higher (p < 0.05) in F700 (45.0% vs. 27.7% for F1000 and 29.0% for F700P300) whereas percentage of morulae was higher (p < 0.05) in F1000 (19.3% vs. 8.7% for F700 and 12.2% for F700P300). Embryo quality was similar among groups (p > 0.05). In conclusion, embryo production in lactating dairy cows was improved by increasing total dose of gonadotropins from 700 to 1,000 IU, with SexedULTRA (TM) sex-sorted semen yielding satisfactory fertilization rates and embryo quality.

A set of quinolone-3-carboxamides 2 bearing diverse substituents at position 1, 3, and 6 of the bicyclic nucleus was prepared. Except for six compounds exhibiting Ki > 100 nM, all the quinolone-3-carboxamides 2 proved to be high affinity CB2 ligands, with Ki values ranging from 73.2 to 0.7 nM and selectivity [SI = Ki(CB1)/Ki(CB2)] varying from >14285 to 1.9, with only 2ah exhibiting a reverse selectivity (SI < 1). In the formalin test of peripheral acute and inflammatory pain in mice, 2ae showed analgesic activity that was antagonized by a selective CB2 antagonist. By contrast, 2e was inactive per se and antagonized the effect of a selective CB2 agonist. Finally, 2g and 2p exhibited CB2 inverse agonist-like behavior in this in vivo test. However, two different functional assays carried out in vitro on 2e and 2g indicated for both compounds an overall inverse agonist activity at CB2 receptors. © 2010 American Chemical Society.

Background and purpose: The phytocannabinoid, Δ 9- tetrahydrocannabivarin (THCV), can block cannabinoid CB 1 receptors. This investigation explored its ability to activate CB 2 receptors, there being evidence that combined CB 2 activation/CB 1 blockade would ameliorate certain disorders. Experimental approach: We tested the ability of THCV to activate CB 2 receptors by determining whether: (i) it inhibited forskolin-stimulated cyclic AMP production by Chinese hamster ovary (CHO) cells transfected with human CB 2 (hCB 2) receptors; (ii) it stimulated [ 35S]GTPγS binding to hCB 2 CHO cell and mouse spleen membranes; (iii) it attenuated signs of inflammation/hyperalgesia induced in mouse hind paws by intraplantar injection of carrageenan or formalin; and (iv) any such anti-inflammatory or anti-hyperalgesic effects were blocked by a CB 1 or CB 2 receptor antagonist. Key results: THCV inhibited cyclic AMP production by hCB 2 CHO cells (EC 50 = 38 nM), but not by hCB 1 or untransfected CHO cells or by hCB 2 CHO cells pre-incubated with pertussis toxin (100 ng·mL -1) and stimulated [ 35S]GTPγS binding to hCB 2 CHO and mouse spleen membranes. THCV (0.3 or 1 mg·kg -1 i.p.) decreased carrageenan-induced oedema in a manner that seemed to be CB 2 receptor-mediated and suppressed carrageenan-induced hyperalgesia. THCV (i.p.) also decreased pain behaviour in phase 2 of the formalin test at 1 mg·kg -1, and in both phases of this test at 5 mg·kg -1; these effects of THCV appeared to be CB 1 and CB 2 receptor mediated. Conclusions and implications: THCV can activate CB 2 receptors in vitro and decrease signs of inflammation and inflammatory pain in mice partly via CB 1 and/or CB 2 receptor activation. © 2010 The British Pharmacological Society All rights reserved.