Kavapyrone enriched extract from Piper methysticum as modulator of the GABA binding site in different regions of rat brain

Regional differences in the modulation of [3H] muscimol binding to GABAA receptor complexes by kavapyrones, compounds of the rhizome of the plant Piper methysticum which possess sedative activity, were demonstrated using membrane fractions obtained from target brain centers of kavapyrone action: hippocampus (HIP), amygdala (AMY) and medulla oblongata (MED), and from brain centers outside the main kavapyrone effects as frontal cortex (FC) and cerebellum (CER). The kava extract enhanced the binding of [3H] muscimol in a concentration-dependent manner with maximal potentiation of 358% over control in HIP followed by AMY and MED (main target brain centers). Minimal stimulation was observed in CER followed by FC. In contrast, apart from CER, the potency of kavapyrones was similar in the brain areas investigated with EC50 values ranging between 200 and 300 microM kavapyrones. Scatchard analysis revealed that the observed effects of kavapyrones were due to an increase in the number of binding sites (Bmax), rather than to a change in affinity. At a kavapyrone concentration of 500 microM the order of enhancement in Bmax was HIP = AMY > MED > FC > CER. When kavapyrones are included together with pentobarbital or HPO the two classes of compounds produced a more than additive, i.e., synergetic effect on [3H] muscimol binding. Our findings suggest that one way kavapyrones might mediate sedative effects in vivo is through effects on GABAA receptor binding.     

Effect of cisplatin and c-myb antisense phosphorothioate oligodeoxynucleotides combination on a human colon carcinoma cell line in vitro and in vivo

We investigated the effect of c-myb antisense phosphorothioate oligodeoxynucleotides [(S)ODNs] and cisplatin (CDDP) combination on the human colon carcinoma cell line LoVo Dx both in vitro and in nude mice bearing LoVo Dx solid tumour. We show that antisense (S)ODN treatment decreases c-myb mRNA and protein expression, induces growth arrest in the G1 phase of the cell cycle, and inhibits cell proliferation. In vivo treatment with c-myb antisense (S)ODNs results in a reduction in tumour growth. A greater inhibition of cell proliferation in vitro and a higher increase of tumour growth inhibition and growth delay in vivo were obtained with the combination of (S)ODNs and CDDP than when the two agents were administered separately. This comparative study, using the same tumour cell line in vitro and in vivo, suggests that c-myb antisense (S)ODNs might be useful in the therapy of colon cancer in combination with antineoplastic drugs.     

Trp82 and Tyr332 are involved in two quaternary ammonium binding domains of human butyrylcholinesterase as revealed by photoaffinity labeling with [3H]DDF

Purified butyrylcholinesterase (BuChE) was photolabeled by [3H]-p-N, N-dimethylamino benzene diazonium ([3H]DDF) to identify the quaternary ammonium binding sites on this protein [Ehret-Sabatier, L. , Schalk, I., Goeldner, M., and Hirth, C. (1992) Eur. J. Biochem. 203, 475-481]. The covalent photoincorporation occurs with a stoichiometry of one mole of probe per mole of inactivated site and could be fully prevented by several cholinergic inhibitors such as tacrine or tetramethylammonium. After complete deglycosylation of the enzyme using N-glycosidase F, the alkylated protein was trypsinolyzed and the digests were analyzed by HPLC coupled to ES-MS. A direct comparison of tryptic fragments from labeled and unlabeled BuChE allowed us to identify the tryptic peptide Tyr61-Lys103 as carrying the probe. Purification of the labeled peptides by anion-exchange chromatography gave a major radioactive peak which was further fractionated by reversed-phase HPLC leading to three, well-resolved, radioactive peaks. Microsequencing revealed that two of these peaks contained an overlapping sequence starting at Tyr61, while the third peak contained a sequence extending from Thr315. Radioactive signals could be unambiguously attributed to positions corresponding to residues Trp82 and Tyr332. This labeling study establishes the existence of two different binding domains for quaternary ammonium in BuChE and exemplifies additional cation/pi interactions in cholinergic proteins. This work strongly supports the existence of a peripheral anionic site in BuChE, implying residue Tyr332 as a key element.     

Computation of Wechsler Adult Intelligence Scale—Revised factor scores: Equal and differential weights.

Standard procedures for estimating factor scores for the Wechsler Adult Intelligence Scale—Revised (WAIS—R; D. Wechsler, 1981) involve equally weighted sums of the subtests that load most highly on the factor being estimated. We argue that factor scores derived in this manner lack discriminant validity; they are strongly biased toward g (the first unrotated factor) and away from the other 2 unrotated factors. If regression-like weights are applied to all of the WAIS—R subtests and the products are summed, the resulting differentially weighted factors give results that show similar convergent validity and much greater discriminant validity with respect to the original factors. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

The potential for energy efficiency in electric end usetechnologies

The authors summarize a recent study conducted by the Electric Power research Institute (EPRI) that contains estimates of potential energy savings that will result if the most efficient electricity technologies readily available immediately attain complete market saturation in the year 2000. They first define and contrast various efficiency scenarios and then summarize the energy savings forecast associated with demand-side management measured by sector. These estimates have been developed through discussions with a wide range of experts both inside and outside the utility industry, review of the trade and technical literature, and simulations and forecasts using several end-use models. The main results for efficient technologies that reduce electric usage are presented     

The origin of the band at 1462 cm−1 generally appearing upon desorption of pyridine from acidic solids. Steps towards a more comprehensive understanding

The pyridine adsorption-desorption method, followed by IR spectroscopy, is generally applied for acidity determination of solid catalysts. A peculiar band at 1462 cm^–1 was observed by several authors upon pyridine desorption at higher temperatures and was interpreted in various ways. A new complex between Lewis framework acid sites and pyridine is proposed and several evidences are reported.     

Automated derivation of time bounds in uniprocessor concurrentsystems

The successful development of complex real-time systems depends on analysis techniques that can accurately assess the timing properties of those systems. This paper describes a technique for deriving upper and lower bounds on the time that can elapse between two given events in an execution of a concurrent software system running on a single processor under arbitrary scheduling. The technique involves generating linear inequalities expressing conditions that must be satisfied by all executions of such a system and using integer programming methods to find appropriate solutions to the inequalities. The technique does not require construction of the state space of the system and its feasibility has been demonstrated by using an extended version of the constrained expression toolset to analyze the timing properties of some concurrent systems with very large state spaces